Claims:We claim,
1. A photosensitizer composition, said composition comprising
a therapeutically effective amount of phenothiazinium compound;
at least one phospholipid, or lysolipid or derivatives thereof;
micronized and/or nano metal particles, wherein said metal is at least one selected from a group consisting of gold and silver;
and a suitable excipient, and a suitable solvent.
2. The composition as claimed in claim 1, wherein said phenothiazinium compound is present in an amount in the range of 0.5 mg to 15.0 mg equivalent per ml of the total composition.
3. The composition as claimed in claim 1, wherein said phenothiazinium compound is present in an amount in the range of 0.1% (w/w) to 15% (w/w), of the total composition.
4. The composition as claimed in claim 1, wherein said phenothiazinium compound is at least one compound, or analog or derivative thereof, selected from a group consisting of methylene blue, rose bengal, toluidine blue O, brilliant crystal blue, neutral red, pyronin Y, new methylene blue, dimethyl methylene blue, dimethyl methylene blue, Azure A, Azure B and Azure C.
5. The composition as claimed in claim 1, wherein said phospholipid is selected from the group consisting of lyso-phosphatidylcholine, hydrogenated phosphatidyl choline, non-hydrogenated phosphatidylcholine, hydrogenated sunflower phosphatidylcholine, non-hydrogenated sunflower phosphatidylcholine, hydrogenated soybean phosphatidylcholine, non-hydrogenated soybean phosphatidylcholine, egg yolk phosphatidylcholine, and hydrogenated egg yolk phosphatidylcholine.
6. The composition as claimed in claim 1, wherein said phospholipid is present in an amount in the range of 0.1% to about 50% of the total composition in dosage.
7. The composition as claimed in claim 1, wherein said solvent is aqueous or lipophilic solvent, or mixtures thereof.
8. The composition as claimed in claim 1, wherein said solvent comprises diluted glycerin at a concentration in the range of 0.01% to 30% of the total weight of the composition.
9. The composition as claimed in claim 7, wherein said lipophilic solvent is at least one solvent selected from a group consisting of triglyceride, caprylic triglyceride, isopropyl myristate, isopropyl palmitate, ethyl linoleate, ethyl oleate ester of fatty acid, propylene glycol dicaprylate, propylene glycol dilaurate and propylene glycol fatty acid ester, or derivatives thereof.
10. The composition as claimed in claim 1, wherein zeta charge of said particles is in the range of -0.1 mV to -50 mV.
11. The composition as claimed in claim 1, wherein concentration of said metal particles in said composition is in the range of 2 to 400 ppm.
12. The composition as claimed in claim 1, further comprising at least one curcuminoid selected from a group consisting of diferuloylmethane, desmethoxycurcumin and bisdesmethoxycurcumin.
13. The composition as claimed in claim 12, wherein said lipophilic solvent is at a concentration in the range of 50 to 200 wt% of said photosensitizer.
14. The composition as claimed in claim 12, wherein said curcuminoid is diferuloylmethane in an amount in the range of 0.1% (w/w) to 15% (w/w), of the total composition.
15. The composition as claimed in claim 1, wherein said excipient is selected from a group consisting of Polyethylene glycol, glycine, mannitol, corn starch, gelatin, gum, and sucralose.
16. The composition as claimed in claim 1, wherein said excipient is present in an amount in the range of 0.2 to 70% of the total weight of the composition.
17. The composition as claimed in claim 15, wherein said polyethylene glycol is PEG 400, present in an amount in the range of 0.01% to 30% of the total weight of the composition.
18. The composition as claimed in claim 15, wherein said mannitol is present in an amount in the range of 10% to 60% of the total weight of the composition.
19. The composition as claimed in claim 15, wherein said glycine is present in an amount in the range of 0.5% to 10% of the total weight of the composition.
20. The composition as claimed in claim 15, wherein said starch is present in an amount in the range of 20% to 50% of the total weight of the composition.
21. The composition as claimed in claim 15, wherein said gelatin is at least one of fish or bovine gelatin, present in an amount in the range of 2% to 40% of the total weight of the composition.
22. The composition as claimed in claim 15, wherein said sucralose is present in an amount in the range of 0.1% to 5% of the total weight of the composition.
23. The composition as claimed in claim 1, wherein said composition is in at least one dosage from selected from the group consisting of solid, liquid and semisolid dosage form.
24. The composition as claimed in claim 1, wherein said composition is suitable for oromucosal administration.
25. The composition as claimed in claim 1, wherein said composition is a stabilized composition capable of remaining as a clear homogenous solution without precipitation for a minimum period of 24 hours.
26. The composition as claimed in claim 1, wherein said composition is having the ability to remain in a clear homogenous solution without precipitation of particles in aqueous phase, wherein dilution with an aqueous solvent is at a ratio of 1: 200.
27. The composition as claimed in claim 1, wherein said composition is a non-antibiotic antimicrobial composition.
28. The composition as claimed in claim 1, wherein said composition is a tablet.
29. The composition as claimed in claim 28, wherein said tablet is capable of disintegrating in oral cavity within a period in the range of 3 to 5 minutes.
30. A method for preparing the photosensitizer composition claimed in claim 1, said method comprising liquid-mixing said phenothiazinium compound with said solvent to obtain diluted phenothiazinium; adding said phospholipid, or lysolipid thereof, or derivatives thereof, and liquid mixing to obtain stabilized phenothiazinium mixture; adding metal nano and/or micro particles; sonicating to achieve dispersion; adding one or more suitable excipients and mixing to obtain a stabilized composition.
31. The method as claimed in claim 30, said method comprising liquid- mixing said diluted phenothiazinium with diluted glycerin.
32. The method as claimed in claim 30, said method further comprising adding at least one curcuminoid along with said metal particles to said stabilized phenothiazinium mixture and liquid-mixing.
33. The method as claimed in claim 30, wherein said mixing is performed to obtain a homogenous solution.
34. A method for treatment of microbial infections, said method comprising administering, to a subject in need thereof, a therapeutically effective amount of said photosensitizer composition claimed in claim 1.
35. The method as claimed in claim 34, said method comprising activating said photosensitizer composition by exposure to light energy of wavelength in the range of 610 to 670 nm.
36. The method as claimed in claim 34, wherein said subject is a patient having Coronavirus disease.
37. The method as claimed in claim 34, wherein said subject is having a antimicrobial resistant infection.
38. The method as claimed in claim 34, wherein said administering is performed by oromucosal route of administration.
39. An orally disintegrating tablet, comprising the composition claimed in claim 1.
40. The orally disintegrating tablet as claimed in claim 39, packaged in a clear blister pack. , Description:TECHNICAL FIELD
The embodiments disclosed herein relate to a photosensitizer composition having antimicrobial activity, more particularly to a photosensitizer composition capable of bypassing first pass metabolism. It also relates to a method of preparation of the photosensitizer composition.
BACKGROUND
Photodynamic therapy (PDT) includes a photosensitizer (PS) capable of photo activation by absorption of visible light to form reactive oxygen species (ROS). ROS are toxic to microbial cells.
Phenothiazinium compounds are an established class of antimicrobial PS that are amphipathic planar aromatic molecules having phototoxic efficiency against a broad range of microorganisms. It affects the cell’s metabolic cycle, wherein production of ATP and highly active singlet cytotoxic oxygen leads to microbial cell death. Its cytotoxic abilities upon photoactivation make it a suitable candidate in combating pathogenic microbes. Derivatives and analogs of phenothiaziniums such as Methylene blue (MB), 1-Octanol and 1,3-diphenylisobenzofuran (DPIBF), Rose Bengal (RB), new methylene blue (NMB) and dimethyl methylene blue (DMMB), Azure A (AA), azure C (AC), azure B (AB), toluidine blue O (TBO), brilliant crystal blue (BCB), pyronin Y (PYY) and neutral red (NR) have been recognized as clinically important molecules.
Methylene blue, a well-known phenothiazinium dye, is approved for clinical use and has an excellent safety profile. It has been significantly used in clinical treatment of chronic periodontitis and oral mucositis, and in light-induced disinfection of blood plasma to kill resistant bacterial strains and viruses. It is also used for treatment of methemoglobinemia, malaria, urinary tract infections, cyanide poisoning, carbon monoxide poisoning, pruritus Ani, and Alzheimer disease. Photoactivated MB is also extensively used to obtain blood product preparations free of viruses such as HIV. Cationic phenothiazine dyes possess a strong affinity to surface structures of viruses as well as viral DNA and RNA, thereby affecting the integrity of nucleic acids.
Diferuloylmethane is a non-antibiotic, natural polyphenolic PS having remarkable bactericidal properties. It has been shown to exhibit antioxidant, anti-inflammatory, antimicrobial, and anticarcinogenic activities. Light activation of Diferuloylmethane has also been shown to be effective against various bacteria & fungi such as Candida albicans.
The emergence of antibiotic resistant pathogens has necessitated an increased need for non-antibiotic antimicrobial approaches such as photodynamic therapy. Antimicrobial Resistance (AMR) has emerged as one of the most serious threat to public health in recent times. Phenothiazinium and Diferuloylmethane show potential to act as novel alternatives to conventional antibiotics. However, they undergo extensive first pass metabolism when administered orally for enteric absorption.
In attempts to overcome or compensate potential loss of active ingredient by first pass effect and ensure bioavailability, oral compositions of high dosage strength are administered. Topical and intra oral delivery of drugs may also alternatively be suitable for overcoming first pass effect. Moreover, achieving stable and effective compositions may be challenging, in some cases.
Diferuloylmethane suffers from low aqueous solubility and bioavailability and phenothiazinium, exhibits high solubility due to its hydrophilic nature, which may inhibit its passage into cells. Also due to its simple, planar structure it is highly aggregated, and this may reduce its ability to produce reactive oxygen species.

Therefore, there is an unmet and long-felt need to develop a stable, effective and safe non-antibiotic antimicrobial compositions having Phenothiazinium class of molecules.
 
OBJECTS
The principal object of the embodiments disclosed herein is to provide a photosensitizer composition comprising Phenothiazinium compounds.
A second object of the embodiments disclosed herein is to provide a photosensitizer composition capable of bypassing first pass metabolism.
Another object of the embodiments disclosed herein is to provide a photosensitizer composition having improved stability and bioavailability.
Another object of the embodiments disclosed herein is to provide an antimicrobial composition effective in reducing use of antibiotics and antimicrobial resistance (AMR).
An objective of the embodiments disclosed herein is to provide a phenothiazinium composition comprising a phospholipid, nano or micronized gold, nano or micronized silver, nano or micronized colloidal gold, or micronized colloid silver, suitable excipient and a suitable carrier.
Another object of the embodiments disclosed herein is to provide a phenothiazinium composition comprising at least one curcuminoid such as Diferuloylmethane.
Another object of the embodiments disclosed herein is to provide a non-antibiotic photosensitizer composition for the treatment of bacterial, fungal and/or viral infections as well as preventing the onset of bacterial and/or viral infections.
Another object of the embodiments disclosed herein is to provide effective and improved phenothiazinium composition.
Another object of the embodiments disclosed herein is to provide a Phenothiazinium composition for oromusocal administration.
Furthermore, object of the embodiments disclosed herein is to provide a phenothiazinium composition in a solution, tablet and gel form for oromucosal administration.
An object of the embodiments disclosed herein is to provide a composition and method for photodynamic therapy.
Yet another object of the embodiments disclosed herein is to provide a method for preparation of a photosensitizer composition.
An object of the embodiments disclosed herein is to provide a method for treatment of bacterial and/or viral infections.
These and other objects of the embodiments herein will be better appreciated and understood when considered in conjunction with the following description and the accompanying drawings. It should be understood, however, that the following descriptions, while indicating preferred embodiments and numerous specific details thereof, are given by way of illustration and not of limitation. Many changes and modifications may be made within the scope of the embodiments herein without departing from the spirit thereof, and the embodiments herein include all such modifications.
BRIEF DESCRIPTION OF FIGURES
The embodiments disclosed herein are illustrated in the accompanying drawings. The embodiments herein will be better understood from the following description with reference to the drawings, in which:
Fig. 1 is an illustration of the cellular mechanism of action of photosensitizer;
Fig. 2 are graphs depicting fluorescence intensity and rate of fluorescence of MB conjugated with gold nanoparticles;
Fig. 3 depicts a graph showing increment in fluorescence intensity by Phenothiazinium category molecule;
Fig. 4 are images from TEM, SEM, and Confocal Laser Scanning Microscopy (CLSM) analysis showing photo-cytotoxicity by phenothiazinium category molecule;
Fig. 5 depicts TEM image of Methylene blue-liposomes and a graph showing Dynamic light scattering (DLS) measurement of MB-liposomes;
Fig. 6 is UV-Vis’s spectra of free MB, MB-liposomes, and MB-liposomes with Nano Gold & silver 4.5mcg & 6.5mcg respectively, and a graph depicting stability of composition - hydrodynamic diameter of MB-liposomes over 14 days;
Fig. 7 are TEM images of Phenothiazinium category molecule and a graph showing nano particle size;
Fig. 8 are images depicting liposome entrapped Phenothiazinium category molecule, Phenothiazinium category molecule - liposome after removal of coating, and enzymatic treatment of Phenothiazinium category molecule – liposome; and a graph depicting particle size distribution before and after treatment; and zeta potential of various Phenothiazinium category molecule;
Fig. 9 depicts graph showing 24-h cell viability (by MTT assay) of free MB and MB-liposomes and Distilled Water (DI) as control at different concentrations with dark treatment and photodynamic therapy (PDT) treatment, and the images depict free MB and MB-liposomes at 8µm concentration and Distilled Water (DI) with dark treatment and photodynamic therapy (PDT) treatment;
Fig. 10 are SEM images of Curcumin nanoparticles and silver & gold nanoparticles;
Fig. 11 are SEM images of colloidal gold nanorods;
Fig. 12 are images depicting Phenothiazinium category molecule, Phenothiazinium category molecule liposomal form, oxidation rate, and Phenothiazinium category molecule liposomal form after sonification;
Fig. 13 is a pictorial representation of blue light excitation of Liposomal - MB and red light excitation of Liposomal – MB respectively;
Fig. 14 is a graph depicting X ray diffraction pattern of Colloidal silver nanoparticles;
Fig. 15 is a graph showing X ray diffraction pattern of pure curcumin;
Fig. 16 depicts ESI mass spectrum of methylene blue before and after overnight irradiation respectively;
Fig. 17 is a graph showing nano silver mass spectrometry pattern;
Fig. 18 depicts Mass spectra Pattern of Curcumin; wherein 18(a) is mass spectra of curcumin; 18(b) is mass spectra of hydroxylated curcumin, while 18(c) is mass spectra of daughter ion of curcumin;
Fig. 19 are graphs showing absorption spectra of colloidal gold ion of 5 nm and 20 nm and colloidal gold with low molecular complex respectively;
Fig. 20 is a schematic overview of photo inactivation of multidrug resistant microbes by monomeric methylene blue conjugated gold nanoparticles;
Fig. 21 is a schematic representation depicting tailoring photosensitive ROS for advance photodynamic therapy; and Jablonski diagram showing the photo chemical mechanism;
Fig. 22 is a schematic representation of Tissue penetration depths of various wavelengths;
Fig. 23 is a graph with the central image shows photospectrometric data measured from penetration through a human hand in vivo; and
Fig. 24 is a schematic representation of general action mechanism of photodynamic applications on viruses.
 
DETAILED DESCRIPTION
The embodiments herein and the various features and advantageous details thereof are explained more fully with reference to the non-limiting embodiments that are illustrated in the accompanying drawings and detailed in the following description. Descriptions of well-known features and processing techniques are omitted so as to not unnecessarily obscure the embodiments herein. The examples used herein are intended merely to facilitate an understanding of ways in which the embodiments herein may be practiced and to further enable those of skill in the art to practice the embodiments herein. Accordingly, the examples should not be construed as limiting the scope of the embodiments herein.
The embodiments herein achieve compositions comprising photosensitizers, particularly phenothiazinium compounds. The disclosed photosensitizer compositions are intended for therapeutic use which are capable of bypassing first pass metabolism. The embodiments of the composition are capable of overcoming potential loss or reduction in active ingredients caused due to first pass effect or pre-systemic metabolism. The embodiments herein are such that it is capable of rapid and effective entry into systemic circulation after administration. Further, embodiments herein also include effective compositions having optimum solubility of active ingredient. Accordingly, embodiments herein include a composition having improved bioavailability and stability. Further, embodiments herein include non-antibiotic antimicrobial compositions. The embodiments herein are capable of reducing use or intake of antibiotic for treating microbial infections. It further also contributes towards alleviating antimicrobial resistance (AMR). Accordingly, embodiments herein include antimicrobial compositions capable of overcoming or reducing antimicrobial resistance. The compositions disclosed herein are useful for treating or preventing microbial infections including bacterial and viral infections, and inactivating microbes in blood and other biological fluids. It has also been observed that the embodiments of the disclosed compositions are effective in treatment and management of infections by pathogenic microbes such as bacteria, virus, etc. Accordingly, disclosed herein are embodiments of a method for treatment of microbial infections. Embodiments herein disclose composition and method for photodynamic treatment of microbial infections.
Composition
The disclosed embodiments herein include compositions having a combination of selected components capable of improving drug solubility, permeability across biological membranes and absorption. The embodiments herein achieve a composition for intra oral or oromucosal administration or delivery of active pharmaceutical ingredients, particularly photosensitizers. The composition, according to embodiments herein, are such that they are capable of bypassing or overcoming first pass metabolism. The term “first pass effect” or “first pass metabolism”, as used herein refers to its generally accepted meaning. It is usually observed in orally administered drugs passing the GI tract for absorption and distribution, potentially leading to reduced bioavailability. The embodiments herein, include compositions having optimum stability, permeability and solubility having improved bioavailability. In an embodiment, the composition includes at least one photosensitizer. In another embodiment, the composition is a photosensitizer composition for oromucosal administration. The term “intraoral administration” or “oromucosal administration”, used interchangeably herein refers to delivery to the oral cavity. Examples of oromucosal administration include, but not limited to, delivery through buccal, sublingual and gingival routes. Further, the disclosed composition may also be suitable for other routes of administration such as transdermal, intranasal, ocular and intravenous routes. In other embodiment, the composition is a photosensitizer composition for at least one of transdermal, intranasal, ocular and/or intravenous routes of administration.
In some embodiments, the composition includes liposome structures encapsulating one or more photosensitizers. Liposome, according to embodiments herein, refer to its generally known meaning which includes closed structures comprising one or more outer lipid layer surrounding an internal aqueous space. In an embodiments, the composition is a liposomal composition.
In another embodiment, the composition includes at least one photosensitizer, phospholipid, one or more suitable excipients, suitable solvent and suitable carrier. In another embodiment, the composition includes at least one photosensitizer, phospholipid, metal nanoparticles, one or more excipients, suitable solvent and suitable carrier.
Photosensitizer
The disclosed embodiments herein include at least one photosensitizer. The term “photosensitizer”, as used herein refer to any compound capable of photoactivation, particularly for generating cytotoxic species such as reactive oxygen species (ROS). It includes photosensitizing agents. It further includes salts, or prodrug, or analogs, or derivatives of such photosensitizers. Various photosensitizers are generally known and may be used in various embodiments herein. Examples of photosensitizers include, but is not limited to, prophyrins; dyes such as phenothiazinium, phenodiazinium, phenooxaziniums; chlorophyll; chlorins; bacteriochlorins; phenothiaziniums; prophycenes; and other natural occurring photosensitizing agents, or mixtures thereof. In some embodiments the photosensitizer may be functional using molecules such as functional groups, ligands, etc. The composition may include one or more photosensitizers. In an embodiment, the photosensitizer is a phenothiazinium compound. In another embodiment, the photosensitizer is a naturally occurring compound such as diferuloylmethane. The embodiments of the composition disclosed herein may include one or more photosensitizers in suitable amounts.
Phenothiazinium
In an embodiment, the composition includes phenothiazinium. According to embodiments herein, phenothiaziniums or phenothiazinium compounds, used interchangeably, include phenothiazinium or phenothiazinium-like molecules including, but not limited to, their salts, analogs, prodrugs, conjugates, and/or derivatives. Examples of phenothiaziniums include, but is not limited to, methylene blue, rose bengal, toluidine blue O, brilliant crystal blue, neutral red, pyronin Y, new methylene blue, dimethyl methylene blue, dimethyl methylene blue, Azure A, Azure B and Azure C. In an embodiment, the composition includes methylene blue. Further in an embodiment, the composition includes rose bengal. Further in an embodiment, the composition includes toluidine blue. Further in an embodiment, the composition includes brilliant crystal blue. In another embodiment, the composition includes neutral red. Further in an embodiment, the composition includes pyronin Y. In yet another embodiment, the composition includes new methylene blue. Further in an embodiment, the composition includes dimethyl methylene blue. Further in an embodiment, the composition includes Azure A. In another embodiment, the composition includes Azure B. Further in an embodiment, the composition includes Azure C.
The photosensitizer, in various embodiments herein, may be present in a therapeutically effective amount, in the composition. In an embodiment, the composition comprises phenothiazinium compounds in an amount ranging from 0.5 mg equivalent to about 15.0 mg equivalent.
In an embodiment, the composition comprises phenothiazinium compounds in about 0.5 mg equivalent, 1.0 mg equivalent, 1.5 mg equivalent, 2.0 mg equivalent, 2.5 mg equivalent, 3.0 mg equivalent, 3.5 mg equivalent, 4.0 mg equivalent, 4.5 mg equivalent, 5.0 mg equivalent, 5.5 mg equivalent, 6.0 mg equivalent, 6.5 mg equivalent, 7.0 mg equivalent, 7.5 mg equivalent, 8.0 mg equivalent, 8.5 mg equivalent, 9.0 mg equivalent, 9.5 mg equivalent, 10.0 mg equivalent, 10.5 mg equivalent, 11.0 mg equivalent, 11.5 mg equivalent, 12.0 mg equivalent, 12.5 mg equivalent, 13.0 mg equivalent, 13.5 mg equivalent, 14.0 mg equivalent, 14.5 mg equivalent, or 15.0 mg equivalent, of the total weight.
In another embodiment disclosed herein, the composition comprises phenothiazinium or a derivative thereof in an amount ranging from 0.01% to 15% of the total composition. Further in yet another embodiment disclosed herein, the composition comprises Phenothiazinium or derivatives thereof, a hydrate or a solvate thereof; about 5% (w/w) to about 20% (w/w) of the total composition.
In an embodiment, the composition comprises about 0.01%, 0.02%, 0.03%, 0.04%, 0.05%, 0.06%, 0.07%, 0.08%, 0.09%, 0.1%, 0.25%, 0.5%, 0.75%, 1.0%, 1.25%, 1.5%, 1.75%, 2.0%, 2.25%, 2.5%, 2.75%, 3.0%, 3.25%, 3.5%, 3.75%, 4.0%, 4.25%, 4.5%, 4.75%, 5.0%, 5.25%, 5.5%, 5.75%, 6.0%, 6.25%, 6.5%, 6.75%, 7.0% , 7.25%, 7.5%, 7.75%, 8.0%, 8.25%, 8.5%, 8.75%, 9.0%, 9.25%, 9.5%, 9.75%, 10.0%, 10.25%, 10.5%, 10.75%, 11.0%, 11.25%, 11.50% , 11.75% , 12.0%, 12.25%, 12.50%, 12.75%, 13.0%, 13.25%, 13.50%, 13.75%, 14.0%, 14.25%, 4.50%, 14.75% or 15.0%, of the total composition.
Curcuminoid
In an embodiment, the composition further includes curcuminoid. The term "curcuminoid”, as used herein, refers to biologically active compounds in the plant Curcuma longa. It includes curcumin and non-curcumin compounds such as desmethoxycurcumin, bisdesmethoxycurcumin, etc. It also includes derivative, conjugates, analogs, etc. of curcuminoids. In an embodiment, the composition includes curcumin, also referred to herein as Diferuloylmethane. The curcuminoids may be included in any suitable form for eg: as extracts such as aqueous, alco-aqueous or alcoholic extract; isolates; or chemically synthesized compounds. In an embodiment, diferuloylmethane is an extract of turmeric (Curcuma Longa plant) in the form of viscous oily fluids, pasty semisolids or hard amorphous solids, and which comprise in varying concentrations, both curcuminoids and essential volatile oil, wherein the volatile oil comprises a mixture of non-curcuminoids in varying concentrations.
In an embodiment, the composition comprises curcuminoid in an amount ranging from 0.5 mg equivalent to 15.0 mg equivalent. In an embodiment, the composition comprises diferuloylmethane in an amount in the range of 0.1% (w/w) to 15% (w/w), of the total composition. In an embodiment, the composition comprises Diferuloylmethane in about 0.5 mg equivalent, 1.0 mg equivalent, 1.5 mg equivalent, 2.0 mg equivalent, 2.5 mg equivalent, 3.0 mg equivalent, 3.5 mg equivalent, 4.0 mg equivalent, 4.5 mg equivalent, 5.0 mg equivalent, 5.5 mg equivalent, 6.0 mg equivalent, 6.5 mg equivalent, 7.0 mg equivalent, 7.5 mg equivalent, 8.0 mg equivalent, 8.5 mg equivalent, 9.0 mg equivalent, 9.5 mg equivalent, 10.0 mg equivalent, 10.5 mg equivalent, 11.0 mg equivalent, 11.5 mg equivalent, 12.0 mg equivalent, 12.5 mg equivalent, 13.0 mg equivalent, 13.5 mg equivalent, 14.0 mg equivalent, 14.5 mg equivalent, or 15.0 mg equivalent, of the total weight.
Phospholipids
In an embodiment as disclosed herein, the composition further includes phospholipids. Phospholipids according to embodiments herein, includes, but is not limited to, phosphatidylcholine, hydrogenated phosphatidylcholine, non-hydrogenated phosphatidylcholine, hydrogenated sunflower phosphatidylcholine, non-hydrogenated sunflower phosphatidylcholine, hydrogenated soybean phosphatidylcholine, non-hydrogenated soybean phosphatidylcholine, egg yolk phosphatidylcholine, and hydrogenated egg yolk phosphatidylcholine. It further includes any lysolipids, lyso-phospholipids, conjugates or derivative of phospholipids.
In an embodiment, the composition includes at least one phospholipid selected from a group consisting of phosphatidylcholine and lyso-phosphatidylcholine. Further in an embodiment disclosed herein, the phosphatidylcholine used in the composition contains a minimum specification of 75% to 100%, as detected by HPLC-RI method. Further in an embodiment disclosed herein, the lyso-phosphatidylcholine used in the composition bypassing first phase metabolism contains a minimum specification of 0.5 to 10%, as detected by HPLC-PLH method.
In an embodiment, the composition comprises hydrogenated phosphatidylcholine. Further in another embodiment, the composition comprises non-hydrogenated phosphatidylcholine. Further in an embodiment, the composition comprises a phosphatidylcholine that is hydrogenated sunflower phosphatidylcholine. Further in an embodiment, the composition comprises a phosphatidylcholine that is non-hydrogenated sunflower phosphatidylcholine. Further in an embodiment, the composition comprises a phosphatidylcholine that is hydrogenated soybean phosphatidylcholine. In another embodiment, the composition comprises a phosphatidylcholine that is non-hydrogenated soybean phosphatidylcholine. Further in an embodiment, the composition comprises a phosphatidylcholine that is egg yolk phosphatidylcholine. In yet another embodiment, the composition comprises a phosphatidylcholine that is hydrogenated egg yolk phosphatidylcholine. The amount of phospholipids may be vary, and is preferably in the range of 0.1% to 50% of the total lipid composition. The amount of phosphatidylcholine may vary and is preferably in the range of 3% to 70% of the total phospholipids in the composition. The amount of lyso-phosphatidylcholine may be vary and is preferably in the range of 0% to 25% of the total phospholipids in the composition.
The amount of phosphatidylcholine, in some embodiments is about 5%, 7.5%, 10%, 15%, 20%, 22%, 25%, 27%, 30%, 32%, 35%, 37%, 40%, 42%, 45%, 47%, 49%, 49.5%, or 50% by weight of the total amount of phospholipids in the composition.
In an embodiment, the composition comprises phosphatidylcholine in an amount ranging from 0.1% to 50% of the total weight of the composition. The amount of phosphatidylcholine may be 0.1%, 0.5%, 1.0%, 1.5%, 2.0%, 2.5%, 3.0%, 3.5%, 4.0%, 4.5%, 5.0%, 6.0%, 7.0%, 8.0%, 9.0, 10.0%, 12.5%, 15.0%, 17.5%, 20.0%, 22.5%, 25.0%, 27.5%, 30.0%, 32.5%, 35.0%, 37.5%, 40.0%, 42.5%, 45.0%, 47.5% or 50.0% of the total weight of the composition.
In an embodiment, the composition comprises of phosphatidylcholine in an amount ranging from 1 mg to 50 mg. The amount of phosphatidylcholine may be 1 mg, 2 mg, 3 mg, 4 mg, 5 mg, 6 mg, 7mg, 8 mg, 9 mg, 10 mg, 11 mg, 12 mg, 13 mg, 14 mg, 15 mg, 16 mg, 17 mg, 18 mg, 19 mg, 20 mg, 21 mg, 22 mg, 23 mg, 24 mg, 25 mg, 26 mg, 27 mg, 28 mg, 29 mg, 30 mg, 31 mg, 32 mg, 33 mg, 34 mg, 35 mg, 36 mg, 37 mg, 38 mg, 39 mg, 40 mg, 41 mg, 42 mg, 43 mg, 44 mg, 45 mg, 46 mg, 47 mg, 48 mg, 49 mg, or 50 mg in the composition.
In an embodiment, the composition comprises of lyso-phosphatidylcholine in an amount ranging from 0% by weight to about 25% by weight of the total amount of phospholipids in the composition. The amount of lyso-phosphatidylcholine may be 0%, 0.5%, 1.0%, 1.5%, 2.0%, 2.5%, 3.0%, 3.5%, 4.0%, 4.5%, 5.0%, 7.5%, 10%, 12.5%, 15%, 17.5%, 20%, 22.5% or 25% by weight of the total amount of phospholipids in the composition.
Nano particles
In an embodiment, the composition further includes metal particles. Examples of metal include but is not limited to gold and silver. The metal particles, according to embodiments herein, may be in the form of nano and/ or micro or micronized particles. Further, the nanoparticles may be stabilized by one of more emulsifiers, oils, surfactants, etc. The particle size of the metal particles, according to embodiments herein, are nano and/or micro or micronized particles which, as used herein refers to particles in the nano meter and micro meter range. The term “nano” or “nanoparticle”, as used herein is intended to cover all such particles having nano meter and micro meter range particles. It may range between 1 nm to 1 µm, preferably 0.1 µm to 0.5 µm or 10 nm to 100 nm. Preferably, nanometer refers to particles in the size range of 1 to 100 nm, or 10 to 100 nm. Preferably, micronized refers to particles in the size range of 100 to 500 nm, or 100 to 200 nm or 200 to 400 nm. Further, the metal particles may be present or introduced in the composition in any suitable form or generally accepted form, for e.g.: colloidal, suspended, dispersed, unaggregated, etc. Colloidal forms, in some embodiments preferably refers to metal particles suspended in solution or liquid than being added to a solution or suspension, or a gel or tablet.
In an embodiment, the metal particles are present in unaggregated forms. In an embodiment, the metal particles are in colloidal form. In an embodiment, the composition includes gold nanoparticles. In an embodiment, the composition includes silver nanoparticles. In an embodiment, the composition includes gold microparticles. In another embodiment, the composition includes silver microparticles. In an embodiment, the composition includes nano and/or micro particles of gold and silver.
The metal nanoparticles, according to embodiments herein, have optimum Zeta potential. Zeta potential is generally known as the potential difference between the dispersion medium and the stationary layer of fluid attached to the particle. The zeta potential charge of metal particles, according to embodiments herein may range from -1.0 mV to -40 mV. In an embodiment, the composition comprises metal particles having a zeta potential of about -1.0mV, -1.5mV, -2.0mV, -2.5mV, -3.0mV, -3.5mV, -4.0mV, -4.5mV, -5.0mV, -5.5mV, -6.0mV, -6.5mV, -7.0mV, -7.5mV, -8.0mV, -8.5mV, -9.0mV, -9.5mV, -10.0mV, -10.5mV, -11.0mV, -11.5mV, -12.0mV, -12.5mV, -13.0mV, -13.5mV, -14.0mV, -14.5mV, -15.0mV, -15.5mV, -16.0mV, -16.5mV, -17.0mV, -17.5mV, -18.0mV, -18.5mV, -19.0mV, -19.5mV, -20.0mV, -20.5mV, -21.0mV, -21.5mV, -22.0mV, -22.5mV, -23.0mV, -23.5mV, -24.0mV, -24.5mV, -25.0mV, -25.5mV, -26.0mV, -26.5mV, -27.0mV, -27.5mV, -28.0mV, -28.5mV, -29.0mV, -29.5mV, -30.0mV, -30.5mV, -31.0mV, -31.5mV, -32.0mV, -32.5mV, -33.0mV, -33.5mV, -34.0mV, -34.5mV, -35.0mV, -35.5mV, -36.0mV, -36.5mV, -37.0mV, -37.5mV, -38.0mV, -38.5mV, -39.0mV, -39.5mV or -40.0mV.
The metal nanoparticles, according to embodiments herein, may be included in the composition in an amount suitable to stabilize the composition. The suitable amount may range from 2 ppm to 400 ppm, or about 0.01 mcg to 60 mcg, of the total composition. In an embodiment, the composition comprises metal particles in the range of 0.5 ppm to 400 ppm, or about 5 ppm to 200 ppm. In an embodiment, the amount of nano or micronized gold and/or silver particles is about 5.0 ppm, 7.5 ppm, 10.0 ppm, 12.5 ppm, 15.0 ppm, 17.5 ppm, 20.0 ppm, 22.5 ppm, 25.0 ppm, 27.5 ppm, about 30 ppm, 32.5 ppm, 35.0 ppm, 37.5 ppm, 40.0 ppm, 42.5 ppm, 45.0 ppm, 47.5 ppm, 50 ppm, 52.5 ppm, 55 ppm, 57.5 ppm, 60 ppm, 62.5 ppm, 65 ppm, 67.5 ppm, 70 ppm, 72.5 ppm, 75 ppm, 77.5 ppm, 80 ppm, 82.5 ppm, 85 ppm, 87.5 ppm, 90 ppm, 92.5 ppm, 95 ppm, 97.5 ppm, 100.0 ppm, 102.5 ppm, 105.0 ppm, 107.5 ppm, 110.0 ppm, 112.5 ppm, 115.0 ppm, 117.5 ppm, 120.0 ppm, 122.5 ppm, 125.0 ppm, 127.5 ppm, 130.0 ppm, 132.5 ppm, 135.0 ppm, 137.5 ppm, 140.0 ppm, 142.5 ppm, 145.0 ppm, 147.5 ppm, 150.0 ppm, 152.5 ppm, 155.0 ppm, 157.5 ppm, 160.0 ppm, 162.5 ppm, 165.0 ppm, 167.5 ppm, 170.0 ppm, 172.5 ppm, 175.0 ppm, 172.5 ppm, 175.0 ppm, 177.5 ppm, 180.0 ppm, 182.5 ppm, 185.0 ppm, 187.5 ppm, 190.0 ppm, 192.5 ppm, 195.5 ppm, 197.5 ppm or 200.0 ppm, in the composition.
In another embodiment, the amount of nano and/or micronized colloidal, gold and/or silver particles is about 5.0 ppm, 7.5 ppm, 10.0 ppm, 12.5 ppm, 15.0 ppm, 17.5 ppm, 20.0 ppm, 22.5 ppm, about 25.0 ppm, 27.5 ppm, 30 ppm, 32.5 ppm, 35.0 ppm, 37.5 ppm, 40.0 ppm, 42.5 ppm, 45.0 ppm, 47.5 ppm, 50 ppm, 52.5 ppm, 55 ppm, 57.5 ppm, 60 ppm, about 62.5 ppm, 65 ppm, 67.5 ppm, 70 ppm, 72.5 ppm, 75 ppm, 77.5 ppm, about 80 ppm, about 82.5 ppm, 85 ppm, 87.5 ppm, 90 ppm, 92.5 ppm, 95 ppm, 97.5 ppm, 100.0 ppm, 102.5 ppm, 105.0 ppm, 107.5 ppm, 110.0 ppm, 112.5 ppm, 115.0 ppm, 117.5 ppm, 120.0 ppm, 122.5 ppm, 125.0 ppm, 127.5 ppm, 130.0 ppm, 132.5 ppm, 135.0 ppm, 137.5 ppm, 140.0 ppm, 142.5 ppm, 145.0 ppm, 147.5 ppm, 150.0 ppm, 152.5 ppm, 155.0 ppm, 157.5 ppm, 160.0 ppm, 162.5 ppm, 165.0 ppm, 167.5 ppm, 170.0 ppm, 172.5 ppm, 175.0 ppm, 172.5 ppm, 175.0 ppm, 177.5 ppm, 180.0 ppm, 182.5 ppm, 185.0 ppm, 187.5 ppm, 190.0 ppm, 192.5 ppm, 195.5 ppm, 197.5 ppm, 200.0 ppm, 202.5 ppm, 205.0 ppm, 207.5 ppm, 210.0 ppm, 212.5 ppm, 215.0 ppm, 217.5 ppm, 220.0 ppm, 222.5 ppm, 225.0 ppm, 227.5 ppm, 230.0 ppm, 232.5 ppm, 235.0 ppm, 237.5 ppm, 240.0 ppm, 242.5 ppm, 245.0 ppm, 247.5 ppm, 250.0 ppm, 252.5 ppm, 255.0 ppm, 257.5 ppm, 260.0 ppm, 262.5 ppm, 265.0 ppm, 267.5 ppm, 270.0 ppm, 272.5 ppm, 275.0 ppm, 272.5 ppm, 275.0 ppm, 277.5 ppm, 280.0 ppm, 282.5 ppm, 285.0 ppm, about 287.5 ppm, 290.0 ppm, 292.5 ppm, 295.5 ppm, 297.5 ppm, 300.0 ppm, 302.5 ppm, 305.0 ppm, 307.5 ppm, 310.0 ppm, 312.5 ppm, 315.0 ppm, 317.5 ppm, 320.0 ppm, 322.5 ppm, 325.0 ppm, 327.5 ppm, 330.0 ppm, 332.5 ppm, 335.0 ppm, 337.5 ppm, about 340.0 ppm, 342.5 ppm, 345.0 ppm, 347.5 ppm, 350.0 ppm, 352.5 ppm, 355.0 ppm, 357.5 ppm, 360.0 ppm, 362.5 ppm, 365.0 ppm, 367.5 ppm, 370.0 ppm, 372.5 ppm, 375.0 ppm, 372.5 ppm, 375.0 ppm, 377.5 ppm, 380.0 ppm, 382.5 ppm, 385.0 ppm, 387.5 ppm, 390.0 ppm, 392.5 ppm, 395.0 ppm, 397.5 ppm, or 400.0 ppm, in the composition.
In another embodiment, the amount of nano and/or micronized colloidal, gold and/or silver particles is about 0.1 mcg, 0.5 mcg, 1.0 mcg, 1.5 mcg, 2.0 mcg, 2.5 mcg, 3.0 mcg, 3.5 mcg, 4.0 mcg, 4.5 mcg, 5.0 mcg, 5.5 mcg, 6.0 mcg, 6.5 mcg, 7.0 mcg, 7.5 mcg, 8.0 mcg, 8.5 mcg, 9.0 mcg, 9.5 mcg, 10.0 mcg, 10.5 mcg, 11.0 mcg, 11.5 mcg, 12.0 mcg, 12.5 mcg, 13.0 mcg, 13.5 mcg, 14.0 mcg, 14.5 mcg, 15.0 mcg, 15.5 mcg, 16.0 mcg, 16.5 mcg, 17.0 mcg, 17.5 mcg, 18.0 mcg, 18.5 mcg, 19.0 mcg, 19.5 mcg, 20.0 mcg, 20.5 mcg, 22.0 mcg, 22.5 mcg, 23.0 mcg, 23.5 mcg, 24.0 mcg, 24.5 mcg, 25.0 mcg, 27.5 mcg, 30.0 mcg, 32.5 mcg, 35.0 mcg, 37.5 mcg, 40.0 mcg, 42.5 mcg, 45.0 mcg, 47.5 mcg, or 50.0, in the composition.
In an embodiment disclosed herein, the composition comprises nano or micronized gold or nano or micronized colloidal gold in an amount ranging from 0.1 mcg to 50 mcg. The amount of nano or micronized gold or nano or micronized colloidal gold may be 0.1 mcg, 0.5 mcg, 1.0 mcg, 1.5 mcg, 2.0 mcg, 2.5 mcg, 3.0 mcg, 3.5 mcg, 4.0 mcg, 4.5 mcg, 5.0 mcg, 5.5 mcg, 6.0 mcg, 6.5 mcg, 7.0 mcg, 7.5 mcg, 8.0 mcg, 8.5 mcg, 9.0 mcg, 9.5 mcg, 10.0 mcg, 10.5 mcg, 11.0 mcg, 11.5 mcg, 12.0 mcg, 12.5 mcg, 13.0 mcg, 13.5 mcg, 14.0 mcg, 14.5 mcg, 15.0 mcg, 15.5 mcg, 16.0 mcg, 16.5 mcg, 17.0 mcg, 17.5 mcg, 18.0 mcg, 18.5 mcg, 19.0 mcg, 19.5 mcg, 20.0 mcg, 20.5 mcg, 22.0 mcg, 22.5 mcg, 23.0 mcg, 23.5 mcg, 24.0 mcg, 24.5 mcg, 25.0 mcg, 27.5 mcg, 30.0 mcg, 32.5 mcg, 35.0 mcg, 37.5 mcg, 40.0 mcg, 42.5 mcg, 45.0 mcg, 47.5 mcg, or 50.0 mcg in the composition.
In an embodiment disclosed herein, the composition comprises nano or micronized gold in solution and is present in an amount ranging from 5 ppm to 200 ppm. The amount of nano or micronized gold may be 5.0 ppm, 7.5 ppm, 10.0 ppm, 12.5 ppm, 15.0 ppm, 17.5 ppm, 20.0 ppm, 22.5 ppm, 25.0 ppm, 27.5 ppm, about 30 ppm, 32.5 ppm, 35.0 ppm, 37.5 ppm, 40.0 ppm, 42.5 ppm, 45.0 ppm, 47.5 ppm, 50 ppm, 52.5 ppm, 55 ppm, 57.5 ppm, 60 ppm, 62.5 ppm, 65 ppm, 67.5 ppm, 70 ppm, 72.5 ppm, 75 ppm, 77.5 ppm, 80 ppm, 82.5 ppm, 85 ppm, 87.5 ppm, 90 ppm, 92.5 ppm, 95 ppm, 97.5 ppm, 100.0 ppm, 102.5 ppm, 105.0 ppm, 107.5 ppm, 110.0 ppm, 112.5 ppm, 115.0 ppm, 117.5 ppm, 120.0 ppm, 122.5 ppm, 125.0 ppm, 127.5 ppm, 130.0 ppm, 132.5 ppm, 135.0 ppm, 137.5 ppm, 140.0 ppm, 142.5 ppm, 145.0 ppm, 147.5 ppm, 150.0 ppm, 152.5 ppm, 155.0 ppm, 157.5 ppm, 160.0 ppm, 162.5 ppm, 165.0 ppm, 167.5 ppm, 170.0 ppm, 172.5 ppm, 175.0 ppm, 172.5 ppm, 175.0 ppm, 177.5 ppm, 180.0 ppm, 182.5 ppm, 185.0 ppm, 187.5 ppm, 190.0 ppm, 192.5 ppm, 195.5 ppm, 197.5 ppm or 200.0 ppm in the composition.
In an embodiment disclosed herein, the composition comprises nano or micronized colloidal gold in solution and is present in an amount ranging from 5 ppm to 400 ppm. The amount of nano or micronized colloidal gold may be 5.0 ppm, 7.5 ppm, 10.0 ppm, 12.5 ppm, 15.0 ppm, 17.5 ppm, 20.0 ppm, 22.5 ppm, about 25.0 ppm, 27.5 ppm, 30 ppm, 32.5 ppm, 35.0 ppm, 37.5 ppm, 40.0 ppm, 42.5 ppm, 45.0 ppm, 47.5 ppm, 50 ppm, 52.5 ppm, 55 ppm, 57.5 ppm, 60 ppm, about 62.5 ppm, 65 ppm, 67.5 ppm, 70 ppm, 72.5 ppm, 75 ppm, 77.5 ppm, about 80 ppm, about 82.5 ppm, 85 ppm, 87.5 ppm, 90 ppm, 92.5 ppm, 95 ppm, 97.5 ppm, 100.0 ppm, 102.5 ppm, 105.0 ppm, 107.5 ppm, 110.0 ppm, 112.5 ppm, 115.0 ppm, 117.5 ppm, 120.0 ppm, 122.5 ppm, 125.0 ppm, 127.5 ppm, 130.0 ppm, 132.5 ppm, 135.0 ppm, 137.5 ppm, 140.0 ppm, 142.5 ppm, 145.0 ppm, 147.5 ppm, 150.0 ppm, 152.5 ppm, 155.0 ppm, 157.5 ppm, 160.0 ppm, 162.5 ppm, 165.0 ppm, 167.5 ppm, 170.0 ppm, 172.5 ppm, 175.0 ppm, 172.5 ppm, 175.0 ppm, 177.5 ppm, 180.0 ppm, 182.5 ppm, 185.0 ppm, 187.5 ppm, 190.0 ppm, 192.5 ppm, 195.5 ppm, 197.5 ppm, 200.0 ppm, 202.5 ppm, 205.0 ppm, 207.5 ppm, 210.0 ppm, 212.5 ppm, 215.0 ppm, 217.5 ppm, 220.0 ppm, 222.5 ppm, 225.0 ppm, 227.5 ppm, 230.0 ppm, 232.5 ppm, 235.0 ppm, 237.5 ppm, 240.0 ppm, 242.5 ppm, 245.0 ppm, 247.5 ppm, 250.0 ppm, 252.5 ppm, 255.0 ppm, 257.5 ppm, 260.0 ppm, 262.5 ppm, 265.0 ppm, 267.5 ppm, 270.0 ppm, 272.5 ppm, 275.0 ppm, 272.5 ppm, 275.0 ppm, 277.5 ppm, 280.0 ppm, 282.5 ppm, 285.0 ppm, 287.5 ppm, 290.0 ppm, 292.5 ppm, 295.5 ppm, 297.5 ppm, 300.0 ppm, 302.5 ppm, 305.0 ppm, 307.5 ppm, 310.0 ppm, 312.5 ppm, 315.0 ppm, 317.5 ppm, 320.0 ppm, 322.5 ppm, 325.0 ppm, 327.5 ppm, 330.0 ppm, 332.5 ppm, about 335.0 ppm, 337.5 ppm, 340.0 ppm, 342.5 ppm, 345.0 ppm, 347.5 ppm, 350.0 ppm, 352.5 ppm, 355.0 ppm, 357.5 ppm, 360.0 ppm, 362.5 ppm, 365.0 ppm, 367.5 ppm, 370.0 ppm, 372.5 ppm, 375.0 ppm, 372.5 ppm, 375.0 ppm, 377.5 ppm, 380.0 ppm, 382.5 ppm, 385.0 ppm, 387.5 ppm, 390.0 ppm, 392.5 ppm, 395.0 ppm, 397.5 ppm, or 400.0 ppm in the composition.
In an embodiment disclosed herein, the composition comprises nano or micronized gold or nano or micronized colloidal gold with a particle size ranging from 1 nm to 325 nm. The particle size of nano or micronized gold or nano or micronized colloidal gold may be 1 nm, 2 nm, 3 nm, 4 nm, 5 nm, 6 nm, 7 nm, 8 nm, 9 nm, 10, nm, 12.5 nm, 15.0 nm, 17.5 nm, 20.0 nm, 22.5 nm, 25.0 nm, 27.5 nm, 30 nm, 32.5 nm, 35 nm, 37.5 nm, 40.0 nm, 42.5 nm, 45.0 nm, 47.5 nm, 50.0 nm, 52.5 nm, 55.0 nm, 57.5 nm, 60.0 nm, 62.5 nm, 65.0 nm, 67.5 nm, 70.0 nm, 72.5 nm, 75.0 nm, 77.5 nm, 80.0 nm, 82.5 nm, 85.0 nm, 87.5 nm, 90.0 nm, 92.5 nm, 95.0 nm, 97.5 nm, 100.0 nm, 102.5 nm, 105.0 nm, 107.5 nm, 110.0 nm, 112.5 nm, 115.0 nm, 117.5 nm, 120.0 nm, 122.5 nm, 125.0 nm, 127.5 nm, 130.0 nm, 132.5 nm, 135.0 nm, 137.5 nm, 140.0 nm, 142.5 nm, 145.0 nm, 147.5 nm, 150.0 nm, 152.5 nm, 155.0 nm, 157.5 nm, 160.0 nm, 162.5 nm, 165.0 nm, 167.5 nm, 170 nm, 172.5 nm, 175.0 nm, 177.5 nm, 180.0 nm, 182.5 nm, 185.0 nm, 187.5 nm, 190.0 nm, 192.5 nm, 195.0 nm, 197.5 nm, 200.0 nm, 202.5 nm, 205.0 nm, 207.5 nm, 210.0 nm, 212.5 nm, 215.0 nm, 217.5 nm, 220.0 nm, 222.5 nm, 225.0 nm, 227.5 nm, 230.0 nm, 232.5 nm, 235.0 nm, 237.5 nm, 240 nm, 242.5 nm, 245.0 nm, 247.5 nm, 250.0 nm, 252.5 nm, 255.0 nm, 257.5 nm, 260.0 nm, 262.5 nm, 265.0 nm, 267.5 nm, 270 nm, 272.5 nm, 275.0 nm, 277.5 nm, 280.0 nm, 282.5 nm, 285.0 nm, 287.5 nm, 290.0 nm, 292.5 nm, 295.0 nm, 297.5 nm, 300.0 nm, 302.5 ppm, 305.0 ppm, 307.5 ppm, 310.0 ppm, 312.5 ppm, 315.0 ppm, 317.5 ppm, 320.0 ppm, 322.5 ppm or 325.0 ppm in the composition.
In an embodiment disclosed herein, the composition comprises nano or micronized silver or nano or micronized colloidal silver Diferuloylmethane combination 0.1 mcg to 50 mcg. The nano or micronized silver or nano or micronized colloidal silver Diferuloylmethane combination may be 0.1 mcg, 0.5 mcg, 1.0 mcg, 1.5 mcg, 2.0 mcg, 2.5 mcg, 3.0 mcg, 3.5 mcg, 4.0 mcg, 4.5 mcg, 5.0 mcg, 5.5 mcg, 6.0 mcg, 6.5 mcg, 7.0 mcg, 7.5 mcg, 8.0 mcg, 8.5 mcg, 9.0 mcg, 9.5 mcg, 10.0 mcg, 10.5 mcg, 11.0 mcg, 11.5 mcg, 12.0 mcg, 12.5 mcg, 13.0 mcg, 13.5 mcg, 14.0 mcg, about 14.5 mcg, about 15.0 mcg, 15.5 mcg, 16.0 mcg, 16.5 mcg, 17.0 mcg, 17.5 mcg, 18.0 mcg, 18.5 mcg, 19.0 mcg, 19.5 mcg, 20.0 mcg, 20.5 mcg, 22.0 mcg, 22.5 mcg, 23.0 mcg, 23.5 mcg, 24.0 mcg, 24.5 mcg, 25.0 mcg, 27.5 mcg, 30.0 mcg, 32.5 mcg, 35.0 mcg, 37.5 mcg, 40.0 mcg, 42.5 mcg, 45.0 mcg, 47.5 mcg, or 50.0 in the composition.
In an embodiment disclosed herein, the composition comprises nano or micronized silver or nano or micronized colloidal silver Diferuloylmethane combination 0.5 ppm to 400 ppm. The nano or micronized silver or nano or micronized colloidal silver Diferuloylmethane combination may be 0.5ppm, 1ppm, 2.5ppm 5.0 ppm, 7.5 ppm, 10.0 ppm, 12.5 ppm, 15.0 ppm, 17.5 ppm, 20.0 ppm, 22.5 ppm, about 25.0 ppm, 27.5 ppm, 30 ppm, 32.5 ppm, 35.0 ppm, 37.5 ppm, 40.0 ppm, 42.5 ppm, 45.0 ppm, 47.5 ppm, 50 ppm, 52.5 ppm, 55 ppm, 57.5 ppm, 60 ppm, about 62.5 ppm, 65 ppm, 67.5 ppm, 70 ppm, 72.5 ppm, 75 ppm, 77.5 ppm, about 80 ppm, about 82.5 ppm, 85 ppm, 87.5 ppm, 90 ppm, 92.5 ppm, 95 ppm, 97.5 ppm, 100.0 ppm, 102.5 ppm, 105.0 ppm, 107.5 ppm, 110.0 ppm, 112.5 ppm, 115.0 ppm, 117.5 ppm, 120.0 ppm, 122.5 ppm, 125.0 ppm, 127.5 ppm, 130.0 ppm, 132.5 ppm, 135.0 ppm, 137.5 ppm, 140.0 ppm, 142.5 ppm, 145.0 ppm, 147.5 ppm, 150.0 ppm, 152.5 ppm, 155.0 ppm, 157.5 ppm, 160.0 ppm, 162.5 ppm, 165.0 ppm, 167.5 ppm, 170.0 ppm, 172.5 ppm, 175.0 ppm, 172.5 ppm, 175.0 ppm, 177.5 ppm, 180.0 ppm, 182.5 ppm, 185.0 ppm, 187.5 ppm, 190.0 ppm, 192.5 ppm, 195.5 ppm, 197.5 ppm, 200.0 ppm, 202.5 ppm, 205.0 ppm, 207.5 ppm, 210.0 ppm, 212.5 ppm, 215.0 ppm, 217.5 ppm, 220.0 ppm, 222.5 ppm, 225.0 ppm, 227.5 ppm, 230.0 ppm, 232.5 ppm, 235.0 ppm, 237.5 ppm, 240.0 ppm, 242.5 ppm, 245.0 ppm, 247.5 ppm, 250.0 ppm, 252.5 ppm, 255.0 ppm, 257.5 ppm, 260.0 ppm, 262.5 ppm, 265.0 ppm, 267.5 ppm, 270.0 ppm, 272.5 ppm, 275.0 ppm, 272.5 ppm, 275.0 ppm, 277.5 ppm, 280.0 ppm, 282.5 ppm, 285.0 ppm, 287.5 ppm, 290.0 ppm, 292.5 ppm, 295.5 ppm, 297.5 ppm, 300.0 ppm, 302.5 ppm, 305.0 ppm, 307.5 ppm, 310.0 ppm, 312.5 ppm, 315.0 ppm, 317.5 ppm, 320.0 ppm, 322.5 ppm, 325.0 ppm, 327.5 ppm, 330.0 ppm, 332.5 ppm, about 335.0 ppm, 337.5 ppm, 340.0 ppm, 342.5 ppm, 345.0 ppm, 347.5 ppm, 350.0 ppm, 352.5 ppm, 355.0 ppm, 357.5 ppm, 360.0 ppm, 362.5 ppm, 365.0 ppm, 367.5 ppm, 370.0 ppm, 372.5 ppm, 375.0 ppm, 372.5 ppm, 375.0 ppm, 377.5 ppm, 380.0 ppm, 382.5 ppm, 385.0 ppm, 387.5 ppm, 390.0 ppm, 392.5 ppm, 395.0 ppm, 397.5 ppm or 400.0 ppm in the composition.
In an embodiment disclosed herein, the composition comprises nano or micronized silver or nano or micronized colloidal silver or Diferuloylmethane combination having a zeta potential charge ranging from -0.5mV to -50mV. Zeta potential is the potential difference between the dispersion medium and the stationary layer of fluid attached to the particle. The zeta potential charge of nano or micronized gold or nano or micronized colloidal gold may be -0.5mV, -1.0mV, -1.5mV, -2.0mV, -2.5mV, -3.0mV, -3.5mV, -4.0mV, -4.5mV, -5.0mV, -5.5mV, -6.0mV, -6.5mV, -7.0mV, -7.5mV, -8.0mV, -8.5mV, -9.0mV, -9.5mV, -10.0mV, -10.5mV, -11.0mV, -11.5mV, -12.0mV, -12.5mV, -13.0mV, -13.5mV, -14.0mV, -14.5mV, -15.0mV, -15.5mV, -16.0mV, -16.5mV, -17.0mV, -17.5mV, -18.0mV, -18.5mV, -19.0mV, -19.5mV, -20.0mV, -20.5mV, -21.0mV, -21.5mV, -22.0mV, -22.5mV, -23.0mV, -23.5mV, -24.0mV, -24.5mV, -25.0mV, -25.5mV, -26.0mV, -26.5mV, -27.0mV, -27.5mV, -28.0mV, -28.5mV, -29.0mV, -29.5mV, -30.0mV, -30.5mV, -31.0mV, -31.5mV, -32.0mV, -32.5mV, -33.0mV, -33.5mV, -34.0mV, -34.5mV, -35.0mV, -35.5mV, -36.0mV, -36.5mV, -37.0mV, -37.5mV, -38.0mV, -38.5mV, -39.0mV, -39.5mV, -40.0mV, -40.5mV, -41.0mV, -41.5mV, -42.0mV, -42.5mV, -43.0mV, -43.5mV, -44.0mV, -44.5mV, -45.0mV, -45.5mV, -46.0mV, -46.5mV, -47.0mV, -47.5mV, -48.0mV, -48.5mV, -49.0mV, -49.5mV or -50.0mV in the composition.
In an embodiment disclosed herein, the composition comprises nano or micronized silver or nano or micronized colloidal silver with and without Diferuloylmethane with a particle size ranging from about 1 nm to about 300 nm. The Diferuloylmethane or micronized silver or nano or micronized colloidal silver with and without difluoromethane may be of 1 nm, 2 nm, 3 nm, 4 nm, 5 nm, 6 nm, 7 nm, 8 nm, 9 nm, 10, nm, 12.5 nm, 15.0 nm, 17.5 nm, 20.0 nm, 22.5 nm, 25.0 nm, 27.5 nm, 30 nm, 32.5 nm, 35 nm, 37.5 nm, 40.0 nm, 42.5 nm, 45.0 nm, 47.5 nm, 50.0 nm, 52.5 nm, 55.0 nm, 57.5 nm, 60.0 nm, 62.5 nm, 65.0 nm, 67.5 nm, 70.0 nm, 72.5 nm, 75.0 nm, 77.5 nm, 80.0 nm, 82.5 nm, 85.0 nm, 87.5 nm, 90.0 nm, 92.5 nm, 95.0 nm, 97.5 nm, 100.0 nm, 102.5 nm, 105.0 nm, 107.5 nm, 110.0 nm, 112.5 nm, 115.0 nm, 117.5 nm, 120.0 nm, 122.5 nm, 125.0 nm, 127.5 nm, 130.0 nm, 132.5 nm, 135.0 nm, 137.5 nm, 140.0 nm, 142.5 nm, 145.0 nm, 147.5 nm, 150.0 nm, 152.5 nm, 155.0 nm, 157.5 nm, 160.0 nm, 162.5 nm, 165.0 nm, 167.5 nm, 170 nm, 172.5 nm, 175.0 nm, 177.5 nm, 180.0 nm, 182.5 nm, 185.0 nm, 187.5 nm, 190.0 nm, 192.5 nm, 195.0 nm, 197.5 nm, 200.0 nm, 202.5 nm, 205.0 nm, 207.5 nm, 210.0 nm, 212.5 nm, 215.0 nm, 217.5 nm, 220.0 nm, 222.5 nm, 225.0 nm, 227.5 nm, 230.0 nm, 232.5 nm, 235.0 nm, 237.5 nm, 240 nm, 242.5 nm, 245.0 nm, 247.5 nm, 250.0 nm, 252.5 nm, about 255.0 nm, about 257.5 nm, 260.0 nm, 262.5 nm, 265.0 nm, 267.5 nm, 270 nm, 272.5 nm, 275.0 nm, 277.5 nm, 280.0 nm, 282.5 nm, 285.0 nm, 287.5 nm, 290.0 nm, 292.5 nm, 295.0 nm, 297.5 nm or 300.0 nm in the composition.
In an embodiment disclosed herein, the composition comprises nano or micronized silver in solution and is present in an amount ranging from 5 ppm to 200 ppm. The amount of nano or micronized silver may be 5.0 ppm, 7.5 ppm, 10.0 ppm, 12.5 ppm, 15.0 ppm, 17.5 ppm, 20.0 ppm, 22.5 ppm, 25.0 ppm, 27.5 ppm, 30 ppm, 32.5 ppm, 35.0 ppm, 37.5 ppm, 40.0 ppm, 42.5 ppm, 45.0 ppm, 47.5 ppm, 50 ppm, 52.5 ppm, 55 ppm, 57.5 ppm, 60 ppm, 62.5 ppm, 65 ppm, 67.5 ppm, 70 ppm, 72.5 ppm, 75 ppm, 77.5 ppm, 80 ppm, 82.5 ppm, 85 ppm, 87.5 ppm, 90 ppm, 92.5 ppm, 95 ppm, 97.5 ppm, 100.0 ppm, 102.5 ppm, 105.0 ppm, 107.5 ppm, 110.0 ppm, 112.5 ppm, 115.0 ppm, 117.5 ppm, 120.0 ppm, 122.5 ppm, 125.0 ppm, 127.5 ppm, 130.0 ppm, 132.5 ppm, 135.0 ppm, 137.5 ppm, 140.0 ppm, 142.5 ppm, 145.0 ppm, 147.5 ppm, 150.0 ppm, 152.5 ppm, 155.0 ppm, 157.5 ppm, 160.0 ppm, 162.5 ppm, 165.0 ppm, 167.5 ppm, 170.0 ppm, 172.5 ppm, 175.0 ppm, 172.5 ppm, 175.0 ppm, 177.5 ppm, 180.0 ppm, 182.5 ppm, 185.0 ppm, 187.5 ppm, 190.0 ppm, 192.5 ppm, 195.5 ppm, 197.5 ppm or 200.0 ppm in the composition.
In an embodiment disclosed herein, the composition comprises nano or micronized colloidal silver in solution is present in an amount ranging from 20 ppm to 400 ppm. The amount of nano or micronized colloidal silver may be 20.0 ppm, 22.5 ppm, 25.0 ppm, 27.5 ppm, 30 ppm, 32.5 ppm, 35.0 ppm, 37.5 ppm, 40.0 ppm, 42.5 ppm, 45.0 ppm, 47.5 ppm, 50 ppm, 52.5 ppm, 55 ppm, 57.5 ppm, 60 ppm, 62.5 ppm, 65 ppm, 67.5 ppm, 70 ppm, 72.5 ppm, 75 ppm, 77.5 ppm, 80 ppm, 82.5 ppm, 85 ppm, 87.5 ppm, 90 ppm, 92.5 ppm, 95 ppm, 97.5 ppm, 100.0 ppm, 102.5 ppm, 105.0 ppm, 107.5 ppm, 110.0 ppm, 112.5 ppm, 115.0 ppm, 117.5 ppm, 120.0 ppm, 122.5 ppm, 125.0 ppm, 127.5 ppm, 130.0 ppm, 132.5 ppm, 135.0 ppm, 137.5 ppm, 140.0 ppm, 142.5 ppm, 145.0 ppm, 147.5 ppm, 150.0 ppm, 152.5 ppm, 155.0 ppm, 157.5 ppm, 160.0 ppm, 162.5 ppm, 165.0 ppm, 167.5 ppm, 170.0 ppm, 172.5 ppm, 175.0 ppm, 172.5 ppm, 175.0 ppm, 177.5 ppm, 180.0 ppm, 182.5 ppm, 185.0 ppm, 187.5 ppm, 190.0 ppm, 192.5 ppm, 195.5 ppm, 197.5 ppm, 200.0 ppm, 202.5 ppm, 205.0 ppm, 207.5 ppm, 210.0 ppm, 212.5 ppm, 215.0 ppm, 217.5 ppm, 220.0 ppm, 222.5 ppm, 225.0 ppm, 227.5 ppm, 230.0 ppm, 232.5 ppm, 235.0 ppm, 237.5 ppm, 240.0 ppm, 242.5 ppm, 245.0 ppm, 247.5 ppm, 250.0 ppm, 252.5 ppm, 255.0 ppm, 257.5 ppm, 260.0 ppm, 262.5 ppm, 265.0 ppm, 267.5 ppm, 270.0 ppm, 272.5 ppm, 275.0 ppm, 272.5 ppm, 275.0 ppm, 277.5 ppm, 280.0 ppm, 282.5 ppm, 285.0 ppm, 287.5 ppm, 290.0 ppm, 292.5 ppm, 295.5 ppm, 297.5 ppm, 300.0 ppm, 302.5 ppm, 305.0 ppm, 307.5 ppm, 310.0 ppm, 312.5 ppm, 315.0 ppm, 317.5 ppm, 320.0 ppm, 322.5 ppm, 325.0 ppm, 327.5 ppm, 330.0 ppm, 332.5 ppm, 335.0 ppm, 337.5 ppm, 340.0 ppm, 342.5 ppm, 345.0 ppm, 347.5 ppm, 350.0 ppm, 352.5 ppm, 355.0 ppm, 357.5 ppm, 360.0 ppm, 362.5 ppm, 365.0 ppm, 367.5 ppm, 370.0 ppm, 372.5 ppm, 375.0 ppm, 372.5 ppm, 375.0 ppm, 377.5 ppm, 380.0 ppm, 382.5 ppm, 385.0 ppm, 387.5 ppm, 390.0 ppm, 392.5 ppm, 395.0 ppm, 397.5 ppm, or 400.0 ppm in the composition.
In an embodiment disclosed herein, the composition comprises nano or micronized silver or nano or micronized colloidal silver with a particle size ranging from 1 nm to 300 nm. The particle size of nano or micronized gold or nano or micronized colloidal gold may be 1 nm, 2 nm, 3 nm, 4 nm, 5 nm, 6 nm, 7 nm, 8 nm, 9 nm, 10, nm, 12.5 nm, 15.0 nm, 17.5 nm, 20.0 nm, 22.5 nm, 25.0 nm, 27.5 nm, 30 nm, 32.5 nm, 35 nm, 37.5 nm, 40.0 nm, 42.5 nm, 45.0 nm, 47.5 nm, 50.0 nm, 52.5 nm, 55.0 nm, 57.5 nm, 60.0 nm, 62.5 nm, 65.0 nm, 67.5 nm, 70.0 nm, 72.5 nm, 75.0 nm, 77.5 nm, 80.0 nm, 82.5 nm, 85.0 nm, 87.5 nm, 90.0 nm, 92.5 nm, 95.0 nm, 97.5 nm, 100.0 nm, 102.5 nm, 105.0 nm, 107.5 nm, 110.0 nm, 112.5 nm, 115.0 nm, 117.5 nm, 120.0 nm, 122.5 nm, 125.0 nm, 127.5 nm, 130.0 nm, 132.5 nm, 135.0 nm, 137.5 nm, 140.0 nm, 142.5 nm, 145.0 nm, 147.5 nm, 150.0 nm, 152.5 nm, 155.0 nm, 157.5 nm, 160.0 nm, 162.5 nm, 165.0 nm, 167.5 nm, 170 nm, 172.5 nm, 175.0 nm, 177.5 nm, 180.0 nm, 182.5 nm, 185.0 nm, 187.5 nm, 190.0 nm, 192.5 nm, 195.0 nm, 197.5 nm, 200.0 nm, 202.5 nm, 205.0 nm, 207.5 nm, 210.0 nm, 212.5 nm, 215.0 nm, 217.5 nm, 220.0 nm, 222.5 nm, 225.0 nm, 227.5 nm, 230.0 nm, 232.5 nm, 235.0 nm, 237.5 nm, 240 nm, 242.5 nm, 245.0 nm, 247.5 nm, 250.0 nm, 252.5 nm, about 255.0 nm, about 257.5 nm, 260.0 nm, 262.5 nm, 265.0 nm, 267.5 nm, 270 nm, 272.5 nm, 275.0 nm, 277.5 nm, 280.0 nm, 282.5 nm, 285.0 nm, 287.5 nm, 290.0 nm, 292.5 nm, 295.0 nm, 297.5 nm or 300.0 nm in the composition.
In an embodiment disclosed herein, the composition comprises nano or micronized gold solution or nano or micronized colloidal gold having a zeta potential charge ranging from -1mV to -40mV. Zeta potential is the potential difference between the dispersion medium and the stationary layer of fluid attached to the particle. The zeta potential charge of nano or micronized gold or nano or micronized colloidal gold may be -1.0mV, -1.5mV, -2.0mV, -2.5mV, -3.0mV, -3.5mV, -4.0mV, -4.5mV, -5.0mV, -5.5mV, -6.0mV, -6.5mV, -7.0mV, -7.5mV, -8.0mV, -8.5mV, -9.0mV, -9.5mV, -10.0mV, -10.5mV, -11.0mV, -11.5mV, -12.0mV, -12.5mV, -13.0mV, -13.5mV, -14.0mV, -14.5mV, -15.0mV, -15.5mV, -16.0mV, -16.5mV, -17.0mV, -17.5mV, -18.0mV, -18.5mV, -19.0mV, -19.5mV, -20.0mV, -20.5mV, -21.0mV, -21.5mV, -22.0mV, -22.5mV, -23.0mV, -23.5mV, -24.0mV, -24.5mV, -25.0mV, -25.5mV, -26.0mV, -26.5mV, -27.0mV, -27.5mV, -28.0mV, -28.5mV, -29.0mV, -29.5mV, -30.0mV, -30.5mV, -31.0mV, -31.5mV, -32.0mV, -32.5mV, -33.0mV, -33.5mV, -34.0mV, -34.5mV, -35.0mV, -35.5mV, -36.0mV, -36.5mV, -37.0mV, -37.5mV, -38.0mV, -38.5mV, -39.0mV, -39.5mV or -40.0mV in the composition.
The metal nanoparticles, according to embodiments herein, are such that it is capable of being activated when illuminated with light of suitable wavelength, preferably ranging from about 600 nm to about 750 nm.
The composition may further include other generally known additive such as antiallergens, antihistamines, for e.g.: diphenhydramine hydrochloride.
Excipients
The disclosed composition, in the various embodiments herein, may further include one or more pharmaceutical acceptable excipients. The pharmaceutical acceptable excipients include, but is not limited to, solvents, binders, emulsifiers, lubricants, carriers, oils, etc. In an embodiment, the excipient is present in an amount in the range of 0.2 wt% to 70 wt% of the total composition.
Carriers, according to embodiments herein, include hydrophilic and/or hydrophobic solvents, compounds, etc. In an embodiment, the solvent is aqueous solvent, preferably water. In an embodiment, the carriers are selected from water-soluble polymers, water oil -soluble polymer and lipophilic aqueous system. The water soluble polymers, in embodiments herein, may be at least one selected from a group consisting of polyglutamic acid, polyethylene glycol, propylene glycol, glycerol, propylene glycol esters, polyglycerol oleate polyvinyl alcohol, non-ethoxylated polymers like glyceryl stearate (and) Polyglyceryl-6 Palmitate/Succinate (and) Cetearyl Alcohol (NatraGem™ EW) and N-(2-Hydroxypropyl) methacrylamide (PHPMA). Alternatively, other generally known water-soluble polymers may be also used in other embodiments. In another embodiment disclosed herein, the composition comprises of lipophilic aqueous system. Lipophilic aqueous system, in various embodiments herein, includes at least one lipophilic solvent selected from a group consisting of a triglyceride such as fractionated oil, a caprylic triglyceride, an oil containing chain fatty acid triglyceride, isopropyl myristate, isopropyl palmitate, ethyl linoleate, an ethyl oleate ester of fatty acid, propylene glycol dicaprylate, propylene glycol dilaurate and an oil containing propylene glycol fatty acid ester.
The composition, in an embodiment, includes water oil-soluble polymers. The water oil-soluble polymer, in embodiments herein, may be at least one selected from a group of polymers consisting of a polyglutamic acid, a polyethylene glycol, a propylene glycol, glycerol, a propylene glycol ester, a polyglycerol oleate polyvinyl alcohol, and a non-ethoxylated polymer.
The disclosed composition may include the carrier in a suitable amount. In an embodiment, the amount of carriers ranges from 5 wt% to 70 wt% of the composition. In an embodiment, the lipophilic solvent in the composition is present in an amount in the range of about 50 to 200 weight % of the curcuminoid. In an embodiment, the composition includes lipophilic solvent comprising a triglyceride.
Further, the composition, according to embodiments herein, may include one or more emulsifiers, preferably non-ionic oil-in-water emulsifier. In an embodiment, the composition includes at least one non-ionic oil-in-water emulsifier selected from a group consisting of a polyoxyethylene product of a hydrogenated vegetable oil, a polyethoxylated source oil, a polyethoxylated hydrogenated plant source oil, a polyoxyethylene-sorbitan-fatty acid ester and a polyoxyethylene castor oil derivative.
The composition may comprise about 30 wt % to 45 wt % of the non-ionic oil-in-water emulsifier. In an embodiment, the composition comprises emulsifier in the range of about 30%, 35%, 40% or 45% of the total composition.
The composition, according to embodiments herein, may further include a solvent. In an embodiment, the composition includes at least one solvent selected from a group consisting of aqueous water, a polyethylene glycol, glycerol, a polypropylene glycol, and a propylene glycol.
The composition, according to embodiments herein, may further include one or more adsorbents. Further in an embodiment disclosed herein, the adsorbent is selected from a group consisting of a polyethylene glycol, a maltodextrin, a soluble starch, a hydrolysed starch, a fiber, a water soluble oligo saccharide, a chicory, a dextran, a cellulose, a copolymer of polyvinylpyrrolidone, a sugar alcohol, a sorbitol, a xylitol, a mannitol and a cellulose derivative. Further, the composition in some embodiments may include cellulose derivative such as hydroxypropylmethyl cellulose, a hydroxypropyl cellulose, a cyclodextrine or combinations thereof.
The composition, according to embodiments herein may further include one or more diluents, fillers and/or binders. In an embodiment, the composition includes at least one sugar, preferably polyols. Examples of sugars include, but is not limited to, mannitol, a sorbitol; sugars such as lactose, sodium saccharine, Acesulfame K, Alitame, Aspartame, Dextrose, Fructose, Galactose, Inulin, Isomalt, Lactitol, Maltitol, Maltose, Mannitol, Neohesperidin dihydrochalcone, Saccharin, Sodium cyclamate, Sorbitol, Sucralose, Sucrose, Tagatose, Thaumatin, Trehalose and Xylitol, or combinations thereof.
The composition in other embodiments may further include other suitable and pharmaceutically acceptable excipients such as stabilizer, a surfactant, a plasticizer, a lubricant, a reducing agent, a buffering agent, a sweetening agent, a base, a corrigent, a suspending agent, an antioxidant, a polish, a coating, a wetting agent, a gelling agent, a wet modifier, an antifoaming agent, a refrigerative agent, a coloring matter, a flavoring agent, a perfume, a sugar coating agent, an isotonizing agent, a softener, a foaming agent, a pH modifier, an anti-frothing agent, a flavouring agent, a preservatives, a dispersing agent, a disintegrator, a fragrance, a desiccant, an antiseptics, an preservative, a solubilizing agent, a solubilizer, a superplasticizer, an antistatic agent, an extender, a moisturizing agent, or combinations thereof. Those in the art will understand that a number of variations may be made in the disclosed embodiments, all without departing from the scope of the invention. Such variations are understood to fall within the scope of the appended claims.
In an embodiment disclosed herein, the composition further comprises glycerin in an amount ranging from about 0.5% to 30% of the total weight of the composition. The amount of glycine in the composition may be 0.5% 1.0%, 1.5%, 2.0%, 2.5%, 3.0%, 3.5%, 4.0%, 4.5%, 5.0%, 6.0%, 7.0%, 8.0%, 9.0%, 10.0%, 12.5%, 15.0%, 17.5%, 20.0%, 22.5%, 25.0%, 27.5% or 30.0% of the total weight of the composition.
In an embodiment disclosed herein, the composition further comprises polyethylene glycol (PEG) or similar polymer structure with native as well conjugated form in an amount ranging from 0.5% to 25% of the total weight of the composition. The amount of PEG in the composition may be 0.5% 1.0%, 1.5%, 2.0%, 2.5%, 3.0%, 3.5%, 4.0%, 4.5%, 5.0%, 6.0%, 7.0%, 8.0%, 9.0%, 10.0%, 12.5%, 15.0%, 17.5%, 20.0%, 22.5% or 25.0% of the total weight of the composition. Further in an embodiment disclosed herein, the PEG can include, without limitation PEG 100, PEG 200, PEG 300, PEG 400, PEG 500, PEG 600, PEG 700, PEG 800, PEG 900, PEG 1000, PEG 1100, PEG 1200, PEG 1300, PEG 1400, PEG 1500, PEG 1600, PEG 1700, PEG 1800, PEG 1900, PEG 2000, PEG 2100, PEG 2200, PEG 2300, PEG 2400, PEG 2500, PEG 2600, PEG 2700, PEG 2800, PEG 2900, PEG 3000, PEG 3250, PEG 3350, PEG 3500, PEG 3750, PEG 4000, PEG 4250, PEG 4500, PEG 4750, PEG 5000, PEG 5500, PEG 6000, PEG 6500, PEG 7000, PEG 7500, PEG 8000, PEG 8500, PEG 9000, PEG 9500, PEG 10,000, PEG 11,000, PEG 12,000, PEG 13,000, PEG 14,000, PEG 15,000, PEG 16,000, PEG 17,000, PEG 18,000, PEG 19,000, or PEG 20,000. In a preferred embodiment, the PEG is PEG 200. In a more preferred embodiment, the PEG is PEG 400.
In an embodiment disclosed herein, the composition further comprises mannitol in an amount ranging from 10% to 60% of the total weight of the composition. The amount of mannitol in the composition may be 10%, 12.5%, 15%, 17.5%, 20%, 22.5%, 25%, 27.5%, 30%, 32.5%, 35%, 37.5%, 40%, 42.5%, 45%, 47.5%, 50%, 52.5%, 57.5% or 60% of the total weight of the composition.
In an embodiment disclosed herein, the composition further comprises corn starch in an amount ranging from 20% to 50% of the total weight of the composition. The amount of corn starch in the composition may be 20%, 22.5%, 25%, 27.5%, 30%, 32.5%, 35%, 37.5%, 40%, 42.5%, 45%, 47.5% or 50% of the total weight of the composition.
The composition may further comprises one or more pharmaceutically acceptable gelling agents, preferably suitable for achieve semi solid dosage forms such as tragacanth; pectin; starch; carbomer; sodium alginate; cellulose derivatives; gums such as guar gum, xanthan gum, acacia gum, etc; olyvinyl alcohol clays; and gelatin, such as fish gelatin, porcine gelatin, bovine gelatin, etc. In an embodiment, the composition comprises fish gelatin. In another embodiment, the composition comprises bovine gelatin.
Gelatin may be included in the composition in a suitable amount, preferably ranging from 2% to 40% of the total weight of the composition. In an embodiment, the amount of gelatin is about 2.0%, 2.5%, 3.0%, 3.5%, 4.0%, 4.5%, 5.0%, 6.0%, 7.0%, 8.0%, 9.0%, 10.0%, 12.5%, 15.0%, 17.5%, 20.0%, 22.5%, 25.0%, 27.5%, 30.0%, 32.5%, 35%, 37.5% or 40% of the total weight of the composition.
In an embodiment disclosed herein, the composition further comprises sucralose in an amount ranging from 0.1 mg to 5.0 mg. The amount of sucralose in the composition may be 0.1 mg, 0.15 mg, 0.2 mg, 0.25 mg, 0.5 mg, 1.0 mg, 1.5 mg, 2.0 mg equivalent, 2.5 mg, 3 mg, 3.5 mg, 4.0 mg, 4.5 mg, or 5.0 mg.
In an embodiment disclosed herein, the composition further comprises glycine in an amount ranging from 0.5% to 10% of the total weight of the composition. The amount of glycine in the composition may be 0.5%, 1.0%, 1.5%, 2.0%, 2.5%, 3.0%, 3.5%, 4.0%, 4.5%, 5.0%, 5.5%, 6.0%, 6.5%, 7.0%, 7.5%, 8.0%, 8.5%, 9.0%, 9.5% or 10.0%, of the total weight of the composition.
In an embodiment disclosed herein, the composition further comprises mint flavor present in an amount ranging from 0.025% to 1.0% of the total weight of the composition. The amount of mint flavor in the composition may be 0.025%, 0.05%, 0.1%, 0.5%, 0.75% or 1.0% of the total weight of the composition.
In an embodiment disclosed herein, the composition further comprises xanthan gum in an amount ranging from 1% to 60% of the total weight of the composition. The amount of xanthan gum in the composition bypassing first phase metabolism may be 1%, 2.5%, 5.0%, 7.5%, 10%, 12.5%, 15.0%, 17.5%, 20.0%, 22.5%, 25.0%, 27.5%, 30.0%, 32.5%, 35%, 37.5%, 40%, 42.5%, 45%, 47.5%, 50%, 52.5%, 57.5% or 60% of the total weight of the composition.
In an embodiment disclosed herein, the composition further comprises Carbopol 934 in an amount ranging from 1% to 50% of the total weight of the composition. The amount of Carbopol 934 in the composition may be 1%, 2.5%, 5.0%, 7.5%, 10%, 12.5%, 15.0%, 17.5%, 20.0%, 22.5%, 25.0%, 27.5%, 30.0%, 32.5%, 35%, 37.5%, 40%, 42.5%, 45%, 47.5% or 50% of the total weight of the composition.
In an embodiment disclosed herein, the composition further comprises guar gum in an amount ranging from 0.1% to 20% of the total weight of the composition. The amount of guar gum in the composition may be 0.1%, 0.25%, 0.5%, 1.0%, 1.5%, 2.0%, 2.5%, 3.0%, 3.5%, 4.0%, 4.5%, 5.0%, 6.0%, 7.0%, 8.0%, 9.0%, 10.0%, 12.5%, 15.0%, 17.5%, 20.0% of the total weight of the composition.
In an embodiment disclosed herein, the composition further comprises Carbopol 934 and guar gum in a ratio of about 5:1. In a preferred embodiment, the ratio of Carbopol 934 to guar gum in a composition described herein is about 4:1. In a more preferred embodiment, the ratio of Carbopol 934 to guar gum in a composition described herein is about 3:1.
In an embodiment disclosed herein, the composition in a liquid or a solution form comprises a total volume ranging from about 0.1 ml to about 25 ml. The total volume of the composition in a liquid or a solution form described herein may be 0.1 ml, 0.2 ml, 0.3 ml, 0.4 ml, 0.5 ml, 0.6 ml, 0.7 ml, 0.8 ml, 0.9 ml, 1.0 ml, 1.25 ml, 1.5 ml, 1.75 ml, 2.0 ml, 2.25 ml, 2.5 ml, 2.75 ml, 3.0, 3.25 ml, 3.5 ml, 3.75 ml, 4.0 ml, 4.25 ml, 4.5 ml, 4.75 ml, 5.0 ml, 5.25 ml, 5.5 ml, 5.75 ml, 6.0 ml, 6.25 ml, 6.5 ml, 6.75 ml, 7.0 ml, 7.25 ml, 7.5 ml, 7.75 ml, 8.0 ml, 8.25 ml, 8.5 ml, 8.75 ml, 9.0 ml, 9.25 ml, 9.5 ml, 9.75 ml, 10.0 ml, 10.25 ml, 10.5 ml, 10.75 ml, 11.0 ml, 11.25 ml, 11.5 ml, 11.75 ml, 12.0 ml, 12.25 ml, 12.5 ml, 12.75 ml, 13.0 ml, 13.25 ml, 13.5 ml, 13.75 ml, 14.0 ml, 14.25 ml, 14.5 ml, 14.75 ml, 15.0 ml, 15.25 ml, 15.5 ml, 15.75 ml, 16.0 ml, 16.25 ml, 16.5 ml, 16.75 ml, 17.0 ml, 17.25 ml, 17.5 ml, 17.75 ml, 18.0 ml, 18.25 ml, 18.5 ml, 18.75 ml, 19.0 ml, 19.25 ml, 19.5 ml, 19.75 ml, 20.0 ml, 20.25 ml, 20.5 ml, 20.75 ml, 21.0 ml, 21.25 ml, 21.5 ml, 21.75 ml, 22.0 ml, 22.25 ml, 22.5 ml, 22.75 ml, 23.0 ml, 23.25 ml, 23.5 ml, 23.75 ml, 24.0 ml, 24.25 ml, 24.5 ml, 24.75 ml or 25.0 ml.
In an embodiment disclosed herein, the composition is in the form of a solid or a gel with a total weight ranging from 25 mg to 150 mg. The total volume of the composition in a solid or a gel form described herein may be 25 mg, 30 mg, 35 mg, 40 mg, 45 mg, 50 mg, 55 mg, 60 mg, 65 mg, 70 mg, 75 mg, 80 mg, 85 mg, 90 mg, 95 mg, 100 mg, 105 mg, 110 mg, 115 mg, 120 mg, 125 mg, 130 mg, 135 mg, 140 mg, 145 mg or 150 mg.
All weight percentages are based on the total weight of the composition. However, it is apparent that slight variations and modifications in the amount of the ingredients may be practiced without otherwise departing from the intended function of the disclosed composition.
In certain embodiment, the disclosure contemplates composition comprising various combination of components such as photosensitizers, metal particles, phospholipids, excipients, carriers etc, are contemplated. In an embodiment, the composition comprises Phenothiazinium, nano or micronized colloidal metal nanoparticles, non-hydrogenated phosphatidylcholine sunflower, glycerin, PEG 400 and purified water. In another embodiment, the composition comprises Phenothiazinium, Diferuloylmethane, nano or micronized silver, non-hydrogenated phosphatidylcholine sunflower, glycerin, PEG 400 and purified water. In yet another embodiment, the composition comprises of Phenothiazinium, non-hydrogenated phosphatidylcholine sunflower, glycerin, PEG 400 and purified water.
In an embodiment, the composition comprises of Phenothiazinium, Diferuloylmethane, non-hydrogenated phosphatidylcholine sunflower, glycerin, PEG 400 and purified water. In another embodiment, the composition comprises of Phenothiazinium, non-hydrogenated phosphatidylcholine sunflower, glycerin, PEG 400 and purified water. In another embodiment, the composition comprises of Phenothiazinium, Diferuloylmethane, nano or micronized silver, non-hydrogenated phosphatidylcholine, glycerin, PEG 400 and purified water. In another embodiment, the composition comprises of Phenothiazinium, nano or micronized colloidal metal nanoparticles, hydrogenated phosphatidylcholine, glycerin, PEG 400 and purified water.
In another embodiment, the composition comprises of Phenothiazinium, nano or micronized silver, hydrogenated phosphatidylcholine, glycerin, PEG 400 and purified water. In another embodiment, the composition comprises of Phenothiazinium, hydrogenated phosphatidylcholine, glycerin, PEG 400 and purified water. In another embodiment, the composition comprises of Phenothiazinium, hydrogenated phosphatidylcholine soybean, glycerin, PEG fatty chain and purified water.
Further, in another embodiment, the composition comprises of Phenothiazinium, nano or micronized metal nanoparticles, hydrogenated phosphatidylcholine soybean, glycerin, PEG 400 and purified water. In another embodiment, the composition comprises of Phenothiazinium, nano or micronized metal nanoparticles, non-hydrogenated phosphatidylcholine soybean, glycerin, PEG 400 and purified water. In another embodiment, the composition comprises of Phenothiazinium, nano or micronized metal nanoparticles, non-hydrogenated phosphatidylcholine soybean, glycerin, PEG 400 and purified water. In yet another embodiment, the composition comprises of Phenothiazinium, nano or micronized metal nanoparticles, non-hydrogenated phosphatidylcholine sunflower, mannitol, corn starch and purified water.
Further, in an embodiment, the composition comprises of Phenothiazinium, Diferuloylmethane, nano or micronized silver, non-hydrogenated phosphatidylcholine sunflower, mannitol, gelatin-fish, corn starch and purified water. In another embodiment, the composition comprises of Phenothiazinium, nano or micronized silver, phosphatidylcholine sunflower, mannitol, gelatin fish, mint flavor, sucralose and purified water. In another embodiment, the composition comprises of Phenothiazinium, nano or micronized silver, non-hydrogenated phosphatidylcholine, mannitol, bovine gelatin, mint flavor and sucralose. In another embodiment, the composition comprises of Phenothiazinium, nano or micronized metal nanoparticles, hydrogenated phosphatidylcholine, glycine, gelatin-fish, mannitol, mint flavor, sucralose and purified water.
In an embodiment, the composition comprises of Phenothiazinium, nano or micronized metal nanoparticles, phosphatidylcholine, xanthan gum and purified water.
In another embodiment, the composition comprises of Phenothiazinium, Diferuloylmethane, nano or micronized metal nanoparticles, phosphatidylcholine, Carbopol-934, guar gum and purified water. Further, in an embodiment, the composition comprises of Phenothiazinium, nano or micronized metal nanoparticles, phosphatidylcholine, Carbopol-934 and purified water.
The composition, according to embodiments herein is preferably a clear solution liquid composition capable of remaining in clear solution form without precipitation or separation of particles for a minimum period of about 24 hours. In an embodiment, the disclosed composition is a homogenous composition. The disclosed composition is capable of bypassing first pass metabolism, preferably as its ability as a homogenous composition to result into a clear and transparent solution, without precipitation or separation of particles for a minimum period of 20 minutes when added to water in ratio of 1: 200 and above. Embodiments herein provide stable compositions. The composition, according to an embodiment herein, is stabilized such that the composition when stored at normal ambient conditions (eg: at temperature 25 ±2 degrees Celsius and Relative Humidity 60% ±5) is stable in aqueous phase, after about 1:200 dilution, for a period of up to 4 months. The composition is suitable for sublingual administration, having no or reduced phase separation.
Dosage Form
The composition, according to embodiments herein, may further be formulated into any suitable dosage form. Various dosage forms of the composition are contemplated in the present disclosure. Generally known dosage forms, including, but not limited to, liquid forms including colloids; injectables, emulsion, suspensions, dispersion, etc; solid forms such as capsules, lozenges, powder, lyophilized cakes, granules; semisolid forms including gel, cream, lotions, etc; gaseous forms including aerosols. In an embodiment, the dosage form is suited for oromucosal route of administration eg: buccal, sublingual, etc. In another embodiment, the composition is administered intraorally and the components be prepared for uptake in a manner that makes the composition available in therapeutically effective amounts. As such, they may also be prepared as water soluble compositions, deliverable in encapsulated, or in a manner suitable for time release, delayed release or any manner typically used for delivery of pharmaceuticals, nutraceuticals or vitamins, etc. In some embodiments, the composition may also be administered intranasally and intravenously
In an embodiment, the disclosed composition is formulated in the form of tablets. Generally known methods of formulating/processing compositions may be used to formulate the desired dosage forms. In an embodiment, the disclosed composition is formulated in the form of tablets, preferably with a total weight ranging from about 40 mg to 100 mg. Further in an embodiment, the composition is in the form of orally soluble tablet, preferably capable of dissolving within 2 to 30 minutes, preferably 5 to 10 minutes, under tongue or in buccal cavity. In an embodiment, orally soluble tablet is a lozenge.
In an embodiment, the composition is an oral liquid dosage form eg: solution, suspension, dispersion, etc. In a preferable embodiment, the oral solution has a total volume ranging from about 0.1 ml to 25 ml.
In other embodiment, the composition is a semisolid dosage form. The semisolid form may be selected from the group consisting of solution, lotion, cream, ointment, gel, paste, aerosol foam or spray. In an embodiment, the semisolid form comprises a total weight ranging from 0.25 mg to 50 mg.
In an embodiment, the composition is an oral solid dosage form eg: tablets, capsule, lozenges, powder, granules, pellets, etc In an embodiment, the composition is an Orally Disintegrating dosage form selected from Tablet (ODT) or capsule or tablet in capsule, or a hard sugar boiled lozenge. In an embodiment, the orally disintegrating dosage form is such that it dissolves in mouth within a period of 1 minute to 30 minutes, preferably from 1 minute to 2 minutes. . It will be apparent to those skilled in the art that many modifications, both to materials and methods, may be practiced without departing from the scope of the claims herein.
The embodiments herein may be packaged into suitable form. Processing techniques and type of packaging would vary depending on dosage forms. For example, tablets are generally compressed by tablet pressers under pressure; capsules involve capsule filling operations; granules generally involve wet granulation techniques, etc. Example of packaging include ampoules, sachet packaging, vials, dosing doppler, containers, strip package, blister packaging, syringe. In an embodiment, blister packaging is used.
Embodiments are further described herein by reference to the following examples by way of illustration only and should not be construed to limit the scope of the claims provided herewith. Various exemplary embodiments of the disclosed composition are described hereunder. Table 1, Table 2, Table 3, Table 4, Table 5, Table 6, Table 7, Table 8, Table 9, Table 10, Table 11, Table 12, Table 13, Table 14, Table 15, Table 16 and Table 17 provide details of exemplary embodiments depicting different liquid compositions comprising Phenothiazinium.
Table 1: Composition - 1
Item No. Ingredient Qty. / 1ml % Percentage
(mg)
1 Phenothiazinium, USP 5.0 mg equivalent 0.5
2 20 ppm nano or micronized colloidal gold 4.5 mcg 0.000045
3 20 ppm nano or micronized colloidal silver 6.5 mcg 0.000065
4 Non-Hydrogenated Phosphatidylcholine Sunflower 30 mg 3
5 Glycerin, USP 25 mg 2.5
6 PEG 400, USP 20 mg 2
7 Purified water, USP q.s.
TOTAL
**Sterile water for Irrigation evaporates during the process and therefore does not appear in the total.

Table 2: Composition - 2
Item No. Ingredient Qty. / 1ml % Percentage
(mg)
1 Phenothiazinium, USP 5.0 mg equivalent 0.5
2 Diferuloylmethane 5.0 mg equivalent 0.5
3 20 ppm nano or micronized silver 6.5 mcg 0.000065
4 Non-Hydrogenated Phosphatidylcholine Sunflower 30 mg 3
5 Glycerin, USP 25 mg 2.5
6 PEG 400, USP 20 mg 2
7 Purified water, USP q.s.
TOTAL
**Sterile water for Irrigation evaporates during the process and therefore does not appear in the total.

 
Table 3: Composition - 3
Item No. Ingredient Qty. / 1ml % Percentage
(mg)
1 Phenothiazinium, USP 5.0 mg equivalent 0.5
2 Non-Hydrogenated Phosphatidylcholine Sunflower 30 mg 3
3 Glycerin, USP 25 mg 2.5
4 PEG 400, USP 20 mg 2
5 Purified water, USP q.s.
TOTAL
**Sterile water for Irrigation evaporates during the process and therefore does not appear in the total.

Table 4: Composition - 4
Item No. Ingredient Qty. / 1ml % Percentage
(mg)
1 Phenothiazinium, USP 1.0 mg equivalent 0.1
2 Diferuloylmethane 1.0 mg equivalent 0.1
3 Non-Hydrogenated Phosphatidylcholine Sunflower 30 mg 3
4 Glycerin, USP 25 mg 2.5
5 PEG 400, USP 20 mg 2
6 Purified water, USP q.s.
TOTAL
**Sterile water for Irrigation evaporates during the process and therefore does not appear in the total.

Table 5: Composition - 5
Item No. Ingredient Qty. / 1ml % Percentage
(mg)
1 Phenothiazinium, USP 1.0 mg equivalent 0.1
2 Non-Hydrogenated Phosphatidylcholine Sunflower 5 mg 0.5
3 Glycerin, USP 50 mg 5
4 PEG 400, USP 30 mg 3
5 Purified water, USP q.s.
TOTAL
**Sterile water for Irrigation evaporates during the process and therefore does not appear in the total.

Table 6: Composition - 6
Item No. Ingredient Qty. / 1ml % Percentage
(mg)
1 Phenothiazinium, USP 10.0 mg equivalent 1
2 20 ppm nano or micronized gold 1.0 mcg 0.000001
3 20 ppm nano or micronized silver 10.0 mcg 1
2 Non-Hydrogenated Phosphatidylcholine Sunflower 20 mg 1
3 Glycerin, USP 15 mg 1.5
4 PEG 400, USP 30 mg 3
5 Purified water, USP q.s.
TOTAL
**Sterile water for Irrigation evaporates during the process and therefore does not appear in the total.

Table 7: Composition - 7
Item No. Ingredient Qty. / 1ml % Percentage
(mg)
1 Phenothiazinium, USP 7.5 mg equivalent 0.75
2 Diferuloylmethane 7.5 mg equivalent 0.25
3 20 ppm nano or micronized silver 1.0 mcg 0.00001
4 Non-Hydrogenated Phosphatidylcholine 40 mg 4
5 Glycerin, USP 30 mg 3
6 PEG 400, USP 10 mg 1
7 Purified water, USP q.s.
TOTAL
**Sterile water for Irrigation evaporates during the process and therefore does not appear in the total.

Table 8: Composition - 8
Item No. Ingredient Qty. / 1ml % Percentage
(mg)
1 Phenothiazinium, USP 5.0 mg equivalent 0.5
2 20 ppm nano or micronized colloidal gold 4.5 mcg 0.000045
3 20 ppm nano or micronized colloidal silver 6.5 mcg 0.000065
4 Hydrogenated Phosphatidylcholine 30 mg 3
5 Glycerin, USP 25 mg 2.5
6 PEG 400, USP 20 mg 2
7 Purified water, USP q.s.
TOTAL
**Sterile water for Irrigation evaporates during the process and therefore does not appear in the total.

Table 9: Composition - 9
Item No. Ingredient Qty. / 1ml % Percentage
(mg)
1 Phenothiazinium, USP 5.0 mg equivalent 0.5
2 20 ppm nano or micronized silver 6.5 mcg 0.000065
3 Hydrogenated Phosphatidylcholine 30 mg 3
4 Glycerin, USP 25 mg 2.5
5 PEG 400, USP 20 mg 2
6 Purified water, USP q.s.
TOTAL
**Sterile water for Irrigation evaporates during the process and therefore does not appear in the total.

Table 10: Composition - 10
Item No. Ingredient Qty. / 1ml % Percentage
(mg)
1 Phenothiazinium, USP 5.0 mg equivalent 0.5
2 Hydrogenated Phosphatidylcholine 30 mg 3
3 Glycerin, USP 50 mg 5
4 PEG 400, USP 40 mg 4
5 Purified water, USP q.s.
TOTAL
**Sterile water for Irrigation evaporates during the process and therefore does not appear in the total.

 
Table 11: Composition - 11
Item No. Ingredient Qty. / 1ml % Percentage
(mg)
1 Phenothiazinium, USP 5.0 mg equivalent 0.5
2 Hydrogenated Phosphatidylcholine Soybean 30 mg 3
3 Glycerin, USP 50 mg 5
4 PEG Fatty chain 40 mg 4
5 Purified water, USP q.s.
TOTAL
**Sterile water for Irrigation evaporates during the process and therefore does not appear in the total.

Table 12: Composition - 12
Item No. Ingredient Qty. / 1ml % Percentage
(mg)
1 Phenothiazinium, USP 5.0 mg equivalent 0.5
2 20 ppm nano or micronized gold 4.5 mcg 0.000045
3 20 ppm nano or micronized silver 6.5 mcg 0.000065
4 Non-Hydrogenated Phosphatidylcholine Soyabean 30 mg 3
5 Glycerin, USP 25 mg 2.5
6 PEG 400, USP 20 mg 2
7 Purified water, USP q.s.
TOTAL
**Sterile water for Irrigation evaporates during the process and therefore does not appear in the total.

Table 13: Composition - 13
Item No. Ingredient Qty. / 1ml % Percentage
(mg)
1 Phenothiazinium, USP 5.0 mg equivalent 0.5
2 20 ppm nano or micronized gold 2.0 mcg 0.000002
3 20 ppm nano or micronized silver 1.5 mcg 0.0000015
4 Non-Hydrogenated Phosphatidylcholine Soyabean 30 mg 3
5 Glycerin, USP 25 mg 2.5
6 PEG 400, USP 20 mg 2
7 Purified water, USP q.s.
TOTAL
**Sterile water for Irrigation evaporates during the process and therefore does not appear in the total.

Table 14: Composition - 14
Item No. Ingredient Qty. / 1ml % Percentage
(mg)
1 Phenothiazinium, USP 5.0 mg equivalent 0.5
2 20 ppm nano or micronized gold 2.0 mcg 0.000002
3 20 ppm nano or micronized silver 1.5 mcg 0.0000015
4 Hydrogenated Phosphatidylcholine Soyabean 30 mg 3
5 Glycerin, USP 25 mg 2.5
6 PEG 400, USP 20 mg 2
7 Purified water, USP q.s.
TOTAL
**Sterile water for Irrigation evaporates during the process and therefore does not appear in the total.

Table 15: Composition - 15
Item No. Ingredient Qty. / 1ml % Percentage
(mg)
1 Phenothiazinium, USP 5.0 mg equivalent 0.5
2 5 ppm nano or micronized gold 4.5 mcg 0.000045
3 40 ppm nano or micronized silver 6.5 mcg 0.000065
4 Non-Hydrogenated Phosphatidylcholine Sunflower 30 mg 3
5 Glycerin, USP 25 mg 2.5
6 PEG 400, USP 20 mg 2
7 Purified water, USP q.s.
TOTAL
**Sterile water for Irrigation evaporates during the process and therefore does not appear in the total.

 
Table 16: Composition - 16
Item No. Ingredient Qty. / 0.5ml % Percentage
(mg)
1 Phenothiazinium, USP 5.0 mg equivalent 1
2 20 ppm nano or micronized gold 4.5 mcg 0.0009
3 20 ppm nano or micronized silver 6.5 mcg 0.00013
4 Non-Hydrogenated Phosphatidylcholine Soybean 30 mg 6
5 Glycerin, USP 25 mg 5
6 PEG 400, USP 20 mg 4
7 Purified water, USP q.s.
TOTAL
**Sterile water for Irrigation evaporates during the process and therefore does not appear in the total.

Table 17: Composition - 17
Item No. Ingredient Qty. / 0.1ml % Percentage
(mg)
1 Phenothiazinium, USP 5.0 mg equivalent 10
2 20 ppm nano or micronized gold 4.5 mcg 0.0045
3 20 ppm nano or micronized silver 6.5 mcg 0.0066
4 Non-Hydrogenated Phosphatidylcholine Soybean 30 mg 30
5 Glycerin, USP 25 mg 25
6 PEG 400, USP 20 mg 20
7 Purified water, USP q.s.
TOTAL

Table 18, Table 19, Table 20, Table 21 and Table 22 are an exemplary embodiment depicting different fast dissolve tablet compositions comprising Phenothiazinium. All fast dissolve tablet composition bypassing first phase metabolism comprise 40-100 mg tablets.
 
Table 18: Composition – 18
Item No. Ingredient Qty. / tab % Percentage
(mg)
1 Phenothiazinium, USP 5.0 mg equivalent 5
2 20 ppm nano or micronized gold 4.5 mcg 0.0045
3 20 ppm nano or micronized silver 6.5 mcg 0.0065
4 Non-Hydrogenated Phosphatidylcholine Sunflower 30 mg 30
5 Mannitol, USP 50 mg 50
6 Corn starch, USP 40 mg 40
7 Purified water, USP q.s.
TOTAL
**Sterile water for Irrigation evaporates during the process and therefore does not appear in the total.

Table 19: Composition– 19
Item No. Ingredient Qty. / tab % Percentage
(mg)
1 Phenothiazinium, USP 1.0 mg equivalent 1
2 Diferuloylmethane 1.0 mg equivalent 1
3 20 ppm nano or micronized silver 10 mcg 0.001
4 Non-Hydrogenated Phosphatidylcholine Sunflower 30 mg 30
5 Mannitol, USP 50 mg 50
6 Gelatin-Fish 5.0 mg 5
7 Corn starch, USP 40 mg 40
8 Purified water, USP q.s.
TOTAL
**Sterile water for Irrigation evaporates during the process and therefore does not appear in the total.

Table 20: Composition – 20
Item No. Ingredient Qty. / tab % Percentage
(mg)
1 Phenothiazinium, USP 1.0 mg equivalent 1
2 20 ppm nano or micronized silver 10 mcg 0.001
3 Phosphatidylcholine Sunflower 40 mg 40
4 Mannitol 20 mg 20
5 Gelatin-Fish 10 mg 10
6 Mint flavor 0.25 mg 0.25
7 Sucralose 0.25 mg 0.25
TOTAL
**Sterile water for Irrigation evaporates during the process and therefore does not appear in the total.

Table 21: Composition – 21
Item No. Ingredient Qty. / tab % Percentage
(mg)
1 Phenothiazinium, USP 5.0 mg equivalent 5
2 20 ppm nano or micronized silver 6.0 mcg 0.006
3 Non-hydrogenated Phosphatidylcholine 40 mg 40
4 Mannitol 20 mg 20
5 Bovine Gelatin 10 mg 10
6 Mint flavor 0.25 mg 0.25
7 Sucralose 0.25 mg 0.25
TOTAL
**Sterile water for Irrigation evaporates during the process and therefore does not appear in the total.

Table 22: Composition – 22
Item No. Ingredient Qty. / tab % Percentage
(mg)
1 Phenothiazinium, USP 5.0 mg equivalent 5
2 20 ppm nano or micronized gold 4.5 mcg 0.0045
3 20 ppm nano or micronized silver 6.5 mcg 0.0065
4 Hydrogenated Phosphatidylcholine 30 mg 3
5 Glycine, USP 5 mg 5
6 Gelatin-Fish (HMW) 20 mg 20
7 Mannitol 25 mg 25
8 Mint flavor 0.2 mg 0.2
9 Sucralose 0.5 mg 0.5
10 Purified water, USP q.s.
TOTAL

Table 23, Table 24 and Table 25 are an exemplary embodiment depicting different gel compositions comprising Phenothiazinium.
Table 23: Composition – 23
Item No. Ingredient Qty. / gel % Percentage
(mg)
1 Phenothiazinium, USP 5.0 mg equivalent 5
2 20 ppm nano or micronized gold 4.5 mcg 0.0045
3 20 ppm nano or micronized silver 6.5 mcg 0.0065
4 Phosphatidylcholine 30 mg 30
5 Xanthan gum USP 60 mg 60
6 Purified water, USP q.s.
TOTAL
**Sterile water for Irrigation evaporates during the process and therefore does not appear in the total.

Table 24: Composition – 24
Item No. Ingredient Qty. / gel % Percentage
(mg)
1 Phenothiazinium, USP 5.0 mg equivalent 5
2 Diferuloylmethane 5.0 mg equivalent 5
3 20 ppm nano or micronized gold 4.5 mcg 0.0045
4 20 ppm nano or micronized silver 6.5 mcg 0.0065
5 Phosphatidylcholine 30 mg 30
6 Carbopol 934 50 mg 50
7 Guar gum
8 Purified water, USP q.s.
TOTAL
**Sterile water for Irrigation evaporates during the process and therefore does not appear in the total.

Table 25: Composition – 25

Item No. Ingredient Qty. / gel % Percentage
(mg)
1 Phenothiazinium, USP 5.0 mg equivalent 5
2 20 ppm nano or micronized gold 4.5 mcg 0.0045
3 20 ppm nano or micronized silver 6.5 mcg 0.0065
4 Phosphatidylcholine 30 mg 30
5 Carbopol 934 60 mg 60
6 Purified water, USP q.s.
TOTAL
In exemplary embodiments, the gelatin, Carbopol 934 and their combinations of Phenothiazinium gels were transparent while Hydroxypropyl methyl cellulose (HPMC) and sodium CMC (carboxymethylcellulose) gels were white viscous and sodium alginate and guar gum gels were brownish gummy with smooth and homogeneous appearance. Viscosity is an important physical property of topical composition, which affects the rate of drug release.

Method
Disclosed herein are embodiments of a method for preparing the disclosed composition. The composition may be formulated by techniques generally known in the art including, but not limited to, nano/micro precipitation, which can be carried out by methods such as sonication, emulsification, solvent titration, milling, spray drying, solid dispersion, hot-melt extrusion, freeze drying methods, or supercritical fluid technology.
In an embodiment, the method comprises mixing phenothiazinium with suitable solvent to obtain diluted phenothiazinium; adding phospholipid, or lysolipid thereof, or derivatives thereof, and liquid mixing to obtain stabilized phenothiazinium mixture; adding metal micronized and/or nanoparticles; adding one or more suitable excipients and solvent; and mixing. Mixing may be done by any suitable method generally known in the field including, but not limited to liquid mixing, blending, sonicating, magnetic stirring, etc, using equipment such as sonicator, magnetic stirrer, blender, mixer, etc. Mixing may be done for a period in the range of about 5 to 30 minutes. In an embodiment, mixing is performed for about 15 to 20 minutes, preferably 15 minutes. In an embodiment, mixing is done to disperse solutes or components of the composition, and preferably achieve homogenous compositions. In an embodiment, the solvent is deionized water. Preferably, mixing is performed after or during the addition of each component. In another embodiment, the solvent comprises deionized water and diluted glycerin solution.
In another embodiment, the method comprises mixing phenothiazinium with suitable solvent to obtain diluted phenothiazinium; mixing phospholipid and the diluted phenothiazinium; adding metal nanoparticles; adding diferuloylmethane and mixing; adding one or more suitable excipients and mixing.
In an embodiment, the method includes, mixing Phenothiazinium with purified water, adding diluted glycerin; adding phospholipid; adding metal nano and/or micro particles and at least one excipient selected from PEG, mannitol, corn starch, fish gelatin, bovine gelatin, mint flavor, sucralose, xanthan gum, Carbopol 934, and gaur gum.
In an embodiment described herein, the method for preparing a composition comprises liquid mixing Phenothiazinium with purified water; mixing phospholipid selected from the group consisting of phosphatidylcholine, lyso-phophatidylcholine, and a combination thereof; nano or micronized gold and/or nano or micronized silver, PEG; and glycerin, Diferuloylmethane powder form.
In an embodiment, the method comprises mixing phenothiazinium with purified water to obtain diluted phenothizinium; mixing phospholipid and the diluted phenothiazinium; adding nano or micronized gold and/or nano or micronized silver; adding PEG and glycerin and finally mixing.
In another embodiment, the method comprises blending Phenothiazinium, phosphatidylcholine, nano or micronized gold and/or nano or micronized silver with purified water; adding at least one excipient such as PEG, cyclodextrin or gum; blending and mixing to achieve semisolid dosage form, particularly gel form.
In an embodiment described herein, the method for preparing a composition comprises a step of hydrate mixing after at least one of the liquid mixing steps or upon completion of two or more components of the composition as described above, to obtain a hydrated mixture. Hydrated mixture may be achieved by liquid mixing for a period in the range of about 5 to 150 minutes, preferably for 45 minutes to 150 minutes, more preferably for about 120 minutes. In an embodiment, mixing is performed for about 15 to 20 minutes, preferably 15 minutes. Further in an embodiment described herein, the process for preparing composition comprises a step of sonicating the hydrated mixture. Sonication is performed for a suitable time so as to achieve even dispersion of solutes or component of the composition, such as nano/micro particles, and is preferably performed upon addition of gold/silver nano/micronized particles. In an embodiment, sonication is performed for a period of about 5 minutes to about 15 minutes at room temperature or in an ice bath at a preferable amplitude of about 20 to about 75 units.
Further in an embodiment described herein, the method for preparing a composition comprises a step of liquid mixing hydrated mixture and PEG to obtain a mixture of hydrated mixture and PEG. Further in an embodiment described herein, the method for preparing a composition comprises a step of sonicating the mixture of hydrated mixture and PEG.
Further in an embodiment described herein, the method for preparing a composition comprises a step of liquid mixing one or more agents selected from the group consisting of mannitol, corn starch, gelatin-fish, bovine-fish, sucralose, flavoring, xanthan gum, Carbopol 934, and guar gum after at least one of the liquid mixing steps described in previous embodiments.
In some embodiments, the method further comprises a step of inducing low level light, preferably to accelerate formulation, in the range of 610 to 670 nm from LED for about 30 to 80 minutes, preferably 50 minutes.
The method may further include additional steps to achieve various suitable dosage form. Examples of such additional steps include tableting, pressing, drying, milling, wet or dry granulating, blending, encapsulation, and packaging. Such steps are generally known and may be suited to achieve various forms of the present composition. In an embodiment, the disclosed composition is subjected
Process for preparing liquid dosage forms
For liquid dosage forms, phenothiazinium is mixed by liquid mixing with purified water to obtain diluted Phenothiazinium. Diluted glycerin is then prepared by mixing glycerin with purified water. Further, diluted phospholipid is prepared by mixing phospholipid with diluted mixture of Phenothiazinium and glycerin. Liquid mixing is performed for 5 minutes to 30 minutes, preferably for 10 minutes to 20 minutes, more preferably for 15 minutes using a magnetic stirrer. Liquid mixing is preferably performed in order obtain a hydrated mixture. Hydrated mixture is achieved by liquid mixing for about 120 minutes. Further, metal nano/micro particles were added, and liquid mixing is continued for about 5 minutes. The mixture is then sonicated for about 15 minutes, at an amplitude of 5 to 70 units, at either room temperature or in a cold condition between 0 to 5 Degrees Celsius.
Further, PEG is added, and liquid mixing performed. The solution was then subjected to homogenization step, wherein entire or partial solution or suspension is homogenized at maximum speeds of about 20% to 75% power using a mesh stator (PAMPA Model) of 10 to 100 mesh at either room temperature or in a cold bath environment.
The solution is optionally filtered through a Amicon Ultra-15 or similar porosity of filter used in a centrifuge, wherein 20% of solution is captured on the filter and 80% pass through by weight, or preferably, wherein 50% of solution is captured on the filter and 50 % pass through by weight, or more preferably, wherein 80% of solution is captured on the filter and 20 % pass through by weight, or even more preferably, wherein 100% of solution is captured on the filter and 0 % pass through by weight of the Phenothiazinium as either a liquid or suspension.
Embodiments of the method of preparation of compositions are further described herein by reference to the following examples by way of illustration only and should not be construed to limit the scope of the claims provided herewith. Various exemplary embodiments of the method are described hereunder.
Example 1: Phenothiazinium, phospholipid, nano or micronized gold and/or nano or micronized silver, nano or micronized colloidal gold and/or nano or micronized colloidal silver, glycerin and purified water were mixed; hydrate mixed for 120 minutes followed by sonication for 15 minutes at room temperature or in an ice bath at an amplitude of 15 to 80 units and PEG 400 was then added and mixed for 15 minutes to obtain the disclosed composition.
Example 2: Phenothiazinium, phospholipid, glycerin and purified water were mixed for 15 minutes; hydrate mixed for 120 minutes followed addition of by nano or micronized gold and/or nano or micronized silver, nano or micronized colloidal gold and/or nano or micronized colloidal silver and mixed for 15 minutes; sonication for 1 minute to 30 minutes at room temperature or in an ice bath at an amplitude of 20 to 75 and PEG 400 was then added and mixed for 15 minutes to obtain the disclosed composition.
Example 3: Phenothiazinium, Diferuloylmethane, phospholipid, glycerin and purified water were mixed for 12 minutes to 20 minutes; hydrate mixed for 120 minutes to 160 minutes followed by addition of nano or micronized gold and/or nano or micronized silver, nano or micronized colloidal gold and/or nano or micronized colloidal silver and mixed for 12 minutes to 20 minutes; sonication for 1 minute to 30 minutes at room temperature or in an ice bath at an amplitude of 15 to 80 and PEG 400 was then added and mixed for 15 minutes to obtain the disclosed composition.
Example 4: Phenothiazinium, glycerin and purified water were mixed for 15 minutes; phospholipid was added and mixed for 15 minutes; hydrate mixed for 120 minutes followed by addition of nano or micronized gold and/or nano or micronized silver, nano or micronized colloidal gold and/or nano or micronized colloidal silver and mixed for 15 minutes; sonication for 1 minute to 30 minutes at room temperature or in an ice bath at an amplitude of 20 to 75 and PEG 400 was then added and mixed for 15 minutes to obtain the disclosed composition.
Example 5: Phenothiazinium and glycerin were mixed with purified water separately for 15 minutes each; both mixtures were added together and mixed further for 15 minutes; hydrate mixed for 120 minutes followed by addition of nano or micronized gold and/or nano or micronized silver, nano or micronized colloidal gold and/or nano or micronized colloidal silver and mixed for 15 minutes; sonication for 1 minute to 30 minutes at room temperature or in an ice bath at an amplitude of 15 to 80 and PEG 400 was then added and mixed for 12 minutes to 20 minutes to obtain the disclosed composition.
Example 6: Phenothiazinium, glycerin and purified water were mixed for 15 minutes; phospholipid was added and mixed for 15 minutes; hydrate mixed for 120 minutes followed by sonication for 1 minute to 30 minutes at room temperature or in an ice bath at an amplitude of 20 to 75 and PEG 400 was then added and mixed for 15 minutes to obtain the disclosed composition. To accelerate the composition, low level light of 610 nm and 670 nm from LED was further used for 50 minutes.
Example 7: Phenothiazinium, glycerin and purified water were mixed for 15 minutes; phospholipid was added and mixed for 15 minutes; hydrate mixed for 120 minutes followed by addition of nano or micronized silver or nano or micronized colloidal silver and mixed for 15 minutes; sonication for 1 minute to 30 minutes at room temperature or in an ice bath at an amplitude of 20 to 75 and PEG 400 was then added and mixed for 15 minutes to obtain the disclosed composition. To accelerate the composition, low level light of 610 nm and 670 nm from LED was further used for 50 minutes.
Example 8: Phenothiazinium, glycerin and purified water were mixed for 15 minutes; phospholipid was added and mixed for 15 minutes; hydrate mixed for 120 minutes followed by addition of nano or micronized gold and/or nano or micronized silver or nano or micronized colloidal gold and/or nano or micronized colloidal silver and mixed for 15 minutes; sonication for 1 minute to 30 minutes at room temperature or in an ice bath at an amplitude of 20 to 75 and PEG 400 was then added and mixed for 15 minutes to obtain the disclosed composition. To accelerate the composition, low level light of 610 nm and 670 nm from LED was further used for 50 minutes.
Example 9: Phenothiazinium, Diferuloylmethane, nano or micronized gold and/or nano or micronized silver or nano or micronized colloidal gold and/or nano or micronized colloidal silver, a non-ionic oil in water emulsifier and a solvent were mixed to form a uniform blend; alternate sonication and resting was carried out for 20 and 25 seconds for obtaining clear solution; followed by dilution of clear solution in aqueous medium for obtaining desired concentration of homogeneous liquid drops.
Process for preparation of a gel based Phenothiazinium composition
For gel-based forms, phenothiazinium, phospholipid, nano or micronized gold or nano or micronized colloidal gold and/or the nano or micronized silver or nano or micronized colloidal silver and purified water are blended together followed by sonication. Further, at least one excipient such as guar gum, xanthan gum or gelatin are added, and mixed to achieve gel-based composition.
Embodiments of the method of preparation of compositions are further described herein by reference to the following examples by way of illustration only and should not be construed to limit the scope of the claims provided herewith. Various exemplary embodiments of the method are described hereunder.
Example 10: Phenothiazinium, phospholipid, nano or micronized gold or nano or micronized colloidal gold and/or the nano or micronized silver or nano or micronized colloidal silver and purified water were blended/mixed together; followed by addition of xanthan gum to the above mixture; blended or mixed to obtain the composition in a gel form.
Example 11: Phenothiazinium, phospholipid, nano or micronized gold or nano or micronized colloidal gold and/or the nano or micronized silver or nano or micronized colloidal silver and purified water were blended/mixed together for 10 to 20 minutes; followed by addition of beta cyclodextrin to the above mixture; blended or mixed for 15 to 30 minutes to obtain the composition in a gel form.
Example 12: Phenothiazinium, phospholipid, nano or micronized gold or nano or micronized colloidal gold and/or the nano or micronized silver or nano or micronized colloidal silver and purified water were blended/mixed together for 1 to 20 minutes; followed by addition of PEG fatty chains to the above mixture; blended or mixed for 15 to 30 minutes to obtain the composition in a gel form.
Example 13: 3g of Phenothiazinium was dissolved in of 600ml water, 25g propylene glycol was added and dissolved; methylcellulose (CMC) was added to 70 g of distilled water containing 0.3 g of an antioxidant, such as sodium metabisulphite and stirred to dissolve CMC; the mixture of Phenothiazinium, propylene glycol and water was mixed thoroughly with mixture of CMC and water and brought to a final weight of about 200 g followed by equilibrating the mixture at room temperature for about 6 to 18 hours.
Process for preparing a tablet composition comprising Phenothiazinium
The method for composing tablets includes mixing the obtained composition with a suitable excipient and grinding to obtain a semisolid mass. The obtained semisolid mass may further be processed by methods known in the field to obtain oral dosage forms. The method further includes drying at 55 to 65 degrees Celsius, preferably 60 degrees Celsius in a hot air oven followed by granulation and punching to obtain tablets. Granulation and tablet punching may be performed according to methods generally known in the field.
Treatment
Disclosed herein are embodiments of method for treatment of microbial infections. Embodiments herein also include a method for prevention of onset of microbial infections. In an embodiment disclosed herein, methods for the treatment of symptoms of microbial infections have been described. The methods, as disclosed herein may also be use in prevention and/or delay in development of complications related to microbial infection. The embodiments herein may also be instrumental in treating or preventing an allergy or the onset of bacterial and/or viral infections.
In an embodiment, the method comprises of administering a therapeutically effective amount of the disclosed composition to a subject in need thereof. Therapeutically effective amount, according to embodiments herein, refers to an amount of the composition that may be administered to a subject that is sufficient to achieve an intended purpose. Such amount, in many instances, may be determined in consultation with a physician or doctor.
In another embodiment, the method further comprises activating said composition by exposure to light energy. Light energy, according to embodiments herein, includes light suitable for activation of photosensitizers. It refers to light used in photodynamic therapy. In an embodiment, light energy includes low level light such as blue and red light wavelength, preferably of 610 nm to 670 nm. The exposure may be after or before administration of the composition. In various embodiments herein, the exposure of composition or the subject to light energy is capable of activating the composition and/or the intended therapeutic effect, for example stimulation of Cytochrome c Oxidase-Nitric Oxide activities. In an embodiment, the method further comprises exposing said subject to light energy. In another embodiment, the composition is exposed to the light energy before administration. In another embodiment, the exposure is after administration of the composition, preferably through a light emitting device. Light emitting devices are generally known and instrumental in phototherapy which may be used in order to emit light according to embodiments herein. In an embodiment, the activation is by exposing the subject to said light energy.
The term “subject”, as used herein includes any mammal, particularly human. It refers to any individual having or suspected of having microbial infection. It includes patients having infectious or non-infectious infections or diseases. It also includes any individual having complications or symptoms of microbial infections. It may also include cancer patients, especially requiring photodynamic therapy. It further includes individuals requiring photodynamic therapy, antimicrobial chemotherapy, etc. In an embodiment, it includes a patient having microbial infection. In another embodiment, it includes a patient having viral infection. In a specific embodiment, it includes patients having Corona virus disease such as COVID-19. In another embodiment, it includes patients exhibiting microbial infection with antimicrobial resistance, or antibiotic resistant strain.
Microbial infection, as referred to herein, includes infections by microbes such as bacteria, viruses, etc. Examples of bacteria include, but is not limited to, bacteria belonging to the family Staphylococcaceae such as S. argenteus, S. aureus, S. schweitzeri, S. simiae, S. auricularis, S. carnosus, S. condimenti, S. debuckii, S. massiliensis, S. piscifermentans, S. simulans, S. capitis, S. caprae, S. epidermidis, S. saccharolyticus, S. borealis, S. devriesei, S. haemolyticus, S. hominis, S. agnetis, S. chromogenes, S. cornubiensis, S. felis, S. delphini, S. hyicus, S. intermedius, S. lutrae, S. microti, S. muscae, S. pseudintermedius, S. rostri, S. schleiferi, S. lugdunensis, S. arlettae, S. caeli, S. cohnii, S. equorum, S. gallinarum, S. kloosii, S. leei, S. nepalensis, S. saprophyticus, S. succinus, S. xylosus, S. sciuri group – S. fleurettii, S. lentus, S. sciuri, S. stepanovicii, S. vitulinus, S. simulans, S. pasteuri, S. warneri, and S. caseolyticus;S. aureus subsp. Aureus, S. aureus subsp. Anaerobius, S. capitis subsp. Capitis, S. capitis subsp. Urealyticus, S. carnosus subsp. Carnosus, S. carnosus subsp. Utilis, S. cohnii subsp. Cohnii, S. cohnii subsp. Urealyticus, S. equorum subsp. Equorum, S. equorum subsp. Linens, S. hominis subsp. Hominis, S.ominis subsp. Novobiosepticus, S petrasii subsp. Croceilyticus, S petrasii subsp. Jettensis, S petrasii subsp. Petrasii, S petrasii subsp. Pragensis, S. saprophyticus subsp. Bovis, S. saprophyticus subsp. Saprophyticus, S. schleiferi subsp. Coagulans, S. schleiferi subsp. Schleiferi, S. sciuri subsp. Carnaticus, S. sciuri subsp. Rodentium, S. sciuri subsp. Sciuri, S. succinus subsp. Casei, and S. succinus subsp. Succinus.
Examples of virus include, but is not limited to, herpes simplex virus 1, herpes simplex virus 2, herpes zoster (shingles), human herpes virus 1, human virus 2, human herpes virus 3, Epstein-Barr virus or human herpes virus 4, human cytomegalovirus or human herpes virus 5, human herpes virus 6A, human herpes virus 6B, human herpes virus 7, Kaposi sarcoma-associated herpes virus or human herpes virus 8, smallpox virus, vaccinia virus, cowpox virus, monkeypox virus, rabbitpox virus, orf virus, pseudocowpox, bovine papular stomatitis virus, tanapox virus, yaba monkey tumor virus, molluscum contagiosum virus, hepatitis virus B, African swine fever virus, west nile virus, dengue virus, tick-borne encephalitis virus, yellow fever virus, zika virus, palm creek virus, parramatta river virus, yellow fever virus, alphavirus, togavirus, coronaviruses, hepatitis A virus, hepatitis B virus, hepatitis C virus, hepatitis D virus, influenza virus, alpha influenzavirus, beta influenzavirus, delta influenzavirus, gamma influenzavirus, isavirus, thogotovirus, and quaranjavirus, paramoxyvirus, rhabdovirus, bunyavirus, human immunodeficiency virus-1 (HIV-1), human immunodeficiency virus-2 (HIV-2), and human T-lymphotropic virus (HTLV). Ina an embodiment, the virus is Coronavirus. In an embodiment, the method is used in treating coronavirus disease. In an embodiment, the method is used in alleviating complication and symptoms of coronavirus disease.
In an embodiment, the composition can be used for the treatment of different infections but not limited to urinary tract infections, oral infections, gastrointestinal microbial infections etc.
Zwitterionic polymer-lipid was self-assembled into liposomes and encapsulate methylene blue (MB-liposome). MB liposome has high stability and fast intracellular uptake. It also has higher in vitro ROS generation ability than that of free methylene blue (MB). With the features found, MB-liposome has the potential of being an effective PDT Nano agent for antimicrobial therapy.
Referring now to the figures, Fig. 1 is an illustration of the cellular mechanism of action of photosensitizer. Fig. 2 are graphs depicting fluorescence intensity and rate of fluorescence of MB conjugated with gold nanoparticles. Fig. 3 depicts a graph showing increment in fluorescence intensity by Phenothiazinium category molecule. Fig. 4 are images from TEM, SEM, and Confocal Laser Scanning Microscopy (CLSM) analysis showing photo-cytotoxicity by phenothiazinium category molecule. ROS probes and PCA analysis showed the cytoplasmic O2 is antimicrobial agent. The Methylene Blue Gold Nanoparticle didn’t show any photo-cytotoxicity against mammalian cells. Fig. 5 depicts TEM image of Methylene blue-liposomes and a graph showing Dynamic light scattering (DLS) measurement of MB-liposomes. Fig. 6 are UV-Vis’s spectral profiles of free MB, MB-liposomes, and MB-liposomes with Nano Gold & silver 4.5mcg & 6.5mcg respectively, graph depicting stability of composition - hydrodynamic diameter of MB-liposomes over 14 days. Fig. 7 are TEM images of Phenothiazinium category molecule and a graph showing nano particle size distribution of 60 nm to 140 nm and its intensity of absorbance. Fig. 8 are images depicting liposome entrapped Phenothiazinium category molecule, Phenothiazinium category molecule - liposome after removal of coating, and enzymatic treatment of Phenothiazinium category molecule – liposome. Fig. 9 are graph showing 24-h cell viability (by MTT assay) of free MB and MB-liposomes and Distilled Water (DI) as control at different concentrations with dark treatment and photodynamic therapy (PDT) treatment, while the images depict free MB and MB-liposomes at 8µm concentration and Distilled Water (DI) with dark treatment and photodynamic therapy (PDT) treatment. Fig. 10 depicts SEM images of Curcumin nanoparticles and silver & gold nanoparticles. Fig. 11 depicts SEM images of colloidal gold nanorods. Fig. 12 are images depicting Phenothiazinium category molecule, Phenothiazinium category molecule liposomal form, oxidation rate, Phenothiazinium category molecule liposomal form after sonification. Fig. 13 is a pictorial representation of blue light excitation of Liposomal - MB and red light excitation of Liposomal – MB respectively. Under blue light, Liposomal - MB is excited and emits red fluorescence. Its detection can guide the surgical resection of the fluorescent tissues. By exciting MB with red light, reactive oxygen species such as singlet O2 are formed through photochemical reactions and energy transfer. These cause oxidative damage to vital cellular components such as lipids, proteins and nucleic acids, culminating in massive tumor cell death. Fig. 14 is a graph showing X ray diffraction pattern of Colloidal silver nanoparticles. Fig. 15 is a graph showing X ray diffraction pattern of pure curcumin. A solution of 5 mM methylene blue in D2O was irradiated overnight at 633 nm and ESI analyses were performed. Fig. 16 depicts ESI mass spectrum of methylene blue before and after overnight irradiation respectively. Fig. 17 depicts graph showing nano silver mass spectrometry pattern. Fig. 18 depicts Mass spectra Pattern of Curcumin; wherein 18(a) is mass spectra of curcumin; 18(b) is mass spectra of hydroxylated curcumin, while 18(c) is mass spectra of daughter ion of curcumin. Fig. 19 depicts graphs showing absorption spectra of colloidal gold ion of 5 nm and 20 nm and colloidal gold with low molecular complex respectively. Fig. 20 is a schematic overview of photo inactivation of multidrug resistant microbes by monomeric methylene blue conjugated gold nanoparticles. Fig. 21 is a schematic representation depicting tailoring photosensitive ROS for advance photodynamic therapy while the lower schematic representation is a Jablonski diagram showing the photochemical mechanism. Fig. 22 is a schematic representation of Tissue penetration depths of various wavelengths. Fig. 23 is a graph with the central image shows photospectrometric data measured from penetration through a human hand in vivo Based on the computer‐derived trace on that part of the figure, the upper section illustrates relative penetration of selected wavelengths into the skin. Coupled with these, the lower section shows the absorption spectra of some biological chromophores, or targets, namely melanin, blood and water. Note the wavelength selectivity in these chromophores, and how that helps to determine the depth of penetration of different wavelengths into a living target as well as determining the target itself. Fig. 24 is a schematic representation of general action mechanism of photodynamic applications on viruses. The PDI of viruses shares the general action mechanism of photodynamic applications: the irradiation of a dye with light and the subsequent generation of ROS which are the effective phototoxic agents damaging virus targets by reacting with viral nucleic acids, lipids and proteins.
The foregoing description of the specific embodiments will so fully reveal the general nature of the embodiments herein that others can, by applying current knowledge, readily modify and/or adapt for various applications such specific embodiments without departing from the generic concept, and, therefore, such adaptations and modifications should and are intended to be comprehended within the meaning and range of equivalents of the disclosed embodiments. It is to be understood that the phraseology or terminology employed herein is for the purpose of description and not of limitation. Therefore, while the embodiments herein have been described in terms of preferred embodiments, those skilled in the art will recognize that the embodiments herein can be practiced with modification within the spirit and scope of the embodiments as described herein.