Description:FIELD OF THE INVENTION
The present invention relates to a pharmaceutical composition of chlorine for treatment infectious diseases. More particularly, the invention relates to administering effective concentration of chlorine for the treatment of infection disease. The present invention also provides a method for the management of infectious diseases by administering pharmaceutically effective amount of chlorine by different route of administration.
BACKGROUND OF THE INVENTION
The infectious diseases are caused due to harmful pathogen that gets into body from outside. The pathogens are broadly classified as bacteria, virus, parasites and fungi etc. The treatment for infectious diseases is varying based on the type of pathogen involved. The infectious diseases which are caused due to bacteria are generally treated with antibiotics, whereas for viral infections antiviral agents are used. Mostly, it is preferable to use preventive measures to control the spread of infectious diseases. However, disinfectant plays a key role in treating and preventing the infection caused due to pathogen.
It is discovered that each disinfectant has totally different effects, attacking one or several of the virus’ functions, bacterial site etc. Even though the outcome is the same, the eradication methods are different. Ozone, ultraviolet irradiation, liquid chlorine, chlorine dioxide, and sodium hypochlorite disinfections are commonly used technologies for disinfection. Using the correct disinfectant is an important part of preventing and reducing the spread of illnesses. Isopropanol or Ethanol (Alcohol), Quaternary Ammonium Compounds, Sodium Hypochlorite (Bleach), Hydrogen Peroxide are some common disinfectants which kills viruses, bacteria as well as fungi. Chlorine is a kind of strong oxidizer, which is one of the most early used disinfection methods.
US6333054 discloses topic hydrogel disinfectant composition comprising active chlorine.
Various non-patent literatures disclosed the Effects of a Low Concentration hypochlorous acid (HOCl). Hyun Jik Kim et al (Laryngoscope 118: October 2008) disclose Effects of a Low Concentration hypochlorous acid nasal irrigation solution on bacteria, fungi, and viruses. This literature disclosed the virucidal effects of HOCl and used the human influenza virus to challenge the cells.
Thus, the inventors of the present invention have successfully addressed the existing drawbacks and formulated pharmaceutical composition of chlorine for treatment infectious diseases.
OBJECTIVE OF THE INVENTION
An object of the present disclosure is to provide a pharmaceutical composition of chlorine for treatment infectious diseases.
Another object of the present disclosure is to provide a pharmaceutical composition with the effective concentration of chlorine for the treatment of infection disease.
Another object of the present disclosure is to provide an effective formulation of chlorine for treatment of treatment of infection disease.
Yet another object of the present disclosure is to provide a method for administration of the pharmaceutical composition of chlorine for treatment of infection disease.
SUMMARY OF THE INVENTION
The present disclosure provides the pharmaceutical composition comprising
- aqueous chlorine solution ; and
- optionally stabilizer;
wherein concentration of chlorine is 0.5 mg to 10 mg.
In one embodiment, the aqueous chlorine solution is prepared by dissolving an effective amount of chlorine in purified water and optionally adding stabilizing agent.
In another embodiment, wherein composition is administered by inhalation or parenteral route.
In another embodiment, wherein composition is administered by intramuscular route or intravenous route
In another embodiment, wherein composition is administered by inhalation via nose inhaler or mouthpiece as gas, mixture of gas, liquid, mist, spray, aerosol or steam.
In another embodiment, wherein composition is further administered by dilution with medium; wherein dilution medium is selected from group consisting of compressed air, inert carrier gas or oxygen or mixture thereof.
In another embodiment, wherein composition is further administered by injection or through intravenous route.
In another embodiment, wherein administration through intravenous route is with or without sodium chloride fluid of aqueous chlorine for the treatment of infection disease in human and animal.
In another embodiment, the method of treating the infectious diseases by administering to the subject the pharmaceutical composition and pharmaceutically acceptable excipient.
In another embodiment, wherein infectious diseases are the diseases caused due to the bacterial infections, viral infections and fungal infections.
While several embodiments have been described in detail, it will be apparent to those skilled in the art that the disclosed embodiments may be modified. Therefore, the foregoing description is to be considered exemplary rather than limiting.
BRIEF DESCRIPTION OF THE DRAWING
The following figures are illustrative of particular examples for enabling embodiments of devices and methods of the present disclosure, are descriptive of some of the embodiments and are not intended to limit the scope of the disclosure. The figures are not to scale (unless so stated) and are intended for use in conjunction with the explanations in the following detailed description. Wherever applicable, the words and phrases used herein should be understood and interpreted to have a meaning consistent with the understanding of those words and phrases by those skilled in the relevant art. Persons skilled in the art will appreciate that elements in the figures are illustrated for simplicity and clarity and may have not been drawn to scale. For example, the dimensions of some of the elements in the figure may be exaggerated relative to other elements to help to improve understanding of various exemplary embodiments of the present disclosure. Throughout the drawings, it should be noted that like reference numbers are used to depict the same or similar elements, features, and structures.
Figure 1: Illustrates mechanism of action of liquid composition disclosed in the present invention.
Figure 2: Illustrates the (A) LifeViroTreat unit vial,(B) method of application by nebulizer and (C) LifeViroTreat pilot batch for clinical testing.
DESCRIPTION
In the description that follows, a number of terms are used, the following definitions are provided to facilitate understanding of various aspects of the disclosure. Use of examples in the specification, including examples of terms, is for illustrative purposes only and is not intended to limit the scope and meaning of the embodiments of the invention herein. Numeric ranges are inclusive of the numbers defining the range. In the specification, the word “comprising” is used as an open-ended term, substantially equivalent to the phrase “including, but not limited to,” and the word “comprises” has a corresponding meaning.
The terms and words used in the following description are not limited to the bibliographical meanings, but, are merely used to enable a clear and consistent understanding of the disclosure. Accordingly, it should be apparent to those skilled in the art that the following description of exemplary embodiments of the present disclosure are provided for illustration purpose only and not for the purpose of limiting the disclosure as defined by the appended claims and their equivalents.
Features that are described and/or illustrated with respect to one embodiment may be used in the same way or in a similar way in one or more other embodiments and/or in combination with or instead of the features of the other embodiments.
The therapeutically effective amount administered to the individual e.g., a mammal, particularly a human, in the context of the present invention should be sufficient to affect a therapeutic or prophylactic response in the individual over a reasonable time frame. The dose can be readily determined using methods that are well known in the art. One skilled in the art will recognize that the specific dosage level for any particular individual will depend upon a variety of potentially therapeutically relevant factors.
The term "subject" includes mammals, which can alternatively be used as ‘Individual’ (especially humans) and other animals, such as domestic animals (e.g., household pets including cats and dogs) and non-domestic animals (such as wildlife).
The term "Treating" or "treatment" of a disease includes (1) preventing the disease from occurring in subject that may be predisposed to the disease but does not yet experience or display symptoms of the disease, (2) inhibiting the disease, i.e. arresting its development, or (3) relieving the disease, i.e. causing regression of the disease.
The present invention is further described by reference to the following examples, which are illustrative only and not limiting of the claimed invention.
Examples:
Following Examples 1 to 6 describe the process of preparing pharmaceutical composition (LifeViroTreat)
Example-1: Preparation of Ampules
The chlorine (0.5 mg) is dissolved in the WFI grade water (10 ml) in presence of stabilizers to form a chlorine gas solution at 0-10°C.
Example-2: Preparation of Respule
The chlorine (2.5mg) is dissolved in the WFI grade water (10 ml) in presence of stabilizers to form a chlorine gas solution at 0-10°C.
Example-3: Preparation of Respule
The chlorine (5 mg) is dissolved in the WFI grade water (1000 ml) in presence of stabilizers to form a chlorine gas solution at 0-10°C.
Example-4: Preparation of Respule
The chlorine (8 mg) is dissolved in the WFI grade water (1000 ml) in presence of stabilizers to form a chlorine gas solution at 0-10°C.
Example-5: Preparation of Respule
The chlorine (10 mg) is dissolved in the WFI grade water (1000 ml) in presence of stabilizers to form a chlorine gas solution at 0-10°C.
Example-6: Preparation of Vials
Aqueous chlorine solution is prepared by simple solubilization method. An amount of 1000 mg chlorine dissolved in 1000 mL of triple distilled water along with stabilizer and stirred for 15 minutes to get a uniform solution. Aqueous chlorine solution is sterilized by filtration method and passed through 0.22µ filter. The sterilized aqueous chlorine solution filled in pre-sterilized vials and aseptically sealed with closure (Figure 2 A). Filled vials are further packed in primary followed by secondary carton and stored at USP cool temperature.
(II) Stability studies
Stability studies were carried out. The composition described hereinabove is stable for 1 year and to be stored at 2 to 8° C in amber color glass container.
(III) Safety and toxicological studies
Preclinical studies of Lifevirotreat composition were studies as to determine the safety of the composition. The Clinical trials studies of the present invention are carried out by Panexell clinical lab Pvt. Ltd.
Pre-clinical studies were performed by administering a multiple inhalation doses to rodent rats and non-rodents rabbits (Table 2), followed by observation period of 14 days, 3 female animals per dose level were used in this study as described in the OECD guidelines for testing of chemicals. Animals were kept in animal restrainer and connected with nebulizer. Nebulizer chamber was filled before starting the experiment with aqueous chlorine formulation (1 mg/m3) for 15 minutes (LifeViroTreat, 10 ml glass vial). Animals were exposed to the aqueous chlorine formulation for 15 minutes and for 6 and 12 times in a day. Animals were assessed for their mortality and morbidity. After blood collection animals were sacrificed and subjected to gross necropsy, which included an careful examination of the external surface of body, all orifices, and the cranial, thoracic and abdominal cavities and their contents. Once gross necropsy is done the organs like brain, lung, liver, heart, adrenal gland, kidney, uterus and ovaries were surgically removed, weighed and stored. Lung tissues were studied for further histopathological studies.
Table 1 Experimental detail for preforming safety and toxicological studies for LifeViroTreat Composition
AnimalModel Dose Frequency of dose No. of Animals Sex Route of administration

Rat Air control - 3

Female

Inhalation through Nebulizer

5Times
(4.18mg/kg) LD2
(Every4hourfor 3days)
3
LD4
(Every2hourfor3days)
3

10Times
(8.37mg/kg) HD2
(Everyfourhourfor5days)

3
HD4
(Every2hourfor 3days)
3

Rabbit
AirControl -
3

Female

Inhalation through Nebulizer

5Times
(2.09mg/kg) LD2
(Every4hourfor3days)
3
LD4
(Every2hourfor3days)
3

10Times
(4.19mg/kg) HD2
Everyfourhourfor5days
3
HD4
(Everyfourhourfor5days)

3
Moreover, after the exposure period on14day biochemical parameters (Table 2 & table 3) and hematological (Table 4 & Table 5) were investigated. Animals were evaluated for anxiety, motor activity and other behavioral changes.
Table 2 Effects of LifeViroTreat composition by inhalation route on some biochemical parameters in the acute toxicity study in rats

PARAMETERS Treatment Groups Reference
Values
Control Group 5Times
(4.18mg/kg) 10Times
(8.37mg/kg)
Air Control LD2
(Every4hourfor3days) LD4
(Every 2 hour for3days) HD2
(Every4hour
for3days) HD4
(Every2hour for3days)
ALB(g/dL) 3.82± 0.27 3.93± 0.21 3.81±0.31 3.67± 0.19 3.42±0.44 3.4– 4.8
ALP(U/L) 217.33±18.15 230.00 ± 50.74 209.33± 14.72 178.33± 33.61 162.67 ± 7.02 62-237
ALT(U/L) 54.86 ± 7.29 45.90±12.64 52.80±4.00 53.50± 4.93 51.00±1.25 18-76
AST(U/L) 95.63 ± 12.47 100.07 ± 15.59 125.47± 20.10 116.67± 12.15 102.97 ± 17.39 74-143
BIL (mg/dL) 0.10± 0.00 0.10± 0.00 0.10±0.00 0.10± 0.00 0.10±0.00 0.05-0.15
CA(mg/dL) 10.38 ± 0.61 10.93±0.67 10.00±1.75 9.23± 1.10 9.17±2.11 9.5-11.5
CHO(mg/dL) 51.10 ± 6.27 59.77±2.67 55.23±6.82 44.83± 5.14 50.87±4.35 37-85
CREJ(mg/dL) 0.36± 0.05 0.32± 0.02 0.30±0.01 0.32± 0.07 0.31±0.02 0.2-0.5
PHOS(mg/dL) 6.54± 1.40 7.57 ± 1.58 7.07 ± 1.72 7.03± 1.59 8.33±1.56 5.58-10.41
TP(g/dL) 6.30± 0.54 6.64 ±0.84 7.04± 0.29 6.81± 0.45 6.67±0.06 5.2-7.1
UREA(mg/dL) 15.60 ± 1.62 17.97± 3.47 20.40± 1.21 19.10 ± 4.20 22.17 ± 2.35 12.3-24.6
GLU(mg/dL) 144.33±15.28 133.00± 10.58 132.33±14.64 120.00± 12.77 142.33± 17.24 70-208
Note: Each value represents the mean± standard deviation(n=3)

Table 3 Effects of LifeViroTreat composition by inhalation route on some biochemical parameters in the acute toxicity study in rabbits

PARAMETERS Treatment Groups ReferenceValues
Control Group 5Times
(4.18mg/kg) 10Times
(8.37mg/kg)
Only Air Group I(Every4hour for 3days) GroupII (Every2hour for3 days) GroupIII
(Every4hour for 3days) GroupIV (Every2hourfor 3days)
ALB (g/dL) 34.03 ± 6.09 3.93± 0.05 3.81±0.31 3.67±0.19 3.42 ±0.44 23-49
ALP(U/L) 204.44±17.64 196.67±102.02 259.33±32.52 278.33± 33.61 229.33± 51.47 44-402
ALT(U/L) 56.15 ± 7.29 45.90±12.64 52.80±4.00 53.50±4.93 51.00± 1.25 34-146
AST (U/L) 22.36 ± 4.63 138.40±18.40* 107.37± 5.41 106.70 ±1.23 103.97± 2.10 7.5-39.7
BIL(mg/dL) 0.10± 0.00 0.10± 0.00 0.10±0.00 0.10±0.00 0.10 ±0.00 0.019-0.2
CA (mg/dL) 10.90 ± 1.99 5.93±0.67 5.00±0.26 5.57± 0.45 5.00 ±0.17 9.22-13.63
CHO (mg/dL) 53.46 ± 5.04 59.77±2.67 55.23±6.82 44.83±5.14 50.87± 4.35 30-65
CREJ(mg/dL) 0.81± 0.22 0.32± 0.02 0.30±0.01 0.32±0.07 0.31 ±0.02 0.5-2.6
PHOS(mg/dL) 5.12± 0.13 6.23± 0.06 5.03±0.40 5.37±0.49 4.67 ±0.49 4-6
TP(g/dL) 60.62 ± 8.64 7.09± 0.21 7.04±0.29 6.81±0.45 6.67 ±0.06 49-79
UREA (mg/dL) 48.04 ± 9.41 34.63±3.61 34.07±4.70 33.17±2.37 33.50± 0.75 25.48-71.41
GLU(mg/dL) 150.67±11.06 136.67±9.28 143.33±13.01# 132.33 ±11.59 140.00 ±11.00 89-150
Note: Each value are presents the mean ± standard deviation(n=3)
ALB2:Albumin,ALP:Alkalinephosphatase, ALT: Alanine Aminotransferase, AST:AspartateAminotransferase,BILT2: TotalBilirubin,CA2:Calcium, CHOL: Cholesterol,CREJ: Creatinine,PHOS: Phosphorous,TP:Total protein, UREL: Urealevel, GLU: Glucose
No mortality and morbidity were observed in any of the animals administered with the test item (Table 6). All the values were in normal range as per reference values and no significant variation was observed in any parameter in all treated group as compared to normal control(Air control) Group. In all the steps, animals were in somnolence condition with decreased motor activity. None of the animals exhibited gross lesions related to test item administration. Increase in body weight was observed in all the treated animals at the end of the experiment. Based on the results obtained, it is concluded that, LifeViroTreat at was found to be safe. , Claims:WE CLAIM
1. A pharmaceutical composition comprising
- aqueous chlorine solution ; and
- optionally stabilizer;
wherein concentration of chlorine is 0.5 mg to 10 mg.
2. The pharmaceutical composition as claimed in claim 1, wherein aqueous chlorine solution prepared by dissolving an effective amount of chlorine in purified water and optionally adding stabilizing agent.
3. The pharmaceutical composition as claimed in claim 1, wherein composition is administered by inhalation or through parenteral route.
4. The pharmaceutical composition as claimed in claim 1, wherein composition is administered by inhalation via nose inhaler or mouthpiece as gas, mixture of gas, liquid, mist, spray, aerosol or steam.
5. The pharmaceutical composition as claimed in claim 1, wherein composition is further administered by dilution with medium; wherein dilution medium is selected from group consisting of compressed air, inert carrier gas or oxygen or mixture thereof.
6. The pharmaceutical composition as claimed in claim 3, wherein composition is further administered by injection or through intravenous route.
7. The pharmaceutical composition as claimed in claim 6, wherein administration through intravenous route is with or without sodium chloride fluid.
8. The method of treating the infectious diseases by administering to the subject the pharmaceutical composition as claimed in claim 1 and pharmaceutically acceptable excipient.
9. The method as claimed in claim 1, wherein infectious diseases are the diseases caused due to the bacterial infections, viral infections and fungal infections.