DESC:FIELD OF THE INVENTION
This invention comprises Sugar- free dry syrup made up of with the Synergy effect of Natural botanical ingredients and its isolated form - Extract. The present disclosure relates method development of antiviral & immunomodulator dry syrup. In particular, the present disclosure relates to the polyherbal composition comprising of Trachyspermum Ammi extract, Glycyrrhiza Glabera extract, Ocimum Sanctum extract, Piper longum extract, Iris Germanica extract, Zingiber Officinale extract, Solanum Nigrum extract, Piper betle extract, Piper nirgum extract, Syzygium aromaticum extract, Cinnamomum verum extract, Curcuma Longa extract, Adhatoda vasaca extract to form sugar free dry syrup. The present disclosure further relates to the method of preparing the said polyherbal mixture.

BACKGROUND OF THE INVENTION
Herbal ingredients play an important role in respiratory disease. Stability is main drawback in herbal syrup and hence high concentration of antioxidant and preservative should be added and it is not safe for longer period of time. To overcome this problem, present invention compliance with synergy phytoconstituents based Dry Syrup formulation and a method for preparation thereof for providing treatment in chronic respiratory disorders such as cold, cough, allergic, asthma, seasonal allergic rhinitis, pharyngitis, laryngitis, bronchitis and the like and which is nonalcoholic, non-sedating and chemical free in nature.

In oral drug delivery, Syrup is convenient, inexpensive, and good for a pediatric patient. In the allopathy, trend of taste- masked syrup, dry syrup increased due to the palatability and unpleasant odour of API. Sugar base or artificial sweeteners can’t able to masked unpleasant bitterness of API or Active ingredients either Herbal or Phytoconstituents. In ayurvedic (Herbal) industry, the syrup concept is there but has certain drawbacks like stability, palatability, solubility, sedimentation, and base compatibility.

To overcome this drawback, the dry syrup concept is emerging and hence we invent technology of synergy mixture of 13 phytoconstituents and its synergy effects in different viral symptoms, especially in cough and cold. Stability, Photostability, Sedimentation rate viscosity, palatability, and aqueous solubility maintains by unique granulation techniques. There is no incorporation of flavors, preservatives, solubilizers, sugar or sugar derivatives.

KR102538436B1 discloses novel macrocyclic peptides that inhibit PD-1/PD-L1 and PD-L1/CD80 protein/protein interactions and are thus useful for the amelioration of various diseases including cancer and infectious diseases.

CN110997698B discloses novel macrocyclic peptides that inhibit PD-1/PD-L1 and PD-L1/CD80 protein/protein interactions and are therefore useful for ameliorating various diseases, including cancer and infectious diseases.

CA2980173C discloses Phenyl carboxylate/acrylate compounds having unique antiviral properties found in mushroom mycelium and their analogs are extracted, concentrated, isolated, synthesized or manufactured to create compositions useful in treating, ameliorating, mitigating, alleviating, reducing or curing a pathogenic virus infection such as human papilloma virus. More particularly, such compositions can include one or more of syringic acid, trans-cinnamic acid, trans-ferulic acid, salts thereof or esters thereof. The compositions can be formulated into dosage forms comprising sprays, capsules, tablets, elixirs, emulsions, lozenges, suspensions, syrups, pills, lotions, epidermal patches, suppositories, inhalers, or injectables.

WO2021213288A1 discloses antiviral application of a nucleoside analog. Specifically, the present invention relates to uses of the nucleoside analog and a pharmaceutical composition thereof as: (a) inhibitors for inhibiting the replication of coronaviruses, influenza viruses, respiratory syncytial viruses, flaviviridae viruses, filoviridae viruses and/or porcine epidemic diarrhea virus (PEDV); and/or (b) medicines for treating and/or preventing and mitigating diseases caused by coronavirus, influenza virus, respiratory syncytial virus, flaviviridae virus, filoviridae virus and/or porcine epidemic diarrhea virus (PEDV) infections. The nucleoside analog according to the present invention may treat and/or prevent and mitigate respiratory infection, pneumonia (COVID-19) and other related diseases caused by the 2019 novel coronavirus infection.

International Journal Of Medical Science And Clinical Research Studies (Vol. 2 No. 2 (2022): Volume 02 Issue 02 February 2022) A Randomized, Open Labeled Clinical Survey To Evaluate The Anti-Viral, Anti-Inflammatory and Immune Modulator Role of Polyherbal Combinations in Viral Infections of Respiratory Tract (Naram, S., Mahajan, D., & Parekh, H. (2022)) discloses Cough is the common reflex produced for upper respiratory tract infections (URTI), however, a cough can also be a symptom of other hidden conditions like asthma or other lung diseases. The immune modulation with Ayurvedic formulations as possible therapeutic measures is the need of time. Ancient Indian medicinal system of Ayurveda has a wide scope for treating many diseases by the theory of Rasayana. Rasayana in other terms are called as preparations from plant or herbal sources which have immunomodulatory properties. As this is a Pilot study each participant is supplied with the Swaswin D Vyro (Virofight) 625 mg two tablets twice a day, Swaswin Asthaloc 600 mg two tablets twice a day, Syrup Swaswin Kaphano 5 ml twice a day after food with lukewarm water at each visit.

Elsevier, Antiviral and Immunomodulatory Drugs (Sykes, J. E., & Papich, M. G. (2014) discloses The purpose of this chapter is to describe the mechanisms of action, spectrum of activity, and adverse effects of the major antiviral and immunomodulatory drugs that have exhibited utility or have potential for treatment of companion animal infectious diseases. An enormous number of different compounds have been considered or evaluated in vitro and in vivo with variable success.

OBJECTIVE OF INVENTION
Various Ayurvedic syrups are available in the market for coughs and colds, respiratory diseases, and many more. It contains botanical ingredients either with raw form or standardized extracts mixed with the sugar- containing aqueous bases. Sugar base is around than 50-90% with a very low concentration of herbs or its extracts due to its palatability. Water is a big source for contamination and impurity hence preservatives like methyl paraben, propyl paraben should be incorporated for its stability. In some liquid syrup, sedimentation problem is also there due to poor viscosity and non-uniformity of particle size and solubility. In some liquid syrup contains herbs or botanical ingredients get fermented due to its poor stability or photodegradation because many herbs and phytochemicals are photolabile in the presence of water.

To overcome all problems, we invent dry syrup formulation. Its sugar- free, preservative free, stable for 3 years as per ICH guidelines, good palatability, good water solubility, and Photostability free with a high concentration of active ingredients (Synergy Phytoconstituents) derived from herbs. It is proven for antiviral activity on specific SARS-Cov-2 viruses from the department of biotechnology. In human clinical trials, it proved antiviral effects by reducing respiratory symptoms like cough, cold, shortness of breathing, spo2, with improvement in body ache and fever.

SUMMARY OF THE INVENTION
A polyherbal blend of sugar free dry syrup composition comprising of Trachyspermum Ammi extract, Glycyrrhiza Glabera extract, Ocimum Sanctum extract, Piper longum extract, Iris Germanica extract, Zingiber Officinale extract, Solanum Nigrum extract, Piper betle extract, Piper nirgum extract, Syzygium aromaticum extract, Cinnamomum verum extract, Curcuma Longa extract, Adhatoda vasaca extract to form sugar free dry syrup

The present disclosure further relates to the method of preparing the said polyherbal mixture.

The present invention is Taste masked, Stable, Fast dissolving, Excipientless, Sugar-free, Preservative free, compatible Dry syrup made up of with Phytoconstituents and its blend.

Adding raw extract of Trachyspermum Ammi extract, Glycyrrhiza Glabera extract, Ocimum Sanctum extract, Piper longum extract, Iris Germanica extract, Zingiber Officinale extract, Solanum Nigrum extract, Piper betle extract, Piper nirgum extract, Syzygium aromaticum extract, Cinnamomum verum extract, Curcuma Longa extract, Adhatoda vasaca extract in a beaker and mixing them well and converting the same into syrup. Dry all blend of Phytoconstituents at 40-55°C in tray dryer or fluidized bed dryer for 30-60 min. Pulverized it in sieve number 80-100. Check flowability of individual as per free flow compliance and mixed all in synergy form. Continue mixing of all improvised granules for 30-45 min and then add natural blend of Mentha Spicata extract 4-8% and again mix for 20-30 minutes. At last mixed Glycyrrhiza Glabera with optimized concentration in above blend and mixed it for 15-20 min. Viscosity adjusted with Natural gum of Phytoconstituents blend.

DETAILED DESCRIPTION OF THE INVENTION:
Detailed Description of the Invention While this specification concludes with claims particularly pointing out and distinctly claiming that, which is regarded as the invention, it is anticipated that the invention can be more readily understood through reading the following detailed description of the invention and study of the included examples.
The following is a detailed description of embodiments of the present disclosure. The embodiments are in such detail as to clearly communicate the disclosure. However, the amount of detail offered is not intended to limit the anticipated variations of embodiments; on the contrary, the intention is to cover all modifications, equivalents, and alternatives falling within the spirit and scope of the present disclosure as defined by the appended claims.

Unless the context requires otherwise, throughout the specification which follow, the word “comprise” and variations thereof, such as, “comprises” and “comprising” are to be construed in an open, inclusive sense that is as “including, but not limited to.”

Reference throughout this specification to “one embodiment” or “an embodiment” means that a particular feature, structure or characteristic described in connection with the embodiment is included in at least one embodiment. Thus, the appearances of the phrases “in one embodiment” or “in an embodiment” in various places throughout this specification are not necessarily all referring to the same embodiment. Furthermore, the particular features, structures, or characteristics may be combined in any suitable manner in one or more embodiments.

The headings and abstract of the invention provided herein are for convenience only and do not interpret the scope or meaning of the embodiments.
Various terms are used herein. To the extent a term used in a claim is not defined below, it should be given the broadest definition persons in the pertinent art have given that term as reflected in printed publications and issued patents at the time of.
The present invention relates to a Phyto Pharmaceutical formulation containing a mixture of specified herbal phytoconstituents and a method for preparation thereof for providing treatment in chronic respiratory disorders such as cold, cough, allergic asthma, seasonal allergic rhinitis, pharyngitis, laryngitis, Bronchitis and the like and which is nonalcoholic, non-sedating and non-freezing and super soluble in nature. Further, the process for the preparation of Phyto Synergy composition of the present invention does not involve the use of pharmaceutically unacceptable and hazardous organic solvents. The process for preparing this composition of the present invention comprises procuring, cleaning, grading of specified herbal extraction as per the standard specification, and design granulation to improve poor palatability and micromeritics property for high disintegrating power and pulverizing separately to form the fine free flow powder.
"Antiviral & Immunomodulator Dry Syrup" appears to be a pharmaceutical product, likely a combination drug aimed at combating viral infections while also modulating the immune response. Unfortunately, without specific details or a reference to a particular brand or manufacturer, it's challenging to provide detailed information about this specific product. However, I can offer some general insights into what such a product might entail:
Antiviral Agents: The syrup likely contains compounds or medications with antiviral properties. These agents work by inhibiting the replication of viruses, thus helping to reduce the severity and duration of viral infections. Common antiviral agents include acyclovir, oseltamivir, and various interferons.
Immunomodulators: Immunomodulators are substances that help regulate the immune response. In the context of an antiviral syrup, immunomodulators may be included to enhance the body's immune defences against viral infections. These could include cytokines, immune stimulants, or herbal extracts with immunomodulatory effects.
The process of manufacturing of herbal extracts is as follows:
1. Individual Phytoconstituent as per mentioned specification cross check by suitable analytical technique.
2. Except Glycyrrhiza Glabera Individual extract reprocesses with granulation to improve palatability and micromeritics property. Granulation blend process are as follow.
(a) Synergy form of Curcumin mixed with Black piper, Lavang and Saponin blend of Liquorice for Anti-inflammatory effect by improve its poor characteristics.
(b) Synergy form of Ajwain, Ginger, Cinnamon mixed for synergy bronchodilation and Antihistaminic effect.
(c) Synergy form of Betel leaf, Kakamachi and Lindipiper mixed for cough, cold and expectorants
(d) Synergy blend of Puskarmool, Tulsi and Vasaka mixed for its Antiviral, Anti-bacterial activity
3. Dry all blend of Phytoconstituents at 40-55 0C in a tray dryer or fluidized bed dryer for 30-60 min.
4. Pulverized it in sieve numbers 80-100.
5. Check the flowability of the individual as per free flow compliance and mixed all in synergy form.
6. Continue mixing of all improvised granules for 30-45 min and then add a natural blend of Mentha Spicata extract 4-8% and again mix for 20-30 minutes.
7. At last mixed Glycyrrhiza Glabera with optimized concentration in above blend and mixed it for 15-20 min.
8. Viscosity adjusted with Natural gum of Phytoconstituents blend.
For the purpose of this invention the Ayurvedic plants constituents are selected from the following group:
Table 1. Ayurvedic plants constituents
Botanical name of Plant Therapeutic Properties Concentration (%)
Trachyspermum Ammi extract It has an anti-inflammatory antibacterial and stimulating expectorant action. 15-20
Glycyrrhiza Glabera extract It has an anti-inflammatory, demulcent and expectorant action. 15-20
Ocimum Sanctum extract It has an Anti-inflammatory, spasmolytic action and anti- bacterial action. 8-16
Piper longum extract It has an Expectorant, bronchodilator action. 6-10
Iris Germanica extract It has an Expectorant, spasmolytic, bronchodilator action. 4.5-9
Zingiber Officinale extract It has an Antipyretic action, 4-9
Solanum Nigrum extract It has an Anti-inflammatory, expectorant and antitussive action. 3.5-9
Piper betle extract It has an Anti-asthmatic and antibacterial action. 3-6
Piper nirgum extract It has an Antibacterial action. 3-6
Syzygium aromaticum ext It has an analgesic, anti-inflammatory, and anti-bacterial action. 2-6
Cinnamomum verum extract It has an Anti-inflammatory, Anti-Viral and antihistaminic action. 2-6
Curcuma Longa extract It has an Anti-inflammatory, Anti-Viral, and Anti-Sars-CO2 activity 1-4
Adhatoda vasaca ext It has an antitubercular action. 1-4

Examples and Evaluation parameters

a) Preparation of polyherbal composition:
Preparation of Herbal mixture
Adding raw extract of Trachyspermum Ammi extract, Glycyrrhiza Glabera extract, Ocimum Sanctum extract, Piper longum extract, Iris Germanica extract, Zingiber Officinale extract, Solanum Nigrum extract, Piper betle extract, Piper nirgum extract, Syzygium aromaticum extract, Cinnamomum verum extract, Curcuma Longa extract, Adhatoda vasaca extract in a beaker and mixing them well and converting the same into syrup. Dry all blend of Phytoconstituents at 40-55°C in tray dryer or fluidized bed dryer for 30-60 min. Pulverized it in sieve number 80-100. Check flowability of individual as per free flow compliance and mixed all in synergy form. Continue mixing of all improvised granules for 30-45 min and then add natural blend of Mentha Spicata extract 4-8% and again mix for 20-30 minutes. At last mixed Glycyrrhiza Glabera with optimized concentration in above blend and mixed it for 15-20 min. Viscosity adjusted with Natural gum of Phytoconstituents blend. The procedure is depicted in Table 1 below.
Table 2: polyherbal blend of sugar free dry syrup composition
Ingredients Concentration (%)
F1 F2 F3
Trachyspermum Ammi extract 15 17 20
Glycyrrhiza Glabera ext
16 18 19
Ocimum Sanctum extract 9 12 15
Piper longum extract 6 8 9
Iris Germanica extract 5 6 9
Zingiber Officinale extract 4 7 8
Solanum Nigrum extract 6 7 9
Piper betle extract 3 5 6
Piper nirgum extract 3 4 5
Syzygium aromaticum ext 2 5 6
Curcuma Longa extract 1 3 5
Adhatoda vasaca ext 2 3 4
fluidized bed dryer time - 30-60 min, Pulverize # 80-100 mesh

b) Evaluation of the polyherbal sugar free dry syrup composition
Colour
5 ml of final syrup is taken in a watch glasses and placed under light, and colour is observed by naked eye.
Odour
2 ml of final syrup is smelled individually and then the odour can be detected.
Taste
A pinch of final syrup is placed on the taste bud of tongue to identify the taste.
Determination of pH
Take 5 ml of final syrup in the volumetric flask and make the volume up to 50ml with purified water. The pH can be determined by using digital pH meter.
Determination of viscosity
Viscosity of herbal syrup can be determined by using an Ostwald viscometer. Ostwald viscometer is thoroughly cleaned with chromic acid or acetone. Viscometer should be placed in a vertical position in a suitable stand. Fill the water up to the mark in dried viscometer. Now note the time required for water to flow from mark A to mark Repeat the process for 3 times, to obtain accurate reading. Now is the viscometer and fill it with herbal syrup, and then note the time required for syrup to flow from mark A to mark B.
Determination of density
The density of syrup can be determined by using a pyncometer. Clean the pyncometer (specific gravity bottle) with chromic acid and nitric acid, and rinse with purified water. Note the weight of empty dry bottle (w1). Fill the pyncometer with 10 ml of water and weigh it (w2). Finally note the weight of bottle with 10 ml of syrup (w3).
Table 3: Evaluation parameter polyherbal blend of sugar free dry syrup composition
SR. No Evaluation Parameters Syrup formulation
1 Colour Reddish Brown
2 Odour Aromatic
3 Taste Lightly bitter
4 pH 6.2
5 Viscosity 1.05
6 Density 1.01

,CLAIMS:1. A polyherbal blend of sugar free dry syrup composition comprising of Trachyspermum Ammi extract, Glycyrrhiza Glabera extract, Ocimum Sanctum extract, Piper longum extract, Iris Germanica extract, Zingiber Officinale extract, Solanum Nigrum extract, Piper betle extract, Piper nirgum extract, Syzygium aromaticum extract, Cinnamomum verum extract, Curcuma Longa extract, Adhatoda vasaca extract to form sugar free dry syrup.
2. The polyherbal blend of sugar free dry syrup composition as claimed in claim 1, wherein the polyherbal composition which is non-alcoholic, non-sedating and non-freezing, high soluble, non-palatable, excipient less, preservative free with no artificial flavor dry syrup for antiviral activity & immunomodulator activity.
3. A method of preparation of polyherbal blend of sugar free dry syrup composition comprises of;
a. Synergy form of Curcumin mixed with Black piper, Lavang and Saponin blend of Liquorice for Anti-inflammatory effect by improve its poor characteristics.
b. Synergy form of Ajwain, Ginger, Cinnamon mixed for synergy Broncho dilation and Antihistaminic effect.
c. Synergy form of Betel leaf, Kakamachi and Lindipiper mixed for cough, cold and expectorant.
d. Synergy blend of Puskarmool, Tulsi and Vasaka mixed for its Antiviral, Anti-bacterial activity.
e. Dry all blend of Phytoconstituents at 40-55 0C in tray dryer or fluidized bed dryer for 30-60 min.
f. Pulverized it in sieve number 80-100.
g. Check flowability of individual as per free flow compliance and mixed all in synergy form.
h. Continue mixing of all improvised granules for 30-45 min and then add natural blend of Mentha Spicata extract 4-8% and again mix for 20-30 minutes.
i. At last mixed Glycyrrhiza Glabera with optimized concentration in above blend and mixed it for 15-20 min.
j. Viscosity adjusted with Natural gum of Phytoconstituents blend.
4. The polyherbal composition as claimed in claim 1, wherein the said polyherbal composition in the form of sugar free dry syrup can be used for antiviral activity & immunomodulator activity.