Title of Invention

A STABLE NON-ALCOHOLIC FORMULATION FOR TREATMENT OF RESPIRATORY DISORDER

Abstract

This invention describes a novel, stable formulation for the treatment of respiratory disorders such as cough. The formulation base/solvent herein is natural extract like date syrup and/ or honey and/or any other natural extract, which is also a replacement of alcohol as a solvent, commonly used in formulations prepared for the treatment of respiratory diseases. The solute could be any Expectorant and Mucolytic agent.

Full Text

This invention relates to A Novel Stable Formulation For Treatment Of Respiratory Disorder. FIELD OF INENTION: The invention particularly relates to the field of formulations particularly, for treating respiratory congestion due to cough. The invention more particularly relates to a stable formulation using aqueous extract as a substitute/alternative to generally employed alcohol base for treating respiratory congestion due to cough. Still more particularly the invention relates to using date syrup (aqueous extract of date) or honey as a base for conventional expectorant, mucolytics , narcotic cough suppressants and non-narcotic cough suppressants as a replacement for alcohol. Further, the formulation does not include any other ingredients and achieve the stability over 2 years. BACKGROUND OF THE INVENTION: Many drugs used for treating respiratory disorders are administered for nasal congestion. These formulations could be either Expectorant, Mucolytics , Narcotic cough suppressants and Non Narcotic cough suppressants. The commonly used expectorants are Ammonium chloride, Benzoin compounds, Guiphenesin Ipecacuanha, Menthol, Peppermint. The commonly used mucolytics are exemplified by Acetylcysteine, Carbocysteine, while generally used Narcotic cough suppressants are Codeine and Dextromethorphan and the Non Narcotic cough suppressants are Chlorpheniramine, Carbinoxamine, Iphenhydramine, Pheniramine, Promethazine and Tripolidine. Most of these formulations are based on alcohol as a solvent. These drugs act by various mechanisms as a therapeutic for nasal and chest congestion. Though formulations containing these drugs are very effective, the main drawback is the usage of alcohol as a solvent. Thus, the main solvent used in these formulations, which could either be single, or in combination is alcohol. The alcoholic base has its advantages as well as disadvantages. The main advantage is being sedative, it helps in rest and comfort to the patients. Whereas the main disadvantage associated with using alcohol, as a solvent is that it causes dizziness, which in turn occasionally likely to result in accidents leading to loss of human life. The other main drawback is development of addiction. The statistics shows that the continued use of alcohol base expectorants results in habituated drug addiction that requires special treatment to get rid of the addiction thus developed. Another main drawback is religious reasons. Many religions and sections prohibit the usage of alcohol. Hence these issues have led to the identification of an alternative to alcohol base. The alcohol free formulations available for treating respiratory congestion due to cough are invariably using number of other ingredients. Thus these formulations are not intended to replace alcohol that is used as base for the conventional solutes such as Expectorant, Mucolytics, Narcotic cough suppressants and Non Narcotic cough suppressants. The formulations known to the inventors are mainly ayurvedic or homeopathic and thus are not proven/evidenced for its efficacy and safety. In view of this there is an imperative need for developing a formulation that is safe, efficient as well as stable while avoiding at least partially if not eliminating the problems totally arising from the alcohol based formulations for treating respiratory congestion due to cough. Moreover, it is worthwhile to mention here that since active ingredient being used is the conventional well evidenced expectorant, mucolytics, narcotic cough suppressant and non narcotic cough suppressant, the replacement of alcohol, which is employed as a base by syrups obtained from natural sources such as botanicals or honey would not require any further evidence for safety. The inventors after prolong research have concluded that syrups obtained from natural sources particularly date syrup proves to be better substitute for alcohol for preparing the formulations of these drugs as herein before disclosed, for treating respiratory disorders particularly congestion due to cough. The date syrup may be substituted by honey or other, extract such as grape or beetroot extract. Date fruits, its syrup and honey have been widely used world wide and volumes of literature is available on its nutritional values and its benefits to mankind and till date no report on its side effects has ever been reported. The date syrup is prepared from date fruits; fruit are pressed, and the juice is concentrated and filtered. Date syrup is used as a sweetener as well as base for the active anti-coughing ingredient. Further, there are several other compounds in dates known to have medicinal value: fiber for a digestive aid, serotonin, which affects mood, emotion, sleep, and appetite, anthocyanins that act against cancer and as antioxidants, and estrones, which act as estrogenic hormones in mammals (1-4). Dates have high tannin content and are used medicinally as a detersive and astringent in intestinal troubles. Hence these formulations in addition to treating disorders of airways also provide nutritional support and supplement pharmaceutical remedies to the patients. SUMMARY OF THE INVENTION: The main object of the present invention is to provide a novel formulation for treatment of respiratory disorder. The other object is to provide a formulation that eliminates using alcohol as a base thereby obviating the drawbacks associated with alcohol as one of the ingredients. Another object is to provide a formulation wherein syrups obtained from natural sources exemplified but not restricting to date syrup and or honey as substitute the alcohol. Further, the basic material for syrup is easily available and proven to be eco- friendly. Yet other object is to provide formulation using date syrup as a replacement for alcohol. In the present invention, Date syrup and honey are preferably used as a base, and solute being conventional 'Expectorant' and or 'Mucolytic agents' as herein before described. These anti-coughing agents are formulated in date syrup and honey at the same concentration present in approved formulations, which provide relief from respiratory ailments. Various pharmacopoeial and non-pharmacopoeial tests were performed to establish the stability of the drugs. Data revealed that the solute agents were stable during the entire period of study thus confirming that date syrup and honey as a novel solvent for preparing formulations proves to be safe effective and efficient for respiratory ailments. Thus the scope of the present invention is not just limited to date syrup and honey as solvent but also to other syrups obtained from natural sources, which can be alternative to alcohol base for respiratory disorders. These syrups can be used individually/in isolation or in combination to provide better stability and nutritional support. However, date syrup and honey, based on it's physico-chemical, microbiological and other sensory tests were found to be the ideal base. Data on stability of various solutes as per ICH guidelines clearly indicate that date syrup and honey are an ideal base and also an appropriate replacement for alcohol base. BRIEF DESCRIPTION OF FIGURES: Figure 1: Real Time Stability Study of Salbutamol Sulphate HC1 in Date Syrup Figure 2: Real Time Stability Studies for Phenyl Propalamine HC1 in Date Syrup Figure 3: Real Time Stability Studies for Chloropheniramine HC1 Figure 4: Real Time Stability Studies of Guaiphenesin in Date Syrup Figure 5: Real Time Stability Studies of Salbutamol sulphate, PPM, CPM, Guaiphenesin in Date Syrup Figure 6. Accelerated Stability Studies of Salbutamol sulphate, PPM, CPM, Guaiphenesin in Date Syrup STATEMENT OF INVENTION: Accordingly the present invention provides a novel stable formulation for treatment of respiratory disorder comprising; (i) conventional anti-coughing agent as a solute, in an amount effective to administer to the subject that needs treatment of respiratory disorder and (ii) syrups obtained from natural sources as a base. The conventional anti-coughing agent used may be expectorant, mucolytics , narcotic cough suppressants and non- narcotic cough suppressants, any antibiotic, herbal drug, ayurvedic drug, homeopathic drug and /or any other defined pharmaceutical agent used as anti-cough agent. The expectorants used may be such as Ammonium chloride, Benzoin compounds, Guiphenesin Ipecacuanha, Menthol, Peppermint. The commonly used mucolytics used may be exemplified by Acetylcysteine, Carbocysteine. The generally used Narcotic cough suppressants used may be such as Codeine and Dextromethorphan. The Non Narcotic cough suppressants used may such as Chlorpheniramine, carbinoxamine, iphenhydramine, pheniramine, promethazine and tripolidine. Syrups obtained from natural sources as a base may be selected from date syrup or honey or any natural extract having reducing sugars 10-85%, glucose 10-45%, Further, the said base may have viscosity 1000-3500 cP and pH 3 - 6.5, which can retain the physiological function of base particularly date syrup or honey. DETAILED DESCRIPTION THE INVENTION: As required, detailed embodiments of the present invention are disclosed herein; however, it is to be understood that the disclosed embodiments are merely exemplary of the invention, which can be embodied in various forms. Therefore, specific structural and functional details disclosed herein are not to be interpreted as limiting, but merely as a basis for the claims and as a representative basis for teaching one skilled in the art to variously employ the present invention in virtually any appropriately detailed structure. Further, the terms and phrases used herein are not intended to be limiting but rather to provide an understandable description of the invention. The main objective of the invention is the usage of date syrup as a base for agents used as anti-coughing agents. Providing alternatives to alcohol base in preparation of anti-coughing agents is the main objective of the present invention. Date syrup and honey, based on it's physico-chemical, microbiological and other sensory tests were found to be ideal base. Data on stability of various solutes as per ICH guidelines clearly indicate that Date syrup and/or honey are an ideal solvent and also an appropriate replacement for alcohol base. Standard specifications for date syrup are as follow: Typical Composition of honey: Average Range Standard Deviation Fructose/Glucose Ratio 1.23 0.76-1.86 0.126 Fructose, % 38.38 30.91-44.26 1.77 Glucose, % 30.31 22.89-40.75 3.04 Minerals (Ash), % 0.169 0.020-1.028 0.15 Moisture, % 17.2 13.4-22.9 1.46 Reducing Sugars, % 76.75 61.39-83.72 2.76 Sucrose, % 1.31 0.25-7.57 0.87 pH 3.91 3.42-6.10 Total Acidity, meq/kg. 29.12 8.68-59.49 10.33 True Protein, mg/lOOg. 168.6 57.7-567 70.9 As a case study we have formulated date syrup as well as honey as a base for mucolytes, expectorants, narcotic and non narcotic cough suppressants such as Ammonium chloride, Salbutamol sulphate, Pseudophedrine hydrochloride, Chloropheniramine malete (CPM), Bromhexine hydrochloride, Guaiphenesin and Phenyl propalamine hydrochloride (PPM). EXAMPLES The following examples are included solely to aid in a more complete understanding of the invention described and claimed herein. The examples do not limit the scope of the claimed invention in any fashion. However, one of ordinary skill in the art appreciates that various modifications and changes can be made without departing from the scope of the present invention as set forth in the claims below. Accordingly, the specification and figures are to be regarded in an illustrative rather than a restrictive sense, and all such modifications are intended to be included within the scope of present invention. The benefits, advantages, solutions to problems, and any element(s) that may cause any benefit, advantage, or solution to occur or become more pronounced are not to be construed as a critical, required, or essential features or elements of any or all the claims. The invention is defined solely by the appended claims including any amendments made during the dependency of this application and all equivalents of those claims as issued. As per Indian Pharmacopoeia (IP), US Pharmacopoeia (USP) and ICH guidelines the real time stability studies, accelerated stability studies, temperature- humidity (T&H) studies have been done using date syrup as a solvent and individual mucolytes or expectorant or non narcotic component as solute as well as all in combination to make a stable and pharmaceutically acceptable formulation for the treatment of respiratory disorder or nasal congestion. Date syrup or honey as a base and Salbutamol sulphate, Pseudophedrine hydrochloride, Chloropheniramine malete and Guaiphenesin, all in combination as well as individually as a solute was tested for real time stability studies, accelerated stability studies and T&H studies as per the standard protocol. All the formulations were found to be stable at ambient conditions for two years. Example 1 Salbutamol sulphate hydrochloride (IP grade), 40mg was dissolved in 100 ml of date syrup or honey and assayed for stability studies at 25°C and accelerated stability studies at various temperatures and humidity such as 25°C/60%humidity, 30°C/65%humidity, and 40°C/75%humidity as per the Indian pharmacopoeia and ICH guidelines. Results are depicted in figure 1. The data clearly indicates that there is no significant drop in the content of Salbutamol sulphate hydrochloride and its formulation in date syrup/honey is stable for two years at ambient conditions. Example 2 Phenyl propalamine hydrochloride (PPM) IP grade, 250mg was dissolved in 100 ml of date syrup or honey and assayed for stability studies at 25°C and accelerated stability studies at various temperatures and humidity such as 25°C/60%humidity, 30°C/65%humidity, and 40°C/75%humidity as per the Indian pharmacopoeia and ICH guidelines. Results are depicted in figure 2. The data clearly indicates that there is no significant drop in the content of PPM and its formulation in date syrup/honey is stable for two years at ambient conditions. Example 3 Chloropheniramine malete (CPM) IP grade, 40mg was dissolved in 100 ml of date syrup or honey and assayed for stability studies at 25°C and accelerated stability studies at various temperatures and humidity such as 25°C/60%humidity, 30°C/65%humidity, and 40°C/75%humidity as per the Indian pharmacopoeia and ICH guidelines. Results are depicted in figure 3. The data clearly indicates that there is no significant drop in the content of CPM and its formulation in date syrup/honey is stable for two years at ambient conditions. Example 4 Guaiphenesin IP grade, Igm was dissolved in 100 ml of date syrup or honey and assayed for stability studies at 25°C and accelerated stability studies at various temperatures and humidity such as 25°C/60%humidity, 30°C/65%humidity, and 40°C/75%humidity as per the Indian pharmacopoeia and ICH guidelines. Results are depicted in figure 4. The data clearly indicates that there is no significant drop in the content of Guaiphenesin and its formulation in date syrup/honey is stable for two years at ambient conditions. Example 5 Salbutamol sulphate (0.4%), Pseudophedrine hydrochloride (0.25%), Chloropheniramine malete (0.4%) and Guaiphenesin (1%) IP grade were dissolved in 100 ml of date syrup or honey and assayed for stability studies at 25°C and accelerated stability studies at various temperatures and humidity such as 25°C/60%humidity, 30°C/65%humidity, and 40°C/75%humidity as per the Indian pharmacopoeia and ICH guidelines. Results are depicted in figure 5 and figure 6. The data clearly indicates that there is no significant drop in the content of Salbutamol sulphate HC15 PPM, CPM and Guaiphenesin and its formulation in date syrup/honey are stable for two years at ambient conditions. ADVANTAGES: (i) The formulation is equally stable (over 2 years) and efficient as compared with alcohol-based formulations, (ii) The formulation is safe, (iii) The formulation is devoid of any side effects, (iv) The formulation can also acts as a nutrient supplement. WE CLAIM: 1. A novel stable formulation for treatment of respiratory disorder comprising; (i) conventional anti-coughing agent as a solute, in an amount effective to administer to the subject that needs treatment of respiratory disorder and (ii) syrups obtained from natural sources as a base. 2. A formulation as claimed in claim 1 wherein the conventional anti-coughing agent used is expectorant, mucolytics, narcotic cough suppressants and non-narcotic cough suppressants, any antibiotic, herbal drug, ayurvedic drug, homeopathic drug and /or any other defined pharmaceutical agent used as anti-cough agent. 3. A formulation as claimed in claim 1 & 2 wherein the expectorants used is Ammonium chloride, Benzoin compounds, Guiphenesin Ipecacuanha, Menthol, Peppermint. 4. A formulation as claimed in claim 1 & 2 wherein the mucolytics used is exemplified by Acetylcysteine, Carbocysteine, and narcotic cough suppressants used is Codeine and Dextromethorphan. 5. A formulation as claimed in claim 1 & 2 wherein the Non Narcotic cough suppressants used is chloropheniramine, carbinoxamine, iphenhydramine, pheniramine, promethazine and tripolidine. 6. A formulation as claimed in claim 1 wherein syrups obtained from natural sources as a base is selected from date syrup or honey or any natural extract having reducing sugars 10-85%, glucose 10-45%. Further, the said base may have viscosity 1000-3500 cP and pH 3 - 6.5. 7. A novel stable formulation for treatment of respiratory disorder substantially as herein described.

Documents:

1642-CHE-2005 CORRESPONDENCE OTHERS 25-06-2010.pdf

1642-che-2005 correspondence others 18-03-2011.pdf

1642-che-2005 correspondence others 25-07-2011.pdf

1642-CHE-2005 CORRESPONDENCE OTHERS 27-10-2011.pdf

1642-che-2005 form-1 25-07-2011.pdf

1642-che-2005 form-13 18-03-2011.pdf

1642-CHE-2005 FORM-2 25-07-2011.pdf

1642-che-2005 form-3 25-07-2011.pdf

1642-che-2005 form-5 25-07-2011.pdf

1642-CHE-2005 AMANDED CLAIMS 05-03-2010.pdf

1642-CHE-2005 AMANDED PAGES OF SPECIFICATION 05-03-2010.pdf

1642-che-2005 amanded pages of specification 14-05-2010.pdf

1642-CHE-2005 CORRESPONDENCE OTHERS 01-12-2010.pdf

1642-CHE-2005 CORRESPONDENCE OTHERS 05-03-2010.pdf

1642-CHE-2005 CORRESPONDENCE OTHERS 16-04-2012.pdf

1642-che-2005 form-13 14-05-2010.pdf

1642-CHE-2005 FORM-13 16-04-2012.pdf

1642-CHE-2005 POWER OF ATTORNEY 16-04-2012.pdf

1642-che-2005-abstract.pdf

1642-che-2005-claims.pdf

1642-che-2005-correspondnece-others.pdf

1642-che-2005-description(complete).pdf

1642-che-2005-description(provisional).pdf

1642-che-2005-drawings.pdf

1642-che-2005-form 1.pdf

1642-che-2005-form 18.pdf

1642-che-2005-form 3.pdf

1642-che-2005-form 5.pdf