CA2017923A1 - Heated oral antitussive compositions - Google Patents
Heated oral antitussive compositionsInfo
- Publication number
- CA2017923A1 CA2017923A1 CA 2017923 CA2017923A CA2017923A1 CA 2017923 A1 CA2017923 A1 CA 2017923A1 CA 2017923 CA2017923 CA 2017923 CA 2017923 A CA2017923 A CA 2017923A CA 2017923 A1 CA2017923 A1 CA 2017923A1
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- CA
- Canada
- Prior art keywords
- pharmaceutical composition
- oral
- composition according
- treatment
- oral pharmaceutical
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Abandoned
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Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0087—Galenical forms not covered by A61K9/02 - A61K9/7023
- A61K9/0095—Drinks; Beverages; Syrups; Compositions for reconstitution thereof, e.g. powders or tablets to be dispersed in a glass of water; Veterinary drenches
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/045—Hydroxy compounds, e.g. alcohols; Salts thereof, e.g. alcoholates
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
Abstract
ABSTRACT OF THE DISCLOSURE
Disclosed are oral pharmaceutical compositions for the treatment of cough comprising: (a) from about 0.01% to about 0.25% of a vola-tile essential oil component having a vapor pressure of from about 0.05mm to about 15.0mm at 60-C; and (b) from about 50% to about 99% of a pharmaceutically acceptable oral carrier wherein said pharmaceu-tically acceptable carrier has a viscosity of from about 150 cps to about 800 cps and wherein said pharmaceutical composition has a temperature of from about 35°C to about 70°C. Also provided aremethods for the treatment of cough in humans or animals which com-prises orally administering to said human or animal a safe and effec-tive amount of these heated pharmaceutical compositions.
Disclosed are oral pharmaceutical compositions for the treatment of cough comprising: (a) from about 0.01% to about 0.25% of a vola-tile essential oil component having a vapor pressure of from about 0.05mm to about 15.0mm at 60-C; and (b) from about 50% to about 99% of a pharmaceutically acceptable oral carrier wherein said pharmaceu-tically acceptable carrier has a viscosity of from about 150 cps to about 800 cps and wherein said pharmaceutical composition has a temperature of from about 35°C to about 70°C. Also provided aremethods for the treatment of cough in humans or animals which com-prises orally administering to said human or animal a safe and effec-tive amount of these heated pharmaceutical compositions.
Description
3qli Zi:P17923 HEATED ORAL ANTlTU$SIVE COMPOS;TIONS
Gordon F. Brunner David A. Nichols TECHNICAL FIELD
The present invention relates to heated antitussive oral pharma-ceutical compositions containing a volatile essential oil component which has a vapor pressure of from about 0.05mm to about 15.0mm at 60C.
BACKGROUND OF THE INVENTION
The cough reflex is an important mechanism whereby secretions from the lungs and airways are removed. Generally, such secretions are removed by the mucociliary escalator. However, when this mecha-nism is defective, or becomes overwhelmed by, for example, excessive secretions, cough then becomes a principal means of secretion removal.
The cough reflex is initiated by stimulation of mechanical and irritant receptors and is controlled by afferent pathways within the vagus tX), glossopharyngeal (IX), and superior laryngeal nerves to the cough center in the brainstem. Cough can be caused by, for example, foreign bodies, dust, mucus, debris, gases and smoke in the lower respiratory tract. Irritation of various sensory nerves in the nose, sinuses, pharynx, ears, stomach, pericardium or diaphragm can also produce coughing. In many of these conditions, chronic or paroxysmal cough, however, can be exhausting and debilitating, particularly when it interferes with sleep.
Oral cough preparations, such as tablets, lozenges, syrups, solutions, suspensions and the like, containing an effective anti-tussive agent have long been used for the symptomatic relief of coughs. The most popular of such preparations contain either dextro-methorphan (or its hydrobromide salt) or codeine (or its sulfate salt) as the active antitussive agent. These remedies, among many others, are fully described in Drua Evaluations, 6th Ed., Chapter 21 (The American Medical Association, 1986).
Mixtures of honey and lemon juice have been disclosed as useful in treating cough. It has also been disclosed that hot water may also provide some relief from cough. Aromatics have also been used as a flavoring agent in cold and flu remedies. Many of these treatments are described in Medical Surqical Nursinq, 6th Ed. (The C.V. Mosby Company, 1975), pp. 553-555. However, while such remedies may soothe z 2i~17923 or warm the throat, they do not provlde any significant antitussive or decongestant actlon.
It has now been discovered that oral antitussive pharmaceutical compositions having a temperature of from about 35'C to about 70~C and which contain a volatile essential oil component having a vapor pres-sure of from about 0.05mm to about 15.0mm at 60'C along Wi.n a pharma-ceutically acceptable oral carrier having a viscosity of from about 150 cps to about 800 cps (at 25-C) provide improved antitussive and decongestant efficacy and/or improved relief as seen by the product user.
It is therefore an object of the present inventian to provide heated oral pharmaceutical compositions containing certain volatile essential oils which are highly efficacious in the treatment of cough.
It is still a further object of the present invention to provide a method of using these same pharmaceutical compositions in the treat-ment of cough in humans or animals.
SUMMARY OF THE INVENTION
The present invention relates to an oral pharmaceutical composi-tion for the treatment of cough comprising: (a) from about 0.01% to about 0.25% of a volatile essential oil component having a vapor pressure of from about 0.05mm to about l5.0mm at 60-C; and (b) from about 50% to about 99r. of a pharmaceutically acceptable oral carrier having a viscosity of from about 150 cps to about 800 cps, wherein said pharmaceutical composition has a temperature of from about 35-C
to about 70-C.
Preferably the volatile essential oil component is selected from the group consisting of menthol, eucalyptus oil, eugenol, camphor, thymol, anethole, eucalyptol, cineole, peppermint oil, cuminal, and citral and mixtures thereof.
Also provided are methods for the treatment of cough in humans or ; ; animals which comprise orally administering to said human or animal a safe and effective amount of these heated pharmaceutical compositions.
All percentages and ratios used herein are by weight unless otherwise indicated. All vapor pressures used herein are in milli-meters of mercury and all viscosities are in centipoises at 25-C.
DETAILED DESCRIPTION Of THE DEVELOPMENT
More specifically, the present invention provides oral antitus-sive pharmaceutical compositions and methods for the treatment of cough in humans or animals afflicted with the same. The compositions -3 2'J179Z3 of the present invention comprise: (a) from about 0.01% to about 0.2SY., preferably from about 0.02% to about 0.2% and most preferably from about 0.05% to about 0.15% of a volatlle essential oll component having a vapor pressure of from about O.OSmm to about 15.amm, prefera-S bly from about n.5mm to about 7.0mm and most preferably from aboutO.Smm to about 2.0mm at 60'C; and (b) from about 50% to about 99%, preferably from about 70% to about 99% of a pharmaceutically accept-able oral carrier having a viscosity of from about 150 cps to about 800 cps, preferably from about 150 cps to about 700 cps and most preferably from about lSO cps to about 600 cps and wherein said pharmaceutical composition has a temperature of from about 35'C to about 70 C, preferably from about 40 C to about 70 C, more preferably from about 50-C to about 65-C and most preferably from about 55-C to about 60-C.
Preferably, the volatile essential oil component is selected from the group consisting of menthol, eucalyptus oil, eugenol, camphor, thymol, anethole, eucalyptol, cineole, peppermint oil, cuminal, and citral and mixtures thereof.
By safe and effective amount is meant that amount which provides antitussive efficacy thereby alleviating or preventing cough at a reasonable benefit/risk ratio, as is attendant with any medical treatment. Obviously, the amount of the antitussive pharmaceutical composition which is administered will vary with such factors as the particular condition that is being treated, the severity of the condition that is being treated, the duration of the treatment, the physical condition of the patient, the nature of concurrent therapy (if any), the specific formulation and carrier employed, and the solubility and concentration of the antitussive used.
VOLATILE ESSENTIAL OI~S
The volatile essential oil components useful in the present invention have a vapor pressure at 60-C of from about O.OSmm to about 15.0mm.
Volatile essential oils are found in various plant organs and - tissues. They usually consist of the savory and odorous principles of the plants in which they exist. Additionally, they either pre-exist in the tissues or are produced by the reaction of certain constituents when the tissues are brought into contact with water. Volatile aromatics are also sometimes formed through destructive distillation, ~4~ 2~117923 as the oils of tar and amber These aromatics are sometimes referred to as pvrolea..
Certain volatile oils separate into a solid and liquid portion upon standing. The solid portion is generally referred to as stearop-S tene (e.g. thymol, camphor, and menthol), and the liquid portion iscalled eleoDtene. The useful volatile essential oil component is purified from these.
Volatile essential oil components which are useful in the compo-sitions of the present invention include organic acids, such as acetic, benzoic, cinnamic, phenylacetic, etc.; a7coho1s like benzyl alcohol, borneol, cinnamyl alcohol, citronellol, geraniol, linalool, menthol, phenylethyl alcohol, terpineol, etc.; a7dehydes such as anisaldehyde, cinnamaldehyde, benzaldehyde, citral, piperonal or heliotropin, salicylaldehyde, vanillin, etc,; ketones like carvone, camphor, thujone, pulegone, etc.; esters such as bornyl acetate, methyl salicylate, benzyl benzoate, geranyl acetate, linalyl acetate, etc.; pheno7s such as thymol, carvacrol, chavicol, etc.; pheno7 ethers like anethole, eugenol, safrol, etc.; others such as eucalyptus oil, eucalyptol, cuminal and peppermint oil and many other more complex compounds, such as coumarin, indole, etc. Many of these products are found in flower oils and are used in the production of synthetic perfumes. Mixtures of these volatile essential oils may also be used.
Preferably the volatile essential oil component is selected from the group consisting of menthol, eucalyptus oil, eugenol, camphor, thymol, anethole, eucalyptol, cineole, peppermint oil, cuminal, and citral and mixtures thereof.
It has been found that the compositions of the present invention containing these volatile essential oil components with these specific vapor pressures provide improved antitussive and decongestant efficacy and/or improved relief as seen by the product user.
The usual approximate vapor pressures (at 60C) for preferred volatile aromatic or essential oils are indicated in the following table:
zi~7923 APPROXIMATE VAPOR
COMPONENT PRESSURE (mm of Hq) Menthol 1 0 Eucalyptus Oil 10.0 Eugenol <1.0 Camphor >1.5 Thymol 1.0 Anethole 1 0 Eucalyptol 12.0 Peppermint 1.0 Cuminal 1.0 Citral 1.0 OPTIONAL COMPONENTS
Preferably the oral antitussive csmpositions of the present invention contain other known th~rapeutic agents typically used in cough/cold preparations described below. The compositions of the present invention typically contain from about O.OlYo to about 1.0% of such agents.
A particularly preferred optional therapeutic agent is an oral antitussive drug. As used herein, the term "oral antitussive drug"
means a drug that is taken by mouth and acts systemically to relieve cough (see Federal Register, Vol. 52, No. 155, 12 August 1987, page 30055)-Useful recognized oral antitussive drugs include, but are not limited to, for example, the non-narcotic types such as dextromethor-phan and its acid salts, preferably the hydrobromide, chlophedianol hydrochloride~ carbetapentane citrate, caramiphen edisylate, diphenhy-dramine and its hydrochloride salt, fominoben, and the like, and the narcotic type such as codeine and its sulfate or phosphate salts, noscapine hydrochloride, hydrocodone and its bitartrate salt, hydro-morphone hydrochloride, and the like. The usual adult dosages for such antitussives, which may also be utilized per dose in the subject compositions, are indicated in Table I.
~ABLE I 2~1~L7923 Usual Adult Oral Antitu$stve Orug Oose ~mq) Dextromethorphan HBr 10-30 Chlophedianol HCl 15-25 Carbetapentane citrate 15-30 Caramiphen edisylate 15-20 Noscapine HCl 15-30 Diphenhydramine HCl 15-25 Codeine sulfate 10-20 Hydrocodone bitartrate S-10 Hydromorphone HCl 2 Fominoben 80-160 Preferred oral antitussive agents are dextromethorphan, codeine lS and diphenhydramine and pharmaceutically acceptable salts thereof and mixtures thereof. Even more preferred are dextromethorphan and codeine, pharmaceutically acceptable salts thereof and mixtures thereof. Most preferred is dextromethorphan and its pharmaceutically acceptable salts.
As used herein, the term "oral decongestant drug" means a drug that is taken by mouth and acts systemically to relieve congestion (see Federal Register, Vol. SO, No. 10, lS January 1985, pp. 2220-2240). Preferred oral decongestant drugs include pseudoephedrine hydrochloride, phenylpropanolamine hydrochloride, phenylephrine hydro-chloride and ephedrine hydrochloride and mixtures thereof.
The volatile essential oil components are used along with a suitable liquid oral carrier. Liquid oral carriers useful in the present invention have a viscosity ranging from about lSO cps to about 800 cps, preferably from about lSO cps to about 700 cps and most preferably from about 150 to about 600. Various liquid oral dosage forms can be used, including syrups, suspensions and solutions.
These oral forms comprise a safe and effective amount, usually at least about 0.01% of the active component. Liquid oral dosage forms preferably contain from about O.OlY, to about 0.25%, more preferably from about 0.02% to about 0.2% and most preferably from about 0.05% to about 0.15% of the volatile essential oil component.
~7~ 2~17923 Liquid oral dosage forms lnclude aqueous and nonaqueous solu-tions, emulsions, suspensions, solutions and/or suspensions recons-tituted from non-effervescent granules, containing suitable solvents, preservatives, emulsifying agents, suspending agents, diluents, sweetening agents, coloring agents, and flavoring agents. Preferred carriers for oral administration include water, simple syrup, poly-ethylene glycol, alcohol, corn syrup, invert sugar, gelatin, propylene glycol, ethyl oleate, cottonseed oil and sesame oil and mixtures thereof. Specific examples of pharmaceutically acceptable carriers and excipients that may be used to formulate oral dosage forms, are described in U.S. Patent 3,903,297, Robert, issued September 2, 1975, incorporated by reference herein.
Since many of the optional oral antitussive drugs are generally used in the form of a water-soluble salt, they can be readily incor-I5 porated into conventional aqueous-based cough syrups and solution formulations. Water-insoluble or poorly soluble antitussives, gener-ally in base form, may also be incorporated into aqueous-based orally acceptable pharmaceutical carriers such as dispersions, suspensions, oil-in-water emulsions and the like by means of suitable dispersing, suspending or emulsifying agents, respectively, which are readily apparent to those skilled in the art of pharmaceutical formulations.
In preparing the pharmaceutical compositions of the present invention, the volatile essential oil components are incorporated into an aqueous-based orally acceptable pharmaceutical carrier consistent with conventional pharmaceutical practices. An "aqueous-based orally acceptable pharmaceutical carrier" is one wherein the entire or predominant solvent content is water. Typical carriers include simple aqueous solutions, syrups, dispersions and suspensions, and aqueous based emulsions such as the oil-in-water type. The most preferred carrier is a solution or suspension of the pharmaceutical composition in an aqueous vehicle containing a suitable suspending agent. Suit-able suspending agents include Avicel RlC-591 (a microcrystalline cellulose/sodium carboxymethyl cellulose mixture available from FMC), guar gum and the like. Such suspending agents are well known to those skilled in the art. While the amount of water in the compositions of this invention can vary over quite a wide range depending upon the total weight and volume of volatile essential oil component and other optional active and non-active ingredients, the total water content, -8- Z~17923 based on the weight of the final composition, will generally range from about 20 to about 75%, and, preferably, from about 20 to about 40%, by weight/volume.
Although water itself may make up much of the entire carrier, typical cough formulations preferably contain a co-solvent, for example, propylene glycol, glycerin, sorbitol solution and the like, to assist solubilization and incorporation of water-insoluble ingre-dient, flavoring oils and the like into the composition. In general, therefore, the compositions of this invention preferably contain from about 5 to about 25 volume/volume percent and, most preferably, from about 10 to about 20 volume/ volume percent, of the co-solvent.
If required, to provide and maintain the subject compositions at a pH of from about 2 to about 10 and preferably from about 4 to about 7, buffers consistent with conventional pharmaceutical practices are generally utilized such as, for example, sodium citrate buffer, sodium phosphate buffer, and the like. The compositions of this invention may optionally contain one or more other known therapeutic agents, particularly those commonly utilized in cough/cold preparations, such as, for example, an analgesic such as acetaminophen and ibuprofen; an expectorant or mucolytic such as glyceryl guaiacolate, guaiacolate, terpin hydrate, ammonium chloride, N-acetylcysteine and ambroxol; and an antihistamine such as chlorpheniramine maleate, doxylamine suc-cinate, brompheniramine maleate and diphenhydramine hydrochloride:
all of which are described in U.S. Patent 4,619,934 to Sunshine et al., issued October 28, 1986, which is incorporated by reference herein. Also useful are bronchodilators such as theophylline and albuterol.
The subject compositions are then heated to a temperature of from about 35-C to about 70-C, preferably from about 40-C to about 70-C, more preferably from about 50-C to about 65-C and most preferably from about 55-C to about 60-C. By ~heating" herein is meant radiant, conductive, or convective exposure to energy of a type which imparts thermal energy to the product being heated. Suitable methods of heating include conventional, infrared, convection and microwave heating. Most preferred is microwave heating.
Other optional ingredients well known to the pharmacist's art may also be included in amounts generally known for these ingredients, for example, natural or artificial sweeteners, flavoring agents, colorants -9- 2~.J179~3 and the like to provide a palatable and pleasant looking final pro-duct; antioxidants, ~or e~ample, butylated hydroxy an~sole or butylat-ed hydroxy toluene, and preservatives, for example, methyl or propyl paraben or sodium benzoate, to prolong and enhance shelf life.
METHOO OF TREATMENT
The present invention also encompasses methods of treating cough in humans or lower animals through administering, to the human or lower animal in need of such treatment, a safe and effective amount of a pharmaceutical composition comprising: (a) from about 0.01% to about 0.25%, preferably from about 0.02% to about 0.2% and most preferably from about 0.05% to about O.l5YO of a volatile essential oil component having a vapor pressure of from about 0.05mm tD about 15.0mm, preferably from about O.5mm to about 7.0mm and most preferably from about O.OSmm to about 2.0mm at 60-C; and (b) from about 50% to about 99%, preferably from about 70% to about 99% of a pharmaceuti-cally acceptable oral carrier having a viscosity of from about 150 cps to about 800 cps, preferably from about 150 cps to about 700 cps and most preferably from about 150 cps to about 600 cps, wherein said pharmaceutical composition has a temperature of from about 35~C to about 70C, preferably from about ~0C to about 70-C, more preferably from about 50-C to about 65-C and most preferably from about 55C to about 60-C.
The amount of the pharmaceutical composition administered depends upon the percent of active ingredients within its formula, which is a function of the amount of the volatile essential oil components required per dose, stability, release characteristics and other pharmaceutical parameters. Usually from about 150 mg/kg to about 3600 mg/kg per day, preferably from about 150 mg/kg to about 2000 mg/kg per day and most preferably from about 150 mg/kg per day to about 1000 mg/kg per day of the pharmaceutical composition is administered as described herein. This amount can be given in a single dose or, preferably, in multiple (two to six) doses repeatedly over the course of treatment. Generally, each individual dosage of the pharmaceutical compositions of the present invention range from about 100 mg/kg to about 600 mg/kg, preferably from about 75 mg/kg to about 300 mg/kg and most preferably from about 50 mg/kg to about 150 mg/kg. While dosages higher than the foregoing are effective to prevent cough, care must be taken, as with any drug, in some individuals to prevent adverse side effects.
- l- Z~17923 The compositions and methods described herein are used in an art recognized manner to provide antitUss~ve act~vity.
The following non-limlting e~amples illustrate embodiments of the subject invention wherein both essential and optional ingredients are combined. It is to be understood that these examples are for illus-trative purposes only and are not to be construed as limiting the scope of the invention thereto.
EXAMPLE I
A syrup for oral administration is prepared by combining the following ingredients:
Ingredient (wt %) Menthol (vapor pressure - lmm at 60'C) 0.1 Ethanol 10.0 Sucrose 45.0 Purified Water and Colorant q.s.
The above ingredients are combined to provide a solution (having a viscosity of about 100 cps) which is then heated to a temperature of about 60-C. 30 ml of this heated formulation are administered to an adult human in need of treatment, thereby reducing cough and conges-tion.
Substantially similar results are obtained when the mentholcomponent is replaced in whole or in part with acetic acid, benzoic acid, cinnamic acid, phenylacetic acid, benzyl alcohol, borneol, cinnamyl alcohol, citronellol, geraniol, linalool, phenylethyl al-cohol, terpineol, anisaldehyde, cinnamaldehyde, benzaldehyde, citral,piperonal, heliotrcpin, salicylaldehyde, vanillin, carvone, camphor, thujone, pulegone, bornyl acetate, methyl salicylate, benzyl benzoate, geranyl acetate, linalyl acetate, thymol, carvacrol, chavicol, ane-thole, eugenol, safrol, coumarin, indole, and mixtures thereof.
EXAMPLE II
A syrup for oral administration is prepared by combining the following ingredients:
Menthol 0.075%
Eucalyptus Oil 0.025%
Ethanol 5.0%
Propylene Glycol 10.0%
Sucrose 40.0%
Invert Syrup 30.0%
Water and Color q.s.
- 1 1 - 2~.-117923 The abo~e ingredients are combined to provlde a solution (having a viscosity of about 300 cps) which ls then heated to a temperature of about 60'C. 30 ml of this heated formulation are administered to an adult human in need of treatment, thereby reducing cough and conges-tion.
Substantially similar results are obtained when the propylene glycol component is replaced in whole or in part with water, simple syrup, polyethylene glycol, alcohol, corn syrup, invert sugar, gela-tin, ethyl oleate, cottonseed oil and sesame oil and mixtures thereof.
EXAMPEE II~
A syrup for oral administration is prepared by combining the following ingredients:
Inaredient WtX
Menthol a. 1%
Dextromethorphan HBr O.lX
Citric Acid 0.02~o Glycerin 10.0%
Invert Syrup (70%) 50.0%
Ethanol 5.0%
Purified Water and tolorant qs The citric acid is dissolved in the water and ethanol at room temperature. While stirring, the menthol, glycerin and dextromethor-phan HBr are added to this mixture and the color is added. The invert syrup is then added thereby producing a thick syrupy liquid (having a viscosity of about 200 cps). The resulting syrup is then heated to 60-C. 30 ml of this heated syrup is administered to an adult human in need of treatment, thereby reducing cough.
Substantially similar results are obtained when the dextro-methorphan is replaced in whole or in part with a therapeutically equivalent level of chlophedianol, carbetapentane, caramiphen, no-scapine, diphenhydramine, codeine, hydrocodone, hydromorphone, fomino-ben, their pharmaceutically-acceptable salts, and mixtures thereof.
EXAMPLE IV
A suspension for oral administration is prepared by combining the following ingredients:
-l2- Z~17923 Ingredient Amount Menthol 0.1%
Dextromethorphan HBr 0.1%
Pseudoephedrine hydrochloride 0.07%
S Microcrystalline cellulose and sodium carboxy methyl cellulose1.25%
Sucrose 45.0%
Glycerin 5-0%
Sorbitol solution (70%) 20.0%
Potassium sorbate 0.1%
Sodium saccharin 0.2%
Purified water and Colorant q.s.
The above ingredients are combined to produce a suspension (having a viscosity of about 350 cps), which is then heated to a temperature of 60-C. 30 ml of this heated formulation are administer-ed to an adult human in need of treatment, thereby reducing cough.
Substantially similar results are obtained when the dextromethor-phan is replaced in whole or in part with a therapeutically equivalent level of chlophedianol, carbetapentane, caramiphen, noscapine, diphen-hydramine, codeine, hydrocodone, hydromorphone, fominoben, theirpharmaceutically-acceptable salts, and mixtures thereof.
Substantially similar results are obtained when the pseudo-ephedrine hydrochloride is replaced in whole or in part with a thera-peutically equivalent level of phenylpropanolamine, phenylephrine, their pharmaceutically acceptable salts, and mixtures thereof.
WHAT IS CLAIMED IS:
Gordon F. Brunner David A. Nichols TECHNICAL FIELD
The present invention relates to heated antitussive oral pharma-ceutical compositions containing a volatile essential oil component which has a vapor pressure of from about 0.05mm to about 15.0mm at 60C.
BACKGROUND OF THE INVENTION
The cough reflex is an important mechanism whereby secretions from the lungs and airways are removed. Generally, such secretions are removed by the mucociliary escalator. However, when this mecha-nism is defective, or becomes overwhelmed by, for example, excessive secretions, cough then becomes a principal means of secretion removal.
The cough reflex is initiated by stimulation of mechanical and irritant receptors and is controlled by afferent pathways within the vagus tX), glossopharyngeal (IX), and superior laryngeal nerves to the cough center in the brainstem. Cough can be caused by, for example, foreign bodies, dust, mucus, debris, gases and smoke in the lower respiratory tract. Irritation of various sensory nerves in the nose, sinuses, pharynx, ears, stomach, pericardium or diaphragm can also produce coughing. In many of these conditions, chronic or paroxysmal cough, however, can be exhausting and debilitating, particularly when it interferes with sleep.
Oral cough preparations, such as tablets, lozenges, syrups, solutions, suspensions and the like, containing an effective anti-tussive agent have long been used for the symptomatic relief of coughs. The most popular of such preparations contain either dextro-methorphan (or its hydrobromide salt) or codeine (or its sulfate salt) as the active antitussive agent. These remedies, among many others, are fully described in Drua Evaluations, 6th Ed., Chapter 21 (The American Medical Association, 1986).
Mixtures of honey and lemon juice have been disclosed as useful in treating cough. It has also been disclosed that hot water may also provide some relief from cough. Aromatics have also been used as a flavoring agent in cold and flu remedies. Many of these treatments are described in Medical Surqical Nursinq, 6th Ed. (The C.V. Mosby Company, 1975), pp. 553-555. However, while such remedies may soothe z 2i~17923 or warm the throat, they do not provlde any significant antitussive or decongestant actlon.
It has now been discovered that oral antitussive pharmaceutical compositions having a temperature of from about 35'C to about 70~C and which contain a volatile essential oil component having a vapor pres-sure of from about 0.05mm to about 15.0mm at 60'C along Wi.n a pharma-ceutically acceptable oral carrier having a viscosity of from about 150 cps to about 800 cps (at 25-C) provide improved antitussive and decongestant efficacy and/or improved relief as seen by the product user.
It is therefore an object of the present inventian to provide heated oral pharmaceutical compositions containing certain volatile essential oils which are highly efficacious in the treatment of cough.
It is still a further object of the present invention to provide a method of using these same pharmaceutical compositions in the treat-ment of cough in humans or animals.
SUMMARY OF THE INVENTION
The present invention relates to an oral pharmaceutical composi-tion for the treatment of cough comprising: (a) from about 0.01% to about 0.25% of a volatile essential oil component having a vapor pressure of from about 0.05mm to about l5.0mm at 60-C; and (b) from about 50% to about 99r. of a pharmaceutically acceptable oral carrier having a viscosity of from about 150 cps to about 800 cps, wherein said pharmaceutical composition has a temperature of from about 35-C
to about 70-C.
Preferably the volatile essential oil component is selected from the group consisting of menthol, eucalyptus oil, eugenol, camphor, thymol, anethole, eucalyptol, cineole, peppermint oil, cuminal, and citral and mixtures thereof.
Also provided are methods for the treatment of cough in humans or ; ; animals which comprise orally administering to said human or animal a safe and effective amount of these heated pharmaceutical compositions.
All percentages and ratios used herein are by weight unless otherwise indicated. All vapor pressures used herein are in milli-meters of mercury and all viscosities are in centipoises at 25-C.
DETAILED DESCRIPTION Of THE DEVELOPMENT
More specifically, the present invention provides oral antitus-sive pharmaceutical compositions and methods for the treatment of cough in humans or animals afflicted with the same. The compositions -3 2'J179Z3 of the present invention comprise: (a) from about 0.01% to about 0.2SY., preferably from about 0.02% to about 0.2% and most preferably from about 0.05% to about 0.15% of a volatlle essential oll component having a vapor pressure of from about O.OSmm to about 15.amm, prefera-S bly from about n.5mm to about 7.0mm and most preferably from aboutO.Smm to about 2.0mm at 60'C; and (b) from about 50% to about 99%, preferably from about 70% to about 99% of a pharmaceutically accept-able oral carrier having a viscosity of from about 150 cps to about 800 cps, preferably from about 150 cps to about 700 cps and most preferably from about lSO cps to about 600 cps and wherein said pharmaceutical composition has a temperature of from about 35'C to about 70 C, preferably from about 40 C to about 70 C, more preferably from about 50-C to about 65-C and most preferably from about 55-C to about 60-C.
Preferably, the volatile essential oil component is selected from the group consisting of menthol, eucalyptus oil, eugenol, camphor, thymol, anethole, eucalyptol, cineole, peppermint oil, cuminal, and citral and mixtures thereof.
By safe and effective amount is meant that amount which provides antitussive efficacy thereby alleviating or preventing cough at a reasonable benefit/risk ratio, as is attendant with any medical treatment. Obviously, the amount of the antitussive pharmaceutical composition which is administered will vary with such factors as the particular condition that is being treated, the severity of the condition that is being treated, the duration of the treatment, the physical condition of the patient, the nature of concurrent therapy (if any), the specific formulation and carrier employed, and the solubility and concentration of the antitussive used.
VOLATILE ESSENTIAL OI~S
The volatile essential oil components useful in the present invention have a vapor pressure at 60-C of from about O.OSmm to about 15.0mm.
Volatile essential oils are found in various plant organs and - tissues. They usually consist of the savory and odorous principles of the plants in which they exist. Additionally, they either pre-exist in the tissues or are produced by the reaction of certain constituents when the tissues are brought into contact with water. Volatile aromatics are also sometimes formed through destructive distillation, ~4~ 2~117923 as the oils of tar and amber These aromatics are sometimes referred to as pvrolea..
Certain volatile oils separate into a solid and liquid portion upon standing. The solid portion is generally referred to as stearop-S tene (e.g. thymol, camphor, and menthol), and the liquid portion iscalled eleoDtene. The useful volatile essential oil component is purified from these.
Volatile essential oil components which are useful in the compo-sitions of the present invention include organic acids, such as acetic, benzoic, cinnamic, phenylacetic, etc.; a7coho1s like benzyl alcohol, borneol, cinnamyl alcohol, citronellol, geraniol, linalool, menthol, phenylethyl alcohol, terpineol, etc.; a7dehydes such as anisaldehyde, cinnamaldehyde, benzaldehyde, citral, piperonal or heliotropin, salicylaldehyde, vanillin, etc,; ketones like carvone, camphor, thujone, pulegone, etc.; esters such as bornyl acetate, methyl salicylate, benzyl benzoate, geranyl acetate, linalyl acetate, etc.; pheno7s such as thymol, carvacrol, chavicol, etc.; pheno7 ethers like anethole, eugenol, safrol, etc.; others such as eucalyptus oil, eucalyptol, cuminal and peppermint oil and many other more complex compounds, such as coumarin, indole, etc. Many of these products are found in flower oils and are used in the production of synthetic perfumes. Mixtures of these volatile essential oils may also be used.
Preferably the volatile essential oil component is selected from the group consisting of menthol, eucalyptus oil, eugenol, camphor, thymol, anethole, eucalyptol, cineole, peppermint oil, cuminal, and citral and mixtures thereof.
It has been found that the compositions of the present invention containing these volatile essential oil components with these specific vapor pressures provide improved antitussive and decongestant efficacy and/or improved relief as seen by the product user.
The usual approximate vapor pressures (at 60C) for preferred volatile aromatic or essential oils are indicated in the following table:
zi~7923 APPROXIMATE VAPOR
COMPONENT PRESSURE (mm of Hq) Menthol 1 0 Eucalyptus Oil 10.0 Eugenol <1.0 Camphor >1.5 Thymol 1.0 Anethole 1 0 Eucalyptol 12.0 Peppermint 1.0 Cuminal 1.0 Citral 1.0 OPTIONAL COMPONENTS
Preferably the oral antitussive csmpositions of the present invention contain other known th~rapeutic agents typically used in cough/cold preparations described below. The compositions of the present invention typically contain from about O.OlYo to about 1.0% of such agents.
A particularly preferred optional therapeutic agent is an oral antitussive drug. As used herein, the term "oral antitussive drug"
means a drug that is taken by mouth and acts systemically to relieve cough (see Federal Register, Vol. 52, No. 155, 12 August 1987, page 30055)-Useful recognized oral antitussive drugs include, but are not limited to, for example, the non-narcotic types such as dextromethor-phan and its acid salts, preferably the hydrobromide, chlophedianol hydrochloride~ carbetapentane citrate, caramiphen edisylate, diphenhy-dramine and its hydrochloride salt, fominoben, and the like, and the narcotic type such as codeine and its sulfate or phosphate salts, noscapine hydrochloride, hydrocodone and its bitartrate salt, hydro-morphone hydrochloride, and the like. The usual adult dosages for such antitussives, which may also be utilized per dose in the subject compositions, are indicated in Table I.
~ABLE I 2~1~L7923 Usual Adult Oral Antitu$stve Orug Oose ~mq) Dextromethorphan HBr 10-30 Chlophedianol HCl 15-25 Carbetapentane citrate 15-30 Caramiphen edisylate 15-20 Noscapine HCl 15-30 Diphenhydramine HCl 15-25 Codeine sulfate 10-20 Hydrocodone bitartrate S-10 Hydromorphone HCl 2 Fominoben 80-160 Preferred oral antitussive agents are dextromethorphan, codeine lS and diphenhydramine and pharmaceutically acceptable salts thereof and mixtures thereof. Even more preferred are dextromethorphan and codeine, pharmaceutically acceptable salts thereof and mixtures thereof. Most preferred is dextromethorphan and its pharmaceutically acceptable salts.
As used herein, the term "oral decongestant drug" means a drug that is taken by mouth and acts systemically to relieve congestion (see Federal Register, Vol. SO, No. 10, lS January 1985, pp. 2220-2240). Preferred oral decongestant drugs include pseudoephedrine hydrochloride, phenylpropanolamine hydrochloride, phenylephrine hydro-chloride and ephedrine hydrochloride and mixtures thereof.
The volatile essential oil components are used along with a suitable liquid oral carrier. Liquid oral carriers useful in the present invention have a viscosity ranging from about lSO cps to about 800 cps, preferably from about lSO cps to about 700 cps and most preferably from about 150 to about 600. Various liquid oral dosage forms can be used, including syrups, suspensions and solutions.
These oral forms comprise a safe and effective amount, usually at least about 0.01% of the active component. Liquid oral dosage forms preferably contain from about O.OlY, to about 0.25%, more preferably from about 0.02% to about 0.2% and most preferably from about 0.05% to about 0.15% of the volatile essential oil component.
~7~ 2~17923 Liquid oral dosage forms lnclude aqueous and nonaqueous solu-tions, emulsions, suspensions, solutions and/or suspensions recons-tituted from non-effervescent granules, containing suitable solvents, preservatives, emulsifying agents, suspending agents, diluents, sweetening agents, coloring agents, and flavoring agents. Preferred carriers for oral administration include water, simple syrup, poly-ethylene glycol, alcohol, corn syrup, invert sugar, gelatin, propylene glycol, ethyl oleate, cottonseed oil and sesame oil and mixtures thereof. Specific examples of pharmaceutically acceptable carriers and excipients that may be used to formulate oral dosage forms, are described in U.S. Patent 3,903,297, Robert, issued September 2, 1975, incorporated by reference herein.
Since many of the optional oral antitussive drugs are generally used in the form of a water-soluble salt, they can be readily incor-I5 porated into conventional aqueous-based cough syrups and solution formulations. Water-insoluble or poorly soluble antitussives, gener-ally in base form, may also be incorporated into aqueous-based orally acceptable pharmaceutical carriers such as dispersions, suspensions, oil-in-water emulsions and the like by means of suitable dispersing, suspending or emulsifying agents, respectively, which are readily apparent to those skilled in the art of pharmaceutical formulations.
In preparing the pharmaceutical compositions of the present invention, the volatile essential oil components are incorporated into an aqueous-based orally acceptable pharmaceutical carrier consistent with conventional pharmaceutical practices. An "aqueous-based orally acceptable pharmaceutical carrier" is one wherein the entire or predominant solvent content is water. Typical carriers include simple aqueous solutions, syrups, dispersions and suspensions, and aqueous based emulsions such as the oil-in-water type. The most preferred carrier is a solution or suspension of the pharmaceutical composition in an aqueous vehicle containing a suitable suspending agent. Suit-able suspending agents include Avicel RlC-591 (a microcrystalline cellulose/sodium carboxymethyl cellulose mixture available from FMC), guar gum and the like. Such suspending agents are well known to those skilled in the art. While the amount of water in the compositions of this invention can vary over quite a wide range depending upon the total weight and volume of volatile essential oil component and other optional active and non-active ingredients, the total water content, -8- Z~17923 based on the weight of the final composition, will generally range from about 20 to about 75%, and, preferably, from about 20 to about 40%, by weight/volume.
Although water itself may make up much of the entire carrier, typical cough formulations preferably contain a co-solvent, for example, propylene glycol, glycerin, sorbitol solution and the like, to assist solubilization and incorporation of water-insoluble ingre-dient, flavoring oils and the like into the composition. In general, therefore, the compositions of this invention preferably contain from about 5 to about 25 volume/volume percent and, most preferably, from about 10 to about 20 volume/ volume percent, of the co-solvent.
If required, to provide and maintain the subject compositions at a pH of from about 2 to about 10 and preferably from about 4 to about 7, buffers consistent with conventional pharmaceutical practices are generally utilized such as, for example, sodium citrate buffer, sodium phosphate buffer, and the like. The compositions of this invention may optionally contain one or more other known therapeutic agents, particularly those commonly utilized in cough/cold preparations, such as, for example, an analgesic such as acetaminophen and ibuprofen; an expectorant or mucolytic such as glyceryl guaiacolate, guaiacolate, terpin hydrate, ammonium chloride, N-acetylcysteine and ambroxol; and an antihistamine such as chlorpheniramine maleate, doxylamine suc-cinate, brompheniramine maleate and diphenhydramine hydrochloride:
all of which are described in U.S. Patent 4,619,934 to Sunshine et al., issued October 28, 1986, which is incorporated by reference herein. Also useful are bronchodilators such as theophylline and albuterol.
The subject compositions are then heated to a temperature of from about 35-C to about 70-C, preferably from about 40-C to about 70-C, more preferably from about 50-C to about 65-C and most preferably from about 55-C to about 60-C. By ~heating" herein is meant radiant, conductive, or convective exposure to energy of a type which imparts thermal energy to the product being heated. Suitable methods of heating include conventional, infrared, convection and microwave heating. Most preferred is microwave heating.
Other optional ingredients well known to the pharmacist's art may also be included in amounts generally known for these ingredients, for example, natural or artificial sweeteners, flavoring agents, colorants -9- 2~.J179~3 and the like to provide a palatable and pleasant looking final pro-duct; antioxidants, ~or e~ample, butylated hydroxy an~sole or butylat-ed hydroxy toluene, and preservatives, for example, methyl or propyl paraben or sodium benzoate, to prolong and enhance shelf life.
METHOO OF TREATMENT
The present invention also encompasses methods of treating cough in humans or lower animals through administering, to the human or lower animal in need of such treatment, a safe and effective amount of a pharmaceutical composition comprising: (a) from about 0.01% to about 0.25%, preferably from about 0.02% to about 0.2% and most preferably from about 0.05% to about O.l5YO of a volatile essential oil component having a vapor pressure of from about 0.05mm tD about 15.0mm, preferably from about O.5mm to about 7.0mm and most preferably from about O.OSmm to about 2.0mm at 60-C; and (b) from about 50% to about 99%, preferably from about 70% to about 99% of a pharmaceuti-cally acceptable oral carrier having a viscosity of from about 150 cps to about 800 cps, preferably from about 150 cps to about 700 cps and most preferably from about 150 cps to about 600 cps, wherein said pharmaceutical composition has a temperature of from about 35~C to about 70C, preferably from about ~0C to about 70-C, more preferably from about 50-C to about 65-C and most preferably from about 55C to about 60-C.
The amount of the pharmaceutical composition administered depends upon the percent of active ingredients within its formula, which is a function of the amount of the volatile essential oil components required per dose, stability, release characteristics and other pharmaceutical parameters. Usually from about 150 mg/kg to about 3600 mg/kg per day, preferably from about 150 mg/kg to about 2000 mg/kg per day and most preferably from about 150 mg/kg per day to about 1000 mg/kg per day of the pharmaceutical composition is administered as described herein. This amount can be given in a single dose or, preferably, in multiple (two to six) doses repeatedly over the course of treatment. Generally, each individual dosage of the pharmaceutical compositions of the present invention range from about 100 mg/kg to about 600 mg/kg, preferably from about 75 mg/kg to about 300 mg/kg and most preferably from about 50 mg/kg to about 150 mg/kg. While dosages higher than the foregoing are effective to prevent cough, care must be taken, as with any drug, in some individuals to prevent adverse side effects.
- l- Z~17923 The compositions and methods described herein are used in an art recognized manner to provide antitUss~ve act~vity.
The following non-limlting e~amples illustrate embodiments of the subject invention wherein both essential and optional ingredients are combined. It is to be understood that these examples are for illus-trative purposes only and are not to be construed as limiting the scope of the invention thereto.
EXAMPLE I
A syrup for oral administration is prepared by combining the following ingredients:
Ingredient (wt %) Menthol (vapor pressure - lmm at 60'C) 0.1 Ethanol 10.0 Sucrose 45.0 Purified Water and Colorant q.s.
The above ingredients are combined to provide a solution (having a viscosity of about 100 cps) which is then heated to a temperature of about 60-C. 30 ml of this heated formulation are administered to an adult human in need of treatment, thereby reducing cough and conges-tion.
Substantially similar results are obtained when the mentholcomponent is replaced in whole or in part with acetic acid, benzoic acid, cinnamic acid, phenylacetic acid, benzyl alcohol, borneol, cinnamyl alcohol, citronellol, geraniol, linalool, phenylethyl al-cohol, terpineol, anisaldehyde, cinnamaldehyde, benzaldehyde, citral,piperonal, heliotrcpin, salicylaldehyde, vanillin, carvone, camphor, thujone, pulegone, bornyl acetate, methyl salicylate, benzyl benzoate, geranyl acetate, linalyl acetate, thymol, carvacrol, chavicol, ane-thole, eugenol, safrol, coumarin, indole, and mixtures thereof.
EXAMPLE II
A syrup for oral administration is prepared by combining the following ingredients:
Menthol 0.075%
Eucalyptus Oil 0.025%
Ethanol 5.0%
Propylene Glycol 10.0%
Sucrose 40.0%
Invert Syrup 30.0%
Water and Color q.s.
- 1 1 - 2~.-117923 The abo~e ingredients are combined to provlde a solution (having a viscosity of about 300 cps) which ls then heated to a temperature of about 60'C. 30 ml of this heated formulation are administered to an adult human in need of treatment, thereby reducing cough and conges-tion.
Substantially similar results are obtained when the propylene glycol component is replaced in whole or in part with water, simple syrup, polyethylene glycol, alcohol, corn syrup, invert sugar, gela-tin, ethyl oleate, cottonseed oil and sesame oil and mixtures thereof.
EXAMPEE II~
A syrup for oral administration is prepared by combining the following ingredients:
Inaredient WtX
Menthol a. 1%
Dextromethorphan HBr O.lX
Citric Acid 0.02~o Glycerin 10.0%
Invert Syrup (70%) 50.0%
Ethanol 5.0%
Purified Water and tolorant qs The citric acid is dissolved in the water and ethanol at room temperature. While stirring, the menthol, glycerin and dextromethor-phan HBr are added to this mixture and the color is added. The invert syrup is then added thereby producing a thick syrupy liquid (having a viscosity of about 200 cps). The resulting syrup is then heated to 60-C. 30 ml of this heated syrup is administered to an adult human in need of treatment, thereby reducing cough.
Substantially similar results are obtained when the dextro-methorphan is replaced in whole or in part with a therapeutically equivalent level of chlophedianol, carbetapentane, caramiphen, no-scapine, diphenhydramine, codeine, hydrocodone, hydromorphone, fomino-ben, their pharmaceutically-acceptable salts, and mixtures thereof.
EXAMPLE IV
A suspension for oral administration is prepared by combining the following ingredients:
-l2- Z~17923 Ingredient Amount Menthol 0.1%
Dextromethorphan HBr 0.1%
Pseudoephedrine hydrochloride 0.07%
S Microcrystalline cellulose and sodium carboxy methyl cellulose1.25%
Sucrose 45.0%
Glycerin 5-0%
Sorbitol solution (70%) 20.0%
Potassium sorbate 0.1%
Sodium saccharin 0.2%
Purified water and Colorant q.s.
The above ingredients are combined to produce a suspension (having a viscosity of about 350 cps), which is then heated to a temperature of 60-C. 30 ml of this heated formulation are administer-ed to an adult human in need of treatment, thereby reducing cough.
Substantially similar results are obtained when the dextromethor-phan is replaced in whole or in part with a therapeutically equivalent level of chlophedianol, carbetapentane, caramiphen, noscapine, diphen-hydramine, codeine, hydrocodone, hydromorphone, fominoben, theirpharmaceutically-acceptable salts, and mixtures thereof.
Substantially similar results are obtained when the pseudo-ephedrine hydrochloride is replaced in whole or in part with a thera-peutically equivalent level of phenylpropanolamine, phenylephrine, their pharmaceutically acceptable salts, and mixtures thereof.
WHAT IS CLAIMED IS:
Claims (20)
1. An oral pharmaceutical composition for the treatment of cough comprising:
(a) from about 0.01% to about 0.25% of a volatile essential oil component having a vapor pressure of from about 0.05mm to about 15.0mm at 60°C; and (b) from about 50% to about 99% of a pharmaceutically acceptable oral carrier having a viscosity of from about 150 cps to about 800 cps wherein said pharmaceutical composition has a temperature of from about 35°C to about 70°C.
(a) from about 0.01% to about 0.25% of a volatile essential oil component having a vapor pressure of from about 0.05mm to about 15.0mm at 60°C; and (b) from about 50% to about 99% of a pharmaceutically acceptable oral carrier having a viscosity of from about 150 cps to about 800 cps wherein said pharmaceutical composition has a temperature of from about 35°C to about 70°C.
2. An oral pharmaceutical composition according to Claim 1 wherein said pharmaceutically acceptable carrier has a viscosity of from about 150 cps to about 700 cps and wherein said composition comprises from about 0.02% to about 0.2% of the volatile essen-tial oil component selected from the group consisting of acetic acid, benzoic acid, cinnamic acid, phenylacetic acid, benzyl alcohol, borneol, cinnamyl alcohol, citronellol, geraniol, linalool, menthol, phenylethyl alcohol, terpineol, anisaldehyde, cinnamaldehyde, benzaldehyde, citral, piperonal, heliotropin, salicylaldehyde, vanillin, carvone, camphor, thujone, pulegone, bornyl acetate, methyl salicylate, benzyl benzoate, geranyl acetate, linalyl acetate, thymol, carvacrol, chavicol, anethole, eucalyptol, eugenol, safrol, eucalyptus oil, peppermint oil, cuminal, coumarin, indole, and mixtures thereof.
3. An oral pharmaceutical composition according to Claim 2 wherein said pharmaceutically acceptable carrier has a viscosity of from about 150 cps to about 600 cps and wherein said composition comprises from about 0.05% to about 0.15% of the volatile essen-tial oil component and wherein said volatile essential oil component is selected from the group consisting of menthol, eucalyptus oil, eugenol, camphor, thymol, anethole, eucalyptol, peppermint oil, cuminal, and citral and mixtures thereof.
4. An oral pharmaceutical composition according to Claim 2 which further comprises a safe and effective amount of an oral anti-tussive drug.
5. An oral pharmaceutical composition of Claim 4 wherein said oral antitussive drug is selected from the group consisting of dextro-methorphan, chlophedilanol, carbotapantane, caramiphen, noscapine, diphenhydramine, codeine, hydrocodonet hydromorphone, fominoben, their pharmaceutically-acceptable salts, and mixtures thereof.
6. An oral pharmaceutical composition according to Claim 5 wherein said composition has a temperature of from about 50°C to about 65°C and wherein said oral antitussive drug is selected from the group consisting of dextromethorphan, codeine, diphenhydramine, pharmaceutically-salts thereof and mixtures thereof.
7. An oral pharmaceutical composition according to Claim 6 wherein said oral antitussive drug is selected from the group consisting of dextromethorphan, codeine, pharmaceutically acceptable salts thereof and mixtures thereof.
8. An oral pharmaceutical composition according to Claim 3 which further comprises a safe and effective amount of an oral decon-gestant drug.
9. An oral pharmaceutical composition according to Claim 8 wherein said oral decongestant drug is selected from the group consisting of pseudoephetrine hydrochloride, phenylpropanolamine hydrochlo-ride, phenylephrine hydrochloride and ephedrine hydrochloride and mixtures thereof.
10. An oral pharmaceutical composition according to Claim 5 which further comprises a safe and effective amoujnt of an oral decon-gestant drug.
11. An oral pharmaceutical composition according to Claim 10 wherein said oral decongestant drug is selected from the group consisting of pseudoephedrine hydrochloride, phenylpropanolamine hydrochlo-ride, phenylephrine hydrochloride and ephedrine hydrochloride and mixtures thereof.
12. An oral pharmaceutical composition according to Claim 11 which further comprises from about 5 v/v% to about 25v/v% of a solvent selected from the group consisting of propylene glycol, water, simple syrup, polyethylene glycol, alcohol, corn syrup, invert sugar, gelatin, propylene glycol, ethyl oleate, cottonseed oil and sesame oil and mixtures thereof.
13. An oral pharmaceutical composition according to Claim 10 which further comprises from about 1% to about 25%. of ethanol.
14. An oral pharmaceutical composition according to Claim 12 which further comprises from about 5% to about 25% ethanol.
15. An oral pharmaceutical composition according to Claim 12 in the form of a syrup, emulsion, suspension or solution.
16. An oral pharmaceutical composition according to Claim 14 in the form of a syrup, emulsion, suspension or solution.
17. A method for the treatment of cough in humans or animals which comprises administering to a human or animal in need of such treatment the pharmaceutical composition of Claim 1.
18. A method for the treatment of cough in humans or animals which comprises administering to a human or animal in need of such treatment the pharmaceutical composition of Claim 5.
19. A method for the treatment of cough in humans or animals which comprises administering to a human or animal in need of such treatment the pharmaceutical composition of Claim 11.
20. A method for the treatment of cough in humans or animals which comprises administering to human or animal in need of such treatment the pharmaceutical composition of Claim 15.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US36198489A | 1989-06-06 | 1989-06-06 | |
| US361,984 | 1989-06-06 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2017923A1 true CA2017923A1 (en) | 1990-12-06 |
Family
ID=23424216
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA 2017923 Abandoned CA2017923A1 (en) | 1989-06-06 | 1990-05-30 | Heated oral antitussive compositions |
Country Status (2)
| Country | Link |
|---|---|
| CA (1) | CA2017923A1 (en) |
| GB (1) | GB2244645B (en) |
Families Citing this family (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| IL161545A0 (en) * | 2001-11-16 | 2004-09-27 | Cutanix Corp | Pharmaceutical and cosmetic compositions containing oxy group-bearing aromatic aldehydes |
| US8246969B2 (en) | 2001-11-16 | 2012-08-21 | Skinmedica, Inc. | Compositions containing aromatic aldehydes and their use in treatments |
| JP6378878B2 (en) | 2011-01-07 | 2018-08-22 | アラーガン、インコーポレイテッドＡｌｌｅｒｇａｎ，Ｉｎｃｏｒｐｏｒａｔｅｄ | Melanin modified composition and method of use |
| CN116920015A (en) * | 2023-06-30 | 2023-10-24 | 杭州汉光生物医药科技有限公司 | Novel menthol eucalyptus oil cough relieving spray and application thereof |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB829537A (en) * | 1958-08-27 | 1960-03-02 | Upjohn Co | Improvements in or relating to therapeutic terpin hydrate suspensions |
| GB1051240A (en) * | 1964-11-06 |
-
1990
- 1990-05-30 CA CA 2017923 patent/CA2017923A1/en not_active Abandoned
- 1990-06-02 GB GB9012351A patent/GB2244645B/en not_active Expired - Fee Related
Also Published As
| Publication number | Publication date |
|---|---|
| GB2244645B (en) | 1994-07-13 |
| GB9012351D0 (en) | 1990-07-25 |
| GB2244645A (en) | 1991-12-11 |
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