WO1997002273A1 - Warming compounds - Google Patents

Warming compounds Download PDF

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Publication number
WO1997002273A1
WO1997002273A1 PCT/US1996/010194 US9610194W WO9702273A1 WO 1997002273 A1 WO1997002273 A1 WO 1997002273A1 US 9610194 W US9610194 W US 9610194W WO 9702273 A1 WO9702273 A1 WO 9702273A1
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Prior art keywords
ether
vanillyl alcohol
group
alcohol
ethyl
Prior art date
Application number
PCT/US1996/010194
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English (en)
French (fr)
Inventor
Philip Lloyd Kupper
Original Assignee
The Procter & Gamble Company
Priority date (The priority date 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 date listed.)
Filing date
Publication date
Application filed by The Procter & Gamble Company filed Critical The Procter & Gamble Company
Priority to JP9505145A priority Critical patent/JPH11508593A/ja
Priority to AU62769/96A priority patent/AU6276996A/en
Priority to EP96921572A priority patent/EP0837862A1/de
Publication of WO1997002273A1 publication Critical patent/WO1997002273A1/en

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Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
    • C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
    • C07F9/02—Phosphorus compounds
    • C07F9/06—Phosphorus compounds without P—C bonds
    • C07F9/22—Amides of acids of phosphorus
    • C07F9/24—Esteramides
    • C07F9/2404—Esteramides the ester moiety containing a substituent or a structure which is considered as characteristic
    • C07F9/242—Esteramides the ester moiety containing a substituent or a structure which is considered as characteristic of hydroxyaryl compounds
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/55—Phosphorus compounds
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q19/00—Preparations for care of the skin
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
    • C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
    • C07F9/02—Phosphorus compounds
    • C07F9/06—Phosphorus compounds without P—C bonds
    • C07F9/08—Esters of oxyacids of phosphorus
    • C07F9/09—Esters of phosphoric acids
    • C07F9/12—Esters of phosphoric acids with hydroxyaryl compounds
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
    • C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
    • C07F9/02—Phosphorus compounds
    • C07F9/06—Phosphorus compounds without P—C bonds
    • C07F9/16—Esters of thiophosphoric acids or thiophosphorous acids
    • C07F9/165—Esters of thiophosphoric acids
    • C07F9/18—Esters of thiophosphoric acids with hydroxyaryl compounds
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2800/00—Properties of cosmetic compositions or active ingredients thereof or formulation aids used therein and process related aspects
    • A61K2800/20—Chemical, physico-chemical or functional or structural properties of the composition as a whole
    • A61K2800/24—Thermal properties
    • A61K2800/242—Exothermic; Self-heating; Heating sensation
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q11/00—Preparations for care of the teeth, of the oral cavity or of dentures; Dentifrices, e.g. toothpastes; Mouth rinses

Definitions

  • the present invention relates to novel compounds and compositions useful in providing a perceived sensation of warmth.
  • compositions comprising one or more phos ⁇ phate derivatives, and carrier materials wherein the compositions are in a form suitable for oral or topical administration.
  • These compositions preferably contain a safe and effective amount of one or more active materials such as those which provide nutritional, therapeutic, antimicrobial, pharmaceutical, medicinal, and/or aesthetic benefit, and those commonly used in health care products.
  • a wide variety of flavor, coolant and sweetening agents are used in consumer and health care products today.
  • Aesthetic qualities of these compositions such as taste, smell, mouthfeel, and after-taste are important concerns for consumer accept ⁇ ability. Products with poor flavor, a bad after-taste or other negative aesthetics may limit consumer acceptability initially or over an extended period of time, thereby limiting consumer usage and compliance with treatment regimens.
  • An additional aspect of consumer acceptability and compliance is the con- sumer's perception of efficacy. Consumer satisfaction with a product is likely to be increased if some type of sensory signal exists to remind the consumer that the product is working after ingestion, topical administration or expectoration.
  • certain phosphate derivatives comprising a warming component may be inco ⁇ orated into consumer or health care compositions to improve the perceived efficacy of such compositions and/or deliver pleasing aesthet ⁇ ics and high consumer acceptability. It has also been discovered that these composi ⁇ tions for oral or topical administration may be formulated to further include a safe and effective amount of one or more pharmaceutical actives. These compositions provide sustained warming activity. These phosphate derivatives also serve in providing a sensory signal to the user.
  • the present invention relates to a compound having the formula:
  • R is a warming component; wherein R' and R" are independently selected from the group consist ⁇ ing of R, an adherent component, M 4" , M “ “ , M 4"4 " C + , and hydro ⁇ gen; wherein X, X 1 , X" are independently selected from the group consist ⁇ ing of oxygen, nitrogen, and sulfiir; wherein n is an integer from 1 to 3.
  • the present invention further relates to oral or topical compositions contain ⁇ ing these compounds.
  • the phosphate derivatives of the present invention may be formulated by phosphorylating at least one warming component. These compounds also include linking at least one warming component to an adherent component via a phosphate bridge. In addition, pyrophosphate and triphosphate groupings may be substituted for the phosphate group. A warming component may also be linked to phosphorous via two functional groups or attachment sites. Furthermore, the phosphate deriva ⁇ tives described above may be bound via Coulombic interaction with charged com- pounds or materials, including polymers.
  • compositions containing these compounds may deliver the desired warming qualities through the action of the phosphate derivative itself. These compositions may also provide a sustained or delayed effect since release ofthe warming compo ⁇ nent from the molecule does not occur until cleavage of the phosphate from the warming agent by phosphatase enzymes. Without being limited by theory, it is believed that this sustained or delayed release profile provides improved actual and/or perceived efficacy.
  • the phosphatase enzymes may include, but are not limited to, acidic, basic, or pyro-phosphatases.
  • warming component refers to warming compounds having a hydroxy, amino, or thiol functionality which is capable of forming an ester, amido, or thioester linkage with a phosphorus(V) atom.
  • Preferred warming compo ⁇ nents may be selected from the group consisting of vanillyl alcohol n-butyl ether (TK- 1000 supplied by Takasago Perfumery Co., Ltd., Tokyo, Japan), vanillyl alcohol n- propyl ether, vanillyl alcohol isopropyl ether, vanillyl alcohol isobutyl ether, vanillyl alcohol n-amino ether, vanillyl alcohol isoamyl ether, vanillyl alcohol n-hexyl ether, vanillyl alcohol methyl ether, vanillyl alcohol ethyl ether, gingerol, shogaol, paradol, zingerone, capsaicin, dihydrocap
  • M+ refers to physiologically relevant metal cations.
  • physiologically relevant metal cations refers to metal cations that are significant to the organic or bodily processes of a human or lower animal.
  • Preferred “M+” cations are sodium and potassium.
  • Pre ⁇ ferred “M++” cations are calcium, zinc, magnesium, manganese, copper, and tin. The preferred among "M+++” cation is iron.
  • C+ refers to a cation.
  • a cation as used herein refers to cations that contain positively charged nitrogen, phosphorus, oxygen, or sul ⁇ fur atoms. Such cations may contain more than one positively-charged site and in the case of oligomers or polymers containing nitrogen, phosphorus, oxygen, or sulfur at ⁇ oms, many positively-charged centers may exist.
  • Preferred cations include ammo ⁇ nium, protonated amines such as protonated glucosamine, and partially or fiilly protonated amine-containing polymers such as protonated chitosan.
  • R is a warming component
  • R 1 and R" are independently selected from the group consisting of R, an adherent component, M+, M++, M+++, C+, and hydrogen;
  • X, X, and X" are independently selected from the group consisting of oxy ⁇ gen, nitrogen, and sulfur; and
  • n is an integer from 1 to 3.
  • R' may equal R", preferably wherein R* and R" are selected from the group consisting of calcium, zinc, magnesium, manganese, copper, iron and tin.
  • R is preferably selected from the group of vanillyl alcohol derivatives consisting of vanillyl alcohol n-butyl ether, vanillyl alcohol n- propyl ether, vanillyl alcohol isopropyl ether, vanillyl alcohol isobutyl ether, vanillyl alcohol n-amino ether, vanillyl alcohol isoamyl ether, vanillyl alcohol n-hexyl ether, vanillyl alcohol methyl ether and vanillyl alcohol ethyl ether;
  • R' and R" are independently selected from the group consisting of R (as described above), C12-C18 diacyl glycerol, partially hydrolyzed vinyl acetate-ethyl- ene co-polymer, cellulose, chitin,
  • the most preferred phosphate derivatives are vanillyl alcohol isoamyl ether monophosphate, vanillyl alcohol n-butyl ether monophosphate and vanillyl alcohol n- hexyl ether monophosphate.
  • the phosphate derivatives are used in the present invention at levels of from about 0.001% to about 25%, preferably from about 0.01% to about 15% by weight of the composition. Mixtures of the above described phosphate derivatives may also be used, improving the warming effect of the phosphate derivative. Carriers
  • compositions in which the aforedescribed warming compound find application are many and varied. These compositions include those for consumption by or application to the human body. Broadly speaking, these compositions can be divided into comestible and topical compositions, both terms being taken in their broadest possible sense. Thus comestible is to be taken as including not only food ⁇ stuffs and beverages taken into the mouth and swallowed, but also other orally ingested compositions taken for reasons other than their nutritional value, e.g., ingestion tablets, antacid preparations, laxatives etc. Comestible compositions also include edible compositions taken by mouth, but not necessarily swallowed, e.g. chewing gum.
  • Topical compositions include not only compositions such as per ⁇ fumes, powders and other toiletries, lotions, liniments, oils and ointments applied to the external surfaces of the human body, whether for medical or other reasons, but also compositions applied to, or which, in normal usage, come in contact with internal mucous membranes ofthe body, such as those ofthe nose, mouth, or throat, whether by direct or indirect application or inhalation, and thus include nasal and throat sprays, dentifrice, mouthwash and gargle compositions. Also included within the present invention are toilet articles such as cleansing tissues and toothpicks impregnated or coated with the active warming compound.
  • one or more warming compounds will usually be inco ⁇ orated into a carrier which may be completely inert or which may be or contain other active ingredients.
  • a carrier which may be completely inert or which may be or contain other active ingredients.
  • carriers including solids, liquids, emulsions, foams and gels.
  • Typical carriers for the warming com- pounds include aqueous or alcoholic solutions; oils and fats such as hydrocarbon oils, fatty acid esters, long chain alcohols and silicone oils; finely divided solids such as starch or talc; cellulosic materials such as paper tissue; low-boiling hydrocarbons and halohydrocarbons used as aerosol propellants; gums and natural or synthetic resins.
  • Edible or potable compositions including alcoholic and non-alcoholic beverages, confectionery, frostings, chewing gum, cachous, jellies.
  • Toiletries including after shave lotions, shaving soaps, creams and foams, toilet water, deodorants and antiperspirants, "solid colognes", toilet soaps, bath oils and salts, shampoos, hair oils, talcum powders, face creams, hand creams, sunburn lotions, cleansing tissues, dentifrices, toothpicks, dental floss, toothbrushes, mouthwashes, hair tonics, denture adhesives.
  • Medicaments including antiseptic ointments, liniments, lotions, decon- gestants, counter-irritants, cough mixtures, throat lozenges, antacid and indigestion preparations, oral analgesics. Particular preparations according to the invention are discussed in more detail below.
  • the edible and potable compositions of this invention will contain the warm ⁇ ing compound in combination with an edible carrier and usuaUy a flavoring or color ⁇ ing agent.
  • the particular effect of the warming compound is to create a warm sensation in the mouth, and in some cases even in the stomach, and therefore the compositions find particular utility in sugar-based confectionery such as hot choco ⁇ lates, boiled sweets and candy, jellies and in chewing gum.
  • the formulation of such confections will be by ordinary techniques and according to conventional recipes and as such forms no part of this invention.
  • the warming compound will be added to the final composition at a convenient point and in amount sufficient to produce the desired warming effect in the final product.
  • the amount will vary depending upon the particular composition, the degree of warming effect desired and the strength of other flavorants in the composition. Similar considerations apply to the formulation of beverages. Generally speaking the compositions will find most utility in carbonated or noncarbonated soft drinks, but may also be used in alcoholic beverages. Toiletries:
  • a major utility will be in after shave lotions, toilet water etc., where the compounds will be used in alcoholic or aqueous alcoholic solution, such solutions usually also containing a perfume or mild antiseptic or both.
  • Another field of utility will be in soaps, shampoos, bath oils etc. where the compositions will be used in combination with an oil or fat or a natural or synthetic surfactant e.g., a fatty acid salt or a lauroylsulphate salt, the composition usually also containing an essential oil or perfume.
  • the range of soap compositions will include soaps of all kinds, e.g., toilet soaps, shaving soaps, shaving foams etc.
  • a further class of toilet compositions into which the compositions may be inco ⁇ orated includes cosmetic creams and emollients, such creams and emollients usually comprising a base emulsion and optionally a range of ingredients such as wax, preservative, perfume, antiseptics, astringents, pigments etc. Also included within this class are lipstick compositions, such compositions usually comprising an oil and wax base into which the warming compound can be inco ⁇ orated along with the conventional ingredients, i.e., pigments, perfumes etc. Once again the formulation of such compositions is conventional.
  • compositions for oral hygiene containing the warming compound include mouthwash and dentifrice compositions and are preferred compositions.
  • the first will usually comprise an aqueous, alcoholic, or aqueous-alcoholic solution of an antiseptic often colored or flavored for palatability in an amount of from 0.001% to 1.0% by weight.
  • Dentifrice compositions may be of the powder, paste or liquid type and will usually comprise a finely divided abrasive or polishing material, e.g., precipitated chalk, silica, magnesium silicate, aluminum hydroxide or other similar materials well known in the art, and a detergent or foaming agent.
  • Optional ingredients which may also be included are flavoring agents and colorants, antiseptics, lubricants, thickeners, emulsifiers or plasticizers.
  • pyrophosphate salts such as those described in U.S. 4,515,772, May 7, 1985 to Parran et al, inco ⁇ o ⁇ rated herein by reference.
  • nonionic antimicrobials such as triclosan described in U.S. 4,894,220, January 16, 1990 to Nabi, et al. Both patents are inco ⁇ orated herein by reference. Examples of such antimicrobial agents include triclosan and other phenolic compounds.
  • Another agent which can be used in the present compositions is an alkali metal bicarbonate such as sodium bicarbonate. These can be used together with a peroxide compound in separate compartments such as disclosed in U.S. 4,849,213 and U.S. 4,528,180, both to Schaeffer, inco ⁇ orated herein by reference in its entirety.
  • Medicaments include sodium bicarbonate, sodium bicarbonate, and sodium bicarbonate.
  • the warming compounds may be used in a variety of oral medicines, nasal and throat sprays, and topical compositions, particularly where a counter-irritant is required.
  • Carriers inco ⁇ orating the compounds of the present invention may also contain pharmaceutically acceptable actives.
  • safe and effective amount as used herein means an amount that is effective to mitigate and/or treat the symptoms for which the pharmaceutically acceptable active is indicated in a human or mammal without undue adverse side effects commensurate with a reasonable risk/benefit ratio.
  • Pharmaceutically acceptable actives useful in the present invention include actives selected from among the various groups of chemical compounds or materials suitable for oral administration and having a pharmacological action. Mixtures of various pharmaceutical actives may also be used. These pharmaceutically acceptable actives should be compatible with the other essential ingredients and compatible in combination with other included active materials or compounds and can be present at a level of from about 0.01% to about 90%, preferably from about 0.1% to about 75%, more preferably from about 1.0% to about 50% and most preferably from about 1.0% to about 25%.
  • Suitable pharmaceutically acceptable active materials or compounds may be selected from, but are not limited to: bronchodilators, ano- rexiants, antihistamines, nutritional supplements (such as vitamins, minerals, fatty acids, amino acids, and the like), laxatives, analgesics, antacids, H2-receptor antago ⁇ nists, antidiarrheals, decongestants, antitussives, antinauseants, antimicrobials, anti- fungals, antivirals, expectorants, anti-inflammatory agents, antipyretics, their pharma- ceutically acceptable salts and mixtures thereof.
  • salts derived from inorganic bases include sodium, potas ⁇ sium, lithium, ammonia, calcium, magnesium, ferrous, zinc, manganous, aluminum, ferric, manganic salts and the like.
  • Salts derived from pharmaceutically acceptable organic non-toxic bases include salts of primary, secondary, tertiary and quaternary amines, substituted amines including naturally occurring substituted amines, cyclic amines and basic ion exchange resins, such as triethylamine, tripropylamine, 2-di- methylaminoethanol, 2-diethylaminoethanol, lysine, arginine, histidine, caffeine, procaine, N-ethylpiperidine, hydrabamine, choline, betaine, ethylenediamine, glu ⁇ cosamine, methylglycamine, theobromine, purines, piperazine, piperidine, polyamine resins and the like.
  • basic ion exchange resins such as triethylamine, tripropylamine, 2-di- methylaminoethanol, 2-diethylaminoethanol, lysine, arginine, histidine, caffeine, procaine, N-eth
  • Preferred pharmaceutical actives for use in compositions inco ⁇ orating the compounds ofthe present invention include respiratory and GI actives selected from the group consisting of decongestants, antitussives, expectorants, analgesics, antihis ⁇ tamines, anticholinergics, antacids, H2-receptor antagonists, laxatives and antidiar ⁇ rheals.
  • decongestants useful in the compositions of the present inven ⁇ tion include pseudoephedrine, phenylpropanolamine, phenylephrine and ephedrine, their pharmaceutically acceptable salts, and mixtures thereof.
  • antitussives useful in the compositions of the present invention include dextrometho ⁇ han, chlopedianol, carbetapentane, caramiphen, noscapine, diphenhydramine, codeine, hydrocodone, hydromo ⁇ hone, their pharmaceutically ac ⁇ ceptable salts, and mixtures thereof.
  • expectorants also known as mucolytic agents
  • examples of expectorants useful in the pre ⁇ sent invention include: guaifenesin, te ⁇ in hydrate, ammonium chloride, N-acetylcys- teine, and ambroxol, their pharmaceutically acceptable salts, and mixtures thereof.
  • analgesics useful in the present invention include mo ⁇ hine, co ⁇ characteristic, meperidine, pentazocine, propoxyphene, acetaminophen, allopurinol, acetyl- salicylic acid, choline salicylate, ketoprofen, magnesium silicate, fenoprofen, ibupro ⁇ fen, indomethacin, naproxen, and many others and their pharmaceutically acceptable salts and mixtures thereof.
  • antihistamines useful in the present invention include brom- pheniramine, chlo ⁇ heniramine, clemastine, dexchlo ⁇ heniramine, diphenhydramine, doxylamine, promethazine, terfenadine, triprolidine and many others and their phar ⁇ maceutically acceptable salts and mixtures thereof.
  • Analgesics, decongestants, antihistamines, expectorants and antitussives, as well as their acceptable dosage ranges are described in U.S. Patent 4.783.465 to Sun ⁇ shine et al., issued November 8, 1988, and U.S. Patent 4.619.934 to Sunshine et al., issued October 28, 1986, which are inco ⁇ orated by reference herein.
  • gastrointestinal agents suitable for use in the present invention include: anticholinergics, including atropine, clidinium and dicyclomine; antacids, in ⁇ cluding aluminum hydroxide, bismuth subsalicylate, calcium carbonate and magaldrate; H2-receptor antagonists, including cimetidine, famotidine, nizatidine and ranitidine; laxatives, including phenolphthalein and casanthrol; and antidiarrheals including diphenoxylate and loperamide.
  • anticholinergics including atropine, clidinium and dicyclomine
  • antacids in ⁇ cluding aluminum hydroxide, bismuth subsalicylate, calcium carbonate and magaldrate
  • H2-receptor antagonists including cimetidine, famotidine, nizatidine and ranitidine
  • laxatives including phenolphthalein and casanthrol
  • antidiarrheals including diphenoxylate and loperamide
  • analgesics decongestants, antitussives, expecto ⁇ rants and antihistamines as well as bronchodilators, anorexiants, laxatives, antiemet- ics, antimicrobials, antibacterials, antifungals, anti-inflammatory agents, antivirals, antipyretics, nutritional supplements, anticholinergics, antacids, H2-receptor antago ⁇ nists, antidiarrheals and other miscellaneous gastrointestinal compounds and their ac- ceptable dosage ranges are described in Remington's Pharmaceutical Sciences, pp.
  • Additional warming agents may also be optionally inco ⁇ orated into the carriers of the present invention.
  • Suitable additional warming agents include ethyl alcohol, niacin, jambu, nicotinic acid, zingerone, vanillyl alcohol n-butyl ether, va ⁇ nillyl alcohol n-propyl ether, vanillyl alcohol isopropyl ether, vanillyl alcohol isobutyl ether, vanillyl alcohol n-amino ether, vanillyl alcohol isoamyl ether, vanillyl alcohol n-hexyl ether, vanillyl alcohol methyl ether, vanillyl alcohol ethyl ether, gingerol, methyl salicylate, shogaol paradol, zingerone, capsaicin, dihydrocapsaicin, nordihy- drocapsaicin, homocapsaicin, homodihydrocapsaicin,
  • fluid extracts may optionally be used: mustard seed, ginger, horseradish, chillies, jalapeno, pepper, capsicum, clove, cassia and mixtures thereof.
  • Pharmaceutically acceptable salts of the above men ⁇ tioned compounds may also be used as well as mixtures thereof.
  • Carriers of the present invention may also include compounds commonly referred as muco-adhesives.
  • Muco-adhesives most suitable for inco ⁇ oration have an adhesive strength (measured as work of adhesion) ranging generally from about 0.5 to about 10 Newton-sec, more preferable from about 1 to about 8 Newton-sec, and most preferable from 3 about to about 7 Newton-sec and tackiness ranging from about 1 to about 10 Newton as measured using the TA.XT2 Texture Analyzer (Scarsdale NY) instrument using a TA-25 2" diameter probe at 25°C.
  • Preferred mucoadhesives are polymers including the following hydrogels: poly(ethylene oxide), poly(ethylene glycol), poly(vinyl alcohol), poly(vinyl pyrrolidine), poly(acrylic acid), poly(hydroxy ethyl methacrylate), hydroxypropyl cellulose, hydroxypropyl methyl cellulose, hydroxyethyl methyl cellulose, hydroxyethyl cellulose, and chitosan and mixtures thereof.
  • the techniques, compositions for making hydrogels, and other fundamentals are discussed in "Hydrogels in Modem Medicine & Pharmacy Volume 1 (N. A. Peppas ed.) PP 1 to 171 (CRC Press, 1988) inco ⁇ orated herein by refer ⁇ ence.
  • polymers of poly(ethylene oxide) are available as Polyox® from Union Carbide Co ⁇ oration; poly(ethylene glycol), also known as PEG is available as Macrogol® from Ashland Co ⁇ .; poly (vinyl alcohol) is available from E. I. du Pont de Nemours & Co.; poly(vinyl pyrrolidine) is available from BASF Wyandotte Co ⁇ ., and GAF Co ⁇ .; hydroxypropyl cellulose is available as Klucel from Shin-Etsu Chem. Co.; hy ⁇ droxypropyl methyl cellulose or methyl hydroxypropylcellulose, and hydroxyethyl methyl cellulose are all available from Dow Chemicals.
  • Sodium carboxy methyl cellulose is available from FMC Co ⁇ .
  • the polymers are described in "Handbook of Pharmaceutical Excipients" jointly published by American Pharmaceutical Associa ⁇ tion- (Washington DC 20037, USA) and The Pharmaceutical Society of Greater England (London SE1 7JN, England), and is inco ⁇ orated by reference herein.
  • Cooling agents or a combination of cooling agents may also be inco ⁇ orated in the carriers ofthe present invention. Suitable cooling agents are those described in U.S. Patent 4.136.163. January 23, 1979, to Watson et al., U.S. Patents 4.032.661 and 4.230.688. June 28, 1977 and October 28, 1980, respectively, to Rowsell et al. and U.S.
  • Patent 5,266,592, November 30, 1993 to Grub et al. all of which are herein inco ⁇ orated by reference.
  • Particularly preferred cooling agents include N-ethyl-p- menthane-3-carboxamide (WS-3 supplied by Takasago Perfumery Co., Ltd., Tokyo, Japan) taught by the above inco ⁇ orated U.S. Patent 4.136.163 and N,2,3 -trimethyl- 2-isopropylbutanamide which is commercially available as WS-23 from Wilkinson Sword Limited and taught by the above inco ⁇ orated U.S. Patent 4.230.688.
  • WS-3 supplied by Takasago Perfumery Co., Ltd., Tokyo, Japan
  • An ⁇ other particularly preferred cooling agent is 3-1-menthoxypropane 1,2-diol (TK-10 supplied by Takasago Perfumery Co., Ltd., Tokyo, Japan). This material is described in detail in U.S. Patent 4.459.425. July 10, 1984 to Amano et al. and inco ⁇ orated herein by reference.
  • TK-10 3-1-menthoxypropane 1,2-diol
  • ingredients suitable for admixture with the compounds of the present invention include, but are not limited to: coloring agents; flavoring agents, including: vanilla, cherry, grape, cranberry, orange, peppermint, spearmint, anise, blueberry raspberry, banana, chocolate, caramel, strawberry, lemon, lime, menthol and ProsweetTM MM50 (a combination of natural and artificial flavors and propylene glycol, available from Virginia Dare Extract Co., Inc., Brooklyn, NY); sweeteners, including saccharin, dextrose, levulose, sucrose, fructose, cyclamate, mannitol, aspartame, and acesulfame K, along with many others; suspending agents, including xanthum gum, acacia gum, carboxymethylcellulose, starch and methylcellulose; preservatives; releasing agents, including polysorbate 80, sodium lauryl sulfate, vegetable oils and magnesium stearate; and water.
  • coloring agents including: vanilla, cherry, grape, cranberry,
  • COMPOUND USE Compositions inco ⁇ orating the compounds of the present invention are used in a conventional manner wherein the amounts of the product are what users gener ⁇ ally use.
  • the mixture is then added to 50 ml of a chilled (under nitrogen) aqueous solution containing 19.7 g of sodium bicarbonate.
  • the resulting solution is extracted with ether and acidified using 15.1 g of concentrated hydrochloric acid.
  • the acidified solution is again extracted with ether dried over anhydrous sodium sulfate. Removal ofthe ether under reduced pressure leaves a pale yellow oil which partially solidifies when dried overnight under high vacuum.
  • the partially solidified product can be further dried in a vacuum oven and purified by crystallization from an acetone/water mixture.
  • a soft gelatin capsule containing a concentrated liquid core composition is prepared from the following ingredients.
  • a soft gelatin mixture is prepared from the following ingredients. Ingredient Weight %
  • the above ingredients are combined in a suitable vessel and heated with mixing at about 65°C to form a uniform solution.
  • the resulting solution is used to prepare soft gelatin capsules contain ⁇ ing the liquid core composition formed above.
  • the resulting soft gelatin capsules are suitable for oral administration.

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  • Chemical & Material Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Organic Chemistry (AREA)
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PCT/US1996/010194 1995-07-05 1996-06-12 Warming compounds WO1997002273A1 (en)

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JP9505145A JPH11508593A (ja) 1995-07-05 1996-06-12 加温化合物
AU62769/96A AU6276996A (en) 1995-07-05 1996-06-12 Warming compounds
EP96921572A EP0837862A1 (de) 1995-07-05 1996-06-12 Ein wärmegefühl gebende verbindungen

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WO1998052545A1 (en) * 1997-05-22 1998-11-26 The Boots Company Plc Pharmaceutical compositions of flurbiprofen and burn-masking agent for treating sore throat
WO1998053825A1 (en) * 1997-05-27 1998-12-03 Algos Pharmaceutical Corporation Analgesic drug composition containing a capsaicinoid and potentiator therefor
GB2327041A (en) * 1997-07-09 1999-01-13 Smithkline Beecham Plc Topical Analgesic Composition
US5889057A (en) * 1995-11-22 1999-03-30 The Boots Company Plc Flurbiprofen lozenge for the treatment of sore throat
US6280762B1 (en) 1997-04-21 2001-08-28 The Procter & Gamble Company Center filled confectionery
US6306429B1 (en) 1997-04-21 2001-10-23 The Procter & Gamble Company Confectionery compositions
US6328982B1 (en) * 1998-08-04 2001-12-11 Takasago International Corporation Cool feeling composition
US6333024B1 (en) * 2000-01-20 2001-12-25 Colgate-Palmolive Company Effervescent dual component dentifrice having reduced sensory cues
US6391282B1 (en) * 1997-11-10 2002-05-21 Flemington Pharmaceutical Corp. Antihistamine sprays and ointments for relief of delayed contact dermatitis
US6432441B1 (en) 1997-04-21 2002-08-13 The Procter & Gamble Company Throat soothing compositions
US6780443B1 (en) * 2000-02-04 2004-08-24 Takasago International Corporation Sensate composition imparting initial sensation upon contact
WO2004112735A1 (ja) 2003-06-17 2004-12-29 Takasago International Corporation 洗髪及び身体洗浄剤組成物
US6838106B2 (en) 2000-12-12 2005-01-04 Takasago International Corporation Warming composition for food and drink or for oral care preparation
WO2006024018A2 (en) * 2004-08-24 2006-03-02 Neuromolecular Pharmaceuticals, Inc. Compositions for treating nociceptive pain
EP1693057A1 (de) * 2005-02-18 2006-08-23 The Procter & Gamble Company Coffein enthaltendes Konfekt
WO2007092823A2 (en) * 2006-02-07 2007-08-16 Whitehill Oral Technologies, Inc. Sialagogue coatings for interproximal devices
US20090155325A1 (en) * 2007-12-14 2009-06-18 Kimberly-Clark Worldwide, Inc. Formulation and products for promoting skin cleanliness and health
US7588793B1 (en) 1998-06-05 2009-09-15 Cadbury Adams Usa, Llc Enhanced flavoring compositions containing N-ethyl-p-menthane-3-carboxamide and method of making and using same
US8097271B2 (en) 2004-08-11 2012-01-17 Kraft Foods Global Brands Llc Warming compositions and delivery systems therefor
EP1885275A4 (de) * 2005-05-31 2012-04-18 Takasago Internat Corp Usa Topische wärmungszusammensetzung
WO2012148432A1 (en) 2011-04-28 2012-11-01 Acme Specialty Products, Llc Taste masking compositions and edible forms thereof
WO2014132163A1 (en) * 2013-02-28 2014-09-04 Pfizer Inc. Enhanced stability of novel liquid compositions
US8846007B2 (en) 2005-12-23 2014-09-30 Intercontinental Great Brands Llc Compositions providing a heating sensation for oral or dermal delivery
US9011946B2 (en) 2011-04-29 2015-04-21 Intercontinental Great Brands Llc Encapsulated acid, method for the preparation thereof, and chewing gum comprising same
US9402809B2 (en) 2006-03-16 2016-08-02 Niconovum Usa, Inc. Snuff composition
US9629832B2 (en) 2002-12-20 2017-04-25 Niconovum Usa, Inc. Physically and chemically stable nicotine-containing particulate material
US9661865B2 (en) 2006-09-29 2017-05-30 Mondelez Uk Holdings & Services Limited Chewing gum comprising polyethylene
US9668505B2 (en) 2013-02-18 2017-06-06 Acme Specialty Products, Llc Taste masking compositions and edible forms thereof for masking the taste of foods
US9717667B2 (en) 2012-12-20 2017-08-01 Colgate-Palmolive Company Oral care composition containing ionic liquids
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US11433037B2 (en) 2016-07-05 2022-09-06 Glaxosmithkline Consumer Healthcare Holdings (Us) Llc Oral dosage form containing a fast release exterior coating

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Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4134877A (en) * 1975-07-28 1979-01-16 Monsanto Company Flame retardant phosphoramidate compositions
US4515772A (en) * 1982-06-22 1985-05-07 The Procter & Gamble Company Oral compositions
WO1995007684A1 (en) * 1993-09-17 1995-03-23 The Procter & Gamble Company Pyrophosphate diesters for tartar control
WO1996015768A1 (en) * 1994-11-18 1996-05-30 The Procter & Gamble Company Oral compositions

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4134877A (en) * 1975-07-28 1979-01-16 Monsanto Company Flame retardant phosphoramidate compositions
US4515772A (en) * 1982-06-22 1985-05-07 The Procter & Gamble Company Oral compositions
WO1995007684A1 (en) * 1993-09-17 1995-03-23 The Procter & Gamble Company Pyrophosphate diesters for tartar control
WO1996015768A1 (en) * 1994-11-18 1996-05-30 The Procter & Gamble Company Oral compositions

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US5889057A (en) * 1995-11-22 1999-03-30 The Boots Company Plc Flurbiprofen lozenge for the treatment of sore throat
US6166083A (en) * 1995-11-22 2000-12-26 The Boots Company, Plc Suckable flurbiprofen lozenges for treatment of sore throat
US6432441B1 (en) 1997-04-21 2002-08-13 The Procter & Gamble Company Throat soothing compositions
US6280762B1 (en) 1997-04-21 2001-08-28 The Procter & Gamble Company Center filled confectionery
US6306429B1 (en) 1997-04-21 2001-10-23 The Procter & Gamble Company Confectionery compositions
WO1998052545A1 (en) * 1997-05-22 1998-11-26 The Boots Company Plc Pharmaceutical compositions of flurbiprofen and burn-masking agent for treating sore throat
WO1998053825A1 (en) * 1997-05-27 1998-12-03 Algos Pharmaceutical Corporation Analgesic drug composition containing a capsaicinoid and potentiator therefor
US6277398B1 (en) 1997-05-27 2001-08-21 Endo Pharmaceuticals Inc. Analgesic drug composition containing a capsaicinoid and potentiator therefor
GB2327041A (en) * 1997-07-09 1999-01-13 Smithkline Beecham Plc Topical Analgesic Composition
US6391282B1 (en) * 1997-11-10 2002-05-21 Flemington Pharmaceutical Corp. Antihistamine sprays and ointments for relief of delayed contact dermatitis
US7588793B1 (en) 1998-06-05 2009-09-15 Cadbury Adams Usa, Llc Enhanced flavoring compositions containing N-ethyl-p-menthane-3-carboxamide and method of making and using same
EP1393716A2 (de) * 1998-08-04 2004-03-03 Takasago International Corporation Zusammensetzung die einen kühlenden Effekt hervorruft
EP1393716A3 (de) * 1998-08-04 2004-03-17 Takasago International Corporation Zusammensetzung die einen kühlenden Effekt hervorruft
US6328982B1 (en) * 1998-08-04 2001-12-11 Takasago International Corporation Cool feeling composition
US6333024B1 (en) * 2000-01-20 2001-12-25 Colgate-Palmolive Company Effervescent dual component dentifrice having reduced sensory cues
US6780443B1 (en) * 2000-02-04 2004-08-24 Takasago International Corporation Sensate composition imparting initial sensation upon contact
US6890567B2 (en) 2000-02-04 2005-05-10 Takasago International Corporation Sensate composition imparting initial sensation upon contact
US6899901B2 (en) 2000-02-04 2005-05-31 Takasago International Corporation Sensate composition imparting initial sensation upon contact
SG127674A1 (en) * 2000-12-12 2006-12-29 Takasago Perfumery Co Ltd Warming composition for food and drink or for oralcare preparation
US6838106B2 (en) 2000-12-12 2005-01-04 Takasago International Corporation Warming composition for food and drink or for oral care preparation
US9629832B2 (en) 2002-12-20 2017-04-25 Niconovum Usa, Inc. Physically and chemically stable nicotine-containing particulate material
WO2004112735A1 (ja) 2003-06-17 2004-12-29 Takasago International Corporation 洗髪及び身体洗浄剤組成物
EP1639993A1 (de) * 2003-06-17 2006-03-29 Takasago International Corporation Shampoo oder örperreinigungszusammensetzung
EP1639993A4 (de) * 2003-06-17 2010-06-09 Takasago Perfumery Co Ltd Shampoo oder örperreinigungszusammensetzung
US8097271B2 (en) 2004-08-11 2012-01-17 Kraft Foods Global Brands Llc Warming compositions and delivery systems therefor
US8101208B2 (en) 2004-08-11 2012-01-24 Kraft Foods Global Brands Llc Sensate compositions and delivery systems therefor
WO2006024018A2 (en) * 2004-08-24 2006-03-02 Neuromolecular Pharmaceuticals, Inc. Compositions for treating nociceptive pain
WO2006024018A3 (en) * 2004-08-24 2006-07-20 Neuromolecular Pharmaceuticals Compositions for treating nociceptive pain
WO2006091409A1 (en) * 2005-02-18 2006-08-31 The Procter & Gamble Company Confectionery products containing caffeine
EP1693057A1 (de) * 2005-02-18 2006-08-23 The Procter & Gamble Company Coffein enthaltendes Konfekt
EP1885275A4 (de) * 2005-05-31 2012-04-18 Takasago Internat Corp Usa Topische wärmungszusammensetzung
US8846007B2 (en) 2005-12-23 2014-09-30 Intercontinental Great Brands Llc Compositions providing a heating sensation for oral or dermal delivery
WO2007092823A2 (en) * 2006-02-07 2007-08-16 Whitehill Oral Technologies, Inc. Sialagogue coatings for interproximal devices
WO2007092823A3 (en) * 2006-02-07 2008-07-10 Whitehill Oral Tech Inc Sialagogue coatings for interproximal devices
US9402809B2 (en) 2006-03-16 2016-08-02 Niconovum Usa, Inc. Snuff composition
US11547660B2 (en) 2006-03-16 2023-01-10 Niconovum Usa, Inc. Snuff composition
US11129792B2 (en) 2006-03-16 2021-09-28 Modoral Brands Inc. Snuff composition
US10219999B2 (en) 2006-03-16 2019-03-05 Niconovum Usa, Inc. Snuff composition
US9661865B2 (en) 2006-09-29 2017-05-30 Mondelez Uk Holdings & Services Limited Chewing gum comprising polyethylene
US20090155325A1 (en) * 2007-12-14 2009-06-18 Kimberly-Clark Worldwide, Inc. Formulation and products for promoting skin cleanliness and health
US9764168B2 (en) 2011-04-28 2017-09-19 Acme Specialty Products, Llc Taste masking compositions and edible forms thereof
WO2012148432A1 (en) 2011-04-28 2012-11-01 Acme Specialty Products, Llc Taste masking compositions and edible forms thereof
US9011946B2 (en) 2011-04-29 2015-04-21 Intercontinental Great Brands Llc Encapsulated acid, method for the preparation thereof, and chewing gum comprising same
US9737082B2 (en) 2011-04-29 2017-08-22 Intercontinental Great Brands Llc Chewing gum composition comprising encapsulated acid
US9717667B2 (en) 2012-12-20 2017-08-01 Colgate-Palmolive Company Oral care composition containing ionic liquids
US9668505B2 (en) 2013-02-18 2017-06-06 Acme Specialty Products, Llc Taste masking compositions and edible forms thereof for masking the taste of foods
WO2014132163A1 (en) * 2013-02-28 2014-09-04 Pfizer Inc. Enhanced stability of novel liquid compositions
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US9744133B2 (en) 2013-02-28 2017-08-29 Pfizer Inc. Enhanced stability of novel liquid compositions
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US9308166B2 (en) 2013-02-28 2016-04-12 Pfizer Inc. Enhanced stability of novel liquid compositions
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CN108187054B (zh) * 2013-02-28 2021-07-13 Pf消费者保健第一有限责任公司 新液体组合物的增强的稳定性
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US11433037B2 (en) 2016-07-05 2022-09-06 Glaxosmithkline Consumer Healthcare Holdings (Us) Llc Oral dosage form containing a fast release exterior coating
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CO4700531A1 (es) 1998-12-29
AU6276996A (en) 1997-02-05
JPH11508593A (ja) 1999-07-27
EP0837862A1 (de) 1998-04-29
AR003447A1 (es) 1998-08-05

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