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WO1994008550A1 - Compositions anesthesiques - Google Patents

Compositions anesthesiques Download PDF

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Publication number
WO1994008550A1
WO1994008550A1 PCT/US1993/008957 US9308957W WO9408550A1 WO 1994008550 A1 WO1994008550 A1 WO 1994008550A1 US 9308957 W US9308957 W US 9308957W WO 9408550 A1 WO9408550 A1 WO 9408550A1
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WO
WIPO (PCT)
Prior art keywords
composition
carbon atoms
cooling agent
composition according
hydrogen
Prior art date
Application number
PCT/US1993/008957
Other languages
English (en)
Inventor
Peter Close
Carmelita Macklin Russell
James Grigg Upson
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
Priority claimed from GB939306937A external-priority patent/GB9306937D0/en
Application filed by The Procter & Gamble Company filed Critical The Procter & Gamble Company
Priority to AU51348/93A priority Critical patent/AU5134893A/en
Publication of WO1994008550A1 publication Critical patent/WO1994008550A1/fr

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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
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/0053—Mouth and digestive tract, i.e. intraoral and peroral administration
    • A61K9/0056—Mouth soluble or dispersible forms; Suckable, eatable, chewable coherent forms; Forms rapidly disintegrating in the mouth; Lozenges; Lollipops; Bite capsules; Baked products; Baits or other oral forms for animals
    • 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

Definitions

  • This invention relates to anaesthetic compositions for application to or consumption by the human body.
  • it relates to anaesthetic compositions which exhibit effective anaesthetic activity in the throat while at the same time reduce the feeling of numbness in the mouth and throat associated with use of anaesthetics.
  • Local anaesthetics are well known in the art for fne treatment of sore throats. They have been incorporated into pharmaceutical compositions and administered in the form of sprays, gargles, lozenges and tablets.
  • Local anaesthetics reduce pain by impairing the generation and conduction of the nerve impulses by slowing depolarisation. This results from blocking of the large transient increase in permeability of the cell membrane to sodium ions that follows initial depolarisation of the membrane. Local anaesthetics also reduce the permeability of the resting axon to potassium and to sodium ions.
  • a widely used local anaesthetic is lignocaine. The site of action of lignocaine is on a specific receptor site in the sodium channel.
  • CH-A-657,777 and CH-A-643,144 disclose compositions containing lignocaine and antacids for the treatment of oesophagitis.
  • Another widely used local anaesthetic is benzocaine. Both benzocaine and lignocaine have been used as anaesthetics in lozenge and spray forms of dosage.
  • AU-A-8,943,891 discloses a solid dose form, preferably a lozenge, for appetite suppression containing benzocaine or lignocaine and a peppermint flavour.
  • Administration of an anaesthetic to the taste receptors in the mouth by slow dissolution of chewing reduces nervous transmission to the hypothalamus and suppresses the appetite control centre.
  • EP-A-0,431,376 discloses a lozenge for sustained release treatment of sore throats comprising hydrogenated isomaltulose and an active ingredient which can be an anaesthetic such as benzocaine.
  • US-A-4,917,894 discloses an oral anaesthetic composition in the form of a liquid or a lozenge preferably comprising dyclonine and an anaesthetic selected from hexylresorcinol and benzocaine;
  • anaesthetic compositions which while providing effective sore throat pain relief, also reduce the feeling of numbness associated with anaesthetics.
  • anaesthetic composition which also reduces the feeling of numbness associated with anaesthesia and enhances the perceived feeling of pain relief.
  • compositions of various types have incorporated within them components which provide a cooling sensation to mucosal membranes and/or to skin.
  • Such compositions include toothpastes, mouthwashes, perfumes, lotions, shaving cream, post shaving preparations, shampoos, antiperspirants, deodorants, beverages, chewing gum, tobacco products, and pharmaceutical products among many others.
  • menthol is a physiological effect due to the direct action of menthol on the nerve endings of the human body responsive for the detection of hot or cold and is not due to latent heat of evaporation. It is believed that the menthol acts as a direct stimulus on the cold receptors at the nerve endings which in turn stimulate the central nervous system.
  • N,N-Dimethyl 2-ethylbutanamide is reported as having a minty odour and refreshing effect, and the minty odour of N,N-diethyl 2£- ⁇ imethylpropanamide is referred to.
  • a simitar effect is reported for N,N-diethyl 2-ethylbutanamide in Berichte 39, 1223, (1908).
  • a minty odour has also been reported for 2,4,6-trimethylheptan-4-ol and 2,4,6- trimethyl help-2-en-4-ol in perfumes-Cosmetiques-Svon, May 1956, pp. 17-20.
  • Carboxamides have also been disclosed for use in a variety of compositions. Two patents describing such materials and compositions are US-A-4,136,163, January 23, 1979 to Watson et al. and US-A- 4,230,688, October 28, 1980 to Rowsell et al.
  • EP-B-0,080,148 discloses the physiological cooling agent 3-1-menthoxy propan-l,2-diol (MPD), which is a monoglycerin derivative of 1-menthol.
  • the present invention provides an anaesthetic composition having enhanced consumer perception of pain relief while at the same reducing the unpleasant feeling of numbness associated with anaesthetics.
  • composition for application to or consumption by the human body comprising:
  • composition of a pharmaceutically-acceptable local anaesthetic from about 0.01 % to about 1 % by weight of composition of a pharmaceutically-acceptable local anaesthetic, ii) from about 0.01 % to about 1 % by weight of composition of a physiological cooling agent, and, iii) a carrier,
  • physiological cooling agent comprises one or more cooling agents having a threshold cooling value of less than about 100 ⁇ g and a molecular weight of greater than about 160.
  • a physiological cooling agent for the manufacture of a composition for reducing the feeling of numbness associated with anaesthesia wherein the physiological cooling agent comprises one or more cooling agents having a threshold cooling value of less than about lOO ⁇ g and a molecular weight of greater than about 160.
  • compositions herein contain, as essential ingredients, a pharmaceutically-acceptable local anaesthetic, a physiological cooling agent and a carrier.
  • Suitable pharmaceutically-acceptable local anaesthetics for use herein include benzocaine, methyl paraben, benzyl alcohol, salicyl alcohol, phenol, propyl paraben, lignocaine hydrochloride, dyclonine hydrochloride and hexylresorcinol.
  • the anaesthetic is selected from amide and ester type anaesthetics. More preferably the anaesthetic is selected from benzocaine and lignocaine hydrochloride, most preferably lignocaine hydrpchloride.
  • the anaesthetic is preferably present in an amount of from about 0.01 % to about 1 % , more preferably from about 0.02% to about 0.5%, most preferably from about 0.05% to about 0.2% by weight of composition.
  • the physiological cooling agent herein comprises one or more cooling agents having a threshold cooling value of at least about lOO ⁇ g and a molecular weight of greater than about 160.
  • the cooling agent is selected from carboxamides, menthane esters and menthane ethers, and mixtures thereof, these being preferred from the viewpoint of providing optimum anaesthetic, numbing-suppression and consumer acceptability.
  • a composition for application to or consumption by the human body comprising:
  • composition of a pharmaceutically-acceptable local anaesthetic from about 0.01 % to about 1 % by weight of composition of a pharmaceutically-acceptable local anaesthetic, ii) from about 0.01 % to about 1 % by weight of composition of a physiological cooling agent, and, iii) a carrier,
  • physiological cooling agent comprises one or more cooling agents selected from carboxamides, menthane esters and menthane ethers, and mixtures thereof.
  • Suitable methane ethers for use herein are selected from those with the formula:
  • R5 is an optionally hydroxy substituted aliphatic radical containing up to 25 carbon atoms, preferably up to 5 carbon atoms, and where X is hydrogen or hydroxy, such as those commercially available under the trade name Takasago, from Takasago International Corporation.
  • a particularly preferred cooling agent for use in the compositions of the present invention is Takasago 10 [3-1-menthoxy propan-l,2-diol (MPD)].
  • MPP is a monoglycerin derivative of 1-menthol and has excellent cooling activity.
  • the carboxamides in US-A-4,136,163 are N-substituted-p-menthane-3- carboxamides. These compounds are 3-substituted-p-menthanes of the formula:
  • R' when taken separately, is hydrogen or an aliphatic radical containing up to 25 carbon atoms; R" when taken separately is hydroxy, or an aliphatic radical containing up to 25 carbon atoms, with the proviso that when R' is hydrogen R" may also be an aryl radical of up to 10 carbon atoms and selected from the group consisting of substituted phenyl, phenalkyl or substituted phenalkyl, naphthyl and substituted naphthyl, pyridyl; and R' and R", when taken together with the nitrogen atom to which they are attached, represent a cyclic or heterocyclic group of up to 25 carbon atoms, e.g. piperidino, morpholino etc.
  • aliphatic is intended to include any straight- chained, branched-chained or cyclic radieal free or aromatic unsaturation, and thus embraces alkyl; cycloalkyl, alkenyi, cyclo-alkenyl, alkynyl, hydroxyalkyl, acyloxyalkyl, alkoxy, alkoxyalkyl, aminoalkyl, acylaminoalkyl, carboxyalkyl and similar combinations.
  • R* and R when aliphatic are methyl, ethyl, propyl, buty isobutyl, n-decyl, cyclopropyl, cyclohexyl* " cyclopentyl, cycloheptylmethyl, 2-hydroxyethyl, 3-hydroxy-n-propyl, 6-hydroxy-n- hexyl, 2-aminoethyl, 2-acetoxyethyl, 2-ethylcarboxy ethyl, 4-hydroxybut- 2-ynyl, carboxymethyl etc.
  • R" is aryl
  • typical values are benzyl, naphthyl, 4-methoxyphenyl, 4- hydroxyphenyl, 4-methylphenyl, 3-hydroxy-4-methylphenyl, 4- flurophenyl, 4-nitrophenyl, 2-hydroxynaphthyl, pyridyl, etc.
  • the carboxamides of US-A-4,230,688 are certain acyclic tertiary and secondary carboxamides. These have the structure l 2 C* C0NR ' R • •
  • R 1 and R when taken separately, are each hydrogen, C1-C5 alkyl or C1-C8 hydroxyalkyl and provide a total of no more than 8 carbon atoms, with the proviso that when R' is hydrogen R" may also be alkylcarboxyalkyl of up to 6 carbon atoms; R' and R", when taken together, represent an alkylene group of up to 6 carbon atoms, the opposite ends of which group are attached to the amide nitrogen atom thereby to form a nitrogen heterocycle, the carbon chain of which may optionally be interrupted by oxygen; Ri is hydrogen or C1-C5 alkyl; and
  • R2 and R3 are each C1-C5 alkyl; with the provisos that (i) R ⁇ , R2 and R3 together provide a total of at least 5 carbon atoms, preferably from 5-10 carbon atoms; and (ii) when Rj is hydrogen, R2 is C2-C5 alkyl and R3 is
  • C3-C5 alkyl and at least one of R2 and R3 is branched , preferably in an alpha or beta position relative to the carbon atom marked (*) in the formula.
  • Suitable menthane esters for use herein are selected from those with the formula:
  • R4 is hydrogen, hydroxy or an aliphatic radical containing up to 25 carbon atoms.
  • the physiological cooling agent is preferably present in an amount of from about 0.01 % to about 1 %, more preferably from about 0.02% to about 0.5%, most preferably from about 0.05% to about 0.1 % by weight of composition.
  • Highly preferred cooling agents herein have a threshold cooling value less than that of 1 -menthol.
  • compositions of the present invention also comprise a carrier.
  • the carrier is chosen according to the particular form the compositions take.
  • the compositions herein are preferably in the form of lozenges or tablets.
  • the carrier is a sugar or sugar-free base.
  • Sugar-free lozenge compositions are substantially free of saccharose components such as sucrose, fructose etc. while the sugar-based lozenge compositions contain a natural sugar such as sucrose, glucose, fructose, high fructose corn syrup and invert sugar.
  • Both sugar-free lozenge compositions and sugar-based lozenge compositions can contain one or more sugar alcohols and can be supplemented by conventional candy ingredients such as one or more flavouring agents, colouring agents and/or artificial sweetening agents.
  • Suitable sugar alcohols herein include sorbitol, manrritol, xylitol, maltitol and hydrogenated starch and glucose syrups produced by catalytic hydrogenation of carbohydrate syrups to the point where all carbohydrate end groups are reduced to alcohols.
  • a suitable hydrogenated starch hydrolysate includes from about 5% to about 10% sorbitol, from about 25% to about 75% maltitol and from about 20% to about 40% hydrogenated higher sac char ides.
  • Typical hydrogenated starch hydrolysates are Lycasin (RTM) or Maltidex (RTM) 100.
  • Candy compositions can contain up to about 95% natural sugar and/or sugar alcohol, especially maltitol, sorbitol, mixtures of sorbitol and maltitol, mannitol or other sugar alcohols.
  • compositions can additionally comprise menthol in an amount of from about 0.01 % to about 10%, preferably from about 0.02% to 0.5%, by weight.
  • the compositions can also contain other ingredients such as colouring agents, flavouring agents, preservatives and/or artificial sweetening agents, in order to provide a palatable preparation.
  • Suitable flavouring agents include synthetic flavour oils and/or oils derived from plants, leaves, flowers, fruits and so forth, and combinations thereof.
  • Representative flavour oils include spearmint oil, cinnamon oil, oil of wintergreen (methylsalicylate), eucalyptus and peppermint oils.
  • Also useful are artificial, natural or synthetic fruit flavours such as citrus oil including lemon, orange, grape, lime and grapefruit, and fruit essences including apple, strawberry, cherry, blackcurrent, pineapple and so forth.
  • flavouring agents and/or flavour enhancers employed is normally a matter of preference subject to such factors as flavour type, base type and strength desired. In general, amounts of about 0.05% to about 3.0% by weight of final composition are useable with amounts of about 0.3% to about 1.5% being preferred and about 0.7% to about 1.2% being more preferred.
  • artificial Sweeteners well-known in the art can be added to the compositions of the invention.
  • Suitable artificial sweeteners encompass water-soluble sweeteners such as the soluble saccharin salts, i.e., sodium or calcium saccharin salts, cyclamate salts, such as the sodium salt and the like, and the free acid form of saccharin; dipeptide based sweeteners such-as L-aspartyl-L-phenylalanine methyl ester fend materials described in US-A-3,392,131; dihydrochalcone; glycyrrhizin Stevia rebaudiana (Stevioside); and the synthetic sweetener 3,6-dihydro-6-methyl-l,l,2,3- oxathiazin-4-one-2,2-dioxide, particularly the potassium (Acesulfame-K), sodium and calcium salts thereof as described in DE-A-2,001,017.
  • water-soluble sweeteners such as the soluble saccharin salt
  • Artificial sweeteners are generally used in amounts of from about 0.005% to about 5% and most preferably from about 0.05% to about 1 % by weight of the final composition.
  • Colouring agents can be added to the compositions. Suitable colouring agents include FD&C (Food, Drug & Cosmetic) dyes such as Blue #1 or #2, FD&C Red #3 plus #40, FD&C Yellow #5 or #6, titanium dioxide or blends of these dyes selected to produce the desired colours.
  • FD&C Food, Drug & Cosmetic
  • natural colours such as cermine annatto beta carotene, turmeric, beet, grape skin extract, caramel, and blends thereof may by used as the colourant.
  • Typical use levels for the colouring agent range from 0.01 to 0.03% for synthetic dyes with levels of from 0.1 to 1.0% for the natural colourants.
  • organic acids such as citric, malic, maleic, fumaric, succinic, adipic and tartaric acids can be added to lozenge formulations for the purpose of providing tartness.
  • compositions of the invention can additionally comprise one or more pharmaceutically-acceptable drugs.
  • drugs include antipyretic and analgesic agents, antiphlogistics, antiarrhythmics, hypo tensors, vasodilators, anticholinergics, antiarteriosclerotics, agents for circulatory systems, antitussives, expectorants, ulcer preventives, enzyme preparations, anti- malignants, chemotherapeutic agents, antihistamine agents, enzyme preparations, and mouth disinfection agents, steroidal anti-inflammatory agents, non-steroidal anti-inflammatory agent, anti-allergic agents, vasoconstrictors, and mixtures thereof.
  • The-present invention also relates to the use of a physiological cooling agent for the manufacture of a composition for reducing the feeling of numbness associated with anaesthesia wherein the physiological cooling agent comprises one or more cooling agents having a threshold cooling value of less than about lOO ⁇ g and a molecular weight of greater than about 160.
  • the present invention further relates to the use of a physiological cooling agent for the manufacture of a composition for reducing the feeling of numbness associated with anaesthesia
  • the physiological cooling agent comprises one or more cooling agents selected from carboxamides, menthane esters and menthane ethers, and mixtures thereof.
  • the following test procedure can be used as a means to identify compounds having a physiological cooling activity and herein referred to as cold receptor stimulants. This test is intended purely as a means for identifying compounds having a physiological cooling agent activity and useful in the present invention and for giving an indication of the different relative activities of the compounds, as between themselves and as compared with menthol, when applied in particular manner to a particular part of the body.
  • results are not necessarily indicative of the activity of these compounds in other formulations and other parts of the body where other factors come into play.
  • a controlling factor in the onset of cooling effect, its intensity and longevity will be the rate of penetration of the compounds through the epidermis and this will vary in different locations on the human body.
  • the formulation of actual products according to this invention will therefore be done largely on an empirical basis although the test results and other figures given herein will be useful as a guide, particularly in the formulation of products for oral administration, since the test procedure to be described involves oral application of the compound.
  • a similar test may, of course, be devised for the purposes of measuring the relative activities of the compounds of another area of the body, for example, the face or forearm, and this will be a useful guide in the choice of compounds to be used in preparations for external topical usage.
  • test procedure is done on a statistical basis. This is necessary since sensitivity to these compounds will vary not only from compound to compound and from one part of the body to another, but also from one individual to another. Tests of this nature are commonly used in the testing of the organoleptic properties e.g. taste and smell of organic and inorganic compounds, see Kirk- Othmer: Encyclopedia of Chemical Technology, 2nd Ed. (1967) Vol. 14, pages 336-344.
  • test procedure is aimed at determining the minimum quantity of the test compound required to product a noticeable cooling effect in a person of average sensitivity, this minimum quantity being termed the threshold for that particular compound.
  • the tests are carried out on a selected panel of 6 people of median sensitivity to 1-menthol.
  • the second test square will contain 1.O ⁇ g, the third 0.5 ⁇ g, and so on. Each quantity is tested on the tongue at least 10 times.
  • the thresholds to cold receptor stimulus by 1 -menthol are determined for each individual of the panel, the threshold for each individual being that amount of 1- menthol for which, in a series of not less than 10 test applications,- a cooling effect is reported 50% of the time.
  • Six panel members are now selected whose threshold to 1 -menthol is in the range 0.1 ⁇ g to lO ⁇ g and whose average threshold is approximately 0.25 ⁇ g, this select panel being regarded as the test panel of average sensitivity.
  • compositions of the present invention are illustrated by the following Examples. Examples
  • Lozenges are prepared for the formulation below using conventional hard candy manufacturing equipment.
  • sucrose/glucose 60:40 to 100
  • lozenge compositions of the above examples provide effective anaesthetic activity in the throat while reducing the perceived feeling of numbness associated with the anaesthetic.

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Nutrition Science (AREA)
  • Physiology (AREA)
  • Zoology (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicinal Preparation (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)

Abstract

Compositions anesthésiques comprenant un anesthésique local pharmaceutiquement acceptable, un agent refroidissant physiologique et un excipient. Ces compositions réduisent la sensation d'engourdissement associée aux anesthésiques et accroissent la sensation de soulagement des douleurs chez le patient.
PCT/US1993/008957 1992-10-09 1993-09-21 Compositions anesthesiques WO1994008550A1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
AU51348/93A AU5134893A (en) 1992-10-09 1993-09-21 Anaesthetic compositions

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
US95501392A 1992-10-09 1992-10-09
US07/955,013 1992-10-09
GB9306937.5 1993-04-02
GB939306937A GB9306937D0 (en) 1993-04-02 1993-04-02 Anaestetic compositions

Publications (1)

Publication Number Publication Date
WO1994008550A1 true WO1994008550A1 (fr) 1994-04-28

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PCT/US1993/008957 WO1994008550A1 (fr) 1992-10-09 1993-09-21 Compositions anesthesiques

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AU (1) AU5134893A (fr)
MX (1) MX9306296A (fr)
WO (1) WO1994008550A1 (fr)

Cited By (10)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5698181A (en) * 1994-12-09 1997-12-16 Warner-Lambert Company Breath-freshening edible compositions comprising menthol and an N-substituted-P-menthane carboxamide and methods for preparing same
WO1998000168A1 (fr) * 1996-07-02 1998-01-08 Novartis Consumer Health S.A. Composition topique contenant une combinaison de composes antihistaminiques et de composes terpenoides
WO1998001134A1 (fr) * 1996-07-10 1998-01-15 Novartis Consumer Health S.A. Combinaisons pharmaceutiques de composes antihistaminiques et de terpenoides destinees a etre administrees par voie orale
WO1998002182A1 (fr) * 1996-07-12 1998-01-22 Novartis Consumer Health S.A. Combinations pharmaceutiques orales d'anti-inflammatoires non steroïdiens et de terpenoïdes
WO1998047483A1 (fr) * 1997-04-21 1998-10-29 The Procter & Gamble Company Compositions pour dragees
WO1998047484A1 (fr) * 1997-04-21 1998-10-29 The Procter & Gamble Company Dragee fourree
WO1998047482A1 (fr) * 1997-04-21 1998-10-29 The Procter & Gamble Company Compositions adoucissantes pour la gorge
EP1186289A2 (fr) * 2000-09-12 2002-03-13 Takasago International Corporation Méthode et agent pour mieux diffuser et faire durer un parfum
US7078066B2 (en) 1997-09-18 2006-07-18 Wm. Wrigley Jr. Company Chewing gum containing physiological cooling agents and method of making
US9956211B2 (en) 2011-04-29 2018-05-01 Moberg Pharma Ab Pharmaceutical compositions comprising a local anaesthetic such as bupivacaine for local administration to the mouth or throat

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3991178A (en) * 1973-07-13 1976-11-09 Lever Brothers Company Menthyl ester of N-acetylglycine and oral compositions containing same
US4136163A (en) * 1971-02-04 1979-01-23 Wilkinson Sword Limited P-menthane carboxamides having a physiological cooling effect
US4230688A (en) * 1972-04-18 1980-10-28 Wilkinson Sword Limited Acyclic carboxamides having a physiological cooling effect
US4459425A (en) * 1981-11-20 1984-07-10 Takasago Perfumery Co., Ltd. 3-Levo-Menthoxypropane-1,2-diol

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4136163A (en) * 1971-02-04 1979-01-23 Wilkinson Sword Limited P-menthane carboxamides having a physiological cooling effect
US4230688A (en) * 1972-04-18 1980-10-28 Wilkinson Sword Limited Acyclic carboxamides having a physiological cooling effect
US3991178A (en) * 1973-07-13 1976-11-09 Lever Brothers Company Menthyl ester of N-acetylglycine and oral compositions containing same
US4459425A (en) * 1981-11-20 1984-07-10 Takasago Perfumery Co., Ltd. 3-Levo-Menthoxypropane-1,2-diol

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
"Handbook of Nonprescription Drugs", 8th-Edition, Published 1986, by AM. PHARM. ASSO. (WASH. D.C.), pp. 162-164. *
"Physician's Desk Reference for Nonprescription Drugs", Published 1985, by EDWARD R. BARNHART, see pp. 607 and 672. *

Cited By (14)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5698181A (en) * 1994-12-09 1997-12-16 Warner-Lambert Company Breath-freshening edible compositions comprising menthol and an N-substituted-P-menthane carboxamide and methods for preparing same
WO1998000168A1 (fr) * 1996-07-02 1998-01-08 Novartis Consumer Health S.A. Composition topique contenant une combinaison de composes antihistaminiques et de composes terpenoides
WO1998001134A1 (fr) * 1996-07-10 1998-01-15 Novartis Consumer Health S.A. Combinaisons pharmaceutiques de composes antihistaminiques et de terpenoides destinees a etre administrees par voie orale
WO1998002182A1 (fr) * 1996-07-12 1998-01-22 Novartis Consumer Health S.A. Combinations pharmaceutiques orales d'anti-inflammatoires non steroïdiens et de terpenoïdes
WO1998047482A1 (fr) * 1997-04-21 1998-10-29 The Procter & Gamble Company Compositions adoucissantes pour la gorge
WO1998047484A1 (fr) * 1997-04-21 1998-10-29 The Procter & Gamble Company Dragee fourree
WO1998047483A1 (fr) * 1997-04-21 1998-10-29 The Procter & Gamble Company Compositions pour dragees
US7078066B2 (en) 1997-09-18 2006-07-18 Wm. Wrigley Jr. Company Chewing gum containing physiological cooling agents and method of making
US7364761B2 (en) 1997-09-18 2008-04-29 Wm. Wrigley Jr. Company Chewing gum containing physiological cooling agents and method of preparing
EP1186289A2 (fr) * 2000-09-12 2002-03-13 Takasago International Corporation Méthode et agent pour mieux diffuser et faire durer un parfum
EP1186289A3 (fr) * 2000-09-12 2003-04-23 Takasago International Corporation Méthode et agent pour mieux diffuser et faire durer un parfum
US7538081B2 (en) 2000-09-12 2009-05-26 Takasago International Corporation Method and agent for enhancing diffusivity and long-lasting property of fragrance
US9956211B2 (en) 2011-04-29 2018-05-01 Moberg Pharma Ab Pharmaceutical compositions comprising a local anaesthetic such as bupivacaine for local administration to the mouth or throat
US10493068B2 (en) 2011-04-29 2019-12-03 Moberg Pharma Ab Pharmaceutical compositions comprising a local anaesthetic such as bupivacaine for local administration to the mouth or throat

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MX9306296A (es) 1994-06-30
AU5134893A (en) 1994-05-09

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