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CN101330911A - Hydroxy-polycarboxylic acid esters: action on nerves and use on skin and mucocutaneous organs or sites - Google Patents

Hydroxy-polycarboxylic acid esters: action on nerves and use on skin and mucocutaneous organs or sites Download PDF

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CN101330911A
CN101330911A CNA2006800476420A CN200680047642A CN101330911A CN 101330911 A CN101330911 A CN 101330911A CN A2006800476420 A CNA2006800476420 A CN A2006800476420A CN 200680047642 A CN200680047642 A CN 200680047642A CN 101330911 A CN101330911 A CN 101330911A
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acid
hydroxy
polycarboxylate
ester
hydroxyl
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罗伊·J·于
沃金·J·范斯科特
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Abstract

A composition and method for producing a beneficial effect on nerves associated with at least one of a cosmetic, dermatological, and dental indication and another condition in a patient. The compositions comprise a hydroxy-polycarboxylate and are formulated for topical administration to a patient to produce a beneficial effect. The method comprises topically applying to the area of the patient in need of the beneficial effect a hydroxy-polycarboxylic acid ester in an amount effective to produce the beneficial effect.

Description

Hydroxyl-polycarboxylate: to the effect of nerve be used for skin and the purposes at mucocutaneous organs or position
The cross reference of related application
[0002] according to the 119th (e) money of the 35th piece of united states patent law of United States code (35U.S.C. § 119 (e)), authorize the U.S. Provisional Patent Application of submitting in 17 days October in 2005 that the application requires the 60/727th, the priority that No. the 60/759th, 525, No. 419 and the U.S. Provisional Patent Application submitted on January 17th, 2006.
Background of invention
[0003] the application relates to the purposes of the compositions that comprises hydroxyl-polycarboxylate (hydroxy-oligocarboxylicester), and it can be useful beauty treatment section disease (cosmetic conditions), odontopathy, dermatosis indication and other disease to neural effect (particularly relating to sensation and slight anesthesia character) wherein to alleviate or to improve that said composition is used for topical administration.
[0004] title is the United States Patent (USP) the 5th of " amphoteric composition of alpha-hydroxy acid and polymer form and therapeutic use thereof ", 091, No. 171, the preventative and therapeutic treatment of the amphoteric composition that adopts the polymer form that comprises alpha-hydroxy acid, α keto acid related compound or hydroxy acid has been described to alleviate beauty treatment section's disease and skin condition of illness.Title is No. the 5th, 547,988, the United States Patent (USP) of " alleviating the skin aging sign with glycolic, lactic acid or citric acid ", described 'alpha '-hydroxy acids and alleviated or improve purposes with inherent aging and external aging relevant skin, fingernail and hair variation sign.Title is No. the 5th, 385,938, the United States Patent (USP) of " method that adopts glycolic treatment wrinkle ", has described the purposes of glycolic topical therapeutic wrinkle.Title is the United States Patent (USP) the 5th of " phenyl α acyloxy alkanoic acid, derivant and therapeutic use thereof ", 258, No. 391, described the topical compositions that comprises phenyl α acyloxy alkanoic acid and derivant and strengthened fingernail, skin, lip and the cornified purposes of other mucosas.
[0005] title is No. the 5th, 665,776, the United States Patent (USP) of " the auxiliary enhancing local action of medicine ", has described the purposes that hydroxy carboxylic acid strengthens the therapeutical effect of cosmetics or pharmaceutical formulation.Title is the United States Patent (USP) the 5th of " the Alpha-hydroxy acid esters that is used for skin aging ", 686, No. 489, described the Alpha-hydroxy acid esters by stimulate the corium composition for example the biosynthesis of glycosaminoglycans, proteoglycan, collagen protein and elastin laminin increase the purposes that skin thickness and treatment comprise the aging relevant body wall variation of senile plaque, skin line, wrinkle, photoaging and aging skin.Title is No. the 5th, 889,054, the United States Patent (USP) of " method that adopts beta hydroxy acid treatment wrinkle ", has described the purposes that the compositions that comprises beta-hydroxy acid is used for topical therapeutic and aging relevant skin variation.Title is the United States Patent (USP) the 6th of " adopting hydroxy carboxylic acid or related compound to be used for the treatment of the method that aging with the inherence and external aging relevant skin changes ", 060, No. 512, described the compositions that comprises hydroxy carboxylic acid and be used for the purposes that aging with the inherence and the external aging relevant skin of topical therapeutic changes.Both titles are the United States Patent (USP) the 6th, 335, No. 023 and 6,740, No. 327 of " oligosaccharide glycuronic acid and topical use thereof ", have described the compositions that comprises the oligosaccharide glycuronic acid and have been used for topical therapeutic cosmetics symptom and dermopathic purposes.Title is the United States Patent (USP) the 6th of " method that adopts aging with the inherence and the external aging relevant skin of hydroxy carboxylic acid or related compound treatment to change ", 767, No. 924, described the compositions that in the both sexes system, comprises polyhydroxy acid and be used for topical therapeutic and the interior purposes that changes at the aging and external relevant skin that wears out.
[0006] Shang Mian patent does not have one to describe or hinted by the topical administration hydroxy polycarboxylic acid esters, such as hydroxydicarboxylic acid's ester or hydroxyl tricarboxylic ester effect or the effect to one or more nerves.
The invention summary
[0007] although hydroxyl-monocarboxylate does not act on nerve, but one aspect of the present invention is based on following discovery: with hydroxyl-polycarboxylate, preferred hydroxydicarboxylic acid's ester and more preferably the hydroxyl tricarboxylic ester be locally applied to mucosa, organ or position for example behind the lip, produce sensuously and slight anesthetic action and to be used for can be useful beauty treatment section or dentistry disease, skin indication or another kind of disease to neural effect wherein.
[0008] another aspect of the invention is to use to comprise and be used for topical to alleviate or to improve the method for compositions that comprises pain, pruritus, inflammation, erythema, dermatitis, eczema, psoriasis with nerve, skin or tooth system diseases associated, symptom or syndrome and be used for the hydroxyl-polycarboxylate of wound healing.Described hydroxyl-polycarboxylate, preferred hydroxydicarboxylic acid's ester and more preferably the hydroxyl tricarboxylic ester be the antioxidant neutral compound, comprise, for example diethyl tartrate., triethyl citrate, citric acid three propyl ester and citric acid three isopropyl esters.
[0009] of the present invention on the one hand be again to the patient with beauty treatment section disease, dermatosis indication and dentistry indication and another disease in the method for at least a relevant nerve generation beneficial effect, this method is included in the amount local application hydroxyl-polycarboxylate of the zone of needs of patients beneficial effect with effective generation beneficial effect.
[0010] be on the other hand again to the patient with beauty treatment section disease, dermatosis indication and dentistry indication and another disease at least a relevant nerve produce the method for beneficial effect, this method is included in the zone that the needs beneficial effect amount local application patient hydroxyl-polycarboxylate with effective generation beneficial effect, and wherein beneficial effect is at least a in sensation (sensuous) effect to nerve and the slight anesthetic action.
Definition
[0011] as used herein, singulative " ", " one " and " being somebody's turn to do " comprise plural object, unless context clearly indicates in addition.Mean one or more when for example relating to disease, disease, indication, symptom or syndrome and plant such disease, disease, indication, symptom or syndrome.
[0012] as used herein, term " beneficial effect " means the needed effect of benefit to planning, no matter be prevention or the inhibitory action of alleviating disease or the positive effect that needs, potentiation for example, happy typically sensation or consciousness or incentive action.
[0013] as used herein, " slight anesthetic action " is to such an extent as to still have the effect that to a certain degree sensation level of sensitivity has beneficial effect for nerve, the organ or tissue of wherein anesthesia.
[0014] as used herein, " sensorial effect " is for the excitation sense of gratification or the effect of the sense aspect of taking the lead, and level of sensitivity has beneficial effect.
[0015] as used herein, term " treatment ", " treatment " etc. refer to the beneficial effect that can be pharmacology, physiology, dermatological and/or sensorial effect that obtains requiring.Beneficial effect can be preventative preventing aspect disease or disease or the symptom wholly or in part, and/or partially or completely cure disease or disease and/or be attributable to disease or the side effect of disease and/or situation in sensation treatment in cause aspect the enhanced sensation it can is curative.Therefore, for example " treatment " or " treatment " be included in animal, preferably in mammal and more preferably any treatment of the disease in the people or disease, and comprise: (a) but be present in can easy ill disease or the disease patient's who is not still diagnosed strictly according to the facts disease or disease in prevention; (b) suppress disease or disease, for example suppress its development; (c) alleviate, alleviate or improve disease or disease, for example cause that disease or disease alleviate; All these, beneficial effect wherein is to need inhibitory action." treatment " or " treatment " also comprises existence or the enhancing that causes the sensation situation, and beneficial effect wherein is that the positive that needs strengthens sensation, consciousness or incentive action.
Detailed Description Of The Invention
[0016] the present invention is based on following discovery: when hydroxyl-polycarboxylate is used in the part, preferred hydroxydicarboxylic acid's ester or more preferably the hydroxyl tricarboxylic ester can be to mucocutaneous organs or for example lip, mouth, gums, nostril, nipple, cysthus, vagina, penis and anus sensigenous, consciousness and slightly anesthetic action of position for example during citric acid three propyl ester.The applicant also has been found that for example gluconic acid ethyl ester and ethyl lactate not sensigenous or slight anesthetic action under the same conditions of hydroxyl monocarboxylate by comparison.By hydroxyl-polycarboxylate, preferred hydroxydicarboxylic acid's ester the or more preferably sensation that produces of hydroxyl tricarboxylic ester and consciousness effect are different from fully by for example paralysis effect that causes of lignocaine and procaine of local anesthetic.The sensation, consciousness and the slight anesthetic action that are produced by hydroxyl of the present invention-polycarboxylate continue a few minutes usually to several hours.Nervine like this sensation or effect have many beauty treatments section, dentistry and Dermatology purposes.For example, will comprise hydroxyl-polycarboxylate, preferably comprise hydroxydicarboxylic acid's ester more preferably comprise the lipstick of hydroxyl tricarboxylic ester or lip gloss local application patient's lip after, sensation or consciousness can be provided.Can have useful application to neural sensation and some anesthetic action like this by what hydroxyl-polycarboxylate produced, for example alleviate the pruritus and the pain of lip, mouth, gums, nostril, nipple, cysthus, vagina, penis and anus, and be used for eczema, hemorrhoid, drying or with cysthus and the aging relevant disease of associated change of vagina.
[0017] one aspect of the invention is to the patient with beauty treatment section disease, dermatosis indication and dentistry indication and another disease at least a relevant nerve produce the method for beneficial effect, this method is included in the amount local application hydroxyl-polycarboxylate of the zone of needs of patients beneficial effect with effective generation beneficial effect.
[0018] be on the other hand to the patient with beauty treatment section disease, dermatosis indication and dentistry indication and another disease at least a relevant nerve produce the method for beneficial effect, method is included in the zone that the needs beneficial effect amount local application patient hydroxyl-polycarboxylate with effective generation beneficial effect, and wherein beneficial effect is at least a in the sensorial effect of nerve and the slight anesthetic action.
[0019] hydroxyl-polycarboxylate comprises at least a in diethyl malate, triethyl citrate, citric acid three propyl ester, citric acid three isopropyl esters, glucosaccharic acid diethylester (diethyl glucate) and the glucosaccharic acid dipropyl (dipropyl glucate) and their any combination.
[0020] another aspect of the present invention is hydroxyl-polycarboxylate, preferred hydroxydicarboxylic acid's ester or more preferably the hydroxyl tricarboxylic ester cure and the disease that alleviates the pain relevant, infection, inflammation and mucocutaneous organs or the position purposes of aphtha and toothache for example with wound healing.For oral disease, hydroxyl-polycarboxylate is formulated as solution or gel is used to wash mouthful, gargles or massage.
[0021] hydroxyl-polycarboxylate of the present invention is the antioxidant neutral compound.Of the present invention be antioxidant hydroxyl-polycarboxylate on the one hand again, be preferably hydroxydicarboxylic acid's ester or more preferably for the conduct of hydroxyl tricarboxylic ester by daylight, chemicals, laser treatment, free radical, electromagnetic radiation, the ionizing radiation for example mucocutaneous organs that causes of alpha ray, β ray, X-ray, gamma-rays or damage, insect bite or stimulation or the preventative nursing of other oxidative damages or the purposes of treatment of position, skin, hair or fingernail.
[0022] of the present invention is the application of hydroxyl-polycarboxylate at skin or mucocutaneous organs, position or damage location more on the one hand, and it is used for local prevention or treatment is selected from acne; Rosacea; Skin defective; Cellulitis (cellulite); Dermatosis; Dermatitis; Skin or nail infection; The dandruff; Xerosis cutis; Axersis; Eczema; Herpes; Ichthyosis (ichthyosis); Pseudofolliculitis barbae (pseudofolliculitis barbae); Pruritus; Psoriasis; Striae gravidarum (stretchmarks); Wart; Oral cavity or Gum disease; Zest, inflammatory, unsound, damage or unusual mucosa, skin, hair, fingernail, nostril, auditory meatus, anus or vaginal disorder; Unsmooth and the rough surface of skin, fingernail and hair; Reactivity, zest or telangiectasis skin; Be used for skin bleaching and blast and wound healing.
[0023] hydroxyl-polycarboxylate of the present invention is represented one group of organic compound that contains one or more hydroxyl and 2-10 carboxyl in molecule.Preferred hydroxyl-polycarboxylate contains one or more hydroxyl and 2-3 carboxyl in molecule.Most preferred hydroxyl-polycarboxylate contains one or more hydroxyl and 3 carboxyls in molecule, for example triethyl citrate and citric acid three propyl ester.
[0024] hydroxyl-polycarboxylate of the present invention can be described as follows.
[0025] (A) hydroxydicarboxylic acid's ester
[0026] hydroxydicarboxylic acid's ester can be divided into two groups, and one group is that monohydroxy dicarboxylic ester and another group are the dihydroxy dicarboxylic ester.
[0027] (1) monohydroxy dicarboxylic ester
The monohydroxy dicarboxylic ester contains a hydroxyl and two carboxyls.Universal architecture can be expressed as with following formula I:
R 1OOC C(OH)R 2 CHR 4 COOR 3 (I)
R wherein 1And R 3Be aralkyl or the aryl that has the alkyl of 1-19 carbon atom or have 6-19 carbon atom independently; R 2And R 4Independently for H, have the alkyl of 1-19 carbon atom or have the aralkyl or the aryl of 6-19 carbon atom; The H that is connected in any carbon atom can replace with I, F, Cl, Br or the alkoxyl with 1-19 carbon.That the monohydroxy dicarboxylic ester can be used as is saturated or undersaturated, stereoisomerism or non-stereomeric, straight shape or ramose chain or annular form present.
[0028] if the universal architecture of formula I can not comprise concrete monohydroxy dicarboxylic ester, chemical compound will be represented by its chemical name.
[0029] following is representational hydroxydicarboxylic acid's ester:
[0030] 2-hydroxyl fourth-1,4-two acid esters (malate): malic acid dimethyl ester, diethyl malate, malic acid dipropyl, malic acid diisopropyl ester, malic acid diamyl ester, malic acid dioctyl ester, malic acid diisooctyl ester and malic acid dibenzyl ester.
[0031] 2-hydroxy-2-methyl-Ding-1,4-two acid esters (citramalic acid ester): citramalic acid dimethyl ester, citramalic acid diethylester, citramalic acid dipropyl, citramalic acid diisopropyl ester, citramalic acid diamyl ester, citramalic acid dioctyl ester, citramalic acid diisooctyl ester and citramalic acid dibenzyl ester.
[0032] (2) dihydroxy dicarboxylic ester
[0033] the dihydroxy dicarboxylic ester contains two hydroxyls and two carboxyls.Universal architecture can be expressed as with Formula Il:
R 1OOC C(OH)R 2C(OH)R 4COOR 3 (II)
R wherein 1And R 3Be aralkyl or the aryl that has the alkyl of 1-19 carbon atom or have 6-19 carbon atom independently; R 2And R 3Independently for H, have the alkyl of 1-19 carbon atom or have the aralkyl or the aryl of 6-19 carbon atom; The H that is connected in any carbon atom can replace with I, F, Cl, Br or the alkoxyl with 1-19 carbon.That the dihydroxy dicarboxylic ester can be used as is saturated or undersaturated, stereoisomerism or non-stereomeric, straight shape or ramose chain or annular form present.
[0034] if the universal architecture of formula II can not comprise concrete dihydroxy dicarboxylic ester, chemical compound will be represented by its chemical name.
[0035] following is representational dihydroxy dicarboxylic ester:
[0036] 2,3-dihydroxy fourth-1,4-two acid esters (tartrate): dimethyl tartrate, diethyl tartrate., dipropyl tartrate, tartaric acid diisopropyl ester, diamyl tartrate, tartaric acid dioctyl ester, tartaric acid diisooctyl ester and tartaric acid dibenzyl ester.
[0037] (B) hydroxyl tricarboxylic ester
[0038] the hydroxyl tricarboxylic ester can be divided into three groups; (1) monohydroxy tricarboxylic ester, (2) dihydroxy tricarboxylic ester and (3) trihydroxy tricarboxylic ester.
[0039] (1) monohydroxy tricarboxylic ester
[0040] the monohydroxy tricarboxylic ester contains 1 hydroxyl and 3 carboxyls and can be divided into 4 groups, (a) citrate, (b) 1-Hydroxy-1,2,3-propanetricarboxylic acid. ester, (c) Homocitric acid ester and (d) homoisocitric acid ester.
[0041] (a) citrate
[0042] universal architecture of citrate can be expressed as following formula III:
R 1OOC CHR 2C(OH)(COOR 3)CHR 4 COOR 5 (III)
R wherein 1, R 3And R 5Be aralkyl or the aryl that has the alkyl of 1-19 carbon atom or have 6-19 carbon atom independently; R 2And R 4Independently for H, have the alkyl of 1-19 carbon atom or have the aralkyl or the aryl of 6-19 carbon atom; The H that is connected in any carbon atom can replace with I, F, Cl, Br or the alkoxyl with 1-19 carbon.That citrate can be used as is saturated or undersaturated, stereoisomerism or non-stereomeric, straight shape or ramose chain or annular form present.
[0043] if the universal architecture of formula III can not comprise concrete citrate, chemical compound will be represented by its chemical name.
[0044] following is representational citrate:
[0045] 3-hydroxyl-3-carboxyl penta-1,5-two acid esters (citrate): trimethyl citrate, triethyl citrate, citric acid three propyl ester, citric acid triisopropyl ester, tripentyl citrates, trioctyl lemon acid, citric acid three isooctyl acrylate, citric acid tribenzyl ester and citric acid three cigarette esters (trinicotinyl citrate).
[0046] 2-n-hexadecyl-3-hydroxyl-3-carboxyl penta-1,5-two acid esters (armillaria Matsutake acid esters (agaricate esters), n-hexadecyl citrate): agaric acid trimethyl, agaric acid triethyl, agaric acid three propyl ester, agaric acid triisopropyl ester, agaric acid triamyl, agaric acid three monooctyl esters, agaric acid three isooctyl acrylate, agaric acid tribenzyl ester and agaric acid three cigarette esters.
[0047] (b) 1-Hydroxy-1,2,3-propanetricarboxylic acid. ester
[0048] universal architecture of 1-Hydroxy-1,2,3-propanetricarboxylic acid. ester can be expressed as with following formula IV:
R 1OOC C(OH)R 2 CR 4(COOR 3)CHR 6 COOR 3 (IV)
R wherein 1, R 3And R 5Be aralkyl or the aryl that has the alkyl of 1-19 carbon atom or have 6-19 carbon atom independently; R 2, R 4And R 6Independently for H, have the alkyl of 1-19 carbon atom or have the aralkyl or the aryl of 6-19 carbon atom; The H that is connected in any carbon atom can replace with I, F, Cl, Br or the alkoxyl with 1-19 carbon.That the 1-Hydroxy-1,2,3-propanetricarboxylic acid. ester can be used as is saturated or undersaturated, stereoisomerism or non-stereomeric, straight shape or ramose chain or annular form present.
[0049] if the universal architecture of formula IV can not comprise concrete 1-Hydroxy-1,2,3-propanetricarboxylic acid. ester, chemical compound will be represented by its chemical name.
[0050] following is representational 1-Hydroxy-1,2,3-propanetricarboxylic acid. ester:
[0051] 2-hydroxyl-3-carboxyl penta-1,5-two acid esters (1-Hydroxy-1,2,3-propanetricarboxylic acid. ester): 1-Hydroxy-1,2,3-propanetricarboxylic acid. trimethyl, 1-Hydroxy-1,2,3-propanetricarboxylic acid. triethyl, 1-Hydroxy-1,2,3-propanetricarboxylic acid. three propyl ester, 1-Hydroxy-1,2,3-propanetricarboxylic acid. triisopropyl ester, 1-Hydroxy-1,2,3-propanetricarboxylic acid. triamyl, 1-Hydroxy-1,2,3-propanetricarboxylic acid. three monooctyl esters, 1-Hydroxy-1,2,3-propanetricarboxylic acid. three isooctyl acrylate, 1-Hydroxy-1,2,3-propanetricarboxylic acid. tribenzyl ester and 1-Hydroxy-1,2,3-propanetricarboxylic acid. three cigarette esters.
[0052] (c) Homocitric acid ester
The universal architecture of Homocitric acid ester can be expressed as with following formula V:
R 1OOC CHR 2C(OH)(COOR 3)CHR 4 CHR 6 COOR 5 (V)
R wherein 1, R 3And R 5Be aralkyl or the aryl that has the alkyl of 1-19 carbon atom or have 6-19 carbon atom independently; R 2, R 4And R 6Independently for H, have the alkyl of 1-19 carbon atom or have the aralkyl or the aryl of 6-19 carbon atom; The H that is connected in any carbon atom can replace with I, F, Cl, Br or the alkoxyl with 1-19 carbon.That the Homocitric acid ester can be used as is saturated or undersaturated, stereoisomerism or non-stereomeric, straight shape or ramose chain or annular form present.
[0053] if the universal architecture of formula V can not comprise concrete Homocitric acid ester, chemical compound will be represented by its chemical name.
[0054] following is representational Homocitric acid ester:
[0055] 3-hydroxyl-3-carboxyl oneself-1,6-two acid esters (Homocitric acid ester): Homocitric acid trimethyl, Homocitric acid triethyl, Homocitric acid three propyl ester, Homocitric acid triisopropyl ester, Homocitric acid triamyl, Homocitric acid three monooctyl esters, Homocitric acid three isooctyl acrylate, Homocitric acid tribenzyl ester and Homocitric acid three cigarette esters.
[0056] (d) homoisocitric acid ester
[0057] universal architecture of homoisocitric acid ester can be expressed as with following formula VI:
R 1OOC C(OH)R 2CR 4(COOR 3)CHR 6 CHR 7COOR 5 (VI)
R wherein 1, R 3And R 5Be aralkyl or the aryl that has the alkyl of 1-19 carbon atom or have 6-19 carbon atom independently; R 2, R 4, R 6And R 7Independently for H, have the alkyl of 1-19 carbon atom or have the aralkyl or the aryl of 6-19 carbon atom; The H that is connected in any carbon atom can replace with I, F, Cl, Br or the alkoxyl with 1-19 carbon.That the homoisocitric acid ester can be used as is saturated or undersaturated, stereoisomerism or non-stereomeric, straight shape or ramose chain or annular form present.
[0058] if the universal architecture of formula VI can not comprise concrete homoisocitric acid ester, chemical compound will be represented by its chemical name.
[0059] following is representational homoisocitric acid ester:
[0060] 2-hydroxyl-3-carboxyl oneself-1,6-two acid esters (homoisocitric acid ester): homoisocitric acid trimethyl, homoisocitric acid triethyl, homoisocitric acid three propyl ester, homoisocitric acid triisopropyl ester, homoisocitric acid triamyl, homoisocitric acid three monooctyl esters, homoisocitric acid three isooctyl acrylate, homoisocitric acid tribenzyl ester and homoisocitric acid three cigarette esters.
[0061] (2) dihydroxy tricarboxylic ester
[0062] the dihydroxy tricarboxylic ester contains 2 hydroxyls and 3 carboxyls.The dihydroxy tricarboxylic ester that has 5 subgroups: (a) hydroxycitric acid ester; (b) hydroxyl 1-Hydroxy-1,2,3-propanetricarboxylic acid. ester; (c) hydroxyl Homocitric acid ester; (d) hydroxyl homoisocitric acid ester; (e) 4,5-dihydroxy-3-carboxyl hexane-1,6-two acid esters.
[0063] (a) hydroxycitric acid ester
[0064] universal architecture can be expressed as with following formula VII:
R 1OOC C(OH)R 2C(OH)(COOR 3)CHR 4 COOR 5 (VII)
R wherein 1, R 3And R 5Be aralkyl or the aryl that has the alkyl of 1-19 carbon atom or have 6-19 carbon atom independently; R 2And R 4Independently for H, have the alkyl of 1-19 carbon atom or have the aralkyl or the aryl of 6-19 carbon atom; The H that is connected in any carbon atom can replace with I, F, Cl, Br or the alkoxyl with 1-19 carbon.That the hydroxycitric acid ester can be used as is saturated or undersaturated, stereoisomerism or non-stereomeric, straight shape or ramose chain or annular form present.
[0065] if the universal architecture of formula VII can not comprise concrete hydroxycitric acid ester, chemical compound will be represented by its chemical name.
[0066] following is representational hydroxycitric acid ester:
[0067] 2,3-dihydroxy-3-carboxyl penta-1,5-two acid esters (hydroxycitric acid ester): hydroxycitric acid trimethyl, hydroxycitric acid triethyl, hydroxycitric acid three propyl ester, hydroxycitric acid triisopropyl ester, hydroxycitric acid triamyl, hydroxycitric acid three monooctyl esters, hydroxycitric acid three isooctyl acrylate, hydroxycitric acid tribenzyl ester and hydroxycitric acid three cigarette esters.
[0068] 2-n-hexadecyl-2,3-dihydroxy-3-carboxyl penta-1,5-two acid esters and 4-n-hexadecyl-2,3-dihydroxy-3-carboxyl penta-1,5-two acid esters (hydroxyl armillaria Matsutake acid esters, n-hexadecyl hydroxycitric acid ester): hydroxyl agaric acid trimethyl, hydroxyl agaric acid triethyl, hydroxyl agaric acid three propyl ester, hydroxyl agaric acid triisopropyl ester, hydroxyl agaric acid triamyl, hydroxyl agaric acid three monooctyl esters, hydroxyl agaric acid three isooctyl acrylate, hydroxyl agaric acid tribenzyl ester and hydroxyl agaric acid three cigarette esters.
[0069] (b) hydroxyl 1-Hydroxy-1,2,3-propanetricarboxylic acid. ester
[0070] universal architecture can be expressed as with following formula VIII:
R 1OOC C(OH)R 2CR 4(COOR 3)C(OH)R 6COOR 5 (VIII)
R wherein 1, R 3And R 5Be aralkyl or the aryl that has the alkyl of 1-19 carbon atom or have 6-19 carbon atom independently; R 2, R 4And R 6Independently for H, have the alkyl of 1-19 carbon atom or have the aralkyl or the aryl of 6-19 carbon atom; The H that is connected in any carbon atom can replace with I, F, Cl, Br or the alkoxyl with 1-19 carbon.That hydroxyl 1-Hydroxy-1,2,3-propanetricarboxylic acid. ester can be used as is saturated or undersaturated, stereoisomerism or non-stereomeric, straight shape or ramose chain or annular form present.
[0071] if the universal architecture of formula VIII can not comprise concrete hydroxyl 1-Hydroxy-1,2,3-propanetricarboxylic acid. ester, chemical compound will be represented by its chemical name.
[0072] following is representational hydroxyl 1-Hydroxy-1,2,3-propanetricarboxylic acid. ester:
[0073] 2,4-dihydroxy-3-carboxyl penta-1,5-two acid esters (hydroxyl 1-Hydroxy-1,2,3-propanetricarboxylic acid. ester): hydroxyl 1-Hydroxy-1,2,3-propanetricarboxylic acid. trimethyl, hydroxyl 1-Hydroxy-1,2,3-propanetricarboxylic acid. triethyl, hydroxyl 1-Hydroxy-1,2,3-propanetricarboxylic acid. three propyl ester, hydroxyl 1-Hydroxy-1,2,3-propanetricarboxylic acid. triisopropyl ester, hydroxyl 1-Hydroxy-1,2,3-propanetricarboxylic acid. triamyl, hydroxyl 1-Hydroxy-1,2,3-propanetricarboxylic acid. three monooctyl esters, hydroxyl 1-Hydroxy-1,2,3-propanetricarboxylic acid. three isooctyl acrylate, hydroxyl 1-Hydroxy-1,2,3-propanetricarboxylic acid. tribenzyl ester and hydroxyl 1-Hydroxy-1,2,3-propanetricarboxylic acid. three cigarette esters.
[0074] (c) hydroxyl Homocitric acid ester
[0075] because there are 3 kinds of universal architectures that can be expressed as with following formula IX, X and XI in the position of second hydroxyl:
R 1OOC C(OH)R 2C(OH)(COOR 3)CHR 4 CHR 6 COOR 5 (IX)
R 1OOC CHR 2C(OH)(COOR 3)C(OH)R 4 CHR 6 COOR 5 (X)
R 1OOC CHR 2C(OH)(COOR 3)CHR 4 C(OH)R 6 COOR 5 (XI)
Wherein in each of formula IX, X and XI, R 1, R 3And R 5Be aralkyl or the aryl that has the alkyl of 1-19 carbon atom or have 6-19 carbon atom independently; R 2, R 4And R 6Independently for H, have the alkyl of 1-19 carbon atom or have the aralkyl or the aryl of 6-19 carbon atom; The H that is connected in any carbon atom can replace with I, F, Cl, Br or the alkoxyl with 1-19 carbon.That hydroxyl Homocitric acid ester can be used as is saturated or undersaturated, stereoisomerism or non-stereomeric, straight shape or ramose chain or annular form present.
[0076] if the universal architecture of formula IX, X or XI can not comprise concrete hydroxyl Homocitric acid ester, chemical compound will be represented by its chemical name.
[0077] following is representational hydroxyl Homocitric acid ester:
[0078] 2,3-dihydroxy-3-carboxyl own-1,6-two acid esters, 3,4-dihydroxy-3-carboxyl own-1,6-two acid esters and 3,5-dihydroxy-3-carboxyl oneself-1,6-two acid esters (hydroxyl Homocitric acid ester): hydroxyl Homocitric acid trimethyl, hydroxyl Homocitric acid triethyl, hydroxyl Homocitric acid three propyl ester, hydroxyl Homocitric acid triisopropyl ester, hydroxyl Homocitric acid triamyl, hydroxyl Homocitric acid three monooctyl esters, hydroxyl Homocitric acid three isooctyl acrylate, hydroxyl Homocitric acid tribenzyl ester and hydroxyl Homocitric acid three cigarette esters.
[0079] (d) hydroxyl homoisocitric acid ester
[0080] because there are 2 kinds of universal architectures that can be expressed as with following formula XII and XIII in the position of second hydroxyl:
R 1OOC C(OH)R 2CR 4(COOR 3)C(OH)R 6 CHR 7 COOR 5 (XII)
R 1OOC C(OH)R 2CR 4(COOR 3)CHR 6C(OH)R 7COOR 5 (XIII)
Wherein in each of formula XII and XIII, R 1, R 3And R 5Be aralkyl or the aryl that has the alkyl of 1-19 carbon atom or have 6-19 carbon atom independently; R 2, R 4, R 6And R 7Independently for H, have the alkyl of 1-19 carbon atom or have the aralkyl or the aryl of 6-19 carbon atom; The H that is connected in any carbon atom can replace with I, F, Cl, Br or the alkoxyl with 1-19 carbon.That hydroxyl homoisocitric acid ester can be used as is saturated or undersaturated, stereoisomerism or non-stereomeric, straight shape or ramose chain or annular form present.
[0081] if the universal architecture of formula XII or XIII can not comprise concrete hydroxyl homoisocitric acid ester, chemical compound will be represented by its chemical name.
[0082] following is representational hydroxyl homoisocitric acid ester:
[0083] 2,4-dihydroxy-3-carboxyl own-1,6-two acid esters and 2,5-dihydroxy-3-carboxyl oneself-1,6-two acid esters (hydroxyl homoisocitric acid ester): hydroxyl homoisocitric acid trimethyl, hydroxyl homoisocitric acid triethyl, hydroxyl homoisocitric acid three propyl ester, hydroxyl homoisocitric acid triisopropyl ester, hydroxyl homoisocitric acid triamyl, hydroxyl homoisocitric acid three monooctyl esters, hydroxyl homoisocitric acid three isooctyl acrylate, hydroxyl homoisocitric acid tribenzyl ester and hydroxyl homoisocitric acid three cigarette esters.
[0084] (e) 4,5-dihydroxy-3-carboxyl oneself-1,6-two acid esters
[0085] universal architecture can be expressed as with following formula XIV:
R 1OOC CHR 2CR 4(COOR 3)C(OH)R 6 C(OH)R 7COOR 5 (XIV)
R wherein 1, R 3And R 5Be aralkyl or the aryl that has the alkyl of 1-19 carbon atom or have 6-19 carbon atom independently; R 2, R 4, R 6And R 7Independently for H, have the alkyl of 1-19 carbon atom or have the aralkyl or the aryl of 6-19 carbon atom; The H that is connected in any carbon atom can replace with I, F, Cl, Br or the alkoxyl with 1-19 carbon.4,5-dihydroxy-3-carboxyl oneself-1, that 6-two acid esters can be used as is saturated or undersaturated, stereoisomerism or non-stereomeric, straight shape or ramose chain or annular form present.
[0086] concrete 4 if the universal architecture of formula XIV can not comprise, 5-dihydroxy-3-carboxyl oneself-1,6-two acid esters, chemical compound will be represented by its chemical name.
[0087] following be representational 4, and 5-dihydroxy-3-carboxyl is own-1,6-two acid esters: 4,5-dihydroxy-3-carboxyl own-1,6-diacid trimethyl, 4,5-dihydroxy-3-carboxyl oneself-1,6-diacid triethyl, 4,5-dihydroxy-3-carboxyl own-1,6-diacid three propyl ester, 4,5-dihydroxy-3-carboxyl oneself-1,6-diacid triisopropyl ester, 4,5-dihydroxy-3-carboxyl own-1,6-diacid triamyl, 4,5-dihydroxy-3-carboxyl oneself-1,6-diacid three monooctyl esters, 4,5-dihydroxy-3-carboxyl own-1,6-diacid three isooctyl acrylate, 4,5-dihydroxy-3-carboxyl oneself-1,6-diacid tribenzyl ester and 4,5-dihydroxy-3-carboxyl oneself-1,6-diacid three cigarette esters.
[0088] (3) trihydroxy tricarboxylic ester
[0089] the trihydroxy tricarboxylic ester contains 3 hydroxyls and 3 carboxyls.The trihydroxy tricarboxylic ester that has 3 subgroups: (a) dihydroxy citrate, (b) dihydroxy Homocitric acid ester and (c) dihydroxy homoisocitric acid ester.
[0090] (a) dihydroxy citrate
[0091] universal architecture can be expressed as with following formula XV:
R 1OOC C(OH)R 2C(OH)(COOR 3)C(OH)R 4 COOR 5 (XV)
R wherein 1, R 3And R 5Be aralkyl or the aryl that has the alkyl of 1-19 carbon atom or have 6-19 carbon atom independently; R 2And R 4Independently for H, have the alkyl of 1-19 carbon atom or have the aralkyl or the aryl of 6-19 carbon atom; The H that is connected in any carbon atom can replace with I, F, Cl, Br or the alkoxyl with 1-19 carbon.That the dihydroxy citrate can be used as is saturated or undersaturated, stereoisomerism or non-stereomeric, straight shape or ramose chain or annular form present.
[0092] if the universal architecture of formula XV can not comprise concrete dihydroxy citrate, chemical compound will be represented by its chemical name.
[0093] following is representational dihydroxy citrate: 2,3,4-trihydroxy-3-carboxyl penta-1,5-two acid esters (dihydroxy citrate): dihydroxy trimethyl citrate, dihydroxy triethyl citrate, dihydroxy citric acid three propyl ester, dihydroxy citric acid triisopropyl ester, dihydroxy tripentyl citrates, dihydroxy trioctyl lemon acid, dihydroxy citric acid three isooctyl acrylate, dihydroxy citric acid tribenzyl ester and dihydroxy citric acid three cigarette esters.
[0094] (b) dihydroxy Homocitric acid ester
[0095] because there are 3 kinds of universal architectures that can be expressed as following formula XVI, XVII and XVIII in the position of second and the 3rd hydroxyl:
R 1OOC C(OH)R 2C(OH)(COOR 3)C(OH)R 4 CHR 6 COOR 5 (XVI)
R 1OOC C(OH)R 2C(OH)(COOR 3)CHR 4C(OH)R 6 COOR 5 (XVII)
R 1OOC CHR 2C(OH)(COOR 3)C(OH)R 4 C(OH)R 6 COOR 5 (XVIII)
Wherein in each of formula XVI, XVII and XVIII, R 1, R 3And R 5Be aralkyl or the aryl that has the alkyl of 1-19 carbon atom or have 6-19 carbon atom independently; R 2, R 4And R 6Independently for H, have the alkyl of 1-19 carbon atom or have the aralkyl or the aryl of 6-19 carbon atom; The H that is connected in any carbon atom can replace with I, F, Cl, Br or the alkoxyl with 1-19 carbon.That dihydroxy Homocitric acid ester can be used as is saturated or undersaturated, stereoisomerism or non-stereomeric, straight shape or ramose chain or annular form present.
[0096] if the universal architecture of formula XVI, XVII or XVIII can not comprise concrete dihydroxy Homocitric acid ester, chemical compound will be represented by its chemical name.
[0097] following is representational dihydroxy Homocitric acid ester:
[0098] 2,3,4-trihydroxy-3-carboxyl own-1,6-two acid esters, 2,3,5-trihydroxy-3-carboxyl own-1,6-two acid esters and 3,4,5-trihydroxy-3-carboxyl oneself-1,6-two acid esters (dihydroxy Homocitric acid ester): dihydroxy Homocitric acid trimethyl, dihydroxy Homocitric acid triethyl, dihydroxy Homocitric acid three propyl ester, dihydroxy Homocitric acid triisopropyl ester, dihydroxy Homocitric acid triamyl, dihydroxy Homocitric acid three monooctyl esters, dihydroxy Homocitric acid three isooctyl acrylate, dihydroxy Homocitric acid tribenzyl ester and dihydroxy Homocitric acid three cigarette esters.
[0099] (c) dihydroxy homoisocitric acid ester
[00100] universal architecture can be expressed as with following formula XIX:
R 1OOC C(OH)R 2 CR 4(COOR 3)C(OH)R 6 C(OH)R 7 COOR 5 (XIX)
R wherein 1, R 3And R 5Be aralkyl or the aryl that has the alkyl of 1-19 carbon atom or have 6-19 carbon atom independently; R 2, R 4, R 6And R 7Independently for H, have the alkyl of 1-19 carbon atom or have the aralkyl or the aryl of 6-19 carbon atom; The H that is connected in any carbon atom can replace with I, F, Cl, Br or the alkoxyl with 1-19 carbon.That dihydroxy homoisocitric acid ester can be used as is saturated or undersaturated, stereoisomerism or non-stereomeric, straight shape or ramose chain or annular form present.
[00101] if universal architecture formula XIX can not comprise concrete dihydroxy homoisocitric acid ester, chemical compound will be represented by its chemical name.
[00102] following is representational dihydroxy homoisocitric acid ester: 2,4,5-trihydroxy-3-carboxyl oneself-1,6-two acid esters (dihydroxy homoisocitric acid ester): dihydroxy homoisocitric acid trimethyl, dihydroxy homoisocitric acid triethyl, dihydroxy homoisocitric acid three propyl ester, dihydroxy homoisocitric acid triisopropyl ester, dihydroxy homoisocitric acid triamyl, dihydroxy homoisocitric acid three monooctyl esters, dihydroxy homoisocitric acid three isooctyl acrylate, dihydroxy homoisocitric acid tribenzyl ester and dihydroxy homoisocitric acid three cigarette esters.
[00103] common, the applicant has been found that the sensation that produced by the hydroxyl tricarboxylic ester and consciousness effect are more much better than and the persistent period is longer than the described effect that is produced by hydroxydicarboxylic acid's ester.In the hydroxyl tricarboxylic ester of identical family, the applicant has been found that also the sensation and the consciousness effect that are produced by the ester than long-chain are longer than the much better than and persistent period that is produced described effect by the ester than short chain.For example, citric acid three propyl ester produce sensation and consciousness effect much better than and that the persistent period is longer than trimethyl citrate.
[00104] also cosmetics, medicinal and other topical drugs can be joined and be used for collaborative or potentiation in the present composition.Topical drug comprises, for example (is not limited to) hydroxy acid, keto acid and related compound; Phenyl α acyloxy alkanoic acid and derivant, N-acyl group-aldose amine (aldosamines), N-acylamino acid and relevant N-acyl compounds; Local analgesia medicine and anesthetics; Anti-acne drug; Antimicrobial drug; Anti-yeast medicine; Antifungal agent; Antiviral agents; Anti-infective; The anti-dandruff medicine; Anti-dermatitis medicine; Antieczematic; Antihistaminic; The antipruritic medicine; Bendectin; Motion sickness drug; Anti-inflammatory agent; Anti-hyperkeratosis medicine; Antiperspirant; Antipsoriatic; Anti-rosacea medicine; Seborrhea; Hair conditioner and hair therapy medicine; Defying age and crease-resistant medicine; Antianxiety drugs; Anticonvulsant; Antidepressants; Sun-proof and opacifier; Skin lightening agent; Depigmenting agent; Astringency; Cleaning agent; Clavus; Callus and remove the wart agent; Skin plentiful (plumping) agent; (volumizing) agent of preserving moisture that skin is plentiful; The Firm agent; Matrix metalloproteinase (MMP) inhibitor; The local cardiovascular drug of using; Wound-healing agent; Gingival or mouth care medicine; Aminoacid; The peptide class; Dipeptides; Tripeptides; Glutathion and derivant thereof; Oligopeptide; Polypeptide; Saccharide; Aminosaccharide; Vitamin; Corticosteroid; Tanning agent; Hormone and retinoid.
[0101] logical method preparation
[0102] can hydroxyl-polycarboxylate of the present invention will be contained, preferred hydroxydicarboxylic acid's ester, more preferably the compositions of hydroxyl tricarboxylic ester is formulated as solution, gel, lotion, cream, ointment, shampoo, spray, rod, pad, powder, face shield (masque), mouthwass or collutory, vagina gel or vagina preparation, or to being used for mucocutaneous position etc., such as acceptable other forms of oral mucosa, lip, nostril, cysthus, vagina, penis and nipple.
[0103] for the preparation liquid composite, with at least a hydroxyl-polycarboxylate, preferred hydroxydicarboxylic acid's ester and more preferably the hydroxyl tricarboxylic ester be dissolved in water, ethanol, propylene glycol, butanediol and/or other local acceptable vehicle.It is about 100% that the concentration of hydroxyl-polycarboxylate can be about 0.1%-of total composition weight, and about 1%-that preferred concentration is total composition weight is about 40%, and preferred concentration is about 2%-about 20% of total composition weight.
[0104] in order to prepare the topical compositions of lotion, cream or ointment form, liquid form hydroxyl-polycarboxylate directly can be mixed with the substrate that requires, perhaps can at first be dissolved in ethanol, propylene glycol and/or other solvents, and make so the solution that obtains mixes with substrate or pharmaceutically acceptable vehicle with preparation lotion, cream or ointment.Concentration is identical with above requirement.
[0105] also topical compositions of the present invention can be formulated as the gel form.By in the solution that contains hydroxyl-polycarboxylate of the present invention, adding the gelling forming agent, such as chitosan, methylcellulose, ethyl cellulose, polyvinyl alcohol, polyquaternary amine ion, hydroxyethyl-cellulose, hydroxypropyl cellulose, hydroxypropyl emthylcellulose, carbomer or ammonification glycyrrhetate preparation typical gels agent compositions.The preferred concentration of gellant can be about 0.2%-about 2% of total composition weight.
[0106] in order to prepare the part that is used for collaborative or potentiation with associating compositions, cosmetics, medicinal or other Topically active medicines are added in the described preparation by dissolving or mixing, combine with above any compositions.
[0107] those skilled in the art can be easy to other form compositionss that fusion, preparation or preparation are used to transmit The compounds of this invention according to the disclosure.
[0108] contain hydroxyl-polycarboxylate, the compositions that preferably contains hydroxydicarboxylic acid's ester and more preferably contain the hydroxyl tricarboxylic ester can locally apply to mucocutaneous organs or the position is used for sensigenous and consciousness effect.Mucocutaneous organs or position comprise lip, mouth, gums, nostril, nipple, cysthus, vagina, penis and anus.Such as noted above, sensation that is produced by hydroxyl-polycarboxylate and consciousness effect are different from fully by for example numbness effect that causes of lignocaine and procaine of local anesthetic.The sensation and the consciousness effect that are produced by hydroxyl-polycarboxylate continue a few minutes usually to several hours.For example, will comprise hydroxydicarboxylic acid's ester preferably comprise the lipstick of hydroxyl tricarboxylic ester or lip that lip gloss is locally applied to patient after, sensation or consciousness can be provided.For example, cream or the ointment that contains 10% triethyl citrate, citric acid three propyl ester or citric acid three isopropyl esters can be locally applied to lip.After 1-2 minute, lip will experience sensation and consciousness happiness, follow very slight anesthetic action, and the people feel that lip blow-up on volume is plentiful.Such sensation continues about 10 minutes to 2 hours usually.
[0109] be useful to neural effect to many other beauty treatment sections, dentistry and dermatosis indication like this, for example alleviate the pruritus and the pain of lip, mouth, gums, nostril, nipple, cysthus, vagina, penis and anus, and be useful the disease relevant with the aging relevant variation of eczema, hemorrhoid, drying or cysthus and vagina.
[0110] contain hydroxyl-polycarboxylate, preferred hydroxydicarboxylic acid's ester and more preferably the compositions of hydroxyl tricarboxylic ester also can locally apply to mucosa or cutaneous lesion.For example, but contain and the cream of 10% citric acid, three propyl ester or citric acid three isopropyl esters or ointment every day be locally applied to eczema or psoriasis damage 4-16 week 2 times.The pruritus relevant with eczema or psoriasis disappears in a few minutes after local application usually.
[0111] another aspect of the present invention is hydroxyl-polycarboxylate, preferred hydroxydicarboxylic acid's ester, the disease that alleviates the pain relevant with wound healing, infection and/or inflammation and mucocutaneous organs or position with more preferably hydroxyl tricarboxylic ester be the purposes of oral ulcer and toothache for example.For oral disease, hydroxyl-polycarboxylate is formulated as solution or gel form is used for the oral cavity and cleans, gargle or massage.
[0112] according to the anti-oxidant properties of hydroxyl-polycarboxylate, another aspect of the present invention is their application, and be preferably antioxidant hydroxydicarboxylic acid ester or more preferably for antioxidant hydroxyl tricarboxylic ester as to by daylight, chemicals, laser treatment, free radical, electromagnetic radiation, the ionizing radiation for example mucocutaneous organs that causes of alpha ray, β ray, X-ray, gamma-rays or damage, insect bite or stimulation or the preventative nursing of other oxidative damages or the purposes of treatment of position, skin, hair or fingernail.
[0113] now the preferred embodiments of the invention is described in detail according to following embodiment concrete, indefiniteness.
[0114] embodiment 1
[0115] glycolic ethyl ester 10g is mixed with the ointment of 50 parts of 90g confession mineral tallows, 40 parts in mineral oil and 10 parts of preparations of cera alba.Therefore the compositions of preparation contains 10% glycolic ethyl ester in the hydrophobic ointment (can not wash ointment) of unavailable water washing.
[0116] 10% glycolic ethyl ester ointment more than the local application on the lip of the male subject at an age 73.In next not sensation or consciousness in 30 minutes.This as a result the signify hydroxy monocarboxylate nerve at mucocutaneous position is not produced any effect.
[0117] embodiment 2
[0118] L-ethyl lactate 10g is mixed with the ointment of 50 parts of 90g confession mineral tallows, 40 parts in mineral oil and 10 parts of preparations of cera alba.Therefore the compositions of preparation contains the 10%L-ethyl lactate can not washing in the ointment.
The above 10%L-ethyl lactate of local application ointment on the lip of the male subject at an age 73.In next not sensation or consciousness in 30 minutes.This result shows that different hydroxyl monocarboxylates does not produce any effect to the nerve at mucocutaneous position.
[0119] embodiment 3
DL-diethyl malate 10g is mixed with the ointment of 50 parts of 90g confession mineral tallows, 40 parts in mineral oil and 10 parts of preparations of cera alba.Therefore the compositions of preparation contains the 10%DL-diethyl malate can not washing in the ointment.
[0120] the above 10%DL-diethyl malate of local application ointment on the lip of the male subject at an age 73.After 1-2 minute, lip has experienced lasting about 10-about 20 minutes sensation and sense of fullness.Effect signify hydroxy dicarboxylic ester to nervus labialis can provide useful effect like this, and it is the representative to various beauty treatment section's diseases and other beneficial effects of dermatosis indication.
[0121] embodiment 4
[0122] D-diethyl tartrate. 10g is mixed with the ointment of 50 parts of 90g confession mineral tallows, 40 parts in mineral oil and 10 parts of preparations of cera alba.Therefore the compositions of preparation contains the 10%D-diethyl tartrate. can not washing in the ointment.
[0123] the above 10%D-diethyl tartrate. of local application ointment on the lip of the male subject at an age 73.After 1-2 minute, lip has experienced lasting about 10-about 20 minutes slight sensation and sense of fullness.Effect to nervus labialis shows that the dihydroxy dicarboxylic ester can provide useful effect like this, and it is the representative to various beauty treatment section's diseases and other beneficial effects of dermatosis indication.
[0124] embodiment 5
[0125] L-diethyl tartrate. 10g is mixed with the ointment of 50 parts of 90g confession mineral tallows, 40 parts in mineral oil and 10 parts of preparations of cera alba.Therefore the compositions of preparation contains at the 10%L-diethyl tartrate. that can not wash in the ointment.
The above 10%L-diethyl tartrate. of local application ointment on the lip of the male subject at an age 73.After 1-2 minute, lip has experienced lasting about 10-about 20 minutes slight sensation and sense of fullness.Effect to nervus labialis shows that the dihydroxy dicarboxylic ester can provide useful effect like this, and it is the representative to various beauty treatment section's diseases and other beneficial effects of dermatosis indication.
[0126] embodiment 6
[0127] triethyl citrate 10g and propylene glycol 10ml are mixed with hydrophilic ointment or oil in water emulsion 80g.Therefore the compositions of preparation contains 10% triethyl citrate in water-soluble oil in water emulsion.
[0128] 10% triethyl citrate cream more than the local application on the lip of the male subject at an age 73.After 1-2 minute, lip has experienced lasting about 20-about 30 minutes sensation and sense of fullness.Effect to nervus labialis shows that the monohydroxy tricarboxylic ester can provide useful effect like this, and it is the representative to various beauty treatment section's diseases and other beneficial effects of dermatosis indication.
[0129] embodiment 7
[0130] triethyl citrate 10g is mixed with the ointment of 50 parts of 90g confession mineral tallows, 40 parts in mineral oil and 10 parts of preparations of cera alba.Therefore the compositions of preparation contains 10% triethyl citrate can not washing in the ointment.
[0131] 7 volunteer, 4 male and 3 women, 10% triethyl citrate cream more than the local application on its lip.After 1-2 minute, lip has experienced lasting about 20-about 30 minutes sensation and sense of fullness.Like this effect of nervus labialis is shown, in the preparation different with embodiment 6 and the monohydroxy tricarboxylic ester that uses by several experimenters useful effect can be provided, it is the representative to various beauty treatment section's diseases and other beneficial effects of dermatosis indication.
[0132] embodiment 8
[0133] triethyl citrate 10g is mixed with the ointment of 50 parts of 90g confession mineral tallows, 40 parts in mineral oil and 10 parts of preparations of cera alba.Therefore the compositions of preparation contains 10% triethyl citrate can not washing in the ointment.
[0134], suffers from allergic eczema and follow above 10% triethyl citrate of local application on male patient's the right rear leg pruritus skin of serious skin pruritus an age 73.After a few minutes, pruritus stops and keeping not having pruritus at 4 hours subsequently skin.This result shows that the monohydroxy tricarboxylic ester can provide useful antipruritic effect, and it is the representative to various beauty treatment section's diseases and other beneficial effects of dermatosis indication.
[0135] embodiment 9
[0136] triethyl citrate 10g is mixed with the ointment of 50 parts of 90g confession mineral tallows, 40 parts in mineral oil and 10 parts of preparations of cera alba.Therefore the compositions of preparation contains 10% triethyl citrate can not washing in the ointment.
[0137] 10% trimethyl citrate ointment more than the local application on the lip of the male subject at an age 73.After 1-2 minute, lip has experienced very slight sensation and sense of fullness.Effect to nervus labialis shows that another kind of monohydroxy tricarboxylic ester can provide useful effect like this, and it is the representative to various beauty treatment section's diseases and other beneficial effects of dermatosis indication.
[0138] embodiment 10
[0139] makes lignocaine 5g be dissolved among the warm propylene glycol 20ml and make so the solution that obtains mixes with the ointment of 50 parts of 75g confession mineral tallows, 40 parts in mineral oil and 10 parts of preparations of cera alba.Therefore the compositions of preparation contains 5% lignocaine can not washing in the ointment.
[0140] 5% lidocaine ointment agent more than the local application on the lip of the male subject at an age 73.A few minutes the posterior lip stolidity and insensible numb effect continue several hours.Such numbness or anesthetic action are different from sensation and the consciousness effect that is produced by hydroxyl-polycarboxylate fully.
[0141] embodiment 11
[0142] citric acid three propyl ester 10g are mixed with the ointment of 50 parts of 90g confession mineral tallows, 40 parts in mineral oil and 10 parts of preparations of cera alba.Therefore the compositions of preparation contains 10% citric acid, three propyl ester can not washing in the ointment.
[0143] 10% citric acid, three propyl ester ointments more than the local application on the lip of the male subject at an age 73.A few minutes posterior lip experienced lasting about 1.5-about 2 hours sensation and consciousness.Effect to nervus labialis shows that another kind of monohydroxy tricarboxylic ester can provide useful effect like this, and it is the representative to various beauty treatment section's diseases and other beneficial effects of dermatosis indication.
[0144] embodiment 12
[0145] citric acid three propyl ester 10g and propylene glycol 20ml are mixed with hydrophilic ointment or oil in water emulsion 70g.Therefore the compositions of preparation contains 10% citric acid, three propyl ester in water-soluble oil in water emulsion.
[0146], suffers from allergic eczema and follow on male patient's the right lower limb of following pruritus eczema damage of serious skin pruritus above 10% citric acid, three propyl ester of local application an age 73.After a few minutes, the pruritus complete obiteration also keeps not having pruritus at 4 hours subsequently skin.The different monohydroxy tricarboxylic ester that this result is presented in the different preparations can provide useful antipruritic effect, and it is the representative to various beauty treatment section's diseases and other beneficial effects of dermatosis indication.
[0147] embodiment 13
[0148] citric acid three isopropyl ester 10g are mixed with the ointment of 50 parts of 90g confession mineral tallows, 40 parts in mineral oil and 10 parts of preparations of cera alba.Therefore the compositions of preparation contains 10% citric acid, three isopropyl esters can not washing in the ointment.
[0149] 10% citric acid, three isopropyl ester ointments more than the local application on the lip of the male subject at an age 74.A few minutes posterior lip experienced and continued about 1 hour sensation and consciousness.This result shows that different monohydroxy tricarboxylic esters can provide useful effect, and it is the representative to various beauty treatment section's diseases and other beneficial effects of dermatosis indication.
[0150] embodiment 14
[0151] tribenzyl citrate 10g is mixed with the ointment of 50 parts of 90g confession mineral tallows, 40 parts in mineral oil and 10 parts of preparations of cera alba.Therefore the compositions of preparation contains 10% tribenzyl citrate can not washing in the ointment.
[0152] 10% tribenzyl citrate ointment more than the local application on the lip of the male subject at an age 74.A few minutes posterior lip experienced slight sensation and consciousness.That this result shows is different, aromatics monohydroxy tricarboxylic ester can provide useful effect, and it is the representative to various beauty treatment section's diseases and other beneficial effects of dermatosis indication.
[0153] embodiment 15
[0154] a kind of typical associating compositions of following preparation.
Hydrocortisone-17-valerate 0.2g is dissolved among liquid triethyl citrate 15g and the propylene glycol 10ml.The solution that makes so obtain mixes with the ointment of 50 parts of 74.8g confession mineral tallows, 40 parts in mineral oil and 10 parts of preparations of cera alba.Therefore the compositions of preparation contains 15% triethyl citrate and 0.2% hydrocortisone-17-valerate can not washing in the ointment.
[0155] the above ointment of local application on the male patient's at an age 74 pruritus and eczema skin.Pruritus disappears after a few minutes, and compositions has antiinflammatory action in addition.The result shows that said composition is useful to topical therapeutic pruritus, eczema and other inflammatory dermatosiss.
[0156] embodiment 16
[0157] the another kind of typical associating compositions of following preparation.
Make menthol 1g be dissolved in liquid citric acid three isopropyl ester 10g and and propylene glycol 10ml in.The solution that makes so obtain mixes with the ointment of 50 parts of 79g confession mineral tallows, 40 parts in mineral oil and 10 parts of preparations of cera alba.Therefore the compositions of preparation contains 10% citric acid, three isopropyl esters and 1% menthol can not washing in the ointment.
[0158] the above ointment of local application on the male patient's at an age 74 pruritus and eczema skin.Pruritus weakens after a few minutes, and compositions has the effect of alleviating to eczema damage.The result shows that said composition is useful to topical therapeutic pruritus, eczema and other inflammatory dermatosiss.
[0159] embodiment 17
[0160] the another kind of typical associating compositions of following preparation.
Make among the water-soluble 100ml of diphhydramine hydrochloride 58g (0.2 mole) and follow to stir and slowly add 5N NaOH 40ml (0.2 mole) down.Formation is as the diphenhydramine free alkali of oily white precipitate.Do not have separated free alkali, the limit is stirred and add N-acetyl group-L-proline-4 8g (0.3 mole) and N-acetyl group-D-glycosamine 44g (0.2 mole) down in oily mixture, and mixture becomes clear and bright solution.Add propylene glycol 100ml and water 50ml so that cumulative volume is 400ml (444g).Said preparation contains diphenhydramine 14.5%, N-acetyl group-L-proline 12% and the N-acetyl group-D-glycosamine 11% in propylene glycol/water solution.Above preparation 22g and tribenzyl citrate 10g are mixed with hydrophilic ointment or oil-in-water cream 68g.Therefore the compositions of preparation has pH 3.8 and contains at 10% tribenzyl citrate, 3% diphenhydramine, 2.6%N-acetyl group-L-proline and the 2.4%N-acetyl group-D-glycosamine that can wash in the cream.
[0161] the above compositions of local application on the male patient's at an age 74 pruritus and eczema skin.Pruritus disappears after a few minutes.The result shows that said composition is useful to topical therapeutic pruritus, eczema and other inflammatory dermatosiss.
[0162] it will be appreciated by those skilled in the art that to make and change and do not deviate from the inventive concept of its wide region embodiment described above.Therefore, should be appreciated that to the invention is not restricted to disclosed specific embodiments, and plan comprises as the change in the spirit and scope of the invention of accessory claim book definition.

Claims (26)

1.一种用于对患者的与美容科病症、牙科适应症、另一种病症及皮肤病适应症中的至少一种相关的神经产生有益作用的方法,所述方法包括将有效产生有益作用的量的羟基-多羧酸酯局部施用于患者的需要所述有益作用的区域,其中所述有益作用为对神经的感觉作用和轻度麻醉作用中的至少一种。1. A method for producing a beneficial effect on the nerves of a patient associated with at least one of a cosmetic condition, a dental condition, another condition and a dermatological condition, said method comprising applying a substance effective to produce a beneficial effect A hydroxy-polycarboxylate is topically administered to an area of a patient in need of said beneficial effect, wherein said beneficial effect is at least one of a sensory effect on a nerve and a mild anesthetic effect. 2.权利要求1的方法,其中所述神经与粘膜皮肤部位或器官有关。2. The method of claim 1, wherein said nerve is associated with a mucocutaneous site or organ. 3.权利要求2的方法,其中所述粘膜皮肤部位或器官选自患者的唇、口、齿龈、鼻孔、乳头、女阴、阴道、阴茎和肛门中的至少一种。3. The method of claim 2, wherein the mucocutaneous site or organ is selected from at least one of the patient's lips, mouth, gums, nostrils, nipples, vulva, vagina, penis, and anus. 4.权利要求1的方法,其中所述羟基-多羧酸酯选自羟基二羧酸酯和羟基三羧酸酯。4. The method of claim 1, wherein said hydroxy-polycarboxylate is selected from the group consisting of hydroxydicarboxylates and hydroxytricarboxylates. 5.权利要求4的方法,其中所述羟基-多羧酸酯为羟基三羧酸酯。5. The method of claim 4, wherein the hydroxy-polycarboxylate is a hydroxytricarboxylate. 6.权利要求5的方法,其中所述羟基三羧酸酯选自单羟基三羧酸酯、二羟基三羧酸酯和三羟基三羧酸酯。6. The method of claim 5, wherein the hydroxytricarboxylate is selected from the group consisting of monohydroxytricarboxylates, dihydroxytricarboxylates and trihydroxytricarboxylates. 7.权利要求5的方法,其中所述羟基三羧酸酯选自柠檬酸酯、异柠檬酸酯、高柠檬酸酯、高异柠檬酸酯、羟基柠檬酸酯、羟基异柠檬酸酯、羟基高柠檬酸酯、羟基高异柠檬酸酯、4,5-二羟基-3-羧基己-1,6-二酸酯、二羟基柠檬酸酯、二羟基高柠檬酸酯和二羟基高异柠檬酸酯。7. The method of claim 5, wherein the hydroxytricarboxylate is selected from the group consisting of citrate, isocitrate, homocitrate, homoisocitrate, hydroxycitrate, hydroxyisocitrate, hydroxy Homocitrate, Hydroxyhomoisocitrate, 4,5-Dihydroxy-3-carboxyhexane-1,6-dioate, Dihydroxyhomocitrate, Dihydroxyhomoisocitrate, and Dihydroxyhomoisocitrate esters. 8.权利要求1的方法,所述方法还包括给予局部活性药物用于与羟基-多羧酸酯产生协同或增效作用。8. The method of claim 1, further comprising administering a topically active drug for synergistic or synergistic effect with the hydroxy-polycarboxylate. 9.权利要求8的方法,其中所述局部活性药物选自羟基酸、酮酸和相关化合物;苯基α酰氧基链烷酸及衍生物、N-酰基-醛糖胺、N-酰基氨基酸和相关的N-酰基化合物;局部止痛药、局部麻醉药;抗痤疮药;抗菌药;抗酵母药;抗真菌药;抗病毒药;抗感染药;抗头皮屑药;抗皮炎药;抗湿疹药;抗组胺药;抗瘙痒药;止吐药;抗运动病药;抗炎药;抗表皮角化病药;止汗药;抗银屑病药;抗酒渣鼻药;抗皮脂溢药;毛发调理剂;毛发治疗药;抗皱药;抗焦虑药;抗惊厥药;抗抑郁药;遮光剂;防晒剂;亮肤剂;脱色剂;收敛药;清洁剂;鸡眼、骨痂或疣去除剂;皮肤丰满剂;皮肤丰盈保湿剂;紧肤剂;基质金属蛋白酶(MMP)抑制剂;局部用心血管药;伤口愈合剂;牙龈病或口腔护理药;氨基酸;肽;二肽;三肽;谷胱甘肽及其衍生物;寡肽;多肽;糖;氨基糖;维生素;皮质类固醇;鞣剂;激素和类视黄醇。9. The method of claim 8, wherein said topically active drug is selected from the group consisting of hydroxyacids, ketoacids and related compounds; phenyl alpha acyloxyalkanoic acids and derivatives, N-acyl-aldosamines, N-acylamino acids and related N-acyl compounds; topical analgesics, local anesthetics; antiacne; antibacterial; antiyeast; antifungal; antiviral; antiinfective; antidandruff; antidermatitis; antieczema Antihistamine; Antipruritic; Antiemetic; Antimotion sickness; Antiinflammatory; Antikeratosis; Antiperspirant; Antipsoriatic; Antirosacea; Antiseborrhea medicine; hair conditioner; hair treatment medicine; anti-wrinkle medicine; anxiolytic medicine; anticonvulsant medicine; antidepressant medicine; sunscreen; sunscreen; skin lightening medicine; depigmenting medicine; astringent; cleanser; corns, calluses or warts Remover; Skin Plumping Agent; Skin Plumping Moisturizer; Skin Firming Agent; Matrix Metalloproteinase (MMP) Inhibitor; Topical Cardiovascular Agent; Wound Healing Agent; Gum Disease or Oral Care Agent; Amino Acid; Peptide; Dipeptide; Tripeptide ; glutathione and its derivatives; oligopeptides; polypeptides; sugars; amino sugars; vitamins; corticosteroids; tanning agents; hormones and retinoids. 10.一种治疗患者的美容科病症或皮肤病适应症而不是与衰老有关的皮肤病的方法,该方法包括对患者的遭受病症或适应症侵袭的区域局部施用有效治疗所述病症的量的羟基-多羧酸酯。10. A method of treating a cosmetic condition or dermatological condition in a patient other than a dermatological condition associated with aging, the method comprising topically administering to an area of the patient affected by the condition or indication an amount effective to treat said condition Hydroxy-polycarboxylates. 11.权利要求10的方法,其中所述羟基-多羧酸酯选自羟基二羧酸酯和羟基三羧酸酯。11. The method of claim 10, wherein said hydroxy-polycarboxylate is selected from the group consisting of hydroxydicarboxylates and hydroxytricarboxylates. 12.权利要求11的方法,其中所述羟基-多羧酸酯为羟基三羧酸酯。12. The method of claim 11, wherein the hydroxy-polycarboxylate is a hydroxytricarboxylate. 13.权利要求10的方法,其中所述美容科病症或皮肤病适应症选自痤疮;酒渣鼻;有瑕疵的皮肤;蜂窝织炎;皮肤病;皮炎;皮肤或指甲感染;头皮屑;皮肤干燥;干燥病;湿疹;疱疹;鱼鳞癣;胡须假毛囊炎;瘙痒;牛皮癣;妊娠纹;疣;口腔或齿龈病;刺激性、炎性、不健康的、损伤的或异常的粘膜、皮肤、毛发、指甲、鼻孔、耳道、肛门或阴道病症;皮肤、指甲和毛发表面不平滑和粗糙;反应性、刺激性或毛细血管扩张性皮肤;用于皮肤漂白和增亮以及伤口愈合。13. The method of claim 10, wherein the cosmetic condition or dermatological indication is selected from acne; rosacea; blemish skin; cellulitis; dermatosis; dermatitis; skin or nail infection; Dryness; xerosis; eczema; herpes; ichthyosis; pseudofolliculitis beard; pruritus; psoriasis; stretch marks; warts; oral or gum disease; irritated, inflammatory, unhealthy, damaged or abnormal mucous membranes, skin, hair , nails, nostrils, ear canal, anal or vaginal conditions; uneven and rough skin, nails and hair surfaces; reactive, irritated or telangiectatic skin; for skin bleaching and lightening and wound healing. 14.权利要求10的方法,该方法还包括给予局部活性药物,用于与羟基-多羧酸酯产生协同或增效作用。14. The method of claim 10, further comprising administering a topically active drug for synergistic or synergistic effect with the hydroxy-polycarboxylate. 15.一种在患者中治疗粘膜皮肤损伤或皮肤损伤的方法,该方法包括以有效治疗损伤的量在损伤处局部施用羟基-多羧酸酯。15. A method of treating a mucocutaneous lesion or a skin lesion in a patient comprising topically applying a hydroxy-polycarboxylate to the lesion in an amount effective to treat the lesion. 16.权利要求15的方法,其中羟基-多羧酸酯选自羟基二羧酸酯和羟基三羧酸酯。16. The method of claim 15, wherein the hydroxy-polycarboxylate is selected from the group consisting of hydroxydicarboxylates and hydroxytricarboxylates. 17.权利要求16的方法,其中羟基-多羧酸酯为羟基三羧酸酯。17. The method of claim 16, wherein the hydroxy-polycarboxylate is a hydroxytricarboxylate. 18.权利要求15的方法,该方法还包括给予局部活性药物,用于与羟基-多羧酸酯产生协同或增效作用。18. The method of claim 15, further comprising administering a topically active drug for synergistic or synergistic effect with the hydroxy-polycarboxylate. 19.一种在患者中治疗与伤口愈合和粘膜皮肤器官或部位的疾病有关的疼痛、感染和炎症中的至少一种的方法,该方法包括以有效治疗疼痛、感染和炎症中的至少一种的量,在患者的遭受与伤口愈合和粘膜皮肤器官或部位的疾病有关的疼痛、感染和炎症中的至少一种侵袭的区域局部施用羟基-多羧酸酯。19. A method of treating at least one of pain, infection, and inflammation associated with wound healing and disease of mucocutaneous organs or sites in a patient, the method comprising treating at least one of pain, infection, and inflammation effectively The amount of hydroxy-polycarboxylate is topically applied to the area of the patient suffering from at least one of pain, infection and inflammation related to wound healing and disease of mucocutaneous organs or parts. 20.权利要求19的方法,其中羟基-多羧酸酯选自羟基二羧酸酯和羟基三羧酸酯。20. The method of claim 19, wherein the hydroxy-polycarboxylate is selected from the group consisting of hydroxydicarboxylates and hydroxytricarboxylates. 21.权利要求20的方法,其中羟基-多羧酸酯为羟基三羧酸酯。21. The method of claim 20, wherein the hydroxy-polycarboxylate is a hydroxytricarboxylate. 22.权利要求19的方法,该方法还包括给予局部活性药物,用于与羟基-多羧酸酯产生协同或增效作用。22. The method of claim 19, further comprising administering a topically active drug for synergistic or synergistic effect with the hydroxy-polycarboxylate. 23.一种包含羟基-多羧酸酯的组合物,该组合物被配制用于局部给予粘膜皮肤器官或部位,以对局部施用组合物的患者的神经产生有益的感觉和轻度麻醉作用中的至少一种。23. A composition comprising a hydroxy-polycarboxylate formulated for topical administration to a mucocutaneous organ or site for beneficial sensory and mild anesthetic effects on the nerves of a patient to whom the composition is topically applied at least one of . 24.权利要求23的方法,其中羟基-多羧酸酯选自羟基二羧酸酯和羟基三羧酸酯。24. The method of claim 23, wherein the hydroxy-polycarboxylate is selected from the group consisting of hydroxydicarboxylates and hydroxytricarboxylates. 25.权利要求24的方法,其中羟基-多羧酸酯为羟基三羧酸酯。25. The method of claim 24, wherein the hydroxy-polycarboxylate is a hydroxytricarboxylate. 26.权利要求23的组合物,该组合物还包含用于与羟基-多羧酸酯产生协同或增效作用的局部活性药物。26. The composition of claim 23, further comprising a topically active drug for synergistic or synergistic effect with the hydroxy-polycarboxylate.
CNA2006800476420A 2005-10-17 2006-10-13 Hydroxy-polycarboxylic acid esters: action on nerves and use on skin and mucocutaneous organs or sites Pending CN101330911A (en)

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* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN115919683A (en) * 2023-01-05 2023-04-07 上海其然生物科技有限公司 A kind of transparent composition and its preparation method and application

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN115919683A (en) * 2023-01-05 2023-04-07 上海其然生物科技有限公司 A kind of transparent composition and its preparation method and application
CN115919683B (en) * 2023-01-05 2024-11-12 上海其然生物科技有限公司 A transparent composition and its preparation method and application

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