TW580493B - Oxa diacids and related compounds for treating skin conditions - Google Patents

Abstract

Described are the use of compounds of formula (I), depicted below, as active principals for treating skin conditions; compositions containing these compounds; and methods of treating skin conditions using these compounds and compositions. Wherein R4 is (CR5R6-CR7R8-X1)n-CR9R10-C(=X2)X3R11, n is an integer from 1 to 18; R1, R2, R3, R5, R6, R7, R8, R9, R10 and R11, are independently, hydrogen or non-hydrogen substituents; and X, X1, X2, X3, Y and Z are independently, O, NH, or S.

Description

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Printed by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs 580493 -----______ B7 V. Description of Invention (1) — " — ~~ Related Applications This application is the application series N 0 · 〇8 / 6 3 6, Part of the continuous case of '540' should be filed on April 25, 1996, and the review is pending. BACKGROUND OF THE INVENTION I. Scope of the Invention + The invention relates to a novel compound ' composition containing these compounds as an active ingredient for topical treatment of a skin condition and methods of using the compounds and compositions for the treatment of skin conditions. Such compounds include compounds of formula (1): ‘R4 where R4 is, η is an integer from 1 to 1 8; Ri, R2, R3, r5, r6, r7, r8,

Rg, R i G and R ii are independently hydrogen or non-hydrogen substituents, preferably non-hydrogen substituents include alkyl, fluorenyl, oxaalkyl, aralkyl, and aryl; and X, X, X2 , X3, Y, and Z are independently 0, NH, or S, preferably X, X !, X2, X3, Y, and Z are oxygen in their equations, and Ri, r2, r3, R5, R6, R7 , Rs, R9, R10 and Ru are each a compound of hydrogen. II. The previous art shows that α-hydroxy acid for skin with a complete carbon backbone has been described in US Patent-4-This paper size applies Chinese National Standard (CNS) Α4 Regulations (210 '乂 297 public ^ "' ~~- -(Please read the notes on the back before filling out this page; >, 11 4 580493 Printed by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs 5. Description of the invention (2 cases N ο · 5 · Ο 9 1, 1 7 1 Cosmetic compositions using 2-hydroxyenoic acid are also disclosed in, for example, U.S. Patent No. 0.5, 108, 751. These compositions must have unsubstituted α-hydroxyl groups on the carbon backbone and be dedicated to provide Skin benefits. However, since most forms of α-hydroxy acids are known to cause skin irritation, such as glycolic acid and lactic acid, hydroxy acids need to be operated at a low pH, which results in a gradual reduction in the use of α _ Hydroxy acids. Topical formulations consisting of dicarboxylic acids with straight-chain full-carbon backbones have been introduced as alternatives to alpha-kisaka. For example, U.S. Patent No. ν 04'292,326'Nο · 3,86 , 104 and No. 5,3 85,943 both specify 7 to 13 Atom-blocking dicarboxylic acids are used in the treatment of a variety of different skin conditions. Similarly, 'U.S. Patent No. 4,8,8,5,8,2 shows that dicarboxylic acids of 4 to 18 carbon atoms are suitable for use in the field. Treatment of skin lesions. The problem with the use of these dicarboxylic acids is their insolubility in aqueous solutions. These liquids account for a large part of the cosmetic delivery system. At the same time, the dicarbonic acid, which is a complete carbon backbone, is solid at ambient temperature and is not easy. Treatment; if a solution is to be formed, the result is an aesthetically unacceptable mixture for cosmetic use. Therefore, there must be one or a class of mild, exfoliating compounds used as topical skin treatments. • A gentleness is also needed A topical composition with exfoliating effect; it contains a water-soluble compound that can be made into an aesthetically acceptable cosmetic or skin product. Summary of the Invention The purpose of this month is to provide a water-soluble compound or a class of such compounds that can be made aesthetically A school-acceptable mild, exfoliating topical composition. Another object of the present invention is to provide a topical group with multiple skin care effects-5-

I-^ ---; ----- 丨 丨 (Please read the notes on the back before filling in this page), 1T Φ Lake 493 Five A7 B7, Invention description (3 compounds Another item of the present invention is to Oxy diacids provide novel dermatological and cosmetic uses. These and other purposes are described below. The detailed description 1 The basic compound of the present invention is a compound of the formula ():

(I) Clothing-(Please read the notes on the back before filling out this page) Printed by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs where R4 is (CUCRA-XOn-CRpRio-CpXdXsR ", an integer of n 疋 1 to 18; , R2, R3, r5, R6, r7, r8, R 9, R1 0 and RM are independently hydrogen or non-hydrogen substituents. X, X, X2, X3, Y and Z are independently 0, NH or S. Preferred Is a compound in which X, χ, χ2, χ3, γ, and Z are all oxygen in their equations. The best is that X, χ, χ2, χ3, γ, and Z are oxygen in their equations, and R1, R2 , R3, R5, R6, R7, R8, R9, R10, and Ru are each a compound of hydrogen. Preferred non-hydrogen substituents include alkyl, alkenyl, oxaalkyl, aralkyl, and aryl. Non-hydrogen substitution Examples include methyl, ethyl, propyl, isopropyl, butyl, isobutyl, hexyl, heptyl, octyl, nonyl, dodecyl, methoxy, ethoxy, propoxy , Butoxy, cyclohexenyl, hydroxymethyl, hydroxy-6- This paper size applies to China National Standard (CNS) A4 (210X 297 mm)

Printed by the Consumer Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs, 1T 580493 A7 B7 V. Description of the Invention (5) Miscellaneous-Carbon Diacid (HOOC-CH2-S-CH2-CH2-S-CH2 · CH2-S-CH2 -COOH), 3,6 · dithia_9,12 · dioxa · tetradecanedioic acid (H00C-CH2-S-CH2-CH2-S-CH2-CH2-0-CH2-CH2-0 -CH2-C00H), 3-amino · 6,9-dioxa-undecanedicarboxylic acid monoammoniumamine (hooc_ch2-nh-ch2-ch2-o-ch2- CH2_0-CH2-CO_NH2), 3- Amine_6,9 · dioxa-undecyldicarbonate dihydrazide (112: ^-〇 < :-(: 112-: ^ 11-0: 112-(: 112-〇- (: 112 · CH2-〇-CH2-CONH2), 3,6,9-trioxa-undecane diacid monoreel (1100 €:-(: 112_0-. 112_ (: 112-0_ (: 112- (: 112-0-(: 112-CONH2), 3,6,9-trioxa · undecanedioic acid dihydrazide)! ^! ^^ ch2_o-ch2_ch2_o-ch2-ch2_o_ch2-conh2), 2 , 10-dimethyl-3,6,9-trioxaundecanedicarboxylic acid (1 ^ 〇〇 (:-(: 11- (ch3) -o-ch2_ch2-o_ch2_ch2-o_ch (ch3) _cooh ), And 2,10-monomethyl-3,9-dithia-6-oxaundecadecanedioic acid (hooc-ch (ch3) -s_ch2-ch2-o-ch2_ch2-s-ch (ch3 )-COOH). US Patent No. 5,017,675 5,319,004 states that the compounds of formula (I) are suitable as intermediates for curing agents and hardeners in the manufacture of epoxy resins. Both patents were awarded to Hoechst AG in Germany. German publication application NO. DE_A- 2936123 illustrates the preparation method of these epoxy resin intermediates. These compounds can also be purchased from the German Hertz company. Compounds of formula (I) can also be obtained from commercially available polyamines, polyhydric alcohols and polythiols. Routine chemical reactions known in this technique, such as hydrazine • 8 _ I Paper size applies Chinese National Standard (CNS) A4 Regulations --- (Please read the precautions on the back before filling this page)

、 1T 4 580493 Printed by the Consumer Cooperatives of the Central Bureau of Standards of the Ministry of Economic Affairs A7 B7 I ----——-_ _____, Description of Invention (6) Use, Catalytic Oxidation, Esterification and other conventional organic chemistry Preparation by synthetic methods, etc. These methods are described in reference books on organic chemistry, including March's Advanced Organic Chemistry · Reactions, Machines, Third Edition, 'Jonh Wiley Interscienee;) (; l9W;) and Advanced Organic Chemistry by Carey et al., Third Edition, Part A * B ', Plenum Press, New York (1990). The oxygen-containing compounds suitable for use in the topical composition of the present invention may also be in the form of derivatives, which can be converted back to the acidic form when they are subjected to the hydrolysis enzymes of the skin. These enzymes are, for example, glycosidases, phosphatases, g enzymes, and amidases. Examples of suitable derivatives include esters formed from compounds of formula I with aliphatic alcohols, carbohydrates, amines, lactones, and anhydrides. All compounds of formula I and their derivatives as defined herein may be collectively referred to as "oxyacids" and / or "oxygenates, and / or" oxyacids "." Local application "means on the skin Directly on the surface of the skin. "Composition for local shao" means a composition for directly applying or coating on the surface of the skin. "Effective amount" means that the compound or composition can be effectively used for treatment. Skin conditions, such as: positively altered doses of skin conditions that cause, or are accompanied by, or exacerbated by, exfoliation (eg, normal exfoliation), "physiologically acceptable carriers" or "suitable A topical carrier is a drug, cosmetic, medical product, or inert ingredient that is suitable for direct contact with human tissues and has no undue toxicity. All percentages refer to weight percentages relative to the total weight of the topical composition. According to the present invention, an oxygen-containing compound is used as an active ingredient for topical application, and is used to treat various abnormal peelings that cause, accompany, or worsen. -9- This paper size applies the Chinese National Standard (CNS) A4 specification ( 210X297 mm) IT (Please read the precautions on the back before filling out this page) 580493 Printed by A7, Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs 5. Description of the invention (7) Skin disorders. These conditions include, but are not limited to: dry skin, ichthyosis, keratinization of the skin of the hands and feet, dandruff, chronic lichen simplex, follicular keratosis, keratosis, freckles, age spots, melanosis, skin spots, facial blisters , Psoriasis, eczema, purpura, inflammatory dermatitis, dilatation of abdominal lines (such as stretch marks), warts and skin cocoons. Unexpectedly, compounds such as guns were unexpectedly found to be suitable as active agents in topical preparations for the treatment of skin older symptoms such as light-induced aging and internal aging, including skin wrinkles such as fine lines around the eyes or " Difficult foot marks "or fine lines around the mouth, irregular pigmentation, swelling, loss of skin resilience and elasticity. Oxygen compounds and topical compositions containing them are also suitable for the treatment of nail finger follicle and hair related symptoms, such as the removal of ingrown hairs, folliculitis and pseudofolliculitis. The compound can also soften hair and accelerate the removal of ingrown hair, so the formula is used in shaving compositions. The oxygen-containing compound may be incorporated into the composition as a free acid or a corresponding salt derived from the neutralization of an organic or inorganic base. Such organic or inorganic bases such as triethanolamine, arginine, lysine, hydrogen Oxygen, sodium hydroxide, ammonium hydroxide and ammonium hydroxide. When combined with a physiologically acceptable carrier into a topical composition, the effectiveness of the oxygen-containing compound may be in the range of about 0.1 to about 95%, and both the effective amount and the frequency of the drug must be treated according to the The age and physical condition of the recipient of a specific skin condition, the severity of the condition, the period of treatment, the characteristics of the concurrent therapy, the specific compound or composition used, the compound or group used to deliver the compound (CNS) Α4 gauge (210 > < 297 male 17 ^ ~~--_ (read the precautions on the back before filling in this page)

1.1T printed by the Consumer Cooperative of the Central Standard Bureau of the Ministry of Economic Affairs 580493 kl _______ B7 —---- ------- V. Description of the invention (8) ~ 'Specific carrier of the compound and expert practice familiar with this technique Other known factors vary. It has been found that the efficacy of oxygenated compounds in the treatment of skin conditions is affected by the acid test of the composition. It is believed that the pH value of the composition should be maintained in an acid range of less than 7 and the pH value is preferably less than 5 and the most preferred range is 5 to 4 · 0 · acid value. The pH of the composition can be adjusted by adding water-soluble salts. This salt is tested by strong tests (for example: 〇〇η, Na 〇 Ο, ΝΗ Ο Η) and weak acids (such as: acetic acid, lactic acid, acetic acid) And carbonic acid). Examples of such salts include potassium hydrogen phosphate, sodium phosphate, sodium acetate, sodium lactate, and the like. Other methods suitable for adjusting the pH of the topical composition are known to those skilled in the art. The present invention and composition have clear advantages over alpha-hydroxy acid formulations, including excellent mildness. When applied to the face, formulations containing alpha-hydroxy acids (such as glycolic acid and lactic acid) can cause some people to feel quite uncomfortable and severely irritate their skin. For example, a formulation containing 4% acetic acid, pH 3.7, and a skin allergy (PII) score of 0.2 in the 20 test groups was 0.23. In contrast, formulations with 10% 3,6,9-trioxaundecanedicarboxylic acid and acid-base ratios less than 3.7 have a ρ π fraction of only 0.13 (see Example 2 below). Compositions with a PII less than or equal to 0 · 15 were all non-irritating, while those with ρ π between 0 · 15 and 0 · 3 were moderately irritating; as for the PII score in the test group, A composition of 3.0 is considered severely irritating. The PIL score is determined by factors such as the irritating condition in the subject < The number of subjects is relative to the total number of subjects. -11-This paper size applies to Chinese national standards (CNsl Α4 size (2Η) × 297 mm) ^ ^ ^ Clothing ------ 1T ------ (Please read the precautions on the back before filling in this Page) 580493 Μ B7 Printed by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs 5. Description of the invention (9 Compared with the glycolic acid formulation, the oxygenated diacid composition of the present invention is not only milder on the skin but also highly effective In order to normalize the exfoliating effect of the upper stratum corneum, which is an activity necessary to alleviate the aforementioned skin symptoms, the composition for local use of the present invention has better advantages than the composition containing diquinic acid, including better water solubility and Better exfoliation of cuticle. Oxygen-containing monoacid is easily soluble in water at a concentration of at least 20 to 30% by weight; therefore, the composition has a wide range of elasticity. It has a long chain length in the straight full carbon backbone The dicarboxylic acid is insoluble in water and other aesthetically acceptable carriers. This severely limits the selectivity of the dicarboxylic acid carrier. The peeling effect of these dicarboxylic acids is also problematic. For example: containing 50 / 〇 and 10% 的 ardodecane dicarboxylic acid, Any normalizing effect on the exfoliation of the cuticle skin epidermis is no better than its carrier alone. Some specific carrier examples have been found to be suitable for use with oxygenates, including: (1) (a) about 2 weight percent to about 10 weight percent glycerol; (b) about 1 weight percent to about 10 weight percent propylene glycol; (c) about 0 weight percent to about 2 weight percent hydroxyethyl cellulose; (4) About 0.01 wt% to about 1 wt% of imidazolidinyl urea; (6) about 0.01 wt% to about 2 wt% of disodium ED TA. (• 2) (a) about 1 wt% to about 10 Weight percent glycerol; (b) about 1 weight percent to about 10 weight percent propylene glycol; ((about 1 weight percent to about 10 weight percent octyl palmitate; (about 1 weight percent to about 10 weight percent) Myristyl myristic acid; (e) cetylstearyl alcohol / Ceteareth_ -12- about 1% by weight to about 6% by weight-this paper size applies to Chinese National Standard (CNS) A4 orange (210 × 297 mm) ^ Clothing — (Please read the back first Please fill in this page again, 1T 580493 A7 B7 printed by the Consumer Cooperatives of the Central Bureau of Standards of the Ministry of Economic Affairs 5. Description of the invention (1〇) 2 0; (f) about 0.5 to 6 weight percent Glyceryl monostearate; (g) about 0.1 to about 2 weight percent of hydroxyethyl cellulose; (h) about 0.1 to about 1 weight percent of imidazolidinyl urea; about 0.05 Weight percent to about 0.5 weight percent of methylparaben and (j) about 0.01 weight percent to about 2 weight percent of EDT A-disodium; and (3) (a) about 2 weight percent to About 10 weight percent glycerol; (b) about 1 weight percent to about 10 weight percent octyl palmitate; (c) about i weight percent to about 10 weight percent myristyl myristate; (d) ) About 1 to about 7 weight percent of cetearyl alcohol / Ceteareth_20; (e) about 1 to about 10 weight percent of propylene glycol; (f) about 1 to about 6 weight percent of monostearate Acid glycerol vinegar; (g) about 0.1 weight percent to about 2 weight Fractional hydroxyethyl cellulose; (h) from about 0.1 weight percent to about 1 weight percent of imidazolium urea; (i) from about 0.05 weight percent to about 0.5 weight percent of para- paraben Esters; (j) EDTA- disodium in an amount of from about 0.01 to about 2 weight percent. The topical composition of the present invention can be made into a lotion. The first or more base lotions include about 0.1 to about 90%, preferably about 1 to about 50%, and most preferably about 5 to about 20% of the oxygenated diacid, and the remainder is water. The second lotion includes about 0.1 to about 90%, preferably about 1 to about 50%, most preferably about 5% to about 20% of the oxygenated diacid, about 0.5 to about 50% softener, and about 0.1 to about 30% emulsifier, the rest is water. The second lotion may also contain up to about 10% preservative, about 0.1 to about 3% perfume, and up to about 5% dye or pigment. -13- This paper size applies Chinese National Standard (CNS) A4 gauge (210X297 mm) ----; ----- 0 ^ ------ 1T ------ 0 (read first Read the notes on the back and fill in this page) 580493 A7 B7 V. Description of the invention (11) The topical composition of the present invention can also be formulated into a cream. The first or more basic creams contain about 0.1 to about 9 5 %, Preferably about 1 to about 50%, most preferably about 5% to about 20% of the oxygenated diacid, and the remainder is water. The second preferred cream contains about 0.1 to about 90%, preferably about} to about 50% / ❶, most preferably about 5% to about 20% of the oxygenated diacid, about 0.5 To about 50% softener, about 0 "to about 30% emulsifier, about 0.01 to about 6% thickener, and the rest is water. Oxygenated diacids can be combined with most conventional softening agents, including: mineral oil, petrolatum, paraffin, kerosene, paraffin, microcrystalline wax, perhydrosqualene dimethyl polyoxygen fired, toluene-based polysilicon Oxane, silicone-diol copolymer, triglyceride, acetylated monoglyceride, ethoxyglyceride, fatty acid alkyl ester, lipoic acid and its alcohols, lanolin and its derivatives, polyol Esters, sterols, beeswax derivatives, polyhydric alcohols and polyethers, and amines of fatty acids. Other suitable softeners can be found in Cosmetics and Acoustics Salad by Sagarin '2nd edition, Volume 1, pages 32 to 43 (1972), the contents of which are incorporated herein by reference. Printed by the Consumer Standards Cooperative of the Central Bureau of Standards of the Ministry of Economic Affairs-(Please read the notes on the back before filling out this page) Emulsifiers can be cationic, anionic, non-ionic, amphoteric, or combinations thereof. Nonionic emulsifiers are preferred. Examples of commercially available nonionic emulsifiers are: sorbitan, alkoxylated fatty alcohols, and alkyl polysaccharides. Anionic emulsifiers may include: bales, alkyl sulfates, mono- and di-alkyl phosphates, alkyl sulfonates, and isothiocarbonates. Other suitable emulsifiers can be found in McCutcheon's Detergents and Emulsifiers, North American Edition, pp. 317-324 (1986), the contents of which are incorporated herein by reference. Suitable preservatives for this composition include: alkanols, especially ethanol and _________ -14 _ This paper is suitable for financial standards (CNS) M specifications (21Q > < 297 public attack) — printed by the Consumer Cooperatives of the Central Bureau of Standards of the Ministry of Economic Affairs 580493 • kl ______ Β7 V. Description of the Invention (12) ~ ~ benzyl alcohol, parabens, sorbates, urea derivatives and isopropyl alcohol Oxazolidinone. These lotions or creams can be made using traditional homogenization methods known to those skilled in the art, but microfluidization methods can also be used, which involve the use of these creams and lotions < The water phase and oil phase are mixed in a high-pressure homogenizer, which greatly reduces the size of the emulsion particles to about 41% of the size of the cream and lotion particles prepared without high pressure. The microfluidization method can produce elegant and stable creams and lotions containing an effective amount of oxygenated diacid without the use of traditional emulsifiers and surfactants. The topical composition of the present invention can also be formulated into a microemulsion. The first basic microemulsion system comprises from about 0.1 to about 50%, preferably from about 1 to about 30%, most preferably from about 5% to about 20% of an oxoacid, and from about 0.05 to about 50%. About 20% hydrocarbons, about 0.5 to about 20% oil, and the remainder is water. A second more preferred microemulsion system includes from about 1 to about 20% oxygenated diacid, from about 0.5 to about 15% hydrocarbons, from about 10/0 to about 15% oil, from about 0.1 to about 10% lipid anti-alcohol, up to 30% non-ionic surfactant, the rest is water. The composition for local use of the present invention can be formulated into oil-in-water or water-in-oil emulsions, gels, lotions, ointments, nipples, sprays, adhesive tapes and patches. The composition of the present invention may also be a heterogeneous emulsion, such as a water-in-oil-in-water emulsion described in U.S. Patent No. 4,254,105, which has been incorporated herein by reference. The composition of the present invention can also be formulated into a crushed ketone liquid oil-in-water triple emulsion as described in U.S. Patent No. 4,960,764, which is incorporated herein by reference. The composition of the present invention can also be made into a microlipid formulation, for example, as described in Mezei in the Journal of Pharmaceutical and Pharmaceutical Sciences, Vol. 34, pp. 473 to 4 74-15. CNS) A4 specification (210X 297 mm) (please read the precautions on the back before filling out this page), 11 d Printed by the Consumers' Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs 580493 Μ --'---- B7 V. Description of the invention (13) A method of '2 9 8 2) or a method of amending it. In these compositions, the droplets of the oxygenated diacid solution can be embedded in the microcapsules of the microcapsules or other suitable lipids (such as lipoproteins) and the microcapsules of the microcapsules. When forming a topical composition, these microlipids can be edited in Brewer, pp. 345-358, according to Metz, Ei ^ vier Science Publishers Bv, New York (1 98 5 ), (The case has been incorporated as a reference material herein), the preparation mode, the method of use, and the composition of topical liposomes are added to any of the above carrier systems. Or according to Szoka et al. Described in Ib, "Vol. 75, p. 4194-4198 (I978) and Diploses et al. In Journal of the Society of Cosmetic Chemists, Vol. 43 Pp_93-100 (1992) 'Reverse-phase evaporation method in this case has been incorporated as reference material in this case. Oxydiacid solution can also be embedded in polymer vesicles, and its case is made of a suitable polymer, such as Gelatin, cross-linked gelatin, polyamide, polyacrylate, etc., cysts, and then incorporated into the topical composition. The composition of the present invention may include only oxygen-containing compounds as active ingredients, or may be used in combination with other cosmetics And pharmaceutical actives and excipients. Other suitable cosmetics and medicines include, but are not limited to, such as: fungicides, vitamins, sunscreens, carotenoids, anti-allergens, depigmentants, anti-inflammatory agents , Anesthetics, surfactants, humectants, shedding agents, stabilizers, preservatives, preservatives, thickeners, lubricants, humectants, chelating agents and skin penetration enhancers and emulsifiers, softeners, perfumes, and above Colorants discussed. Examples of thickeners, including: xanthan gum, xanthan gum salt water resistant to this paper. Applicable to Chinaϋs standard (CNS) A4 ^ T ^ 「〇x 297 meals ·） · Loading tr (please read the note on the back first) Please fill in this page again for matters) 580493 A7 __________ B7 V. Description of the invention (14) ~ '~ Agent, hydroxypropyl cellulose, hydroxyethyl cellulose, polycarboxylate and acacia gum, Sepigel 3〇 5 (from Seppic Co., France, Vee gum or magnesium stearate. In the 4th, and 4th, the oxygenated diacid is not only compatible with the humectant and can be used to improve it Utilization, wetting agents such as: urea, pcA, amino acids, certain polyols and other compounds with hygroscopic properties. Topical compositions can also be made to contain about 0.01 to about 90%, with about i It is preferably about 50% to about 50%; most preferably about 5 to about 2000/0 of oxygenated diacids, and exfoliating agents such as salicylic acid and benzamidine peroxide, and such as kojic acid benzoquinone, Skin brighteners of licorice derivatives, ascorbic acid and its derivatives (such as ascorbyl magnesium phosphate) and glyceric acid and its derivatives. Use from about 0.1 to about 90%, to 1 to about 50% is preferred; about 5 to about 20% is the best oxygenated diacid, combined with organic and inorganic sunscreen agents, such as: dioxide, zinc oxide, benzylidene camphor, anthranilide , Butylmethoxydibenzoylmethane, phenol sulfonate and cinnamic acid derivatives. Among them, butylmethoxydibenzoylmethane and cinnamic acid derivatives are preferred. Printed by the Consumer Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs —. Clothing-(Please read the notes on the back before filling out this page) Φ The topical composition of the present invention also contains about 〇 丨 to about 90% oxygenated diacid, preferably about 1 to about 50% About 5 to about 20% is optimal, and its co-formulation includes: (i) Retinoids such as: retinol, retinoic acid, retinyl standard acid, retinyl propionate , Retinyl acetate, isotretinoin, and synthetic retinoid mimics; (ii) hormone compounds, such as: estrogen triol, estrogen diol estrone, or conjugated estrogen; (丨 丨"Heartonic acid or polyhydroxy alpha-hydroxy acid, such as: glycolic acid, lactic acid, tartaric acid, gulonic acid and other carboxylic acids and their monomers, polymers, cyclic or Acyclic derivatives; (iv) a-keto acid, -17- This paper size applies to Chinese National Standard (CNS) A4 (210X297 mm) Printed by the Consumer Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs 580493 A7 B7 V. Invention Explanation (15) Such as: pyruvate, 2-oxopropionic acid, 2-oxobutyric acid, 2-oxopentanone, and the like. It is also possible to use about 0.1 to about 90%, preferably about 1 to about 50%; about 5 to about 20% of the best oxygenated diacids for topical use that contains one or more of the following materials to provide other benefits Formulations: (i) Vitamins, such as enzyme cofactors, such as: Vitamin B6, Vitamin B12, Vitamin D3, 1,25-dihydroxyvitamin D3, Vitamin B1., Vitamin B2, Vitamin K, Vitamin E, Fertility Trienols and their derivatives, nicotinic acid and its esters, pantothenic acid and its esters, pantothenic acid, folic acid and its derivatives, choline, carnitine, and informal vitamin states or "false, vitamin substances, For example: Vitamin F or cis, cis-linolenic acid, vitamin M or pteryl glutamic acid, vitamin B10 and vitamin B11, sesame seed factor, termitin, penicin, insectin ( insectine), hypomycin and mycoine, vitamin L or anthranilic acid, vitamin L2, adenosylthiomethylpentose, inositol, or cis-1, 2, 3, 5 -Trans-4-6-cyclohexanehexanol and its esters, especially phytic acid, laetrile, 1-is talonitrile- β-glucuronic acid, bitter almond tincture, vitamin B15 or panic acid, vitamin B13 or orotic acid, vitamin tin 3 and methyl sulfonium salt of hydrogen of procaine hydrochloride, vitamin U or methionine, and Pyrroloquinone; (ii) bactericides, including, for example, cleomycin (c 1 〇trima ζ ο 1 e), ketoconazole, miconazole, nadifen ( naftifine), tenaftate, amphotericin B, nystatin, 5-fluorocytopeptide-18- This paper applies Chinese National Standard (CNS) A4 Specifications (2i〇x297 feet) (Please read the notes on the back before filling out this page} Order 580493 Printed by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs A7 ___B7 V. Description of the invention (16) Pyridine, Griseofulvin, Halopropynyloxybenzenes, of which tenafil, halopropynyloxybenzenes and meconazine are the best; ('iii) self-staining agents, including, for example: dihydroxyacetone and Lawson's agent (LAWSONE) Methyl acetone is best; (iv) antimycobacterial agents, such as: erythromycin, tetracycline and related compounds, especially Doxycyclin and methacyclin, cephalosporin, penicillin, macrolides, peptide compounds such as' neomycin, vancomycin, oleandomycin, paroxin, leucomycin , Amphotericin (amphomycin) with macrolide molecules, quinolinone derivatives, and others that can inhibit fine cell wall synthesis, cell membrane function, RN A metabolism, purine, glutamate, and protein synthesis, respiration or phosphorylation Compounds. (v) topical analgesics, such as: lidocaine, benzocaine, butylcaine, tetracaine, triloba oil, and eugenol, with benzocaine and lidocaine being the best; (vi ) As essential lipid compounds for skin barrier function include, for example: Neuraminamine, essential fatty acids and their esters, especially glycerides, ① acyl fatty acid and its hydroxyl group with alkanol via carboxyl hydroxyl group or ω with other fatty acids The esters derived from the hydroxyl reaction are the best in the latter form. They are most suitable for phospholipids, cholesterol and their esters, such as cholestystyl succinate and cholestylate phosphate. Among them, it is best to distinguish cholestylate and essential fatty acids. , Plant sterols, choline alcohols and their derivatives. The lipid compound may be added to the topical composition as a separate molecule or as a lipid complex mixture derived from synthetic, animal or vegetable sources. -19- This paper size is suitable for 7 Guanjiapi (CNS) Congde (21Gx 297)-^^ binding (please read the precautions on the back before filling this page) 580493 Printed by the Consumer Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs A7 ___________ B7 V. Description of the invention (17) (vii) Anti-allergen agents and HI / or H2 anti-histamines, such as: diphenyl alcohol amine, clemizole, anti-histamine (antazoline), Dinalbitine, phenyltoloxamine citrate, tricyclic antiallergens, such as: ketotifene, dithiadene, and 3-pyrophene Sulfide, H2 receptor blocker, especially burimamide, metiamide and cimetidien, cromolic acid and salts thereof; (viii) Oxydiacids can be combined with topical anti-inflammatory agents to reduce inflammation. These anti-inflammatory agents are used at a concentration of from about 0.05 to about 10%, and preferably from 0.5 to about 1%. Its concentration can be adjusted upwards or downwards according to the efficacy of the medicament used. Examples of steroidal anti-inflammatory agents that can be used in combination with oxygenated diacids include: corticosteroid light base marks> to steroids, α-methyl dexamethasone, dexamethasone trans-acid salts, and beclamethasone ) Dipropionate, corticosteroid valerate, corticosteroid cyclopentylpropionate, dehydrocorticosteroids, and mixtures thereof, with dehydrocorticosteroids and cortisol being the best; and (ix ) Non-steroidal anti-inflammatory agents such as the anti-inflammatory and anti-rheumatic drugs described in Rain sf or d, Volumes 1 to 3, Boca Raton, Florida CRC Press (Boca Raton (1985) and explicit examples of suitable non-steroidal anti-inflammatory agents include, for example, oxicams (e.g., piroxicain, isoxicam), fenamic acid derivatives Materials, meclofenamate derivatives (for example: sodium melofenamate), flufenamic acid derivatives, mefenamic -20- This paper size applies to Chinese National Standards (CNS) A4 Regulations (210X297 mm) Clothing ------ 1T ------ (Please read the back first Note for refilling this page} Printed by the Central Bureau of Standards, Ministry of Economic Affairs and Consumer Cooperatives 580493 A7 ______B7 V. Description of the invention (18) acid) derivatives, propionates, such as: ibuprofen, nerol (Naproxen), benoxaprofen, flubiprofen, ketoprofen, and suprofen, of which isobuprofen is the best; of which pyrazosin Dione, of which phenylbutyrate is the best; acetic acid derivatives, such as: diclofenac, fenclofenac, indomethacin, and sulindac ), With mouth bow | mouth flower wine Xin best; salicylic acid derivatives, such as aspirin, disalicylic acid and benolate, among which aspirin and double salicylate The acid is the best. The composition of the present invention can also include safe anti-inflammatory products with natural origin and anti-inflammatory properties, such as aloe vera extract, IUbia Cordifolia extract, Commiphora Mukul extract, Willow bark, chamomile flower, arnica flower, yarrow root Greek tricolor and similar known to those skilled in the art. The local shao composition of the present invention may contain about 0.01 to about 90% oxodiacid, preferably about 1 to about 50%, most preferably about 5 to About 20%, with phenolic hydroxyl-functional antioxidants, such as: gallic acid derivatives (such as propyl gallate), biological I ketones (such as: quercetin, rutin, soy bean curd Progenitor, genistein), ferulic acid derivatives (such as ethyl ferulic acid, sodium ferulic acid), 6-hydroxy-2,5,7-tetramethylchroman 2 -retemic acid. The composition also contains effective concentrations of water-soluble antioxidants, such as: uric acid, reducing acid, tannic acid, rose block acid, and catechin. It is also beneficial to make it from about 0.01 to about 90%, and from about 1 to about 50% compared to -21 _ This paper is suitable for fiscal countries i ^ $ (CNS) M Na (η-97)- —- (Please read the notes on the back before filling out this page)-Yibu d Printed by the Consumers Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs 580493, A7 _ B7 V. Invention Description (19) Good, about 5 to about 20% It is best formulated with nitric oxide synthase inhibitors, which can reduce skin redness, vasodilation, and inflammatory reactions, especially in response to electromagnetic and ionizing radiation, or chemically or biologically aggressive compounds. The nitric oxide synthase inhibitor may be added at a concentration of about 0.005% to 10%, preferably 1 to 3%, and is selected from the group consisting of: guanidine derivatives, especially monoaminoguanidine and methylguanidine, L-arginine derivatives, in particular: ng_nitrospermine and its esters, N, monomethylspermine, 2-iminohexahydropyridine and other 2-iminoazepines ring. Other possible antioxidants that may be included in the composition are those with one or more thiol functions (-SH), which may be in reduced or non-reduced form, such as: glutathione, lipoic acid, thioglycolic acid, and other hydrogen Sulfur compounds. The concentration of hydrogen-sulfur-based antioxidants in cosmetics used in cosmetics should not exceed 0.5%, but in the case of pharmaceuticals, it can be higher than 0.5% if the effect is considered. The composition may also contain inorganic antioxidants, such as sulfites, bisulfites, metabisulfites or other inorganic salts, and acids containing sulfur in the normal tetravalent oxidation state. The concentration of the inorganic sulfur-containing antioxidant is preferably about 0% to about 0.5%, and the optimal concentration is between about 0.1 to about 0.4% by weight. The composition of the present invention also includes about 0.1 to about 90%, preferably about 1 to about 50%, and most preferably about 5 to about 20% of the oxygenated diacid, which can be mixed with about 0.025% To about 5%, preferably from about 0.5% to 2%, and most preferably from about 0.05 to about 1%, based on electron spin trapping compounds, such as nitrene, N-tert-butyl Nitrate and pyridinyl-1 · oxide) -N-third butyl nitrate or other compounds known to form free radicals with a half-life of more than one minute. -22- This paper size applies to China National Standard (CNS) A4 specifications (210, 乂 297 mm). IT installed (please read the precautions on the back before filling this page) 580493 Printed by the Consumer Standards Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs --- -B7 V. Description of the invention (20) --- ~~-In the composition containing insect repellent, about 0.01 to about 90% can also be used, preferably about 50% to about 50%, and the best about 5 to about 20% of oxygenated diacids. These insect repellents are, for example, aliphatic, cyclic or aromatic amidine, citronella oil, terpineol, eucalyptus brain, Indian tree oil and terephthalic acid. And its esters. Other suitable insect repellents can be found in US Department of Agriculture Technical Brochure No. 1 549 or US Department of Agriculture Nos. 69,340 and 461. The topical compositions containing oxodiacids of the present invention may also include skin cooling compounds such as, for example, menthol, menthol-based glycerol, asymmetric carbonates, thiocarbonates, and urethane N-substituted carboxylates. Phenamine, urea, or phosphine oxide, as described in the Journal of Cosmetic Chemists, Vol. 29, p. 158 (1978), menthol lactate, and menthol glycerol acetal. The general activity and mildness of the topical composition on the skin can also be enhanced by neutralizing to pH 3.5 to 7.0, and the optimal pH 3.7 to 5.6, which can use one or more of the amphoteric and pseudoamphoteric compounds , Such as: glycerin, alanine, valine, serine, thionine, methionine, leucine, asparagine, histidine, melamine, cooked amine, lysine, Amino acid, cysteine, tryptophan, serine, phenylalanine, citrulline, sarcosine, proline, 3- or 4-hydroxyproline, 5-hydroxylysine, Ornithine and its derivatives, 3-aminopropionic acid and other aminocarboxylic acids, cananosine, para-cananosine, high spermine, taurine, aminouronic acid and amino sugars , Aminouronic acid, aminouronic acid, deacetylated hyaluronic acid, hyaluronic acid, cartilage carbohydrate, dethiofluorenated heparin, neuraminic or salicylic acid, methionine sulfonium, alanine glycine Acid, chondroitin, D, L-sphingosine, sphingomyelin, snake meat peptide, glucagon, high carnosine, sylcerine, cocoa-23- This paper is applicable to China Standard (CNS) A4 specification (210X297 mm) (Please read the notes on the back before filling out this page) t-shirt., 11 d Printed by the Consumers Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs 580493 A7 _ V. Description of the invention (21) " ~ Amphoteric glycine, phospholipid ethanolamine, cysteamine sulfinic acid, chitosan, amphoteric inorganic oxide, polyamidoamine, dendrimer based on polyamidoamine Sodium hydroxymethyl glycinate and polyethylene diamine. The utilization rate and mildness of the topical composition of the present invention can also be enhanced by certain integrators, and its concentration is about 0.01 to 25 weight percent, preferably about 10 weight percent, and the best addition is about i to about 5%. . Examples of suitable chelating agents include those with a high affinity for substances such as: rhenium, iron, or iron and / or copper ion, such as: ethylenediaminetetraacetic acid, ethylenedioxy · diethylethyl-diazine -Tetraacetic acid, salicylaldehyde, quinolinol, diaminocyclohexane_tetraacetic acid, diethylethyltriamine-pentaacetic acid, dimethylethylenedioxime, amine benzooxime, triethylene glycol Ethyltetramine, desferoxamine, or mixtures thereof. The invention also includes methods of treating the aforementioned skin conditions with these compounds. These methods include topically applying an effective amount of one or more compounds of formula (1) to the affected part of the skin, usually once or twice a day. These methods also include the second application to a physiologically acceptable excipient containing an effective amount of one or more compounds of formula (1) to the affected part of the skin, usually once or twice a day. When at ambient temperature, these compounds are liquid (eg 3,6, ^ trioxaundecadecanedioic acid) 'and when using oxygen-containing compounds, for example ... for skin scrub or softening hair' method of the present invention This includes topical application of a compound of formula (worker) to a concentration of 100%. The following examples illustrate the invention without limiting it. t_ The composition of the present invention is generally formulated as a lotion, cream or gel for topical application. Example 1 _ -24- This paper size is applicable to China National Standard (CNS) A4 (21GX297). -------- ^ batch ------ 1T ------ (please first Read the notes on the back and fill in this page) Printed by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs 580493 A7 ____ B7 _____ V. Description of the invention (22) Preparation method of a topical compound of glyoxalic acid In an appropriate container, add water, Glycerin, propylene glycol, Na2EDTA and trioxaundecanoic acid were mixed together. Add ammonium hydroxide to this container gradually to adjust the pH to a desired range. After this adjustment step of acid-base rhenium, it is heated to 170 to 175. F. Add a few ethylcellulose and stir until homogeneous. Phase A is complete. For lotions and creams, add Phase B to the appropriate second container, mix and heat to 170 to 175 QF. Then, stage B is fully mixed with stage a and reheated to 170 to 175. F. The batch was then cooled to 120 QF. Add stage C to the batch and mix well. Stage 0 gel wash solution (A) water QSQSQs glycerin 5.00 3.00 5. 〇〇 'propylene glycol 3.00 3.00 3.00 EDTA disodium 0.10 0.10 0.10 3,6,9-trioxane Eleven 10.00 10.00 10.00 Hydroxanthylcellulose 0.50 0.30 0.50 Ammonium hydroxide (30%) to acid test to acid base to acid base 3.7-3.9 3.7-3.9 3.7-3.9 (B) Brown shelf Octyl Ester-3.00 5.00 Myristyl Myristate-3.00 5.00 • Glyceryl Monostearate-1.50 3.00 Cetyl Stearyl Alcohol and-3.00 CETEARETH-20 -25- This paper size applies to Chinese National Standard (CNS) A4 (210X297 mm) -------- 0 ^ ------ 1T ------ 9 (Read the precautions on the back before filling this page) 580493 A7 B7 V. Description of the invention ( 23) Methyl paraoxobenzoate (C) imidazolidine | monthly exhibition 0.3 0 0.20 0.30 0.20 0.30 Printed by the Consumers' Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs All figures are expressed as a percentage of the total weight of the composition. Except for the range of Q and S supplemented with water. After explaining all the advantages of the present invention, those skilled in the art will understand other carriers besides lotions, creams or gels. The normalization of microscopic exfoliation of the stratum corneum or macroscopic epidermis is a prerequisite for the design of this oxygenated acid compound and composition to alleviate skin disorders. The following examples specifically illustrate the superior exfoliating activity provided by the oxydiacid composition. Example 2 Peeling patch test for peeling activity Generally, the I 'peeling patch test method is applied to the skin for 24 hours. The skin was graded immediately and the patch was removed after 24 hours. The primary focus of this test is on the effect of the product on the stratum corneum and mainly on the exfoliation effect. After 24 hours of visual appraisal after the patch was applied, the exfoliating fine activity sampling (CRAS) was performed. The CRAS score was the amount of keratinocyte exfoliation, and the calculation method was based on the amount of keratinocytes removed per sample. A series of studies were carried out. The evaluation of the exfoliation within one day (CRAS) showed that the exfoliation activity ratio of 10,6% by weight 3,9_trioxaundecanedicarboxylic acid composition at pH 3.7 Acid-base 値 38, containing 4% by weight glycolic acid, the formulation is more superior. This study explored 10% by weight of oxo diacid under low and high acid-base 値 and 5% by weight of oxo diacid Tribal characteristics under low acid and alkali conditions. The 4 wt% glycolic acid is used as a reference substance. The following table j is cellodine -------- threat clothing-(Read the precautions on the back before filling This page) Order 26 paper standards (CNS) A4 size (210X297 mm) 580493 A7 B7 V. Description of invention (24) Complete comprehensive information and material description. Table 1 pH CRAS 5 wt% oxygen-containing two Acid 3.7 2.58 1 0% by weight of oxydiacid 3.7 2.93 1 0% by weight of oxydiacid 5.4 2.68 4% by weight % Glycolic acid 3.8 2.80 No obvious irritation response was observed in any of the samples. All the various comparisons, 10% oxygen in the low acid test-the sample is consistently better and-丨 ^ ------ -— (Please read the notes on the back before filling out this page) The printed table produced by the Consumer Cooperatives of the Central Bureau of Standards of the Ministry of Economic Affairs has significantly better peeling activity. The next study in this series is to confirm the content with 0% by weight 3, 6,9_trioxaundecanedicarboxylic acid composition has better exfoliating activity than 4% by weight glycolic acid formulation. At the same time, the 3,6,9_trioxaundecanedicarboxylic acid composition It is milder on the skin compared to 4% by weight glycolic acid. It should be noted that 10% of the 3,6,9-dioxaundecane diacid composition has a low "acid" concentration (in moles) "Acid," concentration in a 4% glycolic acid formulation. In conjunction with the clinical results of this article, it is shown that the exfoliation effect of 3,6,9 · trioxaundecanedicarboxylic acid is significantly higher than that of glycolic acid. The second study was to confirm the results observed for a 10% oxygenated diacid composition at pH 3 · 7. Table 2 below is the comprehensive data and material description of the second study. -27- The size of this paper is suitable • Chinese national standard (CNXJT ^ format (210X297) ^ 7, -port 580493 A7 B7 V. Description of the invention (25) A_ pH PII 3.7 0.13 3.74 0.18 7 0.23 CRAS 3.23 3.33.05 Previous CRAS 2.93 1% by weight of oxo diacid 10% by weight of oxo diacid No obvious stimulus response was observed in all the tested samples, but the use of 使用 'oxo diacid did provide compared with acetic acid and vehicle Lower irritation index (PI). This result confirms what was observed with the exfoliation analysis method of Example 2. $ Example 3 Cream for Highly Pigmented Spots This example illustrates preparation and is used to reduce the appearance of highly pigmented spots on the skin of hands. Cracking-(Please read the notes on the back before filling out this page),-Isopropyl myristate printed by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs, W / W% 3.0 Propanediol (1 000 ) Monostearic acid 5.0 Palmitic acid 10.0 3,6,9,12_ Tetraoxadodecanedicarboxylic acid 100 Glycerin 3.0 Polyethylene glycol (3 00) Monostearic acid 5.0 Paramethylbenzoate 0.2 Resistance Scurvy-based scales: acid money 2.0 water 60.0 spices and pigments to 10.0 · triethanol Amine to acid-base 値 4.0 -28 This paper size applies Chinese National Standard (CNS) A4 specification (210X297 mm) Φ 580493 580493 W / W% 2.0 1.0. Lanolin is soluble in sunflower oil or soybean oil cyclomethyl silicone oil Rose block extract stage B sodium iodide 3,6,9-trioxaundecylide diacid kl 5. Description of the invention (26) All figures are expressed as a percentage of the total weight of the composition, and the acid and alkali are eliminated 4. Example 4. Cream for ichthyosis and skin hyperkeratinization_ This example illustrates a silicone cream prepared according to the present invention and used to treat dry skin, ichthyosis, and hyperkeratinization.

Phase A lauryl methyl silicone copolyol mineral oil 10.0 6.0 2.0 2.0 9.0 3,6,9,12,15-pentaoxaheptadecanedioic acid 1.0 sodium methylol glycine 0 5 Mineral water to 100.0

AIL-based glycine sodium _ to acid and base 13 S 29- This paper is suitable for use and used in Zhongguanjia Standard (CNS) A4 size (21Qx 297) (Please read the precautions on the back and save this page)- · All figures printed by the Consumers' Cooperatives of the Central Bureau of Standards of the Ministry of Economic Affairs are expressed as a percentage of the total weight of the composition, with the exception of acids and alkalis. 580493 kl V. Description of the Invention (27) Example 5 Silicone This example illustrates a water-in-silicone gel composition. Stage AW / W% Dimethicone 10.0 Dimethicone Copolyol 10.0 Cyclomethylsilicone 5.0 Stage B 3,6,9-trioxaundecadecanedioic acid 8.0 Glycerol 20. 〇 Demineralized water to 100.0 Triethanolamine to acid-base 値 4. 〇 --------- · «.! (Please read the notes on the back before filling out this page. J Consumer Cooperatives, Central Standards Bureau, Ministry of Economic Affairs Print

All figures are given as a percentage of the total weight of the composition. Example 6 Milk for Acne, Skin Spots, and Age Spots This example illustrates the milk stage AW / W% for treating Acne, Skin spots, and Age spots. Oleic acid 1.0 Stearic acid 17.0 • Polyoxyethylene (2 propylene glycol Monostearate) 10.0 Retinol 0.1 Phase B Acid Test-Order 4 I-1-- II ......... -30- This paper size applies to China National Standard (CNS) A4 (210X297 mm 580493 kl B7 five 'invention description (28.0 0 glycerol 2 · pyrrolidone-5-carboxylic acid 3,6,9-trioxa ^^ monocarboxedioic acid 7.5 3,6,9,12 -Tetraoxatetradecanedioic acid 2.5 Lactic acid 3.0 Demineralized water to 100.0 Oxidation according to _ to acid test 4.2 All figures are expressed as a percentage of the total weight of the composition, except for acid and alkali hydrazone. According to this disclosure Summary of the text 'to make various amendments and changes to the present invention. Such changes and additions must be within the scope and spirit of the present invention as defined by the following patent application parks. (Please read the precautions on the back before filling out this page) Printed by the Employees' Cooperative of the Central Bureau of Standards of the Ministry of Economic Affairs 3 This paper is sized for China National Standard (CNS) A4 210X 297 mm) I

Claims (1)

580493 A8 B8 C8 D8 Patent Application No. 0871〇672〇 Chinese Patent Application Replacement (January 1993) " " ", Chinese-Please-Patent Advisor; Bulletin, 1 ···· / 一 f I 1. A topical group β Α person for treating skin disorders caused by, or accompanied by the appearance of, or exacerbation of abnormal peeling effects caused by 屮 1 目 ~ Ύ, ~~ ^, —J — τ 咚3, composition for I, comprising an appropriate topical carrier and a compound of formula (I): Where R4 is (CRsRfCF ^ Rs-X ^ .ci ^ upXdXAn, η is an integer from 2 to 12; Ri, r2, r6, R7, r8, R9, R10, and Rw are hydrogen; and χ, χ, χ2, χ3, y, and 2 are independently 0, and the composition includes 0.1 to 95% by weight of the compound of formula (I) and the acid-base value is less than 7.0. 2. The composition according to item 1 of the patent application scope, wherein The compound of formula (I) accounts for 1 to 50 weight percent of the composition. 3. The composition according to item 2 of the patent application scope, wherein the compound of formula (I) accounts for 5 to 20 weight percent of the composition. The composition of the scope of patent application item 1, which also includes a mixture containing at least two different compounds of formula (I). 5. The composition of the scope of patent application item 1, wherein the compound is selected from: 3, 6-2 Oxaoctanedioic acid, 3,6,9-trioxaundecanedicarboxylic acid, 3,6,9,12-tetraoxatetradecanedioic acid, 3,6,9,12,15 -Pentahexadecane dicarboxylic acid, 2-methyl-3,6,9 -trioxazone, carbon diacid, O: \ 52 \ 52969-930130.DOC 5 " * " This paper size applies to Chinese National Standard (CNS) A4 specification (210X297 mm) 580493 Patent application scope A8 Βδ C8 D8 ---- ^ 2 -ethyl-3,6,9,12 -Siwei Weishan ten-carbon Burned diacid diethylene twentieth: = diacid ~ trioxacarbon diacid, and mixtures thereof. , ° _dimethyl_3,6,9 'trigas hetero 10-6 · t apply the composition of item 1 wherein the carrier is selected from the group consisting of 冼 night, cream and gel. , K since ···: The composition of the scope of application for item i, which also includes the favorite: Actives: Fungicides, Vitamins: Allergens, Decolorants, Anti-inflammatory Agents, Anesthetics, == Bu Wet ratio agent, peeling agent, emulsifier, stabilizer, preservative, anti-xiao training, softener, thickener, lubricant, humectant, chelating agent, perfume, #color agent and skin penetration enhancer. 8. If the composition of the scope of application for the patent application item i, the acid test value in the "" to 7 0. 9. The composition of the scope of the application for the patent application item 8, wherein the pH value is 3.5 to 4 〇10. The composition of claim 1 includes a compound of formula (I) in an amount of 0.1 to 95 weight percent; a softener in an amount of 0.5 to 50 weight percent and an emulsifier in an amount of qi to 30 weight percent. The composition of the scope of the application for patent, wherein the compound is selected from the group consisting of 3,6-dioxaoctanoic acid, 3,6,9-trioxaundecyrate, 3,6, 9,12 -tetraoxatetradecanedioic acid, 3,6,9,12,15 -pentaoxatetradecanedioic acid; and wherein the softener is selected from the group consisting of mineral oil, petrolatum, paraffin Oil, kerosene, cactus oil, paraffin wax, microcrystalline wax, perhydrosqualene 'dimethyl polysiloxane-2-O: \ 52 \ 52969-930130.DOC 5 This paper size applies to Chinese National Standard (CNS) A4 Specifications (210X297 mm) 580493 A8 B8 C8 __ ___D8__ VI. Patent application Fanyuanyao, f phenyl polysiloxane, silicone diol copolymer, triglyceride, acetolated monoglyceride, ethyl acetate Glycerides, alkyl esters of fatty acids, fatty acids and alcohols, lanolin and lanolin derivatives, polyalcohol esters, sterols, beeswax derivatives, polyhydric alcohols and polyethers and amines of fatty acids, and among these emulsifiers It is selected from the group consisting of: sorbitan anhydride, alkoxylated fatty alcohols, alkyl I sugar sweeteners, fertility, tigeryl sulfate, mono- and di-alkyl phosphoric acid, sulfonium alkylsulfonate, and fluorenyl isothiocarbonyl. 12. The composition according to item 1 of the scope of patent application, wherein the composition is in a form selected from the group consisting of oil-in-water emulsion, water-in-oil emulsion, water-oil_water-based emulsion and oil-water-silicone A ketone liquid emulsion. 13. The composition according to item 6 of the patent application, wherein the topical carrier comprises a component selected from the group consisting of ammonium hydroxide, ceteary 1 alcohol / Ceteareth-20, EDTA, glycerin Glyceryl monostearate, isoethylcellulose, imidazolidinyl urea, methyl paraoxybenzoate, myristyl myristate, octyl palmitate, and propylene glycol and mixtures thereof. The composition of item 12, wherein the carrier comprises: ( a) 2 weight percent to 10 weight percent glycerol; (b) 1 weight percent to 10 weight percent propylene glycol; (c) 0.1 weight percent to 2 weight percent ethyl cellulose; (d) Ol weight percent to 1% by weight of imidazolidinyl urea; (e) 0.01% by weight to 2% by weight of EDTA; and the pH value of the composition is less than 7.0. 15. If the composition of the 12th item of the patent application, The carrier includes: O: \ 52 \ 52969-930130.DOC 5 " 3 580493 A8 B8 C8 D8 VI. Patent application scope ^ (a) 1 to 10 weight percent glycerin; (b) 1 to 10 weight percent propylene glycol; (c) 1 to 10 weight percent palm Caprylic acid; (d) 1 to 10 weight percent of myristyl myristate; (e) 1 to 6 weight percent of cetearethanol / Ceteareth-20; (f) 0 to 5 weight Percent to 6 weight percent of glyceryl monostearate; (g) 0.1 to 2 weight percent of hydroxyethylcellulose; (h) 0 to 1 to 1 weight percent of miquatyl urea; About 0.05 to 0.5 weight percent of methyl paraoxybenzoate; (j) 0.01 to 2 weight percent of EDTA second steel, and the acid test value of the composition is less than 7.0. 16. The composition according to item 12 of the patent application range, wherein the carrier comprises: (a) 2 weight percent to about 10 weight percent glycerol; (b) 1 weight percent to about 10 weight percent palmitic acid palmitate Indications; (c) 1% by weight to about 10% by weight of myristic acid myristyl, (d) 1% to 7% by weight of cetyl stearyl alcohol / Ceteareth-20; (e) 1 weight Percent to 10% by weight of propylene glycol; -4-O: \ 52 \ 52969-930130.DOC 5 This paper size applies to China National Standard (CNS) A4 specifications (210 X 297 mm) 580493 8 8 8 8 A BCD 々, Patent application range (f) 1 to 6 weight percent glyceryl monostearate; (g) 0 · 1 to 2 weight percent of hydroxyethyl cellulose; (h) 0.1 to 1 weight percent (I) 0.05 wt% to 0.5 wt% of methyl paraoxybenzoate; (j) 0.01 wt% to 2 wt% disodium EDTA, and the pH value of the composition is less than 7.0 . O: \ 52 \ 52969-930L30.DOC 5 ~ 5 This paper size applies to China National Standard (CNS) A4 (210 X 297 mm)