TW389693B - Pharmaceutical composition for inhibiting skin and vagina atrophy - Google Patents

Description

A7 B7 Printed by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs 5. Description of the invention ()) It is widely known that the appearance and texture of the skin will change with age. This subject is subjective in terms of personal assessment and basic impressions. In general, the general atrophy of aging skin concerns has an effect on cosmetics' but may have pathological effects, many of which are intrinsically psychological effects that become "old" feelings, depression, and loss of sexual appeal. In some cases, atrophy of the skin of older persons may be directly related to the disease such as the ability of the skin to repair in the treatment of injuries. In general, atrophy of the skin is regarded as the result of gradual aging and is regarded as a “gift of good”. Although aging is generally acceptable, women _ still have menopause for a certain period of time in life. Progressive aging horizontal, especially the vagina and atrophy are quite rapid. Often this rapid and sudden change can lead to frustration of the lesion and the heart. In addition, vaginal atrophy may be uncomfortable, such as itching, dryness, and pain during intercourse. Sexual pleasure is lost. Harmony with couples and in some cases, social causes such as divorce. As mentioned above, atrophy or aging of the pimples may have a qualitative and quantitative perspective. From a qualitative point of view: changes in smoothness and texture cause the skin to feel a "rough" feel. * The elasticity of the skin changes, so the mechanical properties of skin care and skin care pigment 2 change. Common conditions for these qualitative changes to cause atrophy of skin and skin are cramping and rashes. From the perspective of quantity, the aging of women's skin after menopause can be measured: mitosis of keratinocytes slows down, and changes in the thickness of skin cells' reduced glucosamine polysaccharides and soluble collagen. The wetting content is related to the decrease in urinary excretion of hydroxyproline (a measure of the decrease in collagen weight). The change in the quality of the skin and the changes in the blindness and mechanical properties is the loss of external cellular matrix components. Or change. Therefore, it may be possible to evaluate the benefits of post-menopausal atrophic skin atrophy therapy. -4- This paper size applies to China National Standard (CNS) A4g (210X297 mm) (Please read the precautions on the back before filling out this page) -I pack Ordering-A7 B7 Printed by the Consumer Cooperatives of the Central Bureau of Standards of the Ministry of Economic Affairs. 5. Description of Invention (2) The role cannot be completely dependent on subjective analysis, even if subjective improvement may be the basic required effect. In the case of vaginal Tsai contraction, the amount is the amount of vaginal wetting, which is controlled by the amount of glandular secretion in the dermis, and the result is subjective comfort. There are currently two main therapies that can be used to treat the skin of postmenopausal women. Concerns and vaginal atrophy. The first treatment is a makeup method such as using makeup, moisturizer, night cream, vaginal lubricant, etc. Although this cosmetic treatment does not affect the previous physiological cause of atrophy, the method is often subjective to the individual. The second type of therapy involves the treatment of previous physiological causes with active, pharmaceuticals (most notably vitamin A and estrogen). The efficacy of vitamin A is controversial and it is known to have substantial unwanted side effects, limiting its use. During menopause, the ovarian hormone production of hormonal content decreases rapidly. Estrogen slippage has far-reaching effects on the skin and vagina, causing the natural atrophy process to rapidly increase. Estrogen replacement therapy is often used to treat skin anxiety and vaginal atrophy. However, estrogen replacement therapy has unwanted side effects, and the most serious side effects are likely to cause cancer. Agents containing corpus luteum can have undesired psychological effects. For the purpose of treating skin and vaginal atrophy alone, the common cause of estrogen replacement therapy is side effects. Obviously, effective and safe agents that have a positive effect on previous physiology and improve post-menopausal women's skin and vaginal properties will be useful. The method of the present invention provides a method for inhibiting skin atrophy or vaginal atrophy, which comprises administering an effective minimum compound of the formula 丨 to a person who needs the 5-size of this paper applies the Chinese National Standard (CNS) A4 specification (210X 297 mm) ( Please read the precautions on the back before filling in this page), | install ·-° Printed by the Consumers' Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs A7 --- --B7 V. Description of the invention (3)

0 gan + 1 丨 where and R3 are hydrogen, -CH3, -C-(Ci-Ce alkyl), or 0

II ~ c-A r, where A Γ · is any substituted phenyl group; R2 is borrowed from pyrrolidinyl, hexamethyleneimine, and N-hexahydropyridyl; and it is pharmaceutically acceptable Salts and solvates. The present invention has discovered that the selective radical of 2-phenyl-3-arylfluorenylbenzylthiopan in the benzothiophenes of formula I can inhibit skin or vaginal atrophy. The method of treating the present invention is to administer to a person in need a dose of a compound of formula I or a peony acceptable salt or solvate thereof which is effective in inhibiting cutaneous or vaginal atrophy. The term suppression generally accepts patients whose definitions include preventive treatment of the above-mentioned conditions, stopping and / or treating existing conditions. The invention is intended to include medical treatment and / or prophylactic treatment. Raloxifene, a compound of the invention (wherein the hydrochloride of the compound of formula I, R1 and R3 are hydrogen and R2 is hexahydropyridyl). It is a nuclear regulatory molecule. B shows that Rosifen is bound to the hormonal receptor and was originally thought to be a drug. The arsenic function is a peptidyl hormone-activated organelle and an anti-hormonal molecule that depends on estrogen. Breast cancer. In fact, Rosifin can indeed block hormonal hormones. -6- This paper size applies the Chinese National Standard (CNS) A4 specification (210X297 mm) —S — ^ ------ Order —-----} line (Please read the notes on the back before filling this page) A7 B7

Employees' Cooperatives of the Central Bureau of Standards of the Ministry of Economic Affairs of the People's Republic of China I. 5. Description of the Invention (4) Some _ fine effects, however, in other cell types, Rosifen activates the same genes as estrogen and exhibits the same pharmacological effects, such as bone Looseness and hyperlipidemia. As a result, Rosifen was considered an anti-hormone with a mixed agonist and antagonist properties. Rosifen exhibits properties different from hormonal hormones and is now thought to be due to the specific activation and / or inhibition of different groups due to the activation and / or inhibition of genes by the Rosifen-estrogen receptor complex. Its function. Therefore, although rosoxifen and estrogen use the same receptor as the competition, the pharmacological results of these two gene regulation are not easily predictable and specific to each other. Rosifen and similar analogs are safe and effective agents, which have a positive effect on previous physiological_b mechanisms seen in cutaneous anxiety and vaginal atrophy. The positive effect of Rosifen and the use of analogues is the improvement of dermatological and vaginal quality characteristics. This compound is generally formulated and squeezed into excipients, diluents or carriers and compressed into tablets, or formulated into tinctures or solutions. To facilitate oral axillary, intramuscular or intravenous administration. The compound can be administered transdermally and can be formulated into a sustained release dosage form. The method of the present invention can be manufactured according to the level of detail of established procedures such as U.S. patents 4, 1 3 3, 8 1 4 '4, 41 δ, 0 6 and 4. 8 0, 05 (also incorporated herein by reference). The compound used. Generally, this method is initiated with 6-hydroxy and 2- (4-hydroxyphenyl) benzo [b 1thiophene. The starting compounds are protected, tritiated and deprotected to form compounds of formula I. Examples of the preparation of this compound are the US threshold patents discussed above. Any substituted phenyl includes phenyl and ~ or secondary alkyl, C, -C 4 alkanoyl, hydroxyl, nitro, ammonium, fluorine, or tri-7- This paper size applies to Chinese National Standard (CNS) A4 Specifications (21 0X 2M mm) (Please read the precautions on the back before filling out this page) τ Assembling and Printing Printed by the Consumers' Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs A7 _____B7_________ V. Invention Description (5) (F) Benzoyl substituted by formamidine. The compound M used in the method of the present invention forms a wide range of organic and inorganic acids and bases to form pharmaceutically acceptable acid and base addition salts and includes physiologically acceptable salts commonly used in the pharmaceutical industry. This salt is also part of the invention. Typical inorganic acids used to form this salt include hydrochloric acid, hydrobromic acid, hydroiodic acid, nitric acid, sulfuric acid, phosphoric acid, low-disc acid, and the like. Salts derived from organic acids such as aliphatic mono- and dicarboxylic acids, phenyl-substituted alkanoic acids, hydroxyalkanoic acids and hydroxyalkanedicarboxylic acids, aromatic acids, fats, and aromatic sulfonic acids can also be used. Acceptable salts of this peony include acetate, phenylacetate, trichloroacetate, acrylate, ascorbate, benzoate, chlorobenzoate, dinitrobenzoate, hydroxybenzene Formate, methoxybenzoate, methylbenzate, o-ethoxybenzoate, naphthalene-2 -benzoate, bromide, isobutyrate, benzylbutyrate Salt, Ling-Hydroxybutyrate, Butyne-U4-Diacid, Hexyne-1,4-Diacid, Decanoate, Rhenium Caprylate, Aromatate, Cinnamate, Citrate, Formate , Fumarate salt, glycolate, heptanoate, hippurate, 'lactate, malate, maleate, hydroxymaleate, malonate, bitter almond, Mesylate, nicotinate, isonicotinate, nitrate, oxalate, phthalate, paraben, phosphate, monohydrogen phosphate, dihydrogen phosphate , Metaphosphate, pyrophosphate, propionate, propionate, phenylpropionate, salicylate, sebacate, succinate, caprylate. Lanthanum diacid, tellurate, hydrogen sulfate Salt, pyrosulfate Tellurite, bisulfite, sulfonate, benzylsulfonate, p-bromobenzylsulfonate, chlorobenzylsulfonium, lanthanum ethanesulfonate, 2-hydroxyethanesulfonate, methanesulfonic acid Salt, lanthanum naphthalene-1-sulfonate, lanthanum naphthalene-2-sulfonate, p-toluenesulfonate, xylene sulfonate, wine-8-This paper size applies to China National Standard (CNS) A4 specification (210 × 297 (Mm) (Please read the notes on the back before filling out this page). Packing, 1T printed by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs A7 _________._ B7 V. Description of the invention (6) Hemate salts, etc. Preferable salt is pseudohydrochloride. Pharmaceutically acceptable acid addition salts are typically formed by reacting a compound of formula I with an isomolar or peracid. The reactants are typically bound to a mutual solvent such as diethyl ether or benzene.鞔 Generally, it is allowed to sink in solution from 1 hour to 10 days and can be separated by filtration or the solvent can be stripped in a conventional manner. The bases typically used to form salts include ammonium hydroxide, nitrogen oxides of alkali metals and alkaline earth metals, carbonate K and aliphatic and primary amines, secondary and tertiary amines, and aliphatic diamines. Particularly good bases for the preparation of addition salts include hydroxide, saddle, potassium carbonate, methylamine, diethylamine, ethylenediamine and cyclohexylamine. Compared with their derivative compounds, peony acceptable salts generally have increased solubility characteristics and are therefore often formulated into liquids or emulsions. Peony compositions can be prepared by procedures known in the art. For example, compounds can be formulated with general pears, diluents or carriers to form lozenges, capsules, suspensions, powders and the like. Examples of excipients, diluents and carriers suitable for this composition include the following: fillers and fillers such as starch, sugar, mannitol and silicic acid derivatives; binders such as carboxymethyl cellulose and other fibers Derivatives, alginates, gelatin, and polyvinylpyrrolidone; wetting agents such as glycerol; disintegrants such as calcium carbonate and sodium bicarbonate, slowing dissolving agents such as bond alkanes; promoting absorption agents such as quaternary ammonium compounds; interfaces Active agents such as cetyl alcohol, glycerol monostearic acid absorbing carriers such as kaolin and pulp, and lubricants such as talc, calcium stearate and magnesium, and solid polyethylene glycols. The compounds can also be formulated as elixirs or solutions (solutions suitable for oral and axillary administration or suitable for parenteral administration (such as intramuscular, subcutaneous or intravenous routes). In addition, the compounds are formulated into sustained release dosage forms and the like. Therefore, the sister compound can be composed of a section of -9- This paper applies the Chinese National Standard (CNS) A4 specification (210 × 297 mm) ——I- (Please read the precautions on the back before filling in this page) Γ λ ^ / ί, mn ^ i ^ ^ 1 ^ 1 ^ 1 Km · m · — ^^^^ 1 ^^^^ 1 In ffi ^^ i ^^^^ 1 · ^ _ Printed by the Staff Consumer Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs Preparation of A7 B7 V. Description of the invention (7) During the period of time, it may be better to release active ingredients in specific parts of the intestine. For example, coatings, coatings and protective substrates can be made from polymeric substances or waxes. The particular dose of the compound of formula I according to the invention, which is required to inhibit dermatitis or vaginal atrophy, is determined by the caregiver depending on the severity of the condition, the route of administration and related factors. Generally, an accepted and effective daily dose is from about 0.1 to about 1000 mg / day, and monthly menstrual teeth are about 50 to about 200 mg / day. This dose can be administered to the subject to be treated 1 to about 3 times a day, or as many times as needed to treat the subject. _ For administration to the palate, this compound can be formulated by known techniques and applied directly to the area of effect. Formerly known forms for this purpose include soft lotions, lotions, pastes, gels, mists and aerosols. The weight percentage of the composition of the present invention in the topical composition depends on different factors, but the general form accounts for 0.5% to 95% of the total weight of the composition, typically 1 to 25% by weight. These compositions may take the form of aqueous or non-aqueous solutions or dispersants, or they may be in the form of a milk surface or suspension. These compounds may contain pharmaceutically acceptable vehicles and adjuvants known in the art. Where possible, for example, one or more organic solvents are used to prepare the solution. These solvents are physiologically acceptable and selected from (in addition to water) such as propionate, ethyl acetate, isopropyl alcohol, glyceryl ether. The product names sold are "Dowanol", polyglycols and polyethylene glycols, Ci-Cd alkyl esters of short-chain acids, preferably ethyl lactate or isopropyl glutamate, and fatty acid triglycerides such as Livestock products on the market named "M ii? 1 y 〇1", isopropyl myristate, animal oil, mineral oil and vegetable oil, and polysilicon. Air sweep. The composition of the present invention may also contain a thickener Such as cellulose and / or cellulose derivative-10- This paper size applies to China National Standard (CNS) A4 specification (210X297 mm) (Please read the precautions on the back before filling this page)-Binding · Binding-

A B V. Description of the invention (8) Biology. They may contain, for example, yellow gum, sial gum or Carob gum or gum arabic or polyethylene glycol, bentonites and montmorillonite (m ο ntm 〇r Π 1 ο η ί t · es )Wait. If necessary, an adjuvant selected from antioxidants, surfactants, other preservatives, film-forming agents, keratolytic agents or acne agents, perfumes and colorants can be added. Examples of oxidizing agents such as tertiary butyl hydroquinone, butyl Hydrated hydroxymethoxybenzene, butylated hydroxytoluene and α-tocopherol, and possible derivatives thereof. Mainly used for the preparation of topical galenical preparations such as milk buds, milk, gels, dispersants or microemulsions, more or less thick lotions, impact resistant pads, soft or patch forms, or Jit gas In the form of a sol (spray) or foam or in the form of a soap cake. In the following compositions, "active ingredient" means a compound of formula I. Combination ..., .....: .. Ming capsules use the following to prepare hard shell Ming capsules: (Please read the precautions on the back before filling this page) Printed by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs (mg) / Capsule) Active ingredient 0.1-1000 Starch NF 0-6.5 0 Starch flowable powder 0-6 5 0 Siloxane solution 350 centimeters 0-15 -11- This paper size applies to China National Standard (CNS) A4 specifications ( 210X297 mm) 5. Description of the invention (9) A7 B7 mixed ingredients, passed through a No. 45 mesh US sieve, and filled into a hard shell capsule. An example of a specific capsule composition of raloxifene has been manufactured and includes the following: Group ϋΐ: Rosifen capsule content (mg / capsule) Rosifen starch, HF starch flowable powder siloxane solution 3 5 0% 112 2 2 5.3 1 compound _3: Rosifen capsule content (mg / capsule) (Please read the precautions on the back before filling out this page) i. Order the Rosifen starch printed by the Consumer Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs, NF Starch flowable powder oxane solution 3 5 0 box history 5 108 2 2 5.3: line 12 This paper size is applicable to Chinese National Standard (CNS) A4 specification (210X 297 mm) 5. Description of the invention (1〇) A7 B7 Combination .. Object_Left: Rosifen capsule ingredients for children (mg / capsule) Rosifen 10 starch, HF 103 Starch flowable powder 225.3 Silane solution 3 5 0% history 1.7 (Please read the precautions on the back before filling the nest This page). Composition. 5 .: Rosifen capsule content (mg / capsule) Rosifen 50 starch, NF 150 starch flowable powder 397 Silicone solution 3 50% history 3 Member of the Central Standards Bureau of the Ministry of Economic Affairs The specific compound printed by the consumer cooperative can be changed according to the reasonable changes provided. The tablet composition is prepared with the following ingredients: D > '). · ^ -M · m ^ i ^^^^ 1 —mV —Am mu ^^^^ 1 v ^ i ^ — -5 issues_ -13- This paper size applies to China National Standard (CNS) A4 specifications (210 X 297 mm) A7 B7 V. Description of the invention (centrally by the Ministry of Economic Affairs) Standard Bureau employee consumer cooperative printed composition 1: Lozenge ingredient amount (mg / lozenge) Active ingredient 0.1-1000 Microcrystalline cellulose 0-650 Fuming silica 2-0-650 Stearic acid 0-15 Mixed each Ingredients and squeezed into tablets. In addition, each tablet containing 0.1 mg to 100 mg & sexual ingredients is prepared as follows: Group_Composition_ 物 7 ..: i Lozenges) Active Ingredients 0.1-1000 Starch 45 Microcrystalline Cellulose 35 Polyvinylpyrrolidine hydrazone 4 (such as a 10% solution in water) Carboxymethyl Cellulose Sodium 4.5 Magnesium Stearate 0.5 Talc 1 " 1 4- (Please read the notes on the back before filling in this page.) D Jn ml nn —HI— · 111 < ^ _ m · m · -— Thread --- This paper ruler Applicable to China National Standard (CNS) A4 specifications (210X297 mm) A7 B7 V. Description of the invention (12) The ingredients, starch and cellulose of the work piece are passed through a 45 mesh US sieve and fully mixed. The resulting powder was mixed with a solution of polyvinylpyridone and passed through a No. 14 mesh US sieve. The granulation was dried at 50 ° -60P and passed through a No. 18 mesh US sieve. First, sodium carboxymethyl cellulose, magnesium stearate and talc are passed through a No. 60 US sieve, then granules are added, and after mixing, they are squeezed in a tablet machine to produce tablets. Each suspension containing 0.1-1000 mg of each drug in a 5 ml dose is prepared as follows: Group: combined IJI: amount of suspension ingredients (mg / 5 ml) active ingredient Q. 1-1000 mg carboxymethyl Cellulose sodium 50 mg syrup 1.2 5 g grams of cage formic acid solution 0. 10 ml of flavoring agent required amount of toner pure water to 5 ml ---.------ (Please read the precautions on the back first (Fill in this page again.) 'Printed by the Consumer Cooperatives of the Central Bureau of Standards of the Ministry of Line Economy. The product passed through a 45 mesh US sieve and was mixed with carboxymethyl cellulose sodium and syrup to form a smooth paste. Dilute the benzoic acid solution, flavoring agent and coloring agent with some water and mix back. Sufficient water is then added to make the desired volume. Preparation of the following composition: -15- This paper size applies Chinese National Standard (CNS) A4 specification (210 X297 mm) A7 B7 V. Description of the invention (13) Combination ._ 物 _. .9 .. Ingredients (mg / 5ml) hydroxypropyl cellulose active ingredient isopropyl alcohol qs 1.5 grams 5-30 grams 100 grams sister HI-Q- II (Please read the precautions on the back before filling this page) • Packing. Ingredients (mg / 5 ml)

Active ingredients of hydroxypropyl cellulose ethyl acetate isopropyl alcohol dS 1 · 5 g 15.0 g 5-30 g 100 g 'printed by the Central Consumers Bureau of the Ministry of Economic Affairs Consumer Cooperatives -16 This paper size applies to Chinese National Standards (CNS) A4 specifications (210X297 mm) A7 B7 V. Description of the invention (14 groups. Saturated_ υ. Ingredients (mg / 5 奄 L) Hydroxypropyl cellulose 1.0 g Butyl hydroxytoluene 0.02 g Active ingredient 1.5-25 Gram ethanol q S 100 grams (please read the precautions on the back before filling out this page) -I pack. Group ... Composition ... 丄 2_ Ingredients (mg / 5ml) Order hydroxypropyl cellulose 1.5 g of butyl. Hydroxytoluene 0.01 g C s -C 1 2 m fatty acid triglyceride 10.0 g active ingredient 1.5-30 g isopropanol qs 100 g line Molybdenum printed by the Ministry of Economic Affairs Central Standards Bureau Consumer Consumption Cooperative Compound 9-1 2 is in the form of a gel 17- This paper size applies the Chinese National Standard (CNS) A4 specification (210X29? Mm) A7 B7 V. Description of the invention (V5) Combination ._ 物 .._ 1..3_ Ingredients (mg / 5 ml) isopropanol. 46.0 g active Servings' 1.0- 15 grams of Cs 2 fatty acid triglycerides 49.0 grams of group-He-Huang Huang 4-Ingredients ^ (mg / 5ml) (Please read the precautions on the back before filling out this page)-Pack Ethyl acetate active ingredient (: «-(^ 2 fatty acid triglyceride 69.0 g 10, 0 g 5-20 g 3 0.0 g

, TT-Printed by the Consumer Cooperatives of the Central Bureau of Standards of the Ministry of Economic Affairs 18- This paper size applies to Chinese National Standard (CNS) A4 specifications (210X297 mm) V. Description of the invention (16) A7 B7 Ingredients (mg / 5 ml) Isopropanol 47.0 g propylene_ 10.0 g ethyl acetate 10.0 g active ingredient 1-15 g -C 1 2 fatty acid triglyceride 30 .0 g group. Compounds ... 丄 〆 ingredients (mg / 5 ml) 95.08 g of ethanol butylated hydroxytoluene 0.02 g of active ingredient 1.5-25 g of sister compound 1 3, 1 4, 15 and 16 are in the form of lotion.! Thread (please read the note on the back first) Please fill in this page for further information) Printed by the Central Consumers Bureau of the Ministry of Economic Affairs of the Consumer Cooperatives The paper size is applicable to Chinese National Standard (CNS) A4 (210X297 mm) 389692 V. Description of the invention (17) Group ... (Mg / 5ml) White a Shihlin 50.0 g liquid paraffin 15.0 g refined paraffin 32.0 g active ingredient 1-20 g compound I 1 "amount (mg / 5 ml) white petrolatum 50.0 g liquid parrot 13.0 g refined Of Stone Sloth 32.0 g Active Ingredients 1-20 g-Θ. (Please read the notes on the back before filling this page) Order. Printed by the Central Standards Bureau of the Ministry of Economic Affairs, Machining Consumer Cooperatives, and printing the compound 1 7 and 1 8 Agent form. Give it a try — skin U., shrink ... Write 3 to 20 healthy and postmenopausal women. In addition, choose this song (women's benchmark is that they show several signs of rapid skin atrophy, such as the rapid increase of facial wrinkles or crow's feet, and the rapid change of skin's pigmentation effect. " CNS) 8 4 green (210x297 mm)

Bit: '389693 at ____ B7 V. Explanation of the invention (18) The assessment of this situation is based on the fact that the environmental impact assessment criteria are not worthy of the skin's outliers, and some of them must be treated for their good quality. Or change to the first kind of fixed teeth examination, some self-defense must be injured. Someone outside looks wet. The UV must be eliminated. what. Moisturizing. The amount of disease elimination is like Cheng Cheng's soft complaint and examination of the light, which means that he should hold some positive items more than the pathological skin, compared with the pathological nature of the disease. Because of the transformation of the image of use and confession, it is considered as a shadow of quality. The examiner has some points on the body, and the degree of skin peeling is based on this standard. The speed of sugar from urine and skin high energy can be standardized. "Initial quasi-acidic acid combination is fast" and human is also a free-label or amine polymer or disease contraction fruit serotonin. Proamine "evaluation of wilting is based on the consideration of glucosamine spotting. The skin damage can include some damage. Injury. It can be packaged (please read the precautions on the back before filling in this page). The method of loading is found in "The Menopause", Ed, RJ Beard, UniversityPress Chapter 7 (1977) and "Methods in Skin Research", Ed, Skerrow, D. and Skerrow C.J., John Wiley & Sons Ltd. Chapter 22, " Analysis of Sebaceous Lipids "Section 587- 608 pages (1 985)., And other references cited herein are incorporated herein by reference. Once again, the initial standard points for these quantity factors. Therefore, after selection and preliminary evaluation, women in the clinical process take orally at a single or divided dose of 40 to 400 mg of the active compound of the present invention orally every day. In addition, patients are scheduled to be administered locally during the procedure to the areas most likely to suffer from atrophy. This partial procedure involves the application of an active ingredient according to the invention containing 5 to 50% by weight to the affected area once or twice a day. These processes last up to 12 months. Then evaluate quality and quantity at the right time. The positive result is that the overall quantity index of the patient's nephew is improved and / or the quantity parameters (such as the increase in urinary excretion of hydroxyproline, which means the weight of collagen -21-This paper standard applies to Chinese National Standard (CNS) A4 specification (210X297 mm) Order printed by the Consumers' Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs A7 B7 389692 V. Description of the invention (19) Trees and synthesis have increased), wetting amount, glucosamine poly_, softness of dermatology Or bomb, sex has increased. I road hair .. 齓 Select 3 to 20 women who suffer from vaginal atrophy and have menopause. They are ~ healthy. Due to the highly specific and subjective nature of the condition, the assessment of an effective treatment must be subjective in nature. These patients were asked to keep a journal describing how comfortable it was with vaginal itching and dirt and sexual intercourse. These women were placed in clinical processes similar to the epithelial atrophy. Particular emphasis is given to the use of vaginal suppositories containing from 5 to 25% of the active ingredient of the present invention. A positive result is an improvement in the comfort of sexual intercourse and / or a reduction in vaginal itching or scaling. __ In one or two of the above tests, the use of the compounds described herein was shown with a positive result. (Please read the notes on the back before filling this page)

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Claims (1)

Patent application scope 2. A8 B8 C8 D8 389693 A peony composition suitable for inhibiting skin shrinkage, including a compound of the following formula as an active ingredient 0 II where R1 and R3 are hydrogen, -CH3, -C- (Ci-Ce alkyl), or ηII -C-Ar, wherein Ar · is any substituted phenyl group; R2 is selected from N- Pyrrolidinyl and N-hexahydropyridyl; or pharmaceutically acceptable salts and solvates thereof "according to the scope of patent application No. 1 of the peony sister compound, where the compound is (Please read the precautions on the back first (Fill in this page again) -m · HAH flu · — · Printed by the Shellfish Consumer Cooperative of the Central Bureau of Standards of the Ministry of Economic Affairs -23- This paper size is applicable to China National Standard (CNS) A4 specification (210X297 mm) 1 --- ~ Packing ------ Order ----- ', Line --- ^-38 ;: 6ϋ Α8 Β8 C8 D8 389693 4. The scope of patent application or its hydrochloride. 3. A pharmaceutical composition suitable for suppressing vaginal atrophy, comprising a compound of the following formula as an active ingredient 0 I! Wherein R1 and R3 are hydrogen, -CH3, -C-(Ci-Ce Wanyl), or 0 II -C-Ar, wherein Ar is any substituted phenyl group; R2 is selected from N- Pyrrolidinyl and H-hexahydropyridyl; or a pharmaceutically acceptable salt or solvate thereof. According to the peony elder sister compound in item 3 of the scope of patent application, the compound is (please read the precautions on the back before filling this page) — ΘΓ Binding -------- line! Printed by the Central Laboratories of the Ministry of Economic Affairs Or its 鞔 酸 翮 24- This paper size applies to China National Standard (CNS) A4 specification (210X297 mm)