TW434017B - The pharmaceutical composition of pregnane 3,20 diols - Google Patents

Abstract

This invention provides a compound having the formula wherein R and R1 are each, independently, hydrogen or SO3<SP>-</SP>X<SP>+</SP>; X<SP>+</SP> is alkali metal, alkaline earth metal, ammonium, alkylammonium containing 1-6 carbon atoms, or dialkylammonium containing 1-6 carbon atoms in each alkyl group, or trialkylammonium containing 1-6 carbon atoms in each alkyl group; with the proviso that R and R1 are not both hydrogen, which is useful as a progestational agent.

Description

4 3 4CM7 * ^ ______ i. Description of the invention (4 A7 B7 Background of the invention The use of natural cockroach pure and low-toxic estrogen compositions such as pREMARi] i (co-roll equine estradiol) has become an improvement of estrogen deficiency Menopausal syndromes for women and other hormone-related disorders, better treatment of osteoporosis / osteoporosis, β-estrogen composition-estrogen component of general natural estrogen composition-estrogen, maleenone, dehydromamen Estrone, 17_ Ling_estradiol, monohydrodehydroestrone estrone and 17-/?-Dihydrodehydroestrone estrone sulfate (US Patent 2,834,712h estrogen composition is usually organic or inorganic The gold salt of acid test is stable or stabilized at a generally neutral pH ^ 6.5 to 7.5. Urea has also been used as a stabilizer (Us 3,608,077). An anti-gasification agent is mixed to stabilize and synthesize conjugated estrogen and ginseng ( The failure of hydroxymethyl) aminomethane (TRIS) to control pH to prevent hydrolysis is discussed at (js · 4,154 82.) The three compounds described here are 5α-pregnane-3β, 20 /?-Dihydrogenase 3-sodium sulfate Salt, 5α-pregnane-3 therapy, 20 /?-Diol 20-sulfate sodium salt and 5β-pregnane-3, 2M -diol 3,2 (1- (贰) Ester (贰) sodium salt is a small amount of PREMARIN (conjugated equine estrogen). Preparation of 3_Hydroxy_5,7,9-Estradiol-17-Copper is shown by β · Banajeje 掲 in Ind .Chi ·. Beige · Suppl · 2: 4 3 5 (1 9 5 9); but the use of this compound is not provided. DESCRIPTION OF THE INVENTION According to the present invention, a compound of the formula {谙 read the precautions on the back before filling in this page)

-m I I I 4iJ · ir This paper size is applicable to Chinese storehouse standard (CNS) A4 specification (210X 297 mm) 4 3 40 1 la A7 B7 V. Description of the invention (&gt;)

• ml ------- · The jealousy ministry has a low standard and the labor and consumption are combined. The printing of the company I is where R and R 1 are hydrogen or S 0 3 ~ X + respectively; X + is an alkali metal, Alkaline earth metals, ammonium, alkylammonium containing 1-6 large atoms, or dialkylammonium containing 1-δM large atoms in each alkyl group, or trialkylammonium containing 1-6 sulfonium atoms in each alkyl group; However, R and R 1 are not both hydrogen. Because 5 α-pregnane-3 / ?, 20-diol 3-sulfate sodium salt, 5 α-pregnane-3, 20-diol 20-sulfate sodium salt and 5α-pregnane-3 / S, 20々-diol 3,20- (贰) sulfate (贰) sodium salt is a small amount of PREMARIH (conjugated horse estrogen), so the present invention also provides 5 «-pregnancy greater than U purity Alkane-3 Office, 20y8-di_3-sulfate sodium salt, 5α-pregnane-3 / ?, 2 G /?-Diase 20-0-sulfate sodium salt and purity greater than 1% 5 «-Pregnane-3β, 21) / 5-Diferment 3,20- (贰) sulfate (酯) sodium salt. The present invention also provides a compound mainly containing 5 α-pregnane-3 ^, 20-diol-diol 3-sulfate SS sodium salt, and a compound containing 5α-pregnane-3, 20 α-diol 20- 碕Compound of sodium salt of sodium ester and a compound mainly containing 5 α-pregnane-3 /-, 2 (1β-diol 3,20- (贰) sulfate (贰) sodium salt β (Please read the note on the back first Please fill in the items again to buy) This paper size is applicable to Chinese National Standard (CNS) A4 specification (210 × 297 mm) 4340 17 ^ a7 _B7__ V. Description of the invention (4) The present invention also provides a substance composition mainly comprising a compound of the following formula

This paper size applies to the Chinese National Standards (CNS) A4 specification (21 ×: 297 male acid) 4340 17 'Α7 Β7 Printed by the Ministry of Standards and Standards Bureau of the People ’s Republic of China ^ V. Description of the invention (4) Ammonium, Or a dialkylammonium salt having 1-6 sulfonium atoms in each alkyl group, or a trialkylammonium salt having 1-6 sulfonic atoms in each alkyl group; as a progestational agent. The compounds of the present invention can be prepared from readily available starting materials according to the methods of Reaction Schemes I-III. For example, according to Reaction Scheme I, 5cr-pregnane-3 &quot;, 20-N-diol (I) [DMGlick and H. Hirschmann, J. Org. C he M. 2 7, 3 2 1 2 (1 9 6 2)] Triethylamine with two or more equivalents: sulfur trioxide reactant in a suitable solvent such as tetrahydrofuran at room temperature 5α; -pregnane-3 &quot;, 20 / 3-diol (贰) sulfate, (贰) triethylammonium salt (2a) e triethylammonium salt (2a) were obtained by ion exchange chromatography (Dewey ( Dowex) 50X8, Na +) into sodium salt (2b). According to Reaction Diagram II, 5 cr-pregnane-3 is commercially available, and 20-diol-diol-3 -acetic acid vinegar (3) [K. Klyne and DHR Barton, J. Am. Chem Soc. 7i, 1500 (1949 )] Treated with one or more equivalents of triethylamine; three gasification sulfur reactants to obtain 5α-pregnane-3β, 20diol-3-acetate-20-sulfate, triethylammonium salt (4 ). Triethylammonium salt (4) is treated with a methanol / sodium hydroxide aqueous solution to obtain 5α-pregnane-3yS, 20 / fluorene-diol-20-sulfate sodium salt (5). According to the reaction diagram III, 5α-pregnane-3 / S, 20-diol-20-acetic acid fi purpose (β) [according to S. Butenandt, and J. Schmidt, Chetn. Ber. Fi 7, 1 8 9 3 The procedure of (1 9 3 4) was prepared from 5 a -pregnane-3, 20 / fluorene -diol-diacetate]. It was obtained by treating with one or more equivalents of triethylamine: sulfur trioxide reagent. 5α-pregnane Θ, 20-diol-20-acetate-3-sulfate, triethylammonium salt (7). The triethylammonium salt (7) was treated with an aqueous solution of methanol / hydrogenated sodium hydroxide to obtain 5α-pregnane-3, 20-glycol-3-sulfate sodium salt (8). (Please read the precautions on the back first / 34-watt-pack, ιτ The paper size is applicable to the Chinese National Standard {CNS) A4 specification (, also 2 to 7 mm) 434017 ^ A7 B7 Central Standard趵 Only Η eliminate the print of cooperatives

Xiang Zai L · This page KK Please read the back of the first book of the bookbinding booklet 中 中 中-h 0- / 0h.T. Consumer Cooperative Press 4 3 40 1 at B7 ________________- ~ ------------ --- Five 'invention description U) The progesterone activity of a representative compound of the present invention (5α-pregnane_3jS, 20; β-diol) is evaluated in a test tube in a quasi-pharmacological test procedure. The results obtained are briefly as follows.结果 The results of the quasi-pharmacological test procedure verify that the compounds of the present invention are -progestinic. This test is based on Cheng Sunning, and Heheji 1 is quantified based on its use in stimulating test phosphatase activity in T41PJ8 cells (a type of high-capacity human-1 milk). This is a well-established test course m ~, the response of the body ketone to the hip stimulation by live ΊΓϊϊ_1 &quot; ϊϊ is fine, one ..... one -_ **--«»-. &Gt; _, one _ |-I -----, Endogenous. Cells were preconditioned in low serum medium for one day, and then treated with _ · _, Μ ^ ιιΤΤιΙ —1-ΤΊ r it I m '*' _ I ·· 11 &quot; '· — &quot; Jl' '—-II _ 1 ^^ · Test compound treatment. 24 hours after treatment, the alkaline phosphatase activity was measured. Ketones such as progesterone and Metso pregnant noodles! Acetate (medroxyprogesterone, ~ ______ W- '·-* · * 1 &quot; _llSW ...... H _ acetate) induces 30-60 times salty phosphatase and only needs to be low ~~ _ll.- · _ II I Ml · · ** · .. · '.,! Μι · * ιι · ι lull · ιι,. ^ Ι ^ Γ ... „ΜΜ — the most important action. The test induced by progesterone jut-m-is -Live ^ Hu J_X &gt; U »Π» »« * · &quot;, · &quot; ,, ^ ,, &quot; * Ι &gt;, · *** · &quot; &quot; ― &quot; '* Antagonist If RU486 is blocked or inhibited, it indicates the specificity of the response. When evaluated in &amp; sequence, 5α-pregnane-3 / ?, 20 /?-Diol has A50)

Progesterone activity. ~ _ ------- &quot;:, ~ The neuroprotective and cognitive enhancement effects of the It composition of the present invention are pseudo-evaluated in a test tube in a quasi-pharmacological test procedure, which measures 5 α-pregnanol (as this The representative compound of the invention) the effect on the current of calcium and potassium pathway \ 一 __ ^ -------------------------------- -Toward. In short, β recording technology records calcium and potassium currents from cultured hippocampal neurons. Compounds to be evaluated were freshly prepared daily with 4 Q 0 # Μ ethanol sample preparation solutions. The test compound is diluted in saline to obtain a final concentration of 2 # Μβ. At least 10 current tracer controls, test compounds, and -8 in various conditions.-This paper is suitable for China National Standards {CNS) A4 size (210 乂 297). Li> Please read the back first

Page I Order Printed by the Standard Department of the Ministry of Economics and Industry, printed by the standard D laboratories and warehouses ^ 4 3 4 0 17 ^ A7 _B7__ 5. Description of the invention (7) Calcium or potassium current amplitude of the eluted solution. To compensate for the decrease in calcium current over time, find the control and washout current averages. Divide the current amplitude of the drug by the average of the control and washout currents to determine the percentage change. The mean, standard deviation, and error of each test compound were calculated and the significant difference between the test group and the control group was determined using the paired T test. 5 «-pregnane-3, 20 / 3-diol compared to the control group can increase potassium pathway current by 19.95 ± 3.46% (p = 0.0005), indicating 5« -pregnane-3y8,20 彡 -diol height 搔Neurons, so it is easier to respond to other stimuli. Compared with the control group, the calcium pathway current did not change significantly (increased by 2.2 (^ 0.97 90). These results show that the compound can be used to protect against seizures and to improve cognition. The compound of the present invention is a progestin agent. It is based on quasi-pharmacology As a result of the test procedure, the compound of the present invention can be used as an oral contraceptive (men and women), hormone replacement therapy (especially in combination with estrogen), for treating endometriotic luteum defects, benign breast and prostate diseases, and Prostate cancer and endometrial cancer. The compounds of the present invention can also be used to protect against seizures, increase cognition, treat Alzheimer's disease, dementia, vasomotor symptoms associated with menopause, and other central nervous system disorders. The compound of the invention can be used to stimulate the production of red blood cells. The compound of the invention can be used alone as the sole therapeutic agent, or can be used in combination with other agents such as other estrogen, progesterone or / androgen. The carrier formula is for administration. The formula ratio is based on the solubility and chemical properties of the compound, the selected route of administration and standard pharmacology. Practical decision. The peony drug carrier can be solid or liquid. The solid carrier includes one or more substances, and it can also be used as a flavoring agent. The size of this paper applies the Chinese National Standard (CNS) A4 specification (210X297). (Read the notes on the back and fill out this page)

Printed by the central government if '^ Ju Workers ’Cooperatives Cooperative Society !! 434017, A7 __ £ 7 ___ 5. Description of the Invention (ί) Lubricants, solubilizers, suspending agents, fillers, sliding agents, tabletting ribs, sticking Or tablet disintegrating agent; it may also be an encapsulated substance. In powders, the carrier is a finely divided solid and its mixed and finely divided active ingredients. In the lozenge, the active ingredient is mixed with an appropriate proportion of a carrier having the required tableting properties and is compacted into the desired shape and size. Powders and lozenges preferably contain 99% high active ingredient. Suitable solid carriers include, for example, calcium phosphate, magnesium stearate, talc, sugars, lactose, dextrin, starch, gelatin, cellulose, methyl cellulose, sodium carboxymethyl cellulose, polyvinylpyridine, low Melting point wax and ion exchange resin. Liquid carriers can be used in the preparation of solutions, suspensions, emulsions, syrups, elixirs and pressurized compositions. The active ingredient may be dissolved or suspended in a pharmaceutically acceptable liquid carrier such as water, an organic solvent, a mixture of the two, or stork-acceptable oils or fats. Liquid carriers contain other suitable pharmaceutical additives such as solubilizers, emulsifiers, buffers, preservatives, sweeteners, flavoring agents, suspending agents, thickeners, colorants, viscosity modifiers, stabilizers, or osmotic pressure regulators. . Examples of liquid carriers for oral and parenteral administration include water (partially containing procyanidin additives such as cellulose derivatives, preferably sodium carboxymethyl cellulose solution), alcohols (including monohydric alcohols and polyhydric alcohols such as dienzymes), and Its derivatives, lecithins and oils (such as fractionated coconut oil and peanut oil). For parenteral administration, the carrier can also be oily, such as ethyl oleate and isopropyl myristate. Liquid carriers can be used as sterile liquid dosage compositions for external administration. The liquid carrier of the pressurized composition may be a halogenated hydrocarbon or other peony acceptable propellant. Liquid pharmaceutical composition without ® solution or suspension can also be borrowed, for example, -1 0-(Please read the notes on the back before filling in this treasure) The paper size of the book is applicable to China National Standards (CNS) A4 specification (210 × 297 (Mm) The central standard of the Ministry of Economics ^ 杓 ^ 工 消 贽 合 竹 社 印 &quot; 4340 17, at _B7____ V. Description of the invention (?) Intramuscular, intraperitoneal or subcutaneous injection. Blueless solutions can also be administered intravenously. The compounds of the invention may also be administered orally in the form of a liquid or solid composition. The compounds of this invention can be administered transrectally or vaginally in a conventional suppository form. For administration by inhalation or insufflation in the thorium or bronchus, the compound of the present invention can be formulated as an aqueous solution or a part of the hydration solution, and then can be used in the form of an aerosol. The compound of the present invention can also be administered transdermally. By using a transdermal patch, it contains the active compound and a carrier. The carrier is inert to the active compound and non-toxic to the skin. The drug can be transported through the skin to the blood system. Carriers can be in a variety of dosage forms such as emulsifiers and emollients, pastes, gels, and barrier devices. Emulsifiers and softeners can be water-in-oil or oil-in-water viscous liquid or semi-solid emulsions. Also suitable for pastes include grazing powders dispersed in paraffin wax or hydrophilic stone moth containing active ingredients. A variety of barrier devices can be used to release active ingredients into the bloodstream. For example, semi-permeable membranes cover active ingredient reservoirs (with or without a carrier) or active ingredient-containing matrix β. Other barrier devices are known in the reference literature. Dosage requirements will vary depending on the particular composition used, the route of administration, the severity of symptoms, and the individual to be treated. Based on the results of the quasi-pharmacological test procedure, the daily dose of the active compound is expected to be 0.02 g / kg-7 5 (1 μg / kg. Treatment usually begins with a small dose of the optimal dose of the compound and subsequently increases the dose to reach The best results under the circumstances; the correct dosage for oral, external, oral, or bronchial administration will be determined by the prescribing physician based on the experience of treating a wide range of patients. The preferred peony compositions are in unit dosage forms such as lozenges or Capsules β in these dosage groups-11- (Please read the precautions on the back before filling this page)

、 1T _ This paper size applies to Chinese National Standard (CNS) Λ4 specification (210X 297 mm) 43 pieces printed by the central standard of the Ministry of Consumer Affairs and Consumers Cooperatives 丨 7 ~ A7 ------ B7_ V. Description of the invention (, ") The composition can be subdivided into individual preparations containing an appropriate amount of active ingredients; unit doses can be packaging compositions such as packaged powders, vials, ampoules, pre-filled syringes or carcass-containing medicine bags. Unit doses M can be, for example, a capsule or lozenge itself, or it can be a suitable amount of the composition in a packaged form. The preparation of a representative compound of the present invention is provided below. Example t-Pregnane-3 / 3.20 / 3-Seijin-3.20- (glycoside ) Sulfur _, Anti-S_iL®L (2a) 5 «-Pregnane-3 in, 20 Office-diol {1) (3.0 g, 9.375 mmol) dissolved in 3 60 ml of tetrahydrofuran and 100 ml of digas Methane. Add a solution containing 0.8 g of oxidized ethylamine sulfate complex (39.6 mmol), and stir at room temperature for 21 hours. Bingo removes methane. The residue is filtered in a Buckner funnel. The title compound was obtained as a white solid (4.98 g, 78%) by washing with tetrahydrofuran and dehydration for 20 hours. 1 H NHR (300 ΜΗ, D Μ S 0-fl e) δ 0.70 (s, 3H), 0.75 (s, 3H), 1.18 (t, 18H), 1.55 (m, 4H), 1.79 (m, lH), 2.15 (d, J = I2 .3Hz, 1H), 3.09 (m, 12H), 3.93 (m, lH), 4.06 (m, lH); m /;? (ES negative) 479 (MH) 5_a .-- mu〇 立 二 ( 2h) Crude triethyl ammonium salt (2 a) was dissolved in 250 ml of distilled water and the solution was passed through an ion exchange column (Dewey 5 X 8 N a + -type U column, washed with 10 B ml of distilled water, And eluent were lyophilized; δ _ 8 g (8 2. 9%) β product at 1 A 〇〇1-2-1 This paper size applies the Chinese National Standard (CNS) Λ4 specification (210X297 mm) ---- ^ ------- Dare-(please read the precautions on the reverse side and fill in the reverse page). Ding &quot; ff ^ f I am surprised by the central part of the dripping section ', Μ 工 消 贽 合 竹 衣 印来 4 3 4 0 1 7 at __B7__ V. Description of the invention (,) liters of methanol search and dripping. The filtrate was concentrated by vacuum and the solid product was collected with ether, filtered and dehydrated in a Buckner funnel to obtain the title compound. White solid (6.1 g, 74%). 0 0.69 (s, 3 Η), 0.7 4 (s, 3 Η), 1.5 4 (m, 5Η), 1.8 0 (d, J = 9.7Hz , lH), 2.17 (d, J = 12.6 «z, 1Η), 3.08 (m, lH), 3 _ 9 (m, 1 Η), 4 0 5 (m, 1 Η) m / z (ES negative) 4 7 9 (Μ-Η) 〇S_ @ L2_ -β -7, m Μ. -20 β,-. 7, mm K4) 5〇:- Pregnane-3 &gt; 3-acetamidine-2 (3 /?-Alcohol (3) (7.5 g, 20,63 mmol) was dissolved in 700 ml of tetrahydrofuran and sulfur trioxide-triethylamine complex was added (13 grams, 47.7 millimoles). The mixture was stirred at room temperature for 20 hours and filtered. The filtrate was concentrated in vacuo and the residue was triturated with ether. The precipitate was collected in a Buckner funnel and washed with ether and dehydrated to give the title compound as a white solid (9.6 g, 86%). 1 H NMR (300 MHZ, DHS〇-de) &lt; y 0.70 (s, 3H), 0.78 (β, 3Η), 1.18 (ΐ, 9Η), 1.96 (3, 3Η), 2. 1 6 ( d = 1 2. 7 Η z, 1 Η), 3. 1. 0 (¢), 6 Η), 4 〇6 {ra, 1 Η), 4.5 6 (in, 1 Η); ϋΐ / ζ (Ε S ft) 4 4 1 (Μ-Η) 2 m Yi Yi 5) crude triethylammonium salt (0 dissolved in 30 G ml of methanol and 100 ml of IN sodium hydride β mixture jt mixed for 72 hours and crude Produced in Buckner Funnel-1 3- (Please read the notes on the back before filling this page) ^ The size of the paper is applicable to China National Cotton Standard (CNS) A4 (210X297 mm) 434017 t A7 B7____ printed by the quasi-government consumer goods cooperative. V. Description of the invention (Θ) Filtration and vacuum dehydration for 20 hours. The material was stirred and filtered in i 0 β ml of methanol. The filtrate was diluted with 40 D ml of ether and stirred 1 After 8 hours and filtration on a Buckner funnel, the title compound was obtained as a white solid (3.6 g, 48%). 1 H NMR (3Q0 MHz, fiMS0-de) 0 6 9 (s, 3 Η), 0, 7 4 (s, 3 Η), 2. 1 7 (d, J = 1 2 · 7 Η z, 1 Η), 4.08 4. 4 1 (d, J = 4.6Hz, 1H); m / z (ES negative) 3 9 9 (MH); Analysis (C2; LH35〇s SNa): Calculated value C 59.69; B 8.35; Real tide value C 5 9. 2 8; H 8 · 0 7. Ning Li: i- Pregnane-.?.0θ-Diacid Squalol-3-Sulfuric Acid Brewery, bis.Z (7) 5 «-Pregnane-3 o'clock, 20-diol-20-acetate (6) [According to A. Butenandt, J. Schmidt, C hem. Be r. 67, 1893 (1934) was prepared from a commercially available 5α-pregnane-3 / 3, 2 >> 0-diol diacetate] ( 0.75 g, 2 mmol) was dissolved in 1 fl ml of tetrahydrofuran and triethylamine-sulfur trioxide complex (G. 45 g, 25 mmol) was added. The mixture was stirred at room temperature for 20 hours. Added After 30 ml of ether, the formed precipitate was collected on a Buckner funnel, washed with a shaft and dehydrated to obtain the title compound as a white solid (0.8 g, 10%). 1 H NMR (30fl MHz, DMS0-d6) δ 0.5 4 (s, 3 Η), Q. 7 6 (s, 3 Η), 1-〇8 (d, 3 Η), 1. 2 0 ( t, 9 Η), 1. 9 fi {s, 3 Η), 3. 10 (r3, 6 Η), 3. 9 0 (m, 1 Η), 4. 7 1 (m, 1 Η), 8 . 9 0 (s, 1 Η); -1 4-(Please read the notes on the back before filling this page)

This paper size applies the Chinese National Standard (CNS) A4 specification (210X297 mm) Λ340 1 A7 B7 V. Description of the invention (3) m / z (ES negative) 4 4 1 (Μ-Η) 5 α -Pregnancy 镋 -3 θ .2 0/9-Disulfanilate, Napu (8) 50: -pregnane-3, 200,000-diol-20-acetate-3-sulfate, triethylammonium salt (7) (1.3 g, 24 milliliters) dissolved in a mixture of 50 ml of a 2D% aqueous sodium hydroxide solution and 50 ml of methanol. The mixture was stirred at room temperature for 30 hours. The methanol and aqueous solution were removed in vacuo and extracted with 30D ml of n-butanol. The butanol solution was filtered through Celite (C e 1 ite) and concentrated in vacuo to obtain a glassy residue. The residue was dissolved in ethanol and charcoal was added. The mixture was filtered through Celite and concentrated in vacuo to obtain a solid residue. The residue was triturated with 500 ml of ether, collected in a Buckner funnel and dehydrated to obtain the title compound as a white solid {(K3 g, 79%). 1 H NMR (30 D MHZ, DHSO-de) &lt; 50.68 (s, 3H), 0.78 (s, 3H), 1. 10 ({d, 3 H), 1.8 3 (d, 1 H), 2.11 (d, lH) 3.48z (q, lH), 3.93 (βι (1Η), 4.06 (ιβ, 1Η) 4.34 ¢ 1,1H) is / z (ES negative) 3 9 9 (M-H ) nk, read the notes on the back of the book, then fill in the page I. Scripture ^-Ministry of Standards and Standards *.

This paper size applies to China National Standard (CNS) A4 (2IOX297 male f)

Claims (1)

Yunwei 434017 No. 87 1 065 14 "Patent for the pharmaceutical composition of pregnane 3,2diols (Amended in March 89) A. Application scope of patent: 1. A pharmaceutical composition with progestin activity ' Which contains a compound of the formula Where R and R1 are each hydrogen or SoX +; X is sodium, or trialkylammonium with 1-6 carbon atoms in each alkyl group: but R and R1 are not both hydrogen, and the sauce carrier is 2 The pharmaceutical composition in the scope of patent application No. 1 can be used for progestin therapy. 3. The pharmaceutical composition in the scope of patent application No. 1 can be used in mammals in need to treat or inhibit cancer, central nervous system disorders, dementia. Or Alzheimer's disease. This paper scale is applicable to the National Standard (CNS) A4 specification (210 X 297g) 89. Η. 23 ft :; year / 1 2 乂. 2 1 4¾ / i V Λ Application for the “Phase Π, Heart β Case No. 87106514. Categories (the above are test notes from the Bureau) A4 C4 43401 'If 鎏 Patent Specification Central Government Bureau of the Ministry of Economic Affairs of the Consumers Cooperatives Co., Ltd. First, the invention is mainly composed of Chinese pregnane 3,20 diol medicines ^ Β, the new English of PHARMACEUTICAL COMPOSITION OF PREGNANE 3,20 DIOLS name 1. ReUhold HW Bende ("ReUhold HW Bende") 2. Ho "ace Fletcher Iil" 3. Wenzhong J. Huang 4. Michael Z. Kagan 5. Syed M. Shah Nationality 1.-5. All screens US-Invention Α- 、 Creation Α Living and Residence 1. 101 Liverpool Grove Road, Pennsylvania 19481, United States 2. 2382 Kingsfield Road, Houston 19464, Pennsylvania 3. United States, New Jersey 08876 Samoville No. 8 Weir Lane 4. No. 4 Roman Kensie Lane, Plainsboro, New Jersey 08536, United States 5. East Hanford, New Jersey 07936, United States No. 13 Waiting Road Name (Name) American Home Products Co., Ltd. Aner i can Hone Products Corporat i on National borrowing United States III. Applicant's residence and residence United States New Jersey 07940-0874 Mandison 5 Gillard Farm (Business The name of the representative is Egon E. Berg (Egon E. Berg) This paper size is applicable to China National Standards (CNS) 8 4 specifications (210X297 mm) ^^^ 1 tn n ID ^ fJu mi-1 _ 1 -I nbM-IJ—-i- ffl In — ^ ϋ I --1-. I Yunwei 434017 No. 87 1 065 14 "Patent for Pregnane 3,2diols Pharmaceutical Composition j Patent (89 Amendment in March) A. Patent application scope: 1. A progestin-active pharmaceutical composition 'comprising a compound of the formula Where R and R1 are each hydrogen or SoX +; X is sodium, or trialkylammonium with 1-6 carbon atoms in each alkyl group: but R and R1 are not both hydrogen, and the sauce carrier is 2 The pharmaceutical composition in the scope of patent application No. 1 can be used for progestin therapy. 3. The pharmaceutical composition in the scope of patent application No. 1 can be used in mammals in need to treat or inhibit cancer, central nervous system disorders, dementia. Or Alzheimer's disease. This paper size is applicable to the National Standard (CNS) A4 specification (210 X 297 g)