CN104013611A - Application of mango aglycone and derivative thereof in preparation of anti-prostate hyperplasia drug - Google Patents

Application of mango aglycone and derivative thereof in preparation of anti-prostate hyperplasia drug Download PDF

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CN104013611A
CN104013611A CN201410269681.1A CN201410269681A CN104013611A CN 104013611 A CN104013611 A CN 104013611A CN 201410269681 A CN201410269681 A CN 201410269681A CN 104013611 A CN104013611 A CN 104013611A
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reductase
mango aglycone
activity
prostate
alpha
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CN104013611B (en
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刘一丹
齐美凤
王萍
宋立明
李小英
张建文
张伟
尚建华
其他发明人请求不公开姓名
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Safe Metabolic Arthritis Gout Of Yunnan Awns Research Center
Kunming Pharmaceutical Corp
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Safe Metabolic Arthritis Gout Of Yunnan Awns Research Center
Kunming Pharmaceutical Corp
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Abstract

The invention belongs to the field of medicines, and discloses novel application of a mango aglycone derivative. An in-vitro test shows that the mango aglycone derivative can obviously inhibit activity of 5 alpha-reductase, can remarkably lower prostate wet weight index of a testosterone propionate replication prostate hyperplasia model mouse, can lower a ratio of E2/T in blood serum, and can lower activity of the 5 alpha-reductase in a liver tissue, so that the mango aglycone derivative is indicated to have effect in inhibiting activity of 5 alpha-reductase, can be used for treating 5 alpha-reductase expression or superhigh-activity-associated diseases, for example testosterone propionate; moreover, the mouse stomach is filled with the drug in maximum administration dosage of 21.6g/kg, and therefore, the drug has very good clinical application prospect.

Description

Mango aglycone and derivant are in the application of preparing in Drugs against benign prostate hyperplasia thing
Technical field
The present invention relates to medical technical field, be specifically related to mango aglycone and derivant thereof in the application of preparing in Drugs against benign prostate hyperplasia thing.
Background technology
Benign prostatic hyperplasia (BPH) is a kind ofly obviously to increase and occur the middle-aging male commonly encountered diseases that carrying out property frequent micturition, dysuria are feature because of prostate.Epidemiological study demonstration, sickness rate was very low in the past in 40 years old for hyperplasia of prostate, within 50 years old, accounted for sickness rate after 40%, 80 years old and approached 90%, during by 90 years old, learned almost 100% discovery prostatic hyperplasia of inspection if carry out prostata tissue.Along with the aging of China's population, its sickness rate is in rising trend in recent years.
The therapeutic modality of prostatic hyperplasia is mainly divided into operative treatment and Drug therapy.Excision once had once been considered to effect a radical cure the prefered method of BPH, but patient's problem at advanced age often makes again operative treatment have certain limitation, easily causes multiple complications, postoperative complication approximately 15% according to statistics, case fatality rate approximately 1%.Have research to point out, prostate can produce panimmunity globulin, can synthesize have multiple antibacterial action containing zinc polypeptide, there is protection reproductive system and exempt from the Effects on local immunological functions of antibacterial and the invasion and attack of other pathogenic microorganisms, should retain as far as possible.
Cause that the Etiological of BPH is relevant with the rising of dihydrotestosterone content in prostata tissue.5α-reductase energy catalysis testosterone (T) is reduced to the reaction of dihydrotestosterone (DHT) in vivo, and the activity that suppresses 5α-reductase can reduce the content of dihydrotestosterone in prostata tissue.Research shows to express to 5α-reductase or the relevant disease of hyperactivity have prostatic hyperplasia, carcinoma of prostate, androgenetic alopecia, female hirsutism, acne (Wu Xueyan etc. steroid 5α-reductase and 5α-reductase 2 type Defect progress, preclinical medicine and clinical, 2006,3:225.Li Yongfang etc. in plant, suppress the study of active components progress of 5A-reductase, Chinese herbal medicine, 2006,11:1740).
In recent years, Drug therapy BPH becomes main treatment means gradually, mainly contains 5α-reductase inhibitor, alpha-2-adrenoceptor antagonists, plant amedica and Chinese patent medicine.The contraction state of alpha-blocking agent prostate smooth musculature cells capable of blocking, the urethral stricture that alleviates Patients with Prostatic Hyperplasia is blocked; 5 alpha reductase inhibitors, can suppress in prostate testosterone to the conversion of dihydrotestosterone, thereby dwindle the prostate volume of hypertrophy.Be no matter suit the medicine to the illness, to because of or therapeutic alliance, all can recover in various degree the urinary function of Patients with Prostatic Hyperplasia, improve its quality of life, but chemicals life-time service all has obvious adverse reaction, and Chinese patent medicine preparation has material base and effective ingredient is not clear, action target spot is unclear, quality control is difficult, curative effect is difficult to the present situation ensureing.
Have the antibacterials of data sheet express contract 80% and 60% anticarcinogen directly or indirectly to come from natural product, natural drug is just becoming the important source of human treatment's drug development.Have not yet to see natural drug 5α-reductase is had to obvious inhibitory action and the report in anti-prostatic hyperplasia application aspect.
Summary of the invention
The object of the present invention is to provide the new purposes of natural drug mango aglycone and derivant thereof.
Research in recent years is found, mango aglycone is the active metabolite of chimonin, there is antioxidation, suppress the multiple pharmacological effect such as PTP1B activity, blood sugar lowering, antitumor, uric acid resisting and gout, but mango aglycone content in plant is extremely low, the simple plant extraction process that relies on is difficult to satisfy the demand, inventor makes the mango aglycone derivant of a series of purity >98% early stage by synthetic, be buff powder, and structural formula is:
Wherein, R 1, R 2, R 3, R 4for H or acetyl group.
The invention provides the compound with following structural formula in the application of the medicine of the preparation treatment disease relevant to 5α-reductase expression or hyperactivity,
Wherein, R 1, R 2, R 3, R 4for H or acetyl group.
The present invention has carried out inside and outside pharmacodynamic study to mango aglycone and derivant thereof.Result shows: mango aglycone and derivatives thereof have inhibition activity in various degree to 5α-reductase, and its inhibition activity to 5α-reductase is linear dependence; Gastric infusion 21 days continuously, mango aglycone can obviously alleviate ratio that Testosterone Propionate copies E2 and E/T in the prostate weight in wet base of prostatic hyperplasia model mice and index, reduction serum, reduce 5α-reductase activity in liver organization, show that it can effectively suppress 5α-reductase activity, have and treat to the disease that 5α-reductase is expressed or hyperactivity is relevant as the effect of prostatic hyperplasia.
As preferably, described and 5α-reductase are expressed and are increased or disease that hyperactivity is relevant is prostatic hyperplasia, carcinoma of prostate, androgenetic alopecia, female hirsutism or acne.
More preferably, the effective dose of described compound is 10-1000mg/kg/d.
Of the present inventionly experimental results show that mango aglycone does not show lethal toxicity in chmice acute toxicity test, the one in a few days maximum tolerated dose of gastric infusion exceedes 21.6g/kg, is equivalent to 1440 times of allogenic animal pharmacodynamics effective dose 15mg/kg.
Mango aglycone of the present invention and derivant thereof can directly be applied separately, also applied in any combination mutually; Can comprise that plant extract composition compound recipe form is used, and also can make in a usual manner health product and food form and use with other drug; Mango aglycone derivant of the present invention adds tablet, granule, capsule, pill, suspensoid or the injection that pharmaceutically acceptable adjuvant is made to use.Mango aglycone and derivant structure thereof are simple, and easily chemosynthesis, has higher potential applicability in clinical practice.
Brief description of the drawings
Fig. 1 is the relation of albumen and the absorbance of variable concentrations;
The linear relationship of the different testosterone amounts of Fig. 2 and peak area;
The impact of the different enzyme concentrations of Fig. 3 on enzyme activity;
The impact of the different testosterone concentrations of Fig. 4 and enzyme activity;
The impact of the NADPH of Fig. 5 variable concentrations on enzyme activity;
The inhibitory action of Fig. 6 finasteride to 5α-reductase;
The inhibitory action of Fig. 7 mango aglycone to 5α-reductase;
Figure 81-hydroxyl-3, the inhibitory action of 6,7-triacetoxyl group mango aglycone to 5a-reductase;
Figure 93-hydroxyl-1, the inhibitory action of 6,7-triacetoxyl group mango aglycone to 5a-reductase;
Figure 101,3-dihydroxy-6, the inhibitory action of 7-diacetoxy mango aglycone to 5a-reductase;
Figure 116,7-dihydroxy-1, the inhibitory action of 3-diacetoxy mango aglycone to 5a-reductase.
Detailed description of the invention
The invention discloses mango aglycone and derivant in the application of preparing in Drugs against benign prostate hyperplasia thing, those skilled in the art can use for reference content herein, suitably improve technological parameter and realize.Special needs to be pointed out is, all similar replacements and change apparent to those skilled in the artly, they are all deemed to be included in the present invention.Application of the present invention is described by preferred embodiment, and related personnel obviously can change methods and applications as herein described in content of the present invention, spirit and scope or suitably change and combination not departing from, and realizes and apply the technology of the present invention.
In order to make those skilled in the art understand better technical scheme of the present invention, below in conjunction with specific embodiment, the present invention is described in further detail.
Embodiment 1: the external inhibitory action to 5α-reductase
1, experiment material
The female Mus of SD, Kunming medical university; Testosterone, Yuan Ye bio tech ltd, Shanghai (20130409); NADPH, sigma company (Lot SLBC6718V); Finasteride, Hubei Shubang Pharmaceutical Co., Ltd. (20121001); Tris-base, BIOSHARP company (Amresco0497); Sodium chloride, Sheng Gong biotech firm (Lot3004B220); DTT, sigma company (Lot BCBK8875V); Dehydrated alcohol, Yunnan Shan Dian pharmaceutcal corporation, Ltd (Lot LN70N21); Dichloromethane, Tianjin Fengchuan Chemical Reagent Science & Technology Co., Ltd. (20100926); Chromatograph methanol, Beijing lark prestige Science and Technology Ltd. (116481); Mango aglycone; 1-hydroxyl-3,6,7-triacetoxyl group mango aglycone; 3-hydroxyl-1,6,7-triacetoxyl group mango aglycone; 1,3-dihydroxy-6,7-diacetoxy mango aglycone; 6,7-dihydroxy-1,3-diacetoxy mango aglycone, purity is all greater than 98%, and Kunming drug research institute of pharmacy group provides.
2. experimental apparatus
DHG-9245A electric drying oven with forced convection, Shanghai Yiheng Scientific Instruments Co., Ltd; Biofuge high-speed refrigerated centrifuge, Thermo company; E2695 high performance liquid chromatograph, Waters company.
3. experiment content
3.1 protein quantification
Female sd inbred rats fasting is taken out liver after one night and is prepared 5α-reductase, and carries out protein quantification by the BCA method of improvement, and operating procedure is carried out in strict accordance with test kit description.Quantification of protein standard curve is as figure below:
3.2 Establishing
Body series is optimized on original system basis.Utilize high-performance liquid chromatography to measure substrate testosterone surplus, then deduct the rear remaining testosterone amount of reaction by total testosterone amount of participating in reaction, obtain the testosterone amount that consumes in reaction system, and then calculate enzyme activity.
Chromatographic condition: luna C18 (2) posts (4.6x250mm, 59m); Column temperature: 40 DEG C; Sample size: 10uL; Flow velocity: lmL/min; Mobile phase: 70% methanol; Detect wavelength: 242nm.
3.2.1 testosterone standard curve is formulated
As Fig. 2, abscissa is the testosterone amount of 10uL, and vertical coordinate is peak area, and as can be seen from the figure testosterone amount and peak area are good linear relation.
3.2.25 5 alpha-reductases concentration is determined
As seen from Figure 3, along with raise its vigor of enzyme concentration strengthens, in the time that enzyme concentration reaches 8.675mg/mL, enzyme activity declines on the contrary, may be that too high enzyme concentration has suppressed due to the conversion of testosterone.
3.2.3 the impact of different concentration of substrate on enzyme activity
As shown in Figure 4, along with the increase enzyme activity of concentration of substrate raises, in the time that concentration of substrate is 2mg/mL, enzyme activity maximum.
3.2.4 the impact of the NADPH of variable concentrations on enzyme activity
As shown in Figure 5, along with the rising of NADPH concentration, enzyme activity also increases, and is not affecting under the prerequisite of result, considers to select the concentration of NADPH to be made as 5mg/mL from economic angle.
To sum up, determine that in reaction system, enzyme concentration is that 5.045mg/mL, substrate testosterone concentration are that 2mg/mL, NADPH concentration are 5mg/mL (enzyme power maximum).
3.3 finasterides suppress determination of activity to 5α-reductase
Finasteride is the common drug of clinical treatment prostatic hyperplasia, is effective 5α-reductase inhibitor.Under definite reaction condition, dehydrated alcohol is replaced with to finasteride, measure the inhibition activity of each concentration finasteride to 5α-reductase, then do a dehydrated alcohol reacting hole and a blank well (adding dichloromethane cessation reaction before adding enzyme).According to suppressing activity=(T finasteride-T reaction)/(T blank-T reaction) × 100%, calculates the IC that finasteride suppresses 5α-reductase 50value.The results are shown in Figure 6, calculated by Fig. 6, finasteride suppresses the IC of 5a-reductase 50for 275.7nM, close with bibliographical information.Can determine thus, the enzyme extract in female rats hepatomicrosome source has 5α-reductase activity, and the Drugs against benign prostate hyperplasia thing in-vitro screening method taking 5α-reductase as target of setting up with this is feasible, can be used for the screening of medicine.
4. mango aglycone and derivant thereof suppress active mensuration to 5α-reductase
Have bibliographical information chimonin inhibited to 5α-reductase, our early-stage Study result also shows that the bioavailability of mango aglycone is far away higher than chimonin, and is also starkly lower than chimonin by the synthetic cost of preparing mango aglycone.
By mango aglycone and the derivant thereof of 100%DMSO preparation variable concentrations, do a 100%DMSO reacting hole and a blank well (cessation reaction adds methylene chloride before enzyme-added).Mango aglycone and derivant thereof suppress activity=(T to 5α-reductase sample-T reaction)/(T blank-T reaction) * 100%.The results are shown in Figure 7-11, calculate the IC of mango aglycone and derivant thereof 50between 17.7-43.63uM, and the mango aglycone of variable concentrations and derivant thereof are linear dependence to the inhibition activity of 5α-reductase.
Embodiment 2: Testosterone Propionate is copied to drug action in the body of prostatic hyperplasia model mice and investigate
1. test material
1.1 animal
SPF level male ICR mouse, body weight 20-22g, animal housing of Kunming Medicine Group Stock Co., Ltd provides, credit number SCXK (Yunnan).
1.2 tested material
Mango aglycone, pale yellow powder, purity >98%, the academy of Kunming pharmacy group provides, lot number 20130903; Finasteride tablet (the accurate word H20070146 of traditional Chinese medicines), 5mg/ sheet, Hubei Shubang Pharmaceutical Co., Ltd., lot number: 0121001; Longbishu Jiaonang. (the accurate word Z10960007 of traditional Chinese medicines), 0.3g/ grain, Kedi Pharmaceutical Co., Ltd., Shijiazhuang, lot number: 111113; The suspension that is made into variable concentrations with pure water is for subsequent use.
1.3 reagent
Testosterone Propionate injection (the accurate word H12020531 of traditional Chinese medicines), 10mg/mL, Tianjin KingYork Amino Acid Co., Ltd., lot number 1202051; Mice androgen (T), estrogen (E2) test kit, R & D company, lot number 05/2013.
2. experimental technique
2.1 experimentation
Get 84 of 20-22g male mice in kunming, be divided at random 7 groups by body weight: normal control; Model contrast; Finasteride 1mg.kg -1; Longbishu Jiaonang. 0.45g.kg -1; Mango aglycone 60,30,15mg.kg -1; Every group 12.Except Normal group, each animal pattern is organized and presses 5mg.kg morning every day -1sc Testosterone Propionate, according to dosage distinguish gastric infusion afternoon, and model group gives normal saline, and volume is 20mL.kg -1; Continuous 21 days, weigh weekly 1 time.After last administration, water 12h is can't help in fasting, after weighing, gets blood, and separation of serum is pressed ELLISA kit method and measured T, E2 level in serum; De-cervical vertebra is put to death mice, takes out rapidly prostate and weighs, and calculates each group of mice prostate index (prostate index=prostate weight in wet base mg/ Mouse Weight g × 10).
2.2 date processing
Mean ± standard deviation for measurement data ( ) represent, variance is together with t inspection, and heterogeneity of variance t ' checks; Skewness distributes with non-ginseng rank test; P<0.05 has statistical significance,
P<0.01 has remarkable statistical significance.
3. experimental result
3.1 impacts on BPH Mouse Weight
From table 1, experimental session is respectively organized the sustainable growth of Mice Body weight average, model group with Normal group, each administration group compared with model group, the equal no significant difference of weight of mice.
The impact of table 1 on BPH Mouse Weight
Compared with model group: P > 0.05
3.2 impacts on BPH mice prostate weight in wet base and index
From table 2, model group mice prostate weight in wet base and index obviously raise, and difference highly significant compared with Normal group (P < 0.01) shows modeling success; Compared with model group, except the effect of Longbishu Jiaonang. approaches significant difference (P > 0.05), three dosage groups of mango aglycone and positive control finasteride group all can significantly reduce prostate weight in wet base and the index (P < 0.05/0.01) of model mice, and wherein the effect of three dosage groups of mango aglycone has doses dependency.
The impact of table 2 on BPH mice prostate weight in wet base and index
Compared with normal group: ▲ ▲p<0.01; Compared with model group:
*/**P<0.05/0.01
3.3 impacts on 5α-reductase activity in BPH mouse liver
From table 3, in the homogenate of model group mouse liver, the vigor of 5a-reductase, apparently higher than Normal group, shows that a large amount of exogenous androgen have induced the rising of the vigor of 5a-reductase; Except the effect of Longbishu Jiaonang. approaches (P > 0.05) significant difference, 5α-reductase vigor in three dosage treated animal liver homogenates of positive control finasteride and mango aglycone is starkly lower than model group (P < 0.05/0.01), consistent with in vitro tests result.
The impact of table 3 on 5a-reductase activity in BPH mouse liver
Compared with normal group: p<0.05; Compared with model group: * * P<0.01
3.4 impacts on female in BPH mice serum/androgen levels
From table 4, in model group mice serum, estrogen level and E2/T ratio are apparently higher than Normal group (P < 0.01/0.05), androgen levels only has rising trend (P > 0.05) than normal group, shows that BPH mice is with endocrine imbalance.Except finasteride, each administration group all can reduce animal pattern serum E2 level and E2/T ratio in various degree, and wherein mango aglycone three dosage have notable difference (P < 0.05/0.01) compared with matched group; Except finasteride, each administration group all can improve animal pattern serum T level (P > 0.05) in various degree, and wherein in mango aglycone, the effect of dosage approaches significant difference.
The impact of table-4 on hormonal readiness in BPH mice serum
Compared with normal group, ▲/▲ ▲p<0.05/0.01; Compared with model group, */* *p<0.05/0.01
4. brief summary
Testosterone is the main androgen in body, under 5α-reductase effect, becomes dihydrotestosterone, and the increase of intraprostatic DHT concentration can cause glandular hyperplasia.In addition, the disorderly theory of estrogen and androgen thinks that the rising of E/T ratio can cause prostatic hyperplasia.Prostate weight in wet base and prostate index can directly reflect the situation of prostatic hyperplasia.
The continuous 21 days exogenous Testosterone Propionate of subcutaneous injection of model mice, but the level of serum testosterone only has rising trend compared with normal group, and estrogen level and E2/T ratio significantly raise, point out a large amount of testosterones except being converted in prostate the DHT that causes glandular hyperplasia, some may be converted into E2 through the effect of aromatase.The E2 level of finasteride group is higher than model group, may select to suppress active relevant to the height of II type 5α-reductase with finasteride, finasteride reduces the generation of dihydrotestosterone by suppressing 5α-reductase, be converted into E2 because negative feedback regulates T by aromatase approach, and cause thus side effect features such as () feminizations of finasteride life-time service.Chimonin tuple E2 level and E2/T ratio are starkly lower than model group, and T level raises to some extent, different with the effect feature of finasteride, may be relevant with the multiple target effect of natural drug.
With reference to above-mentioned experimental technique, investigate drug action in the each derivant of mango aglycone of the present invention copies prostatic hyperplasia model mice body to Testosterone Propionate, result shows that it has the pharmacological action similar to mango aglycone.
Embodiment 3: its mouse oral gavage approach acute toxicity test
Prerun shows that the oral mango aglycone of mice cannot measure LD 50therefore, reflect the acute toxicity situation of this tested material with the maximum dosage-feeding of 2 gavages in a day.When test, animal fasting feedwater, after 8 hours, is chosen 40 of 19.5~21.9g persons, and male and female half and half, are divided into administration group and matched group at random by sex and body weight, each 10 of every group of male and female.Administration group mice gives the mango aglycone pastel of 0.27g/mL by the heap(ed) capacity per os gavage of 40mL/kg, rechallenge after the 6h of interval, and amounting to dosage is 21.6g/kg.d, matched group gives the pure water of same volume.As a result, two treated animal outward appearances, behavioral activity, the mental status, appetite, defecation, fur, the colour of skin and breathing etc. are showed no overt toxicity reaction generation.Continuous Observation 14 days, animal is healthy survival all, and body weight obviously increases, and compares no difference of science of statistics between group, the results are shown in Table 5.Put to death and dissect animal, the viscera tissues such as the perusal heart, liver, spleen, lung, kidney, also show no obvious abnormalities.
The observation of table 5 mango aglycone mouse stomach maximum dosage-feeding test body weight ( g)
Compared with matched group, p>0.05
In mango aglycone mice one day, the maximum dosage-feeding of gavage is 21.6g/kg, is equivalent to 1440 times of allogenic animal pharmacodynamics effective dose 15mg/kg, has no animal generation overt toxicity reaction and dead.
To sum up, mango aglycone inside and outside all has obvious inhibitory action to 5α-reductase, and can obviously reduce Testosterone Propionate and copy prostate weight in wet base and the index of benign prostatic hyperplasia model mice, obviously reduces the ratio of serum estradiol level and E/T.In the acute toxicity test of mice maximum dosage-feeding, have no overt toxicity reaction.The effect of mango aglycone Suppress hyperplasia of prostate is closely related, also relevant with the regulating action of Endocrine with inhibition 5α-reductase.Mango aglycone has treatment characteristic to the potential many target spots of prostatic hyperplasia and higher safety, and simple in structure, easily chemosynthesis, thereby there is higher clinical practice potential quality.
embodiment 4: 1,3,6,7-tetrem acyloxy mango aglycone soft capsule
Method for making: get mango aglycone, add in soybean oil, stir it is dissolved completely, compacting soft capsule, dry, make 1000, obtain the product that specification is 30mg.
embodiment 5: mango aglycone soft capsule
Method for making: get mango aglycone, add in soybean oil, stir it is dissolved completely, compacting soft capsule, dry, make 1000, obtain the product that specification is 200mg.
embodiment 6: 3-hydroxyl-1,6,7-triacetoxyl group mango aglycone soft capsule
Method for making: get mango aglycone, add in Oleum Arachidis hypogaeae semen, stir it is dissolved completely, compacting soft capsule, dry, make 1000, obtain the product that specification is 500mg.
embodiment 7: 1,3-dihydroxy-6,7-diacetoxy mango aglycone sheet
Method for making: material is crossed respectively to 100 mesh sieves, take material by recipe quantity, mix homogeneously, stirs soft material processed, 18-24 mesh sieve granulation, aeration-drying at 70 DEG C, tabletting, film coating, obtains the product that specification is 60mg.
embodiment 8: 6,7-dihydroxy-1,3-diacetoxy mango aglycone sheet
Method for making: material is crossed respectively to 100 mesh sieves, take material by recipe quantity, mix homogeneously, stirs soft material processed, 18-24 mesh sieve granulation, aeration-drying at 70 DEG C, tabletting, film coating, obtains the product that specification is 100mg.
embodiment 9: 1,3,6,7-tetrem acyloxy mango aglycone capsule
Method for making: material is crossed respectively to 100 mesh sieves, take material by recipe quantity, mix homogeneously, stirs soft material processed, 18-24 mesh sieve granulation, mix homogeneously, aeration-drying at 60 DEG C, fills in hard capsule and can obtain the product that specification is 300mg.
The above is only the preferred embodiment of the present invention; it should be pointed out that for those skilled in the art, under the premise without departing from the principles of the invention; can also make some improvements and modifications, these improvements and modifications also should be considered as protection scope of the present invention.

Claims (5)

1. the compound with following structural formula is expressed the application of the medicine of increase or the relevant disease of hyperactivity at preparation treatment and 5α-reductase,
Wherein, R 1, R 2, R 3, R 4for H or acetyl group.
2. application according to claim 1, is characterized in that, described is carcinoma of prostate, androgenetic alopecia, female hirsutism or acne to the disease that 5α-reductase expression increases or hyperactivity is relevant.
3. there is the compound of following structural formula in the application of preparing in the medicine for the treatment of prostatic hyperplasia,
Wherein, R 1, R 2, R 3, R 4for H or acetyl group.
4. application according to claim 3, is characterized in that, the effective dose of described compound is 10-1000mg/kg/d.
5. application according to claim 3, is characterized in that, described medicine is tablet, granule, capsule, pill, suspensoid or the injection that mango aglycone derivant adds pharmaceutically acceptable adjuvant and makes.
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