CN104013611B - 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 PDFInfo
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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
Technical field
The present invention relates to pharmaceutical technology field, and in particular to mango aglycone and its derivant are preparing Drugs against benign prostate hyperplasia
Application in thing.
Background technology
Benign prostatic hyperplasia (BPH), is a kind of progressive frequent micturition, dysuria occur and be because prostate is significantly increased
The middle-aging male commonly encountered diseases of feature.Epidemiological study shows that 40 years old former sickness rate of hyperplasia of prostate is very low, accounts within 50 years old
Sickness rate close 90% after 40%, 80 years old, during by 90 years old, almost 100% find prostatitis if carrying out prostata tissue and checking
Gland hypertrophy.With the aging of China human mortality, in recent years its sickness rate is in rising trend.
The therapeutic modality of prostatic hyperplasia is broadly divided into operative treatment and Drug therapy.Excision had once been considered as once
The prefered method of radical cure BPH, but the advanced age problem of patient often makes operative treatment have certain limitation again, easily cause it is various simultaneously
Disease is sent out, according to statistics postoperative complication about 15%, case fatality rate about 1%.There is research to point out, prostate can produce panimmunity ball egg
In vain, the polypeptide containing zinc with various antibacterial actions can be synthesized, with protection reproductive system antibacterial and the micro- life of other cause of diseases is exempted from
The Effects on local immunological functions of thing invasion and attack, should try one's best reservation.
Cause the Etiological of BPH relevant with the rising of dihydrotestosterone content in prostata tissue.5α-reductase in vivo
The reaction that testosterone (T) is reduced to dihydrotestosterone (DHT) can be catalyzed, suppressing the activity of 5α-reductase can reduce prostata tissue
The content of middle dihydrotestosterone.Research shows that the disease related to 5α-reductase expression or hyperactivity has prostatic hyperplasia, prostatitis
Adenocarcinoma, androgenetic alopecia, female hirsutism, acne (5 learn sparks etc. steroid 5α-reductase and the type of 5α-reductase 2 lack
Sunken disease progress, preclinical medicine and clinic, 2006,3:225.Li Yongfang etc. suppress the active component of 5A- reductases in plant
Progress, Chinese herbal medicine, 2006,11:1740).
In recent years, Drug therapy BPH is increasingly becoming main treatment meanss, mainly has on 5α-reductase inhibitor, α-kidney
Adrenoceptor antagonist, plant amedica and Chinese patent medicine.Alpha-blocking agent can block the contraction state of prostate smooth musculature cells, before mitigation
The urethral stricture obstruction of row gland hypertrophy patient；5 alpha reductase inhibitors, can suppress the conversion of testosterone in prostate to dihydrotestosterone,
So as to reduce the prostate volume of hypertrophy.Either suit the medicine to the illness, to because or therapeutic alliance, can in various degree recover prostatic hyperplasia
The urinary function of patient, improves its quality of life, but chemicalses life-time service has an obvious adverse reaction, and Chinese patent medicine preparation
Have that material base and effective ingredient be not clear, the present situation that unclear action target spot, quality control difficulties, curative effect are difficult to ensure that.
There are the antibacterials of data sheet express contract 80% and 60% anticarcinogen directly or indirectly from natural product, it is natural
Medicine is just becoming the important source of human treatment's drug development.Having not yet to see natural drug has substantially suppression to 5α-reductase
Act on and in the report of anti-prostatic hyperplasia application aspect.
The content of the invention
It is an object of the invention to provide the new application of natural drug mango aglycone and its derivant.
Research in recent years find, mango aglycone for chimonin active metabolite, with antioxidation, suppress PTP1B activity,
Multiple pharmacological effects such as blood sugar lowering, antitumor, uric acid resisting and gout, but mango aglycone content in plant is extremely low, merely according to
By plant extraction process it is difficult to meet needs, inventor's early stage is obtained a series of purity by synthetic>98% chimonin
First derivant, is buff powder, and structural formula is：
Wherein, R1、R2、R3、R4For H or acetyl group.
The present invention provides the compound with following structural formula and is preparing treatment with 5α-reductase expression or hyperactivity phase
The application of the medicine of the disease of pass,
Wherein, R1、R2、R3、R4For H or acetyl group.
The present invention has carried out inside and outside pharmacodynamic study to mango aglycone and its derivant.As a result show：Mango aglycone and
Its derivatives has different degrees of inhibitory activity to 5α-reductase, and its inhibitory activity to 5α-reductase linearly according to
Lai Xing；Continuous gavage is administered 21 days, and mango aglycone can substantially mitigate the prostatitis that Testosterone Propionate replicates prostatic hyperplasia model mice
5α-reductase activity in ratio, the reduction liver organization of E2 and E/T, shows that it can be effective in gland weight in wet base and index, reduction serum
Suppress 5α-reductase activity, the work with the treatment disease such as prostatic hyperplasia related to 5α-reductase expression or hyperactivity
With.
Preferably, the disease that expression is increased or hyperactivity is related to 5α-reductase is prostatic hyperplasia, prostatitis
Adenocarcinoma, androgenetic alopecia, female hirsutism or acne.
It is highly preferred that the effective dose of described compound is 10-1000mg/kg/d.
The experiment proves that mango aglycone does not show lethal toxicity, one day in Mouse Acute Toxicity experiment
The maximum tolerated dose of interior gastric infusion more than 21.6g/kg, equivalent to the 1440 of allogenic animal pharmacodynamicss effective dose 15mg/kg
Times.
Mango aglycone of the present invention and its derivant can directly be used alone, and can also be mutually combined application；Can be with other
Medicine includes that plant extract composition compound recipe form is used, it is also possible to make health product in a usual manner and food form is used；
Mango aglycone derivant of the present invention add tablet made by pharmaceutically acceptable adjuvant, granule, capsule, pill,
Suspensoid or injection are used.Mango aglycone and its derivant structure are simple, easy chemosynthesis, with higher clinical practice
Prospect.
Description of the drawings
Fig. 1 is the albumen of variable concentrations and the relation of absorbance；
The linear relationship of Fig. 2 difference testosterone amounts and peak area；
Impact of Fig. 3 difference enzyme concentrations to enzyme activity；
The impact of Fig. 4 difference testosterone concentrations and enzyme activity；
Impacts of the NADPH of Fig. 5 variable concentrations to enzyme activity；
Inhibitory action of Fig. 6 finasterides to 5α-reductase；
Inhibitory action of Fig. 7 mango aglycones to 5α-reductase；
Fig. 8 1- hydroxyl -3, inhibitory action of 6, the 7- triacetoxyl group mango aglycones to 5a- reductases；
Fig. 9 3- hydroxyl -1, inhibitory action of 6, the 7- triacetoxyl group mango aglycones to 5a- reductases；
Inhibitory action of Figure 10 1,3- dihydroxy -6,7- diacetoxies mango aglycones to 5a- reductases；
Inhibitory action of Figure 11 6,7- dihydroxy -1,3- diacetoxies mango aglycones to 5a- reductases.
Specific embodiment
The invention discloses the application of mango aglycone and derivant in Drugs against benign prostate hyperplasia thing is prepared, art technology
Personnel can use for reference present disclosure, be suitably modified technological parameter realization.Specifically, all similar replacements and change
Dynamic apparent to those skilled in the art, they are considered as being included in the present invention.The application of the present invention is
It is described by preferred embodiment, related personnel substantially can be in without departing from present invention, spirit and scope to herein
Described methods and applications are modified or suitably the technology of the present invention is realized and applied to change with combining.
In order that those skilled in the art more fully understands technical scheme, with reference to specific embodiment pair
The present invention is described in further detail.
Embodiment 1：The external inhibitory action to 5α-reductase
1st, experiment material
SD raettins, Kunming Medical University；Testosterone, Shanghai Yuan Ye bio tech ltd (20130409)；NADPH,
Sigma companies (Lot SLBC6718V)；Finasteride, Hubei Shubang Pharmaceutical Co., Ltd. (20121001)；Tris-base,
BIOSHARP companies (Amresco0497)；Sodium Chloride, Sheng Gong biotech firms (Lot3004B220)；DTT, sigma company (Lot
BCBK8875V)；Dehydrated alcohol, Yunnan Shan Dian pharmaceutcal corporation, Ltds (Lot LN70N21)；Dichloromethane, Tianjin wind ship chemistry
Reagent Science and Technology Ltd. (20100926)；Chromatograph methanol, Beijing lark prestige Science and Technology Ltd. (116481)；Mango aglycone；
1- hydroxyl -3,6,7- triacetoxyl group mango aglycones；3- hydroxyl -1,6,7- triacetoxyl group mango aglycones；1,3- dihydroxy -6,
7- diacetoxy mango aglycones；6,7- dihydroxy -1,3- diacetoxy mango aglycones, purity is all higher than 98%, Kunming system
Drug research institute of medicine group provides.
2. experimental apparatus
DHG-9245A electric drying oven with forced convections, Shanghai Yiheng Scientific Instruments Co., Ltd；Biofuge freezes high speed centrifugation
Machine, Thermo companies；E2695 high performance liquid chromatographs, Waters companies.
3. experiment content
3.1 protein quantification
Liver is taken out after the night of female sd inbred rats fasting one and prepares 5α-reductase, and albumen is carried out with the BCA methods of improvement and determined
Amount, operating procedure is carried out in strict accordance with kit specification.Quantification of protein standard curve below figure：
3.2 Establishing
Body series are optimized on the basis of original system.It is remaining substrate testosterone to be determined using high-performance liquid chromatography
Amount, then deduct remaining testosterone amount after reaction with the total testosterone amount for participating in reaction, that is, the testosterone amount consumed in reaction system is obtained,
And then calculate enzyme activity.
Chromatographic condition：Luna C18 (2) post (4.6x250mm, 59m)；Column temperature：40℃；Sample size：10uL；Flow velocity：lmL/
min；Mobile phase：70% methanol；Detection wavelength：242nm.
3.2.1 testosterone standard curve is formulated
Such as Fig. 2, abscissa is the testosterone amount of 10uL, and vertical coordinate is peak area, as can be seen from the figure testosterone amount and peak face
Product is in good linear relation.
3.2.25 5 alpha-reductases concentration determines
As seen from Figure 3, strengthen as enzyme concentration raises its vigor, when enzyme concentration reaches 8.675mg/mL, enzyme activity is anti-
And decline, it may be possible to too high enzyme concentration is inhibited caused by the conversion of testosterone.
3.2.3 impact of the different concentration of substrate to enzyme activity
As shown in figure 4, as the increase enzyme activity of concentration of substrate is raised, when concentration of substrate is 2mg/mL, enzyme activity is most
Greatly.
3.2.4 impacts of the NADPH of variable concentrations to enzyme activity
As shown in figure 5, with the rising of NADPH concentration, enzyme activity is also increased, on the premise of result is not affected,
Economically consider to select the concentration of NADPH to be set to 5mg/mL.
To sum up, determine that enzyme concentration is 5.045mg/mL in reaction system, substrate testosterone concentration is 2mg/mL, NADPH concentration
For 5mg/mL (enzyme power is maximum).
3.3 finasterides are determined to 5α-reductase inhibitory activity
Finasteride is the common drug of clinical treatment prostatic hyperplasia, is effective 5α-reductase inhibitor.It is determined that
Reaction condition under, dehydrated alcohol is replaced with into finasteride, determine each concentration finasteride and the suppression of 5α-reductase lived
Property, then do a dehydrated alcohol reacting hole and a blank well (add and add before enzyme dichloromethane terminating reaction).According to suppression
System activity=(TFinasteride-TReaction)/(TIt is blank-TReaction) × 100%, calculates the IC that finasteride suppresses 5α-reductase50Value.As a result
See Fig. 6, calculated by Fig. 6, finasteride suppresses the IC of 5a- reductases50It is close with document report for 275.7nM.Thus may be used
With determine, female rats hepatomicrosome source enzyme extract have 5α-reductase activity, with this set up with 5α-reductase
Drugs against benign prostate hyperplasia thing in-vitro screening method for target is feasible, can be used for the screening of medicine.
4. the measure of mango aglycone and its derivant to 5α-reductase inhibitory activity
There is document report chimonin inhibited to 5α-reductase, our early-stage Study result also indicates that Fructus Mangifera Indicae
The bioavailability of aglycon is significantly larger than chimonin, and is also significantly lower than chimonin by the cost of synthetically prepared mango aglycone.
The mango aglycone and its derivant of variable concentrations are prepared with 100%DMSO, a 100%DMSO reacting hole and one is
Individual blank well (added methylene chloride terminating reaction before enzyme-added).Mango aglycone and its derivant to 5α-reductase inhibitory activity=
(TSample-TReaction)/(TIt is blank-TReaction) * 100%.As a result see Fig. 7-11, calculate the IC of mango aglycone and its derivant50In 17.7-
Between 43.63uM, and inhibitory activity linear dependency of the mango aglycone and its derivant of variable concentrations to 5α-reductase.
Embodiment 2：The internal drug action that prostatic hyperplasia model mice is replicated to Testosterone Propionate is investigated
1. test material
1.1 animal
SPF level male ICR mouses, body weight 20-22g, animal housing of Kunming Medicine Group Stock Co., Ltd provides, licence
Number SCXK (Yunnan).
1.2 tested material
Mango aglycone, pale yellow powder, purity>98%, Kunming pharmacy group academy provides, lot number 20130903；It is non-
That male amine piece (Chinese medicines quasi-word H20070146), 5mg/ pieces, Hubei Shubang Pharmaceutical Co., Ltd., lot number：0121001；LONGBISHU glue
Capsule (Chinese medicines quasi-word Z10960007), 0.3g/ grains, Kedi Pharmaceutical Co., Ltd., Shijiazhuang, lot number：111113；It is made into not with pure water
Suspension with concentration is standby.
1.3 reagent
Testosterone Propionate injection (Chinese medicines quasi-word H12020531), 10mg/mL, Tianjin KingYork Amino Acid Co., Ltd., lot number
1202051；Mice androgen (T), estrogen (E2) test kit, R＆D companies, lot number 05/2013.
2. experimental technique
2.1 experimentation
20-22g male mice in kunming 84 is taken, by body weight 7 groups are randomly divided into：Normal control；Model comparison；Non- that hero
Amine 1mg.kg-1；Longbishu Jiaonang. 0.45g.kg-1；Mango aglycone 60,30,15mg.kg-1；12 per group.Except Normal group
Outward, each animal pattern group daily morning press 5mg.kg-1Sc Testosterone Propionate, afternoon according to dosage distinguishes gastric infusion, and model group gives
Normal saline, volume is 20mL.kg-1；Continuous 21 days, weigh weekly 1 time.Water 12h is can't help in fasting after last dose, weighs
After take blood, separate serum and press T, E2 level in ELLISA kit methods measure serum；De- cervical vertebra puts to death mice, before rapid taking-up
Row gland is weighed, and calculates each group mouse prostate index (prostate index=prostate wet weight mg/ Mouse Weight g × 10).
2.2 data processing
Measurement data with mean ± standard deviation () represent, variance is checked together with t, heterogeneity of variance t ' inspections；Partially
State is distributed with non-ginseng rank test；P<0.05 is statistically significant,
P<0.01 is statistically significant.
3. experimental result
The impact of 3.1 pairs of BPH Mouse Weights
From table 1, the equal sustainable growth of each group Mouse Weight during experiment, model group and Normal group, each administration group
Compared with model group, Mouse Weight increases equal no significant difference.
Impact of the table 1 to BPH Mouse Weights
Compared with model group：P ＞ 0.05
The impact of 3.2 pairs of BPH mouse prostates weight in wet bases and index
From table 2, model group mouse prostate weight in wet base and index are significantly raised, and difference is very compared with Normal group
Significantly (P ＜ 0.01), shows modeling success；Compared with model group, except the effect of Longbishu Jiaonang. close significant difference (P ＞
0.05) outward, three dosage groups of mango aglycone and positive control finasteride group can significantly reduce model mice prostate it is wet
Weight and index (P ＜ 0.05/0.01), the effect of wherein three dosage groups of mango aglycone has doses dependency.
Impact of the table 2 to BPH mouse prostates weight in wet base and index
Compared with normal group：▲▲P<0.01；Compared with model group：
*/**P<0.05/0.01
The impact of 5α-reductase activity in 3.3 pairs of BPH mouse livers
From table 3, the vigor of 5a- reductases shows apparently higher than Normal group in the homogenate of model group mouse liver
Rising of a large amount of exogenous androgen induction of the vigor of 5a- reductases；Except the close significant difference of the effect of Longbishu Jiaonang.
Outward (P ＞ 0.05), the 5α-reductase vigor in the three dosage group animal liverss homogenate of positive control finasteride and mango aglycone
It is consistent with vitro tests result significantly lower than model group (P ＜ 0.05/0.01).
Impact of the table 3 to 5a- reductase activities in BPH mouse livers
Compared with normal group：▲P<0.05；Compared with model group：**P<0.01
The impact of female/androgen levels in 3.4 pairs of BPH mice serums
From table 4, estrogen level and E2/T ratios are apparently higher than Normal group (P ＜ in model group mice serum
0.01/0.05), androgen levels only have rising trend (P ＞ 0.05) than normal group, show BPH mices with endocrine mistake
Adjust.In addition to finasteride, each administration group can in various degree reduce animal pattern blood serum E2 level and E2/T ratios, wherein Fructus Mangifera Indicae
The dosage of aglycon three has notable difference (P ＜ 0.05/0.01) compared with matched group；In addition to finasteride, each administration group can be different
Degree improves animal pattern serum T level (P ＞ 0.05), the close significant difference of effect of wherein mango aglycone middle dosage.
The impact of hormonal readiness in -4 pairs of BPH mice serums of table
Compared with normal group,▲/▲▲P<0.05/0.01；Compared with model group,*/**P<0.05/0.01
4. brief summary
Testosterone is internal chief androgen, and under 5α-reductase effect dihydrotestosterone is changed into, and intraprostatic DHT is dense
Degree increase can cause glandular hyperplasia.Additionally, estrogen and androgen disorder theory thinks that E/T ratios are raised can cause prostatic hyperplasia.Before
Prostate wet weigh and prostate index can directly reflect the situation of prostatic hyperplasia.
The exogenous Testosterone Propionate of the continuous 21 days subcutaneous injections of model mice, but the level of serum testosterone compared with normal group only
There is rising trend, and estrogen level and E2/T ratios are significantly raised, and are pointed out substantial amounts of testosterone to remove and are converted in prostate
Cause outside the DHT of glandular hyperplasia, the effect of some possible Jing aromatase is converted into E2.The E2 levels of finasteride group
Higher than model group, may be relevant to the high selection inhibitory activity of II type 5α-reductase with finasteride, finasteride is by suppressing
5α-reductase reduces the generation of dihydrotestosterone, because negative-feedback regu- lation T is converted into E2 by aromatase approach, and thus leads
Cause the side effect (feature such as feminization) of finasteride life-time service.Chimonin tuple E2 level and E2/T ratios are substantially low
In model group, and T levels have been raised, different with the action character of finasteride, may be with many targets of natural drug
Point effect is relevant.
With reference to above-mentioned experimental technique, investigate each derivant of mango aglycone of the present invention and prostate increasing is replicated to Testosterone Propionate
The internal drug action of raw model mice, as a 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 Mouse oral mango aglycone cannot measure LD50, therefore come anti-with the maximum dosage-feeding of 2 gavages in a day
Reflect the acute toxicity situation of the tested material.During test, after animal fasting is fed water 8 hours, 19.5～21.9g person 40 is chosen, it is female
Male half and half, administration group and matched group are randomly divided into by sex and body weight, every group of male and female are each 10.Administration group mice presses 40mL/kg
The oral gavage of maximum capacity give the mango aglycone pastel of 0.27g/mL, be administered again after the 6h of interval, equivalent dosage is
21.6g/kg.d, matched group gives the pure water of same volume.As a result, two groups of animal appearances, behavioral activity, the mental status, appetite, big
Urine, fur, the colour of skin and breathing etc. are showed no overt toxicity reaction to be occurred.Continuous Observation 14 days, animal all health survivals, body
Weight substantially increases, and no difference of science of statistics is compared between group, the results are shown in Table 5.Put to death and dissect animal, the perusal heart, liver, spleen, lung, kidney
Deng viscera tissue, also show no obvious abnormalities.
The test body weight observation of the mango aglycone mouse stomach maximum dosage-feeding of table 5 (g)
Compared with matched group, p>0.05
The maximum dosage-feeding of gavage is 21.6g/kg in mango aglycone mice one day, effective equivalent to allogenic animal pharmacodynamicss
1440 times of dosage 15mg/kg, have no that animal occurs overt toxicity reaction and death.
To sum up, mango aglycone inside and outside has obvious inhibiting effect to 5α-reductase, and can substantially reduce Testosterone Propionate
Replicate the prostate wet weight and index of benign prostatic hyperplasia model mice, hence it is evident that reduce the ratio of serum estrogen levels and E/T
Value.Have no that overt toxicity reacts in the acute toxicity test of mice maximum dosage-feeding.The work of mango aglycone Suppress hyperplasia of prostate
It is also relevant with the adjustment effect of Endocrine with closely related with suppression 5α-reductase.Mango aglycone has to prostatic hyperplasia
The treatment characteristic of potential Mutiple Targets and higher safety, and simple structure, easy chemosynthesis, thus with higher clinic
Using potential quality.
Embodiment 4：1,3,6,7- tetra- acetoxyl group mango aglycone soft capsule
Preparation method：Mango aglycone is taken, in adding to soybean oil, stirring is completely dissolved it, suppresses soft capsule, is dried, and makes
1000, obtain final product the product that specification is 30mg.
Embodiment 5：Mango aglycone soft capsule
Preparation method：Mango aglycone is taken, in adding to soybean oil, stirring is completely dissolved it, suppresses soft capsule, is dried, and makes
1000, obtain final product the product that specification is 200mg.
Embodiment 6：3- hydroxyl -1,6,7- triacetoxyl group mango aglycone soft capsules
Preparation method：Mango aglycone is taken, in adding to Oleum Arachidis hypogaeae semen, stirring is completely dissolved it, suppresses soft capsule, is dried, and makes
1000, obtain final product the product that specification is 500mg.
Embodiment 7：1,3- dihydroxy -6,7- diacetoxy mango aglycone pieces
Preparation method：Material is crossed respectively 100 mesh sieves, by recipe quantity material is weighed, mix homogeneously stirs soft material processed, 18-24 mesh
Sieve series grain, aeration-drying at 70 DEG C, tabletting, film coating obtains final product the product that specification is 60mg.
Embodiment 8：6,7- dihydroxy -1,3- diacetoxy mango aglycone pieces
Preparation method：Material is crossed respectively 100 mesh sieves, by recipe quantity material is weighed, mix homogeneously stirs soft material processed, 18-24 mesh
Sieve series grain, aeration-drying at 70 DEG C, tabletting, film coating obtains final product the product that specification is 100mg.
Embodiment 9：1,3,6,7- tetra- acetoxyl group mango aglycone capsule
Preparation method：Material is crossed respectively 100 mesh sieves, by recipe quantity material is weighed, mix homogeneously stirs soft material processed, 18-24 mesh
Sieve series grain, mix homogeneously, aeration-drying at 60 DEG C obtains final product the product that specification is 300mg by filling in hard capsule.
The above is only the preferred embodiment of the present invention, it is noted that for the ordinary skill people of the art
For member, under the premise without departing from the principles of the invention, some improvements and modifications can also be made, these improvements and modifications also should
It is considered as protection scope of the present invention.
Claims (3)
1. application of the compound with following structural formula in the medicine for preparing treatment prostatic hyperplasia,
Wherein, R1、R2、R3And R4For H.
2. application according to claim 1, it is characterised in that the effective dose of the compound is 10-1000mg/kg/
d。
3. application according to claim 1, it is characterised in that the medicine is：The compound is added and pharmaceutically can connect
Tablet, granule, capsule, pill, suspensoid or injection made by the adjuvant received.
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Non-Patent Citations (4)
| Title |
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| 5α-还原酶在相关疾病中的作用;潘继升等;《医学综述》;20110930;第17卷(第17期);2571-2573 * |
| Constance Bock 等.Mangiferin and hesperdin metabolites are absorbed from the gastrointestinal tract of pigs after oral ingestion of a Cyclopia genistoides (honeybush tea) extract.《Nutrition Research》.2008,(第28期),879-891. * |
| 汪洋等.hSRD5A2体外药物筛选新模型的建立及在筛选药物上的应用.《中国药房》.2012,第23卷(第31期),2902-2904. * |
| 第11期，2759-2763.芒果苷苷元研究进展.《时珍国医国药》.2013,第24卷(第11期),第11期，2759-2763. * |
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