CN1460482A - Medicine composite containing icaritin and demethylicaritin and its application - Google Patents
Medicine composite containing icaritin and demethylicaritin and its application Download PDFInfo
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- CN1460482A CN1460482A CN 03129242 CN03129242A CN1460482A CN 1460482 A CN1460482 A CN 1460482A CN 03129242 CN03129242 CN 03129242 CN 03129242 A CN03129242 A CN 03129242A CN 1460482 A CN1460482 A CN 1460482A
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Abstract
The present invention provides a medicine composition including icaritin and/or demethylicaritin as active component, medicinal carrier and/or excipient and having plant female hormone action, it can be used in the preparation of medicines for curing various diseases of hormone-dependend type cancers, cardiovascular diseases, after-menopausal osteoporosis, climacteric indisposition, senile dementia, hepatitis, diabetes and others, also can be used as precursor compound of the medicine.
Description
Technical field
The invention belongs to medical composition and its use, relate generally to the pharmaceutical composition of phytoestrogen sample effect, relate in particular to the pharmaceutical composition that contains 3,5,7-trihydroxy-2-(4-methoxy-phenyl)-8-(3-methyl-but-2-enyl)-chromen-4-one (Icaritin) and Desmethylicaritin 8-Prenylkaempferol (Desmethylicaritin), and in pharmaceutically purposes.
Background technology
Phytoestrogen (Phytoestrogens) is the natural plants chemical compound that a class has estrogenic activity, has antioxidation, angiogenesis inhibitor, effects such as anticancer differentiation, studies show that phytoestrogen is regulated by receptor and non-receptor is regulated approach (as free radical resisting, the regulatory enzyme activity, ion channel) to the hormonal dependent cancer, cardiovascular disease and postmenopausal osteoporosis and climacteric uncomfortable disease, old dementia early, the liver inflammation, hepatic fibrosis, diabetes, hyperlipidemia, immune system, diseases such as viral infection etc. have prevention and therapeutical effect preferably.
One, phytoestrogen and osteoporosis
Osteoporosis is a kind of general skeletal diseases, reduces with the bone amount, and the micro structure of bone is degenerated, and bone strength lowers, and fragility increases, and the susceptibility that causes fracturing increases the systemic skeletal diseases for feature.The osteosporosis resistant medicament that uses clinically can roughly be divided into three classes at present: (1) suppresses the bone resorption medicine: as estrogen, calcitonin, diphosphonate, activated vitamin D derivant etc.; (2) increase the bone formation medicine: as activated vitamin D derivant, fluoride, with voltinism hydrocortisone (androgen and derivant), progestogen, PTH fragment, growth hormone, skeletal growth factor (BGP, BMP etc.).(3) improve the bone mass medicine: as calcitonin, activated vitamin D derivant, PTH fragment, the second filial generation, third generation diphosphonate etc.Yet, take in vitamin D or novel vitamin D analogues and can prevent fracture still can't determine; Fluoride easily causes osteogenesis imperfecta; Prolonged application estrogen may cause the onset risk of breast carcinoma, carcinoma of endometrium etc. to increase.And phytoestrogen is a kind of natural selective estrogen receptor modulators, and it has estrogen and the effect of estrogen antagonist sample, as some phytoestrogen bone is shown estrogen-like effects, bone density improving, and mammary gland is had anti-proliferative effect.Its mechanism may be by the mechanism of estrogen receptor mediation or the mediation of non-estrogen receptor, promotes the formation of bone and the mineralising of bone, transmits by the intracellular calcium signal, causes apoptosis and suppresses the bone resorption of osteoclast, to bone performance protective effect.
Two, phytoestrogen and cardiovascular disease
Phytoestrogen helps reducing cardiovascular disease danger by the influence to many factors such as blood fat, platelet, vascular smooth muscles.The mechanism of phytoestrogen such as isoflavone blood fat reducing is by changing the quantity and the activity of ldl receptor; The approach of anti peroxidation of lipid realizes.Another important mechanisms of phytoestrogen is an anticoagulant.Williams etc. do experimentation with monkey, find that isoflavone can reduce platelet aggregation rate behind the collagen-induced platelet activation.Discharge vasoconstrictive materials such as 5-HT behind the platelet activation, velocity of blood flow is descended.Equally, Schoene etc. discover that behind the feeding isoflavone, the rat platelet volume obviously reduces, and are in and are difficult for state of activation.There is research to think that genistein has the protein tyrosine kinase inhibitor activity, can reduces tyrosine phosphorylation, suppress platelet activation and gathering, thereby suppress vasoconstriction and thrombosis.
Dubey etc. have studied the influence of going into aortic smooth muscle cell of phytoestrogen to In vitro culture, find that phytoestrogen can suppress the synthetic of smooth muscle cell migration, propagation and extracellular matrix that platelet protogrowth factor etc. causes, and suppress or the activated protein kinase activity of downward modulation mitogen, thereby suppress the formation of vascular remodeling and new intima, its mechanism of action may mediate by estrogen receptor.
Except that above-mentioned effect, phytoestrogen antianginal, ARR effect have obtained confirmation in animal model.Phytoestrogen also has calcium antagonism, promote the synthetic justacrine NO of endotheliocyte, bring high blood pressure down etc., and these all help preventing and treating cardiovascular disease.
With the Herba Epimedii is the Action Specification of the mind Yiganning capsule of main component, acts on the preventing and treating cardiovascular disease effect from the extract of medical material Herba Epimedii, but active ingredient wherein especially monomeric compound and mechanism of action are not bright.
Three, phytoestrogen and hormone-dependent tumor
Studies show that phytoestrogen can reduce the incidence rate of sex hormone dependent tumor, the effect of women's tumor prevention is mainly reflected in the adjusting estrogen metabolism before the menopause, reduces the generation of potential carcinogenic metabolite; Postmenopausal women's phytoestrogen is by estrogen metabolism product performance antitumor action, and showing has preventive effect to the estrogen-dependent tumor.At present phytoestrogen is used to prevent women with breast cancer etc. mainly as food additive, as the exploitation of medicine still in conceptual phase.
Herba Epimedii (Herba Epimedii) has another name called Herba Epimedii, ground drying nest for Berberidaceae (Berberbidaceae) Epimedium (Epimedium) various plants, effect with kidney invigorating and YANG supporting, strengthening the tendons and bones, expelling wind and removing dampness is usually used in treating diseases such as sexual impotence erectile problem, dribbling urination, weakness of the waist and knees and coronary heart disease, chronic bronchitis, neural decline and poliomyelitis.Modern pharmacological research proves that Herba Epimedii contains special chemical constituent and significant biological activity, is a kind of Chinese crude drug with extensive pharmacologically active, and the activity of having reported has:
1, androgen sample effect: the commodity Herba Epimedii extract is injected to male mice, can increase the weight of prostate, Seminal vesicle and levator ani, illustrates to have the effect of androgen sample.
2, cardiovascular effect: the Herba Epimedii soft extracts, 20% concentration 0.5ml injects side pipe, and the dirty coronary flow of guinea-pig heart is increased; Live part 25%0.3ml/ only makes mouse cardiac muscle right
86The picked-up of Rb increases; The 100%8mg/kg intravenous injection has protective effect to the myocardial ischemia that pituitrin causes.Herba Epimedii soft extracts 1g/kg or icariin 1mg/kg intravenous injection descend the Cor Leporis intraventricular pressure, and the intraventricular pressure climbing speed descends, expression has inhibition to ventricular systole, and arterial pressure descends, and pulse pressure difference and contraction pressure reduction all increase, show the reduction Peripheral resistance, lightening heart load.
3, bone matrix hyperplasia: with Embryo Gallus domesticus femur extracorporeal culture-ing, prove Herba Epimedii injection 1mg/ml (injection: culture medium=2: 100～3: 100) have the effect of promotion bone tissue growth under the dosage condition, its femur length, dry weight and
35S mixes intensity all greater than matched group.
4, to Immune Effects: 70% methanolic extract 200mg/kg of Herba Epimedii or 500mg/kg irritate stomach, can strengthen the phagocytic activity of reticuloendothelial system, and mice carbon clearance speed is quickened.
5, anti-" yang deficiency " and defying age: Herba Epimedii, Herba Cistanches mixture 0.5g/ only, to " yang deficiency " mice due to the hydroxyurea, can weight increase, increase the synthetic of liver, spleen DNA, the anti-time lengthening of freezing.Epimedium flavone 0.7g/kg irritates stomach, can significantly recover the propagation reflection of D-galactose mouse aging T and bone-marrow-derived lymphocyte, improve the activity of the total superoxide dismutase of mouse liver (SOD), reduce the formation of hepatic tissue lipid peroxide, reduce the heart, liver etc. and organize lipofuscin to form.
6, to the effect of platelet aggregation: Herba Epimedii decoct 25～100mg/ml, polysaccharide 2.5～7.5mg/ml and crude flavonoid powder in vitro tests have the inductive rat platelet aggregation of the ADP of promotion, and three 100mg/kg irritates stomach, also promotes the inductive rat platelet aggregation of ADP.
7, antiviral: commodity Herba Epimedii decoct has inhibitory action to poliomyelitis and other enterovirus.
But it is up to the present, less about the report of icariin monomer and derivatives active research thereof.
(Epimedium Icariine is to separate the natural product of purifying from Herba Epimedii EI) to icariin, is a monomeric compound, is the effective ingredient of Herba Epimedii.Also contain other chemical constituents such as 3,5,7-trihydroxy-2-(4-methoxy-phenyl)-8-(3-methyl-but-2-enyl)-chromen-4-one, Desmethylicaritin 8-Prenylkaempferol in addition, its chemical structural formula is:
Icariin R=CH
3, R1=-Rha, R2=-Glc
3,5,7-trihydroxy-2-(4-methoxy-phenyl)-8-(3-methyl-but-2-enyl)-chromen-4-one R=CH
3, R1=R2=H
Desmethylicaritin 8-Prenylkaempferol R=R1=R2=H
Up to the present, yet there are no and relevantly both at home and abroad report to 3,5,7-trihydroxy-2-(4-methoxy-phenyl)-8-(3-methyl-but-2-enyl)-chromen-4-one and Desmethylicaritin 8-Prenylkaempferol estrogen-like effects pharmacologically active and as the research of selective estrogen receptor modulators.
Summary of the invention
The purpose of this invention is to provide a kind of pharmaceutical composition with the effect of phytoestrogen sample, this pharmaceutical composition comprises as the 3,5,7-trihydroxy-2-(4-methoxy-phenyl)-8-(3-methyl-but-2-enyl)-chromen-4-one of active component and Desmethylicaritin 8-Prenylkaempferol and pharmaceutical carrier and excipient.
In the pharmaceutical composition of the present invention, 3,5,7-trihydroxy-2-(4-methoxy-phenyl)-8-(3-methyl-but-2-enyl)-chromen-4-one and Desmethylicaritin 8-Prenylkaempferol can use separately or use with combining form separately.
Pharmaceutical composition provided by the invention, its dosage form mainly comprise tablet, chewing agent, capsule, suspension liquor, solution etc.
That the preparation of pharmaceutical composition provided by the invention, its route of administration mainly comprise is oral, parenteral route, local approach.The parenteral administration preparation mainly comprises injection, inhalant, suppository, carrier targeting drug delivery system.Local administration preparation mainly comprises cream, ointment, patch, spray, subcutaneous implant.
Pharmaceutical composition provided by the invention is preparing as the application in the selective estrogen receptor modulators.
Pharmaceutical composition provided by the invention, the application in the medicine that preparation prevents or the treatment menopausal syndrome is relevant.
Pharmaceutical composition provided by the invention, at preparation control or prevention cardiovascular and cerebrovascular disease, the application in the protection cardiovascular function medicine.
Pharmaceutical composition provided by the invention at preparation prevention or treatment disease of hematopoietic system, comprises the application in aplastic anemia, myelocytic leukemia, lymphoid leukemia, the blood platelet reduction medicine.
Pharmaceutical composition provided by the invention is in the application that is used for preparing lead compound.
The purposes that contains these two compound compositions complete synthesis or that come through structural modification should be considered as identical with plant origin.
The present invention is from the many pharmacologically actives of Herba Epimedii, at cell, organize aspect and on the whole the phytoestrogen sample activity of 3,5,7-trihydroxy-2-(4-methoxy-phenyl)-8-(3-methyl-but-2-enyl)-chromen-4-one, Desmethylicaritin 8-Prenylkaempferol is proved.The present invention has following characteristics:
1. what the present invention relates to is the activity of Chinese medicine monomer, and component is clear and definite, offers reference for seeking material foundation of tcm, complete synthesis solution medicine source and the modernization of Chinese medicine.These two use of a compound complete synthesis or that come through structural modification should be considered as identical with plant origin.
2. shielded two the principal monomer chemical compounds of the present patent application---the phytoestrogen sample intreractive theory and the using value of 3,5,7-trihydroxy-2-(4-methoxy-phenyl)-8-(3-methyl-but-2-enyl)-chromen-4-one, Desmethylicaritin 8-Prenylkaempferol are remarkable.
Description of drawings
Fig. 1 is the aspect graph of estrogen sensitive cells strain MCF-7/BUS under different tester condition of culture.
Fig. 2 is icariin, 3,5,7-trihydroxy-2-(4-methoxy-phenyl)-8-(3-methyl-but-2-enyl)-chromen-4-one, the Desmethylicaritin 8-Prenylkaempferol dose-effect relationship figure to the influence of MCF-7 cell proliferation.
Fig. 3 is estrogen sensitive cells strain MCF-7/BUS rate of increase under different tester conditions.
The specific embodiment
The estrogenic activity of embodiment 1 3,5,7-trihydroxy-2-(4-methoxy-phenyl)-8-(3-methyl-but-2-enyl)-chromen-4-one, Desmethylicaritin 8-Prenylkaempferol
This experiment is biological test carrier with MCF-7 estrogen-dependent breast cancer cell, adopts classical E-SCREEN method (classical way of detection compound estrogenic activity) to measure its estrogenic activity.
The routine of A, MCF-7 breast cancer cell is cultivated
Condition of culture: the DMEM culture medium contains 5% hyclone, 37 ℃, cultivates in the 5%CO2 incubator.Changed liquid once in 2～3 days; Trypsinization when treating that cell proliferation to 70%～80% merges is gone down to posterity.
B, the preparation of removing the hormone human serum
5% activated carbon and 0.5% glucosan T-70 were hatched 18～24 hours under 4 ℃ of stirring conditions altogether, the active carbon (DCC) of centrifugal acquisition glucosan bag quilt, DCC is mixed with serum with 5% concentration, stirred 1 hour under 4 ℃ of conditions, the centrifugal 15min of 5000 * g, filtration sterilization can be removed hormone wherein.
C, E-SCREEN proliferation test
Be suspended in behind the MCF-7 cell dissociation in the conventional DMEM culture medium, with cell density is that 8000～10000/ml/ hole is inoculated in 24 orifice plates, conventional culture medium culturing (DMEM+5% hyclone) 48hr, treat its adherent back replacing no phenol red conditioned medium (do not have phenol red DMEM culture medium+5% and remove the hormone human serum), behind the pre-cultivation 48hr, change conditioned medium and add and tried thing.DMSO solvent control group (feminine gender), 1nM estradiol positive controls, icariin, 3,5,7-trihydroxy-2-(4-methoxy-phenyl)-8-(3-methyl-but-2-enyl)-chromen-4-one, each Concentraton gradient group of Desmethylicaritin 8-Prenylkaempferol are established in this experiment.Cultivate mtt assay survey cytoactive after 7 days.
D, result
Referring to Fig. 1, be that the MCF-7 cell is at negative (0.1%DMSO), positive control (0.1nM estradiol), tester (icariin, 3,5,7-trihydroxy-2-(4-methoxy-phenyl)-8-(3-methyl-but-2-enyl)-chromen-4-one, the methyl Herba Epimedii) 0.1 μ M, upgrowth situation (amplification 10 * 10) under the 1 μ M concentration conditions, as can be seen, it is more that negative control group MCF-7 cell is the cell of pyknosis circle, cell is in slow propagation or dead state, icariin (0.1 μ M, 1 μ M) group does not have obviously influence, and positive controls (0.1nM estradiol), 3,5,7-trihydroxy-2-(4-methoxy-phenyl)-8-(3-methyl-but-2-enyl)-chromen-4-one (0.1 μ M, 1 μ M), demethyl Herba Epimedii (0.1 μ M, 1 μ M) group MCF-7 cell becomes adherent stereo structure growth, molecular marker for increased proliferation.
The test result of E-SCREEN model (referring to Fig. 2, Fig. 3) shows that icariin there is no estrogen-like effects, 3,5,7-trihydroxy-2-(4-methoxy-phenyl)-8-(3-methyl-but-2-enyl)-chromen-4-one and Desmethylicaritin 8-Prenylkaempferol then can promote the propagation of MCF-7 cell significantly, showed stronger estrogenic activity, and become certain dose-effect relationship (to see Fig. 2, n=5).Compare with DMSO solvent control group, the maximum propagation multiple of 3,5,7-trihydroxy-2-(4-methoxy-phenyl)-8-(3-methyl-but-2-enyl)-chromen-4-one is 3.85 ± 0.26 times, and the maximum propagation multiple of Desmethylicaritin 8-Prenylkaempferol is 3.75 ± 0.25 times, approaches the short proliferation function that the 1nM estradiol produces.When 0.1nM, 3,5,7-trihydroxy-2-(4-methoxy-phenyl)-8-(3-methyl-but-2-enyl)-chromen-4-one and desmethylicaritin and negative control relatively have significant difference (P≤0.05), 1nM～10 each concentration of μ M and negative control more all have utmost point significant difference (P≤0.01), Fig. 3 is that (0.1nM-10 μ M) to the short proliferation function of MCF-7 cell relatively under the variable concentrations condition for icariin, 3,5,7-trihydroxy-2-(4-methoxy-phenyl)-8-(3-methyl-but-2-enyl)-chromen-4-one, Desmethylicaritin 8-Prenylkaempferol, positive control is the 1nM estradiol, n=5
*P＜0.05,
*P＜0.01vs 0.1%DMSO.
D, conclusion
Icariin does not have short proliferation function to the MCF-7 cell, and 3,5,7-trihydroxy-2-(4-methoxy-phenyl)-8-(3-methyl-but-2-enyl)-chromen-4-one and Desmethylicaritin 8-Prenylkaempferol then can promote the propagation of MCF-7 cell significantly, have estrogen-like effects.
Embodiment 2 3,5,7-trihydroxy-2-(4-methoxy-phenyl)-8-(3-methyl-but-2-enyl)-chromen-4-ones and Desmethylicaritin 8-Prenylkaempferol are used aspect protect against osteoporosis and menopausal syndrome
In view of the phytoestrogen sample activity of 3,5,7-trihydroxy-2-(4-methoxy-phenyl)-8-(3-methyl-but-2-enyl)-chromen-4-one and Desmethylicaritin 8-Prenylkaempferol, these two chemical compounds can be used as the active drug of prevention and treatment osteoporosis and menopausal syndrome and are developed.Similar on foundation: a, the phytoestrogen structure to endogenous estrogen, osseous tissue there is estrogen-like effects, Epidemiological study, animal experiment, in vitro tests and human trial find that phytoestrogen by promoting bone formation, suppressing bone resorption, plays an important role in the osteoporosis due to the control estrogen deficiency.More sophisticated phytoestrogen genistein of foreign study and daidzein are used for prevention and treatment osteoporosis and menopausal syndrome as food additive and ancillary drug; The analog ipriflavone (ipriflavone) that carries out the structure of modification exploitation based on the phytoestrogen structure extensively uses clinically as anti-osteoporotic.B, Herba Epimedii water extract have the promotion Oesteoblast growth, increase the effect of sclerotin calcification; Desmethylicaritin 8-Prenylkaempferol is a naturally occurring composition in the medical material Herba Epimedii, and 3,5,7-trihydroxy-2-(4-methoxy-phenyl)-8-(3-methyl-but-2-enyl)-chromen-4-one participates in the internal metabolism of icariin, and both probably are the real active substances of medical material Herba Epimedii.The embodiment of the invention 1 result supports this viewpoint, and the utmost point is hopeful to develop the natural drug that becomes osteoporosis.
Embodiment 3 substitutes the application of medicine as HRT
The purpose of postmenopausal women Hormone Replacement Therapy (HRT) is symptom, prevention of osteoporosis and the cardiovascular disease that control menopause causes.Have only the women of 35%-40% to accept HRT at present, and a lot of people can not adhere to using, its reason is that estrogen has many side effect as the HRT medicine, as breast carcinoma, the dangerous rising of carcinoma of endometrium, vaginal hemorrhage etc., and phytoestrogen much has the activity that selectivity is regulated estrogen receptor as natural product, show estrogen activity and estrogen antagonist sample activity simultaneously, if can antagonism mammary gland vagina etc. the estrogen receptor of tissue, and the estrogen receptor that exciting cardiovascular and skeleton etc. are located.Therefore show gratifying prospect in the research aspect cardiovascular protective effect, reduction blood cholesterol levels, control menopausal symptom and prevention of osteoporosis.
3,5,7-trihydroxy-2-(4-methoxy-phenyl)-8-(3-methyl-but-2-enyl)-chromen-4-one and Desmethylicaritin 8-Prenylkaempferol can be used as the flavonoid phytoestrogen and are developed, and may be used for the alternative medicine of estrogenic activity for the new selective estrogen receptor modulators of a class.
Embodiment 4 3,5,7-trihydroxy-2-(4-methoxy-phenyl)-8-(3-methyl-but-2-enyl)-chromen-4-ones and Desmethylicaritin 8-Prenylkaempferol are as the application of cardiovascular protector
Herba Epimedii has multiple pharmacologically active, is that the Chinese medicine preparation of main component has been used for prevention and treatment cardiovascular disease with the Herba Epimedii, but its complicated component, mechanism is not bright.
Desmethylicaritin 8-Prenylkaempferol is a naturally occurring composition in the medical material Herba Epimedii, and 3,5,7-trihydroxy-2-(4-methoxy-phenyl)-8-(3-methyl-but-2-enyl)-chromen-4-one participates in the internal metabolism of icariin, and both probably are the real active substances of medical material Herba Epimedii.And show stronger blood vessel dilating, antioxidant activity, and might be real active component in the body, the embodiment of the invention 1 result supports this viewpoint.In addition, the applicant still has result of study to show, icariin can significant inducing embryo stem cell directed differentiation be a myocardial cell, and prompting is to there being specific action myocardium biology; There are some researches show that simultaneously icariin can suppress blood vessel phosphate (PDE) activity, has vasorelaxation action.Therefore as the derivant of icariin, 3,5,7-trihydroxy-2-(4-methoxy-phenyl)-8-(3-methyl-but-2-enyl)-chromen-4-one and Desmethylicaritin 8-Prenylkaempferol very likely have equally or even stronger cardiovascular protection effect.
Embodiment 5
Strengthening yang and invigorating kidney effect prompting based on epimedium herb has androgen regulating action and assimilation, also has the androgen of plan treatment disease of hematopoietic system such as aplastic anemia, myelocytic leukemia, lymphoid leukemia, blood platelet reduction.
Embodiment 6
The formation of bibliographical information aglycon mainly is that metabolism forms under gastrointestinal tract environment, it is little to be used for non-oral medication 3,5,7-trihydroxy-2-(4-methoxy-phenyl)-8-(3-methyl-but-2-enyl)-chromen-4-one biological activity, the embodiment of the invention 1 result supports this viewpoint, so complete synthesis these two chemical compounds, both solve the medicine source, increased the biological activity of non-oral administration again.
Embodiment 7
3,5,7-trihydroxy-2-(4-methoxy-phenyl)-8-(3-methyl-but-2-enyl)-chromen-4-one and Desmethylicaritin 8-Prenylkaempferol are made the microsome drug-supplying system, as make specificity and effectiveness that liposome, nanoparticle drug-supplying system etc. can increase pharmaceutically-active targeting and effect.
Embodiment 8
Estrogenic activity and from then on extended many possible estrogen receptor adjustings or non-receptor adjusting pharmacologically active based on 3,5,7-trihydroxy-2-(4-methoxy-phenyl)-8-(3-methyl-but-2-enyl)-chromen-4-one, Desmethylicaritin 8-Prenylkaempferol, can be with 3,5,7-trihydroxy-2-(4-methoxy-phenyl)-8-(3-methyl-but-2-enyl)-chromen-4-one and Desmethylicaritin 8-Prenylkaempferol as the medicine main component, in order to the medicine of preparation prevention and treatment relevant disease.The partial reference document that the present invention relates to
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Need not further to elaborate, believe and adopt the disclosed content in front, those skilled in the art can use the present invention to greatest extent.All quote in this application as a reference at all documents that the present invention mentions, just quoted as a reference separately as each piece document.Should be understood that in addition those skilled in the art can make various changes or modifications the present invention after having read above-mentioned teachings of the present invention, these equivalent form of values fall within the application's appended claims institute restricted portion equally.
Claims (10)
1. pharmaceutical composition that contains 3,5,7-trihydroxy-2-(4-methoxy-phenyl)-8-(3-methyl-but-2-enyl)-chromen-4-one, Desmethylicaritin 8-Prenylkaempferol, it is characterized in that: this pharmaceutical composition comprises as the 3,5,7-trihydroxy-2-(4-methoxy-phenyl)-8-(3-methyl-but-2-enyl)-chromen-4-one of active component and/or Desmethylicaritin 8-Prenylkaempferol, pharmaceutical carrier and/or excipient.
2. pharmaceutical composition as claimed in claim 1 is characterized in that: its dosage form mainly comprises tablet, chewing agent, capsule, suspension liquor, solution.
3. pharmaceutical composition as claimed in claim 1 is characterized in that: its route of administration mainly comprises oral, parenteral route, local approach.
4. pharmaceutical composition as claimed in claim 3 is characterized in that: the parenteral administration preparation mainly comprises injection, inhalant, suppository, carrier targeting drug delivery system.
5. pharmaceutical composition as claimed in claim 3 is characterized in that: local administration preparation mainly comprises cream, ointment, patch, spray, subcutaneous implant.
6. pharmaceutical composition as claimed in claim 1 is characterized in that: preparing as the application in the selective estrogen receptor modulators.
7. pharmaceutical composition as claimed in claim 1 is characterized in that: the application in preparing prevention or the treatment medicine relevant with menopausal syndrome.
8. pharmaceutical composition as claimed in claim 1 is characterized in that: at preparation control cardiovascular and cerebrovascular disease, and the application in the protection cardiovascular function medicine.
9. pharmaceutical composition as claimed in claim 1 is characterized in that: the application in preparing prevention or treatment disease of hematopoietic system such as aplastic anemia, myelocytic leukemia, lymphoid leukemia, blood platelet reduction medicine.
10. pharmaceutical composition as claimed in claim 1 is characterized in that: the application in the preparation lead compound.
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