CN104173418B - The composition and purposes of the bark of eucommia and teasel root - Google Patents
The composition and purposes of the bark of eucommia and teasel root Download PDFInfo
- Publication number
- CN104173418B CN104173418B CN201410397179.9A CN201410397179A CN104173418B CN 104173418 B CN104173418 B CN 104173418B CN 201410397179 A CN201410397179 A CN 201410397179A CN 104173418 B CN104173418 B CN 104173418B
- Authority
- CN
- China
- Prior art keywords
- eucommia
- bark
- teasel root
- extract
- purposes
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Active
Links
Landscapes
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines Containing Plant Substances (AREA)
Abstract
The present invention relates to the composition comprising the bark of eucommia and teasel root and its treatment osteopathy, the purposes of post menopausal cognitive defect disease.The composition includes Chinese medicine teasel root and the bark of eucommia combines, including individually extracts extract obtained mixture comprising teasel root and the bark of eucommia, or extracts obtained extract jointly comprising both teasel root and the bark of eucommia.Said composition has the function that the good treatment disease.
Description
The application is the divisional application for the patent application of application number 201210250590.4 submitted on July 19th, 2012；And
It is required that the priority of the Chinese patent application for the application number 2011102134581 that on July 2011 applying date 28 submitted, its whole
Content is incorporated herein by reference.
Technical field
The present invention relates to technical field of traditional Chinese medicines, and in particular to a kind of composition comprising the bark of eucommia and teasel root, more particularly to
The composition of extract including Traditional Chinese medicine eucommia bark and teasel root.Said composition has preferable therapeutic action for osteoporosis.
Background technology
Osteoporosis (ostcoporosis, OP) is a kind of systemic osteopathy, is reduced with bone amount, the fine structure of bone moves back
Change, bone strength reduces, fragility increase causes fracture neurological susceptibility to increase the systemic skeleton lesion being characterized.
The beta estradiol of steroid hormone 17 (estradiol, E2) is many target tissue growths, differentiation and exercises biology
The key regulator of function.Epidemiological study finds that Pre-menopausal Women cardiovascular event is less than with age male, and is enclosing
Climacteric and postmenopausal women cardiovascular event occur to be higher than with age male, prompt estrogen to play in the process important
Effect.Increasing research is found in recent years, and estrogen effect is abnormal closely related with the pathologic process of many diseases, such as breast
Gland cancer, hypertension, atherosclerosis, osteoporosis etc..The HRT lowly used for estrogen level
(Hormone Replacement Therapy, HRT) turns into a kind of clinically important treatment means, past 20
In for many years, HRT is used for supplementing always the hyposecretion of postmenopausal women's estrogen, improves menopausal syndrome symptom, reduces the heart
The incidence of vascular diseases, pre- preventing bone rarefaction occur.American Women health association (Women ' s Health in 2003
Initiative, WHI) clinical research is found, although being reduced during the grand climacteric women HRT with coronary heart disease intervenes
The danger of osteoporosis and fracture, but increase breast cancer, the risk of carcinoma of endometrium, for this for HRT or E2 study into
For new focus.At the same time, people also are being directed to seeking estrogen replacement thing, and it is female sharp it is expected that this substitute can play
Protective effect of the element to systems such as angiocarpy, relieving menopausal syndrome, and can reduce the risk of tumour, and this kind of material is claimed
For SERM (selective estrogen receptor modulators, SERMs).
The biological function of estrogen is mainly to be realized by genome effect and Non-genomic responses.Genome effect
Mainly mediated by estrogen receptor alpha and β (ER α and ER β)：Estrogen combines with ER α (β), causes acceptor to become and is configured to dimerization
Body is straight with the estrogen response element (estrogen response element, ERE) of target gene regulatory region in nucleus
Binding is closed, and adjusts the transcription of the gene.Estrogen except by directly adjust target gene transcription play biological effect in addition to,
Some quick signal transductions, including generation second messenger, change ion channel can also be produced in the cell by membrane receptor
State, protein kinase-activated etc..The generation of these reactions is very fast, is generally so not enough within even several seconds in a few minutes
Produce in the time of new albumen and complete.This quick effect for not needing genetic transcription of estrogen is commonly known as " non-genomic
Group effect " or " fast reaction ".Certainly, fast reaction can not only cause ion channel to change, be quick anti-as NO releases
Should, effect signal can also be transmitted in nucleus by a series of signal transduction process, cause genes within cells to be expressed
Change, so as to produce long-term effect.
The biological effect of estrogen has Cell differentials simultaneously.ER α first and ER β are the products of different genes, ER α
The assignment of genes gene mapping is made up of 140kb bases in the areas of 6q 25.1 of No. 6 chromosome, encodes the protein of 595 amino acid；ER β bases
Because being positioned at the 14q 22-24 of No. 14 chromosome, it is made up of 40kb bases, encodes the protein of 530 amino acid, their sequence
Being listed in different regions has certain homology.Secondly ER α and ER β also have sizable difference in distribution and function,
In different organs, found using the method for in situ hybridization, the main high expression of ER α mRNA is in uterus, testis, pituitary gland
Deng the main high expression of, ER β mRNA in prostate, ovary, lung, blood vessel etc..In cardiovascular system, research finds vascular smooth muscle
(VSMC) ER β are mainly expressed, E2 reduces p42/44 and p38MAPK activity in VSMC, passes through ER β and suppresses smooth muscle cell increasing
Grow and migrate；And ER α are mainly expressed in endothelial cell (EC), E2 significantly induces p42/44 and p38MAPK activity in EC, leads to
Cross propagation, migration and eNOS expression that ER α promote EC.In Gegenbaur's cell, osteoclast, ER α and ER β have expression, still
Based on ER β.ER α and ER β also have expression in mononuclear macrophage (Raw264.7).This means that part of the same race with dividing
ER α and ER β hypotype of the cloth in different cells, which acts on, can show different bioactivity, and different parts and cognate receptor
Hypotype effect may also produce different pharmacological actions.The Cell differentials mechanism of estrogen effect ten is not distinguished still at present
Chu, so that occur some confusions in the research of estrogen and relevant disease relation, or even conflicting result.Can not be complete
Complete solution releases complicated clinical manifestation, pathological change and the different therapeutic responses to estrogen drugs of patient, make people couple with
The research of estrogen related significant disease pathogenesis and medicine is restricted.
Bone is estrogen target tissues, and estrogen can influence Bone m etabolism by number of ways.Gegenbaur's cell exist estrogen by
Body (estrogen receptor, ER), cell factor (IL-1, TNF, IL-6) acceptor, suppress releasing for cell factor when ER is activated
Put, after female hormone is reduced, inhibitory action weakens, and cell factor stimulates osteoclast, suppresses Gegenbaur's cell, causes bone amount to be lost
Lose.Complementing estrogen can effectively prevent the generation of PMO and its related fracture, but prolonged application increase uterus
The danger of endometrial carcinomas and breast cancer.
It is one of main pathological basis of osteoporosis that osteogenic ability, which declines, improves function of osteoblast and promotes bone shape
Treatment osteoporosis has direct significance in pairs, and effect of the research medicine to Gegenbaur's cell turns into treatment osteoporosis original new drug
The important content of exploitation.For alkaline phosphatase as a significant product for breaking up early stage in Bone m etabolism, it can be anti-from side
Effect of the medicine to Gegenbaur's cell is reflected, its active height can reflect the trend that corresponding cell converts to skeletonization direction.Bones morphology
Generation albumen -2 (bone morphogenetic protein-2, BMP-2) is important bon e formation regulatory factor, can be promoted
New bone formation, played a crucial role during osteoblast differentiation, it is possible to as the important target of osteoporosis protective agents
Point.Influenceed with reference to ERs activation, osteoblastic proliferation, alkaline phosphatase activities and expression of the material to BMP-2, can be with
It is expected that influence of the material to bone, so as to the research and development for treating osteoporosis original new drug.
Still the method for having new treatment osteoporosis is expected in this area.
The content of the invention
It is an object of the invention to provide a kind of method of new treatment osteoporosis.The present inventor uses Chinese medicine teasel root
Combined with the bark of eucommia, either individually extract extract obtained mixture using teasel root and the bark of eucommia or use teasel root and the bark of eucommia two
Person extracts obtained extract jointly, in accordance with the present invention it has now surprisingly been found that the two compatible use effect has reached collaboration better than being used alone
The therapeutic effect of synergy.The present invention is accomplished based on this discovery.
Therefore, first aspect present invention provides composition, it includes Chinese medicine teasel root and the bark of eucommia.
Composition according to a first aspect of the present invention, wherein both the teasel root and the bark of eucommia weight ratio are (0.01~100)：
1, or (0.02~50)：1, or (0.05~20)：1, or (0.1~10)：1, or (0.2~5)：1.
Composition according to a first aspect of the present invention, it is prepared by Chinese medicine teasel root and the bark of eucommia.In a reality
Apply in scheme, both the teasel root and the bark of eucommia weight ratio are (0.01~100)：1, or (0.02~50)：1, or (0.05~
20)：1, or (0.1~10)：1, or (0.2~5)：1.
Composition according to a first aspect of the present invention, it includes teasel root and the extract of the bark of eucommia.In one embodiment,
The extract is the respective extract that teasel root and the bark of eucommia are extracted to obtain respectively, then by medicinal material weight than being mixed to get.
In one embodiment, the extract is that teasel root and the bark of eucommia are extracted to obtain together.In one embodiment, described point
Obtained extract is extracted not or together, both medicinal material teasel root used and the bark of eucommia weight ratio are (0.01~100)：1, or
(0.02~50)：1, or (0.05~20)：1, or (0.1~10)：1, or (0.2~5)：1.
Composition according to a first aspect of the present invention, wherein the Radix Dipsaci extract is carried by using water or hydrous ethanol
Take, then be optionally concentrated to give with after alkali process and/or macroporous resin treatment.In one embodiment, the aqueous second
Alcohol is 30%~95% ethanol, preferably 50%~90% ethanol.
Composition according to a first aspect of the present invention, wherein the eucommia ulmoides extracts are by after water or hydrous ethanol extraction
It is concentrated to give.In one embodiment, the hydrous ethanol is 30%~95% ethanol, preferably 50%~90% ethanol,
It is preferred that 50%~80% ethanol, preferably 60%~80% ethanol.
Composition according to a first aspect of the present invention, wherein both the teasel root and the bark of eucommia are extracted together obtains extract.
In one embodiment, weight ratio both medicinal material teasel root used in the extract and the bark of eucommia is (0.01~100)：1, or
(0.02~50)：1, or (0.05~20)：1, or (0.1~10)：1, or (0.2~5)：1.In an embodiment
In, the extract is concentrated to give after both teasel root and the bark of eucommia one reinstates water or hydrous ethanol extraction.In an embodiment party
In case, the extract is that both teasel root and the bark of eucommia one reinstates water or hydrous ethanol extraction, then optionally with alkali process and/or greatly
After the resin treatment of hole, it is concentrated to give.In one embodiment, the hydrous ethanol is 30%~95% ethanol, preferably
50%~90% ethanol.
Composition according to a first aspect of the present invention, wherein being selected from following material comprising at least one：Wei rock celestial being saponin(es
A, 3-O-a-L- arabopyranoses-oleanolic acid -28-O- β-D- glucopyranoses-(1 → 6)-β-D- glucopyranosides,
Loganin (Loganin), split loganin glycosides, triplostoside A, Geniposide, geniposide, Geniposidic acid, white birch
Resin acid, aucubin, Pinoresinol diglucoside, syringaresinol diglucoside, rosin spirit list glucoside, syringaresinol
Single glucoside, wogonin, Chiba element A, baicalein, dihydrochalcone 3-O- β-D-Glucose glycosides, α-oxygen-β-D- grape pyrroles
Mutter glycosyl -4,2 ', 4 '-trihydroxy dihydrochalcone, chlorogenic acid, akebiasaponin D.Composition according to a first aspect of the present invention,
Wherein following material is selected from comprising at least one：Wei rock celestial beings saponin A, 3-O-a-L- arabopyranoses-oleanolic acid -28-
O- β-D- glucopyranoses-(1 → 6)-β-D- glucopyranosides, loganin (Loganin), split loganin glycosides,
Triplostoside A, Geniposide, geniposide, Geniposidic acid, betulic acid, aucubin, rosin spirit glucosulfone
Glycosides, syringaresinol diglucoside, rosin spirit list glucoside, syringaresinol list glucoside, wogonin, Chiba element A, Huang
A kind of reed mentioned in ancient books element, dihydrochalcone 3-O- β-D-Glucose glycosides, α-oxygen-β-D- glucopyanosyls base -4,2 ', 4 '-trihydroxy dihydro looks into ear
Ketone, chlorogenic acid, akebiasaponin D, and when their more than two kinds be present, their weight rates arbitrarily between the two are
0.0001~10000：1.
Second aspect of the present invention provides composition described in first aspect present invention and prepared for treating and/or preventing bone
Purposes in the medicine of matter osteoporosis.
Second aspect of the present invention additionally provides composition described in first aspect present invention and prepared for treating and/or preventing
Purposes in the medicine of osteopathy.
Second aspect of the present invention additionally provides composition described in first aspect present invention and prepared for treating and/or preventing
Purposes in the medicine of post menopausal cognitive defect disease.
Third aspect present invention provides a kind of pharmaceutical composition, wherein comprising composition described in first aspect present invention,
And pharmaceutically acceptable carrier.
Pharmaceutical composition according to a third aspect of the present invention, wherein being selected from following material comprising at least one：Wei rocks are celestial
Saponin A, 3-O-a-L- arabopyranoses-oleanolic acid -28-O- β-D- glucopyranoses-(1 → 6)-β-D- glucopyranoses
Glycosides, loganin (Loganin), split loganin glycosides, be triplostoside A, Geniposide, geniposide, Geniposidic acid, white
Pine gum acid, aucubin, Pinoresinol diglucoside, syringaresinol diglucoside, rosin spirit list glucoside, cloves fat
The single glucoside of element, wogonin, Chiba element A, baicalein, dihydrochalcone 3-O- β-D-Glucose glycosides, α-oxygen-β-D- grapes
Pyranose -4,2 ', 4 '-trihydroxy dihydrochalcone, chlorogenic acid, akebiasaponin D.
Pharmaceutical composition according to a third aspect of the present invention, wherein being selected from following material comprising at least one：Wei rocks are celestial
Saponin A, 3-O-a-L- arabopyranoses-oleanolic acid -28-O- β-D- glucopyranoses-(1 → 6)-β-D- glucopyranoses
Glycosides, loganin (Loganin), split loganin glycosides, be triplostoside A, Geniposide, geniposide, Geniposidic acid, white
Pine gum acid, aucubin, Pinoresinol diglucoside, syringaresinol diglucoside, rosin spirit list glucoside, cloves fat
The single glucoside of element, wogonin, Chiba element A, baicalein, dihydrochalcone 3-O- β-D-Glucose glycosides, α-oxygen-β-D- grapes
Pyranose -4,2 ', 4 '-trihydroxy dihydrochalcone, chlorogenic acid, akebiasaponin D, and work as and their more than two kinds be present
When, their weight rates arbitrarily between the two are 0.0001~10000：1.
Pharmaceutical composition according to a third aspect of the present invention, its be for treat and/or pre- anti-osteoporosis, osteopathy,
The medicine of post menopausal cognitive defect disease.
Pharmaceutical composition according to a third aspect of the present invention, it is in tablet, capsule, soft capsule, pill, externally applied drug
The forms such as agent, ejection preparation.
Embodiment
A, teasel root part
Teasel root example 1：The preparation of Radix Dipsaci extract and assay
Preparation method：
Step (i) takes 10 kilograms of teasel root medicinal materials (being purchased from Hebei Anguo Qi Xin Chinese medicinal granule medicine materical crude slice Co., Ltd) to be ground into slightly
Powder (is not added with screen cloth), is extracted with 10 times of 70% ethanol of amount, recovery ethanol obtains medicinal extract；
Step (ii) takes medicinal extract aqueous solution sodium hydroxide (add to aqueous phase amount 2%) obtained by step (i) to handle 2 at 60 DEG C
Hour, add appropriate hydrochloric acid to neutralize；
Step (iii) makes above-mentioned neutralizer cross the separation of D101 macroreticular resins, 50% ethanol elution, and eluent is dried, and is
The Radix Dipsaci extract of the present invention.
Through HPLC methods determine, wherein comprising 12.6% compound 1., 3.6% compound 2., 4.2% compound 3., 4.3%
Compound 4. and 3.5% compound 5..Wherein compound be 1. Wei rock celestial beings saponin A, compound be 2. 3-O-a-L- pyrans I
3. primary sugar-oleanolic acid -28-O- β-D- glucopyranoses-(1 → 6)-β-D- glucopyranosides, compound are loganin
(Loganin), 4. 5. compound is triplostoside A to split loganin glycosides, compound.
Teasel root example 2：The preparation of Radix Dipsaci extract and assay
Preparation method：
Step (i) takes 1 kilogram of teasel root medicinal material (being purchased from Hebei Anguo Qi Xin Chinese medicinal granule medicine materical crude slice Co., Ltd) to be ground into slightly
Powder (is not added with screen cloth), is extracted with 10 times of 60% ethanol of amount, recovery ethanol obtains medicinal extract；
Step (ii) takes medicinal extract aqueous solution sodium hydroxide (add to aqueous phase amount 2%) obtained by step (i) to handle 2 at 60 DEG C
Hour, add appropriate hydrochloric acid to neutralize；
Step (iii) makes above-mentioned neutralizer cross the separation of D101 macroreticular resins, 80% ethanol elution, and eluent is dried, and is
The Radix Dipsaci extract of the present invention.
Through HPLC methods determine, wherein comprising 9.8% compound 1., 3.7% compound 2., 2.9% compound 3., 3.4%
Compound 4. and 6.1% compound 5..
Teasel root example 3：The preparation of Radix Dipsaci extract and assay
Preparation method：
Step (i) takes 10 kilograms of teasel root medicinal materials (being purchased from Hebei Anguo Qi Xin Chinese medicinal granule medicine materical crude slice Co., Ltd) to be ground into slightly
Powder (is not added with screen cloth), is extracted with 10 times of 80% ethanol of amount, recovery ethanol obtains medicinal extract；
The medicinal extract is added suitable quantity of water to disperse by step (ii), then is extracted with ethyl acetate, and obtains ethyl acetate portion；
Step (iii) extraction gained aqueous phase sodium hydroxide (add to aqueous phase amount 2%) is handled 2 hours at 60 DEG C, is added suitable
Hydrochloric acid is measured to neutralize；
Step (iv) makes above-mentioned neutralizer cross the separation of D101 macroreticular resins, successively with 20% ethanol, 50% ethanol, 80% second
Alcohol elutes, and takes 80% ethanol elution fraction, dries, and is the Radix Dipsaci extract of the present invention.
Through HPLC methods determine, wherein comprising 17.6% compound 1., 6.6% compound 2., 9.2% compound 3.,
14.7% compound 4. and 8.3% compound 5..
Teasel root example 4：The preparation of Radix Dipsaci extract and assay
Preparation method substantially refers to extract example 3, is a difference in that step (i) 10 times of 50% ethanol of amount, step
(iii) handled 5 hours at 50 DEG C with potassium hydroxide (add to aqueous phase amount 1%), step (iv) D201 macroreticular resins and successively
With 15% ethanol, 55% ethanol, 75% ethanol elution.75% ethanol elution level lease making is dried, and produces Radix Dipsaci extract of the present invention.
Through HPLC methods determine, wherein comprising 15.4% compound 1., 7.2% compound 2., 3.1% compound 3., 4.7%
Compound 4. and 7.4% compound 5..
Teasel root example 5：The preparation of Radix Dipsaci extract and assay
Preparation method substantially refers to extract example 1, is a difference in that step (i) 10 times of 90% ethanol of amount, step
(iii) handled 2 hours at 80 DEG C with sodium acid carbonate (add to aqueous phase amount 5%), step (iv) AB-8 macroreticular resins and successively
With 25% ethanol, 85% ethanol elution.85% ethanol elution level lease making is dried, and is produced the present invention and is carried Radix Dipsaci extract.
Through HPLC methods determine, wherein comprising 16.3% compound 1., 5.6% compound 2., 7.2% compound 3.,
11.8% compound 4. and 6.9% compound 5..
Teasel root example 6：The preparation of Radix Dipsaci extract and assay
1000g teasel root medicinal materials are weighed, screen cloth is not added with and crosses pulverizer, 80% ethanol extracts three times, each 2h, and 10 times of amounts are molten
Agent, merge extract solution, recovery ethanol is concentrated into the greatest extent, is dried in vacuo to obtain Radix Dipsaci extract.HPLC assays contain 9.8% akebi
Saponin D, 1.2% compound is 1..
Teasel root example 7：The preparation of Radix Dipsaci extract and assay
1000g teasel root medicinal materials are weighed, screen cloth is not added with and crosses pulverizer, 50% ethanol extracts three times, each 2h, and 10 times of amounts are molten
Agent, merge extract solution, recovery ethanol is concentrated into the greatest extent, is dried in vacuo to obtain Radix Dipsaci extract.HPLC assays contain 7.8% akebi
Saponin D, 0.82% compound is 1..
Teasel root example 8：The preparation of monomeric compound
The gained Radix Dipsaci extract of teasel root example 1 above is taken, using preparation HPLC method and with reference to measure extractive content above
HPLC methods, respectively be made compound 1., compound 2., compound 3., compound 4. with compound 5..Five kinds of compounds
Purity is respectively 98.8%, 99.8%, 97.3%, 97.8% and 99.1%.
Teasel root example 9：The sign of monomeric compound
The Institute of Analysis of structural identification commission University Of Tianjin of each compound is detected, as a result as follows：
1. compound, is identified as Wei rock celestial beings saponin A (cauloside A), white powder (acetone), mp 239-241
DEG C, it is soluble in acetone and methanol, 1H-NMR (pyridine-d5) δ:5.47 (1H, brs, H-12), 4.99 (1H, d, J=8Hz, H-
1′),1.22、1.02、0.99、0.93、0.92、0.91(3H,s,6×CH3)；13C-NMRδ:38.8(C-1),26.1(C-2),
82.0(C-3),43.5(C-4),47.6(C-5),18.2(C-6),32.9(C-7),39.8(C-8),48.2(C-9),37.0(C-
10),23.7(C-11),122.6(C-12),144.9(C-13),42.2(C-13),28.3(C-14),28.3(C-15),23.9
(C-16),46.7(C-17),42.0(C-18),46.5(C-19),30.9(C-20),34.2(C-21),33.2(C-22),64.5
(C-23),13.6(C-24),16.1(C-25),17.5(C-26),26.2(C-27),180.3(C-28),33.2(C-29),
23.6(C-30),106.6(C-1′),73.1(C-2′),74.7(C-3′),69.6(C-4′),66.9(C-5′).Above physics and chemistry number
According to and spectral data and document it is basically identical.Structure is as follows.
Wherein R1=a-L-Ara；R2=H；R3=CH2OH。
2. compound, is identified as 3-O-a-L- arabopyranoses-oleanolic acid -28-O- β-D- glucopyranoses-(1
→ 6)-β-D- glucopyranosides, white needle-like crystals (methanol), mp 227-230 DEG C, are soluble in methanol, insoluble in chloroform and
Acetone, 1H-NMR (pyridine-d5) δ:6.30 (1H, d, J=8.5Hz, H-1 '), 5.41 (1H, brs, H-12), 4.95 (1H, d, J
=7.0Hz, H-1 "), 1.16,1.10,0.94,0.90,0.87,0.85 (3H, s, 6 × CH3)；13C-NMRδ:39.1(C-1),
26.4(C-2),17.9(C-3),43.8(C-4),47.9(C-5),18.5(C-6),33.4(C-7),40.3(C-8),48.5(C-
9),37.2(C-10),24.2(C-11),123.2(C-12),144.4(C-13),42.4(C-14),28.6(C-15),23.7
(C-16),47.3(C-17),42.0(C-18),28.6(C-15),23.7(C-16),47.3(C-17),42.0(C-18),46.5
(C-19),31.1(C-20),34.3(C-21),32.8(C-22),64.8(C-23),13.9(C-24),16.5(C-25),17.9
(C-26),26.4(C-27),176.8(C-28),33.1(C-29),24.0(C-30),107.0(C-1′),73.4(C-2′),
75.0(C-3′),70.0(C-4′),67.3(C-5′),96.0(C-1″),74.4(C-2″),79.6(C-3″),71.4(C-4″),
79.2(C-5″),62.5(C-6″).Wave Spectrum and 1H-NMR the and 13C-NMR data in document are basically identical, and its structure is as follows：
Wherein：R1=a-L-Ara；R2=β-D-Glc (1-6) β-D-Glc；R3=H.
3. compound, is identified as loganin (Loganin), pale yellow powder, is dissolved in methanol.1H-NMR(CD3OD)
δ:5.22 (1H, d, J=4.0Hz, H-1), 7.33 (1H, d, J=1.0Hz, H-3), 1.04 (3H, d, J=7.0Hz, H-10),
3.63(3H,s,OCH3)；4.59 (1H, d, J=8.0Hz, H-1 ')；13C-NMR(CD3OD)δ:97.8(C-1),150.9(C-
3),112.8(C-4),31.0(C-5),41.5(C-6),73.9(C-7),41.0(C-8),45.3(C-9),12.3(C-10),
168.3(C-11),50.5(C-12),98.8(C-1′),73.5(C-2′),77.2(C-3′),70.4(C-4′),76.8(C-
5′),61.6(C-6′).Wave Spectrum and 1H-NMR the and 13C-NMR data in document are basically identical, and its structure is as follows：
4. compound, is identified as following structural formula, to split loganin glycosides,
White, needle-shaped crystals (methanol), Molish reactions are aobvious positive, and sugar moieties are examined to know through thin-layer chromatography and proved after sour water solution
Only contain D-Glucose.1H-NMR(CD3OD):7.59 (1H, s, H-3), 5.79 (1H, br.s, H-7), 5.16 (1H, d, J=
7.8Hz, H-1), 4.70 (1H, d, J=8.0Hz, H-1 '), 4.19 (2H, q, H-10), 3.70 (3H, s, H-12), 2.70 (2H,
T, J=16.0Hz, H-6), 2.10 (1H, q, H-5).13C-NMR(CD3OD):98.1(C-1),153.9(C-3),106.1(C-
4),28.5(C-5),25.9(C-6),69.7(C-7),133.3(C-8),43.8(C-9),120.8(C-10),168.5(C-
11),99.8(C-1′),74.8(C-2′),78.4(C-3′),71.6(C-4′),77.9(C-5′),62.7(C-6′).Manage above
Change data and spectral data is consistent with document.
5. compound, is identified as triplostoside A, white powder, is dissolved in methanol.1H-NMR(CD3OD)δ：It is single
First A 5.47 (1H, d, J=5.5Hz, H-1), 7.39 (1H, s, H-3), 2.86 (1H, brq, J=7.0Hz, H-5), 1.66-
1.73(1H,m,H-6)；1.98-2.05 (1H, m, H-6), 4.46 (1H, dd, J=4.5Hz, H-7) 5.65-5.71 (1H, m, H-
8), 2.61-2.65 (1H, m, H-9), 4.46 (1H, d, J=7.0, H-1 '), 3.30 (6H, s, 2 × OCH3)；Unit B 5.25
(1H, d, J=4.5Hz, H-1), 7.37 (1H, s, H-3), 3.10 (1H, dd, J=4.0,8.4Hz, H-5), 1.59-1.67 (1H,
m,H-6)；2.00-2.07 (1H, m, H-6), 4.46 (1H, dd, J=4.4, H-7), 4.46 (1H, d, J=6.8, H-1 ') 3.63
(3H,s,OCH3)；13C-NMR(CD3OD)δ：Unit A 97.9 (C-1), 153.3 (C-3), 113.3 (C-4), 29.5 (C-5),
33.3(C-6),104.3(C-7),135.9(C-8),45.4(C-9),119.9(C-10),169.4(C-11),53.7(OCH3),
52.8(OCH3),100.1(C-1′),74.7(C-2′),78.0(C-3′),71.6(C-4′),78.4(C-5′),62.8(C-
6′)；Unit B 97.5 (C-1), 152.6 (C-3), 112.0 (C-4), 32.6 (C-5), 40.3 (C-6), 78.4 (C-7), 41.0
(C-8),47.1(C-9),13.9(C-10),168.3(C-11),51.8(OCH3),100.0(C-1′),74.6(C-2′),78.0
(C-3′),71.5(C-4′),78.4(C-5′),62.7(C-6′).Wave Spectrum and 1H-NMR the and 13C-NMR data bases in document
This is consistent, and triplostoside A structure is as follows：
Wherein it is unit A on the left of vertical line, is unit B on the right side of vertical line.
B, bark of eucommia part
Bark of eucommia example 1：The preparation of eucommia ulmoides extracts and assay
Eucommia ulmoides 500g, add the extraction of the alcohol refluxs of 5000ml 70% twice, 2 hours every time, merge extract solution filtering
After be concentrated into the greatest extent, be dried in vacuo to obtain eucommia ulmoides extracts.
After testing, the amount of the gentle geniposide of extract Zhong jing Buddhist nun is respectively 0.214%, 0.488%.
In addition after testing, the amount for finding following material in the extract is Geniposidic acid 0.925%, chlorogenic acid
0.302%, Pinoresinol diglucoside 0.99%, syringaresinol diglucoside 0.34%.
Bark of eucommia example 2：The preparation of eucommia ulmoides extracts and assay
Eucommia ulmoides 500g, add the extraction of the alcohol refluxs of 5000ml 70% twice, 2 hours every time, merge extract solution filtering
After be concentrated into the greatest extent, be then divided into two parts, extracted respectively with ethyl acetate and n-butanol, dry, obtain two kinds of extracts
Respectively as the eucommia ulmoides extracts of the present invention.
After testing, in the extract of ethyl acetate extraction, the amount of Geniposide and geniposide is respectively 1.14%,
12.38%；In the extract of extracting n-butyl alcohol, the amount of Geniposide and geniposide is respectively 9.4%, 0.89%.
In addition after testing, respectively 0.41~6.7% following material is contained in both the above extract：Geniposide
Acid, chlorogenic acid, Pinoresinol diglucoside, syringaresinol diglucoside.
Bark of eucommia example 3：The preparation of eucommia ulmoides extracts and assay
Eucommia ulmoides 500g, add the extraction of the alcohol refluxs of 5000ml 85% twice, 2 hours every time, merge extract solution filtering
After be concentrated into the greatest extent, obtain alcohol extracting concentrate.Make D101 macroporous absorbent resins on the concentrate, with 20-80% ethanol elutions, collect capital
Buddhist nun is flat, both geniposides high eluent of content, concentrates, dries, obtain extract.
After testing, in the extract, the amount of Geniposide and geniposide is respectively 16.2%, 7.8%.
Bark of eucommia example 4：Geniposide and geniposide compound are prepared from the bark of eucommia and it is characterized
31.5 kilograms of Eucommia ulmoides (being purchased from District, Xinyang Area, Henan Province medicinal material company) are cut into small pieces, add 315 liter of 95% ethanol leaching
Bubble overnight, refluxing extraction 2 hours, pours out extract solution, and the dregs of a decoction add 315 liter of 95% alcohol reflux and extracted 2 hours, and extract solution closes
Filtered after and, subsequent filtrate recovery ethanol, successively with petroleum ether, chloroform, ethyl acetate and extracting n-butyl alcohol, after solvent is separately recovered
Obtain solid content.As a result：Oil ether moiety solid content 153g, chloroform portion solid content 384g, ethyl acetate portion solid content 126g,
N-butanol fraction solid content 520g.
Bark of eucommia ethyl acetate extraction part, by silica gel column chromatography, take chloroform:Methanol solvate system gradient elution, 19
~27 cuts recycle silica gel column chromatography, by petroleum ether-ethyl acetate solvent system gradient elution, obtain powdered substance,
It is identified as Geniposide.
After bark of eucommia n-butanol fraction 500g crosses D101 macroporous absorbent resins, 30% part 130g carries out silica gel column chromatography point
From EtOAc:CH3OH solvent system gradient elutions, 18~20 flow points are with CHCl3:CH3OH:H2O systems carry out silica gel column chromatography,
There is white powder precipitation in the flow point of gained 8~14, labeled as EUB30-1, after being compared with literature value, it is capital Buddhist nun to determine EUB30-1
Flat glycosides.
Geniposide, white powder.1H-NMR (CD3OD, 500MHz):δ 4.18 (1H, d, J=8.0Hz, H-1), 7.53
(1H,s,H-3),3.14(1H,m,H-5),2.83(1H,m,H-6),2.03(1H,m,H-6),5.83(1H,s,H-7),2.47
(1H, t, J=8.5Hz, H-9), 4.25 (2H, dd, J=14.5Hz, H-10), 3.71 (3H, s ,-OCH3).
Geniposide, white, needle-shaped crystals (methanol), mp are 159~160 DEG C, the aobvious positive of Molish reactions, after sour water solution
Sugar moieties are examined to know through thin-layer chromatography and prove only to contain D-Glucose.1H-NMR(CD3OD):7.51(1H,s,H-3),5.79(1H,
Br.s, H-7), 5.16 (1H, d, J=7.8Hz, H-1), 4.70 (1H, d, J=8.0Hz, H-1 '), 4.19 (2H, q, H-10),
3.70 (3H, s, H-12), 2.70 (2H, t, J=16.0Hz, H-6), 2.10 (1H, q, H-5).13C-NMR(CD3OD):98.2
(C-1),153.4(C-3),112.5(C-4),39.7(C-5),36.6(C-6),128.3(C-7),144.8(C-8),47.0(C-
9),61.4(C-10),169.5(C-11),51.7(C-12),100.3(C-1′),74.8(C-2′),78.4(C-3′),71.5
(C-4′),77.8(C-5′),62.6(C-6′).Above physicochemical data and spectral data are consistent with document, and authenticating compound is capital
The flat glycosides of Buddhist nun.
C, teasel root bark of eucommia compound combined extracts (being also referred to as compound eucommia bark pharmaceutical composition herein) preparation example：
Combine example 1：The preparation and detection of compound eucommia bark pharmaceutical composition
The 500g barks of eucommia and the mixing of 500g teasel roots, add 10 times of 60% ethanol of amount extractions twice, each 2h, merge extract solution and return
Receive ethanol and be concentrated into and most be dried in vacuo to obtain combined extracts.After testing, in the extract, comprising 5.7% akebiasaponin D,
1.2% Pinoresinol diglucoside.
Combine example 2：The preparation and detection of compound eucommia bark pharmaceutical composition
The 50g barks of eucommia and the mixing of 500g teasel roots, add 10 times of amount water extractions twice, each 2h, merge extract solution and be concentrated into the greatest extent
It is dried in vacuo to obtain combined extracts.After testing, in the extract, 3.9% akebiasaponin D, 0.9% grape of rosin spirit two are included
Glucosides.
Combine example 3：The preparation and detection of compound eucommia bark pharmaceutical composition
The 500g barks of eucommia and the mixing of 50g teasel roots, add 10 times of 85% ethanol of amount extractions twice, each 2h, it is dense to merge extract solution
It is reduced to and most is dried in vacuo to obtain combined extracts.After testing, in the extract, 4.6% akebiasaponin D, 1.6% rosin spirit are included
Diglucoside.
Combine example 4：The preparation and detection of compound eucommia bark pharmaceutical composition
The 500g barks of eucommia and the mixing of 500g teasel roots, add 10 times of 70% ethanol of amount extractions twice, each 2h, merge extract solution and return
Ethanol is received to without alcohol taste.Solution adds 4% sodium hydroxide and adjusts pH value to 10-11,60 DEG C of lasting 4h is heated to, with 10% hydrochloric acid
Solution adjusts pH value to neutrality.It is concentrated and dried to obtain combined extracts.
Combine example 5：The preparation and detection of compound eucommia bark pharmaceutical composition
The 500g barks of eucommia and the mixing of 500g teasel roots, add 10 times of 70% ethanol of amount extractions twice, each 2h, merge extract solution and return
Ethanol is received to without alcohol taste.Solution adds 4% sodium hydroxide and adjusts pH value to 10-11,60 DEG C of lasting 4h is heated to, with 10% hydrochloric acid
Solution adjusts pH value to neutrality.D101 macroporous absorbent resins on solution, discard aqueous effluent and water elution, 70% ethanol elution
Liquid is concentrated and dried to obtain combined extracts.
Test of pesticide effectiveness part：
Test example 1：Cell proliferation test
1st, cell culture and drug-treated
MC3T3-E1 cells are used with the α-MEM cellar cultures of nutrient solution containing nucleosides containing 10%FBS when being merged to 80%
0.25% pancreatin is digested, and 96 orifice plates are inoculated in 8000 cells/wells.37 DEG C are placed in, 5%CO2After 24h being cultivated in incubator,
Cell attachment is good, sprawls growth.Nutrient solution is now sucked, is washed 1 time with PBS liquid 1mL/ holes, adds the α-MEM containing 1%FBS
Nutrient solution containing nucleosides 1mL, preculture 24h, synchronizing.Renewal experiment nutrient solution, and various concentrations medicine is added simultaneously.Together
When every piece of 96 orifice plates all set blank control group (0.1%DMSO), estradiol (E2) group (10-8M), each concentration group of medicine, culture
24h。
2nd, cell proliferation rate detects
The propagation of cell needs substantial amounts of energy, for synthesizing various macromolecular substances and completing fission process.Therefore, carefully
The horizontal situation about can be bred with indirect reaction cell of born of the same parents' energetic supersession.Succinate dehydrogenase in living cells mitochondria can be catalyzed
MTT forms blue formazans, and its forming amount is proportionate with viable count and functional status.Formazan dissolves in DMSO, in purple
Color, its colour developing degree can reflect survival and the propagation of cell.This experiment determines the shadow of medicine cell proliferation using this method
Ring.Concrete operation step is as follows：
1. 0.25% pancreatin (containing 0.02%EDTA) vitellophags, 1000rpm centrifugation 5min, supernatant discarding, use cell
Nutrient solution mixes and cell suspension is made.
2. cell counts：The cell suspension for taking 10 μ L to mix, it is added dropwise in being stamped on the cell counting count board of cover glass, aobvious
Counted under micro mirror.
3. cell is inoculated in 96 orifice plates by, per hole 0.2mL nutrient solutions.37 DEG C are placed in, 5%CO2Trained in culture incubator
Support.
4. after cultures 24h, add the μ L of MTT solution (5mg/mL is dissolved with PBS, pH=7.4) 20 per hole.It is small to continue incubation 4
When, culture is terminated, careful inhale abandons culture supernatant in hole.Add 100 μ L DMSO per hole, vibrate 10 minutes, make crystal fully molten
Solution, solution is aubergine.
5. selects 570nm wavelength, in each hole absorbance value of multi-functional read plate aircraft measurements (being represented with A), result is recorded,
Using blank group as standard, each group cell is calculated with respect to proliferation rate (relative proliferative effect, RPE), it is counted
Calculation method is：
RPE=(ASample/AControl）× 100%
3rd, result of the medicine to MC3T3-E1 cell proliferative effects
Radix Dipsaci extract (the μ g/ml of teasel root example 1,100,50,5), eucommia ulmoides extracts (the μ g/ml of bark of eucommia example 1,100,50,5),
Compound eucommia bark extract (combination example 1,100,50,5 μ g/ml), can promote MC3T3-E1 Gegenbaur's cells to increase concentration dependent
(table 1) is grown, compared with blank control group, there is significant difference (P<0.05 or P<0.01).Estradiol is used in experiment simultaneously
(E2) as control, and compound administration osteoblastic proliferation effect is administered better than single medicine.
Table 1：Influence of the medicine to MC3T3-E1 osteoblastic proliferations
*P<0.05, * * P<0.01, compared with the control (n=6)
The extract that # is teasel root and each 500 grams of medicinal material extracts of the bark of eucommia obtain；## is what 1000 grams of medicinal material extracts of teasel root obtained
Extract；### is what 1000 grams of medicinal material extracts of the bark of eucommia obtained；@represents that various extracts are entered with the considerable amount of reagent amount of gross weight
Row experiment.
As a result the percentage bred with cell represents.Individually use DMSO (10-8MoL/L) be incubated be used as 100%, carry reagent with
Control there were significant differences (* p<0.05, * * p<0.01, respective n=6).
In other parallel test, the present inventor is tested respectively with combination example 4 and 5.As a result show, use with
With upper table 1 Suo Shi combine the same dose of example 1 under, combination example 4 and 5 at each dose than combine example 1 RPE results it is high by 7~
16%.It can be seen that the compound for being better than unused alkali process in preparation process with alkali-treated compound eucommia bark pharmaceutical composition effect is shut out
Secondary pharmaceutical composition.
Test example 2：Medicine ERs activation experiment
At 37 DEG C, 5%CO2Under conditions of, used in cell culture incubator containing 10% calf serum without phenol red high sugar
Cell, is laid in 96 orifice plates by DMEM nutrient solution culture Hela cells to during cell density 90% or so by 60% density, per hole
It is middle to add containing 10% serum without phenol red DMEM nutrient solutions 150ul, overnight incubation.By 96 orifice plates per hole 100ul serum-frees DMEM
Culture medium, 0.4 μ g plasmids (ptk-ERE-luc 2 μ g, tk-Renila 1 μ g, ER α or ER β 1 μ g) are transfected.Transfection is 6 small
Shi Hou, 150ul serum-frees are added per hole without phenol red DMEM nutrient solutions.Every group of three holes are chosen, add 10- 8M estradiol E2, and
The tested material 15ul/ holes (the high, medium and low three concentration groups of sample) of various concentrations, 37 DEG C, 5%CO2Under the conditions of to continue culture 24 small
When.80 μ l cell pyrolysis liquids are added after 24 hours per hole, and frozen-thawed cell is once so that it is fully cracked.The cell in every hole is split
Solution liquid determines its activity to Fluc and Renila luciferases respectively.Per Kong Junyong Flucs/
Renila luciferins enzyme values using in each group as a result, do not add the hole of Estrogenization to be used as control, calculating plus estrogen respectively
Or measured object group is averaged relative to the ratio of control group, every group of three holes.As a result it is as shown in table 2：
The activation of the bark of eucommia Radix Dipsaci extract of table 2 and compound eucommia bark side to ERs
*p<0.05, * * p<0.01
In table, " eucommia ulmoides extracts " are the extracts of bark of eucommia example 1, and " Radix Dipsaci extract " is the extract of teasel root example 1, and " compound is shut out
Zhong Fang " is the extract for combining example 1.
As a result show that eucommia ulmoides extracts and compound eucommia bark extract have ERs activation, and compound eucommia bark
Extract ERs activation effect is significantly better than single eucommia ulmoides extracts.As a result prompt more significantly, with the bark of eucommia
Extract increases compared to compound eucommia bark prescription compositions ER β/ER α ratios, illustrates selection of the pharmaceutical composition of the present invention to ER β
Property activation enhancing, this just makes pharmaceutical composition of the present invention while estrogenic activity is played, and reduces promotion mammary gland
The risk of cancer cell multiplication, is suitable for long-term use.In the experiment of the combination example 2 and 3 of use respectively parallel in addition, as a result show
Go out and combine the essentially identical result of example with using.
Test example 3：Medicine is prevented and treated to whole animal osteoporosis and tested
Experimental animal：6 monthly ages of health are selected through producing female SPF Sprague-Dawley rats (SD), average weight
270 scholar 50g.It is grouped as follows：
Sham groups：Sham-operation group；
OVX groups：Ovariectomized group；
Eucommia ulmoides extracts group：Removal ovary+eucommia ulmoides extracts；
Radix Dipsaci extract group：Removal ovary+Radix Dipsaci extract；
Compound eucommia bark group：Removal ovary+compound eucommia bark pharmaceutical composition；
The SD rats at 6 monthly ages used by experiment, proceed by vaginal smear examination within 7 days after ovarian resection.Go
Gesture operation consent vaginal smear shows that the oestrous cycle is present, postoperative only it is observed that the leucocyte of metaoestrus and anoestrum, is moved
Feelings disappearance of periodicity, indicate OVX successful surgeries.Ovarian ablation starts on the 3rd week, is administered continuously 6 weeks.
Influence of the Chinese medicine composition of the present invention to bone density
Dissect and separate right side shin bone, reject accompanying muscle and tendon forceps rapidly, soft tissue is rejected clean but tried one's best not
Destroy periosteum.It is then placed in 70% alcoholic solution and fixes 1 week, is surveyed for peripheral bone quantitative computer tomography (pQCT)
It is fixed.First to shin bone sample longitudinal scanning, after showing the form of proximal tibia, using osteoepiphyseal line as basic point downward 3.0mm and 12.0mm
Place makees tomography measure, and based on cancellous bone, the latter's compact bone is more for the former, and subject compound can be reflected to bone tissue difference portion
The influence of bit architecture.
Bone density result is shown at detection position astragalus epiphyseal line 3.0mm, trabecular bone density, total bone density after ovariectomized rats
Reduce, but cortical bone density changes without obvious.After giving traditional Chinese medicine composition for treating of the present invention, trabecular bone density and total bone density are all
Increased, and compound eucommia bark pharmaceutical composition group increase degree is substantially better than independent teasel root group, better than independent bark of eucommia group.
The influence of the bark of eucommia ball of test example 4 and its composition medicine to senile osteoporosis model mice osteoporosis
1.1 experimental method
1.1.1 experimental animal is administered with packet
Cleaning grade 6 monthly age quick aging osteoporosis model mouse SAMP650, normal homologous reference mouse SAMR110
Only, male, SAMP6 mouse are randomly divided into SAMP6 model groups by body weight, bark of eucommia ball 6g groups, bark of eucommia ball 3g groups, bark of eucommia 3g groups, continued
Disconnected 3g groups, SAMR1 control groups, SAMP6 model groups gavage distilled water respectively, and each group dosage is shown in Table 3, gastric infusion 12 weeks.Its
In, for bark of eucommia ball group using the composition for combining example 1, bark of eucommia group uses the extract of bark of eucommia example 1, and teasel root group uses teasel root example 1
Extract.
The bark of eucommia ball of table 3 and composition simple each group mouse dosage
| Group | Crude drug dosage (g/kg) |
| SAMR1 control groups | - |
| SAMP6 model groups | - |
| Bark of eucommia ball 6g groups | 6 |
| Bark of eucommia ball 3g groups | 3 |
| Bark of eucommia 3g groups | 3 |
| Teasel root 3g groups | 3 |
1.1.2 key instrument is tested
Bone densitometry is detected using the Micro-CT (vivaCT 40) of Scanco Medical AG companies of Switzerland.
2.1 experimental result
Influence (mean ± SD) of the bark of eucommia ball of table 4 to SAMP6 mouse femurs metaphysis bone density bone and volume fraction
| Group | n | BMD(mg/ccm) | TMD(mg/ccm) | BV/TV (%) |
| SAMR1 control groups | 10 | 778.36±14.66 | 463.27±19.28 | 61.16±2.41 |
| SAMP6 model groups | 10 | 740.79±17.85 | 395.75±34.85 | 55.66±3.79 |
| Bark of eucommia ball 6g groups (HW) | 10 | 764.17±16.98 | 459.87±29.56 | 60.94±3.85 |
| Bark of eucommia ball 3g groups (MW) | 9 | 748.77±13.45 | 428.88±26.64 | 59.16±3.88 |
| Bark of eucommia 3g groups (DZ) | 10 | 749.19±8.44 | 396.95±31.98 | 56.40±3.02 |
| Teasel root group 3g groups (XD) | 10 | 740.70±15.13 | 396.48±22.96 | 55.28±2.14 |
Test example 5SAMP6 mouse Morris water maze laboratory results
2.1 experimental method
2.1.1 experimental animal is administered with packet
Same 1.1.1
2.1.2 water maze laboratory hides platform acquisition experimental method
Platform is placed in any quadrant center and position keeps constant, training 4 times, each 60s daily, is carried out 5 days altogether.Will
For animal towards being put into water on pool wall, it be Success in Experiment that animal, which finds and climbs up platform and be detained full 2s in platform, records and is taken
Between i.e. escape latency (escapelateney).If animal does not find platform in 60s, directed it to by experimenter flat
Platform, escape latency are designated as 60s.Allow mouse to stop 20s on platform no matter whether animal successfully searches out platform, mouse is put
In the withdrawal of currency from circulation after rest 30s, trained next time.After the completion of 4 training, animal is cleaned dried rapidly, be placed in by heater
Drying.Wherein, bark of eucommia ball group is using the composition of combination example 1, and using the extract of bark of eucommia example 1, teasel root group uses continuous bark of eucommia group
The extract of disconnected example 1.As a result see the table below.
The influence (mean ± SD) of the bark of eucommia ball of table 5 and composition simple to SAMP6 mouse escape latencies (s)
In table, # represents P<0.05, ## represents P<0.01, compared with SAMP6 model groups.
As a result show：There is bone aging simultaneously in SAMP6, also show the impaired brain aging phenomenon of cognition and memory.Bark of eucommia ball
The hidden platform of SAMP6 mouse can significantly be shortened and obtain experiment escape latency, prompt bark of eucommia ball to significantly improve experimental animal
Ability of learning and memory, for the especially aging women of the elderly concurrent brain aging of osteoporosis caused by estrogen is certain
Effect is significantly improved, it is corresponding medicine to be expected to exploitation.
Applicant is in other experiment, using the compound eucommia bark pharmaceutical composition of combination example 4 as experiment reagent, with
The capsule that CN1448176A embodiments 1 obtain is as control reagent, to be diagnosed as osteoporosis outpatients as clinic
The object of observation, accept patient for medical treatment and be divided into 2 groups for totally 86.Treatment method：The patient of osteoporosis is diagnosed as, is tried with above-mentioned experiment
Based on medicine and control reagent, coordinate corresponding drug therapy with reference to clinical symptoms.Drug usage：Compare reagent capsule daily 3
It is secondary, 4 tablets each time；The bark of eucommia and teasel root with compareing suitable dosage in reagent are taken in experiment reagent daily, point 3 clothes.As a result：Experiment
Reagent group total effective rate 86.1%, experiment reagent group total effective rate 85.6%, the two is essentially identical.
Claims (7)
1. composition is preparing the purposes in being used to treat and/or prevent the medicine of post menopausal cognitive defect disease, the combination
Thing is prepared by the extract of Chinese medicine teasel root and the bark of eucommia, and both the teasel root and the bark of eucommia weight ratio are 0.1~10：1,
The extract is that both teasel root and the bark of eucommia one reinstates water or hydrous ethanol extraction, then optionally uses alkali process and/or macropore tree
It is concentrated to give after fat processing.
2. the purposes of claim 1, both the teasel root and the bark of eucommia weight ratio are (0.2~5)：1.
3. the purposes of claim 1, the hydrous ethanol is 30%~95% ethanol.
4. the purposes of claim 1, the hydrous ethanol is 50%~90% ethanol.
5. the purposes of claim 1, following material is selected from comprising at least one in the composition：Wei rock celestial beings saponin A, 3-O-
A-L- arabopyranoses-oleanolic acid -28-O- β-D- glucopyranoses-(1 → 6)-β-D- glucopyranosides, vomiting nut
Glycosides, split loganin glycosides, triplostoside A, Geniposide, geniposide, Geniposidic acid, betulic acid, aucubin,
Pinoresinol diglucoside, syringaresinol diglucoside, rosin spirit list glucoside, syringaresinol list glucoside, the Chinese are yellow
A kind of reed mentioned in ancient books element, Chiba element A, baicalein, dihydrochalcone 3-O- β-D-Glucose glycosides, α-oxygen-β-D- glucopyanosyls base -4,2 ', 4 ' -
Trihydroxy dihydrochalcone, chlorogenic acid, akebiasaponin D.
6. the purposes of claim 1, following material is selected from comprising at least one in the composition：Wei rock celestial beings saponin A, 3-O-
A-L- arabopyranoses-oleanolic acid -28-O- β-D- glucopyranoses-(1 → 6)-β-D- glucopyranosides, vomiting nut
Glycosides (Loganin), split loganin glycosides, triplostoside A, Geniposide, geniposide, Geniposidic acid, betulic acid, peach
Leaf coral glycosides, Pinoresinol diglucoside, syringaresinol diglucoside, rosin spirit list glucoside, syringaresinol list grape
Glucosides, wogonin, Chiba element A, baicalein, dihydrochalcone 3-O- β-D-Glucose glycosides, α-oxygen-β-D- glucopyanosyls
Base -4,2 ', 4 '-trihydroxy dihydrochalcone, chlorogenic acid, akebiasaponin D, and when there is their more than two kinds, they
Weight rate arbitrarily between the two is 0.0001~10000：1.
7. the purposes of claim 1, the composition is in tablet, capsule, soft capsule, pill, topical agent or injection
The form of preparation.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201410397179.9A CN104173418B (en) | 2011-07-28 | 2012-07-19 | The composition and purposes of the bark of eucommia and teasel root |
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201110213458.1 | 2011-07-28 | ||
| CN201110213458 | 2011-07-28 | ||
| CN2011102134581 | 2011-07-28 | ||
| CN201210250590.4A CN102824400B (en) | 2011-07-28 | 2012-07-19 | Composition containing eucommia ulmoides and teasel roots and application of composition for treating osteoporosis |
| CN201410397179.9A CN104173418B (en) | 2011-07-28 | 2012-07-19 | The composition and purposes of the bark of eucommia and teasel root |
Related Parent Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201210250590.4A Division CN102824400B (en) | 2011-07-28 | 2012-07-19 | Composition containing eucommia ulmoides and teasel roots and application of composition for treating osteoporosis |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN104173418A CN104173418A (en) | 2014-12-03 |
| CN104173418B true CN104173418B (en) | 2018-03-20 |
Family
ID=47327846
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201210250590.4A Active CN102824400B (en) | 2011-07-28 | 2012-07-19 | Composition containing eucommia ulmoides and teasel roots and application of composition for treating osteoporosis |
| CN201410397179.9A Active CN104173418B (en) | 2011-07-28 | 2012-07-19 | The composition and purposes of the bark of eucommia and teasel root |
Family Applications Before (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201210250590.4A Active CN102824400B (en) | 2011-07-28 | 2012-07-19 | Composition containing eucommia ulmoides and teasel roots and application of composition for treating osteoporosis |
Country Status (1)
| Country | Link |
|---|---|
| CN (2) | CN102824400B (en) |
Families Citing this family (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102920769B (en) * | 2012-11-13 | 2014-07-09 | 杨中林 | Application of eucommia ulmoides bolus in preparation of medicines treating osteoporosis |
| CN103301246A (en) * | 2013-06-20 | 2013-09-18 | 史凤娥 | Wind and cold-dampness lumbago treatment medicine and preparation method thereof |
| EP3251683A4 (en) * | 2015-01-30 | 2018-09-26 | Sichuan Jiuzhang Biological Science And Technology Co., Ltd | Eucommia leaf extract, and preparation method and use thereof |
| KR101698051B1 (en) * | 2016-01-13 | 2017-01-20 | 아주대학교산학협력단 | Composition for preventing, improving or treating female menopause symptoms comprising Loganin or its derivatives |
| CN106380497A (en) * | 2016-08-29 | 2017-02-08 | 马健 | Method for extracting pinoresinol diglucoside of eucommia |
| CN110632236B (en) * | 2019-09-16 | 2021-07-02 | 广东省测试分析研究所（中国广州分析测试中心） | Method for rapidly identifying three active ingredients of folium cortex eucommiae and cortex eucommiae by thin-layer chromatography |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1682788A (en) * | 2004-04-12 | 2005-10-19 | 赵晓昂 | Shutongfang for killing pain and its preparation and use |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102507825B (en) * | 2011-11-01 | 2013-12-25 | 广东医学院 | Detecting method for effective components of traditional Chinese medicine Hugu capsules for preventing and treating osteoporosis |
-
2012
- 2012-07-19 CN CN201210250590.4A patent/CN102824400B/en active Active
- 2012-07-19 CN CN201410397179.9A patent/CN104173418B/en active Active
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1682788A (en) * | 2004-04-12 | 2005-10-19 | 赵晓昂 | Shutongfang for killing pain and its preparation and use |
Non-Patent Citations (1)
| Title |
|---|
| 四子散热熨配合辨证施护治疗膝关节骨性关节炎76例;邱瑞娟等;《新中医》;20060630;第38卷(第6期);第78页 * |
Also Published As
| Publication number | Publication date |
|---|---|
| CN102824400A (en) | 2012-12-19 |
| CN102824400B (en) | 2015-01-07 |
| CN104173418A (en) | 2014-12-03 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN104173418B (en) | The composition and purposes of the bark of eucommia and teasel root | |
| CN102526165B (en) | A kind of Radix Rhodiolae effective site, its preparation method, its pharmaceutical composition and purposes | |
| CN102389440B (en) | Application of iridoid in preparation of anti-osteoporosis medicines | |
| CN101242850A (en) | Composition, function and use of xanthoceras sorbifolia extract and compound isolated from same, method for preparing same | |
| CN102178741B (en) | Guava leaf extract with function of reducing blood sugar as well as preparation method and application thereof | |
| CN101647850B (en) | New application of chemical component of eucommia bark used as plant estrogen | |
| CN101759544B (en) | Novel chalcone compound and preparation method and application thereof | |
| CN101085091A (en) | Traditional Chinese medicine extraction for preventing and curing osteoporosis and its preparation method | |
| CN101972294A (en) | New usage of eucommia ulmoides chemical composition as vessel protective agent | |
| EP3339285B1 (en) | A compound isolated from isodon forrestii var. forrestii and preparation method and applications thereof | |
| CN102796112B (en) | Prenylflavonoid compound and application thereof in preparation of pancrelipase inhibitor | |
| CN102007110B (en) | For preventing, treat the Flavonol compound of bone health relevant disease, the bioactive extracts/fraction of elm and compound thereof | |
| CN108014118A (en) | A kind of purposes of notoginsenoside Ft1 | |
| CN106619652A (en) | Preparation method of spermacoce latifolia triterpenoids and application of spermacoce latifolia triterpenoids in preparation of glycosidase inhibitor drug | |
| CN100594913C (en) | Medicine combination for curing diabetes and complication thereof and the preparing method and purpose | |
| CN103083388B (en) | Preparation method of fructus gleditsiae total saponins | |
| CN100479811C (en) | Medicinal composition containing backuchiol for treating female breast cancer | |
| CN108059592A (en) | Deoxygenate aromatic A of rhizoma nardostachyos and preparation method and application | |
| CN101152320A (en) | Traditional Chinese medicine preparation for treating gynecology pelvic inflammatory disease | |
| CN103118688A (en) | New use of chemical ingredients in cynomorium as phytoestrogen | |
| CN107496725A (en) | Functional food composition and purposes of the thing as active ingredient are taken using Hubei Chinese flowering crabapple and bamboo | |
| CN102861044B (en) | Novel application of himalayan teasel root chemical compositions | |
| CN104189346A (en) | New pharmaceutical composition capable of promoting gastrointestinal motility and preparation method thereof | |
| CN110063960A (en) | 3- hydrogenates the pharmaceutical applications of loose Siberian cocklebur acid B cyanogen methyl esters | |
| CN101497568B (en) | Use of Sichuang-Tibet amethystoidin A in preventing and treating acute lymphocyte leukaemia and cervical cancer |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant |