CN105646406A - Novel cyclofarnesane-type sesquiterpenoid as well as preparation method and pharmaceutical application thereof - Google Patents

Novel cyclofarnesane-type sesquiterpenoid as well as preparation method and pharmaceutical application thereof Download PDF

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CN105646406A
CN105646406A CN201610113350.8A CN201610113350A CN105646406A CN 105646406 A CN105646406 A CN 105646406A CN 201610113350 A CN201610113350 A CN 201610113350A CN 105646406 A CN105646406 A CN 105646406A
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compound
preparation
extract
ethanol elution
alcohol
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叶胜
姚思梦
李新
钱元
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Anhui University of Science and Technology
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Anhui University of Science and Technology
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
    • C07D307/02—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings
    • C07D307/34—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
    • C07D307/56—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D307/58—One oxygen atom, e.g. butenolide

Abstract

The invention discloses a novel cyclofarnesane-type sesquiterpenoid as well as a preparation method and a pharmaceutical application thereof. The sesquiterpenoid is reported for the first time, is a cyclofarnesane-type sesquiterpenoid adopting a novel structure and can be obtained from dried stems of Dendrobium nobile through extraction, separation and purification. In-vitro tests prove that toxicity of Abeta1-40 damages nerve cells and causes apoptosis of a large amount of PC12 and reduction of cell viability, the apoptosis condition is improved after being intervened by the sesquiterpenoid, and the sesquiterpenoid can be developed into a medicine for neuroprotection.

Description

A kind of new ring Acacia farnesiana Willd. alkane type sesquiterpene compound and preparation method thereof and medical usage
Technical field
The invention belongs to technical field of pharmaceuticals, be specifically related to separate a kind of ring Acacia farnesiana Willd. alkane type sesquiterpene compound with neuroprotective of obtaining and preparation method thereof from the dry stem of Dendrobium nobile.
Background technology
Dendrobium nobile (DendrobiumnobileLindl.) is China's tradition rare Chinese medicine, for the orchid family Dendrobium Sw, has another name called Dendrobium nobile Lindl stone, flat Dendrobium nobile Lindl, flat Dendrobium denneanum Kerr. etc., and its stem is one of source of Chinese medicine Herba Dendrobii, is recorded by going through an edition Chinese Pharmacopoeia. Herba Dendrobii is just on the books in Shennong's Herbal, and Compendium of Material Medica claims it to have the effect of " reinforcing YIN-essence benefit the intestines and stomach smart, thick, mend in spore is not enough, make light of one's life by commiting suicide and prolong life ". The history tree such as amplification on Canon of Materia Medica, supplementary Amplifications of the Compendium of Materia Medica and " Bencao Congxin " is all standby adds high praise, have the title of " a thousand pieces of gold grass ". Dendrobium nobile, cold nature, sweet in the mouth, for consumption of body fluid caused by febrile disease, xerostomia excessive thirst, after being ill deficiency-heat, poor vision, atrophic gastritis, superficial gastritis, chronic colitis etc., is the important compatibility of the preparations such as SHIHUYEGUANG WAN, shihu mingmu pills, Herba Dendrobii extractum solution, Herba Dendrobii QINGWEI SAN. Dendrobium nobile is classified as the primary source of medicinal dendrobium for 2010 at Chinese Pharmacopoeia in version.
Over nearly 20 years, the chemical composition of Dendrobium Sw has been explored and has been studied by Chinese scholars, it has been found that the chemical composition type contained by these plants is various. The chemical composition of Dendrobium nobile mainly has alkaloids, polysaccharide, flavonoid, phenols, sesquiterpenoids, Coumarins and steroidal glycoside compounds. Alkaloids composition is the compound separating and carrying out Structural Identification the earliest from Dendrobium Sw, is also the characteristic chemical constituent of orchid. In the last few years, the alkaloids composition in Dendrobium nobile has been carried out substantial amounts of research by Chinese scholars, and the alkaloid identified so far is mainly sesquiterpenoids alkaloid, and wherein dendrobine is its characteristic chemical constituent.
The pharmacological action of Dendrobium nobile is mainly manifested in the effect to cardiovascular system, neural effect, antitumor and antimutagenesis, antioxidation and anti-aging effects, anti-cataract effect and immunosuppressant, calcium channel is suppressed, antiinflammatory action and to gastrointestinal effect.
Summary of the invention
It is an object of the invention to provide a kind of a kind of ring Acacia farnesiana Willd. alkane type sesquiterpene compound with neuroprotective separating from the dry stem of Dendrobium nobile and obtaining and preparation method thereof.
The above-mentioned purpose of the present invention is achieved by the techniques below scheme:
There is the compound (I) of following structural formula,
The preparation method of described compound (I), comprise following operating procedure: the dry stem of Dendrobium nobile is pulverized by (a), extract with 80��90% alcohol heat reflux, united extraction liquid, it is concentrated into without alcohol taste, successively with petroleum ether, ethyl acetate and water saturated n-butanol extraction, respectively obtain petroleum ether extract, acetic acid ethyl ester extract and n-butyl alcohol extract; B acetic acid ethyl ester extract macroporous resin remove impurity in () step (a), first with 6 column volumes of 10% ethanol elution, then with 10 column volumes of 75% ethanol elution, collects 75% ethanol elution, concentrating under reduced pressure obtains 75% ethanol elution thing extractum; In (c) step (b) 75% ethanol elution extractum with purification on normal-phase silica gel separate, successively with volume ratio be 85:1,55:1,25:1,10:1 and 1:1 methylene chloride-methanol gradient elution obtain 5 components; D in () step (c), component 4 separates further by purification on normal-phase silica gel, successively with volume ratio be 15:1,10:1 and 5:1 methylene chloride-methanol gradient elution obtain 3 components; E reverse phase silica gel that in () step (d), component 2 is bonded by octadecylsilane separates, with the methanol aqueous solution isocratic elution that concentration expressed in percentage by volume is 70%, collecting 8��10 column volume eluents, eluent concentrating under reduced pressure obtains pure compound (I).
Further, described macroporous resin is AB-8 type macroporous adsorbent resin.
Further, described alcohol heat reflux extracts the concentration of alcohol adopted is 85%.
A kind of pharmaceutical composition, wherein contains the described compound (I) of therapeutically effective amount and pharmaceutically acceptable carrier.
The application in the medicine preparing neuroprotective of the described compound (I).
The application in the medicine preparing neuroprotective of the described pharmaceutical composition.
When the compounds of this invention is used as medicine, it is possible to directly use, or use with the form of pharmaceutical composition.
This pharmaceutical composition contains the compounds of this invention (I) of therapeutically effective amount, and all the other are acceptable on materia medica, humans and animals is nontoxic and pharmaceutically suitable carrier of inertia and/or excipient.
Described pharmaceutically suitable carrier or excipient are that one or more are selected from solid, semisolid and liquid diluent, filler and pharmaceutical preparation adjuvant. The pharmaceutical composition of the present invention is used with the form of per weight dose. Medicine of the present invention can be applied to, by oral or injection form, the patient needing treatment. During for being administered orally, tablet, slow releasing tablet, controlled release tablet, capsule, drop pill, micropill, suspensoid, Emulsion, powder or granule, oral liquid etc. can be made into; During for injecting, can be made into the aqueous of sterilizing or oily solution, aseptic powder injection, liposome or Emulsion etc.
Accompanying drawing explanation
Fig. 1 is compound (I) structural formula;
Fig. 2 is that the theoretical ECD value of compound (I) compares with experiment ECD value.
Detailed description of the invention
Further illustrate the essentiality content of the present invention below in conjunction with embodiment, but do not limit scope with this. Although the present invention being explained in detail with reference to preferred embodiment, it will be understood by those within the art that, it is possible to technical scheme is modified or equivalent replacement, without deviating from the spirit and scope of technical solution of the present invention.
Embodiment 1: compound (I) separates preparation and structural identification
Reagent source: ethanol, petroleum ether, ethyl acetate, n-butyl alcohol, dichloromethane are analytical pure, purchased from Shanghai Ling Feng chemical reagent company limited, methanol, analytical pure, purchased from Jiangsu Han Bang chemical reagent company limited.
Preparation method: the dry stem (8kg) of Dendrobium nobile is pulverized by (a), (25L �� 3 time) are extracted with 85% alcohol heat reflux, united extraction liquid, it is concentrated into without alcohol taste (3L), extract with petroleum ether (3L �� 3 time), ethyl acetate (3L �� 3 time) and water saturated n-butyl alcohol (3L �� 3 time) successively, respectively obtain petroleum ether extract, acetic acid ethyl ester extract (345g) and n-butyl alcohol extract; Acetic acid ethyl ester extract AB-8 type macroporous resin remove impurity in (b) step (a), first with 6 column volumes of 10% ethanol elution, again with 10 column volumes of 75% ethanol elution, collecting 75% ethanol elution, concentrating under reduced pressure obtains 75% ethanol elution thing extractum (133g); C in () step (b), 75% ethanol elution extractum purification on normal-phase silica gel separates, obtain 5 components with the methylene chloride-methanol gradient elution that volume ratio is 85:1 (8 column volumes), 55:1 (8 column volumes), 25:1 (6 column volumes), 10:1 (8 column volumes) and 1:1 (5 column volumes) successively; D in () step (c), component 4 (27g) separates further by purification on normal-phase silica gel, obtain 3 components with the methylene chloride-methanol gradient elution that volume ratio is 15:1 (8 column volumes), 10:1 (10 column volumes) and 5:1 (6 column volumes) successively; E reverse phase silica gel that in () step (d), component 2 (13g) is bonded by octadecylsilane separates, with the methanol aqueous solution isocratic elution that concentration expressed in percentage by volume is 70%, collecting 8-10 column volume eluent, eluent concentrating under reduced pressure obtains pure compound (I) (32mg).
Structural identification: colorless oil; HR-ESIMS shows [M+Na]+For m/z269.1224, can obtain molecular formula in conjunction with nuclear-magnetism feature is C15H18O3, degree of unsaturation is 7. Hydrogen nuclear magnetic resonance modal data ��H(ppm, DMSO-d6, 500MHz): H-2 (2.48, m), H-2 (2.21, m), and H-4 (3.19, m), H-4 (3.05, m), and H-6 (2.48, br, d, J=10.0), and H-7 (6.04, dd, J=16.1,10.0), H-8 (6.37, d, J=16.1), H-10 (5.81, br, s), and H-12 (0.82, s), H-13 (0.94, s), H-14 (4.86, m), and H-14 (4.47, m), H-15 (4.96, s, 2H); Carbon-13 nmr spectra data ��C(ppm, DMSO-d6, 125MHz): 27.9 (C, 1-C), 59.8 (CH2, 2-C), 204.6 (C, 3-C), 51.7 (CH2, 4-C), 145.5 (C, 5-C), 56.4 (CH, 6-C), (138.7 CH, 7-C), 124.2 (CH, 8-C), 161.1 (C, 9-C), (114.5 CH, 10-C), 173.6 (C, 11-C), 21.1 (CH3, 12-C), 30.3 (CH3, 13-C), 111.2 (CH2, 14-C), 70.2 (CH2, 15-C); Carbon atom labelling is referring to Fig. 1. Infrared spectrum shows that this compound contains ��, ��-unsaturated-gamma lactone and carbonyl (1760,1648cm-1)��1H-NMR modal data shows two methyl signals [�� H0.82 (s, Me-12), 0.94 (s, Me-13)], one oxygen-containing methylene signals [�� H4.96 (2H, s, H-15)], an olefinic methylene signals [�� H4.47 (m, H-14) and 4.86 (m, ], and three olefinic methine protons [�� H5.81 (br, s H-14), H-10), 6.04 (dd, J=16.1,10.0Hz, H-7), 6.37 (d, J=16.1Hz, H-8)].13CNMR spectrum shows 15 carbon signals, including two methyl, four methylene [�� C70.2 containing Oxymethylene (C-15), one olefinic methylene �� C111.2 (C-14)], four methine [three olefinics methine �� C114.5 (C-10), 124.2 (C-8) He 138.7 (C-7)], five quaternary carbons [two olefinics quaternary carbon �� C145.5 (C-5) and 161.1 (C-9), two carbonyl carbon �� C173.6 (C-11) and 204.6 (C-3)].H-2 (�� H2.48), H-4 (�� H3.19), H in HMBC spectrum3-12, H3-13 and H2-14 with methine carbon (C-6), H2-2, H-6, H3-12 and H3-13 and C-1, and H2-4, H-6 and H2With the dependency of C-5 ,-14 show that this compound contains a hexamethylene, and it is connected with carbonyl, and gem-dimethyl group is, an and outer methylene of ring. Methine C-6 is connected with trans olefins (J=16.1Hz), and the opposite side (C-8) of trans olefins and ��, ��-unsaturated-gamma lactone ring are connected. H-7 and C-9, H-8 and C-9, C-10 and C-15, H-10 and C-11, and H in HMBC spectrum2-15 and the above-mentioned inference of relevance verification of C-8, C-9, C-10 and C-11. Comprehensive hydrogen spectrum, carbon spectrum, HMBC spectrum and NOESY spectrum, and document is about correlation type nuclear magnetic data, can substantially determine this compound as it is shown in figure 1, spatial configuration is determined by ECD test further, theoretical value and experiment value basically identical (Fig. 2).
Embodiment 2: compound (I) pharmacological action is tested
One, material and instrument
PC12 cell strain, gifts in Anhui Chinese Medicine College experimental center. A ��1-40Albumen is purchased from Sigma company. Compound (I) is self-control, and HPLC normalization purity is more than 98%. (import subpackage is purchased from Beijing match Mo Feishier biochemistry Products Co., Ltd to DMEM/F12 culture medium. NewbomCalfSerum is purchased from BeijingSolarbioScience&TechnologyCo., Ltd. MTT is purchased from Amresco company of the U.S.. Triumphant base AnnexinV-FITC cell apoptosis detection kit is purchased from Nanjing Kai Ji Bioisystech Co., Ltd. Paraformaldehyde is purchased from chemical reagent company limited of Chinese Medicine group. Bcl-2 polyclonal antibody is purchased from Wuhan doctor's moral Bioisystech Co., Ltd. Bax polyclonal antibody is purchased from Beijing Bo Aosen Bioisystech Co., Ltd. Cyt-c polyclonal antibody is purchased from Wuhan doctor's moral Bioisystech Co., Ltd. Goat anti-rabbit igg/FITC is purchased from Beijing Bo Aosen Bioisystech Co., Ltd. Sheep anti-mouse igg/(H+L) is purchased from the green skies biotech firm in Jiangsu. Normal Goat Serum is purchased from Wuhan doctor's moral Bioisystech Co., Ltd. SABC immunohistochemical kit is purchased from Wuhan Boster Biological Technology Co., Ltd.. DAB colour reagent box is purchased from Wuhan doctor's moral Bioisystech Co., Ltd.
Electronic analytical balance (FA2004 type, Shanghai Lei Ci precision scientific instrument company), water-bath (HH SI1-4 type, Beijing medical apparatus and instruments factory), microplate reader (ELx-800 type, U.S. Bio-Tek), flow cytometer (EPICXL-MCL type, BeckmanCouiter company of the U.S.), High speed refrigerated centrifuge (3K30 type, Sigma Co., USA, CO2 gas incubator (CO-150 type, NBS company limited of the U.S.), OLYMPUS fluorescence microscope (BX41 type, band DP70 camera system, Japan's Olympus Products).
Two, test method
1��A��1-40Hatch
A��1-40It is configured to 1000 ��m of ol/L with deionized water and stores liquid subpackage, be positioned over the storage of-20 DEG C of refrigerator, face and hatch 7d with taking-up the last week at 37 DEG C of incubators, so as to assemble aging.
2, the cultivation of cell
PC12 cell strain is cultivated in glass culture bottle with containing 10% hyclone, 100U/ and the DMEM/F12 culture medium of penicillin, 100U/mL streptomycin, CO2The condition of culture of cell culture incubator is 37 DEG C, 5%CO2Concentration, saturated humidity, go down to posterity 1 time (about 2-3d) with the trypsinization of 0.25% after cell length to 80% abundance, inverted microscope observation of cell upgrowth situation, trophophase cell of taking the logarithm during experiment is tested. Seed cells into 96 well culture plate serum-free mediums before carrying out MTT experiment to cultivate;Cell is seeded to before flow cytomery 6 well culture plate serum-free cultures both cultivated; Immunohistochemical experiment is used that 24 well culture plate creep plate methods cultivate cell, and culture medium is serum-free medium.
3, cell administration processes and packet
Cell is divided into five groups, carries out pharmaceutical intervention: 1. Normal group: normal PC12 cell after serum-free medium inoculation 24h; 2. model group: 25 ��m of ol/LA ��1-40; 3. compound (I) low dose group: 25 ��m of ol/LA ��1-40+ 50mg/L compound (I); 4. dosage group in compound (I): 25 ��m of ol/LA ��1-40+ 100mg/L compound (I); 5. compound (I) high dose group: 25 ��m of ol/LA ��1-40+ 200mg/L compound (I). Detection indices is carried out after drug treating 24h.
4, MTT detects each group of cell viability
Take the logarithm the cell of trophophase, with 1 �� 10 after trypsinization5The cell density of individual/mL, every hole 100 �� L is inoculated in 96 orifice plates serum-free culture 24h, then according to above-mentioned group technology carries out pharmaceutical intervention, often group arranges 6 multiple holes, and after 24h, every hole adds the MTT solution 20 �� L of 5mg/mL and continues at CO2Hatching 4h in cell culture incubator, then take out 96 well culture plates, abandoning supernatant, every hole adds the DMSO of 150 �� L, is placed on shaking table vibration 10min, detects the light absorption value in each hole after purple crystal is completely dissolved by microplate reader at 490nm wavelength place. With the hole that only adds culture fluid for zeroing reference, cell viability percentage expression, is 100% depending on the cytoactive of matched group. Result calculates: cell survival rate=(experimental group OD value-blank group OD value)/(matched group OD value-blank group OD value) �� 100%.
5, statistical analysis
Adopting SPSS17.0 to analyze software statistical result is processed, data acquisition one factor analysis of variance, by mean scholar's standard deviationRepresenting, adopting LSD to compare between group, P < 0.05 is for having significant difference, and P < 0.01 is extremely significant difference, and chart is drawn by Excel2003.
Three, result and conclusion
MTT test result shows, compare with normal group cell, model group cytoactive substantially reduces (P<0.01), after compound (I) is intervened, cytoactive increases, wherein the rising of dosage group cytoactive high, middle has statistical significance (P<0.01, P<0.05), low dose group cytoactive changes little (P>0.05). In Table 1 (comparing * P<0.05, * * P<0.01 with model group).
Conclusion, this study demonstrates that A ��1-40Toxicity damage neurocyte, cause a large amount of apoptosis of PC12, cytoactive decline, compound (I) intervene after apoptosis situation improve.
Table 1MTT method compound (I) is to A ��1-40Induction PC12 cytoactive impact (N=6)
Group Processing method Cytoactive (%)
Normal group �C 100��0.0**
Model group 25��mol/L A��1-40 50.08��6.67
Compound (I) low dose group 25��mol/L A��1-40+ 50mg/L compound (I) 58.78��12.64
Dosage group in compound (I) 25��mol/L A��1-40+ 100mg/L compound (I) 63.77��6.81*
Compound (I) high dose group 25��mol/L A��1-40+ 200mg/L compound (I) 83.95��10.58**
Embodiment 3
The preparation of tablet: first prepare compound (I) by embodiment 1 method, and utilize the salt that organic acid such as tartaric acid or citric acid or formic acid or ethanedioic acid etc., mineral acid example hydrochloric acid or sulphuric acid or phosphoric acid makes, excipient, pelletizing press sheet is added with excipient weight than the ratio for 1:9 in it.
Embodiment 4
Prepared by oral liquid: first prepare compound (I) by embodiment 1 method, and utilizing the salt that organic acid such as tartaric acid or citric acid or formic acid or ethanedioic acid etc., mineral acid example hydrochloric acid or sulphuric acid or phosphoric acid makes, oral liquid method for making makes oral liquid routinely.
Embodiment 5
The preparation of capsule or granule: first prepare compound (I) by embodiment 1 method, and utilize the salt that organic acid such as tartaric acid or citric acid or formic acid or ethanedioic acid etc., mineral acid example hydrochloric acid or sulphuric acid or phosphoric acid makes, add excipient with excipient weight than the ratio for 1:9 in it, make capsule or granule.
Embodiment 6
The preparation of injection: first prepare compound (I) by embodiment 1 method, and utilize the salt that organic acid such as tartaric acid or citric acid or formic acid or ethanedioic acid etc., mineral acid example hydrochloric acid or sulphuric acid or phosphoric acid makes, injecting routinely and use water, fine straining, injection is made in embedding sterilizing.
Embodiment 7
The preparation of aseptic powder injection: first prepare compound (I) by embodiment 1 method, and utilize the salt that organic acid such as tartaric acid or citric acid or formic acid or ethanedioic acid etc., mineral acid example hydrochloric acid or sulphuric acid or phosphoric acid makes, it is dissolved in sterile water for injection, stirring makes molten, filter with aseptic suction funnel, aseptic fine straining again, is sub-packed in ampoule, and after frozen drying, aseptic sealing by fusing obtains injectable powder.
The effect of above-described embodiment indicates that the essentiality content of the present invention, but does not limit protection scope of the present invention with this. It will be understood by those within the art that, it is possible to technical scheme is modified or equivalent replacement, without deviating from essence and the protection domain of technical solution of the present invention.

Claims (7)

1. there is the compound (I) of following structural formula,
2. the preparation method of the compound (I) described in claim 1, it is characterized in that comprising following operating procedure: the dry stem of Dendrobium nobile is pulverized by (a), extract with 80��90% alcohol heat reflux, united extraction liquid, it is concentrated into without alcohol taste, successively with petroleum ether, ethyl acetate and water saturated n-butanol extraction, respectively obtain petroleum ether extract, acetic acid ethyl ester extract and n-butyl alcohol extract; B acetic acid ethyl ester extract macroporous resin remove impurity in () step (a), first with 6 column volumes of 10% ethanol elution, then with 10 column volumes of 75% ethanol elution, collects 75% ethanol elution, concentrating under reduced pressure obtains 75% ethanol elution thing extractum; In (c) step (b) 75% ethanol elution extractum with purification on normal-phase silica gel separate, successively with volume ratio be 85:1,55:1,25:1,10:1 and 1:1 methylene chloride-methanol gradient elution obtain 5 components; D in () step (c), component 4 separates further by purification on normal-phase silica gel, successively with volume ratio be 15:1,10:1 and 5:1 methylene chloride-methanol gradient elution obtain 3 components; E reverse phase silica gel that in () step (d), component 2 is bonded by octadecylsilane separates, with the methanol aqueous solution isocratic elution that concentration expressed in percentage by volume is 70%, collecting 8��10 column volume eluents, eluent concentrating under reduced pressure obtains pure compound (I).
3. the preparation method of compound according to claim 2 (I), it is characterised in that: described macroporous resin is AB-8 type macroporous adsorbent resin.
4. the preparation method of compound according to claim 2 (I), it is characterised in that: it is 85% that described alcohol heat reflux extracts the concentration of alcohol adopted.
5. a pharmaceutical composition, it is characterised in that: wherein contain the compound (I) described in the claim 1 of therapeutically effective amount and pharmaceutically acceptable carrier.
6. the application in preparing nerve protection medicine of the compound (I) described in claim 1.
7. the application in preparing nerve protection medicine of the pharmaceutical composition described in claim 5.
CN201610113350.8A 2016-02-29 2016-02-29 Novel cyclofarnesane-type sesquiterpenoid as well as preparation method and pharmaceutical application thereof Pending CN105646406A (en)

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Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN105294665A (en) * 2015-12-01 2016-02-03 吕涛 Novel diterpene compound for neuroprotection
CN105461782A (en) * 2016-01-14 2016-04-06 郑平珍 Novel triterpene compound and preparation and medical application thereof

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* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN105175262A (en) * 2015-08-07 2015-12-23 中国药科大学 Chrysotoxine bibenzyl derivative and preparation method and application thereof
CN105218489A (en) * 2015-10-09 2016-01-06 吴正锋 A kind of assorted terpene compound newly and preparation method thereof and medicinal use
CN105294665A (en) * 2015-12-01 2016-02-03 吕涛 Novel diterpene compound for neuroprotection
CN105330717A (en) * 2015-10-29 2016-02-17 淄博夸克医药技术有限公司 Novel triterpenoid and preparation method and medical application thereof
CN105669611A (en) * 2016-02-20 2016-06-15 杭州富阳伟文环保科技有限公司 Novel ring farnesane type sesquiterpenes compound and preparation method and medical application thereof

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN105175262A (en) * 2015-08-07 2015-12-23 中国药科大学 Chrysotoxine bibenzyl derivative and preparation method and application thereof
CN105218489A (en) * 2015-10-09 2016-01-06 吴正锋 A kind of assorted terpene compound newly and preparation method thereof and medicinal use
CN105330717A (en) * 2015-10-29 2016-02-17 淄博夸克医药技术有限公司 Novel triterpenoid and preparation method and medical application thereof
CN105294665A (en) * 2015-12-01 2016-02-03 吕涛 Novel diterpene compound for neuroprotection
CN105669611A (en) * 2016-02-20 2016-06-15 杭州富阳伟文环保科技有限公司 Novel ring farnesane type sesquiterpenes compound and preparation method and medical application thereof

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN105294665A (en) * 2015-12-01 2016-02-03 吕涛 Novel diterpene compound for neuroprotection
CN105461782A (en) * 2016-01-14 2016-04-06 郑平珍 Novel triterpene compound and preparation and medical application thereof

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