CN105906683A - Ferric carboxymaltose injection and medical application thereof - Google Patents
Ferric carboxymaltose injection and medical application thereof Download PDFInfo
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- CN105906683A CN105906683A CN201610335324.XA CN201610335324A CN105906683A CN 105906683 A CN105906683 A CN 105906683A CN 201610335324 A CN201610335324 A CN 201610335324A CN 105906683 A CN105906683 A CN 105906683A
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J63/00—Steroids in which the cyclopenta(a)hydrophenanthrene skeleton has been modified by expansion of only one ring by one or two atoms
- C07J63/008—Expansion of ring D by one atom, e.g. D homo steroids
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7135—Compounds containing heavy metals
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0019—Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/08—Solutions
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/88—Liliopsida (monocotyledons)
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Abstract
The invention discloses a ferric carboxymaltose injection and medical application thereof. The ferric carboxymaltose injection contains ferric carboxymaltose and a novel-structure natural product compound (I). The ferric carboxymaltose and compound (I) can enhance the CD4<+> cell count, improve the immunologic function and regulate the immunologic balance when being independently used. The combination of the ferric carboxymaltose and compound (I) further enhances the treatment effects, and can be developed into injections for treating AIDS. Compared with the prior art, the injection has outstanding substantial characteristics and marked progress.
Description
Technical field
The invention belongs to biomedicine field, be specifically related to a kind of carboxyl maltose rail injection liquid and medical usage thereof.
Background technology
Carboxyl maltose ferrum is a kind of novel iron complex, with maltodextrin by iron ion stably complexation wherein, controls ferrum
Disengage, iron ion can be combined to play a role with iron transporter and ferritin, and prevents from discharging substantial amounts of free iron, reduce
Nitrous oxide is formed.Carboxyl maltose ferrum can be effectively improved mild to moderate Patients with iron deficiency anemia Hb and serum ferritin concentration.
Summary of the invention
It is an object of the invention to provide a kind of carboxyl maltose rail injection liquid and medical usage thereof.
The above-mentioned purpose of the present invention is achieved by techniques below scheme:
A kind of compound (I) with following structural formula,
A kind of carboxyl maltose rail injection liquid, including carboxyl maltose ferrum, compound as claimed in claim 1 (I) and medicine
Acceptable carrier on.
The preparation method of above-claimed cpd (I), comprises following operating procedure: Medulla Junci is pulverized by (a), with 75～85% second
Alcohol circumfluence distillation, united extraction liquid, it is concentrated into without alcohol taste, successively by petroleum ether, ethyl acetate and water saturated n-butyl alcohol extraction
Take, respectively obtain petroleum ether extract, acetic acid ethyl ester extract and n-butyl alcohol extract；B in () step (a), n-butyl alcohol takes
Thing macroporous resin remove impurity, first with 8 column volumes of 25% ethanol elution, then with 12 column volumes of 70% ethanol elution, collects
70% eluent, concentrating under reduced pressure obtains 70% ethanol elution concentrate；C in () step (b), 70% ethanol elution concentrate is with just
Phase silica gel separates, and obtains 4 groups with the methylene chloride-methanol gradient elution that volume ratio is 85:1,45:1,25:1 and 15:1 successively
Point；D in () step (c), component 4 separates further by purification on normal-phase silica gel, be 20:1,15:1 and 1:1 by volume ratio successively
Methylene chloride-methanol gradient elution obtains 3 components；In (e) step (d) component 2 with octadecylsilane be bonded anti-phase
Silica gel separates, and with the methanol aqueous solution isocratic elution that concentration expressed in percentage by volume is 72%, collects 10～16 column volume eluents, washes
De-liquid is concentrated under reduced pressure to give compound (I).
Further, in the preparation method of compound (I), step (a) is extracted with 80% alcohol heat reflux, united extraction liquid.
Further, in the preparation method of compound (I), described macroporous resin is D101 type macroporous adsorbent resin.
Further, in the preparation method of compound (I), step (a) replace ethyl acetate to extract with dichloromethane,
Obtain dichloromethane extract.
The above-claimed cpd (I) application in the medicine of preparation treatment acquired immune deficiency syndrome (AIDS).
The application in the medicine of preparation treatment acquired immune deficiency syndrome (AIDS) of the above-mentioned carboxyl maltose rail injection liquid.
Advantages of the present invention:
Containing carboxyl maltose ferrum and the natural product of a kind of novel structure, carboxylic in the carboxyl maltose rail injection liquid that the present invention provides
When base maltose ferrum and this natural product independent role, acquired immune deficiency syndrome (AIDS) had therapeutical effect；During the two synergy, to acquired immune deficiency syndrome (AIDS)
Therapeutic effect improve further, the medicine for the treatment of acquired immune deficiency syndrome (AIDS) can be developed into.
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.To the greatest extent
The present invention is explained in detail by pipe with reference to preferred embodiment, it will be understood by those within the art that, can be to the present invention
Technical scheme modify or equivalent, without deviating from the spirit and scope of technical solution of the present invention.
Embodiment 1: compound (I) separates preparation and structural identification
Separation method: Medulla Junci (2kg) is pulverized by (a), extracts (15L × 3 time) with 80% alcohol heat reflux, and merging carries
Take liquid, be concentrated into without alcohol taste (3L), successively with petroleum ether (3L × 3 time), ethyl acetate (3L × 3 time) and water saturation
N-butyl alcohol (3L × 3 time) extraction, respectively obtain petroleum ether extract, acetic acid ethyl ester extract and n-butyl alcohol extract；(b)
Acetic acid ethyl ester extract D101 type macroporous resin remove impurity in step (a), first with 8 column volumes of 25% ethanol elution, then uses
70% ethanol elution 12 column volume, collects 70% eluent, and concentrating under reduced pressure obtains 70% ethanol elution concentrate；(c) step
B in (), 70% ethanol elution concentrate purification on normal-phase silica gel separates, be 85:1 (10 column volumes), 45:1 by volume ratio successively
The methylene chloride-methanol gradient elution of (8 column volumes), 25:1 (10 column volumes) and 15:1 (8 column volumes) obtains 4
Individual component；D in () step (c), component 4 separates further by purification on normal-phase silica gel, be 20:1 (10 cylinders by volume ratio successively
Long-pending), the methylene chloride-methanol gradient elution of 15:1 (8 column volumes) and 1:1 (6 column volumes) obtain 3 components；(e)
The reverse phase silica gel that in step (d), component 2 is bonded by octadecylsilane separates, water-soluble with the methanol that concentration expressed in percentage by volume is 72%
Liquid isocratic elution, collects 10～16 column volume eluents, and eluent is concentrated under reduced pressure to give compound (I) (HPLC normalizing
Change purity more than 98%).
Structural identification: HR-ESI-MS shows [M+H]+For m/z 469.3282, can obtain molecular formula in conjunction with nuclear-magnetism feature is
C30H44O4, degree of unsaturation is 9.Hydrogen nuclear magnetic resonance modal data δH(ppm, CDCl3, 600MHz): H-1 (1.62, dd,
J=12.4,8.9Hz), H-1 (2.11, dd, J=12.4,3.6Hz), H-2 (5.82, ddd, J=10.9,8.9,3.6Hz),
H-3 (5.68, d, J=10.9Hz), H-5 (0.99, m), H-6 (1.52, m), H-6 (1.63, m), H-7 (1.78,
M), and H-7 (1.91, m), H-9 (2.55, s), H-16 (2.47, d, J=13.1Hz), H-16 (2.81, d, J=13.1Hz),
H-18 (2.86, d, J=11.5Hz), H-19 (1.73, m), H-21 (1.34, m), H-21 (1.57, m), H-22
(1.66, m), H-22 (1.74, m), H-23 (1.09, s), H-24 (1.06, s), H-25 (1.28, s),
H-26 (1.26, s), H-27 (1.36, s), H-28 (0.89, s), H-29 (0.85, d, J=6.3Hz), H-30 (1.23,
S), and 12-OH (6.38, s)；Carbon-13 nmr spectra data δC(ppm, CDCl3, 125MHz): 39.6 (CH2, 1-C),
124.3 (CH, 2-C), 139.2 (CH, 3-C), 35.4 (C, 4-C), 57.2 (CH, 5-C), 19.7 (CH2,
6-C), 36.4 (CH2, 7-C), 46.5 (C, 8-C), 58.7 (CH, 9-C), 46.4 (C, 10-C), 196.2
(C, 11-C), 144.8 (C, 12-C), 143.2 (C, 13-C), 58.6 (C, 14-C), 209.4 (C, 15-C),
54.3(CH2, 16-C), 53.4 (C, 17-C), 42.3 (CH, 18-C), 41.7 (CH, 19-C), 70.5 (C,
20-C), 35.8 (CH2, 21-C), 35.8 (CH2, 22-C), 26.6 (CH3, 23-C), 21.7 (CH3, 24-C),
15.7(CH3, 25-C), 19.7 (CH3, 26-C), 14.8 (CH3, 27-C), 19.3 (CH3, 28-C), 11.2
(CH3, 29-C), 29.4 (CH3, 30-C).Infrared spectrum shows that this compound contains alpha, beta-unsaturated carbonyl (1705cm-1),
Hydroxyl (3425cm-1), carbonyl (1760cm-1), double bond (1663cm-1) and gem-dimethyl (1380cm-1) group.13C-NMR、
DEPT and hsqc spectrum show 30 carbon signals, including eight methyl, six methylene, six methine (two alkene
Hydrocarbon carbon), and ten quaternary carbons (company's oxygen carbon, two carbonyls, a pair four substituted olefine carbon), function above structure is tied again
Close insatiable hunger sum and show that this compound is pentacyclic triterpene structure.1H-NMR spectrum combines seven unimodal onychostromas that hsqc spectrum shows
Subsignal δH1.09 (3H, s), 1.06 (3H, s), 1.28 (3H, s), 1.26 (3H, s), 1.36 (3H, s),
0.89 (3H, s) He 1.23 (3H, s), a bimodal methyl proton signal δH0.85 (3H, d, J=6.3Hz) and1H-NMR
Data show that this compound is Ursane triterpenoid compound.In this Ursane compound, C-11 and C-15 position is formed
Ketone group, C-2 Yu C-3, C-12 Yu C-13 form double bond structure.H in HMBC spectrum2-16 and H3-27 is relevant to C-15
Property and their carbon chemical shifts confirm C-15 the most further and form ketone group.H-9 and H-18 and C-12 in another HMBC spectrum,
H-18 and H3-27 and C-13,12-OH and C-12 coherent signal and their carbon chemical shifts show that this compound exists alkene
Alcohol of formula structure, hydroxyl is connected to the double bond composition enol-type structure that C-12 position is formed with C-12 and C-13.12-OH in HMBC spectrum
Confirm that C-11 position is carbonyl with coherent signal and the carbon chemical shifts of H-9 Yu C-11.Additionally, HMBC spectrum in H-18,
H-19、H3-29 and H3Coherent signal and the C-20 carbon chemical shifts of-30 and C-20 may determine that C-20 position is connected with a hydroxyl
Base.H in NOESY spectrum3-28 and H3-29 exist coherent signal with H-18, but H3-30 do not have coherent signal, table with H-18
The hydroxyl of bright C-20 position is beta comfiguration.Comprehensive hydrogen spectrum, carbon spectrum, HMBC spectrum and NOESY spectrum, and document is about associated class
Type nuclear magnetic data, can determine that this compound is as follows substantially, spatial configuration further by ECD test determine, theoretical value with
Experiment value is basically identical.
This compound chemical formula and carbon atoms numbered are as follows:
Embodiment 2: pharmacological action
1, materials and methods
1.1 animal
Rhesus Macacus 5～7kg, male and healthy, positive without SIV through PCR detection before infecting, routine blood test is normal, by Chinese medicine section
Institute of lab animals of institute provides.
1.2 reagent and sample
Carboxyl maltose ferrum is purchased from Nat'l Pharmaceutical & Biological Products Control Institute.Compound (I) is made by oneself, and preparation method is shown in embodiment 1.
Monoclonal antibody, purchased from Military Medical Science Institute's biological preparation centre of development.AZT (azidothymidine AZT) is purchased from Burroughs.
1.3 instrument
FACS420 type flow cytometer measures (B.D company of the U.S.).TMRMC type microplate reader.
Prepared by 1.4 monkey packets and model
SIVmac infects successfully animal random packet, respectively Normal group, model control group, positive controls (AZT
Group 50mg kg-1), carboxyl maltose ferrum group (80mg kg-1), compound (I) group (80mg kg-1), carboxyl Fructus Hordei Germinatus
Sugar ferrum and compound (I) compositions group [40mg kg-1Carboxyl maltose ferrum+40mg kg-1Compound (I)].After infection
Within 2 weeks, being administered, medicine group every day is according to above-mentioned dosed administration；Normal group, every day is to normal saline equivalent.Often group is given every day
Medicine once, intravenous injection.Administration time is 18 weeks, then dissects and carries out pathological observation.
1.5T lymphocyte subgroup determination experiment
With monoclonal antibody direct labelling animal peripheral blood CD4+, CD8+Cell, is operated by product description, uses FACS420
Type flow cytometer measures.MICROCOMPUTER PROCESSING analyzes positive rate, and calculates CD4+/CD8Cell ratio.
1.6MTT method observes T, B lymphocyte proliferation experiment
The most aseptic monkey venous blood 2ml that takes, anticoagulant heparin, separate mononuclearcell, adjust cell number 1 × 105/ml.2. will adjust
Cell suspension is planted in 96 well culture plates, 200 μ l/ holes, and is separately added into different mitogen induction of lymphocyte differentiation,
ConA5 μ g/ml, LPS30 μ g/ml concentration, adds MTT (5mg/ml) and continues to cultivate 4h, add acidifying different after cultivating 48h
Propanol (0.04mol/L), utilizes TMRMC type microplate reader to detect, wavelength 570～630nm.
1.7 statistical method
Experimental data mean ± standard deviation (x ± s) represents, application SPSS18.0 version statistical software carry out one factor analysis of variance and
T checks, statistically significant for difference with P ＜ 0.05.
2, experimental result
2.1 couples of SIV infection animal CD4+The impact of cell
Application direct fluorescent labeling CD of monoclonal antibody4+, CD8+Cell, flow cytomery, result shows that SIVmac feels
Model control group CD when contaminating 4 weeks4+And CD4+/CD8+Ratio declines (P ＜ 0.01)；With model control group ratio, carboxyl maltose
Ferrum and compound (I) compositions group and positive controls CD4+And CD4+/CD8+Ratio significantly rises (P ＜ 0.01)；With mould
Type group ratio, carboxyl maltose ferrum group, compound (I) group CD4+And CD4+/CD8+Ratio rises (P ＜ 0.05).See table.
2.2 impacts on SIV animal pattern T lymphocyte differentiation propagation
With Normal group ratio, model group is when infecting 4 weeks, and ConA induction differentiation and proliferation significant reaction is declined by T cell,
Notable difference (P < 0.01) is had compared with before infection.Compare with model group, carboxyl maltose ferrum and compound (I) compositions
The respond of mitosis primary stimuli is significantly improved by group and positive controls T cell, T cell rebound significantly (P ＜ 0.01)；
With model group ratio, carboxyl maltose ferrum group, compound (I) group T cell gos up (P ＜ 0.05).Result see table.
2.3 impacts on SIV animal pattern bone-marrow-derived lymphocyte differentiation and proliferation
Comparing with Normal group, model control group is when infecting 4 weeks, and B cell function is impaired compared with before infection, and propagation is anti-
Should be less than before infecting (P < 0.01).Compare with model control group, carboxyl maltose ferrum and compound (I) compositions group and sun
Property matched group B cell proliferation significantly rises (P ＜ 0.01)；Compare with model control group, carboxyl maltose ferrum group, compound (I)
Group B cell proliferation rises (P ＜ 0.05).Result see table.
Acquired immune deficiency syndrome (AIDS) is also known as acquired immune deficiency syndrome (AIDS), caused by HIV (human immunodeficiency virus) infection, uses Hart therapy the most in the world
(HAART), the most several mutual supplement with each other's advantages Western medicine use in conjunction, the HAART medicine being well recognized as, but
Virus can not be made thoroughly to kill, and side effect is many, make patients ' life quality decline.Simian immunodeficiency virus (SIV) induction monkey
Acquired immune deficiency syndrome (AIDS) (SAIDS) infected animal model, is to recommend anti-AIDS drug to treat animal mould through WHO expert in 1989
Type, it is in nosetiology, and the aspect such as clinic, pathology, immunology and pathogeny is very much like with people's aids infection, the most
Relatively it is used for evaluating the effect of anti-AIDS drug.
CD4+Cell is the important cells safeguarding body's immunity, is also the main cell of SIV destruction, therefore CD4+Positive
Cell number reduces has direct relation to immunodeficiency progress.Its quantity and changes of function are to evaluate disease development and curative effect of medication
Important indicator.Normal human CD4+Cell and CD8+Cell restricts the immunologic balance maintaining body relatively, owing to HIVAIDS suffers from
Person CD4+Cell quantity constantly reduces and function is impaired to making CD4+CD8+Cell proportion is inverted, CD8+Cell relatively CD4+Cell
Relatively preponderate, strengthen immunosuppressive action, cause immune dysfunction, invade other immunocyte of body such as HIV further,
I.e. can cause body's immunity defect.Due to the most continual duplication of virus, destroy immune cell, cause SIV
Animal pattern peripheral blood CD4+Cell quantity substantially reduces.CD4+Cell is destroyed, and quantity reduces, lymphocyte normal function
Being suppressed, cause T lymphocyte to reduce mitogen induced reaction ability, taint with SIV animal B-cells is many to antibacterial fat
Sugar LPS respond also declines, but obvious not as good as T cell, in slow downward trend.
The above results shows, when carboxyl maltose ferrum, compound (I) independent role, can improve CD4+Cell number and changing
Kind immunologic function adjusts immunologic balance, and acquired immune deficiency syndrome (AIDS) is had therapeutical effect；Carboxyl maltose ferrum and compound (I) synergy
Time, therapeutic effect improves further, can develop into the injection for the treatment of acquired immune deficiency syndrome (AIDS).
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, technical scheme can be modified or equivalent, and not take off
Essence and protection domain from technical solution of the present invention.
Claims (8)
1. a compound (I) with following structural formula,
2. a carboxyl maltose rail injection liquid, it is characterised in that: include carboxyl maltose ferrum, change as claimed in claim 1
Compound (I) and pharmaceutically acceptable carrier.
3. the preparation method of the compound (I) described in claim 1, it is characterised in that comprise following operating procedure: (a)
By Medulla Junci pulverize, with 75～85% alcohol heat reflux extract, united extraction liquid, be concentrated into without alcohol taste, successively use petroleum ether, second
Acetoacetic ester and water saturated n-butanol extraction, respectively obtain petroleum ether extract, acetic acid ethyl ester extract and n-butyl alcohol extract；
B in () step (a), n-butyl alcohol takes thing macroporous resin remove impurity, first with 8 column volumes of 25% ethanol elution, then use 70% second
12 column volumes of alcohol eluting, collect 70% eluent, and concentrating under reduced pressure obtains 70% ethanol elution concentrate；In (c) step (b)
70% ethanol elution concentrate with purification on normal-phase silica gel separate, successively with the dichloromethane that volume ratio is 85:1,45:1,25:1 and 15:1-
Methanol elution gradient obtains 4 components；D in () step (c), component 4 separates further by purification on normal-phase silica gel, use volume successively
3 components are obtained than the methylene chloride-methanol gradient elution for 20:1,15:1 and 1:1；E in () step (d), component 2 is used
The reverse phase silica gel of octadecylsilane bonding separates, and with the methanol aqueous solution isocratic elution that concentration expressed in percentage by volume is 72%, collects
10～16 column volume eluents, eluent is concentrated under reduced pressure to give compound (I).
The preparation method of compound the most according to claim 3 (I), it is characterised in that: step (a) 80% second
Alcohol circumfluence distillation, united extraction liquid.
The preparation method of compound the most according to claim 3 (I), it is characterised in that: described macroporous resin is D101
Type macroporous adsorbent resin.
The preparation method of compound the most according to claim 3 (I), it is characterised in that: step (a) is used dichloromethane
Alkane replaces ethyl acetate to extract, and obtains dichloromethane extract.
7. the application in the medicine of preparation treatment acquired immune deficiency syndrome (AIDS) of the compound (I) described in claim 1.
8. the application in the medicine of preparation treatment acquired immune deficiency syndrome (AIDS) of the carboxyl maltose rail injection liquid described in claim 2.
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Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106008543A (en) * | 2016-05-25 | 2016-10-12 | 杭州更蓝生物科技有限公司 | Novel diterpenoid compound and preparation method thereof |
| CN106046112A (en) * | 2016-06-24 | 2016-10-26 | 胡逸穹 | Diflunisal pharmaceutical composition and medical application thereof |
| CN106074499A (en) * | 2016-06-02 | 2016-11-09 | 杭州更蓝生物科技有限公司 | The application in medicine of a kind of Crow alkane type diterpene-kind compound |
| CN106187773A (en) * | 2016-07-04 | 2016-12-07 | 郑飞珍 | A kind of new labdane diterpenes compound and preparation method thereof and medical usage |
| CN106279344A (en) * | 2016-08-14 | 2017-01-04 | 吴芊葭 | A kind of native compound separated from Radix Saposhnikoviae and preparation method thereof, medical applications |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105017375A (en) * | 2015-08-14 | 2015-11-04 | 河南大学 | Anticoagulation blackberry seed effective component and extraction and separation method and application thereof |
-
2016
- 2016-05-18 CN CN201610335324.XA patent/CN105906683A/en active Pending
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105017375A (en) * | 2015-08-14 | 2015-11-04 | 河南大学 | Anticoagulation blackberry seed effective component and extraction and separation method and application thereof |
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106008543A (en) * | 2016-05-25 | 2016-10-12 | 杭州更蓝生物科技有限公司 | Novel diterpenoid compound and preparation method thereof |
| CN106074499A (en) * | 2016-06-02 | 2016-11-09 | 杭州更蓝生物科技有限公司 | The application in medicine of a kind of Crow alkane type diterpene-kind compound |
| CN106046112A (en) * | 2016-06-24 | 2016-10-26 | 胡逸穹 | Diflunisal pharmaceutical composition and medical application thereof |
| CN106187773A (en) * | 2016-07-04 | 2016-12-07 | 郑飞珍 | A kind of new labdane diterpenes compound and preparation method thereof and medical usage |
| CN106279344A (en) * | 2016-08-14 | 2017-01-04 | 吴芊葭 | A kind of native compound separated from Radix Saposhnikoviae and preparation method thereof, medical applications |
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