CN105820144A - Pharmaceutical composition of cefdinir and medical application thereof - Google Patents
Pharmaceutical composition of cefdinir and medical application thereof Download PDFInfo
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- CN105820144A CN105820144A CN201610258309.XA CN201610258309A CN105820144A CN 105820144 A CN105820144 A CN 105820144A CN 201610258309 A CN201610258309 A CN 201610258309A CN 105820144 A CN105820144 A CN 105820144A
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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
- A61K31/33—Heterocyclic compounds
- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
- A61K31/34—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having five-membered rings with one oxygen as the only ring hetero atom, e.g. isosorbide
- A61K31/343—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having five-membered rings with one oxygen as the only ring hetero atom, e.g. isosorbide condensed with a carbocyclic ring, e.g. coumaran, bufuralol, befunolol, clobenfurol, amiodarone
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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
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/54—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one sulfur as the ring hetero atoms, e.g. sulthiame
- A61K31/542—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one sulfur as the ring hetero atoms, e.g. sulthiame ortho- or peri-condensed with heterocyclic ring systems
- A61K31/545—Compounds containing 5-thia-1-azabicyclo [4.2.0] octane ring systems, i.e. compounds containing a ring system of the formula:, e.g. cephalosporins, cefaclor, or cephalexine
- A61K31/546—Compounds containing 5-thia-1-azabicyclo [4.2.0] octane ring systems, i.e. compounds containing a ring system of the formula:, e.g. cephalosporins, cefaclor, or cephalexine containing further heterocyclic rings, e.g. cephalothin
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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
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Abstract
The invention discloses a pharmaceutical composition of cefdinir and medical application thereof. The pharmaceutical composition of cefdinir contains cefdinir and a novel-structure natural product compound (I). The cefdinir and compound (I) can obviously enhance the neural function score of the ischemia-reperfusion rat and obviously lower the expression level of the inflammatory cell factor TNF-alpha, IL-1beta and adhesion molecules VCAM-1 and ICAM-1; and the combination of the cefdinir and compound (I) has better effects than the single use of the cefdinir or compound (I), and can be developed into drugs for protecting ischemia reperfusion injuries.
Description
Technical field
The invention belongs to biomedicine field, relate to the new application of cefdinir, be specifically related to cefdinir pharmaceutical composition and
Its medical usage.
Background technology
Cefdinir is for the staphylococcus sensitive to cefdinir, Streptococcus, streptococcus pneumoniae, peptostreptococcus, propanoic acid
Bacillus, gonococcus, moraxelle catarrhalis, escherichia coli, Klebsiella, proteus mirabilis, Pu Luweidengsi
Infection caused by the bacterial strain such as Pseudomonas, hemophilus influenza.
Only ischemia is also not enough to cause tissue injury to have many evidences to illustrate, but recovers the most suddenly to supply after ischemia a period of time
Damage just occurs during blood (i.e. Reperfu-sion).At traumatic shock, surgical operation, organ transplantation, burn, cold injury and thrombosis etc.
During disturbance of blood circulation, postischemic reperfusion damage all can occur.The blood capillary caused during ischemic tissue's Reperfu-sion and organa parenchymatosum
Damage mainly caused by reactive oxygen free radical, this proof obtained in multiple organ.Ischemic tissue have clear
Except the antioxidant reductase synthesis capability generation obstacle of free radical, thus exacerbate the damage of radical pair postischemic reperfusion tissue.
SOD is used to remove the protected effect of radical pair ischemic reperfusion tissue injury.
Up to now, there is not yet the dependency report of cefdinir and pharmaceutical composition thereof and cerebral ischemia reperfusion injury.
Summary of the invention
It is an object of the invention to provide the pharmaceutical composition of a kind of cefdinir, containing cefdinir and in this pharmaceutical composition
Planting natural product, cefdinir and this natural product can be with coordinating protection cerebral ischemia reperfusion injury.
The above-mentioned purpose of the present invention is achieved by techniques below scheme:
A kind of compound (I) with following structural formula,
The pharmaceutical composition of a kind of cefdinir, including cefdinir, compound as claimed in claim 1 (I) and pharmacy
Upper acceptable carrier, is prepared as the dosage form needed.
Further, pharmaceutically acceptable carrier includes diluent, excipient, filler, binding agent, wetting agent, collapses
Solve agent, absorption enhancer, surfactant, absorption carrier or lubricant.
Further, described dosage form include tablet, capsule, oral liquid, suck agent, granule, electuary, pill, powder,
Unguentum, sublimed preparation, suspensoid, powder, solution, injection, suppository, spray, drop or patch.
The preparation method of above-claimed cpd (I), comprises following operating procedure: Herba Ardisiae Japonicae is pulverized by (a), with 80～90% 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 6 column volumes of 30% ethanol elution, then with 12 column volumes of 85% ethanol elution, collects
85% eluent, concentrating under reduced pressure obtains 85% ethanol elution concentrate；C in () step (b), 85% ethanol elution concentrate is with just
Phase silica gel separates, and obtains 4 with the methylene chloride-methanol gradient elution that volume ratio is 100:1,50:1,25:1 and 12:1 successively
Component；D in () step (c), component 4 separates further by purification on normal-phase silica gel, be 20:1,12:1 and 2:1 by volume ratio successively
Methylene chloride-methanol gradient elution obtain 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 88%, collects 13～16 column volume eluents,
Eluent is concentrated under reduced pressure to give compound (I).
Further, in the preparation method of compound (I), step (a) is extracted with 85% 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 protection cerebral ischemia reperfusion injury.
The application in the medicine of preparation protection cerebral ischemia reperfusion injury of the pharmaceutical composition of above-mentioned cefdinir.
Advantages of the present invention:
Containing cefdinir and the natural product of a kind of novel structure, cephalo in the pharmaceutical composition of the cefdinir that the present invention provides
When ground Buddhist nun and this natural product independent role, cerebral ischemia reperfusion injury had protective effect；During the two synergy, to brain
The protected effect of ischemical reperfusion injury improves further, can develop into the medicine of protection cerebral ischemia reperfusion injury.The present invention
Compared with prior art there is prominent substantive distinguishing features and significantly progress.
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
Reagent source: ethanol, petroleum ether, ethyl acetate, n-butyl alcohol, dichloromethane are analytical pure, purchased from Shanghai Ling Feng chemistry
Reagent company limited, methanol, analytical pure, purchased from Jiangsu Han Bang chemical reagent company limited.
Separation method: Herba Ardisiae Japonicae (2kg) is pulverized by (a), extracts (15L × 3 time) with 85% 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 6 column volumes of 30% ethanol elution, then uses
85% ethanol elution 12 column volume, collects 85% eluent, and concentrating under reduced pressure obtains 85% ethanol elution concentrate；(c) step
B in (), 85% ethanol elution concentrate purification on normal-phase silica gel separates, be 100:1 (12 column volumes), 50:1 by volume ratio successively
The methylene chloride-methanol gradient elution of (10 column volumes), 25:1 (8 column volumes) and 12:1 (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 (6 cylinders by volume ratio successively
Long-pending), the methylene chloride-methanol gradient elution of 12:1 (8 column volumes) and 2:1 (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 88%
Liquid isocratic elution, collects 13～16 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 317.2073, can obtain molecular formula in conjunction with nuclear-magnetism feature is
C20H28O3, degree of unsaturation is 7.Hydrogen nuclear magnetic resonance modal data δH(ppm, pyridine-d5, 500MHz): H-1 (6.46,
Dd, J=4.8,10.6Hz), H-2a (3.39, m), H-2b (3.10, m), H-3 (6.85, m), H-5a (3.23,
D, J=15.6Hz), H-5b (2.98, dd, J=15.6,9.3Hz), H-6 (5.06, dd, J=9.3,1.4Hz), H-7
(1.87, m), H-8 (1.46, m), H-9a (2.13, dd, J=16.1,2.6Hz), H-9b (1.67, dd, J=16.1,
7.3Hz), and H-11 (1.80, m), H-12 (0.93, d, J=5.7Hz), H-13 (1.13, d, J=5.7Hz), H-14
(1.19, d, J=6.8Hz), and H-3 ' (7.01, m), H-4 ' (1.65, d, J=7.3Hz), H-5 ' (1.84, s)；Core
Magnetic resonance carbon modal data δC(ppm, pyridine-d5, 125MHz): 132.4 (CH, 1-C), 29.6 (CH2, 2-C)
131.7 (CH, 3-C), 132.4 (C, 4-C), 28.3 (CH2, 5-C), 77.4 (CH, 6-C), 52.7 (CH,
7-C), 22.4 (CH, 8-C), 32.5 (CH2, 9-C), 158.6 (C, 10-C), 26.4 (CH, 11-C), 22.1
(CH3, 12-C), 23.8 (CH3, 13-C), 18.4 (CH3, 14-C), 171.2 (C, 15-C), 201.1 (C,
1 '-C), 128.8 (C, 2 '-C), 138.5 (CH, 3 '-C), 14.7 (CH3, 4 '-C), 13.3 (CH3, 5 '-C).
1756cm in infrared spectrum-1236nm absorption band during absorption band is composed with UV shows that this compound contains α, β-unsaturated lactone
Structure, the 1714cm in infrared spectrum-1With 1682cm-1Absorption band shows to there is ketone group and double bond fragment in structure.13C-NMR、
DEPT and hsqc spectrum show 20 carbon signals, including five methyl, three methylene, seven methine (companies
Oxygen carbon and three alkene carbon), and five quaternary carbons (two carbonyl carbon and three alkene carbon), function above structure is not in conjunction with
Saturated number shows that this compound is twin nuclei.1H-NMR spectrum combines hsqc spectrum and shows five methyl proton signal δH 0.93
(3H, d, J=5.7Hz), 1.13 (3H, d, J=5.7Hz), 1.19 (3H, d, J=6.8Hz), 1.65 (3H, d,
J=7.3Hz), 1.84 (3H, s), three groups of methene proton signal δH3.39 (1H, m) with 3.10 (1H, m), 3.23
(1H, d, J=15.6Hz) and 2.98 (1H, dd, J=15.6,9.3Hz), 2.13 (1H, dd, J=16.1,2.6Hz)
With 1.67 (1H, dd, J=16.1,7.3Hz), three olefinic proton signals δH6.46 (1H, dd, J=4.8,10.6Hz),
6.85 (1H, m) with 7.01 (1H, m), an even oxygen methine proton signal δH5.06 (1H, dd, J=9.3,1.4Hz),
Three methine proton signal δH1.87 (1H, m), 1.46 (1H, m), 1.80 (1H, m).1H-1H COSY composes
In there is H-1/H2-2/H-3、H2-5/H-6/H-7/H-8/H2-9、H-7/H-11/H3-12、H-11/H3-13 and H-8/H3-14 phases
OFF signal, the H of display in composing in conjunction with HMBC2-2 and H2-9 and C-1 and H2-2、H2-5 and H-6 Yu C-4 coherent signals
Germacrane sesquiterpene skeleton can be built.In HMBC spectrum, H-3 ' and C-2 ' and C-4 ' coherent signal can build 2 '-methyl-2 '-
.DELTA.3-2-butenone substrate section.Additionally HMBC composes H-3, H2Exist between-5 and H-6 and C-15 coherent signal hint C-6 and C-15
One lactonic ring structure.In NOESY spectrum, H-8 is beta comfiguration, H-9b Yu H-8 exists coherent signal, so H-9a and H-2a
And the dependency of H-9a Yu H-5a shows that H-2a, H-5a and H-9a are all α configuration, simultaneously H-2a Yu H-5a coherent signal
Show Δ3(4)Double bond is E.Comprehensive hydrogen spectrum, carbon spectrum, HMBC spectrum and NOESY spectrum, and document is about correlation type
Nuclear magnetic data, can determine that this compound is as follows substantially, and spatial configuration is determined by ECD test further, theoretical value and reality
Test value basically identical.This compound chemical formula and carbon atoms numbered are as follows:
Embodiment 2: pharmacological action
1, materials and methods
1.1 animal
60 adult healthy male Sprague-Dawley (SD) rats, SPF level, body weight 280-300g, Beijing tie up tonneau
Laboratory animal Technology Co., Ltd. of China provides.In experimentation, the feeding environment of rat is stable, and room temperature (25 ± 2) DEG C is the wettest
Degree (55 ± 5) %, day alternates with night for signal light control 12h.
1.2 reagent and sample
Cefdinir is purchased from National Institute for Food and Drugs Control.Compound (I) is made by oneself, and preparation method is shown in embodiment 1.Depend on
Da Lafeng injection (Sino Pharm Group Guorui Pharmaceutical Co., Ltd).Rabbit anti-Mus GFAP antibody, rabbit anti-Mus Iba1 antibody is purchased from Vector
Company；Rabbit anti-Mus TNF-α antibody, rabbit anti-Mus IL-1 β, rabbit anti-Mus VCAM-1 antibody, rabbit anti-Mus ICAM-1 antibody are purchased from
San-ta-Cruz；Horseradish peroxidase-labeled goat anti-rabbit igg is purchased from Pierce Biotechnology company of the U.S..
1.3 instrument
SZX16 type microscope (Olympus company of Japan)；Freezing microtome (Lycra, Germany)；PowerGen 125 type
Tissue refiner (Sai Mo fly generation you company)；GS-15R centrifuge (Beckinan company, the U.S.).
1.4 animal packets and administration
60 adult healthy male SD rats, are randomly divided into sham operated rats, ischemia-reperfusion injury model group, Yi Dalafeng administration group
(3mg·kg-1), cefdinir group (20mg kg-1), compound (I) group (20mg kg-1), cefdinir and chemical combination
Thing (I) compositions group [10mg kg-1Cefdinir+10mg kg-1Compound (I)], often group 10.Respectively organize respectively
At once being administered by tail vein injection in Reperfu-sion, sham operated rats and model group give 2ml normal saline.
1.5MCAO method sets up Cerebral Ischemia Reperfusion model
The preoperative 12h fasting of SD rat, 10% chloral hydrate (350mg kg-1) intraperitoneal injection of anesthesia, dorsal position is fixed.Reference
The middle cerebral artery line brush of Longa etc., causes left side middle cerebral artery occlusion.After ischemia 2h, neck will be drawn out to outside bolt alignment
Inside realize Reperfu-sion.Sham operated rats only carries out preoperative anesthesia and blood vessel exclusion, does not ligatures and lead-in wire bolt.
1.6 neurological deficits score
Rat animal behavioral study is carried out after Reperfu-sion 24h.The 5 grades 4 points systems with reference to Longa etc.: 0 point, impassivity merit
Symptom can be lacked；1 point, it is impossible to full extension offside fore paw；2 points, when creeping, occur that offside is turn-taked；3 points, to right during walking
Roll；4 points, it is impossible to spontaneous walking, loss of consciousness.
1.7Western Blot detects TNF-α, the expression of IL-1 β, VCAM-1, ICAM-1
After animal row I/R operation 24h, 4% paraformaldehyde perfusion is fixing, and broken end takes brain, crown cut anterior fontanelle before 1.0mm to the most front
After chimney, the cerebral tissue of 3.0mm, is homogenized.Protein lysate cracking, then 12000r min at 4 DEG C is added on ice-1From
Heart 5min, carries out the mensuration of protein content, SDS-PAGE electrophoresis, transferring film, closes, TNF-α (1:500), IL-1 β (1:
200), VCAM-1 (1:200), ICAM-1 (1:200) resist and hatch TBST after 24h at 4 DEG C and wash 3 times；Two
Hatch 1h, ECL chemiluminescence for anti-37 DEG C, scotography, fixing, film is scanned and takes pictures and be analyzed.
1.8 statistical method
Experimental data SPSS 11.5 statistical software analysis, acquired results represents with x ± s, and between group, the comparison of mean uses t inspection,
The comparison of more than 2 groups means uses variance analysis, and P < 0.05 is that difference is statistically significant.
2 experimental results
2.1 impacts on rats after cerebral ischemic reperfusion nervous symptoms
Reperfu-sion 24h, each group rat is without death, and model group rats shows serious neurologic impairment (P < 0.01), chemical combination
Thing (I) group, cefdinir group, Edaravone group all can significantly reduce nervous lesion that ischemia-reperfusion causes (P < 0.05,
P < 0.05, P < 0.05), cefdinir and compound (I) group effect are more notable, P < 0.01.It is shown in Table 1.
The table 1 impact on rats after cerebral ischemic reperfusion nervous symptoms
| Group | Neuroscore |
| Sham operated rats | 0.00±0.00 |
| Model control group | 2.68±0.46 |
| Edaravone group | 1.59±0.37 |
| Cefdinir group | 1.56±0.36 |
| Compound (I) group | 1.55±0.37 |
| Cefdinir and compound (I) compositions group | 1.25±0.31 |
2.2 impacts that rats after cerebral ischemic reperfusion TNF-α, IL-1 β, VCAM-1, ICAM-1 are expressed
After Cerebral Ischemia/Reperfusion 24h, cytokine TNF-α, IL-1 β and adhesion molecules VCAM-1 in the cortical tissue of ischemic region,
ICAM-1 protein expression dramatically increases, cefdinir group, compound (I) group be administered in early days after ischemia for TNF-α, IL-1 β,
The expression of VCAM-1, ICAM-1 all has inhibitory action in various degree, significant difference (P < 0.05)；Cefdinir and chemical combination
Thing (I) compositions group suppresses each protein expression (P < 0.01) further, and effect is more notable.It is shown in Table 2.
TNF-α, IL-1 β, VCAM-1, ICAM-1 expressing quantity in table 2 Ge Zu rat cerebral tissue
| Group | TNF-α | IL-1β | VCAM-1 | ICAM-1 |
| Sham operated rats | 0.35 | 0.53 | 0.09 | 0.08 |
| Model control group | 1.24 | 1.16 | 0.69 | 0.69 |
| Edaravone group | 0.62 | 0.76 | 0.36 | 0.27 |
| Cefdinir group | 0.69 | 0.73 | 0.35 | 0.24 |
| Compound (I) group | 0.66 | 0.66 | 0.33 | 0.25 |
| Cefdinir and compound (I) compositions group | 0.46 | 0.44 | 0.17 | 0.12 |
Result above shows, cefdinir, compound (I) all can significantly improve the function of nervous system of rats after cerebral ischemic reperfusion and comment
Divide and substantially reduce inflammatory cytokine TNF-α, IL-1 β and adhesion molecules VCAM-1, the expression of ICAM-1, both
Share effect and be better than alone, can be developed into protecting the medicine of cerebral ischemia reperfusion injury.
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.
Technical solution of the present invention is modified or equivalent is without departing from the essence of technical solution of the present invention and protection domain.
Claims (10)
1. a compound (I) with following structural formula,
2. the pharmaceutical composition of a cefdinir, it is characterised in that: include cefdinir, chemical combination as claimed in claim 1
Thing (I) and pharmaceutically acceptable carrier, be prepared as the dosage form needed.
The pharmaceutical composition of cefdinir the most according to claim 2, it is characterised in that: pharmaceutically acceptable carrier
Including diluent, excipient, filler, binding agent, wetting agent, disintegrating agent, absorption enhancer, surfactant, absorption
Carrier or lubricant.
The pharmaceutical composition of cefdinir the most according to claim 2, it is characterised in that: described dosage form includes tablet, glue
Wafer, oral liquid, suck agent, granule, electuary, pill, powder, unguentum, sublimed preparation, suspensoid, powder, solution,
Injection, suppository, spray, drop or patch.
5. the preparation method of the compound (I) described in claim 1, it is characterised in that comprise following operating procedure: (a)
By Herba Ardisiae Japonicae pulverize, with 80～90% 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 6 column volumes of 30% ethanol elution, then use 85% second
12 column volumes of alcohol eluting, collect 85% eluent, and concentrating under reduced pressure obtains 85% ethanol elution concentrate；In (c) step (b)
85% ethanol elution concentrate purification on normal-phase silica gel separates, and is the dichloromethane of 100:1,50:1,25:1 and 12:1 by volume ratio successively
-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 20:1,12:1 and 2:1；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 88%, collects
13～16 column volume eluents, eluent is concentrated under reduced pressure to give compound (I).
The preparation method of compound the most according to claim 5 (I), it is characterised in that: step (a) 85% second
Alcohol circumfluence distillation, united extraction liquid.
The preparation method of compound the most according to claim 5 (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 5 (I), it is characterised in that: step (a) is used dichloromethane
Alkane replaces ethyl acetate to extract, and obtains dichloromethane extract.
9. the application in the medicine of preparation protection cerebral ischemia reperfusion injury of the compound (I) described in claim 1.
10. the pharmaceutical composition of the arbitrary described cefdinir of claim 2～4 is at the medicine of preparation protection cerebral ischemia reperfusion injury
Application in thing.
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105777849A (en) * | 2016-04-23 | 2016-07-20 | 何淑琼 | Pharmaceutical composition of butorphanol tartrate and medical application thereof |
| CN106083800A (en) * | 2016-06-13 | 2016-11-09 | 崔坤峰 | The pharmaceutical composition of chlorprothixene and the protective effect to cerebral ischemia reperfusion injury |
| WO2017215676A1 (en) * | 2016-06-13 | 2017-12-21 | 赵吉永 | Carbidopa pharmaceutical composition and medical use thereof for treating liver cancer |
-
2016
- 2016-04-23 CN CN201610258309.XA patent/CN105820144A/en not_active Withdrawn
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105777849A (en) * | 2016-04-23 | 2016-07-20 | 何淑琼 | Pharmaceutical composition of butorphanol tartrate and medical application thereof |
| CN106083800A (en) * | 2016-06-13 | 2016-11-09 | 崔坤峰 | The pharmaceutical composition of chlorprothixene and the protective effect to cerebral ischemia reperfusion injury |
| WO2017215676A1 (en) * | 2016-06-13 | 2017-12-21 | 赵吉永 | Carbidopa pharmaceutical composition and medical use thereof for treating liver cancer |
| WO2017215680A3 (en) * | 2016-06-13 | 2018-02-15 | 赵吉永 | Chlorprothixene pharmaceutical composition and effects thereof for protecting cerebral ischemia reperfusion injuries |
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Application publication date: 20160803 |