CN103638015A - Application of Manzamenone O in platelet aggregation inhibitor - Google Patents
Application of Manzamenone O in platelet aggregation inhibitor Download PDFInfo
- Publication number
- CN103638015A CN103638015A CN201310624207.1A CN201310624207A CN103638015A CN 103638015 A CN103638015 A CN 103638015A CN 201310624207 A CN201310624207 A CN 201310624207A CN 103638015 A CN103638015 A CN 103638015A
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- CN
- China
- Prior art keywords
- manzamenone
- platelet aggregation
- application
- aggregation inhibitor
- platelet
- 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.)
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- MQOSGVWARDSXKJ-PDOPHQTESA-N methyl (3S,3aR,4R,6S,7R)-3-[(3aR,5S,6aS)-5-hexadecyl-5-hydroxy-2-oxo-6,6a-dihydro-3H-furo[3,2-b]furan-3a-yl]-4-heptadecanoyl-6-hydroxy-6-methyl-2-oxo-7-pentadecyl-3a,4,5,7-tetrahydro-3H-indene-1-carboxylate Chemical compound CCCCCCCCCCCCCCCCC(=O)[C@@H]1C[C@](C)(O)[C@H](CCCCCCCCCCCCCCC)C2=C(C(=O)OC)C(=O)[C@H]([C@@]34[C@@H](OC(=O)C3)C[C@](O)(CCCCCCCCCCCCCCCC)O4)[C@@H]12 MQOSGVWARDSXKJ-PDOPHQTESA-N 0.000 title claims abstract description 60
- 229940127218 antiplatelet drug Drugs 0.000 title abstract description 4
- 101000783577 Dendroaspis angusticeps Thrombostatin Proteins 0.000 title abstract 3
- 101000783578 Dendroaspis jamesoni kaimosae Dendroaspin Proteins 0.000 title abstract 3
- 239000000106 platelet aggregation inhibitor Substances 0.000 title abstract 3
- 208000010110 spontaneous platelet aggregation Diseases 0.000 claims abstract description 17
- 239000003814 drug Substances 0.000 claims description 13
- 238000002360 preparation method Methods 0.000 abstract description 5
- 230000000694 effects Effects 0.000 abstract description 2
- 150000001875 compounds Chemical class 0.000 description 10
- 239000003146 anticoagulant agent Substances 0.000 description 6
- BSYNRYMUTXBXSQ-UHFFFAOYSA-N Aspirin Chemical compound CC(=O)OC1=CC=CC=C1C(O)=O BSYNRYMUTXBXSQ-UHFFFAOYSA-N 0.000 description 5
- 210000004369 blood Anatomy 0.000 description 5
- 239000008280 blood Substances 0.000 description 5
- 229940079593 drug Drugs 0.000 description 5
- 239000005552 B01AC04 - Clopidogrel Substances 0.000 description 4
- 229940127219 anticoagulant drug Drugs 0.000 description 4
- GKTWGGQPFAXNFI-HNNXBMFYSA-N clopidogrel Chemical compound C1([C@H](N2CC=3C=CSC=3CC2)C(=O)OC)=CC=CC=C1Cl GKTWGGQPFAXNFI-HNNXBMFYSA-N 0.000 description 4
- 229960003009 clopidogrel Drugs 0.000 description 4
- 238000002474 experimental method Methods 0.000 description 4
- 241001668508 Plakortis Species 0.000 description 3
- 229960001138 acetylsalicylic acid Drugs 0.000 description 3
- 235000014113 dietary fatty acids Nutrition 0.000 description 3
- 229930195729 fatty acid Natural products 0.000 description 3
- 239000000194 fatty acid Substances 0.000 description 3
- 150000004665 fatty acids Chemical class 0.000 description 3
- 241001465754 Metazoa Species 0.000 description 2
- 206010050661 Platelet aggregation inhibition Diseases 0.000 description 2
- 241000700159 Rattus Species 0.000 description 2
- 208000007536 Thrombosis Diseases 0.000 description 2
- 230000002776 aggregation Effects 0.000 description 2
- 238000004220 aggregation Methods 0.000 description 2
- 230000000702 anti-platelet effect Effects 0.000 description 2
- 208000026106 cerebrovascular disease Diseases 0.000 description 2
- 238000000034 method Methods 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- 210000004623 platelet-rich plasma Anatomy 0.000 description 2
- QZAYGJVTTNCVMB-UHFFFAOYSA-N serotonin Chemical compound C1=C(O)C=C2C(CCN)=CNC2=C1 QZAYGJVTTNCVMB-UHFFFAOYSA-N 0.000 description 2
- 206010002383 Angina Pectoris Diseases 0.000 description 1
- 208000024172 Cardiovascular disease Diseases 0.000 description 1
- 206010008111 Cerebral haemorrhage Diseases 0.000 description 1
- 239000004375 Dextrin Substances 0.000 description 1
- 229920001353 Dextrin Polymers 0.000 description 1
- 102000009123 Fibrin Human genes 0.000 description 1
- 108010073385 Fibrin Proteins 0.000 description 1
- BWGVNKXGVNDBDI-UHFFFAOYSA-N Fibrin monomer Chemical compound CNC(=O)CNC(=O)CN BWGVNKXGVNDBDI-UHFFFAOYSA-N 0.000 description 1
- 206010020772 Hypertension Diseases 0.000 description 1
- 241001597008 Nomeidae Species 0.000 description 1
- QGMRQYFBGABWDR-UHFFFAOYSA-M Pentobarbital sodium Chemical compound [Na+].CCCC(C)C1(CC)C(=O)NC(=O)[N-]C1=O QGMRQYFBGABWDR-UHFFFAOYSA-M 0.000 description 1
- 241000700157 Rattus norvegicus Species 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- 230000002159 abnormal effect Effects 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 230000000845 anti-microbial effect Effects 0.000 description 1
- 210000000709 aorta Anatomy 0.000 description 1
- 230000023555 blood coagulation Effects 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 206010008118 cerebral infarction Diseases 0.000 description 1
- 235000019425 dextrin Nutrition 0.000 description 1
- 230000000857 drug effect Effects 0.000 description 1
- 230000002526 effect on cardiovascular system Effects 0.000 description 1
- 229950003499 fibrin Drugs 0.000 description 1
- 230000002496 gastric effect Effects 0.000 description 1
- 230000023597 hemostasis Effects 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 208000010125 myocardial infarction Diseases 0.000 description 1
- 230000007170 pathology Effects 0.000 description 1
- 229960002275 pentobarbital sodium Drugs 0.000 description 1
- 230000003285 pharmacodynamic effect Effects 0.000 description 1
- 150000003904 phospholipids Chemical class 0.000 description 1
- 230000035790 physiological processes and functions Effects 0.000 description 1
- 210000002381 plasma Anatomy 0.000 description 1
- 230000010118 platelet activation Effects 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 238000000518 rheometry Methods 0.000 description 1
- 210000004739 secretory vesicle Anatomy 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 238000012109 statistical procedure Methods 0.000 description 1
- 230000001629 suppression Effects 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 238000004879 turbidimetry Methods 0.000 description 1
Landscapes
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Abstract
The invention relates to an application of Manzamenone O in preparation of a platelet aggregation inhibitor. The application of the Manzamenone O in preparation of the platelet aggregation inhibitor disclosed by the invention is disclosed for the first time, and the Manzamenone O belongs to a brand-new skeleton type; the Manzamenone O is strong in platelet aggregation activity, has outstanding substantial characteristics, and simultaneously has a significant progress when being applied to resisting platelet aggregation.
Description
Technical field
The present invention relates to the new purposes of compound Manzamenone O, relate in particular to the application of Manzamenone O in preparing medicament for resisting platelet aggregation.
Background technology
Hematoblastic basic physiological function be stick, gathering, release and secretory granule content (as ATP, 5-hydroxy tryptamine), the platelet of quiescent condition changes states of physiologic function into and is hematoblastic activation.Phospholipid surface can be provided after platelet activation, promote the carrying out of blood coagulation, form and hold by fibrin the thrombosis that platelet forms.Therefore platelet, as a kind of visible component of blood, in the thrombosis of physiological hemostasis and pathology, plays a very important role.Clinical research shows, common cardiovascular and cerebrovascular disease is as basic in hypertension, angina pectoris myocardial infarction, cerebral infarction and cerebral hemorrhage etc. clinically, all relevant with Abnormal Blood Rheology with platelet function variation.Conventional antiplatelet drug has heavier untoward reaction at present, therefore develops novel treatment effective, that untoward reaction is little very urgent with the medicine of prevention platelet aggregation.The inventor studies by experiment, finds that Manzamenone O has the effect of antiplatelet aggregation.
The compound Manzamenone O the present invention relates to is one and within 2013, delivers (Naonobu Tanaka, et al., Manzamenone O, New Trimeric Fatty Acid Derivative from a Marine Sponge Plakortis sp.Organic Letters, 2013, 15 (10): 2518 – 2521) noval chemical compound, this compound has brand-new framework types, current purposes is found its antimicrobial (Naonobu Tanaka, et al., Manzamenone O, New Trimeric Fatty Acid Derivative from a Marine Sponge Plakortis sp.Organic Letters, 2013, 15 (10): 2518 – 2521), it is open first that the purposes of the Manzamenone O the present invention relates in preparing medicament for resisting platelet aggregation belongs to.
Summary of the invention
The invention provides the application of Manzamenone O in preparing medicament for resisting platelet aggregation.
The present invention is usingd aspirin and clopidogrel as positive drug, proof by experiment, and Manzamenone O is anticoagulant significantly, and index all significantly reduces, and maintains an equal level with positive drug.
Described compound Manzamenone O structure is as shown in formula I:
Formula I
It is open first that the purposes of the Manzamenone O the present invention relates in preparing medicament for resisting platelet aggregation belongs to, because framework types belongs to brand-new framework types, and its platelet aggregation inhibitory activity is strong, possess outstanding substantive distinguishing features, for antiplatelet aggregation, obviously there is significant progress simultaneously.
The specific embodiment
The present invention is further detailed explanation by the following examples, but protection scope of the present invention is not subject to any restriction of specific embodiment, but be limited by claim.
The preparation method of compound Manzamenone O involved in the present invention is referring to document (Naonobu Tanaka, et al., Manzamenone O, New Trimeric Fatty Acid Derivative from a Marine Sponge Plakortis sp.Organic Letters, 2013,15 (10): 2518 – 2521), prepare according to the method described above compound Manzamenone O.
Embodiment 1: the preparation of compound Manzamenone O tablet involved in the present invention:
Get 5 and digest compound Manzamenone O, add 195 grams, dextrin, mix, conventional tabletting is made 1000.
Embodiment 2: the preparation of compound Manzamenone O capsule involved in the present invention:
Get 5 and digest compound Manzamenone O, add 195 grams of starch, mix, encapsulatedly make 1000.
Below by pharmacodynamic experiment, further illustrate its pharmaceutically active.
The impact of test example 1:Manzamenone O on rat platelet aggregation function
1. animal: a clean level Sprague-Dawley rat, male, body weight 200g-250g, Nanjing Medical University's Experimental Animal Center.
2. method and result
Animal is divided into blank group (waiting capacity solvent), aspirin group (ASA at random, 50mg/kg), clopidogrel group (7mg/kg), Manzamenone O 0.625mg/kg group, Manzamenone O 1.25mg/kg group, Manzamenone O 2.5mg/kg group, every group 8, gastric infusion, 1 time/d, continuous 5d.1h after last administration, with 3% pentobarbital sodium difference anesthetized rat (30mg/kg), through ventral aorta, take a blood sample, with 3.8% liquor sodii citratis anticoagulant (blood: anticoagulant=9:1), 1000r/min, separated platelet rich plasma (PRP), remainder is again with the centrifugal 15min of 3000r/min, separated platelet poor plasma (PPP), by turbidimetry, take ADP(252umol/L) be derivant, with LBY-NJ blood pool instrument, measure platelet aggregation rate in 5min, and calculate as follows platelet aggregation inhibition rate, data represent with %, with t check between group, carry out statistical procedures, the results are shown in Table 1.
Platelet aggregation inhibition rate=(blank platelet aggregation rate %-delivery tube platelet aggregation rate %)/blank platelet aggregation rate %*100%
Known according to experimental result, each dosage group of Manzamenone O can obviously suppress platelet aggregation in body, and drug effect and positive drug aspirin and clopidogrel maintain an equal level.
Table 1Manzamenone O to hematoblastic gathering suppression ratio (, n=8)
With the comparison of blank group, * * P<0.001 * P<0.01
Conclusion: using aspirin and clopidogrel as positive drug, proof by experiment, Manzamenone O is anticoagulant significantly, maintains an equal level with positive drug, can be used for preparing medicament for resisting platelet aggregation.
Claims (1)
- The application of 1.Manzamenone O in medicament for resisting platelet aggregation, described compound Manzamenone O structure is as shown in formula I:
Formula I.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201310624207.1A CN103638015B (en) | 2013-11-28 | 2013-11-28 | Application of Manzamenone O in platelet aggregation inhibitor |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201310624207.1A CN103638015B (en) | 2013-11-28 | 2013-11-28 | Application of Manzamenone O in platelet aggregation inhibitor |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN103638015A true CN103638015A (en) | 2014-03-19 |
| CN103638015B CN103638015B (en) | 2015-07-22 |
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201310624207.1A Expired - Fee Related CN103638015B (en) | 2013-11-28 | 2013-11-28 | Application of Manzamenone O in platelet aggregation inhibitor |
Country Status (1)
| Country | Link |
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| CN (1) | CN103638015B (en) |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102872035A (en) * | 2012-10-26 | 2013-01-16 | 吴俊华 | Application of Gypensapogenin A in medicaments against platelet aggregation |
| CN102988349A (en) * | 2012-11-19 | 2013-03-27 | 何晓涛 | Application of Aphanamixoid A for preparing platelet aggregation resistant medicine |
| CN103127073A (en) * | 2012-10-25 | 2013-06-05 | 吴俊华 | Application of Eryngiolide A in anti-platelet aggregation medicines |
| CN103127153A (en) * | 2012-10-26 | 2013-06-05 | 吴俊华 | Application of Gypensapogenin B in anti-platelet aggregation medicines |
-
2013
- 2013-11-28 CN CN201310624207.1A patent/CN103638015B/en not_active Expired - Fee Related
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103127073A (en) * | 2012-10-25 | 2013-06-05 | 吴俊华 | Application of Eryngiolide A in anti-platelet aggregation medicines |
| CN102872035A (en) * | 2012-10-26 | 2013-01-16 | 吴俊华 | Application of Gypensapogenin A in medicaments against platelet aggregation |
| CN103127153A (en) * | 2012-10-26 | 2013-06-05 | 吴俊华 | Application of Gypensapogenin B in anti-platelet aggregation medicines |
| CN102988349A (en) * | 2012-11-19 | 2013-03-27 | 何晓涛 | Application of Aphanamixoid A for preparing platelet aggregation resistant medicine |
Non-Patent Citations (1)
| Title |
|---|
| NAONOBU TANAKA等: "Manzamenone O, New Trimeric Fatty Acid Derivative from a Marine Sponge Plakortis sp.", 《ORGANIC LETTERS》, vol. 15, no. 10, 7 May 2013 (2013-05-07), pages 2518 - 2521 * |
Also Published As
| Publication number | Publication date |
|---|---|
| CN103638015B (en) | 2015-07-22 |
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| Date | Code | Title | Description |
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| PB01 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| ASS | Succession or assignment of patent right |
Owner name: THE FIRST AFFILIATED HOSPITAL OF XINXIANG MEDICAL Free format text: FORMER OWNER: CHANGZHOU COLLECTION MEDICAL INSTRUMENT CO., LTD. Effective date: 20150623 |
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| C41 | Transfer of patent application or patent right or utility model | ||
| C53 | Correction of patent of invention or patent application | ||
| CB03 | Change of inventor or designer information |
Inventor after: Zhao Jianhua Inventor after: Li Qing Inventor after: Feng Hui Inventor after: Su Linlin Inventor after: Su Zhou Inventor before: Chen Jun |
|
| COR | Change of bibliographic data |
Free format text: CORRECT: INVENTOR; FROM: CHEN JUN TO: ZHAO JIANHUA LI QING FENG HUI SU LINLIN SU ZHOU |
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| TA01 | Transfer of patent application right |
Effective date of registration: 20150623 Address after: 453100 No. 88 health Road, Weihui, Henan, Xinxiang Applicant after: The First Affiliated Hospital of Xinxiang Medical University Address before: 213000 West -256-1, building 4, West Taihu international wisdom garden, Wujin Economic Development Zone, Jiangsu, Changzhou Applicant before: CHANGZHOU KELIXIN MEDICAL DEVICES CO., LTD. |
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| C14 | Grant of patent or utility model | ||
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| CF01 | Termination of patent right due to non-payment of annual fee |
Granted publication date: 20150722 Termination date: 20151128 |
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| CF01 | Termination of patent right due to non-payment of annual fee |