CN106620707A - Pharmaceutical composition for preventing and treating myocardial ischemia as well as preparation and application thereof - Google Patents
Pharmaceutical composition for preventing and treating myocardial ischemia as well as preparation and application thereof Download PDFInfo
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- CN106620707A CN106620707A CN201710151839.9A CN201710151839A CN106620707A CN 106620707 A CN106620707 A CN 106620707A CN 201710151839 A CN201710151839 A CN 201710151839A CN 106620707 A CN106620707 A CN 106620707A
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- pharmaceutical composition
- myocardial ischemia
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- anticoagulation
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
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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
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
- A61K31/19—Carboxylic acids, e.g. valproic acid
- A61K31/192—Carboxylic acids, e.g. valproic acid having aromatic groups, e.g. sulindac, 2-aryl-propionic acids, ethacrynic acid
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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
- A61K31/365—Lactones
- A61K31/366—Lactones having six-membered rings, e.g. delta-lactones
- A61K31/37—Coumarins, e.g. psoralen
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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
- A61K31/66—Phosphorus compounds
- A61K31/661—Phosphorus acids or esters thereof not having P—C bonds, e.g. fosfosal, dichlorvos, malathion or mevinphos
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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
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
- A61K9/4841—Filling excipients; Inactive ingredients
- A61K9/4866—Organic macromolecular compounds
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- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Abstract
The invention relates to a pharmaceutical composition for preventing and treating myocardial ischemia as well as a preparation and an application thereof. The pharmaceutical composition employs sphingosine-1-phosphate, naproxen and an anticoagulant medicine as medicinal active components, wherein the anticoagulant medicine is selected from heparin, dicoumarol, acetonyl benzyl hydroxycoumarin, aspirin and the like, and preferably dicoumarol. Synergistically interacted multi-path between medicinal active components of the pharmaceutical composition perform effects for prevention and treatment of myocardial ischemia, and improve myocardial ischemic electrocardiogram change and anticoagulation. The pharmaceutical composition can be taken orally or applied parenterally, in order to effectively prevent and treat myocardial ischemia, prevent and alleviate angina pectoris, myocardial infarction or ischemic cardiomyopathy, and the like.
Description
Technical field
The invention belongs to drug world, in particular it relates to a kind of pharmaceutical composition of prevention and treatment myocardial ischemia and its
Preparation method and purposes.
Background technology
Modern society is due to the quickening of rhythm of life, excessive consumption of alcohol, nutrition intake is superfluous, lack necessary motion and environment
Pollution etc., result in cardiovascular and cerebrovascular disease becomes one of the commonly encountered diseases for threatening human health, with high prevalence, high disability rate and
The characteristics of high mortality, according to statistics, current cardiovascular and cerebrovascular disease has become the first cause of whole world human death.Myocardial ischemia
One of common disease for cardiovascular and cerebrovascular disease, generally refers to result in the confession of heart due to the reduction of the hemoperfusion of heart
Oxygen is reduced, and energy metabolism of myocardial is not normal, so as to support that the pathological state of normal heart action, clinical symptoms mainly include labor
There is uncomfortable in chest, cardiopalmus, shortness of breath etc. during tired or psychentonia, there is the risk that angina pectoriss, myocardial infarction and sudden death occur.Due to life
The raising of level, myocardial ischemia has no longer only been the healthy threat of old people, starts the trend for presenting rejuvenation,
Also the related symptoms for myocardial ischemia occur are had started in the crowd of less than 30 years old, so as to seriously threaten the healthy of the mankind.
Myocardial ischemia be because the reduction of the hemoperfusion of heart is induced, therefore, at present, be directed to controlling for myocardial ischemia
Treatment focuses primarily upon Drug therapy and surgical operation therapy, and its drug treatment is concentrated on and uses the expansion hat such as nitrate esters medicine
Shape tremulous pulse, increases blood supply of cardiac muscle oxygen supply；Suppress the receipts of cardiac muscle using beta-blockers decreased heart rate or using calcium ion antagonist
Contracting etc., so as to reduce the oxygen consumption of cardiac muscle；Using antiplatelet drug, statinses, thrombolytic drug etc., prevent or dissolve blood
Bolt etc..Said medicine treatment is often only capable of playing the effect of relief of symptoms, and side effect is larger, or even can also aggravate corresponding disease
Shape, therefore, therapeutic effect is unsatisfactory.
S1P (Sphingosine-1-phosphate, abbreviation S1P) be sphingomyelins metabolism intermediate product it
One, with important physiological function, its receptor wide expression in endotheliocyte, vascular smooth muscle cell and myocardial cell etc., because
This, S1P can extensively play the effect such as blood vessel endothelium protection, protection of Ischemic/reperfusion, can also reduce ventricular muscles action
Current potential amplitude, over reach potential duration, increase myocardial contraction, such that it is able to play Ischemic/reperfusion protection work
With while, be conducive to correct myocardial ischemia when cardiac muscle abnormal operating state.
The present invention is to be studied for S1P, is devoted to developing a kind of myocardial ischemia prevention and treatment
The more preferable pharmaceutical composition of effect.
The content of the invention
It is an object of the present invention to provide a kind of medicine of the prevention and treatment myocardial ischemia comprising S1P
Compositionss, described pharmaceutical composition is with S1P, naproxen and anticoagulation as active component.
The mass ratio of S1P, naproxen and anticoagulation is 5-10: 5-10: 1- wherein in described pharmaceutical composition
5, preferably 6-8: 6-8: 2-4, more preferably 6: 6: 2,7: 7: 2,8: 8: 2,6: 6: 3,7: 7: 3,8：8∶3、6∶6∶4、7∶7∶
4、8∶8∶4。
The anticoagulation is selected from：Heparin, warfarin, dicoumarol etc..
The preferred anticoagulation is dicoumarol.
The pharmaceutical composition of present invention prevention and treatment myocardial ischemia can add pharmaceutically acceptable adjuvant and be prepared into
It is easy to the pharmaceutical dosage form of Clinical practice, the pharmaceutical dosage form includes combination of oral medication or gastrointestinal drug compositionss, described
Combination of oral medication is preferably tablet or capsule, and the parenteral pharmaceutical composition is preferably injection or freeze-dried powder
Agent.
In the pharmaceutical composition of the present invention for preparing, the S1P, naproxen as active constituents of medicine
With the 0.1-10% (weight) that the content of anticoagulation is pharmaceutical composition gross weight.
In further preferred technical scheme, the pharmaceutical composition of present invention prevention and treatment myocardial ischemia is capsule
Agent, the capsule includes：S1P, naproxen and anticoagulation and pharmaceutically acceptable adjuvant, it is described pharmaceutically
Acceptable adjuvant includes：Filler, lubricant and gelatine capsule shell, the filler is selected from starch, dextrin, Lactose or crystallite
Cellulose, the lubricant is selected from：Pulvis Talci, magnesium stearate or micropowder silica gel.
In preferred technical scheme, the capsule of present invention prevention and treatment myocardial ischemia has consisting of：
4 parts of S1P；
4 parts of naproxen；
2 parts of dicoumarol；
89 parts of Microcrystalline Cellulose；
1 part of magnesium stearate.
Another object of the present invention is to provide a kind of preparation method of the capsule of prevention and treatment myocardial ischemia, the system
Preparation Method comprises the steps：
A) S1P, naproxen and anticoagulation and filling beyond weighing lubricant, gelatine capsule shell by proportioning
Crush after agent mix homogeneously, cross 50-100 mesh sieves, obtain mixed powder, it is standby；
B) add to be stirred after lubricant in the mixed powder prepared in step a and must fill powder, it is standby；
C) powder filling and gelatine capsule shell will be filled obtained in step b, is obtained final product.
It is also another object of the present invention to provide S1P, naproxen and anticoagulation are preparing the prevention and treatment heart
Purposes in the pharmaceutical composition of myocardial ischemia, the myocardial ischemia is selected from angina pectoriss, myocardial infarction or ischemic cardiomyopathy.
Naproxen：Also known as naproxen, Naproxen, the effect with antipyretic, analgesia, antiinflammatory, for rheumatoid
The treatment of arthritis, ankylosing spondylitiss, dysmenorrhea etc., it is analgesic effect persistent period length, safe.
Anticoagulation：Refer to the medicine for preventing coagulation process effect, can be used to preventing or treat thrombosis, prevention of stroke or
Other thrombosis relevant diseases, including：Heparin, Coumarinses anticoagulation, antiplatelet drug etc..
Beneficial effect
Active component S1P in the pharmaceutical composition of present invention prevention and treatment myocardial ischemia, naproxen and anti-
Solidifying medicine synergism, the effect of the performance prevention and treatment myocardial ischemia of multi-path, therapeutic effect is clear and definite and safe.
Naproxen with antipyretic, analgesia, antiinflammatory action is used for first the present invention prevention and treatment of myocardial ischemia, naphthalene
Multi-path plays the prevention and treatment work of myocardial ischemia after general life and S1P and anticoagulation, such as dicoumarol combination
With, and Synergistic, the prevention and treatment definite effect of myocardial ischemia, and it is safe, can be widely used for all kinds of myocardial ischemia
And its prevention of relevant disease and treatment.
Specific embodiment
The present invention is described below in more detail to contribute to the understanding of the present invention.
It should be appreciated that the term for using in the specification and in the claims or word be not construed as have
In dictionary limit implication, and be interpreted as on the basis of following principle have and its implication one in the context of the present invention
The implication of cause：The concept of term can suitably by inventor in order to the present invention best illustration and limit.
Effect example 1：Impact of the pharmaceutical composition of the present invention to rat
(1) rat myocardial cell primary culture method：The SD neonatal rats 25 in raw 24h are taken out, after heart all takes out, is picked
Except the blood clotting and fibrous tissue of heart periphery, Digestive system (0.125% pancreatin+0.05%II Collagenase Types) digestion, cell is collected,
It is filtered to remove and does not digest tissue, in being inoculated in culture bottle, culture in cell culture incubator (37 DEG C, 95%O2+5%CO2) is put, with difference
Fast adherent method removes fibrocyte, purification myocardial cell.After 2h, suction out not yet adherent cell suspension and blow even, adjustment density to 1
× 10-6 is implanted in 24 orifice plates (per μ l of hole 500), is uniformly distributed cell, adds Brdu to 0.1mmol/L, 24h to change liquid once,
Change liquid once per 3-4d later.Periodically under inverted microscope observation of cell growth situation, after culture 48h, be grouped at random into
Row experiment.
By cell with 1 × 106The density of individual/ml is inoculated in 24 orifice plates, per the μ l of hole 500.37 DEG C, 5%CO2 saturated humidities
Under the conditions of cultivate.After primary myocardial cell culture 72h, Normal group and model group are normally trained with 500 μ l DMEM culture fluid
Support, each administration group adds the DMEM culture fluid containing 10% medicinal liquid, after incubation 6h, with ice-cold PBS flushings 2 times, model group and administration
Group adds 500 μ l Jing 95%N per hole2- 5%O2The Tyrode liquid of saturation, is then put into culture plate in one hermetic container, continues
Pass to mixed gas (95%N2- 5%O2) hermetic container after 30min, incubator anoxia 12h is put into, simulate in body ischemia model.Just
Often group is cleaned and add after old culture medium Tyrode liquid 500 μ l, CO containing 10g/L glucoses212h is cultivated in incubator.
The final concentration of μ l of 0.5mg/ml MTT serum-free DMEM culture fluid 500 are added to cultivate 4h per hole, then incline supernatant
Liquid, adds the DMSO of 500 μ l, shakes 10min, and with full-automatic microplate reader the absorbance (OD570nm) at 570nm is determined, and uses
In quantitative cell survival rate.
Culture plate after process is drawn into 200 μ l culture supernatants per hole, is illustrated according to LDH detection kit, detect LDH
Activity.
(2) concrete outcome is as follows：
Impact of each single medicinal material to the rat myocardial cell of Anoxia, is by Radix Salviae Miltiorrhizae alcohol extraction and water extraction by Radix Salviae Miltiorrhizae extract
Extractum mixing is obtained final product, and Radix Et Caulis Acanthopanacis Senticosi and Radix Notoginseng extract respectively the extract for obtaining final product two taste medicines, and the preparation method of each extract is with enforcement
Example 1.
Cell survival rate (MTT) and LDH activity result are as follows：
| Packet | LDH(U/L) | Cytoactive (%) |
| Matched group | 16.3±3.7 | 100 |
| Model group | 136.8±11.9## | 50.6±2.7## |
| Administration group 1 | 83.6±8.4** | 66.9±3.6** |
| Administration group 2 | 97.5±7.3** | 61.3±3.4** |
| Administration group 3 | 112.1±10.6 | 52.2±2.9 |
| Administration group 4 | 91.5±9.4** | 64.7±4.1** |
| Administration group 5 | 104.7±8.8* | 58.1±3.7* |
| Administration group 6 | 57.4±6.3**$$ | 84.6±3.9**$$ |
| Administration group 7 | 73.6±6.9** | 73.7±4.3** |
| Administration group 8 | 68.7±5.8** | 75.2±3.8** |
| Administration group 9 | 88.4±6.1** | 65.8±3.3** |
| Administration group 10 | 93.8±7.4** | 61.2±3.7** |
* represents that Jing Oneway-ANOVA are checked compared with model group, P ＜ 0.01；$$Represent Jing Oneway-ANOVA inspections
Test compared with other administration groups, P ＜ 0.01.
Each administration group is consisted of：
Effect example 2：Pharmaceutical composition of the present invention causes the Electrocardiographic impact of Acute Myocardial Ischemia Rats on pituitrin
1.1 Experimental agents
(1) pharmaceutical composition of the present invention：S1P, naproxen and dicoumarol are weighed according to 8: 8: 4 ratio,
Add pure water after mixing and be configured to the high dose, middle dosage and low dose group suspension that content is 20%, 10%, 5%；
(2) S1P group：Weigh addition pure water after S1P and be configured to the suspension that content is 20%
Liquid；
(3) naproxen group：Weigh addition pure water after naproxen and be configured to the suspension that content is 20%；
(4) dicoumarol group：Weigh addition pure water after dicoumarol and be configured to the suspension that content is 20%.
1.2 experimental technique
The SD rats 70 of screening normal ECG, male and female half and half are randomly divided into 7 groups, 10 per group, specially：It is blank
Group, high dose group of the present invention, middle dose group of the present invention, low dose group of the present invention, S1P group, naproxen group and double perfume (or spice)
Legumin group, is administered once a day per group, gavage relative medicine 3mL, wherein blank group gavage equal-volume pure water.Gastric infusion 10
My god, last dose sublingual vein injection of pituitrin 1U/Kg after 1 hour records Rat Ecg, measurement injection lobus posterior hypophyseoss
Rat ST sections, the change of T ripples in plain 30 seconds, calculate ST sections change suppression ratio and T ripples change suppression ratio, and using slide method blood coagulation is measured
Time, Coagulative inhibitors rate is calculated, specific experiment the results are shown in Table 1, table 2.Wherein
ST sections change suppression ratio=(blank group-experimental group)/blank group；
T ripples change suppression ratio=(blank group-experimental group)/blank group；
Coagulative inhibitors rate=(experimental group-blank group)/blank group.
1.3 result of the test
The experimental result of table 1 shows that blank group rat ST sections, T ripples after injection of pituitrin are substantially raised, from
And show that this experimental model is successfully constructed.The experimental result of each administration group then shows and individually gives S1P, Nabumetone
After raw and dicoumarol, only S1P shows improves the effect that pituitrin causes ECG Change, injects naphthalene
Not showing after general life and dicoumarol improves the effect that pituitrin causes ECG Change, so as to indicate exclusive use
It has the effect for improving acute myocardial ischemia ECG Change when naproxen and dicoumarol.And the medicine of the present invention
The high, medium and low dosage group of compositionss then shows the effect for significantly improving acute myocardial ischemia ECG Change, wherein low
The corresponding effect of dosage group is roughly the same with S1P group, and the dosage of pharmaceutical composition low dose group of the present invention is only
It is 1/4 with S1P group, so as to indicate pharmaceutical composition of the present invention, to improve acute myocardial ischemia Electrocardiographic
The effect of change not only relies upon S1P, and with S1P group dosage identical medicine of the present invention
The ST sections change suppression ratio of high dose group, T ripples change suppression ratio are the twice of S1P group, and the experimental result is more
Sufficiently show after S1P, naproxen are combined with dicoumarol in pharmaceutical composition of the present invention that collaboration has been played to change
The effect of kind acute myocardial ischemia Rat Ecg change.
Experimental agents cause the Electrocardiographic impact of Acute Myocardial Ischemia Rats on pituitrin
Note：Compare with blank group：* P ＜ 0.05, * * P ＜ 0.01, * * * P ＜ 0.001.
Impact of the Experimental agents to rat clotting time
Note：Compare with blank group：* P ＜ 0.05, * * P ＜ 0.01, * * * P ＜ 0.001.
The experimental result of table 2 shows that dicoumarol has blood coagulation resisting function, and S1P does not show with naproxen
Anticoagulant effect is shown, but pharmaceutical composition of the present invention comprising S1P, naproxen and dicoumarol then shows
Clearly more powerful blood coagulation resisting function, wherein there is pharmaceutical composition low dose group of the present invention the anticoagulation similar with dicoumarol to make
With, but its dosage is only the 1/4 of dicoumarol group, and the Coagulative inhibitors rate of pharmaceutical composition high dose group of the present invention is substantially high
In dicoumarol group, so as to table also understands that pharmaceutical composition of the present invention also has the anticoagulant effect of collaboration.
The capsule of embodiment 1, prevention and treatment myocardial ischemia
The capsule has consisting of：
4 parts of S1P；
4 parts of naproxen；
2 parts of dicoumarol；
89 parts of Microcrystalline Cellulose；
1 part of magnesium stearate.
Prepare in accordance with the following steps：
A) S1P, naproxen and anticoagulation and filling beyond weighing lubricant, gelatine capsule shell by proportioning
Crush after agent mix homogeneously, cross 100 mesh sieves, obtain mixed powder, it is standby；
B) add to be stirred after lubricant in the mixed powder prepared in step a and must fill powder, it is standby；
C) powder filling and gelatine capsule shell will be filled obtained in step b, is obtained final product.
Claims (10)
1. a kind of pharmaceutical composition for preventing and treating myocardial ischemia, it is characterised in that with S1P, naproxen
With anticoagulation as active constituents of medicine.
2. it is according to claim 1 prevention and treatment myocardial ischemia pharmaceutical composition, it is characterised in that the 1- phosphoric acid
The mass ratio of sphingol, naproxen and anticoagulation be 5-10: 5-10: 1-5, preferably 6-8: 6-8: 2-4, more preferably 6: 6:
2、7∶7∶2、8∶8∶2、6∶6∶3、7∶7∶3、8∶8∶3、6∶6∶4、7∶7∶4、8∶8∶4。
3. it is according to claim 1 prevention and treatment myocardial ischemia pharmaceutical composition, it is characterised in that the anticoagulation
It is selected from：Heparin, warfarin, dicoumarol.
4. it is according to claim 3 prevention and treatment myocardial ischemia pharmaceutical composition, it is characterised in that the anticoagulation
For dicoumarol.
5. according to any one of claim 1-4 prevention and treatment myocardial ischemia pharmaceutical composition, it is characterised in that institute
The content for stating S1P, naproxen and anticoagulation accounts for the 0.1-10% of described pharmaceutical composition gross weight.
6. according to any one of claim 1-4 prevention and treatment myocardial ischemia pharmaceutical composition, it is characterised in that institute
It is combination of oral medication or parenteral pharmaceutical composition to state pharmaceutical composition, and the combination of oral medication is preferably tablet
Or capsule, the parenteral pharmaceutical composition is preferably injection or lyophilized injectable powder.
7. it is according to claim 6 prevention and treatment myocardial ischemia pharmaceutical composition, it is characterised in that the capsule
Composition include：S1P, naproxen and anticoagulation and pharmaceutically acceptable adjuvant, it is described pharmaceutically acceptable
Adjuvant includes：Filler, lubricant and gelatine capsule shell, the filler is selected from starch, dextrin, Lactose or Microcrystalline Cellulose,
The lubricant is selected from：Pulvis Talci, magnesium stearate or micropowder silica gel.
8. it is a kind of prepare described in claim 7 prevention and treatment myocardial ischemia pharmaceutical composition method, it is characterised in that
The preparation method following steps：
A) S1P, naproxen and anticoagulation and filler beyond weighing lubricant, gelatine capsule shell by proportioning is mixed
Uniform rear crushing is closed, 50-100 mesh sieves are crossed, mixed powder is obtained, it is standby；
B) add to be stirred after lubricant in the mixed powder prepared in step a and must fill powder, it is standby；
C) powder filling and gelatine capsule shell will be filled obtained in step b, is obtained final product.
The purposes of 9.1- phosphoric acid sphingols, naproxen and anticoagulation in the pharmaceutical composition for preparing prevention or treating myocardial ischemia.
10. purposes according to claim 9, it is characterised in that the myocardial ischemia is selected from angina pectoriss, myocardial infarction or lacks
Courageous and upright cardiomyopathy.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201710151839.9A CN106620707B (en) | 2017-03-14 | 2017-03-14 | A kind of pharmaceutical composition and its preparation method and application preventing and treating myocardial ischemia |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201710151839.9A CN106620707B (en) | 2017-03-14 | 2017-03-14 | A kind of pharmaceutical composition and its preparation method and application preventing and treating myocardial ischemia |
Publications (2)
| Publication Number | Publication Date |
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| CN106620707A true CN106620707A (en) | 2017-05-10 |
| CN106620707B CN106620707B (en) | 2019-06-07 |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN112933081A (en) * | 2021-03-26 | 2021-06-11 | 河北医科大学 | Application of dicoumarol in preparation of anti-epilepsy and analgesic drugs |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2011060944A2 (en) * | 2009-11-20 | 2011-05-26 | Gp Pharm, S.A. | Active pharmaceutical ingredient capsules and polyunsaturated fatty acid esters |
| CN105726576A (en) * | 2016-02-04 | 2016-07-06 | 刘玉财 | Tablet used for treating angina in slow-release stage and preparation method thereof |
-
2017
- 2017-03-14 CN CN201710151839.9A patent/CN106620707B/en active Active
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2011060944A2 (en) * | 2009-11-20 | 2011-05-26 | Gp Pharm, S.A. | Active pharmaceutical ingredient capsules and polyunsaturated fatty acid esters |
| CN105726576A (en) * | 2016-02-04 | 2016-07-06 | 刘玉财 | Tablet used for treating angina in slow-release stage and preparation method thereof |
Non-Patent Citations (2)
| Title |
|---|
| 景小东，等: "1-磷酸鞘氨醇在心血管***中作用的研究进展", 《医学综述》 * |
| 鲁艳菊，等: "S1P/S1PR2的心血管调节作用及其信号通路", 《中国心血管杂志》 * |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN112933081A (en) * | 2021-03-26 | 2021-06-11 | 河北医科大学 | Application of dicoumarol in preparation of anti-epilepsy and analgesic drugs |
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| CN106620707B (en) | 2019-06-07 |
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