CN110840872A - Application of nervonic acid in preparation of anticoagulant drugs - Google Patents
Application of nervonic acid in preparation of anticoagulant drugs Download PDFInfo
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- CN110840872A CN110840872A CN201911146162.5A CN201911146162A CN110840872A CN 110840872 A CN110840872 A CN 110840872A CN 201911146162 A CN201911146162 A CN 201911146162A CN 110840872 A CN110840872 A CN 110840872A
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- nervonic acid
- rat
- viscosity
- blood
- control group
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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
- A61K31/20—Carboxylic acids, e.g. valproic acid having a carboxyl group bound to a chain of seven or more carbon atoms, e.g. stearic, palmitic, arachidic acids
- A61K31/201—Carboxylic acids, e.g. valproic acid having a carboxyl group bound to a chain of seven or more carbon atoms, e.g. stearic, palmitic, arachidic acids having one or two double bonds, e.g. oleic, linoleic acids
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/02—Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
Abstract
The invention discloses application of nervonic acid in preparing an anticoagulant drug. The rat model with qi stagnation and blood stasis is established by subcutaneous injection of adrenaline, and the rat is perfused with nervonic acid, so that the influence of the medicament on the blood coagulation time, the whole blood viscosity and the plasma viscosity of the severed rat is investigated, and the result shows that the nervonic acid can prolong the severed bleeding time and show dose dependence, and simultaneously can reduce the whole blood viscosity and the plasma viscosity of the rat, so that the nervonic acid can improve the blood rheology state of the model with qi stagnation and blood stasis, and further play the anticoagulation effect.
Description
Technical Field
The invention belongs to the field of pharmacy, and relates to a new pharmaceutical application of nervonic acid, in particular to a new application in preparing anticoagulant drugs.
Background
The Chinese pharmacopoeia 2015 edition records a traditional Chinese medicine with the effects of dissipating stagnation, relieving swelling, removing blood stasis and relieving pain, and the medicine names are Xiaojin pills, Xiaojin capsules and Xiaojin tablets, and the traditional Chinese medicine is prepared from 10 traditional Chinese medicines such as artificial musk, semen momordicae, radix aconiti agrestis, resina liquidambaris, frankincense, myrrh, trogopterus dung, angelica, earthworm, Chinese ink and the like. The formula is a classic and famous traditional Chinese medicine formula, and can be used for treating various difficult and complicated diseases such as goiter, benign prostatic hyperplasia, postherpetic neuralgia, cystic hyperplasia of breast, chronic pelvic inflammatory disease mass, nodular fasciitis and the like.
In the research process of effect substances and action mechanisms of the traditional Chinese medicine, the applicant carries out systematic research on chemical components and metabolites thereof entering an animal body after the traditional Chinese medicine is orally taken, and finally identifies a compound from the metabolites in the body by combining detection and identification means such as gas phase, liquid phase, mass spectrum, nuclear magnetic resonance and the like, wherein the compound is a known compound and is named as: tetracosenoic acid (nervonic acid), formula: c24H46O2Molecular weight: 366.62, the structural formula is as follows:
the compound is most likely to be a metabolite of the traditional Chinese medicine earthworm in vivo, and documents show that the earthworm has better pharmacological actions of resisting thrombus, resisting coagulation, dissolving thrombus, reducing fiber and the like, and the action mechanism of the earthworm is mainly to degrade fibrinogen, activate plasminogen into plasmin, promote the release of fibrinolytic activation factors, relieve the adhesion effect of platelets, prevent platelet aggregation and the like. The Xiaojin preparation also has the function of improving the blood stasis state, according to the theory of the combination of Chinese traditional medicine and western medicine, the blood stasis syndrome is mainly caused by the fluidity and viscosity change of blood, and the blood coagulation dysfunction is the main reason for the fluidity and viscosity change of the blood. Therefore, the applicant speculates that nervonic acid is closely related to the therapeutic activity of the xiaojin preparation.
Disclosure of Invention
The invention aims to provide a new application of nervonic acid in preparing anticoagulant medicaments.
The applicant establishes a rat model with qi stagnation and blood stasis by subcutaneous injection of adrenalin, and perfuses gastric nervonic acid in rats to investigate the influence of drugs on the blood coagulation time, the whole blood viscosity and the plasma viscosity of a tail-broken rat.
The nervonic acid can be independently used as an active ingredient to prepare an anticoagulant, can also be compounded with other medicines such as warfarin, heparin, aspirin and the like to prepare the anticoagulant, and can further improve the curative effect of the medicine or reduce the side effect of the medicine when being compounded with other medicines.
Pharmaceutically acceptable adjuvants can also be added during preparation of the above medicines.
Detailed Description
The present invention will now be described in further detail with reference to specific examples, which are provided for illustration of the present invention and are not intended to limit the scope of the present invention. The experimental methods used in the following examples are conventional methods unless otherwise specified, and materials, reagents and the like used therein are commercially available without otherwise specified.
The test method comprises the following steps:
50 clean-grade female SD rats with the weight of 200-250 g are taken, and are randomly divided into five groups (a normal control group, a model control group and high, medium and low dose drug groups) after being adaptively raised for one week, wherein each group comprises 10 rats. Wherein, the normal control group and the model control group are respectively gavaged with 10mL/kg CMC-Na solution (0.5%) every day, and the medicine high, medium and low dosage groups are respectively gavaged with 0.1, 0.3 and 0.9g/kg nervonic acid every day (the nervonic acid is respectively prepared with 10, 30 and 90mg/mL of CMC-Na solution with 0.5%). And (3) starting molding after continuously administering for 14 days, wherein the normal control group of rats is not molded, and the model control group and the drug group are both prepared into the acute blood stasis animal model by subcutaneous injection of epinephrine, and the specific molding method comprises the following steps: the injection solution (1.6mg/kg) of epinephrine hydrochloride is injected subcutaneously into the inner thigh of a rat in two times, wherein the two times are separated by 4 hours, the rat is placed in an ice water bath for 5min after each injection, and the rat is fasted without water supply after the last injection. After fasting for 12 hours, the rat is fixed in a cylinder, the tail end of the rat tail is reduced by 0.5cm, timing is started until bleeding is stopped, bleeding time is recorded, then the rat is anesthetized by 20% urethane intraperitoneal injection, 6mL of blood is taken from the carotid artery and added into a heparin tube, after vortex, an automatic blood viscometer is used for measuring the whole blood viscosity at different shear rates, 1mL of anticoagulation blood is taken, centrifugation is carried out for 15min at 3000r/min, and supernatant plasma is taken and the plasma viscosity is measured by a trace plasma tester.
And (3) test results:
1. the bleeding time of broken tail of each group of rats is respectively as follows: normal control group (23 + -11) s, model control group (16 + -5) s, drug low dose group (21 + -9) s, drug medium dose group (26 + -9) s, and drug high dose group (33 + -9) s. Compared with a normal control group, the bleeding time of the model control group is obviously shortened (P is less than 0.05), which indicates that the acute blood stasis animal model is successfully molded; nervonic acid can prolong the bleeding time of broken tail and is dose-dependent, which shows that the nervonic acid has anticoagulant effect, and compared with a model control group, the bleeding time of a medium-high drug dose group is remarkably prolonged (P is less than 0.05).
2. The influence of nervonic acid on the whole blood viscosity and the plasma viscosity of the rats is shown in table 1, and the results show that the whole blood viscosity of the rats in the model control group is obviously higher than that of the rats in the normal control group (P is less than 0.05), and although the difference between the whole blood viscosity of the rats in the high cut group has no statistical significance, the absolute value of the model control group is higher than that of the rats in the normal control group, which indicates that the whole blood viscosity is improved by injection of adrenergic. The whole blood viscosity of the rats in the nervonic acid drug group is obviously lower than that of the rats in the model control group, and the rats show a dose-dependent trend. In addition, the plasma viscosity of rats in the nervonic acid drug group is remarkably reduced compared with that in the model control group, wherein the medium and high dose groups have a remarkable difference (P < 0.05). The experiments show that the nervonic acid can obviously reduce the whole blood viscosity and the plasma viscosity of the acute blood stasis rat, thereby having the anticoagulation effect.
TABLE 1 Effect of nervonic acid on Whole blood viscosity in rats
Compared with the normal control group,#p is less than 0.05; the comparison of the model with the control group,＊P＜0.05。
Claims (4)
1. use of nervonic acid in preparing anticoagulant medicine is provided.
2. An anticoagulant medicine contains nervonic acid as active ingredient.
3. The anticoagulant medication of claim 2, wherein: also contains pharmaceutically acceptable auxiliary materials.
4. The anticoagulant medication of claim 2, wherein: the medicament is an oral medicament.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201911146162.5A CN110840872B (en) | 2019-11-21 | 2019-11-21 | Application of nervonic acid in preparation of anticoagulant drugs |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201911146162.5A CN110840872B (en) | 2019-11-21 | 2019-11-21 | Application of nervonic acid in preparation of anticoagulant drugs |
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| Publication Number | Publication Date |
|---|---|
| CN110840872A true CN110840872A (en) | 2020-02-28 |
| CN110840872B CN110840872B (en) | 2020-11-20 |
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| Application Number | Title | Priority Date | Filing Date |
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| CN201911146162.5A Active CN110840872B (en) | 2019-11-21 | 2019-11-21 | Application of nervonic acid in preparation of anticoagulant drugs |
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Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2002076402A2 (en) * | 2001-03-23 | 2002-10-03 | Protarga, Inc. | Fatty amine drug conjugates |
| CN101690564A (en) * | 2009-09-30 | 2010-04-07 | 武兴战 | Natto product capable of dissolving thrombus |
| CN103637185A (en) * | 2013-11-18 | 2014-03-19 | 南京圣诺生物科技实业有限公司 | Nervonic acid composition |
| CN106581109A (en) * | 2017-02-28 | 2017-04-26 | 王沛 | Cerebral thrombosis treating pharmaceutical composition |
-
2019
- 2019-11-21 CN CN201911146162.5A patent/CN110840872B/en active Active
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2002076402A2 (en) * | 2001-03-23 | 2002-10-03 | Protarga, Inc. | Fatty amine drug conjugates |
| CN101690564A (en) * | 2009-09-30 | 2010-04-07 | 武兴战 | Natto product capable of dissolving thrombus |
| CN103637185A (en) * | 2013-11-18 | 2014-03-19 | 南京圣诺生物科技实业有限公司 | Nervonic acid composition |
| CN106581109A (en) * | 2017-02-28 | 2017-04-26 | 王沛 | Cerebral thrombosis treating pharmaceutical composition |
Non-Patent Citations (1)
| Title |
|---|
| 王性炎等: "神经酸研究现状及应用前景", 《中国油脂》 * |
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| CN110840872B (en) | 2020-11-20 |
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