阅读说明：本技术 一种防治脑梗塞的药物组合物及其用途 (Pharmaceutical composition for preventing and treating cerebral infarction and application thereof ) 是由 李丛言 孙瑞雪 孙光涛 于 2020-06-17 设计创作，主要内容包括：本发明涉及一种防治脑梗塞的药物组合物及其用途,其包含白术内酯II、洛伐他汀和B族维生素作为药物活性成分,三种药物活性成分之间存在协同增效的作用。所述药物组合物能够显著降低脑梗塞面积,改善神经功能系统,产生明显优于单药使用的治疗效果,防治脑梗塞的效果明显。(The invention relates to a pharmaceutical composition for preventing and treating cerebral infarction and application thereof, wherein the pharmaceutical composition comprises atractylenolide II, lovastatin and B vitamins as pharmaceutical active ingredients, and the three pharmaceutical active ingredients have a synergistic effect. The pharmaceutical composition can obviously reduce the area of cerebral infarction, improve the nervous system, produce the treatment effect obviously superior to that of single medicine use, and has obvious effect of preventing and treating cerebral infarction.)

1. The pharmaceutical composition for preventing and treating cerebral infarction is characterized in that the active ingredients of the pharmaceutical composition comprise atractylenolide II, lovastatin and B vitamins.

2. The pharmaceutical composition according to claim 1, characterized in that the mass ratio of atractylenolide II, lovastatin and B vitamins is 1-8:3-20:0.5-3, preferably 2-6:5-10: 0.5-2.

3. The pharmaceutical composition according to claim 2, wherein the mass ratio of atractylenolide II, lovastatin and B vitamins is 5:10:1 or 5:5: 0.5.

4. The pharmaceutical composition according to claim 1, wherein the sum of the masses of atractylenolide II, lovastatin and B vitamins represents 1-15% (by weight), preferably 3-12% (by weight), more preferably 4-10% (by weight) of the total mass of the pharmaceutical composition.

5. The pharmaceutical composition according to claim 4, wherein the total mass of atractylenolide II, lovastatin and B vitamins is 2%, 4%, 5%, 7% of the total mass of the pharmaceutical composition.

6. The pharmaceutical composition of claim 1, wherein the B vitamins are selected from one or more of vitamin B1, vitamin B2, vitamin B6, vitamin B12, niacin, pantothenic acid, folic acid, and biotin.

7. Pharmaceutical composition according to claim 6, characterized in that the B vitamins are preferably vitamin B1: folic acid: biotin is a 1:1:2 mixture.

8. The pharmaceutical composition according to any one of claims 1 to 7, wherein the pharmaceutical composition is in a dosage form selected from the group consisting of an oral preparation and an intravenous preparation.

9. The pharmaceutical composition of claim 8, wherein the dosage form is selected from the group consisting of a tablet, a capsule, an intravenous solution, and an intravenous infusion solution.

10. Use of the pharmaceutical composition according to any one of claims 1 to 9 for the preparation of a medicament for preventing and treating cerebral infarction.

Technical Field

The invention belongs to the technical field of medicines, and particularly relates to a pharmaceutical composition for preventing and treating cerebral infarction and application thereof.

Background

Cerebral infarction, also known as cerebral infarction and ischemic stroke, refers to ischemic necrosis or softening of limited brain tissue caused by cerebral blood supply disorder, ischemia and hypoxia, is a common clinical cardiovascular and cerebrovascular disease and nervous system disease, has the characteristics of high morbidity, high mortality and the like, and becomes one of the major challenges of public health. Cerebral infarction belongs to sudden brain diseases, the current incidence trend is younger, the cerebral infarction is likely to occur in any age group, and the degree of cerebral necrosis is different due to different thrombus positions and sizes. Cerebral infarction frequently occurs in a more acute way, and has no prodromal symptoms, the focal nerve sign reaches the peak within minutes to hours, and the cerebral infarction is caused in a large area by complete stroke, clear consciousness or mild consciousness disturbance, and main embolism of internal carotid artery or middle cerebral artery, so that severe encephaledema, intracranial pressure increase, even cerebral hernia and coma can occur.

Currently, the following damage mechanisms are mainly used for cerebral infarction: firstly, nerve excitotoxicity, excessive glutamic acid causes intracellular calcium release to cause nerve cell apoptosis; secondly, a large amount of extracellular calcium ions enter cells to cause calcium overload, so that nerve cells are subjected to apoptosis; thirdly, a large amount of oxidative free radicals are generated to cause cascade nervous excitotoxicity, inflammatory reaction and the like, thereby causing cell apoptosis; and fourthly, inflammatory reaction, in the process of cerebral infarction, inflammatory cells in brain tissues are activated (for example, leukocytes), a large amount of inflammatory factors (for example, IL-1 or TNF-alpha) are released, and nerve cells are directly damaged.

The clinical treatment principle for cerebral infarction mainly aims at improving blood circulation of cerebral ischemic regions as early as possible, promoting nerve function recovery and the like. The clinical drugs mainly comprise thrombolytic drugs during the onset of diseases, for example, recombinant tissue plasminogen activator is one of the well-known effective drugs, but the clinical drugs have many side effects during the use process, and the treatment time window is limited, so that reperfusion injury is easily caused if the clinical drugs are used in the wrong time window, thereby causing the death of patients. With the progress of the research on the mechanism of cerebral infarction, neuroprotective agents or nerve regeneration agents have been tried to be applied to the treatment of cerebral infarction, for example, edaravone, which achieves the protective effect of cerebral nerve cells by an antioxidant mechanism, and lovastatin, which achieves the neuroprotective effect by anti-inflammatory and antioxidant effects, while nerve growth factors (e.g., NGF) have been tried to achieve the effect of promoting nerve regeneration at the injured site of cerebral infarction by injection administration.

However, the above drugs are often used alone clinically, and the effects of relieving symptoms, shortening the course of disease and the like are limited. Therefore, there is a need for development of a combination preparation and improvement of the effect of preventing and treating cerebral infarction.

Disclosure of Invention

In order to overcome the problems and the defects of the existing cerebral infarction prevention and treatment, the invention provides the pharmaceutical composition for preventing and treating the cerebral infarction, the pharmaceutical active ingredients of the pharmaceutical composition have a synergistic interaction effect, the cerebral infarction is effectively prevented and treated, the incidence rate of nerve function damage and the like caused by the cerebral infarction is reduced, and the treatment requirements of patients are better met.

The technical scheme of the invention is as follows:

a pharmaceutical composition for preventing and treating cerebral infarction contains Atractylodes macrocephala lactone II, lovastatin and B vitamins as effective components.

In one embodiment, the mass ratio of atractylenolide II, lovastatin and B vitamins is 1-8:3-20:0.5-3, preferably 2-6:5-10:0.5-2, in particular may be 5:10:1 or 5:5: 0.5.

In a preferred embodiment, the sum of the masses of the three active ingredients is between 1 and 15% by weight of the total mass of the pharmaceutical composition, the above-mentioned content being preferably between 3 and 12% by weight, more preferably between 4 and 10% by weight, and in particular it may be 2%, 4%, 5%, 7%.

In one embodiment, the B vitamins are selected from one or more of vitamin B1, vitamin B2, vitamin B6, vitamin B12, niacin, pantothenic acid, folic acid, biotin.

In one embodiment, the B vitamins are preferably vitamin B1: folic acid: biotin is a 1:1:2 mixture.

In one embodiment, the dosage form of the medicament is selected from oral preparations and intravenous preparations, preferably tablets, capsules, intravenous solutions or solutions for intravenous infusion.

In order to make the above dosage forms possible, pharmaceutically acceptable excipients, such as: bulking agent, disintegrating agent, lubricant, suspending agent, binder, sweetener, correctant, antiseptic, solubilizer, cosolvent, antioxidant, pH regulator, isotonic regulator, emulsifier, water for injection, non-aqueous solvent, matrix, etc. The filler comprises starch, pregelatinized starch, lactose, mannitol, chitin, microcrystalline cellulose, sucrose, etc.; the disintegrating agent comprises starch, pregelatinized starch, microcrystalline cellulose, sodium carboxymethyl starch, cross-linked polyvinylpyrrolidone, low-substituted hydroxypropyl cellulose, cross-linked sodium carboxymethyl cellulose, etc.; lubricants include magnesium stearate, sodium lauryl sulfate, talc, silica, and the like; the suspending agent comprises polyvinylpyrrolidone, microcrystalline cellulose, sucrose, agar, hydroxypropyl methylcellulose, etc.; the adhesive comprises starch slurry, polyvinylpyrrolidone, hydroxypropyl methylcellulose and the like; the sweetener comprises saccharin sodium, aspartame, sucrose, sodium cyclamate, glycyrrhetinic acid, etc.; the flavoring agent comprises sweetener and various essences; the antiseptic includes nipagin, benzoic acid, sodium benzoate, sorbic acid and its salts, benzalkonium bromide, chloroacetidine acetate, eucalyptus oil, etc.; solubilizers include nonionic tweens, such as tween 80, tween 60, and the like; the cosolvent comprises organic acid and sodium salt thereof, amino acid, vitamins and the like; the antioxidant comprises sodium sulfite, sodium bisulfite, propyl gallate, glutathione, sodium thiosulfate, thiourea, thioglycolic acid, sodium metabisulfite, potassium metabisulfite, vitamin E, etc.; the pH regulator comprises hydrochloric acid, sulfuric acid, lactic acid, malic acid, acetic acid, citric acid, sodium hydroxide, sodium carbonate, sodium bicarbonate, disodium hydrogen phosphate, sodium dihydrogen phosphate, etc.; the isotonic regulator comprises sodium chloride, glucose, fructose, glycerol, sorbitol, mannitol, etc.; the emulsifier comprises phospholipid, cholesterol, poloxamer, etc.; the matrix comprises: PEG6000, PEG4000 and the like.

The invention also aims to provide application of the pharmaceutical composition in preparing a medicament for preventing and treating cerebral infarction.

The atractylenolide II is one of active ingredients of a genuine medicinal material, namely rhizoma atractylodis macrocephalae in Heilongjiang province, and the prior art shows that the atractylenolide II has certain treatment effects on treating gastric ulcer, diarrhea, inflammation and senile dementia. Lovastatin is a common blood fat-reducing drug in the field, and modern researches show that the lovastatin has an obvious therapeutic effect on the aspect of preventing and treating cerebral infarction, and possible pharmacological mechanisms are prevention of thrombosis in blood vessels, and prevention and control of nerve cells through activation of eNOS, antioxidation and anti-inflammatory effects, so that the lovastatin has a neuroprotective effect. Considering that hyperlipidemia is one of the important factors for inducing cerebral infarction, lovastatin is a drug with great market prospect for preventing and treating cerebral infarction. The invention combines abundant medicinal plant resources in Heilongjiang province on the basis of lovastatin, and finds that the atractylenolide compound and the lovastatin show obvious synergistic effect in preventing and treating cerebral infarction. Furthermore, in order to facilitate clinical application and combine metabolic disorder symptoms of patients with cerebral infarction, the vitamin B in the bodies of the patients is deficient, so that the vitamin B component is additionally added into the composition, and the curative effect of the pharmaceutical composition is optimal.

Advantageous effects

The pharmaceutical composition provided by the invention has the advantages that the atractylenolide II, lovastatin and B vitamins are compounded and combined in a specific ratio for use, the cerebral infarction area is obviously reduced, the nervous function system is improved, the treatment effect obviously superior to that of single medicine is generated, and the effect of preventing and treating cerebral infarction is obvious.

Detailed Description

The present invention is described in more detail below to facilitate an understanding of the present invention.

It should be understood that the terms or words used in the specification and claims should not be construed as having meanings defined in dictionaries, but should be interpreted as having meanings that are consistent with their meanings in the context of the present invention on the basis of the following principles: the concept of terms may be defined appropriately by the inventors for the best explanation of the invention.