阅读说明：本技术 具有抑制凝血酶活性的药物组合物及其用途 (Pharmaceutical composition with thrombin activity inhibition function and application thereof ) 是由 高文远 王娟 姚陆 刘静静 许馨丹 贺军平 于 2019-09-06 设计创作，主要内容包括：本发明公开了具有抑制凝血酶活性的药物组合物及其用途,该药物组合物,包括如下组份：三七不定根粉末、西洋参提取物、黄芪提取物、川芎提取物、丹参提取物和当归提取物。本发明利用培养的三七不定根作为药物组合物主要组份,与其他组份配比的药物组合物具有抑制凝血酶活性,舒张血管和抗疲劳作用,能够应用在抑制凝血酶活性,舒张血管和抗疲劳的药物的制备中,为三七药物开发来源提供了一条新途径。(The invention discloses a pharmaceutical composition for inhibiting thrombin activity and application thereof, wherein the pharmaceutical composition comprises the following components: notoginseng radix adventitious root powder, radix Panacis Quinquefolii extract, radix astragali extract, rhizoma Ligustici Chuanxiong extract, Saviae Miltiorrhizae radix extract and radix Angelicae sinensis extract. The invention utilizes the cultured adventitious roots of the pseudo-ginseng as the main component of the pharmaceutical composition, the pharmaceutical composition which is matched with other components has the functions of inhibiting thrombin activity, relaxing blood vessels and resisting fatigue, can be applied to the preparation of drugs for inhibiting thrombin activity, relaxing blood vessels and resisting fatigue, and provides a new way for developing pseudo-ginseng drugs.)

1. A pharmaceutical composition for inhibiting thrombin activity is characterized by comprising the following components: notoginseng radix adventitious root powder, radix Panacis Quinquefolii extract, radix astragali extract, rhizoma Ligustici Chuanxiong extract, Saviae Miltiorrhizae radix extract and radix Angelicae sinensis extract.

2. The pharmaceutical composition of claim 1, wherein the ingredients comprise, by weight, 12-18 parts of adventitious root powder of notoginseng, 3-5 parts of American ginseng extract, 4-6 parts of astragalus extract, 2-5 parts of ligusticum wallichii extract, 3-6 parts of salvia miltiorrhiza extract and 2-4 parts of angelica sinensis extract.

3. The pharmaceutical composition of claim 2, wherein the powder of adventitious roots of notoginseng is 15 parts, the extract of american ginseng is 4 parts, the extract of astragalus is 5 parts, the extract of chuanxiong rhizome is 3 parts, the extract of salvia miltiorrhiza is 4 parts, and the extract of angelica is 3 parts.

4. Pharmaceutical composition according to one of claims 1 to 3, characterized in that the powder of adventitious roots of notoginseng is prepared by the following method:

(1) inducing adventitious roots of pseudo-ginseng;

(2) domestication culture and screening of the adventitious roots of the panax notoginseng: transferring the adventitious roots of the panax notoginseng obtained in the step (1) to a domestication culture medium for domestication and subculture, screening root systems according to the number of branches of the root systems, measuring the content of active ingredients, and culturing stable root systems with the screened root system branches of more than 3-5, and the total content of notoginsenoside and ginsenoside higher than 15mg/g dry weight at the temperature of 120-150rpm and 23-27 ℃ for 6-7 weeks;

the domestication culture medium is 11g/L SH +30g/L cane sugar +1mg/L NAA +3mg/L IBA, and the balance is water;

(3) culturing pseudo-ginseng adventitious roots in a reactor: inoculating the panax notoginseng adventitious roots screened in the step (2) into an airlift reactor containing an acclimatization culture medium, wherein the ventilation amount is 0.1vvm, and culturing for 8-10 weeks at room temperature;

(4) preparation of powder of pseudo-ginseng adventitious roots: drying and crushing the pseudo-ginseng adventitious roots obtained in the step (3) at 50-60 ℃, and sieving with a 100-mesh and 200-mesh sieve to obtain pseudo-ginseng adventitious root powder.

5. Use of a pharmaceutical composition according to any one of claims 1 to 4 in the manufacture of a medicament for inhibiting thrombin activity.

6. Use of a pharmaceutical composition according to any one of claims 1 to 4 in the manufacture of a medicament for promoting vasodilation.

7. Use of a pharmaceutical composition according to any one of claims 1 to 4 for the preparation of an antifatigue medicament.

Technical Field

The invention belongs to the field of biological medicine, and particularly relates to a pharmaceutical composition capable of inhibiting thrombin activity.

Background

Pseudo-ginseng is named as SHANQI, DIANQI, SHEN-QI, TIAN-QI, JIN-BU, NAO-SHEN-CAO, etc. The medicinal history of panax notoginseng is long, and panax notoginseng saponins and ginsenoside are main active ingredients of the panax notoginseng saponins and have the effects of resisting tumors and oxidation, promoting blood circulation, improving sleep, enhancing immunity, improving nervous system and the like. Due to the diversity of saponin activities, in recent years, notoginseng has been widely used in various health products and medicines. The market demand is increased year by year, and the market prospect is more and more extensive. But is limited by the characteristic that the continuous cropping can not be realized during the planting of the panax notoginseng, and the panax notoginseng is suitable for the exhaustion of land, thereby limiting the further development and application of the panax notoginseng to a certain extent. Radix Panacis Quinquefolii has protective effect on central nervous system and cardiovascular system. Radix astragali has effects of enhancing organism immunity, protecting liver, promoting urination, resisting aging, resisting stress, and lowering blood pressure. Rhizoma Ligustici Chuanxiong has effects of promoting blood circulation, activating qi-flowing, dispelling pathogenic wind and relieving pain. The Saviae Miltiorrhizae radix has effects of removing blood stasis, promoting tissue regeneration, promoting blood circulation, and regulating menstruation. The angelica has the effects of tonifying blood and blood, regulating menstruation, relieving pain, moistening dryness, lubricating intestines, resisting cancer, resisting aging and resisting immunity.

The adventitious roots are induced from the cultivated roots, have the same/similar genotype as the cultivated roots, and have similar effective components. Tissue culture of adventitious roots also has other advantages: (1) the production cycle is short, and a large amount of tissues and active ingredients can be obtained in a short time; (2) the method is not limited by seasons and regions, and large-scale production can be realized; (3) and the damage to the environment caused by improper field planting is relieved to a certain extent. However, at present, no report exists that the adventitious roots of the panax notoginseng are directly utilized to form a pharmaceutical composition with thrombin inhibition activity.

Disclosure of Invention

The invention aims to overcome the defects of the prior art and provide a pharmaceutical composition capable of inhibiting thrombin activity.

The second purpose of the invention is to provide the application of the pharmaceutical composition with thrombin activity inhibition in preparing drugs for inhibiting thrombin activity.

The third purpose of the invention is to provide the application of the pharmaceutical composition with the thrombin inhibiting activity in preparing the vasodilation promoting medicine.

The fourth purpose of the invention is to provide the application of the pharmaceutical composition with thrombin inhibiting activity in preparing the anti-fatigue medicine.

The technical scheme of the invention is summarized as follows:

a pharmaceutical composition for inhibiting thrombin activity comprises the following components: notoginseng radix adventitious root powder, radix Panacis Quinquefolii extract, radix astragali extract, rhizoma Ligustici Chuanxiong extract, Saviae Miltiorrhizae radix extract and radix Angelicae sinensis extract.

Preferably, the components comprise, by weight, 12-18 parts of pseudo-ginseng adventitious root powder, 3-5 parts of American ginseng extract, 4-6 parts of astragalus extract, 2-5 parts of ligusticum wallichii extract, 3-6 parts of salvia miltiorrhiza extract and 2-4 parts of angelica sinensis extract.

Preferably, the powder of adventitious roots of pseudo-ginseng is 15 parts, the extract of American ginseng is 4 parts, the extract of astragalus is 5 parts, the extract of ligusticum wallichii is 3 parts, the extract of salvia miltiorrhiza is 4 parts, and the extract of angelica is 3 parts.

The medicinal composition is prepared from the pseudo-ginseng adventitious root powder by the following method:

(1) inducing adventitious roots of pseudo-ginseng;

(2) domestication culture and screening of the adventitious roots of the panax notoginseng: transferring the adventitious roots of the panax notoginseng obtained in the step (1) to a domestication culture medium for domestication and subculture, screening root systems according to the number of branches of the root systems, measuring the content of active ingredients, and culturing stable root systems with the screened root system branches of more than 3-5, and the total content of notoginsenoside and ginsenoside higher than 15mg/g dry weight at the temperature of 120-150rpm and 23-27 ℃ for 6-7 weeks;

the domestication culture medium is 11g/L SH +30g/L cane sugar +1mg/L NAA +3mg/L IBA, and the balance is water;

(3) culturing pseudo-ginseng adventitious roots in a reactor: inoculating the panax notoginseng adventitious roots screened in the step (2) into an airlift reactor containing an acclimatization culture medium, wherein the ventilation amount is 0.1vvm, and culturing for 8-10 weeks at room temperature;

(4) preparation of powder of pseudo-ginseng adventitious roots: drying and crushing the pseudo-ginseng adventitious roots obtained in the step (3) at 50-60 ℃, and sieving with a 100-mesh and 200-mesh sieve to obtain pseudo-ginseng adventitious root powder.

The application of the pharmaceutical composition in preparing medicines for inhibiting thrombin activity.

The application of the pharmaceutical composition in preparing vasodilation promoting medicines.

The application of the pharmaceutical composition in preparing anti-fatigue drugs.

THE ADVANTAGES OF THE PRESENT INVENTION

The invention utilizes the cultured adventitious roots of the pseudo-ginseng as the main component of the pharmaceutical composition, the pharmaceutical composition which is matched with other components has the functions of inhibiting thrombin activity, relaxing blood vessels and resisting fatigue, can be applied to the preparation of drugs for inhibiting thrombin activity, relaxing blood vessels and resisting fatigue, and provides a new way for developing pseudo-ginseng drugs.

Drawings

FIG. 1 is a graph showing the effect of the pharmaceutical composition having thrombin activity inhibiting activity prepared in example 4 on thrombin activity.

FIG. 2 is a graph showing the effect of the pharmaceutical composition having thrombin inhibitory activity prepared in example 4 on the vasodilator activity of superior mesenteric arteries in rats.

FIG. 3 is a graph showing the effect of the pharmaceutical composition having thrombin inhibitory activity prepared in example 4 on rat hypothalamus 5-HT.

Detailed Description

The present invention will be further illustrated by the following specific examples.

The notoginseng adventitious root powder is prepared by the following method:

(1) induction of adventitious roots of pseudo-ginseng: cleaning fresh Notoginseng radix, sterilizing with 75% ethanol water solution, cutting into 1-1.5cm in clean bench²Inoculating the small pieces into a callus induction culture medium, and culturing for 3-4 weeks at 23-27 ℃ in a dark place to obtain visible callus; transferring the callus to an adventitious root induction culture medium for continuous induction, and culturing at 25 ℃ in the dark for 3-4 weeks to form adventitious roots;

callus induction medium: MS + 3% sucrose +3 mg/L2, 4-D +1.5 mg/L6-BA solid medium;

adventitious root induction medium: MS + 3% of cane sugar +1.0mg/L of KT +2.0mg/L of IBA solid culture medium;

(2) domestication culture and screening of the adventitious roots of the panax notoginseng: transferring the adventitious roots of the panax notoginseng obtained in the step (1) to a domestication culture medium for domestication and subculture, screening root systems according to the number of branches of the root systems, measuring the content of active ingredients, and culturing stable root systems with the screened root system branches of more than 3-5, and the total content of notoginsenoside and ginsenoside higher than 15mg/g dry weight at the temperature of 120-150rpm and 23-27 ℃ for 6-7 weeks;

the domestication culture medium is 11g/L SH +30g/L cane sugar +1mg/L NAA +3mg/L IBA, and the balance is water;

(3) culturing pseudo-ginseng adventitious roots in a reactor: inoculating the screened adventitious roots of the panax notoginseng obtained in the step (2) into an airlift reactor containing an acclimatization culture medium, wherein the ventilation amount is 0.1vvm, and culturing for 8-10 weeks at room temperature;

(4) preparation of powder of pseudo-ginseng adventitious roots: drying and crushing the pseudo-ginseng adventitious roots obtained in the step (3) at 50-60 ℃, and sieving with a 100-mesh and 200-mesh sieve to obtain pseudo-ginseng adventitious root powder.

The American ginseng extract is commercially available: the content of total saponins is greater than or equal to 80%.

The astragalus extract is commercially available: the purity is more than or equal to 60 percent.

The chuanxiong rhizome extract is commercially available: the purity is more than or equal to 75 percent.

The salvia miltiorrhiza extract is commercially available: the purity is more than or equal to 85 percent.

The angelica extract is commercially available: the purity is more than or equal to 80 percent.

Parts by weight for each example may be grams, kilograms or other units of weight.

For each example:

callus induction medium: MS + 3% sucrose +3 mg/L2, 4-D +1.5 mg/L6-BA solid medium;

adventitious root induction medium: MS + 3% of cane sugar +1.0mg/L of KT +2.0mg/L of IBA solid culture medium;

the domestication culture medium is 11g/L SH +30g/L cane sugar +1mg/L NAA +3mg/L IBA, and the balance is water;