A thrombolytic composition comprising a plant extract and a bio-enzyme, and a preparation method and application thereof

Abstract

The application belongs to the technical field of biological medicine, and discloses a thrombolytic composition containing plant extracts and biological enzymes, and a preparation method and application thereof. The composition contains the following components in parts by weight: natto kinase 50-200 parts; lumbrukinase 10-50 parts; angelica extract 10-100 parts; turmeric extract 10-100 parts; brown algae extract 5-50 parts; protective agent: mannitol 0.2-0.5 parts, edible gelatin 0.5-5 parts, and sodium bicarbonate 0.1-2 parts. The application realizes the synergistic antithrombotic effect of multiple mechanisms and multiple targets through the direct thrombolytic effect of natto kinase and lumbrukinase, and the anti-platelet aggregation, anti-inflammatory and anticoagulation effects of angelica, turmeric and brown algae, and improves the oral bioavailability. The ingredients with the same origin of medicine in the formula help to improve the microcirculation and protect the vascular endothelium. Compared with traditional chemical drugs, the composition has higher safety and smaller side effects, and is suitable for long-term prevention and rehabilitation.

Description

Technical Field

[0001] This invention relates to the field of biomedical technology, specifically to a thrombolytic composition comprising plant extracts and biological enzymes, its preparation method, and its applications, primarily for the preparation of drugs and health foods for the prevention of thrombosis. Background Technology

[0002] Thrombotic diseases seriously threaten human health. Thrombolytic therapy is a key means to restore blood vessel recanalization and save ischemic tissue. Its core lies in rapidly and effectively degrading fibrin and dissolving thrombi.

[0003] Existing thrombolytic drugs such as streptokinase and urokinase have drawbacks including high bleeding risk, short half-life, and high cost. While nattokinase and lumbrokinase are highly safe, they suffer from low oral bioavailability and are susceptible to degradation by stomach acid. Traditional Chinese medicines such as angelica, turmeric, and brown algae have traditional effects of promoting blood circulation, removing blood stasis, and preventing thrombosis, but their active ingredients have low solubility and limited targeting in vivo.

[0004] Therefore, developing a highly efficient, safe, and stable oral thrombolytic composition has significant clinical and market value. Summary of the Invention

[0005] To overcome the shortcomings of existing technologies, this invention focuses on achieving the purpose of thrombus prevention and dissolution through a synergistic strategy of "multi-target, multi-pathway". The components complement each other, covering multiple stages of thrombus formation. For anti-platelet aggregation, angelica, curcumin, and fucoidan sulfate are used; for direct fibrin degradation (thrombolysis), nattokinase and lumbrokinase are used; for anti-inflammation and vascular endothelial protection, curcumin, fucoidan sulfate, and angelica are used. In addition, fucoidan sulfate has both anticoagulant and antithrombotic effects; nattokinase can also activate the endogenous fibrinolytic system. This combination of multiple mechanisms of action can achieve a faster and more stable thrombolytic effect while also preventing thrombosis. Currently, no patents or applications of thrombolytic formulas containing all five of the above components have been found, therefore, this invention possesses a certain degree of originality.

[0006] The technical solution adopted by this invention to solve its technical problem is as follows: A thrombolytic composition comprising plant extracts and bioenzymes, comprising the following components in parts by weight: Nattokinase: 50-200 servings; Lumbrokinase: 10-50 parts; Angelica sinensis extract: 10-100 parts; Turmeric extract: 10-100 parts; Brown algae extract: 5-50 parts; Protective agents: mannitol: 0.2-0.5 parts, edible gelatin: 0.5-5 parts, sodium bicarbonate: 0.1-2 parts.

[0007] Furthermore, the content of brown algae extract containing brown algae polysaccharide sulfate is not less than 30% by mass.

[0008] Optionally, the composition may further comprise pharmaceutically acceptable excipients, such as sorbic acid and its potassium salt, tea polyphenols, chitosan, vitamin E, etc.

[0009] A method for preparing a thrombolytic composition comprising plant extracts and bioenzymes includes the following steps: (1) Dissolving and mixing: The above composition was mixed at room temperature and dissolved in 100 mL of purified water to form a mixture. (2) Aseptic treatment of the mixture: use a sterile membrane with a pore size of less than or equal to 0.22 μm for filtration, and all utensils must be subjected to high pressure or harmless disinfection in advance; (3) Prepare enzyme-containing microspheres or powder.

[0010] Furthermore, the composition can also be prepared into granules, but oral formulations, including tablets or capsules, are not excluded.

[0011] Furthermore, the preparation of microspheres includes the following steps: (4) Solution pretreatment Take the sterile mixture from step (2), add dextrin at a mass ratio of 1:10-30, and then mix in 5-15% volume of adhesive to make wet material; (5) Granulation and drying The wet material prepared in step (4) is added to a wet mixing granulator. After the mixture is extruded and rolled into wet microspheres, it is dried at low temperature using a fluidized bed or oven. The temperature is usually controlled at 30-45℃ to avoid high temperature damage to enzyme activity.

[0012] Furthermore, a vibrating fluidized bed dryer is preferred, employing multi-zone temperature control (3-5 zones) and heat pump (temperature control within 38℃) to assist dehumidification. From the inlet to the outlet, the temperature decreases gradually, dividing the dryer into 3-5 independent zones. Temperatures are independently set according to the material's moisture content and state, achieving gradient drying and maximizing the protection of heat-sensitive components. This process achieves both efficient dehydration and maximum protection of the heat-sensitive active ingredients in the material, realizing a precise "step-down temperature drying" process. The resulting micro-pellets offer better protection of active ingredients during processing and storage compared to liquids and powders.

[0013] Furthermore, the adhesive in step (4) is 60% by volume edible alcohol.

[0014] Furthermore, the preparation of microspheres also includes packaging and storage steps.

[0015] Furthermore, the nattokinase activity in the enzyme-containing microcapsules or powder is 100-400 FU / g; the lumbrokinase activity is 60,000-120,000 U / g.

[0016] The above composition is used in the preparation of functional foods or medicines for the treatment or prevention of thrombotic diseases.

[0017] Compared with the prior art, the beneficial effects of the present invention include: This invention achieves a synergistic antithrombotic effect through the direct thrombolytic action of nattokinase and lumbrokinase, combined with the antiplatelet aggregation, anti-inflammatory, and anticoagulant effects of angelica, turmeric, and brown algae. The use of gelatin as a bioenzyme protectant and sodium bicarbonate to neutralize gastric acid effectively protects enzyme activity in the acidic gastric environment, improving oral bioavailability. The food-and-medicine homologous components in the formula help improve microcirculation and protect vascular endothelium, embodying the principle of "treating both the symptoms (thrombolysis) and the root cause (improving vascular health)." Compared to traditional chemical drugs, the composition of this invention has higher safety, fewer side effects, and is suitable for long-term prevention and rehabilitation. Detailed Implementation

[0018] The technical solutions of the present invention will now be clearly and completely described. Obviously, the described embodiments are only some, not all, of the embodiments of the present invention. Based on the embodiments of the present invention, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of the present invention.

[0019] Furthermore, the technical features involved in the different embodiments of the present invention described below can be combined with each other as long as they do not conflict with each other.

[0020] Example 1 Nattokinase (200 mg), Lumbrokinase (0.05 mg), Angelica sinensis extract (40 mg), Curcuma longa extract (10 mg, containing 95% curcumin), brown algae extract (20 mg, containing 40% brown algae polysaccharide sulfate), edible gelatin 5 mg, sodium bicarbonate 0.5 mg.

[0021] Example 2 Nattokinase (250 mg), Lumbrokinase (0.1 mg), Angelica sinensis extract (30 mg), Curcuma longa extract (20 mg, containing 95% curcumin), brown algae extract (15 mg, containing 40% brown algae polysaccharide sulfate), edible gelatin 2.5 mg, sodium bicarbonate 1 mg.

[0022] Example 3 Nattokinase (100 mg), Lumbrokinase (0.2 mg), Angelica sinensis extract (30 mg), Curcuma longa extract (10 mg, containing 95% curcumin), Brown algae extract (30 mg, containing 40% by weight of brown algae polysaccharide sulfate), edible gelatin 5 mg, sodium bicarbonate 2 mg.

[0023] Example 4 To protect enzyme activity and achieve targeted release, ensuring its stability and solubility in beverages, the following steps are illustrated in the formulation example: (1) Dissolving and mixing: 200 parts of nattokinase and 50 parts of lumbrokinase (lyophilized powder) containing enzyme solutions of appropriate concentrations were mixed at room temperature and dissolved in 100 mL of purified water to form a mixture.

[0024] (2) Aseptic treatment of the mixture: Filter through a 0.22μm (or smaller pore size) sterile membrane of a stainless steel filter. All utensils must be autoclaved or sterilized in advance.

[0025] (3) Prepare enzyme-containing microspheres or powder.

[0026] Example 5 Microparticles were prepared using the following standard process route: (1) Solution pretreatment The above-mentioned aseptically treated mixture is mixed with dextrin at a mass ratio of 1:20, and then mixed with 10% by volume of binder (60% by volume of edible alcohol) to form a wet material.

[0027] (2) Core granulation (granulation & drying) In a wet mixing granulator, the mixture is extruded and rolled into wet microspheres, which are then dried at low temperature using a fluidized bed or oven. The temperature is usually controlled at 30-45℃ to avoid damaging enzyme activity due to high temperature.

[0028] The vibrating fluidized bed dryer features multi-zone temperature control (3-5 zones) and heat pump-assisted dehumidification (temperature control within 38℃). From the inlet to the outlet, the temperature decreases gradually, dividing the dryer into 3-5 independent zones. Temperatures are independently set according to the material's moisture content and state, achieving gradient drying and maximizing the protection of heat-sensitive components. This highly efficient dehydration process effectively preserves the heat-sensitive active ingredients in the material, achieving a precise "step-down temperature drying" process. The resulting micro-pellets offer better protection of active ingredients during processing and storage compared to liquids and powders.

[0029] (3) Automatic packaging machine: vertical or horizontal, suitable for clean areas and supports modified atmosphere packaging.

[0030] It can also be used to make solid beverages by directly mixing nattokinase with various plant powders and extracts; store in a cool, dry environment away from light.

[0031] Product indicator reference: The product added directly can be flexibly adjusted according to needs. The nattokinase activity is 100-400 FU / g; the lumbrokinase activity is 60,000-120,000 U / g.

[0032] Obviously, the above embodiments are merely illustrative examples for clear explanation and are not intended to limit the implementation. Those skilled in the art will recognize that other variations or modifications can be made based on the above description. It is neither necessary nor possible to exhaustively list all possible implementations here. However, obvious variations or modifications derived therefrom are still within the scope of protection of this invention.

Claims

1. A thrombolytic composition comprising plant extracts and biological enzymes, characterized in that, It contains the following components in parts by weight: Nattokinase: 50-200 servings; Lumbrokinase: 10-50 parts; Angelica sinensis extract: 10-100 parts; Turmeric extract: 10-100 parts; Brown algae extract: 5-50 parts; Protective agents: mannitol: 0.2-0.5 parts, edible gelatin: 0.5-5 parts, sodium bicarbonate: 0.1-2 parts.

2. The thrombolytic composition comprising plant extracts and biological enzymes according to claim 1, characterized in that, The content of brown algae extract in the extract is not less than 30% by mass.

3. The thrombolytic composition comprising plant extracts and biological enzymes according to claim 1, characterized in that, The composition also contains sorbic acid and its potassium salt, tea polyphenols, chitosan, and vitamin E.

4. A method for preparing a thrombolytic composition comprising plant extracts and biological enzymes as described in claim 1, characterized in that, Includes the following steps: (1) Dissolving and mixing: The above composition was mixed at room temperature and dissolved in 100 mL of purified water to form a mixture. (2) Aseptic treatment of the mixture: use a sterile membrane with a pore size of less than or equal to 0.22 μm for filtration, and all utensils must be subjected to high pressure or harmless disinfection in advance; (3) Prepare enzyme-containing microspheres or powder.

5. The composition according to claim 1, characterized in that, It can also be prepared into granules, tablets or capsules.

6. The preparation method according to claim 4, characterized in that, The preparation of microspheres includes the following steps: (4) Solution pretreatment Take the sterile mixture from step (2), add dextrin at a mass ratio of 1:10-30, and then mix in 5-15% volume of adhesive to make wet material; (5) Granulation and drying The wet material prepared in step (4) is added to a wet mixing granulator. After the mixture is extruded and rolled into wet microspheres, it is dried at low temperature using a fluidized bed or oven. The temperature is controlled at 30-45℃ to avoid high temperature damage to enzyme activity.

7. The preparation method according to claim 6, characterized in that, The fluidized bed is a vibrating fluidized bed dryer with 3-5 temperature control stages. The binder in step (4) is 60% edible alcohol by volume.

8. The preparation method according to claim 5, characterized in that, The nattokinase activity in the enzyme-containing microcapsules or powder is 100-400 FU / g; the lumbrokinase activity is 60,000-120,000 U / g.

9. The preparation method according to claim 6, characterized in that, The preparation of microspheres also includes packaging and storage steps.

10. An application of the composition as claimed in claim 1, characterized in that, Prepare functional foods or drugs for the treatment or prevention of thrombotic diseases.