A traditional Chinese medicine composition and its application for clearing blood vessels, dissolving blood spots, regulating the five internal organs, and preventing and treating atherosclerosis and its related coronary heart disease, hypertension, hyperlipidemia, hyperglycemia, hyperuricemia, diabetic gangrene.

Abstract

This invention discloses a traditional Chinese medicine composition and its application for clearing blood vessels, dissolving blood spots, regulating the five internal organs, and preventing and treating arteriosclerosis and its associated coronary heart disease, hypertension, hyperlipidemia, hyperglycemia, hyperuricemia, and diabetic gangrene. It belongs to the field of traditional Chinese medicine composition technology. The preparation method of the traditional Chinese medicine composition is as follows: (1) treating *Salvia miltiorrhiza*, *Polygonatum sibiricum*, and *Polygonum multiflorum* with alcohol using ultrasound to obtain an alcohol extract and residue; (2) extracting *Lycium barbarum*, *Epimedium brevicornu*, *Ligustrum lucidum*, *Angelica sinensis*, *Cuscuta chinensis*, *Astragalus membranaceus*, *Crataegus pinnatifida*, *Ziziphus jujuba*, *Chrysanthemum morifolium*, and *Lycium chinense* with water to obtain an aqueous extract; (3) mixing the residue and aqueous extract and enzymatically hydrolyzing to obtain an enzymatic hydrolysate; (4) mixing the alcohol extract and enzymatic hydrolysate and drying. The enzymes are yeast extractase, cellulase, and bromelain in a mass ratio of 0.5-1:1:0.1-0.3. Compared with existing technologies, this invention can improve microcirculation disorders and can be used to prevent and treat various diseases caused by microvascular circulation disorders.

Description

Technical Field

[0001] This invention belongs to the field of traditional Chinese medicine composition technology. Specifically, it relates to a traditional Chinese medicine composition and its application for clearing blood vessels, dissolving blood spots, regulating the five internal organs, preventing and treating arteriosclerosis and its associated coronary heart disease, hypertension, hyperlipidemia, hyperglycemia, hyperuricemia, and diabetic gangrene. Background Technology

[0002] Kangxin Oral Liquid / Capsules is a traditional Chinese medicine preparation produced by Jilin Huakang Pharmaceutical Co., Ltd. It mainly includes wolfberry, prepared Polygonum multiflorum, Epimedium, Ligustrum lucidum, Angelica sinensis, Cuscuta chinensis, Astragalus membranaceus, prepared Polygonatum sibiricum, Salvia miltiorrhiza, hawthorn, Ziziphus jujuba var. spinosa, chrysanthemum, and Lycium chinense root bark. It has the functions of tonifying the kidneys and replenishing essence, strengthening the spleen and replenishing qi, nourishing blood and promoting blood circulation. It is suitable for fatigue, lower back and knee weakness, insomnia, forgetfulness, and post-illness weakness caused by deficiency of both spleen and kidney and insufficient qi and blood.

[0003] Wu Tianmin et al. (Interventional effect of Kangxin capsules on carotid atherosclerotic plaques [J], Journal of Fujian University of Traditional Chinese Medicine, 2007, 17(3), 12-15) found that Kangxin capsules have a certain degree of effect in reducing and stabilizing atherosclerotic plaques. After treatment with Kangxin capsules, carotid IMT, Crouse score, area, blood lipids, hs-CRP and Fib were all significantly lower than before treatment (P<0.05 or P<0.01). Based on this, CN118806855A disclosed a traditional Chinese medicine composition for the prevention and treatment of coronary heart disease, hypertension, hyperlipidemia, hyperglycemia or hyperuricemia gout caused by arteriosclerosis. This invention modifies the preparation process of Kangxin oral liquid / capsule. Compared with the original product, its efficacy has been significantly improved, and it can effectively prevent and treat coronary heart disease, hypertension, hyperlipidemia, hyperglycemia or hyperuricemia gout caused by arteriosclerosis.

[0004] Kangxin Oral Liquid / Capsules were developed based on the formulas of "Shenxian Xunlao Wan" and "Shenxian Bulao Wan" recorded in the Yongle Encyclopedia. Further developing its efficacy and maximizing the medicinal value of the ancient formula is of great significance. Summary of the Invention

[0005] To address the aforementioned technical problems, this invention provides a traditional Chinese medicine composition for clearing blood vessels, dissolving blood spots, regulating the five internal organs, and preventing and treating atherosclerosis and its associated coronary heart disease, hypertension, hyperlipidemia, hyperglycemia, hyperuricemia, and diabetic gangrene. This invention improves the preparation method by utilizing the co-extraction of Salvia miltiorrhiza, Polygonatum sibiricum, and Polygonum multiflorum, avoiding the loss of active ingredients among the components. This maximizes the effects of clearing blood vessels, dissolving blood spots, and regulating the five internal organs, and has a good therapeutic effect on preventing and treating atherosclerosis and its associated coronary heart disease, hypertension, hyperlipidemia, hyperglycemia, hyperuricemia, and diabetic gangrene.

[0006] To achieve the above objectives, the present invention adopts the following technical solution:

[0007] In a first aspect, the present invention provides a traditional Chinese medicine composition for clearing blood vessels, dissolving blood spots, regulating the five internal organs, and preventing and treating arteriosclerosis and its associated coronary heart disease, hypertension, hyperlipidemia, hyperglycemia, hyperuricemia, and diabetic gangrene. The preparation method of the traditional Chinese medicine composition includes the following steps:

[0008] (1) White-flowered Salvia miltiorrhiza, Polygonatum sibiricum and Polygonum multiflorum were subjected to ultrasonic treatment with alcohol, and solid-liquid separation was performed to obtain alcohol extract and residue;

[0009] (2) Extract the following ingredients with water: wolfberry, epimedium, privet fruit, angelica, dodder seed, astragalus, hawthorn, jujube seed, chrysanthemum and lycium bark to obtain water extract;

[0010] (3) Mix the dregs and water extracts together for enzymatic hydrolysis, and separate the solid and liquid components to obtain the hydrolysate;

[0011] (4) Mix the alcohol extract and the enzyme hydrolysate, and dry them to obtain the final product.

[0012] In some implementations, the alcohol in step (1) is ethanol with a volume fraction of 90%-95%.

[0013] In some implementations, the ultrasonic treatment in step (1) is: temperature 40℃-50℃, power 300 W-500W, time 15 min-30 min.

[0014] In some implementations, the water extraction in step (2) is performed by boiling in water, and the water extraction is performed 1-3 times, with each extraction lasting 0.5-2 hours.

[0015] In some implementations, the enzymes used in step (3) for enzymatic hydrolysis are yeast extractase, cellulase and bromelain.

[0016] In some embodiments, the mass ratio of the yeast extractase, cellulase, and bromelain is 0.5-1:1:0.1-0.3.

[0017] In some implementations, the enzymatic hydrolysis temperature in step (3) is 50℃-55℃ and the enzymatic hydrolysis time is 2 h-6 h.

[0018] In some embodiments, the preparation method of the traditional Chinese medicine composition is as follows:

[0019] (1) Add 90%-95% ethanol to white salvia miltiorrhiza, polygonatum and he shou wu at a material-liquid ratio of 1:8-15, sonicate at 40℃-50℃ (300W-500W) for 15 min-30 min, filter to obtain ethanol extract and residue.

[0020] (2) Add water to wolfberry, epimedium, privet fruit, angelica, dodder seed, astragalus, hawthorn, jujube seed, chrysanthemum and lycium bark at a mass ratio of 1:10-15 and decoct once for 0.5-2 hours to obtain water extract;

[0021] (3) Mix the dregs and water extract, cool to 50℃-55℃, add enzyme and react for 2h-6h, filter to obtain enzyme hydrolysate;

[0022] The enzymes are yeast extractase, cellulase, and bromelain, and the mass ratio of the yeast extractase, cellulase, and bromelain is 0.5-1:1:0.1-0.3.

[0023] The amount of enzyme added is 0.3%-1% of the water extract mass.

[0024] (4) Mix the alcohol extract and the enzyme hydrolysate and dry under reduced pressure to obtain the final product.

[0025] In some embodiments, the traditional Chinese medicine composition is made from the following raw materials in parts by weight: 15-20 parts of wolfberry, 15-20 parts of fleeceflower root, 15-20 parts of epimedium, 15-20 parts of privet fruit, 22-26 parts of angelica root, 34-38 parts of dodder seed, 25-30 parts of astragalus root, 34-38 parts of polygonatum rhizome, 15-20 parts of salvia root, 25-30 parts of hawthorn fruit, 15-20 parts of jujube seed, 34-38 parts of chrysanthemum flower, and 15-20 parts of lycium root bark.

[0026] In some embodiments, the traditional Chinese medicine composition is made from the following raw materials in parts by weight: 18-20 parts of wolfberry, 18-20 parts of fleeceflower root, 18-20 parts of epimedium, 18-20 parts of privet fruit, 24-26 parts of angelica root, 36-38 parts of dodder seed, 27-30 parts of astragalus root, 36-38 parts of polygonatum rhizome, 18-20 parts of salvia root, 27-30 parts of hawthorn fruit, 18-20 parts of jujube seed, 36-38 parts of chrysanthemum flower, and 18-20 parts of lycium root bark.

[0027] In some embodiments, the traditional Chinese medicine composition is made from the following raw materials in parts by weight: 15-18 parts of wolfberry, 15-18 parts of fleeceflower root, 15-18 parts of epimedium, 15-18 parts of privet fruit, 22-24 parts of angelica root, 34-36 parts of dodder seed, 25-27 parts of astragalus root, 34-36 parts of polygonatum rhizome, 15-18 parts of salvia root, 25-27 parts of hawthorn fruit, 15-18 parts of jujube seed, 34-36 parts of chrysanthemum flower, and 15-18 parts of lycium root bark.

[0028] In some embodiments, the traditional Chinese medicine composition is made from the following raw materials in parts by weight: 18 parts of wolfberry, 18 parts of fleeceflower root, 18 parts of epimedium, 18 parts of privet fruit, 24 parts of angelica, 36 parts of dodder seed, 27 parts of astragalus, 36 parts of polygonatum, 18 parts of salvia miltiorrhiza, 27 parts of hawthorn, 18 parts of jujube seed, 36 parts of chrysanthemum and 18 parts of lycium bark.

[0029] Secondly, the present invention provides the application of the above-mentioned traditional Chinese medicine composition in the preparation of a medicament for improving circulatory disorders.

[0030] The traditional Chinese medicine composition of the present invention has a significant inhibitory effect on the "three highs" phenomenon in the hemorheology of diabetes (i.e., high blood viscosity, high platelet aggregation, and high capillary permeability), and can be used as a microcirculation improver to prevent and treat various diseases caused by microvascular circulation disorders.

[0031] In some implementations, the circulatory disorder is diabetic gangrene of the extremities.

[0032] Thirdly, the present invention provides the application of the above-mentioned traditional Chinese medicine composition in the preparation of drugs for preventing and treating coronary heart disease, hypertension, hyperlipidemia, hyperglycemia, hyperuricemia, and diabetic gangrene caused by atherosclerosis.

[0033] Fourthly, the present invention provides a pharmaceutical preparation comprising the above-mentioned traditional Chinese medicine composition and pharmaceutically acceptable excipients.

[0034] In some embodiments, the dosage form of the pharmaceutical preparation is tablets, granules, capsules, pills, powders, syrups, or mixtures.

[0035] The beneficial effects of this invention are as follows:

[0036] (1) This invention utilizes a compound of white-flowered Salvia miltiorrhiza, nine-steamed and nine-dried Polygonatum sibiricum and nine-steamed and nine-dried Polygonum multiflorum for alcohol extraction, which can avoid the loss of active ingredients between components and maximize the effects of clearing blood vessels, dissolving blood spots and regulating the five internal organs. The alcohol extraction residue and the water extracts of Lycium barbarum, Epimedium, Ligustrum lucidum, Angelica sinensis, Cuscuta chinensis, Astragalus membranaceus, Crataegus pinnatifida, Ziziphus jujuba var. spinosa, Chrysanthemum morifolium and Lycium chinense root bark are enzymatically hydrolyzed with yeast extractase, cellulase and bromelain, which can destroy the cell wall and release more active ingredients. At the same time, it can degrade macromolecules and improve bioavailability.

[0037] (2) The traditional Chinese medicine composition of the present invention utilizes the aqueous extract prepared from wolfberry, epimedium, privet fruit, angelica, dodder seed, astragalus, hawthorn, jujube seed, chrysanthemum and lycium bark, mixed with yeast extractase, cellulase and bromelain, which can enhance enzyme activity, reduce enzyme dosage and lower production costs.

[0038] (3) Compared with the prior art, the traditional Chinese medicine composition of the present invention has a significant inhibitory effect on the “three highs” phenomenon in the blood rheology of diabetes, namely, high permeability of capillaries, high viscosity of blood and high aggregation of platelets. It can be used as a microcirculation improver to prevent and treat a variety of diseases caused by microvascular circulation disorders, especially diabetic gangrene of the extremities.

[0039] (4) The traditional Chinese medicine composition of the present invention has a simple process, low cost, and is more suitable for clinical application. Detailed Implementation

[0040] The following description of the embodiments is merely to aid in understanding the method and core ideas of the present invention. It should be noted that those skilled in the art can make various improvements and modifications to the present invention without departing from its principles, and these improvements and modifications also fall within the scope of the claims. The following description of the disclosed embodiments enables those skilled in the art to implement or use the present invention. Various modifications to these embodiments will be readily apparent to those skilled in the art, and the general principles defined herein may be implemented in other embodiments without departing from the spirit or scope of the invention. Therefore, the present invention is not limited to the embodiments shown herein, but can be applied to a wider scope consistent with the principles and novel features disclosed herein. While any methods and materials similar to or equivalent to those described herein may be used in the implementation or testing of the present invention, preferred methods and materials are listed herein.

[0041] Unless otherwise defined, all technical and scientific terms used in this invention have the same meaning as commonly understood by one of ordinary skill in the art to which this invention pertains.

[0042] The "pharmaceutical preparation" described in this invention includes the above-mentioned traditional Chinese medicine composition and pharmaceutically acceptable excipients. In specific embodiments, the traditional Chinese medicine composition described in this invention is provided in the pharmaceutical preparation in an effective amount (e.g., a therapeutically effective amount).

[0043] The "acceptable" ingredients described in this invention are substances suitable for human and / or animal use without excessive adverse side effects (such as toxicity, irritation, and allergic reactions), i.e., having a reasonable benefit / risk ratio. The "pharmaceuticalally acceptable excipients" include inert diluents, dispersants and / or granulators, surfactants and / or emulsifiers, disintegrants, binders, preservatives, buffers, lubricants, and / or oils. Excipients, colorants, coating agents, sweeteners, and flavoring agents may also be present in the pharmaceutical formulation.

[0044] The "pharmaceutical formulation" described in this invention can be prepared by any method known in pharmaceutical science. Generally, these preparation methods involve associating the traditional Chinese medicine composition (hereinafter referred to as the active ingredient) with a carrier or excipient and / or one or more other auxiliary ingredients, and then, if desired and / or expected, shaping and / or packaging the product into desired single-dose or multi-dose units.

[0045] The "pharmaceutical formulation" of this invention can be prepared according to known methods, such as those described in the general rules for preparation in the Chinese Pharmacopoeia 2020, the Japanese Pharmacopoeia 16th Edition, the United States Pharmacopoeia, and the European Pharmacopoeia 9th Edition. The specific preparation method depends on the dosage form.

[0046] The active ingredient and pharmaceutically acceptable excipients in the "pharmaceutical formulation" described in this invention will vary depending on the identity, body type, and / or condition of the treated subject and further on the route of administration of the active ingredient. The pharmaceutical formulation may contain between 0.1% and 100% (w / w) of the active ingredient.

[0047] As used herein, “treatment” means, unless otherwise stated, reversing or alleviating the condition or disease to which the term applies, or one or more symptoms of such condition or disease, inhibiting the progression of said condition or disease or one or more symptoms thereof, or preventing said condition or disease or one or more symptoms thereof. As used in this invention, the term “treatment” refers to a therapeutic act, as defined above.

[0048] The term "effective amount" as used in this invention refers to an amount sufficient to elicit the desired biological response. The effective amount of the active ingredient of this invention may vary depending on factors such as the desired biological endpoint, the pharmacokinetics of the compound, the condition being treated, the administration pattern, and the age and health status of the subject. In some embodiments, the effective amount is a therapeutically effective amount. The effective amount is the amount of the sole active ingredient described in this invention in a single dose. In some embodiments, the effective amount is a combination of the sole active ingredient described in this invention in multiple doses.

[0049] The term "therapeuticly effective amount" as used in this invention refers to an amount sufficient to provide therapeutic benefit in the treatment of a condition or sufficient to delay or minimize one or more symptoms associated with that condition. A therapeutically effective amount of an active ingredient means an amount in which the therapeutic agent, alone or in combination with other therapies, provides therapeutic benefit in the treatment of a condition. The term "therapeuticly effective amount" may encompass amounts that improve overall therapy, reduce or avoid symptoms, signs, or causes of a condition, and / or enhance the therapeutic efficacy of another therapeutic agent. In some embodiments, a therapeutically effective amount is an amount sufficient to treat any of the diseases or conditions described.

[0050] All raw materials used in this invention are conventional commercial products. Therefore, this invention does not limit the source of raw materials. It is worth noting that the Polygonatum sibiricum mentioned in this embodiment is Polygonatum sibiricum that has been steamed and dried nine times; the Polygonum multiflorum is Polygonum multiflorum that has been steamed and dried nine times; and the yeast extract, cellulase and bromelain were all purchased from Nanning Dongheng Huadao Biotechnology Co., Ltd.

[0051] Example 1

[0052] A traditional Chinese medicine composition that clears blood vessels, dissolves blood spots, regulates the five internal organs, and prevents and treats arteriosclerosis and its associated coronary heart disease, hypertension, hyperlipidemia, hyperglycemia, hyperuricemia, diabetic gangrene.

[0053] The traditional Chinese medicine composition, by weight, consists of the following raw materials: 18 parts of wolfberry, 18 parts of fleeceflower root, 18 parts of epimedium, 18 parts of privet fruit, 24 parts of angelica, 36 parts of dodder seed, 27 parts of astragalus, 36 parts of polygonatum, 18 parts of salvia miltiorrhiza, 27 parts of hawthorn, 18 parts of jujube seed, 36 parts of chrysanthemum, and 18 parts of lycium bark.

[0054] The preparation method of the traditional Chinese medicine composition is as follows:

[0055] (1) Add 92% ethanol (by volume) to Salvia miltiorrhiza, Polygonatum sibiricum and Polygonum multiflorum at a mass ratio of 1:10, sonicate at 45°C (400W) for 20 min, filter, and obtain ethanol extract and residue.

[0056] (2) Add water to wolfberry, epimedium, privet fruit, angelica, dodder seed, astragalus, hawthorn, jujube seed, chrysanthemum and lycium bark at a mass ratio of 1:12 and decoct once for 1 hour to obtain water extract.

[0057] (3) Mix the dregs and water extract, cool to 52°C, add enzyme and react for 3 hours, filter to obtain enzymatic hydrolysate;

[0058] The enzymes are yeast extractase, cellulase, and bromelain, and the mass ratio of the yeast extractase, cellulase, and bromelain is 0.8:1:0.2.

[0059] The amount of enzyme added is 0.5% of the water extract mass.

[0060] (4) Mix the alcohol extract and the enzyme hydrolysate and dry under reduced pressure (50℃, 0.05MPa) to obtain the final product.

[0061] Example 2

[0062] A traditional Chinese medicine composition that clears blood vessels, dissolves blood spots, regulates the five internal organs, and prevents and treats arteriosclerosis and its associated coronary heart disease, hypertension, hyperlipidemia, hyperglycemia, hyperuricemia, diabetic gangrene.

[0063] The traditional Chinese medicine composition, by weight, consists of the following raw materials: 18 parts of wolfberry, 18 parts of fleeceflower root, 18 parts of epimedium, 18 parts of privet fruit, 24 parts of angelica, 36 parts of dodder seed, 27 parts of astragalus, 36 parts of polygonatum, 18 parts of salvia miltiorrhiza, 27 parts of hawthorn, 18 parts of jujube seed, 36 parts of chrysanthemum, and 18 parts of lycium bark.

[0064] The preparation method of the traditional Chinese medicine composition is as follows:

[0065] (1) Add 90% ethanol (by volume) to Salvia miltiorrhiza, Polygonatum sibiricum and Polygonum multiflorum at a material-to-liquid ratio of 1:8, sonicate at 40°C (300W) for 30 min, filter, and obtain ethanol extract and residue.

[0066] (2) Add water to wolfberry, epimedium, privet fruit, angelica, dodder seed, astragalus, hawthorn, jujube seed, chrysanthemum and lycium bark at a mass ratio of 1:15 and decoct once for 2 hours to obtain water extract.

[0067] (3) Mix the dregs and water extract, cool to 50°C, add enzyme and react for 6 hours, filter to obtain enzymatic hydrolysate;

[0068] The enzymes are yeast extractase, cellulase and bromelain, and the mass ratio of yeast extractase, cellulase and bromelain is 0.5:1:0.1.

[0069] The amount of enzyme added is 0.3% of the water extract mass.

[0070] (4) Mix the alcohol extract and the enzyme hydrolysate and dry under reduced pressure (50℃, 0.05MPa) to obtain the final product.

[0071] Example 3

[0072] A traditional Chinese medicine composition that clears blood vessels, dissolves blood spots, regulates the five internal organs, and prevents and treats arteriosclerosis and its associated coronary heart disease, hypertension, hyperlipidemia, hyperglycemia, hyperuricemia, diabetic gangrene.

[0073] The traditional Chinese medicine composition, by weight, consists of the following raw materials: 18 parts of wolfberry, 18 parts of fleeceflower root, 18 parts of epimedium, 18 parts of privet fruit, 24 parts of angelica, 36 parts of dodder seed, 27 parts of astragalus, 36 parts of polygonatum, 18 parts of salvia miltiorrhiza, 27 parts of hawthorn, 18 parts of jujube seed, 36 parts of chrysanthemum, and 18 parts of lycium bark.

[0074] The preparation method of the traditional Chinese medicine composition is as follows:

[0075] (1) Add 90% ethanol (by volume) to Salvia miltiorrhiza, Polygonatum sibiricum and Polygonum multiflorum at a mass ratio of 1:15, sonicate at 40°C (300W) for 30 min, filter, and obtain ethanol extract and residue.

[0076] (2) Add water to wolfberry, epimedium, privet fruit, angelica, dodder seed, astragalus, hawthorn, jujube seed, chrysanthemum and lycium bark at a mass ratio of 1:10 and decoct once for 0.5 hours to obtain water extract;

[0077] (3) Mix the dregs and water extract, cool to 55°C, add enzyme and react for 2 hours, filter to obtain enzymatic hydrolysate;

[0078] The enzymes are yeast extractase, cellulase and bromelain, and the mass ratio of yeast extractase, cellulase and bromelain is 1:1:0.3.

[0079] The amount of enzyme added is 1.0% of the water extract mass.

[0080] (4) Mix the alcohol extract and the enzyme hydrolysate and dry under reduced pressure (50℃, 0.05MPa) to obtain the final product.

[0081] Comparative Example 1

[0082] A traditional Chinese medicine composition that clears blood vessels, dissolves blood spots, regulates the five internal organs, and prevents and treats arteriosclerosis and its associated coronary heart disease, hypertension, hyperlipidemia, hyperglycemia, hyperuricemia, diabetic gangrene.

[0083] The traditional Chinese medicine composition, by weight, consists of the following raw materials: 18 parts of wolfberry, 18 parts of fleeceflower root, 18 parts of epimedium, 18 parts of privet fruit, 24 parts of angelica, 36 parts of dodder seed, 27 parts of astragalus, 36 parts of polygonatum, 18 parts of salvia miltiorrhiza, 27 parts of hawthorn, 18 parts of jujube seed, 36 parts of chrysanthemum, and 18 parts of lycium bark.

[0084] The preparation method of the traditional Chinese medicine composition is as follows:

[0085] (1) Add water to the following ingredients at a mass ratio of 1:12: white salvia miltiorrhiza, polygonatum sibiricum, he shou wu, wolfberry, epimedium, privet fruit, angelica sinensis, dodder seed, astragalus membranaceus, hawthorn, jujube seed, chrysanthemum and lycium bark, decoct once for 1 hour, and obtain water extract.

[0086] (2) Mix the water extracts, cool to 52°C, add enzyme and react for 3 hours, filter to obtain the enzymatic hydrolysate;

[0087] The enzymes are yeast extractase, cellulase, and bromelain, and the mass ratio of the yeast extractase, cellulase, and bromelain is 0.8:1:0.2.

[0088] The amount of enzyme added is 0.5% of the water extract mass.

[0089] (3) Mix the enzyme hydrolysate and dry under reduced pressure (50℃, 0.05MPa) to obtain the final product.

[0090] Comparative Example 2

[0091] A traditional Chinese medicine composition that clears blood vessels, dissolves blood spots, regulates the five internal organs, and prevents and treats arteriosclerosis and its associated coronary heart disease, hypertension, hyperlipidemia, hyperglycemia, hyperuricemia, diabetic gangrene.

[0092] The traditional Chinese medicine composition, by weight, consists of the following raw materials: 18 parts of wolfberry, 18 parts of fleeceflower root, 18 parts of epimedium, 18 parts of privet fruit, 24 parts of angelica, 36 parts of dodder seed, 27 parts of astragalus, 36 parts of polygonatum, 18 parts of salvia miltiorrhiza, 27 parts of hawthorn, 18 parts of jujube seed, 36 parts of chrysanthemum, and 18 parts of lycium bark.

[0093] The preparation method of the traditional Chinese medicine composition is as follows:

[0094] (1) Add 92% ethanol (by volume) to Salvia miltiorrhiza, Ligustrum lucidum, Polygonatum sibiricum and Polygonum multiflorum at a mass ratio of 1:10, sonicate at 45°C (400W) for 20 min, filter, and obtain ethanol extract and residue.

[0095] (2) Add water to wolfberry, epimedium, angelica, dodder seed, astragalus, hawthorn, jujube seed, chrysanthemum and lycium bark at a mass ratio of 1:12 and decoct once for 1 hour to obtain water extract;

[0096] (3) Mix the dregs and water extract, cool to 52°C, add enzyme and react for 3 hours, filter to obtain enzymatic hydrolysate;

[0097] The enzymes are yeast extractase, cellulase and bromelain, and the mass ratio of yeast extractase, cellulase and bromelain is 0.1:1:1.

[0098] The amount of enzyme added is 0.5% of the water extract mass.

[0099] (4) Mix the alcohol extract and the enzyme hydrolysate and dry under reduced pressure (50℃, 0.05MPa) to obtain the final product.

[0100] Comparative Example 3

[0101] The difference between this comparative example and Example 1 is that the traditional Chinese medicine composition is prepared using the preparation method of Example 1 in the specification of Chinese Patent CN118806855A.

[0102] Example 1: Evaluation of the effect of improving microcirculation disorders

[0103] 1. Laboratory animals

[0104] SPF grade SD rats, male, weighing 220-240g.

[0105] 2. Drugs to be tested

[0106] The traditional Chinese medicine compositions prepared in Examples 1-3 and Comparative Examples 1-3.

[0107] 3. Experimental Methods

[0108] After one week of acclimatization, rats were randomly divided into a blank control group and an experimental group according to their body weight. A diabetes model was established in the experimental group using streptozotocin (STZ).

[0109] Specifically, after fasting for 12 hours, rats were given a single intraperitoneal injection of STZ 65 mg / Kg (concentration 1 wt%, dissolved in 0.1 mol / L citrate buffer, pH 4.5). One week later, blood glucose was measured by collecting blood from the tail vein. Rats with blood glucose values ​​greater than 12 mmol / ml and exhibiting polydipsia and polyuria were identified as diabetic model rats.

[0110] Diabetic rats were randomly divided into a model group, Example 1-Example 3 groups, and Comparative Example 1-Comparative Example 3 groups, with 8 rats in each group. Example 1-Example 3 groups and Comparative Example 1-Comparative Example 3 groups were administered the corresponding herbal composition by gavage at a daily dose of 2g crude drug / kg (dissolved in physiological saline). The blank control group and model group were administered an equal volume of physiological saline by gavage. This administration was continued for 4 weeks.

[0111] After the experiment, the gangrene status of the limbs of rats in each group was observed and recorded, and the scores were calculated according to the criteria in Table 1. The total score of each group of rats was calculated.

[0112] Rats were anesthetized by intraperitoneal injection of 3% sodium pentobarbital at a dose of 2 mL / kg. Blood was collected from the abdominal artery to detect hemorheological parameters and serum VEGF levels.

[0113] Table 1

[0114]

[0115] 4. Experimental Results

[0116] 4.1 Effect on improving diabetic foot symptoms

[0117] The gangrene scores of the limbs of rats in each group are shown in Table 2.

[0118] Table 2

[0119]

[0120] The results showed that no gangrene of the extremities was observed in any of the rat groups during the first week of the experiment. After two weeks, except for the blank control group, all rat groups developed varying degrees of gangrene of the extremities. At the end of the experiment, the number of rats with gangrene of the extremities in Examples 1-3 was significantly less than that in the model group and Comparative Examples 1-2. This indicates that the traditional Chinese medicine compositions prepared in Examples 1-3 of this invention can significantly improve the symptoms of gangrene of the extremities in diabetic foot.

[0121] 4.2 Improvement of the "three highs" phenomenon in the hemorheology of diabetes mellitus

[0122] The changes in hemorheology and serum VEGF levels (mean ± standard deviation) of rats in each group are shown in Table 3.

[0123] Table 3

[0124]

[0125] Note: In the same column, different letters indicate that the data between groups are significantly different, P < 0.05.

[0126] The results showed that, compared with the blank control group, the whole blood viscosity, blood viscosity, erythrocyte aggregation index, and serum VEGF levels in the model group rats were significantly increased (P < 0.05). Compared with the model group, the whole blood viscosity, blood viscosity, erythrocyte aggregation index, and serum VEGF levels in the Example 1-Example 3 groups rats were significantly decreased (P < 0.05), indicating that the traditional Chinese medicine composition provided in Examples 1-3 of this invention has a significant inhibitory effect on the "three highs" phenomenon in the hemorheology of diabetes (i.e., high blood viscosity, high platelet aggregation, and high capillary permeability), and can be used as a microcirculation-improving drug for the prevention and treatment of various diseases caused by microvascular circulation disorders.

[0127] Example 2: Summary of Clinical Treatment Cases

[0128] 1. Basic Information

[0129] General data were selected from inpatients and outpatients of the Department of Traditional Chinese Medicine at the First Affiliated Hospital of Fujian Medical University. The inclusion criteria for cases are as follows:

[0130] 1) Ultrasound diagnosis of carotid intima-media thickness (IMT) > 1.0 mm indicates plaque presence.

[0131] 2) Be able to adhere to taking medicine for 12 weeks and meet the conditions for clinical follow-up.

[0132] 3) Age between 50 and 75 years old.

[0133] 4) Different clinical manifestations according to different involved organs: Coronary heart disease, hypertension, hyperlipidemia, hyperglycemia, hyperuric acid gout or diabetic acromegaly caused by atherosclerosis.

[0134] Exclusion criteria for cases are as follows:

[0135] 1) Those with severe plaque in the lumen of the carotid artery detected by carotid ultrasound, resulting in blood flow blockage;

[0136] 2) Those with carotid IMT < 1.0mm3, combined with acute myocardial infarction, heart failure, or acute cerebrovascular disease.

[0137] A total of 80 patients meeting the above conditions were recruited and randomly divided into a treatment group and a positive control group according to the random number table method. There were no significant differences in general data such as age, course of disease, and condition between the two groups of patients (P > 0.05), and they were comparable.

[0138] There were 50 cases in the experimental group, including 30 males and 20 females; aged 45 - 78 years, among which 25 cases had coronary heart disease, 20 cases had hypertension, 18 cases had hyperlipidemia, 28 cases had hyperglycemia, 12 cases had hyperuric acid, and 10 cases had diabetic acromegaly;

[0139] There were 30 cases in the positive control group, including 16 males and 14 females, aged 45 - 75 years, among which 14 cases had coronary heart disease, patients with 12 cases had hypertension, 9 cases had hyperlipidemia, 16 cases had hyperglycemia, 8 cases had hyperuric acid, and 6 cases had diabetic acromegaly.

[0140] Treatment method: The treatment group was given the traditional Chinese medicine composition prepared in Example 1, 1.5 g each time, twice a day, morning and evening; the positive control group took the traditional Chinese medicine composition prepared in Comparative Example 3, 2 g each time, twice a day, morning and evening. The two groups of patients took the medicine continuously for 12 weeks. High-resolution ultrasound was used to non-invasively detect the structure of the carotid artery vascular wall, the morphology of plaques, and hemodynamics in patients with carotid atherosclerosis. A biochemical analyzer was used to detect total cholesterol (Tc), triglyceride (Tg), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), high-sensitivity C-reactive protein (hs-CRP), fibrinogen (Fib), blood glucose, and glycated hemoglobin (HbA1c). A diabetic foot nerve examination system was used to detect the degree of nerve injury and conduct relevant analysis.

[0141] Efficacy evaluation criteria:

[0142] Significant effect: Corresponding clinical symptoms are significantly reduced, complications are significantly improved, blood pressure, blood lipids, blood sugar, uric acid decrease, and nerve function is restored to near normal levels;

[0143] Effective: Corresponding clinical symptoms are alleviated, complications are slightly improved, blood pressure, blood lipids, blood sugar, uric acid decrease, and nerve function recovers within 20%;

[0144] Ineffective: Clinical symptoms and signs showed almost no improvement.

[0145] The results are shown in Table 4.

[0146] Table 4

[0147]

[0148] The results showed that, compared with the positive control group, the traditional Chinese medicine composition prepared in Example 1 of this invention has a more significant advantage in improving the treatment of diabetic gangrene of the extremities.

[0149] The above description, in conjunction with specific embodiments, further illustrates the present invention. However, these embodiments are merely exemplary and do not constitute any limitation on the scope of the present invention. Those skilled in the art should understand that modifications or substitutions to the details and form of the technical solutions of the present invention can be made without departing from the spirit and scope of the invention, and all such modifications and substitutions fall within the protection scope of the present invention.

Claims

1. A traditional Chinese medicine composition for the prevention and treatment of coronary heart disease, hypertension, hyperlipidemia, hyperglycemia, hyperuricemia, and diabetic gangrene of the extremities, characterized in that, Made from the following ingredients by weight: 15-20 parts of wolfberry, 15-20 parts of fleeceflower root, 15-20 parts of epimedium, 15-20 parts of privet fruit, 22-26 parts of angelica root, 34-38 parts of dodder seed, 25-30 parts of astragalus root, 34-38 parts of polygonatum rhizome, 15-20 parts of salvia root, 25-30 parts of hawthorn fruit, 15-20 parts of jujube seed, 34-38 parts of chrysanthemum flower, and 15-20 parts of lycium root bark; The preparation method of the traditional Chinese medicine composition includes the following steps: (1) White-flowered Salvia miltiorrhiza, Polygonatum sibiricum and Polygonum multiflorum were subjected to ultrasonic treatment with alcohol, and solid-liquid separation was performed to obtain alcohol extract and residue; (2) Extract the following ingredients with water: wolfberry, epimedium, privet fruit, angelica, dodder seed, astragalus, hawthorn, jujube seed, chrysanthemum and lycium bark to obtain water extract; (3) Mix the dregs and water extracts together for enzymatic hydrolysis, and separate the solid and liquid components to obtain the hydrolysate; (4) Mix the alcohol extract and the enzyme hydrolysate, and dry to obtain the final product; The alcohol mentioned in step (1) is ethanol with a volume fraction of 90%-95%; The enzymes used in the enzymatic hydrolysis in step (3) are yeast extractase, cellulase and bromelain, and the mass ratio of yeast extractase, cellulase and bromelain is 0.5-1:1:0.1-0.

3. The amount of enzyme added in step (3) is 0.3%-1% of the water extract.

2. The traditional Chinese medicine composition according to claim 1, characterized in that, The ultrasonic treatment in step (1) is as follows: temperature 40℃-50℃, power 300 W-500W, time 15 min-30 min.

3. The traditional Chinese medicine composition according to claim 1, characterized in that, The water extraction in step (2) involves boiling in water, and the water extraction is performed 1-3 times, with each extraction lasting 0.5 h-2 h.

4. The traditional Chinese medicine composition according to claim 1, characterized in that, The mass ratio of yeast extractase, cellulase and bromelain in step (3) is 0.8:1:0.2; And / or the enzymatic hydrolysis temperature in step (3) is 50℃-55℃, the enzymatic hydrolysis time is 2h-6h, and the pH of the enzymatic hydrolysis is 5.5-6.

5.

5. The traditional Chinese medicine composition according to claim 1, characterized in that, The Polygonatum sibiricum is prepared by steaming and drying nine times; the Polygonum multiflorum is prepared by steaming and drying nine times.

6. The use of the traditional Chinese medicine composition according to any one of claims 1-5 in the preparation of a medicament for improving microcirculation disorders, characterized in that, The microcirculatory disturbance is diabetic gangrene of the extremities.

7. The use of the traditional Chinese medicine composition according to any one of claims 1-5 in the preparation of a medicament for the prevention and treatment of coronary heart disease, hypertension, hyperlipidemia, hyperglycemia, hyperuricemia and diabetic gangrene.

8. A pharmaceutical preparation, characterized in that, It includes the traditional Chinese medicine composition according to any one of claims 1-5 and pharmaceutically acceptable excipients.

9. The pharmaceutical preparation according to claim 8, characterized in that, The dosage form of the pharmaceutical preparation is tablets, granules, capsules, pills, powders, syrups, or mixtures.

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