Composition for improving diabetes accompanied by cerebrovascular diseases as well as preparation method and application of composition

Abstract

The invention provides a composition for improving diabetes with cerebrovascular diseases and a preparation method and application thereof, and relates to the technical field of traditional Chinese medicines. The composition is prepared from the following raw materials in parts by weight: 100 to 150 parts of radix puerariae, 20 to 40 parts of radix angelicae sinensis, 30 to 50 parts of radix paeoniae rubra, 15 to 25 parts of rhizoma chuanxiong, 10 to 20 parts of rhizoma pinellinae praeparata, 8 to 13 parts of radix glycyrrhizae preparata, 15 to 26 parts of radix asparagi, 30 to 50 parts of rhizoma coptidis and 15 to 27 parts of pericarpium trichosanthis. The radix puerariae, the radix angelicae sinensis, the rhizoma coptidis and the pericarpium trichosanthis are extracted with ethanol, medicine residues are decocted with other components, and the obtained composition has the effect of improving the symptoms of diabetes with cerebrovascular diseases and can reduce the blood sugar level and the content of inflammatory factors; the blood mobility is obviously improved, and the recognition capability on new things is improved; the sleep latency period and the average respiratory rate are reduced, and the symptoms of dizziness, palpitation, annoyance and dizziness in chest and hypochondrium fullness are improved. The composition is applied to preparation of drugs for improving diabetes with cerebrovascular diseases, and the effect is remarkable.

Description

Technical Field

[0001] This invention belongs to the field of traditional Chinese medicine technology, specifically relating to compositions for improving diabetes mellitus accompanied by cerebrovascular disease, their preparation methods, and applications. Background Technology

[0002] The risk of cerebrovascular disease is higher in diabetic patients than in non-diabetic individuals, and the core causes are closely related to vascular damage, metabolic disorders, and the accumulation of multiple risk factors caused by diabetes. Long-term hyperglycemia in diabetic patients damages vascular endothelial cells, leading to atherosclerosis. Hyperglycemia, through oxidative stress, inflammatory responses, and abnormal lipid metabolism (low-density lipoprotein cholesterol deposition), causes narrowing of cerebral blood vessels, thrombosis, and ultimately cerebral infarction. Long-term hypertension (a common complication of diabetes) increases cerebral vascular pressure and accelerates arteriosclerosis; furthermore, diabetic nephropathy leading to renal insufficiency can cause water and sodium retention, further affecting cerebral blood flow; diabetes is often accompanied by elevated triglycerides, decreased high-density lipoprotein, and dyslipidemia, causing atherosclerosis.

[0003] Treatment methods for diabetes mellitus accompanied by cerebrovascular disease generally include: blood glucose control, cerebrovascular disease treatment, blood glucose stabilization, and blood lipid reduction. Chinese invention patent CN114652809A discloses a combination preparation for the prevention and treatment of type 2 diabetes mellitus with cardiovascular and cerebrovascular diseases. It consists of a liquid preparation and a powder preparation. The liquid preparation includes the following ingredients in parts by weight: 30-40 parts fish oil, 20-30 parts krill oil, and 20-30 parts Acer truncatum seed oil. The powder preparation includes the following ingredients in parts by weight: 30-40 parts wheat oligopeptides, 30-40 parts Haematococcus pluvialis, and 10-20 parts bamboo leaf flavonoids. This combination preparation of the invention provides bidirectional regulation of blood lipids. When lipid metabolism disorders occur, this combination preparation can lower low-density lipoprotein while raising high-density lipoprotein; lower inflammatory factors while raising anti-inflammatory factors; and lower fasting blood glucose.

[0004] However, most current research is limited to single symptoms, with limited studies on complex conditions of diabetes accompanied by cerebrovascular disease. For example, Chinese invention patent CN120361129A discloses a traditional Chinese medicine composition for treating metabolic disorders of glucose and lipids. The raw materials, by weight, include: 15-19 parts of Coptis chinensis, 10-15 parts of Rhodiola rosea, 10-20 parts of Gynostemma pentaphyllum, 9-12 parts of Bombax ceiba, 10-15 parts of Sapindus mukorossi, 9-15 parts of Salvia miltiorrhiza, 10-15 parts of Alisma plantago-aquatica, 9-12 parts of Artemisia capillaris, 9-12 parts of Bupleurum chinense, 5-10 parts of Cassia tora, 10-15 parts of Anemarrhena asphodeloides, 10-15 parts of Crataegus pinnatifida, 6-9 parts of Polygonum cuspidatum, and 5-10 parts of Citrus aurantium. Although this traditional Chinese medicine composition reduces the risk of type 2 diabetes, it has not shown significant therapeutic effects on related symptoms of cerebrovascular disease, such as liver qi stagnation and upward rushing of heat.

[0005] Current technology indicates that kudzu root and plum root bark (often replaced by mulberry bark), combined with bupleurum and scutellaria, can both soothe the liver and clear heat, and alleviate symptoms such as irritability, anger, frequent sighing, and chest and rib distension caused by liver qi stagnation. It is particularly suitable for symptoms of "running piglet qi" induced or aggravated by emotional stimulation. Scutellaria and rehmannia clear heat and cool the blood, combined with pinellia and ginger to harmonize the stomach and relieve nausea, effectively alleviating symptoms such as bitter taste in the mouth, dry throat, and irritability caused by liver qi stagnation transforming into heat, or by a combination of cold and heat. Angelica and chuanxiong nourish and invigorate the blood, while peony and licorice relieve spasms and pain, showing some therapeutic effect on cerebrovascular diseases. However, there is still room for improvement in the effects of the above traditional formulas on improving diabetes, palpitations, and irritability.

[0006] Therefore, it is necessary to find new traditional Chinese medicine formulas that are effective in improving diabetes mellitus complicated with cerebrovascular disease, so as to improve the treatment effect on the above-mentioned related complex symptoms and improve patients' treatment compliance. Summary of the Invention

[0007] This invention addresses the problems existing in the prior art by providing a composition for improving diabetes mellitus complicated with cerebrovascular disease, its preparation method, and its application. Nine components, namely kudzu root, angelica, red peony root, chuanxiong rhizome, prepared pinellia tuber, prepared licorice root, asparagus root, coptis root, and trichosanthes peel, interact and are rationally combined to bring about significant improvement in the combined symptoms of diabetes mellitus complicated with cerebrovascular disease.

[0008] To achieve the above objectives, the technical solution adopted by the present invention is as follows: First, the present invention provides a composition for improving diabetes mellitus accompanied by cerebrovascular disease, the raw materials of which include: kudzu root, angelica, red peony root, chuanxiong rhizome, prepared pinellia tuber, prepared licorice root, asparagus root, coptis root, and trichosanthes peel.

[0009] Preferably, the composition comprises, by weight, the following raw materials: 100-150 parts of kudzu root, 20-40 parts of angelica root, 30-50 parts of red peony root, 15-25 parts of chuanxiong rhizome, 10-20 parts of prepared pinellia tuber, 8-13 parts of prepared licorice root, 15-26 parts of asparagus root, 30-50 parts of coptis root, and 15-27 parts of trichosanthes peel.

[0010] More preferably, the composition, by weight, comprises the following raw materials: 110-130 parts of kudzu root, 25-35 parts of angelica root, 35-45 parts of red peony root, 18-22 parts of chuanxiong rhizome, 13-18 parts of prepared pinellia tuber, 9-11 parts of prepared licorice root, 18-22 parts of asparagus root, 35-45 parts of coptis root, and 18-23 parts of trichosanthes peel.

[0011] More preferably, the composition, by weight, comprises the following raw materials: 120 parts of kudzu root, 30 parts of angelica root, 40 parts of red peony root, 20 parts of chuanxiong rhizome, 15 parts of prepared pinellia tuber, 10 parts of prepared licorice root, 20 parts of asparagus root, 40 parts of coptis root, and 20 parts of trichosanthes peel.

[0012] Then, the present invention provides a method for preparing the above composition, comprising the steps of: (1) Pueraria lobata, Angelica sinensis, Coptis chinensis and Trichosanthes kirilowii peel were extracted by ethanol reflux, filtered, and the filtrate A and the residue were recovered; (2) Mix the dregs from step (1) with red peony root, chuanxiong rhizome, prepared pinellia tuber, prepared licorice root, and asparagus root, decoct, filter, and recover filtrate B; (3) Combine filtrate A and filtrate B to obtain the composition.

[0013] Preferably, in step (1), the reflux extraction is performed with an ethanol volume concentration of 35%-60%, reflux extraction at 45-65℃ for 2-4 hours, and an extraction solid-liquid ratio of 1g:20-30mL.

[0014] More preferably, in step (1), the reflux extraction uses an ethanol volume concentration of 50%.

[0015] More preferably, in step (1), the reflux extraction is performed at 55°C for 3 hours.

[0016] More preferably, in step (1), the reflux extraction has a solid-liquid ratio of 1g:25mL. Preferably, in step (1), the filtrate A needs to be treated with reduced pressure to remove ethanol before merging.

[0017] Preferably, in step (2), the decoction is specifically: boiling and decocting 2-4 times, each time for 1-3 hours; based on the quality of all Chinese herbal raw materials, the solid-liquid ratio of the decoction is 1g:20-30mL.

[0018] More preferably, in step (2), the decocting specifically involves boiling and decocting three times, each time for 2 hours.

[0019] More preferably, in step (2), the solid-liquid ratio of the decoction is 1g:25mL.

[0020] Preferably, in step (3), the composition can be a liquid, a paste, or a solid; when it is a liquid, the filtrate can be concentrated or not; when it is a paste, the filtrate needs to be concentrated; when it is a solid, the filtrate needs to be concentrated and dried to obtain the composition.

[0021] Furthermore, the present invention provides the use of the above composition in the preparation of a medicament for improving diabetes mellitus with cerebrovascular disease.

[0022] In this invention, the diabetes in the application specifically refers to type 2 diabetes.

[0023] In this invention, the cerebrovascular disease in the application includes, but is not limited to: decreased cerebral blood flow velocity, reduced cerebral blood flow, decreased ability to recognize new objects and memory, high inflammation, high blood pressure, dizziness, palpitations, shortness of breath, irritability, increased appetite, difficulty falling asleep, and rapid and frequent breathing.

[0024] Finally, the present invention provides a medicament for improving diabetes mellitus with cerebrovascular disease, comprising the following components: the above-described composition.

[0025] Preferably, the drug may further include a drug carrier. The drug carrier may be solid or liquid. Examples of solid carriers include lactose, kaolin, sucrose, talc, gelatin, agar, pectin, gum arabic, magnesium stearate, and stearic acid. Examples of liquid carriers include syrup, peanut oil, olive oil, and water.

[0026] In preparing compositions for oral dosage forms, any convenient pharmaceutical medium can be used. For example, water, ethanol, oils, alcohols, flavoring agents, preservatives, coloring agents, etc., can be used to form oral liquid dosage forms, such as suspensions and solutions; while carriers, such as starch, sugars, microcrystalline cellulose, diluents, granulators, emulsifiers, lubricants, binders, and disintegrants, can be used to form oral solid dosage forms, such as powders, capsules, and tablets. Tablets and capsules are preferred oral dosage units using solid pharmaceutical carriers due to their ease of administration. Tablets can be coated using standard aqueous or non-aqueous techniques.

[0027] Tablets containing the herbal composition or extract of the present invention can be prepared by compression or molding, optionally using one or more excipients or adjuvants. The active ingredient can be compressed in a free-flowing form (e.g., powder or granules) in a suitable machine, optionally mixed with binders, lubricants, inert diluents, surfactants, or dispersants. Molded tablets can be molded in a suitable machine, i.e., a mixture of powdered compounds moistened with an inert liquid diluent. Each tablet preferably contains about 0.05 mg to about 5 g of active ingredient, and each sachet or capsule preferably contains about 0.05 mg to about 5 g of active ingredient. For example, a formulation intended for oral administration to humans may contain about 0.5 mg to about 5 g of active pharmaceutical ingredient, mixed with a suitable and convenient carrier material, which may comprise about 5% to 95% of the total composition. Unit dosage forms typically contain about 1 mg to about 2 g of active ingredient, typically in doses of 25 mg, 50 mg, 100 mg, 200 mg, 300 mg, 400 mg, 500 mg, 600 mg, 800 mg, or 1000 mg.

[0028] In addition to the carrier components described above, the pharmaceutical formulations may include (if applicable) one or more additional carrier components, such as diluents, buffers, flavoring agents, binders, surfactants, thickeners, lubricants, preservatives (including antioxidants), etc. Furthermore, other excipients may be added, such as lactose, starch, cellulose derivatives, magnesium stearate, stearic acid, etc., colorants, and flavoring agents, etc., to make the formulation isotonic with the blood of the intended receptor. Components containing the traditional Chinese medicine composition of this invention can also be prepared in powder or concentrated form.

[0029] Preferably, the dosage form of the drug is not limited to pills, capsules, granules, oral liquids, powders, tablets, lozenges, ointments, etc., and a suitable drug carrier in the art can be selected for different dosage forms.

[0030] In this invention, the composition for improving diabetes mellitus with cerebrovascular disease comprises the following ingredients: kudzu root, angelica root, red peony root, chuanxiong rhizome, prepared pinellia tuber, prepared licorice root, asparagus root, coptis root, and trichosanthes peel.

[0031] Kudzu root: Rich in flavonoids, mainly containing puerarin, daidzein, and daidzein. Puerarin can regulate the insulin signaling pathway, protect pancreatic β cells, improve insulin resistance in patients with type 2 diabetes, lower blood sugar levels, inhibit the release of inflammatory factors, and also has a certain protective effect on nerves.

[0032] Angelica sinensis contains various volatile oils and water-soluble components. Among them, ferulic acid has multiple activities such as anti-oxidation, anti-thrombosis, and immune regulation, and has a protective effect on blood vessels. Angelica sinensis can reduce the breakdown of liver glycogen into glucose by inhibiting the activity of glycogen phosphorylase in the liver, thereby reducing fasting blood glucose. Angelica sinensis can clear a large number of free radicals generated after cerebral ischemia, inhibit inflammatory responses (such as reducing NF-κB activation), and reduce oxidative stress and inflammatory damage to nerve cells.

[0033] Red peony root contains active ingredients such as paeoniflorin, paeoniflorin lactone, and gallic acid, which have anti-inflammatory, antioxidant, vascular and nerve cell protective, and cerebral blood flow increasing effects. Red peony root also regulates blood sugar, improves insulin function, and reduces tissue damage, thereby improving diabetic complications.

[0034] Chuanxiong (Ligusticum striatum): As a commonly used blood-activating and stasis-removing drug, it has significant anti-thrombotic, microcirculation-improving, and vascular endothelial-protective effects. It can also inhibit the release of inflammatory factors (such as TNF-α and IL-6), reduce the interference of inflammation on the insulin signaling pathway, improve cell sensitivity to insulin, and help improve insulin resistance in patients with type 2 diabetes. Studies have shown that chuanxiongqin can reduce cerebral vascular permeability, reduce fluid infiltration into brain tissue, and alleviate the degree of cerebral edema.

[0035] Processed Pinellia: This is a commonly used Chinese medicine made from processed Pinellia. It has a mild medicinal property and its main functions are to dry dampness, resolve phlegm, and relieve nausea and vomiting.

[0036] Prepared licorice root: This is a processed product of licorice root that has been processed with honey. It has a mild medicinal property, enhanced effects of tonifying the middle and replenishing qi, and retains the core active ingredients of licorice root. Licorice polysaccharides also have the effects of reducing blood viscosity, improving blood flow, and helping to prevent cerebral infarction.

[0037] Asparagus: It has the effect of nourishing yin and can tonify the kidney and moisten dryness in traditional Chinese medicine theory. The polysaccharide components in asparagus can inhibit the expression of renal fibrosis-related proteins (such as TGF-β1) and reduce urinary protein excretion, which is especially suitable for diabetic nephropathy patients with yin deficiency.

[0038] Coptis chinensis is a commonly used herb in Traditional Chinese Medicine for clearing heat, drying dampness, purging fire, and detoxifying. Berberine is the most abundant active ingredient in Coptis chinensis, accounting for about 50%-80% of the total alkaloids. Coptis chinensis can reduce the damage to cerebral blood vessels caused by blood pressure fluctuations and has anti-thrombotic effects. Berberine can also lower total cholesterol, triglycerides, and low-density lipoprotein (LDL), while raising high-density lipoprotein (HDL) and reducing the risk of atherosclerosis.

[0039] Trichosanthes peel: The dried pericarp of the Trichosanthes fruit (Trichosanthes kirilowii), a plant in the Cucurbitaceae family, is a commonly used phlegm-resolving and chest-relieving herb in Traditional Chinese Medicine. Trichosanthes saponins are triterpenoid saponins unique to Trichosanthes peel, possessing expectorant, lipid-regulating, and vascular-protective effects. Trichosanthes peel is also rich in flavonoids, which help regulate blood sugar and insulin function. Diabetes is often accompanied by hyperlipidemia (a manifestation of "phlegm turbidity" in Traditional Chinese Medicine theory). The "phlegm-resolving" effect of Trichosanthes peel corresponds to its lipid-regulating effect in modern pharmacology: triterpenoid saponins and flavonoids can lower serum total cholesterol, triglycerides, and low-density lipoprotein (LDL), while increasing high-density lipoprotein (HDL), reducing the risk of atherosclerosis and thus lowering the incidence of macrovascular complications of diabetes (such as coronary heart disease and cerebrovascular disease). Triterpenoid saponins and flavonoids also have certain anti-inflammatory activity, inhibiting the activation of inflammatory factors after cerebral ischemia and reducing neuroinflammatory responses.

[0040] In the composition of this invention, kudzu root is the principal ingredient, which is sweet and pungent in taste and cool in nature. It enters the spleen and stomach meridians; its functions include relieving muscle tension and reducing fever, promoting body fluid production and quenching thirst, raising yang and stopping diarrhea, and promoting blood circulation and removing blood stasis.

[0041] Assistant herbs: Coptis chinensis and Paeonia lactiflora. Coptis chinensis is extremely bitter and cold in nature, entering the heart, spleen, stomach, gallbladder, and large intestine meridians. It excels at clearing heat and drying dampness, purging fire and detoxifying. Used in large quantities as an assistant herb, its extremely cold nature effectively clears the excess fire and damp heat in the upper and middle jiao, directly dispelling the fire toxins carried in stagnant qi. It is a key herb targeting the pathogenesis of "heat accumulation." Paeonia lactiflora is bitter and slightly cold in nature, entering the liver meridian. It excels at clearing heat and cooling blood, dispersing blood stasis and relieving pain. When used in equal amounts with Coptis chinensis, it focuses on entering the blood level, activating blood circulation and dispersing blood stasis, effectively breaking up the stagnation of qi and blood, and unblocking the meridians to relieve pain. Its cold nature also helps Coptis chinensis clear heat from the blood level. One treats heat toxins in the qi level, and the other treats blood stasis and heat; they complement each other and serve as assistant herbs.

[0042] The adjuvant herbs are: Pinellia ternata (processed), Trichosanthes kirilowii peel, Angelica sinensis, Ligusticum chuanxiong, and Asparagus cochinchinensis. Among them, Pinellia ternata is pungent and warm, drying dampness, resolving phlegm, and relieving nausea and vomiting; Trichosanthes kirilowii peel is sweet and cold, clearing heat, resolving phlegm, and promoting qi circulation and chest tightness. Pinellia ternata and Trichosanthes kirilowii peel form a combination for resolving phlegm and dispersing nodules. The "pungent and dispersing" properties of Pinellia ternata and the "sweet and moistening" properties of Trichosanthes kirilowii peel complement each other, working together to clear phlegm, relieve chest tightness, and disperse stagnant qi, specifically targeting the accompanying symptoms of "phlegm accumulation," thus removing obstacles to the downward flow of qi.

[0043] Angelica sinensis is sweet, pungent, and warm, and nourishes and invigorates blood; Ligusticum chuanxiong is pungent and warm, and invigorates blood, promotes qi circulation, dispels wind, and relieves pain. Angelica sinensis and Ligusticum chuanxiong are the core of "nourishing and invigorating blood". The two nourish yin blood, promote blood circulation, and prevent cold and dampness from accumulating and phlegm and blood stasis from forming. This reflects the idea of ​​"treating wind by first treating blood, and wind will disappear when blood circulates" and treating qi and blood at the same time.

[0044] Asparagus root is sweet and bitter in taste, and cold in nature; it enters the lung and kidney meridians; its function is to nourish yin and moisten dryness, clear the lungs and generate fluids. Among the bitter, cold, and drying, and pungent and warm dispersing herbs in the whole formula, asparagus root, as an "assistant herb," ​​can prevent the other herbs from damaging the yin fluids due to its sweet and cold yin-nourishing effect.

[0045] The guiding herb is prepared licorice root. Prepared licorice root is sweet in taste and neutral in nature; it enters the heart, lung, spleen, and stomach meridians; it excels at tonifying the spleen and stomach, replenishing qi and restoring the pulse, and harmonizing the effects of other herbs. It is used in the lightest dosage and is ranked as the guiding herb.

[0046] The composition of this invention uses kudzu root as the principal ingredient, in a single, large quantity, to promote the upward movement of clear yang, relax muscles and tendons, and unblock the meridians. It acts as the pivot of qi, guiding the entire formula to clear stagnation and harmonize ascending and descending qi. Coptis chinensis and Paeonia lactiflora are used as assistant ingredients. Coptis chinensis, bitter and cold, directly suppresses the fire of the heart and stomach to clear heat and dry dampness; Paeonia lactiflora, cooling and dispersing, invigorates blood and removes blood stasis to unblock the meridians and relieve pain. Together, they clear away stagnant heat and phlegm, assisting the principal ingredient in eliminating the core pathogenic factor. Pinellia ternata and Trichosanthes kirilowii peel are added as adjuvants to resolve phlegm and dissipate nodules, relieve chest tightness and lower qi, specifically targeting phlegm obstruction. Angelica sinensis combined with Ligusticum chuanxiong nourishes blood, invigorates blood, promotes qi circulation and relieves pain, addressing both qi and blood simultaneously. Asparagus cochinchinensis nourishes yin and moistens dryness, clears heat and reduces fire, and counteracts the pungent, dry, bitter, and cold properties of the other ingredients. Glycyrrhiza uralensis is used as the guiding ingredient to harmonize the other ingredients, tonify qi and harmonize the middle jiao, and coordinate the overall effect. The combined effects of these herbs promote the upward movement of clear yang and descending of turbid yang, clear heat and resolve phlegm, invigorate blood and dissipate nodules.

[0047] Compared with the prior art, the present invention has the following beneficial effects: 1. Through in-depth research on the components of the composition, this invention has discovered that the nine components—Pueraria lobata, Angelica sinensis, Paeonia lactiflora, Ligusticum chuanxiong, Pinellia ternata, Glycyrrhiza uralensis, Asparagus cochinchinensis, Coptis chinensis, and Trichosanthes kirilowii peel—interact and are rationally combined to significantly improve the combined symptoms of diabetes mellitus accompanied by cerebrovascular disease. The composition of this invention can significantly reduce sleep latency and average respiratory rate, improve clinical symptoms of dizziness, palpitations, and chest and rib distension caused by "running piglet qi" (a traditional Chinese medicine concept); significantly reduce blood glucose levels and the content of inflammatory factors; regulate blood lipid levels; significantly improve blood fluidity; and enhance the ability to recognize new things.

[0048] 2. The composition of the present invention has a clear formulation and a simple preparation method. First, kudzu root, angelica, coptis and trichosanthes peel are extracted with ethanol. Then, the residue and the remaining Chinese medicine components are decocted. The resulting composition is rich in flavonoids, berberine, puerarin and other components. The interaction of these components brings about a significant improvement in the symptoms of diabetes with cerebrovascular disease, and can effectively improve palpitations, irritability and improve sleep quality. Detailed Implementation

[0049] The following non-limiting embodiments are intended to enable those skilled in the art to gain a more comprehensive understanding of the present invention, but do not limit the invention in any way. The following content is merely an exemplary description of the scope of protection claimed by the present invention, and those skilled in the art can make various changes and modifications to the present invention based on the disclosed content, and such changes should also fall within the scope of protection claimed by the present invention.

[0050] When numerical ranges are given in the embodiments, it should be understood that, unless otherwise stated in the invention, both endpoints of each numerical range and any value between the two endpoints may be selected. 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.

[0051] The present invention will be further described below by way of specific embodiments. Unless otherwise specified, all chemical reagents used in the embodiments of the present invention are obtained through conventional commercial channels. Products from different manufacturers do not have a significant impact on the effectiveness.

[0052] Basic Implementation A composition for improving diabetes mellitus accompanied by cerebrovascular disease, comprising the following raw materials by weight: 100-150 parts of kudzu root, 20-40 parts of angelica sinensis, 30-50 parts of red peony root, 15-25 parts of chuanxiong rhizome, 10-20 parts of prepared pinellia tuber, 8-13 parts of prepared licorice root, 15-26 parts of asparagus root, 30-50 parts of coptis root, and 15-27 parts of trichosanthes peel.

[0053] The method for preparing the composition is as follows: (1) Pueraria lobata, Angelica sinensis, Coptis chinensis and Trichosanthes kirilowii peel were extracted by reflux with ethanol of 35%-65% (v / v) for 2-4 hours at an extraction temperature of 45-65℃ and a solid-liquid ratio of 1g:10-20mL. The mixture was then filtered, and the filtrate A and the residue were recovered. (2) Mix the dregs from step (1) with red peony root, chuanxiong rhizome, prepared pinellia tuber, prepared licorice root, and asparagus root. Add 10-20 times the amount of water and boil for 2-4 times (add water appropriately according to the water absorption of the herbs to ensure that the decoction does not burn). Each decoction lasts for 1-3 hours. Filter and recover the filtrate B. (3) Combine filtrate A and filtrate B to obtain a composition; the composition may be a liquid, paste or solid.

[0054] When the composition is a liquid, the filtrate can be concentrated or not subjected to cold shrinkage; when the composition is a paste, the filtrate needs to be concentrated; when the composition is a solid, the filtrate needs to be concentrated and dried at a temperature below 60°C.

[0055] Within the scope of the technical solutions described in this invention, the aforementioned technical effects can be achieved and the aforementioned technical problems can be solved.

[0056] Example 1 A composition for improving diabetes mellitus with cerebrovascular disease, comprising the following raw materials by weight: 120 parts of kudzu root, 30 parts of angelica sinensis, 40 parts of red peony root, 20 parts of chuanxiong rhizome, 15 parts of prepared pinellia tuber, 10 parts of prepared licorice root, 20 parts of asparagus root, 40 parts of coptis root, and 20 parts of trichosanthes peel.

[0057] The method for preparing the composition is as follows: (1) Pueraria lobata, Angelica sinensis, Coptis chinensis and Trichosanthes kirilowii peel were extracted by reflux of 50% ethanol for 3 h at an extraction temperature of 55℃ and a solid-liquid ratio of 1 g: 25 mL. The mixture was filtered and the filtrate A and the residue were recovered. (2) Mix the dregs from step (1) with red peony root, chuanxiong rhizome, prepared pinellia tuber, prepared licorice root, and asparagus root. Add water equal to 25 times the weight of the Chinese herbs and boil for 2 hours each time. Filter, combine the filtrates, and recover filtrate B. (3) Combine filtrate A and filtrate B, concentrate, freeze dry to obtain the composition.

[0058] Example 2 A composition for improving diabetes mellitus with cerebrovascular disease, comprising the following raw materials by weight: 110 parts of kudzu root, 25 parts of angelica sinensis, 35 parts of red peony root, 18 parts of chuanxiong rhizome, 13 parts of prepared pinellia tuber, 9 parts of prepared licorice root, 18 parts of asparagus root, 35 parts of coptis root, and 18 parts of trichosanthes peel.

[0059] The method for preparing the composition is as follows: (1) Pueraria lobata, Angelica sinensis, Coptis chinensis and Trichosanthes kirilowii peel were extracted by reflux of 35% ethanol for 4 h at an extraction temperature of 65℃ and a solid-liquid ratio of 1 g: 30 mL. The mixture was filtered and the filtrate A and the residue were recovered. (2) Mix the dregs from step (1) with red peony root, chuanxiong rhizome, prepared pinellia tuber, prepared licorice root, and asparagus root. Add water equal to 20 times the weight of the Chinese herbs and boil and decoct 4 times, each time for 1 hour. Filter, combine the filtrates, and recover filtrate B. (3) Combine filtrate A and filtrate B, concentrate, freeze dry to obtain the composition.

[0060] Example 3 A composition for improving diabetes mellitus with cerebrovascular disease, comprising the following raw materials by weight: 130 parts of kudzu root, 35 parts of angelica sinensis, 45 parts of red peony root, 22 parts of chuanxiong rhizome, 18 parts of prepared pinellia tuber, 11 parts of prepared licorice root, 22 parts of asparagus root, 45 parts of coptis root, and 23 parts of trichosanthes peel.

[0061] The method for preparing the composition is as follows: (1) Pueraria lobata, Angelica sinensis, Coptis chinensis and Trichosanthes kirilowii peel were extracted by reflux with 60% ethanol for 2 hours at an extraction temperature of 45℃ and a solid-liquid ratio of 1g:20mL. After filtration, filtrate A and residue were recovered. (2) Mix the dregs from step (1) with red peony root, chuanxiong rhizome, prepared pinellia tuber, prepared licorice root, and asparagus root. Add water equal to 30 times the weight of the Chinese herbs and boil twice, each time for 3 hours. Filter, combine the filtrates, and recover filtrate B. (3) Combine filtrate A and filtrate B, concentrate, freeze dry to obtain the composition.

[0062] Example 4 A composition for improving diabetes mellitus with cerebrovascular disease, comprising the following raw materials by weight: 100 parts of kudzu root, 20 parts of angelica sinensis, 30 parts of red peony root, 15 parts of chuanxiong rhizome, 10 parts of prepared pinellia tuber, 8 parts of prepared licorice root, 15 parts of asparagus root, 30 parts of coptis root, and 15 parts of trichosanthes peel.

[0063] The composition was prepared using the same method as in Example 1.

[0064] Example 5 A composition for improving diabetes mellitus with cerebrovascular disease, comprising the following raw materials by weight: 150 parts of kudzu root, 40 parts of angelica sinensis, 50 parts of red peony root, 25 parts of chuanxiong rhizome, 20 parts of prepared pinellia tuber, 13 parts of prepared licorice root, 26 parts of asparagus root, 50 parts of coptis root, and 27 parts of trichosanthes peel.

[0065] The composition was prepared using the same method as in Example 1.

[0066] Comparative Example 1 The traditional formula consists of the following ingredients by weight: 20 parts kudzu root, 5 parts angelica root, 5 parts peony root, 5 parts chuanxiong rhizome, 10 parts prepared pinellia tuber, 5 parts prepared licorice root, 10 parts fresh ginger, 5 parts scutellaria root, and 50 parts white bark of plum root.

[0067] Preparation method of the composition: Mix the raw material components, soak in water for 30 minutes, with the water level about 2-3 cm above the medicinal materials, bring to a boil over high heat, then simmer over low heat for 30-40 minutes (add water appropriately according to the water absorption of the medicinal materials to ensure that the pot does not burn during the decoction process); repeat the decoction once, combine the decoction liquids, concentrate and dry to obtain the composition of the traditional formula.

[0068] Comparative Example 2 Unlike Example 1, the peel of Trichosanthes kirilowii was replaced with an equal weight of Panax notoginseng.

[0069] Comparative Example 3 Unlike Example 1, Coptis chinensis was replaced with an equal weight of mulberry bark.

[0070] Comparative Example 4 Unlike Example 1, the weight ratio of each raw material component in the composition is different, but the rest is the same as in Example 1.

[0071] The raw materials of the composition by weight are: 60 parts of kudzu root, 40 parts of angelica, 40 parts of red peony root, 20 parts of chuanxiong rhizome, 30 parts of prepared pinellia tuber, 10 parts of prepared licorice root, 30 parts of asparagus root, 25 parts of coptis root, and 60 parts of trichosanthes peel.

[0072] Experiment 1: Experimental Detection of Improvement in Palpitation, Irritability, and Sleep Function Ben Tun Qi is a disease characterized by "Qi rushing upwards from the lower abdomen to the throat." Typical symptoms include: Qi rushing upwards from the lower abdomen, potentially reaching the chest and throat; during an attack, the patient feels fullness in the chest and ribs, and a feeling of suffocation in the throat; symptoms disappear after the attack subsides (the attack feels like death, then stops). Triggering factors: It is often triggered or aggravated by emotional fluctuations (such as anger, anxiety, depression), fatigue, or improper diet.

[0073] Some diabetic patients with cerebrovascular disease experience significant fluctuations in their Yin energy, leading to symptoms such as dizziness, palpitations, shortness of breath, irritability, anxiety, and depression. Therefore, it is necessary to improve these symptoms, enhance sleep quality, and alleviate anxiety.

[0074] 1. Experimental materials 1.1 Samples: Solid compositions obtained in each example and comparative example.

[0075] 1.2 Experimental Animals: Healthy SPF-grade male Kunming mice (18-22g) were randomly divided into one blank control group and nine experimental groups, with ten mice in each group. The sodium barbital sleep latency test was performed, and the average respiratory rate of the mice (within 5 minutes after falling asleep) was recorded.

[0076] 1.3 Dosage: The recommended dose for adults (based on a body weight of 60 kg) is 4.2 g daily, equivalent to 0.07 g / day / kg body weight. The experimental study set the dose at 10 times the recommended human dose, i.e., 0.70 g / kg body weight daily. The composition was prepared with sterilized water and administered orally once daily for 30 consecutive days via gavage, after which various indicators were measured.

[0077] The blank control group (0 g / kg BW) was replaced with distilled water (sterilized) instead of the test substance, and the daily gavage volume was the same as that of each composition group.

[0078] 2. Experimental Methods Sodium barbital sleep latency test After 30 days of continuous administration, 15 minutes after the last administration, each group of animals was intraperitoneally injected with sodium barbital at a dose of 290 mg / kg Bw. The disappearance of the righting reflex in mice was used as an indicator to observe whether the test substance could shorten the sleep latency of sodium barbital.

[0079] The average respiratory rate of the mice was recorded within 5 minutes after they fell asleep.

[0080] The results of each test indicator are shown in Table 1.

[0081] Table 1

[0082] In Table 1, within the same column of data, && This indicates that there was a significant difference between the blank control group and the example group. && P < 0.01; ## This indicates that the data from each comparative example group are significantly different from those from Example 1 group. ## P < 0.01.

[0083] Mice in the blank control group had a long sleep latency, were active, had short sleep duration, and high respiratory rate. As shown in Table 1, the composition in the embodiments of this invention significantly reduced sleep latency and average respiratory rate compared to traditional formulations (Comparative Example 1), conventional ingredients (Comparative Examples 2-3), and conventional proportions (Comparative Example 4). This indicates that the composition of this invention with specific components and proportions can significantly shorten sleep latency, improve dizziness, palpitations, and irritability; and significantly reduce average respiratory rate, improving symptoms such as chest and rib distension associated with "running piglet" syndrome.

[0084] Experiment 2: Detection of the effects of the composition on type 2 diabetes and cerebrovascular disease. 1. Laboratory animals Healthy adult male mice (C57BL / 6J, 12-16 weeks old, SPF grade, 24-30g) were used in this study. All animals were housed in a clean-grade animal facility under relatively constant environmental conditions (temperature 22℃±3℃, humidity 60%±5%; 12h light / 12h dark cycle). All mice were fed a standard diet and had free access to food and water. After acclimatization, the mice were randomly assigned to a control group and an experimental group for subsequent experiments.

[0085] 2. Modeling Method After being fed a high-fat diet for three weeks, mice in the experimental group were injected intraperitoneally with STZ (streptozotocin). STZ was dissolved in 0.1 mol / L citrate buffer to a concentration of 1% and administered intraperitoneally. The dosage for the experimental group was 50 mg / kg, and the mice were injected 12 hours after fasting (with water allowed), for 5 consecutive days.

[0086] Following injection, blood glucose levels in the experimental group mice were measured via the tail vein using a glucometer and blood glucose test strips. A blood glucose level >16.7 mmol / L was defined as hyperglycemia. Mice were continued to be fed a high-fat diet for 4 weeks, with blood glucose levels monitored. Mice with blood glucose levels >16.7 mmol / L were retained. Under hyperglycemic conditions, chronic cerebrovascular injury was naturally induced. An examination of eight mice revealed that the experimental group mice had blood glucose levels >16.7 mmol / L, elevated TNF-α and IL-6 levels, and cerebral blood flow decreased by more than 40% compared to the control group, indicating a successful establishment of a model of type 2 diabetes and cerebrovascular disease.

[0087] After the blank control group was fed with normal feed for three weeks, they were injected with an equal volume of 0.1 mol / L citrate buffer, and then fed normal feed for 4 weeks.

[0088] 3. Animal grouping Mice that successfully developed the model were randomly divided into 10 groups of 8 mice each: model control group, Example 1-Example 5 groups, and Comparative Example 1-Comparative Example 4 groups. Except for the model control group, each group was administered the combined formula of the respective group at 100 mg / kg / day and normal feed by gavage for 3 consecutive weeks. The model control group was administered physiological saline at 100 mg / kg / day and normal feed by gavage for 3 consecutive weeks.

[0089] Eight mice were used as a blank control group. No modeling was performed. They were given 100 mg / kg / day of physiological saline and normal feed by gavage for 3 consecutive weeks.

[0090] 4. Experimental Testing 4.1 New Object Recognition Ability Experiment In the new object recognition experiment, the preference for exploring new objects reflects that animals already have a relatively strong memory of old objects.

[0091] Before training begins, the operating box and objects must be cleaned to eliminate the influence of residual odors and excrement from the previous animal experiment.

[0092] Training period: Two identical objects, labeled A and B, were placed at opposite ends of a test chamber. Each group of mice was placed in the center of the chamber. The total number of times the mice explored each object (Exploratory Number), TA, and TB were recorded within 5 minutes. The counting criteria were: the mouse facing the object, with its nose touching or coming within 1 cm of the object. Any non-frontal contact with the object, or any movement over or onto the object to view it, was not counted as an exploration.

[0093] Testing Period: 24 hours after training, replace object B (one of the two identical objects) with a new object C, keeping all other conditions unchanged. Place mice sequentially into the testing box and record the total number of times each mouse explores the old and new objects within 5 minutes (Exploratory Number), denoted as TA' and TC respectively. The discrimination ratio = (TC...) The ratio of TA' / (TA'+TC))×100% was used as an indicator of cognitive function in mice; a higher recognition index indicates better memory ability in mice. The recognition index results for each group of mice are shown in Table 2.

[0094] Table 2

[0095] In Table 2, △△ This indicates a significant difference between the model control group and the blank control group. △△ P < 0.01 indicates that the model was successfully established; # and ## This indicates that the data from each comparative example group are significantly different from those from Example 1 group. # P < 0.05 ## P < 0.01.

[0096] As can be seen from the results in Table 2, the mice in the embodiment group of the present invention showed a significantly increased recognition index of the new object C compared with the control group, suggesting that the components and proportions described in the present invention can significantly increase the learning and memory abilities of mice compared with compositions that have replaced components or compositions with conventional formulations.

[0097] 4.2 Blood Glucose Testing: After the new object recognition ability experiment, fasting blood glucose was measured, and a suitable amount of blood was collected from the tail. Blood glucose levels were measured using a blood glucose meter. The blood glucose results are shown in Table 3.

[0098] 4.3 Detection of inflammatory factors: The levels of inflammatory factors TNF-α and IL-6 in serum were detected by ELISA (Enzyme-Linked Immunosorbent Assay Kit, RD Biotech, USA). The results are shown in Table 3.

[0099] 4.4 Cerebral blood flow detection in mice: Mice in each group were anesthetized and placed in a tray. The skin on the top of the mouse's head was cut open with surgical scissors, and any remaining hair at the cut site was cleaned with a cotton ball soaked in physiological saline. The mouse's head was then positioned directly under the camera of a laser Doppler flowmeter to observe blood flow. BFI stands for blood flow index, which refers to the mean cerebral blood flow index. The BFI results for each group of mice are shown in Table 3.

[0100] Table 3

[0101] In Table 3, within the same column of data, △ and △△ This indicates that the data in each group are significantly different from those in the model control group. △ P < 0.05 △△ P < 0.01; # and ## This indicates that the data from each comparative example group are significantly different from those from Example 1 group. # P < 0.05 ## P < 0.01.

[0102] As shown in Table 3, the interaction of the raw material components in the composition of the present invention results in a more significant reduction in blood glucose levels, TNF-α levels, and IL-6 levels compared to the traditional formulation (Comparative Example 1) and conventional components (Comparative Examples 2-3). Simultaneously, it increases cerebral blood flow, achieving a superior effect in restoring cerebral blood flow compared to the comparative examples with replaced components or the traditional formulation. The composition of the present invention shows significant improvement effects on diabetes and cerebrovascular diseases, reducing damage to cerebral blood vessels. Furthermore, the nine components in the composition of the present invention work in specific proportions, resulting in a superior effect on improving diabetes and cerebrovascular diseases compared to the conventionally formulated composition in Comparative Example 4, significantly regulating blood glucose and inflammation levels, and improving blood flow.

[0103] In summary, the composition of the present invention provides a superior effect in improving the symptoms of diabetes mellitus with cerebrovascular disease, significantly reducing blood glucose and inflammatory factor levels; improving the ability to recognize new objects, regulating blood glucose and blood lipid levels, significantly improving blood flow, increasing cerebral blood flow in mice; significantly reducing sleep latency and average respiratory rate, and improving symptoms such as chest and rib distension associated with "running piglet qi".

[0104] Finally, it should be noted that the above content is only used to illustrate the technical solution of the present invention, and is not intended to limit the scope of protection of the present invention. Simple modifications or equivalent substitutions made by those skilled in the art to the technical solution of the present invention do not depart from the essence and scope of the technical solution of the present invention.

Claims

1. A composition for improving diabetes mellitus accompanied by cerebrovascular disease, characterized in that, Raw materials include: The ingredients include kudzu root, angelica root, red peony root, chuanxiong rhizome, prepared pinellia tuber, prepared licorice root, asparagus root, coptis root, and trichosanthes peel.

2. The composition according to claim 1, characterized in that, The ingredients, by weight, include: 100-150 parts of kudzu root, 20-40 parts of angelica root, 30-50 parts of red peony root, 15-25 parts of chuanxiong rhizome, 10-20 parts of prepared pinellia tuber, 8-13 parts of prepared licorice root, 15-26 parts of asparagus root, 30-50 parts of coptis root, and 15-27 parts of trichosanthes peel.

3. The composition according to claim 2, characterized in that, The raw materials, by weight, include: 110-130 parts of kudzu root, 25-35 parts of angelica root, 35-45 parts of red peony root, 18-22 parts of chuanxiong rhizome, 13-18 parts of prepared pinellia tuber, 9-11 parts of prepared licorice root, 18-22 parts of asparagus root, 35-45 parts of coptis root, and 18-23 parts of trichosanthes peel.

4. The composition according to claim 3, characterized in that, The ingredients, by weight, include: 120 parts kudzu root, 30 parts angelica root, 40 parts red peony root, 20 parts chuanxiong rhizome, 15 parts prepared pinellia tuber, 10 parts prepared licorice root, 20 parts asparagus root, 40 parts coptis root, and 20 parts trichosanthes peel.

5. A method for preparing the composition according to any one of claims 1-4, characterized in that, Including the following steps: (1) Pueraria lobata, Angelica sinensis, Coptis chinensis and Trichosanthes kirilowii peel were extracted by ethanol reflux, filtered, and the filtrate A and the residue were recovered; (2) Mix the dregs from step (1) with red peony root, chuanxiong rhizome, prepared pinellia tuber, prepared licorice root, and asparagus root, decoct, filter, and recover filtrate B; (3) Combine filtrate A and filtrate B to obtain the composition.

6. The preparation method according to claim 5, characterized in that, In step (1), the reflux extraction is performed with an ethanol volume concentration of 35%-60%, reflux extraction at 45-65℃ for 2-4 hours, and an extraction solid-liquid ratio of 1g:20-30mL.

7. The preparation method according to claim 6, characterized in that, In step (1), the reflux extraction is performed with an ethanol volume concentration of 50%, reflux extraction at 55°C for 3 hours, and an extraction solid-liquid ratio of 1g:25mL.

8. The preparation method according to claim 5, characterized in that, In step (2), the decoction is specifically: boiled and decocted 2-4 times, each time for 1-3 hours; based on the total mass of all Chinese herbal raw materials, the solid-liquid ratio of the decoction is 1g:20-30mL.

9. The composition according to any one of claims 1-4 or the composition obtained by the preparation method according to any one of claims 5-8 is used in the preparation of a medicament for improving diabetes mellitus with cerebrovascular disease.

10. A drug for improving diabetes mellitus complicated with cerebrovascular disease, characterized in that, Includes the following components: the composition according to any one of claims 1-4 or the composition obtained by the preparation method according to any one of claims 5-8.

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