Traditional Chinese medicine composition for treating lower digestion type diabetes mellitus as well as preparation method and application of traditional Chinese medicine composition

Abstract

The invention discloses a traditional Chinese medicine composition for treating lower digestion type diabetes as well as a preparation method and application thereof, and relates to the technical field of traditional Chinese medicines. The traditional Chinese medicine composition comprises fortune eupatorium herb, rehmannia root, trichosanthes root, Chinese yam, astragalus root, figwort root, dwarf lilyturf tuber, tree peony bark, oriental waterplantain rhizome, tuckahoe, dogwood, safflower, turmeric, Chinese magnoliavine fruit, liquoric root, monkshood, cassia twig, dendrobium flower, glossy privet fruit, epimedium herb, corn stigma and hippophae rhamnoides leaf. Through reasonable compatibility of the traditional Chinese medicinal materials, the traditional Chinese medicinal composition with a remarkable treatment effect on the lower digestion type diabetes mellitus is obtained.

Description

Technical Field

[0001] This invention relates to the field of traditional Chinese medicine technology, specifically to a traditional Chinese medicine composition for treating diabetes mellitus of the lower limb type, its preparation method, and its application. Background Technology

[0002] Traditional Chinese medicine (TCM) defines diabetes as "Xiao Ke Bing" (wasting and thirsting disease). The *Neijing* (Inner Canon of Medicine) states that excessive consumption of rich and sweet foods, excessive alcohol and sexual activity, emotional imbalance, and weakness of the five internal organs are the main causes of Xiao Ke Bing. It broadly refers to a group of diseases caused by excessive intake of rich and sweet foods, excessive emotional fluctuations, unrestrained sexual activity, damage from pathogenic heat, or misuse of mineral drugs, leading to excessive heat in the stomach, fluid depletion, or lung heat causing dry skin, excessive heart fire, and damage to kidney yin. This results in dysfunction of qi transformation, causing uncontrolled downward flow of body fluids and essence, leading to a group of diseases with typical symptoms of polydipsia, polyphagia, and polyuria. Xiao Ke Bing symptoms are divided into three categories: Upper Xiao, Middle Xiao, and Lower Xiao (wasting the kidneys). Upper Xiao refers to polydipsia, middle Xiao to polyphagia, and lower Xiao (wasting the kidneys). Lower Xiao refers to polydipsia with persistent thirst, middle Xiao to polyphagia, and lower Xiao to polyuria with uncontrollable urination accompanied by a pasty discharge.

[0003] Lower wasting type diabetes is mainly caused by kidney yin deficiency. Traditional Chinese medicine often treats lower wasting type diabetes by nourishing kidney yin. In modern medicine, in addition to traditional Chinese medicine methods, the treatment of lower wasting type diabetes also includes the use of hypoglycemic drugs, such as insulin and metformin, to help regulate blood sugar levels.

[0004] The study, "A Preliminary Exploration of the Significance of the Three-Classification Method in the Clinical Application of Metformin," records that although the basic pathogenesis of the three types of wasting and thirsting syndromes is the same, the primary and secondary affected organs are the lungs, spleen, and kidneys, thus the treatment prescriptions also differ. The results showed that the TCM syndrome scores of all three groups of patients improved significantly compared to before treatment, and blood glucose levels decreased significantly. The overall effective rate of the upper and middle wasting and thirsting syndromes was significantly higher than that of the lower wasting and thirsting syndromes group, with the middle wasting and thirsting syndromes showing the most significant decrease in blood glucose. This indicates that metformin treatment is most effective for patients in the middle wasting and thirsting syndromes characterized by polyphagia, hunger, and weight loss.

[0005] The article "Treatment of 52 Cases of Type 2 Diabetes with Self-Formulated Xiaxiao Decoction" records that Xiaxiao Decoction is used, one dose per day, decocted in water and taken twice a day, morning and evening. The prescription is as follows: 20g each of Rehmannia glutinosa, Dioscorea opposita, Trichosanthes kirilowii, and Cornus officinalis; 15g each of Poria cocos, Eclipta prostrata, and Ligustrum lucidum; 10g each of Alisma plantago-aquatica, Paeonia suffruticosa, Ophiopogon japonicus, and Dendrobium nobile; and 5g each of Rosa laevigata and Citrus reticulata. For severe lower back and knee weakness, add 30g of Cistanche deserticola, 10g each of Achyranthes bidentata and Taxillus chinensis; for severe thirst, add 30g of Gypsum fibrosum, 10g of Anemarrhena asphodeloides, and 20g each of Dendrobium nobile and Ophiopogon japonicus; for severe dizziness and tinnitus, add 10g each of Gastrodia elata, Uncaria rhynchophylla, and raw oyster shell; for severe restlessness and insomnia, add 10g each of Schisandra chinensis and Ziziphus jujuba var. spinosa; for severe blurred vision, add 10g each of Lycium barbarum and Chrysanthemum morifolium; for severe bone steaming fever and night sweats, add 10g each of Lycium chinense root bark and turtle shell; for concurrent qi deficiency, add 30g of Astragalus membranaceus; for blood stasis, add 30g of Salvia miltiorrhiza; for severe edema, add 8g each of dried ginger and Atractylodes macrocephala, etc. Laboratory test results showed that all treatments were more effective than the control group, and the differences were statistically significant.

[0006] Chinese patent CN1196942A discloses a pharmaceutical composition for treating "lower-type" diabetes, comprising the following raw materials in weight percentages: 0.25%-0.35% glibenclamide, 6%-11% tortoise shell powder, 2.5%-3.5% centipede powder, 6%-11% chicken gizzard powder, 11%-16% cinnamon powder, and 58.15%-74.45% traditional Chinese medicine extract (containing Lycium chinense root bark, Lycium barbarum, Salvia miltiorrhiza, Leonurus japonicus, Morinda officinalis, Cornus officinalis, and corn silk). This pharmaceutical composition overcomes the shortcomings of current clinical use of chemically synthesized drugs, such as reliable short-term efficacy, unsatisfactory long-term efficacy, high toxicity and side effects, and sudden failure. It provides a new dosage form for clinical use, allowing for differentiated treatment based on the different symptoms of the three types of diabetes, combining traditional Chinese and Western medicine to treat both the symptoms and the root cause.

[0007] Lower-type diabetes differs from other types of diabetes, therefore the treatment methods also differ. Currently, there is still a lack of traditional Chinese medicine formulas for the treatment of lower-type diabetes. Summary of the Invention

[0008] In view of this, the purpose of this invention is to provide a traditional Chinese medicine composition for treating lower-type diabetes, its preparation method, and its application. Through the rational combination of traditional Chinese medicinal materials, this invention provides a traditional Chinese medicine composition with significant therapeutic effect, targeting the specific characteristics of lower-type diabetes caused by kidney yin deficiency.

[0009] To achieve the above-mentioned objectives, the technical solution of the present invention is as follows:

[0010] On one hand, the present invention provides a traditional Chinese medicine composition for treating diabetes mellitus, comprising: Eupatorium fortunei, Rehmannia glutinosa, Trichosanthes kirilowii, Dioscorea opposita, Astragalus membranaceus, Scrophularia ningpoensis, Ophiopogon japonicus, Paeonia suffruticosa, Alisma plantago-aquatica, Poria cocos, Cornus officinalis, Carthamus tinctorius, Curcuma longa, Schisandra chinensis, Glycyrrhiza uralensis, Aconitum carmichaelii, Cinnamomum cassia, Dendrobium nobile, Ligustrum lucidum, Epimedium brevicornu, corn silk, and Hippophae rhamnoides.

[0011] The solution of this invention is: Rehmannia glutinosa is sweet, cold, and moist. It nourishes yin and tonifies the kidneys, replenishes essence and marrow, and directly replenishes the kidney yin deficiency caused by lower wasting and thirsting. Ophiopogon japonicus nourishes yin and moistens the lungs, benefits the stomach and generates fluids. Together with Rehmannia glutinosa, they enhance the yin-nourishing power and relieve symptoms of yin deficiency and dryness such as thirst, excessive drinking, and frequent urination. The two are the principal herbs. Astragalus tonifies Qi and raises Yang, strengthens Wei Qi and consolidates the exterior, promotes diuresis and reduces swelling, and assists Rehmannia glutinosa in nourishing Yin. Scrophularia ningpoensis clears heat and cools blood, nourishes Yin and reduces fire, and works synergistically with Ophiopogon japonicus to enhance the Yin-nourishing and heat-clearing effects, relieving internal dryness and heat. Dioscorea opposita tonifies the spleen and stomach, generates fluids and benefits the lungs, tonifies the kidneys and astringes essence, and assists Astragalus tonifies Qi and consolidates kidney Qi. Eupatorium fortunei aromatically transforms dampness, invigorates the spleen and stimulates appetite. Trichosanthes kirilowii clears heat and generates fluids. All of the above are assistant herbs, which enhance the efficacy of the principal herbs and improve the state of Qi and Yin deficiency. Safflower, turmeric, and peony bark invigorate blood circulation, relieve pain, and improve blood flow. Alisma, Poria, and corn silk promote diuresis, eliminate dampness, clear heat, reduce turbidity, prevent water retention, and reduce metabolic burden. Aconitum, cinnamon twig, and epimedium warm and tonify the spleen and kidney yang. Schisandra chinensis astringes and consolidates. Cornus officinalis tonifies the liver and kidney. All of the above are adjuvant herbs to harmonize the properties of the principal and assistant herbs. Licorice harmonizes the effects of the other herbs, tonifies the spleen and replenishes qi, clears heat and detoxifies. Dendrobium flowers, privet fruit, and sea buckthorn leaves assist in nourishing yin, tonifying the liver and kidneys, and enhancing the targeted nature of the drugs. All of these serve as guiding herbs, coordinating the properties of the entire formula to ensure precise and effective treatment.

[0012] Preferably, the traditional Chinese medicine composition for treating diabetes mellitus includes, by weight, the following ingredients: 10-50 parts of Eupatorium fortunei, 10-50 parts of Rehmannia glutinosa, 10-50 parts of Trichosanthes kirilowii, 10-50 parts of Dioscorea opposita, 10-50 parts of Astragalus membranaceus, 10-50 parts of Scrophularia ningpoensis, 5-50 parts of Ophiopogon japonicus, 5-40 parts of Paeonia suffruticosa, 5-40 parts of Alisma plantago-aquatica, 5-40 parts of Poria cocos, 5-40 parts of Cornus officinalis, 1-20 parts of Carthamus tinctorius, 1-20 parts of Curcuma longa, 1-20 parts of Schisandra chinensis, 1-20 parts of Glycyrrhiza uralensis, 1-20 parts of Aconitum carmichaelii, 1-20 parts of Cinnamomum cassia, 10-50 parts of Dendrobium nobile, 0-30 parts of Ligustrum lucidum, 0-30 parts of Epimedium brevicornu, 10-50 parts of Zea mays silk, and 5-30 parts of Hippophae rhamnoides leaf.

[0013] More preferably, the traditional Chinese medicine composition for treating diabetes mellitus includes, by weight: 20-40 parts of Eupatorium fortunei, 20-40 parts of Rehmannia glutinosa, 20-40 parts of Trichosanthes kirilowii, 20-40 parts of Dioscorea opposita, 20-40 parts of Astragalus membranaceus, 20-40 parts of Scrophularia ningpoensis, 20-30 parts of Ophiopogon japonicus, 10-20 parts of Paeonia suffruticosa, 10-20 parts of Alisma plantago-aquatica, 10-20 parts of Poria cocos, 10-20 parts of Cornus officinalis, 5-15 parts of Carthamus tinctorius, 5-15 parts of Curcuma longa, 5-15 parts of Schisandra chinensis, 5-12 parts of Glycyrrhiza uralensis, 5-15 parts of Aconitum carmichaelii, 5-15 parts of Cinnamomum cassia, 20-30 parts of Dendrobium nobile, 5-15 parts of Ligustrum lucidum, 5-15 parts of Epimedium brevicornu, 25-35 parts of Zea mays silk, and 10-20 parts of Hippophae rhamnoides.

[0014] Most preferably, the traditional Chinese medicine composition for treating diabetes mellitus includes, by weight: 30 parts of Eupatorium fortunei, 30 parts of Rehmannia glutinosa, 30 parts of Trichosanthes kirilowii, 30 parts of Dioscorea opposita, 30 parts of Astragalus membranaceus, 30 parts of Scrophularia ningpoensis, 25 parts of Ophiopogon japonicus, 15 parts of Paeonia suffruticosa, 15 parts of Alisma plantago-aquatica, 15 parts of Poria cocos, 15 parts of Cornus officinalis, 10 parts of Carthamus tinctorius, 10 parts of Curcuma longa, 10 parts of Schisandra chinensis, 8 parts of Glycyrrhiza uralensis, 10 parts of Aconitum carmichaelii, 10 parts of Cinnamomum cassia, 25 parts of Dendrobium nobile, 10 parts of Ligustrum lucidum, 10 parts of Epimedium brevicornu, 30 parts of Zea mays silk, and 15 parts of Hippophae rhamnoides leaf.

[0015] Preferably, the Rehmannia glutinosa is raw Rehmannia glutinosa or processed Rehmannia glutinosa.

[0016] Preferably, the Astragalus membranaceus is processed Astragalus membranaceus.

[0017] Secondly, the present invention provides a method for preparing the above-mentioned traditional Chinese medicine composition, comprising the following steps: (1) The formula amounts of Eupatorium fortunei, Rehmannia glutinosa, Trichosanthes kirilowii, Dioscorea opposita, Astragalus membranaceus, Scrophularia ningpoensis, Ophiopogon japonicus, Paeonia suffruticosa, Alisma plantago-aquatica, Poria cocos, Cornus officinalis, Carthamus tinctorius, Curcuma longa, Schisandra chinensis, Glycyrrhiza uralensis, Aconitum carmichaelii, Cinnamomum cassia and Corn silk are pulverized, cell wall broken, and extracted with water 2-5 times. The filtrates are combined, centrifuged, and concentrated to obtain extract 1. (2) Crush the Dendrobium flowers, Ligustrum lucidum, Epimedium and Hippophae rhamnoides leaves in the prescribed amount, break the cell wall, extract with ethanol solution 1-3 times, combine the filtrates, centrifuge, concentrate with ultrafiltration membrane to obtain extract 2; (3) Mix extract 1 and extract 2 and dry them to obtain the final product.

[0018] Preferably, in step (1), the water extraction specifically involves: extracting 2-3 times, adding 5-20 times the weight of water to be extracted each time, extracting at 80°C or above for 30-120 minutes, and then combining the extracts.

[0019] Preferably, in step (2), the extraction with ethanol solution specifically involves: extracting 2-3 times, each time adding 5-15 times the weight of the substance to be extracted with ethanol solution, wherein the ethanol solution is an aqueous solution with a volume fraction of 40%-70%, and extracting at 30-50°C or above for 30-60 minutes, and then combining the extracts.

[0020] Preferably, in step (2), the ultrafiltration membrane is a polyethersulfone membrane or a polyvinylidene fluoride membrane with a molecular weight cutoff of 20-50 kDa.

[0021] Preferably, in step (3), the drying can be selected from commonly used drying methods in the art, such as freeze drying, rotary drying, vacuum drying, baking, spray drying, etc., so that the product moisture content is controlled below 1%.

[0022] As a specific example of the present invention, the preparation method of the traditional Chinese medicine composition includes the following steps: (1) The following ingredients in the formula amount are crushed, mixed, cell wall broken, extracted with water 3 times, each time with 15 times the weight of the extract to be extracted, and extracted at 85℃ for 60 min. The extracts are combined, filtered, centrifuged, concentrated, and extract 1. (2) The prescribed amounts of Dendrobium flowers, Ligustrum lucidum, Epimedium and Hippophae rhamnoides leaves were ultra-finely pulverized, mixed, and extracted twice. Each time, 10 times the weight of the extract was added to an ethanol solution, which was a 50% ethanol aqueous solution. The extraction was carried out at 35°C for 40 min. The extracts were combined, filtered, centrifuged, and concentrated using a polyethersulfone membrane (40 kDa) to obtain extract 2. (3) Spray dry extract 1 and extract 2 to obtain the final product.

[0023] Thirdly, the present invention provides the use of the above-mentioned traditional Chinese medicine composition in the preparation of medicaments for treating and / or preventing diabetes.

[0024] Preferably, the diabetes mellitus is lower biliary diabetes.

[0025] Furthermore, the symptoms of lower-grade diabetes mellitus include frequent urination, dark green urine, excessive thirst, irritability, a red tongue with little coating, and a thready and rapid pulse. The treatment should focus on nourishing yin and strengthening the kidneys, replenishing qi and promoting body fluid production.

[0026] Fourthly, the present invention provides a medicine whose active ingredients include the above-mentioned traditional Chinese medicine composition.

[0027] The drug can be prepared into dosage forms such as pills, capsules, granules, oral liquids, powders, tablets, lozenges, and sugar lozenges. For different dosage forms, a suitable drug carrier in this field can be selected.

[0028] The drug carrier used can be solid, liquid, or gaseous. 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. Examples of gaseous carriers include carbon dioxide and nitrogen.

[0029] 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.

[0030] Tablets containing the traditional Chinese medicine composition of the present invention can be prepared by compression or molding, and one or more excipients or adjuvants may be used. 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 powdery mixture moistened with an inert liquid diluent, each tablet preferably containing about 0.05 mg to about 5 g of active ingredient, and each sachet or capsule preferably containing 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 drug, 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.

[0031] The pharmaceutical compositions of this invention suitable for parenteral administration can be prepared as aqueous solutions or suspensions of the active compound and may include suitable surfactants, such as hydroxypropyl cellulose. Dispersions can also be prepared in mixtures of glycerol, liquid polyethylene glycol, and their oils. Furthermore, preservatives may be added to prevent harmful microbial growth.

[0032] The medicaments of the present invention can be in forms suitable for topical use, such as aerosols, creams, ointments, lotions, powders, or the like. Furthermore, the compositions can be in suitable forms for transdermal drug delivery devices. These formulations can be prepared using the traditional Chinese medicine compositions of the present invention through conventional processing methods. For example, a cream or ointment with a desired consistency can be prepared by mixing a hydrophilic material and water, and about 5 wt% to about 10 wt% of the compound.

[0033] The medicament of the present invention can be in a form suitable for rectal administration, wherein the carrier is solid. It is preferable to formulate the mixture into a single-dose suppository. Suitable carriers include cocoa butter and other materials commonly used in the art. Suppositories can be made by first forming a mixture containing a softened or melted carrier, followed by cooling and shaping in a mold.

[0034] 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, colorants, and flavoring agents, and the components containing the traditional Chinese medicine composition of this invention can also be prepared in powder or concentrated form.

[0035] The beneficial effects of this invention are as follows: This invention achieves significant hypoglycemic and kidney-tonifying effects by selecting and rationally proportioning a combination of herbs such as Eupatorium fortunei, Rehmannia glutinosa, Trichosanthes kirilowii, Dioscorea opposita, Astragalus membranaceus, Scrophularia ningpoensis, Ophiopogon japonicus, Paeonia suffruticosa, Alisma plantago-aquatica, Poria cocos, Cornus officinalis, Carthamus tinctorius, Curcuma longa, Schisandra chinensis, Glycyrrhiza uralensis, Aconitum carmichaelii, Cinnamomum cassia, Dendrobium nobile, Ligustrum lucidum, Epimedium brevicornu, Zea mays silk, and Hippophae rhamnoides leaves, and employing specific extraction processes. Furthermore, the combination is tailored to the specific characteristics of lower wasting-type diabetes, resulting in better therapeutic effects and making it more suitable for the treatment of patients with lower wasting-type diabetes. Detailed Implementation

[0036] To make the technical means, creative features, and achieved objectives and effects of this invention easier to understand, the invention is further illustrated below with specific embodiments. However, the following embodiments are merely preferred embodiments of this invention and not all embodiments. Other embodiments obtained by those skilled in the art based on the embodiments described herein without creative effort are all within the protection scope of this invention. Unless otherwise specified, the operating methods and equipment used in the following embodiments are conventional operating methods, and the materials and equipment used in each embodiment are the same.

[0037] In the following examples, Rehmannia glutinosa is prepared Rehmannia glutinosa and Astragalus membranaceus is processed Astragalus membranaceus.

[0038] Example 1 Formula: 50 parts of Eupatorium fortunei, 50 parts of Rehmannia glutinosa, 50 parts of Trichosanthes kirilowii, 50 parts of Dioscorea opposita, 10 parts of Astragalus membranaceus, 10 parts of Scrophularia ningpoensis, 5 parts of Ophiopogon japonicus, 5 parts of Paeonia suffruticosa, 5 parts of Alisma plantago-aquatica, 40 parts of Poria cocos, 40 parts of Cornus officinalis, 20 parts of Carthamus tinctorius, 20 parts of Curcuma longa, 1 part of Schisandra chinensis, 1 part of Glycyrrhiza uralensis, 1 part of Aconitum carmichaelii, 1 part of Cinnamomum cassia, 50 parts of Dendrobium nobile, 50 parts of Zea mays silk, and 30 parts of Hippophae rhamnoides leaves.

[0039] Example 2 Formula: 10 parts of Eupatorium fortunei, 10 parts of Rehmannia glutinosa, 10 parts of Trichosanthes kirilowii, 10 parts of Dioscorea opposita, 50 parts of Astragalus membranaceus, 50 parts of Scrophularia ningpoensis, 50 parts of Ophiopogon japonicus, 40 parts of Paeonia suffruticosa, 40 parts of Alisma plantago-aquatica, 5 parts of Poria cocos, 5 parts of Cornus officinalis, 1 part of Carthamus tinctorius, 1 part of Curcuma longa, 20 parts of Schisandra chinensis, 20 parts of Glycyrrhiza uralensis, 20 parts of Aconitum carmichaelii, 1 part of Cinnamomum cassia, 10 parts of Dendrobium nobile, 30 parts of Ligustrum lucidum, 30 parts of Epimedium brevicornu, 10 parts of Zea mays silk, and 5 parts of Hippophae rhamnoides leaves.

[0040] Example 3 Formula: 20 parts of Eupatorium fortunei, 20 parts of Rehmannia glutinosa, 40 parts of Trichosanthes kirilowii, 20 parts of Dioscorea opposita, 40 parts of Astragalus membranaceus, 40 parts of Scrophularia ningpoensis, 20 parts of Ophiopogon japonicus, 20 parts of Paeonia suffruticosa, 20 parts of Alisma plantago-aquatica, 10 parts of Poria cocos, 10 parts of Cornus officinalis, 5 parts of Carthamus tinctorius, 15 parts of Curcuma longa, 15 parts of Schisandra chinensis, 12 parts of Glycyrrhiza uralensis, 5 parts of Aconitum carmichaelii, 5 parts of Cinnamomum cassia, 30 parts of Dendrobium nobile, 5 parts of Ligustrum lucidum, 5 parts of Epimedium brevicornu, 25 parts of corn silk, and 10 parts of Hippophae rhamnoides leaves.

[0041] Example 4 Formula: 40 parts of Eupatorium fortunei, 40 parts of Rehmannia glutinosa, 20 parts of Trichosanthes kirilowii, 40 parts of Dioscorea opposita, 20 parts of Astragalus membranaceus, 20 parts of Scrophularia ningpoensis, 30 parts of Ophiopogon japonicus, 10 parts of Paeonia suffruticosa, 10 parts of Alisma plantago-aquatica, 20 parts of Poria cocos, 20 parts of Cornus officinalis, 15 parts of Carthamus tinctorius, 5 parts of Curcuma longa, 5 parts of Schisandra chinensis, 5 parts of Glycyrrhiza uralensis, 5 parts of Aconitum carmichaelii, 15 parts of Cinnamomum cassia, 30 parts of Dendrobium nobile, 5 parts of Ligustrum lucidum, 5 parts of Epimedium brevicornu, 25 parts of corn silk, and 20 parts of Hippophae rhamnoides leaves.

[0042] Example 5 Formula: 30 parts of Eupatorium fortunei, 30 parts of Rehmannia glutinosa, 30 parts of Trichosanthes kirilowii, 30 parts of Dioscorea opposita, 30 parts of Astragalus membranaceus, 30 parts of Scrophularia ningpoensis, 25 parts of Ophiopogon japonicus, 15 parts of Paeonia suffruticosa, 15 parts of Alisma plantago-aquatica, 15 parts of Poria cocos, 15 parts of Cornus officinalis, 10 parts of Carthamus tinctorius, 10 parts of Curcuma longa, 10 parts of Schisandra chinensis, 8 parts of Glycyrrhiza uralensis, 10 parts of Aconitum carmichaelii, 10 parts of Cinnamomum cassia, 25 parts of Dendrobium nobile, 10 parts of Ligustrum lucidum, 10 parts of Epimedium brevicornu, 30 parts of Zea mays silk, and 15 parts of Hippophae rhamnoides leaves.

[0043] Comparative Example 1 Formula: 20 parts Rehmannia glutinosa, 20 parts Dioscorea opposita, 20 parts Trichosanthes kirilowii, 20 parts Cornus officinalis, 15 parts Poria cocos, 15 parts Eclipta prostrata, 15 parts Ligustrum lucidum, 10 parts Alisma plantago-aquatica, 10 parts Paeonia suffruticosa, 10 parts Ophiopogon japonicus, 10 parts Dendrobium nobile, 5 parts Rosa laevigata, 5 parts Citrus reticulata, 30 parts Gypsum fibrosum, 10 parts Anemarrhena asphodeloides, 20 parts Dendrobium nobile, 20 parts Ophiopogon japonicus, 10 parts Gastrodia elata, 10 parts Uncaria rhynchophylla, 10 parts Ostrea gigas, 10 parts Schisandra chinensis, 10 parts Ziziphus jujuba var. spinosa, 10 parts Lycium barbarum, 10 parts Carapax Trionycis, 30 parts Astragalus membranaceus, 30 parts Salvia miltiorrhiza, 8 parts Zingiber officinale, 8 parts Atractylodes macrocephala.

[0044] Comparative Example 2 Formula: 30 parts of Eupatorium fortunei, 30 parts of Rehmannia glutinosa, 30 parts of Trichosanthes kirilowii, 30 parts of Dioscorea opposita, 30 parts of Astragalus membranaceus, 30 parts of Scrophularia ningpoensis, 25 parts of Ophiopogon japonicus, 15 parts of Paeonia suffruticosa, 15 parts of Alisma plantago-aquatica, 15 parts of Poria cocos, 15 parts of Cornus officinalis, 10 parts of Carthamus tinctorius, 10 parts of Curcuma longa, 10 parts of Schisandra chinensis, 8 parts of Glycyrrhiza uralensis, 10 parts of Aconitum carmichaelii, 10 parts of Cinnamomum cassia, 20 parts of Ligustrum lucidum, 10 parts of Epimedium brevicornu, 30 parts of corn silk, and 30 parts of Hippophae rhamnoides leaves.

[0045] Comparative Example 3 Formula: 30 parts of Eupatorium fortunei, 30 parts of Rehmannia glutinosa, 30 parts of Atractylodes macrocephala, 30 parts of Trichosanthes kirilowii, 30 parts of Astragalus membranaceus, 30 parts of Scrophularia ningpoensis, 25 parts of Ophiopogon japonicus, 15 parts of Salvia miltiorrhiza, 15 parts of Alisma plantago-aquatica, 15 parts of Poria cocos, 15 parts of Cornus officinalis, 10 parts of Carthamus tinctorius, 10 parts of Curcuma longa, 10 parts of Schisandra chinensis, 8 parts of Glycyrrhiza uralensis, 10 parts of Aconitum carmichaelii, 10 parts of Cinnamomum cassia, 25 parts of Dendrobium nobile, 10 parts of Ligustrum lucidum, 10 parts of Epimedium brevicornu, 30 parts of Zea mays silk, and 15 parts of Hippophae rhamnoides leaves.

[0046] Comparative Example 4 Formula: 5 parts of Eupatorium fortunei, 50 parts of Rehmannia glutinosa, 5 parts of Dioscorea opposita, 50 parts of Trichosanthes kirilowii, 60 parts of Astragalus membranaceus, 60 parts of Scrophularia ningpoensis, 25 parts of Ophiopogon japonicus, 15 parts of Paeonia suffruticosa, 15 parts of Alisma plantago-aquatica, 15 parts of Poria cocos, 50 parts of Cornus officinalis, 30 parts of Carthamus tinctorius, 30 parts of Curcuma longa, 30 parts of Schisandra chinensis, 30 parts of Glycyrrhiza uralensis, 10 parts of Aconitum carmichaelii, 10 parts of Cinnamomum cassia, 5 parts of Dendrobium nobile, 10 parts of Ligustrum lucidum, 40 parts of Epimedium brevicornu, 5 parts of Zea mays silk, and 5 parts of Hippophae rhamnoides leaves.

[0047] The preparation methods of Examples 1-5 and Comparative Examples 1-4 are as follows: (1) The following ingredients in the formula amount are crushed, mixed, and extracted with water 3 times. Each time, 15 times the weight of the extract is added to water. The extract is extracted at 85℃ for 60 min. The extracts are combined, filtered, centrifuged at 10000 r / min for 15 min, and concentrated under reduced pressure to obtain extract 1 (thick paste, density 1.20 (60℃)). (2) The amount of Dendrobium flowers, Ligustrum lucidum, Epimedium and Hippophae rhamnoides leaves in the formula are crushed, mixed, and subjected to cell wall breaking treatment. The mixture is extracted twice with ethanol. Each time, 10 times the weight of the extract is added to the ethanol solution, which is a 50% ethanol aqueous solution. The mixture is extracted at 35°C for 40 min. The extracts are combined, filtered, centrifuged at 10000 r / min for 15 min, and then concentrated with a polyethersulfone membrane (40 kDa, 2.5 bar) to obtain extract 2. (3) Mix extract 1 and extract 2, spray dry, and pass through a 150-mesh sieve to obtain a powdered Chinese medicine composition.

[0048] Comparative Example 5 The formula is the same as in Example 5, and the preparation method is as follows: Weigh all the medicinal ingredients according to the formula, crush them, mix them, and extract them three times with water. Each time, add 10 times the weight of the extract and extract at 85°C or above for 60 minutes. Combine the extracts and centrifuge them at 10,000 r / min for 15 minutes. Then concentrate them with a polyethersulfone membrane (40 kDa, 2.5 bar), spray dry them, and pass them through a 150-mesh sieve to obtain a powdered traditional Chinese medicine composition.

[0049] Result detection 1. Improvement effect on kidney yin deficiency Experimental animals and model establishment: Male SD rats, weighing 180-200g, were acclimatized for one week and randomly divided into blank group, model group, positive drug group, Examples 1-5 groups, and Comparative Examples 1-5 groups, with 10 rats in each group. The housing environment was kept well-ventilated, with a temperature of 22±1℃ and humidity maintained at 55%-65%, with a 12-hour light-dark cycle. During the experiment, rats had free access to water and food.

[0050] Except for the control group, all other groups were administered hydrocortisone injection (25 mg / kg) by gavage at 10:00 AM on days 1-12. The positive control group, Examples 1-5, and Comparative Examples 1-5 were simultaneously treated with the drug at 6:00 PM on days 1-12.

[0051] Administration method:

[0052] Administration route: Gavage administration. The blank group and the model group were given the same volume of distilled water by gavage. The gavage volume was 10 mL / kg, once a day.

[0053] Compared with the control group, the rats in the kidney yin deficiency model group showed yellowish fur, significantly increased water intake, significantly decreased food intake, and slower weight gain, indicating that the rat model of kidney yin deficiency was successfully established. After 12 days, the levels of testosterone (T), thyroxine (T4), and cortisol (COR) in each group of rats were detected by enzyme-linked immunosorbent assay (ELISA). The results are as follows:

[0054] Note: Comparison between the model group and the blank group. ### P < 0.001; compared with the model group, the experimental group, & P < 0.05 && P < 0.01, &&& P < 0.001; other experimental groups compared with Example 5, P < 0.05 P < 0.01.

[0055] The results show that the traditional Chinese medicine compositions prepared in Examples 1-5 of this invention can significantly improve the symptoms of kidney yin deficiency. Among them, Example 5 showed the best improvement effect, which was basically close to the positive control drug level. The formulation of Comparative Example 1 had a poor effect on improving kidney yin deficiency, and Comparative Examples 2 and 3 were other formulations before the adjustment of the formulation of this invention, and their effects were significantly lower than those of Example 5. Comparative Example 4 shows that under the reasonable weight ratio of the prescription of this invention, the effect of improving kidney yin deficiency can be significantly improved. The results of Comparative Example 5 show that this invention significantly improves the activity of the extract by selecting different extraction methods according to the characteristics of the medicinal materials.

[0056] 2. Improves metabolic effects Experimental animals and model establishment: Male SD rats, weighing 180-200g, were acclimatized for one week and randomly divided into a blank group, a model group, a positive drug group, Example 1-5 groups, and Comparative Example 1-5 groups, with 10 rats in each group. The housing environment was kept well-ventilated, with a temperature of 22±1℃ and humidity maintained at 55%-65%, and a 12-hour light-dark cycle. Free access to water and food was provided throughout the experiment.

[0057] The control group was fed a basal diet, while the other groups were fed a high-fat, high-sugar diet (10% lard, 20% sucrose, 2.5% cholesterol, 1% bile salts, 5% egg yolk powder, and 61.5% normal feed). After 4 weeks of continuous feeding, the rats were fasted but allowed free water for 12 hours. Except for the control group, all other groups were injected intraperitoneally with 1% STZ (streptozotocin) solution at a dose of 35 mg / kg; the control group was injected with an equal dose of 0.1 mol / L citrate-sodium citrate buffer solution (pH 4.2). 72 hours after injection, blood glucose was measured by tail vein sampling. A random blood glucose level higher than 14.2 mmol / L was considered a successful induction of diabetes.

[0058] Administration method:

[0059] Administration route: Gavage administration. The blank group and the model group were given the same volume of distilled water by gavage. The gavage volume was 10 mL / kg, once a day, for 4 consecutive weeks.

[0060] After fasting for 12 hours following the last administration, blood was collected from the tail vein and the blood glucose level was measured using a glucometer. Then, rats were anesthetized with chloral hydrate, and blood was collected from the abdominal aorta. After centrifugation, serum total cholesterol (TC), triglycerides (TG), high-density lipoprotein (HDL-C), and low-density lipoprotein (LDL-C) were measured using a kit. One-way ANOVA was performed between groups using SPSS 13.0 software.

[0061] The blood glucose test results are as follows:

[0062] Note: Comparison between the model group and the blank group. ### P < 0.001; compared with the model group, the experimental group, && P < 0.01, &&& P < 0.001; other experimental groups compared with Example 5, P < 0.05 P < 0.01.

[0063] The results showed that the traditional Chinese medicine compositions prepared in Examples 1-5 of this invention could significantly reduce blood glucose levels in rats. Examples 3 and 5 showed the best improvement effects, essentially approaching the levels of the positive control drug. Comparative Examples 2 and 3 were other formulations before the adjustment of the present invention. The weight ratio of the prescription in Comparative Example 4 differed from that in Example 5, and its results showed a significant decrease compared to Example 5. The extraction method of Comparative Example 5 differed from that in Example 5, and its results showed a significant decrease compared to Example 5.

[0064] The results of the determination of TC, TG, HDL-C, and LDL-C are as follows:

[0065] Note: Comparison between the model group and the blank group. # P < 0.05 ## P < 0.01, ### P < 0.001; compared with the model group, the experimental group, & P < 0.05 && P < 0.01, &&& P < 0.001; other experimental groups compared with Example 5, P < 0.05 P < 0.01.

[0066] Lipid metabolism abnormalities mainly refer to excessively high serum cholesterol or triglyceride levels. The results show that the traditional Chinese medicine compositions prepared in Examples 1-5 of this invention can significantly improve lipid metabolism levels and lower serum cholesterol in diabetic patients. Examples 3, 4, and 5 showed the best improvement effects, essentially approaching the levels of the positive control drug. Comparative Example 1 represents other existing formulations, and Comparative Examples 2 and 3 represent other formulations before adjustments to the formulation of this invention. The weight ratio of the formulation in Comparative Example 4 differs from that in Example 5, yet its results show a significant decrease compared to Example 5. Furthermore, different dosage groups of the composition prepared in Example 5 were verified, demonstrating a dose-dependent effect in lowering blood sugar and regulating lipid metabolism.

[0067] The results are as follows:

[0068] The above description is only a preferred embodiment of the present invention and is not intended to limit the present invention. Any modifications, equivalent substitutions, improvements, etc., made within the spirit and principles of the present invention should be included within the protection scope of the present invention.

Claims

1. A traditional Chinese medicine composition for treating diabetes mellitus type 2, characterized in that, include: Eupatorium fortunei, Rehmannia glutinosa, Trichosanthes kirilowii, Dioscorea opposita, Astragalus membranaceus, Scrophularia ningpoensis, Ophiopogon japonicus, Paeonia suffruticosa, Alisma plantago-aquatica, Poria cocos, Cornus officinalis, Carthamus tinctorius, Curcuma longa, Schisandra chinensis, Glycyrrhiza uralensis, Aconitum carmichaelii, Cinnamomum cassia, Dendrobium nobile, Ligustrum lucidum, Epimedium brevicornu, corn silk, and Hippophae rhamnoides leaves.

2. The traditional Chinese medicine composition according to claim 1, characterized in that, The traditional Chinese medicine composition for treating diabetes mellitus includes, by weight, the following ingredients: 10-50 parts of Eupatorium fortunei, 10-50 parts of Rehmannia glutinosa, 10-50 parts of Trichosanthes kirilowii, 10-50 parts of Dioscorea opposita, 10-50 parts of Astragalus membranaceus, 10-50 parts of Scrophularia ningpoensis, 5-50 parts of Ophiopogon japonicus, 5-40 parts of Paeonia suffruticosa, 5-40 parts of Alisma plantago-aquatica, 5-40 parts of Poria cocos, 5-40 parts of Cornus officinalis, 1-20 parts of Carthamus tinctorius, 1-20 parts of Curcuma longa, 1-20 parts of Schisandra chinensis, 1-20 parts of Glycyrrhiza uralensis, 1-20 parts of Aconitum carmichaelii, 1-20 parts of Cinnamomum cassia, 10-50 parts of Dendrobium nobile, 0-30 parts of Ligustrum lucidum, 0-30 parts of Epimedium brevicornu, 10-50 parts of Zea mays silk, and 5-30 parts of Hippophae rhamnoides leaf.

3. The traditional Chinese medicine composition according to claim 2, characterized in that, The traditional Chinese medicine composition for treating diabetes mellitus includes, by weight, the following ingredients: 20-40 parts of Eupatorium fortunei, 20-40 parts of Rehmannia glutinosa, 20-40 parts of Trichosanthes kirilowii, 20-40 parts of Dioscorea opposita, 20-40 parts of Astragalus membranaceus, 20-40 parts of Scrophularia ningpoensis, 20-30 parts of Ophiopogon japonicus, 10-20 parts of Paeonia suffruticosa, 10-20 parts of Alisma plantago-aquatica, 10-20 parts of Poria cocos, 10-20 parts of Cornus officinalis, 5-15 parts of Carthamus tinctorius, 5-15 parts of Curcuma longa, 5-15 parts of Schisandra chinensis, 5-12 parts of Glycyrrhiza uralensis, 5-15 parts of Aconitum carmichaelii, 5-15 parts of Cinnamomum cassia, 20-30 parts of Dendrobium nobile, 5-15 parts of Ligustrum lucidum, 5-15 parts of Epimedium brevicornu, 25-35 parts of Zea mays silk, and 10-20 parts of Hippophae rhamnoides leaf.

4. The traditional Chinese medicine composition according to claim 3, characterized in that, The traditional Chinese medicine composition for treating diabetes mellitus includes, by weight, the following ingredients: 30 parts of Eupatorium fortunei, 30 parts of Rehmannia glutinosa, 30 parts of Trichosanthes kirilowii, 30 parts of Dioscorea opposita, 30 parts of Astragalus membranaceus, 30 parts of Scrophularia ningpoensis, 25 parts of Ophiopogon japonicus, 15 parts of Paeonia suffruticosa, 15 parts of Alisma plantago-aquatica, 15 parts of Poria cocos, 15 parts of Cornus officinalis, 10 parts of Carthamus tinctorius, 10 parts of Curcuma longa, 10 parts of Schisandra chinensis, 8 parts of Glycyrrhiza uralensis, 10 parts of Aconitum carmichaelii, 10 parts of Cinnamomum cassia, 25 parts of Dendrobium nobile, 10 parts of Ligustrum lucidum, 10 parts of Epimedium brevicornu, 30 parts of Zea mays silk, and 15 parts of Hippophae rhamnoides leaf.

5. The traditional Chinese medicine composition according to any one of claims 1-4, characterized in that, The Rehmannia glutinosa is either raw or processed, and the Astragalus membranaceus is processed.

6. A method for preparing the traditional Chinese medicine composition according to any one of claims 1-5, characterized in that, Includes the following steps: (1) The formula amounts of Eupatorium fortunei, Rehmannia glutinosa, Trichosanthes kirilowii, Dioscorea opposita, Astragalus membranaceus, Scrophularia ningpoensis, Ophiopogon japonicus, Paeonia suffruticosa, Alisma plantago-aquatica, Poria cocos, Cornus officinalis, Carthamus tinctorius, Curcuma longa, Schisandra chinensis, Glycyrrhiza uralensis, Aconitum carmichaelii, Cinnamomum cassia and Corn silk are pulverized, cell wall broken, and extracted with water 2-5 times. The filtrates are combined, centrifuged, and concentrated to obtain extract 1. (2) Crush the Dendrobium flowers, Ligustrum lucidum, Epimedium and Hippophae rhamnoides leaves in the prescribed amount, break the cell wall, extract with ethanol solution 1-3 times, combine the filtrates, centrifuge, concentrate with ultrafiltration membrane to obtain extract 2; (3) Mix extract 1 and extract 2 and dry them to obtain the final product.

7. The preparation method according to claim 6, characterized in that, In step (1), the water extraction specifically involves: extracting 2-3 times, adding 5-20 times the weight of water to be extracted each time, extracting at 80°C or above for 30-120 minutes, and combining the extracts; In step (2), the extraction with ethanol solution specifically involves: extracting 2-3 times, each time adding 5-15 times the weight of the extract to be extracted with ethanol solution, wherein the ethanol solution is an aqueous solution with a volume fraction of 40%-70% ethanol, extracting at 30-50℃ or above for 30-60 minutes, and combining the extracts; In step (2), the ultrafiltration membrane is a polyethersulfone membrane or a polyvinylidene fluoride membrane with a molecular weight cutoff of 20-50 kDa.

8. The use of the traditional Chinese medicine composition according to any one of claims 1-5 in the preparation of a medicament for treating and / or preventing diabetes.

9. The application according to claim 8, characterized in that, The diabetes mellitus is lower esophageal diabetes.

10. A drug, characterized in that, Its active ingredients include the traditional Chinese medicine composition according to any one of claims 1-5.

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