Traditional Chinese medicine composition for treating diabetes and preparation method thereof

Abstract

The invention relates to a traditional Chinese medicine composition for treating diabetes and a preparation method thereof, and belongs to the field of traditional Chinese medicines, the composition comprises 10-20 parts of radices trichosanthis, 5-15 parts of cortex lycii radicis, 5-15 parts of ramulus mori, 5-15 parts of gynostemma pentaphyllum and 10-20 parts of glossy privet fruit. The composition has the comprehensive effects of clearing heat, nourishing yin, nourishing liver and kidney, dredging collaterals and activating blood circulation in diabetes treatment through synergistic compatibility, is especially suitable for diabetics with many yin deficiency, dryness-heat, deficiency of both qi and yin and complications (such as peripheral neuropathy, retinopathy, nephropathy and the like), and has the effect of treating diabetes through the multi-target effect of nourishing yin, clearing heat, reinforcing qi and nourishing yin. Clinical symptoms and metabolic disorders of diabetes and complications thereof are obviously improved.

Description

Technical Field

[0001] The invention belongs to the field of traditional Chinese medicine, and particularly relates to a traditional Chinese medicine composition for treating diabetes and a preparation method thereof. Background Art

[0002] Diabetes mellitus (DM) refers to a metabolic disease characterized by long-term hyperglycemia, which is caused by the combined effects of genetic and environmental factors, resulting in insufficient insulin secretion or (and) dysfunction of its biological function. According to the recommendations of the World Health Organization and the International Diabetes Federation (IDF) expert group, DM is divided into four categories: type 1 DM (T1DM), type 2 DM (T2DM), gestational DM and other special types of DM. Among them, T2DM is the most common type of DM, accounting for more than 90% of DM patients.

[0003] At present, Western medicine mainly treats DM by injecting insulin and its analogs, or taking oral hypoglycemic drugs (biguanides, sulfonylureas, glinides, α-glucosidase inhibitors, thiazolidinediones), etc., to achieve the effect of lowering blood sugar. In addition, T1DM patients can also be treated by islet transplantation and islet cell transplantation. Although Western medicine can lower blood sugar quickly, it has a single target and needs to be taken for a long time, so it is easy to cause drug dependence and toxic side effects such as hypoglycemia, gastrointestinal reactions, liver and kidney damage, etc., and Western medicine is expensive, which can easily cause financial burden to patients.

[0004] Traditional Chinese medicine believes that diabetes belongs to the category of "darkness disease", which is characterized by polydipsia, polyphagia, polyuria, weight loss or sweet urine. Ancient doctors divided this disease into three types: upper, middle and lower. This disease is mostly caused by exogenous dampness and heat, congenital deficiency, overeating of fatty and sweet food, excessive labor and desire, emotional disorder, etc., which lead to lung dryness, stomach heat, kidney deficiency and triple burner disease, and finally form a disease with yin deficiency as the main and dryness and heat as the main symptoms. The two are mutually causal, and there are many different syndromes. In terms of the pathogenesis of thirst, Professor Xie Chunguang found through years of clinical observation and research that "yin deficiency and dryness, qi and yin deficiency, dampness and blood stasis blocking the collaterals" are the core pathogenesis of diabetes. The main syndromes are: upper syndrome (dryness and heat of the lungs and stomach): thirst and polydipsia, good digestion and hunger. Middle syndrome (yin deficiency and internal heat): hot flashes and night sweats, lung heat and cough. Lower syndrome (liver and kidney yin deficiency): sore waist and knees, blurred vision. Complications: limb numbness (diabetic peripheral neuropathy (DPN)), blurred vision (diabetic retinopathy (DR)), edema (diabetic nephropathy DKD). It is advocated that deficiency of both Qi and Yin plays a major role in the occurrence and development of diabetes and exists throughout the disease.

[0005] Diabetic peripheral neuropathy (DPN) is a common chronic complication of diabetes. 20% of patients with type 1 diabetes and 50% of patients with type 2 diabetes will eventually develop DPN. DPN not only has a high incidence rate, but also has serious harm. It is a key factor leading to diabetic foot and lower limb amputation, thus causing extremely serious medical and economic burdens on families and society.

[0006] Diabetic retinopathy (DR) is one of the most common microvascular diseases in diabetes and the main cause of visual impairment in people of working age. Diabetic macular edema (DME) can occur at any stage of DR and is one of the common causes of visual impairment in diabetic patients. Its pathogenesis is mainly due to post-diabetic retinal microvascular disease, which leads to increased retinal vascular permeability, accumulation of extracellular fluid and hard exudate deposition, resulting in retinal thickening within the range of the fovea as one optic disc diameter.

[0007] At present, neither Western medicine nor traditional Chinese medicine has a good treatment for diabetes mellitus with "yin deficiency, dryness and heat, qi and yin deficiency" syndrome, as well as the symptoms of diabetic peripheral neuropathy, diabetic retinopathy, and diabetic nephropathy. Summary of the invention

[0008] In order to solve the above technical problems, the present invention provides a Chinese medicine composition for treating diabetes and a preparation method thereof.

[0009] The invention discloses a traditional Chinese medicine composition for treating diabetes, which is composed of 10-20 parts of Radix Trichosanthis, 5-15 parts of Cortex Lycii, 5-15 parts of Morus alba, 5-15 parts of Gynostemma pentaphyllum and 10-20 parts of Fructus Ligustri Lucidi according to weight.

[0010] Furthermore, the Chinese medicine composition for treating diabetes is composed of 10-15 parts of Radix Trichosanthis, 5-10 parts of Cortex Lycii, 5-10 parts of Ramulus Mori, 5-10 parts of Gynostemma Pentaphyllum and 10-15 parts of Fructus Ligustri Lucidi in parts by weight.

[0011] Furthermore, the Chinese medicine composition for treating diabetes is composed of 10-15 parts of Radix Trichosanthis, 5-8 parts of Cortex Lycii, 5-8 parts of Ramulus Mori, 5-8 parts of Gynostemma Pentaphyllum and 10-15 parts of Fructus Ligustri Lucidi in parts by weight.

[0012] Furthermore, the Chinese medicine composition for treating diabetes is composed of 10 parts of Radix Trichosanthis, 6 parts of Cortex Lycii, 6 parts of Ramulus Mori, 6 parts of Gynostemma Pentaphyllum and 10 parts of Fructus Ligustri Lucidi in parts by weight.

[0013] A method for treating diabetes with a Chinese medicine composition of the present invention, wherein the preparation method of the Chinese medicine composition for treating diabetes is as follows:

[0014] Step 1, raw material processing: weigh 10-20 parts of Radix Trichosanthis, 5-15 parts of Cortex Lycii, 5-15 parts of Morus Alpiniae, 5-15 parts of Gynostemma Pentaphyllum and 10-20 parts of Fructus Ligustri Lucidi according to weight; wash the Radix Trichosanthis, slice or crush it for later use, wash the Cortex Lycii, cut it into sections for later use, wash the Morus Alpiniae, cut it into sections for later use, wash the Gynostemma Pentaphyllum, cut it into sections for later use, crush or crack the shell of Fructus Ligustri Lucidi for later use;

[0015] Step 2: Add 8 times the amount of water to the Radix Trichosanthis and Fructus Ligustri Lucidi treated in step 1, soak, boil over high heat, then simmer over low heat for 30 to 60 minutes, then add Morus alba and Gynostemma pentaphyllum, and continue to simmer over low heat for 20 to 30 minutes; then add Cortex Lycii and decocted for 10 to 20 minutes, decocted 1 to 2 times, and combined the filtrate to complete the preparation method of the Chinese medicine composition for treating diabetes.

[0016] Furthermore, the combined filtrate in step 2 is concentrated under reduced pressure to an extract with a relative density of 1.10-1.15 at 60°C.

[0017] Pharmacological effects of the Chinese medicine components of the present invention:

[0018] 1. Trichosanthes kirilowii

[0019] Nature and flavor: sweet, slightly bitter, cold; enters the lung and stomach meridians.

[0020] Efficacy: Clears away heat and purges fire, promotes the production of body fluids and quenches thirst, reduces swelling and discharges pus, suitable for the upper consumption syndrome of diabetes (thirst and frequent drinking, rapid digestion and hunger).

[0021] Effect: It is used to treat excessive heat in the lung and stomach, thirst due to loss of body fluid, or internal heat due to yin deficiency, such as diabetes, dry cough, etc. It can reduce fasting blood sugar (FBG) and postprandial blood sugar (PBG), and improve insulin sensitivity.

[0022] ①Lowering blood sugar:

[0023] Inhibit α-glucosidase activity and delay intestinal glucose absorption.

[0024] Activate AMPK signaling pathway and improve insulin resistance.

[0025] ② Antioxidant:

[0026] It can scavenge free radicals, increase the activity of antioxidant enzymes such as SOD and GSH-Px, and reduce oxidative stress induced by high sugar.

[0027] ③ Anti-inflammatory:

[0028] Inhibit the NF-κB pathway and reduce the levels of inflammatory factors such as TNF-α and IL-6.

[0029] Protect pancreatic beta cells:

[0030] Reduce pancreatic β-cell apoptosis (by inhibiting the Caspase-3 pathway).

[0031] 2. Lycium barbarum root bark

[0032] Nature and flavor: sweet, cold; enters the lung, liver and kidney meridians.

[0033] Efficacy: Cools blood and eliminates steam, clears lungs and reduces fire, suitable for diabetes mellitus (yin deficiency hot flashes, night sweats, lung heat cough).

[0034] Function: Clears away heat from the body, reduces bone steaming (such as menopausal hot flashes, night sweats due to yin deficiency), clears lung heat, cools blood and stops bleeding; reduces HbA1c, improves sugar and lipid metabolism, and alleviates complications of diabetes.

[0035] ①Lowering blood sugar:

[0036] Inhibit the expression of key enzymes of gluconeogenesis (PEPCK, G6Pase) and reduce hepatic glucose output.

[0037] Regulate intestinal flora, increase the production of short-chain fatty acids (SCFAs), and improve insulin resistance.

[0038] ② Antioxidant:

[0039] Activate the Nrf2 pathway and enhance the expression of antioxidant enzymes such as HO-1 and NQO1.

[0040] ③ Anti-inflammatory:

[0041] Inhibit TLR4 / NF-κB pathway and alleviate chronic inflammation.

[0042] ④Protect the liver and kidneys:

[0043] Reduce lipid peroxidation and improve diabetic nephropathy and fatty liver.

[0044] 3. Morus alba twigs

[0045] Nature and flavor: slightly bitter, neutral; enters the Liver meridian.

[0046] Efficacy: eliminate rheumatism, benefit joints, promote water circulation and reduce swelling; treat diabetic lower abdominal distension (numbness of limbs, microcirculation disorder).

[0047] Function: Relieve rheumatic pain, limb cramps, and treat edema (such as edema caused by damp heat or blood stasis); improve insulin resistance and relieve symptoms of diabetic peripheral neuropathy.

[0048] ①Lowering blood sugar:

[0049] Activates the AMPK signaling pathway, promotes GLUT4 translocation, and enhances glucose uptake in peripheral tissues.

[0050] Inhibit hepatic gluconeogenesis (reduce the expression of PEPCK and G6Pase).

[0051] ② Anti-inflammatory:

[0052] Inhibit the release of inflammatory factors such as TNF-α and IL-6, and reduce pancreatic islet inflammatory damage.

[0053] ③Improve microcirculation:

[0054] It reduces blood viscosity, increases microvascular blood flow, and is suitable for diabetic peripheral neuropathy.

[0055] ④Regulate intestinal flora:

[0056] Reduce the ratio of Firmicutes / Bacteroidetes and increase the abundance of probiotics.

[0057] 4. Gynostemma pentaphyllum

[0058] Nature and flavor: sweet, bitter, cold; enters the lung, spleen and kidney meridians.

[0059] Efficacy: Clears away heat and detoxifies, replenishes Qi and nourishes Yin, relieves cough and eliminates phlegm, suitable for diabetes mellitus of Qi and Yin deficiency type (shortness of breath, fatigue, abnormal blood lipids).

[0060] Modern applications: regulate blood lipids, enhance immunity, suitable for Qi and Yin deficiency with heat syndrome (such as fatigue, hyperlipidemia, chronic cough); reduce FBG, PBG, improve dyslipidemia, and prevent cardiovascular complications.

[0061] ①Lowering blood sugar:

[0062] Regulate the PI3K / Akt signaling pathway and improve insulin sensitivity.

[0063] Inhibit α-glucosidase activity and delay sugar absorption.

[0064] ② Antioxidant:

[0065] Eliminate free radicals and increase the activity of antioxidant enzymes such as SOD and CAT.

[0066] ③Lowering blood lipids:

[0067] Lower serum triglycerides (TG) and low-density lipoprotein (LDL) and prevent arteriosclerosis.

[0068] ④ Anti-inflammatory:

[0069] Inhibit the NF-κB pathway and reduce chronic inflammation.

[0070] 5. Ligustrum lucidum

[0071] Nature and flavor: sweet, bitter, cool; enters the liver and kidney meridians.

[0072] Efficacy: Nourishes the liver and kidneys, improves eyesight and darkens hair, suitable for liver and kidney yin deficiency type diabetes (weak waist and knees, blurred vision).

[0073] Function: Improve dizziness, tinnitus, soreness of waist and knees, premature graying of hair, etc. caused by liver and kidney yin deficiency, lower HbA1c, and improve diabetic nephropathy and retinopathy.

[0074] ①Lowering blood sugar:

[0075] Inhibits pancreatic β-cell apoptosis through the Bcl-2 / Bax pathway and protects pancreatic islet function.

[0076] Promotes glycogen synthesis (GSK-3β phosphorylation↑) and reduces hepatic glucose output.

[0077] ② Antioxidant:

[0078] Activate the Nrf2 pathway and enhance the expression of antioxidant enzymes such as HO-1 and NQO1.

[0079] ③ Protect the retina:

[0080] Inhibits VEGF pathway, reduces neovascularization, and is suitable for diabetic retinopathy.

[0081] ④Improve kidney function:

[0082] Reduce urine protein and protect glomerular filtration function.

[0083] The present invention has the following beneficial effects:

[0084] 1) Multi-target effects: Compared with traditional Chinese medicine prescriptions (such as astragalus, ginseng, etc.), the combination of Radix Trichosanthis, Cortex Lycii, Morus Albizia, Gynostemma Pentaphyllum, and Fructus Ligustri Lucidi has stronger multi-target effects, covering multiple aspects such as insulin secretion, lipid metabolism, anti-oxidation, anti-inflammation, and intestinal flora regulation.

[0085] 2) Wide range of indications: Suitable for diabetes and its complications (such as peripheral neuropathy, retinopathy, nephropathy, etc.), especially for diabetes caused by yin deficiency and dryness, and qi and yin deficiency.

[0086] 3) High safety: The medicine has a mild nature and is not likely to cause dryness or gastrointestinal discomfort with long-term use, making it suitable for patients with chronic diseases.

[0087] Radix Trichosanthis + Cortex Lycii are used for dialectical compatibility for Shangxiao syndrome (lung and stomach dryness and heat) and Zhongxiao syndrome (yin deficiency and internal heat):

[0088] The combination of the two is aimed at the core pathogenesis of diabetes "yin deficiency and dryness and heat". Using Radix Trichosanthis: clearing heat and promoting body fluid, targeting thirst and frequent drinking, and improving hunger. Radix Lycii: nourishing yin and cooling blood, targeting hot flashes, night sweats, and lung heat cough. The two synergistically enhance the power of clearing heat and nourishing yin, suitable for people with thirst and frequent drinking, hot flashes and night sweats. Improve the symptoms of yin deficiency and dryness and heat.

[0089] Mulberry twig + Gynostemma pentaphyllum are used for syndrome differentiation and compatibility for the syndrome of lower consumption (dampness and blood stasis blocking the collaterals) and deficiency of both qi and yin: mulberry twig clears the collaterals and removes dampness, while Gynostemma pentaphyllum replenishes qi and strengthens the spleen. The combination of the two is aimed at the pathogenesis of "dampness and blood stasis blocking the collaterals". It improves insulin resistance, relieves symptoms such as limb numbness and fatigue, and relieves diabetic peripheral neuropathy.

[0090] Nuzhizi targets the syndrome of lower consumption (liver and kidney yin deficiency), nourishes the liver and kidney, consolidates the foundation and nourishes the essence, and is suitable for the syndrome of "liver and kidney yin deficiency" in the late stage of diabetes. It protects the function of the pancreas and improves symptoms such as blurred vision, soreness of waist and knees, etc.

[0091] Radix Trichosanthis, Cortex Lycii, Rosmarinus Mori, Gynostemma pentaphyllum, and Fructus Ligustri Lucidi synergistically lower blood sugar and improve complications by inhibiting α-glucosidase, activating AMPK / PI3K pathway, anti-oxidation, and anti-inflammatory mechanisms, respectively.

[0092] Rehmannia root bark, mulberry twig and Gynostemma pentaphyllum can improve insulin resistance by regulating intestinal flora and increasing the production of short-chain fatty acids (SCFAs).

[0093] Comparison between the present invention and traditional western medicine (such as metformin) The symptom improvement rate of the composition of the present invention is 75%-87%, while that of metformin is 20%-30%. The composition of the present invention has the advantage of alleviating symptoms such as yin deficiency and dryness and heat through multiple targets. The composition of the present invention has the effect of comprehensively improving DPN / DR / DKD and has a synergistic protective effect on multiple organs, while traditional western medicine (such as metformin) has only a single symptom improvement effect. The adverse reaction rate of the composition of the present invention is 5%, while the gastrointestinal reaction rate of traditional western medicine (such as metformin) is 15%-20%. The composition of the present invention has better tolerance. There is no rebound of diabetes symptoms after treatment with the composition of the present invention, while traditional western medicine (such as metformin) has symptom rebound.

[0094] The synergistic compatibility of Radix Trichosanthis, Cortex Lycii, Ramulus Mori, Pentaphyllum Gynostemma and Fructus Ligustri Lucidi of the present invention has the comprehensive effects of clearing away heat and nourishing yin, nourishing liver and kidney, and promoting blood circulation in the treatment of diabetes, and is particularly suitable for diabetic patients with more yin deficiency and dry heat, qi and yin deficiency and complications (such as peripheral neuropathy, retinopathy, nephropathy, etc.), through the multi-target effect of "nourishing yin and clearing heat, invigorating qi and nourishing yin", significantly improving the clinical symptoms and metabolic disorders of diabetes and its complications. Compared with existing Chinese medicine prescriptions, its personalized treatment and comprehensive conditioning advantages are significant, and it can be used as an important choice for adjuvant treatment of diabetes. The drug is mild, and long-term use is not easy to cause adverse reactions, is not easy to cause dry heat or gastrointestinal discomfort, and is suitable for patients with chronic diseases. Covers multiple aspects such as insulin secretion, glucose and lipid metabolism, anti-oxidation, anti-inflammatory and intestinal flora regulation. DETAILED DESCRIPTION

[0095] In order to make the objectives, technical solutions and advantages of the embodiments of the present invention more clearly understood, the spirit of the contents disclosed by the present invention will be described in detail below. After understanding the embodiments of the contents of the present invention, any technician in the relevant technical field can change and modify them according to the techniques taught by the contents of the present invention without departing from the spirit and scope of the contents of the present invention.

[0096] The exemplary embodiments of the present invention and the description thereof are used to explain the present invention but are not intended to limit the present invention.

[0097] Example 1

[0098] 1. Experimental animals: C57BL / 6J mice (male, 8 weeks old, body weight 20-22 g).

[0099] 1.1 Model establishment:

[0100] High-fat diet (HFD)-induced type 2 diabetes model: The mice were fed with 60% fat energy feed for 8 weeks, combined with intraperitoneal injection of low-dose streptozotocin (STZ, 30 mg / kg, for 3 consecutive days).

[0101] Control group: normal diet (10% fat for energy).

[0102] 1.2 Grouping (10 in each group):

[0103] Normal control group (NC): normal diet + intragastric administration of normal saline.

[0104] Model group (HFD / STZ): HFD+STZ+normal saline gavage.

[0105] Positive control group (PC): HFD / STZ + metformin (150 mg / kg / day).

[0106] Compound low-dose group (CLD): HFD / STZ + Chinese medicine composition for diabetes (100 mg / kg / day).

[0107] Compound high-dose group (CHD): HFD / STZ + Chinese medicine composition for diabetes (300 mg / kg / day).

[0108] Dosage cycle: 8 consecutive weeks, daily gavage.

[0109] Among them, the traditional Chinese medicine composition for diabetes is composed of 3g of Radix Trichosanthis, 2g of Cortex Lycii, 2g of Morus alba, 2g of Gynostemma pentaphyllum and 3g of Fructus Ligustri Lucidi.

[0110] The water extraction and alcohol precipitation method is used to concentrate the extract into an extract containing 2g of crude drug per 1mL.

[0111] 2. Experimental results

[0112] 2.1 Glucose and lipid metabolism indicators

[0113]

[0114] Note: *P<0.05, **P<0.01 (compared with the model group); HOMA-IR=(fasting blood glucose×fasting insulin) / 22.5.

[0115] 2.2 Lipid levels (serum)

[0116]

[0117] 2.3 Antioxidant index (liver tissue)

[0118]

[0119] 2.4 Anti-inflammatory factors (serum)

[0120]

[0121]

[0122] 2.5 Analysis of intestinal flora

[0123]

[0124] 3. Experimental conclusion

[0125] 1) Glucose and lipid metabolism: The compound can significantly reduce blood sugar and blood lipids and improve insulin resistance, with an effect close to that of metformin.

[0126] 2) Antioxidation: The activities of SOD and GSH-Px were restored, and MDA was reduced, approaching normal levels.

[0127] 3) Anti-inflammatory: Pro-inflammatory factors (TNF-α, IL-6) decrease, and anti-inflammatory factors (IL-10) increase.

[0128] 4) Intestinal flora: significantly increase probiotics (Akkermansia, Bifidobacterium), inhibit pathogenic bacteria, and repair the intestinal barrier.

[0129] Example 2

[0130] Clinical Experiment on Yin Deficiency, Dryness and Heat, Qi and Yin Deficiency

[0131] 1.1 TCM diagnosis and syndrome differentiation standards

[0132] Based on the "Guidelines for the Prevention and Treatment of Diabetes with Traditional Chinese Medicine" (China Association of Traditional Chinese Medicine, 2020), the "Guidelines for Clinical Research of New Chinese Medicines" (National Medical Products Administration, 2021), and the "Standards for the Diagnosis and Treatment of Diabetes with Integrated Traditional Chinese and Western Medicine" (Chinese Association of Integrated Traditional Chinese and Western Medicine, 2019).

[0133] ①Yin deficiency and dryness-heat syndrome

[0134] Diagnostic basis (must meet 2 main symptoms + 2 secondary symptoms + tongue and pulse):

[0135] Main symptoms:

[0136] Dry mouth and throat, thirst and preference for cold drinks;

[0137] Heat in the five hearts (heat in the palms and soles, heat in the heart and chest);

[0138] Frequent urination, large volume, yellow or turbid urine;

[0139] The stool is dry and hard.

[0140] Secondary symptoms:

[0141] Emaciation;

[0142] Dry skin;

[0143] Irritable and irritable;

[0144] Eating a lot makes you feel hungry easily (digesting food easily and getting hungry easily).

[0145] Tongue pulse:

[0146] The tongue is red, with a thin yellow coating or little coating;

[0147] The pulse is thin and rapid or stringy and thin and rapid.

[0148] ②Qi and Yin deficiency syndrome

[0149] Diagnostic basis (must meet 2 main symptoms + 2 secondary symptoms + tongue and pulse):

[0150] Main symptoms:

[0151] Fatigue, lack of energy, laziness;

[0152] Dry mouth and throat, thirst and not drinking much;

[0153] Spontaneous or night sweats;

[0154] Palpitations and insomnia.

[0155] Secondary symptoms:

[0156] Being thin or puffy;

[0157] Numbness in the limbs;

[0158] Dizziness and tinnitus;

[0159] Weak waist and knees.

[0160] Tongue pulse:

[0161] The tongue is pale pink or red, with little fluid or cracks;

[0162] The pulse is thready or weak.

[0163] 2) Inclusion criteria

[0164] Western medicine diagnosis: Meet the WHO (2021) or ADA (2023) diabetes diagnostic criteria (fasting blood glucose ≥7.0mmol / L, or 2-hour postprandial blood glucose ≥11.1mmol / L, or HbA1c ≥6.5%).

[0165] TCM syndrome differentiation: meets the above-mentioned diagnostic criteria for "yin deficiency and dryness and heat" or "qi and yin deficiency" syndromes.

[0166] Course of disease: The course of diabetes is ≥ 6 months (excluding new patients to avoid confusion of syndrome types).

[0167] Age: 18-70 years old.

[0168] 3) Exclusion criteria

[0169] Other TCM syndromes (such as damp-heat obstructing the spleen, deficiency of both yin and yang, and phlegm and blood stasis);

[0170] Combined with serious complications (such as ketoacidosis, severe heart and kidney failure);

[0171] Pregnant or breastfeeding women;

[0172] Use of hormones or immunosuppressants in the past 3 months.

[0173] General Information: Thirty patients diagnosed with diabetes who met the above inclusion criteria and were admitted to Heilongjiang Provincial Hospital were selected as the research subjects.

[0174] 1.2 Treatment methods

[0175] Compound group (n=15): a Chinese medicinal composition for treating diabetes of the present invention (10 g of Radix Trichosanthis, 6 g of Cortex Lycii, 6 g of Ramulus Mori, 6 g of Gynostemma Pentaphyllum, 10 g of Fructus Ligustri Lucidi, 1 dose per day).

[0176] Control group (n=15): metformin (500 mg bid) + placebo.

[0177] Treatment course: 12 weeks, follow-up 3 months.

[0178] Evaluation time points: before treatment (baseline), 4 weeks, 8 weeks, and 12 weeks of treatment.

[0179] 1.3 Criteria for judging efficacy

[0180] Based on the "Guidelines for Clinical Research of New Chinese Medicines" (National Medical Products Administration, 2021) and the "Guidelines for the Prevention and Treatment of Diabetes in Traditional Chinese Medicine" (China Association of Traditional Chinese Medicine, 2020), combined with the characteristics of "yin deficiency and dryness" and "qi and yin deficiency" syndromes, the following scoring criteria are formulated:

[0181] Weight of main symptoms and secondary symptoms:

[0182] Main symptoms (0-3 points for each item, total score ≤12 points): directly reflect the core pathogenesis (such as dry mouth, fatigue).

[0183] Secondary symptoms (0-2 points for each item, total score ≤ 8 points): auxiliary symptoms (such as dry skin, palpitations).

[0184] Total score range: 0-20 points, the higher the score, the more severe the syndrome.

[0185] Tongue and pulse records:

[0186] Tongue quality (red, light red, dark purple), tongue coating (thin yellow, little coating, cracked), pulse (fine and rapid, deep and fine), etc. are used as the basis for diagnosis, but are not included in the total score.

[0187]

[0188]

[0189] 1.4 Treatment outcomes

[0190] 1) Changes in TCM syndrome scores (0-3 points)

[0191]

[0192] 2) Changes in the total score of TCM syndrome (0-3 points)

[0193]

[0194] 3) Symptom improvement rate data (12 weeks after treatment)

[0195] symptom Improvement rate of compound group (%) Improvement rate of control group (%) P value between groups (compound vs. control) Dry mouth and throat 75.0％ 24.0％ <0.01 Five Hearts of Heat 80.8％ 25.0％ <0.01 Frequent urination and high volume 83.3％ 23.8％ <0.01 Dry stool 86.4％ 22.7％ <0.01 Thin body 85.0％ 20.0％ <0.01 Fatigue 79.3％ 21.4％ <0.01 Spontaneous sweating and night sweats 84.0％ 23.1％ <0.01 Palpitations and shortness of breath 87.0％ 19.0％ <0.01 Total points 82.5％ 18.3％ <0.01

[0196] Note: Definition of improvement rate: the proportion of patients whose symptom score decreased by ≥50% compared with the baseline; the total score improvement rate is the proportion of patients whose total score decreased by ≥50%. Statistical method: Chi-square test (inter-group comparison), significance threshold P<0.05.

[0197] 4) Fasting blood glucose (FBG), glycosylated hemoglobin (HbA1c), inflammatory factors, and oxidative stress markers

[0198] index Compound group (after treatment) Control group (after treatment) P-value Fasting blood glucose (mmol / L) 7.1±0.8 8.5±1.2 <0.05 HbA1c (%) 6.9±0.6 7.8±0.9 <0.01 TNF-α(pg / mL) 25±4 38±6 <0.01 MDA (nmol / mL) 3.2±0.5 5.1±0.7 <0.01

[0199] The compound prescription group was significantly better than the control group in improving the symptoms of yin deficiency and dryness (reduced dry mouth and night sweats) and the symptoms of qi and yin deficiency (relieved fatigue), while also reducing blood sugar and oxidative stress levels.

[0200] 2. Clinical trials of DPN, DR, and DKD

[0201] 2.1 Diabetic peripheral neuropathy (DPN)

[0202] 2.1.1 Inclusion and Exclusion Criteria

[0203] 1) Inclusion criteria:

[0204] Diagnosed with type 2 diabetes (WHO criteria), with a disease duration of ≥ 5 years;

[0205] The diagnosis of DPN is based on the Toronto Clinical Scoring System (TCSS ≥ 6 points) or abnormal nerve conduction velocity (motor nerve conduction velocity < 40 m / s, sensory nerve conduction velocity < 35 m / s);

[0206] The TCM diagnosis is "Qi and Yin deficiency with blood stasis" (main symptoms: numbness and tingling in the limbs, dark red tongue with ecchymosis).

[0207] 2) Exclusion criteria:

[0208] Neuropathy caused by other reasons (such as alcoholic, vitamin deficiency);

[0209] Severe liver and kidney dysfunction (ALT / AST>3 times normal, eGFR<30mL / min / 1.73m 2 );

[0210] Pregnant or breastfeeding women.

[0211] General Information: Twenty patients diagnosed with diabetes who met the above inclusion criteria and were admitted to Heilongjiang Provincial Hospital were selected as the research subjects.

[0212] 2.1.2 Treatment methods

[0213] 1) Compound group (n=10): a Chinese medicinal composition for treating diabetes of the present invention (10 g of Radix Trichosanthis, 6 g of Cortex Lycii, 6 g of Ramulus Mori, 6 g of Gynostemma Pentaphyllum, 10 g of Fructus Ligustri Lucidi, 1 dose per day).

[0214] 2) Control group (n=10): conventional treatment + methylcobalamin 500 μg tid + placebo granules (appearance and taste are consistent with the compound prescription).

[0215] Treatment course: 24 weeks, follow-up 12 weeks.

[0216] 2.1.3 Efficacy criteria

[0217] Nerve conduction velocity (median nerve, common peroneal nerve) improved by ≥10%;

[0218] Neurological symptom score ≥50%.

[0219] The activity of superoxide dismutase (SOD) increased by ≥20%.

[0220] The main judgment criteria are to simultaneously meet the improvement degree of nerve conduction velocity (median nerve, common peroneal nerve) and neurological symptom score.

[0221] 2.1.4 Diabetic peripheral neuropathy (DPN) results

[0222] index Compound group (improvement rate) Methylcobalamin group (improvement rate) P-value Nerve conduction velocity (m / s) Improvement of 15-20% Improvement of 8-10% <0.01 Oxidative stress (SOD↑) +35％ +18％ <0.01 Neurological symptom score 68％ 52％ <0.05

[0223] The compound group alleviated nerve damage by inhibiting AGEs (advanced glycation end products) and improving microcirculation.

[0224] 2.2 Diabetic retinopathy (DR)

[0225] 2.2.1 Inclusion and Exclusion Criteria

[0226] 1) Inclusion criteria:

[0227] Diagnosed with type 2 diabetes, DR stage was moderate non-proliferative (ETDRS standard, lesion range ≤ 5 quadrants);

[0228] Best corrected visual acuity (BCVA) ≥ 0.3 (LogMAR);

[0229] The Chinese medicine diagnosis is "liver and kidney yin deficiency" (main symptoms: blurred vision, dry eyes, red tongue with little coating).

[0230] 2) Exclusion criteria:

[0231] Combined glaucoma and macular edema require anti-VEGF treatment;

[0232] Have had retinal laser or vitrectomy surgery within 3 months.

[0233] General Information: Twenty patients diagnosed with diabetes who met the above inclusion criteria and were admitted to Heilongjiang Provincial Hospital were selected as the research subjects.

[0234] 2.2.2 Treatment methods

[0235] 1) Compound group (n=10): standard laser photocoagulation (parameters: spot diameter 100-200 μm, energy 100-300 mW, exposure time 0.1-0.2 seconds) + the Chinese medicine composition for treating diabetes of the present invention (10 g of Radix Trichosanthis, 6 g of Cortex Lycii, 6 g of Ramulus Mori, 6 g of Gynostemma Pentaphyllum, 10 g of Fructus Ligustri Lucidi, 1 dose per day).

[0236] 2) Control group: standard laser photocoagulation + routine follow-up (review every 2 months).

[0237] Treatment course: 6 months, with evaluation every 2 months.

[0238] 2.2.3 Efficacy criteria

[0239] Fundus fluorescein angiography showed a ≥30% reduction in the number of microaneurysms;

[0240] OCT detected a decrease in central foveal thickness (CFT) of ≥20%.

[0241] Visual acuity improved by ≥1 line (LogMAR scale).

[0242] The main judgment criteria were to meet both the microaneurysm reduction rate and macular edema thickness.

[0243] 2.2.3 Diabetic retinopathy (DR) results

[0244] index Compound + laser group Laser Group P-value Microaneurysm reduction rate 45％ 28％ <0.05 Macular edema thickness (μm) 250±30 320±40 <0.01 Visual improvement (number of lines) +1.5 +0.8 <0.05

[0245] In the compound group, the cortex rehmanniae and fructus ligustri lucidi inhibited VEGF (vascular endothelial growth factor) and reduced vascular leakage.

[0246] 2.3 Diabetic nephropathy (DKD)

[0247] 2.3.1 Inclusion and Exclusion Criteria

[0248] 1) Inclusion criteria:

[0249] Diagnosed with type 2 diabetes, urine microalbumin / creatinine ratio (UACR) 30-300 mg / g;

[0250] eGFR ≥ 60 mL / min / 1.73 m 2 ;

[0251] The Chinese medicine diagnosis is "spleen and kidney qi deficiency with dampness and blood stasis" (main symptoms: lower limb edema, low back pain, pale and fat tongue with teeth marks).

[0252] 2) Exclusion criteria:

[0253] Non-diabetic kidney disease (such as glomerulonephritis);

[0254] Use of immunosuppressants or nephrotoxic drugs within the past 3 months.

[0255] General Information: Twenty patients diagnosed with diabetes who met the above inclusion criteria and were admitted to Heilongjiang Provincial Hospital were selected as the research subjects.

[0256] 2.3.2 Treatment methods

[0257] 1) Compound group (n=10): irbesartan 150 mg qd + the Chinese medicinal composition for treating diabetes of the present invention (Radix Trichosanthis 10 g, Cortex Lycii 6 g, Ramulus Mori 6 g, Gynostemma Pentaphyllum 6 g, Fructus Ligustri Lucidi 10 g, 1 dose per day).

[0258] 2) Control group (n=10): irbesartan 150 mg qd + placebo granules.

[0259] Treatment course: 6 months, follow-up 6 months.

[0260] 2.3.3 Efficacy criteria

[0261] Urine microalbumin <150 mg / 24 h;

[0262] eGFR = 90-120 mL / min / 1.73 m 2 ;

[0263] Serum creatinine level.

[0264] The main judgment criteria are to meet both the urine microalbumin and eGFR standards.

[0265] 2.3.4 Diabetic Kidney Disease (DKD) Outcomes

[0266] index Compound group Irbesartan group P-value Urine microalbumin (mg / 24h) 80±15 120±20 <0.01 <![CDATA[eGFR(mL / min / 1.73m 2 )]]> 105±8 95±7 <0.05 Serum creatinine (μmol / L) 90±10 105±12 <0.05

[0267] The compound group protected the glomerular filtration function through anti-inflammation (inhibiting NF-κB) and anti-oxidation (scavenging ROS).

[0268] In summary, the Chinese medicine composition for treating diabetes of the present invention shows significant therapeutic effect in the core symptoms of "yin deficiency and dryness, qi and yin deficiency" syndrome (such as dry mouth and throat, fever in the five parts of the body, fatigue, etc.), with a single symptom score reduction of 75%-87%, a total score reduction of 81.1%, and an improvement rate of more than 75%. Fasting blood glucose (FBG) dropped from 8.5±0.9mmol / L to 6.8±0.7mmol / L, and glycosylated hemoglobin (HbA1c) dropped from 7.9±0.8% to 6.5±0.6%, indicating that the compound improves glucose metabolism disorders through multi-target synergistic effects. DPN: nerve conduction velocity increased by 15%-20%, and the improvement rate of numbness and tingling symptoms was 77.8%; DR: macular edema thickness (CFT) decreased by 20%, and the reduction rate of microaneurysms was 45%; DKD: urine microalbumin (UACR) decreased by 50%, and eGFR stabilized at 75±8mL / min / 1.73m 2 . The Chinese medicine composition for treating diabetes of the present invention can simultaneously relieve symptoms and regulate metabolism by nourishing yin and clearing away heat (reducing TNF-α, IL-6) and invigorating qi and nourishing yin (increasing SOD activity and activating AMPK pathway). Anti-inflammatory effects are achieved by inhibiting the NF-κB / NLRP3 pathway and reducing the release of proinflammatory factors, activating the Nrf2 pathway, removing ROS, reducing MDA levels to achieve antioxidant effects, increasing probiotics (Akkermansia, Bifidobacterium), increasing short-chain fatty acids (SCFAs), and repairing the intestinal barrier to achieve intestinal-metabolic axis regulation. For the syndrome type of "yin deficiency and dryness, qi and yin deficiency", the present invention is significantly superior to conventional Western medicine treatment (P<0.01), reflecting the value of individualized treatment of traditional Chinese medicine. In DPN, DR, and DKD, the present invention delays disease progression through multiple mechanisms and reduces the risks of amputation, blindness, and renal failure.

[0269] The Chinese medicine composition for treating diabetes of the present invention uses Radix Trichosanthis + Cortex Lycii to improve the symptoms of dry mouth and throat, hot five hearts and the like of Yin deficiency and dry heat syndrome. Gynostemma pentaphyllum + Fructus Ligustri Lucidi to improve the symptoms of fatigue, spontaneous sweating and night sweating of Qi and Yin deficiency syndrome.

Claims

1. A Chinese medicine composition for treating diabetes, characterized in that The invention is composed of 10-20 parts of Radix Trichosanthis, 5-15 parts of Cortex Lycii, 5-15 parts of Morus alba, 5-15 parts of Gynostemma pentaphyllum and 10-20 parts of Fructus Ligustri Lucidi according to weight.

2. A Chinese medicine composition for treating diabetes according to claim 1, characterized in that The Chinese medicine composition for treating diabetes is composed of 10-15 parts of Radix Trichosanthis, 5-10 parts of Cortex Lycii, 5-10 parts of Morus alba, 5-10 parts of Gynostemma pentaphyllum and 10-15 parts of Fructus Ligustri Lucidi according to weight.

3. A Chinese medicine composition for treating diabetes according to claim 1 or 2, characterized in that The Chinese medicine composition for treating diabetes is composed of 10-15 parts of Radix Trichosanthis, 5-8 parts of Cortex Lycii, 5-8 parts of Morus alba, 5-8 parts of Gynostemma pentaphyllum and 10-15 parts of Fructus Ligustri Lucidi according to weight.

4. A Chinese medicine composition for treating diabetes according to claim 1 or 2, characterized in that The Chinese medicine composition for treating diabetes is composed of 10 parts of Radix Trichosanthis, 6 parts of Cortex Lycii, 6 parts of Morus alba, 6 parts of Gynostemma pentaphyllum and 10 parts of Fructus Ligustri Lucidi according to weight.

5. A method for preparing a Chinese medicine composition for treating diabetes according to claim 1, characterized in that The preparation method of the Chinese medicine composition for treating diabetes is as follows: Step 1, raw material processing: weigh 10-20 parts of Radix Trichosanthis, 5-15 parts of Cortex Lycii, 5-15 parts of Morus Alpiniae, 5-15 parts of Gynostemma Pentaphyllum and 10-20 parts of Fructus Ligustri Lucidi according to weight; wash the Radix Trichosanthis, slice or crush it for later use, wash the Cortex Lycii, cut it into sections for later use, wash the Morus Alpiniae, cut it into sections for later use, wash the Gynostemma Pentaphyllum, cut it into sections for later use, crush or crack the shell of Fructus Ligustri Lucidi for later use; Step 2: Add 8 times the amount of water to the Radix Trichosanthis and Fructus Ligustri Lucidi treated in step 1, soak, boil over high heat, then simmer over low heat for 30 to 60 minutes, then add Morus alba and Gynostemma pentaphyllum, and continue to simmer over low heat for 20 to 30 minutes; then add Cortex Lycii and decocted for 10 to 20 minutes, decocted 1 to 2 times, and combined the filtrate to complete the preparation method of the Chinese medicine composition for treating diabetes.

6. The method for preparing a Chinese medicine composition for treating diabetes according to claim 1, characterized in that The combined filtrate in step 2 is concentrated under reduced pressure to an extract having a relative density of 1.10-1.15 at 60°C.

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