Application of traditional Chinese medicine composition in preparation of medicine for treating diabetes or diabetes-related diseases

Abstract

The invention relates to application of a traditional Chinese medicine composition in preparation of a medicine for treating diabetes or diabetes-related diseases. The composition is prepared from the following raw material medicines and optional pharmaceutically acceptable auxiliary materials: radix rehmanniae recen, cortex moutan, radix arnebiae seu lithospermi, radix paeoniae rubra, flos lonicerae, herba hedyotidis diffusae, rhizoma smilacis glabrae, herba artemisiae scopariae, raw flos sophorae, raw pollen typhae, indigo naturalis, pericarpium citri reticulatae and fructus crataegi. The traditional Chinese medicine can achieve the effects of cooling blood, removing toxicity, promoting diuresis, dispersing blood stasis, nourishing yin and moistening dryness, is beneficial to improvement of diabetes and related diseases, and has good clinical application value and popularization prospect.

Description

Technical Field

[0001] This invention relates to the field of traditional Chinese medicine, specifically to the application of a traditional Chinese medicine composition in the preparation of a medicament for treating diabetes or diabetes-related diseases. Background Technology

[0002] Diabetes mellitus is a metabolic disease characterized by chronic hyperglycemia, and the number of people with the disease worldwide is rapidly increasing. According to data from the International Diabetes Federation (IDF) in 2021, there are over 537 million people with diabetes globally, and this number is projected to reach 783 million by 2045. The "Guidelines for the Prevention and Treatment of Type 2 Diabetes in China (2020)" indicates that the HbA1c target achievement rate is only around 50%. Currently, commonly used clinical drugs include metformin, insulin, and SGLT-2 inhibitors. While these can effectively lower blood sugar in the short term, long-term use can cause various adverse reactions, such as gastrointestinal irritation, hypoglycemia, urinary tract infections, and liver and kidney damage. Furthermore, these drugs are unlikely to effectively intervene in the core pathological processes of diabetes, such as insulin resistance, pancreatic β-cell dysfunction, and liver and pancreatic damage caused by glucose and lipid metabolism disorders.

[0003] Traditional Chinese medicine classifies diabetes under the category of "Xiao Ke" (wasting and thirsting syndrome), with common patterns including Yin deficiency with excessive heat, Qi and Yin deficiency, Yin and Yang deficiency, and internal damp-heat. Treatment often employs principles such as nourishing Yin and clearing heat, tonifying Qi and nourishing Yin, warming Yang and nourishing Yin, and clearing heat and resolving dampness. However, clinical observations have revealed that some diabetic patients, especially those with diabetes complicated by obesity and hyperlipidemia, present with a complex pattern of "damp-heat accumulation and internal obstruction of blood stasis and toxins." Symptoms include dry and bitter mouth, dark red tongue with ecchymosis, and thick, greasy yellow tongue coating. Traditional formulas are insufficiently targeted and have limited efficacy in treating this type of syndrome.

[0004] While researching psoriasis, the inventors unexpectedly discovered that the traditional Chinese medicine composition used had a particularly significant therapeutic effect on diabetes or diabetes-related diseases. In diabetic patients, it can regulate blood glucose metabolism, improve insulin sensitivity, and protect the pancreas. It is especially suitable for treating diabetic patients with syndromes such as "damp-heat accumulation and internal obstruction of blood stasis and toxins". This led to the completion of the present invention, which is a case of using the same formula for different diseases, in line with the traditional Chinese medicine theory of "treating different diseases with the same method". Summary of the Invention

[0005] To address the aforementioned technical problems, this invention provides the use of a traditional Chinese medicine composition in the preparation of a medicament for treating diabetes or diabetes-related diseases. The traditional Chinese medicine composition is made from the following raw materials and optional pharmaceutically acceptable excipients: Rehmannia glutinosa, Paeonia suffruticosa, Lithospermum erythrorhizon, Paeonia lactiflora, Lonicera japonica, Hedyotis diffusa, Smilax glabra, Artemisia capillaris, Sophora japonica, Typha orientalis, Indigo naturalis, Citrus reticulata peel, and Crataegus pinnatifida. The botanical names and parts used from which these raw materials originate are shown in Table 1 below.

[0006] Table 1. Plant source and part used for each active pharmaceutical ingredient

[0007]

[0008] Analysis shows that the herbal composition follows the principles of TCM syndrome differentiation and treatment and the "principal, assistant, adjuvant, and guide" formula, in its formulation.

[0009] The principal herbs include Rehmannia glutinosa and Paeonia suffruticosa, which are the core drugs for treating diabetes. Rehmannia glutinosa is sweet and cold in nature and moistens the body. It enters the heart, liver and kidney meridians, nourishes yin and generates fluids, cools the blood and moistens dryness. It effectively relieves symptoms such as thirst and excessive drinking, and five-center heat caused by yin deficiency and fluid depletion. It is a commonly used herb for treating diabetes caused by yin deficiency and internal heat. Paeonia suffruticosa is bitter and cold and enters the blood. It is good at clearing latent heat in the blood, cooling the blood and promoting blood circulation. It can directly counteract the evil of blood heat and help to dredge the blood vessels and remove blood stasis. The two herbs are used together. One clears and the other nourishes, one moistens and the other invigorates. It not only meets the core pathogenesis of "heat scorching yin and blood", but also can govern the syndrome of mixed deficiency and excess.

[0010] The assistant herbs include Lithospermum erythrorhizon, Paeonia lactiflora, Lonicera japonica, and Hedyotis diffusa; they mainly assist the principal herbs in clearing latent heat in the blood, promoting blood circulation and removing blood stasis, and eliminating toxins and dampness. Lithospermum erythrorhizon is sweet, salty, and cold in nature, clearing heat and cooling the blood, and is good at clearing heat in the blood; Paeonia lactiflora is bitter and slightly cold, clearing heat and cooling the blood, removing blood stasis and relieving pain, and works with Paeonia suffruticosa to enhance the effects of clearing heat and promoting blood circulation; Lonicera japonica clears heat and detoxifies, disperses stagnant heat, and helps to expel latent pathogens from the outside; Hedyotis diffusa is bitter and cold, clearing heat and promoting diuresis, detoxifying and eliminating carbuncles, and is good at resolving damp-heat toxins and improving various symptoms caused by internal damp-heat; the four herbs work together to enhance the effects of this formula in cooling the blood and detoxifying, promoting blood circulation and removing blood stasis, and eliminating dampness and toxins.

[0011] The adjuvant herbs include Smilax glabra, Artemisia capillaris, Sophora japonica, Typha pollen, and Indigo naturalis; these are used to enhance the effects of dispelling dampness and unblocking the meridians, cooling the blood and detoxifying, and clearing liver heat. Among them, Smilax glabra is sweet and bland in nature, dispelling dampness and detoxifying; Artemisia capillaris is bitter and cold, clearing damp-heat in the liver and gallbladder, and helping to regulate the triple burner; Sophora japonica is bitter and cold, cooling the blood and stopping bleeding, clearing liver heat, and preventing bleeding caused by blood heat; Typha pollen is neutral in nature, promoting blood circulation and removing blood stasis, and working with Paeonia suffruticosa and Paeonia lactiflora to enhance the effect of promoting blood circulation and removing blood stasis; Indigo naturalis is salty and cold, clearing heat and detoxifying. The five herbs work together to deeply harmonize Qi and blood, clear damp-heat, and assist the overall treatment plan in better regulating the multifactorial pathological state of diabetes.

[0012] The herbs tangerine peel and hawthorn are used to harmonize the middle jiao (middle burner) and aid the spleen and stomach, thereby promoting the absorption and transformation of the medicine. Tangerine peel is pungent and warm, regulating qi and strengthening the spleen, preventing cold medicines from damaging the spleen and stomach's vital energy; hawthorn is sour, sweet, and slightly warm, promoting digestion and eliminating food stagnation, removing the source of damp heat generated from food. The combined use of these two herbs balances their warming and cooling properties, regulating qi flow, ensuring that the entire formula is nourishing without causing stagnation and clearing without causing harm. This reflects the formulation strategy of simultaneously nourishing and clearing, and regulating both warming and cooling properties, thus improving the overall efficiency of the formula's transformation and transformation.

[0013] Preferably, in this invention, Rehmannia glutinosa and Paeonia suffruticosa are used as principal herbs; Lithospermum erythrorhizon, Paeonia lactiflora, Lonicera japonica and Hedyotis diffusa are used as assistant herbs; Smilax glabra, Artemisia capillaris, Sophora japonica, Typha orientalis and Indigo naturalis are used as adjuvant herbs; and Citrus reticulata and Crataegus pinnatifida are used as guiding herbs.

[0014] Preferably, the raw materials are in the following weight parts: 10 to 30 parts by weight of Rehmannia glutinosa (e.g., 15, 20, or 25 parts by weight); 5 to 20 parts by weight of Paeonia suffruticosa (e.g., 10 or 15 parts by weight); 5 to 20 parts by weight of Lithospermum erythrorhizon (e.g., 10 or 15 parts by weight); 5 to 30 parts by weight of Paeonia lactiflora (e.g., 10, 15, 20, or 25 parts by weight); 10 to 30 parts by weight of Lonicera japonica (e.g., 15, 20, or 25 parts by weight); 20 to 60 parts by weight of Hedyotis diffusa (e.g., 30, 40, or 50 parts by weight); and 10 parts by weight of Smilax glabra. The ingredients are: 10 to 30 parts by weight (e.g., 20, 30 or 40 parts by weight), 15, 20 or 25 parts by weight of Artemisia capillaris, 5 to 30 parts by weight of raw Sophora japonica flowers (e.g., 10, 15, 20 or 25 parts by weight), 5 to 20 parts by weight of raw Typha pollen (e.g., 10 or 15 parts by weight), 4 to 12 parts by weight of Indigo naturalis (6, 8 or 10 parts by weight); 5 to 30 parts by weight of dried tangerine peel (e.g., 10, 15, 20 or 25 parts by weight), and 5 to 30 parts by weight of hawthorn (e.g., 10, 15, 20 or 25 parts by weight).

[0015] Preferably, the weight parts of each raw material are as follows: 15 parts Rehmannia glutinosa, 10 parts Paeonia suffruticosa; 10 parts Lithospermum erythrorhizon, 10 parts Paeonia lactiflora, 15 parts Lonicera japonica, 30 parts Hedyotis diffusa; 15 parts Smilax glabra, 15 parts Artemisia capillaris, 10 parts Sophora japonica, 10 parts Typha orientalis, 6 parts Indigo naturalis; 10 parts Citrus reticulata peel, 10 parts Crataegus pinnatifida.

[0016] In this invention, there are no particular restrictions on the dosage form of the traditional Chinese medicine. Therefore, this invention does not have any particular restrictions on pharmaceutically acceptable excipients, which can be selected and used within the capabilities of those skilled in the art.

[0017] In some embodiments, the excipients may be filler diluents, including but not limited to: microcrystalline cellulose, lactose, starch, dextrin and mannitol.

[0018] In some embodiments, the excipients may be diluted flavoring excipients, including but not limited to: yam powder, fox nut powder and kudzu root powder.

[0019] In some embodiments, the excipients may be adhesive excipients, including but not limited to: hydroxypropyl methylcellulose (HPMC), ethyl cellulose (EC), and pregelatinized starch, which are particularly suitable for use in wet granulation or dry granulation.

[0020] In some embodiments, the excipients may be disintegrating excipients, including but not limited to: sodium carboxymethyl starch, crospovidone, and low-substituted hydroxypropyl cellulose.

[0021] In some embodiments, the excipients may be coating, taste-masking, and sustained-release excipients, including but not limited to: OpadryII, Coloncon, and Surelease (ethyl cellulose aqueous dispersion).

[0022] In some embodiments, the excipients may be solubilizing, emulsifying and permeation-enhancing excipients, including but not limited to: menthol, peppermint oil, cardamom volatile oil, and coix seed oil.

[0023] In some embodiments, the excipients may be surfactants, including but not limited to: Tween 80, poloxamer 188, and lecithin.

[0024] In some embodiments, the excipient may be a modified cyclodextrin, such as hydroxypropyl-β-cyclodextrin (HP-β-CD).

[0025] In some embodiments, the excipient may be a gel matrix carrier excipient, such as natural polysaccharides, including but not limited to: Bletilla striata polysaccharide, ginger polysaccharide and licorice polysaccharide.

[0026] In some embodiments, the excipients may be flavoring, coloring, and aromatic excipients, including but not limited to: inulin, erythritol, gardenia yellow, red yeast rice, lemon oil, and orange oil.

[0027] In some preferred embodiments, the excipients may be special excipients for processing (preferably of the grade of medicinal slices), including but not limited to: (1) rice wine, rice vinegar, and honey, which can guide the medicine to the meridians and reduce toxicity while increasing efficacy; (2) river sand and clam powder, which can be used as heat-conducting media. Therefore, in some more preferred embodiments, the traditional Chinese medicine is a decoction.

[0028] Preferably, the drug is a decoction.

[0029] Preferably, the diabetes mellitus is a type of diabetes mellitus characterized by "damp-heat accumulation and internal obstruction of blood stasis and toxins".

[0030] Preferably, the diabetes-related disease is obesity comorbid with diabetes.

[0031] Preferably, the diabetes-related disease is hyperlipidemia complicated by diabetes.

[0032] Preferably, the application is at least one of the following applications: in the preparation of a medicament for regulating glucose metabolism; in the preparation of a medicament for improving insulin sensitivity; in the preparation of a medicament for protecting the pancreas.

[0033] Preferably, the regulation of glucose metabolism is to lower blood glucose and / or improve glucose tolerance.

[0034] Preferably, the improvement in insulin sensitivity is to reduce insulin resistance or decrease pancreatic β-cell damage.

[0035] Preferably, the pancreas protection involves repairing pancreatic tissue.

[0036] The traditional Chinese medicine composition of the present invention has significant intervention value for diabetes-related diseases, effectively reducing blood glucose levels, improving glucose tolerance and insulin resistance, and has a significant protective effect against diabetes-related liver and pancreatic tissue damage. This expands the application basis in the field of metabolic diseases and provides new theoretical and practical evidence for the treatment of diabetes. Attached Figure Description

[0037] Figure 1 The changes in blood glucose levels in mice were shown. n=8), (compared to the blank control group, * P<0.05, ** P<0.01; compared with the model group, # P<0.05, ## P<0.01).

[0038] Figure 2 The glucose tolerance test and insulin resistance test were displayed. n=8), (compared to the blank control group, * P<0.05, ** P<0.01; compared with the model group, # P<0.05, ## P<0.01).

[0039] Figure 3 The results of mouse serum biochemical assays were shown. n=8)(Compared with the blank control group, * P<0.05, ** P<0.01; compared with the model group, # P<0.05, ## P<0.01).

[0040] Figure 4 The pathological features of the mouse liver are shown (20×).

[0041] Figure 5 The pathological features of the mouse pancreas are shown (10×). Detailed Implementation

[0042] To make the objectives, technical solutions, and advantages of the embodiments of the present invention clearer, the following will clearly and completely describe the technical solutions in the embodiments of the present invention with reference to the accompanying drawings in the embodiments of the present invention. Apparently, the described embodiments are some, but not all, of the embodiments of the present invention. All other embodiments obtained by those of ordinary skill in the art based on the embodiments of the present invention without creative efforts fall within the scope of protection of the present invention.

[0043] Embodiment

[0044] 1 Materials

[0045] 1.1 Experimental Animals

[0046] C57BL / 6J, male, 6 weeks old, purchased from Jiangsu Jicui Yakang Biological Co., Ltd., animal license number: SCXK (Jiangsu) 2023 - 0009, raised in a SPF-class animal room. Animal experiments strictly follow the principles of animal welfare. All animal experiment protocols have been approved by the Experimental Animal Ethics Committee of Beijing Institute of Traditional Chinese Medicine.

[0047] 1.2 Main Reagents and Drugs

[0048] Traditional Chinese medicine composition (10 g of Lithospermum erythrorhizon, 10 g of Paeonia lactiflora, 15 g of Rehmannia glutinosa, 10 g of Moutan cortex, 15 g of Lonicera japonica, 30 g of Hedyotis diffusa, 15 g of Smilax glabra, 10 g of Sophora japonica, 15 g of Artemisia capillaris, 10 g of Pollen typhae, 6 g of Indigo naturalis, 10 g of Citrus reticulata, 10 g of Crataegus pinnatifida), purchased from Beijing Tongrentang Chinese Herbal Pieces Co., Ltd. Calculated according to "Research Methods of Traditional Chinese Medicine Pharmacology" (edited by Chen Qi, People's Medical Publishing House), 21.3 g / kg is the clinical equivalent dose, in the form of a decoction. Decoction method: Weigh 3 doses of medicine totaling 498 g, add 8 times the volume of pure water (498 g / 4000 ml), soak for z min, collect the medicinal liquid after reflux extraction for 40 min, then add 6 times the volume of pure water (498 g / 3000 ml), reflux extract for 20 min, collect the medicinal liquid, combine the two medicinal liquids and concentrate to the use dose, and store in a 4°C refrigerator.

[0049] Streptozotocin (STZ, Sigma - Aldrich, V900890); D - anhydrous glucose (Solarbio, batch number: 24231121001); Insulin (MedChemExpress, HY - P0035); Jinqi Jiangtang Tablets (Drentang Group Co., Ltd., national drug approval number: Z10920027, batch number: 870372); Tribromoethanol (Nanjing Anjieyou Biotechnology Co., Ltd., TG - Avertin - M); High - fat feed (H10060) purchased from Beijing Huafukang Biotechnology Co., Ltd..

[0050] 1.3 Main Instruments

[0051] Toshiba fully automatic biochemical analyzer, Leica ASP300S fully automatic dehydrator, Leica EG1150 paraffin embedding machine, Leica RM2255 fully automatic rotary microtome, Leica Autostainer XL ST5010 fully automatic staining machine, Yuwell 580 blood glucose meter.

[0052] 2 Methods

[0053] 2.1 Animal Models and Group Administration

[0054] After all mice adapted to the environment for 1 week, they were continuously fed with a high-fat diet (growth feed (H10060), license number: SCXK (Beijing) 2024-0003; production unit: Beijing Huafukang Biotechnology Co., Ltd.) for 4 weeks and allowed to eat freely. After fasting for 12 hours, STZ (60 mg / kg / d, prepared with 0.1 M pH 4.5 citrate buffer solution, prepared immediately before use) was intraperitoneally injected continuously for 4 days to induce an increase in blood glucose in mice. Eight mice fed with a conventional diet (feed name: rodent feed; license number: SCXK (Beijing) 2024-0001; production unit: Spf (Beijing) Biotechnology Co., Ltd.) (eating freely) were used as the blank control group and given the same volume of citrate buffer solution. Three days later, mice with a fasting blood glucose level ≥ 11.1 mmol / L were considered successful models and used for subsequent studies.

[0055] The hyperglycemic mice were randomly divided into 3 groups (8 mice in each group): model control group (pure water), traditional Chinese medicine formula group (21.3 g / kg), and Jinqi Jiangtang Tablet group (1.5 g / kg), once a day, intragastrically administered at 10 mL / kg for 4 weeks. The mice in the blank control group were given an equal amount of pure water. Body weight and fasting blood glucose levels were monitored once a week. At the 4th week after administration, a glucose tolerance test and an insulin resistance test were conducted. Finally, after intraperitoneal injection of an anesthetic, blood was collected from the eye socket, the mice were sacrificed by cervical dislocation, and the liver and pancreas were removed for relevant pathological examinations.

[0056] 2.2 Detection Indexes and Methods

[0057] 2.2.1 Detection of Fasting Blood Glucose and Random Blood Glucose in Mice

[0058] The fasting blood glucose of mice was detected at the 1st, 2nd, and 3rd weeks after intragastric administration: fast for 12 hours before the experiment, cut the mouse tail, and detect the fasting blood glucose of mice with a blood glucose meter; the random blood glucose of mice was detected at the 4th week after intragastric administration: do not fast before the experiment, and detect the random blood glucose of mice with a blood glucose meter.

[0059] 2.2.2 Oral Glucose Tolerance Test (OGTT) in Mice

[0060] Mice were fasted for 12 hours before the experiment. Their body weight was recorded, and a glucose solution of 100 mg / mL was prepared using physiological saline at a concentration of 1 g / kg (glucose / body weight). The solution was administered by gavage at a rate of 10 mL / kg. Blood glucose levels were measured at 0, 30, 60, and 120 minutes for each mouse.

[0061] 2.2.3 Insulin Tolerance Test (ITT) in Mice

[0062] Mice were fasted for 4 hours before the experiment. Their body weight was recorded, and an insulin solution was prepared with physiological saline at a concentration of 0.75 IU / kg (insulin / body weight) and administered by gavage at a rate of 10 mL / kg. Blood glucose levels were measured for each mouse at 0, 30, 60, and 120 minutes.

[0063] 2.2.4 Serum biochemical detection

[0064] After the experiment, the eyes of anesthetized mice were removed and blood was collected. Serum was collected after centrifugation at 3000 rpm for 15 minutes. A fully automated biochemical analyzer was used to detect serum glucose, fructosamine, four lipid parameters (total cholesterol, triglycerides, low-density lipoprotein, and high-density lipoprotein), liver function (alanine aminotransferase and aspartate aminotransferase), and kidney function (creatinine and urea).

[0065] 2.2.5 Histopathological changes in mice

[0066] Hematoxylin and eosin (HE) staining was used to observe the pathological changes in the liver and pancreas of mice. Mice were euthanized by cervical dislocation, and the liver and pancreas (including the spleen for localization) were harvested, fixed in 10% formaldehyde, and routinely dehydrated, embedded, sectioned, and stained. Three stained sections from each specimen were selected for histopathological observation and photographed.

[0067] 2.3 Statistical Methods

[0068] Statistical analysis of experimental data is expressed as mean ± standard deviation. The data were analyzed using SPSS 26.0 software. Homogeneity of variance was determined using one-way ANOVA, and unequal variances were analyzed using non-parametric tests. P < 0.05 was considered statistically significant.

[0069] 3 Results

[0070] 3.1 Effects of Traditional Chinese Medicine Composition on Blood Glucose in Mice

[0071] Compared with the blank control group, the blood glucose levels of mice in the model control group were continuously rising; the traditional Chinese medicine composition could reduce the elevated blood glucose, showing a significant statistical effect as early as the first week of administration, and this effect was even more significant by the third week (P<0.01). Figure 1 A). At week 4 after administration, the random blood glucose level in the traditional Chinese medicine composition group was significantly lower than that in the model control group, which was statistically significant. Figure 1 B).

[0072] After oral administration of glucose (1 g / kg), the blood glucose levels in the model control group mice were significantly higher than those in the blank group, indicating impaired glucose tolerance. Although the area under the curve (AUC) of the herbal composition was not statistically different from that in the model group (3455±153.3 vs. 3765±64.35) (Table 2), the AUC value of the herbal composition group was lower than that of the model group, suggesting its potential to improve glucose tolerance. At 120 minutes, the blood glucose level in the herbal composition group was significantly lower (27.4±0.87 vs. 32.6±1.21) (P<0.01), indicating that the effect of the herbal composition is mainly reflected in improving the recovery of glucose tolerance in the later stage or accelerating postprandial glucose clearance. Its mechanism may be related to delaying glucose absorption or promoting hepatic glycogen uptake in the later stage. Figure 2 A). After insulin injection (0.75 U / kg), insulin sensitivity was significantly reduced in the model control group mice, while the traditional Chinese medicine compound group showed improvement at key time points after insulin injection: blood glucose dropped to (21.22±3.5 mmol / L) at 30 minutes, significantly lower than that in the model group (26.4±4.11 mmol / L) (P<0.05); and further decreased to (8.79±0.75 mmol / L) at 60 minutes, significantly lower than that in the model group (10.2±0.87 mmol / L) (P<0.05), suggesting that it can significantly enhance insulin-stimulated glucose uptake in peripheral tissues (muscle / fat). Figure 2 B).

[0073] Table 2. Area under the blood glucose curve for glucose tolerance test and insulin resistance test.

[0074]

[0075] 3.2 Effects of Traditional Chinese Medicine Combinations on Serum Biochemistry in Mouse Models

[0076] from Figure 3The results showed that, compared with the blank control group, the serum glucose, fructosamine, total cholesterol, triglycerides, low-density lipoprotein, alanine aminotransferase, and aspartate aminotransferase levels in the model control group mice were significantly increased, while urea levels were significantly decreased. Compared with the model control group, the traditional Chinese medicine composition significantly reduced serum glucose and fructosamine levels. Fructosamine is a product of the non-enzymatic glycation reaction between serum proteins (mainly albumin) and glucose, reflecting the average blood glucose level over the past 1-3 weeks, indicating a stable inhibitory effect on blood glucose. The traditional Chinese medicine composition significantly reduced serum triglyceride (TG) levels and increased high-density lipoprotein cholesterol (HDL-C) levels in mice, suggesting a good lipid-regulating effect. This effect helps improve diabetes-related lipid metabolism disorders, reduce insulin resistance, and lower the risk of complications such as fatty liver and atherosclerosis. The traditional Chinese medicine composition did not show significant changes in serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), urea, and creatinine levels in mice, indicating that the composition did not have a significant impact on liver or kidney function during in vivo administration. The results support the conclusion that the traditional Chinese medicine composition of the present invention has good hepato-renal safety and does not significantly damage liver and kidney function in the short term, proving that the drug has low hepato-renal toxicity, is suitable for long-term use, and can be used for the treatment of metabolic diseases.

[0077] 3.3 Effects of Traditional Chinese Medicine Composition on the Histopathological Characteristics of Mouse Liver and Pancreas

[0078] Microscopic observation showed that in the blank control group, the liver tissue was centered on the central vein, with hepatocyte cords arranged radially, and the sinusoids (blood sinuses) were of uniform width, without fibrous septa or pseudolobule formation. In the model control group, the hepatocytes were irregularly arranged, with numerous vacuolar degenerations, accompanied by inflammatory cell infiltration and fibrosis. In the herbal composition group, the hepatocytes were arranged more neatly than in the model group, with a more complete structure, significantly reduced vacuolar degenerations, and significantly reduced inflammatory cell infiltration. Figure 4 The above results indicate that the traditional Chinese medicine composition can significantly improve liver tissue structure and reduce hepatocyte damage and inflammatory response.

[0079] In the blank control group, the pancreatic histological structure was intact, with round or oval islets with clear boundaries and well-defined β cells (abundant cytoplasm, large, centrally located nuclei) clearly demarcated from exocrine glands. In the model control group, the islets were significantly smaller, with blurred boundaries, losing their normal round or oval structure. The islet cell density was reduced, and the cells were loosely arranged, with some areas replaced by fibrous tissue. Lymphocyte infiltration was observed within and around the islets. In the herbal composition group, the islet structure was more regular, larger than that in the model group, with clear boundaries, and the islet β cells were tightly arranged with abundant cytoplasm. Figure 5 The above results indicate that the traditional Chinese medicine composition can improve pancreatic structure, enhance the integrity of islets, and reduce islet cell damage and inflammatory response.

[0080] In summary, the traditional Chinese medicine composition of this invention significantly regulates blood glucose and lipid metabolism, improves insulin sensitivity, and effectively protects the liver and pancreas through multi-target action. Experimental results show that this composition can lower blood glucose, improve glucose tolerance, regulate triglyceride and high-density lipoprotein levels, alleviate insulin resistance, and exhibit significant repair effects in liver and pancreatic tissues. Furthermore, the traditional Chinese medicine composition does not cause significant damage to liver and kidney function in the short term, demonstrating good safety. Therefore, the traditional Chinese medicine composition of this invention has broad application prospects in the treatment of diabetes and related metabolic diseases.

[0081] Finally, it should be noted that the above embodiments are only used to illustrate the technical solutions of the present invention, and not to limit them; although the present invention has been described in detail with reference to the foregoing embodiments, those skilled in the art should understand that modifications can still be made to the technical solutions described in the foregoing embodiments, or equivalent substitutions can be made to some of the technical features; and these modifications or substitutions do not cause the essence of the corresponding technical solutions to deviate from the spirit and scope of the technical solutions of the embodiments of the present invention.

Claims

1. The use of a traditional Chinese medicine composition in the preparation of a medicament for treating diabetes or diabetes-related diseases, wherein the traditional Chinese medicine composition is made from the following raw materials and optional pharmaceutically acceptable excipients: Rehmannia glutinosa, Paeonia suffruticosa, Lithospermum erythrorhizon, Paeonia lactiflora, Lonicera japonica, Hedyotis diffusa, Smilax glabra, Artemisia capillaris, Sophora japonica, Typha orientalis, Indigo naturalis, Citrus reticulata peel, and Crataegus pinnatifida.

2. The application according to claim 1, characterized in that, In the aforementioned raw materials, Rehmannia glutinosa and Paeonia suffruticosa are the principal herbs; Lithospermum erythrorhizon, Paeonia lactiflora, Lonicera japonica, and Hedyotis diffusa are the assistant herbs; Smilax glabra, Artemisia capillaris, Sophora japonica, Typha orientalis, and Indigo naturalis are the adjuvant herbs; and Citrus reticulata and Crataegus pinnatifida are the guiding herbs.

3. The application according to claim 1, characterized in that, The weight proportions of each active pharmaceutical ingredient are as follows: 10 to 30 parts by weight of Rehmannia glutinosa and 5 to 20 parts by weight of Paeonia suffruticosa. 5 to 20 parts by weight of Lithospermum erythrorhizon, 5 to 30 parts by weight of Paeonia lactiflora, 10 to 30 parts by weight of Lonicera japonica, and 20 to 60 parts by weight of Hedyotis diffusa. Smilax glabra 10 to 50 parts by weight, Artemisia capillaris 10 to 30 parts by weight, Sophora japonica 5 to 30 parts by weight, Typha orientalis 5 to 20 parts by weight, Indigo naturalis 4 to 12 parts by weight. 5 to 30 parts by weight of dried tangerine peel and 5 to 30 parts by weight of hawthorn.

4. The application according to claim 3, characterized in that, The weight proportions of each active pharmaceutical ingredient are as follows: 15 parts by weight of Rehmannia glutinosa and 10 parts by weight of Paeonia suffruticosa. 10 parts by weight of Lithospermum erythrorhizon, 10 parts by weight of Paeonia lactiflora, 15 parts by weight of Lonicera japonica, and 30 parts by weight of Hedyotis diffusa. Smilax glabra 15 parts by weight, Artemisia capillaris 15 parts by weight, Sophora japonica 10 parts by weight, Typha orientalis 10 parts by weight, Indigo naturalis 6 parts by weight. 10 parts by weight of dried tangerine peel and 10 parts by weight of hawthorn.

5. The application according to claim 1, characterized in that, The drug is a decoction.

6. The application according to claim 1, characterized in that, The diabetes described is a type of diabetes characterized by "damp-heat accumulation and internal obstruction of blood stasis and toxins".

7. The application according to claim 1, characterized in that, The diabetes-related disease mentioned refers to obesity that is a complication of diabetes.

8. The application according to claim 1, characterized in that, The diabetes-related disease mentioned refers to hyperlipidemia that is a complication of diabetes.

9. The application according to claim 1, characterized in that, The drug is used for at least one of the following purposes: regulating blood glucose metabolism; improving insulin sensitivity; and protecting the pancreas.

10. The application according to claim 9, characterized in that: The regulation of glucose metabolism is to lower blood glucose and / or improve glucose tolerance; The improvement in insulin sensitivity refers to reducing insulin resistance or decreasing pancreatic β-cell damage. The protection of the pancreas refers to the repair of pancreatic tissue.

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