Tanglotide series composition with functions of improving pancreatic beta cell function, regulating blood fat, repairing liver and kidney injury, resisting inflammation and resisting oxidation and application of Tanglotide series composition with functions of improving pancreatic beta cell function, regulating blood fat and repairing liver and kidney injury

Abstract

The invention discloses a tanlotide series composition with functions of improving pancreatic beta cell functions, regulating blood fat, repairing liver and kidney injury, resisting inflammation and resisting oxidation and application thereof, and belongs to the technical field of medicines. The composition is prepared from radix trichosanthis, radix puerariae, radix ophiopogonis, radix codonopsis, poria cocos, fructus mume, radix astragali seu hedysari preparata, radix glycyrrhizae, fructus schisandrae chinensis, radix rehmanniae, folium eriobotryae powder, epigallocatechin gallate, instant bean flour, corn oligopeptide powder, wheat oligopeptide powder and soybean peptide powder, and meanwhile, the composition further comprises synergistic components. The synergistic component is one or more of a ginseng extract, PQQ, a turmeric extract and black pepper powder, and the composition has the effect of improving the functions of pancreatic beta cells and can effectively reduce the insulin resistance index. The traditional Chinese medicine composition also has a remarkable effect of regulating blood fat, and meanwhile, can repair liver and kidney injuries caused by complications such as hyperglycemia and hyperlipidemia. In addition, it is found that the composition has good anti-inflammatory and anti-oxidation effects, inflammation caused by in-vivo tissue lesions can be effectively resisted, meanwhile, the content of glutathione peroxidase and superoxide dismutase in the body is increased, and tissue cell recovery is accelerated through the combined action of the glutathione peroxidase and the superoxide dismutase.

Description

Technical Field

[0001] This invention belongs to the field of pharmaceutical technology, specifically relating to a series of Tangluotai compositions and their applications that improve pancreatic β-cell function, regulate blood lipids, repair liver and kidney damage, and have anti-inflammatory and antioxidant effects. Background Technology

[0002] With societal development and the expansion of e-commerce, people have become accustomed to convenient lifestyles, leading to reduced travel and a gradual decline in bodily functions. Simultaneously, prolonged bed rest and sitting, increased work stress, and irregular sleep patterns can all cause damage and dysfunction of pancreatic β-cells. Pancreatic β-cells, located in the central part of the islets of Langerhans, account for approximately 60%-80% of the total islet cells and are the core cells of the pancreatic endocrine system. The core function of pancreatic β-cells is to secrete insulin, and the liver and kidneys are key target organs for insulin's metabolic regulation. Blood lipids (lipid metabolism) are directly regulated by insulin. Conversely, abnormal liver and kidney function or dyslipidemia can directly damage pancreatic β-cell function through metabolic feedback, forming a two-way "regulation-feedback" relationship. When pancreatic β-cell function declines and insulin secretion is insufficient, the above regulation fails, directly leading to dyslipidemia: elevated T-scores, decreased HDL-C, and increased small dense LDL-C, which are typical hyperlipidemia manifestations of "metabolic syndrome." Abnormalities in the liver (such as fatty liver), kidneys (such as nephropathy), and blood lipids (such as high T content) can in turn damage pancreatic β cells, forming a vicious cycle of "decreased function → organ damage → further decline in function".

[0003] Market research indicates that 85% of obese patients with type 2 diabetes take metformin, a medication that can easily cause liver and kidney damage, potentially leading to irreversible liver and kidney disease. Liver and kidney damage can also be caused by other factors, including viral infections, drug or toxin damage, autoimmune diseases, genetic disorders, and alcohol abuse. The severity of the damage can range from mild functional abnormalities to severe organ failure.

[0004] Studies have shown that persistently high blood lipid levels, commonly known as hyperlipidemia, are a more likely cause of liver and kidney damage. Currently, the prevalence of dyslipidemia among adults in my country is over 40%, with an estimated 560 million people suffering from this condition nationwide. Hyperlipidemia is a metabolic disease. Excessive intake of foods high in fat, especially those high in saturated fatty acids such as fatty meat, animal organs, and seafood, as well as an increase in dietary lipids, can all lead to elevated blood lipids. Unhealthy lifestyle habits such as smoking and excessive alcohol consumption are also contributing factors. Hyperlipidemia is a common and frequently occurring disease, and a major cause of cardiovascular and cerebrovascular diseases. Untreated hyperlipidemia can lead to severe conditions such as angina, sudden myocardial infarction, and cerebral arteriosclerosis, which can subsequently induce cerebral infarction, resulting in stroke, hemiplegia, aphasia, and even death.

[0005] Inflammation, commonly known as "getting inflamed," is a basic pathological process primarily driven by a defensive response in biological tissues in response to stimuli such as trauma or infection. Sometimes, inflammation can trigger an allergic reaction in the body's own immune system, leading to the attack of the body's own tissues and cells. If the inflammatory focus experiences cell degeneration, necrosis, or abnormal metabolic function, or if there is mechanical obstruction or compression caused by inflammatory exudates, or conditions such as diabetes or hyperlipidemia, it can lead to vascular endothelial damage and trigger an inflammatory response, potentially causing functional impairment of the inflamed organ in severe cases.

[0006] As we age, the production of free radicals in the body gradually increases, leading to cell damage and aging. The human body contains a large amount of reactive oxygen species (ROS). Excessive ROS can cause aging and various functional disorders through oxidation reactions, and further, may lead to diseases such as cancer. Antioxidants can neutralize free radicals, slow down the aging process of cells, keep skin youthful, and reduce the risk of age-related diseases. Oxidative stress is one of the important factors leading to cardiovascular disease. Antioxidants can help lower blood lipids and blood pressure, reduce vascular inflammation, and lower the risk of cardiovascular disease. At the same time, antioxidants can also improve blood circulation and prevent thrombosis.

[0007] Currently, in clinical medicine, most patients with type 2 diabetes take metformin to lower their blood sugar. Metformin primarily acts on the liver, inhibiting gluconeogenesis and glycogenolysis, thereby reducing the release of glucose into the bloodstream. It also affects intestinal function, reducing glucose absorption and thus decreasing the amount of glucose entering the bloodstream, achieving a blood sugar-lowering effect. However, this method only addresses the external symptoms of high blood sugar and cannot fundamentally resolve the underlying condition. Furthermore, long-term use of this medication can damage the liver and intestinal function.

[0008] The number of patients with hyperlipidemia is increasing year by year due to changes in lifestyle and increased work pressure, and the age distribution is becoming younger. Statins and fibrates are commonly used clinically to reduce cholesterol synthesis and enhance lipoprotein lipase activity by inhibiting HMI-CoA reductase, the rate-limiting enzyme in cholesterol synthesis. Long-term use can lead to elevated transaminase levels, resulting in abnormal liver function, and can also cause side effects such as nausea, vomiting, abdominal distension, dizziness, headache, rash, itching, cognitive impairment, and memory loss. Summary of the Invention

[0009] In order to solve the above-mentioned technical problems, the present invention provides a series of Tangluotai compositions and their applications that have the functions of improving pancreatic β-cell function, regulating blood lipids, repairing liver and kidney damage, anti-inflammatory and antioxidant properties.

[0010] The present invention provides a method that enhances pancreatic β-cell function, regulates blood lipids, repairs liver and kidney damage, and has anti-inflammatory and antioxidant effects.

[0011] The Tangluotai series composition comprises, by weight, 150-900 parts of Trichosanthes kirilowii root, 150-900 parts of Pueraria lobata root, 100-600 parts of Ophiopogon japonicus root, 200-1200 parts of Codonopsis pilosula root, 100-600 parts of Poria cocos root, 100-600 parts of Prunus mume fruit, 50-300 parts of Astragalus membranaceus root, 50-300 parts of processed Astragalus membranaceus root, 100-600 parts of Glycyrrhiza uralensis root, and 100-600 parts of Schisandra chinensis fruit. The formula consists of 100-600 parts of Rehmannia glutinosa, 2-50 parts of Eriobotrya japonica leaf powder, 5-140 parts of epigallocatechin gallate, 30-2000 parts of instant soy powder, 0.5-20 parts of corn oligopeptide powder, 0.5-20 parts of wheat oligopeptide powder, 0.5-20 parts of soybean peptide powder, and synergistic ingredients; the synergistic ingredients are composed of one or more of the following: 5-120 parts of ginseng extract, 20-500 parts of turmeric extract, 0.4-10 parts of PQQ, and 0.1-5.0 parts of black pepper powder.

[0012] Further, the composition comprises, by weight, 225-675 parts of Trichosanthes kirilowii root, 225-675 parts of Pueraria lobata root, 200-450 parts of Ophiopogon japonicus root, 400-900 parts of Codonopsis pilosula root, 200-450 parts of Poria cocos root, 200-450 parts of Prunus mume fruit, 100-225 parts of Astragalus membranaceus root, 100-225 parts of processed Astragalus membranaceus root, 200-450 parts of Glycyrrhiza uralensis root, 200-450 parts of Schisandra chinensis fruit, and Rehmannia glutinosa root. It consists of 200-450 parts of loquat leaf powder, 5-20 parts of epigallocatechin gallate, 15-55 parts of instant soy powder, 80-1000 parts of corn oligopeptide powder, 0.5-10 parts of wheat oligopeptide powder, 0.5-10 parts of soybean peptide powder, and synergistic ingredients; the synergistic ingredients are composed of one or more of the following: 12-50 parts of ginseng extract, 50-200 parts of turmeric extract, 1.0-4.0 parts of PQQ, and 0.1-1.0 parts of black pepper powder.

[0013] Further, the composition, by weight, comprises 375-540 parts of Trichosanthes kirilowii root, 375-540 parts of Pueraria lobata root, 250-360 parts of Ophiopogon japonicus root, 500-720 parts of Codonopsis pilosula root, 250-360 parts of Poria cocos root, 250-360 parts of Prunus mume fruit, 125-180 parts of Astragalus membranaceus root, 125-180 parts of processed Astragalus membranaceus root, 250-360 parts of Glycyrrhiza uralensis root, 250-360 parts of Schisandra chinensis fruit, 250-360 parts of Rehmannia glutinosa root, 7-15 parts of Eriobotrya japonica leaf powder, 18-42 parts of epigallocatechin gallate, 100-500 parts of instant soy flour, 1-5 parts of corn oligopeptide powder, 1-5 parts of wheat oligopeptide powder, 1-5 parts of soybean peptide powder, and a synergistic ingredient; the synergistic ingredient comprises 15-35 parts of ginseng extract, 65-150 parts of turmeric extract, and PQQ. One or more of the following: 1.5-2.5 parts and 0.2-0.5 parts black pepper powder.

[0014] Further, the composition comprises, by weight, 450 parts of Trichosanthes kirilowii root, 450 parts of Pueraria lobata root, 300 parts of Ophiopogon japonicus root, 600 parts of Codonopsis pilosula root, 300 parts of Poria cocos root, 300 parts of Prunus mume fruit, 150 parts of Astragalus membranaceus root, 150 parts of processed Astragalus membranaceus root, 300 parts of Glycyrrhiza uralensis root, 300 parts of Schisandra chinensis fruit, 300 parts of Rehmannia glutinosa root, 10 parts of Eriobotrya japonica leaf powder, 28 parts of epigallocatechin gallate, 120 parts of instant soy flour, 1 part of corn oligopeptide powder, 1 part of wheat oligopeptide powder, 1 part of soybean peptide powder, and a synergistic ingredient; the synergistic ingredient is composed of one or more of the following: 24 parts of ginseng extract, 100 parts of turmeric extract, 2 parts of PQQ, and 0.2 parts of black pepper powder.

[0015] The method for preparing the Tangluotai series compositions of the present invention, which have the functions of improving pancreatic β-cell function, regulating blood lipids, repairing liver and kidney damage, anti-inflammatory and antioxidant effects, is as follows:

[0016] (1) Weigh out the following ingredients according to weight: 150-900 parts of Trichosanthes kirilowii root, 150-900 parts of Pueraria lobata root, 100-600 parts of Ophiopogon japonicus root, 200-1200 parts of Codonopsis pilosula root, 100-600 parts of Poria cocos root, 100-600 parts of Prunus mume fruit, 50-300 parts of Astragalus membranaceus root, 50-300 parts of processed Astragalus membranaceus root, 100-600 parts of Glycyrrhiza uralensis root, 100-600 parts of Schisandra chinensis fruit, and 100-600 parts of Rehmannia glutinosa root. The mixture comprises 600 parts of loquat leaf powder, 2-50 parts of epigallocatechin gallate, 5-140 parts of instant soy powder, 30-2000 parts of corn oligopeptide powder, 0.5-20 parts of wheat oligopeptide powder, 0.5-20 parts of soybean peptide powder, and a synergistic ingredient; the synergistic ingredient is composed of one or more of the following: 5-120 parts of ginseng extract, 20-500 parts of turmeric extract, 0.4-10 parts of PQQ, and 0.1-5.0 parts of black pepper powder; for later use.

[0017] (2) The weighed Trichosanthes kirilowii, Pueraria lobata, Ophiopogon japonicus, Codonopsis pilosula, Poria cocos, Prunus mume, Astragalus membranaceus, processed Astragalus membranaceus, Glycyrrhiza uralensis, Schisandra chinensis and Rehmannia glutinosa were extracted and concentrated to obtain an extract. The extract was diluted with water and stirred evenly to obtain an extract solution.

[0018] (3) Loquat leaf powder, epigallocatechin gallate, instant soybean powder, corn oligopeptide powder, wheat oligopeptide powder and soybean peptide powder are added to the extract, mixed evenly and filtered to obtain a mixture.

[0019] (4) Add one or more of ginseng extract, turmeric extract, PPQ and black pepper powder to the above mixture, mix evenly and filter to obtain the composition.

[0020] Furthermore, the composition also includes any pharmaceutically acceptable excipients.

[0021] Furthermore, the composition can be prepared into dosage forms including oral solutions, tablets, granules, capsules, injections, pills, oral liquids, and creams.

[0022] The present invention relates to the application of a Tangluotai series composition that improves pancreatic β-cell function, regulates blood lipids, repairs liver and kidney damage, and has anti-inflammatory and antioxidant properties. The composition is used as a drug to regulate insulin resistance index, alleviate symptoms and complications caused by a decrease in the number of pancreatic β-cells, reduce fat levels in patients with hyperlipidemia, alleviate hyperlipidemia and its complications, repair liver, kidney and pancreatic damage caused during the treatment of hyperglycemia and hyperlipidemia, and / or alleviate complications caused by type 2 diabetes and hyperlipidemia.

[0023] The reduction of fat levels in patients with hyperlipidemia refers to reducing total cholesterol, triglycerides, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and free fatty acid levels.

[0024] The pharmaceutical composition of the present invention has the ability to repair liver, kidney and pancreas damage caused during the treatment of hyperglycemia and hyperlipidemia, and can also alleviate a variety of complications caused by type 2 diabetes and hyperlipidemia, and improve the quality of life of patients with type 2 diabetes and hyperlipidemia.

[0025] Furthermore, the regulation of the insulin resistance index is achieved by increasing the number of pancreatic β cells in patients with hyperglycemia.

[0026] Furthermore, the aforementioned relief of indigestion and steatorrhea, weight loss, ketoacidosis and its complications caused by a decrease in the number of pancreatic β cells.

[0027] The present invention has the following beneficial effects:

[0028] This invention discloses a Tangluotai series composition that enhances pancreatic β-cell function, regulates blood lipids, repairs liver and kidney damage, and possesses anti-inflammatory and antioxidant properties. The composition comprises Trichosanthes kirilowii root, Pueraria lobata root, Ophiopogon japonicus root, Codonopsis pilosula root, Poria cocos root, Prunus mume fruit, Astragalus membranaceus root, processed Astragalus membranaceus root, Glycyrrhiza uralensis root, Schisandra chinensis fruit, Rehmannia glutinosa root, Eriobotrya japonica leaf powder, epigallocatechin gallate, instant soy powder, corn oligopeptide powder, wheat oligopeptide powder, and soybean peptide powder. The composition also contains synergistic components, one or more of ginseng extract, PQQ, turmeric extract, and black pepper powder. This composition enhances pancreatic β-cell function and effectively reduces the insulin resistance index. It also has a significant effect on regulating blood lipids and repairs liver and kidney damage caused by complications such as hyperglycemia and hyperlipidemia. Furthermore, the composition exhibits excellent anti-inflammatory and antioxidant effects, effectively combating inflammation caused by tissue lesions and increasing the levels of glutathione peroxidase and superoxide dismutase in the body, working together to accelerate tissue cell recovery. Detailed Implementation

[0029] To make the objectives, technical solutions, and advantages of the embodiments of the present invention clearer, the spirit of the contents disclosed in the present invention will be described in detail below. After understanding the embodiments of the present invention, any person skilled in the art can make changes and modifications based on the technology taught in the present invention without departing from the spirit and scope of the present invention.

[0030] The illustrative embodiments and descriptions of the present invention are used to explain the present invention, but are not intended to limit the present invention.

[0031] The specific experimental research content in the embodiments of the composition of the present invention is as follows:

[0032] 1. Experimental Materials

[0033] 1.1 Laboratory Animals

[0034] SPF-grade male SD rats, weighing 200±20g, 7-8 weeks old, were purchased from Beijing Vital River Laboratory Animal Technology Co., Ltd. The animals were housed in an SPF-grade laboratory (temperature 20~26℃, relative humidity 40%~70%) for 5 days for acclimatization, with free access to water and food.

[0035] 1.2 Experimental reagents

[0036] 1.2.1 Test Sample

[0037] The overall formulation of the composition in this invention is as follows: 450g of Trichosanthes kirilowii root, 450g of Pueraria lobata root, 300g of Ophiopogon japonicus root, 600g of Codonopsis pilosula root, 300g of Poria cocos root, 300g of Prunus mume fruit, 150g of Astragalus membranaceus root, 150g of processed Astragalus membranaceus root, 300g of Glycyrrhiza uralensis root, 300g of Schisandra chinensis fruit, 300g of Rehmannia glutinosa root, 10g of Eriobotrya japonica leaf powder, 28g of epigallocatechin gallate, 120g of instant soybean powder, 1g of corn oligopeptide powder, 1g of wheat oligopeptide powder, and 1g of soybean peptide powder. The composition also contains synergistic components, namely one or more of the following: 24g of ginseng extract, 2g of PQQ, 100g of turmeric extract, and 0.2g of black pepper powder.

[0038] Compositions 1-12 are prepared by combining the above-mentioned components in the specified amounts.

[0039] Composition 1: Take 450g of Trichosanthes kirilowii root, 450g of Pueraria lobata root, 300g of Ophiopogon japonicus root, 600g of Codonopsis pilosula root, 300g of Poria cocos root, 300g of Prunus mume fruit, 150g of Astragalus membranaceus root, 150g of processed Astragalus membranaceus root, 300g of Glycyrrhiza uralensis root, 300g of Schisandra chinensis fruit, and 300g of Rehmannia glutinosa root. Extract and concentrate to obtain an extract. Add water to the extract and make up to 4000ml. Stir evenly to obtain Composition 1.

[0040] Composition 2: Take 24g of ginseng extract, 2g of PQQ, 100g of turmeric extract and 0.2g of black pepper powder, add water to make up to 4000ml, mix and prepare composition 2.

[0041] Composition 3: Take 10g of loquat leaf powder, 28g of epigallocatechin gallate, 120g of instant soy powder, 1g of corn oligopeptide powder, 1g of wheat oligopeptide powder, and 1g of soybean peptide powder, add water to make up to 4000ml, mix evenly and then prepare composition 3.

[0042] Composition 4: Take 10g of loquat leaf powder, 28g of epigallocatechin gallate, 120g of instant soy powder, 1g of corn oligopeptide powder, 1g of wheat oligopeptide powder, 1g of soybean peptide powder, 24g of ginseng extract, 2g of PQQ, 100g of turmeric extract and 0.2g of black pepper powder, add water to make up to 4000ml, mix evenly to obtain composition 4.

[0043] Composition 5: Take 450g of Trichosanthes kirilowii root, 450g of Pueraria lobata root, 300g of Ophiopogon japonicus root, 600g of Codonopsis pilosula root, 300g of Poria cocos root, 300g of Prunus mume fruit, 150g of Astragalus membranaceus root, 150g of processed Astragalus membranaceus root, 300g of Glycyrrhiza uralensis root, 300g of Schisandra chinensis fruit, and 300g of Rehmannia glutinosa root. Extract and concentrate to obtain an extract. Add water to the extract and make up to 4000ml to obtain an extract. Add 10g of Eriobotrya japonica leaf powder, 28g of epigallocatechin gallate, 120g of instant soybean powder, 1g of corn oligopeptide powder, 1g of wheat oligopeptide powder, and 1g of soybean peptide powder to the extract. Mix evenly and filter to obtain composition 5.

[0044] Composition 6: Take 450g of Trichosanthes kirilowii root, 450g of Pueraria lobata root, 300g of Ophiopogon japonicus root, 600g of Codonopsis pilosula root, 300g of Poria cocos root, 300g of Prunus mume fruit, 150g of Astragalus membranaceus root, 150g of processed Astragalus membranaceus root, 300g of Glycyrrhiza uralensis root, 300g of Schisandra chinensis fruit, and 300g of Rehmannia glutinosa root. Extract and concentrate to obtain an extract. Add water to the extract and make up to 4000ml to obtain an extract. Add 10g of Eriobotrya japonica leaf powder, 28g of epigallocatechin gallate, 120g of instant soybean powder, 1g of corn oligopeptide powder, 1g of wheat oligopeptide powder, 1g of soybean peptide powder, and 2g of PQQ to the extract. Mix evenly and filter to obtain composition 6.

[0045] Composition 7: Take 450g of Trichosanthes kirilowii root, 450g of Pueraria lobata root, 300g of Ophiopogon japonicus root, 600g of Codonopsis pilosula root, 300g of Poria cocos root, 300g of Prunus mume fruit, 150g of Astragalus membranaceus root, 150g of processed Astragalus membranaceus root, 300g of Glycyrrhiza uralensis root, 300g of Schisandra chinensis fruit, and 300g of Rehmannia glutinosa root. Extract and concentrate to obtain an extract. Add water to the extract and make up to 4000ml to obtain an extract. Add 10g of Eriobotrya japonica leaf powder, 28g of epigallocatechin gallate, 120g of instant soybean powder, 1g of corn oligopeptide powder, 1g of wheat oligopeptide powder, 1g of soybean peptide powder, 100g of turmeric extract, and 0.2g of black pepper powder to the extract. Mix well and filter to obtain composition 7.

[0046] Composition 8: Take 450g of Trichosanthes kirilowii root, 450g of Pueraria lobata root, 300g of Ophiopogon japonicus root, 600g of Codonopsis pilosula root, 300g of Poria cocos root, 300g of Prunus mume fruit, 150g of Astragalus membranaceus root, 150g of processed Astragalus membranaceus root, 300g of Glycyrrhiza uralensis root, 300g of Schisandra chinensis fruit, and 300g of Rehmannia glutinosa root. Extract and concentrate to obtain an extract. Add water to the extract and make up to 4000ml to obtain an extract. Add 10g of Eriobotrya japonica leaf powder, 28g of epigallocatechin gallate, 120g of instant soybean powder, 1g of corn oligopeptide powder, 1g of wheat oligopeptide powder, 1g of soybean peptide powder, and 24g of ginseng extract to the extract. Mix evenly and filter to obtain composition 8.

[0047] Composition 9: Take 450g of Trichosanthes kirilowii root, 450g of Pueraria lobata root, 300g of Ophiopogon japonicus root, 600g of Codonopsis pilosula root, 300g of Poria cocos root, 300g of Prunus mume fruit, 150g of Astragalus membranaceus root, 150g of processed Astragalus membranaceus root, 300g of Glycyrrhiza uralensis root, 300g of Schisandra chinensis fruit, and 300g of Rehmannia glutinosa root. Extract and concentrate to obtain an extract. Add water to the extract and make up to 4000ml to obtain an extract solution. Add 10g of Eriobotrya japonica leaf powder, 28g of epigallocatechin gallate, 120g of instant soybean powder, 1g of corn oligopeptide powder, 1g of wheat oligopeptide powder, 1g of soybean peptide powder, 2g of PQQ, 100g of turmeric extract, and 0.2g of black pepper powder to the extract solution. Mix well and filter to obtain composition 9.

[0048] Composition 10: Take 450g of Trichosanthes kirilowii root, 450g of Pueraria lobata root, 300g of Ophiopogon japonicus root, 600g of Codonopsis pilosula root, 300g of Poria cocos root, 300g of Prunus mume fruit, 150g of Astragalus membranaceus root, 150g of processed Astragalus membranaceus root, 300g of Glycyrrhiza uralensis root, 300g of Schisandra chinensis fruit, and 300g of Rehmannia glutinosa root. Extract and concentrate to obtain an extract. Add water to the extract and make up to 4000ml to obtain an extract solution. Add 10g of Eriobotrya japonica leaf powder, 28g of epigallocatechin gallate, 120g of instant soybean powder, 1g of corn oligopeptide powder, 1g of wheat oligopeptide powder, 1g of soybean peptide powder, 24g of ginseng extract, 100g of turmeric extract, and 0.2g of black pepper powder to the extract solution. Mix well and filter to obtain composition 10.

[0049] Composition 11: Take 450g of Trichosanthes kirilowii root, 450g of Pueraria lobata root, 300g of Ophiopogon japonicus root, 600g of Codonopsis pilosula root, 300g of Poria cocos root, 300g of Prunus mume fruit, 150g of Astragalus membranaceus root, 150g of processed Astragalus membranaceus root, 300g of Glycyrrhiza uralensis root, 300g of Schisandra chinensis fruit, and 300g of Rehmannia glutinosa root. Extract and concentrate to obtain an extract. Add water to the extract and make up to 4000ml to obtain an extract solution. Add 10g of Eriobotrya japonica leaf powder, 28g of epigallocatechin gallate, 120g of instant soybean powder, 1g of corn oligopeptide powder, 1g of wheat oligopeptide powder, 1g of soybean peptide powder, 24g of ginseng extract, and 2g of PQQ to the extract solution. Mix evenly and filter to obtain composition 11.

[0050] Composition 12: Take 450g of Trichosanthes kirilowii root, 450g of Pueraria lobata root, 300g of Ophiopogon japonicus root, 600g of Codonopsis pilosula root, 300g of Poria cocos root, 300g of Prunus mume fruit, 150g of Astragalus membranaceus root, 150g of processed Astragalus membranaceus root, 300g of Glycyrrhiza uralensis root, 300g of Schisandra chinensis fruit, and 300g of Rehmannia glutinosa root. Extract and concentrate to obtain an extract. Add water to the extract and make up to 4000ml to obtain an extract solution. Add 10g of Eriobotrya japonica leaf powder, 28g of epigallocatechin gallate, 120g of instant soybean powder, 1g of corn oligopeptide powder, 1g of wheat oligopeptide powder, 1g of soybean peptide powder, 24g of ginseng extract, 2g of PQQ, 100g of turmeric extract, and 0.2g of black pepper powder to the extract solution. Mix well and filter to obtain composition 12.

[0051] Dosage and administration: 40ml each time, once a day.

[0052] Source: Loctite Pharmaceutical Co., Ltd.

[0053] 1.2.2 Positive control drug 1

[0054] Name: Metformin

[0055] Clinical use and dosage: Oral administration, starting with 0.5g twice daily; or 0.85g once daily with meals. Increase by 0.5g weekly, or 0.85g every two weeks, gradually increasing to 2g daily (for optimal blood sugar control), divided into multiple doses. The maximum recommended adult dose is 2550mg daily (i.e., 0.85g three times daily).

[0056] Source: Shanghai Yuanye Biotechnology Co., Ltd.

[0057] 1.2.3 Positive control drug 2

[0058] Name: Atorvastatin Calcium Tablets

[0059] Clinical use and dosage: Oral administration, the usual starting dose is 10 to 20 mg once daily. As treatment progresses, the physician may adjust the dosage based on the patient's response to achieve the best effect.

[0060] Source: Qilu Pharmaceutical Co., Ltd.

[0061] 2. Experimental Procedure

[0062] 2.1 Model Preparation

[0063] After 5 days of acclimatization, rats were fasted but allowed free access to water for 12 hours. Their body weight and fasting blood glucose were measured. Rats with a fasting blood glucose (FBG) value of less than 11.1 mmol / L were selected as normal rats and randomly grouped according to body weight for model preparation.

[0064] A diabetic rat model was established using a high-fat diet combined with a low-dose intraperitoneal injection of streptozotocin. Rats were fed a high-fat diet for 4 weeks, supplemented with fat emulsion (10 mL / kg) starting from week 3. After 4 weeks of this high-fat diet and fat emulsion regimen, rats were fasted for 12 hours but allowed free water, followed by an intraperitoneal injection of a low dose of streptozotocin. Two days later, after another 12-hour fasting period with free water, fasting blood glucose (FBG) was measured. A second low-dose intraperitoneal injection of streptozotocin was administered, followed by another 3 days of fasting. FBG was then measured again after the same 12-hour fasting period. During the model establishment process, the rats' hair and mental state were observed, and relevant experimental data were measured weekly.

[0065] 2.2 Model Evaluation

[0066] The body weight, food intake, water intake, urine output, and fasting blood glucose (FBG) of rats were measured. The model was considered to be successfully established when rats exhibited polyphagia, polydipsia, polyuria, and weight loss, and the FBG value was greater than 11.10 mmol / L.

[0067] 2.3 Grouping and administration of experimental animals

[0068] Grouping: Based on the principle of randomization, the successfully prepared diabetic rats were divided into a model group and a drug administration group, with 12 rats in each group. At the same time, 12 rats with normal blood glucose were selected as a blank group.

[0069] Dosage: Administer the prescribed dose once daily for 12 weeks.

[0070] Example 1

[0071] Effects of the drug composition on pancreatic β-cell function in T2DM model rats

[0072] To verify whether the composition of this invention has a regulatory effect on pancreatic β-cell function and whether its effect can achieve the expected results, it was applied to T2DM model rats and compared with the model group and positive control group 1 to observe whether its regulatory effect on pancreatic β-cell function is sustained. The test results after 12 weeks of continuous administration are shown in Table 1 below.

[0073] Table 1. Results of the regulation of pancreatic β-cell function in rats after 12 weeks of drug administration.

[0074]

[0075] Conclusion: The compositions of this invention have a good regulatory effect on pancreatic β-cells in T2DM rats. The insulin resistance index of rats in all groups showed a decreasing trend, and pancreatic β-cell function steadily improved. Compared with the model group, after 12 weeks of administration, the insulin resistance index of rats in Composition 1 and Compositions 5-12 groups was significantly reduced (P<0.05), and pancreatic β-cell function was significantly improved (P<0.05). The insulin resistance index of rats in Compositions 7-12 groups was extremely significantly reduced (P<0.01), and pancreatic β-cell function was extremely significantly improved (P<0.01). Comparing the pancreatic β-cell function data of Compositions 5 and 7, it can be seen that the efficacy of Composition 5 decreased by 37.12% after removing turmeric extract and black pepper powder. The mass proportion of turmeric extract and black pepper powder in the formulation was 2.6%. The synergistic effect was significant. Comparing the pancreatic β-cell function data of Composition 5 and Composition 8, it was found that the efficacy of Composition 5 decreased by 38.78% after the removal of ginseng extract, but the increased mass proportion of ginseng extract was only 0.63%, indicating an excellent synergistic effect between ginseng extract and Composition 5. Comparing the pancreatic β-cell function data of Composition 8 and Composition 11, it was found that the efficacy of Composition 8 decreased by 3.15% after the removal of PQQ, and the mass proportion of the synergistic component PQQ in the formulation was only 0.05%, indicating an excellent synergistic effect between PQQ and Composition 8. The repair effect of Composition 12 on pancreatic β-cell function was far greater than the sum of Composition 2 and Composition 5, indicating a significant synergistic effect between the synergistic component and Composition 5. Comprehensive comparison revealed that the pancreatic β-cell regulatory effects of Compositions 7-12 were excellent and superior to the positive control group, especially Compositions 7, 8, 11, and 12, which showed the best regulatory effects. Long-term use did not show drug resistance, demonstrating excellent pancreatic β-cell repair effects.

[0076] Example 2

[0077] Effects of the drug composition on changes in body weight in T2DM model rats

[0078] To investigate the other beneficial effects of the composition of this invention besides its regulatory effect on blood glucose, it was used in a rat model experiment for T2DM (type 2 diabetes mellitus) along with a positive control group to determine whether it could improve the weight gain of diabetic patients. The results after 12 weeks of continuous administration are shown in Table 2 below.

[0079] Table 2. Results of body weight changes in rats in each group after 12 weeks of drug administration.

[0080]

[0081] Conclusion: The body weight of rats in the treatment groups gradually increased from week 1 of administration until week 12, with continuous weight increase in all groups. Compared with the model group, the body weight of rats in the treatment groups showed a highly significant increase at week 4 (P<0.01) and week 8 (P<0.01). After 12 weeks of administration, the body weight increase was most significant in groups 7-12 of this application, all higher than that in the positive control group. Meanwhile, group 11 of this application showed the best weight recovery effect; compared with the model group, the weight recovery rate of group 11 was 29.4% higher than that of the positive control group. This indicates that the composition of this application has the best effect on body weight, demonstrating a good weight recovery effect.

[0082] Example 3

[0083] Effect of drug composition on changes in food intake in T2DM model rats

[0084] To investigate the other beneficial effects of the composition of the present invention besides its regulatory effect on blood glucose, it was used in a rat model of type 2 diabetes mellitus (T2DM) along with a positive control group to determine whether it could improve the reduced food intake in diabetic patients. The results after 12 weeks of continuous administration are shown in Table 3 below.

[0085] Table 3. Results of food intake changes in rats in each group after 12 weeks of drug administration.

[0086]

[0087] Conclusion: The food intake of the composition of the present invention showed a significant difference from the model group starting at week 4 of administration (P<0.05), and a highly significant difference after week 12 of administration (P<0.01). Compared with the positive control group, the food intake of groups 7-12 of the composition was less than that of the positive control group, demonstrating that its effect on regulating food intake in T2DM model rats was higher than that of the positive control group, and the effect of groups 3 and above was close to that of the blank group. The experimental results show that the composition of the present invention can effectively reduce food intake in T2DM patients.

[0088] Example 4

[0089] Effect of drug composition on changes in water intake in T2DM model rats

[0090] To investigate the other beneficial effects of the composition of this invention besides its blood glucose regulation effect, it was used in a rat model of type 2 diabetes mellitus (T2DM) to determine whether it could improve the reduced water intake in diabetic patients. The results after 12 weeks of continuous administration are shown in Table 4 below.

[0091] Table 4. Results of water intake changes in rats in each group after 12 weeks of drug administration.

[0092]

[0093] Conclusion: The results of water intake changes in rats during the T2DM model preparation period showed that water intake in the experimental model group rats continuously increased during the administration of a high-sugar, high-fat diet, and gradually decreased after drug administration. The water intake of the composition of this invention was significantly different from that of the model group after week 12 of administration (P<0.01). Compositions 6-12 of this invention showed significant regulatory effects on the decrease in water intake in T2DM model rats, all superior to the positive control group, and composition 11 showed a 1.5-fold higher regulatory effect on water intake. This indicates that the composition of this invention can effectively improve the symptoms of increased water intake in diabetic patients.

[0094] Example 5

[0095] Effects of the drug composition on changes in urine output in T2DM model rats

[0096] To investigate other beneficial effects of the composition of this invention besides its blood glucose regulation effect, it was used in a rat model of type 2 diabetes mellitus (T2DM) along with a positive control group to determine whether it could improve the reduction in urine output in diabetic patients. The results after 12 weeks of continuous administration are shown in Table 5 below.

[0097] Table 5. Results of urine output changes in rats in each group after 12 weeks of drug administration.

[0098]

[0099] Conclusion: During the administration period, urine output in the model group rats showed a continuous increasing trend. After administration, urine output in groups 5-12 and the positive control group decreased significantly from week 4 (P<0.05), and decreased extremely significantly at week 12 (P<0.01). The composition group of the present invention showed the best effect in reducing urine output. After 12 weeks of administration, the composition group of the present invention had a better effect on regulating urine output than the positive control group, and the urine output reduction effect of composition group 11 was 17.8% higher than that of the positive control group. This indicates that the composition has a significant effect on reducing urine output, and the effect becomes more significant over time.

[0100] Example 6

[0101] Effects of the drug composition on changes in blood lipids in T2DM model rats

[0102] To determine whether the composition of the present invention is effective in hyperlipidemic rats, a hyperlipidemic rat model was established, and changes in total cholesterol, triglycerides, and high-density lipoprotein were recorded after administration. The changes in blood lipids in rats were compared with those in the model group and the positive drug group. The test results after 12 weeks of continuous administration are shown in Table 6 below.

[0103] Table 6. Results of blood lipid changes in rats in each group after 12 weeks of drug administration.

[0104]

[0105] Total cholesterol (TC) refers to the sum of cholesterol contained in all lipoproteins in the blood, including free cholesterol and cholesterol esters. High total cholesterol reflects abnormal lipid metabolism. Long-term high levels of total cholesterol lead to cholesterol metabolism disorders, which are closely related to insulin resistance and are one of the important mechanisms in the development of type 2 diabetes mellitus (T2DM). Triglycerides (TG) are formed by the esterification of glycerol and three fatty acid molecules. They are the main form of energy storage in the human body and a major component of dietary fat, and are an important indicator of health. Hypertriglyceridemia is not only a common complication of T2DM, but may also further aggravate insulin resistance, forming a vicious cycle. High-density lipoprotein (HDL) is a serum protein, a complex lipoprotein composed of lipids, proteins, and their regulatory factors. HDL can rescue damaged angiogenesis in T2DM through various mechanisms. Low-density lipoprotein (LDL) is a lipoprotein in the blood, mainly responsible for transporting cholesterol from the liver to peripheral tissue cells, and is one of the main carriers of cholesterol. In patients with type 2 diabetes mellitus (T2DM), regular monitoring of low-density lipoprotein (LDL) helps in the early identification of the risk of atherosclerosis and can also serve as an indicator for evaluating the effectiveness of lipid-lowering drugs. Free fatty acids (FFA) are lipids present in the human body and are one of the substances derived from the breakdown of neutral fats. High FFA stimulation results in increased production of highly reactive reactive oxygen species (ROS) and reactive nitrogen species (RNS), thereby initiating oxidative stress mechanisms and activating multiple stress-sensitive signaling pathways within cells. These signaling pathways are closely related to insulin resistance and impaired β-cell function. The detection of the above five lipid-related indicators can comprehensively reveal information about changes in blood lipid levels in rats.

[0106] Conclusion: The results showed that compared with the model group, the serum levels of TC, TG, LDL-C, and FFA in rats in the composition 6-12 groups were significantly decreased (P<0.05), while the serum HDL-C level was significantly increased (P<0.01). The serum levels of TC, TG, LDL-C, and FFA in rats in the composition 7, 8, 11, and 12 groups were all significantly decreased (P<0.01), while the HDL-C level was significantly increased (P<0.01). Compared with the positive control group, the serum levels of TC, TG, LDL-C, FFA, and HDL-C in rats in the composition 6-12 groups were significantly different. Comparing the pancreatic β-cell function data of Composition 5 and Composition 7, it can be seen that the efficacy of Composition 5 decreased by 37.12% after the removal of turmeric extract and black pepper powder. The mass proportion of turmeric extract and black pepper powder in the formulation was 2.6%, showing a significant synergistic effect. Comparing the pancreatic β-cell function data of Composition 5 and Composition 8, it can be seen that the efficacy of Composition 5 decreased by 38.78% after the removal of ginseng extract. However, the mass proportion of ginseng extract increased by only 0.63%, indicating that ginseng extract and Composition 5 showed excellent synergistic effects and significant synergistic effects. Comparing the pancreatic β-cell function data of Composition 8 and Composition 11, it can be seen that the efficacy of Composition 8 decreased by 3.15% after the removal of PQQ. The mass proportion of the synergistic component PQQ in the formulation was only 0.05%, indicating that PQQ and Composition 8 had excellent synergistic effects. The repair effect of Composition 12 on pancreatic β-cell function was much higher than the sum of Composition 2 and Composition 5, indicating that the synergistic component had a significant synergistic effect with Composition 5. In summary, the effect of the composition on restoring lipid-related indicators in rat serum was higher than that in the positive control group, indicating that the composition of the present invention can effectively improve lipid indicators. Furthermore, a comparison of the pancreatic β-cell function repair data with the above data shows that the composition with good pancreatic β-cell function repair effect also has good lipid level regulation. Since pancreatic β-cells are the main cells producing insulin, this further verifies that lipids are directly regulated by insulin; that is, improving pancreatic β-cell function can effectively indirectly regulate lipid levels.

[0107] Example 7

[0108] Effects of the drug composition on liver function indicators in T2DM model rats

[0109] Because patients with diabetes and hyperlipidemia are in a state of high sugar and high fat for a long time, they are prone to liver overload, leading to diabetic liver disease, fatty liver, and other conditions. Therefore, liver indicators of the composition of this invention were monitored during the treatment of hyperglycemia and hyperlipidemia to determine whether it would cause liver damage. The test results after 12 weeks of continuous administration are shown in Table 7 below.

[0110] Table 7. Results of liver function indicators in rats of each group after 12 weeks of drug administration.

[0111]

[0112] Serum alanine aminotransferase (ALT) is mainly found in hepatocytes. When hepatocytes are damaged, ALT is released into the blood in large quantities, leading to elevated levels. Therefore, ALT testing is an important indicator for assessing the presence and extent of liver damage. Alkaline phosphatase (ALP) is mainly found in hepatic cholangiocarcinoma cells, and elevated serum ALP levels often indicate biliary system damage or liver fibrosis. In type 2 diabetes, ALP levels are closely related to insulin resistance and glucose and lipid metabolism disorders. Aspartate aminotransferase (AST) is an aminotransferase that catalyzes the aminotransfer reaction between aspartate and α-ketoglutarate to produce oxaloacetate and glutamate. Elevated AST reflects severe hepatocyte damage or a tendency towards cirrhosis. Total protein (TP), as an important indicator of liver function, has multidimensional assessment value in diabetic rat models. TP is composed of albumin (reflecting liver synthetic function) and globulin (related to immune inflammation), and its level changes can comprehensively reflect liver damage and systemic metabolic disorders caused by diabetes. Total bilirubin (TBIL) is an important indicator for assessing the liver's ability to process bilirubin. When liver cells are damaged, such as in cases of hepatitis, cirrhosis, or toxic hepatitis, the liver is unable to metabolize bilirubin normally, leading to elevated total bilirubin levels. Monitoring these indicators can provide a comprehensive assessment of liver function in rats.

[0113] Conclusion: The experimental data showed that compared with the model group, the overall liver function levels in the composition 6-12 groups were significantly different, with extremely significant decreases in ALT, ALP, AST, and BTIL levels (P<0.01) and extremely significant increases in TP level (P<0.01). The overall liver function levels in the composition 6-12 groups were better than those in the positive control group and were very close to those in the disease-free blank group. Comparing the ALT, ALP, AST, TP, and TBIL data of Composition 5 and Composition 7, it can be seen that the recovery effect of each liver index decreased after removing turmeric extract and black pepper powder from Composition 5, by 32.97%, 28.82%, 7.31%, 19.7%, and 28.68%, respectively. The mass percentage of turmeric extract and black pepper powder in the formulation is 2.6%. The decrease in efficacy after removing turmeric extract and black pepper powder is far greater than twice the mass percentage of these two ingredients, indicating that turmeric extract and black pepper powder have a significant synergistic effect as enhancing components. Comparing the ALT, ALP, AST, TP, and TBIL data of Composition 5 and Composition 8, it can be seen that the recovery effect of each liver index was not ideal after removing ginseng extract from Composition 5, decreasing by 33%. The proportions of ginseng extract in the formulations were 0.81%, 30.99%, 7.73%, 20.06%, and 30.24%, respectively. Ginseng extract accounted for only 0.63% of the total composition, and the decrease in efficacy after removing ginseng extract was more than twice that of its proportion, indicating a highly effective synergistic effect between ginseng extract and composition 5. Comparing the ALT, ALP, AST, TP, and TBIL data of composition 8 and composition 11, it was found that the efficacy of composition 8 decreased by 1.69%, 0.57%, 1.09%, 2.79%, and 1.30% respectively after removing PQQ. The synergistic component PQQ accounted for only 0.05% of the total composition, and the decrease in efficacy after removing PQQ was more than twice that of its proportion, indicating a significant synergistic effect between PQQ and composition 8. These experiments demonstrate that the compositions of this invention have a good effect on restoring liver function, indicating a significant protective effect on the liver. Comparison of pancreatic β-cell function and liver indicators showed that groups with excellent improvement in pancreatic β-cell function also showed a synchronous increase in liver regulation levels. Data results demonstrate that improved pancreatic β-cell function indirectly repairs liver damage. By optimizing insulin secretion and action, it restores the balance of glucose and lipid metabolism throughout the body, reducing the burden on the liver and fat accumulation caused by "metabolic disorders" from the source, ultimately protecting the liver.

[0114] Example 8

[0115] Effects of the drug composition on renal function indicators in T2DM model rats

[0116] Because patients with diabetes and hyperlipidemia are in a state of high sugar and high fat for a long time, they are prone to kidney overload, leading to diabetic nephropathy, nephrotic syndrome, and other conditions. Therefore, the renal indicators of the composition of this invention were monitored during the treatment of hyperglycemia and hyperlipidemia to determine whether it would cause kidney damage. The test results after 12 weeks of continuous administration are shown in Table 8 below.

[0117] Table 8. Results of renal function indicators in rats of each group after 12 weeks of drug administration.

[0118]

[0119] Creatinine (CRE) is a metabolic byproduct of muscle metabolism in the human body, primarily excreted through glomerular filtration. Serum creatinine levels are an important indicator of glomerular filtration function; when the glomerular filtration rate decreases, the kidneys' ability to excrete creatinine declines, leading to an increase in serum creatinine concentration. Endothelin-1 (ET-1) is produced by vascular endothelial cells. Physiologically, it is a potent vasoconstrictive peptide that regulates vasodilation to maintain cardiovascular homeostasis and can also activate receptors to regulate cell proliferation. Clinically, it is associated with cardiovascular disease risk and reflects the degree of endothelial dysfunction in diseases such as diabetes and hypertension. Blood urea nitrogen (BUN), as a final product of protein metabolism, is a non-protein nitrogen compound. Its small molecular weight and lack of binding to plasma proteins allow for free glomerular filtration; therefore, serum BUN concentration is a key indicator for assessing glomerular filtration function. In patients with diabetic nephropathy, decreased glomerular filtration rate leads to impaired BUN excretion and significantly elevated serum concentrations. This change can serve as an important biological marker for early identification of diabetic kidney damage and monitoring the progression of renal function. Nitric oxide (NO), a key vasoactive substance synthesized by endothelial cells, maintains renal function by regulating glomerular vascular tone and hemodynamics. Decreased NO levels not only reflect hyperglycemia-induced oxidative stress damage and endothelial dysfunction but are also closely related to renal tissue inflammation, fibrosis, and hemodynamic abnormalities. Furthermore, NO metabolic imbalance can serve as a biomarker for assessing oxidative stress status and identifying potential therapeutic targets, and can act as an early warning signal for diabetic nephropathy.

[0120] Conclusion: Comprehensive analysis of renal function indicators in each composition group revealed significant differences in the recovery effects on renal function among the different composition groups, with the 7-12 composition group showing the most significant effect. Compared with the model group, the serum levels of CRE, ET-1, and BUN in the composition group rats were significantly decreased (P<0.01), while the NO level was significantly increased compared with the model group (P<0.05), demonstrating that the compositions of this invention have a good nephroprotective effect. Comparing the CRE, ET-1, BUN, and NO data of Composition 5 and Composition 7, it can be seen that the recovery effect of each kidney index of Composition 5 decreased significantly after the removal of turmeric extract and black pepper powder, by 34.75%, 6.42%, 34.15%, and 6.98%, respectively. The mass proportion of turmeric extract and black pepper powder in the formulation is 2.6%. The decrease in efficacy after removing turmeric extract and black pepper powder is far more than twice that of their mass proportion, indicating that turmeric extract and black pepper powder have a significant synergistic effect as enhancing ingredients. Comparing the CRE, ET-1, BUN, and NO data of Composition 5 and Composition 8, it can be seen that the recovery effect of each kidney index of Composition 5 after the removal of ginseng extract is not ideal, decreasing by 37.41%, respectively. The proportions of ginseng extract in the formulations were 7.03%, 47.17%, and 5.88%, respectively. The ginseng extract accounted for only 0.63% of the total mass of the formulations. The decrease in efficacy after removing ginseng extract was more than twice the proportion of its mass, indicating a significant synergistic effect between ginseng extract and composition 5 on kidney repair indicators. Comparing the CRE, ET-1, BUN, and NO data of composition 8 and composition 11, it was found that the efficacy of composition 8 decreased by 2.54%, 1.25%, 3.96%, 3.96%, and 3.41% respectively after removing PQQ. The synergistic component PQQ accounted for only 0.05% of the total mass of the formulations. The decrease in efficacy after removing PQQ was more than twice the proportion of its mass, indicating a significant synergistic effect between PQQ and composition 8. Furthermore, the composition group of this invention showed better kidney protection than the positive control group. Comparison of pancreatic β-cell function and kidney indicators showed that the group with excellent improvement in pancreatic β-cell function also showed a simultaneous increase in kidney regulation level. Regulating pancreatic β-cell function can effectively reduce kidney damage and has a positive effect on kidney protection.

[0121] Example 9

[0122] Effects of the drug composition on inflammatory markers in T2DM model rats

[0123] Based on the pathological reasons why diabetic patients are prone to complications, it is known that the main cause is the decline in bodily function and the increase in the level of inflammatory factors in the body, leading to inflammation in multiple tissues and causing symptoms such as peripheral neuropathy, diabetic retinopathy, diabetic nephropathy, and diabetic autonomic neuropathy. To verify whether the composition of this invention has an anti-inflammatory effect during treatment, inflammation data were monitored in T2DM model rats to ensure the efficacy of drug treatment. The test results after 12 weeks of continuous administration are shown in Table 9 below.

[0124] Table 9. Results of inflammatory-related markers in rats of different groups after 12 weeks of drug administration.

[0125]

[0126] Tumor necrosis factor-α (TNF-α) is a 17-kDa protein composed of 157 amino acids that plays a crucial role in apoptosis and survival, as well as in immunity and inflammation. It induces tissue-specific inflammation by participating in ROS production and activating various transcriptional pathways. Interleukin-1β (IL-1β) is an important cytokine primarily involved in immune regulation and inflammatory responses. It is a key mediator in inflammatory responses, inducing the synthesis of other inflammatory cytokines (such as IL-6), chemokines, adhesion molecules, and acute-phase proteins. Serum high-sensitivity C-reactive protein (hs-CRP) is a C-reactive protein measured using a highly sensitive detection technique and is used to detect low-grade inflammation. Insulin resistance is often accompanied by a chronic low-grade inflammatory state, which may originate from various inflammatory mediators released from adipose tissue. These mediators stimulate the liver to synthesize CRP through signal transduction, leading to elevated hs-CRP levels.

[0127] Conclusion: The results showed that the levels of inflammatory factors in the model group were significantly higher than those in the control group. Comprehensive analysis of the inflammatory factor indicators in the composition groups revealed that the levels of inflammatory factors in the composition groups of this invention were lower than those in the positive control group, indicating better efficacy. Compared with the model group, the levels of TNF-α, IL-1β, and hs-CRP in rats in the composition 6-12 groups were significantly decreased (P<0.01). Comparison of TNF-α, IL-1β, and hs-CRP data between Composition 5 and Composition 7 showed that the levels of each inflammatory factor in Composition 5 significantly increased after the removal of turmeric extract and black pepper powder, by 7.83%, 10.95%, and 7.20%, respectively. The mass percentage of turmeric extract and black pepper powder in the formulation was 2.6%, and the decrease in efficacy after removing them was more than twice that of their combined mass percentage, indicating a significant synergistic effect between turmeric extract, black pepper powder, and Composition 5. Comparison of TNF-α, IL-1β, and hs-CRP data between Composition 5 and Composition 8 showed that the recovery effect of each inflammatory factor in Composition 5 was not ideal after the removal of ginseng extract, with increases of 4... The proportions of ginseng extract in the formulations were 0.89%, 12.21%, and 8.06%, respectively. The ginseng extract accounted for only 0.63% of the total composition, and the decrease in efficacy after removing it was more than twice the proportion of ginseng extract, indicating a significant synergistic effect between ginseng extract and composition 5 on inflammatory markers. Comparing the TNF-α, IL-1β, and hs-CRP data of composition 8 and composition 11, it was found that the efficacy of composition 8 decreased by 0.54%, 1.67%, and 1.74% respectively after removing PQQ. The synergistic component PQQ accounted for only 0.05% of the total composition, and the decrease in efficacy after removing PQQ was more than twice the proportion of PQQ, indicating a significant synergistic effect between PQQ and composition 8. This demonstrates that the compositions of the present invention have good anti-inflammatory effects.

[0128] Example 10

[0129] Effects of the drug composition on oxidative stress-related indicators in T2DM model rats

[0130] To investigate whether the pharmaceutical composition would cause oxidative damage in treating T2DM model rats, oxidative stress-related indicators were measured in each treatment group and the model group during the experiment to verify the safety of using the composition of the present invention. The test results after 12 weeks of continuous administration are shown in Table 10 below.

[0131] Table 10 Results of oxidative stress-related indicators in rats of each group after 12 weeks of drug administration

[0132]

[0133] Malondialdehyde (MDA) is a product of lipid peroxidation and can reflect the level of oxidative stress in the body.

[0134] Elevated levels indicate increased free radical production and impaired antioxidant defense systems in patients. Superoxide dismutase (SOD) is an antioxidant metalloenzyme present in the body, playing a crucial role in the balance between oxidation and antioxidation. SOD can increase insulin secretion, promote glucose utilization, inhibit the breakdown and release of glycogen in the liver, and protect the function and number of pancreatic β cells by scavenging free radicals. Glutathione peroxidase (GSH-Px) is an important antioxidant enzyme. In diabetic states, due to increased oxidative stress caused by hyperglycemia, changes in GSH-Px activity can reflect the strength of the body's antioxidant defense capabilities; GSH-Px activity is typically reduced in diabetic rats.

[0135] Conclusion: Through comprehensive analysis of oxidative stress indicators in each treatment group, it was found that the oxidative stress level in groups 7-12 of the present invention was lower than that in the positive control group, and the efficacy was the best. Compared with the model group, the serum MDA level of rats in groups 5-12 of the present invention was significantly decreased (P<0.01), while the SOD and GSH-Px levels were significantly increased (P<0.01). Comparison of GSH-Px, MDA, and SOD data between composition 5 and composition 7 shows that the oxidative stress level of composition 5 was significantly reduced after the removal of turmeric extract and black pepper powder, changing to 10.85%, 43.48%, and 8.19%, respectively. The mass proportion of turmeric extract and black pepper powder in the formulation was 2.6%. The decrease in efficacy after the removal of turmeric extract and black pepper powder was more than twice that of their mass proportion, indicating that turmeric extract and black pepper powder have a significant synergistic effect with composition 5. Comparison of GSH-Px, MDA, and SOD data between composition 5 and composition 8 shows that the recovery effect of each oxidative stress index of composition 5 was not ideal after the removal of ginseng extract, changing to 12. The proportions of ginseng extract in the formulations were 0.09%, 50.00%, and 9.83%, respectively. The ginseng extract accounted for only 0.63% of the total composition, and the decrease in efficacy after removing it was more than twice the proportion of ginseng extract by weight, indicating a significant synergistic effect between ginseng extract and composition 5 in terms of antioxidant indicators. Comparing the GSH-Px, MDA, and SOD data of composition 8 and composition 11, it was found that the efficacy of composition 8 changed by 2.98%, 8.64%, and 2.45% respectively after removing PQQ. The synergistic component PQQ accounted for only 0.05% of the total composition, and the decrease in efficacy after removing PQQ was more than twice the proportion of PQQ by weight, indicating a significant synergistic effect between PQQ and composition 8. The experimental results show that the compositions of this invention have a highly efficient regulatory effect on oxidative stress-related indicators, exhibiting good antioxidant properties.

[0136] in conclusion:

[0137] 1. The composition of the present invention is composed of Trichosanthes kirilowii root, Pueraria lobata root, Ophiopogon japonicus root, Codonopsis pilosula root, Poria cocos root, Prunus mume fruit, Astragalus membranaceus root, processed Astragalus membranaceus root, Glycyrrhiza uralensis root, Schisandra chinensis fruit, Rehmannia glutinosa root, Eriobotrya japonica leaf powder, epigallocatechin gallate, instant soybean powder, corn oligopeptide powder, wheat oligopeptide powder, and soybean peptide powder. The composition also contains synergistic ingredients, which are one or more of ginseng extract, PQQ, turmeric extract, and black pepper powder. The results of examining the effects of multiple compositions on β-cell function, body weight, food intake, water intake, urine output, blood lipids, liver and kidney function, inflammation, and oxidative stress indicate that the synergistic components enhance efficacy, but the synergistic effects vary significantly. The combination of ginseng and PQQ exhibits excellent synergistic effects, with composition 11 demonstrating the best therapeutic effect. PQQ shows weak antagonistic effects with turmeric extract and black pepper powder, and composition 9 shows a lower effect on the correction of various indicators compared to composition 7. Ginseng, turmeric extract, and black pepper powder also show weak antagonistic effects, and composition 10 shows a slightly lower effect on the correction of various indicators compared to composition 8. Overall, however, the compositions of this invention can effectively adjust the values ​​of each indicator to near the values ​​of the blank control group, indicating that the compositions of this invention can effectively treat various diseases and complications caused by abnormalities in the aforementioned indicators.

[0138] 2. The composition of this invention has an excellent repairing effect on pancreatic β cells, significantly improving their function, reducing the insulin resistance index, increasing insulin secretion, and regulating the number of pancreatic β cells in the body. It can also reduce food intake, water intake, and urine output, increase weight, and alleviate the "three highs and one low" symptoms in diabetic patients, significantly improving weight and outperforming the positive control drug metformin. It can significantly reduce food intake, with a clearly obvious improvement compared to the model group; and it can significantly reduce water intake, showing excellent results compared to both the model group and the positive control group. In the pancreatic β-cell function experiment, the synergistic components turmeric extract and black pepper powder in composition 7 accounted for 2.6% of the total mass. The decrease in efficacy after removing turmeric extract and black pepper powder was more than twice the mass percentage of these two components. Similarly, the ginseng extract in composition 8 accounted for only 0.63% of the total mass, and the decrease in efficacy after removing ginseng extract was far more than twice the mass percentage of ginseng extract. In composition 11, the synergistic component PQQ accounted for only 0.05% of the total mass, and the decrease in efficacy after removing PQQ was far more than twice the mass percentage of PQQ. Composition 12 showed a significantly greater restorative effect on pancreatic β-cell function than the sum of compositions 2 and 5, indicating a significant synergistic effect between the synergistic components and composition 5. The results indicate that turmeric extract, black pepper powder, ginseng extract, PQQ, trichosanthes root, kudzu root, ophiopogon root, codonopsis root, poria cocos, dried plum, astragalus root, processed astragalus root, licorice root, schisandra fruit, rehmannia root, loquat leaf powder, epigallocatechin gallate, instant soy powder, corn oligopeptide powder, wheat oligopeptide powder, and soybean peptide powder have significant synergistic effects in improving pancreatic β-cell function.

[0139] 3. Comparing liver and kidney related index information in the comparative experiment, when pancreatic β-cell function is improved, the repair effect on the liver and kidneys—key target organs for insulin's metabolic regulation—is significant. In the liver and kidney repair experiment, the synergistic components turmeric extract and black pepper powder in composition 7 accounted for 2.6% of the total mass, and the decrease in efficacy after removing turmeric extract and black pepper powder was more than twice the mass percentage of the two components; the ginseng extract in composition 8 accounted for only 0.63% of the total mass, and the decrease in efficacy after removing ginseng extract was far more than twice the mass percentage of ginseng extract; the synergistic component PQQ in composition 11 accounted for only 0.05% of the total mass, and the decrease in efficacy after removing PQQ was far more than twice the mass percentage of PQQ. The results indicate that turmeric extract, black pepper powder, ginseng extract, PQQ, trichosanthes root, kudzu root, ophiopogon root, codonopsis root, poria cocos, dried plum, astragalus root, processed astragalus root, licorice root, schisandra fruit, rehmannia root, loquat leaf powder, epigallocatechin gallate, instant soy flour, corn oligopeptide powder, wheat oligopeptide powder, and soybean peptide powder have a significant synergistic effect in repairing liver damage. The composition of this invention has a good repairing effect on liver and kidney damage, completely avoiding drug-induced organ damage and maintaining normal organ function.

[0140] 4. Since blood lipids are directly regulated by insulin, the pharmaceutical composition of this invention regulates blood lipids by repairing the function of pancreatic β cells, providing a new and high-quality option for solving problems related to dyslipidemia. Simultaneously, the composition of this invention can also avoid other diseases caused by excessively high blood lipids. T2DM rats that ingested the composition of this invention showed good liver and kidney function, and the protective effect on the liver and kidneys was superior to the positive control group. In the blood lipid change experiment, the synergistic components turmeric extract and black pepper powder in composition 7 accounted for 2.6% of the total mass, and the decrease in efficacy after removing turmeric extract and black pepper powder was more than twice the mass percentage of these two components; the ginseng extract in composition 8 accounted for only 0.63% of the total mass, and the decrease in efficacy after removing ginseng extract was far more than twice the mass percentage of ginseng extract; the synergistic component PQQ in composition 11 accounted for only 0.05% of the total mass, and the decrease in efficacy after removing PQQ was far more than twice the mass percentage of PQQ. The results indicate that turmeric extract, black pepper powder, ginseng extract, PQQ, and trichosanthes root, kudzu root, ophiopogon root, codonopsis root, poria cocos, dried plum, astragalus root, processed astragalus root, licorice root, schisandra fruit, rehmannia root, loquat leaf powder, epigallocatechin gallate, instant soy flour, corn oligopeptide powder, wheat oligopeptide powder, and soybean peptide powder have a significant synergistic effect in lowering blood lipids. Experimental results confirm that the composition of this invention possesses excellent organ repair capabilities, with optimal liver tissue morphology and significant repair effects on kidney damage.

[0141] 5. Pharmacodynamic tests show that the compositions of this invention have a regulatory effect on inflammation-related indicators in rat serum, including a retrograde effect on the levels of IL-1, TNF-α, and hs-CRP. In the inflammation regulation experiment, the synergistic components turmeric extract and black pepper powder in composition 7 accounted for 2.6% of the total mass, and the decrease in efficacy after removing turmeric extract and black pepper powder was more than twice the mass percentage of the two components; the ginseng extract in composition 8 accounted for only 0.63% of the total mass, and the decrease in efficacy after removing ginseng extract was far more than twice the mass percentage of ginseng extract; the synergistic component PQQ in composition 11 accounted for only 0.05% of the total mass, and the decrease in efficacy after removing PQQ was far more than twice the mass percentage of PQQ. The results indicate that the synergistic effects of the synergistic components—turmeric extract, black pepper powder, ginseng extract, PQQ, trichosanthes root, kudzu root, ophiopogon root, codonopsis root, poria cocos, dried plum, astragalus root, processed astragalus root, licorice root, schisandra fruit, rehmannia root, loquat leaf powder, epigallocatechin gallate, instant soy powder, corn oligopeptide powder, wheat oligopeptide powder, and soybean peptide powder—are significant in reducing the inflammatory index. Overall, the high-dose group of the composition showed lower levels of inflammatory factors, superior to the positive control group, indicating that the composition of this invention has a positive anti-inflammatory effect while regulating pancreatic β-cells and hyperlipidemia.

[0142] 6. According to the pharmacodynamic test results, the composition of the present invention does not affect the oxidative stress function of normal organisms and has high safety. In the oxidative stress function test, the synergistic components turmeric extract and black pepper powder in composition 7 account for 2.6% of the total mass, and the decrease in efficacy after removing turmeric extract and black pepper powder is more than twice the mass percentage of the two components; the ginseng extract in composition 8 accounts for only 0.63% of the total mass, and the decrease in efficacy after removing ginseng extract is far more than twice the mass percentage of ginseng extract; the synergistic component PQQ in composition 11 accounts for only 0.05% of the total mass, and the decrease in efficacy after removing PQQ is far more than twice the mass percentage of PQQ. The results indicate that turmeric extract, black pepper powder, ginseng extract, PQQ, and trichosanthes root, kudzu root, ophiopogon root, codonopsis root, poria cocos, dried plum, astragalus root, processed astragalus root, licorice root, schisandra fruit, rehmannia root, loquat leaf powder, epigallocatechin gallate, instant soy powder, corn oligopeptide powder, wheat oligopeptide powder, and soybean peptide powder have a significant synergistic effect in antioxidant activity. Simultaneously, they exhibit a restorative effect on oxidative stress levels, showing better antioxidant effects compared to the positive control group. This indicates that the drug composition has a good resistance to oxidative stress, ensuring normal bodily function while treating diseases, without any potential residual risks.

Claims

1. A Tangluotai series composition with the functions of improving pancreatic β-cell function, regulating blood lipids, repairing liver and kidney damage, anti-inflammatory and antioxidant properties, characterized in that, The composition, by weight, comprises: 150-900 parts of Trichosanthes kirilowii root, 150-900 parts of Pueraria lobata root, 100-600 parts of Ophiopogon japonicus root, 200-1200 parts of Codonopsis pilosula root, 100-600 parts of Poria cocos root, 100-600 parts of Prunus mume fruit, 50-300 parts of Astragalus membranaceus root, 50-300 parts of processed Astragalus membranaceus root, 100-600 parts of Glycyrrhiza uralensis root, 100-600 parts of Schisandra chinensis fruit, and 100 parts of Rehmannia glutinosa root. The product consists of 600 parts of loquat leaf powder, 2-50 parts of epigallocatechin gallate, 5-140 parts of instant soy powder, 30-2000 parts of corn oligopeptide powder, 0.5-20 parts of wheat oligopeptide powder, 0.5-20 parts of soybean peptide powder, and synergistic ingredients; the synergistic ingredients are composed of one or more of the following: 5-120 parts of ginseng extract, 20-500 parts of turmeric extract, 0.4-10 parts of PQQ, and 0.1-5.0 parts of black pepper powder.

2. The Tangluotai series composition according to claim 1, which has the effects of improving pancreatic β-cell function, regulating blood lipids, repairing liver and kidney damage, anti-inflammatory and antioxidant properties, is characterized in that... The composition, by weight, comprises: 225-675 parts of Trichosanthes kirilowii root, 225-675 parts of Pueraria lobata root, 200-450 parts of Ophiopogon japonicus root, 400-900 parts of Codonopsis pilosula root, 200-450 parts of Poria cocos root, 200-450 parts of Prunus mume fruit, 100-225 parts of Astragalus membranaceus root, 100-225 parts of processed Astragalus membranaceus root, 200-450 parts of Glycyrrhiza uralensis root, 200-450 parts of Schisandra chinensis fruit, and 20 parts of Rehmannia glutinosa root. The product comprises 0-450 parts of loquat leaf powder, 5-20 parts of epigallocatechin gallate, 15-55 parts of instant soy powder, 80-1000 parts of corn oligopeptide powder, 0.5-10 parts of wheat oligopeptide powder, 0.5-10 parts of soybean peptide powder, and synergistic ingredients; the synergistic ingredients are composed of one or more of the following: 12-50 parts of ginseng extract, 50-200 parts of turmeric extract, 1.0-4.0 parts of PQQ, and 0.1-1.0 parts of black pepper powder.

3. A Tangluotai series composition according to claim 1 or 2, characterized in that it enhances pancreatic β-cell function, regulates blood lipids, repairs liver and kidney damage, and has anti-inflammatory and antioxidant properties. The composition, by weight, comprises 375-540 parts of Trichosanthes kirilowii root, 375-540 parts of Pueraria lobata root, 250-360 parts of Ophiopogon japonicus root, 500-720 parts of Codonopsis pilosula root, 250-360 parts of Poria cocos root, 250-360 parts of Prunus mume fruit, 125-180 parts of Astragalus membranaceus root, 125-180 parts of processed Astragalus membranaceus root, 250-360 parts of Glycyrrhiza uralensis root, 250-360 parts of Schisandra chinensis fruit, 250-360 parts of Rehmannia glutinosa root, 7-15 parts of Eriobotrya japonica leaf powder, 18-42 parts of epigallocatechin gallate, 100-500 parts of instant soy flour, 1-5 parts of corn oligopeptide powder, 1-5 parts of wheat oligopeptide powder, 1-5 parts of soybean peptide powder, and a synergistic ingredient; the synergistic ingredient comprises 15-35 parts of ginseng extract, 65-150 parts of turmeric extract, and PQQ. One or more of the following: 1.5-2.5 parts and 0.2-0.5 parts black pepper powder.

4. The Tangluotai series composition according to claim 3, which has the effects of improving pancreatic β-cell function, regulating blood lipids, repairing liver and kidney damage, anti-inflammatory and antioxidant properties, is characterized in that... The composition, by weight, comprises 450 parts of Trichosanthes kirilowii root, 450 parts of Pueraria lobata root, 300 parts of Ophiopogon japonicus root, 600 parts of Codonopsis pilosula root, 300 parts of Poria cocos root, 300 parts of Prunus mume fruit, 150 parts of Astragalus membranaceus root, 150 parts of processed Astragalus membranaceus root, 300 parts of Glycyrrhiza uralensis root, 300 parts of Schisandra chinensis fruit, 300 parts of Rehmannia glutinosa root, 10 parts of Eriobotrya japonica leaf powder, 28 parts of epigallocatechin gallate, 120 parts of instant soy flour, 1 part of corn oligopeptide powder, 1 part of wheat oligopeptide powder, 1 part of soybean peptide powder, and a synergistic ingredient; the synergistic ingredient is composed of one or more of the following: 24 parts of ginseng extract, 100 parts of turmeric extract, 2 parts of PQQ, and 0.2 parts of black pepper powder.

5. A method for preparing a Tangluotai series composition according to any one of claims 1 to 4, which has the effects of improving pancreatic β-cell function, regulating blood lipids, repairing liver and kidney damage, anti-inflammatory and antioxidant properties, characterized in that, The preparation method is as follows: (1) Weigh out the following ingredients according to weight: 150-900 parts of Trichosanthes kirilowii root, 150-900 parts of Pueraria lobata root, 100-600 parts of Ophiopogon japonicus root, 200-1200 parts of Codonopsis pilosula root, 100-600 parts of Poria cocos root, 100-600 parts of Prunus mume fruit, 50-300 parts of Astragalus membranaceus root, 50-300 parts of processed Astragalus membranaceus root, 100-600 parts of Glycyrrhiza uralensis root, 100-600 parts of Schisandra chinensis fruit, and 100-600 parts of Rehmannia glutinosa root. The mixture comprises 600 parts of loquat leaf powder, 2-50 parts of epigallocatechin gallate, 5-140 parts of instant soy powder, 30-2000 parts of corn oligopeptide powder, 0.5-20 parts of wheat oligopeptide powder, 0.5-20 parts of soybean peptide powder, and a synergistic ingredient; the synergistic ingredient is composed of one or more of the following: 5-120 parts of ginseng extract, 20-500 parts of turmeric extract, 0.4-10 parts of PQQ, and 0.1-5.0 parts of black pepper powder; for later use. (2) The weighed Trichosanthes kirilowii, Pueraria lobata, Ophiopogon japonicus, Codonopsis pilosula, Poria cocos, Prunus mume, Astragalus membranaceus, processed Astragalus membranaceus, Glycyrrhiza uralensis, Schisandra chinensis and Rehmannia glutinosa were extracted and concentrated to obtain an extract. The extract was diluted with water and stirred evenly to obtain an extract solution. (3) Loquat leaf powder, epigallocatechin gallate, instant soybean powder, corn oligopeptide powder, wheat oligopeptide powder and soybean peptide powder are added to the extract, mixed evenly and filtered to obtain a mixture. (4) Add one or more of ginseng extract, turmeric extract, PPQ and black pepper powder to the above mixture, mix evenly and filter to obtain the composition.

6. A method for preparing a Tangluotai series composition according to claim 5, which has the effects of improving pancreatic β-cell function, regulating blood lipids, repairing liver and kidney damage, anti-inflammatory and antioxidant properties, characterized in that, The composition also includes any pharmaceutically acceptable excipients.

7. A method for preparing a Tangluotai series composition according to claim 5 or 6, which has the effects of improving pancreatic β-cell function, regulating blood lipids, repairing liver and kidney damage, anti-inflammatory and antioxidant properties, characterized in that, The composition can be prepared into dosage forms including oral solutions, tablets, granules, capsules, injections, pills, oral liquids, and creams.

8. The application of the Tangluotai series compositions according to any one of claims 1 to 4, which have the effects of improving pancreatic β-cell function, regulating blood lipids, repairing liver and kidney damage, anti-inflammatory and antioxidant properties, is characterized in that... The composition is used as a drug to regulate insulin resistance index, alleviate symptoms and complications caused by a decrease in the number of pancreatic β cells, reduce fat levels in patients with hyperlipidemia, alleviate hyperlipidemia and its complications, repair liver, kidney and pancreatic damage caused during the treatment of hyperglycemia and hyperlipidemia, and / or alleviate complications caused by type 2 diabetes and hyperlipidemia.

9. The application according to claim 8, characterized in that, The regulation of the insulin resistance index is achieved by increasing the number of pancreatic β cells in patients with hyperglycemia.

10. The application according to claim 8, characterized in that, The aforementioned relief of indigestion, steatorrhea, weight loss, ketoacidosis and its complications caused by a decrease in the number of pancreatic β cells.

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