Compound medicine of scrophulariaceae, astragalus, panax and rehdium for preventing and treating diabetes and complications

Abstract

The application provides a traditional Chinese medicine compound medicine composed of Coptis chinensis, Astragalus membranaceus, Panax notoginseng and Rehmannia glutinosa and application thereof in preventing and treating diabetes and diabetes complications, and experimental results show that the compound medicine has good prevention and treatment effects on diabetes and various diabetes complications such as diabetic heart disease, diabetic kidney disease and diabetic retinopathy.

Description

Technical Field

[0001] This invention belongs to the fields of traditional Chinese medicine and diabetes treatment, specifically involving compound Chinese medicines of Coptis chinensis, Astragalus membranaceus, Panax notoginseng, and Rehmannia glutinosa, and their application in the prevention and treatment of diabetes and its complications. Background Technology

[0002] Diabetes mellitus is a metabolic disease characterized by chronically elevated blood glucose levels, caused by defects in insulin secretion and / or action. Its incidence and mortality rates are rising annually. According to the World Health Organization, the number of people with diabetes worldwide reached 176 million in 2000, and is projected to double to 370 million by 2030. Diabetes is not a single disease, but a syndrome caused by multiple factors, including genetic and environmental factors. Insulin is synthesized and secreted by pancreatic β-cells, circulates through the bloodstream to target cells in various tissues and organs, binds to specific receptors, and triggers intracellular metabolic effects. Abnormalities in any step of this process can lead to diabetes.

[0003] Long-term disorders of carbohydrate, fat, and protein metabolism can cause multi-system damage, leading to chronic progressive lesions, functional decline, and failure of organs and tissues such as the eyes, kidneys, nerves, heart, and blood vessels. In severe cases or under stress, acute and severe metabolic disorders can occur, which are the complications of diabetes. Chronic complications of diabetes can affect all vital organs throughout the body, and their pathogenesis is extremely complex and not yet fully understood. Currently, it is believed to be related to the interaction of multiple factors, including genetic susceptibility, insulin resistance, hyperglycemia, abnormal lipid metabolism, vascular endothelial cell dysfunction, abnormal hormone levels, oxidative stress, and chronic inflammation.

[0004] Long-term disorders of carbohydrate, fat, and protein metabolism can cause multi-system damage, leading to chronic progressive lesions, functional decline, and failure of organs and tissues such as the eyes, kidneys, nerves, heart, and blood vessels. In severe cases or under stress, acute severe metabolic disorders can occur, which are the complications of diabetes. Chronic complications of diabetes can affect all vital organs throughout the body, and their pathogenesis is extremely complex and not yet fully understood. Currently, it is believed to be related to the interaction of multiple factors, including genetic susceptibility, insulin resistance, hyperglycemia, and oxidative stress. Oxidative stress caused by hyperglycemia is an important common mechanism, leading to tissue damage. In addition, factors directly or indirectly involved in the occurrence and development of various chronic complications include: abnormal levels of multiple hormones such as insulin, sex hormones, growth hormone, and catecholamines; abnormal lipid metabolism; changes in the endocrine and paracrine functions of adipocytes; inflammatory states; vascular endothelial cell dysfunction; and abnormal activity of the blood coagulation and fibrinolytic systems. Various complications can occur alone or in different combinations, simultaneously or sequentially. Most diabetic patients die from cardiovascular or cerebrovascular atherosclerosis or diabetic nephropathy. Compared to non-diabetic individuals, people with diabetes have a 1.5-2.7 times higher risk of death from all causes, a 1.5-4.5 times higher risk of cardiovascular disease mortality, a 10 times higher risk of blindness, and a 20 times higher risk of lower limb gangrene and amputation. Diabetic nephropathy is the first or second leading cause of death from kidney disease. Currently, the main chronic complications of diabetes include: diabetic vascular disease, kidney disease, heart disease, retinopathy, neuropathy, etc.

[0005] Modern medicine mainly treats diabetes with insulin secretagogues, alpha-glucosidase inhibitors, growth factor antagonists, and angiotensin-converting enzyme inhibitors, such as insulin, biguanides, and sulfonylureas. However, these drugs often have serious side effects and drug resistance. As the course of diabetes progresses, various chronic complications will appear to varying degrees, and once complications occur, they are difficult to control with Western medicine.

[0006] Traditional Chinese medicine classifies diabetes under the category of "Xiao Ke" syndrome, clinically categorized into Qi and Yin deficiency, Yin and Yang deficiency, and blood stasis and Qi stagnation types. Recent research indicates that treatment for diabetes is not solely based on lowering blood sugar, but rather on multiple aspects, including reducing non-enzymatic glycation of proteins and inhibiting aldose reductase. In particular, it utilizes holistic regulation, combining Qi-tonifying and Yin-nourishing with blood-activating and stasis-removing methods, demonstrating significant therapeutic advantages in improving diabetic complications.

[0007] The compound medicine involved in this invention includes four Chinese medicinal herbs: Coptis chinensis, Astragalus membranaceus, Panax notoginseng, and Rehmannia glutinosa.

[0008] Coptis chinensis has the effects of clearing heat and drying dampness, and is recorded in traditional medical literature as a commonly used Chinese medicine for treating diabetes. Berberine (BBR) is the main active ingredient of Coptis chinensis. Modern research reports that berberine has significant hypoglycemic and hypolipidemic effects. Furthermore, its therapeutic effect on diabetes is widely recognized and it is used clinically.

[0009] Astragalus is a highly regarded herb for replenishing Qi, possessing the functions of invigorating the spleen and replenishing Qi, nourishing blood, promoting Qi circulation, and strengthening the body's defensive Qi. Modern pharmacological studies have shown that components in astragalus, such as astragalus polysaccharides and total astragalus saponins, have certain therapeutic effects on diabetes, diabetic vascular disease, and diabetic retinopathy. Furthermore, astragalus also has immunomodulatory and antioxidant effects.

[0010] Panax notoginseng is a traditional Chinese medicine used for various types of bleeding, both internal and external, as well as traumatic injuries, swelling, and pain due to blood stasis. Raw Panax notoginseng promotes blood circulation, stops bleeding, reduces swelling, and relieves pain; it is used for hemoptysis, hematemesis, traumatic swelling and pain, and external bleeding. Processed Panax notoginseng nourishes and invigorates blood; it is used for blood loss and anemia. Total saponins of Panax notoginseng are the effective active components; modern research has proven that they have significant blood-activating and stasis-removing effects, and are used to improve cerebral ischemia, inhibit platelet aggregation, reduce blood viscosity, and have anti-thrombotic effects.

[0011] Rehmannia glutinosa is a key herb for nourishing Yin, possessing the effects of nourishing Yin and replenishing blood, as well as benefiting essence and marrow. Modern pharmacological studies have shown that Rehmannia glutinosa can regulate the body's immune and endocrine functions, and the oligosaccharides it contains can also lower blood sugar in diabetic animals. Summary of the Invention

[0012] This invention provides a drug formulated with Coptis chinensis, Astragalus membranaceus, Panax notoginseng and Rehmannia glutinosa, using modern pharmaceutical preparation methods, for the prevention and treatment of diabetes and its complications. The four-drug formula can both lower blood sugar and prevent and delay the occurrence and development of diabetic complications, achieving both symptomatic and root-cause treatment and synergistic effects.

[0013] Traditional Chinese medicine believes that the basic pathogenesis of diabetic complications is a gradual development from initial "deficiency of both Qi and Yin" to "deficiency of Yin in the liver and kidneys," ultimately leading to "deficiency of both Yin and Yang." This pathological process involves three important pathogenic factors: deficiency, blood stasis, and phlegm. Therefore, the treatment principle for diabetic complications should be to clear away toxins, nourish the liver and kidneys, and invigorate Qi, promote blood circulation, and unblock the meridians.

[0014] In this formula, Coptis chinensis is the chief herb. Coptis chinensis has the effects of clearing heat and drying dampness, purging fire and detoxifying, and is especially good at clearing the fire and toxins of the heart and liver. The *Shennong Bencao Jing* lists Coptis chinensis as a "superior herb," ​​recording: "It tastes bitter and cold, and treats heat, eye pain, canthal injury, and weeping. It brightens the eyes, relieves intestinal and abdominal pain, diarrhea, and swelling and pain in the vulva of women. Long-term use makes one forgetful." The *Yixue Zhongzhong Canxi Lu* records that Coptis chinensis "is good at entering the heart to clear heat. When the heat in the heart is cleared, the heat in the upper burner is also cleared, therefore it is good at treating meningitis, cerebral congestion, occasional dizziness, eye diseases with swelling and pain, and pterygium obscuring the eyes." The *Bielu* records that Coptis chinensis "stops thirst." Therefore, Coptis chinensis can regulate the spleen and stomach, clear the heart and purge the liver, and stop thirst and lower blood sugar—achieving three benefits at once, thus making it the chief herb.

[0015] In this formula, Astragalus and Panax notoginseng are the assistant herbs. Astragalus tonifies Qi and strengthens the exterior, promotes diuresis and eliminates toxins. The *Shennong Bencao Jing* lists Astragalus as a superior herb, stating that it is "sweet and slightly warm in nature, primarily treating carbuncles and chronic sores, draining pus and relieving pain, treating leprosy, dysentery, hemorrhoids, fistulas, tonifying deficiency, and treating various childhood illnesses." The *Yixue Zhongzhong Canxi Lu* records that Astragalus "can tonify Qi and also raise Qi, effectively treating Qi sinking in the chest… its Qi-tonifying effect is the best, hence it is considered the leader among tonics." Zhang Yuansu's *Yongyao Xinfa* states that it "tonifies the deficiencies of the five internal organs, drains Yin fire, removes deficiency heat, induces sweating when there is no sweat, and stops sweating when there is sweat." The *Chinese Pharmacopoeia* records Astragalus's effects as "tonifying Qi and raising Yang, strengthening the exterior and stopping sweating, promoting diuresis and reducing swelling, generating fluids and nourishing blood, promoting circulation and relieving pain, eliminating toxins and draining pus, and promoting wound healing and tissue regeneration." Panax notoginseng is mild in nature, sweet and slightly bitter in taste. It has the functions of resolving blood stasis and stopping bleeding, promoting blood circulation and relieving pain, and protecting the liver and improving eyesight. The medical record of integrating Chinese and Western medicine states that Panax notoginseng "is good at resolving blood stasis and stopping bleeding, and is an essential medicine for vomiting and nosebleeds." When combined with Astragalus membranaceus, Panax notoginseng invigorates Qi, promotes blood circulation, and unblocks the meridians, so that Qi is replenished, blood flows smoothly, the liver is nourished, and the eyes are clear.

[0016] The adjuvant herb in this formula is Rehmannia glutinosa. Rehmannia glutinosa is sweet and slightly bitter in taste, and cold in nature. Its functions include clearing heat and cooling the blood, nourishing yin and generating fluids, tonifying the liver and kidneys, and nourishing water and improving eyesight. The Compendium of Materia Medica records that Rehmannia glutinosa "fills bone marrow, promotes muscle growth, generates essence and blood, tonifies the five internal organs, treats internal injuries and deficiencies, unblocks blood vessels, benefits the ears and eyes, darkens hair, treats five types of fatigue and seven types of injury in men, and treats uterine bleeding, irregular menstruation, and various pregnancy and childbirth diseases in women." It can assist the principal and assistant herbs in treating both the root cause and the symptoms, achieving a proper balance of attack and tonification.

[0017] The four herbs, when used together, combine purgation and tonification to achieve the effects of clearing heat and purging turbidity, invigorating qi and blood, nourishing yin and improving eyesight.

[0018] Diabetes and its complications have a long course, and traditional Chinese medicine treatments typically involve large prescriptions, prolonged treatment periods, and poor patient adherence. This prescription, however, contains only four herbs, requiring a small dosage. Based on traditional Chinese medicine's understanding of the etiology and pathogenesis of diabetic complications, the selection of herbs is minimal yet precise, aligning with the characteristics of diabetic complications and treatment principles. Clinical trials have demonstrated that early application can prevent and control the occurrence and development of diabetic complications, consistent with the traditional Chinese medicine theory of preventive medicine. Therefore, it possesses practical advantages and significance.

[0019] On the one hand, this application provides a compound medicine containing Coptis chinensis, Astragalus membranaceus, Panax notoginseng and Rehmannia glutinosa.

[0020] Furthermore, the raw materials of the compound drug are Coptis chinensis, Astragalus membranaceus, Panax notoginseng, and Rehmannia glutinosa.

[0021] Furthermore, the weight ratio of Coptis chinensis, Astragalus membranaceus, Panax notoginseng and Rehmannia glutinosa is 3-8:10-20:1-5:5-15.

[0022] Furthermore, the weight ratio of Coptis chinensis, Astragalus membranaceus, Panax notoginseng, and Rehmannia glutinosa is 5:15:3:10.

[0023] Furthermore, the compound drug is prepared according to the following method:

[0024] (1) Coptis chinensis and Panax notoginseng were crushed into coarse powder;

[0025] (2) Add ethanol to the refluxed Coptis chinensis and Panax notoginseng powder, filter, and concentrate;

[0026] (3) Decoction of Astragalus membranaceus and Rehmannia glutinosa, filter the decoction and concentrate it;

[0027] (4) Combine the concentrated paste, dry it, and pulverize it.

[0028] Furthermore, the compound drug is in the form of tablets.

[0029] On the other hand, this application provides the use of the above-mentioned compound drug in the preparation of a drug for treating diabetes or diabetic complications.

[0030] Furthermore, the aforementioned diabetic complication is diabetic heart disease.

[0031] Furthermore, the aforementioned diabetic complication is diabetic nephropathy.

[0032] Furthermore, the aforementioned diabetic complication is diabetic retinopathy.

[0033] The medicinal materials used in this invention are commercially available.

[0034] The preferred, but not limited to, dosage form of the compound drug of the present invention is tablets. Other dosage forms, including but not limited to decoctions, pills, and capsules, may also be used. When different dosage forms are used, those skilled in the art can make routine adjustments to the preparation method.

[0035] Depending on the dosage form and the required properties of the preparation, those skilled in the art can select suitable excipients, including but not limited to disintegrants, lubricants, binders, etc., to prepare any commonly used oral dosage form, such as granules, pills, powders, tablets, capsules, etc., using conventional Chinese medicine preparation methods.

[0036] The symptoms and specific types of diabetic heart disease described in this application include, but are not limited to, diabetic coronary heart disease, microvascular heart disease, arrhythmia, and heart failure; the symptoms and specific types of diabetic nephropathy include, but are not limited to, proteinuria, edema, decreased glomerular filtration rate, renal insufficiency, and uremia; the symptoms and specific types of diabetic retinopathy include, but are not limited to, proliferative and non-proliferative retinopathy, basement membrane thickening, lens sclerosis, and abnormal proliferation of endothelial cells. Attached Figure Description

[0037] Figure 1 To investigate the effects of the drug on the pancreas of diabetic mice.

[0038] Figure 2 To investigate the effects of the test drug on the myocardial tissue of diabetic mice.

[0039] Figure 3 To investigate the effects of the test drug on the kidney tissue of diabetic mice.

[0040] Figure 4 To investigate the effects of the test drug on retinopathy in diabetic mice. Detailed Implementation

[0041] Example 1: Preparation of the drug of this application

[0042] Prescription: Coptis chinensis 313g, Astragalus membranaceus 939g, Panax notoginseng 188g, Rehmannia glutinosa 626g

[0043] Preparation method:

[0044] 1. Coptis chinensis and Panax notoginseng are ground into coarse powder.

[0045] 2. Take coarse powder of Coptis chinensis and coarse powder of Panax notoginseng, add 5 times the amount of 70% ethanol, heat and reflux twice, 2 hours each time, filter, combine the filtrates, recover the ethanol and concentrate to a thick paste with a relative density of 1.26-1.28 (50℃), and set aside for later use.

[0046] 3. Take Astragalus membranaceus and Rehmannia glutinosa, add 8 times the amount of water and decoct twice, 2 hours each time. Combine the decoctions, filter, and concentrate the filtrate to a clear paste with a relative density of 1.12-1.16 (50℃) (1 ml contains 1 g of raw herbs). Add ethanol to make the alcohol content reach 70%, let stand for 24 hours, filter, recover the ethanol from the filtrate and concentrate to a thick paste with a relative density of 1.26-1.28 (50℃).

[0047] 4. Combine the two thick pastes mentioned above, mix them well, and dry them under reduced pressure (0.08 MPa, 86°C) (yield approximately 440 g). Grind them into a fine powder, add 120 g of microcrystalline cellulose, 20 g of microcrystalline silica gel, and 20 g of sodium carboxymethyl starch, mix well, granulate with ethanol, dry, granulate, add 4.8 g of magnesium stearate, compress into 1000 tablets, and coat with a film to obtain the final product.

[0048] This embodiment is merely an illustrative example of a drug preparation method and does not constitute a limitation of the present invention.

[0049] Example 2: Effects of the drug of this application on type 2 diabetic mice

[0050] 1 Experimental Methods

[0051] 1.1 Modeling and Drug Administration

[0052] C57 mice, after one week of acclimatization, were randomly divided into a control group and a model group. The control group was fed a conventional diet, while the model group was fed a high-fat, high-sugar diet (KK diet). After four weeks of feeding, the animals in the model group were fasted for 12 hours but allowed free access to water, and then received a single intraperitoneal injection of streptozotocin (STZ) 100 mg / kg; the control group received only an equal volume of citrate-sodium citrate buffer. One week later, a blood glucose level greater than 12.0 mmol / L was measured by blood sample taken from the tail tip to indicate successful modeling. The successfully modeled mice were then randomly divided into a model group, a metformin group (220 mg / kg), a high-dose drug group (1.32 g / kg), and a low-dose drug group (0.66 g / kg) according to the principle of balanced blood glucose and body weight. The drugs were administered for a total of 12 weeks. During this period, all animals except the control group continued to be fed a high-fat, high-sugar diet.

[0053] 1.2 Blood glucose testing

[0054] Blood was collected from the tail vein of the animals every two weeks, and random blood glucose levels were measured in each group of mice using a blood glucose meter.

[0055] 1.3 Oral glucose tolerance test

[0056] Mice were fasted overnight for 12 hours and then administered glucose solution (2 g / kg) by gavage. Blood was collected from the tail vein, and the blood glucose concentration was measured at 0 min, 30 min, 60 min, and 120 min after gavage. Glucose tolerance curves were plotted, and the area under the curve (AUC) of the oral glucose tolerance test was calculated using the approximate trapezoidal method.

[0057] 1.4 Sample collection and pathological testing

[0058] Mice were anesthetized by intraperitoneal injection of chloral hydrate 400 mg / kg. Blood was collected from the retrobulbar vein, serum was separated and stored at -80℃. Pancreas, heart, kidney, and eyeballs were taken, rinsed with ice-cold saline, blotted dry with filter paper, fixed with formaldehyde solution, and subjected to pathological examination.

[0059] 1.5 Biochemical index detection

[0060] The levels of creatine kinase (CK), blood urea nitrogen (BUN), and creatinine (Cre) in the serum of mice in each group were analyzed using a fully automated biochemical analyzer.

[0061] 1.6 Detection of serum insulin levels

[0062] The ELISA method is used to detect the level of insulin in serum.

[0063] 2 Results

[0064] 2.1 Effects on blood glucose in diabetic mice

[0065] Compared with the control group, the blood glucose levels of mice in the model group were significantly elevated from week 0 to week 12. Compared with the model group, the blood glucose levels of mice in the metformin group were significantly lower from week 2 to week 12 after administration, and the differences were statistically significant. The blood glucose levels of mice in the high-dose group were significantly lower from week 2 to week 12 after administration, and the differences were statistically significant. The blood glucose levels of mice in the low-dose group were lower than those in the model group to some extent. The results are shown in Table 1.

[0066] Table 1. Effects of the test drug on blood glucose in diabetic mice ( Unit: mmol / L

[0067]

[0068] Note: Compared with the model group, *p < 0.05, **p < 0.01, ***p < 0.001, and the same applies to all tables below.

[0069] Continued from Table 1: Effects of the test drug on blood glucose in diabetic mice ( Unit: mmol / L

[0070]

[0071] 2.2 Effects on glucose tolerance in diabetic mice

[0072] Compared with the control group, the blood glucose levels of mice in the model group were significantly increased at 0 min, 30 min, 60 min, and 120 min after glucose gavage. Compared with the model group, the blood glucose levels of the metformin group and the high-dose drug group were significantly decreased from 0 to 120 min after glucose gavage, while the blood glucose level of the low-dose drug group was significantly decreased from 60 to 120 min. Compared with the control group, the AUC of the model group was significantly increased; compared with the model group, the AUC of mice in the metformin group and the high- and low-dose drug groups was significantly decreased. The results are shown in Table 2.

[0073] Table 2 Effects on oral glucose tolerance in mice ( n=10)

[0074]

[0075] 2.3 Effects on serum CK, BUN and Cre levels in diabetic mice

[0076] Compared with the control group, the serum levels of CK, BUN, and Cre in the model group were significantly increased. Compared with the model group, the serum levels of CK, BUN, and Cre in the high-dose drug group were significantly decreased. The serum CK level in the low-dose drug group was decreased. The results are shown in Table 3.

[0077] Table 3. Effects of the test drugs on serum CK, BUN, and Cre levels in diabetic mice.

[0078]

[0079] 2.4 Effects on the pancreas of diabetic mice

[0080] In the control group, large, round, or oval islet tissues were scattered throughout the pancreas, without shrinkage or atrophy, and no vacuolar degeneration or atrophy of the pancreatic exocrine portion was observed. In the model group, a significantly reduced number of smaller islet tissues were scattered throughout the pancreas. In the metformin group, larger, rounder islet tissues were scattered throughout the pancreas, with a reduced number and greater volume and number than in the model group. In the high-dose group, larger and more numerous islet tissues were scattered throughout the pancreas, with a higher number of islets than in the model and metformin groups. In the low-dose group, larger, rounder islet tissues were scattered throughout the pancreas, but fewer in number, with a greater volume and number than in the model group. See [link to relevant documentation]. Figure 1 .

[0081] 2.5 Effects on myocardial tissue of diabetic mice

[0082] No obvious abnormal morphological changes were observed in the heart tissue of mice in the control group; the cardiomyocytes were neatly and densely arranged. In the model group, the myocardial tissue showed myocardial loosening, edema, and uneven staining in the endocardium or a large portion of the myocardium, exhibiting typical diabetic myocardial degeneration. In the metformin group, the myocardial tissue showed minor myocardial loosening and edema in the endocardium, with a smaller affected area and a milder overall lesion severity than the model group. In the high-dose group, the myocardial tissue showed only mild loosening and edema, with virtually no obvious damaging changes. In the low-dose group, the myocardial tissue showed partial myocardial loosening, edema, and uneven staining, with a degree of reduction compared to the model group. (See...) Figure 2 .

[0083] 2.6 Effects on kidney tissue of diabetic mice

[0084] No obvious abnormal morphological changes were observed in the kidney tissue of mice in the control group. In the model group, glomerular dilation, thickening of the glomerular basement membrane, widening of the interstitium, increased glomerular mesangial matrix, and tubular degeneration were observed in the kidney tissue, exhibiting typical manifestations of diabetic nephropathy. In the metformin group and the high- and low-dose groups, the degree of glomerular dilation and tubular degeneration was reduced, and the overall condition was milder than in the model group. (See...) Figure 3 .

[0085] 2.7 Effects on retinopathy in diabetic mice

[0086] HE staining showed no abnormalities in the cornea, lens, vitreous body, sclera, and retina of the control group mice; the retinal tissue structure was intact, with regular cell morphology and clear staining. Ganglion cells were abundant, densely and continuously arranged. The nuclear lamina showed a dense arrangement of cells, and the outer nuclear lamina also showed a large number of cells, arranged densely. No vacuolar degeneration was observed in the pigment epithelium.

[0087] Compared with the control group, the model group mice showed no abnormalities in the cornea, vitreous body, and sclera, but exhibited lens sclerosis with uneven texture and increased hardness, which is related to fibrous proliferation induced by high glucose and hypoxia. The vascular component within the inner limiting membrane of the retina increased; ganglion cell layer cells swelled, showed vacuolar degeneration, decreased ganglion number, elongated intercellular spacing, and sparse distribution; the inner plexiform layer thinned; the nuclear lamina decreased in number and showed vacuolar degeneration; the outer plexiform layer thinned; the outer nuclear lamina decreased in number and showed vacuolar degeneration; vacuolar degeneration appeared in the pigment epithelium cells; and the overall retinal thickness thinned, which is related to a decrease in the number of surviving retinal cells and a reduction in components after structural damage.

[0088] In the metformin group, no abnormalities were observed in the cornea, vitreous body, or sclera, but the lens texture was uneven. Compared with the model group, no significant increase in vascular components was observed in the internal limiting membrane of the retina; ganglion cell layer cells were swollen, the degree of vacuolar degeneration was reduced, and the number of ganglia increased; the inner plexiform layer was thickened; vacuolar degeneration was rare in the nuclear layer cells; the outer plexiform layer was thickened; vacuolar degeneration was rare in the outer nuclear layer cells; vacuolar degeneration was rare in the pigment epithelium cells; the overall thickness of the retina increased, and the number of surviving ganglion cells increased.

[0089] In mice in the high-dose drug group, no abnormalities were observed in the lens, vitreous body, or sclera. Compared to the model group, the thickness of each retinal layer increased, cell morphology was generally regular, and staining was clear. The number of ganglion cells increased, with dense and continuous cell arrangement and reduced intercellular spacing. Cells in the nuclear lamina were densely packed, with a large number of cells and few instances of vacuolar degeneration; cells in the outer nuclear lamina were also numerous and densely packed, with few instances of vacuolar degeneration. No vacuolar degeneration was observed in the pigment epithelium. This effectively increased retinal thickness, increased the number of surviving ganglion cells, and reduced the degree of retinal damage.

[0090] In mice in the low-dose drug group, no abnormalities were observed in the cornea, vitreous body, or sclera, but the lens texture was uneven. Compared with the model group, the vascular component in the internal limiting membrane of the retina was significantly increased; ganglion cell layer cells were swollen, vacuolar degeneration was observed, and the number of ganglia was reduced; the inner plexiform layer was thinned; vacuolar degeneration was observed in the nuclear lamina cells; the outer plexiform layer was thinned; the number of outer nuclear lamina cells was reduced; the overall thickness of the retina was increased, and the number of surviving ganglion cells was increased, which has a certain protective effect on the retina. See Figure 4 .

[0091] As can be seen from the above experiments, the drug involved in this invention has good preventive and therapeutic effects on diabetes and various diabetic complications such as diabetic heart disease, diabetic nephropathy, and diabetic retinopathy. Compared with metformin, it has certain advantages and characteristics and can be used as a drug for the treatment and prevention of diabetes and its complications.

Claims

1. The use of a compound medicine for treating diabetes or diabetic complications in the preparation of a medicine for treating diabetic retinopathy, said compound medicine being made from Coptis chinensis, Astragalus membranaceus, Panax notoginseng, and Rehmannia glutinosa in a weight ratio of 5:15:3:10; said compound medicine being prepared according to the following method: (1) Coptis chinensis and Panax notoginseng were crushed into coarse powder; (2) Ethanol was heated and refluxed to extract the coarse powder of Coptis chinensis and Panax notoginseng, then filtered and concentrated. (3) Decoction of Astragalus membranaceus and Rehmannia glutinosa, filter the decoction and concentrate it; (4) Combine the concentrated paste, dry it, and pulverize it.

2. The application according to claim 1, wherein the compound drug is a tablet.

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