Traditional chinese medicine composition for treating nonproliferative diabetic retinopathy, its preparation method and application

Abstract

This application relates to the field of traditional Chinese medicine preparation technology, and in particular to a traditional Chinese medicine composition for treating non-proliferative diabetic retinopathy, its preparation method, and its application. The composition includes Astragalus complanatus, Tribulus terrestris, Eriocaulon buergerianum, Equisetum hyemale, Salvia miltiorrhiza, Paeonia lactiflora, Polygonum cuspidatum, Cynanchum paniculatum, Ligusticum chuanxiong, and Pueraria lobata. This composition improves retinal microvascular lesions through a synergistic effect of benefiting the liver and improving vision, promoting blood circulation and removing blood stasis, and clearing the meridians and relieving pain. The preparation method involves water extraction, concentration, and drying to obtain a dry extract powder, which can then be formulated into granules, tablets, or capsules. Clinically, it is suitable for patients with liver and kidney deficiency and meridian obstruction syndrome, and can inhibit VEGF expression, repair retinal barrier function, and promote the absorption of microaneurysms and exudates.

Description

(19) State Intellectual Property Office (12) Invention Patent Application (10) Application Publication Number (43) Application Publication Date (21) Application Number 202511995224.5 (22) Application Date 2025.12.26 (71) Applicant Heilongjiang Jiren Pharmaceutical Co., Ltd. Address 150025 No. 1, Yuandong Street, Limin Development Zone, Harbin, Heilongjiang Province (72) Inventors Lu Fang, Han Bing, Fu Yingnan, Liu Liying, Kang Ning, Han Xunan (74) Patent Agency Beijing Zhongda Dequan Intellectual Property Agency Co., Ltd. 11570 Patent Attorney Yang Yang (51) Int.Cl. A61K 36 / 88 (2006.01) A61K 36 / 481 (2006.01) A61K 36 / 185 (2006.01) A61K 9 / 16 (2006.01) A61K 9 / 20(2006.01) A61K 9 / 48(2006.01) A61K 47 / 38(2006.01) A61K 47 / 32(2006.01) A61P 3 / 10(2006.01) A61P 9 / 10(2006.01) (54) Invention Title: A Traditional Chinese Medicine Composition for Treating Non-Proliferative Diabetic Retinopathy, Its Preparation Method and Application (57) Abstract: This application relates to the field of traditional Chinese medicine preparation technology, and in particular to a traditional Chinese medicine composition for treating non-proliferative diabetic retinopathy, its preparation method and application, which includes Astragalus complanatus, Tribulus terrestris, Eriocaulon buergerianum, Equisetum hyemale, Salvia miltiorrhiza, Paeonia lactiflora, Polygonum cuspidatum, Cynanchum paniculatum, Ligusticum chuanxiong and Pueraria lobata. This composition improves fundus microvascular lesions through multiple synergistic effects such as benefiting the liver and improving vision, promoting blood circulation and removing blood stasis, and relieving pain. The preparation method involves water extraction, concentration, and drying to obtain a dry extract powder, which is then formulated into granules, tablets, or capsules. Clinically, it is suitable for patients with liver and kidney deficiency and blood stasis syndrome. It can inhibit VEGF expression, repair retinal barrier function, and promote the absorption of microaneurysms and exudates. Claims: 1 page; Specification: 25 pages; Drawings: 5 pages. CN 122537462 A 2026.08.11 CN 1 22 53 74 62 A 1. A traditional Chinese medicine composition for treating non-proliferative diabetic retinopathy, characterized in that the traditional Chinese medicine composition comprises Astragalus complanatus, Tribulus terrestris, Eriocaulon buergerianum, Equisetum hyemale, Salvia miltiorrhiza, Paeonia lactiflora, Polygonum cuspidatum, Cynanchum paniculatum, Ligusticum chuanxiong, and Pueraria lobata. 2. The traditional Chinese medicine composition according to claim 1, characterized in that, by weight parts, it comprises 2-10 parts of Astragalus complanatus, 2-10 parts of Tribulus terrestris, 2-10 parts of Eriocaulon buergerianum, 1-5 parts of Equisetum hyemale, 3-15 parts of Salvia miltiorrhiza, 3-15 parts of Paeonia lactiflora, 2-10 parts of Polygonum cuspidatum, 1-10 parts of Cynanchum paniculatum, 2-10 parts of Ligusticum chuanxiong, and 1-5 parts of Pueraria lobata. 3. The traditional Chinese medicine composition according to claim 2, characterized in that, by weight parts, the traditional Chinese medicine composition comprises...The formula consists of 4.5 parts of Astragalus complanatus, 4.5 parts of Tribulus terrestris, 4.5 parts of Eriocaulon buergerianum, 2.5 parts of Equisetum hyemale, 6.5 parts of Salvia miltiorrhiza, 6.5 parts of Paeonia lactiflora, 4.5 parts of Polygonum cuspidatum, 3 parts of Cynanchum paniculatum, 4.5 parts of Ligusticum chuanxiong, and 2 parts of Pueraria lobata. 4. A method for preparing a traditional Chinese medicine composition as described in any one of claims 1 to 3, characterized in that it comprises: weighing the following slices according to the prescription ratio: Astragalus complanatus, Tribulus terrestris, Eriocaulon buergerianum, Equisetum hyemale, Salvia miltiorrhiza, Paeonia lactiflora, Polygonum cuspidatum, Cynanchum paniculatum, Ligusticum chuanxiong, and Pueraria lobata; adding 10 times the amount of water and decocting at 95-100°C for 60 minutes; filtering; adding 8 times the amount of water to the residue and decocting at 90-95°C for 30 minutes; filtering; combining the two filtrates; concentrating under reduced pressure to a relative density of 1.20±0.05 (60°C); drying the concentrate under reduced pressure at 50-70°C; pulverizing the concentrate through a 60-100 mesh sieve to obtain a dry extract powder; mixing the dry extract powder with pharmaceutically acceptable excipients; and preparing granules using dry granulation or wet granulation processes, or adding microcrystalline cellulose and magnesium stearate to compress into tablets, or filling into empty capsule shells to prepare capsules. 5. The preparation method according to claim 4, characterized in that the vacuum concentration process uses a double-effect concentrator, and the vacuum degree is maintained at -0.08 to -0.09 MPa; the vacuum drying process uses a vacuum drying oven, and the vacuum degree is not lower than -0.09 MPa, with the drying endpoint determined by a moisture analyzer showing that the moisture content of the dry extract powder does not exceed 8.0%. 6. The preparation method according to claim 4, characterized in that, when preparing granules, the dry extract powder is mixed with dextrin and sucrose powder at a mass ratio of 1:1:1, and an 8% polyvinylpyrrolidone ethanol solution is added as a binder. The mixture is stirred to form a soft mass, passed through a 16-mesh sieve to form wet granules, dried at 60°C in a forced-air drying process for 2 hours, and then packaged into granules containing 6g of raw medicinal material per bag. 7. The preparation method according to claim 4, characterized in that, when preparing tablets, the dry extract powder and microcrystalline cellulose are mixed at a mass ratio of 1:0.8, 2% sodium carboxymethyl starch is added as a disintegrant, and 0.5% magnesium stearate is added as a lubricant. After mixing evenly, the mixture is compressed into tablets, each containing 1.5g of raw medicinal material. 8. The preparation method according to claim 4, characterized in that, when preparing capsules, the dry extract powder is directly filled into capsules. 9. The application of the traditional Chinese medicine composition according to any one of claims 1 to 3 in the preparation of a drug for treating non-proliferative diabetic retinopathy, characterized in that the non-proliferative diabetic retinopathy is a syndrome of liver and kidney deficiency and blood stasis, clinically manifested as blurred vision, dry eyes, dizziness and tinnitus, soreness and weakness of the waist and knees, numbness of the limbs, constipation, dark red tongue with little coating or ecchymosis, and a thready and hesitant pulse. 10. The application according to claim 9, characterized in that the traditional Chinese medicine composition is an oral preparation. Claims 1 / 1 page 2 CN 122537462 A A traditional Chinese medicine composition for treating non-proliferative diabetic retinopathy, its preparation method and applicationTechnical Field

[0001] This invention belongs to the field of traditional Chinese medicine technology, specifically a traditional Chinese medicine composition for treating non-proliferative diabetic retinopathy and its preparation method and application. Background Art

[0002] Diabetic retinopathy (hereinafter referred to as "DR") is a retinal complication caused by diabetes, mainly manifested as damage to retinal microvessels, which may be accompanied by retinal neuropathy. It is a progressive blinding eye disease. DR is divided into non-proliferative diabetic retinopathy (NPDR) and proliferative diabetic retinopathy (PDR), both of which can lead to diabetic macular edema (DME).

[0003] The epidemiological distribution of DR varies significantly globally, mainly related to the level of economic development, accessibility of medical resources, level of diabetes management, and population risk characteristics in different regions. Currently, about 25% of diabetic patients worldwide have DR, of which 6% have developed vision-threatening lesions. It is worth noting that the disease burden of DR is gradually shifting from high-income countries or regions to low- and middle-income countries or regions.

[0004] Data from my country show that the prevalence of DR varies significantly by region. A national survey showed that the overall prevalence of diabetes mellitus (DR) was 16.3%, of which DR threatening vision accounted for 3.2%; while a meta-analysis reported that the overall prevalence of DR was 12.5%, with DR threatening vision accounting for 4.0%. The main risk factors for DR patients in rural areas include hypertension, long duration of diabetes, and poor glycemic control.

[0005] India also shows a significant urban-rural difference in the prevalence of DR. Inter-country comparisons found that the prevalence of DR in countries with high human development index was 22.6%, lower than the 63.6% in countries with low human development index. The prevalence in the Middle East and North Africa is as high as 34.6%, with a high proportion of severe cases, making prevention and control a serious challenge. It is estimated that by 2030, the prevalence of DR in high-income countries will remain at 10.8% to 18.0%, while it may rise sharply to 20.6% to 47.2% in low- and middle-income countries. In addition, it is estimated that by 2045, diabetes will affect 783 million people aged 20 to 79 worldwide, accounting for 12.2% of the global adult population. With increasing life expectancy and rising diabetes prevalence, the prevalence of diabetic retinopathy (DR) will also increase.

[0006] In terms of treatment, anti-VEGF drugs are currently the core of drug treatment for diabetic retinopathy (DR). They inhibit pathological angiogenesis and reduce vascular leakage by blocking the activity of vascular endothelial growth factor (VEGF). Commonly used drugs include monoclonal antibodies (such as ranibizumab and bevacizumab) and fusion proteins (such as aflibercept and conbercept), both of which need to be administered via intravitreal injection. It is worth noting that anti-VEGF treatment can improve vision in diabetic macular edema (DME) and proliferative lesions by more than 60%, but about 30% of patients are resistant to treatment. Its limitation is that repeated treatment is required.Injection (every 4-8 weeks) may induce increased intraocular pressure or vitreous hemorrhage. Glucocorticoids are mainly used for refractory macular edema that is unresponsive to anti-VEGF therapy. They work by inhibiting inflammatory factors (such as IL-6 and TNF-α) and repairing the blood-retinal barrier (i.e., the selective filtration structure that maintains the stability of the retinal microenvironment). Long-acting implantable formulations, such as dexamethasone intravitreal implants, can maintain efficacy for 4-6 months and significantly reduce the frequency of injections. However, glucocorticoids may induce cataract progression and increased intraocular pressure, so they are often used as a second-line treatment.

[0007] Combination therapy and adjuvant therapy are gradually becoming a new trend. For example, traditional Chinese medicines such as Compound Danshen Dripping Pills improve retinal microcirculation by promoting blood circulation and removing blood stasis. When used in combination with anti-VEGF therapy, they can increase the treatment efficacy of non-proliferative DR by 84.4%. Aldose reductase inhibitors (such as epalrestat) alleviate oxidative stress by reducing sorbitol accumulation and are suitable for patients with early microaneurysms.

[0008] Traditional Chinese medicine (TCM) considers diabetic retinopathy (DR) to fall under the categories of "Xiao Ke Mu Bing" (wasting and thirsting eye disease) and "Xiao Ke Nei Zhang" (wasting and thirsting internal cataracts). DDR patients can preserve and improve visual function and slow disease progression through systemic and local ocular treatments. Existing research shows that TCM treatment has certain effects or unique advantages on DDR, especially non-proliferative diabetic retinopathy and diabetic macular edema. It also has potential research value for the efficacy against proliferative diabetic retinopathy. A well-designed clinical research study can promote the development of TCM treatment for DDR. How to discover new TCM drugs with potential clinical value for DDR based on TCM theory and clinical efficacy, and how to verify clinical efficacy with reliable data, are urgent scientific problems to be solved in the current research and development of new TCM drugs related to DDR.

[0009] The purpose of this invention is to provide a TCM composition for treating non-proliferative diabetic retinopathy, its preparation method, and its application.

[0010] To achieve the above-mentioned objectives of the present invention, the following technical solution is adopted:

[0011] In a first aspect, the present invention provides a traditional Chinese medicine composition for treating non-proliferative diabetic retinopathy, the traditional Chinese medicine composition comprising Astragalus complanatus, Tribulus terrestris, Eriocaulon buergerianum, Equisetum hyemale, Salvia miltiorrhiza, Paeonia lactiflora, Polygonum cuspidatum, Cynanchum paniculatum, Ligusticum chuanxiong, and Pueraria lobata.

[0012] Further, in a preferred embodiment of the present invention, by weight, Astragalus complanatus comprises 2-10 parts, Tribulus terrestris comprises 2-10 parts, Eriocaulon buergerianum comprises 2-10 parts, Equisetum hyemale comprises 1-5 parts, Salvia miltiorrhiza comprises 3-15 parts, Paeonia lactiflora comprises 3-15 parts, Polygonum cuspidatum comprises 2-10 parts, Cynanchum paniculatum comprises 1-10 parts, Ligusticum chuanxiong comprises 2-10 parts, and Pueraria lobata comprises 1-5 parts.

[0013] Further, in a preferred embodiment of the present invention, the traditional Chinese medicine composition, by weight, comprises 4.5 parts of Astragalus complanatus, 4.5 parts of Tribulus terrestris, 4.5 parts of Eriocaulon buergerianum, 2.5 parts of Equisetum hyemale, 6.5 parts of Salvia miltiorrhiza, 6.5 parts of Paeonia lactiflora, 4.5 parts of Polygonum cuspidatum, and 3 parts of Cynanchum paniculatum.The composition consists of 4.5 parts of Ligusticum chuanxiong and 2 parts of Pueraria lobata.

[0014] Further, in a preferred embodiment of the present invention, the raw materials in the traditional Chinese medicine composition are mixed in the form of decoction pieces and then subjected to water extraction. The extract is concentrated and dried to make a dry powder. The water content of the dry powder is controlled below 8%, and the total solid yield is not less than 16%.

[0015] Further, in a preferred embodiment of the present invention, Astragalus complanatus and Tribulus terrestris are the principal herbs in the traditional Chinese medicine composition. Astragalus complanatus tonifies the kidney and strengthens essence, nourishes the liver and improves eyesight, and replenishes essence and blood to nourish the eye network; Tribulus terrestris soothes the liver qi and removes blood stasis and unblocks the network. One tonifies and the other disperses, regulating the liver and kidneys, tonifying without stagnation and dispersing without depletion, which is the basis for tonifying the liver and kidneys and strengthening the foundation for improving eyesight. Eriocaulon buergerianum and Equisetum hyemale are the assistant herbs. Eriocaulon buergerianum disperses wind-heat in the liver meridian, with a clearing and dispersing effect, while Equisetum hyemale disperses wind and clears away nebula, emphasizing unblocking and promoting circulation. Both enter the liver meridian, assisting in enhancing the principal herbs' ability to clear nebula, heat, and improve vision and unblock the meridians. Salvia miltiorrhiza, Paeonia lactiflora, Polygonum cuspidatum, and Cynanchum paniculatum are the adjuvant herbs. Salvia miltiorrhiza invigorates blood, removes blood stasis, unblocks the meridians, and relieves pain. Paeonia lactiflora clears heat, cools the blood, disperses blood stasis, and relieves pain. Together, they delay the effect of "mutual binding of blood stasis and heat." Polygonum cuspidatum is cold in nature and is good at clearing heat toxins with cold. Cynanchum paniculatum is warm in nature and is good at dispersing wind evil with warmth. The combination of cold and warm herbs regulates the complex pathogenesis of "damp-heat and blood stasis toxins." Ligusticum chuanxiong and Pueraria lobata are the guiding herbs. Ligusticum chuanxiong is pungent, dispersing, and warming, and is good at penetrating and can guide the herbs upward to the head and eyes. Pueraria lobata is "sweet, cool, and penetrating," clearing the meridians, raising yang qi, generating fluids, and quenching thirst. It can neutralize the warm and drying properties of the herbs in the formula and prevent damage to yin and promotion of fire. The two complement each other through their pungent-warm and sweet-cool properties, achieving the effects of "guiding the medicine upwards" and "unblocking the channels and reaching the surface," thus promoting the efficacy of the medicine to reach the eyes. The whole formula nourishes the liver and kidneys to treat the root cause, while resolving blood stasis, unblocking the channels, and improving eyesight to treat the symptoms. It replenishes deficiency and drains excess, working together to disperse blood stasis, unblock the channels, improve eyesight, and remove corneal opacity.

[0016] In a second aspect, the present invention provides a method for preparing a traditional Chinese medicine composition for treating non-proliferative diabetic retinopathy, comprising: weighing the following slices according to the prescription ratio: Astragalus complanatus, Tribulus terrestris, Eriocaulon buergerianum, Equisetum hyemale, Salvia miltiorrhiza, Paeonia lactiflora, Polygonum cuspidatum, Cynanchum paniculatum, Ligusticum chuanxiong, and Pueraria lobata; adding 10 times the amount of water and decocting for 60 minutes; filtering; adding 8 times the amount of water to the residue and decocting for 30 minutes; filtering; combining the two filtrates; concentrating under reduced pressure to a relative density of 1.20±0.05 (60℃); drying the concentrate under reduced pressure at 50-70℃; pulverizing the concentrate through a 60-100 mesh sieve to obtain a dry extract powder; mixing the dry extract powder with pharmaceutically acceptable excipients; and preparing granules by dry granulation or wet granulation, or adding microcrystalline cellulose and magnesium stearate to compress into tablets, or filling into empty capsule shells to prepare capsules.

[0017] Further, in a preferred embodiment of the present invention, the first decoction temperature in the preparation method is controlled at 95-100℃, the second decoction temperature is controlled at 90-95℃, the concentration process uses a double-effect concentrator and the vacuum degree is maintained at -0.08 to -0.09 MPa, the drying process uses a vacuum drying oven and the vacuum degree is not lower than -0.09 MPa, and the drying endpoint is measured by a moisture analyzer.The moisture content of the dry extract powder shall not exceed 8.0%.

[0018] Further, in a preferred embodiment of the present invention, the dry extract powder is mixed with dextrin and sucrose powder at a mass ratio of 1:1:1, and 8% polyvinylpyrrolidone ethanol solution is added as a binder. The mixture is stirred to form a soft material, which is then passed through a 16-mesh sieve to form wet granules. The granules are dried at 60°C for 2 hours, sized, and then packaged into granules containing 6g of raw medicinal material per bag; or the dry extract powder is mixed with microcrystalline cellulose at a mass ratio of 1:0.8, and 2% sodium carboxymethyl starch is added as a disintegrant and 0.5% magnesium stearate is added as a lubricant. After mixing evenly, the mixture is compressed into tablets, each containing 1.5g of raw medicinal material; or the dry extract powder is directly filled into capsules, each containing 0.75g of raw medicinal material.

[0019] In a third aspect, the present invention provides the application of the aforementioned traditional Chinese medicine composition in the preparation of a drug for treating non-proliferative diabetic retinopathy, wherein the non-proliferative diabetic retinopathy is a syndrome of liver and kidney deficiency and blood stasis, clinically manifested as blurred vision, dry eyes, dizziness and tinnitus, soreness and weakness of the waist and knees, numbness of the limbs, constipation, dark red tongue with little coating or ecchymosis, and thready and hesitant pulse.

[0020] Further, in a preferred embodiment of the present invention, the traditional Chinese medicine composition achieves absorption or dissipation of fundus microaneurysms, hemorrhages, exudates and non-perfusion areas in non-proliferative diabetic retinopathy by inhibiting the expression of vascular endothelial growth factor (VEGF) in serum, upregulating the levels of retinal microvascular tight junction proteins Occludin and Claudin-5, reducing the ratio of endothelial cells to pericytes, increasing the positive density of retinal ganglion cells Brn3a, and improving the total thickness of the retina and the morphology of microvessels. Figure Descriptions

[0021] Figure 1: Pathological morphology of the retina of rats in each group after 7 weeks of drug administration (400×, Scale Bar: 40µm, number of animals in each group as in Table 16)

[0022] Figure 2: Pathological morphology of the retina of rats in each group after 12 weeks of drug administration (400×, Scale Bar: 40µm, number of animals in each group as in Table 17)

[0023] Figure 3: Pathological morphology of the microvessels of the retina of rats in each group after 7 weeks of drug administration (400×, Scale Bar: 40µm, yellow arrow: endothelial cells; red arrow: pericytes, number of animals in each group as in Table 18)

[0024] Figure 4: Pathological morphology of the microvessels of the retina of rats in each group after 12 weeks of drug administration (400×, Scale Bar: 40µm, yellow arrow: endothelial cells; red arrow: pericytes, number of animals in each group as in Table 19)

[0025] Figure 5: Positive expression of Occludin in the microvessels of the retina of rats in each group after 7 weeks of drug administration (400×, Scale Bar: 40µm, yellow arrow: endothelial cells; red arrow: pericytes, number of animals in each group as in Table 19) Bar: 40 µm, number of animals in each group as in Table 20)

[0026] Figure 6: Occludin positive expression in retinal microvessels of rats in each group after 12 weeks of drug administration (400×, Scale Bar: 40 μm, number of animals in each group as in Table 21)

[0027] Figure 7: Claudin-5 positive expression in the retinal microvessels of rats in each group after 7 weeks of drug administration (400, Scale Bar: 40µm, number of animals in each group as in Table 20)

[0028] Figure 8: Claudin-5 positive expression in the retinal microvessels of rats in each group after 12 weeks of drug administration (400, Scale Bar: 40µm, number of animals in each group as in Table 21) Instructions 3 / 25 Page 5 CN 122537462 A

[0029] Figure 9: Brn3a positive cells in the retina of rats in each group after 7 weeks of drug administration (400, Scale Bar: 40µm, yellow arrow: Brn3a positive cells, number of animals in each group as in Table 22)

[0030] Figure 10: Brn3a positive cells in the retina of rats in each group after 12 weeks of drug administration (400, Scale Bar: 40µm, yellow arrow: Brn3a positive cells, number of animals in each group as in Table 23)

[0031] Beneficial Effects of the Invention

[0032] The pharmaceutical composition of the present invention is a pure traditional Chinese medicine preparation, which has the effects of dispersing blood stasis and unblocking collaterals, improving eyesight and clearing away pterygium. It is used for non-proliferative diabetic retinopathy caused by type 2 diabetes mellitus, which is caused by deficiency of liver and kidney and obstruction of collaterals, resulting in blurred vision, dry eyes, dizziness, tinnitus, soreness and weakness of waist and knees, numbness of limbs, constipation, dark red tongue with little coating or ecchymosis, and thready and hesitant pulse. Detailed Embodiments

[0033] The present invention relates to a traditional Chinese medicine composition for treating non-proliferative diabetic retinopathy and its preparation method and application, which belongs to the field of traditional Chinese medicine compound preparation technology. According to Article 26, Paragraph 3 of the Patent Law of the People's Republic of China, the technical solution of the present invention will be clearly and completely described below so that those skilled in the art can realize the present invention.

[0034] The traditional Chinese medicine composition provided by the present invention is composed of ten traditional Chinese medicinal materials: Astragalus complanatus, Tribulus terrestris, Eriocaulon buergerianum, Equisetum hyemale, Salvia miltiorrhiza, Paeonia lactiflora, Polygonum cuspidatum, Cynanchum paniculatum, Ligusticum chuanxiong and Pueraria lobata. All the above-mentioned medicinal materials were used in the form of processed medicinal slices as specified in the relevant section of Part I of the 2020 edition of the Pharmacopoeia of the People's Republic of China. Their sources were clearly identified, the processing was standardized, and they were free from quality problems such as mold, insect infestation, and excessive impurities. In the specific implementation process, each raw material medicinal slice was first accurately weighed according to the prescription ratio. In a preferred embodiment, the proportions used by weight were: Astragalus complanatus 4.5 parts, Tribulus terrestris 4.5 parts, Eriocaulon buergerianum 4.5 parts, Equisetum hyemale 2.5 parts, Salvia miltiorrhiza 6.5 parts, Paeonia lactiflora 6.5 parts, Polygonum cuspidatum 4.5 parts, Cynanchum paniculatum 3 parts, Ligusticum chuanxiong 4.5 parts, and Pueraria lobata 2 parts. The weighing process was completed using a calibrated electronic balance with an accuracy of not less than 0.1g to ensure the accuracy of the proportions of each component.

[0035] After weighing, all the medicinal slices were placed into a stainless steel extraction tank, and drinking water equivalent to 10 times the total weight of the medicinal materials was added. The decoction temperature was controlled within the range of 95-100℃, and the system was kept under normal pressure. The decoction time was 60 minutes. Decoction completed.Afterwards, open the valve at the bottom of the extraction tank and introduce the medicinal liquid into a plate and frame filter or centrifuge through a pipeline for solid-liquid separation to obtain the first filtrate. The filter residue is retained in the extraction tank, and then drinking water equivalent to 8 times the total weight of the medicinal materials is added. The decoction temperature is controlled within the range of 90-95℃, and the decoction is carried out for 30 minutes. The liquid is then filtered again in the same way to obtain the second filtrate. After the two filtrates are combined, they are transferred to a double-effect concentrator and concentrated under reduced pressure at a vacuum degree maintained at -0.08 to -0.09 MPa. The concentration endpoint is defined as a relative density of 1.20 ± 0.05 (measured at 60℃). During the concentration process, the steam pressure is controlled within 0.1 to 0.15 MPa, and the cooling water circulation system is kept unobstructed to ensure condensation efficiency.

[0036] After the concentration is completed, the concentrate is transferred to a vacuum drying oven and dried under reduced pressure at a temperature range of 50-70℃ and a vacuum degree not lower than -0.09 MPa until the moisture content of the dry powder is no more than 5.0% as detected by a moisture analyzer. The dried material is a brown to dark brown block or granular solid. It is pulverized in a universal pulverizer and passed through a 60-100 mesh sieve to obtain a uniform and fine dry powder. The total solids yield of the dry powder is determined to be no less than 18%, indicating that the extraction process is stable and the effective components are fully retained.

[0037] In the formulation stage, different dosage forms can be selected according to clinical needs. If preparing granules, mix the above-mentioned dry extract powder with dextrin and sucrose powder in a mass ratio of 1:1:1, place in a trough mixer and stir for 5 minutes to ensure uniform mixing; then slowly add 8% polyvinylpyrrolidone (PVP) ethanol solution as a binder while stirring until a soft material that can be formed into a ball and easily dispersed under light pressure is formed; place the soft material in a vibrating granulator and granulate it through a 16-mesh stainless steel sieve to obtain wet granules; spread the wet granules evenly in a stainless steel tray and place them in a forced-air drying oven to dry at 60°C for 2 hours; after drying, the granules are sized by vibrating sieve to remove overly large or overly fine particles, and finally packaged in aluminum-plastic composite bags, each bag containing 6g of raw medicinal material.

[0038] If preparing tablets, take the dry extract powder and microcrystalline cellulose at a mass ratio of 1:0.8 and mix them in a three-dimensional motion mixer for 10 minutes. Then add sodium carboxymethyl starch (2% of the total material mass) as a disintegrant and continue mixing for 5 minutes. Finally, add 0.5% magnesium stearate as a lubricant and mix for 3 minutes to ensure uniform distribution of excipients. Feed the mixed granules into a rotary tablet press, adjust the die specifications and pressure parameters, and press them into round tablets. Each tablet contains 1.5g of raw drug, the tablet weight difference is controlled within ±5%, the hardness is between 40 and 60 N, and the disintegration time does not exceed 30 minutes.

[0039] If preparing capsules, take the above dry extract powder directly, granulate it through a 60-mesh sieve, and fill it using a fully automatic capsule filling machine.The contents of each capsule are filled into an empty capsule shell, with each capsule containing approximately 0.75g of crude drug equivalent. During the filling process, the capsule shell is pre-sterilized with ultraviolet light, and the filling environment is controlled in a Class D clean area, with temperature and humidity maintained at 20-25℃ and 45%-60% RH, respectively, to ensure product stability and hygiene standards.

[0040] Throughout the entire preparation process, all equipment is made of 316L stainless steel, and the surface roughness Ra of the parts in contact with the material is ≤0.4μm, which meets the GMP requirements for pharmaceutical equipment. Extraction, concentration, drying, pulverization, mixing, granulation, tableting, and filling processes are all completed in a workshop that complies with the Good Manufacturing Practice (GMP) for pharmaceuticals. Intermediate storage areas are set up between each process to prevent cross-contamination. Key process parameters such as decoction time, temperature, concentrated relative density, drying endpoint moisture content, mixing time, tableting pressure, and capsule filling amount are all recorded in real time by online monitoring instruments and included in the batch production record.

[0041] The traditional Chinese medicine composition of the present invention is used to treat non-proliferative diabetic retinopathy and is suitable for patients with the syndrome of liver and kidney deficiency and blood stasis in the collaterals according to traditional Chinese medicine diagnosis. The clinical manifestations of this syndrome are blurred vision, dry eyes, dizziness and tinnitus, soreness and weakness of the waist and knees, numbness of the limbs, and constipation. The tongue is dark red with little coating or with ecchymosis, and the pulse is thready and hesitant. In clinical use, the patient takes 9-18g of raw herbs orally every day, divided into 2-3 doses, for a continuous administration period of not less than 12 weeks. Granules are taken with 150-200mL of warm water (about 60°C) until completely dissolved or evenly suspended before drinking; tablets are taken with 200mL of warm water, avoiding chewing; capsules are swallowed with 200mL of warm water, and the capsule shell should not be opened.

[0042] In terms of the mechanism of action, the composition of the present invention achieves the therapeutic effect through the synergistic effect of multiple components and multiple targets. Among them, Astragalus complanatus, Tribulus terrestris, Eriocaulon buergerianum, and Equisetum hyemale together constitute the component for improving eyesight and clearing pterygium, whose chemical components mainly include flavonoids, alkaloids, and volatile oils; Salvia miltiorrhiza, Paeonia lactiflora, Polygonum cuspidatum, and Ligusticum chuanxiong constitute the component for promoting blood circulation and removing blood stasis, mainly containing active substances such as tanshinone, paeoniflorin, emodin, and tetramethylpyrazine; Cynanchum paniculatum contains coumarin compounds, which have the effect of promoting qi circulation and relieving pain; Pueraria lobata is rich in puerarin, which can dilate microvessels. After the above components are metabolized in the body, they affect the retinal microenvironment by regulating related signaling pathways. Experimental studies have shown that this composition can inhibit the expression level of vascular endothelial growth factor (VEGF) in serum, upregulate the expression of tight junction proteins Occludin and Claudin-5 between retinal microvascular endothelial cells, reduce the imbalance in the ratio of endothelial cells to pericytes, increase the density of Brn3a-positive cells in retinal ganglion cells, and improve the total thickness of the retina and the morphological structure of microvessels, thereby promoting the absorption or dissipation of fundus microaneurysms, hemorrhages, hard exudates, and capillary non-perfusion areas.

[0043] In terms of quality control, this invention establishes fingerprint spectroscopy and content determination standards for key medicinal materials. For example, using highHigh-performance liquid chromatography (HPLC) was used to determine the contents of tanshinone IIA and salvianolic acid B in *Salvia miltiorrhiza*, paeoniflorin in *Paeonia lactiflora*, puerarin in *Pueraria lobata*, emodin in *Polygonum cuspidatum*, and ferulic acid in *Ligusticum chuanxiong*, ensuring the consistency of chemical composition in each batch of products. The dry extract powder must undergo microbial limit testing (total aerobic bacteria ≤ 10³ CFU / g, total mold and yeast ≤ 10² CFU / g, no *Escherichia coli* or *Salmonella* detected), and heavy metal and harmful element residues (lead ≤ 5 mg / kg, cadmium ≤ 0.3 mg / kg, arsenic ≤ 2 mg / kg, mercury ≤ 0.2 mg / kg, copper ≤ 20 mg / kg) must comply with the requirements of the *Chinese Pharmacopoeia*.

[0044] In the stability study, three batches of pilot-scale samples were placed under accelerated testing conditions of 40±2℃ and 75%±5% relative humidity for 6 months. Samples were taken at 0, 1, 2, 3, and 6 months to test the properties, identification, inspection, content determination, and microbial limits. The results showed that all indicators met the requirements, indicating that the product has good stability under the proposed packaging conditions. The long-term retention test (25±2℃, 60%±5% RH) is underway, and preliminary 12-month data also shows that the product quality is stable.

[0045] The preparation method of the traditional Chinese medicine composition described in this invention has the characteristics of stable process, controllable operation, good reproducibility, and suitability for industrial production. All steps are based on the traditional water decoction extraction principle, without the introduction of organic solvents, and have high safety; the concentration and drying adopt the vacuum technology, which effectively preserves the heat-sensitive components; the excipients are all pharmaceutical grade, and the dosage is reasonable, which does not affect the efficacy of the main drug. The entire process, from raw material input to finished product release, includes 12 key control points, all of which have established standard operating procedures (SOPs) and validation documents.

[0046] In summary, the present invention provides a traditional Chinese medicine composition that can be used to treat non-proliferative diabetic retinopathy through clear raw material composition, precise ratio range, standardized extraction process, controllable formulation parameters and complete quality control system. The preparation method of this composition is scientific and reasonable, the product quality is stable, it is convenient for clinical use, and it has good application prospects.

[0047] In order to enable those skilled in the art to fully understand and realize the present invention, the following, combined with animal experiments, elaborates on the specific operating principle and technical effect mechanism of the traditional Chinese medicine composition of the present invention in the treatment of non-proliferative diabetic retinopathy.

[0048] Experimental Example

[0049] 1. Materials

[0050] 1.1 Drugs

[0051] SG intermediate (dry powder): batch number 20240601, Heilongjiang Jiren Pharmaceutical Co., Ltd.

[0052] Calcium dobesilate capsules: batch number 0618054, Merck Serono Ltd.

[0053] 2.2 Drug content and properties

[0054] SG intermediate (dry extract powder): yellow powder, 6.2 g crude drug / g powder.

[0055] Calcium dobesilate capsules: green and yellow two-tone capsules, with white powder and granules as contents.

[0056] 1.2 Animals

[0057] Rats, SPF grade, SD strain, 155 rats, male, initial body weight: 180-220 g. Provided by Hangzhou Medical College, animal license number SCXK (Zhejiang) 2024-0002, certificate number: 20240722Aazz0100000401, all rats are in good condition.

[0058] After the experimental animals are purchased, the experiment is started after acclimatization feeding and observation in the environment. During the acclimatization period, the growth and general performance of the animals are observed. Rat feeding environment conditions: temperature 20-24°C, humidity 40-60%, ventilation 10-20 times / h, alternating light and dark cycle 12h / 12h.

[0059] 2. Experimental Grouping

[0060] After acclimatization feeding, all rats are randomly divided into a normal group and a model group. 8 weeks after the successful establishment of diabetes model, the model group is randomly divided into 5 groups. The specific grouping is as follows:

[0061] (1) Normal group;

[0062] (2) Model group;

[0063] (3) Low-dose SG group of clinical prescription (hereinafter referred to as low-dose group);

[0064] (4) Medium-dose SG group of clinical prescription (hereinafter referred to as medium-dose group);

[0065] (5) High-dose SG group of clinical prescription (hereinafter referred to as high-dose group);

[0066] (6) Positive control drug group for diabetic retinopathy (hereinafter referred to as calcium dobesilate group).

[0067] 3. Experimental Procedure

[0068] SPF-grade SD male rats with body mass of 180-220 g and age of 6-8 weeks are selected. After 7 days of acclimatization feeding, except for 8 rats in the normal group, 147 rats in the model group are fed with high-sugar and high-fat diet for 4 weeks, while rats in the normal group are fed with normal diet. After 4 weeks, all rats are fasted but allowed free access to water for 12 h. Each model rat is intraperitoneally injected with STZ at a dose of 35 mg / kg, and the normal group is intraperitoneally injected with an equal volume of DESCRIPTION Page 6 / 25 8 CN 122537462 A citrate buffer. After 72 h, blood is collected from the tail tip to measure blood glucose, and the random blood glucose (RBG) of rats in each model group is measured. Rats with RBG≥16.7 mmol / L are selected for subsequent research. One week after STZ injection, the rats are fasted for 6 h to detect the fasting blood glucose (FBG) of rats in the model group. FBG≥11.1 mmol / L is regarded as successful modeling of type 2 diabetes. The successfully modeled type 2 diabetic rats are continued to be fed with high-sugar and high-fat diet. 8 weeks after the successful modeling of type 2 diabetes, blood glucose is detected, and rats with unqualified blood glucose are excluded. According to body weight and blood glucose, the remaining model rats are randomly divided into model group, low-, medium- and high-dose SG groups of clinical prescription (300, 599, 1198 mg / kg),The positive control group for diabetic retinopathy (calcium dobesilate group, 130mg / kg) was administered for 7 weeks. Three rats were randomly selected from the normal group according to their weight and blood glucose. Four rats were selected from the model group and the clinical prescription SG low, medium and high dose groups (300, 599, 1198mg / kg) and calcium dobesilate group (130mg / kg) for various index detection. The remaining animals in each group continued to be administered the drug. After 12 weeks of administration, the remaining animals in each group were processed for various index detection.

[0069] 4. Observation indicators

[0070] (1) Observation of general condition of rats: daily weight, food intake and water intake were measured.

[0071] (2) Detection of blood glucose related indicators

[0072] ① Fasting blood glucose (FBG): FBG of rats in each group was measured by blood collection from the tail tip 1 week, 9 weeks after STZ injection and 7 weeks and 12 weeks after administration.

[0073] ② Random blood glucose (RBG): RBG of rats in each group was measured by blood collection from the tail tip 72h, 9 weeks after STZ injection, and 7 and 12 weeks after administration.

[0074] ③ Glycated hemoglobin (GHb): GHb of randomly selected rats in each group was measured by blood collection from the abdominal aorta 7 weeks after administration; GHb of the remaining rats in each group was measured by blood collection from the abdominal aorta 12 weeks after administration.

[0075] ④ Serum fasting insulin (Insulin), insulin resistance index (HOMA-IR), and insulin sensitivity index (ISI) measurement: 3 rats were randomly selected from the normal group 7 weeks after administration, and 4 rats were randomly selected from the model group, the low, medium, and high dose groups of the clinical prescription SG, and the calcium dobesilate group. The animals were fasted for 12h but allowed free water, and blood was collected from the abdominal aorta for insulin measurement; GHb of the remaining animals in each group was fasted for 12h but allowed free water, and blood was collected from the abdominal aorta for insulin measurement. The fasting insulin level (INS) of each rat was measured according to the instructions of the rat ELISA kit, and the insulin resistance index and insulin sensitivity index of each group of rats were calculated after the administration. The calculation method is as follows: HOMA-IR=FBG×INS / 22.51; ISI=Ln(1 / (INS×FBG)); where FBG: fasting blood glucose concentration mmol / L; INS: fasting insulin concentration mU / L.

[0076] (3) Detection of diabetic retinopathy related indicators

[0077] ①HE staining

[0078] After 7 weeks of administration, 3 rats were randomly selected from the normal group, and 4 rats were randomly selected from the model group, the low, medium and high dose groups of the clinical prescription SG and the calcium dobesilate group. The rats were anesthetized with urethane, and the right eyeballs of each group of animals were removed. The eyeballs were fixed with FAS fixative, embedded in paraffin and sectioned. When sectioning, the intact retina near the optic nerve was located for longitudinal sectioning to make the sections comparable. HE staining, observation and photography were performed under an optical microscope. 3 test points were randomly selected from each section, and the average retinal thickness was calculated.

[0079] Twelve weeks after administration of urethane, rats were anesthetized, and the right eyeballs of the remaining animals in each group were harvested. The eyeballs were fixed with FAS fixative, embedded in paraffin, and sectioned. During sectioning, longitudinal sections were made on intact retina near the optic nerve to ensure comparability between sections. The sections were stained with hematoxylin and eosin (HE), observed and photographed under an optical microscope. Three test points were randomly selected from each section, and the average retinal thickness was calculated.

[0080] ②Retinal digestion slides

[0081] After 7 weeks of drug administration, 3 rats were randomly selected from the normal group, and 4 rats were selected from the model group, the low, medium and high dose groups of the clinical prescription SG, and the calcium dobesilate group. The left eyeball tissue of each group of rats was taken, fixed in 4% paraformaldehyde solution for 12 hours, and the retina was separated. It was then incubated in 8% trypsin solution for 2 hours for digestion. It was placed in a constant temperature water bath at 37°C, and every 1 hour, the excess tissue was washed with a pipette until only the transparent retinal vascular network remained. The tissue was then aspirated and stained with PAS. The morphology of the retinal vessels was observed under a microscope. Retinal slides of each group of rats were taken. Using a cell image analyzer, 3 fields of view were taken from the left side of each retinal slide to count the number of pericytes, endothelial cells and cell-free capillaries of the retinal microvessels.

[0082] After 12 weeks of drug administration, the remaining left eyeball tissue of each group of rats was taken, fixed in 4% paraformaldehyde solution for 12 hours, and after separating the retina, it was incubated in 8% trypsin solution for 2 hours for digestion. It was then placed in a constant temperature water bath at 37°C, and every 1 hour, it was pipetted to wash away excess tissue until only the transparent retinal vascular network remained. The tissue was then aspirated and stained with PAS, and the morphology of retinal vessels was observed under a microscope. Retinal slices of each group of rats were taken, and three fields of view were taken from the left side of each retinal slice using a cell image analyzer to count the number of pericytes, endothelial cells and cell-free capillaries of retinal microvessels.

[0083] ③ Blood-retinal barrier function detection

[0084] After digesting the retinal slices, the expression of tight junction proteins Occludin and Claudin-5 in the retinal vascular network was detected by immunohistochemistry. Retinal vascular digestion slides were washed with PBS to block endogenous peroxidase, primary antibody was added, and incubated overnight at 4°C. Secondary antibody was added, DAB staining was performed, hematoxylin staining was used for counterstaining, gradient alcohol was used for dehydration, xylene was used for clearing, and neutral resin was used for mounting. The slides were observed and photographed under an optical microscope.

[0085] ④ Immunohistochemical staining to detect Brn3a protein expression in rat retinal tissue

[0086] Retinal paraffin sections were dewaxed, and then placed in xylene I and xylene II for 15 min each, followed by anhydrous ethanol I, anhydrous ethanol II, 95%, 85%, 75%, and 50% gradient ethanol for 2 min each, and then in pure water for 2 min. The sections were then placed in the prepared antigen retrieval solution and microwaved from medium to high for 20 min. After cooling to room temperature, the sections were rinsed with PBS for 3 min, dried, and then 3% peroxide was added.Incubate with hydrogen peroxide in the dark for 20 min, rinse three times with PBS for 2 min each time, spin dry, block with goat antiserum for 1 h, add primary antibody and incubate overnight at 4°C. Place at room temperature, rinse three times with PBS for 2 min each time, spin dry, add HRP secondary antibody and incubate for 30 min, rinse three times with PBS for 2 min each time, spin dry, add DAB (kit) under dark conditions for color development, stop the reaction when the tissue turns brown, wash with water for 1 min, spin dry, counterstain with hematoxylin for 5 min, rinse with tap water to return to blue. Sequentially immerse in pure water, 50%, 75%, 85%, 95% graded ethanol for 2 min, anhydrous ethanol II and anhydrous ethanol I for 2 min each, clear with xylene II and xylene I for 10 min, wipe dry, mount with neutral resin, acquire images under a microscope, and count Brn3a-positive retinal ganglion cells.

[0087] ⑤ ELISA detection of serum vascular endothelial growth factor (VEGF) level

[0088] After 7 weeks of administration, 3 rats were randomly selected from the normal group, and 4 rats were randomly selected from the model group, the low, medium and high dose groups of clinical prescription SG, and the calcium dobesilate group. The rats were anesthetized with urethane, and blood was collected from the abdominal aorta of the rats. The serum was separated and the VEGF level in the serum was measured.

[0089] After 12 weeks of administration, the remaining rats in each group were anesthetized with urethane, and blood was collected from the abdominal aorta of the rats. The serum was separated and the VEGF level in the serum was measured.

[0090] 5. Results

[0091] 5.1 Effects of SG on body weight, food intake and water intake of type 2 diabetic rats

[0092] Description of animal model formation and grouping:

[0093] 72 h after STZ injection, 128 rats met the requirement of RBG≥16.7mmol / L; 1 week after STZ injection, 119 rats met the requirement of FBG≥11.1mmol / L.

[0094] At 8 weeks of modeling type 2 diabetes, a total of 16 rats died (the cause of death may be ketoacidosis caused by hyperglycemia). Random blood glucose and fasting blood glucose were tested in the model group rats. Three rats with unqualified blood glucose were removed, and a total of 100 rats had blood glucose that met the requirements. The 100 rats in the model group were divided into the following groups: model group (20 rats), clinical prescription SG low-dose group (20 rats), clinical prescription SG medium-dose group (20 rats), clinical prescription SG high-dose group (20 rats), and calcium dobesilate group (20 rats). Instructions for use 8 / 25 pages 10 CN 122537462 A

[0095] At 7 weeks of administration, the number of rats remaining in each group was as follows: normal group 8 rats, model group 12 rats, clinical prescription SG low-dose group 11 rats, clinical prescription SG medium-dose group 13 rats, clinical prescription SG high-dose group 13 rats, and calcium dobesilate group 14 rats. Three animals were randomly selected from the normal group based on their weight and blood glucose levels, and four animals were selected from the model group, as well as the low, medium, and high dose clinical prescription SG groups and the calcium dobesilate group, for the detection of various indicators; the remaining animals in each group continued to be administered the medication.

[0096] At 12 weeks of administration, the remaining rat numbers in each group were as follows: normal group (5 rats), model group (5 rats), clinical prescription SG low-dose group (5 rats), clinical prescription SG medium-dose group (6 rats), clinical prescription SG high-dose group (6 rats), and calcium dobesilate group (7 rats).

[0097] 5.1.1 Changes in rat body weight, food intake, and water intake before administration

[0098] During the adaptive feeding and high-sugar, high-fat induction period in the model group, the body weight of rats in each group gradually increased; by week 4 of high-sugar, high-fat induction, the body weight of rats in the model group was significantly higher than that in the normal group (P<0.05). After STZ injection, the body weight of rats in the normal group steadily increased, while after STZ injection, the body weight of rats in the model group was significantly lower than that in the normal group (P<0.001). The results are shown in Table 1.

[0099] During the adaptive feeding and high-sugar, high-fat induction period of the model group, as the weight of rats in each group gradually increased, their average food intake and average water intake slowly decreased, and there were no statistically significant differences in weight, average food intake, and average water intake between the two groups (P>0.05). After STZ injection, compared with the normal group, the average food intake and average water intake of rats in the model group increased significantly (P<0.001). The results are shown in Tables 2 and 3.

[0100] Table 1 Average weight of rats in each group before administration (Mean±SD, g / rat)

[0101]

[0102] Note: Compared with the normal group, *P<0.05, ***P<0.001.

[0103] Table 2 Average food intake of rats in each group before drug administration (Mean±SD, g / 100g BW) Instruction manual 9 / 25 page 11 CN 122537462 A

[0104]

[0105] Note: Compared with the normal group, ***P<0.001.

[0106] Due to fasting during the fourth week of high-fat feeding, only 6 days of food intake data were collected, and the number of animals in each group is the same as in Table 1.

[0107] Table 3 Average water intake of rats in each group before drug administration (Mean±SD, mL / 100g BW) Instruction manual 10 / 25 page 12 CN 122537462 A

[0108]

[0109] Note: Compared with the normal group, **P<0.01, ***P<0.001.

[0110] Due to fasting during the fourth week of high-fat feeding, only 6 days of water intake data were collected, and the number of animals in each group is the same as in Table 1.

[0111] 5.1.2 Changes in body weight, food intake, and water intake of rats in each group after drug administration

[0112] During the 7-week drug administration period, the body weight of rats in the normal group steadily increased. Compared with the normal group, the body weight of the model group and each drug administration group was significantly reduced (P<0.001), and there was no significant statistical difference between the model group and each drug administration group (P>0.05). During the 12-week drug administration period, the body weight of rats in the normal group steadily increased. Compared with the normal group, the body weight of the model group and each drug administration group was significantly reduced (P<0.001), and there was no significant statistical difference between the model group and each drug administration group (P>0.05). The results are shown in Table 4.

[0113] After 7 weeks of administration, 3 rats were randomly selected from the normal group according to their body weight and blood glucose, and 4 rats were randomly selected from the model group, the low-, medium-, and high-dose clinical prescription SG groups, and the calcium dobesilate group for various index tests. There was no statistically significant difference in body weight between the treated rats and the remaining rats (P>0.05). The results are shown in Table 5.

[0114] During the 7-week administration period, compared with the normal group, the average food intake and average water intake of the model group and each administration group increased significantly (P<0.001), and there was no statistically significant difference between the model group and each administration group (P>0.05). During the 12-week administration period, compared with the normal group, the average food intake and average water intake of the model group and each administration group increased significantly (P<0.001), and there was no statistically significant difference between the model group and each administration group (P>0.05). The results are shown in Tables 6 and 7.

[0115] Table 4 Average body weight of rats in each group after administration (Mean±SD, g / rat) Instructions for use, page 11 / 25, 13 CN 122537462 A

[0116]

[0117] Note: Compared with the normal group, ***P<0.001.

[0118] Instructions for use, page 12 / 25, 14 CN 122537462 A

[0119]

[0120] Table 4 Average body weight of rats in each group after administration (Mean±SD, g / rat) (continued)

[0121] Note: Compared with the normal group, ***P<0.001.

[0122] Table 5 Average body weight of treated rats and remaining rats in each group 7 weeks after administration (Mean±SD, g / rat)

[0123]

[0124] Note: Compared with the normal group, ***P<0.001.

[0125] Table 6 Average food intake of rats in each group after administration (Mean±SD, g / 100g BW) Instructions for use, page 13 / 25, CN 122537462 A

[0126]

[0127] Note: Compared with the normal group, ***P<0.001. Due to the animals being fasted for 5 days in the seventh and twelfth weeks after administration, the number of animals in each group is the same as in Table 4.

[0128] Table 7 Average water intake of rats in each group after administration (Mean±SD, mL / 100g BW) Instructions for use, page 14 / 25, CN 122537462 A

[0130]

[0131] Note: Compared with the normal group, ***P<0.001. Due to the animals being fasted for 5 days in the seventh and twelfth weeks after administration, the number of animals in each group is the same as in Table 4.

[0133] 5.2 Effect of SG on blood glucose in type 2 diabetic rats

[0134] 5.2.1 Changes in blood glucose in each group of rats before administration

[0135] 72 hours after STZ injection, 128 out of 147 model rats met the requirement of RBG ≥ 16.7 mmol / L. One week after STZ injection, 119 rats met the requirement of FBG ≥ 11.1 mmol / L.

[0136] Eight weeks after the establishment of the type 2 diabetes model, a total of 16 rats died. Random blood glucose and fasting blood glucose were measured in the model group rats. After removing 3 rats with unqualified blood glucose, a total of 100 rats met the blood glucose requirements. The random blood glucose and fasting blood glucose of the model group rats were maintained at high levels, and there were extremely significant statistical differences compared with the normal group (P < 0.001). The results are shown in Table 8.

[0137] Table 8 Blood glucose of each group of rats before administration (Mean ± SD, mmol / L)

[0138]

[0139] Note: Compared with the normal group, ***P < 0.001.

[0140] 5.2.2 Changes in blood glucose levels in rats after administration

[0141] Seven weeks after administration, blood glucose levels in each group of rats were measured again. The random blood glucose and fasting blood glucose levels in each group of rats remained at high levels, showing extremely significant statistical differences (P < 0.001). Compared with the model group, there were no significant changes in blood glucose levels in each administration group, and no significant statistical differences (P > 0.05). Three rats were randomly selected from the normal group according to their weight and blood glucose, and four rats were selected from the model group, the low, medium, and high dose groups of the clinical prescription SG, and the calcium dobesilate group, respectively. There were no significant statistical differences in blood glucose levels between the treated rats and the remaining rats (P > 0.05). The results are shown in Tables 9 and 10.

[0142] Twelve weeks after administration, blood glucose levels in each group of rats were measured again. The random blood glucose and fasting blood glucose levels in each group of rats remained at high levels, showing extremely significant statistical differences (P < 0.001). Compared with the model group, there were no significant statistical differences in blood glucose levels in each administration group (P > 0.05). The results are shown in Table 11.

[0143] Table 9 Blood glucose (Mean±SD, mmol / L) of rats in each group after 7 weeks of administration

[0144]

[0145] Note: Compared with the normal group, ***P<0.001.

[0146] Table 10 Blood glucose (Mean±SD, mmol / L) of treated rats and remaining rats in each group after 7 weeks of administration Instructions for Use 16 / 25 pages 18 CN 122537462 A

[0147]

[0148] Note: Compared with the normal group, ***P<0.001

[0149] Table 11 Blood glucose (Mean±SD, mmol / L) of rats in each group after 12 weeks of administration

[0150]

[0151]

[0152] Note: Compared with the normal group, ***P<0.001.

[0153] 5.3 Effects of SG on serum fasting insulin, insulin resistance index and insulin sensitivity index in type 2 diabetic rats

[0154] 5.3.1 Changes in serum fasting insulin, insulin resistance index, and insulin sensitivity index in rats after drug administration

[0155] After 7 weeks of drug administration, compared with the normal group, the serum fasting insulin level and insulin resistance index in the model group and each drug administration group were significantly increased (P<0.001), and the insulin sensitivity index was significantly decreased (P<0.01); compared with the model group, there were no significant changes in fasting insulin level, insulin resistance index, and insulin sensitivity index in each drug administration group, and there were no statistically significant differences (P>0.05). The results are shown in Table 12.

[0156] After 12 weeks of administration, compared with the normal group, the serum fasting insulin level and insulin resistance index of the model group and each administration group were significantly increased (P<0.001), and the insulin sensitivity index was significantly decreased (P<0.001); compared with the model group, there were no significant changes in fasting insulin level, insulin resistance index and insulin sensitivity index of each administration group, and no significant statistical differences (P>0.05). The results are shown in Table 13.

[0157] Table 12 Fasting insulin, HOMA-IR and ISI (Mean±SD) of rats in each group after 7 weeks of administration

[0158]

[0159] Note: Compared with the normal group, *P<0.05, **P<0.01, ***P<0.001.

[0160] Table 13 Fasting insulin, HOMA-IR and ISI (Mean±SD) of rats in each group after 12 weeks of administration

[0161]

[0162] Note: Compared with the normal group, ***P<0.001.

[0163] 5.4 Effect of SG on glycated hemoglobin level in type 2 diabetic rats

[0164] After 7 weeks of administration, compared with the normal group, the glycated hemoglobin level in the model group and each administration group was significantly increased (P<0.001); compared with the model group, the glycated hemoglobin level in each administration group did not change significantly, and there was no statistically significant difference (P>0.05). The results are shown in Table 14.

[0165] After 12 weeks of administration, compared with the normal group, the glycated hemoglobin level in the model group and each administration group was significantly increased (P<0.001); compared with the model group, the glycated hemoglobin level in each administration group did not change significantly, and there was no statistically significant difference (P>0.05). The results are shown in Table 15.

[0166] Table 14 Glycated hemoglobin (Mean±SD, %) in rats of each group after 7 weeks of drug administration. (Instructions for use, page 18 / 25, 20 CN 122537462 A)

[0167]

[0168] Note: Compared with the normal group, ***P<0.001.

[0169] Table 15 Glycated hemoglobin (Mean±SD, %) in rats of each group after 12 weeks of drug administration.

[0170]

[0171]

[0172] Note: Compared with the normal group, ***P<0.001.

[0173] 5.5 Effects of SG on retinopathy in type 2 diabetic rats

[0174] 5.5.1 Changes in retinal pathological morphology in rats after administration

[0175] After 7 weeks of administration, compared with the normal group, the model group rats showed disordered retinal structure, unclear layers, loose and irregular cell arrangement in each layer, and a significantly reduced total retinal thickness (P<0.001). Compared with the model group, the medium and high dose SG groups and the calcium dobesilate group improved the pathological changes such as disordered retinal structure, unclear layers, and loose and irregular cell arrangement in each layer in type 2 diabetic rats. Among them, the medium and high dose SG groups significantly increased the total retinal thickness (P<0.01), and the calcium dobesilate group significantly increased the total retinal thickness (P<0.001). The results are shown in Table 16 and Figure 1.

[0176] After 12 weeks of administration, compared with the normal group, the model group rats showed disordered retinal structure, unclear layers, loose and irregular cell arrangement in each layer, and a significantly reduced total retinal thickness (P<0.001). Compared with the model group, the low, medium, and high dose SG groups and the calcium dobesilate group improved the pathological changes such as disordered retinal structure, unclear layers, and loose and irregular cell arrangement in type 2 diabetic rats. Among them, the low dose SG group significantly increased the total retinal thickness (P<0.05), and the medium and high dose SG groups and the calcium dobesilate group showed extremely significant increases in total retinal thickness (P<0.001). The results are shown in Table 17 and Figure 2.

[0177] Table 16 Total retinal thickness of rats in each group after 7 weeks of administration (Mean±SD, μm) Instructions for use 19 / 25 pages 21 CN 122537462 A

[0178]

[0179] Note: Compared with the normal group, **P<0.01, ***P<0.001; compared with the model group, ##P<0.01, ###P<0.001.

[0180] Table 17 Total retinal thickness (Mean±SD, μm) of rats in each group after 12 weeks of administration

[0181]

[0182] Note: Compared with the normal group, ***P<0.001; compared with the model group, #P<0.05, ###P<0.001.

[0183] 5.5.2 Changes in retinal microvascular morphology of rats in each group after administration

[0184] After 7 weeks of administration, compared with the normal group, the retinal vessels of rats in the model group were tortuous, acellular vessels appeared, and the ratio of endothelial cells to pericytes was significantly increased (P<0.001). Compared with the model group, the high-dose SG group and the calcium dobesilate group improved the tortuous retinal vessels and acellular vessels in type 2 diabetic rats. Among them, the high-dose SG group significantly reduced the ratio of endothelial cells to pericytes (P<0.01), and the calcium dobesilate group significantly reduced the ratio of endothelial cells to pericytes (P<0.001). The results are shown in Table 18 and Figure 3.

[0185] After 12 weeks of drug administration, compared with the normal group, the retinal vessels in the model group rats were tortuous, with acellular vessels appearing, and the ratio of endothelial cells to pericytes was significantly increased (P<0.001). Compared with the model group, the medium- and high-dose SG groups and the calcium dobesilate group improved the pathological changes such as tortuous retinal vessels and acellular vessels in type 2 diabetic rats. Among them, the medium-dose SG group significantly reduced the ratio of endothelial cells to pericytes (P<0.01), and the high-dose SG group and the calcium dobesilate group significantly reduced the ratio of endothelial cells to pericytes (P<0.001). The results are shown in Table 19 and Figure 4.

[0186] Table 18 Endothelial cell / peripheral cell ratio in rats after 7 weeks of drug administration (Mean±SD) Instructions for use 20 / 25 pages 22 CN 122537462 A

[0187]

[0188]

[0189] Note: Compared with the normal group, *P<0.05, ***P<0.001; compared with the model group, ##P<0.01, ###P<0.001.

[0190] Table 19 Endothelial cell / peripheral cell ratio in rats after 12 weeks of drug administration (Mean±SD)

[0191]

[0192] Note: Compared with the normal group, **P<0.01, ***P<0.001; compared with the model group, ##P<0.01, ###P<0.001.

[0193] 5.5.3 Changes in blood-retinal barrier function in rats after drug administration

[0194] After 7 weeks of drug administration, compared with the normal group, the expression of Occludin and Claudin-5, the tight junction proteins of retinal microvascular tissue cells in the model group rats, was significantly decreased (P<0.001). Compared with the model group, the expression of Occludin, the tight junction protein of retinal microvascular tissue cells in the high-dose SG group rats was significantly upregulated (P<0.05), and the expression of Occludin, the tight junction protein of retinal microvascular tissue cells in the calcium dobesilate group rats was significantly upregulated (P<0.01); the expression of Claudin-5, the tight junction protein of retinal microvascular tissue cells in the medium-dose SG group rats was significantly upregulated (P<0.01), and the expression of Claudin-5, the tight junction protein of retinal microvascular tissue cells in the high-dose SG group and the calcium dobesilate group rats was significantly upregulated (P<0.001). The results are shown in Table 20, Figure 5, and Figure 7.

[0195] After 12 weeks of drug administration, compared with the normal group, the expression of Occludin, a tight junction protein in the retinal microvascular tissue cells of rats in the model group was significantly decreased (P<0.01), and the expression of Claudin-5 was significantly decreased (P<0.001). Compared with the model group, the expression of Occludin, a tight junction protein between retinal microvascular tissue cells of rats in the medium-dose SG group was significantly upregulated (P<0.05).The expression of ocludin, a tight junction protein between cells in the retinal microvessels of rats in the high-dose SG group and the calcium dobesilate group, was significantly upregulated (P<0.01); the expression of claudin-5, a tight junction protein between cells in the retinal microvessels of rats in the medium-dose SG group, was significantly upregulated (P<0.05); the expression of claudin-5, a tight junction protein between cells in the retinal microvessels of rats in the high-dose SG group, was significantly upregulated (P<0.01); and the expression of claudin-5, a tight junction protein between cells in the retinal microvessels of rats in the calcium dobesilate group, was significantly upregulated (P<0.001). The results are shown in Table 21, Figure 6, and Figure 8.

[0196] Table 20 Mean optical density values ​​(Mean ± SD) of occludin and claudin-5 in the retinal microvessels of rats in each group after 7 weeks of drug administration

[0197]

[0198] Note: Compared with the normal group, *P<0.05, **P<0.01, ***P<0.001; compared with the model group, #P<0.05,

[0199] ##P<0.01, ###P<0.001.

[0200] Table 21 Mean optical density values ​​(Mean ± SD) of occludin and claudin-5 in the retinal microvessels of rats in each group after 12 weeks of drug administration

[0201]

[0202] Note: Compared with the normal group, *P<0.05, **P<0.01, ***P<0.001; compared with the model group, #P<0.05,

[0203] ##P<0.01, ###P<0.001.

[0204] 5.5.4 Changes in retinal ganglion cell density in each group of rats after administration

[0205] After 7 weeks of administration, compared with the normal group, the density of Brn3a-positive cells, a marker protein of retinal ganglion cells, was significantly decreased in the model group (P<0.001). Compared with the model group, the density of ganglion cells in the retinal tissue of rats in the medium-dose SG group was significantly increased (P<0.05), and the density of ganglion cells in the retinal tissue of rats in the high-dose group and the calcium dobesilate group was significantly increased (P<0.001). The results are shown in Table 22 and Figure 9.

[0206] After 12 weeks of administration, compared with the normal group, the density of Brn3a-positive cells, a marker protein of retinal ganglion cells, was significantly decreased in the model group (P<0.001). Compared with the model group, the density of ganglion cells in the retinal tissue of rats in the low-dose SG group was significantly increased (P<0.05), and the density of ganglion cells in the retinal tissue of rats in the medium- and high-dose SG groups and the calcium dobesilate group was extremely significantly increased (P<0.001). The results are shown in Table 23 and Figure 10.

[0207] Table 22 Density of Brn3a positive cells in the retina of rats in each group after 7 weeks of administration (Mean±SD, cells / mm2) Instructions for use 22 / 25Page 24 CN 122537462 A

[0208]

[0209] Note: Compared with the normal group, *P<0.05, ***P<0.001; compared with the model group, #P<0.05, ###P<0.001.

[0210] Table 23 Density of Brn3a positive cells in the retina of rats in each group after 12 weeks of administration (Mean±SD, cells / mm2)

[0211]

[0212] Note: Compared with the normal group, *P<0.05, ***P<0.001; compared with the model group, #P<0.05, ###P<0.001.

[0213] 5.5.5 Changes in VEGF levels in the serum of rats in each group after administration

[0214] After 7 weeks of administration, compared with the normal group, the VEGF level in the serum of rats in the model group was significantly increased (P<0.001). Compared with the model group, the serum VEGF level in the high-dose SG group was significantly decreased (P<0.01), and the serum VEGF level in the calcium dobesilate group was significantly decreased (P<0.001). The results are shown in Table 24.

[0215] After 12 weeks of administration, compared with the normal group, the serum VEGF level in the model group was significantly increased (P<0.001). Compared with the model group, the serum VEGF levels in the low, medium, and high-dose SG groups and the calcium dobesilate group were all significantly decreased (P<0.001). The results are shown in Table 25.

[0216] Table 24 Serum vascular endothelial growth factor (VEGF) levels in rats after 7 weeks of drug administration (Mean±SD, pg / mL) Instructions for use 23 / 25 pages 25 CN 122537462 A

[0217]

[0218] Note: Compared with the normal group, *P<0.05, ***P<0.001; compared with the model group, ##P<0.01, ###P<0.001.

[0219] Table 25 Serum vascular endothelial growth factor (VEGF) levels in rats after 12 weeks of drug administration (Mean±SD, pg / mL)

[0220]

[0221] Note: Compared with the normal group, *P<0.05, ***P<0.001; compared with the model group, ###P<0.001.

[0222] 6 Discussion

[0223] Diabetic retinopathy is one of the most common microvascular complications of diabetes. It is caused by leakage and blockage of retinal microvessels due to chronic progressive diabetes, resulting in a series of fundus lesions, such as microaneurysms, hard exudates, cotton wool spots, neovascularization, vitreous proliferation, macular edema, and even retinal detachment [2-4]. The most common early clinical manifestations of diabetic retinopathy include microaneurysm formation and intraretinal hemorrhage. Microvascular damage leads to retinal capillary nonperfusion, cotton wool spots, increased number of hemorrhages, venous abnormalities, and intraretinal microvascular abnormalities. At this stage, increased vascular permeability will...This leads to retinal thickening (edema) and / or exudation, resulting in decreased central vision. The proliferative phase leads to the proliferation of new blood vessels in the optic disc, retina, iris, and filtration angle. These new blood vessels then lead to tractional retinal detachment and neovascular glaucoma, respectively [5]. Commonly used animal models for inducing early diabetic retinopathy are mainly induced by long-term high-sugar and high-fat diets, or by high-sugar and high-fat diets combined with STZ injections. Long-term high-sugar and high-fat diets have a long time period. C57BL / 6J mice showed diabetic retinopathy after 20 weeks of continuous high-sugar and high-fat diets, and early retinopathy features such as increased retinal vascular permeability appeared after 48 weeks [6]. Related studies have shown that animal models induced by high-sugar and high-fat diets combined with STZ injections show early retinopathy features in 8-10 weeks. Animal models of diabetic proliferative retinopathy are mainly constructed by hyperoxia-induced neovascularization of the mouse retina [7]. The commonly used animal model for type 2 diabetic retinopathy is the high-sugar, high-fat combined STZ-induced type 2 diabetic animal model. Previous studies have shown that early diabetic retinopathy appears about 8 weeks after the establishment of the type 2 diabetic model (pages 24 / 25, CN 122537462 A). Therefore, this experiment uses the high-sugar, high-fat combined STZ-induced type 2 diabetic animal model to preliminarily explore the therapeutic effect of SG on type 2 diabetic retinopathy.

[0224] Early diabetic retinopathy is mainly evaluated by HE staining, PAS staining, blood-retinal barrier function detection, and retinal nerve function detection. HE staining is a commonly used method for observing retinal structure. In the state of diabetic retinopathy, the overall thickness of the retina is thinner, the retinal structure is disordered, the layers are unclear, the cells in each layer are loosely and irregularly arranged, and the intercellular spaces are widened. PAS staining is used to observe the pathological morphological changes of retinal vessels. The staining results show that the ratio of retinal microvascular endothelial cells to pericytes is increased, indicating pericyte loss, which is a marker of early histopathology of diabetic retinopathy. The reduction of pericytes eventually stimulates the generation of retinal neovascularization. Increased retinal permeability caused by blood-retinal barrier disruption is a significant marker of the early stage of diabetic retinopathy. Changes in blood-retinal barrier function are mainly detected by Evans blue leakage assay and immunohistochemical quantitative tight junction expression. Retinal neuropathy is an early event in the pathogenesis of diabetic retinopathy. Brn3a is a marker protein of retinal ganglion cells. Changes in ganglion cells are detected by immunohistochemical staining or immunofluorescence staining for Brn3a to determine the degree of diabetic retinopathy [8-10].

[0225] For early diabetic retinopathy, after 7 weeks of SG intervention, the medium-dose SG group (clinically equivalent dose group) improved the structural disorder, unclear layers, and loose cell arrangement in the retinal tissue of type 2 diabetic rats.The high-dose SG group (2 times the clinically equivalent dose) significantly increased the total retinal thickness, elevated the expression of the tight junction protein Claudin-5, improved the blood-retinal barrier function, and increased the density of ganglion cells in the retinal tissue, thus improving the pathological changes such as structural disorder, unclear layers, and loose and irregular cell arrangement in the retinal tissue of type 2 diabetic rats. It also significantly increased the total retinal thickness, decreased the ratio of endothelial cells to pericytes, significantly increased the expression of the tight junction proteins Occludin and Claudin-5, improved the blood-retinal barrier function, significantly increased the density of ganglion cells in the retinal tissue, and decreased serum VEGF levels. These findings suggest that 7 weeks of administration of the high-dose SG group has a therapeutic effect on early diabetic retinopathy.

[0226] In the treatment of early diabetic retinopathy, after 12 weeks of SG intervention, the low-dose SG group (1 / 2 times the clinical equivalent dose) improved the pathological changes in the retinal tissue of type 2 diabetic rats, such as structural disorder, unclear layers, and loose and irregular cell arrangement in each layer. It significantly increased the total thickness of the retina and the density of ganglion cells in the retinal tissue, and reduced the serum VEGF level. The medium-dose SG group (clinical equivalent dose) and the high-dose SG group (2 times the clinical equivalent dose) also improved the pathological changes in the retinal tissue of type 2 diabetic rats, such as structural disorder, unclear layers, and loose and irregular cell arrangement in each layer. They significantly increased the total thickness of the retina, reduced the ratio of endothelial cells to pericytes, significantly increased the expression of the intercellular tight junction proteins Occludin and Claudin-5, and significantly increased the density of ganglion cells in the retinal tissue, and reduced the serum VEGF level. This suggests that SG low, medium, and high doses administered for 12 weeks have a therapeutic effect on early diabetic retinopathy.

[0227] 7. Experimental Conclusions

[0228] (1) After 7 weeks of SG intervention treatment, the high-dose SG group had a therapeutic effect on early diabetic retinopathy.

[0229] (2) After 12 weeks of SG intervention treatment, the low, medium, and high-dose SG groups had a therapeutic effect on early diabetic retinopathy. (The remaining text appears to be a list of references and related information, which are not translated as they are not part of the main text.)122537462 A Abstract The present application relates to the technical field of traditional Chinese medicine preparations, in particular to a traditional Chinese medicine composition for treating nonproliferative diabetic retinopathy, its preparation method and application. The composition comprises Semen Astragali Complanati, Fructus Tribuli, Flos Eriocauli, Herba Equiseti Hiemalis, Radix Salviae Miltiorrhizae, Radix Paeoniae Rubra, Rhizoma Polygoni Cuspidati, Radix Cynanchi Paniculati, Rhizoma Chuanxiong and Radix Puerariae. The composition improves ocular fundus microangiopathy through multi-effect synergy such as tonifying liver and eyesight, promoting blood circulation and removing blood stasis, dredging collaterals and relieving pain. The preparation method comprises water extraction, concentration and drying to obtain dry extract powder, which is further formulated into granules, tablets or capsules. The composition is clinically applicable to the syndrome of liver-kidneydeficiency and collateral stasis. It can inhibit the expression of Vascular Endothelial Growth Factor (VEGF), repair retinal barrier function, and promote the absorption of microaneurysms and exudates.

Claims

1. A traditional Chinese medicine composition for treating non-proliferative diabetic retinopathy, characterized in that, The traditional Chinese medicine composition consists of Astragalus complanatus, Tribulus terrestris, Eriocaulon buergerianum, Equisetum hyemale, Salvia miltiorrhiza, Paeonia lactiflora, Polygonum cuspidatum, Cynanchum paniculatum, Ligusticum chuanxiong, and Pueraria lobata.

2. The traditional Chinese medicine composition according to claim 1, characterized in that, By weight, the following ingredients are used: Astragalus complanatus 2-10 parts, Tribulus terrestris 2-10 parts, Eriocaulon buergerianum 2-10 parts, Equisetum hyemale 1-5 parts, Salvia miltiorrhiza 3-15 parts, Paeonia lactiflora 3-15 parts, Polygonum cuspidatum 2-10 parts, Cynanchum paniculatum 1-10 parts, Ligusticum chuanxiong 2-10 parts, and Pueraria lobata 1-5 parts.

3. The traditional Chinese medicine composition according to claim 2, characterized in that, The traditional Chinese medicine composition, by weight, consists of 4.5 parts of Astragalus complanatus, 4.5 parts of Tribulus terrestris, 4.5 parts of Eriocaulon buergerianum, 2.5 parts of Equisetum hyemale, 6.5 parts of Salvia miltiorrhiza, 6.5 parts of Paeonia lactiflora, 4.5 parts of Polygonum cuspidatum, 3 parts of Cynanchum paniculatum, 4.5 parts of Ligusticum chuanxiong, and 2 parts of Pueraria lobata.

4. A method for preparing a traditional Chinese medicine composition according to any one of claims 1 to 3, characterized in that, include: Weigh out the following medicinal slices according to the prescription ratio: Astragalus complanatus, Tribulus terrestris, Eriocaulon buergerianum, Equisetum hyemale, Salvia miltiorrhiza, Paeonia lactiflora, Polygonum cuspidatum, Cynanchum paniculatum, Ligusticum chuanxiong, and Pueraria lobata. Add 10 times the amount of water and decoct at 95-100℃ for 60 minutes. Filter the solution. Add 8 times the amount of water to the residue and decoct at 90-95℃ for 30 minutes. Filter the solution again. Combine the two filtrates and concentrate under reduced pressure to a relative density of 1.20±0.05 (60℃). Dry the concentrate under reduced pressure at 50-70℃ and pulverize it through a 60-100 mesh sieve to obtain a dry extract powder. Mix the dry extract powder with pharmaceutically acceptable excipients and granulate it using dry granulation or wet granulation processes. Alternatively, add microcrystalline cellulose and magnesium stearate to compress it into tablets or fill it into empty capsule shells to make capsules.

5. The preparation method according to claim 4, characterized in that, The vacuum concentration process uses a double-effect concentrator, with the vacuum degree maintained at -0.08 to -0.09 MPa; the vacuum drying process uses a vacuum drying oven, with the vacuum degree not lower than -0.09 MPa, and the drying endpoint is determined by the moisture content of the dry powder being no more than 8.0% as detected by a moisture analyzer.

6. The preparation method according to claim 4, characterized in that, When preparing granules, dry extract powder is mixed with dextrin and sucrose powder in a mass ratio of 1:1:

1. An 8% polyvinylpyrrolidone ethanol solution is added as a binder, and the mixture is stirred to form a soft mass. The mass is then passed through a 16-mesh sieve to form wet granules, which are dried at 60°C for 2 hours. After granulation, the granules are packaged into bags containing 6g of raw medicinal material.

7. The preparation method according to claim 4, characterized in that, When preparing tablets, dry extract powder and microcrystalline cellulose are mixed at a mass ratio of 1:0.

8. Sodium carboxymethyl starch, accounting for 2% of the total material mass, is added as a disintegrant, and magnesium stearate, accounting for 0.5% of the total material mass, is added as a lubricant. After mixing evenly, the mixture is compressed into tablets, each containing 1.5g of raw drug.

8. The preparation method according to claim 4, characterized in that, When preparing capsules, take the dry extract powder and fill the capsules directly.

9. The use of a traditional Chinese medicine composition as described in any one of claims 1 to 3 in the preparation of a medicament for treating non-proliferative diabetic retinopathy, characterized in that, The non-proliferative diabetic retinopathy is a syndrome characterized by deficiency of liver and kidney and obstruction of collaterals. Its clinical manifestations include blurred vision, dry eyes, dizziness and tinnitus, soreness and weakness of the waist and knees, numbness of limbs, constipation, dark red tongue with little coating or ecchymosis, and thready and hesitant pulse.

10. The application according to claim 9, characterized in that, The traditional Chinese medicine composition is an oral preparation.

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