Traditional Chinese medicine composition for treating non-proliferative diabetic retinopathy and application thereof

Abstract

The invention discloses a traditional Chinese medicine composition for treating non-proliferative diabetic retinopathy and application of the traditional Chinese medicine composition. The traditional Chinese medicine composition provided by the invention is prepared from the following medicinal materials in parts by weight: rhizoma polygonati, radix astragali, radix salviae miltiorrhizae, radix rehmanniae, semen cassiae, cassia twig, pollen typhae and flos eriocauli. The traditional Chinese medicine composition is scientific and reasonable in compatibility, rich in raw materials, convenient to take and good in effect, has the effects of tonifying qi, warming yang and promoting blood circulation to remove meridian obstruction together, can be effectively used for treating NPDR patients, is remarkable in curative effect, and is an innovation of NPDR treatment medicines.

Description

Technical Field

[0001] The present invention relates to the technical field of traditional Chinese medicines, and in particular to a traditional Chinese medicine composition for treating non-proliferative diabetic retinopathy and application thereof. Background Art

[0002] Non-proliferative diabetic retinopathy (NPDR) is the early stage of retinal microvascular damage caused by diabetes, manifesting as microaneurysms, hemorrhages, and hard exudates. NPDR is the most common eye complication of diabetes. Chronic high blood sugar levels damage the tiny retinal blood vessels, leading to leakage, occlusion, or abnormal dilation. The severity of the disease is categorized into three stages: mild, moderate, and severe. Severe NPDR can progress to proliferative retinopathy (PDR), increasing the risk of blindness. Currently, commonly used Western medicine treatments include calcium dobesilate, but these are generally ineffective.

[0003] According to Traditional Chinese Medicine, the early and middle stages of diabetes manifest as fullness and internal heat, which damages Yin and depletes Qi, impairing the vital energy of the internal organs. In the middle and late stages, the liver, spleen, and kidneys are often deficient. The eyes, where numerous small collaterals run, are prone to blood stasis. Poor blood sugar control, combined with collateral stasis, leads to this disease. Collateral stasis, in turn, transforms into heat, which forces blood circulation and causes bleeding. Therefore, this disease is characterized by Qi and Yin deficiency as the root cause and collateral stasis as the symptom. The syndrome is characterized by deficiency in the root and excess in the symptoms. The disease is located in the eyes, with the spleen at its root, involving both the liver and kidneys. The pathogenesis is due to deficiency, blood stasis, and collateral obstruction. Treatment involves tonifying Qi, nourishing Yin, and promoting blood circulation and unblocking the collaterals.

[0004] CN116139211A discloses a Chinese medicine composition for treating non-proliferative diabetic retinopathy and its use. The raw materials of the Chinese medicine composition include astragalus root, cinnamon twig, wolfberry fruit, coix seed, and raw pollen. This Chinese medicine composition has the effects of invigorating qi and warming yang, promoting blood circulation and unblocking collaterals, and is effective in treating non-proliferative diabetic retinopathy, with efficacy in delaying retinopathy, fundus microaneurysms, and fundus hemorrhages. However, this Chinese medicine composition has drawbacks such as unclear long-term efficacy for patients with non-proliferative diabetic retinopathy, inability to reduce the severity of retinopathy, and ineffectiveness in significantly improving blurred vision.

[0005] In view of this, the present invention is proposed. Summary of the Invention

[0006] The purpose of the present invention is to provide a traditional Chinese medicine composition for treating non-proliferative diabetic retinopathy (NPDR), which has unique advantages in improving vision, delaying the occurrence and development of DR, promoting improvement of the fundus with pathological changes, improving the overall condition of the patient, and improving the quality of life of the patient.

[0007] In order to achieve the above object, the technical solution adopted by the present invention is as follows: The present invention provides a traditional Chinese medicine composition, comprising the following medicinal ingredients in parts by weight: 9-60 parts by weight of polygonatum, 3-120 parts by weight of astragalus, 9-60 parts by weight of salvia miltiorrhiza, 10-30 parts by weight of raw rehmannia, 9-30 parts by weight of cassia seed, 3-30 parts by weight of cinnamon twig, 3-30 parts by weight of raw pollen, and 3-30 parts by weight of coix seed.

[0008] In a specific embodiment of the present invention, the traditional Chinese medicine composition comprises the following medicinal ingredients in parts by weight: 15-16g of polygonatum, 15-16g of astragalus, 12-13g of salvia miltiorrhiza, 12-13g of raw rehmannia, 15-16g of cassia seed, 6-7g of cinnamon twig, 9-10g of raw pollen, and 9-10g of coix seed.

[0009] The present invention also provides a traditional Chinese medicine extract, which is obtained by extracting the following medicinal ingredients in parts by weight: 9-60 parts by weight of polygonatum, 3-120 parts by weight of astragalus, 9-60 parts by weight of salvia miltiorrhiza, 10-30 parts by weight of raw rehmannia, 9-30 parts by weight of cassia seed, 3-30 parts by weight of cinnamon twig, 3-30 parts by weight of raw pollen, and 3-30 parts by weight of coix seed.

[0010] In a specific embodiment of the present invention, the Chinese medicine extract is obtained by extracting the following medicinal ingredients in parts by weight: 15-16g of polygonatum, 15-16g of astragalus, 12-13g of salvia miltiorrhiza, 12-13g of raw rehmannia, 15-16g of cassia seed, 6-7g of cinnamon twig, 9-10g of raw pollen, and 9-10g of coix seed.

[0011] The extraction is carried out according to the following operation: decocting each medicinal ingredient in water and combining the decoctions to obtain the product.

[0012] In a specific embodiment of the present invention, the preparation of the Chinese herbal extract is carried out according to the following operation: soak each medicinal ingredient in cold water for 30-35 minutes, add water to cover the medicinal ingredient by 2-3 cm, boil the first decoction over high heat (high heat), and then keep boiling over low heat (low heat) for 25-35 minutes, until 200 ml of the medicinal liquid remains, pour it out; add water again for the second decoction, just enough to soak the medicinal surface, boil over high heat, and then keep boiling over low heat (low heat) for 25-35 minutes, until 200 ml of the medicinal liquid remains, pour it out, and mix the two decoctions to obtain the product.

[0013] The present invention also provides a traditional Chinese medicine preparation, which comprises the above-mentioned traditional Chinese medicine composition or the above-mentioned traditional Chinese medicine extract.

[0014] The dosage form of the Chinese medicine preparation is decoction, granules, capsules, tablets, powders, pills or oral liquid.

[0015] The present invention also provides the use of the above-mentioned traditional Chinese medicine composition, the above-mentioned traditional Chinese medicine extract or the above-mentioned traditional Chinese medicine preparation in the preparation of a medicine for treating non-proliferative diabetic retinopathy.

[0016] The non-proliferative diabetic retinopathy is a disease caused by type 2 diabetes.

[0017] The present invention comprises the following prescriptions: the polygonatum in the prescription nourishes qi and yin, enters the spleen and kidney meridians, strengthens the spleen and tonifies the kidney, nourishes the yin of the spleen and kidney, and is used as the main medicine; the astragalus is a holy medicine for nourishing qi, nourishes qi and raises yang, and assists the polygonatum to strengthen the qi-tonifying effect, and is the minister medicine; the salvia miltiorrhiza can promote blood circulation and remove blood stasis, dredge blood vessels, and the raw rehmannia root clears heat and cools blood, promotes the production of body fluid and moistens dryness, which can both nourish yin and clear the heat of blood stasis. The two are combined with the polygonatum to promote blood circulation and remove blood stasis while nourishing the body, and are both minister medicines; the raw pollen can promote blood circulation and is flat in nature and taste, and can strengthen the minister medicine's power of promoting blood circulation in the collaterals while preventing bleeding due to excessive blood circulation; the cassia seed improves eyesight and improves the patient's vision, and the raw pollen can serve as an adjuvant medicine together with the raw pollen; the cinnamon twig is warm in nature and can promote blood circulation and dredge the menstruation, while resisting many cold and cool medicines in the prescription, and is the adjuvant medicine; the herb scoparia improves eyesight and removes cataracts, mainly enters the liver meridian, guides all medicines into the eyes, strengthens the effect of the prescription on the eyes, makes the function specific and effective, and is the meridian-guiding medicine. The combination of these medicines can replenish qi and nourish yin, promote blood circulation and dredge collaterals, and is used to treat the syndrome of deficiency, blood stasis and obstruction of collaterals in non-proliferative diabetic retinopathy.

[0018] Compared with the prior art, the present invention has the following beneficial effects: The invention has scientific and reasonable compatibility, abundant raw materials, convenient administration, good effect, and can achieve the effects of invigorating qi and warming yang, promoting blood circulation and unblocking collaterals. It can be effectively used for treating patients with NPDR, has remarkable efficacy, and is an innovation in the treatment of NPDR. DETAILED DESCRIPTION

[0019] The present invention will be further described below with reference to specific examples, but the present invention is not limited to the following examples.

[0020] Unless otherwise specified, the experimental methods used in the following examples are conventional methods.

[0021] Unless otherwise specified, the reagents, materials, instruments, etc. used in the following examples can be obtained from commercial sources.

[0022] Example 1, Chinese medicine composition This embodiment provides a traditional Chinese medicine composition, the composition of which is as follows: 15g of polygonatum, 15g of astragalus, 12g of salvia miltiorrhiza, 12g of raw rehmannia, 15g of cassia seed, 6g of cinnamon twig, 9g of raw pollen, and 9g of coix seed.

[0023] Example 2, decoction The Chinese medicine composition described in Example 1 was prepared into a decoction. The specific steps were as follows: the raw materials were taken according to the above prescription, decocted with water twice, each time for 1 hour, filtered, and the decoctions were combined to obtain the decoction.

[0024] Example 3, granules The Chinese medicine composition described in Example 1 is made into granules. The specific operation steps are as follows: the raw materials are taken according to the above prescription, and granules are made according to the conventional granulation process.

[0025] Experimental content 1 Study Objectives The efficacy of the Chinese medicine composition prepared in Example 1 on NPDR patients in the real world was evaluated.

[0026] 2 Research design This study adopted a prospective cohort study design of real-world research.

[0027] 3 Research subjects 3.1 Sample size Because there is no unified standard for calculating sample sizes in real-world studies, relevant literature shows that sample sizes in real-world studies are generally large. The sample size of this study was 500, including 150 in the exposed group and 350 in the non-exposed group.

[0028] 3.2 Diagnostic criteria (1) Have a clear history of type 2 diabetes; (2) The earliest visible retinal clinical manifestations in diabetic patients include microaneurysms and hemorrhages. Vascular changes can develop into retinal capillary nonperfusion, leading to clinical features such as increased number of hemorrhages, cotton-wool spots, and abnormalities of intraretinal microvessels. Continuous nonperfusion can eventually lead to occlusion and pathological proliferation of retinal blood vessels, manifesting as new blood vessels in the optic disc or other parts of the retina. During the course of NPDR, increased permeability of the vascular wall leads to retinal thickening (edema). Macular edema, macular capillary nonperfusion, vitreous hemorrhage, or tractional retinal detachment cause decreased vision.

[0029] 3.3 Inclusion criteria (1) Meet the diagnostic criteria for DR and the lesion is in the non-proliferative stage; (2) Age 30-70 years old.

[0030] Note: DR patients can be observed if one eye meets the inclusion criteria. If both eyes meet the inclusion criteria, please record them separately and use one eye for efficacy evaluation. The selection of the eye should refer to the following principles: when the fundus conditions of the two eyes are at different clinical stages, the more serious eye should be selected as the observation eye; when the fundus conditions of the two eyes are at the same clinical stage, the eye that cooperates better with clinical operation should be selected as the observation eye.

[0031] 3.4 Exclusion criteria (1) Other ophthalmic diseases not classified as DR, such as non-diabetic retinopathy, uveitis, retinal detachment, optic nerve disease, and high myopia with fundus lesions; (2) Meet the diagnostic criteria for DR, but the lesion is at the proliferative stage; (3) Type 1 diabetic retinopathy.

[0032] 4 Exposure factors and treatment options 4.1 Exposure factors The exposure factor of this study was the traditional Chinese medicine prescription prepared in Example 1.

[0033] 4.2 Exposure Based on clinical experience and expert consensus, the degree of exposure to traditional Chinese medicine is divided into high exposure, medium exposure, and low exposure.

[0034] High exposure group: taking the Chinese herbal composition for 12 months per year.

[0035] Medium exposure group: taking the Chinese herbal composition for 5-12 months per year.

[0036] Low exposure group: taking Chinese herbal compositions for less than 5 months per year.

[0037] 5. Efficacy and safety evaluation 5.1 Main efficacy evaluation indicators Changes in the severity of retinal microvascular disease (according to the DR severity grading standard). At each follow-up visit, patients underwent an ophthalmological examination as specified in the protocol. The DR stage of the patient was also recorded. The severity of retinal microvascular disease was categorized as worsening, unchanged, or improved based on the changes before and after treatment (none, mild non-proliferative stage, moderate non-proliferative stage, severe non-proliferative stage, and proliferative stage). Changes in the severity of retinal microvascular disease before and after treatment were evaluated, and the rates of reduction and worsening of retinal microvascular disease were compared between the two groups.

[0038] Aggravation refers to the progression of DR stage relative to the baseline or the stage remains unchanged but fundus indicators (microaneurysms, hemorrhage, exudation, etc.) worsen; Remission refers to the DR stage being relieved or the stage being unchanged but the fundus indicators (microaneurysm, hemorrhage, exudation, etc.) being reduced relative to the baseline; Unchanged means that both DR stage and fundus indexes remain unchanged compared with the baseline.

[0039] 5.2 Secondary efficacy evaluation indicators (1) Fundus examination showed retinal microvascular disease, microangiopathy, hemorrhage, and exudation: Compare the changes in retinal microvascular disease, microangiopathy, hemorrhage, and exudation in the patients' fundus at the end of the study and at the baseline.

[0040] (2) Macular edema degree: Compare the changes in the degree of macular edema of patients at the end of the study and at baseline.

[0041] Note: (Developed with reference to the "Guidelines for Clinical Research of New Chinese Medicines for the Treatment of Diabetic Retinopathy" in the "Guidelines for Clinical Research of New Chinese Medicines" published by China Medical Science and Technology Press, first edition May 2002) For patients with macular edema, the following aspects were evaluated: the shortest distance from the edge of the edema to the fovea; and the retinal thickness of the macular area.

[0042] The measured values ​​of the above two indicators of macular edema before and after taking the medicine were analyzed.

[0043] (3) Visual acuity: Compare the changes in the patient's best corrected visual acuity at the end of the study and at baseline.

[0044] Note: This study was developed with reference to the "Guiding Principles for Clinical Research of New Traditional Chinese Medicines for the Treatment of Diabetic Retinopathy" in the "Guiding Principles for Clinical Research of New Traditional Chinese Medicines," first edition published by China Medical Science and Technology Press in May 2002. Changes in best-corrected visual acuity before and after medication were analyzed using the EDTRS international visual acuity chart.

[0045] (4) Blood glucose: Compare the changes in HbA1c and FBG values ​​at the end of the study and at the baseline.

[0046] (5) Blood pressure: Compare the changes in patients' systolic and diastolic blood pressure at the end of the study with those at baseline. (5) Blood lipids: Compare the changes in CHO, TG, HDL, and LDL at the end of the study and at baseline (7) Incidence of endpoint events: This study will also evaluate the number of people entering the retinopathy endpoint event and the incidence rate. The specific endpoint events are as follows: ① SAEs that are so severe that the study cannot be continued; ② Diabetic retinopathy enters the proliferative stage; (8) Clinical symptoms: Evaluate the changes in clinical symptoms at the end of the study and at baseline.

[0047] 7. Results 7.1 Case inclusion and follow-up A total of 543 subjects were enrolled in this study, including 97 in the exposed group and 446 in the unexposed group. Complete evaluation criteria were achieved in 221 and 450 subjects at 18 and 12 months of follow-up, respectively. The minimum follow-up was 6 months. The main reason for dropout in both groups was poor patient compliance.

[0048] Table 1 Case inclusion and follow-up

[0049] 7.2 Primary Efficacy Evaluation Results 7.2.1 Changes in DR Severity (12-month Follow-up) Subjects followed up for 12 months were analyzed. The rates of DR worsening, unchanged, and remission were compared between the two groups, using the change in DR severity from baseline as the evaluation indicator. Aggravation refers to progression of DR stage or unchanged stage with worsening of fundus parameters (such as microaneurysms, hemorrhages, and exudates) relative to baseline; remission refers to remission of DR stage or unchanged stage with reduced fundus parameters (such as microaneurysms, hemorrhages, and exudates) relative to baseline; and no remission refers to no remission of both DR stage and fundus parameters relative to baseline. Ninety-three subjects were included in the exposed group and 204 in the unexposed group. In the exposed group, DR remission occurred in 31 patients (33.1%), no remission occurred in 51 patients (54.8%), and progression occurred in 11 patients (11.8%). In the unexposed group, DR remission occurred in 39 patients (19.1%), no remission occurred in 103 patients (50.5%), and progression occurred in 62 patients (30.4%). There was a statistically significant difference in DR remission rate (P=0.007) and progression rate between the two groups (P=0.001).

[0050] Table 2 Changes in DR severity (12-month follow-up)

[0051] 7.2.2 Changes in DR at Different Exposure Levels (12-month Follow-up) Exposure groups were divided into high, medium, and low exposure groups based on the degree of Chinese medicine use. The remission, stability, and exacerbation rates of DR were compared among the different groups. There were 47 patients in the high-exposure group, 28 in the medium-exposure group, 18 in the low-exposure group, and 204 in the non-exposure group. In the high-exposure group, DR was resolved in 20 patients (42.6%), remained unchanged in 25 patients (53.2%), and progressed in 2 patients (4.3%). In the medium-exposure group, DR was resolved in 7 patients (25.0%), remained unchanged in 18 patients (64.3%), and progressed in 3 patients (10.7%). In the low-exposure group, DR was resolved in 4 patients (22.2%), remained unchanged in 8 patients (44.4%), and progressed in 6 patients (33.3%). In the non-exposure group, DR was resolved in 39 patients (19.1%), remained unchanged in 103 patients (50.5%), and progressed in 62 patients (30.4%). There were statistically significant differences in the remission rate (P = 0.008) and exacerbation rate (P < 0.001) among the different groups.

[0052] Table 3 Changes in DR at different exposure levels (12-month follow-up)

[0053] 7.3 Secondary Efficacy Evaluation Results Comparison of secondary efficacy indicators between the 12-month follow-up and baseline revealed that the exposed group had statistically significant differences in microaneurysms, bleeding, exudation, blurred vision, and fasting blood glucose compared with baseline (P < 0.05). There were also statistically significant differences in exudation, microvascular abnormalities, and blurred vision in the non-exposed group (P < 0.05).

[0054] Table 4 Results of secondary efficacy evaluation

[0055] 8. Conclusion 1. Treatment with the Chinese medicine composition provided by the present invention can promote the relief of NPDR and delay the progression of NPDR, and the effect becomes gradually more obvious as the medication time increases.

[0056] 2. Treatment with the Chinese medicine composition provided by the present invention can improve the symptoms of fundus hemorrhage, exudation and blurred vision in NPDR patients, and the effect becomes gradually more obvious as the medication time increases.

[0057] Comparative Example The formula disclosed in CN116139211A is as follows: 30g of Astragalus, 9g of Cinnamon Twig, 9g of Wolfberry Fruit, 9g of Coix Seed Herba, and 9g of Raw Pollen.

[0058] Comparative testing Comparing the formula of Example 1 with the comparative example, the results are as follows: 1. Comparison of therapeutic effects on non-proliferative diabetic retinopathy The prescription study of CN116139211A lasted 12 months and included 112 patients. The prescription only slowed the progression of retinopathy. In contrast, the clinical study of the prescription of Example 1 included 543 patients, with the longest follow-up period of 18 months. Long-term follow-up results showed that the DR remission rate in the exposed group was 33.1%, and the progression rate was 11.8%; while the DR remission rate in the unexposed group was 19.1%, and the progression rate was 30.4%, demonstrating the long-term efficacy of the prescription.

[0059] Conclusion: The prescription of the present invention has a clear long-term effect on patients with non-proliferative diabetic retinopathy, with a large sample size. It not only delays the progression of retinopathy, but also alleviates the severity of retinopathy.

[0060] 2. Comparison of patients' improvement in blurred vision symptoms The formula of CN116139211A failed to improve the blurred vision symptoms of patients. However, the above clinical study results showed that compared with the baseline (40.9%), the proportion of patients who still had blurred vision symptoms after taking the formula of Example 1 decreased (30.1%).

[0061] Conclusion: The prescription of the present invention can also improve patients' blurred vision symptoms.

[0062] In summary, compared with the prescription of CN116139211A, the prescription of the present invention has been improved in terms of medicinal taste, pathogenesis and treatment method, and has multiple effects.

[0063] Although the present invention has been described in detail above using general descriptions and specific embodiments, it will be apparent to those skilled in the art that modifications and improvements may be made based on the present invention. Therefore, such modifications and improvements, which do not depart from the spirit of the present invention, are intended to be within the scope of protection claimed herein.

Claims

1. A Chinese medicine composition, characterized in that The invention comprises the following medicinal ingredients in parts by weight: 9-30 parts by weight of polygonatum, 9-30 parts by weight of astragalus, 9-20 parts by weight of salvia miltiorrhiza, 10-27 parts by weight of raw rehmannia, 9-27 parts by weight of cassia seed, 3-27 parts by weight of cinnamon twig, 5-20 parts by weight of raw pollen, and 5-20 parts by weight of coix seed.

2. The Chinese medicine composition according to claim 1, characterized in that The invention comprises the following medicinal ingredients in parts by weight: 15-16g of polygonatum, 15-16g of astragalus, 12-13g of salvia miltiorrhiza, 12-13g of raw rehmannia, 15-16g of cassia seed, 6-7g of cinnamon twig, 9-10g of raw pollen, and 9-10g of coix seed.

3. A Chinese medicine extract, characterized in that The invention is obtained by extracting the following medicinal ingredients in parts by weight: 9-30 parts by weight of polygonatum, 9-30 parts by weight of astragalus, 9-20 parts by weight of salvia miltiorrhiza, 10-27 parts by weight of raw rehmannia, 9-27 parts by weight of cassia seed, 3-27 parts by weight of cinnamon twig, 5-20 parts by weight of raw pollen and 5-20 parts by weight of coix seed.

4. The Chinese medicine extract according to claim 3, characterized in that The extraction is carried out according to the following operation: decocting each medicinal ingredient in water and combining the decoctions to obtain the product.

5. The Chinese medicine extract according to claim 3, characterized in that The invention is obtained by extracting the following medicinal ingredients in parts by weight: 15-16g of polygonatum, 15-16g of astragalus, 12-13g of salvia miltiorrhiza, 12-13g of rehmannia glutinosa, 15-16g of cassia seed, 6-7g of cinnamon twig, 9-10g of raw pollen and 9-10g of coix seed.

6. A Chinese medicine preparation, characterized in that The traditional Chinese medicine preparation comprises the traditional Chinese medicine composition according to claim 1 or 2 or the traditional Chinese medicine extract according to any one of claims 3 to 5.

7. The Chinese medicine preparation according to claim 6, characterized in that The dosage form of the traditional Chinese medicine preparation is decoction, granules, capsules, tablets, powders, pills or oral liquid.

8. Use of the Chinese medicine composition according to claim 1 or 2, the Chinese medicine extract according to any one of claims 3 to 5, or the Chinese medicine preparation according to claim 6 or 7 in the preparation of a medicament for treating non-proliferative diabetic retinopathy.

9. The use according to claim 8, characterized in that The non-proliferative diabetic retinopathy is a disease caused by type 2 diabetes.

Images