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CN-122005589-A - Traditional Chinese medicine monomer composition derived from chrysanthemum plants for treating diabetic retinopathy and preparation method and application thereof

CN122005589ACN 122005589 ACN122005589 ACN 122005589ACN-122005589-A

Abstract

The invention discloses a traditional Chinese medicine monomer composition derived from chrysanthemum plants for treating diabetic retinopathy, and a preparation method and application thereof. The traditional Chinese medicine monomer composition prepared from chrysanthemum plants serving as raw materials is high in safety, small in side effect, clear in components and composed according to a specific proportion, and compared with ethanol extracts, the traditional Chinese medicine monomer composition is more remarkable in curative effect in treating diabetic retinopathy, can improve pathological states of diabetic retinopathy from multiple targets and multiple ways, can inhibit physical quality increase caused by high sugar, reduce blood sugar level, improve retinal tissue structure damage, restore retinal tissue thickness, inhibit retinal apoptosis and inflammatory reaction, reduce HIF-1 alpha and VEGF protein expression level in retinal tissues, delay disease progression, and provides scientific basis and technical support for development of novel therapeutic drugs for diabetic retinopathy, and has important clinical significance and market application prospect.

Inventors

  • CHANG XIANGWEI
  • CHEN CHUNXI
  • CHEN XIYA
  • LI SONG
  • WU DELING
  • HAN LAN
  • Ou Jinmei
  • BAO TAOTAO

Assignees

  • 安徽中医药大学

Dates

Publication Date
20260512
Application Date
20260225

Claims (10)

  1. 1.A traditional Chinese medicine monomer composition for treating diabetic retinopathy from chrysanthemum plants is characterized by comprising chlorogenic acid, cryptochlorogenic acid, quercetin-3, 7-di-O-beta-D-glucoside, luteolin-7, 4' -di-O-beta-D-glucoside, tuberonic acid glucoside, apigenin-6, 8-di-C-glucoside, 1, 3-O-dicaffeoylquinic acid, apigenin-6-C-glucoside-8-C-arabinoside, eriodictyol-7-O-beta-D-glucoside, isoquercitrin, luteolin, isochlorogenic acid B, 1, 5-O-dicaffeoylquinic acid, isochlorogenic acid A, apigenin-7-O-beta-D-glucoside, isochlorogenic acid C, geraniin-7-O-beta-D-glucoside, geraniin-7-O-6-malonyl glucoside, farnesyl glucoside and farnesoid-7-O-beta-D-glucoside according to a mass ratio of 3.88~6.99∶78.77~154.32∶73.54~125.46∶53.94~90.27∶49.93~80.96∶264.90~450.42∶53.37~107.93∶50.61~89.82∶4.52~8.15∶2.56~4.47∶25.45~44.12∶9.69~17.25∶29.82~64.36∶8.43~13.55∶5.80~14.40∶0.95~3.27∶3.45~5.71∶269.42~414.94∶3170.57~5685.61∶1.
  2. 2. The traditional Chinese medicine monomer composition according to claim 1, wherein the traditional Chinese medicine monomer composition consists of chlorogenic acid, cryptochlorogenic acid, quercetin-3, 7-di-O-beta-D-glucoside, luteolin-7, 4' -di-O-beta-D-glucoside, tuberonic acid glucoside, apigenin-6, 8-di-C-glucoside, 1, 3-O-dicaffeoylquinic acid, apigenin-6-C-glucoside-8-C-arabinoside, eriodictyol-7-O-beta-D-glucoside, isoquercitrin, luteolin, isochlorogenic acid B, 1, 5-O-dicaffeoylquinic acid, isochlorogenic acid A, apigenin-7-O-beta-D-glucoside, isochlorogenic acid C, geranin-7-O-beta-D-glucoside, lignin-7-O-6-malonyl glucoside, farnesoid-7-O-beta-D-glucoside and daphnetin.
  3. 3. The traditional Chinese medicine monomer composition according to claim 2, wherein the traditional Chinese medicine monomer composition consists of chlorogenic acid, cryptochlorogenic acid, quercetin-3, 7-di-O-beta-D-glucoside, luteolin-7, 4 '-di-O-beta-D-glucoside, tuberonic acid glucoside, apigenin-6, 8-di-C-glucoside, 1, 3-O-dicaffeoyl quininic acid, apigenin-6-C-glucoside, holonol-7-O-beta-D-glucoside, isoquercitrin, luteolin-B, isoculoside B,1, 5-O-beta-D-glucoside, luteolin-7, 4' -di-O-beta-D-glucoside, tuberonic acid glucoside, apigenin-6, 8-di-C-glucoside, 1, 3-O-dicaffeoyl quinic acid, apigenin-6-C-glucoside-8-C-arabinoside, holonol-7-beta-D-glucoside, isoquercitrin, luteolin-B, 1, 5-O-beta-D-glucoside, luteolin-7, D-beta-D-glucoside, luteolin-C-glucoside, luteolin-7, D-beta-D-glucoside and luteolin-C-arabinoside according to the mass ratio of 5.1:98.8:8:8.8:8:5:5.4: 3512.1:1.
  4. 4. A method for preparing the traditional Chinese medicine monomer composition according to any one of claims 1 to 3, comprising the following steps: (1) Adding chrysanthemum plant raw materials into an extraction solvent for heating reflux extraction, filtering and concentrating an extracting solution, adding a proper amount of distilled water, and carrying out suction filtration to obtain a sample loading solution; (2) Adsorbing the sample liquid by macroporous resin, eluting with distilled water to remove impurities, eluting with eluting solvent, collecting eluate, concentrating, and drying to obtain total flavone chemical site; (3) Separating from mouse eyeball to obtain crystalline lens, adding PBS buffer solution, homogenizing, collecting supernatant, sequentially regulating the concentration of ammonium sulfate solution in the supernatant to obtain crude enzyme extract, and dialyzing to obtain refined enzyme solution; (4) Mixing the total flavone chemical part solution with the refined enzyme solution, incubating for 20-40 min in a 37 ℃ water bath, centrifuging, adding PBS buffer solution to remove compounds not combined with enzyme, adding 50% -80% methanol solution, incubating at room temperature, and centrifuging to obtain the traditional Chinese medicine monomer composition.
  5. 5. The preparation method of the traditional Chinese medicine monomer composition according to claim 4, wherein in the step (1), the chrysanthemum plant raw material comprises chrysanthemum inflorescences, chrysanthemum stems and leaves or chrysanthemum roots, the extraction solvent is distilled water or 30% -85% ethanol solution, the feed-liquid ratio is 1:10-20 g/mL, the extraction time is 1-3 h, and the extraction times are 1-2 times.
  6. 6. The method for preparing a Chinese medicinal monomer composition according to claim 4, wherein in the step (2), The mass concentration of the sample loading liquid is 25-125 mg/mL, and/or The volume of the sample loading liquid is 10-110 mL, and/or The macroporous resin is any one of AB-8, NKA-9, HPD-500, DM-130 or DM-301, and/or The volume flow rate of the sample loading liquid is 0.5-2.0 mL/min, and/or The column volume of the distilled water is 1-2 BV, and/or The eluting solvent is 60% -80% ethanol solution and/or The volume of the eluting solvent is 2-4 BV, and/or In the step (4), the volume ratio of the total flavonoid part solution to the refined enzyme solution is 1:1-3, and/or The concentration of the total flavonoid partial solution is 0.5-2 mg/mL, and/or The concentration of the refined enzyme solution is 1-3.5 mg/mL.
  7. 7. An application of the traditional Chinese medicine monomer composition according to any one of claims 1-3 in preparing a medicament for treating diabetic retinopathy.
  8. 8. The use according to claim 7, wherein the herbal monomer composition is useful in the preparation of a medicament for treating diabetic retinopathy by inhibiting the growth of high glucose-induced mass, reducing blood glucose levels, improving retinal tissue structure damage, restoring retinal tissue thickness, inhibiting retinal apoptosis and inflammatory responses, and reducing HIF-1 a and VEGF protein expression levels in retinal tissue.
  9. 9. A medicament for treating diabetic retinopathy, which is characterized by comprising an effective amount of the traditional Chinese medicine monomer composition according to any one of claims 1-3 and pharmaceutically acceptable auxiliary materials.
  10. 10. The medicament according to claim 9, wherein the dosage form of the medicament comprises any one of decoction, oral liquid, patch, tablet, granule, capsule, paste, pill, powder, pellet, injection or sustained-release preparation.

Description

Traditional Chinese medicine monomer composition derived from chrysanthemum plants for treating diabetic retinopathy and preparation method and application thereof Technical Field The invention belongs to the technical field of biological medicines, and particularly relates to a traditional Chinese medicine monomer composition derived from chrysanthemum plants for treating diabetic retinopathy, and a preparation method and application thereof. Background Diabetic retinopathy (Diabetic retinopathy, DR) is one of the leading causes of blindness and vision impairment, and the global DR patient is expected to increase from 1.03 million people in 2020 to 1.61 million people in 2045. Despite the increasing research directed to DR therapy, effective treatment of the disease in clinical practice remains challenging due to the complex pathogenesis of DR. At present, the main treatment modes of DR in clinic are divided into two major categories of drug treatment and surgical treatment. The medicine treatment mainly comprises a hypoglycemic medicine and an anti-VEGF medicine, wherein the hypoglycemic medicine is used for controlling basic blood sugar level to delay the development of DR, the anti-VEGF medicine (such as Abposite, bevacizumab and the like) is used for inhibiting abnormal neovascularization through intraocular injection to relieve fundus diseases, when DR is developed to an advanced stage, a patient needs to adopt operation treatment such as full retina laser photocoagulation, vitrectomy and the like, and disease control is realized by sealing leakage blood vessels, removing vitreous volume blood or resetting and separating retina. However, these treatments can result in side effects such as hypoglycemia, gastrointestinal discomfort, reduced renal function, and peripheral vision loss. The traditional Chinese medicine has obvious clinical curative effects in the aspects of delaying the progression of DR disease, reducing the occurrence rate of blindness and improving the life quality of patients, has the advantage of low toxicity, and becomes an important direction for developing new drugs for DR treatment in recent years. At present, most of traditional Chinese medicines used for DR treatment in clinic and research are single Chinese herbal medicine extracts or Chinese herbal medicine compound extracts, and although the traditional Chinese medicine extracts have a certain prevention and treatment effect on DR, the chemical components of the extracts are complex, specific action targets and molecular mechanisms of the extracts for treating DR are difficult to clearly explain, and the problems of difficult quality control, large batch-to-batch curative effect difference, low purity and the like exist, so that the wide application and further research and development of the extracts in clinic are limited. The flos Chrysanthemi is a dry head-like inflorescence of Compositae plant flos Chrysanthemi Chrysanthemum morifolium Ramat, is a bulk Chinese medicinal material with homology of medicine and food, and has effects of dispelling pathogenic wind and heat, suppressing hyperactive liver, improving eyesight, removing toxic substances, and relieving swelling. Modern researches have shown that chrysanthemum contains rich flavonoid, phenolic acid, volatile oil and other chemical components and has various pharmacological activities of resisting oxidation, resisting inflammation, inhibiting bacteria, reducing blood sugar, protecting liver and the like. The prior researches prove that the chemical components and pharmacological actions of the chrysanthemum stem leaves, the chrysanthemum roots and the chrysanthemum inflorescences are similar, and the chrysanthemum stem leaves, the chrysanthemum roots and the chrysanthemum inflorescences have the potential of development and utilization. However, at present, pharmacological researches on chrysanthemum mainly focus on the aspect of total flavone extracts, and no published literature or patent report on specific traditional Chinese medicine monomer compositions derived from chrysanthemum plants have therapeutic effects on diabetic retinopathy. Disclosure of Invention In view of the above, the invention aims to provide a traditional Chinese medicine monomer composition for treating diabetic retinopathy, which is derived from chrysanthemum plants, has definite components and scientific proportion, has definite curative effect for treating diabetic retinopathy and small side effect due to the synergistic effect of all monomer compounds, and provides scientific basis and technical support for the research and development of novel medicines for treating diabetic retinopathy. The invention is realized by the following technical scheme: In one aspect, the invention provides a traditional Chinese medicine monomer composition for treating diabetic retinopathy, which is derived from chrysanthemum plants and consists of chlorogenic acid, cryptochlorogenic acid, quercetin-3, 7-di-O