WO2022236790A1 - 短棒石斛、聚石斛和红牙刷石斛的提取物作为α-葡萄糖苷酶抑制剂的应用 - Google Patents

短棒石斛、聚石斛和红牙刷石斛的提取物作为α-葡萄糖苷酶抑制剂的应用 Download PDF

Info

Publication number
WO2022236790A1
WO2022236790A1 PCT/CN2021/093731 CN2021093731W WO2022236790A1 WO 2022236790 A1 WO2022236790 A1 WO 2022236790A1 CN 2021093731 W CN2021093731 W CN 2021093731W WO 2022236790 A1 WO2022236790 A1 WO 2022236790A1
Authority
WO
WIPO (PCT)
Prior art keywords
dendrobium
main component
extract
pentamethoxybibenzyl
cypripedin
Prior art date
Application number
PCT/CN2021/093731
Other languages
English (en)
French (fr)
Inventor
黄圣卓
梅文莉
杨理
魏艳梅
蔡彩虹
李薇
王雅丽
戴好富
Original Assignee
中国热带农业科学院热带生物技术研究所
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by 中国热带农业科学院热带生物技术研究所 filed Critical 中国热带农业科学院热带生物技术研究所
Priority to PCT/CN2021/093731 priority Critical patent/WO2022236790A1/zh
Publication of WO2022236790A1 publication Critical patent/WO2022236790A1/zh

Links

Images

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/075—Ethers or acetals
    • A61K31/085—Ethers or acetals having an ether linkage to aromatic ring nuclear carbon
    • A61K31/09—Ethers or acetals having an ether linkage to aromatic ring nuclear carbon having two or more such linkages
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/88—Liliopsida (monocotyledons)
    • A61K36/898—Orchidaceae (Orchid family)
    • A61K36/8984—Dendrobium
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
    • A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C41/00—Preparation of ethers; Preparation of compounds having groups, groups or groups
    • C07C41/01—Preparation of ethers
    • C07C41/34—Separation; Purification; Stabilisation; Use of additives
    • C07C41/36—Separation; Purification; Stabilisation; Use of additives by solid-liquid treatment; by chemisorption

Definitions

  • the invention relates to the field of medicine, in particular to the application of the extracts of dendrobium short rods, dendrobium polydense and red toothbrush dendrobium and their main component compounds as alpha-glucosidase inhibitors.
  • Diabetes is a group of metabolic diseases characterized by hyperglycemia. Hyperglycemia is caused by defective insulin secretion or impaired biological action, or both. Long-term high blood sugar leads to chronic damage and dysfunction of various tissues, especially the eyes, kidneys, heart, blood vessels, and nerves. ⁇ -glucosidase plays an important role in the process of food absorption and must be combined with it before food can be digested and absorbed.
  • the hypoglycemic mechanism of ⁇ -glucosidase inhibitors is to slow down the decomposition of starch into glucose by inhibiting ⁇ -glucosidase on the intestinal mucosa, reducing and delaying the absorption of glucose by the small intestine, so as to lower blood sugar and have a positive effect on postprandial
  • the effect of hyperglycemia is more obvious.
  • Glucosidase inhibitors do not stimulate insulin secretion, and they usually do not cause hypoglycemia when used alone, so they can help reduce blood sugar fluctuations. It can significantly reduce the probability of cardiovascular disease in diabetic patients, and the improvement effect on myocardial infarction is the most significant.
  • ⁇ -glucosidase inhibitors are mainly acarbose and voglibose.
  • abdominal distension, abdominal pain, diarrhea, nausea, and vomiting may still occur, and adverse reactions such as gastrointestinal spasm pain and intractable constipation may also occur.
  • the present invention provides the application of the extract and main component compound thereof of Dendrobium dendrobii, polydendrobium and red toothbrush Dendrobium as ⁇ -glucosidase inhibitors, so that said extract and compound have ⁇ -glucoside It has enzyme inhibitory activity, has a significant effect on lowering blood sugar, and has high safety and no toxic side effects.
  • the invention provides Dendrobium extract, the main component compounds of which include Chrysotobibenzyl, Gigantol, Chrysotoxine, 5-Hydroxy-3,4,3',4',5'-pentamethoxybibenzyl, Brittonin A, 4,5,4'-trihydroxy- One or more of 3,3'-dimethoxybibenzyl or Cypripedin.
  • the preparation method of the Dendrobium extract comprises: taking the Dendrobium dendrobium, drying and pulverizing, extracting 3 times with 2 times of ethanol, concentrating, extracting and degreasing 3 times with 1 times of petroleum ether, and adjusting the pH value to 9.0 ⁇ 10.0, filtered, extracted 3 times with 1 times ethyl acetate, concentrated to obtain the ethyl acetate fraction, and obtained the Dendrobium extract.
  • the Dendrobium candidum comprises one or more of Dendrobium brevifolia, Dendrobium polysense or Dendrobium red toothbrush.
  • the Dendrobium stems from plants Dendrobium capillipes Rchb.f. (scientific name: Dendrobium capillipes Rchb.f.), Poly Dendrobium (scientific name: Dendrobium lindleyi Stendel) and red toothbrush Dendrobium (scientific name: Dendrobium secundum (Blume) Lindl.) extraction and separation or by chemical synthesis.
  • the present invention also provides the application of the dendrobium extract or its main component compounds in the preparation of ⁇ -glucosidase inhibitors.
  • the main component compounds thereof include Chrysotobibenzyl, Gigantol, Chrysotoxine, 5-Hydroxy-3,4,3',4',5'-pentamethoxybibenzyl, Brittonin A, 4,5,4 One or more of '-trihydroxy-3,3'-dimethoxybibenzyl or Cypripedin.
  • the present invention also provides the application of the dendrobium extract or its main component compounds in the preparation of medicaments for preventing and/or treating diabetes.
  • the main component compounds thereof include Chrysotobibenzyl, Gigantol, Chrysotoxine, 5-Hydroxy-3,4,3',4',5'-pentamethoxybibenzyl, Brittonin A, 4,5,4 One or more of '-trihydroxy-3,3'-dimethoxybibenzyl or Cypripedin.
  • the present invention also provides ⁇ -glucosidase inhibitors, including the Dendrobium extract or its main component compounds; the main component compounds include Chrysotobibenzyl, Gigantol, Chrysotoxine, 5-Hydroxy-3,4,3', One or more of 4',5'-pentamethoxybibenzyl, Brittonin A, 4,5,4'-trihydroxy-3,3'-dimethoxybibenzyl or Cypripedin.
  • the main component compounds include Chrysotobibenzyl, Gigantol, Chrysotoxine, 5-Hydroxy-3,4,3', One or more of 4',5'-pentamethoxybibenzyl, Brittonin A, 4,5,4'-trihydroxy-3,3'-dimethoxybibenzyl or Cypripedin.
  • the present invention also provides a drug for preventing and/or treating diabetes, including the Dendrobium extract or its main component compounds; the main component compounds include Chrysotobibenzyl, Gigantol, Chrysotoxine, 5-Hydroxy-3,4,3' , one or more of 4',5'-pentamethoxybibenzyl, Brittonin A, 4,5,4'-trihydroxy-3,3'-dimethoxybibenzyl or Cypripedin, and pharmaceutically acceptable excipients.
  • the main component compounds include Chrysotobibenzyl, Gigantol, Chrysotoxine, 5-Hydroxy-3,4,3' , one or more of 4',5'-pentamethoxybibenzyl, Brittonin A, 4,5,4'-trihydroxy-3,3'-dimethoxybibenzyl or Cypripedin, and pharmaceutically acceptable excipients.
  • the dosage form of the drug includes water solvent or solid; the solid includes one or more of tablets, granules, capsules, powders, and pills.
  • the invention discloses the application of the extracts of dendrobium short rod, dendrobium poly and red toothbrush dendrobium and their main component compounds as alpha-glucosidase inhibitors.
  • the present invention utilizes the extract obtained by the plant extraction and separation method and its main components, which can effectively inhibit the activity of ⁇ -glucosidase, and has no toxic side effects and drug dependence on the human body, and has excellent drug efficacy in the experiment of inhibiting ⁇ -glucosidase activity.
  • it can be widely used in reducing postprandial hyperglycemia, reducing the incidence of cardiovascular complications, and intervening in the preparation of insulin-dependent or non-insulin-dependent oral hypoglycemic drugs.
  • Fig. 1 shows the phytochemical preparation process of three kinds of Dendrobium extracts and nine kinds of compounds.
  • the present invention discloses the application of the extracts of Dendrobium short rod, Dendrobium polydense and Dendrobium red toothbrush and their main component compounds as ⁇ -glucosidase inhibitors.
  • Those skilled in the art can learn from the content of this article and appropriately improve the process parameters to achieve.
  • all similar replacements and modifications are obvious to those skilled in the art, and they are all considered to be included in the present invention.
  • the method and application of the present invention have been described through preferred embodiments, and the relevant personnel can obviously make changes or appropriate changes and combinations to the method and application described herein without departing from the content, spirit and scope of the present invention to realize and Apply the technology of the present invention.
  • the object of the present invention is to provide the application of three kinds of dendrobium extracts and their main component compounds, so that the extracts and compounds have ⁇ -glucosidase inhibitory activity, have a significant effect of lowering blood sugar, and have high safety and no side effects .
  • the present invention provides the following technical solutions:
  • the ethyl acetate part is divided into A-F sections by silica gel column (200-300 mesh, petroleum ether: ethyl acetate 10:1, 5:1, 3:1, 2:1, 1:1 and 1:2) chromatography , Determine the location of the compound through the standard, and focus on separation.
  • the part where the compound is located is purified or crystallized after repeated chromatographic separation by ODS, MCI and normal phase silica gel, and the monomer compound is obtained by filtering the crystallization.
  • the compounds of the present invention can be prepared into various agricultural or clinical conventional preparations according to the conventional preparation methods in the art, for example, pharmaceutical preparations can be added to the dosage of the effective amount of the present invention.
  • Acceptable excipients (such as disintegrants, lubricants, binders, dispersants, etc.) are prepared into various oral medicaments, and the present invention is preferably made into tablets, granules, capsules, powders, pills or oral liquids.
  • auxiliary materials used in the preparation are also well known in the art, such as carboxymethyl Sodium starch, sucrose powder, honey, sesame oil, etc.
  • the extract and the main compound of the present invention have better drug activity than acarbose, and lower toxicity and residue than acarbose.
  • the compound of the present invention has obvious curative effect on reducing postprandial blood sugar in diabetic patients, and has no toxic side effect and drug dependence.
  • the present invention is safe and reliable, and can be used in medicine to reduce postprandial blood sugar for diabetic patients, and has no toxic side effects and drug dependence on the human body. Incidence of vascular complications, intervention preparation of insulin-dependent or non-insulin-dependent oral hypoglycemic agents.
  • the raw materials and reagents used can be purchased from the market.
  • the ethyl acetate part is divided into A-F sections by silica gel column (200-300 mesh, petroleum ether: ethyl acetate 10:1, 5:1, 3:1, 2:1, 1:1 and 1:2) chromatography , Determine the location of the compound through the standard, and focus on separation.
  • the part where the compound is located is purified or crystallized after repeated chromatographic separation by ODS, MCI and normal phase silica gel, and the monomer compound is obtained by filtering the crystallization.
  • Embodiment 2 prepares the capsule of compound described in the present invention
  • the extract or monomer compound provided in Example 1 of the present invention is first coarsely screened, and the maximum final concentration is generally 200 ⁇ M, which can be adjusted appropriately; if the IC50 value is measured, then dilute several Concentration can be detected by the same method. If it is a crude sample, generally the maximum final concentration is 200 ⁇ g/mL, which can be adjusted appropriately.
  • Preparation of the sample solution to be tested Take 450 ⁇ L of the prepared 0.2U/ml ⁇ -glucosidase solution in the EP tube, then add 45 ⁇ L of the solution to be tested, shake well, take 110 ⁇ L in a 96-well plate (4 times repeated ); (Negative and Blank: Take 450 ⁇ L prepared 0.2U/ml ⁇ -glucosidase solution in EP tube, then add 45 ⁇ L DMSO, shake well, take 110 ⁇ L solution in 96-well plate (repeat 4 times) ); place the 96-well plate at 37°C for 15 minutes, add 40 ⁇ L PNPG solution to the test group; (blank: add 40 ⁇ L PBS solution (0.1mol/L)); place the 96-well plate at 37°C for 15 minutes, The OD value of each well was detected at a wavelength of 405nm.
  • Inhibition rate (OD DMSO -OD sample )/(OD DMSO -OD PBS ) ⁇ 100%
  • Inhibition rate (OD DMSO - (OD sample - OD background )) / (OD DMSO - OD PBS ) ⁇ 100% (experimental group / positive control): 0.2U/mL ⁇ dissolved in 10 ⁇ L test sample solution + 100 ⁇ L PBS solution - Glycosidase solution + 40 ⁇ L of 2.5 mmol/L PNPG solution (OD sample ).
  • Blank 0.2 U/mL ⁇ -glucosidase solution dissolved in 10 ⁇ L DMSO solution + 100 ⁇ L PBS solution + 40 ⁇ L 0.1 mol/L PBS solution (OD PBS ).
  • Get Kunming kind of mouse give medicine of the present invention (extract and the powder in the compound capsule prepared by embodiment 3) by intragastric administration at 1g/kg, 1 day continuous administration 4 times, every interval 6h, then give normal diet, Pathological examinations were performed on various organs, and no organ lesions were found.
  • mice give the medicine of the present invention (the powder in the compound capsule prepared by embodiment 3) by intragastric administration of medium and large dose groups (1g/kg, 2g/kg), once a day, after 14 days of continuous administration, The body weight, heart function, liver function, kidney function, electrocardiogram and other indicators of the mice were measured, and the administration group was compared with the control group, and no obvious abnormalities were found. Pathological examination of the heart, liver, kidney, spleen, lung, stomach, duodenum, large intestine, small intestine, adrenal gland, and genital organs, compared with the control group, showed no obvious toxic changes. The above results show that the extracts and compounds of the present invention are safe and non-toxic, and can be used clinically.
  • Example 7 The extracts and compound preparations of the present invention have been clinically tested respectively
  • Combined medication group elderly patients with T2DM, 25 females and 21 males were randomly divided into the combined group.
  • Compound preparation (capsule of Example 1) 50 mg/time, 3 times/d. Continuous treatment for 3 months.
  • 2h blood glucose (2hPG), fasting blood glucose (FPG), and glycosylated hemoglobin (HbA1c) were checked after meals in the combined group.
  • the data used SPSS 22.0 statistical software, and the measurement data was Said, t test, count data with n (%) said, ⁇ 2 test.
  • the total effective rate of the combination group was 93.5% and that of the single group was 84.6% (P>0.05).
  • 2hPG, FPG, and HbA1c in the two groups decreased, and the combined group was lower than the single group.
  • the incidence of hypoglycemia in the combined group was 2.18% lower than that in the single group (19.6%), and the incidence of gastrointestinal reactions was 10.87% lower than that in the single group (28.26% (P ⁇ 0.05). (See Table 2 for the results)
  • T2DM patients Three kinds of extracts and seven kinds of compound capsules were used for clinical treatment of 46 diabetic patients (T2DM patients). The results showed that this drug, as an oral hypoglycemic drug, has a clear hypoglycemic effect on diabetic patients combined with insulin.

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Natural Medicines & Medicinal Plants (AREA)
  • Organic Chemistry (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Pharmacology & Pharmacy (AREA)
  • General Health & Medical Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Medicinal Chemistry (AREA)
  • Diabetes (AREA)
  • Engineering & Computer Science (AREA)
  • Epidemiology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Alternative & Traditional Medicine (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Obesity (AREA)
  • Hematology (AREA)
  • Endocrinology (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Biotechnology (AREA)
  • Botany (AREA)
  • Medical Informatics (AREA)
  • Microbiology (AREA)
  • Mycology (AREA)
  • Emergency Medicine (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)

Abstract

短棒石斛、聚石斛和红牙刷石斛的提取物及其主要成分化合物作为α-葡萄糖苷酶抑制剂的应用。短棒石斛、聚石斛和红牙刷石斛的提取物及其主要成分能够有效地抑制α-葡萄糖苷酶活性，应用于降低餐后高血糖，降低心血管并发症的发生率，用于制备胰岛素依赖型或非胰岛素依赖型口服降糖药。

Description

短棒石斛、聚石斛和红牙刷石斛的提取物作为α-葡萄糖苷酶抑制剂的应用 技术领域
本发明涉及医药领域，特别涉及短棒石斛、聚石斛和红牙刷石斛的提取物及其主要成分化合物作为α-葡萄糖苷酶抑制剂的应用。
背景技术
糖尿病是一组以高血糖为特征的代谢性疾病。高血糖则是由于胰岛素分泌缺陷或其生物作用受损，或两者兼有引起。长期存在的高血糖，导致各种组织，特别是眼、肾、心脏、血管、神经的慢性损害、功能障碍。α-葡萄糖苷酶在食物吸收过程中起着重要的作用，必须与之结合后，食物才能消化和吸收。α-葡萄糖苷酶抑制剂的降糖机制是，通过抑制肠黏膜上的α-葡萄糖苷酶，使淀粉分解为葡萄糖的速度减缓，减少和延缓小肠对葡萄糖的吸收，以降低血糖，对餐后高血糖的作用比较明显。葡萄糖苷酶抑制剂不刺激胰岛素的分泌，单独使用本类药物通常不会引发低血糖，因此可帮助减少血糖的波动。可以明显降低糖尿病患者发生心血管病变的概率，对心肌梗死的改善作用最为显著。常用的α-葡萄糖苷酶抑制剂主要是阿卡波糖、伏格列波糖。但是仍然出现少数腹胀、腹痛、腹泻、恶心、呕吐，也可出现胃肠痉挛性疼痛、顽固性便秘等不良反应。
我国传统中草药在人们防病治病中起着毋庸置疑的作用，从传统中草药中挖掘活性成分是自主知识产权新药研发的重要手段和科技前沿，符合国际药物研发趋势，具有广阔的应用前景。石斛为“中华九大仙草”之首，其味淡微咸，具有健脾生津，滋阴养胃、润肺止咳等功能。是重要的药食两用药材，对人体和环境安全友好。
现有的研究资料表明一些中药的一些酚性成分具有显著的α-葡萄糖苷酶抑制活性，提示医疗可用做降糖药物。应该考虑传统中药中筛选发现α-葡萄糖苷酶抑制活性酚性成分，并通过化学方法进行合成。因此，开发具有低毒性且疗效显著的α-葡萄糖苷酶抑制活性医用药物，对人类社会具 有显著的社会和经济效益前景。
发明内容
有鉴于此，本发明提供了短棒石斛、聚石斛和红牙刷石斛的提取物及其主要成分化合物作为α-葡萄糖苷酶抑制剂的应用，使得所述提取物和化合物对具有α-葡萄糖苷酶抑制活性，具有降血糖显著疗效，且安全性高，无毒副作用。
为了实现上述发明目的，本发明提供以下技术方案：
本发明提供了石斛提取物，其主要成分化合物包括Chrysotobibenzyl、Gigantol、Chrysotoxine、5-Hydroxy-3,4,3',4',5'-pentamethoxybibenzyl、Brittonin A、4,5,4'-trihydroxy-3,3'-dimethoxybibenzyl或Cypripedin中的一个或多个。
在本发明的一些具体实施方案中，所述石斛提取物的制备方法包括：取石斛晾干粉碎，2倍乙醇提取3次，浓缩，经1倍石油醚萃取脱脂3次后，调整pH值9.0～10.0、过滤，1倍乙酸乙酯萃取3次，浓缩，获得乙酸乙酯部分，获得石斛提取物。
在本发明的一些具体实施方案中，所述石斛包括短棒石斛、聚石斛或红牙刷石斛中的一种或多种。具体的，所述石斛来源于植物短棒石斛(学名：Dendrobium capillipes Rchb.f.)、聚石斛(学名：Dendrobium lindleyi Stendel)和红牙刷石斛(学名：Dendrobium secundum(Blume)Lindl.)提取分离或通过化学合成。
本发明还提供了所述的石斛提取物或其主要成分化合物在制备α-葡萄糖苷酶抑制剂中的应用。
在本发明的一些具体实施方案中，所述其主要成分化合物包括Chrysotobibenzyl、Gigantol、Chrysotoxine、5-Hydroxy-3,4,3',4',5'-pentamethoxybibenzyl、Brittonin A、4,5,4'-trihydroxy-3,3'-dimethoxybibenzyl或Cypripedin中的一个或多个。
本发明还提供了所述的石斛提取物或其主要成分化合物在制备预防和/或治疗糖尿病的药物中的应用。
在本发明的一些具体实施方案中，所述其主要成分化合物包括Chrysotobibenzyl、Gigantol、Chrysotoxine、5-Hydroxy-3,4,3',4',5'-pentamethoxybibenzyl、Brittonin A、4,5,4'-trihydroxy-3,3'-dimethoxybibenzyl或Cypripedin中的一个或多个。
本发明还提供了α-葡萄糖苷酶抑制剂，包括所述的石斛提取物或其主要成分化合物；所述其主要成分化合物包括Chrysotobibenzyl、Gigantol、Chrysotoxine、5-Hydroxy-3,4,3',4',5'-pentamethoxybibenzyl、Brittonin A、4,5,4'-trihydroxy-3,3'-dimethoxybibenzyl或Cypripedin中的一个或多个。
本发明还提供了预防和/或治疗糖尿病的药物，包括所述的石斛提取物或其主要成分化合物；所述其主要成分化合物包括Chrysotobibenzyl、Gigantol、Chrysotoxine、5-Hydroxy-3,4,3',4',5'-pentamethoxybibenzyl、Brittonin A、4,5,4'-trihydroxy-3,3'-dimethoxybibenzyl或Cypripedin中的一个或多个，以及药学上可接受的辅料。
在本发明的一些具体实施方案中，所述药物的剂型包括水溶剂或固体剂；所述固体及包括片剂、颗粒剂、胶囊剂、散剂、丸剂中的一种或多种。
本发明公开了短棒石斛、聚石斛和红牙刷石斛的提取物及其主要成分化合物作为α-葡萄糖苷酶抑制剂的应用。本发明利用植物提取分离方法获得的提取物及其主要成分，其能够有效地抑制α-葡萄糖苷酶活性，并且对人体无毒副作用和药物依赖型，抑制α-葡萄糖苷酶活性实验药效优于现有的常用西药，可以广泛应用于降低餐后高血糖，降低心血管并发症的发生率，干预胰岛素依赖型或非胰岛素依赖型的口服降糖药制备。
附图说明
为了更清楚地说明本发明实施例或现有技术中的技术方案，下面将对实施例或现有技术描述中所需要使用的附图作简单地介绍。
图1示三种石斛提取物和9种化合物的植物化学制备流程。
具体实施方式
本发明公开了短棒石斛、聚石斛和红牙刷石斛的提取物及其主要成分 化合物作为α-葡萄糖苷酶抑制剂的应用，本领域技术人员可以借鉴本文内容，适当改进工艺参数实现。特别需要指出的是，所有类似的替换和改动对本领域技术人员来说是显而易见的，它们都被视为包括在本发明。本发明的方法及应用已经通过较佳实施例进行了描述，相关人员明显能在不脱离本发明内容、精神和范围内对本文所述的方法和应用进行改动或适当变更与组合，来实现和应用本发明技术。
本发明的目的在于提供三种石斛提取物及其主要成分化合物的应用，使得所述提取物和化合物对具有α-葡萄糖苷酶抑制活性，具有降血糖显著疗效，且安全性高，无毒副作用。
为了实现上述目的，本发明提供如下技术方案：
化合物的结构如式I所式：
Figure PCTCN2021093731-appb-000001
式I 七种化合物的结构
上述药物化学名称为：
Chrysotobibenzyl，无色油状，ESI-MS m/z:[M+Na] +355，分子式C 19H 24O 5， 13C NMR(CD 3OD,125MHz):δ C:139.3s,110.2d,148.3s,144.5s,113.5d,116.8d,137.0s,106.8d,144.5s,134.6s,144.5s,106.8d,39.0t,38.7t,56.3q,56.3q,56.3q,56.3q,56.5q。一种短棒石斛、聚石斛或红牙刷石斛茎 中提取分离的联苄类物质，为已知化合物，未见α-葡萄糖苷酶抑制活性报道。
Gigantol，无色油状，ESI-MS m/z:[M+Na] +297，分子式C 16H 18O 4, 13C-NMR(CDCl 3125MHz)δ C:160.8s,156.6s,146.3s,144.5s,143.7s,133.7s,121.0d,114.2d,111.2d,108.1d,106.8d,99.ld,55.9q,55.3q,38.2t,37.2t.。一种短棒石斛、聚石斛或红牙刷石斛茎中提取分离的联苄类物质，为已知化合物，未见α-葡萄糖苷酶抑制活性报道。
Chrysotoxine，无色油状，ESI-MS m/z:[M+Na] +341，分子式C 18H 22O 5, 13C-NMR(CDCl 3125MHz)δ C:148.6s,147.1s,146.4s,146.5s,134.2s,132.8s,132.3s,120.2d,111.7d,111.0d,105.0d,105.1d,56.1q,55.8q,55.9q,55.4q,37.8t,37.5t。一种短棒石斛、聚石斛或红牙刷石斛茎中提取分离的联苄类物质，为已知化合物，未见α-葡萄糖苷酶抑制活性报道。
5-Hydroxy-3,4,3',4',5'-pentamethoxybibenzyl，无色油状，ESI-MS m/z:[M+Na] +371，分子式C 19H 24O 6， 13C-NMR(CDCl 3125MHz)δ C:137.9s,108.0d,149.0s,133.5s,152.1s,104.3d,137.2s,105.6d,153.1s,136.3s,153.0s,105.4d,55.6q,56.1q,60.8q,60.9q,38.0t,38.1t。一种短棒石斛、聚石斛或红牙刷石斛茎中提取分离的联苄类物质，为已知化合物，未见α-葡萄糖苷酶抑制活性报道。
Brittonin A，无色油状，ESI-MS m/z:[M+Na] +385，分子式C 20H 26O 6， 13C-NMR(CDCl 3125MHz)δ C:136.5s×2,152.7s×4,137.4s×2,105.3d×4,56.2q×4,61.0q×2,38.3t×2。一种短棒石斛、聚石斛或红牙刷石斛茎中提取分离的联苄类物质，为已知化合物，未见α-葡萄糖苷酶抑制活性报道。
4,5,4'-trihydroxy-3,3'-dimethoxybibenzyl，无色油状，ESI-MS m/z:[M+Na] +313，分子式C 16H 18O 5， 13C-NMR(CDCl 3125MHz)δ C:130.5s,103.4d,146.7s,133.2s,143.8s,108.5d,133.9d,111.3d,146.5s,143.8s,114.3d,121.3d,55.6q,56.1q,55.8q,38.3t,37.8t。一种短棒石斛、聚石斛或红牙刷石斛茎中提取分离的联苄类物质，为已知化合物，未见α-葡萄糖苷酶抑制活性报道。
Cypripedin，无色晶体，ESI-MS m/z:[M+Na] +307，分子式C 16H 12O 5， 13C NMR(CD 3OD,125MHz)δ C:190.0s,181.5s,159.3s,149.9s,140.1s, 134.5s,130.2s,128.4s,127.1d,126.6d,125.4s,123.3d,122.5d,112.0d,61.4q,56.9q。。一种短棒石斛、聚石斛或红牙刷石斛茎中提取分离的菲类物质，为已知化合物，未见α-葡萄糖苷酶抑制活性报道。
制备方法：短棒石斛(学名：Dendrobium capillipes Rchb.f.)、聚石斛(学名：Dendrobium lindleyi Stendel)和红牙刷石斛(学名：Dendrobium secundum(Blume)Lindl.)的植物晾干粉碎后，2倍乙醇提取3次，浓缩至浑浊(体积1/10)，经1倍石油醚萃取脱脂3次后，经过调整pH值(9.0-10.0)过滤后，1倍乙酸乙酯萃取3次浓缩获得乙酸乙酯部分，作为发明的目的提取物。乙酸乙酯部分经硅胶柱(200-300目，石油醚：乙酸乙酯10:1、5:1、3:1、2:1、1:1和1:2)层析分别分为A-F段，经标准品确定化合物所在部位，重点分离。化合物所在部位经ODS、MCI和正相硅胶等反复色谱分离后纯化或析出结晶，过滤结晶获得单体化合物。
例如：10Kg短棒石斛(学名：D.capillipes Rchb.f.)，乙酸乙酯部分A段经ODS层析柱(甲醇水溶液30％-100％)获得Chrysotobibenzyl(136mg)(50％甲醇)和Brittonin A(69mg)(60％甲醇)，B段获得Cypripedin(67mg)，C段获得5-Hydroxy-3,4,3',4',5'-pentamethoxybibenzyl(77mg)，D段获得Chrysotoxine(235mg)，E段获得Gigantol(381mg)；10Kg聚石斛(学名：D.lindleyi Stendel)乙酸乙酯部分A段经ODS层析柱(甲醇水溶液30％-100％)获得Chrysotobibenzyl(78mg)(50％甲醇)和Brittonin A(33mg)(60％甲醇)，B段获得Cypripedin(25mg)，C段获得5-Hydroxy-3,4,3',4',5'-pentamethoxybibenzyl(167mg)，E段获得Gigantol(481mg)，F段获得4,5,4'-trihydroxy-3,3'-dimethoxybibenzyl(83mg)；10kg红牙刷石斛(学名：D.secundum(Blume)Lindl.)乙酸乙酯部分A段经ODS层析柱(甲醇水溶液30％-100％)获得Chrysotobibenzyl(89mg)(50％甲醇)和Brittonin A(96mg)(60％甲醇)，B段获得Cypripedin(157mg)，C段获得5-Hydroxy-3,4,3',4',5'-pentamethoxybibenzyl(168mg)，D段获得Chrysotoxine(55mg)，E段获得Gigantol(421mg)，F段获得4,5,4'-trihydroxy-3,3'-dimethoxybibenzyl(44mg)(流程见图1)。
在制备α-葡萄糖苷酶抑制剂药物的应用中，本发明所述化合物可按本 领域常规制剂方法制备成各种农用或临床上常规制剂，例如，可以向本发明有效量的剂量下加入药学上可接受辅料(例如崩解剂、润滑剂、黏合剂、分散剂等)，制备成各种口服药剂，本发明优选制成片剂、颗粒剂、胶囊剂、散剂、丸剂或口服液。
对于本领域技术人员来说，在知晓活性成分的情况下，可根据常规的制剂方法，轻易的制成各种药剂产品，同时在制备中所采用的辅料也为本领域所公知，如羧甲淀粉钠、蔗糖粉、蜂蜜、芝麻油等。
在本发明所述化合物与现有药物阿卡波糖对比试验中，本发明所述提取物和主要化合物药物活性优于阿卡波糖，毒性和残留低于阿卡波糖。
同时，在对本发明所述化合物的动物急性毒性和长期毒性的研究中未发现本发明所述化合物有任何不良反应，对各器官无损伤。在临床试验中，本发明所述化合物对糖尿病患者降低餐后血糖有明显的疗效，且无毒副作用和药物依赖性。
由以上技术方案可知，本发明安全可靠，医用可以糖尿病患者降低餐后血糖，并且对人体无毒副作用和药物依赖型，优于现有的医药，可以广泛应用于降低餐后高血糖，降低心血管并发症的发生率，干预胰岛素依赖型或非胰岛素依赖型的口服降糖药制备。
本发明提供的短棒石斛、聚石斛和红牙刷石斛的提取物及其主要成分化合物作为α-葡萄糖苷酶抑制剂的应用中，所用原料及试剂均可由市场购得。
下面结合实施例，进一步阐述本发明：
实施例1 提取物的制备
短棒石斛(学名：Dendrobium capillipes Rchb.f.)、聚石斛(学名：Dendrobium lindleyi Stendel)和红牙刷石斛(学名：Dendrobium secundum(Blume)Lindl.)的植物晾干粉碎后，2倍乙醇提取3次，浓缩至浑浊(体积1/10)，经1倍石油醚萃取脱脂3次后，经过调整pH值(9.0-10.0)过滤后，1倍乙酸乙酯萃取3次浓缩获得乙酸乙酯部分，作为发明的目的提取物。
乙酸乙酯部分经硅胶柱(200-300目，石油醚：乙酸乙酯10:1、5:1、3:1、2:1、1:1和1:2)层析分别分为A-F段，经标准品确定化合物所在部位，重点分离。化合物所在部位经ODS、MCI和正相硅胶等反复色谱分离后纯化或析出结晶，过滤结晶获得单体化合物。
10Kg短棒石斛(学名：D.capillipes Rchb.f.)，乙酸乙酯部分A段经ODS层析柱(甲醇水溶液30％-100％)获得Chrysotobibenzyl(136mg)(50％甲醇)和Brittonin A(69mg)(60％甲醇)，B段获得Cypripedin(67mg)，C段获得5-Hydroxy-3,4,3',4',5'-pentamethoxybibenzyl(77mg)，D段获得Chrysotoxine(235mg)，E段获得Gigantol(381mg)；10Kg聚石斛(学名：D.lindleyi Stendel)乙酸乙酯部分A段经ODS层析柱(甲醇水溶液30％-100％)获得Chrysotobibenzyl(78mg)(50％甲醇)和Brittonin A(33mg)(60％甲醇)，B段获得Cypripedin(25mg)，C段获得5-Hydroxy-3,4,3',4',5'-pentamethoxybibenzyl(167mg)，E段获得Gigantol(481mg)，F段获得4,5,4'-trihydroxy-3,3'-dimethoxybibenzyl(83mg)；10kg红牙刷石斛(学名：D.secundum(Blume)Lindl.)乙酸乙酯部分A段经ODS层析柱(甲醇水溶液30％-100％)获得Chrysotobibenzyl(89mg)(50％甲醇)和Brittonin A(96mg)(60％甲醇)，B段获得Cypripedin(157mg)，C段获得5-Hydroxy-3,4,3',4',5'-pentamethoxybibenzyl(168mg)，D段获得Chrysotoxine(55mg)，E段获得Gigantol(421mg)，F段获得4,5,4'-trihydroxy-3,3'-dimethoxybibenzyl(44mg)(流程见图1)。
实施例2 制备本发明所述化合物的胶囊剂
按下述重量称取各原料(单位：g)：
对三种石斛按照实施例1的提取方法制备的目的提取物或分离的七种主要成分化合物Chrysotobibenzyl、Gigantol、Chrysotoxine、5-Hydroxy-3,4,3',4',5'-pentamethoxybibenzyl、Brittonin A、4,5,4'-trihydroxy-3,3'-dimethoxybibenzyl和Cypripedin各50g。
将对提取物或化合物分别加入乙醇100mL，过滤，加入羧甲淀粉钠，充分混匀，喷雾干燥制成颗粒，分别装入1号胶囊，即得胶囊剂。
实施例3 制备本发明所述化合物的片剂
按下述重量称取各原料(单位：g)：
对三种石斛按照实施例1的提取方法制备的目的提取物或分离的七种主要成分化合物Chrysotobibenzyl、Gigantol、Chrysotoxine、5-Hydroxy-3,4,3',4',5'-pentamethoxybibenzyl、Brittonin A、4,5,4'-trihydroxy-3,3'-dimethoxybibenzyl和Cypripedin各50g。
将对提取物或化合物分别加入乙醇100mL，过滤，加入羧甲淀粉钠，充分混匀，喷雾干燥制成颗粒，分别送至压片机压片即得。
实施例4 制备本发明所述化合物的丸剂
按下述重量称取各原料(单位：g)：
对三种石斛按照实施例1的提取方法制备的目的提取物或分离的七种主要成分化合物Chrysotobibenzyl、Gigantol、Chrysotoxine、5-Hydroxy-3,4,3',4',5'-pentamethoxybibenzyl、Brittonin A、4,5,4'-trihydroxy-3,3'-dimethoxybibenzyl和Cypripedin各50g。
将对提取物或化合物分别加入乙醇100mL，过滤，加入羧甲淀粉钠，充分混匀，喷雾干燥制成颗粒，接着加入纯芝麻油或者蜂蜜混匀，分别送至离心造丸机制成丸剂。
实施例5 本发明提供的提取物或化合物的体外α-葡萄糖苷酶抑制活性
所有待测样品以及阳性对照均用DMSO溶解；本发明实施例1提供的提取物或单体化合物先粗筛，一般终浓度最大值200μM，可适当调整；若测IC 50值，再稀释几个浓度，按相同的方法检测即可。若为粗样，一般终浓度最大值200μg/mL，可适当调整。
待测样品溶液的配制：取450μL配置好的0.2U/ml的α-葡萄糖苷酶溶液于EP管中，再加入45μL的待测溶液，摇匀，取110μL于96孔板中(4次重复)；(阴性与空白：取450μL配置好的0.2U/ml的α-葡萄糖苷酶溶液于EP管中，再加入45μL的DMSO，摇匀，取110μL溶液于96孔板中(4次重复))；将96孔板于37℃放置15分钟后，待测组加入40μL PNPG 溶液；(空白：加入40μL PBS溶液(0.1mol/L))；将96孔板于37℃放置15分钟后，于405nm波长下检测每孔的OD值。
计算化合物对α-糖苷酶的抑制活性，计算公式如下：
抑制率＝(OD DMSO-OD 样)/(OD DMSO-OD PBS)×100％
若样品的颜色较深，需除去本底吸收：只需多做2-3组平行，将加入的40μL底物(PNPG溶液)换成40μL PBS溶液即可。计算化合物对α-糖苷酶的抑制活性，计算公式如下：
抑制率＝(OD DMSO-(OD 样-OD 本底))/(OD DMSO-OD PBS)×100％(实验组/阳性对照)：10μL待测样品溶液+100μL PBS溶液溶解的0.2U/mLα-糖苷酶溶液+40μL的2.5mmol/L PNPG溶液(OD 样)。
阴性：10μLDMSO溶液+100μL PBS溶液溶解的0.2U/mLα-糖苷酶溶液+40μL的2.5mmol/L PNPG溶液(OD DMSO)。
空白：10μLDMSO溶液+100μL PBS溶液溶解的0.2U/mLα-糖苷酶溶液+40μL的0.1mol/L的PBS溶液(OD PBS)。
本底：10μL待测样品溶液+100μL PBS溶液溶解的0.2U/mLα-糖苷酶溶液+40μL的0.1mol/L的PBS溶液(OD 本底)。
表1.化合物体外α-葡萄糖苷酶抑制活性
Figure PCTCN2021093731-appb-000002
Figure PCTCN2021093731-appb-000003
通过表1的结果显示，三种石斛的提取物在(200μg/mL)表现出很强的α-葡萄糖苷酶抑制活性，抑制率均超过92％；其主要成分化合物也表现得比现有的阳性对照药物阿卡波糖还要好，IC 50值分别达到77.17-131.21μM，其毒性也比阳性对照药物阿卡波糖强，CC 50大于200mM，从而使化合物具有更好的安全性。这说明三种石斛的提取物及其主要成分化合物具有很好的体外α-葡萄糖苷酶抑制活性和很好的安全性。
实施例6 本发明所述化合物毒性研究
1、急性毒性研究
取昆明种小鼠，按1g/kg灌胃给予本发明药物(实施例3所制备的提取物和化合物胶囊内粉末)，1天连续给药4次，每次间隔6h，然后给予正常饮食，对各个器官进行病理性检查，未发现脏器病变。
2、长期毒性研究
取昆明种小鼠，按中、大剂量组(1g/kg，2g/kg)灌胃给予本发明药物(实施例3所制备的化合物胶囊内粉末)，每天1次，连续给药14天后，测定小鼠体重、心功能、肝功能、肾功能、心电图等指标，给药组分别与对照组比较，未见明显异常。病理学检查心、肝、肾、脾、肺、胃、十二指肠、大肠、小肠、肾上腺和生殖器等脏器，给药组分别与对照组比较，均未见明显中毒性改变。以上结果表明本发明所述提取物和化合物安全无毒，可用于临床。
实施例7 本发明所述提取物和化合物制剂的分别进行了临床试验
1、试验对象资料
单一组：女27例，男19例，病程2～9(5.72±1.49)年，年龄63～78(70.24±3.51)岁。以甘精胰岛素皮下注射，10U/次，1次/d。
联合用药组：老年T2DM患者，随机平分联合组女25例，男21例，病程3～8(5.34±1.08)年，年龄62～76(68.89±3.37)岁以甘精胰岛素+口服提取物和化合物制剂(实施例1胶囊)50mg/次，3次/d。持续治疗3个月。
联合用药组(含三种石斛提取物，七种化合物和阳性对照阿卡波糖)共12组，每组46病例。
2、临床结果
2.1、临床主要症状体征改善情况，未住院。
治疗后联合组餐后检查2h血糖(2hPG)、空腹血糖(FPG)、糖化血红蛋白(HbA1c)。数据采用SPSS 22.0统计学软件，计量资料以
Figure PCTCN2021093731-appb-000004
表示、t检验，计数资料用n(％)表示、χ 2检验。
2.2、各种检查结果
联合组总有效率93.5％与单一组84.6％(P＞0.05)。治疗后2组2hPG、FPG、HbA1c降低，且联合组低于单一组，联合组低血糖发生率2.18％低于单一组19.6％、胃肠道反应发生率10.87％低于单一组28.26％(P＜0.05)。(结果见表2)
表2.提取物和化合物制剂降血糖临床试验
Figure PCTCN2021093731-appb-000005
Figure PCTCN2021093731-appb-000006
2.3、临床结果总结。
①、三种提取物和七种化合物胶囊分别对46例糖尿病患者(T2DM患者)临床治疗综合观察，结果表明，此药作为口服降血糖药物对糖尿病患者联合胰岛素使用，具有明确的降血糖疗效。
②、毒副作用观察结果：所治疗的每组例患者，没有一例患者出现任何不良反应，说明本发明药物对人体是安全的。
上述临床观察结果表明本发明化合物用于治疗糖尿病患者，辅助降低餐后血糖疗效显著，无毒副作用，无药物依赖性。
以上对本发明所提供的短棒石斛、聚石斛和红牙刷石斛的提取物作为α-葡萄糖苷酶抑制剂的应用进行了详细介绍。本文应用了具体个例对本发明的原理及实施方式进行了阐述，以上实施例的说明只是用于帮助理解本发明的方法及其核心思想。应当指出，对于本技术领域技术人员来说，在不脱离本发明原理的前提下，还可以对本发明进行若干改进和修饰，这 些改进和修饰也落入本发明权利要求的保护范围内。

Claims (10)

  1. 石斛提取物，其特征在于，其主要成分化合物包括Chrysotobibenzyl、Gigantol、Chrysotoxine、5-Hydroxy-3,4,3',4',5'-pentamethoxybibenzyl、Brittonin A、4,5,4'-trihydroxy-3,3'-dimethoxybibenzyl或Cypripedin中的一个或多个。
  2. 如权利要求1所述的石斛提取物，其特征在于，其制备方法包括：取石斛晾干粉碎，2倍乙醇提取3次，浓缩，经1倍石油醚萃取脱脂3次后，调整pH值9.0～10.0、过滤，1倍乙酸乙酯萃取3次，浓缩，获得乙酸乙酯部分，获得石斛提取物。
  3. 如权利要求1或2所述的石斛提取物，其特征在于，所述石斛包括短棒石斛、聚石斛或红牙刷石斛中的一种或多种。
  4. 如权利要求1至3任一项所述的石斛提取物或其主要成分化合物在制备α-葡萄糖苷酶抑制剂中的应用。
  5. 如权利要求4所述的应用，其特征在于，所述其主要成分化合物包括Chrysotobibenzyl、Gigantol、Chrysotoxine、5-Hydroxy-3,4,3',4',5'-pentamethoxybibenzyl、Brittonin A、4,5,4'-trihydroxy-3,3'-dimethoxybibenzyl或Cypripedin中的一个或多个。
  6. 如权利要求1至3任一项所述的石斛提取物或其主要成分化合物在制备预防和/或治疗糖尿病的药物中的应用。
  7. 如权利要求6所述的应用，其特征在于，所述其主要成分化合物包括Chrysotobibenzyl、Gigantol、Chrysotoxine、5-Hydroxy-3,4,3',4',5'-pentamethoxybibenzyl、Brittonin A、4,5,4'-trihydroxy-3,3'-dimethoxybibenzyl或Cypripedin中的一个或多个。
  8. α-葡萄糖苷酶抑制剂，其特征在于，包括如权利要求1至3任一项所述的石斛提取物或其主要成分化合物；所述其主要成分化合物包括Chrysotobibenzyl、Gigantol、Chrysotoxine、5-Hydroxy-3,4,3',4',5'-pentamethoxybibenzyl、Brittonin A、4,5,4'-trihydroxy-3,3'-dimethoxybibenzyl或Cypripedin中的一个或多个。
  9. 预防和/或治疗糖尿病的药物，包括如权利要求1至3任一项所述的石斛提取物或其主要成分化合物；所述其主要成分化合物包括Chrysotobibenzyl、Gigantol、Chrysotoxine、5-Hydroxy-3,4,3',4',5'-pentamethoxybibenzyl、Brittonin A、4,5,4'-trihydroxy-3,3'-dimethoxybibenzyl或Cypripedin中的一个或多个，以及药学上可接受的辅料。
  10. 如权利要求9所述的药物，其特征在于，所述药物的剂型包括水溶剂或固体剂；所述固体及包括片剂、颗粒剂、胶囊剂、散剂、丸剂中的一种或多种。
PCT/CN2021/093731 2021-05-14 2021-05-14 短棒石斛、聚石斛和红牙刷石斛的提取物作为α-葡萄糖苷酶抑制剂的应用 WO2022236790A1 (zh)

Priority Applications (1)

Application Number Priority Date Filing Date Title
PCT/CN2021/093731 WO2022236790A1 (zh) 2021-05-14 2021-05-14 短棒石斛、聚石斛和红牙刷石斛的提取物作为α-葡萄糖苷酶抑制剂的应用

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
PCT/CN2021/093731 WO2022236790A1 (zh) 2021-05-14 2021-05-14 短棒石斛、聚石斛和红牙刷石斛的提取物作为α-葡萄糖苷酶抑制剂的应用

Publications (1)

Publication Number Publication Date
WO2022236790A1 true WO2022236790A1 (zh) 2022-11-17

Family

ID=84028754

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/CN2021/093731 WO2022236790A1 (zh) 2021-05-14 2021-05-14 短棒石斛、聚石斛和红牙刷石斛的提取物作为α-葡萄糖苷酶抑制剂的应用

Country Status (1)

Country Link
WO (1) WO2022236790A1 (zh)

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN108083993A (zh) * 2018-01-08 2018-05-29 遵义医学院 一种龟背石斛成分及其制备分离方法

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN108083993A (zh) * 2018-01-08 2018-05-29 遵义医学院 一种龟背石斛成分及其制备分离方法

Non-Patent Citations (4)

* Cited by examiner, † Cited by third party
Title
TAN CAI-YIN;MEI WEN-LI;ZHAO YOU-XING;HUANG SHENG-ZHUO;KONG FAN-DONG;YANG NING-NING;SONG XI-QIANG;DAI HAO-FU: "Chemical Constituents from Dendrobium sinense", JOURNAL OF TROPICAL AND SUBTROPICAL BOTANY, vol. 25, no. 2, 30 April 2017 (2017-04-30), pages 189 - 194, XP093004938, DOI: 10.11926/jtsb.3668 *
TAN ZHEZHEN , XU LIJIA , CHEN SIBAO: "Research Progress of α-Glucosidase Inhibitors Derived from Plant Sources", CENTRAL SOUTH PHARMACY, vol. 16, no. 7, 15 June 2018 (2018-06-15), pages 982 - 987, XP093004955, ISSN: 1672-2981, DOI: 10.7539/j.issn.1672-2981.2018.07.020 *
YAN MEI-QIU;YANG ZHI-YUAN;SHI QIU-QIU;WANG TING;CHEN SU-HONG;LV GUI-YUAN: "Research Progress on Protective Effects and Mechanism of Dendrobii Caulis on Metabolic Disturbances", CHINESE HERBAL MEDICINES, vol. 50, no. 10, 28 May 2019 (2019-05-28), pages 2491 - 2497, XP093004944, ISSN: 0253-2670, DOI: 10.7501/j.issn.0253-2670.2019.10.033 *
ZHANG XUE-QIN , ZHAO TING-MEI , LIU JING , ZHAO RUO-XI , ZHENG SHI-GANG , CHUN ZE , HU YA-DONG: "Advances in Chemical Compounds and Pharmacological Effects of Dendrobii Caulis", CHINESE HERBAL MEDICINES, vol. 49, no. 13, 12 July 2018 (2018-07-12), pages 3174 - 3182, XP093004952, ISSN: 0253-2670, DOI: 10.7501/j.issn.0253-2670.2018.13.033 *

Similar Documents

Publication Publication Date Title
Prince et al. Antidiabetic and antihyperlipidaemic effect of alcoholic Syzigium cumini seeds in alloxan induced diabetic albino rats
EP1800685B1 (en) Steroidal saponin pharmaceutical composition, its preparation method and use
Anaya-Eugenio et al. Hypoglycemic properties of some preparations and compounds from Artemisia ludoviciana Nutt
WO2010140734A1 (ko) 2,5-비스-아릴-3,4-디메틸테트라하이드로퓨란 리그난을 유효성분으로 포함하는 에이엠피케이의 활성화에 의해 매개되는 비만 관련 질환의 예방 또는 치료용 조성물
CN101747405A (zh) 小檗碱甘草酸对映体盐及其制备方法和用途
US6376682B1 (en) Compound with α-glucosidase inhibiting action and method for producing the same
CN105287511B (zh) 土甘草a的应用
CN104513290B (zh) 雷醇内酯衍生物及其应用
CN108605931A (zh) 四种化合物在制备杀线虫药物中的应用
WO2022236790A1 (zh) 短棒石斛、聚石斛和红牙刷石斛的提取物作为α-葡萄糖苷酶抑制剂的应用
CN101849950A (zh) 救必应酸在制备调血脂的药物中的应用
CN108314620B (zh) 异序乌桕素i和j及其药物组合物和其应用
CN104945455B (zh) 香豆素苷类化合物、其制法和药物组合物与用途
KR100979459B1 (ko) 근육세포에서 포도당 흡수를 증가시키는 데이츄 추출물과이로부터 분리한 4ｈ-크로멘-4-온 유도체
Bekele et al. Antidiabetic activity and phytochemical screening of crude extracts of Stevia rebaudiana Bertoni and Ajuga remota Benth grown in Ethiopia on alloxan-induced diabetic mice
CN108403980B (zh) 一种降血糖植物提取物有效部位及其制备方法和应用
WO2022236789A1 (zh) 华石斛、密花石斛或本斯石斛的提取物及其主要成分作为抗炎症制剂的应用
JP7157253B2 (ja) 潤腸便通の漢方薬組成物、その調製方法及びその用途
CN113262271A (zh) 短棒石斛、聚石斛和红牙刷石斛的提取物作为α-葡萄糖苷酶抑制剂的应用
CN107778340A (zh) (20S,24R)‑20,24‑环氧达玛烷‑3β,12β,25‑三醇及其应用
CN103613632B (zh) 29-降齐墩果烷酸类化合物及其制备方法和在制备糖苷酶抑制剂药物中的应用
CN113633718A (zh) 华石斛、密花石斛或本斯石斛的提取物及其主要成分作为抗炎症制剂的应用
KR100767051B1 (ko) 오보바톨 또는 오보바탈의 분리방법과 이를 유효성분으로함유하는 비만치료 및 예방용 조성물 및 상기 유효성분의정제방법
WO1998025639A1 (en) HYPOGLYCEMIC AGENTS FROM HARUNGANA OR $i(VISMIA SPP.)
CN109646444A (zh) 白藜芦醇苷在降低血糖的药物或保健品中的应用及效果评价方法

Legal Events

Date Code Title Description
121 Ep: the epo has been informed by wipo that ep was designated in this application

Ref document number: 21941361

Country of ref document: EP

Kind code of ref document: A1

NENP Non-entry into the national phase

Ref country code: DE

122 Ep: pct application non-entry in european phase

Ref document number: 21941361

Country of ref document: EP

Kind code of ref document: A1