WO2024078507A1 - Utilisation d'ergostérol dans la préparation d'un médicament pour la prévention et le traitement d'ulcères gastriques - Google Patents

Utilisation d'ergostérol dans la préparation d'un médicament pour la prévention et le traitement d'ulcères gastriques Download PDF

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Publication number
WO2024078507A1
WO2024078507A1 PCT/CN2023/123828 CN2023123828W WO2024078507A1 WO 2024078507 A1 WO2024078507 A1 WO 2024078507A1 CN 2023123828 W CN2023123828 W CN 2023123828W WO 2024078507 A1 WO2024078507 A1 WO 2024078507A1
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WIPO (PCT)
Prior art keywords
ergosterol
gastric
drug
preventing
gastric ulcers
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PCT/CN2023/123828
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English (en)
Chinese (zh)
Inventor
许艺飞
郭绍举
黄萍
洪欣欣
李海文
李娟娟
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深圳市中医院
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Application filed by 深圳市中医院 filed Critical 深圳市中医院
Publication of WO2024078507A1 publication Critical patent/WO2024078507A1/fr

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    • 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
    • A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
    • A61K31/575—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids substituted in position 17 beta by a chain of three or more carbon atoms, e.g. cholane, cholestane, ergosterol, sitosterol
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants

Definitions

  • the invention belongs to the technical field of biomedicine, and particularly relates to the application of ergosterol in the preparation of medicines for preventing and treating gastric ulcers.
  • Gastric ulcer is a common clinical disease. There are many factors that cause gastric ulcer, including drugs and diet (excessive drinking, use of nonsteroidal anti-inflammatory drugs, etc.), mental factors (high life pressure, high mental tension, etc.), genetic factors, etc. If gastric ulcer is not treated in time, it may also induce upper gastrointestinal bleeding, gastric perforation, pyloric obstruction and even gastric cancer. Clinically, proton pump inhibitors are often used to treat gastric ulcers. The treatment time is usually 1 to 2 months. Long-term use of proton pump inhibitors will inhibit the secretion of pepsin and also have a certain negative impact on the acid-secreting glands. Accelerating the recovery of gastric ulcers and reducing the use of proton pump inhibitors are one of the important clinical problems to be solved.
  • Ergosterol also known as ergosterol, is a white or colorless shiny small leaf crystal or white crystalline powder. As an important component of fungal cell membrane, ergosterol has a stable structure and strong specificity. It is more representative than glucosamine for measuring biomass. Due to its unique physiological effects, ergosterol is widely used in drug development, but there is no record of ergosterol in the treatment of gastric ulcers.
  • the purpose of the present invention is to enrich the medical uses of ergosterol and effectively prevent and treat gastric ulcer.
  • the present invention provides the use of ergosterol in preparing a drug for preventing and treating gastric ulcer.
  • the ergosterol is the only active ingredient.
  • the triggering factors of gastric ulcer include alcohol and/or acid.
  • the alcohol is anhydrous ethanol.
  • the acid is acetic acid.
  • the target of the drug is Ror ⁇ protein.
  • the prevention and treatment of gastric ulcer includes promoting gastric mucus secretion and/or activating gastric stem cells.
  • the dosage form of the drug includes any one of powder, injection, capsule, tablet, pill, granule and oral solution.
  • the present invention also provides a medicine for preventing and treating gastric ulcer, which comprises ergosterol and medically acceptable auxiliary materials.
  • the ergosterol is used as the only active ingredient of the drug.
  • the present invention also provides a method for preventing and treating gastric ulcer, comprising administering ergosterol by intragastric administration at a dosage of 50-500 mg ergosterol/d/person.
  • the present invention provides the use of ergosterol in the preparation of a drug for preventing and treating gastric ulcers.
  • the ergosterol of the present invention can promote the secretion of gastric mucus, resist gastric ulcers caused by anhydrous ethanol, and promote the recovery of gastric ulcers caused by acetic acid, and can be used for preventing and treating gastric ulcers.
  • FIG1 shows the preventive effect of ergosterol on acute gastric ulcer in rats induced by anhydrous ethanol
  • FIG2 shows the therapeutic effect of ergosterol on gastric ulcer in mice induced by acetic acid
  • FIG3 is the molecular docking result of ergosterol and RoR ⁇ on gastric stem cells
  • FIG4 shows the change of the root mean square deviation (RMSD) of the complex over time during the molecular dynamics simulation.
  • the invention provides application of ergosterol in preparing medicine for preventing and treating gastric ulcer.
  • the ergosterol described in the present invention is a type of component with cyclopentane polyhydrophenanthrene as the parent nucleus, and has a similar skeleton to corticosteroids.
  • the specific structural formula is as follows:
  • the purity of the ergosterol monomer is preferably ⁇ 99%. There is no strict requirement on the source, regular purchase is sufficient.
  • the dosage form of the drug is preferably a medically acceptable dosage form; the medically acceptable dosage form preferably includes any one of powder, injection, capsule, tablet and oral solution.
  • the inducement of gastric ulcer preferably includes alcohol and/or acid; the alcohol is preferably anhydrous ethanol; and the acid is preferably acetic acid.
  • the ergosterol of the present invention has a similar skeleton to corticosteroids, the effects of ergosterol and corticosteroids are different: corticosteroids increase gastric acid secretion, inhibit gastric mucus secretion, and promote the occurrence of gastric ulcers; ergosterol can promote the secretion of gastric mucus, resist gastric ulcers caused by anhydrous ethanol, and promote the recovery of experimental gastric ulcers caused by acetic acid. Ergosterol can effectively prevent and treat gastric ulcers.
  • the results of the embodiment show that according to the dosage of 10-40 mg ergosterol/kg mouse and 50-500 mg ergosterol/d/person, gastric ulcers can be effectively prevented and treated.
  • the present invention also provides a drug for preventing and treating gastric ulcers, wherein the active ingredient of the drug includes ergosterol.
  • the ergosterol of the present invention also includes a drug with the function of preventing and treating gastric ulcers, which is composed of ergosterol as a raw material and an auxiliary material or auxiliary component allowed in the drug.
  • the present invention has no strict requirements on the specific type of the auxiliary material, and it can be selected according to the conventional dosage form of the drug.
  • Ergosterol purchased from McLean
  • lansoprazole purchased from Jiangsu Renhe Pharmaceutical Co., Ltd.
  • 48 SD healthy rats 200-220 g (purchased from Zhuhai Baishitong Biotechnology Co., Ltd.); 36 C57BL/6 healthy mice, 18-22 g (purchased from Guangzhou Ruige Biotechnology Co., Ltd.).
  • the healthy rats in step 1 were randomly divided into a control group, a model group, a lansoprazole group, a low-dose ergosterol group, a medium-dose ergosterol group, and a high-dose ergosterol group, with 8 healthy rats in each group.
  • the rats were given medication according to the method in Table 1. During the medication period, the diet, drinking water and other conditions of the rats in each group were the same.
  • the drugs were continuously administered for 7 days according to Table 1.
  • the rats in the model group, lansoprazole group, low-dose ergosterol group, medium-dose ergosterol group, and high-dose ergosterol group were gavaged with 1 mL of anhydrous ethanol; the rats in the control group were gavaged with 1 mL of purified water.
  • the rats were killed by overdose anesthesia, and the gastric tissues of the rats were obtained and dissected to observe the ulcers in the gastric tissues of the rats.
  • the ulcer area was calculated by grading using ImageJ. The results are shown in Figure 1 and Table 2.
  • the healthy mice in step 1 were randomly divided into a control group and an experimental group, with 6 healthy mice in the control group and 30 healthy mice in the experimental group.
  • the abdominal cavity of the control group was opened and randomly closed without treatment; the abdominal cavity of the experimental group was opened to expose the whole stomach, and acetic acid was dipped into a 2 mm diameter glass capillary, which was then poked into the stomach body for a total of 20 seconds.
  • the abdominal cavity was closed after waiting for 1 minute. After the stomach was opened, a whitish ulcer surface could be seen, indicating that the gastric ulcer model was successfully constructed.
  • mice On the second day after the model was established, the experimental mice were randomly divided into 5 groups, namely, model group, lansoprazole group, low-dose ergosterol group, medium-dose ergosterol group and high-dose ergosterol group, with 6 mice in each group.
  • the drugs were administered according to the method in Table 3. During the drug administration period, the diet, drinking water and other conditions of each group of rats were the same.
  • mice in each test group were killed, and the gastric tissues of the mice were obtained and dissected to observe the ulcers in the gastric tissues of the mice.
  • the ulcer area was calculated by grading using ImageJ. The results are shown in Figure 2 and Table 4.
  • mice in the control group had no gastric ulcers, while the model group had large-area gastric ulcers, indicating that the model was successfully constructed.
  • Lansoprazole administration for 3 days did not significantly reduce the ulcer area, while high, medium and low doses of ergosterol could significantly repair gastric ulcers caused by acetic acid and effectively treat gastric ulcers.
  • the Glide software was used to study the docking of the compound ergosterol with the RoR ⁇ protein, and the results were compared with the RoR ⁇ /Cholesterol cocrystal results.
  • Molecular docking of ergosterol and RoR ⁇ protein was performed, and the results are shown in Figure 3.
  • a in Figure 3 is the binding mode of RoR ⁇ with the substrate small molecule Cholesterol (cholesterol) (PDBID: 1N83), and B is the binding mode of RoR ⁇ with the substrate small molecule Ergosterol.
  • the left picture in A and B is the overall view, and the right picture is a partial view.
  • the orange stick is a small molecule
  • the blue cartoon is a protein
  • the green dotted line represents the water bridge effect
  • the gray dotted line represents the hydrophobic effect.
  • the root mean square deviation of molecular dynamics simulation can reflect the movement process of the complex.
  • the binding stability of RoR ⁇ protein and ergosterol was predicted using Amber18 software, and the results are shown in Figure 4.

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  • Health & Medical Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Epidemiology (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Organic Chemistry (AREA)
  • Steroid Compounds (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicinal Preparation (AREA)

Abstract

La présente invention appartient au domaine technique des médicaments biologiques, et concerne spécifiquement l'utilisation d'ergostérol dans la préparation d'un médicament pour la prévention et le traitement d'ulcères gastriques. L'ergostérol de la présente invention peut favoriser la sécrétion de mucus gastrique, résister aux ulcères gastriques provoqués par l'alcool éthylique absolu, favoriser la rééducation des ulcères gastriques provoqués par l'acide acétique, et prévenir et traiter efficacement les ulcères gastriques.
PCT/CN2023/123828 2022-10-10 2023-10-10 Utilisation d'ergostérol dans la préparation d'un médicament pour la prévention et le traitement d'ulcères gastriques WO2024078507A1 (fr)

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CN202211239995.8 2022-10-10
CN202211239995.8A CN115531393A (zh) 2022-10-10 2022-10-10 麦角甾醇在制备防治胃溃疡药物中的应用

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CN115531393A (zh) * 2022-10-10 2022-12-30 深圳市中医院 麦角甾醇在制备防治胃溃疡药物中的应用

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN102552284A (zh) * 2011-12-13 2012-07-11 陕西师范大学 麦角甾醇在制备肿瘤多药耐药逆转药物中的应用
CN109820954A (zh) * 2019-03-29 2019-05-31 湖南新汇制药股份有限公司 一种中药组合物、制备方法及其在制备治疗慢性非萎缩性胃炎药物上的用途
CN113509496A (zh) * 2021-07-29 2021-10-19 麦艳珍 一种假芝提取物及其制备方法和应用
CN115531393A (zh) * 2022-10-10 2022-12-30 深圳市中医院 麦角甾醇在制备防治胃溃疡药物中的应用

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN102552284A (zh) * 2011-12-13 2012-07-11 陕西师范大学 麦角甾醇在制备肿瘤多药耐药逆转药物中的应用
CN109820954A (zh) * 2019-03-29 2019-05-31 湖南新汇制药股份有限公司 一种中药组合物、制备方法及其在制备治疗慢性非萎缩性胃炎药物上的用途
CN113509496A (zh) * 2021-07-29 2021-10-19 麦艳珍 一种假芝提取物及其制备方法和应用
CN115531393A (zh) * 2022-10-10 2022-12-30 深圳市中医院 麦角甾醇在制备防治胃溃疡药物中的应用

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
SATOH, KANAKO ET AL.: "The Effects of Kampo-Formulation and the Constituting Crude Drugs, Prescribed for the Treatment of Peptic Ulcer on H,K-ATPase Activity", YAKUGAKU ZASSHI : JOURNAL OF THE PHARMACEUTICAL SOCIETY OF JAPAN, PHARMACEUTICAL SOCIETY OF JAPAN, vol. 121, no. 2, 31 December 2001 (2001-12-31), pages 173 - 178, XP009553930, ISSN: 0031-6903 *

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