WO2023206378A1 - Utilisation de cordycépine dans la préparation de produit pour soulager la pression - Google Patents

Utilisation de cordycépine dans la préparation de produit pour soulager la pression Download PDF

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Publication number
WO2023206378A1
WO2023206378A1 PCT/CN2022/090346 CN2022090346W WO2023206378A1 WO 2023206378 A1 WO2023206378 A1 WO 2023206378A1 CN 2022090346 W CN2022090346 W CN 2022090346W WO 2023206378 A1 WO2023206378 A1 WO 2023206378A1
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cordycepin
mice
stress
pharmaceutical composition
test
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PCT/CN2022/090346
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English (en)
Chinese (zh)
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景晓源
刘欣安
洪丰
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中国科学院深圳先进技术研究院
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Priority to PCT/CN2022/090346 priority Critical patent/WO2023206378A1/fr
Publication of WO2023206378A1 publication Critical patent/WO2023206378A1/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
    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
    • A61K31/7042—Compounds having saccharide radicals and heterocyclic rings
    • A61K31/7052—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides
    • A61K31/706—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom
    • A61K31/7064—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom containing condensed or non-condensed pyrimidines
    • A61K31/7076—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom containing condensed or non-condensed pyrimidines containing purines, e.g. adenosine, adenylic acid
    • 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
    • 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
    • A61P3/04—Anorexiants; Antiobesity agents

Definitions

  • the present invention relates to the field of biotechnology, and in particular to the use of cordycepin in the preparation of stress-relieving products.
  • Cordyceps sinensis In the 1950s, wild Cordyceps militaris was discovered in the Changbai Mountain area of Jilin. Studies have confirmed that its ingredients are far more effective than wild Cordyceps sinensis, so it was named Cordyceps sinensis. In 1951, German scientist Cunningham et al. first discovered the core component of Cordyceps militaris, "cordycepin", and discovered its It has a variety of pharmacological activities such as antibacterial, anti-inflammatory, antiviral, anti-tumor and immunomodulation. In the following decades, the academic community carried out a large number of in-depth research on cordycepin.
  • cordycepin in Phase III Clinical trials are used to treat patients with acute pre-B and pre-T lymphocytic leukemia; in 2017, Professor Wang Chengshu of the Chinese Academy of Sciences published the latest research results on cordycepin online in the Cell sub-journal Cell Chemical Biology: This study completely analyzed the role of cordycepin in The biosynthetic mechanism in Cordyceps militaris, and it was also discovered for the first time that Cordyceps militaris can synthesize the anti-cancer drug Pentostatin. This compound is used to protect the structural stability of the synthesized cordycepin.
  • cordycepin has biological activities such as lung and kidney protection, anti-three highs, anti-tumor, neuroprotection, anti-inflammatory, antioxidant and immune regulation.
  • cordycepin is mostly injected into mice through intraperitoneal injection. This method has a relatively large impact on the mice, and the injection is done after the mice have undergone pressure stress, so only the therapeutic effect of cordycepin can be evaluated.
  • Non-patent literature 1 Wang Linfeng, Liu Ruyi, Yang Gaiqing, Zhu Heshui, Yueying, Han Liqiang, Jia Shaodan, Yang Guoyu. Effects of melatonin on growth, fat metabolism and distribution in rats [J]. Journal of Animal Nutrition, 2015, 27(8): 2456-2465.
  • the present invention provides the use of cordycepin in preparing products for relieving stress.
  • the present invention provides the use of cordycepin in the preparation of stress-relieving products; the use is for distributing abnormal body fat.
  • the abnormal body fat is abnormal body fat caused by stress.
  • the effective concentration of cordycepin in the product is 25 mg/kg.
  • the products include medicines, foods and health care products.
  • the drug is an oral formulation.
  • a pharmaceutical composition for relieving stress includes cordycepin.
  • the cordycepin is the only active ingredient.
  • the pharmaceutical composition further includes pharmaceutically acceptable auxiliary ingredients.
  • the present invention conducts a stress stress test on mice administered with cordycepin for four weeks to evaluate the impact of cordycepin on the mice's ability to withstand stress.
  • cordycepin By weighing the mice's circumference, the changes in the mice's weight are observed, and the mice are explored Distribution and changes in body fat.
  • Figure 1 is a diagram of the test results of 4 days of pressure stress in mice in Example 2 after undergoing intragastric administration of cordycepin for 4 consecutive weeks.
  • Figure 2 is a graph showing the results of weighing the mice every week and recording the weight change trend of the mice in Example 3.
  • Figure 3 is a graph showing the results of weighing the fat weight of mice and analyzing the obesity rate in Example 4.
  • mice SPF grade C57BL/6J male mice, 7 weeks old, provided by Zhejiang Weitong Lihua Experimental Animal Technology Co., Ltd. Experimental animals are raised in a barrier environment of an SPF-grade animal room. The temperature and relative humidity ranges within the barrier are 20°C to 26°C and 40% to 70% respectively. The lighting is switched off 12h: 12h day and night to ensure free access to adequate feed and water. This experiment applied for ethical approval for animal experimentation. All mouse tissue collection work was performed after anesthesia with injection of pentobarbital sodium (50mg/kg) and then sacrificed by cervical dissection. According to the experimental requirements, the mice were randomly divided into 50 groups, with 10 mice in each group.
  • mice were administered cordycepin by gavage, and a control group was set up and fed the same amount of water.
  • Cordycepin was purchased from Shenzhen Chenlu Biotechnology Co., Ltd. Among them, the cordycepin gavage group of mice was set with a dose of 12.5 mg/kg and a 25 mg/kg group according to the weight of the mice.
  • the cordycepin used for gavage was an aqueous solution of cordycepin, and the corresponding dose concentration was set to 1.25 mg. /mL and 2.5mg/mL; mice received continuous gavage for 4 weeks, and the gavage volume of each mouse was 200uL (the weight of each mouse was approximately 20mg). After the gavage was completed, pressure stress stimulation was performed. .
  • mice will undergo a 4-day repeated stress test and receive the following stress stimuli every day, including (i) 1 hour in a restrained environment; (ii) 30 minutes of tail suspension ; (iii) Foot shock test lasting 2 minutes (0.5mA, 2s, 10s interval, 10 cycles).
  • mice 1.4 The above five groups of mice are as follows: water + non-stress group; water + stress group; 25 + non-stress group (cordycepin dose 25 mg/kg group); 25 + stress group (cordycepin dose 25 mg/kg group) ); 12.5+ stress group (cordycepin dose 12.5mg/kg group).
  • Example 2 Behavioral detection and analysis of anxiety and depression
  • the test site is a square box of 35cm ⁇ 35cm ⁇ 30cm.
  • the floor of the box (8.75cm ⁇ 8.75cm) is virtually divided into 16 quadrants, and the four middle quadrants are designated as the center. area, the central area size is 17.5 ⁇ 17.5cm.
  • the mice were randomly placed in the central area of the open field box and allowed to explore for 10 minutes. The time the mice stayed in the central area was counted and used to evaluate the anxiety index. The longer the mice stayed in the central area, the worse the mice were. The anxiety level is lower.
  • Figure 1A and B In the open field test, when mice were administered 12.5 mg/kg of cordycepin, the total moving distance of the mice was reduced, and the mice's anxiety level was significantly reduced.
  • Elevated plus maze experiment The elevated plus maze (EPM) device is a square maze, consisting of two closed arms (35cm ⁇ 5cm, 15cm high) and two open arms (35cm ⁇ 5cm, 15cm high) fixed on a 5cm ⁇ 5cm square with open center.
  • the maze is 50cm above the ground.
  • the mouse was placed in the center of the maze, facing the open arm.
  • the time spent in the open arm was counted and used as an anxiety index. The longer the arms were open, the less anxious the mice were.
  • the test results are shown in Figure 1C, D: In the elevated plus maze test, when mice were administered 12.5 mg/kg of cordycepin, the mice's residence time in the open arm was significantly increased, and the mice's anxiety level was significantly reduced.
  • Tail suspension test The tail suspension test (TST) is widely used to assess despair-like behavior in rodents. Hang the mouse 30cm above the ground with tape, which is placed about 2cm from the tip of the tail. The test lasts 6 minutes. During the last 5 minutes of the test, the duration of immobility (stop of struggling, only slight body movement) was automatically recorded. Time spent in a still state is measured and used as an indicator of depression. The longer the time spent in a resting state, the more depressed the mice became. The test results are shown in Figure 1E: When mice were orally administered 12.5 mg/kg of cordycepin, the mice's immobility time in the tail suspension test was significantly reduced, and the mice's anxiety level was significantly reduced.
  • Behavioral data statistics and analysis Behavioral videos were analyzed using visuTrack software to obtain quantitative indicators. Statistics were analyzed and graphed using GraphPad Prism 8.0 software. Data were expressed as Mean ⁇ SEM, and differences between groups were tested using One-way ANOVA. *p ⁇ 0.05, **p ⁇ 0.01, ***p ⁇ 0.001, ****p ⁇ 0.001 are used to evaluate the anxiety and depression state of mice.
  • mice in Example 1 were measured for weekly weight, and the change trend of the mouse weight was analyzed.
  • the results are shown in Figure 2: the weight gain trend of the stressed mice increased significantly, but the dosage was 12.5 mg. /kg and 25mg/kg of cordycepin slowed down the weight gain trend.
  • the results are shown in Figure 3: After taking 25 mg/kg of cordycepin, the obesity index increased significantly compared with the stressed mice, which improved the body fat loss in mice caused by stress and had a slowing effect on fat loss.

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Chemical & Material Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Obesity (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Organic Chemistry (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Hematology (AREA)
  • Diabetes (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Engineering & Computer Science (AREA)
  • Molecular Biology (AREA)
  • Epidemiology (AREA)
  • Child & Adolescent Psychology (AREA)
  • Medicines Containing Plant Substances (AREA)
  • Medicines Containing Material From Animals Or Micro-Organisms (AREA)

Abstract

Utilisation de cordycépine dans la préparation d'un produit pour soulager la pression. La cordycépine répartit une graisse corporelle anormale. Une composition pharmaceutique pour soulager la pression, la composition pharmaceutique comprenant de la cordycépine.
PCT/CN2022/090346 2022-04-29 2022-04-29 Utilisation de cordycépine dans la préparation de produit pour soulager la pression WO2023206378A1 (fr)

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PCT/CN2022/090346 WO2023206378A1 (fr) 2022-04-29 2022-04-29 Utilisation de cordycépine dans la préparation de produit pour soulager la pression

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PCT/CN2022/090346 WO2023206378A1 (fr) 2022-04-29 2022-04-29 Utilisation de cordycépine dans la préparation de produit pour soulager la pression

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Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN101574144A (zh) * 2008-05-07 2009-11-11 中国医学科学院药物研究所 3′-脱氧腺苷减肥、胰岛素增敏和改善脂代谢的用途
CN106798725A (zh) * 2015-11-26 2017-06-06 王春梅 一种虫草素纳米脂质体及其制备方法与抗肿瘤活性应用
CN106974928A (zh) * 2016-01-19 2017-07-25 上海国宝企业发展中心 虫草素及制剂在防治器官纤维化药物及健康产品中的用途
CN108117576A (zh) * 2016-11-26 2018-06-05 刘启乐 一种高效提取虫草素的提取方法
CN110801456A (zh) * 2019-12-13 2020-02-18 福建农林大学 虫草素在制备保肝产品中的应用

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN101574144A (zh) * 2008-05-07 2009-11-11 中国医学科学院药物研究所 3′-脱氧腺苷减肥、胰岛素增敏和改善脂代谢的用途
CN106798725A (zh) * 2015-11-26 2017-06-06 王春梅 一种虫草素纳米脂质体及其制备方法与抗肿瘤活性应用
CN106974928A (zh) * 2016-01-19 2017-07-25 上海国宝企业发展中心 虫草素及制剂在防治器官纤维化药物及健康产品中的用途
CN108117576A (zh) * 2016-11-26 2018-06-05 刘启乐 一种高效提取虫草素的提取方法
CN110801456A (zh) * 2019-12-13 2020-02-18 福建农林大学 虫草素在制备保肝产品中的应用

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