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CN-121975717-A - Application of gynostemma pentaphylla exosome in preparing medicament for protecting cardiac muscle

CN121975717ACN 121975717 ACN121975717 ACN 121975717ACN-121975717-A

Abstract

The application relates to the field of biological medicine, and discloses application of gynostemma pentaphylla exosomes in preparing medicaments for protecting cardiac muscle. The medicine comprises a medicine for treating myocardial injury after myocardial infarction, a medicine for improving myocardial cell dysfunction in sub-health state and a myocardial health care medicine. The application discovers the myocardial protection effect of the gynostemma pentaphylla exosome for the first time, and in a rat myocardial infarction reperfusion model, the gynostemma pentaphylla exosome remarkably inhibits and reduces apoptosis and down regulates alpha-SMA expression, and blocks myocardial deterioration process. The recovery effect on heart function is equivalent to that of small molecular medicine trimetazidine and is obviously better than that of gynostemma pentaphylla saponin.

Inventors

  • CHEN QIYING
  • ZHANG YANAN

Assignees

  • 复旦大学附属华山医院
  • 上海开宝智远生物科技有限公司

Dates

Publication Date
20260505
Application Date
20260317

Claims (10)

  1. 1. The extraction method of the gynostemma pentaphylla exosome is characterized by comprising the following steps: step 1, taking fresh gynostemma pentaphylla leaves, cleaning, disinfecting, sterilizing and drying; step 2, mixing the gynostemma pentaphylla leaves treated in the step 1 with sodium chloride, sealing and standing, collecting exudates, and then carrying out desalting treatment to obtain dialysate; step 3, the dialyzate obtained in the step 2 is filtered by 0.8 mu m,0.45 mu m and 0.22 mu m in sequence to obtain filtrate; and 4, centrifuging the filtrate obtained in the step 3, taking supernatant, and further centrifuging the supernatant to obtain precipitate, namely the gynostemma pentaphylla exosome.
  2. 2. The extraction method according to claim 1, wherein the specific steps in the step 4 are that the filtrate obtained in the step 3 is centrifuged at 4 ℃ for 30min at 2,000g, the supernatant is taken, the supernatant is transferred into a new centrifuge tube, and the supernatant is centrifuged at 100,000g for 120min at 4 ℃ to obtain the precipitate as gynostemma pentaphylla exosomes.
  3. 3. The gynostemma pentaphylla exosome obtained by the extraction method of claim 1 or 2.
  4. 4. Use of the gynostemma pentaphylla exosome of claim 3 in the preparation of a medicament for myocardial protection.
  5. 5. The use according to claim 4, wherein the medicament comprises: A medicament for treating myocardial injury after myocardial infarction; A medicament for ameliorating cardiomyocyte dysfunction in a sub-healthy state; Myocardial health care medicine.
  6. 6. A pharmaceutical composition comprising an effective amount of the gynostemma pentaphylla exosome of claim 3 and a pharmaceutically acceptable carrier or adjuvant.
  7. 7. The pharmaceutical composition of claim 6, wherein the pharmaceutical composition further comprises a permeation enhancer.
  8. 8. The pharmaceutical composition according to claim 6 or 7, wherein the dosage form of the pharmaceutical composition comprises a liquid filled hard capsule formulation, an oral suspension formulation and a sublingual drop formulation.
  9. 9. A sublingual drop formulation comprising an effective amount of the gynostemma pentaphylla exosome of claim 3 and an effective acting amount of the penetration enhancer menthol.
  10. 10. The sublingual drop formulation of claim 9, further comprising an effective amount of a thickening agent, a flavoring agent, and a preservative.

Description

Application of gynostemma pentaphylla exosome in preparing medicament for protecting cardiac muscle Technical Field The application relates to the field of biological medicine, in particular to the crossing field of natural medicine delivery and cardiovascular medicine, and more particularly relates to application of gynostemma pentaphylla exosomes in preparing medicines for protecting cardiac muscles. Background Traditionally, the drug effect of gynostemma pentaphylla is attributed to the saponin components (such as Gypenosides), and at present, the prior art reports the protection effect of gynostemma pentaphylla total glycosides and saponins on damaged myocardial cells, but the problems of low oral bioavailability, rapid metabolism, poor targeting and the like exist. Like animal cells, plant cells actively secrete 30-200 nm membranous nanovesicles containing specific mirnas, flavones, saponin precursors and antioxidase, with natural stability and trans-species biological activity, called Plant Exosomes or Plant Exosome-like nanovesicles (Plant Exosomes-like Nanoparticles, ELNs). The prior researches show that the plant exosome has great influence on physiological and pathological states of human bodies, for example, the ginger exosome can promote intestinal repair and the ginseng exosome can protect nerves. Up to now, no report on the application of gynostemma pentaphylla exosomes in cardiovascular diseases has been found. In addition, patients with myocardial infarction often suffer from gastrointestinal congestion and malabsorption, and the effect of oral drugs is limited. Traditional oral preparation has limited absorption and slow onset of action. Therefore, it is of great clinical importance to develop a myocardial protective formulation that can be rapidly activated and has high bioavailability. Disclosure of Invention The application aims to provide a plant exosome (gynostemma pentaphylla exosome) with myocardial protection activity, which is separated and extracted from gynostemma pentaphylla, and is applied to preparing a myocardial protection medicament, and further develops a sublingual administration dosage form of the medicament. In order to achieve the above object, the present application adopts the following technical scheme: in a first aspect, the application provides a method for extracting gynostemma pentaphylla exosomes, comprising the following steps: step 1, taking fresh gynostemma pentaphylla leaves, cleaning, disinfecting, sterilizing and drying; step 2, mixing the gynostemma pentaphylla leaves treated in the step 1 with sodium chloride, sealing and standing, collecting exudates, and then carrying out desalting treatment to obtain dialysate; step 3, the dialyzate obtained in the step 2 is filtered by 0.8 mu m,0.45 mu m and 0.22 mu m in sequence to obtain filtrate; and 4, centrifuging the filtrate obtained in the step 3, taking supernatant, and further centrifuging the supernatant to obtain precipitate, namely the gynostemma pentaphylla exosome. Further, the specific steps in the step 4 are that the filtrate obtained in the step 3 is centrifuged at 4 ℃ for 30min at 2,000g, the supernatant is taken, the supernatant is transferred into a new centrifuge tube, and the supernatant is centrifuged at 100,000g for 120min at 4 ℃ to obtain sediment which is gynostemma pentaphylla exosome. In a second aspect, the present application provides a gynostemma pentaphylla exosome obtained by the extraction method. In a third aspect, the application provides an application of the gynostemma pentaphylla exosome in preparing a medicament for protecting cardiac muscle. Further, the medicament comprises: A medicament for treating myocardial injury after myocardial infarction; A medicament for ameliorating cardiomyocyte dysfunction in a sub-healthy state; Myocardial health care medicine. In a fourth aspect, the application provides a pharmaceutical composition comprising an effective dose of said gynostemma pentaphylla exosomes, together with a pharmaceutically acceptable carrier or adjuvant. Further, the pharmaceutical composition further comprises a penetration enhancer. Further, the dosage forms of the pharmaceutical composition include liquid filled hard capsule formulations, oral suspension formulations, and sublingual drop formulations. In a fifth aspect, the present application provides a sublingual drop formulation comprising an effective amount of said gynostemma pentaphylla exosomes, and an effective acting amount of the penetration enhancer menthol. Further, it includes an effective amount of a thickener, a flavoring agent, and a preservative. In summary, the application has the following beneficial effects: 1. Full-cycle myocardial protection mechanism. Unlike the chemical drug Trimetazidine (TMZ) or gypenosides, the gynostemma pentaphylla exosomes of the present invention naturally carry a variety of bioactive molecules. In the rat myocardial infarction reperfusion model, gynostemma pentaphy