CN112656938B

CN112656938B - Application of ginsenoside Re and lysozyme in preparation of medicine for treating or preventing abdominal aortic aneurysm

Info

Publication number: CN112656938B
Application number: CN202110162627.7A
Authority: CN
Inventors: 黄芸; 佟苗苗; 王娜; 赵丽丽; 史梦召; 吴雨; 甘晓若
Original assignee: Hebei Medical University
Current assignee: Hebei Medical University
Priority date: 2021-02-05
Filing date: 2021-02-05
Publication date: 2022-12-06
Anticipated expiration: 2041-02-05
Also published as: CN112656938A

Abstract

The invention relates to ginsenoside Re and application of ginsenoside Re and lysozyme in preparation of a medicine for treating or preventing abdominal aortic aneurysm.

Description

Application of ginsenoside Re and lysozyme in preparation of medicine for treating or preventing abdominal aortic aneurysm

Technical Field

The invention belongs to the field of medicines, and particularly relates to application of ginsenoside Re and lysozyme in preparation of a medicine for treating or preventing abdominal aortic aneurysm.

Background

Abdominal Aortic Aneurysm (AAA) is a serious cardiovascular disease, manifested as degenerative disease in which the abdominal aortic wall structure is destroyed, thereby progressively expanding into a pulsatile mass with a diameter exceeding 1.5 times the normal diameter, with a mortality rate of up to 80% once the tumor mass has ruptured. The main disease population of abdominal aortic aneurysm is the elderly patients, the incidence rate of which is 5 times that of women in men and up to 8% in men over 65 years old, which is a significant cause of death in elderly men. The abdominal aortic aneurysm is caused by inflammation on the wall of the artery, and the infiltration of inflammatory cells causes the transformation of vascular smooth muscle cells from a contraction phenotype to an inflammation phenotype, and stimulates protease-mediated extracellular matrix degradation to cause the apoptosis of the vascular smooth muscle cells and the remodeling of the artery wall, so that the arterial vessel wall is gradually expanded to form the aneurysm. The current inspection technology can find early abdominal aortic aneurysm, but the treatment of the abdominal aortic aneurysm lacks effective therapeutic drugs. For patients with aneurysms that do not meet the surgical requirements (diameter < 5.5 cm and growth rate is not rapid), there is no effective treatment other than close monitoring of the aneurysm diameter.

Panax notoginseng is the dried root and rhizome of Panax notoginseng (Burk.) F.H. Chen of Araliaceae, and the traditional medicine considers that Panax notoginseng saponins have the functions of activating blood circulation, removing blood stasis, dredging collaterals and activating collaterals, are widely used for treating cardiovascular and cerebrovascular diseases, are important medicinal resources in China, and are also approved by Wei Ji to be articles for health food. The saponin is active ingredient of Notoginseng radix root or rhizome, and mainly contains Notoginseng radix saponin R1, ginsenoside Rgl, ginsenoside Re, ginsenoside Rb1, ginsenoside Rd, etc. Wherein ginsenoside Re is used as a main effective component in Notoginseng radix total saponin, and has protective effect on myocardial ischemia, myocardial apoptosis and arrhythmia.

The national health committee of the people's republic of china, as early as 2010, has published a food additive that allows lysozyme to be used as a food additive. In the medical field, lysozyme is found to be an important immune factor widely existing in various tissues of human bodies, has the effects of promoting the repair of damaged tissues of the bodies, correcting the immune activation degree, reducing acute inflammatory reaction and the like, and particularly has better curative effects on the aspects of burn wound infection, herpes treatment and the like. We found that lysozyme can be combined with many natural small molecule compounds non-specifically and can increase the bioactivity of natural small molecules. After the small-dose lysozyme is combined with baicalein, baicalin and scutellarin, the antibacterial activity of the lysozyme and the scutellarin is greatly improved; after the combination of the small dose of lysozyme and caffeine, the inhibition effect of caffeine on liver cancer HepG2 cells is obviously enhanced. The Hoechst 33342 staining analysis shows that the combined application of caffeine and small doses of lysozyme promotes the apoptosis of HepG2 cells.

At present, no relevant report is found on the combined use of the ginsenoside Re and lysozyme for treating and preventing the abdominal aortic aneurysm.

Disclosure of Invention

One of the purposes of the invention is to provide the application of the ginsenoside Re and lysozyme in the preparation of the medicine for treating and/or preventing abdominal aortic aneurysm.

As some preferred embodiments of the invention, the molar ratio of the ginsenoside Re to the lysozyme is 1 to 1.

As some preferred embodiments of the present invention, the medicament is formulated as one of the following: tablets, capsules, granules, powders, suspensions, emulsions, powders, solutions, gels, syrups, pills, tinctures, vinuses, ointments, lozenges, mixtures, suppositories, injections, inhalants or sprays.

The invention also aims to provide a medicament for preventing and/or treating abdominal aortic aneurysm, which comprises ginsenoside Re and lysozyme as active ingredients.

As some preferred embodiments of the present invention, further comprising at least one pharmaceutically acceptable carrier or excipient.

For pharmaceutical preparations, the ginsenoside and lysozyme combination may be administered independently or in combination with pharmaceutically acceptable carriers and excipients. "pharmaceutically acceptable carriers or excipients" include: diluents, fillers, binders, disintegrants, lubricants, glidants, granulating agents, coating agents, wetting agents, solvents, co-solvents, suspending agents, emulsifiers, sweeteners, flavoring agents, taste masking agents, colorants, anti-caking agents, humectants, chelating agents, plasticizers, tackifiers, antioxidants, preservatives, stabilizers, surfactants, and buffers, it will be understood by those skilled in the art that certain pharmaceutically acceptable excipients may be used in more than one function and in alternative functions depending on how much of the excipient is present in the formulation and what other ingredients are present in the formulation. There are many sources available to those skilled in the art which describe pharmaceutically acceptable excipients and which can be used to select suitable pharmaceutically acceptable excipients, for example, books by the Remington pharmaceutical university, the annual book of Chinese pharmacy, the pharmacy, etc.

The technical scheme of the invention has the following beneficial effects: the ginsenoside Re and the lysozyme can be used together to treat and prevent the abdominal aortic aneurysm, and experiments prove that the ginsenoside Re has an obvious inhibiting effect on the mouse lower abdominal aortic aneurysm, can effectively inhibit the growth of the mouse lower abdominal aortic aneurysm and delay the progress of the abdominal aortic aneurysm.

Drawings

Fig. 1 is a diagram of abdominal aorta of each group, in which: a is blank control group; b is a model control group; c is ginsenoside Re group; d is a ginsenoside Re-lysozyme combination group (12;

FIG. 2 is a graph of the relative values of the diameters of the lower abdominal aorta, in which: a is blank control group; b is a model control group; c is lysozyme group; d is ginsenoside Re group; e is ginsenoside Re-lysozyme combined group; * P < 0.05, compared to blank; # P < 0.05, compared to the model control group.

Detailed Description

In order to make the objects, technical solutions and advantages of the present invention more apparent, the present invention will be described in detail and fully with reference to the following embodiments.

Example 1 study of drug efficacy in inhibiting abdominal aortic aneurysm

1. Establishment of abdominal aortic aneurysm model

Experimental animals C57B/6J mice, 12 weeks, SPF grade, male, 20 body mass soil 2g, purchased from the Experimental animals center of Hebei medical university.

The mice are raised in an SPF animal room, the humidity is kept at 50-60%, and the temperature is kept at 22-24 ℃. The illumination period is 7. Under sterile environment, anesthetizing 10% chloral hydrate under abdominal skin of mouse, disinfecting abdominal skin by conventional skin preparation, cutting iliac crest at two sides with ophthalmologic scissors, making a 1.5cm incision towards head side, cutting peritoneum deeply, widening visual field, exposing abdominal aorta, separating two sides of artery carefully, stripping off abdominal aorta at iliac artery and renal artery branch, placing cut waterproof film under abdominal aorta, placing small water-absorbing material above the film, and making the water-absorbing material slightly smallerIn the waterproof film, the water-absorbing material is put in 0.5mol/L CaCl ₂ Wrapping and externally applying, taking out the water absorbing material, the waterproof film and the sterile gauze in sequence after 15 min, sucking the residual liquid, flushing the abdominal cavity with sterile normal saline, and ligating bleeding points. And (4) performing surgical suture, respectively suturing the peritoneal layer and the skin layer, and placing the anesthetized mouse in a lateral lying position. After operation, 7 days later, the heart apex of the mouse is perfused, the abdominal aorta is taken, the diameter of the abdominal aorta at the lower end of the kidney is measured, and the abdominal aortic aneurysm model is determined to be successful by 50% amplification compared with the diameter of the abdominal aorta at the lower end of the kidney of the blank mice.

2. Treatment regimens

The mice are divided into five groups, 5 model control groups/group, 5 experimental groups/group (three groups, each group is a lysozyme group and a ginsenoside Re group, and the ginsenoside Re-lysozyme (molar ratio 12. The model control group and the experimental group are respectively molded according to the method, and after operation, the model control group is perfused with the normal saline, the administration dosage of the experimental group is 50 mg/kg/day, and the treatment lasts for 14 days. Perfusing the apex of the heart of the mouse, taking the abdominal aorta, measuring the diameter of the abdominal aorta at the lower end of the kidney, and respectively recording the diameters of the abdominal aorta under the kidney of the mouse in a blank control group, a model control group and an experimental group. The average value of the blank control group is used as a standard value 1.

3. Results

As can be seen from fig. 1, the combination of the ginsenoside Re group and the ginsenoside Re-lysozyme (12) significantly reduced abdominal aortic aneurysm compared with the model control group, and the combination of the ginsenoside Re and the ginsenoside Re-lysozyme (12) can effectively inhibit the growth of abdominal aortic aneurysm of mice.

The results are shown in fig. 2 and table 1 by measuring the diameters of infrarenal abdominal aorta of each group of mice:

TABLE 1 Effect on the diameter of the lower abdominal aorta

Group of	n	Relative value of abdominal aorta diameter
			Blank space	5	1±0.01
Model control group	5	2.01±0.10*
			Lysozyme group	5	1.89±0.05*
Ginsenoside Re	5	1.30±0.04#
			Ginsenoside Re + lysozyme (12	5	1.130±0.02#※

* P < 0.05, compared to blank; # P < 0.05, compared to model control; in addition, P is less than 0.05, compared with ginsenoside Re group

The results show that the ginsenoside Re-lysozyme (12) combined group has obvious difference compared with the ginsenoside Re group and the model control group, and the ginsenoside Re-lysozyme combined group has obvious inhibition effect on the expansion of abdominal aortic aneurysm of mice.

Finally, it should be noted that: the above examples are only intended to illustrate the technical solution of the present invention, but not to limit it; although the present invention has been described in detail with reference to the foregoing embodiments, it will be understood by those of ordinary skill in the art that: the technical solutions described in the foregoing embodiments may still be modified, or some technical features may be equivalently replaced; and such modifications or substitutions do not depart from the spirit and scope of the corresponding technical solutions of the embodiments of the present invention.

Claims

1. The ginsenoside Re and lysozyme are used in combination for preparing the medicine for treating abdominal aortic aneurysm, and the molar ratio of the ginsenoside Re to the lysozyme is 12.

2. The use of claim 1, wherein the medicament is in a dosage form of one of: tablets, capsules, granules, powders, syrups, injections, inhalants or sprays.