CN104758304B

CN104758304B - Medical application of notoginsenoside R1

Info

Publication number: CN104758304B
Application number: CN201410002633.6A
Authority: CN
Inventors: 王峥涛; 张二云; 高波; 黄玲芳; 杨莉; 吴晓俊
Original assignee: Shanghai University of Traditional Chinese Medicine
Current assignee: Shanghai University of Traditional Chinese Medicine
Priority date: 2014-01-03
Filing date: 2014-01-03
Publication date: 2019-12-13
Anticipated expiration: 2034-01-03
Also published as: CN104758304A

Abstract

The invention relates to the field of medicine and pharmacology, and in particular relates to medical application of notoginsenoside R1. Animal experiments prove that the notoginsenoside R1 can effectively promote the wound healing of diabetes, which has great significance for the treatment of diabetic gangrene.

Description

Medical application of notoginsenoside R1

Technical Field

The invention relates to the field of medical health products, in particular to a medical application of notoginsenoside R1.

Background

Diabetes mellitus is a metabolic disease seriously threatening human health, and has become the fourth disease causing death after cardiovascular disease, tumor and AIDS. Statistical data show that there are 2.85 million diabetics in the world currently, and it is predicted that 4.39 million diabetics will reach 2030 worldwide, and complications caused by diabetes become the main cause of disability and death for the patients. Among the many complications of diabetes, impaired wound healing in diabetics is a typical complication of diabetes, and if chronic injuries and ulcers occur on feet, diabetic feet can be caused, and serious patients even cause amputation, which is the disease with the highest hospitalization rate of diabetics, and one amputation caused by diabetes is reported every 30 seconds all over the world. However, there is no effective treatment to date.

In the case of diabetic patients, when blood sugar is too high, dehydration may occur both inside and outside cells, which may affect wound healing. Meanwhile, the blood sugar of the diabetic is not well controlled, and the capability of the organism to kill bacteria is reduced. Hyperglycemia reduces the ability of cells to transport oxygen to tissues, causes poor blood circulation, and also affects wound healing. Elevated blood glucose can easily cause microangiopathy, damage blood vessels and nerves, and make ulcer healing difficult.

Therefore, the search for therapeutic agents capable of promoting the healing of diabetic wounds has been one of the hot spots of research in the field of diabetes.

Notoginsenoside R1 (Notogenoside R1) is a natural saponin compound, and is mainly present in Notoginseng radix. Research shows that the notoginsenoside has the functions of reducing blood fat, resisting tumor, eliminating oxygen radical, resisting oxidation, etc.

Disclosure of Invention

The invention aims to provide a new medical application of notoginsenoside R1.

Specifically, the invention provides an application of notoginsenoside R1 in preparing a composition for obviously promoting epidermis regeneration and granulation tissue formation.

Specifically, the invention provides an application of notoginsenoside R1 in preparing a composition for shortening wound healing time.

Specifically, the invention provides an application of notoginsenoside R1 in preparing a composition for promoting wound healing of a diabetic patient.

Specifically, the invention provides an application of notoginsenoside R1 in preparing a composition for treating diabetic foot.

In particular, the invention provides application of notoginsenoside R1 in preparing a composition for preventing wounds of diabetic patients from being difficult to heal. .

in particular to the application of the notoginsenoside R1 in preparing medicines, foods, cosmetics, washing products or toothpaste for preventing wounds of diabetes patients from being difficult to heal.

Specifically, the invention provides application of notoginsenoside R1 in preparation of a medicament or food for preventing diabetic foot.

Specifically, the invention provides an application of notoginsenoside R1 in preparing a composition for treating or preventing diabetic gangrene. .

specifically, the invention provides application of notoginsenoside R1 in preparation of drugs or foods or cosmetics or washing products or toothpaste for preventing diabetic gangrene.

The details of various aspects of the invention are set forth in subsequent sections. The features, objects, and advantages of the invention will be apparent from the description and from the claims.

Drawings

FIG. 1 is a graph showing the effect of R1 on wound healing in db/db mice;

FIG. 2 is a graph showing the effect of R1 on the mean days to healing of wounds in db/db mice;

Figure 3 demonstrates that the average healing days for R1 is significantly better than the blank control group;

Detailed Description

The invention arose in part from the unexpected discovery that: the notoginsenoside R1 can obviously promote the regeneration of epidermis and the formation of granulation tissue, obviously shorten the time of wound healing and effectively promote the wound healing of diabetes. Therefore, the notoginsenoside R1 can be used for healing chronic wounds such as diabetic feet.

furthermore, the invention provides application of the notoginsenoside R1 in preparing a medicament or food for treating diabetic wound healing.

The molecular formula of the notoginsenoside R1 is as follows: c₄₇H₈₀O₁₈The molecular weight is: 933.13, having the formula:

R=Glc R₁=H R₃=OR₂;

R₂=Xy¹-²Glc-

notoginsenoside R1 of the present invention is commercially available from Sigma chemical, shanghai-lin biotechnology limited, and the like.

The notoginsenoside R1 of the invention is prepared into a medicament as an example. The notoginsenoside R1 of the present invention can be used alone or in the form of a pharmaceutical composition. The pharmaceutical composition comprises the notoginsenoside R1 of the invention as an active ingredient and a pharmaceutically acceptable carrier. Preferably, the pharmaceutical composition of the present invention contains 0.1 to 99.9% by weight of notoginsenoside R1 of the present invention as an active ingredient. The pharmaceutical carrier does not damage the pharmaceutical activity of the notoginsenoside R1, and the effective dosage of the notoginsenoside R1 is nontoxic to human body.

Such pharmaceutically acceptable carriers include, but are not limited to: lecithin, aluminum stearate, alumina, ion exchange materials, self-emulsifying drug delivery systems, tweens or other surfactants, serum proteins, buffer substances such as phosphates, glycine, sorbic acid, water, salts, electrolytes such as protamine sulfate, disodium hydrogen phosphate, potassium hydrogen phosphate, sodium chloride, zinc salts, magnesium silicate, mixtures of saturated fatty acid partial glycerides, and the like.

Other conventional pharmaceutical adjuvants such as binder (e.g. microcrystalline cellulose), filler (e.g. starch, glucose, anhydrous lactose and lactose beads), disintegrant (e.g. crosslinked PVP, croscarmellose sodium, low-substituted hydroxypropylcellulose), lubricant (e.g. magnesium stearate), and absorption enhancer, adsorption carrier, flavoring agent, sweetening agent, excipient, diluent, wetting agent, etc.

Notoginsenoside R1 and pharmaceutical compositions thereof of the present invention can be prepared according to conventional methods in the art and can be administered by enteral or parenteral or topical routes. The oral preparation comprises capsule, tablet, oral liquid, granule, pill, powder, pellet, and unguent; parenteral preparations include injections and the like; topical preparations include creams, patches, ointments, sprays, and the like. Oral formulations are preferred.

The administration route of the notoginsenoside R1 and the pharmaceutical composition thereof can be oral, sublingual, transdermal, intramuscular or subcutaneous, skin mucosa, vein, urethra, vagina and the like.

In addition to preparing medicines, various food additives such as antioxidants, pigments, enzyme preparations and the like can be added into the notoginsenoside R1 to prepare health-care food according to the conventional method in the field.

The invention will be further illustrated with reference to the following specific examples. It should be understood that these examples are for illustrative purposes only and are not intended to limit the scope of the present invention. The experimental procedures, in which specific conditions are not noted in the following examples, are generally carried out according to conventional conditions or according to conditions recommended by the manufacturers. All percentages, ratios, proportions, or parts are by weight unless otherwise specified.

Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art. In addition, any methods and materials similar or equivalent to those described herein can be used in the methods of the present invention. The preferred embodiments and materials described herein are intended to be exemplary only.

The features mentioned above with reference to the invention, or the features mentioned with reference to the embodiments, can be combined arbitrarily. All the features disclosed in this specification may be combined in any combination and each feature disclosed in this specification may be replaced by alternative features serving the same, equivalent or similar purpose. Thus, unless expressly stated otherwise, the features disclosed are merely generic examples of equivalent or similar features.

Detailed Description

1. Experimental Material

1.1 medicinal materials

Notoginseng radix saponin R1 (CAS: 80418-24-2, molecular weight 933.13, HPLC purity not less than 98%, Shanghai Yilin Biotech Co., Ltd.)

1.2 Experimental animals

Db/db female mice weighing 50 ± 5g (twelve weeks), provided by the laboratory animals center of the university of medicine in shanghai, animal certification No.: SCXK (Jing) 2011-0012. Placing in conventional breeding environment, breeding in cages, and freely taking food and drinking water.

2. Experimental methods

2.1 diabetic Damage model establishment

After isoflurane anesthesia, the back skin was shaved off and the skin was disinfected routinely by a literature molding method (Nature Protocols,2013,8: 302-309), and circular incisions were made on both sides of the back spine, up to the fascia, using a 6mm diameter punch. To prevent the wound from shrinking automatically, silicone gaskets (0.5 mm thick, 9mm inner diameter, 18mm outer diameter) were attached to the edges, respectively, and sutured to the skin. The day of operation is counted as postoperative day 0, and so on.

2.2 methods of grouping and administering drugs

Blank control group: sterile ultrapure water (15 uL/wind)

Positive control group: vascular Endothelial Growth Factor (VEGF) (1.0mg/mL,15 uL/surround).

The medicine group is as follows: notoginsenoside R1(15mg/mL,15 uL/wind).

10 of them were administered every two days starting on the day of surgery, and the wounds were covered with a bio-permeable film after administration.

2.3 wound healing observations:

Wound pictures were taken every other day, starting on the day of surgery, at a fixed height using a digital camera and the wound area was calculated by Image J software.

2.4 statistical analysis

All experimental data were repeated 3 times, the results were expressed as mean ± standard deviation, and One-way analysis of variance (One-way ANOVA) and LSD test were performed on the experimental data using SPSS13.0 statistical software, with P <0.05 being statistically significantly different.

3. Results

3.1 Effect of notoginsenoside R1 on wound healing in db/db mice.

TABLE 1 Effect of notoginsenoside R1 on wound area in db/db mice

Fig. 1 shows the influence of notoginsenoside R1 on wound healing of db/db mice, from day 8 to day 18 after operation, the wound area of the mouse db/db with notoginsenoside R1 administration group is obviously smaller than that of the blank control group, and the two groups have significant difference (P < 0.05).

Fig. 2 shows that the wound healing of the group with notoginsenoside R1 administration and the blank group is at 0, 8, 12 and 14 days.

As can be seen in FIG. 3, the average healing days of the wounds of db/db mice in the group administered with notoginsenoside R1 was 15.2 days, which was significantly lower than that of the blank control group (21.2 days) (P < 0.001).

The research results show that the notoginsenoside R1 can effectively promote the wound healing of the diabetic mouse and obviously shorten the wound healing time.

The various aspects of the invention are addressed above. It should be understood, however, that equivalent changes and modifications may be made thereto by those skilled in the art without departing from the spirit of the present invention, and that such changes and modifications are intended to be covered by the appended claims.

Claims

1. An application of notoginsenoside R1 as the only active component in preparing the medicine for preventing diabetic foot is disclosed.

2. An application of notoginsenoside R1 as the only active component in preparing the medicines for preventing and treating diabetic gangrene is disclosed.