CN110179776B - New application of metformin, metformin composition and preparation method and application of metformin composition - Google Patents
New application of metformin, metformin composition and preparation method and application of metformin composition Download PDFInfo
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Abstract
The invention provides a new application of metformin, a metformin composition and a preparation method and application of the composition, and belongs to the technical field of wound repair. The metformin is prepared into an external application product, has remarkable effect in promoting wound healing, particularly promoting wound healing of diabetic ulcer caused by diabetes, greatly improves the pharmaceutical effect of the metformin, and reduces the pharmaceutical risk of the metformin. The metformin composition comprises components such as aloe extract, lanolin, vitamin B6, epidermal growth factor, metformin and the like, is used for being smeared on the surface of a wound to promote the healing of the wound surface, and meanwhile, the composition can repair scars caused by the wound. The preparation method of the composition is simple in process, easy to implement and suitable for popularization and use.
Description
Technical Field
The invention belongs to the technical field of wound repair, and particularly relates to a new application of metformin, a metformin composition and a preparation method and application of the composition.
Background
Wounds are injuries to normal skin tissue caused by the action of external wound-causing factors. Under normal conditions, the wound has the ability to heal itself. However, for some chronic refractory wounds (commonly called ulcers) on the body surface, such as diabetic ulcers or pressure ulcers, the wounds cannot heal or have no healing tendency for a long time without the assistance of foreign objects. The chronic difficult-to-heal wound is a key difficulty in wound repair research due to the characteristics of complex pathogenesis, long course of disease, high treatment difficulty and the like.
Metformin plays a good role in preparing medicines for relieving diabetes, and the application of metformin in promoting wound healing is disclosed in the prior art, which shows that the metformin-containing medicines can promote wound healing of diabetic mice by oral administration, and the action mechanism of the metformin-containing medicines is probably related to the hypoglycemic effect of metformin. However, the metformin for oral administration reaches the wound surface through blood circulation, the concentration of the metformin is reduced, the promotion effect on the healing of the wound surface is limited, the pharmaceutical function of the metformin is difficult to be exerted to the maximum extent, and the harm of the metformin for oral administration to human organs is not negligible.
Disclosure of Invention
In view of this, the invention provides a new application of metformin, which can rapidly promote wound healing, has high metformin medicinal efficiency, and reduces metformin medicinal risk.
The invention also provides a metformin composition capable of effectively promoting wound healing and repairing wound injury, a preparation method of the composition and application of the composition in promoting wound healing.
The technical scheme adopted by the invention for solving the technical problem is as follows:
application of metformin in preparing externally applied product for promoting wound healing is provided.
A metformin composition comprises the following components in percentage by weight: 50-70% of aloe extract, 2-10% of epidermal growth factor, 5-10% of vitamin B6, 1-5% of lanolin, 10-40% of metformin or pharmaceutically acceptable salt of metformin, and the balance of auxiliary additives.
A process for preparing a metformin composition as described above, comprising the steps of:
a. mixing Aloe extract and lanolin, heating to 40 deg.C, and stirring thoroughly;
b. cooling the mixture of the aloe extract and the lanolin fully stirred and fused in the step a to room temperature, sequentially adding the metformin or pharmaceutically acceptable salt of the metformin and the vitamin B6, and uniformly stirring to prepare a composition precursor;
c. emulsifying the composition precursor prepared in the step b to prepare an emulsified precursor;
d. and c, cooling the emulsified precursor prepared in the step c to reduce the temperature of the emulsified precursor to 2-8 ℃, adding the epidermal growth factor and the auxiliary additive at the temperature of 2-8 ℃, and uniformly stirring.
The application of the metformin composition as an external application medicine for promoting wound healing and repairing wound left after wound healing.
By adopting the technical scheme, the invention has the beneficial effects that: the application of the metformin to preparing an external application product has obvious effects on promoting wound healing, particularly promoting wound healing of diabetic ulcer caused by diabetes, greatly improves the pharmaceutical effect of the metformin and reduces the pharmaceutical risk of the metformin. Secondly, the invention provides a metformin composition, which comprises aloe extract, lanolin, vitamin B6, epidermal growth factor, metformin and other components, and is used for being smeared on the surface of a wound to promote the healing of the wound surface. The invention also provides a preparation method of the composition, which is simple in process, easy to implement and suitable for popularization and use.
Detailed Description
The technical solution and the technical effect of the present invention are further described below with reference to the embodiments of the present invention. It should be noted that these examples are only for illustrating the present invention, and are not intended to limit the scope of the present invention.
Example 1:
first, preparation of experiment
1. Experimental animals: a plurality of SD male rats are purchased from an animal experiment center of Ningxia medical university, are 9 weeks old, have weight (180g-220g), and are randomly divided into two large groups, namely a normal group and a diabetes group, wherein the normal group and the diabetes group are respectively provided with 11 small groups which are respectively marked as a control group, metformin groups I-IV and compositions I-VI. Streptozotocin is adopted to induce the diabetes of rats in the diabetes group to generate diabetes, and a diabetes model is established.
2. Rat wound surface establishment
The skin of the back of a normal group of rats is prepared (the back rat hair is scraped by a blade), 4 full-layer skin wound surfaces are respectively prepared on two sides of the middle of the back of the rat by using a skin drill (a circular skin sampler) with the diameter of 5mm, and the distance between the wound surfaces is more than 2 cm. After the preparation of the wound surface is finished, if bleeding does not occur and the size is consistent, the preparation of the wound surface is judged to be successful.
The method comprises the steps of preparing skin of the back of a rat in a diabetic group (scraping the hair of the rat on the back with a blade), preparing 1 full-layer skin wound in the middle of the back of the rat by using a skin drill (a circular skin sampler) with the diameter of 2cm, and preparing the wound by referring to a classical chronic wound preparation method without repeated description.
3. Preparation of pharmaceutical agents
Grinding the metformin enteric-coated tablets into powder by using a mortar, adding vaseline to prepare cream, and adding proper amount of picric acid to prepare the metformin preparation with the mass concentrations of 10% (metformin I group), 20% (metformin II group), 30% (metformin III group) and 40% (metformin IV group).
Metformin compositions were prepared in the weight ratios shown in table 1.
TABLE 1 metformin composition configuration
The method of formulating the metformin composition comprises the steps of:
a. mixing Aloe extract and lanolin, heating to 40 deg.C, and stirring thoroughly;
b. b, cooling the mixture of the aloe extract and the lanolin which are fully stirred and fused in the step a to room temperature, sequentially adding metformin or pharmaceutically acceptable salt of the metformin and vitamin B6, and uniformly stirring to prepare a composition precursor;
c. emulsifying the composition precursor prepared in the step b to prepare an emulsified precursor;
d. and c, cooling the emulsified precursor prepared in the step c to reduce the temperature of the emulsified precursor to 2-8 ℃, adding the epidermal growth factor and the auxiliary additive at the temperature of 2-8 ℃, and uniformly stirring.
Wherein the auxiliary additive includes but is not limited to at least one of perfume, pigment, preservative or antioxidant.
Second, the experimental process
The metformin preparation and the metformin composition prepared in the steps are applied to the wound parts of rats of normal combination diabetes groups of corresponding groups, and a picric acid preparation is added in the preparation so as to prevent the rats from licking.
The animals were observed, photographed, measured and recorded for healing of the wounds on days 1, 3, 6, 9 and 12 of the experiment, respectively, and the rats were sacrificed at the corresponding times and skin tissue samples were collected for examination. The data content of the measurement record mainly comprises the wound size (S), the PCNA (P) of the tissue near the wound and the wound margin thickness (H).
When the material is taken, the tissue sample is trimmed to be square along the 5mm position of the periphery of the wound edge, the tissue sample is trimmed to be two halves along the maximum meridian of the wound surface, and the half is fixed for detection of immunofluorescence, immunohistochemistry, HE staining and the like of the section. And the other half is frozen at-80 ℃ for detection of WB, RCR and the like.
Third, statistics of results
Experimental results data statistics are shown in tables 2 and 3, where S is in mm and H is in μm.
TABLE 2 statistics of normal group measurements
TABLE 3 statistics of diabetes group measurements
Fourth, conclusion of experiment
According to the data of the wound surface size column in the table 2 or the table 3, under the action of metformin, the speed of wound surface healing is obviously accelerated, and the phenomenon of wound surface full healing occurs about the 9 th day, which is particularly obvious in the diabetes group, and it is not difficult to see that metformin can be used as an external application medicine to promote wound surface healing, especially to promote wound surface healing of diabetic ulcer caused by diabetes. Meanwhile, as is clear from the PCNA group data, when compared with the control group, the externally applied metformin can effectively increase the PCNA level in the tissues around the wound surface, which may be due to the fact that metformin itself has the function of increasing the PCNA level, and may also be a reason that metformin provides a good environment for PCNA proliferation by reducing the sugar level around the wound surface.
Meanwhile, by comparing the data of the sizes of the wound surfaces of the metformin composition group and the metformin composition group, it can be clearly seen that the metformin composition group has a more excellent effect of promoting the wound surface healing when being used alone compared with metformin. This may be related to the synergistic effect of lanolin, epidermal growth factor, vitamin B6 and aloe vera extract with metformin in metformin compositions, which in fact promotes epidermal metabolism and thus absorption of metformin by the epidermis, allowing full use of metformin. The epidermal growth factor, the vitamin B6 and the metformin are cooperated, so that pores can be shrunk, and epidermal damage can be repaired.
Example 2:
the experiment time in example 1 was prolonged, and the wound marks of the wounds of the experimental rats in each group were observed. The results of the experiment are shown in tables 4 and 5.
TABLE 4 statistical record of wound marks for Normal groups
TABLE 5 statistical recording of wound footprints in diabetic groups
Combining table 4 and table 5, it can be easily found that the metformin composition can promote the repair of wounds left after the healing of the wound surface, and it can be expected that the metformin composition has unexpected efficacy when applied to the repair of scars, the repair of acne marks, beauty treatment and the like.
While the invention has been described with reference to a preferred embodiment, it will be understood by those skilled in the art that various changes in form and detail may be made therein without departing from the spirit and scope of the invention.
Claims (7)
1. A metformin composition characterized by comprising the following components by weight: 50 to 70 percent of aloe extract, 2 to 10 percent of epidermal growth factor, 5 to 10 percent of vitamin B6, 1 to 5 percent of lanolin and 10 to 40 percent of metformin or pharmaceutically acceptable salt of the metformin.
2. The metformin composition according to claim 1, comprising the following components by weight: 50-60% of aloe extract, 5-10% of epidermal growth factor, 5-10% of vitamin B6, 1-5% of lanolin and 20-30% of metformin or pharmaceutically acceptable salt of metformin.
3. The metformin composition according to claim 2, consisting of the following components by weight: 60% aloe vera extract, 5% epidermal growth factor, 10% vitamin B6, 5% lanolin and 20% metformin or a pharmaceutically acceptable salt of metformin.
4. A process for preparing a metformin composition according to any one of claims 1 to 3, comprising the steps of:
a. mixing Aloe extract and lanolin, heating to 40 deg.C, and stirring thoroughly;
b. cooling the mixture of the aloe extract and the lanolin fully stirred and fused in the step a to room temperature, sequentially adding metformin or pharmaceutically acceptable salt of metformin and vitamin B6, and uniformly stirring to prepare a composition precursor;
c. emulsifying the composition precursor prepared in the step b to prepare an emulsified precursor;
d. and c, cooling the emulsified precursor prepared in the step c to reduce the temperature of the emulsified precursor to 2-8 ℃, adding the epidermal growth factor and the auxiliary additive at the temperature of 2-8 ℃, and uniformly stirring.
5. The method of preparing a metformin composition according to claim 4, wherein the components of the metformin composition further comprise an auxiliary additive comprising at least one of a fragrance, a pigment, a preservative or an antioxidant.
6. Use of a metformin composition according to any one of claims 1 to 3 in the preparation of a medicament for external application for promoting wound healing.
7. The use as claimed in claim 6 wherein the wound is a diabetic ulcer wound caused by diabetes.
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