WO2018012772A1 - Wound treatment composition containing uldavioside a compound - Google Patents

Abstract

The present invention relates to a wound treatment composition containing as an active ingredient an uldavioside A compound separated from an Ulmus davidiana Planch. extract. The uldavioside A compound shows excellent efficacy for wound treatment and thus can be utilized as a therapeutic agent for treating wounds.

Description

 Specification

 Name of the Invention: Composition for the treatment of wounds containing Uldabioside A compound

 Technical Field

 [1] The present invention is derived from the extract of E. coli // «'davidiana Planch)

It relates to a composition for the treatment of wounds containing the active ingredient A (Uldavioside A).

 Background

 [2] Wounds are damage to skin tissue that protects the body from external invaders and maintains moisture and body temperature. Wound healing is an essential response to normalize the function and morphology of the damaged tissue. If the wound is not treated properly, it can cause fatal damage to the internal organs, such as bacterial infections, so it is important to take action to restore the damaged skin as soon as possible and to resemble the original skin structure.

 [3] stage 1 of wound healing hemostasis and inflammation

 It consists of two stages of proliferation and three stages of remodeling, each of which is repeated and successively progressed (Bello YM, et al., 2000; Midwood KS, et al., 2004; Stadelmann WK, et al., 1998).

 [4] When wounds occur, the first stage of cognitive hematopoietic and inflammatory reactions occurs, in which hemostasis aggregates into areas of platelet abnormality, forming a fibrin clot, preventing bleeding (Midwood KS, et. al., 2004; Sandeman SR, et al., 2000). Inflammatory reaction is caused by phagocytosis of bacteria or tissue debris.

 As it is removed, several cytokines are released from the macrophage and migrate into cells that differentiate into the growth.

 Mitosis is increased.

 [5] In the second stage of authentication, neovascularization, collagen accumulation, granulation tissue formation, epithelialization, and wound shrinkage occur (Midwood KS, et al., 2004; Chang HY, et al., 2004). This is the initial stage for wound fusion and re-arrangement of collagenous fibers, which result in the appearance of fibroblasts in the wound (Byl NN, et al., 1992).

 [6] Finally, during maturation, the wound space is completely replaced by granulation tissue, blood vessel formation is maximized, and the amount of collagen fibers is enriched, and the epithelial cell recovers its normal thickness (Galeano M., et. al, 2008; Garg HG, et al., 2000).

[7] Step-by-step treatment of wound healing If the debris of tissues, foreign bodies, and necrotic tissues is not removed by inflammatory cells, the next step is to treat the next stage of authentication. The role of salt phase is very important because the process is delayed (Enoch P., et al., 2004).

[8] A closer look at the reactions that occur to the inflammatory phase,

 Contraction in the virtual site of histamine, bradykinin, prostaglandin, serotonin,

Blood vessels are enlarged by the release of norepinephrine, which is caused by the expansion of blood vessels, which leads to the formation of oils between endothelial cells, which can cause plasma and leukocytes to escape into the interstitial fluid. Polymorphonuclear leukocytes, which are affected by the complement, move to the wound, where they feed on damaged tissue debris and bacteria, and several hours after the wound is created, the macrophages reach the damaged site for phagocytosis. Activated macrophages generate several cytokines and reactive oxygen species (ROS) to activate NF-KB (nuclear factor-κΒ), a transcription factor for inflammatory reactions, resulting in iNOS (inducible nitric oxide ^: synthase)

Inflammation is triggered by increasing the expression and activity of cyclooxygenase-2 (COX-2) to produce excess NO (nkric oxide) and PGE ₂ (prostaglandin E2).

 Free radical species generated from macrophages remove the bacterium from the wound to prevent infection and act as a secondary messenger in the cell, playing an essential role in the wound healing phase. It is known to slow down the wound healing rate by inducing oxidative stress on the site and regulating the expression of inflammatory reaction mediators, thereby affecting the inflammation response and thus inhibiting the formation of excessive reactive oxygen species. An attempt is being made to find (Park Eun-kyo, 2011).

[9] The JJlmus davidiana Planch is a locust tree belonging to the ulaceae family.

C // davidiana var. ^ pcra ^' ra Nakai) is a dried bark and root bark of the cork.The herbal root is sweet, nontoxic, used for swelling, arthritis, gastric ulcers, gastrointestinal diseases, and has excellent effects on expectorants, anticancer, wound healing drugs, and inflammation. (Duke JA, 1985), a natural substance present in pectoralisemia.

 β-cytosterol, phytosterol, stimasterol, tannin, starch, polysaccharide, etc.

 Medelin and the components that indicate analgesic activity

 Separation of epipreendera (epifriendelalol), taraxerol (taraxerol), etc. (Matsuzaki T., et al '1985) and chemical composition studies (Duke JA, 1985), but the various physiological activities of root skin Attempts to study have not been made yet.

 [10] The present inventors were able to complete the present invention in the course of studying the wound healing composition containing the extract of root skin, by confirming that the treatment effect of Uldabioside A compound isolated from the root skin extract was superior.

[11] As a prior art, Korean Laid-Open Patent Publication No. 2000-0041190 includes milky skin The prevention and treatment of diseases such as inflammation and wounds of pharmaceutical compositions are described. Korean Patent Laid-Open Publication No. 2004-0050154 describes a wound healing composition containing a root skin extract, but it is described as Uldabioside A compound. There is a difference in the composition of the present invention: Korean Patent No. 0893166 describes the proliferation and antioxidant effects of the fibroblasts of the locust tree extract, but the Uldabioside A compound and the wound treatment have not been mentioned. There is a difference with the configuration.

[12] In addition, as a non-patent document, Son B.W., et al. Describe a dabioside A compound isolated from a locust tree, but no wound healing effect has been described.

 Detailed description of the invention

 Technical task

 [13] The purpose of the present invention is to isolate from mi davidiana Planch extract.

 An object of the present invention is to provide a composition for treating a wound, comprising an active ingredient of Uldavioside A.

 Task solution

 [14] The present invention provides a compound of Ulvidioside A of Formula 1

 It relates to the composition for the treatment of wounds as an active ingredient.

[15] [Formula 1]

[17] The wounds include wounds, bedsores, burns, abrasions, punctures, ulcer wounds, wounds, free radicals, chronic skin wounds, bruises, cuts, throat or oral mucosa wounds, lacerations, diabetic ulcers, lower extremity ulcers, It can be selected from the group consisting of hypertensive ischemic ulcers, venous ulcers, and foot ulcers.

 [18] The composition is based on the total increase in composition of the Uldabioside A compound.

 It may be contained in 0.001 to 50% by weight.

The composition may be a pharmaceutical preparation formulated as an oral administration agent, a spraying agent, a gel, an ointment, a cream, or an external preparation.

[20] Hereinafter, the present invention will be described in detail.

 [21] The present invention relates to a composition for wound healing, which contains the compound of the following formula (1) as Davioside A.

[22] [Formula 1]

The Uldabioside A compound of Chemical Formula 1 may be synthesized according to a conventional method, may be prepared as a pharmaceutically acceptable salt, or may be separated and purified from the dermis extract.

 [25] The root bark is a dried bark and root bark of the bark of the bark (t / Z / davidiana var. Japonica Nakai) belonging to the ulaceae family.

 [26] The root skin extract may be rooted in water, lower alcohols of C 1 to C 4 or their

 The mixed solution may be extracted as a solvent. The C1 to C4 alcohols may be selected from the group consisting of methanol, propanol, isopropanol, butanol and isobutanol, preferably with water.

 The compound separated from the root skin extract may be purified using column chromatography. The chromatography may include silica gel column chromatography and HP-20 column chromatography.

chromatography), RP-18 ¾ ¾ chromatography _. (RP-18 column chromatography), LH-20 column chromatography, and high-performance liquid chromatography.

 [28] The composition for treating wounds is for treating wounds with damaged skin tissue. The wounds include wounds, bedsores, burns, abrasions, punctures, ulcer wounds, cuts, and chronic skin wounds and bruises caused by free radicals. It may be selected from the group consisting of cuts, throat or oral mucosa and wounds, lacerations, diabetic ulcers, lower extremity ulcers, hypertensive ischemic ulcers, venous ulcers and foot ulcers.

 [29] The diabetic ulcer may be a diabetic foot ulcer

 The composition provides a pharmaceutical composition comprising the Uldabioside A compound and the excipient of Formula 1. The Uldabioside A compound is 0.001-50% by weight based on the total weight of the composition, preferably 0.001-40 Weight%, more preferably

 It may be contained at 0.001 to 30% by weight.

[31] The pharmaceutical composition may be in the form of oral formulations, external preparations, suppositories, and sterile injectable solutions, such as powders, granules, tablets, capsules, suspensions, emulsions, syrups, aerosols, sprays, etc., in accordance with conventional methods. Can be used in the pharmaceutical composition. Carriers, excipients and diluents that may be included include lactose, dextrose, sucrose, sorbitol, manny, xili, erysri, malty, starch, acacia rubber,

 Alginate, gelatin, calcium phosphate, calcium silicate, cellulose, methyl

 Cellulose, microcrystalline cellulose, polyvinylpyridone, water, methyl hydroxybenzoate, propyl hydroxybenzoate, talc, magnesium stearate and mineral oil. It is formulated with diluents or excipients, such as thickeners, bulking agents, binders, wetting agents, disintegrants, surfactants, and the like. Tablets for oral administration include tablets, pills, powders, granules, capsules, and the like. The at least one excipient, for example, starch, in the Uldabioside A compound of the present invention is prepared by mixing it with calcium carbonate, sucrose or lactose, gelatin and the like. In addition to simple excipients, lubricants such as magnesium stearate and talc are also used. Liquid oral agents for oral use include suspensions, solvents, emulsions, and syrups. For example, wetting agents, sweeteners, fragrances, and preservatives may be included. For parenteral administration, sterile aqueous solutions, non-aqueous solvents, suspensions, emulsions, freeze-drying agents, suppositories. Propylene glycols; vegetable oils such as recalls, polyethylene glycols, olive oil, and injectable esters such as ethyl oleate; can be used as bases for suppositories, witepsol, macrogol,

 Tween-61, cacao butter, laurin, glycerogelatin and the like can be used.

The wound therapeutic composition may be a pharmaceutical composition formulated as an oral dosage form, a spray, a gel, an ointment, a cream, or an external preparation, but is not limited thereto.

 [33] The dose of the pharmaceutical composition of the invention will depend on the age, sex, and weight of the subject to be treated, the severity of the particular disease or pathology to be treated, the severity of the disease or pathology, the route of administration and the prescriber's judgment. Dose based dose determination is within the level of skill in the art and generally dosages range from 0.01 rag / kg / day

 In the range of 2000 mg / kg / day. A preferred dosage is; lmg / kg / day to 500 mg / kg / day. Dosing can be administered once a day or hydration or divided. The above dosages are not intended to limit the scope of the present invention in any way.

 [34] The pharmaceutical composition of the present invention is used in rats, livestock, humans, and mammals:

 All modes of administration can be anticipated, e.g., by oral, rectal or intravenous, muscular: subcutaneous, endometrial or cerebral vascular injections and skin application. Because of its low toxicity and side effects, it can be used safely for long-term use for prevention purposes.

 Effects of the Invention

[35] The present invention relates to a composition for treating a wound containing an active ingredient Uldabioside A isolated from Ulm davidiana Planch extract, which is effective in treating an abnormality of the Uldabioside A compound. It was confirmed that there is. [36] Through this, davioside A compound of the present invention is wound, bedsores, burns, abrasions, puncture ulcer wounds, wounds, chronic skin wounds caused by free radicals, bruises, cuts, throat or oral mucosa, It is expected to be easily used as a treatment for wounds such as laceration and diabetic ulcer, lower extremity ulcer, hypertensive ischemic ulcer, venous ulcer and foot ulcer.

 Brief description of the drawings

 FIG. 1 is a cross-sectional view of an Ulviobioside A compound of the present invention.

Is an illustration showing a COSY (bold lines) and HMBC correlation between C ¾- ¹³ (arrow).

2 shows C2C12 (A) and NIH3T3 (B) of davioside A compound of the present invention.

Cytotoxicity in cells is shown. ^: ：

3 shows the effect of wound healing on C2C12 (A, B) and NIH3T3 (C, D) cells on the inflammatory stress of davioside A compound of the present invention.

4 shows the glycosylation stress of davioside A compound of the present invention.

 C2C12 (A, B) and: It shows the effect of wound healing on NIH3T3 (C, D) cells. .

[41] Figure 5 shows the effect of wound treatment in an animal model of the Uldabioside A compound of the present invention. (A) shows the wound image according to the treatment time of Ulda bioseed A compound, and (B) shows the quantified graph of the wound site.

FIG. 6 shows the results of histological changes following wound treatment in an animal model of the Uldabioside A compound of the present invention. (A) shows the results of H & E staining and (B) shows the results of trichrome staining.

7 shows the expression level of angiogenesis-related proteins VEGF and CD31 (A) and tissue regeneration-related proteins bFGF and β-catenin (B) according to wound treatment in an animal model of the Uldabioside A compound of the present invention. It shows the result of confirmation.

8 shows the glycosylation of the Uldabioside A compound of the present invention in a high sugar environment.

 It has been shown to protect HDF (A) and C2C12 (B) cells against stress.

FIG. 9 shows the present invention in a diabetic-induced animal model of dabioside A compound.

 The results of quantifying the size of the wound site (A) and the wound site (B) according to the round cut treatment are shown.

 Best Mode for Carrying Out the Invention

The preferred embodiments of the present invention will be described in detail below. However, the present invention is not limited to the embodiments described herein but may be embodied in other forms. Rather, it is here: The information presented is thorough and complete, and is provided to the person skilled in the art to fully convey the ideas of the present invention. ^:

Example 1 Separation of Uldabioside A Compound

 [48] The roots of m davidiana Planch were: purchased from a farm and dried. After adding purified water to 10g of dried rooted skin, use a semi-continuous low temperature vacuum extractor.

The extract of root skin was extracted three times at 12 ° C. for 12 hours. The filter paper was used to remove impurity to obtain the dermal hot water extract. The dermal hot water extract was obtained in 30% methanol, 50% methanol, 70% methane, and 100% methanol in the order of isocratic elution. 20 columns

Chromatography (Diaion HP-20 column chromatography) afforded three fractions (Fr. E-1-E-3). Double Fr. Uldabioside A compound (9 mg) was isolated by performing Sephadex LH-20 column chromatography according to isocratic elution conditions using E-1 as a 70% methanol isocratic solvent.

 Example 2 Physical and Chemical Structure Identification of Uldabioside A Compound

 Uldavioside A;

 Light brown powder;

NMR and ^{l 3} C NMR data see Table 1 below;

ESI-MS [M + H] ⁺ m / z 423.1, C ₂₀ H ₂₂ O ₁₀ .

TABLE 1

^! C NMR (150 MHz in C1 0D) spectroscopy data '

Ή NiVIR (600 MHz in CD ₃ OD) spectroscopy data <Experimental Example 1 Culture of Animal Cells>

 Animal cells were cultured to confirm the activity of the Uldabioside A compound of the present invention, wherein the animal cells were C2C12 cells, which are myoblasts, and

NIH3T3 and HDF (human diploid fibroblast) cells in fibroblasts Each cell contained Dulbecco's Modified Eagle's Medium (DMEM) containing 10% fetal bovine serum (FBS), 100 U / m of penicillin, and 100 zg / m of streptomycin. Incubated in 37 ° C, 5% C0 ₂ incubator.

Experimental Example 2 Confirmation of Cytotoxicity of Uldabioside A Compound

[58] Cytotoxicity by Uldabioside A Compound of the Invention

 MTT (3- (4,5-dimethylthiazol-2-yl) -2,5-diphenyltetrazolium bromide) assay method was used.

[59] C2C12 and NIH3T3 cells cultured in Experimental Example 1 were dispensed in 48 well plates at ⁵ lxlO cells per well, and cultured for 24 hours, followed by 0.5% FBS, penicillin of IOOU / I, and 100 g / streptoto. DMEM medium containing mycin was added and cultured for 18 hours. After 18 hours of culture, the Uldabioside A compound was treated with ΙμΜ and ΙΟμΜ and incubated for 24 hours, at which time C2C12 and ΝΙΗ3Τ3 cells that had not been treated were used as controls. In cells after 24 hours.

After treatment with MTT solution at a concentration of 10 g / i and reaction for 3 hours at 37 ⁰ C, the culture medium was removed, and the formed formazan precipitate was dissolved in dimethyl sulfoxide (DMSO) and absorbance was measured at 570 nm. Is also shown in Figure 2.

 [60] In Fig. 2, as shown, C2C12 (2A) treated with adavioside A compound and

 Survival rate of NIH3T3 (2B) cells compared to control group that did not process anything

 Increased.

 [61] This suggests that Daviside A compound of the present invention does not exhibit cell: toxicity.

 Experimental Example 3 Confirming the Wound Treatment Effect of Uldabioside A Compound

 [63] A wound healing assay was performed to confirm the wound healing effect of the treatment of Uldabioside A compound of the present invention.

[64] Experimental Example 3-1. Confirmation of wound treatment effect by inflammatory stress

[65] C2C12 and NIH3T3 cells cultured in Experimental Example 1 were dispensed to stabilize> 1 < 10 ^& dog cells per 12-well plate, cultured for 24 hours, stabilized, 0.5% FBS, 100 U / m penicillin and DMEM medium containing 100 / ig / of streptomycin was added and incubated for 18 hours. After 18 hours of incubation, a scratch of about 0.9 mm was placed in the center of the well in which the cells were growing and pre-reacted for 1 hour with 10 μM of Uldabioside A compound. After 1 hour, cells were treated and cultured with lO / g / mg LPS (lipoIysaccharide) for inflammatory stress stimulation. Cells were fixed at 2, 12 and 24 hours (2%).

 formaldehyde and 0.2% gkitaraldehyde), 0.3% crystal

After staining with crystal violet, the movement of cells was confirmed using a microscope, and the area reduction according to the movement of cells to the wounded area was analyzed and the results are shown in Fig. 3. Without pre-reacting Compound A, Inflammatory stress stimulation with LPS was used as a control.

As shown in FIG. 3, in the case of treating Ulda bioseed A compound of the present invention

 Cell migration against inflammatory stress was increased in both C2C12 (3A, 3B) and NIH3T3 (3C, 3D) cells compared to the control group, especially NIH3T3 cell migration activity was higher.

 Experimental Example 3-2. Confirmation of wound treatment effect due to glycated oxidative stress

[68] Diabetes is the most common complication of oxidative stress due to the breakdown of sugar in the blood. In the process of glucose breakdown, glucose oxidase produces hydrogen peroxide (H ₂ 0 ₂ ). Induces glycooxidative stress. Therefore, the effect of wound healing by glycooxidative stress of the Uldabioside A compound of the present invention was confirmed.

The experiment was conducted in the same manner as Experimental Example 3-1, and treated with 7mU / m £ glucose oxidase instead of LPS to give glycated oxidative stress stimulation, and the results are shown in FIG. 4.

[70] As shown in FIG. 4, when the present invention is treated with Ulda bioseed A compound,

 The tax on glycolytic stress compared to the control group: Pomigration was reduced to C2C12 (4A, 4B) and

 All were increased in NIH3T3 (4C, 4D) cells, especially NIH3T3 cell migration activity was higher. ：

[71] Based on the results of FIGS. 3 and 4 above, the present invention is directed to the bioseed A compound.

 The treatment effect of the wound by stress and glycation stress was excellent.

 Experimental Example 4 Confirmation of Wound Treatment Effect of Ulda Bioside A Compound

[73] Experimental Example 4-1. Confirmation of wound treatment effect through visual observation

 [74] To determine the effect of wound treatment by the Uldabioside A compound of the present invention

 Animal experiments were conducted.

[75] The hind limbs of 7-8 week old Sprague-Dawley rats were epilated, 70% alcoholized, and a 3 cm diameter flap wound was created. After the flap was randomly assigned, randomly assigned Uldavioside A compound of the present invention. The treatment group was treated with untreated ointment containing 0.025 weight ^< ¾ of Adavioside A compound (Example 1-2 below) and wounded with sterilized paper. The wound was fixed using bandages and bandages to wrap and maintain a wet environment, and the control treated ointments that did not contain AbDioside A compound. First, the wound was observed, the size of the wound was quantified, and the result is shown in FIG.

 [76] In the wound image (5A) and the graph (5B) quantified the wound region of FIG.

As shown, in contrast to the control: Wound treatment with the Uldabioside A compound showed a wound recovery from day 7, and the wound was almost treated on day 14. [77] This suggests that the Daviside A compound of the present invention has an excellent wound healing effect.

[78] Experimental Example 4-2. Histological Change Observation of Wound Therapy

[79] To determine the effect of wound treatment by the Uldabioside A compound of the present invention _: Histological changes were observed using tissues from wound-induced animals.

 After observing the wound treatment effect in Experimental Example 4-1, the rats were sacrificed to biopsy the muscle tissue of the wound and collected the tissue. 10% of the collected tissue

 Formalin was fixed for 24 hours and fixed tissues were fixed.

 Tissue sections were made by embedding paraffin and sectioning to 5β thickness. The tissue sections were deparaffinized, washed with water, washed with water, subjected to hematoxylin & eosin stain or Masson's trichrome stain and analyzed for histological changes related to wound recovery using an optical microscope: The results are shown in FIG.

 FIG. 81: H & E staining results of 6 (A): As shown, in the group administered with dada bioseed A compound, immune cells and influx decreased on the 3rd day of wound induction, and from the 7th day, neovascularization and granulation tissue were observed. Formation is active and from day 10

 Fibroblast proliferation was active, whereas the control group was wound

On the third day, the influx of immune cells was higher than that of the Adavioside A compound treatment group.

It continued until day 7. Granulation tissue formation was seen on day 10, and fibroblast proliferation was not observed.

 [81] In the case of tricrum staining, it is to identify collagen in tissues. The formation of collagen means that the wound in the dermis is restored and the function of skin tissue is restored.

 [83] Fig. 6 shows the Uldabioside A compound as shown in the tricreme staining result of 6 (B).

Nowhere else in the administration, the amount of collagen staining in 7 primary wound-induced, compared to the control ^group: We observed significant increase of 14 primary has been confirmed that the collagen is produced in many tissues.

 [84] This suggests that the Uldabioside A compound of the present invention is effective in treating wounds by wounds.

Experimental Example 4-3. Identification of changes in proteins related to angiogenesis and tissue regeneration following wound treatment

[86] To determine the effect of wound healing by dabioside A compound of the present invention: We observed changes in the expression of proteins related to vascular life and tissue regeneration during wound healing.

[87] The tissue fragments prepared on Day 10 prepared in Experimental Example 4-2 were treated with de-guapine, a function,

 After washing with water, we used antibodies of vascular endothelial growth factor (VEGF) and CD31, basic fibroblast growth factor (BFGF) and β-catenin (β-catenin), which are proteins related to angiogenesis.

Immunohistochemistry (IHC) was performed, and the expression of each protein was analyzed and the results are shown in FIG. . As shown in the results of immunohistochemical staining of FIG. 7, in the group to which the compound was administered, VEGF and CD31 (7A) related to angiogenesis, and bFGF and β-catenin, related to tissue regeneration, 7B) expression was increased compared to the control.

 [89] This suggests that the present invention and the Waldobioside A compound aberrations: excellent wound healing effects by promoting angiogenesis and tissue regeneration during treatment.

 Experimental Example 5 Diagnosis of Diabetic Disease Ulcer Treatment of Uldabioside A Compound

Experimental Example 5-1. Confirmation of Cytoprotective Activity against Glycolytic Stress of Uldabioside A Compound

 [92] The cell protective activity against the glycooxidative stress of the Uldabioside A compound of the present invention was confirmed.

[93] After incubating the C2C12 and HDF cells cultured in Experimental Example 1 each with ⁵ cells of lxlO per well on a 48 well plate for 24 hours, 50mM of

 D-glucose is used to treat high glucose conditions.

Subsequently, the Uldabioside A compound was treated with ΙΟμΜ and 20μΜ, and after 1 hour was incubated for 24 hours with 7mU / n ^ glue: cos oxidase. At this time, C2C12 or HDF cells that were not treated with anything were used as the control group 1, cells in the high sugar state control group 2 and cells treated with glucose oxidase in the high sugar state control group 3 were used. After 24 hours, each cell was treated with MTT solution at a concentration of 100 g / i and reacted for 3 hours at 37 ° C. Culture ^{: The} solution was removed, the formed formazan precipitate was dissolved in DMSO 200 and the absorbance was measured at 570 nm. The results are shown in Figure 8.

 [94] Figure: Glycosylation by Glucose Oxidase in High-sugar Environment, as shown in Figure 8

 While HDF (8A) and C2C12 (8B) cells both reduced cell viability due to stress (Control 3), the treatment of Daviside A compound of the present invention suppressed the decrease in cell viability due to glycation stress. Confirmed that:

 [95] Through this, uldabioside A compound was glycosylated in the environment of high sugar level.

 It has been found that there is a protective effect of the cells against stress, which can predict the effective treatment of wounds by the Daviside A compound of the present invention in diabetic patients with slow wound healing.

 Experimental Example 5-2. Confirmation of the treatment effect of the diabetic ulcer of the Uldabioside A compound

 [97] Animal experiments were conducted to confirm the treatment of diabetic ulcer by the Uldabioside A compound of the present invention. ：

 [98] Seven-week-old males weighing 300 g are male Sprague-Dawley rats.

Diabetes was induced by intraperitoneal injection of streptozotocin (60 mg / kg) of streptozotocin. 3 days later, venous blood was collected from the tail vein. Blood glucose was measured and only rats with a blood sugar level of 300 mg / d £ or more were selected. After removing the back part of the selected rat, the back part, which is about 4 to 5 cm away from the ear, was punched to obtain a diameter of 1 cm or 1.5 cm. After making the round cut, the rats were randomly assigned and treated with no treatment of the Uldabioside A compound of the present invention: the control group and the treatment group were divided into the control group.

 The ointment containing 0.025% by weight of Uldabioside A compound (Example 1-2 below) was treated and sterilized: the wound was fixed using bands and bandages to cover the wound with cold and maintain a wet environment. The ointment containing no dabioside A compound was treated. Thereafter, the wound was observed for 8 days at intervals of 2 days after the incidence of circular resection, and the size of the wound was quantified, and the result is shown in FIG. It was.

 [99] As shown in the round wound image (9A) and the quantified wound size (9B) in the diabetic-induced animal model of FIG. 9, the group treated with Uldabioside A compound as compared to the control group was 4 days. As the wound was recovered, the size of the wound was significantly reduced.

 [100] This suggests that the Uldabioside A compound of the present invention has a therapeutic effect on diabetic ulcer, a complication of diabetes.

 [101] <Preparation Example 1. Pharmaceutical preparation>

 [102] Formulation Example 1 Gel Preparation Pharmaceutical Formulation

 [103] After 15 weight <¾ of Pluronic F-127 (product of BASF Co.) was added to the pH 6.0 buffer solution, the mixture was stirred slowly and left at 4 ° C for 20 hours to obtain a clear viscous liquid. Uldabioside A compound of the present invention in a pH 6.0 complete solution in a separate container

Add 0.0025 weight ^< ¾, stir to dissolve, add to stirring preparation container and stir. Another weight of ethanol in 4 separate containers

 0.1% by weight of paraoxybenzoic acid methyl ester and 0.1% by weight of paraoxybenzoic acid propyl ester were added, stirred and dissolved. The mixture was added to a preparation container. The injected mixture was stirred for 20 minutes and then left in a refrigerator for 4 to 5 hours. This gave a slightly yellow viscous liquid. The gel was slowly heated until a gel was obtained from the viscous liquid obtained.

Formulation Example 1-2 Ointment Pharmaceutical Formulations

[105] White petrolatum 15 weight ^« ¾, cetostearyl alcohol 10 weight%,

7% by weight of hard fluid paraffin and 1.5% by weight of cetomacrogol were heated to about 65 ⁰ C and melted. The molten liquid was filtered with 100 mesh sieve. Poured purified water into a separate container and 0.025 weight of Uldabioside A compound of the present invention. The mixture was stirred, dissolved, and added to a preparation container. In another separate container, 0.12% by weight of methyl paraoxybenzoate and propyl ester of paraoxybenzoic acid in a boiling water of 95 ° C.

Dissolve 0.08% by weight in the preparation container, and then stir for about 20 minutes, and then emulsify with a homogenizer at a speed of 2500 rpm for about 20 minutes. Cool slowly with stirring.

 Formulation Example 1-3 Preparation of Tablet

 200 g of the dabioside A compound of the present invention was mixed with 175.9 g of lactose, 180 g of potato starch, and 32 g of colloidal silicic acid. After adding 10% gelatin solution to the mixture, the mixture was pulverized and passed through 14 mesh bodies. This was dried and the resulting mixture was purified by adding 160 g of potato starch, 50 g of active and 5 g of magnesium stearate.

Claims

Claims [1] A composition for treating wounds, characterized in that it contains an uldavioside A compound of formula 1 as an active ingredient.  [Formula 1]

[Claim 2] In paragraph 1,  Wounds, bedsores, burns, abrasions, punctures, ulcerative wounds, wounds, chronic skin wounds caused by free radicals, bruises, cuts, throat or oral mucosa wounds, lacerations, diabetic ulcers, lower extremity ulcers, hypertensive ischemic ulcers. A wound healing composition characterized by being selected from the group consisting of venous and foot ulcers.  [Claim 3] In paragraph 1,  The composition is a wound treatment composition, characterized in that the Ulda bioseed A compound is contained in 0.001 to 50% by weight relative to the total weight of the composition. [4] The method of any of paragraphs 1 to 3,  The composition is a composition for the treatment of wounds, characterized in that oral administration, spray, gel, ointment, cream, or a pharmaceutical composition formulated as an external preparation.