KR20040050154A - Composition for wound healing containing extract of Japanese Elm root bark - Google Patents

Abstract

PURPOSE: Provided is a composition for wound healing containing the extract of Ulmus macrocarpa HANCE as an active ingredient. It is applied to medicaments and cosmetics. CONSTITUTION: A wound healing composition is characterized by containing, as an active ingredient, 0.001-99 wt.% of Ulmus macrocarpa HANCE extract. It is formulated into gel, ointment, cream, external application or powder.

Description

Composition for wound healing {Composition for wound healing containing extract of Japanese Elm root bark}

The present invention relates to a composition for wound healing. More specifically, the present invention relates to a wound healing composition containing an extract of root roots of the elm tree as an active ingredient.

Elm (Ulmus davidiana var. Japonica) is a deciduous broad-leaved arborescent of the dicotyledonous nettle plant Elmaceae. In spring, young leaves are used for food, and the bark is called skin, especially the root bark is called root root. There are many kinds of elm. Among them, the elm, the round elm, and the elm are ripen in September-October, while the elm, the elm, and the elm are ripe in April-May. These trees differ only in the timing of ripening and the appearance of the bark, but have the same use as leaf or medicine.

Elm has long been known to be effective for boils and swelling and has recently been reported for its anti-oxidant, nitrite-removing and antibacterial and anticancer effects on dental caries.

In the sense of agreement, elm trees are flat, tasteful, non-toxic, and soft, making urine well-perfumed, and eliminating intestinal and stomach fever, which is effective for enteritis, relieves swollen and insomnia.

Yoo et al. (2000, The Korean Journal of Oral Health) reported that elm root extract had antibacterial effect against dental caries.

Lee et al. (2000, Journal of the Korean Society of Food Science and Nutrition) reported that elm extract had antioxidant and nitrite scavenging activity.

Zhu et al. (2002, Chin Med J) reported that in the study of wound healing, cell proliferation of granulation tissues usually occurs within a week after injury, peaking on the fifth day.

Currently widely used drugs for treating skin wounds include baccitracin, gentamicin, kanamycin, tetracycline, oxytetracycline, meclocycline, polymyxin, nitropurazone, sulfadiazine, and fusidic acid. . However, there is no known composition for treating wounds prepared using the extract of Root-root skin as it is.

It is an object of the present invention to treat or alleviate a wound using natural extracts without the risk of side effects or toxicity caused by topical application of chemicals. In addition, by using the plant-derived natural extracts that are not objectionable and familiar to consumers, it can be used not only for topical pharmaceutical compositions but also for daily use throughout the whole body such as cosmetics. In addition, an object of the present invention is to provide a composition for treating wounds containing natural extracts that can be routinely administered for a long time on chronic wounds such as compression ulcers of spinal injury patients.

Figures 1a and 1b is a photograph of the state of the rat at 6 days after the administration of the root extract and physiological saline each for 3 days.

Figures 2a and 2b is a microscopic picture of the rat re-epithelialization process on day 6 after the root extract and physiological saline solution for 3 days each (× 100).

Figure 3a and Figure 3b is a microscopic photograph of the tissue state of rats on day 4 after the administration of the root extract and physiological saline each for 3 days (x 20).

Figures 4a and 4b is a microscopic photograph of the tissue state of rats on day 6 after the administration of the root extract and physiological saline each for 3 days (x 20).

In order to achieve the above object, the composition for wound treatment according to the present invention is characterized in that it contains the root extract as an active ingredient.

In the above wound healing composition, the root skin extract is characterized in that it is contained in a concentration of 0.001 to 99% by weight of the total composition.

In the above wound healing composition, the composition is characterized in that the pharmaceutical composition formulated as a gel, ointment, cream, external solution or powder.

In the above composition for treating wounds, the composition is any one of cosmetic formulations of softening longevity, nourishing longevity, nourishing cream, massage cream, essence, shampoo, rinse, body lotion, body cream, body cleanser, pack and soap. It is done.

Hereinafter, the wound treatment composition according to the present invention will be described in more detail.

In administering the drug, it can be said that it is effective to formulate it into a formulation having excellent dissolution of the effective drug to obtain better synergy. The wound treatment composition according to the present invention is prepared under conditions optimizing formulation stability by adding a carrier, ie, a base, a stabilizer, an emulsifier, and the like, a gel, an ointment, a cream, an external solution, and a powder having a high dissolution rate for the active ingredient. It may be formulated into a topical dosage form for skin application. Among them, gels and ointments were evaluated to show excellent efficacy.

As the base of the gel agent, fururonic F-127, carboxymethyl cellulose sodium, carbomer and the like are used. Especially, in case of the fururonic F-127, 10 to 25% by weight of the entire pharmaceutical composition, and 1 for the carbomer base The range of -5 weight% is suitable. The bases of the ointment are petrolatum, lanolin, polyethylene glycol, etc., and the emulsifiers are cetostearyl alcohol, hard fluid paraffin, cetomacrogol, propylene glycol, tween, span, cremophore. , Transcutol and the like are used, and paraoxybenzoic acid methyl ester, paraoxybenzoic acid propyl ester, and the like are used as preservatives.

In addition, the composition for treating wounds according to the present invention may be prepared in the form of a preparation for oral administration. In general, preparations for oral administration are formulated in the form of tablets, capsules. Meanwhile, the composition for wound treatment according to the present invention may be a nutritional composition or a food composition, in which case it may be formulated in a commonly used form. have.

In addition, moisturizers, skin protectants, preservatives and the like may be used. The composition ratio of the carrier and other additives as described above is determined according to the dissolution rate and properties of the effective drug.

The dosage of the pharmaceutical composition according to the present invention is a conventional external preparation, preferably applied in the morning and evening in an appropriate amount depending on the affected area once to several times a day.

Root-derived extract contained in the wound healing composition according to the present invention may be prepared by any of the following methods.

As a traditional extraction method, the elm root bark is simply immersed in water. The sticky jeans formed through this can be used.

On the other hand, it is also possible to use a heating extraction method, put the elm roots in the shaker and add the water so that the elm roots are submerged, and then heated for 3-4 hours at a boiling temperature of 70-80 ℃. Thereafter, the juice is left to bleed for 24 hours, and then the concentrated solution can be administered in a sterile syringe.

Alternatively, elm roots are placed in 50% ethanol and left overnight to obtain an extract, followed by centrifugation for 30 minutes, and the supernatants are collected and dried at room temperature. The dried extract is resuspended in distilled water, freeze-dried and stored at -20 ° C.

According to another method, 10g of various types of solvents were added to 10g of dried milk powder, and left at room temperature for 24 hours, and then shaken and filtered occasionally. Then, 10 times of organic solvent and water were sequentially added to the residue, followed by secondary extraction. Then, the extracts were combined and concentrated under reduced pressure at 60 ° C. to 100 ml to make a sample solution. The extraction solvent includes acetone, ethyl acetate, ether, methanol and the like.

<Example 1, Comparative Example 1>

Yu Geun-pi was used in this experiment and was purchased from Gyeongdong Market in Seoul, Korea. The elm root bark purchased was filled with a shaker and water was added to the elm root so as to be submerged, and then heated to a non-boiling temperature of 70-80 ° C. for 3-4 hours. Thereafter, the juice was left for 24 hours, and the concentrated solution was put into a sterile syringe and used for the experiment.

The root extract of Yu-geun was prepared as in Example 1, and the saline solution was compared to Comparative Example 1. With Example 1 and Comparative Example 1, a rat was used to demonstrate the effect of elm extract on wound healing using a full thickness wound model of the rat.

Eight of the four-week-old Sprague-Dawley rats were used as the experimental group (Example 1) and seven as the control group (Comparative Example 1). Detailed information of the rats used is shown in Table 1 below.

Week 4 gender cock Count 15 Weight (g) 130-150 Species Sprague-Dawley Rat

The wound was infused with 90 mg / kg of ketamine in the thigh and a 6 mm diameter full thickness wound using a punch biopsy approximately 2 cm outward from the middle of the head and buttocks under anesthesia. Made. The experimental group was administered with 1ml of elm extract of Example 1 and the control group was administered 1ml of saline solution of Comparative Example 1. Elm extract and physiological saline were administered three times a day from the day of the procedure until 3 days after the procedure. Wound size changes were measured at 3 and 6 days after the procedure and near visual photography was performed. In addition, tissue biopsies were performed on days 4, 6 and 14.

Experimental Example 1 Measurement of Wound Size Change

The present inventors measured the wound size in order to determine what effect on the wound size change as a result of administering the Example 1 and Comparative Example 1 as described above. The wound size was measured as 3.14 x maximum distance radius (mm) x minimum distance radius (mm).

Example 1 Comparative Example 1 start date 24.6 ± 4.0 20.8 ± 3.4 3rd day 19.6 ± 2.8 16.8 ± 5.8 6th day 6.1 ± 3.0 7.1 ± 3.0

As shown in the table, there was no significant difference in wound size with time between Example 1 and Comparative Example 1 (P> 0.05).

Experimental Example 2 Visual Observation

The present inventors photographed each state of the rats in which Example 1 and Comparative Example 1 were administered as described above, respectively. The results are shown in Figures 1A and 1B. Figure 1a shows the state of rats on day 6 after the administration of Example 1 for three days and Figure 1b shows the state of rats on day 6 after the administration of Comparative Example 1 for three days as well.

As can be seen in Figure 1a and Figure 1b, 6 days after the 6mm punch biopsy after the visual observation, it was determined that the color change of the epithelium in general when Example 1 was treated.

Experimental Example 3 Histological Observation I-Re-epithelialization Process

The present inventors observed the re-epithelialization process by the administration of Example 1 and Comparative Example 1. This experimental example also observed the tissue under a microscope 6 days after starting the administration of Example 1 and Comparative Example 1 as in Experiment 1 (× 100). The results are shown in Figures 2A and 2B. In the case of Fig. 2A which is the result of Example 1, re-epithelialization was observed in the arrow part, but in the case of Fig. 2B which is the result of Comparative Example 1, no re-epithelialization was observed.

Experimental Example 4: Histological Observation II-Tissue Observation over Time

The present inventors observed how the tissue changes with time by the administration of Example 1 and Comparative Example 1. First, the tissues of Example 1 and Comparative Example 1 were observed under a microscope on day 4 from the start of the administration (× 20). The results are shown in Figures 3A and 3B. There was no difference in angiogenesis, number of inflammatory cells, fibroblasts and number of macrophages between Example 1 and Comparative Example 1 on the fourth day of the experiment.

However, on the sixth day of the experiment, the tissues of Example 1 and Comparative Example 1 were observed under a microscope as described above (× 20). However, in Example 1, the growth of granulation tissue was much thicker than that of Comparative Example 1. Could be observed. The result is as shown in Figs. 4A and 4B.

As described in the background section above, Zhu et al. (2002, Chin Med J) reported that, in the study of wound healing, cell proliferation of granulation tissue occurs mainly within a week after injury, especially at the fifth day. Was reached. That is, around 5 days, most of the granulation tissue growth necessary for wound healing occurs. By the way, the granulation tissue growth state of Example 1 observed on the 6th day in the present experimental example is significantly thicker than Comparative Example 1, it can be seen that the root extract of the present invention directly affected the granulation tissue growth.

On the other hand, on the 6th day of the experiment, the degree of angiogenesis according to the administration of Example 1 and Comparative Example 1 was observed using a microscope (× 100). The results are shown in Figures 5a and 5b. However, there was no significant difference between Example 1 and Comparative Example 1 in the degree of angiogenesis (P> 0.05).

Formulation example

<Formulation Example 1: Pururon gel formulation pharmaceutical composition>

ingredient Content (% by weight) Root skin extract 5 Pururonic F-127 15 ethanol 4 Paraoxybenzoic acid methyl ester 0.10 Paraoxybenzoic acid propyl ester 0.10 pH 6.0 buffer to 100

The composition of the present invention according to Formulation Example 1 was prepared as follows. 15% by weight of Pururonic F-127 (product of BASF Co.) was added to the preparation container in a pH 6.0 buffer, followed by stirring slowly and left at 4 ° C for 20 hours to obtain a clear viscous liquid. In a separate container, 5% by weight of the root extract of the myofibril extract prepared according to the above method was added to a pH 6.0 buffer solution, dissolved by stirring, and then added to a preparation container and stirred. In another separate container, 4% by weight of ethanol, 0.1% by weight of paraoxybenzoic acid methyl ester and 0.1% by weight of paraoxybenzoic acid propyl ester were added, stirred and dissolved, and then put into a preparation container. The charged mixture was stirred for 20 minutes and then left in the refrigerator for 4 to 5 hours to obtain a pale yellow viscous liquid. The resulting viscous liquid was slowly warmed until a gel was obtained.

Formulation Example 2: Pharmaceutical Composition of Ointment Formulation

ingredient Content (% by weight) Root skin extract 5 White petrolatum 15 Cetostearyl alcohol 10 Hard Flow Paraffin 7 Seto Macrogol 1.5 Paraoxybenzoic acid methyl ester 0.12 Paraoxybenzoic acid propyl ester 0.08 Purified water to 100

The composition according to Formulation Example 2 was prepared as follows. 15 wt% of white petrolatum, 10 wt% of cetostearyl alcohol, 7 wt% of hard fluid paraffin, and 1.5 wt% of cetomacrogol were melted by heating to about 65 ° C., and the molten liquid was filtered through a 100 mesh sieve. Purified water was poured into a separate container, 5% by weight of the root extract of the roots were stirred, dissolved, and then put into a preparation container. In another separate container, dissolve 0.12% by weight of paraoxybenzoic acid methyl ester and 0.08% by weight of paraoxybenzoic acid propyl ester in purified water at 95 ° C., add it to the preparation container, stir for about 20 minutes, and then use a homogenizer. The emulsion was emulsified at a speed of 2500 rpm for 20 minutes, and then cooled slowly with stirring.

Formulation 3: Pharmaceutical Composition of Powder Formulation

ingredient Content (% by weight) Root skin extract 4 Chitosan 2 Talc 0.5 Magnesium stearate 0.5 Microcrystalline cellulose 93

All of the raw materials listed in Table 5 were placed in plastic bags and thoroughly mixed for about 20 minutes by hand. However, chitosan was previously pulverized with a small pulverizer and used only a raw material that was sifted into an 80 mesh sieve.

Formulation 4: Composition of Cream Formulation for Dry Skin

ingredient Content (% by weight) vaseline 8.0 Hydrogenated cocoglycerides 7.0 Isodecyl Neopentanoate 3.0 Simmondsia Chinensis (Jojoba) Oil 1.2 Butylene Glycol 1.5 Cetearyl alcohol 2.5 Glycerol 5.0 Squalane 4.0 Root skin extract 4.0 Laureth-23 2.2 Titanium dioxide 5.2 Non-saponified Soy Glycine (Soy) Oil 6.1 Capryl / Capric Acid Triglycerides 2.3 Phenoxyethanol 0.2 Cetearyl Glucoside 0.2 Soybean Seed Extract 5.8 Spices 0.4 Sophora Japonica 6.8 Tocopheryl acetate 0.5 Candelilla wax 0.4 CI 77891 0.1 Methylparaben 0.2 mica 0.3 Propylparaben 0.1 Ethylhexyl palmitate 0.2 Chlorphenesin 0.1 Acrylate / C10 to C30 Alkyl Acrylate Crosslinked Polymer 0.2 Xanthan Gum 0.2 Disodium EDTA 0.2

Each component of each content shown in Table 6 above was treated according to a conventional method to prepare a composition of a dry skin cream formulation.

<Formulation example 5: cosmetic composition of the milk lotion formulation>

ingredient Content (% by weight) glycerin 3.0 Butylene glycol 3.0 Propylene glycol 2.2 Carboxy Vinyl Polymer 0.2 Liquid paraffin 7.5 Squalene 3.8 Caprylic / Capric Triglycerides 4.0 Cetostearyl alcohol 1.6 Stearic acid 0.8 Polysorbate 60 1.5 Sorbitan monosulfate 0.7 Triethanolamine 0.31 antiseptic Quantity Root skin extract 5.0 Spices Quantity Pigment Quantity Purified water to 100

Each component of each of the above contents was mixed according to a conventional method to prepare a cosmetic composition of a milk lotion formulation.

By using the composition for wound healing according to the present invention, it is possible to treat or alleviate a wound using a natural extract without the risk of side effects or toxicity caused by topical application of chemicals, and there is no objection to the consumer and a familiar vegetable. The natural extract can be used to provide not only topical pharmaceutical compositions, but also compositions that can be used for daily use throughout the body, such as cosmetics. In addition, there is an advantage that can be administered routinely for a long time for chronic wounds such as compression ulcer of spinal injury patients.

Claims (4)

A composition for treating wounds, which contains the extract of Root-root skin as an active ingredient. The method of claim 1, wherein the extract of the roots of the root composition for wound treatment, characterized in that contained in a concentration of 0.001 to 99% by weight of the total composition. The composition of claim 1, wherein the composition is a pharmaceutical composition formulated as a gel, ointment, cream, external solution or powder. According to claim 1 or claim 2, wherein the composition is a soft cosmetics, nourishing cosmetics, nourishing cream, massage cream, essence, shampoo, rinse, body lotion, body cream, body cleanser, pack and soap any one cosmetic formulation Wound treatment composition characterized in that.