Composition for treating skin wounds, comprising complex herbal extract

Abstract

The present invention relates to a composition for wound treatment or skin regeneration, comprising an extract from one or more selected from the group consisting of Trichosanthes kirilowii (T. kirilowii), Pueraria lobata (P. lobata), Liriope platyphylla (L. platyphylla), Poria cocos (P. cocos), Prunus mume (P. mume), Astragalus membranaceus (A. membranaceus), Panax ginseng (P. ginseng), and Glycyrrhiza uralensis (G. uralensis). The composition has low cytotoxicity and exhibits wound-healing effects, particularly therapeutic effects on extensive skin ulcers such as diabetic skin ulcers.

Description

A composition for treating skin wounds containing a complex herbal medicine extract

[0001] The present invention relates to a composition for treating skin wounds comprising a complex herbal medicine extract, and in particular, a method for treating a wide range of skin diseases, such as diabetic skin ulcers, using said composition.

[0002]

[0003] Diabetes is a disease characterized by persistently high blood sugar levels, which can lead to various complications. Among these, skin inflammation is a common issue in diabetic patients, primarily caused by various factors such as a weakened immune system due to hyperglycemia, impaired blood circulation, and nerve damage. In particular, extensive skin ulcers in diabetic patients cause significant discomfort and can develop into infections if not treated properly, thus requiring prompt and effective treatment.

[0004]

[0005] Currently, the primary methods used to treat diabetic skin ulcers are drug treatments such as antibiotics, anti-inflammatory drugs, and topical steroids. However, these treatments can cause side effects with long-term use and may be ineffective for some patients. Therefore, there is a need for new, safer, and more effective treatment methods.

[0006] Herbal ingredients have a long history and tradition of being used to treat various diseases, and their efficacy is being proven through recent scientific research. In particular, as naturally derived substances, herbal ingredients have relatively few side effects and exhibit diverse physiological activities, making them useful for the prevention and treatment of various diseases. The potential efficacy of herbal ingredients is also attracting attention in the treatment of extensive skin wounds, such as diabetic skin ulcers.

[0007]

[0008] After conducting research on a substance that has a therapeutic effect on skin wounds, particularly skin ulcers caused by diabetes, from a herbal composition that has fewer side effects and lower toxicity than synthetic steroids, the inventors confirmed that using a combination of herbal extracts has a therapeutic effect on skin wounds or diabetic ulcers, and thus completed the present invention.

[0009] Accordingly, the objective of the present invention is to provide a wound healing composition comprising one or more extracts selected from the group consisting of Trichosanthes kirilowii, Pueraria lobata, Liriope platyphylla, Poria cocos, Prunus mume, Astragalus membranaceous, Panax ginseng, and Glycyrrhiza uralensis.

[0010] Another objective of the present invention is to provide a composition for treating diabetic skin ulcers comprising one or more extracts selected from the group consisting of Trichosanthes kirilowii, P. lobata, Ophiopogon japonicus platyphylla, P. cocos, P. mume, Astragalus membranaceus, P. ginseng, and Glycyrrhiza uralensis.

[0011] Another objective of the present invention is to provide a composition for skin regeneration comprising one or more extracts selected from the group consisting of Trichosanthes kirilowii, P. lobata, Ophiopogon japonicus platyphylla, P. cocos, P. mume, Astragalus membranaceus, P. ginseng, and Glycyrrhiza uralensis.

[0012]

[0013] To achieve the above objectives, the present invention provides a wound healing composition comprising one or more extracts selected from the group consisting of Trichosanthes kirilowii, Pseudomonas lobata, Ophiopogon japonicus platyphylla, Pseudomonas cocos, Pseudomonas mume, Astragalus membranaceus, Pseudomonas ginseng, and Glycyrrhiza uralensis.

[0014] To achieve another objective of the present invention, the present invention provides a composition for treating diabetic skin ulcers comprising one or more extracts selected from the group consisting of Trichosanthes kirilowii, Pseudomonas lobata, Ophiopogon japonicus platyphylla, Pseudomonas cocos, Pseudomonas mume, Astragalus membranaceus, Pseudomonas ginseng, and Glycyrrhiza uralensis.

[0015] To achieve another objective of the present invention, the present invention provides a skin regeneration composition comprising one or more extracts selected from the group consisting of Trichosanthes kirilowii, P. lobata, Ophiopogon japonicus platyphylla, P. cocos, P. mume, Astragalus membranaceus, P. ginseng, and Glycyrrhiza uralensis.

[0016]

[0017] The present invention will be described in detail below.

[0018] As one aspect of the present invention, the present invention relates to a wound healing composition comprising one or more extracts selected from the group consisting of Trichosanthes kirilowii, P. lobata, Ophiopogon japonicus platyphylla, P. cocos, P. mume, Astragalus membranaceus, P. ginseng, and Glycyrrhiza uralensis.

[0019] Trichosanthes kirilowii is the root of the Trichosanthes kirilowii plant. It is known to have a cold nature, be effective against coughs and phlegm, and possess fever-reducing properties. The *Compendium of Materia Medica* states that it "smooths the throat and stops diabetes," and it has excellent anti-inflammatory and antioxidant effects.

[0020] Pueraria root (*P. lobata*) refers to the dried root of the kudzu vine, a perennial plant belonging to the legume family. It is beneficial for relieving hangovers and possesses anti-inflammatory and antioxidant effects, making it effective for skin care and anti-aging. In particular, it is known to be effective for menopausal symptoms due to its action similar to female hormones. With excellent diaphoretic and antipyretic properties, it helps alleviate symptoms of colds, body aches, and pharyngitis, and is used to reduce heat in the stomach to relieve indigestion, abdominal pain, and food stagnation.

[0021] Ophiopogon japonicus (*L. platyphylla*) is a perennial plant belonging to the Liliaceae family. It is highly resistant to cold and shade, maintaining its green leaves even in the dead of winter and thriving in shade, making it widely used as an ornamental plant. It is effective in stopping coughs and clearing phlegm, so it is widely used in the treatment of lung diseases such as the common cold and asthma.

[0022] Poria cocos is a basidiomycete fungus belonging to the family Polyporaceae in the order Polyporales, and it generally grows parasitically on the roots of conifers. Poria cocos is a medicinal herb known for its diuretic, sedative, and tonic effects, and it is also known to be effective against gonorrhea, abdominal pain, and diarrhea.

[0023] Omae is a medicinal herb made by smoking and drying unripe green plums (*P. mume*). Its Latin name is *mume fructus*, and it is called *umei* in Chinese and *ubai* in Japanese. Omae has an astringent and sour taste that astringes the lungs and large intestine, effectively stopping coughs and diarrhea. It is also effective for thirst and vomiting, and is therefore used as a medicinal herb.

[0024] Astragalus membranaceus is a plant belonging to the legume family. It is a medicinal herb used in many tonics due to its near-zero toxicity, and it is known to be effective for strengthening the body, stopping sweating, promoting urination, and relieving symptoms. In other words, because it has the effect of reducing sweating, it is widely used as an ingredient in summer health foods. Astragalus is known to have many benefits, including strengthening the body, promoting blood circulation, boosting immunity, and preventing aging.

[0025] Ginseng (*P. ginseng*) is a perennial plant belonging to the Araliaceae family and is a representative medicinal crop widely cultivated in the Korean Peninsula, Manchuria, and the Primorsky Krai region. It was named "ginseng" because its root resembles a human. Ginseng possesses a wide range of benefits; in particular, it is widely used as an ingredient in health functional foods due to its effectiveness in boosting immunity, relieving fatigue, improving blood circulation, alleviating menopausal symptoms, enhancing memory, and acting as an antioxidant. Ginseng contains saponins, also known as ginsenosides, which are known to possess immune-boosting, anticancer, and antioxidant properties, as well as showing efficacy against certain degenerative diseases.

[0026] Glycyrrhiza uralensis is a perennial plant belonging to the legume family. Due to its sweet taste, it is widely used as a medicinal herb and a sweetener. While many benefits have been reported, it is a medicinal herb often prescribed alongside other herbs because it provides gastroprotective effects or mitigates the toxicity of other medicinal herbs.

[0027] The extract of the present invention is a complex extract obtained by extracting the above-mentioned herbal medicines alone or by mixing one or more of them. The herbal medicines included in the complex extract are not limited in content, but may be appropriately mixed and used in a ratio capable of exhibiting medicinal effects. For example, based on the weight of the total herbal medicines, they may be included in an amount of 10 to 20 weight% of Trichosanthes kirilowii root, 10 to 20 weight% of Pueraria root, 5 to 15 weight% of Ophiopogon japonicus, 5 to 15 weight% of Poria cocos, 5 to 15 weight% of Prunella vulgaris, 5 to 15 weight% of Astragalus membranaceus, 5 to 15 weight% of Panax ginseng, or 5 to 15 weight% of Glycyrrhiza glabra.

[0028] In addition, the solvent of the above extract is not limited to any specific type but may include one or more from the group consisting of water, organic solvents, or a mixture thereof, and the organic solvent is C 1-6 It may include one or more selected from the group consisting of lower alcohols such as methanol, ethanol, butanol, hexanol, ethyl acetate (EA), chloroform, propanol, isopropanol, 1,3-propanediol, pentanol, acetone, ether, diethyl ether, or ethyl methyl ketone, but is not limited thereto.

[0029] The above extraction may utilize extraction methods available in the industry, but is not limited thereto; methods such as heat extraction, cold maceration extraction, reflux cooling extraction, or ultrasonic extraction may be used. The above extraction may be performed at room temperature or under heated conditions and may vary depending on conditions such as the extraction solvent and extraction time.

[0030]

[0031] The present invention relates to a composition for wound healing. In this specification, the term 'wound healing' refers to a treatment process of recovering and regenerating skin from a state in which skin tissue is damaged, and may include all processes of recovering and regenerating skin tissue, such as wounds, cuts, abrasions, burns, pressure skin ulcers, or chronic skin ulcers such as diabetic skin ulcers, venous ulcers of the lower extremities, surgical wounds, etc.

[0032] In addition, the composition of the present invention may have a ‘skin regeneration’ effect along with wound healing, and the ‘skin regeneration’ may include a process of repairing skin tissue damaged by various causes such as wounds, ulcers, skin diseases, injuries, skin inflammation, or skin cutting such as surgery, or scars caused by said damage.

[0033] The composition of the present invention may be a pharmaceutical composition. In this specification, 'treatment' means any act in which symptoms are improved or benefited by the administration of the pharmaceutical composition, and may include wound healing, regeneration of damaged skin tissue, alleviation or treatment of inflammatory reactions, and the wound healing may include the treatment of diabetic skin ulcers.

[0034] The pharmaceutical composition of the present invention may be formulated into an oral or parenteral administration formulation according to conventional methods. The oral administration formulation may be a granule, powder, liquid, tablet, capsule, dry syrup, or a combination thereof. The parenteral administration formulation may be formulated as an injection or a topical application for the skin and may additionally include a carrier or excipient necessary for the formulation. Pharmaceutically acceptable carriers, excipients, and diluents that may be additionally included in the above active ingredient include lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, acacia gum, alginate, gelatin, calcium phosphate, calcium silicate, cellulose, methyl cellulose, microcrystalline cellulose, polyvinylpyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, magnesium stearate, and mineral oil. When formulating, it is prepared using diluents or excipients such as commonly used fillers, extenders, binders, wetting agents, disintegrants, and surfactants.

[0035] In particular, the composition of the present invention may be formulated as a topical skin preparation, and the topical skin preparation may be a cream, gel, ointment, skin emulsifier, skin suspension, transdermal patch, drug-containing bandage, lotion, or a combination thereof. The topical skin preparation may be appropriately combined with ingredients commonly used in topical skin preparations such as cosmetics or pharmaceuticals, for example, aqueous ingredients, oily ingredients, powder ingredients, alcohols, moisturizers, thickeners, UV absorbers, whitening agents, preservatives, antioxidants, surfactants, fragrances, colorants, various skin nutrients, or combinations thereof as needed.

[0036] The above external skin preparation may be formulated with metal chelating agents such as disodium edetate, trisodium edetate, sodium citrate, sodium polyphosphate, sodium metaphosphate, and gluconic acid; caffeine, tannin, bellapamil, licorice extract, glablidin, hot water extract of the fruit of Carinus, various herbal medicines, medicinal agents such as tocopherol acetate, glycyrrhizic acid, tranexamic acid and its derivatives or salts thereof, vitamin C, magnesium ascorbate phosphate, ascorbate glucoside, arbutin, kojic acid, glucose, fructose, trehalose, etc.

[0037] The above composition comprises, based on the total weight of the composition, 0.001 wt% to 80 wt%, for example, 0.01 wt% to 60 wt%, 0.01 wt% to 40 wt%, 0.01 wt% to 30 wt%, 0.01 wt% to 20 wt%, 0.01 wt% to 10 wt%, 0.01 wt% to 5 wt%, 0.05 wt% to 60 wt%, 0.05 wt% to 40 wt%, 0.05 wt% to 30 wt%, 0.05 wt% to 20 wt%, 0.05 wt% to 10 wt%, 0.05 wt% to 5 wt%, 0.1 wt% to 60 wt%, 0.1 wt% to 40 wt%, 0.1 wt% to 30 wt%, and 0.1 wt% to 20 wt%. It may include 0.1% to 10% by weight, or 0.1% to 5% by weight of a complex extract of herbal medicines.

[0038] As one embodiment, the composition of the present invention may be a topical skin agent having a wound healing or skin regeneration promoting effect, and the topical skin agent composition may include a cream, ointment, lotion, or hydrogel patch.

[0039] The present invention relates to a wound healing and skin regeneration composition comprising one or more extracts selected from the group consisting of Trichosanthes kirilowii, P. lobata, Ophiopogon japonicus platyphylla, P. cocos, P. mume, Astragalus membranaceus, P. ginseng, and Glycyrrhiza uralensis, wherein the herbal extracts have low cytotoxicity and excellent therapeutic effects for wound healing, particularly for extensive skin wounds such as diabetic skin ulcers.

[0040]

[0041] Figure 1 is a figure showing the results of confirming the cytotoxicity of the single medicinal extracts of the present invention.

[0042] Figure 2 is a figure showing the results of confirming the cytotoxicity of the complex extract of the present invention.

[0043] Figure 3 shows the results of confirming the wound healing effect of the single medicinal extracts of the present invention in vitro.

[0044] Figure 4 shows the results of confirming the wound healing effect of the complex extract of the present invention in vitro.

[0045] Figure 5(a,b) shows the results confirming the therapeutic effect of the complex extract of the present invention on diabetic skin ulcers.

[0046] Hereinafter, embodiments are described in detail to specifically explain the present specification. However, the embodiments according to the present specification may be modified in various different forms, and the scope of the present specification is not to be interpreted as being limited to the embodiments described below. The embodiments of the present specification are provided to more completely explain the present specification to those with average knowledge in the art.

[0047] Example 1. Preparation of extract

[0048] 1-1) Preparation of single extract of raw material

[0049] Each raw herbal medicine (standard herbal medicine distribution from the Ministry of Food and Drug Safety) was weighed, and a 50% aqueous ethanol solution 10 times the weight of the raw medicine was added, and ultrasonic extraction was performed once at 40–50°C for 3 hours. Substances were removed from the extracted extract using filter paper, concentrated under reduced pressure, and then freeze-dried to obtain each raw material extract.

[0050] 1-2) Preparation of complex extract

[0051] To prepare a complex extract, each herbal medicine was weighed according to the ratios listed in Table 1, ground into a fine powder (150 μm) according to the fineness and powdering standards of the General Pharmacopoeia, and then homogeneously mixed. An appropriate amount of the mixed powder was mixed with a 50% aqueous ethanol solution at 10 times the weight of the raw materials, and a complex extract of the raw materials was prepared in the same manner as in 1-1 above. The extract was concentrated under reduced pressure and freeze-dried to obtain 25.48 g of extract (yield 25.48%).

[0052] Scientific Name | Herbal Name | Composition Ratio Trichosanthes kirilowii (Gwalru-geun) 312.5 Pueraria lobata (Gal-geun) 312.5 Liriope platyphylla (Maekmundong) 208.3 Poria cocos (Bokryeong) 208.3 Prunus mume (Omae) 208.3 Astragalus membranaceus (Omae) 208.3 Panax ginseng (Insam) 208.3 Glycyrrhiza uralensis (Gamcho) 208.3

[0053] Experimental Example 1. Confirmation of cell viability

[0054] Each raw material extract and complex extract prepared from Example 1 above were treated to HaCaT cells, and changes in cell viability were confirmed.

[0055] 1-1) Confirmation of changes in cell viability of single-ingredient extracts

[0056] The raw material extracts obtained from Example 1-1) were each treated to HaCaT cells at a concentration of 1 to 100 μg / ml for 24 hours, and the change in cell viability was confirmed.

[0057] As a result, as shown in Figure 1, it was confirmed that most of the extracts were free of cytotoxicity, and the mixture of these single extracts was also found to be free of toxicity.

[0058]

[0059] 1-2) Confirmation of changes in cell viability of the complex extract

[0060] The complex extract obtained from Examples 1-2) above was treated to HaCaT cells at concentrations of 1 to 100 μg / ml for 24 hours, and changes in cell viability were confirmed. As a result, it was confirmed that there was no significant effect on cell viability up to treatment with the extract at a concentration of 100 μg / ml compared to the control group. (Fig. 2)

[0061]

[0062] Experimental Example 2. Confirmation of wound healing effect in vitro

[0063] 2-1) Confirmation of wound healing effect of single ingredient extract

[0064] According to the method described in Life Sciences 288:1201-1242 (2022), the raw material extracts obtained from Example 1-1) were treated to HaCaT cells to determine whether they had a wound healing effect through a wound healing assay.

[0065] For the above HaCaT cells, the positive control was treated with 10 μM of Lysophosphatidic acid (LPA) and the negative control was treated with 10 μM of 2-bromopalmitate (2BP) for 48 hours, and each extract was treated at 10, 30, and 100 μg / ml to confirm the wound healing effect.

[0066] As a result, although there were differences in degree, as shown in Fig. 3a, it was confirmed that there was a healing effect on wound tissue at all of the above concentrations in the treatment groups of each raw material extract. Figs. 3b and 3c are results of visual confirmation that the area of ​​the wound tissue decreased with treatment with the above extracts.

[0067]

[0068] 2-2) Confirmation of wound healing effects of mixtures or complex extracts

[0069] In the same manner as in 2-1 above, wound healing assays were performed on the mixture of the single extracts and the complex extracts, respectively. As a result, as shown in Figure 4, wound healing effects were confirmed in cells treated with the mixture of extracts and the complex extracts, and it was confirmed that wound healing effects were present at concentrations of 10, 30, and 100 μg / ml.

[0070]

[0071] Experimental Example 3. Confirmation of healing effect on diabetic skin ulcers

[0072] 3-1) Confirmation of the healing effect of the complex extract

[0073] Diabetes-like symptoms were induced in 8-week-old male ICR mice by injecting them with streptozotocin at a concentration of 200 mg / kg. Mice with blood glucose levels of 300 mg / dl or higher were identified and selected as having induced diabetes-like symptoms, and it was confirmed whether the extract of the present invention had wound healing and reduction effects on diabetic wounds (ulcers).

[0074] The complex extract of Examples 1-2 was applied to the above wound site for 14 days by topical application (5 mg / ml, 10 mg / ml), intraperitoneal administration (IP, 50 mg / kg, 100 mg / kg), and oral administration (OA, 50 mg / kg, 100 mg / kg), respectively, and the wound healing process was observed.

[0075] As a result, the therapeutic effect of the complex extract was confirmed, as shown in Figure 5(a,b). The wound healing effect was best in the group that applied it directly to the skin for 14 days, followed by intraperitoneal administration and oral administration.

[0076] 3-2) Confirmation of Antioxidant Activity

[0077] In Section 3-1 above, an experiment was conducted to confirm the antioxidant activity of the extract. DCF (2',7'-dichlorofluorescein), a substance that exhibits fluorescence in response to reactive oxygen species (ROS), was applied to the wound site, and the extract was administered at different concentrations to check the change in the generation of reactive oxygen species over time (3 to 24 hours).

[0078] As a result, as shown in Fig. 6, the amount of active oxygen produced in the extract treatment group of the present invention was reduced for 24 hours, and it was confirmed that the effect increased in a concentration-dependent manner up to 12 hours.

[0079]

[0080] The present invention has been described above with reference to its preferred embodiments. Those skilled in the art will understand that the present invention may be embodied in modified forms without departing from the essential characteristics of the invention. Therefore, the disclosed embodiments should be considered in an illustrative rather than a restrictive sense. The scope of the invention is defined by the claims, not by the foregoing description, and all variations within the scope of the claims should be interpreted as being included in the invention.

Claims

1. A wound healing composition comprising one or more extracts selected from the group consisting of Trichosanthes kirilowii, Pueraria lobata, Ophiopogon japonicus platyphylla, Poria cocos, Prunus mume, Astragalus membranaceus, Prunus ginseng, and Glycyrrhiza uralensis.

2. In Paragraph 1, The above extract is water, C 1-6 A composition characterized by being extracted with a lower alcohol or a mixed solvent thereof.

3. In Paragraph 1, A composition in which the above wound includes a cut, abrasion, burn, post-operative wound, pressure skin ulcer, or venous ulcer of the lower extremities.

4. The composition of claim 1, wherein the composition is formulated for oral administration including granules, powders, liquids, tablets, capsules, dry syrups, or combinations thereof, or for parenteral administration including injections or topical preparations.

5. In Paragraph 4, The above-mentioned topical preparation is a composition comprising a cream, gel, ointment, skin emulsifier, skin suspension, transdermal delivery patch, drug-containing bandage, lotion, or a combination thereof.

6. A composition for treating diabetic skin ulcers comprising one or more extracts selected from the group consisting of Trichosanthes kirilowii, Pueraria lobata, Ophiopogon japonicus platyphylla, Poria cocos, Prunus mume, Astragalus membranaceus, Prunus ginseng, and Glycyrrhiza uralensis.

7. In Paragraph 6, The above composition is a composition formulated for oral administration, comprising granules, powders, liquids, tablets, capsules, dry syrups, or combinations thereof, or for parenteral administration, comprising injections or topical preparations.

8. In Paragraph 7, The above-mentioned topical preparation is a composition comprising a cream, gel, ointment, skin emulsifier, skin suspension, transdermal delivery patch, drug-containing bandage, lotion, or a combination thereof.

9. A composition for skin regeneration comprising one or more extracts selected from the group consisting of Trichosanthes kirilowii, Pueraria lobata, Ophiopogon japonicus platyphylla, Poria cocos, Prunus mume, Astragalus membranaceus, Prunus ginseng, and Glycyrrhiza uralensis.

10. In Paragraph 9, The above skin regeneration composition is a topical skin preparation comprising a cream, gel, ointment, skin emulsifier, skin suspension, transdermal delivery patch, drug-containing bandage, lotion, or a combination thereof.

Images