KR20180025789A - Composition comprising extract of quamoclit angulata for wound healing - Google Patents

Abstract

According to an embodiment of the present invention, provided is a composition for healing wounds containing a Quamoclit angulata Bojer extract of as an active ingredient.

Description

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a composition for wound healing, which contains an extract of Curcuma pseudo-acacia var.

The present invention relates to a composition for healing wounds containing an extract of Curcuma pseudo-acacia var.

Skin is the largest organ of the body and is the interface between our environment and our internal biology. The skin consists of two major layers of the epidermis, the outermost layer of the skin, and the dermis, just below the epidermis. Keratinocyte is the main cell of the skin and constitutes 95% of the epidermis.

Early keratinocytes are differentiated into chemically and physically resistant stratum corneum surrounded by proteins and lipids, including ceramides, cholesterol and fatty acids. The natural or forced removal of the top layer of the keratinized epithelium can stimulate a turnover by the underlying cells to replace damaged or lost cells.

The keratinized layer provides a protective and water-barrier function between the body and the environment. The main function of keratinocytes is to protect the body against chemical, physical and mechanical hazards, microbial invasion, heat, UV radiation and water loss (Proksch et al., 2008). Keratinocytes are also a major component of the epidermis and continuous mucosal tissue (Presland and Dale, 2000).

The wound can be defined as the collapse of the integrity of the skin epithelium. The normal wound healing process takes three steps: inflammation reaction, granulation tissue formation, neovascularization and neovascularization, and complete healing is possible when these mechanisms are properly performed. However, wound repair recovery may be delayed if wound repair process is developed abnormally. In particular, diabetic patients have a disability in the mechanism and blood vessel formation or granulation tissue formation is remarkably slower than normal persons.

Growth factor, on the other hand, has provided the potential for treatment of malignant or chronic wounds by inducing the activity of various cells. Growth factors regulate many of the factors needed for cellular activity such as cell division and migration, neovascularization during the course of treatment. Growth factors involved in this process include epidermal growth factor (EGF), platelet derived growth factor (PDGF), fibroblast growth factor (FGF), keratinocyte growth factor (KGF), transforming growth factor- (granulocyte colony stimulating factor), and vascular endothelial growth factor (VEGF).

Normal wound healing can be accomplished through a combination of sequential processes, such as cell migration and proliferation, and induction of extracellular matrix (ECM) deposition. If a problem arises in some of the above procedures, chronic inflammation may continue and a pathological inflammatory reaction may continue. Common causes of chronic ulcers include ischemia, diabetes, venous congestion, unnecessary pressure on the wound, and more than one cause can work simultaneously.

In the wound healing process, a variety of factors such as inflammatory mediators, growth factors, and cytokines act in a complex manner, and although inflammatory responses are essential for wound healing, excessive inflammatory responses may delay wound healing.

Therefore, when the expression of various factors affecting the inflammatory reaction is controlled, the wound healing process can be more smoothly performed.

As a result of efforts to find a natural herb medicine substance having less side effects in order to ameliorate a wound healing disorder caused by an excessive inflammatory reaction, the present inventors have found that a curd leaf currant extract can effectively control the wound healing process by controlling early inflammatory factors, To provide medical and food applications of the natural extract.

Disclosure of Invention Technical Problem [8] Accordingly, the present invention has been made keeping in mind the above problems occurring in the prior art, and an object of the present invention is to provide a composition for wound healing derived from natural materials, which exhibits excellent wound healing promoting effects while minimizing side effects.

According to an aspect of the invention, a round leaf Ipomoea Quamoclit (Quamoclit angulata Bojer ) extract as an active ingredient.

In one embodiment, the extract may be extracted with water, alcohol, ethyl acetate, acetone, hexane, dichloromethane or a mixed solvent thereof.

In one embodiment, the alcohol may be ethanol at a concentration of 40 to 70% (v / v).

In one embodiment, the composition is capable of inhibiting an early inflammatory factor.

In one embodiment, the composition can inhibit the expression of tumor necrosis factor alpha (TNF-alpha) and cyclooxygenase-2 (COX-2).

According to another aspect of the invention, a round leaf Ipomoea Quamoclit (Quamoclit angulata Bojer ) extract as an active ingredient.

According to another aspect of the invention, a round leaf Ipomoea Quamoclit (Quamoclit angulata A composition for improving diabetic wound healing disorders comprising an extract of Bojer as an active ingredient is provided.

According to one aspect of the present invention, by using a natural leaf extract of Curcuma pseudo-acacia var. Umbraculifera as a food or a pharmaceutical composition, side effects that may be caused by artificial materials such as chemicals can be minimized and wound healing can be significantly promoted.

It should be understood that the effects of the present invention are not limited to the effects described above, but include all effects that can be deduced from the description of the invention or the composition of the invention set forth in the claims.

FIG. 1 shows the wound healing effect of Curly Leaf Leaf Extract according to an embodiment of the present invention in a diabetes induction model.
FIG. 2 is a graph showing changes in the expression level of inflammatory cytokines associated with wound healing according to the administration of the extract of Curly-leaved Root Leaves according to an embodiment of the present invention.
FIGS. 3 and 4 will observe wound healing effects of the Curly Leaf Leaf Extract according to one embodiment of the present invention in a normal model.

As used herein, the terminology used herein is intended to encompass all commonly used generic terms that may be considered while considering the functionality of the present invention, but this may vary depending upon the intent or circumstance of the skilled artisan, the emergence of new technology, and the like. Also, in certain cases, there may be a term selected arbitrarily by the applicant, in which case the meaning thereof will be described in detail in the description of the corresponding invention. Therefore, the term used in the present invention should be defined based on the meaning of the term, not on the name of a simple term, but on the entire contents of the present invention.

Unless defined otherwise, all terms used herein, including technical or scientific terms, have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. Terms such as those defined in commonly used dictionaries are to be interpreted as having a meaning consistent with the contextual meaning of the related art and are to be interpreted as either ideal or overly formal in the sense of the present application Do not.

The numerical range includes numerical values defined in the above range. All numerical limitations of all the maximum numerical values given throughout this specification include all lower numerical limitations as the lower numerical limitations are explicitly stated. All the minimum numerical limitations given throughout this specification include all higher numerical limitations as the higher numerical limitations are explicitly stated. All numerical limitations given throughout this specification will include any better numerical range within a broader numerical range, as narrower numerical limitations are explicitly stated.

Hereinafter, embodiments of the present invention will be described in detail, but it should be apparent that the present invention is not limited by the following examples.

According to an aspect of the invention, a round leaf Ipomoea Quamoclit (Quamoclit angulata Bojer extract as an active ingredient is provided. According to another aspect, there is provided a composition for improving a diabetic wound healing disorder.

The above-mentioned Quamoclit angulata Bojer ) is a vinegared herbaceous herbaceous plant of the monocotyledonous plants of the monocotyledonous plants. It is native to tropical America and is mainly cultivated for ornamental purposes. The vine has the characteristic of growing like a morning glory and lifting it to the left. The present invention relates to a method for the treatment of wound healing, which comprises the steps of:

The wound healing can be accompanied by a complex, dynamic but well coordinated series of phenomena, including inflammation, new tissue formation and tissue remodeling. The wound healing is initiated at the moment of tissue damage and requires precise co-operation of epithelialization and skin recovery, among which the epithelialization process ultimately depends on the migration, proliferation, and differentiation capabilities of keratinocytes (Singer and Clark, 1999).

During epithelialization, keratinocytes located around the wound may migrate and proliferate to form a monolayer on the wound.

The wound healing process, in which damaged tissue restores its original structure and function, can be driven by normal cellular responses such as inflammatory mediators, growth factors, cytokines, and physical forces. The wound healing process consists of inflammation, proliferation, and regeneration. Platelet dividing growth factor (PDGF), transforming growth factor-β (VGF) and vascular endothelial growth factor (VEGF) The same growth factors are secreted and involved in the initiation of wound healing.

Inflammatory factors such as tumor necrosis factor α (TNF-α) secreted during the inflammatory phase activate NF-κB (nuclear factor kappa B), which is sensitive to oxidative stress, and are involved in the expression of inflammatory response factors.

Although inflammatory responses are essential in wound healing, excessive inflammatory responses can delay wound healing.

In particular, diabetes, which characterizes chronic hyperglycemia resulting from insulin secretion defects or defects in insulin action, can cause chronic complications and various complications, and can be used to restore wound and ischemic tissue damage The secretion of essential angiogenesis or various inflammatory cytokines, which are essentially required, may not be adequately controlled.

That is, the non-specific proteolytic inhibitor d2 polymer globulin referred to as 'tissue inhibitor of MMP' in normal wounds can inhibit overexpression of MMP-8 and neutrophil-derived elastase, but abnormally balanced If it is not maintained, damage to the wound may persist.

In addition, inflammatory cytokines such as TNF-α are increased due to excessive inflammatory cells caused by diabetes, PDGF promoting the transition to the proliferative phase, and TGF-β involved in the matrix deposition decrease, .

At this time, the above-mentioned Quamoclit angulata Bojer extract as an active ingredient can inhibit or regulate excessive early inflammatory factors and specifically inhibit or inhibit TNF-alpha and TNF-alpha by IL-1β and other growth factors, such as pro-inflammatory cytokines Induced expression of COX-2 (cyclooxygenase-2) can be effectively inhibited.

Thus, the composition can affect various factors including the initial inflammatory factor, thereby remarkably accelerating the wound healing, and effectively improving the wound healing disorder delayed by diabetes mellitus.

The inventors of the present invention have uncovered the use of the above-mentioned Curly Leaves as a food or medical material in order to promote wound healing and to ameliorate diabetic wound healing disorders.

The above-mentioned Curly Leaf Root Root Extract is easy to manufacture and easy to be taken by various processing methods such as capsules. In addition, wound healing can be significantly improved if a round leaf blade is used for a person who has delayed wound healing such as diabetic patients.

The above-mentioned " for wound healing " is intended for improvement of wounds or promotion of wound healing. The wound healing means improvement of the rate of relaxation of pathological phenomenon, generation of pathological cells or reduction of degree of loss or loss of cells. That is, when the pharmaceutical composition is used, the wound healing or recovery phenomenon can be accelerated as compared with the usual case. The improvement of the wound or the promotion of wound healing may be used in a generic sense to improve the recovery speed of the wound site and may include the meaning of a conventionally used treatment.

The above-mentioned " for the improvement of diabetic wound healing disorder " refers to an application for alleviating the delay of wound healing caused by diabetes and accelerating the wound healing rate by affecting a mechanism related to wound healing.

Unlike the chemical substances and the like, the above-mentioned Curly Leaf Root Extract is a substance derived from natural materials and is harmless to the human body, so that occurrence of fatal side effects due to ingestion or administration can be minimized.

The " extract " refers to a solvent in which an effective ingredient contained in an extracting material is transferred by contacting a solvent and an extracting material under specific conditions. The extract may contain an active ingredient in the raw material by an extraction process on a coral reef.

The kind of the solvent in the extraction step is not particularly limited, and various solvents may be used as needed. In addition, the extraction can be carried out using a conventional method in the art such as cold-rolling, warming, heating, and the like using the solvent.

For example, the above-mentioned Curly Leaf Root Extract may be extracted by using an ultrasonic extractor using a solvent selected from the group consisting of water, alcohol, aqueous alcohol solution, organic solvent or mixed solution for 2 to 3 days for 15 minutes every 2 hours . The extract can be obtained by concentrating the extract with vacuum rotary evaporator at room temperature and then lyophilizing the extracted residue.

In addition, the above-obtained Curly Leaf Root Extract can be passed through a column packed with activated charcoal to adsorb the active ingredient of the curd leaf, and the column packed with activated carbon can be washed with distilled water to remove non-adsorbed components. An organic solvent such as ethanol in an amount of 10 to 70% (v / v) is continuously or stepwise supplied to an activated carbon filling column from which the non-adsorbed component has been removed, and the active ingredient of the round- The extract may also be obtained.

The extract may be extracted with water, alcohol, ethyl acetate, acetone, hexane, dichloromethane or a mixed solvent thereof, preferably ethanol at a concentration of 40 to 70% (v / v).

The extraction ratio of the active ingredient contained in the raw material may be different depending on the polarity of the solvent. Since the ethanol has excellent selectivity in the extraction of the physiologically active substance of the herbal medicine, the ethanol extraction may improve the wound healing promoting effect have.

When ethanol is used as the extraction solvent, it is not only harmful to the human body but also suitable for use as a material for foods and pharmaceuticals, and it does not cause cost increase such as strict process control for securing stability. Therefore, You can also enhance it.

In addition, water and ethanol have different polarities, and the effective ingredient to be extracted according to each polarity may be different, so that the ethanol concentration can be appropriately controlled so that an optimal wound healing effect can be realized. However, if the concentration of ethanol is more than 70% (v / v), an adequate yield may not be realized. If the concentration is less than 40% (v / v), the active ingredient exhibiting wound healing promoting effect may not be sufficiently extracted The concentration of the solvent can be appropriately adjusted within the above range.

The pharmaceutical compositions may be administered in the form of oral delivery, parenteral delivery. The pharmaceutical composition may be administered systemically or topically, and the administration may include oral administration and parenteral administration. When the pharmaceutical composition is administered as a therapeutic, it may be formulated with a suitable amount of a pharmaceutically acceptable vehicle or carrier to provide a suitable dosage form.

Thus, the pharmaceutical composition may further comprise a carrier, excipient and diluent used in the preparation of the pharmaceutical composition

Examples of the carrier, excipient and diluent include lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, acacia rubber, alginate, gelatin, calcium phosphate, calcium silicate, cellulose, methylcellulose, microcrystalline cellulose, But are not limited to, polyvinylpyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate or mineral oil.

In addition, the composition may be formulated in the form of oral, granule, tablet, capsule, suspension, emulsion, syrup, aerosol or the like, external preparation, suppository and sterilized injection solution.

The solid preparation for oral administration includes a tablet, a pill, a powder, a granule, a capsule, etc., and the solid preparation comprises at least one excipient such as starch, calcium carbonate, sucrose, , Lactose, or gelatin. In addition to the above excipients, lubricants such as magnesium stearate and talc may also be used.

Examples of the liquid preparation for oral administration include suspensions, solutions, emulsions, syrups, and the like. In addition to water and liquid paraffin, simple diluents, various excipients such as wetting agents, sweeteners, have.

The preparation for parenteral administration may be a sterilized aqueous solution, a non-aqueous solvent, a suspension, an emulsion, a lyophilized preparation, or a suppository. Examples of the non-aqueous solvent and suspensions may include injectable esters such as propylene glycol, polyethylene glycol, vegetable oil such as olive oil and ethyl oleate. Examples of the suppository base include witepsol, macrogol, tween 61, cacao butter, laurin, and glycerogelatin.

A pharmaceutically effective amount of the pharmaceutical composition comprising the Curly Leaf Root Extract may be administered to a subject. The " pharmaceutically effective amount " means an amount sufficient to treat the disease at a reasonable benefit / risk ratio applicable to the medical treatment, and the effective dosage level will depend on the type of disease, severity, activity of the drug, Sensitivity, time of administration, route of administration and rate of excretion, duration of treatment, factors including co-administered drugs, and other factors well known in the medical arts.

The pharmaceutical composition may be administered as an individual therapeutic agent or in combination with other therapeutic agents, and may be administered sequentially or simultaneously with conventional therapeutic agents, and may be administered singly or in multiple doses. It is desirable to administer an amount that allows for all of the above factors to be maximally effected in a minimal amount without side effects, which can be readily determined by one skilled in the art.

According to another aspect of the invention, a round leaf Ipomoea Quamoclit (Quamoclit angulata Bojer ) extract as an active ingredient.

The food composition may include, but is not limited to, meat, snacks, dairy products, and beverages, and may include all conventional health functional foods.

The health functional food refers to a food prepared and processed by using a raw material or a component having a useful function in the human body according to the Health Functional Food Act No. 6727. The functional property refers to the nutrient Or for the purpose of obtaining a beneficial effect for health use such as physiological action.

The food composition may contain conventional food additives and, unless otherwise specified, may be prepared according to the standard and standard for the relevant item in accordance with the general provisions of the Food Additives Ordinance approved by the Food and Drug Administration and the General Test Methods It can be judged whether it is suitable or not. The food additives described in the above-mentioned Food Additives Code include chemical compounds such as ketones, glycine, potassium citrate, nicotinic acid, and cinnamic acid, natural additives such as persimmon extract, licorice extract, crystalline cellulose, high- A preservative formulation, a tar coloring agent, and the like.

The food composition can be used for various foods and beverages for promoting wound healing, and can be used for various foods, beverages, gums, tea, vitamin complex, health functional supplement, food additives, and the like.

The food composition may include 1.0 to 10.0% by weight of the Curd leaf fungus extract based on the total weight for the purpose of promoting wound healing of the subject. If the amount of the curd leaf fruiting root extract is less than 1.0% by weight, the effect of promoting wound healing may not be realized sufficiently, and if it exceeds 10.0% by weight, the original quality of the product may not be realized or cost efficiency may be deteriorated.

In addition, the food composition may be manufactured and processed into any one form selected from the group consisting of tablets, granules, powders, capsules, liquid solutions and rings for the purpose of promoting wound healing of the subject.

Specifically, the food composition in the form of tablets may be prepared by granulating a mixture of a curd leaf fungus extract, an excipient, a binder, a disintegrant and other additives by a conventional method, and then compressing the mixture by a lubricant or the like, Can be produced by molding. In addition, the food composition in the form of tablets may contain a starch or the like as needed, and may be encapsulated in a suitable skin care agent, if necessary.

The capsule form of the hard capsule may be prepared by filling a normal hard capsule with a mixture with an additive such as a curd leaf extract and an excipient, or by granulating or granulating the granule or granule. The soft capsule may be prepared by extracting a curd leaf, And the like can be filled in a capsule base such as gelatin. The soft capsule may contain a plasticizer such as glycerin or sorbitol, a coloring agent, a preservative and the like, if necessary.

The food composition of the present invention can be prepared by molding a mixture of a curd leaf curd leaf extract, an excipient, a binder and a disintegrating agent in an appropriate manner. If necessary, the food composition may be coated with white sugar or other suitable skin care agent, The substance may be irritated.

The granular food composition may be prepared by granulating a mixture of a curd leaf currant, an excipient, a binder, a disintegrant and the like by a suitable method, and if necessary, a flavoring agent, a starch, and the like.

The definitions of the above excipients, binders, disintegrants, lubricants, detergents, flavorings and the like may be those described in documents known in the art and include the same or similar functions.

Hereinafter, embodiments of the present invention will be described in detail with reference to the accompanying drawings, but it should be apparent that the present invention is not limited by the following embodiments.

Production Example: Preparation of Curly Leaf Root Root Extract

After washing with water, the dried leaf was completely dried at room temperature and then pulverized to obtain 100 g of pulverized material.

100 g of the pulverized product of the curly leaf furrow was extracted with a 10-fold volume of an aqueous ethanol solution (50% mass concentration) as a solvent at a temperature of 50 DEG C for 12 hours. The extract was filtered by a filter, and the extract was repeatedly extracted three times in the same manner for the remaining raw materials. The extract was concentrated under reduced pressure at 30 DEG C and lyophilized to give a solid.

Experimental Example  One : Curled leaf  Evaluation of wound healing rate by administration of extracts (diabetes induction model)

Alloxan (150 mg / kg) dissolved in saline solution was injected intraperitoneally into the ICR mouse. After 1 week, fasting blood glucose level of 250 mg / dL or higher was judged to be diabetic.

10 mg of Curly Leaf Leaf Extract of Preparation Example 1 was dissolved in 1 kg of sterilized distilled water for 3 weeks and a certain amount of the diabetic mice was orally administered for 4 weeks.

After the last administration, the anesthetized rats were deprived of their back and a wound of 4 mm in diameter was formed on the skin under the scapula. The wound healing rate was analyzed by taking the wound area at the same time every day and calculating the wound area.

At this time, the test group in which the diabetes was not induced was designated as the normal group (NC), the test group in which the diabetes was induced was designated as the diabetes mellitus (DMC), and the test group in which the diabetes mellitus- (DM + QL), and the pharmacological effect of the extract was tested.

Referring to FIG. 1, the wound was recovered at a significantly faster rate than the normal group (DMC) and the diabetic group (DMC) in the case of the foliar application group (DM + QL).

That is, in the case of diabetic group in which the sex treatment oil was delayed, the wound healing rate was remarkably increased by the administration of the curly leaf hyphae extract, and the wound area recovered faster than the normal group.

The above results suggest that the extract of Curcuma pseudo-acacia var. Orientalis from natural products can not only effectively promote wound healing but also has an excellent effect for improving diabetic wound healing disorders.

Experimental Example 2: Expression of Inflammatory Factor according to Administration of Curcuma longa Leaf Extract

Distilled water was administered to the normal group (NC) and diabetic group (DMC), and a part of the diabetic group (DM + QL)

The wounds on the skin of the mouse were formed and the wounds were recovered and the wounds were extracted and subjected to western blotting. The expression levels of TNF-alpha and COX-2 (cyclooxygenase-2) related to inflammation were measured through the western blot.

2, the expression of TNF-α and COX-2 was significantly lower in the group of the foliar application (DM + QL) than that of the normal group (NC) and the diabetes group (DMC).

That is, the Curly Leaf Extract of Curly Leaf can down-regulate the activity of factors involved in inflammation and alleviate the state of excessive inflammation until the end of wound healing, thereby effectively improving and promoting wound healing. Suggesting that the extract may be usefully used as an improvement of wound healing.

EXPERIMENTAL EXAMPLE 3 Evaluation of Wound Healing Rate According to the Administration of Curly Leaf Extract (Normal Model)

The skin of the mouse was wounded, and the normal leaf extract (Q) was orally administered to the control group (NC) for 14 days in the normal administration group (Q).

The rate of wound healing over time was compared, and the ratio of wound size was calculated by considering the wound size of the wound on day 1 as a relative reduction ratio.

Referring to FIGS. 3 and 4, the wound healing rate was significantly increased in the normal administration group treated with the extract of Curly Leaves.

These results suggest that the extract of Curcuma longa leaf can effectively promote recovery of the wound not only in the model with diabetes but also in the normal model.

It will be understood by those skilled in the art that the foregoing description of the present invention is for illustrative purposes only and that those of ordinary skill in the art can readily understand that various changes and modifications may be made without departing from the spirit or essential characteristics of the present invention. will be. It is therefore to be understood that the above-described embodiments are illustrative in all aspects and not restrictive. For example, each component described as a single entity may be distributed and implemented, and components described as being distributed may also be implemented in a combined form.

The scope of the present invention is defined by the appended claims, and all changes or modifications derived from the meaning and scope of the claims and their equivalents should be construed as being included within the scope of the present invention.

Claims (7)

Quamoclit angulata Bojer ) extract as an active ingredient. The method according to claim 1,
Wherein the extract is extracted with water, alcohol, ethyl acetate, acetone, hexane, dichloromethane or a mixed solvent thereof. 3. The method of claim 2,
Wherein the alcohol is ethanol at a concentration of 40 to 70% (v / v). The method according to claim 1,
A pharmaceutical composition for inhibiting an initial inflammatory factor. 5. The method of claim 4,
TNF-alpha (tumor necrosis factor alpha) and COX-2 (cyclooxygenase-2). Quamoclit angulata Bojer ) extract as an active ingredient. Quamoclit angulata Bojer ) extract as an active ingredient for improving diabetic wound healing disorders.

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