KR20180090614A - Composition for preventing or improving diseases associated with inflammation containing glucose - Google Patents

Abstract

The present invention relates to a composition including glucose for preventing or ameliorating inflammation-related diseases. The composition according to one aspect exhibits a TRPV1 antagonist-like effect through suppression of neuronal excitement of neurons by opening of TREK1 or opening of TREK1 at pH 6.0-8.0, thereby preventing or ameliorating inflammation-related diseases or pain.

Description

TECHNICAL FIELD [0001] The present invention relates to a composition for preventing or ameliorating inflammation-related diseases including glucose,

And a composition for preventing or ameliorating inflammation-related diseases including glucose.

The transient receptor potential (TRP) ion channel is known to function as a sensing molecule capable of sensing various stimuli such as redox or osmotic pressure, temperature change, and regulating the homeostasis of the living body. Among them, transient receptor potential vanilloid 1 (TRPV1) is a receptor for capsaicin (8-methyl-N-vanillyl-6-nonenamide), a major component of hot pepper. VR1 (vallinoid receptor 1) -1 (vallinoid receptor-like protein 1). The membrane protein, TRPV1, is activated by capsaicin and has been shown to induce pain due to the introduction of positive ions and the formation of membrane voltage to transmit the stimulus to the nervous system. TRPV1 is activated or sensitized not only by capsaicin but also by stimuli such as resiniferatoxin, heat, acid, anandamide, lipid metabolite, and the like. The activity of TRPV1 by endogenous / exogenous stimuli induces the release of neuropeptides such as substance P (P) and calcitonin gene-related peptide (CGRP) in neurons as well as transmission of noxious stimuli , Causing neurogenic inflammation. Therefore, TRPV1 can be used to treat and improve various skin diseases. That is, if a substance that is directly related to pain and inflammation and is an antagonist of TRPV1 which is a target substance of many diseases, or a substance that has an effect of inhibiting TRPV1, or a substance that acts on skin nerve endings distributed by TRPV1 to suppress nerve excitement, SubP, cGRP, and other inflammation-inducing substances.

Thymic stromal lymphopoietin (TSLP) was first detected in cultures of thymus stromal cells as an IL-7-like cytokine. TSLP is an important factor that regulates the immune response at the interface between the body and the environment (skin, respiratory, digestive, eye, etc.) and is mainly secreted from skin epidermal cells and skin epithelial cells. It also transmits an itch signal through TRPV1 located at the nerve end, and promotes the secretion of inflammatory cytokines including TSLP through the TRPV1 receptor.

The TREK channel is one of the two-pore-domain potassium channel (K2P) groups. It is widely distributed in the central nervous system, peripheral nervous system, gastrointestinal tract, skin, and is involved in temperature sensation. It plays a role. TREK-1, TREK-2, and TRAAK. The TREK-1 channel is a channel that responds to temperature, osmolarity, and mechanical stimuli, and is involved as a molecular sensor to sense pain. This channel is also highly distributed in small sensory neurons and is located with the TRPV1 channel.

Although TRPV1 antagonists have been extensively studied and developed, studies using natural products have been limited. In particular, TRPV1 receptor antagonists have been shown to release TREK-1 or other potassium channels, There is no known natural product that can produce an antagonist mimic effect. Under these circumstances, the present inventors paid attention to the possibility that TREK1 interacts with TRPV1 antagonist and tried to prevent, ameliorate, or treat inflammation-related diseases or pain by controlling the activity of TREK1 and TRPV1. As a result, Related disease or pain can be treated by using the above-mentioned method.

One aspect is to provide a cosmetic composition for preventing or ameliorating an inflammation-related disease, which comprises glucose and has a pH of 6.0-8.0.

Another aspect is to provide a quasi-drug composition for preventing or ameliorating inflammation-related diseases comprising glucose and having a pH of 6.0-8.0.

Another aspect is to provide a pharmaceutical composition for preventing or treating inflammation-related diseases, which comprises glucose and has a pH of 6.0-8.0.

One aspect includes glucose and provides a cosmetic composition for preventing or ameliorating an inflammation-related disease having a pH of 6.0-8.0.

The glucose may be contained in an amount of 0.1% by weight to 90% by weight, specifically 1% by weight to 70% by weight, more preferably 1% by weight to 50% by weight, based on the total weight of the cosmetic composition.

The glucose of the present invention exhibits an effect of preventing or ameliorating an inflammation-related disease or pain by effectively suppressing an inflammatory reaction, particularly a skin inflammatory reaction, at a pH range of pH 6.0-8.0.

The term " preventing " or " prevention " refers to a reduction in the risk of developing a disease or condition (i. E., A condition in which an individual who has not yet experienced the disease, To prevent what happens to be caused).

The pH of the cosmetic composition may be 6.0-8.0, specifically pH 6.5-7.5.

The glucose may exhibit a TRPV1 antagonist mimic effect. TRPV1 antagonists are agents that inhibit the action of TRPV1 receptors, which mediate the transmission of pain signals and mediate various inflammatory responses. A " TRPV1 antagonist-like effect " does not directly inhibit the action of the TRPV1 receptor by binding to the TRPV1 receptor, but can be determined by, for example, TRPV1, which is indicated by the suppression of neuronal excitations of neurons by K2P channels such as opening of TREKl or hyperpolarization due to TREKl opening It means an effect similar to antagonist.

The cosmetic composition may further comprise at least one member selected from the group consisting of ketone, polyunsaturated fatty acid, aloe vera, sodium bicarbonate, vitamin C, vitamin D, and vitamin D precursors.

In the present invention, the term " ketone body " is a generic name of three substances including acetoacetic acid,? -Hydroxybutyric acid and acetone produced by decarboxylation of the substance, and is mainly produced by oxidation of fatty acids in the liver. The ketone body may be contained in an amount of 0.1-10% by weight, preferably 1-5% by weight based on the total weight of the cosmetic composition, but is not limited thereto.

The term " polyunsaturated fatty acids (PUFAs) " in the present invention refers to unsaturated fatty acids having three or more carbon double bonds, and has both hydrophilic and lipophilic characteristics. Omega 3, Omega 6, which contains eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). Linoleic acid, linolenic acid, or arachidonic acid. The polyunsaturated fatty acid may be included in an amount of 0.1-10% by weight, preferably 1-5% by weight based on the total weight of the cosmetic composition, but is not limited thereto.

When the cosmetic composition further comprises a ketone or polyunsaturated fatty acid, the prevention, improvement, or therapeutic effect of the inflammation-related diseases of the composition can be maximized. For example, when the cosmetic composition further comprises a ketone body, the prevention, improvement, or therapeutic effect of an inflammation-related disease can be enhanced by opening a K2P channel such as TREK1 or opening of TREK1, When the composition further contains an unsaturated fatty acid, the prevention, the improvement, or the therapeutic effect of the inflammation-related disease can be enhanced by the reduction of glucose degradation.

The term " inflammation " refers to the pathological condition of abscesses formed by the infiltration of external infectious agents (bacteria, fungi, viruses, various kinds of allergens).

In the present invention, " inflammation-related diseases " may include without limitation diseases caused by inflammation, and may include, for example, pain or inflammatory skin diseases.

The pain may be selected from the group consisting of acute pain, chronic pain, neuropathic pain, postoperative pain, rheumatoid arthritis, osteoarthritic pain, postherpetic neuralgia, neuralgia, headache, toothache, pelvic pain, migraine, But are not limited to, one or more members selected from the group consisting of spinal cord, sprains, paresthesia, allodynia, and hyperalgesia.

Wherein the inflammatory skin disease is selected from the group consisting of psoriasis, pruritus, opacification, seborrheic dermatitis, contact dermatitis, atopic dermatitis, irritable lupus, allergic skin disease, urticaria, eczema, Including, but not limited to, species.

The cosmetic composition may be prepared by any conventional formulation, and examples thereof include softening agents, convergent lotion, nutritional lotion, nutritional cream, massage cream, essence, eye cream, eye essence, cleansing cream, cleansing foam, It may be formulated into at least one selected from the group consisting of water, a pack, a powder, a body lotion, a body cream, a body oil, a body essence, a makeup base, a foundation, a hair dye, a shampoo, a rinse and a body cleanser.

The cosmetic composition of the present invention may contain conventional auxiliaries and carriers such as antioxidants, stabilizers, solubilizers, vitamins, pigments and flavors which are conventionally used in addition to glucose, and may be formulated together with the carrier.

When the formulation of the cosmetic composition of the present invention is a paste, a cream or a gel, an animal oil, vegetable oil, wax, paraffin, starch, tracant, cellulose derivative, polyethylene glycol, silicone, bentonite, silica, talc or zinc oxide Can be used.

When the formulation of the cosmetic composition of the present invention is a powder or a spray, lactose, talc, silica, aluminum hydroxide, calcium silicate or polyamide powder may be used as a carrier component. Especially, in the case of a spray, Propellants such as carbon, propane / butane or dimethyl ether.

When the formulation of the cosmetic composition of the present invention is a solution or emulsion, a solvent, a dissolving agent or an emulsifying agent is used as a carrier component, and examples thereof include water, ethanol, isopropanol, ethyl carbonate, ethyl acetate, benzyl alcohol, benzyl benzoate, Glycol, 1,3-butyl glycol, glycerol aliphatic ester, polyethylene glycol or fatty acid esters of sorbitan.

When the formulation of the cosmetic composition of the present invention is a suspension, a carrier such as water, a liquid diluent such as ethanol or propylene glycol, a suspension such as ethoxylated isostearyl alcohol, polyoxyethylene sorbitol ester and polyoxyethylene sorbitan ester , Microcrystalline cellulose, aluminum metahydroxide, bentonite, agar or tracant, etc. may be used.

When the formulation of the cosmetic composition of the present invention is a surfactant-containing cleansing, the carrier component may include aliphatic alcohol sulfate, aliphatic alcohol ether sulfate, sulfosuccinic acid monoester, isethionate, imidazolinium derivative, methyltaurate, sarcosinate, Fatty acid amide ether sulfate, alkylamidobetaine, aliphatic alcohol, fatty acid glyceride, fatty acid diethanolamide, vegetable oil, lanolin derivative, or ethoxylated glycerol fatty acid ester.

In addition, the ingredients contained in the cosmetic composition may be included in an amount commonly used in the skin science field.

Another aspect includes glucose and provides quasi-compositions for the prevention or amelioration of an inflammatory disease with a pH of 6.0-8.0.

The glucose and inflammation-related diseases are as described above.

The term " quasi-drug " in the present invention means a fiber, a rubber product or the like used for the purpose of treating, alleviating, treating or preventing a disease of a human or an animal, Or products similar to those that are not machinery, and those used for sterilization, insecticide and similar uses for the prevention of infectious diseases, for the purpose of diagnosis, treatment, alleviation, treatment or prevention of diseases of human or animal. Machinery, or apparatus, and that is not an apparatus, machine or apparatus of an article used for the purpose of causing pharmacological effects on the structure or function of a person or animal.

The quasi-drug composition of the present invention is not limited thereto, but it is preferably used in the form of a sanitary napkin, a mask, an eyebrow, a bandage, an elastic bandage, a plaster bandage, a cylindrical elastic bandage, a gauze, Antiseptic, insect repellent, contact lens care product, smoking cessation aid, external disinfectant, ointment, cataplasm, anti-rheumatic agent, But is not limited to, at least one selected from the group consisting of a spray, a toothpaste, a tooth whitening agent, a humidifier sterilizing agent, a washing solution, and a cleansing solution.

When the quasi-drug composition of the present invention is used as a quasi-drug additive, the composition may be added as it is, or may be used together with other quasi-drugs or quasi-drugs, and may be suitably used according to a conventional method. The amount of the active ingredient to be mixed can be appropriately determined depending on the purpose of use.

Another aspect includes glucose and provides a pharmaceutical composition for the prevention or treatment of inflammation related diseases having a pH of 6.0-8.0.

The glucose and inflammation-related diseases are as described above.

The term "treatment" refers to or includes alleviation, inhibition or prevention of a disease, disorder or condition, or one or more symptoms thereof.

The pharmaceutical composition of the present invention can be administered parenterally or orally as a systemic administration. In the case of parenteral administration, it can be administered by intravenous infusion, intramuscular injection, or the like. The appropriate dosage of the pharmaceutical composition of the present invention may vary depending on such factors as formulation method, administration method, age, body weight, sex, pathological condition, food, administration time, route of administration, excretion rate, .

The pharmaceutical composition of the present invention may be administered in a pharmaceutically effective amount, the term "pharmaceutically effective amount" means an amount sufficient to treat a disease at a reasonable benefit / risk ratio applicable to medical treatment , Effective dose levels are well known in the species and severity, age, sex, activity of the drug, sensitivity to the drug, time of administration, route of administration and rate of release, duration of treatment, ≪ / RTI > The pharmaceutical composition of the present invention may be administered as an individual therapeutic agent or in combination with other therapeutic agents, and may be administered sequentially or simultaneously with a conventional therapeutic agent for inflammatory diseases. And can be administered singly or multiply. It is important to take into account all of the above factors and administer an amount that will achieve the maximum effect in the least amount without side effects.

In addition, the pharmaceutical composition of the present invention can be used alone or in combination with methods using surgery, hormone therapy, drug therapy and biological response modifiers for the treatment of inflammatory diseases occurring in the skin.

The composition according to one embodiment exhibits a TRPV1 antagonist-like effect through inhibition of neuronal excitations of neurons by opening of TREK1 or opening of TREK1 at pH 6.0-8.0, thereby preventing, ameliorating, or treating inflammation related diseases or pain It is effective.

Hereinafter, the present invention will be described in more detail with reference to examples. However, these examples are for illustrative purposes only, and the scope of the present invention is not limited to these examples.

Example  1: Check for pain relief

Twenty randomly selected subjects (double blind, controlled) were tested for the effects of glucose on pain relief according to pH conditions. Specifically, when the capsaicin sauce was applied to the lips for 5 minutes, or when the spicy (painful) symptom became 8 points or more on a scale of 10, the following four solutions (A, B, C, and D) And the duration of painful and painful pain relief is shown in Table 1 below.

A: 10% glucose, pH 4.3

B: 10% glucose, pH 7.2

C: 10% glucose, pH 8.1

D: saline solution

In this case, 500 ml of 10% glucose injection solution (CJ) was used as glucose solution, 100 ml of physiological saline solution (CJ) was used as a control group for neutralization of glucose solution.

A B C D % ¹ Seconds ² % second % second % second Male, 33 years old 60 5 90 20 70 10 60 15 W, 30 50 5 80 15 70 10 50 5 Male, 29 years old 30 5 60 15 40 10 30 5 Male, 34 years old 40 10 90 20 60 15 40 10 W, age 24 30 5 90 20 60 15 40 10 W, age 24 30 5 80 15 50 10 50 10 W, age 27 30 8 80 20 60 12 30 8 W, age 24 40 6 80 15 60 10 40 6 W, 33 30 5 80 20 50 10 30 5 Female, 29 years old 20 5 80 15 40 10 20 5 Male, 34 years old 40 10 90 20 60 15 40 10 W, 34 30 5 70 15 60 10 30 5 W, age 24 40 5 90 20 60 15 40 5 W, age 20 40 5 80 15 60 10 50 10 W, 26 30 5 90 15 70 10 30 5 Male, 39 years old 50 5 80 20 70 15 50 5 Male, 29 years old 30 5 80 20 70 15 30 5 W, 26 40 3 80 15 60 10 40 3 W, 34 40 5 70 15 70 10 50 5 Male, 35 years old 30 5 60 15 40 10 30 5 Average 40.5 6.2 88.8 19.1 65.5 12.8 43.3. 7.6

n = 20 (persons), ¹ degree of pain relief (%), ² duration of pain relief (second)

As shown in Table 1, the pain relieving degree of the solution B (pH 7.2) was 88% or more, and the pain relieving ability was the best, and the pain relieving duration was also 19 seconds or longer.

C solution (pH 8.1) showed excellent pain relieving effect compared to solution A (pH 4.3) or D solution (control). However, both the duration of pain relief and the degree of pain relief were similar to those of solution B It was confirmed that the pain relief effect was better. The reason for the weak pain relief effect in physiological saline or other solutions may be due to the dilution of the capsaicin by the solution or the cold temperature of the solution itself (15 ° C).

Thus, it was confirmed that when glucose was treated at neutral pH (pH 6.0-8.0), for example, pH 7.2, pain relieving effect was obtained.

Claims (8)

A cosmetic composition for preventing or ameliorating an inflammation-related disease comprising glucose and having a pH of 6.0-8.0. The cosmetic composition according to claim 1, further comprising at least one member selected from the group consisting of ketone bodies, polyunsaturated fatty acids, aloe vera, sodium bicarbonate, vitamin C, vitamin D, and vitamin D precursors. The cosmetic composition according to claim 1, wherein the inflammation related disease is pain or an inflammatory skin disease The method of claim 3, wherein the pain is selected from the group consisting of acute pain, chronic pain, neuropathic pain, postoperative pain, rheumatoid arthritis, osteoarthritic pain, postherpetic neuralgia, neuralgia, headache, toothache, pelvic pain, migraine, Wherein the composition is at least one selected from the group consisting of visceral pain, muscular pain, sprains, hypersensitivity, allodynia, and hyperalgesia. 4. The method of claim 3, wherein the inflammatory skin disease is selected from the group consisting of psoriasis, pruritus, dermatitis, seborrheic dermatitis, contact dermatitis, atopic dermatitis, irritable lupus, allergic skin disease, urticaria, eczema, Lt; RTI ID = 0.0 > 1, < / RTI > The cosmetic composition according to claim 1, wherein the glucose exhibits a TRIPV1 (transient receptor potential vanilloid 1) antagonistic effect. A quasi-drug composition for preventing or ameliorating an inflammation-related disorder comprising glucose and having a pH of 6.0-8.0. A pharmaceutical composition for preventing or treating an inflammation-related disease comprising glucose and having a pH of 6.0-8.0.