KR20140090757A - Pharmaceutical composition for preventing or treating inflammation or allergy and cosmetic composition for improving inflammation or allergy - Google Patents

Abstract

The present invention provides a pharmaceutical composition for preventing or treating inflammation or allergy comprising small peptide fragments derived from IL-1R as an active ingredient. The present invention also provides a cosmetic composition for improving inflammation or allergy comprising the peptide fragment. The peptide has anti-inflammatory activity by inhibiting expression of various inflammatory mediators that are induced by NF-κB activation and inhibiting leukocyte extravasation. In addition, the peptide fragments effectively inhibit the IgE-mediated immediate hypersensitivity reaction, thereby having an excellent inhibitory activity against inflammation and allergy caused by hypersensitivity reaction.

Description

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a pharmaceutical composition for preventing or treating inflammation or allergy, and a cosmetic composition for improving inflammation or allergy,

The present invention relates to a pharmaceutical composition for preventing or treating inflammation or allergy comprising small peptide fragments derived from IL-1R (interleukin-1 receptor) as an active ingredient. The present invention also relates to a cosmetic composition for improving inflammation or allergy comprising the peptide fragment.

Inflammatory reactions are collectively referred to as defensive reactions of the body to restore the structure and function of tissues damaged by infection, trauma, and the like. Mobilization of leukocyte cells to the site of inflammation is important for rapid resolution of infection and for repair of tissue damage resulting from various traumas. However, erroneous or persistent inflammatory reactions cause damage and disease of the human body. For example, inflammatory diseases are caused by infections caused by bacteria or viruses such as cerebrospinal meningitis, enteritis, dermatitis, uveitis, encephalitis, adult respiratory distress syndrome, and non-infective factors such as trauma, autoimmune diseases and organ transplant rejection. Inflammatory diseases are classified as acute and chronic inflammatory diseases, which have different symptoms and pathological features. Local symptoms of acute inflammation such as allergies, bacterial and viral infections are caused by changes in blood flow and blood vessel size, changes in vascular permeability, and leukocyte infiltration. On the other hand, rheumatoid arthritis, atherosclerosis. The main pathological features of chronic inflammation, including chronic nephritis and cirrhosis, are that inflammatory factors are not eliminated and the infiltration of mononuclear cells, neutrophils, lymphocytes and plasma cells continues to infiltrate, resulting in chronic inflammation.

Inflammatory mediators, such as cytokines, chemokines, active oxygen intermediates, cyclooxygenase-2, COX-2, 5-lipoxygenase (5- lipoxygenase, 5-LOX) and matrix metalloproteinase (MMP) play an important role in the development and maintenance of the inflammatory reaction. Expression of these inflammatory mediators is induced by the transcription factors NF-κB (nuclear factor κB), STAT3 (signal transducer and activator of transcription 3), AP-1 (activator protein 1) and HIF-1a (hypoxia-inducible factor 1a) It is known to be regulated.

Ultraviolet light induces the secretion of inflammatory cytokines such as IL-1. These inflammation-inducing molecules promote the expression of bFGF in keratinocytes. As a result, bFGF induces excessive proliferation of keratinocytes and melanocytes, Lt; / RTI > IL-1, in turn, activates NF-κB, a transcription factor in fibroblasts, resulting in the degradation of the glial or elastic fibers of the dermis by promoting the production of proteolytic enzymes such as MMP-1 or MMP-9. As such, ultraviolet rays induce an inflammatory reaction in the skin. As a result, the aging phenomenon such as skin thickening, pigmentation and dermatophytic degradation caused by wrinkle formation or skin relaxation is promoted.

The present inventors have conducted various studies to search for small peptide fragments having an anti-inflammatory activity and therapeutic activity. In particular, the present inventors have designed a variety of small peptide fragments capable of inhibiting the function of inflammatory mediators and, surprisingly, certain peptide fragments derived from specific sites of IL-1R inhibit the inflammatory response by modulating IL- And have excellent inhibitory activity against skin inflammation and skin aging which are closely related to IL-1R mediated inflammation. In addition, it has been found that the peptide fragments effectively inhibit the IgE-mediated immediate hypersensitivity reaction and thus have an excellent inhibitory activity against inflammation and allergy caused by hypersensitivity reaction.

Accordingly, it is an object of the present invention to provide a pharmaceutical composition for preventing or treating inflammation or allergy comprising a specific peptide fragment derived from IL-1R as an active ingredient.

It is another object of the present invention to provide a cosmetic composition for improving inflammation or allergy comprising the specific peptide fragment.

According to one aspect of the present invention, there is provided a pharmaceutical composition comprising a peptide consisting of the amino acid sequence of SEQ ID NO: 1 or a peptide consisting of the amino acid sequence of SEQ ID NO: 2 as an active ingredient, A pharmaceutical composition is provided.

According to another aspect of the present invention, there is provided a cosmetic composition for improving inflammation or allergy comprising, as an active ingredient, a peptide consisting of the amino acid sequence of SEQ ID NO: 1 or a peptide composed of the amino acid sequence of SEQ ID NO: 2.

In the composition according to the present invention, the inflammation may be skin inflammation, preferably inflammation caused by an hypersensitivity reaction. In addition, the allergy may be an immediate hypersensitivity mediated by immunoglobulin E (IgE).

It has been found that certain peptide fragments derived from IL-1R according to the present invention can inhibit the inflammatory response by modulating the transcriptional promoting function of NF-κB, and have an excellent inhibitory activity against skin inflammation and skin aging. It has also been found that the peptide inhibits IgE-mediated immediate hypersensitivity thereby having an excellent inhibitory activity against inflammation and allergies induced by hypersensitivity. Therefore, the peptide can be usefully applied to pharmaceutical compositions for the prevention or treatment of inflammation or allergy, and cosmetic compositions for improving inflammation or allergy.

Figure 1 shows the in vitro ( in vitro ) mononuclear leukocyte release inhibitory activity.
Figure 2 shows the results of assessing the effect of peptides according to the present invention on IgE-mediated immediate hypersensitivity.

As used herein, the term "inflammation" includes without limitation inflammatory responses in the human body. Refers to an inflammatory response that is preferably activated by IL-1R, including acute and / or chronic inflammatory diseases; And inflammatory diseases (e.g., rheumatoid arthritis, osteoarthritis, etc.). The term "inflammation" includes skin inflammation (i.e., dermatitis) due to various causes, and preferably includes inflammation caused by an hypersensitivity reaction.

"Skin aging" refers to aging of the skin, including wrinkling of the skin, caused by intrinsic and external factors, and may preferably be skin photoaging accompanied by skin wrinkling, Includes skin photoaging by ultraviolet stimulation accompanied by skin wrinkling. In one embodiment, the skin aging comprises wrinkle formation on skin, i.e., skin wrinkles.

Also, in the present specification, the term "allergy" refers to type 1 hypersensitivity reactions (immediate hypersensitivity mediated by IgE) to environmental antigens. The peptide of the present invention is useful for preventing or treating delayed type hypersensitivity such as asthma, allergic rhinitis, atopic dermatitis, food allergy, Particularly preferably asthma, allergic rhinitis, atopic dermatitis and food allergy.

The present invention provides a pharmaceutical composition for preventing or treating inflammation or allergy comprising a peptide consisting of the amino acid sequence of SEQ ID NO: 1 or a peptide consisting of the amino acid sequence of SEQ ID NO: 2 as an active ingredient and a pharmaceutically acceptable carrier do.

In addition, the present invention provides a cosmetic composition for improving inflammation or allergy comprising, as an active ingredient, a peptide consisting of the amino acid sequence of SEQ ID NO: 1 or a peptide composed of the amino acid sequence of SEQ ID NO: 2.

The peptide according to the present invention has an anti-inflammatory activity by inhibiting expression of various inflammatory mediators that are induced by IL-1R and inhibiting leukocyte extravasation. Further, the PGE ₂ as an inflammatory mediator factor is increased by UV light stimulation, suppress transcription that inflammatory mediators of MMP-1, the expression of TNF-α, and IL-1α by NF-κB and inflammatory mediator molecule And suppresses the expression of COX-2, an enzyme that mediates the production and the mediating action, thereby having skin photoaging inhibition activity. In addition, the peptides inhibit the IgE-mediated immediate hypersensitivity, thereby having an excellent inhibitory activity against inflammation and allergy caused by hypersensitivity.

The pharmaceutical composition of the present invention may contain an excipient such as lactose, corn starch, a lubricant such as magnesium stearate, a known emulsifier, a suspending agent, a buffer, an isotonic agent, etc., And may be formulated into parenteral administration forms containing external preparations for skin. For intramuscular, intraperitoneal, subcutaneous, and intravenous dosage forms, it may usually comprise a buffer which is capable of producing a sterile solution of the active ingredient and suitably adjusting the pH of the solution, and may be isotonic Lt; / RTI > The pharmaceutical composition of the present invention may also be in the form of an aqueous solution comprising a pharmaceutically acceptable carrier such as a saline solution having a pH of 7.4 and can be introduced locally into the intramuscular blood stream of the patient in the form of a solution have. In addition, it can be formulated into a transdermal dosage form such as a solution for external use, an emulsion, an ointment, a patch or the like according to a conventional pharmaceutical method. The pharmaceutical composition of the present invention may be administered to a patient suffering from various inflammatory or allergic diseases at a dose of about 1 to 2000 mg / kg per day. Appropriate dosages can generally vary depending on the age, weight and symptoms of the patient.

The cosmetic composition of the present invention may be in the form of a functional cosmetic composition containing the peptide as an active ingredient. The cosmetic composition may be manufactured in various forms according to a conventional cosmetic preparation method. For example, the cosmetic composition may be prepared in the form of a cosmetic product containing the peptide, a lotion, a cream, a lotion or the like, which may be diluted with a conventional cleansing solution, a converging solution and a moisturizing solution. The cosmetic composition may also contain conventional adjuvants such as stabilizers, solubilizers, vitamins, pigments, and flavorings commonly used in the cosmetic composition arts. In the cosmetic composition, the content of the peptide may be an amount effective to achieve an inflammation or an allergy-suppressing effect, for example, an amount of 0.001 to 10% by weight based on the total weight of the composition, 1% by weight.

Hereinafter, the present invention will be described in more detail through examples and test examples. However, these examples and test examples are for illustrating the present invention, and the present invention is not limited to these examples and test examples.

Example  One. Of peptide  synthesis

Peptides of SEQ ID NOS: 1 and 2 were synthesized by the FMOC solid-phase method using an automated synthesizer (PeptrEx-R48, Peptron, Daejeon, Korea). The synthesized peptides were purified and analyzed by reversed-phase high-performance liquid chromatography (RP-20AB, Prominence LC-20AB, Shimadzu, Japan) using a C18 analysis RP column (Shiseido capcell pak) LC / MSD, Hewlett-Packard, Roseville, USA).

Peptide name SEQ ID NO: Amino acid sequence IL1R-pep1 SEQ ID NO: 1 Gly-Trp-Tyr IL1R-pep2 SEQ ID NO: 2 Trp-Tyr-Lys

Example  2. Peptides  Preparation of a Composition Containing

Peptides of SEQ ID NOS: 1 and 2 were dissolved in PBS, respectively, to make a concentration of 1 M. The resulting protein solution was used in the following test examples.

Test Example  1. In vitro test of monocytes in vitro ) Extravasation  Inhibition test

BEND3 (ATCC, USA), a rat brain stem cell, was cultured in a wicker chamber of a Boyden chamber. The culture supernatant was removed and pretreated with the peptide solution (100 μM) of SEQ ID NOs: 1 and 2 prepared in Example 2 or pretreated with mouse monocyte WEHI247.1 (ATCC, USA) was added to each treatment 5 x 10 ⁵ were added to each. In this case, NIH / 3T3, a mouse fibroblast, was cultured in DMEM serum-free medium supplemented with 0.005% vitamin C and 0.1% bovine serum albumin for 16 hours, and then centrifuged to obtain a supernatant containing monocyte infiltration Respectively. The cells were infiltrated into the lower chamber while being cultured for 6 hours, and the number of transferred cells was measured. The test was repeated 5 times and the results are shown in Fig.

As can be seen from FIG. 1, when the peptide of the present invention was treated, the number of mononuclear cells extruded out of the blood vessels was significantly decreased (about 60% level) as compared with the control group. Considering that leukocytes migrate along the blood vessels and then flow out of blood vessels in order to move to inflammation sites, the peptides of the present invention are expected to have an effective inhibitory activity against inflammation.

Test Example  2. IgE -Mediate immediate hypersensitivity ( IgE - mediated immediate 감성성  reactions inhibition test

The tail vein of six - week - old male Balb / c mice was sensitized by injecting 5 ㎍ of IgE antibody. After 24 hours, the peptide fragment of SEQ ID NO: 2 obtained in Example 1 was dissolved in 100 쨉 l of physiological saline and was administered peritoneally at a concentration of 10 mg / kg per mouse. Using a solution of 2,4-dinitrofluorobenzene (DNFB) dissolved at a concentration of 0.15% in a mixture of acetone and olive oil (4: 1, v / v) as an antigen, IgE-mediated immediate hypersensitivity by applying the solution to the ear Respectively. Negative control mice were injected with 100 μl of physiological saline and treated with DNFB. Positive control mice were injected with 100 μl of physiological saline and treated with DNFB. After 3 and 6 hours, digital calipers were used to measure changes in ear thickness. From day 1 after the peptide treatment, the peptide fragments of SEQ ID NO: 2 were injected intraperitoneally to the test group mice at a dose of 10 mg / kg, and the control group mice received intraperitoneal injections of physiological saline alone to compare the ear thickness changes for 3 days.

FIG. 2 is a graph showing changes in the ear thickness of the test group and the positive control group which were increased by DNFB treatment compared to the negative control group. From the results shown in Fig. 2, it can be seen that the ear thickness is significantly reduced when the peptide fragment according to the present invention is injected, as compared with the positive control. Therefore, the peptide of the present invention is expected to effectively inhibit the IgE-mediated immediate hypersensitivity reaction and effectively inhibit the inflammation induced by hypersensitivity reaction.

&Lt; 110 > SupadElixir Inc. <120> Pharmaceutical composition for or treating          inflammation or allergy and cosmetic composition for improving          inflammation or allergy <130> PN0626 <160> 2 <170> Kopatentin 2.0 <210> 1 <211> 3 <212> PRT <213> Artificial Sequence <220> <223> Peptide fragment <400> 1 Gly Trp Tyr   One <210> 2 <211> 3 <212> PRT <213> Artificial Sequence <220> <223> Peptide fragment <400> 2 Trp Tyr Lys   One

Claims (8)

A pharmaceutical composition for preventing or treating inflammation or allergy comprising a peptide consisting of the amino acid sequence of SEQ ID NO: 1 or a peptide consisting of the amino acid sequence of SEQ ID NO: 2 as an active ingredient, and a pharmaceutically acceptable carrier. The pharmaceutical composition according to claim 1, wherein the inflammation is skin inflammation. 3. The pharmaceutical composition according to claim 2, wherein the inflammation is inflammation caused by an hypersensitivity reaction. 2. The pharmaceutical composition according to claim 1, wherein said allergen is immediate hypersensitivity mediated by immunoglobulin E (IgE). A peptide consisting of the amino acid sequence of SEQ ID NO: 1 or a peptide composed of the amino acid sequence of SEQ ID NO: 2 as an active ingredient. The cosmetic composition according to claim 5, wherein the inflammation is skin inflammation. The cosmetic composition according to claim 6, wherein the inflammation is inflammation caused by an hypersensitivity reaction. 6. The cosmetic composition according to claim 5, wherein the allergen is immediate hypersensitivity mediated by immunoglobulin E (IgE).

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