KR20140090756A - Pharmaceutical composition for preventing or treating inflammation or skin aging and cosmetic composition for improving inflammation or skin aging - Google Patents

Pharmaceutical composition for preventing or treating inflammation or skin aging and cosmetic composition for improving inflammation or skin aging Download PDF

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Publication number
KR20140090756A
KR20140090756A KR1020130002747A KR20130002747A KR20140090756A KR 20140090756 A KR20140090756 A KR 20140090756A KR 1020130002747 A KR1020130002747 A KR 1020130002747A KR 20130002747 A KR20130002747 A KR 20130002747A KR 20140090756 A KR20140090756 A KR 20140090756A
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South Korea
Prior art keywords
inflammation
skin
aging
pharmaceutical composition
cosmetic composition
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KR1020130002747A
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Korean (ko)
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KR102041803B1 (en
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한장희
이경진
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(주) 수파드엘릭사
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/64—Proteins; Peptides; Derivatives or degradation products thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/04—Peptides having up to 20 amino acids in a fully defined sequence; Derivatives thereof
    • A61K38/06—Tripeptides
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q19/00—Preparations for care of the skin
    • A61Q19/08—Anti-ageing preparations

Abstract

The present invention provides a pharmaceutical composition for preventing or treating inflammation or skin-aging, wherein the pharmaceutical composition includes small peptide fragments derived from a TNFR as an active ingredient. Moreover, the present invention provides a cosmetic composition for alleviating inflammation and skin-aging, wherein the cosmetic composition includes the peptide fragments. The peptide has anti-inflammatory activities by controlling the expression of various inflammation-mediated molecules and the extravasation of leukocytes. Moreover, the expression of MMP-1, TNF-α, and IL-1α, which are inflammation-mediated factors increased by ultraviolet ray stimulation and transcriptionally controlled by NF-κB, is controlled, and the generation of PGE_2, which is an inflammation-mediated molecule, and the expression of COX-2, which is an enzyme for mediating the same, are controlled, so that the composition has activities for controlling skin photoaging.

Description

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

The present invention relates to a pharmaceutical composition for preventing or treating inflammation or aging of skin comprising, as an active ingredient, small peptide fragments derived from a TNF receptor (TNFR). The present invention also relates to a cosmetic composition for improving inflammation or skin aging 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 and TNF-α. These inflammation-inducing molecules promote the expression of bFGF in keratinocytes. As a result, bFGF induces excessive proliferation of keratinocytes and melanocytes, Thickening and pigmentation occur. In addition, IL-1 and TNF-α activate NF-κB, a transcription factor in fibroblasts, resulting in degradation of 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 it has been surprisingly found that certain peptide fragments derived from specific regions of TNFR can inhibit the inflammatory response by modulating the function of TNFR, And have excellent inhibitory activity against skin inflammation and skin aging which are closely related to TNFR mediated inflammation.

Accordingly, it is an object of the present invention to provide a pharmaceutical composition for preventing or treating inflammation or skin aging comprising a specific peptide fragment derived from TNFR as an active ingredient.

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

According to one aspect of the present invention, there is provided a pharmaceutical composition for preventing or treating inflammation or aging of skin comprising, as an active ingredient, a peptide composed of the amino acid sequence of SEQ ID NO: 1 or a peptide composed of the amino acid sequence of SEQ ID NO:

According to another aspect of the present invention there is provided a cosmetic composition for improving inflammation or skin aging 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:

In the composition according to the present invention, the inflammation may be skin inflammation, preferably skin inflammation due to ultraviolet radiation. In addition, the aging of the skin may be skin photoaging, and may be skin photoaging by ultraviolet stimulation.

It has been found that certain peptide fragments derived from TNFR according to the present invention can inhibit the inflammatory response by modulating the function of TNFR and also have excellent inhibitory activity against skin inflammation and skin aging. Therefore, the peptide can be usefully applied to a pharmaceutical composition for preventing or treating inflammation or aging of the skin, and a cosmetic composition for improving inflammation or aging of the skin.

1 shows the results of evaluating the in vivo mononuclear extravasation inhibitory activity of the peptides according to the present invention.
FIGS. 2 and 3 show the results of evaluating MMP-1 expression in human dermal fibroblasts when treated with a peptide according to the present invention.

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 TNFR, and includes 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 skin inflammation due to ultraviolet rays.

"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.

The present invention provides a pharmaceutical composition for preventing or treating inflammation or aging of skin 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.

The present invention also provides a cosmetic composition for improving inflammation or skin aging 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.

The peptide according to the present invention has anti-inflammatory activity by inhibiting the expression of various inflammatory mediators that are induced by TNFR 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.

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 can be administered to a patient suffering from various inflammatory diseases or skin aging patients 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 skin aging-inhibiting effect, for example, an amount of 0.001 to 10% by weight based on the total weight of the composition, preferably about 0.01 To 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 TNFR-pep1 SEQ ID NO: 1 His-Leu-Leu TNFR-pep2 SEQ ID NO: 2 Ser-Lys-Glu

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. Monocyte In vivo ( in vivo ) Extravasation  Inhibition test

20 μl of 250 μM PMA (phorbol-12-myristate-13-acetate) was administered to one ear of 6-8 week old ICR mice and the other ear was treated with olive oil 20 [mu] l of acetone (1: 4) (O / A) was treated. After 3-4 hours 35 L- [S] - methionine-labeled in rat mononuclear cells WEHI274.1 1X10 6 was injected into the tail vein of the ICR mice. At this time, the peptide of the present invention was also injected at 100 占 퐂 / mice. After 1 hour of cell injection, ear tissue was taken at a constant size and the dose was measured with a scintillation counter. For quantitative experiments, at least three mice per group were used.

As can be seen from FIG. 1, when the peptide according to the present invention was treated, the number of monocytes outflowed into the blood vessels was markedly reduced. 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. People In dermal fibroblasts MMP -1 expression evaluation

MMP-1, which is induced by ultraviolet stimulation in human dermal fibroblasts, is known to decompose glue fibers to promote skin photoaging including wrinkle formation. Since MMP-1 is induced to express by NF-κB activation, it was evaluated using human dermal fibroblast Detroit 551 (ATCC CCL-110, USA) whether the expression of the peptide was inhibited by treatment with the peptide of the present invention.

Human dermal fibroblasts were treated with TNF-alpha (10 [mu] g / ml) and peptides 1, 10, and 100 [mu] M of SEQ ID NOS: 1 and 2. 48 hours later, cell extracts were subjected to Western blotting analysis to measure changes in the expression level of MMP-1. The results are shown in FIG. 2 and FIG. As can be seen in FIGS. 2 and 3, the expression level of MMP-1 was decreased in a concentration-dependent manner by the peptides of SEQ ID NOS: 1 and 2. Therefore, it can be confirmed that the peptide according to the present invention can inhibit aging of the skin by inhibiting the expression and function of collagen-degrading enzyme.

&Lt; 110 > SupadElixir Inc. <120> Pharmaceutical composition for or treating          inflammation or skin aging and cosmetic composition for improving          inflammation or skin aging <130> PN0625 <160> 2 <170> Kopatentin 2.0 <210> 1 <211> 3 <212> PRT <213> Artificial Sequence <220> <223> Peptide fragment <400> 1 His Leu Leu   One <210> 2 <211> 3 <212> PRT <213> Artificial Sequence <220> <223> Peptide fragment <400> 2 Ser Lys Glu   One

Claims (10)

A pharmaceutical composition for preventing or treating inflammation or skin aging, which comprises 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. The pharmaceutical composition according to claim 1, wherein the inflammation is skin inflammation. The pharmaceutical composition according to claim 2, wherein the inflammation is skin inflammation due to ultraviolet rays. The pharmaceutical composition according to claim 1, wherein the skin aging is skin photoaging. The pharmaceutical composition according to claim 4, wherein the skin aging is skin photo-aging caused by ultraviolet stimulation. 1. A cosmetic composition for improving inflammation or aging of skin 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: The cosmetic composition according to claim 6, wherein the inflammation is skin inflammation. The cosmetic composition according to claim 7, wherein the inflammation is skin inflammation caused by ultraviolet rays. The cosmetic composition according to claim 6, wherein the skin aging is skin photo-aging. The cosmetic composition according to claim 9, wherein the skin aging is skin photo-aging caused by ultraviolet stimulation.
KR1020130002747A 2013-01-10 2013-01-10 Pharmaceutical composition for preventing or treating inflammation or skin aging and cosmetic composition for improving inflammation or skin aging KR102041803B1 (en)

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Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2017074059A1 (en) * 2015-10-27 2017-05-04 차의과학대학교 산학협력단 Novel peptide and cosmetic composition comprising same for preventing skin aging or skin wrinkle formation
KR20170106168A (en) * 2016-03-09 2017-09-20 주식회사 바이오펩 Peptides for treating inflammatory diseases and use thereof

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2007039394A (en) * 2005-08-04 2007-02-15 Nippon Menaade Keshohin Kk External preparation for skin for preventing and ameliorating aging
KR20100093622A (en) * 2005-11-10 2010-08-26 더 유니버시티 오브 노쓰 캐롤라이나 엣 채플 힐 Splice switching oligomers for tnf superfamily receptors and their use in treatment of disease
KR20120105450A (en) * 2009-10-23 2012-09-25 비씨엔 펩티드즈, 에스.에이. Peptides used in the treatment and/or care of the skin, mucous membranes and/or hair and its use in cosmetic or pharmaceutical compositions
JP2012523836A (en) * 2009-04-17 2012-10-11 ニューヨーク ユニバーシティ Peptides that target TNF family receptors and antagonize TNF action, compositions, methods and uses thereof

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2007039394A (en) * 2005-08-04 2007-02-15 Nippon Menaade Keshohin Kk External preparation for skin for preventing and ameliorating aging
KR20100093622A (en) * 2005-11-10 2010-08-26 더 유니버시티 오브 노쓰 캐롤라이나 엣 채플 힐 Splice switching oligomers for tnf superfamily receptors and their use in treatment of disease
JP2012523836A (en) * 2009-04-17 2012-10-11 ニューヨーク ユニバーシティ Peptides that target TNF family receptors and antagonize TNF action, compositions, methods and uses thereof
KR20120105450A (en) * 2009-10-23 2012-09-25 비씨엔 펩티드즈, 에스.에이. Peptides used in the treatment and/or care of the skin, mucous membranes and/or hair and its use in cosmetic or pharmaceutical compositions

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2017074059A1 (en) * 2015-10-27 2017-05-04 차의과학대학교 산학협력단 Novel peptide and cosmetic composition comprising same for preventing skin aging or skin wrinkle formation
US10478392B2 (en) 2015-10-27 2019-11-19 College Of Medicine Pochon Cha University Industry-Academic Cooperation Foundation Peptide and cosmetic composition comprising same for preventing skin aging or skin wrinkle formation
KR20170106168A (en) * 2016-03-09 2017-09-20 주식회사 바이오펩 Peptides for treating inflammatory diseases and use thereof

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