KR20100021641A - Skin compositions for exteral application containing thujae semen extract - Google Patents
Skin compositions for exteral application containing thujae semen extract Download PDFInfo
- Publication number
- KR20100021641A KR20100021641A KR1020100011765A KR20100011765A KR20100021641A KR 20100021641 A KR20100021641 A KR 20100021641A KR 1020100011765 A KR1020100011765 A KR 1020100011765A KR 20100011765 A KR20100011765 A KR 20100011765A KR 20100021641 A KR20100021641 A KR 20100021641A
- Authority
- KR
- South Korea
- Prior art keywords
- composition
- extract
- skin
- lymphocyte
- white porcelain
- Prior art date
Links
- 239000000203 mixture Substances 0.000 title claims abstract description 66
- 239000000284 extract Substances 0.000 title claims abstract description 40
- 210000000582 semen Anatomy 0.000 title abstract description 4
- 210000001744 T-lymphocyte Anatomy 0.000 claims abstract description 37
- 206010012438 Dermatitis atopic Diseases 0.000 claims abstract description 25
- 201000008937 atopic dermatitis Diseases 0.000 claims abstract description 25
- 230000001404 mediated effect Effects 0.000 claims abstract description 16
- 239000002537 cosmetic Substances 0.000 claims abstract description 12
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- 208000010247 contact dermatitis Diseases 0.000 claims abstract description 11
- 239000004480 active ingredient Substances 0.000 claims abstract description 10
- 229910052573 porcelain Inorganic materials 0.000 claims description 35
- 201000004681 Psoriasis Diseases 0.000 claims description 11
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- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 7
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- 102000004127 Cytokines Human genes 0.000 description 6
- 108090000695 Cytokines Proteins 0.000 description 6
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 6
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- 206010003645 Atopy Diseases 0.000 description 4
- 238000002965 ELISA Methods 0.000 description 4
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 4
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- VMGAPWLDMVPYIA-HIDZBRGKSA-N n'-amino-n-iminomethanimidamide Chemical compound N\N=C\N=N VMGAPWLDMVPYIA-HIDZBRGKSA-N 0.000 description 4
- BOLDJAUMGUJJKM-LSDHHAIUSA-N renifolin D Natural products CC(=C)[C@@H]1Cc2c(O)c(O)ccc2[C@H]1CC(=O)c3ccc(O)cc3O BOLDJAUMGUJJKM-LSDHHAIUSA-N 0.000 description 4
- 210000004989 spleen cell Anatomy 0.000 description 4
- 230000000699 topical effect Effects 0.000 description 4
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- 206010020751 Hypersensitivity Diseases 0.000 description 3
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- 208000010668 atopic eczema Diseases 0.000 description 3
- 239000003795 chemical substances by application Substances 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 239000003814 drug Substances 0.000 description 3
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- 230000004073 interleukin-2 production Effects 0.000 description 3
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- VBICKXHEKHSIBG-UHFFFAOYSA-N 1-monostearoylglycerol Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(O)CO VBICKXHEKHSIBG-UHFFFAOYSA-N 0.000 description 2
- WOVKYSAHUYNSMH-RRKCRQDMSA-N 5-bromodeoxyuridine Chemical compound C1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C(Br)=C1 WOVKYSAHUYNSMH-RRKCRQDMSA-N 0.000 description 2
- 208000001840 Dandruff Diseases 0.000 description 2
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 2
- KRHYYFGTRYWZRS-UHFFFAOYSA-N Fluorane Chemical compound F KRHYYFGTRYWZRS-UHFFFAOYSA-N 0.000 description 2
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
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- 229940079593 drug Drugs 0.000 description 2
- 229930182478 glucoside Natural products 0.000 description 2
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- 229960001340 histamine Drugs 0.000 description 2
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- 238000000338 in vitro Methods 0.000 description 2
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 2
- 230000007774 longterm Effects 0.000 description 2
- 239000002609 medium Substances 0.000 description 2
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 2
- GLDOVTGHNKAZLK-UHFFFAOYSA-N octadecan-1-ol Chemical compound CCCCCCCCCCCCCCCCCCO GLDOVTGHNKAZLK-UHFFFAOYSA-N 0.000 description 2
- 230000028327 secretion Effects 0.000 description 2
- 150000003431 steroids Chemical class 0.000 description 2
- 230000004936 stimulating effect Effects 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 230000008961 swelling Effects 0.000 description 2
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 2
- LBLYYCQCTBFVLH-UHFFFAOYSA-N 2-Methylbenzenesulfonic acid Chemical compound CC1=CC=CC=C1S(O)(=O)=O LBLYYCQCTBFVLH-UHFFFAOYSA-N 0.000 description 1
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 1
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 1
- 241001342895 Chorus Species 0.000 description 1
- 208000017667 Chronic Disease Diseases 0.000 description 1
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- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
- 208000010201 Exanthema Diseases 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 1
- 206010040880 Skin irritation Diseases 0.000 description 1
- 235000021355 Stearic acid Nutrition 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 1
- 230000006044 T cell activation Effects 0.000 description 1
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
- 210000004241 Th2 cell Anatomy 0.000 description 1
- GSEJCLTVZPLZKY-UHFFFAOYSA-N Triethanolamine Chemical compound OCCN(CCO)CCO GSEJCLTVZPLZKY-UHFFFAOYSA-N 0.000 description 1
- 230000002159 abnormal effect Effects 0.000 description 1
- 235000011054 acetic acid Nutrition 0.000 description 1
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- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 229940125715 antihistaminic agent Drugs 0.000 description 1
- 239000000739 antihistaminic agent Substances 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- 210000003719 b-lymphocyte Anatomy 0.000 description 1
- SRSXLGNVWSONIS-UHFFFAOYSA-N benzenesulfonic acid Chemical compound OS(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-N 0.000 description 1
- 229940092714 benzenesulfonic acid Drugs 0.000 description 1
- KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
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- HAORKNGNJCEJBX-UHFFFAOYSA-N cyprodinil Chemical compound N=1C(C)=CC(C2CC2)=NC=1NC1=CC=CC=C1 HAORKNGNJCEJBX-UHFFFAOYSA-N 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
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- 239000008187 granular material Substances 0.000 description 1
- 239000012676 herbal extract Substances 0.000 description 1
- 241000411851 herbal medicine Species 0.000 description 1
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- 239000003906 humectant Substances 0.000 description 1
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- 239000003018 immunosuppressive agent Substances 0.000 description 1
- 239000012535 impurity Substances 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 230000003780 keratinization Effects 0.000 description 1
- 239000004310 lactic acid Substances 0.000 description 1
- 235000014655 lactic acid Nutrition 0.000 description 1
- 230000021633 leukocyte mediated immunity Effects 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 210000004698 lymphocyte Anatomy 0.000 description 1
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
- 239000011976 maleic acid Substances 0.000 description 1
- 229940098779 methanesulfonic acid Drugs 0.000 description 1
- 239000003226 mitogen Substances 0.000 description 1
- 230000009456 molecular mechanism Effects 0.000 description 1
- GOQYKNQRPGWPLP-UHFFFAOYSA-N n-heptadecyl alcohol Natural products CCCCCCCCCCCCCCCCCO GOQYKNQRPGWPLP-UHFFFAOYSA-N 0.000 description 1
- PSZYNBSKGUBXEH-UHFFFAOYSA-N naphthalene-1-sulfonic acid Chemical compound C1=CC=C2C(S(=O)(=O)O)=CC=CC2=C1 PSZYNBSKGUBXEH-UHFFFAOYSA-N 0.000 description 1
- 229910017604 nitric acid Inorganic materials 0.000 description 1
- 235000016709 nutrition Nutrition 0.000 description 1
- 230000035764 nutrition Effects 0.000 description 1
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
- WWZKQHOCKIZLMA-UHFFFAOYSA-N octanoic acid Chemical compound CCCCCCCC(O)=O WWZKQHOCKIZLMA-UHFFFAOYSA-N 0.000 description 1
- 230000008506 pathogenesis Effects 0.000 description 1
- 229940100460 peg-100 stearate Drugs 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 230000002062 proliferating effect Effects 0.000 description 1
- 230000001737 promoting effect Effects 0.000 description 1
- 239000008213 purified water Substances 0.000 description 1
- MCJGNVYPOGVAJF-UHFFFAOYSA-N quinolin-8-ol Chemical compound C1=CN=C2C(O)=CC=CC2=C1 MCJGNVYPOGVAJF-UHFFFAOYSA-N 0.000 description 1
- 206010037844 rash Diseases 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 231100000475 skin irritation Toxicity 0.000 description 1
- 230000036556 skin irritation Effects 0.000 description 1
- 229940080352 sodium stearoyl lactylate Drugs 0.000 description 1
- ODFAPIRLUPAQCQ-UHFFFAOYSA-M sodium stearoyl lactylate Chemical compound [Na+].CCCCCCCCCCCCCCCCCC(=O)OC(C)C(=O)OC(C)C([O-])=O ODFAPIRLUPAQCQ-UHFFFAOYSA-M 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
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- 210000000952 spleen Anatomy 0.000 description 1
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- 239000008117 stearic acid Substances 0.000 description 1
- 208000011580 syndromic disease Diseases 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- YBRBMKDOPFTVDT-UHFFFAOYSA-N tert-butylamine Chemical compound CC(C)(C)N YBRBMKDOPFTVDT-UHFFFAOYSA-N 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 206010043778 thyroiditis Diseases 0.000 description 1
- 230000001256 tonic effect Effects 0.000 description 1
- 239000006211 transdermal dosage form Substances 0.000 description 1
- 150000003626 triacylglycerols Chemical class 0.000 description 1
- 235000013311 vegetables Nutrition 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- H—ELECTRICITY
- H02—GENERATION; CONVERSION OR DISTRIBUTION OF ELECTRIC POWER
- H02G—INSTALLATION OF ELECTRIC CABLES OR LINES, OR OF COMBINED OPTICAL AND ELECTRIC CABLES OR LINES
- H02G3/00—Installations of electric cables or lines or protective tubing therefor in or on buildings, equivalent structures or vehicles
- H02G3/02—Details
- H02G3/04—Protective tubing or conduits, e.g. cable ladders or cable troughs
- H02G3/0456—Ladders or other supports
-
- F—MECHANICAL ENGINEERING; LIGHTING; HEATING; WEAPONS; BLASTING
- F16—ENGINEERING ELEMENTS AND UNITS; GENERAL MEASURES FOR PRODUCING AND MAINTAINING EFFECTIVE FUNCTIONING OF MACHINES OR INSTALLATIONS; THERMAL INSULATION IN GENERAL
- F16B—DEVICES FOR FASTENING OR SECURING CONSTRUCTIONAL ELEMENTS OR MACHINE PARTS TOGETHER, e.g. NAILS, BOLTS, CIRCLIPS, CLAMPS, CLIPS OR WEDGES; JOINTS OR JOINTING
- F16B13/00—Dowels or other devices fastened in walls or the like by inserting them in holes made therein for that purpose
- F16B13/04—Dowels or other devices fastened in walls or the like by inserting them in holes made therein for that purpose with parts gripping in the hole or behind the reverse side of the wall after inserting from the front
- F16B13/08—Dowels or other devices fastened in walls or the like by inserting them in holes made therein for that purpose with parts gripping in the hole or behind the reverse side of the wall after inserting from the front with separate or non-separate gripping parts moved into their final position in relation to the body of the device without further manual operation
-
- H—ELECTRICITY
- H02—GENERATION; CONVERSION OR DISTRIBUTION OF ELECTRIC POWER
- H02G—INSTALLATION OF ELECTRIC CABLES OR LINES, OR OF COMBINED OPTICAL AND ELECTRIC CABLES OR LINES
- H02G3/00—Installations of electric cables or lines or protective tubing therefor in or on buildings, equivalent structures or vehicles
- H02G3/02—Details
- H02G3/04—Protective tubing or conduits, e.g. cable ladders or cable troughs
- H02G3/0406—Details thereof
-
- H—ELECTRICITY
- H02—GENERATION; CONVERSION OR DISTRIBUTION OF ELECTRIC POWER
- H02G—INSTALLATION OF ELECTRIC CABLES OR LINES, OR OF COMBINED OPTICAL AND ELECTRIC CABLES OR LINES
- H02G3/00—Installations of electric cables or lines or protective tubing therefor in or on buildings, equivalent structures or vehicles
- H02G3/30—Installations of cables or lines on walls, floors or ceilings
Landscapes
- Engineering & Computer Science (AREA)
- Architecture (AREA)
- Civil Engineering (AREA)
- Structural Engineering (AREA)
- General Engineering & Computer Science (AREA)
- Mechanical Engineering (AREA)
- Medicines Containing Plant Substances (AREA)
- Cosmetics (AREA)
Abstract
Description
본 발명은 본 발명은 생약재 추출물을 함유하는 피부 외용제 조성물에 관한 것으로, 더욱 상세하게는 백자인(Thujae Semen) 추출물을 함유하는 조성물에 관한 것이다. 본 발명의 피부 외용제 조성물은 T 임파구 매개성 면역반응에 의해 유발되는 각종 피부질환, 구체적으로 아토피성 피부염, 접촉성 피부염, 건선 등의 증상을 개선하고, 나아가 이들 피부질환의 치료 및 예방을 목적으로 사용될 수 있다.
The present invention relates to a composition for external application for skin containing herbal extracts, more specifically white porcelain ( Thujae Semen ) relates to a composition containing the extract. The external preparation composition for skin of the present invention improves the symptoms of various skin diseases caused by T lymphocyte mediated immune response, specifically atopic dermatitis, contact dermatitis, psoriasis, etc., and furthermore, for the treatment and prevention of these skin diseases. Can be used.
아토피성 피부염(Atopic Dermatitis)은 원인 불명의 강한 소양감, 건조함, 심한 각질 발생, 두부 인설(비듬), 홍반과 부어오름, 피부균열, 심한 진물과 습진, 태선화 등의 증상이 복합적으로 나타나는 피부의 이상 증후군이다. 많은 경우 10년 이상 지속되며 장기간 생활에 큰 불편을 끼치는 만성 질환이다. 예전에는 영아기나 유아기에 시작되어 성장과 함께 병세가 점점 개선되어 7~8세 이전에 사라지는 경우가 대부분이었다. 그러나 1970년대 이후 급격한 산업화로 유발된 공해, 환경오염 등으로 인해 발생률이 해마다 증가하고 있으며, 증상이 청소년기 및 성인기까지 지속되며 점점 심해지거나 청소년기 이후에 새롭게 발병하는 경우도 현저히 증가하고 있다. 강한 가려움증과 함께 피부염증을 동반하는 것이 증상의 특징이며, 히스타민의 과다 분비가 가려움증의 주요 원인이 된다. 가려움으로 인해 피부를 긁게 되면 홍반이나 습진성 병변이 나타나게 되고, 심할 경우 피부가 벗겨지거나 태선화(피부가 두꺼워지게 되는 현상)가 진행된다.Atopic Dermatitis is a complex of skin that is characterized by a combination of symptoms such as strong pruritus, dryness, severe keratinization, torn head, dandruff, erythema and swelling, skin cracks, severe rashes, eczema, and thyroiditis. It is an abnormal syndrome. In many cases, it is a chronic disease that lasts for more than 10 years and causes great inconvenience in long-term life. In the past, infants and infants started in the early stages of development and their condition gradually improved and disappeared before the age of 7-8 years. However, since the 1970s, the incidence rate has increased year by year due to the pollution and environmental pollution caused by the rapid industrialization, and the symptoms continue to adolescence and adulthood, and become more severe or newly developed after adolescence. Symptoms are accompanied by strong itching and skin irritation, and excessive secretion of histamine is a major cause of itching. When the skin is scratched due to itching, erythema or eczema appears, and in severe cases, the skin may be peeled off or the lichen may become thickened.
아토피성 피부염의 원인에 대해서는 최근까지 수많은 연구결과와 정보가 제시되었으나, 질환 자체의 복잡성과 서로 상충되는 연구 데이터들로 인해 정확한 병인과 유효한 치료법에 대해서 아직까지 명확한 이론이 확립되지 않은 상태이다. 이러한 문제점으로 인해 현재까지 개발되어 있는 아토피성 피부염 치료제는 스테로이드 제제, 경구용 항히스타민제, 히드록시퀴놀린(hydroxyquinoline), 타르 제제 및 저자극성 보습제 등 근본적인 치료보다는 증상을 적절한 수준으로 조절하는 데 도움을 주는 제품들이 주종을 이루고 있다. 그러나 현재까지 개발되어 있는 어떤 의약품도 환자들의 요구를 완전히 충족시켜주지 못하고 있는 실정이다. 최근까지는 국소용 스테로이드 제제가 아토피성 피부염 치료제의 주종을 차지하고 있으나, 장기간 사용시의 내성발현 및 안전성의 문제로 인해 부작용이 없고 보다 안전한 비스테로이드성 아토피성 피부염 치료제의 개발이 절실히 요구되고 있다.Many studies and information on the cause of atopic dermatitis have been presented until recently, but the exact pathology and effective treatment have not yet been established due to the complexity of the disease itself and conflicting research data. Due to these problems, the atopic dermatitis treatments that have been developed to date help to control symptoms to an appropriate level rather than the fundamental treatments such as steroid preparations, oral antihistamines, hydroxyquinoline, tar preparations, and hypoallergenic humectants. Products dominate. However, none of the drugs developed to date fully meet the needs of patients. Until recently, topical steroid preparations have been the main dominant agents for treating atopic dermatitis, but there is an urgent need for development of safer nonsteroidal atopic dermatitis treatments without side effects due to resistance expression and safety problems during long-term use.
최근에는 T 임파구의 활성과다 및 IgE의 과다 분비로 인한 과민반응과 같이 비정상적으로 활성화된 면역 반응이 아토피성 피부염, 접촉성 피부염, 건선 질환의 주된 원인 중 하나라는 사실이 밝혀짐에 따라, 과도한 면역 반응을 억제함으로써 이들 피부질환을 치료하려는 접근법이 관심을 모으고 있다.Recently, it has been found that abnormally activated immune responses, such as hyperactivity of T lymphocytes and hypersensitivity of IgE, are one of the main causes of atopic dermatitis, contact dermatitis, and psoriasis disease. Attempts to treat these skin diseases by suppressing the response have attracted attention.
T 세포 매개성 면역반응을 제어하는 사이토카인에는 여러 종류가 있지만, 특히 아토피성 피부염의 병리에서 중요한 역할을 담당하고 있는 것이 인터류킨-2와 인터류킨-4이다. 인터류킨-2는 T 세포 활성화의 초기 단계에 생산되어 Th 세포를 자극함으로써 면역반응을 강력하게 촉발하는 사이토카인이다.There are many types of cytokines that control T cell mediated immune responses, but interleukin-2 and interleukin-4 play important roles in the pathology of atopic dermatitis. Interleukin-2 is a cytokine produced in the early stages of T cell activation and strongly triggering an immune response by stimulating Th cells.
또한, 최근에 아토피성 피부염의 병인과 관련하여 커다란 관심을 모으고 있는 인터류킨-4는 T 세포 유형 중 특히 아토피성 피부염의 특징적인 병리현상인 Th2 세포의 불균형적인 활성증대를 유도한다는 사실이 밝혀져 있다. 동시에 인터류킨-4는 B 세포를 자극하여 IgE 생산을 증대시킴으로써 비만세포에 의한 히스타민 분비를 촉진하여 홍반, 발적, 가려움증 등의 아토피 반응을 유발하는 핵심 사이토카인이다. T 임파구의 활성과다, IgE의 과다 분비로 인한 과민반응과 같은 면역반응이 아토피성 피부염, 접촉성 피부염, 건선 질환과 관련이 있다는 사실을 기술하고 있는 문헌들이 알려지고 있다. [Leung D and Bieber T. Atopic Dermatitis. Lancet 2003, 361: 151-160], [Galli E, Cicconi R, Rossi P, Casati A, Brunetti E, and Mancino G. Atopic Dermatitis: Molecular Mechanisms, Clinical Aspects and New Therapeutical Approaches. Current Molecular Medicine 2003, 3: 127-138], [Christophers E. Psoriasis-epidemiology and clinical spectrum. Clinnical Experimental Dermatology 2001, 26(4): 314-320].In addition, it has been found that interleukin-4, which has recently been of great interest in the pathogenesis of atopic dermatitis, induces an imbalanced increase in Th2 cells, a characteristic pathology of atopic dermatitis, in particular. At the same time, interleukin-4 is a key cytokine that stimulates B cells to increase IgE production, thereby promoting histamine secretion by mast cells, leading to atopic reactions such as erythema, redness, and itching. Literature describing the fact that immune responses, such as hyperactivity of T lymphocytes and hypersensitivity from IgE, is associated with atopic dermatitis, contact dermatitis and psoriasis disease is known. Leung D and Bieber T. Atopic Dermatitis. Lancet 2003, 361: 151-160, Galli E, Cicconi R, Rossi P, Casati A, Brunetti E, and Mancino G. Atopic Dermatitis: Molecular Mechanisms, Clinical Aspects and New Therapeutical Approaches. Current Molecular Medicine 2003, 3: 127-138, Christophers E. Psoriasis-epidemiology and clinical spectrum. Clinnical Experimental Dermatology 2001, 26 (4): 314-320].
따라서, 인터류킨-2, 인터류킨-4의 생산 및 이들 사이토카인 반응의 최종 결과물인 T 세포의 과도한 증식을 동시에 억제할 수 있는 물질은 일반적인 면역억제 물질보다 아토피성 피부염의 치료에 더욱 적합한 효능을 제공할 수 있다는 것을 알 수 있다.
Thus, substances capable of simultaneously inhibiting the production of interleukin-2 and interleukin-4 and the final proliferation of T cells, the end result of these cytokine reactions, may provide better efficacy for the treatment of atopic dermatitis than common immunosuppressive agents. It can be seen that.
이에 본 발명자들은 피부에서 비정상적으로 활성화된 면역반응을 통제할 수 있는 방법을 탐색하던 중, 백자인 추출물이 T 임파구 매개성 면역반응의 핵심 사이토카인인 인터류킨-2(interleukin-2)와 IgE 생산을 자극하는 T 임파구 사이토카인인 인터류킨-4(interleukin-4)의 생산을 억제하고, 또한 T 임파구의 과도한 증식을 억제하는 효능을 갖고 있음을 발견하고 본 발명을 완성하게 되었다.The inventors explored ways to control abnormally activated immune responses in the skin, and white porcelain extract stimulates the production of interleukin-2 and IgE, the key cytokines of T lymphocyte-mediated immune responses. The present invention was found to have the effect of inhibiting the production of interleukin-4, which is a T lymphocyte cytokine, and also inhibiting excessive proliferation of T lymphocytes.
따라서, 본 발명의 목적은, 백자인 추출물을 유효성분으로 함유함으로써, 비정상적으로 활성화된T 임파구 매개성 면역반응을 억제하여 아토피성 피부염, 접촉성 피부염 및 건선의 증상을 개선할 수 있는 안전하고 유효한 피부 외용제 조성물을 제공하는 것이다.
Therefore, an object of the present invention, by containing the white porcelain extract as an active ingredient, by inhibiting abnormally activated T lymphocyte-mediated immune response, safe and effective skin that can improve the symptoms of atopic dermatitis, contact dermatitis and psoriasis It is to provide an external preparation composition.
상기한 목적을 달성하기 위하여, 본 발명은 백자인 추출물을 유효성분으로 함유하는 T 임파구 매개성 피부면역질환 개선용 화장료 조성물 및 약제학적 조성물을 제공한다.
In order to achieve the above object, the present invention provides a cosmetic composition and pharmaceutical composition for improving T lymphocyte-mediated skin immune disease containing white extract as an active ingredient.
본 발명에 의한 백자인 추출물을 함유하는 조성물은, 인터류킨-2 및 인터류킨-4의 생산을 억제하고 T 임파구의 분열증식을 억제함과 동시에 마우스 비장 임파구, 각질형성세포, 섬유아세포에 특기할 만한 독성을 나타내지 않았다. 따라서 본 발명에 의한 조성물은 매우 안전하면서도 T 임파구 매개성 면역반응을 효과적으로 억제하는 효과가 있다. 그러므로 과도한 T 임파구 매개성 면역반응에 관련된 피부질환인 아토피성피부염, 접촉성피부염, 건선 등을 치료 또는 예방할 수 있는 조성물로 이용될 수 있다.
The composition containing the extract of white porcelain according to the present invention inhibits the production of interleukin-2 and interleukin-4, inhibits the proliferation of T lymphocytes, and at the same time exhibits a particular toxicity to mouse spleen lymphocytes, keratinocytes and fibroblasts. Not shown. Therefore, the composition according to the present invention is very safe and effectively inhibits the T lymphocyte mediated immune response. Therefore, it can be used as a composition capable of treating or preventing atopic dermatitis, contact dermatitis, psoriasis and the like which are skin diseases related to excessive T lymphocyte mediated immune response.
본 발명에 따른 피부 외용제 조성물은 백자인 추출물을 유효성분으로 함유함을 특징으로 한다.The external preparation composition for skin according to the present invention is characterized by containing white porcelain extract as an active ingredient.
본 발명에 의한 피부 외용제 조성물에 있어서, 상기한 백자인 추출물은 전체 조성물 중에 0.001~10중량%, 바람직하게는 0.01~5중량%의 양으로 함유됨을 특징으로 한다.In the external preparation composition for skin according to the present invention, the extract of white porcelain is characterized in that it is contained in an amount of 0.001 to 10% by weight, preferably 0.01 to 5% by weight in the total composition.
본 발명의 피부 외용제 조성물은 T 임파구 매개성 면역반응에 의해 유발되는 각종 피부질환, 구체적으로 아토피성 피부염, 접촉성 피부염, 건선 등의 증상을 개선하고, 나아가 이들 피부질환의 치료 및 예방을 목적으로 사용될 수 있다. 이를 위하여 본 발명의 피부 외용제 조성물은, 상기 피부질환의 치료 및 예방을 목적으로 하는 약제학적 조성물로 제공될 수 있으며, 또한 상기 피부질환의 증상 개선을 목적으로 하는 기능성 화장료 조성물로 제공될 수 있다.The external preparation composition for skin of the present invention improves the symptoms of various skin diseases caused by T lymphocyte mediated immune response, specifically atopic dermatitis, contact dermatitis, psoriasis, etc., and furthermore, for the treatment and prevention of these skin diseases. Can be used. To this end, the external preparation composition for skin of the present invention may be provided as a pharmaceutical composition for the purpose of treating and preventing the skin disease, and may also be provided as a functional cosmetic composition for the purpose of improving the symptoms of the skin disease.
이하 본 발명을 더욱 구체적으로 설명한다.Hereinafter, the present invention will be described in more detail.
본 발명의 피부 외용제 조성물에 사용되는 백자인(Thujae Semen)은 측백나무과(Cupressaceae)의 상록교목인 측백나무 (Biota orientalis (L) ENDL)의 종인으로서 자양강장, 진정, 통변 등의 목적으로 사용된다. 또한, 예로부터 각종 질환의 증상 개선 및 치료를 목적으로 사용되어 왔으며, 인체에 대한 안전성이 검증된 생약재이다. Thujae Semen used in the topical skin composition of the present invention is an evergreen arboretum of Cupressaceae ( Biota) Orientalis (L) ENDL) is a species used for the purpose of nourishing tonic, soothing and stool. In addition, it has been used for the purpose of improving and treating the symptoms of various diseases since ancient times, and is a herbal medicine that has been proven to be safe for humans.
본 발명의 피부 외용제 조성물에 유효성분으로 사용되는 백자인 추출물은, 상기한 바와 같이 각종 질환의 증상 개선 및 치료에 대한 효능은 입증되어 있으나, 본 발명에서 목적하는 T 임파구 매개성 면역반응에 대한 억제 효능에 대해서는 전혀 알려진 바가 없으며, 이는 오직 본 발명에 의해 개시되는 것임을 명시하는 바이다. 특히, 백자인 추출물이 아토피성 피부염, 접촉성 피부염 및 건선의 주된 원인이 되는 인터류킨-2, 인터류킨-4의 생산 및 T 임파구의 과도한 증식을 억제하는 효능을 갖고 있음에 대해서는 전혀 알려진 바 없다.White porcelain extract, which is used as an active ingredient in the external preparation composition for skin of the present invention, has been shown to be effective in improving and treating symptoms of various diseases as described above, but has an inhibitory effect on T lymphocyte-mediated immune responses desired in the present invention. Is not known at all, and it is stated that this is only disclosed by the present invention. In particular, it is not known that white extracts have the effect of inhibiting the production of interleukin-2, interleukin-4 and excessive proliferation of T lymphocytes, which are the main causes of atopic dermatitis, contact dermatitis and psoriasis.
본 발명에서 상기 추출물의 사용량은 시험관내(in vitro) 실험을 근거로 조성물 총 중량에 대하여 0.001~10중량%, 바람직하게는 0.01~5중량%이다. 추출물 함량이 0.001중량% 미만이면 활성 성분으로서 작용을 기대하기 어려우며, 10중량%를 초과하면 제형 안정성에 문제가 생길 수 있다. 이러한 관점에서 더욱 바람직하게는 0.01~5중량%의 양으로 사용되는 것이 좋다.The amount of the extract used in the present invention is in vitro ( in In vitro ) based on the experiment is 0.001 to 10% by weight, preferably 0.01 to 5% by weight relative to the total weight of the composition. If the extract content is less than 0.001% by weight, it is difficult to expect to act as an active ingredient, and if the extract content is more than 10% by weight, problems with formulation stability may occur. From this point of view, more preferably used in an amount of 0.01 to 5% by weight.
본 발명에 의한 피부 외용제 조성물은, 본 발명이 목적하고 있는 아토피성 피부염, 접촉성 피부염 또는 건선 등의 피부질환의 증상 개선, 나아가 치료와 예방을 목적으로 사용될 수 있으며, 그 제형에 있어서는 특별히 한정되지 않는다. 본 발명의 피부 외용제 조성물은, 상기한 피부질환의 증상 개선을 목적으로 하는 기능성 화장료 조성물로 제공될 수 있으며, 또한 상기 피부질환의 치료 및 예방을 목적으로 하는 약제학적 조성물로 제공될 수 있다.The external preparation composition for skin according to the present invention can be used for the purpose of improving the symptoms of the skin diseases such as atopic dermatitis, contact dermatitis or psoriasis, further treatment and prevention, and the formulation is not particularly limited. Do not. The external preparation composition for skin of the present invention may be provided as a functional cosmetic composition for the purpose of improving the symptoms of the aforementioned skin diseases, and may also be provided as a pharmaceutical composition for the purpose of treating and preventing the skin diseases.
본 발명이 기능성 화장료 조성물로 제공되는 경우, 예를 들면, 유연화장수, 영양화장수, 마사지크림, 영양크림, 팩, 젤, 에센스 또는 피부 점착타입 화장료의 제형으로, 또는 로션, 연고, 겔, 크림, 패취 또는 분무제 등의 경피 투여형 제형으로 제제화될 수 있다.When the present invention is provided as a functional cosmetic composition, for example, in a soft cosmetics, nourishing cosmetics, massage creams, nutrition creams, packs, gels, essences or formulations of skin adhesive type cosmetics, or lotions, ointments, gels, creams, It may be formulated into a transdermal dosage form such as a patch or spray.
또, 본 발명이 약제학적 조성물로 제공되는 경우, 상기한 백자인 추출물은 추출물 그대로 또는 약학적으로 허용 가능한 염의 형태로 사용될 수 있다. 염으로는 약학적으로 허용되는 것이면 특별히 한정되지 않으며, 예를 들어 염산, 황산, 질산, 인산, 불화수소산, 브롬화수소산, 포름산, 아세트산, 타르타르산, 젖산, 시트르산, 푸마르산, 말레산, 숙신산, 메탄술폰산, 벤젠술폰산, 톨루엔술폰산, 나프탈렌술폰산 등에 의해 형성되는 산 부가염을 사용할 수 있다. 산 부가염 이외에도, 수산화나트륨, 수산화칼륨, 트리에틸아민, 3차-부틸아민과 같은 염기 부가염도 사용될 수 있다.In addition, when the present invention is provided in a pharmaceutical composition, the white porcelain extract may be used as it is or in the form of a pharmaceutically acceptable salt. The salt is not particularly limited as long as it is pharmaceutically acceptable, and for example, hydrochloric acid, sulfuric acid, nitric acid, phosphoric acid, hydrofluoric acid, hydrobromic acid, formic acid, acetic acid, tartaric acid, lactic acid, citric acid, fumaric acid, maleic acid, succinic acid, methanesulfonic acid , Acid addition salts formed by benzenesulfonic acid, toluenesulfonic acid, naphthalenesulfonic acid and the like can be used. In addition to acid addition salts, base addition salts such as sodium hydroxide, potassium hydroxide, triethylamine, tert-butylamine can also be used.
본 발명에 의한 약제학적 조성물은, 유효성분에 악영향을 미치지 않는 한, 필요에 따라 의약에 사용되는 각종 보조제, 예컨대 담체나 기타 첨가제, 예컨대 안정제, 완화제, 유화제 등을 첨가하여 제제화할 수 있다.The pharmaceutical composition according to the present invention can be formulated by adding various auxiliaries used in medicine, such as carriers or other additives such as stabilizers, emollients, emulsifiers and the like, as long as they do not adversely affect the active ingredient.
본 발명에 의한 약제학적 조성물에 있어서 상기한 백자인 추출물의 함유량은, 제형에 따라 광범위하게 변할 수 있으며 통상적인 방법에 따른다.In the pharmaceutical composition according to the present invention, the content of the extract of white porcelain described above may vary widely depending on the formulation and is in accordance with conventional methods.
본 발명에 의한 약제학적 조성물은 비경구 투여될 수 있으며, 경피 투여가 바람직하고, 특히 국소 도포가 가장 바람직하다. 국소 도포에 적절한 고체 또는 액체 부형제나 희석제를 이용하여 통상적인 방법으로 제형화할 수 있다. 예를 들면, 연고, 크림, 주사제, 산제, 과립제, 정제 등의 적합한 어떠한 제형으로도 할 수 있다.Pharmaceutical compositions according to the invention may be administered parenterally, transdermal administration is preferred, in particular topical application is most preferred. It may be formulated in a conventional manner using solid or liquid excipients or diluents suitable for topical application. For example, it may be any suitable formulation such as ointment, cream, injection, powder, granules, tablets and the like.
본 발명에 의한 약제학적 조성물의 투여량은 환자의 나이, 상태, 질환의 증상 정도에 따라 차이가 있으나, 바람직하게는, 0.001~1000㎎/ ㎏·day이다.The dosage of the pharmaceutical composition according to the present invention varies depending on the age, condition, and degree of disease of the patient, but preferably, it is 0.001 to 1000 mg / kg · day.
본 발명에 의한 약제학적 조성물은 단독으로 투여되거나 다른 약제와 동등하게 또는 다른 약제를 보조하기 위해 함께 투여될 수 있다.The pharmaceutical compositions according to the invention can be administered alone or in combination with other agents or together to assist other agents.
또한, 각 제형의 외용제 조성물에 있어서, 상기한 필수 성분 이외의 다른 성분들은 기타 외용제의 제형 또는 사용목적 등에 따라 당업자가 적의 선정하여 배합할 수 있다.
In addition, in the external preparation composition of each formulation, other components other than the above-mentioned essential components can be suitably selected and blended by those skilled in the art according to the formulation of the external preparation or the purpose of use.
이하, 실시예 및 시험예를 들어 본 발명의 구성 및 작용효과를 보다 구체적으로 설명한다. 그러나, 본 발명이 이들 예로만 한정되는 것은 아니다.
Hereinafter, the configuration and effect of the present invention will be described in more detail with reference to Examples and Test Examples. However, the present invention is not limited only to these examples.
<< 실시예Example 1> 백자인 추출물의 조제 1> Preparation of White Porcelain Extract
백자인 1㎏을 건조분쇄한 후 중량(㎏)비 4배량의 95% 에탄올을 가한 후 80℃에서 2시간 가열하여 유효성분을 추출하였다. 이를 하루동안 상온에서 방치하여 불순물을 침전시킨 후, 여과지를 이용하여 2회 여과한 여액을 감압 증발기를 사용하여 완전히 증발시켜 농축하였다.
After drying 1 kg of white porcelain, 95% ethanol was added at a ratio of 4 times by weight (kg), and then heated at 80 ° C. for 2 hours to extract an active ingredient. This was allowed to stand at room temperature for 1 day to precipitate impurities, and the filtrate was filtered twice using a filter paper and concentrated by completely evaporating using a reduced pressure evaporator.
<< 시험예Test Example 1> 1> 인터류킨Interleukin -2 생산 억제 효과-2 production inhibitory effect
BALB/C 생쥐의 비장세포에 T 임파구를 자극하여 반응을 일으키는 미토젠 (mitogen)인 콘카나발린 A(concanavalin A)를 가한 다음, 상기 실시예 1에서 제조된 추출물을 각각 처리하여 인터류킨-2의 생산 억제 효과를 측정하였다.Concanavalin A, a mitogen that reacts by stimulating T lymphocytes to splenocytes of BALB / C mice, was added, followed by treatment of the extracts prepared in Example 1, respectively. The production inhibitory effect was measured.
상세히 말하자면, 10%의 우태아 혈청이 함유된 RPMI배지가 함유된 96공 평판배양기(96-well microtiter plate)에 생쥐의 비장세포를 200,000 세포/웰이 되도록 넣고, 콘카나발린 A를 2㎍/㎖ 농도로 가하여 T 임파구를 활성화시켰다. 그 다음 각 조성물을 하기 표 1의 농도대로 처리하여 24시간 후에 배양액 중으로 유리된 인터류킨-2를 ELISA(Enzyme-Linked Immunosorbent Assay) 방법으로 정량하였다. 이때 콘카나발린 A만을 처리하고 조성물을 처리하지 않은 군을 대조군으로 하여 하기 수학식 1에 따라 인터류킨-2 생산 억제율을 계산하여 그 결과를 표 1에 나타내었다.Specifically, the mouse's splenocytes were added to 200,000 cells / well in a 96-well microtiter plate containing 10% fetal bovine serum RPMI medium, and 2 μg / conconnavaline A was added. A ml concentration was added to activate T lymphocytes. Each composition was then treated according to the concentration of Table 1 below, and after 24 hours, the interleukin-2 released into the culture was quantified by ELISA (Enzyme-Linked Immunosorbent Assay) method. At this time, using only the concanavalin A and not treated with the composition as a control group to calculate the interleukin-2 production inhibition rate according to Equation 1 shown in Table 1 below.
상기 표 1에 나타난 바와 같이, 본 발명의 백자인 추출물은 각각 0.001%의 낮은 농도에서 활성화된 T 임파구에 의한 인터류킨-2의 생산을 억제하는 효과를 갖고 있음을 알 수 있었다.
As shown in Table 1, the white porcelain extract of the present invention was found to have an effect of inhibiting the production of interleukin-2 by activated T lymphocytes at low concentrations of 0.001%, respectively.
<< 시험예Test Example 2> 2> 인터류킨Interleukin -4 생산 억제 효과-4 production inhibitory effect
BALB/C 생쥐의 비장세포에 콘카나발린 A를 가한 다음, 상기 실시예 1에서 제조된 백자인 추출물을 처리하여 인터류킨-4의 생산 억제 효과를 측정하였다.Concanavalin A was added to splenocytes of BALB / C mice, followed by treatment with white porcelain extract prepared in Example 1 to measure the effect of inhibiting the production of interleukin-4.
상세히 말하자면, 10%의 우태아 혈청이 함유된 RPMI배지가 함유된 96공 평판배양기에 생쥐의 비장세포를 400,000 세포/웰이 되도록 넣고, 콘카나발린 A를 4 ㎍/㎖ 농도로 가하여 T 임파구를 활성화시켰다. 그 다음 각 조성물을 하기 표 2의 농도대로 처리하여 36시간 후에 배양액 중으로 유리된 인터류킨-4를 ELISA 방법으로 정량하였다. 이때 콘카나발린 A만을 처리하고 조성물을 처리하지 않은 군을 대조군으로 하여 상기 수학식 1에 따라 인터류킨-4 생산 억제율을 계산하여 그 결과를 표 2에 나타내었다.Specifically, in a 96-well plate culture medium containing 10% fetal bovine serum RPMI medium, mouse spleen cells were added to 400,000 cells / well, and concanavalin A was added at a concentration of 4 μg / ml to obtain T lymphocytes. Activated. Each composition was then treated to the concentrations in Table 2 below to quantify interleukin-4 liberated into culture after 36 hours by ELISA method. At this time, using only the concanavalin A and not treated with the composition as a control group to calculate the interleukin-4 production inhibition rate according to Equation 1 shown in Table 2 the results.
상기 표 2에 나타난 바와 같이, 본 발명의 백자인 추출물은 각각 0.001%의 낮은 농도에서 활성화된 T 임파구에 의한 인터류킨-4의 생산을 억제하는 효과를 갖고 있음을 알 수 있었다.
As shown in Table 2, the white porcelain extract of the present invention was found to have the effect of inhibiting the production of interleukin-4 by activated T lymphocytes at low concentrations of 0.001%, respectively.
<< 시험예Test Example 3> T 3> T 임파구의Lymphocyte 분열증식 억제 효과 Schizoproliferation Inhibitory Effect
BALB/C 생쥐의 비장세포에 콘카나발린 A를 가한 다음, 상기 실시예 1에서 제조된 백자인 추출물을 각각 처리하여 T 임파구의 분열증식 억제 효과를 측정하였다.Concanavalin A was added to splenocytes of BALB / C mice, and the white porcelain extract prepared in Example 1 was treated, respectively, to measure the effect of inhibiting the proliferation of T lymphocytes.
상세히 말하자면, 10%의 우태아 혈청이 함유된 RPMI배지가 함유된 96공 평판배양기에 생쥐의 비장세포를 200,000 세포/웰이 되도록 넣고, 콘카나발린 A를 2 ㎍/㎖ 농도로 가하여 T 임파구를 활성화시켰다. 그 다음 각 조성물을 하기 표 3의 농도대로 처리하여 72시간 동안 배양한 후, BrdU를 5μM 농도로 가하여 12시간 추가로 배양하였다. 분열증식하는 T 임파구에 편입된 BrdU를 ELISA 방법으로 정량하였다. 이때 콘카나발린 A만을 처리하고 조성물을 처리하지 않은 군을 대조군으로 하여 상기 수학식 1에 따라 T 임파구의 분열증식 억제율을 계산하여 그 결과를 표 3에 나타내었다.Specifically, in a 96-well plate culture medium containing 10% fetal bovine serum RPMI medium, mouse spleen cells were added to 200,000 cells / well, and Concanavalin A was added at a concentration of 2 μg / ml to obtain T lymphocytes. Activated. Then, each composition was treated at the concentration of Table 3 below, followed by incubation for 72 hours, followed by further incubation for 12 hours by adding BrdU at a concentration of 5 μM. BrdU incorporated into proliferating T lymphocytes was quantified by ELISA method. At this time, using only the concanavalin A treatment and not treated with the composition as a control group according to the above formula 1 calculated the inhibition rate of division of T lymphocytes and the results are shown in Table 3.
상기 표 3에 나타난 바와 같이, 본 발명의 백자인 추출물은 각각 0.001%의 낮은 농도에서 활성화된 T 임파구의 분열증식을 억제하는 효과를 갖고 있음을 알 수 있었다.
As shown in Table 3, the white porcelain extract of the present invention was found to have an effect of inhibiting the proliferation of activated T lymphocytes at low concentrations of 0.001%, respectively.
<< 시험예Test Example 4> 4> HaCaTHaCaT 에 대한 세포 독성 측정Cytotoxicity measurement
인간 각질형성 세포주인 HaCaT 세포에 상기 실시예 1에서 제조된 백자인 추출물을 처리하여 각 조성물의 세포독성을 측정하였다.HaCaT cells, which are human keratinocyte cell lines, were treated with the white porcelain extract prepared in Example 1 to determine the cytotoxicity of each composition.
상세히 말하자면, 10%의 우태아 혈청이 함유된 DMEM 배지가 함유된 96공 평판배양기에 HaCaT 세포를 5000 세포/웰로 분주하고 세포가 부착되도록 24시간 동안 배양하였다. 여기에 각 조성물을 하기 표 4의 농도대로 처리하여 24시간 동안 배양한 다음, 50 ㎕/웰의 테트라졸리움 염색약을 가하여 4시간 동안 추가 배양하였다. 살아 있는 세포에 의해 생성된 포마잔을 150 ㎕/웰의 디메틸설폭시드 (dimethyl sulfoxide)에 용해시켜 570nm에서 흡광도를 측정함으로써 정량하였다. 용해된 포마잔에 의한 흡광도는 살아 있는 세포 수에 비례한다. 이때 조성물을 처리하지 않은 군을 대조군으로 하여 상기 수학식 1에 따라 HaCaT 세포 활성 억제율을 계산하여 그 결과를 표 4에 나타내었다.Specifically, HaCaT cells were dispensed at 5000 cells / well in a 96-well plate incubator containing DMEM medium containing 10% fetal calf serum and incubated for 24 hours to allow cell attachment. Each composition was treated in the concentration of Table 4 below for 24 hours, and then 50 μl / well of tetrazolium dye was added and further cultured for 4 hours. Formazan produced by living cells was quantified by dissolving in 150 μl / well of dimethyl sulfoxide and measuring the absorbance at 570 nm. Absorbance by lysed formazan is proportional to the number of living cells. In this case, using the group not treated with the composition as a control group according to Equation 1 to calculate the inhibition rate of HaCaT cell activity is shown in Table 4 the results.
<< 시험예Test Example 5> 인간 섬유아세포에 대한 세포 독성 측정 5> Cytotoxicity measurement on human fibroblasts
인간의 섬유아세포에 상기 실시예 1에서 제조된 백자인 추출물을 처리하여 각 조성물의 세포독성을 측정하였다.Human fibroblasts were treated with white porcelain extract prepared in Example 1 to determine the cytotoxicity of each composition.
상세히 말하자면, 10%의 우태아 혈청이 함유된 DMEM 배지가 함유된 96공 평판배양기에 섬유아세포를 5000 세포/웰로 분주하고 세포가 부착되도록 24시간 동안 배양하였다. 여기에 각 조성물을 하기 표 5의 농도대로 처리하여 24시간 동안 배양한 다음, 50 ㎕/웰의 테트라졸리움 염색약을 가하여 4시간 동안 추가 배양하였다. 살아 있는 세포에 의해 생성된 포마잔을 150 ㎕/웰의 디메틸설폭시드에 용해시켜 570nm에서 흡광도를 측정함으로써 정량하였다. 이때 조성물을 처리하지 않은 군을 대조군으로 하여 상기 수학식 1에 따라 섬유아세포 활성 억제율을 계산하여 그 결과를 표 5에 나타내었다.Specifically, fibroblasts were dispensed at 5000 cells / well in a 96-well plate incubator containing DMEM medium containing 10% fetal bovine serum and incubated for 24 hours to allow cell attachment. Each composition was treated in the concentration of Table 5 below for 24 hours, and then 50 μl / well of tetrazolium dye was added and further cultured for 4 hours. Formazan produced by living cells was quantified by dissolving in 150 μl / well of dimethylsulfoxide and measuring the absorbance at 570 nm. At this time, the fibroblast activity inhibition rate was calculated according to Equation 1 using the group not treated with the composition, and the results are shown in Table 5 below.
<< 시험예Test Example 6> 생쥐 6> mice 비장세포에On splenocytes 대한 세포 독성 측정 Cytotoxicity Measurements for
BALB/C 생쥐의 비장세포에 상기 실시예 1에서 제조된 백자인 추출물을 처리하여 각 조성물의 세포독성을 측정하였다.The splenocytes of BALB / C mice were treated with white porcelain extract prepared in Example 1 to determine the cytotoxicity of each composition.
상세히 말하자면, 10%의 우태아 혈청이 함유된 RPMI배지가 함유된 96공 평판배양기에 생쥐의 비장세포를 500,000 세포/웰이 되도록 분주하고, 여기에 각 조성물을 하기 표 6의 농도대로 처리하여 24시간 동안 배양한 다음, 50 ㎕/웰의 테트라졸리움 염색약을 가하여 4시간 동안 추가 배양하였다. 살아 있는 세포에 의해 생성된 포마잔을 150 ㎕/웰의 디메틸설폭시드에 용해시켜 570nm에서 흡광도를 측정함으로써 정량하였다. 이때 조성물을 처리하지 않은 군을 대조군으로 하여 상기 수학식 1에 따라 생쥐 비장세포 활성 억제율을 계산하여 그 결과를 표 6에 나타내었다.Specifically, in a 96-well plate culture medium containing 10% fetal bovine serum RPMI medium, the spleen cells of the mice were dispensed to 500,000 cells / well, and each composition was treated according to the concentration of Table 6 below. After incubation for an hour, 50 μl / well of tetrazolium dye was added and further incubated for 4 hours. Formazan produced by living cells was quantified by dissolving in 150 μl / well of dimethylsulfoxide and measuring the absorbance at 570 nm. At this time, the control group was treated with the composition as a control group according to the formula 1 to calculate the mouse splenocyte activity inhibition rate is shown in Table 6 the results.
상기 표 1, 표 2, 및 표 3에 제시된 결과들로부터 본 발명의 백자인 추출물은 인터류킨-2, 인터류킨-4, T임파구 분열증식과 같은T 임파구 매개성 면역반응을 효과적으로 억제한다는 것을 알 수 있었다. 이로써 본 발명의 백자인 추출물은 과도하게 활성화된 T임파구 매개성 면역반응에 관련된 아토피성 피부염, 접촉성 피부염, 건선과 같은 질환의 병증 개선 또는 예방에 있어 우수한 효과가 기대된다.From the results presented in Table 1, Table 2, and Table 3, it was found that the white porcelain extract of the present invention effectively inhibits T lymphocyte-mediated immune responses such as interleukin-2, interleukin-4, and T lymphocyte division. Thus, the white porcelain extract of the present invention is expected to have an excellent effect in improving or preventing the symptoms of diseases such as atopic dermatitis, contact dermatitis, and psoriasis related to excessively activated T lymphocyte mediated immune responses.
또한 상기 표 4, 표5, 및 표6 에서 보는 바와 같이, 본 발명의 백자인 추출물은 인간 각질형성 세포주 HaCaT 세포, 인간 섬유아세포, 생쥐 비장세포에 대해서 24시간 동안 특기할만한 독성을 나타내지 않았다. 따라서 본 발명의 백자인 추출물에 의한 T 임파구 매개성 면역반응의 억제 효과는 상기 추출물의 직접적인 독성에 의해 일어난 것이 아님을 알 수 있다. 나아가 상기 추출물은 피부 외용시 직접적인 영향을 받게 되는 각질형성 세포, 섬유아세포, 면역세포에 대해 매우 안전한 물질이라는 것을 알 수 있다.
In addition, as shown in Table 4, Table 5, and Table 6, the white porcelain extract of the present invention did not show a noticeable toxicity for human keratinocyte cell lines HaCaT cells, human fibroblasts, mouse spleen cells for 24 hours. Therefore, it can be seen that the inhibitory effect of the T lymphocyte-mediated immune response by the white porcelain extract of the present invention is not caused by the direct toxicity of the extract. Furthermore, it can be seen that the extract is a very safe substance for keratinocytes, fibroblasts, and immune cells that are directly affected by external skin application.
<< 실시예Example 2 및 2 and 비교예Comparative example > > 피부외용제(크림)의Of skin external preparation (cream) 제조 Produce
본 발명의 조성물에 의한 조성물을 외용제로 사용하기 위하여, 실시예 1의 백자인 추출물을 함유하는 조성물을 하기 표 7에 명시된 조성으로 크림을 제조하였다. 비교를 위하여, 상기 백자인 추출물을 함유하지 않은 크림 제형을 비교예로 하였다.In order to use the composition according to the composition of the present invention as an external preparation, a cream containing the white porcelain extract of Example 1 was prepared with the composition shown in Table 7 below. For comparison, a cream formulation containing no white porcelain extract was used as a comparative example.
<< 시험예Test Example 7> 인체에서 아토피 증상 개선 시험 7> Atopic symptoms improvement test in human body
본 발명의 조성물에 의한 아토피 증상 개선 효과를 확인하기 위하여, 상기 비교예 및 실시예 2에서 제조된 크림을 패널들에게 적용하여 아토피성 피부염 개선정도를 평가하였다.In order to confirm the effect of improving atopic symptoms by the composition of the present invention, the cream prepared in Comparative Examples and Example 2 was applied to the panels to evaluate the degree of atopic dermatitis improvement.
비슷한 정도의 증상을 나타내는 아토피성 피부염 증상이 있다고 생각하는 패널 20명에 대하여, 각 조 10명씩 2개조로 나누어, 온도 24~26℃, 습도 75% 조건에서 하기 표 7의 각 조성물을 매일 2회씩 12주간 안면에 도포하게 하였다. 시험을 종료한 시점에 시험 대상자들로 하여금 설문지를 작성하게 하여 주관적인 효능 평가를 실시하였다. 설문에서는 아토피성 피부염의 증상을 “소양감”, “건조함”, “각질 발생”, “비듬”, “홍반”, “부어오름”, “피부균열”, “진물과 습진” 및 “태선화본”으로 나누고, 상기 증상이 있는 경우 각각의 증상에 대하여 개선 정도를 평가한 후 이를 평균하여 아토피 증상 개선효과를 개인별로 평가하였다.For 20 panelists who had symptoms of atopic dermatitis showing similar symptoms, each group of 10 persons was divided into two groups, and each composition of Table 7 below twice daily at a temperature of 24 to 26 ° C and a humidity of 75%. It was applied to the face for 12 weeks. At the end of the study, subjects were asked to complete a questionnaire and subjective efficacy evaluations were conducted. The questionnaire included symptoms of atopic dermatitis such as “pruritus”, “dryness”, “keratogenesis”, “dandruff”, “erythema”, “swelling”, “skin cracking”, “truth and eczema”, and “chorus” In the case of the above symptoms, the degree of improvement for each symptom was evaluated and averaged to evaluate the effect of improving atopy symptoms for each individual.
그 결과를 표 8에 나타내었다.The results are shown in Table 8.
상기 표 8로부터, 본 발명의 백자인 추출물을 함유하는 조성물을 도포한 경우 아토피성 피부염 증상이 개선됨을 확인할 수 있었다. 또한, 어느 경우에도 조성물에 의한 과민반응이나 부작용은 나타나지 않았다.
From Table 8, it was confirmed that atopic dermatitis symptoms improved when the composition containing the white porcelain extract of the present invention was applied. In any case, there was no hypersensitivity reaction or side effects caused by the composition.
Claims (4)
A pharmaceutical composition for improving T lymphocyte-mediated skin immune disease containing white extract as an active ingredient.
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