KR102076936B1 - Composition including thiazole or salt thereof as active ingredients for preventing or treating allergic disease or atopic dermatitis - Google Patents
Composition including thiazole or salt thereof as active ingredients for preventing or treating allergic disease or atopic dermatitis Download PDFInfo
- Publication number
- KR102076936B1 KR102076936B1 KR1020190098385A KR20190098385A KR102076936B1 KR 102076936 B1 KR102076936 B1 KR 102076936B1 KR 1020190098385 A KR1020190098385 A KR 1020190098385A KR 20190098385 A KR20190098385 A KR 20190098385A KR 102076936 B1 KR102076936 B1 KR 102076936B1
- Authority
- KR
- South Korea
- Prior art keywords
- allergic
- thiazole
- atopic dermatitis
- composition
- allergy
- Prior art date
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- 239000000203 mixture Substances 0.000 title claims abstract description 97
- FZWLAAWBMGSTSO-UHFFFAOYSA-N Thiazole Chemical compound C1=CSC=N1 FZWLAAWBMGSTSO-UHFFFAOYSA-N 0.000 title claims abstract description 79
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Images
Classifications
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/425—Thiazoles
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- A—HUMAN NECESSITIES
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- A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
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- A—HUMAN NECESSITIES
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Abstract
Description
본 발명은 티아졸(Thiazole) 또는 이의 염을 유효성분으로 포함하는 알러지성 질환 또는 아토피 피부염 예방 또는 치료용 조성물에 관한 것이다.The present invention relates to a composition for preventing or treating allergic diseases or atopic dermatitis comprising thiazole or a salt thereof as an active ingredient.
아토피란 '이상한, 비정상적인'을 뜻하는 고대그리스어 '아토피아'에서 유래되었다. 1923년 쿡(Cooke)과 코카(Coca)는 알레르기 항원에 대한 특이 면역항체 반응을 유전적으로 야기할 수 있는 경향을 '아토피'라고 처음 부르기 시작하였다. 세계적으로 꾸준히 증가하는 추세로 산업이 발달한 선진국일수록 발병률이 증가하고 있다.Atopy is derived from the ancient Greek word "topia," meaning "weird or unusual." In 1923, Cooke and Coca first called atopy a trend that could cause genetically specific immune antibody responses to allergens. As the world continues to increase, the incidence rate of industrialized countries is increasing.
아토피의 발병 원인은 아직까지 정확히 밝혀지지 않았으나 가족력, 식생활의 변화, 알레르기 항원의 침투, 피부보호막의 이상 등 한 가지 요인에 국한되지 않고 여러 인자들이 함께 작용하여 발병한다. 주로 유·소아기에 발병하며 성인기에 지속되거나 시작 될 수도 있다. 아토피의 전형적인 증상은 손, 두피, 얼굴, 목, 팔꿈치 등에 나타나나 시기별로 나타나는 양상에 차이가 있다. 유아기의 증상은 피부가 거칠어지고 건조해지며 팔다리의 바깥쪽으로 피부염이 생기며, 뺨이나 이마 등에 흔히 나타나고 손으로 긁고 나면 진물이나 딱지가 앉게 된다. 소아기의 경우는 얼굴보다는 주로 팔과 다리와 목 등의 접히는 부위에 주로 나타나고 피부가 건조해진다. 사춘기 및 성인기에는 얼굴이나 손과 같은 부위의 피부가 두껍게 변하는 증상이 나타난다.The cause of atopic dermatitis is not known yet, but it is not limited to one factor such as family history, dietary changes, infiltration of allergens, and abnormality of skin barrier. It occurs mainly in childhood and childhood and may persist or begin in adulthood. Typical symptoms of atopy appear on the hands, scalp, face, neck, and elbows, but differ in appearance. Symptoms of infancy are rough, dry skin, dermatitis on the outside of the limbs, and often appear on the cheeks or forehead. In childhood, the skin appears mainly on the folded parts of the arms, legs, and neck, rather than the face, and the skin becomes dry. In puberty and adulthood, thickening of the skin on areas such as the face and hands occurs.
아토피 약물 치료제로는 국소 스테로이드, 국소 면역조절제, 전신 스테로이드, 전신 면역억제제, 항히스타민제가 사용된다. 국소 스테로이드제는 아토피 증상이 중증인 경우 사용하며 세균이나 바이러스 감염을 관리하는 것으로 가장 기본적인 방법이다. 그러나 스테로이드제는 1950년에 도입되어 수 년 동안 사용되어 왔지만 사용횟수와 농도, 기간 등에 따른 피부의 안전성과 내성의 문제점으로 인해 장기간의 사용이 제한되고 있다. 또한 피부의 위축(skin, atrophy), 모세혈관 확장증(telangiectasia), 스테로이드성 여드름(steroid acne) 등의 피부 부작용뿐만 아니라 HPA(hypothalamic-pituitary-adrenal) 억제, 쿠싱증후군(Cushing's syndrome)과 같은 잠재적인 부작용을 일으킬 수 있기 때문에 사용 시 충분한 주의가 필요하다. Topical steroids, topical immunomodulators, systemic steroids, systemic immunosuppressants, and antihistamines are used as atopic drugs. Topical steroids are used for severe atopic symptoms and are the most basic way to manage bacterial or viral infections. However, the steroid was introduced in 1950 and has been used for many years, but its use for a long time is limited due to problems of skin safety and resistance depending on the frequency, concentration, and duration of use. In addition, skin side effects such as skin atrophy, telangiectasia, steroid acne, as well as potential hypothalamic-pituitary-adrenal (HPA) inhibition and Cushing's syndrome Use caution when using it because it can cause side effects.
국소 면역조절제 타크로리무스(tacrolimus), 피메크로리무스(pimecrolimus)는 기존의 국소 스테로이드제와 달리 장기간 사용 시에도 비교적 부작용의 가능성이 작으므로 병변 재발의 예방 목적으로 장기간에 걸쳐서 사용할 수 있다고 알려져 있어 경증의 아토피 치료와 유지 요법으로 사용하기에 적절하다. 그러나 타크로리무스는 신장기능 저하, 손떨림, 탈모 등의 부작용이 나타날 수 있으며, 피메크로리무스는 여드름, 화끈거림 뿐만 아니라 피부암, 림프종과 같은 심각한 부작용도 나타날 수 있다. 스테로이드제는 급성기의 악화 시에, 국소 면역조절제는 경증의 아토피 치료와 유지 요법으로 사용하기에 적절하나 아직까지 부작용에 대한 안전성은 확보되지 않아 대체가능한 보완제품의 필요성이 절실한 실정이다.Unlike conventional topical steroids, tacrolimus and pimecrolimus are known to be used over a long period of time for the prevention of recurrence of lesions. Suitable for use as a treatment and maintenance therapy. However, tacrolimus may have side effects such as kidney function deterioration, shaking, and hair loss, and pimecrolimus may have serious side effects such as acne and burning, as well as skin cancer and lymphoma. In the acute phase of steroids, topical immunomodulators are suitable for use in mild atopy treatment and maintenance therapy. However, safety of side effects is not yet secured, and there is an urgent need for alternative supplements.
이에 본 출원인은 부작용이 적으며 아토피 피부염 증상을 완화시키는 데 효과가 있는 소재를 개발하기 위해 노력한 결과, 티아졸(Thiazole)이 아토피 증상을 완화하고, 염증 반응을 개선시킨다는 점을 확인함으로써 본 발명을 완성하였다.Accordingly, the present inventors endeavored to develop a material that has fewer side effects and is effective in alleviating the symptoms of atopic dermatitis. As a result, the present invention was confirmed that thiazole relieves atopic symptoms and improves the inflammatory response. Completed.
본 발명의 목적은 티아졸(Thiazole) 또는 이의 약학적으로 허용 가능한 염을 유효성분으로 포함하는 알러지성 질환 또는 아토피 피부염의 예방 또는 치료용 약학적 조성물을 제공하는 것이다.An object of the present invention is to provide a pharmaceutical composition for the prevention or treatment of allergic diseases or atopic dermatitis, including thiazole or a pharmaceutically acceptable salt thereof as an active ingredient.
본 발명의 또 다른 목적은 티아졸 또는 이의 염을 유효성분으로 포함하는 알러지성 질환 또는 아토피 피부염의 예방 또는 개선용 조성물을 제공하는 것이다.Still another object of the present invention is to provide a composition for preventing or improving allergic diseases or atopic dermatitis, including thiazole or a salt thereof as an active ingredient.
그러나, 본 발명이 이루고자 하는 기술적 과제는 이상에서 언급한 과제에 제한되지 않으며, 언급되지 않은 또 다른 과제들은 아래의 기재로부터 당업자에게 명확하게 이해될 수 있을 것이다.However, the technical problem to be achieved by the present invention is not limited to the above-mentioned problem, another task that is not mentioned will be clearly understood by those skilled in the art from the following description.
본 발명은 상술한 문제점을 해결하기 위한 것으로, 티아졸(Thiazole) 또는 이의 약학적으로 허용 가능한 염을 유효성분으로 포함하는 알러지성 질환 또는 아토피 피부염의 예방 또는 치료용 약학적 조성물을 제공한다.The present invention is to solve the above problems, and provides a pharmaceutical composition for the prevention or treatment of allergic diseases or atopic dermatitis, including thiazole or a pharmaceutically acceptable salt thereof as an active ingredient.
본 발명의 일 양상에 따르면, 상기 알러지성 질환은 부종, 과민증(anaphylaxis), 알러지성 비염(allergic rhinitis), 천식(asthma), 알러지성 결막염(allergic conjunctivitis), 알러지성 피부염(allergic dermatitis), 접촉성 피부염, 두드러기, 소양증, 곤충 알러지, 식품 알러지 및 약품 알러지로 이루어진 군에서 선택될 수 있으나, 이에 한정되지 않는다.According to one aspect of the invention, the allergic disease is edema, anaphylaxis, allergic rhinitis, asthma, allergic conjunctivitis, allergic dermatitis, contact It may be selected from the group consisting of sexual dermatitis, urticaria, pruritus, insect allergy, food allergy and drug allergy, but is not limited thereto.
본 발명의 일 양상에 따르면, 상기 유효성분은 IL-4(Interleukin-4), IL-13, TNF-α(tumor necrosis factor-alpha), IL-1β, IL-6 또는 IL-8의 발현을 감소시키거나, 히스타민의 분비량을 감소시킴으로써 항알러지 효과, 아토피 피부염의 예방 또는 치료 효과를 나타낼 수 있다.According to one aspect of the invention, the active ingredient is IL-4 (Interleukin-4), IL-13, TNF-α (tumor necrosis factor-alpha), IL-1β, IL-6 or IL-8 expression Reducing or reducing the amount of histamine secretion can have an antiallergic effect, a prophylactic or therapeutic effect of atopic dermatitis.
또한, 본 발명은 티아졸 또는 이의 약학적으로 허용 가능한 염을 유효성분으로 포함하는 알러지성 질환 또는 아토피 피부염의 예방 또는 개선용 의약외품 조성물을 제공한다.The present invention also provides a quasi-drug composition for the prevention or improvement of allergic diseases or atopic dermatitis comprising thiazole or a pharmaceutically acceptable salt thereof as an active ingredient.
또한, 본 발명은 티아졸 또는 이의 화장품학적으로 허용 가능한 염을 유효성분으로 포함하는 알러지성 질환 또는 아토피 피부염의 예방 또는 개선용 화장료 조성물을 제공한다.The present invention also provides a cosmetic composition for the prevention or improvement of allergic diseases or atopic dermatitis, including thiazole or a cosmetically acceptable salt thereof as an active ingredient.
또한, 본 발명은 티아졸 또는 이의 화장품학적으로 허용 가능한 염을 유효성분으로 포함하는 알러지성 질환 또는 아토피 피부염의 예방 또는 개선용 향료 조성물을 제공한다.The present invention also provides a fragrance composition for the prevention or improvement of allergic diseases or atopic dermatitis comprising thiazole or a cosmetically acceptable salt thereof as an active ingredient.
또한, 본 발명은 티아졸 또는 이의 식품학적으로 허용 가능한 염을 유효성분으로 포함하는 알러지성 질환 또는 아토피 피부염의 예방 또는 개선용 건강기능식품 조성물을 제공한다.The present invention also provides a health functional food composition for preventing or improving allergic disease or atopic dermatitis, including thiazole or a food acceptable salt thereof as an active ingredient.
본 발명의 티아졸을 유효성분으로 포함하는 조성물은 알러지 반응으로 인한 아토피 피부염의 개선 효과가 있으며, 염증 반응을 감소시킴으로써 다양한 알러지성 질환의 예방 또는 치료용(개선용) 조성물로 사용될 수 있다.The composition containing the thiazole of the present invention as an active ingredient has an effect of improving atopic dermatitis due to an allergic reaction, and can be used as a composition for preventing or treating (alleviating) various allergic diseases by reducing an inflammatory response.
도 1은 티아졸을 처리한 비만세포(RBL-2H3 세포)에서의 히스타민의 분비량 변화를 나타내는 그래프이다(각 값은 3 개의 독립적 웰로부터 수득한 3 회의 평균 ± SEM 임; 막대 위의 글자는 P<0.05에서 통계적 유의적 차이를 나타낸 것임).
도 2는 티아졸을 처리한 비만세포에서 염증성 사이토카인 관련 분자들(IL-4, IL-13 및 TNF-α)의 발현변화를 나타내는 그래프이다(각 값은 3 개의 독립적 웰로부터 수득한 3 회의 평균 ± SEM 임; 막대 위의 글자는 P<0.05에서 통계적 유의적 차이를 나타낸 것임).
도 3은 티아졸을 처리한 각질형성세포에서 염증성 사이토카인 관련 분자들(IL-1β, IL-6 및 IL-8)의 발현변화를 나타내는 그래프이다(각 값은 3 개의 독립적 웰로부터 수득한 3 회의 평균 ± SEM 임; 막대 위의 글자는 P<0.05에서 통계적 유의적 차이를 나타낸 것임).1 is a graph showing changes in histamine secretion in thiazole-treated mast cells (RBL-2H3 cells) (each value is three mean ± SEM obtained from three independent wells; the letters on the bars are P Statistically significant difference at <0.05).
FIG. 2 is a graph showing the expression changes of inflammatory cytokine related molecules (IL-4, IL-13 and TNF-α) in thiazole-treated mast cells (each value being 3 times obtained from 3 independent wells) Mean ± SEM; letters above the bars show statistically significant difference at P <0.05).
3 is a graph showing the expression changes of inflammatory cytokine related molecules (IL-1β, IL-6 and IL-8) in thiazole-treated keratinocytes (each value is 3 obtained from three independent wells). Council mean ± SEM; letters above the bar show statistically significant differences at P <0.05).
본 발명자들은 티아졸이 아토피 증상을 완화시키며, 세포의 면역반응으로 인해 분비되는 염증성 사이토카인인 IL-4, IL-13, TNF-α, IL-1β, IL-6 또는 IL-8의 발현을 유의적으로 감소시키는 것과 히스타민의 분비량을 감소시키는 것을 확인함으로써, 본 발명을 완성하였다.The inventors have found that thiazoles alleviate atopic symptoms and express the expression of inflammatory cytokines IL-4, IL-13, TNF-α, IL-1β, IL-6 or IL-8, which are secreted by cellular immune responses. The present invention was completed by confirming a significant reduction and a decrease in the amount of histamine secretion.
이하, 본 발명을 상세히 설명한다. Hereinafter, the present invention will be described in detail.
본 발명은 티아졸(Thiazole) 또는 이의 염을 유효성분으로 포함하는 알러지성 질환 또는 아토피 피부염의 예방 또는 치료용 조성물을 제공한다.The present invention provides a composition for the prevention or treatment of allergic diseases or atopic dermatitis comprising thiazole or a salt thereof as an active ingredient.
구체적으로 상기 티아졸(Thiazole)은 헤테로고리(heterocyclic)계 화합물로서, IUPAC 명(name)은 1,3-티아졸(1,3-Thiazole)이고 티아졸(thiazole), 5H-티아졸-1-이움(5H-Thiazol-1-ium), 5H-1,3-티아졸 (5H-1,3-thiazole) 등의 이명을 가진다. 티아졸의 구조식은 C3H3NS이고 분자량은 85.12 g/mol 이며, 구조는 아래 [화학식 1]과 같다. Specifically, the thiazole is a heterocyclic compound, the IUPAC name is 1,3-thiazole, thiazole, 5H-thiazole-1 -Has the tinnitus (5H-Thiazol-1-ium), 5H-1,3-thiazole (5H-1,3-thiazole). The structural formula of thiazole is C 3 H 3 NS and the molecular weight is 85.12 g / mol, the structure is as shown in [Formula 1].
티아졸은 무색 또는 담황색의 투명한 액체이며 비린내와 비슷한 냄새를 낸다. 티아졸은 향료로써 사용 가능한 안전한 물질로 알려져 있으며, FEMA(Flavor and Extract Manufacturers'Association), FDA(Food and Drug Administration), JECFA(Joint FAO/WHO Expert Committee on Food Additives)에 의해 착향료(flavor agents) 성분으로 승인되어 있고, 산업적으로 맛과 향을 내기 위한 목적으로 이용되어져 왔다. Thiazole is a colorless or pale yellow clear liquid with a fishy odor. Thiazoles are known as safe substances that can be used as fragrances and are flavored agents by Flavor and Extract Manufacturers' Association (FEMA), Food and Drug Administration (FDA), and Joint FAO / WHO Expert Committee on Food Additives (JECFA). It is approved as an ingredient and has been used industrially for flavor and aroma.
[화학식 1][Formula 1]
본 발명의 티아졸은 상기 티아졸과 동일한 효능을 갖는 범위 내에서 티아졸 수화물, 티아졸 유도체 등을 포함할 수 있고, 이의 용매 화합물이나 입체 이성질체 또한 포함할 수 있다.The thiazole of the present invention may include thiazole hydrate, thiazole derivative, and the like within the range having the same efficacy as the thiazole, and may also include a solvent compound or stereoisomer thereof.
상기 티아졸의 수득방법은 특별히 한정되지 않으며, 상기 티아졸을 함유하고 있는 식물로부터 분리하거나, 공지된 제법을 사용하여 화학적으로 합성하거나, 시판되는 것을 사용할 수 있다.The method for obtaining the thiazole is not particularly limited, and may be isolated from the plant containing the thiazole, chemically synthesized using a known production method, or commercially available.
본 발명에서, 용어 "화장품학적으로 허용 가능한 염", "식품학적으로 허용 가능한 염", "약학적으로 허용 가능한 염" 또는 "이의 염"은 유리산(free acid)에 의해 형성된 산 부가염일 수 있다. 산 부가염은 통상의 방법, 예를 들어 화합물을 과량의 산 수용액에 용해시키고, 이 염을 수혼화성 유기 용매, 예를 들어 메탄올, 에탄올, 아세톤 또는 아세토니트릴을 사용하여 침전시켜서 제조할 수 있다. 또한, 동 몰량의 화합물 및 물 중의 산 또는 알코올(예를 들어, 글리콜 모노메틸 에테르)을 가열하고, 이어서 상기 혼합물을 증발시켜 건조시키거나, 또는 석출된 염을 흡인 여과시킬 수 있다.In the present invention, the term "cosmetic acceptable salt", "food acceptable salt", "pharmaceutically acceptable salt" or "salt thereof" may be an acid addition salt formed by free acid. have. Acid addition salts can be prepared by conventional methods, for example by dissolving a compound in an excess of aqueous acid solution and precipitating the salt using a water miscible organic solvent, such as methanol, ethanol, acetone or acetonitrile. In addition, equimolar amounts of the compound and acid or alcohol (eg, glycol monomethyl ether) in water can be heated and the mixture can then be evaporated to dryness or the precipitated salts can be suction filtered.
상기 유리산으로는 무기산 또는 유기산을 사용할 수 있다. 상기 무기산의 비제한적인 예로는 염산, 인산, 황산, 질산, 주석산 등을 사용할 수 있으며, 이들은 단독으로 사용되거나 2 종 이상을 혼합하여 사용될 수 있다. 상기 유기산의 비제한적인 예로는 메탄술폰산, p-톨루엔술폰산, 아세트산, 트리플루오로아세트산, 말레인산(maleic acid), 숙신산, 옥살산, 벤조산, 타르타르산, 푸마르산 (fumaric acid), 만데르산, 프로피온산(propionic acid), 구연산(citric acid), 젖산(lactic acid), 글리콜산(glycollic acid), 글루콘산(gluconic acid), 갈락투론산(galacturonic acid), 글루탐산, 글루타르산(glutaric acid), 글루쿠론산 (glucuronic acid), 아스파르트산, 아스코르브산, 카본산, 바닐릭산, 하이드로아이오딕산 등을 사용할 수 있다. 이들은 단독으로 사용되거나 2 종 이상을 혼합하여 사용될 수 있다.As the free acid, an inorganic acid or an organic acid may be used. Non-limiting examples of the inorganic acid may be hydrochloric acid, phosphoric acid, sulfuric acid, nitric acid, tartaric acid, and the like, which may be used alone or in combination of two or more. Non-limiting examples of the organic acid are methanesulfonic acid, p-toluenesulfonic acid, acetic acid, trifluoroacetic acid, maleic acid, succinic acid, oxalic acid, benzoic acid, tartaric acid, fumaric acid, manderic acid, propionic acid acid, citric acid, lactic acid, glycolic acid, glycolic acid, gluconic acid, galacturonic acid, glutamic acid, glutaric acid, glucuronic acid (glucuronic acid), aspartic acid, ascorbic acid, carbonic acid, vanic acid, hydroiodic acid and the like can be used. These may be used alone or in combination of two or more thereof.
또한, 상기 티아졸은 염기를 사용하여 화장품학적으로 또는 식품학적으로 허용 가능한 금속염을 만들 수 있다. 알칼리 금속 또는 알칼리 토금속 염은, 예를 들어 화합물을 과량의 알칼리 금속 수산화물 또는 알칼리 토금속 수산화물 용액 중에 용해시키고, 비용해 화합물 염을 여과한 후 여액을 증발, 건조시켜 얻을 수 있다. 상기 금속염으로는 특히 나트륨, 칼륨 또는 칼슘염을 제조하는 것이 바람직하나 이들에 제한되는 것은 아니다. 또한, 이에 대응하는 은염은 알칼리 금속 또는 알칼리 토금속 염을 적당한 은염 (예를 들어, 질산은)과 반응시켜 얻을 수 있다.In addition, the thiazole can be used to make a cosmetically or food acceptable metal salt. Alkali metal or alkaline earth metal salts can be obtained, for example, by dissolving the compound in an excess of alkali metal hydroxide or alkaline earth metal hydroxide solution, filtering the insoluble compound salt, and then evaporating and drying the filtrate. As the metal salt, it is particularly preferable to prepare sodium, potassium or calcium salts, but is not limited thereto. Corresponding silver salts can also be obtained by reacting an alkali metal or alkaline earth metal salt with a suitable silver salt (eg silver nitrate).
상기 티아졸의 염은, 달리 지시되지 않는 한, 상기 티아졸의 화합물에 존재할 수 있는 산성 또는 염기성 기의 염을 모두 포함할 수 있다. 예를 들어 상기 티아졸의 염으로는 하이드록시기의 나트륨, 칼슘 및 칼륨염 등이 포함될 수 있고, 아미노기의 기타 화장품학적으로 허용 가능한 염으로는 하드로브로마이드, 황산, 수소 황산염, 인산염, 수소 인산염, 이수소 인산염, 아세테이트, 숙시네이트, 시트레이트, 타르트레이트, 락테이트, 만델레이트, 메탄술포네이트 (메실레이트) 및 p-톨루엔술포네이트 (토실레이트)염 등을 들 수 있으며 당업계에서 알려진 염의 제조 방법을 통하여 제조될 수 있다.Salts of the thiazoles may include all salts of acidic or basic groups which may be present in the compound of the thiazoles unless otherwise indicated. For example, the salt of the thiazole may include sodium, calcium and potassium salts of the hydroxy group, and other cosmetically acceptable salts of the amino group include hardbromide, sulfuric acid, hydrogen sulphate, phosphate, and hydrogen phosphate. , Dihydrogen phosphate, acetate, succinate, citrate, tartrate, lactate, mandelate, methanesulfonate (mesylate) and p-toluenesulfonate (tosylate) salts and the like. It may be prepared through a manufacturing method.
본 발명에서 "알러지성 질환"이란 외부 항원에 대한 신체 내 면역 반응이 과도하게 나타나는 알러지(allergy) 반응에 의해 발병하는 질환을 의미하는 것으로서, 구체적으로 부종, 과민증(anaphylaxis), 알러지성 비염(allergic rhinitis), 천식(asthma), 알러지성 결막염(allergic conjunctivitis), 알러지성 피부염(allergic dermatitis), 접촉성 피부염, 두드러기, 소양증, 곤충 알러지, 식품 알러지 및 약품 알러지로 이루어진 군에서 선택되는 하나 이상의 질환일 수 있으나, 이에 한정되지 않는다.In the present invention, "allergic disease" refers to a disease caused by an allergy reaction in which the body's immune response to an external antigen is excessive, and specifically, edema, anaphylaxis, and allergic rhinitis one or more disease days selected from the group consisting of rhinitis, asthma, allergic conjunctivitis, allergic dermatitis, epidermal contact dermatitis, urticaria, pruritus, insect allergy, food allergy and drug allergy But it is not limited thereto.
본 발명에서 "아토피 피부염"은 알러지성 질환 중의 하나로서 가려움증, 피부 건조, 피부 두께 증가, 특징적인 습진과 같은 증상을 동반하는 피부 질환이다. In the present invention, "atopic dermatitis" is one of allergic diseases and is a skin disease accompanied by symptoms such as itching, dry skin, increased skin thickness, and characteristic eczema.
본 발명에 따른 알러지성 질환 또는 아토피 피부염의 예방 또는 치료용 약학적 조성물은 티아졸 또는 이의 약학적으로 허용 가능한 염을 포함하는 것이라면 그 함량을 특별히 제한하지는 않으나, 바람직하게 상기 티아졸의 용량은 0.1 μM 내지 1000 μM의 농도로 포함할 수 있으나, 이에 한정되지 않는다. 이때, 티아졸이 상기 농도 범위 미만인 경우, 바람직한 예방 또는 치료 효과를 발휘하기 어려운 문제점이 있고, 티아졸이 상기 농도 범위를 초과하는 경우, 세포독성을 포함한 독성의 우려사항이 있을 수 있다.The pharmaceutical composition for the prophylaxis or treatment of allergic diseases or atopic dermatitis according to the present invention is not particularly limited as long as it contains thiazole or a pharmaceutically acceptable salt thereof, preferably the dose of thiazole is 0.1 It may include a concentration of μM to 1000 μM, but is not limited thereto. At this time, if the thiazole is less than the concentration range, there is a problem that it is difficult to exert a desirable prophylactic or therapeutic effect, and if the thiazole exceeds the concentration range, there may be a concern of toxicity including cytotoxicity.
본 발명에 따른 알러지성 질환 또는 아토피 피부염의 예방 또는 치료용 약학 조성물은 각각 통상의 방법에 따라 산제, 과립제, 정제, 캡슐제, 현탁액, 에멀젼, 시럽, 에어로졸 등의 경구제 제형, 외용제, 좌제 및 멸균 주사용액의 형태로 제형화되어 사용할 수 있고, 제형화를 위하여 약학 조성물의 제조에 통상적으로 사용되는 적절한 담체, 부형제 또는 희석제를 포함할 수 있다.Pharmaceutical compositions for the prophylaxis or treatment of allergic diseases or atopic dermatitis according to the present invention are powder, granules, tablets, capsules, suspensions, emulsions, syrups, aerosols, etc. It can be formulated and used in the form of sterile injectable solutions and can include suitable carriers, excipients or diluents commonly used in the manufacture of pharmaceutical compositions for formulation.
상기 담체 또는, 부형제 또는 희석제로는 락토즈, 덱스트로즈, 수크로오스, 솔비톨, 만니톨, 자일리톨, 에리스리톨, 말티톨, 전분, 아카시아 고무, 알지네이트, 젤라틴, 칼슘 포스페이트, 칼슘 실리게이트, 셀룰로즈, 메틸 셀룰로즈, 미정질 셀룰로즈, 폴리비닐 피롤리돈, 물, 메틸히드록시벤조에이트, 프로필히드록시벤조에이트, 탈크, 마그네슘 스테아레이트 및 광물유 등을 포함한 다양한 화합물 혹은 혼합물을 들 수 있다.The carrier or excipient or diluent may be lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, acacia rubber, alginate, gelatin, calcium phosphate, calcium silicate, cellulose, methyl cellulose, undetermined. And various compounds or mixtures including vaginal cellulose, polyvinyl pyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate, mineral oil and the like.
제제화할 경우에는 보통 사용하는 충진제, 중량제, 결합제, 습윤제, 붕해제, 계면활성제 등의 희석제 또는 부형제를 사용하여 제조할 수 있다.In the case of formulation, it may be prepared by using diluents or excipients such as fillers, weights, binders, wetting agents, disintegrating agents, and surfactants which are commonly used.
경구 투여를 위한 고형제제는 상기 티아졸에 적어도 하나 이상의 부형제 예를 들면, 전분, 칼슘보네이트, 수크로스 또는 락토오스, 젤라틴 등을 섞어 제조할 수 있다. 또한 단순한 부형제 이외에 마그네슘 스테아레이트, 탈크 같은 윤활제들도 사용할 수 있다.Solid preparations for oral administration may be prepared by mixing at least one excipient such as starch, calcium carbonate, sucrose or lactose, gelatin and the like with the thiazole. In addition to simple excipients, lubricants such as magnesium stearate and talc may also be used.
경구를 위한 액상 제제로는 현탁액, 내용액제, 유제, 시럽제 등이 해당되는데 흔히 사용하는 단순 희석제인 물, 리퀴드 파라핀 이외에 여러 가지 부형제, 예를 들면 습윤제, 감미제, 방향제, 보존제 등을 포함할 수 있다.Oral liquid preparations include suspensions, solvents, emulsions, and syrups, and may include various excipients, such as wetting agents, sweeteners, fragrances, preservatives, etc., in addition to commonly used simple diluents such as water and liquid paraffin. .
비경구 투여를 위한 제제에는 멸균된 수용액, 비수용성제, 현탁제, 유제, 동결건조 제제, 좌제가 포함된다. 비수성용제, 현탁제로는 프로필렌글리콜, 폴리에틸렌 글리콜, 올리브 오일과 같은 식물성 기름, 에틸올레이트와 같은 주사 가능한 에스테르 등을 사용할 수 있다. 좌제의 기제로는 위텝솔(witepsol), 마크로골, 트윈(tween) 61, 카카오지, 라우린지, 글리세롤젤라틴 등을 사용할 수 있다.Formulations for parenteral administration include sterile aqueous solutions, non-aqueous solutions, suspensions, emulsions, lyophilized preparations, suppositories. As the non-aqueous solvent and suspending agent, propylene glycol, polyethylene glycol, vegetable oil such as olive oil, injectable ester such as ethyl oleate and the like can be used. As a base of suppositories, witepsol, macrogol, tween 61, cacao butter, laurin butter, glycerol gelatin and the like can be used.
본 발명에 따른 알러지성 질환 또는 아토피 피부염의 예방 또는 치료용 약학 조성물의 바람직한 투여량은 환자의 상태, 체중, 질병의 정도, 약물형태, 투여경로 및 기간에 따라 다르지만, 당업자에 의해 적절하게 선택될 수 있다. 그러나, 바람직한 효과를 위해서는 1일 0.0001 내지 2,000 mg/kg으로, 바람직하게는 0.001 내지 2,000 mg/kg으로 투여할 수 있다. 투여는 하루에 한 번 투여할 수도 있고, 수회 나누어서 투여할 수도 있다. 다만, 상기 투여량에 의해서 본 발명의 범위를 한정하는 것은 아니다.The preferred dosage of the pharmaceutical composition for the prophylaxis or treatment of allergic disease or atopic dermatitis according to the present invention depends on the patient's condition, body weight, degree of disease, drug form, route of administration and duration, but may be appropriately selected by those skilled in the art. Can be. However, for the desired effect, it may be administered at 0.0001 to 2,000 mg / kg, preferably at 0.001 to 2,000 mg / kg. Administration may be administered once a day or may be divided several times. However, the scope of the present invention is not limited by the above dosage.
본 발명에 따른 알러지성 질환 또는 아토피 피부염의 예방 또는 치료용 약학 조성물은 쥐, 생쥐, 가축, 인간 등의 포유 동물에 다양한 경로로 투여할 수 있다. 투여의 모든 방식은 예를 들면, 경구, 직장 또는 정맥, 근육, 피하, 자궁 내 경막 또는 뇌혈관내(intracerebroventricular) 주사에 의해서 투여할 수 있다.Pharmaceutical compositions for the prevention or treatment of allergic diseases or atopic dermatitis according to the present invention can be administered to mammals such as rats, mice, livestock, humans by various routes. All modes of administration can be administered, for example, by oral, rectal or intravenous, intramuscular, subcutaneous, intrauterine dural or intracerebroventricular injection.
본 발명에 따른 유효성분을 포함하는 조성물은 면역 반응으로 인해 과도하게 분비되는 IL-4, IL-13, TNF-α, IL-1β, IL-6 또는 IL-8의 발현을 감소시키거나 히스타민의 분비량을 감소시킴으로써 알러지 질환 또는 아토피 피부염 증상을 개선하고 예방할 수 있다.The composition comprising the active ingredient according to the present invention reduces the expression of IL-4, IL-13, TNF-α, IL-1β, IL-6 or IL-8 that is excessively secreted due to an immune response, Reducing the amount of secretion can improve and prevent symptoms of allergic disease or atopic dermatitis.
대표적인 가려움증 매개체인 히스타민은 1927년 Lewis에 의해서 염증성 피부질환에서 가려움증을 일으킨다고 제안되었다. 피부의 히스타민의 주요 공급원은 비만세포로 합성 및 저장된 히스타민이 자극에 반응하여 분비된다. 분비된 히스타민은 각질 세포에 존재하는 히스타민 수용체를 통하여 가려움증 외에도 혈관에 대한 직접적인 작용과 감각 신경에서 신경펩티드(neuropeptide)의 방출로 인해 홍반, 통증, 혈관 확장 및 부종을 유발한다.Histamine, a representative itch carrier, was proposed by Lewis in 1927 to cause itching in inflammatory skin diseases. The major source of histamine in the skin is mast cells, where histamine synthesized and stored is secreted in response to stimuli. Secreted histamine causes erythema, pain, vasodilation and swelling due to its direct action on blood vessels and the release of neuropeptides from sensory nerves in addition to itching through histamine receptors present in keratinocytes.
본 발명의 일 실시예에서는, 티아졸 처리 결과, 대표적인 가려움증 매개체인 히스타민의 분비량이 현저히 감소되는 것을 확인함으로써 티아졸이 알러지 질환 또는 아토피 피부염 증상을 개선하고 예방할 수 있음을 확인하였다(도 1).In one embodiment of the present invention, as a result of the thiazole treatment, it was confirmed that the secretion amount of histamine, which is a representative itch mediator, was significantly reduced, and it was confirmed that thiazole can improve and prevent symptoms of allergic disease or atopic dermatitis (FIG. 1).
또한 본 발명의 일 실시예에서는, 티아졸 처리 결과, 세포의 면역반응으로 분비되는 염증성 사이토카인인 IL-4, IL-13, TNF-α, IL-1β, IL-6 및 IL-8의 발현이 현저히 감소한 것을 확인함으로써 티아졸이 과도한 면역 반응을 억제하고 염증을 치료할 수 있음을 할 수 있었다(도 2, 도 3).In addition, in one embodiment of the present invention, the expression of inflammatory cytokines IL-4, IL-13, TNF-α, IL-1β, IL-6 and IL-8 secreted by the cell's immune response as a result of thiazole treatment By confirming this marked decrease, it was possible that the thiazoles can suppress excessive immune responses and cure inflammation (FIGS. 2 and 3).
또한, 본 발명은 티아졸(Thiazole) 또는 이의 염을 유효성분으로 포함하는 알러지성 질환 또는 아토피 피부염의 예방 또는 개선용 조성물을 제공한다.The present invention also provides a composition for the prevention or improvement of allergic diseases or atopic dermatitis, including thiazole or a salt thereof as an active ingredient.
상기 티아졸의 구체적인 내용은 전술한 바와 같다.Specific contents of the thiazole are as described above.
본 발명의 알러지성 질환 또는 아토피 피부염의 예방 또는 개선용 조성물은 건강기능식품 조성물, 화장료 조성물, 향료 조성물 또는 의약외품 조성물일 수 있다.The composition for the prevention or improvement of allergic diseases or atopic dermatitis of the present invention may be a dietary supplement, cosmetic composition, fragrance composition or quasi-drug composition.
본 발명에서 용어 "건강기능식품"은 인체에 유용한 기능성을 가진 원료나 성분을 사용하여 정제, 캅셀, 분말, 과립, 액상 및 환 등의 형태로 제조 및 가공한 식품을 말한다. 여기서 '기능성'이라 함은 인체의 구조 및 기능에 대하여 영양소를 조절하거나 생리학적 작용 등과 같은 보건용도에 유용한 효과를 얻는 것을 의미한다. 본 발명의 건강기능식품은 당 업계에서 통상적으로 사용되는 방법에 의하여 제조가능하며, 상기 제조시에는 당 업계에서 통상적으로 첨가하는 원료 및 성분을 첨가하여 제조할 수 있다. 또한 상기 건강기능식품의 제형 또한 건강기능식품으로 인정되는 제형이면 제한 없이 제조될 수 있다. 본 발명의 건강기능식품 조성물은 일반 약품과는 달리 식품을 원료로 하여 약품의 장기 복용 시 발생할 수 있는 부작용 등이 없는 장점이 있고, 휴대성이 뛰어나, 항알러지 효과 또는 아토피 피부염 증상 완화 효과를 증진시키기 위한 보조제로 섭취가 가능하다.In the present invention, the term "health functional food" refers to a food prepared and processed in the form of tablets, capsules, powders, granules, liquids and pills using raw materials or ingredients having useful functions for the human body. Here, 'functional' means to obtain a useful effect for health purposes such as nutrient control or physiological action on the structure and function of the human body. The health functional food of the present invention can be prepared by a method commonly used in the art, and the preparation can be prepared by adding raw materials and ingredients commonly added in the art. In addition, the formulation of the health functional food may also be prepared without limitation as long as the formulation is recognized as a health functional food. Unlike the general medicine, the health functional food composition of the present invention has the advantage that there is no side effect that may occur when taking a long-term use of the drug, as a raw material, and has excellent portability, and promotes an antiallergic effect or atopic dermatitis symptomatic effect. It can be taken as a supplement.
본 발명에 따른 알러지성 질환 또는 아토피 피부염의 예방 또는 개선용 건강기능식품에 있어서, 상기 티아졸을 건강기능식품의 첨가물로 사용하는 경우 이를 그대로 첨가하거나 다른 식품 또는 식품성분과 함께 사용할 수 있고, 통상적인 방법에 따라 적절하게 사용할 수 있다. 유효 성분의 혼합양은 예방, 건강 또는 치료 등의 각 사용 목적에 따라 적합하게 결정할 수 있다.In the dietary supplement for the prevention or improvement of allergic diseases or atopic dermatitis according to the present invention, when the thiazole is used as an additive of the dietary supplement, it may be added as it is or used with other foods or food ingredients, and It can use suitably according to phosphorus method. The mixed amount of the active ingredient can be appropriately determined depending on the purpose of use, such as prevention, health or treatment.
건강기능식품의 제형은 산제, 과립제, 환, 정제, 캡슐제의 형태뿐만 아니라 일반 식품 또는 음료의 형태 어느 것이나 가능하다.Formulations of dietary supplements may be in the form of powders, granules, pills, tablets, capsules, as well as in the form of general foods or beverages.
상기 식품의 종류에는 특별히 제한은 없고, 상기 물질을 첨가할 수 있는 식품의 예로는 육류, 소세지, 빵, 쵸콜렛, 캔디류, 스넥류, 과자류, 피자, 라면, 기타 면류, 껌류, 아이스크림류를 포함한 낙농제품, 각종 스프, 음료수, 차, 드링크제, 알콜 음료 및 비타민 복합제 등이 있으며, 통상적인 의미에서의 식품을 모두 포함할 수 있다.There is no restriction | limiting in particular in the kind of said food, The foodstuff which can add the said substance is a dairy product including meat, sausage, bread, chocolate, candy, snacks, confectionery, pizza, ramen, other noodles, gum, ice cream, etc. , Various soups, beverages, tea, drinks, alcoholic beverages and vitamin complexes, etc., may include all of the food in the usual sense.
일반적으로, 식품 또는 음료의 제조시에 상기 티아졸은 원료 100 중량부에 대하여 15 중량부 이하, 바람직하게는 10 중량부 이하의 양으로 첨가할 수 있다. 그러나, 건강 및 위생을 목적으로 하거나 또는 건강 조절을 목적으로 하는 장기간의 섭취의 경우에는 상기 양은 상기 범위 이하일 수 있으며, 또한 본 발명은 천연물로부터의 분획물을 이용하는 점에서 안전성 면에서 문제가 없으므로 상기 범위 이상의 양으로도 사용할 수 있다.Generally, the thiazole may be added in an amount of 15 parts by weight or less, preferably 10 parts by weight or less, based on 100 parts by weight of the raw material in the manufacture of food or beverage. However, in the case of long-term intake for health and hygiene or for health control, the amount may be below the above range, and the present invention has no problem in terms of safety in terms of using fractions from natural products. The above amount can also be used.
본 발명에 따른 기능성식품 중 음료는 통상의 음료와 같이 여러 가지 향미제 또는 천연 탄수화물 등을 추가 성분으로 함유할 수 있다. 상술한 천연 탄수화물은 포도당, 과당과 같은 모노사카라이드, 말토스, 슈크로스와 같은 디사카라이드 및 덱스트린, 사이클로덱스트린과 같은 폴리사카라이드, 자일리톨, 소르비톨, 에리트리톨 등의 당알콜일 수 있다. 감미제로서는 타우마틴, 스테비아 추출물과 같은 천연 감미제나, 사카린, 아스파르탐과 같은 합성 감미제 등을 사용할 수 있다. 상기 천연 탄수화물의 비율은 본 발명에 따른 음료 100 mL당 약 0.01 ~ 0.04 g, 바람직하게는 약 0.02 ~ 0.03 g일 수 있다.In the functional food according to the present invention, the beverage may contain various flavors or natural carbohydrates and the like as an additional component as a general beverage. The natural carbohydrates described above may be glucose, monosaccharides such as fructose, maltose, disaccharides such as sucrose and polysaccharides such as dextrin, cyclodextrin, sugar alcohols such as xylitol, sorbitol, erythritol. As the sweetener, natural sweeteners such as tautin and stevia extract, synthetic sweeteners such as saccharin and aspartame, and the like can be used. The ratio of the natural carbohydrate may be about 0.01 to 0.04 g, preferably about 0.02 to 0.03 g per 100 mL of the beverage according to the present invention.
상기 외에 본 발명에 따른 알러지성 질환 또는 아토피 피부염의 예방 또는 개선용 건강기능식품은 여러 가지 영양제, 비타민, 전해질, 풍미제, 착색제, 펙트산 및 그의 염, 알긴산 및 그의 염, 유기산, 보호성 콜로이드 증점제, pH 조절제, 안정화제, 방부제, 글리세린, 알콜, 탄산음료에 사용되는 탄산화제를 함유할 수 있다. 그 밖에 본 발명의 알러지성 질환 또는 아토피 피부염의 예방 또는 개선용 건강기능식품 조성물은 천연 과일쥬스, 과일쥬스 음료 및 야채 음료의 제조를 위한 과육을 함유할 수 있다. 이러한 성분은 독립적으로 또는 혼합하여 사용할 수 있다. 이러한 첨가제의 비율은 제한되지 않으나 본 발명의 기능성식품 100 중량부 대비 0.01 ~ 0.1 중량부의 범위에서 선택되는 것이 일반적이다.In addition to the above, the health functional food for preventing or improving allergic diseases or atopic dermatitis according to the present invention is various nutrients, vitamins, electrolytes, flavoring agents, coloring agents, pectic acid and salts thereof, alginic acid and salts thereof, organic acids, protective colloids. And thickening agents, pH adjusting agents, stabilizers, preservatives, glycerin, alcohols, carbonation agents used in carbonated beverages. In addition, the nutraceutical composition for the prevention or improvement of allergic diseases or atopic dermatitis of the present invention may contain a pulp for the production of natural fruit juice, fruit juice beverage and vegetable beverage. These components can be used independently or in combination. The ratio of such additives is not limited, but is generally selected from 0.01 to 0.1 parts by weight relative to 100 parts by weight of the functional food of the present invention.
본 발명에서 사용되는 용어, "화장료 조성물"은 상기 화합물을 포함하는 조성물로서 그 제형은 어떠한 형태라도 가능하다. 이러한 제형의 예를 들면 상기 조성물을 이용하여 제조된 화장료는 영양크림, 아이크림, 마사지크림, 클렌징 크림과 같은 크림류, 팩류, 영양로션과 같은 로션류, 에센스류, 유연화장수, 영양화장수와 같은 화장수류, 파우더류, 파운데이션류 및 메이크업 베이스류 등이고, 본 발명의 목적을 달성하기 위하여 이러한 제형 중 어떠한 형태로도 제조되어 상용화될 수 있으며, 상기 예들에 한정되지 않는다. 또한, 본 발명에 따른 화장료 조성물에는 통상의 화장료 제조 방법으로 제형화할 수 있다. 구체적으로 본 발명의 화장료는 스킨로션, 스킨 소프너, 스킨토너, 아스트린젠트, 로션, 밀크로션, 모이스처 로션, 영양로션, 맛사지 크림, 영양크림, 모이스처 크림, 핸드크림, 에센스, 팩, 마스크팩, 마스크시트, 비누, 샴푸, 클렌징폼, 클렌징로션, 클렌징크림, 바디로션, 바디클렌저, 유액, 프레스파우더, 루스파우더 및 아이섀도로 구성된 그룹에서 선택된 어느 하나의 제형을 가지는 것일 수 있다.As used herein, the term "cosmetic composition" is a composition comprising the compound, the formulation may be in any form. For example, the cosmetics prepared using the composition may be a nourishing cream, eye cream, massage cream, creams such as cleansing creams, packs, lotions such as nutrient lotions, essences, soft cosmetics, nourishing cosmetics. , Powders, foundations, makeup bases, and the like, and may be prepared and commercialized in any of these formulations to achieve the object of the present invention, and are not limited to the above examples. In addition, the cosmetic composition according to the present invention can be formulated by a conventional cosmetic preparation method. Specifically, the cosmetics of the present invention include skin lotion, skin softener, skin toner, astringent, lotion, milk lotion, moisturizing lotion, nutrition lotion, massage cream, nutrition cream, moisture cream, hand cream, essence, pack, mask pack, mask sheet It may be one having a formulation selected from the group consisting of soap, shampoo, cleansing foam, cleansing lotion, cleansing cream, body lotion, body cleanser, emulsion, press powder, loose powder and eye shadow.
본 발명의 화장료 조성물은 티아졸 또는 이의 염에 더하여 부형제, 담체 등 기타 첨가제를 포함할 수 있으며, 일반 피부 화장료에 배합되는 보통의 성분을 필요한 만큼 적용 배합하는 것이 가능하다.The cosmetic composition of the present invention may include other additives such as excipients, carriers, etc. in addition to thiazole or salts thereof, and it is possible to apply and blend the usual ingredients necessary for general skin cosmetics as necessary.
구체적으로, 본 발명의 화장료 조성물은 경피 침투 강화제를 추가로 포함할 수 있다. 본 발명에서 사용되는 용어, 경피 침투 강화제란 피부의 혈관세포 내로 원하는 성분이 높은 흡수율로 침투할 수 있게 해주는 조성물이다. 바람직하게는 레시틴 화장품에 사용되는 다른 인지질 성분, 리포좀 성분 등이 포함되지만 이에 국한되지는 않는다.Specifically, the cosmetic composition of the present invention may further include a transdermal penetration enhancer. As used herein, the term transdermal penetration enhancer is a composition that allows a desired component to penetrate into blood vessel cells of the skin at a high absorption rate. Preferably other phospholipid components, liposome components and the like used in lecithin cosmetics are included, but are not limited thereto.
또한, 유상 성분으로서 주로 사용될 수 있는 오일로는 식물성 오일, 광물성 오일, 실리콘유 및 합성유 중에서 선택된 하나 이상을 사용할 수 있다. 보다 구체적으로, 미네랄오일, 사이크로메치콘, 스쿠알란, 옥틸도데실 미리스테이트, 올리브오일, 비티스 비니페라 씨드 오일, 마카다미아너트오일, 글리세릴옥타노에이트, 캐스터오일, 에칠헥실 이소노나노에이트, 디메치콘, 사이크로펜타실록산 및 선플라워씨드 오일 등을 사용할 수 있다.In addition, as the oil which can be mainly used as an oil phase component, one or more selected from vegetable oil, mineral oil, silicone oil and synthetic oil can be used. More specifically, mineral oil, cyclomethicone, squalane, octyldodecyl myristate, olive oil, Vitis binifera seed oil, macadamia nut oil, glyceryl octanoate, castor oil, ethylhexyl isononanoate, dimethicone Chicon, cyclopentasiloxane, sunflower seed oil and the like can be used.
또한, 유화 능력을 보강하기 위하여 계면활성제, 고급 알콜 등을 0.1 내지 5 중량% 첨가할 수 있다. 이러한 계면 활성제로는 비이온 계면활성제, 음이온성 계면 활성제, 양이온성 계면 활성제, 양성 계면 활성제, 인지질 등과 같은 통상적인 계면활성제를 사용할 수 있으며, 구체적으로, 소르비탄세스퀴놀리에이트, 폴리솔베이트 60, 글리세릴 스테아레이트, 친유형 글리세릴스테아레이트, 소르비탄올리에이트, 소르비탄 스테아레이트, 디이에이-세틸포스페이트, 소르비탄스테아레이트/ 슈크로스코코에이트, 글리세릴스테아레이트/폴리에틸렌글라이콜-100 스테아레이트, 세테아레스-6 올리베이트, 아라키딜알코올/베헤닐알코올/아라키딜 글루코사이드, 폴리프로필렌글라이콜-26-부테스-26/폴리에틸렌글라이콜-40 하이드로제네이티드 캐스터오일 등을 사용할 수 있다. 고급 알콜로는 탄소수가 12 내지 20인 알코올, 예컨대 세틸알코올, 스테아릴 알코올, 옥틸도데칸올, 이소스테아릴 알코올 등을 단독으로 또는 1종 이상 혼합하여 사용할 수 있다.In addition, 0.1 to 5% by weight of a surfactant, a higher alcohol, and the like may be added to reinforce the emulsifying ability. Such surfactants may be used conventional surfactants such as nonionic surfactants, anionic surfactants, cationic surfactants, amphoteric surfactants, phospholipids, and the like, specifically, sorbitan sesquinolate,
수상 성분은 수상의 점도 또는 경도를 조절하기 위하여 카보머, 잔탄검, 벤토나이트, 마그네슘알루미늄실리케이트, 셀룰로오스검, 덱스트린 팔미테이트 등과 같은 1종 이상의 점증제를 0.001 내지 5 중량% 더 첨가할 수 있다.The aqueous phase component may further add 0.001 to 5% by weight of one or more thickeners such as carbomer, xanthan gum, bentonite, magnesium aluminum silicate, cellulose gum, dextrin palmitate and the like to adjust the viscosity or hardness of the aqueous phase.
또한, 본 발명의 화장료 조성물에는 필요에 따라 고급 지방산, 비타민 등의 약효 성분과 자외선 차단제, 산화 방지제(부틸히드록시아니솔, 갈릭산프로필, 엘리소르빈산, 토코페릴아세테이드, 부틸레이티드하이드록시톨루엔 등), 방부제(메칠파라벤, 부틸파라벤, 프로필파라벤, 페녹시에탄올, 이미다졸리디닐우레아, 클로르페네신 등), 착색제, pH 조절제(트리에탄올아민, 씨트릭애씨드, 시트르산, 시트르산나트륨, 말산, 말산나트륨, 프말산, 프말산나트륨, 숙신산, 숙신산나트륨, 수산화나트륨, 인산일수소나트륨 등), 보습제(글리세린, 솔비톨, 프로필렌 글라이콜, 부틸렌 글라이콜, 헥실렌 글라이콜, 디글리세린, 베타인, 글리세레스-26, 메칠글루세스-20 등), 윤활제 등의 성분을 더 첨가할 수 있다.In addition, the cosmetic composition of the present invention, if necessary, active ingredients such as higher fatty acids, vitamins, sunscreens, antioxidants (butylhydroxyanisole, propyl gallic acid, elixolic acid, tocopheryl acetate, butylated hydroxy) Toluene, etc.), preservatives (methylparaben, butylparaben, propylparaben, phenoxyethanol, imidazolidinylurea, chlorphenesin, etc.), colorants, pH regulators (triethanolamine, citric acid, citric acid, sodium citrate, malic acid, Sodium malic acid, pmaric acid, sodium pramate, succinic acid, sodium succinate, sodium hydroxide, sodium monohydrogen phosphate, etc., moisturizers (glycerine, sorbitol, propylene glycol, butylene glycol, hexylene glycol, diglycerin , Betaine, glycerin-26, methylgluse-20 and the like), lubricants and the like can be further added.
또한, 본 발명의 화장료 조성물은 피부에 필수 영양소를 보조적으로 제공할 수 있는 물질을 추가로 포함하는데, 바람직하게는 천연향, 화장품향, 또는 한약재가 포함되지만 이들에 국한되지 않는 보조제를 함유할 수 있다.In addition, the cosmetic composition of the present invention further includes a substance capable of auxiliaryly providing essential nutrients to the skin, and may preferably contain auxiliary agents including, but not limited to, natural flavors, cosmetic flavors, or herbal medicines. have.
본 발명의 화장료 조성물에서 티아졸 또는 이의 화장품학적으로 허용 가능한 염의 유효 함량은 특별히 제한되지 않으며, 조성물 전체 중량에 대하여 0.0001 내지 20 중량%로 포함되는 것일 수 있다. 화장료 내에 0.0001 중량% 미만의 티아졸 또는 이의 염은 그 용량이 소량이어서 기대하는 개선 효과가 없을 수 있으며, 20 중량% 초과의 티아졸 또는 이의 염은 기존에 알려진 독성을 나타낼 수 있다.The effective amount of the thiazole or cosmetically acceptable salt thereof in the cosmetic composition of the present invention is not particularly limited and may be included in 0.0001 to 20% by weight based on the total weight of the composition. Less than 0.0001% by weight of thiazole or salt thereof in the cosmetic may not have the expected improvement effect due to its small amount, and more than 20% by weight of thiazole or salt thereof may exhibit known toxicity.
본 발명의 용어 "향료 조성물"은 향수, 화장품, 입욕제 등의 피부 외용 기제나 식품, 의약품 등에 배합될 수 있고, 배합량은 당업계에 통상적인 기술에 따라, 목적하는 효과를 이루기 위해 적절하게 선택하여 배합할 수 있다.The term "fragrance composition" of the present invention may be blended into skin-based bases such as perfumes, cosmetics, bathing agents, foods, pharmaceuticals, and the like, and the blending amount may be appropriately selected to achieve a desired effect according to techniques conventional in the art. It can mix.
본 발명의 향료 조성물의 제형은 특별하게 제한되지 않지만, 분말, 과립, 액상 스프레이, 고형 및 젤 타입의 제형 중에서 선택된 어느 하나일 수 있다. The formulation of the fragrance formulation of the present invention is not particularly limited, but may be any one selected from powder, granule, liquid spray, solid and gel type formulations.
상기 향료 조성물은 향수를 포함하는 화장용품, 목욕비누를 포함하는 비누세정용품, 유리 크리너를 포함하는 실내청소용품, 자동차용 방향제를 포함하는 방향용품, 허브타입 입욕제를 포함하는 목욕용품, 문구류를 포함하는 향기상품, 오피스용 방향제를 포함하는 환경용품 또는 합성수지를 포함하는 공업용품을 제조하는데 사용할 수 있다.The fragrance composition includes a cosmetic article including perfume, a soap cleaning article including a bath soap, a room cleaning article including a glass cleaner, a fragrance article including a car air freshener, a bath article containing a herbal type bath, and stationery It can be used to manufacture industrial products including fragrance products, environmental products containing office fragrances or synthetic resin.
본 발명의 향료 조성물은 향료 조성물 전체 중량을 기준으로 할 때 그 유효성분인 티아졸을, 본 발명의 향료 조성물이 구체화되는 제품 형태에 따라 0.00001 중량% 내지 10 중량%, 바람직하게는 0.00001 중량% 내지 1.0 중량%, 더 바람직하게는 0.00001 중량% 내지 0.5 중량%의 범위로 함유할 수 있다.The fragrance composition of the present invention is based on the total weight of the fragrance composition, the active ingredient of thiazole, 0.00001% to 10% by weight, preferably 0.00001% to 10% by weight depending on the product form in which the perfume composition of the present invention is specified. 1.0 wt%, more preferably 0.00001 wt% to 0.5 wt%.
상기에서 향료 조성물이 구체화되는 제품 형태는 비누, 화장품, 입욕제, 아로마 오일 등을 포함하며, 구체적으로 바디 로션, 샴푸, 헤어 린스, 헤어 컨디셔너, 헤어 트리트먼트, 발한 억제제, 스킨 로션, 스킨 크림, 방취제, 향수(스프레이제 또는 훈증제), 립스틱, 립크림, 입욕제 등을 포함하나, 이들에 한정되는 것은 아니다.Product forms in which the fragrance composition is embodied include soaps, cosmetics, baths, aroma oils, and the like, specifically, body lotions, shampoos, hair rinses, hair conditioners, hair treatments, antiperspirants, skin lotions, skin creams, deodorants , Perfumes (spray or fumigation), lipsticks, lip creams, baths and the like.
이들 제품은 혈행 촉진제, 소염제, 보습제, 수렴제, 무기 염, 유기 염, 오일성 성분, 계면활성제, 생약류, 색소, 향료, 황, 탕화(sinter deposit), 살균제 등과 같은 각종 부가제를 함유할 수 있다.These products may contain various additives such as blood circulation promoters, anti-inflammatory agents, humectants, astringents, inorganic salts, organic salts, oily ingredients, surfactants, herbals, pigments, flavorings, sulfur, sinter deposits, fungicides and the like. .
특히 본 발명의 향료 조성물은 메이크업 제품, 스킨 로션, 스킨 크림 등의 화장품 제형의 피부 외용제로 사용되는 경우가 일반적일 것인데, 이 경우에는 이들 화장품 제형에 통상적으로 사용되는 성분들을 함유할 수 있다.In particular, the fragrance composition of the present invention will generally be used as a skin external preparation of cosmetic formulations, such as makeup products, skin lotions, skin creams, in which case it may contain components commonly used in these cosmetic formulations.
특히 본 발명의 향료 조성물은 그 유효성분인 티아졸이 아토피 피부염 개선 활성을 가진다는 점에서 입욕제에 혼입되어 사용되는 것이 바람직하나. 이 경우 유효성분은 입욕제 총 중량을 기준으로 할 때 바람직하게는 0.00001 중량 내지 1 중량%, 더 바람직하게는 0.0001 내지 0.1 중량%의 범위로 포함될 수 있다. 본 발명의 향료 조성물이 입욕제에 혼입되어 사용되는 경우 그 입욕제는 목욕물에 0.015 내지 15 ppm의 농도로 첨가되어 사용될 수 있다.In particular, the fragrance composition of the present invention is preferably used in combination with the bathing agent in that the active ingredient thiazole has an atopic dermatitis improving activity. In this case, the active ingredient may be included in the range of preferably 0.00001 to 1% by weight, more preferably 0.0001 to 0.1% by weight based on the total weight of the bath. When the fragrance composition of the present invention is used incorporating into the bath, the bath may be added to the bath water at a concentration of 0.015 to 15 ppm.
입욕제는 본 발명의 향료 조성물의 유효성분 이외에 무기 염, 유기산, 오일성 성분 등을 함유할 수 있다.Bathing agent may contain an inorganic salt, an organic acid, an oily component, etc. in addition to the active ingredient of the fragrance composition of this invention.
무기염으로서는 염화나트륨, 탄산수소나트륨, 탄산나트륨, 붕사, 황산나트륨, 황화나트륨, 세스퀴탄산나트륨, 질산나트륨, 티오황산나트륨, 폴리인산나트륨, 인산나트륨, 산화칼슘, 산화마그네슘, 탄산칼슘, 탄산마그네슘, 염화칼륨, 황화칼륨 등을 예시할 수 있으며, 이들은 단독으로 또는 2종 이상의 혼합물로서 사용될 수 있다. 이들 무기 염은 입욕제 총 중량을 기준으로 5 중량% 이상, 바람직하게는 10 중량% 이상으로 입욕제에 첨가될 수 있다.Inorganic salts include sodium chloride, sodium bicarbonate, sodium carbonate, borax, sodium sulfate, sodium sulfide, sodium sesquicarbonate, sodium nitrate, sodium thiosulfate, sodium polyphosphate, sodium phosphate, calcium oxide, magnesium oxide, calcium carbonate, magnesium carbonate, potassium chloride, sulfide Potassium and the like, and these may be used alone or as a mixture of two or more thereof. These inorganic salts may be added to the bath at least 5% by weight, preferably at least 10% by weight based on the total weight of the bath.
유기산으로서는 석신산, 푸마르산, 말산, 타르타르산, 시트르산, 벤조산 등을 예시할 수 있으며, 이들은 단독으로 또는 2종 이상의 혼합물로 사용될 수 있다. 이들 유기산은 입욕제 총 중량을 기준으로 할 때 0.1 내지 50 중량%의 범위로 입욕제에 첨가될 수 있다.Examples of the organic acid include succinic acid, fumaric acid, malic acid, tartaric acid, citric acid, benzoic acid, and the like, which may be used alone or in a mixture of two or more thereof. These organic acids can be added to the bath in the range of 0.1 to 50% by weight, based on the total weight of the bath.
오일성 성분으로서는 왁스, 탄화수소, 고급 지방산, 고급 알콜, 에스테르, 실리콘 오일 등을 들 수 있다.Examples of the oily component include waxes, hydrocarbons, higher fatty acids, higher alcohols, esters, silicone oils, and the like.
입욕제는 또한 당해 기술분야에서 통상적으로 사용되는 기타 성분들을 추가로 함유할 수 있다. 이러한 성분들로서는 붕산, 메타규산, 규산 무수물과 같은 무기산; 회향풀, 은행, 생강, 감귤 껍질, 쥐오줌풀 뿌리, 박하, 인삼, 귀리 등의 생약재 분말; 콜타르 염료, 클로로필, 리보플라빈, 사프플라워, 안트라퀴논와 같은 인체에 무해한 것으로 확인된 천연 색소; 비타민 A, 비타민 C, 비타민 D, 비타민 E 등의 비타민류; 황, 운모 분말, 백토 분말, 황토 분말, 쌀겨 탄화물, 살균제, 방부제 등을 들 수 있다.The bath may also further contain other ingredients conventionally used in the art. Such components include inorganic acids such as boric acid, metasilicate and silicic anhydride; Herbal powders such as fennel, ginkgo, ginger, citrus peel, Valerian root, peppermint, ginseng, oats; Natural pigments identified as harmless to humans, such as coal tar dyes, chlorophyll, riboflavin, saffflower, anthraquinone; Vitamins such as vitamin A, vitamin C, vitamin D, and vitamin E; Sulfur, mica powder, clay powder, loess powder, rice bran carbide, fungicide, preservative and the like.
이러한 입욕제는 과립, 정제, 액제, 산제 등의 임의의 성상으로 제조될 수 있다.Such bathing agents can be prepared in any form, such as granules, tablets, solutions, powders and the like.
본 발명에서 사용되는 용어 "의약외품"은 사람이나 동물의 질병을 진단, 치료, 개선, 경감, 처치 또는 예방할 목적으로 사용되는 물품들 중 의약품보다 작용이 경미한 물품들을 의미하는 것으로, 예를 들어 약사법에 따르면 의약외품이란 의약품의 용도로 사용되는 물품을 제외한 것으로, 사람ㆍ동물의 질병 치료나 예방에 쓰이는 제품, 인체에 대한 작용이 경미하거나 직접 작용하지 않는 제품 등이 포함된다.The term "quasi drug" used in the present invention refers to articles that have a lesser action than medicines among articles used for the purpose of diagnosing, treating, ameliorating, reducing, treating, or preventing a disease of a human or animal. According to the quasi-drug product, the product used for the purpose of medicine is excluded, and it is used for the treatment or prevention of diseases of humans and animals, and the products that have little or no direct action on the human body.
본 발명의 의약외품 조성물은 알러지성 질환 또는 아토피 피부염의 예방 또는 개선을 목적으로 사용되는 것으로, 그 제형에 있어서 특별히 한정되는 바가 없으며, 예를 들면, 유연화장수, 영양화장수, 마사지크림, 영양크림, 팩, 마스크팩, 마스크시트, 젤 또는 피부 점착타입 화장료의 제형을 갖는 화장료 조성물일 수 있으며, 또한, 로션, 연고, 겔, 크림, 패취 또는 분무제와 같은 경피투여형 제형일 수 있다.The quasi-drug composition of the present invention is used for the purpose of preventing or improving allergic diseases or atopic dermatitis, and is not particularly limited in the formulation, for example, softening water, nourishing cosmetics, massage cream, nutrition cream, pack It may be a cosmetic composition having a formulation of a mask pack, a mask sheet, a gel or a skin adhesive cosmetic, and may also be a transdermal formulation such as a lotion, an ointment, a gel, a cream, a patch or a spray.
또한, 각 제형에 있어서 의약외품 조성물은 다른 성분들을 기타 의약외품의 제형 또는 사용목적 등에 따라 임의로 선정하여 배합할 수 있다. 유효 성분의 혼합양은 사용 목적(억제 또는 완화)에 따라 적합하게 결정될 수 있다. 예를 들어, 점증제, 안정화제, 용해화제, 비타민, 안료 및 향료와 같은 통상적인 보조제, 및 담체 등을 포함할 수 있다.In addition, in each formulation, the quasi-drug composition may be optionally selected and blended with other ingredients according to the formulation or purpose of use of the other quasi-drug. The mixed amount of the active ingredient can be suitably determined according to the purpose of use (inhibition or relaxation). For example, thickeners, stabilizers, solubilizers, conventional adjuvants such as vitamins, pigments and flavors, and carriers and the like.
본 발명의 티아졸 또는 이의 염의 함량은 의약외품 조성물의 총 중량을 기준으로 각각 0.0001 내지 20 중량%인 것이 바람직하다. 20 중량%를 초과하는 경우에는 조성물 제조 시 색상 및 안정성이 떨어질 수 있고, 0.0001% 미만의 경우에는 그 작용효과가 미미하다.The content of the thiazole or salt thereof of the present invention is preferably 0.0001 to 20% by weight, respectively, based on the total weight of the quasi-drug composition. If the content exceeds 20% by weight, the color and stability of the composition may be degraded. If the content is less than 0.0001%, the effect is minimal.
또한, 각 제형의 의약외품 조성물에 있어서, 상기한 필수 성분 이외의 다른 성분들은 제형 또는 사용목적 등에 따라 당업자가 어려움 없이 적의 선정하여 배합할 수 있다.In addition, in the quasi-drug composition of each formulation, other components than the essential components described above can be appropriately selected and blended by those skilled in the art without difficulty according to the formulation or purpose of use.
이하, 실시예를 통하여 본 발명을 더욱 상세하게 설명하고자 한다. 이들 실시예는 오로지 본 발명을 예시하기 위한 것으로서, 본 발명의 범위가 이들 실시예에 의해 제한되는 것으로 해석되지 않는 것은 당업계에서 통상의 지식을 가진 자에게 있어서 자명할 것이다.Below, Through the examples will be described in more detail the present invention. These examples are only for illustrating the present invention, and it will be apparent to those skilled in the art that the scope of the present invention is not to be construed as being limited by these examples.
실시예 : 비만세포 및 각질형성세포에 티아졸(Thiazole) 처리 후 염증 관련 사이토카인의 분비 및 발현 평가Example: Evaluation of Secretion and Expression of Inflammation-Related Cytokines After Thiazole Treatment in Mast Cells and Keratinocytes
1-1. 실험방법1-1. Experiment method
1) 비만세포 세포배양1) Mast Cell Culture
비만세포(rat basophilic leukemia cell line, RBL-2H3)는 ATCC사(Manassas, VA, USA)로부터 구매하여 사용하였다. 10% heat-inactivated FBS(feta bovine serum)(Gibco BRL, USA)과 1% 페니실린(penicillin) 및 스트렙토마이신(streptomycin; Gibco BRL, USA)을 포함한 DMEM(Dulbecco modified eagle medium)(Gibco BRL, USA) 배양액에서 세포를 배양하였다. 세포는 37℃, 5% CO2 조건하에서 배양하여 실험하였다. 비만세포를 10% FBS가 포함된 DMEM에 현탁시킨 후 6 웰 플레이트(well plate; Corning, USA)에 1×106 cells/ml의 세포수가 되도록 분주하였다. Mast cells (rat basophilic leukemia cell line, RBL-2H3) were purchased from ATCC (Manassas, VA, USA). Dulbecco modified eagle medium (Gibco BRL, USA) containing 10% heat-inactivated febo bovine serum (FBS) (Gibco BRL, USA) and 1% penicillin and streptomycin (Gibco BRL, USA) Cells were cultured in culture. Cells were tested by incubating at 37 ° C. and 5% CO 2 . Mast cells were suspended in DMEM containing 10% FBS and then aliquoted into 6 well plates (Corning, USA) to a cell number of 1 × 10 6 cells / ml.
그 후 anti DNP(dinitrophenyl)-IgE(100 ng/ml)로 감작하고 37℃, 5% CO2 인큐베이터에서 24시간 동안 배양하였다. PBS(phosphate buffered saline)로 2회 세척한 다음 DNP-HSA(dinitrophenylated human serum albumin; 100 ng/ml)를 1시간 동안 처리하여 면역반응을 유도하였다. 이때 티아졸(Thiazole)에 의한 아토피 개선효능을 평가하기 위해 anti DNP(dinitrophenyl)-IgE를 처리하는 동시에 티아졸 (100 μM)을 처리하여 24시간 동안 배양한 다음 DNP-HSA로 면역반응을 유도하였다. 음성대조세포의 경우 티아졸 대신 DMSO로 처리하여 24시간 동안 배양한 후 DNP-HSA로 면역반응을 유도하였다.It was then sensitized with anti DNP (dinitrophenyl) -IgE (100 ng / ml) and incubated for 24 hours in a 37 ℃, 5% CO 2 incubator. After washing twice with PBS (phosphate buffered saline), DNP-HSA (dinitrophenylated human serum albumin; 100 ng / ml) was treated for 1 hour to induce an immune response. At this time, anti-DNP (dinitrophenyl) -IgE treatment and thiazole (100 μM) were incubated for 24 hours to induce an atopy improvement effect by thiazole. Then, the immune response was induced by DNP-HSA. . Negative control cells were treated with DMSO instead of thiazole and incubated for 24 hours to induce an immune response with DNP-HSA.
2) 각질형성세포 세포배양2) Keratinocytes Cell Culture
각질형성세포(human keratinocyte cell line, HaCaT)는 ATCC사(Manassas, VA, USA)로부터 구매하여 사용하였다. 10% FBS(fetal bovine serum)와 항생제가 들어있는 DMEM 배양액을 사용하여 세포를 배양하였다. 배양 용기는 75T-플라스크(flask)와 6 웰 플레이트를 사용하였으며 5% CO₂가 공급되는 37℃ 배양기에서 배양하였다. 배양액은 3~4일마다 교환해 주며 세포가 과다하게 증식되었을 때는 계대배양 하였다. 분주된 HaCaT 세포(5×105/well)를 24시간 배양한 후 PBS로 세척하였다. 각질형성세포에 면역반응을 유도하기 위해 FBS를 넣지 않은 DMEM 배지에 TNF-α(tumor necrosis factor-α)(10 ng/ml) 및 IFN-γ(interferon gamma)(10 ng/ml)를 함께 처리하여 24 시간동안 배양하였다. 이때 티아졸에 의한 면역반응 개선효능을 평가하기 위해 티아졸 100 μM을 면역반응 유도물질과 동시에 처리하였으며, 음성대조세포의 경우 티아졸 대신 DMSO를 면역반응 유도물질과 동시에 처리하고 24시간 동안 배양하였다.Human keratinocyte cell line (HaCaT) was purchased from ATCC (Manassas, VA, USA). Cells were cultured using DMEM medium containing 10% FBS (fetal bovine serum) and antibiotics. The culture vessel used a 75T-flask and 6 well plates and incubated in a 37 ° C. incubator fed with 5% CO 2. The cultures were exchanged every 3 to 4 days and subcultured when the cells proliferated excessively. Aliquoted HaCaT cells (5 × 10 5 / well) were incubated for 24 hours and washed with PBS. Treatment of TNF-α (tumor necrosis factor-α) (10 ng / ml) and IFN-γ (interferon gamma) (10 ng / ml) in DMEM medium without FBS to induce an immune response to keratinocytes Incubated for 24 hours. At this time, 100 μM of thiazole was simultaneously treated with the immune response inducer to evaluate the effect of improving the immune response by thiazole, and in the case of negative control cells, DMSO was simultaneously treated with the immune response inducer instead of thiazole and incubated for 24 hours. .
3) 히스타민 분비량 측정(Histamine release assay)3) Histamine release assay
면역반응을 유도한 비만세포에서 분비되는 히스타민의 농도를 측정하기 위하여 아이스 배스(ice bath)에서 10분간 정치하여 면역 반응을 종결시킨 후 배양액을 10,000 xg에서 10분간 원심분리한 후, 상층액을 취하여 96-웰 플레이트에 옮겼다. 히스타민 정량은 ENZO사의 히스타민 측정 키트(histamine release assay ELISA kit)를 이용하였으며 인피니트 M200 프로 마이크로플레이트 리더(Infinite M200 pro microplate reader, TECAN) 450nm 파장에서 측정하였다. In order to measure the concentration of histamine secreted from the mast cells which induced the immune response, the reaction was terminated by standing in an ice bath for 10 minutes to terminate the immune reaction.The culture solution was centrifuged at 10,000 xg for 10 minutes, and then the supernatant was taken. Transfer to 96-well plate. Histamine quantification was performed using a histamine release assay ELISA kit from ENZO, and measured at 450 nm wavelength of Infinite M200 pro microplate reader (TECAN).
4) 트리졸 방법(Trizol method)을 이용한 RNA 분리 및 real-time PCR (quantitative reverse-transcription polymerase chain reacion)4) RNA isolation and real-time PCR (quantitative reverse-transcription polymerase chain reacion) using Trizol method
면역반응을 유도한 비만세포의 상층액을 제거한 후 1 ml의 트리졸을 넣고 2분간 방치한 후 클로로포름(chloroform)을 넣고 10초간 볼텍싱(vortexing)하고 2,400 xg에서 10분간 원심분리한 후, 상층액을 취하여 동량의 이소프로판올(isopropanol)을 혼합하여 흔들어 주었다. 16,000 xg에서 25분간 원심분리하여 상층액을 제거하고 펠릿(pellet)은 DEPC(diethyl pyrocarbonate)-DW 20μl에 녹여 -20℃에 보관하였다가 실험에 사용하였다. RT-PCR은 one-step RT-PCR PreMix kit(iNtRON Biotechnology, Korea)를 사용하여 45℃에서 30분, 94℃에서 5분간 반응시킨 후 94℃에서 30초간 변성(denaturation)시키고, 55℃에서 30초간 어닐링(annealing)시킨 다음, 72℃에서 1분간 신장(extension)시키는 사이클(cycle)을 32회 반복한 뒤, 마지막 신장(extension)은 72℃에서 5분간 수행하고 PiQ SYBR green supermix (Bio-Rad)와 CFX Connect™ Real-Time PCR Detection System (Bio-Rad)을 사용하여 정량적 PCR을 수행하였으며, 이때 사용된 프라이머 서열(primer sequence)은 [표 1]에 제시된 바와 같다.After removing the supernatant of the induced immune cells, 1 ml of trizol was added and allowed to stand for 2 minutes, followed by chloroform for 10 seconds, vortexed for 10 seconds, and centrifuged at 2,400 xg for 10 minutes. The solution was taken and the same amount of isopropanol was mixed and shaken. The supernatant was removed by centrifugation at 16,000 xg for 25 minutes, and pellets were dissolved in DEPC (diethyl pyrocarbonate) -DW 20μl and stored at -20 ° C. RT-PCR was reacted for 30 minutes at 45 ° C and 5 minutes at 94 ° C using a one-step RT-PCR PreMix kit (iNtRON Biotechnology, Korea), followed by denaturation at 94 ° C for 30 seconds, and 30 ° at 55 ° C. After annealing for 2 seconds, 32 cycles of 1 minute extension at 72 ° C., the last extension was performed at 72 ° C. for 5 minutes, followed by PiQ SYBR green supermix (Bio-Rad). ) And CFX Connect ™ Real-Time PCR Detection System (Bio-Rad) were used for quantitative PCR, wherein the primer sequences used are shown in Table 1.
(℃)Annealing temperature
(℃)
생성물 (bp)PCR
Product (bp)
1-2. 실험결과1-2. Experiment result
1) 히스타민 분비량 변화1) Change in histamine secretion
활성화된 비만세포로부터 탈과립에 의해 분비되는 히스타민에 대한 티아졸의 효과를 확인하기 위해 세포배양액으로부터 히스타민의 농도를 효소면역반응법으로 측정하였다. 그 결과, anti DNP(dinitrophenyl)-IgE로 감작하고 DNP-HSA로 면역반응을 유도한 대조세포에서는 정상 비만세포에 비해 히스타민 농도가 유의적으로 증가하였다. 한편, anti DNP(dinitrophenyl)-IgE 및 DNP-HSA에 의한 면역반응을 유도하면서 티아졸을 처리한 결과, 히스타민의 농도가 유의하게 감소되었다(도 1).In order to confirm the effect of thiazole on histamine released by degranulation from activated mast cells, the concentration of histamine from the cell culture was measured by enzyme-immunoassay. As a result, the control cells which sensitized with anti DNP (dinitrophenyl) -IgE and induced the immune response with DNP-HSA significantly increased histamine concentrations compared to normal mast cells. On the other hand, as a result of treatment with thiazole while inducing an immune response by anti DNP (dinitrophenyl) -IgE and DNP-HSA, the concentration of histamine was significantly decreased (FIG. 1).
2) 비만세포에서의 염증성 사이토카인 생성 변화2) Inflammatory cytokine production in mast cells
anti DNP(dinitrophenyl)-IgE로 감작하고 DNP-HSA로 면역반응을 유도한 대조세포에서는 정상 비만세포에 비해 염증성 사이토카인인 IL-4, IL-13 및 TNF-α의 발현이 유의적으로 증가하였다. 한편, anti DNP(dinitrophenyl)-IgE 및 DNP-HSA에 의한 면역반응을 유도하면서 티아졸을 처리한 결과, 면역반응으로 인해 증가된 염증성 사이토카인(IL-4, IL-13 및 TNF-α)의 발현이 모두 유의하게 감소되었다(도 2).In control cells sensitized with anti DNP (dinitrophenyl) -IgE and induced immune response with DNP-HSA, expression of inflammatory cytokines IL-4, IL-13 and TNF-α was significantly increased compared to normal mast cells. . On the other hand, treatment with thiazole while inducing an immune response by anti DNP (dinitrophenyl) -IgE and DNP-HSA resulted in an increase in inflammatory cytokines (IL-4, IL-13 and TNF-α) due to the immune response. Both expressions were significantly reduced (FIG. 2).
3) 각질형성세포에서의 염증성 사이토카인 생성 변화3) Inflammatory cytokine production in keratinocytes
TNF-α 및 IFN-γ로 면역반응을 유도시킨 대조세포에서는 정상 각질형성세포에 비해 염증성 사이토카인인 IL-1β, IL-6 및 IL-8의 발현이 유의적으로 증가하였다. 한편, TNF-α 및 IFN-γ과 함께 티아졸을 각질형성세포에 처리한 결과, 면역반응으로 인해 증가된 염증성 사이토카인(IL-1β, IL-6 및 IL-8)의 발현이 모두 유의하게 감소되었다(도 3).In control cells induced with TNF-α and IFN-γ, expression of inflammatory cytokines IL-1β, IL-6 and IL-8 was significantly increased compared to normal keratinocytes. On the other hand, the treatment of keratinocytes with thiazole together with TNF-α and IFN-γ resulted in significantly increased expression of inflammatory cytokines (IL-1β, IL-6 and IL-8) due to immune responses. Decreased (FIG. 3).
이하, 본 발명에 따른 상기 티아졸을 유효성분으로 함유하는 의약품, 식품 또는 화장품의 제조예를 설명하나, 본 발명은 이를 한정하고자 함이 아닌 단지 구체적으로 설명하고자 함이다. 상기 알러지성 질환 또는 아토피 피부염의 예방 및 치료(또는 예방 및 개선 효과) 효과가 우수한 티아졸을 이용하여, 하기와 같은 조성성분 및 조성비에 따라, 제조예 1 내지 3의 의약품, 식품 또는 화장료 조성물을 통상적인 방법에 따라서 제조하였다.Hereinafter, a description will be given of the preparation of medicines, foods or cosmetics containing the thiazole according to the present invention as an active ingredient, but the present invention is not intended to be limited thereto, but is intended to be described in detail. Using the thiazole excellent in the prevention and treatment (or prevention and improvement effect) effect of the allergic disease or atopic dermatitis, the pharmaceutical, food or cosmetic composition of Preparation Examples 1-3 It was prepared according to the conventional method.
[제조예 1] 약학적 조성물의 제조Preparation Example 1 Preparation of Pharmaceutical Composition
<1-1> 산제의 제조<1-1> Preparation of Powder
티아졸 20 ㎎Thiazole 20 mg
유당수화물 100 ㎎
탈크 10 ㎎Talc 10 mg
상기의 성분들을 혼합하고 기밀포에 충진하여 산제를 제조하였다.The above ingredients were mixed and filled in airtight cloth to prepare a powder.
<1-2> 정제의 제조<1-2> Preparation of Tablet
티아졸 10 ㎎Thiazole 10 mg
옥수수전분 100 ㎎
유당수화물 100 ㎎
스테아르산마그네슘 2 ㎎Magnesium stearate 2mg
상기의 성분을 혼합한 후, 통상의 정제의 제조방법에 따라서 타정하여 정제를 제조하였다.After mixing the above components, tablets were prepared by tableting according to a conventional method for producing tablets.
<1-3> 캅셀제의 제조<1-3> Preparation of capsule
티아졸 10 ㎎Thiazole 10 mg
미결정셀룰로오스 3 ㎎ 3 mg of microcrystalline cellulose
유당수화물 14.8 ㎎Lactose carb 14.8 mg
스테아르산마그네슘 0.2 ㎎Magnesium Stearate 0.2 mg
상기의 성분을 혼합한 후, 통상의 캅셀제의 제조방법에 따라서 젤라틴캡슐에 충전하여 캅셀제를 제조하였다.After mixing the above components, it was filled in gelatin capsules in accordance with a conventional method for producing a capsule to prepare a capsule.
<1-4> 주사제의 제조<1-4> Preparation of Injection
티아졸 10 ㎎Thiazole 10 mg
만니톨 180 ㎎Mannitol 180 mg
주사용 멸균 증류수 2974 ㎎Sterile distilled water for injection 2974 mg
인산일수소나트륨 26 ㎎Sodium dihydrogen phosphate 26 mg
상기의 성분을 혼합한 후, 통상의 주사제의 제조방법에 따라 1앰플당(2mL) 상기의 성분 함량으로 제조하였다.After mixing the above components, it was prepared in the above component content per ampoules (2 mL) according to the conventional method for preparing injections.
<1-5> 액제의 제조<1-5> Preparation of Liquid
티아졸 10 ㎎Thiazole 10 mg
이성화당 10 ㎎Isomerized sugar 10 mg
만니톨 5 ㎎Mannitol 5 mg
정제수 적량Purified water
레몬향 적량Lemon flavor
상기의 성분을 통상의 제조방법에 따라 정제수에 각각의 성분을 가하여 용해시키고 레몬향을 적량 가한 다음 정제수를 가하여 전체 100mL로 조절한 후 멸균시켜 갈색병에 충진하여 액제를 제조한다. According to a conventional manufacturing method, each component is added to purified water to dissolve, lemon flavor is added thereto, and then purified water is added to adjust the total amount to 100 mL and sterilized to fill a brown bottle to prepare a liquid formulation.
[제조예 2] 건강식품의 제조Preparation Example 2 Preparation of Health Food
<2-1> 건강보조식품의 제조<2-1> Preparation of Health Supplements
티아졸 10 ㎎Thiazole 10 mg
비타민 혼합물 적량Vitamin Mixture
비타민 A 아세테이드 70 ㎍70 μg of Vitamin A Acetate
비타민 E 1.0 ㎎Vitamin E 1.0 mg
비타민 B1 0.13 ㎎Vitamin B 1 0.13 mg
비타민 B2 0.15 ㎎Vitamin B 2 0.15 mg
비타민 B6 0.5 ㎎Vitamin B 6 0.5 mg
비타민 B12 0.2 ㎍0.2 μg of vitamin B 12
비타민 C 10 ㎎Vitamin C 10 mg
비오틴 10 ㎍10 μg biotin
니코틴산아미드 1.7 ㎎Nicotinamide 1.7 mg
엽산 50 ㎍50 μg folic acid
판토텐산 칼슘 0.5 ㎎Calcium Pantothenate 0.5mg
무기질 혼합물 적량Mineral mixture
황산제1철 1.75 ㎎Ferrous Sulfate 1.75 mg
산화아연 0.82 ㎎Zinc Oxide 0.82 mg
탄산마그네슘 25.3 ㎎Magnesium carbonate 25.3 mg
제1인산칼륨 15 ㎎Potassium phosphate monobasic 15 mg
제2인산칼슘 55 ㎎
구연산칼륨 30 ㎎Potassium Citrate 30 mg
탄산칼슘 100 ㎎
염화마그네슘 24.8 ㎎Magnesium chloride 24.8 mg
상기의 비타민 및 미네랄 혼합물의 조성비는 비교적 건강식품에 적합한 성분을 바람직한 실시예로 혼합 조성하였지만, 그 배합비를 임의로 변형 실시하여도 무방하며, 통상의 건강식품 제조방법에 따라 상기의 성분을 혼합한 다음, 과립을 제조하고, 통상의 방법에 따라 건강식품 조성물 제조에 사용할 수 있다.Although the composition ratio of the above-mentioned vitamin and mineral mixtures is mixed with a composition suitable for a health food in a preferred embodiment, the compounding ratio may be arbitrarily modified, and the above ingredients are mixed according to a conventional health food manufacturing method. The granules may be prepared and used for preparing a health food composition according to a conventional method.
<2-2> 건강음료의 제조<2-2> Preparation of health drink
티아졸 10 mgThiazole 10 mg
비타민 C 15 g15 g of vitamin C
비타민 E(분말) 100 g100 g of vitamin E (powder)
젖산철 19.75 gIron lactate 19.75 g
산화아연 3.5 g3.5 g of zinc oxide
니코틴산아미드 3.5 g3.5 g of nicotinic acid amide
비타민 A 0.2 g0.2 g of vitamin A
비타민 B1 0.25 g0.25 g of vitamin B1
비타민 B2 0.3 g0.3 g of vitamin B2
정제수 정량Purified Water Quantification
통상의 건강음료 제조방법에 따라 상기의 성분을 혼합한 다음, 약 1시간 동안 85℃에서 교반 가열한 후, 만들어진 용액을 여과하여 멸균된 2ℓ 용기에 취득하여 밀봉 멸균한 뒤 냉장 보관한 다음 본 발명의 건강음료 조성물 제조에 사용한다.After mixing the above components in accordance with a conventional healthy beverage production method, and then stirred and heated at 85 ℃ for about 1 hour, the resulting solution is filtered and obtained in a sterilized 2 L container sealed sterilization and then refrigerated and stored in the present invention For the preparation of healthy beverage compositions.
상기 조성비는 비교적 기호음료에 적합한 성분을 바람직한 실시예로 혼합 조성하였지만 수요계층이나, 수요국가, 사용용도 등 지역적, 민족적 기호도에 따라서 그 배합비를 임의로 변형 실시하여도 무방하다.Although the composition ratio is mixed with a component suitable for a favorite beverage in a preferred embodiment, the compounding ratio may be arbitrarily modified according to regional and ethnic preferences such as demand hierarchy, demand country, and usage.
[제조예 3] 화장료 조성물의 제조Preparation Example 3 Preparation of Cosmetic Composition
하기에 본 발명의 추출물을 함유하는 화장료 조성물의 제조예를 설명하나, 본 발명은 이를 한정하고자 함이 아닌 단지 구체적으로 설명하고자 함이다.Hereinafter, an example of preparation of a cosmetic composition containing an extract of the present invention will be described, but the present invention is not intended to be limited thereto, but is intended to be described in detail.
<3-1> 영양화장수(밀크로션)<3-1> Nutrients (Milk Lotion)
티아졸 2.0 중량%Thiazole 2.0 wt%
스쿠알란 5.0 중량%Squalane 5.0 wt%
밀납 4.0 중량%Beeswax 4.0 wt%
폴리솔베이트60 1.5 중량%Polysorbate60 1.5 wt%
솔비탄세스퀴올레이트 1.5 중량%Sorbanthesquioleate 1.5 wt%
유동파라핀 0.5 중량%0.5% by weight of liquid paraffin
카프릴릭/카프릭트리글리세라이드 5.0 중량%Caprylic / Capric Triglycerides 5.0 wt%
글리세린 3.0 중량%Glycerin 3.0 wt%
부틸렌글리콜 3.0 중량%Butylene Glycol 3.0 wt%
프로필렌글리콜 3.0 중량%Propylene Glycol 3.0 wt%
카르복시비닐폴리머 0.1 중량%Carboxy vinyl polymer 0.1 wt%
트리에탄올아민 0.2 중량%0.2% by weight of triethanolamine
방부제, 색소, 향료 적량Preservatives, colorings, flavors
정제수 to 100 중량%Purified water to 100% by weight
상기의 배합비는 비교적 영양화장수에 적합한 성분을 바람직한 실시예로 혼합 조성하였지만, 그 배합비를 임의로 변형 실시하여도 무방하며, 통상적인 화장품 분야에서의 제조방법에 따라 제조할 수 있다. Although the above-mentioned compounding ratio is mixed with a component suitable for nutritional longevity in a preferred embodiment, the compounding ratio may be arbitrarily modified, and can be prepared according to the manufacturing method in the general cosmetic field.
<3-2> 유연화장수(스킨로션)<3-2> Softener (skin lotion)
티아졸 2.0 중량 %Thiazole 2.0% by weight
글리세린 3.0 중량 %Glycerin 3.0 wt%
부틸렌글리콜 2.0 중량 %Butylene glycol 2.0% by weight
프로필렌글리콜 2.0 중량 %Propylene Glycol 2.0 wt%
카르복시비닐폴리머 0.1 중량 %Carboxy vinyl polymer 0.1 wt%
PEG 12 노닐페닐에테르 0.2 중량 %PEG 12 nonylphenylether 0.2% by weight
폴리솔베이트80 0.4 중량 %
에탄올 10.0 중량 %Ethanol 10.0 wt%
트리에탄올아민 0.1 중량 %Triethanolamine 0.1% by weight
방부제, 색소, 향료 적량Preservatives, colorings, flavors
정제수 to 100 중량 %Purified water to 100% by weight
상기의 배합비는 비교적 유연화장수에 적합한 성분을 바람직한 실시예로 혼합 조성하였지만, 그 배합비를 임의로 변형 실시하여도 무방하며, 통상적인 화장품 분야에서의 제조방법에 따라 제조할 수 있다. Although the above-mentioned compounding ratio is mixed and formulated in a preferred embodiment with a component suitable for a relatively softening longevity, the compounding ratio may be arbitrarily modified, and can be prepared according to the manufacturing method in the general cosmetic field.
<3-3> 영양크림<3-3> nutrition cream
티아졸 2.0 중량 % Thiazole 2.0% by weight
폴리솔베이트60 1.5 중량 %Polysorbate60 1.5 wt%
솔비탄세스퀴올레이트 0.5 중량 %Solbitan Sesquioleate 0.5% by weight
PEG60 경화피마자유 2.0 중량 %PEG60 Cured Castor Oil 2.0% by weight
유동파라핀 10 중량 %10% by weight of liquid paraffin
스쿠알란 5.0 중량 %Squalane 5.0 wt%
카프릴릭/카프릭트리글리세라이드 5.0 중량 %Caprylic / Capric Triglycerides 5.0 wt%
글리세린 5.0 중량 %Glycerin 5.0 wt%
부틸렌글리콜 3.0 중량 %Butylene glycol 3.0% by weight
프로필렌글리콜 3.0 중량 %Propylene Glycol 3.0 Weight%
트리에탄올아민 0.2 중량 %Triethanolamine 0.2% by weight
방부제 적량Preservative
색소 적량Pigment amount
향료 적량Spices
정제수 to 100 중량 %Purified water to 100% by weight
상기의 배합비는 비교적 영양크림에 적합한 성분을 바람직한 실시예로 혼합 조성하였지만, 그 배합비를 임의로 변형 실시하여도 무방하며, 통상적인 화장품 분야에서의 제조방법에 따라 제조할 수 있다. Although the above-mentioned compounding ratio is mixed with a component suitable for nourishing cream in a preferred embodiment, the compounding ratio may be arbitrarily modified, and can be prepared according to a conventional manufacturing method in the cosmetic field.
<3-4> 마사지크림<3-4> massage cream
티아졸 1.0 중량 %Thiazole 1.0% by weight
밀납 10.0 중량 %Beeswax 10.0 weight%
폴리솔베이트60 1.5 중량 %Polysorbate60 1.5 wt%
PEG 60 경화피마자유 2.0 중량 %
솔비탄세스퀴올레이트 0.8 중량 %Sorbanthesquioleate 0.8 wt%
유동파라핀 40.0 중량 %40.0% by weight of liquid paraffin
스쿠알란 5.0 중량 %Squalane 5.0 wt%
카프릴릭/카프릭트리글리세라이드 4.0 중량 %Caprylic / Capric Triglyceride 4.0 wt%
글리세린 5.0 중량 %Glycerin 5.0 wt%
부틸렌글리콜 3.0 중량 %Butylene glycol 3.0% by weight
프로필렌글리콜 3.0 중량 %Propylene Glycol 3.0 Weight%
트리에탄올아민 0.2 중량 %Triethanolamine 0.2% by weight
방부제, 색소, 향료 적량Preservatives, colorings, flavors
정제수 to 100 중량 %Purified water to 100% by weight
상기의 배합비는 비교적 마사지크림에 적합한 성분을 바람직한 실시예로 혼합 조성하였지만, 그 배합비를 임의로 변형 실시하여도 무방하며, 통상적인 화장품 분야에서의 제조방법에 따라 제조할 수 있다. Although the above-mentioned compounding ratio is mixed with a component suitable for a massage cream in a preferred embodiment, the compounding ratio may be arbitrarily modified, and can be prepared according to a conventional manufacturing method in the cosmetic field.
<3-5> 팩<3-5> pack
티아졸 1.0 중량 %Thiazole 1.0% by weight
폴리비닐알콜 13.0 중량 %Polyvinyl alcohol 13.0 wt%
소듐카르복시메틸셀룰로오스 0.2 중량 %Sodium Carboxymethylcellulose 0.2% by weight
글리세린 5.0 중량 %Glycerin 5.0 wt%
알란토인 0.1 중량 %Allantoin 0.1 wt%
에탄올 6.0 중량 %Ethanol 6.0 wt%
PEG 12 노닐페닐에테르 0.3 중량 %PEG 12 nonylphenylether 0.3 wt%
폴리솔베이트60 0.3 중량 %Polysorbate60 0.3 wt%
방부제, 색소, 향료 적량Preservatives, colorings, flavors
정제수 to 100 중량 %Purified water to 100% by weight
상기의 배합비는 비교적 팩에 적합한 성분을 바람직한 실시예로 혼합 조성하였지만, 그 배합비를 임의로 변형 실시하여도 무방하며, 통상적인 화장품 분야에서의 제조방법에 따라 제조할 수 있다. Although the above-mentioned compounding ratio is mixed with a component suitable for a pack in a preferred embodiment, the compounding ratio may be arbitrarily modified, and can be prepared according to a manufacturing method in the general cosmetic field.
<3-6> 젤<3-6> gel
티아졸 0.5 중량 %Thiazole 0.5% by weight
에틸렌디아민초산나트륨 0.05 중량 %Ethylenediamine sodium acetate 0.05% by weight
글리세린 5.0 중량 %Glycerin 5.0 wt%
카르복시비닐폴리머 0.3 중량 %Carboxy vinyl polymer 0.3 wt%
에탄올 5.0 중량 %Ethanol 5.0 wt%
PEG 60 경화피마자유 0.5 중량 %
트리에탄올아민 0.3 중량 %0.3% by weight of triethanolamine
방부제, 색소, 향료 적량Preservatives, colorings, flavors
정제수 to 100 중량 %Purified water to 100% by weight
상기의 배합비는 비교적 젤에 적합한 성분을 바람직한 실시예로 혼합 조성하였지만, 그 배합비를 임의로 변형 실시하여도 무방하며, 통상적인 화장품 분야에서의 제조방법에 따라 제조할 수 있다. Although the above-mentioned compounding ratio is mixed with a component suitable for a gel in a preferred embodiment, the compounding ratio may be arbitrarily modified, and can be prepared according to a manufacturing method in the general cosmetic field.
상기 배합비는 비교적 화장료 조성물에 적합한 성분을 바람직한 실시예로 혼합 조성하였지만, 그 외의 색채 화장품을 포함하는 다양한 용도의 화장품에 적용될 수 있는 것이고, 그 효능에 따라 인체에 얇게 도포하여 바를 수 있는 약제 즉, 연고로 제조에 이용될 수 있으며 수요계층이나, 수요국가, 사용용도 등 지역적, 민족적 기호도에 따라서 그 배합비를 임의로 변형 실시하여도 무방하다.The blending ratio is a relatively suitable composition for the cosmetic composition in a preferred embodiment, but can be applied to cosmetics of various uses, including other color cosmetics, according to the efficacy of the drug that can be applied to a thin coating on the human body, that is, It can be used for manufacturing as ointment, and the compounding ratio may be arbitrarily modified according to regional and ethnic preferences such as demand hierarchy, demand country, and usage.
전술한 본 발명의 설명은 예시를 위한 것이며, 본 발명이 속하는 기술분야의 통상의 지식을 가진 자는 본 발명의 기술적 사상이나 필수적인 특징을 변경하지 않고서 다른 구체적인 형태로 쉽게 변형이 가능하다는 것을 이해할 수 있을 것이다. 그러므로 이상에서 기술한 실시예들은 모든 면에서 예시적인 것이며 한정적이 아닌 것으로 이해해야만 한다.The foregoing description of the present invention is intended for illustration, and it will be understood by those skilled in the art that the present invention may be easily modified into other specific forms without changing the technical spirit or essential features of the present invention. will be. Therefore, it should be understood that the embodiments described above are exemplary in all respects and not restrictive.
<110> Industry-Academic Cooperation Foundation, Yonsei University <120> COMPOSITION INCLUDING THIAZOLE OR SALT THEREOF AS ACTIVE INGREDIENTS FOR PREVENTING OR TREATING ALLERGIC DISEASE OR ATOPIC DERMATITIS <130> 1065541 <160> 14 <170> KoPatentIn 3.0 <210> 1 <211> 22 <212> DNA <213> Artificial Sequence <220> <223> IL-4_F primer <400> 1 cagggtgctt cgcaaatttt ac 22 <210> 2 <211> 21 <212> DNA <213> Artificial Sequence <220> <223> IL-4_R primer <400> 2 accgagaacc ccagacttgt t 21 <210> 3 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> IL-13_F primer <400> 3 ggtggcctca cctccccaag 20 <210> 4 <211> 25 <212> DNA <213> Artificial Sequence <220> <223> IL-13_R primer <400> 4 gatgacactg cagttggaga tgctg 25 <210> 5 <211> 21 <212> DNA <213> Artificial Sequence <220> <223> TNF-alpha_F primer <400> 5 cagccgattt gccacttcat a 21 <210> 6 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> TNF-alpha_R primer <400> 6 tccttagggc aagggctctt 20 <210> 7 <211> 21 <212> DNA <213> Artificial Sequence <220> <223> IL-1beta_F primer <400> 7 ttacagtggc aatgaggatg a 21 <210> 8 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> IL-1beta_R primer <400> 8 tgtagtggtg gtcggagatt 20 <210> 9 <211> 26 <212> DNA <213> Artificial Sequence <220> <223> IL-6_F primer <400> 9 cctgagaaag gagacatgta acaaga 26 <210> 10 <211> 23 <212> DNA <213> Artificial Sequence <220> <223> IL-6_R primer <400> 10 tggaaggttc aggttgtttt ctg 23 <210> 11 <211> 18 <212> DNA <213> Artificial Sequence <220> <223> IL-8_F primer <400> 11 ctggccgtgg ctctcttg 18 <210> 12 <211> 22 <212> DNA <213> Artificial Sequence <220> <223> IL-8_R primer <400> 12 ttagcactcc ttggcaaaac tg 22 <210> 13 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> beta-actin_F primer <400> 13 accgtgaaaa gatgacccag 20 <210> 14 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> beta-actin_R primer <400> 14 tgtcagctgt ggtggtgaag 20 <110> Industry-Academic Cooperation Foundation, Yonsei University <120> COMPOSITION INCLUDING THIAZOLE OR SALT THEREOF AS ACTIVE INGREDIENTS FOR PREVENTING OR TREATING ALLERGIC DISEASE OR ATOPIC DERMATITIS <130> 1065541 <160> 14 <170> KoPatentIn 3.0 <210> 1 <211> 22 <212> DNA <213> Artificial Sequence <220> <223> IL-4_F primer <400> 1 cagggtgctt cgcaaatttt ac 22 <210> 2 <211> 21 <212> DNA <213> Artificial Sequence <220> <223> IL-4_R primer <400> 2 accgagaacc ccagacttgt t 21 <210> 3 <211> 20 <212> DNA <213> Artificial Sequence <220> IL-13_F primer <400> 3 ggtggcctca cctccccaag 20 <210> 4 <211> 25 <212> DNA <213> Artificial Sequence <220> <223> IL-13_R primer <400> 4 gatgacactg cagttggaga tgctg 25 <210> 5 <211> 21 <212> DNA <213> Artificial Sequence <220> <223> TNF-alpha_F primer <400> 5 cagccgattt gccacttcat a 21 <210> 6 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> TNF-alpha_R primer <400> 6 tccttagggc aagggctctt 20 <210> 7 <211> 21 <212> DNA <213> Artificial Sequence <220> <223> IL-1beta_F primer <400> 7 ttacagtggc aatgaggatg a 21 <210> 8 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> IL-1beta_R primer <400> 8 tgtagtggtg gtcggagatt 20 <210> 9 <211> 26 <212> DNA <213> Artificial Sequence <220> <223> IL-6_F primer <400> 9 cctgagaaag gagacatgta acaaga 26 <210> 10 <211> 23 <212> DNA <213> Artificial Sequence <220> <223> IL-6_R primer <400> 10 tggaaggttc aggttgtttt ctg 23 <210> 11 <211> 18 <212> DNA <213> Artificial Sequence <220> <223> IL-8_F primer <400> 11 ctggccgtgg ctctcttg 18 <210> 12 <211> 22 <212> DNA <213> Artificial Sequence <220> <223> IL-8_R primer <400> 12 ttagcactcc ttggcaaaac tg 22 <210> 13 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> beta-actin_F primer <400> 13 accgtgaaaa gatgacccag 20 <210> 14 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> beta-actin_R primer <400> 14 tgtcagctgt ggtggtgaag 20
Claims (7)
상기 알러지성 질환은 부종, 과민증(anaphylaxis), 알러지성 비염(allergic rhinitis), 천식(asthma), 알러지성 결막염(allergic conjunctivitis), 알러지성 피부염(allergic dermatitis), 접촉성 피부염, 두드러기, 소양증, 곤충 알러지, 식품 알러지 및 약품 알러지로 이루어진 군에서 선택되는 하나 이상을 포함하는 것을 특징으로 하는 알러지성 질환 또는 아토피 피부염의 예방 또는 치료용 약학적 조성물.
As a pharmaceutical composition for the prevention or treatment of allergic diseases or atopic dermatitis comprising thiazole or a pharmaceutically acceptable salt thereof as an active ingredient,
The allergic diseases include edema, anaphylaxis, allergic rhinitis, asthma, allergic conjunctivitis, allergic dermatitis, contact dermatitis, hives, pruritus, insects A pharmaceutical composition for the prevention or treatment of allergic diseases or atopic dermatitis, characterized in that it comprises at least one selected from the group consisting of allergy, food allergy and drug allergy.
상기 유효성분은 IL-4, IL-13, TNF-α, IL-1β, IL-6 또는 IL-8의 발현을 감소시키거나, 히스타민의 분비량을 감소시키는 것을 특징으로 하는 알러지성 질환 또는 아토피 피부염의 예방 또는 치료용 약학적 조성물.
The method of claim 1,
The active ingredient is an allergic disease or atopic dermatitis, characterized by reducing the expression of IL-4, IL-13, TNF-α, IL-1β, IL-6 or IL-8, or reducing the amount of histamine Pharmaceutical composition for the prophylaxis or treatment of.
상기 알러지성 질환은 부종, 과민증(anaphylaxis), 알러지성 비염(allergic rhinitis), 천식(asthma), 알러지성 결막염(allergic conjunctivitis), 알러지성 피부염(allergic dermatitis), 접촉성 피부염, 두드러기, 소양증, 곤충 알러지, 식품 알러지 및 약품 알러지로 이루어진 군에서 선택되는 하나 이상을 포함하는 것을 특징으로 하는 알러지성 질환 또는 아토피 피부염의 예방 또는 개선용 의약외품 조성물.
As a quasi-drug composition for the prevention or improvement of allergic diseases or atopic dermatitis comprising thiazole or a pharmaceutically acceptable salt thereof as an active ingredient,
The allergic diseases include edema, anaphylaxis, allergic rhinitis, asthma, allergic conjunctivitis, allergic dermatitis, contact dermatitis, hives, pruritus, insects A quasi-drug composition for the prevention or improvement of allergic diseases or atopic dermatitis, characterized in that it comprises at least one selected from the group consisting of allergy, food allergy and drug allergy.
상기 알러지성 질환은 부종, 과민증(anaphylaxis), 알러지성 비염(allergic rhinitis), 천식(asthma), 알러지성 결막염(allergic conjunctivitis), 알러지성 피부염(allergic dermatitis), 접촉성 피부염, 두드러기, 소양증, 곤충 알러지, 식품 알러지 및 약품 알러지로 이루어진 군에서 선택되는 하나 이상을 포함하는 것을 특징으로 하는 알러지성 질환 또는 아토피 피부염의 예방 또는 개선용 화장료 조성물.
As a cosmetic composition for the prevention or improvement of allergic diseases or atopic dermatitis comprising thiazole or a cosmetically acceptable salt thereof as an active ingredient,
The allergic diseases include edema, anaphylaxis, allergic rhinitis, asthma, allergic conjunctivitis, allergic dermatitis, contact dermatitis, hives, pruritus, insects Cosmetic composition for the prevention or improvement of allergic diseases or atopic dermatitis, characterized in that it comprises at least one selected from the group consisting of allergy, food allergy and drug allergy.
상기 알러지성 질환은 부종, 과민증(anaphylaxis), 알러지성 비염(allergic rhinitis), 천식(asthma), 알러지성 결막염(allergic conjunctivitis), 알러지성 피부염(allergic dermatitis), 접촉성 피부염, 두드러기, 소양증, 곤충 알러지, 식품 알러지 및 약품 알러지로 이루어진 군에서 선택되는 하나 이상을 포함하는 것을 특징으로 하는 알러지성 질환 또는 아토피 피부염의 예방 또는 개선용 향료 조성물.
As a fragrance composition for the prevention or improvement of allergic diseases or atopic dermatitis, including thiazole or a cosmetically acceptable salt thereof as an active ingredient,
The allergic diseases include edema, anaphylaxis, allergic rhinitis, asthma, allergic conjunctivitis, allergic dermatitis, contact dermatitis, hives, pruritus, insects Perfume composition for the prevention or improvement of allergic diseases or atopic dermatitis, characterized in that it comprises at least one selected from the group consisting of allergy, food allergy and drug allergy.
상기 알러지성 질환은 부종, 과민증(anaphylaxis), 알러지성 비염(allergic rhinitis), 천식(asthma), 알러지성 결막염(allergic conjunctivitis), 알러지성 피부염(allergic dermatitis), 접촉성 피부염, 두드러기, 소양증, 곤충 알러지, 식품 알러지 및 약품 알러지로 이루어진 군에서 선택되는 하나 이상을 포함하는 것을 특징으로 하는 알러지성 질환 또는 아토피 피부염의 예방 또는 개선용 건강기능식품 조성물.As a health functional food composition for the prevention or improvement of allergic diseases or atopic dermatitis comprising thiazole or a food acceptable salt thereof as an active ingredient,
The allergic diseases include edema, anaphylaxis, allergic rhinitis, asthma, allergic conjunctivitis, allergic dermatitis, contact dermatitis, hives, pruritus, insects Functional food composition for the prevention or improvement of allergic diseases or atopic dermatitis, characterized in that it comprises at least one selected from the group consisting of allergy, food allergy and drug allergy.
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PCT/KR2020/010654 WO2021029659A1 (en) | 2019-08-12 | 2020-08-12 | Composition for preventing or treating allergic diseases or atopic dermatitis comprising ethyl vanillin, suberic acid, thiazole or salt thereof as effective component |
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