WO2023018273A1 - Composition for prevention, alleviation, or treatment of pigment disease - Google Patents
Composition for prevention, alleviation, or treatment of pigment disease Download PDFInfo
- Publication number
- WO2023018273A1 WO2023018273A1 PCT/KR2022/012075 KR2022012075W WO2023018273A1 WO 2023018273 A1 WO2023018273 A1 WO 2023018273A1 KR 2022012075 W KR2022012075 W KR 2022012075W WO 2023018273 A1 WO2023018273 A1 WO 2023018273A1
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- WO
- WIPO (PCT)
- Prior art keywords
- nevus
- pigmented
- composition
- pigmentation
- melanoma
- Prior art date
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Images
Classifications
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- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- 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
- A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
- A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
- A61K31/365—Lactones
- A61K31/366—Lactones having six-membered rings, e.g. delta-lactones
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
- A61K8/49—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
- A61Q19/00—Preparations for care of the skin
- A61Q19/02—Preparations for care of the skin for chemically bleaching or whitening the skin
Abstract
The present invention relates to a composition for prevention, alleviation, or treatment of a pigment disease and, more specifically, to a composition comprising 7-desacetoxy-6,7-dehydrogedunin (7DG) or a pharmaceutically or cosmetically acceptable salt thereof as an active ingredient for prevention, alleviation, or treatment of a pigment disease. When utilized, the composition of the present invention can more effectively prevent, alleviate, or treat various pigment diseases attributed to pigmentation.
Description
본 발명은 색소 질환의 예방, 개선 또는 치료용 조성물에 관한 것으로, 보다 상세하게는 색소 침착(pigmentation)에 기인한 다양한 색소 질환을 예방 또는 치료할 수 있는 조성물에 관한 것이다.The present invention relates to a composition for preventing, improving or treating pigment diseases, and more particularly, to a composition capable of preventing or treating various pigment diseases caused by pigmentation.
인간 피부는 다양한 외부 환경적 스트레스에 노출되는 장기로, 자외선(UVR) 등에 의한 잠재적 손상을 방어하기 위하여 다양한 메커니즘이 존재한다. 이러한 방어 메커니즘으로는 DNA 손상 메커니즘, 카탈레이즈 및 과산화물 제거효소와 같은 다양한 효소, 및 피부 색소 침착을 포함한다. 이러한 요소 중에는, 색소 침착이 가장 중요한 광-보호적인 요소에 해당한다. 타이로시나아제 효소(tyrosinase)는 멜라닌 색소의 합성 경로에서 두가지의 속도 제한적인 반응을 촉진시키므로 색소 침착에 중요한 조절자로 작용한다. 이러한 속도 제한적인 반응으로는 1) 3,4-디히드록시페닐알라닌(3,4-dihydroxyphenylalanine, DOPA)을 생성하기 위한 타이로신 히드록실화와, 2) 도파퀴논(dopaquinone)을 생성하기 위한 DOPA 산화 공정이 있다. 최근 멜라닌 합성 저해 효과 및 타이로시나아제(tyrosinase) 활성 저해 효과를 가지면서도 피부 자극이 없는 신규한 화합물이 개시된 바 있다(한국등록특허 제10-2273473호 참조).Human skin is an organ exposed to various external environmental stresses, and various mechanisms exist to protect against potential damage caused by ultraviolet (UVR) and the like. These defense mechanisms include DNA damage mechanisms, various enzymes such as catalase and peroxide scavenging enzymes, and skin pigmentation. Among these factors, pigmentation is the most important photo-protective factor. The enzyme tyrosinase acts as an important regulator of pigmentation by catalyzing two rate-limiting reactions in the synthesis pathway of melanin pigment. These rate-limiting reactions include 1) tyrosine hydroxylation to produce 3,4-dihydroxyphenylalanine (DOPA) and 2) DOPA oxidation to produce dopaquinone. there is Recently, a novel compound having melanin synthesis inhibitory effect and tyrosinase activity inhibitory effect without skin irritation has been disclosed (see Korean Patent Registration No. 10-2273473).
색소 침착은 기미(melasma), 검버섯(age spots) 및 일광성 각화증(solar keratosis) 등과 같은 질환을 유발하여, 화장품 업계에서 피부 색의 개선은 오래 전부터 요구되어 왔고, 다양한 미백 제품이 전세계적으로 판매되고 있다. 이러한 미백 제품 또는 치료제들은 하이드로퀴논, 레티노이드 및 타이로시네이즈 억제제 등을 포함하고 있는데, 이들은 돌연변이, 독성 및 조직 흑갈병(ochronosis, blue-black hyperpigmentation of skin) 등의 부작용이 문제되고 있는 실정이다. Pigmentation causes diseases such as melasma, age spots, and solar keratosis, and improvement of skin color has long been required in the cosmetics industry, and various whitening products are sold worldwide. It is becoming. These whitening products or treatments include hydroquinone, retinoids, and tyrosinase inhibitors, which are problematic in terms of side effects such as mutation, toxicity, and tissue blackening (ochronosis, blue-black hyperpigmentation of skin).
최근 이러한 제제들을 대신할 수 있는 부작용이 없으면서도 치료 효과가 뛰어난 약물을 개발하기 위하여 다양한 노력들이 시도되고 있다. 이에, 본 발명자들은 상기 목적을 달성하기 위하여 예의 노력한 결과, 색소 침착을 비롯한 다양한 색소 질환의 개선 또는 치료 효과가 뛰어나면서 독성이 없고 안전한 물질을 발굴하기에 이르렀다. Recently, various efforts have been made to develop drugs with excellent therapeutic effects without side effects that can replace these agents. Accordingly, the inventors of the present invention have made diligent efforts to achieve the above object, and have discovered a non-toxic and safe material that is excellent in improving or treating various pigment diseases including pigmentation.
본 발명의 일 목적은 멜라닌 형성 억제 효과가 뛰어나 색소 침착에 기인한 다양한 색소 질환을 예방, 개선 또는 치료할 수 있는 약학 조성물을 제공하는 것이다.One object of the present invention is to provide a pharmaceutical composition capable of preventing, improving or treating various pigment diseases caused by pigmentation with excellent melanin formation inhibitory effect.
본 발명의 다른 목적은 멜라닌 형성 억제 효과가 뛰어나 색소 침착에 기인한 다양한 색소 질환을 예방 또는 개선할 수 있는 식품 조성물을 제공하는 것이다.Another object of the present invention is to provide a food composition capable of preventing or improving various pigment diseases caused by pigmentation with excellent melanin formation inhibitory effect.
본 발명의 또 다른 목적은 멜라닌 형성 억제 효과가 뛰어나 색소 침착에 기인한 다양한 색소 질환을 예방 또는 개선할 수 있는 화장료 조성물을 제공하는 것이다.Another object of the present invention is to provide a cosmetic composition capable of preventing or improving various pigment diseases caused by pigmentation with excellent melanin formation inhibitory effect.
본 발명의 또 다른 목적은 멜라닌 형성 억제 효과가 뛰어나 색소 침착을 개선할 수 있는 미백용 조성물을 제공하는 것이다.Another object of the present invention is to provide a whitening composition capable of improving pigmentation with excellent melanin formation inhibitory effect.
본 발명의 또 다른 목적은 멜라닌 형성 억제 효과가 뛰어나 색소 침착에 기인한 다양한 색소 질환을 예방, 개선, 치료할 수 있는 방법을 제공하는 것이다.Another object of the present invention is to provide a method capable of preventing, improving, and treating various pigment diseases caused by pigmentation with excellent melanin formation inhibitory effect.
그러나 본 발명이 이루고자 하는 기술적 과제는 이상에서 언급한 과제에 제한되지 않으며, 언급되지 않은 또 다른 과제들은 아래의 기재로부터 당업계에서 통상의 지식을 가진 자에게 명확하게 이해될 수 있을 것이다.However, the technical problem to be achieved by the present invention is not limited to the above-mentioned problems, and other problems not mentioned will be clearly understood by those skilled in the art from the following description.
이하, 본원에 기재된 다양한 구체예가 도면을 참조로 기재된다. 하기 설명에서, 본 발명의 완전한 이해를 위해서, 다양한 특이적 상세사항, 예컨대, 특이적 형태, 조성물 및 공정 등이 기재되어 있다. 그러나, 특정의 구체예는 이들 특이적 상세 사항 중 하나 이상 없이, 또는 다른 공지된 방법 및 형태와 함께 실행될 수 있다. 다른 예에서, 공지된 공정 및 제조 기술은 본 발명을 불필요하게 모호하게 하지 않게 하기 위해서, 특정의 상세사항으로 기재되지 않는다. "한 가지 구체예" 또는 "구체예"에 대한 본 명세서 전체를 통한 참조는 구체예와 결부되어 기재된 특별한 특징, 형태, 조성 또는 특성이 본 발명의 하나 이상의 구체예에 포함됨을 의미한다. 따라서, 본 명세서 전체에 걸친 다양한 위치에서 표현된 "한 가지 구체예에서" 또는 "구체예"의 상황은 반드시 본 발명의 동일한 구체예를 나타내지는 않는다. 추가로, 특별한 특징, 형태, 조성, 또는 특성은 하나 이상의 구체예에서 어떠한 적합한 방법으로 조합될 수 있다.Hereinafter, various embodiments described herein are described with reference to the drawings. In the following description, numerous specific details are set forth, such as specific forms, compositions and processes, etc., in order to provide a thorough understanding of the present invention. However, certain embodiments may be practiced without one or more of these specific details, or with other known methods and forms. In other instances, well known processes and manufacturing techniques have not been described in specific detail in order not to unnecessarily obscure the present invention. Reference throughout this specification to “one embodiment” or “an embodiment” means that a particular feature, form, composition or characteristic described in connection with the embodiment is included in one or more embodiments of the invention. Thus, the appearances of "in one embodiment" or "an embodiment" in various places throughout this specification do not necessarily refer to the same embodiment of the invention. Additionally, particular features, forms, compositions, or properties may be combined in one or more embodiments in any suitable way.
본 발명 내 특별한 정의가 없으면 본 명세서에 사용된 모든 과학적 및 기술적인 용어는 본 발명이 속하는 기술분야에서 당업자에 의하여 통상적으로 이해되는 것과 동일한 의미를 가진다.Unless there is a specific definition within the present invention, all scientific and technical terms used herein have the same meaning as commonly understood by a person skilled in the art to which the present invention belongs.
본 발명의 일 구현 예에 따르면, 하기 화학식 1로 표시되는 7-데스아세톡시-6,7-디하이드로게두닌 (7-Desacetoxy-6,7-dehydrogedunin; 7DG) 또는 이의 약제학적으로 허용 가능한 염을 유효 성분으로 포함하는, 색소 질환의 예방 또는 치료용 약학 조성물에 관한 것이다:According to one embodiment of the present invention, 7-desacetoxy-6,7-dehydrogedunin represented by Formula 1 below (7-Desacetoxy-6,7-dehydrogedunin; 7DG) or a pharmaceutically acceptable salt thereof It relates to a pharmaceutical composition for preventing or treating pigment diseases, comprising as an active ingredient:
[화학식 1][Formula 1]
본 발명에서 7-데스아세톡시-6,7-디하이드로게두닌 (7-Desacetoxy-6,7-dehydrogedunin; 7DG)은 단백질 키나제 R (Double-stranded RNA-dependent protein kinase; PKR)의 C-말단과 직접 상호 작용하는 단백질 키나제 R의 선택적 억제제(CAS 번호: 26927-01-5)이다. PKR을 직접 표적으로 하는 세포 투과성 게두닌 유사체는 가역적 상호 작용을 통해 인플라마솜/피롭토솜(inflammasome/pyroptosome)과 같은 PKR 신호 전달 복합체 어셈블리를 방해하여 PKR 매개 세포 작용을 억제하는 효과가 있는 것으로 알려져 있다.In the present invention, 7-Desacetoxy-6,7-dehydrogedunin (7-Desacetoxy-6,7-dehydrogedunin; 7DG) is the C-terminus of protein kinase R (Double-stranded RNA-dependent protein kinase; PKR) It is a selective inhibitor of protein kinase R (CAS number: 26927-01-5) that interacts directly with Cell-permeable gedunin analogues that directly target PKR are known to have the effect of inhibiting PKR-mediated cellular actions by interfering with the assembly of PKR signaling complexes such as inflammasome/pyroptosome through reversible interactions. there is.
본 발명에서 상기 약제학적으로 허용 가능한 염은 산 또는 염기의 부가염을 포함할 수 있다. 예를 들면, 상기 화합물은 유기산 또는 무기산의 부가염의 형태로 있을 수 있다. 염은 환자에 투여되었을 때에 환자에서 바람직한 효과를 갖는 것으로, 그들의 모화합물의 활성을 유지하는 임의의 염들을 포함하지만, 이에 특별히 한정되는 것은 아닐 수 있다. 이러한 염들은 무기염 및 유기염, 예컨대 아세트산, 질산, 아스파트산, 술폰산, 설퓨릭산, 말레산, 글루탐산, 포름산, 숙신산, 인산, 프탈산, 탄닌산, 타르타르산, 히드로브롬산, 프로피온산, 벤젠술폰산, 벤조산, 스테아르산, 락트산, 비카르본산, 비설퓨릭산, 비타르타르산, 옥살산, 부틸산, 칼슘 이데트, 카르보닉산, 클로로벤조산, 시트르산, 이데트산, 톨루엔술폰산, 푸마르산, 글루셉트산, 에실린산, 파모익산, 글루코닉산, 메틸질산, 말론산, 염산, 히드로요도익산, 히드록시나프톨산, 이세티온산, 락토비오닉산, 만델산, 점액산, 나프실릭산, 뮤코닉산, p-니트로메탄술폰산, 헥사믹산, 판토테닉산, 모노히드로겐인산, 디히드로겐인산, 살리실산, 술파민산, 술파닐린산, 메탄술폰산의 염 등을 포함할 수 있다. 염기의 부가염은 알칼리 금속 또는 알칼리 토금속의 염, 예컨대 암모늄, 리튬, 나트륨, 칼륨, 마그네슘, 칼슘 등의 염; 유기 염기를 갖는 염, 예컨대 벤자틴, N-메틸-D-글루카민, 하이드라바민 등의 염; 및 아미노산을 갖는 염, 예컨대 아르기닌, 리신 등을 포함할 수 있다. 또한, 이들 염들은 적정 염기 또는 산으로 처리함으로써 유리된 형태로 전환될 수 있다.In the present invention, the pharmaceutically acceptable salt may include an acid or base addition salt. For example, the compounds may be in the form of addition salts of organic or inorganic acids. Salts have desirable effects on patients when administered to patients, and include any salts that retain the activity of their parent compound, but may not be particularly limited thereto. These salts include inorganic and organic salts such as acetic acid, nitric acid, aspartic acid, sulfonic acid, sulfuric acid, maleic acid, glutamic acid, formic acid, succinic acid, phosphoric acid, phthalic acid, tannic acid, tartaric acid, hydrobromic acid, propionic acid, benzenesulfonic acid, Benzoic acid, stearic acid, lactic acid, bicarboxylic acid, bisulfuric acid, bitartaric acid, oxalic acid, butyric acid, calcium idete, carbonic acid, chlorobenzoic acid, citric acid, idetic acid, toluenesulfonic acid, fumaric acid, gluseptic acid, ecilin Acid, pamoic acid, gluconic acid, methyl nitric acid, malonic acid, hydrochloric acid, hydroiodoic acid, hydroxynaphtholic acid, isethionic acid, lactobionic acid, mandelic acid, mucoic acid, napsylic acid, muconic acid, p -It may include salts of nitromethanesulfonic acid, hexamic acid, pantothenic acid, monohydrogenphosphoric acid, dihydrogenphosphoric acid, salicylic acid, sulfamic acid, sulfanilic acid, methanesulfonic acid, and the like. Addition salts of bases include salts of alkali metals or alkaline earth metals, such as salts of ammonium, lithium, sodium, potassium, magnesium, calcium and the like; salts with organic bases such as benzathine, N-methyl-D-glucamine, hydrabamine and the like; and salts with amino acids such as arginine, lysine, and the like. Also, these salts can be converted to the free form by treatment with an appropriate base or acid.
본 발명에서 상기 색소 질환이란 멜라닌 합성 과정에서 조절 장애가 발생하면 초래되는 질환으로 색소 침착(pigmentation)에 의한 질환일 수 있으며, 보다 구체적으로 과색소 침착(hyperpigmentation)에 의한 질환일 수 있다. 포유동물의 피부, 머리 및 눈 등에서 시각적 색깔은 멜라노솜(melanosomes)의 양, 질 및 상피세포의 분포에 기인하는데, 상기 멜라노솜은 특별한 수지 세포 중 하나인 멜라닌 세포(melanocyte)에 의하여 형성된다. 멜라닌 색소는 멜라노솜에서 합성되어 멜라닌 세포의 수상 돌기에 의하여 케라틴 세포(keratinocytes)로 이동하고, 멜라닌의 분포 패턴이 피부 색깔을 결정하게 된다. 멜라닌 색소는 태양 UV 방사선으로부터 넓은 파장 범위로 피부를 보호하고, 피부에서 생산되는 자유 라디칼을 흡수하는 기능을 하고, 멜라닌 형성에 관련된 효소의 발현에 의하여 멜라닌 합성이 조절된다. 이러한 멜라닌 합성 조절에 문제가 발생하는 질환을 색소 질환이라 한다.In the present invention, the pigment disease is a disease caused by dysregulation in the melanin synthesis process, and may be a disease caused by pigmentation, and more specifically, a disease caused by hyperpigmentation. Visual color in mammalian skin, head and eyes is due to the quantity and quality of melanosomes and the distribution of epithelial cells. The melanosomes are formed by melanocytes, one of special resin cells. Melanin pigment is synthesized in melanosomes and moves to keratinocytes by dendrites of melanocytes, and the distribution pattern of melanin determines skin color. Melanin pigment protects the skin from solar UV radiation in a wide wavelength range, functions to absorb free radicals produced in the skin, and melanin synthesis is regulated by the expression of enzymes related to melanin formation. A disease in which a problem occurs in the regulation of melanin synthesis is called a pigment disease.
본 발명에서 상기 멜라닌(melanin)은 피부, 털, 눈의 맥락막 등에 있는 페놀화합물의 산화 중합에 의하여 생성되는 흑갈색의 색소로 멜라닌 세포 (melanocyte)에서 생성된다. 동물의 경우 피부 등에 분포하는 멜라노사이트라고 하는 세포에서 타이로시나아제에 의한 타이로신의 산화에 의해 생성된다. 태양광선에 노출시 멜라닌이 형성되는데 멜라닌 형성 세포의 종류와 양에 따라 피부 색깔이 달라지게 된다. 멜라닌은 태양광선의 자외선에 대한 피부 보호 작용을 하는 것으로도 알려져 있다. 그 예로 피부 색깔이 검은 사람은 피부색이 옅은 사람에 비하여 멜라닌 색소가 더 많이 형성되어 태양광선에 노출시 자외선으로부터 화상을 덜 입게 되는 것으로 알려져 있다. 또한, 멜라닌은 피부색을 결정짓는 가장 중요한 요소이다. 정상 인체의 피부색은 멜라닌 소체의 크기, 모양, 유형, 색 분포에 의해 결정된다. 색소 침착을 조절함에 있어서 100 개 이상의 단백질이 관여한다. 예를 들어, 멜라닌 합성은 타이로신(tyrosine)의 도파퀴논(dopaquinone)으로 산화되면서 개시되는데, 상기 산화 과정은 타이로시나아제 효소에 의하여 촉매화된다. 도파퀴논은 이후 분자 내 고리화 반응 및 중합 반응에 의하여 유멜라닌(eumelanin)으로 전환된다. 상기한 멜라닌 합성 과정에서 조절 장애가 발생하면 이는 색소의 과다한 침착(hyperpigmentation) 혹은 저색소 침착(hypopigmentation)을 초래하게 된다.In the present invention, the melanin (melanin) is a dark brown pigment produced by oxidative polymerization of phenolic compounds in the skin, hair, choroid of the eye, etc., and is produced in melanocytes. In the case of animals, it is produced by oxidation of tyrosine by tyrosinase in cells called melanocytes distributed on the skin. When exposed to sunlight, melanin is formed, and the color of the skin changes depending on the type and amount of melanin-forming cells. Melanin is also known to protect the skin from ultraviolet rays of the sun's rays. For example, it is known that dark-skinned people have more melanin pigment than light-skinned people, so they are less likely to get burned from ultraviolet rays when exposed to sunlight. In addition, melanin is the most important factor determining skin color. Normal human skin color is determined by the size, shape, type, and color distribution of melanocytes. More than 100 proteins are involved in regulating pigmentation. For example, melanin synthesis is initiated by the oxidation of tyrosine to dopaquinone, which is catalyzed by the enzyme tyrosinase. Dopaquinone is then converted to eumelanin by intramolecular cyclization and polymerization. When dysregulation occurs in the melanin synthesis process, it causes hyperpigmentation or hypopigmentation of pigment.
본 발명에서 멜라닌 합성(melanogenesis)은 o-디페놀류의 산화적 중합에 의해 멜라닌이 생성되는 과정을 말한다. 동식물계와 균계에 널리 분포하며, 특히 척추동물에서 멜라닌은 멜라닌세포 또는 흑색소포의 세포질 내의 멜라닌소체에서 타이로신이 타이로시나아제 (카테콜산화효소)에 의한 산화에 의해 생성되며, 상기에서 생성된 멜라닌은 피부를 암색화시키게 된다. In the present invention, melanogenesis refers to a process in which melanin is produced by oxidative polymerization of o-diphenols. Widely distributed in animal and plant kingdoms and fungi, especially in vertebrates, melanin is produced by oxidation of tyrosine by tyrosinase (catechol oxidase) in melanocytes or melanosomes in the cytoplasm of melanocytes. Melanin darkens the skin.
본 발명의 조성물은 멜라닌 합성을 억제하거나 멜라닌 합성량을 감소시켜 색소 침착에 기인한 색소 질환을 효과적으로 예방, 개선 또는 치료할 수 있다.The composition of the present invention can effectively prevent, improve, or treat pigment diseases caused by pigmentation by suppressing melanin synthesis or reducing the amount of melanin synthesis.
본 발명에서 상기 색소 질환은 색소 침착에 기인한 질환으로, 피부 또는 손발톱의 특정 부위에서 멜라닌의 과도한 증가에 의해 다른 부위에 비해 검거나 어둡게 되는 질환을 의미할 수 있고, 보다 광범위하게는 염증 후 색소 침착이 유발되어 발생하는 질환을 포함하는 것으로 정의한다. 바람직하게는 상기 색소 질환은 기미, 주근깨, 검버섯, 잡티, 노인성 색소반, 표피 멜라닌세포성 병변(Epidermal melanocytic lesion), 밀크커피 반점(Cafe's au lait macules), 모반, 베커 모반(Becker's Nevus), 반문상 모반(Nevus Spilus), 흑자(Lentigines), 흑색점, 진피 멜라닌세포성 병변(Dermal melanocytic lesions), 몽고반(Mongolian spot), 오타 모반(Nevus of Ota), 후천성 양측성 오타 모반양 반(Acquired bilateral nevus of Ota-like macules), 이토 모반(Nevus of Ito), 청색 모반(Blue nevus), 멜라닌형성세포성 모반(Melanocytic nevus), 경계 모반(Junctional nevus), 복합 모반(Compound nevus), 진피내 모반(Intradermal nevus), 운륜 모반(Halo nevus), 선천성 멜라닌세포성 모반(Congenital nevocytic nevus), 스피츠 모반(Spitz nevus), 이형성 모반(Dysplastic nevus), 임신성 갈색반(gravidic chloasma), 흑색종(Melanoma), 악성 흑자 흑색종(Lentigo maligna melanoma), 표재 확장성 흑색종(Superficial spreading melanoma), 선단 흑자성 흑색종(Acral lentiginous melanoma), 결절성 흑색종(Nodular melanoma), 색소성 기저세포암(pigment basal cell carcinoma), 색소성 피부섬유종(dermatofibromas), 색소성 피부낭종(dermoid cyst), 색소성 켈로이드(keloid), 일광 흑색증(solar lentigines), 색소성 편평태선(Lichen planus), 색소성 접촉피부염(Contact dermatitis), 자외선에 의한 색소 침착, 약물에 의한 색소 침착, 상처로 인한 색소 침착, 염증 후 색소 침착, 색소성 각질가시세포종(keratoacanthomas) 및 릴 흑피증(Riehl's melanosis) 등이 있으나, 이에 한정되는 것은 아니다.In the present invention, the pigment disease is a disease caused by pigmentation, and may mean a disease in which a specific part of the skin or nail becomes black or dark compared to other parts due to an excessive increase in melanin, and more broadly, post-inflammatory pigmentation. It is defined as including diseases caused by deposition. Preferably, the pigment disease is chloasma, freckles, age spots, blemishes, senile pigment spots, epidermal melanocytic lesions, milk coffee spots (Cafe's au lait macules), nevus, Becker's nevus, spots Nevus Spilus, Lentigines, lentigo, Dermal melanocytic lesions, Mongolian spot, Nevus of Ota, Acquired bilateral nevus of Ota nevus of Ota-like macules, Nevus of Ito, blue nevus, melanocytic nevus, junctional nevus, compound nevus, intradermal nevus Intradermal nevus, Halo nevus, Congenital nevocytic nevus, Spitz nevus, Dysplastic nevus, Gravidic chloasma, Melanoma , Lentigo maligna melanoma, superficial spreading melanoma, acral lentiginous melanoma, nodular melanoma, pigment basal cell carcinoma carcinoma), dermatofibromas, pigmented dermoid cyst, pigmented keloid, solar lentigines, lichen planus pigmented, contact dermatitis pigmented dermatitis), pigmentation by UV rays, drug-induced Pigmentation, pigmentation due to wounds, post-inflammatory pigmentation, keratoacanthomas, and Riehl's melanosis, but are not limited thereto.
본 발명에서 "예방"은 본 발명의 약학 조성물을 이용하여 색소 침착에 기인한 색소 질환의 증상을 차단하거나, 그 증상의 억제 또는 지연시키는 모든 행위라면 제한없이 포함할 수 있다. In the present invention, "prevention" may include without limitation any act of blocking, suppressing or delaying the symptoms of a pigmentation disease caused by pigmentation by using the pharmaceutical composition of the present invention.
또한, 본 발명에서 "치료"는 본 발명의 약학 조성물을 이용하여 색소 침착에 기인한 색소 질환의 증상이 호전되거나 이롭게 되는 모든 행위라면 제한없이 포함할 수 있다. In addition, in the present invention, "treatment" may include without limitation any action that improves or benefits the symptoms of pigmentation diseases caused by pigmentation by using the pharmaceutical composition of the present invention.
본 발명에 있어서, 상기 약학 조성물은 캡슐, 정제, 과립, 주사제, 연고제, 분말 또는 음료 형태임을 특징으로 할 수 있으며, 상기 약학 조성물은 인간을 대상으로 하는 것을 특징으로 할 수 있다. In the present invention, the pharmaceutical composition may be in the form of capsules, tablets, granules, injections, ointments, powders or beverages, and the pharmaceutical composition may be intended for humans.
본 발명의 약학 조성물은 이들로 한정되는 것은 아니지만, 각각 통상의 방법에 따라 산제, 과립제, 캡슐, 정제, 수성 현탁액 등의 경구형 제형, 외용제, 좌제 및 멸균 주사용액의 형태로 제형화하여 사용될 수 있다. 본 발명의 약학 조성물은 약제적으로 허용 가능한 담체를 포함할 수 있다. 약제학적으로 허용되는 담체는 경구 투여 시에는 결합제, 활탁제, 붕해제, 부형제, 가용화제, 분산제, 안정화제, 현탁화제, 색소, 향료 등을 사용할 수 있으며, 주사제의 경우에는 완충제, 보존제, 무통화제, 가용화제, 등장제, 안정화제 등을 혼합하여 사용할 수 있으며, 국소투여용의 경우에는 기제, 부형제, 윤활제, 보존제 등을 사용할 수 있다. 본 발명의 약제학적 조성물의 제형은 상술한 바와 같은 약제학적으로 허용되는 담체와 혼합하여 다양하게 제조될 수 있다. 예를 들어, 경구 투여시에는 정제, 트로키, 캡슐, 엘릭서(elixir), 서스펜션, 시럽, 웨이퍼 등의 형태로 제조할 수 있으며, 주사제의 경우에는 단위 투약 앰플 또는 다수회 투약 형태로 제조할 수 있다. 기타, 용액, 현탁액, 정제, 캡슐, 서방형 제제 등으로 제형할 수 있다.The pharmaceutical composition of the present invention is not limited thereto, but may be formulated and used in the form of oral formulations such as powders, granules, capsules, tablets, aqueous suspensions, external preparations, suppositories and sterile injection solutions according to conventional methods, respectively. there is. The pharmaceutical composition of the present invention may include a pharmaceutically acceptable carrier. Pharmaceutically acceptable carriers may include binders, lubricants, disintegrants, excipients, solubilizers, dispersants, stabilizers, suspending agents, pigments, flavors, etc. for oral administration, and buffers, preservatives, and painless agents for injections. A topical, solubilizing agent, isotonic agent, stabilizer, etc. may be mixed and used, and in the case of topical administration, a base, excipient, lubricant, preservative, etc. may be used. The dosage form of the pharmaceutical composition of the present invention may be variously prepared by mixing with a pharmaceutically acceptable carrier as described above. For example, for oral administration, it can be prepared in the form of tablets, troches, capsules, elixirs, suspensions, syrups, wafers, etc., and in the case of injections, it can be prepared in unit dosage ampoules or multiple dosage forms. there is. In addition, it may be formulated into solutions, suspensions, tablets, capsules, sustained-release preparations, and the like.
한편, 제제화에 적합한 담체, 부형제 및 희석제의 예로는, 락토즈, 덱스트로즈, 수크로즈, 솔비톨, 만니톨, 자일리톨, 에리스리톨, 말디톨, 전분, 아카시아 고무, 알지네이트, 젤라틴, 칼슘 포스페이트, 칼슘 실리케이트, 셀룰로즈, 메틸 셀룰로즈, 미정질 셀룰로즈, 폴리비닐피롤리돈, 물, 메틸하이드록시벤조에이트, 프로필하이드록시벤조에이트, 탈크, 마그네슘 스테아레이트 또는 광물유 등이 사용될 수 있다. 또한, 충진제, 항응집제, 윤활제, 습윤제, 향료, 유화제, 방부제 등을 추가로 포함할 수 있다.On the other hand, examples of carriers, excipients and diluents suitable for formulation include lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, malditol, starch, acacia gum, alginate, gelatin, calcium phosphate, calcium silicate, Cellulose, methyl cellulose, microcrystalline cellulose, polyvinylpyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate or mineral oil and the like can be used. In addition, fillers, anti-coagulants, lubricants, wetting agents, flavoring agents, emulsifiers, preservatives, and the like may be further included.
본 발명에 따른 약학 조성물의 투여 경로는 이들로 한정되는 것은 아니지만 구강, 정맥내, 근육내, 동맥내, 골수내, 경막내, 심장내, 경피, 피하, 복강내, 비강내, 장관, 국소, 설하 또는 직장이 포함된다. 경구 또는 비경구 투하가 바람직하다. The route of administration of the pharmaceutical composition according to the present invention is not limited to these, but is oral, intravenous, intramuscular, intraarterial, intramedullary, intrathecal, intracardiac, transdermal, subcutaneous, intraperitoneal, intranasal, intestinal, topical, This includes sublingual or rectal. Oral or parenteral administration is preferred.
본 발명에서, "비경구"는 피하, 피내, 정맥내, 근육내, 관절내, 활액낭내, 흉골내, 경막내, 병소내 및 두개골내 주사 또는 주입기술을 포함한다. 본 발명의 약학 조성물은 또한 직장 투여를 위한 좌제의 형태로 투여될 수 있다.In the present invention, "parenteral" includes subcutaneous, intradermal, intravenous, intramuscular, intraarticular, intracapsular, intrasternal, intrathecal, intralesional and intracranial injection or infusion techniques. The pharmaceutical composition of the present invention may also be administered in the form of a suppository for rectal administration.
본 발명의 약학 조성물은 사용된 특정 화합물의 활성, 연령, 체중, 일반적인 건강, 성별, 정식, 투여시간, 투여경로, 배출율, 약물 배합 및 예방 또는 치료될 특정 질환의 중증을 포함한 여러 요인에 따라 다양하게 변할 수 있고, 상기 약학 조성물의 투여량은 환자의 상태, 체중, 질병의 정도, 약물 형태, 투여경로 및 기간에 따라 다르지만 당업자에 의해 적절하게 선택될 수 있고, 1일 0.0001 내지 50mg/kg 또는 0.001 내지 50mg/kg으로 투여할 수 있다. 투여는 하루에 한번 투여할 수도 있고, 수회 나누어 투여할 수도 있다. 상기 투여량은 어떠한 면으로든 본 발명의 범위를 한정하는 것은 아니다. 본 발명에 따른 의약 조성물은 환제, 당의정, 캡슐, 액제, 겔, 시럽, 슬러리, 현탁제로 제형될 수 있다.The pharmaceutical composition of the present invention varies depending on various factors including the activity of the specific compound used, age, body weight, general health, sex, diet, administration time, route of administration, excretion rate, drug combination and severity of the specific disease to be prevented or treated. The dosage of the pharmaceutical composition may vary depending on the patient's condition, weight, disease severity, drug form, administration route and period, but may be appropriately selected by those skilled in the art, and may be 0.0001 to 50 mg/kg per day or It can be administered at 0.001 to 50 mg/kg. Administration may be administered once a day, or may be administered in several divided doses. The dosage is not intended to limit the scope of the present invention in any way. The pharmaceutical composition according to the present invention may be formulated into a pill, dragee, capsule, liquid, gel, syrup, slurry, or suspension.
본 발명의 다른 구현 예에 따르면, 본 발명의 일 구현 예에 따르면, 하기 화학식 1로 표시되는 7-데스아세톡시-6,7-디하이드로게두닌 (7-Desacetoxy-6,7-dehydrogedunin; 7DG) 또는 이의 약제학적으로 허용 가능한 염을 유효 성분으로 포함하는, 색소 질환의 예방 또는 개선용 식품 조성물에 관한 것이다:According to another embodiment of the present invention, according to one embodiment of the present invention, 7-desacetoxy-6,7-dehydrogedunin represented by Formula 1 (7-Desacetoxy-6,7-dehydrogedunin; 7DG ) or a pharmaceutically acceptable salt thereof as an active ingredient, to a food composition for preventing or improving pigment diseases:
[화학식 1][Formula 1]
본 발명의 식품 조성물에서 7-데스아세톡시-6,7-디하이드로게두닌 (7-Desacetoxy-6,7-dehydrogedunin; 7DG) 화합물, 약제학적으로 허용가능한 염, 색소 질환 등에 관한 기재는 상기 색소 질환의 예방 또는 치료용 조성물에서 기재한 바와 동일하여, 본 명세서의 과도한 복잡성을 피하기 위하여 생략한다.In the food composition of the present invention, descriptions of 7-Desacetoxy-6,7-dehydrogedunin (7-Desacetoxy-6,7-dehydrogedunin; 7DG) compounds, pharmaceutically acceptable salts, pigment diseases, etc. Since it is the same as described in the composition for preventing or treating a disease, it is omitted in order to avoid excessive complexity of the present specification.
본 발명의 식품 조성물은 멜라닌 합성을 억제하거나 멜라닌 합성량을 감소시켜 색소 침착에 기인한 색소 질환을 효과적으로 예방 또는 개선할 수 있다.The food composition of the present invention can effectively prevent or improve pigment diseases caused by pigmentation by inhibiting melanin synthesis or reducing the amount of melanin synthesis.
본 발명에서 상기 색소 질환은 색소 침착에 기인한 질환으로, 바람직하게는 기미, 주근깨, 검버섯, 잡티, 노인성 색소반, 표피 멜라닌세포성 병변(Epidermal melanocytic lesion), 밀크커피 반점(Cafe's au lait macules), 모반, 베커 모반(Becker's Nevus), 반문상 모반(Nevus Spilus), 흑자(Lentigines), 흑색점, 진피 멜라닌세포성 병변(Dermal melanocytic lesions), 몽고반(Mongolian spot), 오타 모반(Nevus of Ota), 후천성 양측성 오타 모반양 반(Acquired bilateral nevus of Ota-like macules), 이토 모반(Nevus of Ito), 청색 모반(Blue nevus), 멜라닌형성세포성 모반(Melanocytic nevus), 경계 모반(Junctional nevus), 복합 모반(Compound nevus), 진피내 모반(Intradermal nevus), 운륜 모반(Halo nevus), 선천성 멜라닌세포성 모반(Congenital nevocytic nevus), 스피츠 모반(Spitz nevus), 이형성 모반(Dysplastic nevus), 임신성 갈색반(gravidic chloasma), 흑색종(Melanoma), 악성 흑자 흑색종(Lentigo maligna melanoma), 표재 확장성 흑색종(Superficial spreading melanoma), 선단 흑자성 흑색종(Acral lentiginous melanoma), 결절성 흑색종(Nodular melanoma), 색소성 기저세포암(pigment basal cell carcinoma), 색소성 피부섬유종(dermatofibromas), 색소성 피부낭종(dermoid cyst), 색소성 켈로이드(keloid), 일광 흑색증(solar lentigines), 색소성 편평태선(Lichen planus), 색소성 접촉피부염(Contact dermatitis), 자외선에 의한 색소 침착, 약물에 의한 색소 침착, 상처로 인한 색소 침착, 염증 후 색소 침착, 색소성 각질가시세포종(keratoacanthomas) 및 릴 흑피증(Riehl's melanosis) 등이 있으나, 이에 한정되는 것은 아니다. In the present invention, the pigment disease is a disease caused by pigmentation, and preferably, spots, freckles, age spots, blemishes, senile pigment spots, epidermal melanocytic lesions, milk coffee spots (Cafe's au lait macules) , nevus, Becker's nevus, nevus spilus, lentigines, lentigo, dermal melanocytic lesions, mongolian spot, nevus of Ota , Acquired bilateral nevus of Ota-like macules, Nevus of Ito, Blue nevus, Melanocytic nevus, Junctional nevus , compound nevus, intradermal nevus, halo nevus, congenital melanocytic nevus, Spitz nevus, dysplastic nevus, gestational brown Gravidic chloasma, Melanoma, Lentigo maligna melanoma, Superficial spreading melanoma, Acral lentiginous melanoma, Nodular melanoma ), pigment basal cell carcinoma, dermatofibromas, dermoid cyst, pigment keloid, solar lentigines, lichen planus pigment (Lichen planus), pigmented contact dermatitis ), pigmentation by ultraviolet rays, pigmentation by drugs, pigmentation by wounds, pigmentation after inflammation, pigmented keratoacanthomas, and Riehl's melanosis, but are not limited thereto. .
본 발명에서 "예방"은 본 발명의 식품 조성물을 이용하여 색소 침착에 기인한 색소 질환의 증상을 차단하거나, 그 증상의 억제 또는 지연시키는 모든 행위라면 제한없이 포함할 수 있다. In the present invention, "prevention" may include without limitation any act of blocking or suppressing or delaying the symptoms of pigmentation diseases caused by pigmentation by using the food composition of the present invention.
또한, 본 발명에서, "개선"은 본 발명의 식품 조성물을 이용하여 색소 침착에 기인한 색소 질환의 증상이 호전 또는 이롭게 변경되는 모든 행위라면 제한없이 포함할 수 있다. In addition, in the present invention, "improvement" may include without limitation any action in which symptoms of pigmentation diseases caused by pigmentation are improved or advantageously changed by using the food composition of the present invention.
본 발명의 식품 조성물은 각종 식품류, 예를 들어, 음료, 껌, 차, 비타민 복합제, 분말, 과립, 정제, 캡슐, 과자, 떡, 빵 등의 형태로 제조될 수 있다. 본 발명의 식품 조성물은 독성 및 부작용이 거의 없는 식물추출물로 구성된 것이므로 예방 목적으로 장기간 복용 시에도 안심하고 사용할 수 있다.The food composition of the present invention may be prepared in the form of various foods, for example, beverages, gum, tea, vitamin complexes, powders, granules, tablets, capsules, confectionery, rice cakes, and bread. Since the food composition of the present invention is composed of plant extracts with little toxicity and side effects, it can be safely used even when taken for a long period of time for preventive purposes.
본 발명의 조성물이 식품 조성물에 포함될 때 그 양은 전체 중량의 0.1 내지 50%의 비율로 첨가할 수 있다.When the composition of the present invention is included in a food composition, the amount may be added at a rate of 0.1 to 50% of the total weight.
여기서, 상기 식품 조성물이 음료 형태로 제조되는 경우 지시된 비율로 상기 식품 조성물을 함유하는 것 외에 특별한 제한점은 없으며 통상의 음료와 같이 여러가지 향미제 또는 천연 탄수화물 등을 추가 성분으로서 함유할 수 있다. 즉, 천연 탄수화물로서 포도당 등의 모노사카라이드, 과당 등의 디사카라이드, 슈크로스 등의 및 폴리사카라이드, 덱스트린, 시클로덱스트린 등과 같은 통상적인 당 및 자일리톨, 소르비톨, 에리트리톨 등의 당알콜 등을 포함할 수 있다. 상기 향미제로서는 천연 향미제(타우마틴, 스테비아 추출물(예를 들어 레바우디오시드 A, 글리시르히진등) 및 합성 향미제(사카린, 아스파르탐 등) 등을 들 수 있다. Here, when the food composition is prepared in the form of a beverage, there is no particular limitation except that the food composition is included in the indicated ratio, and various flavoring agents or natural carbohydrates may be included as additional ingredients as in conventional beverages. In other words, natural carbohydrates include monosaccharides such as glucose, disaccharides such as fructose, polysaccharides such as sucrose, and common sugars such as dextrin and cyclodextrin, and sugar alcohols such as xylitol, sorbitol, and erythritol. can do. Examples of the flavoring agent include natural flavoring agents (thaumatin, stevia extract (eg, rebaudioside A, glycyrrhizin, etc.) and synthetic flavoring agents (saccharin, aspartame, etc.).
그 외 본 발명의 식품 조성물은 여러 가지 영양제, 비타민, 광물(전해질), 합성 풍미제 및 천연 풍미제 등의 풍미제, 착색제, 펙트산 및 그의 염, 알긴산 및 그의 염, 유기산, 보호성 콜로이드 증점제, pH 조절제, 안정화제, 방부제, 글리세린, 알콜, 탄산 음료에 사용되는 탄산화제 등을 함유할 수 있다.In addition, the food composition of the present invention is various nutrients, vitamins, minerals (electrolytes), flavors such as synthetic flavors and natural flavors, colorants, pectic acid and its salts, alginic acid and its salts, organic acids, protective colloidal thickeners , pH adjusters, stabilizers, preservatives, glycerin, alcohol, carbonating agents used in carbonated beverages, and the like.
이러한 성분은 독립적으로 또는 조합하여 사용할 수 있다. 이러한 첨가제의 비율은 그렇게 중요하진 않지만 본 발명의 조성물 100 중량부 당 0.1 내지 약 50 중량부의 범위에서 선택되는 것이 일반적이다.These components may be used independently or in combination. The proportion of these additives is not critical, but is generally selected from the range of 0.1 to about 50 parts by weight per 100 parts by weight of the composition of the present invention.
본 발명의 또 다른 구현 예에 따르면, 하기 화학식 1로 표시되는 7-데스아세톡시-6,7-디하이드로게두닌 (7-Desacetoxy-6,7-dehydrogedunin; 7DG) 또는 이의 화장품학적으로 허용 가능한 염을 유효 성분으로 포함하는, 색소 질환의 예방 또는 개선용 화장료 조성물에 관한 것이다:According to another embodiment of the present invention, 7-desacetoxy-6,7-dehydrogedunin represented by Formula 1 below (7-Desacetoxy-6,7-dehydrogedunin; 7DG) or its cosmetically acceptable It relates to a cosmetic composition for preventing or improving pigment diseases, comprising a salt as an active ingredient:
[화학식 1][Formula 1]
본 발명에서 상기"화장품학적으로 허용 가능한 염"은, 양이온과 음이온이 정전기적 인력에 의해 결합하고 있는 물질인 염 중에서도 화장품학적으로 사용될 수 있는 형태의 염을 의미하며, 그 종류에 대한 구체적인 예는 상술한 "약제학적으로 허용되는 염"의 예를 포함할 수 있다.In the present invention, the "cosmetically acceptable salt" means a salt in a form that can be used cosmetically among salts in which cations and anions are bonded by electrostatic attraction, and specific examples of the type are Examples of the aforementioned "pharmaceutically acceptable salts" may be included.
본 발명의 화장료 조성물에 포함되는 성분은 유효 성분으로서의 상기 화학식 1 화합물 또는 이의 화장품학적으로 허용가능한 염 이외에 화장품 조성물에 통상적으로 이용되는 성분들을 포함할 수 있으며, 예컨대 항산화제, 안정화제, 용해화제, 비타민, 안료 및 향료와 같은 통상적인 보조제, 그리고 담체를 포함할 수 있으나, 이에 제한되는 것은 아니다. Ingredients included in the cosmetic composition of the present invention may include ingredients commonly used in cosmetic compositions in addition to the compound of Formula 1 or a cosmetically acceptable salt thereof as an active ingredient, such as antioxidants, stabilizers, solubilizers, Conventional adjuvants such as vitamins, pigments and flavors, and carriers may be included, but are not limited thereto.
본 발명의 화장료 조성물에서 7-데스아세톡시-6,7-디하이드로게두닌 (7-Desacetoxy-6,7-dehydrogedunin; 7DG) 화합물, 색소 질환 등에 관한 기재는 상기 색소 질환의 예방 또는 치료용 조성물에서 기재한 바와 동일하여, 본 명세서의 과도한 복잡성을 피하기 위하여 생략한다.In the cosmetic composition of the present invention, the description of the 7-Desacetoxy-6,7-dehydrogedunin (7DG) compound, pigment diseases, etc. is a composition for preventing or treating pigment diseases. It is the same as described in, and is omitted to avoid excessive complexity of the present specification.
본 발명의 화장료 조성물은 멜라닌 합성을 억제하거나 멜라닌 합성량을 감소시켜 색소 침착에 기인한 색소 질환을 효과적으로 예방 또는 개선할 수 있다.The cosmetic composition of the present invention can effectively prevent or improve pigment diseases caused by pigmentation by inhibiting melanin synthesis or reducing the amount of melanin synthesis.
본 발명에서 상기 색소 질환은 색소 침착에 기인한 질환으로, 바람직하게는 기미, 주근깨, 검버섯, 잡티, 노인성 색소반, 표피 멜라닌세포성 병변(Epidermal melanocytic lesion), 밀크커피 반점(Cafe's au lait macules), 모반, 베커 모반(Becker's Nevus), 반문상 모반(Nevus Spilus), 흑자(Lentigines), 흑색점, 진피 멜라닌세포성 병변(Dermal melanocytic lesions), 몽고반(Mongolian spot), 오타 모반(Nevus of Ota), 후천성 양측성 오타 모반양 반(Acquired bilateral nevus of Ota-like macules), 이토 모반(Nevus of Ito), 청색 모반(Blue nevus), 멜라닌형성세포성 모반(Melanocytic nevus), 경계 모반(Junctional nevus), 복합 모반(Compound nevus), 진피내 모반(Intradermal nevus), 운륜 모반(Halo nevus), 선천성 멜라닌세포성 모반(Congenital nevocytic nevus), 스피츠 모반(Spitz nevus), 이형성 모반(Dysplastic nevus), 임신성 갈색반(gravidic chloasma), 흑색종(Melanoma), 악성 흑자 흑색종(Lentigo maligna melanoma), 표재 확장성 흑색종(Superficial spreading melanoma), 선단 흑자성 흑색종(Acral lentiginous melanoma), 결절성 흑색종(Nodular melanoma), 색소성 기저세포암(pigment basal cell carcinoma), 색소성 피부섬유종(dermatofibromas), 색소성 피부낭종(dermoid cyst), 색소성 켈로이드(keloid), 일광 흑색증(solar lentigines), 색소성 편평태선(Lichen planus), 색소성 접촉피부염(Contact dermatitis), 자외선에 의한 색소 침착, 약물에 의한 색소 침착, 상처로 인한 색소 침착, 염증 후 색소 침착, 색소성 각질가시세포종(keratoacanthomas) 및 릴 흑피증(Riehl's melanosis) 등이 있으나, 이에 한정되는 것은 아니다.In the present invention, the pigment disease is a disease caused by pigmentation, and preferably, spots, freckles, age spots, blemishes, senile pigment spots, epidermal melanocytic lesions, milk coffee spots (Cafe's au lait macules) , nevus, Becker's nevus, nevus spilus, lentigines, lentigo, dermal melanocytic lesions, mongolian spot, nevus of Ota , Acquired bilateral nevus of Ota-like macules, Nevus of Ito, Blue nevus, Melanocytic nevus, Junctional nevus , compound nevus, intradermal nevus, halo nevus, congenital melanocytic nevus, Spitz nevus, dysplastic nevus, gestational brown Gravidic chloasma, Melanoma, Lentigo maligna melanoma, Superficial spreading melanoma, Acral lentiginous melanoma, Nodular melanoma ), pigment basal cell carcinoma, dermatofibromas, dermoid cyst, pigment keloid, solar lentigines, lichen planus pigment (Lichen planus), pigmented contact dermatitis ), pigmentation by ultraviolet rays, pigmentation by drugs, pigmentation by wounds, pigmentation after inflammation, pigmented keratoacanthomas, and Riehl's melanosis, but are not limited thereto. .
본 발명에서 "예방"은 본 발명의 화장료 조성물을 이용하여 색소 침착에 기인한 색소 질환의 증상을 차단하거나, 그 증상의 억제 또는 지연시키는 모든 행위라면 제한없이 포함할 수 있다. In the present invention, "prevention" may include without limitation any act of blocking or suppressing or delaying the symptoms of pigmentation diseases caused by pigmentation by using the cosmetic composition of the present invention.
또한, 본 발명에서 "개선"은 본 발명의 화장료 조성물을 이용하여 색소 침착에 기인한 색소 질환의 증상이 호전 또는 이롭게 변경되는 모든 행위라면 제한없이 포함할 수 있다. In addition, in the present invention, "improvement" may include without limitation any action in which the symptoms of pigmentation diseases caused by pigmentation are improved or advantageously changed by using the cosmetic composition of the present invention.
본 발명에서 화장료 조성물은 화장수, 영양로션, 영양에센스, 마사지 크림, 미용목욕물첨가제, 바디로션, 바디밀크, 배스오일, 베이비오일, 베이비파우더, 샤워겔, 샤워크림, 선스크린로션, 선스크린크림, 선탠크림, 스킨로션, 스킨크림, 자외선차단용 화장품, 크렌징밀크, 탈모제{화장용}, 페이스 및 바디로션, 페이스 및 바디크림, 피부미백크림, 핸드로션, 헤어로션, 화장용크림, 쟈스민오일, 목욕비누, 물비누, 미용비누, 샴푸, 손세정제(핸드클리너), 약용비누{비의료용}, 크림비누, 페이셜 워시, 전신 세정제, 두피 세정제, 헤어린스, 화장비누, 치아미백용 겔, 치약 등의 형태로 제조될 수 있다. 이를 위해 본 발명의 조성물은 화장료 조성물의 제조에 통상적으로 사용하는 용매나, 적절한 담체, 부형제 또는 희석제를 더 포함할 수 있다.In the present invention, the cosmetic composition is lotion, nutrient lotion, nutrient essence, massage cream, beauty bath water additive, body lotion, body milk, bath oil, baby oil, baby powder, shower gel, shower cream, sunscreen lotion, sunscreen cream, Suntan cream, skin lotion, skin cream, sunscreen cosmetics, cleansing milk, depilatory agent {cosmetic}, face and body lotion, face and body cream, skin whitening cream, hand lotion, hair lotion, cosmetic cream, jasmine oil, Bath soap, water soap, beauty soap, shampoo, hand sanitizer (hand cleaner), medicated soap (non-medical use), cream soap, facial wash, body cleanser, scalp cleanser, hair rinse, cosmetic soap, tooth whitening gel, toothpaste, etc. can be made in the form To this end, the composition of the present invention may further include a solvent or an appropriate carrier, excipient or diluent commonly used in the preparation of cosmetic compositions.
본 발명의 화장료 조성물 내에 더 추가될 수 있는 용매의 종류는 특별히 한정하지 않으나, 예를 들어, 물, 식염수, DMSO 또는 이들의 조합을 사용할 수 있고, 담체, 부형제 또는 희석제로는 정제수, 오일, 왁스, 지방산, 지방산 알콜, 지방산 에스테르, 계면활성제, 흡습제(humectant), 증점제, 항산화제, 점도 안정화제, 킬레이팅제, 완충제, 저급 알콜 등이 포함되지만, 이에 제한되는 것은 아니다. 또한, 필요에 따라 미백제, 보습제, 비타민, 자외선 차단제, 향수, 염료, 항생제, 항박테리아제, 항진균제를 포함할 수 있다. The type of solvent that can be further added to the cosmetic composition of the present invention is not particularly limited, but for example, water, saline, DMSO, or a combination thereof may be used, and purified water, oil, or wax may be used as a carrier, excipient, or diluent. , fatty acids, fatty alcohols, fatty acid esters, surfactants, humectants, thickeners, antioxidants, viscosity stabilizers, chelating agents, buffers, lower alcohols, and the like, but are not limited thereto. In addition, whitening agents, moisturizing agents, vitamins, sunscreens, perfumes, dyes, antibiotics, antibacterial agents, and antifungal agents may be included as necessary.
상기 오일로서는 수소화 식물성유, 피마자유, 면실유, 올리브유, 야자인유, 호호바유, 아보카도유가 이용될 수 있으며, 왁스로는 밀랍, 경랍, 카르나우바, 칸델릴라, 몬탄, 세레신, 액체 파라핀, 라놀린이 이용될 수 있다.Hydrogenated vegetable oil, castor oil, cottonseed oil, olive oil, coconut oil, jojoba oil, and avocado oil may be used as the oil, and beeswax, spermaceti, carnauba, candelilla, montan, ceresin, liquid paraffin, and lanolin may be used as the wax. can be used
지방산으로는 스테아르산, 리놀레산, 리놀렌산, 올레산이 이용될 수 있고, 지방산 알콜로는 세틸 알콜, 옥틸 도데칸올, 올레일 알콜, 판텐올, 라놀린 알콜, 스테아릴 알콜, 헥사데칸올이 이용될 수 있으며 지방산 에스테르로는 이소프로필 미리스테이트, 이소프로필 팔미테이트, 부틸 스테아레이트가 이용될 수 있다. 계면 활성제로는 당업계에 알려진 양이온 계면활성제, 음이온 계면활성제 및 비이온성 계면활성제가 사용가능하며 가능한 한 천연물 유래의 계면활성제가 바람직하다.As fatty acids, stearic acid, linoleic acid, linolenic acid, and oleic acid may be used, and as fatty alcohols, cetyl alcohol, octyl dodecanol, oleyl alcohol, panthenol, lanolin alcohol, stearyl alcohol, and hexadecanol may be used. As the fatty acid ester, isopropyl myristate, isopropyl palmitate, and butyl stearate may be used. As surfactants, cationic surfactants, anionic surfactants, and nonionic surfactants known in the art can be used, and surfactants derived from natural products are preferred as much as possible.
그 외에도 화장품 분야에서 널리 알려진 흡습제, 증점제, 항산화제 등을 포함할 수 있으며, 이들의 종류와 양은 당업계에 공지된 바에 따른다.In addition, it may include a moisture absorbent, thickener, antioxidant, etc. widely known in the field of cosmetics, and the type and amount thereof are known in the art.
본 발명의 또 다른 구현 예에 따르면, 하기 화학식 1로 표시되는 7-데스아세톡시-6,7-디하이드로게두닌 (7-Desacetoxy-6,7-dehydrogedunin; 7DG) 또는 이의 약제학 또는 화장품학적으로 허용 가능한 염을 유효 성분으로 포함하는, 미백용 조성물에 관한 것이다:According to another embodiment of the present invention, 7-desacetoxy-6,7-dihydrogedunin represented by Formula 1 below (7-Desacetoxy-6,7-dehydrogedunin; 7DG) or its pharmaceutical or cosmetic It relates to a composition for whitening comprising an acceptable salt as an active ingredient:
[화학식 1][Formula 1]
본 발명의 미백용 조성물에서 7-데스아세톡시-6,7-디하이드로게두닌 (7-Desacetoxy-6,7-dehydrogedunin; 7DG) 화합물, 약제학적으로 허용가능한 염, 화장품학적으로 허용 가능한 염 등에 관한 기재는 상기 색소 질환의 예방 또는 치료용 조성물에서 기재한 바와 동일하여, 본 명세서의 과도한 복잡성을 피하기 위하여 생략한다.In the whitening composition of the present invention, a 7-desacetoxy-6,7-dehydrogedunin (7-Desacetoxy-6,7-dehydrogedunin; 7DG) compound, a pharmaceutically acceptable salt, a cosmetically acceptable salt, etc. The related description is the same as that described in the composition for preventing or treating pigmented diseases, and is omitted to avoid excessive complexity in the present specification.
본 발명의 미백용 조성물은 멜라닌 합성을 억제하거나 멜라닌 합성량을 감소시켜 피부 톤을 맑게 하거나, 색소 침착을 개선하는 미백 효능이 매우 뛰어나다. The composition for whitening of the present invention has excellent whitening efficacy of suppressing melanin synthesis or reducing the amount of melanin synthesis to brighten skin tone or improve pigmentation.
본 발명에서 상기 미백은 멜라닌 색소의 합성을 저해함으로써 피부 톤이 밝아 지게 할 뿐만 아니라, 환경, 호르몬 또는 유전에 기인한 피부 색소 침착을 개선하는 것을 의미하는 것이나, 이에 한정되는 것은 아니다.In the present invention, the whitening means not only to brighten the skin tone by inhibiting the synthesis of melanin pigment, but also to improve skin pigmentation due to environment, hormones or genetics, but is not limited thereto.
본 발명에서 상기 미백용 조성물은 화장료 조성물 또는 의약외품 조성물로 활용될 수 있으며, 상기 조성물은 용액, 외용 연고, 크림, 폼, 영양 화장수, 유연 화장수, 팩, 유연수, 유액, 메이크업 베이스, 에센스, 비누, 액체 세정료, 입욕제, 선 스크린 크림, 선 오일, 현탁액, 유탁액, 페이스트, 겔, 로션, 파우더, 비누, 계면 활성제-함유 클렌징, 오일, 분말 파운데이션, 유탁액 파운데이션, 왁스 파운데이션, 패취 및 스프레이로 이루어진 군으로부터 선택되는 적어도 하나의 제형을 가지는 것일 수 있으나, 이에 한정되는 것은 아니다.In the present invention, the whitening composition may be used as a cosmetic composition or a quasi-drug composition, and the composition may be used as a solution, external ointment, cream, foam, nutrient lotion, softening lotion, pack, softening water, emulsion, makeup base, essence, soap, As liquid cleansers, bath powders, sunscreen creams, sun oils, suspensions, emulsions, pastes, gels, lotions, powders, soaps, surfactant-containing cleansers, oils, powder foundations, emulsion foundations, wax foundations, patches and sprays It may have at least one formulation selected from the group consisting of, but is not limited thereto.
본 발명의 미백용 조성물 내에 더 추가될 수 있는 용매의 종류는 특별히 한정하지 않으나, 예를 들어, 물, 식염수, DMSO 또는 이들의 조합을 사용할 수 있고, 담체, 부형제 또는 희석제로는 정제수, 오일, 왁스, 지방산, 지방산 알콜, 지방산 에스테르, 계면활성제, 흡습제(humectant), 증점제, 항산화제, 점도 안정화제, 킬레이팅제, 완충제, 저급 알콜 등이 포함되지만, 이에 제한되는 것은 아니다. 또한, 필요에 따라 미백제, 보습제, 비타민, 자외선 차단제, 향수, 염료, 항생제, 항박테리아제, 항진균제를 포함할 수 있다. The type of solvent that can be further added to the whitening composition of the present invention is not particularly limited, but for example, water, saline, DMSO, or a combination thereof may be used, and carriers, excipients, or diluents include purified water, oil, waxes, fatty acids, fatty alcohols, fatty acid esters, surfactants, humectants, thickeners, antioxidants, viscosity stabilizers, chelating agents, buffers, lower alcohols, and the like, but are not limited thereto. In addition, whitening agents, moisturizing agents, vitamins, sunscreens, perfumes, dyes, antibiotics, antibacterial agents, and antifungal agents may be included as necessary.
상기 오일로서는 수소화 식물성유, 피마자유, 면실유, 올리브유, 야자인유, 호호바유, 아보카도유가 이용될 수 있으며, 왁스로는 밀랍, 경랍, 카르나우바, 칸델릴라, 몬탄, 세레신, 액체 파라핀, 라놀린이 이용될 수 있다.Hydrogenated vegetable oil, castor oil, cottonseed oil, olive oil, coconut oil, jojoba oil, and avocado oil may be used as the oil, and beeswax, spermaceti, carnauba, candelilla, montan, ceresin, liquid paraffin, and lanolin may be used as the wax. can be used
지방산으로는 스테아르산, 리놀레산, 리놀렌산, 올레산이 이용될 수 있고, 지방산 알콜로는 세틸 알콜, 옥틸 도데칸올, 올레일 알콜, 판텐올, 라놀린 알콜, 스테아릴 알콜, 헥사데칸올이 이용될 수 있으며 지방산 에스테르로는 이소프로필 미리스테이트, 이소프로필 팔미테이트, 부틸 스테아레이트가 이용될 수 있다. 계면 활성제로는 당업계에 알려진 양이온 계면활성제, 음이온 계면활성제 및 비이온성 계면활성제가 사용가능하며 가능한 한 천연물 유래의 계면활성제가 바람직하다.As fatty acids, stearic acid, linoleic acid, linolenic acid, and oleic acid may be used, and as fatty alcohols, cetyl alcohol, octyl dodecanol, oleyl alcohol, panthenol, lanolin alcohol, stearyl alcohol, and hexadecanol may be used. As the fatty acid ester, isopropyl myristate, isopropyl palmitate, and butyl stearate may be used. As surfactants, cationic surfactants, anionic surfactants, and nonionic surfactants known in the art can be used, and surfactants derived from natural products are preferred as much as possible.
그 외에도 화장품 또는 의약외품 분야에서 널리 알려진 흡습제, 증점제, 항산화제 등을 포함할 수 있으며, 이들의 종류와 양은 당업계에 공지된 바에 따른다.In addition, it may include moisture absorbents, thickeners, antioxidants, etc., which are widely known in the field of cosmetics or quasi-drugs, and the types and amounts thereof are known in the art.
본 발명의 또 다른 구현 예에 따르면, 투여가 필요한 대상체에게 하기 화학식 1로 표시되는 7-데스아세톡시-6,7-디하이드로게두닌 (7-Desacetoxy-6,7-dehydrogedunin; 7DG) 또는 이의 약제학 또는 화장품학적으로 허용 가능한 염을 유효 성분으로 포함하는 조성물을 유효한 양으로 투여하는 단계를 포함하는, 색소 질환의 예방, 개선 또는 치료 방법에 관한 것이다:According to another embodiment of the present invention, 7-desacetoxy-6,7-dehydrogedunin represented by Formula 1 below (7-Desacetoxy-6,7-dehydrogedunin; 7DG) or its It relates to a method for preventing, improving or treating pigment diseases, comprising administering an effective amount of a composition comprising a pharmaceutically or cosmetically acceptable salt as an active ingredient:
[화학식 1][Formula 1]
본 발명의 상기 색소 질환의 예방, 개선 또는 치료 방법에서, 7-데스아세톡시-6,7-디하이드로게두닌 (7-Desacetoxy-6,7-dehydrogedunin; 7DG) 화합물, 약제학적으로 허용가능한 염, 화장품학적으로 허용가능한 염, 색소 질환 등에 관한 기재는 상기 색소 질환의 예방 또는 치료용 조성물에서 기재한 바와 동일하여, 본 명세서의 과도한 복잡성을 피하기 위하여 생략한다.In the method for preventing, improving or treating pigmented diseases of the present invention, a 7-desacetoxy-6,7-dihydrogedunin (7-Desacetoxy-6,7-dehydrogedunin; 7DG) compound, a pharmaceutically acceptable salt , cosmetically acceptable salts, pigment diseases, etc. are the same as those described in the composition for preventing or treating pigment diseases, and thus are omitted to avoid excessive complexity in the present specification.
본 발명에서 상기 "투여"는 임의의 적절한 방법으로 대상체에 소정의 본 발명의 화합물을 제공하는 것을 의미한다. In the present invention, the "administration" means providing a given compound of the present invention to a subject by any suitable method.
본 발명에서 상기 투여가 필요한 "대상체"는 포유동물 및 비-포유동물을 모두 포함할 수 있다. 여기서, 상기 포유동물의 예로는 인간, 비-인간 영장류, 예컨대 침팬지, 다른 유인원 또는 원숭이 종; 축산 동물, 예컨대 소, 말, 양, 염소, 돼지; 사육 동물, 예컨대 토끼, 개 또는 고양이; 실험 동물, 예를 들어 설치류, 예컨대 래트, 마우스 또는 기니아 피그 등을 포함할 수 있으나, 이에 제한되는 것은 아니다. 또한, 본 발명에서 상기 비-포유동물의 예로는 조류 또는 어류 등을 포함할 수 있으나, 이에 제한되는 것은 아니다. In the present invention, the "subject" in need of the administration may include both mammals and non-mammals. Here, examples of the mammal include humans, non-human primates such as chimpanzees, other apes or monkey species; livestock animals such as cattle, horses, sheep, goats, pigs; domesticated animals such as rabbits, dogs or cats; Laboratory animals, such as rodents, such as rats, mice, or guinea pigs may be included, but are not limited thereto. In addition, examples of the non-mammals in the present invention may include birds or fish, but are not limited thereto.
본 발명에서 상기와 같이 투여되는 화합물의 제제는 특별히 제한하지 않으며, 고체 형태의 제제, 액체 형태의 제제, 반고체 형태의 제제 또는 에어로졸 제제로 투여될 수 있으며, 사용하기 바로 전에 경구 또는 비경구 투여용 액체 형태 제제로 전환되도록 의도되는 고체 형태 제제로 투여될 수 있고, 예를 들면, 산제, 과립제, 캡슐, 정제, 수성 현탁액 등의 경구형 제형, 외용제, 좌제 및 멸균 주사용액의 형태로 제형화하여 투여될 수 있고, 비경구 투여용 제제는 주사제, 점적제, 연고, 로션, 스프레이, 현탁제, 유제, 좌제 등의 형태로 투여될 수 있으나, 이에 제한되는 것은 아니다. In the present invention, the formulation of the compound administered as described above is not particularly limited, and may be administered as a solid formulation, liquid formulation, semi-solid formulation or aerosol formulation, for oral or parenteral administration immediately before use. It can be administered as a solid form preparation intended to be converted into a liquid form preparation, and is formulated in the form of, for example, oral preparations such as powders, granules, capsules, tablets, aqueous suspensions, external preparations, suppositories and sterile injection solutions. It may be administered, and preparations for parenteral administration may be administered in the form of injections, drops, ointments, lotions, sprays, suspensions, emulsions, suppositories, etc., but are not limited thereto.
또한, 본 발명에서 상기 투여 시 본 발명의 화합물과 함께 약학적으로 허용 가능한 담체를 추가로 투여할 수 있다. 여기서, 상기 약학적으로 허용되는 담체는 경구 또는 비경구 투여 시에는 결합제, 활탁제, 붕해제, 부형제, 가용화제, 분산제, 안정화제, 현탁화제, 색소, 향료 등을 사용할 수 있으며, 주사제의 경우에는 완충제, 보존제, 무통화제, 가용화제, 등장제, 안정화제 등을 혼합하여 사용할 수 있으며, 국소투여용의 경우에는 기제, 부형제, 윤활제, 보존제 등을 사용할 수 있다. 본 발명의 화합물의 제형은 상술한 바와 같은 약학적으로 허용되는 담체와 혼합하여 다양하게 제조될 수 있다. In addition, in the present invention, a pharmaceutically acceptable carrier may be additionally administered together with the compound of the present invention during the administration. Here, the pharmaceutically acceptable carrier may be a binder, a lubricant, a disintegrant, an excipient, a solubilizer, a dispersant, a stabilizer, a suspending agent, a coloring agent, a flavoring agent, etc. for oral or parenteral administration. A buffer, preservative, analgesic agent, solubilizer, isotonic agent, stabilizer, etc. may be mixed and used, and in the case of topical administration, a base, excipient, lubricant, preservative, etc. may be used. Formulations of the compound of the present invention can be variously prepared by mixing with the pharmaceutically acceptable carriers described above.
한편, 제제화에 적합한 담체, 부형제 및 희석제의 예로는, 락토즈, 덱스트로즈, 수크로즈, 솔비톨, 만니톨, 자일리톨, 에리스리톨, 말티톨, 전분, 아카시아 고무, 알지네이트, 젤라틴, 칼슘 포스페이트, 칼슘 실리케이트, 셀룰로즈, 메틸 셀룰로즈, 미정질 셀룰로즈, 폴리비닐피롤리돈, 물, 메틸하이드록시벤조에이트, 프로필하이드록시벤조에이트, 탈크, 마그네슘 스테아레이트 또는 광물유 등이 사용될 수 있다. 또한, 충진제, 항응집제, 윤활제, 습윤제, 향료, 유화제, 방부제 등을 추가로 포함할 수 있다.On the other hand, examples of carriers, excipients and diluents suitable for formulation include lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, acacia gum, alginate, gelatin, calcium phosphate, calcium silicate, cellulose , methyl cellulose, microcrystalline cellulose, polyvinylpyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate or mineral oil, and the like can be used. In addition, fillers, anti-coagulants, lubricants, wetting agents, flavoring agents, emulsifiers, preservatives, and the like may be further included.
본 발명에 따른 화합물의 투여 경로는 이들로 한정되는 것은 아니지만 경구 또는 비경구 투하가 바람직하다. The route of administration of the compound according to the present invention is not limited thereto, but oral or parenteral administration is preferred.
본 발명에서, "비경구"는 피하, 피내, 정맥내, 근육내, 관절내, 활액낭내, 흉골내, 경막내, 병소내 및 두개골내 주사 또는 주입기술을 포함한다. In the present invention, "parenteral" includes subcutaneous, intradermal, intravenous, intramuscular, intraarticular, intracapsular, intrasternal, intrathecal, intralesional and intracranial injection or infusion techniques.
본 발명에서, "유효한 양"은 바람직한 생물학적 결과를 제공하기 위한 작용제의 충분한 양을 지칭한다. 상기 결과는 질환의 징후, 증상 또는 원인의 감소 및/또는 완화, 또는 생물계의 임의의 다른 바람직한 변화일 수 있다. 예를 들어, 치료 용도를 위한 "유효량"은 질환에서 임상적으로 유의한 감소를 제공하는데 요구되는, 본 발명에 개시된 화합물의 양이다. 임의의 개별적인 경우에서 적절한 "효과적인" 양은 일상적인 실험을 사용하여 당업자에 의해 결정될 수 있다. 따라서, 표현 "유효량"은 일반적으로 활성 물질이 치료 효과를 갖는 양을 지칭한다. 본 발명의 경우에, 활성 물질은 화학식 1로 표시되는 7-데스아세톡시-6,7-디하이드로게두닌 화합물이자, 색소 질환의 예방, 개선 또는 치료제이다.In the present invention, "an effective amount" refers to an amount of an agent sufficient to provide a desired biological result. The result may be reduction and/or alleviation of the signs, symptoms or causes of a disease, or any other desirable change in a biological system. For example, an “effective amount” for therapeutic use is the amount of a compound disclosed herein required to provide a clinically significant reduction in disease. An "effective" amount suitable in any individual case can be determined by one skilled in the art using routine experimentation. Thus, the expression “effective amount” generally refers to an amount of an active substance that has a therapeutic effect. In the case of the present invention, the active substance is a 7-desacetoxy-6,7-dihydrogedunin compound represented by formula (1), and is a preventive, ameliorative, or therapeutic agent for pigment diseases.
본 발명의 화합물은 사용된 특정 화합물의 활성, 연령, 체중, 일반적인 건강, 성별, 정식, 투여 시간, 투여 경로, 배출율, 약물 배합 및 예방 또는 치료될 특정 질환의 여러 요인에 따라 다양하게 변할 수 있고, 상기 화합물의 투여량은 환자의 상태, 체중, 질병의 정도, 약물 형태, 투여 경로 및 기간에 따라 다르지만 당업자에 의해 적절하게 선택될 수 있고, 1일 0.0001 내지 100mg/kg 또는 0.001 내지 100mg/kg으로 투여할 수 있다. 투여는 하루에 한번 투여할 수도 있고, 수회 나누어 투여할 수도 있다. 상기 투여량은 어떠한 면으로든 본 발명의 범위를 한정하는 것은 아니다. 본 발명에 따른 화합물은 환제, 당의정, 캡슐, 액제, 겔, 시럽, 슬러리, 현탁제로 제형화될 수 있다.The compound of the present invention can vary widely depending on the activity of the specific compound used, age, body weight, general health, sex, diet, administration time, route of administration, excretion rate, drug combination and various factors of the specific disease to be prevented or treated, , The dosage of the compound varies depending on the patient's condition, weight, disease severity, drug form, administration route and period, but can be appropriately selected by those skilled in the art, and is 0.0001 to 100 mg/kg or 0.001 to 100 mg/kg per day. can be administered with Administration may be administered once a day, or may be administered in several divided doses. The dosage is not intended to limit the scope of the present invention in any way. The compounds according to the present invention may be formulated as pills, dragees, capsules, solutions, gels, syrups, slurries and suspensions.
본 발명의 화합물은 단독으로, 또는 호르몬 치료, 화학 치료 및 생물학적 반응 조절제를 사용하는 방법들과 병용하여 사용할 수 있다.The compounds of the present invention can be used alone or in combination with methods using hormone therapy, chemotherapy and biological response modifiers.
본 발명에서 제공하는 조성물은 인체에 독성을 일으키지 않으면서도 멜라닌 생성 및 합성을 효과적으로 억제하여 피부 미백 효과가 뛰어나며, 색소 침착에 기인한 기미, 주근깨, 노인성 색소반, 잡티, 모반 또는 일광흑색증(solar lentigines) 등의 색소 질환을 예방, 개선 또는 치료할 수 있다.The composition provided by the present invention has excellent skin whitening effect by effectively inhibiting melanin production and synthesis without causing toxicity to the human body, and has excellent skin whitening effect. lentigines) can be prevented, improved or treated.
도 1은 본 발명의 일 실시예에 따른 고속 탐색 기술(high-throughput screening)을 통해 선별된 천연 화합물 및 임상 화합물을 후보 물질로 하여 멜라닌 억제 효과를 확인하여 발굴하는 과정을 나타낸 도이다.1 is a diagram illustrating a process of identifying and discovering melanin inhibitory effects using natural compounds and clinical compounds selected through high-throughput screening as candidate substances according to an embodiment of the present invention.
도 2는 본 발명의 일 실시예에 따른 멜라닌 세포에 대하여 7-데스아세톡시-6,7-디하이드로게두닌(7-Desacetoxy-6,7-dehydrogedunin; 7DG) 화합물 처리 후 세포 생존율의 변화를 측정한 결과를 그래프로 나타낸 도이다. Figure 2 shows the change in cell viability after treatment with 7-Desacetoxy-6,7-dehydrogedunin (7DG) compound for melanocytes according to an embodiment of the present invention. It is a graph showing the measured results.
도 3a 및 도 3b는 본 발명의 일 실시예에 따른 멜라닌 세포에 7DG 화합물을 처리한 후 멜라닌 합성에 관여하는 gp100, MITF 및 타이로시나아제의 발현 수준의 변화를 웨스턴블랏을 통해 측정한 결과를 나타낸 도이다.Figures 3a and 3b show the results of measuring the changes in the expression levels of gp100, MITF and tyrosinase involved in melanin synthesis after treatment of melanocytes with a 7DG compound according to an embodiment of the present invention through Western blotting. is the diagram shown.
도 4a 및 도 4b는 본 발명의 일 실시예에 따른 멜라닌 세포에 7DG 화합물을 처리하고 72 시간 후 타이로시나아제 활성도를 평가하기 위해 지모그래피(zymography) 분석한 결과를 나타낸 도이다.4a and 4b are diagrams showing the results of zymography analysis to evaluate tyrosinase activity after 72 hours of treating melanocytes with a 7DG compound according to an embodiment of the present invention.
도 5a 및 도 5b는 본 발명의 일 실시예에 따른 멜라닌 세포에 7DG 화합물을 처리하고 4 일 후 멜라닌 수준의 변화를 측정한 결과를 나타낸 도이다.Figures 5a and 5b is a diagram showing the results of measuring the change in melanin level after 4 days of treating melanocytes with a 7DG compound according to an embodiment of the present invention.
도 6a 및 도 6b는 본 발명의 일 실시예에 따른 UVB에 노출된 사람 피부 조직에 7DG 화합물 처리에 따른 멜라닌 형성 억제 효과를 확인하기 위하여 멕사미터(Mexameter)를 이용하여 멜라닌 수치를 측정한 결과를 나타낸 도이다.6a and 6b show the results of measuring melanin levels using a Mexameter in order to confirm the melanin formation inhibitory effect of the 7DG compound treatment on human skin tissue exposed to UVB according to an embodiment of the present invention is the diagram shown.
도 7은 본 발명의 일 실시예에 따른 UVB에 노출된 사람 피부 조직에 7DG 화합물 처리에 따른 멜라닌 형성 억제 효과를 확인하기 위하여 폰타나-마손 염색법 (Fontana-Masson stainig)에 의한 멜라닌 세포의 분포를 현미경을 통해 확인한 결과를 나타낸 도이다.7 is a microscopic view of the distribution of melanocytes by Fontana-Masson staining in order to confirm the melanin formation inhibitory effect according to the 7DG compound treatment in human skin tissue exposed to UVB according to an embodiment of the present invention. It is a diagram showing the result confirmed through .
본 발명의 일 구현 예에서는 하기 화학식 1로 표시되는 화합물 또는 이의 약제학적으로 허용 가능한 염을 유효 성분으로 포함하는, 색소 질환의 예방 또는 치료용 약학 조성물에 관한 것이다.One embodiment of the present invention relates to a pharmaceutical composition for preventing or treating pigmentary diseases, comprising a compound represented by Formula 1 below or a pharmaceutically acceptable salt thereof as an active ingredient.
본 발명의 다른 구현 예에서는 하기 화학식 1로 표시되는 화합물 또는 이의 약제학적으로 허용 가능한 염을 유효 성분으로 포함하는, 색소 질환의 예방 또는 개선용 식품 조성물에 관한 것이다.Another embodiment of the present invention relates to a food composition for preventing or improving pigment diseases, comprising a compound represented by Formula 1 below or a pharmaceutically acceptable salt thereof as an active ingredient.
본 발명의 또 다른 구현 예에서는 하기 화학식 1로 표시되는 화합물 또는 이의 화장품학적으로 허용 가능한 염을 유효 성분으로 포함하는, 색소 질환의 예방 또는 개선용 화장료 조성물에 관한 것이다.Another embodiment of the present invention relates to a cosmetic composition for preventing or improving pigment diseases, comprising a compound represented by Formula 1 below or a cosmetically acceptable salt thereof as an active ingredient.
본 발명의 또 다른 구현 예에서는 하기 화학식 1로 표시되는 화합물 또는 이의 화장품학적으로 허용 가능한 염을 유효 성분으로 포함하는, 미백용 화장료 조성물에 관한 것이다.Another embodiment of the present invention relates to a cosmetic composition for whitening comprising a compound represented by Formula 1 below or a cosmetically acceptable salt thereof as an active ingredient.
본 발명의 또 다른 구현 예에서는 하기 화학식 1로 표시되는 화합물 또는 이의 화장품학적으로 허용 가능한 염을 유효 성분으로 포함하는, 미백용 의약외품 조성물에 관한 것이다.Another embodiment of the present invention relates to a quasi-drug composition for whitening comprising a compound represented by Formula 1 below or a cosmetically acceptable salt thereof as an active ingredient.
본 발명의 또 다른 구현 예에서는 투여가 필요한 대상체에게 하기 화학식 1로 표시되는 화합물 또는 이의 약제학 또는 화장품학적으로 허용 가능한 염을 유효한 양으로 투여하는 단계를 포함하는, 색소 질환의 예방, 개선 또는 치료 방법에 관한 것이다.In another embodiment of the present invention, a method for preventing, improving or treating pigmented diseases comprising administering an effective amount of a compound represented by Formula 1 or a pharmaceutically or cosmetically acceptable salt thereof to a subject in need of administration. It is about.
[화학식 1][Formula 1]
이하, 실시예를 통하여 본 발명을 더욱 상세히 설명하고자 한다. 이들 실시예는 오로지 본 발명을 보다 구체적으로 설명하기 위한 것으로, 본 발명의 요지에 따라 본 발명의 범위가 이들 실시예에 의해 제한되지 않는다는 것은 당업계에서 통상의 지식을 가진 자에 있어서 자명할 것이다.Hereinafter, the present invention will be described in more detail through examples. These examples are only for explaining the present invention in more detail, and it will be apparent to those skilled in the art that the scope of the present invention is not limited by these examples according to the gist of the present invention. .
실시예 1: 7-데스아세톡시-6,7-디하이드로게두닌(7-Desacetoxy-6,7-dehydrogedunin; 7DG) 화합물의 세포 독성 평가Example 1: Evaluation of cytotoxicity of 7-desacetoxy-6,7-dehydrogedunin (7-Desacetoxy-6,7-dehydrogedunin; 7DG) compound
형광 현미경 및 유세포분석기를 이용하여 대량의 라이브러리로부터 멜라닌 세포(primary melanocyte)에서 고속 탐색 기술(high-throughput screening)을 통해 특정 단백질과 상호 작용하는 후보 물질 군(천연 화합물 또는 임상 화합물)을 스크리닝하였고, 최종적으로 7-데스아세톡시-6,7-디하이드로게두닌(7-Desacetoxy-6,7-dehydrogedunin; 7DG) 화합물을 발굴하였다(도 1 참조). 상기에서 발굴된 7DG 화합물의 세포 독성에 영향을 주지 않는 적정 농도를 확인하고자 하였다. 인간 표피 멜라닌 세포(primary human epidermal melanocyte)를 96-웰 플레이트에 1.0 X 104 세포로 분주하고 배양한 뒤 7DG 화합물을 0.1 μM, 0.2 μM, 0.5 μM, 1 μM, 2 μM, 5 μM 또는 10 μM의 농도로 처리하였고, 그로부터 4 일 후에 MTT 시약을 이용하여 세포 생존율의 변화를 측정하여 그 결과를 도 2에 나타내었다. A group of candidate substances (natural compounds or clinical compounds) interacting with a specific protein was screened through high-throughput screening in primary melanocytes from a large library using fluorescence microscopy and flow cytometry, Finally, 7-Desacetoxy-6,7-dihydrogedunin (7-Desacetoxy-6,7-dehydrogedunin; 7DG) compound was discovered (see FIG. 1). An appropriate concentration that does not affect the cytotoxicity of the 7DG compound discovered above was confirmed. Human epidermal melanocytes (primary human epidermal melanocytes) were divided into 1.0 X 10 4 cells in a 96-well plate, cultured, and 7DG compound was added at 0.1 μM, 0.2 μM, 0.5 μM, 1 μM, 2 μM, 5 μM, or 10 μM. It was treated at a concentration of , and after 4 days from that, the change in cell viability was measured using the MTT reagent, and the results are shown in FIG. 2 .
실험 결과 도 2에서 보는 바와 같이, 7DG 화합물은 5 μM 이하의 농도 범위에서는 세포 독성이 없는 것을 확인할 수 있었다. Experimental results As shown in Figure 2, it was confirmed that the 7DG compound is not cytotoxic in the concentration range of 5 μM or less.
실시예 2: 7DG 화합물의 멜라닌 형성 억제 효과(1) - 타이로시나아제 활성 평가Example 2: Melanin formation inhibitory effect of 7DG compound (1) - evaluation of tyrosinase activity
6 웰 플레이트에 1 차 멜라닌 세포(primary melanocytes) 3 x 105 개 세포를 시딩하고, P2X7 수용체 안타고니스트(P2X7 receptor antagonist)인 7DG를 농도 별로 0.5 μM, 1 μM 또는 2 μM을 30 분간 처리하였다. 3 일 후, 세포 펠렛(pellet)에 용혈 버퍼를 첨가한 후 4 ℃에서 30 분간 반응하여 원심 분리(4 ℃, 10 분)하였다. 상층액(supernatant)만 새로운 e.p 튜브(tube)로 옮긴 후 BCA 어쎄이(assay)를 이용하여 단백질 정량을 수행하였다. 10 % 폴리아크릴아마이드 겔(polyacrylamide gel)에 전기영동하여 니트로셀룰로오스 막(nitrocellulose membrane)에 이동시켰다. 항-타이로시나아제와 막(membrane)을 4 ℃에서 밤새 반응시키고, ECL 키트를 이용하여 밴드(band)를 확인하였고, 멜라닌 합성에 관여하는 단백질인 멜라닌소체 내 당단백질(glycoprotein; gp100), 마이크로프탈미아 연관 전사인자(microphthalmia-associated transcriptian factor; MITF) 및 타이로시나아제(Tyrosinase)의 발현 수준 변화를 도 3a 및 도 3b에 나타내었다. 3 × 10 5 cells of primary melanocytes were seeded in a 6-well plate, and 0.5 μM, 1 μM, or 2 μM of 7DG, a P2X7 receptor antagonist, was treated for 30 minutes. After 3 days, hemolysis buffer was added to the cell pellet, followed by centrifugation (4 °C, 10 minutes) at 4 °C for 30 minutes. After transferring only the supernatant to a new ep tube, protein quantification was performed using a BCA assay. Electrophoresis was carried out on a 10% polyacrylamide gel and transferred to a nitrocellulose membrane. Anti-tyrosinase and membrane were reacted overnight at 4 ° C., bands were identified using an ECL kit, glycoprotein (gp100) in melanocytes, a protein involved in melanin synthesis, Changes in the expression levels of microphthalmia-associated transcriptian factor (MITF) and tyrosinase are shown in FIGS. 3a and 3b.
실험 결과, 도 3b에서 보는 바와 같이 멜라닌 세포에 7DG 화합물을 농도 별로 처리한 결과 멜라노좀에 특이한 당단백질인 gp100에 반응함과 동시에 7DG 농도가 증가할수록 멜라닌 합성 촉진 인자인 타이로시나아제의 발현 수준이 현저히 감소한 것을 확인할 수 있었다. As a result of the experiment, as shown in FIG. 3B, as a result of treating melanocytes with 7DG compounds at each concentration, the expression level of tyrosinase, a melanin synthesis promoting factor, responds to gp100, a glycoprotein specific to melanosomes, and increases as the 7DG concentration increases. It was found that this markedly decreased.
추가적으로, 타이로시나아제 효소 활성을 보기 위하여 6 웰 플레이트에 1 차 멜라닌 세포(primary melanocytes) 3 x 105 개 세포를 시딩하고, 7DG를 농도 별로 0.5 μM, 1 μM 또는 2 μM을 처리하고 3 일 후 지모그래피 분석(zymography assay)을 수행하여 그 결과를 도 4a 및 도 4b에 나타내었다. 상기 도면을 참조하면, 7DG 화합물을 처리하는 경우 농도에 따라 티로시나아제 효소의 활성 수준이 감소하는 것을 확인할 수 있었다. 종합하면, 본 발명에 따른 7DG 화합물이 타이로시나아제의 발현 및 활성 수준을 감소시키는 것을 통하여 색소 침착에 기인한 색소 질환의 치료제로서 효과가 있을 것임을 시사한다.Additionally, 3 × 10 5 cells of primary melanocytes were seeded in a 6-well plate to see the activity of tyrosinase enzyme, and 7DG was treated with 0.5 μM, 1 μM or 2 μM for each concentration, and 3 days Post zymography analysis (zymography assay) was performed and the results are shown in FIGS. 4a and 4b. Referring to the figure, it was confirmed that the activity level of the tyrosinase enzyme was reduced according to the concentration when the 7DG compound was treated. Taken together, it is suggested that the 7DG compound according to the present invention will be effective as a therapeutic agent for pigment diseases caused by pigmentation through reducing the expression and activity level of tyrosinase.
실시예 3: 7DG 화합물의 멜라닌 형성 억제 효과(2) - 멜라닌 수준 측정Example 3: Melanin Formation Inhibitory Effect of 7DG Compound (2) - Measurement of Melanin Level
7DG 화합물의 멜라닌 합성 억제 효과를 확인하기 위해 6 웰 플레이트에 1 차 멜라닌 세포 3 x 105 개를 시딩하고, 7DG 화합물을 0.5 μM, 1 μM 또는 2 μM을 처리한 뒤 4 일 동안 배양한 후 수득한 세포를 세포 용해 버퍼를 이용하여 용해시킨 뒤, 세포 펠렛(pellet)에 1N 염화나트륨(NaOH)을 넣고 60 ℃에서 2 시간 동안 용해한 뒤, 405 nm의 흡광도에서 ELISA를 이용하여 멜라닌 함량을 측정하여 도 5a 및 도 5b에 나타내었다. In order to confirm the melanin synthesis inhibitory effect of the 7DG compound, 3 × 10 5 primary melanocytes were seeded in a 6-well plate, treated with 0.5 μM, 1 μM or 2 μM of the 7DG compound, and then cultured for 4 days. After lysing one cell using a cell lysis buffer, 1N sodium chloride (NaOH) was added to the cell pellet, lysis was performed at 60 ° C for 2 hours, and then the melanin content was measured using ELISA at an absorbance of 405 nm. 5a and 5b.
도 5a 및 도 5b에서 보는 바와 같이, 멜라닌 세포에 7DG 화합물을 처리하자 멜라닌 함량이 현저히 감소하는 것을 확인할 수 있었다. 이를 통하여 본 발명에 따른 7DG 화합물은 멜라닌 합성을 효과적으로 억제하여 피부 미백 효과가 있을 것임을 알 수 있다. As shown in Figures 5a and 5b, it was confirmed that the melanin content significantly decreased when the 7DG compound was treated with melanocytes. Through this, it can be seen that the 7DG compound according to the present invention will have a skin whitening effect by effectively inhibiting melanin synthesis.
실시예 4: 7DG 화합물의 멜라닌 형성 억제 효과(3) -멜라닌 수준 측정Example 4: Melanin Formation Inhibitory Effect of 7DG Compound (3) - Measurement of Melanin Level
7DG 화합물의 실제 사람 피부 조직에서의 멜라닌 합성 억제 효과를 확인하기 위해 수득한 피부 조직에 UVB(30 mJ/cm2)를 3 일 동안 총 90 mJ/cm2를 조사하였고, 에탄올에 녹인 7DG 화합물의 처리 후 8 일째 멕사미터(Mexameter, Germany)를 이용한 색소 침착 부위의 피부 멜라닌 평가를 수행하였다. 멕사미터로 시험 부위의 피부 멜라닌을 각각 3회 측정한 후 평균값을 구하여 평가하였으며, 그 결과를 하기 표 1에 나타내었다. In order to confirm the melanin synthesis inhibitory effect of the 7DG compound in actual human skin tissue, the obtained skin tissue was irradiated with UVB (30 mJ/cm 2 ) for 3 days at a total of 90 mJ/cm 2 , and the 7DG compound dissolved in ethanol On the 8th day after the treatment, skin melanin was evaluated in the pigmentation area using a Mexameter (Mexameter, Germany). After measuring the skin melanin of the test site three times with a meximeter, the average value was evaluated and evaluated, and the results are shown in Table 1 below.
1회1 | 2회Episode 2 | 3회3rd time | 평균average | 표준편차(SD)standard deviation (SD) | |||
1One | controlcontrol | 152152 | 159159 | 145145 | 152152 | 77 | |
22 | UVBUVB | 294294 | 276276 | 275275 | 281.67281.67 | 10.6910.69 | |
33 | UVB + 7DG(2μM)UVB + 7DG (2μM) | 223223 | 217217 | 217217 | 219219 | 3.463.46 | |
44 | UVB + 7DG(5μM)UVB + 7DG (5μM) | 217217 | 213213 | 210210 | 213.33213.33 | 3.513.51 |
흡광 원리에 기초하여 특수한 탐침이 정해진 세 가지 파장의 빛을 방출하고 피부에서 반사된 빛을 측정함으로써 멜라닌의 양을 측정하였으며, 피부 멜라닌의 양이 적을수록 측정값이 낮아지며 피부 멜라닌이 개선됨을 의미한다. 상기 표 1에서도 알 수 있듯이, 7DG 화합물의 처리 후 8 일 만에 3 번 및 4 번 피부 조직에서의 멜라닌 측정값이 2 번과 비교하여 약 25 % 감소한 것을 확인할 수 있었다. 또한, 도 6b는 7 DG 처리 후 8 일 후에 촬영된 사진이며, 육안으로도 확연히 피부톤이 개선된 것을 알 수 있어 피부 멜라닌 개선에 도움을 주는 것을 검증할 수 있었다.Based on the principle of light absorption, a special probe emits light of three predetermined wavelengths and measures the amount of melanin by measuring the light reflected from the skin. . As can be seen in Table 1, it was confirmed that the measured melanin values in skin tissues No. 3 and No. 4 decreased by about 25% after 8 days of treatment with the 7DG compound compared to No. 2. In addition, FIG. 6B is a photograph taken 8 days after 7 DG treatment, and it can be seen that the skin tone is clearly improved with the naked eye, confirming that it helps to improve skin melanin.
실시예 5: 7DG 화합물의 멜라닌 형성 억제 효과(4) -멜라닌 수준 측정Example 5: Melanin Formation Inhibitory Effect of 7DG Compound (4) - Measurement of Melanin Level
색소 침착의 치료 효과를 확인하고자, 실제 피부 조직에 적용하여 형광 멜라닌을 확인하는 실험을 추가로 수행하였다. 피부 조직을 4 mm 펀치로 수득한 후 조직 배양하였으며, 조직 위에 UVB(30 mJ/cm2)를 3 일 동안 노출시켰고, 에탄올에 녹인 7DG 화합물을 처리한 후 5 일째 프로즌 블록(frozen block)을 만들고 Fontana-massone 염색 키트를 이용하여 피부 조직 세포의 멜라닌을 염색한 후 현미경으로 결과를 도 7에 나타내었다. In order to confirm the therapeutic effect of pigmentation, an experiment to confirm fluorescent melanin by applying to actual skin tissue was additionally performed. Skin tissue was obtained with a 4 mm punch and then tissue cultured, UVB (30 mJ/cm 2 ) was exposed on the tissue for 3 days, and a frozen block was made on the 5th day after treatment with a 7DG compound dissolved in ethanol. After staining melanin of skin tissue cells using a Fontana-massone staining kit, the results are shown in FIG. 7 under a microscope.
도 7을 참조하면, UVB에 노출되어 멜라닌이 증가된 피부 조직에 7DG 화합물을 처리할 경우 멜라닌 세포의 분포가 현저히 감소한 것을 확인할 수 있다. 이는 곧 7DG 화합물의 멜라닌 억제 효과를 나타내는 것이므로 색소 침착에 기인한 증상을 완화 또는 개선시켜주는 제제로서 다양하게 활용될 수 있을 것으로 기대된다. Referring to FIG. 7 , it can be seen that the distribution of melanocytes is significantly reduced when the 7DG compound is treated with skin tissue in which melanin is increased due to exposure to UVB. Since this shows the melanin inhibitory effect of the 7DG compound, it is expected that it can be used in various ways as an agent for alleviating or improving symptoms caused by pigmentation.
이상에서 본 발명의 실시예에 대하여 상세하게 설명하였지만 본 발명의 권리범위는 이에 한정되는 것은 아니고, 청구범위에 기재된 본 발명의 기술적 사상을 벗어나지 않는 범위 내에서 다양한 수정 및 변형이 가능하다는 것은 당 기술분야의 통상의 지식을 가진 자에게는 자명할 것이다.Although the embodiments of the present invention have been described in detail above, the scope of the present invention is not limited thereto, and various modifications and variations are possible without departing from the technical spirit of the present invention described in the claims. It will be obvious to those skilled in the art.
본 발명에 따른 조성물은 인체에 독성을 일으키지 않으면서도 멜라닌 생성 및 합성을 효과적으로 억제하여 피부 미백 효과가 뛰어나며, 색소 침착에 기인한 기미, 주근깨, 노인성 색소반, 잡티, 모반 또는 일광흑색증(solar lentigines) 등의 색소 질환의 예방, 개선 또는 치료에 매우 효과적으로 사용될 수 있다.The composition according to the present invention has an excellent skin whitening effect by effectively inhibiting the production and synthesis of melanin without causing toxicity to the human body, and is effective against melasma, freckles, senile pigment spots, blemishes, birthmarks or solar lentigines caused by pigmentation. ) can be used very effectively for the prevention, improvement, or treatment of pigmented diseases.
Claims (18)
- 하기 화학식 1로 표시되는 7-데스아세톡시-6,7-디하이드로게두닌(7-Desacetoxy-6,7-dehydrogedunin; 7DG) 또는 이의 약제학적으로 허용 가능한 염을 유효 성분으로 포함하는, 색소 질환의 예방 또는 치료용 약학 조성물:Pigmented diseases comprising 7-Desacetoxy-6,7-dehydrogedunin (7DG) or a pharmaceutically acceptable salt thereof represented by Formula 1 below as an active ingredient A pharmaceutical composition for the prevention or treatment of:[화학식 1][Formula 1]
- 제 1항에 있어서,According to claim 1,상기 조성물은 멜라닌 생성을 억제하는 것인, 약학 조성물.Wherein the composition inhibits melanin production, the pharmaceutical composition.
- 제 1항에 있어서,According to claim 1,상기 색소 질환은 멜라닌의 과도한 증가에 기인한 질환인, 약학 조성물. The pigment disease is a disease caused by an excessive increase in melanin, the pharmaceutical composition.
- 제 3항에 있어서,According to claim 3,상기 색소 질환은 기미, 주근깨, 검버섯, 잡티, 노인성 색소반, 표피 멜라닌세포성 병변(Epidermal melanocytic lesion), 밀크커피 반점(Cafe's au lait macules), 모반, 베커 모반(Becker's Nevus), 반문상 모반(Nevus Spilus), 흑자(Lentigines), 흑색점, 진피 멜라닌세포성 병변(Dermal melanocytic lesions), 몽고반(Mongolian spot), 오타 모반(Nevus of Ota), 후천성 양측성 오타 모반양 반(Acquired bilateral nevus of Ota-like macules), 이토 모반(Nevus of Ito), 청색 모반(Blue nevus), 멜라닌형성세포성 모반(Melanocytic nevus), 경계 모반(Junctional nevus), 복합 모반(Compound nevus), 진피내 모반(Intradermal nevus), 운륜 모반(Halo nevus), 선천성 멜라닌세포성 모반(Congenital nevocytic nevus), 스피츠 모반(Spitz nevus), 이형성 모반(Dysplastic nevus), 임신성 갈색반(gravidic chloasma), 흑색종(Melanoma), 악성 흑자 흑색종(Lentigo maligna melanoma), 표재 확장성 흑색종(Superficial spreading melanoma), 선단 흑자성 흑색종(Acral lentiginous melanoma), 결절성 흑색종(Nodular melanoma), 색소성 기저세포암(pigment basal cell carcinoma), 색소성 피부섬유종(dermatofibromas), 색소성 피부낭종(dermoid cyst), 색소성 켈로이드(keloid), 일광 흑색증(solar lentigines), 색소성 편평태선(Lichen planus), 색소성 접촉피부염(Contact dermatitis), 자외선에 의한 색소 침착, 약물에 의한 색소 침착, 상처로 인한 색소 침착, 염증 후 색소 침착, 색소성 각질가시세포종(keratoacanthomas) 및 릴 흑피증(Riehl's melanosis)으로 이루어진 군에서 선택된 적어도 하나인, 약학 조성물.The pigmented diseases include melasma, freckles, age spots, blemishes, senile pigment spots, epidermal melanocytic lesions, Cafe's au lait macules, nevus, Becker's nevus, and birthmark nevus ( Nevus Spilus, Lentigines, lentigo, dermal melanocytic lesions, Mongolian spot, Nevus of Ota, Acquired bilateral nevus of Ota -like macules), Nevus of Ito, Blue nevus, Melanocytic nevus, Junctional nevus, Compound nevus, Intradermal nevus ), halo nevus, congenital nevocytic nevus, Spitz nevus, dysplastic nevus, gravidic chloasma, melanoma, lentigo malignant Lentigo maligna melanoma, superficial spreading melanoma, acral lentiginous melanoma, nodular melanoma, pigment basal cell carcinoma, Pigmented dermatofibromas, pigmented dermoid cyst, pigmented keloid, solar lentigines, lichen planus pigmented, contact dermatitis pigmented, pigmentation by ultraviolet rays, pigmentation by drugs, At least one selected from the group consisting of pigmentation due to wounds, pigmentation after inflammation, pigmented keratoacanthomas, and Riehl's melanosis, a pharmaceutical composition.
- 하기 화학식 1로 표시되는 7-데스아세톡시-6,7-디하이드로게두닌(7-Desacetoxy-6,7-dehydrogedunin; 7DG) 또는 이의 약제학적으로 허용 가능한 염을 유효 성분으로 포함하는, 색소 질환의 예방 또는 개선용 식품 조성물:Pigmented diseases comprising 7-Desacetoxy-6,7-dehydrogedunin (7DG) or a pharmaceutically acceptable salt thereof represented by Formula 1 below as an active ingredient Food composition for prevention or improvement of:[화학식 1][Formula 1]
- 제 5항에 있어서,According to claim 5,상기 조성물은 멜라닌 생성을 억제하는 것인, 식품 조성물.The composition is to inhibit melanin production, food composition.
- 제 5항에 있어서,According to claim 5,상기 색소 질환은 멜라닌의 과도한 증가에 기인한 질환인, 식품 조성물.The pigment disease is a disease caused by an excessive increase in melanin, food composition.
- 제 7항에 있어서,According to claim 7,상기 색소 질환은 기미, 주근깨, 검버섯, 잡티, 노인성 색소반, 표피 멜라닌세포성 병변(Epidermal melanocytic lesion), 밀크커피 반점(Cafe's au lait macules), 모반, 베커 모반(Becker's Nevus), 반문상 모반(Nevus Spilus), 흑자(Lentigines), 흑색점, 진피 멜라닌세포성 병변(Dermal melanocytic lesions), 몽고반(Mongolian spot), 오타 모반(Nevus of Ota), 후천성 양측성 오타 모반양 반(Acquired bilateral nevus of Ota-like macules), 이토 모반(Nevus of Ito), 청색 모반(Blue nevus), 멜라닌형성세포성 모반(Melanocytic nevus), 경계 모반(Junctional nevus), 복합 모반(Compound nevus), 진피내 모반(Intradermal nevus), 운륜 모반(Halo nevus), 선천성 멜라닌세포성 모반(Congenital nevocytic nevus), 스피츠 모반(Spitz nevus), 이형성 모반(Dysplastic nevus), 임신성 갈색반(gravidic chloasma), 흑색종(Melanoma), 악성 흑자 흑색종(Lentigo maligna melanoma), 표재 확장성 흑색종(Superficial spreading melanoma), 선단 흑자성 흑색종(Acral lentiginous melanoma), 결절성 흑색종(Nodular melanoma), 색소성 기저세포암(pigment basal cell carcinoma), 색소성 피부섬유종(dermatofibromas), 색소성 피부낭종(dermoid cyst), 색소성 켈로이드(keloid), 일광 흑색증(solar lentigines), 색소성 편평태선(Lichen planus), 색소성 접촉피부염(Contact dermatitis), 자외선에 의한 색소 침착, 약물에 의한 색소 침착, 상처로 인한 색소 침착, 염증 후 색소 침착, 색소성 각질가시세포종(keratoacanthomas) 및 릴 흑피증(Riehl's melanosis)으로 이루어진 군에서 선택된 적어도 하나인, 식품 조성물.The pigmented diseases include melasma, freckles, age spots, blemishes, senile pigment spots, epidermal melanocytic lesions, Cafe's au lait macules, nevus, Becker's nevus, and birthmark nevus ( Nevus Spilus, Lentigines, lentigo, dermal melanocytic lesions, Mongolian spot, Nevus of Ota, Acquired bilateral nevus of Ota -like macules), Nevus of Ito, Blue nevus, Melanocytic nevus, Junctional nevus, Compound nevus, Intradermal nevus ), halo nevus, congenital melanocytic nevus, Spitz nevus, dysplastic nevus, gravidic chloasma, melanoma, lentigo malignant Lentigo maligna melanoma, superficial spreading melanoma, acral lentiginous melanoma, nodular melanoma, pigment basal cell carcinoma, Pigmented dermatofibromas, pigmented dermoid cyst, pigmented keloid, solar lentigines, lichen planus pigmented, contact dermatitis pigmented, pigmentation by ultraviolet rays, pigmentation by drugs, Pigmentation due to wounds, pigmentation after inflammation, pigmented keratoacanthomas, and at least one selected from the group consisting of Riehl's melanosis, a food composition.
- 하기 화학식 1로 표시되는 7-데스아세톡시-6,7-디하이드로게두닌(7-Desacetoxy-6,7-dehydrogedunin; 7DG) 또는 이의 화장품학적으로 허용 가능한 염을 유효 성분으로 포함하는, 색소 질환의 예방 또는 개선용 화장료 조성물:7-Desacetoxy-6,7-dehydrogedunin represented by Formula 1 below (7-Desacetoxy-6,7-dehydrogedunin; 7DG) or a cosmetically acceptable salt thereof as an active ingredient, pigmented disease A cosmetic composition for the prevention or improvement of:[화학식 1][Formula 1]
- 제 9항에 있어서,According to claim 9,상기 조성물은 멜라닌 생성을 억제하는 것인, 화장료 조성물.The composition is to inhibit melanin production, a cosmetic composition.
- 제 9항에 있어서,According to claim 9,상기 색소 질환은 멜라닌의 과도한 증가에 기인한 질환인, 화장료 조성물.The pigment disease is a disease caused by an excessive increase in melanin, a cosmetic composition.
- 제 11항에 있어서,According to claim 11,상기 색소 질환은 기미, 주근깨, 검버섯, 잡티, 노인성 색소반, 표피 멜라닌세포성 병변(Epidermal melanocytic lesion), 밀크커피 반점(Cafe's au lait macules), 모반, 베커 모반(Becker's Nevus), 반문상 모반(Nevus Spilus), 흑자(Lentigines), 흑색점, 진피 멜라닌세포성 병변(Dermal melanocytic lesions), 몽고반(Mongolian spot), 오타 모반(Nevus of Ota), 후천성 양측성 오타 모반양 반(Acquired bilateral nevus of Ota-like macules), 이토 모반(Nevus of Ito), 청색 모반(Blue nevus), 멜라닌형성세포성 모반(Melanocytic nevus), 경계 모반(Junctional nevus), 복합 모반(Compound nevus), 진피내 모반(Intradermal nevus), 운륜 모반(Halo nevus), 선천성 멜라닌세포성 모반(Congenital nevocytic nevus), 스피츠 모반(Spitz nevus), 이형성 모반(Dysplastic nevus), 임신성 갈색반(gravidic chloasma), 흑색종(Melanoma), 악성 흑자 흑색종(Lentigo maligna melanoma), 표재 확장성 흑색종(Superficial spreading melanoma), 선단 흑자성 흑색종(Acral lentiginous melanoma), 결절성 흑색종(Nodular melanoma), 색소성 기저세포암(pigment basal cell carcinoma), 색소성 피부섬유종(dermatofibromas), 색소성 피부낭종(dermoid cyst), 색소성 켈로이드(keloid), 일광 흑색증(solar lentigines), 색소성 편평태선(Lichen planus), 색소성 접촉피부염(Contact dermatitis), 자외선에 의한 색소 침착, 약물에 의한 색소 침착, 상처로 인한 색소 침착, 염증 후 색소 침착, 색소성 각질가시세포종(keratoacanthomas) 및 릴 흑피증(Riehl's melanosis)으로 이루어진 군에서 선택된 적어도 하나인, 화장료 조성물.The pigmented diseases include melasma, freckles, age spots, blemishes, senile pigment spots, epidermal melanocytic lesions, Cafe's au lait macules, nevus, Becker's nevus, and birthmark nevus ( Nevus Spilus, Lentigines, lentigo, dermal melanocytic lesions, Mongolian spot, Nevus of Ota, Acquired bilateral nevus of Ota -like macules), Nevus of Ito, Blue nevus, Melanocytic nevus, Junctional nevus, Compound nevus, Intradermal nevus ), halo nevus, congenital melanocytic nevus, Spitz nevus, dysplastic nevus, gravidic chloasma, melanoma, lentigo malignant Lentigo maligna melanoma, superficial spreading melanoma, acral lentiginous melanoma, nodular melanoma, pigment basal cell carcinoma, Pigmented dermatofibromas, pigmented dermoid cyst, pigmented keloid, solar lentigines, lichen planus pigmented, contact dermatitis pigmented, pigmentation by ultraviolet rays, pigmentation by drugs, At least one cosmetic composition selected from the group consisting of pigmentation due to wounds, pigmentation after inflammation, pigmented keratoacanthomas, and Riehl's melanosis.
- 하기 화학식 1로 표시되는 7-데스아세톡시-6,7-디하이드로게두닌(7-Desacetoxy-6,7-dehydrogedunin; 7DG) 또는 이의 화장품학적으로 허용 가능한 염을 유효 성분으로 포함하는, 미백용 화장료 조성물:7-Desacetoxy-6,7-dehydrogedunin (7-Desacetoxy-6,7-dehydrogedunin; 7DG) represented by Formula 1 or a cosmetically acceptable salt thereof as an active ingredient for whitening Cosmetic composition:[화학식 1][Formula 1]
- 제 13항에 있어서,According to claim 13,상기 조성물은 티로시나제 활성 억제 또는 멜라닌 합성을 억제하는 것인, 화장료 조성물.The composition is to inhibit tyrosinase activity inhibition or melanin synthesis, a cosmetic composition.
- 제 13항에 있어서,According to claim 13,상기 조성물은 용액, 외용 연고, 크림, 폼, 영양 화장수, 유연 화장수, 팩, 유연수, 유액, 메이크업 베이스, 에센스, 비누, 액체 세정료, 입욕제, 선 스크린 크림, 선 오일, 현탁액, 유탁액, 페이스트, 겔, 로션, 파우더, 비누, 계면 활성제-함유 클렌징, 오일, 분말 파운데이션, 유탁액 파운데이션, 왁스 파운데이션, 패취 및 스프레이로 이루어진 군으로부터 선택되는 적어도 하나의 제형을 가지는 것인, 화장료 조성물.The composition is a solution, external ointment, cream, foam, nourishing lotion, softening lotion, pack, softening water, emulsion, makeup base, essence, soap, liquid cleanser, bath additive, sunscreen cream, sun oil, suspension, emulsion, paste , A cosmetic composition having at least one formulation selected from the group consisting of gel, lotion, powder, soap, surfactant-containing cleansing, oil, powder foundation, emulsion foundation, wax foundation, patch and spray.
- 하기 화학식 1로 표시되는 7-데스아세톡시-6,7-디하이드로게두닌(7-Desacetoxy-6,7-dehydrogedunin; 7DG) 또는 이의 화장품학적으로 허용 가능한 염을 유효 성분으로 포함하는, 미백용 의약외품 조성물:7-Desacetoxy-6,7-dehydrogedunin (7-Desacetoxy-6,7-dehydrogedunin; 7DG) represented by Formula 1 or a cosmetically acceptable salt thereof as an active ingredient for whitening Quasi-drug composition:[화학식 1][Formula 1]
- 제 16항에 있어서,According to claim 16,상기 조성물은 멜라닌 생성을 억제하는 것인, 의약외품 조성물.The composition is to inhibit melanin production, quasi-drug composition.
- 제 16항에 있어서,According to claim 16,상기 조성물은 용액, 외용 연고, 크림, 폼, 영양 화장수, 유연 화장수, 팩, 유연수, 유액, 메이크업 베이스, 에센스, 비누, 액체 세정료, 입욕제, 선 스크린 크림, 선 오일, 현탁액, 유탁액, 페이스트, 겔, 로션, 파우더, 비누, 계면 활성제-함유 클렌징, 오일, 분말 파운데이션, 유탁액 파운데이션, 왁스 파운데이션, 패취 및 스프레이로 이루어진 군으로부터 선택되는 적어도 하나의 제형을 가지는 것인, 의약외품 조성물.The composition is a solution, external ointment, cream, foam, nourishing lotion, softening lotion, pack, softening water, emulsion, makeup base, essence, soap, liquid cleanser, bath additive, sunscreen cream, sun oil, suspension, emulsion, paste , Gel, lotion, powder, soap, surfactant-containing cleansing, oil, powder foundation, emulsion foundation, wax foundation, having at least one formulation selected from the group consisting of patches and sprays, quasi-drug composition.
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WO1997035998A1 (en) * | 1996-03-28 | 1997-10-02 | Trustees Of Boston University | Methods of modulating melanin synthesis |
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WO1997035998A1 (en) * | 1996-03-28 | 1997-10-02 | Trustees Of Boston University | Methods of modulating melanin synthesis |
Non-Patent Citations (4)
Title |
---|
CHA SANG BOK, NAM YOUNG CHO, MI YUN YOON, HYE WON LIM, KYOUNG WON KIM, YOUNG MI PARK, JI YUN LEE, JIN HEE LEE, CHANG JONG KIM, SAN: "Effects of Protein Kinase Inhibitors on Melanin Production in B16 Melanoma Cells Stimulated via Cyclic AMP-dependent Pathway", JOURNAL OF THE PHARMACEUTICAL SOCIETY OF KOREA, vol. 47, no. 1, pages 31 - 36, XP093035335 * |
HETT ERIK C, SLATER LOUISE H, MARK KEVIN G, KAWATE TOMOHIKO, MONKS BRIAN G, STUTZ ANDREA, LATZ EICKE, HUNG DEBORAH T: "Chemical genetics reveals a kinase-independent role for protein kinase R in pyroptosis", NATURE CHEMICAL BIOLOGY, NATURE PUBLISHING GROUP US, NEW YORK, vol. 9, no. 6, 1 June 2013 (2013-06-01), New York, pages 398 - 405, XP093035330, ISSN: 1552-4450, DOI: 10.1038/nchembio.1236 * |
JEON HWANG-JU, KIM KYEONGNAM, KIM CHAEEUN, KIM MYOUNG-JIN, KIM TAE-OH, LEE SUNG-EUN: "Molecular Mechanisms of Anti-Melanogenic Gedunin Derived from Neem Tree (Azadirachta indica) Using B16F10 Mouse Melanoma Cells and Early-Stage Zebrafish", PLANTS, vol. 10, no. 2, 9 February 2021 (2021-02-09), pages 330, XP093035337, DOI: 10.3390/plants10020330 * |
PARK SUJIN: "Discovery of natural compounds with anti-melanogenic effect through targeting ATP-P2X7 axis", MASTER'S THESIS, THE GRADUATE SCHOOL OF YONSEI UNIVERSITY, DEPARTMENT OF MEDICINE, 1 December 2021 (2021-12-01), XP093035340, Retrieved from the Internet <URL:https://ir.ymlib.yonsei.ac.kr/handle/22282913/189665> [retrieved on 20230328] * |
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