KR101777368B1 - Composition for skin-whitener containing extract of china rose - Google Patents
Composition for skin-whitener containing extract of china rose Download PDFInfo
- Publication number
- KR101777368B1 KR101777368B1 KR1020150110450A KR20150110450A KR101777368B1 KR 101777368 B1 KR101777368 B1 KR 101777368B1 KR 1020150110450 A KR1020150110450 A KR 1020150110450A KR 20150110450 A KR20150110450 A KR 20150110450A KR 101777368 B1 KR101777368 B1 KR 101777368B1
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- KR
- South Korea
- Prior art keywords
- skin
- extract
- skin whitening
- lotion
- cosmetic composition
- Prior art date
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Classifications
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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
- A61K8/96—Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution
- A61K8/97—Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution from algae, fungi, lichens or plants; from derivatives thereof
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/73—Rosaceae (Rose family), e.g. strawberry, chokeberry, blackberry, pear or firethorn
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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
- A61K8/02—Cosmetics or similar toiletry preparations characterised by special physical form
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- 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
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Abstract
본 발명은 월계화 추출물을 유효성분으로 함유하는 피부 미백 화장료 조성물에 관한 것으로 멜라닌 색소의 생성을 억제하고 타이로시나아제 유전자 발현을 억제하여 뛰어난 색소 침착 저해 효과를 나타내므로 피부 미백에 유용하게 사용될 수 있다.The present invention relates to a skin whitening cosmetic composition containing an extract of Laureliaceae as an active ingredient and can be usefully used for skin whitening because it inhibits the production of melanin pigment and suppresses expression of tyrosinase gene and exhibits excellent inhibitory effect on pigment deposition .
Description
본 발명은 피부 미백에 유용하게 사용될 수 있는 월계화 추출물을 유효성분으로 함유하는 피부 미백 화장료 조성물, 및 피부 색소 침착 질환의 치료 및 예방용 약학적 조성물에 관한 것이다.The present invention relates to a skin whitening cosmetic composition containing as an active ingredient an extract of Laurel on White which can be usefully used for skin whitening, and a pharmaceutical composition for treating and preventing skin pigmentation diseases.
멜라닌 색소는 자외선을 흡수하여 자외선에 의한 손상으로부터 피부 기관을 보호하는 역할을 수행하며, 피부 내에 발생하는 유해산소나 라디칼(free radical)등의 유해 물질을 제거하는 역할을 수행하여 피부를 보호해주는 역할을 한다.Melanin pigment absorbs ultraviolet rays and protects skin organs from damage caused by ultraviolet rays. It protects skin by removing harmful substances such as harmful oxygen and free radicals generated in skin .
이와 같은 멜라닌 색소의 유용한 역할에도 불구하고, 멜라닌 색소가 자외선, 호르몬 변화, 염증, 또는 약제 등 여러 가지 환경적 요인에 의해 과도하게 합성되어 피부에 침착하면, 피부 색소 침착 질환을 일으켜 피부 미용에 악영향을 미치고, 더 나아가 피부암의 원인이 되기도 한다.Despite the useful role of the melanin pigment, when melanin pigment is overly synthesized by various environmental factors such as ultraviolet ray, hormone change, inflammation, or medicines and is deposited on the skin, it causes skin pigmentation disease and adversely affects skin beauty And, furthermore, it causes skin cancer.
이러한 멜라닌 색소에 의해 유발되는 피부 색소 침착 질환은 현대인의 미의 기준인 미백을 해치는 요소로 인식되어, 건강은 물론이고, 미용적인 측면에서 다양한 해결 방법이 연구되고 있다.Skin pigmentation disease caused by melanin pigment is recognized as a factor that hinders whitening, which is a standard of modern beauty, and various solutions are being studied in terms of health as well as cosmetics.
현재 피부 색소 침착 치료 방법으로는 하이드로퀴논 표백제, 비타민 A 연고, 국소 스테로이드 연고, 비타민 C, 글라이콜릭산, 아젤레익산 등을 혼합하여 사용하면서, 고농도의 비타민 C를 침투시키는 전기영동치료를 정기적으로 시행하는 치료 방법이 있으며, 최근에는 TCA나 글라이콜릭산을 이용한 박피술을 국소 치료와 병행하여 주기적으로 시행하는 방법도 많이 이용되고 있다.Currently, skin pigmentation treatment methods include hydroquinone bleach, vitamin A ointment, topical steroid ointment, vitamin C, glycolic acid, and azelaic acid, while using a mixture of high concentrations of vitamin C and electrophoresis . Recently, TCA or glyceral acid - based dressings have been used in many cases with local treatment.
그러나, 현재까지 피부 색소 침착 질환을 완벽하게 치료하는 방법은 없으며, 어떤 치료 방법을 사용하더라도 쉽게 재발할 가능성이 있다. 따라서, 피부의 멜라닌 생성 기전을 근본적으로 이해하고 이를 바탕으로 멜라닌 색소 생성을 억제할 수 있는 새로운 치료제의 개발이 요구된다.However, until now, there is no perfect way to treat skin pigmentation disease, and there is a possibility of recurrence easily with any treatment method. Therefore, it is required to develop a new therapeutic agent capable of inhibiting the production of melanin pigment based on the fundamental understanding of the mechanism of skin melanogenesis.
한편, 멜라닌 색소는 멜라노사이트(melanocyte) 세포 내의 멜라노좀이라는 소포체에서 타이로시나제(Tyrosinase)라는 효소에 의해 티로신이 도파(DOPA)를 거쳐 도파퀴논(DOPA quinone)으로 전환되고, 도파퀴논으로부터 자동 산화 반응과 효소 반응을 통하여 도파크롬(DOPA chrome)을 거쳐 합성된다.On the other hand, the melanin pigment is converted from tyrosinase (DOPA) to dopaquinone (DOPA quinone) by an enzyme called tyrosinase in the melanocyte endoplasmic reticulum in the melanocyte cell, It is synthesized through DOPA chrome through oxidation and enzymatic reaction.
이렇게 합성된 멜라닌 색소는 주변의 케라틴 세포(keratinocyte)로 전달 분배되어 피부에서 흑갈색 색소 침착 또는 피부 색소 침착 질환이라는 표현형으로 드러나게 된다.The synthesized melanin pigment is transferred and distributed to the surrounding keratinocyte and becomes a phenotype called dark brown pigmentation or skin pigmentation disease in the skin.
따라서, 멜라닌 색소 합성을 억제하는 것이야말로 피부 색소 침착 질환을 치료 및 예방할 수 있는 가장 근본적인 방법이 되는 것이며, 상기 멜라닌 색소를 합성하는 멜라노사이트 세포에 대해 특이적으로 작용하는 독성 물질이나, 멜라닌 색소 대사합성 과정에 핵심적으로 관여하는 타이로시나아제 유전자의 발현을 조절하여 피부 미백 및 피부 색소 침착 질환의 치료를 달성하고자 하는 연구가 활발하게 진행되고 있다.Therefore, inhibiting the synthesis of melanin pigment is the most fundamental method for treating and preventing skin pigmentation disease, and it is a toxic substance specifically acting on melanocyte cells synthesizing the melanin pigment or melanin pigment metabolism Studies have been actively conducted to achieve skin whitening and skin pigmentation diseases by regulating the expression of tyrosinase gene, which is involved in the synthesis process.
현재까지 개발된 피부 색소 침착 질환의 치료제로는 파라-메톡시페놀(p-methoxyphenol), 하이드로퀴논(hydroquinone), 코지산(kojic acid), 알부틴(arbutin) 등이 사용되고 있으나, 이들은 활성이 약하거나 색소 세포의 변성 또는 치사를 일으킬 수 있으며, 세포 본래의 기능을 손상시키는 등의 단점이 있다. P-methoxyphenol, hydroquinone, kojic acid, arbutin, etc. have been used to treat skin pigmentation diseases so far, but they are weakly active It may cause denaturation or lethality of the pigment cells, and the original function of the cells is impaired.
한편, 멜라닌 생성 억제를 목적으로 비타민 C 및 그 유도체 등이 사용되고 있으나, 이들 또한 저해활성이 낮다는 단점을 가지고 있다.On the other hand, vitamin C and its derivatives and the like have been used for the purpose of inhibiting melanin production, but these also have a disadvantage of low inhibitory activity.
이들 치료제 외에 천연물, 특히 식물 중에서 미백 활성 성분을 찾기 위한 연구도 계속 이루어져 왔고, 그 중 상백피, 감초, 작약, 계피, 고삼, 갈근, 당귀, 목단피, 반하, 알로에 등의 다수의 식물 추출물 및 생약재 추출물 등이 타이로시나제에 작용하여 멜라닌 생성을 억제한다는 사실이 밝혀졌으나, 이들 역시 안전성 측면에서 화장품이나 의약품에 유효 농도 이상으로 사용하는 데는 많은 문제점이 있고, 아직 뛰어난 효과를 나타내는 천연물은 확인되지 않고 있다.In addition to these therapeutic agents, research on finding whitening active ingredients in natural products, especially plants, has been continued. Among them, many plant extracts and herbal medicine extracts such as alfalfa, licorice, peony, cinnamon, Have been found to act on tyrosinase to inhibit melanin production. However, these have also been found to have a number of problems in terms of their safety from being used in cosmetics or medicines in excess of the effective concentration, have.
따라서, 소량으로도 멜라닌 생합성 저해활성이 우수하고 부작용이 적은 천연물의 개발이 절실히 요구되고 있다.Accordingly, it is urgently required to develop natural products having a small amount of melanin biosynthesis inhibiting activity and a small side effect.
본 발명의 목적은 피부 미백에 유용하게 사용될 수 있는 월계화 추출물을 유효성분으로 함유하는 피부 미백 화장료 조성물을 제공하는데 있다.It is an object of the present invention to provide a skin whitening cosmetic composition containing an extract of Wolgyering, which can be usefully used for skin whitening, as an active ingredient.
또한, 본 발명의 다른 목적은 월계화 추출물을 유효성분으로 함유하는 피부 색소 침착 질환의 치료 및 예방용 약학적 조성물을 제공하는데 있다.Another object of the present invention is to provide a pharmaceutical composition for the treatment and prevention of skin pigmentation diseases, which comprises an extract of Wallaceae as an active ingredient.
상기한 목적을 달성하기 위한 본 발명의 피부 미백 화장료 조성물은 월계화 추출물을 유효성분으로 함유할 수 있다.In order to attain the above object, the skin whitening cosmetic composition of the present invention may contain an extract of Wolgyering, as an active ingredient.
상기 월계화 추출물은 월계화의 꽃잎 및 줄기를 추출한 추출물일 수 있다.The Walukae extract may be an extract obtained by extracting petals and stem of Walukae flower.
상기 월계화 추출물은 월계화의 꽃잎과 줄기를 1 : 0.2 내지 0.9의 중량비로 혼합된 혼합물을 추출한 것일 수 있다.The wollatwaal extract may be obtained by extracting a mixture of petal and stem of Wolgye-gae with a weight ratio of 1: 0.2 to 0.9.
상기 월계화 추출물은 80 내지 120 ℃에서 0.5 내지 3시간 동안 열수 추출된 추출물일 수 있다.The Walukae extract may be a hot-water extract at 80 to 120 ° C for 0.5 to 3 hours.
상기 피부 미백 화장료 조성물은 스킨 소프너, 스킨토너, 아스트린젠트, 로션, 밀크로션, 모이스처 로션, 영양로션, 마사지 크림, 영양크림, 모이스처 크림, 핸드크림, 에센스, 영양에센스, 팩, 비누, 샴푸, 클렌징폼, 클렌징로션, 클렌징크림, 바디로션, 바디클렌저, 유액, 프레스파우더, 루스파우더 및 아이섀도우로 이루어진 군에서 선택된 1종 이상의 제형일 수 있다.The skin whitening cosmetic composition may be used as a skin cosmetic composition for skin such as a skin softener, a skin toner, an astringent, a lotion, a milk lotion, a moisturizing lotion, a nutrition lotion, a massage cream, a nutrition cream, a moisturizing cream, , A cleansing lotion, a cleansing cream, a body lotion, a body cleanser, an emulsion, a press powder, a loose powder, and an eye shadow.
상기 피부 미백은 멜라닌 색소의 생성 억제에 의해 수행될 수 있으며, 또한 상기 피부 미백은 타이로시나아제 유전자 발현 억제에 의해 수행될 수 있다.The skin whitening can be carried out by inhibiting the production of melanin pigment, and the skin whitening can also be carried out by inhibiting tyrosinase gene expression.
또한, 상기한 다른 목적을 달성하기 위한 본 발명의 피부 색소 침착 질환의 치료 및 예방용 약학적 조성물은 월계화 추출물을 유효성분으로 함유할 수 있다.According to another aspect of the present invention, there is provided a pharmaceutical composition for the treatment and prevention of skin pigmentation diseases, which comprises an extract of Wolgyunggae as an active ingredient.
상기 피부 색소 침착 질환은 멜라닌 색소의 합성 증가로 피부에 국소적으로 발생하고, 기미, 주근깨, 흑색점, 모반, 약물에 의한 색소 침착, 염증 후 색소 침착, 및 피부염에서 발생하는 과색소 침착에서 선택된 하나 이상의 질환일 수 있다.The skin pigmentation disease occurs locally in the skin due to increased synthesis of melanin pigment and is selected from hyperpigmentation caused by spots, freckles, black spots, nevi, drug-induced pigmentation, post-inflammatory pigmentation, and dermatitis It may be one or more diseases.
상기 월계화 추출물은 조성물 총 중량 대비 0.001 내지 99.9 중량%로 함유될 수 있다.The wartime extract may be contained in an amount of 0.001 to 99.9% by weight based on the total weight of the composition.
본 발명의 피부 미백 화장료 조성물은 월계화 추출물, 특히 월계화 꽃잎과 줄기를 혼합하여 얻은 추출물을 이용하여 멜라닌 색소 형성에 관여하는 타이로시나아제의 합성을 억제함으로써 멜라닌 색소의 생성을 효과적으로 억제할 수 있다. 이에 따라, 본 발명의 피부 미백 화장료 조성물은 멜라닌 색소의 생성 억제를 통하여 우수한 피부 미백 효과를 가지므로, 피부 미백 화장료 조성물로 유용하게 이용할 수 있다.The skin whitening cosmetic composition of the present invention can effectively inhibit the production of melanin pigment by inhibiting the synthesis of tyrosinase involved in melanin pigment formation by using an extract obtained from a mixture of rosemary extract, especially a mixture of rosemary flower petal and stem. Accordingly, the skin whitening cosmetic composition of the present invention has an excellent skin whitening effect by inhibiting the formation of melanin pigment, and thus can be effectively used as a skin whitening cosmetic composition.
또한, 본 발명의 피부 미백 화장료 조성물은 멜라닌 색소의 생성 억제를 통하여 멜라닌 색소의 과다 생성에 의해 유발된 피부 색소 침착 질환을 치료 및 예방하는데 효과적으로 사용할 수 있다.In addition, the skin whitening cosmetic composition of the present invention can be effectively used for treating and preventing skin pigmentation diseases caused by overproduction of melanin pigment by inhibiting the formation of melanin pigment.
본 발명은 피부 미백에 유용하게 사용될 수 있는 월계화 추출물을 유효성분으로 함유하는 피부 미백 화장료 조성물, 및 피부 색소 침착 질환의 치료 및 예방용 약학적 조성물에 관한 것이다.The present invention relates to a skin whitening cosmetic composition containing as an active ingredient an extract of Laurel on White which can be usefully used for skin whitening, and a pharmaceutical composition for treating and preventing skin pigmentation diseases.
상기 "피부 미백"은 멜라닌 색소의 합성을 저해하여 멜라닌 색소의 피부 침착을 억제 또는 방지하는 것을 의미하며, 피부 색소 침착 질환을 치료 또는 예방하는 것을 포함하는 의미로 사용된다.The above-mentioned "skin whitening" means inhibiting or preventing skin deposition of melanin pigment by inhibiting synthesis of melanin pigment, and is used to include treatment or prevention of skin pigmentation disease.
또한, 상기 "피부 색소 침착 질환"으로는 멜라닌 색소의 합성 증가로 피부에 국소적으로 발생하는 기미, 주근깨, 흑색점, 모반 등의 증상이 있으며, 약물에 의한 색소 침착, 치유된 창상 부위에서 발견되는 염증 후 색소 침착, 또는 피부염의 증상으로 나타나는 과색소 침착 등을 모두 포함하는 의미로 사용된다.
The above-mentioned "skin pigmentation disease" includes symptoms such as spots, freckles, black spots and nevi occurring locally in the skin due to an increase in synthesis of melanin pigment, pigmentation caused by drugs, Or hyperpigmentation after inflammation, or hyperpigmentation, which is a symptom of dermatitis.
이하, 본 발명을 상세하게 설명한다. Hereinafter, the present invention will be described in detail.
본 발명의 피부 미백 화장료 조성물은 월계화 추출물을 유효성분으로 함유한다.The skin whitening cosmetic composition of the present invention contains an extract of Laureliaceae as an active ingredient.
상기 월계화 추출물을 제조하기 위해서는 먼저, 물로 세척하여 이물질이 제거된 월계화의 꽃잎과 줄기에 남아있는 물기를 제거한 후 동결건조기에서 각각 동결건조하여 분말화한다. In order to prepare the ugly extract, firstly, it is washed with water to remove the moisture remaining in the petals and stems of the rosemary which have been removed from the debris, and freeze-dried in the freeze dryer to be powdered.
상기 줄기는 가지와 가지에 붙어있는 잎사귀가 1 : 1 내지 2의 중량비로 혼합된 것이다. 가지를 기준으로 잎사귀의 함량이 상기 하한치 미만인 경우에는 꽃잎과 혼합시 미백효과를 발휘할 수 없으며, 상기 하한치 미만인 경우에는 독성을 유발할 수 있다. The stem is a mixture of branches and leaves attached to the branches in a weight ratio of 1: 1 to 2. When the content of the leaf is less than the lower limit based on the branch, the whitening effect can not be exhibited when mixed with the petal. If the content is less than the lower limit, toxicity may be caused.
본 발명의 월계화 추출물은 꽃잎 분말, 또는 꽃잎 분말과 줄기 분말이 혼합된 분말을 이용하여 추출물을 제조해야 우수한 미백효과를 발휘할 수 있다. 그러나 줄기 분말만을 이용하여 추출물을 제조하는 경우에는 미백효과를 전혀 기대할 수 없다.The extract of Walukae extract of the present invention can be excellently whitened by using an extract of petal powder or a mixture of petal powder and stem powder. However, the whitening effect can not be expected at all when the extract is prepared using only the stem powder.
상기 혼합 분말은 꽃잎 분말과 줄기 분말을 1 : 0.2 내지 0.9의 중량비, 바람직하게는 1 : 0.4 내지 0.6의 중량비로 혼합하여 추출한 것이다. 꽃잎을 기준으로 줄기의 함량이 상기 하한치 미만인 경우에는 우수한 미백효과를 기대할 수 없으며, 상기 상한치 초과인 경우에는 미백효과를 전혀 기대할 수 없다.The mixed powder is obtained by mixing the petal powder and the stem powder at a weight ratio of 1: 0.2 to 0.9, preferably 1: 0.4 to 0.6. When the content of stems on the basis of the petals is less than the lower limit value, an excellent whitening effect can not be expected, and when the content is above the upper limit value, whitening effect can not be expected at all.
다음으로, 상기 제조된 월계화 분말과 물을 1 : 8 내지 12, 바람직하게는 1 : 10 내지 12의 중량비로 혼합하여 80 내지 120 ℃, 바람직하게는 100 내지 120 ℃에서 0.5 내지 3시간, 바람직하게는 1.5 내지 2시간 동안 열수 추출한다.Next, the above-described launderability powder and water are mixed at a weight ratio of 1: 8 to 12, preferably 1:10 to 12, at 80 to 120 ° C, preferably 100 to 120 ° C for 0.5 to 3 hours, Is subjected to hot water extraction for 1.5 to 2 hours.
상기 추출용매로 물이 아닌 탄소수 1 내지 4의 저급알코올을 사용하는 경우에는 낮은 농도뿐만 아니라, 높은 농도로 처리 시에도 멜라닌 색소의 생성을 억제하지 못할 수 있다.When a lower alcohol having 1 to 4 carbon atoms other than water is used as the extraction solvent, the production of melanin pigment may not be suppressed even at a low concentration as well as at a high concentration.
추출 시 월계화 분말과 물의 함량이 상기 중량비를 벗어나는 경우에는 추출물에 월계화의 유효성분이 적은 양으로 추출될 수 있다.When the weight of the pomegranate powder and water is out of the above weight ratio, the effective amount of pomegranate may be extracted in a small amount.
또한, 추출온도가 상기 하한치 미만인 경우에는 멜라닌 색소의 생성을 전혀 억제하지 못할 수 있으며, 상기 상한치 초과인 경우에는 100 ug/ml 이하에서는 멜라닌 색소의 생성을 억제하지 못하고 100 ug/ml 이상의 고농도로 처리 시 알부민에 비하여 약 5% 감소된 미약한 멜라닌 색소의 생성 억제를 보일 수 있다.When the extraction temperature is lower than the lower limit, the production of melanin pigment may not be suppressed at all. If the extraction temperature is above the upper limit, the production of melanin pigment can not be inhibited at a concentration of 100 ug / ml or lower, It is possible to suppress the production of melanin pigment which is slightly reduced by about 5% as compared with cialumin.
또한, 추출시간이 상기 하한치 미만인 경우에는 월계화의 유효성분이 적은 양으로 추출될 수 있으며, 상기 상한치 초과인 경우에는 멜라닌 색소의 생성을 억제하지 못하고 독성을 유발할 수 있다.In addition, when the extraction time is less than the lower limit value, the effective amount of the laurel treatment can be extracted in a small amount. If the extraction time exceeds the upper limit value, the production of melanin pigment can not be inhibited and toxicity can be caused.
상기와 같이 제조된 월계화 추출물은 추출물 자체로 이용하거나 사용이 편리하도록 분말화하여 이용할 수 있다. 상기 월계화 추출물을 분말화하는 방법은 추출물을 감압 농축하여 부피를 줄인 후 동결건조기로 동결건조하여 분말화한다. The Walukehae extract prepared as described above may be used as an extract itself or may be pulverized for convenient use. In the method of pulverizing the mulberry flower extract, the extract is concentrated under reduced pressure to reduce its volume, and then lyophilized by a freeze dryer to be pulverized.
본 발명의 피부 미백 화장료 조성물에는 필수 성분인 상기 월계화 추출물과 더불어 필요에 따라 통상 화장료에 배합되는 다른 성분을 배합할 수 있으며, 이러한 배합 성분으로서는 유지 성분, 보습제, 에몰리엔트제, 계면 활성제, 유기 및 무기 안료, 유기 분체, 자외선 흡수제, 방부제, 살균제, 산화 방지제, pH 조정제, 알콜, 색소, 향료, 혈행 촉진제, 냉감제, 제한제, 정제수 등을 들 수 있다.The skin whitening cosmetic composition of the present invention may be blended with other components which are usually added to cosmetics, if necessary, in addition to the above-mentioned wattled calli extract, which is an essential ingredient. Examples of such blending ingredients include a moisturizing agent, an emollient agent, a surfactant, And an inorganic pigment, an organic powder, an ultraviolet absorber, an antiseptic, a bactericide, an antioxidant, a pH adjuster, an alcohol, a pigment, a flavor, a blood circulation promoter, a cold agent, a limiting agent and purified water.
상기 피부 미백 화장료 조성물은 당업계에서 통상 사용되는 유화 제형 및 가용화 제형의 형태로 제조될 수 있으며, 그 예로는 스킨 소프너, 스킨토너, 아스트린젠트, 로션, 밀크로션, 모이스처 로션, 영양로션, 마사지 크림, 영양크림, 모이스처 크림, 핸드크림, 에센스, 영양 에센스, 팩, 비누, 샴푸, 클렌징 폼, 클렌징 로션, 클렌징 크림, 바디로션, 바디클렌저, 유액, 프레스파우더, 루스파우더, 또는 아이섀도우 등을 들 수 있다.The skin whitening cosmetic composition may be prepared in the form of an emulsified formulation and a solubilized formulation commonly used in the art, and examples thereof include a skin softener, a skin toner, an astringent, a lotion, a milk lotion, a moisturizing lotion, Nutrition Creams, Moisture Creams, Hand Creams, Essences, Nutritional Essences, Packs, Soaps, Shampoos, Cleansing Foams, Cleansing Lotions, Cleansing Creams, Body Lotions, Body Cleansers, Milk, Press Powder, Loose Powder, or Eye Shadow have.
또한, 본 발명의 조성물은 월계화 추출물이 자체로 멜라닌 색소 대사 합성에 관여하는 효소들의 유전자 발현을 효과적으로 억제하여 우수한 피부 미백 활성을 갖는 바, 기미, 주근깨, 흑색점, 모반, 약물에 의한 색소 침착, 염증 후 색소 침착, 및 피부염에서 발생하는 과색소 침착 등의 피부 색소 침착 질환을 치료 또는 예방하는 용도의 약학적 조성물로도 사용될 수 있다.In addition, the composition of the present invention effectively inhibits gene expression of enzymes involved in melanin pigment metabolism synthesis, and thus has excellent skin whitening activity. Thus, the composition of the present invention has excellent skin whitening activity, As a pharmaceutical composition for treating or preventing skin pigmentation diseases such as hyperpigmentation, post-inflammatory pigmentation, and hyperpigmentation caused by dermatitis.
본 발명에서 상기 약학적 조성물에 포함된 월계화 추출물의 함량은 피부 색소 침착 질환의 종류, 증상의 경중, 사용 목적 등을 종합적으로 고려하여 조성물 총 중량 대비 0.001 내지 99.9 중량%의 함량으로 피부 색소 침착 질환의 치료 및 예방에 폭넓게 사용될 수 있다.In the present invention, the content of the rosemary extract contained in the pharmaceutical composition is preferably 0.001 to 99.9% by weight based on the total weight of the composition, taking into account the types of skin pigmentation diseases, the severity of symptoms, ≪ / RTI >
상기 약학적 조성물은 당업계에서 통상 피부에 도포하여 사용되는 어떠한 제형도 될 수 있으며, 그 예로는 크림, 젤, 패취, 분무제, 연고제, 경고제, 로션제, 리니멘트제, 파스타제, 또는 카타플라스마제 등을 들 수 있다.The pharmaceutical composition may be any of the formulations that are usually applied to the skin in the art and examples thereof include creams, gels, patches, sprays, ointments, alerts, lotions, liniments, pastes, And a plasma agent.
상기 월계화 추출물은 세포 독성을 보이지 않아 부작용에 대한 염려 없이 피부에 사용될 수 있으며, 상기와 같이 피부 외용 제제로 사용되어, 인체에 흡수되어 부작용을 나타낼 염려도 없고, 피부 표면에 어떠한 자극도 주지 않는다.As described above, it is used as an external preparation for skin to be absorbed into the human body, and there is no fear of side effects, and no irritation is given to the skin surface.
또한, 상기 약학적 조성물은 필요에 따라 약학적으로 허용 가능한 담체, 부형제, 희석제 또는 이들의 혼합물과 균질하게 혼합되어 사용될 수 있으며, 이러한 담체, 부형제, 또는 희석제의 예로는 바셀린, 유동 파라핀, 파라핀, 플라스티베이스(plastibase), 라드, 식물유, 왁스, 정제 라놀린 등과 같은 유지성 기제, 폴리에틸렌 글리콜 등과 같은 수용성 기제, 흡수 연고, 친수 연고와 같은 유제성 기제, 산화방지제, 방수제, 보습제, 연화보조제 등을 들 수 있다.In addition, the pharmaceutical composition may be used in a homogeneous mixture with a pharmaceutically acceptable carrier, excipient, diluent or a mixture thereof, if necessary. Examples of such carriers, excipients or diluents include petrolatum, liquid paraffin, paraffin, A water-soluble base such as plastibase, rod, vegetable oil, wax and refined lanolin, a water-soluble base such as polyethylene glycol, an emulsion base such as an ointment ointment, a hydrophilic ointment, an antioxidant, a waterproofing agent, a moisturizer and a softening aid have.
상기 약학적 조성물의 사용량은 피부 전체를 완전히 도포할 정도로 사용하면 되고, 특별히 양이 정해지는 것이 아니며, 사용 횟수 역시 사용하는 사용자의 편의에 따라서 수시로 피부에 도포하면 된다.
The amount of the pharmaceutical composition to be used is not particularly limited so long as it is sufficient to completely apply the entire skin, and the number of times of application may also be applied to the skin from time to time in accordance with the convenience of the user.
이하, 본 발명의 이해를 돕기 위하여 바람직한 실시예를 제시하나, 하기 실시예는 본 발명을 예시하는 것일 뿐 본 발명의 범주 및 기술사상 범위 내에서 다양한 변경 및 수정이 가능함은 당업자에게 있어서 명백한 것이며, 이러한 변형 및 수정이 첨부된 특허청구범위에 속하는 것도 당연한 것이다.It will be apparent to those skilled in the art that various modifications and variations can be made in the present invention without departing from the spirit or scope of the present invention. Such variations and modifications are intended to be within the scope of the appended claims.
실시예Example 1. 월계화 꽃잎 추출물 1. Rootten flower petal extract
월계화 꽃잎을 물로 세척한 후 물기를 제거한 다음 동결건조기로 분말화하였다. 상기 제조된 분말과 물을 1 : 10의 중량비로 혼합하여 100 ℃에서 2시간 동안 열수 추출하여 월계화 꽃잎 추출물을 수득하였다.
After drying the petals, they were pulverized with a freeze dryer. The powder thus prepared and water were mixed at a weight ratio of 1:10, and the mixture was subjected to hot water extraction at 100 ° C for 2 hours to obtain a rose flower petal extract.
실시예 2. 월계화 꽃잎 + 줄기 추출물Example 2. Rawalpinia flower + stem extract
상기 실시예 1과 동일하게 실시하되, 월계화 꽃잎과 줄기(가지:잎사귀=1:1 중량비)를 1 : 0.5의 중량비로 혼합한 분말 혼합물을 사용하여 월계화 추출물을 수득하였다.
The same procedure as in Example 1 was carried out except that a rosemary extract was obtained by using a powder mixture in which rosemary flower petals and stem (branch: leaf = 1: 1 weight ratio) were mixed at a weight ratio of 1: 0.5.
비교예 1. 월계화 줄기 추출물COMPARATIVE EXAMPLES 1. Ruminal stalk extract
상기 실시예 1과 동일하게 실시하되, 월계화 꽃잎 대신 월계화 가지와 잎사귀가 1 : 1의 중량비로 혼합한 줄기 분말을 사용하여 월계화 줄기 추출물을 수득하였다.
The same procedure as in Example 1 was carried out except that the stem powder mixed at a weight ratio of 1: 1 was used instead of the rosemary flower petal, and the rosemary stem extract was obtained.
비교예 2. 80% 에탄올Comparative Example 2 80% Ethanol
상기 실시예 1과 동일하게 실시하되, 추출용매로 물 대신 80% 에탄올을 사용하여 월계화 꽃잎 추출물을 수득하였다.
The same procedure as in Example 1 was carried out except that 80% ethanol was used instead of water as an extraction solvent to obtain a rose flower petal extract.
<시험예><Test Example>
시험예 1. 세포 독성 시험Test Example 1. Cytotoxicity test
실시예 및 비교예에서 제조된 월계화 추출물의 농도에 따른 세포독성을 측정하였다.Cytotoxicity was measured according to the concentrations of the extracts of Walukae extract prepared in Examples and Comparative Examples.
시료의 안전성 농도 범위에서 시험을 실행하기 위해 세포독성은 Rochem 등의 방법을 변형하여 측정하였다. 24 wells plate에 2 X 105 cells/well의 세포(RAW 264.7)를 분주한 후 24 시간동안 배양하였다. 이 후 배지를 제거하고 추출물이 용해된 serum이 3% 함유된 배지 1 mL을 분주하고 재배양을 24시간 동안 하였다. 24 시간 후 각 well에 0.25 mL의 XTT-PMS 용액(1 mg XTT and 10 g PMS/mL of MEM without phenol red)을 첨가하고 다시 2시간 배양하였다. 세포독성도는 formazan의 형성 정도를 microplate reader를 이용하여 450 nm에서 흡광도를 측정하여 안전성 농도 범위 확인 후 실험을 진행하였다. 상기 배지는 10%(v/v) fetal bovine serum(FBS), 0.5%(v/v) 50 g/mL streptomycin, 50 IU/mL penicillin, 0.125 g/mL fungizone, 3.024 g sodium bicarbonate를 함유한 MEM을 사용하였고, 배양은 37 ℃, 5% CO2, 95% humid air로 조절된 배양기를 사용하였다.Cytotoxicity was measured by the method of Rochem et al. In order to carry out the test in the safety concentration range of the sample. Cells (2 × 10 5 cells / well) (RAW 264.7) were seeded in 24-well plates and cultured for 24 hours. After that, the medium was removed and 1 mL of the medium containing 3% of the serum in which the extract was dissolved was dispensed and cultivation was carried out for 24 hours. After 24 hours, 0.25 mL of XTT-PMS solution (1 mg XTT and 10 g PMS / mL of MEM without phenol red) was added to each well and incubated for another 2 hours. The degree of cytotoxicity was determined by measuring the absorbance of formazan at 450 nm using a microplate reader. The medium was MEM supplemented with 10% (v / v) fetal bovine serum (FBS), 0.5% (v / v) 50 g / mL streptomycin, 50 IU / mL penicillin, 0.125 g / mL fungizone, 3.024 g sodium bicarbonate And incubated at 37 ℃, 5% CO 2, 95% humidified air.
위 표 1에 나타낸 바와 같이, 본 발명의 실시예 1 및 2에 따라 제조된 월계화 추출물은 10 내지 100 ug/ml 구간에서 독성이 나타나지 않는 것을 확인하였으며, 특히 실시예 2의 월계화 추출물의 세포 생존능이 가장 우수하였다.As shown in the above Table 1, it was confirmed that the rosiglitazone extract prepared according to Examples 1 and 2 of the present invention showed no toxicity in the interval of 10 to 100 ug / ml, and in particular, the cell viability of the rosiglitazone extract of Example 2 The best.
반면, 비교예 1 및 2는 10 내지 100 ug/ml의 전체 구간에서 독성이 나타나는 것을 확인하였다.
On the other hand, in Comparative Examples 1 and 2, it was confirmed that the toxicity appeared in the whole section of 10 to 100 ug / ml.
시험예Test Example 2. 멜라닌 생성 억제 효과 2. Melanin formation inhibitory effect
실시예 및 비교예에서 제조된 월계화 추출물이 멜라닌 색소의 생산을 감소시키는지 확인하기 위하여 흑색종 세포인 B16-F10 세포(ATCC, Manassas, USA)에 실시예 및 비교예에서 제조된 각 월계화 추출물과 대표적인 melanogenesis 유도제인 MSH(melanocyte stimulating hormone) 1 uM을 처리하여 3일 동안 배양하였다.In order to confirm whether or not the extract of Walukae extract prepared in Examples and Comparative Examples reduced the production of melanin pigment, B16-F10 cells (ATCC, Manassas, USA), melanoma cells, 1 μM melanocyte stimulating hormone (MSH), a representative inducer of melanogenesis, was treated and cultured for 3 days.
배양된 흑색종 세포의 멜라닌 색소 함량을 측정하기 위하여 생리식염수로 세척한 뒤 용출(lysis Buffer)로 용해시킨 뒤, 20% TCA용액으로 처리하였다. 침전물을 10% TCA 용액으로 2회 세척한 후, 다시 에탄올과 디에틸에테르의 혼합 용액(3:1), 및 디에틸에테르 용액으로 순차적으로 처리하고, 공기 중에서 건조시킨 후, 0.85 M의 수산화칼륨 용액으로 용해시켜 15 분간 가열하였다. 냉각 후 440 nm에서 흡광도를 측정하였다. 세포 수에 따른 멜라닌 색소 함량 차이를 보정하기 위해, 브래드포드 방법(Bradford Method, Anal Biochem 1976;72:248-54)으로 단백질을 정량하고, 멜라닌 색소의 측정량을 단백질량으로 나누어 1 mg 단위 단백질당 멜라닌 색소 생성량 측정치(멜라닌 색소 측정량/단백질)를 하기 [표 2]에 나타내었다. 대조군으로는 α-MSH을 사용하지 않고 월계화 추출물로만 처리된 흑색종 세포이다.The melanin content of cultured melanoma cells was measured by washing with physiological saline, dissolution with lysis buffer, and treatment with 20% TCA solution. The precipitate was washed twice with 10% TCA solution, and then sequentially treated with a mixed solution of ethanol and diethyl ether (3: 1) and diethyl ether solution, and dried in air. Then, 0.85 M potassium hydroxide Solution and heated for 15 minutes. After cooling, the absorbance was measured at 440 nm. Proteins were quantified by the Bradford method (Anal Biochem 1976; 72: 248-54) and the measured amount of melanin pigment was divided by the amount of protein to obtain 1 mg unit protein The measured amount of melanin pigment production (melanin pigment measurement amount / protein) is shown in Table 2 below. As a control, melanoma cells were treated with ugly extract only without α-MSH.
위 표 2에 나타낸 바와 같이, 본 발명의 실시예 1 및 2에 따라 제조된 월계화 추출물은 10 ug/ml 이상부터 대표적인 멜라닌 생성 억제제인 알부민보다 더욱 우수한 멜라닌 생성 억제 효과를 나타내는 것으로 확인하였다. 특히, 실시예 2의 월계화 추출물이 가장 우수한 멜라닌 생성 억제 효과를 나타내었다.As shown in Table 2 above, it was confirmed that the extracts of Walukae extract prepared according to Examples 1 and 2 of the present invention exhibit a more excellent melanin production inhibitory effect than albumin, which is a typical melanin formation inhibitor, from 10 ug / ml or more. In particular, the writhing extract of Example 2 showed the most excellent melanin production inhibitory effect.
반면, 비교예 1 및 2는 10 내지 100 ug/ml의 전체 구간에서 멜라닌 생성 억제 효과가 거의 나타나지 않은 것을 확인하였다.
On the other hand, in Comparative Examples 1 and 2, it was confirmed that the melanin formation inhibitory effect was hardly exhibited in the entire section of 10 to 100 ug / ml.
시험예Test Example 3. 3. 타이로시나아제Tyrosinase 활성 억제 효과 Activity inhibitory effect
멜라닌 색소의 형성에 중요한 역할을 하는 타이로시나아제의 활성에 월계화 추출물이 미치는 영향을 평가하였다.The effects of ugly extracts on the activity of tyrosinase, which plays an important role in the formation of melanin pigment, were evaluated.
시험예 2의 α-MSH 및 월계화 추출물이 처리된 흑색종 세포의 세포 용출물을 이용하여 도파(DOPA)가 도파 크롬(DOPA chrome)으로 산화되는 반응을 475 nm에서 분광광도계(spectrophotometer)로 측정하였다. 상기 반응은 신선하게 조제한 기질용액(0.1 % L-DOPA in 0.1 M sodium phosphate, pH 6.0)에 세포 용출물을 가한 후 37 ℃에서 부치시키면서 측정하였다. 그리고 타이로시나아제 활성은 상기 시험예 2에서 기술된 단백질 정량 방법을 사용하여 1 mg 단위 단백질당 타이로시나아제 활성으로 보정하여 하기 [표 3]에 나타내었다. 대조군으로는 α-MSH을 사용하지 않고 월계화 추출물로만 처리된 흑색종 세포이다.(DOPA) was oxidized to DOPA chrome by using a cell eluate of melanoma cells treated with α-MSH and urea extract of Test Example 2 by a spectrophotometer at 475 nm . The reaction was carried out by adding the cell extract to a freshly prepared substrate solution (0.1% L-DOPA in 0.1 M sodium phosphate, pH 6.0) and incubating at 37 ° C. And tyrosinase activity was corrected by tyrosinase activity per 1 mg unit protein using the protein quantification method described in Test Example 2, and is shown in Table 3 below. As a control, melanoma cells were treated with ugly extract only without α-MSH.
세포내 멜라닌 생성 억제 효과는 melanogenesis의 중추적인 효소인 타이로시나이제의 활성을 저해함으로써 나타난다.The inhibitory effect of intracellular melanin production is shown by inhibiting the activity of tyrosinase, a key enzyme of melanogenesis.
위 표 3에 나타낸 바와 같이, 본 발명의 실시예 1 및 2에 따라 제조된 월계화 추출물은 10 ug/ml 이상부터 알부민보다 더욱 우수한 타이로시나이제 활성 저해를 나타내는 것으로 확인되었다. As shown in Table 3 above, it was confirmed that the extracts of Walukae extract prepared according to Examples 1 and 2 of the present invention exhibited more excellent inhibition of tyrosinase activity than albumin over 10 ug / ml.
반면, 비교예 1 및 2는 10 내지 100 ug/ml의 전체 구간에서 알부민보다 우수하지 않게 타이로시나이제 활성을 저해하는 것을 확인하였다.
On the other hand, it was confirmed that Comparative Examples 1 and 2 inhibited tyrosinase activity not better than albumin in the whole section of 10 to 100 ug / ml.
시험예Test Example 4. 피부 미백 효과 4. Skin whitening effect
사람의 상완부 안쪽 피부에 각각 세 곳씩, 2 X 2 cm2 면적에 400 mJ/cm2의 자외선(UVB)을 1주일에 5회, 1주간 조사하여(Aurora UV-Light, 조양메딕스, 성남) 색소 침착을 유도하였다.(Aurora UV-Light, Chaiyang Medix, Seongnam) by irradiating ultraviolet rays (UVB) of 400 mJ / cm 2 onto the inside of the upper arm of a human, three times each at 2 x 2 cm 2 area for 5 weeks, Deposition was induced.
상기 색소 침착이 유도된 사람 피부에 월계화 추출물 원액을 자외선 조사 시작 2주 후부터 10주까지 매일 2회 지속적으로 도포하여 월계화 추출물이 피부 미백에 미치는 효과를 평가하였다. 대조군으로는 반대쪽 상완에 동일한 조건에서 자외선을 조사한 후, 아무런 처리를 하지 않은 군을 사용하였다.The effect of the rosemary extract extract on skin whitening effect was evaluated by continuously applying the crude extract of rosemary extract to the skin of the above-mentioned pigmentation-induced human skin twice a day for 2 weeks to 10 weeks from the beginning of UV irradiation. As a control group, the other arm was irradiated with ultraviolet light under the same conditions, and the group without any treatment was used.
피부 미백 효과는 멕사메터(CK, Mexameter, MPA 9, Courage, Khazaka, Germany)를 이용하여 MI(melanogenic index) 값을 측정하였고, 월계화 추출물을 도포하기 시작한 시점에서의 MI 값과의 차이(△MI)를 [표 4]에 나타내었다.The skin whitening effect was measured by measuring the MI (melanogenic index) value using a mexameter (CK, Mexameter, MPA 9, Courage, Khazaka, Germany), and the difference ) Are shown in [Table 4].
위 표 4에 나타낸 바와 같이, 본 발명의 실시예 1 및 2에 따라 제조된 월계화 추출물은 추출물을 처리하자마자 △MI 값이 감소하기 시작하였고, 8주 경과시까지 꾸준하게 △MI 값이 감소하여, 추출물을 처리한 지 8주째에는 △MI 값이 -26 내지 -33까지 감소(linearly decline) 되므로 멜라닌 색소 형성이 유도된 피부에 작용하여 우수한 피부 미백 효과를 가짐을 알 수 있다.As shown in the above Table 4, the ura value of MIW started to decrease as soon as the extract was treated and the Δ MI value decreased steadily until 8 weeks, , The ΔMI value is linearly declined to -26 to -33, so that it acts on the skin induced by melanin pigment formation and has an excellent skin whitening effect.
반면, 비교예 1 및 2는 아무처리하지 않은 대조군과 유사한 수치를 보이는 것으로 보아 미백에 아무런 효과가 없는 것으로 확인되었다. 상기 대조군과 비교예 1 및 2는 자외선 조사 후 4주 경과 시까지 멜라닌 생성이 증가하였고, 8주 경과 시에도 뚜렷한 멜라닌 생성 감소 추세가 관찰되지 않았다.
On the other hand, Comparative Examples 1 and 2 were found to have no effect on whitening by showing similar values to those of the untreated control group. Melanogenesis was increased in the control group and Comparative Examples 1 and 2 by 4 weeks after irradiation with ultraviolet light, and no significant decrease of melanin production was observed even after 8 weeks.
하기에 본 발명의 추출물을 함유하는 조성물의 제제예를 설명하나, 본 발명은 이를 한정하고자 함이 아닌 단지 구체적으로 설명하고자 함이다.Hereinafter, formulation examples of the composition containing the extract of the present invention will be described, but the present invention is not intended to be limited thereto but is specifically described.
제제예Formulation example 1. 유화 제형의 화장품의 제조 1. Manufacture of cosmetic products of emulsified formulations
영양화장수, 크림, 에센스 등의 유화 제형의 화장품 및 유연화장수 등의 가용화 제형의 화장품을 제조하였다.Cosmetics of emulsified form such as nutrient lotion, cream, essence, and cosmetics of solubilized form such as softened longevity were prepared.
하기 표 5에 기재된 조성으로 유화제형의 화장품을 제조하였다. 제조방법은 하기와 같다.Emulsifier type cosmetics were prepared with the compositions shown in Table 5 below. The production method is as follows.
1) 1 내지 9의 원료를 혼합한 혼합물을 65 내지 70 ℃로 가열하였다.1) A mixture of raw materials 1 to 9 was heated to 65 to 70 占 폚.
2) 10의 원료를 상기 단계 1)의 혼합물에 투입하였다.2) The starting material of 10 was added to the mixture of step 1).
3) 11 내지 13의 원료의 혼합물을 65 내지 70 ℃로 가열하여 완전히 용해시켰다.3) The mixture of raw materials 11 to 13 was completely dissolved by heating to 65 to 70 占 폚.
4) 상기 단계 3)을 거치면서, 상기 2)의 혼합물을 서서히 첨가하여 8,000 rpm에서 2 내지 3분간 유화시켰다.4) While the above step 3) was carried out, the mixture of step 2) was gradually added and emulsified at 8,000 rpm for 2 to 3 minutes.
5) 14의 원료를 소량의 물에 용해시킨 후 상기 단계 4)의 혼합물에 첨가하고 2분간 더 유화시켰다.5) The raw material of 14 was dissolved in a small amount of water and then added to the mixture of step 4) and further emulsified for 2 minutes.
6) 15 내지 17의 원료를 각각 평량한 후 상기 단계 5)의 혼합물에 넣고 30초간 더 유화시켰다.6) The raw materials of 15 to 17 were each weighed, and then put into the mixture of step 5) and further emulsified for 30 seconds.
7) 상기 단계 6)의 혼합물을 유화 후 탈기과정을 거쳐 25 내지 35 ℃로 냉각시킴으로써 유화제형의 화장품을 제조하였다.7) The mixture of step 6) was degassed after emulsification and cooled to 25-35 占 폚 to prepare an emulsifier-type cosmetic.
모노라우린산 에스테르Polyoxyethylene sorbitan
Monolauric acid ester
제제예Formulation example 2. 2. 가용화Solubilization 제형의 화장품의 제조 Manufacture of Cosmetics for Formulation
하기 표 6에 기재된 조성으로 가용화제형의 화장품을 제조하였다. 제조방법은 하기와 같다.Cosmetics of the solubilized formulations were prepared with the compositions shown in Table 6 below. The production method is as follows.
1) 2 내지 6의 원료를 1의 원료(정제수)에 넣고 아직믹서를 이용하여 용해시켰다.1) 2 to 6 raw materials were put into 1 raw material (purified water) and dissolved using a mixer.
2) 8 내지 11의 원료를 7의 원료(알코올)에 넣고 완전용해시켰다.2) Raw materials 8 to 11 were completely dissolved in 7 raw materials (alcohol).
3) 상기 단계 2)의 혼합물을 상기 단계 1)의 혼합물에 서서히 첨가하면서 가용화시켰다.3) The mixture of step 2) was slowly solubilized by adding it to the mixture of step 1).
하이드로제네이디트에스테르Polyoxyethylene
Hydro genide ester
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월계화 추출물의 멜라닌 합성기전에 대한 효능 연구, 대전대학교, 석사학위논문(2009, 12).* |
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