TW202007407A - Angelica dahurica ferment, preparation method thereof and use thereof for improving skin appearance - Google Patents
Angelica dahurica ferment, preparation method thereof and use thereof for improving skin appearance Download PDFInfo
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- TW202007407A TW202007407A TW108111036A TW108111036A TW202007407A TW 202007407 A TW202007407 A TW 202007407A TW 108111036 A TW108111036 A TW 108111036A TW 108111036 A TW108111036 A TW 108111036A TW 202007407 A TW202007407 A TW 202007407A
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- angelica
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Images
Classifications
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/23—Apiaceae or Umbelliferae (Carrot family), e.g. dill, chervil, coriander or cumin
- A61K36/232—Angelica
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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
- A23L33/105—Plant extracts, their artificial duplicates or their derivatives
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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
- A61K8/9783—Angiosperms [Magnoliophyta]
- A61K8/9789—Magnoliopsida [dicotyledons]
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- 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
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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
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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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- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
- A23V2002/00—Food compositions, function of food ingredients or processes for food or foodstuffs
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2236/00—Isolation or extraction methods of medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicine
- A61K2236/10—Preparation or pretreatment of starting material
- A61K2236/19—Preparation or pretreatment of starting material involving fermentation using yeast, bacteria or both; enzymatic treatment
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2800/00—Properties of cosmetic compositions or active ingredients thereof or formulation aids used therein and process related aspects
- A61K2800/80—Process related aspects concerning the preparation of the cosmetic composition or the storage or application thereof
- A61K2800/85—Products or compounds obtained by fermentation, e.g. yoghurt, beer, wine
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2800/00—Properties of cosmetic compositions or active ingredients thereof or formulation aids used therein and process related aspects
- A61K2800/80—Process related aspects concerning the preparation of the cosmetic composition or the storage or application thereof
- A61K2800/92—Oral administration
Abstract
Description
本發明係關於一種白芷發酵物及其製備方法與用於製備改善皮膚外觀之組合物的用途，尤其是一種白芷發酵物用於提升皮膚保水度、提升皮膚亮澤度、及/或淡化皮膚色斑之用途；其中，該白芷發酵物係將由一白芷萃取物所組成之混合物以酵母菌、胚芽乳桿菌、及醋酸桿菌依序進行三段式發酵而獲得。 The present invention relates to a fermented Angelica dahurica and its preparation method and use for preparing a composition for improving the appearance of skin, in particular a fermented Angelica dahurica used to improve the skin's water retention, enhance skin's luster, and/or lighten skin color The use of plaque; wherein, the Angelica dahurica fermented material is obtained by performing a three-stage fermentation of yeast, Lactobacillus and Acetobacter in a mixture composed of an Angelica extract.
表皮層為皮膚的最外層，由外往內依序為角質層、顆粒層、有棘層及基底層，表皮層主要由基底層中未分化之圓柱型角質細胞持續向上進行分化形成，此過程稱為角質化。角質細胞內含水量高，隨著細胞向上代謝分化，角質細胞形狀會逐漸變成扁平狀，且細胞核及胞器開始退化萎縮，並在角質層形成不具細胞核與胞器之死細胞。表皮層的主要功能為使皮膚保水，並形成皮膚屏障以抵禦各種外來傷害，其中表皮層最外層由一弱酸性的皮脂膜以及如磚牆結構的角質層所構成，此屏障能鎖住皮膚的水分和油脂、抵抗皮膚表面病菌入侵，及對抗外界異物及紫外光等傷害，對人體有非常重要的保護作用。 The epidermal layer is the outermost layer of the skin, which is the stratum corneum, the granular layer, the spinous layer and the basal layer in sequence from the outer to the inner. The epidermal layer is mainly formed by the continuous differentiation of the undifferentiated cylindrical keratinocytes in the basal layer. This process Called keratinization. Keratinocytes have a high water content. As the cells metabolize and differentiate, the shape of the keratinocytes will gradually become flat, and the nuclei and organelles will begin to degenerate and shrink, and dead cells without nucleus and organelles will form in the stratum corneum. The main function of the epidermal layer is to keep the skin water-retaining and form a skin barrier to resist various external damages. The outermost layer of the epidermal layer is composed of a weakly acidic sebum film and the stratum corneum like a brick wall structure. This barrier can lock the skin. Moisture and oil, resist the invasion of bacteria on the skin surface, and resist the damage of foreign bodies and ultraviolet light, etc., have a very important protective effect on the human body.
表皮層中的角質層，其角質細胞雖然為死細胞，但其主要成分為角蛋白(keratin)，角蛋白能吸收水分使皮膚保持濕潤，角質細胞也會分泌如玻尿酸等物質作為細胞間質，以維持表皮層皮膚屏障之結構完整，以防止皮膚水 分散失及形成完整防護。當皮膚接觸過冷或過熱之環境以及照射紫外光等刺激，會導致角質細胞無法維持正常的代謝循環，且皮膚保水能力也會下降，並導致皮膚表皮層屏障受損，讓皮膚變得粗糙、乾燥脫屑、脆弱易受刺激、敏感泛紅，因此角質層的健康與保水能力對於抵禦外來傷害著實非常重要。 In the stratum corneum of the epidermal layer, although the keratinocytes are dead cells, the main component is keratin. Keratin can absorb water to keep the skin moist. Keratinocytes also secrete substances such as hyaluronic acid as the intercellular substance. In order to maintain the integrity of the structure of the skin barrier of the epidermal layer, to prevent the skin from losing water and forming a complete protection. When the skin is exposed to excessively cold or overheated environments and irradiated with ultraviolet light and other stimuli, the keratinocytes cannot maintain the normal metabolic cycle, and the skin's ability to retain water is also reduced, resulting in damage to the skin's epidermal barrier, making the skin rough, Dry and desquamated, fragile and susceptible to irritation, sensitive redness, so the health of the stratum corneum and the ability to retain water are very important to resist external damage.
另外，近年來為達到人們努力追求皮膚白皙及斑點漸少的需求，市面上不斷開發出各種抑制黑色素形成或淡化斑點之美白產品，然而，該些產品為訴求達到特殊效果，而加入過多致癌的化學物質或環境荷爾蒙，使消費者在不知情的狀況下使用會傷害皮膚影響健康的成分。 In addition, in recent years, in order to meet people's demand for fair skin and less spots, various whitening products have been developed on the market to suppress melanin formation or lighten spots. However, these products have added too much carcinogen in order to achieve special effects. Chemical substances or environmental hormones cause consumers to use ingredients that can harm skin and affect health without knowing it.
綜合上面所述，為了改善因角質細胞受損、保水能力下降、以及皮膚老化所導致皮膚變得脆弱、易敏等問題，且因應講求天然健康的現代，開發一種能有效使提升皮膚保水能力，以維持角質細胞排列、維持角質層結構完整，且又能兼顧皮膚美白訴求之皮膚綜合保健組合物，著實有其必要性。 Based on the above, in order to improve the problems of keratinocyte damage, decreased water retention capacity, and skin aging caused by skin aging and fragility, and sensitivity, and in response to the need for natural and healthy modern, develop a method that can effectively improve skin water retention capacity, In order to maintain the arrangement of keratinocytes, maintain the integrity of the stratum corneum structure, and can also take into account the skin whitening appeal, it is indeed necessary.
緣此，本發明之一目的在提供一種白芷發酵物，其中該白芷發酵物係由一白芷經由一溶劑萃取所得之白芷萃取物，再經由一酵母菌(Saccharomyces cerevisiae)、一胚芽乳桿菌(Lactobacillus plantarum)、及一醋酸桿菌(Acetobacter aceti)依序進行發酵而獲得。 Therefore, one object of the present invention is to provide an Angelica flavescens fermented product, wherein the Angelica flavescens fermented product is an Angelica dahurica extract obtained by extracting an Angelica dahurica through a solvent, and then through a yeast ( Saccharomyces cerevisiae ) and a Lactobacillus plantarum ) and Acetobacter aceti are obtained by fermentation in sequence.
本發明之又一目的在提供一種如前所述之白芷發酵物用於製備一提升皮膚保水度之組合物的用途；且該白芷發酵物之有效濃度為至少5%(v/v)。 A further object of the present invention is to provide a use of the fermented Angelica dahurica as described above for preparing a composition for improving skin water retention; and the effective concentration of the fermented Angelica dahuricae is at least 5% (v/v).
本發明之又一目的在提供一種如前所述之白芷發酵物用於製備一提升皮膚亮澤度之組合物的用途；且該白芷發酵物之有效濃度為至少5%(v/v)。 Another object of the present invention is to provide the use of the Angelicae dahurica fermented material as described above for the preparation of a skin brightness enhancing composition; and the effective concentration of the Angelica dahuricae fermented product is at least 5% (v/v).
本發明之又一目的在提供一種如前所述之白芷發酵物用於製備一淡化皮膚色斑之組合物的用途；且該白芷發酵物之有效濃度為至少5%(v/v)。 Another object of the present invention is to provide a use of the fermented Angelica dahurica as described above for preparing a composition for lightening skin stains; and the effective concentration of the fermented Angelica dahuricae is at least 5% (v/v).
本發明之另一目的在提供一種白芷發酵物之製造方法，係包含：將一白芷經由一溶劑萃取所得之白芷萃取物，該白芷萃取物再經由一酵母菌(Saccharomyces cerevisiae)、一胚芽乳桿菌(Lactobacillus plantarum)、及一醋酸桿菌(Acetobacter aceti)依序進行三階段發酵而獲得。 Another object of the present invention is to provide a method for manufacturing fermented Angelica dahuricae, which comprises: an extract of Angelica dahurica obtained by extracting an Angelica dahurica through a solvent, the Angelica dahurica extract through a yeast ( Saccharomyces cerevisiae ), a Lactobacillus germ ( Lactobacillus plantarum ) and Acetobacter aceti are obtained by three-stage fermentation in sequence.
在本發明之一實施例中，該白芷萃取物係以水為溶劑在50-100℃下萃取該白芷0.5-3小時所獲得；該白芷及水係以1：1-10(w/w)之比例混合；該酵母菌之添加量為0.01-0.5%(w/w)；該胚芽乳桿菌之添加量為0.01-0.25%(w/w)；該醋酸桿菌之添加量為1-20%(w/w)；且該酵母菌、該胚芽乳桿菌、及該醋酸桿菌之發酵時間比為1-2：1-3：5-10。 In one embodiment of the present invention, the Radix Angelicae dahuricae extract is obtained by extracting the Radix Angelicae dahuricae with water as the solvent at 50-100°C for 0.5-3 hours; the Radix Angelicae dahuricae and the water system are 1:1-10 (w/w) Mix the ratio; the addition amount of the yeast is 0.01-0.5% (w/w); the addition amount of the Lactobacillus germ is 0.01-0.25% (w/w); the addition amount of the Acetobacter is 1-20% (w/w); and the fermentation time ratio of the yeast, the Lactobacillus germ, and the Acetobacter is 1-2:1-3:5-10.
在本發明之又一實施例中，該白芷發酵物具有減少皮膚表皮色斑使皮膚淨透白皙之功效。 In yet another embodiment of the present invention, the fermented Angelica dahuricae has the effect of reducing skin epidermal spots and making the skin clear and fair.
在本發明之又一實施例中，該白芷發酵物具有改善皮膚暗沉、枯黃的情況使皮膚透亮有光澤之功效。 In yet another embodiment of the present invention, the fermented Angelicae dahurica has the effect of improving the dull and yellow skin and making the skin translucent and shiny.
在本發明之另一實施例中，該白芷發酵物具有改善皮膚乾燥、缺水的情況使皮膚水潤有彈性之功效。 In another embodiment of the present invention, the fermented Angelica dahurica has the effect of improving the dryness and dehydration of the skin and making the skin moist and elastic.
本發明將白芷萃取物以酵母菌、胚芽乳桿菌、及醋酸桿菌進行三段式發酵所得之白芷發酵物，能藉由該微生物發酵製程使白芷的效性物質多醣大量釋出；本發明之白芷發酵物能有效淡化個體皮膚之紫外線色斑，以減少皮膚表皮色斑使皮膚淨透白皙；能有效提升個體皮膚之亮澤度，以改善皮膚暗沉、枯黃的情況使皮膚透亮有光澤；能有效提升個體皮膚之保水度，以改善皮膚乾燥、缺水的情況使皮膚水潤有彈性。因此，本發明之白芷發酵物可用於製備改善皮膚外觀之組合物的用途，且該組合物是一醫藥品、一保養品、或一食品，可藉由口服、塗抹等方式給予一個體。 In the invention, the Angelica dahurica extract obtained by three-stage fermentation of yeast, Lactobacillus germ, and Acetobacter can be used to release a large amount of the active substance polysaccharide of Angelica dahurica through the microorganism fermentation process; The fermented product can effectively lighten the ultraviolet spots of the individual skin to reduce the skin epidermal spots and make the skin clear and white; it can effectively improve the brightness of the individual skin to improve the dull and yellow skin and make the skin translucent and shiny; Effectively improve the moisture retention of individual skin, to improve dry skin and lack of water, make skin moist and elastic. Therefore, the fermented Angelica dahurica of the present invention can be used to prepare a composition for improving the appearance of skin, and the composition is a medicine, a care product, or a food, and can be administered to a body by oral administration, smearing, or the like.
以下將配合圖式進一步說明本發明的實施方式，下述所列舉的實施例係用以闡明本發明，並非用以限定本發明之範圍，任何熟習此技藝者，在不脫離本發明之精神和範圍內，當可做些許更動與潤飾，因此本發明之保護範圍當視後附之申請專利範圍所界定者為準。 The embodiments of the present invention will be further described below with reference to the drawings. The examples listed below are used to clarify the present invention and are not intended to limit the scope of the present invention. Anyone who is familiar with this art without departing from the spirit and spirit of the present invention Within the scope, some changes and retouching can be done, so the protection scope of the present invention shall be subject to the scope defined in the appended patent application.
圖1係為本發明之一實施例的白芷發酵物淡化個體皮膚紫外線色斑的長條圖。 FIG. 1 is a bar graph of the Angelica fermented material to lighten the ultraviolet spots of individual skin according to an embodiment of the present invention.
圖2係為本發明之一實施例的白芷發酵物提升個體皮膚亮澤度的長條圖。 FIG. 2 is a bar graph of the Angelica fermented material improving the brightness of an individual’s skin according to an embodiment of the present invention.
圖3係為本發明之一實施例的白芷發酵物提升個體皮膚保水度的長條圖。**p<0.01。 FIG. 3 is a bar graph of the Angelica fermented material improving water retention of an individual’s skin according to an embodiment of the present invention. **p<0.01.
本文中所使用數值為近似值，所有實驗數據皆表示在20%的範圍內，較佳為在10%的範圍內，最佳為在5%的範圍內。 The numerical values used in this article are approximate values, and all experimental data are expressed within a range of 20%, preferably within a range of 10%, and most preferably within a range of 5%.
使用Excel軟體進行統計分析。數據以平均值±標準差(SD)表示，個此之間的差異以學生t檢驗(student's t-test)分析。 Use Excel software for statistical analysis. Data mean ± standard deviation (SD) represented by the difference between the two herein by Student t test (student's t -test) analysis.
白芷(Angelica dahurica)為繖(傘)形科(Apiaceae)當歸屬(Angelica)多年生草本植物，又稱紫花前胡、野當歸、山芹菜、獨活、鴨腳前胡、鴨腳當歸、老虎爪等名。白芷植株高約1-2.5公尺，根呈圓柱形，顏色為棕黃色至棕褐色，具有強烈氣味；莖基部直徑約2-5公分；葉呈羽狀分裂；花序呈複繖形，且為頂生或側生；果實則呈長圓形或卵圓形。白芷的根常作為中藥，具有活血止痛、祛病除溼、治療感冒之功效。 Angelica dahurica ( Angelica dahurica ) is an umbrella ( Umbelliferae ) Apiaceae ( Angelica ) Angelica ( Angica ) perennial herb, also known as Ligustrum lucidum, wild angelica, celery, solitary live, duck feet before Hu, duck feet angelica, tiger claw Equal name. Angelica plant is about 1-2.5 meters tall, the root is cylindrical, the color is brownish yellow to brown, and has a strong smell; the base of the stem is about 2-5 cm in diameter; the leaves are split like feathers; the inflorescence is compound umbrella-shaped, and is terminal Or lateral; the fruit is oblong or oval. Angelica root is often used as a traditional Chinese medicine, which has the effects of activating blood circulation to relieve pain, remove diseases and dampness, and treat colds.
如本文中所使用的，用語「白芷發酵物」意為白芷與溶劑以1：1-10(w/w)比例經一特定時間與溫度萃取而得之白芷萃取物，再以酵母菌、胚芽乳桿 菌、及醋酸桿菌依序進行一三段式發酵而獲得，其中該酵母菌之添加量為0.01-0.5%(w/w)；該胚芽乳桿菌之添加量為0.01-0.25%(w/w)；該醋酸桿菌之添加量為1-20%(w/w)。 As used herein, the term "fermented Angelica dahurica" means the extract of Angelica dahurica extracted from Angelica dahurica and solvent at a ratio of 1:1-10 (w/w) at a specific time and temperature, and then yeast, germ Lactobacillus and Acetobacter are obtained in a three-stage fermentation in sequence, in which the addition amount of the yeast is 0.01-0.5% (w/w); the addition amount of the Lactobacillus germ is 0.01-0.25% (w/ w); The added amount of Acetobacter is 1-20% (w/w).
本文所述之「有效濃度」係表示能有效淡化個體皮膚色斑、有效提升個體皮膚亮澤度、及/或有效提升個體皮膚保水度所需本發明之白芷發酵物的濃度。有效濃度依所作用的對象而可能不同，但可藉由例如劑量遞增試驗(dose escalation)以實驗決定其有效濃度。 "Effective concentration" as used herein refers to the concentration of the Angelica dahurica fermented substance required to effectively lighten the skin spots of an individual, effectively enhance the brightness of the individual's skin, and/or effectively enhance the water retention of the individual's skin. The effective concentration may be different depending on the target, but the effective concentration can be determined experimentally by, for example, dose escalation.
依據本發明，有關微生物發酵反應的操作程序與參數條件等是落在熟習此項技術之人士的專業素養與例行技術範疇內。 According to the present invention, the operating procedures and parameter conditions related to microbial fermentation reactions fall within the scope of professional literacy and routine technology of those skilled in the art.
依據本發明，醫藥品可利用熟習此技藝者所詳知的技術而被製造成一適合於非經腸道地(parenterally)或局部地(topically)投藥的劑型，這包括，但不限於：注射品(injection)[例如，無菌的水性溶液(sterile aqueous solution)或分散液(dispersion)]、無菌的粉末(sterile powder)、外部製劑(external preparation)以及類似之物。 According to the present invention, pharmaceutical products can be manufactured into a dosage form suitable for parenterally or topically administration using techniques well known to those skilled in the art, including, but not limited to: injections (injection) [for example, sterile aqueous solution or dispersion], sterile powder, external preparation, and the like.
依據本發明，醫藥品可進一步包含有一被廣泛地使用於藥物製造技術之醫藥上可接受的載劑(pharmaceutically acceptable carrier)。例如，該醫藥上可接受的載劑可包含一或多種選自但不限於下列的試劑：溶劑(solvent)、緩衝液(buffer)、乳化劑(emulsifier)、懸浮劑(suspending agent)、分散劑(dispersing agent)、賦形劑(excipient)、安定劑(stabilizing agent)、螯合劑(chelating agent)、稀釋劑(diluent)、防腐劑(preservative)、吸收延遲劑(absorption delaying agent)、脂質體(liposome)以及類似之物。有關這些試劑的選用與數量是落在熟習此項技術之人士的專業素養與例行技術範疇內。 According to the present invention, the pharmaceutical product may further include a pharmaceutically acceptable carrier widely used in pharmaceutical manufacturing technology. For example, the pharmaceutically acceptable carrier may include one or more agents selected from but not limited to the following: solvent, buffer, emulsifier, suspending agent, dispersing agent (dispersing agent), excipient, stabilizing agent, chelating agent, diluent, preservative, absorption delaying agent, liposome ( liposome) and the like. The selection and quantity of these reagents fall within the professional qualities and routine techniques of those who are familiar with this technology.
依據本發明，該醫藥上可接受的載劑包含有一選自於由下列所構成之群組中的溶劑：水、生理鹽水(normal saline)、磷酸鹽緩衝生理鹽水 (phosphate buffered saline,PBS)、含有醇的水性溶液(aqueous solution containing alcohol)以及它們的組合。 According to the present invention, the pharmaceutically acceptable carrier contains a solvent selected from the group consisting of water, normal saline, phosphate buffered saline (PBS), Aqueous solution containing alcohol and their combination.
依據本發明，該醫藥品可以一選自於由下列所構成之群組中的非經腸道途徑(parenteral routes)來投藥：皮下注射(subcutaneous injection)、表皮內注射(intraepidermal injection)、皮內注射(intradermal injection)以及病灶內注射(intralesional injection)。 According to the present invention, the medicinal product can be administered via parenteral routes selected from the group consisting of subcutaneous injection, intraepidermal injection, and intradermal injection Intradermal injection and intralesional injection.
依據本發明，醫藥品可利用熟習此技藝者所詳知的技術而被製造成一適合於局部地施用於皮膚上的外部製劑(external preparation)，這包括，但不限於：乳劑(emulsion)、凝膠(gel)、軟膏(ointment)、乳霜(cream)、擦劑(liniment)、粉末(powder)、噴霧(spray)、乳液(lotion)、以及油膏(salve)。 According to the present invention, pharmaceutical products can be manufactured into an external preparation suitable for topical application to the skin using techniques well known to those skilled in the art, which include, but are not limited to: emulsion, gel Gels, ointments, creams, liniments, powders, sprays, lotions, and salves.
依據本發明，該外部製劑是藉由將本發明的醫藥品與一為熟習此項技藝者所詳知的基底(base)相混合而被製備。 According to the present invention, the external preparation is prepared by mixing the pharmaceutical product of the present invention with a base well known to those skilled in the art.
依據本發明，該基底可包含有一或多種選自但不限於下列的添加劑(additives)：水、醇(alcohols)、甘醇(glycol)、保存劑(preserving agents)、抗氧化劑(antioxidants)、界面活性劑(surfactants)、吸收增強劑(absorption enhancers)、安定劑(stabilizing agents)、pH調整劑(pH adjusting agents)、螯合劑(chelating agents)、乳化劑(emulsifiers)、增稠劑(thickeners)、助溶劑(solubilizing agents)、滲透增強劑(penetration enhancers)、以及抗刺激劑(anti-irritants)等。有關這些添加劑的選用與數量是落在熟習此項技術之人士的專業素養與例行技術範疇內。 According to the present invention, the substrate may contain one or more additives selected from but not limited to the following: water, alcohols, glycol, preserving agents, antioxidants, interfaces Surfactants, absorption enhancers, stabilizing agents, pH adjusting agents, chelating agents, emulsifiers, thickeners, Solubilizing agents, penetration enhancers, anti-irritants, etc. The selection and quantity of these additives fall within the professional qualities and routine technologies of those who are familiar with this technology.
依據本發明，保養品可進一步包含有一被廣泛地使用於保養品製造技術之可接受的佐劑(acceptable adjuvant)。例如，該可接受的佐劑可包含有一或多種選自但不限於下列的試劑：溶劑、膠凝劑、活性劑、防腐劑、抗氧化劑、遮蔽劑(screening agent)、螯合劑、界面活性劑、染色試劑(coloring agent)、 增稠劑(thickening agent)、填料(filler)、香料以及氣味吸收劑。有關這些試劑的選用與數量是落在熟習此項技術之人士的專業素養與例行技術範疇內。 According to the present invention, the maintenance product may further include an acceptable adjuvant widely used in the maintenance product manufacturing technology. For example, the acceptable adjuvant may include one or more agents selected from but not limited to the following: solvents, gelling agents, active agents, preservatives, antioxidants, screening agents, chelating agents, surfactants , Coloring agent, thickening agent, filler, fragrance and odor absorber. The selection and quantity of these reagents fall within the professional qualities and routine techniques of those who are familiar with this technology.
依據本發明，保養品可利用熟習此技藝者所詳知的技術而被製造成一適合於護膚(skincare)或化妝(makeup)的形式，這包括，但不限於：水性溶液(aqueous solution)、水-醇溶液(aqueous-alcohol solution)或油性溶液(oily solution)、呈水包油型(oil-in-water type)、油包水型(water-in-oil type)或複合型之乳劑、凝膠、軟膏、乳霜、面膜(mask)、貼片、貼布(pack)、擦劑、粉末、氣溶膠、噴霧、乳液、乳漿、糊劑、泡沫、分散液、滴劑、慕斯(mousse)、防曬油(sunblock)、化妝水(tonic water)、粉底(foundation)、卸妝產品(makeup remover products)、肥皂(soap)以及其他身體清潔產品(body cleansing products)等。 According to the present invention, skin care products can be manufactured into a form suitable for skincare or makeup using techniques well known to those skilled in the art. This includes, but is not limited to: aqueous solution (aqueous solution), water -Aqueous-alcohol solution or oily solution, oil-in-water type, water-in-oil type or compound emulsion, gel Glue, ointment, cream, mask, patch, pack, wipe, powder, aerosol, spray, emulsion, emulsion, paste, foam, dispersion, drops, mousse ( mousse, sunblock, tonic water, foundation, foundation remover products, makeup remover products, soap, and other body cleansing products.
依據本發明，保養品亦可與一或多種選自但不限於下列之已知活性的外用劑(external use agents)一起合併使用：美白劑(whitening agents)[諸如維生素A酸(tretinoin)、兒茶素(catechin)、麴酸、熊果苷以及維生素C]、保濕劑、抗發炎劑(anti-inflammatory agents)、殺菌劑(bactericides)、紫外線吸收劑(ultraviolet absorbers)、皮膚營養劑(skin nutrients)、抗痘劑(anti-acne agents)、止癢劑(antipruritics)、止痛劑(analgesics)、抗皮膚炎劑(antidermatitis agents)、抗過角化劑(antihyperkeratolytic agents)、抗老化劑(antiaging agents)、抗皺劑(antiwrinkle agents)、抗皮脂溢出劑(antiseborrheic agents)、傷口治療劑(wound-healing agents)、皮質類固醇(corticosteroids)以及激素(hormones)。有關這些外用劑的選用與數量是落在熟習此項技術之人士的專業素養與例行技術範疇內。 According to the present invention, the care product can also be used in combination with one or more external use agents selected from but not limited to the following known actives: whitening agents [such as tretinoin, children Catechin, kojic acid, arbutin and vitamin C], moisturizers, anti-inflammatory agents, bactericides, ultraviolet absorbers, skin nutrients ), anti-acne agents, antipruritics, analgesics, antidermatitis agents, antihyperkeratolytic agents, antiaging agents ), antiwrinkle agents, antiseborrheic agents, wound-healing agents, corticosteroids and hormones. The selection and quantity of these external agents fall within the professional qualities and routine technologies of those who are familiar with this technology.
依據本發明，食品產品可被當作食品添加物(food additive)，藉由習知方法於原料製備時添加，或是於食品的製作過程中添加，而與任一種可食性材料配製成供人類與非人類動物攝食的食品產品。 According to the present invention, a food product can be used as a food additive, which is added during the preparation of raw materials by conventional methods, or added during the production of food, and formulated with any edible material for Food products consumed by humans and non-human animals.
依據本發明，食品產品的種類包括但不限於：飲料(beverages)、發酵食品(fermented foods)、烘培產品(bakery products)、健康食品(health foods)以及膳食補充品(dietary supplements)。 According to the present invention, the types of food products include, but are not limited to: beverages, fermented foods, bakery products, health foods, and dietary supplements.
本發明提供一種白芷發酵物用於改善皮膚外觀的用途，本發明之白芷發酵物是將白芷與溶劑以1：1-10(w/w)比例經一特定時間與溫度萃取而得之白芷萃取物，再以酵母菌、胚芽乳桿菌、及醋酸桿菌依序進行三段式發酵而獲得，其中該酵母菌為BCRC20271之菌株、該胚芽乳桿菌為BCRC910805之菌株、該醋酸桿菌為BCRC11688之菌株。本發明之白芷發酵物可有效淡化個體皮膚色斑、提升個體皮膚亮澤度、及/或提升個體皮膚保水度。 The present invention provides an application of the fermented Angelica dahuricae to improve the appearance of the skin. The Angelica fermented ferment of the present invention is an extract of Angelica dahurica extracted by extracting Angelica dahurica and solvent at a ratio of 1:1-10 (w/w) for a specific time and temperature The yeast is obtained by performing three-stage fermentation in sequence with yeast, Lactobacillus germ, and Acetobacter, wherein the yeast is a strain of BCRC20271, the Lactobacillus germ is a strain of BCRC910805, and the Acetobacter is a strain of BCRC11688. The fermented Angelica dahurica of the present invention can effectively lighten the skin spots of the individual, improve the brightness of the individual's skin, and/or enhance the water retention of the individual's skin.
同時，本發明用於改善皮膚外觀之組合物，亦可包含一有效量之白芷發酵物及一醫藥上可接受之載體，該組合物係一醫藥品、一保養品、或一食品。 At the same time, the composition for improving the appearance of the skin of the present invention may also contain an effective amount of fermented Angelica dahuricae and a pharmaceutically acceptable carrier. The composition is a medicine, a care product, or a food.
以下將詳細說明本發明白芷發酵物之詳細製備方法、該白芷發酵物淡化個體皮膚色斑之功效的測試、該白芷發酵物提升個體皮膚亮澤度之功效的測試、以及該白芷發酵物提升個體皮膚保水度之功效的測試之功效的測試，以證實本發明之白芷發酵物具有減少皮膚表皮色斑使皮膚淨透白皙、改善皮膚暗沉與枯黃的情況使皮膚透亮有光澤、以及改善皮膚乾燥與缺水的情況使皮膚水潤有彈性之功效。 The detailed preparation method of the Angelicae dahurica fermented material of the present invention, the test of the efficacy of the Angelica dahurica fermented substance to lighten the skin spots of individuals, the test of the efficacy of the Angelica dahuricae fermented substance to enhance the brightness of the skin of the individual, and the Angelica fermented substance to enhance the individual The test of the efficacy of the skin's water retention effect is to verify that the Angelica oleracea fermentation product of the present invention can reduce the skin epidermis stains, make the skin clear and fair, improve the dull and yellow skin, make the skin translucent and shiny, and improve the skin dryness. With the lack of water to make the skin hydrated and elastic.
在本發明一實施例中，將白芷的根與水、醇、或醇水混合物之萃取溶劑以1：1-10(w/w)之比例均勻混合，萃取溶劑較佳為水，並於50-100℃下同時滅菌萃取0.5-3小時後，將該萃取溶液冷卻至室溫供後續三段式發酵使用，以下列三種菌依序進行發酵：酵母菌、胚芽乳桿菌、醋酸桿菌，此三種菌之發酵順序無法前後對調，且其發酵時間比為2-6：2-9：10-30。在本發明一較佳實施例 中，首先於該萃取溶液中植入0.01-0.5%(w/w)之酵母菌(Saccharomyces cerevisiae，購買於生物資源保存與研究中心，台灣，編號為BCRC20271)，於25-35℃下進行前發酵1-2天，實際時間視發酵狀態而異。接著直接植入0.01-0.25%(w/w)之胚芽乳桿菌(Lactobacillus plantarum TCI028，專利寄存於生物資源保存與研究中心，台灣，編號為BCRC910805)，於25-35℃下進行後發酵1-3天，實際時間視發酵狀態而異。接著再直接植入1-20%(w/w)之醋酸桿菌(Acetobacter aceti，購買於生物資源保存與研究中心，台灣，編號為BCRC11688)，於25-35℃下進行深層發酵5-15天，實際時間視發酵狀態而異；其中，胚芽乳桿菌TCI028係已於中華民國專利申請號第106145146號完成專利寄存。最後在不移除此三種菌之情況下，使用設定的糖度範圍2-4°、pH<4、酒精>5%等規格，如檢驗符合該規格，則判定發酵完成並得到發酵液。接著，將該發酵液於45-70℃進行減壓濃縮，並以200-400mesh網篩過濾，再添加1-3%之檸檬酸及40-70%異麥芽寡糖調整規格後，於95-105℃下加熱70-90分鐘進行滅菌，即得到本發明之白芷發酵物。 In an embodiment of the present invention, the extraction solvent of Radix Angelicae dahurica root and water, alcohol, or alcohol-water mixture is uniformly mixed at a ratio of 1:1-10 (w/w). The extraction solvent is preferably water, and the After simultaneous sterilization and extraction at -100°C for 0.5-3 hours, the extraction solution was cooled to room temperature for subsequent three-stage fermentation, and fermentation was carried out in sequence with the following three bacteria: yeast, Lactobacillus germ, and Acetobacter. The fermentation sequence of the inoculum cannot be adjusted back and forth, and the fermentation time ratio is 2-6: 2-9: 10-30. In a preferred embodiment of the present invention, 0.01-0.5% (w/w) yeast ( Saccharomyces cerevisiae ) is first implanted in the extraction solution, purchased from the Biological Resources Conservation and Research Center, Taiwan, numbered BCRC20271, The pre-fermentation is carried out at 25-35°C for 1-2 days, the actual time varies depending on the fermentation state. Then directly implanted 0.01-0.25% (w/w) of Lactobacillus plantarum TCI028, the patent is deposited in the Biological Resources Preservation and Research Center, Taiwan, number BCRC910805), and post-fermentation is carried out at 25-35℃ 1- 3 days, the actual time varies depending on the fermentation state. Then directly implanted 1-20% (w/w) Acetobacter aceti (purchased from the Biological Resources Conservation and Research Center, Taiwan, numbered BCRC11688), followed by deep fermentation at 25-35℃ for 5-15 days The actual time depends on the fermentation state; among them, the Lactobacillus germs TCI028 series has been registered in the Republic of China Patent Application No. 106145146. Finally, without removing the three bacteria, use the set sugar content range of 2-4°, pH<4, alcohol>5% and other specifications. If the test meets the specifications, it is judged that the fermentation is completed and the fermentation broth is obtained. Next, the fermentation broth is concentrated under reduced pressure at 45-70°C, and filtered through a 200-400 mesh screen, then 1-3% citric acid and 40-70% isomalt oligosaccharides are added to adjust the specifications, at Sterilize by heating at -105°C for 70-90 minutes to obtain the Angelica fermented product of the present invention.
本發明之一實施例為測試本發明之白芷發酵物於淡化個體皮膚色斑之功效。首先，募集7位成人為受試者，每位受試者每日服用濃度5-20%(w/w)，較佳為濃度10-20%(w/w)的50mL本發明之白芷發酵物，並分別於服用前、及連續服用6週後，以VISIA肌膚檢測儀(CIS-VISIA.7 VISIA Complexion Analysis System，Canfield scientific，美國，序號V71214)進行全臉紫外線色斑檢測，使用高解析單眼相機搭配三種光源(全光域波長、紫外光及偏光波域的光源)，拍攝臉部肌膚並取得清晰圖檔後，利用專業軟體進行紫外線色斑數量分析。其中以使用前紫外線色斑數量為100%，相對於使用前所得出之百分比，為使用後之改善狀況百分比。 One embodiment of the present invention is to test the efficacy of the Angelica fermenta of the present invention in lightening the skin spots of individuals. First, recruit 7 adults as subjects, each subject taking 50mL of Angelica flavescens of the present invention at a concentration of 5-20% (w/w), preferably 10-20% (w/w) per day Before and after taking the medicine for 6 weeks, the VISA skin tester (CIS-VISIA.7 VISIA Complexion Analysis System, Canfield scientific, USA, serial number V71214) was used to detect ultraviolet spots on the entire face, using high resolution The monocular camera is equipped with three kinds of light sources (light sources in the full-optical wavelength, ultraviolet light and polarized wave domain). After capturing the facial skin and obtaining a clear image file, the professional software is used to analyze the amount of ultraviolet spots. Among them, the number of ultraviolet spots before use is 100%, and the percentage obtained before use is the percentage of improvement after use.
本發明之白芷發酵物於淡化個體皮膚紫外線色斑之結果如圖1所 示。在服用本發明之白芷發酵物6週後，比使用前減少了6.5%的皮膚紫外線色斑。此結果顯示本發明之白芷發酵物能有效淡化個體皮膚之紫外線色斑，具有減少皮膚表皮色斑使皮膚淨透白皙之功效。 The results of the Angelica oleracea fermented material of the present invention in lightening the ultraviolet spots of individual skin are shown in FIG. 1. After taking the Angelica oleracea fermented material of the present invention for 6 weeks, the skin ultraviolet stains were reduced by 6.5% compared with before use. This result shows that the fermented Angelica dahurica of the present invention can effectively lighten the ultraviolet spots of the individual skin, and has the effect of reducing the skin epidermis spots and making the skin clear and fair.
本發明之一實施例為測試本發明之白芷發酵物於提升個體皮膚亮澤度之功效。首先，募集7位成人為受試者，每位受試者每日服用濃度5-20%(w/w)，較佳為濃度10-20%(w/w)的50mL本發明之白芷發酵物，並分別於服用前、及連續服用6週後，以Queclink GL200(購自GpsGate，美國)進行全臉皮膚表面亮澤度的檢測，該儀器係專門用來測試皮膚表面的光澤度，因皮膚不僅在結構與亮度方面不同，在顏色上也有不同，因此該儀器通過測試皮膚表面的反射光和散射光，可以精確和方便地測試不同皮膚的光澤度，其平行白光係由探頭頂部的LED所產生。 One embodiment of the present invention is to test the effect of the Angelica oleracea fermented material of the present invention on enhancing the skin brightness of an individual. First, recruit 7 adults as subjects, each subject taking 50mL of Angelica flavescens of the present invention at a concentration of 5-20% (w/w), preferably 10-20% (w/w) per day Before and after taking the medicine for 6 weeks, Queclink GL200 (purchased from GpsGate, USA) was used to test the brightness of the skin on the whole face. The instrument is specially used to test the gloss of the skin surface because of The skin is not only different in structure and brightness, but also in color, so the instrument can accurately and conveniently test the gloss of different skins by measuring the reflected light and scattered light on the skin surface. Its parallel white light is led by the LED on the top of the probe Produced.
該儀器為了在一個相對較小且方便攜帶的探頭內產生一個60°的入射角，光會先以0°角射向一個平面鏡，然後反射成一個60°的入射角。兩個獨立的傳感器分別測試與入射角相同並經過一個平面鏡後的反射光和散射光。基於入射光在所有的角度方向上以同樣的方式進行散射的假定，且散射光的測試是在完全垂直於皮膚表面入射光的0°角上進行的。其中以使用前亮澤度為100%，相對於使用前所得出之百分比，為使用後之改善狀況百分比。 In order to generate an incident angle of 60° in a relatively small and portable probe, the instrument will first strike a plane mirror at an angle of 0° and then reflect it into an incident angle of 60°. Two independent sensors measure the reflected light and scattered light at the same angle of incidence and after passing through a plane mirror. Based on the assumption that the incident light is scattered in all angular directions in the same manner, and the scattered light is tested at an angle of 0° that is completely perpendicular to the incident light on the skin surface. Among them, the brightness before use is 100%, and the percentage obtained before use is the percentage of improvement after use.
本發明之白芷發酵物於提升個體皮膚亮澤度之結果如圖2所示。在服用本發明之白芷發酵物6週後，比使用前增加了5.3%的皮膚亮澤度。此結果顯示本發明之白芷發酵物能有效提升個體皮膚之亮澤度，具有改善皮膚暗沉、枯黃的情況使皮膚透亮有光澤之功效。 The results of the Angelica oleracea fermented material of the present invention in improving the skin brightness of an individual are shown in FIG. 2. After taking the Angelica Angelica fermented product of the present invention for 6 weeks, the skin brightness is increased by 5.3% compared with before use. This result shows that the fermented Angelica dahurica of the present invention can effectively enhance the brightness of the individual skin, and has the effect of improving the dull and yellow skin and making the skin translucent and shiny.
本發明之一實施例為測試本發明之白芷發酵物於提升個體皮膚 保水度之功效。首先，募集7位成人為受試者，每位受試者每日服用濃度5-20%(w/w)，較佳為濃度10-20%(w/w)的50mL本發明之白芷發酵物，並分別於服用前、及連續服用6週後，以CK Cutometer® dual MPA 580多探頭膚質分析儀(CK electronic，德國)進行皮膚保水度之檢測，使用電容測量來測量皮膚水合作用的狀態，利用探頭按壓皮膚進行測量。其中以使用前保水度為100%，相對於使用前所得出之百分比，為使用後之改善狀況百分。 One embodiment of the present invention is to test the efficacy of the Angelica oleracea fermented material of the present invention in enhancing the water retention of an individual's skin. First, recruit 7 adults as subjects, each subject taking 50mL of Angelica flavescens of the present invention at a concentration of 5-20% (w/w), preferably 10-20% (w/w) per day Before and after 6 weeks of continuous use, CK Cutometer® dual MPA 580 multi-probe skin texture analyzer (CK electronic, Germany) was used to detect skin water retention, and capacitance measurement was used to measure skin hydration. The state of the sensor is measured by pressing the skin with the probe. Among them, the water retention before use is 100%, and the percentage obtained before use is the percentage of improvement after use.
本發明之白芷發酵物於提升個體皮膚保水度之結果如圖3所示。在服用本發明之白芷發酵物6週後，比使用前大幅提升了21.4%的皮膚保水度。此結果顯示本發明之白芷發酵物能有效提升個體皮膚之保水度，具有改善皮膚乾燥、缺水的情況使皮膚水潤有彈性之功效。 The results of the Angelica fermented material of the present invention in improving the water retention of an individual's skin are shown in FIG. 3. After taking the Angelica oleracea fermented product of the present invention for 6 weeks, the skin water retention of the skin was greatly improved by 21.4% compared with before use. This result shows that the fermented Angelica dahurica of the present invention can effectively enhance the water retention of individual skin, and has the effect of improving the dryness and dehydration of the skin and making the skin moist and elastic.
綜上所述，本發明將白芷之萃取物以酵母菌、胚芽乳桿菌、及醋酸桿菌進行三段式發酵所得之白芷發酵物，能藉由該微生物發酵製程使白芷的效性物質多醣大量釋出；本發明之白芷發酵物能有效淡化個體皮膚之紫外線色斑，以減少皮膚表皮色斑使皮膚淨透白皙；能有效提升個體皮膚之亮澤度，以改善皮膚暗沉、枯黃的情況使皮膚透亮有光澤；能有效提升個體皮膚之保水度，以改善皮膚乾燥、缺水的情況使皮膚水潤有彈性。因此，本發明之白芷發酵物可用於製備改善皮膚外觀之組合物的用途，且該組合物是一醫藥品、一保養品、或一食品，可藉由口服、塗抹等方式給予一個體。 To sum up, the present invention extracts the Angelica dahurica extract by the three-stage fermentation of yeast, Lactobacillus germ, and Acetobacter, and can release a large amount of the effective substance polysaccharide of Angelica dahurica through the fermentation process of the microorganism Radix Angelicae dahurica of the present invention can effectively lighten the ultraviolet spots of individual skin to reduce skin epidermal spots and make the skin clear and fair; it can effectively improve the brightness of individual skin to improve the dull and yellow skin. The skin is translucent and shiny; it can effectively improve the moisture retention of individual skin to improve the dryness and dehydration of the skin and make the skin moist and elastic. Therefore, the fermented Angelica dahurica of the present invention can be used to prepare a composition for improving the appearance of skin, and the composition is a medicine, a care product, or a food, and can be administered to a body by oral administration, smearing, or the like.
食品工業發展研究所(台灣)；民國106年12月13日；編號BCRC910805 Food Industry Development Institute (Taiwan); December 13, 106; No. BCRC910805
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