TW201700088A - 用於淡化膚色與減少黑色素的植物萃取組合物及其醫藥品與用途 - Google Patents
用於淡化膚色與減少黑色素的植物萃取組合物及其醫藥品與用途 Download PDFInfo
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- TW201700088A TW201700088A TW104120911A TW104120911A TW201700088A TW 201700088 A TW201700088 A TW 201700088A TW 104120911 A TW104120911 A TW 104120911A TW 104120911 A TW104120911 A TW 104120911A TW 201700088 A TW201700088 A TW 201700088A
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- plant extract
- melanin
- composition
- extract composition
- resveratrol
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Abstract
本發明提供一種可用於抑制酪胺酸酶的酵素活性並減少或預防黑色素生成之植物萃取組合物及其醫藥品，其中該植物萃取組合物含有重量比例為4：1至1：4之薑黃萃取物與白藜蘆醇。本發明植物萃取組合物及其醫藥品可用於預防和治療淡化皮膚顏色及黑色素沉澱，以使受體局部部位達到皮膚顏色淡化及減少黑色素沉澱之效果。
Description
本發明關於一種植物萃取組合物，尤指藉由包含特定重量比例之薑黃萃取物與白藜蘆醇的植物萃取物；本發明更關於一種包含有前述組合物之醫藥品，尤指可用於預防和治療淡化皮膚顏色及黑色素沉澱之醫藥品；本發明更關於一種用途，尤指藉由前述醫藥品用於預防和治療淡化皮膚顏色及黑色素沉澱的用途。
皮膚的顏色主要受到黑色素(melanin)含量的多寡而決定，正常而言皮膚中的黑色素可做為人體的自然保護屏障，黑色素的存在是有助於人類抵抗紫外線輻射、避免光致癌性(photocarcinogenesis)的風險；反之過量而形成黑色素的沉澱(pigmentation)則會造成許多的困擾，例如老人斑、雀斑、黑斑、肝斑等皮膚所不需要的色素沉澱，亦或傷口癒合過程所產生的色素沉澱。黑色素是由存在於表皮層的黑色素細胞(melanocytes)所生成，並藉由黑色素細胞的樹突狀構造將所形成的黑色素體(melanosome)轉移到角質細胞(keratinocytes)中。不同人種之間其黑色素細胞的數量差異不大，而主要影響膚色差異的因素也就是黑色素比例、存在於角質細胞中黑色素體的多寡及其分佈。
刺激黑色素生成的因素包含直接受到紫外線
照射或經由角質細胞所分泌的黑色素細胞刺激激素(α-MSH)作用，進而促進酪胺酸酶的酵素反應而產生黑色素。目前所熟知的黑色素生成機制是透過酪胺酸酶(tyrosinase)酵素的作用將酪胺酸(tyrosine)經過多步驟的反應轉換而成。整個反應的過程中，每個步驟都需要酪胺酸酶的參與，首先酪胺酸酶會把細胞中的酪胺酸轉變成L-多巴(L-DOPA)，再接著將L-DOPA轉變為L-多巴醌(L-dopaquinone)，並持續經酪胺酸酶的作用形成個階段的中間產物，包含多巴色素(dopachrome)、5,6-二羟基吲哚(5,6-dihydroxyindole)及吲哚-5,6-醌(indole-5,6-quinone)，經由一連串的反應過程後最終產生黑色素(melanin)。因此，可將酪胺酸酶視為主要負責調節人類黑化反應(melanization)以及黑色素生成的關鍵酵素，同時調節酪胺酸酶的活性亦是目前普遍被應用在減少黑斑及促進皮膚美白的主要研發方向。此外，皮膚因受傷發炎而造成的色素沉澱(post-inflammatory hyperpigmentation,PIH)則是另一項促使黑色素生成並轉移到角質細胞的原因，一般而言PIH可分為表皮色素沉澱(epidermal PIH)與真皮色素沉澱(dermal PIH)兩類。當在表皮層發生發炎反應時，花生四烯酸(arachidonic acid)分別受到環氧酵素(cyclooxygenase)、脂肪氧化酵素(lipoxygenase)的作用而生成前列腺素(prostaglandins E2,PGE2)、白三烯素(leukotriene,LTC4)，而黑色素細胞受到此類的發炎因子刺激後，會促進黑色素的大量生成並轉移到周邊的角質細胞中。另一方面，當位於表皮與真皮交界處的基底層(basal cell layer)受到發炎反
應的破壞時，大量的黑色素會受到真皮層的巨噬細胞所吞食(melanophages)，因而產生較深層的暗棕色或藍灰色沉澱。在生活中例如青春痘、水痘、帶狀泡疹、皮膚炎或任何因傷口而造成的皮膚發炎反應，都可能會是造成PIH的產生原因。
目前被用於抑制黑色素生成或是淡化黑色素的美白成分，包含維生素C磷酸鎂鹽(magnesium ascorbyl phosphate)、維生素C磷酸鈉鹽(sodium ascorbyl phosphate)、維生素C醣苷(ascorbyl glucoside)、麴酸(kojic acid)、熊果素(arbutin)、鞣花酸(ellagic acid)、洋甘菊精(chamomile ET)、二丙基聯苯二醇(5,5'-dipropyl-biphenyl-2,2'-diol)、傳明酸(tranexamic acid)、甲氧基水楊酸鉀(potassium methoxysalicylate)以及對苯二酚(hydroquinone)等許多成份被提出可用以抑制黑色素形成或減少皮膚黑色素沈澱或淡化膚色。
維生素C的金屬鹽類與醣化衍生物都是藉由抗氧化的方式，在酪胺酸酶的反應過程中將黑色素的中間產物L-dopaquinone進行還原，達到抑制黑色素生成的效果，維生素C本身安全性高且可以防止自由基的形成，但安定性不佳極易被氧化，因此透過與金屬結合或醣化作用可以增加其穩定性，這類成分包含維生素C磷酸鎂鹽、維生素C磷酸鈉鹽、維生素C醣苷。因為酪胺酸酶是一種以二價銅離子為活性中心的氧化酵素，因此會與銅離子結合或競爭的結構也被開發用於抑制酪胺酸酵素，進而阻斷黑色素生成，這類的代表物質為麴酸。麴酸是藉由本身的結
構與酪胺酸酶的銅離子結合使其酵素活性降低，進而影響酪胺酸轉化為L-DOPA及L-dopaquinone的反應過程。另外一類是競爭取代酪胺酸酶的作用受質，例如熊果素，這類物質可以與酪胺酸競爭，使酪胺酸酶的作用受質減少。或者利用對苯二甲酚所產生的自由基直接黑色素細胞產生細胞毒性，但不當使用可能會造成皮膚刺激、皮膚炎、異常的色素沉澱及皮膚反黑等副作用，而對苯二甲酚也已被列為藥用成分在化妝品中不得添加，藥用的含量也不得超過5%。
各成分透過不同的機制達到美白的效果，也藉由不同的機制達到淡化膚色的目的，然而在美白的機制方面不外乎包含阻斷酪胺酸酶來減少黑色素的生成、阻斷黑色素體自黑色素細胞轉移到角質細胞、抑制酪胺酸酶的活性、促進黑色素在角質細胞的代謝或使用預防性的方式隔離紫外線。過去亦有使用各種成分，如維生素C、傳明酸、維生素B群等，以靜脈注射的方式企圖達到去斑或美白效果的治療手段，然而這樣的給藥方式及美白用途，並未在任何一個國家合法上市，且其美白效果並不明顯，也可能會有過敏的風險。另外，若是其產品滅菌不完全或注射時消毒不完全，更會有極高的風險產生靜脈炎、蜂窩性組織炎、敗血症等嚴重的副作用。
雖然過去市場上對於美白相關的產品開發不曾間斷，但消費者對於去斑及膚色淡化的需求始終不曾停止，且美白相關的技術或產品市場亦日漸增加，然而目前所使用的各式成份在淡化或去除黑色素上的效果卻仍有更
上層樓的空間。因此尋找更安全並且具有抑制黑色素的活性成分更是目前廣大的醫學美容市場上引頸期盼且不可或缺的。
另外，過去在開發美白相關應用的成分或產品
時，大部分實驗會先添加藥物後，再給予α-MSH刺激黑色素生成，然後去比較添加藥物組別的黑色素抑制效果；或是僅進行體外試管反應，直接將藥物和酪胺酸混合，再添加酪胺酸脢去比較其活性抑制的程度；這樣的作法因為與體內實際產生黑色素的情況先後順序不同，因此即使實驗效果不錯，後續實際應用於美白產品後的美白療效往往遠不如預期。
鑑於現有技術並未有安全且具有抑制黑色素的活性成分以及現有技術之試驗方法皆為先給藥再刺激黑色素生成，而與體內實際產生黑色素的情況先後順序不同的問題，本發明的目的在於提供一種包含有特定重量比例之薑黃萃取物與白藜蘆醇的植物萃取組合物，即使在已誘導黑色素生成的情況下，仍可顯著抑制酪胺酸酶的酵素活性，以達成減少或預防黑色素生成之效果。
為達到上述目的，本發明提出一種含有薑黃萃取物與白藜蘆醇的植物萃取組合物，可用於抑制酪胺酸酶的酵素活性並減少或預防黑色素生成，其中薑黃萃取物與白藜蘆醇之重量比例為4：1至1：4。
較佳的，所述之薑黃萃取物與白藜蘆醇之重量比例為3：2。
依據本發明，「薑黃萃取物」於此處係指包含薑黃素之萃取物，其中薑黃素佔薑黃萃取物之濃度為85%至100%。
本發明更提供一種包含有前述組合物之醫藥品，其中醫藥品包含前述用於淡化皮膚顏色以及預防及治療黑色素沉澱之有效劑量之植物萃取組合物以及其醫藥學上可接受的載劑。
依據本發明，「有效劑量」係指在劑量上及對於所需要之時間而言對達成所要抑制酪胺酸酶活性及抑制黑色素生成有效之量；其如本發明所例示者，有效抑制酪胺酸酶活性及抑制黑色素生成劑量可透過抑制黑色素生成實驗及抑制酪胺酸酶活性試驗而得知。
依據本發明，所述之醫藥品可用現有技術水準中已習知之方法，利用已知之賦形劑，如黏合劑、崩散劑、分散劑、充填劑、安定劑、稀釋劑及染劑加以製造。較佳的，所述之「醫藥學上可接受之賦形劑」包括生理上相容人體之任意及所有溶劑、分散介質、抗菌劑及抗真菌劑、等張劑及吸收延緩劑及其類似物。藥學上可接受之載劑的實例包括水、鹽水、磷酸鹽緩衝生理食鹽水、右旋糖、甘油、乙醇及其類似物的一或多種及其組合。在許多情況中，較佳的組合物包括等張劑，例如糖、諸如甘露醇、山梨糖醇之多元醇或氯化鈉。藥學上可接受之載劑可進一步包含微量輔助物質，諸如濕潤劑或乳化劑、防腐劑或緩衝劑。
本發明所述之醫藥品可以多種形式存在，該等形式包括，但不限於液體、半固體及固體藥劑形式，其中
液體溶液(例如可注射及可輸注溶液)包括分散液或懸浮液；固體藥劑包括，但不限於錠劑、丸劑、粉劑、脂質體及栓劑。較佳的形式取決於預期的投藥模式及治療應用；較佳的，本發明所述之醫藥品之劑型是口服、輸注溶液或局部外用製劑形式。更佳的，本發明之醫藥品係被製造成適合於皮下注射劑或輸注溶液，且係以皮下注射或靜脈注射方式予以施用。更佳的，本發明之醫藥品係被製造成適合於局部地施用於皮膚上的外用製劑(external preparation)，其劑型包括，但不限於：乳劑(emulsion)、凝膠(gel)、軟膏(ointment)、乳霜(cream)、貼片(patch)、擦劑(liniment)、粉末(powder)、氣溶膠(aerosol)、噴霧(spray)、乳液(lotion)、乳漿(serum)、糊劑(paste)、泡沫(foam)、滴劑(drop)、懸浮液(suspension)以及油膏(salve)。
更佳的，本發明所述之醫藥品作為外部製劑時，可使用添加劑，其添加劑包括，但不限於水、醇(alcohols)、甘醇(glycol)、碳氫化合物(hydrocarbons)[諸如石油膠(petroleum jelly)以及白凡士林(white petrolatum)]、蠟(wax)[諸如石蠟(paraffin)以及黃蠟(yellow wax)]、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)、膠凝劑(gelling agents)[諸如微結晶纖維素(microcrystalline cellulose)以及羧基甲基纖維素(carboxymethylcellulose)]、活性劑(active agents)、保濕劑(humectants)、氣味吸收劑(odor absorbers)、香料(fragrances)、pH調整劑(pH adjusting
agents)、螯合劑(chelating agents)、乳化劑(emulsifiers)、閉塞劑(occlusive agents)、軟化劑(emollients)、增稠劑(thickeners)、助溶劑(solubilizing agents)、滲透增強劑(penetration enhancers)、抗刺激劑(anti-irritants)、著色劑(colorants)以及推進劑(propellants)；添加劑的種類選用及用量是本領域熟悉技術人士之例行技術範疇內。
本發明更提供一種前述植物萃取組合物用於製備淡化皮膚顏色及預防和治療黑色素沉澱之醫藥品的用途，其係將包含有植物萃取組合物之醫藥品以有效劑量施予受體局部部位，以使受體局部部位達到皮膚顏色淡化及減少黑色素沉澱之效果。
較佳的，所述之受體包括，但不限於動物或人類。
較佳的，所述之施予方式包括，但不限於口服施予、局部注射施予或外用塗抹。
較佳的，所述之將醫藥品以口服方式施予受體之有效劑量係介於受體每公斤1毫克(mg/KG)至50mg/KG。
較佳的，所述之將醫藥品以局部注射或靜脈注射給藥施予受體之有效劑量係介於0.01mg/KG至2mg/KG。
較佳的，所述之將醫藥品以外用塗抹方式施予受體之有效劑量之濃度係介於0.01%至10%。
本發明所述之植物萃取組合物經媒劑調配後更可製成皮膚護理品或化妝品以供外用塗抹；較佳的，媒劑包括，但不限於乳液(例如水包油及油包水乳液)、乳霜
(cream)、化妝水(lotion)、溶液(例如水性溶液或水-酒精溶液)、無水基劑(例如唇膏或粉劑)、泡沫體、凝膠、水凝霜、面膜片體、噴霧劑及膏劑。
本發明所述之植物萃取組合物及包含其植物萃取組合物之醫藥品可用於皮膚顏色淡化及黑色素沉澱的預防和治療，且包含，但不限於不期望的色素沉澱和異常的色素沉澱，例如老人斑、肝斑、雀斑、發炎或創傷所造成的過度色素沉澱、日曬後的色素沉澱等。且本發明所使用的植物萃取組合物成分安全性高，經由實施例證明不會對細胞存活率產生影響，而本發明所述之植物萃取組合物即使在先使用α-MSH刺激黑色素生成後再給藥的狀況下，仍然能有效的降低黑色素的含量，在此模式下更可反映出皮膚已受到刺激而產生黑色素沉澱的皮膚狀況，在使用本發明之植物萃取組合物後可以有效減少黑色素達到淡化膚色或去斑的效果。
圖1是以熊果素(arbutin)、白藜蘆醇(resveratrol)、薑黃素(curcumin)以及本發明所述之組合物AW-001-C2、AW-001-C3、AW-001-C5及AW-001-C7相較於控制組(DMEM)對於小鼠黑色素瘤細胞B16-F10之細胞存活率分析柱狀圖。
圖2A是以熊果素、白藜蘆醇、薑黃素以及本發明所述之組合物AW-001-C2、AW-001-C3、AW-001-C5及AW-001-C7相較於控制組(α-MSH)對於小鼠黑色素瘤細胞
B16-F10之黑色素生成量比較之柱狀圖；圖2B是以熊果素、白藜蘆醇、薑黃素以及本發明所述之組合物AW-001-C2、AW-001-C3、AW-001-C5及AW-001-C7對於小鼠黑色素瘤細胞B16-F10之黑色素生成抑制率之柱狀圖。
圖3A是以熊果素、白藜蘆醇、薑黃素以及本發明所述之組合物AW-001-C2、AW-001-C3、AW-001-C5及AW-001-C7相較於控制組(α-MSH)對於小鼠黑色素瘤細胞B16-F10之酪胺酸酶活性比較之柱狀圖；圖3B是以熊果素、白藜蘆醇、薑黃素以及本發明所述之組合物AW-001-C2、AW-001-C3、AW-001-C5及AW-001-C7對於小鼠黑色素瘤細胞B16-F10之酪胺酸酶活性抑制率之柱狀圖。
本發明將由下列的實施例做為進一步說明，這些實施例並不限制本發明前面所揭示的內容。熟習本發明之技藝者，可以做些許之改良與修飾，但不脫離本發明之範疇。
本發明所述之組合物之各成分之重量比例：
組合物AW-001-C2薑黃萃取物：白藜蘆醇=4：1
組合物AW-001-C3薑黃萃取物：白藜蘆醇=1：4
組合物AW-001-C5薑黃萃取物：白藜蘆醇：槲黃素=2：0：3
組合物AW-001-C7薑黃萃取物：白藜蘆醇=3：2
實施例1. 細胞存活率測試
本實施例之目的為確認植物萃取物及發明組合物添加後對細胞存活之影響。本實施例使用小鼠黑色素瘤細胞B16-F10，試驗組別共8組，分別為控制組(DMEM)、熊果素(arbutin)、白藜蘆醇(resveratrol)、薑黃素(curcumin)以及本發明所述之組合物AW-001-C2、AW-001-C3、AW-001-C5及AW-001-C7，每組實驗進行3重複，並以流式細胞儀進行存活率分析。
將1x105顆細胞接種於6孔細胞盤(6 well plate)，培養24小時後分別添加濃度為250ppm熊果素、濃度為6ppm白藜蘆醇、濃度為8ppm薑黃素以及濃度分別為8ppm之組合物AW-001-C2、AW-001-C3、AW-001-C5及AW-001-C7處理細胞48小時，再以Trypsin-EDTA將細胞收集下來並計數5x105顆細胞放入流式管(flow tube)中。離心去除上清液，並以PBS重複清洗兩次後藉由碘化丙啶(propidium iodide,PI)染色，並以流式細胞儀收集10000顆細胞分析PI表現量。
圖1結果顯示經上述各組處理小鼠黑色素瘤細胞B16-F10後並不會影響B16-F10細胞的存活率，單一植物萃取物或本發明組合物AW-001-C2、AW-001-C3、AW-001-C5及AW-001-C7的細胞存活率與控制組相比，在統計上皆無顯著差異。表示本發明組合物或單一植物萃取物皆不會造成黑色素細胞死亡。
實施例2. 抑制黑色素生成實驗(先誘導黑色素生成再給藥)
本實施例比較單一植物萃取物及本發明所述之植物萃取組合物對於抑制黑色素生成的能力，本實施例使用小鼠黑色素瘤細胞B16-F10，試驗組別共8組，分別為控制組(α-MSH)、熊果素、白藜蘆醇、薑黃素以及本發明組合物AW-001-C2、AW-001-C3、AW-001-C5及AW-001-C7，每組實驗進行3重複，量測各組的黑色素含量。
將2x105顆細胞接種於6 well plate，培養24小時後加入每毫升10奈克(ng/ml)α-MSH作用30分鐘後，除控制組外，各組再分別添加濃度為250ppm熊果素、濃度為6ppm白藜蘆醇、濃度為8ppm薑黃素以及濃度分別為8ppm的AW-001-C2、AW-001-C3、AW-001-C5及AW-001-C7培養48小時，之後於20℃以120g離心5分鐘收取細胞，並將細胞回溶於濃度為1N氫氧化鈉(NaOH)(含10% DMSO)，均勻充分混合後將樣品至於加熱盤以80℃加熱1.5小時，待樣品冷卻後以多功能微孔盤分析儀(SpectraMax® M2e Multimode Microplate Reader)於波長475奈米(nm)量測吸光值並計算黑色素的生成抑制率。
由圖2結果可觀察到黑色素含量在各試驗組別中皆受到抑制，單一植物萃取物對抑制黑色素雖有影響，但本發明組合物AW-001-C2或AW-001-C7對於黑色素生成的抑制效果可達到顯著優於單一植物萃取物白藜蘆醇或薑黃素的抑制效果，且其抑制效果亦顯著優於熊果素。在本發明組合物中，組合物AW-001-C2、AW-001-C3與AW-001-C7皆能有效的減少黑色素生成；相較於控制組，
組合物AW-001-C2、AW-001-C3與AW-001-C7減少黑色素生成的比率分別為63.5%、24.2%及56.1%，其中組合物AW-001-C5對黑色素抑制並沒有影響，與控制組相比沒有差異，而控制組AW-001-C2及AW-001-C7對黑色素抑制的效果最佳，且其抑制效果優於濃度為250ppm的熊果素。換算各組別對黑色素的抑制率後，可推算組合物AW-001-C2及AW-001-C7與常見的美白成分熊果素相比，在相同濃度時組合物AW-001-C2及AW-001-C7對黑色素的抑制率優於熊果素76.2倍及68.7倍。
實施例3. 抑制酪胺酸酶活性實驗(先誘導黑色素生成再給藥)
本實施例藉由量測L-DOPA轉變成dopaquinone的量，加以評估並比較單一植物萃取物及不同的發明組合物抑制酪胺酸酶活性的能力。本實施例使用小鼠黑色素瘤細胞B16-F10並分為8組，分別為控制組(α-MSH)、熊果素、白藜蘆醇、薑黃素以及本發明組合物AW-001-C2、AW-001-C3、AW-001-C5及AW-001-C7，量測各組的酪胺酸梅的酵素活性。
將2x105顆細胞接種於6 well plate，培養24小時後加入10ng/ml α-MSH作用30分鐘後，除控制組外，各組再分別添加濃度為250ppm熊果素、濃度為6ppm白藜蘆醇、濃度為8ppm薑黃素以及濃度分別為8ppm AW-001-C2、AW-001-C3、AW-001-C5、AW-001-C7培養48小時，之後以Trypsin-EDTA將細胞收集下並以PBS清洗，並以含有1% Triton X-100和0.1毫莫耳濃度(mM)苯甲基磺
醯氟(phenylmethanesulfonylfluoride,PMSF)的0.1莫耳濃度(M)PBS(pH 7.0)萃取細胞中的酪胺酸酶蛋白，並加以定量，定量後取30微克(μg)與每毫升0.4毫克(mg/ml)的L-DOPA混合，以微孔盤分析儀於波長405nm量測吸光值的變化，測定1小時每10分鐘記錄1次吸光值。
圖3結果顯示，於第60分鐘時的酪胺酸酶活性，與控制組相比，熊果素、白藜蘆醇或薑黃素及本發明組合物AW-001-C2、AW-001-C3與AW-001-C7皆有減少酪胺酸酶活性的效果；而相較之下本發明組合物抑制酪胺酸酶活性的能力更顯著優於單一植物萃取物白藜蘆醇或薑黃素，亦顯著優於熊果素；本發明組合物AW-001-C2、AW-001-C3與AW-001-C7相較於控制組，其抑制酵素活性的比率分別為42.2%、24.7%及39.1%，而其中組合物AW-001-C5對酪胺酸酶活性並沒有影響，與控制組相比沒有差異，而組合物AW-001-C2及AW-001-C7對酵素活性的抑制效果最佳。換算各組在相同濃度對於酪胺酸酶活性的抑制率後，可發現組合物AW-001-C2及AW-001-C7與常見的美白成分熊果素同劑量相比，AW-001-C2及AW-001-C7對於酪胺酸酶活性的抑制率優於熊果素45.6倍及37.4倍，本結果也與實施例2所述之黑色素生成抑制試驗中所觀察到的趨勢具一致性。
Claims (9)
- 一種可用於抑制酪胺酸酶並減少或預防黑色素生成之植物萃取組合物，其中該植物萃取組合物含有重量比例為4：1至1：4之薑黃萃取物與白藜蘆醇。
- 如請求項1所述之植物萃取組合物，其中薑黃萃取物與白藜蘆醇之重量比例為3：2。
- 一種用於淡化皮膚顏色以及預防及治療黑色素沉澱之醫藥品，其包含有效劑量之如請求項1或2所述之植物萃取組合物以及其醫藥學上可接受的載劑。
- 一種如請求項1或2所述之植物萃取組合物用於製備淡化皮膚顏色及預防及減少黑色素沉澱之醫藥品的用途，其係將醫藥品以有效劑量施予受體局部部位，以使受體局部部位達到皮膚顏色淡化及減少黑色素沉澱之效果。
- 如請求項4所述之用途，其中受體係動物或人類。
- 如請求項4所述之用途，其中施予方式係口服施予、局部注射施予、靜脈注射施予或外用塗抹。
- 如請求項6所述之用途，其中將醫藥品以口服方式施予受體之有效劑量係介於受體每公斤1毫克(mg/KG)至50mg/KG。
- 如請求項6所述之用途，其中將醫藥品以局部注射或靜脈注射施予受體之有效劑量係介於0.01mg/KG至2mg/KG。
- 如請求項6所述之用途，其中將醫藥品以外用塗抹方式施予受體之有效劑量之濃度係介於0.01%至10%。
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| TW104120911A TWI605832B (zh) | 2015-06-29 | 2015-06-29 | Plant extract composition for desalinating skin and reducing melanin, pharmaceuticals and uses thereof |
Country Status (2)
| Country | Link |
|---|---|
| US (1) | US20160374911A1 (zh) |
| TW (1) | TWI605832B (zh) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP3711752B1 (en) * | 2017-12-20 | 2022-07-20 | Hanyi Bio-Technology Company Ltd. | Use of cannabidiol or cannabis extract in a cosmetic method of skin whitening |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FR2949044B1 (fr) * | 2009-08-12 | 2021-05-07 | Expanscience Lab | Composition comprenant une fraction d'insaponifiable |
| US20140287071A1 (en) * | 2013-01-17 | 2014-09-25 | Lifevantage Corporation | Veterinary supplements |
| EP3010481B1 (en) * | 2013-06-19 | 2020-04-29 | ELC Management LLC | Methods, compositions, and kit for whitening hyper pigmented spots on skin |
-
2015
- 2015-06-29 TW TW104120911A patent/TWI605832B/zh active
-
2016
- 2016-06-24 US US15/191,899 patent/US20160374911A1/en not_active Abandoned
Also Published As
| Publication number | Publication date |
|---|---|
| US20160374911A1 (en) | 2016-12-29 |
| TWI605832B (zh) | 2017-11-21 |
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