TW201345541A - 含有薑萃取物之口腔用組成物及相關方法 - Google Patents
含有薑萃取物之口腔用組成物及相關方法 Download PDFInfo
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Abstract
本發明敘述包含萃取物組合物之組成物,及製備與使用彼等之方法。
Description
本申請案請求2010年12月4日申請之美國專利臨時申請案No.61/266,685之優先權,將其併入本文以資參考。
本發明敘述包含萃取物組合物之組成物,及製備與使用彼等之方法。
潔牙劑組成物被廣泛使用以提供口腔健康。呈牙膏、漱口水、口香糖、爽口片、粉劑、泡沫劑等之潔牙劑已與各式各樣提供使用者一些好處之活性物質一起調配。彼等好處為抗菌、消炎、與抗氧化劑等性質。潔牙劑之彼等性質使其成為有用之治療劑以預防或治療例如蛀牙、牙齦炎、牙菌斑、牙石、牙周病等若干口腔健康狀況。
牙齦炎乃支撐牙齒之牙齦及齒槽骨發炎或感染。一般認為牙齦炎係由口中之細菌(特別是指使形成牙菌斑之細菌)及細菌之副產物形成之毒素所引致,及相信毒素指使口內之口腔組織發炎。相較於牙齦炎,牙周炎是一種日益惡化之疾病狀態,其
中牙齦發炎並開始萎縮及形成牙周袋,最後可能導致骨骼與牙周韌帶之破壞。支撐齒列結構之細菌性感染可包括牙齦炎與牙周炎,惟亦可包括骨骼(例如由於手術治療之顎骨)感染。再者,口腔組織發炎可能由手術、局部損傷、創傷、壞死、不適當之口腔衞生或各種全身性起源引起。
一般認為彼等疾病及症狀所牽連之細胞成分包括上皮組織、牙齦纖維母細胞、與循環之白血球,所有彼等均促成宿主對細菌產生的致病因子之反應。與彼等口腔感染有牽連最常見之細菌病原體為鏈球菌屬(Streptococci spp.)[例如,轉糖鏈球菌(S.mutans)]、卟啉單胞菌屬(Porphyromonas spp.)、放線桿菌屬(Actinobacillus spp.)、類桿菌屬(Bacteroides spp.)、葡萄球菌屬(Staphylococci spp.)、具核梭桿菌(Fusobacterium nucleatum)、小韋榮球菌(Veillonella parvula)、內氏放線菌(Actinomyces naeslundii)、與牙齦卟啉單胞菌(Porphyromonas gingivalis)。雖然細菌感染常為這許多口腔疾病致病之起因,惟疾病之發病機制係由宿主反應所媒介。循環之多形核嗜中性白血球(PMNs)為感染部位所見活動過度之主要原由。典型地,PMNs及炎症之其他細胞介質變得功能亢進且釋放毒性化學物質,彼等為感染病灶周圍組織破壞之部分原由。
因此,口腔組織之細菌感染激發宿主之免疫反應,並藉由向上調控引起重大組織傷害之炎性介質而削弱癒合過程。被廣泛研究其對炎性反應之影響之一類介質為花生油酸代謝物,亦即前列腺素與白三烯素,彼等係經由環加氧酶或脂肪加氧酶酵素路徑產生。彼等代謝物已被牽連為牙齦炎、牙周炎、骨髓炎及
其他炎性疾病之首要介質。
各式各樣組成物見述於此項技藝中以預防及治療由於細菌感染之口腔發炎。特別是,為了防止衍生自花生油酸路徑之炎性介質之堆積,已成功使用非類固醇消炎藥物(NSAIDs)治療罹患由花生油酸代謝物引起的牙周病及炎性疾病之病患。實驗性與臨床數據已證實消炎痛(indomethacin)、氟比洛芬酯(flurbiprofen)、酮洛芬(ketoprofen)、依布洛芬(ibuprofen)、奈普生(naproxen)、與甲氯胺苯酸(meclofenamic acid)對於齒槽骨流失,及牙科疾病模式中前列腺素與三烯素減少具顯著改善作用。然而,經常使用NSAIDs之一主要缺點為可能逐漸產生胃灼熱、胃潰瘍、胃腸道出血、及毒性。
其他治療方法包括使用抗菌療法與抗生素消除潛在之感染。彼等治療之作用在於減少刺激源(細菌),惟影響宿主對細菌分泌毒素之免疫反應之速度慢。此外,特定抗生素及其他抗菌療法可能引致口腔黏膜潰瘍、誘發脫屑性牙齦炎、變色、長期使用後潛在之抗生素抗性,而且由於刺激使組織發炎惡化。
潔牙劑組成物中已使用精油,主要作為調味劑用。許多精油為植物之油,惟植物油之組成與該植物之萃取物有很大不同。
薑(Zingiber officinale)自古以來即具醫療用途,其具有據稱可用於廣泛範圍病痛之廣泛範圍性質。有關薑之消炎、鎖痛、解熱、抗菌及降血糖等活性已被探討。Mascolo,N.,et al.,“Ethnopharmacologic Investigation of ginger(Zingiber officinale),J.Ethnopharmacol.,27,pp.129-140(Nov.1989)。據報導薑對四種呼
吸道病原體[金黃葡萄球菌(Staphylococcu aureus)、化膿性鏈球菌(Streptococcus pyogenes)、肺炎鏈球菌(Streptococcus pneumoniae)、與流感嗜血桿菌(Haemophilus influenzae)]呈現抗細菌效力。Akoachere,J.F.,et al.,“Antibacterial effect of Zingiber officinale and Garcinia kola on respiratory tract pathogens,”East Afr.Med.J.,79,pp 588-592(Nov.2002)。薑之特定成分,詳言之,薑油,據報導對口腔細菌具抗菌活性。Park,et al.,“Antibacterial activity of (10)-Gingerol and(12)-Gingerol isolated from Ginger Rhizome against periodontal bacteria,”J.Phytother.Res.,22(11),pp.1446-1449,(Nov.2008)。據報導薑之若干萃取物具抗真菌活性。Atai,et al.,“Inhibitory Effect of Ginger Extract on Candida albicans,”Am.J.App.Sciences,6(6),pp.1067-1069(2009)。
美國專利案Nos.6,264,926與7,083,779揭示含薑之若干牙粉不是很具效力,且對牙齦與牙齒可能有害,以及有毒性。美國專利案No.4,423,030揭示一種利用溶劑萃取薑之乾燥地下莖製備之高刺激油性樹脂,於牙科用乳膏或漱口藥中可作為精油調味劑用。
美國專利申請公告案No.2009/0131364揭示具生物活性之薑萃取物,係用於治療氧化壓力引發之疾病,例如潰瘍。美國專利申請公開案No.2007/011652揭示含有植物性萃取物之紅牙粉,其中可能包含薑萃取物。其他文獻揭示各種薑萃取物之抗真菌、消炎、或其他有益健康之作用。參見,例如,美國專利案Nos.6,946,153與6,274,177、及美國專利申請公開案No.2009/0104293。
雖然一些報導指出使用薑萃取物有益健康,惟除了可能作為味道增強劑外,彼等用途並未建議薑萃取物與其他天然萃取物組合可提供任何口腔保健利益。業界對於提供口腔抗細菌、消炎、以及抗氧化劑作用之天然補充物之提供有所需求。
頃發現於各種潔牙劑組成物中添加薑萃取物可產生適用於治療及預防包括牙齦炎、牙菌斑積聚等種種口腔疾病之牙膏、漱口水、口香糖、牙貼(mouth strips)、珠粒、及他組成物。一般相信薑萃取物含有不同量之,尤其是,一或多種畢沙波林(bisaboline)、桉油醇、水芹烯、檸檬醛、龍腦、香茅醛、香葉醛、沈香醇、檸檬烯、薑醇、薑鹼、莰烯、薑油、薑烯酚、去氫薑二酮、薑酮、生薑蛋白酶、維生素B6、維生素C、鈣、鎂、磷、鉀、亞麻油酸、黏膠質性多醣類(鼠李糖、阿拉伯糖、木糖、甘露糖、半乳糖、葡萄糖等)、沒食子酸、單寧酸、龍膽酸、原兒茶酸、香草酸、咖啡酸、丁香酸、肉桂酸、與其混合物,及可於潔牙劑組成物中添加其他有益化學物質,俾使於使用時傳送至口腔之量可有效地提供抗細菌、抗氧化劑、及/或消炎作用。於各種具體實例中,係使薑萃取物之諸成分組合薑萃取物以外之其他天然萃取物,以提供增強之活性。
頃發現以薑萃取物調配之潔牙劑,組合其他天然萃取物,展現抗菌、消炎、及/或抗氧化劑性質,而且不需附加抗細菌劑即具治療口乾症之效力。
根據具體實例之特徵,係提供包含薑萃取物、口腔
可接受之載體、及除了薑萃取物以外之天然萃取物之口腔用組成物。具體實例之另一特徵,係提供治療口腔軟組織之方法,該方法包括投與包含薑萃取物、口腔可接受之載體、及除了薑萃取物以外之天然萃取物之組成物至口腔中之軟組織。
從下文提供之詳細說明,本發明之進一步應用領域將成為明顯易見。必須瞭解的是,該詳細說明及特定實例,雖然指示本發明之較佳具體實例,惟僅供說明用途而不擬對本發明範圍構成侷限。
於整個說明書中,範圍係用以敘述在該範圍內之每一數值之簡單表示法。在該範圍內之任何數值均可被選定以為該範圍之界限。此外,本文引用之所有參考文獻,其全部內容併入本文以資參考。於本文揭示內容之界定與引用文獻相抵觸時,由本發明揭示內容主控。此外,組成物及方法可含有,或(實質上)由本文中敘述之元件組成。
除非另行指明,否則本文及本說明書他處所示所有百分比與用量應被瞭解為係指重量百分比。所示用量係根據該物質之活性重量。本文所列舉之特定數值意欲表示該數值加減一定程度之變異性(視為測量誤差)。例如,10%之量可包括9.5%或10.5%,所示測量之誤差程度應為具有一般此項技藝者所察知及瞭解。
本文所用之“抗細菌活性”於本文中意指利用任何普遍被接受之活體外或活體內抗細菌測定法或試驗測定之活性。“消炎活性”於本文中意指利用任何普遍被接受之活體外或活體內測定法或試驗,例如抑制前列腺素生產或環加氧酶活性之測定法或試
驗測定之活性。“抗氧化劑活性”於本文中意指利用任何普遍被接受之活體外或活體內抗氧化劑測定法或試驗測定之活性。
本文中之“口腔表面”涵蓋口內之任何軟或硬表面,包括舌頭、硬與軟顎、頰黏膜、牙齦等之表面及牙齒表面。本文中之“牙齒表面”係天然牙齒表面或人工齒列(包括牙冠、牙套、補牙、牙橋、假牙、植牙等)之硬表面。本文中關於“抑制”症狀(例如口腔組織發炎)涵蓋防止、壓制、一定程度或強烈減少、或改善該症狀。
本文所用之“天然萃取物”一詞代表自天然來源(例如植物、水果、樹等)獲得之任何萃取物。天然萃取物之非限制實例包括牛膝草、木蘭、迷迭香、山茶(Camellia)屬、桑色素、肉荳蔻(Myristica fragrans)、洋棗(Zizyphus joazeiro)、石榴(Punica granatum)、山竹(Garcinia mangostana L.)、橙枳、印度苦楝(Azadirachta indica)、阿拉伯膠、烏龍茶、胡桃(Juglans regia)、竹葉花椒(Zanthoxylum alantum)、牛油果(Mimusops elengi)、黃葵(Hibiscus abelmoschus)、阿育吠陀(Ayurvedic)印度草藥、長楝樹(Carapa procera)、非洲楝(Khaya senegalensis)、牙刷樹(Salvadora persica)、葫蘆科(Cucurbitaceae)之藥西瓜(Citrullus colocynthis)等之萃取物。許多此類萃取物揭示於美國專利案Nos.6,264,926與7,083,779、及美國專利申請公開案Nos.2009/0087501與2007/0116652。
本發明之口腔保健組成物可採取適用於施敷於口腔表面之任何形式。於各種說明用具體實例中,組成物可為適用於沖洗、清洗或噴灑之液體溶液;例如粉劑、牙膏或牙科用凝膠之
潔牙劑;牙周凝膠;適用於塗在牙齒表面之液體(例如,液體潔白劑);口香糖;可溶、部分可溶或不可溶之膜片或長條或貼片(例如,潔白牙貼);珠粒(例如,封裝於明膠中之組成物)、粉片;拭巾或紙巾;植入物;漱口水、泡沬劑、牙線等。除了上文列舉者外,組成物可含有活性及/或載體組成。
於特定具體實例中,係使組成物適用於施敷在小家畜(例如貓或狗)口腔表面。此類組成物通常可被動物食用或咀嚼,及可採取例如貓食或狗食、零嘴或玩具之形式。
本文中將組成分類為活性劑或載體組成,乃為了清楚和方便,不應將特定組成根據其於本文中之分類推斷其於組成物中之必然功能。再者,特定組成可具有多種功能,因此於本文中揭示一組成為一功能組群之實例並未排除其亦可為另一功能組群實例之可能性。
於一具體實例中,係提供至少含有薑萃取物、口腔可接受之載體、及除了薑萃取物以外之天然萃取物之牙膏組成物。薑屬於薑科(Zingeberaceae),種植於世界各地,尤其是印度、中國、墨西哥等地;它是種植於印度之主要香料作物,呈新鮮及乾燥香料銷售;其為生長於一年中所有季節之多年生小草本植物。印度薑以其風味、質地與口感聞名。薑不只是香料,它被視為係味道製造劑、藥物、開胃劑及調味劑。薑產品可為各種形式如油、油性樹脂、生薑鹽水、泡菜、糖果、糖漿等。漂白及未漂白之粉末形式之薑亦可於市場中獲得。印度於薑生產及出口上具顯著地位。於世界市場上,印度薑俗稱科欽(Cochin)薑與喀利坷(Calicut)薑。主要買主為中東、美國、英國及荷蘭。薑一般用於腹脹、咳嗽、
嘔吐、腹瀉、風濕等。
種植薑主要為了其根部或地下莖。薑之最接近之化學組成已被研究且證實含有大約1-4%揮發油,為薑之醫學活性成分(2009/0131364);揮發油被認為是由畢沙波林、桉油酚、水芹烯、檸檬醛、龍腦、香茅醛、香葉醛、芳樟醇、檸檬烯、薑醇、薑鹼、莰烯等組成。存在薑中之油性樹脂主要為薑油與薑烯酚,雖然萃取物尚包括去氫薑二酮。薑之溶劑萃取物中檢測出之酚類主要為薑油與薑酮。除了例如維生素B6、維生素C、鈣、鎂、磷、鉀與亞麻油酸等其他成分外,生薑蛋白酶,一種蛋白水解酵素,亦存在薑中。薑之刺激性與氣味已鑑定出主要由於薑油,其分別含有油性樹脂之醇基、揮發油;文獻上已證實,如此使薑成為自由基清除劑及具抗突變及消炎性質。
薑萃取物可利用任何各種已知萃取方法製得。萃取物被認為含有任何一或多種下述化合物,其本身,或組合萃取物中發現之其他化合物,可於具體實例中使用。薑萃取物可包括畢沙波林、桉油酚、水芹烯、檸檬醛、龍腦、香茅醛、香葉醛、芳樟醇、檸檬烯、薑醇、薑鹼、莰烯、薑油、薑烯酚、薑酮、生薑蛋白酶、維生素B6、維生素C、鈣、鎂、磷、鉀、亞麻油酸、黏膠質性多醣類(鼠李糖、阿拉伯糖、木糖、甘露糖、半乳糖、葡萄糖等)、沒食子酸、單寧酸、龍膽酸、原兒茶酸、香草酸、咖啡酸、丁香酸、肉桂酸、及其混合物。
於另一具體實例中,本發明提供用於抑制對象動物口腔之細菌生長及/或發炎之方法。該方法較佳為治療口腔軟組織之方法,其包括投與包含薑萃取物、口腔可接受之載體、及除了
薑萃取物以外之天然萃取物之組成物至口腔軟組織中。
於另一具體實例中,本發明提供含有水、調味劑、及至少一種含氫成分例如乙醇、甘油、與山梨糖醇連同薑萃取物、及至少一種除了薑萃取物以外之天然萃取物之漱口水或漱口藥。於另一具體實例中,本發明提供除了薑萃取物以外,含有口香糖基劑與調味劑、及除了薑萃取物以外之天然萃取物之口香糖。於又另一具體實例中,係提供除了薑萃取物以外,含有膜形成聚合物與視需要之調味劑、及除了薑萃取物以外之天然萃取物之爽口片。
於一態樣中,組成物包含除了薑萃取物以外之天然萃取物。只要能提高薑萃取物之抗細菌、消炎、與抗氧化劑作用,任何適當萃取物均可使用。適當萃取物包括,例如,牛膝草、木蘭、蔓越橘、迷迭香、山茶、桑色素、肉荳蔻、洋棗、石榴、山竹、橙枳、印度苦楝、阿拉伯膠、烏龍茶、胡桃、竹葉花椒、牛油果、黃葵、阿育吠陀印度草藥、長楝樹、非洲楝、牙刷樹、葫蘆科之藥西瓜等之萃取物。
特佳之萃取物包括牛膝草、木蘭、蔓越橘、迷迭香、山茶、桑色素、肉荳蔻、洋棗、石榴、山竹、橙枳、印度苦楝、阿拉伯膠、烏龍茶、胡桃、竹葉花椒、牛油果、黃葵、阿育吠陀印度草藥、長楝樹、非洲楝、牙刷樹、葫蘆科之藥西瓜、兒茶(Acacia catechu)、阿拉伯金合歡(Acacia nilotica)、紫莖牛膝、印度苦楝、苞片馬兜鈴、樟樹(Cinnamomum camphora)、錫蘭肉桂(Cinnamomum verum)、薑黃(Curcuma longa)、藍桉(Eucalyptus globulus)、囊葉榕、胡桃、長葉馬府油樹(Madhuca longifolia)、牛油果、九層塔(Ocimum sanctum)、烏龍茶、荖藤葉、蓽撥(Piper longum)、胡椒(Piper nigrum)、西南委陵菜(Potentilla fulgens)、丁香(Syzygium aromaticum)、六神草(Spilanthes calva)、蔓越莓(Vaccinium macrocarpon)、竹葉花椒(Zanthoxylum armatum)之萃取物,及其混合物。
附加之萃取物可為選自下述屬別之一或多種植物:牛至(Origanum)屬、百里香(Thymus)屬、薰衣草(Lavandula)屬、鼠尾草(Salvia)屬、香蜂草(Melissa)屬、小茴香(Cuminum)屬、歐芹(Petroselinum)屬、金盞花(Calendula)屬、萬壽菊(Tagetes)屬、乳香(Boswellia)屬、接骨木(Sambucus)屬、香脂蘇木(Copaifera)屬、鬱金(Curcuma)屬、蔥(Allium)屬、康福利草(Symphytum)屬、石榴(Punica)屬、甘藍椰子(Euterpe)屬、槐(Sophora)屬、大黃(Rheum)屬、蕎麥(Fagopyrum)屬、山茶屬、黃連(Coptis)屬、白毛茛(Hydrastis)屬、十大功勞(Mahonia)屬、黃蘗(Phellodendron)屬、小蘗(Berberis)屬、黃根草(Xanthorhiza)屬、忍冬(Lonicera)屬、苔莓(Vaccinium)屬、樟樹(Cinnamomum)屬、葡萄(Vitis)屬、欖仁樹(Terminalia)屬、松樹(Pinus)屬、合歡(Albizia)屬、楝樹(Melia)屬、Salvadora屬、泡林藤(Paullinia)屬、胡椒(Piper)屬、丁香(Syzygium)屬、沒藥樹(Commiphora)屬、胡桃(Juglans)屬、黃芩(Scutellaria)屬、與木蘭(Magnolia)屬。
更詳言之,本文所述組成物中所用附加之天然萃取物可自下述品種植物萃取:野薄荷(Origanum vulgare)、柳薄荷(Origanum onites)、馬鬱蘭花(Origanum majorana)、希臘牛至(Origanum heracleoticum)、木立百里香(Thymus vulgaris L)、檸檬百里香(Thymus citriodorus)、寬葉百里香(Thymus pulegioides)、荷
巴百里香(Thymus x herba-barona)、野百里香(Thymus serpyllum)、薰衣草(Lavandula angustifolia/officinalis)、西班牙薰衣草(Lavandula stoechas)、齒葉薰衣草(Lavandula dentate)、醒目薰衣草(Lavandula x intermedia)、蕨葉薰衣草(Lavandula multifida)、鼠尾草(Salvia officinalis)、迷幻鼠尾草(Salvia divinorum)、白鼠尾草(Salvia apiana)、香蜂草(Melissa officinalis)、小茴香(Cuminum cyminum)、荷蘭芹(Petroselinum crispum)、野金盞花(Calendula arvensis)、歐洲金盞花(Calendula maderensis)、金盞花(Calendula officinalis)、萬壽菊(Tagetes erecta)、印加孔雀草(Tagetes minuta)、孔雀草(Tagetes patula)、乳香(Boswellia sacra)、阿曼乳香(Boswellia frereana)、返魂香(Boswellia serrata)、乳香樹(Boswellia papyrifera)、西洋接骨木(Sambucus nigra)、黑莓接骨木(Sambucus melanocarpa)、金葉接骨木(Sambucus racemosa)、藍氏香脂蘇木(Copaifera langsdorfii)、薑黃、大蒜(Allium sativum)、康福利草(Symphytum officinale)、石榴(Punica granatum)、巴西紫莓(Euterpe oleracea)、苦參(Sophora flavescens)、波葉大黃(Rheum rhabarbarum)、圓葉大黃(Rheum rhaponticum)、蕎麥(Fagopyrum esculentum)、中國茶(Camellia sinensis)、雲連(Coptis teeta)、金印草(Hydrastis canadensis)、尖頭葉十大功勞(Mahonia aquifolium)、闊葉黃蘗(Phellodendron amurense)、刺小蘗(Berberis vulgaris)、黃根草(Xanthorhiza simplicissima)、忍冬(Lonicera ceprifoliu)、蔓越莓、錫蘭樟(Cinnamomum zeylanicum Nees)、錫蘭肉桂、葡萄(Vitis vinifera)、毗黎勒(Terminalia bellerica)、海岸松(Pinus pinaster)、大葉合歡(Albizia lebbek)、印度苦楝(Melia azadirachta)、牙刷樹
(Salvadora persica)、瓜拿納泡林藤(Paullinia cupana)、荖藤(Piper betle)、丁香、沒藥(Commiphora myrrha)、胡桃、中國黃芩(Scutellaria baicalensis)、與厚朴(Magnolia officinalis)。
與薑萃取物一起使用之附加天然萃取物亦可選自一或多種下述天然萃取物:牛膝[紫莖牛膝(Achyranthes aspera)、蘆薈[包括蘆薈(Aloe)屬之翠葉蘆薈(A.barbadensis)、好望角蘆薈(A.ferox)與吉拉索蘆薈(A.vera)]、大茴香[茴芹(Pimpinella anisum)]、馬兜鈴[苞片馬兜鈴(Aristolochia bracteolate)]、山金車[金車菊(Arnica)屬,包括輝洋菊(A.fulgens)]、榕樹[囊葉榕(Ficus bengalensis)]、牛油果、羅勒[甜羅勒(Ocimum basilicum)與希臘羅勒(O.minimum)]、荖藤、胡椒、樟腦(樟樹)、兒茶、白屈菜(Cheliaonium)屬、香菊(Matricaria chamomilla)、藏青果(Terminalia chebula)、中國黃芩、Cinnamomum lourerii與C.zeylandicum二肉桂品種、柑橘屬植物[柑橘(Citrus)屬,包括萊姆(C.aurantifolia)、酸橙(C.aurantium)、檸檬(C.limonum)與甜橙(C.sinensis)]、丁香、蒔蘿(Anethum)屬包括小茴香(A.graveolens)與印度時蘿(A.sowa)、淡紫馬蘭菊(Echinacea pallida)、桉樹屬植物(藍桉)、茴香(Foeniculum vulgare)、梔子花(Gardenia jasminoides)、葡萄(Vitis vinifera)、蛇麻(Humulus lupulus)、魚腥草(Houttuynia cordata)、印第安桑樹[諾麗果(Morinda citrifolia)]、杜松(Juniperus communis)、檸檬草[香茅(Cymbopogon)屬,包括香茅草(C.citratus)與檸檬香茅(C.flexuosus)]、甘草(Glycyrrhiza)屬之甘草(G.glabra)與烏拉爾甘草(G.uralensis)、長番椒(蓽撥)、紫荊木屬植物(長葉馬府油樹)、木蘭(厚朴)、金盞花、乳香(Pistacia lentiscus)、黃香草木樨(Melilotus officinalis)、西洋蓍草(Achillea millefolium)、沒藥[沒藥樹屬,包括阿比尼西亞沒藥(C.abyssinica)與末藥(C.molmol)]、印度苦楝、酸橙、肉荳蔻、沒食子櫟(Quercus infectoria)、荷蘭芹(Petroselinum sativum)、牙刷樹、薄荷(Mentha piperita)、松樹[松樹屬,包括大王松(P.palustris)與歐洲赤松(P.sylvestris)]、石榴、多刺阿拉伯膠(阿拉伯膠樹皮)(阿拉伯金合歡)、豆科灌木植物[拉坦尼(Krameria)屬,包括阿根廷拉坦尼(K.argentea)與孔裂藥豆(K.triandra)]、迷迭香(Rosmarinus officinalis)、番紅花(Crocus sativus)、鼠尾草[鼠尾草屬,包括山艾(S.lavendulaefolia)、鼠尾草與三裂鼠尾草(S.triloba)]、檀香[檀香(Santalum)屬,包括東印度白檀香(S.album)與澳洲檀香(S.spicatum)]、綠薄荷(Mentha spicata)、六神草、八角茴香(Illicium verum)、茶(包括綠茶與烏龍茶)、中國茶、百里香[百里香屬,包括野百里香與百里香(Thymus vulgaris)]、竹葉花椒、九層塔、薑黃、須松蘿(Usnea barbata)、西南委陵菜、胡桃、矮冬青(Gaultheria procumbens)、及其混合物。
如本文所詳述,附加之天然萃取物可能源於或基於自植物單離之化合物或萃取物。下述植物各提供用於口腔用組成物中之一或多種活性成分,以得到一或多種口腔保健好處。舉例而言,得自迷迭香(Romains officinalis)之萃取物具有抗細菌及消炎作用。迷迭香萃取物含有各種有機及無機物質,包括類黃酮類、三萜酸與酚酸類。有用的有機化合物之非限制實例包括1,8-桉油酚、樟腦、α-蒎烯、鼠尾草酸、迷迭香酸、熊果酸、鼠尾草醇、與齊墩果酸。本文中有關各種萃取物所含活性化合物之討論包括一般相信於口腔用組成物中具效力之彼等化合物;然而,此類化合物之
列舉並無排他性及於若干情形下尚有待鑑定或充分確認,然而,實驗觀察證明所預期之效力。再者,於各種態樣中,包括其中所含所有化合物之整個萃取物提供最有效之植物性活性成分。於口腔用組成物中使用之迷迭香萃取物詳述於頒給Trivedi等並讓渡給Colgate-Palmolive之美國專利公開案2006/0134025。迷迭香植物樹葉之萃取物呈迷迭香萃取物,舉例而言,由Sabinsa Corporation(Piscataway,N.J.,USA)銷售。於各種植物性萃取物中發現之此類化合物可從萃取物中單離,呈植物性活性成分單獨使用。舉例而言,可單獨單離已被發現對引起蛀牙、牙齦炎、與口臭之口腔細菌具效力之鼠尾草酸,於口腔用組成物中使用。
根據本發明教示有用之其他萃取物包含薄荷(Lamiaceae)科植物之任何適當部分,包括分類為下述屬之植物:牛至屬、百里香屬、薰衣草屬、鼠尾草屬、分藥花(Perovskia)屬、糙蘇(Phlomis)屬、或香蜂草屬。舉例而言,適當萃取物包括得自野薄荷(Origanum vulgare L.)(俗稱"牛膝草"、"野牛膝草"、或"野馬鬱蘭")者,包括其亞種(Origanum vulgare ssp.)、柳薄荷(俗稱"義大利牛膝草"或"盆栽馬鬱蘭")、馬鬱蘭花(俗稱"馬鬱蘭"或"甜馬鬱蘭")與希臘牛至。野薄荷亞種包括O.vulgare ssp.vulgare、O.vulgare ssp.viride、與O.vulgare ssp.hirtum(俗稱"希臘牛膝草"或"野牛膝草")。本文所用之“牛膝草”一詞涵蓋牛至屬之所有適當品種與亞種。牛膝草被認為含有30種以上活性化合物,包括香草芹酚(carvarcrol)、瑞香草酚、與迷迭香酸。
亦屬於薄荷科之百里香屬包含超過三百個品種與亞種;適當萃取物包括自下述植物單離者:木立百里香、檸檬百里
香、寬葉百里香、荷巴百里香、與野百里香。本文所用之“百里香”一詞涵蓋百里香屬之所有適當品種與亞種,及由其衍生之萃取物,其中被認為含有香草芹酚與瑞香草酚活性化合物。
其他適當萃取物包括得自薰衣草屬者,其包含超過30個品種。適當薰衣草品種包括薰衣草(為先前已知之L.Officinalis L.)、西班牙薰衣草、齒葉薰衣草、醒目薰衣草、與蕨葉薰衣草(Lavandula multifida)。薰衣草萃取物含有活性化合物例如乙酸芳樟酯與芳樟醇等。本文所用之“鼠尾草”一詞通常包括屬於薄荷科三個屬之植物;亦即鼠尾草屬、分藥花屬、糙蘇屬。於特定態樣中,有用之植物包括一般鼠尾草、迷幻鼠尾草、與白鼠尾草。得自鼠尾草之萃取物具有例如抗生、抗真菌、及收歛劑等作用。另一適當萃取物係衍生自檸檬香植物(香蜂草),其具有抗細菌及抗病毒性質。
可用於根據本發明具體實例之進一步萃取物亦包括衍生自香芹(Apiaceae)科之植物,包括小茴香屬與歐芹屬。小茴香含有多種活性化合物,包括茴香醛與吡類。荷蘭芹含有洋芹腦、呋喃香豆素、與补骨脂化合物。小茴香及荷蘭芹萃取物具有有利之抗氧化劑活性,以及其他有利作用。
金盞花屬與萬壽菊屬,俗稱"金盞花",均屬於菊(Asteraceae)科。金盞花屬包含許多品種與亞種,包括野金盞花、歐洲金盞花、與金盞花。金盞花屬萃取物含有各種活性化合物,包括金盞酸。萬壽菊屬包含超過六十個品種與亞種,包括萬壽菊、印加孔雀草、孔雀草等。金盞花屬與萬壽菊屬之萃取物均具有抗氧化劑與消炎活性,對引起蛀牙、牙齦炎、與口臭之口腔細菌均
具效力。
乳香屬樹木產生具有消炎性質之萃取物,包括乳香酸化合物。舉例而言,乳香、阿曼乳香、返魂香、與乳香樹及其亞種產生適當之萃取物。自乳香屬植物單離之有用活性化合物為乙醯基酮基-β-乳香酸(AKBBA),例如,3-乙醯基-11-酮基-β-乳香酸,其展現抗細菌、消炎及抗氧化劑等活性。呈BOSWELLIN® CG市售可得之印度乳香萃取物含有β-乳香酸與有機酸混合物,係由Sabinsa Corp.銷售。
接骨木屬包含超過三十個品種與亞種,通常稱為接骨木。各種接骨木品種均適當,包括例如西洋接骨木(常見之接骨木)、黑莓接骨木、金葉接骨木(紅莓接骨木)等。已發現接骨木萃取物具有抗氧化劑活性,並進一步於口腔用組成物中提供一或多種下述好處:抗細菌、抗氧化劑、膠原酶抑制作用、去乙醯化酶(sirtuins)活化作用、及消炎性質。
藍氏香脂蘇木(古巴香脂)萃取物如薑黃一樣有用,彼等含有薑黃素、去甲氧基薑黃素、雙-去甲氧基薑黃素、與四氫類薑黃素等化合物。附加之適當萃取物包括自大蒜(Allium sativum)或蔥(Allium)屬之其他植物單離者。大蒜萃取物含有蒜素、蒜胺酸、大蒜烯、與其他類黃酮類,可提供抗氧化劑及/或抗微生物等好處。得自康福利草屬之康福利草或其他植物之萃取物為有用之抗氧化劑、消炎、及/或抗菌劑;同樣地為含有各種抗氧化劑多酚類例如可水解之石榴單寧酸之石榴萃取物;含有白藜蘆醇、花青素類、及各種其他類黃酮類與似類黃酮化合物,例如葒草素、葒草苷、塔西福林(tasifolin)、去氧六碳糖、異牡荊素、金雀花素之巴西紫
莓;含有具生物活性之類黃酮苦參酮之具有消炎及抗細菌功能之苦參萃取物。上述各萃取物展現一或多種抗氧化劑、消炎、抗病毒、及/或抗細菌性質。苦參酮之代表性結構式為:
於本揭示內容之特定態樣中,口腔用組成物視需要含有衍生自薑黃之市售可得萃取物(可自Sabinsa Corp.購得,商品名為SABIWHITE®),其中包含被認為具下述代表性結構式之四氫類薑黃素:
多種植物萃取物含有活性化合物芸香苷(槲黃素-3-芸香糖苷),芸香苷為抗氧化劑類黃酮糖苷(含有黃酮醇槲黃素與二醣類芸香糖),出現於蓼(Polygonaceae)科之多種植物,包括大黃屬之波葉大黃與圓葉大黃及蕎麥(Fagopyrum esculentum Moench)植物;其代表性結構式被認為如下所示:
芸香苷被認為可清除超氧化物自由基、螯合金屬離子、調控嗜中性細胞爆增、抑制脂質過氧化、維持生物抗氧化劑還原型麩胱甘肽,並涉及產生活性氧分子之芬同反應(fenton reactions)。因此,芸香苷具抗氧化劑、消炎、抗致癌物、抗血栓形成、保護細胞及保護血管等活性,均對口腔用組成物有利。再者,芸香苷增加口腔用組成物之抗牙菌斑及抗氧化劑活性。
抗細菌、抗氧化劑、及/或消炎天然萃取物之非限制實例包括自綠茶或烏龍茶、肉桂、金線草、蔓越橘及其他杜鵑花(Ericaceae)科植物、忍冬、葡萄籽、櫻桃李、迷迭香、東印度胡桃、印楝、珠子草(niruri)、與松樹皮單離者。
綠茶與烏龍茶係自中國茶(Camellia sinensis)單離;可使用其任何變種、形式、或亞種,彼等可選自其任何亞種分類群,其適當實例為:普洱茶(C.sinensis var.assamica),包括,例如,早先之阿薩姆茶(C.assamica)與苦茶(kucha)變種;柬埔寨變種(C.sinensis var.cambodiensis),包括,例如,早先之尖萼茶(lasiocalyx)亞種與撢形(Shan)變種;德宏茶變種(C.sinensis var. dehungensis);白毛茶變種(C.sinensis var.pubilimba);及中國茶原變種(C.sinensis var.sinensis),包括,例如,早先之武夷(bohea)變種、大葉(macrophylla)變種、parvifolia變種、與香花茶(waldenae)變種。一般認為中國茶萃取物之活性成分為多酚兒茶素類包括兒茶素、表兒茶素、表沒食子兒茶素、表兒茶素沒食子酸酯、沒食子兒茶素與表沒食子兒茶素。口腔用組成物中使用之未氧化山茶屬(例如,綠茶)之萃取物見述於頒給Worrell之美國專利公開案No.2006/0141073,氧化之山茶屬(例如,烏龍茶)之萃取物見述於頒給Boyd等之美國專利公開案No.2006/0141039,此二專利公告案均讓渡給Colgate-Palmolive。適當山茶屬萃取物之實例為可自Sabinsa Corp.購得之"Green Tea Extract(綠茶萃取物)CG",產品編號MS-0726-01。
金線草萃取物可自下述一或多種植物獲得:番荔枝(Annonaceae)科、小檗(Berberidaceae)科、防己(Menispermaceae)科、罌粟(Papaveraceae)科、毛茛(Ranunculaceae)科、芸香(Rutaceae)科、薑(Zingiberaceae)科、小檗(Nadina)科、小檗(Mahonia)科、與唐松草(Thalictrum)屬。舉例而言,具有口腔保健組成物之所需優點之金線草萃取物為雲連。金線草萃取物之活性化合物一般相信是小檗鹼(一種消炎、抗微生物化合物)。白毛茛(Goldenseal)屬、金印草,屬於毛茛科,其一活性成分被認為是小檗鹼,以及白毛茛鹼生物鹼類。具有小檗鹼為活性化合物之其他萃取物包括尖頭葉十大功勞(奧勒岡葡萄)、闊葉黃蘗(伏牛花)、刺小蘗、與黃根草(黃根)。
忍冬(Lonicera ceprifolium)萃取物可自忍冬植物之花
獲得。忍冬萃取物中之活性多酚物質被認為是綠原酸及/或木犀草素類黃酮類。杜鵑花科植物泛指超過100個屬及4,000個相關品種,例如見述於頒給Sanker等之美國專利案No.5,980,869者。於特定具體實例中,得自苔莓屬植物(例如蔓越莓)之萃取物為有用之抗細菌天然萃取物。
錫蘭樟或錫蘭肉桂被認為含有包括肉桂醛、丁香酚、肉桂酸乙酯、β-丁香烴、芳樟醇、與甲基蒟酚等多種活性化合物。肉桂萃取物展現抗氧化劑及抗細菌活性。葡萄籽或葡萄皮萃取物係自葡萄植株單離,其中含有各種多酚類,包括白藜蘆醇及抗氧化劑原花青素類。櫻桃李較佳為自毗黎勒水果萃取。松樹皮萃取物較佳為自海岸松之皮層(樹皮)萃取,其中含有碧蘿芷(pycnogenol)並展現抗細菌、消炎、抗氧化劑及抗老化等活性。印楝或苦楝植物(印度苦楝)皮層之萃取物為已知之抗細菌成分。珠子草或苦味葉下珠(Phyllanthus niruri)萃取物亦為已知之抗細菌萃取物。牙刷樹萃取物於口腔保健組成物中提供有效之抗細菌作用。於特定態樣中,附加之天然萃取物可自瓜拿納泡林藤單離,其萃取物含有咖啡因、兒茶素、可可鹼、茶鹼及其他生物鹼。
荖藤萃取物,尤其是衍生自荖藤樹葉之萃取物,被認為含有例如甲氧蒟酚、蒟酚、香艾菊腦、丁香酚、甲基丁香酚、與羥基兒茶酚等活性化合物。丁香萃取物具有防腐及麻醉性質及含有例如丁香酚、β-丁香醇、香草醛、山植酸、柳酸甲酯、單寧類、類黃烷類[包括丁香寧、番鬱金黃素、鼠李素、與丁香寧素(eugentitin)]、三萜類(例如齊墩果酸、豆固醇與菜油固醇)等化合物,及各種倍半萜類。沒藥同樣地為可用於口腔用組成物以提供抗菌
及消炎等好處。另一適當者為胡桃屬植物,包括胡桃(Juglans regia)(波斯胡桃或普通胡桃樹),其萃取物具有消炎及抗氧化劑性質。同樣地,東印度胡桃(大葉合歡)樹葉適於作為萃取物用。
於特定具體實例中,本文所述組成物之附加天然萃取物含有至少一種閒置B環(free-B環)之類黃酮。類黃酮類係包括例如黃酮類、黃烷類、黃酮醇類、二氫黃酮醇類、黃素酮類等化合物類別及其衍生物之一組化合物。用於口腔用組成物之閒置B環類黃酮活性成分見述於頒給Xu等並讓渡給Colgate-Palmolive之美國專利公開案No.2006/0140881。
於各種具體實例中,附加天然萃取物可含有閒置B環類黃酮,其係指通常含有2,3-雙鍵及/或4-酮基而於芳族B環上無任何取代基之類黃酮化合物。用於口腔用組成物之此等活性成分見述於頒給Xu等並讓渡給Colgate-Palmolive之美國專利公開案No.2006/0140881。閒置B環類黃酮類可自薄荷科植物單離,尤其是屬於黃芩(Scutellarioideae)亞科者。舉例而言,中國黃芩品種含有大量閒置B環類黃酮類,包括黃芩素、黃芩苷、漢黃芩素、與黃芩糖苷(baicalenoside)。閒置B環類黃酮具有抗氧化劑及消炎性質,並抑制環加氧酶酵素COX-2之一般活性。於特定態樣中,附加之天然萃取物可視需要包含黃芩苷、5,6-二羥黃酮-7-O-葡萄糖苷、與黃芩素、5,6,7-三羥黃酮。於各種具體實例中,本揭示內容口腔用組成物之附加天然萃取物可包含黃芩苷、黃芩素、或其混合物。
木蘭(Magnoliaceae)科植物,例如厚朴(木蘭),含有包括厚朴酚、異厚朴酚、四氫厚朴酚、與四氫異厚朴酚等活性化合物,彼等已顯示具對抗各種口腔細菌之殺細菌性質。於各種態
樣中,厚朴酚及/或異厚朴酚為有用之抗細菌植物性活性成分。得自木蘭萃取物的活性化合物之用途見述於美國專利公開案Nos.2006/0134024(頒給Trivedi等)與2006/0127329(頒給Xu等),此二專利公開案均讓渡給Colgate-Palmolive。
具已知抗菌、抗氧化劑、及/或消炎劑之其他適當天然萃取物為International Cosmetic Ingredient Dictionary and Handbook,Tenth Ed.,2004中所列舉者。
薑萃取物可根據已知方法利用水或醇萃取水或醇溶性成分,或冷凍乾燥薑之根或地下莖予以製備。較佳萃取物可得自薑植物之地下莖。從植物萃取固體或液體物質通常包括使原料與適當溶劑接觸,以移出期望從該原料萃取之物質。當原料為固體時,在與溶劑接觸之前,最好先乾燥及壓碎或磨碎。此類萃取可利用熟習此項技藝者已知之習用方法進行,舉例而言,藉由使用萃取裝置,例如索氏(Soxhlet)裝置,將固體原料保留於保持器中,令溶劑流經原料,使溶劑與原料摻合在一起,然後利用過濾或利用沉澱及傾瀉分離液相與固相或不溶混之二液相。於各種具體實例中,用於口腔保健組成物之植物性活性成分為可再現、品質穩定及具微生物安全性。
製備薑萃取物之一方法包括以萃取溶劑例如甲醇、乙醇、異丙醇、丁醇、二甲苯、苯、或甲苯萃取植物原料,及從該萃取溶劑濃縮及使粗產物結晶化。此產物雖可作為萃取物用,惟附加之程序可用於純化特定經萃取之成分。舉例而言,可使粗產物溶於二醇及視需要之上述之一溶劑中,然後使溶解之粗產物分配於溶劑相與二醇相間。若上述之一溶劑未與二醇一起添加,
則於分配於兩相間之前添加一或多種溶劑;若已與二醇一起添加,則於分配程序之前再添加更多上述之一溶劑。濃縮溶劑相,從濃縮物中使該萃取物再結晶。。
製備薑萃取物之另一方法為熱水萃取法。熱水萃取法之溫度條件與時間條件並未特別限制,可為熱水萃取法之一般條件(例如,製備煎劑之一般條件;於沸點溫度萃取30至60分鐘)。溫度較佳為80℃至100℃,更佳為90℃至95℃,時間較佳為不少於1小時,更佳為不少於2小時,特佳為不少於3小時。此等溫度條件與時間條件下之熱水萃取因可獲得高度有效組成物而被喜用。熱水萃取所用水量並未特別限制,惟通常每1重量份薑為5至20重量份水,較佳為10重量份水。
藉由濃縮所得萃取液,可去除不需要之揮發性成分,且可製得口服投與大量時對消化器官負擔較小之製劑。萃取液較佳為於50℃至90℃,大氣壓力或減壓下,更佳為於50℃至60℃,減壓下,濃縮至固體含量濃度為20重量%至40重量%,較佳為25重量%至35重量%。
再者,藉由添加賦形劑至所得濃縮物及乾燥,可製得穩定之粉末製劑。賦形劑並未特別限制,只要為食品或製藥劑即可,例如澱粉(例如,玉米澱粉、馬鈴薯澱粉、小麥澱粉、米澱粉)、葡萄糖、果糖、山梨糖醇、甘露糖醇、羧甲基纖維素、羧甲基纖維素鈣、乳糖、蔗糖、羥丙基纖維素、碳酸鎂、氧化鎂、磷酸鈣等。每1重量份濃縮物所添加賦形劑之量通常為1重量份至20重量份,較佳為2重量份至10重量份。乾燥較佳為於溫度60℃至70℃進行。
薑萃取物之另一製法係利用乙醇萃取程序。此方法
中,係以1:3之重量對容積比,使乾燥保存之薑植物原料(較佳為根或地下莖)在乙醇中摻合。然後可過濾混合物,殘留物再於新鮮乙醇中混合(若需要,則此步驟可重複3至5次),收集每一次過濾之濾液。接著乾燥收集之濾液以去除溶劑(例如,於45℃旋轉乾燥),然後進行凍乾使萃取物完全乾燥。經乾燥之萃取物於是可作為萃取物用,或再次於乙醇中再組成。
薑萃取物亦可以類似方式,利用索氏熱萃取法(hot soxhalation)製備。舉例而言,可使用溶劑例如石油醚、正己烷、二氯甲烷、氯仿、乙醇、乙酸乙酯、丙酮與甲醇,使薑地下莖粗粉原料於最適溫度進行熱索氏萃取,循環操作至完成萃取。然後過濾植物萃取液,於旋轉式蒸發器或最適溫度之蒸汽浴上濃縮至乾。
薑萃取物亦可以植物之根或地下莖製備:使乾燥地下莖進行蒸汽蒸餾,蒸發濃縮所得蒸餾液,得到粗萃取物(然後如上述進一步處理)。此外,薑萃取物之製取可藉由使用超臨界CO2萃取乾燥地下莖粉末,回收所得超臨界CO2萃取溶液,從萃取溶液中蒸發CO2,製得粗萃取物。
薑萃取物之成分可利用使萃取物於各種移動相中,分別在用於定性及定量估計標記化合物與活性成分之預塗敷TLC板(Merck)、ODS管柱及10% Carbowax 20M 2米)GC管柱(溫度70至220℃)上進行HPTLC(高效能薄層層析法)、HPLC(高效能液相層析法)及氣相層析法(GC)予以測定。萃取物較佳為含有下述一或多種:畢沙波林、桉油酚、水芹烯、檸檬醛、龍腦、香茅醛、香
葉醛、芳樟醇、檸檬烯、薑醇、薑鹼、莰烯、薑油、薑烯酚、薑酮、生薑蛋白酶、維生素B6、維生素C、鈣、鎂、磷、鉀、亞麻油酸、黏膠質性多醣類(鼠李糖、阿拉伯糖、木糖、甘露糖、半乳糖、葡萄糖等)、沒食子酸、單寧酸、龍膽酸、原兒茶酸、香草酸、咖啡酸、丁香酸、肉桂酸、及其混合物、及其混合物。
經回顧本文之說明內容後,製備薑萃取物之其他方法將為熟習此項技藝者所顯見。
選定各種口腔用組成物中諸成分之治療量,以傳送有效量之薑萃取物至施敷口腔用組成物的對象動物之口腔表面。舉例而言,於牙膏及潔牙膠中,本文所述萃取物組合物之適當濃度包括0.01重量%至5重量%,例如0.05至5重量%,特別是0.1至0.3重量%。
至於牙粉,其治療量與牙膏及潔牙膠大約相同,而漱口水及漱口藥則治療量往往較少。舉例而言,漱口水及漱口藥含有0.01至2重量%之萃取物組合物,例如0.01%至0.6%、0.01%至0.2%、及0.01至0.05%。此外,口香糖、塗抹組成物、爽口片等往往以寬廣範圍之萃取物濃度調配。於各種具體實例中,萃取物用量與漱口水中用量相似。
於一態樣中,添加有關各種口腔用組成物上文詳述治療量之萃取物組合物,具有添加從上述量減去由個別成分組成之組成物重量比之治療量之薑萃取物(諸)主要成分之效果;其中薑萃取物(諸)主要成分為例如畢沙波林、桉油酚、水芹烯、檸檬醛、龍腦、香茅醛、香葉醛、芳樟醇、檸檬烯、薑醇、薑鹼、莰烯、薑油、薑烯酚、去氫薑二酮、薑酮、生薑蛋白酶、維生素B6、維
生素C、鈣、鎂、磷、鉀、亞麻油酸、黏膠質性多醣類(鼠李糖、阿拉伯糖、木糖、甘露糖、半乳糖、葡萄糖等)、沒食子酸、單寧酸、龍膽酸、原兒茶酸、香草酸、咖啡酸、丁香酸、肉桂酸、及其混合物與衍生物。因此,於一具體實例中,本發明提供於口腔用組成物中含有治療量為0.01重量%至5重量%之薑油、薑烯酚、去氫薑二酮、黏膠質性多醣、或其混合物之潔牙劑。
於各種具體實例中,係調配含有至少一種潤濕劑、至少一種研磨材料、載體、與有效量萃取物組合物之組成物。於一具體實例中,組成物包含0.01至5重量%之萃取物組合物,較佳為0.1至2重量%之萃取物組合物。於各種較佳具體實例中,除了0.1至2重量%之萃取物組合物外,組成物包含1至70重量%之至少一種潤濕劑、及1至70重量%之至少一種研磨材料。
於各種具體實例中,組成物不包含附加之抗細菌劑,惟其使用係視需要。於使用附加抗細菌劑之情形下,組成物可進一步包含選自包括氯化鯨蠟基吡錠、多酚類、酚化合物、亞錫離子、鋅離子等之組群之抗細菌劑。
本文所述組成物可與視需要之其他組成一起調配,包括惟不限於防齲劑、防牙菌斑或牙垢控制劑、陰離子性羧酸聚合物、黏度修飾劑、界面活性劑、調味劑、色料、信號(味道、顏色、光、氣味及表示組成物之有效或有利用途之其他信號)、口乾治療劑等。
於各種具體實例中,組成物包含口腔可接受之氟離子來源,係作為防齲劑用;可存在一或多個此類來源;適當氟離子來源包括氟化物、磷酸一氟鹽與氟矽酸鹽以及胺氟化物,包括
奧拉氟(olaflur)(N'-十八基三亞甲二胺-N,N,N'-參(2-乙醇)-二氫氟化物)。
關於防齲劑,係視需要存在提供總計100至20,000ppm、200至5,000ppm、或500至2,500ppm氟離子量之一或多種氟離子釋放鹽。舉例而言,當氟化鈉為唯一存在之氟離子釋放鹽時,可呈以重量計0.01%至5%、0.05%至1%或0.1%至0.5%之氟化鈉存在組成物中。亦可使用其他防齲劑,例如精胺酸與精胺酸衍生物(例如,乙基月桂醯基精胺酸(ELAH))。
本文有用之酚化合物(須確定口腔可接受性)之例示包括,惟不限於,經Dewhirst(1980),Prostaglandins 20(2),209-222鑑定具有消炎活性者。抗細菌酚化合物之實例包括4-烯丙基兒茶酚、對羥苯甲酸酯類包括對羥苯甲酸苄酯、對羥苯甲酸丁酯、對羥苯甲酸乙酯、對羥苯甲酸甲酯與對羥苯甲酸丙酯、2-苄苯酚、丁基羥基甲氧苯、丁基羥基甲苯、辣椒素、香芹酚、甲酚、丁香酚、癒創木酚、鹵化雙酚類包括六氯酚與溴氯酚、4-己基間苯二酚、8-羥基喹啉及其鹽、柳酸酯類包括柳酸酯、柳酸甲酯與柳酸苯酯、酚、兒茶酚、柳醯胺苯、與瑞香草酚。彼等酚化合物通常存在上文敘述之一或多種天然萃取物中。
至少一種酚化合物視需要呈0.01至10重量%之總量存在;其於本發明牙膏或凝膠潔牙劑或漱口水中之總濃度可為0.01%至5%,例如0.1%至2%、0.2%至1%或0.25%至0.5%。
其他適當抗細菌劑包括,惟不限於,銅(II)化合物例如氯化銅(II)、氟化銅(II)、硫酸銅(II)與氫氧化銅(II)、鋅離子來源例如乙酸鋅、檸檬酸鋅、葡萄糖酸鋅、甘胺酸鋅、氧化鋅、硫酸
鋅與檸檬酸鋅鈉、酞酸及其鹽例如酞酸一鉀鎂、海克替啶(hexetidine)、奧替尼啶(octenidine)、血根鹼、氯化苄烷銨、度米芬(domiphen)溴、氯化烷基吡錠例如氯化鯨蠟基吡錠(CPC)(包括CPC與鋅及/或醛素之組合物)、氯化十四基氯化吡錠與N-十四基-4-乙基吡錠、碘、磺醯胺類、雙縮胍類例如阿來西啶(alexidine)、氯己啶(chlorhexidine)與二葡萄糖酸氯己啶、N-六氫吡啶基衍生物例如地莫匹醇(delmopinol)與辛哌醇(octapinol)、木蘭萃取物、葡萄籽萃取物、薄荷腦、香葉醇、檸檬醛、桉油醇、抗生素例如安滅菌、胺羥芐青黴素、四環素、去氧土黴素、美諾四環素(minocycline)、甲硝唑、新黴素、卡那黴素(kanamycin)與克林達黴素(clindamycin)等。有用抗細菌劑之進一步例示列表見述於頒給Gaffar等之美國專利案No.5,776,435。如果存在,則彼等附加抗菌劑通常呈以重量計為組成物之0.05%至10%,例如0.1%至3%之抗菌有效總量存在。
於另一具體實例中,組成物包含口腔可接受之防牙菌斑劑;可存在一或多種此類製劑。適當防牙菌斑劑包括惟不限於磷酸鹽與聚磷酸鹽(例如焦磷酸鹽)、多胺基丙磺酸(AMPS)、檸檬酸鋅三水合物、多肽類例如聚天冬胺酸與聚麩胺酸、聚烯烴磺酸酯類、聚烯烴磷酸酯類、二膦酸酯類例如吖環鏈烷-2,2-二膦酸酯類(例如,吖環庚烷-2,2-二膦酸)、N-甲基吖環戊烷-2,3-二膦酸、乙烷-1-羥基-1,1-二膦酸(EHDP)與乙烷-1-胺基-1,1-二膦酸酯、膦醯鏈烷羧酸及任何彼等製劑之鹽,例如其鹼金屬與銨鹽。有用之無機磷酸鹽與聚磷酸鹽之例示包括磷酸二氫鈉、磷酸氫鈉與磷酸鈉、三聚磷酸鈉、四聚磷酸鹽、焦磷酸一鈉、焦磷酸二鈉、焦磷酸三
鈉與焦磷酸四鈉、焦磷酸二氫二鈉、三偏磷酸鈉、六偏磷酸鈉等,其中鈉可視需要以鉀或銨置換。其他有用之防牙菌斑劑包括陰離子性多羧酸聚合物。陰離子性多羧酸聚合物於碳主鏈上含有羧基,包括丙烯酸、甲基丙烯酸、與順丁烯二酸酐之聚合物或共聚物;非限制實例包括聚乙烯甲基醚/順丁烯二酸酐(PVME/MA)共聚物,例如可購自ISP,Wayne,NJ之GantrezTM廠牌。另有一些有用之防牙菌斑劑含有螯合劑包括羥基羧酸例如檸檬酸、反丁烯二酸、蘋果酸、戊二酸與草酸及其鹽、胺基多羧酸例如伸乙二胺四乙酸(EDTA)。一或多種防牙菌斑劑視需要呈以重量計通常為0.01%至50%,例如0.05%至25%或0.1%至15%之防牙菌斑有效總量存在組成物中。
於各種具體實例中,防牙菌斑系由三聚磷酸鈉(STPP)與焦磷酸四鈉(TSPP)之混合物組成。於各種具體實例中,TSPP對STPP之比率在1:2至1:4之範圍內。於較佳具體實例中,第一個防牙菌斑活性成分,TSPP,呈1至2.5%存在,第二個防牙菌斑活性成分,STPP,呈1至10%存在。
於一具體實例中,陰離子性多羧酸聚合物存在0.1%至5%。於另一具體實例中,陰離子性多羧酸聚合物以口腔保健組成物之0.5%至1.5%存在,最佳為1%。於根據本發明之一具體實例中,防牙菌斑系由順丁烯二酸酐與甲基乙烯基醚之共聚物組成,舉例而言,如,上文詳述之Gantrez S-97產品。
於各種具體實例中,TSPP對STPP對合成陰離子性多羧酸鹽之比率在5:10:1至5:20:10(或1:4:2)之範圍內。於一具體實例中,口腔保健組成物之防牙菌斑系由比率1:7:1之TSPP、STPP、
及多羧酸鹽例如順丁烯二酸酐與甲基乙烯基醚之共聚物組成。於非限制性具體實例中,防牙菌斑系主要由TSPP呈0.5%至2.5%存在,STPP呈1%至10%存在,及順丁烯二酸酐與甲基乙烯基醚共聚物呈0.5%至1.5%存在所組成。
於另一具體實例中,組成物包含口腔可接受之亞錫離子來源,可用於,例如,幫助減少牙齦炎、牙菌斑、牙結石、齲齒或人敏感;可存在一或多種此類來源。適當亞錫離子來源包括惟不限於氟化亞錫、其他亞錫鹵化物例如氯化亞錫二水合物、焦磷酸亞錫、有機亞錫羧酸鹽例如甲酸亞錫、乙酸亞錫、葡萄糖酸亞錫、乳酸亞錫、酒石酸亞錫、草酸亞錫、丙二酸亞錫與檸檬酸亞錫、亞錫乙烯果綠定(glyoxide)等。一或多種亞錫離子來源視需要及例如呈以重量計為組成物之0.01%至10%,例如0.1%至7%或1%至5%之總量存在。
於另一具體實例中,組成物包含口腔可接受之鋅離子來源,可用於,例如,作為抗菌劑、防牙菌斑劑或口腔清香劑;可存在一或多種此類來源。適當鋅離子來源包括惟不限於乙酸鋅、檸檬酸鋅、葡萄糖酸鋅、甘胺酸鋅、氧化鋅、硫酸鋅、檸檬酸鋅鈉等。一或多種鋅離子來源視需要及例如呈以重量計為組成物之0.05%至3%,例如0.1%至1%之總量存在。
於另一具體實例中,組成物包含口腔可接受之口腔清香劑。一或多種此類製劑可呈口腔清香有效總量存在。適當口腔清香劑包括惟不限於鋅鹽例如葡萄糖酸鋅、檸檬酸鋅與亞氯酸鋅、α-紫羅酮等。
於另一具體實例中,組成物包含口腔可接受之抗牙
菌斑劑,包括牙菌斑瓦解劑。一或多種此類製劑可呈抗牙菌斑有效總量存在。適當抗牙菌斑劑包括惟不限於亞錫、銅、鎂與鍶鹽、二甲基矽氧烷共聚醇類例如鯨蠟基二甲基矽氧烷共聚醇、木瓜酶、葡萄糖澱粉酶、葡萄糖氧化酶、尿素、乳酸鈣、甘油磷酸鈣、聚丙烯酸鍶類及螯合劑例如檸檬酸與酒石酸及其鹼金屬鹽。
於另一具體實例中,組成物包含除了上述迷迭香成分以外之口腔可接受之消炎劑。一或多種此類製劑可呈消炎有效總量存在。適當消炎劑包括惟不限於類固醇劑例如氟輕松(flucinolone)與氫皮質酮、及非類固醇劑(NSAIDs)例如酮洛酸(ketorolac)、氟比洛芬酯、依布洛芬、奈普生、消炎痛、雙氯芬酸(diclofenac)、依托度酸(etodolac)、消炎痛、舒林酸(sulindac)、托美丁(tolmetin)、酮洛芬、非諾洛芬(fenoprofen)、吡羅昔康(piroxicam)、萘丁美酮(nabumetone)、阿斯匹靈、二氟尼柳(diflunisal)、美洛芬鈉(meclofenamate)、甲芬那酸(mefenamic acid)、羥基保泰松(oxyphenbutazone)與丁二苯吡唑二酮。一或多種消炎劑視需要呈消炎有效量存在組成物中。
本發明組成物視需要含有例如酵素、維生素及抗黏著劑等其他組成。添加酵素例如蛋白酶可防色斑及具其他作用。維生素之非限制實例包括維生素C、維生素E、維生素B5、與葉酸。於各種具體實例中,維生素具抗氧化劑性質。抗黏著劑包括乙基月桂醯基精胺酸(ELAH)、對羥苯甲酸丙酯、無花果酶、矽氧聚合物與衍生物、及群體感應抑制劑。
可視需要包含於本發明組成物中之有用載體為稀釋劑、研磨劑、碳酸氫鹽、pH修飾劑、界面活性劑、泡沬調節劑、
增稠劑、黏度修飾劑、潤濕劑、甜味劑、調味劑與著色劑。可視需要存在一種載體物質,或一種以上相同或不同類別之載體物質。須選擇彼此及與組成物其他組成具相容性之載體。
水為較佳之稀釋劑,於若干組成物(例如漱口藥及潔白液)中,通常附隨醇,例如,乙醇。漱口藥組成物中,水對醇之重量比通常為1:1至20:1,例如3:1至20:1或4:1至10:1。潔白液中,水對醇之重量比可於上述範圍內或低於上述範圍,例如1:10至2:1。
於一具體實例中,本發明組成物包含至少一種研磨劑,可作為例如抛光劑用。可使用口腔可接受之任何研磨劑,惟研磨劑之類型、細度(粒度)與用量須加以選擇,俾使正常使用組成物時,牙齒琺瑯質不會過度磨損。適當研磨劑包括惟不限於,例如呈矽膠、水合矽石或矽石沉澱等形式之矽石、礬土、不溶性磷酸鹽、碳酸鈣、樹脂研磨劑例如尿素-甲醛縮合物等。作為研磨劑用之不溶性磷酸鹽為正磷酸鹽、聚偏磷酸鹽與焦磷酸鹽;其例示實例為正磷酸二鈣二水合物、焦磷酸鈣、β-焦磷酸鈣、三磷酸鈣、聚偏磷酸鈣與不溶性聚偏磷酸鈉。一或多種研磨劑視需要呈以重量計通常為組成物之5%至70%,例如10%至50%或15%至30%之研磨有效總量存在。若存在時,研磨劑之平均粒度通常為0.1至30微米,例如1至20微米或5至15微米。
於進一步之具體實例中,本發明組成物包含至少一種碳酸氫鹽,可用於,例如,由於冒泡及釋放二氧化碳而賦予牙齒及牙齦“乾淨的感覺”。可使用口腔可接受之任何碳酸氫鹽,包括惟不限於鹼金屬碳酸氫鹽例如碳酸氫鈉與碳酸氫鉀、碳酸氫銨
等。一或多種碳酸氫鹽視需要呈以重量計為組成物之0.1%至50%,例如1%至20重量%之總量存在。
於又進一步之具體實例中,本發明組成物包含至少一種pH修飾劑。此類製劑包括降低pH之酸化劑、提高pH之鹼化劑及控制pH於所需範圍內之緩衝劑。舉例而言,可包含選自酸化劑、鹼化劑與緩衝劑之一或多種化合物以提供2至10之pH,或於各種例示具體實例中提供2至8、3至9、4至8、5至7、6至10、7至9等pH。可使用口腔可接受之任何pH修飾劑,包括惟不限於羧酸、磷酸與磺酸及其鹽(例如,檸檬酸一鈉、檸檬酸二鈉、蘋果酸一鈉等)、鹼金屬氫氧化物例如氫氧化鈉、碳酸鹽例如碳酸鈉、碳酸氫鹽、倍半碳酸鹽、硼酸鹽、矽酸鹽、磷酸鹽(例如,磷酸一鈉、磷酸三鈉、焦磷酸鹽等)、咪唑等。一或多種pH修飾劑視需要呈有效維持組成物於口腔可接受之pH範圍內之總量存在。
於又進一步之具體實例中,本發明組成物包含至少一種界面活性劑,可用於,例如,協調組成物之其他成分因而提供增強之穩定性;由於清淨力而幫助清潔牙齒表面;及於攪動時(例如,使用本發明潔牙劑組成物刷牙時)提供泡沬。可使用口腔可接受之任何界面活性劑,其中大部分為陰離子性、非離子性或兩性。適當之陰離子性界面活性劑包括惟不限於C8-20烷基硫酸鹽之水溶性鹽、C8-20脂肪酸之磺酸單甘油酯、肌胺酸鹽、牛磺酸鹽等。彼等之例示實例及其他類別包括月桂基硫酸鈉、椰子單甘油酯磺酸鈉、月桂基肌胺酸鈉、月桂基異乙二磺酸鈉、月桂醇聚醚羧酸鈉與十二基苯磺酸鈉。適當之非離子性界面活性劑包括惟不限於泊洛沙姆類(poloxamers)、聚氧乙烯山梨糖醇酯類、脂肪醇乙氧基化
物、烷基酚乙氧基化物、三級胺氧化物、三級膦氧化物、二烷基亞碸等。適當之兩性界面活性劑包括惟不限於具有陰離子基團例如羧酸根、硫酸根、磺酸根、磷酸根或膦酸根之C8-20脂族二級與三級胺之衍生物;其適當實例為椰油醯胺丙基甜菜鹼。一或多種界面活性劑視需要呈以重量計為組成物之0.01%至10%,例如0.05%至5%或0.1%至2%之總量存在。
於又進一步之具體實例中,本發明組成物包含至少一種泡沬調節劑,可用於,例如,攪動時增加組成物產生的泡沬之量、厚度或穩定性。可使用口腔可接受之任何泡沬調節劑,包括惟不限於聚乙烯乙二醇類(PEGs),亦為所謂聚氧乙烯類。以高分子量PEGs為適當,包括平均分子量為200,000至7,000,000,例如500,000至5,000,000或1,000,000至2,500,000者。一或多種PEGs視需要呈以重量計為組成物之0.1%至10%,例如0.2%至5%或0.25%至2%之總量存在。
於又進一步之具體實例中,本發明組成物包含至少一種增稠劑,可用於,例如,賦予組成物所需堅硬度及/或口感。可使用口腔可接受之任何增稠劑,包括惟不限於卡波姆類(carbomers)(亦為所謂羧基乙烯基聚合物)、鹿角菜苷類(亦為所謂紅藻膠,更特別是-鹿角菜苷)、纖維素聚合物例如羥乙基纖維素、羧甲基纖維素(CMC)及其鹽例如CMC鈉、天然膠例如刺梧桐膠、三仙膠、阿拉伯膠與黃蓍膠、膠態矽酸鋁鎂、膠態矽石等。一或多種增稠劑視需要呈以重量計為組成物之0.01%至15%,例如0.1%至10%或0.2%至5%之總量存在。
於又進一步之具體實例中,本發明組成物包含至少
一種黏度修飾劑,可用於,例如,抑制諸成分之沉澱或分離或促進液體組成物於攪動時之再分散。可使用口腔可接受之任何黏度修飾劑,包括惟不限於礦油、礦脂、黏土及有機改性之黏土、矽石等。一或多種黏度修飾劑視需要呈以重量計為組成物之0.01%至10%,例如0.1%至5%之總量存在。
於又進一步之具體實例中,本發明組成物包含至少一種潤濕劑,可用於,例如,防止牙膏暴露於空氣後之硬化。可使用口腔可接受之任何潤濕劑,包括惟不限於多元醇例如甘油、山梨糖醇、木糖醇或低分子量PEGs。大多數潤濕劑亦具甜味劑之功能。一或多種潤濕劑視需要呈以重量計為組成物之1%至70%,例如1%至50%、2%至25%、或5%至15%之總量存在。
於又進一步之具體實例中,本發明組成物包含至少一種甜味劑,可用於,例如,提高組成物之品味。可使用口腔可接受之任何天然或人工甜味劑,包括惟不限於葡萄糖、蔗糖、麥芽糖、糊精、乾燥之轉化糖、甘露糖、木糖、核糖、果糖、左旋糖、半乳糖、玉米糖漿(包括高果糖玉米糖漿與玉米糖漿固體)、部分水解之澱粉、氫化澱粉水解物、山梨糖醇、甘露糖醇、木糖醇、麥芽糖醇、異麥芽、阿斯巴甜、紐甜(neotame)、糖精及其鹽、二肽系強烈甜味劑、賽克拉美(cyclamate)等。一或多種甜味劑視需要呈強烈取決於所選擇之特定甜味劑,惟以重量計通常為組成物之0.005%至5%之總量存在。
於又進一步之具體實例中,本發明組成物包含至少一種調味劑,可用於,例如,提高組成物之品味。可使用口腔可接受之任何天然或合成調味劑,包括惟不限於香草醛、鼠尾草、
馬鬱蘭、荷蘭芹油、綠薄荷油、肉桂油、矮冬青油(柳酸甲酯)、薄荷油、丁香油、月桂油、大茴香油、桉油、橘皮油、衍生自檸檬、柳橙、萊姆、葡萄柚、杏、香蕉、葡萄、蘋果、草莓、櫻桃、鳯梨等之水果油與香精、豆類與堅果衍生之調味料例如咖啡、可可、可樂、花生、杏仁等、吸附及封裝之調味劑等。亦涵蓋於本文調味劑內者為提供口腔之香味及/或其他感官效果(包括降溫或加溫效果)之組成。此類組成之例示包括薄荷腦、乙酸酯、乳酸酯、樟腦、桉油、桉油醇、茴香腦、丁香酚、桂皮、覆盆子酮、α-紫羅蘭酮、丙烯基乙基癒創木酚、瑞香草酚、芳樟醇、苯甲醛、肉桂醛、N-乙基-對烷-3-羧胺、N,2,3-三甲基-2-異丙基丁醯胺、3-(1-氧基)-丙烷-1,2-二醇、肉桂醛甘油縮醛(CGA)、酮甘油縮醛(MGA)等。一或多種調味劑視需要呈以重量計為組成物之0.01%至5%,例如0.1%至2.5%之總量存在。
於又進一步之具體實例中,本發明組成物包含至少一種著色劑。本文之著色劑包括色料、染料、色素及賦予特定光澤或反射性之製劑例如珠光劑。著色劑具有一些功能,包括例如於牙齒表面提供白色或淺色塗層、於已實際接觸組成物之牙齒表面位置具有指標作用、及/或修飾外觀(特別是組成物之顏色及/或混濁)以加強對消費者之吸引力。可使用口腔可接受之任何著色劑,包括惟不限於滑石、雲母、碳酸鎂、碳酸鈣、矽酸鎂、矽酸鋁鎂、矽石、二氧化鈦、氧化鋅、紅、黃、褐色與黑色氧化鐵、亞鐵氰化銨鐵、錳紫、群青、鈦雲母、氧氯化鉍等。一或多種著色劑視需要呈以重量計為組成物之0.001%至20%,例如0.01%至10%或0.1%至5%之總量存在。
於另一具體實例中,係提供含有水、例如上文詳述之一或多種調味劑、一或多種有機含氫化合物、及如上文詳述之抗細菌有效量之抗細菌組成物之漱口藥或漱口水組成物。於各種具體實例中,漱口藥或漱口水組成物含有0.001%至5重量%之含有熊果酸與鼠尾草酸之植物(例如迷迭香)樹葉之醇萃取物。於較佳具體實例中,組成物含有0.01%至1重量%,例如0.02%至0.5重量%之迷迭香萃取物。該一或多種有機含氫化合物係口腔可接受之有機溶劑,例如,惟不限於,乙醇與甘油。漱口藥及漱口水組成物視需要含有界面活性劑以幫助調味劑與抗細菌組成物之分散。
於各種具體實例中,本發明提供由口香糖基劑與有效量之上文詳述之萃取物組合物組成之口香糖組成物。此外,口香糖調配物通常含有一或多種塑化劑、至少一種甜味劑與至少一種調味劑。
口香糖基劑原料為此項技藝中悉知及包括天然或合成口香糖基劑或其混合物。代表性天然膠或彈性物包括糖膠樹膠、天然橡膠、南洋桐、巴拉塔膠(balata)、馬來橡膠、卡斯皮乳膠(lechi caspi)、索馬乳膠(sorva)、古塔凱乳膠(guttakay)、冠膠、與匹利羅乳膠(perillo)。合成口香糖或彈性物包含丁二烯-苯乙烯共聚物、聚異丁烯and異丁烯-異戊二烯共聚物。口香糖基劑以10至40%及較佳為20至35%之濃度併入口香糖產品中。
於其他具體實例中,口腔用組成物含有由一或多種聚合膜形成劑與有效量之上文詳述之萃取物組合物組之爽口片。該一或多種聚合膜形成劑係選自包括口腔可接受之聚合物例如聚三葡萄糖、纖維素衍生物、及其他可溶性聚合物包括此項技藝中
悉知者之組群。
於各種具體實例中,組成物可有效對抗口腔細菌之組合,舉例而言,如人造口腔抗牙菌斑研究中所示。於各種具體實例中,相較於不含抗細菌組成物之負對照組,觀察到牙菌斑進展顯著減少。
於各種具體實例中,組成物亦顯示抗氧化劑性質,舉例而言,如使用調配之潔牙劑進行LPO-CC測定法所證明,及/或於活體內亦顯示臨床有效性。例如,於較佳具體實例中,本發明組成物於經修飾之牙齦邊緣牙菌斑指數測定中顯示抗牙齦效力。該實驗流程,所謂MGMPI,已經公告。包含有效量迷迭香萃取物之組成物相較於負對照組,顯示明顯之改善。於其他具體實例中,如短期臨床研究所示,本發明組成物亦可有效對抗牙菌斑。
於各種具體實例中,本發明部分係基於發現添加例如於薑萃取物中發現之成分於潔牙劑組成物時,該潔牙劑組成物之消炎作用增強。因此,於各種具體實例中,本發明提供含有萃取物組合物(包括薑萃取物及除了薑以外之天然萃取物)之潔牙劑組成物。
茲參照下述非限制實例更詳細敘述較佳具體實例。
使用下述組成製備牙膏調配物:
相較於不含天然萃取物組合物之習用牙膏調配物,上述牙膏調配物將提供增進之抗細菌及消炎性質。舉例而言,附加之天然萃取物為木蘭、迷迭香、山茶、桑色素、肉荳蔻、烏龍茶、胡桃、竹葉花椒、牛油果、黃葵、阿育吠陀印度草藥、山竹、
長楝樹、非洲楝、牙刷樹、葫蘆科之藥西瓜、兒茶、阿拉伯金合歡、紫莖牛膝、印度苦楝、苞片馬兜鈴、樟樹、錫蘭肉桂、薑黃、藍桉、囊葉榕、胡桃、洋棗、長葉馬府油樹、牛油果、九層塔、烏龍茶、荖藤葉、蓽撥、胡椒、西南委陵菜、丁香、六神草、蔓越莓、竹葉花椒;相較於不含天然萃取物組合物與洋棗之牙膏調配物,該組成物具有增進之抗細菌及消炎效力。
使用下述組成製備漱口藥調配物:
相較於不含天然萃取物組合物之習用漱口藥調配物,上述漱口藥調配物將提供增進之抗細菌及消炎性質。
上文已參照例示實例敍述本發明,惟須瞭解的是,本發明不受限於所揭示之具體實例。研讀本說明書後,熟習此項技藝者可能發生之變更與修飾亦隸屬如隨附申請專利範圍所界定之本發明範圍之內。
Claims (8)
- 一種潔牙劑組成物,其包含:0.01至5重量%之萃取物組合物,其包含薑(Zingiber officinale)萃取物與除了薑萃取物以外之天然萃取物;及口腔可接受之載體,其中除了薑萃取物以外之該天然萃取物係選自由牛膝草(oregano)、木蘭(magnolia)、蔓越橘、迷迭香、山茶(Camellia)屬、桑色素(morin)、肉荳蔻(Myristica fragrans)、洋棗(Zizyphus joazeiro)、石榴(Punica granatum)、山竹(Garcinia mangostana L.)、橙枳(Jabara)、印度苦楝(Azadirachta indica)、阿拉伯膠、烏龍茶、胡桃(Juglans regia)、竹葉花椒(Zanthoxylum alantum)、牛油果(Mimusops elengi)、黃葵(Hibiscus abelmoschus)、阿育吠陀(Ayurvedic)印度草藥、長楝樹(Carapa procera)、非洲楝(Khaya senegalensis)、牙刷樹(Salvadora persica)、葫蘆科(Cucurbitaceae)(藥西瓜(Citrullus colocynthis))、兒茶(Acacia catechu)、阿拉伯金合歡(Acacia nilotica)、紫莖牛膝(Achyrathes aspera)、印度苦楝、苞片馬兜鈴(Aristolochia bracteolate)、樟樹(Cinnamomum camphora)、錫蘭肉桂(Cinnamomum verum)、薑黃(Curcuma longa)、藍桉(Eucalyptus globulus)、囊葉榕(Ficus bengalensis)、胡桃、長葉馬府油樹(Madhuca longifolia)、牛油果(Mimusops elengi)、九層塔(Ocimum sanctum)、烏龍茶、荖藤葉、蓽撥(Piper longum)、胡椒(Piper nigrum)、西南委陵菜(Potentilla fulgens)、丁香(Syzygium aromaticum)、六神草(Spilanthes calva)、蔓越莓(Vaccinium macrocarpon)、竹葉花椒(Zanthoxylum armatum)、及其混合物組成之組群之萃取物之一或多種天然萃取物。
- 根據申請專利範圍第1項之組成物,其包含0.1至2重量%之該萃取物組合物。
- 根據申請專利範圍第1至2項中任一項之組成物,其進一步包含選自:酚化合物、亞錫離子、鋅離子、及其混合物之附加抗細菌劑。
- 根據申請專利範圍第3項之組成物,其中該鋅離子係由選自由乙酸鋅、檸檬酸鋅、葡萄糖酸鋅、甘胺酸鋅、氧化鋅、硫酸鋅、檸檬酸鋅鈉及其混合物組成之組群之一或多種含鋅化合物所提供。
- 根據申請專利範圍第1至2項中任一項之組成物,其中該組成物進一步包含選自由濕劑、研磨劑、防齲劑、防牙菌斑或牙垢控制劑、陰離子性羧酸聚合物、黏度修飾劑、界面活性劑、調味劑、色料及其混合物組成之組群之至少一種附加成分。
- 根據申請專利範圍第1至2項中任一項之組成物,其中該組成物係呈選自由粉劑;牙膏或牙科用凝膠;牙周凝膠;適用於塗在牙齒表面之液體;口香糖;可溶、部分可溶或不可溶膜片或長條;珠粒、粉片;拭巾或紙巾;植入物;漱口水、泡沬劑、與牙線組成之組群之形式之潔牙劑。
- 一種根據申請專利範圍第1至6項中任一項之組成物用於製造供治療口腔軟組織疾病或症狀的口腔保健產品之用 途。
- 根據申請專利範圍第7項之用途,其中該疾病或症狀為口乾症。
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| US26668509P | 2009-12-04 | 2009-12-04 | |
| PCT/US2010/058463 WO2011068811A1 (en) | 2009-12-04 | 2010-12-01 | Oral compositions containing extracts of zingiber officinale and related methods |
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| TW099142014A TW201141502A (en) | 2009-12-04 | 2010-12-03 | Oral compositions containing extracts of zingiber officinale and related methods |
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| JP (1) | JP2013512905A (zh) |
| CN (1) | CN102639189A (zh) |
| AR (1) | AR079305A1 (zh) |
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| TW (2) | TW201345541A (zh) |
| WO (1) | WO2011068811A1 (zh) |
| ZA (1) | ZA201203732B (zh) |
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-
2010
- 2010-12-01 PH PH1/2012/501034A patent/PH12012501034A1/en unknown
- 2010-12-01 CA CA2780345A patent/CA2780345A1/en not_active Abandoned
- 2010-12-01 US US13/513,625 patent/US20120244086A1/en not_active Abandoned
- 2010-12-01 MX MX2012005730A patent/MX2012005730A/es active IP Right Grant
- 2010-12-01 BR BR112012013473A patent/BR112012013473A2/pt not_active IP Right Cessation
- 2010-12-01 JP JP2012542136A patent/JP2013512905A/ja active Pending
- 2010-12-01 CN CN2010800550177A patent/CN102639189A/zh active Pending
- 2010-12-01 AU AU2010326133A patent/AU2010326133B2/en not_active Ceased
- 2010-12-01 MY MYPI2012002208A patent/MY160412A/en unknown
- 2010-12-01 EP EP10787233A patent/EP2506931A1/en not_active Ceased
- 2010-12-01 EP EP13189937.9A patent/EP2712657A1/en not_active Withdrawn
- 2010-12-01 WO PCT/US2010/058463 patent/WO2011068811A1/en not_active Ceased
- 2010-12-01 RU RU2012127767/15A patent/RU2012127767A/ru unknown
- 2010-12-03 TW TW102127709A patent/TW201345541A/zh unknown
- 2010-12-03 TW TW099142014A patent/TW201141502A/zh unknown
- 2010-12-06 AR ARP100104502A patent/AR079305A1/es unknown
-
2012
- 2012-05-15 CO CO12080003A patent/CO6551677A2/es not_active Application Discontinuation
- 2012-05-22 ZA ZA2012/03732A patent/ZA201203732B/en unknown
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| TWI748565B (zh) * | 2020-07-21 | 2021-12-01 | 義美食品股份有限公司 | 用於分離類薑黃素的方法 |
| US11434189B1 (en) | 2021-10-20 | 2022-09-06 | I-Mei Foods Co., Ltd. | Method for isolating curcuminoids from turmeric rhizome |
Also Published As
| Publication number | Publication date |
|---|---|
| RU2012127767A (ru) | 2014-01-20 |
| ZA201203732B (en) | 2014-11-26 |
| EP2712657A1 (en) | 2014-04-02 |
| AU2010326133A1 (en) | 2012-06-07 |
| MX2012005730A (es) | 2012-06-13 |
| EP2506931A1 (en) | 2012-10-10 |
| CN102639189A (zh) | 2012-08-15 |
| CA2780345A1 (en) | 2011-06-09 |
| AU2010326133B2 (en) | 2013-05-30 |
| PH12012501034A1 (en) | 2013-01-14 |
| US20120244086A1 (en) | 2012-09-27 |
| AR079305A1 (es) | 2012-01-18 |
| CO6551677A2 (es) | 2012-10-31 |
| TW201141502A (en) | 2011-12-01 |
| JP2013512905A (ja) | 2013-04-18 |
| BR112012013473A2 (pt) | 2016-05-17 |
| WO2011068811A1 (en) | 2011-06-09 |
| MY160412A (en) | 2017-03-15 |
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