TWI445561B - 含有山竹萃取物及來自山竹之萃取物以外之天然萃取物之萃取物組合物的口腔用組成物 - Google Patents
含有山竹萃取物及來自山竹之萃取物以外之天然萃取物之萃取物組合物的口腔用組成物 Download PDFInfo
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- TWI445561B TWI445561B TW099142013A TW99142013A TWI445561B TW I445561 B TWI445561 B TW I445561B TW 099142013 A TW099142013 A TW 099142013A TW 99142013 A TW99142013 A TW 99142013A TW I445561 B TWI445561 B TW I445561B
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- mangosteen
- zinc
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- 229940079862 sodium lauryl sarcosinate Drugs 0.000 description 1
- 235000019333 sodium laurylsulphate Nutrition 0.000 description 1
- 235000019983 sodium metaphosphate Nutrition 0.000 description 1
- 229940045919 sodium polymetaphosphate Drugs 0.000 description 1
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- DOJOZCIMYABYPO-UHFFFAOYSA-M sodium;3,4-dihydroxy-4-oxobutanoate Chemical compound [Na+].OC(=O)C(O)CC([O-])=O DOJOZCIMYABYPO-UHFFFAOYSA-M 0.000 description 1
- YIVJSMIYMAOVSJ-UHFFFAOYSA-M sodium;hydron;phosphonato phosphate Chemical compound [Na+].OP(O)(=O)OP(O)([O-])=O YIVJSMIYMAOVSJ-UHFFFAOYSA-M 0.000 description 1
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- QJVXKWHHAMZTBY-KSXIZUIISA-N syringin Natural products COc1cc(C=CCO)cc(OC)c1O[C@H]2O[C@@H](CO)[C@H](O)[C@@H](O)[C@@H]2O QJVXKWHHAMZTBY-KSXIZUIISA-N 0.000 description 1
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- 235000010487 tragacanth Nutrition 0.000 description 1
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- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 1
- 230000008733 trauma Effects 0.000 description 1
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 1
- 229940078499 tricalcium phosphate Drugs 0.000 description 1
- 229910000391 tricalcium phosphate Inorganic materials 0.000 description 1
- 235000019731 tricalcium phosphate Nutrition 0.000 description 1
- 229960003500 triclosan Drugs 0.000 description 1
- PLSARIKBYIPYPF-UHFFFAOYSA-H trimagnesium dicitrate Chemical compound [Mg+2].[Mg+2].[Mg+2].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O.[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O PLSARIKBYIPYPF-UHFFFAOYSA-H 0.000 description 1
- MLIKYFGFHUYZAL-UHFFFAOYSA-K trisodium;hydron;phosphonato phosphate Chemical compound [Na+].[Na+].[Na+].OP([O-])(=O)OP([O-])([O-])=O MLIKYFGFHUYZAL-UHFFFAOYSA-K 0.000 description 1
- 150000008130 triterpenoid saponins Chemical class 0.000 description 1
- VSJRDSLPNMGNFG-UHFFFAOYSA-H trizinc;2-hydroxypropane-1,2,3-tricarboxylate;trihydrate Chemical compound O.O.O.[Zn+2].[Zn+2].[Zn+2].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O.[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O VSJRDSLPNMGNFG-UHFFFAOYSA-H 0.000 description 1
- 230000036269 ulceration Effects 0.000 description 1
- 235000013799 ultramarine blue Nutrition 0.000 description 1
- 229940045136 urea Drugs 0.000 description 1
- 235000016788 valerian Nutrition 0.000 description 1
- 230000002666 vasoprotective effect Effects 0.000 description 1
- 239000003981 vehicle Substances 0.000 description 1
- 235000009492 vitamin B5 Nutrition 0.000 description 1
- 239000011675 vitamin B5 Substances 0.000 description 1
- 235000019154 vitamin C Nutrition 0.000 description 1
- 239000011718 vitamin C Substances 0.000 description 1
- 150000003722 vitamin derivatives Chemical class 0.000 description 1
- 239000001717 vitis vinifera seed extract Substances 0.000 description 1
- XLTFNNCXVBYBSX-UHFFFAOYSA-N wogonin Chemical compound COC1=C(O)C=C(O)C(C(C=2)=O)=C1OC=2C1=CC=CC=C1 XLTFNNCXVBYBSX-UHFFFAOYSA-N 0.000 description 1
- 239000002023 wood Substances 0.000 description 1
- 239000008096 xylene Substances 0.000 description 1
- 150000003751 zinc Chemical class 0.000 description 1
- GTQFPPIXGLYKCZ-UHFFFAOYSA-L zinc chlorate Chemical compound [Zn+2].[O-]Cl(=O)=O.[O-]Cl(=O)=O GTQFPPIXGLYKCZ-UHFFFAOYSA-L 0.000 description 1
- 229940085658 zinc citrate trihydrate Drugs 0.000 description 1
- UHVMMEOXYDMDKI-JKYCWFKZSA-L zinc;1-(5-cyanopyridin-2-yl)-3-[(1s,2s)-2-(6-fluoro-2-hydroxy-3-propanoylphenyl)cyclopropyl]urea;diacetate Chemical compound [Zn+2].CC([O-])=O.CC([O-])=O.CCC(=O)C1=CC=C(F)C([C@H]2[C@H](C2)NC(=O)NC=2N=CC(=CC=2)C#N)=C1O UHVMMEOXYDMDKI-JKYCWFKZSA-L 0.000 description 1
- 239000002076 α-tocopherol Substances 0.000 description 1
- 235000004835 α-tocopherol Nutrition 0.000 description 1
Classifications
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- 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
- 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
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- A—HUMAN NECESSITIES
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- 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)
- A61K36/38—Clusiaceae, Hypericaceae or Guttiferae (Hypericum or Mangosteen family), e.g. common St. Johnswort
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- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
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- 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]
- A61K8/9794—Liliopsida [monocotyledons]
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- A—HUMAN NECESSITIES
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- A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
- A61Q11/00—Preparations for care of the teeth, of the oral cavity or of dentures; Dentifrices, e.g. toothpastes; Mouth rinses
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- A—HUMAN NECESSITIES
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- 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
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- Medicinal Preparation (AREA)
Description
本申請案主張2009年12月4日申請之美國專利臨時申請案第61/266,563號之優先權,其併入本文作為參照。
於此所述係包含萃取物組合物之組成物,及其製備與使用之方法。
潔牙劑組成物已被廣泛用於提供口腔健康。呈牙膏、口腔漱劑、口香糖、食用條、粉末、泡沫及其類似物之形式之潔牙劑已以各式各樣之活性物質配製,其提供使用者一些益處。這些益處係抗菌、抗發炎反應及抗氧化性質。這些潔牙劑之性質使它們為有用之治療劑,以防止或治療一些口腔健康症狀,諸如:齲齒、齒齦炎、牙菌斑、牙石、牙周疾病及其類似物。
齒齦炎係齒齦或支撐牙齒之齒槽骨發炎或感染。一般認為齒齦炎係由口腔內細菌(特別是引起牙菌斑形成之細菌)及由細菌形成之副產物毒素所造成。該毒素被認為可引起口腔內口腔組織發炎。與齒齦炎相較,齒根骨膜炎係一逐漸惡化狀態之疾病,其中齒齦發炎且開始由牙齒及帶形萎縮,其最終可能導致骨頭及牙周韌帶之破壞。支撐齒列之結構的細菌感染可包括齒齦炎及齒根骨膜炎,但亦可包括骨頭之感染,例如:由於手術干涉的下顎骨。此外,口腔組織發炎可由手術、局部損傷、外傷、壞死、不當口腔衛生或各種系統性起源所造成。
一般認為受這些疾病及症狀影響之細胞成份包括上皮組織、齒齦纖維母細胞及循環性白血球,其皆有助於對細菌產生之致病因子的宿主反應。與這些口腔感染有關之最常見細菌病原係鏈球菌屬(Streptococci spp.
)(例:轉糖鏈球菌,S. mutans
)、卟啉單胞菌屬(Porphyromonas spp.
)、放線桿菌屬(Actinobacillus spp.
)、非病原性腸桿菌屬(Bacteroides spp.
)及葡萄球菌屬(Staphylococci spp.
)、核粒梭形桿菌(Fusobacterium nucleatum
)、小韋榮球菌(Veillonella parvula
)、納士放線菌(Actinomyces naeslundii
)及牙齦卟啉菌(Porphyromonas gingivalis
)。雖然細菌感染常是許多這些口腔疾病之病因,該疾病之致病機制係由宿主反應所調節。循環性多核嗜中性白血球(PMNs)主要負責感染位置發現之高活動性。典型PMNs及發炎反應之其他細胞媒介物變成超功能性,並釋出毒性化學物質,其部份負責破壞感染病灶周圍之組織。
因此,口腔組織之細菌感染刺激宿主之免疫反應,並經由向上調控可造成重大組織損傷之發炎反應媒介物而減少復原過程。對它們於發炎反應的效應廣泛研究之一類媒介物係花生油酸代謝物,名為前列腺素及白三烯,其經由環加氧酶或脂肪加氧酶酵素途徑產生。這些代謝物牽涉齒齦炎、齒根骨膜炎、骨髓炎及其他發炎疾病之主要媒介物。
於此領域所述有各種組成物,以防止及治療細菌感染造成之口腔發炎。特別是防止衍生自花生油酸途徑之發炎反應媒介物之累積的非類固醇抗發炎反應藥物(NSAIDs)已成功使用於治療罹患牙周疾病及由花生油酸代謝物造成之發炎疾病的患者。實驗及臨床數據顯示吲哚美辛(indomethacin)、氟比洛芬(flurbiprofen)、酮洛芬(ketoprofen)、依布洛芬(ibuprofen)、萘普生(naproxen)及甲氯芬那酸(meclofenamic acid)對齒槽骨流失及牙周疾病模式中前列腺素及白三烯之減少有顯著改善作用。然而,經常使用NSAIDs的一個主要缺點係可能發生胃灼熱、胃潰瘍、胃腸出血及毒性。
其他治療方法包括使用抗微生物療法及抗生素以去除潛在感染。這些療法用以減少刺激物來源(細菌),但緩慢影響對由細菌分泌之毒素的宿主免疫反應。此外,某些抗生素及其他抗微生物療法可能造成口腔黏膜潰瘍、引發脫屑性齒齦炎、變色、長期使用抗生素抗藥性之可能性,以及由於刺激而組織發炎惡化。
精油已被使用於潔牙劑組成物中,主要作為香料。許多精油係植物油,但植物油之組成物與該植物之萃取物極不同。
山竹果(Mangosteen fruit)已被提出為一食品添加物,以宣稱提供健康裨益。美國專利第7,244,463號揭示添加山竹至動物食品中,但未揭示添加山竹萃取物。美國專利第6,730,333號揭示含有山竹(Garcinia mangostana L.
)果實之營養食品組成物,但未揭示添加萃取物。
美國專利第6,800,292號及第6,630,163號揭示使用果實萃取物,諸如:石榴果實萃取物用以治療皮膚病。他們未揭示使用山竹萃取物。
已於文獻中報導山竹(Garcinia mangostana L.
)果實萃取物具有抗氧化劑功效,其有益於治療皮膚症狀,Chang Teng Fan等人“Antioxidative Mechanism of Isolated Components from Methonal Extract of Fruit Hulls ofGarcinia mangostana L.
,”Journal of the Chinese Agricultural Chemical Society
,35
(5):540-551(1997);美國專利申請案公開第2006/0292255號揭示一來自山竹果皮之萃取物,及其作為抗氧化劑以治療皮膚疾病之用途。此公開案揭示此山竹之特殊萃取物包含氧葱酮(xanthone)。同樣地,美國專利申請案公開第2006/0088643號揭示一來自山竹果皮之萃取物,及其於一營養食品飲料之用途。
其他文件揭示在山竹萃取物中存在氧葱酮及其抗氧化優點。特別是兩種氧葱酮,α-及γ-楝子素,與(-)伊皮蓋芹((-)-eepicatechin)、前花青素(procyanidin)A-2及B-2一起被分離出來(Yoshikawa等人,1994,"Antioxidant constituents from the fruit hulls of mangosteen(Garcinia mangostana L.
) originating in Vietnam",Yakugaku Zasshi. 114(2):129-133)。山竹醇(Mangostanol)被報導表現對環狀腺苷單磷酸磷酸二酯酶(cAMP phosphodiesterase)之強抑制作用(Chairungsrilerd及Takeuchi等人,1996,"Mangostanol,a prenyl xanthone fromGarcinia mangostana
"Phytochemistry.
43(5): 1099-1102),以及γ-楝子素較BHA(丁基化羥基甲氧苯,廣泛使用於食品工業之抗氧化劑)及α-生育酚(維生素E)顯現更強抗氧化活性(Yoshikawa等人,1994,as above;及Fan和Su,1997 "Antioxidant mechanism of isolated components from alcohol extract of fruit hulls ofGarcinia mongostana L
".J Chin Agric Chem Soc.
35(5):540-551)。γ-楝子素被報導直接抑制環加氧酶COX 1及COX 2之活性(Nakatani等人,2002,"Inhibition of cyclooxygenase and prostaglandin E2 synthesis by.alpha.-mangostin,a xanthone derivative in mangosteen,in C6 rat glioma cells,”BIOCHEM PHARMACOL. 63:73-79,及Nakatani等人,2004,"γ-Mangostin inhibits inhibitor-K
B kinase activity and decreases lipopolysaccharide-induced cyclooxygenase-2 gene expression in C6
rat glioma cells"Mol Pharmacol.
66(3):667-674.)。γ-楝子素亦被報導抑制去氧核糖核酸拓撲異構酶(Tosa等人,1997,"Inhibitory activity of xanthone derivatives isolated from some Guttiferaeous plants against DNA topoisomerases 1 and II" Chem Pharm Bull. 45(2):418-420.),以及係血清素受體之拮抗物(Chairungsrilerd,Furukawa等人,1996 "Histaminergic and serotonergic receptor-blocking substances from the medicinal plantGarcinia mangostana
,Planta Med.
62(5):471-472;Chairungsrilerd,Furukawa,Ohta等人,1998,"α-Mangostin,a novel type of 5-hydroxytryptamine 2A receptor antagonist Naunyn-Schmiedeberg's,”Arch Pharmacol
. 357:25-31;Chairungsrilerd,Furukawa,Tadao等人,1998,"Effect of α-mangostin through the inhibition of 5-hydroxy-tryptamine 2A receptors in 5-fluoro-.quadrature.-methyltryptamine-induced head-twitch responses of mice,"Br. J. Pharmacol
. 123(5):855-862)。
山竹果汁、果實及萃取物已被廣泛研究。雖然有些已報導抗氧化活性及其他使用這些成份之健康裨益,作為抗氧化劑使用以治療曬傷皮膚或其他皮膚疾病並未建議山竹萃取物可提供任何口腔照護益處。有需要提供天然補充物,其對口腔提供抗菌、抗發炎以及抗氧化效用。
現已發現添加山竹(Garcinia mangostana L
.)萃取物至各種潔牙劑組成物,製成牙膏、漱口水、口香糖、口腔用條劑及其他組成物,其適宜於治療及防止各種口腔疾病,其包括:齒齦炎、牙菌斑堆積及其類似物。該山竹萃取物,含有氧葱酮及其他有益化學物質,可被加至潔牙劑組成物中,以致於使用時傳遞至口腔之量可有效提供抗菌、抗氧化及/或抗發炎效用。於各種具體實例中,除了山竹萃取物之外,該山竹萃取物之成份與天然萃取物結合以提供增強活性。
已發現以山竹萃取物合併其他天然萃取物配製之潔牙劑顯現抗菌、抗發炎及/或抗氧化性質,並有效治療口乾症,無需額外的抗菌劑。
依照一具體實例之特點,其提供一口腔用組成物,包含一有效量之山竹萃取物、一口腔可接受之載體,及除了山竹萃取物之外的天然萃取物。於一具體實例之另一特點,其提供一治療口腔軟組織之方法,包含投予口腔軟組織一組成物,該組成物包含一有效量之山竹萃取物、一口腔可接受之載體,及除了山竹萃取物之外的天然萃取物。
由以下提供之詳細說明,本發明進一步領域之應用性將很明顯。當指出本發明較佳具體實例時,應瞭解詳細說明及具體實例僅係為了說明之目的,並非為了限制本發明之範疇。
當通篇使用時,範圍被用作為速記文字以描述該範圍內各別及每一個值。任何範圍內之值可被選為該範圍之邊界。此外,於此引用之所有參考文將其全體併入作為參考。與本發明揭示內容及引用參考文獻之定義矛盾,以本揭示為主。此外,該組成物及方法可包含、實質上由下列組成或由下列組成:於此處所述之成份。
除非另有註明,於此處及說明書中之它處表示之所有百分比及量應被理解為意指重量百分比。給予之量係以該物質之活性重量為基準。此處一特定值之詳述係為了表示該值,加上或減少一定程度之變異以計算測量誤差,例如:10%之量可能包括9.5%或10.5%,給予測量之誤差程度將會被本發明所屬技術領域中具有通常知識者所領會及理解。
當於此使用時,此處“抗菌活性”意指由任何普遍接受之體外或體內抗菌試驗或檢驗所測定之活性。此處“抗發炎反應活性”意指由任何普遍接受之體外或體內試驗或檢驗所測定之活性,例如:對於前列腺素生產或環加氧酶活性抑制作用的試驗或檢驗。此處“抗氧化活性”意指由任何普遍接受之體外或體內抗氧化試驗或檢驗所測定之活性。
此處“口腔表面”包含口腔內任何軟或硬表面,包括舌頭表面、硬及軟顎、頰黏膜、齒齦及牙齒表面,此處“牙齒表面”係一天然牙齒之表面或人工齒列之硬表面,包括齒冠、齒蓋、填充物、牙橋、假牙、牙齒移植物及其類似物。此處專有名詞“抑制”,關於口腔組織中之症狀如發炎,其包含預防、壓制、降低程度或嚴重性,或改善症狀。
於此使用之“天然萃取物”表示任何由天然來源,諸如:植物、果實、樹木及其類似物獲得之萃取物。天然萃取物的非限定例子包括:牛膝草、木蘭、迷迭香、山茶(Camellia
)、桑色素、薑(zingiber officinale
)、肉荳蔻(Myristica fragrans
)、石榴(Punica granatum
)、洋棗(Zizyphus Joazeiro
)、柑橘(Jabara
)、印度假苦楝(Azadirachta indica
)、相思樹屬(Acacia
)、烏龍茶(Oolong tea
)、胡桃(Juglans regia
)、竹葉花椒(Zanthoxylum alantum
)、香欖(Mimusops elengi
)、黃葵(Hibiscus abelmoschus
)、阿育吠陀印度草藥(Ayurvedic
)、大花苦油楝(Carapa procera
)、非洲楝(Khaya senegalensis
)、山柑藤(Salvadora persica
)、葫蘆科(Cucurbitaceae
)(苦西瓜,Citrullus colocynthis
)及其類似物之萃取物。許多該萃取物係揭示於美國專利第6,264,926號及第7,083,779號,與美國專利申請案公開第2009/0087501號及第2007/0116652號。
本發明之口腔照護組成物可採用任何適宜用於口腔表面之形式。於各種說明性之具體實例中,該組成物可為適合沖洗、漂清或噴灑之液態溶液;潔牙劑,諸如:粉末、牙膏或牙膠;牙周膠;適合塗刷牙齒表面之液體,(例:液狀增白劑);口香糖;不可溶、部份不可溶或非不可溶性薄膜或條(例:增白條);薄片;手巾(wipe)或濕巾;移植物;漱口水、泡沫、牙線等。除以上列舉之外,該組成物可含有活性及/或載體組份。
於某些具體實例中,該組成物適合應用於小型家畜之口腔表面,例如:貓或狗。此組成物一般可被該動物食用或咀嚼,並且可採用例如貓或狗食、享受(treat)或玩具之形式。
作為活性劑或載體組份之成份於此之分類係由明確性及便利性決定,並無制訂依照其於此分類之組成物中特定組份之必要功能之結論。此外,一特定組份可做為多種功能,因此於此作為實例之一種功能屬性的組份揭示,並不能排除其亦可為另一功能屬性之實例的可能性。
於一個具體實例中提供牙膏組成物,其含有至少一來自山竹之萃取物、一口腔可接受之載體,及來自山竹之萃取物之外的天然萃取物。山竹(Garcinia mangostana
L.)(“山竹(Mangosteen)”)係一常綠樹,十至二十五公尺高。由於其可口風味,山竹果實常被稱為“果中之后”。山竹果實係具有稍微平坦端之圓形,以及直徑為6至7公分。其具有光滑厚實堅固的外皮,當未成熟時為淡綠色,成熟時為暗紫或紅紫色。外皮包圍4至8片白色可食用果肉。有些果實不具種子(無籽),而其他果實具有1至5個完全發育之種子。
“山竹(Mangosteen)”係專有名詞,其通常意指該植物,且亦作為一形容詞,如:“山竹果皮”、“山竹萃取物”、“山竹化合物”或“山竹組成物”,此後兩個專有名詞意指該植物之萃取物、由該植物產生之化合物,以及包含此化合物之組成物。本發明於此所述之具體實例提供天然化合物,較佳係萃取自山竹植物之氧葱酮。據認為萃取自山竹之0.01%至85%濃縮物(例:萃取自山竹外皮之氧葱酮)以及其合併除了山竹萃取物之外的天然萃取物配製為一潔牙劑組成物,其提供改良的抗發炎、抗菌及抗氧化功效。於本發明之具體實例中,存在於山竹萃取物之氧葱酮的量係介於萃取物總重0.01%至85%,特別是範圍介於0.3%至60%,以及更特別是介於1%至40%之量。其他特定具體實例包括含有組成物總重的1%、10%、20%及40%的量之氧葱酮的萃取物組成物。
若該山竹萃取物含有氧葱酮,較佳該富含氧葱酮之萃取物包含以下氧葱酮類中之至少一種:卡拉巴氧葱酮(calabaxanthone)、去甲基卡拉八氧葱酮(demethylcalabaxanthone)、6-去氧-γ-楝子素、1-異楝子素、3-異楝子素、1-異楝子素水合物、3-異楝子素水合物、加沓寧(gartanin)、8-去氧加沓寧、加西農(garcinone)A、加西農B、加西農C、加西農D、加西農E、山竹醇(mangostanol)(平基(prenyl)氧葱酮)、山竹醇(多氧化(polyoxygenated)氧葱酮)、α-楝子素、β-楝子素、γ-楝子素、山竹果呫吨酮(mangostinone)、1,5-二羥基-2-(3-甲基丁-2-烯基)-3-甲氧基氧葱酮、1,7-二羥基-2-(3-甲基丁-2-烯基)-3-甲氧基氧葱酮、1,5-二羥基-3-甲氧基-2-(3-甲基丁-2-烯基)氧葱酮、1,7-二羥基-3-甲氧基-2-(3-甲基丁-2-烯基)氧葱酮、5,9-二羥基-2,2-二甲基-8-甲氧基-7-(3-甲基丁-2-烯基)-2H,6H-哌喃[-3,2b]-6-酮、2-(.γ.,.γ.-二甲基烯丙基)-1,7-二羥基-3-甲氧基氧葱酮、2,7-二-(3-甲基丁-2-烯基)-1,3,8-三羥基-4-甲基氧葱酮、2,8-二-(3-甲基丁-2-烯基)-7-羧基-1,3-二羥基氧葱酮、非楝子素(normangostin)(ν-楝子素)、1,5,8-三羥基-3-甲氧基-2-(3-甲基-2-丁烯基)氧葱酮、1,7-二羥基-2-異平基(isoprenyl)-3-甲氧基氧葱酮、氧葱酮1、BR-氧葱酮A、BR-氧葱酮B(2,4,5-三羥基-1-甲氧基氧葱酮)、加西農B、山竹醇、山竹酚(mangostenol)、山竹酮(mangostenone)A、山竹酮B、拖沃費林(tovophyllin)及粹普立福力氧葱酮(trapezifolixanthone),並可包括存在於外皮之任何及所有活性植物性化合物,或其組合。
作為一種氧葱酮較佳來源,山竹萃取物可被使用範圍為0.01%至5%重量比,例如:0.01%至2%重量比及0.1%至1%重量比於牙膏組成物中。於各種具體實例中,牙膏組成物更含有其他抗菌劑,諸如鹵化二苯醚,例如:三氯沙、氣化鯨蠟基吡啶鎓(cetyl pyridinium chloride)及其類似物。牙膏組成物亦含有一額外天然萃取物,其可存在量範圍由0.01%至5%重量比,例如:0.01%至2%重量比及0.1%至1%重量比於牙膏組成物中。
於另一具體實例中,本發明提供一種在動物對象的口腔中抑制細菌生長及/或發炎反應之方法。該方法較佳係一種治療口腔軟組織之方法,其包含投予一組成物至口腔軟組織,該組成物包含一有效量之來自山竹的萃取物、一口腔可接受之載體,及來自山竹之萃取物之外的天然萃取物。
於另一具體實例中,本發明提供漱口水或口腔洗劑,其包含水、香料及至少一種含氫之成份,諸如乙醇、甘油及山梨醇,一起與來自山竹之萃取物,及來自山竹之萃取物之外的天然萃取物。於另一具體實例中,該發明提供口香糖,除了來自山竹之萃取物及來自山竹之萃取物之外的天然萃取物,其包含膠基質及香料。於進一步具體實例中提供食用條,除了來自山竹之萃取物及來自山竹萃取物之外的天然萃取物,其含有形成薄膜之聚合物及視情況之香料。
在一方面,該組成物含有來自山竹之萃取物之外的天然萃取物。可使用任何合適萃取物,只要其可增強來自山竹之萃取物的抗菌、抗發炎及抗氧化功效之。合適萃取物包括例如:牛膝草、木蘭、越橘、迷迭香、山茶、桑色素、薑、肉荳蔻、石榴、洋棗、柑橘、印度假苦楝、相思樹屬、烏龍茶、胡桃、竹葉花椒、香欖、黃葵、阿育吠陀印度草藥、大花苦油楝、非洲楝、山柑藤、葫蘆科(苦西瓜)及其類似物之萃取物。
特別佳之萃取物包括:牛膝草、木蘭、越橘、迷迭香、山茶、桑色素、薑、肉荳蔻、石榴、洋棗、柑橘、印度假苦楝、相思樹屬、烏龍茶(Oolong tea
)、胡桃、竹葉花椒、香欖、黃葵、阿育吠陀印度草藥、大花苦油楝、非洲楝、山柑藤、葫蘆科(苦西瓜)、阿仙藥(Acacia catechu
)、阿拉伯金合歡(Acacia nilotica
)、土牛膝(Achyrathes aspera
)、印度假苦楝(Azadirachta indica
)、馬兜鈴(Aristolochia bracteolate
)、樟樹(Cinnamomum camphora
)、錫蘭肉桂(Cinnamomum verum
)、鬱金(Curcuma longa
)、藍桉樹(Eucalyptus globulus
)、囊葉榕(Ficus bengalensis
)、胡桃、長葉馬府油樹(Madhuca longifolia
)、香欖、九層塔(Ocimum sanctum
)、烏龍茶(Oolonga tea)、荖花(Piper betel)葉、蓽撥(Piper longum
)、胡椒(Piper nigrum
)、西南委陵菜(Potentilla fulgens
)、丁香(Syzygium aromaticum
)、菊科植物(Spilanthes calva
)、大果苔莓(Vaccinium macrocarpon
)、秦椒(Zanthoxylum armatum
)之萃取物,及其混合物。
額外之萃取物可選自下列屬中之一或多種植物:牛至屬(Origanum
)、百里香屬(Thymus
)、薰衣草屬(Lavandula
)、鼠尾草屬(Salvia
)、香蜂草屬(Melissa
)、小茴香屬(Cuminum
)、荷蘭水芹屬(Petroselinum
)、金盞花屬(Calendula
)、萬壽菊屬(Tagetes
)、乳香屬(Boswellia
)、接骨木屬(Sambucus
)、苦配巴香脂樹(Copaifera
)、薑黃屬(Curcuma
)、蔥屬(Allium
)、康福利草(Symphytum
)、石榴屬(Punica
)、甘藍椰子屬(Euterpe
)、槐樹屬(Sophora
)、大黃屬(Rheum
)、蕎麥屬(Fagopyrum
)、山茶屬(Camellia
)、黃連屬(Coptis
)、白毛茛屬(Hydrastis
)、十大功勞屬(Mahonia
)、黃檗屬(Phellodendron
)、小檗屬(Berberis
)、黃根樹(Xanthorhiza
)、忍冬屬(Lonicera
)、越橘屬(Vaccinium
)、肉桂屬(Cinnamomum
)、葡萄屬(Vitis
)、欖仁樹屬(Terminalia
)、松屬(Pinus
)、大葉合歡屬(Albizia
)、楝樹屬(Melia
)、山柑藤屬(Salvadora
)、香無患子屬(Paullinia
)、胡椒屬(Piper
)、蒲桃屬(Syzygium
)、沒藥樹屬(Commiphora
)、胡桃屬(Juglans
)、黃芩屬(Scutellaria
)及木蘭屬(Magnolia)。
更具體而言,使用於此處所述之組成物的額外天然萃取物可萃取自以下種類之植物:牛至(Origanum vulgare
)、馬郁蘭(Origanum onites
)、香牛至(Origanum majorana
)、冬牛至(Origanum heracleoticum
)、木立百里香(Thymus vulgaris L
)、檸檬百里香(Thymus citriodorus
)、寬葉百里香(Thymus pulegioides
)、葛縷子百里香(Thymus xherba-barona
)、鋪地百里香(Thymus serpyllum)、狹葉薰衣草(Lavandula angustifolia
)/藥用薰衣草(Lavandula officinalis
)、寬葉薰衣草(Lavandula stoechas
)、齒葉薰衣草(Lavandula dentate
)、醒目薰衣草(Lavandula x intermedia
)、蕨葉薰衣草(Lavandula multifida
)、藥鼠尾草(Salvia officinalis
)、洋蘇草(Salvia divinorum
)、白鼠尾草(Salvia apiana
)、香水薄荷(Melissa officinalis
)、小茴香(Cuminum cyminum
)、荷蘭水芹(Petroselinum crispum
)、金盞花(Calendula arvensis
)、馬德拉金盞花(Calendula maderensis
)、大金盞花(Calendula officinalis
)、萬壽菊(Tagetes erecta
)、墨西哥萬壽菊(Tagetes minuta
)、細葉萬壽菊(Tagetes patula
)、乳香木(Boswellia sacra
)、野地乳香(Boswellia frereana
)、返魂香(Boswellia serrata
)、構乳香(Boswellia papyrifera
)、西洋接骨木(Sambucus nigra
)、黑接骨木(Sambucus melanocarpa
)、歐洲接骨木(Sambucus racemosa
)、藍氏香脂蘇木(Copaifera langsdorfii
)、鬱金(Curcuma longa
)、蒜(Allium sativu
)、康福利草(Symphytum officinale
)、石榴(Punica granatum
)、嫩葉甘藍椰子(Euterpe oleracea
)、苦參(Sophora flavescens
)、波葉大黃(Rheum rhabarbarum
)、圓葉大黃(Rheum rhaponticum
)、蕎麥(Fagopyrum esculentum
)、中華山茶(Camellia sinensis
)、黃連(Coptis teeta
)、白毛茛(Hydrastis canadensis
)、尖頭葉十大功勞(Mahonia aquifolium
)、黃檗(Phellodendron amurense
)、刺小檗(Berberis vulgaris
)、黃根樹(Xanthorhiza simplicissima
)、忍冬(Lonicera ceprifoliu
)、大果苔莓(Vaccinium macrocarpon
)、錫蘭玉桂(Cinnamomum zeylanicum Nees
)、錫蘭肉桂(Cinnamomum verum
)、歐洲葡萄(Vitis Vinifera
)、紅果欖仁樹(Terminalia Bellerica
)、海岸松(Pinus Pinaster
)、大葉合歡(Albizia Lebbek
)、印度楝(Melia Azadirachta
)、山柑藤(Salvadora persica
)、瓜拿納(Paullinia cupana
)、荖葉(Piper betle
)、丁香(Syzygium aromaticum
)、沒藥(Commiphora myrrha
)、胡桃(Juglans regia
)、黃芩(Scutellaria baicalensis
)及厚朴(Magnolia officinalis
)。
與山竹萃取物一起之有用額外天然萃取物亦可選自下列天然萃取物中之一或多種(包括前方非斜體之俗名,之後為斜體之學名):牛膝,牛藤(Achyranthes aspera
);蘆薈,蘆薈屬,包括翠葉蘆薈(A. barbadensis
)、好望角蘆薈(A. ferox
)及庫拉索蘆薈(A. vera
);大茴香,大茴香
(Pimpinella anisum
);馬兜鈴,馬兜鈴(Aristolochia bracteolate
);金車菊,金車菊屬,包括山金車菊(Arnica fulgens
);榕樹,囊葉榕(Ficus bengalensis
);巴古拉木,香欖(Mimusops elengi
);羅勒,甜羅勒(Ocimum basilicum
)及小羅勒(O. minimum
);蒟醬,荖葉(Piper betle
);黑胡椒,胡椒(Piper nigrum
);樟腦,樟樹(Cinnamomum camphora
);兒茶,阿仙藥(Acacia catechu
);白屈菜,白屈菜屬(Chelidonium spp.
);甘菊,西洋甘菊(Matricaria chamomilla
);訶子,毗梨勒(Terminalia chebula
);中黃芩,黃芩(Scutellaria baicalensis
);肉桂,牡桂(Cinnamomum lourerii
)及肉桂醛(C. zeylandicum
);柑橘,柑橘屬,包括來檬(C. aurantifolia
)、臺灣香檬(C. aurantium
)、香櫞(C. limonum
)及甜橙(C. sinensis
);丁香,丁香(Syzygium aromaticum
);蒔蘿,蒔蘿屬,包括小茴香(A. graveolens
)及印度蒔蘿(A. sowa
);紫錐菊(黃雛菊),淡紫松果菊(Echinacea pallida
);桉樹,藍桉樹(Eucalyptus globulus
);茴香,茴香(Foeniculum vulgare
);梔子,梔子(Gardenia jasminoides
);薑,薑(Zingiber officinale
);葡萄,歐洲葡萄(Vitis vinifera
);蛇麻草,啤酒花(Humulus lupulus
);魚腥草,蕺菜(Houttuynia cordata
);印地安桑樹,檄樹(Morinda citrifolia
);杜松,歐洲刺柏(Juniperus communis
);檸檬草,香茅草屬,包括檸檬草(C. citratus
)及檸檬香茅(C. flexuosus
);歐亞甘草,甘草屬,包括甘草(G. glabra
)及烏拉爾甘草(G. uralensis
);蓽撥(馬蹄荷木),蓽撥(Piper longum
);紫荊木,長葉馬府油樹(Madhuca longifolia
);木蘭,厚朴(Magnolia officinalis
);金盞花,大金盞花(Calendula officinalis
);乳香,乳香(Pistacia lentiscus
);木樨,黃香草木樨(Melilotus officinalis
);蓍草,西洋蓍草(Achillea millefolium
);沒藥,沒藥樹屬,包括阿比尼西亞沒藥(C. abyssinica
)及沒藥(C. molmol
);印楝樹(諾楝樹),印度假苦楝(Azadirachta indica
);橙花(苦橙花),酸橙(Citrus aurantium
);肉荳蔻(荳蔻),肉荳蔻(Myristicafragrans
);五倍子,沒食子櫟(Quercus infectoria
);荷蘭芹,荷蘭水芹(Petroselinum sativum
);皮魯(peelu),山柑藤(Salvadora persica
);薄荷,西洋薄荷(Mentha piperita
);松樹,松屬,包括大王松(P. palustris
)及歐洲赤松(P. sylvestris
);石榴,石榴(Punica granatum
);多刺金合歡(假阿拉伯膠樹),阿拉伯金合歡(Acacia nilotica
);豆科植物拉坦捏(rhatany),拉坦捏屬,包括銀拉坦捏(K. argentea
)及巴西拉坦捏(K. triandra
);迷迭香,迷迭香(Rosmarinus officinalis
);番紅花,番紅花(Crocus sativus
);鼠尾草,鼠尾草屬,包括山艾(S. lavendulaefolia
)、藥鼠尾草(S. officinalis
)及三裂葉鼠尾草(S. triloba
);檀香,檀香屬,包括白檀(S. album
)及澳洲檀香(S. spicatum
);綠薄荷,綠薄荷(Mentha spicata
);千日菊(阿卡拉香料(akarkara)),金鈕扣花(Spilanthes calvi
);八角茴香,大茴香(Illicium verum
);茶(包括綠茶與烏龍茶),中華山茶(Camellia sinensis
);百里香,百里香屬
,包括鋪地百里香(T. serpyllum
)及木立百里香(T. vulgaris
);托馬爾(tomar)(花椒),秦椒(Zanthoxylum armatum
);圖爾西(tulsi)(聖羅勒),九層塔(Ocimum sanctum
);薑黃,鬱金(Curcuma longa
);松蘿,須松蘿(Usnea barbata
);法蘭丹堤(vajradanti),西南委陵菜(Potentillafulgens
);胡桃,胡桃(Juglans regia
);冬青樹,矮冬青
(Gaultheria procumbens
),及其混合物。
如本文討論,該額外之天然萃取物可衍生自或基於自植物分離之化合物或萃取物。下列每一個植物提供一或多種活性組份,其於口腔用組成物中有利於一或多項口腔照護裨益。例如:來自迷迭香(Romains officinalis
)(迷迭香)之萃取物具有抗菌及抗發炎功效。迷迭香萃取物含有多種有機及無機物質,包括類黃酮、三萜酸及酚酸。有利的有機化合物之非限定實例包括:1,8-桉醚、樟腦、a-蒎烯、鼠尾草酸、迷迭香酸、熊果酸、鼠尾草醇及丁香油素。此處所含有與多種萃取物相關之活性化合物的討論包括那些被認為對口腔用組成物有效之化合物;然而,表列之化合物係非排它性,且於某些案例中尚未鑒別或完全特徵化,但實驗觀察證實所欲之效果。此外,於各個方面,包含此處所含有之所有化合物的完整萃取物提供最有效之植物活性組份。Trivedi等人之美國專利申請案公開第2006/0134025號探討使用於口腔用組成物之迷迭香萃取物,並授權予高露潔公司(Colgate-Palmolive)。迷迭香植物葉之萃取物以迷迭香萃取物由例如:紐澤西‧皮斯卡塔威之沙賓沙公司(Sabinsa Corporation of Piscataway)出售。此些於各種植物基底萃取物發現之化合物可由該萃取物分離,並作為植物活性組份單獨使用。例如:當其被發現可有效對抗造成齲齒、齒齦炎及口臭之口腔細菌,鼠尾草酸可被單獨分離並用於口腔用組成物中。
依照目前教示之其他有益萃取物包括來自唇形科(Lamiaceae
family)之任何適宜的植物部份,包括那些分類為以下屬別之植物:牛至草屬、百里香屬、薰衣草屬、鼠尾草屬、分藥花屬(Perovskia
)、糙蘇屬(Phlomis
)或香蜂草屬。例如:適宜之萃取物包括那些來自牛至(Origanum vulgare L
.)(俗名為“牛膝草”、“野生牛膝草”或“野生馬鬱蘭(wild marjoram)”),包括其亞種(牛至亞種(Origanum vulgare ssp.
)),馬郁蘭(Origanum onites
)(俗名為“義大利牛膝草(Italian oregano)”或“罐馬鬱蘭(pot marjoram)”)。香牛至(俗名為“馬鬱蘭”或“甜馬鬱蘭”)及冬牛至。牛至亞種包括土茵陳(O. vulgare ssp. vulgare
)、綠牛至(O. vulgare ssp. viride
)及紅牛至(O. vulgare ssp. hirtum
)(俗名為“希臘牛膝草”或“野生牛膝草”)。於此使用之專有名詞“牛膝草”涵蓋所有牛至草屬之適宜種及亞種。牛膝草被認為含有超過30種活性化合物,包括香芹酚(carvacrol)、百里酚及迷迭香酸。
百里香屬(百里香)亦屬於唇形科,包括超過三百個種及亞種。適宜之萃取物包括那些分離自以下植物之萃取物:木立百里香(Thymus vulgaris L
)、檸檬百里香(T. citriodorus
)、寬葉百里香(T. pulegioides
)、葛縷子百里香(T. x herba-barona
)及鋪地百里香(T. serpyllum
)。於此使用之專有名詞“百里香”涵蓋所有百里香屬之適宜種及亞種,且其萃取物被認為含有香芹酚及百里酚活性化合物。
其他適宜之萃取物包括那些來自薰衣草屬(薰衣草),其涵蓋超過30個種。適宜之薰衣草種類包括狹葉薰衣草(Lavandula angustifolia
)(從前已知為藥用薰衣草(L. Officinalis L.
))、寬葉薰衣草(L. stoechas
)、齒葉薰衣草(L. dentate
)、醒目薰衣草(L. x intermedia
)及蕨葉薰衣草(L. multifida
)。薰衣草萃取物含有活性化合物乙酸沉香酯及沈香醇。於此使用之專有名詞“鼠尾草”一般包括唇形科的三個屬,名為鼠尾草屬、分藥花屬(Perovski
)及糙蘇屬。於某些方面,有益植物包括藥鼠尾草(Salvia officinalis
)(一般鼠尾草)、洋蘇草(S. divinorum
)(占卜者鼠尾草)及白鼠尾草(S. apiana
)(白鼠尾草)。來自藥鼠尾草之萃取物尤其具有抗菌、抗真菌及止血功效。取自檸檬香脂植物(香水薄荷(Melissa Officinalis
))之另一適宜萃取物具有抗菌及抗病毒性質。
依照目前具體實例之進一步有益萃取物亦包括那些源自繖形花科(Apiaceae family
)之植物,包括小茴香屬及荷蘭水芹屬。小茴香(Cuminum cyminum
)(小茴香(Cumin))含有各種活性化合物,包括茴香甲醛及吡嗪。荷蘭水芹(Petroselinum crispum
)(荷蘭芹(parsley))包含芹菜腦、呋喃香豆素(furanocourmarin)及補骨脂素(psoralen)化合物。小茴香及荷蘭芹之萃取物具備有益抗氧化活性及其它有益功效。
金盞花屬(Genera Calendula
)及萬壽菊屬兩者一般已知為“金盞花(marigold,)”,皆為菊科(familyAsteraceae
)。金盞花屬包括許多種及亞種,包括金盞花(Calendula arvensis
)(田野金盞花)、馬德拉金盞花(C. maderensis
)(馬德拉金盞花(Madeiran marigold))及大金盞花(C. officinalis
)(壺金盞花(pot marigold))。金盞花屬萃取物含有各種活性化合物,包括金盞酸(calendic acid)。萬壽菊屬包括超過60個種及亞種,包括萬壽菊(Tagetes erecta
)、墨西哥萬壽菊(T. minuta
)、細葉萬壽菊(T. patula
)等。金盞花屬及萬壽菊屬兩者之萃取物具有抗氧化及抗發炎活性,且可有效對抗造成齲齒、齒齦炎及口臭之口腔細菌。
乳香屬係樹木之屬,其產生具抗發炎性質之萃取物,包括乳香酸化合物。例如:乳香木(Boswellia sacra
)、野地乳香(B. frereana
)、返魂香(B. serrata
)及構乳香(B. papyrifera
),以及其亞種產生之適宜萃取物。分離自乳香屬植物之有益活性化合物係乙醯基酮β-乳香酸(acetyl keto.beta.-boswellic acid(AKBBA)),例如:3-乙醯基11-酮β-乳香酸,其表現抗菌、抗發炎及抗氧化活性。可商業取得之返魂香萃取物包括由沙賓沙公司(Sabinsa Corp.)取得之名為BOSWELLINCG之β-乳香酸及有機酸之混合物。
接骨木屬包括超過30個種及亞種,其一般稱為接骨木(elderberry)或接骨木(elder)。各種接骨木種類皆適宜,尤其包括西洋接骨木(Sambucus nigra
)(一般接骨木)、黑接骨木(S. melanocarpa
)(黑莓接骨木)、歐洲接骨木(S. racemosa
)(紅漿果接骨木)。接骨木萃取物已被發現具有抗氧化活性,並進一步於口腔用組成物中提供一或多種下列益處:抗菌、抗氧化、抑制膠原蛋白酶、活化去乙醯化酶(sirtuins)及抗發炎性質。
因其係鬱金(Curcuma longa
)(薑黃),藍氏香脂蘇木(Copaifera langsdorfii
)(苦配巴香脂(copaiba balsam))之萃取物係有益的,其包含化合物:薑黃素、去甲氧基薑黃素、雙去甲氧基薑黃素及四氫類薑黃素(tetrahydrocurcuminoid)。額外之適宜萃取物包括那些分離自蒜(Allium sativum
)(大蒜)或蔥屬之其他植物的萃取物。大蒜萃取物含有蒜素、蒜胺酸、大蒜烯(ajoene)及其他類黃酮,其提供抗氧化及/或抗微生物益處。來自康福利草(Symphytum officinale
)(紫草料植物)或其他康福利草屬之植物的萃取物為有效抗氧化、抗發炎及/或抗微生物劑;作為石榴(Punica granatum
)(石榴)萃取物,其包括各種抗氧化多酚,諸如:可水解單寧安石榴苷(hydrolyzable tannins punicalagins);嫩葉甘藍椰子(Euterpe oleracea
)(阿薩伊棕櫚(Acai palm))含有白藜蘆醇、花青素及各種其他類黃酮,以及類黃酮相似化合物,諸如:異葒草苷(homoorientin)、葒草苷(orientin)、双氫槲皮素(tasifolin)、去氧己糖、異牡荊素(isovitexin)、金雀花素;苦參(Sophora flavescens
)萃取物含有苦參素(kurarinone),作為一生物活性類黃酮,其具有抗發及抗菌功能。上述每一種萃取物表現一或多種抗氧化、抗發炎、抗病毒及/或抗菌性質。苦參素的代表性結構為:
於某些揭示方面,該口腔用組成物視情況包含源自鬱金(C. longa
)之商業取得的萃取物,其包含四氫類薑黃素,商品名稱為SABIWHITE,由沙賓沙公司(Sabinsa Corp.)取得,其被認為具有以下代表結構:
各種植物萃取物含有該活性化合物─芸香苷(槲皮素-3-芸香糖苷),其係一抗氧化類黃酮醣苷(包含黃酮醇槲皮素及雙醣芸香糖),發現於蓼(Polygonaceae)科之各種植物,包括大黃屬,包括波葉大黃(Rheum rhabarbarum
)及圓葉大黃(R. rhaponticum
)(食用大黃),以及蕎麥芒什(Fagopyrum esculentum
Moench)(蕎麥)植物。認為之代表結構表示如下:
芸香苷被認為可清除超氧化物基、螯合金屬離子、調節嗜中性球爆裂、抑制脂質過氧化反應、維持生物性抗氧化降低之麩胺硫,以及具有涉及芬頓(fenton)反應(其產生活性氧物種)。因此,芸香苷具有抗氧化、抗發炎、抗癌、抗血栓、細胞保護(cytoprotective)及血管保護(vasoprotective)之活性,其對口腔用組成物有益。此外,芸香苷增強口腔用組成物之抗牙菌斑及抗氧化活性。
抗菌、抗氧化劑及/或抗發炎之天然萃取物的非限定實例包括那些分離自綠茶或烏龍茶、肉桂、金線(gold thread)、越橘及其他杜鵑花科植物,金銀花(honeysuckle)、葡萄籽、印度苦茶(myrobalan)、迷迭香、東印地安胡桃(east Indian walnut)、印楝樹(neem)、葉下珠(niruri)及松樹樹皮之萃取物。
綠茶及烏龍茶分離自中華山茶(Camellia sinensis
)。可使用中華山茶之任何變種、形式或亞種,且可選自其任何亞種分類單位,適宜之例子為:阿薩姆茶(C. sinensis var. assamica
),其包括例如:前者之苦茶(C. assamica
)及苦茶變種(var. kucha
);高棉茶(C. sinensis var. cambodiensis
),其包括例如:前者之亞種盾葉高棉茶(lasiocalyx
)及向變種高棉茶(var. Shan
);德宏茶(C. sinensis var. dehungensis
);白毛茶(C. sinensis var. pubilimba
)及香花茶(C. sinensis var. sinensis
),其包括例如:前者之武夷變種(vars. bohea
)、大葉變種(macrophylla
)、小葉變種(parvifolia
)及香花茶變種(waldenae
)。中華山茶萃取物之活性成份被認為係多酚兒茶素(polyphenol catechine),其包括兒茶素、前兒茶素(epocatechin)、表沒食子兒茶素(epigallocatechin)、表兒茶素沒食子酸酯(epicatchin gallate)、沒食子兒茶素(gallocatechin)及表沒食子兒茶素。Worrell於美國專利公開第2006/0141073號敘述使用於口腔用組成物之未氧化山茶(例:綠茶)的萃取物,及Boyd等人於美國專利公開第2006/0141039號敘述氧化山茶(例:烏龍茶)的萃取物,兩者皆授權予高露潔公司(Colgate-Palmolive)。一適宜山茶萃取物之實例為“綠茶萃取物CG”,說明書編號MS-0726-01,可自沙賓沙公司獲得。
金線萃取物可由以下植物科中之一或多種獲得:番荔枝科(Annonaceae
)、小檗科(Berberidaceae
)、防已科(Menispermaceae
)、罌粟科(Papaveraceae
)、毛茛科(Ranunculaceae
)、芸香科(Rutaceae
)、囊荷科(Zingiberaceae
)、納迪納科(Nadina
)、十大功勞科(Mahonia
)及唐松草屬(Thalictrum spp
)。例如:於口腔照護組成物中具有所欲優點之金線萃取物為黃連(Coptis teeta)(黃連屬)。小蘗鹼(抗發炎、抗微生物之化合物)被認為係金線萃取物之活性化合物。金印草(Goldenseal
)(橘根),白毛茛,屬於毛茛科,且其活性成份之一被認為係小蘗鹼及白毛茛鹼生物鹼(hydrastine alkaloids)。其他具有小蘗鹼為活性化合物之萃取物包括:尖頭葉十大功勞(Mahonia aquifolium
)(奧勒岡葡萄)、黃檗(Phellodendron amurense
)(黃檗屬)、刺小檗(Berberis vulgaris
)(伏牛花)及黃根樹(Xanthorhiza simplicissima
)(黃根)。
忍冬(Honeysuckle)(忍冬(Lonicera ceprifolium
))萃取物可由忍冬植物之花獲得。於忍冬萃取物中的活性多酚物質被認為係漂木酸及/或木犀草素(lutenolin
)類黃酮。杜鵑花科泛指超過100屬及超過4,000相關種,譬如那些Sanker等人揭示於美國專利第5,980,869號之植物。於某些具體實例中,來自越橘屬植物之萃取物係有益之抗菌天然萃取物,諸如越橘(大果苔莓)。
錫蘭玉桂或錫蘭肉桂被認為包含多種活性化合物,包括桂皮醛、丁香酚、桂皮酸乙酯、β-石竹烯、沈香醇及甲基佳味酚。肉桂萃取物展現抗氧化及抗菌活性。葡萄籽或葡萄皮之萃取物係分離自歐洲葡萄植物,且包含各種多酚,包括:白藜蘆醇及抗氧化花青素原(proanthocyanidins)。印度苦茶最好萃取自紅果欖仁樹果實。松樹樹皮萃取物最好萃取自海岸松(沿海松)之皮層(樹皮),其包含碧蘿芷(pycnogenol)
,並表現抗菌、抗發炎、抗氧化及抗老化活性。印楝樹或諾楝樹(印度楝)植物之皮層萃取物係已知之抗菌成份。葉下珠或珠子草(Phyllanthus Niruri
)之萃取物亦為已知之抗菌萃取物。山柑藤(健齒植物(miswak))之萃取物於口腔照護組成物中提供有效抗菌效果。在某些方面,額外之天然萃取物可自瓜拿納(瓜拿納植物(guarana))分離,其萃取物包括:咖啡鹼、兒茶素、可可豆鹼、茶鹼及其他生物鹼。
荖葉(蒟醬(betel))萃取物,特別是源自蒟醬葉之萃取物,被認為包含活性化合物,諸如:甲氧蒟酚、佳味酚、草嵩腦、丁香酚、甲基丁香酚及羥基兒茶酚。丁香(丁香(clove))萃取物具有抗菌及麻醉性質,並包含化合物例如:丁香酚、β-丁香醇(β-caryophylline)、香草醛、山楂酸(crategolic acid)、柳酸甲酯、單寧、黃酮類化合物(包括丁香寧、番鬱金黃素、鼠李素及丁香素(eugentitin))、三萜皂苷(諸如:丁香油素、豆固醇及油菜籽固醇)及各種倍半萜。沒藥(沒藥(myrrh))同樣有益於口腔用組成物,提供抗微生物及抗發炎益處。另一適宜之植物屬係胡桃屬,包括胡桃(波斯胡桃木或一般胡桃樹),其萃取物具抗發炎及抗氧化性質。東印度胡桃(大葉合歡)之葉同樣地適宜用作為萃取物。
於某些具體實例中,於此所述之組成物的額外天然萃取物包含至少一種自由B環類黃酮(free-B-ring flavonoid)。類黃酮係一群化合物,包括此類化合物如:黃酮、黃烷、黃酮醇、黃烷酮醇(dihydroflanonol)、黃烷酮(flavonone)及其衍生物。Xu等人於美國專利公開第2006/0140881號敘述使用於口腔用組成物之自由B環類黃酮活性組份,並授權予高露潔公司。
於各種具體實例中,額外之天然萃取物可包含自由B環類黃酮,其意指類黃酮化合物,其普遍含有2,3-雙鍵及/或4-側氧基,且芳香族B環上缺乏任何取代基。Xu等人於美國專利公開第2006/0140881號敘述此口腔用組成物之活性組份,並授權予高露潔公司。自由B環類黃酮可分離自唇形科植物,特別是那些黃芩(Scutellarioideae
)亞科植物。例如:該黃芩(Scutellaria baicalensis
)種含有大量自由B環類黃酮,包括:貝加因(baicalein)、貝加黃酮(baicalin)、黃芩素(wogonin)及黃芩糖苷(baicalenoside)。自由B環類黃酮具有抗氧化及抗發炎性質,並抑制環加氧酶COX-2一般活性。在某些方面,額外之天然萃取物可視情況包含貝加黃酮(中文名稱亦為“黃芩苷”)、5,6-二羥基黃酮-7-O-葡萄糖苷,及貝加因(中文名稱亦為“黃芩素”)、5,6,7-三羥基黃酮。於各種具體實例中,本揭示之口腔用組成物的額外天然萃取物可包含貝加黃酮、貝加因,及其混合物。
來自木蘭(Magnoliaceae
)科,諸如厚朴(木蘭)之植物含有活性化合物,包括:厚朴酚(magnolol)、和厚朴醇(honokiol)、四氫厚朴酚及四氫和厚朴醇,其已被證實具對抗多種口腔細菌之殺菌性質。在各種方面,厚朴酚及/或和厚朴醇係有益之抗菌植物活性組份。Trivedi等人於美國專利公開第2006/0134024號及Xu等人於專利公開第2006/0127329號敘述來自木蘭萃取物之活性化合物的使用,兩者皆授權予高露潔公司。
已知抗微生物、抗氧化及/或抗發炎劑之其他適宜天然萃取物列入於International Cosmetic Ingredient Dictionary and Handbook,Tenth Ed.,2004。
可根據已知方法製備山竹萃取物,其經由酒精萃取酒精可溶性成份,或自冷凍乾燥磨碎之山竹葉、樹皮、果實等,或自山竹之外皮或果皮。其他山竹之適宜萃取物可取自山竹樹之樹皮。已知各種萃取程序,並描述於文獻尤其是Fan等人“Antioxidative Mechanism of Isolated Components from Methanol Extract of Fruit Hulls ofGarcinia mangostana L.
,”Chinese Agriculture Chem.
Soc.5,540-51,(1997);Nilar;Harrison LJ.,“Xanthones from the heartwood ofGarcinia mangostana
,”Phytochemistry
,60,541-8(2002)。
自植物萃取固體或液體原料通常涉及以一適當溶劑接觸該原料,以自原料中移出所欲自原料萃取之物質。當該原料係固體時,較好在其與溶劑接觸前乾燥並粉碎或磨碎該原料。可經由該領域熟諳技術人士已知習用方法進行此萃取,例如:經由使用萃取設備,諸如:Soxhlet儀器,其保留固體原料於一支架上,並使溶劑流經該原料;經由一起摻合溶劑及原料,之後分離液及固相或兩不溶混之液相,諸如:經由過濾或經由沉澱及傾析。於各種具體實例中,使用於口腔照護組成物之植物活性組份為可再生、品質穩定且具微生物安全性。
製備山竹萃取物之一種方法包括以萃取溶劑萃取植物原料,諸如:甲醇、異丙醇、丁醇、二甲苯、苯或甲苯,並濃縮及結晶來自萃取溶劑之粗產物。當該產物可作為萃取物使用時,額外程序可有益於純化某些萃取成份。例如:該粗產物可溶於二醇與視情況上述溶劑中之一,該溶解之粗產物之後可分佈於該溶劑相及二醇相之間。若上述溶劑中之一未與二醇加入,則在分佈至兩相之間前,加入一或多種該溶劑,以及若已加入該溶劑之一,在分佈過程前加入更多溶劑。濃縮該溶劑相,並由濃縮物中再結晶萃取物。經回顧此處敘述,對那些熟諳該領域技術人士,製備山竹萃取物之其他方法將顯而易見。
選擇在各種口腔用組成物中成份之治療量(treatment levels),以傳遞有效量之山竹萃取物至動物個體的口腔表面,其中施加口腔用組成物。例如:於牙膏及牙膠中,於此所述之萃取物組合物的適宜濃度為包含0.01%重量比至5%重量比,例如:0.05至5%重量比,及特別是0.1至0.3%重量比。
至於牙粉,該治療量大致與牙膏及牙膠相同,而至於漱口水及洗劑,傾向於較少治療量。例如:漱口水及口腔洗劑含有0.01%至2%重量比之萃取物組合物,例如:由0.01%至0.6%、0.01%至0.2%,及0.01至0.05%。此外,口香糖、塗敷組成物、食用條等傾向以廣泛濃度之萃取物配製。於不同具體實例中,該萃取物之量與漱口水相似。
在一方面,加入以上討論之關於口腔用組成物治療量的萃取物組合物具有加入山竹萃取物主要成份的功效,諸如:各種氧葱酮及其衍生物,其在自上述由個別成份製得之組成物的重量百分比所給予者降低之治療量。因此,於一具體實例中,本發明提供口腔用組成物中包含0.01%重量比至5%重量比之治療量的氧葱酮之的潔牙劑。
於各種具體實例中,配製該組成物為含有至少一種保濕劑、至少一種磨料、載體,及有效量的萃取物組合物。於一具體實例中,該組成物含有0.01%至5%重量比之萃取物組合物,較佳是0.1%至2%重量比之萃取物組合物。於各種較佳具體實例中,除了0.1%至2%重量比之萃取物組合物之外,該牙膏或牙膠之組成物含有1%至70%重量比之至少一種保濕劑,及1%至70%重量比之至少一種磨料。
於各種具體實例中,該組成物未包含額外抗菌劑,雖然其使用為任意的。於案例中使用額外抗菌劑,該組成物可進一步包含抗菌劑,其選自氯化鯨蠟基吡啶鎓、多酚、酚類化合物、亞錫離子、鋅離子及其類似物之群組。
以任選其他組份配製,其包括但不限於:防齲齒劑、防牙結石或牙石控制劑、陰離子羧酸鹽聚合物、黏度改質劑、界面活性劑、香料、色素、信號劑(味道、顏色、光、熱、氣味及其他可標示有效或有益使用該組成物之信號劑)、治療口乾之藥劑等。
於各種具體實例中,該組成物包含口腔可接受之氟離子源,其作為一防齲齒劑。可存在一或多種此源。適宜之氟離子源包括:氟化物、一氟磷酸鹽及氟矽酸鹽類,以及胺氟化物,包括奧拉氟(olaflur)(N'-十八基三亞甲基二胺-N,N,N'-參(2-乙醇)-二氫氟化物(N'-octadecyltrimethylendiamine-N,N,N'-tris(2-ethanol)-dihydrofluoride))。
作為防齲齒劑,一或多種釋出氟之鹽類係視情況以提供總數100至20,000 ppm、200至5,000 ppm或500至2,500 ppm之氟離子存在。當氟化鈉為主要釋出氟之鹽存在時,該組成物中可存在舉例說明0.01%至5%、0.05%至1%或0.1%至0.5%重量比之氟化鈉的量。可使用其他防齲齒劑,諸如:精胺酸及精胺酸衍生物(例:乙基十二醯基精胺酸(ELAH))。
於此有用之酚類化合物舉例說明包括但不限於那些經Dewhirst(1980),Prostaglandins 20(2),209-222認定為具有抗發炎活性者,其視口腔可接受性之測定而定。抗菌酚類化合物之例子包括:4-烯丙基兒茶酚、對羥苯甲酸酯,包括:對羥苯甲酸苯甲酯、對羥苯甲酸丁酯、對羥苯甲酸乙酯、對羥苯甲酸甲酯及對羥苯甲酸丙酯,2-苄苯酚、丁基羥基甲氧苯、丁基化甲酚、辣椒素、香芹酚、木焦油醇、丁香酚、癒創木酚、鹵化雙酚類,包括:六氯芬(hexachlorophene)及溴氯芬,4-己間苯二酚、8-羥喹啉及其鹽類,柳酸酯,包括:柳酸薄荷酯、柳酸甲酯及柳酸苯酯,酚、鄰苯二酚、柳醯胺苯及百里酚,這些酚類化合物一般存在於上述一或多種天然萃取物中。
至少一種該酚類化合物視情況以總重之0.01%至10%重量比存在。舉例說明,於本發明之牙膏或膠潔牙劑或口腔漱劑中至少一種酚類化合物的總濃度可為0.01%至5%,例:0.1%至2%、0.2%至1%或0.25%至0.5%。
除了該天然萃取物之外,其他視情況可使用之抗菌劑包括但不限於銅(II)化合物,諸如:銅(II)氯化物、氟化物、硫酸鹽及氫氧化物,鋅離子源,諸如:醋酸鋅、檸檬酸鋅、葡萄糖酸鋅、甘胺酸鋅、氧化鋅、硫酸鋅及檸檬酸鋅鈉,酞酸及其鹽類,諸如:酞酸單鉀鎂、雙辛氫啶(hexetidine)、奧替尼啶(octenidine)、血根鹼、氯化苄烷銨、溴化度米芬(domiphen bromide),氯化烷基吡啶鎓(alkylpyridinium chlorides),諸如:氯化鯨蠟基吡啶鎓(CPC)(包括氯化鯨蠟基吡啶鎓與鋅及/或酶之結合物)、氯化十四烷基吡啶鎓及N-十四烷基-4-乙基氯化吡啶鎓,碘、磺醯胺類,雙二胍類(bisbiguanides),諸如:雙胍啶(alexidine)、氯己啶(chlorhexidine)及葡萄糖酸氯己啶(chlorhexidine digluconate),N-六氫吡啶基衍生物,諸如:地莫匹醇(delmopinol)及辛哌醇(octapinol),木蘭萃取物、葡萄籽萃取物、薄荷腦、香葉醇、檸檬油醛、桉樹油,抗生素,諸如:安滅菌(augmentin)、胺羥苄青黴素、四環黴素、去氧羥四環黴素(doxycycline)、二甲胺四環黴素(minocycline)、甲硝唑(metronidazole)、新黴素、康黴素及克林達黴素等。Gaffar等人之美國專利第5,776,435號提供有益抗菌劑之進一步說明表。若存在,這些額外之抗微生物劑存在一抗微生物之有效總量,通常為組成物的0.05%至10%,例如0.1%至3%重量比。
於另一具體實例中,該組成物包含一口腔可接受之防牙結石劑。可存在一或多種此藥劑。適宜之防牙結石劑包括但不限於磷酸鹽類及聚磷酸鹽類(例如:焦磷酸鹽類)、聚胺基丙烷磺酸(AMPS)、三水合檸檬酸鋅,多肽類,諸如:聚天門冬胺酸及聚麩胺酸,聚烯烴磺酸鹽、聚烯烴磷酸鹽,二膦酸鹽類,諸如:氮雜環烷-2,2-二膦酸鹽(例: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)及乙烷-1-胺基-1,1-二膦酸鹽,膦醯基烷羧酸及這些藥劑之鹽類,例如:其鹼金屬及銨鹽類,有益之無機磷酸鹽及聚磷酸鹽類,舉例說明包括:磷酸二氫鈉、磷酸氫二鈉及磷酸三鈉,三聚磷酸鈉、四聚磷酸鈉、焦磷酸一鈉、焦磷酸二鈉、焦磷酸三鈉及焦磷酸四鈉,焦磷酸二氫二鈉、三偏磷酸鈉、六偏磷酸鈉等,其中鈉可視情況替換為鉀或銨。其他有益之防牙結石劑包括陰離子聚羧酸酯聚合物。該陰離子聚羧酸酯聚合物於碳骨架上含有羧基,並包含丙烯酸、甲基丙烯酸酐及順丁烯二酐之聚合物或共聚物。非限定實例包括:聚乙烯甲基醚/順丁烯二酐(PVME/MA)共聚物,諸如那些來自紐澤西.委恩ISP(ISP,Wayne,NJ.)之GantrezTM
品牌者。其他有益之防牙結石劑包括鉗合劑,其包含羥基羧酸,諸如:檸檬酸、延胡索酸、蘋果酸、戊二酸及草酸,及其鹽類,以及胺基多羧酸,諸如:伸乙基二胺四乙酸(EDTA)。於組成物中視情況存在一或多種防牙結石劑,其呈防牙結石有效總量,通常為0.05%至50%,例如0.05%至25%或0.1%至15%重量比。
於各種具體實例中,該防牙結石系統包含三聚磷酸鈉(STPP)及焦磷酸四鈉(TSPP)之混合物。於各種具體實例中,TSPP對STPP之比例之範圍為1:2至1:4。於一較佳具體實例中,第防牙結石活性組份,TSPP係以1至2.5%存在,以及第二個防牙結石活性組份,STPP係以1至10%存在。
於一個具體實例中,該陰離子聚羧酸酯聚合物係以0.1%至5%存在。於另一具體實例中,該陰離子聚羧酸酯聚合物係以口腔照護組成物的0.5%至1.5%,最好1%存在。於根據本發明之一個具體實例中,防牙結石系統包含順丁烯二酐及甲基乙烯基醚之共聚物,例如:以上討論之Gantrez S-97產品。
於各種具體實例中,TSPP對STPP對合成陰離子聚羧酸酯之比例範圍為5:10:1至5:20:10(或1:4:2)。於一具體實例中,該口腔照護組成物之防牙結石系統包含呈1:7:1比例之TSPP、STPP及聚羧酸酯,諸如:順丁烯二酐及甲基乙烯基醚之共聚物。於一非限定具體實例中,該防牙結石系統實質上由以0.5%至2.5%存在之TSPP,以1%至10%存在之STPP,以及以0.5%至1.5%存在之順丁烯二酐及甲基乙烯基醚之共聚物。
於另一具體實例中,該組成物包含口腔可接受之亞錫離子源,其有用於,例如:幫助減少齒齦炎、牙菌斑、牙結石、齲齒或敏感。可存在一或多種該離子源。適宜之亞錫離子源包括但不限於亞錫氟化物、其他亞錫鹵化物,諸如:二水合氯化亞錫、焦磷酸亞錫、有機亞錫羧酸鹽類,諸如: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、丙二酸亞錫及檸檬酸亞錫、乙烯亞錫果綠定(stannous ethylene glyoxide)等。一或多種亞錫離子源係視情況且舉例說明地以組成物之0.01%至10%,例如0.1%至7%或1%至5%重量比之總量存在。
於另一具體實例中,該組成物包含口腔可接受之鋅離子源,其有用,例如作為抗微生物、防牙結石或口氣清新劑。可存在一或多個該離子源。適宜之鋅離子源包括但不限於醋酸鋅、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。一或多種鋅離子源係視情況且舉例說明地以組成物之0.05%至3%,例如0.1%至1%重量比之總量存在。
於另一具體實例中,該組成物包含口腔可接受之口氣清新劑。一或多種該等藥劑可以口氣清新有效總量存在。適宜之口氣清新劑包括但不限於鋅鹽類,諸如:葡萄糖酸鋅、檸檬酸鋅及氯酸鋅、α-紫羅蘭酮等。
於另一具體實例中,該組成物包含口腔可接受之抗牙菌斑劑,包括牙菌斑瓦解劑。一或多種該等藥劑可以抗牙菌斑有效總量存在。適宜之抗牙菌斑劑包括但不限於亞錫、銅、鎂及鍶鹽類,二甲基矽氧烷共聚醇(dimethicone copolyols),諸如:十六烷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,以及螯合劑,諸如:檸檬酸與酒石酸,及其鹼金屬鹽類。
於另一具體實例中,除了上述之迷迭香成份之外,該組成物包含口腔可接受之抗發炎劑。一或多種該等藥劑可以抗發炎有效總量的存在。適宜之抗發炎劑包括但不限於類固醇劑,諸如:氟西龍(flucinolone)及氫皮質酮,以及非類固醇劑(NSAIDs),諸如:酮咯酸(ketorolac)、氟比洛芬(flurbiprofen)、依布洛芬(ibuprofen)、萘普生(naproxen)、吲哚美辛(indomethacin)、待克菲(diclofenac)、依托度酸(etodolac)、吲哚美辛(indomethacin)、蘇林酸(sulindac)、托美丁(tolmetin)、酮洛芬(ketoprofen)、非諾洛芬(fenoprofen)、吡羅昔康(piroxicam)、萘丁美酮(nabumetone)、阿斯匹靈、二氟尼柳(diflunisal)、甲氯滅酸鈉(meclofenamate)、甲芬那酸(mefenamic acid)、羥基保泰松(oxyphenbutazone)及丁二苯吡唑二酮(phenylbutazone)。一或多種抗發炎劑可視情況以抗發炎有效量存在於組成物中。
本發明之組成物是情況含有其他組份,諸如:酶、維生素及抗黏著劑。可加入酶,諸如蛋白酶,以防染色及其他效果。維生素之非限定實例包括:維生素C、維生素E、維生素B5及葉酸。於各種具體實例中,該維生素具有抗氧化性質。抗黏著劑包括乙基十二醯基精胺酸(ELAH)、尼泊金乙酯(solbrol)、無花果蛋白酶、聚矽氧聚合物及衍生物,以及群數感應(quorum sensing)抑制劑。
任意包含於本發明組成物之有用載體係稀釋劑、磨料、碳酸氫鹽類、酸鹼值調節劑、界面活性劑、泡沫調節劑、增稠劑、黏度改質劑、保濕劑、甜味劑、香料及著色劑。相同或不同類別之一種載體原料,或者多種載體原料可視情況存在。應選擇與彼此或與該組成物之其他組份相容之載體。
水為較佳稀釋劑,且於某些組成物中,諸如:漱口水及美白液,通常附帶酒精,例:乙醇。漱口水組成物中水對酒精之重量比例通常為1:1至20:1,例如3:1至20:1,或4:1至10:1。於美白液中,水對酒精之重量比例可位於或低於上述範圍,例如1:10至2:1。
於一具體實例中,本發明之組成物包含至少一種磨料,有用於例如作為拋光劑。可使用任何口腔可接受之磨料,但應選擇磨料之形式、細度(顆粒尺寸)及量,以使牙齒琺瑯質於正常使用該組成物時不致過度磨損。適宜之磨料包括但不限於二氧化矽,例如:矽膠、水合矽石或沉澱矽石、礬土、不可溶磷酸鹽類、碳酸鈣、樹脂質磨料,諸如:尿素-甲醛縮合產物等之形式。可用作為磨料之不可溶磷酸鹽類係正磷酸鹽類、聚偏磷酸鹽類及焦磷酸鹽類。說明之實例係二水合正磷酸二鈣、焦磷酸鈣、β-焦磷酸鈣、磷酸三鈣、聚偏磷酸鈣及不可溶聚偏磷酸鈉。一或多種磨料係視情況以磨料有效總量,通常為組成物之5%至70%,例如10%至50%或15%至30%重量比存在。若存在,磨料之平均顆粒大小通常為0.1至30微米,例如1至20微米或5至15微米。
於進一步具體實例中,本發明之組成物包含至少一種碳酸氫鹽類,其有用於例如:因起泡並釋出二氧化碳而對牙齒及齒齦帶來“潔淨感”。可使用任何口腔可接受之碳酸氫鹽,其包括但不限於鹼金屬碳酸氫鹽,諸如:碳酸氫鈉及碳酸氫鉀、碳酸氫銨等。一或多種碳酸氫鹽類可視情況以組成物之0.1%至50%,例如1%至20%重量比的總量存在。
於更進一步具體實例中,本發明之組成物包含至少酸鹼值調節劑。此藥劑包括酸化劑以降低酸鹼值,鹼化劑以昇高酸鹼值,及緩衝劑以調控酸鹼值於所欲範圍內。例如:可包括選自酸化、鹼化及緩衝劑的一或多種化合物以調節酸鹼值於2至10,或於各種說明之具體實例2至8、3至9、4至8、5至7、6至10、7至9等。可使用任何口腔可接受之酸鹼值調節劑,其包括但不限於羧酸、磷酸及磺酸、酸之鹽類(例:檸檬酸一鈉、檸檬酸二鈉、蘋果酸一鈉等)、鹼金屬氫氧化物,諸如:氫氧化鈉,碳酸鹽類,諸如:碳酸鈉,碳酸氫鹽、二碳酸氫鹽類、硼酸鹽類、矽酸鹽類、磷酸鹽類(例:磷酸一鈉、磷酸三鈉、焦磷酸鹽類等)、咪唑等。一或多種酸鹼值調節劑係視情況以有效於維持該組成物於口腔可接受之酸鹼值範圍中之總量存在。
於更進一步具體實例中,本發明之組成物包含至少一種界面活性劑,其有用於例如使該組成物之其他成份相容,且因此提供增強之穩定性、以透過去污力幫助清潔牙齒表面,以及攪拌時提供泡沫,例如當以本發明之潔牙劑組成物刷牙時。可使用任何口腔可接受之界面活性劑,其大部份係陰離子性、非離子性或兩性。適宜之陰離子性界面活性劑包括但不限於C8-20
烷機硫酸鹽類之水溶性鹽類、C8-20
脂肪酸之磺酸化單甘油酯、肌胺酸鹽類、牛磺酸鹽類等。這些及其他類別之說明實例包括十二烷基硫酸鈉、椰子油單甘油酯磺酸鈉、十二烷基肌胺酸鈉、十二烷基乙磺酸鈉(sodium lauryl isoethionate)、月桂醇聚醚羧酸鈉(sodium laureth carboxylate)及十二烷基苯磺酸鈉。適宜之非離子性界面活性劑包括但不限於泊洛沙姆(poloxamer)、聚氧伸乙基去水山梨醇酯(polyoxyethylene sorbitan esters)、脂肪醇乙氧化物、烷基酚乙氧化物、三級胺氧化物、三級膦氧化物、二烷基亞碸等。適宜之兩性界面活性劑包括但不限於具有陰離子基,諸如:羧酸根、硫酸根、磺酸根、磷酸根或膦酸根之C8-20
脂肪族二級及三級胺的衍生物。一適宜例子為椰油醯胺丙基甜菜鹼。一或多種界面活性劑係視情況以組成物之0.01%至10%,例如0.05%至5%,或0.1%至2%重量比之總量存在。
於更進一步具體實例中,本發明之組成物包含至少一種泡沫調節劑,其有用於例如增加攪拌時該組成物產生之泡沫量、厚度或穩定性。可使用任何口腔可接受之泡沫調節劑,其包括但不限於聚乙二醇(PEGs),亦被稱為聚氧乙烯。適宜使用高分子量聚乙二醇,其包括那些具有平均分子量200,000至7,000,000,例如500,000至5,000,000,或1,000,000至2,500,000者。一或多種聚乙二醇係視情況以組成物之0.1%至10%,例如0.2%至5%,或0.25%至2%重量比之總量存在。
於更進一步具體實例中,本發明之組成物包含至少一種增稠劑,其有用於例如:賦予該組成物所欲之稠度及口感。可使用任何口腔可接受之增稠劑,包括但不限於卡波姆(carbomers),亦被稱為羧基乙烯基聚合物、鹿角菜膠,亦被稱為愛爾蘭藻,更特別稱為ι-鹿角菜膠(ι-鹿角菜膠)、纖維質聚合物,諸如:羥乙基纖維素、羧甲基纖維素(CMC),及其鹽類,例:羧甲基纖維素鈉、天然膠類,諸如:刺梧桐膠、三仙膠、阿拉伯膠,及黃蓍膠、膠態鎂鋁矽酸鹽、膠態二氧化矽等。一或多種增稠劑係視情況以組成物之0.01%至15%,例如0.1%至10%,或0.2%至5%重量比之總量存在。
於更進一步具體實例中,本發明之組成物包含至少一種黏度改質劑,其有用於例如抑制組份沉澱或分離,或於攪拌液態組成物時增進再分散性。可使用任何口腔可接受之黏度改質劑,包括但不限於礦物油、石臘脂、黏土及有機修飾黏土、矽石等。一或多種黏度改質劑係視請況以組成物之0.01%至10%,例如0.1%至5%重量比之總量存在。
於更進一步具體實例中,本發明之組成物包含至少一種保濕劑,其有用於例如:防止暴露於空氣時牙膏硬化。可使用任何口腔可接受之保濕劑,包括但不限於多元醇,諸如:甘油、山梨醇、木糖醇或低分子量之聚乙二醇。大部份保濕劑亦作為甜味劑之功能。一或多種保濕劑係視情況以組成物之1%至70%,例如1%至50%、2%至25%,或5%至15%重量比之總量存在。
於更進一步具體實例中,本發明之組成物包含至少一種甜味劑,其有用於例如:增加該組成物之風味。可使用任何口腔可接受之天然或人工甜味劑,包括但不限於葡萄糖、蔗糖、麥芽糖、糊精、乾燥轉化糖、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及玉米糖漿固體)、部份水解澱粉、氫化澱粉水解產物、山梨醇、甘露糖醇、木糖醇、麥芽糖醇、異麥芽糖、阿斯巴甜、紐甜(neotame)、糖精及其鹽類、以二肽為基底之加強甜味劑、賽克拉美人工甜味劑(cyclamates
)等。一或多種甜味劑係視情況以主要取決於所選之特定甜味劑,但通常以組成物之0.005%至5%重量比之總量存在。
於更進一步具體實例中,本發明之組成物包含至少一種香料,其有用於例如:增加該組成物之風味。可使用任何口腔可接受之天然或合成香料,包括但不限於香草醛、鼠尾草、馬鬱蘭、荷蘭芹油、綠薄荷油、肉桂油、冬青樹油(甲基柳酸酯)、薄荷油、丁香油、月桂油、大茴香油、桉樹油、柑橘油、果實油,及香精,包括那些取自:檸檬、柑橘、酸橙、葡萄柚、杏桃、香蕉、葡萄、蘋果、草莓、櫻桃、鳳梨等之香精,取自豆類及堅果之香味,諸如:咖啡、可可、可樂、花生、杏仁等,被吸附及包覆之香料等。於此之香料亦囊括提供口腔中香味及/或其他感官效果(包括:冰涼或溫暖效果)之組份。此組份舉例說明包括:薄荷腦、乙酸薄荷酯、乳酸薄荷酯、樟腦、桉樹油、桉樹醇、茴香腦、丁香酚、桂皮、覆盆子酮(oxanone)、α-紫羅蘭酮、丙烯基癒創木酚(propenyl guaiethol)、百里酚、沈香醇、苯甲醛、桂皮醛、N-乙基-對薄荷烷-3-羧胺、N,2,3-三甲基-2-異丙基丁醯胺、3-(1-甲氧基)-丙-1,2-二醇、桂皮醛甘油縮醛(CGA)、薄荷酮甘油縮醛(MGA)等。一或多種香料係視情況以組成物之0.01%至5%,例如0.1%至2.5%重量比之總量存在。
於更進一步具體實例中,本發明之組成物包含至少一種著色劑。此處之著色劑包括:色素、染料、沉澱染料,及賦予特定光澤或反光之藥劑,諸如:珍珠色劑。著色劑可提供一些功能,包括例如:提供牙齒表面上之白或亮色之塗層、用作為在該組成物有效接觸牙齒表面上之位置指示劑、及/或修飾該組成物之外觀,特別是顏色及/或不透明度以對消費者增加吸引力。可使用任何口腔可接受之著色劑,包括但不限於滑石、雲母、碳酸鎂、碳酸鈣、矽酸鎂、鎂鋁矽酸鹽、矽石、二氧化鈦、氧化鋅,紅、黃、棕及黑色氧化鐵、亞鐵氰化鐵銨、錳紫、群青、鈦雲母、氧氯化鉍等。一或多種著色劑係視情況以組成物之0.001%至20%,例如0.01%至10%,或0.1%至5%重量比之總量存在。
於另一具體實例中所提供口腔洗劑或漱口水之組成物,其含有水、一或多種如上述之香料、一或多種有機含氫化合物,以及如上述之有效抗菌量之抗菌組成物。於各種具體實例中,該口腔洗劑或漱口水組成物含有0.001%至5%重量比之含熊果酸及鼠尾草酸之植物的葉的酒精萃取物,諸如:藥鼠尾草(Rosmarinus. officinalis
)。於較佳之具體實例中,該組成物含有0.01%至1%重量比之迷迭香萃取物,例如:0.02%至0.5%重量比。該一或多種有機含氫化合物係口腔可接受之有機溶劑,諸如但不限於:乙醇及甘油。視情況地,該口腔洗劑及漱口水組成物含有一界面活性劑,以幫助散佈香料及抗菌組成物。
於各種具體實例中,本發明提供口香糖組成物,其包含膠基底及上述之有效量的萃取物之組合物。此外,口香糖配方通常含有一或多種可塑劑、至少一種甜味劑,及至少一種香料劑。
膠基底原料為本領域所熟知,並包括天然或合成之膠基底或其混合物。代表性之天然膠或彈性物包括:糖膠樹膠、天然橡膠、節路頓膠(jelutong)、巴拉塔樹膠、馬來樹膠、來開歐膠(leche caspi)、索馬膠(sorva)、古塔開膠(guttakay)、冠膠及佩里洛膠(perillo)。合成膠或彈性物包括:丁二烯-苯乙烯共聚物、聚異丁烯及異丁烯-異戊二烯共聚物,該膠基底以10至40%,及最好是20至35%之濃度併入口香糖產品中。
於其他具體實例中,該口腔用組成物包含一可食用口腔用條,其包含一或多種聚合的薄膜形成劑,及一有效量之上述萃取物之組合物。一或多種聚合的薄膜形成劑係選自由口腔可接受之聚合物,諸如:聚三葡萄糖、纖維素衍生物,及其他可溶性聚合物,包括那些本領域熟知之聚合物所組成之群組。
於各種具體實例中,該組成物有效對抗口腔細菌之組合,如在人工口腔抗牙菌斑之研究中所示。於各種具體實例中,與不含該抗菌組成物之負對照組比較,可見顯著降低牙菌斑發長。
於各種具體實例中,該組成物亦顯示抗氧化性質,例如:以經調配之潔牙劑進行之LPO-CC分析法證實,及/或於體外亦顯現臨床效果。例如:於較佳具體實例中,本發明組成物於修訂齒齦緣牙菌斑指數測定法(modified gingival margin plaque index determination)中顯現抗齒齦功效。已公開稱為MGMPI之該方法。包括有效量之迷迭香萃取物的組成物較負對照組呈現顯著改善。於其他具體實例中,本發明之組成物如於短期臨床研究中顯示亦有效對抗牙菌斑。
於各種具體實例中,本發明部份基於發現:當例如發現在山竹萃取物中之成份加入潔牙劑組成物中,該潔牙劑組成物之抗發炎效果增強。因此,本發明於各種具體實例中提供潔牙劑組成物,其含有萃取物之組合物,包括山竹萃取物,及除了山竹之外的天然萃取物。
本較佳具體實例現將參照以下非限定實例詳細說明。
使用以下組份製備牙膏配方:
當與不具天然萃取物組合物之常見牙膏配方相較,該上述牙膏配方將提供改良之抗菌及抗發炎性質。例如:該額外天然萃取物將為木蘭、迷迭香、山茶、桑色素、薑、烏龍茶、胡桃、竹葉花椒、香欖、黃葵、阿育吠陀印度草藥、大花苦油楝、非洲楝、山柑藤、葫蘆科(苦西瓜)、阿仙藥、阿拉伯金合歡、土牛膝、印度假苦楝、馬兜鈴、樟樹、錫蘭肉桂、鬱金、藍桉樹、囊葉榕、胡桃、長葉馬府油樹、香欖、九層塔、烏龍茶、荖花葉、蓽撥、胡椒、西南委陵菜、丁香、菊科植物(千日菊)、大果苔莓、秦椒,且當與不含天然萃取物及山竹的組合物之牙膏配方相較,該組成物將具有改良抗菌及抗發炎功效。
使用以下組份製備口腔洗劑配方:
當與不含天然萃取物的組合物之常見口腔洗劑配方相較,上述口腔洗劑配方將提供改良抗菌及抗發炎性質。
以上已參照說明實例描述本發明,但其可被理解為本發明非受限於所揭示之具體實例。本發明所屬技術領域中具有通常知識者閱讀本說明書所進行之變化及修正亦含括於本發明之範疇,其定義於於所附之申請專利範圍中。
Claims (6)
- 一種口腔用組成物,其包含:萃取物之組合物,該萃取物包含來自山竹(GARCINIA MANGOSTANA L. )之萃取物及來自山竹之萃取物之外的天然萃取物;及口腔可接受之載體;其中組成物包含0.01%至5%重量比之來自山竹之萃取物及0.01%至5%重量比之來自山竹之萃取物之外的天然萃取物且其中該來自山竹之萃取物之外的天然萃取物係一或多種天然萃取物,其選自由牛膝草、木蘭、越橘、迷迭香、山茶(Camellia )、桑色素、薑(zingiber officinale )、肉荳蔻(Myristica fragrans )、石榴(Punica granatum )、洋棗(Zizyphus Joazeiro)、柑橘(Jabara)、印度假苦楝(Azadirachta indica )、相思樹屬(Acacia )、烏龍茶(Oolong tea )、胡桃(Juglans regia )、竹葉花椒(Zanthoxylum alantum )、香欖(Mimusops elengi )、黃葵(Hibiscus abelmoschus )、阿育吠陀印度草藥(Ayurvedic )、大花苦油楝(Carapa procera )、非洲楝(Khaya senegalensis )、山柑藤(Salvadorapersica )、葫蘆科(Cucurbitaceae )(苦西瓜,Citrullus colocynthis )、阿仙藥(Acacia catechu )、阿拉伯金合歡(Acacia nilotica )、土牛膝(Achyrathes aspera )、印度假苦楝(Azadirachta indica )、馬兜鈴、(Aristolochia bracteolate )、樟樹(Cinnamomum camphora )、錫蘭肉桂(Cinnamomum verum )、藍桉樹(Eucalyptus globulus )、囊葉榕(Ficus bengalensis )、胡桃(Juglans regia )、長葉馬府油樹(Madhuca longifolia )、香欖(Mimusops elengi )、九層塔(Ocimum sanctum )、荖花葉(Piper betel leaves)、蓽撥(Piper longum )、胡椒(Piper nigrum )、西南委陵菜(Potentilla fulgens )、丁香(Syzygium aromaticum )、菊科植物(Spilanthes calva )、大果苔莓(Vaccinium macrocarpon )、秦椒(Zmthoxylum armatum )及其混合物的萃取物所組成之群組;其中來自山竹之萃取物包含0.01%至85%重量比之氧葱酮(xanthone)。
- 根據申請專利範圍第1項之組成物,包含0.1%至2%重量比的該萃取物之組合物。
- 根據申請專利範圍第1或2項之組成物,進一步包含額外抗菌劑,其選自:酚類化合物、亞錫離子、鋅離子及其混合物。
- 根據申請專利範圍第3項之組成物,其中該鋅離子係由一或多種含鋅之化合物提供,該含鋅之化合物係選自由醋酸鋅、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所組成之群組。
- 根據申請專利範圍第1或2項之組成物,其中該組成物進一步包含至少一種額外成份,其選 自由保濕劑、磨料、防齲齒劑、防牙結石或牙石控制劑、陰離子羧酸鹽聚合物、黏度改質劑、界面活性劑、香料、色素及其混合物所組成之群組。
- 根據申請專利範圍第1或2項之組成物,其中該組成物係潔牙劑,其呈選自由粉末、牙膏或牙膠;牙周膠;適合塗刷牙齒表面之液體;口香糖;不可溶、部份不可溶或非不可溶性薄膜或條;珠、薄片;手巾(wipe)或濕巾;移植物;漱口水、泡沫及牙線所組成之群組的形式。
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- 2010-12-01 JP JP2012542139A patent/JP2013512908A/ja active Pending
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- 2010-12-01 BR BR112012013469A patent/BR112012013469A2/pt not_active IP Right Cessation
- 2010-12-01 EP EP10787236A patent/EP2506933A1/en not_active Ceased
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CO6541605A2 (es) | 2012-10-16 |
CA2779906A1 (en) | 2011-06-09 |
RU2012127779A (ru) | 2014-01-20 |
PH12012500948A1 (en) | 2013-01-07 |
AR079303A1 (es) | 2012-01-18 |
TW201143844A (en) | 2011-12-16 |
CN102762259A (zh) | 2012-10-31 |
EP2506933A1 (en) | 2012-10-10 |
AU2010326136A1 (en) | 2012-05-31 |
BR112012013469A2 (pt) | 2016-05-17 |
US20120237456A1 (en) | 2012-09-20 |
WO2011068814A1 (en) | 2011-06-09 |
EP2689805A1 (en) | 2014-01-29 |
ZA201203512B (en) | 2014-10-29 |
MY152710A (en) | 2014-11-28 |
JP2013512908A (ja) | 2013-04-18 |
MX2012005908A (es) | 2012-06-13 |
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