TW201438750A - 口腔保健組成物 - Google Patents
口腔保健組成物 Download PDFInfo
- Publication number
- TW201438750A TW201438750A TW102144527A TW102144527A TW201438750A TW 201438750 A TW201438750 A TW 201438750A TW 102144527 A TW102144527 A TW 102144527A TW 102144527 A TW102144527 A TW 102144527A TW 201438750 A TW201438750 A TW 201438750A
- Authority
- TW
- Taiwan
- Prior art keywords
- zinc
- composition
- ascorbyl phosphate
- oral
- weight
- Prior art date
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- 239000000203 mixture Substances 0.000 title claims abstract description 172
- DBSABEYSGXPBTA-RXSVEWSESA-N (2r)-2-[(1s)-1,2-dihydroxyethyl]-3,4-dihydroxy-2h-furan-5-one;phosphoric acid Chemical compound OP(O)(O)=O.OC[C@H](O)[C@H]1OC(=O)C(O)=C1O DBSABEYSGXPBTA-RXSVEWSESA-N 0.000 claims abstract description 81
- 229940071097 ascorbyl phosphate Drugs 0.000 claims abstract description 81
- 229910052725 zinc Inorganic materials 0.000 claims abstract description 68
- 239000011701 zinc Substances 0.000 claims abstract description 67
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 claims abstract description 64
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 33
- 238000000034 method Methods 0.000 claims abstract description 27
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- 239000004599 antimicrobial Substances 0.000 claims abstract description 8
- XLOMVQKBTHCTTD-UHFFFAOYSA-N Zinc monoxide Chemical compound [Zn]=O XLOMVQKBTHCTTD-UHFFFAOYSA-N 0.000 claims description 56
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 claims description 28
- 239000000243 solution Substances 0.000 claims description 28
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- 239000003795 chemical substances by application Substances 0.000 claims description 26
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- 235000010323 ascorbic acid Nutrition 0.000 claims description 14
- PTFCDOFLOPIGGS-UHFFFAOYSA-N Zinc dication Chemical compound [Zn+2] PTFCDOFLOPIGGS-UHFFFAOYSA-N 0.000 claims description 13
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- LRXTYHSAJDENHV-UHFFFAOYSA-H zinc phosphate Chemical compound [Zn+2].[Zn+2].[Zn+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O LRXTYHSAJDENHV-UHFFFAOYSA-H 0.000 claims description 2
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- JZVZOOVZQIIUGY-UHFFFAOYSA-M sodium;tridecanoate Chemical compound [Na+].CCCCCCCCCCCCC([O-])=O JZVZOOVZQIIUGY-UHFFFAOYSA-M 0.000 description 1
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- 238000004885 tandem mass spectrometry Methods 0.000 description 1
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- 239000000606 toothpaste Substances 0.000 description 1
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- 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
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- 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
- RYFMWSXOAZQYPI-UHFFFAOYSA-K trisodium phosphate Chemical compound [Na+].[Na+].[Na+].[O-]P([O-])([O-])=O RYFMWSXOAZQYPI-UHFFFAOYSA-K 0.000 description 1
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- 108010050327 trypticase-soy broth Proteins 0.000 description 1
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- 241001446247 uncultured actinomycete Species 0.000 description 1
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- 229940056904 zinc ascorbate Drugs 0.000 description 1
- 229960001296 zinc oxide Drugs 0.000 description 1
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- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
- A61K8/58—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing atoms other than carbon, hydrogen, halogen, oxygen, nitrogen, sulfur or phosphorus
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- A—HUMAN NECESSITIES
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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
- A61K8/19—Cosmetics or similar toiletry preparations characterised by the composition containing inorganic ingredients
- A61K8/27—Zinc; Compounds thereof
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- A—HUMAN NECESSITIES
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K33/00—Medicinal preparations containing inorganic active ingredients
- A61K33/24—Heavy metals; Compounds thereof
- A61K33/30—Zinc; Compounds thereof
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- A—HUMAN NECESSITIES
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
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- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
- A61K8/55—Phosphorus compounds
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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
- A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
- A61K8/67—Vitamins
- A61K8/676—Ascorbic acid, i.e. vitamin C
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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
- 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
- A61K2800/40—Chemical, physico-chemical or functional or structural properties of particular ingredients
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Landscapes
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- Veterinary Medicine (AREA)
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- Inorganic Chemistry (AREA)
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- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
本發明係提供口腔保健組成物,其包含口腔可接受水性載劑及抗微生物組成份,其中,該抗微生物組成份包含抗壞血酸磷酸鋅,及使用本文中所揭示之口腔保健組成物用於治療或預防口腔之疾病或障礙之方法。
Description
本發明係提供口腔保健組成物,其包含口腔可接受水性載劑及抗微生物組成份,其中,該抗微生物組成份包含抗壞血酸磷酸鋅,及使用本文中所揭示之口腔保健組成物用於治療或預防口腔之疾病或障礙之方法。
口腔細菌導致多種口腔之疾病或障礙,包括齲齒、牙周疾病如牙齦炎及牙周炎、牙菌斑、口腔惡臭及口臭係為已知。口腔細菌及彼等引起之口腔組織慢性發炎業已涉及多種全身性疾病,包括心血管疾病。
因此,期望提供含抗細菌劑之口腔保健組成物。許多先前已使用之抗細菌劑具有不等程度之成功。鋅化合物類,特別氧化鋅已顯示大有可為。除了其等之抗微生物特性,鋅化合物可對抗牙菌斑,防止結石形成且減少口腔惡臭。鋅化合物亦已用於治療及預防其他口腔之疾病或症狀,如膿漏及牙齒敏感症。
儘管有此等大有可為之特性,於口腔保健組成物上使用鋅仍有其限制。許多抗微生物之鋅化合物,且特別氧化鋅,苦於不良之水溶性。此限制先前技術之鋅化合物於配製物中合併之範圍。不良之溶解性於製造口腔保健配製物中可導致難以達成均勻的產物。因此,於此方面技藝中需要改良溶解性之鋅化合物。
通常想要提供具有高效力之抗微生物組成份。效力可藉測定最小抑制濃度(MIC)來定量。該MIC為產生殺生物或生物抑制效力所需之最小濃度。業已報導鋅具有不想要之感官特性且可引起口腔刺激,而仍需要此方面技藝中具有改良效力之鋅化合物,其允許降低所使用之鋅劑量,同時保持鋅之有用功能。
本發明之適用性的其他領域可由下文中所提供之詳細說明變得顯而易見。應瞭解當指明本發明之較佳具體例時,該詳細說明及特定實例意欲用於闡明之目的而已且並非意欲用來限制本發明之範圍。
本發明之目的係提供口腔保健組成物,其含有於水介質中具改良溶解性之鋅化合物及增強之抗微生物效能。
於第一方面中,本發明係提供含口腔可接受水性載劑及抗微生物組成份之口腔保健組成物,其中,該抗微生物組成份包含抗壞血酸磷酸鋅。
任意地,該抗壞血酸磷酸鋅係選自於下列之群組,包括:抗壞血酸磷鋅(II)(ascorbylphosphato zinc(II))、抗壞血酸磷氯鋅(II)(ascorbylphosphatochlorido zinc(II))、抗壞血酸磷羥鋅(II)(ascorbylphosphatohydroxo zinc(II)),及其混合物。
任意地,該抗壞血酸磷酸鋅係於該組成物中以至少3.0mM之濃度。
任意地,該組成物之pH係於5.5至10之範圍,較佳於6至8。
任意地,該組成物進一步包含至少一種組份選自於下列之群組,包括:表面活化劑、減敏感劑、美白劑、齒垢控制劑、磨蝕劑、黏合
劑、增稠劑、去垢劑、黏附劑、泡沫調製劑、pH調節劑、口感劑、甜味劑、增香劑、著色劑、防腐劑、濕潤劑、氟化物離子來源及其組合物。
任意地,該組成物係為潔牙劑形式。
任意地,該組成物係為漱口劑形式。
任意地,該組成物係於人類或動物個體中治療或預防口腔之疾病或障礙之方法中使用,該方法包含施用該組成物至該個體之口腔。
於第二方面中,本發明係提供抗壞血酸磷酸鋅使用於口腔保健組成物中作為抗微生物組成份。
於第三方面中,本發明係提供於人類或動物個體中治療或預防口腔之疾病或障礙之方法,該方法包含施用本發明之組成物至該個體之口腔。
於第四方面中,本發明係提供口腔保健組具,其包括含抗壞血酸磷酸鋅之口腔保健組成物。
於第五方面中,本發明係提供製造口腔保健組成物之方法,其包含製備氧化鋅之懸浮液;製備抗壞血酸磷酸酯之溶液;混合該氧化鋅懸浮液及該抗壞血酸磷酸酯溶液;且將該氧化鋅與抗壞血酸磷酸酯進行反應以便形成複合物。
業已令人驚奇地發現,抗壞血酸磷酸鋅具有明顯更高之溶解性及抗微生物效力,與先前技術之抗微生物組成份相較時。
下列較佳具體例(類)之說明僅係性質上示範且不以任何方式意欲限制本發明,其之應用,或用途。
本發明之口腔保健組成物包括功能如抗微生物組成份之抗壞血酸磷酸鋅,及口腔可接受之水性載劑。已令人驚奇地發現抗壞血酸磷酸鋅,比習用於口腔保健組成物中之鋅化合物,更溶於水介質中。改良之溶解性通常係想要的,因為其允許調配師更大的彈性以及降低製造困難。
亦已發現抗壞血酸磷酸鋅具有非常好的促進口腔健康之抗微生物特性及抗氧化特性。此可允許降低口腔保健組成物中之鋅量,因而減少消費者可感知之鋅的負面感官性,同時仍傳送其令人滿意之功能。亦期望以商業立場來減少活性組成份於口腔保健組成物中之數量,且因而降低成本。
“抗壞血酸磷酸鋅”一詞通常係指包含鋅中心及至少一種抗壞血酸磷酸酯配體之任何複合物。
抗壞血酸磷酸鋅可任意包含一種或多種附加之配體。該附加配體之性質並未特別限制,只要該產生之複合物適當於口腔保健組成物中使用。較佳附加配體之實例包括羥(hydroxo)及氯化物配體、鹵化物(例如,氟、溴、碘)及有機陰離子(例如,醋酸鹽、甲酸鹽及硝酸鹽)。
較佳為,該抗壞血酸磷酸鋅為可由,或可藉由下列之方法得到之抗壞血酸磷酸鋅,該方法為:a.製備氧化鋅之水懸浮液;b.製備抗壞血酸磷酸酯之水溶液;c.混合該氧化鋅懸浮液及該抗壞血酸磷酸酯溶液;d.任意調整該混合物之pH,較佳其中該溶液之pH係調整至pH 7及/或較佳其中係使用酸如氫氯酸來調整該溶液之pH;及e.最好讓該產生之溶液靜置,直到獲得澄清之溶液。
並非希望藉由特別之理論來束縛,一般認為如上之方法係產生鋅複合物之混合物。當以LC-MS-MS分析時,該複合物之混合物主要包含抗壞血酸磷鋅(II)、抗壞血酸磷氯鋅(II)及抗壞血酸磷羥鋅(II)。其他不重要之組份可能存在。
較佳為,該抗壞血酸磷酸鋅為選自於下列群組之抗壞血酸磷酸鋅,其包括:抗壞血酸磷鋅(II)、抗壞血酸磷氯鋅(II)、抗壞血酸磷羥鋅(II)及其混合物。
更佳為,該抗壞血酸磷酸鋅為抗壞血酸磷鋅(II)、抗壞血酸
磷氯鋅(II)及抗壞血酸磷羥鋅(II)之混合物。該三種組成份之二種對其他者之比率為1:6至6:1。較佳為,抗壞血酸磷鋅(II):抗壞血酸磷氯鋅(II):抗壞血酸磷羥鋅(II)之比率為3:5:1。
口腔可接受之水性載劑為包括水及口腔保健組份之任何混合物。該口腔保健組份之性質並未特別限制。該口腔保健組份可,例如,選自於下列之群組,包括:表面活化劑、減敏感劑、美白劑、齒垢控制劑、磨蝕劑、黏合劑、增稠劑、去垢劑、黏附劑、泡沫調製劑、pH調節劑、口感劑、甜味劑、香味劑、著色劑、防腐劑、濕潤劑、氟化物離子來源及其組合物。較佳為,該口腔可接受水性載劑係包含氟化物離子來源及/或濕潤劑。較佳為,該抗壞血酸磷酸鋅係溶解於該口腔可接受水性載劑中。該口腔可接受水性載劑可任意包含一種或多種共溶劑。該共溶劑可為,例如,乙醇。此外,該共溶劑可為丙三醇或丙二醇。
本文中所說明之口腔保健組成物可配製成此方面技藝中已知之任何輸送形式。例如,可將該組成物配製成漱口劑、糊膏、凝膠、錠片(可溶或可咀嚼)、噴霧、樹膠或薄膜(全部或部份可溶或不可溶)。該組成物可含有任何習用賦形劑或載體。該賦形劑當然係依所選擇之劑量形式或劑量裝置而變化。
較佳為,該口腔保健組成物可配製成潔牙劑。潔牙劑之實例包括牙膏及凝膠。較佳為,該潔牙劑係經配製於刷牙中使用。當配製成潔牙劑時,該組成物宜包含氟或氟化物化合物。
或者,本發明之組成物可配製成漱口劑。漱口劑典型地包含一種或多種口腔保健組成份之水溶液或酒精溶液。
典型地,該口腔保健組成物包含至少有效數量之抗壞血酸磷酸鋅。有效數量為抑制至少一種微生物生長,或其提供殺生物效益之數量。該微生物典型地為桿菌屬(bacterium)。較佳為,該微生物為口腔中所發現之微生物。更佳為,該微生物為口腔中所發現之致病性微生物。
較佳為,該口腔保健組成物包含濃度至少3.0mM、或至少3.5mM、或至少4.0mM、或至少4.5mM、或至少5.0mM、或至少6.0mM之抗壞血酸磷酸鋅。
典型地,該口腔保健組成物包含低於該抗壞血酸磷酸鋅之最大安全濃度。該最大安全濃度為當該口腔保健組成物投遞於個體時,可合併於該口腔保健組成物中不會對個體造成永久性傷害之最高濃度。較佳為,該口腔保健組成物含有低於可被典型消費者所感知之抗壞血酸磷酸鋅的濃度。較佳為,該抗壞血酸磷酸鋅之濃度於該組成物中不會超過抗壞血酸磷酸鋅之熱力溶解度。
該口腔保健組成物可包含濃度不大於50mM、或10mM、或5mM、或3mM之抗壞血酸磷酸鋅。
較佳為,抗壞血酸磷酸鋅可於該組成物中以範圍於3mM至5mM之濃度。更佳為,抗壞血酸磷酸鋅係以範圍於3mM至4mM之濃度存在於該組成物中。任意地,抗壞血酸磷酸鋅可於該組成物中以3mM、或3.5mM、或4.0mM、或4.5mM、或5.0mM、或5.5mM、或6.0mM之濃度。
應瞭解,抗壞血酸磷酸鋅於該組成物中之濃度會依該組成物之性質而變化。典型地,該組成物之pH係於pH 2至pH 10之範圍。任意地,該組成物之pH係於pH 2至pH 8,或pH 3至pH 8,或pH 4至pH 8,或pH 5至pH 7,或pH 6至pH 10或pH 7至pH 9之範圍。抗壞血酸磷酸鋅之濃度於潔牙劑中之較佳範圍係於0.05至4%,按該組成物之重量。抗壞血酸磷酸鋅之濃度於漱口劑中之較佳範圍係於0.05至2%,按該組成物之重量。
該組成物可具有於口腔保健組成物中使用可接受之任何pH。較佳者,該組成物之pH係於pH 5.5至pH 10之範圍。更佳者,該組成物之pH係於pH 6至pH 8之範圍。還有更佳者,該pH係於pH 6.5至pH 7.4
之範圍。最佳為,該組成物之pH為pH 7。
本發明之組成物可包含一種或多種附加之口腔保健組成份。該一種或多種附加之口腔保健組成份可任意選自於下列之群組,包括:表面活化劑、減敏感劑、美白劑、齒垢控制劑、磨蝕劑、黏合劑、增稠劑、去垢劑、黏附劑、泡沫調製劑、pH調節劑、口感劑、甜味劑、香味劑、著色劑、防腐劑、濕潤劑、氟化物離子來源及其組合物。
表面活化劑可使用於本發明之口腔保健組成物中以提供發泡、味道、香味、質地及口感特性至該組成物,且特別使該組成物成為化妝品更可接受者。適當之表面活化劑包括但非侷限於,C8-20烷基硫酸酯之水溶性鹽、C8-20脂肪酸之磺化甘油一酸酯、肌胺酸鹽、牛磺酸鹽、月桂基硫酸鈉、椰基甘油一酸酯磺酸鈉、月桂基肌胺酸鈉、月桂基異乙烯磺酸鈉、第十二烷基羧酸鈉及十二烷基苯磺酸鈉,及椰基醯胺基丙基甜菜鹼。較佳為,該表面活化劑包含月桂基硫酸鈉(SLS)。
本發明之組成物係任意合併一種或多種減敏感劑,例如,鉀鹽如硝酸鉀、碳酸氫鉀、氯化鉀、檸檬酸鉀,及草酸鉀;番椒辣素;丁子香酚;鍶鹽;鋅鹽;氯化物鹽及其組合物。此等試劑可以有效之數量添加,例如,根據該組成物之總重量,以於範圍由1重量%至20重量%按重量之數量,依所選擇之試劑而定。本發明之組成物當施用於牙齒時亦可藉阻斷牙本質小管用來治療敏感症。
本發明之組成物可任意包括牙齒美白或牙齒漂白劑。適當之美白及漂白劑包括,過氧化物、金屬亞氯酸鹽、過硫酸鹽。過氧化物包括氫過氧化物、過氧化氫、鹼金屬及鹼土金屬之過氧化物、有機過氧化合物、過氧酸,及其混合物。鹼金屬及鹼土金屬之過氧化物包括過氧化鋰、過氧化鉀、過氧化鈉、過氧化鎂、過氧化鈣、過氧化鋇,及其混合物。其他過氧化物包括過硼酸鹽、脲過氧化物,及其混合物。適當之金屬亞氯酸鹽可包括亞氯酸鈣、亞氯酸鋇、亞氯酸鎂、亞氯酸鋰、亞氯酸鈉,及亞氯酸鉀。
此等試劑可以有效之數量添加,例如,根據該組成物之總重量,以於範圍由1重量%至20重量%按重量之數量,依所選擇之試劑而定。
本發明之口腔保健組成物可任意地包括齒垢控制劑,如焦磷酸鹽包括二鹼或四鹼金屬焦磷酸鹽,如Na4P2O7、K4P2O7、Na2K2P2O7、Na2H2P2O7及K2H2P2O7,三聚磷酸鈉,長鏈聚磷酸鹽如六偏磷酸鈉及環狀磷酸鹽如三偏磷酸鈉。
本發明之組成物亦可包括磨蝕劑。該磨蝕劑可為矽石磨蝕劑,如具有平均粒子大小多至約20微米之沉澱或水合矽石,如矽歐頓(Zeodent)105及矽歐頓114,由J.M.胡柏化學品部門銷售(J.M.Huber Chemicals Division,Havre de Grace,Md.21078),或塞洛頓(Sylodent)783,由W.R.葛蕾絲公司大維森化學部門銷售(Davison Chemical Division of W.R.Grace & Company)。其他有用的潔牙劑磨蝕劑包括偏磷酸鈉、偏磷酸鉀、磷酸三鈣、二水合之磷酸二鈣、矽酸鋁、煅燒礬土、膨潤土或其他矽質材料,或其組合物。
其他可能之磨蝕材料包括具有油吸收值小於約100cc/100克矽石且任意於範圍由約45cc/100克至小於70cc/100克矽石之矽膠及沉澱無定形矽石。此等矽石為膠體粒子,當以5%按淤漿重量測量時,其具有平均粒子大小於範圍由3微米至12微米,且任意於5至10微米,及pH於範圍由4至10,任意於6至9。
該磨蝕劑可根據該組成物之重量任意地以於由15至35重量%,根據該組成物之重量任意於範圍20至30重量%之數量存在。
本發明之組成物可含有黏合劑。可採用任何習用之黏合劑。適當之試劑包括海洋膠體、羧基乙烯基聚合物、角叉菜、澱粉、纖維質聚合物如羥基乙基纖維素、羧基甲基纖維素(卡美洛斯(carmellose))、羥基丙基甲基纖維素及其鹽(例如,卡美洛斯鈉(carmellose sodium))、天然樹膠如刺梧桐、黃原、阿拉伯膠及西黃蓍膠、聚甲殼糖、膠態矽酸鋁鎂,及膠態矽石。
較佳為,若該組成物為潔牙劑,則黏合劑係按該組成物之重量以於範圍0.5%至5%之數量存在於該組成物中。
適用於本發明組成物中之增稠劑包括天然及合成之樹膠及膠體。適當之增稠劑包括天然存在之聚合物如角叉菜、黃原膠,不同分子量之聚乙二醇以商品名保粒歐(Polyox)出售者,及聚乙烯吡咯烷酮。可相容之無機增稠劑包括功能如增稠劑之無定形矽石化合物,及包括膠態矽石化合物,其可得自於商業名稱為Cab-o-sil由卡波特公司(Cabot Corporation)製造及由里納皮化學公司(Lenape Chemical,Bound Brook,N.J.)分配者;矽歐頓(Zeodent)165,由J.M.胡柏化學品部門銷售(J.M.Huber Chemicals Division,Havre de Grace,Md.21078);及塞洛頓(Sylodent)15,其可得自於W.R.葛蕾絲公司大維森化學部門(Davison Chemical Division of W.R.Grace Corporation,Baltimore,Md.21203)。其他無機增稠劑包括天然及合成黏土,如水輝石黏土、矽酸鋰鎂(拉膨奈(laponite))及矽酸鋁鎂(威膠(Veegum))。
本發明之口腔保健組成物可任意包含一種或多種黏附劑。該黏附劑可為聚合黏附材料。該聚合黏附材料可為任何已知或於此方面技藝中將發展附著於哺乳類牙齒之表面及/或於亦可於牙齒表面上呈現之異質生物膜。附著係可藉由任何方式,如離子相互作用、凡得瓦爾力、疏水-親水之相互作用等發生。該黏附材料可為,例如,黏附於牙齒表面之任何均聚物或共聚物(下文中統稱為"聚合物")。此等聚合物可包括纖維素聚合物,例如,一種或多種羥基烷基纖維素聚合物,如羥基丙基甲基纖維素(HPMC)、羥基乙基丙基纖維素(HEPC)、羥基丁基甲基纖維素(HBMC)、羧基甲基纖維素(CMC)。
較佳為,該聚合黏附材料包含至少一種纖維素物質,例如羧基甲基纖維素鈉。
該聚合黏附材料可替代地或附加地包括聚(乙烯化氧)聚合物(如來自於道氏化學公司之保粒歐(POLYOX))、線性PVP及交聯PVP、
PEG/PPG共聚物(如BASF公司之Pluracare L1220)、乙烯化氧(EO)-丙烯化氧(PO)嵌段共聚物(如可得自於BASF公司以商標普朗尼(pluronic)銷售之聚合物)、酯膠、蟲膠、壓合矽酮膠黏劑(如來自於道康寧公司之BioPSA)、甲基丙烯酸酯,或其混合物。於一個具體例中,共聚物包含(PVM/MA)。任意地,該共聚物可選自於下列之群組,包括:聚(甲基乙烯基醚/順式丁烯二酸酐),或聚(甲基乙烯基醚/順式丁烯二酸),或聚(甲基乙烯基醚/順式丁烯二酸)半酯,或聚(甲基乙烯基醚/順式丁烯二酸)混合的鹽。
可使用任何分子量之聚合物,包括,例如分子量50,000至500,000、500,000至2,500,000或2,500,000至10,000,000(以數值平均或重量平均來計算)。
本發明之口腔保健組成物亦可包括泡沫調製劑。泡沫調製劑典型地會增加所產生之泡沫的數量,例如,當使用本發明之組成物刷口腔時。
增加泡沫數量之泡沫調製劑的闡明性實例包括,但非侷限於聚氧化乙烯及特定聚合物包括,但非侷限於,藻朊酸鹽聚合物。
該聚氧化乙烯可增加由本發明之口腔保健載體組份所生成之泡沫的數量及泡沫的厚度。聚氧化乙烯通常亦稱為聚乙二醇("PEG")或聚乙烯化氧。適用於本發明之聚氧化乙烯係具有分子量200,000至7,000,000,且較佳600,000至2,000,000且更佳800,000至1,000,000。
該聚氧化乙烯可按本發明口腔保健組成物之口腔保健載體組份之重量,以1%至90%之數量存在,於一個具體例中5%至50%且於另一個具體例中10%至20%。於該口腔保健組成物中之起泡劑的劑量(亦即,單劑量)為0.01至0.9%按重量,0.05至0.5%按重量,且於另一個具體例中為0.1至0.2%按重量。
任意地,本發明之組成物包含至少一種pH調節劑。此等試劑包括酸化劑以降低pH,鹼化劑以提升pH,及緩衝劑以控制pH於想要之
範圍內。例如,可包括一種或多種化合物選自於酸化、鹼化及緩衝劑以提供2至10之pH,或於多種闡明性具體例中,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pH調節劑,包括但非侷限於,羧酸、磷酸及磺酸、酸式鹽(例如,檸檬酸一鈉、檸檬酸二鈉、蘋果酸一鈉等)、鹼金屬氫氧化物如氫氧化鈉、碳酸鹽如碳酸鈉、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)、咪唑及類似物。一種或多種pH調節劑係任意地以有效維持該組成物於口腔可接受之pH範圍中之總數量存在。
可使用於本文中之口感劑包括於使用該組成物時,賦予所要之質地或其他感覺之物質。此等試劑包括碳酸氫鹽,由於二氧化碳起泡及釋放,其可賦予牙齒及牙齦“乾淨的感覺。可使用任何口腔可接受之碳酸氫鹽,包括但非侷限於,鹼金屬碳酸氫鹽如碳酸氫鈉及碳酸氫鉀、碳酸氫銨,及其混合物。一種或多種碳酸氫鹽係任意地以於範圍0.1%至50%按重量之總數量存在,例如5%至20%。
本發明之組成物可任意包含甜味劑。可使用於本發明之組成物中之甜味劑包括人工甜味劑,如糖精、醋磺內酯(acesulfame)、紐甜(neotame)、環己基磺醯胺酸鹽(cyclamate)或蔗糖素(sucralose);天然高強度甜味劑,如索馬甜(thaumatin)、甜菊糖或甘草甜素(glycyrrhizin);或蔗糖醇,如山梨糖醇、木糖醇、麥芽糖醇或甘露糖醇。此等可根據該組成物之重量,以於範圍0重量%至0.2重量%,任意於0.005重量%至0.1重量%之數量存在。
本發明之組成物可任意地包含香味劑。可使用於本發明之組成物中之香味劑包括精油以及多種香味醛、酯、醇,及類似物質。精油之實例包括綠薄荷、薄荷、茴香子、鹿蹄草、黃樟、丁香、鼠尾草、桉樹、黑角蘭、肉桂、檸檬、萊姆、葡萄柚,及柳橙之油。亦有用者為此等化學品如醇、香芹酮,及茴香腦。此等中,最常採用者為薄荷及綠薄荷的油。
該香味劑可以於範圍0.1至5重量%且典型地0.5至1.5重量%之濃度合併於該口腔保健組成物中。
若該口腔保健組成物係配製成漱口劑,則香味劑較佳係根據該組成物之重量,以於範圍0重量%至0.5重量%,任意於0.03重量%至0.3重量%之數量使用。
若該口腔保健組成物係配製成潔牙劑或牙膠,則香味劑較佳係根據該組成物之重量,以於範圍0.1至5重量%,任意於0.5至1.5重量%之數量存在於該組成物中。
本發明之組成物可包含至少一種著色劑。於本文中著色劑係包括顏料、染料、色澱及增添特別光澤或反射性之試劑如珠光劑。可使用任何口腔可接受之著色劑,包括但非侷限於,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、褐及黑色氧化鐵、氰亞鐵酸鐵銨(ferric ammonium ferrocyanide)、錳紫、群青、鈦酸雲母、氯氧化鉍,及類似物。一種或多種著色劑係任意地按該組成物之總重量,以於範圍由0.001重量%至20重量%之數量存在,例如,由0.01重量%至10重量%,或由0.1重量%至5重量%。
防腐劑,如氯己酊(chlorhexidine)、三氯生(triclosan)、季銨化合物(如苯烷銨氯化物(benzalkonium chloride))或對羥苯甲酸酯類,如甲基或丙基對羥苯甲酸酯可使用於該組成物中。該防腐劑之數量典型地係根據該組成物之重量於範圍由0至0.5重量%,任意於0.05至0.1重量%。
本發明之組成物可任意地包含濕潤劑。可使用任何口腔可接受之濕潤劑,包括但非侷限於,多元醇如丙三醇、山梨糖醇、木糖醇或低分子量PEGs。大多數濕潤劑亦功能如甜味劑。一種或多種濕潤劑係任意地按該組成物之總重量,以於範圍由1重量%至70重量%之總數量存在,例如,由1重量%至50重量%,由2重量%至25重量%,或由5重量%至15重量%。
較佳為,該組成物包含氟化物離子來源。氟化物離子來源包括,但非侷限於:氟化亞錫、氟化鈉、氟化鉀、單氟磷酸鉀、單氟磷酸鈉、單氟磷酸銨、氟矽酸鈉、氟矽酸銨、氟化胺如歐拉氟(olaflur)(N'-十八基三亞甲基二胺-N,N,N'-三(2-乙醇)-二氫氟化物)、氟化銨,及其組合物。任意地,該氟化物離子來源係包括氟化亞錫、氟化鈉、氟化銨、單氟磷酸鈉,以及其混合物。較佳為,本發明之口腔保健組成物亦可含有氟化物離子之來源或提供氟之組成份,以足夠供應50至約5000ppm氟化物離子,例如,由100至約1000,由200至500,或250ppm氟化物離子之數量。氟化物離子來源可,以於範圍0.001重量%至10重量%之含量添加至本發明之組成物,例如,由0.003重量%至5重量%,0.01重量%至1重量,或0.05重量%。然而,應理解用來提供適當氟化物離子含量之氟化物鹽的重量將明顯地根據該鹽中之平衡離子的重量而變化,且精於此方面技藝之人士可容易地測定此等數量。較佳之氟化物鹽可為氟化鈉。
亦提供於人類或動物個體中治療或預防口腔之疾病或障礙之方法,該方法包含施用含抗壞血酸磷酸鋅之口腔保健組成物至該個體之口腔。
較佳者,該個體為人類,或伴侶動物,如貓、狗或馬。最佳者,該個體為人類。該組成物可藉由此方面技藝中已知之任何適當方法來施用。可使用已知於此方面技藝中之任何適當技術,施用該組成物至個體之口腔。該技術可依該組成物之性質而變化。例如,若該組成物為潔牙劑,較佳係藉刷牙且更佳係藉刷牙達約2分鐘來施用。
任何適當之劑量攝取法可與本發明之方法合併使用。例如,可將該組成物以一天一次,一天兩次,或更經常地施用至個體之口腔。較佳係,該組成物以一天兩次施用至個體之口腔。該個體可用該組成物處理達至少一天、至少一個月、至少6個月、至少一年,或達一生之期間。
可使用本發明之方法及組成物來治療或預防多種口腔之疾
病及障礙。任意地,本發明之方法及組成物可用來治療或預防慢性疾病或障礙。該疾病或障礙可為齲齒。該疾病或障礙可為牙周疾病,或牙周發炎。該牙周疾病可為牙齦炎。該疾病或障礙可為口臭。
該疾病或障礙可為牙齒敏感症。若該疾病或障礙為牙齒敏感症,該組成物宜包含附加之口腔保健組成份,其為減敏感劑。該疾病或障礙可為齒垢堆積及/或結石形成。若該疾病或障礙為齒垢堆積及/或結石形成,該組成物宜包含附加之口腔保健組成份,其為齒垢控制劑及/或磨蝕劑。
任意地,該疾病或障礙可為牙齒變色。若該疾病或障礙為牙齒變色,該組成物宜包含附加之口腔保健組成份,其為牙齒美白劑。
於進一步之觀點中,本發明係提供含口腔保健組成物之口腔保健組具,該組成物包含抗壞血酸磷酸鋅。本發明之組具宜包含本發明之組成物裝置於適當包裝中。本發明之組具可任意包含適當之塗抹器,如牙刷或類似物。本發明之組具可任意包含用於測量適當給藥該組成物之裝置。若該組成物為漱口劑,用於測量及適當給藥該組成物之裝置宜包含具刻度之測量容器。
於進一步之觀點中,本發明係提供用於製造口腔保健組成物之方法。該方法包含產生抗壞血酸磷酸鋅。然後可使用已知於此方面之技藝中之任何適當方法,將該抗壞血酸磷酸鋅合併於口腔保健組成物中。
較佳者,產生抗壞血酸磷酸鋅之步驟包括:a.製備懸浮液,較佳為氧化鋅之水懸浮液;b.製備溶液,較佳為抗壞血酸磷酸酯之水溶液;c.混合該氧化鋅懸浮液及該抗壞血酸磷酸酯溶液;d.任意調整該混合物之pH,其中該溶液之pH較佳係至pH 7及/或其中該溶液之pH較佳使用氫氯酸來調整;及e.該氧化鋅與抗壞血酸磷酸酯進行反應,較佳係讓該混合物靜置直到獲得澄清溶液。
任意地,可使用液體色層分離法來監測該產生抗壞血酸磷酸鋅之過程。
較佳為,該氧化鋅懸浮液含有10至20毫克/毫升氧化鋅。該抗壞血酸磷酸鋅溶液宜包含介於50及70毫克/毫升間之抗壞血酸磷酸酯。
該氧化鋅與抗壞血酸磷酸酯之混合物的pH可使用任何與口腔保健配製物相容之酸或鹼來調整。較佳為,該pH係用酸調整。該酸宜為氫氯酸。一般認為改變該溶液之pH及/或使用試劑來調整該pH會改變所產生之抗壞血酸磷酸鋅的組成物。
可使用已知於此方面技藝中之任何適當方法,將附加之配體合併於該抗壞血酸磷酸鋅中。
抗壞血酸磷酸鋅複合物係藉著將氧化鋅之水懸浮液與抗壞血酸磷酸酯之水溶液混合,且將該產生之混合物的pH調整至約7.0而合成。該產生溶液之組成物係藉液體色層分離法及質譜測定法研究。形成具有三種抗壞血酸磷酸鋅複合物之混合物。該混合物以0.08mM之濃度可溶於水中。
材料與方法:製備氧化鋅(162毫克)於去離子水(10毫升)中之懸浮液。抗壞血酸磷酸酯(646毫克)於去離子水(10毫升)中之溶液。將等份量氧化鋅懸浮液(1毫升)與等份量抗壞血酸磷酸酯溶液(1毫升)混合。使用1N氫氯酸將產生之混合物的pH調整至約7.0。然後將該溶液於室溫靜置約3小時,直到獲得澄清溶液。該澄清溶液之樣品係使用液體色層分離電
噴灑電離-串聯質譜法(LC-ESI-MSMS)予以分析。
LC分析係使用配備ESI界面及安捷倫(Agilent)1100毛細管LC系統(型號安捷倫1100,安捷倫科技公司,Palo Alto,California,美國)之TSQ量子串聯質譜儀(Thermo-Electron Company,San José,California,美國)來進行。
該毛細管LC系統裝配有毛細管二元泵(型號G1376A)、二極管陣列偵測器(型號1315B)、微型真空脫氣機及恆溫管柱箱(thermostatted column compartment)(型號G1316A)。該毛細管泵係設定到微流模式。該LC分離係使用直徑2.1毫米及長度50毫米含5微米大小粒子之亞特蘭提斯(Atlantis)HILIC管柱(華特斯公司,Milford,Massachusetts,美國,組件編號186002012)進行。該流動相係由15%水及85%甲醇所組成。流速為每分鐘100微升且注入的體積為1微升。
該TSQ量子串聯質譜儀係於負離子模式中,於下列之條件下操作:於壓力35psi及5個單位時,氮氣(>99.99%純度)分別用作為屏蔽氣體及作為輔助氣體。該ESI噴霧電壓為4.5kV。該加熱之溫度係保持於350℃。該MS篩選範圍係由80至1200m/z。數據係使用Xcalibur軟體系統(Thermo-Electron Company,San José,California,美國)採集。
根據該質譜,一般認為產生三種鋅複合物。複合物1為抗壞血酸磷鋅(II)。複合物2為抗壞血酸磷氯鋅(II)。複合物3為抗壞血酸磷羥鋅(II)。
將實例1中所得到之複合物混合物之最小抑制濃度進行測定。發現抗壞血酸磷酸鋅複合物之混合物,比只有氧化鋅,只有抗壞血酸磷酸酯,及使用於口腔保健組成物中之習用抗微生物組成份鋅-賴胺酸複合物,具有更低之最小抑制濃度。
將實例1之抗壞血酸磷酸鋅、抗壞血酸磷酸酯、氧化鋅,及鋅-賴胺酸複合物,各自製備於水中之儲備溶液。各個溶液中之活性組成份的濃度為0.1M。將等份量之各試驗溶液(200微升)置於96孔洞盤之第一行。該儲備溶液之連續稀釋係於該盤上藉著將該儲備溶液與胰蛋白酶大豆肉汁以1:1基準混合而製備。該活性組成份之濃度係以由50mM至0.00488mM變化基準而製備。
製備具有光密度於610毫微米為0.2之黏放線菌(A.viscuosus)溶液。然後將等份量之黏放線菌溶液(100微升)加至各試驗之孔洞中。製備四個含TSB緩衝劑及黏放線菌溶液之控制孔洞。亦製備四個只含TSB緩衝劑之空白孔洞。
然後將該盤於37℃培育18小時。然後使用盤讀數器將各孔洞於610毫微米時之光密度予以記錄。
表1顯示所研究之化合物各自得到之光密度讀數。較低之光密度讀數係與較低之細菌濃度相關,且因而改良抗細菌效應。
該數據顯示,當以0.195mM或更大之數量存在時,抗壞血酸磷酸鋅抑制細菌之生長。於所有之濃度研究中,抗壞血酸磷酸鋅於抗細菌活性上比抗壞血酸磷酸酯或鋅-賴胺酸複合物產生更大的效果。以介於0.391mM及12.5mM間之濃度時,抗壞血酸磷酸鋅比氧化鋅產生更大的抑制效果。以0.195mM之劑量時,抗壞血酸磷酸鋅所產生之抑制效果與氧化鋅者大約相等。
氧化鋅於水狀態下為難溶。由於固體粒子之光散射,含固體粒子於液體中之懸浮液傾向具有高的表觀吸光度值。因此,於濃度25mM及以上之溶液中所觀察到異常高之光密度讀數係與固體沉澱物之存在一致。
抗壞血酸磷酸鋅顯示正性劑量反應,亦即,抗細菌效應隨濃度而提高。一般認為於氧化鋅時,一旦該氧化鋅之濃度超過溶解度極限,沒有觀察到抗細菌效應增加。因此,一般認為以高的濃度,抗壞血酸磷酸鋅比氧化鋅顯示更大的抑制細菌生長。
於口腔保健組成物中,特別於漱口劑配製物中,不想要存有不溶之組份。不溶組份可引起,例如,加工困難且當該組成物用於治療個體之方法中時,活性組成份之劑量於輸送中改變。因此,抗壞血酸磷酸鋅比氧化鋅具有更大的有用劑量範圍,由於其改良之溶解度。
含抗壞血酸磷酸鋅作為純化合物或混合物之本發明的範例潔牙劑係說明於表2中。
含抗壞血酸磷酸鋅作為純化合物或混合物之本發明的範例漱口劑配製物係說明於表3中。
如全文中所使用者,範圍係以簡略方式使用來說明該範圍內之各個及每一個數值。於該範圍內之任何數值可選擇作為該範圍之終點。此外,於本文中所引證之所有的參考,其等之全部內容係合併於本文中參考。萬一於本發明揭示內容中之定義與所引證之參考者發生衝突,則對照本發明之揭示內容。
除非另有指明,於本文中及於本說明書中任何地方所表達之所有的百分比及數量應瞭解係指重量百分比。所給定之數量係以該物質之活性重量計。
Claims (15)
- 一種含口腔可接受水性載劑及抗微生物組成份之口腔保健組成物,其中該抗微生物組成份包含至少一種抗壞血酸磷酸鋅。
- 如申請專利範圍第1項之組成物,其中至少一種抗壞血酸磷酸鋅係包含抗壞血酸磷鋅(II)(ascorbylphosphato zinc(II))。
- 如申請專利範圍第1項或申請專利範圍第2項之組成物,其中至少一種抗壞血酸磷酸鋅係包含抗壞血酸磷氯鋅(II)(ascorbylphosphatochlorido zinc(II))。
- 如申請專利範圍第1至3項中任一項之組成物,其中至少一種抗壞血酸磷酸鋅係包含抗壞血酸磷羥鋅(II)(ascorbylphosphatohydroxo zinc(II))。
- 如申請專利範圍第1項之組成物,其中至少一種抗壞血酸磷酸鋅係包含抗壞血酸磷鋅(II)、抗壞血酸磷氯鋅(II)及抗壞血酸磷羥鋅(II)之混合物。
- 如前述申請專利範圍中任一項之組成物,其中至少一種抗壞血酸磷酸鋅係以至少3.0mM之濃度於該組成物中。
- 如前述申請專利範圍中任一項之組成物,其中該組成物之pH係於6至8之範圍。
- 如前述申請專利範圍中任一項之組成物,其進一步包含至少一種組份選自於下列之群組,包括:表面活化劑、減敏感劑、美白劑、齒垢控制劑、磨蝕劑、黏合劑、增稠劑、去垢劑、黏附劑、泡沫調製劑、pH調節劑、口感劑、甜味劑、香味劑、著色劑、防腐劑、濕潤劑、氟化物離子來源及其組合物。
- 如前述申請專利範圍中任一項之組成物,其係為潔牙劑形式。
- 如申請專利範圍第1至8項中任一項之組成物,其係為漱口劑形式。
- 如前述申請專利範圍中任一項之組成物,係用於治療或預防人類或動物個體中之口腔疾病或障礙的方法,該方法包含施用該組成物至該個體之 口腔。
- 一種抗壞血酸磷酸鋅的用途,係用於口腔保健組成物作為抗微生物組成份。
- 一種如申請專利範圍第1至10項中任一項之組成物的用途,係用於製造用來治療或預防口腔之疾病或障礙的口腔保健產品。
- 一種口腔保健套組,其包含如申請專利範圍第1至11項中任一項之組成物。
- 一種製造口腔保健組成物之方法,其係包含下列之步驟:製備氧化鋅之懸浮液;製備抗壞血酸磷酸酯之溶液;混合該氧化鋅懸浮液及該抗壞血酸磷酸酯溶液;且該氧化鋅與抗壞血酸磷酸酯進行反應以便形成複合物。
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| PCT/US2012/070497 WO2014098817A1 (en) | 2012-12-19 | 2012-12-19 | Oral care composition |
Publications (2)
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| TW201438750A true TW201438750A (zh) | 2014-10-16 |
| TWI532503B TWI532503B (zh) | 2016-05-11 |
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| TW102144527A TWI532503B (zh) | 2012-12-19 | 2013-12-05 | 口腔保健組成物 |
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| EP (1) | EP2934440B1 (zh) |
| JP (1) | JP2016503790A (zh) |
| KR (1) | KR20150097495A (zh) |
| CN (1) | CN104853719B (zh) |
| AR (1) | AR094196A1 (zh) |
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| BR (1) | BR112015014447B1 (zh) |
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| TW (1) | TWI532503B (zh) |
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| US12151007B2 (en) | 2020-06-26 | 2024-11-26 | Colgate-Palmolive Company | Electrochemical tooth whitening composition and method thereof |
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| JPS63141921A (ja) * | 1986-12-04 | 1988-06-14 | Kao Corp | 口腔用組成物 |
| US5059416A (en) | 1989-06-26 | 1991-10-22 | Warner-Lambert Company | Zinc compound delivery system with improved taste and texture |
| JP3772468B2 (ja) * | 1997-06-11 | 2006-05-10 | 昭和電工株式会社 | L−アスコルビン酸−2−リン酸亜鉛塩及びその製造方法 |
| US6420419B1 (en) * | 1997-11-06 | 2002-07-16 | Showa Denko Kabushiki Kaisha | L-ascorbic acid 2-phosphate zinc salt and process for manufacturing the same |
| JP2000351905A (ja) * | 1999-04-05 | 2000-12-19 | Showa Denko Kk | アスコルビン酸誘導体含有組成物 |
| WO2002058662A2 (en) * | 2001-01-24 | 2002-08-01 | Oraceutical Llc | Topical oral care compositions |
| BR0209455A (pt) | 2001-05-10 | 2004-07-06 | Roche Vitamins Ag | Dentifrìcio |
| AU2003267393A1 (en) | 2002-11-04 | 2004-06-07 | Dsm Ip Assets B.V. | Oral care compositions comprising ascorbic acid derivative |
| CN1805692B (zh) * | 2003-06-16 | 2010-10-27 | 帝斯曼知识产权资产管理有限公司 | 宠物食品组合物 |
| EP1663126A1 (de) * | 2003-09-09 | 2006-06-07 | DSM IP Assets B.V. | Oral wirkendes im wesentlichen wasserfreies topisches mittel enthaltend ein oder mehrere oxidationsempfindliche stoffe |
| US20050271602A1 (en) | 2004-06-02 | 2005-12-08 | Nebojsa Milanovich | Method for inhibiting chemical staining of teeth |
| DK1791791T3 (da) * | 2004-09-27 | 2019-08-26 | Special Water Patents B V | Fremgangsmåder og sammensætninger til behandling af vand |
| US8337818B2 (en) | 2004-11-03 | 2012-12-25 | Colgate-Palmolive Company | Post-foaming dental mousse and methods utilizing the same |
| EP1698324A1 (en) * | 2004-11-09 | 2006-09-06 | The Procter & Gamble Company | Zinc-containing dentifrice compositions having an improved taste |
| US8858920B2 (en) | 2004-12-21 | 2014-10-14 | Colgate-Palmolive Company | Anti-caries oral care composition with xylitol |
| US8758838B2 (en) | 2005-08-31 | 2014-06-24 | Johnson & Johnson Consumer Companies, Inc. | Anti-inflammatory compositions and methods of use |
| EP1948236B1 (en) | 2005-09-27 | 2021-03-03 | Special Water Patents B.V. | Methods and compositions for treatment of skin |
| MY151134A (en) | 2005-12-21 | 2014-04-30 | Colgate Palmolive Co | Improved oral compositions comprising zinc citrate and / or tocopherol agents |
| US20110280855A1 (en) | 2006-10-23 | 2011-11-17 | Neil Levin | Vitamin c compositions |
| WO2010074025A1 (ja) * | 2008-12-24 | 2010-07-01 | ライオン株式会社 | 歯磨剤組成物 |
| MY163501A (en) | 2009-04-01 | 2017-09-15 | Colgate Palmolive Co | Anti-biofilm carbonate compouns for use in oral care compositions |
| TW201109022A (en) | 2009-06-03 | 2011-03-16 | Colgate Palmolive Co | Borinic compositions |
| AU2011227198A1 (en) | 2010-03-17 | 2012-10-04 | Arbonne International Llc | Topical skin care composition |
| MX2012011747A (es) | 2010-04-09 | 2012-11-16 | Unilever Nv | Composiciones para el cuidado oral. |
| BR112013010519A2 (pt) | 2010-10-27 | 2016-07-05 | Colgate Palmolive Co | composição de higiene oral compreendendo arginina e carbonato de cálcio |
| JP5716388B2 (ja) * | 2010-12-24 | 2015-05-13 | ライオン株式会社 | 歯磨剤組成物及び歯磨剤組成物におけるアスコルビン酸リン酸エステル又はその塩の安定化方法 |
| WO2012136574A2 (en) | 2011-04-04 | 2012-10-11 | Unilever Plc | Oral care compositions |
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2012
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- 2012-12-19 KR KR1020157015478A patent/KR20150097495A/ko not_active Withdrawn
- 2012-12-19 EP EP12809988.4A patent/EP2934440B1/en active Active
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- 2012-12-19 US US14/652,780 patent/US9757320B2/en active Active
- 2012-12-19 RU RU2015129108A patent/RU2636218C2/ru active
- 2012-12-19 JP JP2015549325A patent/JP2016503790A/ja active Pending
- 2012-12-19 CN CN201280077846.4A patent/CN104853719B/zh active Active
- 2012-12-19 MX MX2015007677A patent/MX352313B/es active IP Right Grant
- 2012-12-19 WO PCT/US2012/070497 patent/WO2014098817A1/en not_active Ceased
- 2012-12-19 AU AU2012397258A patent/AU2012397258B2/en active Active
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2015
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- 2015-06-15 IL IL239422A patent/IL239422A0/en unknown
Also Published As
| Publication number | Publication date |
|---|---|
| US9757320B2 (en) | 2017-09-12 |
| PH12015501237A1 (en) | 2015-08-17 |
| KR20150097495A (ko) | 2015-08-26 |
| RU2015129108A (ru) | 2017-01-25 |
| CN104853719A (zh) | 2015-08-19 |
| WO2014098817A1 (en) | 2014-06-26 |
| EP2934440B1 (en) | 2018-02-21 |
| MX2015007677A (es) | 2015-09-07 |
| CN104853719B (zh) | 2017-11-03 |
| TWI532503B (zh) | 2016-05-11 |
| US20160008254A1 (en) | 2016-01-14 |
| EP2934440A1 (en) | 2015-10-28 |
| CA2892408C (en) | 2019-10-08 |
| IL239422A0 (en) | 2015-07-30 |
| AR094196A1 (es) | 2015-07-15 |
| BR112015014447B1 (pt) | 2019-07-09 |
| MX352313B (es) | 2017-11-17 |
| AU2012397258A1 (en) | 2015-06-11 |
| RU2636218C2 (ru) | 2017-11-21 |
| JP2016503790A (ja) | 2016-02-08 |
| CA2892408A1 (en) | 2014-06-26 |
| AU2012397258B2 (en) | 2015-10-01 |
| BR112015014447A2 (pt) | 2017-07-11 |
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