TW201605482A - 含鋅、錫及氟化物離子源之口腔組成物 - Google Patents
含鋅、錫及氟化物離子源之口腔組成物 Download PDFInfo
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- TW201605482A TW201605482A TW104117590A TW104117590A TW201605482A TW 201605482 A TW201605482 A TW 201605482A TW 104117590 A TW104117590 A TW 104117590A TW 104117590 A TW104117590 A TW 104117590A TW 201605482 A TW201605482 A TW 201605482A
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- Prior art keywords
- weight
- composition
- pyrophosphate
- citric acid
- zinc
- Prior art date
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- 239000000203 mixture Substances 0.000 title claims abstract description 252
- KRHYYFGTRYWZRS-UHFFFAOYSA-M Fluoride anion Chemical compound [F-] KRHYYFGTRYWZRS-UHFFFAOYSA-M 0.000 title claims description 16
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 title description 20
- 229910052725 zinc Inorganic materials 0.000 title description 20
- 239000011701 zinc Substances 0.000 title description 20
- IUTCEZPPWBHGIX-UHFFFAOYSA-N tin(2+) Chemical compound [Sn+2] IUTCEZPPWBHGIX-UHFFFAOYSA-N 0.000 title description 8
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 claims abstract description 84
- -1 fluoride ions Chemical class 0.000 claims abstract description 40
- PTFCDOFLOPIGGS-UHFFFAOYSA-N Zinc dication Chemical compound [Zn+2] PTFCDOFLOPIGGS-UHFFFAOYSA-N 0.000 claims abstract description 38
- XLOMVQKBTHCTTD-UHFFFAOYSA-N Zinc monoxide Chemical compound [Zn]=O XLOMVQKBTHCTTD-UHFFFAOYSA-N 0.000 claims abstract description 20
- 150000002500 ions Chemical class 0.000 claims abstract description 10
- 239000011787 zinc oxide Substances 0.000 claims abstract description 10
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 33
- 239000000551 dentifrice Substances 0.000 claims description 31
- 239000002562 thickening agent Substances 0.000 claims description 24
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 claims description 23
- FQENQNTWSFEDLI-UHFFFAOYSA-J sodium diphosphate Chemical compound [Na+].[Na+].[Na+].[Na+].[O-]P([O-])(=O)OP([O-])([O-])=O FQENQNTWSFEDLI-UHFFFAOYSA-J 0.000 claims description 18
- 229910000420 cerium oxide Inorganic materials 0.000 claims description 14
- BMMGVYCKOGBVEV-UHFFFAOYSA-N oxo(oxoceriooxy)cerium Chemical compound [Ce]=O.O=[Ce]=O BMMGVYCKOGBVEV-UHFFFAOYSA-N 0.000 claims description 14
- 235000011180 diphosphates Nutrition 0.000 claims description 13
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 claims description 12
- 239000003082 abrasive agent Substances 0.000 claims description 12
- ANOBYBYXJXCGBS-UHFFFAOYSA-L stannous fluoride Chemical compound F[Sn]F ANOBYBYXJXCGBS-UHFFFAOYSA-L 0.000 claims description 12
- 229960002799 stannous fluoride Drugs 0.000 claims description 12
- 235000019818 tetrasodium diphosphate Nutrition 0.000 claims description 12
- 239000003906 humectant Substances 0.000 claims description 11
- 239000004094 surface-active agent Substances 0.000 claims description 11
- ATJFFYVFTNAWJD-UHFFFAOYSA-N Tin Chemical compound [Sn] ATJFFYVFTNAWJD-UHFFFAOYSA-N 0.000 claims description 10
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- KWIUHFFTVRNATP-UHFFFAOYSA-N glycine betaine Chemical compound C[N+](C)(C)CC([O-])=O KWIUHFFTVRNATP-UHFFFAOYSA-N 0.000 claims description 9
- 229940048084 pyrophosphate Drugs 0.000 claims description 9
- 239000001509 sodium citrate Substances 0.000 claims description 9
- 229910001432 tin ion Inorganic materials 0.000 claims description 9
- 239000007853 buffer solution Substances 0.000 claims description 8
- 239000001768 carboxy methyl cellulose Substances 0.000 claims description 7
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- 230000036541 health Effects 0.000 claims description 7
- 229920001223 polyethylene glycol Polymers 0.000 claims description 7
- HRXKRNGNAMMEHJ-UHFFFAOYSA-K trisodium citrate Chemical compound [Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O HRXKRNGNAMMEHJ-UHFFFAOYSA-K 0.000 claims description 7
- 229940038773 trisodium citrate Drugs 0.000 claims description 7
- 239000002202 Polyethylene glycol Substances 0.000 claims description 6
- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 claims description 6
- 229960003237 betaine Drugs 0.000 claims description 6
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- 229920002678 cellulose Polymers 0.000 claims description 5
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- XPPKVPWEQAFLFU-UHFFFAOYSA-J diphosphate(4-) Chemical compound [O-]P([O-])(=O)OP([O-])([O-])=O XPPKVPWEQAFLFU-UHFFFAOYSA-J 0.000 claims description 5
- 238000000034 method Methods 0.000 claims description 5
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- 230000000844 anti-bacterial effect Effects 0.000 claims description 4
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- 229940048086 sodium pyrophosphate Drugs 0.000 claims description 4
- 239000001577 tetrasodium phosphonato phosphate Substances 0.000 claims description 4
- 206010061218 Inflammation Diseases 0.000 claims description 3
- ODKSFYDXXFIFQN-BYPYZUCNSA-N L-arginine Chemical compound OC(=O)[C@@H](N)CCCN=C(N)N ODKSFYDXXFIFQN-BYPYZUCNSA-N 0.000 claims description 3
- 235000014852 L-arginine Nutrition 0.000 claims description 3
- 229930064664 L-arginine Natural products 0.000 claims description 3
- 208000025157 Oral disease Diseases 0.000 claims description 3
- 239000007844 bleaching agent Substances 0.000 claims description 3
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- 230000004054 inflammatory process Effects 0.000 claims description 3
- 208000030194 mouth disease Diseases 0.000 claims description 3
- 229940088594 vitamin Drugs 0.000 claims description 3
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- 239000011782 vitamin Substances 0.000 claims description 3
- 150000003751 zinc Chemical class 0.000 claims description 3
- 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 3
- 229910000165 zinc phosphate Inorganic materials 0.000 claims description 3
- 108090000790 Enzymes Proteins 0.000 claims description 2
- 102000004190 Enzymes Human genes 0.000 claims description 2
- 230000032770 biofilm formation Effects 0.000 claims description 2
- 239000004088 foaming agent Substances 0.000 claims description 2
- 150000007524 organic acids Chemical class 0.000 claims description 2
- 125000004437 phosphorous atom Chemical group 0.000 claims description 2
- 230000007505 plaque formation Effects 0.000 claims description 2
- YUOWTJMRMWQJDA-UHFFFAOYSA-J tin(iv) fluoride Chemical compound [F-].[F-].[F-].[F-].[Sn+4] YUOWTJMRMWQJDA-UHFFFAOYSA-J 0.000 claims 3
- 239000003755 preservative agent Substances 0.000 claims 1
- 230000002335 preservative effect Effects 0.000 claims 1
- 239000003795 chemical substances by application Substances 0.000 description 18
- 239000000463 material Substances 0.000 description 18
- 235000015165 citric acid Nutrition 0.000 description 17
- 150000002978 peroxides Chemical class 0.000 description 13
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- 239000003945 anionic surfactant Substances 0.000 description 7
- XPPKVPWEQAFLFU-UHFFFAOYSA-N diphosphoric acid Chemical compound OP(O)(=O)OP(O)(O)=O XPPKVPWEQAFLFU-UHFFFAOYSA-N 0.000 description 7
- 239000000047 product Substances 0.000 description 7
- GWEVSGVZZGPLCZ-UHFFFAOYSA-N Titan oxide Chemical compound O=[Ti]=O GWEVSGVZZGPLCZ-UHFFFAOYSA-N 0.000 description 6
- XEFQLINVKFYRCS-UHFFFAOYSA-N Triclosan Chemical compound OC1=CC(Cl)=CC=C1OC1=CC=C(Cl)C=C1Cl XEFQLINVKFYRCS-UHFFFAOYSA-N 0.000 description 6
- 230000002272 anti-calculus Effects 0.000 description 6
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- 229910021645 metal ion Inorganic materials 0.000 description 6
- 230000002087 whitening effect Effects 0.000 description 6
- 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 6
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Abstract
一種口腔保健組成物,其包含錫離子源、氟離子源及不可溶鋅離子源,例如氧化鋅。組成物含足量檸檬酸以提升可溶鋅離子量。
Description
一種口腔保健組成物,其包含錫離子源、氟離子源及不可溶鋅離子源,例如氧化鋅。組成物含足量檸檬酸以提升可溶鋅離子量。
口腔保健產品中的試劑必須提供抗菌、抗蛀牙、抗琺瑯質侵蝕、口氣清新等改善的益處。先前技術中描述鋅離子、錫離子及/或氟離子在口腔中的抗菌成效,且已有眾多嘗試試圖製造整合鋅離子、錫離子及/或氟離子的潔齒劑組成物以發揮減少牙菌斑、牙齦發炎、齒齦炎等療效的好處。特別是,檸檬酸鋅等可溶鋅離子已用於潔齒劑組成物中。
美國專利申請出版2012/0207686(686出版)等亦已公開氧化鋅等不可溶鋅離子源用於潔齒劑。然而,不可溶鋅離子之使用通常因可運送到牙齒表面的鋅離子量過低而受限,且當所使用鋅離子量過高,則會使消費者感到不必要的澀味。
較佳為提供一種口腔保健組成物,其在預防及/或減少生物薄膜、牙菌斑、口腔發炎等方面展現較先前已知的組成物更
優異的效能。
本發明係關於一種口腔保健組成物,例如潔齒劑組成物,可在有效運送離子至口腔的低水(較佳為單相)系統中有效結合錫離子源、氟離子源及不可溶鋅離子源。已知錫及鋅離子有助於減少/預防齒齦炎及牙周炎等口腔發炎、牙菌斑形成、口腔生物薄膜形成、牙齒敏感度並增進口氣清新。
本發明係關於一種口腔保健組成物,包含:(a)口腔可接受載體;(b)氟離子源;(c)錫離子源;(d)不可溶鋅離子源;(e)緩衝系統,包含檸檬酸,其中檸檬酸含量至少為組成物的1重量%;及其中組成物具有低於15重量%的總水含量。
在另一態樣中,在此描述的實施方式提供一種治療及預防牙菌斑累積的方法,包含將上述潔齒劑成分運送到口腔。
應理解即使詳細說明及特定實例指出本發明的較佳實施方式,但其意圖僅為例示且未意圖限制本發明的範圍。
如全文中所使用的範圍係用作描述該範圍內每一個值的簡略表達方式。範圍內的任何值皆可選作範圍的邊界。此外,上述所列的參考文獻全文皆通過引用結合到本說明書中。然而,若本案揭示內容之定義與引用的參考文獻之定義有所衝突,以本案揭示內容為準。
除非另外說明,本規格所述的所有百分比和數量皆為重量%。所列出的數量係以材料的有效重量為基準。
在此說明中,除非另外提及,單數之使用亦包括複數。例如,「一錫離子源」亦涵蓋使用多於一個鋅離子源。
在此所使用「較佳的」及「較佳為」係指在某些情況下提供某些好處的本發明之實施方式。然而,在相同或其他情況下亦可使用其他實施方式。此外,詳述一或多項實施方式並不意味其他實施方式無法使用,且未意圖將其他實施方式從本發明範圍排除。
不可溶鋅離子源
在一實施方式中,不可溶鋅離子源係為不可溶鋅離子鹽。在此所使用的「不可溶」一詞係指在25℃水溶液pH7中溶解度低於0.1重量%(以組成物的重量為基準)的材料或化合物。亦應理解在較低或較高pH,不可溶鋅離子源可變成顯著較可溶。適合的不可溶鋅離子源的實例包括氧化鋅、磷酸鋅、焦磷酸鋅和其他鋅組成物。不可溶鋅離子源較佳為氧化鋅。
一般而言,可傳送給口腔表面的可溶鋅離子濃度愈高,成效愈高。本發明在來自不可溶鋅離子源的組成物中提供較高濃度
的鋅離子。本發明的組成物通常具有高於50%可溶鋅離子(例如,對於含1重量%(1.0)不可溶鋅離子源的組成物,經過13週以40℃熟成後,鋅含量將高於0.5%(0.5)),在其他實施方式中,經過13週以40℃熟成後,高於60%,高於70%,或高於80%。
鋅離子源含量通常從0.1重量%至2重量%,以最終組成物重量為基準。在一實施方式中,鋅離子源含量介於0.5重量%至1.5%,或介於0.9%至1.1%。
亞錫離子源
本發明的組成物包含亞錫離子源。亞錫離子源可為含無機或有機反離子的可溶或不可溶亞錫組成物。實例包含亞錫的氟化物、氯化物、氟氯化物、乙酸鹽、六氟鋯酸物、硫化物、酒石酸鹽、葡萄糖酸鹽、檸檬酸鹽、蘋果酸鹽、甘胺酸鹽、焦磷酸鹽、偏磷酸鹽、草酸鹽、磷酸鹽、碳酸鹽和氧化物。
包含亞錫鹽的口腔組成物,特別是氟化亞錫和氯化亞錫,係敘述於美國專利號5,004,597。關於亞錫鹽潔齒劑的其他敘述係出現於美國專利號5,578,293。較佳的亞錫鹽為氟化亞錫和二水合氯化亞錫。亞錫鹽的其他實例包含乙酸亞錫、酒石酸亞錫和檸檬酸亞錫酸鈉。
一般而言,可傳送至口腔表面的可溶亞錫離子濃度愈高,則成效愈高。本發明在來自不可溶鋅離子源的組成物中提供較高濃度的亞錫離子。本發明的組成物通常具有高於50%的可溶亞錫離子,在其他實施方式中,經過13週以40℃熟成後,高於60%,高於70%,高於80%,或高於90%。
亞錫離子源含量通常從0.05重量%至5重量%,以最
終組成物重量為基準。在一實施方式中,亞錫離子源含量從0.1重量%至1%,或從0.35%至0.55%。
有效含量的亞錫和鋅離子衍生自存在於口腔護理組成物中的離子源。有效含量定義為至少1000ppm金屬(鋅加上亞錫)離子,較佳為2,000ppm至15,000ppm。更佳為,金屬離子含量介於3,000ppm至13,000ppm,甚至更佳為介於4,000ppm至10,000ppm。此為要傳送至牙齒表面之組成物中的金屬離子總含量(亞錫和鋅)。
綜合金屬離子源(亞錫和鋅)含量通常從0.15%至7%,以最終組成物重量為基準。較佳為,金屬離子源含量從0.6至2.5%,更佳為從1.25%至1.65%。
氟離子源
氟離子源在此為可提供游離氟離子的氟化物源。可溶氟離子源包含氟化鈉、氟化亞錫、氟化銦、氟化鋅和單氟磷酸鈉。氟化鈉和氟化亞錫係為較佳可溶氟離子源。美國專利號2,946,725和美國專利號3,678,154中公開此種氟離子源等。
本組成物中的氟離子源較佳為在消費者使用組成物刷洗之前的儲存期間以組成物中的固態分散形式存在。本組成物中的水含量過低,使氟化物源於儲存期間無法溶解於組成物中。因此,氟離子和聚磷酸鹽等其他成分(或矽酸,若有的話)之間的交互作用會在儲存期間大幅減少,而在儲存期間提供穩定的組成物。當組成物在刷洗期間與唾液及/或水接觸時,氟化物源較佳為將被分散且活性離子將被傳送到口腔。
本組成物可包含可提供從50ppm至3500ppm、較佳為
從500ppm至3000ppm游離氟離子的可溶氟離子。若要提供理想的氟離子含量,氟離子源含量在口腔保健組成物總含量中可從0.1%至5%,在一實施方式中,從0.2%至1%,甚至從0.3至0.6%,以組成物總重量為基準。
緩衝系統
在此描述的組成物亦包含由檸檬酸構成的緩衝系統。令人驚訝地,已知經過8或13週以40℃熟成後,高於0.6%(以口腔保健組成物重量為基準)的檸檬酸將導致組成物中出現明顯更多鋅離子及/或亞錫離子,其來自組成物中個別鋅及/或亞錫離子源。在部分實施方式中,檸檬酸含量為0.5-4重量%或1-3重量%,或1.1-1.5重量%或1.8-2.2重量%或1.3%或2%,以口腔保健組成物的重量為基準。在一實施方式中,緩衝系統包含檸檬酸和檸檬酸鈉,特別是檸檬酸三鈉。在此使用的緩衝劑係指可用於將組成物pH調整成pH 3.0至pH 10、更典型為6至8的試劑。
除了檸檬酸,可選擇性存在的其他緩衝劑包含鹼金屬氫氧化物、氫氧化鋁、有機鋁化合物、碳酸鹽、倍半碳酸鹽、硼酸鹽、矽酸鹽、磷酸鹽、咪唑及其混合物。特定緩衝劑包含磷酸單鈉、磷酸三鈉、苯甲酸鈉、苯甲酸、氫氧化鈉、氫氧化鉀、鹼金屬碳酸鹽、碳酸鈉、咪唑及焦磷酸鹽。緩衝劑總含量通常從0.1%至30%,或從0.1%至10%,或從0.3%至3%,以現有組成物重量為基準。
水總含量
用於製造適合市售的口腔組成物之水較佳應為具有低離子含量且不含有機不純物。在潔齒劑組成物中,水通常低於20重量%,或低於15重量%,或從低於15%至高於10重量%,以此處
的組成物重量為基準。水含量包含所加入的游離水及由其他材料(例如矽酸、界面活性劑溶液及/或有色溶液)帶來的游離水。
口腔可接受載體
在某些實施方式中,本發明提供包含口腔可接受載體或媒介物的組成物。在此使用的「口腔可接受載體」一詞和「口腔可接受媒介物」一詞可交換使用,係指可安全用於本組成物且具有合理益處/風險比例的材料或材料組合,其他成分可與上述材料相關,同時保有明顯的臨床成效。選擇此種載體材料時,應與組成物的其他成分相容,且較佳為不大幅減低其他成分的成效。選取特定載體成分時,必須考慮所需產品形式,包括潔齒劑、潤濕劑、凝膠和塗料。
可用於載體中的材料包含但不限於:黏著劑、增稠劑、黏度改質劑、稀釋劑、界面活性劑、抗牙結石劑、研磨劑、泡沫調節劑、美白劑(例如過氧化物、過氧化物活化劑、過氧化物穩定劑)、pH改質劑、保濕劑、口感劑、甜味劑、調味劑、著色劑及其組合。
黏著劑
在此所使用的「黏著劑」一詞係指可提升成分對其所施加的口腔表面之黏著性的材料或材料組合。此種黏著劑包含但不限於:黏著劑、薄膜形成材料及黏度增進劑;例如,親水性有機聚合物、疏水性有機聚合物、聚矽氧膠、聚矽氧黏著劑、二氧化矽及其組合。在一實施方式中,黏著劑係為平均分子量為30,000至1,000,000、例如300,000至800,000的甲基乙烯基醚/馬來酸酐共聚物。美國專利號5,047,490和4,627,977特別說明聚甲基乙烯基醚/馬來酸酐共聚物的製造。聚甲基乙烯基醚/馬來酸酐共聚物亦有商標
名稱為Gantrez® AN(來自ISP(Ashland),Wayne,N.J.)的市售產品。
增稠劑
本發明的潔齒劑組成物可被加入作為黏合系統的一或多個增稠劑。增稠劑總含量通常從0%至3重量%,或從0.1%至1.5重量%,或從0.2%-0.5重量%,以口腔保健組成物的重量為基準。
一種上述增稠劑為聚乙烯吡咯烷酮(PVP),特別是交聯的PVP,可選擇性搭配三仙膠等膠。其他增稠劑包含多醣類、卡波姆(carbomer)、泊洛沙姆(poloxamer)、經改質纖維素,例如羧甲基纖維素及其混合物。在部分實施方式中,此等增稠劑提供會帶給低水口腔保健組成物理想的一致性和凝膠性。先前已知凝膠材料在有水的情況下會提供理想的流變性,而當缺乏用於活化凝膠黏著特性的水時,保濕劑通常會提供較不佳的流變性。特別是甘油保濕劑更是如此。增稠劑亦可包含無機增稠劑。
在此適用作為增稠劑的膠等多醣類包含卡拉膠(carageenan)、結冷膠(gellan gum)、刺槐豆膠(locust bean gum)、三仙膠及其混合物。卡拉膠是衍生自海藻的多醣類,已知可用作牙膏的黏著劑或增稠劑,請參閱美國專利號6,187,293 B1和6,162,418。卡拉膠有數種類型,可依照海藻源及/或其硫化量和位置來辨別。適合用於本發明者為κ卡拉膠、經改質κ卡拉膠、卡拉膠、經改質卡拉膠及其混合物。在此適合使用的卡拉膠包含FMC公司市售的「Viscarin」系列,包括但不限於Viscarin TP 329、Viscarin TP 388及Viscarin TP 389。
結冷膠是另一種適合用於此處的多醣類,係為假單胞
菌(pseudomonas elodea)有氧發酵的多醣類,當其含量為0.1%至3%,較佳為從0.4%至1.8%時,亦可形成可接受的低水陣列。
刺槐豆膠和三仙膠亦為適合用於此處的多醣類。當組成物中的水含量低於10%,作為增稠劑的刺槐豆膠或三仙膠可形成穩定且可接受的潔齒劑陣列。
泊洛沙姆在此於低水陣列中亦適合作增稠劑。泊洛沙姆為氧化乙烯和氧化丙烯的合成嵌段共聚物,有數種類型。在此較佳為泊洛沙姆407,可部分溶於水中。當溫度高於65℃,可溶於甘油。例如可從美國紐澤西BASF CORPORATION取得POLOXAMER 407®。
卡波姆在低水陣列中亦適合作增稠劑,特別是無水陣列。
羥乙基纖維素和CMC等經改質纖維素在低水陣列中亦為良好的增稠劑。由於水含量在本組成物中受限,因此較佳為使用含疏水鏈(C12-C20)經改質羥乙基纖維素以增加此增稠劑在其他低極性溶劑(例如甘油、丙二醇和聚乙二醇)的溶解度和水合性。
增稠劑可包含無機增稠劑,例如膠態矽酸鋁鎂或微粒二氧化矽以改善結構。可使用其他增稠劑(若有的話),含量從0.1%至15%,較佳為從0.1%至5%,以口腔保健組成物的重量為基準。
保濕劑
保濕劑用於避免牙膏組成物接觸空氣而硬化,且某些保濕劑亦可帶給牙膏組成物理想的甜味。適用於本發明的保濕劑包括甘油、山梨糖醇、聚乙二醇、聚丙二醇及其混合物,特別是其混合物。保濕劑含量通常從0.1%至70%,較佳為從1%至60%,更佳
為從15%至55%,以組成物的重量為基準。
據信保濕劑對於低水陣列的黏度有明顯的影響。例如,使用多醣類作為組成物中的增稠劑時,當甘油或聚乙二醇增加時,陣列的黏度會增加。反之,當組成物中的聚丙二醇增加時,陣列黏度會下降。
抗牙結石劑
在本發明的多個實施方式中,口腔保健組成物可包含抗牙結石(齒垢控制)劑。一般而言,齒垢控制劑被歸類為不相容於部分美白劑的藥劑,但本發明的實施方式在單相美白組成物中包含齒垢控制劑和美白劑。適合的抗牙結石劑包括但不限於磷酸鹽和聚磷酸鹽(例如焦磷酸鹽和三聚磷酸鹽),聚氨基丙磺酸(polyaminopropanesulfonic acid)(AMPS)、六偏磷酸鹽、三水合檸檬酸鋅、聚胜肽(例如聚天冬氨酸和聚麩胺酸)、聚烯烴磺酸鹽、聚烯烴磷酸鹽和二磷酸鹽(例如EHDP;AHP)。口腔保健組成物可包含不同抗牙結石劑的混合物。在一較佳實施方式中,使用焦磷酸四鈉(TSPP)、三聚磷酸鈉(STPP)、焦磷酸四鉀(TKPP)或其混合物。抗牙結石劑可包含0.1%至30%、0.1%至15%、1%至10%或2%至6%(重量百分比)。
研磨劑
研磨材料亦可包含在牙膏組成物中。用於本發明組成物的研磨材料可為不過度磨損象牙質的任何材料。典型的研磨材料包括含有凝膠和沈澱物的二氧化矽;氧化鋁;磷酸鹽,包括正磷酸鹽、聚偏磷酸鹽和焦磷酸鹽;及其混合物。特定實例包括二水合正磷酸二鈣、焦磷酸鈣、磷酸三鈣、聚偏磷酸鈣、不可溶聚偏磷酸鈣、
水合氧化鋁、β焦磷酸鈣;碳酸鈣及含樹脂研磨材料,例如尿素和甲醛的粒狀濃縮產物,以及美國專利號3,070,510中所揭露的其他材料。亦可使用研磨劑的混合物。若潔齒劑組成物或特定相包含平均鏈長為4或以上的聚磷酸鹽,則含鈣研磨劑和氧化鋁並非較佳的研磨劑。最佳研磨劑為二氧化矽。
較佳為使用多種類型的二氧化矽牙齒研磨劑,原因是其具有格外優異的牙齒清潔及研磨成效,同時不會損害牙齒琺瑯質或象牙質。在此,二氧化矽研磨材料及其他研磨材料通常具有0.1至30微米、較佳為5至15微米的平均粒子大小。研磨劑可為沈澱的二氧化矽或二氧化矽凝膠,例如美國專利號3,538,230和美國專利號3,862,307中描述的二氧化矽乾凝膠。較佳為使用來自W.R.Grace & Company,Davison Chemical Division且商標名為「SYLOID®」的二氧化矽乾凝膠。較佳為亦可使用沈澱的二氧化矽材料,例如來自J.M.Huber Corporation且商標名為「ZEODENT®」、特別是「Zeodent 119」的二氧化矽。適用於本發明牙膏的二氧化矽牙齒研磨劑類型詳情係描述於美國專利號4,340,583。可用的二氧化矽研磨劑亦描述於美國專利號5,589,160;5,603,920;5,651,958;5,658,553及5,716,601。在此描述的口腔保健組成物中之研磨劑含量通常為組成物重量的6%至70%。較佳為牙膏包含佔組成物重量10%至50%的研磨劑。
過氧化物源
本發明可在組成物中包含過氧化物源。過氧化物源係選自含過氧化氫、過氧化鈣、過氧化尿素及其混合物。較佳的過氧化物源為過氧化鈣。以下含量代表過氧化物原料的含量,不過過氧化物源可包含過氧化物以外的成分。本組成物可包含從0.01%至
10%、較佳為從0.1%至5%、更佳為從0.2%至3%、最佳為從0.3%至0.8%過氧化物源,以潔齒劑組成物的重量為基準。
鹼金屬重碳酸鹽
組成物亦可包含鹼金屬重碳酸鹽。鹼金屬重碳酸鹽可溶於水,且除非已經過安定化,否則在水溶液系統中會有釋放二氧化碳的傾向。重碳酸鈉,亦稱為烘焙粉,為較佳的鹼金屬重碳酸鹽。鹼金屬重碳酸鹽亦可發揮緩衝劑的作用。本組成物可包含從0.5%至50%、較佳為從0.5%至30%、更佳為從2%至20%、最佳為從5%至18%的鹼金屬重碳酸鹽,以潔齒劑組成物重量為基準。
界面活性劑
組成物亦可包含界面活性劑,通常亦可稱為泡沫劑。適合的界面活性劑在廣泛的pH範圍皆具有某種量的穩定性和泡沫。界面活性劑可為陰離子系、非離子系、兩性系、兩性離子系、陽離子系及其混合物。在此可使用的陰離子系界面活性劑包含烷基硫酸的水溶性鹽類,在烷基自由基中具有8至20個碳原子(例如烷基硫酸鈉),以及脂肪酸之磺酸化單甘油酯的水溶性鹽類,具有8至20個碳原子。月桂基硫酸鈉和椰子單甘油磺酸鈉為此類型陰離子系界面活性劑的實例。其他適合的陰離子系界面活性劑為肌胺酸鹽,例如月桂基肌胺酸鈉及十二烷基苯磺酸鈉。亦可使用陰離子系界面活性劑的混合物。美國專利號3,959,458中公開許多適合的陰離子系界面活性劑。
組成物中可使用的非離子系界面活性劑可廣泛定義為將伸烷基氧基群(親水性)及有機疏水化合物(可為脂肪族或烷基芳香族)濃縮而製造的化合物。適合的非離子性界面活性劑包括泊洛沙
姆(poloxamer)(商標名:PLURONIC®)、聚氧乙烯、聚氧乙烯山梨糖酯(商標名:TWEENS®)、Polyoxyl 40氫化蓖麻油、脂肪醇乙氧化物、烷基酚的聚乙二醇濃縮物、衍生自將環氧乙烷連同環氧丙烷及乙二胺的反應產物濃縮而得到的產物、脂肪族醇的環氧乙烷濃縮物、長鏈二烴基亞碸及此種材料的混合物。可用於本發明的兩性系界面活性劑可廣泛定義為脂肪族二級或三級胺的衍生物,其中脂肪族自由基可為直鏈或支鏈,且其中任一脂肪族取代基包含8至18個碳原子,而另一包含陰離子系水溶性基群,例如羧酸鹽、磺酸鹽、硫酸鹽、磷酸鹽或膦酸鹽。其他適用的兩性系界面活性劑為甜菜鹼,特別是烷基醯胺甜菜鹼。亦可使用兩性系界面活性劑的混合物。美國專利號4,051,234中公開許多此等適合的非離子系和兩性系界面活性劑。本組成物通常包含一種或多種界面活性劑,每種的含量從0.25%至12%,較佳為從0.5%至8%,最佳為從1%至6%,以組成物的重量為基準。
在一實施方式中,口腔保健組成物包括含月桂基硫酸鈉、烷基醯胺甜菜鹼或其混合物的界面活性劑系統。
抗菌劑
本發明組成物亦可包含抗菌劑。此種抗菌劑中包括非水溶性非陽離子抗菌劑,例如鹵化二苯基醚,酚化合物,包括酚及其同系物,單烷基及聚烷基和芳香族鹵酚,間苯二酚及其衍生物,雙酚化合物及鹵化水楊醯苯胺(salicylanilide),苯甲酸酯及鹵化羰[基]胺苯(carbanilide),聚酚及草藥。水溶性抗菌劑包含四級銨鹽和二雙胍鹽等。三氯沙(triclosan)單磷酸鹽係為較佳的其他水溶性抗菌劑。四級銨中,四級氮的一個或兩個取代基具有從8至20、通常從10
至18的碳原子的碳鏈長度,而其他取代基(通常為烷基或苯甲基)具有較低數量碳原子,例如從1至7個碳原子,通常為甲基或乙基。十二基三甲基溴化銨、十四基氯化吡啶、溴化多米芬(domiphen bromide)、N-十四基-4-乙基氯化吡啶、十二基二甲基(2-苯氧基)溴化銨、芐基二甲基硬脂醯氯化銨、十六基氯化吡啶、季銨化5-胺-1,3-雙(2-乙基-己基)-5-甲基六氢嘧啶、苯扎氯銨(benzalkonium chloride)、苄索氯銨(benzethonium chloride)和甲基苄索氯銨為典型四級銨抗菌劑的實例。其他化合物為公開在1980年6月3日授予專利給Bailey的美國專利號4,206,215中的雙[4-(R-胺基)-1-吡啶]烷烴。
在此亦包含其他抗菌劑,例如雙甘胺酸銅、甘胺酸銅、檸檬酸鋅、乳酸鋅。亦可使用酶,包括糖苷內切酶、木瓜蛋白酶、葡聚糖酶、齒斑葡聚糖酶及其混合物。此種試劑公開於美國專利號2,946,725和美國專利號4,051,234。特定抗菌劑包括氯己定(chlorhexidine)、三氯沙(triclosan)、三氯生單磷酸鹽(triclosan monophosphate)和調味油例如百里酚(thymol)。三氯沙為包含在本發明組成物中的較佳抗菌劑。三氯沙和此種類型的其他試劑係公開於美國專利號5,015,466和美國專利號4,894,220。此種試劑含量可從0.01%至1.5%,以組成物的重量為基準。
亦可在本發明組成物中加入二氧化鈦。二氧化鈦係為组成物增加不透明性的白色粉末。二氧化鈦含量通常從0.25%至5%,以組成物的重量為基準。
亦可在本發明組成物中加入著色劑。著色劑可為水溶液形式,較佳為水溶液中有1%著色劑。有色溶液含量通常從0.01%至約5%,以組成物的重量為基準。
亦可在組成物中加入調味體系。適合的調味組成物包括冬青油、薄荷油、留蘭香油、丁香花蕾油、薄荷醇、茴香腦、水楊酸甲酯、桉葉油素、肉桂、1-薄荷基乙酸酯、鼠尾草、丁香油酚、歐芹油、噁烷酮(oxanone)、α-紫羅蘭酮、馬鬱蘭、檸檬檬、柳橙、丙烯基鄰乙氧苯酚、肉桂、香草醛、乙基香草醛、天芥菜精、4-順式-庚烯縮醇、雙乙醯、甲基-對叔丁基苯基乙酸酯及其混合物。冷卻劑亦可為調味體系的一部分。在本發明組成物中較佳的冷卻劑為對薄荷烷羧醯胺試劑,例如N-乙基-對薄荷烷-3-羧醯胺(在商業上稱為「WS-3」)及其混合物。以所述組合物的重量計,調味體系在組成物中的使用含量通常從0.001%至5%,以組成物的重量為基準。
亦可在組成物中加入甜味劑。此等包括糖精、右旋糖、蔗糖、乳糖、木糖醇、麥芽糖、果糖、阿斯巴甜、環己基胺基磺酸鈉、D-色胺酸、二氫查爾酮、乙醯磺胺酸及其混合物。亦可將各種著色劑掺入到本發明中。甜味劑和著色劑在牙膏中的使用含量通常從0.005%至约5%,以組成物的重量為基準。
草本試劑(包括但不限於黃連萃取物、金銀花萃取物及其混合物)也能夠以0.01%至0.05%的含量存在於本文的組成物中。據信此種草本試劑提供抗菌效力。亦可再加入0.01%至2%的多酚。較佳的多酚為茶多酚。
亦可將有效量的脫敏劑掺入到本發明的組成物中。脫敏劑選自:鹼金屬鹽(帶有II族金屬或鋁的氯化物、硝酸鹽、硫酸鹽或乙酸鹽,或可聚合單體,以堵塞細管)、鹼金屬或硝酸銨、草酸銨、檸檬酸和檸檬酸鈉。較佳的鹽為硝酸鉀、檸檬酸鉀及其混合物。此種脫敏劑公開於例如美國專利號5,718,885。
可進一步將Plasdone S-630或鋁水合物等去污劑加入到組成物。Plasdone為聚乙烯吡咯啶酮,其可藉由將乙烯吡咯啶酮聚合而合成。商業上將其製造成平均分子量為10,000至700,000的產品系列。在此,較佳為低分子量和中分子量(從10,000至100,000)。為了有效移除污垢,聚乙烯吡咯啶酮含量較佳為從0.5%至10%,較佳為從1.0%至7.0%,甚至更佳為從1.5%至5.0%。
本發明的組成物選擇性包含營養素。適合的營養素包含維他命、礦物質、L-精胺酸等胺基酸,及其混合物。維他命包含維他命C、維他命D、硫胺素(thiamine)、核黃素(riboflavin)、泛酸鈣(calcium pantothenate)、菸酸(niacin)、葉酸、菸鹼醯胺(nicotinamide)、比哆醇(pyridoxine)、氰鈷胺(cyanocobalamin)、對氨基苯酸、生物類黃酮(bioflavonoid)及其混合物。營養補充品包括胺基酸(例如L-色胺酸、L-賴胺酸、甲硫胺酸、羥丁胺酸、左卡尼汀(levocarnitine)和L-卡尼丁)、抗脂肪肝劑(lipotropics)(例如膽鹼、肌醇、甜菜鹼和亞麻油酸)及其混合物。
已知上述每一類別的材料之一般性質可能不同,但是仍有可能具備共同性質,且任何特定材料可提供兩種或多種此類型材料的功效。組成物中的所有成分可具有主要功能以外的功用,且可構成組成物整體性質的一部份,包括穩定性、功效、相容性、口感和氣味等。較佳為所選的載體材料可與組成物的其他成分相容。
本發明的產品形式之一種類型為潔齒劑。「潔齒劑」一詞通常指用於清潔口腔表面的配方。潔齒劑並非用於吞嚥以便系統地提供治療、而是施加至口腔的一種口用組成物,在治療口腔後
會被吐出。一般使用潔齒劑時,會搭配牙刷等清潔用具,通常會將潔齒劑施加到牙刷毛上,然後使用牙刷刷洗可接觸的口腔表面。較佳為潔齒劑呈膏狀或膠狀(或其組合)。
本發明的口腔保健組成物通常呈單相。然而,在部分實施方式中,組成物呈物理分離,方法是例如採用雙層包裝。潔齒劑組成物可為膏狀、膠狀或其任何組態或組合。本發明的另一實施方式包含雙相或多相組成物,其包含其他潔齒劑組成物以進一步提升穩定性、功效及/或潔齒劑產品的美觀。例如,雙相組成物可包含:第一相,包含具有聚磷酸鹽和離子活性劑的本文低水組成物;分離的第二相,包含其他活性劑,例如漂白劑,較佳為過氧化物源,或牙齒表面調節劑,以提供增進的清潔、美白、抗污垢和口感。牙齒調節劑的實例為聚矽氧烷和改質的聚矽氧烷,包括二有機聚矽氧烷,例如聚二甲基矽氧烷;烷基和烷氧基二甲基矽氧烷共聚醇,例如C12至C20烷基二甲基矽氧烷共聚醇;及胺基烷基矽氧烷。此等矽氧烷聚合物例如公開於美國專利號5,759,523;6,024,891;6,123,950;6,019,962;及6,139,823。
潔齒劑組成物的分配器可為軟管、抽吸裝置或適用於分配牙膏的任何容器。在雙相口腔組成物中,每種口腔組成物會被裝在分配器中物理分隔的腔室內,分配時會彼此相靠。
使用方式
在執行實施方式時,使用者只需要將本文的口腔保健組成物施加至人類或動物的牙齒表面所需區域,即可獲得所需成效,例如減少或預防牙菌斑、美白、口氣清新、預防齲齒、減輕疼痛、增進牙齦健康、抑制牙結石、抑制侵蝕等。已知使用潔齒劑可抑制
牙齒表面的侵蝕,或預防去礦物質作用,如美國專利號6,685,920所開。亦可將組成物施加至其他口腔表面,例如齒齦或黏膜組織,然而,據信將潔齒劑組成物施加至牙齒上可獲得最佳成效。潔齒劑組成物可直接或間接接觸牙齒及/或口腔表面,然而,較佳為直接施加潔齒劑組成物。可藉由任何方式施加潔齒劑組成物,但較佳為使用牙刷或藉由潔齒劑漿狀物進行潤濕再施加。施用次數為每日最少一次,然而,較佳為每日五次,且持續一段時間,例如一週至一年、至三年或一生。
製造本發明的口腔組成物時,可採用製造此種組成物的多種標準技術之任一種。例如,潔齒劑的製造方法已為人所知,如美國專利號3,966,863;美國專利號3,980,767;美國專利號4,328,205;及美國專利號4,358,437等述。為了製造潔齒劑,可準備裝載保濕劑(例如甘油、山梨糖醇及丙二醇、增稠劑和抗菌劑,例如三氯沙)的容器,並加入陰離子和兩性系界面活性劑的混合物,然後摻入預先混合的研磨劑及氯鹽。最後,混合調味劑,且將pH調整成6.8至7.0。
本發明的部分實施方式提供一種口腔保健組成物(組成物1),包含:(a)口腔可接受載體;(b)氟離子源;(c)錫離子源;(d)不可溶鋅離子源;(e)緩衝系統,包含檸檬酸,其中檸檬酸含量至少為組成物的1重量%;及
其中組成物具有低於15重量%的總水含量,例如:
1.1組成物1,其中檸檬酸含量為0.5-4重量%或1-3重量%,或1.1-1.5重量%或1.8-2.2重量%,或1.3重量%至2重量%;
1.2任何上述組成物,其中不可溶鋅離子源包含有機酸的鋅鹽;
1.3任何上述組成物,其中不可溶鋅離子源包含氧化鋅、磷酸鋅、焦磷酸鹽或其混合物;
1.4任何上述組成物,其中氯離子源選自氯化亞錫、氯化鈉、氯化鉀、單氯磷酸鈉、氯矽酸鈉、氯矽酸銨、氯化胺(例如N'-十八基三甲烯二胺-N,N,N'-三(2-乙醇)-二氫氟)、氟化銨、氟化鈦、六氟硫酸鹽及其組合;
1.5任何上述組成物,其中氟化亞錫源選自氟化亞錫、二水合氯化亞錫、乙酸亞錫、酒石酸亞錫、檸檬酸亞錫鈉或其混合物;
1.6任何上述組成物,其中氟離子源亞錫離子源包含氟化亞錫;
1.7任何上述組成物,包含至少一種聚磷酸鹽,選自具有三個或以下磷原子的無機焦磷酸鹽;
1.8組成物1.5,其中至少一種焦磷酸鹽選自焦磷酸四鈉、三焦磷酸鈉及其混合物;其中焦磷酸鹽總含量佔組成物的1至10重量%;
1.9任何上述組成物,其中緩衝系統包含檸檬酸和檸檬酸三鈉的混合物;
1.10任何上述組成物,包含具有經交聯聚乙烯吡咯啶酮及膠(結合形式)的增稠劑;
1.11任何上述組成物,包含增稠劑,其包含纖維素、氧化乙烯和氧化丙烯的合成嵌段聚合物或其混合物;
1.12任何上述組成物,其中鋅離子源含量從0.1至2重量%,或從0.5%
至1.5重量%,或從0.9%至1.1重量%;
1.13任何上述組成物,其中亞錫離子源含量從0.05%至5重量%,或從0.1%至1重量%,或從0.35%至0.55重量%;
1.14任何上述組成物,其中氟離子源含量從0.1%至5%,或從0.2%至1%,或從0.3至0.6%,以組成物總重量為基準;
1.15任何上述組成物,其中組成物的總水含量低於20%,或低於15%,或從低於15%至高於10重量%,以組成物的重量為基準;
1.16任何上述組成物,其中結合的金屬離子源含量佔組成物重量從0.15%至7%,或從0.6%至2.5%,或從1.25%至1.65%;
1.17任何上述組成物,包含甲基乙烯基醚/馬來酸酐共聚物,其平均分子量為30,000至1,000,000,例如300,000至800,000;
1.18任何上述組成物,包含游離形式或口腔可接受鹽類形式的L-精胺酸;
1.19任何上述組成物,包含其他緩衝劑,例如磷酸鈉緩衝劑(例如單鹼磷酸鈉和磷酸二鈉);
1.20任何上述組成物,包含保濕劑,例如選自山梨糖醇、丙二醇、聚乙二醇、木糖醇及其混合物;
1.21任何上述組成物,包含研磨劑或粒狀物;
1.22上述組成物,其中研磨劑或粒狀物選自重碳酸鈉、磷酸鈣(例如二水合磷酸二鈣)、硫酸鈣、沈澱的碳酸鈣、二氧化矽(例如水合二氧化矽)、氧化鐵、氧化鋁、珍珠岩、聚乙烯等塑膠粒子及其組合;
1.23任何上述組成物,包含佔組成物總重量15重量%至70重量%的研磨劑含量;
1.24任何上述組成物,包含一種或多種界面活性劑,例如選自陰離
子、陽離子、兩性離子、非離子界面活性劑及其混合物,例如包含一種陰離子界面活性劑,例如一種界面活性劑,選自月桂基硫酸鈉、乙醚硫酸鈉及其混合物,其含量例如為0.3重量%至4.5重量%。
1.25任何上述組成物,進一步包含一種或多種聚合物,選自聚乙二醇、多醣(舉例而言,例如纖維素衍生物,羧甲基纖維素、三仙膠或卡拉膠等多醣膠)及其混合物。
1.26任何上述組成物,包含一種或多種抗菌劑,例如包含選自以下項目的抗菌劑:鹵化二苯基醚(例如三氯沙)、草本萃取物和精油(例如迷迭香萃取物、茶萃取物、木蘭萃取物、百里酚(thymol)、薄荷腦(menthol)、桉油精(eucalyptol)、香葉草醇(geraniol)、香旱芹酚(carvacrol)、檸檬醛(citral)、日檜醇(hinokitol)、兒茶酚(catechol)、水楊酸甲酯(methyl salicylate)、表沒食子兒茶素沒食子酸酯(epigallocatechin gallate)、表沒食子兒茶素(epigallocatechin)、沒食子酸(gallic acid)、米斯瓦克(miswak)萃取物、酸刺(sea-buckthorn)萃取物、雙胍類消毒劑(例如洛赫西定(chlorhexidine)、阿來西定(alexidine)或奧替尼啶(octenidine))、四級銨化合物(例如氯化鯨蠟吡啶(cetylpyridinium chloride))、氯化烷基二甲基苄基銨(benzalkonium chloride)、氯化十四基吡啶陽離子(tetradecylpyridinium chloride)、N-十四基-4-乙基氯化吡啶鐵(N-tetradecyl-4-ethylpyridinium chloride)、酚消毒劑、海克替啶(hexetidine)、奥替尼啶(octenidine)、血根鹼(sanguinarine)、優碘(povidone iodine)、地莫匹醇(delmopinol)、salifluor)、金屬離子(例如鋅鹽,例如檸檬酸鋅、亞錫鹽、銅鹽、鐵鹽)、血根鹼(sanguinarine)、蜂膠(propolis)和產氧劑(例如過氧化氫、緩衝的過氧硼酸鈉或過氧碳酸)、苯二甲酸及其鹽類、
單苯二甲酸及其鹽類、硬脂酸抗壞血酸酯(ascorbyl stearate)、油醯基肌胺酸(oleoyl sarcosine)、烷基硫酸鹽、磺基琥珀酸鈉二辛酯(dioctyl sulfosuccinate)、水楊醯苯胺(salicylanilide)、溴化多米芬(domiphen bromide)、地莫匹醇(delmopinol)、辛哌醇(octapinol)和其他N-六氫吡啶基(piperidino)衍生物、尼生素(nisin)製造、亞氯酸鹽及上述任何項目之混合物,例如包含三氯沙和氯化鯨蠟吡啶(cetylpyridinium chloride);
1.27任何上述組成物,包含一種美白劑,例如選自過氧化物、亞氯酸金屬鹽、過硼酸鹽、過碳酸鹽、過氧酸、次氯酸鹽及其組合;
1.28任何上述組成物,進一步包含過氧化氫、過氧化氫源,例如過氧化脲、過氧化鹽或複合物(例如過氧磷酸鹽、過氧碳酸鹽、過硼酸鹽、過氧矽酸鹽或過硫酸鹽;例如,過氧磷酸鈣、過硫酸鉀);
1.29任何上述組成物,進一步包含鈣和磷酸鹽源,選自(i)鈣玻璃複合物,例如磷矽酸鈉鈣;及(i)鈣蛋白質複合物,例如酪蛋白磷酸胜肽-不定形磷酸鈣;
1.30任何上述組成物,進一步包含可溶鈣鹽,例如選自硫酸鈣、氯化鈣、硝酸鈣、醋酸鈣、乳酸鈣及其組合;
1.31任何上述組成物,進一步包含生理或口腔可接受鉀鹽,例如硝酸鈣或氯化鉀,其含量設成足以減少牙齒敏感度;
1.32任何上述組成物,其形式為潔齒劑,例如牙膏,例如清潔凝膠或半透明牙膏;
1.33任何上述組成物,其形式為單相;
1.34任何上述組成物,包含一種或多種含量如下的成分:
1.35任何上述組成物,其不包含甲基乙烯基醚-馬來酸酐共聚物;
1.36一種治療或預防口腔疾病或症狀的方法,包含採用如任何上述組成物以接觸有需要的病患口腔表面;
1.37如上述申請專利範圍的方法,該方法用於治療和預防細菌牙菌斑累積或預防牙齒侵蝕。
以下實例進一步本說明較佳的實施方式,但應理解本發明並不限於此。
程序
準備4種配方,成分如配方A中標示,其中羧甲基纖維素、檸檬酸、焦磷酸四鈉、焦磷酸鈉酸、三焦磷酸鈉含量如表1和表2所示變化。
決定配方中水溶性錫和水溶性鋅的含量時,可採用火焰式原子吸收光譜儀。可使用裝配有空氣-乙炔焊炬和氘背景校正裝
置的合適雙光束原子吸收分光光度計,例如Varian SpectrAA 220FS。另外,亦可使用鋅空心陰極燈和AA級乙炔燈。將樣品以水稀釋後,使用火焰式原子吸收光譜儀量測出組成物中水溶性鋅和水溶性錫,再與鋅或錫標準值比較。將部分配方分散在水中,將所得溶液移到容量瓶,以水稀釋後進行離心處理。使用原子吸收光譜儀偵測上層液中的錫或鋅,然後比較樣品溶液的吸收度和已知鋅或錫濃度的外部校正標準之吸收度。若要決定錫或鋅的總含量,則不將樣品分散在水中,而是使用合適的酸混合物(例如氫氯酸、硝酸及/或氫氟酸)以蒸汽浴溶解樣品。
將配方以40℃熟化13週。在不同時間點決定錫總含量、鋅總含量、水溶性錫和水溶性鋅含量。
結果
對照實例-在較早的配方中有可溶性鋅源(2重量%檸檬酸鋅)和0.454重量%氟化亞錫,其中包含0.6重量%檸檬酸/3.0重量%檸檬酸三鈉。此配方原先僅具有0.39重量%的可溶性鋅初始含量,並在12週熟成後略微降低至0.34重量%。亞錫含量從初始溶解至12週熟成結束期間皆維持穩定(範圍從0.31重量%至0.36重量%)。
令人驚訝的是,在含或不含CMC的配方中,若具有相同含量(0.454%)的氟化亞錫且較少含量(1重量%)的可溶鋅源(ZnO),則會在所使用檸檬酸含量高於1重量%(範圍從0.62重量%至0.69重量%)時顯示較高的初始溶解度,且此高溶解度在13週熟成(0.55重量%至0.63重量%)後亦會維持。
此外,當檸檬酸含量增加到2%,可溶性亞錫的初始含量和13週熟成後含量(0.32重量%至0.35重量%)如同對照實例中量測到的範圍。
熟習相關技術之人士應知悉,本實施方式可在不偏離本發明精神的範圍內進行多種變更和修改。所有此種變更皆意圖落在隨附申請專利範圍內。
Claims (21)
- 一種口腔保健組成物,在單相中包含:(a)口腔可接受載體;(b)氟離子源;(c)錫離子源;(d)不可溶鋅離子源;(e)緩衝系統,包含檸檬酸,其中檸檬酸含量至少為組成物的1重量%;及其中組成物具有低於15重量%的總水含量,以組成物重量為基準。
- 如申請專利範圍第1項的組成物,其中該檸檬酸含量為0.5-4重量%或1-3重量%,或1.1-1.5重量%或1.8-2.2重量%,以組成物重量為基準。
- 如任何前述申請專利範圍的組成物,其中該檸檬酸含量為1-3重量%,以組成物重量為基準。
- 如任何前述申請專利範圍的組成物,其中該檸檬酸含量為1.1-1.5重量%,以組成物重量為基準。
- 如申請專利範圍第1至3項中任一項的組成物,其中該檸檬酸含量為1.8-2.2重量%,以組成物重量為基準。
- 如前述申請專利範圍中任一項的組成物,其中該不可溶鋅離子源包含有機酸的鋅鹽。
- 如申請專利範圍第3項的組成物,其中該不可溶鋅離子源包含氧化鋅、磷酸鋅、焦磷酸鹽或其混合物。
- 如前述申請專利範圍中任一項的組成物,其中該氟離子源及錫 離子源包含氟化錫。
- 如前述申請專利範圍中任一項的組成物,其中至少一焦磷酸鹽選自具有三個或以下磷原子之無機焦磷酸鹽類。
- 如申請專利範圍第6項的組成物,其中該至少一焦磷酸鹽選自焦磷酸四鈉、三焦磷酸鈉及其混合物,其中焦磷酸鹽總含量為組成物的1至10重量%。
- 如前述申請專利範圍中任一項的組成物,其中該緩衝系統包含檸檬酸和檸檬酸三鈉的混合物。
- 如前述申請專利範圍中任一項的組成物,其中包含聚乙烯吡咯烷酮、樹膠或其混合物。
- 如前述申請專利範圍中任一項的組成物,其中包含改質纖維素,例如羧甲基纖維素。
- 如前述申請專利範圍中任一項的組成物,其中包含至少一保濕劑,選自以甘油、聚乙二醇、聚丙二醇及其混合物所構成之群組。
- 如前述申請專利範圍中任一項的組成物,其中該組成物為潔齒劑,包含一或多項研磨劑、界面活性劑、泡沫劑、維他命、聚合物、潔白劑、酶、保濕劑、增稠劑、抗菌劑、防腐劑、L-精胺酸、調味劑或著色劑。
- 如前述申請專利範圍中任一項的組成物,其係單相形式。
- 一種口腔保健組成物,包含:(a)0.5-3重量%檸檬酸;(b)0.5-10重量%檸檬酸三鈉;(c)0.1-5重量%氧化鋅; (d)0.1-5重量%氟化亞錫;(e)10-50重量%甘油;(f)1-25重量%丙二醇;選擇性包含一或多項:(g)0.1-12重量%三仙膠;(h)0.25-10重量%聚乙烯吡咯烷酮;(i)0.2-1.5重量%羧甲基纖維素;(j)5-60重量%二氧化矽(總含量);(k)0.1-10重量%焦磷酸四鈉;(l)0-5重量%焦磷酸鈉酸;(m)0.1-10重量%三焦磷酸鈉;(n)0.1-10重量%月桂基硫酸鈉;(o)0.1-10重量%烷基醯胺甜菜鹼。
- 如申請專利範圍第17項的組成物,其中包含:(a)1.1-1.5重量%或1.8-2.2重量%檸檬酸;(b)2-4重量%檸檬酸三鈉;(c)0.5-2重量%氧化鋅;(d)0.1-2重量%氟化錫;(e)10-50重量%甘油;(f)2-10重量%聚丙二醇;選擇性包含一或多項:(g)0.1-0.5重量%三仙膠;(h)0.25-10重量%聚乙烯吡咯烷酮;(i)0.3-0.9重量%羧甲基纖維素; (j)10-40重量%二氧化矽(總含量);(k)1-4重量%焦磷酸四鈉;(l)0.5-1.5重量%焦磷酸鈉酸;(m)1-4重量%三焦磷酸鈉;(n)1.2-2.5重量%月桂基硫酸鈉;(o)0.5-2重量%烷基醯胺甜菜鹼。
- 如申請專利範圍第18項的組成物,其中包含:(a)1.1-1.5重量%或1.8-2.2重量%檸檬酸;(b)2.9-3.1重量%檸檬酸三鈉;(c)0.9-1.1重量%氧化鋅;(d)0.4-0.6重量%氟化錫;(e)10-50重量%甘油;(f)6-8重量%聚丙二醇;選擇性包含一或多項:(g)0.275-0.325重量%三仙膠;(h)0.25-10重量%聚乙烯吡咯烷酮;(i)0.65-0.75重量%羧甲基纖維素;(j)22-26重量%二氧化矽(總含量);(k)1.75-2.25重量%焦磷酸四鈉;(l)0.9-1.1重量%焦磷酸鈉酸;(m)2.75-3.25重量%三焦磷酸鈉;(n)1.5-3.25重量%月桂基硫酸鈉;(o)1.5-1.75重量%烷基醯胺甜菜鹼。
- 一種治療或預防口腔疾病或症狀的方法,包含使如上述申請專 利範圍中任一項之組成物接觸有需要的病患之口腔表面。
- 如申請專利範圍第20項的方法,其中該口腔疾病或症狀為生物薄膜形成、牙菌斑形成、口腔發炎或其組合。
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CN106572951B (zh) | 2014-08-08 | 2020-09-29 | 高露洁-棕榄公司 | 牙齿色斑去除和预防 |
CA2979333C (en) | 2015-10-08 | 2023-08-29 | Colgate-Palmolive Company | Oral care compositions and methods of using the compositions |
MX370966B (es) | 2015-12-30 | 2020-01-10 | Colgate Palmolive Co | Composiciones para el cuidado bucal. |
US10123952B2 (en) | 2015-12-30 | 2018-11-13 | Colgate-Palmolive Company | Personal care compositions |
US10292912B2 (en) | 2015-12-30 | 2019-05-21 | Colgate-Palmolive Company | Personal care compositions |
CA3009516A1 (en) | 2015-12-30 | 2017-07-06 | Colgate-Palmolive Company | Oral care compositions |
BR112018075162B1 (pt) * | 2016-06-24 | 2022-03-22 | Colgate-Palmolive Company | Composições para higiene bucal e usos relacionados |
AU2016410613B2 (en) * | 2016-06-24 | 2019-08-15 | Colgate-Palmolive Company | An oral care composition |
BR112018005749B1 (pt) * | 2016-06-24 | 2022-06-21 | Colgate-Palmolive Company | Composição para cuidado oral |
US10278906B2 (en) | 2016-06-24 | 2019-05-07 | Colgate-Palmolive Company | Oral care compositions |
BR112018015792B1 (pt) * | 2016-06-24 | 2023-03-28 | Colgate-Palmolive Company | Composições para higiene bucal e uso de um carreador oralmente aceitável, fosfato de zinco e fluoreto estanoso |
CA3045783A1 (en) * | 2016-12-21 | 2018-06-28 | Colgate-Palmolive Company | Oral care compositions comprising salicylamide |
MX2019007187A (es) | 2016-12-21 | 2019-09-05 | Colgate Palmolive Co | Composiciones para el cuidado bucal. |
AU2017379612B2 (en) | 2016-12-21 | 2020-02-20 | Colgate-Palmolive Company | Oral care compositions |
US10285919B2 (en) | 2016-12-21 | 2019-05-14 | Colgate-Palmolive Company | Oral care compositions |
CA3044403A1 (en) | 2016-12-21 | 2018-06-28 | Colgate-Palmolive Company | Oral care compositions and methods of use |
RU2723646C1 (ru) * | 2016-12-21 | 2020-06-17 | Колгейт-Палмолив Компани | Композиции для ухода за полостью рта |
BR112019012472B1 (pt) * | 2016-12-21 | 2022-11-08 | Colgate-Palmolive Company | Composição para higiene bucal compreendendo fonte de zinco, fonte estanosa e fonte de fluoreto |
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JP7058342B2 (ja) | 2018-03-29 | 2022-04-21 | ザ プロクター アンド ギャンブル カンパニー | 歯肉健康を促進するための口腔ケア組成物 |
CA3095054C (en) | 2018-03-29 | 2023-05-02 | The Procter & Gamble Company | Oral care compositions comprising a stannous ion source and an amino acid for promoting gum health |
CA3095048C (en) | 2018-03-29 | 2023-07-11 | The Procter & Gamble Company | Oral care compositions comprising a stannous ion source and a neutral amino acid for promoting gum health |
CN113271911A (zh) | 2018-12-26 | 2021-08-17 | 高露洁-棕榄公司 | 口腔护理组合物 |
CN109568218B (zh) * | 2019-01-30 | 2021-12-17 | 浙江康佰裕生物科技有限公司 | 美容液体敷料 |
EP4003279A1 (en) * | 2019-08-27 | 2022-06-01 | Colgate-Palmolive Company | Zinc phosphate containing compositions |
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WO2021175577A1 (en) * | 2020-03-03 | 2021-09-10 | Unilever Ip Holdings B.V. | Transparent dentifrice comprising zinc |
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JP2022094030A (ja) * | 2020-12-14 | 2022-06-24 | ライオン株式会社 | 口腔用組成物 |
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2014
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- 2014-06-20 WO PCT/US2014/043427 patent/WO2015195140A1/en active Application Filing
- 2014-06-20 EP EP14737482.1A patent/EP3157638B1/en active Active
- 2014-06-20 MX MX2016015772A patent/MX359754B/es active IP Right Grant
- 2014-06-20 AU AU2014398221A patent/AU2014398221B2/en active Active
- 2014-06-20 CN CN201480079726.7A patent/CN106470737B/zh active Active
- 2014-06-20 RU RU2016149576A patent/RU2679416C2/ru active
- 2014-06-20 US US15/319,636 patent/US10154948B2/en active Active
- 2014-06-20 CA CA2952921A patent/CA2952921C/en active Active
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2015
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- 2015-06-19 AR ARP150101982A patent/AR100925A1/es unknown
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2016
- 2016-10-19 ZA ZA2016/07202A patent/ZA201607202B/en unknown
- 2016-11-28 IL IL249262A patent/IL249262A0/en unknown
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2018
- 2018-11-02 US US16/178,788 patent/US20190133903A1/en not_active Abandoned
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EP3157638B1 (en) | 2018-08-08 |
RU2016149576A3 (zh) | 2018-07-23 |
RU2016149576A (ru) | 2018-07-23 |
MX359754B (es) | 2018-10-01 |
WO2015195140A1 (en) | 2015-12-23 |
BR112016028403A2 (pt) | 2018-06-26 |
US20190133903A1 (en) | 2019-05-09 |
US20170319447A1 (en) | 2017-11-09 |
CA2952921C (en) | 2021-06-15 |
AR100925A1 (es) | 2016-11-09 |
EP3157638A1 (en) | 2017-04-26 |
CA2952921A1 (en) | 2015-12-23 |
CN106470737A (zh) | 2017-03-01 |
RU2679416C2 (ru) | 2019-02-08 |
US10154948B2 (en) | 2018-12-18 |
AU2014398221B2 (en) | 2017-10-05 |
IL249262A0 (en) | 2017-02-28 |
BR112016028403B1 (pt) | 2020-12-15 |
CN106470737B (zh) | 2020-02-14 |
MX2016015772A (es) | 2017-02-27 |
AU2014398221A1 (en) | 2016-12-15 |
ZA201607202B (en) | 2019-12-18 |
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