CN1160050C - 低涩味脱敏牙用组合物 - Google Patents

低涩味脱敏牙用组合物 Download PDF

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CN1160050C
CN1160050C CNB988060574A CN98806057A CN1160050C CN 1160050 C CN1160050 C CN 1160050C CN B988060574 A CNB988060574 A CN B988060574A CN 98806057 A CN98806057 A CN 98806057A CN 1160050 C CN1160050 C CN 1160050C
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castor oil
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S·W·费舍尔
E·A·塔夫斯
Լ���ǿ�
M·T·约兹亚克
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R·J·加姆波吉
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Colgate Palmolive Co
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    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61QSPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q11/00Preparations for care of the teeth, of the oral cavity or of dentures; Dentifrices, e.g. toothpastes; Mouth rinses
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00Cosmetics or similar toiletry preparations
    • A61K8/18Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/19Cosmetics or similar toiletry preparations characterised by the composition containing inorganic ingredients
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00Cosmetics or similar toiletry preparations
    • A61K8/18Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/92Oils, fats or waxes; Derivatives thereof, e.g. hydrogenation products thereof
    • A61K8/922Oils, fats or waxes; Derivatives thereof, e.g. hydrogenation products thereof of vegetable origin
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P27/00Drugs for disorders of the senses
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P29/00Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2800/00Properties of cosmetic compositions or active ingredients thereof or formulation aids used therein and process related aspects
    • A61K2800/80Process related aspects concerning the preparation of the cosmetic composition or the storage or application thereof
    • A61K2800/88Two- or multipart kits

Abstract

公开了一种双组分脱敏牙用组合物,其中包括含脱敏用钾盐如硝酸钾的第一牙用组分,以及含亚锡盐脱敏剂如氟化亚锡的第二牙用组分,两组分彼此分装,直至应用于过敏性牙齿前混合分配,至少一个牙用组分中含有氢化蓖麻油的氧乙基化反应产物,用于降低用户使用该混合产品时感到的涩味口感。

Description

低涩味脱敏牙用组合物
发明领域
本发明涉及含有钾盐和亚锡盐的脱敏牙用组合物,用于降低与牙过敏有关的不适和疼痛,本发明尤其涉及含有低涩味的亚锡盐和钾盐的双组分脱敏牙用组合物。
背景技术
牙过敏是指对牙质表面所受的热量(热或冷)、渗透、触觉等物理刺激以及对裸露牙质所受的热量、渗透和触觉刺激所产生的急性局部牙痛反应。牙质裸露通常是由于牙床萎缩、牙釉质损耗造成的,常会导致牙过敏。
已知亚锡盐如氟化亚锡具有减轻牙过敏的功效。本领域还已知钾盐能有效地治疗牙过敏。例如在美国专利3863006中公开了可加入脱敏牙膏的钾盐,如硝酸钾。
在申请日为1996年2月2日的共同待审申请SN 08/594605中公开了一种牙用脱敏组合物,其中包括分装的第一牙用组分和第二牙用组分,直到同时涂敷在牙齿上时才相互混合,其中第一组分中含有脱敏用钾盐,如硝酸钾,第二组分中含有亚锡盐脱敏剂。
尽管牙用产品中同时应用亚锡盐和钾盐能有效治疗牙过敏,但使用该牙用产品时,其中的亚锡盐和钾盐会产生涩、酸、苦的口味,这会令需要牙齿脱敏治疗的用户却步。因此,需要一种能改善含亚锡盐和钾盐牙膏涩味的方法,以使其更为宜人。
发明内容
本发明提供了一种用于治疗牙过敏的低涩味牙用组合物,其中包括分装的牙用组分,包括亚锡盐或钾盐,其中通过采用至少约6%(重量)的氧乙基化氢化蓖麻油来降低涩味。
如下文所述,牙用组分中的氧乙基化氢化蓖麻油能在用户使用时令牙膏的涩味基本降低,具有改进的口味。
具体实施方式
氧乙基化氢化蓖麻油是已知组合物,例如可通过由约40-60mol环氧乙烷与1mol氢化蓖麻油反应制得。该组合物由BadischeAnilin-und Sodafabrick(Federal Republic of Germany德意志联邦共和国)以商品名Cremophor销售。
氧乙基化氢化蓖麻油已在含亚锡盐的口用护理产品中被用作乳化剂。例如在美国专利428822中公开了将CremophorRH(即含0.1%(重量)氧乙基化甘油的氢化蓖麻油脂肪酸酯)在含有氟化亚锡的漱口剂中用作乳化剂。
本发明中,将至少约6%(重量)、优选约6-8%(重量)的氧乙基化氢化蓖麻油加入含有亚锡盐或钾盐的牙用组分中能有效降低涩味。应避免氧乙基化氢化蓖麻油的用量高于约8%(重量),因为该用量会破坏产品的流变学特性,使其不适用于用户。
如下文所述,若用量低于约6%(重量)的氧乙基化氢化蓖麻油对用户感到的涩味口感的降低作用则非常有限。
欧洲专利251542中公开的聚氧化乙烯氢化蓖麻油能有效降低牙用产品中锌盐的涩味,其中聚氧化乙烯氢化蓖麻油在牙用组合物中的用量为0.1-5%(重量),优选0.3-4%(重量)。欧洲专利还提出当用于牙用组合物中的聚氧化乙烯氢化蓖麻油的用量高于5%(重量)时,聚氧化乙烯氢化蓖麻油会产生不适的油质感。
在实施本发明时,脱敏用钾离子源一般是水溶性钾盐,其中包括硝酸钾、柠檬酸钾、氯化钾、碳酸氢钾和草酸钾,优选为硝酸钾。本发明组合物中钾盐的用量一般约为8-12%(重量),优选约为3-10%(重量)。
制备本发明的钾盐脱敏牙用组分时,将钾盐成分加入含有载体的牙用产品中,载体中包含水、保湿剂、表面活性剂和磨料。
保湿剂一般是保湿剂的混合物,如甘油、山梨醇和分子量为200-1000的聚乙二醇的混合物,其它保湿剂的混合物及单独使用的保湿剂也适用。保湿剂的含量约为10-80%(重量),优选约为40-50%(重量)。水含量约为10-20%(重量)。
含钾盐的牙用组分中可包含无机增稠剂,其中包括煅制二氧化硅,如购自Cabot公司的Cabosil,以及增稠用二氧化硅,包括购自Crosfield Chemicals的名为Sorbosil TC-15的产品或购自W.R.Grace的Sylox 15。
本发明的含钾盐成分的牙用组分中还可包含天然和合成胶的有机增稠剂。这类增稠剂实例有:角叉菜胶(爱尔兰苔)、黄原胶、羧甲基纤维素钠、淀粉、聚乙烯基吡咯烷酮、羟乙基丙基纤维素、羟丁基甲基纤维素、羟丙基甲基纤维素,以及羟乙基纤维素。本发明组合物中有机增稠剂的用量约为0.1-3%(重量),优选约为0.5-1%(重量)。
适用于含脱敏用钾盐的牙用产品中的表面活性剂用于提供发泡特性。表面活性剂优选是阴离子表面活性剂,适用的实例包括高级烷基硫酸盐,其中如优选月桂基硫酸钾或月桂基硫酸钠,高级脂肪酸单甘酯单硫酸盐,如氢化椰子油脂肪酸单甘酯单硫酸盐,烷芳基磺酸盐,如十二烷基苯磺酸钠,高级脂肪磺基乙酸盐,1,2-二羟基丙烷磺酸高级脂肪酸酯,以及低级脂族氨基羧酸化合物的基本饱和的高级脂族酰胺,如脂肪酸、烷基或酰基等中含12-16个碳原子的化合物。最后值得一提的酰胺的实例是N-月桂酰基肌氨酸,以及N-月桂酰基、N-豆蔻酰基或N-棕榈酰基肌氨酸的盐。含钾盐的牙用组合物中表面活性剂的用量一般约为0.5-5.0%(重量)。
本发明含钾盐的牙用组分中可含有磨料,该磨料优选是含硅材料,如二氧化硅。优选的二氧化硅是沉淀无定形水合二氧化硅,如由Crosfield Chemicals销售的Sorbosil AC-35,或由Huber公司销售的Zeodent 115和Zeodent 165,但其它磨料也适用,其中包括:偏磷酸钠、偏磷酸钾、磷酸三钙、二水合磷酸钙、无水磷酸二钙、焦磷酸钙、正磷酸镁、磷酸三镁、碳酸钙、碳酸氢钠、三水合氧化铝、硅酸铝、硅酸锆、煅烧氧化铝和膨润土。含钾盐脱敏牙用组分的组合物中磨料的用量一般约为2-40%(重量),优选5-20%(重量)。
本发明的含钾盐的脱敏组分中还可含有其它成分,包括颜料、甜味剂、矫味剂和防腐剂。在白色牙膏组合物中,颜料选用二氧化钛、金红石,其用量一般为0.5-1%(重量),优选0.75-1.25%(重量)。甜味剂一般为人造或合成甜味剂,用量一般为0.1-1%(重量),优选0.3-0.5%(重量)。矫味剂优选是椒样薄荷/薄荷醇混合香精,用量一般为0.5-2%(重量),优选0.5-1.5%(重量)。可采用适量F.D.& C级染料,以达到所需颜色。含钾盐的牙用产品中其它组分或辅剂的含量一般不超过10%(重量),一般低于5%(重量),也可低至0%(重量)。
在制备本发明含脱敏用钾盐的牙用组分时,将保湿剂和胶凝剂分散在常规分散器中,直至混合物形成外观光滑的膏浆,然后加水。可将该混合物加热至37.8-43.3℃,混合10-30分钟制成均质凝胶相。加入钾盐,混合20分钟或直至完全溶解。加入甜味剂和着色剂,混合20分钟。将混合物转入真空混合器中。然后加入磨料,在真空条件为666-13330帕斯卡、优选666-6660帕斯卡压力条件下,经10-30分钟高速混合,制得均质混合物。然后在该糊状混合物中加入表面活性剂和氧乙基化氢化蓖麻油,然后在666-6660帕斯卡真空条件下继续混合10-20分钟。所得的产品是稳定的脱敏牙用产品,其质地与常规的牙膏或牙用凝胶类似,其pH为5-8,优选6.5-7.5,例如为7,并且具有宜人的口味。
本发明中的含亚锡盐的牙用产品是本领域已知的。在美国专利5578293中公开了一种特别适用于本发明的含亚锡盐的牙用产品,所公开的内容结合在本发明中作为参考。美国专利5578293中公开了一种含水牙用产品,其中含有经稳定化的亚锡化合物,该牙用产品具有抗牙斑和牙石的功效,并且其中所含的含水载体中包括约10-25%(重量)水,以及约35-50%(重量)保湿剂,如甘油、山梨醇或其混合物。含水载体中约含0.05-2%(重量)可释放水溶性亚锡离子的化合物,如氟化亚锡和氯化亚锡,以及它们的混合物,约10-40%(重量)二氧化硅磨料,以及约0.05-2.0%(重量)水溶性碱金属焦磷酸盐(如焦磷酸四钠)与约0.01-10%(重量)多羧酸类食用级有机酸(如柠檬酸、柠檬酸钠或它们的混合物)的混合物,该用量足以对亚锡离子进行有效稳定化,组合物中含有有效量的稳定化亚锡离子,起到治疗性抗牙斑功效,本发明组合物中还含有有效量的焦磷酸盐,用于抗牙石。
制备含亚锡盐的牙用产品时,首先将亚锡盐加入一部分水或常用于制备牙用产品的保湿剂(如甘油、山梨醇或其混合物)中混合,可加热促进溶解,制备预混物。然后在常规混合器中将预混物与增稠剂(如黄原胶、羧甲基纤维素和它们的混合物)、甜味剂(如糖精钠)、有机酸性化合物(如柠檬酸)、焦磷酸盐磨料(如二氧化硅磨料)、染料或颜料一同分散在剩余的水、保湿剂中,直至形成具有光滑外观的浆状物。将混合物经10-30分钟加热至37.8-48.9℃,制成均质凝胶相。将该凝胶相转入真空混合器中,加入磨料,在真空条件为666-13330帕斯卡、优选666-6660帕斯卡条件下,经10-30分钟高速混合,制得均质糊状物。然后在该糊状混合物中加入表面活性剂(如月桂基硫酸钠)和氧乙基化氢化蓖麻油以及矫味剂,然后在666-6660帕斯卡真空条件下继续混合5-10分钟。所得的产品是稳定的牙用产品,具有常规的牙膏或牙用凝胶的质地,其pH为3-7,优选5.0-6.5,并且具有宜人的口味。
可采用任何能令钾盐与亚锡盐分装的方便的方法,以便装在同一包装内的两组分彼此不相接触而是可分装的。例如,可把单个包装容器划分成两室,分别盛装含氟化亚锡的牙用组分和含钾盐的组分,直至牙用时才混合。该两室容器是本领域已知的,例如在美国专利4211341、4687663、5085853、5186926中公开了两室套管,以及用于同时分散两种含活性成分的牙用组分的泵送装置。
采用以下实施例进一步说明本发明,但应理解的是其对本发明不构成任何限定。本说明书和权利要求书中的所有用量和百分比均以重量计。
实施例
两套双组分牙用产品分别称为第I套和第II套,其中一组分中含有一种或多种亚锡盐,另一组分中含有钾盐。按前述的方法制备I套和II套。各套中的双组分牙用产品的载体成分基本相同,除了其中作为本发明实施例的I套产品中在亚锡盐牙用组分中加入的氧乙基化氢化蓖麻油是通过将40mol环氧乙烷与氢化蓖麻油(购自BASF商品名为PEG 40蓖麻油)反应制得,而作为对照实施例的II套中,两牙用组分中均未加入蓖麻油化合物。
I套和II套产品中牙用组分的成分列于下表I和II中。I套和II套产品中独立的牙用组分分装在塑料牙膏包装管内的隔离两室中,其能以等体积分散。在40.6℃下经3个月贮存检验I套牙用双组分产品,与不含PEG40蓖麻油化合物的对照组II套牙用产品相比,含有PEG 40蓖麻油的I套双组分牙用产品从两室套管等体积量分配出时,发现含亚锡盐的牙用组分以及含钾盐的牙用组分的化学稳定性和美容稳定性均未受到影响。
由评估小组经单盲试验对I套和II套的双组分牙用产品的涩味和口味进行评估,其中由70名被测者用I套或II套牙用产品刷牙,得出涩味和口味适宜性等特性。
评估结果见下表III。该评估试验中,双组分牙用产品的平均特性比率越低,所感到的涩味、酸味和苦味越低。
                 表I
       I套双组分牙用产品组合物
成分 含亚锡盐的组分%(重量) 含硝酸钾的组分%(重量)
去离子水                                     19.600                             46.950无水柠檬酸                                   0.531                                -柠檬酸钠                                     2.657                                -氯化亚锡                                     0.600                                -氟化亚锡                                     0.908                                -PEG600                                       -                                   3.00硝酸钾                                       -                                   10.00甘油                                         24.240                              11.00黄原胶                                       0.400                               0.800CMC                                          0.300                               0.250山梨醇(70%)                                 19.064                               -糖精钠                                       0.400                               0.400TSPP                                         0.500                                -二氧化钛                                      -                                  0.200FD&C1号蓝(1%溶液)                           0.090                                -D&C10号黄(1%溶液)                           0.110                                -PEG 40蓖麻油                                 6.000                                6.000Zeodent 115                                  20.000                               22.000zeodent 165                                  2.200                                3.000矫味剂                                       0.900                                0.900月桂基硫酸钠                                 1.500                                1.500总量                                         100.000                              100.000
                  表II
       II套双组分牙用产品组合物
成分 含亚锡盐的组分%(重量) 含硝酸钾的组分%(重量)
去离子水                                                             19.600                                          46.950无水柠檬酸                                                           0.531                                           -柠檬酸钠                                                             2.657                                           -氯化亚锡                                                             0.600                                           -氟化亚锡                                                             0.908                                           -PEG 600                                                               -                                              3.00硝酸钾                                                                -                                              10.00甘油                                                                 24.240                                          11.00黄原胶                                                               0.300                                           0.800CMC12m31p                                                            0.300                                           0.250山梨醇NC(70%)                                                       25.564                                           -糖精钠                                                               0.400                                           0.400TSPP                                                                 0.500                                            -二氧化                                                                -                                              0.200FD&C 1号蓝(1%溶液)                                                  0.090                                           -D&C 10号黄(1%溶液)                                                  0.110                                           -Zeodent 115                                                          20.000                                          22.000zeodent 165                                                          1.8000                                          3.000矫味剂                                                               0.900                                           0.900月桂基硫酸钠                                                         1.500                                           1.500总量                                                                 100.000                                        100.000
                        表III
                   双组分牙用产品
口味特性                    I套              II套
涩味*                      3.2b            4.6a
酸味*                      3.9a            4.1a
苦味*                      3.6a            4.0a
*评估小组制定的强度等级:
等级:1=完全没有,3=轻微,5=中等,7=非常重,9=极重所记录具有不同的上标字母的数据是在90%置信度下明显不同,上标字母相同表示在统计学上并无明显不同,表现出相同趋势。
表III中记录的结果表明,通过将6%(重量)氢化蓖麻油加入双组分牙用产品中可明显降低常出现在含氟化亚锡的牙用产品中的涩味。
为进一步对照,重复实施例中的方法,但其中与牙用组分共用的氢化蓖麻油的用量有2-4%(重量)的不同。对涩味和口味评估的结果列于下表IV中。
                       表IV
亚锡盐牙用组分中  含硝酸钾的牙用组分  涩味  酸味   苦味氢化蓖麻油的含量  中氢化蓖麻油的含量(重量%)           (重量%)
      4%                 -           3.47  3.51   3.554%                 4%         3.22  3.51   3.336%                 -           3.45  3.58   3.426%                 6%         3.20  3.27   3.44-                   -           3.87  3.53   3.71
表IV所列结果表明:当双组分牙用产品中氢化蓖麻油的含量低于6%(重量),即为2-4%(重量)时,无法达到降低涩味的最佳效果。

Claims (8)

1.一种双组分脱敏牙用组合物,其中两组分彼此分装,但可从同一外包装中分配出来,该组合物由含有脱敏用钾盐的第一牙用组分、以及含有亚锡盐脱敏剂的第二牙用组分组成,所述第二组分中不含钾盐,所述第一组分中不含亚锡盐,并且其中至少一组分中包括氢化蓖麻油的氧乙基化反应产物,从而在将两组分分配并合并在一起使用时,牙用组合物中含有6-8重量%的氢化蓖麻油氧乙基化反应产物。
2.权利要求1的组合物,其中钾盐是硝酸钾。
3.权利要求1的组合物,其中亚锡盐是氟化亚锡。
4.权利要求1的组合物,其中氧乙基化氢化蓖麻油是环氧乙烷与氢化蓖麻油的反应产物。
5.氢化蓖麻油的氧乙基化反应产物在制备使用时可治疗牙过敏并且涩味口感降低的药物组合物中的用途,其中所述药物组合物包括含有脱敏用钾盐的第一牙用组分和含有亚锡盐的第二牙用组分,该第二组分中不含钾盐,该第一组分中不含亚锡盐,并且第一和第二牙用组分保持分装,其中至少一组分中包括氢化蓖麻油的氧乙基化反应产物,从而在将两组分分配并合并在一起使用时,牙用组合物中含有6-8重量%的氢化蓖麻油氧乙基化反应产物。
6.权利要求5的用途,其中钾盐是硝酸钾。
7.权利要求5的用途,其中亚锡盐是氟化亚锡。
8.权利要求5的用途,其中氧乙基化氢化蓖麻油是环氧乙烷与氢化蓖麻油的反应产物。
CNB988060574A 1997-05-14 1998-05-07 低涩味脱敏牙用组合物 Expired - Fee Related CN1160050C (zh)

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