CN101222909B - 包括厚朴提取物和表面活性剂的口气清新和口腔清洁产品 - Google Patents
包括厚朴提取物和表面活性剂的口气清新和口腔清洁产品 Download PDFInfo
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- CN101222909B CN101222909B CN2006800256492A CN200680025649A CN101222909B CN 101222909 B CN101222909 B CN 101222909B CN 2006800256492 A CN2006800256492 A CN 2006800256492A CN 200680025649 A CN200680025649 A CN 200680025649A CN 101222909 B CN101222909 B CN 101222909B
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Abstract
本申请公开了具有清洁口腔,清新口气和抗微生物益处的口腔用组合物,其包括厚朴提取物与表面活性剂的组合物。厚朴提取物在抑制口腔中生物膜的形成方面的效力通过口腔递送剂,如口香糖,糖果,锭剂,压制片和可食用膜中厚朴提取物与表面活性剂的协同组合而得到增强。
Description
相关美国申请
本申请是于2003年6月25日提交的美国专利申请10/606,671的部分继续,其要求于2002年6月25日提交的临时专利申请60/319,346的优先权。
技术领域
本发明大体上涉及糖果组合物,尤其涉及包含厚朴提取物的糖果组合物和制备该糖果组合物的方法。
发明背景
有相当多的消费者需要清新口气和杀死口腔细菌的产品。具有清新口气和杀细菌益处的口腔用产品是用于清洁口腔和清新口气的方便递送的产品。口腔中,尤其舌上的细菌可以产生挥发性硫化合物,这是引起口臭的主要原因。当然,清新口气是日常生活中非常重要的一部分。
为了促进正确的口腔卫生,应该在一天中重复进行清洁口腔和清新口气的操作。然而,根据所期望的清新口气的性质和必须进行口气清新的场所的不同,有时候清洁口腔和清新口气可能会较困难或不方便。用各种各样的装置和组合物刷牙,用牙线洁牙,清洁你的舌头和漱口是常见的很适合家庭私密性的口腔护理方法。但是,这些装置和组合物不太方便在家以外卫浴设施可能缺乏,不便或不卫生的地方使用。
牙菌斑是在刷牙较短时间内在牙齿上形成的微生物沉积物。研究者们将其描述为主要由很多种细菌和一定量的细胞碎屑组成的柔软的 浓缩物质,其在较短的时间内不刷牙即可形成。牙菌斑不能通过用水漱洗而去除。最近,研究者们己认识到牙菌斑是一种微生物膜。牙菌斑被描述为作为生物膜存在于牙齿表面的多种微生物群。该生物膜包埋在由牙齿表面和微生物有机体形成的细胞外聚合物基质中。人们普遍公认牙菌斑的减少能促进清洁的牙齿,清新的口气和健康的牙龈。然而,牙菌斑生物膜对抗微生物剂非常耐受。
已显示具有明确减少牙菌斑能力的抗微生物剂包括氯己定,西吡氯铵(CPC),三氯生和地莫匹醇。这些都是药用的非天然成分。精油,如麝香草酚,桉叶油素,水杨酸甲酯和薄荷醇及其它在以醇为基础的介质中的精油也被发现能减少牙菌斑。虽然麝香草酚在减少牙菌斑方面最有效,但其具有令人讨厌的味道。通常,这些油受益于醇的存在,以促进其溶解性和对牙菌斑生物膜的渗透性。尽管适用于口腔处理,如漱口剂,但高浓度的醇可以在口腔用组合物,如口香糖,可食用膜和糖果等中留下苦的余味。
可以提供去除牙菌斑,预防或延缓牙菌斑形成的益处,或者具有抗炎作用的活性成分或活性成分的组合物能促进健康的牙龈和清新的口气,所述抗炎作用有助于维持牙龈的健康状态。众所周知,为了提供口腔方面的益处,包括清新口气和杀细菌的特性的目的而在口腔用组合物加入活性剂。这些系统具有提供快速,有效和方便的递送的优点。
发明概述
根据本发明,发明者出乎意料地发现,厚朴提取物与某些表面活性剂组合在抑制导致牙菌斑的细菌的生长方面具有协同作用。厚朴提取物与所选表面活性剂的组合物显示出比单独的厚朴提取物或表面活性剂增强的抗牙菌斑生长的活性。
本发明进一步涉及包含厚朴提取物与表面活性剂的组合物、供杀 细菌和清新口气用的口腔用组合物。更具体的是,本发明涉及包含有效量的厚朴提取物与表面活性剂的口腔递送剂,如牙膏,口香糖,糖果,锭剂,口腔喷雾或可食用膜,通过使用所述牙膏,口香糖,糖果,锭剂,口腔喷雾或可食用膜产品,本发明的组合物有效灭活或杀死口腔细菌并清新口气。表面活性剂被加入到口腔用组合物中,以通过协同作用的方式增加厚朴提取物的效力。
在本发明的一个方面,用于清新消费者口气的口腔用组合物包括口腔递送剂和有效量的抗微生物剂,所述抗微生物剂包括协同比例的厚朴提取物和表面活性剂,其中协同比例为至少约1份厚朴提取物对1份表面活性剂。
适宜的表面活性剂包括但不限于常用表面活性剂,肥皂,润湿剂和乳化剂。表面活性剂的一些例子包括但不限于钾盐,铵盐或钠盐。钠盐包括阴离子表面活性剂,如烷基硫酸盐,包括月桂基硫酸钠,月桂醇聚醚硫酸钠等。其它钠盐包括月桂酰肌氨酸钠,sodium brasslate等。适宜的铵盐包括十二烷基硫酸铵,月桂醇聚醚硫酸铵,月桂酰肌氨酸铵,ammonium brasslate,椰油酰胺基丙基甜菜碱铵盐(ammoniumcocamidopropyl betaine)等。其它适宜的表面活性剂包括乳化剂,所述乳化剂可以是脂肪酸(例如,硬脂酸,棕榈酸,油酸和亚油酸),其盐,单硬脂酸甘油酯,三醋酸甘油酯,卵磷脂,单和三酸甘油酯及乙酰化单酸甘油酯。如下文将要描述的那样,几种表面活性剂自身也显示出一些杀细菌(杀微生物)的特性。
在本发明的另一个方面,口腔用产品是口香糖或任何变种,包括但不限于泡泡糖,丸,胶球或棒。口香糖可以包衣或不包衣,并且可以具有多种风味,形状和大小。用于清新消费者口气的口香糖组合物包括水溶性填充部分,至少一种芳香剂,胶基部分和有效量的抗微生物剂,所述抗微生物剂包括协同比例的厚朴提取物和表面活性剂,其中协同比例为至少约1份厚朴提取物对1份表面活性剂。
在本发明的另一个方面,口腔用产品是糖果组合物,包括但不限于硬糖,咀嚼糖,夹心糖和压制片。用于清新消费者口气的糖果组合物包括糖或糖醇中的至少一种和有效量的抗微生物剂,所述抗微生物剂包括协同比例的厚朴提取物和表面活性剂,其中协同比例为至少约1份厚朴提取物对1份表面活性剂。
在本发明的另一个方面,口腔用产品是可食用膜组合物,其包括有效量的成膜剂和有效量的抗微生物剂,所述抗微生物剂包括协同比例的厚朴提取物和表面活性剂,其中协同比例为至少约1份厚朴提取物对1份表面活性剂。
在本发明的其它方面,清洁口腔的方法包括将口腔用组合物施用于口腔,其中所述口腔用组合物包括有效量的抗微生物剂,其中所述抗微生物剂包括协同比例的厚朴提取物和表面活性剂,其中协同比例为至少约1份厚朴提取物对1份表面活性剂。
发明详述
现已知用口香糖,糖果和薄膜作为介质向口腔递送组分,提供口腔方面的益处,如清新口气和杀细菌特性。这些系统具有为消费者提供方便且价廉的用于在整个一天中保持口腔健康和口气清新的方法的优点。
本发明加入厚朴提取物作为清新口气和口腔杀细菌益处的活性组分。已知厚朴提取物具有杀细菌和抗真菌特性。厚朴酚和和厚朴酚是厚朴提取物中具有抗微生物活性的两种组分。
本发明中所用厚朴提取物可以获自O′Laughlin Industries Co.,LTD,Guang Zhou Masson Pharmaceutical Co.或Honsea SunshineBioscience and Technology Co。厚朴提取物以粉末的形式获得。在制备 口腔用产品之前,将厚朴提取物用香料溶解,并可以加热溶解。
尽管在溶液中杀死细菌相对容易,但牙菌斑生物膜是为细菌和细菌间的协同作用提供对环境威胁的防护的复杂环境(A.Sharma,S.Inagaki,W.Sigurdson,H.K.Kuramitsu,2005,Synergy betweenTannerella forsythia and Fusobacterium nucleatum in biofilm formation,Oral Microbiology and Immunology,20:39-42)。因此,与简单的杀微生物试验相比,显示抗微生物剂对已形成的牙菌斑的真实效力要困难得多。抗微生物剂向生物膜内的扩散是有限的,并且生物膜主体内的细菌受到细胞外物质,如葡聚糖和右旋糖酐多糖的保护而免于暴露在抗微生物剂中。因此,可以说预防牙菌斑的形成比去除已形成的牙菌斑更容易。
根据本发明,厚朴提取物的抗微生物作用通过厚朴提取物与表面活性剂的组合物而得到增强。尽管不希望本发明受到任何特定理论的限制,但我们认为,表面活性剂与有效量厚朴提取物的组合物可以提供这样的口腔用组合物,其促进牙菌斑中和口腔的其它区域,如舌头上的生物膜的减少。我们认为,厚朴提取物与适宜表面活性剂的组合物可以预防细菌向获得膜的粘附。这样的口腔用组合物可以延缓或预防牙菌斑的堆积。此外,本发明的口腔用组合物与酶,其它表面活性剂,磨料或其组合物组合可以有效去除已有牙菌斑。
优选表面活性剂是增加厚朴提取物的溶解度,并且可以用作食品添加剂的表面活性剂。适宜的表面活性剂包括但不限于常用表面活性剂,肥皂,润湿剂和乳化剂。表面活性剂的一些例子包括但不限于钾盐,铵盐或钠盐。钠盐包括阴离子表面活性剂,如烷基硫酸盐,包括月桂基硫酸钠,月桂醇聚醚硫酸钠等。其它钠盐包括月桂酰肌氨酸钠,sodium brasslate等。适宜的铵盐包括十二烷基硫酸铵,月桂醇聚醚硫酸铵,月桂酰肌氨酸铵,ammonium brasslate,椰油酰胺基丙基甜菜碱铵盐(ammonium cocamidopropyl betaine)等。其它适宜的表面活性剂 包括乳化剂,所述乳化剂可以是脂肪酸(例如,硬脂酸,棕榈酸,油酸和亚油酸),其盐,单硬脂酸甘油酯,三醋酸甘油酯,卵磷脂,单和三酸甘油酯及乙酰化单酸甘油酯。如下文将要描述的那样,几种表面活性剂自身也显示出一些杀细菌(杀微生物)的特性。
口腔用组合物还可以包括其它清新口气或维护口腔健康的成分,其可以是抗微生物成分。此外,所述其它清新口气或维护口腔健康的成分还可以包括食品上可接受的锌或铜盐,清凉剂,焦磷酸盐或多磷酸盐等。
本发明还包括降低消费者口腔中细菌的数量或活性的处理方法,所述方法包括提供口腔用组合物和使需要所述处理的人使用所述口腔用组合物的步骤,通过所述处理,该人口腔中的细菌被所述处理减少或灭活,所述口腔用组合物包括足以杀死或灭活口腔细菌的量的厚朴提取物与表面活性剂的组合物。
在一种形式中,口腔用组合物用口腔递送剂配制,以向口腔递送浓度为至少约0.001%至约2.0%的厚朴提取物。在另一种形式中,口腔用组合物用口腔递送剂配制,以向口腔递送浓度为至少约0.01%的厚朴提取物。为了增强口腔用组合物在向口腔递送有效量中的效力,向口腔用组合物中加入了一种或多种表面活性剂。
根据本发明的一个实施方案,一种或多种表面活性剂以约0.001%至约2.0%的浓度范围存在于口腔用组合物中。在口腔用组合物中,厚朴提取物与表面活性剂以提供增强的杀微生物效力的协同比例组合。协同比例的范围为从约1份厚朴提取物对1份表面活性剂至约4份厚朴提取物对1份表面活性剂。一种尤其有效的表面活性剂是月桂基硫酸钠,尤其有效的协同组合物是约2份厚朴提取物对1份月桂基硫酸钠。
鉴于厚朴提取物是疏水化合物,有几种口腔递送剂可以用来增强厚朴提取物从口腔用组合物中的释放。在口香糖产品中,胶基是疏水的,其也可以抑制厚朴提取物的释放。在本发明的糖果组合物的多种实施方案中,为了促进厚朴提取物向口腔内的释放,将厚朴提取物与表面活性剂组合,并且可以将其包囊,喷雾干燥或制成包衣,或其组合。
为了评价厚朴提取物的效力,用与口臭相关的三种龈下菌斑细菌进行体外试验。最小抑制浓度(MIC)的研究方案如下。以氯己定为阳性对照,无菌水为阴性对照。薄荷醇和吐温80用作厚朴提取物的溶剂。吐温80是聚山梨醇酯80的普通名。本研究使用96孔微量滴定板。每孔各含有5×105菌落形成单位/ml的细菌,连续稀释剂和细菌生长培养基。所有细菌培养物均在37℃静置孵育。48h后,用分光光度计在660nm处测量,对细菌生长进行评价。各供试细菌的MIC的定义为供试化合物限制浊度至660nm处的吸光度小于0.05时的最小浓度。
如上文MIC研究所述,用96孔微量滴定板连续稀释法测定最小杀菌浓度(MBC)。对显示无可见生长的孔中的培养物进行连续稀释,并将10μl培养物接种于血琼脂板上,一式三份。将血琼脂板在37℃孵育48小时后,对活菌落计数。对于各供试细菌,测定初始接种物的菌落形成单位/ml(CFU/ml)的量。MBC的定义为供试化合物杀死初始接种物中存在的至少99.9%的细胞时的最低浓度。
为获得厚朴提取物(MBE)的MIC和MBC而进行的研究结果如下。对于变形链球菌(Streptococcus mutans),90%厚朴提取物的MIC为15.62μg/ml。对于牙龈卟啉单胞菌(Porphyromonas gingivalis),90%厚朴提取物的MIC为3.91μg/ml,65%厚朴提取物的MIC为7.82μg/ml。对于具核梭杆菌(Fusobacterium nucleatum),90%厚朴提取物的MIC为3.91μg/ml,MBC为7.82μg/ml。对于同一生物体,65%厚朴提取物的MIC和MBC为7.82μg/ml。氯己定是阳性对照,其对所有三种细 菌的MIC和MBC都是1.25μg/ml。由水和10%甲醇及3.8%吐温80组成的溶剂对本研究中的三种细菌均未见明显生长抑制作用。
同样已知的是,厚朴提取物能有效对抗伴放线放线杆菌(Actinobacillus actinomyecetemcomitans),中间普雷沃菌(Prevotellaintermedia),藤黄微球菌(Micrococcus luteus)和枯草芽孢杆菌(Bacillussubtilis),殊异韦荣菌(Veillonella disper),牙龈二氧化碳嗜纤维菌(Capnocytophaga gingivalis),牙周微生物及牙龈成纤维细胞。
除了上文所述结果外,还将厚朴提取物与不同草本和天然成分对生物膜的形成和去除的影响进行了比较。比较试验用绿茶提取物,乌龙茶提取物,甘草精和厚朴提取物(Masson Pharma厚朴提取物MBE90)进行。比较试验包括测定在水,乙醇,水-乙醇混合物和其它溶剂(例如,吐温水溶液)中的溶解度,对变形链球菌(S.mutans)生长的MIC,对96孔板中变形链球菌生物膜形成的MIC以及对变形链球菌生物膜脱落的影响。
绿茶提取物溶于水;所有其它物质可溶于2∶1的水-乙醇混合物。厚朴提取物还溶于0.01μl 50%的吐温80水溶液。
为了进一步评价对变形链球菌生物膜形成的影响,使用了96孔微量滴定板。每孔各含有变形链球菌(5×106CFU/ml),用供试化合物和生长培养基(含0.5%蔗糖的BHI)连续稀释。对照包括已接种的生长培养基,但不含供试化合物。所有平板在37℃,好气条件下孵育,48h后用微量滴定板阅读器采用分光光度法(660nm)对生长进行评价。然后,从各孔中吸出含有未贴壁细胞的上清液,贴壁的生物膜团块用200μl 1N NaOH溶解,用微量滴定板阅读器在660nm处测量光密度。以氯己定(40μg/ml)作为阳性对照。
为了进一步评价对变形链球菌生物膜脱落的影响,使用了无菌96 孔微量滴定板,该板各孔接种有变形链球菌(5×106CFU/ml),生长培养基(含0.5%蔗糖的脑心浸液肉汤(BHI)),并在37℃,好气条件下孵育,以形成生物膜。48小时后,吸出未贴壁的上清液,并连续稀释。向预形成的生物膜中加入供试化合物,在37℃,好气条件下孵育。对照包括溶剂,但不含供试化合物。30min后,从孔中吸出上清液,将处理后剩下的生物膜溶解在200μlIN NaOH中,用微量滴定板阅读器在660nm处定量。用氯己定作阳性对照。如果由于供试化合物的作用而发生了生物膜的脱落,则分光光度计测量的吸光度或光密度(OD)与未处理对照相比应显示降低。
比较试验的结果见下表1。各化合物的实验结果以μg/ml为单位显示。表1和下面的各表中,厚朴提取物用“MBE”表示,氯己定阳性对照用“CHX”表示。
表1
表1所示数据表明,供试化合物中没有任何化合物比氯己定在去除已形成的生物膜方面更有效。绿茶提取物,甘草提取物和厚朴提取物可通过抑制细菌生长而抑制变形链球菌生物膜,因为其对生长和生物膜形成的MIC都相同。厚朴提取物在抑制生长和生物膜形成方面最有效,并且处于氯己定阳性对照的数量级内。
尽管比较显示厚朴提取物对生物膜形成和对生长的MIC的影响是有用的,但前述试验程序不能有效模拟口腔用组合物,如口香糖向形 成中的牙菌斑生物膜的体内暴露。在体内情况下,活性剂可以设定的频率在牙菌斑暴露指定的时间(例如,5min,一天3次)。因此,进行了一系列对比实验,以模拟潜在活性成分的体内使用情况。为完成该试验,制备了下表2和3中所列缓冲液组合物。
表2
表3
使用了利用来自新收集的刺激性全唾液的细菌的混合培养系统。 用唾液细胞团接种经唾液涂敷的羟基磷灰石(S-HA)盘。将该盘置于24孔细胞培养板中,孵育3天。生物膜在第2和第3天暴露于活性剂(开始于第18小时),并在第4天定量。细菌数通过用分光光度计在660nm处测定吸光度或光密度(OD)而确定。该实验的5个阶段为:菌膜的形成;细菌的附着;生物膜的生长;暴露于活性剂;和细菌计数。
为了形成菌膜,将HA盘在去离子水中超声洗涤,并风干,然后高压灭菌。在室温下将该盘与1ml 50%无菌唾液(1份无菌全唾液:1份唾液缓冲液,制备后过滤除菌)一起置于24孔板中2小时,同时缓慢搅拌。吸出唾液,然后将盘转移至新的孔中进行细菌附着。
通过以下两种方法中的一种将盘接种唾液细菌:(1)在37℃与具有标准OD的悬浮在50%唾液中的唾液细菌一起孵育2h;附着阶段过后,将盘转移至补加唾液生长培养基,或(2)直接加入细菌和培养基,并孵育。
为了形成生物膜,除去细菌悬浮液,将盘转移至新的孔中。加入1ml补加唾液培养基,将板置于孵育器中孵育过夜,至该实验的持续时间(一直到72小时)。
制备1%厚朴提取物的60%乙醇储备液。用磷酸盐缓冲盐水(PBS)溶液制备浓度范围为125,250,500和1000μg/ml(ppm)的厚朴提取物样品,阴性对照是PBS,阳性对照是浓度为0.12%的CHX。PBS对照溶液具有下表4中所示组合物。
将1ml活性成分和对照置于新的孔中,将盘置于这些孔中5min。氯己定对照的暴露时间为1min,一天2次,以模拟标准漱口程序。活性成分的暴露在上午8:00,12:00和下午4:00进行。在定时暴露后,除去溶液,盘用PBS洗涤2次,然后转移至新鲜培养基中。对于一些实验,这一天所使用的培养基是胰胨豆胨培养液(TSB),各孔中加入了50μl 40%的无菌蔗糖溶液(以得到2%蔗糖溶液)。培养基在中午的暴露后未更换。
过夜孵育(第2天)后,将盘暴露于对照和活性剂中。在第3天将生物膜再次暴露于试验组和对照中。在第4天将盘从培养基中取出,测定培养基的pH,以获得代谢活性的指征,将盘置于含有2.5ml PBS的试管中,涡旋20s,然后再置于超声波浴中20s。将悬浮液转移到样品池中,通过OD测量法在600nm处测定细菌细胞密度。
pH测量的结果见下表5,OD相对于PBS对照的百分减少率见下表6。
表5
表6
上表5和6中所示结果说明厚朴提取物对生物膜代谢活性(通过培养基的pH确定)和生物膜形成(OD)具有明确的抑制作用和剂量效应关系。氯己定对菌斑代谢和细胞数量具有强烈的抑制作用。厚朴提取物不如氯己定有效,但氯己定的浓度稍高于厚朴提取物。
为了评价厚朴提取物与表面活性剂月桂基硫酸钠的组合物的作用,用上文所述程序制备了5种活性成分的溶液。制备了浓度稍微降低至0.1%(1000ppm)的氯己定对照溶液。同样还制备了浓度为500ppm的MBE溶液。向2种厚朴提取物的溶液中加入月桂基硫酸钠,得到SLS浓度为0.05%和0.1%的厚朴提取物溶液。用此5种溶液重复上文所述厚朴提取物的试验。
pH测试结果见下表7,其中月桂基硫酸钠用“SLS”表示。
表7
光密度(OD)百分减少率的试验结果见下表8。注意:该表最后一行的数据取自不同的实验。
表8
上表7和8中所列结果显示,氯己定对照的pH最高,并且该对照还具有最低的OD。根据pH数据(代谢活性的指征),单独的500ppm厚朴提取物显示出比月桂基硫酸钠或厚朴提取物/月桂基硫酸钠混合物更强的代谢抑制作用。然而,OD吸光度数据(细菌数)却表明,组合了厚朴提取物和月桂基硫酸钠的供试溶液在减少生物膜方面具有协同效应。尤其是,结果显示,就菌斑量而言,虽然厚朴提取物对菌斑代 谢活性的抑制更强,但1000ppm月桂基硫酸钠和500ppm厚朴提取物具有相似的作用。与单独的500ppm厚朴提取物相比,含有500ppm月桂基硫酸钠的厚朴提取物减少了菌斑的生长。此外,1000ppm月桂基硫酸钠与500ppm厚朴提取物组合不如500ppm月桂基硫酸钠与500ppm厚朴提取物组合有效。最有效的组合是1000ppm厚朴提取物与500ppm月桂基硫酸钠的组合。
尽管不希望受到任何关于本发明的作用机制的特定理论的限制,但厚朴提取物/月桂基硫酸钠混合物减少细胞团,同时却增强代谢活性的相互矛盾的作用的原因可能与月桂基硫酸钠使厚朴提取物更快速渗透入生物膜的作用有关,在生物膜内,厚朴提取物具有直接杀死微生物和/或抑制生长的作用,但厚朴提取物还可以较容易地冲洗掉,因此,其直接性和延长的代谢作用被最小化。
为评价两种或两种以上的杀微生物活性剂组合时的杀微生物效力和协同作用,进行了试验以测定MBE与表面活性剂的比例。将杀微生物活性剂和/或表面活性剂溶解在乙醇或无菌水中,得到初始浓度为0.1%-1%的溶液。将该溶液用营养肉汤稀释,得到初始浓度0.05%-0.5%,然后连续2倍稀释,使各稀释液保持营养素水平恒定的条件下,后一稀释液中所含有的化合物的浓度是前一稀释液的50%。将这些稀释液接种以代表性的口腔微生物或孵育的唾液,并在37℃孵育24h。对于各表面活性剂,将无混浊的最低稀释液记为MIC。通过将10μl来自无混浊管的液体转移至新鲜生长培养基中,并孵育48小时,测定MBC。对于各表面活性剂,未显示生长的最低稀释液被认为是MBC。
下表9显示了各种表面活性剂和乳化剂对孵育的唾液的MIC。
表9
*用作阳性对照
结果显示桂硫酸钠,椰油酰胺基丙基甜菜碱是良好的杀微生物表面活性剂,而sodium brasslate则显示出中等的杀微生物效力。硬脂酰乳酸钠,聚山梨酯20(通常称作吐温20),蔗糖硬脂酸酯和蔗糖二硬脂酸酯的杀微生物活性较弱或无杀微生物活性。
为评价活性成分与表面活性剂组合的协同作用,根据下述方程式(1)计算分级抑制指数(FIC):
(1)FIC=[MIC与B组合的A/MIC单独的A+MIC与A组合的B/MIC单独的B]
其中小于1.0的FIC值表示协同作用,1.0-2.0的FIC值表示累加作用,大于2.0的FIC值表示拮抗作用。
下表10显示了组合物厚朴提取物/月桂基硫酸钠和厚朴提取物/吐温-20对变形链球菌的MIC值:
表10
结果表明,当厚朴提取物与月桂基硫酸钠以约1/4至约4/1的比例(MBE/SLS)组合时显示协同作用(FIC<1)。然而,当厚朴提取物与吐温-20组合时显示出了拮抗作用(FIC>2)。
尤其是,结果显示了某些比例的厚朴提取物和月桂基硫酸钠具有协同作用。因此,本发明包括含有协同比例的厚朴提取物和表面活性剂的口腔用组合物。根据前述实验结果,口腔用组合物中厚朴提取物与表面活性剂组合将产生协同抗微生物作用。具有浓度范围约25ppm至约500ppm的表面活性剂与厚朴提取物的组合物的口腔用组合物在抑制导致牙菌斑的生物膜形成方面显示出协同特性。此外,重量比为至少约1份厚朴提取物对1份表面活性剂的口腔用组合物将产生协同抗微生物作用。另外,厚朴提取物与表面活性剂的协同比例的范围可以为从约1份厚朴提取物对1份表面活性剂至约4份厚朴提取物对1份表面活性剂。最优选的是,协同比例为约2份厚朴提取物对1份表面活性剂。因此,本发明包括宽范围的包含厚朴提取物与表面活性剂的协同组合物的口腔用组合物。
实施例
下文所列实施例不希望排除制剂的其它变化,并且本发明不限于这些制剂。
口香糖制剂
在本发明的一方面,有效抗微生物量的厚朴提取物与表面活性剂,如上文所述表面活性剂的组合物存在于口香糖制剂中。在本发明的另一方面,厚朴提取物以按重量计占口香糖产品的高达5%的量存在。在本发明的另一方面,厚朴提取物的量是口香糖产品重量的1%。在另一方面,厚朴提取物以按重量计占口香糖产品的0.01%的量存在。鉴于上文体外研究中所述厚朴提取物的效力,低至以重量计占口香糖产品的0.005%的水平应该即具有有效杀细菌的特性。因此,厚朴提取物的有效量可以在以重量计占组合物的约0.005%至约5%的范围内变动。口香糖制剂中月桂基硫酸钠的绝对量可以在约4mg至约10mg的范围内变动。
一般而言,口香糖组合物通常包括水溶性填充部分,水不溶性可咀嚼胶基部分和通常为水溶性的芳香剂。水溶性填充部分和部分芳香剂在咀嚼一段时间后消失。胶基部分在整个咀嚼过程中一直保留在口腔内。
不溶性胶基通常包括高弹体,树脂,脂肪和油,软化剂和无机填充剂。胶基可以包括或不包括蜡。不溶性胶基以重量计可以构成口香糖的约5%至约95%,更常见的是胶基占口香糖的10%至约50%,在一些优选实施方案中,胶基以重量计占口香糖的约25%至约35%。
在特定实施方案中,本发明的口香糖胶基含有以重量计约20%至约60%的合成高弹体,以重量计高至约30%的天然高弹体,以重量计约5%至约55%的高弹体增塑剂,以重量计约4%至约35%的填充剂,以重量计约5%至约35%的软化剂和任选的少量(以重量计约1%或更 少)各种成分,如着色剂,抗氧化剂等。
合成高弹体可以包括但不限于GPC重均分子量为约10,000至约95,000的聚异丁烯,异丁烯-异戊二烯共聚物(丁基高弹体),苯乙烯-丁二烯比例为约1∶3至约3∶1的苯乙烯共聚物,GPC重均分子量为约2,000至约90,000的聚乙酸乙烯酯,聚异戊二烯,聚乙烯,月桂酸乙烯酯的含量以重量计占共聚物的约5%至约50%的乙酸乙烯酯月桂酸乙烯酯共聚物及其组合物。
对于聚异丁烯,优选范围是50,000-80,000的GPC重均分子量;对于苯乙烯,优选范围是1∶1-1∶3结合的苯乙烯;对于聚乙酸乙烯酯,优选范围是10,000-65,000的GPC重均分子量,更高分子量的聚乙酸乙烯酯通常用于泡泡糖胶基;对于乙酸乙烯酯月桂酸乙烯酯,优选范围是月桂酸乙烯酯的含量为10。
天然高弹体可以包括天然橡胶,如烟胶或液态胶乳和银菊胶,及天然树胶,如节路顿胶,lechi caspi,perillo,sorva,二齿铁线子胶,巧克力铁线子,nispero,rosindinha,糖胶树胶,古塔胶,和其组合物。如下文所述,优选合成高弹体和天然高弹体的浓度根据该胶基被使用的口香糖是粘性的还是常规的,是泡泡糖还是普通口香糖而变化。优选天然高弹体包括节路顿胶,糖胶树胶,sorva和二齿铁线子胶。
高弹体增塑剂可以包括但不限于天然松香酯,如甘油酯或部分氢化松香,聚合松香的甘油酯,部分二聚松香的甘油酯,松香的甘油酯,部分氢化松香的季戊四醇酯,松香的甲酯和部分氢化甲酯,松香的季戊四醇酯;合成物,如衍生自α-萜烯,β-萜烯和/或前述成分的任何适宜的组合物的萜烯树脂。优选高弹体增塑剂也将根据具体应用和所用高弹体的类型的不同而变化。
填充剂/质地成构剂(texturizer)可以包括碳酸镁和碳酸钙,重质 碳酸钙,硅酸盐类,如硅酸镁和硅酸铝,粘土,矾土,滑石粉,二氧化钛,单,二和三磷酸盐,纤维素聚合物,如木材,及其组合物。
软化剂/乳化剂可以包括动物脂,氢化动物脂,氢化和部分氢化植物油,可可脂,单硬脂酸甘油酯,三醋酸甘油酯,卵磷脂,单和三酸甘油酯,乙酰化单酸甘油酯,脂肪酸(例如,硬脂酸,棕榈酸,油酸和亚油酸)及其组合物。
着色剂和增白剂可以包括FD&C染料和色淀,果实和植物提取物,二氧化钛及其组合物。
胶基可以包括或不包括蜡。无蜡胶基的例子公开于美国专利5,286,500中,其引入本文作为参考。
除了水不溶性胶基部分外,典型的口香糖组合物还包括水溶性填充部分和一种或多种芳香剂。水溶性部分可以包括填充型甜味剂,高强度甜味剂,芳香剂,软化剂,乳化剂,色料,酸化剂,填充剂,抗氧化剂和其它提供预期属性的组分。
为了优化口香糖的可咀嚼性和口感,向口香糖中加入了软化剂。也被称作增塑剂和塑化剂的软化剂通常构成口香糖重量的约0.5%至约15%。软化剂可以包括甘油,卵磷脂和其组合物。甜味剂水溶液,如含有山梨醇,氢化淀粉水解物,玉米糖浆和其组合物的水溶液也可以在口香糖中用作软化剂和粘合剂。
填充型甜味剂或填充剂包括糖和非糖组分。填充型甜味剂通常构成口香糖重量的约5%至约95%,更通常的是构成口香糖重量的约20%至约80%,更通常的是构成口香糖重量的约30%至约60%。糖类甜味剂一般包括口香糖领域公知的糖类组分,包括但不限于单独或组合的蔗糖,右旋糖,麦芽糖,糊精,干燥转化糖,果糖,左旋糖,半乳糖, 玉米糖浆固体等。非糖甜味剂包括但不限于单独或组合的糖醇,如山梨醇,甘露醇,木糖醇,氢化淀粉水解物,麦芽糖醇等。
高强度人造甜味剂可以单独或与上述甜味剂组合使用。优选甜味剂包括但不限于单独或组合的三氯蔗糖,阿司帕坦,NAPM衍生物,如纽甜,乙酰舒泛的盐,altitame,糖精及其盐,环拉酸及其盐,甘草酸盐(glycyrrhizinate),双氢查耳酮,索马甜(thaumatin),莫尼糖蛋白(monellin)等。为了提供更持久的甜味和香味,理想的是包囊或以其它方式控制至少部分人造甜味剂的释放。可以用如湿法制粒,蜡制粒,喷雾干燥,喷雾冷冻,流化床包衣,凝聚和纤维延长这样的技术来获得预期的释放特征。
在口香糖中可以使用糖和/或非糖甜味剂的组合物。此外,软化剂也可以提供额外的甜味,如用糖或糖醇水溶液。
如果希望得到低卡路里的口香糖,可以使用低卡路里的填充剂。低卡路里的填充剂的例子包括:聚右旋糖;raftilose;raftilin;低聚果糖(NutraFlora);低聚帕拉金糖;瓜尔胶水解物(Sun Fiber);或难消化糊精(Fibersol)。然而,其它低卡路里的填充剂也可以使用。
如果需要,还可以使用各种芳香剂。香料的用量以重量计可以为口香糖的约0.1%至约15%,优选约0.2%至约5%。芳香剂可以包括精油,合成香料或其混合物,包括但不限于源自植物和果实的油,如柠檬油,水果香精(fruit essences),薄荷油,留兰香油,其它薄荷油,丁香油,冬青油,茴香等。人造芳香剂和组分也可以使用。天然和人造芳香剂可以任何感觉上可接受的方式组合。芳香剂可以包括清凉剂,以增强产品的香味和被感知的口气的清新。清凉剂包括薄荷醇,乙基对薄荷烷羧酰胺,N,2,3-三甲基-2-异丙基-丁酰胺,戊二酸薄荷酯(香料提取物制造协会(FEMA 4006)),琥珀酸薄荷酯,薄荷醇PG碳酸酯,薄荷醇EG碳酸酯,乳酸薄荷酯,薄荷酮甘油缩酮,薄荷甘油醚, N-叔丁基-对-薄荷烷-3-羧酰胺,对-薄荷烷-3-羧酸甘油酯,甲基-2-异丙基-二环(2.2.1)庚烷-2-羧酰胺,薄荷醇甲醚及其组合物。
除了本发明的厚朴提取物和表面活性剂外,为了不同目的也可以加入其它活性成分或药物。如果口香糖中的药物或活性剂是水溶性的,则口香糖优选包括导致唾液中具有预期浓度的药物的胶基/乳化剂系统(更亲水的平衡)。如果药物或活性剂是水不溶性的,则口香糖优选包括导致唾液中具有预期浓度的药物的胶基/乳化剂系统(更亲脂的平衡)。
在包括活性剂或成分的口香糖的生产过程中,活性剂或药物优选在混合的早期加入。所使用的活性成分的量越小,就越有必要将该特定成分预混合,以确保在整批口香糖中的均匀分布。不管是否采用预混合,活性剂或药物都应该在混合的前5min内加入。为了快速释放,活性剂可以在工艺的晚期加入。
本发明的口香糖可以任选地包括其它清新口气,抗微生物或健康口腔的成分,如食品上可接受的选自葡糖酸的锌和铜盐,乳酸的锌和铜盐,乙酸的锌和铜盐,柠檬酸的锌和铜盐,叶绿素铜及其组合物的金属盐。此外,还可以向口香糖组合物中加入抗微生物精油和香料组分,如薄荷,水杨酸甲酯,麝香草酚,桉叶油素,肉桂醛,多磷酸盐,焦磷酸盐及其组合物。健齿成分,如氟化盐,磷酸盐,蛋白水解酶,脂质,抗微生物剂,钙,电解质,蛋白添加剂,磨牙粉及其组合物也可以加入到口香糖组合物中。
一般而言,口香糖通过向本领域已知的市场上可以买到的混合器中依次加入各种口香糖成分而制得。各成分充分混合后,将口香糖团块从混合器中取出,定型成预期的形式,如滚压成片和切割成条状物,挤压成大块或铸成小丸,然后包衣或浇洒。
通常,首先将胶基熔化,并将其加入到正在运行的混合器中混合各成分。胶基也可以在混合器中自己熔化。此时也可以加入色料或乳化剂。软化剂,如甘油此时也可以与糖浆和部分填充剂一起加入。将其它部分的填充剂加入混合器中。芳香剂通常与最后一部分的填充剂一起加入。其它任选成分以本领域技术人员公知的典型方式加入到批样中。
整个混合程序通常花费5-15min,但有时可能需要更长的混合时间。本领域技术人员将认识到可以采用上文所述程序的多种变体。
按照惯例,口香糖胶基和口香糖产品用独立的混合器,不同的混合技术并且通常在不同的工厂生产。造成这样的一个原因是生产胶基和由胶基及其它成分,如甜味剂和香料生产口香糖的最佳条件有很大不同,以致于合并这两项工作是不现实的。一方面,口香糖胶基的生产涉及难以混合的成分,如高弹体,填料,高弹体增塑剂,胶基软化剂/乳化剂和有时含有的蜡的分散性(通常高剪切力)混合,通常需要较长的混合时间。另一方面,口香糖产品的生产涉及采用(通常低剪切力)分布性混合将胶基与更微妙的成分,如产品软化剂,填充型甜味剂,高强度甜味剂和芳香剂混合,混合时间较短。
下表11列出了厚朴提取物的口香糖制剂的实施例。实施例1是现有技术口香糖制剂的对比实施例。
表11
根据本发明,实施例2-5中的制剂均补充有上文所述表面活性剂。在一个例示性实施方案中,实施例2-5各包括约0.001%至约2%的上文所述表面活性剂。在另一个例示性实施方案中,实施例2-5各包括约0.001%至约2.0%的上文所述表面活性剂。在另一个例示性实施方案中,实施例2-5各包括比例为约1/4至约4/1的月桂基硫酸钠和厚朴提取物。
可食用膜制剂
在本发明的一方面,有效抗微生物量的厚朴提取物与表面活性剂,如上文所述表面活性剂的组合物存在于可食用膜制剂中。在本发明的另一方面,厚朴提取物以占可食用膜制剂重量的高达10%的量存在。在本发明的另一方面,厚朴提取物的量是可食用膜产品重量的约8%。在另一方面,厚朴提取物以占可食用膜产品重量的约5%的量存在。鉴于上文体外研究中所述厚朴提取物的效力,以重量计占可食用膜产品的约1%的厚朴提取物也具有有效杀细菌的特性。因此,厚朴提取物的 有效量可以在以重量计占组合物的约1%至约10%的范围内变动。可食用膜制剂中月桂基硫酸钠的绝对量可以在约4mg至约10mg的范围内变动。
本发明提供了用于口腔粘膜附着的可食用膜制剂及使用和制备其的方法。尤其是,本发明的可食用膜包括至少3种类型的除普鲁兰多糖以外的成膜剂。
本发明的申请者独特地发现,至少3种类型的成膜剂,如麦芽糊精,填料(例如,微晶纤维素(MCC))和水胶体(例如,海藻酸钠)的混合物的使用可以有效制备无与伦比的可食用膜。可食用膜由容易获得的成分构成,与由普鲁兰多糖构成的可食用膜相比可以较低的成本制得,并显示出相似的特性。就这一点而言,可食用膜可以提供生理学上可接受的适合附着于口腔表面并在那里迅速溶解的膜。
本发明的可食用膜可以用来递送或释放口腔护理剂。这些剂包括治疗例如口臭,牙菌斑,龈炎,口干燥症,口干,相似口腔环境或其组合的抗微生物剂和唾液刺激剂。此外,口腔护理用可食用膜可以作为口气清新剂有效对抗口臭。
本发明的可食用膜的清洁口腔和清新口气的作用可以通过将口腔护理剂截留在口腔内以提供延长的效力而实现。就这一点而言,高度可溶性可食用膜可以起介质的作用,通过它,药学活性口腔用剂可以经口腔粘膜给药。
此外,可食用膜还可以包括多种其它适宜成分,如软化剂,着色剂,芳香剂,乳化剂,表面活性剂,增稠剂,粘合剂,甜味剂,香精,其它类似成分或其组合物。
在实施方案中,可食用膜优选包括至少3种类型成膜剂,如麦芽 糊精,填充剂和水胶体的混合物。应该了解的是,本发明的可食用膜可以由一种或多种不同化合物与所述至少3种类型的成膜剂各自组合构成。
在实施方案中,麦芽糊精组分以干量计构成可食用膜的约5%至约60%,优选约20%至约40%。麦芽糊精组分可以以任何适宜的方法进行加工。
水胶体可以为可食用膜提供厚度,并降低其脆性。水胶体可以包括任何适宜类型,数量和数目的水胶体。在实施方案中,水胶体以干重计可以构成可食用膜的约10%至约50%,优选约20%至约30%。水胶体可以得自,例如,天然海藻,天然籽胶,天然植物渗出物,天然纤维提取物,生物合成胶,明胶,生物合成法处理的淀粉或纤维素材料,藻酸盐,藻酸钠,藻酸钙,卡拉胶,瓜尔胶,刺槐豆胶,他拉胶,阿拉伯胶,印度胶,琼脂,黄原胶,果胶,其它类似水胶体源材料或其组合物。
任何适宜的食品级填充剂都可以添加到可食用膜中。这可以减少任何粘性质感,并为可食用膜提供结果,从而使其更加可口。在实施方案中,以干重计,填料可以构成可食用膜的约5%至约30%,优选约15%至约25%。填料可以包括,例如,微晶纤维素,纤维素聚合物,如木材,碳酸镁和碳酸钙,重质碳酸钙,硅酸盐,如硅酸镁和硅酸铝,粘土,滑石粉,二氧化钛,磷酸二氢钙,磷酸二钙,磷酸三钙,其它类似填充剂或其组合物。
我们认为,至少3种非普鲁兰多糖成膜剂,例如,麦芽糊精,水胶体和填充剂的独特混合物可以提供无与伦比的可食用膜组合物,所述组合物显示出许多由更昂贵的以普鲁兰多糖为基础的可食用膜所表现出的相同的预期特性。本发明的申请者发现,本发明的无普鲁兰多糖可食用膜制剂可以表现出例如,与现有以普鲁兰多糖为基础的膜类 似的纯净的口感,纯净的香味和生产的容易性。
如先前讨论的那样,可以向本发明的可食用膜中加入多种其它适宜成分。例如,任何适用于清洁口腔,清新口气等的药物都可以加入到可食用膜制剂中。药物可以包括,例如,pH控制剂,如尿素和缓冲液,用于控制牙石或龋的无机组分,如磷酸盐和氟化物,口气清新剂,如葡萄糖酸锌,抗菌斑/抗龈炎剂,如氯己定,CPC和三氯生,唾液刺激剂,包括,例如,食品酸味剂,如柠檬酸,乳酸,马来酸,琥珀酸,抗坏血酸,己二酸,富马酸和酒石酸,药用成分,营养剂,维生素,矿物,其它类似药物或其组合物。
药物可以递送或释放至口腔中用于有效的口腔治疗,如清洁口腔和/或清新口气。就这一点而言,可食用膜的成膜剂可以起到将药物截留在口腔内,从而提供其延长的效力的作用。在这种情况下,我们认为,本发明的无普鲁兰多糖可食用膜组合物比先前获得的膜更能均匀地释放药物至口腔中,用于经开放性伤口或粘膜吸收。此外,我们还相信,本发明的成膜剂的混合物可以将药物截留在口腔内较长的时间,以延长和增强该药物的效力。另外,通过延长药物在口腔内的接触时间,该药物被吸收得更多,从而增加了其生物利用度。
如果使用的成膜剂的水平降低,可以用软化剂来降低所得膜的脆性。也被称作增塑剂和塑化剂的软化剂通常构成可食用膜干重的约20%,优选约2%至约10%。软化剂可以包括增塑剂,包括,例如,山梨醇和其它多元醇,甘油,聚乙二醇,丙二醇,氢化淀粉水解物,玉米糖浆,其它类似材料或其组合物。
本发明的可食用膜制剂还可以包括着色剂或染色剂,其可以以任何适于产生预期颜色的量使用。染色剂可以包括,例如,适用于食品,药品和化妆品的天然食品色素和染料。代表性的着色剂有FD&C染料和色淀。
还可以向可食用膜中加入各种芳香剂。任何适宜量和类型的人造和/或天然芳香剂都可以以任何感觉上可接受的方式使用。例如,香料可以构成可食用膜干重的约0.1%至约20%,优选约10%至15%。芳香剂可以包括,例如,精油,合成香料或混合物,包括但不限于源自植物和果实的油,如柠檬油,水果香精,薄荷油,留兰香油,其它薄荷油,丁香油,冬青油,茴香等,具有杀微生物特性的香味油,如薄荷醇,桉叶油素,麝香草酚,类似芳香剂或其组合物。
香料可以通过乳化作用而得到增强,并在整个产品中均匀分布。任何适宜量和类型的天然和/或合成食品级乳化剂都可以使用。例如,乳化剂可以包括卵磷脂,食品级非离子乳化剂,如脂肪酸(C10-C18),单和二酰基甘油酯,牛胆汁提取物,聚甘油酯,聚乙二醇,脱水山梨糖醇酯,丙二醇,脱水山梨醇单棕榈酸酯,脱水山梨醇单硬脂酸酯,脱水山梨醇三硬脂酸酯,酶改性卵磷脂,羟基化卵磷脂,其它类似乳化剂或其组合物。
香料可以通过任何适宜的乳化工艺,如机械处理,强力搅拌,在湍流,如匀浆,超声,胶体研磨中发生的强烈压力脉动等而乳化。
本发明提供了生产可食用膜制剂的方法。一般而言,可食用膜制剂通过形成包含至少3种类型的成膜剂,如麦芽糊精,水胶体和填料的基础溶液,并将该基础溶液加工成可食用膜而制得。通常,基础溶液通过向水中加入干燥成分的初始混合物,搅拌而制得。
基础溶液中可以加入其它成分,如香料/乳化剂掺合物,甜味剂,软化剂,色素等或其组合物。在实施方案中,不断搅拌该溶液,并在约40℃至约60℃的温度范围内加热。然后溶液可以以任何适宜的方式干燥,从而形成可食用膜。
应该了解的是,任何适宜类型,数量和排列的工艺程序或步骤(即,混合,加热,干燥,冷却,成分的加入),工艺参数(即,温度,压力,pH,加工时间)等都可以采用。
作为例子而非限制,下表12和13中的下列实施例列举了本发明的可食用膜制剂的多种实施方案。
表12
根据本发明,实施例6-10中的制剂都补充有上文所述表面活性剂。
表13
根据本发明,实施例6-15中的制剂均补充有上文所述表面活性剂。在一个例示性实施方案中,实施例6-15各包含约0.01%至约2%的上文所述表面活性剂。在另一个例示性实施方案中,实施例6-15各包含约0.001%至约2.0%的上文所述表面活性剂。在另一个例示性实施方案中,实施例6-15各包含比例为约1/4至约4/1的月桂基硫酸钠和厚朴提取物。
糖果制剂
在本发明的一方面,有效抗微生物量的厚朴提取物与表面活性剂,如上文所述表面活性剂组合,存在于糖果制剂中。在本发明的另一方面,厚朴提取物以按重量计占糖果产品的高达3%的量存在。在本发明 的另一方面,厚朴提取物的量是糖果产品重量的1%。在另一方面,厚朴提取物以按重量计占糖果产品的0.01%的量存在。鉴于上文体外研究中所述厚朴提取物的效力,以重量计占糖果产品的0.005%的厚朴提取物也具有有效杀细菌的特性。因此,厚朴提取物的有效量可以在以重量计占组合物的约0.005%至约3%的范围内变动。糖果制剂中月桂基硫酸钠的绝对量可以在约4mg至约10mg的范围内变动。
本发明的糖果产品可以是硬糖,咀嚼糖,包衣的含有咀嚼中心的糖(coated chewy center candies)和片状糖。例如,硬糖主要由玉米糖浆和糖组成,其名称来源于其仅含有1.0%-4%的水分的事实。在外观上,这些类型的糖果是固体,但实际上它们是远低于其熔点的超冷液体。硬糖有多种不同类型。玻璃类型的硬糖通常透明或用染料染成不透明;结晶(Grained)类型的硬糖往往不透明。
用糖基制备沉积玻璃类型糖果的连续工艺如下。玉米糖浆在高压蒸气加热的圆筒中伸展。快速热交换导致糖浆中的水蒸发。排出煮过的糖浆,加入色素和香料。将糖浆冷却,沉积在不锈钢的运输装置上。糖浆可以直接被传送至加料斗,通过它糖浆然后直接流入模具。
将糖果运送至决定批样的形状和大小的批样辊(batch rollers)。糖果进入成形装置,所述成形装置使各样品定型成圆盘状,球状,桶状等。本发明可以制成任何形状,圆形,正方形,三角形等,也可以制成动物形状或任何其它可得到的新型模具的形状。然后冷却,包裹,包装糖果。
对于粒状的糖果,将基础组分水和糖与其它组分混合,并在高温(143-155℃,即,约290-310_)下加热,从而导致水变成蒸气。将产品转移至冷却轮,在那里收集了约68kg(约150磅)的批样,置于拉条机中使产品充气,加入香料。
将糖果转移至批样辊,在那里其按一定的大小成形。然后糖果进入成形装置,使各样品定型。糖果在35%的相对湿度下冷却,进入旋转鼓,用精制糖包衣。然后将糖果转移至约32℃(90_),湿度60%的成粒室4小时。室内的空气和湿度导致产品成粒。
作为例子而非限制,下表14中的下列实施例说明了本发明的糖果制剂的多种实施方案。
表14
根据本发明,实施例16-20中的各制剂均添加了上文所述表面活性剂。在一个例示性实施方案中,实施例16-20各包含约0.001%至约2%的表面活性剂。
表15
根据本发明,实施例21-25中的各制剂均添加了上文所述表面活性剂。在一个例示性实施方案中,实施例21-25各包含约0.001%至约2%的表面活性剂。
应该理解的是,对本文所述目前优选的实施方案的各种改变和修饰对本领域技术人员是显而易见的。这些改变和修饰可以在不超出本发明的精神和范围,并且不减少其预期优点的条件下进行。因此希望这些改变和修饰被所附权利要求涵盖。
Claims (25)
1.用于清新消费者口气的口腔用组合物,该口腔用组合物包括:
(a)口腔递送剂;和
(b)抗微生物剂,包括协同比例的厚朴提取物和阴离子表面活性剂,其中协同比例为至少1-4份厚朴提取物对1份阴离子表面活性剂。
2.权利要求1的口腔用组合物,其中阴离子表面活性剂是杀细菌表面活性剂。
3.权利要求1的口腔用组合物,其中阴离子表面活性剂是钠盐。
4.权利要求1的口腔用组合物,其中阴离子表面活性剂是0.001%至2%的月桂基硫酸钠。
5.用于清新消费者口气的口腔用组合物,该口腔用组合物包括:
(a)口腔递送剂;和
(b)抗微生物剂,包括协同比例的厚朴提取物和阴离子表面活性剂,其中协同比例为至少1份厚朴提取物对1份阴离子表面活性剂,其中表面活性剂是月桂基硫酸钠。
6.权利要求5的口腔用组合物,其中厚朴提取物与月桂基硫酸钠的协同比例为2份厚朴提取物对1份月桂基硫酸钠。
7.用于清新消费者口气的口腔用组合物,该口腔用组合物包括:
(a)口腔递送剂;和
(b)抗微生物剂,包括协同比例的厚朴提取物和表面活性剂,其中协同比例为至少1份厚朴提取物对1份表面活性剂,其中表面活性剂是sodium brasslate。
8.用于清新消费者口气的口腔用组合物,该口腔用组合物包括:
(a)口腔递送剂;和
(b)抗微生物剂,包括协同比例的厚朴提取物和表面活性剂,其中协同比例为至少1份厚朴提取物对1份表面活性剂,其中表面活性剂是卵磷脂。
9.权利要求1的口腔用组合物,其中阴离子表面活性剂是三醋酸甘油酯。
10.用于清新消费者口气的口腔用组合物,该口腔用组合物包括:
(a)口腔递送剂;和
(b)抗微生物剂,包括协同比例的厚朴提取物和表面活性剂,其中协同比例为至少1份厚朴提取物对1阴离子份表面活性剂,其中阴离子表面活性剂是月桂醇聚醚硫酸钠。
11.用于清新消费者口气的口腔用组合物,该口腔用组合物包括:
(a)口腔递送剂;和
(b)抗微生物剂,包括协同比例的厚朴提取物和表面活性剂,其中协同比例为至少1份厚朴提取物对1份表面活性剂,其中表面活性剂是甜菜碱。
12.权利要求1的口腔用组合物,其中阴离子表面活性剂是脂肪酸。
13.权利要求1的口腔用组合物,其中阴离子表面活性剂是脂肪酸盐。
14.权利要求1的口腔用组合物,其中阴离子表面活性剂是单酸甘油酯。
15.权利要求1的口腔用组合物,其中阴离子表面活性剂是三酸甘油酯。
16.权利要求1的口腔用组合物,其中阴离子表面活性剂占口腔用组合物的0.001%至1.0%。
17.权利要求1的口腔用组合物,其中口腔递送剂包括口香糖,可食用膜,糖果,牙膏,锭剂和口腔喷雾中的一种。
18.用于清新消费者口气的口腔用组合物,该口腔用组合物包括协同比例的厚朴提取物和表面活性剂,表面活性剂是钠盐,其中协同比例为1-4份厚朴提取物对1份表面活性剂。
19.权利要求18的口腔用组合物,其中表面活性剂是烷基硫酸盐。
20.权利要求19的口腔用组合物,其中表面活性剂是月桂基硫酸钠。
21.权利要求19的口腔用组合物,其中表面活性剂是月桂醇聚醚硫酸钠。
22.权利要求18的口腔用组合物,其中表面活性剂是sodium brasslate。
23.权利要求18的口腔用组合物,其中表面活性剂是月桂酰肌氨酸钠。
24.权利要求18的口腔用组合物,其中表面活性剂占口腔用组合物的0.001%至2%。
25.用于清新消费者口气的口腔用组合物,该口腔用组合物包括协同比例的厚朴提取物和表面活性剂,表面活性剂是钾盐,其中协同比例为1-4份厚朴提取物对1份表面活性剂。
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2005
- 2005-07-14 US US11/181,579 patent/US7632525B2/en not_active Expired - Lifetime
-
2006
- 2006-06-27 EP EP06774132A patent/EP1901704A1/en not_active Ceased
- 2006-06-27 WO PCT/US2006/025042 patent/WO2007011504A1/en active Application Filing
- 2006-06-27 RU RU2008100107/15A patent/RU2388457C2/ru active
- 2006-06-27 AU AU2006270385A patent/AU2006270385B2/en active Active
- 2006-06-27 MX MX2008000563A patent/MX2008000563A/es active IP Right Grant
- 2006-06-27 CN CN2006800256492A patent/CN101222909B/zh active Active
- 2006-06-27 CA CA2614988A patent/CA2614988C/en active Active
-
2009
- 2009-10-20 US US12/582,576 patent/US8163304B2/en active Active
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WO2002091848A1 (en) * | 2001-05-15 | 2002-11-21 | The Procter & Gamble Company | Confectionery compositions |
WO2004000235A2 (en) * | 2002-06-25 | 2003-12-31 | Wm. Wrigley Jr. Company | Breath freshening and oral cleansing product with magnolia bark extract |
Also Published As
Publication number | Publication date |
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RU2388457C2 (ru) | 2010-05-10 |
US20100040564A1 (en) | 2010-02-18 |
AU2006270385B2 (en) | 2010-02-18 |
CN101222909A (zh) | 2008-07-16 |
CA2614988C (en) | 2013-08-06 |
WO2007011504A1 (en) | 2007-01-25 |
US8163304B2 (en) | 2012-04-24 |
AU2006270385A1 (en) | 2007-01-25 |
US20060013779A1 (en) | 2006-01-19 |
RU2008100107A (ru) | 2009-08-20 |
US7632525B2 (en) | 2009-12-15 |
CA2614988A1 (en) | 2007-01-25 |
EP1901704A1 (en) | 2008-03-26 |
MX2008000563A (es) | 2008-03-10 |
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