CN1750809B - 含有药学活性剂的快速溶解的口腔可消耗薄膜 - Google Patents

含有药学活性剂的快速溶解的口腔可消耗薄膜 Download PDF

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CN1750809B
CN1750809B CN200480004745XA CN200480004745A CN1750809B CN 1750809 B CN1750809 B CN 1750809B CN 200480004745X A CN200480004745X A CN 200480004745XA CN 200480004745 A CN200480004745 A CN 200480004745A CN 1750809 B CN1750809 B CN 1750809B
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water
consumable films
batches
mixture
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CN1750809A (zh
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N·M·库尔卡尼
L·D·库玛尔
A·F·索格
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VARNER-LAMBERT Co Ltd
Warner Lambert Co LLC
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Abstract

本发明一般涉及快速溶解的口腔可消耗薄膜，更具体涉及包含药学活性剂的薄膜。

Description

含有药学活性剂的快速溶解的口腔可消耗薄膜
优先权信息
本申请要求美国申请10/423,735的优先权，该申请是US09/395,104的部分继续申请，而US 09/395,104要求美国临时申请60/101,798的优先权。
发明领域
本发明一般涉及快速溶解的口腔可消耗薄膜，更具体涉及包含药学活性剂的薄膜。
相关技术背景
可以制备各种剂型的个人护理产品，包括可食用薄膜组合物的片剂、胶囊、锭剂或带状物。用于口腔的可食用薄膜组合物可以设计用于将治疗试剂递送至口腔粘膜。一个这样的实例是由纽约的PfizerInc.制造的LISTERINEPOCKETPAKSTM商标口腔护理带状产品，它是有效地递送治疗试剂，特别是精油组合物形式的抗菌剂的可食用薄膜组合物的成功实例。
常规的快速溶解口腔可消耗薄膜在用于口腔粘膜的潮湿表面时吸收水，并可能随时间而变得粘稠和胶粘。薄膜的保留可能不足以获得期望的效果，因为薄膜在较短的时间内快速崩解。
有时希望改善对粘膜表面的覆盖和粘附。因此，在本领域中需要开发良好地粘着和保留在口腔粘膜上的可消耗薄膜，以提供用于止咳和粘膜包覆试剂的有效递送和保留系统。
概述
本发明一般涉及一种可消耗薄膜，该可消耗薄膜特别良好地适于在使用者的口中迅速溶解。在本发明的一个具体方面，提供一种适于粘着并溶解在使用者口中的可消耗薄膜，所述薄膜包含至少一种水溶性聚合物、至少一种止咳剂和粘膜包覆有效量的粘膜包覆剂。在一个实施方案中，该粘膜包覆剂为果胶。在本发明的另一方面，本发明提供一种适于粘着并且溶解在使用者口腔中的可消耗薄膜，所述薄膜包含至少一种水溶性聚合物和选自以下的药学活性试剂：阿司匹林、对乙酰氨基酚、布洛芬、酮洛芬、二氟尼柳、非诺洛芬钙、萘普生、托美丁钠、吲哚美辛、氟比洛芬钠、塞来考昔、伐地考昔、罗非考昔及其混合物。
本发明的另一方面涉及一种制备特别适于经口递送至少一种止咳剂的柔软、非自粘着的薄膜的方法。该方法包括制备包含粘膜包覆有效量的粘膜包覆剂的水相；制备包括至少一种水溶性聚合物的成膜混合物；合并水相和成膜混合物以形成水合聚合物凝胶；将该水合聚合物浇铸在衬底上以形成一种浇铸凝胶；和干燥该浇铸凝胶以形成可消耗薄膜，其中将至少一种止咳剂加到水相、水合聚合物凝胶或二者。
发明详述
本发明涉及一种生理可接受的可消耗薄膜，其特别适于溶于使用者的口并粘着在口腔粘膜上。具有粘膜包覆剂的可消耗薄膜特别良好地适于将止咳剂递送至使用者，并用于治疗或缓解与喉痛和/或咳嗽有关的症状和/或刺激。
在本发明的一个方面，本发明提供一种适于粘着并溶于使用者口中的可消耗薄膜，所述薄膜包括至少一种水溶性聚合物、至少一种止咳剂和粘膜包覆有效量的粘膜包覆剂。该粘膜包覆剂能够形成粘着在口和喉的涂层，从而在该可消耗薄膜溶解之后使该止咳剂有效地保留与口和喉的患病区域接触一段时间。
在本发明的另一方面，本发明提供一种适于粘着并且溶解在使用者口腔中的可消耗薄膜，所述薄膜包含至少一种水溶性聚合物和选自以下的药学活性剂：阿司匹林、对乙酰氨基酚、布洛芬、酮洛芬、二氟尼柳、非诺洛芬钙、萘普生、托美丁钠、吲哚美辛、氟比洛芬钠、塞来考昔、伐地考昔、罗非考昔及其混合物。在一个特定的实施方案中，该可消耗薄膜包括药学活性剂，它是数量为大约5至大约20毫克的伐地考昔。
该可消耗薄膜可以包括一种或多种以下成分，这些成分包括但不限于水、抗菌剂、附加的成膜剂或水溶性聚合物、增塑剂、香料、硫沉淀试剂、唾液刺激剂、冷却剂、表面活性剂、稳定剂、乳化剂、增稠剂、粘合剂、着色剂、甘油三酸酯、聚环氧乙烷、丙二醇、增甜剂、香料、防腐剂等，如在1999年9月14日由Leung等人提交的共同未决申请美国专利申请09/395,104中所述，所述文献在此被引用以供参考。
在本发明的另一个实施方案中，该可消耗薄膜包含一单层，该单层包括至少一种水溶性聚合物、至少一种止咳剂和粘膜包覆有效量的果胶。
本文所用的术语“可消耗的”意指包括包含可食用化合物的物质，该物质在施用于使用者时被充分地耐受而没有对使用者造成不适度的副作用或不适。
除非另外特指，所用的术语″wt％″基于最终产品(即可消耗薄膜)而不是用于生产产品的配方的总重，因此它代表主题组分贡献的总干重的百分率。这种理论值可能不同于实验值，因为实际上可消耗薄膜通常保留一些水和/或其它可以用于制备最终产物的物质如醇(例如乙醇)。
在一个实施方案中，将本发明的可消耗薄膜成型并调整大小以对口腔进行给药。该粘膜包覆剂能够赋予该薄膜在溶于使用者口中时的喉咙缓解和包覆性能。该溶解的薄膜粘着在口、通常为口或舌顶的表面，并包覆和粘着在喉咙的粘膜上，从而在其上提供持续长时间的最大保留。结果是，本发明的可消耗薄膜将治疗剂的有效递送和保留系统提供给需要用治疗试剂进行治疗的口腔内的局部区域。
适宜的粘膜包覆剂包括果胶、明胶等以及它们的组合。在一个实施方案中，该粘膜包覆剂可以占可消耗薄膜的大约0.01wt％至大约5wt％，在另一个实施方案中为大约0.1wt％至大约2wt％，在另一个实施方案中为大约0.1wt％至大约1.0wt％的数量范围存在。
适宜的止咳剂包括阿洛拉胺、阿米西酮、苯丙哌林、苯佐那酯、比苯溴铵、溴仿、布他米酯、布替他酯、乙二磺酸卡拉美芬、卡拉美芬乙二磺酸盐、喷托维林、氯苯达诺、氯丁替诺、氯哌斯汀、可待因、溴甲可待因、可待因N-氧化物、磷酸可待因、硫酸可待因、环沙酮、右美沙芬、双叔丁萘磺酸钠、双氢可待因、醋氢可待酮、二甲啡烷、地美索酯、V，V-二苯基-2-哌啶丙醇、羟丙哌嗪、羟蒂巴酚、依普拉酮、双叔丁萘磺酸乙酯、乙基吗啡、福米诺苯、愈创哌特、氢可酮、异米尼尔、左丙氧芬、吗氯酮、那碎因、去甲美沙酮、那可丁、奥昔拉定、奥索拉明、福尔可定、匹考哌林、匹哌氮酯、哌啶酮、盐酸普诺地嗪、消旋甲啡烷、盐酸他齐普酮、替培啶、齐培丙醇等及其可药用盐以及它们的组合。本发明中所用的止咳剂可以是游离的形式或任何保持它们治疗活性的无毒可药用的形式。在一个实施方案中，该止咳剂为氢溴酸右美沙芬。
该止咳剂是单一的止咳剂或其组合，以有效的量使用。“有效量”是足以至少减少咳嗽和/或喉痛不良影响发生，但低至足以避免任何不良副作用发生的数量。除了所选择的特定止咳剂或试剂之外，止咳剂的有效量可以随咳嗽症状的类型和/或严重程度、被治疗的患者的年龄和生理状况、治疗持续时间、同时治疗的类型、所用止咳剂的特定形式(例如盐)和包含止咳剂的可消耗薄膜的特定配方而变。这些改变可以由本领域技术人员容易地确定。
将止咳剂的数量调节至在预定的时间内递送预定剂量的止咳剂，该时间可以典型地为4-24小时，更典型为大约每12小时。典型的止咳剂的成人剂量包含大约1至大约130mg，优选大约2.5mg至大约65mg，更优选大约2.5至大约20，最优选大约15mg的止咳剂(例如氢溴酸右美沙芬)。典型的止咳剂的儿童剂量包含大约2.5至大约10mg，更优选大约7.5mg的氢溴酸右美沙芬。
除非另外指出，本发明的可消耗薄膜中的止咳剂的数量可以在将“湿”薄膜配方干燥并形成可消耗薄膜之后指定为wt％。一般地，用于可消耗薄膜的止咳剂的数量为可消耗薄膜总重的大约0.01％至大约80wt％，优选大约2.5％至大约40wt％，更优选大约5％至大约30wt％。
薄膜可以测量为大约1至大约1.25(2.54cmx3.18cm)和重约60mg至约190mg。
可以将有效地治疗除咳嗽之外的症状的附加治疗剂加到本发明的各个实施方案中，例如抗组胺剂，拟交感神经药学活性剂(鼻减充血剂、支气管扩张剂)，镇痛剂、抗炎剂、咳嗽祛痰剂等，如在1999年9月14日由Leung等人提交的共同未决申请美国专利申请09/395,104所述，所述文献在此被引用以供参考。这些附加治疗试剂的其它实例在本领域中是已知的。
有用的抗组胺剂包括西替利嗪、苯海拉明、氯雷他定、去氯雷他定、非索非那定、孟鲁司特钠等。
在表A中评述了用于可以在一快速溶解的口腔薄膜的带状物中递送的特定药学活性试剂的剂量的实例。
表A
  药学活性剂   剂量
  马来酸氯苯那敏   4-12mg
  马来酸溴苯那敏   4mg
  右氯苯那敏   2mg
  右溴苯那敏   2mg
  盐酸曲普利啶   2.5mg
  药学活性剂   剂量
  西替利嗪   5-10mg
  阿伐斯汀   8mg
  马来酸阿扎他定   1mg
  氯雷他定   5-10mg
  盐酸苯福林   5-10mg
  氢溴酸右美沙芬   10-30mg
  西地那非   25-100mg
  酮洛芬   12.5-25mg
  丁二酸舒马普坦   35-70mg
  佐米曲坦   2.5mg
  洛哌丁胺   2mg
  法莫替丁   5-10mg
  尼古丁   1-15mg
  盐酸苯海拉明   12.5-25mg
  盐酸伪麻黄碱   15-60mg
  阿托伐他汀   5-80mg
  伐地考昔   5-20mg
  苯磺酸氨氯地平   2.5-10mg
  罗非考昔   5-25mg
  盐酸舍曲林   10-100mg
  齐拉西酮   20-80mg
  依来曲普坦   10-40mg
  药学活性剂   剂量
  硝酸甘油   0.3-0.6mg
本发明的薄膜组合物还可以用于提供营养学可接受的组分，例如维生系、矿物质、微量元素和纤维(优选可溶纤维)。
适于引入本发明组合物的维生素的实例包括药学或营养学可接受形式的维生素A、维生素D、维生素E、维生素K、维生素C、叶酸、硫胺素、核黄素、维生素B(6)、维生素B(12)、烟酸、生物素和泛酸。适于引入本发明组合物的矿物元素和痕量元素实例包括药学或营养学可接受形式的钙、钠、钾、磷、镁、锰、铜、锌、铁、硒、铬和钼。
本文所用的术语纤维指能在结肠中基本上发生发酵以产生短链脂肪酸的纤维。适宜的可溶纤维的实例包括carubin、果胶、黄蓍胶、谷类β-葡聚糖等。它们可以被水解或未被水解。
表现成膜性能的有用的水溶性聚合物包括支链淀粉(pullulan)、羟丙基甲基纤维素、羟乙基纤维素、羟丙基纤维素、聚乙烯吡咯烷酮、羧甲基纤维素、聚乙烯醇、藻酸钠、聚乙二醇、黄蓍胶、瓜尔胶、金合欢胶(acacia gum)、阿拉伯胶(arabic gum)、聚丙烯酸、甲基丙烯酸甲酯共聚物、羧基乙烯基聚合物、直链淀粉、高直链淀粉、羟丙基化高直链淀粉、糊精、壳多糖、壳聚糖、果聚糖、痂囊腔菌聚糖、胶原、玉米醇溶蛋白、谷蛋白、大豆蛋白分离物、乳清蛋白分离物、酪蛋白及其组合。在本发明的一个实施方案中，该薄膜包含支链淀粉作为水溶性聚合物。水溶性聚合物的数量一般为可消耗薄膜的大约0.01wt％至大约99wt％，优选大约30wt％至大约80wt％，更优选大约45％至大约70wt％，最优选占可消耗薄膜的大约60wt％至大约65wt％。
在本发明的另一个实施方案中，该可消耗薄膜还可以包含抗菌剂，包括但不限于如在1999年9月14日由Leung等人提交的共同未决美国专利申请09/395,104中所述的精油，所述文献在此被引用以供参考。有用的精油香芹酚、百里酚、桉油精、薄荷醇、水杨酸甲酯、丁香酚、gerianol、马鞭草烯酮等及其组合。用于本发明的一种优选的精油的组合用在商标漱口药和口护理带状物，它是已知的证明有效地杀死口腔内促使形成噬斑、龈炎和口臭的微生物的抗菌口腔组合物的实例。
精油包括精确平衡量的具有抗菌活性的百里酚、水杨酸甲酯、薄荷醇和桉油精(下文“优选的精油”)。
用于本发明的可消耗薄膜的精油的量可以改变，只要它们的数量足以提供抗菌效力。一般地，精油的数量为可消耗薄膜的至多大约30wt％，优选大约0.05wt％至大约18wt％。在一个优选的实施方案中，百里酚、水杨酸甲酯和桉油精的量分别为可消耗薄膜的大约0.01wt％至大约4wt％，优选大约0.05wt％至大约3.0wt％，更优选大约0.07wt％至大约2.0wt％。薄荷醇可以组合物的大约0.01wt％至大约15wt％，优选为可消耗薄膜的大约2.0wt％至大约9.0wt％，更优选大约3wt％至大约9wt％的数量存在。在某些实施方案中，合并提供协同增强抗菌性能以消灭引起牙齿噬菌斑、龈炎和口臭的产生噬菌斑的微生物的量的精油。
关于加入精油的实施方案，由于该可消耗薄膜中油含量较高因而要避免使用湿润剂，以避免产生过度湿润、自粘连的薄膜。在一个实施方案中，该可消耗薄膜包括还作为湿润剂的非甘油增塑剂，并含有作为轻度湿润剂的非山梨醇增甜剂。
还可以将唾液刺激剂加到本发明的可消耗薄膜。有用的唾液刺激剂公开在美国专利4,820,506中，所述文献在此被全文引用以供参考。
适宜的增甜剂包括天然和人造增甜剂，例如A)水溶性增甜剂，包括单糖、二糖、多糖等，B)水溶性人造增甜剂，包括可溶的糖精盐等，C)基于二肽的增甜剂，例如L-天冬氨酸衍生的增甜剂，包括阿斯巴甜、纽甜(neotame)等，D)天然存在的水溶性增甜剂的衍生物，包括蔗糖的氯化衍生物、Sucralose等，E)基于蛋白增甜剂，包括thauma toccousdanielli(竹芋蛋白I和II)等，以及它们的组合。
一般地，使用有效量的辅助增甜剂以提供特定组合物所需的甜度，且这种数量随所选择的特定增甜剂而变。当使用容易提取的增甜剂时，有效量一般为可消耗薄膜的大约0.01wt％至大约10wt％。水溶性增甜剂的常用量为可消耗薄膜的大约0.01wt％至大约10wt％，优选用量为大约2.0wt％至大约5.0wt％。除了水溶性增甜剂之外的上述其它增甜剂的常用量为可消耗薄膜的大约0.01wt％至大约10wt％，优选大约2wt％至大约8wt％，更优选大约3wt％至大约6wt％。
还可以将防腐剂加到该可消耗薄膜。防腐剂的加入量为可消耗薄膜的大约0.001wt％至大约5％，优选大约0.01wt％至大约1wt％。优选的防腐剂包括苯甲酸钠、山梨酸钾等以及它们的组合。其它适宜的防腐剂包括但不限于依地酸盐(还已知为乙二胺四乙酸盐或EDTA，例如二钠EDTA)。
本发明的另一个实施方案涉及制备本发明的可消耗薄膜的方法。一般地，将至少一种止咳剂和粘膜包覆有效量的粘膜包覆剂溶于水以形成水相。水相还可以包括增甜剂、染料等。制备包含至少一种水溶性聚合物(例如支链淀粉(pullulan))的成膜混合物。将水相和成膜混合物合并，并充分混合以形成水合聚合物凝胶。任选地，可以将包含有机成分如精油和其它油(例如甘油、橄榄油)香料、表面活性剂(例如聚山梨酸酯80、Atmos 300、Atsurf 596K)等的有机相与水相、成膜混合物或水合聚合物凝胶混合。所得的水合聚合物凝胶为用于形成浇铸凝胶的在适宜的衬底上的铸型。将所得的水合聚合物凝胶浇铸在适宜的衬底上以形成浇铸造凝胶。然后将该浇铸凝胶干燥形成可消耗薄膜。
在另一个实施方案中，本发明提供一种制备可消耗薄膜的方法，它可能期望首先通过使水溶性聚合物与水合而首先形成成膜混合物。然后通过将其它水溶性成分如止咳剂、粘膜包覆剂(例如果胶)，增甜剂、染料等溶于水来制备水相。分别地，将有机成分如精油和其它油(例如甘油、橄榄油)香料、表面活性剂(例如聚山梨酸酯80、Atmos 300、Atsurf 596K)等混合在一起。然后通过将该成膜聚合物相与水相混合，然后加入有机相来生产最终的配方。将合并的混合物形成一种乳液或水合聚合物凝胶。
然后将所得的水合聚合物凝胶浇铸在适宜的衬底上，并干燥形成一种薄膜。优选将该可消耗薄膜风干，在热空气下干燥，并切成期望的尺寸，包装并储存。该包装的薄膜可以包含数量为大约0.1wt％至大约10wt％，更优选大约4wt％至大约7wt％的湿气。
成膜混合物还可以包括稳定剂如黄原胶、豆角胶、角叉菜胶等以及它们的组合。将这些成分混合，然后在温水，优选去离子水中水合，直至形成凝胶，这可能要耗时大约30小时至大约48小时。优选将水加热至大约20℃至大约40℃的温度以促进水合。水的数量通常为凝胶的大约40wt％至大约80wt％。然后将所得的水合凝胶冷却至大约20℃至大约30℃的温度，持续大约1小时至大约48小时。
除了止咳剂和粘膜包覆有效量的粘膜包覆剂如果胶之外，该水相可以包括添加剂如着色剂、葡萄糖酸铜和增甜剂。通常水相包含占最终凝胶混合物总重的大约5wt％至大约80wt％。
如果在配方中使用作为选择的增甜剂的糖精钠和作为选择的硫沉淀剂的葡萄糖酸铜，则优选分别将它们溶于溶液以避免沉淀。
在本发明的另一个实施方案中，该水溶性聚合物为粉末的形式，其加到水相形成水合聚合物凝胶。将所得的水合聚合物凝胶在大约室温下充分搅拌大约30分钟至大约48小时，然后除气以除去至少基本上全部的空气气泡。将该均一的混合物浇铸在适宜的衬底上，然后干燥形成期望的薄膜。
关于包含精油的可消耗薄膜，还将精油加到有机相，并将该有机相与水合聚合物凝胶混合。特别地，可以任选将精油如薄荷醇和百里酚与油混合形成一种油混合物。将其它精油如水杨酸甲酯和桉油精和表面活性剂加到油混合物。然后将该油混合物加到水合聚合物凝胶，并混合至形成均一的凝胶。然后将该均一的凝胶浇铸在适宜的衬底上，然后干燥形成该可消耗薄膜。
在制备可消耗薄膜的一个实施方案中，可以在不加热水的情况下将水溶性聚合物水合以降低制造过程中的能量成本。而且，由于加热可能导致不期望的挥发性成分损失蒸发，因此优选在水合过程中避免加热。关于含精油薄膜，加热还可能由于精油的损失而影响组合物的杀菌活性。
在不意在受任何理论限制的情况下，据信可以将成膜成分如水溶性聚合物水合，并且由于存在已知为Donnan平衡的离子效应而在不加热的情况下混合。在电解质存在下在溶液中将水溶性聚合物水合有效地降低正在形成的聚合物凝胶的粘性，从而增加水合过程的效率。该配方的水溶性成分提供电解质，其在加到水溶性聚合物之前溶于水合溶液。高度剪切混合也加速水合，使粉末去团块化，从而提供更大的水接触表面积。此外，在剪切区域产生的局部加热效应提供水合的能量而基本上不用升高物质的温度。
实施例1
根据以下方法将表1所列的成分合并以提供本发明的可消耗薄膜：
A)75℃下将右美沙芬HBr混合并溶于90％水得到水相。将Amberlite IRP69加到水相，并在大约70℃至80℃下搅拌大约4-5小时。非常缓慢地将果胶加到水相，并在高速下混合。将水相冷却至大约50℃，并加入适量的水以替代由于蒸发导致的损失。然后将山梨酸钾、增甜剂和染料加到水相，并充分混合。
B)在单独的容器中将成膜成分、黄原胶、刺槐豆胶、角叉菜胶和支链淀粉混合在一起以形成一种成膜混合物。
C)将该成膜混合物缓慢地加到A)的水相，然后慢速混合过夜以提供水合聚合物凝胶。
D)将香料、甘油、薄荷醇和表面活性剂合并，并在单独的容器中混合至溶解得到一种有机相。
E)在单独的容器中于剩余的10％水中将甘露醇混合在一起。然后将多汁(succulence)加到所得的混合物并溶解。
F)将步骤D)和E)的混合物加到水合聚合物凝胶，并均一地混合得到最终的聚合物凝胶混合物。将该最终的聚合物凝胶混合物浇注在模具上，并在室温下浇铸形成期望厚度的薄膜。将该可消耗薄膜在温热空气下干燥，并切成期望的尺寸(例如由剂量和口感来确定)。将该可消耗薄膜分割成1″x 1.25″(2.54cmx3.18cm)剂量单元，各单元的厚度为0.009±0.002英寸(0.23±0.05mm)，重70±3mg。
表1
  材料   mg/剂*   ％w/w*干燥薄膜   ％w/w实际批量   g/批量
  右美沙芬HBr   15.0000   22.3940   7.6539   38.2695
  Amberlite IRP69   16.0000   23.8870   8.1642   40.8208
  果胶USP   0.3500   0.5225   0.1786   0.8930
  黄原胶   0.0766   0.1165   0.0396   0.1980
  刺槐豆胶   0.0901   0.1345   0.0460   0.2299
  角叉菜胶   0.3861   0.5764   0.1970   0.9851
  支链淀粉   20.5919   30.7424   10.5072   52.5361
  山梨酸钾   0.0772   0.1153   0.0394   0.1970
  乙酰舒泛钾盐   0.6435   0.9607   0.3284   1.6418
  天冬酰苯丙氨酸甲酯NF   1.8018   2.6900   0.9194   4.5969
  纯化水   -   -   65.8217   329.1085
  薄荷醇   2.5740   3.8428   1.3134   6.5670
  薄荷香料   0.2579   0.3850   0.1316   0.6580
  樱桃香料(Givudan)   0.2579   0.3850   0.1316   0.6580
  樱桃香料混合物(IFF)   2.2350   3.3367   1.1404   5.7022
  Warm Sensation(Mane)   0.5518   0.8238   0.2816   1.4078
  人造掩味剂(Robertet)   0.4139   0.6179   0.2112   1.0560
  多汁(IFF)   0.2579   0.3850   0.1316   0.6580
  材料   mg/剂*   ％w/w*干燥薄膜   ％w/w实际批量   g/批量
  FD&C Red#40   0.0102   0.0152   0.0052   0.0260
  聚山梨酸酯80NF   0.4504   0.6724   0.2298   1.1491
  Atmos 300   0.4504   0.6724   0.2298   1.1491
  甘油   1.9305   2.8821   0.9851   4.9253
  甘露醇USP   2.5740   3.8428   1.3134   6.5670
  总量   66.9821   100.0000   100.0000   500.0000
  *假定所有的水蒸发
实施例2
根据以下方法将表2所列的成分合并以提供本发明的可消耗薄膜：
A)75℃下将右美沙芬HBr混合并溶于90％水得到水相。将Amberlite IRP64加到水相，并在大约70℃至80℃下搅拌大约4-5小时。将果胶与甘油混合，并将混合物非常缓慢地加到水相，然后在高速下混合。将水相冷却至大约50℃，并加入适量的水以代替由于蒸发导致的损失。然后将山梨酸钾和染料加到水相，并充分混合。
B)在单独的容器中将成膜成分、黄原胶、刺槐豆胶、角叉菜胶和支链淀粉混合在一起以形成一种成膜混合物。
C)将该成膜混合物缓慢地加到A)的水相，然后慢速混合过夜以提供水合聚合物凝胶。
D)将香料和薄荷醇合并，并在单独的容器中混合至溶解得到一种有机相。
E)在单独的容器中于剩余的10％水中将甘露醇和Sucralose混合在一起。然后将多汁加到所得的混合物并溶解。
F)将步骤D)和E)的混合物加到水合聚合物凝胶，并均一地混合得到最终的聚合物凝胶混合物。将该最终的聚合物凝胶混合物浇注在模具上，并在室温下浇铸形成期望厚度的薄膜。将该可消耗薄膜在温热空气下干燥，并切成期望的尺寸(例如由剂量和口感来确定)。将该可消耗薄膜分割成1″x 1.25″(2.54cmx3.18cm)剂量单元，各单元的厚度为0.009±0.002英寸(0.23±0.05mm)，重70±3mg。
表2
  材料   mg/剂*   ％w/w*干燥薄膜   ％w/w实际批量   g/批量
  右美沙芬HBr   15.0000   22.9235   7.8353   39.1765
  Amberlite IRP 64   16.0000   24.4518   8.3576   41.7882
  材料   mg/剂*   ％w/w*干燥薄膜   ％w/w实际批量   g/批量
  果胶USP   0.3500   0.5349   0.1828   0.9141
  黄原胶   0.0769   0.1175   0.0402   0.2008
  刺槐豆胶   0.0901   0.1377   0.0471   0.2353
  角叉菜胶   0.3861   0.5901   0.2017   1.0084
  支链淀粉   20.5919   31.4693   10.7562   53.7812
  山梨酸钾   0.0772   0.1180   0.0403   0.2016
  纯化水    -   -   65.8199   329.0995
  薄荷醇   2.5740   3.9337   1.3445   6.7227
  薄荷香料   0.2579   0.3941   0.1347   0.6736
  樱桃香料(Givudan)   0.2579   0.3941   0.1347   0.6736
  酸樱桃(IFF)   2.2350   3.4156   1.1675   5.8373
  Warm Sensation(Mane)   0.5518   0.8433   0.2882   1.4412
  人造掩味剂(Robertet)   0.4139   0.6325   0.2162   1.0810
  多汁(IFF)   0.2579   0.3941   0.1347   0.6736
  FD&C Red#40   0.0098   0.0150   0.0051   0.0256
  甘油   1.9305   2.9503   1.0084   5.0420
  甘露醇USP   2.5740   3.9337   1.3445   6.7227
  三氯蔗糖   1.8000   2.7508   0.9402   4.7012
  总量   65.4349   100.0000   100.0000   500.0000
  *假定所有的水蒸发
实施例3
根据实施例1的方法将表3的成分合并以提供本发明的可消耗薄膜。
表3
  材料   mg/剂*   ％w/w*干燥薄膜   ％w/w实际批量   g/批量
  右美沙芬HBr   15.0000   22.6123   7.7289   38.6445
  Amberlite  IRP69   16.0000   24.1197   8.2442   41.2208
  果胶USP   0.3500   0.5276   0.1803   0.9017
  黄原胶   0.0769   0.1159   0.0396   0.1981
  刺槐豆胶   0.0901   0.1358   0.0464   0.2321
  角叉菜胶   0.3861   0.5820   0.1989   0.9947
  支链淀粉   20.5919   31.0420   10.6102   53.0509
  山梨酸钾   0.0772   0.1164   0.0398   0.1989
  纯化水   -   -   65.8199   329.0995
  薄荷醇   2.5740   3.8803   1.3263   6.6314
  薄荷香料   0.2579   0.388   0.1329   0.6644
  樱桃香料(Givudan)   0.2579   0.388   0.1329   0.6644
  樱桃香料混合物(IFF)   2.2350   3.3692   1.1516   5.7580
  Warm Sensation(Mane)   0.5518   0.8318   0.2843   1.4216
  人造掩味剂(Robertet)   0.4139   0.6239   0.2133   1.0663
  多汁(IFF)   0.2579   0.3888   0.1329   0.6644
  FD&C Red#40   0.0098   0.0148   0.0050   0.0252
  聚山梨酸酯80NF   0.4504   0.6790   0.2321   1.1604
  Atmos  300   0.4504   0.6790   0.2321   1.1604
  甘油   1.9305   2.9102   0.9947   4.9735
  甘露醇USP   2.5740   3.8803   1.3263   6.6314
  三氯蔗糖   1.8000   2.7135   0.9275   4.6373
  材料   mg/剂*   ％w/w*干燥薄膜   ％w/w实际批量   g/批量
  总量   66.3357   100.0000   100.0000   500.0000
  *假定所有的水蒸发
实施例4
根据实施例2的方法，除了在步骤D还将甘油和表面活性剂加到香料和薄荷醇中，将表4所列的成分合并以提供一种可消耗薄膜。
表4
  材料   mg/剂*   ％w/w*干燥薄膜   ％w/w实际批量   g/批量
  右美沙芬HBr   15.0000   22.6123   7.7289   38.6445
  Amberlite IRP64   16.0000   24.1197   8.2442   41.2208
  果胶USP   0.3500   0.5276   0.1803   0.9017
  黄原胶   0.0769   0.1159   0.0396   0.1981
  刺槐豆胶   0.0901   0.1358   0.0464   0.2321
  角叉菜胶   0.3861   0.5820   0.1989   0.9947
  支链淀粉   20.5919   31.0420   10.6102   53.0509
  山梨酸钾   0.0772   0.1164   0.0398   0.1989
  纯化水   -   -   65.8199   329.0995
  薄荷醇   2.5740   3.8803   1.3263   6.6314
  薄荷香料   0.2579   0.3888   0.1329   0.6644
  樱桃香料(Givudan)   0.2579   0.3888   0.1329   0.6644
  酸樱桃(IFF)   2.2350   3.3692   1.1516   5.7580
  Warm Sensation(Mane)   0.5518   0.8318   0.2843   1.4216
  人造掩味剂(Robertet)   0.4139   0.6239   0.2133   1.0663
  材料   mg/剂*   ％w/w*干燥薄膜   ％w/w实际批量   g/批量
  多汁(IFF)   0.2579   0.3888   0.1329   0.6644
  FD&C Red#40   0.0098   0.0148   0.0050   0.0252
  聚山梨酸酯80NF   0.4504   0.6790   0.2321   1.1604
  Atmos 300   0.4504   0.6790   0.2321   1.1604
  甘油   1.9305   2.9102   0.9947   4.9735
  甘露醇USP   2.5740   3.8803   1.3263   6.6314
  三氯蔗糖   1.8000   2.7135   0.9275   4.6373
  总量   66.3357   100.0000   100.0000   500.0000
  *假定所有的水蒸发
实施例5
根据以下方法将表5所列的成分合并以提供本发明的可消耗薄膜：
A)75℃下将右美沙芬HBr混合并溶于90％水得到水相。将Amberlite IRP69加到水相，并在大约70℃至80℃下搅拌大约4-5小时。将果胶非常缓慢地加到水相并以高混合速度混合。将水相冷却至大约50℃，并加入适量的水以代替由于蒸发导致的损失。然后将山梨酸钾和染料加到水相，并充分混合。
B)在单独的容器中将成膜成分、黄原胶、刺槐豆胶、角叉菜胶和PURE-COTETM(购自Grain Processing Corporation of Muscatine，lowa)混合在一起以形成一种成膜混合物。
C)将该成膜混合物缓慢地加到A)的水相，然后以缓慢混合速率混合过夜以提供水合聚合物凝胶。
D)将香料、甘油、橄榄油、薄荷醇和表面活性剂合并，并在单独的容器中混合至溶解得到一种有机相。
E)在单独的容器中于剩余的10％水中将甘露醇和Sucralose混合在一起。然后将多汁加到所得的混合物并溶解。
F)将步骤D)和E)的混合物加到水合聚合物凝胶，并均一地混合得到最终的聚合物凝胶混合物。将该最终的聚合物凝胶混合物浇注在模具上，并在室温下浇铸形成期望厚度的薄膜。将该可消耗薄膜在温热空气下干燥，并切成期望的尺寸(例如由剂量和口感来确定)。将该可消耗薄膜分割成1″x 1.25″(2.54cmx3.18cm)剂量单元，各单元的厚度为0.009±0.002英寸(0.23±0.05mm)，重70±3mg。
表5
  材料   mg/剂*   ％w/w*干燥薄膜   ％w/w实际批量   g/批量
  右美沙芬HBr   15.0000   19.5740   10.6759   106.7593
  Amberlite IRP69   16.0001   20.8790   11.3877   113.8771
  果胶USP   0.3499   0.4566   0.2490   2.4905
  黄原胶   0.0769   0.1003   0.0547   0.5470
  刺槐豆胶   0.0901   0.1175   0.0641   0.6409
  角叉菜胶   0.3860   0.5037   0.2747   2.7474
  PURE-COTE<sup>TM</sup>B793   20.5919   26.8711   14.6559   146.5586
  山梨酸钾   0.0772   0.1008   0.0550   0.5498
  纯化水   -   -   45.4586   454.5856
  薄荷醇   2.5740   3.3589   1.8320   18.3202
  薄荷香料   0.2579   0.3366   0.1836   1.8357
  樱桃香料(Givudan)   0.2579   0.3366   0.1836   1.8357
  酸樱桃(IFF)   2.2350   2.9165   1.5907   15.9070
  Warm Sensation(Mane)   0.5518   0.7200   0.3927   3.9270
  人造掩味剂(Robertet)   0.4140   0.5402   0.2946   2.9463
  多汁(IFF)   0.2579   0.3366   0.1836   1.8357
  FD&C Red#40   0.0099   0.0129   0.0070   0.0704
  聚山梨酸酯80NF   0.4505   0.5878   0.3206   3.2060
  Atmos  300   0.4505   0.5878   0.3206   3.2060
  甘油   8.7335   11.3966   6.2158   62.1585
  橄榄油   3.49934   4.5586   2.4863   24.8634
  甘露醇USP   2.5740   3.3589   1.8320   18.3202
  材料   mg/剂*   ％w/w*干燥薄膜   ％w/w实际批量   g/批量
  三氯蔗糖   1.8001   2.3490   1.2812   12.8116
  总量   76.6324   100.0000   100.0000   1000.0000
  *假定所有的水蒸发
实施例6
根据实施例5的方法，除了在步骤A)中加到水相之前将果胶分散在15％甘油中，将表6所列的成分合并以提供一种可消耗薄膜。
表6
  材料   mg/剂*   ％w/w*干燥薄膜   ％w/w实际批量   g/批量
  右美沙芬HBr   15.0000   18.5409   10.3611   103.6107
  Amberlite IRP69   16.0001   19.7771   11.0519   110.5186
  果胶USP   0.3499   0.4325   0.2417   2.4170
  黄原胶   0.0769   0.0950   0.0531   0.5309
  刺槐豆胶   0.0901   0.1113   0.0622   0.6220
  角叉菜胶   0.3860   0.4771   0.2666   2.6664
  PURE-COTE<sup>TM</sup>B793   20.5919   25.4529   14.2236   142.2363
  山梨酸钾   0.0772   0.0955   0.0534   0.5335
  纯化水   -   -   44.1179   451.1788
  薄荷醇   2.5740   3.1817   1.7780   17.7799
  薄荷香料   0.2579   0.3188   0.1782   1.7816
  樱桃香料(Givudan)   0.2579   0.3188   0.1782   1.7816
  酸樱桃(IFF)   2.2350   2.7626   1.5438   15.4379
  Warm Sensation(Mane)   0.5518   0.6820   0.3811   3.8112
  人造掩味剂(Robertet)   0.4140   0.5117   0.2859   2.8594
  材料   mg/剂*   ％w/w*干燥薄膜   ％w/w实际批量   g/批量
  多汁(IFF)   0.2579   0.3188   0.1782   1.7816
  FD&C Red#40   0.0099   0.0122   0.0068   0.0684
  聚山梨酸酯80NF   0.4505   0.5568   0.3111   3.1114
  Atmos 300   0.4505   0.5568   0.3111   3.1114
  甘油   11.6446   14.3935   8.0434   80.4337
  橄榄油   4.8519   5.9973   3.3514   33.5140
  甘露醇USP   2.5740   3.1817   1.7780   17.7799
  三氯蔗糖   1.8001   2.2250   1.2434   12.4337
  总量   80.9021   100.0000   100.0000   1000.0000
  *假定所有的水蒸发
实施例7
根据以下方法将表7所列的成分合并以提供本发明的可消耗薄膜：
A)75℃下将右美沙芬HBr混合并溶于90％水得到水相。将Amberlite IRP69加到水相，并在大约70℃至80℃下搅拌大约4-5小时。将分散在甘油中的果胶非常缓慢地加到水相并以高混合速度混合。将水相冷却至大约50℃，并加入适量的水以替代由于蒸发导致的损失。然后将山梨酸钾和染料加到水相，并充分混合。
B)在单独的容器中将成膜成分、黄原胶、刺槐豆胶、角叉菜胶和支链淀粉混合在一起以形成一种成膜混合物。
C)将该成膜混合物缓慢地加到A)的水相，然后以缓慢混合速率混合过夜以提供水合聚合物凝胶。
D)在单独的容器中将香料、薄荷醇和表面活性剂合并并混合至溶解得到一种有机相。
E)在单独的容器中于剩余的10％水中将甘露醇和Sucralose混合在一起。然后将多汁加到所得的混合物并溶解。
F)将步骤D)和E)的混合物加到水合聚合物凝胶，并均一地混合得到最终的聚合物凝胶混合物。将该最终的聚合物凝胶混合物浇注在模具上，并在室温下浇铸形成期望厚度的薄膜。将该可消耗薄膜在温热空气下干燥，并切成期望的尺寸(例如由剂量和口感来确定)。
表7
  材料   mg/剂*   ％w/w*干燥薄膜   ％w/w实际批量   g/批量
  右美沙芬HBr   15.0000   22.5510   7.7080   19.2699
  Amberlite IRP64   16.0000   24.0544   8.2218   20.5545
  果胶USP   0.3500   0.5262   0.1799   0.4496
  黄原胶   0.0769   0.1156   0.0395   0.0988
  刺槐豆胶   0.0901   0.1355   0.0463   0.1157
  角叉菜胶   0.3861   0.5805   0.1984   0.4960
  支链淀粉   20.5919   30.9579   10.5814   26.4536
  山梨酸钾   0.0772   0.1161   0.0397   0.0992
  纯化水   -   -   65.8199   164.5498
  薄荷醇   2.5740   3.8698   1.3227   3.3067
  薄荷香料   0.2579   0.3877   0.1325   0.3313
  樱桃香料(Givudan)   0.2579   0.3877   0.1325   0.3313
  酸樱桃(IFF)   2.2350   3.3601   1.1485   2.8712
  Warm Sensation(Mane)   0.5518   0.8296   0.2835   0.7089
  人造掩味剂(Robertet)   0.4139   0.6223   0.2127   0.5317
  多汁(IFF)   0.2579   0.3877   0.1325   0.3313
  胭脂红   0.1900   0.2856   0.0976   0.2441
  聚山梨酸酯80NF   0.4504   0.6771   0.2314   0.5786
  Atsurf 596K   0.4504   0.6771   0.2314   0.5786
  甘油   1.9305   2.9023   0.9920   2.4800
  甘露醇USP   2.5740   3.8698   1.3227   3.3067
  三氯蔗糖   1.8000   2.7061   0.9250   2.3124
  材料   mg/剂*   ％w/w*干燥薄膜   ％w/w实际批量   g/批量
  总量   66.5159   100.0000   100.0000   250.0000
  *假定所有的水蒸发
实施例8
根据实施例7的方法，将表8所列的成分合并以提供一种可消耗薄膜。
表8
  材料   mg/剂*   ％w/w*干燥薄膜   ％w/w实际批量   g/批量
  右美沙芬HBr   15.0000   22.5772   7.7169   38.5846
  Amberlite IRP64   16.0000   24.0823   8.2314   41.1569
  果胶USP   0.3500   0.5268   0.1801   0.9003
  黄原胶   0.0769   0.1157   0.0396   0.1978
  刺槐豆胶   0.0901   0.1356   0.0464   0.2318
  角叉菜胶   0.3861   0.5811   0.1986   0.9932
  支链淀粉   20.5919   30.9938   10.5937   52.9686
  胭脂红   0.1900   0.2860   0.0977   0.4887
  纯化水   -   -   65.8199   329.0995
  薄荷醇   2.5740   3.8742   1.3242   6.6211
  薄荷香料   0.2579   0.3882   0.1327   0.6634
  樱桃香料(Givudan)   0.2579   0.3882   0.1327   0.6634
  酸樱桃(IFF)   2.2350   3.3640   1.1498   5.7491
  Warm Sensation(Mane)   0.5518   0.8305   0.2839   1.4194
  人造掩味剂(Robertet)   0.4139   0.6230   0.2129   1.0647
  多汁(IFF)   0.2579   0.3882   0.1327   0.6634
  材料   mg/剂*   ％w/w*干燥薄膜   ％w/w实际批量   g/批量
  聚山梨酸酯80NF   0.4504   0.6779   0.2317   1.1586
  Atmos  300   0.4504   0.6779   0.2317   1.1586
  甘油   1.9305   2.9057   0.9932   4.9658
  甘露醇USP   2.5740   3.8742   1.3242   6.6211
  三氯蔗糖   1.8000   2.7093   0.9260   4.6301
  总量   66.4387   100.0000   100.0000   500.0000
  *假定所有的水蒸发
实施例9
根据以下方法将表9所列的成分合并以提供本发明的可消耗薄膜：
A)将右美沙芬HBr混合并溶于90％水得到水相。将分散在甘油中的果胶非常缓慢地加到水相并以高混合速度混合。将水相冷却至大约50℃，并加入适量的水以替代由于蒸发导致的损失。然后将染料加到水相，并充分混合。
B)在单独的容器中将成膜成分、黄原胶、刺槐豆胶、角叉菜胶和支链淀粉混合在一起以形成一种成膜混合物。
C)将该成膜混合物缓慢地加到A)的水相，然后以缓慢混合速率混合过夜以提供水合聚合物凝胶。
D)在单独的容器中将香料、薄荷醇和表面活性剂合并并混合至溶解得到一种有机相。
E)在单独的容器中于剩余的10％水中将甘露醇和Sucralose混合在一起。然后将多汁加到所得的混合物并溶解。
F)将步骤D)和E)的混合物加到水合聚合物凝胶，并均一地混合得到最终的聚合物凝胶混合物。将该最终的聚合物凝胶混合物浇注在模具上，并在室温下浇铸形成期望厚度的薄膜。将该可消耗薄膜在温热空气下干燥，并切成期望的尺寸(例如由剂量和口感来确定)。
表9
  材料   mg/剂*   ％w/w*干燥薄膜   ％w/w实际批量   g/批量
  右美沙芬(光谱)   10.9900   18.3460   5.5038   27.5189
  果胶USP   0.5250   0.8764   0.2629   1.3146
  材料   mg/剂*   ％w/w*干燥薄膜   ％w/w实际批量   g/批量
  胭脂红   0.1900   0.3172   0.0952   0.4758
  黄原胶   0.1154   0.1926   0.0578   0.2888
  刺槐豆胶   0.1352   0.2256   0.0677   0.3384
  角叉菜胶   0.5792   0.9668   0.2900   1.4502
  支链淀粉   30.8879   51.5621   15.4686   77.3431
  纯化水   -   -   70   350.0000
  薄荷醇   2.5740   4.2969   1.2891   6.4453
  薄荷香料   0.8000   1.3355   0.4006   2.0032
  樱桃香料(Givudan)   0.8000   1.3355   0.4006   2.0032
  酸樱桃(IFF)   2.2350   3.7310   1.1193   5.5964
  Warm Sensation(Mane)   0.8000   1.3355   0.4006   2.0032
  人造掩味剂(Robertet)   0.8000   1.3355   0.4006   2.0032
  多汁(IFF)   0.2579   0.4305   0.1292   0.6458
  聚山梨酸酯80NF   0.4504   0.7519   0.2256   1.1278
  Atmos 300   0.4504   0.7519   0.2256   1.1278
  甘油   2.0400   3.4054   1.0216   5.1082
  三氯蔗糖   2.7000   4.5072   1.3522   6.7608
  甘露醇USP   2.5740   4.2969   1.2891   6.4453
  总量   59.9042   100.0000   100.0000   500.0000
  *假定所有的水蒸发
实施例10
根据实施例7的方法，将表10所列的成分合并以提供一种可消耗薄膜。
表10
  材料   mg/剂*   ％w/w*干燥薄膜   ％w/w实际批量   g/批量
  右美沙芬(研磨)   10.9900   26.6157   9.2695   18.5390
  Amberlite IRP69   2.4000   5.8123   2.0243   4.04486
  果胶USP   0.2698   0.6534   0.2276   0.4551
  胭脂红   0.1464   0.3546   0.1235   0.2470
  黄原胶   0.0594   0.1439   0.0501   0.1002
  刺槐豆胶   0.0694   0.1681   0.0585   0.1171
  角叉菜胶   0.2975   0.7205   0.2509   0.5019
  支链淀粉   15.8694   38.4327   13.3850   26.7701
  纯化水   -   -   65.1728   130.3456
  薄荷醇   2.5740   6.2337   2.1710   4.3421
  薄荷香   0.1987   0.4812   0.1676   0.3352
  樱桃香料(Givudan)   0.1987   0.4812   0.1676   0.3352
  酸樱桃(IFF)   1.7225   4.1716   1.4528   2.9057
  Warm Sensation(Mane)   0.4252   1.0298   0.3586   0.7173
  人造掩味剂(Robertet)   0.3190   0.7726   0.2691   0.5381
  多汁(IFF)   0.1987   0.4812   0.1676   0.3352
  聚山梨酸酯80NF   0.3470   0.8404   0.2927   0.5854
  Atmos  300   0.3470   0.8404   0.2927   0.5854
  甘油   1.4877   3.6029   1.2548   2.5096
  甘露醇USP   1.9837   4.8041   1.6732   3.3463
  三氯蔗糖   1.3873   3.3598   1.1701   2.3402
  总量   41.2914   100.0000   100.0000   200.0000
  材料   mg/剂*   ％w/w*干燥薄膜   ％w/w实际批量   g/批量
  *假定所有的水蒸发
实施例11
根据以下方法将表11所列的成分合并以提供本发明的可消耗薄膜：
A)75℃下将右美沙芬HBr混合并溶于90％水得到水相。将Amberlite树脂加到水相，并在70℃-80℃下混合大约4小时。将水相冷却至大约50℃，并加入适量的水以替代由于蒸发导致的损失。
B)将果胶分散在甘油中，将所得的混合物非常缓慢地加到水相，并以高混合速度混合。
C)在单独的容器中将成膜成分、黄原胶、刺槐豆胶、角叉菜胶和支链淀粉混合在一起以形成一种成膜混合物。将该成膜混合物缓慢加到水相并快速混合。将所得的混合物在低速下混合过夜。
D)在单独的容器中，将氯化钠、甘露醇和Sucralose加到剩余的10％水中。然后将多汁加到混合物以得到一种浆液。将该浆液加到步骤C)所得的混合物中。
E)在单独的容器中将香料、薄荷醇和表面活性剂合并并混合至溶解。
F)将步骤D)和E)的混合物均一地混合得到最终的聚合物凝胶混合物。将该最终的聚合物凝胶混合物浇注在模具上，并在室温下浇铸形成期望厚度的薄膜。将该可消耗薄膜在温热空气下干燥，并切成期望的尺寸(例如由剂量和口感来确定)。
表11
  材料   mg/剂*   ％w/w*干燥薄膜   ％w/w实际批量   g/批量
  右美沙芬HBr   15.0000   22.4137   7.1724   35.8619
  碳酸氢钠   4.0000   5.9770   1.9126   9.5632
  Amberlite IRP 69   8.0000   11.9540   3.8253   19.1264
  果胶USP   0.3500   0.5230   0.1674   0.8368
  Yellow#6   0.0200   0.0299   0.0096   0.0478
  黄原胶   0.0500   0.0747   0.0239   0.1195
  刺槐豆胶   0.1000   0.1494   0.0478   0.2391
  角叉菜胶   0.5000   0.7471   0.2391   1.1954
  支链淀粉   23.3333   34.8657   11.1570   55.7852
  材料   mg/剂*   ％w/w*干燥薄膜   ％w/w实际批量   g/批量
  纯化水   -   -   68.0000   340.0000
  薄荷醇   2.5700   3.8402   1.2289   6.1443
  红橘油   0.5000   0.7471   0.2391   1.1954
  天然和人造橙   0.3000   0.4483   0.1434   0.7172
  人造柠檬油   0.3000   0.4483   0.1434   0.7172
  Warm Sensation(Mane)   0.4000   0.5977   0.1913   0.9563
  人造掩味剂(Robertet)   0.50000   0.7471   0.2391   1.1954
  多汁(IFF)   0.3000   0.4483   0.1434   0.7172
  聚山梨酸酯80NF   0.6000   0.8965   0.2869   1.4345
  Atmos 300   0.6000   0.8965   0.2869   1.4345
  甘油   2.0000   2.9885   0.9563   4.7816
  三氯蔗糖   2.7000   4.0345   1.2910   6.4552
  甘露醇USP   3.8000   5.6781   1.8170   9.0850
  氯化钠   1.0000   1.4942   0.4782   2.3908
  总量   66.9233   100.0000   100.0000   500.0000
  *假定所有的水蒸发
实施例12
根据以下方法将表12所列的成分合并以提供本发明的可消耗薄膜：
A)75℃下将右美沙芬HBr混合并溶于90％水得到水相。加入碳酸氢钠并混合大约1小时。将Amberlite IRP69加到水相，并在70℃-80℃下混合大约2小时。将所得的混合物冷却至大约50℃，并加入适量的水以替代由于蒸发导致的损失。然后将染料加到水相并充分混合。
B)在单独的容器中缓慢加入成膜成分、黄原胶、刺槐豆胶、角叉菜胶和支链淀粉并快速混合在一起以形成一种成膜混合物。将该混合物在低速下混合过夜。将分散在甘油中的果胶缓慢加到成膜混合物并以高混合速度混合。
C)将该成膜混合物缓慢加到A)的水相，然后以低混合率混合过夜以得到一种水合聚合物凝胶。
D)在另一个容器中，加入剩余的10％水以溶解甘露醇和Sucralose。然后加入多汁并混合至溶解。将所得的混合物加到水合聚合物凝胶中。
E)在单独的容器中将香料、薄荷醇和表面活性剂合并并混合至溶解以得到一种有机相。
F)将步骤D)和E)的混合物加在一起，并均一地混合得到最终的聚合物凝胶混合物。将该最终的聚合物凝胶混合物浇注在模具上，并在室温下浇铸形成期望厚度的薄膜。将该可消耗薄膜在温热空气下干燥，并切成期望的尺寸(例如由剂量和口感来确定)。
表12
  材料   mg/剂*   ％w/w*干燥薄膜   ％w/w实际批量   g/批量
  右美沙芬HBr   15.0000   27.3219   9.6903   484.5135
  Amberlite IRP 69   8.0000   14.5717   5.1681   258.4072
  果胶USP   0.2698   0.4914   0.1743   8.7148
  无水碳酸氢钠   4.0000   7.2858   2.5841   129.2036
  胭脂红   0.1464   0.2667   0.0946   4.7289
  黄原胶   0.0594   0.1082   0.0384   1.91187
  刺槐豆胶   0.0694   0.1264   0.0448   2.2417
  角叉菜胶   0.2975   0.5419   0.1922   9.6095
  支链淀粉   15.8690   28.9047   10.2517   512.5830
  纯化水   -   -   64.5329   3226.6450
  薄荷醇   2.5740   4.6884   1.6629   83.1425
  薄荷香料   0.1987   0.3619   0.1284   6.4182
  樱桃香料(Givudan)   0.1987   0.3619   0.1284   6.4182
  樱桃香料混合物(IFF)   1.7225   3.1375   1.1128   55.6383
  Warm Sensation(Mane)   0.4252   0.7745   0.2747   13.7343
  人造掩味剂(Robertet)   0.3190   0.5810   0.2061   10.3040
  多汁(IFF)   0.1987   0.3619   0.1284   6.4182
  材料   mg/剂*   ％w/w*干燥薄膜   ％w/w实际批量   g/批量
  聚山梨酸酯80NF   0.3470   0.6320   0.2242   11.2084
  Atmos 300   0.3470   0.6320   0.2242   11.2084
  甘油   1.4877   2.7100   0.9611   48.0573
  甘露醇USP   1.9837   3.6132   1.2815   64.0753
  三氯蔗糖   1.3873   2.5269   0.8962   44.8110
  总量   54.9011   100.0000   100.0000   50000.0000
  *假定所有的水蒸发
实施例13
根据实施例11的方法，除了在步骤E)还将水杨酸甲酯、桉油精和百里酚加到香料、薄荷醇和表面活性剂中，将表13所列的成分合并以提供一种可消耗薄膜。
表13
  材料   mg/剂*   ％w/w*干燥薄膜   ％w/w实际批量   g/批量
  右美沙芬HBr   15.0000   22.1962   7.1028   35.5139
  碳酸氢钠   4.0000   5.9190   1.8941   9.4704
  Amberlite IRP 69   8.0000   11.8380   3.7882   18.9408
  果胶USP   0.3500   0.5179   0.1657   0.8287
  Yellow#6   0.0200   0.0296   0.0095   0.0474
  黄原胶   0.0500   0.0740   0.0237   0.1184
  刺槐豆胶   0.1000   0.1480   0.0474   0.2368
  角叉菜胶   0.5000   0.7399   0.2368   1.1838
  支链淀粉   23.3333   34.5274   11.0488   55.2438
  纯化水   -   -   68.0000   340.0000
  百里酚   0.1698   0.2513   0.0804   0.4020
  材料   mg/剂*   ％w/w*干燥薄膜   ％w/w实际批量   g/批量
  水杨酸甲酯   0.2430   0.3596   0.1151   0.5753
  桉油精   0.2430   0.3596   0.1151   0.5753
  薄荷醇   2.5700   3.8030   1.2169   6.0847
  红橘油   0.5000   0.7399   0.2368   1.1838
  天然和人造橙   0.3000   0.4439   0.1421   0.7103
  人造柠檬油   0.3000   0.4439   0.1421   0.7103
  Warm Sensation(Mane)   0.4000   0.5919   0.1894   0.9470
  人造掩味剂(Robertet)   0.50000   0.7399   0.2368   1.1838
  多汁(IFF)   0.3000   0.4439   0.1421   0.7103
  聚山梨酸酯80NF   0.6000   0.8878   0.2841   1.4206
  Atmos  300   0.6000   0.8878   0.2841   1.4206
  甘油   2.0000   2.9595   0.9470   4.7352
  三氯蔗糖   2.7000   3.9953   1.2785   6.3925
  甘露醇USP   3.8000   5.6230   1.7994   8.9969
  氯化钠   1.0000   1.4797   0.4735   2.3676
  总量   67.5791   100.0000   100.0000   500.0000
  *假定所有的水蒸发
实施例14
根据以下方法将表14所列的成分合并以提供本发明的可消耗薄膜：
A)75℃下将右美沙芬HBr混合并溶于90％水得到水相。将氢氧化钠加到水相并充分混合。然后将Amberlite树脂加到水相，并在70℃-80℃下混合大约4小时。将水相冷却至大约50℃，并加入适量的水以代替由于蒸发导致的损失。
B)将果胶非常缓慢地加到水相，同时以高混合速度混合。
C)在单独的容器中将成膜成分、黄原胶、刺槐豆胶、角叉菜胶和支链淀粉混合在一起以形成一种成膜混合物。将该成膜混合物缓慢加到水相同时快速混合。将所得的混合物低速混合过夜。
D)在单独的容器中，将甘露醇和Sucralose加到剩余10％水中。然后将多汁加到混合物以产生一种浆液。将该浆液加到步骤C)所得的混合物。
E)在单独的容器中将香料、薄荷醇和表面活性剂合并并混合直至溶解。
F)将步骤D)和E)的混合物均一地混合得到最终的聚合物凝胶混合物。将该最终的聚合物凝胶混合物浇注在模具上，并在室温下浇铸形成期望厚度的薄膜。将该可消耗薄膜在温热空气下干燥，并切成期望的尺寸(例如由剂量和口感来确定)。
表14
  材料   mg/剂*   ％w/w*干燥薄膜   ％w/w实际批量   g/批量
  右美沙芬HBr   15.0000   23.1042   7.3933   36.9667
  氢氧化钠1N溶液   5.0000   7.7014   2.4644   12.3222
  Amberlite IRP 69   8.0000   12.3222   3.9431   19.7156
  果胶USP   0.3500   0.5391   0.1725   0.8626
  Yellow#6   0.0200   0.0308   0.0099   0.0493
  黄原胶   0.0500   0.0770   0.0246   0.1232
  刺槐豆胶   0.1000   0.1540   0.0493   0.2464
  角叉菜胶   0.5000   0.7701   0.2464   1.2322
  支链淀粉   23.3333   35.9398   11.5007   57.5037
  纯化水   -   -   68.0000   340.0000
  薄荷醇   2.5700   3.9585   1.2667   6.3336
  红橘油   0.5000   0.7701   0.2464   1.2322
  天然和人造橙   0.3000   0.4621   0.1479   0.7393
  人造柠檬油   0.3000   0.4621   0.1479   0.7393
  Warm Sensation(Mane)   0.4000   0.6161   0.1972   0.9858
  人造掩味剂(Robertet)   0.5000   0.7701   0.2464   1.2322
  多汁(IFF)   0.3000   0.4621   0.1479   0.7393
  材料   mg/剂*   ％w/w*干燥薄膜   ％w/w实际批量   g/批量
  聚山梨酸酯80NF   0.6000   0.9242   0.2957   1.4787
  Atmos 300   0.6000   0.9242   0.2957   1.4787
  三氯蔗糖   2.7000   4.1588   1.3308   6.6540
  甘露醇USP   3.8000   5.8531   1.8730   9.3649
  总量   64.9233   100.0000   100.0000   500.0000
  *假定所有的水蒸发
实施例15
根据实施例14的方法，除了在步骤E)还将水杨酸甲酯、桉油精和百里酚加到香料、薄荷醇和表面活性剂中，将表15所列的成分合并以提供一种可消耗薄膜。
表15
  材料   mg/剂*   ％w/w*干燥薄膜   ％w/w实际批量   g/批量
  右美沙芬HBr   15.0000   22.7690   7.2861   36.4304
  氢氧化钠1N溶液   4.0000   7.5897   2.4287   12.1435
  Amberlite IRP 69   8.0000   12.1435   3.8859   19.4295
  果胶USP   0.3500   0.5313   0.1700   0.8500
  Yellow#6   0.0200   0.0304   0.0097   0.0486
  黄原胶   0.0500   0.0759   0.0243   0.1214
  刺槐豆胶   0.1000   0.1518   0.0486   0.2429
  角叉菜胶   0.5000   0.7590   0.2429   1.2143
  支链淀粉   23.3333   35.4184   11.3339   56.6694
  纯化水   -   -   68.0000   340.0000
  百里酚   0.1698   0.2577   0.0825   0.4124
  水杨酸甲酯   0.2430   0.3689   0.1180   0.5902
  材料   mg/剂*   ％w/w*干燥薄膜   ％w/w实际批量   g/批量
  桉油精   0.2430   0.3689   0.1180   0.5902
  薄荷醇   2.8700   4.3565   1.3941   6.9703
  红橘油   0.5000   0.7590   0.2429   1.2143
  天然和人造橙   0.3000   0.4554   0.1457   0.7286
  人造柠檬油   0.3000   0.4554   0.1457   0.7286
  Warm Sensation(Mane)   0.4000   0.6072   0.1943   0.9715
  人造掩味剂(Robertet)   0.50000   0.7590   0.2429   1.2143
  多汁(IFF)   0.3000   0.4554   0.1457   0.7286
  聚山梨酸酯80NF   0.6000   0.9108   0.2914   1.4572
  Atmos  300   0.6000   0.9108   0.2914   1.4572
  三氯蔗糖   2.7000   4.0984   1.3115   6.5575
  甘露醇USP   3.8000   5.7681   1.8458   9.2290
  总量   67.5791   100.0000   100.0000   500.0000
  *假定所有的水蒸发
前述的讨论仅仅公开和描述本发明的例示性实施方案。本领域技术人员将由这些讨论和所附的权利要求容易地认识到在不背离以下权利要求定义的本发明的构思和范围的情况下可以作许多改变、修改和变更。

Claims (2)

1.适于粘着并且溶解在使用者口腔中的可消耗薄膜，该薄膜包含支链淀粉、右美沙芬氢溴酸盐和作为粘膜包覆剂的果胶，所述粘膜包覆剂的浓度为0.1wt％至2wt％，以保持右美沙芬氢溴酸盐与口腔和咽喉的受影响区域之间的接触。
2.权利要求1的可消耗薄膜，其中该右美沙芬氢溴酸盐以2.5mg至20mg的量存在。
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