CN109310646A - 增强递送的肾上腺素组合物 - Google Patents
增强递送的肾上腺素组合物 Download PDFInfo
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- CN109310646A CN109310646A CN201780037587.5A CN201780037587A CN109310646A CN 109310646 A CN109310646 A CN 109310646A CN 201780037587 A CN201780037587 A CN 201780037587A CN 109310646 A CN109310646 A CN 109310646A
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0053—Mouth and digestive tract, i.e. intraoral and peroral administration
- A61K9/006—Oral mucosa, e.g. mucoadhesive forms, sublingual droplets; Buccal patches or films; Buccal sprays
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/70—Web, sheet or filament bases ; Films; Fibres of the matrix type containing drug
- A61K9/7007—Drug-containing films, membranes or sheets
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/02—Drugs for disorders of the nervous system for peripheral neuropathies
Abstract
本发明描述了具有增强的活性成分渗透性质的药物组合物。
Description
优先权的要求
本申请根据35 U.S.C.§119(e)要求2016年5月5日提交的美国专利申请序列号62/331,996的优先权,其以其整体通过引用并入本发明。
技术领域
本发明涉及药物组合物。
背景技术
活性成分,例如药物或药品,以慎重的方式递送给患者。使用膜经皮或经粘膜递送药物或药品可需要药物或药品以有效和有效力的方式渗透或以其他方式穿过生物膜。
发明内容
通常,药物组合物可包含聚合物基质、在聚合物基质中的肾上腺素、和肾上腺素能受体相互作用剂。在一些实施方案中,所述药物组合物可进一步包含渗透增强剂。在一些实施方案中,肾上腺素能受体相互作用剂可为肾上腺素能受体阻断剂。在一些实施方案中,肾上腺素能受体相互作用剂也可为类黄酮,或与类黄酮组合使用。
在一些实施方案中,所述肾上腺素能受体相互作用剂可为类萜、萜或C3-C22醇或酸。肾上腺素能受体相互作用剂可为倍半萜烯(sesquiterpene)。在一些实施方案中,所述肾上腺素能受体相互作用剂可包括法尼醇、亚油酸、花生四烯酸、二十二碳六烯酸(docosahexanoic acid)、二十碳五烯酸、或二十二碳五烯酸(docosapentanoic acid),或其组合。
在一些实施方案中,所述药物组合物可为进一步包含聚合物基质的膜,该药物活性成分包含在聚合物基质中。
在一些实施方案中,所述肾上腺素能受体相互作用剂可为植物提取物。
在一些实施方案中,所述渗透增强剂可为植物提取物(phytoextract)。
在一些实施方案中,所述渗透增强剂可包括类苯丙烷(phenylpropanoid)。
在一些实施方案中,所述药物组合物可包含真菌提取物。
在一些实施方案中,所述药物组合物可包含饱和或不饱和醇。
在一些实施方案中,所述醇可为苄醇。
在一些情况下,类黄酮、植物提取物、类苯丙烷、丁子香酚或真菌提取物可用作增溶剂。
在一些实施方案中,所述类苯丙烷可为丁子香酚。在其它实施方案中,所述类苯丙烷可为乙酸丁子香酚酯。在一些实施方案中,所述类苯丙烷可为肉桂酸。在其它实施方案中,所述类苯丙烷可为肉桂酸酯。在其它实施方案中,类苯丙烷可为肉桂醛。
在其它实施方案中,所述类苯丙烷可为氢化肉桂酸。在一些实施方案中,所述类苯丙烷可为佳味酚(chavicol)。在其它实施方案中,所述类苯丙烷可为黄樟素(safrole)。
在一些实施方案中,所述植物提取物可为丁香植物的精油提取物。在其它实例中,所述植物提取物可为丁香植物叶子的精油提取物。所述植物提取物可为丁香植物花芽的精油提取物。在其它实施方案中,所述植物提取物可为丁香植物茎的精油提取物。
在一些实施方案中,所述植物提取物可为合成的。在一些实施方案中,所述植物提取物可包含20-95%丁子香酚,包含40-95%丁子香酚,和包含60-95%丁子香酚。在一些实施方案中,所述植物提取物可包含80-95%丁子香酚。
在一些实施方案中,所述聚合物基质可包含聚合物。在一些实施方案中,所述聚合物可包括水溶性聚合物。
在一些实施方案中,所述聚合物可为聚氧化乙烯。
在一些实施方案中,所述聚合物可为纤维素聚合物。在一些实施方案中,所述纤维素聚合物可为羟丙基甲基纤维素、羟基乙基纤维素、羟基乙基甲基纤维素、羟丙基纤维素、甲基纤维素、羧基甲基纤维素和/或羧基甲基纤维素钠。
在一些实施方案中,所述聚合物可包括羟丙基甲基纤维素。
在一些实施方案中,所述聚合物可包括聚氧化乙烯和/或羟丙基甲基纤维素。
在一些实施方案中,所述聚合物可包括聚氧化乙烯和/或聚乙烯吡咯烷酮。
在一些实施方案中,所述聚合物基质可包括聚氧化乙烯和/或多糖。
在一些实施方案中,所述聚合物基质可包括聚氧化乙烯、羟丙基甲基纤维素和/或多糖。
在一些实施方案中,所述聚合物基质可包括聚氧化乙烯、纤维素聚合物、多糖和/或聚乙烯吡咯烷酮。
在一些实施方案中,所述聚合物基质可包含至少一种选自以下的聚合物:普鲁兰多糖、聚乙烯吡咯烷酮、聚乙烯醇、藻酸钠、聚乙二醇、黄原胶、黄蓍胶、瓜尔胶、阿拉伯树胶(acacia gum)、阿拉伯胶(arabic gum)、聚丙烯酸、甲基丙烯酸甲酯共聚物、羧基乙烯基共聚物、淀粉、明胶、环氧乙烷、环氧丙烷共聚物、胶原、白蛋白、聚氨基酸、聚磷腈、多糖、甲壳质、壳聚糖及其衍生物。
在一些实施方案中,所述药物组合物可进一步包含稳定剂。稳定剂可以包括抗氧化剂(它可以防止材料的不必要的氧化)、螯合剂(螯合剂可以形成螯合物并灭活痕量的金属离子,否则它们可以作为催化剂)、乳化剂和表面活性剂(其可以稳定乳液)、紫外线稳定剂(其可以保护材料免受紫外线辐射的有害影响)、紫外线吸收剂、吸收紫外线辐射和防止其渗透组合物的化学物质、淬灭剂(它可以以热量散发辐射能量而不是让它破坏化学键)、或清除剂(其可以消除紫外线辐射形成的自由基)。
在另一个方面,所述药物组合物具有合适的无毒非离子烷基糖苷与粘膜递送增强剂的组合,该烷基糖苷具有疏水性烷基,所述疏水性烷基通过键与亲水性糖连接,所述粘膜递送增强剂选自:(a)聚集抑制剂;(b)电荷改性剂;(c)pH控制剂;(d)降解酶抑制剂;(e)粘液溶解或粘液清除剂;(f)纤毛稳定剂(ciliostatic agent);(g)膜渗透增强剂,其选自:(i)表面活性剂;(ii)胆汁盐;(ii)磷脂添加剂、混合胶束、脂质体或载体;(iii)醇;(iv)烯胺;(v)一氧化氮供体化合物;(vi)长链两亲性分子;(vii)小的疏水渗透增强剂;(viii)钠或水杨酸衍生物;(ix)乙酰乙酸的甘油酯;(x)环糊精或β-环糊精衍生物;(xi)中链脂肪酸;(xii)螯合剂;(xiii)氨基酸或其盐;(xiv)N-乙酰氨基酸或其盐;(xv)降解选定的膜组分的酶;(ix)脂肪酸合成抑制剂;(x)胆固醇合成抑制剂;和(xi)(i)-(x)中所述的膜渗透增强剂的任何组合;(h)上皮连接生理学的调节剂;(i)血管扩张剂;(j)选择性运输增强剂;(k)稳定递送工具、载体、粘膜粘着剂、支持体或复合物形成剂,由此化合物被有效地组合、联合、包含、包封、或结合,导致该化合物的稳定性,以增强粘膜递送,其中用跨粘膜递送增强剂配制化合物提供了受试者血浆内增加的化合物生物利用率。
通常,制备药物组合物的方法可包括将肾上腺素能受体相互作用剂与药物活性成分(包括肾上腺素)组合,和形成包含该肾上腺素能受体相互作用剂和药物活性成分的药物组合物。
通常,药物组合物可从装置分配。装置可包括容纳一定量的药物组合物的外壳,该药物组合物包含聚合物基质;在聚合物基质中的药物活性成分(包括肾上腺素);和肾上腺素能受体相互作用剂,且该装置包含分配预定量(例如预定剂量)的药物组合物的开口。该装置也可分配包含渗透增强剂的药物组合物,该渗透增强剂包括类苯丙烷和/或植物提取物。
根据以下描述、附图和权利要求,其他方面、实施方案和特征将是显而易见的。
附图简述
参考图1A,Franz扩散池100包括供体化合物101、供体室102、膜103、取样口104、接收室105、搅拌棒106和加热器/循环器107。
参考图1B,药物组合物是包含聚合物基质200的膜100,药物活性成分300包含在聚合物基质中。该膜可包括渗透增强剂400。
参考图2A和2B,该图显示了活性物质从组合物中的渗透。
参考图2A,该图显示了渗透的活性物质的平均量相对时间的关系,其中具有8.00mg/mL肾上腺素酒石酸氢盐和溶解的4.4mg/mL肾上腺素碱。
参考图2B,该图显示平均通量与时间的关系,其中具有8.00mg/mL肾上腺素酒石酸氢盐和溶解的4.4mg/mL肾上腺素碱。
参考图3,该图显示了肾上腺素酒石酸氢盐的离体渗透作为浓度的函数。参考图4,该图显示了肾上腺素酒石酸氢盐的渗透作为溶液pH的函数。参考图5,该图显示了增强剂对肾上腺素渗透的影响,表示为渗透量随时间的函数。
参考图6A和6B,这些图显示了肾上腺素在聚合物平台上的释放(6A)和增强剂对其释放的影响(6B),表示为渗透量(以μg计)与时间的关系。参考图7,该图显示了雄性Yucatan小型猪的药代动力学模型。该研究比较了0.3毫克Epipen、0.12毫克肾上腺素IV和安慰剂膜。
参考图8,该图显示了无增强剂对40mg肾上腺素膜相对0.3mg Epipen的浓度分布的影响。
参考图9,该图显示增强剂A(Labrasol)对40mg肾上腺素膜相对0.3mg Epipen的浓度分布的影响。
参考图10,该图显示增强剂L(丁香油)对两片40mg肾上腺素膜(10-1-1)和(11-1-1)相对0.3mg Epipen的浓度分布的影响。
参考图11,该图显示了增强剂L(丁香油)和膜尺寸(10-1-1更薄、更大的膜,11-1-1更厚、更小的膜)对40mg肾上腺素膜相对0.3mg Epipen的浓度分布的影响。
参考图12,该图显示了增强剂L(丁香油)的恒定基质中不同剂量的肾上腺素膜相对0.3mg Epipen的浓度分布。
参考图13,该图显示了增强剂L(丁香油)的恒定基质中不同剂量的肾上腺素膜相对0.3mg Epipen的浓度分布。
参考图14,该图显示了增强剂A(Labrasol)的恒定基质中不同剂量的肾上腺素膜相对0.3mg Epipen的浓度分布。
参考图15,该图显示法尼醇和法尼醇与亚油酸的组合对40mg肾上腺素膜相对0.3mg Epipen的血浆浓度分布的影响。
参考图16,该图显示法尼醇对40mg肾上腺素膜相对0.3mg Epipen的血浆浓度分布的影响。
参考图17,该图显示法尼醇与亚油酸的组合对40mg肾上腺素膜相对0.3mg Epipen的血浆浓度分布的影响。
参考图18,该图显示法尼醇和法尼醇与亚油酸的组合对40mg肾上腺素膜相对0.3mg Epipen的血浆浓度分布的影响。
参考图19,该图显示增强剂A(Labrasol)与增强剂L(丁香油)的组合对40mg肾上腺素膜的浓度分布的影响(还示于图20),以对数显示。
参考图20,该图显示增强剂A(Labrasol)与增强剂L(丁香油)的组合对40mg肾上腺素膜的浓度分布相对从0.3mg Epipens收集的平均数据的影响。
参考图21,该图显示增强剂A(Labrasol)与增强剂L(丁香油)的组合对40mg肾上腺素膜的浓度分布的影响,以分开的动物受试者显示。
发明详述
粘膜表面,例如口腔粘膜,是将药物输送到身体的便利途径,因为它们具有高度血管化和渗透性,提供了增加的生物利用度和快速起效,因为它不通过消化系统,从而避免了首过代谢。特别地,口腔和舌下组织为药物递送提供了有利的位置,因为它们是口腔粘膜的高渗透性区域,允许药物从口腔粘膜扩散以直接进入体循环。这也提供了更多的便利性,因此增加了患者的顺应性。对于一些药物或药物活性组分,渗透增强剂可有助于克服粘膜屏障并改善渗透性。渗透增强剂可逆地调节阻挡层的渗透性,有利于药物吸收。渗透增强剂促进分子通过上皮的运输。可以通过多种参数来控制和调节吸收曲线及其速率,例如但不限于膜尺寸、药物负载、增强剂类型/负载、聚合物基质释放速率和粘膜停留时间。
可以设计药物组合物以有意和定制的方式递送药物活性组分。然而,药物活性组分在体内,特别是在受试者口中的溶解度和渗透性可以极大地变化。特定类别的渗透增强剂可以改善体内药物活性组分的摄取和生物利用度。特别地,当通过膜递送至口腔时,渗透增强剂可以改善药物活性组分通过粘膜和进入受试者血流的渗透性。渗透增强剂可改善吸收率和药物活性成分的量达:多于5%、多于10%、多于20%、多于30%、多于40%、多于50%、多于60%、多于70%、多于80%、多于90%、多于100%、多于150%、约200%或更多,或少于200%、少于150%、少于100%、少于90%、少于80%、少于70%、少于60%、少于50%、少于40%、少于30%、少于20%、少于10%、或少于5%,或这些范围的组合,取决于组合物中的其他组分。
在一些实施方案中,药物组合物具有合适的无毒非离子烷基糖苷与粘膜递送增强剂的组合,该烷基糖苷具有疏水性烷基,所述疏水性烷基通过键与亲水性糖连接,所述粘膜递送增强剂选自:(a)聚集抑制剂;(b)电荷改性剂;(c)pH控制剂;(d)降解酶抑制剂;(e)粘液溶解或粘液清除剂;(f)纤毛稳定剂;(g)膜渗透增强剂,其选自:(i)表面活性剂;(ii)胆汁盐;(ii)磷脂添加剂、混合胶束、脂质体或载体;(iii)醇;(iv)烯胺;(v)一氧化氮供体化合物;(vi)长链两亲分子;(vii)小的疏水渗透增强剂;(viii)钠或水杨酸衍生物;(ix)乙酰乙酸的甘油酯;(x)环糊精或β-环糊精衍生物;(xi)中链脂肪酸;(xii)螯合剂;(xiii)氨基酸或其盐;(xiv)N-乙酰氨基酸或其盐;(xv)对选定的膜组分降解的酶;(ix)脂肪酸合成抑制剂;(x)胆固醇合成抑制剂;和(xi)(i)-(x)中所述的膜渗透增强剂的任何组合;(h)上皮连接生理学的调节剂;(i)血管扩张剂;(j)选择性运输增强剂;(k)稳定递送工具、载体、粘膜粘着剂、支持体或复合物形成剂,由此化合物被有效地组合、联合、包含、包封、或结合,导致该化合物的稳定性,以增强粘膜递送,其中用跨粘膜递送增强剂配制化合物提供了受试者血浆内增加的化合物生物利用率。渗透增强剂已描述于J.Nicolazzo,等人,J.ofControlled Disease,105(2005)1-15,其通过引用并入本发明。
关于口腔粘膜是将治疗剂递送到体循环中的有吸引力的部位是有很多原因的。由于血液从颊上皮直接排入颈内静脉,可以避免肝脏和肠道中的首过代谢。当口服给药时,首过效应可以是一些化合物生物利用度差的主要原因。另外,口腔内的粘膜易于接近,这确保剂型可以应用于所需部位并且在紧急情况下可以容易地移除。然而,与皮肤一样,颊粘膜充当了外源性物质(xenobiotic)吸收的屏障,这可阻碍化合物穿过该组织。因此,鉴定安全有效的渗透增强剂已成为寻求改善口腔粘膜药物递送的主要目标。
化学渗透增强剂是控制共同施用药物通过生物膜的渗透速率的物质。虽然广泛的研究集中在更好地理解渗透增强剂如何改变肠道和透皮渗透性,但是对于口腔和舌下渗透增强所涉及的机制知之甚少。
颊粘膜为脸颊的内衬以及牙龈和上唇和下唇之间的区域,并且其平均表面积为100cm2。颊粘膜的表面由分层的鳞状上皮组成,其通过起伏的基底膜(厚度约1-2μm的连续细胞外物质层)与下面的结缔组织(固有层和粘膜下层)分离。这种分层的鳞状上皮由分化的细胞层组成,当它们从基底区域移动到细胞脱落的表面区域时,细胞层的大小、形状和含量发生变化。大约有40-50个细胞层,导致颊粘膜厚度为500-600μm。
在结构上,舌下粘膜与颊粘膜相当,但该上皮的厚度为100-200μm。该膜也是非角质化的,并且相对较薄,已被证明比颊粘膜更具渗透性。与颊粘膜相比,流向舌下粘膜的血流较慢,并且为约1.0ml/min-1/cm-2。
颊粘膜的渗透性大于皮肤的渗透性,但小于肠粘膜的渗透性。渗透性的差异是每种组织之间结构差异的结果。与角质化的皮肤上皮细胞相比,在颊粘膜的细胞间隙中不存在有组织的脂质层,这导致外源性化合物的更大渗透性;而增加的厚度和缺乏紧密连接导致颊粘膜比肠组织渗透性差。
颊粘膜的主要屏障特性归因于颊上皮的上三分之一至四分之一。研究人员已经了解到,在表面上皮之外,非角化口腔粘膜的渗透屏障也可归因于从膜包衣颗粒挤出到上皮细胞间隙中的内容物。
口腔的非角化区域的细胞间脂质具有比表皮、腭和牙龈的脂质更极性的性质,并且脂质的化学性质的这种差异可造成在这些组织之间观察到的渗透性的差异。因此,不仅角质化上皮的角质层中较大程度的细胞间脂质堆积会产生更有效的屏障,该屏障内存在的脂质的化学性质也会产生更有效的屏障。
口腔粘膜中亲水和亲脂区域的存在使得研究人员假定通过颊粘膜-细胞旁(细胞之间)和跨细胞(穿过细胞)存在两种药物转运途径。
由于通过颊粘膜的药物递送受到上皮的屏障性质和可用于吸收的区域的限制,因此需要各种增强策略以将治疗相关量的药物递送至体循环。可以采用多种方法,包括使用化学渗透增强剂、前药和物理方法来克服颊粘膜的屏障性质。
化学渗透增强剂或吸收促进剂是添加到药物制剂中的物质,以增加共同施用药物的膜渗透或吸收率,而不损害膜和/或引起毒性。已经有许多研究调查了化学渗透促进剂对跨越皮肤、鼻粘膜和肠道的化合物递送的影响。近年来,这些药剂对颊粘膜渗透性的影响越来越受到关注。由于颊粘膜的渗透性被认为是被动扩散过程,因此根据Fick的第一扩散定律,稳态通量(Jss)应随着供体室浓度(CD)的增加而增加。
表面活性剂和胆汁盐已经显示出在体外和体内增强各种化合物穿过颊粘膜的渗透性。从这些研究中获得的数据强烈表明渗透性的增强是由于表面活性剂对粘膜细胞间脂质的影响。
已经显示脂肪酸增强了许多药物通过皮肤的渗透,并且已经通过差示扫描量热法和傅里叶变换红外光谱显示这与细胞间脂质的流动性的增加有关。
此外,乙醇预处理已显示可增强氚化水和白蛋白穿过舌腹侧粘膜的渗透性,并提高咖啡因穿过猪颊粘膜的渗透性。还有一些关于对化合物通过口腔粘膜的渗透性的增强效果的报道。此外,壳聚糖(一种生物相容的和可生物降解的聚合物)已经显示出增强药物通过各种组织(包括肠和鼻粘膜)的递送。
口服透粘膜药物递送(OTDD)是通过口腔粘膜施用药物活性剂以实现全身效应。OTDD的渗透途径和预测模型,描述于例如M.Sattar,Oral transmucosal drug delivery–Current status and future prospects,Int’l.Journal of Pharmaceutics,47(2014)498-506,其通过引用并入本发明。OTDD继续吸引学术和工业科学家的注意。尽管与皮肤和鼻腔递送途径相比,对口腔中渗透途径的表征有限,但是由于我们对离子化分子渗透颊上皮的理解程度的最新进展,以及用于研究口腔的新分析技术的出现,以及预测颊和舌下渗透的计算机模型的进展,前景令人鼓舞。
为了通过颊粘膜递送更广泛类别的药物,应采用降低该组织屏障潜能的可逆方法。这一必要条件促进了渗透促进剂的研究,该研究将安全地改变颊粘膜的渗透性限制。已经表明,通过使用各种类型的透粘膜和透皮渗透增强剂,例如胆汁盐、表面活性剂、脂肪酸及其衍生物、螯合剂、环糊精和壳聚糖,可以改善口腔渗透。在用于药物渗透增强的这些化学品中,胆汁盐是最常见的。
胆汁盐对化合物口腔渗透的增强作用的体外研究在Sevda Senel,Drugpermeation enhancement via buccal route:possibilities and limitations,Journalof Controlled Release 72(2001)133–144中讨论,其通过引用并入本发明。该文章还讨论了关于二羟胆汁盐、甘氨脱氧胆酸钠(SGDC)和牛磺脱氧胆酸钠(TDC)和三羟基胆汁盐、甘氨胆酸钠(GC)和牛磺胆酸钠(TC)的颊上皮渗透性在100mM浓度的影响的最近研究,包括与组织学效应相关的渗透性变化。异硫氰酸荧光素(FITC)、硫酸吗啡各自被用作模型化合物。
壳聚糖还显示在动物模型和人类志愿者中促进小极性分子和肽/蛋白质药物通过鼻粘膜的吸收。其他研究已表明对化合物穿过肠粘膜和培养的Caco-2细胞的渗透增强作用。
渗透增强剂可为植物提取物。植物提取物可以是精油或包含通过蒸馏植物材料提取的精油的组合物。在一些情况下,植物提取物可包括从植物材料中提取的化合物的合成类似物(即,通过有机合成制备的化合物)。植物提取物可包括类苯丙烷,例如苯丙氨酸、丁子香酚、乙酸丁子香酚酯、肉桂酸、肉桂酸酯、肉桂醛、氢化肉桂酸、佳味酚或黄樟脑,或其组合。植物提取物可为丁香植物的精油提取物,例如,来自丁香植物的叶、茎或花芽。丁香植物可以是丁香(Syzygium aromaticum)。提取物可包含20-95%的丁子香酚,包含40-95%丁子香酚,包含60-95%丁子香酚,和例如80-95%丁子香酚。提取物还可包含5%至15%的乙酸丁子香酚酯。提取物还可以包括丁香烯。提取物还可以包含高达2.1%的α-律草烯(humulen)。在丁香精油中包含的较低浓度的其他挥发性化合物可以是β-蒎烯、柠檬烯、法尼醇、苯甲醛、2-庚酮和己酸乙酯。可以向组合物中加入其他渗透增强剂以改善药物的吸收。合适的渗透增强剂包括天然或合成的胆汁盐,例如夫西地酸钠;甘氨胆酸酯或脱氧胆酸酯及其盐类;脂肪酸和衍生物,如月桂酸钠、油酸、油醇、油酸单甘油酯和棕榈酰肉毒碱;螯合剂如EDTA二钠、柠檬酸钠和十二烷基硫酸钠、氮酮(azone)、胆酸钠、5-甲氧基水杨酸钠、脱水山梨糖醇月桂酸酯、甘油单月桂酸酯、辛氧基壬基-9、月桂醇聚醚-9、聚山梨醇酯、甾醇或甘油酯,如辛酰己酰聚乙二醇甘油酯,例如,Labrasol。渗透增强剂可包括植物提取物衍生物和/或单木质醇(monolignol)。渗透增强剂也可以是真菌提取物。
已知一些植物来源的天然产物具有血管舒张作用。有关综述,请参阅McNeillJ.R.和Jurgens,T.M.,Can.J.Physiol.Pharmacol.84:803-821(2006),其通过引用并入本发明。具体地,在许多动物研究中已经报道了丁子香酚的血管舒张作用。参见,例如,Lahlou,S.,等人,J.Cardiovasc.Pharmacol.43:250-57(2004),Damiani,C.E.N.,等人,Vascular Pharmacol.40:59-66(2003),Nishijima,H.,等人,Japanese J.Pharmacol.79:327-334(1998),和Hume W.R.,J.Dent Res.62(9):1013-15(1983),其每一篇通过引用并入本发明。钙通道阻滞被认为是由植物精油或其主要成分丁子香酚诱导的血管舒张的原因。参见Interaminense L.R.L.等,Fundamental&Clin.Pharmacol.21:497-506(2007),其通过引用并入本发明。
脂肪酸可用作药物制剂或药物载体中的非活性成分。脂肪酸由于其一些功能效果和它们的生物相容性也可以用作配方成分。脂肪酸,无论是游离脂质还是复合脂质的一部分,都是主要的代谢燃料(储存和运输能量),是所有膜和基因调节剂的必需成分。关于综述,参见Rustan A.C.和Drevon,C.A.,Fatty Acids:Structures and Properties,Encyclopedia of Life Sciences(2005),其通过引用并入本发明。有两个必需脂肪酸家族在人体内代谢:ω-3和ω-6多不饱和脂肪酸(PUFA)。如果在距ω碳的第三和第四碳原子之间存在第一个双键,则它们被称为ω-3脂肪酸。如果第一个双键是在第六个和第七个碳原子之间,则它们被称为ω-6脂肪酸。PUFA通过添加碳原子和通过去饱和(氢的提取)在体内进一步代谢。亚油酸是一种ω-6脂肪酸,其代谢成γ-亚麻酸、二高-γ-亚麻酸(linolinicacid,)、花生四烯酸、肾上腺酸、二十四碳四烯酸、二十四碳五烯酸和二十二碳五烯酸。作为ω-3脂肪酸的α-亚麻酸代谢为十八碳四烯酸、二十碳四烯酸、二十碳五烯酸(EPA)、二十二碳五烯酸、二十四碳五烯酸、二十四碳六烯酸和二十二碳六烯酸(DHA)。
据报道,脂肪酸,如棕榈酸、油酸、亚油酸和二十碳五烯酸,通过涉及激活Na+K+-APT酶泵和脂肪酸的机制诱导猪冠状动脉平滑肌细胞的松弛和超极化,且顺式不饱和度的增加具有更高的效力。参见Pomposiello,S.I.等人,Hypertension 31:615-20(1998),其通过引用并入本发明。有趣的是,肺血管对花生四烯酸(亚油酸的代谢物)有反应,可以是血管收缩或血管舒张的,这取决于剂量、动物种类、花生四烯酸给药方式和肺循环的状况。例如,据报道花生四烯酸会引起环氧合酶依赖性和非依赖性肺血管舒张。参见,Feddersen,C.O.等人,J.Appl.Physiol.68(5):1799-808(1990);且参见,Spannhake,E.W.等人,J.Appl.Physiol.44:397-495(1978)和Wicks,T.C.等人,Circ.Res.38:167-71(1976),其各自通过引用并入本发明。
许多研究报道了EPA和DHA在作为可摄入形式给药后对血管反应性的作用。一些研究发现EPA-DHA或EPA单独抑制去甲肾上腺素的血管收缩作用或增加前臂微循环中乙酰胆碱的血管舒张反应。参见Chin,J.P.F,等人,Hypertension 21:22-8(1993),和Tagawa,H.等,J Cardiovasc Pharmacol 33:633-40(1999),它们各自通过引用结合到本发明中。另一项研究发现,EPA和DHA均增加全身动脉顺应性,并倾向于降低脉压和总血管阻力。参见Nestel,P.等人,AmJ.Clin.Nutr.76:326-30(2002),其通过引用并入本发明。同时,一项研究发现,DHA,但不是EPA,增强血管扩张机制,且减弱高脂血症超重男性前臂微循环中的缩窄反应。参见Mori,T.A.,等人,Circulation 102:1264-69(2000),其通过引用结合到本发明中。另一项研究发现DHA对体外分离的人冠状动脉节律性收缩的血管舒张作用。参见Wu,K.-T.等人,Chinese J.Physiol.50(4):164-70(2007),其通过引用结合到本发明中。
肾上腺素能受体(或肾上腺素受体,adrenoceptor)是一类G蛋白偶联受体,其是儿茶酚胺的靶标,尤其是去甲肾上腺素(降正肾上腺素)和肾上腺素(副肾素)。肾上腺素与α-和β-肾上腺素受体相互作用,分别引起血管收缩和血管舒张。尽管α受体对肾上腺素的敏感性较低,但当它们被激活时,它们会超越β-肾上腺素受体介导的血管舒张,因为外周α1受体比β-肾上腺素受体更多。结果是高水平的循环肾上腺素引起血管收缩。在较低水平的循环肾上腺素下,β-肾上腺素受体刺激占优势,产生血管舒张,随后降低外周血管阻力。α1-肾上腺素受体已知用于平滑肌收缩、瞳孔放大、皮肤、粘膜和腹部脏器的血管收缩以及胃肠(GI)道和膀胱的括约肌收缩。α1-肾上腺素能受体是Gq蛋白偶联受体超家族的成员。激活后,异源三聚体G蛋白Gq激活磷脂酶C(PLC)。作用机制涉及与钙通道的相互作用和改变细胞中的钙含量。有关综述,参见Smith R.S.等人,Journal of Neurophysiology 102(2):1103-14(2009),其通过引用并入本发明。许多细胞都拥有这些受体。
α1-肾上腺素能受体可以是脂肪酸的主要受体。例如,据报道,广泛用于治疗良性前列腺增生(BPH)的锯棕榈提取物(SPE)可与α1-肾上腺素能、毒蕈碱和1,4-二氢吡啶(1,4-DHP)钙通道拮抗剂受体结合。参见Abe M.等人,Biol.Pharm.Bull.32(4)646-650(2009)和Suzuki M.等人,Acta Pharmacologica Sinica 30:271-81(2009),其各自通过引用并入本发明。SPE包括多种脂肪酸,包括月桂酸、油酸、肉豆蔻酸、棕榈酸和亚油酸。月桂酸和油酸可以非竞争性地结合α1-肾上腺素能、毒蕈碱和1,4-DHP钙通道拮抗剂受体。
在一些实施方案中,渗透增强剂可为肾上腺素能受体相互作用剂。肾上腺素能受体相互作用剂是指修改和/或改变肾上腺素能受体作用的化合物或物质。例如,肾上腺素能受体相互作用剂可通过增加或降低其结合能力来预防受体的刺激。这些相互作用剂可以以短效或长效形式提供。一些短效相互作用剂可以快速起作用,但它们的效果只能持续几个小时。一些长效相互作用剂可需要更长时间才能作用,但它们的效果会持续更长时间。可以基于例如所需的递送和剂量、活性药物成分、渗透调节剂、渗透增强剂、基质和所治疗的病症中的一种或多种来选择和/或设计相互作用剂。肾上腺素能受体相互作用剂可为肾上腺素能受体阻断剂。肾上腺素能受体相互作用剂可为萜(例如植物精油中的挥发性不饱和烃,衍生自异戊二烯单元)或C3-C22醇或酸,优选C7-C18醇或酸。在一些实施方案中,所述肾上腺素能受体相互作用剂可包括法尼醇、亚油酸、花生四烯酸、二十二碳六烯酸、二十碳五烯酸、和/或二十二碳五烯酸。所述酸可为羧酸、磷酸、硫酸、异羟肟酸或其衍生物。该衍生物可为酯或酰胺。例如,肾上腺素能受体相互作用剂可为脂肪酸或脂肪醇。
C3-C22醇或酸可为具有直链C3-C22烃链,例如任选含有至少一个双键、至少一个三键、或至少一个双键和一个三键的C3-C22烃链,的醇或酸;所述烃链任选取代有C1-4烷基、C2-4烯基、C2-4炔基、C1-4烷氧基、羟基、卤素、氨基、硝基、氰基、C3-5环烷基、3-5元杂环烷基、单环芳基、5-6元杂芳基、C1-4烷基羰基氧基、C1-4烷基氧基羰基、C1-4烷基羰基或甲酰基;且进一步任选插入-O-、-N(Ra)-、-N(Ra)-C(O)-O-、-O-C(O)-N(Ra)-、-N(Ra)-C(O)-N(Rb)-、或-O-C(O)-O-。Ra和Rb各自独立为氢、烷基、烯基、炔基、烷氧基、羟基烷基、羟基或卤代烷基。
具有较高不饱和度的脂肪酸是增强药物渗透的有效候选物。不饱和脂肪酸比饱和脂肪酸具有更高的增强作用,并且随着双键数的增加,增强作用增强。参见,A.Mittal等,Status of Fatty Acids as Skin Penetration Enhancers–A Review,Current DrugDelivery,2009,6,pp.274-279,其通过引用并入本发明。双键的位置也影响脂肪酸的增强活性。源自双键位置差异的脂肪酸的物理化学性质的差异最可能决定这些化合物作为皮肤渗透增强剂的功效。随着双键的位置向亲水端移动,皮肤分布增加。还报道了在偶数位置具有双键的脂肪酸比在奇数位置具有双键的脂肪酸更快地影响角质层和真皮的结构的扰动。链中的顺式不饱和度可倾向于增加活性。
肾上腺素能受体相互作用剂可为萜。已报道了精油中萜的降压活性。参见,Menezes I.A.等人,Z.Naturforsch.65c:652-66(2010),其通过引用并入本发明。在一些实施方案中,所述渗透增强剂可为倍半萜烯。倍半萜烯为一类由三个异戊二烯单元组成的萜且具有经验式C15H24。如同单萜一样,倍半萜烯可为非环的或包含环,包括许多独特的组合。生物化学修饰如氧化或重排产生相关的类倍半萜烯。
肾上腺素能受体相互作用剂可为不饱和脂肪酸如亚油酸。在一些实施方案中,所述渗透增强剂可为法尼醇。法尼醇是一种15碳有机化合物,其是一种无环倍半萜烯醇,是法呢基焦磷酸酯的天然去磷酸化形式。在标准条件下,它是无色液体。它是疏水性的,因此不溶于水,但可与油混溶。法尼醇可以从植物油例如香茅、橙花、仙客来和晚香玉中提取。它是从脊椎动物中的甲羟戊酸生物合成胆固醇的中间步骤。它具有柔和的花香或微弱的柑橘-酸橙气味,用于香水和香料。据报道,法尼醇选择性地杀死急性髓性白血病母细胞和白血病细胞系,而不是原发性造血细胞。参见Rioja A.等人,FEBS Lett 467(2-3):291-5(2000),其通过引用并入本发明。已经报道了法呢基类似物的血管活性特性。参见Roullet,J.-B.,等人,J.Clin.Invest.,1996,97:2384-2390,其通过引用结合到本发明中。法尼醇和N-乙酰基-S-反式、反式法呢基-L-半胱氨酸(AFC),即法尼基化蛋白质的羧基末端的合成模拟物,均抑制大鼠主动脉环中的血管收缩。
药物组合物可为可咀嚼的或基于明胶的剂型、喷雾剂、口香糖、凝胶、乳膏、片剂、液体或膜。该组合物可以包括例如在表面的纹理,例如微针或微突起。最近,已经显示使用微米级针来增加皮肤渗透性,从而显著增加透皮递送,包括且尤其用于大分子。大多数药物递送研究都强调了固体微针,已经证明它可以在体外增加皮肤对广泛分子和纳米颗粒的渗透性。体内研究已证明寡核苷酸的递送、胰岛素降低血糖水平、以及诱导蛋白质和DNA疫苗的免疫应答。对于这样的研究,已经使用针阵列将孔刺入皮肤以通过扩散或离子电渗疗法增加运输,或者作为从微针表面涂层将药物释放到皮肤中的药物载体。还开发了空心微针并显示其向糖尿病大鼠显微注射胰岛素。为了解决微针的实际应用,发现微针断裂力与皮肤插入力的比率(即安全边界)对于具有小尖端半径和较大壁厚度的针是最佳的。据报道,插入人类受试者皮肤的微针是无痛的。总之,这些结果表明,微针代表了一种将治疗性化合物递送到皮肤中以用于一系列可能应用的有前途的技术。使用微电子工业的工具,已经制造出具有各种尺寸、形状和材料的微针。微针可以是例如聚合的微观针,其以微创方式递送包封的药物,但是可以使用其他合适的材料。
申请人已发现微针可用于增强药物通过口腔粘膜的递送,特别是对于要求保护的组合物。微针在口腔粘膜中产生微米尺寸的孔,这可以增强药物穿过粘膜的递送。固体、中空或溶解的微针可由合适的材料制成,包括但不限于金属、聚合物、玻璃和陶瓷。微加工工艺可包括光刻、硅蚀刻、激光切割、金属电镀、金属电抛光和模塑。微针可以是固体,其用于预处理组织并在施加膜之前被移除。本申请中描述的载药聚合物膜可用作微针本身的基质材料。这些膜可以在其表面上制造微针或微突起,它们将在粘膜中形成微通道后溶解,药物可以通过该微通道渗透。
术语“膜”可包括任何形状的膜和薄片,包括矩形、正方形或其他所需形状。膜可以是任何所需的厚度和尺寸。在优选的实施方案中,膜可以具有厚度和尺寸,使得它可以施用于使用者,例如,放入使用者的口腔中。膜可以具有约0.0025mm至约0.250mm的相对薄的厚度,或者膜可以具有约0.250mm至约1.0mm的稍厚的厚度。对于一些膜,厚度可以更大,即大于约1.0mm,或更薄,即小于约0.0025mm。膜可以是单层或膜可以是多层的,包括层压或多层流延膜(cast film)。渗透增强剂和药物活性组分可以组合成单层,各自包含在单独的层中,或者可以各自包含在相同剂型的不连续区域中。在一些实施方案中,聚合物基质中包含的药物活性组分可以分散在基质中。在一些实施方案中,包含在聚合物基质中的渗透增强剂可以分散在基质中。
口服溶解膜可分为三大类:快速溶解、中度溶解和缓慢溶解。口腔溶解膜还可包括任何上述类别的组合。快速溶解膜可在口腔中在约1秒至约30秒内溶解,包括超过1秒,超过5秒,超过10秒,超过20秒,以及少于30秒。中度溶解膜可在口中在约1至约30分钟内溶解,包括超过1分钟,超过5分钟,超过10分钟,超过20分钟或少于30分钟,而缓慢溶解膜可在口腔中在超过30分钟溶解。作为一般趋势,快速溶解膜可包含(或由其组成)低分子量亲水聚合物(例如,分子量为约1,000至9,000道尔顿的聚合物,或分子量高达200,000道尔顿的聚合物)。相反,缓慢溶解的膜通常包括高分子量聚合物(例如,具有数百万的分子量)。中等溶解的膜可倾向于落入快速和慢速溶解膜之间。
可以优选使用中等溶解膜的膜。中度溶解膜可以相当快速地溶解,但也具有良好水平的粘膜粘附。中等溶解膜也可以是柔性的,可快速润湿的,并且通常对使用者无刺激性。这种中等溶解的膜可以提供足够快的溶解速率,最理想的是在约1分钟和约20分钟之间,同时提供可接受的粘膜粘附水平,使得一旦将膜放入使用者的口腔中,膜就不容易除去。这可以确保将药学活性成分递送给使用者。
药物组合物可包含一种或多种药物活性成分。药物活性成分可以是单一药物组分或药物组分的组合。药物活性成分可以是抗炎镇痛剂、甾体抗炎剂、抗组胺药、局部麻醉剂、杀菌剂、消毒剂、血管收缩剂、止血剂、化学治疗药、抗生素、角质层分离剂、烧灼剂、抗病毒药、抗风湿药、抗高血压药、支气管扩张剂、抗胆碱能药、抗焦虑药、止吐化合物、激素、肽、蛋白质或疫苗。药物活性成分可以是化合物、药物的药学上可接受的盐、前药、衍生物、药物复合物或药物类似物。术语“前药”是指生物学上无活性的化合物,其可在体内代谢以产生生物活性药物。
在一些实施方案中,多于一种药物活性成分可包含在膜中。药物活性成分可为ACE-抑制剂、抗心绞痛药、抗心律失常药、抗哮喘药、抗胆甾醇药、镇痛药、麻醉剂、抗惊厥药、抗抑郁药、抗糖尿病药、止泻制品、解毒药、抗组胺剂、抗高血压药、消炎药、抗脂药、抗狂躁药、抗恶心药、抗中风药、抗甲状腺制品、安非他明、抗肿瘤药、抗病毒剂、痤疮药、生物碱、氨基酸制品、镇咳药、抗痛风药(anti-uricemic drug)、抗病毒药、促合成代谢制品、全身和非全身性抗感染药、抗恶性肿瘤药、抗帕金森症药、抗风湿药、食欲刺激剂、血液调节剂、骨代谢调节剂、心血管药、中枢神经系统刺激剂、胆碱酯酶抑制剂、避孕药、解充血药、食品添加剂、多巴胺受体激动剂、子宫内膜异位控制剂、酶、勃起功能障碍治疗剂、致育因子、胃肠药、顺势疗法剂、激素、高血钙和低血钙症控制剂、免疫调节剂、免疫抑制剂、偏头痛药、运动病治疗剂、肌肉松弛剂、肥胖症控制剂、骨质疏松剂、催产药、副交感神经阻滞药、拟副交感神经药、前列腺素、心理治疗剂、呼吸剂、止痛药、戒烟药、交感神经阻滞药、震颤药、泌尿道药、血管扩张药、轻泻药、解酸剂、离子交换树脂、解热剂、食欲抑制药、祛痰药、抗焦虑药、抗溃疡药、抗炎药、冠状动脉扩张剂、脑扩张剂、外周血管扩张药、拟神经药物、兴奋剂、抗高血压药、血管收缩药、偏头痛治疗剂、抗生素、镇静剂、抗精神病药、抗肿瘤药、抗凝血药、抗血栓药、安眠药、止吐药、止恶心药、抗惊厥药、神经肌肉药、升血糖和降血糖药、甲状腺和抗甲状腺药、利尿剂、镇痉剂、子宫驰缓剂、抗肥胖药、促红细胞生成药、抗哮喘药、镇咳剂、粘液溶解药、DNA和基因修饰药物、诊断剂、成像剂、染料或追踪剂及其组合。
例如,药物活性成分可为丁丙诺啡、纳洛酮、对乙酰氨基酚、利鲁唑、氯巴占、利扎曲普坦、丙泊酚、水杨酸甲酯、水杨酸单乙二醇酯、阿司匹林、甲灭酸、氟芬那酸、吲哚美辛、双氯芬酸、阿氯芬酸、双氯芬酸钠、布洛芬、酮洛芬、萘普生、普拉洛芬、非诺洛芬、舒林酸、芬氯酸、环氯茚酸、氟比洛芬、芬替酸、丁苯羟酸、吡罗昔康、保泰松、羟保泰松、氯非宗、喷他佐辛、甲嘧啶唑(mepirizole)、盐酸噻拉米特、氢化可的松、强的松龙(predonisolone)、地塞米松、曲安奈德、醋酸氟轻松、醋酸氢化可的松、醋酸泼尼松龙、甲泼尼龙、醋酸地塞米松、倍他米松、戊酸倍他米松、氟米松、氟米龙、双丙酸倍氯米松、氟轻松醋酸酯、盐酸苯海拉明、水杨酸苯海拉明、苯海拉明、盐酸氯苯那敏(chiorpheniramine hydrochloride)、马来酸氯苯那敏、盐酸异西喷地、盐酸曲吡那敏、盐酸异丙嗪、盐酸甲地嗪、盐酸狄布卡因、狄布卡因、盐酸利多卡因、利多卡因、苯佐卡因、对丁基氨基苯甲酸2-(二乙氨基)乙酯盐酸盐、盐酸普鲁卡因、丁卡因、盐酸丁卡因、盐酸氯普鲁卡因、盐酸羟基普鲁卡因(oxyprocainehydrochloride)、甲哌卡因、盐酸可卡因、盐酸皮珀罗卡因、达克罗宁、盐酸达克罗宁、硫柳汞、苯酚、百里酚、苯扎氯铵、苄索氯铵、氯己定、聚维酮碘、西吡氯铵、丁子香酚、三甲基溴化铵、硝酸萘甲唑啉、盐酸四氢唑啉、盐酸羟甲唑啉、盐酸苯肾上腺素、盐酸曲马唑啉、凝血酶、植物甲萘醌、硫酸鱼精蛋白、氨基己酸、氨甲环酸、卡巴克络、卡巴克络磺酸钠(carbaxochrome sodium sulfanate)、芸香苷、橙皮苷、磺酰胺(sulfamine)、磺胺噻唑、磺胺嘧啶、磺胺米隆(homosulfamine)、磺胺异噁唑、磺胺索嘧啶、磺胺甲二唑、呋喃西林、青霉素、甲氧西林、苯唑西林、头孢噻吩、头孢噻啶(cefalordin)、红霉素、林可霉素、四环素、金霉素、土霉素、甲烯土霉素、氯霉素、卡那霉素、链霉素、庆大霉素、杆菌肽、环丝氨酸、水杨酸、鬼臼树脂、podolifox、斑蝥素、氯乙酸、硝酸银、蛋白酶抑制剂、胸苷激酶抑制剂(thymadine kinase inhibitor)、糖或糖蛋白合成抑制剂、结构蛋白合成抑制剂、附着和吸附抑制剂、和核苷类似物(如阿昔洛韦、喷昔洛韦、伐昔洛韦和更昔洛韦)、肝素、胰岛素、LHRH、TRH、干扰素、寡核苷酸(oligonuclides)、降钙素、奥曲肽、奥美拉唑、氟西汀、炔雌醇、氨氯地平、帕罗西汀、依那普利、赖诺普利、亮丙瑞林、prevastatin、洛伐他汀、炔诺酮、利培酮、奥氮平、沙丁胺醇、氢氯噻嗪、pseudoephridrine、华法林、特拉唑嗪、西沙比利、异丙托铵、busprione、哌甲酯、左甲状腺素、唑吡坦、左炔诺孕酮、格列本脲、贝那普利、甲羟孕酮、氯硝西泮、昂丹司琼、氯沙坦、喹那普利、硝基甘油、咪达唑仑针剂、西替利嗪、多沙唑嗪、格列吡嗪、乙肝疫苗、沙美特罗、舒马曲坦、曲安奈德、戈舍瑞林、倍氯米松、granisteron、去氧孕烯、阿普唑仑、雌二醇、烟碱、干扰素β1A、色甘酸钠、福辛普利、地高辛、氟替卡松、比索洛尔、calcitril、captorpril、布托啡诺、可乐定、倍美力、睾酮、舒马曲坦、克霉唑、比沙可啶、右美沙芬、硝化甘油、那法瑞林、地诺前列酮、烟碱、比沙可啶、戈舍瑞林和格拉司琼。在一些实施方案中,所述药物活性成分可为肾上腺素、苯并二氮杂环庚三烯如地西泮或劳拉西泮或阿普唑仑。
肾上腺素实例
在一个实例中,包含肾上腺素或其盐或酯的组合物可具有类似于通过注射施用的肾上腺素的生物递送特征,例如,使用EpiPen。肾上腺素可存在的量为每剂约0.01mg至约100mg,例如,0.1mg、5mg、10mg、20mg、30mg、40mg、50mg、60mg、70mg、80mg、90mg或100mg剂量、包括多于0.1mg、多于5mg、多于20mg、多于30mg、多于40mg、多于50mg、多于60mg、多于70mg、多于80mg、多于90mg、或少于100mg、少于90mg、少于80mg、少于70mg、少于60mg、少于50mg、少于40mg、少于30mg、少于20mg、少于10mg、或少于5mg、或其任意组合。在另一实例,包含地西泮的组合物可具有类似于或优于地西泮片剂或凝胶的生物递送特征。地西泮或其盐可存在的量为每剂约0.5mg至约100mg,例如,0.5mg、1mg、5mg、10mg、20mg、30mg、40mg、50mg、60mg、70mg、80mg、90mg或100mg的剂量、包括多于1mg、多于5mg、多于20mg、多于30mg、多于40mg、多于50mg、多于60mg、多于70mg、多于80mg、多于90mg、或少于100mg、少于90mg、少于80mg、少于70mg、少于60mg、少于50mg、少于40mg、少于30mg、少于20mg、少于10mg、或少于5mg,或其任意组合。
在另一实例中,组合物(例如,包括肾上腺素)可具有合适的无毒非离子烷基糖苷与粘膜递送增强剂的组合,该烷基糖苷具有疏水性烷基,所述疏水性烷基通过键与亲水性糖连接,所述粘膜递送增强剂选自:(a)聚集抑制剂;(b)电荷改性剂;(c)pH控制剂;(d)降解酶抑制剂;(e)粘液溶解或粘液清除剂;(f)纤毛稳定剂;(g)膜渗透增强剂,其选自:(i)表面活性剂;(ii)胆汁盐;(ii)磷脂添加剂、混合胶束、脂质体或载体;(iii)醇;(iv)烯胺;(v)NO供体化合物;(vi)长链两亲性分子;(vii)疏水渗透增强剂;(viii)钠或水杨酸衍生物;(ix)乙酰乙酸的甘油酯;(x)环糊精或β-环糊精衍生物;(xi)中链脂肪酸;(xii)螯合剂;(xiii)氨基酸或其盐;(xiv)N-乙酰氨基酸或其盐;(xv)对选定的膜组分降解的酶;(ix)脂肪酸合成抑制剂;(x)胆固醇合成抑制剂;和(xi)(i)-(x)中所述的膜渗透增强剂的任何组合;(h)上皮连接生理学的调节剂;(i)血管扩张剂;(j)选择性运输增强剂;或(k)稳定递送工具、载体、粘膜粘着剂、支持体或复合物形成剂,由此化合物被有效地组合、联合、包含、包封、或结合,导致该化合物的稳定性,以增强粘膜递送,其中用跨粘膜递送增强剂配制化合物提供了受试者血浆内增加的化合物生物利用率。该制剂可包含与地西泮和阿普唑仑的另一实例大概相同的活性药物成分(API):增强剂的比例。
膜和/或其组分可为水溶性、水溶胀性或水不溶性。术语“水溶性”可意指至少部分可溶于水性溶剂中的物质,包括但不限于水。术语“水溶性”不必指物质为100%溶于水性溶剂。术语“水不溶性”是指不溶于水性溶剂中的物质,包括但不限于水。溶剂可包括水,或可包括其它溶剂(优选地,极性溶剂)本身或与水的组合。
该组合物可包括聚合物基质。可以使用任何所需的聚合物基质,条件是它可口服溶解或可蚀。剂型应具有足够的生物粘附性以不易除去,并且当施用时应形成凝胶状结构。它们可以在口腔中适度溶解并且特别适合于递送药物活性组分,但快速释放、延迟释放、控释和持续释放组合物也在所考虑的各种实施方案中。
支化聚合物
药物组合物膜可包含树枝状聚合物,其可包括具有各种结构的高度支化的大分子。树枝状聚合物可包括树枝状聚合物、树枝化聚合物(树枝状接枝(dendrigrafted)聚合物)、线性树枝状杂化物、多臂星形聚合物或超支化聚合物。
超支化聚合物是高度支化的聚合物,其结构存在缺陷。然而,它们可以在单步反应中合成,这可以优于其他树枝状结构,因此适用于批量应用。除了它们的球状结构之外,这些聚合物的性质在于丰富的官能团、分子内空腔、低粘度和高溶解度。树枝状聚合物已经用于几种药物递送应用中。参见,例如,Dendrimers as Drug Carriers:Applications inDifferent Routes of Drug Administration.J Pharm Sci,VOL.97,2008,123-143,其通过引用结合到本发明中。
树枝状聚合物可具有内部空腔,其可包封药物。由高密度聚合物链引起的空间位阻可阻止药物结晶。因此,支化聚合物在配制聚合物基质中的可结晶药物方面可提供额外的优点。
合适的树枝状聚合物的实例包括基于聚(醚)的树枝状大分子(dendron)、树枝状分子和超支化聚合物,基于聚(酯)的树枝状大分子、树枝状分子和超支化聚合物,基于聚(硫醚)的树枝状大分子、树枝状分子和超支化聚合物,基于聚(氨基酸)的树枝状大分子、树枝状分子和超支化聚合物,基于聚(芳基亚烷基醚)的树枝状大分子、树枝状分子和超支化聚合物,基于聚(亚烷基亚胺)的树枝状大分子、树枝状分子和超支化聚合物,基于聚(酰氨基胺)的树枝状大分子、树枝状分子或超支化聚合物。
超支化聚合物的其它实例包括聚(胺)、聚碳酸酯、聚(醚酮)、聚氨酯、聚碳硅烷、聚硅氧烷、聚(酯胺)、聚(砜胺)、聚(脲氨基甲酸酯)和聚醚多元醇如聚甘油。
膜可以通过至少一种聚合物和溶剂的组合来制备,任选地包括其他组分。溶剂可以是水、极性有机溶剂,包括但不限于乙醇、异丙醇、丙酮或其任何组合。在一些实施方案中,溶剂可以是非极性有机溶剂,例如二氯甲烷。可以通过使用选择的浇铸或沉积方法和受控的干燥方法来制备膜。例如,可以通过受控的干燥方法制备膜,其包括向湿膜基质施加热和/或辐射能量以形成粘弹性结构,从而控制膜内容物的均匀性。受控的干燥方法可以包括使单独的空气、单独的热量或热和空气一起,在干燥过程中的同一时间或不同时间接触膜的顶部或膜的底部或支撑所浇铸或沉积或挤出的膜的基材,或者接触一个以上的表面。在美国专利No.8,765,167和美国专利No.8,652,378中更详细地描述了一些这样的方法,这些专利通过引用并入本发明。或者,可以如美国专利公开No.2005/0037055A1中所述的那样挤出膜,该专利公开通过引用结合到本发明中。
包含在膜中的聚合物可为水溶性、水可溶胀、水不溶性,或一种或多种水溶性、水可溶胀或水不溶性聚合物的组合。该聚合物可包括纤维素、纤维素衍生物或胶。可用的水溶性聚合物的具体实例包括,但不限于,聚氧化乙烯、普鲁兰多糖、羟丙基甲基纤维素、羟基乙基纤维素、羟丙基纤维素、聚乙烯吡咯烷酮、羧基甲基纤维素、聚乙烯醇、藻酸钠、聚乙二醇、黄原胶、黄蓍胶、瓜尔胶、阿拉伯树胶、阿拉伯胶、聚丙烯酸、甲基甲基丙烯酸酯共聚物、羧基乙烯基共聚物、淀粉、明胶、及其组合。可用的水不溶性聚合物的具体实例包括,但不限于,乙基纤维素、羟丙基乙基纤维素、邻苯二甲酸乙酸纤维素、羟丙基甲基纤维素邻苯二甲酸酯及其组合。对于更高的剂量,需要掺入与较低剂量相比提供高水平粘度的聚合物。
如本发明所用,短语“水溶性聚合物”及其变体是指至少部分地可溶于水,以及有利地全部或大部分可溶于水,或吸收水的聚合物。吸收水的聚合物通常被称为水可溶胀性聚合物。可与本发明一起使用的材料在室温下和其它温度(如超过室温的温度)下可为水溶性的或水可溶胀的。此外,所述材料在低于大气压的压力下可为水溶性的或水可溶胀的。在一些实施方案中,由此类水溶性聚合物形成的膜可具有足够的水溶性以在与体液接触时可溶解。
可用于掺入膜中的其它聚合物包括:可生物降解的聚合物、共聚物、嵌段聚合物或其组合。应理解,术语“可生物降解的”旨在包括化学降解的材料,与物理分解的材料相对(即生物可蚀性材料)。掺入膜中的聚合物还可包括生物可降解或生物可蚀性材料的组合。已知的满足上述标准的可用的聚合物或聚合物类别为:聚(乙醇酸)(PGA)、聚(乳酸)(PLA)、聚二噁烷、聚草酸酯、聚(α-酯)、聚酸酐、聚乙酸酯、聚己酸内酯、聚(原酸酯)、聚氨基酸、聚氨基碳酸酯、聚氨酯、聚碳酸酯、聚酰胺、聚(氰基丙烯酸烷基酯)以及它们的混合物和共聚物。其它可用的聚合物包括左旋乳酸和右旋乳酸的立体聚合物、双(对羧基苯氧基)丙烷酸和癸二酸的共聚物、癸二酸共聚物、己内酯的共聚物、聚(乳酸)/聚(乙醇酸)/聚乙二醇共聚物、聚氨酯和(聚(乳酸)的共聚物、α-氨基酸的共聚物、α-氨基酸和己酸的共聚物、α-谷氨酸苄酯和聚乙二醇的共聚物、琥珀酸酯和聚(乙二醇)的共聚物、聚磷腈、多羟基-链烷酸酯或它们的混合物。聚合物基质可包含一种、两种、三种、四种或更多种成分。
尽管可以使用多种不同的聚合物,但是希望选择对膜提供粘膜粘附性质以及所需溶解和/或崩解速率的聚合物。具体而言,膜与粘膜组织接触的期望保持时段取决于在组合物中所包含的药物活性成分的类型。一些药物活性成分可只需要几分钟便递送通过粘膜组织,而其它药物活性成分可需要高达数小时或者甚至更长的时间。因而,在一些实施方案中,如上所述的一种或多种水溶性聚合物可用于形成膜。然而,在其它实施方案中,期望使用水溶性聚合物与水可溶胀、水不溶性和/或可生物降解的聚合物的组合,如以上所提供的。包含一种或多种水可溶胀、水不溶性和/或可生物降解的聚合物可提供溶解或崩解速率比单独由水溶性聚合物形成的膜更低的膜。因此,该膜可以粘附于粘膜组织并保持较长的时间,例如最高达数小时,这对于递送一些药物活性组分而言是有利的。
理想地,药物膜的单独膜剂型可具有合适的厚度和小尺寸,其在约0.0625-3英寸×约0.0625-3英寸之间。膜尺寸也可以在至少一方面大于0.0625英寸、大于0.5英寸、大于1英寸、大于2英寸、约3英寸、以及大于3英寸、少于3英寸、少于2英寸、少于1英寸、少于0.5英寸、少于0.0625英寸,或在另一方面大于0.0625英寸、大于0.5英寸、大于1英寸、大于2英寸、或大于3英寸、约3英寸、少于3英寸、少于2英寸、少于1英寸、少于0.5英寸、或少于0.0625英寸。本领域普通技术人员可基于聚合物基质的化学和物理性质、活性药物成分、剂量、增强剂和所涉及的其它添加剂以及所需分配单元的尺寸来优化纵横比,包括厚度、长度和宽度。当放置在使用者的口腔中或舌下区域时,膜剂型应具有良好的粘附性。此外,膜剂型应以适中的速率分散和溶解,最理想的是在约1分钟内分散并在约3分钟内溶解。在一些实施方案中,膜剂型能够以约1至约30分钟的速率分散和溶解,例如,约1至约20分钟、或多于1分钟、多于5分钟、多于7分钟、多于10分钟、多于12分钟、多于15分钟、多于20分钟、多于30分钟、约30分钟、或少于30分钟、少于20分钟、少于15分钟、少于12分钟、少于10分钟、少于7分钟、少于5分钟、或少于1分钟。舌下分散速率可小于口腔分散速率。
例如,在一些实施方案中,所述膜可包含单独的聚氧化乙烯或其与第二聚合物组分的组合。第二聚合物可为另一水溶性聚合物、水可溶胀聚合物、水不溶性聚合物、生物可降解的聚合物或其任意组合。合适的水溶性聚合物包括,但不限于,以上提供的任一种。在一些实施方案中,所述水溶性聚合物可包括亲水性纤维素聚合物,如羟丙基纤维素和/或羟丙基甲基纤维素。在一些实施方案中,一种或多种水可溶胀、水不溶性和/或生物可降解的聚合物也可包含在基于聚氧化乙烯的膜中。可使用以上提供的水可溶胀、水不溶性或生物可降解的聚合物的任一种。第二聚合物组分在聚合物组分中可使用的量为约0%至约80%重量,更具体约30%至约70%重量,还更具体约40%至约60%重量,包括多于5%重量、多于10%重量、多于15%重量、多于20%重量、多于30%重量、多于40%重量、多于50%重量、多于60%重量、和多于70%重量、约70%重量、少于70%重量、少于60%重量、少于50%重量、少于40%重量、少于30%重量、少于20%重量、少于10%重量或少于5%重量。
可将添加剂包含在膜中。各类添加剂的实例包括防腐剂、抗微生物剂、赋形剂、润滑剂、缓冲剂、稳定剂、发泡剂、颜料、着色剂、填充剂、增量剂、甜味剂、调味剂、芳香剂、释放改性剂(release modifier)、佐剂、增塑剂、流动加速剂(flow accelerator)、脱模剂(moldrelease agent)、多元醇、成粒剂、稀释剂、粘结剂、缓冲液、吸收剂、助流剂、粘合剂、抗粘附剂(anti-adherent)、酸化剂、软化剂、树脂、缓和剂、溶剂、表面活性剂、乳化剂、弹性体、抗粘着剂、抗静电剂以及它们的混合物。这些添加剂可与一种或多种药物活性成分一起加入。如本发明所述,术语“稳定剂”是指能防止活性药物成分、其它赋形剂或其组合的聚集或其它物理降解以及化学降解的赋形剂。
稳定剂也可分类为抗氧化剂、螯合剂、pH修饰剂、乳化剂和/或表面活性剂和UV稳定剂。
抗氧化剂(即,药学上兼容的化合物或者组合物,其减慢、抑制、中断或者停止氧化过程)尤其包括下述物质:生育酚及其酯、芝麻油的芝麻酚、安息香树脂的松柏醇苯甲酸酯、去甲二氢愈创木树脂(nordihydroguaietic resin)和去甲二氢愈创木酸(NDGA)、没食子酸酯(甲基-、乙基-、丙基-、戊基-、丁基-、月桂基-等的没食子酸酯),丁基羟基茴香醚(BHA/BHT,还称作丁基对甲酚);抗坏血酸及其盐和酯(例如抗坏血酸棕榈酸酯)、异抗坏血酸(赤藻糖酸)及其盐和酯、硫代甘油、甲醛次硫酸氢钠、焦亚硫酸钠、亚硫酸氢钠、亚硫酸钠、偏重亚硫酸钾、丁基羟基茴香醚、丁基羟基甲苯(BHT)、丙酸。典型的抗氧化剂为如α-生育酚的生育酚和其酯,丁基羟基甲苯和丁基羟基茴香醚。术语“生育酚”也包括生育酚酯。已知的生育酚为α-生育酚。术语“α-生育酚”包括α-生育酚的酯(例如α-生育酚-醋酸酯)。
螯合剂(即,可与其他化合物例如活性成分或另一种赋形剂形成主体-客体复合物的任何化合物;也称为螯合剂)包括氯化钙、乙二胺四乙酸钙二钠、葡萄糖酸δ内酯、葡萄糖酸钠、葡萄糖酸钾、三聚磷酸钠、六偏磷酸钠及其组合。螯合剂还包括环状低聚糖、例如环糊精、cyclomannins(通过α键在1,4位连接的5个或更多个α-D-吡喃甘露糖单元)、cyclogalactins(通过β键在1,4位连接的5个或更多个β-D-吡喃半乳糖单元)、cycloaltrins(通过α键在1,4位连接的5个或更多个α-D-吡喃阿卓糖单元),及其组合。
pH调节剂包括酸(例如,酒石酸、柠檬酸、乳酸、富马酸、磷酸、抗坏血酸、乙酸、琥珀酸、己二酸和马来酸)、酸性氨基酸(例如,谷氨酸、天冬氨酸等)、该酸性物质的无机盐(碱金属盐、碱土金属盐、铵盐等)、该酸性物质与有机碱(例如,碱性氨基酸如赖氨酸、精氨酸等、葡甲胺等)的盐、和其溶剂合物(例如,水合物)。其它pH调节剂的实例包括硅化微晶纤维素、偏硅酸铝镁、磷酸的钙盐(例如,磷酸氢钙无水或水合物、钙、钠或钾的碳酸盐或碳酸氢盐和乳酸钙或其混合物)、羧基甲基纤维素的钠和/或钙盐、交联羧基甲基纤维素(例如,交联羧甲基纤维素钠和/或钙)、聚克立林钾、藻酸钠和/或藻酸钙、多库酯钠、镁、钙、铝或锌的硬脂酸盐、棕榈酸镁和油酸镁、硬脂基富马酸钠、及其组合。
乳化剂和/或表面活性剂的实例包括泊洛沙姆或普朗尼克、聚乙二醇、聚乙二醇单硬脂酸酯、聚山梨酯、月桂基硫酸钠、聚乙氧基化和氢化的蓖麻油、alkyl polyoside、疏水主链上的接枝水溶性蛋白质、卵磷脂、单硬脂酸甘油酯、单硬脂酸甘油酯/聚氧乙烯硬脂酸酯、酮硬脂醇/月桂基硫酸钠、卡波姆、磷脂、(C10-C20)-烷基和亚烷基羧酸酯、烷基醚羧酸酯、脂肪醇硫酸酯、脂肪醇醚硫酸酯、烷基酰胺硫酸酯和磺酸酯、脂肪酸烷基酰胺聚乙二醇醚硫酸酯、链烷烃磺酸酯和羟基链烷烃磺酸酯、烯烃磺酸酯、羟乙基磺酸的酰基酯、α-磺基脂肪酸酯、烷基苯磺酸酯、烷基酚乙二醇醚磺酸酯、磺基琥珀酸酯、磺基琥珀酸单酯和二酯、脂肪醇醚磷酸酯、蛋白质/脂肪酸缩合产物、烷基单甘油硫酸酯和磺酸酯、烷基甘油酯醚磺酸酯、脂肪酸氨基乙磺酸甲基(methyltauride)、脂肪酸肌氨酸酯、磺基蓖麻醇酸酯、和酰基谷氨酸酯、季铵盐(例如、二-(C10-C24)-烷基-二甲基氯化或溴化铵)、(C10-C24)-烷基-二甲基乙基氯化或溴化铵、(C10-C24)-烷基-三甲基氯化或溴化铵(例如、鲸蜡基三甲基氯化或溴化铵)、(C10-C24)-烷基-二甲基苄基氯化或溴化铵(例如、(C12—C18)-烷基-二甲基苄基氯化铵)、N—(C10-C18)-烷基-吡啶鎓氯化物或溴化物(例如、N—(C12-C16)-烷基-吡啶鎓氯化物或溴化物)、N—(C10-C18)-烷基-异喹啉鎓氯化物、溴化物或单烷基硫酸盐、N—(C12-C18)-烷基-多羟基氨基甲酰基甲基吡啶鎓氯化物、N—(C12-C18)-烷基-N-甲基吗啉鎓氯化物、溴化物或单烷基硫酸盐、N—(C12-C18)-烷基-N-乙基吗啉鎓氯化物、溴化物或单烷基硫酸盐、(C16-C18)-烷基-五氧乙基氯化铵、二异丁基苯氧基乙氧基乙基二甲基苄基氯化铵、N,N-二乙基氨基乙基硬脂基酰胺和-油酰胺与盐酸、乙酸、乳酸、柠檬酸、磷酸的盐、N-酰基氨基乙基-N,N-二乙基-N-甲基铵的氯化物、溴化物或单烷基硫酸盐、和N-酰基氨基乙基-N,N-二乙基-N-苄基铵的氯化物、溴化物或单烷基硫酸盐(在上述之中,“酰基”表示,例如,硬脂基或油烯基(oleyl)),及其组合。
UV稳定剂的实例包括UV吸收剂(例如二苯甲酮)、UV猝灭剂(即,将UV能量作为热量消散,而不是使能量具有降解效果的任何化合物),清除剂(即消除由暴露于UV辐射导致的自由基的任何化合物),及其组合。
在其它实施方案中,稳定剂包括抗坏血酸棕榈酸酯、抗坏血酸、α生育酚、丁基羟基甲苯、丁基羟基茴香醚、半胱氨酸HC1、柠檬酸、乙二胺四乙酸(EDTA)、甲硫氨酸、柠檬酸钠、抗坏血酸钠、硫代硫酸钠、焦亚硫酸钠、亚硫酸氢钠、没食子酸丙酯、谷胱甘肽、硫代甘油、单线态氧猝灭剂、羟自由基清除剂、过氧化氢清除剂、还原剂、金属螯合剂、去污剂、离液剂及其组合。单线态氧猝灭剂包括但不限于烷基咪唑类(例如组氨酸、L-肌肽、组胺、咪唑4-乙酸)、吲哚类(例如色氨酸及其衍生物,如N-乙酰-5-甲氧基色胺、N-乙酰血清素、6-甲氧基-1,2,3,4-四氢-β-咔啉)、含硫氨基酸(例如甲硫氨酸、乙硫氨酸、黎豆氨酸、羊毛硫氨酸、N-甲酰基甲硫氨酸、猫尿氨酸、S-烯丙基半胱氨酸、S-氨乙基-L-半胱氨酸)、酚化合物(例如酪氨酸及其衍生物)、芳香酸(例如抗坏血酸、水杨酸及其衍生物)、叠氮化物(例如叠氮钠)、生育酚和相关的维生素E衍生物和胡萝卜素和相关的维生素A衍生物。“羟自由基清除剂”包括但不限于叠氮化物、二甲亚砜、组氨酸、甘露醇、蔗糖、葡萄糖、水杨酸盐和L-半胱氨酸。“过氧化氢清除剂”包括但不限于过氧化氢酶、丙酮酸盐、谷胱甘肽和谷胱甘肽过氧化物酶类。“还原剂”包括但不限于半胱氨酸和巯基乙烯。“金属螯合剂”包括但不限于EDTA、EGTA、邻菲咯啉和柠檬酸盐。“去污剂”包括但不限于SDS和十二烷基肌氨酸钠。“离液剂”包括但不限于盐酸胍、异硫氰酸盐、脲和甲酰胺。如本发明所讨论,稳定剂可存在的量为0.0001%-50%重量,包括多于0.0001%重量,多于0.001%重量,多于0.01%重量,多于0.1%重量,多于1%重量,多于5%重量,多于10%重量,多于20%重量,多于30%重量,多于40%重量,多于50%重量,少于50%重量,少于40%重量,少于30%重量,少于20%重量,少于10%重量,少于1%重量,少于0.1%重量,少于0.01%重量,少于0.001%重量,或少于0.0001%重量。
可用的添加剂可包括例如:明胶;植物蛋白,如向日葵蛋白、大豆蛋白、棉籽蛋白、花生蛋白、葡萄籽蛋白、乳清蛋白、乳清蛋白分离物、血蛋白、卵蛋白、丙烯酸化蛋白;水溶性多糖,如海藻酸盐、角叉菜胶、瓜尔胶、琼脂、黄原胶、结冷胶、阿拉伯胶和相关胶(印度树胶、刺梧桐树胶、黄耆胶)、果胶;纤维素的水溶性衍生物:烷基纤维素,羟烷基纤维素和羟烷基烷基纤维素,如甲基纤维素、羟甲基纤维素、羟乙基纤维素、羟丙基纤维素、羟乙基甲基纤维素、羟丙基甲基纤维素、羟丁基甲基纤维素;纤维素酯和羟烷基纤维素酯,如乙酸邻苯二甲酸纤维素(CAP)、羟丙基甲基纤维素(HPMC);羧烷基纤维素、羧烷基烷基纤维素、羧烷基纤维素酯,如羧甲基纤维素及它们的碱金属盐;水溶性合成聚合物,如聚丙烯酸和聚丙烯酸酯、聚甲基丙烯酸和聚甲基丙烯酸酯、聚乙酸乙烯酯、聚乙烯醇、聚乙酸邻苯二甲酸乙烯酯(polyvinylacetatephthalate)(PVAP)、聚乙烯吡咯烷酮(PVP)、PVA/乙酸乙烯酯共聚物和聚巴豆酸;合适的还有邻苯二甲酸化明胶、明胶琥珀酸酯、交联的明胶、虫胶、淀粉的水溶性化学衍生物、阳离子改性的丙烯酸酯和甲基丙烯酸酯(其具有例如叔氨基或季氨基,例如二乙基氨基乙基,需要时可以使其季铵化);或其它类似聚合物。
其它组分的范围可高达约80%,理想地约0.005%至50%,且更理想在1%至20%的范围内,基于所有组合物组分的重量,包括多于1%、多于5%、多于10%、多于20%、多于30%、多于40%、多于50%、多于60%、多于70%、约80%、多于80%、少于80%、少于70%、少于60%、少于50%、少于40%、少于30%、少于20%、少于10%、少于5%、约3%、或少于1%。其它添加剂可包括抗粘着剂、流动剂和遮光剂,如镁铝、硅、钛的氧化物等,理想地浓度范围为,基于所有膜组分的重量,约0.005%至约5%重量,且理想地约0.02%至约2%,包括多于0.02%、多于0.2%、多于0.5%、多于1%、多于1.5%、多于2%、多于4%、约5%、多于5%、少于4%、少于2%、少于1%、少于0.5%、少于0.2%、或少于0.02%。
在一些实施方案中,所述组合物可包含增塑剂,其可包括聚环氧烷、如聚乙二醇、聚丙二醇、聚乙二醇-丙二醇、具有低分子量的有机增塑剂,如甘油、甘油的单乙酸酯、二乙酸酯或三乙酸酯、三乙酸甘油酯、聚山梨酯、鲸蜡醇、丙二醇、糖醇、山梨醇、二乙基磺基琥珀酸钠、柠檬酸三乙酯、柠檬酸三丁酯、植物提取物、脂肪酸酯、脂肪酸、油等,基于组合的重量,添加的浓度范围为约0.1%至约40%,且理想地为约0.5%至约20%,包括多于0.5%、多于1%、多于1.5%、多于2%、多于4%、多于5%、多于10%、多于15%、约20%、多于20%、少于20%、少于15%、少于10%、少于5%、少于4%、少于2%、少于1%、和少于0.5%。还可以加入化合物以改善膜材料如动物或植物脂肪的质地特性,理想的是它们的氢化形式。该组合物还可以包含改善产品质地特性的化合物。其他成分可包括粘合剂,其有助于形成的容易性和膜的一般质量。粘合剂的非限制性实例包括淀粉、天然树胶、预糊化淀粉、明胶、聚乙烯吡咯烷酮、甲基纤维素、羧甲基纤维素钠、乙基纤维素、聚丙烯酰胺、聚乙烯基噁唑烷酮或聚乙烯醇。
其它潜在的添加剂包括溶解度增强剂,例如形成具有活性组分的包合化合物的物质。此类试剂可用来改善难溶和/或不稳定活性物质的特性。通常而言,这些物质是具有疏水内腔和亲水外部的环形分子。不溶性和/或不稳定药物活性成分可以配置在该疏水腔内,从而产生可溶于水的包合配合物。因此,形成包合配合物使得难溶和/或不稳定的药物活性成分可溶于水中。此类试剂的一个特别有利的实例是环糊精,其是衍生自淀粉的环状碳水化合物。然而,其它类似物质也被视作完全属于本发明的范围。
合适的着色剂包括食品、药物和化妆品色素(FD&C)、药品和化妆品色素(D&C),或外用药物和化妆品色素(Ext.D&C)。这些色素是染料、其相应的色淀以及一些天然着色剂和衍生的着色剂。色淀是吸收在氢氧化铝上的染料。着色剂的其它实例包括已知的偶氮染料、有机或无机颜料、或天然来源的着色剂。优选无机颜料,如铁或钛的氧化物,以所有组分的重量计,这些氧化物的添加浓度范围为约0.001%至约10%,并且优选约0.5%至约3%,包括多于0.001%、多于0.01%、多于0.1%、多于0.5%、多于1%、多于2%、多于5%、约10%、多于10%、少于10%、少于5%、少于2%、少于1%、少于0.5%、少于0.1%、少于0.01%、或少于0.001%。
调味剂可选自天然和合成的调味液。此类试剂的示例性清单包括挥发性油、合成调味油、调味芳香剂、油、液体、油树脂或植物、叶、花、果实、茎干的提取物,及其组合。非限制性的代表性实例清单包括薄荷油、可可油和柑橘(如柠檬、桔子、酸橙和葡萄柚)油,以及水果香精,包括苹果、梨、桃、葡萄、草莓、红莓、樱桃、李子、菠萝、杏或其它水果调味剂。其它可用的调味剂包括醛类和酯类,如苯甲醛(樱桃、杏仁)、柠檬醛,即α柠檬醛(柠檬、酸橙)、橙花醛,即β-柠檬醛(柠檬、酸橙)、癸醛(桔子、柠檬)、C-8醛(柑橘类水果)、C-9醛(柑橘类水果)、C-12醛(柑橘类水果)、甲苯基醛(樱桃、杏仁)、2,6-二甲基辛醇(绿色水果)和2-十二醛(柑橘类、桔子(mandarin)),它们的组合等。
甜味剂可选自以下非限制性清单:葡萄糖(玉米糖浆)、右旋糖、转化糖、果糖及其组合;糖精及其各种盐,如钠盐;二肽类甜味剂,如阿司帕坦,纽甜、advantame;双氢查耳酮化合物、甘草素;甜叶菊(Stevia Rebaudiana)(甜叶菊苷);蔗糖的氯化衍生物,如三氯蔗糖(sucralose);糖醇,如山梨糖醇、甘露糖醇、木糖醇等。还涵盖氢化淀粉水解物和合成甜味剂3,6-二氢-6-甲基-1-1-1,2,3-噁噻嗪-4-酮-2,2-二氧化物,特别是它的钾盐(乙酰舒泛钾)、钠盐和钙盐,以及天然的强甜味剂,如罗汉果。也可使用其它甜味剂。
消泡和/或去泡组分也可与膜一起使用。这些组分有助于将空气如夹带的空气从成膜组合物中除去。此类夹带的空气可产生不均匀的膜。二甲基硅油是一种特别有用的消泡剂和/或去泡剂。然而,本发明不限于此,并且可使用其它合适的消泡剂和/或去泡剂。二甲硅油和相关试剂可用于致密化的目的。更具体而言,此类试剂有助于除去空隙、空气、水分和类似的不利组分,从而能提供更致密且因而更均匀的膜。执行此功能的试剂或组分可称为稠化剂(densification agent)或稠密剂(densifying agent)。如上所述,夹带的空气或不利组分可产生不均匀的膜。
在上面提到的共同指定的美国专利No.7,425,292和美国专利No.8,765,167中描述的任何其他任选组分也可以包含在本发明所述的膜中。
膜组合物还优选含有缓冲剂以控制膜组合物的pH。可以将任何所需水平的缓冲剂掺入膜组合物中,以便当从组合物中释放药物活性组分时提供所需的pH水平。缓冲剂优选以足以控制药物活性组分从膜释放和/或吸收到体内的量提供。在一些实施方案中,缓冲剂可包括柠檬酸钠、柠檬酸、酒石酸氢盐及其组合。
本发明所述的药物膜可以通过任何所需的方法形成。合适的方法在美国专利号8,652,378、7,425,292和7,357,891中列出,其通过引用结合到本发明中。在一个实施方案中,通过首先制备湿组合物形成膜剂型组合物,所述湿组合物包含聚合物载体基质和治疗有效量的药物活性组分。将湿组合物浇铸成膜,然后充分干燥,形成自支撑膜组合物。湿组合物可以浇铸成单独的剂型,或者可以浇铸成片材,然后将片材切成单独的剂型。
药物组合物可粘附于粘膜表面。本发明特别用于局部治疗可具有潮湿表面并且易受体液影响的身体组织、疾病或伤口,例如口、阴道、器官或其他类型的粘膜表面。该组合物携带药物,并且在施用和粘附于粘膜表面时,提供一层保护并将药物递送至治疗部位、周围组织和其他体液。考虑到控制在水溶液或体液如唾液中的侵蚀,以及伴随递送或在递送后膜的缓慢、自然侵蚀,该组合物提供了在治疗部位有效药物递送的适当停留时间。
组合物的停留时间取决于用于制剂中的水可蚀性聚合物的消蚀速率及其各自的浓度。可以通过例如以下方法调整消蚀速率:通过将具有不同溶解度特性或化学上不同的聚合物(如羟乙基纤维素,羟丙基纤维素)混合在一起;通过使用不同分子量级的相同聚合物(如混合低分子量和中等分子量的羟乙基纤维素);通过使用具有各种不同亲脂性值或水溶解特性的赋形剂或增塑剂(包括基本上不溶的成分);通过使用水溶性有机和无机盐;通过使用用于局部交联的交联剂(如乙二醛)与聚合物(如羟乙基纤维素);或通过处理后照射或固化,这会改变所获得的膜的物理状态(包括其结晶或相变)。这些策略可以单独或组合使用,以改变膜的溶蚀动力学。在施用时,药物组合物膜粘附到粘膜表面并保持在适当位置。吸水使组合物软化,从而减少异物感。当组合物在粘膜表面上静止时,发生药物的递送。停留时间可以在很宽的范围内调节,这取决于所选药物的所需递送时间和载体的所需寿命。然而,通常,停留时间在约几秒至约几天之间调节。优选地,大多数药物的停留时间调节为约5秒至约24小时。更优选地,停留时间调节为约5秒至约30分钟。除了提供药物递送之外,一旦组合物粘附到粘膜表面,它还为治疗部位提供保护,充当可侵蚀的绷带。可以设计亲脂剂以减缓可蚀性以减少崩解和溶解。
还可以通过添加对酶(例如淀粉酶)敏感的赋形剂来调节组合物的可蚀性的动力学,所述赋形剂非常易溶于水,例如水溶性有机和无机盐。合适的赋形剂可包括钠和钾的盐酸盐、碳酸盐、碳酸氢盐、柠檬酸盐、三氟乙酸盐、苯甲酸盐、磷酸盐、氟化物、硫酸盐或酒石酸盐。添加量可以根据侵蚀动力学的改变程度以及组合物中其他组分的量和性质而变化。
通常用于上述水基乳液中的乳化剂如果是选自以下的,则优选原位获得:亚油酸、棕榈酸、肉豆蔻脑酸、月桂酸、硬脂酸、鲸蜡烯酸或油酸和氢氧化钠或氢氧化钾,或者选自山梨醇和山梨醇酐的月桂酸酯、棕榈酸酯、硬脂酸酯或油酸酯、聚氧乙烯衍生物、包括单油酸酯、单硬脂酸酯、单棕榈酸酯、单月桂酸酯、脂肪醇、烷基酚、烯丙基醚、烷基芳基醚、脱水山梨糖醇单硬脂酸酯、脱水山梨糖醇单油酸酯和/或脱水山梨糖醇单棕榈酸酯。
待使用的药物活性成分的量取决于所需的治疗强度和层的组成,但优选地,药物成分占组合物重量的约0.001%至约99%,更优选约0.003%至约75%,且最优选约0.005%至约50%、包括多于0.005%、多于0.05%、多于0.5%、多于1%、多于5%、多于10%、多于15%、多于20%、多于30%、约50%、多于50%、少于50%、少于30%、少于20%、少于15%、少于10%、少于5%、少于1%、少于0.5%、少于0.05%、或少于0.005%。其他组分的量可以根据药物或其他组分而变化,但通常这些组分占组合物总重量的不超过50%,优选不超过30%,最优选不超过15%。
膜的厚度可以根据每层的厚度和层数而变化。如上所述,可以调节层的厚度和数量以改变侵蚀动力学。优选地,如果组合物仅具有两层,则厚度范围为0.005mm至2mm,优选0.01至1mm,且更优选0.1至0.5mm,包括多于0.1mm,多于0.2mm,约0.5mm,多于0.5mm,少于0.5mm,少于0.2mm,或少于0.1mm。每层的厚度可以为层状组合物总厚度的10%至90%,并且优选为30%至60%,包括多于10%,多于20%,多于30%,多于40%,多于50%,多于70%,多于90%,约90%,少于90%,少于70%,少于50%,少于40%,少于30%,少于20%,或少于10%。因此,每层的优选厚度可以在0.01mm至0.9mm之间,或从0.03mm至0.5mm之间变化。
如本领域技术人员将理解的,当需要全身递送(例如透粘膜或透皮递送)时,治疗部位可包括膜能够递送和/或维持血液、淋巴或其他体液中所需药物水平的任何区域。通常,这种治疗部位包括口腔、耳部、眼部、肛门、鼻腔和阴道的粘膜组织,以及皮肤。如果要将皮肤用作治疗部位,则通常其中运动不会破坏膜的粘附的较大的皮肤区域是优选的,例如上臂或大腿。
药物组合物也可用作伤口敷料。通过提供物理的、相容的、可透过氧气和水分的、可以被冲走的柔韧屏障,该膜不仅可以保护伤口,还可以递送药物,以促进愈合、无菌、划伤,缓解疼痛或改善患者的总体状况。下面给出的一些实例非常适合于皮肤或伤口的应用。如本领域技术人员将理解的,该制剂可需要掺入特定的亲水/吸湿赋形剂,这有助于在延长的时间段内保持对干燥皮肤的良好粘附。当以这种方式使用时,本发明的另一个优点是,如果不希望膜在皮肤上显眼,则不需要使用染料或有色物质。另一方面,如果人们希望膜是明显的,可以使用染料或有色物质。
虽然药物组合物可粘附于粘膜组织(其本质上是潮湿组织),但它也可用于其他表面,例如皮肤或伤口。如果在施用之前皮肤被水基流体如水、唾液、伤口引流或出汗弄湿,则药物膜可粘附到皮肤上。膜可以粘附在皮肤上,直到它因与水接触而被侵蚀,例如漂洗,淋浴、洗澡或洗涤。也可以通过剥离容易地除去膜而不会对组织造成显著损害。
Franz扩散池是用于制剂开发的体外皮肤渗透测定法。Franz扩散池装置(图1A)由两个腔室组成,这两个腔室由例如动物或人体组织的膜隔开。通过顶室将测试产品施加到膜上。底部腔室包含流体,从该流体中定期取样以进行分析以确定渗透膜的活性物质的量。参照图1A,Franz扩散池100包括供体化合物101、供体室102、膜103、取样口104、接收室105,搅拌棒106和加热器/循环器107。
参考图1B,药物组合物是包含聚合物基质200的膜100,药物活性成分300包含在聚合物基质中。该膜可包括渗透增强剂400。
参考图2A和2B,该图显示活性材料从组合物中渗透。该图显示,对于原位溶解的肾上腺素碱与本身可溶的肾上腺素酒石酸氢盐,没有观察到有意义的差异。基于易加工性选择肾上腺素酒石酸氢盐进行进一步开发。根据渗透量作为时间的函数的斜率导出通量。稳态通量取自通量与时间曲线的平台乘以接收介质的体积并对渗透面积进行归一化。
参考图2A,该图显示了渗透的活性物质相对于时间的平均量,其中具有8.00mg/mL肾上腺素酒石酸氢盐和4.4mg/mL溶解的肾上腺素碱。
参考图2B,该图显示平均通量与时间的关系,其中具有8.00mg/mL酒石酸氢盐和溶解的4.4mg/mL肾上腺素碱。
参考图3,该图显示了肾上腺素酒石酸氢盐的离体渗透作为浓度的函数。该研究比较了4mg/mL、8mg/mL、16mg/mL和100mg/mL的浓度。结果表明,增加浓度导致渗透增加,并且在较高负荷下增强的水平降低。
参考图4,该图显示了肾上腺素酒石酸氢盐的渗透作为溶液pH的函数。探索酸性条件以促进稳定性。结果比较了肾上腺素酒石酸盐pH3缓冲液和肾上腺素酒石酸盐pH5缓冲液,发现肾上腺素酒石酸盐pH5缓冲液略微有利。
参考图5,该图显示了增强剂对肾上腺素渗透的影响,表示为渗透量随时间的函数。筛选了多种增强剂,包括Labrasol、capryol 90、Plurol Oleique、Labrafil、TDM、SGDC、Gelucire 44/14和丁香油。实现了对开始时间和稳态通量的显著影响,并且实现了丁香油和Labrasol的令人惊讶的增强的渗透。
参考图6A和6B,这些图显示了肾上腺素在聚合物平台上的释放和增强剂对其释放的影响,表示为渗透量(以μg计)与时间的关系。图6A显示了来自不同聚合物平台的肾上腺素释放。图6B显示增强剂对肾上腺素释放的影响。
参考图7,该图显示了雄性Yucatan小型猪的药代动力学模型。该研究比较了0.3毫克Epipen、0.12毫克肾上腺素IV和安慰剂膜。
参考图8,该图显示了无增强剂对40mg肾上腺素膜相对0.3mg Epipen的浓度分布的影响。
参考图9,该图显示增强剂A(Labrasol)对40mg肾上腺素膜相对0.3mg Epipen的浓度分布的影响。参考图10,该图显示增强剂L(丁香油)对两片40mg肾上腺素膜(10-1-1)和(11-1-1)相对0.3mg Epipen的浓度分布的影响。
参考图11,该图显示了增强剂L(丁香油)和膜尺寸(10-1-1更薄、更大的膜,11-1-1更厚、更小的膜)对40mg肾上腺素膜相对0.3mg Epipen的浓度分布的影响。
参考图12,该图显示了增强剂L(丁香油)在恒定基质中不同剂量的肾上腺素膜相对0.3mg Epipen的浓度分布。
参考图13,该图显示了增强剂L(丁香油)在恒定基质中不同剂量的肾上腺素膜相对0.3mg Epipen的浓度分布。
参考图14,该图显示了增强剂A(Labrasol)在恒定基质中不同剂量的肾上腺素膜相对0.3mg Epipen的浓度分布。
参考图15,该图显示法尼醇和法尼醇与亚油酸的组合对40mg肾上腺素膜相对0.3mg Epipen的血浆浓度分布的影响。
参考图16,该图显示法尼醇和法尼醇与亚油酸的组合对40mg肾上腺素膜相对0.3mg Epipen的血浆浓度分布的影响。
参考图17,该图显示法尼醇与亚油酸的组合对40mg肾上腺素膜相对0.3mg Epipen的血浆浓度分布的影响。
参考图18,该图显示法尼醇和法尼醇与亚油酸的组合对40mg肾上腺素膜相对0.3mg Epipen的血浆浓度分布的影响。提供以下实施例以说明本发明所述的药物组合物,以及制备和使用药物组合物和装置的方法。
实施例
实施例1
渗透增强剂-肾上腺素
使用具有16.00mg/mL浓度的肾上腺素酒石酸氢盐以及多种渗透促进剂研究渗透增强。结果显示的通量增强在下面的数据中表示。对于100%丁子香酚和100%丁香油,结果显示稳态通量显著提前,同时意外地提高了通量增强%。
1稳态通量在早得多的时间点达到
*0.3%丁子香酚相对0.3%丁香油-彼此类似的通量率
对于这些实施例,丁香油是从丁香叶中获得的。从丁香芽和/或丁香茎中的丁香油可以获得类似的结果。基于该数据,可以预期从结构上类似于肾上腺素的药物化合物可获得类似的渗透性增强结果。
实施例2
一般渗透程序–离体渗透研究方案
在一个实例中,渗透程序如下进行。将温度浴设定为37℃,将接收介质置于水浴中以调节温度并开始脱气。获得并制备Franz扩散池。Franz扩散池包括供体化合物、供体室、膜、取样口、接收室、搅拌棒和加热器/循环器。将搅拌棒插入Franz扩散池中。将组织放置在Franz扩散池上,确保组织覆盖整个区域,且与玻璃接头重叠。将扩散池的顶部放置在组织上,并将池的顶部与底部夹在一起。将约5mL受体介质加载到接收器区域中以确保在池的接收部分中没有气泡被捕获。这确保了所有5mL都可以装入接收器区域。开始搅拌,使温度平衡约20分钟。同时,高效液相色谱(HPLC)小瓶用池号和时间点标记。然后必须再次检查气泡,因为溶液在加热过程中会脱气。
如果测试膜,可以执行以下步骤:(1)称重膜,冲压以匹配扩散区域(或更小),重新称重,记录冲压前后的重量;(2)用约100μL磷酸盐缓冲液润湿供体区域;(3)将膜置于供体表面,顶部加入400μL磷酸盐缓冲液,并启动定时器。
对于溶液研究,可以执行以下步骤:(1)使用微量移液管,将500μL溶液分配到每个供体池中,启动计时器;(2)在以下时间点(时间=0分钟,20分钟,40分钟,60分钟,120分钟,180分钟,240分钟,300分钟,360分钟)取样200μL,并置于标记的HPLC小瓶中,通过敲打封闭的小瓶确保没有空气被困在小瓶的底部;(3)用200μL受体介质更换每个样品时间(保持5mL);(4)完成所有时间点后,拆开池并妥善处理所有材料。
实施例3
离体渗透评价
示例性离体渗透评价如下。
1.将组织新鲜切除并在4℃下运输(例如过夜)。
2.在使用前将组织加工并在-20℃下冷冻最多三周。
3.组织皮肤切(dermatomed)至精确的厚度。
4.将约5mL的接收介质添加到接收隔室中。选择介质以确保沉降状况。
5.将组织置于Franz扩散池中,该扩散池包括供体化合物、供体室、膜、取样口、接收室、搅拌棒和加热器/循环器。
6.施加约0.5mL供体溶液或8mm圆形膜并用500μLPBS缓冲液润湿。
7.以给定的间隔从接收室取样并用新鲜介质替换。
实施例4
多塞平的经颊递送
以下是关于多塞平的经颊递送的示例性渗透研究。这些研究在巴塞罗那大学(西班牙)动物实验伦理委员会和加泰罗尼亚(西班牙)地区自治政府动物实验委员会批准的协议下进行。使用3-4个月大的雌性猪。在使用过量的硫喷妥钠麻醉剂在Bellvitge Campus(西班牙巴塞罗那大学)的动物设施中将猪处死后,立即切除来自脸颊区域的猪颊粘膜。新鲜的颊组织在装有Hank溶液的容器中被从医院转移到实验室。将剩余的组织样品在-80℃下储存在容器中,其中具有含4%白蛋白和10%DMSO作为冷冻保护剂的PBS混合物。
对于渗透研究,将猪颊粘膜切成500+/-50μm厚的片,这有助于扩散屏障(Buccalbioadhesive drug delivery—A promising optionfor orally less efficient drugs,Sudhakar等,Journal of Controlled Release 114(2006)15–40),其使用电动皮刀(GA630,Aesculap,Tuttlingen,德国)并用手术剪刀修剪成适当的块。用手术刀除去大部分下部的结缔组织。
然后将膜安装在特殊设计的膜支架中,渗透孔直径为9mm(扩散面积为0.636cm2)。使用膜支架,将每个猪颊膜安装在供体(1.5mL)和受体(6mL)隔室之间,其上皮侧面向供体室,且结缔组织区域面向静态Franz型扩散池的接收器(Vidra Foc Barcelona,Spain)以避免泡沫形成。
通过将100μL作为供体溶液的饱和多塞平溶液施加到接收室中并通过石蜡膜立即密封以防止水蒸发来确保无限剂量条件。在进行实验之前,将扩散池在水浴中温育1小时以平衡所有池中的温度(37°+/-℃)。每个池含有小的Teflon1涂覆的磁力搅拌棒,其用于确保在实验期间受体隔室中的流体保持均匀。
通过初始测试受体介质中的多塞平饱和浓度,在所有实验中确保了沉降条件。通过注射器以预先选择的时间间隔(0.1、0.2、0.3、0.7、1、2、3、4、5和6h)从受体隔室的中心抽取样品(300μL),长达6小时。立即用相同体积的新鲜受体介质(PBS;pH 7.4)替换取出的样品体积,高度注意以避免在膜下面捕获空气。其他细节可以在A.Gimemo等人Transbuccaldelivery of doxepin:Studies on permeation and histological evaluation,International Journal of Pharmaceutics 477(2014),650-654的文章中找到,其通过引用并入本发明。
实施例5
口腔跨粘膜递送
猪口腔粘膜组织具有与人口腔粘膜组织相似的组织学特征(Heaney TG,JonesRS,Histological investigation of the influence of adult porcine alveolarmucosal connective tissues on epithelial differentiation.Arch Oral Biol 23(1978)713–717;Squier CA和Collins P,The relationship between soft tissueattachment,epithelial downgrowth and surface porosity.Journal of PeriodontalResearch 16(1981)434-440)。Lesch等(The Permeability of Human Oral Mucosa andSkin to Water,J Dent Res 68(9),1345-1349,1989)报道猪颊粘膜的水渗透性与人颊粘膜没有显著差异,但对于口腔底部,人体组织比猪组织更具渗透性。新鲜猪组织样本与在-80℃下储存的样本之间的比较显示,冷冻对渗透性没有带来显著影响。已经在体外和体内研究了多种药物分子的猪颊粘膜吸收(参见,例如,M.Sattar,Oral transmucosal drugdelivery–current status and future prospects,International Journal ofPharmaceutics 471(2014)498-506的表1),其通过引用结合到本发明中。通常,体外研究涉及将切除的猪颊组织安装在Ussing室、Franz池或类似的扩散装置中。文献中描述的体内研究涉及将药物作为溶液、凝胶或组合物施用于猪的颊粘膜,然后进行血浆取样。
Nicolazzo等(The Effect of Various inVitro Conditions on thePermeability Characteristics of the Buccal Mucosa,Journal of PharmaceuticalSciences 92(12)(2002)2399-2410)研究了各种体外条件对猪颊组织渗透性的影响,其中使用咖啡因和雌二醇作为模型亲水和亲脂分子。使用改良的Ussing室研究颊粘膜中的药物渗透。通过全厚度和上皮组织、新鲜和冷冻组织进行比较渗透研究。通过吸收异硫氰酸荧光素(FITC)标记的葡聚糖20kDa(FD20)监测组织完整性,并使用MTT(3-[4,5-二甲基噻唑-2-基]-2,5-二苯基四唑鎓溴化物)生化测定和组织学评价来评估组织活力。与全厚度颊组织相比,通过颊上皮的渗透性对于咖啡因来说是1.8倍,对于雌二醇来说是16.7倍。两种化合物的通量值对于新鲜和冷冻的颊上皮是相当的,尽管组织学评估显示了冷冻组织中细胞死亡的迹象。使用MTT活力测定,组织在死后长达12小时仍然具有活力,这也通过组织学评价确认。
Kulkarni等研究了上皮和结缔组织对猪颊组织屏障特性的相对贡献。用安替比林,丁螺环酮,布比卡因和咖啡因作为模型渗透物进行体外渗透研究。测定模型扩散剂穿过厚度为250、400、500、600和700μm的颊粘膜的渗透性。开发双层膜模型以描绘对上皮和结缔组织的屏障功能的相对贡献。随着粘膜组织厚度的增加,结缔组织区域作为渗透屏障的相对贡献显著增加。作者推荐粘膜组织厚度约为500μm以用于体外经颊渗透研究,因为上皮代表了该厚度下所有扩散剂的主要渗透屏障。作者还研究了多个生物学和实验变量对猪颊粘膜中同一组模型渗透物渗透性的影响(Porcine buccal mucosa as in vitro model:effect of biological and experimental variables,Kulkarni等,J Pharm Sci.201099(3):1265-77)。值得注意的是,与较厚的面颊(250-280μm)区域相比,对于唇部后面的较薄区域(170-220μm)观察到渗透物的较高渗透性。猪颊粘膜在4℃下在Kreb碳酸氢盐林格液中保持其完整性达24小时。与手术分离相比,将上皮与下面的结缔组织分开的热处理不会不利地影响其渗透性和完整性特征。
其他细节可以在M.Sattar,Oral transmucosal drug delivery–current statusand future prospects,International Journal of Pharmaceutics 471(2014)498-506中找到,其通过引用并入本发明。
实施例6
颊粘膜的超低温保存
猪颊粘膜的不同区域具有不同的渗透性模式,与颊部区域相比,嘴唇后面区域具有显著更高的渗透性,因为在猪颊粘膜中,上皮充当渗透屏障,并且颊上皮的厚度比嘴唇后面的区域更大(Harris和Robinson,1992)。在示例性渗透研究中,将来自相同区域的新鲜或冷冻猪颊粘膜切成500±50μm厚的片,这有助于扩散屏障(Sudhakar等,2006),其使用电动皮刀(型号GA630,Aesculap,Tuttlingen,Germany)获得并用手术剪修剪成适当的块。所有使用的装置都预先灭菌。用手术刀除去大部分潜在的结缔组织。然后将膜安装在特殊设计的膜夹持器中,其渗透孔直径为9mm(扩散面积为0.63cm2)。使用膜支架,将每个猪颊膜安装在供体(1.5mL)和受体(6mL)隔室之间,其中上皮面向供体室,结缔组织区域面向静态Franz型扩散池(Vidra Foc,Barcelona,Spain)的接收器以避免气泡形成。使用PP作为模型药物进行实验,其具有亲脂特征(logP=1.16;正辛醇/PBS,pH7.4),可电离(pKa=9.50)且MW=259.3g/mol(Modamio等,2000)。
通过将300μL作为供体溶液的PP(C0=588005±5852μg/mL,37°±1℃,n=6)在PBS(pH 7.4)中的饱和溶液施加到接收室中并立即用石蜡膜密封以防止水分蒸发,以确保无限剂量条件。
在进行实验之前,将扩散池在水浴中温育1小时以平衡所有池中的温度(37℃±1℃)。每个池包含一个小的聚四氟乙烯涂覆的磁力搅拌棒,用于确保在实验过程中受体隔室中的流体保持均匀。在初始测试受体介质中的PP饱和浓度后,在所有实验中确保了沉降条件。
通过注射器从受体隔室的中心以下列时间间隔抽取样品(300μL):0.25、0.5、1、2、3、4、5和6小时。立即用相同体积的新鲜受体介质(PBS;pH7.4)替换取出的样品体积,高度注意以避免在真皮下捕获空气。针对样品去除校正穿透粘膜的单位表面积(cm2)的药物的累积量(μg)并绘制对时间(h)的曲线。对新鲜物进行扩散实验27次,对冷冻颊粘膜进行22次扩散实验。
另外的细节可以在S.Amores,An improved cryopreservation method forporcine buccal mucosa in ex vivo drug permeation studies using Franzdiffusion cells,European Journal of Pharmaceutical Sciences 60(2014)49–54中找到。
实施例7
奎宁穿过舌下粘膜切片的渗透
由于猪和人口腔膜在组成、结构和渗透性测量方面相似,因此猪口腔粘膜是人口腔粘膜的合适模型。穿过猪口腔粘膜的渗透性不是代谢相关的,因此对组织存活来说并不重要。
为了制备猪膜,使用手术刀通过钝性解剖切除猪的口底和腹侧(下侧)的舌粘膜。将切下的粘膜切成约1cm的正方形,并在-20℃下在铝箔上冷冻直至使用(<2周)。对于猪舌的非冷冻腹面,在切除3小时内将粘膜用于渗透研究。
使用全玻璃Franz扩散池测定膜对奎宁的渗透性,标称受体体积为3.6mL,扩散面积为0.2cm2。池边缘用高性能真空润滑脂润滑,且膜安装在受体和供体隔室之间,且粘膜表面在最上面。在用pH7.4的脱气磷酸盐缓冲盐水(PBS)填充受体隔室之前,使用夹具将膜保持在适当位置。将微磁搅拌棒添加到受体隔室中,并将完整的细胞置于37℃的水浴中。将膜用施加到供体隔室的PBS平衡20分钟,然后用移液管吸出。将5μL奎宁溶液或100μL不同载体中的Q/2-HP-β-CD复合物的饱和溶液的等分试样施加于每个供体隔室。在确定唾液对奎宁穿过舌头腹侧表面的影响的研究中,在添加5μL奎宁溶液之前,将100μL无菌唾液添加到供体隔室中。
在2、4、6、8、10和12小时,从取样口取出受体相,将1mL样品的等分试样转移到HPLC自动进样器小瓶中,然后用37℃储存的新鲜PBS替换。除了涉及Q/2-HP-β-CD饱和溶液(其中在实验开始时施加无限剂量)的研究之外,将5μL的奎宁溶液分别再施加至供体相直至10小时。其目的是基于剂量间隔2小时来表示假设的使用中有限剂量给药方案。每项研究至少进行3次重复。
另外的细节可以在C.Ong,Permeation of quinine across sublingual mucosa,in vitro,International Journal of Pharmaceutics 366(2009)58–64中找到。
实施例8
离体初始研究–API的形式
在这个实施例中,测试了肾上腺素碱的渗透-原位溶解与本身可溶的肾上腺素酒石酸氢盐,没有发现差异。基于易加工性选择肾上腺素酒石酸氢盐进行进一步开发。根据随时间变化的渗透量的斜率导出通量。稳态通量从通量相对时间曲线的平台乘以接收介质的体积来推算。图2A中的图显示了平均渗透量与时间的关系,其中具有8.00mg/mL肾上腺素酒石酸氢盐和溶解的4.4mg/mL肾上腺素碱。图2B中的图显示平均通量与时间的关系,其中具有8.00mg/mL肾上腺素酒石酸氢盐和溶解的4.4mg/mL肾上腺素碱。
供体溶液 | 平均稳态通量(μg/cm<sup>2</sup>*min) |
肾上腺素碱(浓度4.4mg/mL) | 0.512 |
肾上腺素酒石酸氢盐(浓度8.00mg/mL) | 0.466 |
实施例9
渗透/通量的浓度依赖性
在该研究中,研究了肾上腺素酒石酸氢盐的离体渗透作为浓度的函数。图3显示了肾上腺素酒石酸氢盐的离体渗透作为浓度的函数。该研究比较了4mg/mL、8mg/mL、16mg/mL和100mg/mL的浓度。结果表明,增加浓度导致渗透增加,并且在较高负载下增强水平降低。该研究比较了4mg/mL、8mg/mL、16mg/mL和100mg/mL的浓度。
实施例10
pH的影响
在该实施例中,研究了肾上腺素酒石酸氢盐的渗透作为溶液pH的函数。在该实施例中,探索了酸性条件提高稳定性的能力。结果显示,与pH 3相比,pH 5略微更有利。在研究的浓度范围内,溶液中肾上腺素酒石酸氢盐的固有pH为4.5-5。不需要用缓冲液调节pH。
图4显示了肾上腺素酒石酸氢盐的渗透作为溶液pH的函数。探索酸性条件以促进稳定性。结果比较了肾上腺素酒石酸氢盐pH 3缓冲液和肾上腺素酒石酸氢盐pH5缓冲液,发现肾上腺素酒石酸氢盐pH5缓冲液略显有利。
实施例11
增强剂对肾上腺素渗透的影响
在该实施例中,研究了用于测试透粘膜递送的肾上腺素渗透,其为渗透量(μg)相对于时间(以分钟计)。在含有16.00mg/mL肾上腺素的溶液中筛选以下增强剂的浓度效应。图5中的图显示了作为时间的函数的这些增强剂的结果。
选择并设计增强剂,其功能影响粘膜中的不同屏障。虽然所有测试的增强剂确实改善了随时间渗透的量,但丁香油和Labrasol特别显示出显著且出乎意料的高渗透增强。
实施例12
增强剂对肾上腺素释放的影响
研究了肾上腺素的释放概况,以确定增强剂(Labrasol和丁香油)对肾上腺素释放的影响。图6A显示了来自不同聚合物平台的肾上腺素释放。图6B显示了增强剂对肾上腺素释放的影响。结果显示,渗透的量在约40分钟后趋于平稳,在约3250和4250μg之间。显示测试的增强剂不限制肾上腺素从基质中的释放。
实施例13
加速的稳定性
测试了负载稳定剂的变体。
实施例14
增强剂的影响
研究了雄性Yucatan小型猪的药代动力学模型。图7中的图显示了雄性Yucatan小型猪的药代动力学模型的结果。该研究比较了0.3毫克Epipen、0.12毫克肾上腺素IV和安慰剂。
无增强剂存在的影响如图8所示,其是关于没有增强剂的0.3毫克Epipen和40毫克肾上腺素膜的浓度分布。
增强剂3%Labrasol的影响显示在图9中,其显示增强剂A(Labrasol)对40mg肾上腺素膜相对0.3mg Epipen的浓度分布的影响。图10显示增强剂L(丁香油)对两片40毫克肾上腺素膜(10-1-1)和(11-1-1)相对0.3毫克Epipen的浓度分布的影响。
此外,图11还显示了膜尺寸的影响和丁香油(3%)影响。进行本研究以比较0.30mgEpiPen(n=4)、40mg肾上腺素膜(10-1-1)(n=5)和40mg肾上腺素膜(11-1-1)(n=5)。对雄性小型猪的舌下或肌内肾上腺素给药后的浓度与时间的关系。
进行研究以改变肾上腺素与增强剂的比例。这些研究也是对雄性小型猪的舌下或肌内肾上腺素给药后的浓度与时间的关系。改变肾上腺素与丁香油(增强剂L)的比例产生如图12所示的结果。进行该研究以比较0.30mg EpiPen(n=4)、40mg肾上腺素膜(12-1-1)(n=5)和20mg肾上腺素膜(13-1-1)(n=5)。
实施例15
在具有增强剂Labrasol(3%)和丁香油(3%)的恒定基质中进行变化的剂量,分别显示在图13和14中。进行图13中的研究以比较0.30mg EpiPen(n=4)、40mg肾上腺素膜(18-1-1)(n=5)和30mg肾上腺素膜(20-1-1)(n=5)。进行图14的研究以比较0.30mg EpiPen(n=4)、40mg肾上腺素膜(19-1-1)(n=5)和30mg肾上腺素膜(21-1-1)(n=5)。这些研究也是对雄性小型猪的舌下或肌内肾上腺素给药后的浓度与时间的关系。
实施例16
研究了雄性小型猪的药代动力学模型,以确定增强剂(法尼醇)对肾上腺素浓度随时间的影响。图15的图显示舌下或肌肉内给药法尼醇渗透增强剂后肾上腺素的血浆浓度(以ng/mL计)作为时间(以分钟计)的函数。本研究比较了0.3mg Epipen(n=3)、30mg肾上腺素膜31-1-1(n=5)和30mg肾上腺素膜32-1-1(n=5),每种肾上腺素膜均配制有法尼醇增强剂。如该图所示,31-1-1膜显示出增强的肾上腺素浓度稳定性,从约30-40分钟开始直至约130分钟。
图16中的图获自与图17相同的研究,但仅显示比较0.3mg Epipen与30mg肾上腺素膜31-1-1(n=5)的数据点。
图17中的图获自与图17相同的研究,但仅显示比较0.3mg Epipen与30mg肾上腺素膜32-1-1(n=5)的数据点。
实施例17
参考图18,该图显示了雄性小型猪的药代动力学模型,用于确定舌下或肌肉内给药后增强剂(法尼醇)对肾上腺素浓度随时间的影响。肾上腺素血浆浓度(以ng/mL计)显示为在肾上腺素膜中舌下或肌肉内给药法尼醇渗透增强剂后的时间(以分钟计)的函数。该研究比较了三份0.3mg Epipen相对五份30mg肾上腺素膜(32-1-1)的数据。数据显示肾上腺素膜具有增强的肾上腺素浓度稳定性,从约20-30分钟开始直至约130分钟。
实施例18
在一个实施方案中,肾上腺素药物组合物膜可以用以下配方制备:
实施例19
肾上腺素药物膜组合物使用以下配方制备:
实施例20
在另一实施方案中,药物膜组合物使用以下配方制备:
实施例21
在另一实施方案中,药物膜组合物使用以下配方制备:
实施例22
参考图19,该图显示了雄性小型猪的药代动力学模型(对数标度),用于测定舌下或肌内给药后增强剂(6%丁香油和6%Labrasol)对肾上腺素血浆浓度随时间的影响。肾上腺素血浆浓度(以ng/mL计)显示为在舌下或肌肉内给药肾上腺素膜中的法尼醇渗透增强剂后的时间(以分钟计)的函数。数据显示肾上腺素膜具有增强的肾上腺素浓度稳定性,从紧接10分钟时间点后到约30分钟开始,直到约100分钟。
参考图20,该图显示了图19中提及的雄性小型猪中的肾上腺素膜制剂的药代动力学模型,其与从0.3mg Epipen收集的平均数据(在菱形数据点中指示)比较。如数据所示,0.3mg Epipen的平均血浆浓度在0.5和1ng/mL之间达到峰值。相比之下,肾上腺素膜制剂的峰值在4到4.5ng/mL之间。
实施例23
参考图21,该图显示了雄性小型猪的药代动力学模型,研究该模型用于确定在7个动物模型中舌下或肌肉内给药后增强剂(9%丁香+3%Labrasol)对肾上腺素浓度随时间的影响。在10-30分钟之间达到一般峰值浓度。
本发明引用的所有参考文献均通过引用整体并入本发明。
其他实施方案在以下权利要求的范围内。
Claims (40)
1.一种药物组合物,其包含:
聚合物基质;
在聚合物基质中的药物活性成分,该药物活性成分包括肾上腺素;和
肾上腺素能受体相互作用剂。
2.权利要求1所述的药物组合物,进一步包含渗透增强剂。
3.根据权利要求1所述的药物组合物,其中所述组合物为进一步包含聚合物基质的膜,所述药物活性成分包含在聚合物基质中。
4.根据权利要求2所述的药物组合物,其中所述渗透增强剂包括类苯丙烷。
5.根据权利要求2所述的药物组合物,其中所述渗透增强剂包括法尼醇。
6.根据权利要求2所述的药物组合物,其中所述渗透增强剂包括Labrasol。
7.根据权利要求2所述的药物组合物,其中所述渗透增强剂包括亚油酸。
8.根据权利要求1所述的药物组合物,其中所述药物组合物为进一步包含聚合物基质的膜,所述药物活性成分包含在聚合物基质中。
9.根据权利要求1所述的药物组合物,其中所述药物组合物为可咀嚼的或基于明胶的剂型、喷雾剂、口香糖、凝胶、乳膏、片剂、液体或膜。
10.根据权利要求4所述的药物组合物,其中所述类苯丙烷为丁子香酚。
11.根据权利要求4所述的药物组合物,其中所述类苯丙烷为乙酸丁子香酚酯。
12.根据权利要求4所述的药物组合物,其中所述类苯丙烷为肉桂酸。
13.根据权利要求4所述的药物组合物,其中所述类苯丙烷为肉桂酸酯。
14.根据权利要求4所述的药物组合物,其中所述类苯丙烷为肉桂醛。
15.根据权利要求4所述的药物组合物,其中所述类苯丙烷为氢化肉桂酸。
16.根据权利要求4所述的药物组合物,其中所述类苯丙烷为佳味酚。
17.根据权利要求4所述的药物组合物,其中所述类苯丙烷为黄樟素。
18.根据权利要求1所述的药物组合物,其中所述肾上腺素能受体相互作用剂为植物提取物。
19.根据权利要求18所述的药物组合物,其中所述植物提取物进一步包括丁香植物的精油提取物。
20.根据权利要求18所述的药物组合物,其中所述植物提取物进一步包括丁香植物叶的精油提取物。
21.根据权利要求18所述的药物组合物,其中所述植物提取物进一步包括丁香植物花芽的精油提取物。
22.根据权利要求18所述的药物组合物,其中所述植物提取物进一步包括丁香植物茎的精油提取物。
23.根据权利要求18所述的药物组合物,其中所述植物提取物为合成的或生物合成的。
24.根据权利要求18所述的药物组合物,其中所述植物提取物进一步包括40-95%丁子香酚。
25.根据权利要求18所述的药物组合物,其中所述植物提取物进一步包括80-95%丁子香酚。
26.根据权利要求1所述的药物组合物,其中所述肾上腺素能受体相互作用剂包括类萜。
27.根据权利要求1所述的药物组合物,其中所述肾上腺素能受体相互作用剂包括萜。
28.根据权利要求1所述的药物组合物,其中所述肾上腺素能受体相互作用剂包括倍半萜烯。
29.根据权利要求1所述的药物组合物,其中所述聚合物基质包括聚合物。
30.根据权利要求29所述的药物组合物,其中所述聚合物为水溶性聚合物。
31.根据权利要求29所述的药物组合物,其中所述聚合物包括聚氧化乙烯。
32.根据权利要求29所述的药物组合物,其中所述聚合物包括纤维素聚合物,所述纤维素聚合物选自:羟丙基甲基纤维素、羟基乙基纤维素、羟基乙基甲基纤维素、羟丙基纤维素、甲基纤维素和羧基甲基纤维素。
33.根据权利要求29所述的药物组合物,其中所述聚合物基质包括羟丙基甲基纤维素。
34.根据权利要求29所述的药物组合物,其中所述聚合物基质包括纤维素聚合物、聚氧化乙烯和聚乙烯吡咯烷酮、聚氧化乙烯和多糖、聚氧化乙烯、羟丙基甲基纤维素和多糖、或聚氧化乙烯、羟丙基甲基纤维素、多糖和聚乙烯吡咯烷酮。
35.根据权利要求29所述的药物组合物,其中所述聚合物基质包括至少一种选自以下的聚合物:普鲁兰多糖、聚乙烯吡咯烷酮、聚乙烯醇、藻酸钠、聚乙二醇、黄原胶、黄蓍胶、瓜尔胶、阿拉伯树胶、阿拉伯胶、聚丙烯酸、甲基丙烯酸甲酯共聚物、羧基乙烯基共聚物、淀粉、明胶、环氧乙烷-环氧丙烷共聚物、胶原、白蛋白、聚氨基酸、聚磷腈、多糖、甲壳质、壳聚糖、及其衍生物。
36.根据权利要求1所述的药物组合物,进一步包含稳定剂。
37.根据权利要求29所述的药物组合物,其中所述聚合物基质包括树枝状聚合物。
38.根据权利要求29所述的药物组合物,其中所述聚合物基质包括超支化聚合物。
39.制备药物组合物的方法,包括:
将肾上腺素能受体相互作用剂与药物活性成分组合,该药物活性成分包括肾上腺素,和
形成包含该肾上腺素能受体相互作用剂和药物活性成分的药物组合物。
40.一种装置,其包含
容纳一定量的药物组合物的外壳,该药物组合物包含:
聚合物基质;
在聚合物基质中的药物活性成分,该药物活性成分包括肾上腺素;和
类苯丙烷和/或植物提取物;和
分配预定量的药物组合物的开口。
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Cited By (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN111465391A (zh) * | 2017-09-27 | 2020-07-28 | 阿奎斯蒂弗医疗股份有限公司 | 具有增强的递送的肾上腺素和前药的组合物 |
EP4302751A1 (en) * | 2022-07-07 | 2024-01-10 | LTS Lohmann Therapie-Systeme AG | Oral thin films with low water activity |
Families Citing this family (10)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2019519487A (ja) | 2016-05-05 | 2019-07-11 | アクエスティブ セラピューティクス インコーポレイテッド | 送達増強エピネフリン組成物 |
CA3022797A1 (en) * | 2016-05-05 | 2017-11-09 | Aquestive Therapeutics, Inc. | Pharmaceutical compositions with enhanced permeation |
US11273131B2 (en) | 2016-05-05 | 2022-03-15 | Aquestive Therapeutics, Inc. | Pharmaceutical compositions with enhanced permeation |
GB201709141D0 (en) | 2017-06-08 | 2017-07-26 | Klaria Pharma Holding Ab | Pharmaceutical formulation |
CA3105187A1 (en) | 2018-06-28 | 2020-01-02 | Arx, Llc | Dispensing method for producing dissolvable unit dose film constructs |
CA3110997A1 (en) * | 2018-09-07 | 2020-03-12 | Aquestive Therapeutics, Inc. | Oral film compositions and dosage forms having precise active dissolution profiles |
US20220347117A1 (en) * | 2021-03-09 | 2022-11-03 | Aquestive Therapeutics, Inc. | Dosage forms having equivalent biocomparable profiles |
JP2024510035A (ja) | 2021-03-16 | 2024-03-05 | マシェク、ヨーゼフ | エピネフリン粒子を含む複合口腔粘膜フィルム組成物 |
WO2024062423A1 (en) | 2022-09-21 | 2024-03-28 | Masek Josef | Oromucosal film compositions |
WO2024082281A1 (en) * | 2022-10-21 | 2024-04-25 | Nanjing Haiwei Pharmaceutical Technologies Co., Ltd. | Novel formulations of epinephrine and uses thereof |
Citations (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20030044446A1 (en) * | 2001-08-16 | 2003-03-06 | Mucoadhesive Erodible Drug Delivery Device For Controlled Admn. Of Pharmaceuticals & Other Acti | Mucoadhesive erodible drug delivery device for controlled administration of pharmaceuticals and other active compounds |
CN1777411A (zh) * | 2003-02-24 | 2006-05-24 | 药品生产公司 | 经粘膜药物递送系统 |
US20070202163A1 (en) * | 2005-09-09 | 2007-08-30 | Mutasem Rawas-Qalaji | Fast-disintegrating epinephrine tablets for buccal or sublingual administration |
CN101938991A (zh) * | 2007-12-07 | 2011-01-05 | 先灵-普劳健康护理产品公司 | 用于跨粘膜吸收的苯肾上腺素的药物制剂和组合物 |
US20140316333A1 (en) * | 2011-10-28 | 2014-10-23 | Sung-Yun Kwon | Dissolving solid solution perforator patch for migraine treatment |
Family Cites Families (689)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US492417A (en) | 1893-02-28 | Cake-cutter | ||
US596302A (en) | 1897-12-28 | William mcmahon | ||
US476085A (en) | 1892-05-31 | John samuel smith | ||
US26401A (en) | 1859-12-06 | Improved mode of | ||
US307537A (en) | 1884-11-04 | Dental capsicum-bag | ||
US503070A (en) | 1893-08-08 | Edward c | ||
US688446A (en) | 1901-05-20 | 1901-12-10 | Herman F Stempel Jr | Gum-plaster. |
US1110546A (en) | 1903-02-03 | 1914-09-15 | Cooper Hewitt Electric Co | Directional-current arrester. |
US1827354A (en) | 1929-04-03 | 1931-10-13 | Cooper Tea Packet Company | Packet-package and dispensing apparatus |
US2142537A (en) | 1936-07-22 | 1939-01-03 | Rare Chemicals Inc | Anesthetic ointment |
US2277038A (en) | 1937-10-30 | 1942-03-24 | Curtis David | Anesthetic preparation |
US2352691A (en) | 1941-07-25 | 1944-07-04 | Curtis David | Anesthetic compound and preparation |
US2376656A (en) | 1942-05-20 | 1945-05-22 | American Maize Prod Co | Dispersion of gums |
US2501544A (en) | 1946-10-23 | 1950-03-21 | Shellmar Products Corp | Therapeutic product |
US2612165A (en) | 1950-11-27 | 1952-09-30 | Joseph J Szuderski | Medicated pacifier |
US3007848A (en) | 1958-03-12 | 1961-11-07 | Vol Pak Inc | Method of forming an edible medicinal wafer strip package |
US3044338A (en) | 1958-04-21 | 1962-07-17 | Charles E Horton | Sterile gauze dispenser with cutting means thereon |
NL247796A (zh) | 1959-01-27 | 1900-01-01 | ||
US3142217A (en) | 1961-05-12 | 1964-07-28 | Clarence E Busse | Cutter for dispenser of aluminum foil and like material |
US3131068A (en) | 1961-07-24 | 1964-04-28 | American Cyanamid Co | Water-soluble coated edible organic acids |
US3237596A (en) | 1961-09-18 | 1966-03-01 | Smith Kline French Lab | Apparatus for coating discrete solids |
US3189174A (en) | 1962-01-12 | 1965-06-15 | Ethicon Inc | Surgical supply package |
US3242959A (en) | 1963-05-02 | 1966-03-29 | Henry P Glass | Means for carrying and displaying cards |
US3249109A (en) | 1963-11-01 | 1966-05-03 | Maeth Harry | Topical dressing |
GB1061557A (en) | 1964-04-01 | 1967-03-15 | Ashe Chemical Ltd | New impregnated or coated films |
US3324754A (en) | 1964-07-20 | 1967-06-13 | Peavy Alton | Dispenser for packets, packages or envelopes and the like |
GB1142325A (en) | 1965-05-14 | 1969-02-05 | Higham Stanley Russell | Means for administering drugs |
GB1154317A (en) | 1965-06-15 | 1969-06-04 | Higham Stanley Russell | Oral Vehicle for Administering Drugs by Buccal Absorption |
FR1586811A (zh) | 1966-01-06 | 1970-03-06 | ||
US3370497A (en) | 1966-03-08 | 1968-02-27 | Clarence E. Busse | Cutting means for dispenser of sheet material |
US3419137A (en) | 1967-11-14 | 1968-12-31 | Bard Inc C R | Closed-end peel package |
US3539605A (en) | 1968-01-30 | 1970-11-10 | Nalco Chemical Co | Ion exchange method of preparing quaternary ammonium compounds |
US3632740A (en) | 1968-06-13 | 1972-01-04 | Johnson & Johnson | Topical device for the therapeutic management of dermatological lesions with steroids |
US3451539A (en) | 1968-08-07 | 1969-06-24 | Hoerner Waldorf Corp | Circular type disc |
US3998215A (en) | 1968-12-18 | 1976-12-21 | Minnesota Mining And Manufacturing Company | Bio-medical electrode conductive gel pads |
US3536809A (en) | 1969-02-17 | 1970-10-27 | Alza Corp | Medication method |
US3797494A (en) | 1969-04-01 | 1974-03-19 | Alza Corp | Bandage for the administration of drug by controlled metering through microporous materials |
US3598122A (en) | 1969-04-01 | 1971-08-10 | Alza Corp | Bandage for administering drugs |
US3610248A (en) | 1969-04-16 | 1971-10-05 | Woodstream Hydron Corp | Gum exercise device |
US3625351A (en) | 1969-04-22 | 1971-12-07 | Melvin I Eisenberg | A sterilized tearable bag |
US3650461A (en) | 1970-02-16 | 1972-03-21 | Reynolds Metals Co | Easy open pouch construction |
US3640741A (en) | 1970-02-24 | 1972-02-08 | Hollister Inc | Composition containing gel |
US3892905A (en) | 1970-08-12 | 1975-07-01 | Du Pont | Cold water soluble plastic films |
US3641237A (en) | 1970-09-30 | 1972-02-08 | Nat Patent Dev Corp | Zero order release constant elution rate drug dosage |
US3755558A (en) | 1971-02-23 | 1973-08-28 | Du Pont | Polylactide drug mixtures for topical application atelet aggregation |
US3677866A (en) | 1971-03-04 | 1972-07-18 | Bio Medical Sciences Inc | Dispenser for disposable type thermometers |
US3753732A (en) | 1971-04-19 | 1973-08-21 | Merck & Co Inc | Rapidly disintegrating bakery enrichment wafer |
US3731683A (en) | 1971-06-04 | 1973-05-08 | Alza Corp | Bandage for the controlled metering of topical drugs to the skin |
US3996934A (en) | 1971-08-09 | 1976-12-14 | Alza Corporation | Medical bandage |
BE789477A (fr) | 1971-10-01 | 1973-01-15 | Colgate Palmolive Co | Procede de fabrication de dentifrices exempts de gaz |
US4251400A (en) | 1971-11-03 | 1981-02-17 | Borden, Inc. | Hot and cold water redispersible polyvinyl acetate adhesives |
US3768725A (en) | 1971-11-11 | 1973-10-30 | Nat Distillers Chem Corp | Breathable, sterilizable and peelable pouch and method of manufacture thereof |
US3814095A (en) | 1972-03-24 | 1974-06-04 | H Lubens | Occlusively applied anesthetic patch |
US3835995A (en) | 1972-07-12 | 1974-09-17 | Paco Packaging | Tamperproof package |
US3809220A (en) | 1972-07-24 | 1974-05-07 | Becton Dickinson Co | Child safety package |
US3825014A (en) | 1972-08-21 | 1974-07-23 | Reddy Co Inc | Pacifier |
US3809714A (en) | 1972-08-31 | 1974-05-07 | Interx Research Corp | Novel ester of ((methylamino)methyl) benzyl alcohol |
US3795527A (en) | 1973-04-23 | 1974-03-05 | Continental Can Co | Dry powder paper size having improved resistance to caking |
US3933245A (en) | 1973-07-09 | 1976-01-20 | Mullen Patrick E | Article holding and dispensing container |
US4067116A (en) | 1973-12-26 | 1978-01-10 | Caterpillar Tractor Co. | Geometric pitch determining device |
US3979839A (en) | 1974-01-08 | 1976-09-14 | Paul Marie Michel Jean Blanie | Drug interaction system |
US3911099A (en) | 1974-01-23 | 1975-10-07 | Defoney Brenman Mayes & Baron | Long-acting articles for oral delivery and process |
US4022924A (en) | 1974-05-13 | 1977-05-10 | General Foods Corporation | Dry acidulents |
US4015023A (en) | 1974-05-31 | 1977-03-29 | Lever Brothers Company | Foods with substituted succinic acid compounds |
DE2449865B2 (de) | 1974-10-17 | 1981-06-19 | Schering Ag Berlin Und Bergkamen, 1000 Berlin | Folienförmiges Arzneimittel |
US4136145A (en) | 1974-07-05 | 1979-01-23 | Schering Aktiengesellschaft | Medicament carriers in the form of film having active substance incorporated therein |
IN142428B (zh) | 1974-07-05 | 1977-07-09 | Schering Ag | |
US4136162A (en) | 1974-07-05 | 1979-01-23 | Schering Aktiengesellschaft | Medicament carriers in the form of film having active substance incorporated therein |
DE2432925C3 (de) | 1974-07-05 | 1985-11-21 | Schering AG, 1000 Berlin und 4709 Bergkamen | Folienförmige Arzneimittel |
US4049848A (en) | 1974-12-13 | 1977-09-20 | United Foam Corporation | Textured-foam coated urethane wall and ceiling covering and method of making the same |
US3972995A (en) | 1975-04-14 | 1976-08-03 | American Home Products Corporation | Dosage form |
GB1491272A (en) | 1975-09-10 | 1977-11-09 | Lingner & Fischer Gmbh | Polymer adhesive compositions containing gelling agents |
US4029757A (en) | 1975-12-15 | 1977-06-14 | Hoffmann-La Roche Inc. | Manufacture of pharmaceutical unit dosage forms |
US4029758A (en) | 1975-12-15 | 1977-06-14 | Hoffmann-La Roche Inc. | Preparation of pharmaceutical unit dosage forms |
US4031200A (en) | 1975-12-15 | 1977-06-21 | Hoffmann-La Roche Inc. | Manufacture of pharmaceutical unit dosage forms |
PH13712A (en) | 1975-12-15 | 1980-09-09 | Hoffmann La Roche | Novel dosage forms |
AU514195B2 (en) | 1975-12-15 | 1981-01-29 | F. Hoffmann-La Roche & Co. | Dosage form |
US4123592A (en) | 1976-04-07 | 1978-10-31 | Philip Morris Incorporated | Process for incorporating flavorant into cellulosic substrates and products produced thereby |
US4053046A (en) | 1976-07-29 | 1977-10-11 | Jno H. Swisher & Son, Inc. | Plastic film wrapper |
US4105116A (en) | 1976-10-29 | 1978-08-08 | Beatrice Foods Co. | Sample-containing envelope assembly |
JPS5385000A (en) | 1976-12-31 | 1978-07-26 | Akira Misaki | Glucan and its preparation |
US4139627A (en) | 1977-10-06 | 1979-02-13 | Beecham Inc. | Anesthetic lozenges |
DE2746414A1 (de) | 1977-10-15 | 1979-04-26 | Gerlach Eduard Chem Fab | Mittel zum dosieren von stoffen und verfahren zu seiner herstellung |
US4145441A (en) | 1977-11-04 | 1979-03-20 | Interx Research Corporation | Sympathomimetic amines exhibiting anti-hemorrhoidal activity |
US4675009A (en) | 1977-11-07 | 1987-06-23 | Lec Tec Corporation | Drug dispensing device for transdermal delivery of medicaments |
SE7713618L (sv) | 1977-12-01 | 1979-06-02 | Astra Laekemedel Ab | Lokalanestetisk blandning |
SE424955B (sv) | 1978-06-16 | 1982-08-23 | Hesselgren Sven Gunnar | Retentionspreparat for tandproteser |
JPS5562012A (en) | 1978-11-06 | 1980-05-10 | Teijin Ltd | Slow-releasing preparation |
US4341563A (en) | 1978-11-17 | 1982-07-27 | Sankyo Company Limited | Protective coating compositions |
US4198390A (en) | 1979-01-31 | 1980-04-15 | Rider Joseph A | Simethicone antacid tablet |
GB2042888B (en) | 1979-03-05 | 1983-09-28 | Teijin Ltd | Preparation for administration to the mucosa of the oral or nasal cavity |
US4284194A (en) | 1979-03-12 | 1981-08-18 | American Cyanamid Company | Package for a multiple of sterile sutures with or without needles attached |
US4284534A (en) | 1979-04-03 | 1981-08-18 | Jack S. Wachtel | Aqueous bubble blowing composition |
US4713239A (en) | 1979-05-29 | 1987-12-15 | Vsesojuny Kardiologichesky Nauchny Tsentr Adkaemii Meditsinski Nauk Sssr | Antianginal film and method of treating ischemic heart disease |
US4251561A (en) | 1979-06-04 | 1981-02-17 | General Mills, Inc. | Low-moisture, frangible aerated confections and method of preparation |
JPS55164685A (en) | 1979-06-08 | 1980-12-22 | Takeda Chem Ind Ltd | Novel maytansinoid compound and its preparation |
US4249531A (en) | 1979-07-05 | 1981-02-10 | Alza Corporation | Bioerodible system for delivering drug manufactured from poly(carboxylic acid) |
SE431092B (sv) | 1979-07-10 | 1984-01-16 | Thuresson Af Ekenstam Bo | Terapeutiskt aktiva, substituerade piperidinkarboxianilider |
US4291015A (en) | 1979-08-14 | 1981-09-22 | Key Pharmaceuticals, Inc. | Polymeric diffusion matrix containing a vasodilator |
US4307075A (en) | 1979-09-13 | 1981-12-22 | American Home Products Corporation | Topical treatment of aphthous stomatitis |
JPS56100714A (en) | 1980-01-16 | 1981-08-12 | Teijin Ltd | Pharmaceutical adhering to oral mucous membrane or nasal mucous membrane |
JPS5933361Y2 (ja) | 1980-03-14 | 1984-09-18 | 日東電工株式会社 | 電極パッド |
US4307117A (en) | 1980-03-27 | 1981-12-22 | General Foods Corporation | Stabilized curcumin colorant |
US4390450A (en) | 1980-07-30 | 1983-06-28 | A. E. Staley Manufacturing Company | Proteinaceous foaming compositions and method for preparing foamed proteinaceous products |
JPS5758615A (en) | 1980-09-26 | 1982-04-08 | Nippon Soda Co Ltd | Film agnent and its preparation |
US4503070A (en) | 1981-07-31 | 1985-03-05 | Eby Iii George A | Method for reducing the duration of the common cold |
US4365423A (en) | 1981-03-27 | 1982-12-28 | Eastman Kodak Company | Method and apparatus for drying coated sheet material |
US4787517A (en) | 1981-04-06 | 1988-11-29 | Martin Andrew Mcg | Easily opened and reclosable bag with tear-guiding ridges |
US4432975A (en) | 1981-04-13 | 1984-02-21 | Icn Pharmaceuticals, Inc. | Process for introducing vitamin B-12 into the bloodstream |
AU550098B2 (en) | 1981-05-02 | 1986-03-06 | Smith & Nephew Associated Companies Plc | Sterile dressing |
DK260782A (da) | 1981-06-12 | 1982-12-13 | Nat Res Dev | Hydrogeler |
US4373036A (en) | 1981-12-21 | 1983-02-08 | Block Drug Company, Inc. | Denture fixative composition |
US4460562A (en) | 1982-01-06 | 1984-07-17 | Key Pharmaceuticals, Inc. | Polymeric diffusion matrix containing propranolol |
JPS58134019A (ja) | 1982-02-05 | 1983-08-10 | Ono Pharmaceut Co Ltd | プロスタグランジン含有持続放出型三層状フイルム製剤及びその製造方法 |
US4511592A (en) | 1982-03-11 | 1985-04-16 | Scm Corporation | Preparation of acidulated meat emulsions |
US4451260A (en) | 1982-03-26 | 1984-05-29 | Minnesota Mining And Manufacturing Company | Sustained release oral medicinal delivery device |
US4460532A (en) | 1982-05-17 | 1984-07-17 | Cornell Richard R | Method for making moldings using a fixed shaping die |
JPS58206751A (ja) | 1982-05-26 | 1983-12-02 | 日石三菱株式会社 | 創傷被覆材 |
US4568535A (en) | 1982-08-06 | 1986-02-04 | Loesche Walter J | Composition for periodontal administration |
US4529748A (en) | 1982-08-16 | 1985-07-16 | Richardson Gmbh | Dental prosthesis adhesive |
CA1208558A (en) | 1982-10-07 | 1986-07-29 | Kazuo Kigasawa | Soft buccal |
US4608249A (en) | 1982-11-02 | 1986-08-26 | Nitto Electric Industrial Co., Ltd. | Hydrophilic therapeutic material |
CH639619A5 (en) | 1982-12-02 | 1983-11-30 | Werner Voser | Portion pack for applying ski wax |
US4562020A (en) | 1982-12-11 | 1985-12-31 | Kabushiki Kaisha Hayashibara Seibutsu Kagaku Kenkyujo | Process for producing self-supporting glucan film |
US4478658A (en) | 1982-12-20 | 1984-10-23 | Warner-Lambert Company | Method for sealing non-enteric capsules |
US4466973A (en) | 1983-02-01 | 1984-08-21 | Thomas Rennie | Method of treating nasal and sinus congestion |
US4704119A (en) | 1983-02-03 | 1987-11-03 | Alza Corporation | Method comprising transdermal and buccal treatment of angina |
US4585452A (en) | 1983-04-12 | 1986-04-29 | Key Pharmaceuticals, Inc. | Transdermal systemic dosage forms |
JPS59222406A (ja) | 1983-06-01 | 1984-12-14 | Teijin Ltd | 歯周疾患治療用製剤及びその製造法 |
CA1247547A (en) | 1983-06-22 | 1988-12-28 | Paul Hadvary | Leucine derivatives |
US5024701A (en) | 1983-08-01 | 1991-06-18 | Hercules Incorporated | Denture adhesive composition |
US4529301A (en) | 1983-10-17 | 1985-07-16 | Rountree Philip L | Color print system |
EP0501523B1 (en) | 1983-11-14 | 1997-04-09 | Columbia Laboratories, Inc. | Bioadhesive compositions |
GB8332556D0 (en) | 1983-12-06 | 1984-01-11 | Reckitt & Colmann Prod Ltd | Analgesic compositions |
US4613497A (en) | 1984-02-29 | 1986-09-23 | Health Products Development, Inc. | Dry, water-foamable pharmaceutical compositions |
US4705174A (en) | 1984-02-29 | 1987-11-10 | Fres-Co System Usa, Inc. | Sealed flexible container with non-destructive peelable opening |
US4659714A (en) | 1984-03-27 | 1987-04-21 | Dentsply, Ltd. | Anesthetic methods for mammals |
CA1248450A (en) | 1984-04-05 | 1989-01-10 | Kazuo Kigasawa | Soft patch |
EP0159604B1 (en) | 1984-04-09 | 1990-11-07 | Toyo Boseki Kabushiki Kaisha | Sustained-release preparation applicable to mucous membrane in oral cavity |
JPS60219238A (ja) | 1984-04-14 | 1985-11-01 | Hayashibara Biochem Lab Inc | 徐崩性プルラン含有成形物とその製法 |
US4727064A (en) | 1984-04-25 | 1988-02-23 | The United States Of America As Represented By The Department Of Health And Human Services | Pharmaceutical preparations containing cyclodextrin derivatives |
US4963367A (en) | 1984-04-27 | 1990-10-16 | Medaphore, Inc. | Drug delivery compositions and methods |
DE3424538C1 (de) | 1984-07-04 | 1985-11-07 | Kulzer & Co GmbH, 6393 Wehrheim | Isoliermittel fuer Gipsformen zum Herstellen von Kunststofformlingen |
US4588592A (en) | 1984-07-18 | 1986-05-13 | Fleer Corporation | Chewing gum product and composition and process for the preparation thereof |
WO1986000814A1 (en) | 1984-07-24 | 1986-02-13 | Key Pharmaceuticals, Inc. | Adhesive transdermal dosage layer |
US4828841A (en) | 1984-07-24 | 1989-05-09 | Colorcon, Inc. | Maltodextrin coating |
JPS6160620A (ja) | 1984-09-03 | 1986-03-28 | Teijin Ltd | ピログルタミン酸エステル類を含有する医薬品組成物 |
JPS6185315A (ja) | 1984-10-04 | 1986-04-30 | Teikoku Seiyaku Kk | シ−ト状製剤 |
IE58110B1 (en) | 1984-10-30 | 1993-07-14 | Elan Corp Plc | Controlled release powder and process for its preparation |
US4593053A (en) | 1984-12-07 | 1986-06-03 | Medtronic, Inc. | Hydrophilic pressure sensitive biomedical adhesive composition |
US4752465A (en) | 1985-09-20 | 1988-06-21 | Product Resources International, Inc. | Aerosol foam |
US4639367A (en) | 1985-03-18 | 1987-01-27 | Product Resources International, Inc. | Aerosol foam |
US4748022A (en) | 1985-03-25 | 1988-05-31 | Busciglio John A | Topical composition |
US4621482A (en) | 1985-04-18 | 1986-11-11 | Naturin-Werk Becker & Co. | Method and apparatus for forming netted meat products wrapped in an edible collagen film |
US4900556A (en) | 1985-04-26 | 1990-02-13 | Massachusetts Institute Of Technology | System for delayed and pulsed release of biologically active substances |
EP0200508B1 (en) | 1985-04-27 | 1991-10-02 | Nitto Denko Corporation | Adhesive oral bandages and oral pharmaceutical preparations |
US4631837A (en) | 1985-05-31 | 1986-12-30 | Magoon Richard E | Method and apparatus for drying fruit pulp and the like |
US4661359A (en) | 1985-06-03 | 1987-04-28 | General Mills, Inc. | Compositions and methods for preparing an edible film of lower water vapor permeability |
JPS61280423A (ja) | 1985-06-05 | 1986-12-11 | Kiyuukiyuu Yakuhin Kogyo Kk | 口腔内粘膜貼付剤 |
GB8514665D0 (en) | 1985-06-11 | 1985-07-10 | Eroceltique Sa | Oral pharmaceutical composition |
US5023271A (en) | 1985-08-13 | 1991-06-11 | California Biotechnology Inc. | Pharmaceutical microemulsions |
JPS63501794A (ja) | 1985-10-09 | 1988-07-21 | デジテイン アルツナイミツテル ゲ−エムベ−ハ− | 医薬有効物質,試薬,その他の作用物質の提供ないし投与形態の製造法 |
EP0223524B1 (en) | 1985-11-08 | 1991-10-23 | Nitto Denko Corporation | Use of adhesive dermal bandages and dermal percutaneous preparations |
US4712460A (en) | 1985-11-18 | 1987-12-15 | Biotrack, Inc. | Integrated drug dosage form and metering system |
JPS62126950A (ja) | 1985-11-29 | 1987-06-09 | Unie Koroido Kk | グルコマンナンを含む可食性フイルム |
US4713251A (en) | 1985-12-18 | 1987-12-15 | Durkee Industrial Foods Corp. | Process for encapsulating liquid acids and product |
US5229164A (en) | 1985-12-19 | 1993-07-20 | Capsoid Pharma Gmbh | Process for producing individually dosed administration forms |
US4929447A (en) | 1986-01-07 | 1990-05-29 | Warner-Lambert Company | Encapsulation composition for use with chewing gum and edible products |
US4716802A (en) | 1986-01-20 | 1988-01-05 | Corfine Inc. | Scrap reduction system for rotary die cutter |
JPH0729915B2 (ja) | 1986-02-01 | 1995-04-05 | 帝國製薬株式会社 | シ−ト状口腔内貼付剤 |
US4764378A (en) | 1986-02-10 | 1988-08-16 | Zetachron, Inc. | Buccal drug dosage form |
JPH0759496B2 (ja) | 1986-03-25 | 1995-06-28 | ロ−ト製薬株式会社 | 歯周病治療剤 |
JPS62223112A (ja) | 1986-03-25 | 1987-10-01 | Rooto Seiyaku Kk | 歯周病治療剤 |
US4722761A (en) | 1986-03-28 | 1988-02-02 | Baxter Travenol Laboratories, Inc. | Method of making a medical electrode |
IL78826A (en) | 1986-05-19 | 1991-05-12 | Yissum Res Dev Co | Precursor composition for the preparation of a biodegradable implant for the sustained release of an active material and such implants prepared therefrom |
GB8613689D0 (en) | 1986-06-05 | 1986-07-09 | Euro Celtique Sa | Pharmaceutical composition |
US4713243A (en) | 1986-06-16 | 1987-12-15 | Johnson & Johnson Products, Inc. | Bioadhesive extruded film for intra-oral drug delivery and process |
USRE33093E (en) | 1986-06-16 | 1989-10-17 | Johnson & Johnson Consumer Products, Inc. | Bioadhesive extruded film for intra-oral drug delivery and process |
US4802924A (en) | 1986-06-19 | 1989-02-07 | Colorcon, Inc. | Coatings based on polydextrose for aqueous film coating of pharmaceutical food and confectionary products |
US4648509A (en) | 1986-07-14 | 1987-03-10 | Alves Dario M | Tamper-proof package and method |
GB2193891B (en) | 1986-08-18 | 1990-07-25 | Sandoz Ltd | Nasal pharmaceutical composition containing a somatostatin anologue. |
DE3630603A1 (de) | 1986-09-09 | 1988-03-10 | Desitin Arzneimittel Gmbh | Darreichungs- und dosierungsform fuer arzneimittelwirkstoffe, reagentien oder dergleichen sowie verfahren zu deren herstellung |
US4781294A (en) | 1986-10-08 | 1988-11-01 | Warner-Lambert Company | Tear oriented package |
US4762230A (en) | 1986-10-08 | 1988-08-09 | Warner-Lambert Company | Tear oriented package |
JPH0739508B2 (ja) | 1986-11-11 | 1995-05-01 | 株式会社林原生物化学研究所 | プルラン・ポリエチレングリコ−ル会合物とその製造方法並びに用途 |
JPH0744940B2 (ja) | 1986-12-24 | 1995-05-17 | ライオン株式会社 | 口腔貼付用基材 |
US4851394A (en) | 1986-12-30 | 1989-07-25 | Uni Colloid Kabushiki Kaisha | Glucomannan/polyhydric alcohol composition and film prepared therefrom |
FR2608942B1 (fr) | 1986-12-31 | 1991-01-11 | Centre Nat Rech Scient | Procede de preparation de systemes colloidaux dispersibles d'une substance, sous forme de nanocapsules |
WO1988007103A1 (en) | 1987-03-11 | 1988-09-22 | Valmet Paper Machinery Inc. | Arrangement for drying a running web |
US4950689A (en) | 1987-03-31 | 1990-08-21 | Yang Robert K | Pectin delivery system |
US4860754A (en) | 1987-04-01 | 1989-08-29 | E. R. Squibb & Sons, Inc. | Electrically conductive adhesive materials |
US5028632A (en) | 1987-04-20 | 1991-07-02 | Fuisz Pharmaceutical Ltd. | Taste masked medicated pharmaceutical |
DE3714074A1 (de) | 1987-04-28 | 1988-11-10 | Hoechst Ag | Grundlage fuer schleimhaut- und prothesenhaft-pasten, verfahren zu ihrer herstellung sowie pasten auf basis dieser grundlage |
US4780309A (en) | 1987-06-16 | 1988-10-25 | Warner-Lambert Company | Edible aerosol foam compositions and method of preparing same |
CH672996A5 (zh) | 1987-06-26 | 1990-01-31 | Battelle Memorial Institute | |
US5107734A (en) | 1987-07-22 | 1992-04-28 | Armbruster Joseph M | Electrically powered dispenser for rolled sheet material |
DE3726797A1 (de) | 1987-08-12 | 1989-02-23 | Bayer Ag | Arzneimittel fuer den bereich der mundhoehle |
EP0303445A1 (en) | 1987-08-13 | 1989-02-15 | Walton S.A. | Clebopride transdermal patch |
US4927634A (en) | 1987-12-16 | 1990-05-22 | Richardson-Vicks Inc. | Pharmaceutical compositions containing dyclonine HC1 and phenol |
US4888354A (en) | 1987-12-21 | 1989-12-19 | Theratech, Inc. | Skin penetration enhancement using free base and acid addition salt combinations of active agents |
JPH0710702Y2 (ja) | 1988-01-29 | 1995-03-15 | ジューキ株式会社 | ミシンの布送り装置 |
US4915950A (en) | 1988-02-12 | 1990-04-10 | Cygnus Research Corporation | Printed transdermal drug delivery device |
US5234957A (en) | 1991-02-27 | 1993-08-10 | Noven Pharmaceuticals, Inc. | Compositions and methods for topical administration of pharmaceutically active agents |
US4872270A (en) | 1988-03-09 | 1989-10-10 | Eastman Kodak Company | Drying process |
US5025692A (en) | 1988-03-25 | 1991-06-25 | Reynolds Doug J | Cutter for wall covering sheet rolls |
US4900552A (en) | 1988-03-30 | 1990-02-13 | Watson Laboratories, Inc. | Mucoadhesive buccal dosage forms |
US4861632A (en) | 1988-04-19 | 1989-08-29 | Caggiano Michael A | Laminated bag |
US5047244A (en) | 1988-06-03 | 1991-09-10 | Watson Laboratories, Inc. | Mucoadhesive carrier for delivery of therapeutical agent |
US4876970A (en) | 1988-07-29 | 1989-10-31 | Wendy Bolduc | Coin operated infant changing table |
US4937078A (en) | 1988-08-26 | 1990-06-26 | Mezei Associates Limited | Liposomal local anesthetic and analgesic products |
US4948580A (en) | 1988-12-08 | 1990-08-14 | E. R. Squibb & Sons, Inc. | Muco-bioadhesive composition |
US5700479A (en) | 1988-12-23 | 1997-12-23 | Guidor Ab | Surgical element and method for selective tissue regeneration |
DE3843844C1 (zh) | 1988-12-24 | 1990-02-01 | Deutsche Gelatine-Fabriken Stoess & Co Gmbh, 6930 Eberbach, De | |
JPH0645536B2 (ja) | 1989-01-31 | 1994-06-15 | 日東電工株式会社 | 口腔粘膜貼付剤および口腔粘膜貼付製剤 |
JP2656338B2 (ja) | 1989-01-31 | 1997-09-24 | 日東電工株式会社 | 口腔粘膜貼付製剤 |
US4910247A (en) | 1989-03-27 | 1990-03-20 | Gaf Chemicals Corporation | Adhesive composition |
JPH02258718A (ja) | 1989-03-31 | 1990-10-19 | Nippon Kayaku Co Ltd | ペースト状基剤及び製剤 |
JP2708869B2 (ja) | 1989-04-04 | 1998-02-04 | 不二製油株式会社 | 透明な可食性フィルムの製造方法 |
US5064717A (en) | 1989-04-28 | 1991-11-12 | Kanzaki Paper Manufacturing Co., Ltd. | Adhesive sheet |
US5089307A (en) | 1989-05-23 | 1992-02-18 | Mitsubishi Rayon Co., Ltd. | Edible film and method of making same |
JP2799435B2 (ja) | 1989-06-19 | 1998-09-17 | 富士写真フイルム株式会社 | 溶解・脱泡方法 |
US4993586A (en) | 1989-06-21 | 1991-02-19 | University Of Pittsburgh | Adhesive bandage dispensing device and associated method |
ES2044227T3 (es) | 1989-07-13 | 1994-01-01 | Oskar Altwirth | Pieza postiza adherente para protesis daentales y procedimiento para su fabricacion. |
US5079018A (en) | 1989-08-14 | 1992-01-07 | Neophore Technologies, Inc. | Freeze dry composition and method for oral administration of drugs, biologicals, nutrients and foodstuffs |
FR2651680B1 (fr) | 1989-09-14 | 1991-12-27 | Medgenix Group Sa | Nouveau procede de preparation de microparticules lipidiques. |
US5271940A (en) | 1989-09-14 | 1993-12-21 | Cygnus Therapeutic Systems | Transdermal delivery device having delayed onset |
US5230441A (en) | 1989-09-29 | 1993-07-27 | Healthtech Services Corp. | Interactive medication delivery system for pills |
US5354551A (en) | 1989-10-14 | 1994-10-11 | Desitin Arzneimittel Gmbh | Oral and dental hygiene preparation |
AU627950B2 (en) | 1989-10-14 | 1992-09-03 | Desitin Arzneimittel Gmbh | Oral and dental hygiene preparation |
DE59005373D1 (de) | 1989-10-27 | 1994-05-19 | Teich Ag Obergrafendorf | Packung für stückiges packungsgut. |
US5056584A (en) | 1989-12-07 | 1991-10-15 | Cmi International, Inc. | Method of and apparatus for pouring molds on a continuously moving conveyor |
FR2656293B1 (fr) | 1989-12-26 | 1992-06-12 | Kodak Pathe | Procede de desaeration d'une composition aqueuse et dispositif de mise en óoeuvre du procede. |
FR2657257B1 (fr) | 1990-01-19 | 1994-09-02 | Rhone Poulenc Sante | Procede de preparation de medicaments sous forme de perles. |
US5009895A (en) | 1990-02-02 | 1991-04-23 | Merck & Co., Inc. | Sustained release with high and low viscosity HPMC |
JPH03232817A (ja) | 1990-02-07 | 1991-10-16 | Showa Yakuhin Kako Kk | 貼付剤 |
US5044241A (en) | 1990-03-20 | 1991-09-03 | Labrecque Normand F | Cutting apparatus for wrap film |
JPH05506011A (ja) | 1990-04-11 | 1993-09-02 | ジ・アップジョン・カンパニー | 流動床コーティングによるイブプロフェンの味覚マスキング |
US4980169A (en) | 1990-05-03 | 1990-12-25 | Warner-Lambert Company | Flavor enhancing and increasing efficacy of cough drops |
DE4018247A1 (de) | 1990-06-07 | 1991-12-12 | Lohmann Therapie Syst Lts | Herstellungsverfahren fuer schnellzerfallende folienfoermige darreichungsformen |
US5455043A (en) | 1990-06-13 | 1995-10-03 | Fischel-Ghodsian; Fariba | Device for controlled release of vaporous medications through nasal route |
JP2810215B2 (ja) | 1990-06-15 | 1998-10-15 | 株式会社平野屋物産 | 開封容易な合成樹脂製袋 |
US5045445A (en) | 1990-06-29 | 1991-09-03 | E. I. Du Pont De Nemours And Company | Continuous in-line preparation of photographic gelatin solutions |
US5380529A (en) | 1990-07-10 | 1995-01-10 | Laboratoire Lucchini S.A. | Pharmaceutical, vaginal applicable preparation and a process for its preparation |
US5072842A (en) | 1990-10-15 | 1991-12-17 | White Ray D | Artificial nipple construction |
US5078734A (en) | 1990-10-22 | 1992-01-07 | Noble David E | Medication dispensing pacifier |
US5847023A (en) | 1990-10-26 | 1998-12-08 | Mdv Technologies, Inc. | Thermal irreversible gel corneal contact lens formed in situ |
US5196436A (en) | 1990-10-31 | 1993-03-23 | The Procter & Gamble Company | Dextromethorphan antitussive compositions |
US5149775A (en) | 1991-01-25 | 1992-09-22 | Eastman Kodak Company | Method for purifying high molecular weight vinylpyridine/styrene polymers from solution |
FR2673843B1 (fr) | 1991-03-14 | 1995-01-13 | Centre Nat Rech Scient | Composition pharmaceutique implantable, bioresorbable a base de poly(acide lactique), destinee a mettre en óoeuvre une antibiotherapie interne locale. |
US5273758A (en) | 1991-03-18 | 1993-12-28 | Sandoz Ltd. | Directly compressible polyethylene oxide vehicle for preparing therapeutic dosage forms |
NZ286242A (en) | 1991-03-26 | 1997-11-24 | Csl Ltd | Use of veterinary implant as a single dose vaccination system: rupturable polymer film coating around core of active agent and water soluble excipient |
IT1247529B (it) | 1991-04-24 | 1994-12-17 | Poli Ind Chimica Spa | Composizioni farmaceutiche in forma di schiuma per somministrazione intravaginale, cutanea e orale |
US5551033A (en) | 1991-05-17 | 1996-08-27 | Zenith Data Systems Corporation | Apparatus for maintaining one interrupt mask register in conformity with another in a manner invisible to an executing program |
IT1249315B (it) | 1991-05-23 | 1995-02-22 | Euroresearch Srl | Lamina di collageno non poroso per uso terapeutico, metodo ed apparecchiature per ottenerlo |
US5506049C1 (en) | 1991-05-24 | 2001-05-29 | World Properties Inc | Particulate filled composite film and method of making same |
IT1250421B (it) | 1991-05-30 | 1995-04-07 | Recordati Chem Pharm | Composizione farmaceutica a rilascio controllato con proprieta' bio-adesive. |
US5698155A (en) | 1991-05-31 | 1997-12-16 | Gs Technologies, Inc. | Method for the manufacture of pharmaceutical cellulose capsules |
CA2068402C (en) | 1991-06-14 | 1998-09-22 | Michael R. Hoy | Taste mask coatings for preparation of chewable pharmaceutical tablets |
DK0595894T3 (da) | 1991-07-19 | 1996-05-13 | Uniroyal Chem Co Inc | Frøfilmsammensætninger |
DE4127602A1 (de) | 1991-08-21 | 1993-02-25 | Hoechst Ag | Verfahren und vorrichtung zum beruehrungsfreien fuehren eines beschichteten materialbandes |
US5272191A (en) | 1991-08-21 | 1993-12-21 | Fmc Corporation | Cold water soluble films and film forming compositions |
JPH05197573A (ja) | 1991-08-26 | 1993-08-06 | Hewlett Packard Co <Hp> | タスク指向パラダイムによるタスク管理システム |
US5192802A (en) | 1991-09-25 | 1993-03-09 | Mcneil-Ppc, Inc. | Bioadhesive pharmaceutical carrier |
US5318780A (en) | 1991-10-30 | 1994-06-07 | Mediventures Inc. | Medical uses of in situ formed gels |
KR100198015B1 (ko) | 1991-11-01 | 1999-06-15 | 스프레이그 로버트 월터 | 이격된 별개의 패치를 코팅시키기 위한 장치 및 방법 |
JPH05147140A (ja) | 1991-11-29 | 1993-06-15 | Mitsubishi Rayon Co Ltd | 包装用フイルム |
US5176705A (en) | 1992-01-09 | 1993-01-05 | Noble David E | Medication dispensing pacifier |
FR2686020B1 (fr) | 1992-01-15 | 1994-05-13 | Oreal | Composition a usage buccal destinee a eviter la formation de taches sur les dents, leur utilisation pour l'hygiene buccale et procede d'hygiene buccale. |
JP3232488B2 (ja) | 1992-08-20 | 2001-11-26 | 株式会社林原生物化学研究所 | プルラン高含有物とその製造方法並びに用途 |
US5656297A (en) | 1992-03-12 | 1997-08-12 | Alkermes Controlled Therapeutics, Incorporated | Modulated release from biocompatible polymers |
US5759599A (en) | 1992-03-30 | 1998-06-02 | Givaudan Roure Flavors Corporation | Method of flavoring and mechanically processing foods with polymer encapsulated flavor oils |
US5334640A (en) | 1992-04-08 | 1994-08-02 | Clover Consolidated, Ltd. | Ionically covalently crosslinked and crosslinkable biocompatible encapsulation compositions and methods |
US6024975A (en) | 1992-04-08 | 2000-02-15 | Americare International Diagnostics, Inc. | Method of transdermally administering high molecular weight drugs with a polymer skin enhancer |
US5614212A (en) | 1992-04-08 | 1997-03-25 | International Medical Associates, Inc. | Method of transdermally administering high molecular weight drugs with a polymer skin enhancer |
US5286502A (en) | 1992-04-21 | 1994-02-15 | Wm. Wrigley Jr. Company | Use of edible film to prolong chewing gum shelf life |
US5656296A (en) | 1992-04-29 | 1997-08-12 | Warner-Lambert Company | Dual control sustained release drug delivery systems and methods for preparing same |
US5393528A (en) | 1992-05-07 | 1995-02-28 | Staab; Robert J. | Dissolvable device for contraception or delivery of medication |
US5472711A (en) | 1992-07-30 | 1995-12-05 | Edward Mendell Co., Inc. | Agglomerated hydrophilic complexes with multi-phasic release characteristics |
TW271400B (zh) | 1992-07-30 | 1996-03-01 | Pfizer | |
AU677231B2 (en) | 1992-08-11 | 1997-04-17 | E. Khashoggi Industries, Llc | Hydraulically settable containers |
US5506046A (en) | 1992-08-11 | 1996-04-09 | E. Khashoggi Industries | Articles of manufacture fashioned from sheets having a highly inorganically filled organic polymer matrix |
US5679145A (en) | 1992-08-11 | 1997-10-21 | E. Khashoggi Industries | Starch-based compositions having uniformly dispersed fibers used to manufacture high strength articles having a fiber-reinforced, starch-bound cellular matrix |
US5411945A (en) | 1992-08-29 | 1995-05-02 | Kabushiki Kaisha Hayashibara Seibutsu Kagaku Kenkyujo | Pullulan binder and its uses |
US5458884A (en) | 1992-09-10 | 1995-10-17 | Britton; Peter | Bioerodible device for administering active ingredients |
US5344676A (en) | 1992-10-23 | 1994-09-06 | The Board Of Trustees Of The University Of Illinois | Method and apparatus for producing nanodrops and nanoparticles and thin film deposits therefrom |
AU679937B2 (en) | 1992-11-18 | 1997-07-17 | Johnson & Johnson Consumer Products, Inc. | Extrudable compositions for topical or transdermal drug delivery |
JP2952547B2 (ja) | 1992-12-17 | 1999-09-27 | 富士写真フイルム株式会社 | 包装体 |
US5422127A (en) | 1992-12-21 | 1995-06-06 | Bristol-Myers Squibb Company | Nutritional compositions containing vitamin D esters |
US5346701A (en) | 1993-02-22 | 1994-09-13 | Theratech, Inc. | Transmucosal delivery of macromolecular drugs |
DE69407075T2 (de) | 1993-03-12 | 1998-03-26 | Fuji Photo Film Co Ltd | Umhüllter Artikel |
US6030616A (en) | 1993-03-24 | 2000-02-29 | Imperial College Of Science, Technology & Medicine | Hepatitis B escape mutant specific binding molecules |
JP3410142B2 (ja) | 1993-03-30 | 2003-05-26 | 株式会社平野屋物産 | 開封容易とした自立可能な合成樹脂製袋 |
GB9307652D0 (en) | 1993-04-14 | 1993-06-02 | Bp Chem Int Ltd | Lubricating oils |
US5342635A (en) | 1993-05-12 | 1994-08-30 | General Mills, Inc. | Puffed edible foams and high intensity microwave method of preparation |
TW332007U (en) | 1993-06-22 | 1998-05-11 | Ciba Geigy Corp | Continuous drier for board-shaped Continuous piece material and coating installation comprising such a continuous drier |
US5405637A (en) | 1993-06-30 | 1995-04-11 | Bristol-Myers Squibb Company | Milk protein partial hydrolysate and infant formula containing same |
EP0659151B1 (de) | 1993-07-08 | 1997-10-29 | Teich Aktiengesellschaft | Aufreisspackung mit aufziehlasche |
US5325968A (en) | 1993-07-14 | 1994-07-05 | Mcneil-Ppc, Inc. | Package for holding tablets |
CA2128820A1 (en) | 1993-07-27 | 1995-01-28 | Walter G. Gowan, Jr. | Rapidly disintegrating pharmaceutical dosage form and process for preparation thereof |
IL110376A (en) | 1993-08-02 | 1998-08-16 | Bristol Myers Squibb Co | Pharmaceutical preparations containing iftroban and methods for their preparation |
ZA945944B (en) | 1993-08-13 | 1996-02-08 | Eurand America Inc | Procedure for encapsulating nsaids |
WO1995005416A2 (en) | 1993-08-19 | 1995-02-23 | Cygnus Therapeutic Systems | Water-soluble pressure-sensitive mucoadhesive and devices provided therewith for emplacement in a mucosa-lined body cavity |
EP0716597A1 (en) | 1993-08-30 | 1996-06-19 | Warner-Lambert Company | Tablet coating based on a melt-spun mixture of a saccharide and apolymer |
ZA947572B (en) | 1993-09-29 | 1995-09-28 | Hampton Roads Medical College | Contraceptive compositions |
US5681873A (en) | 1993-10-14 | 1997-10-28 | Atrix Laboratories, Inc. | Biodegradable polymeric composition |
US5536158A (en) | 1993-10-25 | 1996-07-16 | Eastman Kodak Company | Apparatus for drying solvent based film |
US5407278A (en) | 1993-12-10 | 1995-04-18 | Fres-Co System Usa, Inc. | Dual compartment easily openable flexible package |
WO1995018046A1 (en) | 1993-12-28 | 1995-07-06 | Frank Richard D | Pakaging and dispensing device for sterile articles |
JPH07184548A (ja) | 1993-12-28 | 1995-07-25 | Meiji Seito Kk | 口腔用組成物 |
US5588009A (en) | 1994-02-03 | 1996-12-24 | Will; Craig A. | Personal paging, communications, and locating system |
FR2716098A1 (fr) | 1994-02-14 | 1995-08-18 | Socoplan Sa | Présentoir à sachets, par exemple pour échaantillons. |
US5479408A (en) | 1994-02-22 | 1995-12-26 | Will; Craig A. | Wireless personal paging, communications, and locating system |
GB9404248D0 (en) | 1994-03-05 | 1994-04-20 | Boots Co Plc | Pharmaceutical formulations |
US5761525A (en) | 1994-03-17 | 1998-06-02 | International Business Machines Corporation | Method and system for scheduling the playback of a multimedia presentation |
IT1273179B (it) | 1994-05-05 | 1997-07-07 | Sales Spa | Dispositivo di apertura per contenitori flessibili, contenitore provvisto di tale dispositivo e procedimento per la sua applicazione |
JPH07322812A (ja) | 1994-05-30 | 1995-12-12 | Osaka Kagaku Gokin Kk | 可食性ケーシングフィルムおよびこれを用いた加工食品の製造法 |
US5766839A (en) | 1994-06-17 | 1998-06-16 | Ysi Incorporated | Processes for preparing barrier layer films for use in enzyme electrodes and films made thereby |
US5992742A (en) | 1994-08-05 | 1999-11-30 | Sullivan; Scott L. | Pill printing and identification |
US5689550A (en) | 1994-08-08 | 1997-11-18 | Voice-Tel Enterprises, Inc. | Interface enabling voice messaging systems to interact with communications networks |
US5740231A (en) | 1994-09-16 | 1998-04-14 | Octel Communications Corporation | Network-based multimedia communications and directory system and method of operation |
US5742905A (en) | 1994-09-19 | 1998-04-21 | Bell Communications Research, Inc. | Personal communications internetworking |
US5733575A (en) | 1994-10-07 | 1998-03-31 | Bpsi Holdings, Inc. | Enteric film coating compositions, method of coating therewith, and coated forms |
DE9416958U1 (de) | 1994-10-21 | 1995-02-16 | Hengstler Gmbh | Abschneidevorrichtung mit Motor |
US5786092A (en) | 1994-11-21 | 1998-07-28 | W.R. Grace & Co.-Conn. | Peelable laminate |
US5613779A (en) | 1994-11-30 | 1997-03-25 | Kabushiki Kaisha Hosokawa Yoko | Pouch |
US5698181A (en) | 1994-12-09 | 1997-12-16 | Warner-Lambert Company | Breath-freshening edible compositions comprising menthol and an N-substituted-P-menthane carboxamide and methods for preparing same |
US5830884A (en) | 1995-01-18 | 1998-11-03 | National Starch And Chemical Investment Holding Corporation | Pharmaceutical products containing thermally-inhibited starches |
US5629021A (en) | 1995-01-31 | 1997-05-13 | Novavax, Inc. | Micellar nanoparticles |
US5573783A (en) | 1995-02-13 | 1996-11-12 | Nano Systems L.L.C. | Redispersible nanoparticulate film matrices with protective overcoats |
SE502928C2 (sv) | 1995-02-15 | 1996-02-26 | Sonny Johansson | Sätt och anordning för att torka ett fuktigt skikt med hjälp av mikrovågor |
US5605696A (en) | 1995-03-30 | 1997-02-25 | Advanced Cardiovascular Systems, Inc. | Drug loaded polymeric material and method of manufacture |
JPH08270973A (ja) | 1995-03-30 | 1996-10-18 | Mitsubishi Electric Corp | 空気調和機 |
US5750585A (en) | 1995-04-04 | 1998-05-12 | Purdue Research Foundation | Super absorbent hydrogel foams |
US5698217A (en) | 1995-05-31 | 1997-12-16 | Minnesota Mining And Manufacturing Company | Transdermal drug delivery device containing a desiccant |
US6099871A (en) | 1995-06-01 | 2000-08-08 | Bristol-Myers Squibb Company | Anti-regurgitation infant formula |
US20040209057A1 (en) | 1995-06-07 | 2004-10-21 | Enlow Howard H. | Extruded polymeric high transparency films |
US5785180A (en) | 1995-06-22 | 1998-07-28 | G. D. Searle & Co. | Child-resistant package |
US5906742A (en) | 1995-07-05 | 1999-05-25 | Usf Filtration And Separations Group Inc. | Microfiltration membranes having high pore density and mixed isotropic and anisotropic structure |
US5750145A (en) | 1995-07-28 | 1998-05-12 | Bristol-Myers Squibb Company | Stable gelatin coated aspirin tablets |
US20040265353A1 (en) | 1995-07-28 | 2004-12-30 | Zars, Inc. | Systems and methods for treating panic attacks |
FI104044B1 (fi) | 1995-07-28 | 1999-11-15 | Tapio Hurme | Hampaiden hoidossa käytettävä valmiste |
US5601605A (en) | 1995-08-29 | 1997-02-11 | Crowe; Dewey E. | Infant pacifier - fluid administering unit |
US5879690A (en) | 1995-09-07 | 1999-03-09 | Perricone; Nicholas V. | Topical administration of catecholamines and related compounds to subcutaneous muscle tissue using percutaneous penetration enhancers |
US5891461A (en) | 1995-09-14 | 1999-04-06 | Cygnus, Inc. | Transdermal administration of olanzapine |
US5641093A (en) | 1995-10-23 | 1997-06-24 | Dolin; Lisa M. | Method for dispensing pharmaceuticals |
US5766620A (en) | 1995-10-23 | 1998-06-16 | Theratech, Inc. | Buccal delivery of glucagon-like insulinotropic peptides |
JP3516539B2 (ja) | 1995-10-25 | 2004-04-05 | 富士写真フイルム株式会社 | 包装袋 |
US5771353A (en) | 1995-11-13 | 1998-06-23 | Motorola Inc. | System having virtual session manager used sessionless-oriented protocol to communicate with user device via wireless channel and session-oriented protocol to communicate with host server |
US5764899A (en) | 1995-11-13 | 1998-06-09 | Motorola, Inc. | Method and apparatus for communicating an optimized reply |
US5764639A (en) | 1995-11-15 | 1998-06-09 | Staples; Leven E. | System and method for providing a remote user with a virtual presence to an office |
US5766332A (en) | 1996-11-17 | 1998-06-16 | Maybelline, Inc. | Fast drying nail enamel composition and method |
US6238700B1 (en) | 1995-12-01 | 2001-05-29 | Alza Corporation | Method for preventing crystal formation in a dispersion of a liquid in a matrix |
FR2742989B1 (fr) | 1995-12-29 | 1998-01-23 | Adir | Composition pharmaceutique bioadhesive pour la liberation controlee de principes actifs |
US5815398A (en) | 1996-01-16 | 1998-09-29 | Massachusettes Institute Of Technology | Method and apparatus for placing parts in a bounded region |
USD380836S (en) | 1996-01-18 | 1997-07-08 | Playtex Products, Inc. | Pacifier |
US5912007A (en) | 1996-02-29 | 1999-06-15 | Warner-Lambert Company | Delivery system for the localized administration of medicaments to the upper respiratory tract and methods for preparing and using same |
DE69722191T2 (de) | 1996-03-08 | 2004-04-01 | Nycomed Danmark Aps | Dosiszusammensetzung mit modifizierter freigabe aus vielen einzelkomponenten |
US5846557A (en) | 1996-03-20 | 1998-12-08 | Cumberland Packing Corporation | Chewing gum containing cough suppressing agent |
EP0890068A1 (en) | 1996-03-29 | 1999-01-13 | Minnesota Mining And Manufacturing Company | Apparatus and method for drying a coating on a substrate employing multiple drying subzones |
US5937161A (en) | 1996-04-12 | 1999-08-10 | Usa.Net, Inc. | Electronic message forwarding system |
EP0834047A1 (en) | 1996-04-18 | 1998-04-08 | Infrarödteknik AB | Method and device for drying a moving web material |
US5864684A (en) | 1996-05-22 | 1999-01-26 | Sun Microsystems, Inc. | Method and apparatus for managing subscriptions to distribution lists |
EP0910348B1 (en) | 1996-05-23 | 2003-04-02 | Samyang Corporation | Locally administrable, biodegradable and sustained-release pharmaceutical composition for periodontitis and process for preparation thereof |
US5822526A (en) | 1996-06-03 | 1998-10-13 | Microsoft Corporation | System and method for maintaining and administering email address names in a network |
US6440464B1 (en) | 1996-06-10 | 2002-08-27 | Viva Life Science | Nutritive composition for cardiovascular health containing fish oil, garlic, rutin, capsaicin, selenium, vitamins and juice concentrates |
DK1014941T3 (da) | 1996-06-26 | 2009-07-27 | Univ Texas | Ekstruderbar farmaceutisk hot-melt-formulering |
DE19629753A1 (de) | 1996-07-23 | 1998-01-29 | Basf Ag | Verfahren zur Herstellung von festen Arzneiformen |
US5792494A (en) | 1996-08-01 | 1998-08-11 | L. A. Dreyfus Co. | Gum base manufacturing method using elastomer emulsions |
IT1287474B1 (it) | 1996-09-13 | 1998-08-06 | Unifill Int Ag | Contenitore per un prodotto fluido |
US5725648A (en) | 1996-09-25 | 1998-03-10 | Hercules Incorporated | Paper coatings containing guar or reduced molecular weight guar |
CA2266629C (en) | 1996-10-01 | 2002-04-16 | Cima Labs Inc. | Taste-masked microcapsule compositions and methods of manufacture |
US5894930A (en) | 1996-10-10 | 1999-04-20 | Mcneil-Ppc, Inc. | Directional push and peel easy to open child resistant blister package |
US5862915A (en) | 1996-10-10 | 1999-01-26 | Mcneil-Ppc, Inc. | Cavity assist easy to open child resistant blister package |
US5800832A (en) | 1996-10-18 | 1998-09-01 | Virotex Corporation | Bioerodable film for delivery of pharmaceutical compounds to mucosal surfaces |
US5955097A (en) | 1996-10-18 | 1999-09-21 | Virotex Corporation | Pharmaceutical preparation applicable to mucosal surfaces and body tissues |
US20010006677A1 (en) | 1996-10-29 | 2001-07-05 | Mcginity James W. | Effervescence polymeric film drug delivery system |
DE19646392A1 (de) | 1996-11-11 | 1998-05-14 | Lohmann Therapie Syst Lts | Zubereitung zur Anwendung in der Mundhöhle mit einer an der Schleimhaut haftklebenden, Pharmazeutika oder Kosmetika zur dosierten Abgabe enthaltenden Schicht |
DE19646836B4 (de) | 1996-11-13 | 2006-06-14 | Lts Lohmann Therapie-Systeme Ag | Zubereitung, bestehend aus einer flächenhaften, film- oder oblatenartigen Darreichungsform |
DE19652188C2 (de) | 1996-12-16 | 2002-02-14 | Lohmann Therapie Syst Lts | Flache Arzneizubereitung zur Applikation und Freisetzung von Buprenorphin oder einer pharmakologisch vergleichbaren Substanz in der Mundhöhle und Verfahren zu ihrer Herstellung |
FI2850U1 (fi) | 1996-12-20 | 1997-04-25 | Pentti Alanen | Tutti |
US6183808B1 (en) | 1997-01-06 | 2001-02-06 | Bpsi Holdings, Inc. | Film coatings and film coating compositions based on dextrin |
US5995597A (en) | 1997-01-21 | 1999-11-30 | Woltz; Robert Thomas | E-mail processing system and method |
US6004996A (en) | 1997-02-05 | 1999-12-21 | Hoffman-La Roche Inc. | Tetrahydrolipstatin containing compositions |
US6152007A (en) | 1997-02-05 | 2000-11-28 | Japan Cbm Corporation | Sheet cutter |
US5806284A (en) | 1997-03-03 | 1998-09-15 | Apothecus Pharmaceutical Corp. | Method and system for producing sealed packages of a film which is dissolved in a body fluid |
US6090800A (en) * | 1997-05-06 | 2000-07-18 | Imarx Pharmaceutical Corp. | Lipid soluble steroid prodrugs |
US6143276A (en) | 1997-03-21 | 2000-11-07 | Imarx Pharmaceutical Corp. | Methods for delivering bioactive agents to regions of elevated temperatures |
US6074097A (en) | 1997-04-28 | 2000-06-13 | Dai Nippon Printing Co., Ltd. | Package, package manufacturing method and package manufacturing system for carrying out the package manufacturing method |
US5980554A (en) | 1997-05-05 | 1999-11-09 | Micro Therapeutics, Inc. | Wire frame partial flow obstruction for aneurysm treatment |
US6248391B1 (en) | 1997-07-16 | 2001-06-19 | Bpsi Holdings, Inc. | Bright white film coatings and film coating compositions therefor |
US5945651A (en) | 1997-07-17 | 1999-08-31 | Chorosinski; Leonard | Remotely programmable medication dispensing system |
US6153210A (en) | 1997-08-14 | 2000-11-28 | Periodontix, Inc. | Use of locally delivered metal ions for treatment of periodontal disease |
GB2328443B (en) | 1997-08-21 | 2001-09-05 | Reckitt & Colmann Prod Ltd | In situ formation of pharmaceutically acceptable polymeric material |
KR100551221B1 (ko) | 1997-09-09 | 2006-02-10 | 리오트로픽테라피우틱스 인코퍼레이션 | 코팅된 입자, 그 제조방법 및 그 사용방법 |
US6161129A (en) | 1997-09-30 | 2000-12-12 | At&T Corp. | Unlisted address messaging system |
US20040136914A1 (en) | 1997-10-01 | 2004-07-15 | Dugger Harry A. | Buccal, polar and non-polar spray containing ondansetron |
EP1027036A2 (en) | 1997-10-03 | 2000-08-16 | ELAN CORPORATION, Plc | Taste masked formulations |
US20050048102A1 (en) | 1997-10-16 | 2005-03-03 | Virotex Corporation | Pharmaceutical carrier device suitable for delivery of pharmaceutical compounds to mucosal surfaces |
JP3335569B2 (ja) | 1997-10-31 | 2002-10-21 | 花王株式会社 | シート状パック包装体及びその製造方法 |
US6221402B1 (en) | 1997-11-20 | 2001-04-24 | Pfizer Inc. | Rapidly releasing and taste-masking pharmaceutical dosage form |
US5891845A (en) | 1997-11-21 | 1999-04-06 | Fuisz Technologies Ltd. | Drug delivery systems utilizing liquid crystal structures |
EP1041988A4 (en) | 1997-12-22 | 2002-03-13 | Euro Celtique Sa | METHOD FOR PREVENTING ABUSE OF OPIOID DOSES FORMS |
US6541606B2 (en) | 1997-12-31 | 2003-04-01 | Altus Biologics Inc. | Stabilized protein crystals formulations containing them and methods of making them |
IL137179A0 (en) | 1998-01-05 | 2001-07-24 | Tecksom Internat Ltd | Easy tearing bags and packaging material |
DE19800682B4 (de) | 1998-01-10 | 2004-07-08 | Lts Lohmann Therapie-Systeme Ag | Verfahren zur Herstellung einer Primärverpackung für film- oder oblatenförmige Darreichungsformen |
US6072100A (en) | 1998-01-28 | 2000-06-06 | Johnson & Johnson Consumer Products, Inc. | Extrudable compositions for topical or transdermal drug delivery |
UA65607C2 (uk) | 1998-03-04 | 2004-04-15 | Орто-Макнейл Фармацевтикал, Інк. | Фармацевтична композиція (варіанти) та спосіб її приготування |
JP4030177B2 (ja) | 1998-03-09 | 2008-01-09 | 大日本印刷株式会社 | 包装袋 |
US5965154A (en) | 1998-03-17 | 1999-10-12 | Plc Holding, L.L.C. | Adhesive matrix type transdermal patch and method of manufacturing same |
AT405717B (de) | 1998-03-18 | 1999-11-25 | Bamed Ag | Schnuller-sauger |
FR2776187B1 (fr) | 1998-03-23 | 2000-05-05 | Oreal | Composition solide deodorante |
US6200604B1 (en) | 1998-03-27 | 2001-03-13 | Cima Labs Inc. | Sublingual buccal effervescent |
US6064990A (en) | 1998-03-31 | 2000-05-16 | International Business Machines Corporation | System for electronic notification of account activity |
US6036016A (en) | 1998-04-20 | 2000-03-14 | Pinnacle Intellectual Property Services, Inc. | Blister package with easy tear blister |
US6103266A (en) | 1998-04-22 | 2000-08-15 | Tapolsky; Gilles H. | Pharmaceutical gel preparation applicable to mucosal surfaces and body tissues |
DE69923675T2 (de) | 1998-04-29 | 2006-05-11 | Virotex Corp., Fort Collins | Pharmazeutische trägervorrichtung welche zur verabreichung von wirkstoffen an schleimhautoberflächen geeignet ist |
US6219694B1 (en) | 1998-05-29 | 2001-04-17 | Research In Motion Limited | System and method for pushing information from a host system to a mobile data communication device having a shared electronic address |
US6287595B1 (en) | 1998-06-10 | 2001-09-11 | Delsys Pharmaceuticals Corporation | Biomedical assay device |
US6432460B1 (en) | 1998-06-12 | 2002-08-13 | General Mills, Inc. | Food product and method of preparation |
US20020127254A1 (en) | 1998-06-25 | 2002-09-12 | Lavipharm Laboratories Inc. | Devices for local and systemic delivery of active substance and methods of manufacturing thereof |
US6099865A (en) | 1998-07-08 | 2000-08-08 | Fmc Corporation | Croscarmellose taste masking |
US6047484A (en) | 1998-07-10 | 2000-04-11 | Bolland; Karin Marie | Method and apparatus for evaporating liquid from a product |
US6228920B1 (en) | 1998-07-10 | 2001-05-08 | Kimberly-Clark Woldwide, Inc. | Compositions and process for making water soluble polyethylene oxide films with enhanced toughness and improved melt rheology and tear resistance |
US5941393A (en) | 1998-07-23 | 1999-08-24 | Sonoco Development, Inc. | Easy opening plastic bag pack of the star-seal type |
US6599542B1 (en) | 1998-08-11 | 2003-07-29 | Warner-Lambert Company | Non-stick chewing gum base |
US6596298B2 (en) | 1998-09-25 | 2003-07-22 | Warner-Lambert Company | Fast dissolving orally comsumable films |
US6230894B1 (en) | 1998-10-22 | 2001-05-15 | Novartis Pharmaceuticals Corp. | Child resistant package and method of dispensing medication |
US6277407B1 (en) | 1998-11-10 | 2001-08-21 | Frederick S. Marius | Apparatus and method for tablet fabrication |
US6177092B1 (en) | 1998-11-10 | 2001-01-23 | Color Access, Inc. | Self-foaming cleansing systems |
JP2000159658A (ja) | 1998-11-27 | 2000-06-13 | Lion Corp | 厚み均等な乾燥膜の製造方法 |
US6344088B1 (en) | 1998-12-16 | 2002-02-05 | Matsushita Electric Industrial Co., Ltd. | Stripe coating applicator and method |
US6374715B1 (en) | 1998-12-18 | 2002-04-23 | Hitachi Metals, Ltd. | Apparatus for punching sheet |
US6797283B1 (en) | 1998-12-23 | 2004-09-28 | Alza Corporation | Gastric retention dosage form having multiple layers |
US6077558A (en) | 1998-12-23 | 2000-06-20 | Bristol-Myers Squibb Company | Elemental nutritional products |
AR022137A1 (es) | 1998-12-31 | 2002-09-04 | Kimberly Clark Co | Una composicion de materia, una pelicula y un articulo que comprenden dicha composicion |
US6552024B1 (en) | 1999-01-21 | 2003-04-22 | Lavipharm Laboratories Inc. | Compositions and methods for mucosal delivery |
US6800329B2 (en) | 1999-02-12 | 2004-10-05 | Lts Lohmann Therapie-Systeme Ag | Method for producing film-type dosage |
JP4812167B2 (ja) | 1999-02-12 | 2011-11-09 | モレキュラー インサイト ファーマスーティカルズ インコーポレイテッド | 薬物輸送用マトリックス、ならびにその作成方法および使用方法 |
GB9904629D0 (en) | 1999-03-02 | 1999-04-21 | Danbiosyst Uk | Oral drug delivery system |
US6468516B1 (en) | 1999-03-19 | 2002-10-22 | Warner-Lambert Company | Composition and manufacture of topical pharmaceutical and cosmetic semi-solid post-foaming dosage forms in a pouch |
NZ514890A (en) | 1999-03-31 | 2003-05-30 | Janssen Pharmaceutica Nv | Pregelatinized starch in a controlled release formulation |
US6090401A (en) | 1999-03-31 | 2000-07-18 | Mcneil-Ppc, Inc. | Stable foam composition |
US6294206B1 (en) | 1999-04-09 | 2001-09-25 | Abbott Laboratories | Powdered human milk fortifier |
US6509072B2 (en) | 1999-04-27 | 2003-01-21 | P. Scott Bening | Multi-layer film with periodic barrier coating and methods of making and using such film |
US6197329B1 (en) | 1999-05-03 | 2001-03-06 | Drugtech Corporation | Anti-nausea compositions and methods |
US6231957B1 (en) | 1999-05-06 | 2001-05-15 | Horst G. Zerbe | Rapidly disintegrating flavor wafer for flavor enrichment |
AU5844300A (en) | 1999-06-04 | 2000-12-28 | Indian Council Of Medical Research | Eugenia jambolina fruit extracts for treating diabetes |
US6375963B1 (en) | 1999-06-16 | 2002-04-23 | Michael A. Repka | Bioadhesive hot-melt extruded film for topical and mucosal adhesion applications and drug delivery and process for preparation thereof |
EP1066825A1 (en) | 1999-06-17 | 2001-01-10 | The Procter & Gamble Company | An anti-microbial body care product |
US20020076440A1 (en) | 1999-06-25 | 2002-06-20 | Thomas Leon | Veterinary delivery systems and methods of delivering effective agents to animals |
JP2001068446A (ja) | 1999-06-30 | 2001-03-16 | Applied Materials Inc | 半導体ウェーハの汚染物質の検出 |
DE19932603A1 (de) | 1999-07-13 | 2001-01-25 | Gruenenthal Gmbh | Wirkstoffhaltiger Mehrschichtfilm aus in situ vernetzten hydrophilen Polymeren |
JP4270663B2 (ja) | 1999-08-03 | 2009-06-03 | 大日本印刷株式会社 | 易開封性包装袋 |
US6562375B1 (en) | 1999-08-04 | 2003-05-13 | Yamanouchi Pharmaceuticals, Co., Ltd. | Stable pharmaceutical composition for oral use |
US6264981B1 (en) | 1999-10-27 | 2001-07-24 | Anesta Corporation | Oral transmucosal drug dosage using solid solution |
DE19954245A1 (de) | 1999-11-11 | 2001-07-19 | Lohmann Therapie Syst Lts | Mehrschichtige filmförmige Zubereitung aus hydrophilen Polymeren zur schnellen Freisetzung von Wirkstoffen |
DE19954420A1 (de) | 1999-11-12 | 2001-05-31 | Lohmann Therapie Syst Lts | Zubereitung, bestehend aus einer film-, folien- oder oblatenförmigen Darreichungsform mit zweischichtigem Aufbau und integrierter Kennzeichnung |
US20050042271A1 (en) | 1999-11-19 | 2005-02-24 | Xel Herbaceuticals, Inc . | Transdermal delivery system for alkaloids of aconitum species |
EP1062873A1 (en) | 1999-12-13 | 2000-12-27 | N.V. Nutricia | Improved infant formula, protein hydrolysate for use in such an infant formula, and method for producing such a hydrolysate |
DE19960154A1 (de) | 1999-12-14 | 2001-07-12 | Lohmann Therapie Syst Lts | Flache Arzneizubereitung zur transmucosalen Verabreichung von Oxycodon oder einem vergleichbaren Wirkstoff in der Mundhöhle, für die Anwendung in der Schmerztherapie und Suchttherapie |
US20030124176A1 (en) | 1999-12-16 | 2003-07-03 | Tsung-Min Hsu | Transdermal and topical administration of drugs using basic permeation enhancers |
KR20010057582A (ko) | 1999-12-23 | 2001-07-04 | 미쉘 지. 멘지니 | 수용성 필름 제조방법 |
GB0002339D0 (en) | 2000-02-02 | 2000-03-22 | Crompton J R Plc | Beverage infusion packages and materials therefor |
US6365218B1 (en) | 2000-02-04 | 2002-04-02 | Abbott Laboratories | Pediatric formula and methods for providing nutrition and improving tolerance |
JP2001225851A (ja) | 2000-02-16 | 2001-08-21 | Okayama Taiho Pharmaceutical Co Ltd | 易開封袋および破り線 |
US6227359B1 (en) | 2000-03-13 | 2001-05-08 | Russell D. Truluck | Packaging of oil-coated cutting tools |
US6905016B2 (en) | 2000-03-14 | 2005-06-14 | Noven Pharmaceuticals, Inc. | Packaging system for transdermal drug delivery systems |
GB0006432D0 (en) | 2000-03-17 | 2000-05-03 | Stanelco Fibre Optics Ltd | Capsules |
US8642051B2 (en) | 2000-03-21 | 2014-02-04 | Suzanne Jaffe Stillman | Method of hydration; infusion packet system(s), support member(s), delivery system(s), and method(s); with business model(s) and Method(s) |
MXPA02009275A (es) | 2000-03-23 | 2004-09-06 | Collaborative Technologies Inc | Metodo para preparar dispersiones de alta presion/alto esfuerzo cortante que contienen ingredientes fisiologicamente activos. |
US7067116B1 (en) | 2000-03-23 | 2006-06-27 | Warner-Lambert Company Llc | Fast dissolving orally consumable solid film containing a taste masking agent and pharmaceutically active agent at weight ratio of 1:3 to 3:1 |
JP4461310B2 (ja) | 2000-03-31 | 2010-05-12 | 小林製薬株式会社 | ゼラチン固形物 |
US6495599B2 (en) | 2000-04-13 | 2002-12-17 | Abbott Laboratories | Infant formulas containing long-chain polyunsaturated fatty acids and uses therof |
US6413792B1 (en) | 2000-04-24 | 2002-07-02 | Eagle Research Development, Llc | Ultra-fast nucleic acid sequencing device and a method for making and using the same |
US6311627B1 (en) | 2000-05-12 | 2001-11-06 | John D. Draper | Article wrapping table assembly |
US6264987B1 (en) | 2000-05-19 | 2001-07-24 | Alkermes Controlled Therapeutics Inc. Ii | Method for preparing microparticles having a selected polymer molecular weight |
US6375981B1 (en) | 2000-06-01 | 2002-04-23 | A. E. Staley Manufacturing Co. | Modified starch as a replacement for gelatin in soft gel films and capsules |
EP1289849A4 (en) | 2000-06-16 | 2004-03-17 | Dlh Inc | FIRST AID KIT |
US6394306B1 (en) | 2000-06-23 | 2002-05-28 | Delsys Pharmaceutical Corp. | Medication dispenser for dispensing flat dosage forms |
DE10034491A1 (de) | 2000-07-15 | 2002-01-24 | Scs Skin Care Systems Gmbh | Folien-Dermatika |
EP1301186A1 (en) | 2000-07-19 | 2003-04-16 | Lavipharm Laboratories, Inc. | Sildenafil citrate solid dispersions having high water solubility |
CA2416257A1 (en) | 2000-07-21 | 2002-01-31 | Union Carbide Chemicals & Plastics Technology Corporation | Compositions and films for capsule manufacture |
ES2185452B2 (es) | 2000-08-01 | 2004-03-16 | Cinfa S A Lab | Composicion farmaceutica de fluoxetina en comprimido dispersable recubierto y su proceso de fabricacion. |
US6572908B2 (en) | 2000-09-05 | 2003-06-03 | Mionix Corporation | Highly acidic metalated organic acid as a food additive |
US6986920B2 (en) | 2000-10-23 | 2006-01-17 | Sealstrip Corporation | Composite web for making gusseted packages |
US6565873B1 (en) | 2000-10-25 | 2003-05-20 | Salvona Llc | Biodegradable bioadhesive controlled release system of nano-particles for oral care products |
US6454788B1 (en) | 2000-11-07 | 2002-09-24 | Wesley Scott Ashton | Method and apparatus for oral hydration and medication administration using a pacifier apparatus |
US6932861B2 (en) | 2000-11-28 | 2005-08-23 | Fmc Corporation | Edible PGA coating composition |
US20020131990A1 (en) | 2000-11-30 | 2002-09-19 | Barkalow David G. | Pullulan free edible film compositions and methods of making the same |
US20020119196A1 (en) | 2000-12-21 | 2002-08-29 | Narendra Parikh | Texture masked particles containing an active ingredient |
IN190699B (zh) | 2001-02-02 | 2003-08-16 | Sun Pharmaceutical Ind Ltd | |
IL157320A0 (en) | 2001-02-08 | 2004-02-19 | Pharmacia Corp | Rapid-onset medicament for the treatment of sexual dysfunction |
JP2004525110A (ja) | 2001-02-16 | 2004-08-19 | 清水製薬株式会社 | ムコ多糖類製剤およびその製造法 |
EP1367999A4 (en) | 2001-02-16 | 2007-04-18 | Lavipharm Lab Inc | WATER-SOLUBLE AND PALATABLE COMPLEXES |
US6419906B1 (en) | 2001-03-12 | 2002-07-16 | Colgate Palmolive Company | Strip for whitening tooth surfaces |
US6776157B2 (en) | 2001-03-14 | 2004-08-17 | The Regents Of The University Of Michigan | Medical pacifier and method for use thereof |
FR2822442B1 (fr) | 2001-03-22 | 2003-08-15 | Danisco Flexible France | Feuille d'emballage comportant une bande d'ouverture et emballage la comportant |
US20020170567A1 (en) | 2001-04-06 | 2002-11-21 | John Rizzotto | Chewable flavor delivery system |
US6503532B1 (en) | 2001-04-13 | 2003-01-07 | Murty Pharmaceuticals, Inc. | Pharmaceutical composition containing tetrahydrocannabinol and a transdermal/transcutaneous delivery method thereof |
US6668839B2 (en) | 2001-05-01 | 2003-12-30 | Jonnie R. Williams | Smokeless tobacco product |
US20040137458A1 (en) | 2001-05-03 | 2004-07-15 | Christian Archambault | Molecular tag code for monitoring a product and process using same |
EP1404269B1 (en) | 2001-05-16 | 2007-10-24 | Susanna Elizabeth Chalmers | Wound dressings and wound treatment compositions |
US6730319B2 (en) | 2001-06-06 | 2004-05-04 | Hoffmann-La Roche Inc. | Pharmaceutical compositions having depressed melting points |
US6962715B2 (en) | 2001-10-24 | 2005-11-08 | Hewlett-Packard Development Company, L.P. | Method and dosage form for dispensing a bioactive substance |
US6660292B2 (en) | 2001-06-19 | 2003-12-09 | Hf Flavoring Technology Llp | Rapidly disintegrating flavored film for precooked foods |
US7943173B2 (en) | 2001-07-18 | 2011-05-17 | Purdue Pharma L.P. | Pharmaceutical combinations of oxycodone and naloxone |
EP1453488B1 (en) | 2001-07-30 | 2009-10-07 | Wm. Wrigley Jr. Company | Improved edible film formulations containing maltodextrin |
US6656493B2 (en) | 2001-07-30 | 2003-12-02 | Wm. Wrigley Jr. Company | Edible film formulations containing maltodextrin |
US6419903B1 (en) | 2001-08-20 | 2002-07-16 | Colgate Palmolive Company | Breath freshening film |
AU2002341959A1 (en) | 2001-10-04 | 2003-04-14 | Case Western Reserve University | Drug delivery devices and methods |
US8603514B2 (en) | 2002-04-11 | 2013-12-10 | Monosol Rx, Llc | Uniform films for rapid dissolve dosage form incorporating taste-masking compositions |
US20070281003A1 (en) | 2001-10-12 | 2007-12-06 | Fuisz Richard C | Polymer-Based Films and Drug Delivery Systems Made Therefrom |
US7666337B2 (en) | 2002-04-11 | 2010-02-23 | Monosol Rx, Llc | Polyethylene oxide-based films and drug delivery systems made therefrom |
AU2002362772B2 (en) | 2001-10-12 | 2007-09-06 | Aquestive Therapeutics, Inc. | Uniform films for rapid dissolve dosage form incorporating taste-masking compositions |
US8765167B2 (en) | 2001-10-12 | 2014-07-01 | Monosol Rx, Llc | Uniform films for rapid-dissolve dosage form incorporating anti-tacking compositions |
EP2351557B1 (en) | 2001-10-12 | 2019-04-17 | Aquestive Therapeutics, Inc. | Thin film with non-self-aggregating uniform heterogeneity, process for ther production and drug delivery systems made therefrom |
US7357891B2 (en) | 2001-10-12 | 2008-04-15 | Monosol Rx, Llc | Process for making an ingestible film |
US20060039958A1 (en) | 2003-05-28 | 2006-02-23 | Monosolrx, Llc. | Multi-layer films having uniform content |
US7425292B2 (en) | 2001-10-12 | 2008-09-16 | Monosol Rx, Llc | Thin film with non-self-aggregating uniform heterogeneity and drug delivery systems made therefrom |
ATE536869T1 (de) | 2001-10-12 | 2011-12-15 | Monosolrx Llc | Auf glucan-film basierte wirkstoffverabreichungssysteme |
US8663687B2 (en) | 2001-10-12 | 2014-03-04 | Monosol Rx, Llc | Film compositions for delivery of actives |
EP1448222A4 (en) | 2001-10-19 | 2006-05-17 | Lilly Co Eli | BIPHASIC MIXTURES OF GLP-1 AND INSULIN |
CN1585650A (zh) | 2001-11-16 | 2005-02-23 | 吉万奥丹股份有限公司 | 可食性薄膜 |
US7464819B2 (en) | 2001-11-30 | 2008-12-16 | West Pharmaceutical Services, Inc. | Child-resistant container |
DE10159746B4 (de) | 2001-12-05 | 2006-05-18 | Lts Lohmann Therapie-Systeme Ag | Spendevorrichtung für flächenförmige Darreichungsformen |
US20030121932A1 (en) | 2001-12-27 | 2003-07-03 | Krystyna Wajda | Apparatus for dispensing flat articles |
JP4616556B2 (ja) | 2002-01-16 | 2011-01-19 | インターベツト・インターナシヨナル・ベー・ベー | ポリ酒石酸エステル組成物 |
US20030140760A1 (en) | 2002-01-25 | 2003-07-31 | Steven Bory | Film cutter |
US20030143195A1 (en) * | 2002-01-30 | 2003-07-31 | Pinsker Judy Senior | Use of histamine as a drug delivery enhancing compound for use in transmucosal or transdermal delivery |
US20050003048A1 (en) | 2002-02-11 | 2005-01-06 | Edizone, Lc | Electrolyte-containing orally soluble films |
US7993674B2 (en) | 2002-02-13 | 2011-08-09 | Weibel Michael K | Drug dose-form and method of manufacture |
DE60301809T2 (de) | 2002-02-13 | 2006-07-13 | Daiwa Gravure Co., Ltd., Nagoya | Gewürzmittelbeuteln |
US6726054B2 (en) | 2002-03-29 | 2004-04-27 | Tapemark | Dispenser package arrangement and methods |
AU2003224890A1 (en) | 2002-04-08 | 2003-10-27 | Lavipharm Laboratories Inc. | Drug-complex microparticles and methods of making/using same |
US8017150B2 (en) | 2002-04-11 | 2011-09-13 | Monosol Rx, Llc | Polyethylene oxide-based films and drug delivery systems made therefrom |
JP2003312688A (ja) | 2002-04-18 | 2003-11-06 | Okayama Taiho Pharmaceutical Co Ltd | 包装袋 |
KR20110004921A (ko) | 2002-05-16 | 2011-01-14 | 규큐 야쿠힝 고교 가부시키가이샤 | 속용성 필름형상 제제 |
ITPD20020141A1 (it) | 2002-05-28 | 2003-11-28 | Bp Europack Spa | Contenitore flessibile ad apertura agevolata e richiudibile |
AU2003240824B9 (en) | 2002-05-31 | 2008-09-25 | University Of Mississippi | Transmucosal delivery of cannabinoids |
JP3901592B2 (ja) | 2002-06-24 | 2007-04-04 | 株式会社フジキカイ | 再封性包装袋と製袋充填機 |
US7093736B2 (en) | 2002-07-11 | 2006-08-22 | West Pharmaceutical Services, Inc. | Alarmed tablet dispenser |
EP1542903B1 (en) | 2002-07-22 | 2015-05-20 | MonoSolRX, LLC | Packaging and dispensing of rapid dissolve dosage form |
GB2391385A (en) | 2002-07-26 | 2004-02-04 | Seiko Epson Corp | Patterning method by forming indent region to control spreading of liquid material deposited onto substrate |
US7241411B2 (en) | 2002-08-23 | 2007-07-10 | Acupac Packaging, Inc. | Thin film strips |
US6824829B2 (en) | 2002-08-23 | 2004-11-30 | Acupac Packaging, Inc. | Process for manufacturing thin film strips |
US20040058457A1 (en) | 2002-08-29 | 2004-03-25 | Xueying Huang | Functionalized nanoparticles |
US6752824B2 (en) | 2002-08-29 | 2004-06-22 | Eric A. Yancy | Ready-to-use sensory diversion device |
US6845282B2 (en) | 2002-09-04 | 2005-01-18 | The Procter & Gamble Company | Method of controlling tension in a web |
US20040120991A1 (en) | 2002-09-07 | 2004-06-24 | Mars Incorporated | Edible films having distinct regions |
GB0221493D0 (en) | 2002-09-17 | 2002-10-23 | Glaxo Group Ltd | Method for loading a medicament dispenser with a medicament carrier |
US20040171139A1 (en) | 2002-09-24 | 2004-09-02 | Belcher Angela M. | Fabricated biofilm storage device |
DE10244504A1 (de) | 2002-09-25 | 2004-04-08 | Capsulution Nanoscience Ag | Schnellfreisetzende Darreichungsform mit schwerlöslichem Wirkstoff |
JP4608836B2 (ja) | 2002-10-18 | 2011-01-12 | 凸版印刷株式会社 | エンボス付き包装袋 |
US6984439B2 (en) | 2002-11-12 | 2006-01-10 | Kimberly-Clark Worldwide, Inc. | Responsive film with corrugated microlayers having improved properties |
CA2505833A1 (en) | 2002-11-14 | 2004-06-03 | Innozen, Inc. | Edible film for relief of cough or symptoms associated with pharyngitis |
US20040191302A1 (en) | 2003-03-28 | 2004-09-30 | Davidson Robert S. | Method and apparatus for minimizing heat, moisture, and shear damage to medicants and other compositions during incorporation of same with edible films |
US20060035008A1 (en) | 2002-11-14 | 2006-02-16 | Givaudan Sa | Edible film containing food acid |
US8999372B2 (en) | 2002-11-14 | 2015-04-07 | Cure Pharmaceutical Corporation | Methods for modulating dissolution, bioavailability, bioequivalence and drug delivery profile of thin film drug delivery systems, controlled-release thin film dosage formats, and methods for their manufacture and use |
US20040111275A1 (en) | 2002-11-15 | 2004-06-10 | Kroll David B. | Methods for marketing and generating revenue from edible thin films |
US20040096569A1 (en) * | 2002-11-15 | 2004-05-20 | Barkalow David G. | Edible film products and methods of making same |
US6772037B2 (en) | 2002-11-26 | 2004-08-03 | Honeywell International Inc. | Constraint based material trimming controller |
US20040241242A1 (en) | 2002-12-06 | 2004-12-02 | Kosmos Pharma | Thin film delivery systems for volatile decongestants |
CA2509382A1 (en) | 2002-12-17 | 2004-07-08 | Todd C. Zion | Stimuli-responsive systems for controlled drug delivery |
US7166575B2 (en) * | 2002-12-17 | 2007-01-23 | Nastech Pharmaceutical Company Inc. | Compositions and methods for enhanced mucosal delivery of peptide YY and methods for treating and preventing obesity |
US6669929B1 (en) | 2002-12-30 | 2003-12-30 | Colgate Palmolive Company | Dentifrice containing functional film flakes |
US20040208931A1 (en) | 2002-12-30 | 2004-10-21 | Friend David R | Fast dissolving films for oral administration of drugs |
JP2004222663A (ja) | 2003-01-27 | 2004-08-12 | Ni Corportion Co Ltd | 可食性フィルム |
US20040219109A1 (en) | 2003-03-10 | 2004-11-04 | Hatch Edwin Burton | Printing identification of incorporated medications onto medicated chewing gums, medicated candies, and other medicated edible products |
CN1764434A (zh) | 2003-03-26 | 2006-04-26 | 宝洁公司 | 含有纤维素成膜聚合物的可迅速溶解的可食用薄膜组合物 |
US6708826B1 (en) | 2003-04-30 | 2004-03-23 | Warner-Lambert Company, Llc | Packaged supply of individual doses of a personal care product |
AU2004319243B2 (en) | 2003-05-28 | 2010-06-03 | Aquestive Therapeutics, Inc. | Polyethylene oxide-based films and drug delivery systems made therefrom |
US20050035133A1 (en) | 2003-05-29 | 2005-02-17 | Gerulski Kristopher W. | Method and apparatus for dispensing a sheet materials |
GB0312419D0 (en) | 2003-05-30 | 2003-07-02 | Boots Healthcare Int Ltd | Use of a compound in the treatment of sleep disorders and the like, in providing refreshedness on waking and a method for the treatment of grogginess |
FR2856385B1 (fr) | 2003-06-20 | 2008-03-07 | Mars Inc | Pochon souple avec ligne de predecoupe |
US20050011776A1 (en) | 2003-07-14 | 2005-01-20 | Nagel Richard R. | Easy access credit card holder |
US7591801B2 (en) | 2004-02-26 | 2009-09-22 | Dexcom, Inc. | Integrated delivery device for continuous glucose sensor |
US7390503B1 (en) | 2003-08-22 | 2008-06-24 | Barr Laboratories, Inc. | Ondansetron orally disintegrating tablets |
US9149440B2 (en) | 2003-09-02 | 2015-10-06 | University Of South Florida | Nanoparticles for drug-delivery |
JP2007514518A (ja) | 2003-10-02 | 2007-06-07 | トラスティーズ オブ スティーヴンス インスティチュート オブ テクノロジー | 水素結合によって結合した多層中性ポリマーフィルムのカプセル |
US20050075432A1 (en) | 2003-10-07 | 2005-04-07 | Verrall Andrew P. | Acidulent film and method of making same |
US7470397B2 (en) | 2003-10-24 | 2008-12-30 | Adhesives Research, Inc. | Disintegratable films for diagnostic devices |
US7040503B2 (en) | 2003-10-29 | 2006-05-09 | Richard A. Leichter | Dispenser |
SE0302924D0 (sv) | 2003-11-05 | 2003-11-05 | Camurus Ab | Pharmaceutical composition having a cationic excipient |
EP1694303A1 (en) | 2003-12-15 | 2006-08-30 | Council Of Scientific And Industrial Research | Taste masked pharmaceutical composition comprising ph sensitive polymer |
US20050191349A1 (en) | 2003-12-31 | 2005-09-01 | Garth Boehm | Galantamine formulations |
US20050170138A1 (en) | 2004-01-20 | 2005-08-04 | Berry Craig J. | Laminated thin film with increased dosage loading and improved physical film properties and method for manufacture |
FR2865130B1 (fr) | 2004-01-21 | 2007-10-05 | Oreal | Film anhydre pour le maquillage ou le soin des levres. |
DE202004003781U1 (de) | 2004-03-11 | 2004-05-13 | Klocke Verpackungs-Service Gmbh | Kindersichere Verpackung |
PT2319500E (pt) | 2004-03-12 | 2013-01-23 | Biodel Inc | Composições de distribuição de fármacos de actuação rápida |
US20080248999A1 (en) | 2007-04-04 | 2008-10-09 | Biodel Inc. | Amylin formulations |
US7127358B2 (en) | 2004-03-30 | 2006-10-24 | Tokyo Electron Limited | Method and system for run-to-run control |
MXPA06011820A (es) | 2004-04-16 | 2006-12-15 | Santarus Inc | Combinacion de inhibidor de bomba de proton, agente regulador del ph y agente procinetico. |
US20050232977A1 (en) | 2004-04-20 | 2005-10-20 | Khan Sadath U | Metered mixing technology for improved taste masking |
WO2005102863A1 (en) | 2004-04-21 | 2005-11-03 | Ashok Chaturvedi | An improved sachet pouch |
JP2007533697A (ja) | 2004-04-22 | 2007-11-22 | デュオコート エービー | グルココルチコイド救急治療用の医薬組成物 |
DE602005015506D1 (de) | 2004-04-28 | 2009-09-03 | Shinetsu Chemical Co | Filmzubereitung und Verfahren zu deren Herstelllung |
US20050266085A1 (en) | 2004-05-28 | 2005-12-01 | Warner Kevin S | Gelled emulsion and microemulsion formulations for dermal drug delivery |
WO2006004480A1 (en) | 2004-07-02 | 2006-01-12 | Radi Medical Systems Ab | Smokeless toabacco product |
US20080300173A1 (en) | 2004-07-13 | 2008-12-04 | Defrees Shawn | Branched Peg Remodeling and Glycosylation of Glucagon-Like Peptides-1 [Glp-1] |
US20060083786A1 (en) | 2004-07-29 | 2006-04-20 | Glenmark Pharmaceuticals Limited | Taste masking pharmaceutical composition containing levocetirizine |
US7607834B2 (en) | 2004-08-02 | 2009-10-27 | R.P. Scherer Technologies, Inc. | Peelable pouch containing a single or multiple dosage forms and process of making same |
US20110257096A1 (en) | 2004-08-25 | 2011-10-20 | Aegis Therapeutics, Inc. | Compositions for drug administration |
DE102004047447B4 (de) | 2004-09-30 | 2008-01-03 | Lts Lohmann Therapie-Systeme Ag | Peelfähige, kindesichere Verpackung für flache, biegsame Objekte, Verwendung dieser Verpackungen und Verfahren zum Verpacken von flachen, biegsamen Objekten |
EP1811980B1 (en) | 2004-09-30 | 2011-06-01 | The Hershey Company | Sealed, edible film strip packets and methods of making and using them |
EP2335921A1 (en) | 2004-09-30 | 2011-06-22 | MonoSolRX, LLC | Multi-layer films |
US20060071057A1 (en) | 2004-09-30 | 2006-04-06 | Kimberly-Clark Worldwide, Inc. | Frangible seal for packaging |
DE102004047445B4 (de) | 2004-09-30 | 2007-05-31 | Lts Lohmann Therapie-Systeme Ag | Nichtwiederverschließbare Verpackung für gesundheitsgefährdende Erzeugnisse, Verwendung der Verpackung, sowie Verfahren zu deren Herstellung |
AU2005291058B2 (en) | 2004-10-01 | 2011-09-29 | Midatech Limited | Nanoparticles comprising antigens and adjuvants and immunogenic structure |
US20060073173A1 (en) | 2004-10-04 | 2006-04-06 | Maria Banach | Large-scale manufacturing process for the production of pharmaceutical compositions |
US20090029074A1 (en) | 2004-10-11 | 2009-01-29 | John Sasine | Method and process for collecting and processing recyclable waste |
US20060104910A1 (en) | 2004-11-15 | 2006-05-18 | Keith Lerner | Over dosage indicating medicated film strip |
JP2006159385A (ja) | 2004-12-10 | 2006-06-22 | Horizon International Inc | 厚み検出器付断裁機 |
CA2491007A1 (en) | 2004-12-23 | 2006-06-23 | Thomas D. Intini | Package for dispensing individual portions |
US20060182796A1 (en) | 2005-02-03 | 2006-08-17 | Abrika Pharmaceuticals, Inc. | Taste masked pharmaceutical compositions |
CN101128369A (zh) | 2005-02-14 | 2008-02-20 | 麦克内尔-Ppc股份有限公司 | 用于个人护理产品的包装 |
US20060198885A1 (en) | 2005-02-22 | 2006-09-07 | Sun Pharmaceutical Industries Ltd. | Oral pharmaceutical composition |
US7714086B2 (en) | 2005-02-23 | 2010-05-11 | The Procter & Gamble Company | Polyvinyl alcohol co-polymer, and water-soluble films and pouches formed therefrom |
DE202005004916U1 (de) | 2005-03-23 | 2005-06-16 | Monolith GmbH Bürosysteme | Schneidgerät |
US20060215941A1 (en) | 2005-03-24 | 2006-09-28 | Allen Golbert | Twin support aperture side tear bag pack |
US20060246141A1 (en) | 2005-04-12 | 2006-11-02 | Elan Pharma International, Limited | Nanoparticulate lipase inhibitor formulations |
EP1877094A1 (en) | 2005-05-03 | 2008-01-16 | Innozen, Inc. | Edible film for transmucosal delivery of nutritional supplements |
CA2607780A1 (en) | 2005-05-04 | 2006-11-09 | Pfizer Limited | Purine derivatives |
US20060281775A1 (en) | 2005-06-14 | 2006-12-14 | Applied Pharmacy Services, Inc. | Two-component pharmaceutical composition for the treatment of pain |
US20060286108A1 (en) | 2005-06-16 | 2006-12-21 | Bell Katherine A | Topical compositions for the treatment of chronic wounds |
AR055973A1 (es) | 2005-06-17 | 2007-09-12 | Novartis Ag | Contenedor para suministrar bolsas individuales |
US7665896B1 (en) | 2005-06-23 | 2010-02-23 | Circle Back, Inc. | Plastic bag to facilitate evacuation prior to sealing |
NZ561375A (en) | 2005-06-27 | 2011-06-30 | Biovail Lab Int Srl | Bupropion hydrobromide, and crystalline forms, compositions, and uses of this compound |
EP1954240A2 (en) | 2005-07-15 | 2008-08-13 | Bayer Schering Pharma Aktiengesellschaft | Drospirenone containing transdermal drug delivery devices and methods of delivery thereof |
US9034380B2 (en) | 2005-08-04 | 2015-05-19 | Midatech Ltd. | Nanoparticles comprising antibacterial ligands |
US20070098746A1 (en) | 2005-11-02 | 2007-05-03 | Nichols William M | Multi-layered coating technology for taste masking |
WO2007078192A1 (en) | 2005-12-06 | 2007-07-12 | Innospense Capital B.V. | Container, dispenser, and method for dispensing a strip of interconnected, individually packed objects |
JP2009518405A (ja) | 2005-12-06 | 2009-05-07 | モノソル アールエックス リミテッド ライアビリティ カンパニー | 活性物質の送達のための局所フィルム組成物 |
US9522188B2 (en) | 2005-12-13 | 2016-12-20 | Biodelivery Sciences International, Inc. | Abuse resistant transmucosal drug delivery device |
US20070170196A1 (en) | 2005-12-15 | 2007-07-26 | Autronic Plastics, Inc. | Package for storing and dispensing foil protected edible film strips |
US8038008B2 (en) | 2005-12-21 | 2011-10-18 | Watson Laboratories, Inc. | Medicament dispenser and associated methods |
WO2007073702A2 (es) | 2005-12-29 | 2007-07-05 | Osmotica Corp. | Comprimido multicapa con combinación de triple liberación |
JP4456572B2 (ja) | 2006-03-06 | 2010-04-28 | 大日本印刷株式会社 | 易開封袋 |
US20070205127A1 (en) | 2006-03-06 | 2007-09-06 | R.P. Scherer Technologies, Inc. | Peelable pouch containing a single film dosage and process of making same |
US20070231368A1 (en) | 2006-03-30 | 2007-10-04 | Enanta Pharmaceuticals, Inc. | Pharmaceutical formulations of 6-11 bicyclic macrolide derivative known as edp-182 and methods for preparation thereof |
AU2007242572B2 (en) | 2006-04-13 | 2011-11-24 | Midatech Limited | Nanoparticles containing three various ligands for providing immune responses against infectious agents |
IL175338A0 (en) | 2006-05-01 | 2006-09-05 | Biota Ltd | Orally administrable films and preparation thereof |
ITPD20060173A1 (it) | 2006-05-04 | 2007-11-05 | Ferdinando Baldan | Nuovo dispenser per bustine e/o confezioni di zucchero e/o di dolcificante, con dispositivi di taglio, per l'apertura delle bustine, e contenitore/i di raccolta dei rifiuti |
JP5265527B2 (ja) | 2006-05-19 | 2013-08-14 | モノソル・アールエックス・エルエルシー | ディスペンサーアセンブリおよびポーチカッター |
TW200816985A (en) * | 2006-06-05 | 2008-04-16 | Verus Pharmaceuticals Inc | Methods for buccal, lingual or sublingual dosing regimens of epinephrine for the treatment of allergic emergencies |
JP2008011194A (ja) | 2006-06-29 | 2008-01-17 | Fujifilm Corp | 画像処理装置 |
RS54764B1 (sr) | 2006-07-21 | 2016-10-31 | Biodelivery Sciences Int Inc | Sredstvo za transmukozalnu isporuku sa povećanim nakupljanjem |
EP1897543A1 (en) | 2006-08-30 | 2008-03-12 | Euro-Celtique S.A. | Buprenorphine- wafer for drug substitution therapy |
JP4739452B2 (ja) | 2006-09-20 | 2011-08-03 | モノソル アールエックス リミテッド ライアビリティ カンパニー | 発泡を減じる風味付与剤を含む喫食可能な水溶性フィルム |
JP4805778B2 (ja) | 2006-09-27 | 2011-11-02 | 富士フイルム株式会社 | 包装方法及び装置 |
AU2007305271A1 (en) | 2006-09-29 | 2008-04-10 | Monosol Rx Llc | Film embedded packaging and method of making same |
BRPI0719840A2 (pt) | 2006-10-02 | 2014-11-25 | Labtec Gmbh | Formas de dosagem de películas não-mucoadesiva |
US20100015128A1 (en) | 2006-10-03 | 2010-01-21 | University Of Southern California | GRP78 as a Predictor of Responsiveness to Therapeutic Agents |
CN101616660A (zh) | 2007-01-12 | 2009-12-30 | 莫诺索尔克斯有限公司 | 高剂量膜组合物及其制备方法 |
GB2447016A (en) | 2007-03-01 | 2008-09-03 | Reckitt Benckiser Healthcare | Buprenorphine/naloxone compositions |
US20090014491A1 (en) | 2007-03-02 | 2009-01-15 | Monosol Rx, Llc. | Packet structure, such as for a film strip |
US8568777B2 (en) | 2007-03-30 | 2013-10-29 | Monosol Rx, Llc | Packaged film dosage unit containing a complexate |
US8181433B2 (en) | 2007-04-27 | 2012-05-22 | Land O'lakes, Inc. | Method of lap sealing a molten cheese product with non-wax film |
US20090004254A1 (en) | 2007-06-19 | 2009-01-01 | Todd Maibach | Film comprising active drugs |
US20090009332A1 (en) | 2007-07-03 | 2009-01-08 | Endotronix, Inc. | System and method for monitoring ingested medication via rf wireless telemetry |
GB0717054D0 (en) | 2007-09-01 | 2007-10-17 | Eastman Kodak Co | Patterning method |
DE102007044829B4 (de) | 2007-09-18 | 2011-05-26 | Jenoptik Automatisierungstechnik Gmbh | Verpackungsbeutel mit Aufreißhilfe |
GB0719095D0 (en) | 2007-10-01 | 2007-11-07 | Bioprogress Technology Ltd | Indelibly marked polymeric films |
US20090146336A1 (en) | 2007-10-02 | 2009-06-11 | R Tape Corporation | Process for making shrink films with embossed optical or holographic devices |
US8298583B2 (en) | 2007-10-19 | 2012-10-30 | Monosol Rx, Llc | Film delivery system for tetrahydrolipstatin |
EP2214478A1 (en) | 2007-10-19 | 2010-08-11 | Innozen, Inc. | Composition for administering an active ingredient and method for making and using the same |
US7694617B2 (en) | 2008-01-24 | 2010-04-13 | Henry Habra | Gift wrap paper cutter |
BRPI0906648A2 (pt) | 2008-01-31 | 2019-11-19 | Mcneil Ppc Inc | tiras de filme comestível para liberação imediata de ingredientes ativos |
US8387115B2 (en) | 2008-02-21 | 2013-02-26 | Syracuse University | Active access control system and method |
CA2657689A1 (en) | 2008-03-27 | 2009-09-27 | Bruce D. Detwiler | Tearable packages for pharmaceutical product and method |
CN102056578A (zh) | 2008-06-23 | 2011-05-11 | 生物递送科学国际公司 | 多向粘膜给药装置及使用方法 |
CA2749564C (en) | 2009-01-13 | 2016-11-15 | Monosolrx Llc | Unit assembly for multiple film dosages, apparatus, and methods |
US20120058158A1 (en) * | 2009-04-23 | 2012-03-08 | Londonpharma Ltd. | Sublingual Pharmaceutical Composition Comprising a Neutral Oil |
US20100297232A1 (en) | 2009-05-19 | 2010-11-25 | Monosol Rx, Llc | Ondansetron film compositions |
EP2305310A1 (en) | 2009-09-25 | 2011-04-06 | Asociación Centro de Investigación Cooperativa en Biomateriales - CIC biomaGUNE | Gold -coated magnetic glyconanoparticles functionalised with proteins for use as diagnostic and therapeutic agents |
US20110192863A1 (en) * | 2009-12-31 | 2011-08-11 | Paul Leslie Barrass | Ingestible Tablet Dispensers And Methods Of Dispensing Tablets |
IE20100174A1 (en) | 2010-03-25 | 2012-02-29 | Trinity College Dublin | Transdermal administration of peptides |
US9572773B2 (en) * | 2010-04-26 | 2017-02-21 | Novartis A.G. | Layered drug delivery device |
AU2011265294B2 (en) * | 2010-06-10 | 2015-01-22 | Aquestive Therapeutics, Inc. | Nanoparticle film delivery systems |
CA2815568C (en) * | 2010-09-23 | 2018-10-09 | Monosolrx Llc | Method and system for forming a pharmaceutical product directly onto a packaging surface |
JP5147140B2 (ja) | 2010-11-25 | 2013-02-20 | サミー株式会社 | 弾球遊技機 |
WO2012070028A1 (en) | 2010-11-26 | 2012-05-31 | University Of The Witwatersrand, Johannesburg | A pharmaceutical dosage form |
US8241661B1 (en) * | 2011-06-24 | 2012-08-14 | Fuisz Richard C | Biocompatible film with variable cross-sectional properties |
FR3013589B1 (fr) | 2013-11-28 | 2017-03-31 | Soc D'exploitation De Produits Pour Les Ind Chimiques Seppic | Composition d'alkyl polyglucosides et d'acides gras cationisees |
CN108697803A (zh) | 2015-10-29 | 2018-10-23 | 索卢贝斯特有限公司 | 透粘膜给药的药物组合物 |
CA3022797A1 (en) | 2016-05-05 | 2017-11-09 | Aquestive Therapeutics, Inc. | Pharmaceutical compositions with enhanced permeation |
JP2019519487A (ja) | 2016-05-05 | 2019-07-11 | アクエスティブ セラピューティクス インコーポレイテッド | 送達増強エピネフリン組成物 |
US20190022023A1 (en) | 2016-05-05 | 2019-01-24 | Aquestive Therapeutics, Inc. | Enhanced delivery epinephrine and prodrug compositions |
KR20200060457A (ko) | 2017-09-27 | 2020-05-29 | 어퀘스티브 테라퓨틱스, 아이엔씨. | 강화된 투과를 가지는 약물학적 조성물 |
CA3076816A1 (en) | 2017-09-27 | 2019-04-04 | Aquestive Therapeutics, Inc. | Enhanced delivery epinephrine and prodrug compositions |
-
2017
- 2017-05-04 JP JP2018558224A patent/JP2019519487A/ja active Pending
- 2017-05-04 KR KR1020187035240A patent/KR20190005199A/ko not_active IP Right Cessation
- 2017-05-04 WO PCT/US2017/031167 patent/WO2017192921A1/en unknown
- 2017-05-04 BR BR112018072539-0A patent/BR112018072539A2/pt active Search and Examination
- 2017-05-04 EP EP17723616.3A patent/EP3452023A1/en active Pending
- 2017-05-04 CA CA3022840A patent/CA3022840A1/en active Pending
- 2017-05-04 CN CN201780037587.5A patent/CN109310646A/zh active Pending
- 2017-05-04 US US15/587,364 patent/US11191737B2/en active Active
- 2017-05-04 KR KR1020237027814A patent/KR20230137362A/ko not_active Application Discontinuation
-
2018
- 2018-11-04 IL IL262750A patent/IL262750B/en unknown
-
2022
- 2022-06-08 US US17/835,442 patent/US20230138361A1/en active Pending
- 2022-12-28 JP JP2022211123A patent/JP2023052143A/ja active Pending
Patent Citations (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20030044446A1 (en) * | 2001-08-16 | 2003-03-06 | Mucoadhesive Erodible Drug Delivery Device For Controlled Admn. Of Pharmaceuticals & Other Acti | Mucoadhesive erodible drug delivery device for controlled administration of pharmaceuticals and other active compounds |
CN1777411A (zh) * | 2003-02-24 | 2006-05-24 | 药品生产公司 | 经粘膜药物递送系统 |
US20070202163A1 (en) * | 2005-09-09 | 2007-08-30 | Mutasem Rawas-Qalaji | Fast-disintegrating epinephrine tablets for buccal or sublingual administration |
CN101938991A (zh) * | 2007-12-07 | 2011-01-05 | 先灵-普劳健康护理产品公司 | 用于跨粘膜吸收的苯肾上腺素的药物制剂和组合物 |
US20140316333A1 (en) * | 2011-10-28 | 2014-10-23 | Sung-Yun Kwon | Dissolving solid solution perforator patch for migraine treatment |
Cited By (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN111465391A (zh) * | 2017-09-27 | 2020-07-28 | 阿奎斯蒂弗医疗股份有限公司 | 具有增强的递送的肾上腺素和前药的组合物 |
EP4302751A1 (en) * | 2022-07-07 | 2024-01-10 | LTS Lohmann Therapie-Systeme AG | Oral thin films with low water activity |
WO2024008954A1 (en) * | 2022-07-07 | 2024-01-11 | Lts Lohmann Therapie-Systeme Ag | Oral thin films with low water activity |
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IL262750B (en) | 2022-06-01 |
EP3452023A1 (en) | 2019-03-13 |
US20170348251A1 (en) | 2017-12-07 |
US11191737B2 (en) | 2021-12-07 |
JP2023052143A (ja) | 2023-04-11 |
KR20190005199A (ko) | 2019-01-15 |
JP2019519487A (ja) | 2019-07-11 |
WO2017192921A1 (en) | 2017-11-09 |
KR20230137362A (ko) | 2023-10-04 |
CA3022840A1 (en) | 2017-11-09 |
BR112018072539A2 (pt) | 2019-03-26 |
IL262750A (en) | 2018-12-31 |
US20230138361A1 (en) | 2023-05-04 |
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