CN112770727B - 大麻素的缓速释放配方 - Google Patents
大麻素的缓速释放配方 Download PDFInfo
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- CN112770727B CN112770727B CN201980060980.5A CN201980060980A CN112770727B CN 112770727 B CN112770727 B CN 112770727B CN 201980060980 A CN201980060980 A CN 201980060980A CN 112770727 B CN112770727 B CN 112770727B
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Abstract
用于延长释放一种或多种大麻素的组合物,其中所述组合物包含粒子群。每个颗粒可包含一种或多种大麻素,一种或多种药物释放剂,一种或多种表面活性剂,和核。核可包括多孔珠。一种或多种大麻素可包含A9‑四氢大麻酚,大麻二酚,或其组合物。
Description
交叉引用
本申请要求于2018年7月18日提交的美国临时申请序列号62/700,107的权益,其全部内容通过引用合并于此。
技术领域
本发明涉及用于口服施用一种或多种大麻素的缓释的多颗粒药物递送平台。本发明的药物递送系统实现了目标药代动力学特征,并在胃肠道中提供了均匀的药物分布。为了方便施用和处理,本发明的递送系统可以以胶囊,片剂,散剂或棒状包装的形式施用。
技术背景
大麻素是大麻和大麻烟的植物属,具有许多药用和精神活性,据报道它们可减轻与严重医疗条件有关的多种症状,同时比大多数目前的处方药提供更安全和更少的严重副作用。例如,大麻已被用来对抗与癌症,厌食症,艾滋病,慢性疼痛,肌肉痉挛,青光眼,关节炎,偏头痛和许多其他疾病有关的症状。
大麻素是一类来自大麻植物的多种化学物质,它们作用于大麻素受体,可抑制大脑中神经递质的释放。Δ9-四氢大麻酚(THC)和大麻二酚(CBD)是大麻中发现的两种最突出的大麻素。迄今为止,尽管科学家在大麻中发现了100多种不同的大麻素,但CBD和THC却是迄今为止研究最广泛和了解最多的大麻素。CBD和THC都与人体的内源性大麻素系统相互作用,后者是负责调节多种功能的重要信号系统。
THC是一种源自大麻的精神药物,它作用于人体的大麻素受体上,类似于人体天然产生的化学物质。THC是一种精神活性物质,可激活CB1和CB2受体并影响知觉,情绪,意识,认知和行为。在医学应用中,THC具有止痛和食欲兴奋剂的特性。据报道,THC会产生放松和幸福的状态,诱发睡眠并引起欣快感。这些作用已用于治疗各种健康问题,例如疼痛,炎症,恶心,睡眠呼吸暂停和压力障碍。此外,THC已被证明可抵抗化学疗法,多发性硬化症,青光眼,艾滋病和脊柱损伤的副作用和症状。
当前,只有三种由食品和药物管理局(FDA)批准用于THC的药品: 和和都含有屈大麻酚,这是一种合成的THC,不溶于水,pKA为10.6。可作为剂量强度为2.5mg,5mg和10mg的软明胶胶囊而获得,可作为口服溶液(5mg/ml)而获得。和均适用于治疗与艾滋病患者与体重减轻相关的厌食症,以及治疗对常规止吐疗法没有充分反应的患者的与癌症化学疗法相关的恶心和呕吐。
含有萘比隆,萘比隆是一种化学上类似于THC的合成大麻素。萘比隆为原料,为白色至类白色多晶型结晶粉末。在水性介质中,萘丁酮的溶解度小于0.5mg/L,pH值为1.2至7.0。可以粉末填充的胶囊形式(1mg/胶囊)口服给药,适用于对常规止吐疗法没有充分反应的患者,用于治疗与癌症化学疗法有关的恶心和呕吐。然而,据报道,口服后的效果会持续一段可变且不可预测的时间。例如,停止治疗后,使用引起的不良精神病反应会持续48至72小时。
THC具有持续至2-4小时的作用持续时间,持续4-6小时的精神活性作用以及可在口服给药后持续长达24小时的食欲增加作用。由于作用时间短,口服THC产品反应较差或部分,需要患者每天多次给药。的最大建议剂量为每剂每天15毫克/平方米,每天4至6剂,的建议最大剂量为每剂每天12.6毫克/平方米,每天4至6剂。的最大建议每天剂量为6毫克,每天分3次服用。
CBD是另一种衍生自大麻的有效化学物质,其被患者广泛吸食大麻叶而被吸入。迄今为止,FDA仅批准了(一种含有植物来源的CBD的口服溶液(100mg/ml))用于治疗两岁及以上的与两种罕见和严重形式的癫痫病(Lennox-Gastaut syndrome综合征和Dravet syndrome综合征)相关的癫痫发作。CBD是白色至浅黄色的结晶固体。不溶于水,可溶于有机溶剂。CBD的主要医学应用是对抗严重和慢性疼痛,压力,抑郁,焦虑,癌症,癫痫病,精神分裂症,多发性硬化症,偏头痛,关节炎以及化学疗法的不利影响。的最大推荐维持剂量为每天两次10mg/kg。
如上所述,这些FDA批准的药物全部用于多剂量施用。因此,在本领域中仍然需要含有一种或多种大麻素的缓释药物。与某些速释药物相比,缓释药物制剂可用于减少给药频率,改善患者依从性,降低药物毒性(与高峰接触有关的局部或系统性),减少血液中的药物水平波动,以更统一的药物水平稳定医疗状况,通过长期治疗减少药物积累,由于空间控制而提高某些药物的生物利用度并减少总药物使用量。
如果可以将缓释药物概况应用于THC和CBD的药物组合,则将获得进一步的好处。所有FDA批准的药物均包含合成的THC或CBD,而不是两者的组合。尽管尚无FDA批准的将THC和CBD结合使用的药物,但是对大麻植物配方提取物的口腔粘膜喷雾剂,该提取物包含主要的大麻素THC和CBD以及特定的次要大麻素和其他非大麻素成分。适用于治疗由于多发性硬化症(MS)而引起的中度至重度痉挛的成年患者,这些患者对其他抗痉挛药物没有足够的反应,并且在最初的治疗试验期间表现出与痉挛相关的症状的临床显着改善。在欧洲,加拿大,新西兰和以色列,可通过处方获得但是,还需要多剂量给药-每天最多12次喷雾,两次喷雾之间最少间隔15分钟。
CBD的存在可以平衡THC的激动活性。THC激活大脑中存在的大麻素受体CB1和CB2,这些物质负责THC的精神活性,而CBD通过充当大麻素激动剂的间接拮抗剂来抑制CB1和CB2受体。因此,CBD通过类似THC的大麻素抑制了CB1和CB2受体的激活,从而产生了平衡的效果。
THC和CBD组合使用时,具有抗炎,食欲刺激,止吐,抗惊厥,抗氧化剂,神经保护和抗肿瘤作用。THC和CBD也可用于抵抗癫痫,抑郁,焦虑,精神分裂症,多发性硬化症,偏头痛和关节炎,并减轻癌症,艾滋病和脊柱损伤的症状;所有这些改善了那些使人虚弱的患者的生活质量。
此外,THC和CBD优于其他目前的处方药,因为它们不习惯形成,安全且耐受性良好。目前,由于阿片类药物的养成习惯,约有200万美国人开始依赖或滥用处方止痛药。此外,阿片类药物与过量用药导致死亡的风险较高。在本领域中需要强壮的非习惯性止痛药以及耐受性良好且安全的止痛药,以防止过量服用引起的死亡。THC和CBD都是非习惯性强效止痛药,可替代阿片类药物治疗严重和慢性疼痛。
此外,医用大麻的最普遍的给药方式是吸烟。不幸的是,这种给药方式对肺有不利影响。大麻烟雾比烟草携带更多的焦油和其他微粒物质,并且可能是包括肺癌在内的肺部疾病的原因。吸烟也可能对大麻素的吸收产生负面影响。研究表明,随着参与者滴定THC剂量,吸入时间,保持时间和抽吸间隔时间应归因于受试者间血浆THC浓度的巨大差异,这归因于吸入深度的差异。此外,许多患者可能会发现吸烟无吸引力,而且总体上不健康。因此,对开发其他向患者施用大麻的手段引起了极大的兴趣。
因此,在本领域中,对于单独的或组合的THC和CBD的延长释放剂型,用于治疗多种临床病症仍然存在未满足的需求。如下所述的多颗粒,延长释放的剂型将允许精确的剂量,均匀的药物递送,靶向的药代动力学和方便的给药,所有这些目前尚不可用。
发明内容
本发明提供了包含一种或多种大麻素的多颗粒固体口服剂型。这些剂型可以以胶囊,片剂(常规片剂,口腔崩解片(ODT),自崩解片剂,可咀嚼片剂),小袋,散剂或棒状包装的形式给药于接受者,从而易于给药和处理。系统可包括直径范围可为约30μm至约1500μm或约50μm至约1000μm的颗粒(例如,任何形状的颗粒,颗粒团块,珠子或丸粒),并均匀加载。本发明的多颗粒固体口服剂型可以以提供长达24小时的缓释曲线的方式配制,从而提供每天一次的剂量方案,可以帮助实现更高的患者依从性。还可以配制本发明的剂型以实现靶向的药代动力学特征并提供在胃肠道中的均匀分布。
本发明的一个方面涉及用于缓释一种或更多种大麻素的组合物。在一些实施方案中,组合物可包含颗粒群,其中每个颗粒包含一种或多种大麻素、一种或多种药物释放剂和核。在一些实施方案中,颗粒可包含一种或多种大麻素,一种或多种药物释放剂,核,一种或多种增溶剂和一种或多种表面活性剂。缓释所述组合物可以在至少6小时的时期内或在约12-24小时的时期内释放一种或多种大麻素。一种或多种大麻素可以约1%至约90%w/w或约5%至约50%的量存在于组合物中。
在一些实施方案中,一种或多种大麻素可包含THC,CBD或其组合。
在一些实施方案中,一种或多种药物释放剂可包含一种或多种凝胶形成剂。一种或多种凝胶形成剂可以选自单油酸甘油酯,单硬脂酸甘油酯,豆油,单棕榈硬脂酸丙二醇酯,纤维素基胶凝剂,羧基聚亚甲基,羟丙基纤维素,羟丙基甲基纤维素,羧甲基纤维素,壳聚糖,天然树胶如阿拉伯胶,藻酸盐,角叉菜胶,瓜尔豆胶或其组合。
在一些实施方案中,一种或多种凝胶形成剂与一种或多种表面活性剂的重量比例可以为约10:1至约1:10,或约8:1至约1:8,或约5:1到约1:5。
在一些实施方案中,一种或多种增溶剂可包含油,甘油酯,醇或其组合。油可以选自包括但不限于大麻油和芝麻油的油。
在一些实施例中,核可包括多孔珠,例如中孔二氧化硅珠或多孔可生物降解的玻璃珠。孔体积与粒度的比可以在约0.001至约0.8的范围内。在一些实施方案中,孔可包含一种或多种大麻素和一种或多种药物释放剂。在某些实施方案中,孔可包含一种或多种大麻素,一种或多种增溶剂,一种或多种表面活性剂和一种或多种药物释放剂。
在另外的实施方案中,用于缓释一种或多种大麻素的组合物可包含一群颗粒,其中每个颗粒包含:约1%至约20%w/w的一种或多种大麻素,约5%至一种或多种增溶剂的约15%w/w,一种或多种药物释放剂的约15%至约35%w/w,核的约20%至约45%w/w和约15%至约35%w/w的一种或多种表面活性剂。该组合物可以在至少6小时的时间内释放一种或多种大麻素。
在本发明的另一方面,用于缓释一种或多种大麻素的组合物的任何实施方案可用于在有此需要的受试者中治疗健康问题的方法,,其中健康问题选自疼痛,恶心,睡眠呼吸暂停,压力障碍,炎症,抑郁,焦虑,癫痫,精神分裂症,偏头痛,关节炎,体重减轻,食欲不振及其组合。在一些实施方案中,组合物可以口服施用。在某些实施方案中,在施用入水或放入其他类型的液体饮料中之前,可以将组合物撒在固体,半固体或液体的食物或营养物上。
附图说明
为了更好地理解本发明,请参考以下对本发明实施例的描述以及附图,其中:
图1A和1B显示了使用动态光散射技术(美国Malvern仪器)的粒度分布:普通的Neusilin US2磁珠(图1A)和Neusilin US2磁珠在芝麻油和表面活性剂中装有普罗布考(图1B)。
图2A和2B显示了普通的Neusilin US2磁珠(图2A)和装有普罗布考在芝麻油和表面活性剂中的Neusilin US2磁珠(图2B)的扫描电子显微镜(SEM)图像。
图3A和3B显示了如实施例1中所述的根据本发明的速释参考组合物A-C的溶出曲线(图3A)和实施方案的缓释的实施例组合物A-C的溶出曲线(图3B)。
图4显示了如实施例2中所述的根据本发明的实施方案的缓释的实施例组合物D-H的溶出曲线。
图5A和5B显示了如实施例3中所述的根据本发明的实施方案的速释参考组合物D的溶出曲线(图5A)和缓释实施例组合物I的溶出曲线(图5B)。
图6A和6B显示了如实施例4中所述的根据本发明的实施方案的速释参考组合物E的溶出曲线(图6A)和缓释实施例组合物J的溶出曲线(图6B)。
图7A和7B显示了如实施例5中所述的根据本发明的实施方案的速释参考组合物F的溶出曲线(图7A)和缓释实施例组合物K的溶出曲线(图7B)。
图8A-8F示出了在220x(图8A),1000x(图8B)和1600x(图8C)的放大率下的普通Neusilin US2珠的SEM图像;根据本发明的实施方案,放大倍数为190x(图8D),1600x(图8E)和2200x(图8F)的在芝麻油中装载了THC和CBD的Neusilin US2珠粒的SEM图像。
图9A和9B示出了根据本发明的实施方式的在芝麻油中装载有THC和CBD的普通Neusilin US2珠粒的组合物(图9A)和Neusilin US2珠粒的组合物的粒度分布图(图9B)。
具体实施方式
根据本发明,提供了用于施用一种或更多种大麻素的多颗粒缓释剂型。一方面,一种或多种大麻素包含THC,CBD或其组合。在一些实施例中,一种或多种大麻素可以约1%至约90%w/w或约5%至约50%w/w的量。在某些实施方案中,THC和CBD的最终组成,单独地或一起,可以在约1%至约90%w/w的范围内。
在本发明的实施方案中,组合物可包含一群颗粒,其中每个颗粒包含:一种或多种大麻素,一种或多种药物释放剂和核。在一些实施方案中,组合物可包含一群颗粒,其中每个颗粒包含:一种或多种大麻素,一种或多种药物释放剂,一种或多种增溶剂,一种或多种表面活性剂和核。在某些实施方案中,[一种或多种大麻素+一种或多种药物释放剂+一种或多种增溶剂+一种或多种表面活性剂]与核的重量比可以为约5:1至约1:5,或约3:1至约1:3,或约2:1至约1:1。在另一方面,超过约50%的颗粒的直径可在约30μm至约2000μm之间,或在约50μm至约1000μm之间。在另一方面,颗粒可以以胶囊,片剂或小袋的形式提供。
在本发明的一方面,本发明的各种组合物的实施方案可以用于在有此需要的受试者中治疗健康问题的方法,其中所述健康问题选自疼痛,恶心,睡眠呼吸暂停,压力障碍,炎症,抑郁,焦虑,癫痫,精神分裂症,偏头痛,关节炎,体重减轻,食欲不振及其组合。在一实施方案中,组合物可以口服施用。在另一个实施方案中,在施用之前,可以将组合物撒在固体,半固体食物或营养物上;或撒入水中,或撒入其他类型的液体饮料中。
在一些实施方案中,将一种或多种大麻素溶解在芝麻油中并加载到中孔二氧化硅珠上。药物通过毛细作用装载在珠子的孔中。在一些实施方案中,将药物装载在珠子的孔中,随后将其装载在表面活性剂和形成凝胶的脂质赋形剂中以控制药物的释放。
本发明的组合物
如本文所用,术语“缓释”的特征在于,在延长的时间段内,任选地大于约30分钟,一种或多种大麻素从组合物的颗粒中逐渐释放。在缓释的情况下,控制一种或多种大麻素从颗粒中的释放速率,以便在更长的时间内保持一种或多种大麻素的治疗活性。在本发明的一些实施方案中,组合物可以在约6小时或更长时间内释放大于约40%的一种或多种大麻素。在某些实施方案中,组合物可以在约12小时至约24小时的时间内释放一种或多种大麻素活性剂。
如本文所用,术语“增溶剂”是指增加大麻素的生物利用度的溶解度增强赋形剂。一种或多种增溶剂的目的是获得浓缩,均匀且稳定的溶液,以便以有效方式递送大麻素。用于本发明的一种或多种增溶剂可以包括但不限于油,甘油酯,醇或其组合。该油可以选自大麻油,琉璃苣油,椰子油,棉籽油,大豆油,红花油,向日葵油,蓖麻油,玉米油,橄榄油,棕榈油,花生油,杏仁油,芝麻油。油,菜籽油,薄荷油,罂粟籽油,低芥酸菜子油,棕榈仁油,氢化大豆油,氢化植物油及其组合。甘油酯可以选自由甘油单酸酯,甘油二酸酯,甘油三酸酯及其组合物。该醇可以是一元醇,例如乙醇,甲醇或异丙醇。在一些实施方案中,一种或多种增溶剂可以是水醇混合物。
如本文所用,术语“药物释放剂”涉及控制药物递送以使大麻素以预先设计的方式释放的试剂。结果,药物释放剂有助于大麻素对人体的有效利用率和程度。
在一方面,一种或多种药物释放剂可包含一种或多种基于脂质的凝胶形成剂。可以添加凝胶形成剂以形成可以控制药物从组合物中释放的粘性液晶相。凝胶形成剂通过在源和周围介质之间形成不同粘度的凝胶屏障来延长药物的释放,这可以通过调节组合物中存在的凝胶形成剂的量来优化,和/或在一些实施方案中,通过相对于组合物中表面活性剂的量调节凝胶形成剂的量。
一种或多种凝胶形成剂可以选自甘油单油酸酯(例如Capmul GMO-50;美国AbitecCorp.),单硬脂酸甘油酯(例如GeleolTM单酸甘油酯和双酸甘油酯,嘉法狮(Gattefosse),美国),二硬脂酸甘油酯,聚甘油3-二油酸酯(嘉法狮(Gattefosse),美国),大豆油,丙二醇单棕榈酸酯(例如MonosteolTM;嘉法狮(Gattefosse),美国),纤维素基胶凝剂,羧基多亚甲基(例如卡巴浦尔或卡波姆)),羟丙基纤维素,羟丙基甲基甲基纤维素纤维素,羧甲基纤维素,壳聚糖,天然树胶(例如阿拉伯胶,藻酸盐,角叉菜胶,瓜尔豆胶)及其组合。在某些实施方案中,一种或多种凝胶形成剂可包含甘油单油酸酯。
在其中组合物包含一种或多种凝胶形成剂和一种或多种表面活性剂的实施方案中,一种或多种凝胶形成剂与一种或多种表面活性剂的重量比可以为约10:1至约1:10,或约8:1到约1:8,或约5:1到约1:5。根据某些实施方案,一种或多种凝胶形成剂与一种或多种表面活性剂的重量比例可以为约1:1。在某些实施方案中,可以在有或没有表面活性剂的情况下添加纤维素基和胶基胶凝剂。
如本文所用,术语“核”可指可在其上装载一种或多种大麻素,一种或多种药物释放剂等的载体,并且可从中释放这些组分。在本发明的实施方案中,核可包含二氧化硅珠,可生物降解的玻璃珠或由本领域已知适合于口服施用的任何相容性材料制成的任何其他珠(例如,多孔陶瓷,多孔碳酸钙颗粒,多孔沸石颗粒等)。
核也可以从核的表面延伸的一个或多个核。核可包含一种或多种大麻素和一种或多种药物释放剂,以及在一些实施方案中,一种或多种增溶剂和/或一种或多种表面活性剂。根据一些实施方案,孔体积与核的粒径之比可以在约0.001至约0.8之间。在该范围内,可以配置孔,使得一种或多种药物释放剂位于比一种或多种大麻素更靠近核的表面的孔中。在其中一种或多种增溶剂和一种或多种表面活性剂存在于组合物中的实施方案中,可以配置孔使得一种或多种药物释放剂位于比至少一种或多种大麻素和一种或多种表面活性剂更靠近核的表面的孔中。
根据本发明,考虑到装载能力及其实现自由流动的多颗粒系统的能力来选择核。根据一些实施方案,核包含中孔二氧化硅(例如,XDP 3150(美国,格雷斯),LC150A(美国,格雷斯),US2(日本,富士化学)。二氧化硅珠的颗粒大小,孔体积和比表面积在下表1中给出。
表1.硅珠的物理性质
使用动态光散射技术确定孔体积与粒度的比率,并且对于Neusilin US2磁珠最高。Neusilin US2磁珠的粒径分布如图1A所示,其d90为108μm,具有双峰分布。当将丙丁酚(作为替代活性成分),芝麻油,表面活性剂和形成凝胶的脂质赋形剂与二氧化硅以2:1的比例装载,Neusilin US2珠的粒径分布更改为d90为182μm,具有单峰分布曲线,如图1B所示。图2A和2B中显示了普通和装载的Neusilin US2磁珠的扫描电子显微镜图像。特别是,图2A描绘了普通的Neusilin US2磁珠,图2B描绘了在芝麻油和表面活性剂中载有普罗布考(probucol)(作为替代活性成分)的Neusilin US2磁珠。
硅珠的选择考虑了其在最大药物装载时的流动性。评估了芝麻油和表面活性剂中普罗布考(作为替代活性成分)与二氧化硅的重量比为2:1、3:1和4:1的最大药物载量,同时保留了二氧化硅珠的自由流动能力。如表1所示,XDP 3150磁珠和LC150A磁珠的休止角在35-40°之间,表示可通过的流动性。而US2磁珠的休止角为30°,如表1所示。与XDP 3150磁珠和LC150A磁珠相比,它具有更好的流动性。在最大载药量下,当以在芝麻油,表面活性剂和形成凝胶的赋形剂中的普罗布考(作为替代活性成分)与二氧化硅2:1重量比装载时,XDP 3150磁珠和LC150A磁珠显示出其流动性下降。US2磁珠在芝麻油,表面活性剂和形成凝胶的赋形剂与二氧化硅的普罗布考(作为替代活性成分)的重量比为2:1和3:1的情况下仍保持其自由流动的特性。但是,在4:1的比例下,US2磁珠的流动性似乎降低了。因此,基于评估,US2珠被鉴定在芝麻油,表面活性剂和凝胶形成赋形剂中的普罗布考(作为替代活性成分)与二氧化硅的优化药物载量为2:1和3:1的重量比的载体底物。然而,XDP3150和LC150A载体基质仍然显示出有利于用作本发明组合物的核心的性能。
在本发明的实施方案中,在组合物中使用一种或多种表面活性剂。表面活性剂促进自我乳化。当形成乳液时,在两相之间产生表面积扩大。乳液被表面活性剂分子稳定,该表面活性剂分子在内相液滴周围形成薄膜。在乳液形成中,过量的表面自由能取决于液滴尺寸和界面张力。如果使用表面活性剂无法稳定乳液,则两相将分开,从而降低界面张力和自由能。包括自微乳化药物输送系统(“SMDDS”)的自乳化药物输送系统(“SEDDS”)是天然或合成油,固体或液体表面活性剂或一种或多种亲水性溶剂和助溶剂的混合物能够在温和搅拌下形成水包油乳液的表面活性剂,然后在水性介质(如胃肠液)中稀释。胃和肠的消化运动为自身乳化提供了必要的搅动。
在本发明中,可以包括表面活性剂以使一种或多种大麻素从核的孔的完全释放最大化。大麻素可以是疏水的,它们在胃肠道的水性介质中溶解后的释放取决于各种内在因素,例如流体体积,蠕动,浓度梯度,食物效应,胆盐和转运时间。由于一种或多种大麻素在多孔核上的装载是通过毛细作用实现的,并且考虑到疏水性大麻素对核的更大亲和力,因此一种或多种大麻素从孔中的释放保证了乳化作用。
在一些实施方案中,本发明的组合物中的一种或多种表面活性剂可包含例如脱水山梨糖醇酯,乙氧基化山梨糖醇酯(80;Sigma Aldrich,美国),乙氧基化线性醇,乙氧基化烷基酚,脂肪酸酯,胺和酰胺衍生物,烷基聚葡糖苷,环氧乙烷/环氧丙烷共聚物,多元醇和乙氧基化多元醇,硫醇(例如硫醇)和衍生物,泊洛沙姆,聚乙二醇脂肪酸酯,卵磷脂及其混合物。在某些实施方案中,表面活性剂可以选自聚山梨酯(80;SigmaAldrich,美国)和蓖麻油酸的聚乙二醇酯(RH40,EL;德国BASF)。
本发明的组合物可以进一步包含一种或多种稳定剂。稳定剂的实例包括但不限于生育酚,烷基没食子酸酯,丁基化羟基茴香醚,丁基化羟基甲苯,抗坏血酸,异抗坏血酸,亚硫酸的钾盐(例如,焦亚硫酸氢钾),亚硫酸的钠盐(例如,钠(亚硫酸氢盐),维生素E,卵磷脂,抗坏血酸棕榈酸酯,乙二胺四乙酸,乙二胺四乙酸盐(例如EDTA)或其组合。稳定剂可以按重量计约0.001%至约5%的量存在于组合物中,或适当地存在以达到稳定的组合物。
本发明的组合物可以呈各种剂型,例如在胶囊剂,片剂,小药囊,洒水剂或棒状包装中。为此,组合物可进一步包含常规的赋形剂,例如稀释剂,粘合剂,填充剂,润滑剂,崩解剂或湿润剂。
稀释剂的实例包括但不限于纤维素衍生物,例如乳糖,蔗糖,异麦芽酮糖,纤维素,淀粉,环糊精,甘露醇,微晶纤维素和山梨糖醇;碳酸钙;纯或无水磷酸钙;磷酸氢钙;脱水二碱或三碱磷酸钙;碳酸镁;氧化镁;淀粉;氯化钠;及其组合。
粘合剂包括但不限于糖,例如蔗糖,乳糖,和葡萄糖;玉米糖浆;大豆多糖;明胶;聚维酮(例如);支链淀粉;纤维素衍生物,例如微晶纤维素,羟丙基甲基纤维素(例如),羟丙基纤维素(例如),乙基纤维素,羟乙基纤维素,羧甲基纤维素钠和甲基纤维素;丙烯酸和甲基丙烯酸共聚物;卡波姆(例如);聚乙烯基聚吡咯烷,聚乙二醇药用釉;海藻酸盐,例如海藻酸和海藻酸钠;树胶,如合欢树(Acacia),瓜尔胶,和阿拉伯树胶;黄蓍胶;糊精和麦芽糊精;乳衍生物,如乳清;淀粉,如预糊化淀粉和淀粉糊;氢化植物油;硅酸铝镁;及其组合。
填充剂可以增加剂型的体积并且可以使剂型更易于处理。实施性填充剂包括但不限于,用于固体剂型例如片剂和胶囊剂的乳糖,右旋糖,甘露醇,纤维素,淀粉和磷酸钙;橄榄油和油酸乙酯用于软胶囊;用于液体剂型的水和植物油,例如混悬剂和乳剂。其他合适的填充剂,包括但不限于蔗糖,葡萄糖结合剂,糊精,麦芽糖糊精,微晶纤维素(例如PH102或PH200,),超细纤维素,粉状纤维素,预胶化淀粉(例如Starch),磷酸钙二水合物,大豆多糖(例如),明胶,二氧化硅,硫酸钙,碳酸钙,碳酸镁,氧化镁,山梨糖醇,高岭土,聚甲基丙烯酸酯(例如),氯化钾,氯化钠,滑石粉及其组合。剂型可以使用一种或多种填充剂。
崩解剂可包括但不限于交聚维酮,结晶纤维素,低取代度的羟丙基纤维素,交联羧甲基纤维素钠,羧甲基纤维素钙,羧淀粉钠,羧甲基淀粉钠,马铃薯淀粉,小麦淀粉,玉米淀粉中的一种或多种淀粉,大米淀粉,部分预糊化的淀粉,羟丙基淀粉,微晶纤维素,藻酸盐,碳酸盐及其组合。
润滑剂的实例可包括轻质无水硅酸,硬脂酸镁,硬脂酸,硬脂酸钙,硬脂酸铝,单硬脂酸铝,蔗糖脂肪酸酯,聚乙二醇,硬脂富马酸钠,硬脂醇,滑石粉,氧化钛,含水二氧化硅,硅酸镁,合成硅酸铝,磷酸氢钙,硬化蓖麻油,硬化菜籽油,巴西棕榈蜡,蜂蜡,微晶蜡和十二烷基硫酸钠。可以使用一种或两种或更多种润滑剂。
一种或多种亲水性聚合物可以以本发明的剂型使用。实例包括但不限于天然或部分或完全合成的亲水性树胶,例如阿拉伯胶,黄蓍胶,刺槐豆胶,瓜尔豆胶和卡拉胶;纤维素衍生物,例如甲基纤维素,羟甲基纤维素,羟丙基甲基纤维素,羟丙基纤维素,羟乙基纤维素和羧甲基纤维素;蛋白质物质,例如琼脂,果胶,角叉菜胶和藻酸盐;亲水性聚合物,例如羧基聚亚甲基;明胶;酪蛋白;玉米蛋白;膨润土;硅酸铝镁;多糖;改性淀粉衍生物;和本领域已知的其他亲水性聚合物。另外的例子是卡波姆,例如Carbopol 971P。
润湿剂可包括但不限于普鲁尼克尼克剂,聚乙二醇,脱水山梨糖醇酯,聚山梨酯,例如聚山梨酯20和聚山梨酯80,氚核,三羟甲基氨基甲烷,卵磷脂,胆固醇,替罗沙泊及其组合。
在一些实施方案中,组合物为包含包衣的片剂或胶囊剂形式。
另外,如本领域中已知的,所述组合物可以包含一种或多种天然和/或人造甜味剂和调味剂,或其组合。甜味剂/调味剂的实例可包括但不限于糖,右旋糖,果糖,阿斯巴甜,甘油,甘露醇,蔗糖,糖精钠,乙酰磺胺酸钾,右旋糖,液体葡萄糖,麦芽糖醇,糖精,糖精钙,糖精钠,甜蜜素,山梨糖醇,甜菊糖,糖浆,木糖醇及其组合。
在本发明的实施方案中,本发明的组合物可显示出具有缓释特征的溶出曲线。在一些实施方案中,当以水作为溶解介质时,本发明的组合物可显示一种或多种大麻素的在30分钟后释放重量百分比不大于约20%,或不大于约30%,或不大于40%,或不大于50%;60分钟后释放重量不大于约30%,或不大于约40%,或不大于约50%,或不大于约60%;120分钟后释放重量不大于约40%,或不大于约50%,或不大于约60%,或不大于约70%。
制备本发明组合物的方法
根据本发明的实施方案,可以通过将一种或多种大麻素在一种或多种增溶剂中与一种或多种凝胶形成剂(以及在一些实施方式中,一种或多种表面活性剂,以及任选地一种或多种稳定剂)混合来制备包含一种或多种本发明的大麻素的组合物。在一个实施方案中,一种或多种表面活性剂,和任选地一种或多种稳定剂,并将混合物加载到多孔核上。根据这些实施方式的组合物可以通过以下方式制备:将一种或多种大麻素和一种或多种凝胶形成剂(以及在一些实施方式中,一种或多种表面活性剂,以及任选地一种或多种稳定剂)在一种或多种增溶剂中混合,例如,超声仪和/或涡旋混合器。这些组分可以以任何顺序混合在一种或多种增溶剂中(例如,首先将一种或多种大麻素混合在一种或多种增溶剂中,然后添加一种或多种凝胶形成剂,并且在一些实施方案中,添加一种或多种表面活性剂,或先在一种或多种增溶剂中混合一种或多种表面活性剂,然后添加一种或多种大麻素和一种或多种凝胶形成剂,或同时添加和混合每种成分等)。在一些实施方案中,可将一种或多种大麻素和一种或多种增溶剂与超声仪混合直至均匀,然后将一种或多种表面活性剂(在一些实施方案中)和一种或多种凝胶形成剂(以及任选地一种或多种)混合。可以加入更多的稳定剂,并使用涡旋混合器混合。然后可以通过将混合物与核混合将混合物加载到多孔核上。在某些实施方案中,可使用高剪切制粒机将一种或多种大麻素/一种或多种凝胶形成剂/其他组分的混合物与多孔核混合。此后,形成根据本发明的组合物。
本发明的组合物可以使用常规方法制备为胶囊剂,片剂,小药囊,洒水剂或棒状包装。
本发明的组合物的应用
本发明的一方面涉及在有需要的受试者中治疗健康问题的方法,其中所述方法包括施用本发明的缓释组合物。
本发明还涉及本发明的缓释组合物在需要治疗的受试者中治疗健康问题的用途。所述用途可包括将所述组合物施用于受试者。
本发明涉及本发明的缓释组合物在制备用于治疗需要治疗的受试者健康问题的药物中的用途。
本发明还进一步涉及本发明的缓释组合物在需要治疗的受试者中治疗健康问题的用途。所述用途可包括将所述组合物施用于受试者。
健康问题可以选自疼痛,恶心,睡眠呼吸暂停,压力障碍,炎症,抑郁,焦虑,癫痫,精神分裂症,偏头痛,关节炎,体重减轻,食欲不振及其组合。
在一些实施方案中,可以口服施用组合物。
在一些实施方案中,在施用之前,可以将组合物撒在固体,半固体,或液体的食物或营养物上;水中;或放入其他类型的液体饮料中。
实施例
例子1
进行了研究以评估包含不同表面活性剂的速释组合物(参考组合物A-C)和缓释组合物(实施例组合物A-C)。这项研究检查了组合物的溶出曲线,以评估每种表面活性剂的乳化能力,并评估了缓释组合物中的药物释放剂。
速释组合物是包含多孔二氧化硅珠核的颗粒;替代活性成分,普罗布考;以及选自80(参考组合物A),RH40(参考组合物B)或EL(参考组合物C)的表面活性剂。表2总结了这些组成,包括每种成分的量。在每种速释组合物中,芝麻油与表面活性剂的重量比为1:5。为了制备组合物,将普罗布考加入到玻璃烧杯中的芝麻油中,并使用超声仪获得均匀的混合物。将表面活性剂加入到混合物中,并使用涡旋混合器形成均匀的混合物。然后使用高剪切制粒机将混合物加载到US2硅胶微珠的孔中,以获得均匀的药物加载微珠。
表2.组分汇总和参考组合物A-C的含量(%w/w)。
缓释组合物是的颗粒,其包含多孔二氧化硅珠核;替代活性成分,普罗布考;作为凝胶形成剂的甘油单油酸酯;以及表面活性剂。其中,表面活性剂选自与甘油单油酸酯(实施例组合物A)的重量比为1:1的80;与甘油单油酸酯(实施例组合物B)的重量比为11.5:1的RH40;和与甘油单油酸酯(实施例组合物C)的重量比为约5.25∶1的EL。表3汇总这些组成,包括每种成分的量。为了制备组合物,将普罗布考尔加入到玻璃烧杯中的芝麻油中,并使用超声仪获得均匀的混合物。将表面活性剂和甘油单油酸酯添加到混合物中,并使用涡旋混合器形成均匀的混合物。然后使用高剪切造粒机将混合物加载到US2硅微珠的孔中。
表3.组分汇总及实施例组合物A-C的组分其量(%w/w)。
使用纯净水USP作为溶出介质,以900ml的溶出体积对组合物进行溶出试验。使用USP II型桨叶设备以75rpm的桨叶速度混合溶解介质。浴温为37℃,并且使用10μm的多孔过滤器取样等分试样。
每种速释参考组合物A-C的溶出曲线在表4和图3A中提供。如表8所示,表面活性剂80能够在15分钟内促进在溶出介质中释放超过80%w/w的普罗布考,如表4所示。如表4所示,表面活性剂RH 40和EL都能够在5分钟内促进从溶解介质中的硅胶孔中释放80%w/w的芝麻油中的普罗布考。
表4.参考组合物A-C的溶出曲线。
图3A示出了所有评估的表面活性剂归因于在溶解介质中大于80%w/w的药物释放。EL表现出最高的乳化能力,可在24小时后从二氧化硅孔中释放出100%w/w的药物,而RH40为85%w/w,而80为88%w/w。
表5和图3B中提供了每种缓释的实施例组合物A-C的溶出曲线。使用80作为表面活性剂的实施组合物A的溶出曲线表明,药物释放在最初的6小时内被延长,以达到50%w/w的药物释放-从而零级释放-最多持续24小时(请参见表5和图3B)。
使用RH40作为表面活性剂的实施例组合物B的溶出度曲线显示,到5分钟时药物释放量超过80%w/w(参见表5和图3B)。类似地,使用EL作为表面活性剂的实施例组合物C的溶出曲线显示5分钟时药物释放量为79%w/w,15分钟时药物释放量超过80%w/w(参见表5和图3B)。
表5.实施例组合物A-C的溶出曲线。
这些结果证明甘油单油酸酯作为凝胶形成剂能够提供延长的释放特性。另外,假设甘油单油酸酯的亲水性可能增加了珠的乳化作用,从而导致药物在溶出介质中的释放更高。
例子2
进行了研究以评估颗粒的五种缓释组合物(实施例组合物D-H),其包含多孔二氧化硅珠核;替代活性成分普罗布考;作为凝胶形成剂的甘油单油酸酯;以及与甘油单油酸酯的比例不同的表面活性剂EL。表6汇总了这些成分,包括每种成分的数量。
为了制备组合物,将普罗布考尔加入到玻璃烧杯中的芝麻油中,并使用超声仪获得均匀的混合物。将EL和甘油单油酸酯添加到混合物中,并使用涡旋混合器形成均匀的混合物。然后使用高剪切造粒机将混合物加载到US2硅微珠的孔中。
在实施例组合物D-H上进行溶解试验,使用纯净水USP作为溶解介质,溶解体积为900ml。使用USP II型桨叶设备以75rpm的桨叶速度混合溶解介质。浴温为37℃,并且使用10μm的多孔过滤器取样等分试样。
表7和图4提供了每种组合物的溶出曲线。实施例组合物D-F的溶出曲线显示5分钟内90%w/w或更高的药物释放,这表明没有实现缓释。实施例组合物G的溶出曲线在5分钟内显示出70%w/w的药物释放,但是在24小时内释放保持低于80%w/w。实施例组合物H的溶出曲线在5分钟时显示出50%w/w的药物释放,到120分钟时上升到80%w/w。
表6.实施组合物D-H的成分及其数量(%w/w)的汇总。
表7.实施组合物D-H的溶出曲线。
这些结果表明,甘油单油酸酯作为凝胶形成剂能够提供延长的释放特性。
例子3
进行了研究以比较颗粒的速释组合物(参考组合物D)和缓释组合物(实施例组合物I),其中颗粒包括包含多孔二氧化硅珠核;大麻素THC;和表面活性剂80。所述延长释放体位的颗粒,还包括作为凝胶形成剂的单油酸甘油酯。表8汇结了这些组成,包括每种成分的量。
为了制备速释参考组合物D,将THC加入玻璃烧杯中的芝麻油中,并使用超声仪获得均匀的混合物。将表面活性剂80加入混合物中,并使用涡旋混合器形成均匀的混合物。然后使用高剪切造粒机将混合物加载到US2硅微珠的孔中。
为了制备缓释实施例组合物I,将THC加入到玻璃烧杯中的芝麻油中,并使用超声仪获得均匀的混合物。将表面活性剂80和甘油单油酸酯添加到混合物中,并使用涡旋混合器形成均匀的混合物。然后使用高剪切造粒机将混合物加载到US2硅微珠的孔中。
使用纯净水USP作为溶出介质,对速释参考组合物D和缓释实施组合物I进行溶出试验,溶出体积为900ml。使用USP II型桨叶设备以75rpm的桨叶速度混合溶解介质。浴温为37℃,并且使用10μm的多孔过滤器取样等分试样。
表9以及图5A和5B提供了每种组合物的溶出曲线。速释参考组合物D的溶出曲线显示5分钟后80%w/w THC释放,到12小时时约100%w/w THC释放(参见表9和图5A)。相反,缓释实施例组合物I的溶出曲线在5分钟后显示出小于20%w/w的THC释放,并且在12小时后显示小于60%w/w的药物释放(参见表9和图5B)。
表8.速释参考组合物D和缓释实施组合物I的成分及其含量(%w/w)的汇总。
表9.速释参考组合物D和缓释实施组合物I的溶出度曲线。
这些结果表明,甘油单油酸酯作为凝胶形成剂能够延长THC的释放。
例子4
进行研究以比较颗粒的速释组合物(参考组合物E)和缓释组合物(实施组合物J),其中颗粒包含多孔二氧化硅珠核;大麻素CBD;和表面活性剂80。缓释组合物的颗粒另外包含作为凝胶形成剂的单油酸甘油酯。表10总结了这些组成,包括每种成分的量。
为了制备速释参考组合物E,将CBD添加到玻璃烧杯中的芝麻油中,并使用超声仪获得均匀的混合物。将表面活性剂80加入混合物中,并使用涡旋混合器形成均匀的混合物。然后使用高剪切造粒机将混合物加载到US2硅微珠的孔中。
为了制备缓释实施组合物J,将CBD添加到玻璃烧杯中的芝麻油中,并使用超声仪获得均匀的混合物。将表面活性剂80和甘油单油酸酯添加到混合物中,并使用涡旋混合器形成均匀的混合物。然后使用高剪切造粒机将混合物加载到US2硅微珠的孔中。
使用纯水USP作为溶出介质,以900ml的溶出体积,对速释参考组合物E和缓释实施组合物J进行溶出试验。使用USP II型桨叶设备以75rpm的桨叶速度混合溶解介质。浴温为37℃,并且使用10μm的多孔过滤器取样等分试样。
表11以及图6A和6B提供了每种组合物的溶出曲线。速释参考组合物E的溶出曲线显示5分钟后释放出超过70%w/w的CBD,到15分钟时释放出超过90%w/w的CBD(请参阅表11和图6A)。相反,缓释实施例组合物J的溶出曲线显示5分钟后小于25%w/w的CBD释放,和12小时后小于70%w/w的CBD释放(参见表11和图6B)。
表10.速释参考组合物E和缓释实施组合物J的成分及其含量(%w/w)的汇总。
表11.速释参考组合物E和缓释实施组合物J的溶出度曲线。.
这些结果证明,甘油单油酸酯作为凝胶形成剂能够延长CBD的释放。
例子5
进行研究以比较颗粒的速释组合物(参考组合物F)和缓释组合物(实施例组合物K),其中颗粒包含多孔二氧化硅珠核;大麻素THC和CBD;胶囊的表面活性剂80。缓释组合物的颗粒另外包含作为凝胶形成剂的甘油单油酸酯。表12总结了这些组成,包括每种成分的量。
为了制备速释参考组合物F,将THC和CBD添加到玻璃烧杯中的芝麻油中,并使用超声仪获得均匀的混合物。将表面活性剂80加入混合物中,并使用涡旋混合器形成均匀的混合物。然后使用高剪切造粒机将混合物加载到US2二氧化硅珠粒的孔中,并将所得颗粒放入胶囊中。
为了制备缓释实施例组合物K,将THC和CBD添加到玻璃烧杯中的芝麻油中,并使用超声仪获得均匀的混合物。将表面活性剂80和甘油单油酸酯添加到混合物中,并使用涡旋混合器形成均匀的混合物。然后使用高剪切造粒机将混合物加载到US2二氧化硅珠粒的孔中,并将所得颗粒放入胶囊中。
使用纯净水USP作为溶出介质,以900ml的溶出体积,对速释参考组合物F和缓释实施组合物K进行溶出试验。使用USP II型桨叶设备以75rpm的桨叶速度混合溶解介质。浴温为37℃,并且使用10μm的多孔过滤器取样等分试样。
表13(用于两种组合物的THC的释放)和表14(用于两种组合物的CBD的释放)和图7A(速释参考组合物F中THC和CBD的释放)和图7B(缓释实施组合物K中THC和CBD的释放)提供了每种组合物的溶出曲线。对于THC和CBD而言,速释参考组合物F的溶出度曲线显示,在30分钟内释放超过60%w/w,到12小时释放超过90%w/w(参见表13和14,以及图7A)。相反,对于THC和CBD而言,缓释实施组合物K的溶出度曲线显示,30分钟后释放量小于5%w/w,12小时后释放量小于60%w/w(请参见表13和表14,和图7B)。
表12.速释参考组合物F和缓释实施组合物K的成分及其含量(%w/w)的摘要。
表13.速释参考组合物F和缓释实施组合物K的THC溶出曲线。
表14.速释参考组合物F和缓释实施组合物K的CBD的溶解曲线。
这些结果表明,甘油单油酸酯作为凝胶形成剂能够延长THC和CBD的释放。
还进行了分析以检查将THC和CBD装载到二氧化硅珠上对物理特性的影响。图8A-8C和图8D-8E分别比较了普通Neusilin US2二氧化硅珠和速释参考组合物F的颗粒的物理外观。与普通的Neusilin US2二氧化硅微珠相比,装载有THC和CBD的颗粒具有更粗糙的表面。
另外,在图9A和9B中示出了普通Neusilin US2二氧化硅珠和速释参考组合物F的颗粒的粒度分布的比较。与速释参考组合物F的颗粒相比,普通的Neusilin US2二氧化硅微珠表现出更宽的粒径分布和更少的直径约40mm或更大的颗粒(参见图9A和图9B)。
例子6
使用超声波发生器在玻璃烧杯中的芝麻油中加入THC,以获得均匀的混合物。将80和凝胶形成剂甘油单油酸酯添加到混合物中,并使用涡旋混合器均匀混合。使用高剪切造粒机将混合物加载到US2硅胶微珠的孔中,以获得均匀的药物加载微珠。80用作表面活性剂,甘油单油酸酯的比例为1:1。将所得的多颗粒装载到胶囊中。
例子7
使用超声波发生器在玻璃烧杯中的芝麻油中加入CBD,以获得均匀的混合物。将80和凝胶形成剂甘油单油酸酯添加到混合物中,并使用涡旋混合器均匀混合。使用高剪切造粒机将混合物加载到US2硅胶微珠的孔中,以获得均匀的药物加载微珠。80用作表面活性剂,甘油单油酸酯的比例为1:1。将所得的多颗粒组合物压制成片剂。
例子8
使用超声仪将THC和CBD组合加入玻璃烧杯中的芝麻油中以获得均匀的混合物。将80和凝胶形成剂甘油单油酸酯添加到混合物中,并使用涡旋混合器均匀混合。使用高剪切造粒机将混合物加载到US2硅胶微珠的孔中,以获得均匀的药物加载微珠。80用作表面活性剂,甘油单油酸酯的比例为1:1。将所得的含有CBD和THC的多颗粒填充到胶囊中。
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尽管这里已经公开了本发明的特定实施例,但是本领域普通技术人员将理解,可以在不脱离本发明的精神的情况下对特定实施例进行改变。因此,本发明的范围不限于特定实施例。此外,意图是所附权利要求覆盖本发明范围内的任何和所有这样的应用,修改和实施例。
Claims (14)
1.用于缓释一种或多种大麻素的组合物,所述组合物包含颗粒群,其中每个颗粒包含:
(a)1%至2%w/w的一种或多种大麻素;
(b)5%至15%w/w的一种或多种增溶剂;
(c)15%至35%w/w的一种或多种药物释放剂;
(d)20%至45%w/w的核;和
(e)15%至35%w/w的至少一种表面活性剂;
其中所述组合物在至少6小时的时间内释放一种或多种大麻素;
其中一种或多种药物释放剂包含一种或多种基于脂质的凝胶形成剂。
2.根据权利要求1所述的组合物,其中所述一种或多种大麻素包括Δ9-四氢大麻酚(THC),大麻二酚(CBD),或其组合物。
3.根据权利要求1所述的组合物,其中所述一种或多种凝胶形成剂包括甘油单油酸酯。
4.根据权利要求1所述的组合物,其中所述核包含二氧化硅珠或多孔的可生物降解的玻璃珠。
5.根据权利要求1所述的组合物,其中所述核包含从所述核的表面延伸的一个或多个孔。
6.根据权利要求5所述的组合物,其中所述一个或多个孔含有一种或多种大麻素、一种或多种增溶剂、一种或多种药物释放剂,以及一种或多种表面活性剂。
7.根据权利要求6所述的组合物,其中所述孔配置为使得所述一种或多种药物释放剂位于比所述一种或多种大麻素和所述一种或多种表面活性剂更靠近所述核的表面的孔中。
8.根据权利要求1-7中任一项所述的组合物,其中所述表面活性剂选自由脱水山梨糖醇酯,乙氧基化脱水山梨糖醇酯,脂肪酸酯,多元醇,乙氧基化多元醇,乙氧基化线性醇,乙氧基化烷基酚,胺衍生物,酰胺衍生物,烷基聚葡糖苷,环氧乙烷-环氧丙烷共聚物,硫醇或其衍生物,泊洛沙姆,聚乙二醇-脂肪酸酯,卵磷脂,及其混合物。
9.根据权利要求8所述的组合物,其中所述表面活性剂选自聚山梨酸酯和蓖麻油酸的聚乙二醇酯。
10.根据权利要求1所述的组合物,其中所述一种或多种增溶剂包括油,醇,水醇混合物,或其组合物。
11.根据权利要求10所述的组合物,其中所述一种或多种增溶剂包含油,所述油选自大麻油,琉璃苣油,椰子油,棉籽油,大豆油,红花油,向日葵油,蓖麻油,玉米油,橄榄油,棕榈油,花生油,杏仁油,芝麻油,菜籽油,薄荷油,罂粟籽油,低芥酸菜子油,棕榈仁油,氢化大豆油,氢化植物油,及其组合物。
12.根据权利要求10所述的组合物,其中所述一种或多种增溶剂包括一元醇或水醇混合物。
13.根据权利要求12所述的组合物,其中所述一元醇是乙醇,甲醇,或异丙醇。
14.根据权利要求1所述的组合物,其中所述颗粒以胶囊,片剂或小袋的形式提供。
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Families Citing this family (20)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2020016658A2 (en) * | 2018-07-18 | 2020-01-23 | Glatt Gmbh | Immediate release formulations of cannabinoids |
WO2020092352A1 (en) * | 2018-10-30 | 2020-05-07 | Kelsie Biotech, Llc | Tablets, formulations and methods for low melting point active ingredients |
US20220096398A1 (en) * | 2019-01-31 | 2022-03-31 | Macquarie University | Complexes and compositions comprising probucol and uses thereof |
CA3040547C (en) * | 2019-04-17 | 2021-12-07 | Medcan Pharma A/S | Cannabinoid lozenge formulation |
US20210290564A1 (en) * | 2020-03-17 | 2021-09-23 | Tauriga Sciences Inc. | Medicated cannabinoid compositions, methods of manufacturing, and methods of treatment |
WO2021228366A1 (en) * | 2020-05-11 | 2021-11-18 | Add Advanced Drug Delivery Technologies Ltd. | Uses and formulations of cannabinoids |
AU2021270970A1 (en) * | 2020-05-11 | 2022-12-15 | Add Advanced Drug Delivery Technologies Ltd. | Uses and formulations of cannabinoids |
US11752185B2 (en) | 2020-05-29 | 2023-09-12 | Hemp Corporation | Powderized cannabis oil |
EP4164613A1 (en) * | 2020-06-20 | 2023-04-19 | Chavan, Neha | Compositions for solubilizing water-insoluble active ingredients |
WO2021263132A1 (en) | 2020-06-26 | 2021-12-30 | Aprecia Pharmaceuticals LLC | Rapidly-orodispersible tablets having an interior cavity |
CN111804166B (zh) * | 2020-08-19 | 2021-05-04 | 浙江新维士生物科技有限公司 | 一种混悬软胶囊防渗漏低温配料生产工艺 |
IT202000027408A1 (it) * | 2020-11-16 | 2022-05-16 | Indena Spa | Dispersioni solide di cannabidiolo |
WO2022148672A1 (en) * | 2021-01-08 | 2022-07-14 | Société des Produits Nestlé S.A. | Oral solid cannabinoid oil composition for treating central nervous system disorders |
WO2023002200A1 (en) * | 2021-07-22 | 2023-01-26 | Nicoventures Trading Limited | Constituent, derivative or extract of cannabis in amorphous form |
CA3224624A1 (en) * | 2021-07-22 | 2023-01-26 | Steven Alderman | Composition comprising a constituent, derivative or extract of cannabis |
WO2023002195A1 (en) * | 2021-07-22 | 2023-01-26 | Nicoventures Trading Limited | Methods of preparing compositions comprising a constituent, derivative or extract of cannabis |
EP4373302A1 (en) * | 2021-07-22 | 2024-05-29 | Nicoventures Trading Limited | Constituent, derivative or extract of cannabis in a water soluble matrix |
WO2023166409A1 (en) * | 2022-03-04 | 2023-09-07 | Buzzelet Development And Technologies Ltd. | Compositions comprising at least one of a terpene and a cannabinoid and uses thereof |
GB2618322A (en) * | 2022-04-29 | 2023-11-08 | 113 Botanicals Ltd | Compositions and methods |
WO2024033521A1 (en) * | 2022-08-12 | 2024-02-15 | GW Research Limited | Oral solid dosage forms comprising cannabinoids |
Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2017072762A1 (en) * | 2015-10-26 | 2017-05-04 | Yissum Research Development Company Of The Hebrew University Of Jerusalem Ltd | Novel cannabinoid formulations |
WO2018035030A1 (en) * | 2016-08-15 | 2018-02-22 | Corr-Jensen Inc. | Time release fat-soluble actives |
Family Cites Families (40)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5576016A (en) | 1993-05-18 | 1996-11-19 | Pharmos Corporation | Solid fat nanoemulsions as drug delivery vehicles |
WO2000018500A1 (de) | 1998-09-24 | 2000-04-06 | Glatt Systemtechnik Dresden Gmbh | Einrichtung zur herstellung eines schüttfähigen produktes und verfahren zur anwendung der einrichtung |
US6328992B1 (en) | 1997-03-03 | 2001-12-11 | Lawrence L. Brooke | Cannabinoid patch and method for cannabis transdermal delivery |
US5891496A (en) | 1997-08-06 | 1999-04-06 | Hannah; Scott C. | Fat-free chopped and formed potato products and process |
GB9726916D0 (en) | 1997-12-19 | 1998-02-18 | Danbiosyst Uk | Nasal formulation |
US6509005B1 (en) | 1998-10-27 | 2003-01-21 | Virginia Commonwealth University | Δ9 Tetrahydrocannabinol (Δ9 THC) solution metered dose inhaler |
AU3697200A (en) | 1999-02-04 | 2000-08-25 | New Millennium Pharmaceutical Research, Inc. | Method for enhancement of delivery of thc by the administration of its prodrugs via the nasal route |
DE10004939C1 (de) | 2000-02-05 | 2001-08-23 | Lothar Moerl | Steuerbare Gasanströmeinrichtung für Strahlschichtapparate |
NZ527289A (en) | 2001-02-14 | 2005-05-27 | Gw Pharma Ltd | Lipophilic medicaments and their administration via mucosal surfaces |
GB0103638D0 (en) * | 2001-02-14 | 2001-03-28 | Gw Pharmaceuticals Ltd | Pharmaceutical formulations |
DE10162781A1 (de) | 2001-12-20 | 2003-07-03 | Glatt Ingtech Gmbh | Strahlschichtapparat zur chargenweisen oder kontinuierlichen Prozessführung und Verfahren zum Betreiben eines Strahlschichtapparates |
US6946150B2 (en) | 2002-08-14 | 2005-09-20 | Gw Pharma Limited | Pharmaceutical formulation |
CN1747822A (zh) | 2002-12-10 | 2006-03-15 | Cps奥罗瑟尔有限责任公司 | 制备生物活性制剂的方法 |
DE10322062A1 (de) | 2003-05-15 | 2004-12-02 | Glatt Ingenieurtechnik Gmbh | Verfahren und Vorrichtung zum Aufbringen von Flüssigkeiten in eine Feststoffströmung eines Strahlschichtapparates |
TWI366460B (en) * | 2005-06-16 | 2012-06-21 | Euro Celtique Sa | Cannabinoid active pharmaceutical ingredient for improved dosage forms |
DE102005037630A1 (de) | 2005-08-09 | 2007-02-15 | Glatt Gmbh | Verfahren zur Herstellung von Teilchen aus pharmazeutischen Substanzen, Teilchen aus pharmazeutischen Substanzen sowie deren Verwendung |
WO2008021394A2 (en) * | 2006-08-15 | 2008-02-21 | Theraquest Biosciences, Llc | Pharmaceutical formulations of cannabinoids and method of use |
WO2008027442A2 (en) * | 2006-08-30 | 2008-03-06 | Theraquest Biosciences, Llc | Abuse deterrent oral pharmaceutical formulations of opioid agonists and method of use |
WO2009007768A1 (en) * | 2007-07-06 | 2009-01-15 | Gumlink A/S | Compressed tablet comprising polyol |
EP2135601A1 (en) * | 2008-06-20 | 2009-12-23 | Capsulution Nanoscience AG | Stabilization of amorphous drugs using sponge-like carrier matrices |
WO2011063164A2 (en) * | 2009-11-18 | 2011-05-26 | Steady Sleep Rx Co., Inc. | Sustained release cannabinoid medicaments |
US20180264013A1 (en) * | 2010-07-08 | 2018-09-20 | Wellesley Pharmaceuticals, Llc | Composition and methods for treating sleep disorders |
WO2012048045A1 (en) * | 2010-10-05 | 2012-04-12 | Jb Therapeutics, Inc. | Compositions, dosages, and methods of using tetrahydrocannabinol derivatives |
US20120231083A1 (en) * | 2010-11-18 | 2012-09-13 | The Board Of Trustees Of The University Of Illinois | Sustained release cannabinoid medicaments |
US20140186491A1 (en) * | 2011-07-05 | 2014-07-03 | Kraft Foods R & D, Inc. | Bitterness masking |
CN104363890B (zh) * | 2012-05-07 | 2018-01-26 | 回音制药公司 | 含有大麻素的颗粒物及其制备方法和含有该颗粒物的口服给药单元 |
GB201304662D0 (en) * | 2013-03-14 | 2013-05-01 | Sigmoid Pharma Ltd | Compositions |
WO2015040212A1 (en) * | 2013-09-20 | 2015-03-26 | Tillotts Pharma Ag | Delayed release pharmaceutical formulation |
US20160022627A2 (en) | 2014-04-18 | 2016-01-28 | Mary's Medicinals LLC | Transdermal cannabinoid patch |
US20160030345A1 (en) * | 2014-08-01 | 2016-02-04 | Johnson & Johnson Consumer Inc. | Core Compositions |
MX2017003561A (es) | 2014-08-22 | 2017-08-28 | Medipath Inc | Composiciones y metodos para revestimientos cannabinoides para su uso en la administracion de farmacos. |
CA3089686A1 (en) * | 2015-03-10 | 2016-09-15 | Nanosphere Health Sciences, Llc | A nanoparticle drug delivery comprising liquid lipids and cannabinoids encapsulated in a single layer of essential phospholipids |
WO2016205923A1 (en) | 2015-06-25 | 2016-12-29 | Compressed Perforated Puck Technologies Inc. | Ingestible plant source pill and method |
US10179109B2 (en) | 2016-03-04 | 2019-01-15 | Charleston Laboratories, Inc. | Pharmaceutical compositions comprising 5HT receptor agonist and antiemetic particulates |
EP3463287A1 (en) * | 2016-05-27 | 2019-04-10 | MedCan Pharma A/S | Powdered composition comprising a complex between a cannabinoid and a basic ion exchange resin |
CA3036585A1 (en) | 2016-09-27 | 2018-04-05 | CannTab Therapeutics Limited | Sustained release cannabinoid formulations |
JP2019530717A (ja) | 2016-10-12 | 2019-10-24 | コロンビア ケア エルエルシー | 抽出されたカンナビノイドの経口組成物およびその使用の方法 |
WO2018132893A1 (en) * | 2017-01-23 | 2018-07-26 | CannTab Therapeutics Limited | Immediate release cannabidiol formulations |
WO2019159174A1 (en) * | 2018-02-16 | 2019-08-22 | Icdpharma Ltd. | Colonic delivery of cannabinoids in solid solution compositions |
WO2020016658A2 (en) * | 2018-07-18 | 2020-01-23 | Glatt Gmbh | Immediate release formulations of cannabinoids |
-
2019
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-
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Patent Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2017072762A1 (en) * | 2015-10-26 | 2017-05-04 | Yissum Research Development Company Of The Hebrew University Of Jerusalem Ltd | Novel cannabinoid formulations |
WO2018035030A1 (en) * | 2016-08-15 | 2018-02-22 | Corr-Jensen Inc. | Time release fat-soluble actives |
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