An intravenous formulation of Δ9‐tetrahydrocannabinol using a non‐ionic surfactant
An intravenous formulation of Δ9‐tetrahydrocannabinol using a non‐ionic surfactant
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使用非离子表面活性剂的 Δ9-四氢大麻酚静脉注射制剂
DOI：
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发表时间：
1973
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影响因子：
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通讯作者：
A. Guarino
中科院分区：
文献类型：
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作者：
J. Cradock;J. Davignon;C. Litterst;A. Guarino
已经评价了先前用于增溶两种亚硝酸源（Davignon，Wood和克拉多克，1972）的乙醇-聚乙氧基化植物油（PEVO）* 和生理盐水（5：5：90）的混合溶剂系统对于A$-四氢大麻酚（As-THC）的增溶的适用性。将适量的Ag-THC（10 mg ml-1乙醇溶液，储存在4”下）在氮气下避光蒸发至干。依次或作为混合溶剂加入等体积的乙醇和PEVO，然后搅拌，并用9体积的生理盐水进一步稀释溶液。得到的溶液是澄清的，棕褐色的，并且含有0.5-10 mg Ag-THC ml-1。该制剂的效用在很大程度上取决于PEVO和乙醇的药理作用。溶血和低血压与吐温型表面活性剂有关（Krantz，卡尔等人，1948）。吐温引起的低血压是犬的一个严重问题，似乎与组胺释放有关。在其他动物和人类中，这种影响很轻微或不存在（Krantz等人，1948年）。尽管PEVO基本上不具有溶血性（Macek，1963），但已观察到对低血压易感性的相似种属差异（Schaeppi & Schaepan，1972）。我们对新西兰兔（1.3-1-6 kg）静脉内单独施用载体和A$-THC。三只兔子中有两只在注射A$-THC 100 mg kg-1作为14 mg ml-1制剂期间死亡。家兔出现惊厥、抽搐和显著的血管舒张，并在死亡前经历一段快速深呼吸，随后是浅间歇呼吸。在40 mg kg-1 Ag-THC（以7 mg ml-1溶液计）下，所有（4）只动物都表现出过度活跃，后肢表现出轻度强直性伸展，并在24小时观察期内存活。所有A$-THC处理的兔子在两个剂量水平下都表现出明显的瞳孔缩小。这些影响至少部分归因于As-THC，因为单独等量的载体不产生这些影响。对照组动物中仅出现轻微共济失调和抑郁。
The suitability of a mixed solvent system of ethanol-polyethoxylated vegetable oil (PEVO)* and physiological saline (5 :5 :90) previously used for the solubilization of two antineoplastic nitrosources (Davignon, Wood & Cradock, 1972), has been evaluated for solubilization of A$-tetrahydrocannabinol (As-THC). Appropriate amounts of Ag-THC (as a 10 mg ml-I solution in ethanol, stored at 4") were evaporated to dryness under nitrogen in the dark. Equal volumes of ethanol and PEVO were added either sequentially or as a mixed solvent and then agitated and the solution further diluted with 9 volumes of physiological saline. The resulting solutions were clear, tan coloured and contained 0.5-10 mg of Ag-THC ml-l. The utility of this formulation depends to a large extent on the pharmacological effects of PEVO and ethanol. Haemolysis and hypotension have been associated with Tween-type surfactants (Krantz, Carr & others, 1948). Tween-induced hypotension is a serious problem in canines and appears related to histamine release. In other animals and man this effect is slight or absent (Krantz & others, 1948). Although PEVO is essentially not haemolytic (Macek, 1963), similar species differences in susceptibility to hypotension have been observed (Schaeppi & Phelan, 1972). We administered the vehicle alone and with A$-THC intravenously to New Zealand rabbits (1.3-1-6 kg). Two of three rabbits died during injection of A$-THC 100 mg kg-l as a 14 mg ml-l formulation. The rabbits exhibited convulsions, twitches, and striking vasodilation and went through a period of rapid deep breathing followed by shallow intermittent breathing before death. At 40 mg kg-l Ag-THC (as 7 mg ml-l solution) all (4) animals were hyperactive, exhibited mild tonic extensions of hind limbs and survived a 24 h observation period. All A$-THC-treated rabbits at both dose levels exhibited marked miosis. These effects are attributed at least in part to As-THC since equal volumes of vehicle alone produced none of these effects. Only slight ataxia and depression were evident in control animals.