Patent GB-740893-A (GB)
Title: Manufacture of preparations suitable for therapeutic application
IPC: A61K31/215
Filed: 1952-06-12
Abstract: As spasmolytic agents (see Group VI) are employed the esters of benzilic acid forming the subject of Specification 740,959, and also the methanol, ethanol, propanol-1 and -2, butanol-1, pentanol-1, 2-methylbutanol-4 and benzyl alcohol esters, the properties of which are given in a table.ALSO:Therapeutic preparations for internal application (as spasmolytics) comprise an ester, free from basic nitrogen, of benzilic acid with thymol or an alcohol containing not more than 12 carbon atoms in the molecule, together with a carrier suitable for therapeutic use for internal application.  For oral administration, the esters, as such or adsorbed or a solid adsorbent, may be worked up into wafer-seals, or, with fillers if necessary, into tablets, which may be sugar coated, or capsules may be filled with a solution, emulsion or suspension of the ester, e.g. in a fatty oil, or a suspension or emulsion of the ester in water may be taken as a draught.  For injection the esters may be dissolved in organic solvents (including fatty oils to which a wax may be added for forming a depot therapeutic material), or in water with the aid of solubilizing agents, or may be dispersed in water with the aid of a surface-active agent. They may also be formed into suppositories with a fatty basis.  In examples: (1) the 2-methylbutanol-1 ester is adsorbed on a mixture of lactose and oxidized starch, and the product, with the addition of talcum and magnesium stearate, is pressed into tablets, which in (2) are coated with a mixture of sugar, talcum venetum and gelatin; (3) gelatin capsules are filled with a solution of the heptanol-1 ester in arachis oil; (4) a wafer-seal is filled with a mixture of lactose and oxidized starch on which the benzyl ester is adsorbed; (5) a draught is prepared by dispersing the 2-ethyl-hexanol ester in an aqueous solution of sugar and a vegetable gum or carboxymethylcellulose; (6) ampoules are filled with a solution of the 2-methylpropanol-1 ester in 1 : 2-propylene glycol or a mixture thereof with benzyl alcohol and water, and then sterilized with steam; (7) suppositories are cast from a mixture prepared by stirring the 2-methylbutanol-1 ester into a melt of polyethylene sorbitan monostearate and glyceryl laurate. The spasmolytic properties of the esters with methanol, ethanol, propanol-1 and -2, butanol-1, pentanol-1, -2 and -3, 2-methylbutanol-4, fermentation amyl alcohol, heptanol-3, 2-methylhexanol-1, 2 : 6-dimethylheptanol-4, 3 : 5 : 5-trimethylhexanol-1, 5-ethylnonanol-2, dodecanol-1, 2 : 6 : 8-trimethylnonanol-4, 3 : 3 : 5-trimethylcyclohexanol, l-menthol, borneol and tetrahydrofurfuryl alcohol are also given, and still further alcohols are listed.  Additional carrier materials specified are: adsorbents: bolus alba and colloidal silicic acid; filler for tablets; saccharose; solvents: glycerol, glyceryl diethyl ether, and a mixture of alcohol, glycerol and water; substances increasing the solubility of the esters in water: methane, substituted amides, methylglucamine and polyvinylpyrrolidone; suppository base: cacao butter. Specification 740,959, [Group IV(b)], and U.S.A. Specification 2,399,736 are referred to.