Amorphous substances, crystals, pharmaceutical compositions, preparation methods and uses of thiohydantoin compound or pharmaceutically acceptable salt thereof

A pharmaceutical preparation, characterized in that the pharmaceutical preparation comprises the amorphous substance according to claim 1, and at least one of a solvent, solubilizer or surfactant, gel matrix material and pH regulator;

• wherein the pharmaceutical preparation is a topical pharmaceutical preparation;
• and, the pharmaceutical preparation is a semi-solid preparation;
• wherein, the semi-solid preparation is a gel;
• wherein, the weight percentage of the amorphous substance in the gel is 0.1%-10.0%;
• and, the solvent is a combination of any one or more of alcohol solvents with water;
• wherein, the alcohol solvent includes any one of ethanol, propylene glycol, polyethylene glycol, diethylene glycol monoethyl ether, glycerin, isopropyl alcohol, benzyl alcohol, lanolin alcohols, butanediol, dipropylene glycol and butanol, or a combination thereof;
• and, the solubilizer or surfactant is any one or more of poloxamer 188, polyoxyethylene 40 hydrogenated castor oil, polyoxyethylene 35 castor oil, span 40, glyceryl mono-and distearate, polyethylene glycol (35) stearate, polyglyceryl-3 distearate and Tween 80;
• wherein the weight percentage of the solubilizer or surfactant in the gel is 1%-15%;
• and, the gel matrix material is any one or more of sodium carboxymethyl cellulose, methyl cellulose, hydroxypropyl methyl cellulose, hydroxypropyl cellulose, poloxamer 407 and carbomer;
• wherein, the amount of the gel matrix material in the gel is 0.01%-5.0%;
• and, the pH regulator is any one or more of tromethamine, sodium hydroxide, sodium bicarbonate, ethylenediamine, ethanolamine, ammonia water and triethanolamine;
• or, wherein the gel comprises, in percentage by weight, 0.5%-5% of an amorphous substance of the compound of formula I according to claim 1 and 1%-10% of tween 80;
• or, wherein the gel comprises, in percentage by weight, 0.5% of an amorphous substance of the compound of formula I according to claim 1, 29%-31% of dehydrated alcohol, 42%-44% of propylene glycol, 0.5%-0.7% of carbomer 971P, 0.2%-0.4% of triethanolamine, 3.0%-3.7% of Tween 80 and 20%-24% of water;
• or, wherein the gel comprises, in percentage by weight, 1.0% of an amorphous substance of the compound of formula I according to claim 1, 29%-31% of dehydrated alcohol, 40%-44% of propylene glycol, 0.5%-0.7% of carbomer 971P, 0.2%-0.4% of triethanolamine, 3.0%-5.0% of Tween 80 and 20%-24% of water;
• or, wherein the gel comprises, in percentage by weight, 2.0% of an amorphous substance of the compound of formula I, 29%-31% of dehydrated alcohol, 36%-39% of propylene glycol, 0.5%-0.7% of carbomer 971P, 0.2%-0.4% of triethanolamine, 5.5%-8.5% of Tween 80 and 20%-24% of water;
• or, the gel comprises, in percentage by weight, 1.0% of an amorphous substance of the compound of formula I according to claim 1, 30.0% of dehydrated alcohol, 42.6% of propylene glycol, 0.6% of carbomer 971P, 0.3% of triethanolamine, 3.5% of Tween 80 and 22.0% of water.

A pharmaceutical preparation, characterized in that the pharmaceutical preparation comprises the amorphous substance according to claim 1, and at least one of a solvent, solubilizer or surfactant, gel matrix material and pH regulator;

• wherein, the pharmaceutical preparation is a liquid preparation;
• and, the liquid preparation is a topical solution;
• wherein, the weight percentage of the amorphous substance according to claim 1 in the topical solution is 0.1%-10.0%;
• and, the solvent is a combination of any one or more of alcohol solvents with water;
• wherein, the alcohol solvent is any one of ethanol, propylene glycol, polyethylene glycol, diethylene glycol monoethyl ether, glycerin, isopropyl alcohol, benzyl alcohol, lanolin alcohols and butanediol, or a combination thereof;
• and, the solubilizer or surfactant is any one or more of poloxamer 188, polyoxyethylene 40 hydrogenated castor oil, polyoxyethylene 35 castor oil, span 40, glyceryl mono-and distearate, polyethylene glycol (35) stearate, polyglyceryl-3 distearate and Tween 80;
• wherein the weight percentage of the solubilizer or surfactant in the topical solution is 1%-15%;
• or, the topical solution comprises, in percentage by weight, 0.5%-5% of an amorphous substance of the compound of formula I according to claim 1 and 1%-10% of tween 80;
• or, the topical solution comprises, in percentage by weight, 0.45%-0.60% of an amorphous substance of the compound of formula I according to claim 1, 34%-38% of dehydrated alcohol, 44%-49% of propylene glycol, 2.5%-3.5% of Tween 80 and 9.0%-18.0% of water;
• or, the topical solution comprises, in percentage by weight, 1.9%-1.1% of an amorphous substance of the compound of formula I according to claim 1, 34%-38% of dehydrated alcohol, 44%-49% of propylene glycol, 2.5%-3.5% of Tween 80 and 9.0%-18.0% of water;
• or, the topical solution comprises, in percentage by weight, 1.9%-2.2% of an amorphous substance of the compound of formula I according to claim 1, 30%-40% of dehydrated alcohol, 46%-50% of propylene glycol, 6.0%-9.0% of Tween 80 and 4.0%-12.0% of water;
• or, the topical solution comprises, in percentage by weight, 1.06% of an amorphous substance of the compound of formula I according to claim 1, 37.23% of dehydrated alcohol, 47.88% of propylene glycol, 3.19% of Tween 80 and 10.64% of water.