Claims for Patent: 5,488,150

Summary for Patent: 5,488,150

Title:	Crystals of N-(trans-4-isopropylcyclohexycarbonyl)-D-phenylalanine and methods for preparing them
Abstract:	Stable crystals of N-(trans-4-isopropylcyclohexylcarbonyl)-D-phenylalanine may be produced by treating this compound with a solvent at a temperature of at least 10.degree. C. and forming crystals in the solvent at a temperature of at least 10.degree. C. For example, crystals may be formed by crystallization out of solution, or may be formed from solid particles of the compound suspended in a solvent. Crystals formed in this way have different melting point, infra red spectrum and X-ray diffraction patterns from previously known forms of the compound and have enhanced processability, eg. stability to grinding.
Inventor(s):	Sumikawa; Michito (Kawasaki, JP), Koguchi; Yoshihito (Kawasaki, JP), Ohgane; Takao (Kawasaki, JP), Irie; Yasuo (Kawasaki, JP), Takahashi; Satoji (Yottukaichi, JP)
Assignee:	Ajinomoto Co., Inc. (Tokyo, JP)
Application Number:	08/166,144
Patent Claims:	1. A method for the production of crystals of N-(trans-4-isopropylcyclohexylcarbonyl)-D-phenylalanine having at least one of the following properties: (a) a melting point in the range of 136.degree.-142.degree. C.; (b) a powder X-ray diffraction pattern with reflection maxima at 2.theta. of about 8.1.degree., 13.1.degree., 19.6.degree. and 19.9.degree.; comprising dissolving or suspending N-(trans-4-isopropylcyclohexylcarbonyl)-D-phenylalanine in a solvent in which it is completely or incompletely soluble at a temperature of at least 10.degree. C. and up to the boiling point of the solvent and permitting said crystals to crystallize from or form in said solvent at a temperature of 10.degree. C. or in excess thereof. 2. A method according to claim 1 wherein N-(trans-4-isopropylcyclohexylcarbonyl)-D-phenylalanine is dissolved in a solvent in which it is soluble at a temperature of at least 10.degree. C. to form a solution and crystals are then crystallised from the solution at a temperature of 10.degree. C. or in excess thereof by addition of a poorer solvent or by lowering the temperature of the solution. 3. A method according to claim 2 wherein crystallisation from solution is effected by reducing the temperature of the solution to a temperature of 10.degree. C. or in excess thereof. 4. A method according to claim 2 wherein the crystallisation from solution is effected at a temperature of 10.degree. C. or in excess thereof by adding to the solution a further solvent selected such that the solubility of said N-(trans-4-isopropylcyclohexylcarbonyl)-C-phenylalanine in the mixture of the solvent and further solvent in less than in the solvent, the solubility being reduced to an extent such that crystals crystallize from the solvent mixture at a temperature in excess of 10.degree. C. 5. A method according to claim 1 wherein N-(trans-4-isopropylcyclohexylcarbonyl)-D-phenylalanine is combined at a temperature of at least 10.degree. C. with a solvent in which it is incompletely soluble at that temperature to form a suspension of solid N-(trans-4-isopropylcyclohexylcarbonyl)-D-phenylalanine, and said suspension is maintained at a temperature of at least 10.degree. C., thereby to form said crystals from said solids. 6. A method according to claim 1 further comprising separating said crystals from the solvent at a temperature in excess of 10.degree. C. 7. Crystals of N-(trans-4-isopropylcyclohexylcarbonyl)-D-Phenylalanine obtained by the method of claim 1. 8. Crystals of N-(trans-4-isopropylcyclohexylcarbonyl)-D-phenylalanine having at least one of the following properties: (a) a melting point in the range of 136.degree.-142.degree. C.; and (b) a powder X-ray diffraction pattern with reflection maxima at 2.theta. of about 8.1.degree., 13.1.degree., 19.6.degree. and 19.9.degree.. 9. Crystals of N-(trans-4-isopropylcyclohexylcarbonyl)-D-phenylalanine according to claim 8 having both of the properties (a) and (b). 10. Crystals of N-(trans-4-isopropylcyclohexylcarbonyl)-D-phenylalanine having an X-ray powder diffraction pattern as shown in FIG. 3. 11. A method according to claim 1 wherein the crystals formed contain a greater percentage content of crystals having at least one of the specified properties relative to the starting N-(trans-4-isopropylcyclohexylcarbonyl)-D-phenylalanine. 12. A pharmaceutical composition comprising an effective amount of crystals according to claim 8 and a pharmaceutically acceptable excipient, diluent or carrier. 13. A pharmaceutical composition comprising an effective amount of crystals according to claim 10 and a pharmaceutically acceptable excipient, diluent or carrier.