Compositions controlling pH range of release and/or release rate
The present invention provides a composition controlling a pH range of release and/or a release rate, which contains (i) a thienotriazolodiazepine compound of the formula (I) and (ii) at least one kind of ingredient selected from the group consisting of a water-soluble polymer, an enteric polymer, a water-insoluble polymer and a porous polymer and/or a surfactant, as well as a production method thereof.
1. A composition controlling a pH range of release and/or a release rate, which comprises
(i) a thienotriazolodiazepine compound of the formula (I)
wherein X is a halogen, R 1 is C1-C4 alkyl, R 2 is C1-C4 alkyl, a is an integer of 1-4, R 3 is C1-C4 alkyl, C1-C4 hydroxyalkyl, C1-C4 alkoxy, phenyl optionally having substituent(s), or heteroaryl optionally having substituent(s), a pharmaceutically acceptable salt thereof or a hydrate thereof; and
(ii) at least one polymer selected from the group consisting of hydroxypropylmethylcellulose phthalate, methacrylic acid-methyl methacrylate copolymer and hydroxypropylmethylcellulose acetate succinate, which is a solid dispersion, and wherein the compound of the formula (I), a pharmaceutically acceptable salt thereof or a hydrate thereof is dispersed in the polymer.
2. The composition of claim 1 , which further comprises a surfactant.
3. The composition of claim 1 , wherein the compound of the formula (I) is (S)-2-[4-(4-chlorophenyl)-2,3,9-trimethyl-6H-thieno[3,2-f][1,2,4]triazolo[4,3-a][1,4]diazepin-6-yl]-N-(4-hydroxyphenyl)acetamide.
4. The composition of claim 3 , which is a therapeutic agent for an inflammatory disease in a neutral area in a gastrointestinal tract lumen.
5. The composition of claim 4 , wherein the inflammatory disease is ulcerative colitis or Crohn's disease.
6. A production method of the composition of claim 1 , which comprises dissolving or dispersing the compound of the formula (I), a pharmaceutically acceptable salt thereof or a hydrate thereof, and the polymer in a solvent, and evaporating the solvent.
7. The method of claim 6 , further comprising dissolving or dispersing a surfactant in the solvent.
8. A production method of the composition of claim 1 , which comprises melting the compound of the formula (I), a pharmaceutically acceptable salt thereof or a hydrate thereof to give a melt product, dissolving or dispersing the polymer in the melt product, and cooling for solidification.
9. The method of claim 8 , further comprising dissolving or dispersing a surfactant in the melt product.
10. A composition controlling a pH range of release and/or a release rate which is obtainable by the method of claim 6 .
11. A composition controlling a pH range of release and/or a release rate which is obtainable by the method of claim 8 .
12. A method for controlling a pH range of release and/or a release rate of a thienotriazolodiazepine compound of the formula (I)
wherein X is a halogen, R 1 is C1-C4 alkyl, R 2 is C1-C4 alkyl, a is an integer of 1-4, R 3 is C1-C4 alkyl, C1-C4 hydroxyalkyl, C1-C4 alkoxy, phenyl optionally having substituent(s), or heteroaryl optionally having substituent(s), a pharmaceutically acceptable salt thereof or a hydrate thereof,
which method comprises administering a composition to a patient,
wherein the composition comprises
(i) the compound of the formula (I), a pharmaceutically acceptable salt thereof or a hydrate thereof; and
(ii) at least one polymer selected from the group consisting of hydroxypropylmethylcellulose phthalate, methacrylic acid-methyl methacrylate copolymer and hydroxypropylmethylcellulose acetate succinate, and is a solid dispersion, and wherein the compound of the formula (I), a pharmaceutically acceptable salt thereof or a hydrate thereof is dispersed in the polymer.
13. The method of claim 12 , wherein the compound of the formula (I) is (S)-2-[4-(4-chlorophenyl)-2,3,9-trimethyl-6H-thieno[3,2-f][1,2,4]triazolo[4,3-a][1,4]diazepin-6-yl]-N -(4-hydroxyphenyl)acetamide.