Preparation for treatment of spinal cord injury
View Patent ↗The present invention is a solid sustained-release formulation comprising an agent for inhibiting semaphorin 3A as an active ingredient, which comprises an agent for inhibiting semaphorin 3A and pharmaceutically acceptable hardly water-soluble solid substance, in which the carrier is silicone.
1. A sustained-release formulation having a solid sheet or rod shape comprising:
a compound of Formula (1):
wherein R 1 is a hydrogen atom or a carboxyl group, R 2 is a hydrogen atom or a hydroxyl group, R 3 is a hydrogen atom or a carboxyl group, and R 4 is a hydrogen atom or a hydroxyl group, or
a pharmaceutically acceptable salt thereof;
at least one water-insoluble or hardly water-soluble substance selected from the group consisting of a low substituted hydroxypropylcellulose, a partly pregelatinized starch, crospovidone, croscarmellose sodium, carmellose calcium, hydroxypropyl starch, myristic acid, lauric acid, palmitic acid, saccharin and cholesterol; and
a silicone biocompatible hydrophobic polymer.
2. The sustained-release formulation of claim 1 , wherein the at least one water-insoluble or hardly water-soluble substance is low substituted hydroxypropylcellulose and/or cholesterol.
3. The sustained-release formulation of claim 1 , wherein the solid sustained-release formulation has the solid sheet or rod shape and is suitable for placement in the vicinity of a spinal cord injury site or in a spinal cavity.
4. The sustained-release formulation of claim 1 , wherein the solid sustained-release formulation has the sheet shape and a thickness of 0.1 to 1.5 mm.
5. The sustained-release formulation of claim 1 , wherein the formulation comprises the water-insoluble or hardly water-soluble substance in 3 to 35% by weight per 100% by weight of the whole formulation.
6. The sustained-release formulation of claim 1 , wherein the formulation comprises the silicone in 55% or more by weight per 100% by weight of the whole formulation.
7. The sustained-release formulation of claim 1 , further comprising a water-soluble additive agent.
8. The sustained-release formulation of claim 7 , wherein the water-soluble additive agent is at least one selected from the group consisting of sodium chloride, glucose, mannitol, lactose, glycine, sodium cholate, sodium glycocholate and sodium desoxycholate.
9. The sustained-release formulation of claim 7 , wherein the water-soluble additive agent is at least one selected from the group consisting of sodium chloride and sodium desoxycholate.
10. The sustained-release formulation of claim 9 , wherein the water-insoluble or hardly water-soluble substance is low substituted hydroxypropylcellulose, and the water-soluble additive agent is sodium chloride.
11. The sustained-release formulation of claim 9 , wherein the hardly water-soluble substance is cholesterol, and the water-soluble additive agent is sodium desoxycholate.
12. The sustained-release formulation of claim 9 wherein the hardly water-soluble substance is cholesterol.
13. The sustained-release formulation of claim 1 , comprising 10 to 40% by weight of
(i) the compound of Formula (1) or pharmaceutically acceptable salt thereof,
(ii) the at least one water-insoluble or hardly water-soluble substance, and
(iii) an optional water-soluble additive agent
per 100% by weight of the whole formulation,
provided that the total weight of the compound of Formula (1) or pharmaceutically acceptable salt thereof and the optional water-soluble additive agent is not more than 35% per 100% by weight of the whole formulation.
14. The sustained-release formulation of claim 1 , wherein the compound of Formula (1) or pharmaceutically acceptable salt thereof is contained in an amount of 3 to 350 μg per 1 mg of the formulation.
15. The sustained-release formulation of claim 1 , which is a matrix formulation.
16. The sustained-release formulation of claim 1 , wherein R 1 and R 3 are each a carboxyl group, and R 2 and R 4 are each a hydroxyl group.
17. A sustained-release formulation having a solid sheet or rod shape consisting essentially of:
a compound of Formula (1):
wherein R 1 is a hydrogen atom or a carboxyl group, R 2 is a hydrogen atom or a hydroxyl group, R 3 is a hydrogen atom or a carboxyl group, and R 4 is a hydrogen atom or a hydroxyl group, or
a pharmaceutically acceptable salt thereof;
at least one water-insoluble or hardly water-soluble substance selected from the group consisting of a low substituted hydroxypropylcellulose, a partly pregelatinized starch, crospovidone, croscarmellose sodium, carmellose calcium, hydroxypropyl starch, myristic acid, lauric acid, palmitic acid, saccharin and cholesterol;
a silicone biocompatible hydrophobic polymer; and
optionally a water-soluble additive agent.