Silybin injection and preparation method therefor
A silybin injection contains silybin, sulfobutyl ether-β-cyclodextrin, an organic solvent for injection, a pH regulator, and may further contain a co-solvent, a lyophilization bulking agent, and water for injection.
1. A composition, comprising silybin, sulfobutylether-β-cyclodextrin, an organic solvent for injection, and a pH regulator, wherein the pH regulator is not NaOH and HCl.
2. The composition of claim 1 , further comprising a cosolvent selected from one or more of distearoyl phosphatidylethanolamine-polyethylene glycol 2000, distearoyl phosphatidylethanolamine-polyethylene glycol 5000, polysorbate 80, polyoxyl hydrogenated castor oil, and poly(ethylene glycol)-block-poly(propylene glycol)-block-poly(ethylene glycol).
3. The composition of claim 1 , comprising the following components by weight/volume percentage:
silybin
0.05-1.0%
sulfobutylether-β-cyclodextrin
2-50%
organic solvent for injection
0.5-10%
cosolvent
0-1.0%
bulking agent
0-20%
pH regulator
regulating the pH value to be 2.0-8.0
water for injection
the balance.
4. The composition of claim 3 , comprising the following components by weight/volume percentage:
Silybin
0.1-0.8%
sulfobutylether-β-cyclodextrin
2-30%
organic solvent for injection
0.5-5%
cosolvent
0.001-0.5%
bulking agent
0-15%
pH regulator
regulating the pH value to be 2.0-7.0
water for injection
the balance.
5. The composition-of claim 4 , comprising the following components by weight/volume percentage:
Silybin
0.1-0.5%
sulfobutylether-β-cyclodextrin
2-10%
organic solvent for injection
1-5%
cosolvent
0.005-0.5%
bulking agent
3-10%
pH regulator
regulating the pH value to be 2.5-6.0
water for injection
the balance.
6. The composition of claim 1 , wherein the organic solvent for injection is selected from one or more of polyethylene glycol 200, polyethylene glycol 300, polyethylene glycol 400, polyethylene glycol 600, and propylene glycol.
7. The composition of claim 3 , wherein the bulking agent is selected from one or more of mannitol, lactose, dextran 20, dextran 40, dextran 70, sucrose, xylitol, sorbitol and trehalose.
8. The composition of claim 1 , wherein the pH regulator is selected from one or more of citric acid, hydrochloric acid, glacial acetic acid, phosphoric acid, disodium hydrogen phosphate, sodium dihydrogen phosphate, dipotassium hydrogen phosphate, monopotassium phosphate, disodium citrate, trisodium citrate and sodium acetate, wherein the pH regulator regulates at pH 2 to 8.
9. The composition of claim 1 , in the form of a silybin solution suitable for injection.
10. A method of preparing the composition of claim 9 comprising: mixing silybin and the organic solvent for injection, and heating and stirring the mixture at 40° C. to 70° C. to obtain an organic phase; mixing the sulfobutylether-β-cyclodextrin and water to obtain an aqueous phase; mixing the organic phase with the aqueous phase to obtain a medicine solution; adding the pH regulator to regulate the pH value of the medicine solution to be pH 2 to 8; treating the medicine solution with 0.05 w/v %-0.5 w/v % activated carbon, filtering the solution through a 1 μm titanium rod, and then through a 0.22 μm filter.
11. The composition of claim 1 , in the form of freeze-dried preparation for injection, wherein the organic solvent for injection is selected from polyethylene glycol or propylene glycol.
12. A method of preparing the composition of claim 11 comprising: mixing silybin and the organic solvent for injection, and heating and stirring the mixture at 40° C. to 70° C. to obtain an organic phase; mixing sulfobutylether-β-cyclodextrin, a bulking agent, and to obtain an aqueous phase; mixing the organic phase with the aqueous phase to obtain a medicine solution; adding a pH regulator to regulate the pH value of the medicine solution to be pH 2 to 8; treating the medicine solution with 0.05 w/v %-0.5 w/v % activated carbon filtering the solution through a 1 μm titanium rod, filtering through a 0.22 μm filter; and performing sub-packaging, freeze-drying and sealing.
13. The composition of claim 6 , wherein the organic solvent for injection is polyethylene glycol 400.
14. The composition of claim 2 , wherein the cosolvent is distearoyl phosphatidylethanolamine-polyethylene glycol 2000.
15. The composition of claim 7 , wherein the bulking agent is mannitol, lactose, or dextran 40.
16. The composition of claim 8 , wherein the pH regulator regulates at pH 2.0 to 7.0.
17. The composition of claim 16 , wherein the pH regulator regulates at pH 2.5 to 6.0.
18. The method of claim 10 , further comprising a step of adding a cosolvent to the organic phase, wherein the cosolvent is selected from one or more of distearoyl phosphatidylethanolamine-polyethylene glycol 2000, distearoyl phosphatidylethanolamine-polyethylene glycol 5000, polysorbate 80, polyoxyl hydrogenated castor oil, and poly(ethylene glycol)-block-poly(propylene glycol)-block-poly(ethylene glycol).
19. The method of claim 12 , further comprising a step of adding a cosolvent to the organic phase, wherein the cosolvent is selected from one or more of distearoyl phosphatidylethanolamine-polyethylene glycol 2000, distearoyl phosphatidylethanolamine-polyethylene glycol 5000, polysorbate 80, polyoxyl hydrogenated castor oil, and poly(ethylene glycol)-block-poly(propylene glycol)-block-poly(ethylene glycol).