Cationic adhesion type mycophenolate mofetil nano eye drop

Abstract

The invention relates to a cationic adhesion type mycophenolate mofetil nano eye drop, which comprises mycophenolate mofetil of which the mass percentage concentration is 1 percent, proper amount of osmotic pressure modifying agent and pH modifying agent. The eye drop is characterized in that the eye drop also comprises chitosan, Pluronic F-68 and phospholipid, wherein the mass percentage concentration of the phospholipids in the eye drop is between 0.2 and 2 percent; the mass percentage concentration of the Pluronic F-68 in the eye drop is between 0.5 and 4 percent; the mass percentage concentration of the chitosan in the eye drop is between 0.5 and 4 percent; the molecular weight of the chitosan is between 5,000 and 300,000; the deacetylation degree is more than 85 percent; and the grain diameter of the mycophenolate mofetil is between 10 and 700 nm. The eye drop has the characteristics that: the mycophenolate mofetil with nanometer grain diameter improves the medicament solubility,the safety and the effectiveness; mycophenolate mofetil medicament particles are charged with positive charges so as to be favorable for improving the cornea absorption of the medicament, improving the medicament effect, prolonging the medicament duration, and greatly improving the cornea adhesion.

Description

[0001] The invention relates to a mycophenolate mofetil eye drop, in particular to a cationic adhesion type mycophenolate mofetil nanometer eye drop. Background technique

[0002] Among the blinding eye diseases in our country, corneal disease ranks second only to cataract. Currently, corneal transplant rejection is the leading cause of transplant failure. In avascular implant beds, the incidence of rejection is 5-10%, while in high-risk corneal transplants, the incidence of rejection can be as high as 65%. How to effectively prevent and treat immune rejection after penetrating keratoplasty and improve the survival rate of grafts has become one of the focuses of research by ophthalmologists.

[0003] Mycophenolate mofetil (MMF) is an effective anti-immune rejection drug, but currently only oral preparations are available. Adverse reactions are serious after oral systemic administration. It has been reported in the literature that 18% of patients receiving mycophenolate mofet...

Examples

Embodiment 1

[0020] 0.3g mycophenolate mofetil and 60mg phospholipids were dissolved in 50ml ether, and the ether was fully removed by rotary evaporation to obtain a uniformly dispersed film of medicine and phospholipids, and then 2% chitosan (molecular weight 5000, deacetylation degree 85%) solution 7.5 ml and 7.5ml of 2% F-68 solution, fully wash the membrane, and obtain an emulsion after ultrasonic dispersion, pass the emulsion through a high-pressure homogenizer, first use a pressure of 500bar to circulate 5 times for initial crushing, and then use a pressure of 1500bar to circulate 15 times Further refine and pulverize, then dilute the homogeneous emulsion to 30ml with water for injection, adjust the osmotic pressure to isotonicity with sodium chloride, and dilute the pH value of hydrochloric acid to 6.5 to obtain cationic adhesion type mycophenolate mofetil nanosuspension drops eye drops.

[0021] The particle size range of the nanosuspension measured by the laser particle size poten...

Embodiment 2

[0023] Dissolve 0.3g of mycophenolate mofetil and 0.6g of phospholipid in 50ml of ether, and remove the ether by rotary evaporation to obtain a uniformly dispersed film of medicine and phospholipid, then add 1.2g of chitosan and F -681.2g was dissolved in 25ml of water for injection and fully dissolved, the film was fully washed with the solution of chitosan and F-68, and the emulsion was obtained after ultrasonic dispersion, and the emulsion was passed through a high-pressure homogenizer, and the pressure was circulated for 5 times at 500bar. First pulverize, then use 1500bar pressure to cycle 15 times for further fine pulverization, then dilute the homogeneous emulsion to 30ml with water for injection, adjust the osmotic pressure to isotonic with sodium chloride, and dilute the pH value of hydrochloric acid to 6.5 to obtain cations Adhesive mycophenolate mofetil nanosuspension eye drops. The particle size range of the nanosuspension measured by the laser particle size potent...

Embodiment 3

[0025] The present invention can also be obtained by replacing the chitosan in Example 1 with a chitosan with a molecular weight of 300,000 and a deacetylation degree of 85%. The particle size range of the nanosuspension measured by the optical particle size potential analyzer is 100-700nm, the average particle size is 427nm, and the particle surface potential is +49mV. The obtained nanosuspension was stored at 4° C. for 6 months without light, and the particle size and potential did not change substantially.

[0001] The invention relates to a mycophenolate mofetil eye drop, in particular to a cationic adhesion type mycophenolate mofetil nanometer eye drop. Background technique

[0002] Among the blinding eye diseases in our country, corneal disease ranks second only to cataract. Currently, corneal transplant rejection is the leading cause of transplant failure. In avascular implant beds, the incidence of rejection is 5-10%, while in high-risk corneal transplants, the incidence of rejection can be as high as 65%. How to effectively prevent and treat immune rejection after penetrating keratoplasty and improve the survival rate of grafts has become one of the focuses of research by ophthalmologists.

[0003] Mycophenolate mofetil (MMF) is an effective anti-immune rejection drug, but currently only oral preparations are available. Adverse reactions are serious after oral systemic administration. It has been reported in the literature that 18% of patients receiving mycophenolate mofet...

Examples

Embodiment 1

[0020] 0.3g mycophenolate mofetil and 60mg phospholipids were dissolved in 50ml ether, and the ether was fully removed by rotary evaporation to obtain a uniformly dispersed film of medicine and phospholipids, and then 2% chitosan (molecular weight 5000, deacetylation degree 85%) solution 7.5 ml and 7.5ml of 2% F-68 solution, fully wash the membrane, and obtain an emulsion after ultrasonic dispersion, pass the emulsion through a high-pressure homogenizer, first use a pressure of 500bar to circulate 5 times for initial crushing, and then use a pressure of 1500bar to circulate 15 times Further refine and pulverize, then dilute the homogeneous emulsion to 30ml with water for injection, adjust the osmotic pressure to isotonicity with sodium chloride, and dilute the pH value of hydrochloric acid to 6.5 to obtain cationic adhesion type mycophenolate mofetil nanosuspension drops eye drops.

[0021] The particle size range of the nanosuspension measured by the laser particle size poten...

Embodiment 2

[0023] Dissolve 0.3g of mycophenolate mofetil and 0.6g of phospholipid in 50ml of ether, and remove the ether by rotary evaporation to obtain a uniformly dispersed film of medicine and phospholipid, then add 1.2g of chitosan and F -681.2g was dissolved in 25ml of water for injection and fully dissolved, the film was fully washed with the solution of chitosan and F-68, and the emulsion was obtained after ultrasonic dispersion, and the emulsion was passed through a high-pressure homogenizer, and the pressure was circulated for 5 times at 500bar. First pulverize, then use 1500bar pressure to cycle 15 times for further fine pulverization, then dilute the homogeneous emulsion to 30ml with water for injection, adjust the osmotic pressure to isotonic with sodium chloride, and dilute the pH value of hydrochloric acid to 6.5 to obtain cations Adhesive mycophenolate mofetil nanosuspension eye drops. The particle size range of the nanosuspension measured by the laser particle size potent...

Embodiment 3

[0025] The present invention can also be obtained by replacing the chitosan in Example 1 with a chitosan with a molecular weight of 300,000 and a deacetylation degree of 85%. The particle size range of the nanosuspension measured by the optical particle size potential analyzer is 100-700nm, the average particle size is 427nm, and the particle surface potential is +49mV. The obtained nanosuspension was stored at 4° C. for 6 months without light, and the particle size and potential did not change substantially.

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