Preparation method of leuprorelin microspheres

A technology of leuprolide and microspheres, which is applied in the field of preparation of leuprolide microspheres, can solve the problems of easy boiling and volatilization, and achieve the effects of stable colostrum, reduced residue, and smooth production

Active Publication Date: 2017-05-17
ZHEJIANG SUNDOC PHARMA SCI & TECH CO LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0005] The purpose of the present invention is to solve the above-mentioned problems existing in the prior art, and to provide a preparation method of leuprolide microspheres, which adopts fully enclosed on-line emulsification and drying in separate tanks, and through precise control of temperature and pressure, thereby It effectively solves the problem of easy volatilization and boiling of DCM in the emulsification process, and improves the emulsification efficiency by reducing the viscosity of the oil phase, reduces the residue of colostrum in the tank, and improves the overall yield of the product

Method used

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  • Preparation method of leuprorelin microspheres
  • Preparation method of leuprorelin microspheres
  • Preparation method of leuprorelin microspheres

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0035] Oil phase: prepare 675g (about 7650 sticks) of 37.5% PLG DCM solution in a closed oil phase tank (material: 316L, pressure resistance: -5~25bar, the same below), and control 1 bar in the tank by nitrogen or compressed air Pressure, keep at room temperature, set aside.

[0036] Inner water phase: Add 29g of leuprolide raw material into the inner water phase tank to prepare 43.7% leuprolide aqueous solution for use.

[0037] External water phase: Prepare 32L of 0.1% PVA solution in the external water phase tank, then cool down to 4°C, and set aside.

[0038] Preparation of colostrum: Open the bottom valve of the oil phase tank, turn on the online shearer 1 (IKA DRS2000 / 03), adjust the speed to 5000rpm, and pump a small amount of oil phase into the shearer to fill it up, so that the shearer is mixed with oil Balance the pressure of the phase tank (up to 1 bar), then adjust the pump speed, mix the oil phase and the inner water phase at a ratio of 10:1, pump it into the onl...

Embodiment 2

[0042] Oil phase: prepare 675g (about 7650 sticks) of 37.5% PLG DCM solution in a closed oil phase tank, control the pressure of 10bar in the tank by nitrogen or compressed air, heat to 100°C, and set aside.

[0043] Inner water phase: Add 29g of leuprolide raw material into the inner water phase tank to prepare 43.7% leuprolide aqueous solution for use.

[0044] External water phase: prepare 32L of 0.1% PVA solution in the external water phase tank, then cool down to 20°C, and set aside.

[0045] Preparation of colostrum: Open the bottom valve of the oil phase tank, turn on the online shearer 1 (IKA DRS2000 / 03), adjust the speed to 15000rpm, and pump a small amount of oil phase into the shearer to fill it up, so that the shearer is mixed with oil Balance the pressure of the phase tank (up to 10bar), then adjust the pump speed, mix the oil phase and the inner water phase at a ratio of 10:1, pump it into the online shearer, open the corresponding valve group, and let the sheare...

Embodiment 3

[0049] Oil phase: prepare 2700g of 37.5% PLG DCM solution (about 30,500 sticks) in a closed oil phase tank, control the pressure of 2.5bar in the tank with nitrogen or compressed air, heat to 40°C, and set aside.

[0050] Inner water phase: add 116g of leuprolide raw material into the inner water phase tank to prepare 43.7% leuprolide aqueous solution for use.

[0051] External water phase: Prepare 128L of 0.1% PVA solution in the external water phase tank, then cool down to 17°C and set aside.

[0052] Preparation of colostrum: Open the bottom valve of the oil phase tank, turn on the online shearer 1 (IKA DRS2000 / 03), adjust the speed to 20000rpm, and pump a small amount of oil phase into the shearer to fill it up, so that the shearer is mixed with oil Balance the pressure of the phase tank (up to 2.5bar), then adjust the pump speed, mix the oil phase and the inner water phase according to the ratio of 10:1, pump it into the online shearer, open the corresponding valve group,...

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Abstract

The invention discloses a preparation method of leuprorelin microspheres. The method comprises steps of preparation of an oil phase, preparation of an inner water phase, preparation of an outer water phase, preparation of a primary emulsion, preparation of a compound emulsion, drying in a liquid and the like. A total-closed online emulsification and separate tank drying mode is adopted, and the problems of high probability of evaporation and boiling of DCM in the emulsification process are effectively solved by accurately controlling temperatures and pressure; through reduction of the viscosity of the oil phase, the emulsification efficiency is improved, residues of the primary emulsion in tanks are reduced, and the overall yield of a product is increased. Besides, batch production of the leuprorelin microspheres is changed into continuous production, transition from a lab-scale test to a pilot plant test to production is smoother, and room for improvement of the productivity of a workshop is larger.

Description

technical field [0001] The invention relates to the technical field of slow-release medicine production, in particular to a preparation method of leuprolide microspheres. Background technique [0002] Conventional preparation methods of microspheres include double emulsion method, phase separation method, spray drying method and hot-melt extrusion method, among which the most classic preparation method is double emulsion method. [0003] The double emulsion method is to dissolve biodegradable polymer materials (hereinafter referred to as polymers) in organic solvents to obtain oil phases, dissolve water-soluble raw materials in water to obtain internal water phases, and emulsify the two phases to obtain colostrum ( w / o, water-in-oil emulsion). Then add the colostrum into the external water phase, and emulsify again to obtain double emulsion (w / o / w, water-in-oil-in-water emulsion). Then, the organic solvent is removed by drying in liquid to obtain drug-loaded microspheres, ...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K38/09A61K9/16A61P15/00A61P35/00
CPCA61K9/1647A61K9/1682A61K38/09
Inventor 丁多浩张鸿夏典蓉
Owner ZHEJIANG SUNDOC PHARMA SCI & TECH CO LTD
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