Preparation method of methotrexate and alendronate sodium conjugate

A technology of sodium alendronate and methotrexate, applied in chemical instruments and methods, medical preparations of non-active ingredients, drug combinations, etc., can solve problems such as complicated process production, cumbersome operation requirements, and inability to produce on a large scale

Active Publication Date: 2017-09-26
YANGZHOU UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

The invention provides a pharmaceutical composition containing methotrexate to increase the targeting of the drug. However, these existing technologies have problems such as high cost of raw materials, complicated process manufacturing, and cumbersome operation requirements, so they cannot be mass-produced

Method used

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  • Preparation method of methotrexate and alendronate sodium conjugate
  • Preparation method of methotrexate and alendronate sodium conjugate
  • Preparation method of methotrexate and alendronate sodium conjugate

Examples

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example 1

[0033] Weigh 3.6 g of methotrexate with 90 ml of ultrapure water and mix it with an electronic balance, add dropwise acetone until the methotrexate is basically dissolved to form a methotrexate solution.

[0034] To the methotrexate solution, add 3 g of 2-morpholineethanesulfonic acid (MES), 1.8 g of N-hydroxysuccinimide (NHS), 3 g of 1-(3-dimethylamino)-3- Ethylcarbodiimide hydrochloride (EDC).

[0035] Then add 6 g of alendronate sodium, place it on a magnetic stirrer, and continue to stir and react for 3 hours.

[0036] After the reaction, the obtained solution was poured into a 300 molecular weight dialysis bag, and placed in a large beaker filled with ultrapure water for dialysis for 24 h, and the ultrapure water was changed every 2-6 h.

[0037] After the dialysis is finished, take out the material in the dialysis bag, freeze the taken out material in an open container and wrap it with a plastic wrap, then punch and dry for 48 hours to obtain the desired target product....

example 2

[0039] Weigh 7.2g of methotrexate with an electronic balance and mix it with 180ml of ultrapure water, add dropwise chloroform until the methotrexate is basically dissolved to form a methotrexate solution.

[0040] Add 6 g of 2-morpholineethanesulfonic acid (MES), 3.6 g of N-hydroxysuccinimide (NHS), 6 g of 1-(3-dimethylamino)-3 to the forming methotrexate solution - Ethylcarbodiimide hydrochloride (EDC).

[0041] Then add 12 g of alendronate sodium, place it on a magnetic stirrer, and continue to stir and react for 12 hours.

[0042] After the reaction, the obtained solution was poured into a 600 molecular weight dialysis bag, and placed in a large beaker filled with ultrapure water for dialysis for 24 h, and the ultrapure water was changed every 2-6 h.

[0043] After the dialysis is finished, take out the material in the dialysis bag, freeze the taken out material in an open container and wrap it with a plastic wrap, then punch and dry for 72 hours to obtain the desired tar...

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Abstract

The invention discloses a preparation method of a methotrexate and alendronate sodium conjugate, and belongs to the technical field of organic pharmaceutical production. The method comprises the following steps: mixing the methotrexate, ultra-pure water and an organic solvent to obtain a methotrexate solution; then adding morpholineethanesulfonic acid, N-hydroxysuccinimide, 1-(3-dimethylamino)-3-ethylcarbodiimide hydrochloride into the methotrexate solution to obtain a methotrexate mixed solution; mixing the methotrexate mixed solution with alendronate sodium for reaction under a magnetic force stirring effect; carrying out dialysis and lyophilization to obtain a nanoscale methotrexate and alendronate sodium conjugate. By adopting the conjugate, a novel targeting medicine for orthopedics can be obtained, so that the medicine can be enriched toward lesions of orthopedics, and a preferable treatment effect can be achieved.

Description

technical field [0001] The invention belongs to the technical field of organic pharmaceutical production. Background technique [0002] Methotrexate (4-amino-10-methylfolate, abbreviated: MTX) is a folic acid analogue that was first used in the treatment of rheumatoid arthritis (RA) in 1988. The combination of methotrexate and biologics such as adalimumab can more effectively relieve disease symptoms in RA patients, slow down the progression of joint damage (shown by X-rays), and improve physical function. Compared with traditional drugs, biologics such as adalimumab have strong and long-lasting efficacy and are well tolerated. [0003] Alendronate Sodium (abbreviation: ALN) was listed in the United States under the name of Fosamax in 1995, for the treatment of osteoporosis and osteitis deformans. In May 1997, the FDA re-approved its prevention of osteoporosis and prevention of fracture expansion. Indications, becoming the first non-hormonal drug approved by the FDA for th...

Claims

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Application Information

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IPC IPC(8): C07F9/6561A61K47/55A61P19/02A61P29/00
CPCC07F9/6561
Inventor 朱沛志赵科王进宇刘冠雄
Owner YANGZHOU UNIV
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