Methotrexate transdermal local controlled release preparation and its preparation method and application

A technology of methotrexate and controlled-release preparations, which is applied in pharmaceutical formulations, antipyretics, anti-inflammatory agents, etc., can solve problems such as adverse reactions of patients, reduce the dosage of patients, achieve convenient storage and management of medicines, and improve light Stability, the effect of ensuring photostability

Active Publication Date: 2022-03-15
BEIJING UNIV OF AGRI
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0003] The problem to be solved by the present invention is that the content of methotrexate preparations is reduced due to light and the generation of analogues, and the adverse reactions of patients caused by long-term large-scale administration can effectively reduce the dosage of patients.

Method used

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  • Methotrexate transdermal local controlled release preparation and its preparation method and application
  • Methotrexate transdermal local controlled release preparation and its preparation method and application
  • Methotrexate transdermal local controlled release preparation and its preparation method and application

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0047] The preparation of embodiment 1 mesoporous silica

[0048]Add 24mL of cetyltrimethylammonium chloride (CTAC), 36mL of water, and 0.18g of triethanolamine (TEA) into a 100mL flask in sequence, and stir magnetically at a constant temperature of 80°C for 1h. The prepared mixture of 4 mL tetraethyl orthosilicate (TEOS) and 1 mL cycloethane was added dropwise and stirred slowly at 60° C. for 12 h. After the reaction is completed, wash with 0.6% ammonium nitrate ethanol solution three times in a 60° C. water bath, each time for 6 hours. After the reaction was completed, the ammonium nitrate was removed with absolute ethanol, and freeze-dried to obtain mesoporous silica. Characterization diagram of mesoporous silica Figure 1a and Figure 1b , Figure 1c , Figure 1d .

Embodiment 2

[0049] Embodiment 2. Methotrexate content assay method

[0050] (1) Chromatographic conditions

[0051] Use Shimadzu LC-6AD to detect methotrexate content, chromatographic column: Thermo ODS-2 C18 (150mm×4.6mm, 5μm), mobile phase is acetonitrile: water=17:83 (0.1% trifluoroacetic acid), detection Wavelength: 302nm, flow rate: 1ml / min, injection volume 20μl. Chromatographic column: SinoPak C18 5 μm. Column size: 4.6mm*200mm.

[0052] (2) Draw a standard curve

[0053] Dilute the previously prepared 110μg / ml MTX standard solution with distilled water to make solutions of 2.2μg / ml, 5.5μg / ml, 11μg / ml, 22μg / ml, 55μg / ml and 110μg / ml respectively, each concentration Inject once, each injection volume is 20 μl. Take the peak area as the ordinate, and the concentration of the standard solution as the abscissa, and perform linear regression.

[0054] (3) Sample processing method

[0055] Measure different concentrations of methotrexate with high performance liquid chromatography,...

Embodiment 3

[0056] Example 3. Stability study of methotrexate

[0057] The effects of light time, different pH values ​​(5.5, 7.4, 8.5, 9.0), and temperature (25°C, 40°C, 80°C) on the stability of methotrexate were compared.

[0058] (1) Light stability: Take 6 small centrifuge tubes, mark them, and add 1ml of each (110μg / ml, pH7.4) methotrexate solution into them with a pipette gun, and wrap the dark group completely with tinfoil To avoid light conditions. The two groups were placed under sunlight at the same time, and samples were taken at 6h, 24h, 48h, 96h, and 144h respectively.

[0059] (2) Temperature stability: Take 9 small centrifuge tubes, add 1ml of each (110μg / ml, pH 7.4) methotrexate solution into them with a pipette gun after marking, and store them in different temperatures (25°C) in the dark. , 40°C, 80°C), and samples were taken at 6h, 24h, 48h, 72h, and 96h.

[0060] (3) pH stability: Take 12 small centrifuge tubes, add pre-prepared methotrexate solutions with differen...

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Abstract

The invention discloses a local controlled-release preparation of methotrexate for transdermal administration and its preparation method and application. The preparation is that mesoporous silicon dioxide is loaded with methotrexate, and the surface is coated with a layer of polydopamine or polymethyldopa . The mesoporous silica used has good biocompatibility, large specific surface area, and high drug loading capacity. Polydopamine is polymerized under alkaline conditions, and the drug is encapsulated in mesoporous silica, which can be released under acidic conditions. Methotrexate, to achieve the purpose of controlled drug release. The outer surface of the preparation is coated with a layer of black polydopamine, which can also ensure the photostability of methotrexate, and is more convenient in the process of medicine storage and management. At the same time, the study found that polymethyldopa exhibited a "gate control" effect similar to polydopamine, and intelligently delivered drugs.

Description

technical field [0001] The invention relates to the field of drug controlled release, in particular to a methotrexate transdermal local controlled release preparation and its preparation method and application, using mesoporous silicon dioxide to load methotrexate, polydopamine or methyldopa After encapsulation, the light stability of methotrexate is improved to realize the controllable release of methotrexate. Background technique [0002] Rheumatoid arthritis (RA) is an autoimmune disease mainly characterized by joint synovial inflammation and involving the whole body. Methotrexate (MTX), as the core drug of choice for the treatment of rheumatoid arthritis, can regulate the abnormal immunity of patients, significantly reduce cartilage destruction and bone erosion, control the aggravation of bone lesions, prevent or delay joint destruction, and reduce disability. It plays an important role in the treatment of controlling the progression of the disease. However, long-term ...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K47/69A61K47/59A61K31/519A61P19/02A61P29/00A61P35/00
CPCA61K31/519A61K47/6923A61K47/59A61K9/0014A61P19/02A61P29/00A61P35/00
Inventor 常明明郭婷婷康旭
Owner BEIJING UNIV OF AGRI
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