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Methotrexate chitosan thermosensitive gel and its application

A technology of methotrexate shell and temperature-sensitive gel is applied in the directions of non-active ingredients medical preparations, active ingredients-containing medical preparations, organic active ingredients, etc. The effect of quality, controllable quality and stable nature

Active Publication Date: 2016-01-13
CHANGSHA JINGYI PHARM TECH CO LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

These side effects limit the clinical maximum dose of MTX

Method used

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  • Methotrexate chitosan thermosensitive gel and its application
  • Methotrexate chitosan thermosensitive gel and its application
  • Methotrexate chitosan thermosensitive gel and its application

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0050] The construction of embodiment 1 methotrexate-chitosan thermosensitive gel

[0051] 1 Method and results

[0052] 1.1 Solution preparation

[0053] Raw materials and dosage:

[0054]

[0055] 1.1.1 Chitosan solution

[0056] Weigh the prescribed amount of CS, add an appropriate amount of water, stir magnetically to form a CS suspension, then add the prescribed amount of acidic solvent drop by drop, and continue stirring to completely dissolve the CS to obtain a CS solution.

[0057] 1.1.2 Disodium glycerophosphate solution

[0058] Weigh the prescribed amount of GP, add appropriate amount of water, and ultrasonically dissolve to obtain the GP solution.

[0059] 1.1.3 Methotrexate solution

[0060] Weigh the prescribed amount of MTX and other excipients (NaOH, solubilizer, isotonicity regulator), add appropriate amount of water, and ultrasonically dissolve to obtain the MTX solution.

[0061] The above-prepared solution was stored at 4°C for future use.

[0062...

Embodiment 2

[0133] Example 2 Methotrexate Chitosan Thermosensitive Gel Formulation Properties Research

[0134] 1 Method and results

[0135] 1.1 Appearance

[0136] CS / GP / MTXsol is a light yellow transparent solution, no insoluble components or massive agglomerates can be seen by naked eyes. CS / GP / MTXsol was gelled in a 37°C water bath to obtain CS / GP / MTXgel, which was in the form of light yellow semi-solid.

[0137] 1.2 Microstructure of the gel

[0138] After the CS / GP / MTXgel sample was freeze-dried for 24 hours, it was snapped off by liquid nitrogen quenching, and its cross-section was vacuum-sprayed with gold. The internal structure of CS / GP / MTXgel was characterized by SEM. It can be seen from Figure 1 that the internal structure of CS / GP / MTXgel is irregular and porous.

[0139] 1.3 Viscosity, gel time and pH value

[0140] Prepare 3 batches of CS / GP / MTXsol according to the optimized prescription, and measure their t gel , η and pH value, see Table 2-1. The results show that t...

Embodiment 3

[0190] Example 3 Pharmacokinetics of Methotrexate Chitosan Thermosensitive Gel in Rabbits

[0191] 1.1 Experimental animals

[0192] Healthy male New Zealand white rabbits (1.8-2.5Kg), license number: SCXK (Xiang) 2009-0012, Changsha Tianqin Biotechnology Co., Ltd.

[0193] 2 Methods and results

[0194] 2.1 Reagent

[0195] 2.1.1 Preparation of CS / GP / MTXsol

[0196] With embodiment 1.

[0197] 2.1.2 Preparation of methotrexate injection

[0198] Weigh an appropriate amount of NaOH, and prepare a concentration of 0.198mol L with 0.9% NaCl solution -1 NaOH saline solution. Use NaOH physiological saline solution to prepare a concentration of 50mg·mL -1 MTX injection.

[0199] 2.2 Experimental scheme

[0200] Twelve New Zealand white rabbits were randomly divided into two groups (n=6), namely the experimental group and the control group. According to 5mg·kg -1 Subcutaneous injection on the back, the experimental group was injected with CS / GP / MTXsol, and the control gro...

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Abstract

The invention provides MTX subcutaneous sustained-release injection CS / GP / MAX (Methotrexate-loaded Chitosan-based Thermosensitive Hydrogel). Every liter of aqueous solution of the CS / GP / MAX contains 16 to 22 grams of chitosan, 0.05 to 0.1 mole of acetic acid, 70 to 150 grams of beta-glycerophosphate, 0.1 to 0.12 mole of methotrexate, 0.1 to 0.12 mole of a solubilizer and 5 to 50 grams of an isoosmotic adjusting agent and pH modifier. The CS / GP / MAX has stable properties and controllable quality, and the external properties, tgel (the time of gelation), eta, pH value, content and preliminary stability of the CS / GP / MAX meet requirements on thermosensitive hydrogel; 70 percent of drugs of the CS / GP / MAX in a PBS (Phosphate Buffer Solution) are released within 5 days under the condition of 37 DEG C; compared with those of MTX injection, the Cmax (Maximum Plasma Drug Concentration) is reduced by 82 percent, the AUC0-t (area under the plasma concentration time curve from time 0 to t hours) is enlarged by 2.37 times, and the t0.02muM (the length of time the MTX concentration-time curve remained above 0.02 muM in one week) is prolonged by 12.93 times after the CS / GP / MAX is subcutaneously injected to the back of a rabbit; by the CS / GP / MAX, adverse effects can be reduced, and curative effects can be improved.

Description

technical field [0001] The invention belongs to the field of pharmaceutical preparations, and in particular relates to a methotrexate-chitosan temperature-sensitive gel and its application. Background technique [0002] Rheumatoid Arthritis (Rheumatoid Arthritis, RA) is a chronic autoimmune disease of unknown etiology. It has a high disability rate, seriously affects the working ability and daily life of patients, and imposes a heavy burden on patients and society. [0003] Methotrexate (MTX, structural formula see Formula 1) is the anchor drug (anchordrug) for the treatment of RA, that is, when the patient is diagnosed and needs medication, if there are no contraindications, MTX should be considered; when the patient’s condition is under control, And when starting to gradually reduce the drug, if no MTX-related side effects occur, other drugs should be reduced first, and MTX should be reduced and withdrawn last. At present, the mechanism of MTX as a treatment for RA is not...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K9/08A61K9/06A61K31/519A61K47/36A61P29/00A61P19/02
Inventor 梁丰田娟王婷
Owner CHANGSHA JINGYI PHARM TECH CO LTD
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