Gelatin-chitosan/montmorillonite drug carried microspheres and preparation method thereof

Abstract

The invention discloses a gelatin-chitosan / montmorillonite drug carried microsphere and a preparation method thereof. The drug carried microsphere is prepared by the following steps: dissolving the hydrophilic drug in the gelatin water solution, adding montmorillonite suspended water solution, carrying out intercalation reaction to obtain solution A; dissolving the chitosan in the acetic acid water solution, stirring and dissolving to obtain solution B; stirring and emulsifying liquid paraffin wax and span-80 to obtain C; adding solution B into solution A, carrying out intercalation reaction, adding C, stirring, standing, dropwise adding glutaric dialdehyde water solution, crosslinking and curing, adding isopropyl alcohol and stirring, removing supernate after standing and delaminating, vacuum filtrating to remove liquid; and washing with anhydrous ether and isopropyl alcohol in sequence, and drying to obtain the microsphere. The drug carried microsphere in the invention has good tissue compatibility, low toxicity or no toxicity, and is a drug carried material with excellent performance. The method in the invention can reduce the dosage of chemical crosslinking agent, lower the toxity of the microsphere, dramatically lower the rate of drug release, and further improve slowly controlled release ability of the drugs.

Description

technical field

[0001] The invention belongs to the field of pharmaceutical preparations in medical engineering, and relates to a drug-loaded polymer microsphere, in particular to a gelatin-chitosan / montmorillonite drug-loaded microsphere and a preparation method thereof. Background technique

[0002] In recent years, the application of biodegradable polymer materials as drug carriers in medicine has attracted more and more attention, especially the drug-loaded microspheres prepared by encapsulating drugs in polymer materials. Microspheres can be specifically distributed in the body, using the targeting of designated organs and tissues and the sustained release of drugs to reduce the toxic and side effects of drugs, improve the bioavailability of drugs, reduce the number of administrations and doses, and reduce the burden on patients. Pain, minimize the toxic and side effects of drugs.

[0003] Some hydrophilic drugs, such as acyclovir, 5-fluoropyrimidine, doxorubicin, gent...

Examples

Embodiment 1

[0052] (1) Take the hydrophilic drug ofloxacin and dissolve it in 10ml mass concentration of 1% gelatin aqueous solution with a molecular weight of 100,000, the mass ratio of ofloxacin to gelatin is 0.5: 1, with 1 drop / s Add dropwise the montmorillonite suspended aqueous solution with a mass concentration of 2% after ultrasonic treatment, the mass ratio of montmorillonite to gelatin is 0.02:1, and under stirring at a constant temperature of 50°C, the intercalation reaction is carried out for 40 minutes to obtain solution A;

[0053] (2) dissolving chitosan with a molecular weight of 300,000 in 1% acetic acid aqueous solution, and stirring rapidly, until chitosan is completely dissolved, it is B that the mass concentration that is mixed with chitosan is 2%;

[0054] (3) Stir and emulsify liquid paraffin with a volume ratio of 18:1 and emulsifier Span-80 at a constant temperature of 60° C. for 30 minutes at a stirring speed of 400 rpm to obtain emulsion C;

[0055] (4) Add 10ml ...

Embodiment 2

[0060] (1) Take the hydrophilic drug ofloxacin and dissolve it in the gelatin aqueous solution of 100,000 with the molecular weight of 2% in 10ml mass concentration, the mass ratio of ofloxacin and gelatin is 0.15: 1, with 2 drops / s 1.5% montmorillonite suspension aqueous solution was added dropwise at a speed of 1.5% after ultrasonic treatment, the mass ratio of montmorillonite to gelatin was 0.2:1, and under constant temperature stirring at 60°C, the intercalation reaction was carried out for 80 minutes to obtain solution A;

[0061] (2) dissolving chitosan with a molecular weight of 300,000 in 2% acetic acid aqueous solution, and stirring rapidly, until chitosan is completely dissolved, it is B that the mass concentration that is mixed with chitosan is 2%;

[0062] (3) Stir and emulsify liquid paraffin with a volume ratio of 19:1 and emulsifier Span-80 at a constant temperature of 70° C. for 40 minutes at a stirring speed of 400 rpm to obtain emulsion C;

[0063] (4) Add 10...

Embodiment 3

[0068] (1) Take the hydrophilic drug ofloxacin and dissolve it in the gelatin aqueous solution of 100,000 in the molecular weight of 5% in 10ml mass concentration, the mass ratio of ofloxacin and gelatin is 0.75: 1, with 2 drops / s 1% montmorillonite suspension aqueous solution was added dropwise at a speed of 1% after ultrasonic treatment, the mass ratio of montmorillonite to gelatin was 0.3:1, and under stirring at a constant temperature of 70°C, the intercalation reaction was carried out for 90 minutes to obtain solution A;

[0069] (2) molecular weight is 300,000 chitosan dissolved in 3% acetic acid aqueous solution, and stir rapidly, until chitosan dissolves completely, the mass concentration that is mixed with chitosan is 2% solution is B;

[0070] (3) Stirring and emulsifying liquid paraffin with a volume ratio of 20:1 and emulsifier Span-80 at a constant temperature of 80° C. for 50 minutes at a stirring speed of 400 rpm to obtain emulsion C;

[0071] (4) Add 10ml of so...

technical field

[0001] The invention belongs to the field of pharmaceutical preparations in medical engineering, and relates to a drug-loaded polymer microsphere, in particular to a gelatin-chitosan / montmorillonite drug-loaded microsphere and a preparation method thereof. Background technique

[0002] In recent years, the application of biodegradable polymer materials as drug carriers in medicine has attracted more and more attention, especially the drug-loaded microspheres prepared by encapsulating drugs in polymer materials. Microspheres can be specifically distributed in the body, using the targeting of designated organs and tissues and the sustained release of drugs to reduce the toxic and side effects of drugs, improve the bioavailability of drugs, reduce the number of administrations and doses, and reduce the burden on patients. Pain, minimize the toxic and side effects of drugs.

[0003] Some hydrophilic drugs, such as acyclovir, 5-fluoropyrimidine, doxorubicin, gent...

Examples

Embodiment 1

[0052] (1) Take the hydrophilic drug ofloxacin and dissolve it in 10ml mass concentration of 1% gelatin aqueous solution with a molecular weight of 100,000, the mass ratio of ofloxacin to gelatin is 0.5: 1, with 1 drop / s Add dropwise the montmorillonite suspended aqueous solution with a mass concentration of 2% after ultrasonic treatment, the mass ratio of montmorillonite to gelatin is 0.02:1, and under stirring at a constant temperature of 50°C, the intercalation reaction is carried out for 40 minutes to obtain solution A;

[0053] (2) dissolving chitosan with a molecular weight of 300,000 in 1% acetic acid aqueous solution, and stirring rapidly, until chitosan is completely dissolved, it is B that the mass concentration that is mixed with chitosan is 2%;

[0054] (3) Stir and emulsify liquid paraffin with a volume ratio of 18:1 and emulsifier Span-80 at a constant temperature of 60° C. for 30 minutes at a stirring speed of 400 rpm to obtain emulsion C;

[0055] (4) Add 10ml ...

Embodiment 2

[0060] (1) Take the hydrophilic drug ofloxacin and dissolve it in the gelatin aqueous solution of 100,000 with the molecular weight of 2% in 10ml mass concentration, the mass ratio of ofloxacin and gelatin is 0.15: 1, with 2 drops / s 1.5% montmorillonite suspension aqueous solution was added dropwise at a speed of 1.5% after ultrasonic treatment, the mass ratio of montmorillonite to gelatin was 0.2:1, and under constant temperature stirring at 60°C, the intercalation reaction was carried out for 80 minutes to obtain solution A;

[0061] (2) dissolving chitosan with a molecular weight of 300,000 in 2% acetic acid aqueous solution, and stirring rapidly, until chitosan is completely dissolved, it is B that the mass concentration that is mixed with chitosan is 2%;

[0062] (3) Stir and emulsify liquid paraffin with a volume ratio of 19:1 and emulsifier Span-80 at a constant temperature of 70° C. for 40 minutes at a stirring speed of 400 rpm to obtain emulsion C;

[0063] (4) Add 10...

Embodiment 3

[0068] (1) Take the hydrophilic drug ofloxacin and dissolve it in the gelatin aqueous solution of 100,000 in the molecular weight of 5% in 10ml mass concentration, the mass ratio of ofloxacin and gelatin is 0.75: 1, with 2 drops / s 1% montmorillonite suspension aqueous solution was added dropwise at a speed of 1% after ultrasonic treatment, the mass ratio of montmorillonite to gelatin was 0.3:1, and under stirring at a constant temperature of 70°C, the intercalation reaction was carried out for 90 minutes to obtain solution A;

[0069] (2) molecular weight is 300,000 chitosan dissolved in 3% acetic acid aqueous solution, and stir rapidly, until chitosan dissolves completely, the mass concentration that is mixed with chitosan is 2% solution is B;

[0070] (3) Stirring and emulsifying liquid paraffin with a volume ratio of 20:1 and emulsifier Span-80 at a constant temperature of 80° C. for 50 minutes at a stirring speed of 400 rpm to obtain emulsion C;

[0071] (4) Add 10ml of so...

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