Diacerein injection type thermo-sensitive gel and method for preparing same

Abstract

The invention provides diacerein injection type thermo-sensitive gel. The diacerein injection type thermo-sensitive gel comprises diacerein, poloxamer 407, poloxamer 188 and HPMC (hydroxypropyl methylcelluloses). A concentration ratio (w / v) of the diacerein to the P-407 to the P-188 to the HPMC is 0.5%:17-22%:1-5%:0.3-1.0%. A method for preparing the diacerein injection type thermo-sensitive gelincludes preparation steps of swelling the HPMC by the aid of water at the room temperature to obtain HPMC solution; uniformly scattering the poloxamer P-407 and the poloxamer P-188 on the surface ofthe HPMC solution and carrying out overnight swelling and dissolving to obtain blank thermo-sensitive gel solution; sufficiently dissolving the diacerein by the aid of DMSO (dimethyl sulfoxide) to obtain diacerein solution and then adding the diacerein solution into the blank thermo-sensitive gel solution to obtain diacerein thermo-sensitive gel solution. The diacerein injection type thermo-sensitive gel and the method have the advantages that the diacerein injection type thermo-sensitive gel prepared by the aid of the method is prepared from water-soluble high-polymer materials, is excellentin histocompatibility and bio-adhesion, is long in detention time at medication positions, can be slowly released and is long-acting, and the purpose of reducing side effects on gastrointestinal tracts can be achieved.

Description

technical field

[0001] The invention belongs to the technical field of pharmaceutical preparations, and in particular relates to a diacerein injection-type temperature-sensitive gel and a preparation method thereof. Background technique

[0002] Osteoarthritis (OA) is a degenerative bone joint disease characterized by degeneration and destruction of articular cartilage and bone hyperplasia. The disease occurs frequently after middle age. Preliminary surveys in China show that the overall prevalence of osteoarthritis is 15%, the prevalence of people aged 40 is 10% to 17%, and that of people over 60 is 50%. And among people over the age of 75, 80% have osteoarthritis. Clinically, joint swelling and pain, bone hyperplasia and limited mobility are the most common. 80% of patients with osteoarthritis have limited activities, and 25% of patients with osteoarthritis cannot complete the main daily activities independently, which brings a heavy burden to the family and society. ...

Examples

Embodiment 1

[0036] The preparation of embodiment 1 thermosensitive gel solution

[0037] The drug-containing thermosensitive gel solution and the blank thermosensitive gel solution were prepared by cold melting method.

[0038] Preparation of blank gel solution: Swell an appropriate amount of HPMC with deionized water to form a solution, sprinkle precisely weighed poloxamer evenly on the surface of the mixture, and then refrigerate at 4°C overnight to make it slowly and fully swell And after dissolving, a clear, lump-free, uniformly dispersed blank thermosensitive gel solution was obtained for future use.

[0039] Preparation of the drug-containing gel solution: Diacerein powder plus a small amount of DMSO is fully mixed and uniform, and the solution is left to stand until the solution is clarified, and then added to a blank gel solution to prepare a drug-containing thermosensitive gel solution.

Embodiment 2

[0040] The investigation of embodiment 2 thermosensitive gelling temperature

[0041] The temperature-sensitive gelling temperature was measured by the test tube inversion method.

[0042] Put 2mL of temperature-sensitive gel solution into a graduated test tube, and insert a precision thermometer with an accuracy of 0.1°C into a constant temperature water bath to keep the test tube water bath environment stable, and the gel heated evenly to ensure accurate measurement results. The mercury bulb of the thermometer is completely submerged below the water surface. Set the initial temperature of the water bath to 25°C, take out the test tube and turn it over every time the temperature rises by 0.5°C, and observe the gelation situation, until the gel solution solidifies, read the scale value of the thermometer immediately, this temperature is the gelation temperature, each sample Parallel measurement was performed 3 times, and the results were averaged. Compared with the magnetic ...

Embodiment 3

[0043] Embodiment 3 thermosensitive gel prescription screening

[0044] Effects of P-407 and P188 on Gel Temperature

[0045] P407 and P188 were prepared in different concentration ratios according to the cold melting method of Example 1 to prepare a temperature-sensitive gel solution, and the temperature-sensitive gelling temperature was measured by the test tube inversion method in Example 2. The specific results are shown in Table 1.

[0046] Table 1 Effect of different concentration ratios of P407 and P188 on gelation temperature

[0047]

[0048]

[0049] It can be seen from Table 1 that the different concentration ratios of P407 and P188 have a great influence on the temperature-sensitive gel phase transition temperature. Within a certain range, the temperature-sensitive gel temperature decreases with the increase of the concentration of P407, and increases with the increase of the concentration of P188. . It can be seen from Table 1 that the gelling temperature...

technical field

[0001] The invention belongs to the technical field of pharmaceutical preparations, and in particular relates to a diacerein injection-type temperature-sensitive gel and a preparation method thereof. Background technique

[0002] Osteoarthritis (OA) is a degenerative bone joint disease characterized by degeneration and destruction of articular cartilage and bone hyperplasia. The disease occurs frequently after middle age. Preliminary surveys in China show that the overall prevalence of osteoarthritis is 15%, the prevalence of people aged 40 is 10% to 17%, and that of people over 60 is 50%. And among people over the age of 75, 80% have osteoarthritis. Clinically, joint swelling and pain, bone hyperplasia and limited mobility are the most common. 80% of patients with osteoarthritis have limited activities, and 25% of patients with osteoarthritis cannot complete the main daily activities independently, which brings a heavy burden to the family and society. ...

Examples

Embodiment 1

[0036] The preparation of embodiment 1 thermosensitive gel solution

[0037] The drug-containing thermosensitive gel solution and the blank thermosensitive gel solution were prepared by cold melting method.

[0038] Preparation of blank gel solution: Swell an appropriate amount of HPMC with deionized water to form a solution, sprinkle precisely weighed poloxamer evenly on the surface of the mixture, and then refrigerate at 4°C overnight to make it slowly and fully swell And after dissolving, a clear, lump-free, uniformly dispersed blank thermosensitive gel solution was obtained for future use.

[0039] Preparation of the drug-containing gel solution: Diacerein powder plus a small amount of DMSO is fully mixed and uniform, and the solution is left to stand until the solution is clarified, and then added to a blank gel solution to prepare a drug-containing thermosensitive gel solution.

Embodiment 2

[0040] The investigation of embodiment 2 thermosensitive gelling temperature

[0041] The temperature-sensitive gelling temperature was measured by the test tube inversion method.

[0042] Put 2mL of temperature-sensitive gel solution into a graduated test tube, and insert a precision thermometer with an accuracy of 0.1°C into a constant temperature water bath to keep the test tube water bath environment stable, and the gel heated evenly to ensure accurate measurement results. The mercury bulb of the thermometer is completely submerged below the water surface. Set the initial temperature of the water bath to 25°C, take out the test tube and turn it over every time the temperature rises by 0.5°C, and observe the gelation situation, until the gel solution solidifies, read the scale value of the thermometer immediately, this temperature is the gelation temperature, each sample Parallel measurement was performed 3 times, and the results were averaged. Compared with the magnetic ...

Embodiment 3

[0043] Embodiment 3 thermosensitive gel prescription screening

[0044] Effects of P-407 and P188 on Gel Temperature

[0045] P407 and P188 were prepared in different concentration ratios according to the cold melting method of Example 1 to prepare a temperature-sensitive gel solution, and the temperature-sensitive gelling temperature was measured by the test tube inversion method in Example 2. The specific results are shown in Table 1.

[0046] Table 1 Effect of different concentration ratios of P407 and P188 on gelation temperature

[0047]

[0048]

[0049] It can be seen from Table 1 that the different concentration ratios of P407 and P188 have a great influence on the temperature-sensitive gel phase transition temperature. Within a certain range, the temperature-sensitive gel temperature decreases with the increase of the concentration of P407, and increases with the increase of the concentration of P188. . It can be seen from Table 1 that the gelling temperature...

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