A kind of injectable polyhydroxyalkanoate microsphere and preparation method thereof

Abstract

The invention relates to the technical field of biomedicine, and specifically discloses an injectable polyhydroxyalkanoate (PHA) microsphere and a preparation method thereof. The preparation method of the injectable polyhydroxyalkanoate microspheres comprises: a) dissolving the PHA material in an organic solvent to obtain an oil phase; b) dissolving hyaluronic acid in water to obtain an aqueous phase; c) under stirring conditions Next, add the oil phase to the water phase dropwise, after the dropwise addition, continue to stir to volatilize the organic solvent, and then perform solid-liquid separation and drying to obtain PHA microspheres; the steps a) and b) ) has no order restriction. The above method of the present invention can improve the dispersibility of the PHA microspheres, and the obtained microspheres can be quickly dispersed in water, the microspheres are complete in shape, independent of each other, and have no agglomeration phenomenon, thereby avoiding clogging of the needle and facilitating subsequent injection as a filler. Moreover, PHA microspheres have excellent biocompatibility and will not cause rejection, and can achieve long-term filling effects.

Description

technical field

[0001] The invention relates to the technical field of biomedicine, in particular to an injectable polyhydroxyalkanoate microsphere and a preparation method thereof. Background technique

[0002] As humans age or are affected by certain diseases, the muscle and collagen tissue in the human body will have different degrees of functional degeneration, causing skin depressions, gastric reflux and other problems. Therefore, people have invented a variety of fillers to improve Fill in sunken skin or stimulate muscle and collagen regrowth through foreign substances, such as hyaluronic acid, bovine collagen, etc. However, the filling effect of these substances as fillers lasts for a short period of time, and frequent injections are required to maintain the filling effect. In order to achieve a long-term filling effect, people have tried to use biodegradable materials to make microspheres as fillers, such as polyvinyl alcohol (PVA), polymethyl methacrylate (PMMA) an...

Examples

preparation example Construction

[0038] The invention provides a preparation method of injectable polyhydroxyalkanoate microspheres, comprising the following steps:

[0039] a) dissolving the PHA material in an organic solvent to obtain an oil phase;

[0040] b) dissolving hyaluronic acid in water to obtain an aqueous phase;

[0041] c) adding the oil phase to the water phase dropwise under stirring conditions, after the dropwise addition, continue stirring to volatilize the organic solvent, and then perform solid-liquid separation and drying to obtain PHA microspheres;

[0042] The steps a) and b) are not limited in order.

[0043]In the preparation method provided by the present invention, the PHA material is dissolved in an organic solvent to obtain an oil phase, the hyaluronic acid aqueous solution is used as the water phase, the water phase solution is stirred, and the oil phase is slowly added to the water phase, and the organic solvent is continuously stirred. Volatilization, followed by solid-liquid...

Embodiment 1

[0068]Dissolve 1 g of PHBHHx (molecular weight 20-100 KDa, average molecular weight 50 KDa) in 20 mL of dichloromethane to make an organic solution with a final concentration of 5% (w / v), which is the oil phase. Dissolve hyaluronic acid (molecular weight 5-100 KDa, average molecular weight 50KDa) in distilled water to prepare an aqueous solution with a final concentration of 0.5% (w / v), which is the aqueous phase. A magnetic stirrer was used to stir the water phase at a speed of 400 rpm, and at the same time, the oil phase was slowly added dropwise to the water phase under stirring, and the volume ratio of the two solutions was 1:50. Continue stirring at a speed of 400 rpm with a magnetic stirrer to form an emulsion; continue stirring at this speed for 5 h to remove the organic solvent. Afterwards, the resulting solution was first frozen (-80°C for 6 h), and then freeze-dried (-40°C for 24 h) to remove water to obtain injectable PHBHHx microspheres.

[0069] According to the ...

Embodiment 2

[0071] Dissolve 1 g of PHBVHHx (molecular weight 20-100 KDa, average molecular weight 50 KDa) in 20 mL of dichloromethane to make an organic solution with a final concentration of 5% (w / v), which is the oil phase. Dissolve hyaluronic acid (molecular weight 10-200 KDa, average molecular weight 50KDa) in distilled water to prepare an aqueous solution with a final concentration of 0.5% (w / v), which is the aqueous phase. A magnetic stirrer was used to stir the water phase at a speed of 400 rpm, and at the same time, the oil phase was slowly added dropwise to the water phase under stirring, and the volume ratio of the two solutions was 1:50. Continue stirring at a speed of 400 rpm with a magnetic stirrer to form an emulsion; continue stirring at this speed for 4 h to remove the organic solvent. Afterwards, the resulting solution was first frozen (-40°C for 12 h), and then freeze-dried (-40°C for 24 h) to remove water to obtain injectable PHBVHHx microspheres.

[0072] The yield of...

technical field

[0001] The invention relates to the technical field of biomedicine, in particular to an injectable polyhydroxyalkanoate microsphere and a preparation method thereof. Background technique

[0002] As humans age or are affected by certain diseases, the muscle and collagen tissue in the human body will have different degrees of functional degeneration, causing skin depressions, gastric reflux and other problems. Therefore, people have invented a variety of fillers to improve Fill in sunken skin or stimulate muscle and collagen regrowth through foreign substances, such as hyaluronic acid, bovine collagen, etc. However, the filling effect of these substances as fillers lasts for a short period of time, and frequent injections are required to maintain the filling effect. In order to achieve a long-term filling effect, people have tried to use biodegradable materials to make microspheres as fillers, such as polyvinyl alcohol (PVA), polymethyl methacrylate (PMMA) an...

Examples

preparation example Construction

[0038] The invention provides a preparation method of injectable polyhydroxyalkanoate microspheres, comprising the following steps:

[0039] a) dissolving the PHA material in an organic solvent to obtain an oil phase;

[0040] b) dissolving hyaluronic acid in water to obtain an aqueous phase;

[0041] c) adding the oil phase to the water phase dropwise under stirring conditions, after the dropwise addition, continue stirring to volatilize the organic solvent, and then perform solid-liquid separation and drying to obtain PHA microspheres;

[0042] The steps a) and b) are not limited in order.

[0043]In the preparation method provided by the present invention, the PHA material is dissolved in an organic solvent to obtain an oil phase, the hyaluronic acid aqueous solution is used as the water phase, the water phase solution is stirred, and the oil phase is slowly added to the water phase, and the organic solvent is continuously stirred. Volatilization, followed by solid-liquid...

Embodiment 1

[0068]Dissolve 1 g of PHBHHx (molecular weight 20-100 KDa, average molecular weight 50 KDa) in 20 mL of dichloromethane to make an organic solution with a final concentration of 5% (w / v), which is the oil phase. Dissolve hyaluronic acid (molecular weight 5-100 KDa, average molecular weight 50KDa) in distilled water to prepare an aqueous solution with a final concentration of 0.5% (w / v), which is the aqueous phase. A magnetic stirrer was used to stir the water phase at a speed of 400 rpm, and at the same time, the oil phase was slowly added dropwise to the water phase under stirring, and the volume ratio of the two solutions was 1:50. Continue stirring at a speed of 400 rpm with a magnetic stirrer to form an emulsion; continue stirring at this speed for 5 h to remove the organic solvent. Afterwards, the resulting solution was first frozen (-80°C for 6 h), and then freeze-dried (-40°C for 24 h) to remove water to obtain injectable PHBHHx microspheres.

[0069] According to the ...

Embodiment 2

[0071] Dissolve 1 g of PHBVHHx (molecular weight 20-100 KDa, average molecular weight 50 KDa) in 20 mL of dichloromethane to make an organic solution with a final concentration of 5% (w / v), which is the oil phase. Dissolve hyaluronic acid (molecular weight 10-200 KDa, average molecular weight 50KDa) in distilled water to prepare an aqueous solution with a final concentration of 0.5% (w / v), which is the aqueous phase. A magnetic stirrer was used to stir the water phase at a speed of 400 rpm, and at the same time, the oil phase was slowly added dropwise to the water phase under stirring, and the volume ratio of the two solutions was 1:50. Continue stirring at a speed of 400 rpm with a magnetic stirrer to form an emulsion; continue stirring at this speed for 4 h to remove the organic solvent. Afterwards, the resulting solution was first frozen (-40°C for 12 h), and then freeze-dried (-40°C for 24 h) to remove water to obtain injectable PHBVHHx microspheres.

[0072] The yield of...

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