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Preparation method of hollow microspheres and application thereof

A hollow and composite microsphere technology, applied in the fields of polymer materials and biomedical engineering, can solve the problems of uneven structure of microspheres, long degradation time, high density of microspheres, etc., and achieve easy industrial production, simple preparation process, avoidance of high density effect

Pending Publication Date: 2020-11-03
JIANGSU PURECELL BIOMEDICAL TECH CO LTD
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Problems solved by technology

[0007] In order to solve the problem that the oil-water two phases are easy to separate during the emulsification process of preparing microspheres, and the internal structure of the microspheres is not uniform, which leads to the problems of high microsphere density and long degradation time, the present invention uses PLGA as a raw material, and first dissolves PLGA in an organic solvent After mixing with alcohol, the PLGA microspheres with a hollow interior and a diameter of 100-500 μm are prepared by the emulsification method

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  • Preparation method of hollow microspheres and application thereof
  • Preparation method of hollow microspheres and application thereof
  • Preparation method of hollow microspheres and application thereof

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preparation example Construction

[0064] The invention provides a method for preparing hollow PLGA microspheres. The method includes the following steps:

[0065] 1) PLGA is dissolved in an organic solvent to obtain a PLGA solution;

[0066] 2) adding the porogen to the PLGA solution in step 1), and homogenizing to form a mixed solution;

[0067] 3) adding the mixed solution in step 2) into the PVA aqueous solution below the liquid level, and stirring to form an emulsion, and after removing the porogen and the organic solvent, a residue is obtained;

[0068] 4) collecting and washing the residue in step 3) to obtain hollow PLGA microspheres with a diameter of 100-500 μm;

[0069] 5) surface activation of the hollow PLGA microspheres in step 4) to obtain activated hollow PLGA microspheres;

[0070] 6) Mix and react the activated hollow PLGA microspheres in step 5) with the gelatin solution, collect, wash and dry to obtain hollow PLGA-gelatin composite microspheres.

[0071] In some embodiments of the presen...

Embodiment 1

[0133] Example 1: Preparation of hollow PLGA microspheres.

[0134] Weigh PLGA (50:50, Mw=30000-50000Da, carboxyl-terminated) (1 g) and dissolve it in dichloromethane (20 mL). Add absolute ethanol (10 mL), and homogenize for 60 seconds with a homogenizer at a speed of 13000 rpm. With the syringe pump that has 25G, the injection needle of inner diameter 0.25mm, mixed solution is injected in the PVA aqueous solution (2L) that mass concentration is 0.5% with the speed of 10mL / min, and mechanical stirring speed is 200rpm, stirs 12h, volatilizes to remove two Chloromethane. Washed 3 times with double distilled water, collected by centrifugation, obtained as Figures 1A-1B The hollow PLGA microspheres shown.

[0135] The resulting hollow PLGA microspheres have a diameter of 100 μm and a density of 1.00-1.10 g / cm 3 .

Embodiment 2

[0136] Example 2: Preparation of hollow PLGA microspheres.

[0137] Weigh PLGA (75:25, Mw=66000~105000Da, ester-terminated) (1g), dissolve in dichloromethane (20mL), add absolute ethanol (10mL), homogenize for 60s with a homogenizer, and homogenize The speed is 13000rpm. With the syringe pump that has 25G, the injection needle of inner diameter 0.25mm, mixed solution is injected in the PVA aqueous solution (2L) that mass concentration is 0.5% with the speed of 10mL / min, and mechanical stirring speed is 200rpm, stirs 12h, volatilizes to remove two Chloromethane. Washed 3 times with double distilled water, collected by centrifugation, obtained as figure 2 The hollow PLGA microspheres shown.

[0138] Depend on Figure 3A-3B It can be seen that the diameter of the hollow PLGA microspheres prepared by the above method is about 150 μm, the size distribution is uniform, the surface is relatively smooth (under a magnified view of 1.50kX), the outer wall is thinner, and the interi...

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Abstract

The invention belongs to the technical field of high polymer materials and biomedical engineering, and relates to a preparation method of hollow microspheres and application thereof. Alcohol (especially ethanol) which is mutually soluble with an organic solvent and water is used as a pore-foaming agent, and the polylactic acid glycolic acid microspheres are prepared through a one-step emulsification method. The microsphere prepared by the method has the characteristics of hollow interior, small density, diameter of 100-500 microns and narrow diameter distribution; microspheres with different internal structures can be prepared by adjusting the use amount of alcohol, and after the surfaces of the microspheres are modified with materials (such as gelatin) with biological activity, the microspheres have high application value in tissue engineering and cell carriers. Alcohol serving as a pore-foaming agent can form a stable solution with an oil phase, layering is avoided, and uniform microspheres with hollow interiors are obtained; meanwhile, the obtained microspheres are small in density, the diameter ranges from 100-500 microns , the requirements of three-dimensional cell culture microcarriers are met, and the method is suitable for cell culture.

Description

technical field [0001] The invention belongs to the technical field of polymer materials and biomedical engineering, and relates to a method for preparing hollow microspheres, hollow microspheres prepared by the method, and applications of the hollow microspheres. Background technique [0002] Poly(lactic-co-glycolic acid), PLGA is a random copolymer of two monomers - lactic acid (LA) and glycolic acid (GA), biodegradable, Safe and non-toxic polymer materials, decomposed into CO after degradation in the body 2 and H 2 O. PLGA has good biocompatibility, and was approved by the US FDA as a pharmaceutical excipient in 1997, and has a wide range of applications in the field of tissue engineering. [0003] Since the degradation time of solid PLGA microspheres is very long in vivo and in vitro, its application range is limited. Therefore, the preparation of porous microspheres and the acceleration of microsphere degradation have become a research hotspot in recent years. There...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C08J3/16C08J3/12C08J7/12C08J9/28C08J9/36C08L67/04C12N5/00
CPCC08J3/16C08J3/12C08J7/12C08J9/28C08J9/36C12N5/0075C12N5/0062C08J2367/04C12N2513/00C12N2531/00C12N2533/40C12N2533/54
Inventor 孙振华黄珂李英文施坤宁杨慧莹蒋雪峰
Owner JIANGSU PURECELL BIOMEDICAL TECH CO LTD
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