Preparation method and application of a pH-responsive calcium alginate/vaterite calcium carbonate composite microsphere with controllable release rate

A technology of release rate and composite microspheres, which is applied in the direction of medical preparations of non-active ingredients, pharmaceutical formulas, inorganic non-active ingredients, etc., can solve the problems of poor mechanical strength, weak drug loading capacity, water absorption and easy breakage, etc., and achieve the goal of overcoming Unstable crystal form, reducing the effect of initial burst release

Active Publication Date: 2020-04-21
SUN YAT SEN UNIV
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  • Abstract
  • Description
  • Claims
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Problems solved by technology

[0005] The present invention aims at the problems of single calcium alginate hydrogel with large network void size, poor mechanical strength, easy to break when absorbing water, unstable crystal form of vaterite calcium carbonate, and weak drug loading capacity. Calcium carbonate and calcium alginate are combined to obtain calcium alginate hydrogel composite microspheres embedded with vaterite calcium carbonate inside, providing a pH-responsive calcium alginate / vaterite calcium carbonate composite microsphere with controllable release rate

Method used

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  • Preparation method and application of a pH-responsive calcium alginate/vaterite calcium carbonate composite microsphere with controllable release rate
  • Preparation method and application of a pH-responsive calcium alginate/vaterite calcium carbonate composite microsphere with controllable release rate
  • Preparation method and application of a pH-responsive calcium alginate/vaterite calcium carbonate composite microsphere with controllable release rate

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Embodiment 1

[0038] A pH-responsive calcium alginate / vaterite calcium carbonate composite microsphere with controllable release rate is prepared by the following method:

[0039] (1) Co-precipitation method to prepare vaterite calcium carbonate suspension: add Na at a concentration of 50mM to a beaker with a capacity of 100mL 2 CO 3+8mg / mL casein 20mL, 600rpm magnetic stirring, magnet diameter 40mm, at the same time add 20mL50mM CaCl in the separatory funnel 2 , Open the cock just above the beaker and add evenly. Stir magnetically for 20 minutes. After the stirring is completed, the carbonate ions and calcium ions in the solution react completely at this time to obtain CaCO 3 Suspension, i.e. vaterite calcium carbonate suspension, in which CaCO 3 The concentration is 2.5mg / mL.

[0040] (2) Prepare a sodium alginate (SA) solution with a mass concentration of 2%: weigh the SA powder, add water and stir to prepare an SA solution with a mass concentration of 2%.

[0041] (3) Prepare the i...

Embodiment 2

[0046] The effect of the type of external phase and the flow rate on the composite microspheres was investigated.

[0047] The external phase is set to dichloromethane, dichloromethane+surfactant, ethyl acetate+surfactant, wherein there are many choices of surfactants, taking the commonly used Span80 as an example, the mass ratio of its addition is 3% of the external phase %. The flow rates of the external phase were set to 50 μL / min, 200 μL / min, 400 μL / min, and 800 μL / min, respectively.

[0048] (1) Taking single calcium alginate as a comparative example, according to the above-mentioned different types of external phases and flow rates, the influence of the type of external phase on single calcium alginate microspheres was investigated.

[0049] The result is as image 3 As shown, the external phase of Figure A is dichloromethane, and the single calcium alginate microspheres and composite microspheres are elliptical; the external phase of Figure a is dichloromethane+3% Spa...

Embodiment 3

[0052] The effect of the added amount of vaterite calcium carbonate on the shape and particle size of composite microspheres was investigated.

[0053] When preparing composite microspheres according to the method in Example 1, during the preparation of the internal phase, the volumes of the vaterite calcium carbonate suspension drawn were respectively 2 mL, 8 mL and 16 mL, i.e. the vaterite in the internal phase The quality of calcium carbonate is 5mg, 20mg and 40mg respectively, according to the quality of vaterite calcium carbonate, it is divided into A-5 group, A-20 group and A-40 group respectively. Observe the shape and particle size of the composite microspheres prepared by A-5 group, A-20 group and A-40 group, the results are as follows: Figure 5 shown. Figures a, b and c correspond to group A-5, group A-20 and group A-40, respectively. The results show that after adding different amounts of vaterite calcium carbonate, the prepared composite microspheres have no cha...

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Abstract

The invention provides a calcium alginate / vaterite calcium carbonate composite microsphere with a controllable pH-responsive type releasing rate as well as a preparation method and application thereof. The composite microsphere is prepared by uniformly mixing a uniformly-dispersed vaterite calcium carbonate suspension and a sodium alginate solution, and preparing by using a micro-fluidic device; the vaterite calcium carbonate is prepared by a co-precipitation method; the particle size of the vaterite calcium carbonate is 1-4 microns. The composite microsphere is uniform in size and high in dispersibility, has good pH response characteristic and an effect of neutralizing the acidic environment; the initial explosive release of the loaded drug is effectively reduced; the releasing time can last for more than one week; the releasing rate can be controlled by the content of the vaterite calcium carbonate; meanwhile, the composite microsphere is high in safety. In addition, the preparationmethod of the calcium alginate / vaterite calcium carbonate composite microsphere with the controllable pH-responsive type releasing rate is simple and efficient; the costs of the raw materials are low;the industrial large-scale production can be facilitated.

Description

technical field [0001] The invention relates to the technical field of droplet generation and preparation of hydrogel polymer microspheres, and more specifically, to a preparation method and application of a pH-responsive calcium alginate / vaterite calcium carbonate composite microsphere with controllable release rate. Background technique [0002] The drug release involved in the field of biology is based on a certain matrix material as a carrier, embedding specific drug components, and releasing them to patients in a specific form or at a controlled rate. Among them, the material and morphology of the carrier play a crucial role in the process of drug release. Drug sustained-release system is conducive to improving the efficacy of drugs, can reduce the number of dressing changes, and is of great significance to improving the level of clinical drug use. [0003] Biodegradable hydrogels have been widely used in tissue engineering and drug delivery, and can be used as cartila...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K9/16A61K47/36A61K47/02
CPCA61K9/1611A61K9/1652
Inventor 李燕史明张伊玲刘筱芳高芸芬轩留洋
Owner SUN YAT SEN UNIV
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