CN102219938A - Preparation method of hydrophobically modified sodium alginate - Google Patents

Abstract

The invention relates to a preparation method of hydrophobically modified sodium alginate gel, which belongs to the technical field of biomedical materials. The present invention prepares a star-shaped polymer containing inorganic substances and hydrophobic polymers, and then uses ultrasonic dispersion technology to disperse the self-made polymer into sodium alginate solution through ultrasonic dispersion, and obtains it with hydrophobicity at the same time by the drop method and hydrophilic calcium alginate hybrid gel. The hydrophobic drug ibuprofen has a high embedding rate in it, reaching more than 90%, and has a good sustained release effect. The drug release is reduced by nearly 45% in the first 2 hours, overcoming the hydrophilicity of sodium alginate. Strong, the loading capacity of hydrophobic drugs is not high, and problems such as sudden release are prone to occur in the early stage of drug release. The drug-loaded microsphere of the invention is easy to prepare, has controllable particle diameter (about 1 mm), good biocompatibility, is completely nontoxic to human body, and has potential application value as a drug carrier.

Description

A kind of preparation method of hydrophobically modified sodium alginate

technical field

The invention relates to a preparation method of hydrophobically modified sodium alginate gel, which belongs to the technical field of biomedical materials.

Background technique

Sodium alginate is a high-molecular compound extracted from brown algae. It has rich sources of raw materials, good biocompatibility, no immunogenicity to biological tissues, biodegradability, and non-toxic degradation products; compared with other polymers, Low price, rich sources, better hydrophilicity, easy cell adsorption, easy penetration of nutrients, etc.; compared with other natural polymers, it can form a variety of performance requirements with divalent calcium cations under mild conditions. Gel, so it has a wide range of applications in the food industry, cosmetic industry and pharmaceutical industry. Among them, in the pharmaceutical industry, sodium alginate has been widely used as a drug carrier for many years to prepare various drug delivery systems such as pills, powders, and tablets. However, in terms of embedding hydrophobic drugs, the above-mentioned dosage forms have great defects in terms of sustained release effect, embedding rate, and increase in drug stability, resulting in a low overall bioavailability.

However, many excellent hydrophobic drugs such as ibuprofen, doxorubicin, itraconazole, etc. are quite good drugs in the treatment of diseases, but they have low solubility in sodium alginate gel and low availability , the application is limited. In order to improve the availability, people have adopted a variety of research methods, such as: increasing the total specific surface area by grinding to increase solubility, particle crystallization, spray drying, etc., but these methods have their own shortcomings, such as poor dispersion and poor stability. , the particle size distribution is too wide, etc.

Contents of the invention

The object of the present invention is to provide a method for preparing hydrophobically modified sodium alginate gel. The substance involved in the present invention is based on polyhydroxyl cage octapolysilsesquioxane (abbreviated as POSS-(OH) ₃₂ ) 1. Polylactic acid is a star-shaped polymer chain, which is ultrasonically dispersed into sodium alginate, and the calcium alginate gel is made into calcium alginate gel by the droplet method, which can effectively increase the drug load and make it have a good sustained-release effect.

The present invention makes full use of the inherent non-toxicity, good water solubility, and good biocompatibility of the natural biological polysaccharide-sodium alginate, etc., carries out hydrophobic modification and makes microspheres, that is, synthesizes a new type of biodegradable Sexual materials as drug carriers.

The laboratory-made star polymer (Figure 1) is an inorganic-organic hybrid material. It has a Si-O-Si cage hexahedral structure as the core and polylactic acid as the side chain. It can be used as a storage warehouse for hydrophobic drugs and is biocompatible. The sex is very good. The final products of polylactic acid metabolism in the body are CO ₂ and H ₂ O. The intermediate product lactic acid is also a normal metabolite in the body, so it does not accumulate in vital organs. In addition, the strong interaction with hydrophobic drugs can greatly increase the loading capacity of hydrophobic drugs, and at the same time slow down the release rate of drugs.

The preparation method of hydrophobically modified sodium alginate microspheres: Dissolve the self-made star-shaped polymer in the laboratory in the dimethyl sulfoxide solution, add it into the sodium alginate solution under high-speed stirring, and disperse it with an ultrasonic instrument after 20 minutes 2 minutes; absorb the solution with a syringe, drop the solution into a 3% CaCl ₂ solution by the drop method, ripen, wash with water, and dry to obtain the prepared microspheres.

Advantages of the present invention:

1. The raw material of the present invention is natural sodium alginate, which has good biocompatibility, degradability and low price. The synthetic star-shaped polymer uses POSS as the core and polylactic acid as the chain, which is non-toxic, non-irritating, and has good biocompatibility and good degradability.

2. The hydrogel prepared by the droplet method is simple and easy to operate, and the shapes are all round and regular, and the size is consistent.

3. It can increase the embedding rate of hydrophobic drugs in sodium alginate and delay the release rate, so it can be used as a drug carrier for the embedding and release of various drugs, especially hydrophobic drugs.

Description of drawings

Figure 1a POSS-PLA, POSS is a star-shaped polymer with core polylactic acid as the chain, cage-type siloxane as the core, and polylactic acid as the chain star polymer; b Hydrophobically modified sodium alginate gel pellet structure Schematic diagram, red represents POSS-PLA.

Fig. 2 is the drug release curve of the hydrophobically modified microspheres prepared in Examples 1, 2, and 3.

Fig. 3 is the drug release curve of the hydrophobically modified microspheres prepared in Examples 1, 4, and 5.

Detailed ways

Example 1

Take a certain amount of ibuprofen and 100 mg POSS-PLA (Mn=6.22×10 ⁴ ) dissolved in dimethyl sulfoxide, drop into 50 mL of 2% sodium alginate aqueous solution under high-speed stirring, and continue stirring for 20 Minutes, then use a self-made ultrasonic device to sonicate for 2 minutes, take the mixed solution, drop it into a 3% CaCl ₂ solution with a 6# medical needle, mature for 2 hours, wash the gel with distilled water for 3 times, filter and separate, The hydrophobically modified sodium alginate microspheres are obtained after drying.

Example 2

The relative molecular mass of the star polymer POSS-PLA was added to be 2.51×10 ⁴ , and the other steps were the same as in Example 1.

Example 3

The relative molecular mass of the star polymer POSS-PLA was added to be 14.85×10 ⁴ , and the other steps were the same as in Example 1.

Example 4

The mass ratio of sodium alginate and POSS-PLA is 100:5, and other steps are the same as in Example 1.

Example 5

The mass ratio of sodium alginate and POSS-PLA is 100:15, and other steps are the same as in Example 1.

Example 6

Release curves of sodium alginate microspheres with different contents of star-shaped polylactic acid: Weigh a certain mass of microsphere samples prepared in Example 1, Example 2, and Example 3, and measure drug release at 37°C and 200mL pH 7.2 phosphate buffer Velocity, plot the release curve.

The embedding rate of the drug-loaded microspheres prepared by the above method reached more than 90%, and increased with the increase of the star-shaped polylactic acid, while the drug release rate decreased with the increase of the star-shaped polylactic acid content (Figure 2), because the star-shaped polylactic acid The polymer with cage-type siloxane as the core and hydrophobic polylactic acid as the chain can be used as a drug storage warehouse, and the interaction with the hydrophobic drug is strengthened, so that the dissolution rate of the drug from the sodium alginate microspheres is reduced. It can be seen from the figure that the drug-loaded microspheres have a good sustained-release effect, and the sustained-release rate can be controlled by adjusting the mass ratio of the star polymer to sodium alginate.

Example 7

Release curves of sodium alginate microspheres containing star-shaped polymers of different molecular weights: Weigh a certain mass of microsphere samples prepared in Example 1, Example 4, and Example 5, and measure Drug release rate, draw the release curve.

It can be seen from Figure 3 that when the mass ratio of star-shaped polylactic acid to sodium alginate remains unchanged, as the molecular weight of the star-shaped polymer increases, the drug release rate decreases, and the growth of the polylactic acid arm is closely related to the hydrophobic drug. The interaction increases, thereby reducing the dissolution rate of the drug. Therefore, the sustained release rate of the drug-loaded microspheres can be adjusted by the relative molecular mass of the star polymer.

Claims (5)

1. A hydrophobically modified sodium alginate hydrogel, which is a composite of a star-shaped polymer and sodium alginate, is characterized in that the laboratory-made star-shaped polymer (Figure 1a) is ultrasonically dispersed into alginic acid Sodium solution, using the drop method to drop into calcium chloride aqueous solution to form a gel gel, that is, to prepare a hydrophobic modified sodium alginate gel (Figure 1b). 2. star polylactic acid according to claim 1, it is characterized in that be that nucleus is with polyhydroxyl cage octapolysilsesquioxane (POSS-(OH) ₃₂ ), carry out activity with D, L-lactide The star polymer POSS-PLA was obtained by ring-opening polymerization. 3. The mass ratio of the star-shaped polymer according to claim 1 to sodium alginate is 5:100 to 15:100. 4. The preparation method of hydrophobically modified sodium alginate hydrogel, take a certain amount of POSS-PLA and dissolve it in dimethyl sulfoxide, drop it into an aqueous solution of sodium alginate with a mass fraction of 2% under high-speed stirring, and continue stirring for 20 Minutes, then use a self-made ultrasonic device to sonicate for 2 minutes, take the mixed solution, drop it into a 3% _CaCl solution with a 6# medical needle, mature for 2 hours, rinse the gel with distilled water for 3 times, filter, and dry at low temperature That is, hydrophobically modified sodium alginate microspheres were prepared. 5. according to claim 4, the volume ratio of solvent dimethyl sulfoxide consumption and sodium alginate solution is 4%～6%.

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