阅读说明：本技术 布洛芬插层蒙脱土/淀粉/纤维素复合物及其制备方法 (Ibuprofen intercalated montmorillonite/starch/cellulose compound and preparation method thereof ) 是由 杨磊 傅丽君 蔡力锋 于 2020-06-30 设计创作，主要内容包括：本发明公开了布洛芬插层蒙脱土/淀粉/纤维素复合物及其制备方法,以布洛芬、可溶性淀粉、蒙脱土、羧甲基纤维素为原料,采取溶液插层法制出了布洛芬插层蒙脱土/淀粉/纤维素复合物,用傅立叶红外光谱仪、X-射线衍射仪、扫描电镜及热重分析仪对物质结构及热稳定性进行表征；同时用紫外/可见分光光度计对复合物的药物缓释行为进行研究。结果表明：IBU已经成功负载到蒙脱土/淀粉/纤维素复合物上；该复合物稳定性较高；IBU在不同的溶液中都具有一定的缓释效果,缓释体系中IBU的释放规律表现出快速释放、慢速释放和平衡3个阶段；且IBU的释放动力学都符合准一级动力学方程。(The invention discloses an ibuprofen intercalated montmorillonite/starch/cellulose compound and a preparation method thereof, wherein ibuprofen, soluble starch, montmorillonite and carboxymethyl cellulose are used as raw materials, a solution intercalation method is adopted to prepare the ibuprofen intercalated montmorillonite/starch/cellulose compound, and a Fourier infrared spectrometer, an X-ray diffractometer, a scanning electron microscope and a thermogravimetric analyzer are used for representing the material structure and the thermal stability; meanwhile, an ultraviolet/visible spectrophotometer is used for researching the drug slow release behavior of the compound. The results show that: IBU has been successfully loaded onto montmorillonite/starch/cellulose composites; the compound has high stability; IBU has certain slow release effect in different solutions, and the release rule of IBU in a slow release system shows 3 stages of quick release, slow release and balance; and the release kinetics of IBU all accord with the quasi first order kinetic equation.)

1. The preparation method of the ibuprofen intercalated montmorillonite/starch/cellulose compound is characterized by comprising the following steps: which comprises the following steps:

1) dissolving ibuprofen in absolute ethyl alcohol, fully dissolving the ibuprofen, and adding deionized water and montmorillonite powder to prepare a suspension;

2) under the condition of stirring, adding soluble starch and carboxymethyl cellulose into the suspension, placing the suspension in a water bath kettle for heating and stirring reaction, then cooling to room temperature, centrifuging the product, collecting the solid, and drying to obtain the ibuprofen intercalated montmorillonite/starch/cellulose compound.

2. The method of claim 1, wherein the ibuprofen intercalated montmorillonite/starch/cellulose compound is prepared by the following steps: the mass ratio of the ibuprofen to the montmorillonite to the soluble starch to the carboxymethyl cellulose is 4:0.45-0.55:0.45-0.55: 0.26-0.27.

3. The method of claim 2, wherein the ibuprofen intercalated montmorillonite/starch/cellulose compound is prepared by the following steps: the mass ratio of the ibuprofen to the montmorillonite to the soluble starch to the carboxymethyl cellulose is 4:0.5:0.5: 0.267.

4. The method of claim 1, wherein the ibuprofen intercalated montmorillonite/starch/cellulose compound is prepared by the following steps: the temperature of the heating and stirring reaction in the water bath kettle is 55-65 ℃ and the time is 7.5-8.5 hours.

5. The method of claim 1, wherein the ibuprofen intercalated montmorillonite/starch/cellulose compound is prepared by the following steps: the montmorillonite is modified montmorillonite, and the preparation method comprises the following steps: mixing the montmorillonite and the hydrochloric acid solution according to the solid-liquid ratio of 1g to 50mL, heating and stirring the mixture in an oil bath kettle for reaction, cooling and layering the mixture, removing supernatant, washing a filter cake with deionized water, carrying out suction filtration to neutrality, and drying the filter cake to obtain the modified montmorillonite.

6. The method of claim 5, wherein the ibuprofen intercalated montmorillonite/starch/cellulose compound is prepared by the following steps: the mass fraction of the hydrochloric acid solution is 15%.

7. The method of claim 1, wherein the ibuprofen intercalated montmorillonite/starch/cellulose compound is prepared by the following steps: the temperature of the heating and stirring reaction in the oil bath kettle is 75-85 ℃, and the time is 7.5-8.5 hours.

8. An ibuprofen intercalated montmorillonite/starch/cellulose complex obtainable by the process according to any one of claims 1 to 7.

Technical Field

The invention relates to the technical field of slow release, in particular to a preparation method of an ibuprofen intercalated montmorillonite/starch/cellulose compound.

Background

The absorption, distribution and metabolism of drugs in humans and animals is a constantly changing process. The normal administration method does not bring better medicine curative effect, the concentration of the medicine can generate larger fluctuation in the human body, the effect is not particularly stable, sometimes the highest medicine dosage exceeding the human body or lower than the effective medicine dosage can occur, at this time, the due treatment effect is not achieved, and on the contrary, the brought disadvantage is more than the benefit. Frequent administration of small doses can theoretically achieve the desired drug concentration, and it is true that humans are unable to accept such frequent administration. The slow release effect can be better exerted by searching a proper drug carrier, so that the dosage of the drug which achieves the same drug effect can be reduced, and the side effect of the drug can be effectively reduced, so that the preparation of the slow release material for controlling the release process of the drug in a human body is an urgent need in clinical medical treatment at present.

Ibuprofen (IBU) is a typical anti-inflammatory, analgesic and antipyretic drug commonly used in life, is used for drug loading due to the characteristics of low solubility and small molecular weight in an aqueous solution, and is a typical drug in a drug controlled release test. Montmorillonite (MMT) is a common layered silicate non-metal nano mineral, has the rigidity, thermal stability, dimensional stability and the like of inorganic matters, is widely applied to novel composite materials, and because the inorganic montmorillonite is directly added into a polymer material, the prepared composite material is difficult to meet the requirements of actual industrial production due to poor compatibility, so that the montmorillonite is necessary to be optimized and modified. The modified montmorillonite is added into the polymer matrix, so that the performance of the montmorillonite is more excellent, and the research lays a foundation for the application of montmorillonite in industrialization. Cellulose is a natural polymer with the largest reserve in nature, and only about 0.2% of cellulose is currently used. Carboxymethyl cellulose, which is the product of substitution of the carboxymethyl groups of cellulose, forms polymers that are either completely soluble or insoluble, depending on molecular weight and degree of substitution. Carboxymethyl cellulose forms a high viscosity colloid, solution, and has a series of properties such as thickening, flowing, emulsifying and dispersing, acid resistance, salt resistance, suspension, etc., and is most commonly used because it is physiologically harmless. High-end substitute products of carboxymethyl cellulose (CMC), namely polyanionic cellulose (PAC) and anionic cellulose ether, have higher substitution degree and substitution uniformity, shorter molecular chains, more stable molecular structures, salt resistance, acid resistance, calcium resistance, high temperature resistance and the like, and stronger dissolubility, but the products are widely applied to the fields of drinking water, industrial water, sewage treatment and the like. Starch is widely used in drug delivery systems because of its characteristics of good biocompatibility and degradability, environmental friendliness, low contamination, and the like. At present, no report related to the ibuprofen intercalation montmorillonite/starch/cellulose compound exists.

Disclosure of Invention

The invention aims to provide an ibuprofen intercalated montmorillonite/starch/cellulose compound capable of realizing slow release of ibuprofen and a preparation method thereof

In order to achieve the purpose, the technical scheme of the invention is as follows:

the preparation method of the ibuprofen intercalated montmorillonite/starch/cellulose compound comprises the following steps:

1) dissolving ibuprofen in absolute ethyl alcohol, fully dissolving the ibuprofen, and adding deionized water and montmorillonite powder to prepare a suspension;

2) under the condition of stirring, adding soluble starch and carboxymethyl cellulose into the suspension, placing the suspension in a water bath kettle, heating and stirring for reaction, then cooling to room temperature, centrifuging the product, collecting the solid, and drying to obtain the ibuprofen intercalated montmorillonite/starch/cellulose compound.

The mass ratio of the ibuprofen to the montmorillonite to the soluble starch to the carboxymethyl cellulose is 4:0.45-0.55:0.45-0.55: 0.26-0.27.

Further, the mass ratio of the ibuprofen, the montmorillonite, the soluble starch and the carboxymethyl cellulose is 4:0.5:0.5: 0.267.

The temperature of the heating and stirring reaction in the water bath kettle is 55-65 ℃, and the time is 7.5-8.5 hours.

Preferably, the montmorillonite is modified montmorillonite, and the preparation method is as follows: according to the fixation of montmorillonite and hydrochloric acid solutionMixing the two in a liquid ratio of 1g to 50mL, heating and stirring the mixture in an oil bath kettle for reaction, cooling and layering the mixture, removing supernatant, washing a filter cake with deionized water, carrying out suction filtration to neutrality, and drying the filter cake to obtain the modified montmorillonite. The compound prepared by adopting the modified montmorillonite is marked as ibuprofen intercalated montmorillonite (H)⁺) Starch/cellulose composite.

In the preparation process of the modified montmorillonite, the mass fraction of the hydrochloric acid solution is 15%. The temperature of the heating and stirring reaction in the oil bath kettle is 75-85 ℃, and the time is 7.5-8.5 hours.

The invention adopts the technical scheme, takes ibuprofen as a main body, takes montmorillonite (preferably modified montmorillonite), starch and cellulose as objects, prepares the IBU intercalated compound, researches the structure of the compound, and researches the release effect of IBU by using different buffer solutions and physiological saline. The experimental results show that: the IBU in the compound can generate a slow release effect in the solution, the release stage processes are a quick release stage, a slow release stage and a balance stage, the slow release performance of the compound added with the cellulose is improved, the concentration of the medicine in a human body can be kept, the administration frequency is reduced, and the side effect brought by the medicine is reduced.

Drawings

FIG. 1 is a UV absorption spectrum of IBU in a phosphate buffered solution at pH 6.6;

FIG. 2 is a standard curve of IBU in phosphate buffered saline at pH 6.6;

FIG. 3 is a UV absorption spectrum of IBU in phosphate buffered saline at pH 7.4;

FIG. 4 is a standard curve of IBU in phosphate buffered saline at pH 7.4;

FIG. 5 is a UV absorption spectrum of IBU in 0.9% physiological saline;

FIG. 6 is a standard curve of IBU in 0.9% normal saline;

FIG. 7 is an IR spectrum of the complex; wherein, a-montmorillonite/starch/cellulose compound; b-IBU intercalated montmorillonite/starch/cellulose composite; c-IBU intercalated montmorillonite (H +)/starch/cellulose complex;

FIG. 8 is an XRD pattern of the composite; wherein, a-IBU intercalates montmorillonite (H +)/starch/cellulose complex; b-IBU intercalated montmorillonite/starch/cellulose composite; c-montmorillonite/starch/cellulose complex;

FIG. 9 is a TG curve of ibuprofen intercalated montmorillonite/starch/cellulose composite; wherein, a-IBU intercalation montmorillonite/starch/cellulose compound; b-IBU intercalated montmorillonite (H)⁺) A/starch/cellulose complex;

FIG. 10 is the R-t curve of ibuprofen intercalated montmorillonite/starch/cellulose composite in different solutions; wherein, a-a buffer solution with pH 6.6; b-buffer solution with pH 7.4; c-0.9% physiological saline

FIG. 11 is an electron micrograph of montmorillonite;

FIG. 12 is an electron micrograph of a montmorillonite starch/cellulose composite;

FIG. 13 is an electron micrograph of an IBU intercalated montmorillonite/starch/cellulose composite;

FIG. 14 shows IBU intercalated montmorillonite (H)⁺) Electron micrograph of/starch/cellulose complex;

figure 15 is a first order kinetic fit equation for ibuprofen intercalated montmorillonite/starch/cellulose composite in phosphate buffered saline at pH 6.6;

figure 16 is a first order kinetic fit equation for ibuprofen intercalated montmorillonite/starch/cellulose composite in phosphate buffered saline at pH 7.4; figure 17 is a first order kinetic fit equation for ibuprofen intercalated montmorillonite/starch/cellulose composite in 0.9% normal saline.

Detailed Description