Method for preparing hydroxypropyl cellulose-mesoporous silica composite material with sustained-release performance
By preparing hydroxypropyl cellulose-mesoporous silica composite materials, the problem of burst release of hydroxypropyl cellulose was solved, achieving precise controlled release and sustained release of the drug, and improving dispersion efficiency and biocompatibility.
Patent Information
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- HANGZHOU FUYUAN ADVANCED MATERIALS TECHNOLOGY CO LTD
- Filing Date
- 2026-04-03
- Publication Date
- 2026-06-02
AI Technical Summary
In existing technologies, hydroxypropyl cellulose is difficult to use for precise controlled release of drugs and active substances, and is prone to burst release, which can lead to a sudden increase in concentration and cause adverse reactions.
A composite material with sustained-release properties is prepared by combining hydroxypropyl cellulose with mesoporous silica. The process includes steps such as ultrasonic dispersion, centrifugation, and freeze-drying to form a hydroxypropyl cellulose-mesoporous silica composite material, which is then mixed with drugs or active substances to achieve loading.
It prolongs the duration of action of drugs or active substances, improves dispersion efficiency, adjusts pore size to adapt to different active substances, has good biocompatibility, has a significant sustained-release effect, and the release rate is low within 48 hours.
Smart Images
Figure CN122124284A_ABST
Abstract
Description
Technical Field
[0001] This invention relates to the field of composite material preparation technology, and in particular to a method for preparing a hydroxypropyl cellulose-mesoporous silica composite material with sustained-release properties. Background Technology
[0002] In numerous industries such as pharmaceuticals and cosmetics, the demand for high-performance excipients is increasing daily. Hydroxypropyl cellulose (HCP) possesses many excellent properties for medical applications. It is an environmentally friendly, biocompatible, and abundant natural polymer derivative. Its molecular structure contains numerous hydroxyl groups, which can form complexes with drug molecules and bioactive substances through hydrogen bonds. It also exhibits excellent hydrophilicity, film-forming properties, adhesiveness, and thermoresponsiveness, making it irreplaceable in medical applications such as pharmaceutical formulation, ophthalmic treatment, and tissue repair. Mesoporous silica, with its regular nanoscale pore structure (pore size between 2-50 nm), large specific surface area, and pore volume, provides ample loading sites for drugs and active substances, enabling efficient loading and uniform dispersion of HCP and various drugs and active molecules. Its chemical properties are stable. Therefore, preparing a composite material from HCP and mesoporous silica is expected to combine the advantages of both, meeting the demand for high-performance excipients in multiple fields.
[0003] However, in practical applications such as pharmaceutical tablets and cosmetics, hydroxypropyl cellulose alone cannot achieve precise controlled release of drugs and active substances, and is prone to burst release, which not only reduces the therapeutic and usage effects, but may also cause adverse reactions due to a sudden increase in concentration. This contradicts the clinical drug use requirements of "precise delivery and reduced side effects" as well as the application requirements of mild cosmetics. Summary of the Invention
[0004] This invention proposes a method for preparing a hydroxypropyl cellulose-mesoporous silica composite material with sustained-release properties, which solves the problems of precise controlled release of hydroxypropyl cellulose in the prior art, the easy occurrence of burst release, and adverse reactions caused by a sudden increase in concentration.
[0005] The technical solution of this invention is implemented as follows: A method for preparing a hydroxypropyl cellulose-mesoporous silica composite material with sustained-release properties, comprising: Hydroxypropyl cellulose, mesoporous silica, and water or organic reagents are mixed and dispersed by ultrasonication to obtain a pre-dispersion liquid, and stirred at room temperature to obtain a dispersion liquid; the dispersion liquid is centrifuged or rotary evaporated to obtain a dried precursor; the dried precursor is freeze-dried or oven-dried, and then ground and sieved to obtain a hydroxypropyl cellulose-mesoporous silica composite material.
[0006] In some embodiments, the hydroxypropyl cellulose-mesoporous silica composite material is mixed with a drug or active substance to obtain hydroxypropyl cellulose-mesoporous silica loaded with the drug or active substance.
[0007] In some embodiments, the hydroxypropyl cellulose-mesoporous silica loaded with drugs or active substances is prepared as follows: The hydroxypropyl cellulose-mesoporous silica composite material is added to an aqueous or organic solution of a drug or active substance, stirred at room temperature, centrifuged, and freeze-dried to obtain the final product.
[0008] In some embodiments, the drug is ibuprofen, coenzyme Q10, aspirin, azithromycin, indomethacin, curcumin, etc., and the active substance is ectoine, arbutin, or nicotinamide.
[0009] In some embodiments, the ratio of the hydroxypropyl cellulose-mesoporous silica composite material, the drug, and the active substance / organic reagent added is (0.15-30g):(5-30mg / mL); the stirring time is 5h-2d; and the centrifugation speed is 4000-10000rpm.
[0010] In some embodiments, the ratio of hydroxypropyl cellulose, mesoporous silica, water, or organic reagent added is hydroxypropyl cellulose: mesoporous silica: water / organic reagent = (0.06-42g): (0.06-30g): (8-30000mL); the organic solution is composed of a drug or active substance and an organic reagent, wherein the organic reagent is ethanol, methanol, or acetone.
[0011] In some embodiments, the mesoporous silica is prepared as follows: A silicon source is mixed with a nonpolar organic solvent as a precursor solution. Water, a cationic surfactant, and an organic base are mixed, heated, and stirred to form a homogeneous aqueous phase system. The precursor solution is slowly added to the aqueous phase system, and the reaction is carried out under constant temperature conditions with stirring. After the reaction is completed, the lower aqueous phase is subjected to solid-liquid separation, and the supernatant is discarded to obtain a solid product. The solid product is washed, dried, and then subjected to programmed temperature calcination to obtain mesoporous silica. The calcination conditions are: a heating rate of 1-2℃ / min, a calcination temperature of 400-600℃, and a calcination time of 18-24 hours.
[0012] In some embodiments, the cationic surfactant is hexadecyltrimethylammonium bromide or hexadecyltrimethylammonium chloride; the organic base is triethanolamine or ammonia; the silicon source is tetraethyl orthosilicate; and the nonpolar organic solvent is cyclohexane or n-hexane. The ratio of water, cationic surfactant, organic base, silicon source, and nonpolar organic solvent added is (60-80g):(2-10g):(1-7g):(1-10mL):(5-30mL).
[0013] In some embodiments, the mesoporous silica is one of three-dimensional dendrites, SBA-15, and HMSNs.
[0014] In some embodiments, the ultrasonic treatment time is 30-50 min, and the temperature is 20-30℃; the stirring speed is 450-1500 rpm; the centrifugation speed is 4000-10000 rpm, and the time is 10-30 min; the rotary evaporation temperature is 20-50℃, and the rotation speed is 40-80 rpm; the sieving screen is 80-100 mesh.
[0015] In some embodiments, the freeze-drying conditions are: pre-freezing temperature -60℃ to -40℃; sublimation drying temperature -20℃ to 0℃; and desorption drying temperature 10-25℃.
[0016] Compared with the prior art, the present invention has the following advantages: (1) The present invention extends the duration of action of drugs or active substances by combining hydroxypropyl cellulose with mesoporous silica.
[0017] (2) The present invention can accelerate the dispersion process of hydroxypropyl cellulose in solvent and improve its dispersion efficiency.
[0018] (3) The mesoporous silica used in this invention has a high specific surface area, adjustable pore size, is compatible with different active substances or drugs, and has good biocompatibility.
[0019] (4) The present invention has a significant sustained-release effect, and the release rate is still very low within 48 hours. Attached Figure Description
[0020] To more clearly illustrate the technical solutions in the embodiments of the present invention or the prior art, the drawings used in the description of the embodiments or the prior art will be briefly introduced below. Obviously, the drawings described below are only some embodiments of the present invention. For those skilled in the art, other drawings can be obtained from these drawings without creative effort.
[0021] Figure 1 A scanning electron microscope image of the mesoporous silica prepared in Example 1; Figure 2 The image shows an electron microscope image of the mesoporous silica-hydroxypropyl cellulose composite material prepared in Example 1. Figure 3 Comparative water dispersion diagrams of hydroxypropyl cellulose and the mesoporous silica-hydroxypropyl cellulose composite material prepared in Example 1.
[0022] Figure 4 This is the standard curve for coenzyme Q10.
[0023] Figure 5 The release curve of coenzyme Q10 loaded on mesoporous silica prepared in Example 1.
[0024] Figure 6 The release curve of coenzyme Q10 loaded onto the hydroxypropyl cellulose-mesoporous silica composite material prepared in Example 1. Detailed Implementation
[0025] The technical solutions in the embodiments of the present invention will be clearly and completely described below. Obviously, the described embodiments are only some embodiments of the present invention, and not all embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of the present invention.
[0026] For simplicity, this paper only explicitly discloses some numerical ranges. However, any lower limit can be combined with any upper limit to form an undefined range; and any lower limit can be combined with other lower limits to form an undefined range, just as any upper limit can be combined with any other upper limit to form an undefined range. Furthermore, although not explicitly stated, every point or individual value between the endpoints of a range is included within that range. Therefore, each point or individual value can serve as its own lower or upper limit and be combined with any other point or individual value, or with other lower or upper limits, to form an undefined range.
[0027] Example 1 A method for preparing a hydroxypropyl cellulose-mesoporous silica composite material with sustained-release properties, comprising: (1) Preparation of mesoporous silica First, 2 mL of tetraethyl orthosilicate and 20 mL of cyclohexane were mixed as a precursor solution. Then, 70 mL of pure water, 8 g of hexadecyltrimethylammonium bromide, and 1 g of triethanolamine were dispersed in a reaction vessel. The temperature was controlled at 60 °C, and the mixture was stirred for 2 hours to form a homogeneous aqueous phase system. The precursor solution was slowly added to the aqueous solution along the wall, and the reaction was carried out under constant temperature conditions with stirring at 300 rpm for 24 hours. After the reaction was completed, the lower aqueous phase was separated into solid and liquid phases, and the supernatant was discarded to obtain a solid product. The solid product was washed, dried at 80 °C for 24 hours, and then subjected to programmed temperature calcination at a heating rate of 1 °C / min and a calcination temperature of 500 °C for 24 hours to obtain mesoporous silica material.
[0028] (2) Preparation of hydroxypropyl cellulose-mesoporous silica composite material Weigh 14g of hydroxypropyl cellulose into an Erlenmeyer flask, add 800mL of ethanol, and sonicate at 20kHz and 300W for 45min. Then pour the mixture into a 2L beaker. Next, weigh 10g of the mesoporous silica obtained in step (1) and add it to the 2L beaker. Sonicate at 20kHz and 300W for 45min, continue stirring at 900rpm for 3h at room temperature, centrifuge at 5000rpm for 20min, and freeze-dry. The freeze-drying temperature is pre-freezing at -60℃, sublimation drying at -20℃, and desorption drying at 10℃. The precipitate after freeze-drying is a white powder of hydroxypropyl cellulose-mesoporous silica. The powder is then refined in a mortar and sieved using a 100-mesh sieve.
[0029] (3) Preparation of hydroxypropyl cellulose-mesoporous silica composite material loaded with coenzyme Q10 1 g of hydroxypropyl cellulose-mesoporous silica composite material was weighed and dispersed in 1 mg / mL ethanol solution. The mixture was stirred at room temperature for 24 h at a stirring speed of 600 rpm, centrifuged at 10000 rpm for 10 min, and then lyophilized. The lyophilization temperature was -55℃ for pre-freezing, -10℃ for sublimation drying, and 15℃ for desorption drying. After lyophilization, hydroxypropyl cellulose-mesoporous silica composite material loaded with coenzyme Q10 was obtained.
[0030] Table 1. Changes in specific surface area before and after compositing mesoporous silica with hydroxypropyl cellulose-mesoporous silica. Table 1. Changes in specific surface area ; Characterization of nanocomposites Characterization of mesoporous silica and hydroxypropyl cellulose-mesoporous silica composites The morphology of mesoporous silica was systematically observed using scanning electron microscopy (SEM). Figure 1SEM images show that the original mesoporous silica nanospheres exhibit a monodisperse spherical structure with obvious pore structures on the surface. Further composite with hydroxypropyl cellulose can be visualized through SEM images (…). Figure 2 The presence of hydroxypropyl cellulose filling the pores of the composite material proves that the hydroxypropyl cellulose-mesoporous silica composite material has been successfully prepared.
[0031] This invention utilizes a fully automated specific surface area and porosity analyzer to determine the specific surface area of mesoporous silica and hydroxypropyl cellulose-mesoporous silica composites (Table 1). The data show that the specific surface area of the hydroxypropyl cellulose-mesoporous silica composite is significantly smaller than that of mesoporous silica (731 μm²). 2 / g decreased to 270.33m 2 / g, proving the successful composite of hydroxypropyl cellulose and mesoporous silica.
[0032] Experiment on the dispersibility of mesoporous silica in water for promoting hydroxypropyl cellulose Accurately weigh equal masses of mesoporous silica and the hydroxypropyl cellulose-mesoporous silica composite material prepared in Example 1 using an analytical balance, add 5 mL of deionized water to each, add the weighed samples to the test tubes in sequence, sonicate both test tubes simultaneously for 10 min, and then observe their dissolution.
[0033] ( Figure 3 Experiments showed that after 10 minutes of sonication, some pure hydroxypropyl cellulose remained undissolved on the water surface, while the hydroxypropyl cellulose-mesoporous silica mixture was uniformly dispersed in the water. This indicates that adding mesoporous materials helps to increase the dispersion time of hydroxypropyl cellulose in water.
[0034] Comparative release behavior experiment of hydroxypropyl cellulose loaded with coenzyme Q10 and hydroxypropyl cellulose-mesoporous silica composite material This invention utilizes ultraviolet-visible absorption spectroscopy to conduct comparative release tests on hydroxypropyl cellulose-loaded and hydroxypropyl cellulose-mesoporous silica-loaded materials.
[0035] First, the maximum absorption wavelength of the coenzyme Q10 ethanol solution was determined using a UV spectrophotometer. A series of coenzyme Q10 ethanol standard solutions of different concentrations were then prepared, and a standard working curve was plotted (see...). Figure 4A certain amount of hydroxypropyl cellulose / coenzyme Q10 and hydroxypropyl cellulose-mesoporous silica / coenzyme Q10 were respectively prepared into initial solutions of 0.5 mg / mL in phosphate buffered saline (PBS) at pH 7.4. In vitro simulated release was performed in 15 mL vials at room temperature with magnetic stirring (200 rpm). 500 μL of the solution was taken at regular intervals, and its absorbance at 275 nm was measured. The same volume of PBS was then added to the release solution to maintain a constant volume. Changes in absorbance were continuously monitored. The results showed that pure cellulose released a higher concentration within 48 hours. However, the release of hydroxypropyl cellulose-mesoporous silica was lower within the same time frame, indicating low drug release efficiency. This confirms that the hydroxypropyl cellulose-mesoporous silica composite material has a sustained-release effect.
[0036] Finally, it should be noted that the above embodiments are only used to illustrate the technical solutions of the present invention, and not to limit them; although the present invention has been described in detail with reference to the foregoing embodiments, those skilled in the art should understand that modifications can still be made to the technical solutions described in the foregoing embodiments, or equivalent substitutions can be made to some or all of the technical features; and these modifications or substitutions do not cause the essence of the corresponding technical solutions to deviate from the scope of the technical solutions of the embodiments of the present invention.
Claims
1. A method for preparing a hydroxypropyl cellulose-mesoporous silica composite material with sustained-release properties, characterized in that, include: Hydroxypropyl cellulose, mesoporous silica, water, and organic reagents were mixed and dispersed by ultrasonication to obtain a pre-dispersion, which was then stirred at room temperature to obtain a dispersion. The dispersion is centrifuged or rotary evaporated to obtain a dried precursor; the dried precursor is freeze-dried or oven-dried, and then ground and sieved to obtain a hydroxypropyl cellulose-mesoporous silica composite material.
2. The method for preparing a hydroxypropyl cellulose-mesoporous silica composite material with sustained-release properties according to claim 1, characterized in that, The hydroxypropyl cellulose-mesoporous silica composite material is mixed with a drug or active substance to obtain hydroxypropyl cellulose-mesoporous silica loaded with the drug or active substance.
3. The method for preparing a hydroxypropyl cellulose-mesoporous silica composite material with sustained-release properties according to claim 2, characterized in that, The preparation method of the hydroxypropyl cellulose-mesoporous silica loaded with drugs or active substances is as follows: The hydroxypropyl cellulose-mesoporous silica composite material is added to an aqueous or organic solution of a drug or active substance, stirred at room temperature, centrifuged, and freeze-dried to obtain the final product.
4. The method for preparing a hydroxypropyl cellulose-mesoporous silica composite material with sustained-release properties according to claim 3, characterized in that, The drug is ibuprofen, coenzyme Q10, aspirin, azithromycin, indomethacin, or curcumin, and the active substance is ectoine, arbutin, or nicotinamide.
5. The method for preparing a hydroxypropyl cellulose-mesoporous silica composite material with sustained-release properties according to claim 3, characterized in that, The ratio of the added hydroxypropyl cellulose-mesoporous silica composite material, drug, and active substance / organic reagent is (0.15-30g):(5-30mg / mL); the stirring time is 5h-2d; the centrifugation speed is 4000-10000rpm; the organic solution is composed of drug or active substance and organic reagent, wherein the organic reagent is ethanol, methanol, or acetone.
6. The method for preparing a hydroxypropyl cellulose-mesoporous silica composite material with sustained-release properties according to claim 1, characterized in that, The ratio of hydroxypropyl cellulose, mesoporous silica, water or organic reagent added is hydroxypropyl cellulose: mesoporous silica: water / organic reagent = (0.06-42g): (0.06-30g): (8-30000mL).
7. A method for preparing a hydroxypropyl cellulose-mesoporous silica composite material with sustained-release properties according to claim 1 or 2, characterized in that, The method for preparing mesoporous silica is as follows: A silicon source is mixed with a nonpolar organic solvent as a precursor solution; water, a cationic surfactant, and an organic base are mixed, heated, and stirred to form a homogeneous aqueous phase system; the precursor solution is slowly added to the aqueous phase system, and the reaction is carried out under constant temperature conditions with stirring; after the reaction is completed, the lower aqueous phase is separated into solid and liquid phases, the supernatant is discarded, and a solid product is obtained; the solid product is washed, dried, and then subjected to programmed temperature calcination to obtain mesoporous silica.
8. The method for preparing a hydroxypropyl cellulose-mesoporous silica composite material with sustained-release properties according to claim 7, characterized in that, The cationic surfactant is hexadecyltrimethylammonium bromide or hexadecyltrimethylammonium chloride; the organic base is triethanolamine or ammonia; the silicon source is tetraethyl orthosilicate; the nonpolar organic solvent is cyclohexane or n-hexane; the ratio of water, cationic surfactant, organic base, silicon source, and nonpolar organic solvent is (60-80g): (2-10g): (1-7g): (1-10mL): (5-30mL).
9. A method for preparing a hydroxypropyl cellulose-mesoporous silica composite material with sustained-release properties according to claim 1 or 2, characterized in that, The mesoporous silica is one of three-dimensional dendrites, SBA-15, and HMSNs.
10. A method for preparing a hydroxypropyl cellulose-mesoporous silica composite material with sustained-release properties according to claim 1 or the present invention, characterized in that, The ultrasonic treatment time is 30-50 min, and the temperature is 20-30℃; the stirring speed is 450-1500 rpm; the centrifugation speed is 4000-10000 rpm, and the time is 10-30 min; the rotary evaporation temperature is 20-50℃, and the rotation speed is 40-80 rpm; the freeze-drying conditions are: pre-freezing temperature -60℃ to -40℃; sublimation drying temperature -20℃ to 0℃; and desorption drying temperature 10-25℃.