CN113876963B - Preparation method of aspirin-silicon dioxide slow-release body - Google Patents
Preparation method of aspirin-silicon dioxide slow-release body Download PDFInfo
- Publication number
- CN113876963B CN113876963B CN202111160143.5A CN202111160143A CN113876963B CN 113876963 B CN113876963 B CN 113876963B CN 202111160143 A CN202111160143 A CN 202111160143A CN 113876963 B CN113876963 B CN 113876963B
- Authority
- CN
- China
- Prior art keywords
- silicon dioxide
- aspirin
- water
- solution
- aqueous solution
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Active
Links
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
- A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
- A61K47/54—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic compound
- A61K47/541—Organic ions forming an ion pair complex with the pharmacologically or therapeutically active agent
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/60—Salicylic acid; Derivatives thereof
- A61K31/612—Salicylic acid; Derivatives thereof having the hydroxy group in position 2 esterified, e.g. salicylsulfuric acid
- A61K31/616—Salicylic acid; Derivatives thereof having the hydroxy group in position 2 esterified, e.g. salicylsulfuric acid by carboxylic acids, e.g. acetylsalicylic acid
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
- A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
- A61K47/52—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an inorganic compound, e.g. an inorganic ion that is complexed with the active ingredient
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F7/00—Compounds containing elements of Groups 4 or 14 of the Periodic System
- C07F7/02—Silicon compounds
- C07F7/08—Compounds having one or more C—Si linkages
- C07F7/0834—Compounds having one or more O-Si linkage
- C07F7/0838—Compounds with one or more Si-O-Si sequences
- C07F7/0872—Preparation and treatment thereof
- C07F7/0874—Reactions involving a bond of the Si-O-Si linkage
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
- Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
Abstract
The invention discloses a preparation method of an aspirin-silicon dioxide slow-release body, which comprises the following steps: the preparation method comprises the steps of taking sodium silicate and inorganic acid as reaction raw materials, preparing silicon dioxide powder without adding a dispersing agent, immersing the mixture into an aspirin solution to prepare silicon dioxide containing aspirin, modifying the silicon dioxide containing aspirin by a dry method with hexamethyldisilazane as a modifying agent to prepare an aspirin-silicon dioxide slow-release body, performing grafting modification on the surface of the silicon dioxide loaded with aspirin, coating the aspirin with a grafting group skillfully, preparing steric hindrance, avoiding the aspirin from rapidly flowing out of a mesoporous structure after entering a human body, enabling the release rate of the aspirin to be stable, and realizing the long-acting release of the aspirin; partial hydroxyl groups on the surface of the silicon dioxide are replaced, so that the hygroscopicity of the silicon dioxide is reduced, meanwhile, the agglomeration of the silicon dioxide can be effectively inhibited, and the dispersibility of the silicon dioxide is improved; the mesoporous silica does not need a template agent, and the preparation process is simple and reliable.
Description
Technical Field
The invention belongs to the technical field of drug carriers, and particularly relates to a preparation method of an aspirin-silicon dioxide slow-release body.
Background
The slow release technology can realize stable administration for a long time, reduce the administration times of patients, reduce toxic and side effects and improve the bioavailability of the medicine, and is a research hot spot in the field of medicine in recent years, wherein a medicine carrier is one of the keys for realizing the slow release technology. In the past decades, various drug carriers, such as cyclodextrins, have been designed to reduce the interference of the immune system on the drugs in order to reduce the toxic side effects and low water solubility of the drugs, but the cyclodextrin system has weak action with the drug molecules, and the formed slow release body has low mechanical strength, weak drug carrying capacity and single response to environmental stimulus, can not well cope with complex pathological environments, and has a large limitation in clinical treatment.
The silicon dioxide material has better biocompatibility, the surface of the silicon dioxide material is rich in silicon hydroxyl groups, and the silicon dioxide material can be subjected to diversified chemical modification, and has been widely studied as a functional carrier of various medicines in recent years.
CN104188985 discloses a preparation method of targeted controlled release aspirin powder. The preparation process comprises the preparation of the magnetic core-shell nano silicon dioxide drug carrier, the partial dissolution of the magnetic core, the loading of aspirin on the magnetic drug carrier and the secondary coating of aspirin. The method has the advantages of better slow release effect, longer synthetic route, complex method and no contribution to practical application, and improves the long-acting slow release and controllable release efficiency by adopting acid dissolution and secondary coating of polyvinylpyrrolidone macromolecule sol.
CN104030296 discloses a preparation method of a micro-mesoporous hollow tubular silicon dioxide material and a micro-mesoporous silicon dioxide drug sustained-release material obtained by the method. The drug loading rate of the material to aspirin reaches 15%, but the release rate is too fast.
Disclosure of Invention
Aiming at the problems in the related art, the invention provides a preparation method of an aspirin-silicon dioxide slow-release body, which aims to overcome the technical problems existing in the prior related art.
The technical scheme of the invention is realized as follows:
a method for preparing an aspirin-silica slow release body, comprising the following steps:
(1) Taking water glass and inorganic acid as reaction raw materials, and preparing silicon dioxide powder without adding a dispersing agent;
(2) Immersing the silicon dioxide powder into an aspirin solution to prepare silicon dioxide containing aspirin;
(3) And (3) modifying the silicon dioxide containing the aspirin by a dry method by taking hexamethyldisilazane as a modifier to prepare the aspirin-silicon dioxide slow-release body.
The invention firstly utilizes cheap sodium silicate and inorganic acid to react to prepare the silicon dioxide rich in mesopores, then adopts the silicon dioxide to adsorb aspirin, and finally carries out grafting modification on the surface of the silicon dioxide loaded with the aspirin, thereby skillfully utilizing a grafting group to coat the aspirin, manufacturing steric hindrance, avoiding the aspirin from rapidly flowing out of a mesopore structure after entering a human body, ensuring stable release rate of the aspirin-silicon dioxide slow-release body medicament and realizing long-acting release.
The specific reaction formula of the modified grafting for silicon dioxide is as follows:
according to the reaction formula, hexamethyldisilazane is hydrolyzed on the surface of silicon dioxide, the hydroxyl of the silicon dioxide is replaced by trimethylsilyl, and the trimethylsilyl molecular structure forms an approximately umbrella-shaped shielding structure on the surface of the silicon dioxide to prevent the medicine from flowing out of the mesoporous of the silicon dioxide too quickly, so that the long-acting slow release effect is realized; on the other hand, the surface of the silicon dioxide is rich in hydroxyl groups, has stronger hydrophilicity, is extremely easy to absorb moisture, is difficult to disperse and wet in an organic phase, and forms grafting phenomenon among particles under the action of hydrogen bonds, so that the silicon dioxide is easy to agglomerate and extremely poor in dispersibility, and the characteristics are obviously unfavorable for subsequent drug processing and storage.
Secondly, most of the existing silica modification processes are wet modification, namely, the silica and the modified raw materials are placed in a liquid environment for stirring reaction, but the finished product after the wet modification needs to be subjected to separation and purification steps, the production steps are high in cost, and the finished product is easy to pollute in the process, so that the invention adopts dry modification; in addition, focusing on the present invention, the silica has been loaded with aspirin prior to modification grafting, and if wet modification is employed, it will result in some of the aspirin being lost to the liquid reaction system, and therefore conventional wet modification is clearly unsuitable for the present invention.
Finally, the existing silica preparation process is added with dispersing agents or other surfactants with dispersing and homogenizing functions, but the inventor finds that: if the anionic or cationic dispersing agent is added, the reaction system for synthesizing the silicon dioxide can be subjected to precipitation, so that the preparation of the silicon dioxide is influenced; however, since neutral dispersants cause silica to have a small pore diameter and neutral dispersants tend to aggregate on the surface of silica, and thus the silica is agglomerated, the inventors have surprisingly found that the addition of no dispersant is the only best choice.
Preferably, in the step (1), the water glass is prepared into a water glass aqueous solution by using distilled water as a base solution, the inorganic acid is prepared into an inorganic acid aqueous solution by using distilled water as a base solution, and then the inorganic acid aqueous solution is mixed to prepare the silicon dioxide, wherein in the process, the pH value is kept between 7 and 8, and meanwhile, stirring and heating are kept.
Diluting the synthetic raw materials by using a base solution, stirring and heating, so as to reduce the viscosity of a reaction system; in addition, the larger the oil absorption value of the silicon dioxide is, the better the performance of the silicon dioxide is, the larger the specific surface area and the pore volume of the silicon dioxide are, and the applicant finds that compared with other base solutions, the silicon dioxide with higher oil absorption value can be synthesized by adopting distilled water as the base solution, and the larger specific surface area and the pore volume are beneficial to subsequent aspirin loading.
Specifically, the modulus of the water glass is 3-4, the silicon dioxide content of the water glass water solution is 10-20wt%, the inorganic acid is sulfuric acid, and the water glass has the advantage of low price, and the sulfuric acid content of the sulfuric acid water solution is 20-30wt%.
Preferably, in the step (1), the water glass aqueous solution and the inorganic acid aqueous solution are added to the reaction vessel in a parallel flow mode to be mixed and reacted. In actual mass production, when one-way feeding is adopted to precipitate silicon dioxide, due to the large feeding amount, even if a high-speed stirrer is adopted, the gradual increase of the viscosity of the feed liquid is difficult to avoid, the fluidity of the feed liquid is rapidly reduced, and serious agglomeration phenomenon occurs.
The applicant also finds that the parallel flow duration can also influence the specific surface area of the silicon dioxide, and through experiments, the silicon dioxide with larger specific surface area can be prepared with the parallel flow duration of 30-120min, which is beneficial to drug loading.
Specifically, before the water glass aqueous solution and the inorganic acid aqueous solution are injected into the reaction container, part of base solution is injected into the reaction container, the temperature is raised to 40-60 ℃, the temperature of the feed solution after synthesizing silicon dioxide is raised to 70-90 ℃, and then the reaction container is aged and precipitated for 1-3 hours.
Preferably, in the step (1), ultrasonic agitation is used. The reason why ultrasonic agitation is particularly preferred in the present application is that: the synthesized silicon dioxide is required to be loaded with medicines subsequently, and the ultrasonic stirring can continuously generate the formation, growth and collapse of bubbles in a reaction system, the collapse of the bubbles can cause impact on the inside of the silicon dioxide with lower polycondensation degree, and part of chemical bonds are broken, so that the internal space of a silicon dioxide finished product is larger, and the medicine loading capacity is improved.
Preferably, in the step (1), the feed liquid obtained after the water glass aqueous solution and the inorganic acid aqueous solution are mixed and reacted is acidified and filtered to obtain a silica filter cake, and the silica filter cake is washed and made into dry powder.
The pH also affects the oil absorption of the silica, more preferably, the pH of the acidification is 2 to 4, which can be used to make silica with a higher oil absorption and improve the silica performance.
More preferably, the silica filter cake is washed by taking sulfuric acid with the concentration of 1wt% and distilled water as washing liquid, the content of sodium ions and sulfate radicals in the silica filter cake is reduced, and then the silica filter cake is dried to prepare powder.
Specifically, the pH of the feed liquid after the water glass aqueous solution and the inorganic acid aqueous solution are mixed and reacted is adjusted to be 2-4, the feed liquid is acidified and aged for at least 0.5h, the feed liquid is cooled to 60-70 ℃ and then filtered, and the operation that the silicon dioxide filter cake is made into powder is as follows: and uniformly dispersing the filter cake in a small amount of water again to prepare slurry, and drying in a spray drying mode to obtain the powder.
Specifically, the operation of step (2) is as follows: immersing the powder prepared in the step (1) into an aspirin solution until the adsorption is balanced, filtering and drying to prepare the aspirin-containing silicon dioxide.
Preferably, the specific operation of the step (3) is as follows: spreading the silicon dioxide containing aspirin in a vacuum drying oven to enlarge the contact area with hexamethyldisilazane, wherein the hexamethyldisilazane accounts for 1-10% of the mass of the silicon dioxide containing aspirin, the hexamethyldisilazane contacts the surface of the silicon dioxide containing aspirin in a gas form to carry out grafting modification, the temperature of the vacuum drying oven is set to be 30-40 ℃, and a vacuum pump is started for vacuum pumping after a certain period of reaction.
And (3) reacting in a vacuum drying oven to prevent the hexamethyldisilazane from being rapidly hydrolyzed to generate trimethylsilanol and hexamethyldisiloxane by contacting with air. The adsorption water on the surface of the silicon dioxide is dried at the low temperature of 30-40 ℃, and the adsorption water is adsorbed on the surface of the silicon dioxide due to the fact that the phenomenon that pores of the silicon dioxide are combined is caused by the fact that the drying temperature is too high, so that the pore volume is reduced, aspirin is extruded, and the drug loading is reduced.
Preferably, the grafting modification time is 1-6h, if the time is less than 1h, the methyldisilazane is not fully reacted with silicon dioxide, if the time is more than 6h, the exposed hydroxyl is mostly replaced by trimethylsilyl, and the rest small hydroxyl is increased due to the increase of trimethylsilyl with umbrella-shaped structure, so that the steric hindrance is increased, the contact with hexamethyldisilazane is not facilitated, the time is increased, and the grafting rate is not obviously improved.
The invention has the beneficial effects that:
(1) The invention firstly utilizes cheap sodium silicate and inorganic acid to react to prepare mesoporous silica, then adopts the silica to adsorb aspirin, and finally carries out grafting modification on the surface of the silica loaded with the aspirin, and skillfully utilizes a grafting group to coat the aspirin, thereby manufacturing steric hindrance, avoiding the aspirin from rapidly flowing out of a mesoporous structure after entering a human body, ensuring stable drug release rate and realizing long-acting release of the drug;
(2) According to the invention, the silicon dioxide is subjected to grafting modification, part of hydroxyl groups on the surface of the silicon dioxide are replaced, so that the hygroscopicity of the silicon dioxide is greatly reduced, the silicon dioxide is easy to store, meanwhile, the reduction of hydroxyl groups can effectively inhibit the recrystallization or reaggregation of the silicon dioxide, the dispersibility of the silicon dioxide is improved, and the silicon dioxide is convenient to further process in a later period;
(3) The mesoporous silica of the invention does not need a template agent, has simple and reliable preparation process, can be changed into other medicines according to the needs, and has wider application range.
Detailed Description
The technical solutions of the present invention will be clearly and completely described in connection with the embodiments, and it is obvious that the described embodiments are only some embodiments of the present invention, but not all embodiments. All other embodiments, which can be made by those skilled in the art based on the embodiments of the invention without making any inventive effort, are intended to be within the scope of the invention.
Example 1
(1) Preparing a water glass aqueous solution and a dilute sulfuric acid aqueous solution;
the water glass with the modulus of 3.35 is used as a raw material to prepare the water glass water solution with the silicon dioxide content of 20 weight percent, and the concentration of the dilute sulfuric acid water solution is 30 weight percent.
(2) And (3) injecting 50L of bottom water into the stirring reaction kettle at the temperature of 40 ℃, enabling 75 liters of water glass aqueous solution and dilute sulfuric acid aqueous solution to flow in parallel through a constant flow pump, keeping the pH value of the system to be neutral, enabling the parallel flow time to be 30 minutes, adjusting the temperature to 90 ℃ after the parallel flow is completed, and aging and precipitating for 1 hour.
(3) Adding dilute sulfuric acid into the feed liquid prepared in the step (2), regulating the pH value to 3, aging for 0.5 hour, cooling to 60 ℃, and filtering;
washing the filter cake with sulfuric acid with the concentration of 1wt%, mixing and washing with tap water and pure water, performing pressure filtration to obtain a silicon dioxide filter cake, uniformly dispersing the filter cake in a small amount of water again to obtain slurry, and performing spray drying to obtain powder.
The BET specific surface area of the silica powder obtained after drying was 346m 2 Per g, pore volume of 1.97cm 3 And/g, the average pore diameter is 22nm, and the mesoporous particles are mesoporous.
(4) 3.000g of the aspirin crude drug was weighed and dissolved in 150.0ml of absolute ethanol to obtain an aspirin ethanol solution. Adding 1.5000g of the silicon dioxide powder into the aspirin ethanol solution, adopting a dynamic adsorption mode, adsorbing for 24 hours to adsorption balance, and vacuum drying to obtain the silicon dioxide containing aspirin.
(5) Silica containing aspirin was vapor phase hydrophobized with hexamethyldisilazane: 100.000g of the aspirin-containing silicon dioxide is weighed and dried in vacuum and placed in a vacuum drying oven to be spread as much as possible, 6.000g of hexamethyldisilazane is weighed and placed in a surface dish and placed in the vacuum drying oven, the temperature of the vacuum drying oven is set to be 35 ℃, the treatment time is set to be 6 hours, and a vacuum pump is started to evacuate after the treatment is completed.
Comparative example
The aspirin-containing silica obtained in the step (4) of example 1 was used as a control (i.e., without being subjected to a vapor phase hydrophobic treatment).
Example 2
(1) Preparing a water glass aqueous solution and a dilute sulfuric acid aqueous solution;
the water glass with the modulus of 3.35 is used as a raw material to prepare the water glass water solution with the silicon dioxide content of 10 weight percent, and the concentration of the dilute sulfuric acid water solution is 20 weight percent.
(2) And (3) injecting 50L of bottom water into the stirring reaction kettle at the temperature of 60 ℃, enabling the water glass aqueous solution and the dilute sulfuric acid aqueous solution to flow in parallel by a constant flow pump by 75 liters, keeping the pH value of the system to be neutral, enabling the parallel flow time to be 30 minutes, adjusting the temperature to 70 ℃ after the parallel flow is completed, and aging and precipitating for 1 hour.
(3) Adding dilute sulfuric acid into the feed liquid prepared in the step (2), regulating the pH value to 3, aging for 0.5 hour, cooling to 70 ℃, and filtering;
washing the filter cake with sulfuric acid with the concentration of 1wt%, mixing and washing with tap water and pure water, performing pressure filtration to obtain a silicon dioxide filter cake, uniformly dispersing the filter cake in a small amount of water again to obtain slurry, and performing spray drying to obtain powder.
The BET specific surface area of the silica powder obtained after drying was 431m 2 Per g, pore volume of 1.61cm 3 And/g, the average pore diameter is 17nm, and the mesoporous particles are mesoporous.
(4) 3.000g of the aspirin crude drug was weighed and dissolved in 150.0ml of absolute ethanol to obtain an aspirin ethanol solution. Adding 1.5000g of the silicon dioxide powder into the aspirin ethanol solution, adopting a dynamic adsorption mode, adsorbing for 24 hours to adsorption balance, and vacuum drying to obtain the silicon dioxide containing aspirin.
(5) Silica containing aspirin was vapor phase hydrophobized with hexamethyldisilazane: 100.000g of the aspirin-containing silicon dioxide is weighed and dried in vacuum and placed in a vacuum drying oven to be spread as much as possible, 10.000g of hexamethyldisilazane is weighed and placed in a surface dish and placed in the vacuum drying oven, the temperature of the vacuum drying oven is set to be 40 ℃, the treatment time is 3 hours, and a vacuum pump is started to evacuate after the treatment is completed.
Example 3
(1) Preparing a water glass aqueous solution and a dilute sulfuric acid aqueous solution;
the water glass with the modulus of 3.35 is used as a raw material to prepare the water glass water solution with the silicon dioxide content of 15wt%, and the concentration of the dilute sulfuric acid water solution is 25wt%.
(2) And (3) injecting 50L of bottom water into the stirring reaction kettle at the temperature of 50 ℃, enabling 75 liters of water glass aqueous solution and dilute sulfuric acid aqueous solution to flow in parallel through a constant flow pump, keeping the pH value of the system to be neutral, enabling the parallel flow time to be 90 minutes, adjusting the temperature to 80 ℃ after the parallel flow is completed, and aging and precipitating for 1 hour.
(3) Adding dilute sulfuric acid into the feed liquid prepared in the step (2), regulating the pH value to 3, aging for 0.5 hour, cooling to 70 ℃, and filtering;
washing the filter cake with sulfuric acid with the concentration of 1wt%, mixing and washing with tap water and pure water, performing pressure filtration to obtain a silicon dioxide filter cake, uniformly dispersing the filter cake in a small amount of water again to obtain slurry, and performing spray drying to obtain powder.
The BET specific surface area of the silica powder obtained after drying was 381m 2 Per g, pore volume of 1.75cm 3 Per g, flatThe average pore diameter is 19nm, and is mesoporous.
(4) 3.000g of the aspirin crude drug was weighed and dissolved in 150.0ml of absolute ethanol to obtain an aspirin ethanol solution. Adding 1.5000g of the silicon dioxide powder into the aspirin ethanol solution, adopting a dynamic adsorption mode, adsorbing for 24 hours to adsorption balance, and vacuum drying to obtain the silicon dioxide containing aspirin.
(5) Silica containing aspirin was vapor phase hydrophobized with hexamethyldisilazane: 100.000g of the aspirin-containing silicon dioxide is weighed and dried in vacuum and placed in a vacuum drying oven to be spread as much as possible, 10.000g of hexamethyldisilazane is weighed and placed in a surface dish and placed in the vacuum drying oven, the temperature of the vacuum drying oven is set to be 30 ℃, the treatment time is 1h, and a vacuum pump is started to evacuate after the treatment is completed.
1. Ultraviolet absorbance was measured using an ethanol solution of aspirin of known concentration, a standard curve of the relation between the absorbance and the concentration of aspirin in the ethanol solution was drawn, and the adsorption amount of aspirin per gram of silica powder of examples 1 to 3 was calculated, and examples 1 and comparative example were 1.13g/g of SiO 2 Example 2 was 0.79g/g of SiO 2 And example 3 was 0.91g/g of SiO 2 。
2. Drug release tests were performed on examples 1-3 and the control:
(1) The preparation method for preparing the physiological fluid simulating the human body environment comprises the following steps: weighing 0.24g KH 2 PO 4 ，3.63g Na 2 HPO 4 ·12H 2 O,8g NaCl and 0.2g KCl are dissolved in 900mL deionized water, the pH=7.4 is regulated, and deionized water is added to a volume of 1000mL;
(2) Weighing 0.1000g of the aspirin-silicon dioxide slow-release body after vacuum drying, placing the slow-release body in a conical flask, adding 100mL of physiological fluid simulating human body environment, placing the slow-release body in a constant-temperature shaking table at 37 ℃, and setting the rotating speed to 150rpm/min;
(3) 2X 1.8mL of the solution was removed by a pipette at 6h,12h,18h,24h,36h,48h, and centrifuged in a refrigerated centrifuge at a speed of 11000rpm and a temperature of 37 ℃.
(4) Taking supernatant, measuring ultraviolet absorbance by using aspirin simulated physiological fluid with known concentration, drawing a standard curve of relation between absorbance and concentration of aspirin in the simulated physiological fluid, and calculating drug release amounts of comparative examples and examples 1-3, wherein the result is as follows:
from the above table, the drug loading of examples 1 to 3 is sufficient, and the long-acting slow release effect is achieved; the modified grafted silica, which is available through the drug release behavior of comparative example and example 1, achieves encapsulation of aspirin with excellent long-acting sustained release effects.
3. The procedure of example 1 for preparing silica was repeated, and comparative experiments were performed with PEG-6000, chitosan, PVP as the dispersing agent and without dispersing agent, respectively, according to the chemical industry standard HG/T3072-2008: determination of dibutyl phthalate (DBP) absorption to determine oil absorption.
The experimental results are: the oil absorption value of the silica added with PEG-6000 is 3.12, the oil absorption value of the silica added with chitosan is 3.24, the oil absorption value of the silica added with PVP is 3.19, the oil absorption value of the silica without the dispersing agent is 3.52, and the comparison of the result data shows that the silica with larger oil absorption value, namely larger specific surface area and pore volume and more aspirin can be prepared without the dispersing agent.
4. The preparation process of the silicon dioxide prepared in the embodiment 1 is repeated, distilled water, 50% ethanol water solution and absolute ethanol are respectively used as base solutions to prepare water glass water solution and sulfuric acid water solution, and comparative experiments are carried out on the distilled water, the 50% ethanol water solution and the absolute ethanol water solution according to the chemical industry standard HG/T3072-2008: determination of dibutyl phthalate (DBP) absorption to determine oil absorption.
The experimental results are: the oil absorption value of the silica prepared by using distilled water as base solution is 3.61, the oil absorption value of the silica prepared by using 50% ethanol water solution as base solution is 3.52, the oil absorption value of the silica prepared by using absolute ethanol water solution as base solution is 3.49, and the comparison of the result data shows that the silica with larger oil absorption value, namely larger specific surface area and pore volume, can be prepared by using distilled water as base solution, thereby being beneficial to loading more aspirin.
5. And testing whether the dispersibility of the modified silicon dioxide is improved:
dimethyl sulfoxide (DMSO) is a common organic solvent for pharmaceutical preparation, and therefore, DMSO and water were chosen as test solvents for this test.
Taking 0.2g of the example 1 and the comparative example respectively, adding 20mL of water respectively, stirring for 40 minutes by ultrasonic, standing and cooling, and observing the state of the mixed solution; then, 0.2g of each of example 1 and comparative example was taken, 20mL of silicone oil was added thereto, and the mixture was stirred with ultrasound for 40 minutes, allowed to stand and cooled, and then observed for the state of the mixture.
The results were as follows:
the hydrophobicity is better improved, the agglomeration phenomenon is obviously improved, the dispersibility is improved, and the particle distribution is more uniform, so that the modified silicon dioxide has the advantages that part of hydroxyl groups on the surface of the silicon dioxide are replaced by organic branched chains, the hydroxyl groups on the surface of the silicon dioxide are reduced, and the hydrogen bonding effect among the silicon dioxide is further weakened.
Variations and modifications to the above would be obvious to persons skilled in the art to which the invention pertains from the foregoing description and teachings. Therefore, the invention is not limited to the specific embodiments disclosed and described above, but some modifications and changes of the invention should be also included in the scope of the claims of the invention. In addition, although specific terms are used in the present specification, these terms are for convenience of description only and do not limit the present invention in any way.
Claims (3)
1. A method for preparing an aspirin-silica slow release body, which is characterized by comprising the following steps:
(1) On the premise of not adding a dispersing agent, water glass and inorganic acid are used as reaction raw materials to prepare silicon dioxide powder in a synthesizing way;
the water glass is prepared into water glass aqueous solution by taking distilled water as base solution, the inorganic acid is prepared into inorganic acid aqueous solution by taking distilled water as base solution, the water glass aqueous solution and the inorganic acid aqueous solution are added into a reaction vessel in a parallel flow mode for mixing reaction, the parallel flow time is 30-120min, and then the mixture is mixed to synthesize the prepared silicon dioxide;
the modulus of the water glass is 3-4, the silicon dioxide content of the water glass water solution is 10-20wt%, the inorganic acid is sulfuric acid, and the sulfuric acid content of the sulfuric acid water solution is 20-30wt%;
acidifying and filtering the feed liquid after the water glass aqueous solution and the inorganic acid aqueous solution are mixed and reacted, wherein the pH value of the acidification is 2-4 to obtain a silicon dioxide filter cake, and then washing the silicon dioxide filter cake to prepare dry powder;
the silica filter cake is washed by taking sulfuric acid with the concentration of 1wt% and distilled water as washing liquid, and then dried to prepare powder;
(2) Immersing the silicon dioxide powder into an aspirin solution to prepare silicon dioxide containing aspirin;
(3) Using hexamethyldisilazane as a modifier, and modifying the silicon dioxide containing aspirin by a dry method to prepare an aspirin-silicon dioxide slow-release body;
the specific operation of the step (3) is as follows: and (3) placing the silicon dioxide containing aspirin in a vacuum drying oven for spreading, and enabling the hexamethyldisilazane to contact the surface of the silicon dioxide containing aspirin in a gas form to carry out graft modification, wherein the temperature of the vacuum drying oven is set to be 30-40 ℃.
2. The method according to claim 1, wherein in the step (1), ultrasonic agitation is used.
3. The method of claim 1, wherein the grafting modification is for a period of time ranging from 1 to 6 hours.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202111160143.5A CN113876963B (en) | 2021-09-30 | 2021-09-30 | Preparation method of aspirin-silicon dioxide slow-release body |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202111160143.5A CN113876963B (en) | 2021-09-30 | 2021-09-30 | Preparation method of aspirin-silicon dioxide slow-release body |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN113876963A CN113876963A (en) | 2022-01-04 |
| CN113876963B true CN113876963B (en) | 2023-07-25 |
Family
ID=79004681
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202111160143.5A Active CN113876963B (en) | 2021-09-30 | 2021-09-30 | Preparation method of aspirin-silicon dioxide slow-release body |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN113876963B (en) |
Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102702245A (en) * | 2012-06-20 | 2012-10-03 | 中国科学院上海硅酸盐研究所 | Hydrophobic mesoporous nanomaterial and preparation method and application thereof |
| CN104188917A (en) * | 2014-09-11 | 2014-12-10 | 天津市职业大学 | Preparation method of controlled-release aspirin powder |
| CN107854449A (en) * | 2017-09-20 | 2018-03-30 | 中山大学 | A kind of composite nano-microsphere with medicine controlled releasing performance and its preparation method and application |
| CN108793173A (en) * | 2018-08-01 | 2018-11-13 | 中国科学技术大学 | A method of improved silica aerogel material is prepared using outer circulation mode constant pressure and dry |
| CN112452294A (en) * | 2020-11-03 | 2021-03-09 | 中山大学附属口腔医院 | Preparation method of mesoporous silica particles with adjustable mesoporous aperture |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FR2833937B1 (en) * | 2001-12-26 | 2004-11-12 | Rhodia Chimie Sa | SILICA WITH LOW WATER RESUME |
| US8097269B2 (en) * | 2004-02-18 | 2012-01-17 | Celonova Biosciences, Inc. | Bioactive material delivery systems comprising sol-gel compositions |
-
2021
- 2021-09-30 CN CN202111160143.5A patent/CN113876963B/en active Active
Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102702245A (en) * | 2012-06-20 | 2012-10-03 | 中国科学院上海硅酸盐研究所 | Hydrophobic mesoporous nanomaterial and preparation method and application thereof |
| CN104188917A (en) * | 2014-09-11 | 2014-12-10 | 天津市职业大学 | Preparation method of controlled-release aspirin powder |
| CN107854449A (en) * | 2017-09-20 | 2018-03-30 | 中山大学 | A kind of composite nano-microsphere with medicine controlled releasing performance and its preparation method and application |
| CN108793173A (en) * | 2018-08-01 | 2018-11-13 | 中国科学技术大学 | A method of improved silica aerogel material is prepared using outer circulation mode constant pressure and dry |
| CN112452294A (en) * | 2020-11-03 | 2021-03-09 | 中山大学附属口腔医院 | Preparation method of mesoporous silica particles with adjustable mesoporous aperture |
Also Published As
| Publication number | Publication date |
|---|---|
| CN113876963A (en) | 2022-01-04 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Akbari et al. | Synthesis of poly (ethylene glycol)(PEG) grafted silica nanoparticles with a minimum adhesion of proteins via one-pot one-step method | |
| Liu et al. | Formation and characterization of natural polysaccharide hollow nanocapsules via template layer-by-layer self-assembly | |
| Chen et al. | Cyclodextrin-based metal–organic framework nanoparticles as superior carriers for curcumin: Study of encapsulation mechanism, solubility, release kinetics, and antioxidative stability | |
| Kazemzadeh et al. | Structure-property relationship for different mesoporous silica nanoparticles and its drug delivery applications: A review | |
| Qian et al. | Zwitterionic polymer chain-assisted lysozyme imprinted core-shell carbon microspheres with enhanced recognition and selectivity | |
| Timin et al. | Preparation and surface properties of mesoporous silica particles modified with poly (N-vinyl-2-pyrrolidone) as a potential adsorbent for bilirubin removal | |
| CN104800169A (en) | Method for preparing magnetic-targeted sustained/controlled release carrier of hydrophobic drug by adopting chitosan and beta-cyclodextrin | |
| Nguyen et al. | Surface PEGylation of hollow mesoporous silica nanoparticles via aminated intermediate | |
| JP2013542157A (en) | Production of irregular porous silicon dioxide material and application of fatty alcohol polyoxyethylene ether in its production | |
| Dement’Eva et al. | A new method for loading mesoporous silica nanoparticles with drugs: Sol–gel synthesis using drug micelles as a template | |
| Zhang et al. | Selective binding of heparin oligosaccharides in a magnetic thermoresponsive molecularly imprinted polymer | |
| AU2014356854B2 (en) | Process for producing inorganic particulate material | |
| CN113425854A (en) | Anisic acid and polyethyleneimine modified tumor-targeted mesoporous silica nanoparticles, and preparation method and application thereof | |
| Yang et al. | Multifunctional mesoporous silica nanoparticles with different morphological characteristics for in vitro cancer treatment | |
| CN113562737B (en) | Mesoporous silica nanoparticle with adjustable chiral structure and preparation method and application thereof | |
| CN113876963B (en) | Preparation method of aspirin-silicon dioxide slow-release body | |
| Kapusuz | Sol–gel derived silica/polyethylene glycol hybrids as potential oligonucleotide vectors | |
| Gan et al. | Effects of microsize on the biocompatibility of UiO67 from protein-adsorption behavior, hemocompatibility, and histological toxicity | |
| CN114276681A (en) | Polydopamine microsphere with multilevel mesoporous structure and preparation method thereof | |
| CN111217372A (en) | Chiral mesoporous core-shell structure silica nanoparticle and preparation method and application thereof | |
| Kim et al. | Releasing properties of proteins on SBA-15 spherical nanoparticles functionalized with aminosilanes | |
| Yu et al. | pH-responsive gelatin polymer-coated silica-based mesoporous composites for the sustained-release of indomethacin | |
| Trofin et al. | Synthesis of Crosslinked Microparticles Based on Glycidyl Methacrylate and N‐Vinylimidazole | |
| KR100859763B1 (en) | Hydrophobicity Control Process of Silica Particle Using Trialkoxysilane Comprising Unsubstituted Alkyl Group, Alkenyl Group, or Alkynyl Group and Silica Particle thereby | |
| CN112156730B (en) | Preparation method of high-purity monodisperse porous silicon oxide spheres |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| TA01 | Transfer of patent application right |
Effective date of registration: 20230625 Address after: 701-702, Tian'an science and technology exchange center, Panyu energy saving science and Technology Park, 555 Panyu Avenue North, Panyu District, Guangzhou, Guangdong 511400 Applicant after: GUANGZHOU LINGWE TECHNOLOGY CO.,LTD. Applicant after: LENGSHUIJIANG THREE A NEW MATERIAL TECHNOLOGY CO.,LTD. Address before: 701-702, Tian'an science and technology exchange center, Panyu energy saving science and Technology Park, 555 Panyu Avenue North, Panyu District, Guangzhou, Guangdong 511400 Applicant before: GUANGZHOU LINGWE TECHNOLOGY CO.,LTD. |
|
| TA01 | Transfer of patent application right | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant |