Drug carrier for treating rheumatism as well as preparation method and application thereof
By using drug carriers composed of SiO2 and Fe3O4 materials, the problems of small loading and difficult to target in the prior art are solved, and high loading and targeting are achieved, reducing side effects and improving drug utilization.
Patent Information
- Application Number
- CN202411518420.9
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2024-10-29
- Publication Date
- 2025-01-14
AI Technical Summary
Existing rheumatoid drugs have side effects and the drug carriers such as mesoporous silica have a small load, making it difficult to effectively carry the drug to the target position.
Using a drug carrier composed of SiO2 material and Fe3O4 material, the Fe3O4 material is located inside the SiO2 material to form a cavity structure to increase the drug load and use the magnetism of Fe3O4 to achieve the targeting of the drug.
It improves drug loading and targeting, controls drug release speed, reduces drug frequency and side effects, and enhances drug biocompatibility.
Smart Images
Figure CN119303101A_ABST
Abstract
Description
Technical Field
[0001] The invention belongs to the technical field of biomaterials, and in particular relates to a drug carrier for treating rheumatism, a preparation method and application thereof. Background Art
[0002] Rheumatism is a group of diseases that mainly attack joints, muscles, blood vessels, bones and other related soft tissues, and has attracted much attention in the field of modern medicine. Its onset is usually hidden and progresses slowly, and the course of the disease is often long. In addition, most rheumatic diseases are also hereditary, which makes people with rheumatic disease in their families face a higher risk of disease.
[0003] At present, rheumatic diseases are mainly treated with drugs, mainly including non-steroidal anti-inflammatory drugs, glucocorticoids, and disease-modifying anti-rheumatic drugs. However, these drugs have certain side effects. For example, although non-steroidal anti-inflammatory drugs can relieve pain and inflammation to a certain extent, long-term use may cause adverse effects on organs such as the gastrointestinal tract and kidneys. Although glucocorticoids have powerful anti-inflammatory and immunosuppressive effects, long-term high-dose use can lead to side effects such as osteoporosis, hypertension, and diabetes. In addition, the mechanism of action of disease-modifying anti-rheumatic drugs is relatively complex, the bioavailability is relatively low, and the onset time is longer.
[0004] Drug carriers can change the way drugs enter the human body, control the release rate of drugs, and improve the utilization rate of drugs. This can reduce the frequency of medication and alleviate drug side effects. Mesoporous silica materials have the advantages of being non-toxic, adjustable pore size, and high specific surface area. They are a satisfactory drug carrier that has been widely studied in recent years. However, mesoporous silica also has certain limitations. For example: the drug loading capacity of mesoporous silica is small, and how mesoporous silica drug carriers carry drugs to the target location, etc. Summary of the invention
[0005] The present invention overcomes the disadvantages of the prior art and provides a drug carrier for treating rheumatism, a preparation method and an application thereof. The drug carrier has a large drug loading capacity and is targeted.
[0006] The technical solution adopted by the present invention to solve its technical problem is:
[0007] The present invention provides a drug carrier for treating rheumatism, comprising: SiO2 material and Fe3O4 material, wherein the SiO2 material is a spherical hollow structure, the Fe3O4 material is a solid sphere, the Fe3O4 material is inside the SiO2 material, and there is a cavity structure between the Fe3O4 material and the inner wall of the SiO2 material.
[0008] The drug carrier is composed of SiO2 material and Fe3O4 material, which is non-toxic and has good biocompatibility. Fe3O4 material is magnetic and can give the drug targeting. The Fe3O4 material is inside the SiO2 material, and there is a cavity structure between the Fe3O4 material and the inner wall of the SiO2 material. The cavity structure has a large specific surface area and can fully adsorb the drug to increase the drug loading capacity.
[0009] The present invention also provides a method for preparing a drug carrier for treating rheumatism, comprising the following steps:
[0010] S1. Disperse commercially available Fe3O4 particles in anhydrous ethanol and stir vigorously, then add tetraethyl orthosilicate, ammonia water and N-[3-(trimethoxysilyl)propyl]ethylenediamine and stir at room temperature for 5 to 8 hours;
[0011] S2, adding tetraethyl orthosilicate to step S1, and continuing to stir and react for 5 to 8 hours;
[0012] S3. Then, 0.5-2 mL of 40% HF acid was added to step S1, and the mixture was stirred for 30 min. The particles were then adsorbed by a magnet, the solution was discarded, and the drug carrier was obtained after washing twice with 20 mL of anhydrous ethanol and 20 mL of deionized water.
[0013] In the preparation method, step S1 is to form a layer of organic-inorganic hybrid SiO2 material on the outer layer of Fe3O4 particles, and the SiO2 structure is relatively loose. The tetraethyl orthosilicate added in step S2 can continue to form a dense SiO2 shell under the condition that ammonia water is used as a catalyst in step S1.
[0014] The HF acid in step S3 can etch SiO2. Normally, the outermost SiO2 shell will be etched first. However, the inner SiO2 is a loose structure of organic-inorganic hybrids, which is more easily etched by HF acid, resulting in HF acid etching the inner SiO2 first. After the reaction is completed, a Fe3O4 core and a SiO2 shell will be formed, and there will be a cavity structure between the shell and the core.
[0015] The preparation method is further preferred as a drug carrier for treating rheumatism.
[0016] Preferably, the size of the Fe3O4 particles in step S1 is 120-150 nm.
[0017] If the size of Fe3O4 particles is too small, the price will be high, which will increase the cost. If the size is too large, the specific surface area will be reduced, resulting in a decrease in the drug loading capacity of the prepared drug carrier.
[0018] Preferably, the added amounts of Fe3O4 particles, anhydrous ethanol, tetraethyl orthosilicate, ammonia water and N-[3-(trimethoxysilyl)propyl]ethylenediamine in step S1 are: 0.2 g, 100 mL, 1-2 mL, 2-4 mL and 0.2-1 mL, respectively.
[0019] Preferably, the amount of tetraethyl orthosilicate added in step S2 is 2 to 4 mL.
[0020] The invention also provides an application of a drug carrier for treating rheumatism.
[0021] 30 mg of drug carrier was added to 20 mL of propylene glycol and stirred for 15 min, then 5-10 mg of glucocorticoid was added and stirred for 12 h, then the drug was collected with a magnet and washed three times with deionized water to remove unbound drug and dried at room temperature.
[0022] Compared with the prior art, the present invention has the following beneficial effects:
[0023] (1) Compared with traditional drug release, drug carriers can control the release rate of drugs and improve the utilization rate of drugs, thereby reducing the frequency of drug use and alleviating drug side effects.
[0024] (2) Compared with mesoporous SiO2 drug carriers, hollow SiO2 has a larger inner cavity structure and can carry more drugs.
[0025] (3) The drug carrier is combined with magnetic Fe3O4 to make it magnetic, which can make the drug magnetically oriented, thereby improving the targeting of the drug.
[0026] (4) When synthesizing the drug carrier, its structure is cleverly designed so that it can ensure the SiO2 cavity structure while containing the Fe3O4 core structure. BRIEF DESCRIPTION OF THE DRAWINGS
[0027] Figure 1 It is a flow chart of the preparation of drug carriers for treating rheumatism;
[0028] Figure 2 is a transmission electron microscope photograph of the drug carrier for treating rheumatism prepared in Example 1;
[0029] Figure 3 is the N2 adsorption-desorption isotherm of the drug carrier powder for treating rheumatism prepared in Example 1;
[0030] Figure 4 are the results obtained by the vibrating sample magnetometer of the drug carriers prepared in the comparative example and Examples 1-3;
[0031] Figure 5It is a bar graph of the drug loading of the drug carriers of the comparative example and Examples 4-6;
[0032] Figure 6 It is the drug release rate curve of the drug carrier of comparative example and Examples 4-6. DETAILED DESCRIPTION
[0033] The present invention will be further described below in conjunction with embodiments and comparative examples.
[0034] Example 1
[0035] This embodiment provides a method for preparing a drug carrier for treating rheumatism, comprising the following steps:
[0036] S1. Disperse 0.2 g of commercially available Fe3O4 particles with a size of 120 nm in 100 mL of anhydrous ethanol and stir vigorously. Then add 1 mL of tetraethyl orthosilicate, 2 mL of ammonia water and 0.2 mL of N-[3-(trimethoxysilyl)propyl]ethylenediamine and stir at room temperature for 5 h.
[0037] S2, add 2 mL of tetraethyl orthosilicate to step S1, and continue stirring the reaction for 5 h;
[0038] S3. Then, 0.5 mL of 40% HF acid was added to step S1, and the mixture was stirred for 30 min. The particles were then adsorbed by a magnet, the solution was discarded, and the drug carrier was obtained after washing twice with 20 mL of anhydrous ethanol and 20 mL of deionized water.
[0039] According to the above method, a drug carrier for treating rheumatism is obtained.
[0040] Example 2
[0041] This embodiment provides a method for preparing a drug carrier for treating rheumatism, comprising the following steps:
[0042] S1. Disperse 0.2 g of commercially available Fe3O4 particles with a size of 130 nm in 100 mL of anhydrous ethanol and stir vigorously. Then add 1.5 mL of tetraethyl orthosilicate, 3 mL of ammonia water and 0.5 mL of N-[3-(trimethoxysilyl)propyl]ethylenediamine and stir at room temperature for 6 h.
[0043] S2, add 3 mL of tetraethyl orthosilicate to step S1, and continue stirring the reaction for 6 hours;
[0044] S3. Then, 1 mL of 40% HF acid was added to step S1, and the mixture was stirred for 30 min. The particles were then adsorbed by a magnet, the solution was discarded, and the drug carrier was obtained after washing twice with 20 mL of anhydrous ethanol and 20 mL of deionized water.
[0045] According to the above method, a drug carrier for treating rheumatism is obtained.
[0046] Example 3
[0047] This embodiment provides a method for preparing a drug carrier for treating rheumatism, comprising the following steps:
[0048] S1. Disperse 0.2 g of commercially available Fe3O4 particles with a size of 150 nm in 100 mL of anhydrous ethanol and stir vigorously. Then add 2 mL of tetraethyl orthosilicate, 4 mL of ammonia water and 1 mL of N-[3-(trimethoxysilyl)propyl]ethylenediamine and stir at room temperature for 8 h.
[0049] S2, add 4 mL of tetraethyl orthosilicate to step S1, and continue stirring the reaction for 8 h;
[0050] S3. Then, 2 mL of 40% HF acid was added to step S1, and the mixture was stirred for 30 min. The particles were then adsorbed by a magnet, the solution was discarded, and the drug carrier was obtained after washing twice with 20 mL of anhydrous ethanol and 20 mL of deionized water.
[0051] According to the above method, a drug carrier for treating rheumatism is obtained.
[0052] Example 4
[0053] This embodiment provides a method for preparing a combination of a drug carrier for treating rheumatism and a drug for treating rheumatism, comprising the following steps:
[0054] 30 mg of the drug carrier prepared in Example 1 was added to 20 mL of propylene glycol and stirred for 15 min, then 5 mg of glucocorticoid was added and stirred for 12 h, then the drug was collected with a magnet and washed three times with deionized water to remove unbound drug and dried at room temperature.
[0055] Example 5
[0056] This embodiment provides a method for preparing a combination of a drug carrier for treating rheumatism and a drug for treating rheumatism, comprising the following steps:
[0057] 30 mg of the drug carrier prepared in Example 1 was added to 20 mL of propylene glycol and stirred for 15 min, then 8 mg of glucocorticoid was added and stirred for 12 h, then the drug was collected with a magnet and washed three times with deionized water to remove unbound drug and dried at room temperature.
[0058] Example 6
[0059] This embodiment provides a method for preparing a combination of a drug carrier for treating rheumatism and a drug for treating rheumatism, comprising the following steps:
[0060] 30 mg of the drug carrier prepared in Example 1 was added to 20 mL of propylene glycol and stirred for 15 min, then 10 mg of glucocorticoid was added and stirred for 12 h, then the drug was collected with a magnet and washed three times with deionized water to remove unbound drug and dried at room temperature.
[0061] Comparative Example
[0062] This embodiment provides a preparation method of a mesoporous SiO2 particle drug carrier combined with a drug for treating rheumatism, comprising the following steps:
[0063] 30 mg of commercially available 120 nm mesoporous SiO2 particles were added to 20 mL of propylene glycol and stirred for 15 min, followed by the addition of 10 mg of glucocorticoids and stirring for 12 h. The drugs were then collected with a magnet and washed three times with deionized water to remove unbound drugs and dried at room temperature.
[0064] Figure 1 This is a flow chart for the preparation of drug carriers for treating rheumatism, which allows a more intuitive view of the preparation process of the drug carriers.
[0065] Figure 2 It is a transmission electron microscope photo of the drug carrier for treating rheumatism prepared in Example 1. It can be seen that the SiO2 material is a spherical hollow structure, the Fe3O4 material is a solid sphere, the Fe3O4 material is inside the SiO2 material, and there is a cavity structure between the Fe3O4 material and the SiO2 material inner wall. This also explains that in the synthesis process, HF acid will first etch the internal organic-inorganic hybrid SiO2, thereby forming a cavity structure. In addition, the Fe3O4 material has magnetism and can give the targeting of the drug. The Fe3O4 material is inside the SiO2 material, and there is a cavity structure between the Fe3O4 material and the SiO2 material inner wall. The cavity structure has a large specific surface area, can fully adsorb drugs, and improve the loading capacity of the drug.
[0066] Figure 3 This is the N2 adsorption-desorption isotherm of the drug carrier powder for treating rheumatism prepared in Example 1. It can be seen that the drug carrier has a higher specific surface area and can adsorb and carry more drugs.
[0067] Figure 4 The results obtained by the vibrating sample magnetometer of the drug carriers prepared in the comparative example and Examples 1-3 show that the comparative example has almost no magnetism, while the prepared drug carriers all have certain magnetism. The transport direction of the drug can be changed by magnetic permeability, so that the drug has certain targeting.
[0068] Figure 5It is a bar graph of the drug loading of the drug carriers of the comparative example and Examples 4-6. It can be seen that the drug loading of the mesoporous SiO2 particles is lower than that of the drug carriers prepared in Examples 5 and 6, and the lower drug loading in Example 4 is due to the smaller amount of drug added. Under the same conditions, the drug carrier prepared by the present invention has a higher drug loading.
[0069] Figure 6 The drug release rate curves of the drug carriers of the comparative example and Examples 4 to 6 are shown in FIG. 1. As can be seen, the drug carriers prepared in the present invention release drugs more slowly and have a longer duration of action.
[0070] It can be seen from the experimental results of the above comparative example and Examples 1-6 that the present invention has prepared a drug carrier for treating rheumatism.
[0071] Those skilled in the art should understand that the above are only some specific embodiments of the present invention, rather than all embodiments. It should be noted that for those of ordinary skill in the art, many modifications and improvements can be made, and all modifications or improvements that do not exceed the scope of protection of the present invention should be regarded as the scope of protection of the present invention.
Claims
1. A drug carrier for treating rheumatism, comprising: SiO2 material and Fe3O4 material, characterized in that the SiO2 material is a spherical hollow structure, the Fe3O4 material is a solid sphere, the Fe3O4 material is inside the SiO2 material, and there is a cavity structure between the Fe3O4 material and the inner wall of the SiO2 material.
2. A method for preparing the drug carrier for treating rheumatism according to claim 1, characterized in that: The following steps are involved: S1. Disperse commercially available Fe3O4 particles in anhydrous ethanol and stir vigorously, then add tetraethyl orthosilicate, ammonia water and N-[3-(trimethoxysilyl)propyl]ethylenediamine and stir at room temperature for 5 to 8 hours; S2, adding tetraethyl orthosilicate to step S1, and continuing to stir and react for 5 to 8 hours; S3. Then, 0.5-2 mL of 40% HF acid was added to step S1, and the mixture was stirred for 30 min. The particles were then adsorbed by a magnet, the solution was discarded, and the drug carrier was obtained after washing twice with 20 mL of anhydrous ethanol and 20 mL of deionized water.
3. The method for preparing a drug carrier for treating rheumatism according to claim 2, characterized in that The size of the Fe3O4 particles described in step S1 is 120-150 nm.
4. The method for preparing a drug carrier for treating rheumatism according to claim 2, characterized in that The added amounts of Fe3O4 particles, anhydrous ethanol, tetraethyl orthosilicate, ammonia water and N-[3-(trimethoxysilyl)propyl]ethylenediamine described in step S1 are: 0.2 g, 100 mL, 1-2 mL, 2-4 mL and 0.2-1 mL, respectively.
5. The method for preparing a drug carrier for treating rheumatism according to claim 2, characterized in that: The amount of tetraethyl orthosilicate added in step S2 is 2 to 4 mL.
6. A method for preparing the combination of the drug carrier for treating rheumatism and the drug for treating rheumatism according to claim 1, characterized in that: The following steps are involved: 30 mg of drug carrier was added to 20 mL of propylene glycol and stirred for 15 min, then 5-10 mg of glucocorticoid was added and stirred for 12 h, then the drug was collected with a magnet and washed three times with deionized water to remove unbound drug and dried at room temperature.
7. Use of a drug carrier for treating rheumatism obtained by the preparation method according to claim 6 in the field of rheumatism.