CN114949239A - Preparation method and application of multifunctional joint synovial fluid additive - Google Patents
Preparation method and application of multifunctional joint synovial fluid additive Download PDFInfo
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- 230000000996 additive effect Effects 0.000 title claims abstract description 28
- 210000001179 synovial fluid Anatomy 0.000 title claims abstract description 27
- 238000002360 preparation method Methods 0.000 title claims abstract description 18
- 239000013310 covalent-organic framework Substances 0.000 claims abstract description 53
- VYFYYTLLBUKUHU-UHFFFAOYSA-N dopamine Chemical compound NCCC1=CC=C(O)C(O)=C1 VYFYYTLLBUKUHU-UHFFFAOYSA-N 0.000 claims abstract description 22
- 239000003814 drug Substances 0.000 claims abstract description 18
- 238000011068 loading method Methods 0.000 claims abstract description 14
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- 206010003246 arthritis Diseases 0.000 claims abstract description 11
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- 238000000034 method Methods 0.000 claims abstract description 8
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- 239000000178 monomer Substances 0.000 claims description 21
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 18
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- 239000002244 precipitate Substances 0.000 claims description 14
- 239000000047 product Substances 0.000 claims description 14
- 229910021642 ultra pure water Inorganic materials 0.000 claims description 13
- 239000012498 ultrapure water Substances 0.000 claims description 13
- SNLFYGIUTYKKOE-UHFFFAOYSA-N 4-n,4-n-bis(4-aminophenyl)benzene-1,4-diamine Chemical compound C1=CC(N)=CC=C1N(C=1C=CC(N)=CC=1)C1=CC=C(N)C=C1 SNLFYGIUTYKKOE-UHFFFAOYSA-N 0.000 claims description 11
- 239000011259 mixed solution Substances 0.000 claims description 11
- -1 2-ethylhexyl Chemical group 0.000 claims description 9
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- 239000003937 drug carrier Substances 0.000 claims description 6
- 239000002260 anti-inflammatory agent Substances 0.000 claims description 4
- RZEKVGVHFLEQIL-UHFFFAOYSA-N celecoxib Chemical compound C1=CC(C)=CC=C1C1=CC(C(F)(F)F)=NN1C1=CC=C(S(N)(=O)=O)C=C1 RZEKVGVHFLEQIL-UHFFFAOYSA-N 0.000 claims description 4
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- JGMJQSFLQWGYMQ-UHFFFAOYSA-M sodium;2,6-dichloro-n-phenylaniline;acetate Chemical group [Na+].CC([O-])=O.ClC1=CC=CC(Cl)=C1NC1=CC=CC=C1 JGMJQSFLQWGYMQ-UHFFFAOYSA-M 0.000 claims description 4
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- FCYISTSRTMTMQZ-UHFFFAOYSA-N 5-[2,5-bis(2-ethylhexyl)-4-(5-formylthiophen-2-yl)-3,6-dioxopyrrolo[3,4-c]pyrrol-1-yl]thiophene-2-carbaldehyde Chemical compound CCCCC(CC)CN1C(=O)C2=C(C=3SC(C=O)=CC=3)N(CC(CC)CCCC)C(=O)C2=C1C1=CC=C(C=O)S1 FCYISTSRTMTMQZ-UHFFFAOYSA-N 0.000 claims 1
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Images
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- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08G—MACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS
- C08G12/00—Condensation polymers of aldehydes or ketones with only compounds containing hydrogen attached to nitrogen
- C08G12/02—Condensation polymers of aldehydes or ketones with only compounds containing hydrogen attached to nitrogen of aldehydes
- C08G12/40—Chemically modified polycondensates
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- 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
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
- A61K31/19—Carboxylic acids, e.g. valproic acid
- A61K31/195—Carboxylic acids, e.g. valproic acid having an amino group
- A61K31/196—Carboxylic acids, e.g. valproic acid having an amino group the amino group being directly attached to a ring, e.g. anthranilic acid, mefenamic acid, diclofenac, chlorambucil
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- 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
- A61K31/63—Compounds containing para-N-benzenesulfonyl-N-groups, e.g. sulfanilamide, p-nitrobenzenesulfonyl hydrazide
- A61K31/635—Compounds containing para-N-benzenesulfonyl-N-groups, e.g. sulfanilamide, p-nitrobenzenesulfonyl hydrazide having a heterocyclic ring, e.g. sulfadiazine
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- 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
- A61K47/56—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 macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule
- A61K47/59—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 macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyureas or polyurethanes
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- A—HUMAN NECESSITIES
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/19—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles lyophilised, i.e. freeze-dried, solutions or dispersions
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
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- C08G12/00—Condensation polymers of aldehydes or ketones with only compounds containing hydrogen attached to nitrogen
- C08G12/02—Condensation polymers of aldehydes or ketones with only compounds containing hydrogen attached to nitrogen of aldehydes
- C08G12/04—Condensation polymers of aldehydes or ketones with only compounds containing hydrogen attached to nitrogen of aldehydes with acyclic or carbocyclic compounds
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Abstract
The invention discloses a preparation method of a multifunctional joint lubricating additive, which synthesizes a covalent organic framework with photo-thermal conversion performance by a simple method, further improves the dispersion stability and near-infrared absorption function of the covalent organic framework through dopamine modification, adsorbs anti-inflammatory drugs by utilizing the non-covalent bond effect, and improves the wear resistance and friction reduction performance of bionic joint synovial fluid by taking the anti-inflammatory drugs as joint synovial fluid additives. The lubricant additive has the advantages of simple synthesis, good near-infrared light responsiveness, low cytotoxicity, high drug loading, good slow release effect and the like, has a good effect on the treatment of arthritis, and can greatly prolong the lubrication life of joint synovial fluid.
Description
Technical Field
The invention belongs to the technical field of mechanical engineering and biological engineering, and particularly relates to a preparation method and application of a multifunctional joint synovial fluid additive.
Background
Arthritis is a common chronic disease, and according to incomplete statistics, about 50% of the aged over 60 years of age in our country have arthritis diseases of varying degrees. Arthritis causes cartilage degeneration, inflammation and destruction of tissues around joints, and the deterioration of the disease condition further causes deformity, disability and the like, thereby seriously affecting the life and health of patients. Studies have demonstrated that cartilage friction and wear from inadequate joint lubrication are important causes of joint inflammation. Clinically, the main component of joint lubricating fluid commonly used at present is hyaluronic acid, but the joint lubricating fluid has the problems of insufficient bearing load and easy degradation, and particularly, the generated large amount of free radicals are accelerated along with the aggravation of the inflammation of joint parts. Hyaluronic acid is degraded, so that patients need to be supplemented by regular injection, and the pain of the patients is increased. Therefore, the research on the joint lubricant with the functions of lubricating and treating the inflammation simultaneously has important significance on the treatment and improvement of the joint inflammation or the quality of life.
Covalent Organic Frameworks (COFs) are an emerging crystalline porous material that not only has high chemical and physical stability, but also has a high specific surface area and good biocompatibility. Compared with the existing nano lubricating material, COF has the following advantages: (1) different monomers can be selected according to requirements for design and synthesis: COF monomers are mainly linked through strong covalent bonds, and the COF monomers are various in types and have rich designability. (2) In the friction process, the COF can quickly form a lubricating film to reduce friction under the action of high shear generated by friction, so that excellent wear-resistant and friction-reducing properties are achieved. (3) The high specific surface area and the porous structure enable the composite material to have strong adsorption capacity, and can load various anti-inflammatory drugs, thereby realizing the treatment of inflammation.
However, at present, no COF is used as a joint lubricating additive, and meanwhile, no published report of loading anti-inflammatory drugs is provided, and no synthetic preparation technology is established.
Disclosure of Invention
In order to solve the technical problems, the invention provides a novel COF-based joint synovial fluid additive which not only has excellent friction reduction and wear resistance and photothermal conversion performance, but also can load arthritis treatment drugs through adsorption. Compared with pure water, the addition of the lubricating additive reduces the friction coefficient by 78.3 percent, and has good biocompatibility and inflammation treatment effect.
The invention provides a preparation method of the multifunctional joint synovial fluid additive.
The technical scheme adopted by the invention is as follows:
reacting a 3, 6-bis (5-aldehyde thiophene-2-yl) -2, 5-bis (2-ethylhexyl) pyrrolo [3,4-c ] pyrrole-1, 4 (2H, 5H) -diketone monomer with a tris (4-aminophenyl) amine monomer to obtain a covalent organic framework material, modifying the covalent organic framework material by using dopamine, and loading arthritis treatment drugs to obtain the covalent organic framework nano drug carrier joint synovial fluid additive.
The structural formula of the covalent organic framework material is as follows:
the preparation method of the joint synovial fluid additive comprises the following steps:
(1) preparation of specific covalent organic framework materials: adding a 3, 6-bis (5-aldehyde thiophene-2-yl) -2, 5-bis (2-ethylhexyl) pyrrolo [3,4-c ] pyrrole-1, 4 (2H, 5H) -diketone monomer into a beaker, and then adding chloroform for dissolving to obtain a reddish purple solution A; adding a tri (4-aminophenyl) amine monomer into a beaker, and dissolving with methanol to obtain a solution B with light brown color; uniformly mixing the solution A and the solution B, stirring, dropwise adding glacial acetic acid serving as a catalyst, and reacting for 48 hours at room temperature; centrifuging after 48 h to remove supernatant to obtain blue-green precipitate, washing the precipitate with tetrahydrofuran, and centrifuging until the supernatant becomes colorless; obtaining a product COF;
(2) modification of specific covalent organic framework materials: ultrasonically dispersing the COF product into ultrapure water, adding dopamine, adjusting the pH value of the mixed solution, and stirring at a constant speed in the dark; centrifuging the mixed solution to remove supernatant, and repeatedly centrifuging with ultrapure water for 3 times; vacuum freeze drying to obtain modified covalent organic framework COF-PDA;
(3) and loading the medicine for treating arthritis on COF-PDA to obtain the compound joint synovial fluid additive.
Preferably, the mass ratio of 3, 6-bis (5-aldehyde thiophen-2-yl) -2, 5-bis (2-ethylhexyl) pyrrolo [3,4-c ] pyrrole-1, 4 (2H, 5H) -dione to chloroform in step (1) is: 2:1, the mass volume of glacial acetic acid and tris (4-aminophenyl) amine is 15 ml: 50 mg.
Preferably, the rotation speed of the centrifugation in the step (1) is 5000-8000 r/min, and the time is 5-20 min;
in the step (2), the dosage of DA added in every 100 mg of COF is 20-50 mg;
in the step (2), the pH value of the mixed solution is 8.5.
The covalent organic framework prepared by the preparation method is spherical with the size of 80-150 nm.
The invention provides application of the joint synovial fluid additive in preparing a joint synovial fluid medicament.
The invention provides application of the joint synovial fluid additive in drug loading.
Preferably, the joint synovial fluid additive is loaded with anti-inflammatory drugs, and the anti-inflammatory drugs are diclofenac sodium and celecoxib.
The invention provides a method for loading an anti-inflammatory drug in the joint synovial fluid additive.
The invention also provides the cytotoxicity of the joint synovial fluid additive and the application of the joint synovial fluid additive in wear resistance and friction reduction in joint synovial fluid.
The anti-inflammatory drug can be one or a mixture of more drugs with anti-inflammatory effect.
The drug carrier of the present invention can be used for the treatment of diseases. The disease to which the drug carrier of the present invention is applied may be a disease of the joint type, and the kind of the pharmaceutically active ingredient contained in the drug carrier of the present invention may vary depending on the intended application. That is, the drug carrier of the present invention can be used in a variety of medical applications.
The invention has the following beneficial results:
(1) the COF is innovatively synthesized in a high yield by adopting a mild and simple method, and is selected as a bionic joint synovial fluid additive, so that the great friction reduction and wear resistance are realized, and the lubricating life of the joint is remarkably prolonged.
(2) The COF is composed of light elements, is used as a carrier and an additive, avoids the burden of introducing heavy metals on a body, has good photo-thermal conversion performance, and can realize the regulation and control of the temperature of joint parts.
(3) Realizes the lossless, high-volume loading and slow release of the medicine. The anti-inflammatory drug (such as diclofenac sodium, DS; celecoxib, CLX) is adsorbed on COF through hydrogen bond action and conjugation, so that the influence of covalent bonds on the activity of drug molecules is avoided, and the adsorption mode can realize the slow release of the drug and is beneficial to maintaining good treatment effect for a long time.
Drawings
FIG. 1 is a transmission electron microscope image of COF-PDA;
FIG. 2 is a graph showing photothermal data of COF-PDA and ultrapure water;
FIG. 3 is a UV spectrum of DS, COF-PDA and COF-PDA supported DS (one); (II) ultraviolet spectrograms of CLX, COF-PDA and COF-PDA supported CLX;
FIG. 4 is a graph showing the cytotoxicity study of COF and COF-PDA on cells;
FIG. 5 shows H under a load of 5N and a frequency of 1 Hz 2 Graph of reciprocal friction for O, and COF-PDA;
FIG. 6 is the average coefficient of friction of COF-PDA at different concentrations under the condition of 1 Hz 1N;
FIG. 7 shows the change of the friction coefficient of 7 mg/mL COF-PDA under the load of 0.5, 1, 2, 5N at the frequency of 1 Hz.
Detailed Description
In order to better understand the essence of the present invention, the following further explains the technical scheme of the present invention by specific examples.
1. Preparation of lubricants
Example 1
(1) Preparation of specific covalent organic framework materials: adding 100 mg of 3, 6-bis (5-aldehyde thiophene-2-yl) -2, 5-bis (2-ethylhexyl) pyrrolo [3,4-c ] pyrrole-1, 4 (2H, 5H) -diketone monomer into a beaker, and then adding 150 mL of chloroform for dissolving to obtain a red-purple solution A; 50 mg of tris (4-aminophenyl) amine monomer was added to a beaker and then dissolved with 150 mL of methanol to give a solution B as a light brown color. And uniformly mixing the solution A and the solution B, dropwise adding 15 mL of glacial acetic acid serving as a catalyst after stirring, and standing at room temperature for reaction for 48 hours. Centrifuging after 48 hours to remove supernatant fluid to obtain blue-green precipitate, washing the precipitate with tetrahydrofuran, and centrifuging until the supernatant fluid becomes colorless to obtain a product COF;
(2) modification of specific covalent organic framework materials: and ultrasonically dispersing the product of 1 mg in 1mL of ultrapure water, adding 0.3 mg of dopamine, adjusting the pH of the mixed solution to 8.5, and uniformly stirring for 24 hours in a dark place to obtain the COF-PDA lubricant of 1 mg/mL.
Example 2
(1) Preparation of specific covalent organic framework materials: adding 100 mg of 3, 6-bis (5-aldehyde thiophene-2-yl) -2, 5-bis (2-ethylhexyl) pyrrolo [3,4-c ] pyrrole-1, 4 (2H, 5H) -diketone monomer into a beaker, and then adding 150 mL of chloroform for dissolving to obtain a red-purple solution A; 50 mg of tris (4-aminophenyl) amine monomer was added to a beaker and then dissolved with 150 mL of methanol to give a solution B as a light brown color. And uniformly mixing the solution A and the solution B, dropwise adding 15 mL of glacial acetic acid serving as a catalyst after stirring, and standing at room temperature for reaction for 48 hours. Centrifuging after 48 h to remove the supernatant to obtain a blue-green precipitate, cleaning the precipitate with tetrahydrofuran, and centrifuging until the supernatant becomes colorless to obtain a product COF;
(2) modification of specific covalent organic framework materials: and ultrasonically dispersing the 2 mg product in 1mL of ultrapure water, adding 0.5 mg of dopamine, adjusting the pH of the mixed solution to 8.5, and uniformly stirring for 24 hours in a dark place to obtain a 2 mg/mL COF-PDA lubricant.
Example 3
(1) Preparation of specific covalent organic framework materials: adding 100 mg of 3, 6-bis (5-aldehyde thiophene-2-yl) -2, 5-bis (2-ethylhexyl) pyrrolo [3,4-c ] pyrrole-1, 4 (2H, 5H) -diketone monomer into a beaker, and then adding 150 mL of chloroform for dissolving to obtain a red-purple solution A; 50 mg of tris (4-aminophenyl) amine monomer was added to a beaker and then dissolved with 150 mL of methanol to give a solution B as a light brown color. And uniformly mixing the solution A and the solution B, dropwise adding 15 mL of glacial acetic acid serving as a catalyst after stirring, and standing at room temperature for reaction for 48 hours. Centrifuging after 48 hours to remove supernatant fluid to obtain blue-green precipitate, washing the precipitate with tetrahydrofuran, and centrifuging until the supernatant fluid becomes colorless to obtain a product COF;
(2) modification of specific covalent organic framework materials: ultrasonically dispersing the 5 mg product in 1mL of ultrapure water, adding 1 mg of dopamine, adjusting the pH of the mixed solution to 8.5, and stirring at a constant speed for 24 hours in a dark place to obtain a 5 mg/mL COF-PDA lubricant.
Example 4
(1) Preparation of specific covalent organic framework materials: adding 100 mg of 3, 6-bis (5-aldehyde thiophene-2-yl) -2, 5-bis (2-ethylhexyl) pyrrolo [3,4-c ] pyrrole-1, 4 (2H, 5H) -diketone monomer into a beaker, and then adding 150 mL of chloroform for dissolving to obtain a red-purple solution A; 50 mg of tris (4-aminophenyl) amine monomer was added to a beaker and then dissolved with 150 mL of methanol to give a solution B as a light brown color. And uniformly mixing the solution A and the solution B, dropwise adding 15 mL of glacial acetic acid serving as a catalyst after stirring, and standing at room temperature for reaction for 48 hours. Centrifuging after 48 hours to remove supernatant fluid to obtain blue-green precipitate, washing the precipitate with tetrahydrofuran, and centrifuging until the supernatant fluid becomes colorless to obtain a product COF;
(2) modification of specific covalent organic framework materials: ultrasonically dispersing the 7 mg product in 1mL of ultrapure water, adding 2 mg of dopamine, adjusting the pH of the mixed solution to 8.5, and stirring at a constant speed for 24 hours in a dark place to obtain a 7 mg/mL COF-PDA lubricant.
Example 5
(1) Preparation of specific covalent organic framework materials: adding 100 mg of 3, 6-bis (5-aldehyde thiophene-2-yl) -2, 5-bis (2-ethylhexyl) pyrrolo [3,4-c ] pyrrole-1, 4 (2H, 5H) -diketone monomer into a beaker, and then adding 150 mL of chloroform for dissolving to obtain a red-purple solution A; 50 mg of tris (4-aminophenyl) amine monomer was added to a beaker and then dissolved with 150 mL of methanol to give a solution B as a light brown color. And uniformly mixing the solution A and the solution B, dropwise adding 15 mL of glacial acetic acid serving as a catalyst after stirring, and standing at room temperature for reaction for 48 hours. Centrifuging after 48 hours to remove supernatant fluid to obtain blue-green precipitate, washing the precipitate with tetrahydrofuran, and centrifuging until the supernatant fluid becomes colorless to obtain a product COF;
(2) modification of specific covalent organic framework materials: and ultrasonically dispersing the 10 mg product in 1mL of ultrapure water, adding 5 mg of dopamine, adjusting the pH of the mixed solution to 8.5, and stirring for 24 hours at a constant speed in a dark place to obtain 10 mg/mL of COF-PDA lubricant.
2. The COF-PDA prepared in the example was subjected to experiments of diclofenac sodium loading and celecoxib loading.
(1) Accurately preparing 3 mL COF-PDA solution (1, 2,5 and 7 mg/mL) in sequence, carrying out ultrasonic treatment for 20 min, adding 3 mg DS, continuing ultrasonic treatment until the solution is completely dissolved, stirring in the dark for 24 h, carrying out high-speed centrifugation on the obtained mixture, separating supernatant, washing lower solids with ultrapure water, and carrying out vacuum freeze drying to obtain solid powder.
(2) Accurately preparing 3 mL of COF-PDA solution (1, 2,5 and 7 mg/mL) in sequence, carrying out ultrasonic treatment for 20 min, adding 3 mg of CLX, continuing ultrasonic treatment until the solution is completely dissolved, stirring in the dark for 24 h, centrifuging the obtained mixture at a high speed, separating supernatant, washing lower solids with ultrapure water, and then carrying out vacuum freeze drying to obtain solid powder.
The prepared COF-PDA was subjected to transmission electron microscopy scanning, as shown in FIG. 1. The composite carrier can be seen to be spherical, and the particle size is 80-150 nm.
The photothermal data of COF-PDA under near infrared light is shown in FIG. 2. Experiments prove that the COF-PDA can quickly rise to 60 ℃ at the concentration of 0.6 mg/mL, but the temperature of the ultrapure water hardly changes under the same conditions. Therefore, the COF-PDA has good photo-thermal performance.
The UV spectrums of DS, COF-PDA and COF-PDA after loading DS are shown in FIG. 3 (one), and the data show that COF-PDA has characteristic peaks at 226 nm and 716 nm, and DS has characteristic peaks at 226 nm and 276 nm. These characteristic peaks were both detected on the UV curve of COF-PDA + DS, thus demonstrating successful loading of DS. As shown in figure 3 (II), CLX has characteristic peaks at 226 nm and 251 nm, and the characteristic peaks of the drug and the carrier are detected on the ultraviolet curve of COF-PDA + CLX, thus confirming the successful loading of the drug.
The chart of the biological toxicity study of COF and COF-PDA on cells is shown in FIG. 4. The COF and COF-PDA samples with different concentrations are cultured with cells, and experiments prove that the cell survival rate is over 90 percent. Therefore, the compound has good biocompatibility as a joint synovial fluid additive.
The tribological performance of the material as a joint synovial fluid additive is evaluated by a CFT-I type material surface performance comprehensive tester by adopting a zirconia ball and a zirconia plate as a friction pair. Under the condition of load of 5N and frequency of 1 Hz, H 2 The graph of the reciprocal friction curves of O and COF-PDA is shown in FIG. 5. The friction coefficient of pure water is about 0.6, the friction coefficient of COF-PDA is about 0.13, and the low friction coefficient can be kept unchanged for a long time, and the lubricating performance is good. In FIG. 6, the effect of COF-PDA (1, 2,5, 7, 10 mg/mL) at different concentrations under the same friction condition (1N, 1 Hz) on the friction coefficient is studied, and the result shows that COF-PDA can play a better lubricating and friction reducing effect at a concentration of 7 mg/mL. In FIG. 7, the change of the friction coefficient of 7 mg/mL COF-PDA under the load of 0.5, 1, 2, 5N at the frequency of 1 Hz was investigated. The lubricating performance of COF-PDA was tested in detail by changing the load, and the results showed that the lubricating performance was differentUnder load, the COF-PDA has a friction coefficient far lower than that of pure water, and shows good friction-reducing and wear-resisting effects. The results show that the joint synovial fluid additive has good lubricating effect and practical application value.
Claims (9)
1. A multifunctional joint synovial fluid additive is characterized in that a 3, 6-bis (5-aldehyde thiophene-2-yl) -2, 5-bis (2-ethylhexyl) pyrrolo [3,4-c ] pyrrole-1, 4 (2H, 5H) -diketone monomer and a tri (4-aminophenyl) amine monomer react to obtain a covalent organic framework material, the covalent organic framework material is modified by dopamine to load arthritis treatment drugs, and the covalent organic framework nano drug carrier joint synovial fluid additive is obtained;
the structural formula of the covalent organic framework material is as follows:
2. a method for preparing the multifunctional joint synovial fluid additive of claim 1, comprising the following steps:
(1) preparation of specific covalent organic framework materials: adding a 3, 6-bis (5-aldehyde thiophene-2-yl) -2, 5-bis (2-ethylhexyl) pyrrolo [3,4-c ] pyrrole-1, 4 (2H, 5H) -diketone monomer into a beaker, and then adding chloroform for dissolving to obtain a reddish purple solution A; adding a tri (4-aminophenyl) amine monomer into a beaker, and then dissolving with methanol to obtain a solution B with light brown color; uniformly mixing the solution A and the solution B, stirring, dropwise adding glacial acetic acid serving as a catalyst, and reacting for 48 hours at room temperature; centrifuging after 48 h to remove supernatant to obtain blue-green precipitate, washing the precipitate with tetrahydrofuran, and centrifuging until the supernatant becomes colorless; obtaining a product COF;
(2) modification of specific covalent organic framework materials: ultrasonically dispersing the COF product into ultrapure water, adding dopamine, adjusting the pH value of the mixed solution, and stirring at a constant speed in the dark; centrifuging the mixed solution to remove the supernatant, repeatedly centrifuging for 3 times by using ultrapure water, and carrying out vacuum freeze drying to obtain the modified covalent organic framework COF-PDA;
(3) and loading the medicine for treating arthritis on COF-PDA to obtain the compound joint synovial fluid additive.
3. The preparation method according to claim 2, wherein the mass ratio of 3, 6-bis (5-formylthiophen-2-yl) -2, 5-bis (2-ethylhexyl) pyrrolo [3,4-c ] pyrrole-1, 4 (2H, 5H) -dione to chloroform in step (1) is: 2:1, the mass volume of glacial acetic acid and tris (4-aminophenyl) amine is 15 ml: 50 mg.
4. The production method according to claim 2,
the rotating speed of the centrifugation in the step (1) is 5000-8000 r/min, and the time is 5-20 min;
in the step (2), the dosage of dopamine added in every 100 mg of COF is 20-50 mg;
in the step (2), the pH value of the mixed solution is 8.5.
5. The method according to claim 2, wherein the covalent organic framework is spherical with a size of 80 to 150 nm.
6. Use of a lubricity additive prepared by the process of any one of claims 2 to 5 in drug loading.
7. The use of claim 6, wherein the medicament is an anti-inflammatory medicament.
8. The use of claim 7, wherein the anti-inflammatory agent is diclofenac sodium and celecoxib.
9. Use of a lubricious additive prepared by the process of any of claims 2-5 in the preparation of a joint synovial drug.
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