CN116102869A - Dual-stimulus-responsive organosilicon-based hydrogel material, and preparation method and application thereof - Google Patents
Dual-stimulus-responsive organosilicon-based hydrogel material, and preparation method and application thereof Download PDFInfo
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- CN116102869A CN116102869A CN202310019784.1A CN202310019784A CN116102869A CN 116102869 A CN116102869 A CN 116102869A CN 202310019784 A CN202310019784 A CN 202310019784A CN 116102869 A CN116102869 A CN 116102869A
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/06—Ointments; Bases therefor; Other semi-solid forms, e.g. creams, sticks, gels
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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
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7028—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages
- A61K31/7034—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages attached to a carbocyclic compound, e.g. phloridzin
- A61K31/704—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages attached to a carbocyclic compound, e.g. phloridzin attached to a condensed carbocyclic ring system, e.g. sennosides, thiocolchicosides, escin, daunorubicin
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K41/00—Medicinal preparations obtained by treating materials with wave energy or particle radiation ; Therapies using these preparations
- A61K41/0042—Photocleavage of drugs in vivo, e.g. cleavage of photolabile linkers in vivo by UV radiation for releasing the pharmacologically-active agent from the administered agent; photothrombosis or photoocclusion
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- A—HUMAN NECESSITIES
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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
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/24—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing atoms other than carbon, hydrogen, oxygen, halogen, nitrogen or sulfur, e.g. cyclomethicone or phospholipids
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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
- C08G65/00—Macromolecular compounds obtained by reactions forming an ether link in the main chain of the macromolecule
- C08G65/02—Macromolecular compounds obtained by reactions forming an ether link in the main chain of the macromolecule from cyclic ethers by opening of the heterocyclic ring
- C08G65/32—Polymers modified by chemical after-treatment
- C08G65/329—Polymers modified by chemical after-treatment with organic compounds
- C08G65/336—Polymers modified by chemical after-treatment with organic compounds containing silicon
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- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08J—WORKING-UP; GENERAL PROCESSES OF COMPOUNDING; AFTER-TREATMENT NOT COVERED BY SUBCLASSES C08B, C08C, C08F, C08G or C08H
- C08J3/00—Processes of treating or compounding macromolecular substances
- C08J3/02—Making solutions, dispersions, lattices or gels by other methods than by solution, emulsion or suspension polymerisation techniques
- C08J3/03—Making solutions, dispersions, lattices or gels by other methods than by solution, emulsion or suspension polymerisation techniques in aqueous media
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- C—CHEMISTRY; METALLURGY
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- C08J—WORKING-UP; GENERAL PROCESSES OF COMPOUNDING; AFTER-TREATMENT NOT COVERED BY SUBCLASSES C08B, C08C, C08F, C08G or C08H
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Abstract
The invention provides a dual-stimulus-responsive organosilicon-based hydrogel material, and a preparation method and application thereof. The invention takes bridging organosilane with photoresponsive property and silane modified polyethylene glycol or silane modified polyethylene glycol-co-propylene glycol copolymer as raw materials, and is prepared by hydrolysis polycondensation reaction. The organosilicon-based hydrogel provided by the invention has molecular chain segment fracture under 365nm light irradiation, and has light-controlled drug molecular release behavior; the pH stimulation response is also provided, and the medicine can be released in a timing and positioning way. The organosilicon-based hydrogel effectively prolongs the residence time of the medicine, improves the capability of continuously releasing the medicine, and has important application value in the field of targeted release of target molecules and medicine slow release.
Description
Technical Field
The invention relates to a dual-stimulus-responsive organosilicon-based hydrogel material, and a preparation method and application thereof, and belongs to the technical field of new materials.
Background
The drug controlled release carrier material has important application in the field of disease treatment, but the material has certain drug burst release behavior when releasing drugs. The aims of prolonging the residence time of the medicine, reducing the administration times and reducing the toxicity of the medicine are also development in the technical field of medicine controlled release. The hydrogel is a polymer material with a cross-linked network structure, and has wide application prospect in the fields of tissue engineering, drug slow release and the like. Currently, drug release rates are controlled by increasing the degree of cross-linking of hydrogels by forming covalent chemical bonds or strong physical interactions between the drug and the hydrogel matrix to address the abrupt release behavior of the drug. The strategy can solve the problem of drug burst release and control the drug release rate to a certain extent, but has the defect of influencing the drug activity and the hydrogel body structure. The intelligent drug controlled release system can accurately control the drug release, can effectively solve the problem of drug burst release behavior and control the drug release rate, and enhances the slow release effect. Patent CN108976758A discloses a photosensitive polyethylene glycol-based antibacterial hydrogel dressing and a preparation method thereof, and the material provides the antibacterial effect of the hydrogel by utilizing a method of releasing antibiotics by light control; wherein, the antibiotic molecule is covalently connected with the hydrogel matrix polymer, which has the defect of affecting the drug activity and the hydrogel body structure. Patent CN111234238A discloses a silicone polyethylene glycol hydrogel material with self-healing properties and a preparation method thereof, which cannot respond to the stimulus condition of the external environment.
The organic silicon material has good biocompatibility and physiological inertia, so that the hydrogel containing the organic silicon structural unit has important application prospect in the fields of drug release, tissue engineering, silicon hydrogel lenses and the like. The silicon-containing hydrogel materials currently reported are not responsive, particularly photo-responsive, to external stimuli. The single condition response stimulation material often has limitations in application fields such as targeted release of target molecules, drug controlled release and the like, and the double stimulus response hydrogel has better application potential in the field of biomedical materials, in particular to light and pH response hydrogel. Therefore, developing an organosilicon-based hydrogel material with biocompatibility and multiple responsivity can effectively prolong the residence time of the drug and release the drug in a timing and positioning way, and has important significance in the fields of targeted therapy, drug controlled release, tissue engineering and other human biomedical fields.
Disclosure of Invention
Aiming at the defects existing in the prior art, the invention provides a dual-stimulus-responsive organosilicon-based hydrogel material, and a preparation method and application thereof. The invention takes bridging organosilane with photoresponsive property and silane modified polyethylene glycol or silane modified polyethylene glycol-co-propylene glycol copolymer as raw materials, and is prepared by hydrolysis polycondensation reaction. The organosilicon-based hydrogel provided by the invention has molecular chain segment fracture under 365nm light irradiation, and has light-controlled drug molecular release behavior; the pH stimulation response is also provided, and the medicine can be released in a timing and positioning way. The organosilicon-based hydrogel effectively prolongs the residence time of the medicine, improves the capability of continuously releasing the medicine, and has important application value in the field of targeted release of target molecules and medicine slow release.
The technical scheme of the invention is as follows:
a dual stimulus responsive silicone-based hydrogel material, the silicone-based hydrogel material being a polymer having a crosslinked network structure; the organosilicon-based hydrogel material is prepared by hydrolysis polycondensation reaction of photo-responsive bridged silane and silane modified polyether;
the photo-responsive bridged silane has the structural formula: x (SiR) 1 R 2 R 3 ) 2 ；
Wherein R is 1 And R is 2 Each independently selected from one of methoxy or ethoxy, R 3 One selected from methyl, ethyl, phenyl, methoxy or ethoxy; x has the structure shown below:
the silane modified polyether is silane modified polyethylene glycol or silane modified polyethylene glycol-co-propylene glycol copolymer.
According to the present invention, the silane-modified polyethylene glycol-co-propylene glycol copolymer has the structure shown below:
(R 4 R 5 R 6 )Si(CH 2 ) 3 NHOCOCH 2 CH 2 O(CH 2 CH 2 O) m (CH 2 CH(CH 3 )O) n CH 2 CH(CH 3 )OCONH(CH 2 ) 3 Si(R 4 R 5 R 6 )，
(R 4 R 5 R 6 )Si(CH 2 ) 3 NHOCNHCH 2 CH 2 O(CH 2 CH 2 O) m (CH 2 CH(CH 3 )O) n CH 2 CH(CH 3 )NHCONH(CH 2 ) 3 Si(R 4 R 5 R 6 )，
or alternatively, the first and second heat exchangers may be,
(R 4 R 5 R 6 )Si(CH 2 ) j O(CH 2 CH 2 O) m (CH 2 CH(CH 3 )O) n (CH 2 ) j Si(R 4 R 5 R 6 )；
wherein R is 4 ，R 5 Each independently selected from one of methoxy or ethoxy, R 6 One selected from methyl, ethyl, phenyl, methoxy or ethoxy; m=1-180; n=1-135; j=3 or 5.
According to a preferred embodiment of the invention, the silane-modified polyethylene glycol has the structure shown below:
(R 4 R 5 R 6 )Si(CH 2 ) 3 NHOCOCH 2 CH 2 O(CH 2 CH 2 O) m CH 2 CH 2 OCONH(CH 2 ) 3 Si(R 4 R 5 R 6 )
wherein R is 4 ，R 5 Each independently selected from one of methoxy or ethoxy, R 6 One selected from methyl, ethyl, phenyl, methoxy or ethoxy; preferably, R 6 Selected from methyl; wherein m=45-90.
According to a preferred embodiment of the invention, the bridge is light-responsiveIn the structural formula of the disilane, R 1 And R is 2 Each independently selected from one of methoxy or ethoxy, R 3 Selected from methyl groups.
The preparation method of the dual-stimulus responsive organosilicon-based hydrogel material comprises the following steps:
(1) Polyether and reactive organosilane S in solvent A 1 Obtaining silane modified polyether through reaction; the polyether is polyethylene glycol or polyethylene glycol-co-propylene glycol copolymer;
(2) In a solvent B, in the presence of alkali, oxidizing the compound of the formula I by potassium permanganate to obtain a compound of the formula II; in a solvent C, in the presence of borane, carrying out reduction reaction on the compound of the formula II to obtain a compound of the formula III; in a solvent D, under the action of triethylamine, reacting the compound shown in the formula III with chloroacetyl chloride to obtain a compound shown in the formula IV; in solvent E, under the action of triethylamine, a compound of formula IV and an active silane S 2 Obtaining photo-responsive bridging silane through reaction;
(3) Dissolving silane modified polyether in water, performing hydrolysis reaction, and then adjusting the pH value to be acidic; and dropwise adding an ethanol solution of photo-responsive bridging silane, and reacting until gel is formed, thus obtaining the dual-stimulus responsive organosilicon-based hydrogel material.
According to a preferred embodiment of the present invention, in step (1), solvent A is tetrahydrofuran or acetonitrile; the volume ratio of the mass of the polyether to the solvent A is 1:1-8.
According to the invention, in the step (1), the polyethylene glycol-co-propylene glycol copolymer has a number average molecular weight of 1000 to 8000g/mol; has the following structure:
HOCH 2 CH 2 O(CH 2 CH 2 O) m (CH 2 CH(CH 3 )O) n CH 2 CH(CH 3 )OH；
NH 2 CH 2 CH 2 O(CH 2 CH 2 O) m (CH 2 CH(CH 3 )O) n CH 2 CH(CH 3 )NH 2 ；
CH 2 ＝CHCH 2 CH 2 CH 2 O(CH 2 CH 2 O) m (CH 2 CH(CH 3 )O) n CH 2 CH 2 CH 2 CH＝CH 2 ；
or, CH 2 ＝CHCH 2 O(CH 2 CH 2 O) m (CH 2 CH(CH 3 )O) n CH 2 CH＝CH 2 ；
Wherein m=1-180; n=1-135.
According to the invention, in the step (1), the polyethylene glycol has a number average molecular weight of 2000 to 4000g/mol; has the following structure: HOCH 2 CH 2 O(CH 2 CH 2 O) m CH 2 CH 2 OH; wherein m=45-90.
According to a preferred embodiment of the invention, in step (1), the reactive organosilane S 1 Is isocyanate propyl triethoxy silane, isocyanate propyl trimethoxy silane, isocyanate propyl methyl dimethoxy silane, isocyanate propyl methyl diethoxy silane, siH (R) 4 R 5 R 6 ) (hydrosilane) or Cl (CH) 2 ) 3 Si(R 4 R 5 R 6 ) (chlorohydrocarbyl silane); preference is given to isocyanatopropyltriethoxysilane, isocyanatopropylmethyldimethoxysilane, isocyanatopropyltrimethoxysilane or isocyanatopropylmethyldiethoxysilane.
According to a preferred embodiment of the invention, in step (1), the polyether and the reactive organosilane S 1 The molar ratio of (2) is 1:2-2.5.
According to the invention, in step (1), the reaction temperature is 40-80 ℃, the reaction time is 2-6h, and the reaction is carried out under stirring. Preferably, the reaction temperature is 60 to 70 ℃.
According to a preferred embodiment of the invention, in step (1), the reactive organosilane S 1 Is added into a system containing polyether in a dropwise manner; the dropwise addition was carried out under stirring.
According to a preferred embodiment of the invention, in step (1), the polyether is dried under reduced pressure and then reacted with the reactive organosilane S 1 And (3) reacting.
According to a preferred embodiment of the present invention, in step (2), solvent B is water; the mass ratio of the compound of the formula I to the solvent B is 5-10g/L; the mass ratio of the compound of the formula I to the alkali is 1:0.4-0.5; the mass ratio of the compound of the formula I to the potassium permanganate is 1:4-5; the oxidation reaction temperature is 80-100 ℃ and the oxidation reaction time is 40-50h.
According to a preferred embodiment of the present invention, in step (2), solvent C is tetrahydrofuran; the mass ratio of the compound of the formula II to the solvent C is 0.01-0.5g/mL; the mass ratio of the borane to the compound of the formula II is 0.1-1:1, a step of; the reduction reaction temperature is room temperature, and the reduction reaction time is 40-60 h; the borane is added dropwise to the reaction system containing the compound of formula II and solvent C.
According to a preferred embodiment of the present invention, in step (2), solvent D is acetonitrile; the mass ratio of the compound of the formula III to the solvent D is 0.02-0.05g/mL; the mass ratio of the triethylamine to the compound of the formula III is 1-1.5:1; the mass ratio of the compound of the formula III to the chloroacetyl chloride is 1:1.1-1.5; the reaction temperature is 60-70 ℃ and the reaction time is 3-8h.
According to a preferred embodiment of the present invention, in step (2), solvent E is acetonitrile; the volume ratio of the mass of the compound of the formula IV to the solvent E is 0.01-0.1g/mL; the mass ratio of the triethylamine to the compound of the formula IV is 0.5-1.2:1; compounds of formula IV and reactive silanes S 2 The molar ratio of (2) is 1:2-2.5; the reaction temperature is 60-80 ℃ and the reaction time is 4-8h.
According to a preferred embodiment of the invention, in step (2), the reactive silane S 2 Is NH 2 (CH 2 ) 3 Si(R 1 R 2 R 3 )，R 1 And R is 2 Each independently selected from one of methoxy or ethoxy, R 3 One selected from methyl, ethyl, phenyl, methoxy or ethoxy; preferably aminopropyl methyldimethoxy silane or aminopropyl methyldiethoxy silane.
According to the invention, in the step (3), the mass ratio of the silane-modified polyether to the water is preferably 0.1-9:1, and more preferably 0.3-3:1; the hydrolysis reaction temperature is 30-90 ℃, preferably 60-70 ℃; the hydrolysis reaction time is 20-50min.
According to the present invention, in the step (3), the pH is adjusted to 2 to 3 using an aqueous hydrochloric acid solution having a mass concentration of 0.05 to 1 mol/L.
According to a preferred embodiment of the invention, in step (3), the concentration of the ethanol solution of the photo-responsive bridging silane is between 0.1 and 1g/mL.
According to a preferred embodiment of the invention, in step (3), the mass ratio of silane-modified polyether to photo-responsive bridging silane is 1-9:1, preferably 1-4:1.
According to a preferred embodiment of the invention, in step (3), the dropping rate of the photo-responsive bridging silane is from 0.01 to 0.1 ml/min.
According to a preferred embodiment of the invention, in step (3), after the addition of the photo-responsive bridging silane, the reaction temperature is 30 to 90 ℃, preferably 60 to 70 ℃.
According to the invention, in the step (3), the reaction temperature, the pH in the system and the charging mode of the photo-responsive bridging silane have important influences on the preparation and the performance of the organosilicon-based hydrogel. The reaction temperature is too high or too low, which is not beneficial to control of the reaction process; the proper pH value in the system has important influence on the control of the silane hydrolytic polycondensation process, and too high or too low pH value leads to poor control of the silane hydrolytic polycondensation process and has adverse influence on the gel performance; the compatibility of the photo-responsive bridged silane with the system, the dropping rate and the addition of ethanol play an important role in controlling the hydrolytic condensation process of the silane.
The application of the dual-stimulus-responsive organosilicon-based hydrogel material is used as a carrier for loading drug molecules to obtain the dual-stimulus-responsive drug-loaded organosilicon-based hydrogel material so as to realize drug slow release and drug targeted release.
According to a preferred embodiment of the invention, the application method comprises the steps of:
(1) The preparation method of the silane modified polyether is as described above;
(2) The preparation method of the photo-responsive bridging silane is as described above;
(3) Dissolving silane modified polyether in water, adding a drug, fully mixing and dispersing uniformly, carrying out hydrolysis reaction, and then regulating the pH value to be acidic; and dropwise adding an ethanol solution of photo-responsive bridging silane, and reacting until gel is formed, thus obtaining the dual-stimulus responsive drug-loaded organosilicon-based hydrogel material.
Preferably, the drug is doxorubicin, paclitaxel, tetracycline, epirubicin, etimicin or pirarubicin; the mass ratio of the medicine to the silane modified polyether is 0.0001-1:1.
According to the invention, in the application method, other preparation methods and conditions are consistent with those of the dual-stimulus-responsive organosilicon-based hydrogel material.
The reaction route of the photo-responsive bridging silane of the invention is as follows:
wherein R is 1 And R is 2 Each independently selected from one of methoxy or ethoxy, R 3 Selected from one of methyl, ethyl, phenyl, methoxy or ethoxy.
The invention has the technical characteristics and beneficial effects that:
1. the invention discloses an organosilicon-based hydrogel material with dual stimulus response of light and pH, which is prepared by hydrolysis polycondensation of bridged silane with light response and silane modified polyether. The organic silicon-based hydrogel contains a photosensitive chain segment, when the organic silicon-based hydrogel is illuminated, the photosensitive chain segment is subjected to photoinduced fracture, and the organic silicon-based hydrogel polymer structure generates degradation behavior; organosilicon-based hydrogels have Si-O-Si mer at H + 、OH - And the aqueous phase environment of the isoelectric medium is degradable. The hydrogel has controllable light and pH degradation capability.
2. The organosilicon-based hydrogel provided by the invention has molecular chain segment fracture under 365nm light irradiation, and has light-controlled drug molecular release behavior; the pH stimulation response is also provided, and the medicine can be released in a timing and positioning way. The organosilicon-based hydrogel material prepared by the invention has good drug controlled release capability, does not generate drug burst release, can effectively prolong the residence time of the drug, improves the capability of continuously releasing the drug, and has important application value in the fields of targeted release of target molecules and drug release. The structure of silicone-based hydrogels has an important impact on the stimuli-responsiveness of the material and the ability to release drugs. Only the silicone-based hydrogels of the specific structure of the present invention achieve the excellent effects of the present invention. After the organosilicon-based hydrogel is used for loading the medicine, the medicine is continuously released in an environment simulating gastric juice (pH=1), and the medicine can be completely released for 11 days; the organosilicon-based hydrogel has the function of releasing medicines in a timing and quantitative manner under the light-control condition.
3. The organosilicon-based hydrogel material prepared by the invention adopts an in-situ medicine encapsulation method, has no covalent bond effect with a target medicine, does not damage the structure and activity of the medicine, and also does not damage the organosilicon-based hydrogel structure.
4. The organosilicon-based hydrogel prepared by the invention has adjustable and good mechanical properties, and the compressive strength can reach 0.65MPa. The organosilicon-based hydrogel has a three-dimensional network structure, and the mechanical properties of the organosilicon-based hydrogel can be effectively regulated by regulating the molecular structure and the functionality of the silane-modified polyether polymer, the functionality of the bridging silane and the molar ratio of the two materials.
5. The preparation method of the organosilicon-based hydrogel material with dual stimulus response of light and pH is simple, the reaction condition is mild, and the organosilicon-based hydrogel material can be prepared through silane hydrolysis and polycondensation, and is environment-friendly.
Drawings
FIG. 1 is an infrared spectrum of a dual stimulus-responsive silicone-based hydrogel material prepared in example 4;
fig. 2 is a graph showing the light-controlled drug release behavior of the drug-loaded silicone-based hydrogels prepared in application examples 2 and 4.
Detailed Description
The invention will be further illustrated with reference to specific examples, but is not limited thereto. All techniques implemented based on the above description of the invention are intended to be included within the scope of the invention.
The experimental methods described in the examples below, if not specified, are all conventional methods, and the reagents and materials, if not specified, are all commercially available.
Example 1
A method for preparing a dual stimulus responsive silicone-based hydrogel material, comprising the steps of:
(1) Reducing pressure to remove water from polyethylene glycol with the number average molecular weight of 2000 at 70 ℃, and then restoring to room temperature; 10.0g of dried polyethylene glycol was dissolved in 57mL of tetrahydrofuran; 2.50g of isocyanate propyl triethoxysilane is added dropwise under the condition of stirring, nitrogen protection is adopted, and the mixture is stirred and reacted for 5 hours at 60 ℃ to prepare 0.220g/ml silane modified polyethylene glycol (PEG) 2000 -T 1 ) Tetrahydrofuran solution, and nitrogen filling for preservation.
(2) 700ml of water, 6.00g of a compound of formula I, 2.54g of NaOH and 25.0g of potassium permanganate are sequentially added into a 2.00L four-neck flask, the mixture is heated to 90 ℃, stirred and reacted for 48 hours, and 7.46g of white solid compound II is obtained through suction filtration, washing and acid washing, and the yield is 89.0%;
7.00g of the compound of formula II is weighed and dissolved in 25.0ml of tetrahydrofuran, 230ml of Borane (BH) tetrahydrofuran complex (1 mol/L) is gradually added under the ice bath and nitrogen protection condition, stirring is carried out at room temperature under the nitrogen protection condition for 48 hours, 35.0ml of methanol is added for treating excessive borane, stirring is carried out at room temperature for 2 hours, the solvent is removed under reduced pressure, alkaline washing and water washing are carried out for multiple times, 5.00g of anhydrous magnesium sulfate is added for drying, 4.55g of crude product of the compound of formula III is obtained, and the yield is 74.9%;
0.550g of the compound of formula III is dissolved in 15.0ml of acetonitrile, 0.608g of triethylamine and 0.679g of chloroacetyl chloride are added dropwise in sequence, the mixture is heated to 65 ℃ and stirred for reaction for 5 hours. Then, through spin steaming, water washing, drying and column chromatography technology, 0.808g of a product compound of a formula IV is obtained, and the yield is 80.0%;
dissolving 0.730g of a compound of formula IV in 15.0ml of anhydrous acetonitrile, sequentially dripping 0.440g of triethylamine and 0.830g of aminopropyl methyl diethoxy silane, heating to 65 ℃, stirring for reaction for 6 hours, filtering to remove amine salt, and removing solvent under reduced pressure to obtain 1.19g of photo-responsive bridged silane E1, wherein the yield is 85.0%;
absolute ethyl alcohol is added into 1.19g E1 as a diluent of silane monomer to obtain 0.5g/ml E1 solution, and the solution is filled with nitrogen for sealing and preservation.
(3) 4.40ml of PEG at 0.220g/ml 2000 -T 1 The solvent was removed from the tetrahydrofuran solution under reduced pressure to give 0.968g of PEG 2000 -T 1 1.5ml of water was added to dissolve PEG 2000 -T 1 The hydrolysis was continued with stirring at 70 ℃ for 30 minutes and the pH of the system solution was adjusted to = 3 using 0.1mol/L aqueous hydrochloric acid; dropwise adding 0.5ml of E1 solution (containing 0.250g of E1) prepared in the step (2), continuously stirring at 70 ℃ for 3 hours after 20 minutes, and continuously reacting until gel is formed after reducing pressure for 30 minutes to remove part of solvent, thereby obtaining the dual-stimulus-responsive organosilicon-based hydrogel material NB-PEGT 1-1 (E1 and PEG) 2000 -T 1 The molar ratio of (2) is 1:1).
The hydrogel prepared by the embodiment has a crosslinked network structure, and the compressive strength of the hydrogel can reach 0.6MPa.
Application example 1
2.20ml of PEG prepared in step (1) of example 1, 0.220g/ml was added 2000 -T 1 The tetrahydrofuran solution was depressurized to remove the solvent to give 0.484g of PEG 2000 -T 1 Adding 0.8ml water and 0.4ml 2mg/ml Doxorubicin (DOX) aqueous solution to dissolve PEG 2000 -T 1 The hydrolysis was continued with stirring at 70 ℃ for 30 minutes and the pH of the system solution was adjusted to = 3 using 0.1mol/L aqueous hydrochloric acid; dropwise adding 0.25ml of E1 solution (containing 0.125g of E1) prepared in the step (2) of the example 1, continuously stirring at 70 ℃ for 3 hours after the dropwise addition of the solution for 10 minutes, and continuously reacting until drug-loaded gel is formed after the decompression for 30 minutes to remove part of solvent, thereby obtaining the silicone-based drug-loaded gel material DOX@NB-PEGT 1-1 。
Preparing the above gel into two equal parts, and respectively placing inIn 30ml of buffer solution with ph=7.4 (normal physiological condition) and ph=1 (simulated gastric acid environment), 3ml of buffer solution is taken out at regular intervals, and the same volume of buffer solution is timely replenished. Analysis of 3ml of DOX-containing buffer removed at the various intervals described above was performed by UV-vis, DOX@NB-PEGT 1-1 The organosilicon-based hydrogel can continuously release the medicine for 11 days under the environment simulating gastric acid, and the medicine is completely released.
Example 2
A method for preparing a dual stimulus responsive silicone-based hydrogel material, comprising the steps of:
(1) Reducing pressure to remove water from polyethylene glycol with the number average molecular weight of 2000 at 70 ℃, and then restoring to room temperature; 20.0g of dried polyethylene glycol is dissolved in 73mL of tetrahydrofuran; 3.97g of isocyanatopropyl methyl dimethoxy silane is added dropwise under stirring, and the mixture is stirred and reacted for 3 hours under the protection of nitrogen at 60 ℃ to prepare 0.330g/ml of silane modified polyethylene glycol (PEG) 2000 -S) tetrahydrofuran solution, and filling nitrogen for preservation.
(2) The preparation of the compound of formula II-the compound of formula IV is described in example 1.
1.00g of the compound of formula IV is dissolved in 30.0ml of anhydrous acetonitrile, 0.610g of triethylamine and 0.970g of aminopropyl methyldimethoxy silane are sequentially added dropwise, the mixture is heated to 70 ℃ and stirred for reaction for 6 hours, amine salts are removed through suction filtration, the solvent is removed through decompression, and 1.49g of photo-responsive bridged silane E2 is obtained, and the yield is 85.3%.
Absolute ethyl alcohol is added into 1.49g of E2 as a diluent of silane monomer to obtain 0.5g/ml E2 solution, and the solution is filled with nitrogen for sealing and preservation.
(3) 2.40ml of 0.330g/ml PEG 2000 The solvent was removed from the S tetrahydrofuran solution under reduced pressure to give 0.792g of PEG 2000 -S；1.30ml of water was added to dissolve PEG 2000 S, continuing to hydrolyze at 65 ℃ with stirring for 30 minutes, and adjusting the ph=3 of the system solution with 0.1mol/L aqueous hydrochloric acid; dropwise adding 0.40ml of E2 solution (containing 0.200g of E2) prepared in the step (2), continuously stirring at 70 ℃ for reaction for 5 hours after 20 minutes, and continuously reacting until gel is formed after reducing pressure for 30 minutes to remove part of solvent, thereby obtaining the dual-stimulus-responsive organosilicon-based hydrogel material NB-PEGS 1-1 (E2 and PEG) 2000 The molar ratio of S is 1:1).
The compressive strength of the hydrogel prepared in the embodiment can reach 0.65MPa.
Application example 2
2.40ml of PEG prepared in example 2, step (1) at 0.330g/ml 2000 The solvent was removed from the S tetrahydrofuran solution under reduced pressure to give 0.792g of PEG 2000 S, dissolving PEG by adding 1ml of water and 0.6ml of 2mg/ml of Doxorubicin (DOX) aqueous solution 2000 S, continuing to hydrolyze at 70 ℃ with stirring for 30 minutes, and adjusting the ph=3 of the system solution with 0.1mol/L aqueous hydrochloric acid; dropwise adding 0.40ml of E2 solution (containing 0.200g E2) prepared in the step (2) of the example 2, continuously stirring at 70 ℃ for 3 hours after 20 minutes, and continuously reacting until drug-loaded gel is formed after reducing pressure for 15 minutes to remove part of solvent to obtain the silicone-based drug-loaded gel material DOX@NB-PEGS 1-1 。
The medicine carrying gel is prepared into trisections, wherein two parts of medicine carrying gel are respectively placed in 30ml of buffer solution with pH=7.4 (normal physiological condition) and pH=2, 3ml of buffer solution is taken out at regular intervals, and the buffer solution with the same volume is timely supplemented. The third part of medicine carrying gel is placed in 30ml of buffer solution with pH=7.4 (normal physiological condition), illumination is respectively carried out for 10 minutes at 1, 6, 9 and 13 hours (365 nm), illumination is not applied in other time, 3ml of buffer solution is taken out at regular intervals, and buffer solution with the same volume is timely supplemented; and sampling for 1, 6, 9 and 13 hours, and resampling after illumination is finished. Analysis of 3ml of DOX-containing buffer removed at the various intervals described above was performed by UV-vis, DOX@NB-PEGS 1-1 The silicone-based hydrogels can release Doxorubicin (DOX) continuously for up to 42 hours at ph=2, and the drug is released entirely. In "on-off" mode, NB-PEGS 1-1 The silicone-based hydrogels exhibited timed and quantitative light-controlled drug release behavior as shown in fig. 2.
Example 3
A method for preparing a dual stimulus responsive silicone-based hydrogel material, comprising the steps of:
(1) Reducing pressure to remove water from polyethylene glycol with the number average molecular weight of 2000 at 70 ℃, and then restoring to room temperature; 20.0g of dried polyethylene glycol is taken and dissolved in 86mL of tetrahydrofuran; under the stirring condition, 2.30g of isocyanate propyl trimethoxy silane and nitrogen protection are added dropwise, and the mixture is stirred and reacted for 5 hours at 60 ℃ to prepare 0.260g/ml silane modified polyethylene glycol PEG 2000 -T 2 Tetrahydrofuran solution, and nitrogen filling for preservation.
(2) The preparation of the compound of formula II-the compound of formula IV is described in example 1.
1.00g of the compound of formula IV is dissolved in 30.0ml of anhydrous acetonitrile, 0.610g of triethylamine and 0.970g of aminopropyl methyldimethoxy silane are sequentially added dropwise, the mixture is heated to 65 ℃ and stirred for reaction for 6 hours, amine salts are removed through suction filtration, the solvent is removed through decompression, and 1.48g of photo-responsive bridged silane E2 is obtained, and the yield is 84.2%.
And absolute ethyl alcohol is added into 1.48g of photoresponsive E2 as a diluent of silane monomer to obtain 0.4g/ml E2 solution, and nitrogen is filled for sealing and preservation.
(3) 4.40ml of 0.260g/ml PEG 2000 -T 2 The solvent was removed from the tetrahydrofuran solution under reduced pressure to give 1.14g of PEG 2000 -T 2 The method comprises the steps of carrying out a first treatment on the surface of the 1.50ml of water was added to dissolve PEG 2000 -T 2 The hydrolysis was continued with stirring at 65 ℃ for 30 minutes and the pH of the system solution was adjusted to = 3 using 0.1mol/L aqueous hydrochloric acid; dropwise adding 1.35ml of E2 solution (containing 0.54g E2) prepared in the step (2), continuously stirring at 70 ℃ for reaction for 6 hours after 20 minutes, removing part of solvent under reduced pressure, and continuously reacting until gel is formed to obtain the dual-stimulus-responsive organosilicon hydrogel material NB-PEGT 2-1 (E2 and PEG) 2000 -T 2 The molar ratio of (2:1).
The compressive strength of the hydrogel prepared by the embodiment can reach 0.45MPa.
Application example 3
2.20ml of PEG prepared in example 3, step (1) at 0.260g/ml 2000 -T 2 The solvent was removed from the tetrahydrofuran solution under reduced pressure to give 0.572g of PEG 2000 -T 2 Adding 0.8ml water and 0.4ml 2mg/ml Doxorubicin (DOX) aqueous solution to dissolve PEG 2000 -T 2 The hydrolysis was continued with stirring at 70 ℃ for 30 minutes and the pH of the system solution was adjusted to = 3 using 0.1mol/L aqueous hydrochloric acid; dropwise adding 0.67ml of E2 solution prepared in the step (2) in the example 3 (containing 0.268g of E2), continuously stirring at 70 ℃ for 3 hours after the completion of the dropwise addition, and continuously reacting until drug-loaded gel is formed after reducing pressure for 30 minutes to remove part of solvent, thereby obtaining the silicone-based drug-loaded gel material DOX@NB-PEGT 2-1 。
The drug-loaded gel is prepared into two equal parts, and is respectively placed in 30ml of buffer solution with pH=7.4 (normal physiological condition) and pH=1, 3ml of buffer solution is taken out at regular intervals, and the buffer solution with the same volume is timely replenished. Analysis of 3ml of DOX-containing buffer removed at the various intervals described above was performed by UV-vis, DOX@NB-PEGT 1-1 The silicone-based hydrogel can release doxorubicin continuously for 8 days under simulated gastric acid environment (ph=1), and the drug is released completely.
Example 4
A method for preparing a dual stimulus responsive silicone-based hydrogel material, comprising the steps of:
(1) Removing water from polyethylene glycol with the number average molecular weight of 2000 in a vacuum drying oven at 115 ℃ for 24 hours, and then restoring to room temperature; 20.0g of dried polyethylene glycol is taken and dissolved in 74mL of tetrahydrofuran; under the stirring condition, 2.87g of isocyanate propyl methyl diethoxy silane and nitrogen protection are added dropwise, and the mixture is stirred and reacted for 4 hours at 60 ℃ to prepare 0.310g/ml silane modified polyethylene glycol PEG 2000 -S 1 Tetrahydrofuran solution, and nitrogen filling for preservation.
(2) The preparation of the compound of formula II-the compound of formula IV is described in example 1.
0.730g of the compound of formula IV is taken and dissolved in 15.0ml of anhydrous acetonitrile, 0.440g of triethylamine and 0.830g of aminopropyl methyldiethoxysilane are added dropwise in turn, the mixture is heated to 65 ℃ and stirred for reaction for 6 hours, the amine salt is removed by suction filtration, the solvent is removed by decompression, and 1.18g of photo-responsive bridged silane E1 is obtained, and the yield is 83.9%.
Absolute ethyl alcohol is added into 1.18g of E1 as a diluent of silane monomer to obtain 0.5g/ml E1 solution, and the solution is filled with nitrogen for sealing and preservation.
(3) 2.40ml of 0.310g/ml PEG 2000 -S 1 The solvent was removed from the tetrahydrofuran solution under reduced pressure to give 0.744g of PEG 2000 -S 1 The method comprises the steps of carrying out a first treatment on the surface of the 1.20ml of water was added to dissolve PEG 2000 -S 1 Stirring at 70 ℃ for 30 minutes, and adjusting the system solution ph=3 using 0.1mol/L aqueous hydrochloric acid; dropwise adding 0.8ml of E1 solution (containing 0.400g E1) prepared in the step (2), continuously stirring at 65 ℃ for reaction for 4 hours after 20 minutes, removing part of solvent under reduced pressure, and continuously reacting until gel is formed to obtain the dual-stimulus-responsive organosilicon hydrogel material NB-PEGS 2-1 (E1 and PEG) 2000 -S 1 The molar ratio of (2:1).
The compressive strength of the organosilicon-based hydrogel material prepared by the embodiment can reach 0.460MPa.
The infrared spectrogram of the organosilicon-based hydrogel material prepared in the embodiment is shown in fig. 1, which proves that the target material of the invention is successfully prepared.
Application example 4
2.40ml of PEG prepared in example 4, step (1) at 0.310g/ml 2000 -S 1 The solvent was removed from the tetrahydrofuran solution under reduced pressure to give 0.744g of PEG 2000 -S 1 1ml of water and 0.6ml of 2mg/ml of Doxorubicin (DOX) aqueous solution were added to dissolve PEG 2000 -S 1 The hydrolysis was continued with stirring at 70 ℃ for 30 minutes and the pH of the system solution was adjusted to = 3 using 0.1mol/L aqueous hydrochloric acid; dropwise adding 0.8ml of E1 solution (containing 0.400g of E1) prepared in the step (2) in the example 4, continuously stirring at 70 ℃ for 3 hours after 20 minutes, and continuously reacting until drug-loaded gel is formed after reducing pressure for 30 minutes to remove part of solvent to obtain the silicone-based drug-loaded gel material DOX@NB-PEGS 2-1 。
Preparing the above gel into trisections, wherein the two gel parts are respectively placed in 30ml buffer solution with pH=7.4 (normal physiological condition) and pH=2, and 3ml buffer is taken out at regular intervalsFlushing and timely supplementing the buffer solution with the same volume. The third part of medicine carrying gel is placed in 30ml of buffer solution with pH=7.4 (normal physiological condition), illumination is respectively carried out for 10 minutes at 1, 6, 9 and 13 hours (365 nm), illumination is not applied in other time, 3ml of buffer solution is taken out at regular intervals, and buffer solution with the same volume is timely supplemented; and sampling for 1, 6, 9 and 13 hours, and resampling after illumination is finished. Analysis of 3ml of DOX-containing buffer removed at the various intervals described above was performed by UV-vis, DOX@NB-PEGS 2-1 The organosilicon-based hydrogel can release the drug doxorubicin continuously for up to 90 hours in the pH=2 environment, and the drug is released completely. In "on-off" mode, NB-PEGS 2-1 The silicone-based hydrogels exhibited timed and quantitative light-controlled drug release behavior as shown in fig. 2.
Comparative example 1
PEG 2000 Preparation of S, E2 is as described in example 2.
2.40ml of 0.330g/ml PEG 2000 The solvent was removed from the S tetrahydrofuran solution under reduced pressure to give 0.792g of PEG 2000 -S; 1.30ml of water was added to dissolve PEG 2000 S, stirring hydrolysis at 65 ℃ for 30 minutes, and adjusting the system solution ph=3 using 0.1mol/L aqueous hydrochloric acid; 0.200g of E2 (absolute ethanol is not added) is added dropwise, and after 20 minutes, the E2 forms granular gel in the reaction system.
Comparative example 1 shows that the addition of an ethanol co-solvent plays an important role in controlling the hydrolytic condensation of the photo-responsive silane monomer to produce a uniform, stable hydrogel, and its properties.
Comparative example 2
PEG 2000 Preparation of S, E2 is as described in example 2.
2.40ml of 0.330g/ml PEG 2000 The solvent was removed from the S tetrahydrofuran solution under reduced pressure to give 0.792g of PEG 2000 -S; 1.30ml of water was added to dissolve PEG 2000 S, stirring hydrolysis at 65 ℃ for 30 minutes, and adjusting the system solution ph=10 using 0.1mol/L aqueous hydrochloric acid; 0.40ml of E2 solution (containing 0.200g of E2) prepared in the step (2) is added dropwise, and after 20 minutes, the hard block resin appears in the reaction system quickly.
Comparative example 2 shows that the pH of a suitable system is important for controlling the hydrolytic condensation process of silanes and has a great influence on the properties of the prepared materials.
Claims (10)
1. The dual stimulus responsive silicone-based hydrogel material is characterized in that the silicone-based hydrogel material is a polymer with a cross-linked network structure; the organosilicon-based hydrogel material is prepared by hydrolysis polycondensation reaction of photo-responsive bridged silane and silane modified polyether;
the photo-responsive bridged silane has the structural formula: x (SiR) 1 R 2 R 3 ) 2 ；
Wherein R is 1 And R is 2 Each independently selected from one of methoxy or ethoxy, R 3 One selected from methyl, ethyl, phenyl, methoxy or ethoxy; x has the structure shown below:
the silane modified polyether is silane modified polyethylene glycol or silane modified polyethylene glycol-co-propylene glycol copolymer.
2. The dual stimulus-responsive silicone-based hydrogel material of claim 1, comprising one or more of the following conditions:
i. the silane modified polyethylene glycol-co-propylene glycol copolymer has the structure shown below:
(R 4 R 5 R 6 )Si(CH 2 ) 3 NHOCOCH 2 CH 2 O(CH 2 CH 2 O) m (CH 2 CH(CH 3 )O) n CH 2 CH(CH 3 )OCONH(CH 2 ) 3 Si(R 4 R 5 R 6 )，
(R 4 R 5 R 6 )Si(CH 2 ) 3 NHOCNHCH 2 CH 2 O(CH 2 CH 2 O) m (CH 2 CH(CH 3 )O) n CH 2 CH(CH 3 )NHCONH(CH 2 ) 3 Si(R 4 R 5 R 6 )，
or alternatively, the first and second heat exchangers may be,
(R 4 R 5 R 6 )Si(CH 2 ) j O(CH 2 CH 2 O) m (CH 2 CH(CH 3 )O) n (CH 2 ) j Si(R 4 R 5 R 6 )；
wherein R is 4 ，R 5 Each independently selected from one of methoxy or ethoxy, R 6 One selected from methyl, ethyl, phenyl, methoxy or ethoxy; m=1-180; n=1-135; j=3 or 5;
ii. The silane-modified polyethylene glycol has the structure shown below:
(R 4 R 5 R 6 )Si(CH 2 ) 3 NHOCOCH 2 CH 2 O(CH 2 CH 2 O) m CH 2 CH 2 OCONH(CH 2 ) 3 Si(R 4 R 5 R 6 )
wherein R is 4 ，R 5 Each independently selected from one of methoxy or ethoxy, R 6 One selected from methyl, ethyl, phenyl, methoxy or ethoxy; preferably, R 6 Selected from methyl; wherein m=45-90;
iii, photo-responsive bridged silane formula, R 1 And R is 2 Each independently selected from one of methoxy or ethoxy, R 3 Selected from methyl groups.
3. A method of preparing a dual stimulus-responsive silicone-based hydrogel material as claimed in any one of claims 1 or 2, comprising the steps of:
(1) Polyether and reactive organosilane S in solvent A 1 Obtaining silane modified polyether through reaction; the polyether is polyethylene glycol or polyethylene glycol-co-propylene glycol copolymer;
(2) In solvent B, in the presence of a base,oxidizing the compound of the formula I by potassium permanganate to obtain a compound of the formula II; in a solvent C, in the presence of borane, carrying out reduction reaction on the compound of the formula II to obtain a compound of the formula III; in a solvent D, under the action of triethylamine, reacting the compound shown in the formula III with chloroacetyl chloride to obtain a compound shown in the formula IV; in solvent E, under the action of triethylamine, a compound of formula IV and an active silane S 2 Obtaining photo-responsive bridging silane through reaction;
(3) Dissolving silane modified polyether in water, performing hydrolysis reaction, and then adjusting the pH value to be acidic; and dropwise adding an ethanol solution of photo-responsive bridging silane, and reacting until gel is formed, thus obtaining the dual-stimulus responsive organosilicon-based hydrogel material.
4. A method of preparing a dual stimulus-responsive silicone-based hydrogel material according to claim 3, comprising in step (1) one or more of the following conditions:
i. the number average molecular weight of the polyethylene glycol-co-propylene glycol copolymer is 1000-8000 g/mol; has the following structure:
HOCH 2 CH 2 O(CH 2 CH 2 O) m (CH 2 CH(CH 3 )O) n CH 2 CH(CH 3 )OH；
NH 2 CH 2 CH 2 O(CH 2 CH 2 O) m (CH 2 CH(CH 3 )O) n CH 2 CH(CH 3 )NH 2 ；
CH 2 ＝CHCH 2 CH 2 CH 2 O(CH 2 CH 2 O) m (CH 2 CH(CH 3 )O) n CH 2 CH 2 CH 2 CH＝CH 2 the method comprises the steps of carrying out a first treatment on the surface of the Or, CH 2 ＝CHCH 2 O(CH 2 CH 2 O) m (CH 2 CH(CH 3 )O) n CH 2 CH＝CH 2 ；
Wherein m=1-180; n=1-135;
ii. The number average molecular weight of the polyethylene glycol is 2000-4000 g/mol; has the following structure: HOCH 2 CH 2 O(CH 2 CH 2 O) m CH 2 CH 2 OH; wherein m=45-90.
5. A method of preparing a dual stimulus-responsive silicone-based hydrogel material according to claim 3, comprising in step (1) one or more of the following conditions:
i. solvent A is tetrahydrofuran or acetonitrile; the volume ratio of the mass of polyether to the solvent A is 1:1 to 8;
ii. Reactive organosilanes S 1 Is isocyanate propyl triethoxy silane, isocyanate propyl trimethoxy silane, isocyanate propyl methyl dimethoxy silane, isocyanate propyl methyl diethoxy silane, siH (R) 4 R 5 R 6 ) (hydrosilane) or Cl (CH) 2 ) 3 Si(R 4 R 5 R 6 ) (chlorohydrocarbyl silane); preferably isocyanate propyltriethoxysilane, isocyanate propylmethyldimethoxysilane, isocyanate propyltrimethoxysilane or isocyanate propylmethyldiethoxysilane;
iii, polyether and reactive organosilane S 1 The molar ratio of (2) is 1:2-2.5;
iv, the reaction temperature is 40-80 ℃, the reaction time is 2-6h, and the reaction is carried out under the condition of stirring; preferably, the reaction temperature is 60-70 ℃;
v, reactive organosilanes S 1 Is added into a system containing polyether in a dropwise manner; the dripping is carried out under the stirring condition;
vi, drying polyether under reduced pressure, and then mixing with active organosilane S 1 And (3) reacting.
6. A method of preparing a dual stimulus-responsive silicone-based hydrogel material as claimed in claim 3, comprising in step (2) one or more of the following conditions:
i. solvent B is water; the mass ratio of the compound of the formula I to the solvent B is 5-10g/L; the mass ratio of the compound of the formula I to the alkali is 1:0.4-0.5; the mass ratio of the compound of the formula I to the potassium permanganate is 1:4-5; the oxidation reaction temperature is 80-100 ℃ and the oxidation reaction time is 40-50h;
ii. Solvent C is tetrahydrofuran; the mass ratio of the compound of the formula II to the solvent C is 0.01-0.5g/mL; the mass ratio of the borane to the compound of the formula II is 0.1-1:1, a step of; the reduction reaction temperature is room temperature, and the reduction reaction time is 40-60 h; the borane is added into a reaction system containing the compound of the formula II and the solvent C in a dropwise manner;
iii, solvent D is acetonitrile; the mass ratio of the compound of the formula III to the solvent D is 0.02-0.05g/mL; the mass ratio of the triethylamine to the compound of the formula III is 1-1.5:1; the mass ratio of the compound of the formula III to the chloroacetyl chloride is 1:1.1-1.5; the reaction temperature is 60-70 ℃ and the reaction time is 3-8h;
iv, solvent E is acetonitrile; the volume ratio of the mass of the compound of the formula IV to the solvent E is 0.01-0.1g/mL; the mass ratio of the triethylamine to the compound of the formula IV is 0.5-1.2:1; compounds of formula IV and reactive silanes S 2 The molar ratio of (2) is 1:2-2.5; the reaction temperature is 60-80 ℃ and the reaction time is 4-8h;
v, reactive silane S 2 Is NH 2 (CH 2 ) 3 Si(R 1 R 2 R 3 )，R 1 And R is 2 Each independently selected from one of methoxy or ethoxy, R 3 One selected from methyl, ethyl, phenyl, methoxy or ethoxy; preferably aminopropyl methyldimethoxy silane or aminopropyl methyldiethoxy silane.
7. A method of preparing a dual stimulus-responsive silicone-based hydrogel material as claimed in claim 3, comprising in step (3) one or more of the following conditions:
i. the mass ratio of the silane modified polyether to the water is 0.1-9:1, preferably 0.3-3:1; the hydrolysis reaction temperature is 30-90 ℃, preferably 60-70 ℃; the hydrolysis reaction time is 20-50min;
ii. Adjusting the pH value to 2-3 by using a hydrochloric acid aqueous solution with the mass concentration of 0.05-1 mol/L;
iii, the concentration of the ethanol solution of the photo-responsive bridging silane is 0.1-1g/mL;
iv, the mass ratio of the silane modified polyether to the photo-responsive bridging silane is 1-9:1, preferably 1-4:1;
v, the dropping speed of the photo-responsive bridging silane is 0.01-0.1 ml/min;
vi, after the completion of the addition of the photo-responsive bridging silane, the reaction temperature is 30 to 90 ℃, preferably 60 to 70 ℃.
8. Use of a dual stimulus-responsive silicone-based hydrogel material according to any one of claims 1 or 2, as carrier for loading drug molecules to obtain a dual stimulus-responsive drug-loaded silicone-based hydrogel material for achieving a sustained release and a targeted release of the drug.
9. The use of a dual stimulus-responsive silicone-based hydrogel material as recited in claim 8, wherein the method of application comprises the steps of:
(1) The preparation method of the silane modified polyether is as claimed in claim 3;
(2) The method for preparing the photo-responsive bridging silane is as claimed in claim 3;
(3) Dissolving silane modified polyether in water, adding a drug, fully mixing and dispersing uniformly, carrying out hydrolysis reaction, and then regulating the pH value to be acidic; and dropwise adding an ethanol solution of photo-responsive bridging silane, and reacting until gel is formed, thus obtaining the dual-stimulus responsive drug-loaded organosilicon-based hydrogel material.
10. The use of a dual stimulus-responsive silicone-based hydrogel material according to claim 9, wherein the drug is doxorubicin, paclitaxel, tetracycline, epirubicin, etimicin or pirarubicin; the mass ratio of the medicine to the silane modified polyether is 0.0001-1:1.
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| CN112047974A (en) * | 2020-09-09 | 2020-12-08 | 山东大学 | Photodegradable bridged silane and preparation method thereof |
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| CN111303431A (en) * | 2020-04-06 | 2020-06-19 | 刘云晖 | Self-repairable organic silicon hydrogel and preparation method thereof |
| CN112047974A (en) * | 2020-09-09 | 2020-12-08 | 山东大学 | Photodegradable bridged silane and preparation method thereof |
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| Title |
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| BABAK RADI ET AL: "Controlled Poly(ethylene glycol) Network Structures through Silsesquioxane Cross-Links Formed by Sol-Gel Reactions", 《MACROMOLECULES》, vol. 43, 31 December 2010 (2010-12-31), pages 9957 - 9963, XP055243505, DOI: 10.1021/ma101511p * |
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