CN109621181A - A kind of compound micropin of photothermal response and preparation method thereof - Google Patents
A kind of compound micropin of photothermal response and preparation method thereof Download PDFInfo
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
- A61M37/00—Other apparatus for introducing media into the body; Percutany, i.e. introducing medicines into the body by diffusion through the skin
- A61M37/0015—Other apparatus for introducing media into the body; Percutany, i.e. introducing medicines into the body by diffusion through the skin by using microneedles
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- 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
- A61K41/0028—Disruption, e.g. by heat or ultrasounds, sonophysical or sonochemical activation, e.g. thermosensitive or heat-sensitive liposomes, disruption of calculi with a medicinal preparation and ultrasounds
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- 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
- A61K47/02—Inorganic compounds
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- A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
- A61K47/42—Proteins; Polypeptides; Degradation products thereof; Derivatives thereof, e.g. albumin, gelatin or zein
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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
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0019—Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
- A61K9/0021—Intradermal administration, e.g. through microneedle arrays, needleless injectors
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
- A61M37/00—Other apparatus for introducing media into the body; Percutany, i.e. introducing medicines into the body by diffusion through the skin
- A61M37/0015—Other apparatus for introducing media into the body; Percutany, i.e. introducing medicines into the body by diffusion through the skin by using microneedles
- A61M2037/0053—Methods for producing microneedles
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Abstract
The invention discloses compound micropins of a kind of photothermal response and preparation method thereof.Methacrylation gelatin (GelMA) is made using gelatin as substrate, by being grafted with methacrylic anhydride in the preparation method；Again using methacrylation gelatin as template, copper ammon solution is copper source, and vulcanized sodium is sulphur source, synthesizes copper sulphide nano particles at room temperature；By the way that n-isopropyl acrylamide is added and imports the dimethyl silicone polymer template that mould obtains again, photo-crosslinking solidification is carried out under ultraviolet light, obtains that skin can be punctured, photo-thermal can be responded and discharge the compound micropin material of responsiveness of drug in skin.The compound micropin is not only easy to puncture skin layer, can respond photo-thermal and deliver drug on demand, and have good biocompatibility；The characteristics of it is simple and easy to prepare copper sulphide nano particles process simultaneously, avoids the use such as surfactant, meets Green Chemistry.
Description
Technical field
The present invention relates to organic/inorganic nano hybrid composite material preparation technical fields, and in particular to a kind of photothermal response
Compound micropin of property and preparation method thereof.
Background technique
Cutaneous penetration overcomes oral administration bring digestion degradation problem and drug administration by injection bring is bled and pain is asked
Topic, but due to the obstruction of keratoderma, Traditional transdermal patch is difficult to Medicated Permeation to enter in blood.Current solution
Fat-soluble auxiliary agent is added in drug mainly to promote Medicated Permeation, however, the obstruction of keratoderma makes drug be difficult to reach
To required dosage.
In recent years, to solve the above-mentioned problems, there is scholar that drug is coated on micropin, skin keratin is punctured by micropin
Drug delivery is entered subcutaneous tissue by layer, to solve the problem on obstacle of cuticula.Simultaneously as micropin only has several hundred microns
Long, it punctures skin in minimally invasive form, will not touch subcutaneous pain nerve, the problem of so as to avoid pain.
Traditional metal micro-needle and silicon materials micropin energy Quick carrying drug enters skin inner layer, but its load capacity is few, holds
It easily causes broken needle and remains in body and damage.In contrast, polymer micro needle material has good biocompatibility,
Biodegradability, and material source is extensive, and carrying drug ratio is high, and preparation is simple, has great potential as micropin material.Polymerization
Object micropin punctures after carrying drug into skin, and syringe needle slowly dissolves the drug of release package within a certain period of time.However this is
A kind of passively drug delivery formats, can not be according to the dosage of sick Man's Demands and physiological environment variation control drug.
Summary of the invention
Prepare simple it is an object of the present invention to provide a kind of, biocompatibility is good, biodegradable photo-thermal micropin and
Preparation method.
The purpose of the present invention is realized at least through one of following technical scheme.
A kind of preparation method of the compound micropin of photothermal response, includes the following steps:
(1) methacrylic anhydride modified gelatin
Gelatin is dissolved in phosphate buffer, gelatin solution is sufficiently dissolved to obtain in a heated condition, then instills methyl-prop dropwise
Olefin(e) acid acid anhydride is reacted；The phosphate buffer termination synthermal with the heating condition is continuously added after reaction to react,
Methacrylation gelatin is lyophilized to obtain after dialysis, for use；
(2) copper sulphide nano particles are synthesized
Copper-bath is taken, obtains copper ammon solution after ammonium hydroxide is added, adds the methacryl that step (1) freeze-drying obtains
Change gelatin；Then sodium sulfide solution is instilled dropwise, and dialysis obtains methacrylation gelatin/copper sulfide suspension sufficiently after reaction
Liquid, for use；
(3) dimethyl silicone polymer template is prepared
Curing agent is instilled dimethyl silicone polymer, liquid is poured into micropin mold after mixing well, is subsequently placed under baking oven and dries
It does to solidification, takes off and dimethyl silicone polymer template can be obtained；
(4) micropin is synthesized
N-isopropyl acrylamide is added in methacrylation gelatin/copper sulfide suspension, light is added after being sufficiently mixed
Initiator, then dimethyl silicone polymer template is poured into, it is placed under ultraviolet lamp and is crosslinked, taking off can be obtained with photothermal response
Compound micropin.
Further, gelatin solution concentration as described in step (1) is 8 ~ 16%g/mL, is dissolved under the heating condition
Temperature is 40 ~ 60 DEG C, and the amount of methacrylic anhydride is 8 ~ 16%v/v of gelatin solution, and the instillation time is 3 ~ 5min, reaction time
For 30 ~ 60min, phosphate buffer volume used in stopped reaction is to be initially added for gelatinolytic phosphate-buffered
2 ~ 4 times of liquid product.
Further, copper-bath concentration mass fraction described in step (2) is 0.1 ~ 0.5%g/mL, ammonia concn 10
~ 15%v/v, the methacrylation gelatin being lyophilized account for 10% ~ g/mL of percentage of copper ammon solution, and sodium sulfide solution concentration is
0.4 ~ 1M, vulcanized sodium account for 0.1 ~ 1% g/mL of copper ammon solution.
Further, the mass ratio of curing agent described in step (3) and dimethyl silicone polymer is 1:11 ~ 1:9.
Further, the temperature used is dried described in step (3) as 40-60 DEG C.
Further, step (3) curing agent is silicon rubber curing agent.
Further, step (4) photoinitiator uses photoinitiator Irgacure 2959.
Further, n-isopropyl acrylamide described in step (4) accounts for methacrylation gelatin/copper sulfide suspension
Percentage is 1 ~ 10% g/ml, and 2959 concentration of photoinitiator Irgacure accounts for methacrylation gelatin/copper sulfide suspension
Percentage is 0.5 ~ 1% g/mL, and uv power is 200 ~ 400W.
The compound micropin of photothermal response that the above-mentioned preparation method of the present invention obtains, the compound micropin of the photothermal response can be used for transdermal
Drug is delivered, and drug delivery amount can be controlled according to patient demand.The compound micropin of photothermal response, a height of 40 ~ 600 μ of needle
M, needle width are 10 ~ 100 μm.
Compared with prior art, the invention has the following advantages that
(1) preparation method environmental protection of the present invention, simple and easy to do, the feature of composite green chemistry.
(2) photothermal response micropin prepared by the present invention works well for the puncture of skin, and responsiveness delivers Drug
Can be good, feeling of pain will not be caused.
(3) it is good to prepare biocompatibility by the present invention, in vivo biodegradable.
Detailed description of the invention
Fig. 1 is the stereoscopic micrograph of micropin made from embodiment.
Fig. 2 is the gelatin of embodiment and the infrared spectrogram (FTIR) of methacrylation gelatin.
Fig. 3 is the uv absorption spectra of copper sulphide nano particles solution made from embodiment.
Specific embodiment
Technical solution of the present invention is described in further detail below in conjunction with specific embodiments and drawings, but reality of the invention
It applies mode and protection scope is without being limited thereto.
Embodiment 1
Gelatin (such as 1g) is dissolved in phosphate buffer with the concentration of 10%g/mL, is sufficiently dissolved under 50 DEG C of heating conditions
Gelatin solution instills methacrylic anhydride dropwise and is reacted, and the amount of dropwise addition is the 10%v/v of gelatin solution；After reaction after
It is continuous 3 times of aforementioned phosphate salt buffer volumes to be added and synthermal phosphate buffer termination reaction, it is lyophilized after dialysis stand-by.
0.2%g/mL copper-bath is configured, obtains copper ammon solution after the ammonium hydroxide for accounting for copper-bath 12%v/v is added, then
The methacrylation gelatin of above-mentioned freeze-drying is added to copper ammon solution with the amount of 12g/mL.Then the sulphur of 0.6M concentration is instilled dropwise
Change sodium solution, vulcanized sodium is made to account for the 0.2%g/mL of copper ammon solution, methacrylation gelatin/copper sulfide of sufficiently dialysing to obtain after reaction
Suspension, for use.
184 curing agent of DOW CORNING SYLGARD 1:9 in mass ratio is instilled dimethyl silicone polymer, by liquid after mixing well
Body pours into micropin mold, is subsequently placed in lower 60 DEG C of baking oven to solidifying, takes off and dimethyl silicone polymer template can be obtained.
N-isopropyl acrylamide is added to by 3%g/mL by copper sulfide suspension, and 0.5%g/mL is added after being sufficiently mixed
Photoinitiator Irgacure, reload dimethyl silicone polymer template, be placed under the ultraviolet lamp of 300w and be crosslinked, taking off can obtain
To the compound micropin with photothermal response.Fig. 1 is the stereoscopic micrograph of micropin made from embodiment 1, as shown in Figure 1, made
Standby micropin is in pyramid shape, the more regular unification of pattern.Fig. 2 is the gelatin (gelatin) and methacrylation of embodiment 1
The infrared spectrogram (FTIR) of gelatin (gelma), the absorption vibration peak for C=C double bond occur at 1640cm-1 in figure illustrate successfully to close
At methacrylation gelatin.Fig. 3 is the uv absorption spectra of copper sulphide nano particles solution made from embodiment 1, system
Standby copper sulphide nano particles have strong absorption in the near infrared region, the absorption with copper sulphide nano particles reported in the literature
Peak position is almost the same (ACS nano, 2015,9 (7): 7085-7096).A height of 40 ~ 600 μm of the compound needle needle, needle is wide
It is 10 ~ 100 μm.The compound micropin is conducive to puncture skin layer, can respond photo-thermal and deliver drug on demand, and have good life
Object compatibility；It is simple and easy that copper sulphide nano particles process is prepared simultaneously, is avoided the use such as surfactant, is met greenization
The characteristics of.
Embodiment 2
Gelatin (such as 0.8g) is dissolved in phosphate buffer with the concentration of 8%g/mL, is sufficiently dissolved under 40 DEG C of heating conditions
Gelatin solution instills methacrylic anhydride dropwise and is reacted, and the amount of dropwise addition is the 8%v/v of gelatin solution；After reaction after
Continuous 2 times of aforementioned phosphate salt buffer volumes to be added and synthermal phosphate buffer termination reaction, freeze-drying obtains first after dialysis
The acrylated gelatin of base.
0.1%g/mL copper-bath is configured, obtains copper ammon solution after the ammonium hydroxide for accounting for copper-bath 10%v/v is added, then
The methacrylation gelatin of above-mentioned freeze-drying is added to copper ammon solution with 10g/mL amount.Then the vulcanization of 0.4M concentration is instilled dropwise
Sodium solution makes vulcanized sodium account for the 0.1%g/mL of copper ammon solution, sufficiently dialyses after reaction stand-by, obtains methacrylation gelatin/sulphur
Change copper suspension.
184 curing agent of DOW CORNING SYLGARD 1:9 in mass ratio is instilled dimethyl silicone polymer, by liquid after mixing well
Body pours into micropin mold, is subsequently placed in lower 40 DEG C of baking oven and is dried to solidification, takes off and dimethyl silicone polymer template can be obtained.
N-isopropyl acrylamide is added in methacrylation gelatin/copper sulfide suspension by 1%g/mL, sufficiently
The photoinitiator Irgacure 2959 of 0.5%g/mL is added after mixing, reloads dimethyl silicone polymer template, is placed in 200w's
It is crosslinked under ultraviolet lamp, takes the compound micropin that can be obtained with photothermal response off.The stereoscopic micrograph of obtained micropin is joined
According to Fig. 1, prepared micropin is in pyramid shape, the more regular unification of pattern.Gelatin (gelatin) and methacrylation gelatin
(gelma) referring to Fig. 2, the absorption vibration peak for C=C double bond occur at 1640cm-1 in figure is illustrated as infrared spectrogram (FTIR)
Function has synthesized methacrylation gelatin.The uv absorption spectra (referring to Fig. 3) of copper sulphide nano particles solution obtained, system
Standby copper sulphide nano particles have strong absorption in the near infrared region, the absorption with copper sulphide nano particles reported in the literature
Peak position is almost the same (ACS nano, 2015,9 (7): 7085-7096).
Embodiment 3
Gelatin (such as 1.2g) is dissolved in phosphate buffer with the concentration of 12%g/mL, is sufficiently dissolved under 50 DEG C of heating conditions
Gelatin solution is obtained, methacrylic anhydride is instilled dropwise and is reacted, the amount of dropwise addition is 12%v/v；4 are continuously added after reaction
Times aforementioned phosphate salt buffer volume and synthermal phosphate buffer terminates reaction, is lyophilized stand-by after dialysis.
0.3%g/mL copper-bath is configured, is added after accounting for copper-bath 13%v/v ammonium hydroxide and obtains copper ammon solution, then with
The methacrylation gelatin of above-mentioned freeze-drying is added to copper ammon solution for the amount of 15g/mL.Then the vulcanization of 0.6M concentration is instilled dropwise
Sodium solution makes vulcanized sodium account for the 0.5%g/mL of copper ammon solution, sufficiently dialyse after reaction methacrylation gelatin/copper sulfide is outstanding
Supernatant liquid, for use.
184 1:10 in mass ratio of curing agent DOW CORNING SYLGARD is instilled dimethyl silicone polymer, it will after mixing well
Liquid pours into micropin mold, is subsequently placed at 50 DEG C of baking oven and is dried to solidification, takes off and dimethyl silicone polymer template can be obtained.
N-isopropyl acrylamide is added in methacrylation gelatin/copper sulfide suspension by 5%g/mL, sufficiently mixed
The photoinitiator Irgacure of 0.7%g/mL is added after conjunction, reloads dimethyl silicone polymer template, is placed in the ultraviolet lamp of 300w
The compound micropin that can be obtained with photothermal response is taken in lower crosslinking off.The stereoscopic micrograph of obtained micropin referring to Fig.1,
Prepared micropin is in pyramid shape, the more regular unification of pattern.Gelatin (gelatin) and methacrylation gelatin
(gelma) referring to Fig. 2, the absorption vibration peak for C=C double bond occur at 1640cm-1 in figure is illustrated as infrared spectrogram (FTIR)
Function has synthesized methacrylation gelatin.The uv absorption spectra (referring to Fig. 3) of copper sulphide nano particles solution obtained, system
Standby copper sulphide nano particles have strong absorption in the near infrared region, the absorption with copper sulphide nano particles reported in the literature
Peak position is almost the same (ACS nano, 2015,9 (7): 7085-7096).
Embodiment 4
Gelatin (such as 1.5g) is dissolved in phosphate buffer with the concentration of 15%g/mL, is sufficiently dissolved under 60 DEG C of heating conditions
Gelatin solution is obtained, methacrylic anhydride is instilled dropwise and is reacted, the amount of dropwise addition is the 8%v/v of gelatin solution；After reaction
It continuously adds 3 times of aforementioned phosphate salt buffer volumes and synthermal phosphate buffer terminates reaction, be lyophilized after dialysis stand-by.
0.4%g/mL copper-bath is configured, obtains copper ammon solution after the ammonium hydroxide for accounting for copper-bath 15%v/v is added, then
The methacrylation gelatin of above-mentioned freeze-drying is added to copper ammon solution with the amount of 17g/mL.Then the sulphur of 0.8M concentration is instilled dropwise
Change sodium solution, vulcanized sodium is made to account for the 0.7%g/mL of copper ammon solution, sufficiently obtains methacrylation gelatin/copper sulfide after reaction and suspend
Liquid, for use.
The 1:11 in mass ratio of DOW CORNING SYLGARD 184 is instilled dimethyl silicone polymer, falls liquid after mixing well
Needle mould has in a subtle way, is subsequently placed in lower 60 DEG C of baking oven and is dried to solidification, takes off and dimethyl silicone polymer template can be obtained.
N-isopropyl acrylamide is added in methacrylation gelatin/copper sulfide suspension by 7%g/mL, sufficiently mixed
The photoinitiator Irgacure2959 of 1%g/mL is added after conjunction, reloads dimethyl silicone polymer template, is placed in the ultraviolet of 400w
It is crosslinked under lamp, takes the compound micropin that can be obtained with photothermal response off.The stereoscopic micrograph of obtained micropin is referring to figure
1, prepared micropin is in pyramid shape, the more regular unification of pattern.Gelatin (gelatin) and methacrylation gelatin
(gelma) referring to Fig. 2, the absorption vibration peak for C=C double bond occur at 1640cm-1 in figure is illustrated as infrared spectrogram (FTIR)
Function has synthesized methacrylation gelatin.The uv absorption spectra (referring to Fig. 3) of copper sulphide nano particles solution obtained, system
Standby copper sulphide nano particles have strong absorption in the near infrared region, the absorption with copper sulphide nano particles reported in the literature
Peak position is almost the same (ACS nano, 2015,9 (7): 7085-7096).
Embodiment 5
Gelatin is dissolved in phosphate buffer with the concentration of (such as 1.6g) 16%g/mL, is sufficiently dissolved under 60 DEG C of heating conditions,
It instills methacrylic anhydride dropwise to be reacted, the amount of dropwise addition is the 16%v/v of gelatin solution；4 times are continuously added after reaction
Aforementioned phosphate salt buffer volume and synthermal phosphate buffer, which terminate, to react, and is lyophilized after dialysis stand-by.
0.5%g/mL copper-bath is configured, is added after accounting for copper-bath 15%v/v ammonium hydroxide and obtains copper ammon solution, then with
The methacrylation gelatin of above-mentioned freeze-drying is added to copper ammon solution for the amount of 20g/mL.Then the vulcanized sodium of 1M concentration is instilled dropwise
Solution makes vulcanized sodium account for the 1%g/mL of copper ammon solution, sufficiently obtains methacrylation gelatin/copper sulfide suspension after reaction, to
With.
184 1:11 in mass ratio of curing agent DOW CORNING SYLGARD is instilled dimethyl silicone polymer, it will after mixing well
Liquid pours into micropin mold, is subsequently placed in lower 60 DEG C of baking oven and is dried to solidification, takes off and dimethyl silicone polymer template can be obtained.
N-isopropyl acrylamide is added in methacrylation gelatin/copper sulfide suspension by 10%g/mL, sufficiently mixed
The photoinitiator Irgacure2959 of 1%g/mL is added after conjunction, reloads dimethyl silicone polymer template, is placed in the ultraviolet of 400w
Be crosslinked under lamp, take off can be obtained it is compound micro- with photothermal response.
Referring to Fig.1, prepared micropin is in pyramid shape, the more regular system of pattern to the stereoscopic micrograph of obtained micropin
One.The infrared spectrogram (FTIR) of gelatin (gelatin) and methacrylation gelatin (gelma) is referring to Fig. 2, in figure
The absorption vibration peak explanation for occurring C=C double bond at 1640cm-1 successfully synthesizes methacrylation gelatin.Copper sulfide obtained
The uv absorption spectra (referring to Fig. 3) of nano-particle solution, the copper sulphide nano particles of preparation have strongly in the near infrared region
Absorption, with the absorption peak position of copper sulphide nano particles reported in the literature it is almost the same (ACS nano, 2015,9
(7): 7085-7096).
The present invention has the copper sulphide nano particles of photothermal response using the template action synthesis of modified gelatin, passes through loading
Poly-N-isopropyl acrylamide (PNIPAM) molecule of Thermo-sensitive, and using the light-cured performance of modified gelatin, synthesis has light
The compound micropin of thermo-responsive.Change micropin and overcome the shortcomings of existing micropin, is conducive to puncture skin surface, it can be in near-infrared laser
The swelling of the lower control micropin material of response, so as to control burst size of the drug in micropin, to realize the on-demand of drug
To amount.
Claims (10)
1. a kind of preparation method of the compound micropin of photothermal response, it is characterized in that: including the following steps:
Methacrylic anhydride modified gelatin
Gelatin is dissolved in phosphate buffer, gelatin solution is sufficiently dissolved to obtain in a heated condition, then instills methyl-prop dropwise
Olefin(e) acid acid anhydride is reacted；The phosphate buffer termination synthermal with the heating condition is continuously added after reaction to react,
Methacrylation gelatin is lyophilized to obtain after dialysis, for use；
Synthesize copper sulphide nano particles
Copper-bath is taken, obtains copper ammon solution after ammonium hydroxide is added, adds the methacryl that step (1) freeze-drying obtains
Change gelatin；Then sodium sulfide solution is instilled dropwise, and dialysis obtains methacrylation gelatin/copper sulfide suspension sufficiently after reaction
Liquid, for use；
Prepare dimethyl silicone polymer template
Curing agent is instilled dimethyl silicone polymer, liquid is poured into micropin mold after mixing well, is subsequently placed under baking oven and dries
It does to solidification, takes off and dimethyl silicone polymer template can be obtained；
Synthesize micropin
N-isopropyl acrylamide is added in methacrylation gelatin/copper sulfide suspension, light is added after being sufficiently mixed
Initiator, then dimethyl silicone polymer template is poured into, it is placed under ultraviolet lamp and is crosslinked, taking off can be obtained with photothermal response
Compound micropin.
2. preparation method according to claim 1, which is characterized in that gelatin solution concentration as described in step (1) be 8 ~
16%g/mL, solution temperature is 40 ~ 60 DEG C under the heating condition, and methacrylic anhydride additional amount is the 8 ~ 16% of gelatin solution
V/v, instillation time are 3 ~ 5min, and the reaction time is 30 ~ 60min, and phosphate buffer volume used in stopped reaction is initial
2 ~ 4 times for gelatinolytic phosphate buffer volume being added.
3. preparation method according to claim 1, which is characterized in that copper-bath concentration quality described in step (2)
Score is 0.1 ~ 0.5%g/mL, and ammonium hydroxide accounts for 10 ~ 15%v/v of copper-bath, and the methacrylation gelatin being lyophilized accounts for copper
10% ~ g/mL of percentage of ammonia solution, sodium sulfide solution concentration are 0.4 ~ 1M, and vulcanized sodium accounts for 0.1 ~ 1% g/mL of copper ammon solution.
4. preparation method according to claim 1, which is characterized in that curing agent described in step (3) and poly dimethyl silicon
The mass ratio of oxygen alkane is 1:11 ~ 1:9.
5. preparation method according to claim 1, which is characterized in that dry the temperature used described in step (3) as 40-
60℃。
6. preparation method according to claim 1, which is characterized in that step (3) curing agent is silicon rubber curing agent.
7. preparation method according to claim 1, which is characterized in that step (4) photoinitiator uses photoinitiator
Irgacure 2959。
8. preparation method according to claim 1, which is characterized in that n-isopropyl acrylamide described in step (4) accounts for
Methacrylation gelatin/copper sulfide suspension percentage is 1 ~ 10% g/ml, and 2959 concentration of photoinitiator Irgacure accounts for first
The acrylated gelatin of base/copper sulfide suspension percentage is 0.5 ~ 1% g/mL, and uv power is 200 ~ 400W.
9. the compound micropin of photothermal response obtained by the described in any item preparation methods of claim 1-5, the photothermal response
Compound micropin can be used for transdermal delivery of drugs, and can control drug delivery amount according to patient demand.
10. the compound micropin of photothermal response according to claim 6, it is characterised in that a height of 40 ~ 600 μm of needle, needle width is
10~100μm。
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| CN113318269A (en) * | 2021-04-22 | 2021-08-31 | 江苏大学 | CuS nanoparticle protein hydrogel and preparation method and application thereof |
| CN113908425A (en) * | 2021-10-31 | 2022-01-11 | 江苏熙美生物科技有限公司 | Method for rapidly preparing microneedle patch |
| CN114099936A (en) * | 2021-10-31 | 2022-03-01 | 江苏熙美生物科技有限公司 | Long-acting soluble microneedle for cosmetic filling and sustained-release administration and preparation method thereof |
| CN114617964A (en) * | 2022-03-17 | 2022-06-14 | 常州大学 | Enzyme-responsive photo-thermal nano material G @ CuS and preparation method thereof |
| CN115998669A (en) * | 2023-01-10 | 2023-04-25 | 中国海洋大学 | Copper sulfide nano enzyme-antibacterial peptide-hyaluronic acid composite microneedle and preparation method and application thereof |
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| CN113908425A (en) * | 2021-10-31 | 2022-01-11 | 江苏熙美生物科技有限公司 | Method for rapidly preparing microneedle patch |
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| CN114617964A (en) * | 2022-03-17 | 2022-06-14 | 常州大学 | Enzyme-responsive photo-thermal nano material G @ CuS and preparation method thereof |
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