CN107320841A - A kind of macromolecule micropin and its preparation method and application - Google Patents
A kind of macromolecule micropin and its preparation method and application Download PDFInfo
- Publication number
- CN107320841A CN107320841A CN201710654098.6A CN201710654098A CN107320841A CN 107320841 A CN107320841 A CN 107320841A CN 201710654098 A CN201710654098 A CN 201710654098A CN 107320841 A CN107320841 A CN 107320841A
- Authority
- CN
- China
- Prior art keywords
- macromolecule
- micropin
- needle body
- macromolecule micropin
- solution
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
Classifications
-
- 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
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L31/00—Materials for other surgical articles, e.g. stents, stent-grafts, shunts, surgical drapes, guide wires, materials for adhesion prevention, occluding devices, surgical gloves, tissue fixation devices
- A61L31/04—Macromolecular materials
- A61L31/048—Macromolecular materials obtained by reactions only involving carbon-to-carbon unsaturated bonds
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L31/00—Materials for other surgical articles, e.g. stents, stent-grafts, shunts, surgical drapes, guide wires, materials for adhesion prevention, occluding devices, surgical gloves, tissue fixation devices
- A61L31/08—Materials for coatings
- A61L31/10—Macromolecular materials
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B33—ADDITIVE MANUFACTURING TECHNOLOGY
- B33Y—ADDITIVE MANUFACTURING, i.e. MANUFACTURING OF THREE-DIMENSIONAL [3-D] OBJECTS BY ADDITIVE DEPOSITION, ADDITIVE AGGLOMERATION OR ADDITIVE LAYERING, e.g. BY 3-D PRINTING, STEREOLITHOGRAPHY OR SELECTIVE LASER SINTERING
- B33Y80/00—Products made by additive manufacturing
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L2400/00—Materials characterised by their function or physical properties
- A61L2400/12—Nanosized materials, e.g. nanofibres, nanoparticles, nanowires, nanotubes; Nanostructured surfaces
-
- 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
- A61M2037/0023—Drug applicators using microneedles
-
- 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
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
- Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Heart & Thoracic Surgery (AREA)
- Epidemiology (AREA)
- Surgery (AREA)
- Vascular Medicine (AREA)
- Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Dermatology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Manufacturing & Machinery (AREA)
- Materials Engineering (AREA)
- Medical Informatics (AREA)
- Anesthesiology (AREA)
- Biomedical Technology (AREA)
- Hematology (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Medicinal Preparation (AREA)
- Media Introduction/Drainage Providing Device (AREA)
Abstract
The present invention relates to a kind of macromolecule micropin and its preparation method and application, which solve existing micropin and be difficult to prepare and the undesirable technical problem of administering effect, the macromolecule micropin in the present invention is provided with substrate, substrate is provided with needle body, and needle body is provided with nano coating；Substrate and needle body are made up of the mixture of high polymer material and initiator；Nano coating is made up of high polymer material.Invention also provides its preparation method and application.Present invention can apply to the delivering of biopharmaceutical macromolecular drug.
Description
Technical field
The present invention relates to doser, a kind of macromolecule micropin for large biological molecule transdermal delivery is related in particular to
And its preparation method and application.
Background technology
In recent years, biopharmaceutical macromolecular drug is achieved in the development advanced by leaps and bounds, preceding 100 well selling medicines in the whole world in 2006 only
Macromolecular drug in having 24, then by 2016, this numeral rises to 47 kinds.It is raw in well selling medicine top ten lists in 2015
Thing macromolecular drug is even more to have accounted for 8 seats.The delivering mode of the most frequently used biopharmaceutical macromolecular drug is drug administration by injection, including
Intravenous injection and be subcutaneously injected, but drug administration by injection usually requires the monitoring of doctor, produce larger pain, patient dependence compared with
, there is infection risk etc. in difference.
The non-injection administration mode of biopharmaceutical macromolecular drug was widely paid close attention in the last few years, the side reported at present
Formula includes nasal-cavity administration, pulmonary administration, oral administration, cutaneous penetration etc..Common macromolecular drug such as peptide and protein,
Their molecular weight is often thousands of to hundreds of thousands, 1 to 100 nanometer of molecular diameter, thus is difficult as small-molecule drug one
Sample is by spreading through tissue surface and then being absorbed and used.Non-injection administration mode includes cutaneous penetration, and maximum challenge exists
In the bioavilability for how improving medicine.
Microneedle cutaneous in recent years to achieve huge progress, micropin can be createed by piercing through horny layer of epidermis
Micro-nano duct enters corium and hypodermis beneficial to medicine, and then is absorbed to improve biological utilisation by capillary
Degree.Common micropin has metal, and the various material such as silicon and macromolecule is made according to unlike material using corresponding processing method,
Including micro-nano processing, metal form is processed, the method such as gaseous plasma lithography, but any of the above method often has
The limitation such as have that machining accuracy is low, cost is high, manufacturing procedure is cumbersome, be difficult to mass produce.
The challenge of another biopharmaceutical macromolecular drug delivering is how to deliver strong dose thing and keep its bioactivity.
Compared to small-molecule drug, macromolecular drug, especially antibody and hormone class medicine generally require delivering higher dosage (micro-
Gram to milligram magnitude) medicine to reach expected therapeutic effect.Due to most biopharmaceutical macromolecular drugs in vivo and in vitro
The medicine of unstability, higher concentration or higher dosage is difficult to load on macromolecule micropin conventional again.While in order to ensure
The bioactivity of the biopharmaceutical macromolecular drug of load to microneedle configuration, it is necessary to carry out subtly designing and optimizing.
The content of the invention
The present invention be exactly in order to solve existing micropin be difficult prepare and the undesirable technical problem of administering effect there is provided one kind
Rational in infrastructure, administering effect is good and the macromolecule micropin that easily prepares and its preparation method and application.
Therefore, the present invention provides a kind of macromolecule micropin, macromolecule micropin is provided with substrate, and substrate is provided with needle body, needle body
It is provided with nano coating；Substrate and the needle body are made up of the mixture of high polymer material and initiator；Nano coating is by high score
Sub- material is constituted.
It is preferred that, needle body shape is cone, class is conical or many pyramids, and the whole height of needle body is 100-2000 μ
M, the base diameter of needle body is 100-1000 μm；The length of side of substrate or a diameter of 1-100mm, needle body integrated array are located at the base
Bottom, array specification is 1mm × 1mm-1000mm × 1000mm, and the needle point spacing of needle body is 100-5000 μm.
It is preferred that, high polymer material is light initiation polymerization monomer, and it is triethylene glycol diacrylate, Tricyclodecane Dimethanol
One or more in diacrylate, pentaerythritol diacrylate, the PEG diacrylate of different molecular weight.
It is preferred that, initiator is light trigger, and it is 2,2- dimethoxy -2- phenyl acetophenones, benzenediol (2,4,6- tri-
Methyl benzoyl)-phosphine oxide, the one or more in 2- hydroxyls -4'- (2- hydroxyl-oxethyls) -2- methylbenzenes third.
Invention also provides the preparation method of macromolecule micropin, it comprises the following steps：(1) by light initiation polymerization list
(scope is 100 by certain mass ratio for body and initiator：(0.1-20)) mixing, it is poured into the print cartridge of stereolithography 3D printing
In；(2) designed macromolecule microneedle configuration is inputted in 3D printer, starts printing；(3) it is to be printed to terminate, sample is taken out,
Remove the solution on surface：(4) sample is post-processed 10-30 minutes as under uviol lamp；(5) received in the modification of macromolecule microneedle surface
Rice coating.
It is preferred that, step (5) comprises the following steps：High-molecular coating is added dropwise on clean macromolecule microneedle surface molten
Liquid, after solution is uniformly paved with microneedle surface, removes excess surface solution, macromolecule micropin is positioned over -80 DEG C small more than 2
When；Macromolecule micropin is immersed in cyclohexane solvent, is drawn off after 10 minutes, application of vacuum 1-4 hours.
It is preferred that, high-molecular coating solution is PLA, fine polypropylene, gelatin, one kind of nylon；Described coating solution
Solvent be tetrahydrofuran, methanol, dimethylformamide, one kind of dimethyl sulfoxide (DMSO).
Present invention simultaneously provides application of the macromolecule micropin in delivering biopharmaceutical macromolecular drug.
It is preferred that, biopharmaceutical macromolecular drug be thyroid gland by element, insulin, clostridium botulinum, interferon, monoclonal antibody,
One or more in collagen, heparin, hyaluronic acid, gelatin and tissue growth factor.
It is preferred that, application of the macromolecule micropin in delivering biopharmaceutical macromolecular drug comprises the following steps：(a) by cleaning
The dry macromolecule micropin with nano coating is immersed in the biomolecule aqueous solution, is placed at room temperature on shaking table 1-4 hours；
(b) excess surface solution is removed, macromolecule micropin is positioned in freeze dryer, is handled 1-5 hours；(c) dried finished product is low
Warm sealing preserve is standby.
Macromolecule micropin of the present invention is due to nano surface coating, can significantly improve large biological molecule medicine
The load capacity of thing simultaneously can keep its bioactivity for a long time；By adjusting the preparation parameter and technique of coating, it can design
Go out different loads amount and different rates of release, the control release for active bio macromolecular drug.Other needle body is by biofacies
Capacitive macromolecule is made, and is had no toxic side effect into hypodermis, can while avoiding the other materials micropin such as metal, glass, silicon
The risk of the broken needle of energy.3D printing of the present invention prepares the process of macromolecule micropin relative to existing preparation side
Method, simple with process conditions, processing is quick, the advantage such as precision height, is suitable for producing in enormous quantities, can be widely used in
Skin passs medicine field.
Brief description of the drawings
Fig. 1 is macromolecule micropin preparation flow figure of the present invention；
Fig. 2 is macromolecule micropin light field optical microscope of the present invention；
Fig. 3 is macromolecule micropin electron microscope of the present invention；
Fig. 4 is that macromolecule microneedle drug (parathormone) of the present invention loads spirogram；
Fig. 5 is macromolecule microneedle drug (parathormone) drug release patterns in vitro figure of the present invention；
Fig. 6 is the bioactivity of medicine (parathormone) room temperature that macromolecule micropin of the present invention is loaded；
Fig. 7 is the external rat skin test chart of macromolecule micropin of the present invention；
Fig. 8 is the stained slice figure for the rat skin cross section that macromolecule micropin of the present invention is treated.
Embodiment
According to following embodiments, the present invention may be better understood.However, as it will be easily appreciated by one skilled in the art that real
Apply the content described by example and be merely to illustrate the present invention, without should be also without limitation on this hair described in claims
It is bright.
In the present invention stereolithography 3D printer equipment used include Projet1200, Projet6000HD,
Formlabs Form 2、DWS Lab Xfab。
Embodiment 1：3D printing method prepares macromolecule micropin
By light initiation polymerization monomer, (the present embodiment is not limited by taking PEG diacrylate (550 molecular weight) as an example
In this.Other monomers may be selected from triethylene glycol diacrylate, Tricyclodecane Dimethanol diacrylate, pentaerythrite diacrylate
One or more in ester, the PEG diacrylate of different molecular weight) and light trigger (the present embodiment is with benzenediol
(2,4,6- trimethylbenzoyl)-phosphine oxide) exemplified by, but not limited to this.Other light triggers may be selected from 2,2- dimethoxys-
2- phenyl acetophenones, benzenediol (2,4,6- trimethylbenzoyls)-phosphine oxide, 2- hydroxyls -4'- (2- hydroxyl-oxethyls) -2-
One or more in methylbenzene third) according to certain mass ratio, (the present embodiment is with 100：Exemplified by 1, but not limited to this.It is light-initiated poly-
Closing monomer and initiator scope in mass ratio includes 100：(0.1-20)) mixed, clear liquid is obtained after being sufficiently stirred for
In body, the print cartridge that the liquid is poured into ProJet1200 3D printers.Design on computers and input macromolecule microneedle array
Form parameter, starts 3D printer and prints designed micropin.After the completion of printing, surface residual liquid is removed with isopropanol punching
Body.Dry clean micropin is placed in uviol lamp lower 10 minutes, makes its full cross-linked.After reaction terminates, vacuum drying macromolecule micropin
(Fig. 1).It is intact using observation by light microscope form, the high macromolecule micropin (Fig. 2) of precision is made.
Embodiment 2：The surface modification of nanofiber
Illustrate the surface modification method of nanofiber to gather left lactic acid/tetrahydrofuran solution example, but this method application
High-molecular coating solution is not limited only to gather left lactic acid/tetrahydrofuran solution, in addition to other family macromolecule coating solutions, such as molten
Matter includes PLA, fine polypropylene, gelatin, one kind of nylon；Solvent includes tetrahydrofuran, methanol, dimethylformamide, diformazan
One or more of Polymer Solutions of base sulfoxide.Poly- left lactic acid/tetrahydrofuran solution of 2% mass fraction is configured, it is fully molten
Clear liquid is obtained after solution.It is added dropwise on clean macromolecule microneedle surface and gathers left lactic acid solution, treats that solution is uniformly paved with
After microneedle surface, excess surface solution is removed, macromolecule micropin is positioned in -80 DEG C of refrigerators 4 hours.It is afterwards that macromolecule is micro-
Pin is immersed in cyclohexane solvent, is drawn off after 10 minutes, vacuum drying treatment 4 hours.Seen using high power electron microscope
Examine the uniform nanofiber coating (Fig. 3) on macromolecule microneedle surface.
Embodiment 3：The loading and release profiles of biopharmaceutical macromolecular drug
The stowage of biopharmaceutical macromolecular drug, but the large biological molecule of this method application are introduced by taking parathormone as an example
Medicine is not limited only to parathormone, applies also for element, insulin, meat by other class biopharmaceutical macromolecular drugs, such as thyroid gland
One kind in bacillus venenosus, interferon, monoclonal antibody, collagen, heparin, hyaluronic acid, gelatin and tissue growth factor
Or it is several.
Parathormone (PTH) is that U.S.'s food and the only approved macromolecular for osteoporosis therapy of Bureau of Drugs Supervision are more
Peptide medicament.Current therapeutic scheme is daily hypodermic injection PTH to treat osteoporosis.The present invention will use macromolecule micro-
Pin delivers PTH as the painless convenient therapeutic scheme of one kind.By the leaching of the macromolecule micropin with nano coating of clean dried
Not in PTH solution (1% mass fraction), it is placed at room temperature on shaking table 4 hours.Excess surface solution is removed, macromolecule is micro-
Pin is positioned in freeze dryer, is handled 5 hours.Dry finished product low temperature seal is saved backup.As a comparison, without nano coating
Macromolecule micropin be also to load PTH with above-mentioned same method.
Macromolecule micropin with nano coating and do not have cated macromolecule micropin in drug load and insoluble drug release
The two important aspects of curve are compared.Two groups of samples are placed in the phosphate buffered saline (PBS) of same volume
In, solution example is collected at designed time point, institute in solution is measured using EUSA (ELISA) afterwards
The PTH discharged content, and then obtain drug loading (Fig. 4) and drug release patterns (Fig. 5).Data display has nanometer
The macromolecule micropin of coating is not than having the PTH of cated 18.6 times of macromolecule micropin multi-load, while realizing up to 150 hours
Continuous slow release.
Using PTH competent cell hot-wire arrays, the macromolecule micropin can effectively preserve up to 90% at room temperature
The PTH of load bioactivity is up to 6 months as long as (Fig. 6).
Embodiment 4：The skin test of macromolecule micropin
By the macromolecule micropin light press prepared on the skin of back of rat, micropin is removed after 5 minutes, can be observed
To the vestige (Fig. 7) of micropin.Hematoxylin eosin staining tissue staining section (Fig. 8) clearly illustrates that macromolecule microneedle array can
Effectively to puncture epidermis, skin corium is entered, can be for realizing efficient transdermal delivery macromolecular drug.
Claims (10)
1. a kind of macromolecule micropin, it is characterized in that the macromolecule micropin is provided with substrate, the substrate is provided with needle body, the pin
Body is provided with nano coating；The substrate and the needle body are made up of the mixture of high polymer material and initiator；The nanometer
Coating is made up of high polymer material.
2. macromolecule micropin according to claim 1, it is characterised in that the needle body shape is cone, class cone or
Many pyramids, the whole height of the needle body is 100-2000 μm, and the base diameter of the needle body is 100-1000 μm；The base
The length of side at bottom or a diameter of 1-100mm, the needle body integrated array are located at the substrate, and array specification is 1mm × 1mm-
1000mm × 1000mm, the needle point spacing of the needle body is 100-5000 μm.
3. macromolecule micropin according to claim 1, it is characterised in that the high polymer material is light initiation polymerization monomer,
Including triethylene glycol diacrylate, Tricyclodecane Dimethanol diacrylate, pentaerythritol diacrylate, different molecular weight
One or more in PEG diacrylate.
4. macromolecule micropin according to claim 1, it is characterised in that the initiator is light trigger, including 2,2- bis-
Methoxyl group -2- phenyl acetophenones, benzenediol (2,4,6- trimethylbenzoyls)-phosphine oxide, 2- hydroxyls -4'- (2- '-hydroxyethoxies
Base) one or more in -2- methylbenzenes third.
5. the preparation method of the macromolecule micropin as described in Claims 1-4 is any, it is characterized in that comprising the following steps：
(1) by light initiation polymerization monomer and initiator in mass ratio 100：(0.1-20) is mixed, and is poured into stereolithography 3D and is beaten
In the print cartridge of print；
(2) designed macromolecule microneedle configuration is inputted in 3D printer, starts printing；
(3) it is to be printed to terminate, sample is taken out, the solution on surface is removed；
(4) sample is post-processed as under uviol lamp；
(5) nano coating is modified in macromolecule microneedle surface.
6. the preparation method of macromolecule micropin according to claim 5, it is characterised in that the step (5) includes following step
Suddenly：High-molecular coating solution is added dropwise on clean macromolecule microneedle surface, after solution is uniformly paved with microneedle surface, table is removed
Face redundant solution, less than -80 DEG C are positioned over by macromolecule micropin；Macromolecule micropin is immersed in cyclohexane solvent, then will
It takes out, application of vacuum.
7. the preparation method of macromolecule micropin according to claim 6, it is characterised in that the high-molecular coating solution
Solute includes PLA, fine polypropylene, gelatin, one kind of nylon；The solvent of described coating solution includes tetrahydrofuran, first
Alcohol, dimethylformamide, the one or more of dimethyl sulfoxide (DMSO).
8. application of the macromolecule micropin in delivering biopharmaceutical macromolecular drug as described in claim 1 to 5 is any.
9. application of the macromolecule micropin according to claim 8 in delivering biopharmaceutical macromolecular drug, it is characterised in that institute
Stating biopharmaceutical macromolecular drug includes element, insulin, clostridium botulinum, interferon, monoclonal antibody, collagen, liver by thyroid gland
One or more in element, hyaluronic acid, gelatin and tissue growth factor.
10. application of the macromolecule micropin according to claim 9 in delivering biopharmaceutical macromolecular drug, it is characterized in that including
Following steps：
(a) the macromolecule micropin with nano coating of clean dried is immersed in the biomolecule aqueous solution, be placed at room temperature
On shaking table；
(b) excess surface solution is removed, macromolecule micropin is positioned in freeze dryer and handled；
(c) dried finished product low temperature seal is saved backup.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201710654098.6A CN107320841A (en) | 2017-08-03 | 2017-08-03 | A kind of macromolecule micropin and its preparation method and application |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201710654098.6A CN107320841A (en) | 2017-08-03 | 2017-08-03 | A kind of macromolecule micropin and its preparation method and application |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN107320841A true CN107320841A (en) | 2017-11-07 |
Family
ID=60225351
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201710654098.6A Pending CN107320841A (en) | 2017-08-03 | 2017-08-03 | A kind of macromolecule micropin and its preparation method and application |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN107320841A (en) |
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN108325064A (en) * | 2018-03-02 | 2018-07-27 | 莆田学院 | A kind of sustained release micropin and preparation method thereof |
| CN109125912A (en) * | 2018-08-09 | 2019-01-04 | 武汉大学 | A kind of 3D printing microneedle patch and preparation method thereof that Intelligent blood sugar is adjusted |
| CN110193082A (en) * | 2018-02-27 | 2019-09-03 | 辽宁成大生物股份有限公司 | A kind of preparation method of sterile rabies vaccine coating micropin |
| CN110507900A (en) * | 2019-08-15 | 2019-11-29 | 莆田学院 | A kind of sustained release micropin and preparation method thereof, equipment |
| CN113423381A (en) * | 2018-12-03 | 2021-09-21 | 艾里奥治疗公司 | Improved delivery of large agents |
Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2009009004A1 (en) * | 2007-07-09 | 2009-01-15 | Apogee Technology, Inc. | Coating formulations including polyphosphazene polyelectrolytes and biologically active agents and asperities coated with such formulations |
| CN102333565A (en) * | 2008-10-16 | 2012-01-25 | 昆士兰大学 | A method and associated apparatus for coating projections on a patch assembly |
| KR101136739B1 (en) * | 2009-06-15 | 2012-04-19 | 주식회사 라파스 | Multi-functional Hybrid Microstructure and Process for Preparing the Same |
| CN104302349A (en) * | 2012-03-16 | 2015-01-21 | 新加坡国立大学 | A novel method to fabricate polymeric microneedles |
| CN105126242A (en) * | 2015-07-26 | 2015-12-09 | 北京化工大学 | Polymer coating microneedle patch convenient for antibiotic skin testing and preparation method thereof |
| CN105797266A (en) * | 2016-03-07 | 2016-07-27 | 李媚 | Micro-structure body and preparation method thereof |
-
2017
- 2017-08-03 CN CN201710654098.6A patent/CN107320841A/en active Pending
Patent Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2009009004A1 (en) * | 2007-07-09 | 2009-01-15 | Apogee Technology, Inc. | Coating formulations including polyphosphazene polyelectrolytes and biologically active agents and asperities coated with such formulations |
| CN102333565A (en) * | 2008-10-16 | 2012-01-25 | 昆士兰大学 | A method and associated apparatus for coating projections on a patch assembly |
| KR101136739B1 (en) * | 2009-06-15 | 2012-04-19 | 주식회사 라파스 | Multi-functional Hybrid Microstructure and Process for Preparing the Same |
| CN104302349A (en) * | 2012-03-16 | 2015-01-21 | 新加坡国立大学 | A novel method to fabricate polymeric microneedles |
| CN105126242A (en) * | 2015-07-26 | 2015-12-09 | 北京化工大学 | Polymer coating microneedle patch convenient for antibiotic skin testing and preparation method thereof |
| CN105797266A (en) * | 2016-03-07 | 2016-07-27 | 李媚 | Micro-structure body and preparation method thereof |
Non-Patent Citations (3)
| Title |
|---|
| 梅兴国: "《微载体药物递送***》", 30 November 2009 * |
| 王洪武: "《肺癌：可防，可治》", 30 May 2007 * |
| 陈玉祥: "《分子药剂学》", 31 January 2010 * |
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110193082A (en) * | 2018-02-27 | 2019-09-03 | 辽宁成大生物股份有限公司 | A kind of preparation method of sterile rabies vaccine coating micropin |
| CN108325064A (en) * | 2018-03-02 | 2018-07-27 | 莆田学院 | A kind of sustained release micropin and preparation method thereof |
| CN109125912A (en) * | 2018-08-09 | 2019-01-04 | 武汉大学 | A kind of 3D printing microneedle patch and preparation method thereof that Intelligent blood sugar is adjusted |
| CN113423381A (en) * | 2018-12-03 | 2021-09-21 | 艾里奥治疗公司 | Improved delivery of large agents |
| CN110507900A (en) * | 2019-08-15 | 2019-11-29 | 莆田学院 | A kind of sustained release micropin and preparation method thereof, equipment |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN107320841A (en) | A kind of macromolecule micropin and its preparation method and application | |
| Zhang et al. | Fabrication, evaluation and applications of dissolving microneedles | |
| Kim et al. | Implantable powder-carrying microneedles for transdermal delivery of high-dose insulin with enhanced activity | |
| Zhu et al. | Combined silk fibroin microneedles for insulin delivery | |
| Seong et al. | A self-adherent, bullet-shaped microneedle patch for controlled transdermal delivery of insulin | |
| Fan et al. | Responsive Hydrogel Microcarrier‐Integrated Microneedles for Versatile and Controllable Drug Delivery | |
| KR101881609B1 (en) | Microneedle assembly formulation for skin treatment | |
| Zhu et al. | Preparation of asiaticoside-loaded coaxially electrospinning nanofibers and their effect on deep partial-thickness burn injury | |
| Yang et al. | A scalable fabrication process of polymer microneedles | |
| EP2769749B1 (en) | Microneedle deposition technique | |
| TWI445555B (en) | Dressing comprising active components of centella asiatica and use of the same | |
| CN108403617A (en) | Triamcinolone acetonide solubility micropin and preparation method thereof | |
| CN106902453B (en) | A kind of needle body is solvable and the insoluble microneedle preparation method of substrate | |
| CN108601727A (en) | A kind of method of printing speed micropin patch | |
| CN104667346A (en) | Preparation method of biodegradable nano-microsphere and application | |
| CN108653198A (en) | It is a kind of can cutaneous penetration hydrogel and its preparation method and application | |
| Lee et al. | Promoting diabetic wound therapy using biodegradable rhPDGF-loaded nanofibrous membranes: CONSORT-compliant article | |
| Hiew et al. | Bioinspired short peptide hydrogel for versatile encapsulation and controlled release of growth factor therapeutics | |
| US20230381096A1 (en) | Core-shell microneedle patch for h2o2 and ph cascade-triggered insulin delivery | |
| US20190060522A1 (en) | Natural Polymer-Derived Scaffold Material and Methods for Production Thereof | |
| CN111558128A (en) | Soluble microneedle array carrying scar repairing medicine and preparation method | |
| Chen et al. | Cold-atmospheric plasma augments functionalities of hybrid polymeric carriers regenerating chronic wounds: In vivo experiments | |
| Xu et al. | Engineering air-in-water emulsion as adaptable multifunctional sealant | |
| CN108478520A (en) | A kind of coating microneedle array and preparation method thereof accurately controlling drugloading rate | |
| CN106176573B (en) | A kind of solubility hollow microneedles and preparation method thereof |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| RJ01 | Rejection of invention patent application after publication | ||
| RJ01 | Rejection of invention patent application after publication |
Application publication date: 20171107 |