+

CN109364366A - Method for preparing porous polymer microneedles by template method and its application - Google Patents

Method for preparing porous polymer microneedles by template method and its application Download PDF

Info

Publication number
CN109364366A
CN109364366A CN201811104132.3A CN201811104132A CN109364366A CN 109364366 A CN109364366 A CN 109364366A CN 201811104132 A CN201811104132 A CN 201811104132A CN 109364366 A CN109364366 A CN 109364366A
Authority
CN
China
Prior art keywords
acid
phosphate
template
porous polymer
sulfate
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
Application number
CN201811104132.3A
Other languages
Chinese (zh)
Inventor
朱锦涛
柳佩
李钰策
康红杰
张连斌
王�华
杜虹瑶
陶娟
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Huazhong University of Science and Technology
Union Hospital Tongji Medical College Huazhong University of Science and Technology
Original Assignee
Huazhong University of Science and Technology
Union Hospital Tongji Medical College Huazhong University of Science and Technology
Priority date (The priority date 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 date listed.)
Filing date
Publication date
Application filed by Huazhong University of Science and Technology, Union Hospital Tongji Medical College Huazhong University of Science and Technology filed Critical Huazhong University of Science and Technology
Priority to CN201811104132.3A priority Critical patent/CN109364366A/en
Publication of CN109364366A publication Critical patent/CN109364366A/en
Pending legal-status Critical Current

Links

Classifications

    • 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
    • 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
    • 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
    • C08J9/00—Working-up of macromolecular substances to porous or cellular articles or materials; After-treatment thereof
    • C08J9/26—Working-up of macromolecular substances to porous or cellular articles or materials; After-treatment thereof by elimination of a solid phase from a macromolecular composition or article, e.g. leaching out
    • 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
    • A61M2037/0046—Solid 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
    • 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
    • C08J2201/00—Foams characterised by the foaming process
    • C08J2201/04—Foams characterised by the foaming process characterised by the elimination of a liquid or solid component, e.g. precipitation, leaching out, evaporation
    • C08J2201/042—Elimination of an organic solid phase
    • 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
    • C08J2201/00—Foams characterised by the foaming process
    • C08J2201/04—Foams characterised by the foaming process characterised by the elimination of a liquid or solid component, e.g. precipitation, leaching out, evaporation
    • C08J2201/044—Elimination of an inorganic solid phase
    • 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
    • C08J2201/00—Foams characterised by the foaming process
    • C08J2201/04—Foams characterised by the foaming process characterised by the elimination of a liquid or solid component, e.g. precipitation, leaching out, evaporation
    • C08J2201/044—Elimination of an inorganic solid phase
    • C08J2201/0442—Elimination of an inorganic solid phase the inorganic phase being a metal, its oxide or hydroxide
    • 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
    • C08J2201/00—Foams characterised by the foaming process
    • C08J2201/04—Foams characterised by the foaming process characterised by the elimination of a liquid or solid component, e.g. precipitation, leaching out, evaporation
    • C08J2201/044—Elimination of an inorganic solid phase
    • C08J2201/0444—Salts
    • 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
    • C08J2201/00—Foams characterised by the foaming process
    • C08J2201/04—Foams characterised by the foaming process characterised by the elimination of a liquid or solid component, e.g. precipitation, leaching out, evaporation
    • C08J2201/044—Elimination of an inorganic solid phase
    • C08J2201/0444—Salts
    • C08J2201/0446—Elimination of NaCl only
    • 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
    • C08J2205/00—Foams characterised by their properties
    • C08J2205/04—Foams characterised by their properties characterised by the foam pores
    • C08J2205/044—Micropores, i.e. average diameter being between 0,1 micrometer and 0,1 millimeter
    • 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
    • C08J2207/00—Foams characterised by their intended use
    • C08J2207/10—Medical applications, e.g. biocompatible scaffolds
    • 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
    • C08J2301/00—Characterised by the use of cellulose, modified cellulose or cellulose derivatives
    • C08J2301/08—Cellulose derivatives
    • C08J2301/10—Esters of organic acids
    • C08J2301/12—Cellulose acetate
    • 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
    • C08J2327/00—Characterised by the use of homopolymers or copolymers of compounds having one or more unsaturated aliphatic radicals, each having only one carbon-to-carbon double bond, and at least one being terminated by a halogen; Derivatives of such polymers
    • C08J2327/02—Characterised by the use of homopolymers or copolymers of compounds having one or more unsaturated aliphatic radicals, each having only one carbon-to-carbon double bond, and at least one being terminated by a halogen; Derivatives of such polymers not modified by chemical after-treatment
    • C08J2327/12—Characterised by the use of homopolymers or copolymers of compounds having one or more unsaturated aliphatic radicals, each having only one carbon-to-carbon double bond, and at least one being terminated by a halogen; Derivatives of such polymers not modified by chemical after-treatment containing fluorine atoms
    • C08J2327/16—Homopolymers or copolymers of vinylidene fluoride
    • 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
    • C08J2371/00—Characterised by the use of polyethers obtained by reactions forming an ether link in the main chain; Derivatives of such polymers
    • C08J2371/02—Polyalkylene oxides
    • 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
    • C08J2381/00—Characterised by the use of macromolecular compounds obtained by reactions forming in the main chain of the macromolecule a linkage containing sulfur with or without nitrogen, oxygen, or carbon only; Polysulfones; Derivatives of such polymers
    • C08J2381/06—Polysulfones; Polyethersulfones
    • 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
    • C08J2401/00—Characterised by the use of cellulose, modified cellulose or cellulose derivatives
    • C08J2401/08—Cellulose derivatives
    • C08J2401/10—Esters of organic acids
    • C08J2401/12—Cellulose acetate
    • 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
    • C08J2471/00—Characterised by the use of polyethers obtained by reactions forming an ether link in the main chain; Derivatives of such polymers
    • C08J2471/02—Polyalkylene oxides
    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08K—Use of inorganic or non-macromolecular organic substances as compounding ingredients
    • C08K3/00—Use of inorganic substances as compounding ingredients
    • C08K3/18—Oxygen-containing compounds, e.g. metal carbonyls
    • C08K3/20—Oxides; Hydroxides
    • C08K3/22—Oxides; Hydroxides of metals
    • C08K2003/2206—Oxides; Hydroxides of metals of calcium, strontium or barium
    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08K—Use of inorganic or non-macromolecular organic substances as compounding ingredients
    • C08K3/00—Use of inorganic substances as compounding ingredients
    • C08K3/18—Oxygen-containing compounds, e.g. metal carbonyls
    • C08K3/24—Acids; Salts thereof
    • C08K3/26—Carbonates; Bicarbonates
    • C08K2003/265—Calcium, strontium or barium carbonate
    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08K—Use of inorganic or non-macromolecular organic substances as compounding ingredients
    • C08K3/00—Use of inorganic substances as compounding ingredients
    • C08K3/16—Halogen-containing compounds
    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08K—Use of inorganic or non-macromolecular organic substances as compounding ingredients
    • C08K3/00—Use of inorganic substances as compounding ingredients
    • C08K3/34—Silicon-containing compounds
    • C08K3/36—Silica

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Dermatology (AREA)
  • General Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Biomedical Technology (AREA)
  • Hematology (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Anesthesiology (AREA)
  • Materials Engineering (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Medical Informatics (AREA)
  • Polymers & Plastics (AREA)
  • Organic Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Cosmetics (AREA)
  • Medicinal Preparation (AREA)

Abstract

The invention discloses the method and its application that a kind of template prepares porous polymer micropin, method includes the following steps: polymer and template are dissolved in preparing in solvent by (1) obtains polymer solution；(2) polymer solution is inserted in micropin mold；(3) solvent in gained micropin mold is removed, solid microneedles are obtained；(4) template in gained solid microneedles is removed, porous polymer micropin can be obtained.The present invention is improved by the integral process flow design to the preparation method, it is cumbersome, expensive can to solve complicated porous polymer micropin preparation process, condition harshness, technique, pore structure, size are difficult to control and the technical problems such as large-scale production and application difficult, resulting porous polymer micropin can be used in tissue fluid extraction and percutaneous dosing, such as the fields such as the extraction of Skin tissue fluid, blood and beauty, hair tonic, percutaneous dosing that is immune, treating the protein in applying, polypeptide and small-molecule drug.

Description

Template prepares the method and its application of porous polymer micropin
Technical field
The invention belongs to field of biomedical polymer materials, prepare porous polymeric more particularly, to a kind of template The method and its application of object micropin, the porous polymer micropin obtained by this method can be used in extracting the system of tissue fluid or blood Agent or the pharmaceutical preparation for preparing percutaneous dosing.
Background technique
Micropin is the three-dimensional matrix structure that the length made of silicon, metal, polymer is 25-2000 μm, needle point is tapered. Micropin is the novel minimally invasive administration tool of one kind in biomedicine field, can reach increasing through skin epidermis and skin corium The effect of strong percutaneous drug delivery.In recent years, micropin is obtained in percutaneous dosing field efficiently, safely, without advantages such as pains with it Extensive concern.
Porous micropin is usually the three-dimensional porous microneedle array structure being prepared by metal, nonmetallic or polymer.With reality Heart micropin is compared, and the cavity structure of porous micropin makes that it can be applied to transdermal drug transmitting or tissue fluid extracts, be it is a kind of very Promising medical instrument.Wherein, porous polymer micropin with its good biocompatibility and biodegradability and by Extensive concern.Porous polymer micropin can be by polymer microballoon by ultrasonic welding or in micropin external sheath porous material Method obtains.However, these preparation methods process is cumbersome, condition is harsh, higher cost, and the hole knot of conventional porous micropin Structure, size be difficult to control, be unfavorable for porous polymer micropin large scale preparation and Skin tissue fluid quantitatively extracts and percutaneously Application in administration.Therefore, it is controllable and low-cost porous that a kind of process simple mildly, pore structure, size and distribution are needed The preparation method of polymer micro needle, consequently facilitating the resulting porous polymer micropin of this method is applied to Skin tissue fluid, blood Liquid extracts, nti-freckle, crease-resistant, smoothing wrinkle, hair tonic, immune, treatment, protein or polypeptide drug the fields such as percutaneous dosing.
Summary of the invention
Aiming at the above defects or improvement requirements of the prior art, the purpose of the present invention is to provide a kind of preparation of template is more The method and its application of pore polymer micropin, wherein improved by the integral process flow design to the preparation method, and Key condition and parameter (size and template of such as template and the mass ratio of polymer) are optimized, by simple Template can be prepared on a large scale porous polymer micropin, thus can solve porous polymer micropin preparation process complexity, condition Harshness, technique are cumbersome, expensive, and pore structure, size are difficult to control and the technical problems such as large-scale production and application difficult, Resulting porous polymer micropin can be used in tissue fluid extraction and percutaneous dosing, such as Skin tissue fluid, blood extraction and beauty The fields such as the percutaneous dosing of protein, polypeptide and small-molecule drug in the application such as appearance, hair tonic, immune, treatment；Also, this Invention further preferably regulates and controls the size of template and content, to regulate and control the pore size and hole of porous polymer micropin Rate, so that the porous polymer micropin of preparation has the porous structure of pore size and adjustable porosity.
To achieve the above object, according to one aspect of the present invention, providing a kind of template, to prepare porous polymer micro- The method of needle, which comprises the following steps:
(1) polymer and template are dissolved in prepare in solvent A and obtain polymer solution；
(2) in the polymer solution filling micropin mold obtained the step (1)；
(3) solvent A in micropin mold obtained by the step (2) is removed, solid microneedles are obtained；
(4) template in solid microneedles obtained by the step (3) is removed, porous polymer micropin can be obtained.
As present invention further optimization, in the step (1), the solvent A is n,N-Dimethylformamide, diformazan Base sulfoxide, DMAC N,N' dimethyl acetamide, N-Methyl pyrrolidone, hexamethyl phosphoramide, 1,4- dioxane, nitromethane, nitre Base ethane, triethyl phosphate, trimethyl phosphate, tetramethylurea, carbon disulfide, formamide, dibutyl phthalate, tetrahydro furan Mutter, methylene chloride, acetic acid, carbon tetrachloride, methanol, ethyl alcohol, isopropanol, hexane, hexamethylene, chloroform, acetone, ethylene glycol, methyl ether, Ether, water, glycerine, 1,2- propylene glycol, n-butanol, octanol, tetrachloro-ethylene, tetrachloroethanes, fluothane hydrocarbon, dichloroethanes, pyridine One or more of mixture.
As present invention further optimization, the step (4) is specifically using heating, freeze-drying or by solid microneedles It is immersed in another solvent B to remove the template；The solvent B can dissolve the template and can not dissolve institute State polymer, specially acid solution, alkaline solution, water, tetrahydrofuran, methylene chloride, methanol, ethyl alcohol, isopropanol, hexane, One of chloroform, acetone, ethylene glycol, methyl ether, ether, water, glycerine, n-butanol, octanol, dichloroethanes, pyridine or in which Several mixtures；
The acid solution be preferably sulfuric acid, hydrochloric acid, nitric acid, phosphoric acid, acetic acid, perchloric acid, chloric acid, chlorous acid, hypochlorous acid, One of permanganic acid, hydrobromic acid, formic acid, propionic acid, butyric acid, edta solution or in which several mixtures；
The alkaline solution is preferably sodium hydroxide, potassium hydroxide, ammonium hydroxide, sodium carbonate, sodium bicarbonate, potassium carbonate, carbonic acid One of hydrogen potassium, sodium phosphate, dibastic sodium phosphate, sodium dihydrogen phosphate or in which several mixtures.
As present invention further optimization, in the step (2), material used by the micropin mold is poly- diformazan Radical siloxane, epoxy resin, polytetrafluoroethylene (PTFE), Kynoar, polypropylene, polyether sulfone, polyether-ether-ketone, hyaluronic acid, poly- second Enol, polyvinylpyrrolidone, polyethylene glycol, chitosan, sodium alginate, glucose, sodium chloride, mica, glass, silicon, poly- pair One of ethylene terephthalate, polyvinyl chloride, copper, aluminium, gold, silver, stainless steel and ice or in which several compound Object.
As present invention further optimization, in the step (1), the polymer is polyacrylonitrile, polylactic acid, poly- cream Acid-co-glycolic acid, polyarylsulfone (PAS), polyether sulfone, cellulose acetate, polyimides, polyetherimide, gathers Kynoar Amide, polyether-ether-ketone, polycarbonate, polytetrafluoroethylene (PTFE), polyvinyl chloride, polyacrylic acid, polymethylacrylic acid, polyethyleneimine, Polyvinylpyridine, polyethylene glycol, poly- isotactic propylene, cellulose esters, polystyrene, polybutadiene, polyphenylene oxide, polyurethane, bromine Change polyphenylene oxide, polyvinyl alcohol, hyaluronic acid, sodium alginate, carboxymethyl cellulose, agarose, gelatin, one of chitosan or Several blends or the copolymer being made of above-mentioned polymer.
As present invention further optimization, in the step (1), the template be inorganic salts, oxide, simple substance, One of organic molecule, ice or in which several mixtures；
The inorganic salts include chloride, sulfate, disulfate, carbonate, bicarbonate, phosphate, hydrophosphate At least one of, preferably lithium chloride, beryllium chloride, sodium chloride, magnesium chloride, aluminium chloride, potassium chloride, calcium chloride, iron chloride, chlorine Change copper, nickel chloride, manganese chloride, zinc chloride, barium chloride, lithium sulfate, beryllium sulfate, sodium sulphate, magnesium sulfate, aluminum sulfate, potassium sulfate, sulphur Sour calcium, manganese sulfate, ferric sulfate, copper sulphate, zinc sulfate, barium sulfate, lithium hydrogen sulfate, hydrogen sulfate beryllium, sodium bisulfate, magnesium bisulfate, Aluminium hydrogen sulfate, potassium acid sulfate, calcium bisulfate, barium hydrogen sulfate, lithium carbonate, beryllium carbonate, sodium carbonate, magnesium carbonate, aluminium carbonate, carbonic acid Potassium, calcium carbonate, manganese carbonate, barium carbonate, lithium bicarbonate, bicarbonate beryllium, sodium bicarbonate, magnesium bicarbonate, bicarbonate aluminium, bicarbonate Potassium, calcium bicarbonate, barium bicarbonate, lithium phosphate, beryllium phosphate, sodium phosphate, magnesium phosphate, aluminum phosphate, potassium phosphate, calcium phosphate, barium phosphate, Manganese phosphate, ferric phosphate, cupric phosphate, trbasic zinc phosphate, lithium hydrogen phosphate, beryllium hydrophosphate, dibastic sodium phosphate, magnesium monohydrogen phosphate, phosphoric acid hydrogen aluminium, phosphoric acid One of hydrogen potassium, calcium monohydrogen phosphate, barium hydrogen phosphate or in which several mixtures；
The oxide includes at least one of metal oxide, nonmetal oxide, specially beryllium oxide, oxidation Magnesium, aluminium oxide, calcium oxide, barium monoxide, manganese oxide, iron oxide, copper oxide, zinc oxide, silica, one in phosphorus pentoxide Kind or in which several mixtures；
The simple substance includes at least one of metal simple-substance, non-metal simple-substance, specially gold, magnesium, aluminium, silicon, phosphorus, calcium, One of manganese, iron, copper, zinc, barium or in which several mixtures；
The organic molecule is specially glucose, lactose, galactolipin, fructose, cholesterol, polyvinylpyrrolidone, seaweed Sour sodium, chitosan, carboxymethyl cellulose, hyaluronic acid, gelatin, agarose, glucan, polyacrylonitrile, polylactic acid, polylactic acid- Co-glycolic acid, Kynoar, polyarylsulfone (PAS), polyether sulfone, cellulose acetate, polyimides, polyetherimide, polyamides Amine, polyether-ether-ketone, polycarbonate, polyvinyl chloride, polyacrylic acid, polymethylacrylic acid, polyethyleneimine, polyvinylpyridine, One of polyethylene glycol, cellulose esters, polystyrene, polybutadiene, polyphenylene oxide, polyurethane, brominated polyphenylether, polyvinyl alcohol Or in which several mixture.
As present invention further optimization, in the polymer solution that the step (1) obtains, the polymer with The mass ratio of both templates is 19:1-1:19；The template is preferably particulate powder, and the partial size of particle is 2- 50000nm；
Preferably, the template diameter is 5 μm, and the mass ratio of both the template and described polymer is 3:2, described Described its pore size of porous polymer micropin that step (4) accordingly obtains is 4.8 μm, porosity 50%；Alternatively, the mould Plate agent diameter is 10 μm, and template and polymer quality ratio are 5:1, the porous polymer that the step (4) accordingly obtains Its pore size of micropin is 9.7 μm, porosity 83%.
As present invention further optimization, the step (2) is specifically to use be centrifuged, vacuumize, ultrasound, heating, shaking Method or several method combination one of are swung to insert the polymer solution in micropin mold；
The step (3) be specifically using be lyophilized, dry, drying, gas drying, one of supercritical fluid extraction just Method or the combination of a variety of methods are to remove the solvent A.
It is another aspect of this invention to provide that the present invention provides the sides for preparing porous polymer micropin using above-mentioned template The application for the porous polymer micropin that method is prepared, which is characterized in that specifically be applied to preparation for extract tissue fluid or The preparation of blood, or preparation have whitening Cosmetic Ingredient, anti-wrinkle cosmetic ingredient, wrinkle removal beauty treatment ingredient, spot-eliminating beauty treatment ingredient, moisturizing Cosmetic Ingredient, antibiotic, small-molecule drug, protein medicaments or traditional Chinese compound medicine percutaneous drug administration preparation, or preparation is used for The pharmaceutical preparation for treating the percutaneous dosing of diabetes, psoriasis, alopecia or superficial dermatoma disease.
Contemplated above technical scheme is with conventional ultrasound welding and in micropin outer cladding porous material through the invention The prior arts such as method compare, polymer and template are made into mixed solution, mixed solution is then filled into micropin mould In tool, demoulding obtains solid microneedles after the solution is dry, and then removing the template in solid microneedles can be obtained porous gather Closing object micropin, (removing template using solvent B is acted on using selective dissolution of the solvent B to solid microneedles constituent, molten Agent B only dissolves these templates；Solvent B is also possible to occur to the course of dissolution of template either physical change occurs Chemical change)；Porous polymer micropin is made by template in the present invention, and it is numerous to overcome preparation process in traditional preparation methods It is trivial, condition is harsh, expensive, pore structure, size and distribution poor controllability the disadvantages of.The present invention can be simple, mild, quick The porous polymer micropin is prepared on ground, is suitable for large scale preparation.The system of porous polymer micropin provided by the invention The porous polymer micropin that Preparation Method is prepared has the following characteristics that pore structure is coherent, pore size controllability is good, porosity It is adjustable；Can be used for tissue fluid, blood extracts, nti-freckle, crease-resistant, smoothing wrinkle, hair tonic, immune, treatment, protein or polypeptide drug The fields such as percutaneous dosing.
Pair the present invention prepares porous polymer micropin using template, and by regulation template, (template is used for pore, i.e., Answer pore-foaming agent) size and content, regulate and control porous polymer micropin pore size and its distribution, can prepare pore structure rule It is whole, pore size distribution is uniform, the good porous polymer micropin of controllability.
In general, through the invention it is designed above technical scheme is compared with the prior art, can obtain down and show Beneficial effect:
(1) microneedle array mold materials provided by the invention are reusable, save the cost.
(2) Biocompatibility provided by the invention for preparing porous polymer micropin is good, low in cost, is suitable for more The large scale preparation of pore polymer micropin.
(3) preparation method of porous polymer microneedle array provided by the invention, for conventional porous polymer micro needle battle array Column preparation process complexity, pore structure, size and distribution poor controllability, the problems such as technique is cumbersome and expensive, by simple Porous polymer micropin is prepared in template.This method preparation process is simple mild, low in cost, and design is strong, universality It is good.
(4) preparation method of porous polymer microneedle array provided by the invention, by changing the size of template and containing Amount can Effective Regulation porous polymer micropin pore size and porosity, and then meet different porous polymer micropins prepares need It asks.
(5) porous polymer microneedle array provided by the invention, there is bigger cavity compared with solid microneedles, and drugloading rate is higher； Compared with hollow metal micropin good biocompatibility, no skin irritatin, and preparation is more simple, and pore size and distribution controllability are more preferable.
(6) preparation method of porous polymer microneedle array provided by the invention, the porous polymer micro hole knot of preparation Structure is regular, pore size and distribution controllability are good, the porous polymer micropin especially obtained compared to other preparation methods, have with Lower feature: pore size and distribution are easy to regulate and control, and pore size controlled range is wide (a few nanoscale~tens micron), can meet in group Knit the dosed administration in the percutaneous dosing of liquid, the quantitative extraction of blood and beauty, immune, treatment, protein or polypeptide drug.
To sum up, the method for preparing porous polymer micropin the present invention is based on template is easy to operate, mild condition, at low cost It is honest and clean, it is easy to large-scale production, obtained porous polymer microneedle configuration is regular, pore structure, pore size and distribution controllability are good, easily In large-scale production, capable of efficiently solving porous polymer micropin, method is complicated during the preparation process, technique is cumbersome, price is high High, pore structure, size and distribution are difficult to control, are unable to the problem of large-scale production, can be used for preparing for extracting skin histology The preparation of liquid or blood, or preparation have whitening Cosmetic Ingredient, anti-wrinkle cosmetic ingredient, wrinkle removal beauty treatment ingredient, spot-eliminating beauty treatment ingredient, Moisturizing Cosmetic Ingredient, antibiotic, small-molecule drug, protein medicaments or traditional Chinese compound medicine percutaneous drug administration preparation, or preparation For treating the pharmaceutical preparation of the percutaneous dosing of diabetes, psoriasis, alopecia or superficial dermatoma disease.As it can be seen that the present invention is logical It crosses simple method i.e. and can be prepared on a large scale porous polymer micropin, overcome porous polymer micropin preparation process complexity, item The problems such as part is harsh, technique is cumbersome, expensive, and by the content of adjusting template agent and size to regulate and control porous polymer The pore size and porosity of micropin are made to solve the problems, such as that polymer micro needle pore structure, size and distribution are difficult to control Porous polymer micropin can be used for tissue fluid extract and percutaneous dosing in.
Detailed description of the invention
Fig. 1 is the flow chart and needle point longitudal section schematic diagram that template prepares porous polymer micropin.
Fig. 2 is the optical microscope of porous polyarylsulfone (PAS) micropin.
Fig. 3 is that micropin has pricked the optical microscope after pigskin.
Specific embodiment
In order to make the objectives, technical solutions, and advantages of the present invention clearer, with reference to the accompanying drawings and embodiments, right The present invention is further elaborated.It should be appreciated that the specific embodiments described herein are merely illustrative of the present invention, and It is not used in the restriction present invention.As long as in addition, technical characteristic involved in the various embodiments of the present invention described below Not constituting a conflict with each other can be combined with each other.
The present invention provides a kind of methods for preparing porous polymer micropin based on template.Pass through the ruler of adjusting template agent Very little and concentration can prepare the good porous polymer microneedle array of regular pore structure, size uniformity, controllability.
The method that template provided by the invention prepares porous polymer microneedle array, comprising the following steps:
(1) polymer and template are dissolved in prepare in solvent A and obtain polymer solution；
(2) in the polymer solution filling micropin mold obtained the step (1)；
(3) solvent in the polymer solution in the step (2) is removed, solid microneedles are obtained；
(4) template in solid microneedles described in the step (3) is removed, porous polymer micropin is obtained.
Can quickly prepare the microneedle array mold according to the method, preparation process is simple, mild condition, at Sheet is cheap, is suitable for large scale preparation, and the pore size and distribution controllability of resulting porous polymer micropin are good.
Porous polymer micropin provided by the invention improves the loading of drug, reduces administration number of times and wound, both It can be applied to Skin tissue fluid, blood extracts and biological cutaneous penetration, it can also be used to which nti-freckle, hair tonic, is immunized, controls crease-resistant, smoothing wrinkle The percutaneous dosing for the treatment of, protein or polypeptide drug.
The present invention obtains the porous polymer of different pore size structure and porosity by the size and content of change template Micropin.
The following are embodiments:
Embodiment 1
A kind of porous polymer microneedle array of template preparation, is prepared as follows: firstly, passing through laser ablation Polytetrafluoroethylene (PTFE) former is prepared in method；Then, Kynoar and the calcium carbonate having a size of 500nm are pressed to the mass ratio of 3:7 It is added in dimethyl sulfoxide and is configured to solution, above-mentioned solution is added drop-wise on polytetrafluoroethylene (PTFE) former, vacuumize promotion solution Into in mold；Heating, drying dimethyl sulfoxide, removing obtain the solid Kynoar micropin containing calcium carbonate；By gained reality Heart micropin is placed in the dilute nitric acid solution of 2mol/L, removes calcium carbonate nano particle, porous Kynoar micropin can be obtained.
Embodiment 2
A kind of porous polymer microneedle array of template preparation, is prepared as follows: firstly, by micro- template PDMS former is prepared；Then, polysulfones and the calcium carbonate having a size of 2 μm are added to dimethyl sulfoxide by the mass ratio of 3:7 In be configured to solution, above-mentioned solution is added drop-wise on PDMS former, ultrasound promote solution enter in mold；Dry dimethyl Asia Sulfone, removing obtain the solid polysulfones micropin containing calcium carbonate；Gained solid microneedles are placed in the dilute nitric acid solution of 2mol/L, are removed Calcium carbonate nano particle is removed, porous polysulfones micropin can be obtained.
Embodiment 3
A kind of porous polymer microneedle array of template preparation, is prepared as follows: firstly, being added by micro electronmechanical Stainless steel former is prepared in work technology；Then, polysulfones and the sodium chloride having a size of 50 μm are added to N- by the mass ratio of 3:7 It is configured to solution in methyl pyrrolidone, above-mentioned solution is added drop-wise on stainless steel former, vacuumizes and solution is promoted to enter mold In；Heating, drying N-Methyl pyrrolidone, removing obtain the solid polysulfones micropin containing sodium chloride；Gained solid microneedles are placed in In pure water, sodium chloride is removed, porous polysulfones micropin can be obtained.
Embodiment 4
A kind of porous polymer microneedle array of template preparation, is prepared as follows: firstly, by micro- template PDMS former is prepared；Then, cellulose acetate and polyethylene glycol are added in dimethyl sulfoxide by the mass ratio of 1:1 and are matched It is set to solution, above-mentioned solution is added drop-wise on PDMS former, centrifugation promotes solution to enter in mold；Freeze-drying removes dimethyl Sulfoxide, removing obtain the solid cellulose acetate micropin containing polyethylene glycol；Gained solid microneedles are placed in pure water, are removed poly- Porous cellulose acetate micropin can be obtained in ethylene glycol.
Embodiment 5
A kind of porous polymer microneedle array of template preparation, is prepared as follows: firstly, by micro- template PDMS former is prepared；Then, polysulfones and the calcium carbonate having a size of 2 μm are added to N- methylpyrrole by the mass ratio of 1:9 It is configured to solution in alkanone, above-mentioned solution is added drop-wise on PDMS former, vacuumizes and solution is promoted to enter in mold；Heating, drying N-Methyl pyrrolidone, removing obtain the solid polysulfones micropin containing calcium carbonate；Gained solid microneedles are placed in the dilute of 2mol/L In nitric acid solution, calcium carbonate nano particle is removed, porous polysulfones micropin can be obtained.
Embodiment 6
A kind of porous polymer microneedle array of template preparation, is prepared as follows: firstly, by micro- template PDMS former is prepared；Then, cellulose acetate and polyvinylpyrrolidone are added to dimethyl by the mass ratio of 19:1 It is configured to solution in sulfoxide, above-mentioned solution is added drop-wise on PDMS former, vacuumizes and solution is promoted to enter in mold；Heating, drying Dimethyl sulfoxide, removing obtain the solid cellulose acetate micropin containing polyvinylpyrrolidone；Gained solid microneedles are placed in In pure water, polyvinylpyrrolidone is removed, porous cellulose acetate micropin can be obtained.
Embodiment 7
A kind of porous polymer microneedle array of template preparation, is prepared as follows: firstly, by micro- template PDMS former is prepared；Then, cellulose acetate and glucose are added in dimethyl sulfoxide by the mass ratio of 1:19 and are matched It is set to solution, above-mentioned solution is added drop-wise on PDMS former, vacuumizes and solution is promoted to enter in mold；Heating, drying dimethyl is sub- Sulfone, removing obtain the solid cellulose acetate micropin containing glucose；Gained solid microneedles are placed in pure water, grape is removed Porous cellulose acetate micropin can be obtained in sugar.
Embodiment 8
A kind of porous polymer microneedle array of template preparation, is prepared as follows: firstly, by micro- template PDMS former is prepared；Then, polyether sulfone and the silica having a size of 500nm are added to diformazan by the mass ratio of 3:7 It is configured to solution in base sulfoxide, above-mentioned solution is added drop-wise on PDMS former, ultrasound promotes solution to enter in mold；Heating, drying Dimethyl sulfoxide, removing obtain the solid polyether sulfone micropin containing silica；Gained solid microneedles are placed in the hydrogen of 2mol/L In sodium hydroxide solution, Nano particles of silicon dioxide is removed, porous polyether sulfone micropin can be obtained.
Embodiment 9
A kind of porous polymer microneedle array of template preparation, is prepared as follows: firstly, by micro- template PDMS former is prepared；Then, polyether sulfone and the silica having a size of 500nm are added to diformazan by the mass ratio of 3:7 It is configured to solution in base sulfoxide, above-mentioned solution is added drop-wise on PDMS former, ultrasound promotes solution to enter in mold；Heating, drying Dimethyl sulfoxide, removing obtain the solid polyether sulfone micropin containing silica；Gained solid microneedles are placed in 10-4Mol/L's In sodium hydroxide solution, Nano particles of silicon dioxide is removed, porous polyether sulfone micropin can be obtained.
Embodiment 10
A kind of porous polymer microneedle array of template preparation, is prepared as follows: firstly, by micro- template PDMS former is prepared；Then, polyether sulfone and the silica having a size of 500nm are added to diformazan by the mass ratio of 3:7 It is configured to solution in base sulfoxide, above-mentioned solution is added drop-wise on PDMS former, ultrasound promotes solution to enter in mold；Heating, drying Dimethyl sulfoxide, removing obtain the solid polyether sulfone micropin containing silica；Gained solid microneedles are placed in the hydrogen of 20mol/L In sodium hydroxide solution, Nano particles of silicon dioxide is removed, porous polyether sulfone micropin can be obtained.
Embodiment 11
A kind of porous polymer microneedle array of template preparation, is prepared as follows: firstly, by micro- template PDMS former is prepared；Then, polyether sulfone and the calcium oxide having a size of 2 μm are added to N, N- diformazan by the mass ratio of 3:7 It is configured to solution in base formamide, above-mentioned solution is added drop-wise on PDMS former, ultrasound promotes solution to enter in mold；Heating is dried Dry n,N-Dimethylformamide, removing obtain the solid polyether sulfone micropin containing calcium oxide；Gained solid microneedles are placed in 10- 4In the dilute nitric acid solution of mol/L, calcium oxide nanoparticle is removed, porous polyether sulfone micropin can be obtained.
Embodiment 12
A kind of porous polymer microneedle array of template preparation, is prepared as follows: firstly, by micro- template PDMS former is prepared；Then, polyether sulfone and the barium carbonate having a size of 2 μm are added to N, N- diformazan by the mass ratio of 3:7 It is configured to solution in base formamide, above-mentioned solution is added drop-wise on PDMS former, vacuumizes and solution is promoted to enter in mold；Heating N,N-Dimethylformamide is dried, removing obtains the solid polyether sulfone micropin containing barium carbonate；Gained solid microneedles are placed in In the dilute nitric acid solution of 12mol/L, barium carbonate nanoparticle is removed, porous polyether sulfone micropin can be obtained.
Embodiment 13
A kind of porous polymer microneedle array of template preparation, is prepared as follows: firstly, by micro- template PDMS former is prepared；Then, polyether sulfone and the sodium carbonate having a size of 2nm are added to N, N- diformazan by the mass ratio of 3:7 It is configured to solution in base formamide, above-mentioned solution is added drop-wise on PDMS former, vacuumizes and solution is promoted to enter in mold；Heating N,N-Dimethylformamide is dried, removing obtains the solid polyether sulfone micropin containing sodium carbonate；Gained solid microneedles are placed in In the dilute nitric acid solution of 0.1mol/L, sodium carbonate nanoparticle is removed, porous polyether sulfone micropin can be obtained.
Embodiment 14
Porous polyether sulfone micropin is prepared using the method for embodiment 1, inserts it into pre-prepd containing 1mg/ In the agar hydrogel of the 3wt% of mL rhodamine B, observe under the microscope.
Under the microscope it can clearly be seen that the needle point of porous polyether sulfone micropin is white, insertion before being inserted into agar gel After become red, red is the color of Model Molecule rhodamine B, illustrates that porous polymer micropin can draw model drug and divide Son.
Embodiment 15
Porous polyether sulfone micropin is prepared using the method for embodiment 1, rhodamine B is loaded into porous micropin, it will It is inserted on the smooth fresh mouse skin of preprepared depilation, small under the microscope in fluorescence microscopy after a period of time Mouse skin.
It observes under an optical microscope, the murine skin surface after effect has apparent hole, remaining skin is intact, table Bright porous polymer micropin can effectively pierce through mouse skin.Similarly, can be observed under fluorescence microscope, it is small after effect Mouse skin surface has apparent green fluorescence, and other parts show black, illustrate that green fluorescence is porous polymer microneedle After skin, what rhodamine B was formed at the hole that micropin leaves, illustrate that porous polymer micropin can effectively pierce through skin.
As it can be seen that compared with prior art, porous polymer microneedle array, pore structure made from template of the present invention It is regular, pore size is uniform, controllability is good；The method can be used for the large-scale production of porous polymer microneedle array；It is resulting The preparation for extracting tissue fluid or blood can be prepared separately in porous polymer micropin, can also with existing drug or have The effective component of beauty functions is loaded, and preparation is used for the drug of antibiotic skin test, or prepare and be administered for small-molecule drug, The drug of protide administration or Chinese medicine compound prescription administration, or preparation have beauty for whitening, crease-resistant, smoothing wrinkle, nti-freckle or moisturizing The preparation of the percutaneous dosing of Rongcheng point, or preparation is for treating the percutaneous of diabetes, psoriasis, alopecia or superficial dermatoma disease The drug of administration, so that it is applied to tissue fluid, blood extraction, antibiotic skin test, small-molecule drug administration, protide administration, in The administration of medicine compound, the percutaneous dosing of the Cosmetic Ingredients such as whitening, crease-resistant, smoothing wrinkle, nti-freckle, moisturizing and diabetes, psoriasis, alopecia And the percutaneous dosing of the diseases such as superficial dermatoma, it is quantitatively extracted for tissue fluid, blood, nti-freckle, hair tonic, is exempted from crease-resistant, smoothing wrinkle Epidemic disease, treatment, protein or polypeptide drug the fields such as percutaneous dosing.
As it will be easily appreciated by one skilled in the art that the foregoing is merely illustrative of the preferred embodiments of the present invention, not to The limitation present invention, any modifications, equivalent substitutions and improvements made within the spirit and principles of the present invention should all include Within protection scope of the present invention.

Claims (9)

1.一种模板法制备多孔聚合物微针的方法，其特征在于，包括以下步骤：1. a method for preparing porous polymer microneedles by template method, is characterized in that, comprises the following steps: (1)将聚合物和模板剂溶于溶剂A中配制得到聚合物溶液；(1) dissolving polymer and templating agent in solvent A to prepare polymer solution; (2)将所述步骤(1)得到的所述聚合物溶液填入微针模具中；(2) filling the polymer solution obtained in the step (1) into the microneedle mold; (3)除去所述步骤(2)所得微针模具中的所述溶剂A，得到实心微针；(3) removing the solvent A in the microneedle mold obtained in the step (2) to obtain solid microneedles; (4)除去所述步骤(3)所得实心微针中的所述模板剂，即可得到多孔聚合物微针。(4) By removing the template agent in the solid microneedles obtained in the step (3), porous polymer microneedles can be obtained. 2.如权利要求1所述模板法制备多孔聚合物微针的方法，其特征在于，所述步骤(1)中，所述溶剂A为N,N-二甲基甲酰胺、二甲基亚砜、N,N-二甲基乙酰胺、N-甲基吡咯烷酮、六甲基磷酰胺、1,4-二氧六环、硝基甲烷、硝基乙烷、磷酸三乙酯、磷酸三甲酯、四甲基脲、二硫化碳、甲酰胺、邻苯二甲酸二丁酯、四氢呋喃、二氯甲烷、醋酸、四氯化碳、甲醇、乙醇、异丙醇、己烷、环己烷、氯仿、丙酮、乙二醇、甲醚、乙醚、水、丙三醇、1,2-丙二醇、正丁醇、辛醇、四氯乙烯、四氯乙烷、氟烷烃、二氯乙烷、吡啶中的一种或几种的混合物。2. The method for preparing porous polymer microneedles by template method according to claim 1, wherein in the step (1), the solvent A is N,N-dimethylformamide, dimethylmethylene Sulfone, N,N-dimethylacetamide, N-methylpyrrolidone, hexamethylphosphoramide, 1,4-dioxane, nitromethane, nitroethane, triethyl phosphate, trimethyl phosphate Esters, tetramethylurea, carbon disulfide, formamide, dibutyl phthalate, tetrahydrofuran, dichloromethane, acetic acid, carbon tetrachloride, methanol, ethanol, isopropanol, hexane, cyclohexane, chloroform, Acetone, ethylene glycol, methyl ether, ether, water, glycerol, 1,2-propanediol, n-butanol, octanol, tetrachloroethylene, tetrachloroethane, fluoroalkane, dichloroethane, pyridine one or a mixture of several. 3.如权利要求1所述模板法制备多孔聚合物微针的方法，其特征在于，所述步骤(4)具体是采用加热、冷冻干燥或将实心微针浸没于另一种溶剂B中以除去所述模板剂；所述溶剂B能够溶解所述模板剂、且无法溶解所述聚合物，具体为酸性溶液、碱性溶液、水、四氢呋喃、二氯甲烷、甲醇、乙醇、异丙醇、己烷、氯仿、丙酮、乙二醇、甲醚、乙醚、水、丙三醇、正丁醇、辛醇、二氯乙烷、吡啶中的一种或其中几种的混合物；3. The method for preparing porous polymer microneedles by a template method according to claim 1, wherein the step (4) is specifically by heating, freeze-drying or immersing the solid microneedles in another solvent B to Remove the templating agent; the solvent B can dissolve the templating agent, but cannot dissolve the polymer, specifically acidic solution, alkaline solution, water, tetrahydrofuran, dichloromethane, methanol, ethanol, isopropanol, One or a mixture of several of hexane, chloroform, acetone, ethylene glycol, methyl ether, ether, water, glycerol, n-butanol, octanol, dichloroethane and pyridine; 所述酸性溶液优选为硫酸、盐酸、硝酸、磷酸、醋酸、高氯酸、氯酸、亚氯酸、次氯酸、高锰酸、氢溴酸、甲酸、丙酸、丁酸、乙二胺四乙酸溶液中的一种或其中几种的混合物；The acidic solution is preferably sulfuric acid, hydrochloric acid, nitric acid, phosphoric acid, acetic acid, perchloric acid, chloric acid, chlorous acid, hypochlorous acid, permanganic acid, hydrobromic acid, formic acid, propionic acid, butyric acid, ethylenediamine One or a mixture of several in the tetraacetic acid solution; 所述碱性溶液优选为氢氧化钠、氢氧化钾、氨水、碳酸钠、碳酸氢钠、碳酸钾、碳酸氢钾、磷酸钠、磷酸氢钠、磷酸二氢钠溶液中的一种或其中几种的混合物。Described alkaline solution is preferably one or several of sodium hydroxide, potassium hydroxide, ammonia water, sodium carbonate, sodium bicarbonate, potassium carbonate, potassium bicarbonate, sodium phosphate, sodium hydrogen phosphate, sodium dihydrogen phosphate solution. species mixture. 4.如权利要求1所述模板法制备多孔聚合物微针的方法，其特征在于，所述步骤(2)中，所述微针模具所采用的材料是聚二甲基硅氧烷、环氧树脂、聚四氟乙烯，聚偏氟乙烯、聚丙烯、聚醚砜、聚醚醚酮、透明质酸、聚乙烯醇、聚乙烯吡咯烷酮、聚乙二醇、壳聚糖、海藻酸钠、葡萄糖、氯化钠、云母、玻璃、硅、聚对苯二甲酸乙二醇酯、聚氯乙烯、铜、铝、金、银、不锈钢、以及冰中的一种或其中几种的复合物。4. The method for preparing porous polymer microneedles by a template method according to claim 1, wherein in the step (2), the material used in the microneedle mold is polydimethylsiloxane, cyclic Oxygen resin, polytetrafluoroethylene, polyvinylidene fluoride, polypropylene, polyethersulfone, polyetheretherketone, hyaluronic acid, polyvinyl alcohol, polyvinylpyrrolidone, polyethylene glycol, chitosan, sodium alginate, Glucose, sodium chloride, mica, glass, silicon, polyethylene terephthalate, polyvinyl chloride, copper, aluminum, gold, silver, stainless steel, and ice or one or a combination of several of them. 5.如权利要求1所述模板法制备多孔聚合物微针的方法，其特征在于，所述步骤(1)中，所述聚合物为聚丙烯腈、聚乳酸、聚乳酸-羟基乙酸共聚物、聚偏氟乙烯、聚芳砜、聚醚砜、醋酸纤维素、聚酰亚胺、聚醚酰亚胺、聚酰胺、聚醚醚酮、聚碳酸酯、聚四氟乙烯、聚氯乙烯、聚丙烯酸、聚甲基丙烯酸、聚乙烯亚胺、聚乙烯基吡啶、聚乙二醇、聚等规丙烯、纤维素酯、聚苯乙烯、聚丁二烯、聚苯醚、聚氨酯、溴化聚苯醚、聚乙烯醇、透明质酸、海藻酸钠、羧甲基纤维素、琼脂糖、明胶、壳聚糖中的一种或几种共混物或由上述聚合物构成的共聚物。5. The method for preparing porous polymer microneedles by template method according to claim 1, wherein in the step (1), the polymer is polyacrylonitrile, polylactic acid, polylactic acid-glycolic acid copolymer , polyvinylidene fluoride, polyarylsulfone, polyethersulfone, cellulose acetate, polyimide, polyetherimide, polyamide, polyetheretherketone, polycarbonate, polytetrafluoroethylene, polyvinyl chloride, Polyacrylic acid, polymethacrylic acid, polyethyleneimine, polyvinylpyridine, polyethylene glycol, polyisotactic propylene, cellulose ester, polystyrene, polybutadiene, polyphenylene ether, polyurethane, brominated poly One or more blends of phenyl ether, polyvinyl alcohol, hyaluronic acid, sodium alginate, carboxymethyl cellulose, agarose, gelatin, chitosan or a copolymer composed of the above polymers. 6.如权利要求1所述模板法制备多孔聚合物微针的方法，其特征在于，所述步骤(1)中，所述模板剂为无机盐、氧化物、单质、有机分子、冰中的一种或其中几种的混合物；所述无机盐包括氯化物、硫酸盐、硫酸氢盐、碳酸盐、碳酸氢盐、磷酸盐、磷酸氢盐中的至少一种，优选为氯化锂、氯化铍、氯化钠、氯化镁、氯化铝、氯化钾、氯化钙、氯化铁、氯化铜、氯化镍、氯化锰、氯化锌、氯化钡，硫酸锂、硫酸铍、硫酸钠、硫酸镁、硫酸铝、硫酸钾、硫酸钙、硫酸锰、硫酸铁、硫酸铜、硫酸锌、硫酸钡，硫酸氢锂、硫酸氢铍、硫酸氢钠、硫酸氢镁、硫酸氢铝、硫酸氢钾、硫酸氢钙、硫酸氢钡，碳酸锂、碳酸铍、碳酸钠、碳酸镁、碳酸铝、碳酸钾、碳酸钙、碳酸锰、碳酸钡，碳酸氢锂、碳酸氢铍、碳酸氢钠、碳酸氢镁、碳酸氢铝、碳酸氢钾、碳酸氢钙、碳酸氢钡，磷酸锂、磷酸铍、磷酸钠、磷酸镁、磷酸铝、磷酸钾、磷酸钙、磷酸钡、磷酸锰、磷酸铁、磷酸铜、磷酸锌，磷酸氢锂、磷酸氢铍、磷酸氢钠、磷酸氢镁、磷酸氢铝、磷酸氢钾、磷酸氢钙、磷酸氢钡中的一种或其中几种的混合物；6. The method for preparing porous polymer microneedles by a template method according to claim 1, wherein in the step (1), the template agent is an inorganic salt, an oxide, a simple substance, an organic molecule, or a substance in ice. One or several mixtures thereof; the inorganic salts include at least one of chloride, sulfate, hydrogen sulfate, carbonate, hydrogen carbonate, phosphate, and hydrogen phosphate, preferably lithium chloride, Beryllium chloride, sodium chloride, magnesium chloride, aluminum chloride, potassium chloride, calcium chloride, iron chloride, copper chloride, nickel chloride, manganese chloride, zinc chloride, barium chloride, lithium sulfate, sulfuric acid Beryllium, sodium sulfate, magnesium sulfate, aluminum sulfate, potassium sulfate, calcium sulfate, manganese sulfate, iron sulfate, copper sulfate, zinc sulfate, barium sulfate, lithium hydrogen sulfate, beryllium hydrogen sulfate, sodium hydrogen sulfate, magnesium hydrogen sulfate, hydrogen sulfate Aluminum, potassium hydrogen sulfate, calcium hydrogen sulfate, barium hydrogen sulfate, lithium carbonate, beryllium carbonate, sodium carbonate, magnesium carbonate, aluminum carbonate, potassium carbonate, calcium carbonate, manganese carbonate, barium carbonate, lithium hydrogen carbonate, beryllium carbonate, carbonate Sodium Bicarbonate, Magnesium Bicarbonate, Aluminum Bicarbonate, Potassium Bicarbonate, Calcium Bicarbonate, Barium Bicarbonate, Lithium Phosphate, Beryllium Phosphate, Sodium Phosphate, Magnesium Phosphate, Aluminum Phosphate, Potassium Phosphate, Calcium Phosphate, Barium Phosphate, Manganese Phosphate, One or a mixture of iron phosphate, copper phosphate, zinc phosphate, lithium hydrogen phosphate, beryllium hydrogen phosphate, sodium hydrogen phosphate, magnesium hydrogen phosphate, aluminum hydrogen phosphate, potassium hydrogen phosphate, calcium hydrogen phosphate, barium hydrogen phosphate ; 所述氧化物包括金属氧化物、非金属氧化物中的至少一种，具体为氧化铍、氧化镁、氧化铝、氧化钙、氧化钡、氧化锰、氧化铁、氧化铜、氧化锌、二氧化硅、五氧化二磷中的一种或其中几种的混合物；The oxides include at least one of metal oxides and non-metal oxides, specifically beryllium oxide, magnesium oxide, aluminum oxide, calcium oxide, barium oxide, manganese oxide, iron oxide, copper oxide, zinc oxide, and dioxide One or a mixture of silicon and phosphorus pentoxide; 所述单质包括金属单质、非金属单质中的至少一种，具体为金、镁、铝、硅、磷、钙、锰、铁、铜、锌、钡中的一种或其中几种的混合物；The element includes at least one of metal element and non-metal element, specifically one of gold, magnesium, aluminum, silicon, phosphorus, calcium, manganese, iron, copper, zinc, barium or a mixture of several thereof; 所述有机分子具体为葡萄糖、乳糖、半乳糖、果糖、胆固醇、聚乙烯吡咯烷酮、海藻酸钠、壳聚糖、羧甲基纤维素、透明质酸、明胶、琼脂糖、葡聚糖、聚丙烯腈、聚乳酸、聚乳酸-羟基乙酸共聚物、聚偏氟乙烯、聚芳砜、聚醚砜、醋酸纤维素、聚酰亚胺、聚醚酰亚胺、聚酰胺、聚醚醚酮、聚碳酸酯、聚氯乙烯、聚丙烯酸、聚甲基丙烯酸、聚乙烯亚胺、聚乙烯基吡啶、聚乙二醇、纤维素酯、聚苯乙烯、聚丁二烯、聚苯醚、聚氨酯、溴化聚苯醚、聚乙烯醇中的一种或其中几种的混合物。The organic molecules are specifically glucose, lactose, galactose, fructose, cholesterol, polyvinylpyrrolidone, sodium alginate, chitosan, carboxymethyl cellulose, hyaluronic acid, gelatin, agarose, dextran, polypropylene Nitrile, polylactic acid, polylactic acid-glycolic acid copolymer, polyvinylidene fluoride, polyarylsulfone, polyethersulfone, cellulose acetate, polyimide, polyetherimide, polyamide, polyetheretherketone, polyamide Carbonate, polyvinyl chloride, polyacrylic acid, polymethacrylic acid, polyethyleneimine, polyvinylpyridine, polyethylene glycol, cellulose ester, polystyrene, polybutadiene, polyphenylene ether, polyurethane, bromine One or a mixture of polyphenylene ether and polyvinyl alcohol. 7.如权利要求1所述模板法制备多孔聚合物微针的方法，其特征在于，所述步骤(1)得到的所述聚合物溶液中，所述聚合物与所述模板剂两者的质量比为19:1–1:19；所述模板剂优选为颗粒状粉末，颗粒的粒径为2–50000nm；7. The method for preparing porous polymer microneedles by a template method according to claim 1, wherein in the polymer solution obtained in the step (1), the difference between the polymer and the template agent is The mass ratio is 19:1-1:19; the template agent is preferably a granular powder, and the particle size of the particles is 2-50000nm; 优选的，所述模板剂直径为5μm，该模板剂与所述聚合物两者的质量比为3:2，所述步骤(4)相应得到的所述多孔聚合物微针其孔径大小为4.8μm，孔隙率为50％；或者，所述模板剂直径为10μm，模板剂与聚合物质量比为5:1，所述步骤(4)相应得到的所述多孔聚合物微针其孔径大小为9.7μm，孔隙率为83％。Preferably, the diameter of the template is 5 μm, the mass ratio between the template and the polymer is 3:2, and the porous polymer microneedles obtained in step (4) have a pore size of 4.8 μm, the porosity is 50%; or, the diameter of the template agent is 10 μm, the mass ratio of the template agent to the polymer is 5:1, and the corresponding porous polymer microneedles obtained in the step (4) have a pore size of 9.7 μm with a porosity of 83%. 8.如权利要求1所述模板法制备多孔聚合物微针的方法，其特征在于，所述步骤(2)具体是采用离心、抽真空、超声、加热、振荡中的一种方法或几种方法联用以将所述聚合物溶液填入微针模具中；8. The method for preparing porous polymer microneedles by template method according to claim 1, wherein the step (2) is to adopt one or more methods of centrifugation, vacuuming, ultrasonication, heating, and vibration. a combination of methods for filling the polymer solution into a microneedle mold; 所述步骤(3)具体是采用冻干、烘干、晾干、气体吹干、超临界流体萃取中的一种方法或多种方法联用以除去所述溶剂A。In the step (3), one or more methods of freeze-drying, drying, air-drying, gas drying, and supercritical fluid extraction are used in combination to remove the solvent A. 9.利用如权利要求1-8任意一项所述模板法制备多孔聚合物微针的方法制备得到的多孔聚合物微针的应用，其特征在于，具体是应用于制备用于提取组织液或血液的制剂，或制备具有美白美容成分、抗皱美容成分、除皱美容成分、祛斑美容成分、保湿美容成分、抗生素、小分子药物、蛋白类药物或中药复方药物的经皮给药制剂，或制备用于治疗糖尿病、银屑病、脱发或浅表皮肤瘤疾病的经皮给药的药物制剂。9. The application of the porous polymer microneedle prepared by the method for preparing the porous polymer microneedle by the template method according to any one of claims 1 to 8, characterized in that, it is specifically applied to the preparation for extracting tissue fluid or blood preparations, or preparations for transdermal administration with whitening cosmetic ingredients, anti-wrinkle cosmetic ingredients, wrinkle-removing cosmetic ingredients, freckle cosmetic ingredients, moisturizing cosmetic ingredients, antibiotics, small molecule drugs, protein drugs or traditional Chinese medicine compound drugs, or preparations for Pharmaceutical formulations for transdermal administration for the treatment of diabetes, psoriasis, alopecia or superficial skin neoplasia.
CN201811104132.3A 2018-09-21 2018-09-21 Method for preparing porous polymer microneedles by template method and its application Pending CN109364366A (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
CN201811104132.3A CN109364366A (en) 2018-09-21 2018-09-21 Method for preparing porous polymer microneedles by template method and its application

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
CN201811104132.3A CN109364366A (en) 2018-09-21 2018-09-21 Method for preparing porous polymer microneedles by template method and its application

Publications (1)

Publication Number Publication Date
CN109364366A true CN109364366A (en) 2019-02-22

Family

ID=65402191

Family Applications (1)

Application Number Title Priority Date Filing Date
CN201811104132.3A Pending CN109364366A (en) 2018-09-21 2018-09-21 Method for preparing porous polymer microneedles by template method and its application

Country Status (1)

Country Link
CN (1) CN109364366A (en)

Cited By (19)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN110664439A (en) * 2019-09-05 2020-01-10 华中科技大学 Microneedle capable of extracting skin tissue fluid and preparation method thereof
CN110812687A (en) * 2019-11-18 2020-02-21 山东君合春医药科技有限公司 Preparation method of porous polymer microneedle
CN110854441A (en) * 2019-11-27 2020-02-28 山东大学 Three-dimensional porous current collector, template etching method and application
CN111765911A (en) * 2019-04-02 2020-10-13 天津大学 Ozone/UV radiation-treated silver nanowire-embedded PDMS-based capacitive sensor
CN111765908A (en) * 2019-04-02 2020-10-13 天津大学 Method for fabricating silver nanowires embedded in PDMS flexible capacitive sensor based on template method
CN111765909A (en) * 2019-04-02 2020-10-13 天津大学 Method for fabricating flexible capacitive sensor based on polycarbonate template method
CN111765910A (en) * 2019-04-02 2020-10-13 天津大学 Flexible capacitive sensors with silver nanowires embedded in PDMS
CN111825880A (en) * 2020-07-30 2020-10-27 河南农业大学 A high frequency response porous PEDOT:PSS thin film material and its preparation method and application
CN112321870A (en) * 2020-11-06 2021-02-05 浙江工商大学 A kind of microneedle patch and its preparation method and application
CN112842333A (en) * 2020-12-31 2021-05-28 华中科技大学 Visual glucose concentration detection microneedle patch, preparation method and application
CN113289876A (en) * 2021-04-30 2021-08-24 重庆大学 Preparation method of metal protective film with self-repairing function and super-amphiphobic function
CN113440474A (en) * 2021-07-29 2021-09-28 东南大学 High-drug-loading high-flexibility porous microneedle material and preparation method thereof
CN113797155A (en) * 2021-09-14 2021-12-17 中国科学院理化技术研究所 A kind of insoluble transdermal microneedle patch and preparation method and application thereof
CN114129503A (en) * 2021-11-19 2022-03-04 烟台魔技纳米科技有限公司 Preparation method of porous microneedle with adjustable pore size
CN114558116A (en) * 2022-03-09 2022-05-31 西安交通大学 Microneedle with accurate controllable pulse type drug release function and preparation method
WO2022148114A1 (en) * 2021-01-08 2022-07-14 中山大学 Sensor for detecting plant active small molecules and manufacturing method
CN114767618A (en) * 2022-05-17 2022-07-22 南京鼓楼医院 Inverse opal structure microneedle array with structural color and preparation method and application thereof
CN116410517A (en) * 2023-05-31 2023-07-11 河南工业大学 A preparation method of dielectric material for triboelectric nanogenerator
KR20230130408A (en) * 2022-03-03 2023-09-12 주식회사 엘지생활건강 Solid microneedle comprising drug and method for manufacturing same

Citations (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1269247A (en) * 2000-04-14 2000-10-11 清华大学 Manufacture of porous holder for repairing tissue and organ
US20020082543A1 (en) * 2000-12-14 2002-06-27 Jung-Hwan Park Microneedle devices and production thereof
CN1864976A (en) * 2006-04-06 2006-11-22 上海交通大学 Microneedle preparation method based on multiplayer processing technology
CN101227940A (en) * 2005-07-25 2008-07-23 纳米技术维多利亚有限公司 Microarray device
CN105581975A (en) * 2014-11-10 2016-05-18 （株）设模磊 Micro-needle and micro-needle patch
CN106362223A (en) * 2016-08-26 2017-02-01 南通纺织丝绸产业技术研究院 Porous silk fibroin microneedle administration device and preparation method thereof
CN108325064A (en) * 2018-03-02 2018-07-27 莆田学院 A kind of sustained release micropin and preparation method thereof

Patent Citations (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1269247A (en) * 2000-04-14 2000-10-11 清华大学 Manufacture of porous holder for repairing tissue and organ
US20020082543A1 (en) * 2000-12-14 2002-06-27 Jung-Hwan Park Microneedle devices and production thereof
CN101227940A (en) * 2005-07-25 2008-07-23 纳米技术维多利亚有限公司 Microarray device
CN1864976A (en) * 2006-04-06 2006-11-22 上海交通大学 Microneedle preparation method based on multiplayer processing technology
CN105581975A (en) * 2014-11-10 2016-05-18 （株）设模磊 Micro-needle and micro-needle patch
CN106362223A (en) * 2016-08-26 2017-02-01 南通纺织丝绸产业技术研究院 Porous silk fibroin microneedle administration device and preparation method thereof
CN108325064A (en) * 2018-03-02 2018-07-27 莆田学院 A kind of sustained release micropin and preparation method thereof

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
LIMING LIU,HIROYUKI KAI,KUNIAKI NAGAMINE,YUDAI OGAWA AND MAT: "Porous polymer microneedles with interconnecting microchannels for rapid fluid transport", 《RSC ADVANCES》 *

Cited By (27)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN111765910A (en) * 2019-04-02 2020-10-13 天津大学 Flexible capacitive sensors with silver nanowires embedded in PDMS
CN111765908A (en) * 2019-04-02 2020-10-13 天津大学 Method for fabricating silver nanowires embedded in PDMS flexible capacitive sensor based on template method
CN111765909A (en) * 2019-04-02 2020-10-13 天津大学 Method for fabricating flexible capacitive sensor based on polycarbonate template method
CN111765911A (en) * 2019-04-02 2020-10-13 天津大学 Ozone/UV radiation-treated silver nanowire-embedded PDMS-based capacitive sensor
CN110664439A (en) * 2019-09-05 2020-01-10 华中科技大学 Microneedle capable of extracting skin tissue fluid and preparation method thereof
CN110812687A (en) * 2019-11-18 2020-02-21 山东君合春医药科技有限公司 Preparation method of porous polymer microneedle
CN110854441A (en) * 2019-11-27 2020-02-28 山东大学 Three-dimensional porous current collector, template etching method and application
CN110854441B (en) * 2019-11-27 2020-12-22 山东大学 A three-dimensional porous current collector and template etching method and application
CN111825880A (en) * 2020-07-30 2020-10-27 河南农业大学 A high frequency response porous PEDOT:PSS thin film material and its preparation method and application
CN112321870A (en) * 2020-11-06 2021-02-05 浙江工商大学 A kind of microneedle patch and its preparation method and application
CN112321870B (en) * 2020-11-06 2022-11-18 浙江工商大学 A kind of microneedle patch and its preparation method and application
CN112842333A (en) * 2020-12-31 2021-05-28 华中科技大学 Visual glucose concentration detection microneedle patch, preparation method and application
WO2022148114A1 (en) * 2021-01-08 2022-07-14 中山大学 Sensor for detecting plant active small molecules and manufacturing method
CN113289876A (en) * 2021-04-30 2021-08-24 重庆大学 Preparation method of metal protective film with self-repairing function and super-amphiphobic function
CN113440474A (en) * 2021-07-29 2021-09-28 东南大学 High-drug-loading high-flexibility porous microneedle material and preparation method thereof
CN113440474B (en) * 2021-07-29 2022-07-12 东南大学 A kind of porous microneedle material with high drug loading and high flexibility and preparation method thereof
CN113797155A (en) * 2021-09-14 2021-12-17 中国科学院理化技术研究所 A kind of insoluble transdermal microneedle patch and preparation method and application thereof
WO2023040568A1 (en) * 2021-09-14 2023-03-23 中国科学院理化技术研究所 Insoluble transdermal microneedle patch, preparation method therefor and application thereof
JP7529914B2 (en) 2021-09-14 2024-08-06 中国科学院理化技術研究所 Insoluble transdermal microneedle patch and its preparation method and application
CN114129503A (en) * 2021-11-19 2022-03-04 烟台魔技纳米科技有限公司 Preparation method of porous microneedle with adjustable pore size
KR20230130408A (en) * 2022-03-03 2023-09-12 주식회사 엘지생활건강 Solid microneedle comprising drug and method for manufacturing same
KR102782194B1 (en) * 2022-03-03 2025-03-13 주식회사 엘지생활건강 Solid microneedle comprising drug and method for manufacturing same
CN114558116A (en) * 2022-03-09 2022-05-31 西安交通大学 Microneedle with accurate controllable pulse type drug release function and preparation method
CN114767618A (en) * 2022-05-17 2022-07-22 南京鼓楼医院 Inverse opal structure microneedle array with structural color and preparation method and application thereof
CN114767618B (en) * 2022-05-17 2023-02-24 南京鼓楼医院 Inverse opal structure microneedle array with structural color and preparation method and application thereof
CN116410517A (en) * 2023-05-31 2023-07-11 河南工业大学 A preparation method of dielectric material for triboelectric nanogenerator
CN116410517B (en) * 2023-05-31 2025-05-02 河南工业大学 Preparation method of dielectric material for friction nano generator

Similar Documents

Publication Publication Date Title
CN109364366A (en) Method for preparing porous polymer microneedles by template method and its application
CN110115707B (en) A method for preparing porous polymer microneedles based on phase separation technology and its application
CN110840822B (en) Method for preparing porous polymer microneedle and application thereof
Takeuchi et al. Flexible and porous microneedles of PDMS for continuous glucose monitoring
Madden et al. Biosensing in dermal interstitial fluid using microneedle based electrochemical devices
CN104888284B (en) Hollow fibroin albumen micropin delivery system of swelling type and preparation method thereof
CN204767021U (en) Hollow silk fibroin microneedle structure
CN110664439B (en) Microneedle capable of extracting skin tissue fluid and preparation method thereof
JP5063544B2 (en) Transdermal absorption sheet and method for producing the same
CN108785244B (en) Hydrophobic drug-loaded soluble microneedle and preparation method thereof
US20200061358A1 (en) Microneedle with porous coating layer, manufacturing method thereof and microneedle patch with the same
JP2011224332A (en) Skin absorption sheet and method for manufacturing the same
CN106362223B (en) Porous fibroin albumen micropin drug delivery device and preparation method thereof
He et al. Advances in porous microneedle systems for drug delivery and biomarker detection: A mini review
CN115920222B (en) Microneedle and preparation method thereof, microneedle patch and preparation method thereof
CN113288882A (en) Rapid separation microneedle patch and preparation method thereof
WO2016155082A1 (en) Swelling silk fibroin microneedle drug delivery system and preparation method thereof
CN114767618B (en) Inverse opal structure microneedle array with structural color and preparation method and application thereof
CN109674737A (en) A kind of rapidly dissolvable micropin and its preparation and application based on soluble small molecular
Zhao et al. In vivo monitoring of microneedle-based transdermal drug delivery of insulin
Kochhar et al. Microneedles for transdermal drug delivery
CN117100682A (en) Hollow sponge bone needle and preparation method and application thereof
Zhao et al. Bamboo-inspired gasotransmitter microfibres for wound healing
CN105434332A (en) Preparation method for water-soluble biological macromolecular microneedle membrane
Yuan et al. State-of-the-art Review of Metallic Microneedles: Structure, Fabrication, and Application

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: 20190222

点击 这是indexloc提供的php浏览器服务，不要输入任何密码和下载