CN108245481A - Microneedle and microneedle patch - Google Patents

Microneedle and microneedle patch Download PDF

Info

Publication number
CN108245481A
CN108245481A CN201810030840.0A CN201810030840A CN108245481A CN 108245481 A CN108245481 A CN 108245481A CN 201810030840 A CN201810030840 A CN 201810030840A CN 108245481 A CN108245481 A CN 108245481A
Authority
CN
China
Prior art keywords
micropin
glucan
microneedle
matrix
mold
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
CN201810030840.0A
Other languages
Chinese (zh)
Inventor
姜岷
古蕾
方艳
马江锋
信丰学
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.)
Nanjing Tech University
Original Assignee
Nanjing Tech University
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 Nanjing Tech University filed Critical Nanjing Tech University
Priority to CN201810030840.0A priority Critical patent/CN108245481A/en
Publication of CN108245481A publication Critical patent/CN108245481A/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
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/045—Hydroxy compounds, e.g. alcohols; Salts thereof, e.g. alcoholates
    • A61K31/05—Phenols
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
    • A61K31/35—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom
    • A61K31/352—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom condensed with carbocyclic rings, e.g. methantheline 
    • A61K31/353—3,4-Dihydrobenzopyrans, e.g. chroman, catechin
    • A61K31/355—Tocopherols, e.g. vitamin E
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/496—Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/535—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one oxygen as the ring hetero atoms, e.g. 1,2-oxazines
    • A61K31/5375—1,4-Oxazines, e.g. morpholine
    • A61K31/5383—1,4-Oxazines, e.g. morpholine ortho- or peri-condensed with heterocyclic ring systems
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/60—Salicylic acid; Derivatives thereof
    • A61K31/612—Salicylic acid; Derivatives thereof having the hydroxy group in position 2 esterified, e.g. salicylsulfuric acid
    • A61K31/616—Salicylic acid; Derivatives thereof having the hydroxy group in position 2 esterified, e.g. salicylsulfuric acid by carboxylic acids, e.g. acetylsalicylic acid
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/26—Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
    • A61K47/36—Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/02—Cosmetics or similar toiletry preparations characterised by special physical form
    • A61K8/0204—Specific forms not provided for by any of groups A61K8/0208 - A61K8/14
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/60—Sugars; Derivatives thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/72—Cosmetics or similar toiletry preparations characterised by the composition containing organic macromolecular compounds
    • A61K8/73—Polysaccharides
    • 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
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q19/00—Preparations for care of the skin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2800/00—Properties of cosmetic compositions or active ingredients thereof or formulation aids used therein and process related aspects
    • A61K2800/80—Process related aspects concerning the preparation of the cosmetic composition or the storage or application thereof
    • A61K2800/91—Injection
    • 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
    • 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)
  • Veterinary Medicine (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Epidemiology (AREA)
  • Chemical & Material Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Medicinal Chemistry (AREA)
  • Dermatology (AREA)
  • Engineering & Computer Science (AREA)
  • Birds (AREA)
  • Medical Informatics (AREA)
  • Anesthesiology (AREA)
  • Biomedical Technology (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Hematology (AREA)
  • Molecular Biology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Oil, Petroleum & Natural Gas (AREA)
  • Biochemistry (AREA)
  • Inorganic Chemistry (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicinal Preparation (AREA)

Abstract

The invention relates to a microneedle and a microneedle patch, wherein the microneedle comprises a microneedle-shaped substrate and an active ingredient embedded in the substrate, the substrate is hydrogel formed by polymerization of glucan and tannic acid, the active ingredient is a substance with medical or cosmetic efficacy, and when the patch is applied to skin, the microneedle can be inserted into the skin by means of short-time pressing of a thumb to provide sustained release of the therapeutic active ingredient. The microneedle and microneedle patch of the present invention can effectively deliver a pharmacologically active substance through the skin without high skill or pain. The glucan and tannin polymer are of a network structure, so that the hardness and the toughness are stronger, and the prepared microneedle is not easy to break and is easier to penetrate through the stratum corneum of the skin.

Description

Micropin and microneedle patch
Technical field
The present invention relates to micropins, in more detail, are related to the poisonless biological degradable of biological source having bio-compatible Property glucan for pharmacy, medicine or beauty functions active material percutaneous dosing micropin and microneedle patch.
Background technology
Common administering mode mainly has oral medication and drug administration by injection.Oral medication is one kind of most convenient to prescription Formula, but due to hydrolases certain in stomach and liver first-pass metabolism, therapeutic effect cannot be reached for some protein drugs.Note Penetrating administration needs the doctor of high degree of skill professional technique, and pain is dangerous, and can generate sharp clinical waste.
Percutaneous dosing (transdermal drug delivery) is in recent years by a kind of administering mode attracted attention.Profit It is limited to tens of or hundreds of microns microneedle devices across the skin of main barrier layer transmitted as percutaneous medicine by the use of diameter and height Cuticula, formed through fur portion many microchannels, by these microchannels, an adequate amount of drug reach epidermis or Skin corium, later drug absorbed by blood vessel and lymph gland.It can utilize the administering mode of Noninvasive, allow drug or epidemic disease Seedling absorbs to play drug effect by skin.Hydrolytic enzyme activities are relatively low in skin, can be to avoid albumen and the inactivation of more amine drugs.
As other application, above-mentioned multiple micropins are also used for cosmetic purpose.Such as above-mentioned beauty physiology is coated on micropin After active material, transdermal transfer is carried out in the multiple microchannels formed in skin by using above-mentioned multiple micropins.
For above-mentioned micropin by being made after dextran modification, glucan is to produce endocellular enzyme through clasmatosis by recombination bacillus coli Catalysing sucrose generates the enzyme solution obtained afterwards again, and the glucan of biological source has nontoxic, good biocompatibility and biology can Degradability will not cause biological tissue's body immune response, be a kind of ideal micropin and the raw material of microneedle patch.Glucan polymerize After object micropin is degraded in skin layer living, the active constituent is gradually discharged.
However, when micropin and microneedle patch are used in particular for transmitting medicating active ingredients or vaccine activity ingredient, how to control The carrying amount of medicating active ingredients or vaccine activity ingredient processed just becomes quite important.Moreover, although glucan has good life Object compatibility and biodegradability, but since its hardness and toughness are inadequate, the material as micropin uses, usually easy to break It is disconnected, it is not easy to be pierced into skin.And how to effectively control the carrying amount of microneedle patch traditional Chinese medicine active constituent or vaccine activity ingredient It is also a problem, existing process still has improved necessity.
In addition, in the prior art, often using N, N- methylene acrylamide, cumyl peroxide etc. as crosslinking Agent, and such chemical substance cannot degrade in human body, and cell is harmful to.
Invention content
The purpose of the present invention is to provide a kind of micropin and microneedle patch based on glucan and tannin polyalcohol hydrogel, Pharmacy or beauty object can be effectively performed in the case of the skilled not generation feeling of pain of no height in the micropin and microneedle patch The transdermal transfer of matter, it is easy to use, also, glucan and tannin polymer phase ratio, in glucan, hardness and toughness are all stronger, Made micropin is not easily broken, it is easier to penetrate keratoderma.
To achieve the aforementioned purpose, the present invention provides a kind of micropin, and the micropin includes the matrix of micropin shape and is embedded in Active constituent in matrix, the hydrogel that the matrix is polymerized for glucan and tannic acid, the active constituent be with Medical treatment or the substance of beauty functions.
The structure of tannic acid isTannic acid is that a kind of plant carries Take object, it may have biocompatibility and biodegradability, glucan and tannin polymer are network structure, are had stronger hard Degree and toughness, enable micropin to penetrate keratoderma and be not easily broken.
Preferably, the active constituent is small-molecule drug, protein, peptide, gene, antibody, anesthetic, insulin, epidemic disease Seedling, polysaccharide or Cosmetic Ingredient.
Preferably, the small-molecule drug is Ciprofloxacin, aspirin, lavo-ofloxacin or Norfloxacin.
Preferably, each glucose residue of the glucan contains there are three hydroxyl, and molecular formula is
Preferably, the glucan is generated by bacterium producing enzyme catalysing sucrose.
Preferably, the glucan is that the enzyme solution obtained after clasmatosis by recombination bacillus coli production endocellular enzyme is urged again Change what sucrose generated.
Preferably, the dextran molecule amount is more than or equal to 5000.
The micropin shape matrix, the pin density on surface is 2~100/cm2。
Preferably, the micropin shape matrix, the width of the needle on surface are 20 μm~1000 μm, highly for 20 μm~ 1000μm。
Preferably, also include antioxidant in the matrix.
Preferably, the antioxidant is one kind in butylated hydroxytoluene, butylated hydroxyanisole (BHA) or alpha-tocopherol It is or a variety of.
Preferably, mass fraction of the antioxidant in the drying tip of the micropin is less than or equal to 3%.
Preferably, mass fraction of the antioxidant in the drying tip of the micropin is 0.03~2%.
The present invention also provides a kind of microneedle patch based on above-mentioned micropin, the microneedle patch includes substrate and is formed in The micropin on substrate.
The soluble glucan formed is catalyzed by sucrose has larger viscosity in itself, can replace chemical adhesive will be micro- Needle is bonded together with aeration hospital gauze substrate by low temperature cold rolling.
When patch is spread on skin, by the short depression of thumb, institute is provided after can micropin be inserted into skin State the sustained release of therapeutic activity ingredient.
The present invention also provides a kind of production methods of above-mentioned micropin, include the following steps：
(1) glucan is configured to the aqueous solution of final concentration of 10~30g/L, backward glucan aqueous solution in add in Tannic acid so that final concentration of 2~5g/L of tannic acid in 20~25 DEG C of 20~60min of hybrid reaction, obtains matrix solution；
(2) add in active constituent into the matrix solution so that the mass fraction of the active constituent for 30%~ 65%；
(3) matrix solution is coated on to the mold with the chamber array for being molded micropin；
(4) after the mold for being coated with matrix solution being dried, by the micropin of drying and moulding and the mold point From.
Preferably, the preparation method of step (3) described mold includes the following steps：
(3-1) prepares the metal positive for including multiple tapered protrusions；
(3-2) by above-mentioned metal positive be pressed on molding dimethyl silicone polymer (polydimethylsiloxane, PDMS) the flat surface of module so that the tapered protrusion is pierced into the dimethyl silicone polymer, and it is recessed with taper to form surface Sunken dimethyl silicone polymer former, the former are the mold.The dimethyl silicone polymer module can be appointed Solid of the meaning with flat surface is blocky.
Preferably, the drying temperature described in step (4) is 55~60 DEG C.
The beneficial effects of the present invention are：
The micropin and microneedle patch of the present invention, in the case of the skilled or pain of no height, can be effectively performed pharmacology The transdermal transfer of active material.Glucan and tannin polymer are network structure, have stronger hardness and toughness, made Micropin is not easily broken, it is easier to penetrate keratoderma.
Description of the drawings
Fig. 1 is the schematic diagram of matrix structure of the present invention.
Fig. 2 is the preparation method process schematic of the embodiment of the present invention 2, wherein 1 is metal positive, 2 be PDMS molds, 3 It is the hydrogel matrix.
Fig. 3 is the sectional view of the microneedle patch.Stain represents the active constituent in figure.
Fig. 4 is the signal that microneedle patch discharges the effective active factor by pressing through keratoderma and in the dermis Figure.
Specific embodiment
Embodiment 1
(1) the ultrapure water dissolution drying of deionization and the extremely final concentration of 30g/ of glucan powder (molecular weight 5000) after purification L adds in tannic acid powder to final concentration of 2g/L, and quick mixing on vortex mixer reacts 20min in 20 DEG C, obtains matrix Solution.
(2) Ciprofloxacin is added in into the matrix solution so that the mass fraction of Ciprofloxacin is 30%.
(3) mixed liquor for obtaining step (2) injects the small of PDMS molds with syringe or capillary dispenser rapidly In recess.Recess on PDMS molds is taper, and density is 100/cm2, the width being each recessed is 20 μm, and depth is 100μm。
(4) mold is integrally put into baking oven, it is 4 hours dry in 60 DEG C.
(5) gently molding micropin is taken out from the fine pits of mold.
Embodiment 2
Prepare PDMS molds with the following method first：
The stainless steel formpiston comprising multiple tapered protrusions is prepared first, and the density of tapered protrusion is 2/cm2, each taper The width of protrusion is 200 μm (conical lower portions), and depth is 20 μm.Stainless steel formpiston is pressed on the smooth of molding PDMS squares Surface so that tapered protrusion is pierced into PDMS, forms conical indentation.The PDMS squares are PDMS molds at this time.
(1) the ultrapure water dissolution drying of deionization and the extremely final concentration of 10g/ of glucan powder (molecular weight 9000) after purification L adds in tannic acid powder to final concentration of 3g/L, and quick mixing on vortex mixer reacts 30min in 23 DEG C, obtains matrix Solution.
(2) functioning gene is added in into the matrix solution so that the mass fraction of functioning gene is 40%, is added in Butylated hydroxytoluene so that butylated hydroxytoluene accounts for the 0.01% of glucan and the total dry mass of tannic acid.
(3) mixed liquor for obtaining step (2) injects the small of PDMS molds with syringe or capillary dispenser rapidly In recess.
(4) mold is integrally put into baking oven, it is 5 hours dry in 55 DEG C.
Embodiment 3
Prepare PDMS molds with the following method first：
The stainless steel formpiston comprising multiple tapered protrusions is prepared first, and the density of tapered protrusion is 50/cm2, it is each to bore The width of shape protrusion is 1000 μm (conical lower portions), and depth is 1000 μm.Stainless steel formpiston is pressed on molding PDMS squares Flat surface so that tapered protrusion be pierced into PDMS, formed conical indentation.The PDMS squares are PDMS molds at this time.
(1) the ultrapure water dissolution of deionization is dried and glucan powder (molecular weight 10000) after purification is extremely final concentration of 20g/L adds in tannic acid powder to final concentration of 4g/L, and quick mixing on vortex mixer is reacted 60min in 25 DEG C, obtained Matrix solution.
(2) lavo-ofloxacin is added in into the matrix solution so that the mass fraction of lavo-ofloxacin is 65%, is added in Butylated hydroxyanisole (BHA) and alpha-tocopherol so that the gross mass of butylated hydroxyanisole (BHA) and alpha-tocopherol accounts for glucan and tannic acid The 0.03% of total dry mass.
(3) mixed liquor for obtaining step (2) injects the small of PDMS molds with syringe or capillary dispenser rapidly In recess.
(4) mold is integrally put into baking oven, it is 4 hours dry in 60 DEG C.
Embodiment 4
Prepare PDMS molds with the following method first：
The stainless steel formpiston comprising multiple tapered protrusions is prepared first, and the density of tapered protrusion is 70/cm2, it is each to bore The width of shape protrusion is 500 μm (conical lower portions), and depth is 500 μm.Stainless steel formpiston is pressed on molding PDMS squares Flat surface so that tapered protrusion is pierced into PDMS, forms conical indentation.The PDMS squares are PDMS molds at this time.
(1) the ultrapure water dissolution of deionization is dried and glucan powder (molecular weight 50000) after purification is extremely final concentration of 25g/L adds in tannic acid powder to final concentration of 5g/L, and quick mixing on vortex mixer is reacted 40min in 22 DEG C, obtained Matrix solution.
(2) Cosmetic Ingredient is added in into the matrix solution so that the mass fraction of Cosmetic Ingredient is 45%, adds in butyl Hydroxy-methylbenzene so that butylated hydroxytoluene quality accounts for the 1% of glucan and the total dry mass of tannic acid.
(3) mixed liquor for obtaining step (2) injects the small of PDMS molds with syringe or capillary dispenser rapidly In recess.
(4) mold is integrally put into baking oven, it is 4 hours dry in 60 DEG C.
Embodiment 5
Prepare PDMS molds with the following method first：
The stainless steel formpiston comprising multiple tapered protrusions is prepared first, and the density of tapered protrusion is 10/cm2, it is each to bore The width of shape protrusion is 10 μm (conical lower portions), and depth is 300 μm.Stainless steel formpiston is pressed on the flat of molding PDMS squares Whole surface so that tapered protrusion is pierced into PDMS, forms conical indentation.The PDMS squares are PDMS molds at this time.
(1) the ultrapure water dissolution of deionization is dried and glucan powder (molecular weight 150000) after purification is extremely final concentration of 30g/L adds in tannic acid powder to final concentration of 5g/L, and quick mixing on vortex mixer is reacted 50min in 20 DEG C, obtained Matrix solution.
(2) anesthetic is added in into the matrix solution so that the mass fraction of anesthetic is 30%, adds in butylhydroxy Toluene so that butylated hydroxytoluene quality accounts for the 0.1% of glucan and the total dry mass of tannic acid.
(3) mixed liquor for obtaining step (2) injects the small of PDMS molds with syringe or capillary dispenser rapidly In recess.
(4) mold is integrally put into baking oven, it is 4 hours dry in 60 DEG C.
Embodiment 6
Embodiment 6 is differed only in embodiment 5：
The dextran molecule amount selected in step (1) is 500000, and the active constituent that step (2) adds in is protein, Mass fraction is 50%；Step (3) butylated hydroxytoluene quality accounts for the 0.5% of glucan and the total dry mass of tannic acid.
Embodiment 7
Embodiment 7 is differed only in embodiment 5：
The dextran molecule amount selected in step (1) is 100000, and the active constituent that step (2) adds in is insulin, Mass fraction is 65%；Step (3) butylated hydroxytoluene quality accounts for the 2% of glucan and the total dry mass of tannic acid.Step (3) changes With in multiple fine pits of scraper type rubbing method coating substrate solution to mold.
Embodiment 8
Embodiment 8 is differed only in embodiment 5：
The dextran molecule amount selected in step (1) is 10000, and the active constituent that step (2) adds in is vaccine；Step (3) butylated hydroxytoluene quality accounts for the 3% of glucan and the total dry mass of tannic acid.
Embodiment 9
The preparation of microneedle patch
Before step (4) is dry, mold is applied to using finger pressure by the step of using embodiment 1 for patch substrate On surface so that micropin is adhered to substrate surface, then carries out the drying of step (4) again, gently will be by substrate after dry The micropin of type takes out from the fine pits of mold.

Claims (10)

1. a kind of micropin, which is characterized in that matrix and the active constituent being embedded in matrix, the matrix including micropin shape For the hydrogel that glucan and tannic acid are polymerized, the active constituent is the substance with medical treatment or beauty functions；It is preferred that The active constituent be small-molecule drug, protein, peptide, gene, antibody, anesthetic, insulin, vaccine, polysaccharide or U.S. Rongcheng point；The preferred small-molecule drug is Ciprofloxacin, aspirin, lavo-ofloxacin or Norfloxacin.
2. micropin according to claim 1, which is characterized in that the glucan is generated by bacterium producing enzyme catalysing sucrose； Preferably, the glucan is the enzyme solution catalysing sucrose production again obtained after clasmatosis by recombination bacillus coli production endocellular enzyme Raw.
3. micropin according to claim 1, which is characterized in that the dextran molecule amount is more than or equal to 5000.
4. micropin according to claim 1, which is characterized in that the pin density of the micropin shape stromal surface is 2 ~ 100 A/cm2, width is 20 μm ~ 1000 μm, is highly 20 μm ~ 1000 μm.
5. micropin according to claim 1, which is characterized in that also include antioxidant in the matrix；Preferably Antioxidant is one or more in butylated hydroxytoluene, butylated hydroxyanisole (BHA) or alpha-tocopherol.
6. micropin according to claim 5, which is characterized in that the antioxidant is in the drying tip of the micropin Mass fraction be less than or equal to 3%；Preferred mass fraction is 0.03 ~ 2%.
7. a kind of microneedle patch, which is characterized in that the microneedle patch includes substrate and the claim being formed on substrate Any micropins of 1-6.
8. a kind of production method of any micropins of claim 1-6, includes the following steps：
（1）Glucan is configured to the aqueous solution of final concentration of 10 ~ 30g/L, backward glucan aqueous solution in add in tannin Acid so that final concentration of 2 ~ 5g/L of tannic acid in 20 ~ 25 DEG C of 20 ~ 60min of hybrid reaction, obtains matrix solution；
（2）Active constituent is added in into the matrix solution so that the mass fraction of the active constituent is 30% ~ 65%；
（3）Matrix solution, which is coated on, has the mold of the chamber array for being molded micropin；
（4）After the mold for being coated with matrix solution is dried, by the micropin of drying and moulding and the mold separation.
9. according to the method described in claim 8, it is characterized in that, step（3）The preparation method of the mold includes following step Suddenly：
（3-1）Prepare the metal positive for including multiple tapered protrusions；
（3-2）Above-mentioned metal positive is pressed on to the flat surface of molding dimethyl silicone polymer module so that the taper Protrusion is pierced into the dimethyl silicone polymer, forms the dimethyl silicone polymer former that surface carries conical indentation, the former As described mold.
10. according to the method described in claim 8, it is characterized in that, step（4）The drying temperature is 55 ~ 60 DEG C.
CN201810030840.0A 2018-01-12 2018-01-12 Microneedle and microneedle patch Pending CN108245481A (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
CN201810030840.0A CN108245481A (en) 2018-01-12 2018-01-12 Microneedle and microneedle patch

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
CN201810030840.0A CN108245481A (en) 2018-01-12 2018-01-12 Microneedle and microneedle patch

Publications (1)

Publication Number Publication Date
CN108245481A true CN108245481A (en) 2018-07-06

Family

ID=62726943

Family Applications (1)

Application Number Title Priority Date Filing Date
CN201810030840.0A Pending CN108245481A (en) 2018-01-12 2018-01-12 Microneedle and microneedle patch

Country Status (1)

Country Link
CN (1) CN108245481A (en)

Cited By (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN108653177A (en) * 2018-07-20 2018-10-16 华中科技大学同济医学院附属协和医院 A kind of microneedle patch and preparation method thereof for whitening spot-removing
CN111991344A (en) * 2020-09-28 2020-11-27 四川大学 Microneedle patch suitable for local anesthesia and preparation method thereof
CN113543835A (en) * 2019-03-06 2021-10-22 Lts勒曼治疗系统股份公司 Microneedle array with heat generating element
CN113876948A (en) * 2021-08-18 2022-01-04 广州贝奥吉因生物科技股份有限公司 Germanium alkene two-dimensional nano-drug microneedle, preparation method thereof and microneedle patch
CN114146048A (en) * 2021-12-03 2022-03-08 上海中医药大学 Needle and medicine integrated hydrogel microneedle

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN104069484A (en) * 2014-03-28 2014-10-01 上海交通大学 Interferon microneedle, as well as preparation method and application thereof

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN104069484A (en) * 2014-03-28 2014-10-01 上海交通大学 Interferon microneedle, as well as preparation method and application thereof

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
王超: "单宁酸辅助交联对纤维素/聚丙烯酰胺透明薄膜机械性能的影响", 《2017第一届天然材料研究与应用研讨会论文集》 *

Cited By (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN108653177A (en) * 2018-07-20 2018-10-16 华中科技大学同济医学院附属协和医院 A kind of microneedle patch and preparation method thereof for whitening spot-removing
CN113543835A (en) * 2019-03-06 2021-10-22 Lts勒曼治疗系统股份公司 Microneedle array with heat generating element
CN111991344A (en) * 2020-09-28 2020-11-27 四川大学 Microneedle patch suitable for local anesthesia and preparation method thereof
CN113876948A (en) * 2021-08-18 2022-01-04 广州贝奥吉因生物科技股份有限公司 Germanium alkene two-dimensional nano-drug microneedle, preparation method thereof and microneedle patch
CN114146048A (en) * 2021-12-03 2022-03-08 上海中医药大学 Needle and medicine integrated hydrogel microneedle
CN114146048B (en) * 2021-12-03 2023-03-14 上海中医药大学 Needle and medicine integrated hydrogel microneedle
WO2023098158A1 (en) * 2021-12-03 2023-06-08 上海中医药大学 Needle-medicine integrated hydrogel microneedle

Similar Documents

Publication Publication Date Title
CN108245481A (en) Microneedle and microneedle patch
Duarah et al. Recent advances in microneedle-based drug delivery: Special emphasis on its use in paediatric population
Chen et al. Preparation, properties and challenges of the microneedles-based insulin delivery system
Jamaledin et al. Engineered microneedle patches for controlled release of active compounds: recent advances in release profile tuning
Moniz et al. Marine polymeric microneedles for transdermal drug delivery
CN109045460B (en) Microneedle patch and preparation method thereof
US20140005606A1 (en) Embeddable micro-needle patch for transdermal drug delivery and method of manufacturing the same
Chen et al. Safety evaluation of solid polymer microneedles in human volunteers at different application sites
CN111904951A (en) Microneedle patch and preparation method thereof
CN105854172A (en) Method for manufacturing microstructure body
Rajput et al. A key role by polymers in microneedle technology: a new era
JP2012254952A (en) Percutaneous absorption preparation
Pahal et al. Microneedles for extended transdermal therapeutics: a route to advanced healthcare
Mahato Microneedles in drug delivery
CN114917465B (en) Self-heating microneedle drug-loaded patch and preparation method thereof
Rai et al. Microneedle arrays for cutaneous and transcutaneous drug delivery, disease diagnosis, and cosmetic aid
Alshammari et al. An update on microneedle in insulin delivery: quality attributes, clinical status and challenges for clinical translation
Li et al. An update on microneedle-based systems for diabetes
CN105498081A (en) Sterile microstructure body and preparation method thereof
CN108969879B (en) Compound microneedle and microneedle patch
Naik et al. Drug Delivery Through Microneedles for Improved Permeability and Efficacy: Fabrication, Methodology and Applications
Sil et al. Promising role of microneedles in therapeutic and biomedical applications
Lee et al. Commercialized microneedles
CN112752590A (en) Device comprising microneedles for skin in situ reactions
Govender et al. 3D bioprinted microneedles: merging drug delivery and scaffold science for tissue-specific applications

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

Application publication date: 20180706

RJ01 Rejection of invention patent application after publication