CN105411997A - Degradable microstructure body and preparation method thereof - Google Patents
Degradable microstructure body and preparation method thereof Download PDFInfo
- Publication number
- CN105411997A CN105411997A CN201511024530.0A CN201511024530A CN105411997A CN 105411997 A CN105411997 A CN 105411997A CN 201511024530 A CN201511024530 A CN 201511024530A CN 105411997 A CN105411997 A CN 105411997A
- Authority
- CN
- China
- Prior art keywords
- micropin
- functional component
- degradable
- microstructured bodies
- gel
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0087—Galenical forms not covered by A61K9/02 - A61K9/7023
- A61K9/0097—Micromachined devices; Microelectromechanical systems [MEMS]; Devices obtained by lithographic treatment of silicon; Devices comprising chips
-
- 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
- A61K31/16—Amides, e.g. hydroxamic acids
- A61K31/165—Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide
- A61K31/167—Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide having the nitrogen of a carboxamide group directly attached to the aromatic ring, e.g. lidocaine, paracetamol
-
- 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
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/47—Quinolines; Isoquinolines
- A61K31/485—Morphinan derivatives, e.g. morphine, codeine
-
- 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
- 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
- A61K47/38—Cellulose; Derivatives thereof
-
- 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
- A61K47/42—Proteins; Polypeptides; Degradation products thereof; Derivatives thereof, e.g. albumin, gelatin or zein
-
- 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
Abstract
The invention relates to a degradable microstructure body and a preparation method thereof. The degradable microstructure body is mainly composed of a microneedle and a base where the microneedle is erected. The preparation method includes the steps that firstly, gel used for preparing the base and the microneedle is provided, and an antalgic material is added into the gel of the microneedle; secondly, a mould is provided; thirdly, injection molding is carried out; fourthly, curing and sterilizing are carried out. The microstructure body has the advantages of being long-acting in sustained release, good in experience feeling, simple in process and the like, and can be applied to the fields of biological medicine and medical cosmetology.
Description
Technical field
The present invention relates to a kind of degradable microstructured bodies and preparation method thereof, particularly relate to the biodegradable microstructured bodies be inserted in application on human skin, can be applicable to biological medicine and medical and beauty treatment fields.
Background technology
At present, oral and injection is the most frequently used administering mode of biological medicine and medical and beauty treatment fields, but oral after gastric acid not high, the drug administration by injection syringe needle Diazolidinyl Urea deep layer neurocyte of pharmaceutical efficacy easily cause suffering to human body.Someone begins one's study the biodegradable microstructured bodies that is added with functional component as the shortcoming solving above-mentioned biological medicine and the above-mentioned administration of medical and beauty treatment fields in recent years.Biological microstructured bodies thrusts in skin and functional component is supplied experimenter, and the microstructured bodies part of thrusting can be dissolved subcutaneous or be biodegradable thus disappear.It has several advantage: do not produce severe pain or hemorrhage, and rapid closing is hindered in puncture, is thus suitable for the method as subcutaneously supplying active ingredient.
The invention of more existing biological microstructured bodies at present, such as publication number is that CN201180061175.8 patent discloses primarily of the scheme of fibroin albumen as the microstructured bodies of raw material, application number be CN201210057409.8 patent discloses a kind of polymer micro needle array chip, application number be CN201380034546.2 patent describes the applicator comprising cosmetic composition microneedle array be inserted in application on human skin, application number is that CN201180067944.5 and CN201380025634.6 each provides micropin manufacture method, application number is that the patent of CN201410684523.2 provides a kind of sericin micropin for drug conveying and preparation method thereof.There is following technical problem in technology disclosed in these: produces analgesia when microstructured bodies inserts skin, cause bad experience sense to user, and meanwhile, microstructured bodies degraded is very fast, the effect that cannot reach long-acting slow-release.
Summary of the invention
How to solve above technology and become the key issue that the present invention will solve.The invention provides that experience sense is excellent, the degradable microstructured bodies of long-acting slow-release and preparation method thereof.
The micropin of microstructured bodies is inserted in skin, by the dissolving of micropin, expand or fracture and the micropin of microstructured bodies stayed skin histology inside, insert the micropin of skin to dissolve gradually in skin histology, and medicine in micropin or cosmetic composition slow releasing play corresponding efficacy effect.
The invention provides degradable microstructured bodies, the substrate (2) of standing thereon primarily of micropin (1) and micropin forms (see accompanying drawing 1).The micropin of degradable microstructured bodies provided by the invention can be circular cone or polygonal pyramid (such as triangle cone, tetragon cone, hexagon cone and octagon cone), and recommendation is circular cone.Micropin length is 0.2-2.5mm, can be 0.3-2mm or 0.35-1.5mm, also can be 0.4-1mm, optimal choice 0.5-0.8mm.Micropin centre-to-centre spacing is 0.2-2.5mm, can be 0.3-2mm or 0.35-1.5mm, also can be 0.4-1mm, optimal choice 0.5-0.8mm.Micropin tip diameter is 1-120 μm, can be 5-100 μm or 10-80 μm, optimal choice 20-50 μm.The diameter of micropin is 1-300 μm, can be 10-250 μm or 20-200 μm, also can be 30-180 μm or 50-150 μm, optimal choice 80-120 μm.Target part accounts for the 20%-90% of whole micropin length, can be 30%-80% or 40%-70%, optimal choice 50%-60%.
In order to weaken or eliminate the pain of user when microstructured bodies inserts, it is generally the micropin reducing microstructured bodies resistance and take to reduce micropin diameter when inserting skin.But reduce micropin diameter and mean that the micropin inserting skin can reduce, this can accelerate the degradation rate of micropin, and then reduces the long-acting slow-release effect of micropin.The present invention not only ensure that the long-acting slow-release effect of micropin, can also improve the experience sense of microstructured bodies while not reducing micropin diameter, micropin is added with analgesia material: morphine, bupivacaine, lignocaine, carticaine, cocaine, cincaine, cinchocaine, etidocaine, prilocaine, tetracaine, benzocaine, butacaine, oxybuprocaine, procaine, fexicaine, tricaine wherein one or more.Certainly, also have a kind of solution route to be exactly that before use, surface scribbles analgesia material, also can reduce the sense of discomfort caused when micropin inserts skin.The concentration range of analgesia material is 0.001%-20% (W/W) or 0.01%-15% (W/W), can also be 0.02%-10% (W/W) or 0.03%-8% (W/W), also can be 0.05%-5% (W/W) or 0.1%-3% (W/W), can be preferably 0.2%-2% (W/W) or 0.3%-1.5% (W/W), it is recommended that 0.5%-1% (W/W).
The Biodegradable material preparing microstructured bodies comprises one or more following materials: carboxymethyl starch, starch sulphate, poly-carboxymethyl cellulose, hydroxypropyl emthylcellulose, microcrystalline Cellulose, pregelatinized Starch, carboxymethyl cellulose, ethylhydroxyethylcellulose, cellulose acetate-phthalate, methylcellulose, carboxy-propyl cellulose, hydroxy alkyl cellulose, alkylcellulose, polyvinylpyrrolidone, polylactic acid, polyvinyl alcohol, polyacrylamide polymer, polydimethylsiloxane, chondroitin sulfate, poly lactic-co-glycolic acid, dextrin, polrvinyl chloride, chitosan, xanthan gum, dextran, polyglutamic acid, fibroin, hyaluronic acid, collagen protein, gelatin, oligopeptide.We know, the micropin part that the micropin part of microstructured bodies especially inserts skin is only the key playing efficacy effect, reach long-acting slow-release, and other parts are assosting effects.The degradation rate of Biodegradable material can change its molecular weight to realize, and solves often through crosslinked mode.In order to improve the long-acting slow-release effect of micropin, micropin of the present invention is the cross-linked derivant of Biodegradable material, especially the micropin part inserting skin is wherein one or more combinations of the cross-linking products of Biodegradable material, also can be the derivant of Biodegradable material and noncrosslinking combination.
In actual applications, be often added with in micropin as medicine or cosmetic composition, reach the object of administration.At biological medicine and medical field, as one or more combinations that the material of ingredient can be in vaccine, hormone, genetically engineered drug, polypeptide, polysaccharide, ucleosides, protein-based, chemicals, natural drug, nutritional labeling, ucleosides comprises nucleoside and nucleotide medicine.The medicine added can be following one of them or combination: antidiabetic, aspirin, angiogenic agent, antidepressant, antiinflammatory, Bu Tuofeinuo, calcitonin and analog, hydryllin, COX-II inhibitor, follicle-stimulating hormone, dermatosis treating medicine, dopamine agonist and antagonist, immunosuppressant, enkephalin and other opioid peptide, erythropoietin and analog, epidermal growth factor, glucagon, growth hormone and analog (comprising growth hormone releasing hormone), lutropin, growth hormone antagonist, heparin, hirudin and hirudin analog are as HIRULOG, anticarcinogen, IgE inhibitor and other protein inhibitor, insulin, pancreotropic hormone and analog, interferon, interleukin, luteinizing hormone releasing hormone and analog, monoclonal or polyclonal antibody, motion sickness products, muscle relaxant, opioid analgesics, anticarcinogen, nicotine, NSAID (non-steroidal anti-inflammatory drug), oligosaccharide, parathyroid hormone and analog, pth antagonist, prostaglandin antagonists, prostaglandin, scopolamine, tranquilizer, combination of serotonin agonist and antagonist, sexual hypofunction, tissue plasminogen activator, tranquillizer, there is or not have the vaccine of carrier/adjuvant, vasodilation, Main Diagnosis is as tuberculin and other allergic agent.Vaccine comprises and can bring out for human antigen or from the antigen of the immunne response of the antigen of other viral pathogen or antigen composition, can be influenza vaccines, cholera vaccine, poliomyelitis vaccine, DPT vaccine, Measles Vaccine, vaccine of epidemic menigitis, Vaccinum Encephalitidis Epidemicae, hepatitis A vaccine, Hepatitis B virus vaccine, pneumovax, hepatitis C vaccine, chickenpox vaccine, leprosy cheek vaccine, rabies vaccine, bronchitis vaccine, antityphoid vaccine, shigella vaccine, vaccine for cervical cancer, cholera vaccine, AIDS vaccine, H1N1 vaccine etc.Pharmaceutical grade protein can be the protein-based active substances such as interferon (containing natural interferon and genetic engineering interferon), insulin, immunoglobulin (such as, IgG, IgM, IgA, IgE), TNF-α, antiviral drugs.Nucleotide medicine can be plasmid, siRNA, RNAi, active small molecular DNA, nucleotide cancer therapy drug, vaccine etc.Medicine can be made by genetic engineering, also can be natural extract or chemosynthesis.
At beauty treatment fields, as wherein one or more compositions below can the comprising of cosmetic industry composition: white-skinned face function composition, moisture-keeping efficacy composition, anti-ageing functional component, acne-removing composition, acne removing scar functional component, remove red blood streak functional component, light scar functional component, remove freckle functional component, skin care functional component, treatment chloasma functional component, sun-proof function composition, moisten functional component, lock water functional component, wrinkle removing functional component, anti-inflammatory effect composition, antiallergic functional component, toxin expelling functional component, blood circulation promote composition.Whitening composition can be SymWhite377, vitamin C and derivant thereof or other whitening compositions, such as ascorbic acid glucoside, ascorbyl palmitate, BV-OSC-tetrahexyldecyl ascorbate, sodium ascorbyl phosphate disodium hydrogen, ascorbic acid glucoside, other whitening composition is Trametes, Radix Glycyrrhizae extract, aspergillus, resveratrol and derivant resveratrol phosphate, Exophiala, resveratrol Acetyl-ferulic acid ester, yeast extract, Semen Vitis viniferae extract, oxidized resveratrol, kojic acid, ellagic acid, chamenol, soybean extract, Scutellaria baicalensis extract, enoxolone, Fructus Mori extract, prestige spectrum Flos lupuli (Flos Humuli Lupuli), molasses, ferulic acid and its derivant, tetrahydrocurcumin, α (β)-arbutin, Punica granatum L., resorcinol and Trenaxmine etc.Crease-resistant composition can be retinol, TGF-β, tretinoin, retinyl acetate, thioctic acid, vitamin A palmitate etc.High molecular cosmetic composition can be biologically active peptide and its derivant, nucleic acid, oligonucleotide, various antigen, antibacterial, viral fragment, biologically active peptide and its derivant can be calcitonins, beta-endorphin, EGF, oxytocin, hPTH (1 → 34), glucagon, parathormone (PTH), insulin, amicine, thyroliberin, glutathion peroxidase, G-CSF, secretin, angiotensin, gastrin, enkephalin, neurotensin, somatomedin, growth hormone, luteinising hormone-releasing hormo, Substance P, Endothelin, interferon, white atrial natriuretic peptide, vasopressin, growth hormone releasing hormone, superoxide dismutase, Desmopressin, Kallidin I, dynorphin, thyrotropin, prolactin antagonist, be situated between element, intacellin and their salt etc.Antigenic component cosmetics comprise HBe antigen, HBs surface antigen, diphtheria toxoid, tetanus toxoid, amyloid beta albumen etc.Blood circulation promotes that composition comprises unsaturated fatty acid, the acid of algae river flowing from Guizhou Province through Hunan into Dongting Lake, nattokinase, citric acid, eritadenine, β mono-glucosan, allicin, carotene, prostaglandin A, two rare propyl disulfide compounds and sulfur aminoacid etc. such as catechol, DHA (docosahexenoic acid).
Microstructured bodies provided by the invention has that experience sense is excellent, long-acting slow-release, be easy to the advantage prepared, painlessly can be inserted into application on human skin, makes that medicine or cosmetic industry composition are slowly degraded in skin histology, controllable sustained-release, has reached best administering effect.
A preparation method for degradable microstructured bodies, comprises the following steps:
The first step, preparation substrate and the gel of micropin, by Biodegradable material water or or buffer preparation become gel to prepare substrate and micropin.Biodegradable material is wherein one or more combinations below can selecting: carboxymethyl starch, starch sulphate, poly-carboxymethyl cellulose, hydroxypropyl emthylcellulose, microcrystalline Cellulose, pregelatinized Starch, carboxymethyl cellulose, ethylhydroxyethylcellulose, cellulose acetate-phthalate, methylcellulose, carboxy-propyl cellulose, hydroxy alkyl cellulose, alkylcellulose, polyvinylpyrrolidone, polylactic acid, polyvinyl alcohol, polyacrylamide polymer, polydimethylsiloxane, chondroitin sulfate, poly lactic-co-glycolic acid, dextrin, polrvinyl chloride, chitosan, xanthan gum, dextran, polyglutamic acid, fibroin, hyaluronic acid, collagen protein, gelatin, oligopeptide.Buffer solution can be common neutral buffer, the isotonic phosphate buffer of neutral physiological, physiological saline wherein one or more.Add in the gel preparing micropin following ease pain material wherein one or more: morphine, bupivacaine, lignocaine, carticaine, cocaine, cincaine, cinchocaine, etidocaine, prilocaine, tetracaine, benzocaine, butacaine, oxybuprocaine, procaine, fexicaine, tricaine, adding concentration range is 0.001%-20% (W/W) or 0.01%-15% (W/W), can also be 0.02%-10% (W/W) or 0.03%-8% (W/W), also can be 0.05%-5% (W/W) or 0.1%-3% (W/W), can be preferably 0.2%-2% (W/W) or 0.3%-1.5% (W/W), it is recommended that 0.5%-1% (W/W), then mix.
In order to extend the degradation cycle of Biodegradable material, the general Biodegradable material adopting macromolecule, also increases molecular weight to realize by modes such as modifications.In order to reduce the degradation rate of the micropin inserting skin, improve the long-acting slow-release effect of microstructured bodies, the gel preparing micropin can adopt the cross-linked derivant of Biodegradable material, one or more compound modes can be selected realize, such as, can directly cross-linked-hyaluronic acid, collagen protein or gelatin, also can adopt the mixing cross-linking products of hyaluronic acid, collagen protein or gelatin, certainly can also adopt the mode that cross-linking products mixture and non-cross-linked materials combine.The gel preferred molecular weight of micropin is the polymer hyaluronic acid cross-linked derivant of 1.0-4.0MDa, also can be the cross-linked derivant that high molecular weight hyaluronic acid and molecular weight are less than the hyaluronic acid mixtures of 1.0MDa, can also be the compositions of high molecular weight hyaluronic acid cross-linking products and low-molecular-weight hyaluronic acid or the compositions of low-molecular-weight hyaluronic acid cross-linking products and high molecular weight hyaluronic acid.
Second step, provides mould (1): mould has hole (5), hole does not penetrate mould.Dark (2) scope in hole is 0.2-2.5mm, and hole spacing (3) scope is 0.1-2.5mm, and hole dia (4) scope is 1-300 μm.Mould can be monometallic material, alloy material, or high molecular polymer material, any one in such as titanium, copper, aluminum, nickel, tungsten, rustless steel, titanium alloy, nickel alloy, aluminium alloy, copper alloy or other metals or alloy, or the material such as polystyrene, politef, can also be any one in the materials such as glass, silicon, silicon dioxide, there is stronger hardness and the characteristic such as rigidity, smooth surface.
3rd step, 20%-90% (V/V) first step is injected in the hole to mould provides the gel preparing micropin being added with analgesia material, then fills the gel of the preparation substrate that the first step provides to the hole of mould.
Often be added with in the gel preparing micropin as medicine or cosmetic composition, reach the object of administration.In gel, usually add medicine or cosmetic industry composition, adding concentration will match with microstructured bodies speed, Human Tolerance limit value and the absorption rate discharging medicine or cosmetic industry composition of degrading, to reach the object of controlled degradation, long-acting slow-release.When adding medicine or cosmetic industry composition, temperature requirement is not higher than 37 DEG C, and adding temperature principle is that temperature can not destroy medicine or cosmetic industry composition.At biological medicine and medical field, can be one or more combinations in vaccine, hormone, genetically engineered drug, polypeptide, polysaccharide, ucleotides, protein-based, chemicals, natural drug, nutritional labeling as the material of active ingredient.At beauty treatment fields, as wherein one or more compositions below can the comprising of cosmetic industry composition: white-skinned face function composition, moisture-keeping efficacy composition, anti-ageing functional component, acne-removing composition, acne removing scar functional component, remove red blood streak functional component, light scar functional component, remove freckle functional component, skin care functional component, treatment chloasma functional component, sun-proof function composition, moisten functional component, lock water functional component, wrinkle removing functional component, anti-inflammatory effect composition, antiallergic functional component, toxin expelling functional component.
4th step, then dry solidification, then demoulding sterilizing.Because solidification temperature and hardening time affect very crucial for product, require that solidification can not destroy drug effect or cosmetic industry composition, physicochemical property and the degradation property of Biodegradable material can not be affected.Therefore, have application claims dry solidification temperature and hardening time a better combination, solidification temperature scope is 25 DEG C-60 DEG C, hardening time 5s-36h not etc., mainly carry out selection time according to the mode of drying.The mode of dry solidification can adopt one or more combinations in heat drying, blowing drying, lyophilization, drying at room temperature and drying under reduced pressure.Microstructured bodies adopts oxirane or irradiation sterilization.
Microstructured bodies prepared by this method has and painlessly pierces through skin, and preparation technology is simple, the advantage with long-acting slow-release, may be used for biological medicine and medical and beauty treatment fields.
Accompanying drawing explanation
Fig. 1 is the overall schematic of the aseptic microstructured bodies of the present invention, and 1 in figure is micropin schematic diagram, and 2 is schematic diagrams of substrate, and 3 is analgesia material schematic diagrams.
Fig. 2 is the overall schematic of mould of the present invention, 1 mould schematic diagram in figure, and 2 is the dark schematic diagrams in hole, and 3 is schematic diagrams of hole spacing, and 4 is schematic diagrams of hole dia, and 5 is the schematic diagrams in hole.
Embodiment
Embodiment one: the performance of microstructured bodies
In this experiment, the substrate main component of microstructured bodies is chitosan and dextrin, and micropin diameter, micropin length and micropin centre-to-centre spacing are 150 μm, 0.5mm and 0.1mm respectively, and microstructured bodies pH is 7.1, and other parameters of microstructured bodies are in table 1.
Table 1.
Embodiment two: the susceptibility of microstructured bodies
In this experiment, the substrate main component of microstructured bodies is ethylhydroxyethylcellulose, polylactic acid and hydroxy methocel, not drug containing or cosmetic composition, micropin diameter, micropin length and micropin centre-to-centre spacing are 120 μm, 0.5mm and 0.1mm respectively, microstructured bodies pH is 7.3, and other performance parameters of microstructured bodies are in table 2.Note: microstructured bodies is from experiencing intensity during insertion skin and time duration after inserting, and susceptibility is divided into: poor, poor, general, better, good, good.
Table 2
Embodiment three: the degradation property of microstructured bodies
In this experiment, compared for several microstructured bodies degradation property, substrate is poly lactic-co-glycolic acid, and micropin diameter, micropin length and micropin centre-to-centre spacing are 100 μm, 0.6mm and 0.15mm respectively, and microstructured bodies pH is 7.5, and other performance parameters are in table 3.
The micropin of the microstructured bodies of 0.5g is loaded 1ml centrifuge tube, in each pipe, adds 200 μ l hyaluronidase and/or collagenase solutions, make the activity of enzyme be 30IU/ml.The sample be consistent with not enzyme-added, other operations is for reference substance.37 DEG C of constant temperature 16 hours.By centrifugal for each pipe after reaction, outwell supernatant, measure the example weight remained in bottom pipe.By the example weight measurement result of the trial target of each sample and reference substance with the calculating of theoretical residual sample percentage rate (%), percentage ratio higher explanation long-acting slow-release effect is more lasting, and concrete data are in table 3.
Embodiment four: prepare microstructured bodies
Get 0.5g collagen, 0.02g dextrin dissolve 10ml water, add 1mgN-N-Hydroxysuccinimide and 1-ethyl-3-(3-dimethylamino-propyl)-carbodiimide, regulate pH5.5,25 DEG C crosslinked 16 hours, form gel, quadrisection.Then 0.001g lignocaine is added in a gel wherein, instillation titanium alloy material mould after mixing: hole is 0.2mm deeply, and hole spacing is 0.5mm, and hole dia scope is 50 μm, general 90% (V/V).Then with the full mould of another part of gel drops, the gel on mould is struck off with instrument, then not higher than dry solidification at 45 DEG C, ethylene oxide sterilizing.The performance parameter of microstructured bodies prepared by this method is in table 4.
Table 4.
Embodiment five: prepare microstructured bodies
A gel in Example four, 0.02g morphine and 200 units of insulin are added wherein, instillation politef material mould after mixing: hole is 0.8mm deeply, and hole spacing is 0.3mm in a gel, hole dia is 150 μm, general 50% (V/V).Then with the full mould of remaining a gel drops, the gel on mould is struck off with instrument, then dry solidification under natural wind, Co
60sterilizing.The performance parameter of microstructured bodies prepared by this method is in table 5.
Table 5.
Embodiment six: prepare microstructured bodies
In 20mlpH8.5 water, add 0.01g1,4-butanediol glycidyl ether, then adding 3g molecular weight is 1.2MDa hyaluronic acid, within crosslinked 6 hours, forms gel, then adds 1g etidocaine, stir, be divided into quarter.A interpolation 0.002g sodium ascorbyl phosphate disodium hydrogen and 0.001gVe wherein, instill mould after mixing: hole is 0.3mm deeply, and hole spacing is 0.1mm, hole dia is 80 μm, general 90% (V/V).Then with the full mould of other a gel drops, the gel on mould is struck off with instrument, then 25 DEG C of dry solidification demouldings after 36 hours, ethylene oxide sterilizing.The performance parameter of microstructured bodies prepared by this method is in table 6.
Table 6.
Embodiment seven: prepare microstructured bodies
Example six remains a copy of it gel, adds Anti-HBs antibody 150IU wherein, instill mould after mixing in a gel: hole is 2.5mm deeply, and hole spacing is 0.5mm, and hole dia is 250 μm, general 20% (V/V).Then with the full mould of the remaining a gel drops of embodiment six, the gel on mould is struck off with instrument, then dry solidification under natural wind, Co
60sterilizing.The performance parameter of microstructured bodies prepared by this method is in table 7.
Table 7.
Embodiment eight: microstructured bodies degradation property
For the microstructured bodies degradation property of embodiment four to embodiment seven, degradation property method of testing is consistent with embodiment three, and the degradation property parameter of microstructured bodies is in table 8.
Table 8.
| Numbering | Percentage ratio (%) |
| 4-1 | 40 |
| 5-1 | 42 |
| 6-1 | 51 |
| 7-1 | 47 |
Percentage ratio is higher, illustrates that microstructured bodies degraded is slower, and that medicine in microstructured bodies or cosmetic composition discharge is slower, and namely microstructured bodies long-acting slow-release is imitated.
Claims (10)
1. a degradable microstructured bodies, the substrate of standing thereon primarily of micropin and micropin is formed, and it is characterized in that, micropin contains analgesia material.
2. degradable microstructured bodies according to claim 1, it is characterized in that, the analgesia material that micropin contains be morphine, bupivacaine, lignocaine, carticaine, cocaine, cincaine, cinchocaine, etidocaine, prilocaine, tetracaine, benzocaine, butacaine, oxybuprocaine, procaine, fexicaine, tricaine wherein one or more.
3. degradable microstructured bodies according to claim 2, it is characterized in that, described micropin comprises the derivant of one or more following materials: carboxymethyl starch, starch sulphate, poly-carboxymethyl cellulose, hydroxypropyl emthylcellulose, microcrystalline Cellulose, pregelatinized Starch, carboxymethyl cellulose, ethylhydroxyethylcellulose, cellulose acetate-phthalate, methylcellulose, carboxy-propyl cellulose, hydroxy alkyl cellulose, alkylcellulose, polyvinylpyrrolidone, polylactic acid, polyvinyl alcohol, polyacrylamide polymer, polydimethylsiloxane, chondroitin sulfate, poly lactic-co-glycolic acid, dextrin, polrvinyl chloride, chitosan, xanthan gum, dextran, polyglutamic acid, hyaluronic acid, collagen protein, gelatin, few tire.
4. degradable microstructured bodies according to claim 3, is characterized in that, described micropin contains medicine or cosmetic composition.
5. degradable microstructured bodies according to claim 4, it is characterized in that, described ingredient comprises one or more combinations in vaccine, hormone, genetically engineered drug, polypeptide, polysaccharide, ucleosides, protein-based, chemicals, natural drug, nutritional labeling.
6. degradable microstructured bodies according to claim 4, it is characterized in that, described cosmetic composition comprises wherein one or more combinations of following functional component: white-skinned face function composition, moisture-keeping efficacy composition, anti-ageing functional component, acne-removing composition, acne removing scar functional component, remove red blood streak functional component, light scar functional component, remove freckle functional component, skin care functional component, treatment chloasma functional component, sun-proof function composition, moisten functional component, lock water functional component, wrinkle removing functional component, anti-inflammatory effect composition, antiallergic functional component, toxin expelling functional component, blood circulation promotes composition.
7. a preparation method for degradable microstructured bodies, comprising: 1), provide gel: Biodegradable material is softened into the gel preparing micropin and substrate, adds analgesia material to the gel preparing micropin; 2) mould (1) is provided: dark (2) scope in hole is 0.2-2.5mm, and hole spacing (3) scope is 0.1-2.5mm, and hole dia (4) scope is 1-300 μm; 3), injection molding: 20%-90%(V/V is injected in the hole to mould) be added with 1 of analgesia material) prepare the gel of micropin, then fill 1 to the hole of mould) in the gel of preparation substrate; 4), sterilizing is solidified: curing and demolding, oxirane or irradiation sterilization.
8. the preparation method of degradable microstructured bodies according to claim 7, it is characterized in that, described 1) gel preparing micropin in also comprises with N-hydroxy-succinamide, 1,2,7,8-diepoxyoctane, BDO glycidyl ether, ethylene glycol and glycidyl ether, 1-ethyl-3-(3-dimethylamino-propyl)-carbodiimide, divinylsulfone, Polyethylene Glycol, 1,3-butane diepoxide, genipin wherein one or more cross-linking agents steps.
9. the preparation method of degradable microstructured bodies according to claim 8, is characterized in that, described 1) step also the oriented gel preparing micropin add the step of medicine or cosmetic composition.
10. the preparation method of degradable microstructured bodies according to any one of claim 7-9, it is characterized in that, described analgesia material be morphine, bupivacaine, lignocaine, carticaine, cocaine, cincaine, cinchocaine, etidocaine, prilocaine, tetracaine, benzocaine, butacaine, oxybuprocaine, procaine, fexicaine, tricaine wherein one or more.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201511024530.0A CN105411997A (en) | 2015-12-30 | 2015-12-30 | Degradable microstructure body and preparation method thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201511024530.0A CN105411997A (en) | 2015-12-30 | 2015-12-30 | Degradable microstructure body and preparation method thereof |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN105411997A true CN105411997A (en) | 2016-03-23 |
Family
ID=55490856
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201511024530.0A Pending CN105411997A (en) | 2015-12-30 | 2015-12-30 | Degradable microstructure body and preparation method thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN105411997A (en) |
Cited By (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105879213A (en) * | 2016-04-19 | 2016-08-24 | 浙江理工大学 | Biodegradable calcium sulfate/gelatin composite micro needle array patch and preparation method thereof |
| CN106074360A (en) * | 2016-06-29 | 2016-11-09 | 莆田学院 | A kind of solubility microneedle preparation method towards poorly water soluble drugs |
| CN107343984A (en) * | 2017-05-16 | 2017-11-14 | 怡定兴科技股份有限公司 | Method for manufacturing medical micro-needle patch |
| CN107375111A (en) * | 2017-08-30 | 2017-11-24 | 陈彦彪 | A kind of soluble anti-acne micropin |
| CN107569421A (en) * | 2017-09-18 | 2018-01-12 | 陈彦彪 | A kind of soluble nti-freckle micropin |
| CN109200012A (en) * | 2017-07-06 | 2019-01-15 | 中科微针（北京）科技有限公司 | A kind of layering dissolution micropin containing inorganic salts |
| CN109907979A (en) * | 2019-04-30 | 2019-06-21 | 江苏熙美生物科技有限公司 | Intradermal needling and preparation method thereof |
| CN110115707A (en) * | 2018-02-07 | 2019-08-13 | 华中科技大学 | A kind of method and its application preparing porous polymer micropin based on phase detachment technique |
| CN110740759A (en) * | 2017-04-05 | 2020-01-31 | 吉莱斯公司 | Improved superabsorbent material and method of making same |
| CN111494237A (en) * | 2020-04-30 | 2020-08-07 | 重庆福特尔科技有限公司 | Soluble micro-needle patch |
| CN112237574A (en) * | 2019-07-18 | 2021-01-19 | 复旦大学 | Recombinant hirudin micro-needle drug delivery system and preparation method thereof |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101687090A (en) * | 2007-05-15 | 2010-03-31 | 考司美德制药株式会社 | Microneedle device and method for producing the same |
| CN101868229A (en) * | 2007-11-21 | 2010-10-20 | 株式会社培旺精廉宅 | Preparation for application to body surface and preparation holding sheet for application to body surface |
| CN103889497A (en) * | 2011-10-20 | 2014-06-25 | 考司美德制药株式会社 | Microneedle deposition technique |
-
2015
- 2015-12-30 CN CN201511024530.0A patent/CN105411997A/en active Pending
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101687090A (en) * | 2007-05-15 | 2010-03-31 | 考司美德制药株式会社 | Microneedle device and method for producing the same |
| CN101868229A (en) * | 2007-11-21 | 2010-10-20 | 株式会社培旺精廉宅 | Preparation for application to body surface and preparation holding sheet for application to body surface |
| CN103889497A (en) * | 2011-10-20 | 2014-06-25 | 考司美德制药株式会社 | Microneedle deposition technique |
Cited By (15)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105879213B (en) * | 2016-04-19 | 2019-04-16 | 浙江理工大学 | Biodegradable calcium sulfate/gelatin-compounded microneedle array patch and preparation method thereof |
| CN105879213A (en) * | 2016-04-19 | 2016-08-24 | 浙江理工大学 | Biodegradable calcium sulfate/gelatin composite micro needle array patch and preparation method thereof |
| CN106074360A (en) * | 2016-06-29 | 2016-11-09 | 莆田学院 | A kind of solubility microneedle preparation method towards poorly water soluble drugs |
| CN110740759A (en) * | 2017-04-05 | 2020-01-31 | 吉莱斯公司 | Improved superabsorbent material and method of making same |
| CN110740759B (en) * | 2017-04-05 | 2022-05-06 | 吉莱斯公司 | Improved superabsorbent materials and methods for making the same |
| CN107343984A (en) * | 2017-05-16 | 2017-11-14 | 怡定兴科技股份有限公司 | Method for manufacturing medical micro-needle patch |
| CN107343984B (en) * | 2017-05-16 | 2021-02-02 | 怡定兴科技股份有限公司 | Method for manufacturing medical micro-needle patch |
| CN109200012A (en) * | 2017-07-06 | 2019-01-15 | 中科微针（北京）科技有限公司 | A kind of layering dissolution micropin containing inorganic salts |
| CN107375111A (en) * | 2017-08-30 | 2017-11-24 | 陈彦彪 | A kind of soluble anti-acne micropin |
| CN107569421A (en) * | 2017-09-18 | 2018-01-12 | 陈彦彪 | A kind of soluble nti-freckle micropin |
| CN110115707A (en) * | 2018-02-07 | 2019-08-13 | 华中科技大学 | A kind of method and its application preparing porous polymer micropin based on phase detachment technique |
| CN110115707B (en) * | 2018-02-07 | 2021-01-19 | 华中科技大学 | Method for preparing porous polymer microneedle based on phase separation technology and application thereof |
| CN109907979A (en) * | 2019-04-30 | 2019-06-21 | 江苏熙美生物科技有限公司 | Intradermal needling and preparation method thereof |
| CN112237574A (en) * | 2019-07-18 | 2021-01-19 | 复旦大学 | Recombinant hirudin micro-needle drug delivery system and preparation method thereof |
| CN111494237A (en) * | 2020-04-30 | 2020-08-07 | 重庆福特尔科技有限公司 | Soluble micro-needle patch |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN105411997A (en) | Degradable microstructure body and preparation method thereof | |
| Dabholkar et al. | Biodegradable microneedles fabricated with carbohydrates and proteins: Revolutionary approach for transdermal drug delivery | |
| CN103501852B (en) | The manufacture method of microstructured bodies | |
| Prausnitz | Engineering microneedle patches for vaccination and drug delivery to skin | |
| KR101747099B1 (en) | Method of Preparing Micro-Needle Using Biocompatible Polymer | |
| JP5472770B2 (en) | Short melting microneedle | |
| KR101830398B1 (en) | Painless and Patchless Shooting Microstructures | |
| CN105073178B (en) | Microarray and its application method for therapeutic agent delivering | |
| CN111904951A (en) | Microneedle patch and preparation method thereof | |
| US20110177297A1 (en) | Method of manufacturing solid microstructure and solid microstructure manufactured based on same | |
| CN105797266A (en) | Micro-structure body and preparation method thereof | |
| Kang et al. | Microneedles for drug delivery: recent advances in materials and geometry for preclinical and clinical studies | |
| CN105078880A (en) | Macromolecular soluble microneedle used for cutaneous penetration of polypeptide and protein medicines and preparation method of macromolecular soluble microneedle | |
| US20200016388A1 (en) | Microneedle array with composite formulation, and method for manufacturing same | |
| JP2009273872A (en) | Microneedle array | |
| EP3563900B1 (en) | Microneedle array coated with drug | |
| CN109045460A (en) | A kind of microneedle patch and preparation method thereof | |
| Amourizi et al. | Polymeric and composite-based microneedles in drug delivery: regenerative medicine, microbial infection therapy, and cancer treatment | |
| CN205360022U (en) | A polymer soluble micropin that is used for polypeptide and protein drug transdermal to dose | |
| CN100408126C (en) | Preparing method for epidermis needle and its application | |
| Chen et al. | Strategies to develop polymeric microneedles for controlled drug release | |
| CN105498081A (en) | Sterile microstructure body and preparation method thereof | |
| WO2010093528A2 (en) | On-demand and reversible drug release by external cue | |
| KR102227989B1 (en) | Microstructure-based drug injection device and manufacturing method thereof | |
| CN106422046A (en) | Jet micro-needle injection system |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into 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: 20160323 |