CN106667897A - Biodegradable slow/controlled-release drug delivery system and preparation method thereof - Google Patents

Biodegradable slow/controlled-release drug delivery system and preparation method thereof Download PDF

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Publication number
CN106667897A
CN106667897A CN201710084574.5A CN201710084574A CN106667897A CN 106667897 A CN106667897 A CN 106667897A CN 201710084574 A CN201710084574 A CN 201710084574A CN 106667897 A CN106667897 A CN 106667897A
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methyl
acid
drug
biodegradable
diketone
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杨立群
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LIAONING RESEARCH INSTITUTE OF FAMILY PLANNING
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LIAONING RESEARCH INSTITUTE OF FAMILY PLANNING
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/007—Pulmonary tract; Aromatherapy
    • 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
    • A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
    • A61K31/19—Carboxylic acids, e.g. valproic acid
    • A61K31/192—Carboxylic acids, e.g. valproic acid having aromatic groups, e.g. sulindac, 2-aryl-propionic acids, ethacrynic acid 
    • 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
    • A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
    • A61K31/565—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids not substituted in position 17 beta by a carbon atom, e.g. estrane, estradiol
    • A61K31/567—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids not substituted in position 17 beta by a carbon atom, e.g. estrane, estradiol substituted in position 17 alpha, e.g. mestranol, norethandrolone
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
    • 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
    • A61K47/34—Macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyesters, polyamino acids, polysiloxanes, polyphosphazines, copolymers of polyalkylene glycol or poloxamers
    • 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
    • A61K9/0002—Galenical forms characterised by the drug release technique; Application systems commanded by energy
    • 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
    • A61K9/0014—Skin, i.e. galenical aspects of topical compositions
    • 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
    • A61K9/0024—Solid, semi-solid or solidifying implants, which are implanted or injected in body tissue
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L17/00—Materials for surgical sutures or for ligaturing blood vessels ; Materials for prostheses or catheters
    • A61L17/005—Materials for surgical sutures or for ligaturing blood vessels ; Materials for prostheses or catheters containing a biologically active substance, e.g. a medicament or a biocide
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L17/00—Materials for surgical sutures or for ligaturing blood vessels ; Materials for prostheses or catheters
    • A61L17/06—At least partially resorbable materials
    • A61L17/10—At least partially resorbable materials containing macromolecular materials
    • A61L17/105—Polyesters not covered by A61L17/12
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/14—Macromolecular materials
    • A61L27/18—Macromolecular materials obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/50—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
    • A61L27/54—Biologically active materials, e.g. therapeutic substances
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/50—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
    • A61L27/58—Materials at least partially resorbable by the body
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L31/00—Materials for other surgical articles, e.g. stents, stent-grafts, shunts, surgical drapes, guide wires, materials for adhesion prevention, occluding devices, surgical gloves, tissue fixation devices
    • A61L31/04—Macromolecular materials
    • A61L31/06—Macromolecular materials obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L31/00—Materials for other surgical articles, e.g. stents, stent-grafts, shunts, surgical drapes, guide wires, materials for adhesion prevention, occluding devices, surgical gloves, tissue fixation devices
    • A61L31/14—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
    • A61L31/148—Materials at least partially resorbable by the body
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L31/00—Materials for other surgical articles, e.g. stents, stent-grafts, shunts, surgical drapes, guide wires, materials for adhesion prevention, occluding devices, surgical gloves, tissue fixation devices
    • A61L31/14—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
    • A61L31/16—Biologically active materials, e.g. therapeutic substances
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
    • A61L2300/20—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices containing or releasing organic materials
    • A61L2300/216—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices containing or releasing organic materials with other specific functional groups, e.g. aldehydes, ketones, phenols, quaternary phosphonium groups
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    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
    • A61L2300/20—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices containing or releasing organic materials
    • A61L2300/22—Lipids, fatty acids, e.g. prostaglandins, oils, fats, waxes
    • A61L2300/222—Steroids, e.g. corticosteroids

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  • Proteomics, Peptides & Aminoacids (AREA)
  • Inorganic Chemistry (AREA)
  • Pulmonology (AREA)
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Abstract

The invention relates to the fields of chemical and medical biological materials and biomedicine, and particularly relates to a biodegradable slow/controlled-release drug delivery system and a preparation method thereof. The system using one or more than two biodegradable three-dimensional network polymers or biodegradable crosslinked elastomers as a drug carrier, and the drug content in the system by weight is more than 0-50%.By using the biodegradable three-dimensional network polymers as the drug carrier, the drug is loaded on the drug carrier through a swelling method. The process provided by the invention is simple and easy to operate; and the drug loading capacity of the drug delivery system can be changed by changing the concentration of a drug solution, the physical behavior of a drug carrier product, dimension parameters and the other parameters. The system has higher application prospects in the fields of tissue engineering and drug slow release, and can be used for disease prevention and treatment and other aspects through surgical sutures, anti-adhesive membranes, tissue engineering scaffolds, subcutaneous implants, contraceptive implants and transdermal or inhalation drug delivery.

Description

A kind of Biodegradable slowly released and controlled-drug delivery system and preparation method thereof
Technical field
The present invention relates to chemistry, biomaterial for medical purpose and biologic pharmacological science field, specifically a kind of biodegradation Type slowly released and controlled-drug delivery system and preparation method thereof.
Background technology
Drug controlled release is conducive to improving curative effect of medication, reduces toxic and side effects, can mitigate the pain of the multiple medication of patient, Be significant for clinical application level is improved, be research in international coverage in recent years most popular field it One.For a long time, it is always in drug controlled release field based on the pharmaceutical carrier of macromolecular material and studies for enlivening the most Individual system.The eighties in 20th century, Segal etc. are occurred in earliest with silicone rubber work using macromolecule as the delivery systme of pharmaceutical carrier For carrier material, Progesterone is mounted in silicone rubber microcapsule for family planning research.Result of study shows that medicine is when longer Interior slow release, therapeutic effect is satisfactory.But problem is it is found that organosilicon material can induce after long-term use Canceration, thus the safety to this kind of material proposes objection.Meanwhile, because of its non-degradable characteristic, silicone rubber can not drop in vivo Solve as micromolecular compound and be absorbed by organisms or metabolism, place and need second operation to take out after exhaustion of effect.But due to taking Go out operation more than implant surgery difficulty, not only increased use cost, bring unnecessary pain, Er Qienan to user Can take out on schedule in all user of guarantee.
In order to overcome disadvantages mentioned above, scientific research personnel is devoted to studying always biodegradable polymer, and expect with This eliminates the inconvenience that second operation is brought as drug carrier material.Since the eighties in 20th century, although have tens kinds to gather Compound is proposed as degradable biological material, but so far only a few is approved by the FDA in the United States human implantable, Such as：PTMC, polycaprolactone, PGA, polylactide and its copolymer etc., in the medicine sustained and controlled release side of putting Face obtains Preliminary Applications.Although these biodegradable linear polyesters can be with degradation in vivo as micromolecular compound and by body Absorb, it is to avoid the trouble that second operation takes out, but the problem that generally existing structure is not sufficiently stable so that medicine-carried system carrying drug ratio Low, poor controllability, before medicine is not discharged completely, it is impossible to keep good mechanical property and collapse, cause medicine Thing " burst release ", is precisely controlled release and also has very big gap apart from medicine, and to user great side effect even life is brought Danger, hinders or limits their applications in medicine sustained and controlled release field.Therefore, the continuous renewal with clinical demand and base In these biodegradable linear polyesters functional material biomedicine field continuous application and expansion, exploitation one class knot Structure is more stable, the adjustable new slow controlled-release material of degradation time is imperative.Biodegradation three-dimensional network polymer or life Thing degradation-type cross-linked elastomer has stable three-dimensional net structure, excellent pliability, elasticity and other line styles such as modulus can The mechanical performance that degraded medical macromolecular materials are lacked, it is ensured that pharmaceutical carrier generates space in degradation process, forms The spongy space structure of class, and after occurring largely to degrade, remains to keep original three dimensional structure and good Mechanical performance, the slow controlled release for medicine provides strong guarantee.
Chinese invention patent application (publication number：The A of CN 102989044), there is provided a kind of biodegradable medical high polymer Tubing and preparation method thereof, when polymerization forming method prepares biodegradable cross-linked polymer pipe in using mould, can exist simultaneously Medicine is introduced directly in polymer process, the biodegradable polymers tubing of pastille is obtained.It is disadvantageous in that, directly Introducing medicine can only be free from the medicine of oh group or without the medicine that can participate in polyreaction group, once medicine Group take part in polyreaction, drug inactivation will be caused, and then cause therapeutic effect to reduce, or even life is brought to user It is dangerous.
Chinese invention patent application (publication number：The A of CN 102743329, CN 102743328 A) a kind of new palace is provided A kind of interior slowly released and controlled-drug delivery system and preparation method thereof and biodegradation material in utero slowly released and controlled-drug delivery system and preparation method thereof, It is that medicine is mixed homogeneously with linear polymer or star-type polymer when the two prepares biodegradation cross linked polymer medicated core, Made compound using screw extruder method or die pressing is carried out crosslinking and is prepared after medicated core using irradiation method.Its deficiency Place is that cross-linking radiation can equally destroy the chemical constitution of drug molecule, and then cause drug inactivation, and then cause therapeutic effect Reduce, or even life danger is brought to user.
The content of the invention
For above-mentioned technical problem present in prior art, it is an object of the invention to provide a kind of Biodegradable is slow Controlled-release administrating system and preparation method thereof, can effectively eliminate because pharmaceutical group participates in polyreaction or cross-linking radiation destruction medicine Thing molecular structure and cause the negative effect and potential hazard that drug inactivation brought.
In order to solve above-mentioned technical problem, the technical scheme is that：
A kind of Biodegradable slowly released and controlled-drug delivery system, the system is with one or more Biodegradable three-dimensional networks Polymer or Biodegradable cross-linked elastomer are pharmaceutical carrier, and the drug weight content in system is more than 0 to 50%.
Described Biodegradable slowly released and controlled-drug delivery system, the drug weight preferred content in system is 10~20%.
Described Biodegradable slowly released and controlled-drug delivery system, medicine is hormone medicine, anti-inflammatory analgetic class medicine, antiallergic Class medicine, antifertility class medicine, antitumor class medicine, anti-senile dementia class medicine, anti-schizophrenia class medicine, classes of anti-infective medicine Thing, immunomodulating class medicine, antiproliferative pharmaceutical, neuroleptic and neurasthenia treating class medicine or polypeptide protein and vaccine Bio-pharmaceutical.
Described Biodegradable slowly released and controlled-drug delivery system, pharmaceutical carrier article shape variation, using wire, it is bar-shaped, Tubulose, lamellar, membranaceous, graininess, powder, weaving object, solid or irregularly shaped body.
Described Biodegradable slowly released and controlled-drug delivery system, Biodegradable three-dimensional network polymer is Acetic acid, hydroxy-, bimol. cyclic ester, L- third Lactide, DL- lactides, beta-propiolactone, (R, S)-Alpha-Methyl -- propiolactone, 3- methyl-ss-propiolactones, β-benzyloxycarbonyl group-β-the third Lactone, beta-butyrolactone, gamma-butyrolacton, α-bromo- gamma-butyrolacton, alpha-methylene-gamma-butyrolactone, (R) -3- hydroxyl-γ-Ding Nei Ester, (R)-(-) -4- methylol butyrolactone, (S)-(+) -4- methylol butyrolactone, (S)-(-)-Alpha-hydroxy-gamma-butyrolacton, (S) -3- hydroxy-gamma-butyrolactones, DL- Alpha-hydroxies-beta, beta-dimethyl-gamma-butyrolacton, δ-valerolactone, Beta-methyl-δ-valerolactone, (R) -4- methyl-δ-valerolactone, DL- Beta-methyls-beta-hydroxy-δ-valerolactone, (R) -5- methyl-δ-valerolactone, gamma-valerolactone, 6-caprolactone, δ-caprolactone, γ-hexalactone, 5- hydroxyl caprolactones, 3- methyl -4- oxo -6- caprolactones, 3- methyl-ε-oneself in Ester, 4- methyl-epsilon-caprolactones, 4- ethyl-s-caprolactones, 4- propyl group -6-caprolactone, 5- methyl-epsilon-caprolactones, 6- methyl-ε - Caprolactone, γ-heptalactone, 7- methyl heptalactones；γ-octalactone, δ-octalactone, 8- methyl caprylolactones, 4- hydroxy-3-methyls- Caprylolactone, 1,4- caprylolactones, nonyl lactone, δ-nonalactone, γ-decalactone, δ-decalactone, ε-decalactone, 4- hydroxyls 11 Acid-gamma lactone, δ-dodecalactone, γ-dodecalactone, 12- methyl-dodecalactone, in 2- methylene -4- oxos -12- 12 Ester, trimethylene carbonate, 5- benzyloxy trimethylene carbonates, 5- benzyloxycarbonyl group trimethylene carbonates, 5- allyloxys Trimethylene carbonate, 5- methyl -5- benzyloxycarbonyl group trimethylene carbonates, 5- ethyl -5- methylol trimethylene carbonates, 5- ethyl -5- phenyl trimethylene carbonates, 5- ethyl -5- butyl trimethylene carbonates, 2,2- dimethyltrimethylene carbon The propargyl oxygen carbonyl trimethylene carbonate of acid esters, 2- ethoxycarbonyl-2-methyl trimethylene carbonates, 2- methyl -2-, 2- first Base -2- allyloxycarbonyl trimethylene carbonates, 2- methyl -2- Cortex Cinnamomi acyl-oxygen methyl trimethylene carbonates, 2- ethyl -2- meat Osmanthus acyloxymethyl trimethylene carbonate, 2,4- dioxo spiros [5.5] hendecane -3- ketone, 1- vinyl -2,4- dioxo spiros [5.5] hendecane -3- ketone, 1,3- dioxolan-2-ones, 1,4- dioxane-2-ketones, 5- benzyloxymethyl -1,4- dioxane - 2- ketone, 1,5- Dioxepane -2- ketone, caprolactam, N- acetyl caprolactams, N- caprolactams, DL- amino oneself Lactams, 3- inferior pentenyl -4- butyrolactams, N- bromine caprolactams, N- methyl caprolactam, oenantholcatam, (±)-α-ammonia Base-epsilon-caprolactams, morpholine -2,5- diketone, 3- methyl morpholine -2,5- diketone, 3- (benzyloxycarbonyl group ethyl)-morpholine -2,5- bis- Ketone, (3S) -3- (benzyloxycarbonyl-methyl) morpholine -2,5- diketone, (3S, 6RS) -3- (benzyloxycarbonyl-methyl) -6- Methyl-morpholines - 2,5- diketone, (3s, 6RS) -3- [4- (benzyloxycarbonyl amino) butyl] -6- Methyl-morpholine -2,5- diketone, (3S, 6RS) -3- couple Thio methylol -6- Methyl-morpholines -2,5- the diketone of methoxybenzyl, 3-N- benzyloxycarbonyl groups lysyl--morpholine -2,5- diketone, 6- Isopropyl-morpholine -2,5- diketone, 6- isopropyl -3- Methyl-morpholine -2,5- diketone, maleic anhydride, succinic anhydride, methyl fourth two Anhydride, 2- methylene-succinic anhydride, tetrafluoro succinic anhydride, glutaric anhydride, 3,3- tetramethyleneglutaric acid acid anhydrides, 3,3- dimethyl Glutaric anhydride, 2,2- dimethylated pentanedioic acid acid anhydrides, 3- ethyl -3- methylglutaric acid acid anhydrides, hexafluoroglutaric anhydride, adipic anhydride, the last of the ten Heavenly stems two Anhydride, N- carboxyl-L-Alanine-ring inner-acid anhydrides, 2- methoxyl group -2- oxygen -1,3,2- dioxaphospholane, 2- ethyoxyl -2- Oxygen -1,3,2- dioxaphospholane, 2- chloroethoxy -2- oxygen -1,3,2- dioxaphospholane, the chloro- 2- oxygen -1,3,2- of 2- Propargyl epoxide -2- oxygen -1,3,2- the dioxaphospholane of dioxaphospholane, 2-, 5,5- dimethyl -2- oxygen -1,3,2- two The chloro- 1,3,2- dioxaphosphorinanes -2- ketone of oxygen phospholane, 5,5- dimethyl -2-, ethylidene ethyl phosphonic acid ester EEP, Asia Ethyl isobutyl base phosphate ester EIBP, ethylidene 1-isobutyl-3,5-dimethylhexylphosphoric acid ELP, ethylidene octadecyl phosphate ester ESP and its derivative One or more in the cross-linked homopolymer or cross-linked copolymer of thing；
Biodegradable cross-linked elastomer is network polyester, the poly- decanedioic acid glycerol of polynary aromatic acid and polycaprolactone glycol Ester, poly- citric acid ethohexadiol ester, poly- decanedioic acid-ethylene glycol-glyceride, hydroxy alkanoic acid be modified the acid of poly- hydroxy alkyl, Polyethylene Glycol/ Poly terephthalic acid based block copolymer, polybutylene terephthalate (PBT)-co- polycyclohexylene's diformazan alcohol esters- B- Polyethylene Glycol, polyether ester amides, poly- peptide, poe, thermoplastic starch-based bioelastomer, thermosetting polyester elastomer, One or more in thermosetting polyurethane elastomer, thermo-set polyether ester elastomer.
The preparation method of described Biodegradable slowly released and controlled-drug delivery system, is prepared using swelling method, is comprised the steps：
(1) medicine is dissolved in into organic solvent, the controllable drug solution of compound concentration；
(2) pharmaceutical carrier product is placed in drug solution, is sufficiently stirred for, using the swelling character of pharmaceutical carrier by medicine Solution is absorbed to support material internal；
(3) organic solvent is removed, obtains Biodegradable slowly released and controlled-drug delivery system.
The preparation method of described Biodegradable slowly released and controlled-drug delivery system, gives as needed to the slow controlled release of Biodegradable Medicine system carries out face coat, and coating composition is Acetic acid, hydroxy-, bimol. cyclic ester, L- lactides, DL- lactides, beta-propiolactone, (R, S)-α-first Base -- propiolactone, 3- methyl-ss-propiolactones, β-benzyloxycarbonyl group-beta-propiolactone, beta-butyrolactone, gamma-butyrolacton, α-bromo- γ-fourth Lactone, alpha-methylene-gamma-butyrolactone, (R) -3- hydroxy-gamma-butyrolactones, (R)-(-) -4- methylol butyrolactone, (S)-(+) - 4- methylol butyrolactone, (S)-(-)-Alpha-hydroxy-gamma-butyrolacton, (S) -3- hydroxy-gamma-butyrolactones, DL- Alpha-hydroxy-β, β-two Methyl-gamma-butyrolactone, δ-valerolactone, Beta-methyl-δ-valerolactone, (R) -4- methyl-δ-valerolactone, DL- Beta-methyl-beta-hydroxies - δ-valerolactone, (R) -5- methyl-δ-valerolactone, gamma-valerolactone, 6-caprolactone, δ-caprolactone, γ-hexalactone, 5- hydroxyls are in oneself Ester, 3- methyl -4- oxo -6- caprolactones, 3- methyl-epsilon-caprolactones, 4- methyl-epsilon-caprolactones, 4- ethyl-s-caprolactones, 4- Propyl group -6-caprolactone, 5- methyl-epsilon-caprolactones, 6- methyl-epsilon-caprolactones, γ-heptalactone, 7- methyl heptalactones；γ-Xin Nei Ester, δ-octalactone, 8- methyl caprylolactones, 4- hydroxy-3-methyls-caprylolactone, 1,4- caprylolactones, nonyl lactone, δ-nonalactone, γ-decalactone, δ-decalactone, ε-decalactone, 4- hydroxyls undecanoic acid-gamma lactone, δ-dodecalactone, γ-dodecalactone, 12- first Base-dodecalactone, 2- methylene -4- oxo -12- dodecalactones, trimethylene carbonate, 5- benzyloxy trimethylene carbonic acid Ester, 5- benzyloxycarbonyl group trimethylene carbonates, 5- allyloxy trimethylene carbonates, the methylene of 5- methyl -5- benzyloxycarbonyl groups three Base carbonic ester, 5- ethyl -5- methylol trimethylene carbonates, 5- ethyl -5- phenyl trimethylene carbonates, 5- ethyl -5- Butyl trimethylene carbonate, 2,2- dimethyltrimethylene carbonates, 2- ethoxycarbonyl-2-methyl trimethylene carbonates, The propargyl oxygen carbonyl trimethylene carbonates of 2- methyl -2-, 2- methyl -2- allyloxycarbonyl trimethylene carbonates, 2- methyl -2- Cortex Cinnamomi acyl-oxygen methyl trimethylene carbonate, 2- ethyl -2- Cortex Cinnamomi acyl-oxygen methyl trimethylene carbonates, 2,4- dioxo spiros [5.5] hendecane -3- ketone, 1- vinyl -2,4- dioxo spiros [5.5] hendecane -3- ketone, 1,3- dioxolan-2-ones, 1,4- Dioxane-2-ketone, 5- benzyloxymethyl -1,4- dioxane-2-ketones, 1,5- Dioxepane -2- ketone, caprolactam, N- Acetyl caprolactam, N- caprolactams, DL- aminocaproic lactams, 3- inferior pentenyl -4- butyrolactams, N- bromines are in oneself Amide, N- methyl caprolactam, oenantholcatam, (±)-alpha-amido-epsilon-caprolactams, morpholine -2,5- diketone, 3- methyl morpholines- 2,5- diketone, 3- (benzyloxycarbonyl group ethyl)-morpholine -2,5- diketone, (3S) -3- (benzyloxycarbonyl-methyl) morpholine -2,5- diketone, (3S, 6RS) -3- (benzyloxycarbonyl-methyl) -6- Methyl-morpholine -2,5- diketone, (3s, 6RS) -3- [4- (benzyloxycarbonyl amino) fourths Base] -6- Methyl-morpholine -2,5- diketone, (3S, 6RS) -3- methylol -6- Methyl-morpholine -2,5-s two thio to methoxybenzyl Ketone, 3-N- benzyloxycarbonyl groups lysyl--morpholine -2,5- diketone, 6- isopropyls-morpholine -2,5- diketone, 6- isopropyl -3- methyl - Morpholine -2,5- diketone, maleic anhydride, succinic anhydride, dimethyl succinic acid acid anhydride, 2- methylene-succinic anhydride, tetrafluoro succinic anhydride, Glutaric anhydride, 3,3- tetramethyleneglutaric acid acid anhydrides, 3,3- dimethylated pentanedioic acid acid anhydrides, 2,2- dimethylated pentanedioic acid acid anhydrides, 3- ethyl -3- Methylglutaric acid acid anhydride, hexafluoroglutaric anhydride, adipic anhydride, sebacic anhydride, N- carboxyl-L-Alanine-ring inner-acid anhydrides, 2- methoxies Base -2- oxygen -1,3,2- dioxaphospholane, 2- ethyoxyl -2- oxygen -1,3,2- dioxaphospholane, 2- chloroethoxy -2- The chloro- 2- oxygen -1,3,2- dioxaphospholane of oxygen -1,3,2- dioxaphospholane, 2-, the propargyl epoxide -2- oxygen -1,3,2- of 2- Dioxaphospholane, 5,5- dimethyl -2- oxygen -1,3,2- dioxaphospholane, the chloro- 1,3,2- bis- of 5,5- dimethyl -2- Oxygen phospha cyclohexane -2- ketone, ethylidene ethyl phosphonic acid ester EEP, ethylidene isobutyl group phosphate ester EIBP, ethylidene dodecyl phosphorus Acid esters ELP, the homopolymer of ethylidene octadecyl phosphate ester ESP and its derivant or copolymer one or more, apply Thickness degree is below 2mm；Or, by Biodegradable slowly released and controlled-drug delivery system loaded in capsule.
The preparation method of described Biodegradable slowly released and controlled-drug delivery system, in step (1), drug solution concentration is controllable, Drug level is preferably 1~10mg/ml.
The preparation method of described Biodegradable slowly released and controlled-drug delivery system, the shape and size of pharmaceutical carrier are arbitrarily adjusted Section, drug loading is controllable therewith.
The application of described Biodegradable slowly released and controlled-drug delivery system, the system is used for operation suture thread, Antiadhesive film, group Weaver's engineering support, subcutaneous implant, contraception implants, transdermal or inhalation.
Advantages of the present invention and beneficial effect are：
1st, Biodegradable slowly released and controlled-drug delivery system of the invention, it is possible to provide the good pharmaceutical carrier of dimensional stability, After occurring largely to degrade, the original three dimensional structure of holding and good mechanical performance are remained to, be that the slow controlled release of medicine is carried For strong guarantee, medicine " burst release " effect produced by the degraded of linear carrier can be effectively eliminated.
2nd, Biodegradable slowly released and controlled-drug delivery system of the invention, article shape variation, is suitably applied different demands Clinical practice.
3rd, Biodegradable slowly released and controlled-drug delivery system of the invention, can be loaded various kinds of drug by the way of swelling load medicine In pharmaceutical carrier, expansion can use medicament categories；Meanwhile, swelling load medicine can be eliminated effectively because pharmaceutical group participates in polyreaction Or cross-linking radiation destruction drug molecular structure, and cause the negative effect and potential hazard that drug inactivation brought.
4th, the drug loading of Biodegradable slowly released and controlled-drug delivery system of the invention can be according to clinical needs, by pharmaceutical carrier Shape, size and Pharmaceutical concentration can adjust arbitrarily.
5th, Biodegradable slowly released and controlled-drug delivery system of the invention, carries prescription formula simple to operate flexibly.
Description of the drawings
Fig. 1 (a)-Fig. 1 (b) is to prepare by pharmaceutical carrier of PTMC three-dimensional network polymer in the present invention Biodegradable slowly released and controlled-drug delivery system scanning electron microscopic picture.Wherein, Fig. 1 (a) is the surface topography of sample after cleaning；Figure 1 (b) is cross-sectional morphology.
Fig. 2 is the slow controlled release of Biodegradable prepared as pharmaceutical carrier with PTMC three-dimensional network polymer Gestodene's release profiles of drug-supplying system.
Specific embodiment
The following example is now given so that those skilled in the art are easier to understand and implement the present invention, but they should not be by It is considered as restriction the scope of the present invention, and is only its example and representative.Relevant research worker is according to foregoing invention content to the present invention The modifications and adaptations of some point of essence are made, protection scope of the present invention is still fallen within.
Embodiment 1
In the present embodiment, Biodegradable slowly released and controlled-drug delivery system and preparation method thereof is as follows：
Precise 100mg gestodene is dissolved in 50ml chloroforms, and configuration concentration is the drug solution of 2mg/ml；Will be long Degree 20mm, the PTMC three-dimensional network polymer bar (its weight is 150mg) of diameter 3mm are placed in drug solution In, take out after 7 days, after placing 1 day naturally, constant weight is dried under vacuum to, obtain the biodegradation that drug loading is 20mg gestodene Type slowly released and controlled-drug delivery system.
As shown in Fig. 1 (a)-Fig. 1 (b), PTMC three-dimensional network polymer of the present invention is pharmaceutical carrier system Standby Biodegradable slowly released and controlled-drug delivery system, with following features：After cleaning, system surfaces are without drug-rich and separate out existing As, the fracture morphology for transshipping medicine implant can be seen that inside it than more loose, medicine crystal can it is dispersed wherein, reach To good load drug effect fruit.
Embodiment 2
In the present embodiment, Biodegradable slowly released and controlled-drug delivery system and preparation method thereof is as follows：
Precise 100mg gestodene is dissolved in 50ml chloroforms, and configuration concentration is the drug solution of 2mg/ml；Will be long Degree 30mm, the PTMC three-dimensional network polymer bar (its weight is 225mg) of diameter 3mm are placed in drug solution In, take out after 7 days, after placing 1 day naturally, constant weight is dried under vacuum to, obtain the biodegradation that drug loading is 30mg gestodene Type slowly released and controlled-drug delivery system.
Embodiment 3
In the present embodiment, Biodegradable slowly released and controlled-drug delivery system and preparation method thereof is as follows：
Precise 100mg gestodene is dissolved in 50ml chloroforms, and configuration concentration is the drug solution of 2mg/ml；Will be long Degree 20mm, the PTMC three-dimensional network polymer bar (its weight is 150mg) of diameter 3mm are placed in drug solution In, take out after 7 days, after placing 1 day naturally, constant weight is dried under vacuum to, surface spraying thickness is 0.5mm polytrimethylene carbonic acid Ester, drying obtains the Biodegradable slowly released and controlled-drug delivery system that drug loading is 20mg gestodene to constant weight.
Embodiment 4
In the present embodiment, Biodegradable slowly released and controlled-drug delivery system and preparation method thereof is as follows：
Precise 100mg gestodene is dissolved in 50ml chloroforms, and configuration concentration is the drug solution of 2mg/ml；Will be long Degree 20mm, external diameter 3mm, internal diameter are put for the PTMC three-dimensional network polymer pipe (its weight is 80mg) of 2mm In drug solution, take out after 7 days, after placing 1 day naturally, be dried under vacuum to constant weight, obtain drug loading for 10mg gestodene Biodegradable slowly released and controlled-drug delivery system.
Embodiment 5
In the present embodiment, Biodegradable slowly released and controlled-drug delivery system and preparation method thereof is as follows：
Precise 150mg ibuprofen is dissolved in 50ml chloroforms, and configuration concentration is the drug solution of 3mg/ml；By particle diameter The PTMC three-dimensional network polymer beads and polycaprolactone three-dimensional network for being respectively 50mg for 2mm, weight gather Polymer beads are placed in drug solution, are taken out after 7 days, after placing 1 day naturally, constant weight are dried under vacuum to, loaded on polycaprolactone glue It is intracapsular, obtain the Biodegradable slowly released and controlled-drug delivery system that drug loading is 16mg ibuprofen.
Embodiment 6
The Biodegradable slowly released and controlled-drug delivery system that embodiment 1 is obtained is some using deionized water and washes of absolute alcohol It is secondary, to remove the medicine for being enriched in system surfaces.Dried Biodegradable slowly released and controlled-drug delivery system is soaked in into 20ml to steam Distilled water, the constant temperature shaking under the conditions of 37 ± 1 DEG C, the frequency that shakes changed a solution per 24 hours for 65 beats/min, used high performance liquid chromatography Medicament contg in instrument test solution.Pharmaceutical release time 16 days, rate of release is about 120 micro- grams/day, as a result sees Fig. 2.
Figure it is seen that the Biodegradable slowly released and controlled-drug delivery system drug release effect that embodiment 1 is obtained is substantially, can be with The slow release to gestodene is realized, and later stage release tends to be steady, the performance with good sustained and controlled release medicament.
Embodiment result shows, Biodegradable slowly released and controlled-drug delivery system prepared by the present invention, process is simple, it is easy to grasp Make, the drug loading of drug-supplying system can pass through the parameters such as shape, size and the liquor strength of change carrier material product and realize.This is The effect that system is put with good biodegradability, biocompatibility and medicine sustained and controlled release, in organizational project and medicine Slow release field have higher application prospect, can be used for operation suture thread, Antiadhesive film, tissue engineering bracket, subcutaneous implant, Contraception implants, transdermal or inhalation disease prevention and treatment etc..

Claims (10)

1. a kind of Biodegradable slowly released and controlled-drug delivery system, it is characterised in that the system is with one or more biodegradations Type three-dimensional network polymer or Biodegradable cross-linked elastomer are pharmaceutical carrier, and the drug weight content in system is more than 0 To 50%.
2. according to the Biodegradable slowly released and controlled-drug delivery system described in claim 1, it is characterised in that the drug weight in system Preferred content is 10~20%.
3. according to the Biodegradable slowly released and controlled-drug delivery system described in claim 1, it is characterised in that medicine is amcinonide It is thing, anti-inflammatory analgetic class medicine, antiallergic class medicine, antifertility class medicine, antitumor class medicine, anti-senile dementia class medicine, anti- Schizophrenia class medicine, anti-infection drug, immunomodulating class medicine, antiproliferative pharmaceutical, neuroleptic and neurasthenia treating class Medicine or polypeptide protein and vaccine bio-pharmaceutical.
4. according to the Biodegradable slowly released and controlled-drug delivery system described in claim 1, it is characterised in that pharmaceutical carrier article shape Variation, using wire, bar-shaped, tubulose, lamellar, membranaceous, graininess, powder, weaving object, solid or irregular shape Shape body.
5. according to the Biodegradable slowly released and controlled-drug delivery system described in claim 1, it is characterised in that Biodegradable three dimensional network Network polymer is Acetic acid, hydroxy-, bimol. cyclic ester, L- lactides, DL- lactides, beta-propiolactone, (R, S)-Alpha-Methyl -- propiolactone, 3- methyl-β-the third Lactone, β-benzyloxycarbonyl group-beta-propiolactone, beta-butyrolactone, gamma-butyrolacton, α-bromo- gamma-butyrolacton, alpha-methylene-γ-Ding Nei Ester, (R) -3- hydroxy-gamma-butyrolactones, (R)-(-) -4- methylol butyrolactone, (S)-(+) -4- methylol butyrolactone, (S) - (-)-Alpha-hydroxy-gamma-butyrolacton, (S) -3- hydroxy-gamma-butyrolactones, DL- Alpha-hydroxies-beta, beta-dimethyl-gamma-butyrolacton, δ-penta Lactone, Beta-methyl-δ-valerolactone, (R) -4- methyl-δ-valerolactone, DL- Beta-methyls-beta-hydroxy-δ-valerolactone, (R) -5- first Base-δ-valerolactone, gamma-valerolactone, 6-caprolactone, δ-caprolactone, γ-hexalactone, 5- hydroxyl caprolactones, 3- methyl -4- oxos - 6- caprolactones, 3- methyl-epsilon-caprolactones, 4- methyl-epsilon-caprolactones, 4- ethyl-s-caprolactones, 4- propyl group -6-caprolactone, 5- first Base -6-caprolactone, 6- methyl-epsilon-caprolactones, γ-heptalactone, 7- methyl heptalactones；γ-octalactone, δ-octalactone, 8- methyl Caprylolactone, 4- hydroxy-3-methyls-caprylolactone, 1,4- caprylolactones, nonyl lactone, δ-nonalactone, γ-decalactone, δ-decalactone, ε-decalactone, 4- hydroxyls undecanoic acid-gamma lactone, δ-dodecalactone, γ-dodecalactone, 12- methyl-dodecalactone, 2- methylenes Base -4- oxo -12- dodecalactones, trimethylene carbonate, 5- benzyloxy trimethylene carbonates, the methylene of 5- benzyloxycarbonyl groups three Base carbonic ester, 5- allyloxy trimethylene carbonates, 5- methyl -5- benzyloxycarbonyl group trimethylene carbonates, 5- ethyl -5- hydroxyls Methyl trimethylene carbonate, 5- ethyl -5- phenyl trimethylene carbonates, 5- ethyl -5- butyl trimethylene carbonates, 2, The propargyl oxygen carbonyl three of 2- dimethyltrimethylene carbonates, 2- ethoxycarbonyl-2-methyl trimethylene carbonates, 2- methyl -2- Carbonate, 2- methyl -2- allyloxycarbonyl trimethylene carbonates, 2- methyl -2- Cortex Cinnamomi acyl-oxygen methyl trimethylenes Carbonic ester, 2- ethyl -2- Cortex Cinnamomi acyl-oxygen methyl trimethylene carbonates, 2,4- dioxo spiros [5.5] hendecane -3- ketone, 1- second Thiazolinyl -2,4- dioxo spiros [5.5] hendecane -3- ketone, 1,3- dioxolan-2-ones, 1,4- dioxane-2-ketones, 5- benzyloxies Methyl isophthalic acid, 4- dioxane-2-ketones, 1,5- Dioxepane -2- ketone, caprolactam, N- acetyl caprolactams, N- vinyls Caprolactam, DL- aminocaproic lactams, 3- inferior pentenyl -4- butyrolactams, N- bromine caprolactams, N- methyl caprolactam, heptan Lactams, (±)-alpha-amido-epsilon-caprolactams, morpholine -2,5- diketone, 3- methyl morpholine -2,5- diketone, 3- (benzyloxycarbonyl group second Base)-morpholine -2,5- diketone, (3S) -3- (benzyloxycarbonyl-methyl) morpholine -2,5- diketone, (3S, 6RS) -3- (benzyloxycarbonyl group first Base) -6- Methyl-morpholine -2,5- diketone, (3s, 6RS) -3- [4- (benzyloxycarbonyl amino) butyl] -6- Methyl-morpholines -2,5- two Ketone, (3S, 6RS) -3- methylol -6- Methyl-morpholines -2,5- diketone thio to methoxybenzyl, 3-N- benzyloxycarbonyl group lysyl-s - Morpholine -2,5- diketone, 6- isopropyls-morpholine -2,5- diketone, 6- isopropyl -3- Methyl-morpholine -2,5- diketone, maleic anhydride, Succinic anhydride, dimethyl succinic acid acid anhydride, 2- methylene-succinic anhydride, tetrafluoro succinic anhydride, glutaric anhydride, 3,3- tetramethylenes penta Dicarboxylic anhydride, 3,3- dimethylated pentanedioic acid acid anhydrides, 2,2- dimethylated pentanedioic acid acid anhydrides, 3- ethyl -3- methylglutaric acid acid anhydrides, hexafluoro 1,3-propanedicarboxylic acid Acid anhydride, adipic anhydride, sebacic anhydride, N- carboxyl-L-Alanine-ring inner-acid anhydrides, 2- methoxyl group -2- oxygen -1,3,2- dioxy phosphorus heterocycles Pentane, 2- ethyoxyl -2- oxygen -1,3,2- dioxaphospholane, 2- chloroethoxy -2- oxygen -1,3,2- dioxaphospholane, The chloro- 2- oxygen -1,3,2- dioxaphospholane of 2-, the propargyl epoxide -2- oxygen -1,3,2- dioxaphospholane of 2-, 5,5- diformazans Base -2- oxygen -1,3,2- dioxaphospholane, the chloro- 1,3,2- dioxaphosphorinanes -2- ketone of 5,5- dimethyl -2-, ethylidene Ethyl phosphonic acid ester EEP, ethylidene isobutyl group phosphate ester EIBP, ethylidene 1-isobutyl-3,5-dimethylhexylphosphoric acid ELP, ethylidene octadecyl phosphorus One or more in the cross-linked homopolymer or cross-linked copolymer of acid esters ESP and its derivant；
Biodegradable cross-linked elastomer be the network polyester of polynary aromatic acid and polycaprolactone glycol, poly- decanedioic acid glyceride, Poly- citric acid ethohexadiol ester, poly- decanedioic acid-ethylene glycol-glyceride, hydroxy alkanoic acid are modified the acid of poly- hydroxy alkyl, Polyethylene Glycol/poly- Terephthaldehyde's acrylic block copolymers, polybutylene terephthalate (PBT)-co- polycyclohexylene diformazan alcohol ester-b- Polyethylene Glycol, polyether ester amides, poly- peptide, poe, thermoplastic starch-based bioelastomer, thermosetting polyester elastomer, heat One or more in curable polyurethane elastomer, thermo-set polyether ester elastomer.
6. the preparation method of the Biodegradable slowly released and controlled-drug delivery system described in a kind of claim 1, it is characterised in that using molten Prepared by swollen method, comprise the steps：
(1) medicine is dissolved in into organic solvent, the controllable drug solution of compound concentration；
(2) pharmaceutical carrier product is placed in drug solution, is sufficiently stirred for, using the swelling character of pharmaceutical carrier by drug solution Absorb to support material internal；
(3) organic solvent is removed, obtains Biodegradable slowly released and controlled-drug delivery system.
7. according to the preparation method of the Biodegradable slowly released and controlled-drug delivery system described in claim 6, it is characterised in that according to need To carry out face coat to Biodegradable slowly released and controlled-drug delivery system, coating composition be Acetic acid, hydroxy-, bimol. cyclic ester, L- lactides, DL- lactides, Beta-propiolactone, (R, S)-Alpha-Methyl -- propiolactone, 3- methyl-ss-propiolactones, β-benzyloxycarbonyl group-beta-propiolactone, beta-butyrolactone, Gamma-butyrolacton, α-bromo- gamma-butyrolacton, alpha-methylene-gamma-butyrolactone, (R) -3- hydroxy-gamma-butyrolactones, (R)-(-) -4- hydroxyls Methylbutyrolactone, (S)-(+) -4- methylol butyrolactone, (S)-(-)-Alpha-hydroxy-gamma-butyrolacton, (S) -3- hydroxyl-γ-Ding Nei In ester, DL- Alpha-hydroxies-beta, beta-dimethyl-gamma-butyrolacton, δ-valerolactone, Beta-methyl-δ-valerolactone, (R) -4- methyl-δ-penta Ester, DL- Beta-methyls-beta-hydroxy-δ-valerolactone, (R) -5- methyl-δ-valerolactone, gamma-valerolactone, 6-caprolactone, δ-caprolactone, γ-hexalactone, 5- hydroxyl caprolactones, 3- methyl -4- oxo -6- caprolactones, 3- methyl-epsilon-caprolactones, 4- methyl-ε-oneself in Ester, 4- ethyl-s-caprolactones, 4- propyl group -6-caprolactone, 5- methyl-epsilon-caprolactones, 6- methyl-epsilon-caprolactones, γ-heptalactone, 7- methyl heptalactones；γ-octalactone, δ-octalactone, 8- methyl caprylolactones, 4- hydroxy-3-methyls-caprylolactone, 1,4- caprylolactones, In nonyl lactone, δ-nonalactone, γ-decalactone, δ-decalactone, ε-decalactone, 4- hydroxyls undecanoic acid-gamma lactone, δ-ten two Ester, γ-dodecalactone, 12- methyl-dodecalactone, 2- methylene -4- oxo -12- dodecalactones, trimethylene carbonate, 5- Benzyloxy trimethylene carbonate, 5- benzyloxycarbonyl group trimethylene carbonates, 5- allyloxy trimethylene carbonates, 5- first Base -5- benzyloxycarbonyl group trimethylene carbonates, 5- ethyl -5- methylol trimethylene carbonates, the methylene of 5- ethyl -5- phenyl three Base carbonic ester, 5- ethyl -5- butyl trimethylene carbonates, 2,2- dimethyltrimethylene carbonates, 2- carbethoxyl group -2- first The propargyl oxygen carbonyl trimethylene carbonate of base trimethylene carbonate, 2- methyl -2-, the methylene of 2- methyl -2- allyloxycarbonyls three Base carbonic ester, 2- methyl -2- Cortex Cinnamomi acyl-oxygen methyl trimethylene carbonates, 2- ethyl -2- Cortex Cinnamomi acyl-oxygen methyl trimethylene carbon Acid esters, 2,4- dioxo spiros [5.5] hendecane -3- ketone, 1- vinyl -2,4- dioxo spiros [5.5] hendecane -3- ketone, 1,3- Dioxolan-2-one, 1,4- dioxane-2-ketones, 5- benzyloxymethyl -1,4- dioxane-2-ketones, 1,5- dioxa cycloheptyls Alkane -2- ketone, caprolactam, N- acetyl caprolactams, N- caprolactams, DL- aminocaproic lactams, 3- inferior pentenyls - 4- butyrolactams, N- bromine caprolactams, N- methyl caprolactam, oenantholcatam, (±)-alpha-amido-epsilon-caprolactams, morpholine- 2,5- diketone, 3- methyl morpholine -2,5- diketone, 3- (benzyloxycarbonyl group ethyl)-morpholine -2,5- diketone, (3S) -3- (benzyloxycarbonyl groups Methyl) morpholine -2,5- diketone, (3S, 6RS) -3- (benzyloxycarbonyl-methyl) -6- Methyl-morpholine -2,5- diketone, (3s, 6RS) -3- [4- (benzyloxycarbonyl amino) butyl] -6- Methyl-morpholine -2,5- diketone, (3S, 6RS) -3- to the thio methylol of methoxybenzyl - 6- Methyl-morpholine -2,5- diketone, 3-N- benzyloxycarbonyl groups lysyl--morpholine -2,5- diketone, 6- isopropyls-morpholine -2,5- bis- Ketone, 6- isopropyl -3- Methyl-morpholine -2,5- diketone, maleic anhydride, succinic anhydride, dimethyl succinic acid acid anhydride, 2- methylene-fourth two Anhydride, tetrafluoro succinic anhydride, glutaric anhydride, 3,3- tetramethyleneglutaric acid acid anhydrides, 3,3- dimethylated pentanedioic acid acid anhydrides, 2,2- dimethyl Glutaric anhydride, 3- ethyl -3- methylglutaric acid acid anhydrides, hexafluoroglutaric anhydride, adipic anhydride, sebacic anhydride, N- carboxyls the third ammonia of-L- Acid-ring inner-acid anhydride, 2- methoxyl group -2- oxygen -1,3,2- dioxaphospholane, 2- ethyoxyl -2- oxygen -1,3,2- dioxy phosphorus heterocycles Pentane, 2- chloroethoxy -2- oxygen -1,3,2- dioxaphospholane, the chloro- 2- oxygen -1,3,2- dioxaphospholane of 2-, 2- alkynes Propoxyl group -2- oxygen -1,3,2- dioxaphospholane, 5,5- dimethyl -2- oxygen -1,3,2- dioxaphospholane, 5,5- bis- The chloro- 1,3,2- dioxaphosphorinanes -2- ketone of methyl -2-, ethylidene ethyl phosphonic acid ester EEP, ethylidene isobutyl group phosphate ester Homopolymer or the copolymerization of EIBP, ethylidene 1-isobutyl-3,5-dimethylhexylphosphoric acid ELP, ethylidene octadecyl phosphate ester ESP and its derivant Thing one or more, coating layer thickness be below 2mm；Or, Biodegradable slowly released and controlled-drug delivery system is loaded on into capsule It is interior.
8. according to the preparation method of the Biodegradable slowly released and controlled-drug delivery system described in claim 6, it is characterised in that step (1) in, drug solution concentration is controllable, and drug level is preferably 1~10mg/ml.
9. according to the preparation method of the Biodegradable slowly released and controlled-drug delivery system described in claim 6, it is characterised in that medicine is carried The shape and size of body is arbitrarily adjusted, and drug loading is controllable therewith.
10. the application of the Biodegradable slowly released and controlled-drug delivery system described in a kind of claim 1, it is characterised in that the system is used In operation suture thread, Antiadhesive film, tissue engineering bracket, subcutaneous implant, contraception implants, transdermal or inhalation.
CN201710084574.5A 2017-02-16 2017-02-16 Biodegradable slow/controlled-release drug delivery system and preparation method thereof Pending CN106667897A (en)

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CN113117130A (en) * 2021-01-13 2021-07-16 海南建科药业有限公司 Surface treatment method for medical operation line

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