CN108434506A - A kind of expandable sponges, the Preparation method and use of load nano controlled-release drug micelles - Google Patents
A kind of expandable sponges, the Preparation method and use of load nano controlled-release drug micelles Download PDFInfo
- Publication number
- CN108434506A CN108434506A CN201810389466.3A CN201810389466A CN108434506A CN 108434506 A CN108434506 A CN 108434506A CN 201810389466 A CN201810389466 A CN 201810389466A CN 108434506 A CN108434506 A CN 108434506A
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- CN
- China
- Prior art keywords
- release drug
- nano controlled
- expandable sponges
- drug micelles
- micelles
- 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.)
- Granted
Links
- 239000003814 drug Substances 0.000 title claims abstract description 79
- 229940079593 drug Drugs 0.000 title claims abstract description 75
- 238000013270 controlled release Methods 0.000 title claims abstract description 61
- 239000000693 micelle Substances 0.000 title claims abstract description 55
- 238000002360 preparation method Methods 0.000 title claims abstract description 11
- 230000002439 hemostatic effect Effects 0.000 claims abstract description 11
- 239000007788 liquid Substances 0.000 claims description 27
- 239000000243 solution Substances 0.000 claims description 21
- 238000003756 stirring Methods 0.000 claims description 21
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical group C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 14
- 229910021642 ultra pure water Inorganic materials 0.000 claims description 14
- 239000012498 ultrapure water Substances 0.000 claims description 14
- 229920000642 polymer Polymers 0.000 claims description 13
- 229920002451 polyvinyl alcohol Polymers 0.000 claims description 13
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 12
- 230000002209 hydrophobic effect Effects 0.000 claims description 12
- 239000003960 organic solvent Substances 0.000 claims description 12
- 230000006835 compression Effects 0.000 claims description 11
- 238000007906 compression Methods 0.000 claims description 11
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 9
- 229920002463 poly(p-dioxanone) polymer Polymers 0.000 claims description 9
- AOJJSUZBOXZQNB-TZSSRYMLSA-N Doxorubicin Chemical compound O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(=O)CO)[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1 AOJJSUZBOXZQNB-TZSSRYMLSA-N 0.000 claims description 8
- 235000010413 sodium alginate Nutrition 0.000 claims description 8
- 238000000034 method Methods 0.000 claims description 7
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 7
- IXPNQXFRVYWDDI-UHFFFAOYSA-N 1-methyl-2,4-dioxo-1,3-diazinane-5-carboximidamide Chemical compound CN1CC(C(N)=N)C(=O)NC1=O IXPNQXFRVYWDDI-UHFFFAOYSA-N 0.000 claims description 6
- SXRSQZLOMIGNAQ-UHFFFAOYSA-N Glutaraldehyde Chemical compound O=CCCCC=O SXRSQZLOMIGNAQ-UHFFFAOYSA-N 0.000 claims description 6
- RCEAADKTGXTDOA-UHFFFAOYSA-N OS(O)(=O)=O.CCCCCCCCCCCC[Na] Chemical compound OS(O)(=O)=O.CCCCCCCCCCCC[Na] RCEAADKTGXTDOA-UHFFFAOYSA-N 0.000 claims description 6
- 239000002202 Polyethylene glycol Substances 0.000 claims description 6
- 239000007864 aqueous solution Substances 0.000 claims description 6
- 229920001400 block copolymer Polymers 0.000 claims description 6
- 238000001523 electrospinning Methods 0.000 claims description 6
- 229920001427 mPEG Polymers 0.000 claims description 6
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 6
- 229920001432 poly(L-lactide) Polymers 0.000 claims description 6
- 229920001223 polyethylene glycol Polymers 0.000 claims description 6
- 229940005550 sodium alginate Drugs 0.000 claims description 6
- 239000000661 sodium alginate Substances 0.000 claims description 6
- 239000002904 solvent Substances 0.000 claims description 6
- 238000010792 warming Methods 0.000 claims description 6
- 229920000747 poly(lactic acid) Polymers 0.000 claims description 5
- XDXDZDZNSLXDNA-TZNDIEGXSA-N Idarubicin Chemical compound C1[C@H](N)[C@H](O)[C@H](C)O[C@H]1O[C@@H]1C2=C(O)C(C(=O)C3=CC=CC=C3C3=O)=C3C(O)=C2C[C@@](O)(C(C)=O)C1 XDXDZDZNSLXDNA-TZNDIEGXSA-N 0.000 claims description 4
- XDXDZDZNSLXDNA-UHFFFAOYSA-N Idarubicin Natural products C1C(N)C(O)C(C)OC1OC1C2=C(O)C(C(=O)C3=CC=CC=C3C3=O)=C3C(O)=C2CC(O)(C(C)=O)C1 XDXDZDZNSLXDNA-UHFFFAOYSA-N 0.000 claims description 4
- 229940009456 adriamycin Drugs 0.000 claims description 4
- 150000002148 esters Chemical class 0.000 claims description 4
- 229960000908 idarubicin Drugs 0.000 claims description 4
- RKDVKSZUMVYZHH-UHFFFAOYSA-N 1,4-dioxane-2,5-dione Chemical compound O=C1COC(=O)CO1 RKDVKSZUMVYZHH-UHFFFAOYSA-N 0.000 claims description 3
- JVTAAEKCZFNVCJ-REOHCLBHSA-N L-lactic acid Chemical compound C[C@H](O)C(O)=O JVTAAEKCZFNVCJ-REOHCLBHSA-N 0.000 claims description 3
- JJTUDXZGHPGLLC-UHFFFAOYSA-N lactide Chemical compound CC1OC(=O)C(C)OC1=O JJTUDXZGHPGLLC-UHFFFAOYSA-N 0.000 claims description 3
- 229920000382 poly(ethylene glycol) methyl ether-block-poly(L-lactide-co-glycolide) Polymers 0.000 claims description 3
- 229920001606 poly(lactic acid-co-glycolic acid) Polymers 0.000 claims description 3
- 239000000622 polydioxanone Substances 0.000 claims description 3
- 239000004626 polylactic acid Substances 0.000 claims description 3
- 239000003643 water by type Substances 0.000 claims description 3
- 229920001577 copolymer Polymers 0.000 claims description 2
- 238000001704 evaporation Methods 0.000 claims description 2
- 230000008020 evaporation Effects 0.000 claims description 2
- JBFHTYHTHYHCDJ-UHFFFAOYSA-N gamma-caprolactone Chemical compound CCC1CCC(=O)O1 JBFHTYHTHYHCDJ-UHFFFAOYSA-N 0.000 claims description 2
- 239000003292 glue Substances 0.000 claims description 2
- ATHHXGZTWNVVOU-UHFFFAOYSA-N N-methylformamide Chemical compound CNC=O ATHHXGZTWNVVOU-UHFFFAOYSA-N 0.000 claims 2
- 230000023597 hemostasis Effects 0.000 abstract description 5
- 239000000463 material Substances 0.000 abstract description 3
- 238000010382 chemical cross-linking Methods 0.000 abstract description 2
- 229940126534 drug product Drugs 0.000 abstract description 2
- 239000000825 pharmaceutical preparation Substances 0.000 abstract description 2
- 239000002861 polymer material Substances 0.000 abstract description 2
- 239000004372 Polyvinyl alcohol Substances 0.000 description 11
- 235000013339 cereals Nutrition 0.000 description 7
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 4
- 210000001331 nose Anatomy 0.000 description 4
- 238000000643 oven drying Methods 0.000 description 4
- 229910052708 sodium Inorganic materials 0.000 description 4
- 239000011734 sodium Substances 0.000 description 4
- 235000010443 alginic acid Nutrition 0.000 description 3
- 229920000615 alginic acid Polymers 0.000 description 3
- 150000004781 alginic acids Chemical class 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 238000005516 engineering process Methods 0.000 description 2
- OKJPEAGHQZHRQV-UHFFFAOYSA-N iodoform Chemical compound IC(I)I OKJPEAGHQZHRQV-UHFFFAOYSA-N 0.000 description 2
- 210000003928 nasal cavity Anatomy 0.000 description 2
- 238000005507 spraying Methods 0.000 description 2
- 238000013268 sustained release Methods 0.000 description 2
- 239000012730 sustained-release form Substances 0.000 description 2
- XBBVURRQGJPTHH-UHFFFAOYSA-N 2-hydroxyacetic acid;2-hydroxypropanoic acid Chemical compound OCC(O)=O.CC(O)C(O)=O XBBVURRQGJPTHH-UHFFFAOYSA-N 0.000 description 1
- 241001474374 Blennius Species 0.000 description 1
- 229920001661 Chitosan Polymers 0.000 description 1
- 208000032843 Hemorrhage Diseases 0.000 description 1
- 240000007594 Oryza sativa Species 0.000 description 1
- 235000007164 Oryza sativa Nutrition 0.000 description 1
- DHKHKXVYLBGOIT-UHFFFAOYSA-N acetaldehyde Diethyl Acetal Natural products CCOC(C)OCC DHKHKXVYLBGOIT-UHFFFAOYSA-N 0.000 description 1
- 150000001241 acetals Chemical class 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000033228 biological regulation Effects 0.000 description 1
- 230000000740 bleeding effect Effects 0.000 description 1
- 208000001780 epistaxis Diseases 0.000 description 1
- 239000004744 fabric Substances 0.000 description 1
- 238000004108 freeze drying Methods 0.000 description 1
- 230000008595 infiltration Effects 0.000 description 1
- 238000001764 infiltration Methods 0.000 description 1
- 239000011806 microball Substances 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 208000011309 nasal bleeding Diseases 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 235000009566 rice Nutrition 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 230000017423 tissue regeneration Effects 0.000 description 1
- 229940099259 vaseline Drugs 0.000 description 1
- 229920002554 vinyl polymer Polymers 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
- 230000037314 wound repair Effects 0.000 description 1
- PAPBSGBWRJIAAV-UHFFFAOYSA-N ε-Caprolactone Chemical compound O=C1CCCCCO1 PAPBSGBWRJIAAV-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- 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
- A61L15/00—Chemical aspects of, or use of materials for, bandages, dressings or absorbent pads
- A61L15/16—Bandages, dressings or absorbent pads for physiological fluids such as urine or blood, e.g. sanitary towels, tampons
- A61L15/22—Bandages, dressings or absorbent pads for physiological fluids such as urine or blood, e.g. sanitary towels, tampons containing macromolecular materials
- A61L15/26—Macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds; Derivatives thereof
-
- 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
- A61L15/00—Chemical aspects of, or use of materials for, bandages, dressings or absorbent pads
- A61L15/16—Bandages, dressings or absorbent pads for physiological fluids such as urine or blood, e.g. sanitary towels, tampons
- A61L15/20—Bandages, dressings or absorbent pads for physiological fluids such as urine or blood, e.g. sanitary towels, tampons containing organic materials
-
- 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
- A61L15/00—Chemical aspects of, or use of materials for, bandages, dressings or absorbent pads
- A61L15/16—Bandages, dressings or absorbent pads for physiological fluids such as urine or blood, e.g. sanitary towels, tampons
- A61L15/22—Bandages, dressings or absorbent pads for physiological fluids such as urine or blood, e.g. sanitary towels, tampons containing macromolecular materials
- A61L15/24—Macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds; Derivatives thereof
-
- 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
- A61L15/00—Chemical aspects of, or use of materials for, bandages, dressings or absorbent pads
- A61L15/16—Bandages, dressings or absorbent pads for physiological fluids such as urine or blood, e.g. sanitary towels, tampons
- A61L15/22—Bandages, dressings or absorbent pads for physiological fluids such as urine or blood, e.g. sanitary towels, tampons containing macromolecular materials
- A61L15/28—Polysaccharides or their derivatives
-
- 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
- A61L15/00—Chemical aspects of, or use of materials for, bandages, dressings or absorbent pads
- A61L15/16—Bandages, dressings or absorbent pads for physiological fluids such as urine or blood, e.g. sanitary towels, tampons
- A61L15/42—Use of materials characterised by their function or physical properties
-
- 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
- A61L15/00—Chemical aspects of, or use of materials for, bandages, dressings or absorbent pads
- A61L15/16—Bandages, dressings or absorbent pads for physiological fluids such as urine or blood, e.g. sanitary towels, tampons
- A61L15/42—Use of materials characterised by their function or physical properties
- A61L15/425—Porous materials, e.g. foams or sponges
-
- 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
- A61L15/00—Chemical aspects of, or use of materials for, bandages, dressings or absorbent pads
- A61L15/16—Bandages, dressings or absorbent pads for physiological fluids such as urine or blood, e.g. sanitary towels, tampons
- A61L15/42—Use of materials characterised by their function or physical properties
- A61L15/44—Medicaments
-
- 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
- A61L2300/40—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a specific therapeutic activity or mode of action
- A61L2300/412—Tissue-regenerating or healing or proliferative agents
-
- 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
- A61L2300/60—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a special physical form
- A61L2300/602—Type of release, e.g. controlled, sustained, slow
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L2400/00—Materials characterised by their function or physical properties
- A61L2400/04—Materials for stopping bleeding
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L2400/00—Materials characterised by their function or physical properties
- A61L2400/12—Nanosized materials, e.g. nanofibres, nanoparticles, nanowires, nanotubes; Nanostructured surfaces
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Epidemiology (AREA)
- Hematology (AREA)
- Engineering & Computer Science (AREA)
- Materials Engineering (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Dispersion Chemistry (AREA)
- Medicinal Preparation (AREA)
Abstract
The invention belongs to hemostatic material technical fields, it is related to biological medical polymer material and chemical crosslinking sponge and modified field, more particularly to a kind of expandable sponges, the Preparation method and use of load nano controlled-release drug micelles, including expandable sponges ontology, contain load nano controlled-release drug micelles in expandable sponges ontology, sponge of the present invention has hemostasis and depot drug product slow-release function, with important application prospects in terms of nose cavity hemostatic and promotion surface of a wound function reparation.
Description
Technical field
The invention belongs to hemostatic material technical fields, are related to biological medical polymer material and chemical crosslinking sponge and modification
Field, and in particular to a kind of expandable sponges, the Preparation method and use of load nano controlled-release drug micelles.
Background technology
Currently, clinical ear-nose-throat department is in nasal bleeding anthemorrhagic operation, majority using vaseline gauze cloth, gelfoam,
Iodoform gauze carries out hemostasis with packs.Some styptic sponges, such as gelfoam pass through the infiltration of nasal cavity liquid, can be rapid swollen
It is swollen, bleeding part is effectively oppressed, achievees the purpose that physics hemostasis by compression.But it if in nasal cavity parectasis, can make
At rhinostegnosis, cause patient and its unconformable symptom.Pioloform, polyvinyl acetal sponge has the energy for absorbing liquid well
Power, absorbency is up to 5-30 times, compared with traditional hemostatic material, hemostasis, expansion, the drawing of polyvinyl alcohol styptic sponge
The physical and chemical performances such as stretching, shrink, there are many advantages, and the factor, such sponge is in medical field, especially in nose cavity hemostatic
In field is widely used.
However, styptic sponge, after completing to stop blooding, the self performance of sponge also plays weight for the recovery of surface of a wound function
The effect wanted.For this reason, it may be necessary to after completing hemostatic function, the styptic sponge of the surface of a wound should be able to have better wound repair work(
Energy.Drug is directly added in existing patent CN104784738A discloses sponge at present, by the sustained release of sponge, to improve sea
Continuous comprehensive performance.In order to which the anthemorrhagic performance and chitosan microball carrying medicament (CN101590288A) that extend sponge carry out drug
The sponge of sustained release.
However, repairing field in nose cavity hemostatic and function, appoint so shortage is a kind of there is hemostatic function and regulation and control damaged part
The expandable sponges of tissue repair function.
Invention content
Insufficient in view of the prior art, the present invention provides a kind of expandable sponges of load nano controlled-release drug micelles, prepares
Method and purposes.
To achieve the goals above, the technical solution used in the present invention is:A kind of load nano controlled-release drug micelles
Expandable sponges, including expandable sponges ontology, which is characterized in that contain load nano controlled-release drug micelles in expandable sponges ontology.
A kind of preparation method of the expandable sponges of load nano controlled-release drug micelles, this method comprises the following steps:
(1) nano controlled-release drug micelles liquid is made
1-10mg amphipathic nature block polymers and 0.01-2mg hydrophobic drugs are dissolved in 1-5mL organic solvents be made it is poly-
Polymer solution is that 0.01-0.10mL/min instillation stir speed (S.S.)s are 400-2000rpm and capacity is the super of 10-100mL to drip speed
In pure water, then continue stirring 24-48h under 400-2000rpm rates, obtains containing grain size being 100- finally by evaporation solvent
The nano controlled-release drug micelles liquid of 260nm;
(2) compressed sponge is made
It takes the PVA of 1-5g to be dissolved in the ultra-pure water of 19mL-28.3mL, is configured to the aqueous solution of a concentration of 5%-15%, adds
Enter 1-5g sodium alginates and the lauryl sodium sulfate of 0.1-2.5g, 1-6h stirred under the conditions of 60-90 DEG C, 200-800rpm,
Temperature is down to 20-30 DEG C, and the hydrochloric acid solution of a concentration of 1mol/L of 2-20mL is added, and stir speed (S.S.) is controlled in 200-300rpm, stirred
Time control is mixed in 30-90min;A concentration of 50% glutaraldehyde solutions of 2-10g are added, stir speed (S.S.) is controlled in 200-300rpm,
Mixing time is controlled in 2-10min;35 DEG C -40 DEG C are warming up to, 1-5h is reacted;By gained sponge 1-2L ultrapure waters 3-5
It is secondary, suitable sponge will be cut and be put into mold, compressed sponge obtains compression times by 50-80 DEG C of dry 24-30h of baking oven
The compressed sponge that rate is 5-20 times;
(3) expandable sponges are made
By nano controlled-release drug micelles liquid obtained by step (1), the nano controlled-release medicine that mass concentration is 1%-10% is made
Object micellar liquid is humidity 20%-30% in setting air using electrospinning device, and voltage is (+15kV)~(+18kV),
(- 0.5kV)~(- 1.5kV), receiver distance is 10-20cm, by 1-10mL nano controlled-release drug micelles solution, with 2-5mL/h
Rate promote, be sprayed on compressed sponge surface obtained by step (2), obtain the expandable sponges of load nano controlled-release drug micelles.
The amphipathic di-block copolymer is mPEG-b-PLLA, mPEG-b-PLGA, mPEG-b-PCL, mPEG-b-
PPDO, wherein mPEG is that molecular weight is the terminal methyl polyethylene glycol that number-average molecular weight is 500-5000, and PLLA is number-average molecular weight
Molecular weight is the poly- L-type polylactic acid of 5000-20000, and PLGA is that the poly (lactic acid-glycolic acid) that number-average molecular weight is 5000-20000 is total
The ratio of polymers, wherein glycolide and lactide is 70-80:30-20, PCL are the poly- ε-that number-average molecular weight is 5000-20000
Caprolactone, PPDO are the polydioxanone that number-average molecular weight is 5000-20000.
The hydrophobic drug is at least one of dipropium dipropionate ester, adriamycin and idarubicin.
The organic solvent be tetrahydrofuran, N,N-dimethylformamide, volume ratio be (1-3):1 tetrahydrofuran and N,
The mixed liquor of dinethylformamide.
The PVA is at least one of 1797 types, 1799 types, 1788 types, PVA-117 types, the sodium alginate viscosity
For 200 ± 20mPa.s.
A kind of purposes of the expandable sponges of load nano controlled-release drug micelles, which is characterized in that the sponge contains load and receives
Rice slow releasing pharmaceutical micella, is applied to nose cavity hemostatic.
Beneficial effects of the present invention:Sponge of the present invention has hemostasis and depot drug product slow-release function, in nose cavity hemostatic and rush
It is with important application prospects into surface of a wound function reparation aspect.
Description of the drawings
Fig. 1 be the present invention after freeze-drying, porous structure electronic scanner microscope figure;
Fig. 2 is average grain diameter of the present invention using the DLS nano controlled-release drug micelles measured;
Fig. 3 is after expandable sponges surface spraying nano controlled-release drug micelles of the present invention, the electron scanning of surface texture is micro-
Mirror figure;
Fig. 4 is medicament slow release curve graph of the present invention.
Specific implementation mode
As Figure 1-Figure 4, embodiment 1, a kind of expandable sponges of load nano controlled-release drug micelles, with following methods system
At:
(1) by 1mg amphipathic nature block polymers, 0.01 hydrophobic drug is dissolved in 1mL organic solvents that polymer is made is molten
Liquid is that 0.01mL/min is instilled in the ultra-pure water for the 10mL that stir speed (S.S.) is 400rpm, then is stirred for 24 hours in 400rpm in drop speed,
Solvent is evaporated, is obtained containing the nano controlled-release drug micelles liquid that grain size is 100nm,
The amphipathic di-block copolymer is mPEG-b-PLLA, wherein mPEG is that molecular weight is that number-average molecular weight is
500 terminal methyl polyethylene glycol, PLLA are the poly- L-type polylactic acid that number-average molecular weight molecular weight is 5000.
The hydrophobic drug is dipropium dipropionate ester.The organic solvent is tetrahydrofuran.
(2) it takes the PVA of 1g to be dissolved in the ultra-pure water of 19mLmL, is configured to a concentration of 5% aqueous solution, 1g alginic acids are added
The lauryl sodium sulfate of 0.1g is added in sodium.60 DEG C, 1h is stirred under the conditions of 200rpm.Temperature is down to 20 DEG C, and 2mL concentration is added
For the hydrochloric acid solution of 1mol/L, 200rpm, 30min are stirred, a concentration of 50% glutaraldehyde solutions of 2g, 200rpm stirrings is added
2min.35 DEG C are warming up to, 1h is reacted.By gained sponge 1L ultrapure water 3 times, suitable sponge will be cut and be put into mold,
After compression, in 50 DEG C of oven dryings for 24 hours, compressed sponge is obtained.The compression multiplying power of gained sponge is 5 times.
The PVA is 1797 types.The sodium alginate viscosity is 200 ± 20mPa.s.
(3) by nano controlled-release drug micelles liquid obtained by step (1), the nano controlled-release drug that mass concentration is 1% is made
Micellar liquid is humidity 20% in setting air using electrospinning device, and voltage is+18kV, -- 1.5kV, receiver distance
1mL nano controlled-release drug micelles solution is promoted rate with 2mL/h, is sprayed on compressed sponge table obtained by step (2) for 10cm
Face obtains a kind of expandable sponges of load nano controlled-release drug micelles.
A kind of embodiment 2, expandable sponges of load nano controlled-release drug micelles, is made of following methods:
(1) by 10mg amphipathic nature block polymers, 2mg hydrophobic drugs are dissolved in 5mL organic solvents that polymer is made is molten
Liquid is that 0.10mL/min is instilled in the ultra-pure water for the 100mL that stir speed (S.S.) is 2000rpm, then is stirred in 2000rpm in drop speed
48h evaporates solvent, obtains containing the nano controlled-release drug micelles liquid that grain size is 260nm,
The amphipathic di-block copolymer be mPEG-b-PCL wherein, it be number-average molecular weight is 5000 that mPEG, which is molecular weight,
Terminal methyl polyethylene glycol, PCL is the poly- 6-caprolactone that number-average molecular weight is 20000.
The hydrophobic drug is idarubicin.The organic solvent is that volume ratio is (1-3):1 tetrahydrofuran and N,
The mixed liquor of dinethylformamide.
(2) it takes the PVA of 5g to be dissolved in the ultra-pure water of 28.3mL, is configured to a concentration of 15% aqueous solution, 5g seaweed are added
The lauryl sodium sulfate of 2.5g is added in sour sodium.90 DEG C, 6h is stirred under the conditions of 800rpm.Temperature is down to 30 DEG C, and it is dense that 20mL is added
Degree is the hydrochloric acid solution of 1mol/L, stirs 300rpm, 90min, and a concentration of 50% glutaraldehyde solutions of 10g, 300rpm stirrings is added
10min.40 DEG C are warming up to, 5h is reacted.By gained sponge 2L ultrapure water 5 times, suitable sponge will be cut and be put into mold,
After compression, the 30h in 80 DEG C of oven dryings obtains compressed sponge.The compression multiplying power of gained sponge is 20 times.
The PVA is 1788 types and PVA-117 types.The sodium alginate viscosity is 200 ± 20mPa.s.
(3) by nano controlled-release drug micelles liquid obtained by step (1), the nano controlled-release drug that mass concentration is 10% is made
Micellar liquid is humidity 30% in setting air, voltage is (+15kV)~(- 0.5kV), receiver using electrospinning device
Distance is 20cm, and by 10mL nano controlled-release drug micelles solution, rate is promoted with 5mL/h, is sprayed on compression sea obtained by step (2)
Continuous surface obtains a kind of expandable sponges of load nano controlled-release drug micelles.
A kind of embodiment 3, expandable sponges of load nano controlled-release drug micelles, is made of following methods:
(1) by 5mg amphipathic nature block polymers, 1mg hydrophobic drugs are dissolved in 4mL organic solvents that polymer is made is molten
Liquid is that 0.05mL/min is instilled in the ultra-pure water for the 30mL that stir speed (S.S.) is 1000rpm, then is stirred in 1000rpm in drop speed
36h evaporates solvent, obtains containing the nano controlled-release drug micelles liquid that grain size is 105nm, gained nano controlled-release drug micelles liquid
Body, presentation is light blue, there is Tyndall effect, (as shown in Fig. 2, for using the average grain of the DLS nano controlled-release drug micelles measured
Diameter)
The amphipathic di-block copolymer is mPEG-b-PPDO, wherein mPEG is that molecular weight is that number-average molecular weight is
3000 terminal methyl polyethylene glycol, PPDO are the polydioxanone that number-average molecular weight is 10000.
The hydrophobic drug is at least one of dipropium dipropionate ester, adriamycin, idarubicin etc..
The organic solvent is N,N-dimethylformamide.
(2) it takes the PVA of 2g to be dissolved in the ultra-pure water of 18mL, is configured to a concentration of 10% aqueous solution, 2g alginic acids are added
The lauryl sodium sulfate of 1g is added in sodium.70 DEG C, 4h is stirred under the conditions of 600rpm.Temperature is down to 25 DEG C, and it is a concentration of that 10mL is added
The hydrochloric acid solution of 1mol/L stirs 250rpm, 60min, and a concentration of 50% glutaraldehyde solutions of 5g are added, and 250rpm stirs 8min.
38 DEG C are warming up to, 3h is reacted.By gained sponge 1.5L ultrapure waters 4 times, suitable sponge will be cut and be put into mold, compressed
Afterwards, the 27h in 60 DEG C of oven dryings, obtains compressed sponge.The compression multiplying power of gained sponge is 10 times.
The PVA is at least one of PVA-117 types.The sodium alginate viscosity is 200 ± 20mPa.s.
(3) by nano controlled-release drug micelles liquid obtained by step (1), the nano controlled-release drug that mass concentration is 5% is made
Micellar liquid is humidity 25% in setting air using electrospinning device, and voltage is (+16kV), (- 1kV), receiver away from
5mL nano controlled-release drug micelles solution is promoted rate with 4mL/h, is sprayed on compressed sponge obtained by step (2) from for 15cm
Surface obtains a kind of expandable sponges of load nano controlled-release drug micelles.
Embodiment 4, a kind of expandable sponges of load nano controlled-release drug micelles, it is characterized in that by nano controlled-release drug micelles
It is constituted with expandable sponges.Preparation method, it is characterized in that being made of following methods:
(1) by 7mg amphipathic nature block polymers, 1.5mg hydrophobic drugs are dissolved in 4mL organic solvents that polymer is made is molten
Liquid is that 0.09mL/min is instilled in the ultra-pure water for the 50mL that stir speed (S.S.) is 1500rpm, then is stirred in 1200rpm in drop speed
38h evaporates solvent, obtains containing the nano controlled-release drug micelles liquid that grain size is 200nm,
The amphipathic di-block copolymer is mPEG-b-PLGA, wherein mPEG is that molecular weight is that number-average molecular weight is
4000 terminal methyl polyethylene glycol, PLGA are the polylactide glycolate copolymer that number-average molecular weight is 15000, wherein glycolide and
The ratio of lactide is 70:30.
The hydrophobic drug is adriamycin.
The organic solvent is tetrahydrofuran.
(2) it takes the PVA of 3g to be dissolved in the ultra-pure water of 22mL, is configured to a concentration of 12% aqueous solution, 4g alginic acids are added
The lauryl sodium sulfate of 0.5g is added in sodium.80 DEG C, 4h is stirred under the conditions of 600rpm.Temperature is down to 25 DEG C, and 10mL concentration is added
For the hydrochloric acid solution of 1mol/L, 280rpm, 70min are stirred, a concentration of 50% glutaraldehyde solutions of 5g, 220rpm stirrings is added
7min.39 DEG C are warming up to, 2h is reacted.By gained sponge 2L ultrapure water 5 times, suitable sponge will be cut and be put into mold,
After compression, in 80 DEG C of oven dryings for 24 hours, compressed sponge is obtained.The compression multiplying power of gained sponge is 12 times.
The PVA is 1799 types.The sodium alginate viscosity is 200 ± 20mPa.s.
(3) by nano controlled-release drug micelles liquid obtained by step (1), the nano controlled-release drug glue of mass concentration 5% is made
Beam liquid is humidity 20% in setting air using electrospinning device, and voltage is (+15kV), (- 0.5kV), receiver away from
10mL nano controlled-release drug micelles solution is promoted rate with 2mL/h, is sprayed on compressed sponge obtained by step (2) from for 10cm
Surface, obtain it is a kind of load nano controlled-release drug micelles expandable sponges (as shown in figure 3, for load nano controlled-release drug micelles
Expandable sponges surface spraying nano controlled-release drug micelles after, the electronic scanner microscope figure of surface texture).To the drug of sponge
Slow release effect is tested, the results showed that the medicament slow release time of the sponge was up to 30 days (as shown in Figure 4).
The basic principles, main features and advantages of the present invention have been shown and described above.The technology of the industry
Personnel are it should be appreciated that the present invention is not limited to the above embodiments, and the above embodiments and description only describe this
The principle of invention, without departing from the spirit and scope of the present invention, those ordinary skill in the art's simply changes
All it is within protection scope of the present invention with replacing.
Claims (7)
1. a kind of expandable sponges of load nano controlled-release drug micelles, including expandable sponges ontology, which is characterized in that expandable sponges
Contain load nano controlled-release drug micelles in ontology.
2. a kind of preparation method of the expandable sponges of load nano controlled-release drug micelles, this method comprises the following steps:
(1) nano controlled-release drug micelles liquid is made
1-10mg amphipathic nature block polymers and 0.01-2mg hydrophobic drugs are dissolved in 1-5mL organic solvents, polymer is made
Solution, with drip speed be 0.01-0.10mL/min instillation stir speed (S.S.) be 400-2000rpm and capacity for 10-100mL ultra-pure water
In, then continue stirring 24-48h under 400-2000rpm rates, it obtains containing grain size being 100- finally by evaporation solvent
The nano controlled-release drug micelles liquid of 260nm;
(2) compressed sponge is made
It takes the PVA of 1-5g to be dissolved in the ultra-pure water of 19mL-28.3mL, is configured to the aqueous solution of a concentration of 5%-15%, 1- is added
The lauryl sodium sulfate of 5g sodium alginates and 0.1-2.5g stirs 1-6h, temperature under the conditions of 60-90 DEG C, 200-800rpm
It is down to 20-30 DEG C, the hydrochloric acid solution of a concentration of 1mol/L of 2-20mL is added, stir speed (S.S.) is controlled in 200-300rpm, stirring
Between control in 30-90min;A concentration of 50% glutaraldehyde solutions of 2-10g are added, stir speed (S.S.) control is in 200-300rpm, stirring
Time control is in 2-10min;35 DEG C -40 DEG C are warming up to, 1-5h is reacted;It, will by gained sponge 1-2L ultrapure waters 3-5 times
It cuts suitable sponge and is put into mold, for compressed sponge by 50-80 DEG C of dry 24-30h of baking oven, it is 5- to obtain compression multiplying power
20 times of compressed sponge;
(3) expandable sponges are made
By nano controlled-release drug micelles liquid obtained by step (1), the nano controlled-release drug glue that mass concentration is 1%-10% is made
Beam liquid is humidity 20%-30% in setting air using electrospinning device, and voltage is (+15kV)~(+18kV), (-
0.5kV)~(- 1.5kV), receiver distance is 10-20cm, by 1-10mL nano controlled-release drug micelles solution, with 2-5mL/h's
Rate promotes, and is sprayed on compressed sponge surface obtained by step (2), obtains the expandable sponges of load nano controlled-release drug micelles.
3. a kind of preparation method of the expandable sponges of load nano controlled-release drug micelles as claimed in claim 2, feature exist
In, the amphipathic di-block copolymer be mPEG-b-PLLA, mPEG-b-PLGA, mPEG-b-PCL, mPEG-b-PPDO,
In, mPEG is that molecular weight is the terminal methyl polyethylene glycol that number-average molecular weight is 500-5000, and PLLA is number-average molecular weight molecular weight
For the poly- L-type polylactic acid of 5000-20000, PLGA is the polylactide glycolate copolymer that number-average molecular weight is 5000-20000,
The ratio of middle glycolide and lactide is 70-80:30-20, PCL are the poly- 6-caprolactone that number-average molecular weight is 5000-20000,
PPDO is the polydioxanone that number-average molecular weight is 5000-20000.
4. a kind of preparation method of the expandable sponges of load nano controlled-release drug micelles as claimed in claim 2, feature exist
In the hydrophobic drug is at least one of dipropium dipropionate ester, adriamycin and idarubicin.
5. a kind of preparation method of the expandable sponges of load nano controlled-release drug micelles as claimed in claim 2, feature exist
In, the organic solvent is tetrahydrofuran, n,N-Dimethylformamide, volume ratio are (1-3):1 tetrahydrofuran and N, N- bis-
The mixed liquor of methylformamide.
6. a kind of preparation method of the expandable sponges of load nano controlled-release drug micelles as claimed in claim 2, feature exist
In the PVA is at least one of 1797 types, 1799 types, 1788 types, PVA-117 types, and the sodium alginate viscosity is 200
±20mPa.s。
7. a kind of purposes of the expandable sponges of load nano controlled-release drug micelles, which is characterized in that the sponge contains load nanometer
Slow releasing pharmaceutical micella is applied to nose cavity hemostatic.
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