CN114471389A - Micro-fluidic preparation method and application of marine polymer microspheres - Google Patents
Micro-fluidic preparation method and application of marine polymer microspheres Download PDFInfo
- Publication number
- CN114471389A CN114471389A CN202210046308.4A CN202210046308A CN114471389A CN 114471389 A CN114471389 A CN 114471389A CN 202210046308 A CN202210046308 A CN 202210046308A CN 114471389 A CN114471389 A CN 114471389A
- Authority
- CN
- China
- Prior art keywords
- solution
- chitosan
- phase liquid
- microspheres
- micro
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
- 239000004005 microsphere Substances 0.000 title claims abstract description 119
- 229920000642 polymer Polymers 0.000 title claims abstract description 37
- 238000002360 preparation method Methods 0.000 title claims abstract description 25
- 239000007788 liquid Substances 0.000 claims abstract description 66
- 230000009471 action Effects 0.000 claims abstract description 21
- 238000010008 shearing Methods 0.000 claims abstract description 20
- 238000000034 method Methods 0.000 claims abstract description 19
- 239000003960 organic solvent Substances 0.000 claims abstract description 12
- 229920001661 Chitosan Polymers 0.000 claims description 158
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 57
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 24
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 24
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 18
- 235000010443 alginic acid Nutrition 0.000 claims description 17
- 229960001126 alginic acid Drugs 0.000 claims description 17
- 239000000783 alginic acid Substances 0.000 claims description 17
- 229920000615 alginic acid Polymers 0.000 claims description 17
- 150000004781 alginic acids Chemical class 0.000 claims description 17
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 14
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 claims description 12
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 claims description 11
- 239000003814 drug Substances 0.000 claims description 11
- WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 claims description 10
- ZCCIPPOKBCJFDN-UHFFFAOYSA-N calcium nitrate Chemical compound [Ca+2].[O-][N+]([O-])=O.[O-][N+]([O-])=O ZCCIPPOKBCJFDN-UHFFFAOYSA-N 0.000 claims description 10
- 229940079593 drug Drugs 0.000 claims description 10
- VCJMYUPGQJHHFU-UHFFFAOYSA-N iron(3+);trinitrate Chemical compound [Fe+3].[O-][N+]([O-])=O.[O-][N+]([O-])=O.[O-][N+]([O-])=O VCJMYUPGQJHHFU-UHFFFAOYSA-N 0.000 claims description 10
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 10
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 claims description 8
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 claims description 8
- 229910017053 inorganic salt Inorganic materials 0.000 claims description 8
- 229910052751 metal Inorganic materials 0.000 claims description 7
- 239000002184 metal Substances 0.000 claims description 7
- 239000002105 nanoparticle Substances 0.000 claims description 7
- 239000002253 acid Substances 0.000 claims description 6
- 239000003513 alkali Substances 0.000 claims description 6
- 239000001110 calcium chloride Substances 0.000 claims description 6
- 229910001628 calcium chloride Inorganic materials 0.000 claims description 6
- IEJIGPNLZYLLBP-UHFFFAOYSA-N dimethyl carbonate Chemical compound COC(=O)OC IEJIGPNLZYLLBP-UHFFFAOYSA-N 0.000 claims description 6
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 claims description 6
- 150000003839 salts Chemical class 0.000 claims description 6
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 5
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 claims description 5
- VSCWAEJMTAWNJL-UHFFFAOYSA-K aluminium trichloride Chemical compound Cl[Al](Cl)Cl VSCWAEJMTAWNJL-UHFFFAOYSA-K 0.000 claims description 5
- 229910021389 graphene Inorganic materials 0.000 claims description 5
- 229910017604 nitric acid Inorganic materials 0.000 claims description 5
- 239000002904 solvent Substances 0.000 claims description 5
- OSGAYBCDTDRGGQ-UHFFFAOYSA-L calcium sulfate Chemical compound [Ca+2].[O-]S([O-])(=O)=O OSGAYBCDTDRGGQ-UHFFFAOYSA-L 0.000 claims description 4
- SZVJSHCCFOBDDC-UHFFFAOYSA-N ferrosoferric oxide Chemical compound O=[Fe]O[Fe]O[Fe]=O SZVJSHCCFOBDDC-UHFFFAOYSA-N 0.000 claims description 4
- 229910052742 iron Inorganic materials 0.000 claims description 4
- 239000005543 nano-size silicon particle Substances 0.000 claims description 4
- 235000012239 silicon dioxide Nutrition 0.000 claims description 4
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 claims description 3
- 239000003463 adsorbent Substances 0.000 claims description 3
- -1 ferric dichloride Chemical compound 0.000 claims description 3
- 239000011790 ferrous sulphate Substances 0.000 claims description 3
- 235000003891 ferrous sulphate Nutrition 0.000 claims description 3
- 235000019253 formic acid Nutrition 0.000 claims description 3
- BAUYGSIQEAFULO-UHFFFAOYSA-L iron(2+) sulfate (anhydrous) Chemical compound [Fe+2].[O-]S([O-])(=O)=O BAUYGSIQEAFULO-UHFFFAOYSA-L 0.000 claims description 3
- 229910000359 iron(II) sulfate Inorganic materials 0.000 claims description 3
- 238000013268 sustained release Methods 0.000 claims description 3
- 239000012730 sustained-release form Substances 0.000 claims description 3
- BNGXYYYYKUGPPF-UHFFFAOYSA-M (3-methylphenyl)methyl-triphenylphosphanium;chloride Chemical compound [Cl-].CC1=CC=CC(C[P+](C=2C=CC=CC=2)(C=2C=CC=CC=2)C=2C=CC=CC=2)=C1 BNGXYYYYKUGPPF-UHFFFAOYSA-M 0.000 claims description 2
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 claims description 2
- UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 claims description 2
- CWYNVVGOOAEACU-UHFFFAOYSA-N Fe2+ Chemical compound [Fe+2] CWYNVVGOOAEACU-UHFFFAOYSA-N 0.000 claims description 2
- 229910002651 NO3 Inorganic materials 0.000 claims description 2
- NHNBFGGVMKEFGY-UHFFFAOYSA-N Nitrate Chemical compound [O-][N+]([O-])=O NHNBFGGVMKEFGY-UHFFFAOYSA-N 0.000 claims description 2
- 229910052782 aluminium Inorganic materials 0.000 claims description 2
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 claims description 2
- 239000011575 calcium Substances 0.000 claims description 2
- 229910052791 calcium Inorganic materials 0.000 claims description 2
- 125000004432 carbon atom Chemical group C* 0.000 claims description 2
- RBTARNINKXHZNM-UHFFFAOYSA-K iron trichloride Chemical compound Cl[Fe](Cl)Cl RBTARNINKXHZNM-UHFFFAOYSA-K 0.000 claims description 2
- RUTXIHLAWFEWGM-UHFFFAOYSA-H iron(3+) sulfate Chemical compound [Fe+3].[Fe+3].[O-]S([O-])(=O)=O.[O-]S([O-])(=O)=O.[O-]S([O-])(=O)=O RUTXIHLAWFEWGM-UHFFFAOYSA-H 0.000 claims description 2
- 229910000360 iron(III) sulfate Inorganic materials 0.000 claims description 2
- 239000003431 cross linking reagent Substances 0.000 abstract description 12
- 239000003995 emulsifying agent Substances 0.000 abstract description 10
- 238000010828 elution Methods 0.000 abstract description 5
- 239000002351 wastewater Substances 0.000 abstract description 3
- 230000001988 toxicity Effects 0.000 abstract description 2
- 231100000419 toxicity Toxicity 0.000 abstract description 2
- 239000000243 solution Substances 0.000 description 165
- 239000012071 phase Substances 0.000 description 70
- 239000008385 outer phase Substances 0.000 description 35
- PHTQWCKDNZKARW-UHFFFAOYSA-N isoamylol Chemical compound CC(C)CCO PHTQWCKDNZKARW-UHFFFAOYSA-N 0.000 description 31
- 239000008384 inner phase Substances 0.000 description 20
- 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 description 18
- 239000000661 sodium alginate Substances 0.000 description 18
- 235000010413 sodium alginate Nutrition 0.000 description 18
- 229940005550 sodium alginate Drugs 0.000 description 18
- 239000002245 particle Substances 0.000 description 17
- ZXEKIIBDNHEJCQ-UHFFFAOYSA-N isobutanol Chemical compound CC(C)CO ZXEKIIBDNHEJCQ-UHFFFAOYSA-N 0.000 description 16
- AMQJEAYHLZJPGS-UHFFFAOYSA-N N-Pentanol Chemical compound CCCCCO AMQJEAYHLZJPGS-UHFFFAOYSA-N 0.000 description 14
- ZSIAUFGUXNUGDI-UHFFFAOYSA-N hexan-1-ol Chemical compound CCCCCCO ZSIAUFGUXNUGDI-UHFFFAOYSA-N 0.000 description 14
- 238000007711 solidification Methods 0.000 description 14
- 230000008023 solidification Effects 0.000 description 14
- 238000001179 sorption measurement Methods 0.000 description 13
- 239000011259 mixed solution Substances 0.000 description 12
- NOOLISFMXDJSKH-UTLUCORTSA-N (+)-Neomenthol Chemical compound CC(C)[C@@H]1CC[C@@H](C)C[C@@H]1O NOOLISFMXDJSKH-UTLUCORTSA-N 0.000 description 8
- BBMCTIGTTCKYKF-UHFFFAOYSA-N 1-heptanol Chemical compound CCCCCCCO BBMCTIGTTCKYKF-UHFFFAOYSA-N 0.000 description 8
- NOOLISFMXDJSKH-UHFFFAOYSA-N DL-menthol Natural products CC(C)C1CCC(C)CC1O NOOLISFMXDJSKH-UHFFFAOYSA-N 0.000 description 8
- GHASVSINZRGABV-UHFFFAOYSA-N Fluorouracil Chemical compound FC1=CNC(=O)NC1=O GHASVSINZRGABV-UHFFFAOYSA-N 0.000 description 8
- 239000007864 aqueous solution Substances 0.000 description 8
- 229960002949 fluorouracil Drugs 0.000 description 8
- 229940041616 menthol Drugs 0.000 description 8
- 239000000463 material Substances 0.000 description 7
- CETWDUZRCINIHU-UHFFFAOYSA-N 2-heptanol Chemical compound CCCCCC(C)O CETWDUZRCINIHU-UHFFFAOYSA-N 0.000 description 6
- RZKSECIXORKHQS-UHFFFAOYSA-N Heptan-3-ol Chemical compound CCCCC(O)CC RZKSECIXORKHQS-UHFFFAOYSA-N 0.000 description 6
- AQIXEPGDORPWBJ-UHFFFAOYSA-N pentan-3-ol Chemical compound CCC(O)CC AQIXEPGDORPWBJ-UHFFFAOYSA-N 0.000 description 6
- 239000004094 surface-active agent Substances 0.000 description 6
- PQLVXDKIJBQVDF-UHFFFAOYSA-N acetic acid;hydrate Chemical compound O.CC(O)=O PQLVXDKIJBQVDF-UHFFFAOYSA-N 0.000 description 5
- DKAGJZJALZXOOV-UHFFFAOYSA-N hydrate;hydrochloride Chemical compound O.Cl DKAGJZJALZXOOV-UHFFFAOYSA-N 0.000 description 5
- 230000008569 process Effects 0.000 description 5
- 238000001035 drying Methods 0.000 description 4
- 150000002500 ions Chemical class 0.000 description 4
- 229920006395 saturated elastomer Polymers 0.000 description 4
- 230000004913 activation Effects 0.000 description 3
- 239000002585 base Substances 0.000 description 3
- 238000006243 chemical reaction Methods 0.000 description 3
- 238000004945 emulsification Methods 0.000 description 3
- 238000005516 engineering process Methods 0.000 description 3
- 238000001000 micrograph Methods 0.000 description 3
- 239000000377 silicon dioxide Substances 0.000 description 3
- 238000003756 stirring Methods 0.000 description 3
- 238000000859 sublimation Methods 0.000 description 3
- 230000008022 sublimation Effects 0.000 description 3
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
- NWGKJDSIEKMTRX-AAZCQSIUSA-N Sorbitan monooleate Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OC[C@@H](O)[C@H]1OC[C@H](O)[C@H]1O NWGKJDSIEKMTRX-AAZCQSIUSA-N 0.000 description 2
- 150000007513 acids Chemical class 0.000 description 2
- 239000012752 auxiliary agent Substances 0.000 description 2
- 230000008859 change Effects 0.000 description 2
- 230000001186 cumulative effect Effects 0.000 description 2
- 238000010586 diagram Methods 0.000 description 2
- PCHJSUWPFVWCPO-UHFFFAOYSA-N gold Chemical compound [Au] PCHJSUWPFVWCPO-UHFFFAOYSA-N 0.000 description 2
- 239000010931 gold Substances 0.000 description 2
- 229910052737 gold Inorganic materials 0.000 description 2
- 238000011068 loading method Methods 0.000 description 2
- 239000011148 porous material Substances 0.000 description 2
- 238000005507 spraying Methods 0.000 description 2
- 238000000870 ultraviolet spectroscopy Methods 0.000 description 2
- 229920000936 Agarose Polymers 0.000 description 1
- 229920002101 Chitin Polymers 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- SXRSQZLOMIGNAQ-UHFFFAOYSA-N Glutaraldehyde Chemical compound O=CCCCC=O SXRSQZLOMIGNAQ-UHFFFAOYSA-N 0.000 description 1
- 229910021578 Iron(III) chloride Inorganic materials 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 239000003929 acidic solution Substances 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 239000004964 aerogel Substances 0.000 description 1
- 125000003277 amino group Chemical group 0.000 description 1
- 229920000469 amphiphilic block copolymer Polymers 0.000 description 1
- 230000000844 anti-bacterial effect Effects 0.000 description 1
- 239000011260 aqueous acid Substances 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 230000000740 bleeding effect Effects 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 229910052927 chalcanthite Inorganic materials 0.000 description 1
- 239000002131 composite material Substances 0.000 description 1
- 238000013270 controlled release Methods 0.000 description 1
- 230000001276 controlling effect Effects 0.000 description 1
- 238000004132 cross linking Methods 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 1
- 238000004821 distillation Methods 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 238000005538 encapsulation Methods 0.000 description 1
- 238000001125 extrusion Methods 0.000 description 1
- 239000000835 fiber Substances 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 239000000796 flavoring agent Substances 0.000 description 1
- 235000019634 flavors Nutrition 0.000 description 1
- HQVFCQRVQFYGRJ-UHFFFAOYSA-N formic acid;hydrate Chemical compound O.OC=O HQVFCQRVQFYGRJ-UHFFFAOYSA-N 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 229910001385 heavy metal Inorganic materials 0.000 description 1
- 239000000017 hydrogel Substances 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 229920002521 macromolecule Polymers 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 239000003094 microcapsule Substances 0.000 description 1
- 239000002480 mineral oil Substances 0.000 description 1
- 235000010446 mineral oil Nutrition 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
- 239000002114 nanocomposite Substances 0.000 description 1
- 239000002086 nanomaterial Substances 0.000 description 1
- 229920005615 natural polymer Polymers 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 239000008055 phosphate buffer solution Substances 0.000 description 1
- 239000002953 phosphate buffered saline Substances 0.000 description 1
- 229920001282 polysaccharide Polymers 0.000 description 1
- 239000005017 polysaccharide Substances 0.000 description 1
- 150000004804 polysaccharides Chemical class 0.000 description 1
- 230000001737 promoting effect Effects 0.000 description 1
- 230000005588 protonation Effects 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 159000000000 sodium salts Chemical class 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 238000002336 sorption--desorption measurement Methods 0.000 description 1
- 230000006641 stabilisation Effects 0.000 description 1
- 238000011105 stabilization Methods 0.000 description 1
- 230000000087 stabilizing effect Effects 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 230000002522 swelling effect Effects 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- UNXRWKVEANCORM-UHFFFAOYSA-N triphosphoric acid Chemical compound OP(O)(=O)OP(O)(=O)OP(O)(O)=O UNXRWKVEANCORM-UHFFFAOYSA-N 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 230000029663 wound healing Effects 0.000 description 1
Images
Classifications
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J13/00—Colloid chemistry, e.g. the production of colloidal materials or their solutions, not otherwise provided for; Making microcapsules or microballoons
- B01J13/02—Making microcapsules or microballoons
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/513—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim having oxo groups directly attached to the heterocyclic ring, e.g. cytosine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
- A61K47/36—Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
- A61K9/1605—Excipients; Inactive ingredients
- A61K9/1629—Organic macromolecular compounds
- A61K9/1652—Polysaccharides, e.g. alginate, cellulose derivatives; Cyclodextrin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J20/00—Solid sorbent compositions or filter aid compositions; Sorbents for chromatography; Processes for preparing, regenerating or reactivating thereof
- B01J20/02—Solid sorbent compositions or filter aid compositions; Sorbents for chromatography; Processes for preparing, regenerating or reactivating thereof comprising inorganic material
- B01J20/06—Solid sorbent compositions or filter aid compositions; Sorbents for chromatography; Processes for preparing, regenerating or reactivating thereof comprising inorganic material comprising oxides or hydroxides of metals not provided for in group B01J20/04
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J20/00—Solid sorbent compositions or filter aid compositions; Sorbents for chromatography; Processes for preparing, regenerating or reactivating thereof
- B01J20/02—Solid sorbent compositions or filter aid compositions; Sorbents for chromatography; Processes for preparing, regenerating or reactivating thereof comprising inorganic material
- B01J20/10—Solid sorbent compositions or filter aid compositions; Sorbents for chromatography; Processes for preparing, regenerating or reactivating thereof comprising inorganic material comprising silica or silicate
- B01J20/103—Solid sorbent compositions or filter aid compositions; Sorbents for chromatography; Processes for preparing, regenerating or reactivating thereof comprising inorganic material comprising silica or silicate comprising silica
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J20/00—Solid sorbent compositions or filter aid compositions; Sorbents for chromatography; Processes for preparing, regenerating or reactivating thereof
- B01J20/02—Solid sorbent compositions or filter aid compositions; Sorbents for chromatography; Processes for preparing, regenerating or reactivating thereof comprising inorganic material
- B01J20/20—Solid sorbent compositions or filter aid compositions; Sorbents for chromatography; Processes for preparing, regenerating or reactivating thereof comprising inorganic material comprising free carbon; comprising carbon obtained by carbonising processes
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J20/00—Solid sorbent compositions or filter aid compositions; Sorbents for chromatography; Processes for preparing, regenerating or reactivating thereof
- B01J20/22—Solid sorbent compositions or filter aid compositions; Sorbents for chromatography; Processes for preparing, regenerating or reactivating thereof comprising organic material
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J20/00—Solid sorbent compositions or filter aid compositions; Sorbents for chromatography; Processes for preparing, regenerating or reactivating thereof
- B01J20/22—Solid sorbent compositions or filter aid compositions; Sorbents for chromatography; Processes for preparing, regenerating or reactivating thereof comprising organic material
- B01J20/24—Naturally occurring macromolecular compounds, e.g. humic acids or their derivatives
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J20/00—Solid sorbent compositions or filter aid compositions; Sorbents for chromatography; Processes for preparing, regenerating or reactivating thereof
- B01J20/28—Solid sorbent compositions or filter aid compositions; Sorbents for chromatography; Processes for preparing, regenerating or reactivating thereof characterised by their form or physical properties
- B01J20/28014—Solid sorbent compositions or filter aid compositions; Sorbents for chromatography; Processes for preparing, regenerating or reactivating thereof characterised by their form or physical properties characterised by their form
- B01J20/28016—Particle form
- B01J20/28021—Hollow particles, e.g. hollow spheres, microspheres or cenospheres
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J2220/00—Aspects relating to sorbent materials
- B01J2220/40—Aspects relating to the composition of sorbent or filter aid materials
- B01J2220/48—Sorbents characterised by the starting material used for their preparation
- B01J2220/4806—Sorbents characterised by the starting material used for their preparation the starting material being of inorganic character
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J2220/00—Aspects relating to sorbent materials
- B01J2220/40—Aspects relating to the composition of sorbent or filter aid materials
- B01J2220/48—Sorbents characterised by the starting material used for their preparation
- B01J2220/4812—Sorbents characterised by the starting material used for their preparation the starting material being of organic character
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J2220/00—Aspects relating to sorbent materials
- B01J2220/40—Aspects relating to the composition of sorbent or filter aid materials
- B01J2220/48—Sorbents characterised by the starting material used for their preparation
- B01J2220/4812—Sorbents characterised by the starting material used for their preparation the starting material being of organic character
- B01J2220/4825—Polysaccharides or cellulose materials, e.g. starch, chitin, sawdust, wood, straw, cotton
Abstract
The invention discloses a microfluidic preparation method of marine polymer microspheres and application thereof, comprising the following steps: (1) the method comprises the following steps of taking a marine high-molecular solution as an internal phase liquid and an organic solvent as an external phase liquid, simultaneously introducing the internal phase liquid and the external phase liquid into a micro-fluidic device, and forming independent micro-droplets at an outlet of a capillary tube by the internal phase liquid under the strong shearing action of the external phase liquid; (2) and the independent micro-droplets enter a receiving liquid under the carrying of an external phase liquid, are gradually solidified, separated out and condensed, and are cured to obtain the stable marine polymer microspheres. The invention adopts a micro-fluidic method without emulsifier and organic cross-linking agent to prepare the marine polymer microspheres, thereby avoiding the toxicity and harmfulness of the emulsifier and the organic cross-linking agent, and also avoiding the problems of complicated elution of the emulsifier and the unreacted organic cross-linking agent, wastewater discharge and residue and the like.
Description
Technical Field
The invention belongs to the technical field of preparation of marine polymer microspheres, and particularly relates to a microfluidic preparation method and application of marine polymer microspheres.
Background
As a natural rich renewable natural polymer resource, chitosan, a deacetylated product of marine polymers such as chitin, is a natural unique basic polysaccharide, has good biocompatibility, biodegradability and antibacterial performance, and has the functions of stopping bleeding and promoting wound healing.
A large number of randomly arranged amino groups exist in a chitosan molecular chain, and can be dissolved by protonation in an acidic medium, so that new materials such as chitosan fiber, chitosan films, chitosan hydrogel, chitosan aerogel, chitosan microspheres and the like can be prepared by using a chitosan solution. The chitosan microsphere material has the advantages of high specific surface area, easiness in treatment and the like, and has wide application prospects in the fields of separation and adsorption, biomedical materials, controlled release carriers and the like.
Alginic acid and sodium salt thereof (sodium alginate) are another marine polymer with abundant resources, have excellent biocompatibility and are widely applied to preparation of biomedical materials. The preparation method of the chitosan microspheres or the alginic acid microspheres is different, such as emulsion method, reversed phase emulsification method, SPG membrane emulsification method and the like which adopt various surfactants (emulsifiers). However, since the surfactant has amphiphilicity, the marine polymer microspheres prepared by the above method have problems of difficulty in eluting the surfactant, non-uniform microsphere size, and the like.
The microfluidic technology is a technology for operating micro-volume liquid developed on a microfluidic chip, has the advantages of small droplet volume, easy and accurate control, stable reaction conditions and the like, and is applied to a plurality of fields of physics, chemistry and biology, such as cell research, material preparation, chemical reaction and the like. In particular, the micro-fluidic technology is adopted to prepare micro-nano materials, and the size and microstructure of the materials are accurately controlled, so that the micro-fluidic material is one of important leading-edge fields in the field. The formation of the liquid drops mainly comprises two modes of T-shaped channels and flow focusing. Extruding the internal phase (disperse phase) polymer solution from a capillary tube of a certain diameter under a certain pressure, wherein the extruded polymer liquid is spherical due to surface tension and an extrusion swelling effect; under the high shearing action of the external phase (continuous phase) flowing at high speed, the spherical polymer liquid at the tail end of the capillary is cut off, so that independent micro-droplets are formed; the independent and stable micro-droplets can only present a regular spherical shape under the action of surface tension. For example, He et al (Carbohydr. Polymer., 2020, 236: 116094) added surfactant Span 80(Span 80) to the mineral oil external phase at a concentration of 0.84g/L, thereby stabilizing the micro-droplets of the cleaved chitosan solution; dripping the obtained micro-droplets of the spherical chitosan solution into an isopropanol aqueous solution receiving solution containing cross-linking agents of tripolyphosphoric acid and glutaraldehyde, and carrying out cross-linking reaction and solidification on the chitosan to obtain the chitosan microspheres. Xu et al (adv. healthcare mater.2012, 1, 106-. It can be seen that the stabilization of the individual polymer solution microdroplets in the high-speed flowing external phase, as well as the stable presence and uniform solidification of the microdroplets in the receiving liquid, are key to obtaining the final polymer microspheres and controlling their size and microstructure. For this purpose, chitosan microspheres (e.g. CN111748109A, CN111085148A, CN108855233A, CN106267164A, CN106040120A and CN105771929A) can be prepared by microfluidics by adding a suitable surfactant to the external phase and/or the receiving liquid and adding a suitable organic cross-linking agent to the receiving liquid. Chau et al (Biomacromolecules, 2014, 15: 2419-2425) add a specific surfactant, namely an amphiphilic block copolymer, into the external phase, add a crosslinking agent, namely phenolic hydroxyl gelatin, into the internal phase, and keep the temperature of a microfluidic system higher and a receiving solution at a lower temperature to prepare the alginic acid/agarose composite microspheres.
However, in the prior art, the auxiliary agents such as the emulsifier, the organic cross-linking agent and the like are often toxic and harmful, or are complex to prepare, or are too expensive. Under the condition of adopting the auxiliary agents, the chitosan microspheres or the alginic acid microspheres are prepared by a microfluidic method, and the problems of elution of an emulsifier and an unreacted cross-linking agent, discharge of waste water and residue generated by the elution, and the like are also involved, so that the process steps are more complicated, and the cost is increased. Therefore, the chitosan microspheres and the alginic acid microspheres prepared by developing a micro-flow control method without emulsifier and organic cross-linking agent have important scientific significance and practical value.
Disclosure of Invention
The invention aims to overcome the defects of the prior art and provides a microfluidic preparation method of marine polymer microspheres.
The invention also aims to provide the application of the marine polymer microspheres prepared by the microfluidic preparation method.
The technical scheme of the invention is as follows:
a micro-fluidic preparation method of marine polymer microspheres comprises the following steps:
(1) the method comprises the following steps of taking a marine high-molecular solution as an internal phase liquid and an organic solvent as an external phase liquid, simultaneously introducing the internal phase liquid and the external phase liquid into a micro-fluidic device, and forming independent micro-droplets at an outlet of a capillary tube by the internal phase liquid under the strong shearing action of the external phase liquid;
(2) the independent micro-droplets enter a receiving liquid under the carrying of an external phase liquid, are gradually solidified, separated out and condensed, and are cured to obtain the stable marine polymer microspheres;
the marine polymer solution is a chitosan solution or a alginic acid solution, wherein the solvent of the chitosan solution is an acid water solution with the pH value of less than 5, and the solvent of the alginic acid solution is water;
the organic solvent is at least one of alcohol having 4 to 7 carbon atoms, ethyl acetate and dimethyl carbonate;
when the marine polymer solution is chitosan solution, the receiving liquid consists of the organic solvent and alkali dissolved in the organic solvent.
When the marine polymer solution is alginic acid solution, the receiving solution is composed of the organic solvent and polyvalent metal salt dissolved therein.
In a preferred embodiment of the present invention, the alcohol is at least one of isobutanol, 1-pentanol, isopentanol, 3-pentanol, 1-hexanol, 1-heptanol, 2-heptanol, and 3-heptanol.
In a preferred embodiment of the present invention, the concentration of the marine macromolecule solution is 0.3-5 wt%.
Preferably, the marine polymer solution further contains water-dispersible nanoparticles, and the water-dispersible nanoparticles are at least one of hydrophilic graphene, nano silicon dioxide and nano ferroferric oxide.
In a preferred embodiment of the present invention, the solute of the aqueous acid solution is at least one of hydrochloric acid, sulfuric acid, nitric acid, acetic acid, and formic acid.
In a preferred embodiment of the invention, the base is at least one of sodium hydroxide, potassium hydroxide and lithium hydroxide, and its concentration in the receiving liquid is 0.1-5 wt%.
In a preferred embodiment of the present invention, the polyvalent metal salt is at least one of a divalent calcium inorganic salt, a trivalent iron inorganic salt, a divalent iron inorganic salt and a trivalent aluminum inorganic salt, and has a concentration of 0.1 to 5 wt% in the receiving liquid.
Further preferably, the polyvalent metal is at least one of calcium chloride, calcium nitrate, calcium sulfate, ferric chloride, ferric dichloride, ferric sulfate, ferrous sulfate, ferric nitrate, ferrous nitrate, aluminum trichloride and aluminum nitrate.
In a preferred embodiment of the present invention, the diameter of the capillary outlet is 50 to 1000. mu.m, the flow rate of the internal phase liquid is 1 to 20mL/h, and the ratio of the flow rate of the internal phase liquid to the flow rate of the external phase liquid is 1: 5 to 100.
The ocean polymer microsphere prepared by the microfluidic preparation method is applied as an adsorbent.
The marine polymer microsphere prepared by the microfluidic preparation method is applied as a drug sustained release carrier.
The invention has the beneficial effects that:
1. the invention adopts a micro-fluidic method without emulsifier and organic cross-linking agent to prepare the marine polymer microsphere, thereby avoiding the toxicity and harmfulness of the emulsifier and the organic cross-linking agent, and also avoiding the problems of complicated elution of the emulsifier and the unreacted organic cross-linking agent, the discharge of waste water and residue generated by the elution, and the like.
2. The invention has simple and convenient process and easy industrialized production, and the used organic solvent can be completely recovered by mature distillation and rectification processes, thereby realizing a green process with zero emission and lower cost.
3. The marine polymer microsphere prepared by the invention is in a regular spherical shape in water or ethanol, has a smooth surface, uniform and controllable particle size (300-.
4. The prepared marine polymer microsphere can be directly applied in a wet state, can also be used after being dried, and can be used as an adsorbent and a drug sustained-release carrier.
Drawings
FIG. 1 is a microphotograph of chitosan microspheres prepared in example 2 of the present invention.
FIG. 2 is a graph showing the variation of the particle size of chitosan microspheres according to the outlet diameter of capillary tube, which is prepared in example 5 of the present invention.
FIG. 3 is a microphotograph of the chitosan microsphere prepared in example 7 of the present invention (the left image uses ethyl acetate as an external phase and NaOH solution thereof as a receiving solution, and the right image uses dimethyl carbonate as an external phase and NaOH solution thereof as a receiving solution).
FIG. 4 is a microphotograph of chitosan microspheres prepared in example 8 of the present invention.
FIG. 5 is a photomicrograph of chitosan microspheres prepared from different bases according to example 9 of the present invention (NaOH on the left, KOH in the middle, LiOH on the right).
FIG. 6 is a photomicrograph of chitosan microspheres prepared from different acids according to example 10 of the present invention (hydrochloric acid in the upper row, acetic acid in the lower row, wet in the left, and dried in the right).
Fig. 7 is a scanning electron microscope photograph of the chitosan microsphere prepared in example 11 of the present invention (the upper figure is the figure with graphene added, the middle figure is the figure with nano-silica added, and the lower figure is the figure with nano-ferroferric oxide added).
FIG. 8 is a digital photograph (top) and a scanning electron microscope photograph (bottom) of chitosan microspheres prepared in example 13 of the present invention.
FIG. 9 shows sodium alginate microspheres prepared in example 14 of the present invention, which uses 0.3% sodium alginate solution as the inner phase and 0.3% CaCl2The isoamyl alcohol is used as receiving liquid, the diameter of a capillary tube outlet with the diameter of 100 mu m is prepared into a microsphere wet state (the upper left figure), 2.0 percent sodium alginate solution is used as an inner phase, and 2 percent CaCl is used2The isoamyl alcohol is used as receiving liquid, the microspheres prepared by the capillary with the diameter of 700 mu m are in a wet state (upper right diagram) and a dry state (lower left diagram), 5.0 percent sodium alginate solution is used as an internal phase, and 5 percent CaCl is used2The isoamyl alcohol is the receiving liquid, and the microspheres prepared by the capillary with the diameter of 1000 μm are taken as a wet-state (lower right) digital photo.
Fig. 10 is a digital photograph of the sodium alginate microspheres prepared in example 15 of the present invention in wet (left) and dry (right) states, wherein organic solutions of calcium nitrate (upper), ferric nitrate (middle) and aluminum trichloride (lower) are used as receiving solutions.
FIG. 11 is the kinetics curves of isothermal adsorption of Cu ions at 30 ℃ for the prepared chitosan microspheres and alginic acid microspheres of example 16 of the present invention.
FIG. 12 is a cumulative integrated release profile of drug-loaded (5-fluorouracil) chitosan microspheres prepared in example 18 of the present invention in phosphate buffered saline at pH 7.4.
Detailed Description
The technical solution of the present invention will be further illustrated and described below with reference to the accompanying drawings by means of specific embodiments.
Example 1
Respectively dissolving chitosan in 0.5 vol% hydrochloric acid, sulfuric acid, nitric acid, acetic acid and formic acid water solution to prepare a solution with chitosan mass concentration of 1%. And taking the obtained chitosan solution as an internal phase, selecting isobutanol as an external phase, and taking the isobutanol solution of NaOH with the mass concentration of 1% as an acceptance solution. In a microfluidic system, the chitosan solution is respectively input into a capillary tube with the diameter of 100 mu m at an outlet through a pressure pump, the flow rate of the chitosan solution in the microfluidic system is regulated to be 1mL/h, and the chitosan solution is also input through the pressure pump at the same external phase and has the flow rate of 100 mL/h; the inner phase forms independent spherical micro-droplets under the shearing action of the outer phase, the outer phase is carried into a receiving liquid, and the spherical chitosan microspheres can be obtained after curing after about 10 min. The chitosan solution prepared from the aqueous solution of various acids can be used for preparing chitosan microspheres with uniform size, the grain diameter of wet chitosan microspheres prepared from hydrochloric acid, sulfuric acid and nitric acid is 300 mu m, the grain diameter of chitosan microspheres prepared from formic acid is 330 mu m, and the grain diameter of chitosan microspheres prepared from acetic acid is 390 mu m.
Example 2 (lower Chitosan concentration limit, lower alkali concentration limit)
Dissolving chitosan in 0.5 vol% acetic acid water solution to prepare solution with chitosan mass concentration of 0.3%. The obtained chitosan solution is used as an internal phase, isoamyl alcohol is selected as an external phase, and an isobutanol solution of 0.1% NaOH by mass concentration is used as an acceptance liquid. In a micro-fluidic system, the chitosan solution is input into a capillary tube with the diameter of 100 mu m at the outlet through a pressure pump, the flow rate of the chitosan solution in the micro-fluidic system is adjusted to be 4mL/h, and the chitosan solution is also input through the pressure pump at the same external phase and has the flow rate of 120 mL/h; the inner phase forms independent spherical micro-droplets under the shearing action of the outer phase, the outer phase is carried into a receiving liquid, and the chitosan microspheres can be obtained after solidification after about 30 min. The photograph of the obtained microspheres is shown in FIG. 1, and the particle size of the microspheres is statistically 833. + -. 76. mu.m.
Example 3 (lower limit of Mixed acid flow Rate)
Preparing 1 percent by volume of acetic acid aqueous solution and 0.5 percent by volume of nitric acid aqueous solution. And mixing the two solutions in equal volume to prepare a mixed acidic solution, and dissolving chitosan by using the mixed solution as a solvent to prepare a solution with the mass concentration of chitosan being 1.0%. The obtained chitosan solution is used as an internal phase, isoamyl alcohol is selected as an external phase, and an isoamyl alcohol solution of NaOH with the mass concentration of 1.0% is used as a receiving solution. In a microfluidic system, the chitosan solution is respectively input into a capillary tube with the diameter of 100 mu m at an outlet through a pressure pump, the flow rate of the chitosan solution in the microfluidic system is adjusted to be 4mL/h, and the chitosan solution is also input through the pressure pump at the same external phase and has the flow rate of 120 mL/h; the inner phase forms independent spherical micro-droplets under the shearing action of the outer phase, the micro-droplets are carried by the outer phase into a receiving liquid, and the chitosan microspheres can be obtained by curing after about 10min, wherein the particle size of the wet microspheres is 737 +/-30 mu m according to statistics.
Under the conditions, the chitosan microspheres can be prepared only by changing the flow rate of the external phase to be 20 mL/h. The particle size of the solidified chitosan microsphere is 1467 +/-109 mu m through statistics.
Example 4 (upper limit of inner diameter of capillary tube, upper limit of inner phase flow rate)
Dissolving chitosan in 1 vol% hydrochloric acid water solution to prepare a solution with the chitosan mass concentration of 0.5%. Taking the obtained chitosan solution as an internal phase, selecting 3-pentanol as an external phase, and taking a 3-pentanol solution of NaOH with the mass concentration of 1.0% as a receiving solution. In a microfluidic system, the chitosan solution is respectively input into a capillary tube with the diameter of 500 mu m at an outlet through a pressure pump, the flow rate of the chitosan solution in the microfluidic system is adjusted to be 20mL/h, and the chitosan solution is also input through the pressure pump at the same external phase and has the flow rate of 200 mL/h; the inner phase forms independent spherical micro-droplets under the shearing action of the outer phase, the micro-droplets are carried by the outer phase into a receiving liquid, the chitosan microspheres can be obtained after solidification after about 10min, and the particle size of the wet microspheres is 1420 +/-84 mu m according to statistics.
Example 5 influence of capillary inner diameter and Upper and lower limits of capillary inner diameter
Dissolving chitosan in 1 vol% hydrochloric acid water solution to prepare a solution with the mass concentration of chitosan being 1.0%. The obtained chitosan solution was used as an internal phase, 1-hexanol was used as an external phase, and a 1-hexanol solution of NaOH with a mass concentration of 1.0% was used as a receiving solution. In a microfluidic system, the chitosan solution is respectively input into capillaries with the diameters of 50, 100, 200, 300, 500 and 700 mu m at outlets through pressure pumps, the flow rate of the chitosan solution in the microfluidic system is adjusted to be 4mL/h, and the chitosan solution is also input through the pressure pumps when the chitosan solution is in the same external phase and the flow rate of the chitosan solution is 160 mL/h; the inner phase forms independent spherical micro-droplets under the shearing action of the outer phase, the outer phase is carried into a receiving liquid, and the chitosan microspheres can be obtained after solidification after about 10 min. The particle size of the wet and dried microspheres was counted and plotted against the capillary exit diameter, as shown in FIG. 2.
Example 6 (various heptanols)
Dissolving chitosan in 1 vol% hydrochloric acid water solution to prepare a solution with the mass concentration of chitosan being 1.0%. The obtained chitosan solution is taken as an inner phase, and 1-heptanol, 2-heptanol and 3-heptanol are respectively taken as outer phases, and NaOH solutions with the mass concentration of 1.0% prepared from the corresponding 1-heptanol, 2-heptanol and 3-heptanol are taken as receiving solutions. In a microfluidic system, the chitosan solution is input into a capillary tube with the diameter of 300 mu m at an outlet through a pressure pump, the flow rate of the chitosan solution in the microfluidic system is adjusted to be 4mL/h, and the chitosan solution is also input through the pressure pump at the same time of external phase and has the flow rate of 160 mL/h; the inner phase forms independent spherical micro-droplets under the shearing action of the outer phase, the outer phase is carried into a receiving liquid, and the chitosan microspheres can be obtained after solidification after about 60 min. The results show that different heptanols have little influence on the particle size of the obtained wet microspheres, and the influence is about 1000 mu m.
Example 7 (Ethyl acetate, dimethyl carbonate)
Dissolving chitosan in 1% hydrochloric acid aqueous solution by volume percent to prepare a solution with the mass concentration of chitosan of 1.0%. Taking the obtained chitosan solution as an internal phase, respectively selecting ethyl acetate and dimethyl carbonate as external phases, and taking NaOH solution with the mass concentration of 1.0% prepared from the corresponding ethyl acetate and dimethyl carbonate as receiving solution. In a microfluidic system, the chitosan solution is input into a capillary tube with the diameter of 300 mu m at an outlet through a pressure pump, the flow rate of the chitosan solution in the microfluidic system is adjusted to be 4mL/h, and the chitosan solution is also input through the pressure pump at the same time of external phase and has the flow rate of 160 mL/h; the inner phase forms independent spherical micro-droplets under the shearing action of the outer phase, the outer phase is carried into a receiving liquid, and the chitosan microspheres can be obtained after solidification after about 30 min. The photo of the obtained microspheres is shown in FIG. 3.
Example 8 (hybrid exterior)
Dissolving chitosan in 1 vol% hydrochloric acid water solution to prepare a solution with the mass concentration of chitosan being 1.0%. The obtained chitosan solution was used as an internal phase, and 1-pentanol and 1-hexanol were mixed in equal volume to obtain an external phase, and the above mixed solution of 1-pentanol and 1-hexanol was used as a receiving solution containing 1.0% by mass of NaOH. In a microfluidic system, the chitosan solution is respectively input into capillaries with the diameter of 300 mu m at the outlet through pressure pumps, the flow rate of the chitosan solution in the microfluidic system is adjusted to be 4mL/h, and the chitosan solution is also input through the pressure pumps when the chitosan solution is in the external phase and the flow rate of the chitosan solution is 160 mL/h; the inner phase forms independent spherical micro-droplets under the shearing action of the outer phase, the outer phase is carried into a receiving liquid, and the chitosan microspheres can be obtained after solidification after about 10 min. The photograph of the resulting microspheres is shown in FIG. 4, with particle sizes of 913. + -. 45 μm.
Example 9 (various bases)
Dissolving chitosan in 1 volume percent acetic acid water solution to prepare a solution with the mass concentration of chitosan being 1.0 percent. The obtained chitosan solution is used as an internal phase, isobutanol is used as an external phase, and isobutanol solutions of NaOH, KOH and LiOH with the mass concentration of 1.0% are respectively used as receiving solutions. In a micro-fluidic system, the chitosan solution is respectively input into capillaries with the diameter of 300 mu m at the outlets through pressure pumps, the flow rate of the chitosan solution in the micro-fluidic system is adjusted to be 4mL/h, and the chitosan solution is also input through the pressure pumps at the same external phase and has the flow rate of 160 mL/h; the inner phase forms independent spherical micro-droplets under the shearing action of the outer phase, the outer phase is carried into a receiving liquid, and the chitosan microspheres can be obtained after solidification after about 10 min. The photograph of the resulting microspheres is shown in FIG. 5.
Example 10 (solid, hollow)
Respectively dissolving chitosan in 1% hydrochloric acid and acetic acid aqueous solution by volume percent to prepare a solution with the chitosan mass concentration of 1.0%. The obtained chitosan solution was used as an internal phase, isoamyl alcohol was used as an external phase, and an isoamyl alcohol solution of NaOH with a mass concentration of 1.0% was used as a receiving solution. In a microfluidic system, the chitosan solution is respectively input into capillaries with the diameter of 300 mu m at the outlet through pressure pumps, the flow rate of the chitosan solution in the microfluidic system is adjusted to be 4mL/h, and the chitosan solution is also input through the pressure pumps at the same external phase and has the flow rate of 160 mL/h; the inner phase forms independent spherical micro-droplets under the shearing action of the outer phase, the outer phase is carried into a receiving liquid, and the chitosan microspheres can be obtained after solidification after about 10 min. The photographs of the microspheres obtained after thorough washing with ethanol, in wet state and after drying, are shown in FIG. 6. The wet particle size of the microspheres prepared from hydrochloric acid is 1014 +/-45 mu m, the particle size after drying is 331 +/-12 mu m, and the microspheres are in a regular spherical shape before and after drying; the microspheres prepared from acetic acid have a wet particle size of 786 +/-48 microns, a dried particle size of 373 +/-50 microns, a wet regular spherical shape and a flat and wrinkled shape after drying, so that the microspheres have a hollow microcapsule structure.
Example 11 (nanocomposite)
Dissolving chitosan in 1 volume percent acetic acid water solution, preparing solution with the mass concentration of chitosan being 1.0%, and then respectively adding water dispersible nano graphene, nano silicon dioxide and nano ferroferric oxide to prepare uniform mixed solution, wherein the content of nano particles is 1 percent of the total solute. The obtained chitosan solution was used as an internal phase, isoamyl alcohol was used as an external phase, and an isoamyl alcohol solution of NaOH with a mass concentration of 1.0% was used as a receiving solution. In a micro-fluidic system, the chitosan solution is respectively input into capillaries with the diameter of 300 mu m at the outlets through pressure pumps, the flow rate of the chitosan solution in the micro-fluidic system is adjusted to be 4mL/h, and the chitosan solution is also input through the pressure pumps at the same external phase and has the flow rate of 160 mL/h; the inner phase forms independent spherical micro-droplets under the shearing action of the outer phase, the outer phase is carried into a receiving liquid, and the chitosan microspheres can be obtained after solidification after about 20 min. The obtained microspheres were fully washed with ethanol, dried, treated with gold spraying, and photographed by a scanning electron microscope, and the results are shown in fig. 7. The result shows that the microspheres prepared by adding graphene are flat and collapse after being dried, and the surfaces of the microspheres are rough; after the microspheres prepared by adding the nano silicon dioxide are dried, the microspheres basically present regular spheres, compact inside and smooth surface; after the microspheres prepared by adding the nano ferroferric oxide are dried, the microspheres are in a spherical shape with a very rough surface.
Example 12 (Upper Chitosan concentration, Upper alkali concentration)
Dissolving chitosan in 1 vol% hydrochloric acid water solution to prepare 5.0 wt% chitosan solution. The chitosan solution thus obtained was used as an internal phase, 1-pentanol was used as an external phase, and the above-mentioned 1-pentanol containing 5.0% by mass of NaOH was used as an acceptor solution. In a microfluidic system, the chitosan solution is input into a capillary tube with the diameter of 500 mu m at an outlet through a pressure pump, the flow rate of the chitosan solution in the microfluidic system is adjusted to be 4mL/h, and the chitosan solution is also input through the pressure pump at the same time of external phase and has the flow rate of 200 mL/h; the inner phase forms independent spherical micro-droplets under the shearing action of the outer phase, and the micro-droplets are carried by the outer phase into a receiving liquid and can be solidified to obtain the chitosan microspheres after about 60 min. The wet particle size of the obtained microsphere is 1467 +/-85 microns.
Example 13 (bulk preparation)
Dissolving chitosan in 1 volume percent acetic acid water solution to prepare a solution with the chitosan mass concentration of 2.0 percent, and then adding self-made water-dispersible nano-silica to prepare a uniform mixed solution, wherein the content of the nano-silica is 10 percent of the total solute. The chitosan mixed solution was used as an internal phase, a mixed solution of 1-hexanol and ethyl acetate in equal volume was used as an external phase, and a mixed solution of 2.0% by mass NaOH in equal volume of 1-hexanol and ethyl acetate was used as a receiving solution. In a microfluidic system, the chitosan solution is input into a capillary tube with the diameter of 200 mu m at an outlet through a pressure pump, the flow rate of the chitosan solution in the microfluidic system is adjusted to be 4mL/h, and the chitosan solution is also input through the pressure pump at the same time of external phase and has the flow rate of 120 mL/h; the inner phase forms independent spherical micro-droplets under the shearing action of the outer phase, the outer phase is carried into a receiving liquid, and the chitosan microspheres can be obtained after solidification after about 10 min. Continuous preparation by this method, the daily yield of a single channel microfluidic system is about 3 g. About 10g of the microspheres obtained were washed with ethanol and dried, and photographed by a digital camera, and photographed by a scanning electron microscope after being treated with gold spraying, and the results are shown in fig. 8. The results show that the chitosan microspheres prepared by the method have regular apparent sphere and uniform size after being dried, the particle size is 307 +/-19 microns, and the microscopic surface is rough and has a large number of micropores. The specific surface area of the chitosan microsphere is 173.6m measured by nitrogen isothermal adsorption-desorption2The pore volume was 0.21mL/g and the pore diameter was 5.3 nm.
Example 14 (sodium alginate concentration, receiving solution concentration, outlet diameter range)
Dissolving sodium alginate in water to obtain solutions with mass concentration of 0.3%, 1%, 2% and 5%, and adding 2%Adding 10% of water-dispersible SiO to the sodium alginate solution2The nanoparticles are prepared into mixed solutions, which are used as the internal phase respectively. Adding CaCl2Dissolving in isoamyl alcohol to prepare solutions with mass concentration of 0.1%, 2% and 5%, and taking the solutions as receiving solutions respectively. In a micro-fluidic system, the sodium alginate solution is input into capillaries with the diameters of 100 microns, 200 microns, 700 microns and 1000 microns through a pressure pump, the flow rate of the capillaries in the micro-fluidic system is adjusted to be 2mL/h, and the external isoamylol is also input through the pressure pump at the same time and the flow rate is 120 mL/h; the inner phase forms independent spherical micro-droplets under the shearing action of the outer phase, the outer phase is carried by the outer phase and enters the various receiving liquids respectively, and the alginic acid microspheres can be obtained after solidification after about 10 min. FIG. 9 shows 0.3% CaCl with 0.3% sodium alginate solution as the internal phase2Isoamyl alcohol as receiving liquid, a microsphere wet state prepared by capillary tube outlet diameter of 100 mu m, 2.0 percent sodium alginate solution as internal phase and 2 percent CaCl2The isoamylol is used as receiving liquid, microspheres are prepared by the outlet diameter of a capillary tube of 700 mu m in wet state and dry state, 5.0 percent sodium alginate solution is used as an internal phase, and 5 percent CaCl is used2The isoamyl alcohol is used as a receiving liquid, and the wet-state photo of the microspheres prepared by the outlet diameter of a capillary with the diameter of 1000 mu m.
Example 15 (sodium alginate receiving liquid salt type)
Sodium alginate is dissolved in water to prepare a solution with the mass concentration of 3% as an internal phase. Respectively dissolving calcium nitrate, ferric nitrate, ferrous sulfate and aluminum trichloride in a mixed solution of isobutanol and 1-pentanol with the volume ratio of 1: 1 to prepare a solution with the mass concentration of 2%, and respectively using the solution as a receiving solution. In a micro-fluidic system, the sodium alginate solution is input into a capillary tube with the diameter of 700 mu m at an outlet through a pressure pump, the flow rate of the sodium alginate solution in the micro-fluidic system is adjusted to be 2mL/h, the external phase is a mixed solution of isobutanol and 1-pentanol with the volume ratio of 1: 1, and the mixed solution is also input through the pressure pump at the same time, and the flow rate is 120 mL/h; the inner phase forms independent spherical micro-droplets under the shearing action of the outer phase, the outer phase is carried by the outer phase and enters the various receiving liquids respectively, and the alginic acid microspheres can be obtained after solidification after about 10 min. FIG. 10 is a digital photograph of alginic acid microspheres prepared by the above process, using organic solutions of calcium nitrate, ferric nitrate, and aluminum trichloride as receiving solutions, respectively, in wet and dry states.
Example 16 (adsorption of heavy Metal ions)
Preparing CuSO4·5H2O aqueous solution and constant temperature in 30 ℃ water bath, 0.05g of the chitosan microspheres prepared in example 13 and the alginic acid microspheres prepared in example 14 (sodium alginate concentration 2%, 10% SiO added) were added under stirring at 150rpm2Nanoparticles, 2% CaCl2The receiving solution (2), outlet diameter 200 μm)0.05 g. After about 10min, CuSO can be observed4The blue color of the solution became significantly lighter. The concentration change of Cu ions in the adsorption process was measured by Pgeneral atomic absorption spectrometer, and the adsorption kinetics curve of the marine polymer microsphere to Cu ions was obtained, as shown in fig. 11. The saturated adsorption capacity of the chitosan microspheres to Cu is about 65mg/g, the saturated adsorption capacity of the alginic acid microspheres is about 78mg/g, the adsorption time for reaching the saturated adsorption is about 2 hours, but more than 80 percent of the saturated adsorption capacity can be reached in 30 min.
Example 17 (adsorption of menthol and Release)
An absolute ethanol solution of menthol was prepared at room temperature, 0.2g of the chitosan microsphere prepared in example 13 was added under stirring at 150rpm, and stirring was continued for 24 hours. The concentration of menthol before and after adsorption was measured at a wavelength of 205nm using an ultraviolet-visible spectrophotometer. The results show that the adsorption amount of the chitosan microspheres to menthol is about 127 mg/g.
Filtering and separating the menthol-adsorbed chitosan microspheres, and naturally airing at room temperature. Measuring the mass change of the chitosan microspheres adsorbing menthol by adopting a thermogravimetric analyzer according to a literature method (Nanjing railway academy of medicine 1997, 16 (2): 98-100) and adopting different heating rates, and obtaining the volatilization (sublimation) activation energy (E) and the volatilization rate constant (k) of volatile matters (menthol) of the chitosan microspheres, wherein the volatilization (sublimation) activation energy (E) and the volatilization rate constant (k) are respectively 153.9kJ/mol and 0.624 multiplied by 10-3min-1(ii) a Activation energy of volatilization (sublimation) with pure menthol (88.6kJ/mol) and volatilization rate constant (2.385X 10)-3min-1) Compared with the prior art, the chitosan microspheres have better effect on the flavor substance menthol after adsorbing the mentholThe slow release function of (1).
Example 18 (drug loading and Release)
Dissolving chitosan in 1 volume percent acetic acid water solution, adding 5-fluorouracil, and preparing a mixed solution with the mass concentration of the chitosan being 1.0% and the mass concentration of the 5-fluorouracil being 0.05%. The obtained chitosan solution containing 5-fluorouracil is used as an internal phase, isoamyl alcohol is used as an external phase, and an isoamyl alcohol solution of NaOH with the mass concentration of 1.0% is used as a receiving solution. In a microfluidic system, the chitosan solution is respectively input into capillaries with the diameter of 100 mu m at the outlet through pressure pumps, the flow rate of the chitosan solution in the microfluidic system is adjusted to be 2mL/h, and the chitosan solution is also input through the pressure pumps when the chitosan solution is in the external phase and the flow rate of the chitosan solution is 160 mL/h; the inner phase forms independent spherical micro-droplets under the shearing action of the outer phase, the micro-droplets are carried by the outer phase into a receiving liquid, and the drug-loaded chitosan microspheres can be obtained after curing after about 10 min. The obtained microspheres are washed for 3 times by ethanol, the particle size of wet microspheres 563 +/-27 microns and the particle size of dried microspheres 178 +/-14 microns.
Adding the dried drug-loaded microspheres into 0.1% hydrochloric acid aqueous solution, dissolving by ultrasonic, and measuring the concentration of 5-fluorouracil at 266nm by an ultraviolet-visible spectrophotometer. The drug loading of the obtained 5-fluorouracil in the chitosan microsphere is 4.19%, and the encapsulation efficiency is 84.1%.
The dried drug-loaded microspheres are added into phosphate buffer solution with pH of 7.4, and in vitro release is carried out at the shaking speed of 100 r/min. At the set release time, 5 ml of the solution was passed through a UV-Vis spectrophotometer at 266nm to determine the concentration of 5-fluorouracil. Thus, a cumulative integrated release profile of 5-fluorouracil was obtained, as shown in FIG. 12. The result shows that the chitosan microsphere has good drug slow release function.
The above description is only a preferred embodiment of the present invention, and therefore should not be taken as limiting the scope of the invention, and all equivalent variations and modifications made within the scope of the present invention and the content of the description should be included in the scope of the present invention.
Claims (10)
1. A micro-fluidic preparation method of marine polymer microspheres is characterized by comprising the following steps: the method comprises the following steps:
(1) taking a marine high-molecular solution as an internal phase liquid and an organic solvent as an external phase liquid, simultaneously introducing the internal phase liquid and the external phase liquid into a microfluidic device, and forming independent micro-droplets by the internal phase liquid at a capillary outlet under the strong shearing action of the external phase liquid;
(2) the independent micro-droplets enter a receiving liquid under the carrying of an external phase liquid, are gradually solidified, separated out and condensed, and are cured to obtain the stable marine polymer microspheres;
the marine polymer solution is a chitosan solution or a alginic acid solution, wherein the solvent of the chitosan solution is an acid water solution with the pH value of less than 5, and the solvent of the alginic acid solution is water;
the organic solvent is at least one of alcohol having 4 to 7 carbon atoms, ethyl acetate and dimethyl carbonate;
when the marine polymer solution is chitosan solution, the receiving solution consists of the organic solvent and alkali dissolved in the organic solvent;
when the marine polymer solution is alginic acid solution, the receiving solution is composed of the organic solvent and polyvalent metal salt dissolved therein.
2. The microfluidic preparation method of claim 1, wherein: the concentration of the marine polymer solution is 0.3-5 wt%.
3. The microfluidic preparation method of claim 2, wherein: the marine polymer solution also contains water-dispersible nanoparticles, wherein the water-dispersible nanoparticles are at least one of hydrophilic graphene, nano silicon dioxide and nano ferroferric oxide.
4. The microfluidic preparation method of claim 1, wherein: the solute of the acid water solution is at least one of hydrochloric acid, sulfuric acid, nitric acid, acetic acid and formic acid.
5. The microfluidic preparation method of claim 1, wherein: the alkali is at least one of sodium hydroxide, potassium hydroxide and lithium hydroxide, and the concentration of the alkali in the receiving liquid is 0.1-5 wt%.
6. The microfluidic preparation method of claim 1, wherein: the multi-valence metal salt is at least one of divalent calcium inorganic salt, trivalent iron inorganic salt, divalent iron inorganic salt and trivalent aluminum inorganic salt, and the concentration of the multi-valence metal salt in the receiving liquid is 0.1-5 wt%.
7. The microfluidic preparation method of claim 6, wherein: the multi-valence state metal is at least one of calcium chloride, calcium nitrate, calcium sulfate, ferric trichloride, ferric dichloride, ferric sulfate, ferrous sulfate, ferric nitrate, ferrous nitrate, aluminum trichloride and aluminum nitrate.
8. The microfluidic preparation method according to any one of claims 1 to 7, wherein: the diameter of the capillary outlet is 50-1000 μm, the flow rate of the internal phase liquid is 1-20mL/h, and the ratio of the flow rate of the internal phase liquid to the flow rate of the external phase liquid is 1: 5-100.
9. Use of the marine polymeric microspheres prepared by the microfluidic preparation method according to any one of claims 1 to 8 as an adsorbent.
10. Use of the marine polymeric microspheres prepared by the microfluidic preparation method according to any one of claims 1 to 8 as a drug sustained release carrier.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202210046308.4A CN114471389A (en) | 2022-01-14 | 2022-01-14 | Micro-fluidic preparation method and application of marine polymer microspheres |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202210046308.4A CN114471389A (en) | 2022-01-14 | 2022-01-14 | Micro-fluidic preparation method and application of marine polymer microspheres |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN114471389A true CN114471389A (en) | 2022-05-13 |
Family
ID=81512897
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202210046308.4A Pending CN114471389A (en) | 2022-01-14 | 2022-01-14 | Micro-fluidic preparation method and application of marine polymer microspheres |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN114471389A (en) |
Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1607033A (en) * | 2003-10-15 | 2005-04-20 | 中国科学院过程工程研究所 | Chitose microsphere and microcapsule with uniform size and its preparation method |
| JP2008073581A (en) * | 2006-09-20 | 2008-04-03 | Univ Waseda | Microcapsule, microcapsule production device, and microcapsule production method |
| CN102134334A (en) * | 2010-12-29 | 2011-07-27 | 厦门大学 | Method for preparing magnetic chitosan microspheres |
| CN106040120A (en) * | 2016-05-24 | 2016-10-26 | 武汉理工大学 | Preparation method for SiO2 nanoparticle reinforced chitosan composite microcapsule |
| CN108514896A (en) * | 2018-03-23 | 2018-09-11 | 西南交通大学 | A kind of preparation method and device of micro-fluidic aqueous two-phase monodisperse calcium alginate microsphere |
| CN112138732A (en) * | 2020-09-27 | 2020-12-29 | 陕西科技大学 | Simple micro-fluidic device, magnetic alginate microspheres based on simple micro-fluidic device, and preparation method and application of magnetic alginate microspheres |
-
2022
- 2022-01-14 CN CN202210046308.4A patent/CN114471389A/en active Pending
Patent Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1607033A (en) * | 2003-10-15 | 2005-04-20 | 中国科学院过程工程研究所 | Chitose microsphere and microcapsule with uniform size and its preparation method |
| JP2008073581A (en) * | 2006-09-20 | 2008-04-03 | Univ Waseda | Microcapsule, microcapsule production device, and microcapsule production method |
| CN102134334A (en) * | 2010-12-29 | 2011-07-27 | 厦门大学 | Method for preparing magnetic chitosan microspheres |
| CN106040120A (en) * | 2016-05-24 | 2016-10-26 | 武汉理工大学 | Preparation method for SiO2 nanoparticle reinforced chitosan composite microcapsule |
| CN108514896A (en) * | 2018-03-23 | 2018-09-11 | 西南交通大学 | A kind of preparation method and device of micro-fluidic aqueous two-phase monodisperse calcium alginate microsphere |
| CN112138732A (en) * | 2020-09-27 | 2020-12-29 | 陕西科技大学 | Simple micro-fluidic device, magnetic alginate microspheres based on simple micro-fluidic device, and preparation method and application of magnetic alginate microspheres |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Niu et al. | Synthesis of nano/microstructures at fluid interfaces | |
| JP7270993B2 (en) | Structurally controllable ion-exchange nanofiber skeleton three-dimensional separation material and its manufacturing method | |
| JP4355655B2 (en) | Functional porous fiber | |
| You et al. | High flux low pressure thin film nanocomposite ultrafiltration membranes based on nanofibrous substrates | |
| CN101618869B (en) | Method for preparing small-size meso-porous hollow carbon sphere | |
| CN102794116B (en) | Mesoporous silicon dioxide sphere-polymer nano composite nano-filtration membrane and preparation method thereof | |
| Zhu et al. | Microfluidic synthesis of thiourea modified chitosan microsphere of high specific surface area for heavy metal wastewater treatment | |
| Yin et al. | Rationally designed hybrid molecularly imprinted polymer foam for highly efficient λ-cyhalothrin recognition and uptake via twice imprinting strategy | |
| CN111921387B (en) | Preparation method of polydopamine modified imidazolyl nanoparticle composite nanofiltration membrane | |
| CN110465208B (en) | Carbon material microbead/polymer composite membrane and preparation and application thereof | |
| CN105214502A (en) | A kind of Nano Silver/Graphene/polyvinyl alcohol mixing matrix membrane and preparation method thereof | |
| CN114028947A (en) | Reverse osmosis membrane modified by amino functionalized ZIFs nano material and preparation method thereof | |
| CN111632563A (en) | Hydrogel microsphere based on microfluidic technology and preparation method thereof | |
| CN112023899A (en) | Preparation method of hydrophilic flexible porous boron affinity imprinted hydrogel adsorbent | |
| CN101565529B (en) | Preparation method for inorganic/organic composite carrier provided with core-shell structure | |
| Deng et al. | Carbon quantum dots (CQDs) and polyethyleneimine (PEI) layer-by-layer (LBL) self-assembly PEK-C-based membranes with high forward osmosis performance | |
| Chen et al. | Bird's nest-inspired fabrication of ZIF-8 interlayer for organic solvent nanofiltration membranes | |
| CN114471389A (en) | Micro-fluidic preparation method and application of marine polymer microspheres | |
| Sen et al. | Novel polysulfone–spray-dried silica composite membrane for water purification: Preparation, characterization and performance evaluation | |
| Chen et al. | Double emulsion-templated microspheres with flow-through pores at micrometer scale | |
| CN109776873B (en) | Emulsion solvent volatilization method for preparing macroporous polymer microspheres | |
| Wang et al. | Shaping of metal-organic frameworks at the interface | |
| CN109880149B (en) | Preparation method of large-size polyurea hollow microspheres | |
| Xiong et al. | Honeycomb structured porous films prepared by the method of breath figure: history and development | |
| Sun et al. | Enhancing TFC membrane permeability by incorporating single-layer MSN into polyamide rejection layer |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination |