CN105796505A - Lincomycin carboxymethyl chitosan-gelatin composite microspheres and preparation method thereof - Google Patents
Lincomycin carboxymethyl chitosan-gelatin composite microspheres and preparation method thereof Download PDFInfo
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- CN105796505A CN105796505A CN201610158149.1A CN201610158149A CN105796505A CN 105796505 A CN105796505 A CN 105796505A CN 201610158149 A CN201610158149 A CN 201610158149A CN 105796505 A CN105796505 A CN 105796505A
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- carboxymethyl chitosan
- gelatin
- lincomycin
- microsphere
- preparation
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- 229960005287 lincomycin Drugs 0.000 title claims abstract description 53
- OJMMVQQUTAEWLP-UHFFFAOYSA-N Lincomycin Natural products CN1CC(CCC)CC1C(=O)NC(C(C)O)C1C(O)C(O)C(O)C(SC)O1 OJMMVQQUTAEWLP-UHFFFAOYSA-N 0.000 title claims abstract description 52
- 229920000159 gelatin Polymers 0.000 title claims abstract description 44
- 239000008273 gelatin Substances 0.000 title claims abstract description 37
- 239000004005 microsphere Substances 0.000 title claims abstract description 30
- 238000002360 preparation method Methods 0.000 title claims abstract description 19
- 239000002131 composite material Substances 0.000 title abstract 3
- 125000002057 carboxymethyl group Chemical group [H]OC(=O)C([H])([H])[*] 0.000 claims abstract description 34
- OJMMVQQUTAEWLP-KIDUDLJLSA-N lincomycin Chemical compound CN1C[C@H](CCC)C[C@H]1C(=O)N[C@H]([C@@H](C)O)[C@@H]1[C@H](O)[C@H](O)[C@@H](O)[C@@H](SC)O1 OJMMVQQUTAEWLP-KIDUDLJLSA-N 0.000 claims abstract description 30
- 238000000034 method Methods 0.000 claims abstract description 17
- 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 claims abstract description 15
- SXRSQZLOMIGNAQ-UHFFFAOYSA-N Glutaraldehyde Chemical compound O=CCCCC=O SXRSQZLOMIGNAQ-UHFFFAOYSA-N 0.000 claims abstract description 14
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims abstract description 12
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 claims abstract description 12
- 229940057995 liquid paraffin Drugs 0.000 claims abstract description 11
- 238000005406 washing Methods 0.000 claims abstract description 9
- 229920001661 Chitosan Polymers 0.000 claims abstract description 8
- 108010010803 Gelatin Proteins 0.000 claims abstract description 8
- 235000019322 gelatine Nutrition 0.000 claims abstract description 8
- 235000011852 gelatine desserts Nutrition 0.000 claims abstract description 8
- 238000003756 stirring Methods 0.000 claims abstract description 8
- 238000004132 cross linking Methods 0.000 claims abstract description 7
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 claims abstract description 6
- 239000003208 petroleum Substances 0.000 claims abstract description 6
- 238000001291 vacuum drying Methods 0.000 claims abstract description 6
- 239000001828 Gelatine Substances 0.000 claims description 7
- 238000001914 filtration Methods 0.000 claims description 7
- 239000000203 mixture Substances 0.000 claims description 6
- 239000003431 cross linking reagent Substances 0.000 claims description 4
- 238000007711 solidification Methods 0.000 claims description 4
- 230000008023 solidification Effects 0.000 claims description 4
- 239000000243 solution Substances 0.000 abstract description 8
- 238000004945 emulsification Methods 0.000 abstract description 3
- 230000015556 catabolic process Effects 0.000 abstract 1
- 238000006731 degradation reaction Methods 0.000 abstract 1
- 238000001035 drying Methods 0.000 abstract 1
- 239000011259 mixed solution Substances 0.000 abstract 1
- 231100000956 nontoxicity Toxicity 0.000 abstract 1
- 238000000967 suction filtration Methods 0.000 abstract 1
- 238000009210 therapy by ultrasound Methods 0.000 abstract 1
- 239000003814 drug Substances 0.000 description 8
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 6
- 230000000694 effects Effects 0.000 description 6
- POUMFISTNHIPTI-BOMBIWCESA-N hydron;(2s,4r)-n-[(1r,2r)-2-hydroxy-1-[(2r,3r,4s,5r,6r)-3,4,5-trihydroxy-6-methylsulfanyloxan-2-yl]propyl]-1-methyl-4-propylpyrrolidine-2-carboxamide;chloride Chemical compound Cl.CN1C[C@H](CCC)C[C@H]1C(=O)N[C@H]([C@@H](C)O)[C@@H]1[C@H](O)[C@H](O)[C@@H](O)[C@@H](SC)O1 POUMFISTNHIPTI-BOMBIWCESA-N 0.000 description 5
- 229960001595 lincomycin hydrochloride Drugs 0.000 description 5
- 239000000843 powder Substances 0.000 description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 4
- 239000002671 adjuvant Substances 0.000 description 3
- 230000000844 anti-bacterial effect Effects 0.000 description 3
- 229940079593 drug Drugs 0.000 description 3
- 230000001988 toxicity Effects 0.000 description 3
- 231100000419 toxicity Toxicity 0.000 description 3
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- 239000000654 additive Substances 0.000 description 2
- 238000006243 chemical reaction Methods 0.000 description 2
- 210000001072 colon Anatomy 0.000 description 2
- 230000000857 drug effect Effects 0.000 description 2
- 238000005516 engineering process Methods 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 238000002347 injection Methods 0.000 description 2
- 239000007924 injection Substances 0.000 description 2
- 238000011068 loading method Methods 0.000 description 2
- 239000007800 oxidant agent Substances 0.000 description 2
- 239000000546 pharmaceutical excipient Substances 0.000 description 2
- 239000006187 pill Substances 0.000 description 2
- 244000144977 poultry Species 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- 239000002994 raw material Substances 0.000 description 2
- 238000001179 sorption measurement Methods 0.000 description 2
- 238000013268 sustained release Methods 0.000 description 2
- 239000012730 sustained-release form Substances 0.000 description 2
- 241001662103 Cryptocarya corrugata Species 0.000 description 1
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 1
- 238000009825 accumulation Methods 0.000 description 1
- 239000003929 acidic solution Substances 0.000 description 1
- 239000012670 alkaline solution Substances 0.000 description 1
- 230000001580 bacterial effect Effects 0.000 description 1
- 238000006065 biodegradation reaction Methods 0.000 description 1
- 210000004027 cell Anatomy 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 230000007812 deficiency Effects 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- 239000002360 explosive Substances 0.000 description 1
- 239000012467 final product Substances 0.000 description 1
- 238000004108 freeze drying Methods 0.000 description 1
- BXWNKGSJHAJOGX-UHFFFAOYSA-N hexadecan-1-ol Chemical compound CCCCCCCCCCCCCCCCO BXWNKGSJHAJOGX-UHFFFAOYSA-N 0.000 description 1
- DKAGJZJALZXOOV-UHFFFAOYSA-N hydrate;hydrochloride Chemical compound O.Cl DKAGJZJALZXOOV-UHFFFAOYSA-N 0.000 description 1
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 description 1
- 244000144972 livestock Species 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 239000012982 microporous membrane Substances 0.000 description 1
- 210000004877 mucosa Anatomy 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 230000001590 oxidative effect Effects 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 239000008363 phosphate buffer Substances 0.000 description 1
- 239000002574 poison Substances 0.000 description 1
- 231100000614 poison Toxicity 0.000 description 1
- 238000004321 preservation Methods 0.000 description 1
- 108090000765 processed proteins & peptides Proteins 0.000 description 1
- 238000001243 protein synthesis Methods 0.000 description 1
- RYVMUASDIZQXAA-UHFFFAOYSA-N pyranoside Natural products O1C2(OCC(C)C(OC3C(C(O)C(O)C(CO)O3)O)C2)C(C)C(C2(CCC3C4(C)CC5O)C)C1CC2C3CC=C4CC5OC(C(C1O)O)OC(CO)C1OC(C1OC2C(C(OC3C(C(O)C(O)C(CO)O3)O)C(O)C(CO)O2)O)OC(CO)C(O)C1OC1OCC(O)C(O)C1O RYVMUASDIZQXAA-UHFFFAOYSA-N 0.000 description 1
- 239000002510 pyrogen Substances 0.000 description 1
- 210000002345 respiratory system Anatomy 0.000 description 1
- 210000003705 ribosome Anatomy 0.000 description 1
- 230000000638 stimulation Effects 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 229910052717 sulfur Inorganic materials 0.000 description 1
- 239000011593 sulfur Substances 0.000 description 1
- 238000013269 sustained drug release Methods 0.000 description 1
- RWRDLPDLKQPQOW-UHFFFAOYSA-N tetrahydropyrrole Substances C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 230000014616 translation Effects 0.000 description 1
- 239000008215 water for injection Substances 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/14—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
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7042—Compounds having saccharide radicals and heterocyclic rings
- A61K31/7052—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides
- A61K31/7056—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing five-membered rings with nitrogen as a ring hetero atom
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0002—Galenical forms characterised by the drug release technique; Application systems commanded by energy
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/14—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
- A61K9/1658—Proteins, e.g. albumin, gelatin
Abstract
The invention relates to lincomycin carboxymethyl chitosan-gelatin composite microspheres and a preparation method thereof. The microspheres are prepared through the method which includes the following steps that a normal saline solution, with the mass concentration of 1.5% to 3.0%, of carboxymethyl chitosan-gelatin is prepared, ultrasonic treatment is conducted for 7-10 min, full stirring is conducted, then lincomycin is added, the evenly-mixed solution is added to liquid paraffin containing Span80, and stirring is conducted for 1 h at the rotating speed of 500 r/min; glutaraldehyde is added for cross-linking and curing for 2 h, and suction filtration is conducted through a sand core funnel; petroleum ether and isopropanol are used for alternate washing, washing is conducted four times in total, drying is conducted for 8 h in a 45-DEG C vacuum drying box, and then the lincomycin carboxymethyl chitosan-gelatin composite microspheres are obtained. The lincomycin microspheres are mainly prepared from carboxymethyl chitosan and gelatin which are good in biological compatibility, no toxicity exists, biological degradation can be achieved, and good slow release performance is achieved after emulsification and cross-linking.
Description
Technical field
The present invention relates to field of pharmaceutical preparations, in particular it relates to a kind of lincomycin carboxymethyl chitosan-gelatin-compounded
Microsphere and preparation method thereof.
Background technology
Lincomycin (Lincomycin Hydrochloride), (also referred to as lincomycin hydrochloride), chemical entitled 6-(1-methyl-
Trans-4-propyl group-L-2-pyrrolidine formyl amino)-1-sulfur generation-6, the 8-dideoxy-D-erythro form pungent pyranoside of-α-D-gala
Hydrochloride monohydrate.Lincomycin is white crystalline powder；Have micro-smelly or special smelly；Bitter in the mouth.Lincomycin is in water or first
In alcohol readily soluble, the most molten.Lincomycin acts on sensitive organism ribosomal 50S subunit, stops the prolongation of peptide chain, from
And suppress the protein synthesis of bacterial cell.Lincomycin is typically antibacterial, but in higher concentrations, to extremely sensitive antibacterial also
There is bactericidal action.
CN102000036A patent application discloses the method for preparing colon targeted pill of lincomycin that a kind of poultry use, and uses woods
Can mycin as principal agent, use blank piller, wrap respectively medicine layer-lincomycin, 8% block layer-hexadecanol, 2%
Time lag layer-HPMC, 15%pH sensitive membrane-EudragitS100, the colon targeted pill of lincomycin that preparation poultry use.Should
Adjuvant hexadecanol used in product has stimulation to eyes, skin, mucosa and upper respiratory tract, has harm to environment, right
Water body can pollute, and powder body and air can form explosive mixture, meet naked light, Gao Re or and oxidising agent, have and draw
The danger of combust blast.
CN102000036A patent application discloses a kind of lincomycin hydrochloride freeze-dried powder injection for livestock injection and preparation side thereof
Method, this lincomycin hydrochloride lyophilized injectable powder comprises following components: lincomycin hydrochloride 3%～30%；Excipient 0.1%～
90%；Additives 0.1%～90%.Preparation method includes: in an aseptic environment, takes water for injection, and lucifuge adds hydrochloric acid woods
Can mycin and the excipient of recipe quantity, be sufficiently stirred for dissolve；Add additives regulation pH value between 4.0～6.5；Through super
Filter processes, and adds medicinal carbon stirring and adsorbing and removes pyrogen；Through 0.45 μm filtering with microporous membrane, constant volume；0.22 μm is micro-
Hole filter membrane end-filtration is degerming；Nitrogen charging subpackage, lyophilization, roll lid and seal preservation, to obtain final product.In the preparation method of this product
Adjuvant medicinal carbon used has certain combustibility, may catch fire in atmosphere and cause burning.Activated carbon can not be with
Oxidant is used in mixed way, and activated carbon ratio the most in an acidic solution has higher adsorption rate in alkaline solution, and pH value can be to suction
Attached matter state and dissolubility etc. present in the water produce impact, thus affect adsorption effect.
There is adjuvant side effect more in lincomycin medicament of the prior art bigger, it is impossible to biodegradation, it is impossible to effectively reduce medicine
The toxicity of thing, and the unconspicuous problem of sustained drug release effect.
Summary of the invention
The technical problem to be solved in the present invention is, overcomes the deficiencies in the prior art, with the carboxymethyl chitosan of good biocompatibility
Being that primary raw material produces lincomycin microsphere with gelatin, it does not has toxicity, and biodegradable, has preferably after emulsification and cross linked
Sustained release performance.It can reduce the medicine untoward reaction to body, reduces toxic and side effects, to extend drug effect, improves treatment
Effect, selects the optimised process preparing lincomycin carboxymethyl chitosan-gelatin-compounded microsphere by experiment.
The technical solution used in the present invention is:
The invention provides a kind of lincomycin carboxymethyl chitosan-gelatin-compounded microsphere, this microsphere is by the side comprised the steps
Method prepares: preparation mass concentration is the normal saline solution of the carboxymethyl chitosan-gelatin of 1.5%-3.0%, supersound process
7-10min also adds lincomycin after being sufficiently stirred for, and joins the solution after mix homogeneously containing 1.5%-2.5% (volume integral
Number) Span80 liquid paraffin in, with rotating speed 500r/min stir 1h；Add glutaraldehyde cross-linking solidification 2h, then through sand
Core funnel sucking filtration；With petroleum ether and isopropanol alternately washing, wash 4 times altogether, after being dried 8h in 45 DEG C of vacuum drying ovens,
Obtain lincomycin carboxymethyl chitosan-gelatine microsphere.Wherein the addition of carboxymethyl chitosan-gelatin is lincomycin quality
1-2 times；Cross-linking agent glutaraldehyde: carboxymethyl chitosan-gelatin=8-12mL:1g；Containing 1.5%-2.5% (volume fraction) Span80
Liquid paraffin: lincomycin=120mL:1g.
Preferably, described carboxymethyl chitosan is 1:1 with the mass ratio of gelatin.
Preferably, the mass concentration of described carboxymethyl chitosan-gelatin is 2%, and the addition of carboxymethyl chitosan-gelatin is woods
Can 1.5 times of mycin quality；Glutaraldehyde: carboxymethyl chitosan-gelatin=10mL:1g.Span80 volume fraction is 2.0%.
Present invention also offers the preparation method of a kind of lincomycin carboxymethyl chitosan-gelatin-compounded microsphere, the method include as
Lower step: preparation mass concentration is the normal saline solution of the carboxymethyl chitosan-gelatin of 1.5%-3.0%, supersound process
7-10min also adds lincomycin after being sufficiently stirred for, and joins the solution after mix homogeneously containing 1.5%-2.5% (volume integral
Number) Span80 liquid paraffin in, with rotating speed 500r/min stir 1h；Add glutaraldehyde cross-linking solidification 2h, then through sand
Core funnel sucking filtration；With petroleum ether and isopropanol alternately washing, wash 4 times altogether, after being dried 8h in 45 DEG C of vacuum drying ovens,
Obtain lincomycin carboxymethyl chitosan-gelatine microsphere.Wherein the addition of carboxymethyl chitosan-gelatin is lincomycin quality
1-2 times；Cross-linking agent glutaraldehyde: carboxymethyl chitosan-gelatin=8-12mL:1g；Containing 1.5%-2.5% (volume fraction) Span80
Liquid paraffin: lincomycin=120mL:1g.
In said method, it is preferable that described carboxymethyl chitosan is 1:1 with the mass ratio of gelatin.
In said method, it is preferable that the mass concentration of described carboxymethyl chitosan-gelatin is 2%, carboxymethyl chitosan-gelatin
Addition is lincomycin quality 1.5 times；Glutaraldehyde: carboxymethyl chitosan-gelatin=10mL:1g.Span80 volume fraction
It is 2.0%.
The present invention is had the advantages that
Producing lincomycin microsphere with carboxymethyl chitosan and the gelatin of good biocompatibility for primary raw material, it does not has toxicity, and
Biodegradable, there is after emulsification and cross linked preferable sustained release performance.It can reduce the medicine untoward reaction to body, reduces poison
Side effect, to extend drug effect, improves therapeutic effect.
Detailed description of the invention
Below in conjunction with specific embodiment, the invention will be further described, but does not limit protection scope of the present invention.
The preparation method of a kind of lincomycin carboxymethyl chitosan-gelatin-compounded microsphere, the method comprises the steps:
The normal saline solution of preparation carboxymethyl chitosan-gelatin, supersound process 8min also adds lincomycin after being sufficiently stirred for, will
Solution after mix homogeneously joins in the liquid paraffin containing Span80, stirs 1h with rotating speed 500r/min；Add glutaraldehyde
Crosslinking curing 2h, then through sand core funnel sucking filtration；With petroleum ether and isopropanol alternately washing, washing 4 times altogether, 45 DEG C of vacuum drying
After case is dried 8h, obtain lincomycin carboxymethyl chitosan-gelatine microsphere.Wherein said carboxymethyl chitosan and the quality of gelatin
Ratio is 1:1, containing the liquid paraffin of 1.5%-2.5% (volume fraction) Span80: lincomycin=120mL:1g.
Preparing microsphere according to parameter in above-mentioned table, by extracorporeal releasing experiment, lincomycin crude drug discharges in 50min
Complete, and lincomycin carboxymethyl chitosan-gelatine microsphere prepared by embodiment 1-9 is in pH6.8 phosphate buffer after 10h
Accumulation dissolution 100%.
By embodiment 1-9 it can be seen that the drug loading of lincomycin carboxymethyl chitosan-gelatine microsphere and envelop rate in embodiment 2
Reach 75%.Best results, prepares microsphere, drug loading and envelop rate in triplicate according to the process conditions of embodiment 2 and is respectively
74.97%, 75.91%, 75.58%, preparation technology repeatability is preferable.
Claims (6)
1. lincomycin carboxymethyl chitosan-gelatin-compounded microsphere, it is characterised in that: this microsphere is by comprising the steps
Method prepare: preparation mass concentration is the normal saline solution of carboxymethyl chitosan-gelatin of 1.5%-3.0%, ultrasonic
Add lincomycin after processing 7-10min and being sufficiently stirred for, the solution after mix homogeneously is joined containing 1.5%-2.5% (body
Fraction) Span80 liquid paraffin in, with rotating speed 500r/min stir 1h；Add glutaraldehyde cross-linking solidification 2h, then
Through sand core funnel sucking filtration；With petroleum ether and isopropanol alternately washing, washing 4 times altogether, 45 DEG C of vacuum drying ovens are dried 8h
After, obtain lincomycin carboxymethyl chitosan-gelatine microsphere, wherein the addition of carboxymethyl chitosan-gelatin is lincomycin matter
1-2 times of amount；Cross-linking agent glutaraldehyde: carboxymethyl chitosan-gelatin=8-12mL:1g；Containing 1.5%-2.5% (volume fraction)
The liquid paraffin of Span80: lincomycin=120mL:1g.
A kind of lincomycin carboxymethyl chitosan-gelatin-compounded microsphere, it is characterised in that: described
Carboxymethyl chitosan is 1:1 with the mass ratio of gelatin.
A kind of lincomycin carboxymethyl chitosan-gelatin-compounded microsphere the most according to claim 1 or claim 2, it is characterised in that: institute
The mass concentration of the carboxymethyl chitosan-gelatin stated is 2%, and the addition of carboxymethyl chitosan-gelatin is the 1.5 of lincomycin quality
Times；Glutaraldehyde: carboxymethyl chitosan-gelatin=10mL:1g.Span80 volume fraction is 2.0%.
4. the preparation method of lincomycin carboxymethyl chitosan-gelatin-compounded microsphere, it is characterised in that: the method include as
Lower step: preparation mass concentration is the normal saline solution of the carboxymethyl chitosan-gelatin of 1.5%-3.0%, supersound process
7-10min also adds lincomycin after being sufficiently stirred for, and joins the solution after mix homogeneously containing 1.5%-2.5% (volume integral
Number) Span80 liquid paraffin in, with rotating speed 500r/min stir 1h；Add glutaraldehyde cross-linking solidification 2h, then through sand
Core funnel sucking filtration；With petroleum ether and isopropanol alternately washing, wash 4 times altogether, after being dried 8h in 45 DEG C of vacuum drying ovens,
Obtain lincomycin carboxymethyl chitosan-gelatine microsphere.Wherein the addition of carboxymethyl chitosan-gelatin is lincomycin quality
1-2 times；Cross-linking agent glutaraldehyde: carboxymethyl chitosan-gelatin=8-12mL:1g；Containing 1.5%-2.5% (volume fraction) Span80
Liquid paraffin: lincomycin=120mL:1g.
The preparation method of a kind of lincomycin carboxymethyl chitosan-gelatin-compounded microsphere, its feature exists
In: described carboxymethyl chitosan is 1:1 with the mass ratio of gelatin.
6. according to the preparation method of lincomycin carboxymethyl chitosan-gelatin-compounded microsphere a kind of described in claim 4 or 5,
It is characterized in that: the mass concentration of described carboxymethyl chitosan-gelatin is 2%, the addition of carboxymethyl chitosan-gelatin is
1.5 times of lincomycin quality；Glutaraldehyde: carboxymethyl chitosan-gelatin=10mL:1g.Span80 volume fraction is 2.0%.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201610158149.1A CN105796505B (en) | 2016-03-18 | 2016-03-18 | A kind of lincomycin carboxymethyl chitosan-gelatin-compounded microballoon and preparation method thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201610158149.1A CN105796505B (en) | 2016-03-18 | 2016-03-18 | A kind of lincomycin carboxymethyl chitosan-gelatin-compounded microballoon and preparation method thereof |
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| Publication Number | Publication Date |
|---|---|
| CN105796505A true CN105796505A (en) | 2016-07-27 |
| CN105796505B CN105796505B (en) | 2018-10-16 |
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| CN201610158149.1A Expired - Fee Related CN105796505B (en) | 2016-03-18 | 2016-03-18 | A kind of lincomycin carboxymethyl chitosan-gelatin-compounded microballoon and preparation method thereof |
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|---|---|---|---|---|
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| CN105037456A (en) * | 2015-07-03 | 2015-11-11 | 武汉工程大学 | Method used for separating and purifying lincomycin with molecular imprinting polymers |
-
2016
- 2016-03-18 CN CN201610158149.1A patent/CN105796505B/en not_active Expired - Fee Related
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2004060447A2 (en) * | 2002-12-31 | 2004-07-22 | Ultra-Sonic Technologies, L.L.C. | Transdermal delivery using encapsulated agent activated by ultrasound and/or heat |
| CN104173295A (en) * | 2014-09-10 | 2014-12-03 | 四川兴科蓉药业有限责任公司 | Controlled-release lincomycin granules |
| CN105037456A (en) * | 2015-07-03 | 2015-11-11 | 武汉工程大学 | Method used for separating and purifying lincomycin with molecular imprinting polymers |
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| CN105796505B (en) | 2018-10-16 |
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