CN105796505B - A kind of lincomycin carboxymethyl chitosan-gelatin-compounded microballoon and preparation method thereof - Google Patents
A kind of lincomycin carboxymethyl chitosan-gelatin-compounded microballoon and preparation method thereof Download PDFInfo
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- CN105796505B CN105796505B CN201610158149.1A CN201610158149A CN105796505B CN 105796505 B CN105796505 B CN 105796505B CN 201610158149 A CN201610158149 A CN 201610158149A CN 105796505 B CN105796505 B CN 105796505B
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- gelatin
- carboxymethyl chitosan
- lincomycin
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- span80
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- Expired - Fee Related
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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
- 238000002360 preparation method Methods 0.000 title claims abstract description 13
- 229920000159 gelatin Polymers 0.000 claims abstract description 42
- 125000002057 carboxymethyl group Chemical group [H]OC(=O)C([H])([H])[*] 0.000 claims abstract description 34
- 239000008273 gelatin Substances 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 31
- 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
- 229920001661 Chitosan Polymers 0.000 claims abstract description 11
- 238000000034 method Methods 0.000 claims abstract description 10
- 239000004005 microsphere Substances 0.000 claims abstract description 9
- 239000001828 Gelatine Substances 0.000 claims abstract description 8
- 235000019322 gelatine Nutrition 0.000 claims abstract description 8
- 108010010803 Gelatin Proteins 0.000 claims abstract description 7
- 235000011852 gelatine desserts Nutrition 0.000 claims abstract description 7
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 claims abstract description 6
- 238000004132 cross linking Methods 0.000 claims abstract description 6
- 238000002156 mixing Methods 0.000 claims abstract description 6
- 239000003208 petroleum Substances 0.000 claims abstract description 6
- 238000007711 solidification Methods 0.000 claims abstract description 6
- 230000008023 solidification Effects 0.000 claims abstract description 6
- 238000001291 vacuum drying Methods 0.000 claims abstract description 6
- 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 description 10
- 239000000654 additive Substances 0.000 claims description 9
- 230000000996 additive effect Effects 0.000 claims description 7
- 239000003431 cross linking reagent Substances 0.000 claims description 4
- 238000002604 ultrasonography Methods 0.000 claims description 2
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims 1
- 238000004945 emulsification Methods 0.000 abstract description 3
- 238000013268 sustained release Methods 0.000 abstract description 3
- 239000012730 sustained-release form Substances 0.000 abstract description 3
- 231100000419 toxicity Toxicity 0.000 abstract description 3
- 230000001988 toxicity Effects 0.000 abstract description 3
- 239000002699 waste material Substances 0.000 abstract description 3
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 7
- 230000000694 effects Effects 0.000 description 7
- 239000000243 solution Substances 0.000 description 7
- 239000003814 drug Substances 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
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
- 229940079593 drug Drugs 0.000 description 3
- 238000002347 injection Methods 0.000 description 3
- 239000007924 injection Substances 0.000 description 3
- 244000144972 livestock Species 0.000 description 3
- 239000000463 material Substances 0.000 description 3
- 206010067484 Adverse reaction Diseases 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- 241000894006 Bacteria Species 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- 230000006838 adverse reaction Effects 0.000 description 2
- 210000001072 colon Anatomy 0.000 description 2
- 230000000857 drug effect Effects 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 238000001914 filtration Methods 0.000 description 2
- 238000004108 freeze drying Methods 0.000 description 2
- 239000007800 oxidant agent Substances 0.000 description 2
- 230000001590 oxidative effect Effects 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
- 238000001179 sorption measurement Methods 0.000 description 2
- RWRDLPDLKQPQOW-UHFFFAOYSA-N tetrahydropyrrole Natural products C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 2
- 231100000331 toxic Toxicity 0.000 description 2
- 230000002588 toxic effect Effects 0.000 description 2
- 241001662103 Cryptocarya corrugata Species 0.000 description 1
- 238000009825 accumulation Methods 0.000 description 1
- 239000003929 acidic solution Substances 0.000 description 1
- 239000002156 adsorbate Substances 0.000 description 1
- 239000012670 alkaline solution Substances 0.000 description 1
- 230000000844 anti-bacterial effect Effects 0.000 description 1
- 230000001580 bacterial effect Effects 0.000 description 1
- 239000000022 bacteriostatic agent Substances 0.000 description 1
- 210000004027 cell Anatomy 0.000 description 1
- 238000002485 combustion reaction Methods 0.000 description 1
- 230000007812 deficiency Effects 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- 238000005538 encapsulation Methods 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 238000004880 explosion Methods 0.000 description 1
- 239000002360 explosive Substances 0.000 description 1
- 239000003292 glue Substances 0.000 description 1
- 150000004676 glycans Chemical class 0.000 description 1
- BXWNKGSJHAJOGX-UHFFFAOYSA-N hexadecan-1-ol Chemical compound CCCCCCCCCCCCCCCCO BXWNKGSJHAJOGX-UHFFFAOYSA-N 0.000 description 1
- 208000021760 high fever Diseases 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
- 239000002075 main ingredient Substances 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 239000012982 microporous membrane Substances 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 210000004400 mucous membrane Anatomy 0.000 description 1
- 229910052757 nitrogen Inorganic materials 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
- 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
- 230000001954 sterilising effect Effects 0.000 description 1
- 238000004659 sterilization and disinfection Methods 0.000 description 1
- 230000000638 stimulation Effects 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 238000013269 sustained drug release Methods 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 230000014616 translation Effects 0.000 description 1
- 238000000108 ultra-filtration Methods 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 present invention relates to a kind of gelatin-compounded microballoons of lincomycin carboxymethyl chitosan and preparation method thereof, which is prepared by the method included the following steps：Prepare the normal saline solution for the carboxymethyl chitosan sugar-gelatin that mass concentration is 1.5% 3.0%, it is ultrasonically treated 7 10min and lincomycin is added after being sufficiently stirred, solution after mixing is added in the atoleine containing Span80,1h is stirred with rotating speed 500r/min；Glutaraldehyde cross-linking solidification 2h is added, then is filtered through sand core funnel；It is alternately washed with petroleum ether and isopropanol, it washs 4 times altogether, in 45 DEG C of vacuum drying chambers after dry 8h, obtain lincomycin carboxymethyl chitosan gelatine microsphere, with the carboxymethyl chitosan of good biocompatibility and gelatin for main waste lincomycin microballoon, it does not have toxicity, and biodegradable, has preferable sustained release performance after emulsification and cross linked.
Description
Technical field
The present invention relates to field of pharmaceutical preparations, in particular it relates to a kind of lincomycin carboxymethyl chitosan-gelatin
Complex microsphere and preparation method thereof.
Background technology
Lincomycin (Lincomycin Hydrochloride), (also referred to as Lincomycin Hydrochloride), entitled 6- (the 1- first of chemistry
The trans- 4- propyl-L-2- pyrrolidine formyls amino of base -) -1- is thio-the pungent pyranoside of 6,8- dideoxy-D- erythro form-α-D- galas
Hydrochloride monohydrate.Lincomycin is white crystalline powder；Have micro- smelly or special smelly；Bitter.Lincomycin is in water or first
It is readily soluble in alcohol, it is slightly molten in ethanol.Lincomycin acts on the ribosomal 50S subunits of sensitive bacteria, prevents the extension of peptide chain, to
Inhibit the protein synthesis of bacterial cell.Lincomycin is generally bacteriostatic agent, but in higher concentrations, is also had to highly sensitive bacterium
There is bactericidal effect.
CN102000036A patent applications disclose a kind of method for preparing colon targeted pill of lincomycin that livestock and poultry use,
Use lincomycin as main ingredient, using blank piller, wrap respectively medicine layer-lincomycin, 8% block layer-hexadecanol,
2% time lag layer-HPMC, 15%pH sensitive membranes-EudragitS100 prepare the colon targeted pill of lincomycin that livestock and poultry use.
Auxiliary material hexadecanol used in the product has stimulation to eyes, skin, mucous membrane and the upper respiratory tract, harmful to environment, right
Water body can pollute, and powder can form explosive mixture with air, meet open fire, high fever or contacted with oxidant, have and cause
The danger of combustion explosion.
CN102000036A patent applications disclose a kind of lincomycin hydrochloride freeze-dried powder injection for livestock injection and its system
Preparation Method, the Lincomycin Hydrochloride freeze drying powder injection include following components：Lincomycin Hydrochloride 3%~30%；Excipient 0.1%
~90%；Additives 0.1%~90%.Preparation method includes：In an aseptic environment, water for injection is taken, is protected from light and hydrochloric acid woods is added
Can mycin and recipe quantity excipient, be sufficiently stirred dissolving；Additives are added and adjust pH value between 4.0~6.5；At ultrafiltration
Reason is added medicinal carbon stirring and adsorbing and removes pyrogen removal；Through 0.45 μm of filtering with microporous membrane, constant volume；0.22 μm of miillpore filter end
Hold filtration sterilization；Nitrogen charging dispense, freeze-drying, roll lid be sealed to get.Auxiliary material medicine used in the preparation method of the product
There is certain combustibility with activated carbon, may catch fire cause to burn in air.Activated carbon can not be mixed with oxidant to be made
With activated carbon in alkaline solution generally in an acidic solution than having higher adsorption rate, pH value that can in water be deposited to adsorbate
State and solubility etc. have an impact, to influence adsorption effect.
It is larger to there is auxiliary material side effect in lincomycin medicament in the prior art more, cannot be biodegradable, it cannot be effective
Reduce the toxicity and the unconspicuous problem of sustained drug release effect of drug.
Invention content
The technical problem to be solved by the present invention is to overcome the deficiencies in the prior art, with the carboxymethyl shell of good biocompatibility
Glycan and gelatin are main waste lincomycin microballoon, it does not have toxicity, and biodegradable, have after emulsification and cross linked compared with
Good sustained release performance.It can reduce adverse reaction of the drug to body, reduce toxic side effect, to extend drug effect, improve treatment
Effect selects the optimised process for preparing lincomycin carboxymethyl chitosan-gelatin-compounded microballoon by experiment.
The technical solution adopted by the present invention is：
The present invention provides a kind of lincomycin carboxymethyl chitosan-gelatin-compounded microballoon, the microballoon is by including walking as follows
Rapid method is prepared：The normal saline solution for carboxymethyl chitosan-gelatin that mass concentration is 1.5%-3.0% is prepared,
It is ultrasonically treated 7-10min and lincomycin is added after being sufficiently stirred, solution after mixing is added to containing 1.5%-
In the atoleine of 2.5% (volume fraction) Span80,1h is stirred with rotating speed 500r/min；Add glutaraldehyde cross-linking solidification
2h, then filtered through sand core funnel；It is alternately washed with petroleum ether and isopropanol, is washed 4 times altogether, it is dry in 45 DEG C of vacuum drying chambers
After 8h, lincomycin carboxymethyl chitosan-gelatine microsphere is obtained.Wherein the additive amount of carboxymethyl chitosan-gelatin is lincomycin
1-2 times of quality；Crosslinking agent glutaraldehyde:Carboxymethyl chitosan-gelatin=8-12mL：1g；Contain 1.5%-2.5% (volumes point
Number) Span80 atoleine：Lincomycin=120mL:1g.
Preferably, the mass ratio of the carboxymethyl chitosan and gelatin is 1：1.
Preferably, the mass concentration of the carboxymethyl chitosan-gelatin is 2%, the addition of carboxymethyl chitosan-gelatin
Amount is 1.5 times of lincomycin quality；Glutaraldehyde：Carboxymethyl chitosan-gelatin=10mL：1g.Span80 volume fractions are
2.0%.
The present invention also provides a kind of preparation method of lincomycin carboxymethyl chitosan-gelatin-compounded microballoon, this method
Include the following steps：Prepare the normal saline solution for carboxymethyl chitosan-gelatin that mass concentration is 1.5%-3.0%, ultrasound
It handles 7-10min and lincomycin is added after being sufficiently stirred, solution after mixing is added to containing 1.5%-2.5%
In the atoleine of (volume fraction) Span80,1h is stirred with rotating speed 500r/min；Glutaraldehyde cross-linking solidification 2h is added, then is passed through
Sand core funnel filters；It is alternately washed with petroleum ether and isopropanol, is washed 4 times altogether, in 45 DEG C of vacuum drying chambers after dry 8h, obtained
Lincomycin carboxymethyl chitosan-gelatine microsphere.Wherein the additive amount of carboxymethyl chitosan-gelatin is the 1- of lincomycin quality
2 times；Crosslinking agent glutaraldehyde:Carboxymethyl chitosan-gelatin=8-12mL：1g；Contain 1.5%-2.5% (volume fraction) Span80
Atoleine：Lincomycin=120mL:1g.
In the above method, it is preferable that the mass ratio of the carboxymethyl chitosan and gelatin is 1：1.
In the above method, it is preferable that the mass concentration of the carboxymethyl chitosan-gelatin is 2%, carboxymethyl chitosan
The additive amount of sugar-gelatin is 1.5 times of lincomycin quality；Glutaraldehyde：Carboxymethyl chitosan-gelatin=10mL：1g.Span80
Volume fraction is 2.0%.
Advantageous effect possessed by the present invention：
With the carboxymethyl chitosan of good biocompatibility and gelatin for main waste lincomycin microballoon, it is without poison
Property, and it is biodegradable, there is preferable sustained release performance after emulsification and cross linked.It can reduce adverse reaction of the drug to body,
Toxic side effect is reduced, to extend drug effect, improves therapeutic effect.
Specific implementation mode
The present invention is further explained in the light of specific embodiments, but does not limit protection scope of the present invention.
A kind of preparation method of lincomycin carboxymethyl chitosan-gelatin-compounded microballoon, this method comprises the following steps：
The normal saline solution of carboxymethyl chitosan-gelatin is prepared, being ultrasonically treated 8min and woods is added after being sufficiently stirred can
Solution after mixing is added in the atoleine containing Span80 by mycin, and 1h is stirred with rotating speed 500r/min；Again plus
Enter glutaraldehyde cross-linking solidification 2h, then is filtered through sand core funnel；It is alternately washed, is washed 4 times altogether, at 45 DEG C with petroleum ether and isopropanol
In vacuum drying chamber after dry 8h, lincomycin carboxymethyl chitosan-gelatine microsphere is obtained.The wherein described carboxymethyl chitosan with it is bright
The mass ratio of glue is 1：1, the atoleine containing 1.5%-2.5% (volume fraction) Span80：Lincomycin=120mL:1g.
Microballoon is prepared according to parameter in above-mentioned table, by extracorporeal releasing experiment it is found that lincomycin bulk pharmaceutical chemicals are in 50min
Release finishes, and lincomycin carboxymethyl chitosan-gelatine microsphere prepared by embodiment 1-9 is in pH6.8 phosphate buffers
Accumulation dissolution 100% after 10h.
It can be seen that the drugloading rate of lincomycin carboxymethyl chitosan-gelatine microsphere in embodiment 2 by embodiment 1-9
Reach 75% with encapsulation rate.Best results prepare microballoon, drugloading rate and encapsulating in triplicate according to the process conditions of embodiment 2
Rate is respectively 74.97%, 75.91%, 75.58%, and preparation process reproducibility is preferable.
Claims (6)
1. a kind of lincomycin carboxymethyl chitosan-gelatin-compounded microballoon, it is characterised in that：The microballoon is by including the following steps
Method is prepared：Prepare the normal saline solution for carboxymethyl chitosan-gelatin that mass concentration is 1.5%-3.0%, ultrasound
It handles 7-10min and lincomycin is added after being sufficiently stirred, solution after mixing is added to containing volume fraction
In the atoleine of 1.5%-2.5%Span80,1h is stirred with rotating speed 500r/min；Glutaraldehyde cross-linking solidification 2h is added, then
It is filtered through sand core funnel；It is alternately washed with petroleum ether and isopropanol, is washed 4 times altogether, in 45 DEG C of vacuum drying chambers after dry 8h,
Lincomycin carboxymethyl chitosan-gelatine microsphere is obtained, the wherein additive amount of carboxymethyl chitosan-gelatin is lincomycin quality
1-2 times；Crosslinking agent glutaraldehyde:Carboxymethyl chitosan-gelatin=8-12mL：1g；Contain volume fraction 1.5%-2.5%Span80
Atoleine：Lincomycin=120mL:1g.
2. a kind of lincomycin carboxymethyl chitosan-gelatin-compounded microballoon according to claim 1, it is characterised in that：It is described
The mass ratio of carboxymethyl chitosan and gelatin is 1：1.
3. a kind of lincomycin carboxymethyl chitosan-gelatin-compounded microballoon according to claim 1 or claim 2, it is characterised in that：Institute
The mass concentration for the carboxymethyl chitosan-gelatin stated is 2%, and the additive amount of carboxymethyl chitosan-gelatin is lincomycin quality
1.5 times；Glutaraldehyde：Carboxymethyl chitosan-gelatin=10mL：1g, Span80 volume fraction are 2.0%.
4. a kind of preparation method of lincomycin carboxymethyl chitosan-gelatin-compounded microballoon, it is characterised in that：This method includes such as
Lower step：The normal saline solution for preparing carboxymethyl chitosan-gelatin that mass concentration is 1.5%-3.0%, is ultrasonically treated 7-
Simultaneously lincomycin is added after being sufficiently stirred in 10min, and solution after mixing is added to containing volume fraction 1.5%-2.5%
In the atoleine of Span80,1h is stirred with rotating speed 500r/min；Glutaraldehyde cross-linking solidification 2h is added, then is taken out through sand core funnel
Filter；It is alternately washed with petroleum ether and isopropanol, is washed 4 times altogether, in 45 DEG C of vacuum drying chambers after dry 8h, obtain lincomycin carboxylic
Methyl chitosan-gelatine microsphere.Wherein the additive amount of carboxymethyl chitosan-gelatin is 1-2 times of lincomycin quality；Crosslinking agent
Glutaraldehyde:Carboxymethyl chitosan-gelatin=8-12mL：1g；Atoleine containing volume fraction 1.5%-2.5%Span80：
Lincomycin=120mL:1g.
5. the preparation method of a kind of lincomycin carboxymethyl chitosan-gelatin-compounded microballoon according to claim 4, feature
It is：The mass ratio of the carboxymethyl chitosan and gelatin is 1：1.
6. the preparation method of a kind of lincomycin carboxymethyl chitosan-gelatin-compounded microballoon according to claim 4 or 5,
It is characterized in that：The mass concentration of the carboxymethyl chitosan-gelatin is 2%, and the additive amount of carboxymethyl chitosan-gelatin is woods
It can be 1.5 times of mycin quality；Glutaraldehyde：Carboxymethyl chitosan-gelatin=10mL：1g, Span80 volume fraction are 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 CN105796505A (en) | 2016-07-27 |
| CN105796505B true 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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Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| 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 |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AU2003303525A1 (en) * | 2002-12-31 | 2004-07-29 | Ultra-Sonic Technologies, L.L.C. | Transdermal delivery using encapsulated agent activated by ultrasound and/or heat |
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2016
- 2016-03-18 CN CN201610158149.1A patent/CN105796505B/en not_active Expired - Fee Related
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
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