CN108143720A - Anti-infectious sustained release pharmaceutical composition of biodegradation type hemostasis and preparation method thereof - Google Patents
Anti-infectious sustained release pharmaceutical composition of biodegradation type hemostasis and preparation method thereof Download PDFInfo
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- CN108143720A CN108143720A CN201611096328.3A CN201611096328A CN108143720A CN 108143720 A CN108143720 A CN 108143720A CN 201611096328 A CN201611096328 A CN 201611096328A CN 108143720 A CN108143720 A CN 108143720A
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0019—Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
- A61K9/0024—Solid, semi-solid or solidifying implants, which are implanted or injected in body tissue
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0002—Galenical forms characterised by the drug release technique; Application systems commanded by energy
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/14—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
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/14—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
- A61K9/1682—Processes
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
- A61K9/50—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
- A61K9/5005—Wall or coating material
- A61K9/5021—Organic macromolecular compounds
- A61K9/5031—Organic macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyethylene glycol, poly(lactide-co-glycolide)
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
- A61K9/50—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
- A61K9/5005—Wall or coating material
- A61K9/5021—Organic macromolecular compounds
- A61K9/5036—Polysaccharides, e.g. gums, alginate; Cyclodextrin
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Abstract
The invention discloses anti-infectious slow releasing pharmaceutical combinations of a kind of biodegradation type hemostasis and preparation method thereof.Its main component includes, antibiotic, chitosan oligosaccharide, chitosan.Key technical problem to be solved by this invention is to develop anti-infectious slow releasing pharmaceutical combination of a kind of biodegradation type hemostasis and preparation method thereof.So as to effectively solve the problems, such as antibiotic implantation preparation in control release, biodegradable, raising medicine stability.
Description
Technical field
The present invention relates to hemostasis and antibiotic medicine, and in particular to the anti-infectious slow releasing pharmaceutical group of biodegradation type hemostasis
Conjunction and preparation method thereof is a kind of using hemostatic material and antibiotic as implant pellet of main ingredient and preparation method thereof.
Background technology
Severe local tissue infection such as chronic osteomyelitis, alveolitis, Soft Tissue Abscess: An Experimental etc. are infected by suppurative bacterium
Caused diseases associated with inflammation, majority are caused by Hematogenous infection or trauma infection contamination and postoperative infection.Such inflammation is mostly with skin
Ulceration forms one or more sinus, discharges fester, recurrent exerbation repeatedly, it is difficult to cure, great pain is brought to patient.By
Inflammation surrounding tissue is not more caused to form hardening barrier in chronic inflammation delay, systemic administration is difficult to reach affected part, lacks at present
Efficiently, wide spectrum, can be directly used for the drug of lesion.
There are many currently used Antibiotics, there is aminoaglycon antibiotics, glycopeptide antibiotics, beta-lactam antibiosis
Element, carbostyril antibiotic etc., administering mode are mainly the oral Formulations for systemic administration mode with injection.But the mode of Formulations for systemic administration
All kinds of corrupt practices creep in：First, drug absorption problem.Since chronic inflammation delay does not more cause inflammation surrounding tissue to form hardening screen
Barrier, systemic administration are difficult to reach affected part.As aminoaglycon antibiotics gentamicin, kanamycins need a large amount of uses can be only achieved
Effective antibiotics concentration.Secondly, drug transport, metabolic problems.Since lesions position blood flow is few, such as blood flow is few to the marrow, and medicine
Object have passed through the destruction of internal many degradation mechanisms, even if large dosage uses antibiotic, it is also difficult into inner disease foci formation office to the marrow
Portion's high concentration.Again, Formulations for systemic administration toxic side effect is very big.(it is more than 10mg/ as the injection of glycopeptide antibiotics vancomycin is too fast
Min speed instils) or liquid overrich (blood concentration higher than 60 μ g/ml be poisoning concentration), easily cause ototoxicity, renal toxicity,
Allergic rash and phlebitis etc..Thus, it is badly in need of a kind of part, controlled release drug administration dosage form at present.
Implant refers to drug implantation body foci position or subcutaneous, and slow, control discharges, the drug of long-term role
Preparation.Implant improves curative effect by improving the drug concentration of lesions position, extending the action time of drug and pathological tissues,
Meanwhile Systemic reaction is reduced or eliminated for medicine by being reduced or avoided to whole body normal structure.Therefore, needle of the present invention
To problem above, using antibiotic as main ingredient, a kind of novel degradable pharmaceutical carrier, slow release drug, so as to carry are designed
The effect of high antibiotic formulations.
Due to implant carrier by carry peptide medicament be directly entered lesion tissue, carrier material must have
Good biocompatibility and biological degradability.Relative to synthesis macromolecule (aliphatic polyester, polyethylene glycol) etc. biomaterials,
Chitosan not only derives from a wealth of sources for the natural polysaccharide of representative, is cheap and easy to get, has good biocompatibility, biological degradability,
The advantage of being also equipped with has：1. adjust acid-base balance：Modern medicine study shows under wound, inflammation, and acyclic acidic is presented in vivo
Border.The catabolite of chitosan is chitosan oligosaccharide, acetyl-Glucosamine, since molecule is in positive electricity, shows alkalinity, can adjust disease
Disease position acid-base balance；Neutralize damage of the acid product to tissue；Be conducive to increase the stability of drug；It creates one and promotes wound
The environmental condition of the healing of mouth.2. promote to repair：Research shows that the catabolite gucosamine inherently human body of chitosan is thin
Important component in born of the same parents can repair the sugar chain of defect, restore the normal function of damaged cell, may advantageously facilitate repairing for body
It is multiple.It is 3. antibacterial：Chitosan has extensive bacteriostasis, advantageously reduces the generation infected in implant surgery.
As previously mentioned, chitosan has many advantages as implantation material, however, by antibiotic and the compound preparation of chitosan
It is also limited into implant by following several respects：1. preparation process problem.Implantation preparation moulding process almost all is breast at present
Change method, main problem are largely to use pharmaceutical activity caused by organic solvent, intense mechanical shearing to lose and foreseeable
Environmental pollution.Meanwhile the cumbersome postprocessing working procedures of emulsion process technique are also one of low restrictive factors of preparation efficiency；In addition,
Technique causes entrapment efficiency low at present.Thus, how to reach high encapsulation rate, the preparations shaping technique of high activity, improve drug
Stability is also one of critical issue that implantation preparation faces.2. control release problem.Some antibiotic strong antibacterials, effectively
Dosage is small, how to ensure that release amount of medicine and the validity of release time are also implant urgent problem to be solved.
Thus, the technical problems to be solved by the invention are to develop a kind of anti-infectious slow releasing medicinal of biodegradation type hemostasis
Object combination and preparation method thereof.So as to effectively solve antibiotic implantation preparation control release, it is biodegradable, improve drug it is steady
The problem of qualitative.
Invention content
The purpose of the present invention is anti-infectious slow releasing pharmaceutical combinations of a kind of biodegradation type hemostasis and preparation method thereof.
Biodegradation type stops blooding anti-infectious sustained release pharmaceutical composition, sustained release pharmaceutical composition preparation for medicated pellet or
It is made of medicated pellet and coatings, medicated pellet is made of antibiotic, carrier material and adhesive, it is characterised in that：By matter
Measure number meter, 5~30 parts of antibiotic, carrier material, 10-15 parts of chitosan oligosaccharide, 15~65 parts of chitosan, 30~70 parts of adhesive；
0-10 parts of coatings.
Medicated pellet, 0.5≤d of average grain diameter≤1mm of pellet, pellet hardness are prepared using extrusion-spheronization
0.5-2kg, pellet density 1.2-1.8g/cm3。
The antibiotic is aminoaglycon antibiotics (one kind in such as gentamicin, kanamycins, clindamycin or two kinds
More than), glycopeptide antibiotics (one or two or more kinds in such as teicoplanin, vancomycin), beta-lactam antibiotic (such as
Amoxicillin), carbostyril antibiotic (one or two or more kinds in such as Ciprofloxacin, Moxifloxacin), macrolides resist
Raw element (such as erythromycin) one or two or more kinds of drugs therein.
Described adhesive is ethyl alcohol, water, glycerine .01-0.4mol/L acetic acid aqueous solutions, volumetric concentration 0.1%-50% second
One or more of alcohol solution composition.
The material of the coatings is one or more of lactic acid polymer, lactic acid-ethanol copolymer, chitosan group
Into.
The molecular weight (Mw) of the chitosan：5KD~500KD, deacetylation (DD%)：50~100%.
The molecular weight (Mw) of the chitosan oligosaccharide：2KD~3KD, deacetylation (DD%)：50~100%.
The preparation method of any implant pellet, it is characterised in that：
1) medicated pellet is prepared using extrusion-spheronization：Antibiotic, carrier material, bonding agent composition are placed in
Medicated pellet is made in extruded, round as a ball process in extrusion spheronization machine；
2) obtained medicated pellet is dried；
3) coating material is dissolved in solvent and coating solution is made；Using fluidized bed coating equipment, coating solution is loaded on and is contained
Outside medicine pellet, the medicated pellet containing coatings is made.
Extrusion the rotating speed 10rpm~50rpm, round as a ball rotating speed 400rpm~2000rpm of extrusion spheronization machine in the step 1)；
Step 2) the drying means is in spray drying, fluidized bed drying, vacuum drying, air dry oven drying means
One kind.
Coating solution in the step 3), the solvent of lactic acid polymer is one kind in acetone or dichloromethane or two kinds；Lactic acid-
The solvent of ethanol copolymer is one kind in acetone or dichloromethane or two kinds；Chitosan solvent is in water or acetic acid aqueous solution
It is a kind of.
It is biodegradable that the characteristics of biodegradation type antibiotic implantation preparation of the present invention, is that material therefor is
Material, another feature be the present invention for slow release pharmaceutical preparation, antibiotic can be in lesions position slow release.
The preparation method of the implant preparation of biodegradation type slow release antibiotic according to the present invention is as follows：
1. antibiotic bulk pharmaceutical chemicals are weighed, carrier material chitosan oligosaccharide, chitosan, calcium phosphate, by carrier material one or more
It is uniformly mixed in blender, and is slowly added to binder while stirring in platinum is ground, obtain that there is certain humidity and elasticity
Softwood.Low temperature extrusion spheronization machine is opened, with certain extrusion temperature and to squeeze out rotating speed extrusion, then by extrudate in spheronizator
In with round as a ball balling-up under conditions of certain rotating speed.2. collecting bead, and put it into air dry oven and dry to constant weight.
Dry microballoon is put into the hermetic bag with drier, is stored in 4 DEG C of refrigerators.3. microballoon prepared by the above method exists
It is coated in fluid bed.Certain density coating solution is prepared, is coated with a certain concentration, coating temperature and Coating times.
Extrusion the rotating speed 10rpm~50rpm, round as a ball rotating speed 400rpm~2000rpm of step 1. middle extrusion spheronization machine.Step
2. drying means is one kind in spray drying, fluidized bed drying, vacuum drying, air dry oven drying means.Step 3. in
The solvent of lactic acid polymer is a kind of in acetone or dichloromethane；The solvent of lactic acid-ethanol copolymer is acetone or dichloromethane
It is a kind of in alkane；Chitosan solvent is one kind in water or acetic acid aqueous solution.
The present invention can increase the density of pellet using extrusion-method for rolling circle, improve hardness；
Wherein, microballoon hardness is reduced with the reduction of deacetylating degree of chitosan；Microballoon hardness is with microballoon drugloading rate
It increases and reduces；Microballoon hardness is increased with the reduction of chitosan molecule amount；Microballoon is hard under the conditions of prescription ratio of the present invention
Degree is up to 0.5-2kg.
Wherein, microballoon Microsphere Density is reduced with the reduction of deacetylating degree of chitosan；Microsphere Density carries medicine with microballoon
The reduction of amount and reduce；Microsphere Density is increased with the reduction of chitosan molecule amount；It is micro- under the conditions of prescription ratio of the present invention
Ball density is up to 1.2-1.8g/cm3。
The method obtains degradable slow release antibiotic implantation preparation process stabilizing, easy to operation, suitable work
Industry metaplasia is produced.
The advantageous effect of implantation preparation of the present invention and preparation method thereof is：
1. the pharmaceutical carrier used in the present invention is chitosan oligosaccharide and chitosan.Carrier has good biocompatibility and biology
Degradability.Chitosan oligosaccharide, chitosan not only derive from a wealth of sources for the natural polysaccharide of representative, are cheap and easy to get, have good bio-compatible
Property, biological degradability, the advantage of being also equipped with have：1. adjust acid-base balance：Modern medicine study shows under wound, inflammation, in vivo
Acidic environment is presented.The catabolite of chitosan is chitosan oligosaccharide, acetyl-Glucosamine, since molecule is in positive electricity, shows alkali
Property, affected site acid-base balance can be adjusted；Neutralize damage of the acid product to tissue；Be conducive to increase the stability of drug；
Create the environmental condition of the healing of a promotion wound.2. promote to repair：Research shows that the catabolite gucosamine of chitosan
Important component inherently in human body cell can repair the sugar chain of defect, restore the normal function of damaged cell, favorably
In the reparation for promoting body.It is 3. antibacterial：Chitosan has extensive bacteriostasis, advantageously reduces the hair infected in implant surgery
It is raw.
2. the preparation process almost all currently for antibiotic implantation preparation is emulsion process.This method main problem is
Pharmaceutical activity caused by largely being sheared using organic solvent, intense mechanical is lost.Although other patented methods use natural polysaccharide
Material (such as chitosan, starch), but microballoon is mainly prepared by spray drying in preparations shaping technique, it then will be pre-
The microballoon first prepared is placed in absorption in drug solution and carries medicine, and main problem is that entrapment efficiency is low, it is difficult to adapt to actual production
Requirement.Using extrusion-method for rolling circle, high encapsulation rate, high activity for drug have a clear superiority, make simultaneously the present invention
Pellet density obtained is larger, hardness is higher, is conducive to drug controlled release.
Meanwhile extrusion-method for rolling circle requires combustion more harshness, only using the ratio of present invention composition prescription
Example range is just applicable to extrusion-spheronization process, and then is likely to the pellet preparations for being shaped to be suitble to implantation application, protects simultaneously
Card pellet has higher density and hardness.
3. prescription of the present invention is reasonable, only the micro- of higher hardness can be just formed in present invention composition prescription proportional region
Ball, pellet mobility and fillibility are good, convenient for clinical practice.
4. drug release durations are long, drug releasing rate is uniform.
Specific embodiment
The present invention is further described in conjunction with the embodiments below：
Embodiment 1
Weigh penicillin 10g, chitosan oligosaccharide 10g (DD%=94%, Mw=1KD cross 200 mesh), chitosan 40g (DD%=
94%, Mw=100KD cross 200 mesh), three is uniformly mixed, and be slowly added to 70 while stirring in platinum is ground in blender
~100ml deionized waters obtain the softwood with certain humidity and elasticity, and softwood are sealed up for safekeeping, are transferred in 20~30 DEG C of conditions
Put 6~12h.Mini250 low temperature extrusion spheronization machines are opened, 10 DEG C of extrusion temperature is squeezed out with the extrusion rotating speed of 20rpm, round as a ball
Machine rotating speed be 800rpm under conditions of through the round as a ball balling-up of 2min.Bead is collected, and is put it into dry in 30 DEG C of air dry ovens
6h is to constant weight.Dry microballoon is put into the hermetic bag with drier, is stored in 4 DEG C of refrigerators.Grain size, hardness,
Density
Embodiment 2
Weigh erythromycin 10g, chitosan oligosaccharide 15g (DD%=94%, Mw=2KD cross 200 mesh), chitosan 40g (DD%=
94%, Mw=100KD cross 200 mesh), three is uniformly mixed, and be slowly added to 70 while stirring in platinum is ground in blender
~100ml deionized waters obtain the softwood with certain humidity and elasticity, and softwood are sealed up for safekeeping, are transferred in 20~30 DEG C of conditions
Put 6~12h.Mini250 low temperature extrusion spheronization machines are opened, 10 DEG C of extrusion temperature is squeezed out with the extrusion rotating speed of 20rpm, round as a ball
Machine rotating speed be 800rpm under conditions of through the round as a ball balling-up of 5min.Bead is collected, and is put it into dry in 30 DEG C of air dry ovens
6h is to constant weight.Dry microballoon is put into the hermetic bag with drier, is stored in 4 DEG C of refrigerators.
Embodiment 3
Weigh penicillin 10g, chitosan oligosaccharide 12g (DD%=94%, Mw=1KD cross 200 mesh), chitosan 40g (DD%=
94%, Mw=100KD cross 200 mesh), three is uniformly mixed, and be slowly added to 70 while stirring in platinum is ground in blender
~100ml deionized waters obtain the softwood with certain humidity and elasticity, and softwood are sealed up for safekeeping, are transferred in 20~30 DEG C of conditions
Put 6~12h.Mini250 low temperature extrusion spheronization machines are opened, 10 DEG C of extrusion temperature is squeezed out with the extrusion rotating speed of 20rpm, round as a ball
Machine rotating speed be 800rpm under conditions of through the round as a ball balling-up of 10min.Bead is collected, and is put it into dry in 30 DEG C of air dry ovens
6h is to constant weight.Dry microballoon is put into the hermetic bag with drier, is stored in 4 DEG C of refrigerators.
Embodiment 4
Weigh kanamycins 10g, chitosan oligosaccharide 15g (DD%=94%, Mw=2KD cross 200 mesh), chitosan 60g (DD%
=94%, Mw=100KD cross 200 mesh), three is uniformly mixed, and be slowly added to while stirring in platinum is ground in blender
70~100ml deionized waters obtain the softwood with certain humidity and elasticity, and softwood are sealed up for safekeeping, under the conditions of 20~30 DEG C
Place 6~12h.Mini250 low temperature extrusion spheronization machines are opened, 10 DEG C of extrusion temperature is squeezed out with the extrusion rotating speed of 20rpm, rolled
Circular knitting machine rotating speed be 1000rpm under conditions of through the round as a ball balling-up of 2min.Bead is collected, and puts it into 30 DEG C of air dry ovens and does
Dry 6h is to constant weight.Dry microballoon is put into the hermetic bag with drier, is stored in 4 DEG C of refrigerators.
Embodiment 5
Weigh Amoxicillin 10g, chitosan oligosaccharide 15g (DD%=94%, Mw=2KD cross 200 mesh), chitosan 60g (DD%
=94%, Mw=100KD cross 200 mesh), three is uniformly mixed, and be slowly added to while stirring in platinum is ground in blender
70~100ml deionized waters obtain the softwood with certain humidity and elasticity, and softwood are sealed up for safekeeping, under the conditions of 20~30 DEG C
Place 6~12h.Mini250 low temperature extrusion spheronization machines are opened, 10 DEG C of extrusion temperature is squeezed out with the extrusion rotating speed of 20rpm, rolled
Circular knitting machine rotating speed be 1000rpm under conditions of through the round as a ball balling-up of 5min.Bead is collected, and puts it into 30 DEG C of air dry ovens and does
Dry 6h is to constant weight.Dry microballoon is put into the hermetic bag with drier, is stored in 4 DEG C of refrigerators.
Embodiment 6
Weigh gentamicin 10g, chitosan oligosaccharide 15g (DD%=94%, Mw=2KD cross 200 mesh), chitosan 60g (DD%
=94%, Mw=100KD cross 200 mesh), three is uniformly mixed, and be slowly added to while stirring in platinum is ground in blender
70~100ml deionized waters obtain the softwood with certain humidity and elasticity, and softwood are sealed up for safekeeping, under the conditions of 20~30 DEG C
Place 6~12h.Mini250 low temperature extrusion spheronization machines are opened, 10 DEG C of extrusion temperature is squeezed out with the extrusion rotating speed of 20rpm, rolled
Circular knitting machine rotating speed be 1000rpm under conditions of through the round as a ball balling-up of 10min.Bead is collected, and is put it into 30 DEG C of air dry ovens
6h is dried to constant weight.Dry microballoon is put into the hermetic bag with drier, is stored in 4 DEG C of refrigerators.
Embodiment 7
Weigh penicillin 10g, chitosan oligosaccharide 15g (DD%=94%, Mw=2KD cross 200 mesh), chitosan 60g (DD%=
94%, Mw=100KD cross 200 mesh), three is uniformly mixed, and be slowly added to 70 while stirring in platinum is ground in blender
~100ml deionized waters obtain the softwood with certain humidity and elasticity, and softwood are sealed up for safekeeping, are transferred in 20~30 DEG C of conditions
Put 6~12h.Mini250 low temperature extrusion spheronization machines are opened, 10 DEG C of extrusion temperature is squeezed out with the extrusion rotating speed of 20rpm, round as a ball
Machine rotating speed be 1200rpm under conditions of through the round as a ball balling-up of 2min.Bead is collected, and is put it into dry in 30 DEG C of air dry ovens
6h is to constant weight.Dry microballoon is put into the hermetic bag with drier, is stored in 4 DEG C of refrigerators.
Embodiment 8
Weigh Moxifloxacin 10g, chitosan oligosaccharide 10g (DD%=94%, Mw=2KD cross 200 mesh), chitosan 40g (DD%
=94%, Mw=100KD cross 200 mesh), three is uniformly mixed, and be slowly added to while stirring in platinum is ground in blender
70~100ml deionized waters obtain the softwood with certain humidity and elasticity, and softwood are sealed up for safekeeping, under the conditions of 20~30 DEG C
Place 6~12h.Mini250 low temperature extrusion spheronization machines are opened, 10 DEG C of extrusion temperature is squeezed out with the extrusion rotating speed of 20rpm, rolled
Circular knitting machine rotating speed be 1200rpm under conditions of through the round as a ball balling-up of 5min.Bead is collected, and puts it into 30 DEG C of air dry ovens and does
Dry 6h is to constant weight.Dry microballoon is put into the hermetic bag with drier, is stored in 4 DEG C of refrigerators.
Claims (10)
- The anti-infectious sustained release pharmaceutical composition 1. biodegradation type stops blooding, sustained release pharmaceutical composition preparation for medicated pellet or by Medicated pellet and coatings composition, medicated pellet are made of antibiotic, carrier material and adhesive, it is characterised in that：By quality Number meter, 5~30 parts of antibiotic, carrier material, 10-15 parts of chitosan oligosaccharide, 15~65 parts of chitosan, 30~70 parts of adhesive；Packet 0-10 parts of clothing layer.
- 2. sustained release pharmaceutical composition described in accordance with the claim 1, it is characterised in that：It is prepared and contained using extrusion-spheronization Medicine pellet, 0.5≤d of average grain diameter≤1mm of pellet, pellet hardness 0.5-2kg, pellet density 1.2-1.8g/cm3。
- 3. sustained release pharmaceutical composition described in accordance with the claim 1, it is characterised in that：The antibiotic is aminoaglycon antibiotics (one or two or more kinds in such as gentamicin, kanamycins, clindamycin), glycopeptide antibiotics (such as teicoplanin, through the ages One or two or more kinds in mycin), beta-lactam antibiotic (such as Amoxicillin), (such as ring third is husky for carbostyril antibiotic One or two or more kinds in star, Moxifloxacin), macrolide antibiotics (such as erythromycin) one or two or more kinds therein Drug.
- 4. sustained release pharmaceutical composition described in accordance with the claim 1, it is characterised in that：Described adhesive for ethyl alcohol, water, glycerine, .01-0.4mol/L one or more of acetic acid aqueous solution, volumetric concentration 0.1%-50% ethanol waters composition.
- 5. sustained release pharmaceutical composition described in accordance with the claim 1, it is characterised in that：The material of the coatings polymerize for lactic acid One or more of object, lactic acid-ethanol copolymer, chitosan composition.
- 6. according to the sustained release pharmaceutical composition described in claim 1 or 4, it is characterised in that：The molecular weight (Mw) of the chitosan： 5KD~500KD, deacetylation (DD%)：50~100%.
- 7. sustained release pharmaceutical composition described in accordance with the claim 1, it is characterised in that：The molecular weight (Mw) of the chitosan oligosaccharide：2KD ~3KD, deacetylation (DD%)：50~100%.
- 8. a kind of preparation method of any implant pellets of claim 1-7, it is characterised in that：1) medicated pellet is prepared using extrusion-spheronization：Antibiotic, carrier material, bonding agent composition are placed in extrusion Medicated pellet is made in extruded in spheronizator, round as a ball process；2) obtained medicated pellet is dried；3) coating material is dissolved in solvent and coating solution is made；Using fluidized bed coating equipment, it is micro- that coating solution is loaded on into drug containing Outside ball, the medicated pellet containing coatings is made.
- 9. according to preparation method according to any one of claims 8, it is characterised in that：The extrusion rotating speed of extrusion spheronization machine in the step 1) 10rpm~50rpm, round as a ball rotating speed 400rpm~2000rpm；Step 2) the drying means is one in spray drying, fluidized bed drying, vacuum drying, air dry oven drying means Kind.
- 10. according to preparation method according to any one of claims 8, it is characterised in that：Coating solution in the step 3), lactic acid polymer Solvent is one kind in acetone or dichloromethane or two kinds；The solvent of lactic acid-ethanol copolymer is in acetone or dichloromethane one Kind or two kinds；Chitosan solvent is one kind in water or acetic acid aqueous solution.
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| Application Number | Priority Date | Filing Date | Title |
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| CN201611096328.3A CN108143720A (en) | 2016-12-02 | 2016-12-02 | Anti-infectious sustained release pharmaceutical composition of biodegradation type hemostasis and preparation method thereof |
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| CN201611096328.3A CN108143720A (en) | 2016-12-02 | 2016-12-02 | Anti-infectious sustained release pharmaceutical composition of biodegradation type hemostasis and preparation method thereof |
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| CN (1) | CN108143720A (en) |
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