CN104434811A - Drug sustained-release microsphere capable of being embedded in intraocular lens loop and preparation method of drug sustained-release microsphere - Google Patents
Drug sustained-release microsphere capable of being embedded in intraocular lens loop and preparation method of drug sustained-release microsphere Download PDFInfo
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- CN104434811A CN104434811A CN201410624132.1A CN201410624132A CN104434811A CN 104434811 A CN104434811 A CN 104434811A CN 201410624132 A CN201410624132 A CN 201410624132A CN 104434811 A CN104434811 A CN 104434811A
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Abstract
The invention relates to a drug sustained-release microsphere capable of being embedded in intraocular lens loop and a preparation method of the drug sustained-release microsphere. The drug sustained-release microsphere prepared by the provided method can be used for effectively preventing and treating microorganism infection and antagonistic inflammatory reaction after a cataract surgery, reducing the occurrence rate of intraocular inflammation infection after the cataract surgery, and preventing and inhibiting after-cataract, so as to improve visual quality after the surgery. The technical scheme is that according to the drug sustained-release microsphere capable of being embedded in the intraocular lens loop, the drug sustained-release microsphere is formed by mixing drugs and a carrier at the ratio of 1 to (10000-1), and the drug sustained-release microsphere is 100-800mm in diameter. The preparation method of the drug sustained-release microsphere capable of being embedded in the intraocular lens loop sequentially comprises the following steps: (1) mixing the drugs and the carrier according to the ratio and stirring to obtain mixed liquid; (2) condensing fog-like materials in a collecting room to obtain microspheres; and (3) collecting the microspheres and screening the microspheres by virtue of a screen to obtain the microspheres with required diameters; disinfecting, sealing and packaging the microspheres.
Description
Technical field
The present invention relates to the medicament slow-release microsphere on a kind of foldable intraocular lens button loop be embedded in femtosecond laser cataract operation and phacoemulsification cataract surgery and preparation method, for suppressing, postcataract infected by microbes and antagonize inflammatory react, prevention and prohibition after cataract.
Background technology
Cataract is global primary blinding oculopathy; Surgical removal cataract implantable artificial crystalline lens treats the unique effective method of cataract at present.Cataract operation is quite ripe, but still existence may cause Postoperative visual acuity decline even to cause blind potential post-operative complication, as the infectious endophthalmitis, after cataract etc. of postcataract.Infectious endophthalmitis refers to retina, choroid and the Vitrea destructive inflammation reaction caused by microorganism, is one of the most serious complication of postcataract, and Du DT etc. report that its sickness rate is about 0.087%-0.327%.Although the sickness rate of this complication is not high, and along with the specification of sterile working and the application of medicine, its incidence rate, also in further reduction, because its poor prognosis, blind rate are high, is the focus that people pay close attention to all the time.The cause of disease of after cataract is the lens epithelial cell proliferation of postoperative residue, migration and epithelial-mesenchymal transdifferentiation cause Posterior capsular opacification, fibrosis and shrinkage, causes incident ray within the eye scattering occur and cause visual deterioration.About have the postcataract patient of 12.4-17.6% due to inverse position method row Nd-YAG laser operation, but there is certain complication in the operation of laser Posterior capsulotomy, as damaged intraocular lens in art, postoperative intraocular pressure rising, cystoid macular edema and detachment of retina etc., also can increase the medical burden of patient and society.Therefore, for complication such as the infectious endophthalmitis of postcataract and after cataract, we answer the various means of active adoption, reduce its incidence rate, improve the visual quality after operation in patients.
Research shows, the modal pathogen of infective endophthalmitis after cataract surgery is Grain-positive staphylococcus epidermidis (accounting for 30-80%) and staphylococcus aureus (accounting for 10-20%), in addition streptococcus (β Hemolytic streptococcus is also had, streptococcus pneumoniae, α Hemolytic streptococcus comprises light chain coccus and streptococcus salivarius, account for 10-35%), enterococcus (< 5%), gram-negative bacteria (comprises bacillus pyocyaneus, extremely rare, account for 5-20%), fungus (candidiasis, aspergillus, fusarium sp, account for 8%), multiple bacteriological infection (< 5%) etc., correct prevention and effective treatment are the keys of Perceived control metachromia endophthalmitis.Numerous researcher is by improving the attribute of intraocular lens own or introducing the incidence rate that anti-inflammatory substance reduces endophthalmitis.Hydrophobic intraocular implants's body front surface is modified as hydrophilic by phospholipid modified by Chinese patent CN1701769A " soft intraocular lens that phospholipid surface is modified and manufacture method thereof ", thus minimizing antibacterial and inflammatory cell are in the adhesion of intraocular lens, reduce inflammation incidence rate with this; Chinese patent CN1608601A " has the intraocular lens of catalytic coating " by artificial intraocular lenses's surface-coated photocatalytic material, excites and produce free radical through light, thus eliminates the microorganism of camera oculi anterior, prevention and prohibition endophthalmitis; Chinese patent CN103156708 A " button loop is inlaid with intraocular lens and the manufacture method thereof of medicament slow release microcapsule " by inlaying slow-releasing microcapsule on intraocular lens's button loop, and then reduce inflammation incidence rate, prevent and treat endophthalmitis, prevention after cataract.Although they, by improving surface nature or exciting anti-inflammatory agent around, to a certain degree suppress endophthalmitis,
Still there is following shortcoming: the scope 1) affected is only limitted to artificial intraocular lenses surface or near zone, and bacteriostasis is limited; 2) hydrophilic or free radical etc. to the inhibitory action of endophthalmitis and suppress degree uncertain, adjustability is not high.3) medicament slow release time and concentration there is no method and reach clinical practice requirement.For many years, numerous scholar is for suppressing after cataract, large quantity research is carried out to medicine and administering mode: such as Chinese patent CN101269240A " surface is with the manufacture method of the intraocular lens of anti-rotation grouth factor beta 2 antibody membrane ", by the method for LBL self-assembly, antibody deposition has been carried out original position to intraocular implants surface and suppress after cataract; Chinese patent CN101053680A " intraocular lens of the tool antiproliferative agents coating that control inverse position method is formed ", CN200973766Y " intraocular lens of control after cataract ", fix medicine respectively by outside coating or ambitus.Though said method suppresses by antibody iM situ or the medicine of local concentration suppresses residual proliferation of lens epithelial cells, can only be played a role by the antibody suppression of contact, the scope that can suppress is less; Or the medication coat poor stability formed, there is medicine and is coated with the probability released greatly, thus may to its hetero-organization toxic side effect of ophthalmic.
Summary of the invention
The object of the invention is the deficiency overcoming the existence of above-mentioned prior art, medicament slow-release microsphere providing a kind of intraocular lens of being embedded in fasten with a rope, string, etc. in hole and preparation method thereof; The medicament slow-release microsphere adopting the method to prepare effectively should be able to prevent and treat incidence rate, the prevention and prohibition after cataract of postcataract infected by microbes, antagonize inflammatory reaction, the infection of minimizing postcataract endophthalmitis disease, thus improves postoperative visual quality; The embedding of medicament slow-release microsphere simultaneously does not affect the stability of the aspect such as optics, mechanics of intraocular lens, has no side effect to eye inner tissues such as human cornea endothelium, ciliary epithelium cell, iris, choroid and retinas; The manufacture method provided is simple ripe practical, the cost of raw material is low and can industrial mass production.
Technical scheme provided by the invention is:
Be embedded in the medicament slow-release microsphere on intraocular lens's button loop, it is characterized in that described medicament slow-release microsphere is mixed to form in the ratio of 1:10000-1 by medicine and carrier, diameter is 100-800 micron.
Described step 1) in carrier, for conventional medical excipient, as any one in glyceryl tristearate, glyceryl monostearate, stearic acid, Glyceryl Behenate, three certain herbaceous plants with big flowers acid glycerides, trilauryl glyceride, myristin and tripalmitin.
Described step 1) in medicine be the medicine of control postcataract infected by microbes, antagonize inflammatory reaction, comprise all kinds of antibiotic, steroidal anti-inflammatory medicine and NSAID (non-steroidal anti-inflammatory drug); Or the medicine of prevention and prohibition after cataract, comprise medicine, cell death inducing medicine that antimetabolitas and mitotic inhibitor, the medicine of inflammation-inhibiting reaction, immunotoxin and cytotoxin, T suppression cell and extracellular matrix stick.
Be embedded in a preparation method for the medicament slow-release microsphere on intraocular lens's button loop, comprise the following steps successively:
1) mixed with the ratio of carrier in 1:10000-1 by medicine, 75-100 DEG C of water-bath is also constantly uniformly mixed, and obtains mixing material until dissolve;
2) by the compressed air of 0.1-14kpa by pipeline transport to through heating shower nozzle, then spray from the nozzle of shower nozzle; The temperature of heating shower nozzle is 80-100 DEG C, and the diameter of nozzle is 100-1500 micron;
Meanwhile, with the speed of 0.1-5ml/sec by step 1) mixing material that obtains is injected in shower nozzle, and companion compressed air forms spray from nozzle ejection together, makes spray be condensed into microsphere at collecting chamber;
3) collect step 3) described in microsphere, obtain the microsphere of required diameter through screen cloth choosing, and through sterilization, pack.
Described step 2) in collecting chamber be confined space or opening container.
Described step 3) microsphere diameter that obtains is 100-800 micron.
Described step 3) in sterilization adopt oxirane.
Beneficial effect of the present invention: 1) medicament slow-release microsphere provided by the invention is in company with after IOP implantation ophthalmic pouch, continued smooth is discharged entrained medicine, effectively can suppress ophthalmic microorganism, antagonize inflammatory reaction, targeted inhibition lens epithelial cells, reduce the incidence rate of the infection of postcataract endophthalmitis disease, inflammatory reaction and after cataract, thus improve postoperative visual quality and Long-term visual outcome; And the medicine discharged steadily is between valid density and toxic and side effects concentration, do not affect its hetero-organization of ophthalmic; 2) because the composition forming drug sustained release system is the matrix material that biocompatibility is good, there is hypotoxicity and immunogenicity, therefore intraocular lens provided by the invention respectively organizes almost non-toxic side effect to ophthalmic such as human cornea endothelium, ciliary epithelium cell, iris, choroid and retinas, has good biocompatibility.3) the present invention is by comparatively simple melting--spraying--condensation process, inlays suitable size, Nantural non-toxic, constitutionally stable medicament slow-release microsphere on intraocular lens fastens with a rope, string, etc. hole.4) manufacture method of the present invention by change the kind of excipient, medicine and excipient ratio, add as modes such as emulsifying agent such as oleic acid, simple and effective adjustment is carried out to the drug loading of medicament slow-release microsphere and rate of release, namely the slow-release capability of regulating drug sustained-release micro-spheres is come to the medicine of different molecular weight, different release request such as the standards such as time length, and by the surface topography to medicine carrying microballoons such as scanning electron microscope, the embedding year microsphere situation on artificial intraocular lenses surface carries out observation evaluation, carries out visible, autotelic adjustment; 5) manufacture method of the present invention is without the need to using solvent, environmentally friendly, specifically avoid in large-scale commercial process the pollution that environment may cause; The medicine range of choices loaded is wide, as long as the medicine of stable in properties all can adopt at the working temperature; 6) manufacturing process of the present invention is simple, easy, and more any technique all more saved time, and the instrument price of required dependence is cheap, be easy to obtain and promote; The cost of material adopted is low, and being therefore applicable to very much becomes the industrialization product that a kind of performance is desirable, cheap, can be mass-produced.
Accompanying drawing explanation
Fig. 1-1 to Fig. 1-2 is photo figure in kind of the present invention; Wherein Fig. 1-1 is the light microscopic photo of Chinese medicine sustained-release micro-spheres of the present invention, and Fig. 1-2 is the intraocular lens's structural representation being embedded with medicament slow-release microsphere in button loop hole of the present invention.
Fig. 2-1 is scanning electron microscope (SEM) form on Chinese medicine sustained-release micro-spheres surface of the present invention.Fig. 2-2 is embedded in intraocular lens to fasten with a rope, string, etc. the scanning electron microscope form on medicament slow-release microsphere surface in hole.
Fig. 3 is the structural representation of medicament slow-release microsphere preparation facilities involved by embodiment.
Fig. 4-1 to 4-2 is embedded in intraocular lens to fasten with a rope, string, etc. the medicament slow release result of hole medicament slow-release microsphere; Wherein Fig. 4-1 is that each time point is embedded in intraocular lens and fastens with a rope, string, etc. the drug level that hole medicament slow-release microsphere discharges in PBS, and Fig. 4-2 is that each time point is embedded in intraocular lens and fastens with a rope, string, etc. the percent of drug of hole medicament slow-release microsphere cumulative release in PBS.
Fig. 5-1 to 5-2 is the fluorescence photo of different intraocular lens's bacteriostasis contrast; Wherein Fig. 5-1 is the common artificial lenticular bacteriostasis not inlaying medicament slow-release microsphere, and point W is wherein dead staphylococcus epidermidis, and all the other points are the staphylococcus epidermidis of survival; Fig. 5-2 is the bacteriostasis in the present invention, button loop being embedded with medicament slow-release microsphere intraocular lens, and point F is wherein the staphylococcus epidermidis of survival, and all the other points are dead staphylococcus epidermidis.All insert in staphylococcus epidermidis bacterium liquid and cultivate after 24 hours, use Live/Dead test kit to carry out fluoroscopic examination, and then judge intraocular lens of the present invention in vitro to the staphylococcic rejection ability of epidermis.
Fig. 6-1 to 6-2 is the result of x-ray photoelectron spectroscopy analysis (XPS) detection of drugs sustained-release micro-spheres and the elementary composition change of intraocular lens's surface chemistry being embedded with medicament slow-release microsphere; Wherein 6-1 is that medicament slow-release microsphere surface chemistry element is formed and ratio analysis result, and 6-2 is formed and ratio analysis result for button loop being embedded with medicament slow-release microsphere intraocular lens surface chemistry element.
Fig. 7 is the spectral transmittance result being embedded with medicament slow-release microsphere intraocular lens in the present invention.
detailed description of the invention
The structure of intraocular lens 1 of the present invention is as described in Fig. 1-2: the both sides of optic 1-1 are shaped with a button loop 2 respectively, button loop on or to fasten with a rope, string, etc. and the connecting portion of optic is drilled with several holes 3 of fastening with a rope, string, etc., is inlaid with medicament slow-release microsphere in hole of fastening with a rope, string, etc.Above-mentioned intraocular lens has applied for Chinese patent (application number 201310042582.5).
The material of described intraocular lens is polymethyl methacrylate, hydrophobic polyacrylate or Silica hydrogel.
The manufacture method of this medicament slow-release microsphere, carry out (see Fig. 3) successively according to following steps:
1) by medicine and carrier by a certain percentage (preferred proportion is 1:10000-1) mix, 75-100 DEG C of water-bath also constantly stirs the mixture until be dissolved into mixing material, is then injected into the speed of 0.1-5ml/sec (nozzle diameter of shower nozzle is 100-1500 micron) in the shower nozzle being heated to 80-100 DEG C; The compressed air (recommending air compressor to produce) of 0.1-14kpa is transported in shower nozzle by pipeline simultaneously, from nozzle ejection (keeping certain spraying altitude, from collecting chamber bottom surface or at least 1 meter, accepter bottom surface height) together with mixing material; Aforesaid liquid namely in the air of opening container (unlimited receptor) or confined space (convenient collect) spray congealing be the microsphere of 100-800 micron, after collection through oxirane disinfection, pack.
Keep certain spraying altitude, object has certain condensation time in atmosphere before the fog-like liquid making to spray in nozzle falls earthward, thus obtain the higher microsphere of circularity.
The heating means of described shower nozzle, recommend to adopt electric heater heating or far-infrared heater (alcohol burner also can be adopted to heat).
2) medicament slow-release microsphere embedded button loop hole can be through hole, or blind hole; Medicament slow-release microsphere is embedded in the position on intraocular lens's button loop, can from optic edge and the optional position of button loop intersection to the tip of fastening with a rope, string, etc.; Any length in inside of button loop and the hollow tubular cavity of diameter can also be embedded in.
Carrier of the present invention, for conventional solid lipid material, as glyceryl tristearate, glyceryl monostearate, stearic acid, Glyceryl Behenate, three certain herbaceous plants with big flowers acid glycerides, trilauryl glyceride, myristin, tripalmitin etc.; One wherein can be selected during use.
Medicine of the present invention suppresses postcataract infected by microbes and antagonize inflammatory reaction, all ophthalmology common medicines of prevention and prohibition after cataract and new drug.Postcataract infected by microbes and antagonize inflammatory reaction is suppressed to comprise: antibiotic and anti-inflammatory agent, the former can directly or indirectly kill or suppress microorganism, of a great variety, comprise beta-lactam antibiotic, fluoroquinolone antibiotics, macrolide antibiotics, aminoglycoside antibiotics, Tetracyclines, rifomycins, polymyxin B, fusidic acid, chloromycetin, vancomycin etc.; The latter's anti-inflammatory agent comprises steroidal anti-inflammatory drugs and nonsteroidal antiinflammatory drug, steroidal anti-inflammatory drugs mainly corticoid, antiphlogistic effects is good, but life-time service can cause water-electrolyte metabolism and disorder that is sugared, fatty, protein metabolism, NSAID (non-steroidal anti-inflammatory drug) is of a great variety, all by suppressing the activity of Cycloxygenase, suppress arachidonic acid, stop synthesis and the release of prostaglandin, thus stop the inflammatory mediator such as thromboxane and Kallidin I to play antiinflammatory action, comprise ethylene salicylic acid salt, non-ethylene salicylic acid salt, non-salicylic acid salt.If suppress the drug main of the after cataract of complications after cataract extraction by suppressing the residual proliferation of lens epithelial cells of postcataract, dividing a word with a hyphen at the end of a line in Lens capsular, or be converted into fibroblast etc. and play the effect suppressing after cataract, it mainly comprises the medicine, cell death inducing medicine etc. of antimetabolitas and mitotic inhibitor, the medicine of inflammation-inhibiting reaction, immunotoxin and cytotoxin, T suppression cell and extracellular matrix adhesion.
Concrete medicine is in table 1 (can select the mixing of one or more arbitrary proportions wherein) during use:
Embodiment 1:
The manufacture method of medicament slow-release microsphere comprises the following steps:
1) Gatifloxacin powder 500mg and glyceryl tristearate powder 1500mg is placed in glass beaker, beaker heats and stirs in 80 DEG C of water-baths, until solid melting; Extract 5ml aforesaid liquid with syringe and be injected into rapidly (jet diameters is 1500 microns) in the shower nozzle being heated to 80 DEG C with the speed of 1ml/sec; The air of the 6.8kpa simultaneously exported from air compressor by spraying (about spraying altitude 1.0m) from the nozzle of shower nozzle together with aforementioned liquids again after heating shower nozzle, aforesaid liquid namely in atmosphere spray congealing be the microsphere of 400-800 micron; Ethane via epoxyethane is sterilized, is packed.
Example 2:
1) fleroxacin powder 300mg and stearic acid powder 700mg is placed in glass beaker, beaker heats and stirs in 75 DEG C of water-baths, until solid melting; Extract 3ml aforesaid liquid with syringe and be injected into rapidly (jet diameters is 1000 microns) in the shower nozzle being heated to 75 DEG C with the speed of 0.5ml/sec; The air of the 7.1kpa simultaneously exported from air compressor by spraying (about spraying altitude 1.5m) from the nozzle of shower nozzle together with aforementioned liquids again after heating shower nozzle, aforesaid liquid namely in atmosphere spray congealing be the microsphere of 600 microns; Ethane via epoxyethane is sterilized, is packed.
Example 3:
1) clarithromycin powder 400mg, oleic acid 200mg and monoglyceride powder 400mg are placed in glass beaker, beaker heats and stirs in 70 DEG C of water-baths, until solid melting; Extract 2ml aforesaid liquid with syringe and be injected into rapidly (jet diameters is 600 microns) in the shower nozzle being heated to 70 DEG C with the speed of 1.5ml/sec; The air of the 5.5kpa simultaneously exported from air compressor is by after heating shower nozzle, be ejected to (about spraying altitude 2.0m) in confined space from the nozzle of shower nozzle again together with aforementioned liquids, aforesaid liquid namely in atmosphere spray congealing be the microsphere of 200 microns; Ethane via epoxyethane is sterilized, is packed.
The heating of shower nozzle in above-mentioned 3 embodiments, can adopt electric heater or far-infrared heater or alcohol burner.
The present invention has also made following mensuration to the medicament slow-release microsphere being embedded in intraocular lens prepared in above-mentioned example:
Get the intraocular lens untreated intraocular lens and button loop being embedded with medicament slow-release microsphere, observe the configuration of surface of IOL after surface spray platinum with SEM, accelerating potential during test is 25kV, and enlargement ratio is 100 times; As Figure 1-1.Fig. 2-1 is scanning electron microscope (SEM) form on Chinese medicine sustained-release micro-spheres surface of the present invention, and microsphere is closely knit, surface slightly gauffer and small hole; Fig. 2-2 is that the intraocular lens being embedded with medicament slow-release microsphere fastens with a rope, string, etc. the scanning electron microscope form on surface, and button loop hole circle, edge is slightly crude, and medicament slow-release microsphere is fixed in button loop hole, and surface topography is not damaged in the process of suction button loop hole.The slow-release capability of the medicament slow-release microsphere that the above-mentioned the present invention of being all is embedded on intraocular lens's button loop provides physical basis.
Get the intraocular lens 3 pieces button loop being embedded with medicament slow-release microsphere, be placed in 1mlPBS 37 DEG C of waters bath with thermostatic control respectively, 100r/m shakes, change liquid respectively in 1mlPBS in 15min, 30min, 45min, 60min, 120min, 180min, 1-7d, 12d, 17d, 22d, 27d, 32d, high efficiency liquid phase chromatographic analysis method measures the release amount of medicine in each time point PBS.Fig. 4-1 to 4-2 is the medicament slow release result of the medicament slow-release microsphere be embedded on intraocular lens's button loop.Fig. 4-1 is the drug level that each time point is embedded in the medicament slow-release microsphere on intraocular lens's button loop and discharges in PBS; Fig. 4-2 is percent of drug that each time point is embedded in the medicament slow-release microsphere cumulative release in PBS on intraocular lens's button loop.
After the monoclonal of ATCC12228 S. epdermidis strains is hatched 24 hours on 37 DEG C of constant-temperature tables, get 1ml bacterium liquid respectively and be placed in 24 orifice plates, add the intraocular lens untreated intraocular lens and button loop being embedded with medicament slow-release microsphere respectively, cultivating in 37 DEG C of incubators after 24 hours uses Live/Dead test kit to carry out fluoroscopic examination, compares two kinds of artificial lenticular bacteriostasis of difference.Wherein Fig. 5-1 is the common artificial lenticular bacteriostasis of not embedding medicament slow-release microsphere, and point W is wherein dead staphylococcus epidermidis, and all the other points are the staphylococcus epidermidis of survival; Fig. 5-2 is the bacteriostasis in the present invention, button loop being embedded with the intraocular lens of antibiotic medicine sustained-release micro-spheres, and point F is wherein the staphylococcus epidermidis of survival, and all the other points are dead staphylococcus epidermidis; Visible medicament slow-release microsphere has good In Vitro Bacteriostasis ability.
Get medicament slow-release microsphere and the upper embedding intraocular lens being loaded with medicament slow-release microsphere of button loop, employing condition is aluminum/magnesium target, high pressure 14.0kV, power 250W, vacuum is better than the x-ray photoelectron spectroscopy analysis (XPS) of 1 × 10-8 Torr, detection of drugs sustained-release micro-spheres and the elementary composition result of variations of surface chemistry being embedded with medicament slow-release microsphere intraocular lens.Wherein 6-1 is that medicament slow-release microsphere surface chemistry element is formed and ratio analysis result; 6-2 is formed and ratio analysis result for being embedded with medicament slow-release microsphere intraocular lens surface chemistry element.
Medical apparatus and instruments inspection institute of Zhejiang Province application CFDA is entrusted to carry out focal power, picture element, spectral transmittance and dynamic fatigue durability test about the national standard (YY-0290) of IOL quality testing to intraocular lens button loop being embedded with medicament slow-release microsphere.Focal power button loop being embedded with the intraocular lens (20D) of medicament slow-release microsphere, between franchise ± 0.4D, meets national standard; The intraocular lens (20D) button loop being embedded with medicament slow-release microsphere is more than or equal to 0.43 in modulation transfer function (MTF) (MTF) value of schematic eye system at spatial frequency 100mm-1 place, meets national standard; When the intraocular lens (20D) button loop being embedded with medicament slow-release microsphere is using the wavelength of spectral transmittance 10% correspondence as UV cutoff wavelength, this wavelength should be not less than 360nm, and 360nm is less with the spectral transmittance down to 300nm section, meets national standard; All buttons loop can bear that compression distance scope amplitude is ± 0.25nm, the near sinusoidal in 250000 cycles distortion and without fracture, meet national standard.Fig. 7 is the spectral transmittance result in the present invention, button loop being embedded with the intraocular lens of medicament slow-release microsphere.
Conclusion: medicament slow-release microsphere provided by the invention is embedded in intraocular lens and fastens with a rope, string, etc. after hole implants human eye pouch, the medicine of sustainable steady release valid density, and effective duration can be maintained, thus inhibitory action is produced to inflammation or after cataract, neither affect the mechanics of intraocular lens, optical characteristics, also can not produce toxic and side effects to eye inner tissue, be conducive to the visual effect of long-term postoperative, reduce operation risk.
Claims (6)
1. can be embedded in the medicament slow-release microsphere on intraocular lens's button loop, it is characterized in that described medicament slow-release microsphere is mixed to form in the ratio of 1:10000-1 by medicine and carrier, diameter is 100-800 micron.
2. the medicament slow-release microsphere be embedded on intraocular lens's button loop according to claim 1, it is characterized in that: described step 1) in carrier be conventional medical excipient, any one namely in glyceryl tristearate, glyceryl monostearate, stearic acid, Glyceryl Behenate, three certain herbaceous plants with big flowers acid glycerides, trilauryl glyceride, myristin and tripalmitin.
3. the medicament slow-release microsphere be embedded on intraocular lens's button loop according to claim 2, it is characterized in that: described step 1) in medicine be the medicine of control postcataract infected by microbes, antagonize inflammatory reaction, be all kinds of antibiotic, steroidal anti-inflammatory medicine and NSAID (non-steroidal anti-inflammatory drug); Or the medicine of prevention and prohibition after cataract, comprise medicine, cell death inducing medicine that antimetabolitas and mitotic inhibitor, the medicine of inflammation-inhibiting reaction, immunotoxin and cytotoxin, T suppression cell and extracellular matrix stick.
4. the preparation method of the medicament slow-release microsphere be embedded on intraocular lens's button loop according to claim 1, comprises the following steps successively:
1) mixed with the ratio of carrier in 1:10000-1 by medicine, 75-100 DEG C of water-bath is also constantly uniformly mixed, and obtains mixing material until dissolve;
2) by the compressed air of 0.1-14kpa by pipeline transport to through heating shower nozzle, then spray from the nozzle of shower nozzle; The temperature of heating shower nozzle is 80-100 DEG C, and the diameter of nozzle is 100-1500 micron;
Meanwhile, with the speed of 0.1-5ml/sec by step 1) mixing material that obtains is injected in shower nozzle, and companion compressed air forms spray from nozzle ejection together, makes spray be condensed into microsphere at collecting chamber;
3) collect step 3) described in microsphere, obtain the microsphere of required diameter through screen cloth choosing, and through sterilization, pack.
5. the preparation method of the medicament slow-release microsphere be embedded on intraocular lens's button loop according to claim 4, is characterized in that: described step 2) in collecting chamber be opening container or confined space.
6. the preparation method of the medicament slow-release microsphere be embedded on intraocular lens's button loop according to claim 5, is characterized in that: described step 3) in sterilization adopt oxirane.
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| CN105476730A (en) * | 2016-01-06 | 2016-04-13 | 中国医科大学附属第四医院 | Medicine nanometer lipid carrier and artificial lens system and application thereof |
| EP3210572A1 (en) | 2016-02-29 | 2017-08-30 | Elodie Jane Siney | Intraocular lens comprising drug-containing microspheres |
| CN112402098A (en) * | 2020-11-19 | 2021-02-26 | 浙江大学 | Drug-eluting intraocular lens with slow release function and preparation method thereof |
| CN113018508A (en) * | 2021-03-15 | 2021-06-25 | 西安交通大学医学院第一附属医院 | Surface-modified artificial lens and preparation method thereof |
| CN114377627A (en) * | 2022-01-13 | 2022-04-22 | 哈尔滨工业大学 | Method for preparing artificial cells containing onion-shaped multilayer phospholipid membrane structure by one-step temperature control method |
| CN114618019A (en) * | 2020-12-11 | 2022-06-14 | 苏州北科纳米科技有限公司 | Preparation method of artificial lens material for preventing infectious endophthalmitis |
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