CN101683538B - Lacrimal passage stopper and preparation method thereof - Google Patents
Lacrimal passage stopper and preparation method thereof Download PDFInfo
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- CN101683538B CN101683538B CN 200810200755 CN200810200755A CN101683538B CN 101683538 B CN101683538 B CN 101683538B CN 200810200755 CN200810200755 CN 200810200755 CN 200810200755 A CN200810200755 A CN 200810200755A CN 101683538 B CN101683538 B CN 101683538B
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Abstract
本发明提供一种泪道塞，系由聚乙烯醇和聚乙烯吡咯烷酮以1：3—3：1的重量比制成的棒状物，所述聚乙烯醇的分子量为20,000～200,000，所述聚乙烯吡咯烷酮的分子量为8,000—200,000。本发明泪道塞的制备方法包括以下步骤：将原料溶于80℃以上热水中，冷却至70℃，灌至模具；在烘箱中60℃烘20min；过夜冷却，脱模成型。本发明的泪道塞经毒理试验和动物模型试验证实，具有安全性和良好的生物相容性，可明显改善干眼症状，具有临床实用性。其制作工艺简单，成本较低，符合我国经济水平，有利于今后开发、应用。The invention provides a lacrimal plug, which is a rod made of polyvinyl alcohol and polyvinylpyrrolidone at a weight ratio of 1:3-3:1, the molecular weight of the polyvinyl alcohol is 20,000-200,000, and the polyethylene The molecular weight of pyrrolidone is 8,000-200,000. The preparation method of the lacrimal duct plug of the present invention comprises the following steps: dissolving raw materials in hot water above 80°C, cooling to 70°C, pouring into a mold; drying in an oven at 60°C for 20 minutes; cooling overnight, and demoulding. The lacrimal duct plug of the invention has been proved by toxicological tests and animal model tests, has safety and good biocompatibility, can obviously improve dry eye symptoms, and has clinical practicability. Its manufacturing process is simple, the cost is low, it is in line with the economic level of our country, and it is beneficial to development and application in the future.
Description
Technical field
The invention belongs to the medical devices field, specifically, the present invention relates to the ophtalmic treatments equipment, relate more specifically to a kind of lacrimal passage stopper.
Background technology
Xerophthalmia is the unstable and eye table organization damage of the tear film that unusually causes of a kind of tear quality and quantity or kinetics and with the eye surface diseases take the ophthalmic uncomfortable symptom as feature.Along with the change of people life style and popularizing of computer, morbidity of dry eye is the trend that rises year by year, and proportion constantly increases in the ophthalmology the rate of receiving out-patient clinic service.According to incompletely statistics, the morbidity of dry eye of China is between 7%～10%.
Traditional dry eye treatment method is take artificial tears's eye drip as main, and 17-hydroxy-11-dehydrocorticosterone, immunosuppressant and lacrimal passage stopper also are used to the treatment of xerophthalmia.Make and be aided with the xerophthalmia symptom that the lacrimal passage stopper treatment can effectively improve patients with dry eye when healing with medicine.But because concrete technology and patent protection, import lacrimal passage stopper expensive by the income level of population of China is difficult to bear, still can not be used widely, and can not fundamentally reach the purpose of improvement crowd dry eye symptoms and sign.At present domesticly not yet develop and develop relevant lacrimal passage stopper and treat xerophthalmia and relevant disease, therefore necessary on the basis of reference advanced foreign technology, a kind of lacrimal passage stopper of suitable China's national situation is developed in independent development, finally improves the sings and symptoms of crowd's xerophthalmia.
Therefore, the object of the present invention is to provide a kind of lacrimal passage stopper safe, effective, with low cost and preparation method thereof.
Summary of the invention
Lacrimal passage stopper provided by the invention is the club of being made with the weight ratio of 1:3-3:1 by polyvinyl alcohol and polyvinylpyrrolidone, and the molecular weight of described polyvinyl alcohol is 20,000～200,000, the molecular weight of described polyvinylpyrrolidone is 8,000-200,000.
The pure and mild polyvinylpyrrolidone of material polyethylene of preparation lacrimal passage stopper of the present invention is take medical grade as good.
Lacrimal passage stopper of the present invention length under drying regime is generally 6-11mm, and radius is generally 0.2-0.6mm.The large I of lacrimal passage stopper designs according to the people (adult, old people or child) who uses this lacrimal passage stopper or the lacrimal passage size of animal.For example, in general, human lacrimal passage stopper length under drying regime is 10 ± 1mm, and radius is 0.3 ± 0.1mm; Rabbit is 8 ± 2mm with lacrimal passage stopper length under drying regime, and radius is 0.5 ± 0.1mm.
Lacrimal passage stopper preparation method provided by the invention may further comprise the steps:
(1) polyvinyl alcohol and the polyvinylpyrrolidone ratio with 1:3-3:1 is dissolved in 80-95 ℃ of hot water, is cooled to 70 ℃, fill with to mould;
(2) 60 ℃ of baking 20min in baking oven, the cooling of spending the night, stripping forming makes lacrimal passage stopper.
Use medical grade polyvinyl alcohol and polyvinylpyrrolidone in the preferred embodiment of the inventive method.
In the preferred embodiment of the inventive method, the lacrimal passage stopper that makes can be soaked 2h in 50% ethanol and carry out purification process.
In the preferred embodiment of the inventive method, the lacrimal passage stopper that ethanol purification is processed can be soaked 24h again in distilled water.
In the preferred embodiment of the inventive method, can with the lacrimal passage stopper processed through ethanol purification and distilled water immersion in thermostatic drying chamber in 50-60 ℃ of baking 1-3 hour.
In the preferred embodiment of the inventive method, the lacrimal passage stopper of oven dry can be carried out sterilization treatment.
Lacrimal passage stopper of the present invention confirms to have safety and good biocompatibility through toxicological test and animal model test, can obviously improve the xerophthalmia symptom, has Clinical practicability.Its processing technology is simple, and cost is lower, meets China's economic level, is conducive to Future Development, application.
Description of drawings
Fig. 1 represents the lacrimal passage stopper under the drying regime.
Fig. 2 A lacrimal passage stopper behind the 24h that represents to soak; Fig. 2 B represent to soak transverse diameter of lacrimal passage stopper behind the 24h.
Fig. 3 A, 3B are respectively the light microscopy checking result of matched group (H.E * 10) and the subcutaneous implant site of test group (H.E * 10).
Fig. 4 A, 4B are respectively the light microscopy result of matched group B4 (H.E * 10) and test group E3 (H.E * 40) (inserting after two months) cornea.
Fig. 5 A, 5B are respectively the light microscopy result of matched group D3 (H.E * 10) and test group E4 (H.E * 10) lacrimal passage surrounding tissue.
Fig. 6 A, 6B are respectively the light microscopy result of matched group C5 (H.E * 10) and test group E2 (H.E * 20) (inserting after two months) conjunctival tissue.
Fig. 7 A, 7B are respectively the electron microscopic examination result of matched group D3 (* 1500) and test group E4 (* 2000) cornea specimen.
Fig. 8 A, 8B be respectively ATD group insert before the lacrimal passage stopper and insert lacrimal passage stopper after 40 days conjunctiva impression cytology check result.
The specific embodiment
Below for a more detailed description to the present invention with embodiment and test example.They only are the descriptions to best mode for carrying out the invention, scope of the present invention are not consisted of any restriction.
Embodiment 1
(1) polyvinyl alcohol and the polyvinylpyrrolidone ratio with 1:1 is dissolved in 80 ℃ of water, is cooled to 70 ℃, fill with to mould;
(2) 60 ℃ of lower baking 20min in baking oven, the cooling of spending the night, stripping forming;
(3) in 50% ethanol, soak 2h and carry out purification process;
(4) in distilled water, soak again 24h;
(5) put into 60 ℃ of lower baking 1h of thermostatic drying chamber; With
(6) pack in the aseptic vial.
With two kinds of moulds, make the lacrimal passage stopper of two kinds of sizes.Wherein a kind of under drying regime length be 10 ± 1mm, radius is 0.3 ± 0.1mm; Another kind length under drying regime is 8 ± 2mm, and radius is 0.5 ± 0.1mm.
The lacrimal passage stopper of the second size is immersed in the distilled water under room temperature, and length is 11 ± 0.2mm after 24 hours, and radius is 2.2 ± 0.3mm.
This lacrimal passage stopper is in 38 ℃ of long-time immersions, degradable in the time of 62 ± 4 days.
Embodiment 2
Except polyvinyl alcohol and the polyvinylpyrrolidone ratio with 1:3 is dissolved in 90 ℃ of water, all the other make lacrimal passage stopper equally with embodiment 1.
Embodiment 3
Except polyvinyl alcohol and the polyvinylpyrrolidone ratio with 3:1 is dissolved in 85 ℃ of water, all the other make lacrimal passage stopper equally with embodiment 1.
Test example
Laboratory animal: New Zealand white rabbit, male and female are not limit, body weight 2～3kg, available from Tongji University's Experimental Animal Center, credit number SYXK (Shanghai) 2002-0038; Cavia porcellus, male and female are not limit, and body weight 200～350g at the 1-2 monthly age, is provided by zoopery center, Chinese Academy of Sciences Shanghai.
Test example 1 biocompatibility test
1. cell toxicity test
In this test, test group is lacrimal passage stopper of the present invention (clean with suds, distilled water washs, and filter paper blots, high pressure steam sterilization 20min); Positive controls is 64g/L phenol solution (1ml), and negative control group is the blank tube that contains the medical stainless steel silk.
The dislocation of cervical vertebra method is put to death mice, and the eyeball blood-letting is immersed Mus in 75% ethanol and to be moved into sterilizing room; Put into porcelain dish, use 75% ethanol disinfection; Cut off skin taking-up partial skin tissue and put into the plate that contains PBS liquid; With medical scissors tissue is cut into the 1.5-2.0mm fritter, with adding 0.25% trypsin after the PBS washing and transferring in the little triangular flask, 37 ℃ of digestion 20min abandon supernatant; With 0.25% trypsinization piece of tissue 3 times, each 7-10min abandons supernatant.The precipitation part is l cell, and going down to posterity to grow through 48-72h obtains vigorous cell, is for experiment.
With the DMEM/F12 cell culture medium above-mentioned l cell is prepared 4 * 10
4Individual/ml cell suspension, dispensing is (1ml/ pipe) in vitro, test group 10 pipes (1 pipe is for subsequent use), and positive controls 3 pipes, negative control group 13 pipes (1 pipe is for subsequent use) are put in 37 ℃ of constant incubators and are cultivated 24h.Cell culture medium is pressed 1cm
2The ratio adding of lacrimal passage stopper surface area 10ml is placed with in the test tube of sample lixiviate 24h under 37 ℃ of constant temperature.Behind the 24h, every pipe is given up original fluid, and test group, negative control group pipe change to fresh medium, and positive controls changes to the cell culture fluid that contains 64g/L phenol, and manage the negative control pipes to 3 and carry out cell counting as the blank group, all the other are put 37 ℃ and continue to cultivate.
Respectively at 2,4,7 days matched group and test group are respectively got 3 pipes, carry out absorbance measurement with spectrophotometer, to judge the propagation degree of cell.
Assay method: discard the archeocyte culture fluid, with the PBS washing, 10% formalin is 10min fixedly, wash 3 times, add 5g/L crystal violet rowland 1.5ml dyeing 3min, wash 3 times, add 10g/L sodium lauryl sulphate 3.5ml, under wavelength 588nm, measure absorbance with spectrophotometer.
Computing formula: RGR (%)=(test group absorbance-blank group absorbance)/(positive controls absorbance-blank group absorbance) * 100.
Convert the RGR value to behind six order reactions evaluation material toxic action by standard, the results are shown in Table 1.
Toxicity grading table of different observation stage of table 1
| Minute | Absorbance (mean+SD) | Relative propagation degree (%) | Toxicity grading |
| 2 days | Matched group 0.7835 ± 0.06 test group 0.791 ± 0.05 | 101 | 0 grade |
| 4 days | Matched group 1.34 ± 0.08 test group 1.43 ± 0.03 | 106 | 0 grade |
| 7 days | Matched group 1.4327 ± 0.03 test group 1.4297 ± 0.04 | 99 | 1 grade |
Because each time limit cytotoxicity evaluation of test group is all in the 0-1 level, therefore think that the cell toxicity test of lacrimal passage stopper material of the present invention is qualified.
2. sensitization test (STT)
Select healthy guinea pig, be divided into test group, positive group, negative group, every group each 5,24h before the test shaves except guinea pig back 4 * 6cm
2The zone hair.
Normal saline is the lixiviate medium, produces lacrimal passage stopper material lixiviating solution.Positive control is 5% formalin, and negative control is normal saline.After prerun, if the test(ing) liquid ultimate density causes local ulcer, necrosis or general reaction then concentration to be reduced to maximum tolerated dose.
70% ethanol cleaning Cavia porcellus unhairing district, every Cavia porcellus ridge both sides 6 point symmetry intradermal injections, each point is at a distance of 1-1.5cm, and every some injection volume is 0.1ml.Intradermal injection is after 1 week, hair is shaved in the district once again in the Cavia porcellus unhairing, 70% ethanol cleaning, as do not produce irritation, each injection site sticks behind the 24h in lixiviating solution or negative and positive contrast liquid and is dipped to 2 saturated * 4cm with 100g/L sodium lauryl sulphate paraffin liquid (SLS) coating
2Filter paper, fixing and indwelling 48h ± 2h.Behind the local patch 14d, with Cavia porcellus abdominal part one side hair cutting, clean with 70% ethanol, stick the filter paper with above-mentioned disposal in abdominal part unhairing district, fixing and indwelling 24h ± 1h.Remove to stick to observe behind thing 24h, 48h, the 72h and excite the position reaction, excite position erythema and edema reaction classification, evaluation sensitivity response situation by each observing time of standard recording and each.
Found that, the test group day part each excite the position all without the reaction of erythema and edema, is assessed as 0 grade of dermoreaction, thinks this test sample sensitization of skin pass the test.
3. pyrogen testing
New Zealand white rabbit is under same environmental condition, raise, observed for 1 week with same feedstuff, the rabbit body weight does not alleviate, spirit, appetite, drainage are without unusually, carry out prescreen, namely every 1h take temperature 1 time, survey altogether 4 times, body temperature is all in 38.0-39.6 ℃ of scope, and the highest and minimum body temperature is poor, and to be no more than 0.4 ℃ rabbit selected.
Adopting 0.9% sodium chloride injection of prerun nonpyrogenic is the lixiviate medium, produces lacrimal passage stopper material lixiviating solution of the present invention.All utensils that contact with lixiviating solution all should place in the electrically heated drying cabinet, do roasting 2h Pyrogen Removing for 180 ℃.
Tested front 2 days, and should be in the same environment for rabbit on probation, laboratory and the receptacle temperature difference are not more than 5 ℃, and in the single test process, the room temperature variation is not more than 5 ℃.The material lixiviating solution is done preliminary examination with 3 rabbits, carries out retrial with 5 rabbits again.Prediction body temperature 3 times behind the rabbit fasting 2h, blanking time 30min, rear twice body temperature is poor to be no more than 0.2 ℃, with the normal body temperature of this twice body temperature meansigma methods as this rabbit.Use rabbit body temperature should be in 38.0-39.6 ℃ of scope, and normal body temperature is no more than 1 ℃ between each rabbit.For avoiding restless, rabbit is placed in the holder, beginning thermometric for the first time inserts the rabbit anus with anal clinical thermometer behind the 30min, degree of depth 5cm, every rabbit of thermometric time 2min at least.
Mensuration rabbit normal body temperature meets the requirements in the rear 15min, the slow injection material lixiviating solution of auricular vein, dosage is 10ml/kg, 38 ℃ of lixiviating solution temperature, inject complete after every 1h thermometric 1 time, survey altogether 3 times, to deduct normal body temperature the highest 1 time in 3 body temperature, be the fervescence number of degrees of this rabbit, according to standard the result evaluated.
The body temperature change records of retrial rabbit sees Table 2.5 rabbit fervescence are all below 0.4 ℃, and the intensification total value thinks that below 1.0 ℃ the lacrimal passage stopper material meets pyrogen test requirement, pass the test.
Table 2 test rabbit body temperature change records
4. subcutaneous implant test
24h before the rabbit test cuts off spinal column both sides dorsal body setae.With 3% sodium pentobarbital sodium 1ml/kg, i.v. anaesthetizes.By the conventional requirement iodine disinfection field of operation of surgery.Approximately 4cm makes skin incision in the place in the spinal column both sides, the blunt separation subcutaneous tissue, and a side Implantation Test material, opposite side are implanted contrast with degradable lacrimal passage stopper material (collagen), sew up the incision, and carry out labelling.After implanting for 4 weeks, put to death, take out the hypodermic test material in spinal column both sides and control material, the perusal implant site has or not unusually, cuts the sample subcutaneous tissue of 0.5-1cm on every side, does HE dyeing and identifies.Sample disposal step and HE staining procedure omit, especially in the situation that there is not the microscopy result.
The perusal result, testing of materials group and matched group implant site are showed no obvious redness and fiber enclosed mass, do not find implant and surrounding tissue adhesion when drawing materials.Microscopy the results are shown in Figure 3A, 3B.Fig. 3 A shows that matched group (H.E * 10) structure is normal; 3B shows that test group (H.E * 10) structure is substantially without special change.
Test example 2 normal rabbits are inserted the lacrimal passage stopper test
Method for posting:
(1) 3% pentobarbital sodium is with the capable auricular vein anesthesia of 1ml/kg dosage, and anesthesia level is as the criterion with absent corneal reflex, carries out anterior corneal surface anesthesia with 1% tetracaine before and after the anesthesia, and anesthesia back position is rabbit fixedly;
(2) open rabbit left eye lower eyelid, use the normal saline flushing conjunctival sac, hold the implantation tweezer and through lacrimal point the lacrimal passage stopper total length is inserted in the lacrimal passage;
(3) after anesthesia finishes, will test rabbit and place rabbit-hutch, labelling Implantation Time and eye are not.
20 of New Zealand white rabbit, left eye (L) are inserted lacrimal passage stopper (test eye), and right eye (R) is the contrast eye.A-E group is respectively at inserting rear observation 3 days (3d), 7 days (7d), 2 weeks (2w), January (1m), February (2m), and carries out two and dissect and microscopy.
1. daily observation
After inserting lacrimal passage stopper, A-E group test rabbit is all without unusually showing, and takes food, the drainage situation is normal.
2. anterior chamber of eye is observed
(1) cornea: A-E 20 test eyes of group (L) are 0 order reaction.
(2) 20 tests of lacrimal point: A-E group tear points push and all ooze out without pyorrhea, courage and uprightness etc.
3. histological examination
H.E stained preparation and optics microscopy:
(1) cornea tissue
The cornea tissue of A-E 20 test eyes of group (L) is compared with contrast eye (R) cornea tissue, show no obvious abnormalities, keratocyte and hypothallus are arranged comparison rule, and number does not reach the obvious inflammatory reaction (Fig. 4 A, 4B) such as macrophage without obvious minimizing.
(2) lacrimal passage surrounding tissue
Test group (Fig. 5 A) is compared with matched group (Fig. 5 B), and visible epithelial layer slightly thickens, and a small amount of macrophages infiltration is arranged.
(3) conjunctival tissue
Test group (Fig. 6 A) is compared with matched group (Fig. 6 B), and visible top layer thickens, and a small amount of macrophages infiltration is arranged, but be methodically arranged (Fig. 6 A, 6B).
Cornea specimen electron microscopic examination:
Under the transmission electron microscope, corneal stroma and cellular layer marshalling, number is without minimizing, and organelle is without obvious tumefaction, breakage, visible cavity in the born of the same parents.Each layer of cornea is clear, queueing discipline, matched group and A-E test group no significant difference (Fig. 7 A, 7B).
Test example 3 lacrimal passage stoppers are to the experimental treatment of xerophthalmia
1. the making of xerophthalmia animal model:
The ATD group: eyes drip lincomycin eye liquid, every day 3 times before 10 of the New Zealand white rabbit, art.After 3 days, it is experimental eye that 10 rabbits are all got left eye, and right eye in contrast.3% pentobarbital sodium intraperitoneal anesthesia, experimental eye is local to drip tetracaine twice.Rabbit is fixed in laboratory table, and field of operation 75% alcohol disinfecting spreads hole towel.Cut off temporo side bulbar conjunctiva in fornices, push gently eyeball to the front lower place to expose lacrimal tissue and to give complete excision; Seek rabbit Harderian gland common excretory duct at the nictitating membrance nasal side, and along the whole Harderian gland of the careful complete separation of conduit and complete excision it; At last with the complete excision of nictitating membrance.The postoperative experimental eye is coated with erythromycin eye ointment, lincomycin eye drop eye 3 days.
The E group: eyes drip lincomycin eye liquid, every day 3 times before 10 of the New Zealand white rabbit, art.After 3 days, it is experimental eye that 10 rabbits are all got left eye, and right eye in contrast.3% pentobarbital sodium intraperitoneal anesthesia, experimental eye is local to drip tetracaine twice.Rabbit is fixed in laboratory table, and field of operation 75% alcohol disinfecting spreads hole towel.Using ophthalmologic operation to burn one by one experimental eye with cautery has the tarsal glands opening in the margo palpebrae place up and down, and each opening burns approximately 2 seconds time, burn complete after, with the complete excision of nictitating membrance of rabbit.Art finishes experimental eye and is coated with erythromycin eye ointment.Second day after operation checks that the tarsal glands opening has or not and reopens, then again burnt if any open.
2. lacrimal passage stopper is inserted and effect observation
Insert before the lacrimal passage stopper and insert after carry out general status and observe; 1st, went respectively experimental eye Schirmer I experiment and cornea fluorescent staining in 4,11,18,25,32,40 days; The test of 4th week row tear Ferning and conjunctiva impression cytology check.
(1) inserted behind the lacrimal passage stopper Continuous Observation 3 days, have no the red and swollen inflammatory reaction that waits around the lacrimal point, lacrimal passage stopper is without deviating from phenomenon; Observe to inserting rear the 40th day, the infection sign of part or whole body does not all appear in all experimental rabbits.
(2) Schirmer I test: Schirmer reagent paper blunt end is folded the latter half of of insertion rabbit below conjunctival sac along the broken line place, take out reagent paper after 5 minutes and measure its wet length.The results are shown in Table 3.
Table 3 is inserted lacrimal passage stopper front and back Schirmer I result of the test
Annotate: represent that these data compare difference with the contrast eye statistical significance (P＜0.05) is arranged for * number
As can be seen from Table 3, inserted behind the lacrimal passage stopper the 2nd day, the wet length of 2 groups of different experimental eye Schirmer reagent paper all has increase (P＜0.05) in various degree, and amplification is about 1-2mm, and long term maintenance is at a stable state.
3. cornea fluorescent staining: fluorescein(e) paper is touched lagophthalmos below conjunctival sac, and make it evenly coat whole eye table, under slit lamp cobalt blue light, observe the dyeing situation of cornea, mark by following standard: the mistake CC is made level and with vertical two lines cornea is divided into four districts, each district was by 0,1,2,3 scorings, totally 12 minutes.Wherein 0 is divided into dye-free; 1 is divided into dyeing below 10 points; 2 are divided into dyeing more than 10 points, below 30 points; 3 are divided into dyeing more than 30 points or in the form of sheets.The results are shown in Table 4.
Table 4 is inserted lacrimal passage stopper front and back cornea fluorescent staining result
Annotate: represent that these data compare difference with the contrast eye statistical significance (P＜0.05) is arranged for * number
As seen from Table 4, inserted behind the lacrimal passage stopper approximately 10 days, the experimental eye cornea fluorescent staining integration of 2 group models begins to occur obvious decline (P＜0.05), and As time goes on be steady downward trend, to inserting rear 40 days, the experimental eye cornea of 2 group models has not observed large stretch of fluorescein substantially and dyes the district, and rarely seen choice refreshments shape that is dispersed on a small quantity and dyed; ATD group experimental eye lacrimal river height obviously increases, and seriality is good.
4. tear Ferning test: lacrimal river place under lagophthalmos draws a small amount of tear with glass capillary, places on the microscope slide, and natural drying under the room temperature is at optical microphotograph Microscopic observation crystal habit.Standards of grading: classification is with reference to the Rolando staging.The I level: even, the fine and close crystallization figure of fern shape branch, the space interval between branch is very little; The II level: the numbers of branches of crystallization figure is less, form is less, and the space interval between branch increases; The III level: crystallization figure branch obviously reduces, and the space interval between branch enlarges markedly, and the interval of increase is enough to form new crystallization; IV level: almost do not observe the crystallization figure of fern shape, can only see crystallization a small amount of, indefinite form.
Observation by light microscope as seen, although the tear crystallization of experimental eye still take the crystallization of III level as main, significant change has occured in its form.Before inserting lacrimal passage stopper, the tear crystallization is what be dispersed in, the fuzzy crystallization of fragment shape, and inserting behind the lacrimal passage stopper 40 days, although the space between crystallization is still larger, can forming shaped, fernlike crystal (table 5) comparatively clearly.
Table 5 is inserted the 40th day tear Ferning result of the test behind the lacrimal passage stopper
5. the conjunctiva impression cytology checks: step is as follows:
(1) experimental eye drips one of tetracaine, sucks tear in the lower arched roof with filter paper.
(2) with tweezers the about cellulose acetate filter paper matsurface of 3mm * 2mm size is placed on the outer bulbar conjunctiva of the horizontal 2mm of cornea temporo side down, pressurize gently approximately and to get the top layer epithelial cell with seal in 6 seconds.
(3) with tweezers gripping filter paper wedge angle, filter paper is taken off from conjunctival surface, put into the culture tank that contains 95% ethanol fixative and fix 10 minutes.
(4) the distilled water aquation is 5 minutes.
(5) periodate oxidation is 7 minutes.
(6) the distilled water rinsing is 5 minutes.
(7) Schiff's reagent dyeing is 4 minutes.
(8) the tap water flushing is 5 minutes.
(9) brazilwood extract dyeing is 3 minutes.
(10) 75%, 95% ethanol respectively dewaters twice.
(11) dimethylbenzene is transparent 15 minutes.
(12) resinene mounting places optical microphotograph Microscopic observation goblet cell.
The inspection of conjunctiva impression cytology the results are shown in Figure 7A, 7B.As can be seen from Figure, inserting lacrimal passage stopper front and back conjunctiva impression cytology checks unchanged.
Insert the front conjunctiva impression cytology of lacrimal passage stopper inspection (taking from the ATD group) insert lacrimal passage stopper after 40 days the conjunctiva impression cytology check (with upper figure be same eye)
As mentioned above, by cell toxicity test, hypersensitive test, pyrogen testing, subcutaneous implant test, confirm that the material of lacrimal passage stopper of the present invention and product have good biocompatibility, toxicological test is qualified.As animal model, implant anterior chamber of eye observation and the histological examination of implanting rear 3d to 2m behind the lacrimal passage stopper with new zealand rabbit, find all without obviously organizing inflammatory reaction.To implant this lacrimal passage stopper behind the new zealand rabbit making dry eye model, can obviously improve the xerophthalmia symptom through data show.
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| CN1907507A (en) * | 2006-08-30 | 2007-02-07 | 中国人民解放军军事医学科学院卫生装备研究所 | Lacrimal duct plug and its preparing process and use |
| CN101120901A (en) * | 2007-09-28 | 2008-02-13 | 中山大学中山眼科中心 | Tear duct embolism |
| WO2008035376A2 (en) * | 2006-09-19 | 2008-03-27 | Council Of Scientific & Industrial Research | A novel bio-erodible insert for ophthalmic applications and a process for the preparation thereof |
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| WO2008035376A2 (en) * | 2006-09-19 | 2008-03-27 | Council Of Scientific & Industrial Research | A novel bio-erodible insert for ophthalmic applications and a process for the preparation thereof |
| CN101120901A (en) * | 2007-09-28 | 2008-02-13 | 中山大学中山眼科中心 | Tear duct embolism |
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| Title |
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| 张宏放等.PVA/PVP共混物的聚集态结构.《应用化学》.1990,第07卷(第03期),47-50. * |
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