CN101947307B - Applications of human placenta peptide in preparing drugs for treating dry eye syndrome and other ocular surface diseases - Google Patents
Applications of human placenta peptide in preparing drugs for treating dry eye syndrome and other ocular surface diseases Download PDFInfo
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Abstract
The invention discloses applications of human placenta peptide in preparing drugs for treating simple keratitis, dry eye syndrome, corneal epithelium erosion, corneal alkali burn, various keratititides, LASIK corneal laser surgery and other ocular surface diseases. The experiment proves that the human placenta peptide can increase the tear liquid secretion amount of a dry eye model of New Zealand white rabbits, promote the repairation of corneal epithelium cell damage, increase the quantity of conjunctiva goblet cells, has no stimulation to eyes, and has therapeutic effect on the dry eye model of the New Zealand white rabbit with obvious curative effect, thus the human placenta peptide can be used for treating the dry eye syndrome, the corneal epithelium erosion, corneal epithelium defect, the corneal alkali burn, keratitis and the LASIK corneal laser surgery and the other ocular surface diseases.
Description
Technical field:
The invention belongs to drug world, be specifically related to the application in the eye surface diseases medicine such as behind preparation treatment xerophthalmia, cornea epithelial erosion, corneal epithelial defect, corneal alkali burn, keratitis, LASIK cornea laser operation of people's placenta pepton.
Background technology:
Xerophthalmia is claimed xerophthalmia again, is a kind of common chronic ophthalmic diseases, and this disease can cause the erosion and the inflammation of conjunctiva and corneal epithelium, treats comparatively thornyly, be difficult to cure, and has a strong impact on people's vision and life quality.Topical application artificial tears and somatomedin are the main method of treatment to xerophthalmia; Eye drop commonly used has: hyaluronate sodium eye drop, hydroxypropyl methylcellulose ophthalmic solution, methylcellulose eye drop, polyvinyl alcohol eye drop, polyacrylic acid eye drop, dextran-70 eye drop, epidermal growth factor eye drop, basic fibroblast growth factor eye drop, Solcosery Eye Gel gel for eye use etc.; Above eye drop (or gel) is to promoting the healing of conjunctival epithelium damage; Lubricated eye table; Eye surface diseases such as treatment xerophthalmia have certain assosting effect, but curative effect is not high.Therefore, the emphasis that development treatment xerophthalmia curative effect is high, the little eye drop of side effect is still present research.
People's Placenta Hominis is claimed Placenta Hominis again, is motherland's medical tradition Chinese medicine, has the kidney warming and mends function smart, benefiting QI and nourishing blood, and Placenta Hominis commonly used among the people is well-done edible, to increase Abwehrkraft des Koepers, and various disease conditions such as the treatment body is empty, breath with cough.
People's placenta pepton is isolated a kind of heat labile nonprotein micromolecule polypeptide class material from people's Placenta Hominis, equals reported first in 1985 by Liu Yuexin, and successively uses titles such as placental transfer factor, placental immunity regulatory factor, placenta polypeptide.It has the effect of the body's immunity of adjusting, is usually used in the auxiliary treatment of diseases such as malignant tumor and viral hepatitis clinically.The placenta pepton molecular weight contains 17 seed amino acids and 23 kinds of trace element of needed by human, and contains ribose and polysaccharide etc. less than 10000 dalton, and the physicochemical property of placenta pepton shows that placenta pepton is a kind of nutritious polypeptide formulations.
Summary of the invention:
The purpose of this invention is to provide the application in the eye surface diseases medicine such as behind preparation treatment xerophthalmia, cornea epithelial erosion, corneal epithelial defect, corneal alkali burn, keratitis, LASIK cornea laser operation of people's placenta pepton.
The inventor finds through experiment; People's Placenta Hominis Toplink increases the lacrimal secretion amount of NZw dry eye model, promotes the reparation of its corneal epithelial cell damage and the quantity of increase conjunctiva goblet cell, and to the eye nonirritant; The NZw dry eye model is had therapeutical effect, and evident in efficacy.So eye surface diseases treatments such as people's placenta pepton can be used for behind xerophthalmia, cornea epithelial erosion, corneal epithelial defect, corneal alkali burn, keratitis, the LASIK cornea laser operation, thereby realized the object of the invention.
Eye surface diseases medicine behaviour placenta pepton ophthalmic preparation such as behind described treatment xerophthalmia, cornea epithelial erosion, corneal epithelial defect, corneal alkali burn, keratitis, the LASIK cornea laser operation preferably is made up of with substrate with eye people's placenta pepton of effective dose.People's placenta pepton of effective dose can specifically be selected according to the administration object; The inventor finds through experiment; Merely from curative effect; The therapeutic effect of people's placenta pepton stock solution is best, considers cost, people's placenta pepton treatment time and the osmotic pressure at the eye table, can it be diluted to people's placenta pepton ophthalmic preparation of various concentration with normal saline; These ophthalmic preparations all have therapeutic effect to eye surface diseases such as behind xerophthalmia, cornea epithelial erosion, corneal epithelial defect, corneal alkali burn, keratitis, the LASIK cornea laser operation; Preferably use substrate with eye, mix like thickening agent and use, this thickening agent is selected from but is not limited to hyaluronate sodium, hydroxypropyl methylcellulose sodium, sodium carboxymethyl cellulose, polyvinyl alcohol, macrodex, carbomer, chondroitin sulfate, chitosan.It is simple and convenient to add thickening agent, can directly act on the eye table, and prolong drug has reduced dosage in the holdup time of eye table, has strengthened drug effect.Preferred dose behaviour placenta pepton stock solution accounts for 25～100% (volume fractions) of ophthalmic preparation, and surplus is used adjuvant for eye.
Described ophthalmic preparation can be made into eye with eye drop or gel for eye use, and eye all can directly splash in the conjunctival sac with eye drop or gel for eye use.
People's placenta pepton of the present invention belongs to the material of prior art, can be through the method preparation of prior art.
Essence for a better understanding of the present invention, the pharmacological effect of pharmacological experiment and the result of personnel selection placenta pepton eye surface diseases such as explain that this people's placenta pepton has behind treatment xerophthalmia, cornea epithelial erosion, corneal epithelial defect, corneal alkali burn, keratitis, the LASIK cornea laser operation below.
One, people's placenta pepton is to the influence of NZw dry eye model
1, experiment purpose:
Observe the local therapeutic effect that drips personnel selection placenta pepton eye drop to the NZw dry eye model, explore a kind of new medicine of treatment xerophthalmia.
2, experimental technique:
20 Healthy female NZws are divided into 4 groups at random, (1) normal control group; (2) people's placenta pepton group: 50% (volume fraction) people placenta pepton stock solution+1% (mass fraction) hydroxypropyl emthylcellulose sodium (Hydroxypropyl methyl cellulose; HPMC) mix eye drop treatment group; Its collocation method is: the Sterile Saline (pH is 7.2 ± 0.2) at 0.8% (mass fraction) adds hydroxypropyl emthylcellulose sodium, and equal-volume adds people's placenta pepton stock solution more then, and the whole mass fraction of hydroxypropyl emthylcellulose sodium is 1%; Mix homogeneously is aseptic subpackaged for use then; (3) Solcosery Eye Gel eye gel for treating group is according to the operation instructions operation of Solcosery Eye Gel eye gel; (4) 1% (mass fraction) HPMC vehicle control group, solvent is the Sterile Saline of 0.8% (mass fraction).The white rabbit of normal control group is left intact; All the other 3 groups of white rabbits are extractd lachrymal gland, the 3rd eyelid and Harder ' the s gland of left eye; And with the calcination of 50% (volume fraction) trichloroacetic acid up and down fornical conjunctiva make dry eye model, right eye is left intact, the 56d left eye begins to drip and treats with above-mentioned different pharmaceutical after the modeling; Every day 4 times, continuous use 28d.Before modeling, 7d, 28d and 56d after the modeling, and 14d, 28d carry out Shirmer I test, 1% fluorescent staining and the cytolgical examination of conjunctiva trace after the medication, 28d gets cornea, the capable pathological examination of conjunctiva after the medication.
3, experimental result:
Shown in table 1, table 2, table 3 and table 4,56d after the modeling, the Shirmer I test value of NZw and conjunctiva goblet cell number count result show that be shown in table 1 and table 2, each processed group is starkly lower than normal group, P＜0.01; Cornea fluorescent staining integration and Nelson integration are shown in table 3 and table 4, and each processed group is apparently higher than normal group, and P＜0.01 is explained the NZw dry eye model modeling success of each processed group thus.14d and 28d after the medication, the Shirmer I test value of people's placenta pepton group and Solcosery Eye Gel group and goblet cell quantity rise appreciably before than medication or increase, and P＜0.01 is shown in table 1 and table 2; Cornea fluorescent staining integration and Nelson integration obviously reduce before than medication, and P＜0.05 or P＜0.01 is shown in table 3 and table 4; The various inspection indexs of two treatment groups are compared with the HPMC group all has notable difference, P＜0.05 or P＜0.01.Pathologic finding shows that see Fig. 1 and Fig. 2, Figure 1A is a normal rabbit cornea pathological section, visible 5 layers of corneal epithelial cell; Form is clear, arrangement is tight (HE dyeing, * 400), and Figure 1B is the 28th a Lepus cornea pathological section after the medication of people's placenta pepton group, visible corneal epithelium attenuation; Be merely 3 layers (HE dyeing, * 400), Fig. 1 C is the 28th a Lepus cornea pathological section after the medication of Solcosery Eye Gel group, visible corneal epithelium attenuation; 2～3 layers, the degeneration of part epithelial cell, (the HE dyeing of part basal cell edema; * 400), Fig. 1 D is the 28th a Lepus cornea pathological section after the medication of HPMC group, visible corneal epithelium attenuation; The subregion disappearance is not seen basal layer cell (HE dyeing, * 400).Fig. 2 A is a normal rabbit conjunctiva pathological section, visible conjunctival epithelium and columnar epithelium marshalling, and goblet cell is intensive, is rich in secretory granule (HE dyeing, * 400); The 28th Lepus conjunctiva pathological section after the medication of Fig. 2 B people placenta pepton group, visible conjunctival epithelial cell layer attenuation, the goblet cell comparatively dense is rich in secretory granule (HE dyeing, * 400); The 28th day conjunctiva pathological section after the medication of Fig. 2 C Solcosery Eye Gel group, visible conjunctival epithelial cell layer attenuation, a small amount of goblet cell (HE dyeing, * 400); The 28th day conjunctiva pathological section after the medication of Fig. 2 D HPMC group, visible conjunctival epithelial cell layer attenuation, goblet cell quantity few (HE dyeing, * 400).This shows that behind people's placenta pepton eye drop and the Solcoseryl Eye-Gel medication 28d, conjunctival epithelium thickens than the HPMC group, form is rule, and the conjunctiva goblet cell increases than the HPMC group.
SIt check the value result before and after the treatment of table 1 white rabbit dry eye model (n=5, ± s)
Annotate:
*P＜0.01or
* *P＜0.001vs normal group, ▲ ▲ P＜0.01vs same group before treatment, △ P＜0.05 or △ △ P＜0.01 vs HPMC group after treatment.
Conjunctiva goblet cell quantity result (n=5,
± s) before and after the treatment of table 2 white rabbit dry eye model
Annotate:
* *P＜0.001 vs normal group, ▲ ▲ P＜0.01 vs model group, △ P＜0.05 vs HPMC group at the 14th and 28thdays after treatment.
Cornea fluorescein integral result (n=5,
± s) before and after the treatment of table 3 white rabbit dry eye model
Annotate:
*P＜0.01 or
* *P＜0.001 vs normal group; ▲ P＜0.05or ▲ ▲ P＜0.01 vs same group before treatment; △ P＜0.05, △ △ P＜0.01 vs or △ △ △ P＜0.001 vs HPMC group at the 14th and 28th days after treatment.
Nelson classification integration situation (n=5,
± s) before and after the treatment of table 4 white rabbit dry eye model
Annotate:
* *P＜0.001vs normal group, ▲ P＜0.05or ▲ ▲ P＜0.01 vs same group before treatment, △ P＜0.05 vsHPMC group at the 14th and 28th day after treatment.
4, experiment conclusion:
56d successfully sets up the white rabbit dry eye model after the modeling, and people's placenta pepton eye drop can increase the lacrimal secretion amount of white rabbit dry eye model, promotes the reparation of its corneal epithelial cell damage and the quantity of increase conjunctiva goblet cell.This shows that people's placenta pepton has therapeutical effect to the NZw dry eye model, and evident in efficacy, the treatment of eye surface diseases such as can be used for behind xerophthalmia, cornea epithelial erosion, corneal epithelial defect, corneal alkali burn, keratitis, the LASIK cornea laser operation.
Two, the eye local irritation experimentation of people's placenta pepton ophthalmic preparation
1, experiment purpose:
Observe the animal eyes contact and tried the IR situation that produced behind the thing.
2, experimental technique:
2.1: experimental animal: NZw, 12, body weight 1.5～2.5Kg is divided into 2 groups at random, and 6 every group, one group is people's placenta pepton eye drop irritation test group, and another group is thickening people placenta pepton eye drop irritation test group.In people's placenta pepton eye drop irritation test group, the white rabbit left eye placenta pepton stock solution of should choosing, right eye is used normal saline and is compared; In thickening people placenta pepton eye drop irritation test group; The white rabbit left eye is used 50% (volume fraction) people placenta pepton stock solution+1.0% (mass fraction) hydroxypropyl emthylcellulose sodium+50% normal saline (volume fraction) eye drop; Right eye application quality mark be 1.0% hydroxypropyl emthylcellulose sodium eye drop as contrast, solvent is a normal saline;
2.2 tried thing: people's placenta pepton ophthalmic preparation comprises people's placenta pepton eye drop, thickening people placenta pepton eye drop, normal saline, excipient (mass fraction is 1.0% hydroxypropyl emthylcellulose sodium eye drop).
2.3 concrete experimental technique: will be tried thing and splash in the side rabbit conjunctival capsule, dosage is 0.1ml, opposite side is done normal saline or excipient (mass fraction is 1.0% hydroxypropyl emthylcellulose sodium gel for eye use) contrast.Give tried thing after, with hands with the passive closed 5～10s of rabbit eyelid, every day 4 times, 14d continuously.The local response situation tried 6h behind the thing, 12h, 24h, 48h, 72h, 7d, 10d and 14d given in record.
3, the result judges and estimates:
Press table 5 scoring.IR score value addition with each horn film, iris and conjunctiva is total mark.With total mark and divided by number of animals, be the last score value of eye irritation.Try to achieve with the method, stimulate score value for the eye tried 6h behind the thing, 12h, 24h, 48h, 72h, 7d, 10d and 14d, press table 5, table 6 standard, judgement is tried the eye irritation degree of thing.
Table 5 an IR scoring
Table 6 a stimulation evaluation criterion
4, result of the test: people's placenta pepton ophthalmic preparation is seen table 7, table 8 to rabbit eye irritation result of the test
Table 7 people placenta pepton eye drop dialogue lagophthalmos irritant test result
Continuous table 7
Continuous table 7
Continuous table 7
Table 8 thickening people placenta pepton eye drop dialogue lagophthalmos irritant test result
Continuous table 8
Continuous table 8
Continuous table 8
5, experiment conclusion: can learn by above-mentioned result of the test; People's placenta pepton ophthalmic preparation of the present invention; No matter be people's placenta pepton eye drop or thickening people placenta pepton eye drop, its eye irritation test integration＜3, therefore people's placenta pepton of the present invention is that anophthalmia is irritating.
In sum; People's Placenta Hominis Toplink of the present invention increases the lacrimal secretion amount of NZw dry eye model, promotes the reparation of its corneal epithelial cell damage and the quantity of increase conjunctiva goblet cell, and to the eye nonirritant; The NZw dry eye model is had therapeutical effect, evident in efficacy.So people's placenta pepton of the present invention such as can be used for behind xerophthalmia, cornea epithelial erosion, corneal epithelial defect, corneal alkali burn, keratitis, the LASIK cornea laser operation at the eye surface diseases treatment.
From above result, can draw and the invention has the advantages that:
(1) the raw material people Placenta Hominis of people's placenta pepton of the present invention is taken from healthy puerpera's Placenta Hominis, at first will carry out the screening of diseases such as the first and second the third hepatitis Ds, AIDS, syphilis to puerpera and Placenta Hominis blood, has reduced the risk of viral infection; And virus, antibody, multiple hormone and enzyme equimolecular quantity can not be passed through dialyzer greater than 10000 dalton in the Placenta Hominis homogenate, have further guaranteed the safety of the eye drop of preparation.
(2) draw materials and be healthy puerpera's Placenta Hominis, people's placenta pepton ophthalmic preparation of preparation is close with the human serum composition, more approaches human body; But the molecular weight of placenta pepton is less; Do not have the existence of the immunoglobulins macromolecular substances in the serum, therefore, people's placenta pepton is used and is the people; It is very little that anaphylactoid probability takes place between of the same race, and the absorption by human body utilization rate is higher.
People's placenta pepton of the present invention is found through zoopery; The lacrimal secretion amount that it can increase the NZw dry eye model promotes the reparation of its corneal epithelial cell damage and the quantity of increase conjunctiva goblet cell, and to the eye nonirritant; The NZw dry eye model had therapeutical effect; Therefore evident in efficacy, pharmacological action is strong, the treatment of eye surface diseases such as can be used for behind xerophthalmia, cornea epithelial erosion, corneal epithelial defect, corneal alkali burn, various keratitis, the LASIK cornea laser operation.
Description of drawings:
Fig. 1 is the cornea pathology slice map of NZw normal group and each processed group;
Fig. 2 is the conjunctiva pathological section figure of NZw normal group and each processed group.
The specific embodiment:
Below be to further specify to of the present invention, rather than limitation of the present invention.
One, the preparation of people's placenta pepton stock solution:
Select all negative healthy puerpera's Placenta Hominiss such as antenatal Serological testing HIV, hepatitis B virus, hepatitis C virus, syphilis.Every Placenta Hominis of suffering from the puerpera of diseases such as infectious hepatitis, AIDS, syphilis, and the Placenta Hominis of artificial abortion, stillborn fetus, various teratogenesis etc. does not all use.Under aseptic condition, place on the ice face immediately after Placenta Hominis is given birth to and take back rapidly, also can in collecting transportation, also answer cold preservation, if should in 3 months, use with Placenta Hominis cold preservation below-10 ℃ at the freezing Placenta Hominis below-30 ℃.The Cord blood of getting Placenta Hominis carries out detections such as HIV, hepatitis B virus, hepatitis C virus, syphilis, and all negative Placenta Hominis of above index can be chosen application.
On super-clean bench,,, remove remaining bloodstain with the fresh human placenta that the medical saline flushing of pre-cooling is taken back for twice according to the aseptic standard of cell culture; Cut off amniotic membrane, umbilical cord, Placenta Hominis is shredded weigh, volume ratio adds the physiological saline solution of pre-cooling at 2: 1 by weight; 10000 rev/mins are stirred homogenate 3 times, and each 3 minutes, intermittently 5 minutes; During this time around the cold pack cold compress agitator; Homogenate is poured in the 1000ml beaker, and 2: 1 physiological saline solution of volume ratio washes the agitator inwall 3 times by weight again, puts refrigerator below-30 ℃ and preserves.
More than 5 times, solidification point is below-30 ℃ with the homogenate multigelation, and melt temperature should be above 25 ℃.The multigelation process is that cell crashing ratio should reach more than 90% with cell breakage in the Placenta Hominis homogenate.
Homogenate with above-mentioned multigelation under the aseptic condition carries out centrifugal; Collect supernatant after centrifugal 30 minutes for 4 ℃ following 4000 rev/mins and put into bag filter, sealing bag filter opening places outside the beaker; The bag filter that the Placenta Hominis supernatant is housed is put into the beaker of 1000ml; By 1: 1 volume physiological saline solution is added in the beaker, the submergence bag filter is put 4 ℃ of refrigerators and is dialysed.Collected dialysis solution in 24 hours, then with dialysis solution through 0.2 μ m filtering with microporous membrane degerming, again through UV spectrophotometer measuring, placenta pepton stock solution has 2 absworption peaks, one at the 202nm place, one at the 256nm place.260nm/280nm spectral absorption value＞2.0,260nm spectral absorption value＞10.0, detecting qualified promptly is people's placenta pepton stock solution ,-20 ℃ of preservations are subsequent use after the packing.
One, the preparation of people's placenta pepton eye drop
The preparation of embodiment 1,50% (volume fraction) people placenta pepton eye drop
People's placenta pepton stock solution 500ml
Sodium chloride 4g
The 1mol/L sodium hydroxide is an amount of
Water for injection adds to 1000ml
Get 4g sodium chloride and add an amount of water for injection and make its dissolving, stir, using 1mol/L sodium hydroxide adjust pH is 7.2 ± 0.2; The people's placenta pepton stock solution that adds 500ml again, restock water for injection is to 1000ml, the membrane filtration degerming of via hole diameter 0.2 μ m; Aseptic subpackaged, every 0.5ml.
Two, the preparation of thickening people placenta pepton eye drop
The preparation of embodiment 2,25% (volume fraction) people placenta pepton stock solution+0.1% (mass fraction) hyaluronate sodium eye drop
People's placenta pepton stock solution 250ml
Sodium chloride 6.0g
Hyaluronate sodium 1g
The 1mol/L sodium hydroxide is an amount of
Water for injection adds to 1000ml
Get 6.0g sodium chloride and add an amount of water for injection and make its dissolving, stir, using 1mol/L sodium hydroxide adjust pH is 7.2 ± 0.2, adds the 1g hyaluronate sodium again; Immersion makes its swelling, stirring and evenly mixing, autoclave sterilization 30 minutes; Cooling, polishing sterile water for injection are to 750ml, and aseptic condition adds people's placenta pepton stock solution of 250ml down; Mixing, aseptic subpackaged, every 0.5ml.
The preparation of embodiment 3,50% (volume fraction) people placenta pepton stock solution+0.5% (mass fraction) hydroxypropyl emthylcellulose sodium eye drop
People's placenta pepton stock solution 500ml
Sodium chloride 4.0g
Hydroxypropyl emthylcellulose sodium 5g
The 1mol/L sodium hydroxide is an amount of
Water for injection adds to 1000ml
Get 4.0g sodium chloride and add an amount of water for injection and make its dissolving, stir, using 1mol/L sodium hydroxide adjust pH is 7.2 ± 0.2, adds 5g hydroxypropyl emthylcellulose sodium again; Immersion makes its swelling, stirring and evenly mixing, autoclave sterilization 30 minutes; Cooling, polishing sterile water for injection are to 500ml, and aseptic condition adds people's placenta pepton stock solution of 500ml down; Mixing, aseptic subpackaged, every 0.5ml.
The preparation of embodiment 4,75% (volume fraction) people placenta pepton stock solution+1.4% (mass fraction) polyvinyl alcohol eye drop
People's placenta pepton stock solution 750ml
Sodium chloride 2.0g
Polyvinyl alcohol 14g
The 1mol/L sodium hydroxide is an amount of
Water for injection adds to 1000ml
Get 2.0g sodium chloride and add an amount of water for injection and make its dissolving, stir, using 1mol/L sodium hydroxide adjust pH is 7.2 ± 0.2, adds the 14g polyvinyl alcohol again; Immersion makes its swelling, stirring and evenly mixing, autoclave sterilization 30 minutes; Cooling, polishing sterile water for injection are to 250ml, and aseptic condition adds people's placenta pepton stock solution of 750ml down; Mixing, aseptic subpackaged, every 0.5ml.
The preparation of embodiment 5,12.5% (volume fraction) people placenta pepton stock solution+0.2% (mass fraction) carbomer eye drop
People's placenta pepton stock solution 125ml
Sodium chloride 7.0g
Carbomer 2g
The 1mol/L sodium hydroxide is an amount of
Water for injection adds to 1000ml
Get 7.0g sodium chloride and add an amount of water for injection and make its dissolving, stir, add to the full amount of water for injection, using 1mol/L sodium hydroxide adjust pH is 7.2 ± 0.2; Add the 2g carbomer again, immersion makes its swelling, stirring and evenly mixing, autoclave sterilization 30 minutes; Cooling, polishing sterile water for injection are to 875ml, and aseptic condition adds people's placenta pepton stock solution of 125ml down; Mixing, aseptic subpackaged, every 0.5ml.
The preparation of embodiment 6,25% (volume fraction) people placenta pepton stock solution+0.5% (mass fraction) chitosan eye drop
People's placenta pepton stock solution 250ml
Sodium chloride 6.0g
Chitosan 5g
The 1mol/L sodium hydroxide is an amount of
Water for injection adds to 1000ml
Get 6.0g sodium chloride and add an amount of water for injection and make its dissolving, stir, using 1mol/L sodium hydroxide adjust pH is 7.2 ± 0.2, adds the 5g chitosan again; Immersion makes its swelling, stirring and evenly mixing, autoclave sterilization 30 minutes; Cooling, polishing sterile water for injection are to 750ml, and aseptic condition adds people's placenta pepton stock solution of 250ml down; Mixing, aseptic subpackaged, every 0.5ml.
Three, the preparation of placenta pepton gel for eye use
Embodiment 7,50% (volume fraction) people placenta pepton stock solution+2.0% (mass fraction) hydroxypropyl emthylcellulose sodium gel for eye use
People's placenta pepton stock solution 500ml
Hydroxypropyl emthylcellulose sodium 20g
Sodium chloride 4g
The 1mol/L sodium hydroxide is an amount of
Water for injection adds to 1000ml
Get 4.0g sodium chloride and add an amount of water for injection and make its dissolving, stir, using 1mol/L sodium hydroxide adjust pH is 7.2 ± 0.2, adds 20g hydroxypropyl emthylcellulose sodium again; Immersion makes its swelling, stirring and evenly mixing, autoclave sterilization 30 minutes; Cooling, polishing sterile water for injection are to 500ml, and aseptic condition adds people's placenta pepton stock solution of 500ml down; Mixing, aseptic subpackaged, every 0.5ml.
Embodiment 8,12.5% (volume fraction) people placenta pepton stock solution+0.3% (mass fraction) hyaluronic acid sodium gel for eye use
People's placenta pepton stock solution 125ml
Hyaluronic acid sodium 3g
Sodium chloride 7g
The 1mol/L sodium hydroxide is an amount of
Water for injection adds to 1000ml
Get 7.0g sodium chloride and add an amount of water for injection and make its dissolving, stir, using 1mol/L sodium hydroxide adjust pH is 7.2 ± 0.2, adds the 3g hyaluronic acid sodium again; Immersion makes its swelling, stirring and evenly mixing, autoclave sterilization 30 minutes; Cooling, polishing sterile water for injection are to 875ml, and aseptic condition adds people's placenta pepton stock solution of 125ml down; Mixing, aseptic subpackaged, every 0.5ml.
Embodiment 9,25% (volume fraction) people placenta pepton stock solution+0.4% (mass fraction) carbomer gel for eye use
People's placenta pepton stock solution 250ml
Carbomer 4g
Sodium chloride 6g
The 1mol/L sodium hydroxide is an amount of
Water for injection adds to 1000ml
Get 6.0g sodium chloride and add an amount of water for injection and make its dissolving, stir, using 1mol/L sodium hydroxide adjust pH is 7.2 ± 0.2, adds the 4g carbomer again; Immersion makes its swelling, stirring and evenly mixing, autoclave sterilization 30 minutes; Cooling, polishing sterile water for injection are to 750ml, and aseptic condition adds people's placenta pepton stock solution of 250ml down; Mixing, aseptic subpackaged, every 0.5ml.
Claims (3)
1. the application of people's placenta pepton in preparation treatment xerophthalmia and cornea epithelial erosion medicine.
2. application according to claim 1 is characterized in that, described treatment xerophthalmia and cornea epithelial erosion medicine behaviour placenta pepton ophthalmic preparation, and its people's placenta pepton that comprises effective dose is used adjuvant with eye.
3. application according to claim 2; It is characterized in that; Described eye comprises thickening agent with adjuvant, and this thickening agent is selected from hyaluronate sodium, hydroxypropyl methylcellulose sodium, sodium carboxymethyl cellulose, polyvinyl alcohol, macrodex, carbomer, chondroitin sulfate or chitosan.
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| CN102266354A (en) * | 2011-07-26 | 2011-12-07 | 贵州泰邦生物制品有限公司 | Method for preparing raw materials for preparing placenta polypeptide injection |
| CA2977562C (en) * | 2015-02-25 | 2019-12-03 | Tsung-Chuan Ho | Use of short synthetic peptide for the treatment and/or prophylaxis of dry eye disease |
| CN105396125A (en) * | 2015-11-26 | 2016-03-16 | 山东省眼科研究所 | Application of IL-6 to repairing of corneal epithelial injuries |
| CN116445370B (en) * | 2023-06-12 | 2023-08-22 | 山东中科嘉亿生物工程有限公司 | Bifidobacterium breve JYBF-117 for relieving xerophthalmia and microbial inoculum and application thereof |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP1118329A1 (en) * | 1998-09-28 | 2001-07-25 | Santen Pharmaceutical Co., Ltd. | Lacrimal secretion promoters or eye drops for treating keratoconjunctival failure containing as the active ingredient natriuretic peptides |
| CN101658491A (en) * | 2009-09-24 | 2010-03-03 | 哈尔滨医科大学 | Amnion eye drops for curing cornea alkali burn |
-
2010
- 2010-08-19 CN CN2010102589328A patent/CN101947307B/en not_active Expired - Fee Related
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP1118329A1 (en) * | 1998-09-28 | 2001-07-25 | Santen Pharmaceutical Co., Ltd. | Lacrimal secretion promoters or eye drops for treating keratoconjunctival failure containing as the active ingredient natriuretic peptides |
| CN101658491A (en) * | 2009-09-24 | 2010-03-03 | 哈尔滨医科大学 | Amnion eye drops for curing cornea alkali burn |
Non-Patent Citations (1)
| Title |
|---|
| 郭立涛.羊胎盘肽免疫活性研究.《中国优秀硕士论文全文数据库 农业科技辑》.2006,(第10期),全文. * |
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| Publication number | Publication date |
|---|---|
| CN101947307A (en) | 2011-01-19 |
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