CN103933549A - Novel blood vessel chalone eye drop and preparation method thereof - Google Patents
Novel blood vessel chalone eye drop and preparation method thereof Download PDFInfo
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- CN103933549A CN103933549A CN201310019428.6A CN201310019428A CN103933549A CN 103933549 A CN103933549 A CN 103933549A CN 201310019428 A CN201310019428 A CN 201310019428A CN 103933549 A CN103933549 A CN 103933549A
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- eye drop
- angiostatin
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- phosphate buffer
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Abstract
The invention belongs to the technical field of drugs, and relates to a blood vessel chalone eye drop which can be used for preventing and treating neovascular diseases in an ophthalmology department. According to the formula, the eye drop comprises 0.01% of recombination human Kringlel-3 blood vessel chalone, 0.1% of eye drop level sodium hyaluronate, 0.01% of benzalkonium chloride, 0.1% of EDTA-Na2 and a phosphate buffer solution, wherein the phosphate buffer solution comprises 0.8% of NaCL, 0.02% of KCL, 0.363% of Na2HPO4 12H2O, 0.024% of KH2PO4, and the balance distilled water. The eye drop has the advantages of being even in tissue distribution, high in wetting and lubrication action, good in stability and the like, and can be used for preventing and treating neovascular diseases, such as the eye retina and corneal neovascularization disease and the choroid membrane neovascularization disease, in the ophthalmology department.
Description
Technical field: the invention belongs to field of pharmaceutical technology, is a kind of eye drop that can prevent and treat ophthalmology neovascular diseases.
Background technology: it is the typical pathologic change of ophthalmology neovascular diseases that ocular angiogenesis forms, comprise eyes retina new vessels pathological changes, corneal leukoma, new vessels formative glaucoma and choroidal neovascularization of by diabetes etc., being caused etc., if protracted inflammation and malpractice can cause patient's vision, degradation is even blind.Current, the means such as ophthalmology laser and photosensitization therapy clinically be applied in formation and the development that can suppress to a certain extent ocular angiogenesis, but often can lead eye, cause the impaired and easily recurrence of normal structure, medical expense is high simultaneously.The means of finding a kind of new determined curative effect and treatment ophthalmology neovascular diseases with low cost become study hotspot.
Angiostatin (angiostatin, AS) is a kind of endogenic neovascularization inhibitor, has the effect of specific inhibition vascular endothelial proliferation.Research is found, angiostatin is the interior segments of fibrinolysis proenzyme, fibrinolysis proenzyme has 5 tricyclic structures, be kringle domain (K1, K2, K3, K4 and K5), the action site that has different activator of plasminogens on the diverse location that plasminogen pepsinogen albumen connects, different activator of plasminogens acts on plasminogen and will produce the angiostatin of different molecular formation.Attested angiostatin has 5 kinds of K1-3, K4, K1-4, K1-4.5 and K5 etc. at present.Multinomial experimentation confirms, angiostatin has obvious inhibitory action to retinal microvascular endotheli ocytosis and retinal neovascularization and cornea rebirth blood vessel.The specific inhibitory effect that the present invention forms ocular angiogenesis in view of angiostatin, a kind of new angiostatin eye drop has been prepared in design, for treatment ophthalmology neovascular diseases provides useful reference.
Angiostatin suppresses the physiological function that ocular angiogenesis forms and is confirmed, however take angiostatin be crude drug preparation treatment ocular neovascular diseases angiostatin eye drop research still seldom.There is scholar to adopt PBS etc. to prepare people Kringle1-5 and recombinant human Kringle5 albumen eye drop for excipient, but adjuvant is selected limitation, do not consider physiological characteristics and physicochemical property that angiostatin itself is special, preparation technology is simple, have no relevant Quality control, the research that the recombinant human Kringle 1-3 of take prepares angiostatin eye drop as crude drug has no first pass report especially.In view of angiostatin is the protide biological active substances in body, itself there is special physicochemical property, the recombinant human Kringle 1-3 of take is example, its dry lyophilized powder is suitable preserves the long period under-20 ℃ of conditions, bad at 2-8 ℃ of condition stability inferior, once heavy water-soluble, stability is poorer; In addition, prepare after eye drop appropriate pH and viscosity and preserve lower antiseptic and inhibiting bacteria function and also need consideration for a long time.The present invention has considered above-mentioned factor,
Consider the features such as recombinant human Kringle 1-3 good water solubility, poor stability, the biological active substances of genus protide, prepared a kind of new recombinant human Kringle 1-3 angiostatin eye drop.
The object of the invention is: a kind of eye drop that can be used for treating ocular neovascular diseases is provided, this eye drop have tissue distribution evenly, moistening and the advantage such as lubrication is strong, stability is better, and provide the preparation method of this eye drop.
Summary of the invention: the object of the present invention is to provide a kind of angiostatin eye drop that can be used for treating ocular neovascular diseases, this eye drop have tissue distribution evenly, moistening and the advantage such as lubrication is strong, stability is better, and provide the preparation method of this eye drop.
The present invention is specially:
(1) preparation of buffer system: standby in right amount according to following formula preparation phosphate solution: (1000ml)
(2) selection of formula
(3) preparation technology
Eye drop level hyaluronic acid sodium (MW 1683200) is joined in the phosphate buffer (PBS) of proper volume by the consumption of 0.1% preparation amount, dissolve standby.Take the benzalkonium chloride of 0.01% preparation amount, be dissolved in the phosphate buffer (PBS) of proper volume, add hyaluronic acid sodium solution, adding wherein mass fraction is 0.1% EDTA-Na
2, fully mix, add distilled water to preparation amount, obtain angiostatin eye drop excipient solution.Angiostatin eye drop excipient solution is obtained to aseptic angiostatin eye drop excipient solution with 0.22 μ m microporous filter membrane aseptic filtration in superclean bench, measure the aseptic excipient solution of proper volume and dissolve appropriate recombinant human Kringle 1-3 angiostatin crude drug, vortex shakes to clear, preparation mass fraction is that 0.01% (being that mass concentration is 100 μ g/ml) angiostatin eye drop is some, encapsulation, obtains recombinant human Kringle 1-3 angiostatin eye drop of the present invention.
Beneficial effect of the present invention: (1) the present invention has prepared a kind of new angiostatin eye drop that recombinant human Kringle 1-3 is crude drug of take, and can suppress ocular angiogenesis and form, and can be used for treating ocular neovascular diseases.(2) the present invention has adopted the thickening agent of hyaluronic acid sodium as eye drop, has improved the viscosity of eye drop, has extended the eye drop ophthalmic holdup time, promotes eye drop absorption and distribution within the eye; Meanwhile, hydrophilic ability, lubrication and histocompatibility that hyaluronic acid sodium is good, be beneficial to the malaise symptoms that alleviates and eliminate eye, and Draize rabbit irritant experiment research shows, the eye drop that the present invention makes is to rabbit eye nonirritant.(3) in the present invention, disodiumedetate (EDTA-Na
2) as stabilizing agent, join in preparation prescription, study on the stability finds that recombinant human Kringle 1-3 angiostatin eye drop stability obviously improves; (4) in the present invention, the benzalkonium chloride of suitable concentration has solved the protide eye drop problem that possible microbiological contamination is polluted in preservation process; (5) in preparation technology of the present invention, phosphate buffer (PBS) has guaranteed pH value and the osmotic pressure that eye drop is suitable, the recombinant human Kringle1-3 angiostatin eye drop pH value making is 7.35, osmotic pressure is consistent with physiological status, meets 2010 editions relevant regulations about eye drop pH and osmotic pressure of < < Chinese Pharmacopoeia > >.
Claims (7)
1. an angiostatin eye drop composition, said composition is to be dissolved in phosphate buffer and to be obtained by recombinant human Kringle1-3 angiostatin, hyaluronic acid sodium, benzalkonium chloride, disodiumedetate.
2. the compositions of claim 1, is characterized in that take that recombinant human Kringle1-3 angiostatin is principal agent, and content is 0.01% (100 μ g/ml).
3. the compositions of claim 1, is characterized in that with eye drop level hyaluronic acid sodium, as thickening agent, content is 0.1%.
4. the compositions of claim 1, is characterized in that with benzalkonium chloride, as antiseptic and inhibiting bacteria function agent, content is 0.01%.
5. the compositions of claim 1, is characterized in that with disodiumedetate (EDTA-Na
2) as stabilizing agent, content is 0.1%.
6. the compositions of claim 1, is characterized in that with phosphate buffer, as solvent, the concrete content of each component is: NaCL0.8%, KCL0.02%, Na
2hPO
412H
2o0.363%, KH
2pO
40.024%, all the other are distilled water.
7. the compositions of claim 1, its preparation method is that eye drop level hyaluronic acid sodium (MW 1683200) is joined in the phosphate buffer (PBS) of proper volume by the consumption of 0.1% preparation amount, dissolves standby.Take the benzalkonium chloride of 0.01% preparation amount, be dissolved in the phosphate buffer (PBS) of proper volume, add hyaluronic acid sodium solution, adding wherein mass fraction is 0.1% EDTA-Na
2, fully mix, add distilled water to preparation amount, obtain angiostatin eye drop excipient solution.Angiostatin eye drop excipient solution is obtained to aseptic angiostatin eye drop excipient solution with 0.22 μ m microporous filter membrane aseptic filtration in superclean bench, measure the aseptic excipient solution of proper volume and dissolve appropriate recombinant human Kringle1-3 angiostatin crude drug, vortex shakes to clear, preparation mass fraction is that 0.01% (being that mass concentration is 100 μ g/ml) angiostatin eye drop is some, encapsulation, obtains.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201310019428.6A CN103933549A (en) | 2013-01-17 | 2013-01-17 | Novel blood vessel chalone eye drop and preparation method thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201310019428.6A CN103933549A (en) | 2013-01-17 | 2013-01-17 | Novel blood vessel chalone eye drop and preparation method thereof |
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| CN103933549A true CN103933549A (en) | 2014-07-23 |
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| Application Number | Title | Priority Date | Filing Date |
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| CN201310019428.6A Pending CN103933549A (en) | 2013-01-17 | 2013-01-17 | Novel blood vessel chalone eye drop and preparation method thereof |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109562123A (en) * | 2016-05-24 | 2019-04-02 | 萨勒普塔医疗公司 | Phosphoric acid diamides morpholino oligomers pharmaceutical composition |
-
2013
- 2013-01-17 CN CN201310019428.6A patent/CN103933549A/en active Pending
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109562123A (en) * | 2016-05-24 | 2019-04-02 | 萨勒普塔医疗公司 | Phosphoric acid diamides morpholino oligomers pharmaceutical composition |
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Application publication date: 20140723 |