CN102631318B - Preparation method of indometacin liposome eye drops - Google Patents
Preparation method of indometacin liposome eye drops Download PDFInfo
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- CN102631318B CN102631318B CN2012100720535A CN201210072053A CN102631318B CN 102631318 B CN102631318 B CN 102631318B CN 2012100720535 A CN2012100720535 A CN 2012100720535A CN 201210072053 A CN201210072053 A CN 201210072053A CN 102631318 B CN102631318 B CN 102631318B
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- boric acid
- indomethacin
- borax
- lipid
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- CGIGDMFJXJATDK-UHFFFAOYSA-N indomethacin Chemical compound CC1=C(CC(O)=O)C2=CC(OC)=CC=C2N1C(=O)C1=CC=C(Cl)C=C1 CGIGDMFJXJATDK-UHFFFAOYSA-N 0.000 title claims abstract description 79
- 229960000905 indomethacin Drugs 0.000 title claims abstract description 44
- 239000003889 eye drop Substances 0.000 title claims abstract description 33
- 238000002360 preparation method Methods 0.000 title claims abstract description 32
- 239000002502 liposome Substances 0.000 title claims abstract description 28
- 229940012356 eye drops Drugs 0.000 title claims abstract description 21
- 229910021538 borax Inorganic materials 0.000 claims abstract description 28
- 239000004328 sodium tetraborate Substances 0.000 claims abstract description 28
- 235000010339 sodium tetraborate Nutrition 0.000 claims abstract description 28
- KGBXLFKZBHKPEV-UHFFFAOYSA-N boric acid Chemical compound OB(O)O KGBXLFKZBHKPEV-UHFFFAOYSA-N 0.000 claims abstract description 26
- 239000004327 boric acid Substances 0.000 claims abstract description 26
- 239000007853 buffer solution Substances 0.000 claims abstract description 17
- 239000000243 solution Substances 0.000 claims abstract description 15
- BTBUEUYNUDRHOZ-UHFFFAOYSA-N Borate Chemical compound [O-]B([O-])[O-] BTBUEUYNUDRHOZ-UHFFFAOYSA-N 0.000 claims abstract description 14
- 150000001875 compounds Chemical class 0.000 claims abstract description 10
- -1 sterol lipid Chemical class 0.000 claims abstract description 9
- 239000012528 membrane Substances 0.000 claims abstract description 6
- 230000001954 sterilising effect Effects 0.000 claims abstract description 5
- 238000001914 filtration Methods 0.000 claims abstract description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 23
- 150000002632 lipids Chemical class 0.000 claims description 20
- 239000002131 composite material Substances 0.000 claims description 16
- 150000003904 phospholipids Chemical class 0.000 claims description 16
- 229930193551 sterin Natural products 0.000 claims description 16
- 238000000034 method Methods 0.000 claims description 15
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 12
- GVJHHUAWPYXKBD-UHFFFAOYSA-N (±)-α-Tocopherol Chemical compound OC1=C(C)C(C)=C2OC(CCCC(C)CCCC(C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-UHFFFAOYSA-N 0.000 claims description 8
- HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 claims description 8
- 239000000872 buffer Substances 0.000 claims description 6
- 229960000935 dehydrated alcohol Drugs 0.000 claims description 5
- 239000000203 mixture Substances 0.000 claims description 5
- JLPULHDHAOZNQI-ZTIMHPMXSA-N 1-hexadecanoyl-2-(9Z,12Z-octadecadienoyl)-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCCCCCC\C=C/C\C=C/CCCCC JLPULHDHAOZNQI-ZTIMHPMXSA-N 0.000 claims description 4
- 229930003427 Vitamin E Natural products 0.000 claims description 4
- 235000012000 cholesterol Nutrition 0.000 claims description 4
- WIGCFUFOHFEKBI-UHFFFAOYSA-N gamma-tocopherol Natural products CC(C)CCCC(C)CCCC(C)CCCC1CCC2C(C)C(O)C(C)C(C)C2O1 WIGCFUFOHFEKBI-UHFFFAOYSA-N 0.000 claims description 4
- 239000008347 soybean phospholipid Substances 0.000 claims description 4
- 235000019165 vitamin E Nutrition 0.000 claims description 4
- 229940046009 vitamin E Drugs 0.000 claims description 4
- 239000011709 vitamin E Substances 0.000 claims description 4
- 238000004659 sterilization and disinfection Methods 0.000 claims description 3
- 230000006837 decompression Effects 0.000 claims description 2
- 239000012467 final product Substances 0.000 claims description 2
- 238000012856 packing Methods 0.000 claims description 2
- 229930182558 Sterol Natural products 0.000 abstract 2
- 235000003702 sterols Nutrition 0.000 abstract 2
- 230000000887 hydrating effect Effects 0.000 abstract 1
- 229920000515 polycarbonate Polymers 0.000 abstract 1
- 239000004417 polycarbonate Substances 0.000 abstract 1
- 238000005303 weighing Methods 0.000 abstract 1
- 239000000126 substance Substances 0.000 description 9
- 150000002978 peroxides Chemical class 0.000 description 7
- 238000012360 testing method Methods 0.000 description 7
- 238000003756 stirring Methods 0.000 description 6
- 230000003204 osmotic effect Effects 0.000 description 5
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 4
- 229960004756 ethanol Drugs 0.000 description 4
- 239000002775 capsule Substances 0.000 description 3
- 230000007774 longterm Effects 0.000 description 3
- 239000000047 product Substances 0.000 description 3
- 238000001953 recrystallisation Methods 0.000 description 3
- 238000005070 sampling Methods 0.000 description 3
- 239000008215 water for injection Substances 0.000 description 3
- 238000003556 assay Methods 0.000 description 2
- 230000008859 change Effects 0.000 description 2
- 238000009826 distribution Methods 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 210000001508 eye Anatomy 0.000 description 2
- 238000011835 investigation Methods 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 238000005259 measurement Methods 0.000 description 2
- 239000002245 particle Substances 0.000 description 2
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 2
- 229920000053 polysorbate 80 Polymers 0.000 description 2
- 239000011780 sodium chloride Substances 0.000 description 2
- HRZFUMHJMZEROT-UHFFFAOYSA-L sodium disulfite Chemical compound [Na+].[Na+].[O-]S(=O)S([O-])(=O)=O HRZFUMHJMZEROT-UHFFFAOYSA-L 0.000 description 2
- 235000010262 sodium metabisulphite Nutrition 0.000 description 2
- 238000013112 stability test Methods 0.000 description 2
- 238000010998 test method Methods 0.000 description 2
- 208000002177 Cataract Diseases 0.000 description 1
- 241000283973 Oryctolagus cuniculus Species 0.000 description 1
- 238000013019 agitation Methods 0.000 description 1
- 230000000172 allergic effect Effects 0.000 description 1
- 210000002159 anterior chamber Anatomy 0.000 description 1
- 239000002260 anti-inflammatory agent Substances 0.000 description 1
- 229940124599 anti-inflammatory drug Drugs 0.000 description 1
- 230000003110 anti-inflammatory effect Effects 0.000 description 1
- 208000010668 atopic eczema Diseases 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- 239000008366 buffered solution Substances 0.000 description 1
- 230000003139 buffering effect Effects 0.000 description 1
- 210000005252 bulbus oculi Anatomy 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 239000002085 irritant Substances 0.000 description 1
- 231100000021 irritant Toxicity 0.000 description 1
- 230000007794 irritation Effects 0.000 description 1
- 206010023683 lagophthalmos Diseases 0.000 description 1
- 229940040145 liniment Drugs 0.000 description 1
- 239000000865 liniment Substances 0.000 description 1
- 210000003205 muscle Anatomy 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 239000012047 saturated solution Substances 0.000 description 1
- 238000007789 sealing Methods 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 230000000638 stimulation Effects 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 238000002054 transplantation Methods 0.000 description 1
- 239000003643 water by type Substances 0.000 description 1
Abstract
The invention relates to a preparation method of indometacin liposome eye drops, comprising the steps of: step1, preparing a borate buffer solution with the pH of 6.7-7.3 according to the prescription, filtering and sterilizing for later use; step 2, hydrating compound phosphatide sterol lipid by the borate buffer solution; step 3, weighing indometacin with prescription dosage according to the prescription, and dissolving by a borax solution; step 4, adding the solution obtained in the step 3 into the compound phosphatide sterol lipid hydrated by the buffer solution, and then adjusting the pH value by boric acid; step 5, extruding by a high pressure homogenizer to obtain liposome by sterilizing through a 0.1mu m of polycarbonate microporous filtering membrane; and step 6, carrying out sterile operation and split charging to obtain the finished product.
Description
Technical field:
The present invention relates to a kind of preparation method of liposomal pharmaceutical preparation, particularly a kind of preparation method of Indomethacin liposome eye drops.
Background technology:
Indomethacin is a kind of anti-inflammatory drug, chemical name: 1-(4-chlorobenzene formacyl)-5-methoxyl group-2-Methyl-1H-indole-3-acetic acid, and structural formula is as follows:
The existing dosage form of indomethacin comprises: tablet, capsule, enteric coated capsule, slow releasing capsule, liniment, patch, suppository, eye drop etc.
Indometacin Eye Drops is for ophthalmology cataract intraocular lens post-transplantation, and treatment anterior chamber room sudden strain of a muscle effect is remarkable, and antiinflammatory action is obvious.Again indomethacin is prepared into to the report of eye drop in prior art, as: indomethacin crystallization 0.5g, Borax 0.5g, PVP 2.0g, sodium chloride 0.8g, sodium pyrosulfite 0.1g, tween 80 0.4ml, water for injection adds to 100ml.Preparation method: indomethacin recrystallization: the indomethacin raw material is dissolved in acetone-dehydrated alcohol (5: 1) mixed liquor, makes saturated solution, under agitation (600r/min), splash in 10 times of waters for injection, start slowly, after accelerate gradually, it is cotton-shaped that solution presents a large amount of white, after all adding, continues to stir 5min, with buchner funnel, filter, water for injection rinses 2 times, drains 80 ℃ of oven dry, obtain the indomethacin recrystallization, grind well standby; Get water for injection and heat in water-bath in right amount, add successively tween 80, Borax under stirring, NaCl, sodium pyrosulfite and the PVP solution soak dissolved, until complete molten after, continue to be heated to 80～90 ℃, slowly add indomethacin recrystallization powder, the limit edged is stirred to whole dissolvings, add water to full dose, mix, filter, 100 ℃ of 30min flowing steam sterilizations, aseptic subpackaged, sealing, keep in Dark Place.
Chinese patent 02153385.7 has been described a kind of Indomethacin liposome eye drops, it is by indomethacin, prepare lipid and buffering solution composition for liposome, preparation method adopts lipid and indomethacin dissolve with ethanol, and the indomethacin lipid soln after dissolving is placed on membrane evaporator, removes ethanol, prepare the indomethacin lipid film, neutral buffered solution and indomethacin lipid film are mixed, after the complete aquation of indomethacin lipid film, push with high pressure homogenizer.
The method use ethanol by liposome and indomethacin mixed dissolution, is difficult to remove fully ethanol for solvent in preparing the eye drop process, makes eye drop produce stimulation and the allergic phenomena to eye, is unfavorable for the control of product quality.
In addition, rotary evaporator mostly is glass now, is 50L, 100L to the maximum, and batch volume of production can be restricted.Because used organic solvent, in preparation process, to note at any time Explosion-Proof.
The present invention is according to the distinctive chemical property of indomethacin, in prior art and possess on the basis of pharmaceutic adjuvant composite phospholipid sterin lipid, preparation method to its liposome eye drops has been carried out technological improvement, be more conducive to suitability for industrialized production, and the Indomethacin liposome eye drops steady quality made.
Summary of the invention:
The invention provides a kind of preparation method of Indomethacin liposome eye drops, described Indomethacin liposome eye drops, Indomethacin liposome eye drops prescription composition
Preparation method, step is as follows:
The borate buffer solution that step 1. is 6.7-7.3 by prescription preparation pH, filtration sterilization is standby;
Step 2. is by composite phospholipid sterin lipid borate buffer solution aquation;
The indomethacin that step 3. takes recipe quantity dissolves with borax soln;
Step 4. joins in the composite phospholipid sterin lipids of using the buffer aquation 3, then regulates pH value with boric acid;
High pressure homogenizer extruding for step 5., make liposome through 0.1 μ m Merlon microporous filter membrane degerming.
Under step 6. sterile working, packing and get final product.
Wherein
The compound method of borate buffer solution is as follows: take boric acid 2.5g Borax 0.05g, add water and make to dissolve and be diluted to scale.
The compound method of borax soln is as follows: take the surplus Borax and add water and make to dissolve and be diluted to scale.
The compound method of boric acid solution is as follows: take surplus boric acid and add water and make to dissolve and be diluted to scale.
The compound method of composite phospholipid sterin lipid is as follows:
Formula: soybean phospholipid 165g, cholesterol 35g, vitamin E 0.1g
Preparation method:
1. the soybean phospholipid, cholesterol and the vitamin E that take recipe quantity are put in beaker, with dehydrated alcohol 1500ml, make its dissolving, and mix homogeneously filters.
By lipid soln on membrane evaporator, the decompression remove the dehydrated alcohol film forming after, obtain the lipid block.
Below by test data, advantage of the present invention is described:
The contrast experiment:
Eye drop prepared by the eye drop that the preparation method of the eye drop of describing in employing Chinese patent 02153385.7 obtains and the method for the embodiment of the present invention 4 carries out lagophthalmos eyeball irritation test, and test method is as follows:
Table 1 Indomethacin liposome eye drops and Indometacin Eye Drops are to the rabbit eyes irritant reaction
Result shows, the present invention is better than prior art on zest.
The product stability test:
Test method is as follows:
To be packaged in unit dose package by the Indomethacin liposome eye drops sample of the embodiment of the present invention 4 preparations, 25 ℃ ± 2 ℃ of temperature, under the condition of relative humidity 60% ± 10%, deposit six months, in the 1st, 2,3, June sampling and measuring, under 6 ℃ ± 2 ℃ conditions of temperature, place 12 months, in the 3rd, 6,9, the December sampling and measuring, the investigation project comprises character, pH value, particle diameter and distribution (D thereof
90, mean diameter), related substance, envelop rate, osmotic pressure, peroxide value, assay, measurement result sees the following form.
Table 2 accelerated test examination result
Result shows, the eye drop sample is stored six months under 25 ℃ of conditions of temperature, and pH value, mean diameter, osmotic pressure, envelop rate, content etc. have no significant change; Peroxide value increases to some extent, but up to specification; Related substance increases, but up to specification.
Table 3 long term test examination result
Result shows, sample is stored 12 months under 6 ℃ of conditions of temperature, and pH value, mean diameter, osmotic pressure, envelop rate, content etc. have no significant change; Peroxide value increases to some extent, but up to specification; Related substance increases to some extent, but up to specification, the interpret sample steady quality.
Conclusion: through long-term experiment 12 months (refrigerated condition), result shows, this product steady quality, and indices is all up to specification, and effect duration is decided to be 1 year.
Existing patent sample stability test
The eye drop sample that the preparation method that adopts eye drop in Chinese patent 02153385.7 is obtained is packaged in unit dose package, 25 ℃ ± 2 ℃ of temperature, under the condition of relative humidity 60% ± 10%, deposit six months, under 6 ℃ ± 2 ℃ conditions of temperature, place nine months, sampling and measuring, the investigation project comprises character, pH value, particle diameter and distribution (D thereof
90, mean diameter), related substance, envelop rate, osmotic pressure, peroxide value, assay, measurement result sees the following form.
Table 4
Existing patent sample commercially available back is through accelerated test June (25 ℃ of conditions of temperature), and pH value, mean diameter, osmotic pressure, envelop rate, content are all in the quality standard limits, and peroxide value increases, but up to specification; Related substance 2.92%, exceed prescribed limit.Long term test JIUYUE (6 ℃ of temperature), peroxide value increases, but up to specification; Related substance 2.25%, exceed prescribed limit.
Prepare Indomethacin liposome eye drops by the present invention and compare with the Indomethacin liposome eye drops standby by former patent system, sample stability is better than the latter, wherein peroxide value, the related substance testing result amplitude of variation sample standby much smaller than former patent system.
The specific embodiment:
Further illustrate by the following examples the present invention, but not as limitation of the present invention.
Embodiment 1
One. Indomethacin liposome eye drops prescription (1L) is (0.4ml:2ml)
Two. technique:
(1) preparation borate buffer solution: take boric acid 2.5g Borax 0.05g, add water and make to dissolve and be diluted to scale.
(2) preparation borax soln: take Borax 2.4g and add water and make to dissolve and be diluted to scale.
(3) preparation boric acid solution: take boric acid 11.6g and add water and make to dissolve and be diluted to scale.
(4) composite phospholipid sterin lipid 75g is added to the borate buffer solution aquation;
(5) taking indomethacin 5g adds borax soln and makes to dissolve;
(6) (5) gradation is slowly joined in the composite phospholipid sterin lipid by the buffer aquation, stir.
(7) add again boric acid solution to regulate in right amount pH value;
(8) be crushed to liposome with high pressure homogenizer.
Embodiment 2
One. Indomethacin liposome eye drops prescription (2L) is (0.4ml:2ml)
Two. technique:
(1) preparation borate buffer solution: take boric acid 5g Borax 0.1g, add water and make to dissolve and be diluted to scale.
(2) preparation borax soln: take Borax 4.9g and add water and make to dissolve and be diluted to scale.
(3) preparation boric acid solution: take boric acid 24.4g and add water and make to dissolve and be diluted to scale.
(4) composite phospholipid sterin lipid 150g is added to the borate buffer solution aquation;
(5) taking indomethacin 10g adds borax soln and makes to dissolve;
(6) (5) gradation is slowly joined in the composite phospholipid sterin lipid by the buffer aquation, stir.
(7) add again boric acid solution to regulate in right amount pH value;
(8) be crushed to liposome with high pressure homogenizer.
Embodiment 3
One. Indomethacin liposome eye drops prescription (5L) is (0.4ml:2ml)
Two. technique:
(1) preparation borate buffer solution: take boric acid 12.5g Borax 0.25g, add water and make to dissolve and be diluted to scale.
(2) preparation borax soln: take Borax 12g and add water and make to dissolve and be diluted to scale.
(3) preparation boric acid solution: take boric acid 59g and add water and make to dissolve and be diluted to scale.
(4) composite phospholipid sterin lipid 375g is added to the borate buffer solution aquation;
(5) taking indomethacin 25g adds borax soln and makes to dissolve;
(6) (5) gradation is slowly joined in the composite phospholipid sterin lipid by the buffer aquation, stir.
(7) add again boric acid solution to regulate in right amount pH value;
(8) be crushed to liposome with high pressure homogenizer.
Embodiment 4
One. Indomethacin liposome eye drops prescription (10L) is (0.4ml:2ml)
Two. technique:
(1) preparation borate buffer solution: take boric acid 25g Borax 0.5g, add water and make to dissolve and be diluted to scale.
(2) preparation borax soln: take Borax 24g and add water and make to dissolve and be diluted to scale.
(3) preparation boric acid solution: take boric acid 117.8g and add water and make to dissolve and be diluted to scale.
(4) composite phospholipid sterin lipid 756g is added to the borate buffer solution aquation.
(5) taking indomethacin 50g adds borax soln and makes to dissolve.
(6) (5) gradation is slowly joined in the composite phospholipid sterin lipid by the buffer aquation, stir.
(7) add again boric acid solution to regulate in right amount pH value;
(8) be crushed to liposome with high pressure homogenizer.
Claims (1)
1. the preparation method of an Indomethacin liposome eye drops, is characterized in that,
The formula of eye drop consists of:
Indomethacin 5g
Composite phospholipid sterin lipid 75g
Borax 2.5g
Boric acid 14.25g
Water adds to 1000ml
Wherein, the compound method of composite phospholipid sterin lipid is as follows:
Formula: soybean phospholipid 165g, cholesterol 35g, vitamin E 0.1g
Preparation method:
1) soybean phospholipid, cholesterol and the vitamin E that take recipe quantity are put in beaker, with dehydrated alcohol 1500ml, make its dissolving, and mix homogeneously filters;
2) by lipid soln on membrane evaporator, the decompression remove the dehydrated alcohol film forming after, obtain the lipid block;
The preparation method of described eye drop, step is as follows:
The borate buffer solution that step 1. preparation pH is 6.7-7.3, filtration sterilization is standby;
Step 2. is by composite phospholipid sterin lipid borate buffer solution aquation;
The indomethacin that step 3. takes recipe quantity dissolves with borax soln;
Step 4. joins step 3 in the composite phospholipid sterin lipid by the buffer aquation, then regulates pH value with boric acid;
High pressure homogenizer extruding for step 5., make liposome through 0.1 μ m Merlon microporous filter membrane degerming;
Under step 6. sterile working, packing and get final product;
Wherein, the compound method of borate buffer solution is as follows: take boric acid 2.5g, Borax 0.05g, add water and make to dissolve and be diluted to scale;
Wherein, the compound method of borax soln is as follows: take the surplus Borax and add water and make to dissolve and be diluted to scale;
Wherein, the compound method of boric acid solution is as follows: take surplus boric acid and add water and make to dissolve and be diluted to scale.
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2012100720535A CN102631318B (en) | 2012-03-19 | 2012-03-19 | Preparation method of indometacin liposome eye drops |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2012100720535A CN102631318B (en) | 2012-03-19 | 2012-03-19 | Preparation method of indometacin liposome eye drops |
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| CN102631318B true CN102631318B (en) | 2013-12-11 |
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Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1416811A (en) * | 2002-11-29 | 2003-05-14 | 孙仁俊 | Indomethacin liposome eye drops |
| CN1517089A (en) * | 2003-01-15 | 2004-08-04 | 珊 赵 | Indometacin eyedrops |
| CN1852702A (en) * | 2003-07-31 | 2006-10-25 | 得克萨斯大学体系董事会 | Sterile preparations of phospholipids and anti-inflammatory pharmaceuticals and methods for making and using same |
| CN101095695A (en) * | 2007-08-10 | 2008-01-02 | 孙猛 | Liposome artificial tear eye drops |
-
2012
- 2012-03-19 CN CN2012100720535A patent/CN102631318B/en active Active
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1416811A (en) * | 2002-11-29 | 2003-05-14 | 孙仁俊 | Indomethacin liposome eye drops |
| CN1517089A (en) * | 2003-01-15 | 2004-08-04 | 珊 赵 | Indometacin eyedrops |
| CN1852702A (en) * | 2003-07-31 | 2006-10-25 | 得克萨斯大学体系董事会 | Sterile preparations of phospholipids and anti-inflammatory pharmaceuticals and methods for making and using same |
| CN101095695A (en) * | 2007-08-10 | 2008-01-02 | 孙猛 | Liposome artificial tear eye drops |
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| Publication number | Publication date |
|---|---|
| CN102631318A (en) | 2012-08-15 |
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Owner name: SUN XIANG Effective date: 20131010 |
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Effective date of registration: 20131010 Address after: Jin Feng Road Jinding Industrial Park in Guangdong province Zhuhai City Xiangzhou District 519085 No. 29 Applicant after: Sun Meng Applicant after: Sun Xiang Address before: Jin Feng Road Jinding Industrial Park in Guangdong province Zhuhai City Xiangzhou District 519085 No. 29 Applicant before: Sun Meng |
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Effective date of registration: 20180205 Address after: Jin Feng Road Jinding Industrial Park Xiangzhou District 519080 Guangdong city of Zhuhai Province Co-patentee after: Sun Xiang Patentee after: Sun Meng Co-patentee after: Dou Qifeng Address before: Jin Feng Road Jinding Industrial Park in Guangdong province Zhuhai City Xiangzhou District 519085 No. 29 Co-patentee before: Sun Xiang Patentee before: Sun Meng |
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Effective date of registration: 20180625 Address after: 528437 Zhongshan, Guangdong Torch Development Zone, 1 Lane first, two, 201 rooms. Patentee after: Zhongshan storage Hao Li Po Pharmaceutical Technology Co., Ltd. Address before: 519080 Jinfeng West Road, Jinding Industrial Park, Xiangzhou District, Zhuhai, Guangdong, China Co-patentee before: Sun Xiang Patentee before: Sun Meng |
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