CN102940886B - Biological barrier penetrating agent and preparation method thereof - Google Patents
Biological barrier penetrating agent and preparation method thereof Download PDFInfo
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- CN102940886B CN102940886B CN201210541283.1A CN201210541283A CN102940886B CN 102940886 B CN102940886 B CN 102940886B CN 201210541283 A CN201210541283 A CN 201210541283A CN 102940886 B CN102940886 B CN 102940886B
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- 230000004888 barrier function Effects 0.000 title claims abstract description 32
- 230000000149 penetrating effect Effects 0.000 title claims abstract description 19
- 238000002360 preparation method Methods 0.000 title claims abstract description 16
- 239000003795 chemical substances by application Substances 0.000 claims abstract description 18
- -1 fatty acid salt Chemical class 0.000 claims abstract description 10
- 239000003381 stabilizer Substances 0.000 claims abstract description 9
- 229920003169 water-soluble polymer Polymers 0.000 claims abstract description 9
- 238000003756 stirring Methods 0.000 claims description 12
- 239000004615 ingredient Substances 0.000 claims description 11
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 10
- 239000008187 granular material Substances 0.000 claims description 10
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 claims description 9
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical group CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 8
- 230000002209 hydrophobic effect Effects 0.000 claims description 7
- 239000000344 soap Substances 0.000 claims description 7
- 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 6
- 229940079322 interferon Drugs 0.000 claims description 5
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 claims description 4
- 102000004269 Granulocyte Colony-Stimulating Factor Human genes 0.000 claims description 4
- 108010017080 Granulocyte Colony-Stimulating Factor Proteins 0.000 claims description 4
- 238000001035 drying Methods 0.000 claims description 4
- 229920000036 polyvinylpyrrolidone Polymers 0.000 claims description 4
- 239000001267 polyvinylpyrrolidone Substances 0.000 claims description 4
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 claims description 4
- WXMKPNITSTVMEF-UHFFFAOYSA-M sodium benzoate Chemical group [Na+].[O-]C(=O)C1=CC=CC=C1 WXMKPNITSTVMEF-UHFFFAOYSA-M 0.000 claims description 4
- 239000004299 sodium benzoate Substances 0.000 claims description 4
- 235000010234 sodium benzoate Nutrition 0.000 claims description 4
- BTURAGWYSMTVOW-UHFFFAOYSA-M sodium dodecanoate Chemical compound [Na+].CCCCCCCCCCCC([O-])=O BTURAGWYSMTVOW-UHFFFAOYSA-M 0.000 claims description 4
- 229940082004 sodium laurate Drugs 0.000 claims description 4
- 239000000600 sorbitol Substances 0.000 claims description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 4
- 102000007644 Colony-Stimulating Factors Human genes 0.000 claims description 3
- 108010071942 Colony-Stimulating Factors Proteins 0.000 claims description 3
- 102000004190 Enzymes Human genes 0.000 claims description 3
- 108090000790 Enzymes Proteins 0.000 claims description 3
- 102000014150 Interferons Human genes 0.000 claims description 3
- 108010050904 Interferons Proteins 0.000 claims description 3
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical class CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 claims description 3
- RVGRUAULSDPKGF-UHFFFAOYSA-N Poloxamer Chemical compound C1CO1.CC1CO1 RVGRUAULSDPKGF-UHFFFAOYSA-N 0.000 claims description 3
- 239000002202 Polyethylene glycol Substances 0.000 claims description 3
- 239000004372 Polyvinyl alcohol Substances 0.000 claims description 3
- 239000002775 capsule Substances 0.000 claims description 3
- 235000012000 cholesterol Nutrition 0.000 claims description 3
- CTTKODQWVMTOPW-UHFFFAOYSA-N decanoic acid;sodium Chemical compound [Na].CCCCCCCCCC(O)=O CTTKODQWVMTOPW-UHFFFAOYSA-N 0.000 claims description 3
- 150000002191 fatty alcohols Chemical class 0.000 claims description 3
- 210000003714 granulocyte Anatomy 0.000 claims description 3
- 239000002955 immunomodulating agent Substances 0.000 claims description 3
- 230000002584 immunomodulator Effects 0.000 claims description 3
- 229940121354 immunomodulator Drugs 0.000 claims description 3
- 229960000502 poloxamer Drugs 0.000 claims description 3
- 229920001983 poloxamer Polymers 0.000 claims description 3
- 229920001223 polyethylene glycol Polymers 0.000 claims description 3
- 229920002451 polyvinyl alcohol Polymers 0.000 claims description 3
- 229960005480 sodium caprylate Drugs 0.000 claims description 3
- BYKRNSHANADUFY-UHFFFAOYSA-M sodium octanoate Chemical compound [Na+].CCCCCCCC([O-])=O BYKRNSHANADUFY-UHFFFAOYSA-M 0.000 claims description 3
- 239000003826 tablet Substances 0.000 claims description 3
- UFTFJSFQGQCHQW-UHFFFAOYSA-N triformin Chemical compound O=COCC(OC=O)COC=O UFTFJSFQGQCHQW-UHFFFAOYSA-N 0.000 claims description 3
- 239000003814 drug Substances 0.000 abstract description 26
- 210000004369 blood Anatomy 0.000 abstract description 21
- 239000008280 blood Substances 0.000 abstract description 21
- 230000000694 effects Effects 0.000 abstract description 9
- 235000014113 dietary fatty acids Nutrition 0.000 abstract description 6
- 239000000194 fatty acid Substances 0.000 abstract description 6
- 229930195729 fatty acid Natural products 0.000 abstract description 6
- 239000012736 aqueous medium Substances 0.000 abstract 2
- 239000002609 medium Substances 0.000 abstract 2
- 239000000969 carrier Substances 0.000 abstract 1
- 230000035699 permeability Effects 0.000 abstract 1
- 229940079593 drug Drugs 0.000 description 13
- 239000000203 mixture Substances 0.000 description 9
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical group OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 6
- 230000035515 penetration Effects 0.000 description 6
- 201000010099 disease Diseases 0.000 description 5
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 5
- 238000009472 formulation Methods 0.000 description 5
- QYSXJUFSXHHAJI-XFEUOLMDSA-N Vitamin D3 Natural products C1(/[C@@H]2CC[C@@H]([C@]2(CCC1)C)[C@H](C)CCCC(C)C)=C/C=C1\C[C@@H](O)CCC1=C QYSXJUFSXHHAJI-XFEUOLMDSA-N 0.000 description 4
- 239000011647 vitamin D3 Substances 0.000 description 4
- QYSXJUFSXHHAJI-YRZJJWOYSA-N vitamin D3 Chemical compound C1(/[C@@H]2CC[C@@H]([C@]2(CCC1)C)[C@H](C)CCCC(C)C)=C\C=C1\C[C@@H](O)CCC1=C QYSXJUFSXHHAJI-YRZJJWOYSA-N 0.000 description 4
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- 229940021056 vitamin d3 Drugs 0.000 description 4
- 241000699670 Mus sp. Species 0.000 description 3
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 2
- 206010028980 Neoplasm Diseases 0.000 description 2
- 150000001841 cholesterols Chemical class 0.000 description 2
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- 235000010446 mineral oil Nutrition 0.000 description 2
- 238000002156 mixing Methods 0.000 description 2
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 2
- 150000003505 terpenes Chemical class 0.000 description 2
- 239000001993 wax Substances 0.000 description 2
- 229920001353 Dextrin Polymers 0.000 description 1
- 239000004375 Dextrin Substances 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- 201000003793 Myelodysplastic syndrome Diseases 0.000 description 1
- 208000001132 Osteoporosis Diseases 0.000 description 1
- 210000001552 airway epithelial cell Anatomy 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- 230000008499 blood brain barrier function Effects 0.000 description 1
- 210000001218 blood-brain barrier Anatomy 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- 210000001185 bone marrow Anatomy 0.000 description 1
- 210000004556 brain Anatomy 0.000 description 1
- 201000011510 cancer Diseases 0.000 description 1
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- 238000002512 chemotherapy Methods 0.000 description 1
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- 235000019425 dextrin Nutrition 0.000 description 1
- 230000000857 drug effect Effects 0.000 description 1
- 210000002615 epidermis Anatomy 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 230000001900 immune effect Effects 0.000 description 1
- 210000000987 immune system Anatomy 0.000 description 1
- 210000002490 intestinal epithelial cell Anatomy 0.000 description 1
- 201000002364 leukopenia Diseases 0.000 description 1
- 231100001022 leukopenia Toxicity 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 238000012423 maintenance Methods 0.000 description 1
- 230000007257 malfunction Effects 0.000 description 1
- 230000036210 malignancy Effects 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 239000008213 purified water Substances 0.000 description 1
- 238000001959 radiotherapy Methods 0.000 description 1
- 210000003491 skin Anatomy 0.000 description 1
- 230000004083 survival effect Effects 0.000 description 1
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Abstract
The invention relates to a biological barrier penetrating agent. The biological barrier penetrating agent is characterized by comprising the following components in parts by weight: 3-7 parts of medical components, 1-5 parts of fatty acid salt, 1-5 parts of an aqueous medium, 13-17 parts of a water-soluble medium, 13-17 parts of a non-ionic stabilizing agent and 8-12 parts of water-soluble polymer. According to the biological barrier penetrating agent, the medical components are sufficiently mixed with the fatty acid salt, the aqueous medium, the water-soluble medium, the non-ionic stabilizing agent and the water-soluble polymer to prepare various preparations with biologically acceptable carriers; and compared with the existing used preparations, a test result shows that a biological barrier can be penetrated in short time; a blood medicine peak value and a blood medicine concentration are greatly improved and the time for reaching to a blood medicine peak concentration is greatly shortened; and the permeability and the effect of the medical components are effectively improved.
Description
Technical field
The invention belongs to
especially a kind of biological barrier penetrating agent and preparation method thereof.
Background technology
Biological barrier is a whole set of maintenance body normal activity that biology grows up in long-term evolution, the mechanism stoping or resist alien material; it plays very important effect in the survival and development of protection biology; along with biology by rudimentary to senior continuous evolution, biological barrier is also perfect from simple to complex and constantly.As: the interface, space of cell is exactly biological barrier the most original together, in plant, biological barrier shows as the epidermis that plant exposes aerial stem, leaf, flower etc., in higher mammal, it is more perfect that biological barrier develops, and except skin, also has immune system, especially, in the vitals such as heart, brain, biological barrier is more complicated, accurate.
But biological barrier is while protection body; also can the medicine be used for the treatment of be stopped; especially some dense biological barriers; as: intestinal epithelial cell, airway epithelial cell, vascular endothelial cell, blood brain barrier etc.; it can cause the Penetration ration of medicine to reduce; thus drug effect is deteriorated, although there are some assistant medicaments can increase the Penetration ration of medicine, effect is not very stable.
Summary of the invention
The object of the invention is to overcome the deficiencies in the prior art, scientific formulation is provided, effectively improve a kind of biological barrier penetrating agent of drug permeation rate.
The technical scheme that the present invention takes is:
A kind of biological barrier penetrating agent, is characterized in that: comprise the following component mixed by weight:
And described ingredient is interferon, immunomodulator, soluble recepter, enzyme, antibody, granulocyte colony-stimulating factor or Granulocyte microphage colony stimulating factor.
And described soap is the mixture of one or more in sodium caprylate, sodium capric acid, sodium laurate.
And described hydrophobic medium is the mixture of one or more in mineral oil, wax, fatty acid, diglyceride, triglyceride, ether, terpenoid, cholesterol, cholesterol derivative or sodium benzoate.
And described water-soluble medium is methanol, ethanol, propanol, isopropyl alcohol or butanols.
And described non-ionic stabilizer is polyethylene glycol fatty alcohol ether, poloxamer, anhydrous sorbitol or fatty acid ester.
And described water-soluble polymer is polyvinylpyrrolidone or polyvinyl alcohol.
Another object of the present invention is to provide a kind of by biological barrier penetrating agent and tablet, granule or capsule that biology, acceptable carrier was made.
Another object of the present invention is to provide a kind of preparation method of biological barrier penetrating agent, it is characterized in that: comprise the following steps:
(1), by water boil, add non-ionic stabilizer, stir make it dissolve, continue to be heated to 100 DEG C, filter, be naturally placed to 60 ~ 70 DEG C for subsequent use;
(2) ingredient, hydrophobic medium, water-soluble polymer and carrier are positioned in granulator and are dry mixed 15 minutes;
(3) soap is added in water-soluble medium, stir and make it dissolve;
(4) (1), (2) step is put into together with product (3) granulator to stir 10 minutes, namely obtained granule obtains finished product after drying.
Advantage of the present invention and good effect are:
In the present invention, ingredient is fully mixed with soap, hydrophobic medium, water-soluble medium, non-ionic stabilizer and water-soluble polymer, then various preparation is made with acceptable carrier biology, by comparing with the preparation of existing use, result of the test display can pass through biological barrier in the short time, blood medicine peak value and blood drug level all significantly improve, and reach the blood peak concentration of drug time significantly to reduce, and effectively raise Penetration ration and the effect of ingredient.
Detailed description of the invention
Below in conjunction with embodiment, the present invention is further described, and following embodiment is illustrative, is not determinate, can not limit protection scope of the present invention with following embodiment.
A kind of biological barrier penetrating agent, innovation of the present invention is: comprise the following component mixed by weight:
Wherein, ingredient is interferon, immunomodulator, soluble recepter, enzyme, antibody, granulocyte colony-stimulating factor or Granulocyte microphage colony stimulating factor.Soap is the mixture of one or more in sodium caprylate, sodium capric acid, sodium laurate.Hydrophobic medium is the mixture of one or more in mineral oil, wax, fatty acid, diglyceride, triglyceride, ether, terpenoid, cholesterol, cholesterol derivative or sodium benzoate.Water-soluble medium is methanol, ethanol, propanol, isopropyl alcohol or butanols.Non-ionic stabilizer is polyethylene glycol fatty alcohol ether, poloxamer, anhydrous sorbitol or fatty acid ester.Water-soluble polymer is polyvinylpyrrolidone or polyvinyl alcohol.
Above-mentioned biological barrier penetrating agent can with the tablet that biology, acceptable carrier was made, granule or capsule.
The preparation method of above-mentioned biological barrier penetrating agent, comprises the following steps:
(1), by water boil, add non-ionic stabilizer, stir make it dissolve, continue to be heated to 100 DEG C, filter, be naturally placed to 60 ~ 70 DEG C for subsequent use;
(2) ingredient, hydrophobic medium, water-soluble polymer and carrier are positioned in granulator and are dry mixed 15 minutes;
(3) soap is added in water-soluble medium, stir and make it dissolve;
(4) (1), (2) step is put into together with product (3) granulator to stir 10 minutes, then granulate, after drying, namely obtain finished product.
Embodiment 1
Treatment disease: cholecalciferol, health invigorating in osteoporosis, added body
Weigh above-mentioned each component for subsequent use, preparation method is as follows:
(1) get 10 milliliters of purified water, after boiling, add anhydrous sorbitol, stir make it dissolve, continue to be heated to 100 DEG C, filter, be naturally placed to 60 ~ 70 DEG C for subsequent use;
(2) cholecalciferol, sodium benzoate, polyvinylpyrrolidone and dextrin are positioned in high-speed mixing granulating machine and are dry mixed 15 minutes;
(3) sodium laurate is added in 15 milliliters of ethanol, stir and make it dissolve;
(4) (1), (2) step is put into together with product (3) high-speed mixing granulating machine to stir 10 minutes, open chipper simultaneously and granulate, the granule made should be complete, even;
(5) step product (4) puts into HighefficientFluidbeddrier inner drying, and baking temperature is 55 ~ 65 DEG C, and the time is 50 minutes;
(6) step product (5) carries out granulate with 12 mesh sieves by collator rule of operation;
(7) the granule after arranging carries out subpackage.
Embodiment 2
Treatment disease: for the treatment of Several Kinds of Malignancy, the control of viral disease.
Weigh above-mentioned each component for subsequent use, preparation method is identical with embodiment 1.
Embodiment 3
Treatment disease: the leukopenia caused by prevention and therapy tumor Radiotherapy chemotherapy
Disease, bone marrow hematogenesis malfunction and myelodysplastic syndrome.
Weigh above-mentioned each component for subsequent use, preparation method is identical with embodiment 1.
The finished product that above-mentioned three embodiments obtain carries out following test:
1. embodiment 1
Finished product obtained for embodiment 1 is pressed identical condition feeding mice with the cholecalciferol of conventional general formulation, and then measure, result is as shown in table 1:
| Blood medicine peak value | 4h blood drug level | Reach blood peak concentration of drug time (h) | |
| General formulation cholecalciferol | 14.87ug/ml | 14.28 | 4.25 |
| Embodiment 1 | 21.24ug/ml | 18.46 | 0.48 |
Table 1: the result of the test of embodiment 1
From above-mentioned table 1, ingredient is added after various component makes biological barrier penetrating agent, and blood medicine peak value and blood drug level all significantly improve, and reaches the blood peak concentration of drug time significantly to reduce, visible said preparation can pass through mucocutaneous barrier in the short time, improve Penetration ration and the effect of administration.
2. embodiment 2
Finished product obtained for embodiment 2 is pressed identical condition feeding mice with the a-interferon of conventional general formulation, and then measure, result is as shown in table 2:
| Blood medicine peak value | 4h blood drug level | Reach blood peak concentration of drug time (h) | |
| Common a-interferon | 21.38ug/ml | 17.78 | 5.91 |
| Embodiment 2 | 33.17ug/ml | 26.41 | 0.72 |
Table 2: the result of the test of embodiment 2
From above-mentioned table 2, ingredient is added after various component makes biological barrier penetrating agent, and blood medicine peak value and blood drug level all significantly improve, and reaches the blood peak concentration of drug time significantly to reduce, visible said preparation can pass through after birth barrier in the short time, improve Penetration ration and the effect of administration.
3. embodiment 3
Finished product obtained for embodiment 3 is pressed identical condition feeding mice with the granulocyte colony-stimulating factor of conventional general formulation, and then measure, result is as shown in table 3:
Table 3: the result of the test of embodiment 3
From above-mentioned table 3, ingredient is added after various component makes biological barrier penetrating agent, and blood medicine peak value and blood drug level all significantly improve, and reaches the blood peak concentration of drug time significantly to reduce, visible said preparation can pass through immunologic barrier in the short time, improves Penetration ration and the effect of administration.
Claims (2)
1. a biological barrier penetrating agent, is characterized in that: comprise the following component mixed by weight:
Described soap is sodium caprylate, sodium capric acid or sodium laurate;
Described hydrophobic medium is sodium benzoate, triglyceride or cholesterol;
Described water-soluble medium is ethanol, butanols or isopropyl alcohol;
Described non-ionic stabilizer is polyethylene glycol fatty alcohol ether, poloxamer or anhydrous sorbitol;
Described water-soluble polymer is polyvinylpyrrolidone or polyvinyl alcohol;
Described ingredient is interferon, immunomodulator, soluble recepter, enzyme, antibody, granulocyte colony-stimulating factor or Granulocyte microphage colony stimulating factor;
The preparation method of described biological barrier penetrating agent comprises the following steps:
(1), by water boil, add non-ionic stabilizer, stir make it dissolve, continue to be heated to 100 DEG C, filter, be naturally placed to 60 ~ 70 DEG C for subsequent use;
(2) ingredient, hydrophobic medium, water-soluble polymer and carrier are positioned in granulator and are dry mixed 15 minutes;
(3) soap is added in water-soluble medium, stir and make it dissolve;
(4) (1), (2) step is put into together with product (3) granulator to stir 10 minutes, namely obtained granule obtains finished product after drying.
2. one kind by biological barrier penetrating agent according to claim 1 and tablet, granule or capsule that biology, acceptable carrier was made.
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| CN201210541283.1A CN102940886B (en) | 2012-12-13 | 2012-12-13 | Biological barrier penetrating agent and preparation method thereof |
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| CN201210541283.1A CN102940886B (en) | 2012-12-13 | 2012-12-13 | Biological barrier penetrating agent and preparation method thereof |
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| CN102940886A CN102940886A (en) | 2013-02-27 |
| CN102940886B true CN102940886B (en) | 2015-02-18 |
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| WO2017084683A1 (en) | 2015-11-20 | 2017-05-26 | Hepa Wash Gmbh | Method for extracorporeal lung support |
| WO2017084682A1 (en) | 2015-11-20 | 2017-05-26 | Hepa Wash Gmbh | Method for extracorporeal carbon dioxide removal |
| CA3017435A1 (en) | 2016-03-14 | 2017-09-21 | Hepa Wash Gmbh | Systems or apparatuses and methods for performing dialysis |
| US20210100941A1 (en) * | 2017-03-28 | 2021-04-08 | Advitos Gmbh | Compositions and methods for regenerating carrier protein-containing multiple pass albumin dialysis fluid |
| KR20200011461A (en) | 2017-05-22 | 2020-02-03 | 아드비토스 게엠베하 | Carbon Dioxide Removal Method and System |
Citations (1)
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|---|---|---|---|---|
| CN101084016A (en) * | 2004-04-15 | 2007-12-05 | 克艾思马有限公司 | Compositions capable of facilitating penetration across a biological barrier |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN101084016A (en) * | 2004-04-15 | 2007-12-05 | 克艾思马有限公司 | Compositions capable of facilitating penetration across a biological barrier |
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Effective date of registration: 20200701 Address after: Unit 516, block a, No. 3, Huatian Road, Huayuan Industrial Zone, Binhai New Area, Tianjin Patentee after: Tianjin aotailai Biotechnology Co., Ltd Address before: 300383 No. two branch road, Shengli Zhuang Industrial Park, Xiqing District, Tianjin, 27 Patentee before: S & E Animal Pharmaceutical (TianJin) Co.,Ltd. |
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