CN104447683A - Stable Bilastine compound - Google Patents
Stable Bilastine compound Download PDFInfo
- Publication number
- CN104447683A CN104447683A CN201310413289.5A CN201310413289A CN104447683A CN 104447683 A CN104447683 A CN 104447683A CN 201310413289 A CN201310413289 A CN 201310413289A CN 104447683 A CN104447683 A CN 104447683A
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- China
- Prior art keywords
- bilastine
- hydrate
- crystal
- composition
- preparation
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- 229960004314 bilastine Drugs 0.000 title claims abstract description 42
- -1 Bilastine compound Chemical class 0.000 title description 6
- ACCMWZWAEFYUGZ-UHFFFAOYSA-N bilastine Chemical compound N=1C2=CC=CC=C2N(CCOCC)C=1C(CC1)CCN1CCC1=CC=C(C(C)(C)C(O)=O)C=C1 ACCMWZWAEFYUGZ-UHFFFAOYSA-N 0.000 claims abstract description 36
- 239000013078 crystal Substances 0.000 claims abstract description 16
- 238000002360 preparation method Methods 0.000 claims abstract description 12
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 10
- 239000003814 drug Substances 0.000 claims abstract description 7
- 238000000034 method Methods 0.000 claims description 11
- 208000024780 Urticaria Diseases 0.000 claims description 8
- 239000000203 mixture Substances 0.000 claims description 8
- 238000004519 manufacturing process Methods 0.000 claims description 6
- 206010010744 Conjunctivitis allergic Diseases 0.000 claims description 4
- 201000010435 allergic urticaria Diseases 0.000 claims description 4
- 238000009413 insulation Methods 0.000 claims description 4
- RFQIWHDNNZFRBL-UHFFFAOYSA-N acetic acid;ethanol;hydrate Chemical compound O.CCO.CC(O)=O RFQIWHDNNZFRBL-UHFFFAOYSA-N 0.000 claims description 3
- 238000002425 crystallisation Methods 0.000 claims description 3
- 230000008025 crystallization Effects 0.000 claims description 3
- 238000001035 drying Methods 0.000 claims description 3
- 239000011259 mixed solution Substances 0.000 claims description 3
- 239000003937 drug carrier Substances 0.000 claims description 2
- 238000005259 measurement Methods 0.000 claims description 2
- 239000000243 solution Substances 0.000 claims description 2
- 230000003595 spectral effect Effects 0.000 claims description 2
- 229910016523 CuKa Inorganic materials 0.000 claims 1
- 238000001816 cooling Methods 0.000 claims 1
- 239000000843 powder Substances 0.000 claims 1
- 238000010521 absorption reaction Methods 0.000 abstract description 2
- 229940079593 drug Drugs 0.000 abstract 1
- 230000004584 weight gain Effects 0.000 abstract 1
- 235000019786 weight gain Nutrition 0.000 abstract 1
- 150000001875 compounds Chemical class 0.000 description 7
- 238000005516 engineering process Methods 0.000 description 7
- 239000000126 substance Substances 0.000 description 6
- 230000000694 effects Effects 0.000 description 5
- 239000003981 vehicle Substances 0.000 description 5
- 239000000739 antihistaminic agent Substances 0.000 description 3
- 239000000463 material Substances 0.000 description 3
- 239000008194 pharmaceutical composition Substances 0.000 description 3
- 206010010741 Conjunctivitis Diseases 0.000 description 2
- NTYJJOPFIAHURM-UHFFFAOYSA-N Histamine Chemical compound NCCC1=CN=CN1 NTYJJOPFIAHURM-UHFFFAOYSA-N 0.000 description 2
- 229920000168 Microcrystalline cellulose Polymers 0.000 description 2
- 230000000172 allergic effect Effects 0.000 description 2
- 230000001387 anti-histamine Effects 0.000 description 2
- 208000010668 atopic eczema Diseases 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 238000006243 chemical reaction Methods 0.000 description 2
- 239000012153 distilled water Substances 0.000 description 2
- 239000012535 impurity Substances 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- 235000019813 microcrystalline cellulose Nutrition 0.000 description 2
- 239000008108 microcrystalline cellulose Substances 0.000 description 2
- 229940016286 microcrystalline cellulose Drugs 0.000 description 2
- 238000002156 mixing Methods 0.000 description 2
- 230000003287 optical effect Effects 0.000 description 2
- 239000000825 pharmaceutical preparation Substances 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- 238000003860 storage Methods 0.000 description 2
- 208000024891 symptom Diseases 0.000 description 2
- 238000002636 symptomatic treatment Methods 0.000 description 2
- 206010067484 Adverse reaction Diseases 0.000 description 1
- 108090000312 Calcium Channels Proteins 0.000 description 1
- 102000003922 Calcium Channels Human genes 0.000 description 1
- 102000016289 Cell Adhesion Molecules Human genes 0.000 description 1
- 108010067225 Cell Adhesion Molecules Proteins 0.000 description 1
- 102000019034 Chemokines Human genes 0.000 description 1
- 108010012236 Chemokines Proteins 0.000 description 1
- 229910002483 Cu Ka Inorganic materials 0.000 description 1
- 102000002004 Cytochrome P-450 Enzyme System Human genes 0.000 description 1
- 108010015742 Cytochrome P-450 Enzyme System Proteins 0.000 description 1
- 102000004127 Cytokines Human genes 0.000 description 1
- 108090000695 Cytokines Proteins 0.000 description 1
- 206010013710 Drug interaction Diseases 0.000 description 1
- 102000003834 Histamine H1 Receptors Human genes 0.000 description 1
- 108090000110 Histamine H1 Receptors Proteins 0.000 description 1
- 108010044467 Isoenzymes Proteins 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 230000006838 adverse reaction Effects 0.000 description 1
- 230000009285 allergic inflammation Effects 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 239000005557 antagonist Substances 0.000 description 1
- 229940124623 antihistamine drug Drugs 0.000 description 1
- 229940125715 antihistaminic agent Drugs 0.000 description 1
- 125000005605 benzo group Chemical group 0.000 description 1
- 230000000747 cardiac effect Effects 0.000 description 1
- 210000003169 central nervous system Anatomy 0.000 description 1
- 238000001311 chemical methods and process Methods 0.000 description 1
- 238000012790 confirmation Methods 0.000 description 1
- 239000000356 contaminant Substances 0.000 description 1
- 238000003745 diagnosis Methods 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 238000004896 high resolution mass spectrometry Methods 0.000 description 1
- 229960001340 histamine Drugs 0.000 description 1
- 239000000938 histamine H1 antagonist Substances 0.000 description 1
- 238000005286 illumination Methods 0.000 description 1
- 238000007689 inspection Methods 0.000 description 1
- 238000011835 investigation Methods 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- 150000002894 organic compounds Chemical class 0.000 description 1
- 230000002093 peripheral effect Effects 0.000 description 1
- 230000002085 persistent effect Effects 0.000 description 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
- 238000011020 pilot scale process Methods 0.000 description 1
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- 238000000634 powder X-ray diffraction Methods 0.000 description 1
- 230000000770 proinflammatory effect Effects 0.000 description 1
- 238000000425 proton nuclear magnetic resonance spectrum Methods 0.000 description 1
- 238000007670 refining Methods 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 229940079832 sodium starch glycolate Drugs 0.000 description 1
- 229920003109 sodium starch glycolate Polymers 0.000 description 1
- 239000008109 sodium starch glycolate Substances 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 238000013112 stability test Methods 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Abstract
Belonging to the technical field of medicines, the invention in particular relates to a Bilastine hydrate and a preparation method thereof. The Bilastine hydrate obtained by the invention contains crystal water, and has the advantages of: high purity, good stability, and non-obvious moisture absorption weight gain under a high humidity condition.
Description
Technical field
The invention belongs to medical art, be specifically related to bilastine hydrate and preparation method thereof, the invention still further relates to the composition using this hydrate, and manufacture the application in treatment allergic rhinoconjunctivitis and urticaria medicine.
Background technology
Bilastine (Bilastine), be researched and developed by FAES drugmaker of Spain, in September, 2010 goes on the market in Germany's approval, trade(brand)name: Bilaxten.This product is applicable to the symptomatic treatment of seasonality or perennial allergic nose conjunctivitis and urticaria clinically.This medicine determined curative effect, dosage is little, and side effect is lower.
The medicament categories that current China is used for the treatment of rhinallergosis and urticaria is various, bilastine is as oral s-generation antihistamine drug, it is a kind of long-acting, selectivity H1 receptor antagonist, can efficiently, persistent, specific antagonist peripheral H1-receptor, lower the expression of pro-inflammatory cytokine, cell adhesion molecules and chemokine, affect the activity of calcium channel and reduce medium release, thus reducing allergic inflammation reaction, alleviating the various symptoms of histamine mediation.Compared with other two generation antihistaminics, the curative effect in treatment rhinallergosis and urticaria and the similar basis of other antihistaminic in two generation, its Therapy characteristics is: 1. onset time is shorter, and the time length is longer; 2. good security and tolerance, less and cardiac toxic is lower to central nervous system effects, long term administration adverse reaction rate is low and symptom is relatively slight; 3. do not observe to exist with Cytochrome P450 isozyme and interact, not occurring the drug interaction relevant to metabolism, when determining special population administration, need not dosage be adjusted.Clinically, bilastine is applicable to the symptomatic treatment of seasonality or perennial allergic nose conjunctivitis and urticaria.
This product chemistry 2-[4-(2-(4-(1-(2-ethoxyethyl group) benzo Dimazole-2-base) piperidines-l-base) ethyl) phenyl]-2-dimethyl acetic acid by name, molecular formula: C28H37N3O3, molecular weight: 463.61.Its structural formula is:
In research process, repeat the method that existing document is recorded, the bilastine impurity number obtained is more, and total impurities is higher.The bilastine that the present invention obtains, containing a crystal water, the advantage had: purity is high, maximum contaminant is less than 1 ‰; Good stability, even if moisture absorption weightening finish is also not obvious under high humidity conditions.
Summary of the invention
One object of the present invention, discloses a kind of bilastine hydrate.
Another object of the present invention, discloses the preparation method of bilastine hydrate.
Another object of the present invention, discloses the pharmaceutical composition comprising bilastine hydrate.
The invention also discloses bilastine hydrate and manufacture the application in treatment allergic rhinoconjunctivitis and urticaria medicine.
Now in conjunction with object of the present invention, content of the present invention is specifically described.
The invention provides a kind of bilastine hydrate (shown in formula I),
（Ⅰ）
Karl_Fischer method (Karl Fischer method) a kind ofly measures in all kinds of chemical processes of moisture in material, and, method the most accurately the most single-minded to water, has been listed in the standard method of moisture determination in many materials, especially organic compound, reliable results.
After sample constant weight, through 6 batches of mensuration, the moisture that described invention compound contains is between 3.62%-3.84% (weight percent).In bilastine monohydrate, the theoretical content of water is 3.73%, can assert that invention compound contains a crystal water.
This bilastine monohydrate crystal, adopts D/Max-2500.9161 type x-ray diffractometer to measure, condition determination: Cu Ka target, tube voltage 40KV, tube current 100mA.X-ray powder diffraction charateristic avsorption band (2 θ), d value and relative intensity as follows.
| Spectral line number | 2 θ (degree) | Spacing (d) | I/I 0 |
| 1 | 8.040 | 6.8471 | 3 |
| 2 | 9.060 | 6.1014 | 3 |
| 3 | 10.340 | 5.2352 | 100 |
| 4 | 12.280 | 5.0073 | 8 |
| 5 | 14.160 | 4.9095 | 7 |
| 6 | 15.020 | 4.6536 | 2 |
| 7 | 17.390 | 3.5162 | 8 |
| 8 | 19.020 | 3.3113 | 90 |
| 9 | 20.000 | 3.1552 | 50 |
| 10 | 22.560 | 3.0102 | 11 |
| 11 | 24.250 | 2.9417 | 3 |
| 12 | 26.850 | 2.8901 | 2 |
| 13 | 30.740 | 2.7359 | 2 |
| 14 | 31.430 | 2.6712 | 5 |
| 15 | 32.960 | 2.5946 | 4 |
| 16 | 35.380 | 2.5349 | 2 |
| 17 | 37.420 | 2.4013 | 10 |
| 18 | 39.180 | 2.2574 | 2 |
| 19 | 39.920 | 2.1505 | 3 |
In the present invention, the mensuration of 2 θ values uses light source, and precision is ± 0.2 °, and therefore represent above-mentioned got value and allowed certain reasonably limit of error, its limit of error is ± 0.2 °.
Another object of the present invention, the preparation method of bilastine hydrate crystal.
The present inventor is by a large amount of experiments, explore refining solvent and the relation of bilastine crystal obtained, by bilastine is dissolved in ethanol-acetic acid-heated in water solution, then lower the temperature stage by stage, obtain the preparation method of bilastine hydrate crystal of the present invention.
Specifically comprise the following steps:: bilastine adds in the mixed solution of 3-4 times of (weight or measurement (WM) ratio) ethanol-acetic acid-water=7-4:1.5-2:4-8, be heated to 50 DEG C-60 DEG C, filtered while hot, be cooled to 30-35 DEG C, insulation 2-3 hour, and then be cooled to 20 DEG C-25 DEG C, insulation 2-3 hour, crystallization, filter, drying obtains the above-mentioned bilastine hydrate crystal of high purity.
The method is reproducible, is amplified to pilot scale, and optical purity and crystal formation all can reappear very well.
Another object of the present invention, provides the composition comprising the bilastine hydrate that bilastine hydrate crystal and one or more pharmaceutically acceptable carriers form.
Pharmaceutical composition of the present invention is prepared as follows: use standard and conventional technology; the compounds of this invention acceptable solid or liquid vehicle on technology of pharmaceutics are combined, and make it at random on technology of pharmaceutics acceptable auxiliary and vehicle be combined and be prepared into particulate or microballoon.Said composition is for the preparation of oral preparations.
The amount of the active ingredient (the compounds of this invention) contained in pharmaceutical composition and unit dosage form specifically can be applied according to the situation of the state of an illness of patient, diagnosis, the amount of compound used or concentration regulate in a wider scope, and the weight range of active compound is 0.5% ~ 20%(weight of composition).
Present invention also offers bilastine hydrate and manufacture the application in treatment allergic rhinoconjunctivitis and urticaria medicine.
stability test
The chemical stability of contriver to crystal formation of the present invention is studied, and investigation condition is high temperature (60 DEG C ± 2 DEG C), strong illumination (4500Lx ± 500lx), and high humidity (92.5%, RH) inspection target is outward appearance, content and related substance.
Result: from 0-10 days under high light, high temperature, super-humid conditions, outward appearance, related substance, content do not change, and illustrate that chemical stability is good, are applicable to manufacture and the standing storage of pharmaceutical preparation.
At 40 DEG C, under different relative humidity (RH) condition (75%, 92.5%), the mensuration of moisture in hydrate crystal of the present invention:
Result: at 40 DEG C, under different relative humidity (RH) condition (75%, 92.5%), water tariff collection is constant, and explanation has good stability, and is applicable to manufacture and the standing storage of pharmaceutical preparation.
embodiment:
Below in conjunction with embodiment, the present invention is described further, makes professional and technical personnel in the field better understand the present invention.Embodiment is only indicative, never means that it limits the scope of the invention by any way.
In the present invention, bilastine used can obtain according to by commercial sources, through proton nmr spectra, ultimate analysis, high resolution mass spectrometry confirmation, its chemical structure proves that chemical structure is correct.
The moisture recorded with Karl_Fischer method is 0.19%.
embodiment 1
In the 3000ml reaction flask that stirring, thermometer, condenser are housed, add ethanol-acetic acid-water (6:2:5) mixed solution of 300 grams of bilastines and 1200ml, start stirring, be heated to 55 DEG C, treat whole clearly molten, filtered while hot.Be cooled to 30 DEG C, be incubated 2 hours; Then, be cooled to 20 DEG C, be incubated 2 hours, crystallization, filter, drying obtains the above-mentioned bilastine hydrate crystal of high purity 276.1 grams, optical purity 99.88%.Dissolvent residual detects and meets the requirements.
Measure through Karl_Fischer method, the moisture containing 3.80% (weight percent).
Use standard and conventional technology, make the compounds of this invention acceptable solid or liquid vehicle on technology of pharmaceutics be combined, and make it at random on technology of pharmaceutics acceptable auxiliary and vehicle be combined and be prepared into particulate or microballoon.Said composition is for the preparation of oral preparations.Only citing is illustrated, and never means that it limits the scope of the invention by any way.
embodiment 2
Tablet containing bilastine hydrate
Prescription: bilastine monohydrate 20 grams, polyvinylpyrrolidone 15 grams, Microcrystalline Cellulose 260 grams, 1B 10 grams, sodium starch glycolate 185 grams, Magnesium Stearate 5 grams, distilled water is appropriate, makes 10000.
Technique: bilastine monohydrate and vehicle are dissolved in 80 DEG C of distilled water containing 1B, one of percentage adding Microcrystalline Cellulose is measured, and mixing final vacuum dry, pulverize, and crosses 100 mesh sieves, compressing tablet after mixing with other material.
Claims (6)
1. the hydrate of bilastine shown in formula I,
（Ⅰ）
Measure with Karl_Fischer method, described hydrate contains the moisture of 3.62%-3.84%;
The crystal of described bilastine hydrate, in measuring as characteristic X-ray powder with CuKa ray, its collection of illustrative plates has following 2 θ diffraction angle and relative intensity I/I
0:
The error of 2 θ diffraction angle is ± 0.2.
2. the preparation method of bilastine hydrate crystal described in claim 1, by being dissolved in ethanol-acetic acid-heated in water solution by bilastine, then cooling obtains stage by stage.
3. according to the method for claim 2, it is characterized in that comprising the following steps: that bilastine adds in the mixed solution of 3-4 times of (weight or measurement (WM) ratio) ethanol-acetic acid-water=7-4:1.5-2:4-8, be heated to 50 DEG C-60 DEG C, filtered while hot, be cooled to 30-35 DEG C, insulation 2-3 hour, and then be cooled to 20 DEG C-25 DEG C, insulation 2-3 hour, crystallization, filter, drying obtains.
4. the composition of the bilastine hydrate formed containing bilastine hydrate crystal according to claim 1 and one or more pharmaceutically acceptable carriers.
5. the composition of bilastine hydrate according to claim 4, is characterized in that said composition is for the preparation of oral preparations.
6. bilastine hydrate described in claim 1 is manufacturing the application in treatment allergic rhinoconjunctivitis and urticaria medicine.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201310413289.5A CN104447683A (en) | 2013-09-12 | 2013-09-12 | Stable Bilastine compound |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201310413289.5A CN104447683A (en) | 2013-09-12 | 2013-09-12 | Stable Bilastine compound |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN104447683A true CN104447683A (en) | 2015-03-25 |
Family
ID=52894507
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201310413289.5A Pending CN104447683A (en) | 2013-09-12 | 2013-09-12 | Stable Bilastine compound |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN104447683A (en) |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2017017301A1 (en) * | 2015-07-24 | 2017-02-02 | Urquima, S.A | Crystalline forms of bilastine and preparation methods thereof |
| CN106692090A (en) * | 2017-02-14 | 2017-05-24 | 万全万特制药（厦门）有限公司 | Bilastine tablets and preparation method thereof |
| WO2017167949A1 (en) | 2016-04-01 | 2017-10-05 | Krka, D.D., Novo Mesto | Crystalline forms of bilastine |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1176964A (en) * | 1996-06-04 | 1998-03-25 | 西班牙化工品与医药产品生产股份公司 | New benzimidazole derivatives with antihistaminic activity |
| WO2007047253A2 (en) * | 2005-10-11 | 2007-04-26 | Eastman Chemical Company | Pharmaceutical formulations of cyclodextrins and antifungal azole compounds |
| CN103214454A (en) * | 2013-03-30 | 2013-07-24 | 北京万全德众医药生物技术有限公司 | Bilastine crystal and preparation method thereof |
| CN103214455A (en) * | 2013-03-30 | 2013-07-24 | 北京万全德众医药生物技术有限公司 | Method for preparing bilastine |
-
2013
- 2013-09-12 CN CN201310413289.5A patent/CN104447683A/en active Pending
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1176964A (en) * | 1996-06-04 | 1998-03-25 | 西班牙化工品与医药产品生产股份公司 | New benzimidazole derivatives with antihistaminic activity |
| WO2007047253A2 (en) * | 2005-10-11 | 2007-04-26 | Eastman Chemical Company | Pharmaceutical formulations of cyclodextrins and antifungal azole compounds |
| CN103214454A (en) * | 2013-03-30 | 2013-07-24 | 北京万全德众医药生物技术有限公司 | Bilastine crystal and preparation method thereof |
| CN103214455A (en) * | 2013-03-30 | 2013-07-24 | 北京万全德众医药生物技术有限公司 | Method for preparing bilastine |
Cited By (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2017017301A1 (en) * | 2015-07-24 | 2017-02-02 | Urquima, S.A | Crystalline forms of bilastine and preparation methods thereof |
| CN107849007A (en) * | 2015-07-24 | 2018-03-27 | 乌奎玛公司 | Crystal formation of bilastine and preparation method thereof |
| JP2018522945A (en) * | 2015-07-24 | 2018-08-16 | ウルキマ，ソシエダッド アノニマ | Crystalline forms of bilastin and methods for their preparation |
| EP3327012A4 (en) * | 2015-07-24 | 2018-12-19 | Disproquima, S.A. | Crystalline forms of bilastine and preparation methods thereof |
| JP7168447B2 (en) | 2015-07-24 | 2022-11-09 | ウルキマ，ソシエダッド アノニマ | Crystal forms of bilastine and methods for their preparation |
| CN107849007B (en) * | 2015-07-24 | 2024-08-09 | 乌奎玛公司 | Crystal form of bilastine and preparation method thereof |
| WO2017167949A1 (en) | 2016-04-01 | 2017-10-05 | Krka, D.D., Novo Mesto | Crystalline forms of bilastine |
| CN106692090A (en) * | 2017-02-14 | 2017-05-24 | 万全万特制药（厦门）有限公司 | Bilastine tablets and preparation method thereof |
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Application publication date: 20150325 |