MXPA96003110A - Biodisponible crystal shape of cefuroximaaxe - Google Patents
Biodisponible crystal shape of cefuroximaaxeInfo
- Publication number
- MXPA96003110A MXPA96003110A MXPA/A/1996/003110A MX9603110A MXPA96003110A MX PA96003110 A MXPA96003110 A MX PA96003110A MX 9603110 A MX9603110 A MX 9603110A MX PA96003110 A MXPA96003110 A MX PA96003110A
- Authority
- MX
- Mexico
- Prior art keywords
- cefuroxime axetil
- crystalline form
- water
- crystal
- bioavailable
- Prior art date
Links
- KEJCWVGMRLCZQQ-DJMWJSSGSA-N 1-acetyloxyethyl (6R,7R)-3-(carbamoyloxymethyl)-7-[[(2E)-2-(furan-2-yl)-2-methoxyiminoacetyl]amino]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate Chemical compound N([C@@H]1C(N2C(=C(COC(N)=O)CS[C@@H]21)C(=O)OC(C)OC(C)=O)=O)C(=O)/C(=N/OC)C1=CC=CO1 KEJCWVGMRLCZQQ-DJMWJSSGSA-N 0.000 claims abstract description 17
- 229960002620 cefuroxime axetil Drugs 0.000 claims abstract description 17
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 13
- 239000000203 mixture Substances 0.000 claims abstract description 7
- 238000001816 cooling Methods 0.000 claims abstract description 3
- 239000003960 organic solvent Substances 0.000 claims abstract description 3
- 238000000034 method Methods 0.000 claims description 3
- 238000002083 X-ray spectrum Methods 0.000 claims description 2
- 150000001875 compounds Chemical class 0.000 claims 1
- 238000002955 isolation Methods 0.000 claims 1
- 238000000926 separation method Methods 0.000 abstract 1
- 239000000047 product Substances 0.000 description 16
- 238000001228 spectrum Methods 0.000 description 8
- XEKOWRVHYACXOJ-UHFFFAOYSA-N acetic acid ethyl ester Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 6
- 238000002329 infrared spectrum Methods 0.000 description 6
- 238000002360 preparation method Methods 0.000 description 5
- JFPVXVDWJQMJEE-IZRZKJBUSA-N (6R,7R)-3-[(carbamoyloxy)methyl]-7-[(2Z)-2-(furan-2-yl)-2-(methoxyimino)acetamido]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid Chemical compound N([C@@H]1C(N2C(=C(COC(N)=O)CS[C@@H]21)C(O)=O)=O)C(=O)\C(=N/OC)C1=CC=CO1 JFPVXVDWJQMJEE-IZRZKJBUSA-N 0.000 description 4
- 238000003756 stirring Methods 0.000 description 4
- 229950003588 Axetil Drugs 0.000 description 3
- 230000036912 Bioavailability Effects 0.000 description 3
- 229960001668 Cefuroxime Drugs 0.000 description 3
- 238000002441 X-ray diffraction Methods 0.000 description 3
- 238000004458 analytical method Methods 0.000 description 3
- 230000035514 bioavailability Effects 0.000 description 3
- 239000007787 solid Substances 0.000 description 3
- 210000001124 Body Fluids Anatomy 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N HCl Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- UIIMBOGNXHQVGW-UHFFFAOYSA-M NaHCO3 Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
- IKHGUXGNUITLKF-UHFFFAOYSA-N acetaldehyde Chemical compound CC=O IKHGUXGNUITLKF-UHFFFAOYSA-N 0.000 description 2
- WEVYAHXRMPXWCK-UHFFFAOYSA-N acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 2
- 238000007792 addition Methods 0.000 description 2
- 230000000844 anti-bacterial Effects 0.000 description 2
- 239000010839 body fluid Substances 0.000 description 2
- 238000006243 chemical reaction Methods 0.000 description 2
- RTZKZFJDLAIYFH-UHFFFAOYSA-N diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
- OKKJLVBELUTLKV-UHFFFAOYSA-N methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 2
- 239000012074 organic phase Substances 0.000 description 2
- IOLCXVTUBQKXJR-UHFFFAOYSA-M potassium bromide Inorganic materials [K+].[Br-] IOLCXVTUBQKXJR-UHFFFAOYSA-M 0.000 description 2
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
- CDBYLPFSWZWCQE-UHFFFAOYSA-L sodium carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- XTWYTFMLZFPYCI-KQYNXXCUSA-N 5'-adenylphosphoric acid Chemical compound C1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](COP(O)(=O)OP(O)(O)=O)[C@@H](O)[C@H]1O XTWYTFMLZFPYCI-KQYNXXCUSA-N 0.000 description 1
- FXXACINHVKSMDR-UHFFFAOYSA-N Acetyl bromide Chemical compound CC(Br)=O FXXACINHVKSMDR-UHFFFAOYSA-N 0.000 description 1
- 229960000534 Cefuroxime sodium Drugs 0.000 description 1
- 238000005033 Fourier transform infrared spectroscopy Methods 0.000 description 1
- 102100010926 PRPF6 Human genes 0.000 description 1
- 101710018068 PRPF6 Proteins 0.000 description 1
- JIAARYAFYJHUJI-UHFFFAOYSA-L Zinc chloride Chemical compound [Cl-].[Cl-].[Zn+2] JIAARYAFYJHUJI-UHFFFAOYSA-L 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 239000008346 aqueous phase Substances 0.000 description 1
- 102000006635 beta-Lactamases Human genes 0.000 description 1
- 108020004256 beta-Lactamases Proteins 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 150000001780 cephalosporins Chemical class 0.000 description 1
- 238000010276 construction Methods 0.000 description 1
- RYGMFSIKBFXOCR-UHFFFAOYSA-N copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 1
- 229910052802 copper Inorganic materials 0.000 description 1
- 239000010949 copper Substances 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000005712 crystallization Effects 0.000 description 1
- 238000010192 crystallographic characterization Methods 0.000 description 1
- ZAFNJMIOTHYJRJ-UHFFFAOYSA-N diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 244000005700 microbiome Species 0.000 description 1
- 239000012071 phase Substances 0.000 description 1
- 239000008363 phosphate buffer Substances 0.000 description 1
- 239000001184 potassium carbonate Substances 0.000 description 1
- 229910000027 potassium carbonate Inorganic materials 0.000 description 1
- 239000000651 prodrug Substances 0.000 description 1
- 229940002612 prodrugs Drugs 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 239000001187 sodium carbonate Substances 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 239000012265 solid product Substances 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 230000001131 transforming Effects 0.000 description 1
- 238000002834 transmittance Methods 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 239000011592 zinc chloride Substances 0.000 description 1
- 235000005074 zinc chloride Nutrition 0.000 description 1
Abstract
The present invention relates to a bioavailable crystalline form of cefuroxime axetil, obtained by the treatment of known cefuroxime axetil crystalline or amorphous, with water or with an organic solvent miscible with water, or with a mixture thereof, at a temperature between + 20 and + 100 ° C, followed by cooling and separation of the crystalline product by known methods
Description
BIODISPONIBLE CRYSTALLINE SHAPE OF CEFUROXIMA AXETIL
DESCRIPTION OF THE INVENTION The present invention relates to a bioavailable crystalline form of cefuroxi to axetil, that is to say, of 1-acetoxietiéster of the acid (6R, 7R) -3-carbamoi 1-oxymethi l-7- [(Z) - 2- (fur-2-i 1) -2-methoxy iminoacetamido] -3-cephem-4-carboxylic acid. Cefuroxime is a known product, its preparation being described in US Patent No. US-A-3, 74, 153. This has a good spectrum of antibacterial activity, extending both to gram-positive and gram-negative microorganisms. Cefuroxime can not be used as such for oral administration, because it is not absorbed and does not enter the circulation of body fluids. Cefuroxime axetil is a prodrug for oral administration, which has a high stability against ß-lactamase-producing strains. In this regard, once the ester has been absorbed and has entered the circulation of body fluids, it is hydrolyzed to release cefuroxime, which is actually responsible for the antibacterial activity. Example 1 of the British Patent GB-A-1,571,683 describes for the first time the preparation of cefuroxime axetil in a crystalline form, referred to in REF: 22809 hereinafter as the "a-crystal" form: the characterization of the Infrared (IR) a-crystal form, with reference to Example 1 of British Patent GB-A-2, 145, 409 of Glaxo Group, Ltd. However, the α-crystalline form of cefuroxime axetil does not possess the necessary bioavailability characteristics, while it is known that orally administered cephalosporins (and medications in general) must be in a highly bioavailable form. In this regard, the commercially available cefuroxime axetil registered worldwide is in substantially amorphous form, as described and claimed in US Patent No. US-A-4,562,181 in the name of Glaxo Group, Ltd., which establishes that "the crystalline product" (a-crystal) "does not possess the best balance of properties for commercial use" (page 2, lines 3-6), while "the substantially amorphous form has a higher bioavailability after the oral administration, than the crystalline form "(page 2, lines 10 to 15). In this regard, it should be noted that, as recognized by Glaxo in US Patent No. US-A-4, 562-181, in general, crystalline forms have the best balance between physicochemical and biological properties and good stability, both during storage as during the commercialization (page 1, lines 57-61). It is evident, from Example 1 which is presented below, which forms part of the present disclosure, that the methods described in Example 1 of British Patent GB-A-2, 145,409 and in Preparation 2"of the U.S. Patent No. US-A-4,562,181, have been faithfully followed to obtain cefuroxime axetil in a-crystal-ina form, for which an infrared (IR) analysis was performed in KBr.This analysis of IR is confirmed, particularly within the -1 region between 1000 and 500 cm by the spectrum published in the cited patent, showing a substantial identity between the two IR spectra.Thus, even to date, regardless of the studies carried out in the world in this field, only the α-crystalline form of cefuroxime axetil (which is not bioavailable) and the substantially amorphous form (which is bioavailable) are known In accordance with the present invention, it has surprisingly been found that if the cefurox An axetil in a-crystalline form or in a substantially amorphous form is treated with a mixture of water and an organic solvent miscible with water, in a weight ratio between 100: 0 and 0: 100 at a temperature between +20 and +100. "C, followed by cooling, yields a cefuroxime axetil in crystalline form which is different from the α-crystalline form and which will be referred to hereinafter as the 0-crystalline or β-crystal form. AgainSurprisingly, it has been found that the ß-crystal form has good bioavailability characteristics, which make it suitable for use in therapy, with an excellent balance between physicochemical and biological properties and good stability during storage and commercialization. , as stated by Glaxo in his US Patent No. US-A-4, 562, 181. As will be seen in the experimental part, the IR spectrum of the 0-crystal was obtained by the same method as for the -crystal. In this way, it was found that the two IR spectra are substantially different from one another, particularly within the region between 1000 and 5000 cm "1. For greater certainty, the X-ray spectrum (XR spectrum) was also obtained for the a-crystals and β-crystals, decisively demonstrating, in this way, their different structure The reactions illustrated in the Examples were followed by CLAP (mobile phase: 30 * of acetonitrile, 70% of phosphate buffer 0.03; Lichrospher RP60 Select B 5¿ column, temperature controlled at 45 ° C; 270 nm UV detector; elusion 1.7 l / min). The IR spectra were obtained in solid state (in KBr tablets) using an FT-IR 8101M SHIMADZU apparatus. The X-ray diffraction spectra were determined in the powdered crystals, using a diffractometer PHILIPS P 1710, emitting radiation at wavelengths of 1.54051 A and 1.54433 A, produced by an X-ray tube with copper anode, to a generator voltage of 40 KV and one. Current strength of 40 mA in the generator. The samples submitted to the test were mounted on a NISKAMEN sample carrier to avoid preferential orientation. The data obtained were collected after calibrating the device with an external standard, the reading and graphical construction of the spectrum being executed, with an ADP 3.6 PC program. EXAMPLE 1 The a-crystalline form was synthesized following as faithfully as possible the preparation described in Example 1 of British Patent No. GB-A-2, 145,409 and in Preparation 2 of US Patent No. US-A- 4,562,181. In this way, 12.5 g of (RS) -l-acetoxiethiumbromide were prepared by reacting 3.30 g of acetaldehyde with 9.20 g of acetyl bromide in 30 ml of DMAC and 12 mg of anhydrous zinc chloride for 4 h at -10 ° C. . The solution prepared in this way was added to a suspension, under stirring, of 20 g of cefuroxime sodium in 80 ml of DMAC. The reaction was carried out for 90 min at -1 ° C with the addition of 0.5 g of potassium carbonate, and was left to last for an additional two hours at a temperature between +1 and + 3'C. Subsequently, the reaction mixture was added rapidly to a mixture of 200 ml of ethyl acetate and 200 ml of a 3% solution of sodium carbonate. After stirring for 1 h, the organic phase was separated, washed again with 100 ml of a normal solution of hydrochloric acid and then with 30 ml of a 20 * NaCl solution containing 2% sodium bicarbonate. All these aqueous phases were mixed and reextracted with 100 ml of ethyl acetate, the organic phase being blended and decolorized with carbon (2 g) at room temperature for 30 min. After filtration, the solvent was removed under vacuum at 20 ° C, the system was concentrated to 150 g and stirred for 1 h at room temperature until substantial crystallization was obtained. 250 ml of diisopropyl ether was added slowly (over a period of 45 min) and stirring continued for an additional hour. The product was vacuum filtered and washed with a 1: 2 acetate / ether mixture. The product, when vacuum dried at 50 ° C, provided a product, from which a sample (identified as 115/5 FP) was taken which proved to have the IR and XR spectra shown in Figures 1 and 2, respectively, characteristic of the a-crystal. -1 In Figure 1, the horizontal axis indicates cm and the vertical axis indicates percentage of transmittance (% T). In Figure 2, the horizontal axis indicates the angle, while the vertical axis indicates the intensity of the peaks. In Figure 2 it can be seen that the X-ray diffraction spectrum of the a-crystal has the following characteristics.
Angle (* 20) Relative Intensity. { %)
. 555 18.1 5.850 7.7 7.770 100.0 8.765 39.6 9.055 42.0 11.120 23.2 11.855 34.4 12.525 26.2 14.160 13.3 Angle ("20) Relative Intensity (*)
. 695 23.2 17.950 38.4 19.590 37.3 20.025 49.5 20,600 36.6 20.860 38.1 21.485 27.5 22.565 67.4 23.815 47.8 24.900 50.4 26.075 23.8 26.700 35.1 28.015 13.3 29.170 11.5 30.235 10.3 30.830 6.7 31.780 15.1 33.120 9.9 33.735 6.7 Angle (° 20) Intensity Relative (%)
36. 695 6.7 40.850 8.1 43.870 4.7 46.505 3.2 54.590 0.0 55.640 1.4 57.215 3.2 58.135 4.4
EXAMPLE 2 The a-crystal obtained in Example 1 is transformed to the 0-crystal form by the following method: 15 g of a-cefuroxime axetil are suspended in 150 ml of water, the system is heated at 40 * C for 3 h , the product is filtered under vacuum and washed with water. The obtained product is dried under vacuum at 40 ° C, to obtain 14 g of a solid product (β-crystal) which shows the same R / S as the starting product. A sample of the crystalline product of the form 0 obtained in this way (identified as 104/5 FP), was analyzed to obtain the IR spectrum shown in Figure 3, and the XR spectrum shown in Figure 4. The horizontal axes and vertical indicate the same amounts as in Figures 1 and 2. It can be seen that the X-ray diffraction spectrum of the 0-crystal has the following characteristics.
Angle (° 20) Relative Intensity (%)
7. 585 35.7 8.200 15.3 9.195 62.9 9.405 6.3 10.385 21.5 11.875 23.6 12.530 62.0 12.605 53.6 12.840 19.5 13.960 19.0 14.460 7.2 14.870 2.8 15.535 10.1 15.895 29.4 16.270 17.1 16.545 12.8 16.910 68.4 Angle ("20) Relative Intensity (%)
18. 270 71.2 18.830 21.5 19.035 19.0 23.565 14.4 24.665 14.0 20.500 28.8 21.260 100.0 21.930 28.8 22.495 31.8 22.785 36.4 23.080 19.0 23.565 14.4 24.865 46.5 25.425 42.7 26.225 15.7 26.880 14.4 27.950 10.1 28.910 11.2 30.270 8.8 30.965 10.5 31.990 8.4 32.405 5.0 33.340 3.6 Angle ("20) Intensity Relative (%)
34. 820 17.6 36.355 5.5 37.500 4.3 38.560 5.0 39.320 6.6 40.590 3.4 41.300 3.0 42.360 4.3 43.410 5.0 44.840 2.3 46.605 2.6 49.615 1.1 51.045 1.2 52.620 2.3
EXAMPLE 3 20 g of cefuroxime axetil (prepared by the method reported in British Patent GB-A-1, 571,683) was dissolved in 500 ml of methanol at 40 * C; while this hot solution was maintained, 1000 ml of water kept at 40 * C were added slowly. When the addition was complete, the system was cooled to room temperature and vacuum filtered, washing the product with water. The dry product (13.5 g) has an R / S ratio of 0.85: 1, while the starting product had an R / S ratio of 0.94: 1. The solid (ß-crystal) shows a different IR and XR profile than the starting product, as indicated in Figures 3 and 4. EXAMPLE 4 50 g of cefuroxime axetil are spray-dried in substantially amorphous form , in 500 ml of water and heated to 40 ° C, maintaining stirring for 3 hours.The system is cooled to room temperature and filtered, the product is washed with water.The dry solid provides 46 g of product, which in the Analysis of IR and XR shows its transformation to 0-crystal The ratio R / S is 1.2 / 1.0 EXAMPLE 5 5 g of amorphous cefuroxime axetil (obtained by the procedure described in Example 22 of the US Patent No. US-A-4, 562, 181) at 40 * C for 3 hours, with 50 ml of water The dry product (4.8 g) has an R / S ratio of 0.64 and an IR spectrum similar to that shown in the Figure 3 (0-crystal) It is noted that in relation to this date, the best method known by the applicant to bring the practice said invention is that which is clear from the present description of the invention.
Having described the invention as an antecedent, what is contained in the following is claimed as property.
Claims (4)
- CLAIMS 1. A bioavailable crystalline form of cefuroxime axetil, characterized by having the following X-ray spectrum; angle C20) Relative Intensity (%) 7. 585 35.7 8.200 15.3 9.195 62.9 9.405 6.3 10.385 21.5 11.875 23.6 12.530 62.0 12.605 53.6 12.840 19.5 13.960 19.0 14.460 7.2 14.870 2.8 15.535 10.1 15.895 29.4 16.270 17.1 16.545 12.8 16.910 68.4 Angle ("20) Relative Intensity (%) 18. 270 71.2 18.830 21.5 19.035 19.0 23.565 14.4 24.665 14.0 20.500 28.8 21.260 100.0 21.930 28.8 22.495 31.8 22.785 36.4 23.080 19.0 23.565 14.4 24.865 46.5 25.425 42.7 26.225 15.7 26.880 14.4 27.950 10.1 28.910 11.2 30.270 8.8 30.965 10.5 31.990 8.4 32.405 5.0 33.340 3.6 Angle ('20) Intensity Relative (%) 34. 820 17.6 36.355 5.5 37.500 4.3 38.560 5.0 39.320 6.6 40.590 3.4 41.300 3.0 42.360 4.3 43.410 5.0 44.840 2.3 46.605 2.6 49.615 1.1 51.045 1.2 52.620 2.3
- 2. A bioavailable crystalline form of cefuroxime axetil according to claim 1, characterized in that it consists of a mixture of diastereoisomers R / S, in a ratio between 0: 1.0 and 1.0: 0.
- 3. A bioavailable crystalline form of cefuroxime axetil according to claim 2, characterized in that the ratio of diastereomers in the mixture is between 0.9: 1.1 and 1.1: 0.9.
- 4. A process for producing a bioavailable crystalline form of cefuroxime axetil according to claim 1, characterized in that said cefuroxime axetil in crystalline form or in substantially amorphous form, is treated with a mixture of water and an organic solvent miscible with water . in a weight ratio between 100: 0 and 0: 100, at a temperature between +20 and +100 * C, for a time between a few minutes and several hours, followed by cooling and isolation of the crystalline compound by the normal methods of The technique.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| MIMI95A001716 | 1995-08-03 | ||
| IT95MI001716A IT1277426B1 (en) | 1995-08-03 | 1995-08-03 | BIOAVAILABLE CRYSTALLINE FORM OF CEFUROXIMA AXETIL |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| MXPA96003110A true MXPA96003110A (en) | 1997-06-01 |
| MX9603110A MX9603110A (en) | 1997-06-28 |
Family
ID=11372130
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| MX9603110A MX9603110A (en) | 1995-08-03 | 1996-07-31 | Crystalline-bioavailable axetyl cephuroxime. |
Country Status (24)
| Country | Link |
|---|---|
| US (1) | US5677443A (en) |
| EP (1) | EP0757991B1 (en) |
| JP (1) | JPH09104685A (en) |
| KR (1) | KR970010776A (en) |
| CN (1) | CN1055693C (en) |
| AR (1) | AR003973A1 (en) |
| AT (1) | ATE195126T1 (en) |
| BR (1) | BR9603270A (en) |
| CA (1) | CA2179359A1 (en) |
| DE (1) | DE69609576T2 (en) |
| DK (1) | DK0757991T3 (en) |
| ES (1) | ES2150052T3 (en) |
| FI (1) | FI962937A (en) |
| GR (1) | GR3034663T3 (en) |
| IL (1) | IL118822A (en) |
| IT (1) | IT1277426B1 (en) |
| MX (1) | MX9603110A (en) |
| PT (1) | PT757991E (en) |
| RU (1) | RU2155767C2 (en) |
| SI (1) | SI0757991T1 (en) |
| TR (1) | TR199600691A2 (en) |
| TW (1) | TW413635B (en) |
| UA (1) | UA46727C2 (en) |
| ZA (1) | ZA965234B (en) |
Families Citing this family (19)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FR2725382B1 (en) * | 1994-10-05 | 1997-01-03 | Commissariat Energie Atomique | POLYAZACYCLOALCANES, TRI-, TETRA- OR PENTAAZAMACROCYCLIC COMPLEXES, PROCESS FOR MANUFACTURING SUCH SUBSTITUTED OR NON-SUBSTITUTED POLYAZACYCLOALCANES AND GRAFTS ON A SUPPORT AND USES OF POLYAZACYCLOALCANES |
| NZ299077A (en) * | 1996-07-26 | 1998-06-26 | Apotex Inc | Preparation of amorphous cefuroxime axetil (a cephalosporin derivative) by dissolving crystalline cefuroxim axetil in a highly polar solvent, typically dmso and/or dmf |
| KR100401284B1 (en) * | 1997-06-03 | 2004-01-31 | 주식회사유한양행 | Method for preparing 1-bromoethyl acetate |
| CA2209868C (en) * | 1997-08-15 | 2001-08-14 | Bernard Charles Sherman | Pharmaceutical compositions comprising cefuroxime axetil |
| IN186539B (en) * | 1997-09-29 | 2001-09-29 | Ranbaxy Lab Ltd | |
| ATE212638T1 (en) * | 1998-02-20 | 2002-02-15 | Fako Ilaclari A S | METHOD FOR PRODUCING SOLUBLE CRYSTALLINE CEFUROXIM AXETIL |
| US6384213B1 (en) | 1998-10-23 | 2002-05-07 | Ranbaxy Laboratories Limited | Process for preparing a pure, pharmacopoeial grade amorphous form of cefuroxime axetil |
| IN190849B (en) * | 2000-07-17 | 2003-08-23 | Ranbaxy Lab Ltd | |
| ITMI20011763A1 (en) * | 2001-08-10 | 2003-02-10 | Antibioticos Spa | HIGH-PURITY CEFUROXIME AXELITE PREPARATION PROCESS |
| ITMI20011925A1 (en) * | 2001-09-14 | 2003-03-14 | Antibioticos Spa | METHOD APPLICABLE ON INDUSTRIAL SCALE FOR THE PREPARATION OF CEFUROXIME AXETILE CRISTALLINO |
| HRP20020923A2 (en) * | 2001-11-23 | 2003-10-31 | Glaxo Group Ltd | Pharmaceutical composition |
| JP2007517864A (en) * | 2004-01-09 | 2007-07-05 | ハンミ ファーム． シーオー．， エルティーディー． | Cefuroxime axetil granules and method for producing the same |
| CN100448879C (en) * | 2004-07-22 | 2009-01-07 | 北京化工大学 | Method for preparing unformed cefuroxime axetil |
| DE102005019458A1 (en) * | 2005-04-25 | 2006-10-26 | Grünenthal GmbH | Composition, useful in the preparation of pellets and the multi-particular-presentation form, comprises cefuroximaxetil and carrageenan of the group of lambda carrageenan, tau carrageenan and kappa carrageenan |
| US8900637B2 (en) * | 2005-12-02 | 2014-12-02 | Lupin Limited | Stable taste masked formulations of cephalosporins |
| DE102006019619A1 (en) * | 2006-04-25 | 2007-10-31 | Grünenthal GmbH | Crystalline modification of cefuroxime axetil |
| CN102417451B (en) * | 2011-12-20 | 2013-12-04 | 浙江国邦药业有限公司 | Method for synthesizing (R,S)1-bromoethyl acetate |
| WO2014040239A1 (en) * | 2012-09-12 | 2014-03-20 | 海南卫康制药(潜山)有限公司 | Cefuroxime sodium crystal compound and composition powder injection thereof |
| CN106554361B (en) * | 2016-09-30 | 2018-10-09 | 华北制药河北华民药业有限责任公司 | A kind of preparation method of CEFUROXIME AXETIL oral preparation |
Family Cites Families (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CA1094545A (en) * | 1976-02-16 | 1981-01-27 | Michael Gregson | Cephalosporin antibiotics |
| GB1571683A (en) * | 1976-02-16 | 1980-07-16 | Glaxo Operations Ltd | Ester derivatives of cefuroxime |
| YU44680B (en) * | 1982-07-30 | 1990-12-31 | Glaxo Lab Ltd | Process for obtaining very pure amorphous form of cephuroxim axetile |
| GB8320521D0 (en) * | 1983-07-29 | 1983-09-01 | Glaxo Group Ltd | Chemical process |
| US5063224A (en) * | 1990-07-09 | 1991-11-05 | Eli Lilly And Company | R-cefuroxime axetil |
-
1995
- 1995-08-03 IT IT95MI001716A patent/IT1277426B1/en active IP Right Grant
-
1996
- 1996-06-17 PT PT96109665T patent/PT757991E/en unknown
- 1996-06-17 EP EP96109665A patent/EP0757991B1/en not_active Expired - Lifetime
- 1996-06-17 ES ES96109665T patent/ES2150052T3/en not_active Expired - Lifetime
- 1996-06-17 DK DK96109665T patent/DK0757991T3/en active
- 1996-06-17 AT AT96109665T patent/ATE195126T1/en not_active IP Right Cessation
- 1996-06-17 US US08/664,552 patent/US5677443A/en not_active Expired - Fee Related
- 1996-06-17 DE DE69609576T patent/DE69609576T2/en not_active Expired - Fee Related
- 1996-06-17 SI SI9630229T patent/SI0757991T1/en unknown
- 1996-06-18 CA CA002179359A patent/CA2179359A1/en not_active Abandoned
- 1996-06-20 ZA ZA965234A patent/ZA965234B/en unknown
- 1996-06-25 TW TW085107604A patent/TW413635B/en not_active IP Right Cessation
- 1996-07-09 IL IL11882296A patent/IL118822A/en not_active IP Right Cessation
- 1996-07-23 FI FI962937A patent/FI962937A/en unknown
- 1996-07-30 KR KR1019960031374A patent/KR970010776A/en not_active Application Discontinuation
- 1996-07-31 MX MX9603110A patent/MX9603110A/en unknown
- 1996-08-01 CN CN96109271A patent/CN1055693C/en not_active Expired - Fee Related
- 1996-08-01 AR ARP960103834A patent/AR003973A1/en unknown
- 1996-08-02 RU RU96115329/04A patent/RU2155767C2/en active
- 1996-08-02 JP JP8205098A patent/JPH09104685A/en active Pending
- 1996-08-02 BR BR9603270A patent/BR9603270A/en not_active Application Discontinuation
- 1996-08-02 UA UA96083116A patent/UA46727C2/en unknown
- 1996-08-28 TR TR96/00691A patent/TR199600691A2/en unknown
-
2000
- 2000-10-23 GR GR20000402353T patent/GR3034663T3/en not_active IP Right Cessation
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