CN104262360A - Monocrystal form of faropenem sodium hydrate and preparation method thereof - Google Patents
Monocrystal form of faropenem sodium hydrate and preparation method thereof Download PDFInfo
- Publication number
- CN104262360A CN104262360A CN201410531418.5A CN201410531418A CN104262360A CN 104262360 A CN104262360 A CN 104262360A CN 201410531418 A CN201410531418 A CN 201410531418A CN 104262360 A CN104262360 A CN 104262360A
- Authority
- CN
- China
- Prior art keywords
- faropenem sodium
- equal
- sodium hydrate
- monocrystal
- preparation
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D499/00—Heterocyclic compounds containing 4-thia-1-azabicyclo [3.2.0] heptane ring systems, i.e. compounds containing a ring system of the formula:, e.g. penicillins, penems; Such ring systems being further condensed, e.g. 2,3-condensed with an oxygen-, nitrogen- or sulfur-containing hetero ring
- C07D499/88—Compounds with a double bond between positions 2 and 3 and a carbon atom having three bonds to hetero atoms with at the most one bond to halogen, e.g. an ester or nitrile radical, directly attached in position 2
- C07D499/893—Compounds with a double bond between positions 2 and 3 and a carbon atom having three bonds to hetero atoms with at the most one bond to halogen, e.g. an ester or nitrile radical, directly attached in position 2 with a hetero ring or a condensed hetero ring system, directly attached in position 3
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D499/00—Heterocyclic compounds containing 4-thia-1-azabicyclo [3.2.0] heptane ring systems, i.e. compounds containing a ring system of the formula:, e.g. penicillins, penems; Such ring systems being further condensed, e.g. 2,3-condensed with an oxygen-, nitrogen- or sulfur-containing hetero ring
- C07D499/04—Preparation
- C07D499/18—Separation; Purification
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B2200/00—Indexing scheme relating to specific properties of organic compounds
- C07B2200/13—Crystalline forms, e.g. polymorphs
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention provides a monocrystal form of faropenem sodium hydrate. The monocrystal form serves as an orthorhombic system, wherein the crystal axes of the monocrystal are as follows: a is equal to 5.4998(3) angstroms, b is equal to 9.2057(4) angstroms, and c is equal to 32.4371(12) angstroms; the crystal face included angles are as follows: alpha is equal to 90 degrees, beta is equal to 90 degrees, and lambda is equal to 90 degrees. The invention further provides a preparation method of the monocrystal form, which comprises the following steps: adding faropenem sodium to purified water, heating the mixture to 50 DEG C above until the solid is completely dissolved, stopping heating, slowly cooling the solution, and leaving the solution to stand for 48 hours above, separating out solids, and filtering and drying to obtain the product. The faropenem sodium hydrate with the monocrystal form, disclosed by the invention, has a more stable chemical property.
Description
Technical field
The present invention relates to faropenem sodium hydrate monocrystalline crystal formation and preparation method thereof, belong to chemical pharmacy field.
Background technology
The penems antibiotics that faropenem sodium hydrate (Faropenem sodium hydrate) is developed for Japanese Suntory company, goes on the market on September 15th, 1997 in Japan.Its structural formula is:
Chemistry full name is (5R, 6S)-6-[(1R)-1-hydroxyethyl]-7-oxo-3-[(2R)-tetrahydrofuran (THF)-2-base]-4-thia-1-azabicyclo [3.2.0] hept-2-ene"-2-sodium formiate two times of semihydrates, Faropenem sodium has broad spectrum antibiotic activity, not second to the tight amine of injection trains southern cilastatin sodium, to aerobism gram-positive microorganism, aerobism Gram-negative bacteria and anerobe have extensive anti-microbial effect, especially to the staphylococcus in aerobism gram-positive microorganism, not pull bar bacterium, suis, streptococcus pneumoniae, faecalis, citric acid bacillus in aerobism Gram-negative bacteria, enterobacteria, the white bacterium of Cray, Bacillus proteus, influenza bacterium, peptostreptococcus, propionibacterium, Whooping cough bites the peptostreptococcus in blood bacillus and anerobe, the stronger fungicidal effectiveness of the display such as bacterioide, anti-microbial activity is better than existing cephalosporin oral antibiotic, it is hospital severe infection patient optimal selection medication.
Faropenem sodium preparation method can see US4997829, EP410727, JP 92041489, J.Med.Chem, 1997,40:2126-2132.Due to β-lactam antibitics less stable, to thermally labile, therefore, stability of crystal form is very important.Patent CN100484942 discloses a kind of crystal formation of Faropenem sodium, but the crystal formation preparation method reported up to now can not ensure crystal form purity and stability of crystal form.The crystal form purity of monocrystalline crystal formation is general higher and stable, therefore, inventor developed a kind of faropenem sodium hydrate monocrystalline crystal formation.
Summary of the invention
The object of the invention is to overcome the deficiencies in the prior art part, a kind of faropenem sodium hydrate monocrystalline crystal formation and preparation method thereof is provided.
Faropenem sodium hydrate monocrystalline crystal formation of the present invention, be rhombic system, its crystallographic axis is
crystal face angle is α=90 °, β=90 °, λ=90 °.
The preparation method of monocrystalline crystal formation of the present invention, comprises the steps: addition method faropenem in purified water, is heated to more than 50 DEG C, dissolves completely to solid, stops heating, slow cooling static more than placement 48h, after separating out solid, filters, dry.
In the preparation process in accordance with the present invention, the Faropenem sodium obtained by any method can be used, the Faropenem sodium such as obtained by the preparation method described in document (J.Med.Chem, 1997,40:2126-2132).
Prove that the faropenem sodium hydrate of this monocrystalline crystal formation has more stable chemical property by stability test.
Accompanying drawing explanation
Fig. 1 is the molecular structure of the monocrystalline crystal formation of the faropenem sodium hydrate that embodiment 1 obtains.
Fig. 2 is the structure cell accumulation graph of the monocrystalline crystal formation of the faropenem sodium hydrate that embodiment 1 obtains.
Embodiment
With specific embodiment, technical scheme of the present invention is described below, but protection scope of the present invention is not limited thereto:
The preparation of embodiment 1 faropenem sodium hydrate monocrystalline crystal formation
5g Faropenem sodium is joined in 10mL purified water.At 50 DEG C, stir 10min all dissolve to solid and clarify, stop heating and non-shock chilling to room temperature, static placement 48h (prevent in single crystal growth process vibrations).Crystallization, filters, and washing, and 30 DEG C of vacuum-drying 10h, obtain faropenem sodium hydrate monocrystalline 4.6g, yield 92%.
The preparation of embodiment 2 faropenem sodium hydrate monocrystalline crystal formation
5g Faropenem sodium is joined in 20mL purified water.At 50 DEG C, stir 10min all dissolve to solid and clarify, stop heating and non-shock chilling to room temperature, static placement 48h (prevent in single crystal growth process vibrations).Crystallization, filters, and washing, and 30 DEG C of vacuum-drying 10h, obtain faropenem sodium hydrate monocrystalline 3.6g, yield 72%.
The mensuration of embodiment 3 crystalline structure
In basis for selecting embodiment 1, the obtained 0.20mm × 0.28mm × 0.21mm white prism-shaped crystal that is of a size of of method is settled on the glass fibers, at 121.16 (10) K temperature, carry out X-ray diffraction analysis.With graphite monochromatised MoKa ray on Rigaku SCXmini diffractometer Advances in crystal X-ray diffraction instrument
with
mode scans, and collects crystalline diffraction data, collect point diffraction 3473 altogether, wherein observable diffraction (I>2signm (I)) 3117 within the scope of °-28.60 °, θ=3.35, and for structural modifications.Diffraction data corrects through LP Summing Factor empirical absorption.Adopt direct method, and through the synthesis of number wheel difference Fourier, find whole non-hydrogen atom, hydrogen atom coordinate adopts geometry hydrogenation method to obtain.In structure, whole non-hydrogen atom adopts complete matrix least-squares refinement, and adopts anisotropy thermal parameter.All evaluation works all adopt SHELXL97 program to complete.
Table 1: the crystal data of Faropenem sodium
Table 2 part bond distance
Table 3 part bond angle (°)
Embodiment 4 prepares the pharmaceutical composition containing faropenem sodium hydrate monocrystalline
Prepare 1000 tablets of tablets containing faropenem sodium hydrate monocrystalline, wherein every sheet contains
The formula of 150mg activeconstituents is as follows:
The compound of embodiment 1 ... ... ... ... ... ... ... 150g
Microcrystalline Cellulose ... ... ... ... ... ... ... ... 60g
Micropowder silica gel ... ... ... ... ... ... ... ... ..10g
Cross-linked polyvinylpyrrolidone ... ... ... ... ... ... .36g
Low-substituted hydroxypropyl cellulose ... ... ... ... ... ... .20g
Aspartame ... ... ... ... ... ... ... ... .4g
PVP?K30.................................................4g
Magnesium Stearate (lubricant) ... ... ... ... ... ... ..0.8%
Method of pharmacy is granulated routinely, and compressing tablet, to obtain final product.
Embodiment 5 stability test result table
Stability experiment method is as follows: sample is respectively charged into Medicinal composite film bag, and under being positioned over 60 DEG C of environment, storage period is 1 month, and sampling detects its purity situation, and test-results is as shown in table 4.
Table 4 Faropenem sodium defects inspecting
From purity situation, faropenem sodium hydrate monocrystalline crystal formation under the high temperature conditions stability has significant advantage than unformed.
Claims (2)
1. faropenem sodium hydrate monocrystalline crystal formation, is characterized in that, described monocrystalline crystal formation is rhombic system, and its crystallographic axis is a=5.4998 (3), b=9.2057 (4), c=32.4371 (12); Crystal face angle is α=90 °, β=90 °, λ=90 °.
2. the preparation method of monocrystalline crystal formation as claimed in claim 1, is characterized in that, comprise the steps: addition method faropenem in purified water, be heated to more than 50 DEG C, dissolve completely to solid, stop heating, slow cooling static more than placement 48h, after separating out solid, filter, dry.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201410531418.5A CN104262360A (en) | 2014-10-10 | 2014-10-10 | Monocrystal form of faropenem sodium hydrate and preparation method thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201410531418.5A CN104262360A (en) | 2014-10-10 | 2014-10-10 | Monocrystal form of faropenem sodium hydrate and preparation method thereof |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN104262360A true CN104262360A (en) | 2015-01-07 |
Family
ID=52153971
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201410531418.5A Pending CN104262360A (en) | 2014-10-10 | 2014-10-10 | Monocrystal form of faropenem sodium hydrate and preparation method thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN104262360A (en) |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101033233A (en) * | 2006-03-07 | 2007-09-12 | 江苏正大天晴药业股份有限公司 | Faropenem sodium crystallization and preparation method thereof |
| CN101914098A (en) * | 2010-07-20 | 2010-12-15 | 深圳市海滨制药有限公司 | Preparation method of Meropenem trihydrate crystals |
| CN103588786A (en) * | 2013-11-21 | 2014-02-19 | 黄冈鲁班药业有限公司 | Purification method of faropenem sodium hydrate |
-
2014
- 2014-10-10 CN CN201410531418.5A patent/CN104262360A/en active Pending
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101033233A (en) * | 2006-03-07 | 2007-09-12 | 江苏正大天晴药业股份有限公司 | Faropenem sodium crystallization and preparation method thereof |
| CN101914098A (en) * | 2010-07-20 | 2010-12-15 | 深圳市海滨制药有限公司 | Preparation method of Meropenem trihydrate crystals |
| CN103588786A (en) * | 2013-11-21 | 2014-02-19 | 黄冈鲁班药业有限公司 | Purification method of faropenem sodium hydrate |
Non-Patent Citations (2)
| Title |
|---|
| 周庆英等: "新型青霉素烯类康生物法罗培南钠", 《中国新药杂志》 * |
| 王彬等: "法罗培南钠的波谱学数据与结构确证", 《波谱学杂志》 * |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JP6321853B2 (en) | Polymorphic and pseudopolymorphic forms of pharmaceutical compounds | |
| JP2021105043A (en) | Non-solvate crystal, production method thereof, and application thereof | |
| CN102321019A (en) | The crystalline form of quinoline compound and working method thereof | |
| CN103524532B (en) | Ceftizoxime sodium compound crystal form, and preparing method and pharmaceutical preparation thereof | |
| CN103467494B (en) | Novel crystal form of cefdinir and preparation method thereof | |
| Colombo et al. | Crystal chemistry of the antibiotic doripenem | |
| CN104262360A (en) | Monocrystal form of faropenem sodium hydrate and preparation method thereof | |
| CA2656711A1 (en) | Novel hydrate form of moxifloxacin monohydrochloride | |
| CN103520120B (en) | A kind of L-084 composition granule | |
| EP1934231A1 (en) | Crystalline sodium salt of cephalosporin antibiotic | |
| CN102942577A (en) | Cefoxitin sodium compound-containing pharmaceutical composition | |
| CN110256464B (en) | Method for preparing cefditoren pivoxil ring-opening dimer | |
| CN102731507B (en) | Tebipenem crystal forms, their preparation method and application in preparation of medicines | |
| US8871927B2 (en) | Method for purifying Ceftizoxime sodium | |
| CN104530082A (en) | Cefathiamidine compound | |
| CN106167499A (en) | Vinyl cephalosporins derivatives containing pyridinium ion and its preparation method and application | |
| CN105541871B (en) | A kind of cefmetazole crystal-form compound and preparation method thereof | |
| CN111018890A (en) | Cefathiamidine acetone hydrosolvent single crystal and preparation method thereof | |
| TW201811338A (en) | Crystal form of oritavancin diphosphate, and preparation method and use thereof | |
| CN101973868B (en) | Sodium phenylbutyrate crystal I and preparation method thereof | |
| CN102757334B (en) | Sodium phenylbutyrate type II crystal and preparation method thereof | |
| CN105622728A (en) | Stable oritavancin compound | |
| CN102659644A (en) | Crystal forms of 2-aminoethyl sulfonic acid and preparation processes for crystal forms | |
| CN105646583A (en) | Stable ceftaroline compound | |
| CN102363621A (en) | Cefminox sodium hexahydrate, preparation method thereof and pharmaceutical composition containing hexahydrate |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| RJ01 | Rejection of invention patent application after publication | ||
| RJ01 | Rejection of invention patent application after publication |
Application publication date: 20150107 |