CN105153196A - New flucloxacillin sodium crystal form as well as preparation method and application thereof - Google Patents
New flucloxacillin sodium crystal form as well as preparation method and application thereof Download PDFInfo
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- CN105153196A CN105153196A CN201510584877.4A CN201510584877A CN105153196A CN 105153196 A CN105153196 A CN 105153196A CN 201510584877 A CN201510584877 A CN 201510584877A CN 105153196 A CN105153196 A CN 105153196A
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- crystal form
- flucloxacillin
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- 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
- C07D499/21—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 with a nitrogen atom directly attached in position 6 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
- C07D499/44—Compounds with an amino radical acylated by carboxylic acids, attached in position 6
- C07D499/76—Compounds with an amino radical acylated by carboxylic acids, attached in position 6 with hetero rings directly attached to the carboxamido radical
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/425—Thiazoles
- A61K31/429—Thiazoles condensed with heterocyclic ring systems
- A61K31/43—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
- A61K31/431—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 containing further heterocyclic rings, e.g. ticarcillin, azlocillin, oxacillin
-
- 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
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- 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
Abstract
The invention discloses a new flucloxacillin sodium crystal form as well as a preparation method and an application thereof, and belongs to the field of medical technologies. An X-ray powder diffraction pattern of the new flucloxacillin sodium crystal form has a strongest diffraction peak namely I/I0=100 when 2theta=11.377 degrees; and an infrared spectrum has characteristic absorption at 792, 896, 1249, 1323, 1400, 1454, 1508, 1600, 1770, 2977 and 3367 cm<-1>. The preparation method comprises the following steps: dissolving flucloxacillin sodium into a ketone solvent, and filtering to obtain a solution A; adding an ether solvent into the solution A, stirring, and cooling to obtain a solution B; and adding an ester solvent into the solution B, stirring for crystallization, filtering, and performing vacuum drying to obtain the new crystal form. The invention also discloses the application of the new crystal form. The new crystal form is easy to dry, can effectively reduce the drying time and reduce the risk of impurity increase, and has a relatively good effect for quality control.
Description
Technical field
The present invention relates to a kind of Flucloxacillin sodium novel crystal form, preparation method and application, belong to medical art.
Background technology
Material owing to affecting by various factors, makes in molecule or intermolecular bonding mode changes when crystallization, thus molecule or atom different in lattice vacancy arrangement, form different crystalline structure.Namely same substance has two or more spatial disposition and unit cell parameters, and the phenomenon forming multiple crystal formation is called heteromorphism (polymorphism).When material is dissolved or after melting, crystalline network is destroyed, polymorphism also just disappears.
Polymorph in pharmaceuticals phenomenon extensively exists in the PRODUCTION TRAITS of solid pharmaceutical, is the one of the main reasons affecting solid pharmaceutical drug effect.Suitable, homogeneous crystal formation is conducive to the curative effect improving medicine, improves the stability of medicine, reduces drug side effect etc.The new crystal of some medicines can also develop the solid pharmaceutical made new advances.
Product crystal formation is an important factor of product drying speed, and the time of drying of different crystal formation products is likely different.In addition, drying process can affect quality product.Drying temperature is too low, will certainly extend time of drying.Ideally find a balance of drying temperature and time of drying, general selection is at a higher temperature, completes drying, and can ensure the quality of product within the time short as far as possible.
Sodium flucloxacillin, chemical name: (2S, 5R, 6R)-6-[[3-(the chloro-6-fluorophenyl of 2-)-5-methyl isophthalic acid, 2-oxazole-4-formyl] amino]-3,3-dimethyl-7-oxo-4-thia-1-azabicyclo [3.2.0] heptane-2-formic acid sodium salts.Sodium flucloxacillin is a kind of β-lactam antibitics, has the ability of wider anti-microbial activity and stronger anti-beta-lactamase, is mainly used in treating bacterial infection.
At present, due to the laws and regulations requirement controlled dissolvent residual, in the manufacturing of Sodium flucloxacillin, the dry cycle is long.Product is long-time dry under the high temperature conditions, has very large challenge to the quality of product, because time of drying is long, the product risk that at high temperature impurity increases just strengthens.The present invention is a kind of new crystal formation of unexpected acquisition in research process, and this crystal formation can shorten the time of drying of product significantly, effectively reduces the risk that product impurity increases.
Summary of the invention
First object of the present invention, is to provide a kind of Flucloxacillin sodium novel crystal form.New crystal of the present invention can shorten the time of drying of product significantly, effectively reduces the risk that product impurity increases.
The technical scheme that the present invention solves the problems of the technologies described above is as follows: a kind of Flucloxacillin sodium novel crystal form, and its X-ray powder diffraction, has the strongest diffraction peak and I/I0=100 in 2 θ=11.377 °; Infrared spectra, at 792cm
-1, 896cm
-1, 1249cm
-1, 1323cm
-1, 1400cm
-1, 1454cm
-1, 1508cm
-1, 1600cm
-1, 1770cm
-1, 2977cm
-1and 3367cm
-1there is characteristic absorbance
On the basis of technique scheme, the present invention can also do following improvement.
Further, the X-ray powder diffraction of described chlorine XiLin sodium novel crystal form in 2 θ=5.083 °, 13.121 °, 15.896 °, 19.573 °, 22.348 °, 29.413 °, 30.170 °, 39.800 ° have characteristic diffraction peak.
Second object of the present invention, is to provide the preparation method of a kind of above-mentioned Flucloxacillin sodium novel crystal form.
The technical scheme that the present invention solves the problems of the technologies described above is as follows: the preparation method of a kind of Flucloxacillin sodium novel crystal form, comprises the steps:
(1) count by weight, get 1 part of Sodium flucloxacillin, be dissolved in 5 ~ 7 parts of ketones solvents, filter, obtain solution A, control the temperature of solution A at 0 ~ 15 DEG C;
(2) count by weight, get 2 ~ 3.6 parts of ether solvents, join in step (1) gained solution A, stir, slow cooling, to-5 ~-15 DEG C, obtains solution B;
(3) count by weight, get 1.2 ~ 3.4 parts of esters solvents, join in step (2) gained solution B, stirring and crystallizing 2h in 2.5 ~ 4h, after filtration, vacuum decompression is dry, obtains described Flucloxacillin sodium novel crystal form.
On the basis of technique scheme, the present invention can also do following improvement.
Further, step (1) described ketones solvent is acetone.
Further, step (2) described ether solvent is one or both in isopropyl ether, methyl tertiary butyl ether, and the time of described stirring is 30min.
Further, step (3) described esters solvent is one or both in methyl acetate, ethyl acetate.
Further, the pressure of the described vacuum decompression drying of step (3) is-0.08 ~-0.09MPa, and temperature is 45 ~ 60 DEG C.
In addition, the present invention also provides the application of above-mentioned Flucloxacillin sodium novel crystal form, the application in the new brilliant medicine infecting caused by the responsive gram-positive microorganism for the treatment of of described Sodium flucloxacillin.
On the basis of technique scheme, the present invention can also do following improvement.
Further, described responsive gram-positive microorganism comprises product enzyme staphylococcus and suis.
Further, described infection comprises the preventing infection in the infection of penicillin resistant caused by Staphylococcus aureus, Skin and soft tissue infection, respiratory system infection, urinary tract infection, septicemia, major surgery process.
The invention has the beneficial effects as follows:
1. adopt the new crystal that preparation method of the present invention obtains, easily dry, effectively can reduce the time of product drying, effectively reduce the risk that product impurity increases, have good effect for the quality controlling product.
2. the present invention can shorten the time of product drying, is therefore conducive to the production cost controlling product.
3. the product that obtains of the present invention, granularity is comparatively large, is conducive to the production carrying out preparation.
4. preparation method of the present invention is simple, and wide market, is conducive to suitability for industrialized production.
Accompanying drawing explanation
Fig. 1 is the infared spectrum of embodiments of the invention 1.
Fig. 2 is the crystal powder diffracting spectrum of embodiments of the invention 1.
Fig. 3 is the thermogravimetric-difference quotient thermogravimetric collection of illustrative plates of embodiments of the invention 1.
Fig. 4 is the polarizing microscope collection of illustrative plates of embodiments of the invention 1.
Fig. 5 is the polarizing microscope collection of illustrative plates of comparative example 1 of the present invention.
Embodiment
Be described principle of the present invention and feature below in conjunction with accompanying drawing, example, only for explaining the present invention, is not intended to limit scope of the present invention.
Embodiment 1
(1) get 50g Sodium flucloxacillin, be dissolved in 250g acetone, filter, obtain solution A, control the temperature of solution A at 0 DEG C;
(2) get 180g isopropyl ether, join in step (1) gained solution A, stir 30min, be cooled to-5 DEG C, obtain solution B;
(3) get 100g methyl acetate, join in step (2) gained solution B in 3h, after dropwising, stirring and crystallizing 2h, after filtration, in 50 DEG C, the drying of-0.08 ~-0.09MPa vacuum decompression, obtains described Flucloxacillin sodium novel crystal form.
As shown in Figure 1, in infrared spectra, at 792cm
-1, 896cm
-1, 1249cm
-1, 1323cm
-1, 1400cm
-1, 1454cm
-1, 1508cm
-1, 1600cm
-1, 1770cm
-1, 2977cm
-1and 3367cm
-1there is characteristic absorbance.
Wherein, at 1454cm
-1, 1508cm
-1and 1600cm
-1there is phenyl ring skeletal vibration, 792cm
-1for three adjacent=C-H out-of-plane deformation vibrations on phenyl ring, 896cm
-1for N=O stretching vibration on thiophene oxime ring, 1249cm
-1for C=O stretching vibration on thiophene oxime ring, 1323cm
-1for-CH in C-C skeletal vibration and thiophene oxime ring
3c-H asymmetric bending vibration coupling, 1400cm
-1for-CH on hydrogenation thiazole ring
3cH asymmetric bending vibration, 1600cm
-1for phenyl ring skeletal vibration to be coupled with C=N stretching vibration peak, 1770cm
-1for C=O stretching vibration on beta-lactam nucleus, 2977cm
-1for CH
3c-H asymmetrical stretching vibration, 3367cm
-1for N-H stretching vibration.
As shown in Figure 2, the strongest absorption peak (I/I0=100) is had in 2 θ=11.377 °, in 2 θ=5.083 °, also there is characteristic diffraction peak at 13.121 °, 15.896 °, 19.573 °, 22.348 °, 29.413 °, 30.170 °, 39.800 ° places, and concrete numerical value is as shown in table 1.
Table 1 powder diffraction data table
Shown in Fig. 3 thermogravimetric-difference quotient thermogravimetric collection of illustrative plates, Flucloxacillin of the present invention sodium crystal is containing the crystal water of 1 molecule, and crystal water accounts for 3.21% of total mass, decomposes at about 180 DEG C.
As shown in Figure 4, product of the present invention is crystal.
Embodiment 2
(1) get 50g Sodium flucloxacillin, be dissolved in 350g acetone, filter, obtain solution A, control the temperature of solution A at 9 DEG C;
(2) get 130g isopropyl ether, join in step (1) gained solution A, stir 30min, be cooled to-10 DEG C, obtain solution B;
(3) get 170g methyl acetate, join in step (2) gained solution B in 4h, after dropwising, stirring and crystallizing 2h, after filtration, in 60 DEG C, the drying of-0.08 ~-0.09MPa vacuum decompression, obtains described Flucloxacillin sodium novel crystal form.
Embodiment 3
(1) get 50g Sodium flucloxacillin, be dissolved in 350g acetone, filter, obtain solution A, control the temperature of solution A at 15 DEG C;
(2) get 100g isopropyl ether, join in step (1) gained solution A, stir 30min, be cooled to-10 DEG C, obtain solution B;
(3) get 120g ethyl acetate, join in step (2) gained solution B in 3.5h, after dropwising, stirring and crystallizing 2h, after filtration, in 45 DEG C, the drying of-0.08 ~ 0.09MPa vacuum decompression, obtains described Flucloxacillin sodium novel crystal form.
Embodiment 4
(1) get 50g Sodium flucloxacillin, be dissolved in 300g acetone, filter, obtain solution A, control the temperature of solution A at 5 DEG C;
(2) get 130g isopropyl ether, join in step (1) gained solution A, stir 30min, be cooled to-15 DEG C, obtain solution B;
(3) get 100g ethyl acetate, join in step (2) gained solution B in 3h, after dropwising, stirring and crystallizing 2h, after filtration, in 55 DEG C, the drying of-0.08 ~ 0.09MPa vacuum decompression, obtains described Flucloxacillin sodium novel crystal form.
Embodiment 5
(1) get 50g Sodium flucloxacillin, be dissolved in 300g acetone, filter, obtain solution A, control the temperature of solution A at 5 DEG C;
(2) get 130g methyl tertiary butyl ether, join in step (1) gained solution A, stir 30min, be cooled to-15 DEG C, obtain solution B;
(3) get 100g ethyl acetate, join in step (2) gained solution B in 3h, after dropwising, stirring and crystallizing 2h, after filtration, in 48 DEG C, the drying of-0.08 ~ 0.09MPa vacuum decompression, obtains described Flucloxacillin sodium novel crystal form.
Embodiment 6
(1) get 50g Sodium flucloxacillin, be dissolved in 250g acetone, filter, obtain solution A, control the temperature of solution A at 0 DEG C;
(2) get 150g methyl tertiary butyl ether, join in step (1) gained solution A, stir 30min, be cooled to-10 DEG C, obtain solution B;
(3) get 60g ethyl acetate, join in step (2) gained solution B in 2.5h, after dropwising, stirring and crystallizing 2h, after filtration, in 60 DEG C, the drying of-0.08 ~ 0.09MPa vacuum decompression, obtains described Flucloxacillin sodium novel crystal form.
Comparative example 1
Get 50g Sodium flucloxacillin, be dissolved in 250g ethyl acetate, filter, the temperature of solution is down to 5 DEG C, stir 2h, be then cooled to-10 DEG C, control temperature at-10 DEG C, stirring and crystallizing 2h, filter, in 60 DEG C, the drying of-0.08 ~-0.09MPa vacuum decompression, obtain Flucloxacillin sodium crystal.
As shown in Figure 5, product crystal prepared by the method is less, and from the result (table 2) of drying, the time of drying that the product needed of gained is longer, the quality control for production cost and product is disadvantageous.
Comparative example 2
Get 50g Sodium flucloxacillin, be dissolved in 250g methyl acetate, filter, the temperature of solution is down to 5 DEG C, stir 2h, be then cooled to-10 DEG C, control temperature at-10 DEG C, stirring and crystallizing 2h, filter, in 60 DEG C, the drying of-0.08 ~-0.09MPa vacuum decompression, obtain Flucloxacillin sodium crystal.
After embodiment 1-6 and comparative example 1-2 drying terminate, Key Quality Con trolling index, the situation that namely organic impurity and esters solvent remain contrasts, as shown in table 2.
The dry Comparative result of table 2
Official requirement, the Control of Impurities limit of this product is single assorted≤1%, total assorted≤5%, organic solvent used belongs to three kind solvents, and the requirement of pharmacopeia controls solvent used residual quantity in the product to require≤0.5%.Facts have proved, in organic solvent used, esters solvent is the most difficult to be removed from product, so select esters solvent as detection and control criterion.
As shown in Table 2, the product of embodiment 1-6 method gained is under equal drying conditions, control to not being as the criterion higher than the limit of laws and regulations requirement with dissolvent residual, the time that the time of drying of embodiment 1-6 is significantly used than the drying of comparative example 1-2 is few, and the impurity level of the product of embodiment 1-6 gained is significantly low than the impurity level of the product of comparative example 1-2, quality will be got well.So from industrial production, embodiment 1-6 method shows better utilised and is worth.
The foregoing is only preferred embodiment of the present invention, not in order to limit the present invention, within the spirit and principles in the present invention all, any amendment done, equivalent replacement, improvement etc., all should be included within protection scope of the present invention.
Claims (10)
1. a Flucloxacillin sodium novel crystal form, is characterized in that, its X-ray powder diffraction, has the strongest diffraction peak and I/I0=100 in 2 θ=11.377 °; Infrared spectra, at 792cm
-1, 896cm
-1, 1249cm
-1, 1323cm
-1, 1400cm
-1, 1454cm
-1, 1508cm
-1, 1600cm
-1, 1770cm
-1, 2977cm
-1and 3367cm
-1there is characteristic absorbance.
2. a kind of Flucloxacillin according to claim 1 sodium novel crystal form, it is characterized in that, the X-ray powder diffraction of described chlorine XiLin sodium novel crystal form in 2 θ=5.083 °, 13.121 °, 15.896 °, 19.573 °, 22.348 °, 29.413 °, 30.170 °, 39.800 ° have characteristic diffraction peak.
3. a preparation method for Flucloxacillin sodium novel crystal form, is characterized in that, comprises the steps:
(1) count by weight, get 1 part of Sodium flucloxacillin, be dissolved in 5 ~ 7 parts of ketones solvents, filter, obtain solution A, control the temperature of solution A at 0 ~ 15 DEG C;
(2) count by weight, get 2 ~ 3.6 parts of ether solvents, join in step (1) gained solution A, stir, slow cooling, to-5 ~-15 DEG C, obtains solution B;
(3) count by weight, get 1.2 ~ 3.4 parts of esters solvents, join in step (2) gained solution B, stirring and crystallizing 2h in 2.5 ~ 4h, after filtration, vacuum decompression is dry, obtains described Flucloxacillin sodium novel crystal form.
4. the preparation method of a kind of Flucloxacillin according to claim 3 sodium novel crystal form, is characterized in that, step (1) described ketones solvent is acetone.
5. the preparation method of a kind of Flucloxacillin according to claim 3 sodium novel crystal form, is characterized in that, step (2) described ether solvent is isopropyl ether or methyl tertiary butyl ether, and the time of described stirring is 30min.
6. the preparation method of a kind of Flucloxacillin according to claim 3 sodium novel crystal form, is characterized in that, step (3) described esters solvent is methyl acetate or ethyl acetate.
7. the preparation method of a kind of Flucloxacillin according to claim 3 sodium novel crystal form, is characterized in that, the pressure of the described vacuum decompression drying of step (3) is-0.08 ~-0.09MPa, and temperature is 45 ~ 60 DEG C.
8. an application for the Flucloxacillin sodium novel crystal form as described in any one of claim 1-2, is characterized in that, the application in the new brilliant medicine infecting caused by the responsive gram-positive microorganism for the treatment of of described Sodium flucloxacillin.
9. the application of a kind of Flucloxacillin according to claim 8 sodium novel crystal form, is characterized in that, described responsive gram-positive microorganism comprises product enzyme staphylococcus and suis.
10. the application of a kind of Flucloxacillin according to claim 8 sodium novel crystal form, it is characterized in that, described infection comprises the preventing infection in the infection of penicillin resistant caused by Staphylococcus aureus, Skin and soft tissue infection, respiratory system infection, urinary tract infection, septicemia, major surgery process.
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Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0273156A2 (en) * | 1986-12-23 | 1988-07-06 | Giovanni Bonfanti | Method for producing pure crystalline products |
| CN102285998A (en) * | 2011-06-17 | 2011-12-21 | 桂林理工大学 | Preparation method of amorphous and three polymorphic substances of flucloxacillin sodium |
| CN102351882A (en) * | 2011-09-20 | 2012-02-15 | 海南美兰史克制药有限公司 | Flucloxacillin sodium compound and preparation method thereof |
| CN102702227A (en) * | 2012-06-12 | 2012-10-03 | 河北华日药业有限公司 | Preparation method for flucloxacillin sodium |
-
2015
- 2015-09-15 CN CN201510584877.4A patent/CN105153196B/en active Active
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0273156A2 (en) * | 1986-12-23 | 1988-07-06 | Giovanni Bonfanti | Method for producing pure crystalline products |
| CN102285998A (en) * | 2011-06-17 | 2011-12-21 | 桂林理工大学 | Preparation method of amorphous and three polymorphic substances of flucloxacillin sodium |
| CN102351882A (en) * | 2011-09-20 | 2012-02-15 | 海南美兰史克制药有限公司 | Flucloxacillin sodium compound and preparation method thereof |
| CN102702227A (en) * | 2012-06-12 | 2012-10-03 | 河北华日药业有限公司 | Preparation method for flucloxacillin sodium |
Non-Patent Citations (2)
| Title |
|---|
| 周肖寅 等: ""不同晶型氟氯西林钠在水中溶解度的测定和关联"", 《中国抗生素杂志》 * |
| 辛小娟 等: ""阿莫西林氟氯西林钠胶囊与阿莫西林/克拉维酸钾片随机对照治疗呼吸道细菌性感染75例"", 《重庆医科大学学报》 * |
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