CN106496272A - A kind of crystal formation A of oxazolidinone antibacterial medicine magnesium salts and its preparation method and application - Google Patents
A kind of crystal formation A of oxazolidinone antibacterial medicine magnesium salts and its preparation method and application Download PDFInfo
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- CN106496272A CN106496272A CN201610837718.5A CN201610837718A CN106496272A CN 106496272 A CN106496272 A CN 106496272A CN 201610837718 A CN201610837718 A CN 201610837718A CN 106496272 A CN106496272 A CN 106496272A
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- crystal formation
- magnesium salts
- oxazolidinone antibacterial
- antibacterial medicine
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- 239000003814 drug Substances 0.000 title claims abstract description 64
- 230000000844 anti-bacterial effect Effects 0.000 title claims abstract description 48
- 159000000003 magnesium salts Chemical class 0.000 title claims abstract description 45
- IZXIZTKNFFYFOF-UHFFFAOYSA-N 2-Oxazolidone Chemical compound O=C1NCCO1 IZXIZTKNFFYFOF-UHFFFAOYSA-N 0.000 title claims abstract description 44
- 230000015572 biosynthetic process Effects 0.000 title claims abstract description 43
- 239000013078 crystal Substances 0.000 title claims abstract description 43
- 238000002360 preparation method Methods 0.000 title claims abstract description 20
- 230000003115 biocidal effect Effects 0.000 claims abstract description 6
- 159000000000 sodium salts Chemical class 0.000 claims description 30
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 23
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical group [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 claims description 14
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical group OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 12
- 239000003960 organic solvent Substances 0.000 claims description 10
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 9
- 238000002425 crystallisation Methods 0.000 claims description 9
- 230000008025 crystallization Effects 0.000 claims description 9
- 238000001228 spectrum Methods 0.000 claims description 9
- 229910052943 magnesium sulfate Inorganic materials 0.000 claims description 7
- 235000019341 magnesium sulphate Nutrition 0.000 claims description 7
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical group CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims description 6
- TWRXJAOTZQYOKJ-UHFFFAOYSA-L Magnesium chloride Chemical compound [Mg+2].[Cl-].[Cl-] TWRXJAOTZQYOKJ-UHFFFAOYSA-L 0.000 claims description 6
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 6
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 claims description 3
- 229910001629 magnesium chloride Inorganic materials 0.000 claims description 3
- 231100000252 nontoxic Toxicity 0.000 claims description 3
- 230000003000 nontoxic effect Effects 0.000 claims description 3
- 239000002904 solvent Substances 0.000 claims description 3
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 3
- 238000007865 diluting Methods 0.000 claims description 2
- 239000008194 pharmaceutical composition Substances 0.000 abstract description 2
- 238000002441 X-ray diffraction Methods 0.000 abstract 1
- 239000007787 solid Substances 0.000 description 9
- 238000003756 stirring Methods 0.000 description 8
- 229940079593 drug Drugs 0.000 description 7
- 238000000034 method Methods 0.000 description 7
- 238000000634 powder X-ray diffraction Methods 0.000 description 7
- 239000012266 salt solution Substances 0.000 description 7
- 239000000243 solution Substances 0.000 description 7
- 230000003068 static effect Effects 0.000 description 7
- 238000001291 vacuum drying Methods 0.000 description 6
- 238000000967 suction filtration Methods 0.000 description 5
- 230000000694 effects Effects 0.000 description 4
- 206010034133 Pathogen resistance Diseases 0.000 description 3
- 150000003839 salts Chemical class 0.000 description 3
- 241000894006 Bacteria Species 0.000 description 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
- 239000002253 acid Substances 0.000 description 2
- 150000001875 compounds Chemical class 0.000 description 2
- 238000001816 cooling Methods 0.000 description 2
- 238000001514 detection method Methods 0.000 description 2
- 238000005516 engineering process Methods 0.000 description 2
- 229960002337 magnesium chloride Drugs 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 238000011056 performance test Methods 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- 238000012827 research and development Methods 0.000 description 2
- 239000013557 residual solvent Substances 0.000 description 2
- 238000013112 stability test Methods 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 238000012360 testing method Methods 0.000 description 2
- 108010010803 Gelatin Proteins 0.000 description 1
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- 150000008064 anhydrides Chemical class 0.000 description 1
- 229940088710 antibiotic agent Drugs 0.000 description 1
- 159000000007 calcium salts Chemical class 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 239000011248 coating agent Substances 0.000 description 1
- 238000002447 crystallographic data Methods 0.000 description 1
- QGBSISYHAICWAH-UHFFFAOYSA-N dicyandiamide Chemical compound NC(N)=NC#N QGBSISYHAICWAH-UHFFFAOYSA-N 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- 239000000796 flavoring agent Substances 0.000 description 1
- 235000013355 food flavoring agent Nutrition 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 239000012535 impurity Substances 0.000 description 1
- 238000009413 insulation Methods 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 229940050906 magnesium chloride hexahydrate Drugs 0.000 description 1
- DHRRIBDTHFBPNG-UHFFFAOYSA-L magnesium dichloride hexahydrate Chemical compound O.O.O.O.O.O.[Mg+2].[Cl-].[Cl-] DHRRIBDTHFBPNG-UHFFFAOYSA-L 0.000 description 1
- GVALZJMUIHGIMD-UHFFFAOYSA-H magnesium phosphate Chemical compound [Mg+2].[Mg+2].[Mg+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O GVALZJMUIHGIMD-UHFFFAOYSA-H 0.000 description 1
- 229960002261 magnesium phosphate Drugs 0.000 description 1
- 229910000157 magnesium phosphate Inorganic materials 0.000 description 1
- 239000004137 magnesium phosphate Substances 0.000 description 1
- 235000010994 magnesium phosphates Nutrition 0.000 description 1
- 230000008520 organization Effects 0.000 description 1
- 235000010987 pectin Nutrition 0.000 description 1
- 229920001277 pectin Polymers 0.000 description 1
- 239000001814 pectin Substances 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 238000012216 screening Methods 0.000 description 1
- 239000011343 solid material Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 238000003860 storage Methods 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
- C07F9/6561—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom containing systems of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring or ring system, with or without other non-condensed hetero rings
-
- 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
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Biochemistry (AREA)
- General Health & Medical Sciences (AREA)
- Molecular Biology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention discloses the characteristic peak that a kind of crystal formation A of oxazolidinone antibacterial medicine magnesium salts and its preparation method and application, the crystal formation A are determined comprising following 2 θ angles of reflection in X x ray diffraction collection of illustrative plates：12.6±0.2°、16.8±0.2°、17.4±0.2°、18.9±0.2°、20.7±0.2°、21.5±0.2°、22.7±0.2°、24.3±0.2°、24.9±0.2°、26.4±0.2°、27.3±0.2°、28.2±0.2°、31.2±0.2°.Crystal formation A good stabilities, dissolvent residual are low, can be used to prepare pharmaceutical composition, and there is in antibiotic medicine is prepared important application value.
Description
Technical field
The invention belongs to field of medicaments, and in particular to a kind of crystal formation A of oxazolidinone antibacterial medicine magnesium salts and its preparation
Methods and applications.
Background technology
In recent years, the drug-fast bacteria of all kinds of antibacterials develops the health for seriously threatening the mankind rapidly, 2011
The World Health Organization alerts the world and will enter " antibiotic epoch afterwards " for this.Various countries have appreciated that research and development novel antibacterial medicine
Importance, the U.S. were have approved in 2012《FDA safety and innovation bill》, its Part VIII is《Encourage exploitation antibiotic method
Case》(GAIN bills).Country defended 14 ministries and commissions such as planning commission and combined and issues this year《With regard to printing and distributing the action of containment bacterial resistance country
The notice of plan (2016-2020)》, the challenge that reply bacterial resistance brings is by height of the lifting to State-level first, work
For resisting important measures of bacterial resistance problem, the research and development for supporting and encourageing novel antibacterial medicine become focus again.
European patent EP 2940024A1 discloses a kind of new oxazolidinone antibacterial medicine, compound structure such as formula (1)
Shown：
Result of study shows that there is the oxazolidinone antibacterial medicine shown in formula (1) antibacterial higher compared with similar drugs to live
Property, especially resist many drug-fast bacteria activity, refer to described in patent EP2940024A1.The medicinal forms of formula (1) medicine include dissociating
Sour and its pharmaceutically acceptable salt, the such as salt such as sodium salt, magnesium salts and calcium salt.
It is well known that in solid drugs generally existing polymorphism, crystal formation is the weight for affecting drug quality and curative effect
Want one of factor.In recent years, domestic pharmacy corporation starts gradually to pay attention to the research to drug crystal forms, understands the crystal formation of solid drugs
Contribute to solving following point：Ensure the stability of solid material medicine and preparation in production and transport storage process；By polycrystalline
The bioavilability screening of type medicine, promotes the curative effect of medicine；Ensure that the bulk drug of each production batch is consistent with preparation crystal formation
Property.
European patent EP 2940024A1 discloses the preparation method of formula (1) free acid and formula (3) sodium salt, but and is not disclosed
The preparation method of formula (2) magnesium salts (M=Mg) and its crystal formation.We have found that the free acid and sodium salt prepared according to this compound patent
Amorphous products are, and amorphous products dissolvent residual is easily exceeded, stability is relatively poor, it is therefore necessary to develop formula
(1) the crystal formation product of officinal salt.
Content of the invention
The invention provides a kind of crystal formation A of oxazolidinone antibacterial medicine magnesium salts and its preparation method and application, the crystalline substance
, compared with unformed, with more preferable stability, organic solvent residual is lower for type A.
The present invention is achieved in the following ways：
A kind of crystal formation A of oxazolidinone antibacterial medicine magnesium salts, includes following 2 θ angles of reflection in X-ray diffracting spectrum
The characteristic peak of measure：12.6±0.2°、16.8±0.2°、17.4±0.2°、18.9±0.2°、20.7±0.2°、21.5±
0.2°、22.7±0.2°、24.3±0.2°、24.9±0.2°、26.4±0.2°、27.3±0.2°、28.2±0.2°、31.2±
0.2°.
The structural formula such as formula (2) of the crystal formation A of described oxazolidinone antibacterial medicine magnesium salts：
Stability test and residual solvent detection show, are prepared into according to the method for EP2940024A1 relative to applicant
The oxazolidinone antibacterial medicine sodium salt for arriving and unformed magnesium salts, the crystal formation A of formula (2) magnesium salts have more preferable stability and
Lower dissolvent residual.
Preferably, the X-ray diffracting spectrum of described crystal formation A is as shown in Figure 1.
The present invention also provides a kind of preparation method of the crystal formation A of oxazolidinone antibacterial medicine magnesium salts described above, including
Following steps：
1) will be soluble in water for oxazolidinone antibacterial medicine sodium salt, and organic solvent diluting is added, obtain solution I；Described
Organic solvent be acetone, acetonitrile, tetrahydrofuran, dioxane, C1～C3One kind in alkylol；
2) solution II is obtained by soluble in water for inorganic magnesium salt, solution II is added in solution I, stand crystallization, filter, do
Dry, obtain described crystal formation A.
Wherein, described oxazolidinone antibacterial medicine sodium salt may be referred to the preparation in European patent EP 2940024A1
Method is prepared, shown in its structural formula such as formula (3)：
The reaction equation of the preparation method is as follows：
We by research find, if dicyandiamide solution is simple water, the magnesium salts for obtaining be amorphous products, crystal formation A
Product can only be obtained in the mixed system of water and organic solvent, and organic solvent and water must be controlled certain in solution I
In proportion, otherwise sodium salt is easily separated out or obtains the amorphous products of magnesium salts.
Preferably, described oxazolidinone antibacterial medicine sodium salt enantiomeric purity is more than 99%, 6 for containing are non-right
Reflect isomers 1% is less than in interior impurity summation.
Preferably, described oxazolidinone antibacterial medicine sodium salt enantiomeric purity is more than 99.5%.
Preferably, described organic solvent I is methyl alcohol.
Preferably, organic solvent is 0.5～3 with the volume ratio of water in described solution I.
Preferably, described inorganic magnesium salt is magnesium sulfate or magnesium chloride, can be anhydride or hydrate.
The present invention also provides a kind of crystal formation A of oxazolidinone antibacterial medicine magnesium salts described above and is preparing antibiotic medicine
In application.
Preferably, described medicine comprising oxazolidinone antibacterial medicine magnesium salts crystal formation A and one or more can
Medicinal inert non-toxic carrier.Described inert non-toxic carrier can be selected according to the existing knowledge of those skilled in the art
Select, including diluent pharmaceutically used, flavouring agent, solubilizer, lubricant and coating agent etc., such as magnesium phosphate, smoothers sugar,
Lactose, pectin, starch and gelatin etc..
Compared with the existing technology, the crystal formation A of the oxazolidinone antibacterial medicine magnesium salts is very stable in environment around, and
Solvent residual amount is little, can be used for preparing pharmaceutical composition；In the process parameters range described in the preparation method, repeat multiple
Batch, reappearance are fabulous.
Description of the drawings
Fig. 1 is the X-ray diffracting spectrum of the crystal formation A of oxazolidinone antibacterial medicine magnesium salts prepared by embodiment 1；
Fig. 2 is the X-ray diffracting spectrum of oxazolidinone antibacterial medicine magnesium salts amorphous products prepared by embodiment 7.
Specific embodiment
With reference to the particular that the following example illustrates the present invention, these embodiments are to illustrate the present invention, and
The non-restriction present invention by any way.
The oxazolidinone antibacterial medicine sodium salt of formula (3) is synthesized by European patent EP 2940024A1.
Embodiment 1
Formula (3) sodium salt (10.43g, 0.02mol) is dissolved in water (50mL) under room temperature, adds methyl alcohol (25mL) stirring.
Magnesium sulfate (2.41g, 0.02mol) is dissolved in water (50mL), is added in above-mentioned sodium salt solution.Static crystallization, suction filtration, vacuum
Dry, gained solid carries out powder x-ray diffraction, as a result as shown in Figure 1.
Embodiment 2
Formula (3) sodium salt (10.43g, 0.02mol) is dissolved in water (50mL), 60 DEG C is warmed up to, is added methyl alcohol
(150mL) stir.Magnesium sulfate 7 hydrate (4.93g, 0.02mol) is dissolved in water (50mL), above-mentioned sodium salt solution is added to
In, 60 DEG C of stirrings are incubated 1 hour.Cooling, static crystallization, suction filtration, vacuum drying, gained solid carry out powder x-ray diffraction.
Embodiment 3
Formula (3) sodium salt (10.43g, 0.02mol) is dissolved in water (50mL) under room temperature, adds tetrahydrofuran (35mL)
Stirring.Magnesium chloride (1.91g, 0.02mol) is dissolved in water (50mL), is added in above-mentioned sodium salt solution.Static crystallization, takes out
Filter, vacuum drying, gained solid carry out powder x-ray diffraction.
Embodiment 4
Formula (3) sodium salt (10.43g, 0.02mol) is dissolved in water (50mL), 70 DEG C are warmed up to, acetonitrile (75mL) is added
Stirring.Magnesium chloride hexahydrate (4.07g, 0.02mol) is dissolved in water (50mL), is added in above-mentioned sodium salt solution, 70 DEG C
Stirring insulation 1 hour.Cooling, static crystallization, suction filtration, vacuum drying, gained solid carry out powder x-ray diffraction.
Embodiment 5
Formula (3) sodium salt (10.43g, 0.02mol) is dissolved in water (50mL) under room temperature, adds dioxane (30mL)
Stirring.Magnesium sulfate (2.41g, 0.02mol) is dissolved in water (50mL), is added in above-mentioned sodium salt solution.Static crystallization, takes out
Filter, vacuum drying, gained solid carry out powder x-ray diffraction.
Embodiment 6
Formula (3) sodium salt (10.43g, 0.02mol) is dissolved in water (50mL) under room temperature, adds ethanol (50mL) stirring.
Magnesium sulfate 7 hydrate (4.93g, 0.02mol) is dissolved in water (50mL), is added in above-mentioned sodium salt solution.Static crystallization,
Suction filtration, vacuum drying, gained solid carry out powder x-ray diffraction.
Embodiment 7
Formula (3) sodium salt (10.43g, 0.02mol) is dissolved in water (50mL) under room temperature.Again by magnesium sulfate (2.41g,
0.02mol) it is dissolved in water (50mL), is added in above-mentioned sodium salt solution.Static crystallization, suction filtration, vacuum drying, gained solid enter
Row powder x-ray diffraction, as a result as shown in Figure 2.
Performance test 1X- ray Powder Diffraction pattern：
Determining instrument：EMPYREAN type diffractometers, PANALYTICAL
Condition determination：
Fig. 1 is the X-ray diffracting spectrum of the crystal formation A of oxazolidinone antibacterial medicine magnesium salts prepared by embodiment 1, determines
Data are listed in table 1.
The X- diffraction data of the crystal formation A of 1 oxazolidinone antibacterial medicine magnesium salts of table
The X-ray diffracting spectrum and Fig. 1 of the crystal formation A of the oxazolidinone antibacterial medicine magnesium salts prepared by embodiment 2～6
Identical.Fig. 2 is the unformed X-ray diffracting spectrum of oxazolidinone antibacterial medicine magnesium salts prepared by embodiment 7.
The crystal formation A and magnesium salts of 2 oxazolidinone antibacterial medicine magnesium salts of performance test are unformed and press European patent
EP2940024A1 synthesis oxazolidinone antibacterial medicine sodium salt mass ratio compared with
According to four general rules ＜ of Chinese Pharmacopoeia version in 2015,0861 residual solvent determination method ＞ and 9001 bulk drug of guideline ＜
Thing and crystalline substance of the preparation stability test direction principle ＞ relevant regulations to oxazolidinone antibacterial medicine magnesium salts obtained in embodiment 1
Type A and oxazolidinone antibacterial medicine magnesium salts obtained in embodiment 7 unformed and synthesize by European patent EP 2940024A1
Oxazolidinone antibacterial medicine sodium salt carry out dissolvent residual detection and accelerated test, as a result such as table 2：
2 magnesium salts crystal formation A of table and magnesium salts is unformed and the mass ratio of sodium salt compared with
Result of the test shows, the magnesium salts crystal formation A that the present processes are obtained no matter in terms of stability or dissolvent residual,
Effect is all substantially improved.
Claims (10)
1. a kind of crystal formation A of oxazolidinone antibacterial medicine magnesium salts, it is characterised in that comprising following in X-ray diffracting spectrum
The characteristic peak that 2 θ angles of reflection are determined：12.6±0.2°、16.8±0.2°、17.4±0.2°、18.9±0.2°、20.7±0.2°、
21.5±0.2°、22.7±0.2°、24.3±0.2°、24.9±0.2°、26.4±0.2°、27.3±0.2°、28.2±0.2°、
31.2±0.2°.
2. the crystal formation A of oxazolidinone antibacterial medicine magnesium salts according to claim 1, it is characterised in that described crystal formation A
X-ray diffracting spectrum as shown in Figure 1.
3. a kind of preparation method of the crystal formation A of oxazolidinone antibacterial medicine magnesium salts as claimed in claim 1 or 2, its feature
It is, comprises the following steps：
1) will be soluble in water for oxazolidinone antibacterial medicine sodium salt, and organic solvent diluting is added, obtain solution I；Described has
Machine solvent is acetone, acetonitrile, tetrahydrofuran, dioxane, C1～C3One kind in alkylol；
2) solution II is obtained by soluble in water for inorganic magnesium salt, solution II is added in solution I, stand crystallization, filter, dry,
Obtain described crystal formation A.
4. the preparation method of the crystal formation A of oxazolidinone antibacterial medicine magnesium salts according to claim 3, it is characterised in that
Described oxazolidinone antibacterial medicine sodium salt enantiomeric purity is more than 99%, and 6 for containing diastereoisomer is interior miscellaneous
Matter summation is less than 1%.
5. the preparation method of the crystal formation A of oxazolidinone antibacterial medicine magnesium salts according to claim 4, it is characterised in that
Described oxazolidinone antibacterial medicine sodium salt enantiomeric purity is more than 99.5%.
6. the preparation method of the crystal formation A of oxazolidinone antibacterial medicine magnesium salts according to claim 3, it is characterised in that
Described organic solvent is methyl alcohol.
7. the preparation method of the crystal formation A of oxazolidinone antibacterial medicine magnesium salts according to claim 3, it is characterised in that
In described solution I, organic solvent is 0.5～3 with the volume ratio of water.
8. the preparation method of the crystal formation A of oxazolidinone antibacterial medicine magnesium salts according to claim 3, it is characterised in that
Described inorganic magnesium salt is magnesium sulfate or magnesium chloride.
9. a kind of crystal formation A of oxazolidinone antibacterial medicine magnesium salts as claimed in claim 1 or 2 is in antibiotic medicine is prepared
Application.
10. the crystal formation A of oxazolidinone antibacterial medicine magnesium salts according to claim 9 in antibiotic medicine is prepared should
Pharmaceutically acceptable with the crystal formation A of, it is characterised in that described medicine comprising oxazolidinone antibacterial medicine magnesium salts and one or more
Inert non-toxic carrier.
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| CN107353305A (en) * | 2017-07-12 | 2017-11-17 | 浙江普洛得邦制药有限公司 | The trishydroxymethylaminomethane salt and its crystal formation A, preparation method and application of Yi Zhong oxazolidinone antibacterials |
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| CN107353305A (en) * | 2017-07-12 | 2017-11-17 | 浙江普洛得邦制药有限公司 | The trishydroxymethylaminomethane salt and its crystal formation A, preparation method and application of Yi Zhong oxazolidinone antibacterials |
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