CN106632396A - Preparation method and application of gamma-crystal form rifaximin - Google Patents
Preparation method and application of gamma-crystal form rifaximin Download PDFInfo
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- CN106632396A CN106632396A CN201710010821.7A CN201710010821A CN106632396A CN 106632396 A CN106632396 A CN 106632396A CN 201710010821 A CN201710010821 A CN 201710010821A CN 106632396 A CN106632396 A CN 106632396A
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- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D498/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D498/22—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms in which the condensed system contains four or more hetero rings
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Abstract
The invention belongs to the field of chemical medicines, in particular relates to a preparation method and application of gamma-crystal form rifaximin, and aims to solve the technical problems that a solvent is difficult to recover and dehydrate, the yield is low and the product cost is extremely high because a crystal solvent contains lots of moisture. According to the scheme for solving the technical problems, the method for preparing the gamma-crystal form rifaximin comprises the following steps: a, dissolving rifaximin in a low-level ether solvent so as to obtain a mixed solution; b, drying the mixed solution, and then filtering; c, cooling the filtered mixed solution to the temperature of -50 to -80 DEG C, maintaining the same temperature, and drying under reduced pressure until the solvent is completely volatilized, thereby obtaining the gamma-crystal form rifaximin. According to the method for preparing the gamma-crystal form rifaximin provided by the invention, the solvent is convenient to recover, the crystallization yield of the gamma-crystal form rifaximin is high, the product loss is avoided, and the yield reaches 100%.
Description
Technical field
The invention belongs to chemical medicine, and in particular to the preparation method and purposes of γ crystal formation rifaximins.
Background technology
Rifaximin is the semi-synthetic derivative of Rifamycin Sodium, is a kind of wide spectrum enteron aisle antibiotic, to most grams
Positive and gramnegative bacterium, including the infection of aerobic bacteria and anaerobic bacteria has bactericidal action, its chemistry it is entitled [2S- (2R*,
16Z, 18E, 20R*, 21R*, 22S*, 23S*, 24S*, 25R*, 26S*, 27R*, 28E)] -25- acetoxyl group -5,6,21,23-
Tetrahydroxy -27- methoxyl group -2,4,11,16,20,22,24,26- prestox -2, (carbon [1,11, the 13] triolefin of epoxy 15 is sub- for 7-
Amine) benzofuran [4,5-e] pyrido [1,2-a] benzimidazole -1,15 (2H)-diketone, its structure is as shown in Equation 1：
At present, it has been found that rifaximin crystal formation species reach kind more than ten, including：α, β, γ, η, ξ etc., but for medicine
Main still this several crystal formation of α, β, γ of crystal formation of thing treatment, wherein again most commonly seen with γ crystal formations.United States Patent (USP)
US70456202B2 discloses a kind of preparation method of γ crystal formations rifaximin：Using ethanol/water mixed solvent to rifaximin
Crude product is crystallized, and crystalline solid drying under reduced pressure under ambient temperature obtains γ crystal formation rifaximins to constant weight, and crystallization yield is
84.7%.United States Patent (USP) US9403844B2 discloses the preparation method of another kind of γ crystal formations rifaximin：It is mixed using acetic acid/water
Bonding solvent is crystallized to rifaximin crude product, and crystalline solid is dried to obtain γ crystal formation rifaximins at a temperature of 100-110 DEG C, knot
Brilliant yield is 62～65%.The above obtains γ crystal formations rifaximin and all there are some drawbacks：As recrystallisation solvent contains in a large number
Moisture so that solvent recovery, particularly solvent dehydration become difficult；And the yield of method crystallized above is not high so that produce
Product high cost.
The content of the invention
The technical problem to be solved in the present invention is that recrystallisation solvent contains large quantity of moisture so that solvent recovery dehydration is difficult, and
And yield is not high so that product cost is too high.
Invention solves the scheme of above-mentioned technical problem and is to provide a kind of preparation method of γ crystal formations rifaximin, including following
Step：
A, rifaximin is dissolved in rudimentary ether solvent, obtains mixed solution；
B, above-mentioned mixed solution is dried, is subsequently filtered；
C, the mixed solution after filtration is cooled to -50 DEG C～-80 DEG C, and keeps mutually synthermal drying under reduced pressure to wave to solvent
Distribute entirely, obtain γ crystal formation rifaximins.
Wherein, in the preparation method of above-mentioned γ crystal formations rifaximin, the rudimentary ether solvent described in step a be ether, two
Any one in isopropyl ether, methyl tertiary butyl ether(MTBE), tetrahydrofuran or glycol dimethyl ether.
Wherein, in above-mentioned preparation method, rifaximin described in step a is 1 ︰ 4 with the mass volume ratio of rudimentary ether solvent
～10.
Wherein, in above-mentioned preparation method, the drier used when being dried described in step b be anhydrous sodium sulfate, molecular sieve or
Any one in activated carbon.
Wherein, in above-mentioned preparation method, the drying described in step b is to be dried to mixed solution water content below 0.5%.
Present invention also offers the pharmaceutical composition of the γ crystal formation rifaximins prepared containing said method, and its system
Into tablet.Described pharmaceutical composition is that with γ crystal formation rifaximin active components, prepared by the conventional auxiliary material of addition other drugs
Form.The constituent of aforementioned pharmaceutical compositions is：550 milligrams of γ crystal formations rifaximin, 340 milligrams of microcrystalline cellulose, carboxylic first
4 milligrams of 42 milligrams of base sodium cellulosate, 50 milligrams of tristerin, 5 milligrams of silica gel and titanium dioxide.After said composition compressing tablet
Become tablet.
The beneficial effects of the present invention is：The invention provides a kind of new method for preparing γ crystal formation rifaximins.With
In atmosphere hygroscopicity is below 1% to γ crystal formations rifaximin prepared by this method, therefore can preserve and use the longer time,
Extend shelf life of products.In addition, the preparation method for preparing γ crystal formation rifaximins provided by the present invention, due to aqueous in solvent
Amount is low, is easy to recycling design, and the rate of recovery is high, can reuse without the need for dehydration after solvent recovery.Finally, it is provided by the present invention
The method crystallization yield for preparing γ crystal formation rifaximins is high, and without product loss, yield reaches 100%.
Description of the drawings
The X-ray diffracting spectrum of the γ crystal formation rifaximins prepared by Fig. 1 is of the invention.Using X ' Pert Pro MRD X-
X ray diffractometer x, (PANalytical, Netherland), Cu K α 1 radiate (0.154056nm), graphite monochromator, tube voltage
0 °～60 ° of the θ sweep limits of 40kV, tube current 40mA, 2,0.01 °/s of sweep speed, 0.01 ° of step-length.As seen from Figure 1, γ crystal formations
Rifaximin on the X-ray powder diffraction spectrogram represented with 2 θ, 5.04 ± 0.20 °, 7.11 ± 0.20 °, 8.41 ±
0.20 ° has characteristic diffraction peak.
Specific embodiment
The preparation method of γ crystal formation rifaximins, comprises the following steps：
A, rifaximin is dissolved in rudimentary ether solvent, obtains mixed solution；
B, above-mentioned mixed solution is dried, is subsequently filtered；
C, the mixed solution after filtration is cooled to -50 DEG C～-80 DEG C, and keeps mutually synthermal drying under reduced pressure to wave to solvent
Distribute entirely, obtain γ crystal formation rifaximins.
Wherein, in the preparation method of above-mentioned γ crystal formations rifaximin, the rudimentary ether solvent described in step a be ether, two
Any one in isopropyl ether, methyl tertiary butyl ether(MTBE), tetrahydrofuran or glycol dimethyl ether.
Wherein, in above-mentioned preparation method, rifaximin described in step a is 1 ︰ 4 with the mass volume ratio of rudimentary ether solvent
～10.
Wherein, in above-mentioned preparation method, the drier used when being dried described in step b be anhydrous sodium sulfate, molecular sieve or
Any one in activated carbon.
Wherein, in above-mentioned preparation method, the drying described in step b is to be dried to mixed solution water content below 0.5%.
The preparation of the γ crystal formation rifaximins of embodiment 1
By unformed rifaximin solid, 1 gram is added under agitation in 4 milliliters of ether, treats that solid all dissolves, by 0.5
Gram anhydrous sodium sulfate is added in solution, closed stirring 2 hours, and solution is filtered under dry nitrogen atmosphere, and filtrate is through K.F
It is 0.42% that method determines moisture, and filtrate is cooled under dry nitrogen atmosphere -50 DEG C, keeps solution temperature in -50 DEG C
Drying under reduced pressure, after solvent volatilizees completely, residue is returned under a dry nitrogen atmosphere room temperature, obtains cerise powder
1 gram of solid.
The solid has following characteristics：On the X-ray powder diffraction spectrogram represented with 2 θ, 5.04 ± 0.20 °,
7.11 ± 0.20 °, 8.41 ± 0.20 °, with characteristic diffraction peak, it was demonstrated that for γ crystal formation rifaximins.
The preparation of the γ crystal formation rifaximins of embodiment 2
By unformed rifaximin solid, 1 gram is added under agitation in 7 milliliters of ether, treats that solid all dissolves, by 1 gram
Anhydrous sodium sulfate is added in solution, closed stirring 2 hours, and solution is filtered under dry nitrogen atmosphere, and filtrate is through K.F methods
It is 0.44% to determine moisture, and filtrate is cooled under dry nitrogen atmosphere -50 DEG C, keeps solution temperature to subtract in -50 DEG C
Press dry dry, after solvent volatilizees completely, residue is returned under a dry nitrogen atmosphere room temperature, obtain cerise powder and consolidate
1 gram of body.
The solid has following characteristics：On the X-ray powder diffraction spectrogram represented with 2 θ, 5.04 ± 0.20 °,
7.11 ± 0.20 °, 8.41 ± 0.20 °, with characteristic diffraction peak, it was demonstrated that for γ crystal formation rifaximins.
The preparation of the γ crystal formation rifaximins of embodiment 3
By unformed rifaximin solid, 1 gram is added under agitation in 10 milliliters of ether, treats that solid all dissolves, by 1
Gram anhydrous sodium sulfate is added in solution, closed stirring 2 hours, and solution is filtered under dry nitrogen atmosphere, and filtrate is through K.F
It is 0.38% that method determines moisture, and filtrate is cooled under dry nitrogen atmosphere -50 DEG C, keeps solution temperature in -50 DEG C
Drying under reduced pressure, after solvent volatilizees completely, residue is returned under a dry nitrogen atmosphere room temperature, obtains cerise powder
1 gram of solid.
The solid has following characteristics：On the X-ray powder diffraction spectrogram represented with 2 θ, 5.04 ± 0.20 °,
7.11 ± 0.20 °, 8.41 ± 0.20 °, with characteristic diffraction peak, it was demonstrated that for γ crystal formation rifaximins.
The preparation of the γ crystal formation rifaximins of embodiment 4
By unformed rifaximin solid, 1 gram is added under agitation in 4 milliliters of diisopropyl ethers, treats that solid all dissolves,
0.5 gram of anhydrous sodium sulfate is added in solution, closed stirring 2 hours, solution is filtered under dry nitrogen atmosphere, filtrate Jing
It is 0.47% to cross K.F methods and determine moisture, and filtrate is cooled under dry nitrogen atmosphere -50 DEG C, keep solution temperature in -
50 DEG C of drying under reduced pressure, after solvent volatilizees completely, residue are returned under a dry nitrogen atmosphere room temperature, obtain scarlet toner
1 gram of last shape solid.
The solid has following characteristics：On the X-ray powder diffraction spectrogram represented with 2 θ, 5.04 ± 0.20 °,
7.11 ± 0.20 °, 8.41 ± 0.20 °, with characteristic diffraction peak, it was demonstrated that for γ crystal formation rifaximins.
The preparation of the γ crystal formation rifaximins of embodiment 5
By unformed rifaximin solid, 1 gram is added under agitation in 4 milliliters of methyl tertiary butyl ether(MTBE)s, treats that solid is all molten
Solution, 0.5 gram of anhydrous sodium sulfate is added in solution, closed stirring 2 hours, and solution is filtered under dry nitrogen atmosphere, filter
It is 0.33% that liquid determines moisture through K.F methods, and filtrate is cooled under dry nitrogen atmosphere -50 DEG C, keeps solution temperature
Spend in -50 DEG C of drying under reduced pressure, after solvent volatilizees completely, residue is returned under a dry nitrogen atmosphere room temperature, obtain fresh
1 gram of red powder solid.
The solid has following characteristics：On the X-ray powder diffraction spectrogram represented with 2 θ, 5.04 ± 0.20 °,
7.11 ± 0.20 °, 8.41 ± 0.20 °, with characteristic diffraction peak, it was demonstrated that for γ crystal formation rifaximins.
The preparation of the γ crystal formation rifaximins of embodiment 6
By unformed rifaximin solid, 1 gram is added under agitation in 4 milliliters of tetrahydrofurans, treats that solid all dissolves,
0.5 gram of anhydrous sodium sulfate is added in solution, closed stirring 2 hours, solution is filtered under dry nitrogen atmosphere, filtrate Jing
It is 0.43% to cross K.F methods and determine moisture, and filtrate is cooled under dry nitrogen atmosphere -50 DEG C, keep solution temperature in -
50 DEG C of drying under reduced pressure, after solvent volatilizees completely, residue are returned under a dry nitrogen atmosphere room temperature, obtain scarlet toner
1 gram of last shape solid.
The solid has following characteristics：On the X-ray powder diffraction spectrogram represented with 2 θ, 5.04 ± 0.20 °,
7.11 ± 0.20 °, 8.41 ± 0.20 °, with characteristic diffraction peak, it was demonstrated that for γ crystal formation rifaximins.
The preparation of the γ crystal formation rifaximins of embodiment 7
By unformed rifaximin solid, 1 gram is added under agitation in 4 milliliters of glycol dimethyl ethers, treats that solid is all molten
Solution, 0.5 gram of anhydrous sodium sulfate is added in solution, closed stirring 2 hours, and solution is filtered under dry nitrogen atmosphere, filter
It is 0.27% that liquid determines moisture through K.F methods, and filtrate is cooled under dry nitrogen atmosphere -50 DEG C, keeps solution temperature
Spend in -50 DEG C of drying under reduced pressure, after solvent volatilizees completely, residue is returned under a dry nitrogen atmosphere room temperature, obtain fresh
1 gram of red powder solid.
The solid has following characteristics on the X-ray powder diffraction spectrogram represented with 2 θ, 5.04 ± 0.20 °, 7.11
± 0.20 °, 8.41 ± 0.20 °, with characteristic diffraction peak, it was demonstrated that for γ crystal formation rifaximins.
The preparation of the γ crystal formation rifaximins of embodiment 8
By unformed rifaximin solid, 1 gram is added under agitation in 4 milliliters of ether, treats that solid all dissolves, by 1 gram
Activated 3A molecular sieves are added in solution, closed stirring 2 hours, and solution is filtered under dry nitrogen atmosphere, filtrate Jing
It is 0.19% to cross K.F methods and determine moisture, and filtrate is cooled under dry nitrogen atmosphere -50 DEG C, keep solution temperature in -
50 DEG C of drying under reduced pressure, after solvent volatilizees completely, residue are returned under a dry nitrogen atmosphere room temperature, obtain scarlet toner
1 gram of last shape solid.
The solid has following characteristics：On the X-ray powder diffraction spectrogram represented with 2 θ, 5.04 ± 0.20 °,
7.11 ± 0.20 °, 8.41 ± 0.20 °, with characteristic diffraction peak, it was demonstrated that for γ crystal formation rifaximins.
The preparation of the γ crystal formation rifaximins of embodiment 9
By unformed rifaximin solid, 1 gram is added under agitation in 4 milliliters of ether, treats that solid all dissolves, by 1 gram
Activated carbon is added in solution, closed stirring 2 hours, and solution is filtered under dry nitrogen atmosphere, and filtrate determines through K.F methods
Moisture is 0.45%, and filtrate is cooled under dry nitrogen atmosphere -50 DEG C, keeps solution temperature dry in -50 DEG C of decompressions
It is dry, after solvent volatilizees completely, residue is returned under a dry nitrogen atmosphere room temperature, obtain cerise pulverulent solids 1
Gram.
The solid has following characteristics：On the X-ray powder diffraction spectrogram represented with 2 θ, 5.04 ± 0.20 °,
7.11 ± 0.20 °, 8.41 ± 0.20 °, with characteristic diffraction peak, it was demonstrated that for γ crystal formation rifaximins.
The preparation of the γ crystal formation rifaximins of embodiment 10
By unformed rifaximin solid, 1 gram is added under agitation in 4 milliliters of ether, treats that solid all dissolves, by 0.5
Gram anhydrous sodium sulfate is added in solution, closed stirring 2 hours, and solution is filtered under dry nitrogen atmosphere, and filtrate is through K.F
It is 0.42% that method determines moisture, and filtrate is cooled under dry nitrogen atmosphere -65 DEG C, keeps solution temperature in -65 DEG C
Drying under reduced pressure, after solvent volatilizees completely, residue is returned under a dry nitrogen atmosphere room temperature, obtains cerise powder
1 gram of solid.
The solid has following characteristics：On the X-ray powder diffraction spectrogram represented with 2 θ, 5.04 ± 0.20 °,
7.11 ± 0.20 °, 8.41 ± 0.20 °, with characteristic diffraction peak, it was demonstrated that for γ crystal formation rifaximins.
The preparation of the γ crystal formation rifaximins of embodiment 11
By unformed rifaximin solid, 1 gram is added under agitation in 4 milliliters of ether, treats that solid all dissolves, by 0.5
Gram anhydrous sodium sulfate is added in solution, closed stirring 2 hours, and solution is filtered under dry nitrogen atmosphere, and filtrate is through K.F
It is 0.44% that method determines moisture, and filtrate is cooled under dry nitrogen atmosphere -80 DEG C, keeps solution temperature in -80 DEG C
Drying under reduced pressure, after solvent volatilizees completely, residue is returned under a dry nitrogen atmosphere room temperature, obtains cerise powder
1 gram of solid.
The solid has following characteristics：On the X-ray powder diffraction spectrogram represented with 2 θ, 5.04 ± 0.20 °,
7.11 ± 0.20 °, 8.41 ± 0.20 °, with characteristic diffraction peak, it was demonstrated that for γ crystal formation rifaximins.
The preparation of the γ crystal formation rifaximins of embodiment 12
By alpha-crystal form rifaximin solid, 1 gram is added under agitation in 4 milliliters of ether, treats that solid all dissolves, by 1 gram
Anhydrous sodium sulfate is added in solution, closed stirring 2 hours, and solution is filtered under dry nitrogen atmosphere, and filtrate is through K.F methods
It is 0.37% to determine moisture, and filtrate is cooled under dry nitrogen atmosphere -80 DEG C, keeps solution temperature to subtract in -80 DEG C
Press dry dry, after solvent volatilizees completely, residue is returned under a dry nitrogen atmosphere room temperature, obtain cerise powder and consolidate
1 gram of body.
The solid has following characteristics：On the X-ray powder diffraction spectrogram represented with 2 θ, 5.04 ± 0.20 °,
7.11 ± 0.20 °, 8.41 ± 0.20 °, with characteristic diffraction peak, it was demonstrated that for γ crystal formation rifaximins.
The preparation of the γ crystal formation rifaximins of embodiment 13
By beta crystal rifaximin solid, 1 gram is added under agitation in 4 milliliters of ether, treats that solid all dissolves, by 1 gram
Anhydrous sodium sulfate is added in solution, closed stirring 2 hours, and solution is filtered under dry nitrogen atmosphere, and filtrate is through K.F methods
It is 0.48% to determine moisture, and filtrate is cooled under dry nitrogen atmosphere -80 DEG C, keeps solution temperature to subtract in -80 DEG C
Press dry dry, after solvent volatilizees completely, residue is returned under a dry nitrogen atmosphere room temperature, obtain cerise powder and consolidate
1 gram of body.
The solid has following characteristics：On the X-ray powder diffraction spectrogram represented with 2 θ, 5.04 ± 0.20 °,
7.11 ± 0.20 °, 8.41 ± 0.20 °, with characteristic diffraction peak, it was demonstrated that for γ crystal formation rifaximins.
The preparation of the γ crystal formation rifaximins of embodiment 14
By ξ crystal formation rifaximins solid, 1 gram is added under agitation in 4 milliliters of ether, treats that solid all dissolves, by 0.5
Gram anhydrous sodium sulfate is added in solution, closed stirring 2 hours, and solution is filtered under dry nitrogen atmosphere, and filtrate is through K.F
It is 0.41% that method determines moisture, and filtrate is cooled under dry nitrogen atmosphere -80 DEG C, keeps solution temperature in -80 DEG C
Drying under reduced pressure, after solvent volatilizees completely, residue is returned under a dry nitrogen atmosphere room temperature, obtains cerise powder
1 gram of solid.
The solid has following characteristics：On the X-ray powder diffraction spectrogram represented with 2 θ, 5.04 ± 0.20 °,
7.11 ± 0.20 °, 8.41 ± 0.20 °, with characteristic diffraction peak, it was demonstrated that for γ crystal formation rifaximins.
The γ crystal formation rifaximins X-ray diffraction of embodiment 15 is tested
Using X ' Pert Pro MRD x-ray diffractometers, (PANalytical, Netherland), Cu K α 1 are radiated
(0.154056nm), graphite monochromator, tube voltage 40kV, tube current 40mA, 20 ° of θ sweep limits～60 °, sweep speed
0.01 °/s, 0.01 ° of step-length.X-ray diffracting spectrum (the accompanying drawing of γ crystal formation rifaximins is obtained：Fig. 1), the γ crystal formations profit good fortune
Former times is bright on the X-ray powder diffraction spectrogram represented with 2 θ, in 5.04 ± 0.20 °, 7.11 ± 0.20 °, 8.41 ± 0.20 °, tool
There is characteristic diffraction peak.
The γ crystal formation rifaximins hygroscopicity of embodiment 16 is investigated
It is dry in 105 DEG C during γ crystal formations rifaximin prepared by above example is weighed respectively into about 0.5 gram as measuring cup
Dry 6 hours, subsequently as room temperature is cooled in drier, after precise weighing, it is placed in the humidistat that humidity is 90% and balances 10
My god, weigh, according to formula：Weight Х 100%=hydroscopicities calculate hydroscopicity before (weight before weight-balance after balance)/balance,
Measurement result is shown in Table 1.
The γ crystal formation rifaximin hygroscopicity data of table 1
Can be seen that from above-mentioned experimental result：The hygroscopicity of the γ crystal formation rifaximins that the present invention is provided is significantly lower than 1%.
Pharmaceutical composition of the embodiment 17 containing γ crystal formation rifaximins
The invention provides purposes of the γ crystal formations rifaximin in rifaximin tablet is prepared, the pharmaceutical composition be with
γ crystal formation rifaximin active components, the conventional auxiliary material of addition other drugs is prepared from.The constituent of aforementioned pharmaceutical compositions
For：550 milligrams of γ crystal formations rifaximin, 340 milligrams of microcrystalline cellulose, 42 milligrams of sodium carboxymethylcellulose, tristerin
4 milligrams of 50 milligrams, 5 milligrams of silica gel and titanium dioxide, by compressing tablet, becoming contain γ crystal formations profit good fortune former times per piece for combination of the above thing
Bright 550 milligrams of tablet.
Claims (8)
1. the preparation method of γ crystal formations rifaximin, comprises the following steps：
A, rifaximin is dissolved in rudimentary ether solvent, obtains mixed solution；
B, above-mentioned mixed solution is dried, is subsequently filtered；
C, the mixed solution after filtration is cooled to -50 DEG C～-80 DEG C, and keeps mutually synthermal drying under reduced pressure to be evaporated completely to solvent
Entirely, γ crystal formation rifaximins are obtained.
2. the preparation method of γ crystal formations rifaximin according to claim 1, it is characterised in that：It is rudimentary described in step a
Ether solvent is any one in ether, diisopropyl ether, methyl tertiary butyl ether(MTBE), tetrahydrofuran or glycol dimethyl ether.
3. the preparation method of γ crystal formations rifaximin according to claim 1, it is characterised in that：Sharp good fortune former times described in step a
The bright mass volume ratio with rudimentary ether solvent is 1 ︰ 4～10.
4. the preparation method of γ crystal formations rifaximin according to claim 1, it is characterised in that：When being dried described in step b
The drier for using is any one in anhydrous sodium sulfate, molecular sieve or activated carbon.
5. the preparation method of γ crystal formations rifaximin according to claim 1, it is characterised in that：Drying described in step b
To be dried to mixed solution water content below 0.5%.
6. the γ crystal formation rifaximins that the γ crystal formation rifaximin preparation methods described in any one of Claims 1 to 5 are prepared
Pharmaceutical composition, and its made by tablet.
7. pharmaceutical composition according to claim 6, it is characterised in that：Described pharmaceutical composition is with γ crystal formations profit good fortune
Former times bright active component, the conventional auxiliary material of addition other drugs is prepared from；The constituent of aforementioned pharmaceutical compositions is：γ crystal formations profit
Good fortune former times is bright 550 milligrams, 340 milligrams of microcrystalline cellulose, 42 milligrams of sodium carboxymethylcellulose, 50 milligrams of tristerin, silica gel 5
4 milligrams of milligram and titanium dioxide.
8. pharmaceutical composition according to claim 6, it is characterised in that：Tablet will be made after described composition compressing tablet.
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| CN106632396B (en) | 2019-01-11 |
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