CN101475497B - Method for preparing terbutaline sulphate crystal form B meeting medicinal requirements - Google Patents
Method for preparing terbutaline sulphate crystal form B meeting medicinal requirements Download PDFInfo
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- CN101475497B CN101475497B CN2008101898577A CN200810189857A CN101475497B CN 101475497 B CN101475497 B CN 101475497B CN 2008101898577 A CN2008101898577 A CN 2008101898577A CN 200810189857 A CN200810189857 A CN 200810189857A CN 101475497 B CN101475497 B CN 101475497B
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Abstract
The invention provides a method for preparing terbutaline sulphate B crystal form. The method comprises: selecting a solvent, dissolving 1-(3,5-dibenzyloxy phenyl)-2-n-tert-butyl aminoethanol into the solvent, removing benzyl groups through hydrogenolysis by a general method, obtaining terbutaline free alkali, and adding sulfuric acid into the terbutaline free alkali to form terbutaline sulphate of crystal form B; or dissolving terbutaline sulphate of non-crystal form B into the solvent, stirring the terbutaline sulphate of the non-crystal form B in the solvent at a certain temperature until the terbutaline sulphate of the non-crystal form B is converted into the terbutaline sulphate B crystal form through dissolution and lixiviation, and reclaiming the leached terbutaline sulphate B crystal form. The method has the advantage of obtaining the terbutaline sulphate B crystal form which has stable chemical and physical properties and meets the requirements of medical preparation.
Description
Technical field
The invention belongs to medical technical field, be specifically related to α-[(uncle's fourth is amino) methyl]-3,5-dihydroxybenzyl alcohol vitriol (2: 1) is the preparation method of terbutaline sulphate crystal B.
Background technology
α-[(uncle's fourth is amino) methyl]-3,5-dihydroxybenzyl alcohol vitriol (2: 1) (this paper bricalin) is 23031-32-5 CAS number, molecular formula is (C
12H
19NO
3)
2H
2SO
4And have a following structure:
The alternative excited beta 2-adrenergic receptor of bricalin, lax bronchial smooth muscle, the oedema that suppresses the release of endogenous spasmogen and can suppress to cause by endogenous messenger and mucociliary clearance aggravation.Its bronchiectatic activity is close with husky fourth ammonia alcohol.The antiasthmatic effect of these article 2.5mg is suitable with the 25mg ephedrine.Animal or human's isolated experiment confirms that its effect to the heart β1Shou Ti is minimum, and its excitation to heart only reaches 1/100 of Racemic isoproterenol.The treatment of the bronchospasm when bricalin is mainly used in bronchial asthma, asthmatic bronchitis and chronic obstructive lung illness clinically.Quiet then can be suppressed the uterine contraction that spontaneous uterine contraction and pitocin cause, prevent premature etc. continuously.
Patent US3937838 has early disclosed structure, preparation technology and it of the compound bricalin clinical application as selectivity beta 2-adrenergic receptor agonist.Document (Chinese Journal of Pharmaceuticals; 1999/30) disclosed a kind ofly, be used for synthetic (aforesaid method forms the terbutaline sulphate crystal B that solvent that vitriol or treating process adopt can not obtain meeting medicinal requirements at terbutaline) of bricalin than simple synthesis method.This medicine is in clinical application, and main administering mode has: atomizing sucks, oral, injection.Research (Jaeschke R, Guyall GH, Willan A; Et al.The effect of increasing doses of betaagonists on spirometry; Exercise capacity, and quality of life in patients with chronic airflow limitation.Thorax, 1994; 49:478.) showing that the atomizing inhalation is the best administering mode of beta receptor agonist, this administering mode has less heart, blood vessel spinoff.Bricalin is a suspension aerosol, and this formulation at first will be carried out the micronization processes of medicine in the preparation process.For polymorph medicine, this process usually can cause the variation of crystal formation.Crystal formation is the critical nature of compound, and to the stability of medicine and product quality homogeneity, bioavailability, preparation etc. are all influential.In addition, from the dissection and the physiological structure analysis of segmental bronchus, bronchiole and lung, for medicine effectively being distributed or being deposited on above-mentioned therapentic part, the granularity that requires medicine or pastille droplet is about 5um.Excessive (greater than 10um) or too small (less than 1um) thus granularity drug deposition is lessened the curative effect at therapentic part.Research shows that the physical properties of main ingredient can exert an influence to the size of drug particle size.Further, owing to differences of physical properties between each crystal formation of polymorph medicine also will impact the preparation process.Document (CRYSTAL GROWNTH&DESIGN, 2008.Vol8.NO1 80-90) discloses bricalin and can exist with five kinds of crystal formations at least, is respectively: crystal form A, crystal form B, monohydrate, polyhydrate, acetate compound.Document author also reaches a conclusion through experiment (Solubility experiments in water-ethanol mixtures): compare with other crystal formations of bricalin, terbutaline sulphate crystal B is to stablize crystal formation.Further specify, terbutaline sulphate crystal B is more suitable in the preparation of suspension aerosol and other formulations.Although relevant for the report of terbutaline sulphate crystal B, do not see the method for preparing terbutaline sulphate crystal B that clearly discloses up to now as yet.
In sum, need in this area a kind of easy, stable, prepare the method for the terbutaline sulphate crystal B that meets medicinal requirements efficiently.
Summary of the invention
The present invention relates to terbutaline sulphate crystal B and preparation method; This crystal formation is characterised in that the radiation with Co-K α; Be positioned at about 9.9,12.9,21.5,22.7,25.0,27.6,28.9 ± 0.2 degree 2 θ powder X-ray RD peaks, can further characterize with powder X-ray RD pattern that is positioned at about 8.5,11.3,14.9,15.8,20.0,23.6 ± 0.2 degree, 2 θ or powder X-ray RD pattern as shown in Figure 1 basically.
Present method is to select a kind of solvent, and 1-(3,5 two benzyloxy phenyl)-2-tertiary butyl amido ethanol is dissolved in wherein; Slough benzyl through the universal method hydrogenolysis; Get the terbutaline free alkali, add the bricalin that sulfuric acid forms crystal form B again, reclaim the terbutaline sulphate crystal B that forms then;
Or; Select a kind of solvent; Bricalin in this solvent has low solubility, the bricalin of armorphous B is dissolved in wherein, at 0 ℃ to the reflux temperature bricalin suspension 10 minutes-100 hours of this solvent of stirring down; Terbutaline sulphate crystal B will form, and reclaims the terbutaline sulphate crystal B that forms then.
Said solvent is the solvent orange 2 A that water and esters solvent form, and its proportion of composing is represented with the water cut of this esters solvent, is about 0.03% to saturated, and the solvent orange 2 A consumption under agitation forms suspension for guaranteeing bricalin at least;
Said esters solvent is selected from ETHYLE ACETATE, propyl acetate, butylacetate, isopropyl acetate, ethyl propionate, propyl propionate, butyl propionate, isopropyl propionate, oil of Niobe, ethyl benzoate or methyl aceto acetate or other can be used as the ester class with following structure that solvent uses:
R wherein
2Expression straight or branched alkane; R
1Expression straight or branched alkane, or contain heteroatoms or the substituted alkane derivatives of heteroatoms, or C
6-C
12Aryl, wherein the hydrogen on the aryl can be replaced by other substituting groups.
Preferably, said solvent orange 2 A is the mixed solvent of water and ETHYLE ACETATE, and its ratio is expressed as 0.03% to saturated with the ETHYLE ACETATE water cut.
Preferably; 1-(3; 5 two benzyloxy phenyl)-bricalin of 2-tertiary butyl amido ethanol or armorphous B and total solvent amount optimum proportion be by the bricalin 10ml of every gram 1-(3,5 two benzyloxy phenyl)-2-tertiary butyl amido ethanol or the armorphous B amount use solvent to 20ml.
Described TR is 0 ℃ and arrives reflux temperature that optimum temperature range is 18 ℃ to 40 ℃; Churning time is 10 minutes-100 hours, best churning time 24-36 hour.
Preferably, the method for reclaim(ed) sulfuric acid terbutaline crystal form B is for to wave solvent or dried recovered terbutaline sulphate crystal B under 50 ℃ of nitrogen gas stream under normal pressure.
Same principle, the solvent orange 2 A of aforesaid method can be used as terbutaline and become the solvent in the vitriol process, also can be used as the solvent of POV terbutaline crystal form B.
In present method, the multiple mixed solvent that solvent can adopt solvent orange 2 A and solvent B to form.Said solvent B is selected from the organic solvent alkanes, ester or oils, aromatic hydrocarbons, ethers, alcohols, halogenated hydrocarbon and DMF, DMSO or other organic solvents; The ratio of solvent orange 2 A and solvent B is 10: 0～1: 9, and optimum proportion is 10: 0～7: 3; The ratio of the bricalin of mixed solvent consumption and 1-(3,5 two benzyloxy phenyl)-2-tertiary butyl amido ethanol or armorphous B is 1ml～1000ml: 1g.
Organic solvent B is made up of with arbitrary proportion one or more solvents, and wherein alkanes is selected from hexane, heptane, hexanaphthene, and sherwood oil or other can be used as the alkane that solvent uses; The ester class is selected from ETHYLE ACETATE, propyl acetate, butylacetate, isopropyl acetate, oil of Niobe or ethyl benzoate or other can be used as ester or the grease that solvent uses; Ketone is selected from acetone, 2-butanone or pimelinketone or other can be used as the ketone that solvent uses; Aromatic hydrocarbons is selected from benzene, toluene or YLENE or other can be used as the aromatic hydrocarbons that solvent uses; Ethers is selected from THF, ether, isopropyl ether or MTBE or other and can be used as the ether that solvent uses, and alcohols is selected from methyl alcohol, ethanol Virahol, various butanols, various amylalcohol, various hexanol or other can be used as the alcohol that solvent uses; Halogenated hydrocarbon is selected from methylene dichloride, chloroform or other can be used as the halocarbon that solvent uses.
Preferably, solvent B is one or more in acetone, benzene, THF, ether, ethanol, methylene dichloride, the chloroform.
Preferably, mixed solvent consists of water, ETHYLE ACETATE, solvent B (as above-mentioned, comprising acetone, benzene, THF, ether, ethanol, methylene dichloride, chloroform).
Preferably, the composition of solvent B in mixed solvent is less than 10%.
Preferably, the ratio 10ml of the bricalin of mixed solvent consumption and 1-(3,5 two benzyloxy phenyl)-2-tertiary butyl amido ethanol or armorphous B uses solvent to the amount of 20ml.
Described TR is 0 ℃ and arrives reflux temperature that optimum temperature range is 18 ℃ to 40 ℃; Churning time is 10 minutes-100 hours, best churning time 24-36 hour.
Preferably, the method for reclaim(ed) sulfuric acid terbutaline crystal form B is for to wave solvent or dried recovered terbutaline sulphate crystal B under 50 ℃ of nitrogen gas stream under normal pressure.
Same principle, the solvent of aforesaid method can be used as terbutaline and become the solvent in the vitriol process, also can be used as the solvent of POV terbutaline crystal form B.
Advantage of the present invention is: through simple aforesaid method, it is stable to obtain chemistry and physical properties, the terbutaline sulphate crystal B that the fulfilling medicinal preparation requires.
Description of drawings
Fig. 1 illustrates the XRD diffractogram of terbutaline sulphate crystal B
Embodiment
Through the following example with reference to detailed description preparation method of the present invention, further explain the present invention.It is obvious that to one of ordinary skill in the art, without departing from the scope of the invention, can implement the many improvement to material and method.
Embodiment 1
0.5g non-B crystal formation bricalin stirred 24 hours down in 25 ℃ in the aqueous ETHYLE ACETATE of 10ml (water saturation), then the gained suspension was dried to constant weight 50 ℃ of nitrogen gas stream.Get terbutaline sulphate crystal B.
Embodiment 2
0.5g non-B crystal formation bricalin stirred 24 hours down in 25 ℃ in the aqueous ETHYLE ACETATE of 10ml (water semi-saturation), then the gained suspension was dried to constant weight under 50 ℃ of nitrogen gas stream.Get terbutaline sulphate crystal B.
Embodiment 3
0.5g non-B crystal formation bricalin stirred 24 hours down in 35 ℃ in the aqueous ETHYLE ACETATE of 10ml (water saturation), then the gained suspension was dried to constant weight under 50 ℃ of nitrogen gas stream.Get terbutaline sulphate crystal B.
Embodiment 4
0.5g non-B crystal formation bricalin stirred 36 hours down in 25 ℃ in the aqueous ETHYLE ACETATE of 10ml (water saturation), then the gained suspension was dried to constant weight under 50 ℃ of nitrogen gas stream.Get terbutaline sulphate crystal B.
Embodiment 5
0.5g non-B crystal formation bricalin stirred 24 hours down in 25 ℃ in the mixed solvent that aqueous ETHYLE ACETATE (water saturation) 9ml, acetone 1ml form, and then the gained suspension was dried to constant weight under 50 ℃ of nitrogen gas stream.Get terbutaline sulphate crystal B.
Embodiment 6
0.5g non-B crystal formation bricalin stirred 24 hours down in 25 ℃ in the mixed solvent that aqueous ETHYLE ACETATE (water saturation) 9ml, benzene 1ml form, and then the gained suspension was dried to constant weight under 50 ℃ of nitrogen gas stream.Get terbutaline sulphate crystal B.
Embodiment 7
0.5g non-B crystal formation bricalin stirred 24 hours down in 25 ℃ in the mixed solvent that aqueous ETHYLE ACETATE (water saturation) 9ml, THF 1ml form, and then the gained suspension was dried to constant weight under 50 ℃ of nitrogen gas stream.Get terbutaline sulphate crystal B.
Embodiment 8
0.5g non-B crystal formation bricalin stirred 24 hours down in 25 ℃ in the mixed solvent that aqueous ETHYLE ACETATE (water saturation) 9ml, ether 1ml form, and then the gained suspension was dried to constant weight under 50 ℃ of nitrogen gas stream.Get terbutaline sulphate crystal B.
Embodiment 9
0.5g non-B crystal formation bricalin stirred 24 hours down in 25 ℃ in the mixed solvent that aqueous ETHYLE ACETATE (water saturation) 9ml, ethanol 1ml form, and then the gained suspension was dried to constant weight under 50 ℃ of nitrogen gas stream.Get terbutaline sulphate crystal B.
0.5g non-B crystal formation bricalin stirred 24 hours down in 25 ℃ in the mixed solvent that aqueous ETHYLE ACETATE (water saturation) 9ml, methylene dichloride 1ml form, and then the gained suspension was dried to constant weight under 50 ℃ of nitrogen gas stream.Get terbutaline sulphate crystal B.
Embodiment 11
0.5g non-B crystal formation bricalin stirred 24 hours down in 25 ℃ in the mixed solvent that aqueous ETHYLE ACETATE (water saturation) 9ml, chloroform 1ml form, and then the gained suspension was dried to constant weight under 50 ℃ of nitrogen gas stream.Get terbutaline sulphate crystal B.
0.5g non-B crystal formation bricalin stirred 24 hours down in 25 ℃ in the aqueous ETHYLE ACETATE of 10ml (water saturation); Filter, in 50 ℃ of decompressions (but also normal pressure) drying 1 hour, again 80 ℃ of dryings 1 hour; Be dried to constant weight at 120 ℃ at last, get terbutaline sulphate crystal B.
Embodiment 13
0.5g non-B crystal formation bricalin stirred 24 hours down in 25 ℃ in the aqueous ETHYLE ACETATE of 5ml (water saturation); Filter, in 50 ℃ of decompressions (but also normal pressure) drying 1 hour, again 80 ℃ of dryings 1 hour; Be dried to constant weight at 120 ℃ at last, get terbutaline sulphate crystal B.
0.5g non-B crystal formation bricalin stirred 24 hours down in 35 ℃ in the aqueous ETHYLE ACETATE of 10ml (water saturation); Filter, in 50 ℃ of decompressions (but also normal pressure) drying 1 hour, again 80 ℃ of dryings 1 hour; Be dried to constant weight at 120 ℃ at last, get terbutaline sulphate crystal B.
Embodiment 15
0.5g non-B crystal formation bricalin stirred 36 hours down in 25 ℃ in the aqueous ETHYLE ACETATE of 10ml (water saturation); Filter, in 50 ℃ of decompressions (but also normal pressure) drying 1 hour, again 80 ℃ of dryings 1 hour; Be dried to constant weight at 120 ℃ at last, get terbutaline sulphate crystal B.
0.5g non-B crystal formation bricalin stirred 24 hours down in 25 ℃ in the mixed solvent that aqueous ETHYLE ACETATE (water saturation) 9ml, acetone 1ml form; Filter; In dry 1 hour of 50 ℃ of decompressions (but also normal pressure); 80 ℃ of dryings 1 hour, be dried to constant weight at 120 ℃ at last again, terbutaline sulphate crystal B.
Embodiment 17
0.5g non-B crystal formation bricalin stirred 24 hours down in 25 ℃ in the mixed solvent that aqueous ETHYLE ACETATE (water saturation) 9ml, benzene 1ml form; Filter; In dry 1 hour of 50 ℃ of decompressions (but also normal pressure); 80 ℃ of dryings 1 hour, be dried to constant weight at 120 ℃ at last again, terbutaline sulphate crystal B.
0.5g non-B crystal formation bricalin stirred 24 hours down in 25 ℃ in the mixed solvent that aqueous ETHYLE ACETATE (water saturation) 9ml, THF 1ml form; Filter; In dry 1 hour of 50 ℃ of decompressions (but also normal pressure); 80 ℃ of dryings 1 hour, be dried to constant weight at 120 ℃ at last again, terbutaline sulphate crystal B.
Embodiment 19
0.5g non-B crystal formation bricalin stirred 24 hours down in 25 ℃ in the mixed solvent that aqueous ETHYLE ACETATE (water saturation) 9ml, ether 1ml form; Filter; In dry 1 hour of 50 ℃ of decompressions (but also normal pressure); 80 ℃ of dryings 1 hour, be dried to constant weight at 120 ℃ at last again, terbutaline sulphate crystal B.
0.5g non-B crystal formation bricalin stirred 24 hours down in 25 ℃ in the mixed solvent that aqueous ETHYLE ACETATE (water saturation) 9ml, ethanol 1ml form; Filter; In dry 1 hour of 50 ℃ of decompressions (but also normal pressure); 80 ℃ of dryings 1 hour, be dried to constant weight at 120 ℃ at last again, terbutaline sulphate crystal B.
Embodiment 21
0.5g non-B crystal formation bricalin stirred 24 hours down in 25 ℃ in the mixed solvent that aqueous ETHYLE ACETATE (water saturation) 9ml, methylene dichloride 1ml form; Filter; In dry 1 hour of 50 ℃ of decompressions (but also normal pressure); 80 ℃ of dryings 1 hour, be dried to constant weight at 120 ℃ at last again, terbutaline sulphate crystal B.
0.5g non-B crystal formation bricalin stirred 24 hours down in 25 ℃ in the mixed solvent that aqueous ETHYLE ACETATE (water saturation) 9ml, chloroform 1ml form; Filter; In dry 1 hour of 50 ℃ of decompressions (but also normal pressure); 80 ℃ of dryings 1 hour, be dried to constant weight at 120 ℃ at last again, terbutaline sulphate crystal B.
Embodiment 23
It is in 1.7% the ETHYLE ACETATE that 1-(3,5 two benzyloxy phenyl)-2-tertiary butyl amido ethanol 18g is joined the 200ml water cut, by universal method; Add 10%Pd-C 1.8g, feed hydrogen, reaction 2h in 40-50 ℃ of normal pressure; Filter; Filtrating adds 2.4N sulfuric acid 4.7ml under the ice bath cooling, more than the crystallisation by cooling 2h, get the solid 10g of white terbutaline sulphate crystal B.
1-(3,5 two benzyloxy phenyl)-2-tertiary butyl amido ethanol 180g is joined in the mixed solvent of aqueous ETHYLE ACETATE of 1800ml (water saturation) and THF 200ml composition, by universal method; Add 10%Pd-C 18g, feed hydrogen, reaction 2h in 40-50 ℃ of normal pressure; Filter; Filtrating adds 2.4N sulfuric acid 47ml under the ice bath cooling, more than the crystallisation by cooling 2h, get the solid 108g of white terbutaline sulphate crystal B.
Embodiment 25
0.5g non-B crystal formation bricalin stirred 24 hours down in 25 ℃ in the aqueous methyl aceto acetate of 10ml (water saturation); Filter; With a small amount of ether washing leaching cake, collect filter cake in 50 ℃ of decompressions (but also normal pressure) drying 1 hour, again 80 ℃ of dryings 1 hour; Be dried to constant weight at 120 ℃ at last, get terbutaline sulphate crystal B.
Get 1-(3,5-two Bian oxygen base phenyl)-2-n-butylamine-based ethanol 1g, ETHYLE ACETATE (water saturation) 10ml, Pd-C0.1g and add in the reactor drum, in 50 ℃ of following hydrogenolysis of normal pressure three hours.Stop heating, remove by filter Pd-C.In the filtrating that collection obtains, add an amount of 50% sulfuric acid, left standstill three hours, get the terbutaline sulphate crystal B bullion.The terbutaline sulphate crystal B bullion that again collection is obtained stirred 12 hours in water saturated ETHYLE ACETATE, got the terbutaline sulphate crystal B elaboration.
Obviously the disclosed the present invention of this paper is through taking into full account to realize above-mentioned target; But should be appreciated that one of ordinary skill in the art can propose many improvement and embodiment; Therefore, accompanying claims covers all these and falls into the improvement and the embodiment of purport of the present invention and scope.
Claims (6)
1. be used to prepare the method for terbutaline sulphate crystal B; Wherein terbutaline sulphate crystal B is characterised in that: use Co-K α radiation; 9.9,12.9,21.5,22.7,25.0,27.6,28.9 ± 0.2 the peak is arranged to spend the X-ray powder diffraction spectrum that 2 θ represent; Can further characterize with powder X-ray RD pattern that is positioned at about 8.5,11.3,14.9,15.8,20.0,23.6 ± 0.2 degree, 2 θ or powder X-ray RD pattern as shown in Figure 1, this method steps is following:
Select a kind of solvent, the bricalin in this solvent has low solubility, and the bricalin of armorphous B is dissolved in wherein, stirs, and terbutaline sulphate crystal B will form, and reclaims the terbutaline sulphate crystal B that forms then;
Said solvent is the solvent orange 2 A that water and esters solvent form, and its proportion of composing is represented with the water cut of this esters solvent, is about 0.03% to saturated, and the solvent orange 2 A consumption under agitation forms suspension for guaranteeing bricalin at least;
Said esters solvent is selected from ETHYLE ACETATE, propyl acetate, butylacetate, isopropyl acetate, ethyl propionate, propyl propionate, butyl propionate, isopropyl propionate, oil of Niobe, ethyl benzoate, methyl aceto acetate or other can be used as the ester class with following structure that solvent uses:
R wherein
2Expression straight or branched alkane; R
1Expression straight or branched alkane, or contain heteroatoms or the substituted alkane derivatives of heteroatoms, or C
6-C
12Aryl, wherein the hydrogen on the aryl can be replaced by other substituting groups.
2. the preparation method of terbutaline sulphate crystal B according to claim 1, it is characterized in that: the ratio of the bricalin of said solvent orange 2 A consumption and armorphous B is 1ml～1000ml: 1g.
3. the preparation method of terbutaline sulphate crystal B according to claim 2, it is characterized in that: the ratio of the bricalin of said solvent orange 2 A consumption and armorphous B is 10ml～20ml: 1g.
4. according to the preparation method of one of claim 1-3 described terbutaline sulphate crystal B, it is characterized in that: said solvent orange 2 A is the mixed solvent of water and ETHYLE ACETATE, and the ratio of water and ETHYLE ACETATE is expressed as 0.03% to saturated with the ETHYLE ACETATE water cut.
5. method according to claim 1 is characterized in that: the TR of said stirring is 0 ℃ and arrives reflux temperature; Churning time is 10 minutes-100 hours.
6. method according to claim 1 is characterized in that terbutaline sulphate crystal B that said recovery forms adopts a kind of in following three kinds of methods:
A. remove by filter solvent, solid is through decompression or normal pressure heat drying, to obtain terbutaline sulphate crystal B then;
B. under reduced pressure remove and desolvate, solid is through decompression or normal pressure heat drying, to obtain terbutaline sulphate crystal B then;
C. under nitrogen gas stream effect and heating, fling to solvent, solid is through decompression or normal pressure heat drying, to obtain terbutaline sulphate crystal B then.
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| CNA2008102329906A CN101391965A (en) | 2008-11-02 | 2008-11-02 | Method for preparing terbutaline sulphate crystal B fulfilling medicinal requirements |
| CN200810232990.6 | 2008-11-02 | ||
| CN2008101898577A CN101475497B (en) | 2008-11-02 | 2008-12-27 | Method for preparing terbutaline sulphate crystal form B meeting medicinal requirements |
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| CN103664654A (en) * | 2013-11-12 | 2014-03-26 | 安徽恒星制药有限公司 | Industrial production method of high-purity sulfuric acid terbutaline |
| CN109988074A (en) * | 2018-06-01 | 2019-07-09 | 药璞(上海)医药科技有限公司 | A kind of preparation method being suitble to medicinal terbutaline sulphate crystal B |
| US20220402861A1 (en) * | 2020-03-02 | 2022-12-22 | Wen Tan | A Crystalline form of (R)-terbutaline Hydrochloride |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1830951A (en) * | 2006-04-21 | 2006-09-13 | 华南农业大学 | Method for preparing (+-)-alpha-[(substituted amino) methyl]-benzene ring substituted group-phenylmethanol type compounds |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1830951A (en) * | 2006-04-21 | 2006-09-13 | 华南农业大学 | Method for preparing (+-)-alpha-[(substituted amino) methyl]-benzene ring substituted group-phenylmethanol type compounds |
Non-Patent Citations (4)
| Title |
|---|
| DESIGN》.2008,第8卷(第1期),80-90. * |
| Robin K. Harris等.Characterization of Polymorphs and Solvates of Terbutaline Sulfate.《CRYSTAL GROWTH & DESIGN》.2008,第8卷(第1期),80-90. |
| Robin K. Harris等.Characterization of Polymorphs and Solvates of Terbutaline Sulfate.《CRYSTAL GROWTH & * |
| 殷敦祥等.硫酸特布他林的合成.《中国医药工业杂志》.1999,第30卷(第1期),4-6. * |
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