CN109988212A - A kind of Inflamase production method - Google Patents
A kind of Inflamase production method Download PDFInfo
- Publication number
- CN109988212A CN109988212A CN201910322636.0A CN201910322636A CN109988212A CN 109988212 A CN109988212 A CN 109988212A CN 201910322636 A CN201910322636 A CN 201910322636A CN 109988212 A CN109988212 A CN 109988212A
- Authority
- CN
- China
- Prior art keywords
- acetone
- inflamase
- water
- production method
- prednisolone phosphate
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J51/00—Normal steroids with unmodified cyclopenta(a)hydrophenanthrene skeleton not provided for in groups C07J1/00 - C07J43/00
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
A kind of Inflamase production method dissolves prednisolone phosphate with the mixed solution of acetone and water using prednisolone phosphate as raw material, sodium hydrate aqueous solution is added dropwise into tank, temperature controls 10-25 DEG C, pH value is adjusted to 9.0-9.5, stirring, filtering after repetition measurement pH value is constant, is pumped into acetone in thinning tank, temperature adjustment, is added reaction solution, and mass crystallization is precipitated in stirring, no less than 8 hours are stood to discharge, it is dry to get rid of after discharging is washed with acetone, Inflamase is dried to obtain after must expecting.The a variety of solvents of traditional handicraft are changed to single solvent by this method, solve the diversified bottleneck of residual solvent in bulk pharmaceutical chemicals, and drying time shortens half the time, and the total impurities that the present processes obtain have greater advantage less than 2.0% in quality.
Description
Technical field
The present invention relates to drug production technology, in particular to a kind of Inflamase belongs to system at salt production method
Medicine technical field.
Background technique
Inflamase clinical application purposes is Aeroseb-Dex.With anti-inflammatory, antiallergy and inhibition
The multiple pharmacological effects such as immune.Anti-inflammatory effect: glucocorticoid mitigates and prevents reaction of the tissue to inflammation, to mitigate inflammation
Performance.Immunosuppressive action: the immune response of cell intermediary, the allergic reaction of retardance are prevented or inhibited, and is mitigated primary
The extension of immune response.Antitoxin, Antishock function: glucocorticoid can subtract to Nnti-Bacterial endotoxin to the stimulate the reaction of body
Light cellular damage plays the effect of protection body.A kind of prednisolone phosphoric acid of applicant's China Patent No. 201310539987.X(
The production technology technique of sodium) in disclose a kind of Inflamase into the technique of salt, which is widely used in producing in the past.
But with the development of situation, following problem is produced using the technique, in the technique, is first dissolved using methanol, then
It is added in Ethanol tank, a variety of solvents has been used during production, so containing methanol in waste liquid last in the technique
And ethyl alcohol, this mixed solvent is unable to recovery, and the mixed liquor of methanol and ethyl alcohol is difficult to separate, and needs to adopt if separation
With high-purity rectification tower, the investment of high-purity rectification tower is very big, if being merely high-purity in the purpose for separate this waste material
The recycling rectifying column returns of investment of degree be for enterprise it is not cost-effective, it is very big to will lead to enterprise operation increased costs, but to warp
Ji benefit is not just being contributed, moreover the strict control of environmental protection does not allow this kind of waste liquid arbitrarily to discharge at present, so using should
The processing of this waste liquid generated after technique production is the very hang-up that enterprise faces, and enterprise can only be given up these using holding vessel
Liquid is temporary, but also can only be meter for the time being, and there are also a variety of solvents used in the technique, to cause the solvent in end product residual
Stay diversification.And ethyl alcohol due to boiling point be 78.4 DEG C, the time is long in the drying process, can generate more impurity, the technique
In the impurity content that finally obtains between 1.5-2.5%, influence steroidal quality.
Summary of the invention
It is an object of the invention to overcome current Inflamase at salt produce present in the above problem, provide
A kind of Inflamase is at salt production method.
To achieve the purpose of the present invention, using following technical solutions: a kind of Inflamase production method, with
Prednisolone phosphate is raw material, dissolves prednisolone phosphate with the mixed solution of acetone and water, hydroxide is added dropwise into tank
Sodium water solution, temperature control 10-25 DEG C, pH value are adjusted to 9.0-9.5, stir, filtering after repetition measurement pH value is constant, in thinning tank
It is pumped into acetone, reaction solution is added in temperature adjustment, and mass crystallization is precipitated in stirring, and it stands no less than 8 hours and discharges, after discharging is washed with acetone,
It is dry to get rid of, Inflamase is dried to obtain after must expecting, further, the volume of acetone and water in the mixed solution of acetone and water
Than for 1-3:2-6, the mixed solvent used further, is pumped into acetone for 6-10 times of prednisolone phosphate in thinning tank
Amount be 15-20 times of prednisolone phosphate.
Positive advantageous effects of the invention are: a variety of solvents of traditional handicraft are changed to single solvent by this method, solution
The diversified bottleneck of residual solvent certainly in bulk pharmaceutical chemicals ensure that drug safety, while the recycling that this single solvent can be convenient
It applies, basically will not produce discharging of waste liquid, environmental protection also mitigates pressure, and the solvent use herein arrived is acetone, has
Low boiling point, volatile, drying time short feature improves product quality, shortens drying process time, the steroidal matter of guarantee
Amount.Because the application method uses acetone, 56.63 DEG C of low boiling point, structure is simply volatile, and boiling point differs 21.77 DEG C, the patent No.
201310539987.X technique drying time is 4-8 days, and the present processes drying time is 3-4 days, and drying time shortens one
Half time, drying time have apparent advantage.In the production of this kind of drug, the generation of impurity and drying time length have just
Compare functional relation, that is to say, that the dry time is longer, and total impurities are bigger, and quality is poorer, so this method drying time is short
If have greater advantage in Control of Impurities, the product total impurities for using the technique of patent No. 201310539987.X to obtain for
1.5-2.5%, for the total impurities that the present processes obtain less than 2.0%, most low energy reaches 1.0% hereinafter, the application in quality
Method occupies greater advantage.
Specific embodiment
In order to more fully explain implementation of the invention, embodiment of the invention is provided, these embodiments are only
To elaboration of the invention, do not limit the scope of the invention.
Prednisolone phosphate is fixed material in the present invention, is measured with g, liquid material is measured with ml, with prednisolone
The multiple ratio of phosphate is ml:g.
Embodiment 1:
Claim 100g prednisolone phosphate, is dissolved in the in the mixed solvent of 8 times of acetone and water, in the mixed solution of acetone and water
The volume ratio of acetone and water is 1:2, and with sodium hydrate aqueous solution tune pH value to 9.5, temperature controls 10-15 DEG C, filters feed liquid.Material
Liquid dilutes in the acetone of 25 times of ratios, stands 9 hours after stirring to get mass crystallization, filters, dry after must expecting, total impurities
1.3%, product quality meets the standard of EP9.0, USP39.
Embodiment 2:
Claim 100g prednisolone phosphate, is dissolved in the in the mixed solvent of 10 times of acetone and water, the mixed solution of acetone and water
The volume ratio of middle acetone and water is 3:2, and with sodium hydrate aqueous solution tune pH value to 9.2, temperature controls 15-20 DEG C, filters feed liquid.
Feed liquid dilutes in the acetone of 20 times of ratios, stands 8.5 hours after stirring to get mass crystallization, filters, dry after must expecting, impurity is total
Amount 1.5%, product quality meets the standard of EP9.0, USP39.
Embodiment 3:
Claim 100g prednisolone phosphate, is dissolved in 7 acetone and the in the mixed solvent of water, third in the mixed solution of acetone and water
The volume ratio of ketone and water is 1.5:6, and with sodium hydrate aqueous solution tune pH value to 9.3, temperature controls 20-25 DEG C, filters feed liquid.Material
Liquid dilutes in the acetone of 16 times of ratios, stands 8 hours after stirring to get mass crystallization, filters, dry after must expecting, total impurities
1.6%, product quality meets the standard of EP9.0, USP39.
Embodiment 4:
Claim 100g prednisolone phosphate, is dissolved in the in the mixed solvent of 70 times of acetone and water, the mixed solution of acetone and water
The volume ratio of middle acetone and water is 3:5, and with sodium hydrate aqueous solution tune pH value to 9.2, temperature controls 20-25 DEG C, filters feed liquid.
Feed liquid dilutes in the acetone of 16 times of ratios, stands 8 hours after stirring to get mass crystallization, filters, dry after must expecting, total impurities
0.98%, product quality meets the standard of EP9.0, USP39.
After the embodiment that the present invention will be described in detail, one of ordinary skilled in the art is clearly understood that, is not being taken off
It is lower from above-mentioned claim and spirit to carry out various change and modify, it is all according to the technical essence of the invention to the above reality
Any simple modification, equivalent change and modification made by example are applied, belong to the range of technical solution of the present invention, and the present invention is also not
It is limited to the embodiment of example in specification.
Claims (3)
1. a kind of Inflamase production method, using prednisolone phosphate as raw material, it is characterised in that: use acetone and water
Mixed solution dissolve prednisolone phosphate, be added dropwise sodium hydrate aqueous solution into tank, temperature controls 10-25 DEG C, by pH value
It is adjusted to 9.0-9.5, is stirred, filtering after repetition measurement pH value is constant is pumped into acetone in thinning tank, and reaction solution, stirring analysis is added in temperature adjustment
Mass crystallization out stands no less than 8 hours and discharges, dry to get rid of after discharging is washed with acetone, and prednisolone phosphoric acid is dried to obtain after must expecting
Sodium.
2. a kind of Inflamase production method according to claim 1, it is characterised in that: the mixing of acetone and water
The volume ratio of acetone and water is 1:3-2:6 in solution, and the mixed solvent used is 6-10 times of prednisolone phosphate.
3. a kind of Inflamase production method according to claim 1, it is characterised in that: be pumped into third in thinning tank
The amount of ketone is 15-20 times of prednisolone phosphate.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201910322636.0A CN109988212B (en) | 2019-04-22 | 2019-04-22 | Prednisolone sodium phosphate production method |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201910322636.0A CN109988212B (en) | 2019-04-22 | 2019-04-22 | Prednisolone sodium phosphate production method |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN109988212A true CN109988212A (en) | 2019-07-09 |
| CN109988212B CN109988212B (en) | 2020-11-20 |
Family
ID=67134988
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201910322636.0A Active CN109988212B (en) | 2019-04-22 | 2019-04-22 | Prednisolone sodium phosphate production method |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN109988212B (en) |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN112094311A (en) * | 2020-10-16 | 2020-12-18 | 西安国康瑞金制药有限公司 | Process for preparing dexamethasone sodium phosphate by one-step method |
| CN112457361A (en) * | 2020-11-26 | 2021-03-09 | 河南利华制药有限公司 | Method for recovering prednisolone sodium phosphate mother liquor |
| CN115181155A (en) * | 2022-07-27 | 2022-10-14 | 河南利华制药有限公司 | Preparation method of high-standard prednisolone sodium phosphate |
Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB902254A (en) * | 1957-11-19 | 1962-08-01 | Glaxo Lab Ltd | Improvements in or relating to the preparation of steroid derivatives |
| GB1461663A (en) * | 1974-01-04 | 1977-01-19 | Lark Spa | Process for the preparation of 17-esters of 17alpha,21-dihydroxy steroids of the pregnane series and products obtained |
| CN101742987A (en) * | 2007-05-16 | 2010-06-16 | 霍维奥恩联合有限公司 | Be used to obtain the method for steroidal phosphate compounds |
| CN104610414A (en) * | 2013-11-05 | 2015-05-13 | 河南利华制药有限公司 | Prednisolone sodium phosphate production technology |
| CN104610413A (en) * | 2013-11-05 | 2015-05-13 | 河南利华制药有限公司 | Prednisolone phosphate purifying technology |
| CN105294810A (en) * | 2014-07-16 | 2016-02-03 | 河南利华制药有限公司 | Process for producing high-standard prednisolone sodium phosphate |
-
2019
- 2019-04-22 CN CN201910322636.0A patent/CN109988212B/en active Active
Patent Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB902254A (en) * | 1957-11-19 | 1962-08-01 | Glaxo Lab Ltd | Improvements in or relating to the preparation of steroid derivatives |
| GB1461663A (en) * | 1974-01-04 | 1977-01-19 | Lark Spa | Process for the preparation of 17-esters of 17alpha,21-dihydroxy steroids of the pregnane series and products obtained |
| CN101742987A (en) * | 2007-05-16 | 2010-06-16 | 霍维奥恩联合有限公司 | Be used to obtain the method for steroidal phosphate compounds |
| CN104610414A (en) * | 2013-11-05 | 2015-05-13 | 河南利华制药有限公司 | Prednisolone sodium phosphate production technology |
| CN104610413A (en) * | 2013-11-05 | 2015-05-13 | 河南利华制药有限公司 | Prednisolone phosphate purifying technology |
| CN105294810A (en) * | 2014-07-16 | 2016-02-03 | 河南利华制药有限公司 | Process for producing high-standard prednisolone sodium phosphate |
Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN112094311A (en) * | 2020-10-16 | 2020-12-18 | 西安国康瑞金制药有限公司 | Process for preparing dexamethasone sodium phosphate by one-step method |
| CN112094311B (en) * | 2020-10-16 | 2022-04-08 | 西安国康瑞金制药有限公司 | Process for preparing dexamethasone sodium phosphate by one-step method |
| CN112457361A (en) * | 2020-11-26 | 2021-03-09 | 河南利华制药有限公司 | Method for recovering prednisolone sodium phosphate mother liquor |
| CN112457361B (en) * | 2020-11-26 | 2021-12-07 | 河南利华制药有限公司 | Method for recovering prednisolone sodium phosphate mother liquor |
| CN115181155A (en) * | 2022-07-27 | 2022-10-14 | 河南利华制药有限公司 | Preparation method of high-standard prednisolone sodium phosphate |
| CN115181155B (en) * | 2022-07-27 | 2023-08-15 | 河南利华制药有限公司 | Preparation method of prednisolone sodium phosphate |
Also Published As
| Publication number | Publication date |
|---|---|
| CN109988212B (en) | 2020-11-20 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN109988212A (en) | A kind of Inflamase production method | |
| US2959500A (en) | Process for the saccharification of cellulose and cellulosic materials | |
| JPH0476361B2 (en) | ||
| CN104710483B (en) | A kind of preparation method of Glucosamine Sulphate | |
| KR20160030483A (en) | Process for manufacturing lithium carboxymethyl cellulose | |
| CN108033900A (en) | A kind of discoloration method of three nitrile of 1,3,6- hexanes | |
| CN111087434A (en) | Extraction method of hesperidin | |
| CN106831503A (en) | A kind of preparation method of Terephthalidene Dicamphor Sulfonic Acid's sun-screening agent | |
| CN106905406A (en) | A kind of preparation technology of Triamcinolone acetonide | |
| CN112409498A (en) | Preparation method of high-stability carboxymethyl hydroxyethyl cellulose | |
| CN115155108A (en) | Method for purifying silver nitrate by adopting ion exchange resin | |
| CN108034780B (en) | Tanning-assisting dyeing assistant, preparation method and application thereof | |
| CN102492747B (en) | Method for enzymatically preparing and separating L-aspartate and ammonium sulfate as byproduct thereof | |
| GB1153560A (en) | Improved Cellulose Triacetate and process for its production | |
| CN106632699A (en) | Preparation method of high-transparency hydroxy ethyl cellulose (HEC) | |
| CN114249343B (en) | Production method of calcium hydroxide | |
| CN106674355A (en) | Method for preparing hydroxyethyl cellulose by using 20-30% alkali liquid | |
| CN103113268B (en) | The preparation method of sulfonic acid iron and alcoholic solution thereof | |
| US2969355A (en) | Method of preparing cellulose sulfate | |
| CN102875686A (en) | Preparation method of cellulose acetate butyrate | |
| CN102154875A (en) | Pulping technology of cotton linter | |
| AU644614B2 (en) | Process for the recovery of gallium from basic solutions containing it | |
| CN104926660B (en) | The green synthesis method of a kind of trinitrophloroglucinol and application | |
| WO2022223058A2 (en) | Betamethasone sodium phosphate crystal, and preparation method therefor and use thereof | |
| CN106129441A (en) | The cleaning fast preparation method of a kind of vanadium oxysulfate solution and purposes |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant |