CN104262649A - Sodium croscarmellose and preparation method thereof - Google Patents
Sodium croscarmellose and preparation method thereof Download PDFInfo
- Publication number
- CN104262649A CN104262649A CN201410507872.7A CN201410507872A CN104262649A CN 104262649 A CN104262649 A CN 104262649A CN 201410507872 A CN201410507872 A CN 201410507872A CN 104262649 A CN104262649 A CN 104262649A
- Authority
- CN
- China
- Prior art keywords
- preparation
- solvent
- reaction
- propylene glycol
- mucine
- 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.)
- Pending
Links
Abstract
The invention belongs to the chemical field, in particular relates to sodium croscarmellose and a preparation method thereof and aims at solving the technical problem of providing a preparation method of sodium croscarmellose. The technical scheme adopted by the invention is as follows: the preparation method of sodium croscarmellose comprises the following steps: uniformly dispersing sodium croscarmellose in a solvent, regulating pH to 1.0-3.0, adding a cross-linking agent, reacting, cooling and removing impurities, wherein the cross-linking agent is propylene glycol. The sodium croscarmellose prepared by the method has the characteristics such as excellent disintegration property, suspension property and no toxicity, and can be well used in the pharmaceutical field.
Description
Technical field
The invention belongs to chemical field, be specifically related to a kind of croscarmellose sodium and preparation method thereof.
Background technology
Along with the development of pharmaceutical industries and people are to the attention of food, drug safety health, the supervision of FDA to medical auxiliary materials is also more and more stricter, especially, after " the toxic capsule event " of outburst in 2012, boosting is excellent, development and production that is nontoxic, high performance medical auxiliary materials.Croscarmellose sodium has the characteristics such as excellent slaking, suspension ability, nontoxicity.Owing to there being the existence of cross-link bond, it is water insoluble, has very strong water absorbability in water, can absorb the water being several times as much as itself weight and expands and do not dissolve.In pharmaceutical industry, be used as disintegrating agent, suspensoid and weighting agent in a large number, improve dissolution rate and the bioavailability of medicine, be mainly used in children, old man's medication and Chinese medicinal granular formulation.
Summary of the invention
First technical problem to be solved by this invention is to provide a kind of preparation method of croscarmellose sodium.The method comprises the following steps: Xylo-Mucine is in a solvent dispersed, adjusts pH to 1.0 ~ 3.0, adds linking agent, reaction, cooling, removal of impurities; Wherein, described linking agent is propylene glycol.
Concrete, aforesaid method comprises the following steps:
A, dispersed: Xylo-Mucine is in a solvent dispersed;
B, reaction: add sulphur acid for adjusting pH to 1.0 ~ 3.0, then react 20 ~ 30min in 38 ~ 42 DEG C after adding propylene glycol, 58 ~ 62 DEG C of reaction 1.5 ~ 2h, 68 ~ 72 reaction 20 ~ 30min;
C, aftertreatment: cooling, except desolventizing, removing sulfuric acid.
Preferably, in aforesaid method step a, the substitution value of described Xylo-Mucine is 0.8 ~ 0.9.
Concrete, in aforesaid method step a, by weight, Suo methylcellulose gum Na ︰ solvent=1 ︰ 8 ~ 12.
Preferably, in aforesaid method step a, described solvent is at least one in ethanol, Virahol.
Further, in aforesaid method step a, water content≤5% of described solvent.
Preferably, in aforesaid method step a, the described dispersed mode adopting stirring.Further, churning time is 10 ~ 20min, and stirring velocity is 180 ~ 220r/min.
Preferably, in aforesaid method step b, water content≤10% of described sulfuric acid.
Preferably, in aforesaid method step b, by weight, the amount of the propylene glycol added is Bing bis-Chun ︰ Xylo-Mucine=1 ︰ 5 ~ 15.
Concrete, aforesaid method step c is: aftertreatment: after cooling, and solid-liquid separation adds cleaning solvent in solid, then regulates pH to 5.0 ~ 7.0 with alkali, solid-liquid separation, then washs solid with cleaning solvent, solid drying.
Preferably, in aforesaid method step c, described alkali be in sodium hydroxide, potassium hydroxide any one.
Preferably, in aforesaid method step c, described cleaning solvent is ethanol.
Further, in aforesaid method step c, the concentration of described ethanol is 60 ~ 65%.
Preferably, in aforesaid method step c, drying temperature is 60 ~ 80 DEG C, and time of drying is 18 ~ 24h.
Second technical problem to be solved by this invention is to provide the croscarmellose sodium that aforesaid method is prepared.
The croscarmellose sodium that the inventive method is prepared not only meets Chinese Pharmacopoeia 2010 editions (CP2010), quality product is suitable with external product simultaneously, there is the characteristics such as excellent slaking, suspension ability, nontoxicity, be applicable to pharmaceutical auxiliaries, have a good application prospect.
Embodiment
A preparation method for croscarmellose sodium, comprises the following steps:
A, dispersed: Xylo-Mucine is in a solvent dispersed;
B, reaction: add sulphur acid for adjusting pH to 1.0 ~ 3.0, then react 20 ~ 30min in 38 ~ 42 DEG C after adding propylene glycol, 58 ~ 62 DEG C of reaction 1.5 ~ 2h, 68 ~ 72 reaction 20 ~ 30min;
C, aftertreatment: cooling, except desolventizing, removing sulfuric acid.
Preferably, in aforesaid method step a, the substitution value of described Xylo-Mucine is 0.8 ~ 0.9.
Concrete, in aforesaid method step a, by weight, Suo methylcellulose gum Na ︰ solvent=1 ︰ 8 ~ 12.
Preferably, in aforesaid method step a, described solvent is at least one in ethanol, Virahol.
Further, in aforesaid method step a, water content≤5% of described solvent.
Preferably, in aforesaid method step a, the described dispersed mode adopting stirring.Further, churning time is 10 ~ 20min, and stirring velocity is 180 ~ 220r/min.
The sulfuric acid added is not only in order to adjust ph, in order to linking agent can be cross-linked under its suitable pH value; And the sulfuric acid added also makees the catalyzer of crosslinking reaction, so, water content≤10% of preferably sulfuric acid.
Preferably, in aforesaid method step b, by weight, the amount of the propylene glycol added is Bing bis-Chun ︰ Xylo-Mucine=1 ︰ 5 ~ 15.
After aforesaid method step a and b, obtain liquid-solid mixture, pH value is 1 ~ 3, can to add in alkali and after solid-liquid separation again, but in order to reduce alkali consumption, preferred first solid-liquid separation; After solid-liquid separation, in solid, a small amount of acid may being remained, can neutralize with adding alkali after alcohols material dispersion products more again, and then solid-liquid separation.So concrete, aforesaid method step c is: aftertreatment: after cooling, and solid-liquid separation adds cleaning solvent in solid, then regulate pH to 5.0 ~ 7.0 with alkali, solid-liquid separation, then wash solid with cleaning solvent, solid drying.
Solid-liquid separation described in the inventive method can adopt conventional separation method, as centrifugal, filtration etc.
Preferably, in aforesaid method step c, described alkali be in sodium hydroxide, potassium hydroxide any one.
Preferably, in aforesaid method step c, described cleaning solvent is ethanol.
Further, in aforesaid method step c, the concentration of described ethanol is 60 ~ 65%.
Preferably, in aforesaid method step c, drying temperature is 60 ~ 80 DEG C, and time of drying is 18 ~ 24h.
By above-mentioned steps, the croscarmellose sodium structural formula prepared is as follows:
Chinese Pharmacopoeia 2010 editions (CP2010) product all technicals can be used for the quality evaluating product quality, and specific targets see the following form 1:
Table 1 croscarmellose sodium technical indicator
| Sequence number | Project | Index |
| 1 | Substitution value | 0.65～0.85 |
| 2 | Settling volume | 10.0～30.0mL |
| 3 | Residue on ignition | 14.0～28.0％ |
| 4 | Potential of hydrogen | 5.0～7.0 |
| 5 | Heavy metal | ≤10ppm |
| 6 | Solute in water | ≤10.0％ |
| 7 | Sodium-chlor and sodium glycolate | ≤0.5％ |
| 8 | Weight loss on drying | ≤10.0％ |
Croscarmellose sodium is as cellulose-type super-disintegrant, suspensoid and weighting agent, and settling volume is its important judgement criteria.
Xylo-Mucine (the food grade adopted in embodiment, substitution value 0.89), ethanol (concentration 95.0%), Virahol (analytical pure), propylene glycol (analytical pure), the vitriol oil (concentration 98.1%), cleaning solvent alcohol concn (64.5%).
Test example 1
The present inventor has carried out a large amount of screenings according to the performance index of the product prepared after utilizing different linking agent to the selection of linking agent, and partial data sees the following form 2:
Adopt the polyfunctional group materials such as trichloro-butyl alcohol, dichlorohydrine, propylene glycol, Succinic anhydried, according to functional group's active situation at different conditions, carry out CMC crosslinking assays at different conditions respectively.
The testing program of the different linking agent of table 2 and test-results
Can find out that trichloro-butyl alcohol, dichlorohydrine are poorer as the test-results of linking agent than propylene glycol, Succinic anhydried as the test-results of linking agent from above test-results, and dichlorohydrine is not high at the degree of being widely used of medicine synthesis and food service industry.Therefore the test effect of primary comparison propylene glycol and Succinic anhydried.
Table 3 propylene glycol and Succinic anhydried controlled trial the key technical indexes
As can be seen from Table 3, when making linking agent with Succinic anhydried and propylene glycol respectively, under identical processing condition, the test effect of propylene glycol is better, product meets Chinese Pharmacopoeia 2010 editions (CP2010), and is close with external high-quality croscarmellose sodium (German JRS and U.S. FMC) all technical.
Embodiment 1
In the glass reaction still of 2000mL, add the Xylo-Mucine of 100 parts, 1000 parts of ethanol, stir 20min, be uniformly dispersed, add the vitriol oil and regulate pH=1.1, add 10 parts of propylene glycol, be warming up to 40 DEG C of insulation reaction 0.5h; Be warming up to 60 DEG C of insulation reaction 2h; Be warming up to 70 DEG C of insulation reaction 0.5h, after reaction terminates, be cooled to 30 DEG C, discharging.After centrifugation, in solid phase, add 64.7% ethanol, regulate pH=6.5 with sodium hydroxide, after centrifugation, the washing with alcohol solid phase with 64.7% 2 times.Sample is dried 24h at 70 DEG C, obtains croscarmellose sodium product.
Embodiment 2
The Xylo-Mucine of 100 parts, 800 parts of Virahol-ethanol (mass ratio 1 ︰ 1) mixing solutionss are added in the glass reaction still of 2000mL, stir 15min, be uniformly dispersed, add the vitriol oil and regulate pH=1.5, add 12.5 parts of propylene glycol, be warming up to 40 DEG C of insulation reaction 0.5h; Be warming up to 60 DEG C of insulation reaction 2h; Be warming up to 70 DEG C of insulation reaction 0.5h.30 DEG C are cooled to, discharging after reaction terminates.After centrifugation, in solid phase, add 62.4% ethanol, regulate pH=5.8 with sodium hydroxide, after centrifugation, the washing with alcohol solid phase with 62.4% 2 times.Sample is dried 24h at 75 DEG C, obtains croscarmellose sodium product.
Embodiment 3
In the reactor of 50L, add the Xylo-Mucine of 2000 parts, 24000 parts of ethanol, stir 20min, be uniformly dispersed.Add the vitriol oil and regulate pH=1.4, add 135 parts of propylene glycol, be warming up to 40 DEG C of insulation reaction 0.5h; Be warming up to 60 DEG C of insulation reaction 2h; Be warming up to 70 DEG C of insulation reaction 0.5h.30 DEG C are cooled to, discharging after reaction terminates.After centrifugation, in solid phase, add 65.0% ethanol, regulate pH=6.0 with sodium hydroxide, after centrifugation, the washing with alcohol solid phase with 65.0% 2 times.Sample is dried 24h at 70 DEG C, obtains croscarmellose sodium product.
Sample analysis result in embodiment is as following table 4.
Table 4 analytical results
In summary, the croscarmellose sodium prepared by the inventive method has the characteristics such as excellent slaking, suspension ability, nontoxicity, can be advantageously applied to pharmacy field.
Claims (9)
1. a preparation method for croscarmellose sodium, is characterized in that: Xylo-Mucine is in a solvent dispersed, adjusts pH to 1.0 ~ 3.0, adds linking agent, reaction, cooling, removal of impurities; Wherein, described linking agent is propylene glycol.
2. preparation method according to claim 1, is characterized in that: comprise the following steps:
A, dispersed: Xylo-Mucine is in a solvent dispersed;
B, reaction: add sulphur acid for adjusting pH to 1.0 ~ 3.0, then react 20 ~ 30min in 38 ~ 42 DEG C after adding propylene glycol, 58 ~ 62 DEG C of reaction 1.5 ~ 2h, 68 ~ 72 reaction 20 ~ 30min;
C, aftertreatment: cooling, except desolventizing, removing sulfuric acid.
3. preparation method according to claim 2, is characterized in that: in step a, and the substitution value of described Xylo-Mucine is 0.8 ~ 0.9.
4. preparation method according to claim 2, is characterized in that: in step a, by weight, and Suo methylcellulose gum Na ︰ solvent=1 ︰ 8 ~ 12.
5. preparation method according to claim 2, is characterized in that: described solvent is at least one in ethanol, Virahol.
6. preparation method according to claim 2, is characterized in that: in step a, water content≤5% of described solvent.
7. preparation method according to claim 2, is characterized in that: in step b, water content≤10% of described sulfuric acid.
8. preparation method according to claim 2, is characterized in that: in step b, and by weight, the amount of the propylene glycol added is Bing bis-Chun ︰ Xylo-Mucine=1 ︰ 5 ~ 15.
9. the croscarmellose sodium prepared by the preparation method described in any one of claim 1 ~ 8.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201410507872.7A CN104262649A (en) | 2014-09-28 | 2014-09-28 | Sodium croscarmellose and preparation method thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201410507872.7A CN104262649A (en) | 2014-09-28 | 2014-09-28 | Sodium croscarmellose and preparation method thereof |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN104262649A true CN104262649A (en) | 2015-01-07 |
Family
ID=52154250
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201410507872.7A Pending CN104262649A (en) | 2014-09-28 | 2014-09-28 | Sodium croscarmellose and preparation method thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN104262649A (en) |
Citations (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1139437A (en) * | 1993-10-29 | 1997-01-01 | 金伯利-克拉克公司 | Modified polysaccharides having improved absorbent properties and process for the preparation thereof |
| CN101967232A (en) * | 2010-09-28 | 2011-02-09 | 徐国财 | Preparation method of croscarmellose sodium |
| CN102093481A (en) * | 2009-12-10 | 2011-06-15 | 上海长光企业发展有限公司 | Method for preparing instant carboxymethylcellulose |
| CN102295706A (en) * | 2011-09-05 | 2011-12-28 | 安徽山河药用辅料股份有限公司 | Method for preparing croscarmellose sodium medicinal auxiliary material by using wood fibers |
| CN102580136A (en) * | 2011-01-07 | 2012-07-18 | 佛山市优特医疗科技有限公司 | High absorbent wound dressing capable of being removed entirely |
| CN102604131A (en) * | 2012-02-27 | 2012-07-25 | 浙江中维药业有限公司 | Preparation method of cross-linked sodium carboxymethyl cellulose |
| CN103059321A (en) * | 2013-01-25 | 2013-04-24 | 湖北葛店人福药用辅料有限责任公司 | Preparation method of cross-linking sodium carboxymethylcellulose pharmaceutical adjuvant |
-
2014
- 2014-09-28 CN CN201410507872.7A patent/CN104262649A/en active Pending
Patent Citations (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1139437A (en) * | 1993-10-29 | 1997-01-01 | 金伯利-克拉克公司 | Modified polysaccharides having improved absorbent properties and process for the preparation thereof |
| CN102093481A (en) * | 2009-12-10 | 2011-06-15 | 上海长光企业发展有限公司 | Method for preparing instant carboxymethylcellulose |
| CN101967232A (en) * | 2010-09-28 | 2011-02-09 | 徐国财 | Preparation method of croscarmellose sodium |
| CN102580136A (en) * | 2011-01-07 | 2012-07-18 | 佛山市优特医疗科技有限公司 | High absorbent wound dressing capable of being removed entirely |
| CN102295706A (en) * | 2011-09-05 | 2011-12-28 | 安徽山河药用辅料股份有限公司 | Method for preparing croscarmellose sodium medicinal auxiliary material by using wood fibers |
| CN102604131A (en) * | 2012-02-27 | 2012-07-25 | 浙江中维药业有限公司 | Preparation method of cross-linked sodium carboxymethyl cellulose |
| CN103059321A (en) * | 2013-01-25 | 2013-04-24 | 湖北葛店人福药用辅料有限责任公司 | Preparation method of cross-linking sodium carboxymethylcellulose pharmaceutical adjuvant |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN105434362B (en) | The preparation method of high-purity granular pattern Amprolium Hydrochloride | |
| CN104177461A (en) | Preparation method of troxerutin | |
| CN105085692B (en) | The preparation method of Ac-Di-Sol | |
| JP2017082211A (en) | Pore water-soluble nonionic cellulose ether excellent in solubility and method of producing the same | |
| US6602995B2 (en) | Method for the formation of low-substituted hydroxypropyl cellulose particles | |
| CN106889625A (en) | A kind of preparation method of inulin particle | |
| EP3521317A1 (en) | Method for producing water-soluble hydroxyethyl cellulose | |
| CN104262649A (en) | Sodium croscarmellose and preparation method thereof | |
| CN106883202B (en) | A kind of preparation method of Ascorbyl Palmitate | |
| EP2736614B1 (en) | Method of removing alkylene halogenohydrin from cellulose ether | |
| JP2021534225A (en) | Method for purifying crude rocuronium bromide | |
| CN110172060A (en) | Razaxaban, synthesis and refining methd | |
| CN105481791A (en) | Acotiamide hydrochloride dihydrate crystal, and preparation method and applications thereof | |
| CN106518867B (en) | A kind of process for purification of Eliquis | |
| CN105012237A (en) | Fluticasone furoate nasal spray and preparation method thereof | |
| CN104557689A (en) | Method for preparing 4-[4-({[4-chloro-3-(trifluoromethyl) phenyl] carbamyl} amino)-3-fluorophenoxy]-N-methylpyridine-2-formamide and hydrate thereof | |
| CN104774158A (en) | Novel preparation method for ornithine aspartate | |
| CN104326954A (en) | Synthesis method of fudosteine | |
| CN108066300A (en) | A kind of glipizide tablet and preparation method thereof | |
| CN104974146B (en) | Crystal formation E, crystal formation F of canagliflozin and preparation method thereof | |
| CN112608388A (en) | Refining method of sodium carboxymethylcellulose for injection | |
| CN104402703B (en) | A kind of synthetic method of acrylate chloride | |
| CN108485144A (en) | The method for preparing biomass-based stabilizer using forest and agricultural biomass | |
| CN107325333A (en) | Instant hydroxyethyl cellulose and preparation method thereof | |
| CN116251065B (en) | APTM soluble powder intermediate, soluble powder and preparation method |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| RJ01 | Rejection of invention patent application after publication |
Application publication date: 20150107 |
|
| RJ01 | Rejection of invention patent application after publication |