CN105924331B - A kind of process for purification of propane diols - Google Patents
A kind of process for purification of propane diols Download PDFInfo
- Publication number
- CN105924331B CN105924331B CN201610271714.5A CN201610271714A CN105924331B CN 105924331 B CN105924331 B CN 105924331B CN 201610271714 A CN201610271714 A CN 201610271714A CN 105924331 B CN105924331 B CN 105924331B
- Authority
- CN
- China
- Prior art keywords
- propane diols
- extraction
- tower
- impurity
- crude product
- 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.)
- Active
Links
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C29/00—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom not belonging to a six-membered aromatic ring
- C07C29/74—Separation; Purification; Use of additives, e.g. for stabilisation
- C07C29/76—Separation; Purification; Use of additives, e.g. for stabilisation by physical treatment
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C29/00—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom not belonging to a six-membered aromatic ring
- C07C29/74—Separation; Purification; Use of additives, e.g. for stabilisation
- C07C29/76—Separation; Purification; Use of additives, e.g. for stabilisation by physical treatment
- C07C29/86—Separation; Purification; Use of additives, e.g. for stabilisation by physical treatment by liquid-liquid treatment
Abstract
The invention discloses a kind of process for purification of propane diols, available for the preparation of injection, belong to field of medicaments, this method is comprised the following steps：（1）Initial filter；（2）Extraction；（3）Ultrafiltration.The beneficial effects of the invention are as follows：Product can be used for the preparation of injection, has wide range of applications, greatly reduces quality risk.
Description
Technical field
The invention discloses a kind of process for purification of propane diols, available for the preparation of injection, belong to field of medicaments.
Background technology
Injection is clinically played an important role with its unique curative effect, but simultaneously also along with many bad anti-
Should, receive much concern always.Increasing event shows that the problem of auxiliary material is caused in injection is many injection adverse reactions
Root, it might even be possible to cause group Adverse drug events.
Risk by cognition in the industry, but except bacterial endotoxin not caused by injection supplementary material bacterial endotoxin is undesirable
Caused by meeting the requirements outside risk, often caused safety risks are also manifested by contaminant overstandard to pharmaceutic adjuvant.
Injection propane diols refers to injection 1,2-PD, is a kind of widely used injection supplementary material.Injection
Propane diols is refining to obtain by technical grade, food-grade or medicinal grade propylene glycol.At present, the production technology of common propane diols has 5 kinds.
（1）Expoxy propane direct hydration method：In industrial production, propane diols is mainly hydrated by expoxy propane and produced.Expoxy propane is hydrated
When producing propane diols, DPG and tripropylene glycol and a small amount of higher glycol are produced simultaneously.（2）Expoxy propane indirect hydration
Method：It is made by expoxy propane with water with sulphur acid as catalyst indirect hydration.（3）Propylene Direct Catalytic Oxidation method.（4）Biochemical industry
Method：A, by raw material through chemical reaction of glycerine 1,3-PD is prepared, by glycerine and synthesized at 200 DEG C using Rh-W catalyst
Solid/liquid/gas reactions prepare 1,3- propane diols.B, with biological diesel oil byproduct glycerine produce propane diols.In producing under atmospheric pressure first
Mesosome pyruvic alcohol, then under copper-chromite catalyst effect, pyruvic alcohol hydrogenation production propane diols.C, using sorbierite as original
Material is cracked into the mixed alcohols such as propane diols, ethylene glycol and butanediol by high-temperature catalytic, then separating-purifying again.（5）, carbonic acid diformazan
Ester/propane diols co-production method：Ester exchange is carried out using propene carbonate and methanol, using sodium methoxide as catalyst, in atmospheric conditions
It is made.
2015 editions《Chinese Pharmacopoeia》Start to perform on December 1st, 2015, wherein newly-increased injection propane diols standard pair
Ethylene glycol impurity and bacterial endotoxin propose requirement.At present, most domestic propane diols manufacturer, still using original third
, there is following drawback in glycol production purification techniques：（1）Bacterial endotoxin and ethylene glycol can not be removed completely using prior art,
Injection stage requirement can not be met, such as Chinese patent CN101704719B discloses a kind of preparation method of medical-grade propylene glycol, should
Method prepares medical-grade propylene glycol by raw material of industrial grade propylene glycol, and preparation technology is simple, with low cost, but presence can not be effective
Remove propane diols and bacterial endotoxin, it is impossible to meet the problem of injection is required.（2）Even if indivedual optimizations of enterprises production work
Skill, can meet injection propane diols quality requirement, but still suffer from require raw material propane diols originate single, the unmanageable disadvantage of quality
End.
Due to propane diols wide material sources, material quality is uneven, and preparation technology differs, and is easily introduced in process of production miscellaneous
Matter, causes quality not reach statutory standards, and then increase the application risk of propane diols.The particularly security of injection propane diols
The drug safety of patient is directly connected to, it is insoluble to neglect.Ensure bacterial endotoxin in injection propane diols, product quality meets medicine
Allusion quotation requirement, it is one side to carry out Quality Control to finished product, and it is even more it in weighing to develop a kind of method of universal injection propane diols
Weight.
The content of the invention
To overcome in the prior art due to propane diols wide material sources, material quality is uneven, and preparation technology differs, in life
Impurity is easily introduced during production, causes quality not reach injection propane diols standard, the invention discloses a kind of essence of propane diols
Method processed is to solve the above problems.
The process for purification of propane diols of the present invention, is realized by the technical scheme comprised the steps of：1）Initial filter；（2）
Extraction；（3）Ultrafiltration.
The first step is initial filter step, by propane diols crude product through 0.45um membrane filtrations, to remove particle diameter in more than 0.45um
Impurity.
Propane diols crude product may introduce insoluble impurities during production, transport and use, and these impurity are through ultra filtration
Journey can also be removed.But it is higher that the content that there is the relatively low polar impurity of product such as DPG with ultrafiltration is directly extracted without initial filter
And milipore filter service life very low shortcoming.Found by applicant's long-felt and experiment, just filtering technology can be effective for increase
Solve the above problems.Its reason indiscriminate may can adsorb soluble impurity and propane diols for above-mentioned insoluble impurities, from
And cause the relatively low polar substances of extraction stages effectively to remove, while damaging milipore filter in ultra-filtration stage.
Second step is extraction, is comprised the following steps that：Propane diols crude product and extractant after initial filter are respectively from extraction tower I top
Portion and bottom enter, and tower top obtains extraction phase, and tower reactor obtains being more than containing polarized the propylene glycol solution of propane diols impurity, extraction phase
Into extraction tower II bottom, tower top is recycled extractant, and tower reactor obtains being less than containing polarized the extractant of propane diols impurity
Solution.
3rd step is ultrafiltration, takes the modified PS membrane ultrafiltration of raffinate phase method.Wherein modified polysulfone film is with N, N- dimethyl
Formamide is casting film solvent, according to polysulfones：Polyethylene glycol：Silica=15:1：2 mass ratio, adds the total matter of casting solution
The acylate or quaternary ammonium salt of amount 0.1 ~ 5%, are prepared through phase transfer method, and DMF is casting solution gross mass
75%.The one kind of described acylate in calcium sorbate, sorbic acid magnesium, potassium sorbate, sodium sorbate, described season
Ammonium salt selects one kind in normal-butyl trimethyl quaternary ammonium salt, tert-butyl group trimethyl quaternary ammonium salt, tetrem based quaternary ammonium salt.
Propane diols wide material sources, material quality is uneven, and preparation technology differs, and impurity is easily introduced in process of production,
Cause quality not reach statutory standards, and then increase the application risk of propane diols.Work is produced according to 5 kinds of common at present propane diols
Skill, existing propane diols process for refining can only be refined for the propane diols of wherein a kind or 2 kinds technique productions, and mainly be led to
Impurity is crossed in control crude product production process to control fine work quality, once propane diols crude product source changes, or crude product work
Deviation occurs for skill quality, can not effectively control, so as to substantially increase quality risk.Studied and found according to applicant, it is existing
There is impurity that may be present in technique to be divided into relatively low polar impurity and polarity of the polarity less than propane diols inclined higher than propane diols
Highly polar two kinds of impurity.The unmanageable impurity of existing process is mainly 1,3- propane diols and the pole that polarity is slightly below propane diols
Property higher than propane diols ethylene glycol, glycerine, sorbierite etc..
According to the research of applicant's long term test and grope find, using extraction process of the present invention, using with certain theory
The extraction tower of the number of plates, suitable extractant, flow velocity and at a temperature of, can be effective with certain mass ratio by extraction tower
Except depolarization is less than the impurity of propane diols.Wherein, the premise for reaching the effect is to use the method for the invention initial filter.
In addition, applicant chances in research process, can be except the endogenous toxic material that degerms using the PS membrane of special modification
Effectively except depolarization is more than the impurity of propane diols, such as ethylene glycol, sorbierite, glycerine while plain.
The innovation of the present invention is：
（1）There is provided a kind of process for purification of propane diols, product can be used for the preparation of injection, the process for purification after refining
It is not to be disclosed report.
（2）There is provided a kind of propane diols process for purification for being adapted to 5 kinds of propane diols sources, product can be used for injection after refining
Preparation, have wide range of applications, greatly reduce quality risk.
（3）Effectively it can be more than the side of the impurity of propane diols except depolarization while bacterial endotoxin is removed there is provided a kind of
Method.
Embodiment
The present invention program is further illustrated below by way of several specific embodiments, it will be appreciated that any one following
The not any type of limitation of the invention further of embodiment.
The preparation of the modified polysulfone film of embodiment 1
（1）Polysulfones 15g, Macrogol 4000 1g, silica 2g, DMF are added in there-necked flask
82g, 1g potassium sorbate are heated to 80 DEG C under stirring, continue stirring and are completely dissolved or are dispersed in solvent to solid
In, obtain the casting solution of homogeneous transparent；
（2）Casting solution is naturally cooled into room temperature；
（3）Utilize the abundant deaeration of vacuum defoaming device；
（4）By casting solution on the glass plate under clean dried and room temperature condition with straight glass bar striking into uniform nothing
The liquid film that defect and thickness are 0.2-0.4mm or so, quickly immerses split-phase film forming in running water by the liquid film；
（5）After after the casting solution on glass plate, film forming solidifies and come off in water, it is cleaned with running water and in distillation
72h is soaked in water to complete the abundant exchange between the solvent in film and water, is produced.
The propane diols of embodiment 2 it is refined
（1）Initial filter, by propane diols crude product through 0.45um membrane filtrations, to remove impurity of the particle diameter in more than 0.45um.
（2）Propane diols crude product and extractant ether after extraction, initial filter are respectively 10 extraction tower I's from theoretical cam curve
Top and bottom enter, atmospheric operation, and temperature is 55 DEG C, and flow velocity is 10kg/h, with third after extractant dichloromethane and initial filter
Glycol crude product quality ratio is 0.2, and tower top obtains extraction phase, and tower reactor obtains molten more than the propane diols of propane diols impurity containing polarized
Liquid, extraction phase enters bottom of the theoretical cam curve for 4 extraction tower II, and operating pressure is normal pressure, and tower top is recycled extractant,
Tower reactor obtains being less than containing polarized the extraction agent solution of propane diols impurity.Each tower total energy consumption is 7.5 kilojoules/hour.
（3）Ultrafiltration, takes raffinate phase, the modified polysulfone film ultrafiltration prepared through embodiment 1.Finished product propane diols is obtained, can be used
In the preparation of injection.
The propane diols of embodiment 3 it is refined
（1）Initial filter, by propane diols crude product through 0.45um membrane filtrations, to remove impurity of the particle diameter in more than 0.45um.
（2）Propane diols crude product and extractant ether after extraction, initial filter are respectively 10 extraction tower I's from theoretical cam curve
Top and bottom enter, atmospheric operation, and temperature is 55 DEG C, and flow velocity is 10kg/h, with the propane diols after extractant toluene and initial filter
Crude product quality ratio is 0.2, and tower top obtains extraction phase, and tower reactor obtains being more than containing polarized the propylene glycol solution of propane diols impurity, extraction
Take and mutually enter bottom of the theoretical cam curve for 4 extraction tower II, operating pressure is normal pressure, and tower top is recycled extractant, tower reactor
Obtain being less than containing polarized the extraction agent solution of propane diols impurity.Each tower total energy consumption is 7.5 kilojoules/hour.
（3）Ultrafiltration, takes raffinate phase, the modified polysulfone film ultrafiltration prepared through embodiment 1.Finished product propane diols is obtained, can be used
In the preparation of injection.
The preparation of the contrast PS membrane of comparative example 1
（1）Polysulfones 15g, Macrogol 4000 1g, silica 2g, DMF are added in there-necked flask
82g, is heated to 80 DEG C under stirring, continue to stir be completely dissolved to solid or it is dispersed in a solvent, obtain
Even transparent casting solution；
（2）Casting solution is naturally cooled into room temperature；
（3）Utilize the abundant deaeration of vacuum defoaming device；
（4）By casting solution on the glass plate under clean dried and room temperature condition with straight glass bar striking into uniform nothing
The liquid film that defect and thickness are 0.2-0.4mm or so, quickly immerses split-phase film forming in running water by the liquid film；
（5）After after the casting solution on glass plate, film forming solidifies and come off in water, it is cleaned with running water and in distillation
72h is soaked in water to complete the abundant exchange between the solvent in film and water, is produced.
The propane diols of comparative example 2 it is refined
Without first filtering technology, other be the same as Examples 2 are operated.
The propane diols of comparative example 3 it is refined
The PS membrane ultrafiltration prepared using comparative example 1, other be the same as Examples 2 are operated.
The preparation method of medical-grade propylene glycol disclosed in the CN101704719B of comparative example 4,
The industrial grade propylene glycols of 1000g are added in 1500ml flask, 15.5g zeolite-chitosan sphere particle is added,
Vibrate 1 minute, adsorb 20 minutes at intervals of two minutes, filtering.5g is added into filtrate（0.5%）Activated carbon, 80 DEG C are incubated 30 minutes；
Then Buchner funnel is used（400 mesh）Filtered；Filtrate is finally heated to 100 DEG C of dehydration by evaporation 30 minutes, product is obtained.
To embodiment 2 and comparative example 2-4 product foundation《Chinese Pharmacopoeia》The four injection propane diols of version in 2015
Standard test, the assay of leading indicator is shown in Table 1.
The calculating of yield：Yield=final product quality/propane diols crude product quality × 100%
The assay summary sheet of the embodiment 2 of table 1 and comparative example 2-4 products
。
Result above shows, with propane diols made from the present invention program, has in the indexs such as impurity, endotoxin and protrudes
Advantage, the auxiliary material for being suitable as injection uses.
Claims (4)
1. a kind of process for purification of propane diols, it is characterised in that comprise the following steps：
(1) initial filter：Impurity by pre-treatment by particle diameter in propane diols crude product in more than 0.45um is removed；(2) extract：Extraction is removed
The less impurity of depolarization, obtains raffinate phase；(3) ultrafiltration：Take raffinate phase, and modified PS membrane ultrafiltration；
Described extraction, comprises the following steps：(1) propane diols crude product and extractant after initial filter are respectively from extraction tower I top
Enter with bottom, tower top obtains extraction phase, tower reactor obtains being more than containing polarized the propylene glycol solution of propane diols impurity, and extraction phase enters
Enter the bottom of extraction tower, tower top is recycled extractant, and tower reactor obtains being less than containing polarized the extraction agent solution of propane diols impurity；
One or more mixing of the extractant in toluene, dichloromethane, chloroform, ether, carbon tetrachloride are molten
Liquid；Propane diols crude product and extractant after initial filter enter from theoretical cam curve for 5-12 extraction towers I top and bottom respectively,
Flow velocity is 10kg/h, and extractant is 0.1-0.4 with the propane diols crude product mass ratio after initial filter, and operating pressure is normal pressure, and temperature is
55 DEG C, tower top obtains extraction phase, and tower reactor obtains being more than containing polarized the propylene glycol solution of propane diols impurity；Extraction phase enters theoretical
Pedal number is 4 extraction tower II bottom, and operating pressure is normal pressure, and tower top is recycled extractant, and tower reactor obtains minimal amount of contain
Polarized is less than the extraction agent solution of propane diols impurity, and each tower total energy consumption is 5-10 kilojoules/hour；
Described modified polysulfone film is using DMF as casting film solvent, according to polysulfones：Macrogol 4000：Two
Silica=15:1：2 mass ratio, the acylate of addition casting solution gross mass 0.1~5%, is prepared into through phase transfer method
Arrive, described acylate is potassium sorbate.
2. according to the method described in claim 1, it is characterised in that described propane diols crude product is selected from industrial grade propylene glycol, food
The mixture of grade propane diols, one kind in medicinal grade propylene glycol or any two or three kinds.
3. according to the method described in claim 1, it is characterised in that described propane diols crude product is expoxy propane direct hydration
Method, expoxy propane indirect hydration method, propylene Direct Catalytic Oxidation method, bioid engineering method, dimethyl carbonate and propane diols co-production method
In a kind of prepare.
4. according to the method described in claim 1, it is characterised in that described DMF is casting solution gross mass
82%.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201610271714.5A CN105924331B (en) | 2016-04-28 | 2016-04-28 | A kind of process for purification of propane diols |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201610271714.5A CN105924331B (en) | 2016-04-28 | 2016-04-28 | A kind of process for purification of propane diols |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN105924331A CN105924331A (en) | 2016-09-07 |
| CN105924331B true CN105924331B (en) | 2017-09-22 |
Family
ID=56836537
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201610271714.5A Active CN105924331B (en) | 2016-04-28 | 2016-04-28 | A kind of process for purification of propane diols |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN105924331B (en) |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101704719B (en) * | 2009-12-08 | 2013-05-01 | 湖南尔康制药股份有限公司 | Method for preparing medical-grade propylene glycol |
| WO2011076690A1 (en) * | 2009-12-22 | 2011-06-30 | Metabolic Explorer | Method for purifying 1,2-propanediol from a fermentation broth |
| US8648219B2 (en) * | 2010-08-20 | 2014-02-11 | James Cramer | Method for purifying glycerin and products obtained therefrom |
| CN102921317A (en) * | 2012-11-19 | 2013-02-13 | 杭州水处理技术研究开发中心有限公司 | Preparation method of polysulfone ultrafiltration membrane |
-
2016
- 2016-04-28 CN CN201610271714.5A patent/CN105924331B/en active Active
Also Published As
| Publication number | Publication date |
|---|---|
| CN105924331A (en) | 2016-09-07 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN103342631B (en) | Process for separating propylene glycol monomethyl ether aqueous solution by using double membrane coupling technology | |
| EP2609989A1 (en) | Method for obtaining lactic acid with a high degree of purity from fermentative liquor | |
| CN102238990A (en) | Method for purifying an alcohol from a fermentation broth using a falling film, a wiped film, a thin film or a short path evaporator | |
| CN106810450A (en) | The apparatus and method that a kind of catalytic reaction rectification prepares dibutyl phthalate | |
| CN109384666A (en) | A method of organic acid in linkage recycling aqueous solutions of organic acids | |
| CN103827072A (en) | Method for recovering acetic acid | |
| CN104109078B (en) | A kind of method that in Sulpyrine production, ethanol reclaims | |
| CN106316832A (en) | Method for obtaining high-purity lactic acid by separating non-calcium salt lactic acid fermentation broth | |
| WO2012088951A1 (en) | Process for recovering vehicle in pharmaceutical industry | |
| CN101182079A (en) | Citric acid mother liquor treatment process | |
| CN107383135A (en) | The method that β thymidines are isolated and purified from zymotic fluid | |
| CN107573248A (en) | The recovery method of resolving agent R phenyl ethylamines in prepared by R-DHLA | |
| CN102977373B (en) | Preparation method of hydroxyfluorosilicone oil | |
| CN103772186B (en) | A kind of process for purification of fermentation organic acid | |
| CN105924331B (en) | A kind of process for purification of propane diols | |
| CN103804173A (en) | Fermentation organic acid refining method | |
| CN102153224A (en) | Treatment technology for industrial sewage from sodium carboxymethylcellulose | |
| CN109422642A (en) | Refining methd, the production method and equipment of pharmaceutical grade sodium benzoate of benzoic acid | |
| CN108424350A (en) | A kind of technique of purification medicinal ethyl alcohol | |
| CN104876817B (en) | A kind of method that use succinic acid fermentation liquor extracts succinic acid | |
| CN104591999A (en) | Long chain organic acid purifying method | |
| CN103804174A (en) | Organic acid refining method | |
| CN114534294B (en) | Energy-saving device and method for separating mixture containing ethylene glycol | |
| CN110372496A (en) | A kind of method of electrodialysis purification neopentyl glycol sodium formate mixed liquor | |
| CN102229521B (en) | Process for refining crude glycerin and recovering byproducts |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant |