CN110255519A - A kind of purification process of pharmaceutical grade phosphoric acid - Google Patents
A kind of purification process of pharmaceutical grade phosphoric acid Download PDFInfo
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- CN110255519A CN110255519A CN201910644158.5A CN201910644158A CN110255519A CN 110255519 A CN110255519 A CN 110255519A CN 201910644158 A CN201910644158 A CN 201910644158A CN 110255519 A CN110255519 A CN 110255519A
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- phosphoric acid
- pharmaceutical grade
- purification process
- crystal
- freezing
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- C—CHEMISTRY; METALLURGY
- C01—INORGANIC CHEMISTRY
- C01B—NON-METALLIC ELEMENTS; COMPOUNDS THEREOF; METALLOIDS OR COMPOUNDS THEREOF NOT COVERED BY SUBCLASS C01C
- C01B25/00—Phosphorus; Compounds thereof
- C01B25/16—Oxyacids of phosphorus; Salts thereof
- C01B25/18—Phosphoric acid
- C01B25/234—Purification; Stabilisation; Concentration
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Abstract
The invention belongs to field of medicaments, and in particular to a kind of purification process of pharmaceutical grade phosphoric acid.The purification process of pharmaceutical grade phosphoric acid provided by the invention prepares crystal seed in such a way that condensing crystallizing and freezing and crystallizing combine, and then frozen cooling, crystallization, are most dehydrated afterwards, are melted.The problems such as the method overcome operating time existing in the prior art is long, energy consumption is high, equipment investment is big, has that equipment investment is few, low energy consumption, easy to operate, the time is few, it is easy to accomplish the advantages that industrialized production.
Description
Technical field
The invention belongs to field of medicaments, and in particular to a kind of purification process of pharmaceutical grade phosphoric acid.
Background technique
Phosphoric acid is also known as orthophosphoric acid (molecular structural formula H3PO4), sterling is colorless transparent viscous liquid or rhomboidal crystal, nothing
It is smelly, taste is very sour.42.35 DEG C of fusing point, specific gravity 1.70, higher boiling acid can be dissolved each other with any ratio with water, be dissolved in ethyl alcohol.85% phosphoric acid
It is colorless and transparent or slightly light thick liquid.
Phosphoric acid is widely used in a variety of pharmaceutical preparations as acidulant and buffer, is widely used as acid in food
Agent, flavouring, collaboration antioxidant (0.001%~0.005%) and chelating agent.In treatment, phosphoric acid,diluted sufficiently dilute after by with
In treatment nausea and vomiting.35% phosphoric acid gel is used to corrode enamel in dentistry.
Often content is relatively low for commercially available PHOSPHORIC ACID TECH.GRADE, and impurity is more, is not able to satisfy the requirement of pharmaceutical grade phosphoric acid, therefore
It needs further to purify it.Method for purifying phosphoric acid is broadly divided into three categories at present: ion-exchange, physical cleaning
Method, chemicalpurification.Wherein content of the purging by crystallization method in physical cleaning method because can disposably reduce various impurity, technique stream
Journey is short, investment cost is lower and operation controls the advantages that of less demanding and is widely used.
The preparing electronic-grade phosphoric acid via melting-crystallization of Chinese patent 200610013611.5, wall built-up produces at -45~-35 DEG C
Raw crystal seed then heats to -2~10 DEG C, and raw material, which is added, in circulation makes it after the crystal that seed surface grows densification, with 2~5 DEG C
Heating rate heating, exclude liquid quality be crystal quality 10~40% when stop, yield is 12~20%.The method operation
Temperature is extremely low, and energy consumption is high, and needs to carry out raw material pretreatment and remove arsenic, and the operating time is long, high production cost, low yield.
The preparing highly-pure phosphoric acid by flow chromatographic crystallization method of Chinese patent 201010100473.0 goes out crystalline substance using additional sound field,
(major impurity ion concentration is respectively less than 1.7mg/L, and micro-pore-film filtration is needed to handle) high to raw materials used purity requirement, application
Difficulty is larger, is not easy to industrialize.
Chinese patent 201010104321.8 prepares electron-level phosphoric acid using liquid membrane crystal method, on 10~20 DEG C of wall surface
Crystal seed is added and starts simultaneously at cooling, keeps wall surface temperature at 5~10 DEG C, the leaching of raw material phosphoric acid liquid is added in by wall surface by distributor
On, epitaxial is grown into wall surface, thickness stops charging when reaching the 1/4~1/3 of tower diameter, constant temperature stands 15~30min, makes not hang
Film phosphoric acid liquid is sufficiently discharged, and terminates after 15~29 DEG C of 0.5~2h of sweating.The method improves crystal seed producing method, by operation temperature
Degree is increased to easy to reach section, but mother liquor removing is not thorough needs and carries out crystallization operation twice, and the operating time is long, and crystallization produces
Rate (20~30%) is not high.
In summary, the generally existing operation temperature of the prior art is too low, and energy consumption is high, is not easy to industrialized production, when operation
Between long, the disadvantages such as crystallization yields are low.
Summary of the invention
In order to overcome disadvantage existing in the prior art, the object of the present invention is to provide a kind of purifying sides of pharmaceutical grade phosphoric acid
Method.The purification process of pharmaceutical grade phosphoric acid provided by the invention, can greatly reduce equipment investment, and low energy consumption, easy to operate, flower
It is time-consuming few, it is easy to accomplish industrialization production, and crystallization yields are higher.
In order to achieve the above object, the technical solution adopted by the present invention are as follows:
A kind of purification process of pharmaceutical grade phosphoric acid, includes the following steps:
S1, crystal seed preparation: by condensing crystallizing and freeze crystallization combine in the way of, be made the good half water phosphorus of crystal form
Acid；
S2, frozen cooling: it goes to take 300~2500mL phosphate raw material, after sand core funnel filters, cool, obtains low temperature
Phosphate raw material；
S3, freezing and crystallizing: it is good that crystal form obtained by 0.6~2g step S1 is added into the phosphate raw material of low temperature obtained by step S2
Half water phosphoric acid, carry out freezing processing, obtain the crystallizing system of freezing；
S4, dehydration: the crystallizing system freezed obtained by step S3 is put into low-temperature cooling fluid circulating pump, is cooled to 14~16
DEG C when, mother liquor is removed in a manner of vacuum filtration, obtains phosphoric acid crystal；
S5, fusing: by phosphoric acid crystal obtained by step S4 carry out water-bath fusing to get.
Preferably, the concrete operations that the condensing crystallizing in the step S1 and freezing and crystallizing combine are as follows: by pharmaceutical grade phosphoric acid
It is dissolved in water, is prepared into 75% phosphoric acid solution, is crystallized under conditions of 20~23 DEG C of temperature, 101kPa, 95% can be obtained
Above crystal handles 1~3h in conjunction with the mode of freezing, is subsequently placed in water-bath and maintains the temperature at 50~60 DEG C, make crystal
It is dissolved into half water state.
Preferably, the concrete operations of the processing that cools in the step S2 are after filtering phosphate raw material, to be added to
Low-temperature cooling fluid circulating pump is cooled to -2~0 DEG C.
Preferably, the freezing processing time in the step S3 is 1~2h.
Preferably, the concrete operations being filtered by vacuum in the step S4 are as follows: the sample that will be filtered is placed in Buchner funnel
It is filtered by vacuum, is dripped to funnel bottom no liquid, stopped filtering, pour out crystal.
Preferably, temperature when water-bath is melted in the step S5 is 40~60 DEG C.
In the present invention, when preparing crystal seed, by condensing crystallizing and freezing and crystallizing combine in the way of handle phosphoric acid
Solution, crystal seed obtained is impure few, removes mother liquor by the way of vacuum filtration, improves while reducing crystallization time
Crystal yield.Moreover, only relating to a kind of low-temperature cooling fluid circulating pump, greatly in the pharmaceutical grade phosphoric acid purification method that this hair provides
Ground reduces purifying cost, reduces energy consumption.
Compared with prior art, the advantages of the purification process of pharmaceutical grade phosphoric acid provided by the invention are as follows:
(1) purification process of pharmaceutical grade phosphoric acid provided by the invention, is removed mother liquor by the way of vacuum filtration, obtained
Crystalline content is high, and crystal yield is 60% or more；
(2) purification process of pharmaceutical grade phosphoric acid provided by the invention, the side combined using condensing crystallizing and freezing and crystallizing
Crystal seed is precipitated in formula, and finally obtained crystal seed is in half water state, helps to improve crystalline content；
(3) purification process of pharmaceutical grade phosphoric acid provided by the invention, instrument is few, invests low, consuming little energy, due to
Operating process is simple, reduces purification time, easily realization industrialization production.
Specific embodiment
The present invention is further explained combined with specific embodiments below, it is noted that following embodiment is only
To explain the present invention, and it cannot be used to limit the present invention, all technical solutions same or similar with the present invention are in this hair
Within bright protection scope.Unless otherwise specified, what technological means used in embodiment was well known to those skilled in the art
Conventional means, raw materials used is commercial goods.
The low-temperature cooling fluid circulating pump is purchased from；The pharmaceutical grade phosphoric acid is purchased from；The Buchner funnel is purchased from.
A kind of purification process of the pharmaceutical grade phosphoric acid of embodiment 1
The purification process of the pharmaceutical grade phosphoric acid, includes the following steps:
S1, crystal seed preparation: being dissolved in water for pharmaceutical grade phosphoric acid, be prepared into 75% phosphoric acid solution, in 20 DEG C of temperature,
It is crystallized under conditions of 101kPa, 95% or more crystal can be obtained, handled 1h in conjunction with the mode of freezing, be subsequently placed in water-bath
In maintain the temperature at 50 DEG C, make dissolution of crystals at half water state, the good half water phosphoric acid of crystal form be made；
S2, frozen cooling: taking the phosphate raw material of 300mL, after sand core funnel filters, cools to -2 DEG C, obtains low temperature
Phosphate raw material；
S3, freezing and crystallizing: it is good that crystal form obtained by 0.6g step S1 is added into the phosphate raw material of low temperature obtained by step S2
Half water phosphoric acid carries out freezing processing 1h, obtains the crystallizing system of freezing；
S4, dehydration: the crystallizing system freezed obtained by step S3 is put into low-temperature cooling fluid circulating pump, is cooled to 16 DEG C
When, it is placed in Buchner funnel and is filtered by vacuum, dripped to funnel bottom no liquid, stop filtering, pour out crystal, obtain phosphorus
Acid crystal；
S5, fusing: by phosphoric acid crystal obtained by step S4 is carried out under conditions of 60 DEG C water-bath melt to get.
A kind of purification process of the pharmaceutical grade phosphoric acid of embodiment 2
The purification process of the pharmaceutical grade phosphoric acid, includes the following steps:
S1, crystal seed preparation: being dissolved in water for pharmaceutical grade phosphoric acid, be prepared into 75% phosphoric acid solution, in 23 DEG C of temperature,
It is crystallized under conditions of 101kPa, 95% or more crystal can be obtained, handled 3h in conjunction with the mode of freezing, be subsequently placed in water-bath
In maintain the temperature at 60 DEG C, make dissolution of crystals at half water state, the good half water phosphoric acid of crystal form be made；
S2, frozen cooling: taking the phosphate raw material of 800mL, after sand core funnel filters, cools to -1 DEG C, obtains low temperature
Phosphate raw material；
S3, freezing and crystallizing: it is good that crystal form obtained by 1.5g step S1 is added into the phosphate raw material of low temperature obtained by step S2
Half water phosphoric acid carries out freezing processing 2h, obtains the crystallizing system of freezing；
S4, dehydration: the crystallizing system freezed obtained by step S3 is put into low-temperature cooling fluid circulating pump, is cooled to 15 DEG C
When, it is placed in Buchner funnel and is filtered by vacuum, dripped to funnel bottom no liquid, stop filtering, pour out crystal, obtain phosphorus
Acid crystal；
S5, fusing: by phosphoric acid crystal obtained by step S4 is carried out under conditions of 55 DEG C water-bath melt to get.
A kind of purification process of the pharmaceutical grade phosphoric acid of embodiment 3
The purification process of the pharmaceutical grade phosphoric acid, includes the following steps:
S1, crystal seed preparation: being dissolved in water for pharmaceutical grade phosphoric acid, be prepared into 75% phosphoric acid solution, in 22 DEG C of temperature,
It is crystallized under conditions of 101kPa, 95% or more crystal can be obtained, handled 2h in conjunction with the mode of freezing, be subsequently placed in water-bath
In maintain the temperature at 55 DEG C, make dissolution of crystals at half water state, the good half water phosphoric acid of crystal form be made；
S2, frozen cooling: taking the phosphate raw material of 2500mL, after sand core funnel filters, cools to 0 DEG C, obtains low temperature
Phosphate raw material；
S3, freezing and crystallizing: crystal form obtained by 2g step S1 good half is added into the phosphate raw material of low temperature obtained by step S2
Water phosphoric acid carries out freezing processing 1.5h, obtains the crystallizing system of freezing；
S4, dehydration: the crystallizing system freezed obtained by step S3 is put into low-temperature cooling fluid circulating pump, is cooled to 14 DEG C
When, it is placed in Buchner funnel and is filtered by vacuum, dripped to funnel bottom no liquid, stop filtering, pour out crystal, obtain phosphorus
Acid crystal；
S5, fusing: by phosphoric acid crystal obtained by step S4 is carried out under conditions of 45 DEG C water-bath melt to get.
A kind of purification process of the pharmaceutical grade phosphoric acid of comparative example 1
The purification process of the pharmaceutical grade phosphoric acid is similar to Example 3；
Difference with embodiment 3 is that the purification process of pharmaceutical grade phosphoric acid is adopted in the crystal seed preparation of step S1 in comparative example 1
It is precipitated with the mode of condensing crystallizing.
A kind of purification process of the pharmaceutical grade phosphoric acid of comparative example 2
The purification process of the pharmaceutical grade phosphoric acid is similar to Example 3；
Difference with embodiment 3 is that the purification process of pharmaceutical grade phosphoric acid is filtered in step s 4 in comparative example 2
When, it is directly filtered with Buchner funnel, without being vacuum-treated.
The comparison of test example purification efficiency
1. test specimen: phosphorus made from the purification process using pharmaceutical grade phosphoric acid described in embodiment 1-3 and comparative example 1-2
Acid；
2. test method: using the standard of phosphoric acid in 2015 version " Chinese Pharmacopoeia " as foundation, detecting the content and receipts of phosphoric acid
Rate；
3. test result: specific test result is shown in Table 1.
Table 1 after purification phosphoric acid index of correlation comparison
As shown in Table 1, the phosphoric acid purified using method described in 1-3 of the embodiment of the present invention, content 87% or more,
And phosphoric acid crystal recovery rate is 60% or more, and in comparative example 1-2, due to changing some purification conditions, final gained phosphoric acid
Content reduces, especially 2 groups of comparative example, eliminates vacuum condition, phosphorus acid content and yield significantly reduce.
Finally it should be noted that the above embodiments are merely illustrative of the technical solutions of the present invention rather than protects to the present invention
The limitation of range, although elaborating referring to preferred embodiment to the present invention, those skilled in the art should be managed
Solution, can with modification or equivalent replacement of the technical solution of the present invention are made, without departing from technical solution of the present invention essence and
Range.
Claims (6)
1. a kind of purification process of pharmaceutical grade phosphoric acid, which is characterized in that operating procedure is as follows:
S1, crystal seed preparation: by condensing crystallizing and freeze crystallization combine in the way of, be made the good half water phosphoric acid of crystal form；
S2, frozen cooling: taking the phosphate raw material of 300~2500mL, after sand core funnel filters, cool, and obtains the phosphorus of low temperature
Acid starting material；
S3, freezing and crystallizing: crystal form obtained by 0.6~2g step S1 good half is added into the phosphate raw material of low temperature obtained by step S2
Water phosphoric acid carries out freezing processing, obtains the crystallizing system of freezing；
S4, dehydration: the crystallizing system freezed obtained by step S3 is put into low-temperature cooling fluid circulating pump, is cooled to 14~16 DEG C
When, mother liquor is removed in a manner of vacuum filtration, obtains phosphoric acid crystal；
S5, fusing: by phosphoric acid crystal obtained by step S4 carry out water-bath fusing to get.
2. the purification process of pharmaceutical grade phosphoric acid as described in claim 1, which is characterized in that condensing crystallizing in the step S1 with
The concrete operations that freezing and crystallizing combines are as follows: pharmaceutical grade phosphoric acid is dissolved in water, is prepared into 75% phosphoric acid solution, at 20~23 DEG C
Temperature, crystallize under conditions of 101kPa, 95% or more crystal can be obtained, handle 1~3h in conjunction with the mode of freezing, so
It is placed in water-bath and maintains the temperature at 50~60 DEG C, make dissolution of crystals at half water state.
3. the purification process of pharmaceutical grade phosphoric acid as described in claim 1, which is characterized in that the place that cools in the step S2
The concrete operations of reason are after filtering phosphate raw material, to be added to low-temperature cooling fluid circulating pump, be cooled to -2~0 DEG C.
4. the purification process of pharmaceutical grade phosphoric acid as described in claim 1, which is characterized in that when freezing processing in the step S3
Between be 1~2h.
5. the purification process of pharmaceutical grade phosphoric acid as described in claim 1, which is characterized in that the tool being filtered by vacuum in the step S4
Gymnastics as: the sample that will be filtered, which is placed in Buchner funnel, to be filtered by vacuum, to funnel bottom no liquid drip, stop take out
Filter, pours out crystal.
6. the purification process of pharmaceutical grade phosphoric acid as described in claim 1, which is characterized in that when water-bath is melted in the step S5
Temperature is 40~60 DEG C.
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Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4657559A (en) * | 1985-05-08 | 1987-04-14 | Freeport Research And Engineering Company | Process for seed crystal preparation for phosphoric acid crystallization |
| CN102583283A (en) * | 2012-01-13 | 2012-07-18 | 四川大学 | Method for preparing electronic-grade phosphoric acid via melting-crystallization |
| CN104030261A (en) * | 2013-12-30 | 2014-09-10 | 广西明利化工有限公司 | A production method of high-purity electronic grade phosphoric acid |
-
2019
- 2019-07-17 CN CN201910644158.5A patent/CN110255519A/en active Pending
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4657559A (en) * | 1985-05-08 | 1987-04-14 | Freeport Research And Engineering Company | Process for seed crystal preparation for phosphoric acid crystallization |
| CN102583283A (en) * | 2012-01-13 | 2012-07-18 | 四川大学 | Method for preparing electronic-grade phosphoric acid via melting-crystallization |
| CN104030261A (en) * | 2013-12-30 | 2014-09-10 | 广西明利化工有限公司 | A production method of high-purity electronic grade phosphoric acid |
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Application publication date: 20190920 |
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