CN111035963A

CN111035963A - Method for decoloring vitamin B6 and device for decoloring vitamin B6

Info

Publication number: CN111035963A
Application number: CN201911422112.5A
Authority: CN
Inventors: 李连中; 徐光明; 鲁向阳
Original assignee: Shanghai Acebright Pharmaceuticals Group Co ltd; Chifeng Pharmaceutical Co ltd
Current assignee: Shanghai Acebright Pharmaceuticals Group Co ltd; Chifeng Pharmaceutical Co ltd
Priority date: 2019-12-31
Filing date: 2019-12-31
Publication date: 2020-04-21
Anticipated expiration: 2039-12-31
Also published as: CN111035963B

Abstract

The invention provides a method for decoloring vitamin B6 and a device for decoloring vitamin B6. Specifically, the method comprises the steps of: feeding the crude vitamin B6 solution into a decoloring column group formed by connecting n decoloring columns in series, and decoloring; detecting the transmittance of filtrate at a discharge port of the decoloring column group, and stopping feeding when the transmittance of the filtrate is lower than a threshold value; separating the decolorizing column (namely a feeding column) closest to the feeding hole from the decolorizing column group, and connecting a new decolorizing column in series at the discharging hole of the nth decolorizing column, wherein the new decolorizing column is filled with granular activated carbon; feeding the crude vitamin B6 solution through the feed inlet of the decoloring column group obtained in the step (4), and continuously decoloring; until the decolorization of the crude vitamin B6 solution is completed. The method has the advantages of low consumption of active carbon, high decolorization efficiency and good decolorization effect.

Description

Method for decoloring vitamin B6 and device for decoloring vitamin B6

Technical Field

The invention relates to the field of chemical industry, in particular to a method for decoloring vitamin B6 and a device for decoloring vitamin B6.

Background

Vitamin B6 is also known as pyridoxine, a water-soluble vitamin. Vitamin B6 has important effects in preventing or treating vitamin B6 deficiency, preventing and treating isoniazid poisoning, treating infantile convulsion, and reducing leukopenia. In addition, vitamin B6 is an important coenzyme for poultry, and poultry cannot synthesize vitamin B6 and must take the vitamin B from feed. At present, the production method of vitamin B6 which is widely applied industrially is an oxazole method, but the product obtained by the method has darker color, and impurities are difficult to remove because the impurities are closer to the physicochemical property of vitamin B6. Therefore, researchers have conducted many researches on the process of vitamin B6, and the decolorization and recrystallization of activated carbon are the most widely used in industry.

Weekly Yuan et al (journal of Chinese medical industry, 1994, (09):385-389) adopts the following method to decolorize: dissolving 18.5g of vitamin B6 crude product in 100ml of water, adding 1.7g of activated carbon, decoloring at 80 ℃ for 30min, filtering, adding 1.7g of activated carbon, and decoloring at 80 ℃ for 30 min. Filtering, concentrating the filtrate to dryness, and adding ethanol for crystallization to obtain fine VB 6. The method needs two kettle-type decolorizations, is complex to operate, has the total consumption of the active carbon about 18 percent of the crude product of the vitamin B6, and has large consumption of the active carbon and high production cost.

Chentianhao et al (journal of Chinese medicine industry, 2004,35 (1): 1-2) decolorize at 80 deg.C for 30min each time in a kettle type 3 times, the consumption of active carbon is 16% of the crude product. The method has the following defects: kettle type decolorization is carried out for 3 times, the operation is complicated, the total dosage of the active carbon is 16 percent of the crude product of the vitamin B6, and the dosage of the active carbon is large.

CN202951403 uses conventional kettle type activated carbon to decolorize vitamin B6, and then removes impurities by ultrafiltration.

In the decoloring process, the large amount of the activated carbon (which exceeds 15 percent of the weight of the product to be decolored) is used, so that a large amount of activated carbon solid waste is generated in the production process, and huge solid waste treatment pressure and higher production cost are brought. In addition, in the actual industrial production, batch operation is required, the operation process is complicated, the contact time of the activated carbon and the vitamin B6 is prolonged, the deterioration amount of the vitamin B6 in the decoloring process is increased, and the yield is reduced.

Therefore, a method for decoloring vitamin B6, which has the advantages of low consumption of activated carbon, high decoloring efficiency and good decoloring effect, is urgently needed in the field.

Disclosure of Invention

The invention aims to provide a vitamin B6 decoloring method which has the advantages of less consumption of activated carbon, high decoloring efficiency and good decoloring effect.

In a first aspect of the present invention, there is provided a method for decoloring vitamin B6, comprising the steps of:

(1) providing a vitamin B6 crude product solution and a decolorizing column group, wherein the decolorizing column group is formed by connecting n decolorizing columns in series, and n is an integer more than or equal to 2; the decolorizing column is a hollow tubular column, the top of the decolorizing column is provided with a feed inlet, the bottom of the decolorizing column is provided with a discharge outlet, and the lower end of the inner wall of the decolorizing column is provided with a liquid-permeable baffle; the feed inlet of the 1 st decolorizing column (namely the feed column) forms the feed inlet of the decolorizing column group; the discharge hole of the nth decolorizing column (namely the discharge column) forms the discharge hole of the decolorizing column group; wherein, granular active carbon is filled in each decolorizing column;

(2) feeding the crude vitamin B6 solution into the decoloring column group through the feed inlet, and decoloring;

(3) detecting the transmittance of filtrate at a discharge port of the decoloring column group, and stopping feeding when the transmittance of the filtrate is lower than a threshold value;

(4) separating the decolorizing column (namely a feeding column) closest to the feeding hole from the decolorizing column group, and connecting a new decolorizing column in series at the discharging hole of the nth decolorizing column, wherein the new decolorizing column is filled with granular activated carbon; and

(5) feeding the crude vitamin B6 solution through the feed inlet of the decoloring column group obtained in the step (4), and continuously decoloring;

(6) and (5) repeating the steps (3) to (5) until the decolorization of the crude vitamin B6 solution is completed.

In another preferred embodiment, the granular activated carbon has the following characteristics:

(a) the iodine value of the granular activated carbon is 1000-1200 mg/g;

(b) the mesh number of the granular active carbon is 10-80 meshes;

(c) the mechanical strength of the granular activated carbon is 40-80%; and

(d) the caramel decolorization rate of the granular activated carbon is more than or equal to 95 percent.

In another preferred embodiment, the crude vitamin B6 solution has one or more characteristics selected from the group consisting of:

1) the vitamin B6 crude product is prepared by an oxazole method;

2) the solvent of the crude vitamin B6 solution is water or an aqueous solvent;

3) the light transmittance of the vitamin B6 crude product solution is 0-0.8, preferably less than or equal to 0.6, less than or equal to 0.5, less than or equal to 0.4, less than or equal to 0.3, less than or equal to 0.2, less than or equal to 0.1 or less than or equal to 0.02;

4) the concentration of the vitamin B6 in the vitamin B6 crude product solution is 0.001-0.5g/mL, preferably 0.01-0.4g/mL, preferably 0.05-0.3 g/mL; and/or

5) The crude vitamin B6 solution is an unsaturated solution at the decolorizing temperature.

In another preferred embodiment, the transmittance of the solution of the crude vitamin B6 is 0.5-0.8, preferably 0.6-0.8, more preferably 0.7-0.8.

In another preferred example, the decolorizing column comprises a supporting layer and an activated carbon layer which are sequentially filled from bottom to top.

In another preferred embodiment, the filler of the support layer is selected from the group consisting of: glass beads, polymeric microspheres, or a combination thereof.

In another preferred embodiment, the filler of the support layer has an average diameter of 0.5 to 5mm, preferably 1 to 3 mm.

In another preferred example, the liquid-permeable barrier is a barrier having a through hole or a passage through which liquid can pass.

In another preferred example, a filter layer is further included below the support layer and/or the activated carbon layer.

In another preferred embodiment, the thickness of the support layer is 1-10cm, preferably 2-10 cm.

In another preferred embodiment, the decolorizing column further comprises one or more of the following features:

1) the decolorizing column also comprises a jacket, the jacket surrounds the decolorizing column, and the jacket comprises a water inlet and a water outlet and is used for heating and/or insulating the decolorizing column in a water bath;

2) the decolorizing column also comprises a temperature sensor arranged at the upper end of the decolorizing column, and the temperature sensor is used for detecting the temperature in the decolorizing column; and/or

3) And a valve is arranged between the decoloring column liquid-permeable baffle and the discharge hole.

In another preferred embodiment, the decolorizing column set further comprises one or more of the following features:

1) the feed inlet of decoloration post group still is connected with continuous feed arrangement, continuous feed arrangement includes: the device comprises a containing container, a peristaltic pump and a feeding hose, wherein the feeding hose is connected with the container and a feeding hole of the decolorizing column group;

2) a discharge port of the decoloring column group is provided with a transmittance detection device for detecting the transmittance of filtrate at the discharge port; and/or

3) And a discharge port of the decoloring column group is also provided with a discharge collecting container.

In another preferred embodiment, the container is provided with a heating module.

In another preferred embodiment, the granular activated carbon has one or more of the following characteristics:

1) the iodine value of the granular activated carbon is 1020-1150mg/g, preferably 1050-1120mg/g, and more preferably 1080-1100 mg/g;

2) the mesh number of the granular activated carbon is 20-60 meshes, and preferably, 20-40 meshes or 30-50 meshes;

3) the mechanical strength of the granular activated carbon is 45-75%, more preferably 50-70%; and/or

4) The caramel decolorization rate of the granular activated carbon is more than or equal to 96 percent, more than or equal to 97 percent, more than or equal to 98 percent or more than or equal to 99 percent.

In another preferred embodiment, the step (2) has one or more of the following features:

1) the feeding is batch feeding or continuous feeding;

2) the feeding speed of the vitamin B6 crude product solution is 1-5cm of column height/min, preferably 2-3cm of column height/min;

3) the feeding temperature of the vitamin B6 crude product solution is 10-100 ℃, preferably 50-90 ℃, more preferably 60-85 ℃, and most preferably 75-85 ℃; and/or

4) Setting the temperature of the decolorization at 10-100 ℃, preferably, 50-90 ℃, more preferably, 60-85 ℃, and most preferably, 75-85 ℃;

5) the maximum difference between the feeding temperature of the vitamin B6 crude product solution and the decoloring temperature of each decoloring column is not more than 10 ℃, preferably not more than 5 ℃, and more preferably not more than 4 ℃.

In another preferred embodiment, the weight ratio of the granular activated carbon to the crude vitamin B6 is 1-10:100, preferably 1.2-5:100, and more preferably 1.5-5: 100.

In another preferred embodiment, the total filling height of the granular activated carbon of the n decolorizing columns is 100-.

In another preferred embodiment, the retention time of the vitamin B6 in the decolorizing column set is 20-120min, preferably 30-90min, more preferably 30-80 min.

In another preferred embodiment, n is an integer of 2 to 10, preferably 3 to 6, more preferably 4 to 5.

In another preferred embodiment, the threshold value is 0.70-0.80, preferably 0.72-0.75.

In another preferred example, the method further comprises the steps of:

a) calcining the decolored granular activated carbon generated in the step 4) to obtain regenerated granular activated carbon;

b) the regenerated granular activated carbon is used for packing a decolorizing column.

In another preferred example, when the first-used granular activated carbon is used in combination with the regenerated activated carbon in the decolorizing column set, the first-used granular activated carbon accounts for more than 30%, more than 40%, more than 50%, more than 60%, more than 70%, more than 80%, more than 90%, or 100% of the total amount of activated carbon in the current decolorizing column set.

In another preferred example, the granular activated carbon is regenerated granular activated carbon produced after calcining the decolorized granular activated carbon produced in step 4).

In another preferred embodiment, the decolorizing column contains clean granular activated carbon before decolorizing the crude vitamin B6 solution.

In another preferred embodiment, the "clean granular activated carbon" refers to granular activated carbon which is not adsorbed with impurities (especially colored impurities) in the crude vitamin B6, and can be first-used granular activated carbon, regenerated granular activated carbon (i.e., after decolorizing the crude vitamin B6, performing a regeneration treatment (e.g., calcining to remove organic impurities)), or a combination thereof.

In another preferred example, the method further comprises the steps of: the decolorizing column was washed with water until no powdered charcoal was used.

In another preferred embodiment, the temperature of the water used for washing is not more than 10 ℃, preferably not more than 5 ℃, more preferably not more than 4 ℃ at the maximum difference from the temperature of each bleaching column.

In another preferred embodiment, the method further includes the steps of:

a) washing the decoloration column separated from the step 4) with water, and using the water after washing for preparing a crude vitamin B6 solution.

In a second aspect of the present invention, there is provided a device for decoloring vitamin B6 crude products, the device comprising:

the decoloring column group is formed by connecting n decoloring columns in series; wherein n is an integer not less than 2;

the decolorizing column is a hollow tubular column, the top of the decolorizing column is provided with a feed inlet, the bottom of the decolorizing column is provided with a discharge outlet, and the lower end of the inner wall of the decolorizing column is provided with a liquid-permeable baffle;

the feed inlet of the 1 st decolorizing column (feeding column) forms the feed inlet of the decolorizing column group; the discharge hole of the nth decolorizing column (discharging column) forms the discharge hole of the decolorizing column group; wherein each decolorizing column is filled with granular activated carbon, and the granular activated carbon has the following characteristics:

(a) the iodine value of the granular activated carbon is 1000-1200 mg/g;

(b) the mesh number of the granular active carbon is 10-80 meshes;

(c) the mechanical strength of the granular activated carbon is 40-80%; and

In another preferred example, the liquid-permeable barrier is a barrier having a passage with a through hole through which liquid can pass.

In another preferred embodiment, the decolorizing column has been washed with water to no powdered charcoal.

In another preferred example, the discharge port of the decolorizing column group is also provided with a discharge collecting container.

In another preferred embodiment, the height of the decolorizing column is 10-100cm, preferably 15-80cm, more preferably 20-60 cm.

In another preferred embodiment, the internal diameter of the decolorizing column is 1-20cm, preferably 1.5-10cm, more preferably 2-8 cm.

It is to be understood that within the scope of the present invention, the above-described features of the present invention and those specifically described below (e.g., in the examples) may be combined with each other to form new or preferred embodiments. Not to be reiterated herein, but to the extent of space.

Drawings

FIG. 1 is a schematic diagram of a multi-column tandem configuration according to an embodiment of the present invention.

The reference signs are: 1-container (such as feeding bottle), 2-decolorizing column, 3-discharging collecting container (such as receiving bottle), 4-feeding hole and 5-discharging hole.

Detailed Description

The present inventors have conducted extensive and intensive studies and, as a result, have provided a method and an apparatus for decoloring vitamin B6 through extensive screening and testing. The method adopts the granular activated carbon with specific specification, continuously decolors the crude vitamin B6 product through the serially connected decoloration column group filled with the granular activated carbon, and updates the decoloration columns in a sequential replacement mode, so that the used activated carbon can reach adsorption saturation in the decoloration process, the utilization degree of the activated carbon is exerted to the maximum extent, and the method has the advantages of very low consumption of the activated carbon, less waste and good decoloration effect. The invention also provides a corresponding decoloring device. The present invention has been completed based on this finding.

Term(s) for

Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs.

As used herein, the term "about" when used in reference to a specifically recited value means that the value may vary by no more than 1% from the recited value. For example, as used herein, the expression "about 100" includes 99 and 101 and all values in between (e.g., 99.1, 99.2, 99.3, 99.4, etc.).

As used herein, the term "comprising" or "includes" can be open, semi-closed, and closed. In other words, the term also includes "consisting essentially of …," or "consisting of ….

Vitamin B6 crude product

In the invention, the crude vitamin B6 product refers to vitamin B6 prepared by an oxazole method.

The oxazole method is a commonly used method in the art for synthesizing vitamin B6; the main process comprises three procedures: preparing N-ethoxy oxalyl alanine ethyl ester through esterification reaction; preparing 4-methyl-5-ethoxy oxazole through cyclization reaction; and preparing a crude vitamin B6 product. The preparation process of the method generates a large amount of organic pigments, so that the color of the product is deepened, and the obtained crude vitamin B6 must be refined.

In the decoloring method of the present invention, the crude vitamin B6 is usually decolored in the form of a crude vitamin B6 solution.

In another preferred embodiment, the crude vitamin B6 solution has one or more of the following characteristics:

the solvent of the crude vitamin B6 solution is water or an aqueous solvent;

the transmittance of the vitamin B6 crude product solution is 0-0.8, preferably less than or equal to 0.6, less than or equal to 0.5, less than or equal to 0.4, less than or equal to 0.3, less than or equal to 0.2, less than or equal to 0.1 or less than or equal to 0.02;

the concentration of the vitamin B6 in the vitamin B6 crude product solution is 0.001-0.5g/mL, preferably 0.01-0.4g/mL, preferably 0.05-0.3 g/mL; and/or

The crude vitamin B6 solution is an unsaturated solution at the decolorizing temperature.

In particular, in the present invention, the crude vitamin B6 can be a solution with higher transmittance after being subjected to preliminary decolorization, such as a solution of crude vitamin B6 with transmittance of 0.5-0.8, preferably 0.6-0.8, and more preferably 0.7-0.8.

Granular activated carbon

Activated carbon is a porous adsorbent, and is generally classified into powdered activated carbon and granular activated carbon according to the external shape. In the invention, the granular activated carbon is selected as a decoloring agent because the powdered activated carbon has the problems of easy blockage of a filter surface, difficult separation of powder and the like.

In the present invention, the origin of the granular activated carbon is not particularly required, and includes (but is not limited to): coal, husk, coconut shell, wood, or combinations thereof. The particulate activated carbon of the present invention may be shaped (e.g., columnar) and/or amorphous. In the present invention, representative granular activated carbons include (but are not limited to): wood granular activated carbon, coal granular activated carbon, shell granular activated carbon, coconut shell granular activated carbon, or a combination thereof.

Typically, the mesh size of the granular activated carbon is 10-80 mesh, preferably 20-60 mesh, more preferably 20-40 mesh or 30-50 mesh.

Preferably, the granular activated carbon has a specific iodine value and caramel decolorization rate, wherein when the iodine value is in the range of 1000-1200mg/g and the caramel decolorization rate is in the range of 95-100%, the crude vitamin B6 of the invention is very beneficial to decolorize. When the specific iodine value of the granular activated carbon is not in the range and/or the caramel decolorization ratio is not in the range, the decolorization effect on the crude vitamin B6 of the present invention is significantly reduced.

Generally, coconut shell charcoal and coal charcoal have higher iodine value, and more preferably, coconut shell.

In another preferred embodiment, the iodine value of the granular activated carbon is 1000-1200mg/g, preferably 1020-1150mg/g, preferably 1050-1120mg/g, more preferably 1080-1100 mg/g.

In another preferred example, the caramel decolorization ratio of the granular activated carbon is more than or equal to 95 percent or higher, such as more than or equal to 96 percent, more than or equal to 97 percent, more than or equal to 98 percent, more than or equal to 99 percent or 100 percent

Furthermore, the present inventors have found that when conventionally preferred activated carbon having high mechanical strength (e.g.. gtoreq.85%) is used, the decolorization effect of the crude vitamin B6 is not satisfactory, and thus the amount of activated carbon used is high. Unexpectedly, satisfactory decolorization can be achieved when a specific mechanical strength (40 to 80%) is used.

In the present invention, when the mechanical strength of the granular activated carbon is in the above range (i.e., 40 to 80%), the granular activated carbon is not easily crushed or abraded, thereby greatly reducing or eliminating the crushed carbon that may be present in the filtrate. In the present invention, the mechanical strength of the granular activated carbon is preferably 45 to 75%, more preferably 50 to 70%.

As used herein, the terms "first-use granular activated carbon", "fresh granular activated carbon" are used interchangeably to refer to particulate activated carbon that has never been used.

As used herein, the term "regenerated granular activated carbon" refers to regenerated granular activated carbon after organic impurities have been removed by calcination after the first-use granular activated carbon has been used for decolorization. Methods for regenerating the particulate activated carbon by calcination are known in the art. The regeneration and use times of the regenerated granular activated carbon can be determined by whether the regenerated properties (such as iodine value) meet requirements, and preferably, the regeneration and use times of the regenerated granular activated carbon are 1-2 times.

As used herein, the term "decolorized granular activated carbon" refers to granular activated carbon that adsorbs colored impurities, and may be saturated adsorption or unsaturated adsorption.

The "clean granular activated carbon" refers to granular activated carbon which is not adsorbed with impurities (especially colored impurities) in the crude vitamin B6, and can be firstly used granular activated carbon, regenerated granular activated carbon (used for removing organic impurities through calcination after the crude vitamin B6 is decolored), or a combination thereof.

Decolorizing column

In the invention, the decolorizing column is a hollow column, the top of the column is provided with a feed inlet, the bottom of the column is provided with a discharge outlet, and the lower end of the inner wall of the decolorizing column is provided with a liquid-permeable baffle.

The liquid-permeable baffle can be a perforated baffle arranged parallel to the plane of the feed inlet. Preferably integrally formed with the decolorizing column. In another preferred example, the liquid-permeable barrier is a barrier having a through hole or a passage through which liquid can pass.

And a supporting layer and an activated carbon layer which are sequentially filled from bottom to top are arranged above the liquid-permeable baffle. The support layer is used for supporting the activated carbon, and allowing liquid to pass through to trap the granular activated carbon. In the present invention, the support layer is not particularly required, and one or more support layer fillers commonly used in the art, for example, glass beads, polymeric microspheres, or a combination thereof, may be used. The grain diameter of the filler of the supporting layer can be selected according to the sizes of the liquid-permeable baffle and the active carbon.

The decolorizing column also comprises a jacket surrounding the decolorizing column, wherein the jacket comprises a water inlet and a water outlet and is used for heating in a water bath and/or insulating the decolorizing column. One embodiment of the jacket is referred to as a reflux condenser.

The upper end of the decoloring column can be provided with a temperature sensor for detecting the temperature in the decoloring column. Typically a temperature measured around 1cm above the activated carbon surface.

Preferably, a valve is further arranged between the liquid-permeable baffle of the decolorizing column and the discharge hole. The valve can be opened and closed or the liquid outlet speed of the discharge hole can be adjusted.

The decolorizing column comprises a supporting layer and an active carbon layer which are sequentially filled from bottom to top.

In the present invention, the decolorizing column packed with cleaned granular activated carbon is referred to as a "fresh decolorizing column".

Decoloration device

The present invention provides a decoloring apparatus, the apparatus comprising:

the decoloring column group is formed by connecting n decoloring columns in series;

(a) the iodine value of the granular activated carbon is 1000-1200 mg/g;

(b) the mesh number of the granular active carbon is 10-80 meshes;

(c) the mechanical strength of the granular activated carbon is 40-80%; and

In the decolorizing column set, each decolorizing column optionally has the features described herein for a single decolorizing column, which may be the same or different.

More preferably, in the decolorizing column set of the present invention, the granular activated carbon used is a combination of first-used granular activated carbon and regenerated granular activated carbon. For example, the two are mixed and used for filling, the two are respectively used for filling different decolorizing columns, or the two are filled in the same decolorizing column in a layered mode.

In another preferred example, when the first-used granular activated carbon is used in combination with the regenerated activated carbon in the decolorizing column group, the first-used granular activated carbon accounts for more than 30%, more than 40%, more than 50%, more than 60%, more than 70%, more than 80%, more than 90% of the total amount of the activated carbon in the current decolorizing column group.

In the invention, the term "serially connected" means that the destaining solution comes out from the discharge port of the former destaining column and then enters the feed port of the latter destaining column. In other words, in the present invention, the crude solution must pass through all of the decolorizing columns between its feed and discharge columns. The liquid can be transferred between the decolorizing columns by means of gravity by placing the decolorizing columns one above the other. Or conveyed by a pump (such as a peristaltic pump) and a connecting pipe, wherein the connecting pipe is connected with the discharge hole of the previous decolorizing column and the feed hole of the next decolorizing column.

In another preferred embodiment, the container has a heating module.

In the multi-column tandem decolorization device of the present invention, a peristaltic pump is usually provided at the feed port, and the feed is carried out by the peristaltic pump. In addition, the two adjacent decolorizing columns are connected through a sealing sleeve or a rubber tube and a single-pass joint. For example, the lower end of the decoloring column 1 is connected to the upper end of the decoloring column 2.

Decoloring method

The invention provides a method for decoloring vitamin B6, which comprises the following steps:

(a) the iodine value of the granular activated carbon is 1000-1200 mg/g;

(b) the mesh number of the granular active carbon is 10-80 meshes;

(c) the mechanical strength of the granular activated carbon is 40-80%; and

1) the feeding is batch feeding or continuous feeding;

In another preferred embodiment, the method further includes the steps of:

The term "decoloring temperature" refers to the temperature in the decoloring column at the time of decoloring. Generally, the column internal temperature of each decolorizing column is set to the same temperature. However, it will be understood by those skilled in the art that there may be slight and acceptable temperature differences within the columns, such as maximum differences between the decolorizing temperatures of the individual decolorizing columns of not more than 10 ℃ (i.e. + -. 10 ℃), preferably not more than 5 ℃, more preferably not more than 4 ℃, as long as the temperature difference does not significantly affect the decolorizing effect of vitamin B.

The main advantages of the invention include:

1. the invention provides a vitamin B6 decoloring method, which comprises the steps of continuously decoloring a vitamin B6 crude product by a series decoloring column group filled with activated carbon, and updating decoloring columns in a sequential replacement mode, so that the activated carbon can reach adsorption saturation in the decoloring process, the utilization degree of the activated carbon is exerted to the maximum extent, and the using amount of the activated carbon is greatly reduced.

2. The better the decolorizing effect is when using granular activated carbon of specific specifications (with specific iodine value, caramel decolorizing rate and/or mechanical strength).

3. The inventor also finds that the granular activated carbon still has a good decoloring effect after being used for decoloring a crude vitamin B6 product and removing adsorbed organic impurities by calcining, can be used for refilling a decoloring column, can further reduce the using amount of the activated carbon and generates less solid waste.

4. The decoloring method has the advantages of low cost, high yield, high product purity and environmental friendliness.

5. The invention further provides a device for decoloring, which is simple to operate, can be flexibly assembled and disassembled according to requirements and is convenient to use.

The invention is further illustrated with reference to specific embodiments. It should be understood that these examples are for illustrative purposes only and are not intended to limit the scope of the present invention. The experimental procedures, in which specific conditions are not noted in the following examples, are generally carried out under conventional conditions or conditions recommended by the manufacturers. Unless otherwise indicated, percentages and parts are by weight.

General methods and materials

The method for measuring the transmittance comprises the following steps: 721S type ultraviolet-visible spectrophotometer with cuvette of 1cm, wavelength of 420nm, and distilled water as reference. The lighter the color, the greater the transmittance; the darker the color, the smaller the transmittance (transmittance range 0-1). As the decolorization progresses, the color of the receiving solution gradually deepens and the transmittance gradually decreases. When the decolorization is finished, collecting all decolorized liquid in the decolorization, sampling and measuring the transmittance, namely the transmittance of the decolorized liquid in the decolorization.

Determination of adsorption saturation: when the light transmittance of the decolorized solution from the outlet of a certain decolorization column is reduced to the light transmittance of the crude solution (about 0.012), the activated carbon in the decolorization column is considered to reach adsorption saturation.

The method for calculating the yield of the finished vitamin B6 product comprises the following steps: taking a decolorized solution corresponding to a certain mass (for example, 250g) of a vitamin B6 crude product, performing post-treatment according to the method of the following example 4, and calculating the mass percentage of the obtained finished vitamin B6 product in the crude product, namely the yield.

In the invention, the "amount of activated carbon" or "amount of activated carbon" refers to the mass percentage of the activated carbon used in the decolorization process in the crude decolorized vitamin B6 product. "(activated carbon) total carbon consumption" refers to the mass of activated carbon actually used in the decolorization process.

The test materials and reagents used in the following examples are commercially available without specific reference.

Granular activated carbon: the active carbon used in the examples is purchased from commercially available granular carbon with different specifications, including medicinal granular carbon, industrial granular carbon and special granular carbon for sugar decolorization, and the iodine adsorption value is determined by referring to a method for determining the iodine adsorption value of active carbon of GB/T12496.8-1999; the caramel decolorization rate is measured by referring to the method for measuring the caramel decolorization rate of the activated carbon GB/T12496.9-1999; the mechanical strength was measured by the method for measuring the mechanical strength of activated carbon "GB/T12496.6-1999".

Example 1

Optimization of the decolorization Process

In this example, in order to obtain a better decoloring effect, activated carbon (including granular activated carbon) with different parameters such as different mesh numbers, iodine values, mechanical strength, caramel decoloring rate and the like was screened.

The method comprises the following specific steps:

1) setting a standard example: in a reaction flask, 10g of crude VB6 (crude purity 99.0%) is dissolved with 50g of water at an elevated temperature, 1.4g of powdered pharmaceutical 767 activated carbon is added at 80 ℃, stirred for 1h, filtered, and the transmittance and HPLC purity of the filtrate are measured to obtain the following results: the filtrate had a transmittance of 0.72 and an HPLC purity of 99.6. The decolorized vitamin B6 solution was set as a standard solution. This standard example can give a higher quality decolorized solution. However, since the standard example uses powdered activated carbon, it cannot be applied to decoloring with a decoloring column and is merely used as a reference standard for the decoloring effect.

2) Sampling different types and specifications of granular activated carbon respectively, wherein the serial number is 1-13#, and the parameters of each granular activated carbon are shown in table 1:

TABLE 1 physical parameters of different granular activated carbons

Activated carbon numbering	Number of meshes	Iodine value (mg/g)	Mechanical Strength (%)	Caramel decolorization ratio (%)
					1#	20-30	860	45.0	99
2#	20-30	1100	30.1	100
					3#	10-20	800	60.2	90
4#	10-15	850	80.1	91
					5#	10-20	820	90.1	88
6#	10-20	960	76.5	92
					7#	30-60	850	50.1	90
8#	20-40	880	50.3	90
					9#	10-20	870	64.5	88
10#	10-40	850	46.9	90
					11#	20-40	1090	53.1	100
12#	30-50	1050	51.2	98
					13#	30-50	1000	69.0	100

The granular activated carbon numbered as above was decolorized by the same method as in step 1), and the results of the decolorization are shown in Table 2.

TABLE 2 decolorization effect of different granular activated carbon after simple decolorization

"/" indicates that the color of the destaining solution was dark and the transmittance was not measured.

As can be seen from Table 2, the decolorized solutions of # 2, # 11, # 12 and # 13 are all pale yellow, which indicates that the activated carbon with higher iodine value has better decolorization capability of vitamin B6.

Therefore, the activated carbons # 2, # 11, # 12 and # 13 were loaded into a decolorizing column and further examined for decolorizing effect according to the following method:

decolorizing column conditions: the glass decolorizing column with the volume of 45ml has the length of 18cm and the inner diameter of 1.8cm, is provided with a clamping sleeve, the bottom of the column is provided with a discharge hole, the top of the column is provided with a feed inlet and a temperature measuring port, and the temperature measuring point is 1cm away from the upper interface of the active carbon. The bottom is a perforated glass baffle.

A column filling step: before filling granular active carbon, glass beads with the diameter of 2mm are filled in the bottom of the decoloring column in advance and the height of the glass beads is 3 cm; then, about 10g of activated carbon was charged.

And (3) decoloring: preparing a vitamin B6 crude product and distilled water into a vitamin B6 crude product solution according to the proportion of 1:5, then feeding the vitamin B6 crude product solution into a feeding hole of a decolorizing column, wherein the feeding temperature is 80 +/-2 ℃, the retention time is about 55-65min, monitoring the transmittance of the solution at a discharging hole in real time, stopping decolorizing when the transmittance is reduced to be below 0.73, calculating the using amount of activated carbon according to the using amount of the vitamin B6 crude product, and further detecting the decolorized solution, wherein the specific results are as follows:

table 3 further decolorization results for different granular activated carbons

As can be seen from table 3, the activated carbons # 2, # 11 and # 12 all can achieve better decolorizing effect with low activated carbon usage. The 2# activated carbon has low mechanical strength, is fragile, generates more powdered carbon for a long time, causes more broken carbon in a decolored solution, needs to be added with a subsequent process to remove the broken carbon, and is not beneficial to industrial production;

the granular active carbon No. 12 has good decolorizing effect, but the HPLC purity of the decolorized solution is about 97.81 percent and is lower than that of the decolorized solution No. 2 and No. 11.

The dosage, the carbon crushing amount and the HPLC purity of the decolored liquid of the 11# granular active carbon are ideal, and the decolored effect is good. Therefore, 11# activated carbon is selected to decolorize the crude vitamin B6 product.

The 13# active carbon has better decolorizing effect, and the dosage of the active carbon is obviously higher than that of 2#, 11# and 12 #. This suggests that too high mechanical strength may result in a decrease in the decoloring efficiency of vitamin B by the activated carbon, resulting in an increase in the amount used.

Example 2

Multi-column series connection decolorization device

In order to further improve the decolorization effect, the inventor develops a multi-column series system, taking the 11# activated carbon in example 1 as an example, but the protection scope of the invention is not limited to the example. The method comprises the following specific steps:

s1: assembling a decoloring device:

s1-1: a plurality of decolorizing columns (5 or more) of the following specifications were prepared: the volume of the glass material is 500ml, the length is 55cm, the inner diameter is 3.4cm, the glass material is provided with a clamping sleeve, the bottom of the column is provided with a discharge hole, the top of the column is provided with a feed inlet and a temperature measuring port, the temperature measuring point is 1cm on the upper interface of the active carbon, and the bottom of the column is provided with a perforated glass baffle.

S1-2: the multiple decolorizing columns are filled with glass beads with diameter of 2mm and height of 10cm, and then filled with No. 11 activated carbon with column height of 39-40cm, and distilled water is added to the upper interface of the activated carbon.

S1-3: optionally selecting several of the above-mentioned assembled decolorizing columns and respectively labeling, for example, selecting 4 columns, respectively labeled as No. 1, 2, 3, 4, and connecting in series according to the manner shown in FIG. 1 to obtain a set of serially connected decolorizing columns. Wherein, the decolorizing column of which the feed inlet is not connected with the rest decolorizing columns is a feed column, and the decolorizing column of which the discharge outlet is not connected with the rest decolorizing columns is a discharge column. For example, as shown in FIG. 1, when the number of columns is 4, column No. 1 is a feed column, columns No. 2-3 are intermediate columns, and column No. 4 is a discharge column.

S2: preparing a crude product solution

400g of crude vitamin B6 product is added into a 2L four-mouth reaction flask equipped with a thermometer, a spherical condenser tube and a mechanical stirring rod, 2000g of distilled water is added, mechanical stirring is carried out until the vitamin B6 product is completely dissolved, and the mixture is heated to the internal temperature of 80 +/-2 ℃ for later use. A dark brown crude solution was obtained, and the transmittance of the crude solution was measured to find that it was 0.012.

S3: decolorizing with feed (taking four columns in series as an example)

Circulating hot water at 95 ℃ is respectively introduced into the jacket of the decolorizing column and is heated to the temperature of 80 +/-2 ℃ at the temperature measuring point. The hot distilled water with the temperature of 80 ℃ is pumped from the feeding hole of the No. 1 column by a peristaltic pump at the speed of 50ml/min until the No. 4 column effluent has no powdered carbon. The remaining decolourisation column was treated in a similar manner (80 ℃ hot distilled water washed to no powdered charcoal).

Connecting the discharge port of the No. 4 column with a receiving bottle, feeding the crude vitamin B6 solution from the feed port of the No. 1 column at a feeding speed of 20-30ml/min, preferably 25-26ml/min, allowing the solution to stay for 30-40min, and controlling the temperature of the temperature measuring point of each decolorizing column to be 80 +/-2 ℃. After the feeding is started, the transmittance and the purity are respectively measured by sampling from the discharge ports of the No. 1 column and the No. 4 column at intervals of about 2 hours. When the transmittance of the No. 4 column effluent decreased to 0.73, the feed was suspended. At this time, the transmittance of the column No. 1 effluent was 0.24, indicating that the activated carbon in column No. 1 was in an adsorption saturated state.

And then, separating the column No. 1 from the column No. 2, and connecting the feed inlet of the new decolorizing column with the discharge outlet of the column No. 4 (marked as column No. 5), wherein the column No. 2 is a feed column and the column No. 5 is a discharge column. The discharge port of the No. 5 column is connected with a receiving bottle, and the crude vitamin B6 solution is fed from the feed port of the No. 2 column in the manner described above. The steps are circularly carried out, namely, when the transmittance of the decoloration liquid at the discharge hole is reduced to 0.73, the decoloring column is replaced according to the mode until all the crude vitamin B6 solution is decolored. At this time, a total of 4 decolorizing columns were replaced. The decolorized solutions were then mixed, sampled and their transmittance and HPLC purity measured.

And (3) decoloring result: total carbon consumption: 454g, total amount of crude vitamin B6: 17566g, the proportion of the active carbon in the total amount of the crude vitamin B6: 2.59 percent, the transmittance of the destaining solution is 0.85 percent, and the HPLC purity of the destaining solution is 99.7 percent.

In the decoloring method, optionally, the replaced decoloring column is eluted by 500ml of 80 ℃ distilled water alone, and the eluent is used as distilled water to prepare a crude vitamin B6 solution. Then taking out the activated carbon in the column, filling new activated carbon in the column, washing the column with hot distilled water at 80 ℃ until no powdered carbon exists, and using the column as a new decoloring column; collecting the extracted activated carbon for subsequent treatment.

From the results of example 1 and example 2, it can be seen that in example 2, the amount of activated carbon is effectively reduced by adopting a multi-column series system and replacing the saturated decolorizing column on the basis of maintaining the decolorizing quality.

Example 3

Recycling of granular activated carbon

3.1 recovery and regeneration of granular activated carbon

In order to further reduce the amount of activated carbon, a method of recovering and reusing activated carbon is generally used. However, the inventors have found that the decolorization ability of the 11# activated carbon is greatly reduced when the 11# activated carbon saturated in the vicinity of the adsorption region is recovered by a conventional elution recovery method.

The activated carbon used for decoloring the crude vitamin B6 in the example is calcined to remove the adsorbed impurities, and the regeneration recovery rate is about 90%.

Fresh 11# activated carbon iodine value 1090, intensity 53.1, caramel decolorization 100, and the regenerated activated carbon after recovery is 1060, 52.6, 98 respectively.

Based on the above, the inventor applies the activated carbon with saturated adsorption in example 2 to the decolorization system with multiple columns connected in series after calcining and regenerating. The method comprises the following specific steps: the separated activated carbon collected in example 2 was calcined and recovered to obtain recovered activated carbon. The physical parameters of the recovered activated carbon are as follows: iodine number 1060, strength 52.6, caramel decolorization 98, the remaining properties were the same as those of the 11# activated carbon described above.

3.2 decolorization Using regenerated granular activated carbon

The crude vitamin B6 solution was decolorized using the recovered activated carbon (all using the regenerated granular activated carbon recovered in 3.1) according to the method of example 2, and the decolorized solution transmittance, HPLC purity, and vitamin B6 yield were measured.

And (3) decoloring result: total carbon consumption: 401g, total amount of crude vitamin B6: 14680g, the proportion of active carbon in the total amount of vitamin B6 crude product: 2.73% (since this example uses the activated carbon used in example 2 after calcination and recovery, the ratio of the total activated carbon used to the total amount of all crude vitamin B6 was actually 1.41%), decolorized liquid transmittance: 0.83, and the HPLC purity of the decolorized solution is 99.6 percent.

Comparing example 2 with example 3, it can be seen that when all the calcined and recovered activated carbon is applied to the multi-column series system of example 2, the good decolorization effect can be obtained, and the total amount of the activated carbon can be further reduced.

Example 4

Preparation of finished vitamin B6 product

The decolorized solutions obtained in examples 2 and 3 were collected, concentrated, crystallized, filtered, washed, and dried according to the method described in journal of Chinese pharmaceutical industry, 2004,35 (1): 1-2, to obtain vitamin B6.

Wherein the total yield of the product corresponding to the decolored solution of example 2 is 96.5%, and the total yield of the product corresponding to the decolored solution of example 3 is 96.3%. The product quality meets the requirements of CP2015, EP9.0 and USP 38.

Comparative example 1

Decolorizing with regenerated granular activated carbon by a single-column decolorizer

The crude vitamin B6 solution was decolorized as follows, using granular activated carbon all as the recovered activated carbon of example 3:

And (3) decoloring: preparing a vitamin B6 crude product and distilled water into a vitamin B6 crude product solution according to the proportion of 1:5, then feeding the vitamin B6 crude product solution into a feeding hole of a decolorizing column, wherein the feeding temperature is 80 +/-2 ℃, the retention time is about 55-65min, monitoring the transmittance of the solution at the discharging hole in real time, stopping decolorizing when the transmittance is reduced to be below 0.73, replacing a new decolorizing column, and continuously decolorizing according to the method until all vitamin B6 crude products are decolorized. The decolorized solution transmittance, HPLC purity, and vitamin B6 yield were measured as described in the above examples.

And (3) decoloring result: total carbon consumption: 402g, total amount of crude vitamin B6: 4203g, the proportion of the active carbon in the total amount of the crude vitamin B6: 9.56 percent, the transmittance of the decolored solution is 0.81, the HPLC purity of the decolored solution is 98.2 percent, and the yield of the vitamin B6 is 94.0 percent.

Comparing example 3 with comparative example 1, it can be seen that when the calcined and regenerated activated carbon is used for decolorization, if only a single decolorization column is used for decolorization and then the decolorization column is used for disposal, and a multi-column series system is not used, the consumption of the activated carbon is greatly increased, and the decolorization effect and the yield are reduced.

All documents referred to herein are incorporated by reference into this application as if each were individually incorporated by reference. Furthermore, it should be understood that various changes and modifications of the present invention can be made by those skilled in the art after reading the above teachings of the present invention, and these equivalents also fall within the scope of the present invention as defined by the appended claims.

Claims

1. A method for decoloring vitamin B6, which is characterized by comprising the following steps:

2. The method of claim 1, wherein the granular activated carbon has the following characteristics:

(a) the iodine value of the granular activated carbon is 1000-1200 mg/g;

(b) the mesh number of the granular active carbon is 10-80 meshes;

(c) the mechanical strength of the granular activated carbon is 40-80%; and

3. The method of claim 1, wherein said crude vitamin B6 solution has one or more characteristics selected from the group consisting of:

1) the vitamin B6 crude product is prepared by an oxazole method;

2) the solvent of the crude vitamin B6 solution is water or an aqueous solvent;

4. The method of claim 1, wherein the granular activated carbon has one or more of the following characteristics:

5. The method of claim 1, wherein step (2) is characterized by one or more of the following features:

1) the feeding is batch feeding or continuous feeding;

6. The method as claimed in claim 1, wherein the total filling height of the granular activated carbon of the n decolorizing columns is 100-.

7. The method of claim 1, wherein the method further comprises the steps of:

8. The method of claim 1, wherein the method further comprises the steps of: the decolorizing column was washed with water until no powdered charcoal was used.

9. A crude vitamin B6 decolorization device, characterized in that, the device includes:

(a) the iodine value of the granular activated carbon is 1000-1200 mg/g;

(b) the mesh number of the granular active carbon is 10-80 meshes;

(c) the mechanical strength of the granular activated carbon is 40-80%; and

10. The apparatus of claim 9, wherein the decolorizing column further comprises one or more of the following features: