CN110251470A - A kind of vitamin B12The production method of Couteat of Folic Acid - Google Patents
A kind of vitamin B12The production method of Couteat of Folic Acid Download PDFInfo
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- CN110251470A CN110251470A CN201910526980.1A CN201910526980A CN110251470A CN 110251470 A CN110251470 A CN 110251470A CN 201910526980 A CN201910526980 A CN 201910526980A CN 110251470 A CN110251470 A CN 110251470A
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- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
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- A61K31/7135—Compounds containing heavy metals
- A61K31/714—Cobalamins, e.g. cyanocobalamin, i.e. vitamin B12
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Abstract
The present invention relates to a kind of vitamin Bs12The production method of Couteat of Folic Acid includes the following steps: step Sa: weighing folic acid, the vitamin B of formula ratio12Powder, lactose, edible corn starch, magnesium stearate, it is spare；Step Sb: it takes proper amount of edible cornstarch to be added after appropriate purified water stirs into suspension shape and is added in boiling purified water, stir into paste, cool；Step Sc: weighed folic acid and vitamin B is added into paste product obtained by step Sb12Powder stirs evenly spare；Step Sd: remaining edible corn starch and lactose are put into efficient wet mixer-granulator, and adhesive softwood prepared by step Sb and step Sc is added, is then pelletized on oscillating granulator with nylon screen；Step Se: the wet granular made is met the requirements with oven drying to particle weightlessness, and the magnesium stearate of formula ratio is added to the mixer with gained particle after drying and is uniformly mixed；Step Sf: tabletting obtains finished product.
Description
Technical field
The present invention relates to the production and processing technical fields of multivitamin, and in particular to a kind of vitamin B12The production of Couteat of Folic Acid
Method.
Background technique
Folic acid belongs to water-soluble (vitamin) B race, is the general name with a kind of compound of dish acyl glutamate molecule structure,
Also known as dish acyl glutamic acid, folic acid, vitamine M, vitamin B11。
The important physiological function of folic acid is the carrier participation metabolism as one-carbon compound, and derivative tetrahydrofolic acid is with auxiliary
Enzyme form is the carrier of one carbon unit, and the utilization of transfer and formyl and formaldehyde to methyl all plays an important role.
Since the intracorporal folic acid of people is almost completely dependent on food intake, when folic acid intake is insufficient or utilizes
Will be in the presence of folic acid deficiency when rate reduces, in human body.Studies have shown that the core that human body shortage folic acid can cause baby is huge red
The diseases such as cellulous anemia, the macrocytic anemia of pregnant woman, neonatal nervous system abnormality and elderly stroke, because
This, folic acid has highly important medical value and development prospect.
Vitamin B12Also known as cobalamin or cyanogen cobalt element, vitamin B12It is one found so far in B family vitamin the latest
Kind, soluble easily in water and ethyl alcohol is most stable in the case where pH value is the mild acid conditions of 4.5-5.0, decomposes in strong acid or alkaline solution, is pre-
Heat can have to be destroyed to a certain degree, but the high-temperature sterilization loss of short time is small, meets strong light or ultraviolet light is easily destroyed.
Vitamin B12Major function be: 1, promote red blood cell development and maturation, make human body hematopoietic function be in just
Normal state prevents pernicious anaemia, maintenance nervous system health；2, exist in the form of coenzyme, the utilization rate of folic acid can be increased, promote
Into the metabolism of carbohydrate, fat and protein；3, have the function of activated amino acid and promote the biosynthesis of nucleic acid, it can
The synthesis for promoting protein, plays an important role to the growth and development of infant；4, fat metabolism acid, make fat, carbohydrate,
Protein is suitably used by body；5, it eliminates and haves the fidgets, focus on, enhancing memory and the sense of equilibrium；It 6, is nervous system
Function perfects indispensable vitamin, participates in a kind of formation of lipoprotein in nerve fiber.
Therefore, vitamin B12It is taken jointly with folic acid, is capable of providing a kind of preferable maternal nutritional product.
Summary of the invention
The present invention provides a kind of vitamin Bs12The production method of Couteat of Folic Acid, includes the following steps:
Step Sa: folic acid, the vitamin B of formula ratio are weighed12Powder, lactose, edible corn starch, magnesium stearate, it is spare；
Step Sb: taking proper amount of edible cornstarch to be added after appropriate purified water stirs into suspension shape and be added in boiling purified water, stirring
At paste, cool；
Step Sc: weighed folic acid and vitamin B is added into paste product obtained by step Sb12Powder stirs evenly spare；
Step Sd: remaining edible corn starch and lactose are put into efficient wet mixer-granulator, and step Sb and step is added
Adhesive softwood prepared by rapid Sc, is then pelletized on oscillating granulator with nylon screen；
Step Se: the wet granular made is met the requirements with oven drying to particle weightlessness, by the magnesium stearate of formula ratio and is done
Gained particle is added to the mixer uniformly mixed after dry；
Step Sf: tabletting obtains finished product；
Wherein, the vitamin B being added in the step Sc12Powder includes vitamin B12And D-mannital, vitamin B12Production
Method includes:
Step S1: denitrified pseudomonas is seeded in fermentation medium, by fast growing period and after stablizing growth period, is obtained
Obtain vitamin B12Fermentation liquid；
Step S2: to vitamin B12Certain density cellulase and pectase, the pre- timing of magnetic agitation are added in fermentation liquid
Between, make intracellular vitamin B12The dissolution of ingredient broken wall, ultrafiltration membrance filter, obtains supernatant later；
Step S3: iron cyano complex and defomaing agent being added into supernatant, continue the magnetic agitation predetermined time, obtain comprising dimension life
Plain B12Solution；
Step S4: will include vitamin B12Solution after nanofiltration system filters, obtain concentrate and dialyzate；
Step S5: dialyzate is obtained into final vitamin B after repeatedly adsorbing exchange by continuous ionic exchange system12
Eluent, vacuum freeze drying eluent, obtains vitamin B12。
Wherein, in the step S1, fermentation medium includes each ingredient of following quality proportioning: sucrose 80-90g/L, jade
Rice & peanut milk 50-65 g/L, ammonium sulfate 0.5-1.0 g/L, dimethylbenzimidazole 0.05-0.1 g/L, arginine 0.05-0.1 g/
L, yeast extract 100-110 g/L, zinc sulfate 0.5-2.0 g/L, urea 0.03-0.08 g/L, diammonium hydrogen phosphate 0.5-0.8 g/
L, calcium carbonate 0.1-1.5 g/L, phosphoglycerol 0.1-1.0 g/L, potassium dihydrogen phosphate 0.5-1.3 g/L, dipotassium hydrogen phosphate 0.5-
1.3 g/L, magnesia 0.5-0.8 g/L, cobalt chloride 0.05-0.08 g/L, glycine betaine 20-35 g/L, thiamine 0.01-0.03
g/L。
Wherein, in the step S1, the pH value of fermentation medium is controlled between 6.5-7.5 by sucrose and urea.
Wherein, in the step S1, the fermentation period of fast growing period stablized the fermentation in growth period between 65-75 hours
Period was between 75-165 hours；Fast-growth is interim, controls the mixing speed of fermentation medium between 300-350rpm, ventilation speed
Rate uses stabilized light source intermittent irradiation culture medium 6-10 hours between 1.5-1.8LPM, also, daily；Stablize in growth period,
The mixing speed of fermentation medium is controlled between 100-150rpm, Ventilation Rate uses steady daily between 0.5-0.8LPM
Determine light source intermittent irradiation culture medium 3-6 hours.
Wherein, in the step S2, the addition concentration of cellulase and pectase between 8-10g/L, magnetic agitation
Temperature is between 0-4 degrees Celsius, and mixing time was between 2-4 hours；When ultrafiltration membrance filter, filter pressure is between 1.2-1.5MPa.
Wherein, in the step S3, the defomaing agent being added is selected from soya-bean oil or corn oil.
Wherein, big by polyacrylate macroporous absorbent resin and divinylbenzene polymerization respectively in the step S5
Macroporous adsorbent resin adsorbs dialyzate, is eluted with edible ethanol to it, and feed volume 100L, feed rate is between 60-
70mL/min。
Wherein, it in the step S1, when strain is in fast growing period, is spaced after the predetermined time into fermentation medium
Add the nutrients matched as follows: glycine betaine 15-20g/L, sophorose 30-40g/L, cellobiose 10-15g/L, sodium bicarbonate
0.01-0.03g/L, Gardenoside 0.15-0.45g/L, nicotinamide mononucleotide 0.1-0.5g/L, glycosides propylhomoserin 15-20g/L and Soviet Union's ammonia
Sour 15-20g/L.
Wherein, obtained vitamin B12In Couteat of Folic Acid, the quality proportioning difference of each ingredient is as follows: 0.06-0.10 parts of folic acid,
Vitamin B120.01-0.03 parts of powder, 75-80 parts of lactose, 18-20 parts of edible corn starch, 0.6-1.0 parts of magnesium stearate.
Vitamin B provided by the invention12The production method of Couteat of Folic Acid, simple process, at low cost, high income, production process
Security performance is high.
Detailed description of the invention
A kind of Fig. 1: vitamin B provided by the invention12The production technological process of Couteat of Folic Acid.
Specific embodiment
In order to have further understanding to technical solution of the present invention and beneficial effect, it is described in detail with reference to the accompanying drawing
Technical solution of the present invention and its beneficial effect of generation.
Fig. 1 is a kind of vitamin B provided by the invention12The production technological process of Couteat of Folic Acid, as shown in Figure 1, of the invention
The vitamin B of offer12The complete technological process of production of one of Couteat of Folic Acid approximately as:
1, it examines
All supplementary materials, inner packaging material by after the assay was approved can neck enter workshop use.
2, pre-treatment is produced
Preprocessing raw material and auxiliary material: coming into dust proof workshop after the cleaned disinfection of material, spare.
3, it weighs
Folic acid, vitamin B are weighed by batch production expense12Powder (cyanocobalamin, D-mannital), lactose, edible corn starch,
Magnesium stearate contains the container of load weighted material cleaning or material bag, sealing, and in container containing or material bag outer layer
Material label is sticked in significant position, spare.
4, it pelletizes
(1) it prepares adhesive (8% starch slurry): weighing proper amount of edible cornstarch, be added after appropriate purified water stirs into suspension shape
It is added in boiling purified water, stirs into paste, folic acid, the vitamin B of formula ratio are added after cooling12Powder (cyanocobalamin, D-MANNOSE
Alcohol), it stirs evenly spare, obtains adhesive.
(2) remaining starch, formula ratio lactose are poured into efficient wet mixer-granulator, adhesive softwood are added,
Then it is pelletized on oscillating granulator with (24 mesh) nylon screen.
5, dry
The wet granular made is dried with baking oven (55 ± 5 DEG C), drying to particle drying weightlessness meets the requirements, with 24 meshes
Net carries out whole grain to dry particl.
6, total mix
The magnesium stearate for weighing formula ratio is added to the mixer with conforming particle to be uniformly mixed.
7, tabletting
Tabletting, regular check piece appearance and slice weight are carried out by mark weight 0.3g/ piece.
8, inner packing
Dress is wrapped inside by the operating instruction of equipment, clears out a gathering place after production by SOP requirement.
9, outer packing
Capsule packaging, vanning.
Core of the invention inventive point is, by obtaining vitamin B from main fermentation and extraction process12, detailed system
It is as follows to make method:
One, fermentation stage
Denitrified pseudomonas is seeded in fermentation medium, by fast growing period and after stablizing growth period, obtains dimension life
Plain B12Fermentation liquid.
Specifically, fermentation medium of the invention includes each ingredient of following quality proportioning: sucrose 80-90g/L, corn pulp
50-65 g/L, ammonium sulfate 0.5-1.0 g/L, dimethylbenzimidazole 0.05-0.1 g/L, arginine 0.05-0.1 g/L, ferment
Female cream 100-110 g/L, zinc sulfate 0.5-2.0 g/L, urea 0.03-0.08 g/L, diammonium hydrogen phosphate 0.5-0.8 g/L, carbon
Sour calcium 0.1-1.5 g/L, phosphoglycerol 0.1-1.0 g/L, potassium dihydrogen phosphate 0.5-1.3 g/L, dipotassium hydrogen phosphate 0.5-1.3
G/L, magnesia 0.5-0.8 g/L, cobalt chloride 0.05-0.08 g/L, glycine betaine 20-35 g/L, thiamine 0.01-0.03 g/
L.The environment of fermentation medium is preferably neutral environment, and the control of pH value, fermentation training are realized by the addition of sucrose and urea
When supporting base meta-alkalescence, sucrose is added, when slant acidity, adds urea.
In the present invention, by the addition of glycine betaine, capable of guaranteeing fermenting microbe, normally osmotic pressure and cell membrane intracellular are logical
Permeability improves the anti-adversity ability of microorganism in the presence of a harsh environment, improves the accretion rate of nutriment, oxygen and waste.It is logical
The addition of peroxophosphoric acid hydrogen dipotassium and potassium dihydrogen phosphate ensure that potassium concentration certain in fermentation medium, can be effectively
Improve tunning vitamin B12Yield, also, dipotassium hydrogen phosphate and potassium dihydrogen phosphate can provide one to fermentation medium
A excellent buffer environment is conducive to maintain acid-base balance, grows strain in a stable environment.
The effect of fast growing period is that denitrified pseudomonas is made to grow to logarithm growth stage as early as possible, makes strain quantity
It realizes and maximizes, the present invention realizes shortening fast growing period by providing enough dissolved oxygen amounts and illumination, and improves denitrogenation
The effect of strain number after Pseudomonas alba is stable, preferably, the fermentation period of fast growing period is between 65-75 in the present invention
Hour, fast-growth is interim, controls the mixing speed of fermentation medium between 300-350rpm, Ventilation Rate is between 1.5-
1.8LPM, also, it is daily using stabilized light source intermittent irradiation culture medium 6-10 hours.
In addition, can periodically supplement the nutrients into fermentation medium object in fast growing period, terminated with improving fast growing period
The strain number of denitrified pseudomonas afterwards, the nutrient profile and proportion that the present invention adds are as follows: glycine betaine 15-20g/L, sophorose
30-40g/L, cellobiose 10-15g/L, sodium bicarbonate 0.01-0.03g/L, Gardenoside 0.15-0.45g/L, niacinamide monokaryon
Thuja acid 0.1-0.5g/L, glycosides propylhomoserin 15-20g/L and threonine 15-20g/L.The frequency of addition is substantially 10 hours primary, is added
Add ratio between nutrients volume: fermentation medium volume=1:10-1:5.It is demonstrated experimentally that the case where adding proportion is 1:10
Under, strain number after fast growing period, relative to the fermentation medium for not adding nutrients, strain number increases nearly 30%.
After strain enters stable growth period, strain number keeps stablizing, at this point, denitrified pseudomonas fermentation produces vitamin B12
Rate accelerate, in order to which the time cycle extend as far as possible in growth period will be stablized, with improve strain produce vitamin B12Yield, this
In invention, relative to fast growing period, the dissolved oxygen amount and strain lighting conditions of fermentation medium is suitably reduced, is not being influenced
In the case where denitrified pseudomonas normal growth, vitamin B is farthest improved12Yield.Preferably, stablizing growth period
Fermentation period between 75-165 hours；Stablize in growth period, control the mixing speed of fermentation medium between 100-150rpm,
Ventilation Rate uses stabilized light source intermittent irradiation culture medium 3-6 hours between 0.5-0.8LPM, also, daily.
Two, the stage is extracted
1, breaking-wall cell
The fermentation liquid obtained after fermentation exists mostly in the form of intracellular, and therefore, the first step work done to fermentation culture is,
To vitamin B12Certain density cellulase and pectase are added in fermentation liquid, the magnetic agitation predetermined time makes intracellular
Vitamin B12The dissolution of ingredient broken wall, ultrafiltration membrance filter, obtains supernatant later.
The effect of cellulase and pectase is to give birth to dimension the main component-cellulose and pectin of cell wall
Plain B12It is dissolved out from cell with the ingredient of natural stabilisation, the addition concentration of cellulase and pectase is between 8-10g/L, magnetic force
The temperature of stirring is between 0-4 degrees Celsius, and mixing time was between 2-4 hours；Pass through cellulase and the dimension life of pectase extraction
Plain B12, can omit it is existing enzymatic hydrolysis, flocculation and etc., and do not need heating broken wall, the vitamin B after extraction12,
Be originally present in vitamin B12Vitamin B in fermentation liquid12, obtained after filtering can be separated to by ultrafiltration membrance filter
In the supernatant obtained.This broken wall+enzymatic hydrolysis extraction step, avoids the addition of the chemical components such as flocculant, enzymolysis agent, ensure that
Subsequent extracted vitamin B12Purity and safety can be complete also, when cellulase and pectase are through ultrafiltration membrance filter
In full retention to ultrafiltration membrane, impurity will not be brought for subsequent technique, and cellulase and pectase are cheap, safe, will not produce
Raw side effect.
In the present invention, when ultrafiltration membrance filter, filter pressure is preferably between 1.2-1.5MPa.
2, cyanide converts
The vitamin B extracted by breaking-wall cell and ultrafiltration membrance filter12, it is cyano type vitamin B12, mostly with adenosine coenzyme
Form exists, existing by adenosine co-enzyme form vitamin B12It is converted into cyano B12Method, mostly use toxic articles Cymag,
Security risk undoubtedly is brought to shop personnel, the present invention replaces Cymag using iron cyano complex, can not influence
Conversion ratio is improved under the premise of transformation efficiency, reduces security risk.
One preferable conversion reaction is as follows: iron cyano complex and defomaing agent being added into supernatant, continues magnetic agitation
Predetermined time obtains comprising vitamin B12Solution；The defomaing agent being added is selected from soya-bean oil or corn oil, is the edible foam that disappears
Agent will not bring security risk.
3, it filters and dialyses
It (1) will include vitamin B12Solution after nanofiltration system filters, obtain concentrate and dialyzate；
(2) dialyzate is passed through into continuous ionic exchange system after repeatedly adsorbing exchange, obtains final vitamin B12Elution
Liquid, vacuum freeze drying eluent, obtains vitamin B12。
The present invention preferably selects to polymerize macropore suction by polyacrylate macroporous absorbent resin and divinylbenzene respectively
Attached resin adsorbs dialyzate, and the main function of polyacrylate macroporous absorbent resin is to remove most of impurity,
Guarantee the purity of final products, on the one hand the effect of divinylbenzene polymerization macroporous absorbent resin is further to remove remaining miscellaneous
Matter, so that the purity of final products is further increased, on the other hand, inventors have found that divinylbenzene polymerize macroporous absorbent resin
In absorb-elute vitamin B12When, it is stronger to the suction-operated of eluent, but will not influence vitamin B12Elution effect
Therefore fruit after eluent is polymerize macroporous resin adsorption using divinylbenzene, can absorb about 80% eluent, finally obtain
Final mean annual increment solution concentration it is higher, can high degree reduce the cost of subsequent freeze drying process, improve entire technique and produced
The efficiency of journey.
In the present invention, in absorb-elute twice, it is eluted with edible ethanol respectively, feed volume 100L, into
Stream amount is between 60-70mL/min.Ethyl alcohol volatility is stronger, and edible ethanol safety, will not bring side effect to final finished,
Also, the selection of edible ethanol eluent and inventor are considering polyacrylate macroporous absorbent resin and divinyl
Under the premise of benzene polymerize the recuperability of macroporous absorbent resin, selected optimum eluent.
Beneficial effects of the present invention are as follows:
1, by the control of fast growing period and stable growth period difference dissolved oxygen amount and illumination condition, in combination with adding for nutrients
Add, ensure that strain strain number after fast growing period reaches optimum value, and improves strain and stablizing growth period fermentation
Generate vitamin B12Efficiency.
2, pass through pectase and cellulase extraction vitamin B12And the step of ultrafiltration membrance filter, avoid flocculation
The addition of the chemical components such as agent, enzymolysis agent ensure that subsequent extracted vitamin B12Purity and safety.
3, by replacing Cymag to realize vitamin B with iron cyano complex12The conversion of form can not influence conversion effect
Conversion ratio is improved under the premise of rate, reduces the security risk of shop personnel.
4, vitamin B is successively adsorbed by two kinds of different macroporous absorbent resins12The step of, improve the purity of final products
And concentration, high degree reduce the cost of subsequent freeze drying process, improve the efficiency of entire art production process.
5, it by the selection of edible ethanol eluent and the cooperation of itself and two different macroporous absorbent resins, improves
The recuperability of corresponding macroporous absorbent resin.
Although the present invention is illustrated using above-mentioned preferred embodiment, the protection model that however, it is not to limit the invention
It encloses, anyone skilled in the art are not departing within the spirit and scope of the present invention, and opposite above-described embodiment carries out various changes
It is dynamic still to belong to the range that the present invention is protected with modification, therefore protection scope of the present invention subjects to the definition of the claims.
Claims (9)
1. a kind of vitamin B12The production method of Couteat of Folic Acid, which comprises the steps of:
Step Sa: folic acid, the vitamin B of formula ratio are weighed12Powder, lactose, edible corn starch, magnesium stearate, it is spare；
Step Sb: taking proper amount of edible cornstarch to be added after appropriate purified water stirs into suspension shape and be added in boiling purified water, stirring
At paste, cool；
Step Sc: weighed folic acid and vitamin B is added into paste product obtained by step Sb12Powder stirs evenly spare；
Step Sd: remaining edible corn starch and lactose are put into efficient wet mixer-granulator, and step Sb and step is added
Adhesive softwood prepared by rapid Sc, is then pelletized on oscillating granulator with nylon screen；
Step Se: the wet granular made is met the requirements with oven drying to particle weightlessness, by the magnesium stearate of formula ratio and is done
Gained particle is added to the mixer uniformly mixed after dry；
Step Sf: tabletting obtains finished product；
Wherein, the vitamin B being added in the step Sc12Powder includes vitamin B12And D-mannital, vitamin B12Production
Method includes:
Step S1: denitrified pseudomonas is seeded in fermentation medium, by fast growing period and after stablizing growth period, is obtained
Obtain vitamin B12Fermentation liquid；
Step S2: to vitamin B12It is added certain density cellulase and pectase in fermentation liquid, the magnetic agitation predetermined time,
Make intracellular vitamin B12The dissolution of ingredient broken wall, ultrafiltration membrance filter, obtains supernatant later；
Step S3: iron cyano complex and defomaing agent being added into supernatant, continue the magnetic agitation predetermined time, obtain comprising dimension life
Plain B12Solution；
Step S4: will include vitamin B12Solution after nanofiltration system filters, obtain concentrate and dialyzate；
Step S5: dialyzate is obtained into final vitamin B after repeatedly adsorbing exchange by continuous ionic exchange system12
Eluent, vacuum freeze drying eluent, obtains vitamin B12。
2. vitamin B as described in claim 112The production method of Couteat of Folic Acid, which is characterized in that in the step S1, fermentation
Culture medium includes each ingredient of following quality proportioning: sucrose 80-90g/L, corn pulp 50-65 g/L, ammonium sulfate 0.5-1.0 g/
L, dimethylbenzimidazole 0.05-0.1 g/L, arginine 0.05-0.1 g/L, yeast extract 100-110 g/L, zinc sulfate 0.5-
2.0 g/L, urea 0.03-0.08 g/L, diammonium hydrogen phosphate 0.5-0.8 g/L, calcium carbonate 0.1-1.5 g/L, phosphoglycerol
0.1-1.0 g/L, potassium dihydrogen phosphate 0.5-1.3 g/L, dipotassium hydrogen phosphate 0.5-1.3 g/L, magnesia 0.5-0.8 g/L, chlorine
Change cobalt 0.05-0.08 g/L, glycine betaine 20-35 g/L, thiamine 0.01-0.03 g/L.
3. vitamin B as described in claim 112The production method of Couteat of Folic Acid, which is characterized in that in the step S1, pass through
The pH value of sucrose and urea control fermentation medium is between 6.5-7.5.
4. vitamin B as described in claim 112The production method of Couteat of Folic Acid, which is characterized in that in the step S1, quickly
The fermentation period in growth period stablized the fermentation period in growth period between 75-165 hours between 65-75 hours；Fast growing period
In, the mixing speed of fermentation medium is controlled between 300-350rpm, and Ventilation Rate is adopted between 1.5-1.8LPM, also, daily
With stabilized light source intermittent irradiation culture medium 6-10 hours；Stablize in growth period, control the mixing speed of fermentation medium between
100-150rpm, Ventilation Rate are small using stabilized light source intermittent irradiation culture medium 3-6 between 0.5-0.8LPM, also, daily
When.
5. vitamin B as described in claim 112The production method of Couteat of Folic Acid, which is characterized in that in the step S2, fiber
The addition concentration of plain enzyme and pectase between 8-10g/L, the temperature of magnetic agitation between 0-4 degrees Celsius, mixing time between
2-4 hours；When ultrafiltration membrance filter, filter pressure is between 1.2-1.5MPa.
6. vitamin B as described in claim 112The production method of Couteat of Folic Acid, which is characterized in that added in the step S3
The defomaing agent entered is selected from soya-bean oil or corn oil.
7. vitamin B as described in claim 112The production method of Couteat of Folic Acid, which is characterized in that in the step S5, respectively
It polymerize macroporous absorbent resin by polyacrylate macroporous absorbent resin and divinylbenzene to adsorb dialyzate, with food
It is eluted with ethyl alcohol, feed volume 100L, feed rate is between 60-70mL/min.
8. vitamin B as described in claim 112The production method of Couteat of Folic Acid, which is characterized in that in the step S1, in bacterium
When kind is in fast growing period, the nutrients matched as follows: glycine betaine 15- is added into fermentation medium after being spaced the predetermined time
20g/L, sophorose 30-40g/L, cellobiose 10-15g/L, sodium bicarbonate 0.01-0.03g/L, Gardenoside 0.15-0.45g/L,
Nicotinamide mononucleotide 0.1-0.5g/L, glycosides propylhomoserin 15-20g/L and threonine 15-20g/L.
9. vitamin B as described in claim 112The production method of Couteat of Folic Acid, which is characterized in that obtained vitamin B12Folic acid
In piece, the quality proportioning difference of each ingredient is as follows: 0.06-0.10 parts of folic acid, vitamin B120.01-0.03 parts of powder, lactose 75-80
Part, 18-20 parts of edible corn starch, 0.6-1.0 parts of magnesium stearate.
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| CN112480482A (en) * | 2020-11-30 | 2021-03-12 | 河北华北制药华恒药业有限公司 | Fermentation gel homogenizing agent and preparation method and application thereof |
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| CN101176734A (en) * | 2006-11-10 | 2008-05-14 | 江西省药物研究所 | Nutrients replenisher for replenishing folic acid and vitamin B12 and preparation method thereof |
| WO2017011133A1 (en) * | 2015-07-10 | 2017-01-19 | Mjn U.S. Holdings Llc | Nutritional compositions and methods for promoting cognitive development |
| CN108913738A (en) * | 2018-07-28 | 2018-11-30 | 广济药业（孟州）有限公司 | A kind of raising vitamin B based on Dissolved oxygen regulation12The method of yield |
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| CN101176734A (en) * | 2006-11-10 | 2008-05-14 | 江西省药物研究所 | Nutrients replenisher for replenishing folic acid and vitamin B12 and preparation method thereof |
| WO2017011133A1 (en) * | 2015-07-10 | 2017-01-19 | Mjn U.S. Holdings Llc | Nutritional compositions and methods for promoting cognitive development |
| CN108913738A (en) * | 2018-07-28 | 2018-11-30 | 广济药业（孟州）有限公司 | A kind of raising vitamin B based on Dissolved oxygen regulation12The method of yield |
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| CN112480482A (en) * | 2020-11-30 | 2021-03-12 | 河北华北制药华恒药业有限公司 | Fermentation gel homogenizing agent and preparation method and application thereof |
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