CN108129294A - A kind of HMB-Ca manufacturing technique methods - Google Patents
A kind of HMB-Ca manufacturing technique methods Download PDFInfo
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- CN108129294A CN108129294A CN201810058413.3A CN201810058413A CN108129294A CN 108129294 A CN108129294 A CN 108129294A CN 201810058413 A CN201810058413 A CN 201810058413A CN 108129294 A CN108129294 A CN 108129294A
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C51/00—Preparation of carboxylic acids or their salts, halides or anhydrides
- C07C51/41—Preparation of salts of carboxylic acids
- C07C51/412—Preparation of salts of carboxylic acids by conversion of the acids, their salts, esters or anhydrides with the same carboxylic acid part
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C51/00—Preparation of carboxylic acids or their salts, halides or anhydrides
- C07C51/16—Preparation of carboxylic acids or their salts, halides or anhydrides by oxidation
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C51/00—Preparation of carboxylic acids or their salts, halides or anhydrides
- C07C51/42—Separation; Purification; Stabilisation; Use of additives
- C07C51/43—Separation; Purification; Stabilisation; Use of additives by change of the physical state, e.g. crystallisation
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Abstract
The invention discloses a kind of manufacturing technique methods of β hydroxyls β methylbutanoic acids calcium (HMB Ca), including β hydroxyl β methylbutanoic acids (HMB) are dissolved in water, add in calcium salt, stir, filter, being concentrated to give HMB Ca crude products；HMB Ca crude products add in alcoholic solvent, and agitation and filtration adds in organic solvent, agitation and filtration after concentration, solid dries to obtain HMB Ca products；Aperture is 1~100 micron during filtering.HMB Ca manufacturing technique methods of the present invention optimize the operation of HMB Ca productions and purifying filter condition, effectively reduce mechanical admixture and metal ion residual in HMB Ca products, improve safety of the HMB Ca products as health products and food additives；Process conditions are mildly easy to operate, reduce the safe operation grade of production, environmentally protective, are advantageously implemented industrialization.
Description
Technical field
The present invention relates to technical field of organic synthesis more particularly to a kind of manufacturing technique methods of HMB-Ca.
Background technology
Compound beta-hydroxy-Beta-methyl calcium butyrate, abbreviation HMB-Ca are a kind of metabolites of leucine.HMB-Ca can
For animal muscle to be promoted to grow, enhance the immunocompetence of mammal, reduce cholesterol in human body and low-density lipoprotein
(LDL) it is horizontal to reduce the generation of coronary heart disease and angiocardiopathy, moreover it is possible to human body is helped to supplement calcium, enhances human body nitrogen fixing capacity,
Maintain vivo protein horizontal；Therefore application is very extensive, can be used as food additives, dietary supplement, diet food addition
Agent etc. is added to beverage class, milk and milk products, cocoa products, chocolate and chocolate and candy, bakery, special
In dietary food product, play and replenish the calcium, lose weight, moulding the health-care effects such as flesh, strengthen immunity, prevention of cardiovascular disease.
The existing disclosed preparation methods of HMB-Ca use 4- methyl -4- hydroxyls -2 pentanone (diacetone alcohol) and oxidant more
Then reaction, acidification generation beta-hydroxy-Beta-methyl butyric acid obtain HMB-Ca with carrying out salt-forming reaction containing calcon.HMB-Ca makees
For health products and food additives, mechanical admixture and metal ion residual content are required high.In HMB-Ca laboratories preparation side
When method is amplified production, the equipment such as reaction kettle and stirring can introduce new mechanical admixture in production, increase HMB-Ca products
Middle metal ion residual.Therefore, the small-scale preparation method Parameter Conditions in the laboratory of HMB-Ca cannot meet the need of amplification production
Will, it needs to optimize and revise conditional parameter when the technique for carrying out HMB-Ca products amplifies production, need in optimized production process
HMB-Ca product subsequent purification operating methods are wanted with meeting HMB-Ca products in terms of mechanical admixture and metal ion quality
It asks.Also, it is insufficient to still have following several respects for the small-scale preparation method in HMB-Ca laboratories disclosed in the prior art：
(1) preparation method step is more, and complex process is not easy to operate, severe reaction conditions, and total recovery is low；(2) it is generated in preparation process
A large amount of waste water and waste liquids pollute environment；(3) inflammable and explosive reagent is used, it is dangerous big, it feeds intake and post-processing operation is cumbersome, cost
Height is unfavorable for industrializing.In view of many defects of above-mentioned existing preparation method and in view of existing preparation method cannot meet work
The quality requirement of skill amplification production HMB-Ca products.Therefore, a kind of technological operation is simple, cost is relatively low, environmentally protective to developing,
HMB-Ca product mechanical impurities and metal ion residual meet the requirements, and industrialized HMB-Ca manufacturing technique methods is suitble to exist and are compeled
It is essential and asks.
Invention content
In order to solve above-mentioned the deficiencies in the prior art, the object of the present invention is to provide a kind of new HMB-Ca productions
Process.This method has simple for process, and easy to operate, environment friendly and pollution-free, yield is high, of low cost, and technological operation is safe, right
It is environmental-friendly non-stimulated, easily realize the features such as industrialization mass produces.
To achieve the above object, the present invention provides a kind of HMB-Ca manufacturing technique methods, including HMB-Ca crude products are added
Enter alcoholic solvent, agitation and filtration adds in organic solvent, agitation and filtration after filtrate concentration, and solid dries to obtain HMB-Ca products；Wherein,
Aperture is 1~100 micron during the filtering.
Further, the HMB-Ca manufacturing technique methods, include the following steps：
Step 1, beta-hydroxy-Beta-methyl butyric acid are soluble in water, add in containing calcon, stirring obtains mixed liquor after 1~6 hour；
The mixed liquor that step 1 obtains is filtered by step 2, and filtrate concentration obtains solid HMB-Ca crude products after going water removal；
Step 3 adds in alcoholic solvent into the solid that step 2 obtains, and increases temperature and is cooled to room after stirring 1~6 hour
Temperature；
Step 4, step 3 is cooled down after mixed liquor be filtered, filtrate concentration removal alcoholic solvent after solid；
Step 5, the solid obtained to step 4 add in organic solvent, and filtering, drying, obtain HMB- after stirring 1~6 hour
Ca products.
Further, the alcoholic solvent is methanol, ethyl alcohol, propyl alcohol, isopropanol, butanol, isobutanol；The organic solvent is
Ethyl acetate, methyl acetate, butyl acetate, methyl tertiary butyl ether(MTBE)；
Further, in the step 1, the w/v (grams per milliliter) of beta-hydroxy-Beta-methyl butyric acid and water is 1:5
~1:6；
Further, in the step 1, beta-hydroxy-Beta-methyl butyric acid is 1 with the molar ratio containing calcon:1~1:1.2；
Further, it is a kind of in calcium hydroxide, calcium oxide, calcium carbonate, calcium acetate containing calcon in the step 1
Or multiple combinations；
Further, in the step 3, the volume for adding in alcoholic solvent is：The weight of beta-hydroxy-Beta-methyl butyric acid and alcoholic solvent
It is 1 to measure volume ratio (grams per milliliter):2~1:4；
Further, in the step 3, alcoholic solvent is selected from methanol, ethyl alcohol；Preferred alcohol；
Further, in the step 3, raising temperature is 60~80 DEG C；Preferably 70~75 DEG C；
Further, in the step 2 or 4, one or more combinations in sand core, filter cloth, filter membrane are used during filtering；
Further, the use of the aperture of sand core, filter cloth, filter membrane it is 1~50 micron during filtering in the step 2 or 4；It is excellent
It is selected as 1~20 micron；
Further, in the step 5, organic solvent is organic solvent after filtering；Wherein, during filtering using sand core,
One or more combinations in filter cloth, filter membrane using the aperture of sand core, filter cloth, filter membrane are 1~50 micron during filtering；
Further, in the step 5, the volume for adding in organic solvent is：Beta-hydroxy-Beta-methyl butyric acid and organic solvent
W/v (grams per milliliter) be 1:2~1:4；
Further, in the step 5, organic solvent is ethyl acetate.
In the better embodiment of the present invention, in the step 1, mixing time is 2~3 hours；
In the better embodiment of the present invention, in the step 3, mixing time is 1~2 hour；
In the better embodiment of the present invention, in the step 3, the volume for adding in alcoholic solvent is：Beta-hydroxy-Beta-methyl
The w/v of butyric acid and alcoholic solvent (grams per milliliter) is 1:2；
In another better embodiment of the present invention, in the step 3, the volume for adding in alcoholic solvent is：Beta-hydroxy-β-
The w/v of methylbutanoic acid and alcoholic solvent (grams per milliliter) is 1:3；
In another better embodiment of the present invention, in the step 3, the volume for adding in alcoholic solvent is：Beta-hydroxy-β-
The w/v of methylbutanoic acid and alcoholic solvent (grams per milliliter) is 1:4；
In the better embodiment of the present invention, in the step 2 or 4, during filtering using sand core, filter cloth, filter membrane hole
Diameter is 1~20 micron；
In another better embodiment of the present invention, in the step 2 or 4, sand core, filter cloth, filter membrane are used during filtering
Aperture be 1~10 micron；
In another better embodiment of the present invention, in the step 2 or 4, sand core, filter cloth, filter membrane are used during filtering
Aperture be 10~20 microns；
In another better embodiment of the present invention, in the step 2 or 4, sand core, filter cloth, filter membrane are used during filtering
Aperture be 20~30 microns；
In another better embodiment of the present invention, in the step 2 or 4, sand core, filter cloth, filter membrane are used during filtering
Aperture be 30~50 microns；
In the better embodiment of the present invention, in the step 5, mixing time is 1~2 hour；
In the better embodiment of the present invention, in the step 5, organic solvent is organic solvent after filtering；Wherein,
Using sand core, filter cloth, one or more combinations in filter membrane during filtering, during filtering using the aperture of sand core, filter cloth, filter membrane for 1~
20 microns；
In another better embodiment of the present invention, in the step 5, organic solvent is organic solvent after filtering；
Wherein, during filtering using sand core, filter cloth, one or more combinations in filter membrane, during filtering using sand core, filter cloth, filter membrane aperture
It is 1~10 micron；
In another better embodiment of the present invention, in the step 5, organic solvent is organic solvent after filtering；
Wherein, during filtering using sand core, filter cloth, one or more combinations in filter membrane, during filtering using sand core, filter cloth, filter membrane aperture
It is 10~20 microns；
In another better embodiment of the present invention, in the step 5, organic solvent is organic solvent after filtering；
Wherein, during filtering using sand core, filter cloth, one or more combinations in filter membrane, during filtering using sand core, filter cloth, filter membrane aperture
It is 20~30 microns；
In another better embodiment of the present invention, in the step 5, organic solvent is organic solvent after filtering；
Wherein, during filtering using sand core, filter cloth, one or more combinations in filter membrane, during filtering using sand core, filter cloth, filter membrane aperture
It is 30~50 microns；
In the better embodiment of the present invention, in the step 5, the volume for adding in organic solvent is：Beta-hydroxy-β-first
The w/v of base butyric acid and organic solvent (grams per milliliter) is 1:2；
In another better embodiment of the present invention, in the step 5, the volume for adding in organic solvent is：Beta-hydroxy-
The w/v of Beta-methyl butyric acid and organic solvent (grams per milliliter) is 1:3；
In another better embodiment of the present invention, in the step 5, the volume for adding in organic solvent is：Beta-hydroxy-
The w/v of Beta-methyl butyric acid and organic solvent (grams per milliliter) is 1:4；
In the better embodiment of the present invention, in the step 1, the production technology of beta-hydroxy-Beta-methyl butyric acid includes：
Diacetone alcohol is added in aqueous oxidizing agent solution, stirring is stood, layering, and upper strata reaction solution is taken to be quenched, and adjusts pH value 2~3, extraction
Agent is taken to extract, merges the drying of extraction organic phase, filters, is concentrated to give beta-hydroxy-Beta-methyl butyric acid；Wherein, the oxidant and two
The molar ratio of pyruvic alcohol is 2:1~2.9:1, the aqueous oxidizing agent solution is hypohalite aqueous solution, and the extractant is dichloro
One or more combinations in methane, chloroform, methyl acetate, ethyl acetate, isobutanol, n-butanol.
Further, the production technology of the beta-hydroxy-Beta-methyl butyric acid includes the following steps：
Step 1-1,0~15 DEG C of temperature is controlled, diacetone alcohol is added in 5%~20% hypohalite aqueous solution, room temperature
Stirring 1~6 hour is stood, and divides sub-cloud liquid, washs upper strata reaction solution；
Step 1-2, quencher is added in into the upper strata reaction solution of step 1-1, it is 2~3 that pH value is adjusted in stirring, and reduced pressure is gone
Water removal, filters to obtain beta-hydroxy-Beta-methyl butyric acid crude product solution；
Step 1-3, it adds in extractant to the obtained beta-hydroxy-Beta-methyl butyric acid crude product solutions of step 1-2 to be extracted, close
And organic phase drying is extracted, filters, be concentrated to give beta-hydroxy-Beta-methyl butyric acid.
Further, in the step 1-1, diacetone alcohol is with hypohalite aqueous solution w/v (grams per milliliter)
1:10~1:20；
Further, in the step 1-1, hypohalite is sodium hypochlorite, sodium hypobromite；
Or in the step 1-1, hypohalite adds the homemade hypohalite aqueous solution of hydrogen-oxygen salt dissolving for halogen；
Further, the hypohalite aqueous solution adds the homemade hypohalite aqueous solution of hydrogen-oxygen salt dissolving for halogen；Wherein,
Halogen is selected from fluorine, chlorine, bromine, iodine, and hydrogen-oxygen salt dissolving is selected from sodium hydroxide, potassium hydroxide, calcium hydroxide；
Further, in the step 1-1, controlled at 10~15 DEG C；Mixing time is 3~5 hours；
Further, in the step 1-2, quencher is 1 with hypohalite aqueous solution w/v (grams per milliliter):
50~1:100；
Further, in the step 1-2, quencher is sodium hydrogensulfite；
Further, in the step 1-2, stirring adjusts pH value controlled at 10~20 DEG C；
Further, in the step 1-2, stirring adjusts pH value to add in concentrated hydrochloric acid solution, diacetone alcohol and concentrated hydrochloric acid solution
W/v (grams per milliliter) is 1:1~1:3；
Further, in the step 1-3, the w/v (grams per milliliter) of diacetone alcohol and extractant is 1:5~1:
10；
Further, in the step 1-3, extractant is ethyl acetate, isobutanol；
Further, in the step 1-3, drying time is 2~18 hours；Thickening temperature is 60~90 DEG C；
In the better embodiment of the present invention, in the step 1-1, diacetone alcohol and hypohalite aqueous solution weighing body
Product is 1 than (grams per milliliter):15~1:18；
In the better embodiment of the present invention, in the step 1-1, hypohalite aqueous solution is controlled at 0~5
DEG C, 10~15 DEG C of temperature control when adding in diacetone alcohol；
In the better embodiment of the present invention, in the step 1-1, mixing time is 4 hours；
In the better embodiment of the present invention, in the step 1-1, hypohalite aqueous solution is molten for 10% sodium hypochlorite
Liquid
In the better embodiment of the present invention, in the step 1-1, hypohalite aqueous solution adds sodium hydroxide for chlorine element
Homemade aqueous sodium hypochlorite solution；
In the better embodiment of the present invention, in the step 1-2, quencher and hypohalite aqueous solution bulking value
It is 1 than (grams per milliliter):85~1:90；
In another better embodiment of the present invention, in the step 1-2, quencher and hypohalite aqueous solution weight
Volume ratio (grams per milliliter) is 1:85；
In the better embodiment of the present invention, in the step 1-2, stirring adjusts pH value to add in concentrated hydrochloric acid solution, dipropyl
Keto-alcohol is 1 with concentrated hydrochloric acid solution w/v (grams per milliliter):1~1:2；
In another better embodiment of the present invention, in the step 1-2, stirring adjusts pH value to add in concentrated hydrochloric acid solution,
Diacetone alcohol is 1 with concentrated hydrochloric acid solution w/v (grams per milliliter):1.9；
In the better embodiment of the present invention, in the step 1-3, the w/v of diacetone alcohol and extractant
(grams per milliliter) is 1:8~1:9；
In the better embodiment of the present invention, in the step 1-3, drying time is 4~6 hours；
In the better embodiment of the present invention, in the step 1-3, thickening temperature is 75~80 DEG C.
It can described in step, solvent, reagent, filtering, concentration, drying in the above-mentioned HMB-Ca manufacturing technique methods of the present invention etc.
In any combination/split, the object of the invention can be achieved.
Compared with prior art, the manufacturing technique method of HMB-Ca products of the invention, using beta-hydroxy-β-first of optimization
The preparation condition of base butyric acid compound, the HMB-Ca productions operation of optimization and purifying filter condition, effectively reduce HMB-
Mechanical admixture and metal ion residual, improve safety of the HMB-Ca products as health products and food additives in Ca products
Property；
The HMB-Ca manufacturing technique methods of the present invention, route is short, and step is few, and technological operation is easy, and reaction condition is mildly easy
Operation, reduces cost, improves the total recovery of HMB-Ca products；
HMB-Ca manufacturing technique methods of the present invention do not use inflammable and explosive reagent, dangerous low, feed intake and post-processing operation
Simply, the safe operation grade of production cost and production is greatly reduced, it is environmentally protective, be conducive to industrial amplification production.
HMB-Ca manufacturing technique methods of the present invention optimize beta-hydroxy-Beta-methyl butyric acid midbody compound purification process,
Intermediate product purity is made to be more than 98.5%, the miscellaneous content of acetic acid list is not higher than 0.5%, reduces the residual of crucial single miscellaneous acetic acid,
Be conducive to the purifying of finished product, be conducive to improve quality and the extensive use of finished product；
In conclusion HMB-Ca manufacturing technique methods of the present invention, optimize the production operation of HMB-Ca products and purified
Filter condition effectively reduces mechanical admixture and metal ion residual in HMB-Ca products, improves HMB-Ca products as health care
The safety of product and food additives；Optimize beta-hydroxy-Beta-methyl butyric acid midbody compound purification process, obtained HMB-
Ca purity is high, high-quality；It avoids using inflammable and explosive reagent, process conditions are mildly easy to operate, reduce the safe operation of production
Grade, it is environmentally protective, it is advantageously implemented industrialization.
The technique effect of the design of the present invention, specific technical solution and generation is made below with reference to embodiment further
Illustrate, to be fully understood from the purpose of the present invention, feature and effect.
Specific embodiment
Multiple preferred embodiments of the present invention introduced below make its technology contents more clear and are easy to understand.The present invention
Can be emerged from by many various forms of embodiments, these embodiments be exemplary description, protection model of the invention
Enclose the embodiment for being not limited only to mention in text.
If there is test method without specific conditions, usually according to normal condition, such as instructions book or handbook
Implemented.
The production operation of embodiment 1, beta-hydroxy-Beta-methyl butyric acid
10 DEG C step 1, control of temperature, the diacetone alcohol of 80Kg are added in 1200L aqueous sodium hypochlorite solutions (10%), room
Temperature stirring 4 hours, stratification divide sub-cloud liquid, wash upper strata reaction solution；
Step 2 takes the sodium hydrogensulfite that 14Kg is added in the upper strata reaction solution of step 1, and 10 DEG C of stirrings of temperature control add in dense salt
Acid solution 160L, it is 2 to adjust pH value, and reduced pressure goes to remove water, and filters to obtain beta-hydroxy-Beta-methyl butyric acid crude product solution；
Step 3, the ethyl acetate of beta-hydroxy-Beta-methyl butyric acid crude product solution addition 640L obtained to step 2 are extracted
It takes, merging extraction is organic to be added to anhydrous sodium sulfate drying 4 hours, filters, beta-hydroxy-β-first that 60 DEG C of filtrate is concentrated to give 63Kg
Base butyric acid compound.
After testing, in the beta-hydroxy obtained-Beta-methyl butyric acid compound products, beta-hydroxy-Beta-methyl butyric acid content is
98.7%, the miscellaneous content of acetic acid list is 0.5%.
The production operation of embodiment 2, beta-hydroxy-Beta-methyl butyric acid
15 DEG C step 1, control of temperature, the diacetone alcohol of 150Kg is added in 2700L aqueous sodium hypochlorite solutions (15%),
It is stirred at room temperature 5 hours, stratification, divides sub-cloud liquid, wash upper strata reaction solution；
Step 2 takes the sodium hydrogensulfite that 27Kg is added in the upper strata reaction solution of step 1, and 20 DEG C of stirrings of temperature control add in dense salt
Acid solution 150L, it is 3 to adjust pH value, and reduced pressure goes to remove water, and filters to obtain beta-hydroxy-Beta-methyl butyric acid crude product solution；
Step 3, the ethyl acetate of beta-hydroxy-Beta-methyl butyric acid crude product solution addition 1350L obtained to step 2 are extracted
Take, merge extraction it is organic be added to anhydrous sodium sulfate dry 6 hours, filtering, 90 DEG C of filtrate be concentrated to give 114Kg beta-hydroxy-β-
Methylbutanoic acid compound.
After testing, in the beta-hydroxy obtained-Beta-methyl butyric acid compound products, beta-hydroxy-Beta-methyl butyric acid content is
98.6%, the miscellaneous content of acetic acid list is 0.48%.
The production operation of embodiment 3, beta-hydroxy-Beta-methyl butyric acid
5 DEG C step 1, control of temperature, the diacetone alcohol of 200Kg are added in 2000L aqueous sodium hypochlorite solutions (20%), room
Temperature stirring 3 hours, stratification divide sub-cloud liquid, wash upper strata reaction solution；
Step 2 takes the sodium hydrogensulfite that 40Kg is added in the upper strata reaction solution of step 1, and 15 DEG C of stirrings of temperature control add in dense salt
Acid solution 600L, it is 2 to adjust pH value, and reduced pressure goes to remove water, and filters to obtain beta-hydroxy-Beta-methyl butyric acid crude product solution；
Step 3, the isobutanol of beta-hydroxy-Beta-methyl butyric acid crude product solution addition 1000L obtained to step 2 are extracted
Take, merge extraction it is organic be added to anhydrous sodium sulfate dry 18 hours, filtering, 80 DEG C of filtrate be concentrated to give 162Kg beta-hydroxy-β-
Methylbutanoic acid compound.
After testing, in the beta-hydroxy obtained-Beta-methyl butyric acid compound products, beta-hydroxy-Beta-methyl butyric acid content is
99.1%, the miscellaneous content of acetic acid list is 0.46%.
The production operation of embodiment 4, beta-hydroxy-Beta-methyl butyric acid
10-15 DEG C step 1, control of temperature, the diacetone alcohol of 50Kg is added in 1000L sodium hypobromites aqueous solution (5%),
It is stirred at room temperature 1 hour, stratification, divides sub-cloud liquid, wash upper strata reaction solution；
Step 2 takes the sodium hydrogensulfite that 11Kg is added in the upper strata reaction solution of step 1, and 10 DEG C of stirrings of temperature control add in dense salt
Acid solution 95L, it is 2 to adjust pH value, and reduced pressure goes to remove water, and filters to obtain beta-hydroxy-Beta-methyl butyric acid crude product solution；
Step 3, the ethyl acetate of beta-hydroxy-Beta-methyl butyric acid crude product solution addition 500L obtained to step 2 are extracted
It takes, merging extraction is organic to be added to anhydrous sodium sulfate drying 2 hours, filters, beta-hydroxy-β-first that 75 DEG C of filtrate is concentrated to give 38Kg
Base butyric acid compound.
After testing, in the beta-hydroxy obtained-Beta-methyl butyric acid compound products, beta-hydroxy-Beta-methyl butyric acid content is
98.9%, the miscellaneous content of acetic acid list is 0.48%.
By described above as it can be seen that beta-hydroxy-Beta-methyl butyric acid compound products content that the embodiment of the present invention 1~4 produces
More than 98.5%, the miscellaneous content of acetic acid list is not higher than 0.5% in product, and yield is more than 74%.
Embodiment 5, HMB-Ca production technology operating methods
The beta-hydroxy of 50Kg-Beta-methyl butyric acid is dissolved in 250L water by step 1, adds in the calcium hydroxide of 1 equivalent 95%,
Stirring obtains mixed liquor after 2 hours；
Mixed liquor in step 1 is carried out sand core filtering by step 2, and sand core aperture is 10-20 microns, pads 400 mesh filter clothes and paving
Diatomite, filtrate concentration obtain solid HMB-Ca crude products after going water removal；
Step 3, the ethyl alcohol that 100L is added in into the HMB-Ca crude products that step 2 obtains, raising temperature is to 70 DEG C and stirring 2 is small
When after be cooled to room temperature；
Step 4, step 3 is cooled down after mixed liquor carry out sand core filtering, sand core aperture be 10-20 micron, filtrate concentrate
Solid is obtained after removing alcohol solvent；
Step 5, the ethyl acetate for taking 100L carry out sand core filtering, and sand core aperture is 10-20 microns, and step 4 is obtained
It is added in solid in the ethyl acetate of above-mentioned processing, filtering, drying after stirring 2 hours, obtaining HMB-Ca products, (95Kg is received
Rate 82%).
Embodiment 6, HMB-Ca production technology operating methods
The beta-hydroxy of 80Kg-Beta-methyl butyric acid is dissolved in 480L water by step 1, adds in the calcium oxide of 1.1 equivalents, stirring 3
Hour obtains mixed liquor；
Mixed liquor in step 1 is carried out filter-cloth filtering by step 2, and filter cloth aperture is 1-10 microns, after water removal is gone in filtrate concentration
Obtain solid HMB-Ca crude products；
Step 3, the methanol that 240L is added in into the HMB-Ca crude products that step 2 obtains, raising temperature is to 75 DEG C and stirring 1 is small
When after be cooled to room temperature；
Step 4, step 3 is cooled down after mixed liquor carry out filter-cloth filtering, filter cloth aperture be 1-10 micron, filtrate concentrate go
Except after methanol solvate solid；
Step 5, the ethyl acetate for taking 240L carry out filter-cloth filtering, and filter cloth aperture is 1-10 microns, and step 4 is obtained
It is added in solid in the ethyl acetate of above-mentioned processing, filtering, drying after stirring 5 hours, obtaining HMB-Ca products, (165Kg is received
Rate 89%).
Embodiment 7, HMB-Ca production technology operating methods
The beta-hydroxy of 100Kg-Beta-methyl butyric acid is dissolved in 550L water by step 1, adds in the calcium carbonate of 1.2 equivalents, stirring
Obtain mixed liquor within 2 hours；
Mixed liquor in step 1 is carried out filter-cloth filtering by step 2, and filter cloth aperture is 30-50 microns, and filtrate concentration goes to remove water
Solid HMB-Ca crude products are obtained afterwards；
Step 3, the ethyl alcohol that 400L is added in into the HMB-Ca crude products that step 2 obtains, raising temperature is to 60 DEG C and stirring 3 is small
When after be cooled to room temperature；
Step 4, step 3 is cooled down after mixed liquor carry out membrane filtration, filter sizes be 30-50 micron, filtrate concentrate
Solid is obtained after removing alcohol solvent；
Step 5, the ethyl acetate for taking 400L carry out membrane filtration, and filter sizes are 30-50 microns, and step 4 is obtained
It is added in solid in the ethyl acetate of above-mentioned processing, filtering, drying after stirring 1 hour, obtaining HMB-Ca products, (203Kg is received
Rate 87%).
Embodiment 8, HMB-Ca production technology operating methods
The beta-hydroxy of 150Kg-Beta-methyl butyric acid is dissolved in 825L water by step 1, adds in the hydroxide of 1.1 equivalents 95%
Calcium, stirring obtain mixed liquor in 6 hours；
Mixed liquor in step 1 is carried out sand core filtering by step 2, and sand core aperture is 20-30 microns, pads 400 mesh filter clothes and paving
Diatomite, filtrate concentration obtain solid HMB-Ca crude products after going water removal；
Step 3, the ethyl alcohol that 450L is added in into the HMB-Ca crude products that step 2 obtains, raising temperature is to 80 DEG C and stirring 6 is small
When after be cooled to room temperature；
Step 4, step 3 is cooled down after mixed liquor carry out sand core filtering, sand core aperture be 20-30 micron, filtrate concentrate
Solid is obtained after removing alcohol solvent；
Step 5, the ethyl acetate for taking 450L carry out sand core filtering, and sand core aperture is 20-30 microns, and step 4 is obtained
It is added in solid in the ethyl acetate of above-mentioned processing, filtering, drying after stirring 6 hours, obtaining HMB-Ca products, (289Kg is received
Rate 83%).
Test example 9,
(1) the HMB-Ca products obtained to above-described embodiment 5-8 carry out solubility detection：
HMB-Ca product 0.5g are weighed, add in the deionized water of 20mL, sample was completely dissolved at 30 minutes, and solution is in clarification
Transparence colourless solution；
HMB-Ca product 0.5g are weighed, add in the absolute ethyl alcohol of 20mL, sample was completely dissolved at 30 minutes, and solution is in clarification
Transparence colourless solution；
Show HMB-Ca products that process of the embodiment of the present invention the obtains favorable solubility in water and ethyl alcohol, do not contain
The mechanical admixture of slightly solubility；
(2) the HMB-Ca products obtained to above-described embodiment 5-8 carry out metal ion residue detection：
A, lead metal ion residues detect
HMB-Ca product 2g are weighed, add in the deionized water dissolving of 45mL, the hydrochloric acid solution (2.8mol/L) of 5mL is added dropwise,
Filtering；25mL filtrates are taken in colorimetric cylinder, add in 0.5mL, 30% acetic acid solution, 10mL saturated hydrogen sulphide solutions shake up and put
It puts 10 minutes, colorimetric is carried out with standard lead ratio colour tube, the record standard lead ratio colour tube identical with HMB-Ca product solution color and lusters
Lead content；
Testing result shows that lead metal ion concentration is not more than 5ppm in the HMB-Ca products that the embodiment of the present invention obtains；
Show to require lead metal ion concentration no more than 10ppm relative in HMB-Ca target levels of product quality, the present invention
Lead metal ion concentration is not more than 5ppm in the HMB-Ca products that embodiment is prepared, and is significantly less than HMB-Ca product quality marks
To the requirement of lead metal ion concentration in standard；
B, arsenic metal ion residue detection
HMB-Ca product 2g are weighed, add in 30mL nitric acid, 1.25mL sulfuric acid shakes up overnight, solution heating resolution to solution
It is limpid transparent, 20mL pure water is added in, white cigarette has been heated to and has emerged, cooling constant volume is in the colorimetric cylinder of 25mL；Take 20mL above-mentioned molten
Liquid adds in 5mL concentrated hydrochloric acids and 5mL, and 8% potassium borohydride adds in 5mL after heating slightly boiling, and 5% ascorbic acid is settled to 50mL colorimetrics
Guan Zhong carries out colorimetric with standard arsenic colorimetric cylinder, and the arsenic of the record standard arsenic colorimetric cylinder identical with HMB-Ca product solution color and lusters contains
Amount；
Testing result shows that arsenic metal ion content is not more than in the HMB-Ca products that the embodiment of the present invention obtains
0.6ppm；
Show to require arsenic metal ion content no more than 1ppm relative in HMB-Ca target levels of product quality, the present invention
Arsenic metal ion content is not more than 0.6ppm in the HMB-Ca products that embodiment is prepared, and is significantly less than HMB-Ca product qualities
To the requirement of arsenic metal ion content in standard；
Show that the HMB-Ca metal ion neutralization products residual that the embodiment of the present invention is prepared is few, substantially increase HMB-
Ca product qualities and safety in utilization；
(3) the HMB-Ca products obtained to above-described embodiment 5-8 carry out determination of calcium content：
The HMB-Ca obtained using complexometry to above-described embodiment 5-8 carries out the measure of calcium content, titration results
Calcium content is 14.3-14.9%, HMB-Ca total content 99-101% in the HMB-Ca products that the display embodiment of the present invention obtains, and is accorded with
Close the requirement to calcium content and total content in HMB-Ca target levels of product quality.
In conclusion the manufacturing technique method of the HMB-Ca products of the embodiment of the present invention obtains target product by two steps
HMB-Ca, using the preparation condition of beta-hydroxy-Beta-methyl butyric acid compound of optimization, the HMB-Ca productions operation of optimization and
Filter condition is purified, while requirement to calcium and product content in meeting HMB-Ca target levels of product quality, is effectively subtracted
Lack mechanical admixture and metal ion residual in HMB-Ca products, improve HMB-Ca products as health products and food additives
Safety；The process of the embodiment of the present invention optimizes beta-hydroxy-Beta-methyl butyric acid compound purification process, makes intermediate
Product purity is more than 98.5%, and the miscellaneous content of acetic acid list is not higher than 0.5%, reduces the residual of crucial single miscellaneous acetic acid, is conducive to end
The purifying of product, quality are easy to control, and improve the quality of HMB-Ca finished products, and process total recovery is made to be more than 60%；This
Inventive method is avoided using expensive reagent, catalyst, avoids, using inflammable and explosive reagent, reducing safe operation of production etc.
Grade while totle drilling cost is effectively reduced, is advantageously implemented industrialization amplification.
The process of other embodiment technical solution of the present invention and obtained HMB-Ca products have and above-mentioned phase
As advantageous effect.
The preferred embodiment of the present invention described in detail above.It should be appreciated that the ordinary skill of this field is without wound
The property made labour, which according to the present invention can conceive, makes many modifications and variations, and each parameter of preparation method is adjusted in the reasonable scope
It is whole etc..Therefore, all technician in the art under this invention's idea on the basis of existing technology by logic analysis,
Reasoning or the available technical solution of limited experiment, all should be in the protection domain being defined in the patent claims.
Claims (10)
1. a kind of HMB-Ca manufacturing technique methods, which is characterized in that including by HMB-Ca crude products add in alcoholic solvent, agitation and filtration,
Organic solvent, agitation and filtration are added in after filtrate concentration, solid dries to obtain HMB-Ca products；Wherein, during the filtering aperture for 1~
100 microns.
2. method as described in claim 1, which is characterized in that include the following steps：
Step 1, beta-hydroxy-Beta-methyl butyric acid are soluble in water, add in containing calcon, stirring obtains mixed liquor after 1~6 hour；
The mixed liquor that step 1 obtains is filtered by step 2, and filtrate concentration obtains solid HMB-Ca crude products after going water removal；
Step 3 adds in alcoholic solvent into the solid that step 2 obtains, and increases temperature and is cooled to room temperature after stirring 1~6 hour；
Step 4, step 3 is cooled down after mixed liquor be filtered, filtrate concentration removal alcoholic solvent after solid；
Step 5, the solid obtained to step 4 add in organic solvent, and filtering, drying after stirring 1~6 hour obtain HMB-Ca productions
Product；
Wherein, the calcon that contains is one or more combination in calcium hydroxide, calcium oxide, calcium carbonate, calcium acetate.
3. method as claimed in claim 1 or 2, which is characterized in that the alcoholic solvent is methanol, ethyl alcohol, propyl alcohol, isopropanol, fourth
Alcohol, isobutanol；The organic solvent is methyl acetate, ethyl acetate, butyl acetate, methyl tertiary butyl ether(MTBE).
4. method as claimed in claim 1 or 2, which is characterized in that during the filtering using sand core, filter cloth, in filter membrane it is a kind of or
Multiple combinations；The aperture using sand core, filter cloth, filter membrane is 1~50 micron.
5. method as claimed in claim 2, which is characterized in that in the step 3,
Alcoholic solvent is selected from methanol, ethyl alcohol；
Add in alcoholic solvent volume be：The w/v of beta-hydroxy-Beta-methyl butyric acid and alcoholic solvent is 1:2~1:4.
6. method as claimed in claim 2, which is characterized in that in the step 5,
Organic solvent is ethyl acetate；
Add in organic solvent volume be：The w/v of beta-hydroxy-Beta-methyl butyric acid and organic solvent is 1:2~1:4.
7. method as claimed in claim 2, which is characterized in that in the step 1, the production work of beta-hydroxy-Beta-methyl butyric acid
Skill includes：Diacetone alcohol is added in aqueous oxidizing agent solution, stirring is stood, layering, and upper strata reaction solution is taken to be quenched, adjusts pH value 2
~3, extractant extraction merges the drying of extraction organic phase, filters, is concentrated to give beta-hydroxy-Beta-methyl butyric acid；Wherein, the oxidation
The molar ratio of agent and diacetone alcohol is 2:1~2.9:1；The aqueous oxidizing agent solution is hypohalite aqueous solution；The extractant
For one or more combinations in dichloromethane, chloroform, methyl acetate, ethyl acetate, isobutanol, n-butanol.
8. method as claimed in claim 7, which is characterized in that the production technology of the beta-hydroxy-Beta-methyl butyric acid includes following
Step：
Step 1-1,0~15 DEG C of temperature is controlled, diacetone alcohol is added in 5%~20% hypohalite aqueous solution, is stirred at room temperature 1
It~6 hours, stands, divides sub-cloud liquid, wash upper strata reaction solution；
Step 1-2, quencher is added in into the upper strata reaction solution of step 1-1, it is 2~3 that pH value is adjusted in stirring, and removal is concentrated under reduced pressure
Water filters to obtain beta-hydroxy-Beta-methyl butyric acid crude product solution；
Step 1-3, it adds in extractant to the obtained beta-hydroxy-Beta-methyl butyric acid crude product solutions of step 1-2 to be extracted, merges extraction
Organic phase drying is taken, filters, be concentrated to give beta-hydroxy-Beta-methyl butyric acid.
9. method as claimed in claim 8, which is characterized in that in the step 1-1, hypohalite is sodium hypochlorite, hypobromous acid
Sodium；
Or in the step 1-1, hypohalite adds the homemade hypohalite aqueous solution of hydrogen-oxygen salt dissolving for halogen.
10. the HMB-Ca that a kind of any one of claim 1~9 process obtains.
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Cited By (3)
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| CN111410605A (en) * | 2020-04-07 | 2020-07-14 | 苏州永健生物医药有限公司 | Preparation method of β -hydroxy- β -calcium methylbutyrate |
| CN112806562A (en) * | 2019-11-15 | 2021-05-18 | 内蒙古蒙牛乳业（集团）股份有限公司 | Weight-reducing composition, weight-reducing preparation and application |
| CN112889987A (en) * | 2019-11-19 | 2021-06-04 | 内蒙古蒙牛乳业（集团）股份有限公司 | Food composition, tablet candy and application |
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