CN108558707A - A kind of preparation method of three creatines HMB salt - Google Patents
A kind of preparation method of three creatines HMB salt Download PDFInfo
- Publication number
- CN108558707A CN108558707A CN201810333001.6A CN201810333001A CN108558707A CN 108558707 A CN108558707 A CN 108558707A CN 201810333001 A CN201810333001 A CN 201810333001A CN 108558707 A CN108558707 A CN 108558707A
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- CN
- China
- Prior art keywords
- preparation
- hmb
- creatine
- alcohol
- creatines
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- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
- 238000002360 preparation method Methods 0.000 title claims abstract description 18
- CVSVTCORWBXHQV-UHFFFAOYSA-N creatine Chemical compound NC(=[NH2+])N(C)CC([O-])=O CVSVTCORWBXHQV-UHFFFAOYSA-N 0.000 claims abstract description 46
- 229960003624 creatine Drugs 0.000 claims abstract description 25
- 239000006046 creatine Substances 0.000 claims abstract description 25
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 15
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims abstract description 13
- 238000002425 crystallisation Methods 0.000 claims abstract description 8
- 238000000926 separation method Methods 0.000 claims abstract description 7
- 230000008025 crystallization Effects 0.000 claims abstract description 4
- 238000005406 washing Methods 0.000 claims abstract description 4
- 238000001035 drying Methods 0.000 claims abstract description 3
- 239000011541 reaction mixture Substances 0.000 claims description 11
- 238000006243 chemical reaction Methods 0.000 claims description 8
- 238000001816 cooling Methods 0.000 claims description 8
- 238000001291 vacuum drying Methods 0.000 claims description 3
- 230000001476 alcoholic effect Effects 0.000 claims description 2
- 230000035484 reaction time Effects 0.000 claims description 2
- 239000002904 solvent Substances 0.000 claims description 2
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 21
- 239000013078 crystal Substances 0.000 description 11
- 238000000034 method Methods 0.000 description 7
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 6
- 239000012141 concentrate Substances 0.000 description 5
- 238000004821 distillation Methods 0.000 description 5
- 235000019441 ethanol Nutrition 0.000 description 5
- 239000012535 impurity Substances 0.000 description 5
- 238000011084 recovery Methods 0.000 description 5
- 238000003756 stirring Methods 0.000 description 5
- ZXEKIIBDNHEJCQ-UHFFFAOYSA-N isobutanol Chemical compound CC(C)CO ZXEKIIBDNHEJCQ-UHFFFAOYSA-N 0.000 description 4
- -1 HMB-Na Chemical class 0.000 description 3
- 210000000663 muscle cell Anatomy 0.000 description 3
- 150000003839 salts Chemical class 0.000 description 3
- HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 description 2
- 229910052500 inorganic mineral Inorganic materials 0.000 description 2
- 239000011707 mineral Substances 0.000 description 2
- 210000003205 muscle Anatomy 0.000 description 2
- 241000124008 Mammalia Species 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 210000000577 adipose tissue Anatomy 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
- 230000010261 cell growth Effects 0.000 description 1
- 235000012000 cholesterol Nutrition 0.000 description 1
- 208000029078 coronary artery disease Diseases 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 230000000857 drug effect Effects 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 230000012010 growth Effects 0.000 description 1
- 239000005556 hormone Substances 0.000 description 1
- 229940088597 hormone Drugs 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 125000001909 leucine group Chemical class [H]N(*)C(C(*)=O)C([H])([H])C(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 108010022197 lipoprotein cholesterol Proteins 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 238000006386 neutralization reaction Methods 0.000 description 1
- 235000015097 nutrients Nutrition 0.000 description 1
- 210000002381 plasma Anatomy 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 238000007086 side reaction Methods 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 230000001256 tonic effect Effects 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C277/00—Preparation of guanidine or its derivatives, i.e. compounds containing the group, the singly-bound nitrogen atoms not being part of nitro or nitroso groups
- C07C277/08—Preparation of guanidine or its derivatives, i.e. compounds containing the group, the singly-bound nitrogen atoms not being part of nitro or nitroso groups of substituted guanidines
-
- 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
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Oil, Petroleum & Natural Gas (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention discloses a kind of preparation methods of three creatines HMB salt.Creatine and HMB are first dissolved in the alcohol solution being mixed to form by alcohol, water by the preparation method, then are crystallized, washed, dry through separation successively after by elder generation, and three creatine HMB salt are obtained.The present invention is reacted with creatine and HMB in alcohol solution, then successively through separation crystallization, washing, drying, step is simple, improves yield.
Description
Technical field
The present invention relates to the technical field of creatine more particularly to a kind of preparation methods of three creatines HMB salt.
Background technology
HMB is the metabolite of leucine in human body.United States Patent (USP) reports that it can enhance the immunocompetence of mammal
(US 4992470) promotes human muscle to grow (US 5028440), reduces body fat, i.e., total cholesterol and low in blood
Density lipoprotein-cholesterol is to reduce the generation of coronary heart disease and angiocardiopathy.In order to obtain preferable oral administration biaavailability,
HMB currently on the market is water-soluble preferable mineral salt such as HMB-Na, HMB-K, HMB-Ca.These mineral salts water in vivo
It is absorbed after solution, since this absorption pattern limits the amount into the active HMB of blood plasma, to affect drug effect.
Creatine is primarily present in the liver of animal, as a kind of big right nutrient, can be promoted muscle cell growth, be increased
The growth synthesis for adding the water content of muscle cell, helping muscle cell storage energy, increasing protein, therefore can be highly effective
It improves the endurance of muscle strength and human body and improves sports achievement in ground.Creatine is not hormone, and creatine, which is not present, in human body relies medicine
Property or physiological side reaction, therefore creatine is a kind of safe nourishing tonic for sport.
Three creatine HMB salt are a kind of salt containing creatine cations, HMB anion.Existing report is to it in the prior art
Preparation method.
Invention content
In view of this, the present invention provides a kind of preparation method of three creatines HMB salt, the yield of the preparation method is higher, closes
It is simple at step.
The preparation method of the three creatine HMB salt of the present invention, includes the following steps：
（1）Creatine and HMB are dissolved in the alcohol-water solution being mixed to form by alcohol, water, and are allowed to react；
（2）It will be through step（1）Obtained reaction mixture is crystallized after through separation by elder generation, is washed, dry successively, obtains three creatines
HMB salt.
It is aforementioned, step（1）In；Reaction is the amino by creatine（Basic group）With the carboxyl of HMB（Acidic-group）Hair
Raw neutralization reaction.The temperature of the reaction is preferably 10~60 DEG C.At a temperature of this, the reaction time is 0.5~5h.
The volume of alcohol and water is 1 better：2~8.
Preferably, alcohol C1~4Alcohol, such as methanol, ethyl alcohol, isopropanol, isobutanol etc..
It is aforementioned, step（2）In：The separation crystallization is crystallisation by cooling.Herein, crystallisation by cooling refers to by cooling so that molten
The dissolubility of matter reduces and makes solution supersaturation, the method to precipitate crystal.
Preferably, the cooling temperature of crystallisation by cooling is 2~6 DEG C.
Dry mode is vacuum drying, or other modes.
As a preferred mode, vacuum drying temperature is 60~80 DEG C.
Washing uses alcoholic solvent.
The present invention is reacted with creatine and HMB in alcohol-water solution, then successively through separation crystallization, washing, drying, step is simple,
Improve yield.
Specific implementation mode
The technical solution further illustrated the present invention with reference to embodiment.
Embodiment 1
It is 1 that volume ratio is added in three-necked flask：2 methanol, the mixed liquor of water, then put into creatine and HMB（Creatine molal quantity：
Molal quantity=3.1 HMB:1）, stir and the two be completely dissolved, reaction system is maintained to react 5h at a temperature of 10 DEG C, obtain anti-
Answer mixed liquor.
To the reaction mixture distillation and concentration to liquor capacity to 1/3~2/5, concentrate is formed.6 DEG C are being cooled to analysis
Go out white crystal.The white crystal is washed with absolute methanol to remove impurity.It is dried in vacuo at 60 DEG C again.After tested, this example
Middle total recovery is 95.2%.
Embodiment 2
It is 1 that volume ratio is added in three-necked flask：8 ethyl alcohol, the mixed liquor of water, then put into creatine and HMB（Creatine molal quantity：
Molal quantity=2.8 HMB:1）, stir and the two be completely dissolved, maintain reaction system to react 0.5h at a temperature of 60 DEG C, obtain
Reaction mixture.
To the reaction mixture distillation and concentration to liquor capacity to 1/3~2/5, concentrate is formed.2 DEG C are being cooled to analysis
Go out white crystal.The white crystal is washed with absolute methanol to remove impurity.It is dried in vacuo at 80 DEG C again.After tested, this example
Middle total recovery is 96.0%.
Embodiment 3
It is 1 that volume ratio is added in three-necked flask：5 isopropanol, the mixed liquor of water, then put into creatine and HMB（Creatine mole
Number：Molal quantity=3 HMB:1）, stir and the two be completely dissolved, maintain reaction system to react 1h at a temperature of 40 DEG C, obtain
Reaction mixture.
To the reaction mixture distillation and concentration to liquor capacity to 1/3~2/5, concentrate is formed.3 DEG C are being cooled to analysis
Go out white crystal.The white crystal is washed with absolute methanol to remove impurity.It is dried in vacuo at 70 DEG C again.After tested, this example
Middle total recovery is 98.6%.
Embodiment 4
It is 1 that volume ratio is added in three-necked flask：5 isobutanol, the mixed liquor of water, then put into creatine and HMB（Creatine mole
Number：Molal quantity=3.2 HMB:1）, stir and the two be completely dissolved, maintain reaction system to react 1h at a temperature of 40 DEG C, obtain
To reaction mixture.
To the reaction mixture distillation and concentration to liquor capacity to 1/3~2/5, concentrate is formed.3 DEG C are being cooled to analysis
Go out white crystal.The white crystal is washed with absolute methanol to remove impurity.It is dried in vacuo at 70 DEG C again.After tested, this example
Middle total recovery is 97.7%.
Embodiment 5
It is 1 that volume ratio is added in three-necked flask：5 isopropanol, the mixed liquor of water, then put into creatine and HMB（Creatine mole
Number：Molal quantity=3 HMB:1）, stir and the two be completely dissolved, maintain reaction system to react 2h at a temperature of 40 DEG C, obtain
Reaction mixture.
To the reaction mixture distillation and concentration to liquor capacity to 1/3~2/5, concentrate is formed.4 DEG C are being cooled to analysis
Go out white crystal.The white crystal is washed with absolute methanol to remove impurity.It is dried in vacuo at 70 DEG C again.After tested, this example
Middle total recovery is 96.9%.
Since the numberical range of each technological parameter involved in the present invention can not possibly all embody in the above-described embodiments,
As long as but those skilled in the art's envisioned any numerical value fallen into the above-mentioned numberical range completely can implement this
Invention also includes the arbitrary combination of occurrence in several numberical ranges certainly.Herein, for length the considerations of, be omitted to
Go out the embodiment of occurrence in certain one or more numberical range, this disclosure for being not to be construed as technical scheme of the present invention is not filled
Point.
Applicant states that the present invention illustrates detailed process equipment and the technological process of the present invention by above-described embodiment,
But the invention is not limited in above-mentioned detailed process equipment and technological processes, that is, it is above-mentioned detailed not mean that the present invention has to rely on
Process equipment and technological process could be implemented.Person of ordinary skill in the field it will be clearly understood that any improvement in the present invention,
The addition of equivalence replacement and auxiliary element to each raw material of product of the present invention, the selection etc. of concrete mode all fall within the present invention's
Within protection domain and the open scope.
Claims (9)
1. a kind of preparation method of three creatines HMB salt, which is characterized in that include the following steps：
（1）Creatine and HMB are dissolved in the alcohol-water solution being mixed to form by alcohol, water, and are allowed to react；
（2）It will be through step（1）Obtained reaction mixture is crystallized after through separation by elder generation, is washed, dry successively, obtains three creatines
HMB salt.
2. the preparation method of SC 69124 according to claim 1, which is characterized in that step（1）In：The temperature of the reaction
Degree is 10~60 DEG C, and the reaction time is 0.5~5h.
3. preparation method according to claim 1, which is characterized in that step（1）In：The volume ratio of the alcohol and water is 1：
2~8.
4. preparation method according to claim 1, which is characterized in that step（1）In：The alcohol is C1~4Alcohol.
5. preparation method according to claim 1, which is characterized in that step（2）In：The separation crystallization is cooling knot
It is brilliant.
6. preparation method according to claim 5, which is characterized in that the cooling temperature of the crystallisation by cooling is 2~6 DEG C.
7. preparation method according to claim 1, which is characterized in that step（2）In：The mode of the drying is dry for vacuum
It is dry.
8. preparation method according to claim 1, which is characterized in that the vacuum drying temperature is 60~80 DEG C.
9. preparation method according to claim 1, which is characterized in that step（2）In：The washing uses alcoholic solvent.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201810333001.6A CN108558707A (en) | 2018-04-13 | 2018-04-13 | A kind of preparation method of three creatines HMB salt |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201810333001.6A CN108558707A (en) | 2018-04-13 | 2018-04-13 | A kind of preparation method of three creatines HMB salt |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN108558707A true CN108558707A (en) | 2018-09-21 |
Family
ID=63535008
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201810333001.6A Pending CN108558707A (en) | 2018-04-13 | 2018-04-13 | A kind of preparation method of three creatines HMB salt |
Country Status (1)
| Country | Link |
|---|---|
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Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1434025A (en) * | 2003-02-21 | 2003-08-06 | 华东师范大学 | Process for preparing 3-hydroxy-3-methylbutyrate (HMB) amino acid salt |
| US20050215640A1 (en) * | 2004-03-26 | 2005-09-29 | Baxter Jeffrey H | HMB compositions and uses thereof |
| CN101704767A (en) * | 2009-10-30 | 2010-05-12 | 黄再新 | Preparation method of 3-oxhydryl-3-methylbutyrate creatine |
| WO2017222043A1 (en) * | 2016-06-24 | 2017-12-28 | 協和発酵バイオ株式会社 | Crystal of β-hydroxy β-methylbutyric acid amino acid salt and production method therefor |
-
2018
- 2018-04-13 CN CN201810333001.6A patent/CN108558707A/en active Pending
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1434025A (en) * | 2003-02-21 | 2003-08-06 | 华东师范大学 | Process for preparing 3-hydroxy-3-methylbutyrate (HMB) amino acid salt |
| US20050215640A1 (en) * | 2004-03-26 | 2005-09-29 | Baxter Jeffrey H | HMB compositions and uses thereof |
| CN101704767A (en) * | 2009-10-30 | 2010-05-12 | 黄再新 | Preparation method of 3-oxhydryl-3-methylbutyrate creatine |
| WO2017222043A1 (en) * | 2016-06-24 | 2017-12-28 | 協和発酵バイオ株式会社 | Crystal of β-hydroxy β-methylbutyric acid amino acid salt and production method therefor |
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| PB01 | Publication | ||
| PB01 | Publication | ||
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| SE01 | Entry into force of request for substantive examination | ||
| WD01 | Invention patent application deemed withdrawn after publication | ||
| WD01 | Invention patent application deemed withdrawn after publication |
Application publication date: 20180921 |