CN109438278A - A kind of occrycetin preparation method - Google Patents
A kind of occrycetin preparation method Download PDFInfo
- Publication number
- CN109438278A CN109438278A CN201811472852.5A CN201811472852A CN109438278A CN 109438278 A CN109438278 A CN 109438278A CN 201811472852 A CN201811472852 A CN 201811472852A CN 109438278 A CN109438278 A CN 109438278A
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- Prior art keywords
- occrycetin
- mixed solution
- added
- calcium chloride
- preparation
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C231/00—Preparation of carboxylic acid amides
- C07C231/12—Preparation of carboxylic acid amides by reactions not involving the formation of carboxamide groups
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C231/00—Preparation of carboxylic acid amides
- C07C231/22—Separation; Purification; Stabilisation; Use of additives
- C07C231/24—Separation; Purification
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2603/00—Systems containing at least three condensed rings
- C07C2603/02—Ortho- or ortho- and peri-condensed systems
- C07C2603/40—Ortho- or ortho- and peri-condensed systems containing four condensed rings
- C07C2603/42—Ortho- or ortho- and peri-condensed systems containing four condensed rings containing only six-membered rings
- C07C2603/44—Naphthacenes; Hydrogenated naphthacenes
- C07C2603/46—1,4,4a,5,5a,6,11,12a- Octahydronaphthacenes, e.g. tetracyclines
Abstract
The invention discloses a kind of occrycetin preparation methods comprising: Step 1: Oxytetracycline Base, calcium chloride are added in methyl alcohol, and stir evenly, filtrate is obtained by filtration；Raw material proportioning are as follows: 1500~2100L of methanol, 350~500Kg of Oxytetracycline Base, 35~50Kg of calcium chloride；Step 2: controlling above-mentioned filtrate temperature to 20~26 DEG C, and methanol hydrochloride solution is added to obtain mixed solution, discontinuous stirring is carried out so that occrycetin is precipitated to mixed solution；Wherein contain hydrogen chloride 26Kg in the methanol hydrochloride solution；Step 3: being centrifuged, drying to the mixed solution after precipitation occrycetin, to obtain occrycetin.The present invention has the advantages that the impurity contents such as stable dehydration mycin, α-Ah flutterring-terramycin, β-Ah flutterring-terramycin in 96% or more, product of the mass yield of occrycetin are low.
Description
Technical field
The invention belongs to manufacture method of medicine field, in particular to a kind of occrycetin preparation method.
Background technique
In prior art, the production technology of occrycetin is to select methanol for solvent, is carried out to raw material Oxytetracycline Base
After filtering, hydrochloric acid methanol is added into salt in dissolution；Soil obtains occrycetin after nearly 10 hours standing crystallisation by cooling, centrifugation.
Prior art has the following problems: 1, occrycetin not yet crystal form is not of uniform size, and the mass yield of product is lower than
90%2, the crystallisation by cooling time is long, will increase the impurity such as dehydration terramycin, α-Ah flutterring-terramycin and β-Ah flutterring-terramycin
Content.
Summary of the invention
In order to solve the above technical problems, the present invention provides a kind of occrycetin preparation method, specific technical solution
It is as follows:
A kind of occrycetin preparation method comprising:
Step 1: Oxytetracycline Base, calcium chloride are added in methyl alcohol, and stir evenly, filtrate is obtained by filtration；Raw material proportioning
Are as follows: 1500~2100L of methanol, 350~500Kg of Oxytetracycline Base, 35~50Kg of calcium chloride；
Step 2: controlling above-mentioned filtrate temperature to 20~26 DEG C, and methanol hydrochloride solution is added to obtain mixed solution,
Discontinuous stirring is carried out so that occrycetin is precipitated to mixed solution；Wherein contain hydrogen chloride in the methanol hydrochloride solution
26Kg；
Step 3: the mixed solution after precipitation occrycetin is centrifuged, is dried, it is mould to obtain salt sour soil
Element.
In certain embodiments, the whipping temp in step 1 is 30 DEG C, and mixing speed is 40~60r/min.
In certain embodiments, the discontinuous stirring in step 2 are as follows: stirring total duration is 4h, is stirred in every 30min
5min is mixed, mixing speed is 10~20r/min.
The present invention has the advantages that
1, filtrate temperature is controlled to methanol hydrochloride solution is added within the scope of 20~26 DEG C at salt, to guarantee occrycetin
Crystal form is uniform in size.
2, discontinuous stirred crystallization is conducive to the rapid crystallization of occrycetin and reduces the generation of impurity, of the invention
It is mould to stablize dehydration mycin, α-Ah flutterring-terramycin, β-Ah flutterring-soil in 96% or more, product in the mould mass yield of salt sour soil
The impurity contents such as element are far below state of the art.
Specific embodiment
The present invention will be described in detail With reference to embodiment.
Embodiment one:
Methanol 1500L, Oxytetracycline Base 350Kg, calcium chloride 35Kg are taken, Oxytetracycline Base, calcium chloride are added into methanol simultaneously
It the temperature was then adjusted to 30 DEG C or so, filters after mixing evenly, obtains filtrate.
Then by the control of filtrate temperature within the scope of 24~26 DEG C, the methanol hydrochloride solution of hydrogen chloride 26Kg adds by equivalent
Enter in filtrate to obtain mixed solution.Discontinuous stirring is carried out so that occrycetin, the discontinuous is precipitated to mixed solution
Stirring specifically: stirring total duration is 4h, and 5min is stirred in every 30min, and mixing speed is 15~20r/min.
After discontinuous stirs, the temperature of mixed solution is down to 0 DEG C, and occrycetin is sufficiently precipitated.At this point, to mixing
Solution is centrifuged to obtain occrycetin wet product and mother liquor.
The occrycetin wet product of precipitation is dried to obtain final occrycetin finished product, mother liquor is then delivered to
Fluid reservoir is to realize recycling.
The occrycetin finished product prepared to embodiment one is sampled detection, and testing result is as follows:
Embodiment two:
Methanol 2100L, Oxytetracycline Base 500Kg, calcium chloride 50Kg are taken, Oxytetracycline Base, calcium chloride are added into methanol simultaneously
It the temperature was then adjusted to 30 DEG C or so, filters after mixing evenly, obtains filtrate.
Then by the control of filtrate temperature within the scope of 21~23 DEG C, the methanol hydrochloride solution of hydrogen chloride 26Kg adds by equivalent
Enter in filtrate to obtain mixed solution.Discontinuous stirring is carried out so that occrycetin, the discontinuous is precipitated to mixed solution
Stirring specifically: stirring total duration is 4h, and 5min is stirred in every 30min, and mixing speed is 10~15r/min.
After discontinuous stirs, the temperature of mixed solution is down to 0 DEG C, and occrycetin is sufficiently precipitated.At this point, to mixing
Solution is centrifuged to obtain occrycetin wet product and mother liquor.
The occrycetin wet product of precipitation is dried to obtain final occrycetin finished product, mother liquor is then delivered to
Fluid reservoir is to realize recycling.
The occrycetin finished product prepared to embodiment two is sampled detection, and testing result is as follows:
Still there are many embodiment, all technical sides formed using equivalents or equivalent transformation by the present invention
Case is within the scope of the present invention.
Claims (3)
1. a kind of occrycetin preparation method, characterized in that it comprises:
Step 1: Oxytetracycline Base, calcium chloride are added in methyl alcohol, and stir evenly, filtrate is obtained by filtration；Raw material proportioning are as follows: first
1500~2100L of alcohol, 350~500Kg of Oxytetracycline Base, 35~50Kg of calcium chloride；
Step 2: the temperature of above-mentioned filtrate is adjusted to 20~26 DEG C, and methanol hydrochloride solution is added to obtain mixed solution, it is right
Mixed solution carries out discontinuous stirring so that occrycetin is precipitated；Wherein contain hydrogen chloride 26Kg in the methanol hydrochloride solution；
Step 3: being centrifuged, drying to the mixed solution after precipitation occrycetin, to obtain occrycetin.
2. occrycetin preparation method as described in claim 1, which is characterized in that the whipping temp in step 1 is 30
DEG C, mixing speed is 40~60r/min.
3. occrycetin preparation method as described in claim 1, which is characterized in that the discontinuous stirring in step 2 are as follows:
Stirring total duration is 4h, and 5min is stirred in every 30min, and mixing speed is 10~20r/min.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201811472852.5A CN109438278A (en) | 2018-12-04 | 2018-12-04 | A kind of occrycetin preparation method |
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| Application Number | Priority Date | Filing Date | Title |
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| CN201811472852.5A CN109438278A (en) | 2018-12-04 | 2018-12-04 | A kind of occrycetin preparation method |
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| CN109438278A true CN109438278A (en) | 2019-03-08 |
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| CN201811472852.5A Pending CN109438278A (en) | 2018-12-04 | 2018-12-04 | A kind of occrycetin preparation method |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN112624937A (en) * | 2020-12-23 | 2021-04-09 | 江苏天和制药有限公司 | Drying method of oxytetracycline hydrochloride |
Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE952632C (en) * | 1954-05-25 | 1956-11-22 | Hoechst Ag | Process for the production of tetracyclines from their solutions |
| CN1146451A (en) * | 1995-09-26 | 1997-04-02 | 王洪承 | Improved method for production of oxytetracycline hydrochloride |
| CN101914035A (en) * | 2010-08-27 | 2010-12-15 | 扬州联博药业有限公司 | Method for preparing oxytetracycline hydrochloride |
| CN104513176A (en) * | 2015-01-08 | 2015-04-15 | 内蒙古格林特制药有限责任公司 | Preparation method for oxytetracycline hydrochloride |
| CN107011205A (en) * | 2017-04-12 | 2017-08-04 | 扬州联博药业有限公司 | A kind of method for producing large-grain occrycetin |
| CN107522631A (en) * | 2017-09-13 | 2017-12-29 | 盐城市大丰区天生联合药业有限公司 | A kind of preparation method of occrycetin |
-
2018
- 2018-12-04 CN CN201811472852.5A patent/CN109438278A/en active Pending
Patent Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE952632C (en) * | 1954-05-25 | 1956-11-22 | Hoechst Ag | Process for the production of tetracyclines from their solutions |
| CN1146451A (en) * | 1995-09-26 | 1997-04-02 | 王洪承 | Improved method for production of oxytetracycline hydrochloride |
| CN101914035A (en) * | 2010-08-27 | 2010-12-15 | 扬州联博药业有限公司 | Method for preparing oxytetracycline hydrochloride |
| CN104513176A (en) * | 2015-01-08 | 2015-04-15 | 内蒙古格林特制药有限责任公司 | Preparation method for oxytetracycline hydrochloride |
| CN107011205A (en) * | 2017-04-12 | 2017-08-04 | 扬州联博药业有限公司 | A kind of method for producing large-grain occrycetin |
| CN107522631A (en) * | 2017-09-13 | 2017-12-29 | 盐城市大丰区天生联合药业有限公司 | A kind of preparation method of occrycetin |
Non-Patent Citations (2)
| Title |
|---|
| 中国人民解放军兽医大学药理教研室: "《兽医常用药物制剂》", 30 November 1979 * |
| 刘小梅等: "土霉素碱转盐酸盐的生产工艺改进 ", 《中国医药工业杂志》 * |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN112624937A (en) * | 2020-12-23 | 2021-04-09 | 江苏天和制药有限公司 | Drying method of oxytetracycline hydrochloride |
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