CN1090268A - Production of oxytetracycline hydrochloride - Google Patents
Production of oxytetracycline hydrochloride Download PDFInfo
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- CN1090268A CN1090268A CN 93114290 CN93114290A CN1090268A CN 1090268 A CN1090268 A CN 1090268A CN 93114290 CN93114290 CN 93114290 CN 93114290 A CN93114290 A CN 93114290A CN 1090268 A CN1090268 A CN 1090268A
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- tetramycin hydrochloride
- mother liquor
- terramycin
- acid alcohol
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Abstract
The present invention relates to a kind of new process of production of tetramycin hydrochloride, this novel process be filtrate after decolouring or the centrifugation gained filtrate (being mother liquor) directly the less water that boiling point is high than methyl alcohol from system, separate, thereby mother liquor can directly return dissolving tank for the use of dissolving Oxytetracycline Base BP (98), production process is: in containing the mother liquor lysate of Oxytetracycline Base BP (98), after adding an amount of acid alcohol, use activated carbon decolorizing, mixed solution gets clear liquid after filtration, filter out wherein moisture then, add an amount of acid alcohol again, carry out freezing and crystallizing, can obtain the tetramycin hydrochloride crystallization.Use technology of the present invention, can improve the yield of tetramycin hydrochloride, cut down the consumption of energy, reduce the production cost of tetramycin hydrochloride.
Description
The present invention relates to a kind of new process of production of tetramycin hydrochloride, belong to medicine system affair technical field.
Terramycin has Oxytetracycline Base BP (98) and two kinds of products of tetramycin hydrochloride, and Oxytetracycline Base BP (98) solubleness in water is little, is difficult for being absorbed by the body, and drug effect is slow.Tetramycin hydrochloride solubleness in water is big, easily is absorbed by the body, and curative effect is fast, is suitable for intramuscular injection, the treatment acute disease.After tetramycin hydrochloride added hydrochloric acid by Oxytetracycline Base BP (98), separating purifies made.
The production process of existing tetramycin hydrochloride is as shown in Figure 1: Oxytetracycline Base BP (98) is used dissolve with methanol in dissolving tank, adds the hydrogen chloride methanol solution (abbreviation acid alcohol) that contains HCl 20～40% simultaneously, and adds CaCl
2Make the tetramycin hydrochloride methanol solution, this solution activated carbon decolorizing is removed partial impurities, mixed solution after filtration, isolate behind the solid slag clear liquid, after clear liquid is added an amount of acid alcohol, carry out freezing and crystallizing, separate out the tetramycin hydrochloride crystallization, through centrifugation, and with after the small amount of methanol washing, crystallization, drying again must wet, promptly get the tetramycin hydrochloride finished product, centrifugation gained filtrate is mainly methyl alcohol, wherein contains tetramycin hydrochloride and water, in adding alkali and after reclaim methyl alcohol with distillation method, reuse.Distillation tower still waste liquid directly discharges, and waste liquid is mainly the water and soil mycin, and wherein the main source of water is that institute is moisture in the raw material Oxytetracycline Base BP (98).
The characteristics of this method are in order to remove the water of the system that brought into by raw material Oxytetracycline Base BP (98) etc., adopt distillation method to separate centrifugation gained filtrate (mother liquor), distillation cat head gained Methanol Recovery is used, gained contains the direct discharging of waste water of terramycin at the bottom of the tower, its shortcoming is that the part terramycin loses with discharging of waste liquid, and the yield of tetramycin hydrochloride is low.When distillation method reclaimed methyl alcohol in addition, a large amount of lower boiling methyl alcohol steamed with the gas form from the distillation cat head, and energy consumption is big, so the cost height of tetramycin hydrochloride.
The objective of the invention is filtrate after decolouring or the centrifugation gained filtrate (mother liquor) directly the less water that boiling point is high than methyl alcohol separates from system.Thereby mother liquor can directly return dissolving tank and use for the dissolving Oxytetracycline Base BP (98), avoids terramycin to lose with discharging of waste liquid, improves the tetramycin hydrochloride yield.Deduct the distillation reclaimer operation of methyl alcohol simultaneously, cut down the consumption of energy.
Content of the present invention is: referring to Fig. 2, Oxytetracycline Base BP (98) with the mother liquor dissolving, adds an amount of acid alcohol again in dissolving tank, and the solution composition of making is methyl alcohol 76～78% terramycin 16～18%, water 2～3%, CaCl
2～4%, HCl～0.5% is used activated carbon decolorizing, and the gac add-on is about about 0.1～0.5% of terramycin alkali number, looks how much and suitably increase and decrease of impurity level in the Oxytetracycline Base BP (98).Mixed solution after filtration clear liquid, isolate wherein portion water with the pervaporation membrane separation unit, membrane separation unit is at 70～90 ℃, absolute pressure 1～10Kpa operation down behind the film, the branch output of water equals the water yield of bringing in the acid alcohol of Oxytetracycline Base BP (98) and adding system.Membrane sepn gained refined liquid is added an amount of acid alcohol, carries out freezing and crystallizing under 0 °～-10 ℃, separates out the tetramycin hydrochloride crystallization.With after centrifugation, the crystallization of must wetting, drying promptly gets the tetramycin hydrochloride finished product again.Centrifugation gained filtrate is mother liquor, directly returns the usefulness of dissolving tank for the dissolving raw material terramycin.Total add-on of secondary acid alcohol is determined by following relationship: the HCl add-on is the loss amount of and system required with the Oxytetracycline Base BP (98) reaction production tetramycin hydrochloride that adds, and the methyl alcohol add-on is the loss amount in the system operation.
Description of drawings:
Fig. 1 is the production scheme of tetramycin hydrochloride in the prior art;
Fig. 2 is a new process of production schema of the present invention;
Fig. 3 is another technical process of new process of production of the present invention.
Flow process shown in Figure 3 is that from the difference of Fig. 2 flow process pervaporation dehydrating step position on stream is different. The pervaporation dehydration is after freezing and crystallizing and centrifugation in Fig. 3 flow process, and centrifugation gained filtrate (mother liquor) is directly returned dissolving tank for the usefulness of dissolving raw material terramycin after pervaporation separates water outlet.
Characteristics of the present invention are directly to remove the water of the system of bringing into from the clear liquid (such as Fig. 2 technology) of clean system or mother liquor (such as Fig. 3 technology) with the pervaporation membrane separation process, do not have discharging of waste liquid, the terramycin loss of avoiding old process waste liquor row to cause. Therefore improved the yield of occrycetin, deducted simultaneously and reclaimed the used still-process of methyl alcohol, can cut down the consumption of energy, overall result be can the decrease occrycetin production cost.
Embodiment:
Embodiment 1: get mother liquor 1200kg(and wherein contain methyl alcohol 1107.6kg, tetramycin hydrochloride 15kg, water 16.9kg, CaCl
260kg, HCl 0.5kg), Oxytetracycline Base BP (98) 250kg(is water 20kg wherein, and impurity is a small amount of), acid alcohol 15.1kg is warming up to 50 ℃ in dissolving tank, be stirred to dissolving fully.Add the 780kg gac, continue to stir 30 minutes, filter with plate-and-frame filter press, gained filtrate is sent into board-like membrane separation unit, 90 ℃ of solution temperatures, carries out process of pervaporation behind the film under the absolute pressure 5kpa, separates water outlet 20kg, methyl alcohol 240kg.After pervaporation gained refined liquid is added an amount of acid alcohol, under-5 ℃, carry out freezing and crystallizing.The gained crystallization separates with separating centrifuge, and wet crystallization drying gets tetramycin hydrochloride 240kg, and the mother liquid obtained 1200kg of centrifugation is for reusing.
Embodiment 2: get mother liquor 2000kg, the wherein moisture 32kg of Oxytetracycline Base BP (98) 400kg(), acid alcohol 25kg, in dissolving tank, be warming up to 50 ℃, be stirred to dissolving fully, add gac 1500g, continue to stir 30 minutes, filter in pressure filter, gained filtrate is sent into membrane separation unit.70 ℃ of solution temperatures, carry out the infiltration evaporation process behind the film under the absolute pressure 1kpa.Separate water outlet 32kg, methyl alcohol 60kg after refined liquid is added an amount of acid alcohol, carries out freezing and crystallizing under 0 ℃, centrifugation subsequently, and the crystallization of must wetting, drying gets tetramycin hydrochloride 390kg, and the mother liquid obtained 2000kg altogether of centrifugation is for reusing.
Embodiment 3: get mother liquor 1200kg(and wherein contain methyl alcohol 1110kg, tetramycin hydrochloride 22.5kg, water 7kg, CaCl
260kg, HCl 0.5kg), Oxytetracycline Base BP (98) 240kg(is water 19kg wherein) and, acid alcohol 14.5kg is warming up to 50 ℃ in dissolving tank, be stirred to dissolving fully.Add the 750g gac, continue to stir 30 minutes, mixed solution filters, and filtrate is added the laggard capable freezing and crystallizing of an amount of acid alcohol.The crystallization of must wetting of centrifugation subsequently, drying gets tetramycin hydrochloride 230kg.Centrifugation gained filtrate (mother liquor) is sent into membrane separation unit, 80 ℃ of solution temperatures, carries out pervaporation behind the film under the absolute pressure 3KPa, separates water outlet 19kg, methyl alcohol 40kg.Pervaporation gained refined liquid is directly returned dissolving tank, uses for the dissolving raw material Oxytetracycline Base BP (98).
Claims (2)
1, a kind of novel process of making tetramycin hydrochloride is characterized in that manufacturing processed is made up of following each step:
(1) Oxytetracycline Base BP (98) is dissolved with mother liquor, add acid alcohol again, the solution composition of making is: methyl alcohol 76～78%, terramycin 16～18%, water 2～3%, CaCl
2～4%, HCl～0.5%;
(2) use activated carbon decolorizing, the add-on of gac is 0.1～0.5% of a terramycin alkali number;
(3) above-mentioned mixed solution is filtered clear liquid, isolate wherein portion water with the pervaporation membrane separation unit, its operating parameters is 70 ℃～90 ℃ of temperature, absolute pressure 1～10KPa behind the film;
(4) in the refined liquid in above-mentioned the 3rd step, add acid alcohol, under 0 ℃～10 ℃, carry out freezing and crystallizing;
(5) with above-mentioned tetramycin hydrochloride crystallization through the centrifugation crystallization of must wetting, drying gets the tetramycin hydrochloride finished product again, isolating mother liquor returns dissolving tank, uses for the dissolving raw material Oxytetracycline Base BP (98).
2, a kind of novel process of making tetramycin hydrochloride is characterized in that manufacturing processed is made up of following each step:
(1) Oxytetracycline Base BP (98) is dissolved with mother liquor, add acid alcohol again, the solution composition of making is: methyl alcohol 76～78%, terramycin 16～18%, water 2～3%, CaCl
2～4%, HCl～0.5%;
(2) use activated carbon decolorizing, the add-on of gac is 0.1～0.5% of a terramycin alkali number;
(3) in the solution in above-mentioned second step, add acid alcohol, on 0 ℃～10 ℃, carry out freezing and crystallizing;
(4) with above-mentioned tetramycin hydrochloride crystallization through the centrifugation crystallization of must wetting, drying gets the tetramycin hydrochloride finished product again; (5) centrifugation gained filtrate is isolated wherein portion water with the pervaporation membrane separation unit, its operating parameters is 70 ℃～90 ℃ of temperature, absolute pressure 1～10KPa behind the film, and the refined liquid of pervaporation is returned dissolving tank, uses for the dissolving raw material Oxytetracycline Base BP (98).
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN93114290A CN1039412C (en) | 1993-11-12 | 1993-11-12 | Production of oxytetracycline hydrochloride |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN93114290A CN1039412C (en) | 1993-11-12 | 1993-11-12 | Production of oxytetracycline hydrochloride |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN1090268A true CN1090268A (en) | 1994-08-03 |
| CN1039412C CN1039412C (en) | 1998-08-05 |
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN93114290A Expired - Fee Related CN1039412C (en) | 1993-11-12 | 1993-11-12 | Production of oxytetracycline hydrochloride |
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| Country | Link |
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| CN (1) | CN1039412C (en) |
Cited By (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101570495A (en) * | 2008-04-28 | 2009-11-04 | 大丰华曙药业有限公司 | Production process of oxytetracycline dihydrate hydrochloride |
| CN101811979A (en) * | 2010-04-29 | 2010-08-25 | 赤峰制药股份有限公司 | Technology for producing injection-grade terramycin |
| CN101823980A (en) * | 2010-04-29 | 2010-09-08 | 赤峰制药股份有限公司 | Preparation method of large-grain occrycetin |
| CN101914035A (en) * | 2010-08-27 | 2010-12-15 | 扬州联博药业有限公司 | Method for preparing oxytetracycline hydrochloride |
| CN102816084A (en) * | 2012-09-10 | 2012-12-12 | 赤峰奥贝思医药科技有限责任公司 | Method for preparing injection-grade oxytetracycline |
| 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 |
| CN108586277A (en) * | 2018-05-29 | 2018-09-28 | 江西国药有限责任公司 | A kind of preparation method of occrycetin fine grained salt |
| CN112624937A (en) * | 2020-12-23 | 2021-04-09 | 江苏天和制药有限公司 | Drying method of oxytetracycline hydrochloride |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US507595A (en) * | 1893-10-31 | Ville |
-
1993
- 1993-11-12 CN CN93114290A patent/CN1039412C/en not_active Expired - Fee Related
Cited By (15)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101570495A (en) * | 2008-04-28 | 2009-11-04 | 大丰华曙药业有限公司 | Production process of oxytetracycline dihydrate hydrochloride |
| CN101823980B (en) * | 2010-04-29 | 2013-09-18 | 赤峰制药股份有限公司 | Preparation method of large-grain occrycetin |
| CN101811979A (en) * | 2010-04-29 | 2010-08-25 | 赤峰制药股份有限公司 | Technology for producing injection-grade terramycin |
| CN101823980A (en) * | 2010-04-29 | 2010-09-08 | 赤峰制药股份有限公司 | Preparation method of large-grain occrycetin |
| CN101811979B (en) * | 2010-04-29 | 2012-10-31 | 赤峰制药股份有限公司 | Technology for producing injection-grade terramycin |
| CN101914035A (en) * | 2010-08-27 | 2010-12-15 | 扬州联博药业有限公司 | Method for preparing oxytetracycline hydrochloride |
| CN101914035B (en) * | 2010-08-27 | 2014-03-05 | 扬州联博药业有限公司 | Method for preparing oxytetracycline hydrochloride |
| CN102816084A (en) * | 2012-09-10 | 2012-12-12 | 赤峰奥贝思医药科技有限责任公司 | Method for preparing injection-grade oxytetracycline |
| CN102816084B (en) * | 2012-09-10 | 2015-02-04 | 赤峰奥贝思医药科技有限责任公司 | Method for preparing injection-grade oxytetracycline |
| 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 |
| CN107011205B (en) * | 2017-04-12 | 2019-10-01 | 扬州联博药业有限公司 | A method of 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 |
| CN108586277A (en) * | 2018-05-29 | 2018-09-28 | 江西国药有限责任公司 | A kind of preparation method of occrycetin fine grained salt |
| CN108586277B (en) * | 2018-05-29 | 2020-12-04 | 江西国药有限责任公司 | Preparation method of oxytetracycline hydrochloride fine particle salt |
| CN112624937A (en) * | 2020-12-23 | 2021-04-09 | 江苏天和制药有限公司 | Drying method of oxytetracycline hydrochloride |
Also Published As
| Publication number | Publication date |
|---|---|
| CN1039412C (en) | 1998-08-05 |
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