CN106946728B - A method of producing Doxycycline monohydrate - Google Patents
A method of producing Doxycycline monohydrate Download PDFInfo
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- CN106946728B CN106946728B CN201710237264.2A CN201710237264A CN106946728B CN 106946728 B CN106946728 B CN 106946728B CN 201710237264 A CN201710237264 A CN 201710237264A CN 106946728 B CN106946728 B CN 106946728B
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- doxycycline
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- 229960004434 doxycycline monohydrate Drugs 0.000 title claims abstract description 17
- XQTWDDCIUJNLTR-CVHRZJFOSA-N doxycycline monohydrate Chemical compound O.O=C1C2=C(O)C=CC=C2[C@H](C)[C@@H]2C1=C(O)[C@]1(O)C(=O)C(C(N)=O)=C(O)[C@@H](N(C)C)[C@@H]1[C@H]2O XQTWDDCIUJNLTR-CVHRZJFOSA-N 0.000 title claims abstract 11
- 238000000034 method Methods 0.000 title abstract description 13
- 239000000047 product Substances 0.000 claims abstract description 39
- 239000003513 alkali Substances 0.000 claims abstract description 27
- 150000003839 salts Chemical class 0.000 claims abstract description 24
- 229960003722 doxycycline Drugs 0.000 claims abstract description 23
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 12
- 238000004519 manufacturing process Methods 0.000 claims abstract description 9
- 239000012043 crude product Substances 0.000 claims abstract description 8
- WXHLLJAMBQLULT-UHFFFAOYSA-N 2-[[6-[4-(2-hydroxyethyl)piperazin-1-yl]-2-methylpyrimidin-4-yl]amino]-n-(2-methyl-6-sulfanylphenyl)-1,3-thiazole-5-carboxamide;hydrate Chemical compound O.C=1C(N2CCN(CCO)CC2)=NC(C)=NC=1NC(S1)=NC=C1C(=O)NC1=C(C)C=CC=C1S WXHLLJAMBQLULT-UHFFFAOYSA-N 0.000 claims abstract description 7
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 29
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 claims description 24
- 239000000908 ammonium hydroxide Substances 0.000 claims description 24
- 150000001875 compounds Chemical class 0.000 claims description 23
- 238000003756 stirring Methods 0.000 claims description 16
- 238000001914 filtration Methods 0.000 claims description 14
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 10
- 238000005352 clarification Methods 0.000 claims description 10
- 239000000706 filtrate Substances 0.000 claims description 10
- IDGUHHHQCWSQLU-UHFFFAOYSA-N ethanol;hydrate Chemical compound O.CCO IDGUHHHQCWSQLU-UHFFFAOYSA-N 0.000 claims description 8
- 239000003643 water by type Substances 0.000 claims description 6
- 239000000463 material Substances 0.000 claims description 5
- 238000010792 warming Methods 0.000 claims description 5
- 238000004321 preservation Methods 0.000 claims description 3
- 238000001816 cooling Methods 0.000 claims description 2
- -1 doxycycline 5-sulphosalicylic acid salt Chemical class 0.000 claims description 2
- 238000005516 engineering process Methods 0.000 abstract description 2
- 238000009776 industrial production Methods 0.000 abstract description 2
- FZKWRPSUNUOXKJ-CVHRZJFOSA-N (4s,4ar,5s,5ar,6r,12ar)-4-(dimethylamino)-1,5,10,11,12a-pentahydroxy-6-methyl-3,12-dioxo-4a,5,5a,6-tetrahydro-4h-tetracene-2-carboxamide;hydrate Chemical compound O.C1=CC=C2[C@H](C)[C@@H]([C@H](O)[C@@H]3[C@](C(O)=C(C(N)=O)C(=O)[C@H]3N(C)C)(O)C3=O)C3=C(O)C2=C1O FZKWRPSUNUOXKJ-CVHRZJFOSA-N 0.000 description 17
- 235000019441 ethanol Nutrition 0.000 description 10
- HALQELOKLVRWRI-VDBOFHIQSA-N doxycycline hyclate Chemical compound O.[Cl-].[Cl-].CCO.O=C1C2=C(O)C=CC=C2[C@H](C)[C@@H]2C1=C(O)[C@]1(O)C(=O)C(C(N)=O)=C(O)[C@@H]([NH+](C)C)[C@@H]1[C@H]2O.O=C1C2=C(O)C=CC=C2[C@H](C)[C@@H]2C1=C(O)[C@]1(O)C(=O)C(C(N)=O)=C(O)[C@@H]([NH+](C)C)[C@@H]1[C@H]2O HALQELOKLVRWRI-VDBOFHIQSA-N 0.000 description 7
- 229960001172 doxycycline hyclate Drugs 0.000 description 7
- 238000007599 discharging Methods 0.000 description 6
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 4
- 238000001035 drying Methods 0.000 description 4
- 238000000926 separation method Methods 0.000 description 4
- 239000002253 acid Substances 0.000 description 3
- 229940079593 drug Drugs 0.000 description 3
- 239000003814 drug Substances 0.000 description 3
- 238000001556 precipitation Methods 0.000 description 3
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 2
- 239000005864 Sulphur Substances 0.000 description 2
- 229910021529 ammonia Inorganic materials 0.000 description 2
- 239000002585 base Substances 0.000 description 2
- 238000002360 preparation method Methods 0.000 description 2
- YGSDEFSMJLZEOE-UHFFFAOYSA-N salicylic acid Chemical compound OC(=O)C1=CC=CC=C1O YGSDEFSMJLZEOE-UHFFFAOYSA-N 0.000 description 2
- OWFJMIVZYSDULZ-PXOLEDIWSA-N (4s,4ar,5s,5ar,6s,12ar)-4-(dimethylamino)-1,5,6,10,11,12a-hexahydroxy-6-methyl-3,12-dioxo-4,4a,5,5a-tetrahydrotetracene-2-carboxamide Chemical compound C1=CC=C2[C@](O)(C)[C@H]3[C@H](O)[C@H]4[C@H](N(C)C)C(=O)C(C(N)=O)=C(O)[C@@]4(O)C(=O)C3=C(O)C2=C1O OWFJMIVZYSDULZ-PXOLEDIWSA-N 0.000 description 1
- YCPXWRQRBFJBPZ-UHFFFAOYSA-N 5-sulfosalicylic acid Chemical class OC(=O)C1=CC(S(O)(=O)=O)=CC=C1O YCPXWRQRBFJBPZ-UHFFFAOYSA-N 0.000 description 1
- 241000894006 Bacteria Species 0.000 description 1
- 241000606161 Chlamydia Species 0.000 description 1
- 241000192125 Firmicutes Species 0.000 description 1
- 206010035664 Pneumonia Diseases 0.000 description 1
- 206010057190 Respiratory tract infections Diseases 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- 210000003445 biliary tract Anatomy 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 230000000857 drug effect Effects 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 238000011835 investigation Methods 0.000 description 1
- JEIPFZHSYJVQDO-UHFFFAOYSA-N iron(III) oxide Inorganic materials O=[Fe]O[Fe]=O JEIPFZHSYJVQDO-UHFFFAOYSA-N 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- FJKROLUGYXJWQN-UHFFFAOYSA-N papa-hydroxy-benzoic acid Natural products OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 229960004889 salicylic acid Drugs 0.000 description 1
- 239000002689 soil Substances 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 229940072172 tetracycline antibiotic Drugs 0.000 description 1
- 206010044008 tonsillitis Diseases 0.000 description 1
Classifications
-
- 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
-
- 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
- C07C303/00—Preparation of esters or amides of sulfuric acids; Preparation of sulfonic acids or of their esters, halides, anhydrides or amides
- C07C303/32—Preparation of esters or amides of sulfuric acids; Preparation of sulfonic acids or of their esters, halides, anhydrides or amides of salts of sulfonic acids
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention discloses a kind of methods for producing Doxycycline monohydrate, it include: α -6- doxycycline 5-sulphosalicylic acid salt crude product by alkalization generation α -6- doxycycline alkali, gained α -6- doxycycline alkali and sulfosalicylic acid are carried out into salt, gained carries out a basification at salt object again, can obtain the one water object of Doxycycline of high-purity.The process of Doxycycline monohydrate disclosed by the invention, improves the purity of Doxycycline, up to 96% or more, can get more good finished product.It since this method is directly improved on the basis of existing production technology, can directly apply to industrial production, there is good practicability.
Description
Technical field
The invention belongs to technical field of compound preparation, and in particular to a method of produce Doxycycline monohydrate.
Background technique
The structural formula of one water object of Doxycycline is as follows:
Using Doxycycline as parent, most commonly seen drug is Doxycycline Hyclate, and the molecular formula of Doxycycline Hyclate is such as
Under:
Doxycycline Hyclate is a kind of semi-synthetic tetracycline antibiotics of wide spectrum, to gram-positive bacteria, Gram-negative
Bacterium and Chlamydia are effective, are clinically used for the prevention and treatment of respiratory tract infection, infection of biliary tract, tonsillitis, Eaton agent pneumonia.Mesh
The preparation of preceding Doxycycline Hyclate generates α -6- by alkalization as starting material using α -6- doxycycline sulfosalicylate and takes off
Oxygen Oxytetracycline Base, last acid adding generate Doxycycline Hyclate at salt.Doxycycline Hyclate is because of good water solubility, good fluidity, more
It is easy to be absorbed by way of oral, therefore very extensive in clinical application.But recently as people to the rouge of drug
Dissolubility and water-soluble further investigation, finding fat-soluble drug also has their specific drug effects, therefore emerges a batch now
Demand of the client to Doxycycline monohydrate, actually during preparing Doxycycline Hyclate, the intermediate α-of generation
6- doxycycline alkali is exactly the crude product (purity only have about 75%) of Doxycycline monohydrate, but for how purifying or
Say that the research for how preparing the one water object of Doxycycline of high-purity (96% or more) is relatively fewer.
Summary of the invention
In order to overcome the defects of the prior art described above, the present invention provides a kind of production high-purity Doxycycline monohydrates
Method, purity reaches 96% or more.
In order to solve the above-mentioned technical problem, the technical solution adopted by the present invention is that:
A method of Doxycycline monohydrate is produced, is included the following steps:
1) α -6- doxycycline 5-sulphosalicylic acid salt crude product is added to 15~20 DEG C of 70~75% ethanol waters
In, it stirring and ammonium hydroxide is added dropwise to solution dissolved clarification, control temperature is no more than 20 DEG C, and filtrate is heated to 40 ~ 45 DEG C, kept the temperature by filtering,
20 ~ 25 DEG C are cooled to, first time alkali compound tide product are obtained by filtration；
2) the damp product of gained in step 1) are added in 55 ~ 60% ethanol waters, hydrochloric acid tune pH to 3 ~ 3.5 is added, continues
50 ~ 55 DEG C are warming up to, material is dissolved all, sulfosalicylic acid is then added, stirs, 20 ~ 25 DEG C is naturally cooling to, at salt object
It is precipitated, salt object tide product is obtained by filtration into；
3) it is added in 10 ~ 15 DEG C of 70~75% ethanol waters at salt object tide product by step 2 is resulting, is sufficiently stirred
Afterwards, starting to be added dropwise ammonium hydroxide to solution dissolved clarification, control temperature is no more than 18 DEG C, and filtrate is heated to 40 ~ 45 DEG C, kept the temperature by filtering, from
10 ~ 15 DEG C so are cooled to, alkali compound tide product are obtained by filtration；
4) the alkali compound tide product of step 3) are dry by vacuum oven, obtain one water object finished product of Doxycycline.
In step 1), the mass volume ratio of α -6- doxycycline 5-sulphosalicylic acid salt crude product and ethanol water is 1:
2 ~ 3, the mass concentration of ammonium hydroxide is 20 ~ 25%.
In step 2, the mass volume ratio of first time alkali compound and ethanol water is 1:3 ~ 4, first time alkali compound and sulphur
The salicylic mass ratio of base is 1:1.0 ~ 1.5, and the concentration of hydrochloric acid is 10 ~ 15%.
It is once 1:3 ~ 4 at the mass volume ratio of salt object and ethanol water, the mass concentration of ammonium hydroxide is 20 in step 3)
~25%。
In step 4), drying temperature is 70 ~ 80 DEG C.
The utility model has the advantages that compared with prior art, the method for production Doxycycline monohydrate of the invention, α -6- deoxidation soil
Mycin 5-sulphosalicylic acid salt crude product generates α -6- doxycycline alkali by alkalization, by gained α -6- doxycycline alkali and sulphur
Base salicylic acid is carried out into salt, and gained carries out a basification at salt object again, can obtain Doxycycline one water of the purity 96% or more
Object can directly apply to industrial production since this method is directly improved on the basis of existing production technology, have good
Practicability.
Specific embodiment
The present invention is described further combined with specific embodiments below.
Embodiment 1
A method of Doxycycline monohydrate being produced, steps are as follows:
1) 100g is hydrogenated to salt object (α -6- doxycycline 5-sulphosalicylic acid salt crude product) and is added to 200mL, 15 DEG C
70%(v/v) ethanol water in, after stirring 10min, start that ammonium hydroxide is added dropwise, when pH value reaches 5.8, stop that ammonium hydroxide is added dropwise,
Temperature is 18 DEG C at this time, stirs 10min, until filtrate is heated to 45 DEG C, keeps the temperature 30min, be cooled to by alkali compound dissolved clarification, filtering
25 DEG C of dischargings, centrifuge separation obtain first time alkali compound tide product 65g.
2) the damp product 60g for taking step 1), is added to 180mL, 60%(v/v) ethanol water in, 10% hydrochloric acid is added
PH to 3.5 is adjusted, is warming up to 55 DEG C, so that material all dissolves, 60g sulfosalicylic acid is then added, stirs 10min, it is rear to drop
Temperature is secondary to be precipitated at salt object to 25 DEG C, and centrifuge separation obtains secondary at salt object tide product 85g.
3) take the damp product 80g that step 2 obtains, be added to the 70%(v/v of 240mL, 15 DEG C) ethyl alcohol in, be sufficiently stirred
After 30min, start dropwise addition ammonium hydroxide, during ammonium hydroxide is added dropwise in control, temperature is no more than 18 DEG C, and when pH value reaches 6.0, stopping is dripped
After adding ammonium hydroxide, ammonium hydroxide to be added dropwise to complete, temperature is 6 DEG C, stirs 10min, until alkali compound dissolved clarification, filtering, are heated to 45 DEG C for filtrate,
30min is kept the temperature, product precipitation is cooled to, is cooled to 15 DEG C of dischargings, be centrifugated, obtain second of alkali compound tide product 50g.
4) by the damp product of step 3) by vacuum oven, the drying at 0.08MPa, 70 degree obtains one water of Doxycycline
Close object finished product 42g, purity 98.8%.
Embodiment 2
A method of Doxycycline monohydrate being produced, steps are as follows:
1) 100g is hydrogenated to salt object and is added to 200mL, in 19 DEG C of 75% ethyl alcohol, after stirring 10min, start to be added dropwise
Ammonium hydroxide, when pH value reaches 5.8, ammonium hydroxide is added dropwise in stopping, and temperature is 15 DEG C at this time, stirs 10min, until alkali compound dissolved clarification, is filtered, by
Filtrate is heated to 45 DEG C, keeps the temperature 30min, is cooled to 25 DEG C of dischargings, is centrifugated, obtains first time alkali compound tide product 62g.
2) the damp product 60g for taking step 1), is added to 180mL, in 60% ethyl alcohol, 10% salt acid for adjusting pH is added to 3.5,
Be warming up to 55 DEG C, so that material all dissolves, 68g sulfosalicylic acid be then added, stirs 10min, after be cooled to 25 DEG C, it is secondary
It is precipitated at salt object, centrifuge separation obtains secondary at salt object tide product 83g.
3) the damp product 80g that step 2 obtains is taken, is added to 240mL, in 19 DEG C of 75% ethyl alcohol, 30min is sufficiently stirred
Afterwards, start that ammonium hydroxide is added dropwise, during ammonium hydroxide is added dropwise in control, temperature is no more than 15 DEG C, and when pH value reaches 6.0, ammonia is added dropwise in stopping
Water, after ammonium hydroxide is added dropwise to complete, temperature is 6 DEG C, stirs 10min, until filtrate is heated to 45 DEG C, heat preservation by alkali compound dissolved clarification, filtering
30min is cooled to product precipitation, is cooled to 15 DEG C of dischargings, is centrifugated, obtains second of alkali compound tide product 50g.
4) by the damp product of step 3) by vacuum oven, the drying at 0.08MPa, 70 degree obtains one water of Doxycycline
Close object finished product 43g.Purity is 99.2%.
Embodiment 3
A method of Doxycycline monohydrate being produced, steps are as follows:
1) 100g is hydrogenated to salt object and is added to 200mL, in 12 DEG C of 70% ethyl alcohol, after stirring 10min, start to be added dropwise
Ammonium hydroxide, when pH value reaches 5.8, ammonium hydroxide is added dropwise in stopping, and temperature is 10 DEG C at this time, stirs 10min, until alkali compound dissolved clarification, is filtered, by
Filtrate is heated to 45 DEG C, keeps the temperature 30min, is cooled to 25 DEG C of dischargings, is centrifugated, obtains first time alkali compound tide product 56g.
2) the damp product 50g for taking step 1), is added to 180mL, in 60% ethyl alcohol, 10% salt acid for adjusting pH is added to 3.5,
Be warming up to 55 DEG C, so that material all dissolves, 70g sulfosalicylic acid be then added, stirs 10min, after be cooled to 25 DEG C, it is secondary
It is precipitated at salt object, centrifuge separation obtains secondary at salt object tide product 65g.
3) the damp product 60g that step 2 obtains is taken, 240mL is added to, in 12 DEG C of 70% ethyl alcohol, 30min is sufficiently stirred
Afterwards, start that ammonium hydroxide is added dropwise, during ammonium hydroxide is added dropwise in control, temperature is no more than 10 DEG C, and when pH value reaches 6.0, ammonia is added dropwise in stopping
Water, after ammonium hydroxide is added dropwise to complete, temperature is 6 DEG C, stirs 10min, until filtrate is heated to 45 DEG C, heat preservation by alkali compound dissolved clarification, filtering
30min is cooled to product precipitation, is cooled to 15 DEG C of dischargings, is centrifugated, obtains second of alkali compound tide product 35.8g.
4) by the damp product of step 3) by vacuum oven, the drying at 0.08MPa, 70 degree obtains one water of Doxycycline
Close object finished product 39g, purity 98.5%.
Claims (5)
1. a kind of method for producing Doxycycline monohydrate, which comprises the steps of:
1) α -6- doxycycline 5-sulphosalicylic acid salt crude product is added in 15~20 DEG C of 70~75% ethanol waters,
It stirs and ammonium hydroxide is added dropwise to solution dissolved clarification, control temperature and be no more than 20 DEG C, filtrate is heated to 40~45 DEG C by filtering, and heat preservation is cold
But to 20~25 DEG C, first time alkali compound tide product are obtained by filtration；
2) the damp product of gained in step 1) are added in 55~60% ethanol waters, hydrochloric acid tune pH to 3~3.5 is added, continues
50~55 DEG C are warming up to, material is dissolved all, sulfosalicylic acid is then added, stirs, 20~25 DEG C is naturally cooling to, at salt
Object is precipitated, and salt object tide product are obtained by filtration into；
3) it is added in 10~15 DEG C of 70~75% ethanol waters at salt object tide product by step 2) is resulting, is sufficiently stirred
Afterwards, starting to be added dropwise ammonium hydroxide to solution dissolved clarification, control temperature is no more than 18 DEG C, and filtrate is heated to 40~45 DEG C, kept the temperature by filtering,
10~15 DEG C are naturally cooled to, alkali compound tide product are obtained by filtration；
4) the alkali compound tide product of step 3) are dry by vacuum oven, obtain one water object finished product of Doxycycline.
2. the method for production Doxycycline monohydrate according to claim 1, which is characterized in that in step 1), α -6-
The mass volume ratio g/mL of doxycycline 5-sulphosalicylic acid salt crude product and ethanol water is 1:2~3, and the quality of ammonium hydroxide is dense
Degree is 20~25%.
3. the method for production Doxycycline monohydrate according to claim 1, which is characterized in that in step 2), first
The mass volume ratio g/mL of secondary alkali compound and ethanol water is 1:3~4, the mass ratio of first time alkali compound and sulfosalicylic acid
For 1:1.0~1.5, the concentration of hydrochloric acid is 10~15%.
4. the method for production Doxycycline monohydrate according to claim 1, which is characterized in that in step 3), once
It is 1:3~4 at the mass volume ratio g/mL of salt object and ethanol water, the mass concentration of ammonium hydroxide is 20~25%.
5. the method for production Doxycycline monohydrate according to claim 1, which is characterized in that dry in step 4)
Temperature is 70~80 DEG C.
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| CN201710237264.2A CN106946728B (en) | 2017-04-12 | 2017-04-12 | A method of producing Doxycycline monohydrate |
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| CN113264846B (en) * | 2021-04-25 | 2022-08-26 | 镇江高海生物药业有限公司 | Preparation method of doxycycline monohydrate |
| CN118724355A (en) * | 2024-07-18 | 2024-10-01 | 扬州联博药业有限公司 | A method for treating and recycling ammonia nitrogen in doxycycline hydrochloride production wastewater |
Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0086046A1 (en) * | 1982-01-19 | 1983-08-17 | Plurichemie Anstalt | A process for the preparation of alpha-6-DEOXYTETRACYCLINES |
| US5049683A (en) * | 1989-01-04 | 1991-09-17 | Houba, Inc. | Process for the production of alpha-6-deoxytetracyclines |
| CN101209978A (en) * | 2006-12-25 | 2008-07-02 | 林广德 | Method for synthesizing dexocycline hydrochloridele from 6-methyl terramycin salt of organic acid |
| CN101786971A (en) * | 2010-03-01 | 2010-07-28 | 扬州联博药业有限公司 | Preparation process of doxycycline hydrochloride |
| CN105924367A (en) * | 2016-04-18 | 2016-09-07 | 镇江高海生物药业有限公司 | Substance related to doxycycline monohydrate as well as analysis and detection method thereof |
-
2017
- 2017-04-12 CN CN201710237264.2A patent/CN106946728B/en active Active
Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0086046A1 (en) * | 1982-01-19 | 1983-08-17 | Plurichemie Anstalt | A process for the preparation of alpha-6-DEOXYTETRACYCLINES |
| US5049683A (en) * | 1989-01-04 | 1991-09-17 | Houba, Inc. | Process for the production of alpha-6-deoxytetracyclines |
| CN101209978A (en) * | 2006-12-25 | 2008-07-02 | 林广德 | Method for synthesizing dexocycline hydrochloridele from 6-methyl terramycin salt of organic acid |
| CN101786971A (en) * | 2010-03-01 | 2010-07-28 | 扬州联博药业有限公司 | Preparation process of doxycycline hydrochloride |
| CN105924367A (en) * | 2016-04-18 | 2016-09-07 | 镇江高海生物药业有限公司 | Substance related to doxycycline monohydrate as well as analysis and detection method thereof |
Non-Patent Citations (6)
| Title |
|---|
| Solid state chemistry of the antibiotic doxycycline: structure of the neutral monohydrate and insights into its poor water solubility;Alexandre O.Legendre 等;《CrystEngComm》;20111201;第14卷(第7期);第2532-2540页 |
| Solubility of doxycycline in aqueous solution;Bogardus,Joseph B. 等;《Journal of Pharmaceutical Sciences》;19790228;第68卷(第2期);第188-194页 |
| 强力霉素碱先精制后成盐操作工艺;刘庆荣;《医药工业》;19790730(第7期);第10-11页 |
| 盐酸多西环素的合成工艺研究;张红东;《中国医药指南》;20101020;第8卷(第29期);第43-44页 |
| 盐酸多西环素精制母液物料的回收及提纯;胡汉峰;《化工技术与开发》;20041030;第33卷(第5期);第47页左栏第1段和第47-48页图解 |
| 盐酸多西环素精制结晶工艺的改进;刘益华;《齐鲁药事》;20040429;第23卷(第2期);第54-55页 |
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