CN108586277A - A kind of preparation method of occrycetin fine grained salt - Google Patents
A kind of preparation method of occrycetin fine grained salt Download PDFInfo
- Publication number
- CN108586277A CN108586277A CN201810526138.3A CN201810526138A CN108586277A CN 108586277 A CN108586277 A CN 108586277A CN 201810526138 A CN201810526138 A CN 201810526138A CN 108586277 A CN108586277 A CN 108586277A
- Authority
- CN
- China
- Prior art keywords
- occrycetin
- terramycin
- fine grained
- ethyl alcohol
- salt
- Prior art date
- 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.)
- Granted
Links
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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/65—Tetracyclines
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
-
- 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
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Epidemiology (AREA)
- Communicable Diseases (AREA)
- Oncology (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Medicinal Preparation (AREA)
- Agricultural Chemicals And Associated Chemicals (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention discloses a kind of preparation methods of occrycetin fine grained salt, specifically there is pre- water removal, at salt, bonding, drying and other steps, it is cleaned in advance using zeolite powder in pre- the step of removing water first, then it is decolourized and is cleaned using compound resin before at salt, finally select povidone k30 etc. to be used as adhesive and adhesion promoter, not only yield and purity are high for occrycetin fine grained salt obtained, and good decolorizing effect, granularity meets production requirement, good fluidity, bulk density height.
Description
Technical field
The present invention relates to a kind of preparation of antibiotic, more particularly to a kind of preparation method of occrycetin fine grained salt.
Background technology
Occrycetin, also known as Terramycin hydrochloride, Oxytetracycline Hydrochloride, oxytetracycline hydrochloride are that a kind of humans and animals are wide
The general antibiotic used is clinically used for treating a variety of diseases, such as Li Kecishi diseases, including epidemic typhus, region spot
Rash typhoid fever, yochubio；Infection caused by mycoplasma pneumoniae；Choamydiae infection, including it is psittacosis, lymphogranuloma granuloma, non-specific
Property urethritis, salpingitis and trachoma；Relapsing fever；Brucellosis；Cholera；The plague and yatobyo etc..Occrycetin clinic makes
Dosage form has tablet, capsule, pulvis, eye drops and ointment etc..
Most of current market sales of occrycetin is tiny monocrystal powder, and poor fluidity, granularity is small, raw
During producing use, when being mixed with other materials, it is susceptible to mixing non-uniform phenomenon, inconvenience is brought to production.
Invention content
The object of the present invention is to provide a kind of preparation method of occrycetin fine grained salt, specifically there is pre- water removal, at salt, viscous
It closes, drying and other steps, is cleaned in advance using zeolite powder in pre- the step of removing water first, compound tree is then used before at salt
Fat is decolourized and is cleaned, and finally povidone k30 etc. is selected to be used as adhesive and adhesion promoter, occrycetin fine grained salt obtained
Not only yield and purity are high, but also good decolorizing effect, meet production requirement, good fluidity, bulk density height.
A kind of preparation method of occrycetin fine grained salt, includes the following steps：
(1) pre- water removal：Terramycin raw material and ethyl alcohol are put into the first reaction kettle, heating distills out 1/2-2/3 volumes
Ethyl alcohol is cooled to room temperature, then material in the first reaction kettle is centrifuged, and obtains the terramycin wet product that water content is less than 0.1%；
(2) at salt：Calcium chloride and methanol are put into the second reaction kettle, stirring and dissolving obtains calcium chloride methanol solution, then to
The terramycin wet product that step (1) obtains, stirring are added in second reaction kettle, 30-40 DEG C of low-grade fever is all dissolved to terramycin wet product
Afterwards, add compound resin, stir, filtering obtains terramycin methanol solution, after terramycin methanol solution is cooled to room temperature, adds
Hydrogen chloride methanol solution, stirred crystallization are cooled to 5 DEG C, and filtering obtains occrycetin wet product and mother liquor, and mother liquor is sent into fluid reservoir；
(3) it bonds：By occrycetin wet product, acetone, ethyl alcohol, water, povidone k30, cationic polyacrylamide, sweet dew
Alcohol mixes according to the ratio, is uniformly mixed, is heated to 35-40 DEG C, obtains occrycetin powder；
(4) dry：The occrycetin powder that step (3) obtains is carried out under conditions of vacuum degree≤- 0.090mpa
It is dry, obtain occrycetin fine grained salt finished product.
In the step (1), the solid-liquid ratio of terramycin raw material and ethyl alcohol is：1kg:2-4L.
In the step (1), the zeolite powder after activation, the addition of zeolite powder are added in the material being cooled to room temperature
Amount is the 1-3% of terramycin material quality.
Wherein, the activation step of zeolite powder is：Zeolite powder, ethyl alcohol, acetone are uniformly mixed, are heated to 50 DEG C, is filtered, boiling
Mountain flour, ethyl alcohol, acetone proportioning be：1g:10-20ml:10ml.
In the step (2), the solid-liquid ratio of terramycin raw material and methanol is：1kg:3.5-4.5L.
In the step (2), the mass ratio of terramycin raw material and calcium chloride is：1:0.1-0.2.
In the step (2), the dosage of compound resin is the 0.5-1.5% of terramycin material quality.
Wherein, compound resin is made of the raw material of following quality proportioning：5-10 parts of X-5 macroporous absorbent resins, D3520 macropores
Adsorb 1-3 parts of resin, 1-3 parts of DA-201 macroporous absorbent resins.
In the step (2), the solid-liquid ratio of terramycin raw material and hydrogen chloride methanol solution is：
1kg:0.3-0.5L。
In the step (3), occrycetin wet product, acetone, ethyl alcohol, water, povidone k30, cation polypropylene
Amide, mannitol mass ratio be：
10:1.05-1.25:2.25-2.45:1:1:0.7-0.9:0.45-0.55。
Hydrogen chloride methanol solution can be bought in Hubei Xin Mingtai Chemical Co., Ltd.s.
X-5 macroporous absorbent resins, D3520 macroporous absorbent resins, DA-201 macroporous absorbent resins can be in the great poly- trees in Tianjin
Fat Science and Technology Ltd. buys.
The advantage of the invention is that：
1, terramycin is removed water in advance with ethyl alcohol first, is removed using the zeolite powder after activation while pre- water removal
It is miscellaneous, the yield of occrycetin can be not only improved, the impurity of occrycetin product is also reduced.
2, before terramycin is at salt, activated carbon is replaced to be decolourized and cleaned with compound resin, decolorizing effect is substantially better than
The activated carbon used in the prior art, and further improve impurity-eliminating effect so that the purity and receipts of occrycetin product
Rate is higher.
3, select povidone k30 and cationic polyacrylamide as adhesive, acetone, ethyl alcohol, mannitol are viscous as helping
The occrycetin fine grained salt that granularity is 100-200 μm, while good fluidity, pine can be made in occrycetin wet product by agent
Density is high.
In conclusion the present invention is during preparing occrycetin fine grained salt, it is sharp in pre- the step of removing water first
It is cleaned in advance with the zeolite powder after activation, is then decolourized and cleaned using compound resin before at salt, finally selected poly-
It ties up ketone k30 and cationic polyacrylamide etc. and is used as adhesive and adhesion promoter, occrycetin fine grained salt obtained not only yield
And purity is high, and good decolorizing effect, granularity meet production requirement, good fluidity, bulk density height.
Specific implementation mode
Embodiment 1
A kind of preparation method of occrycetin fine grained salt, includes the following steps：
(1) pre- water removal：100kg terramycin raw material and 200L ethyl alcohol are put into the first reaction kettle, heating distills out 1/2-
The ethyl alcohol of 2/3 volume, is cooled to room temperature, then material in the first reaction kettle is centrifuged, and obtains the soil that water content is less than 0.1%
Mycin wet product；
(2) at salt：10kg calcium chloride and 350L methanol are put into the second reaction kettle, it is molten that stirring and dissolving obtains calcium chloride methanol
Liquid, then step (1) obtained terramycin wet product is added into the second reaction kettle, stirring, 30 DEG C of low-grade fever are whole to terramycin wet product
After dissolving, add compound resin 0.5kg, stir, filtering obtains terramycin methanol solution, waits for that terramycin methanol solution is cooled to room temperature
Afterwards, 30L hydrogen chloride methanol solutions are added, stirred crystallization is cooled to 5 DEG C, and filtering obtains occrycetin wet product and mother liquor, female
Liquid is sent into fluid reservoir；
(3) it bonds：By occrycetin wet product, acetone, ethyl alcohol, water, povidone k30, cationic polyacrylamide, sweet dew
Alcohol mixes according to the ratio, is uniformly mixed, is heated to 35 DEG C, obtains occrycetin powder；
(4) dry：The occrycetin powder that step (3) obtains is carried out under conditions of vacuum degree≤- 0.090mpa
It is dry, obtain occrycetin fine grained salt finished product.
In the step (1), the 1kg zeolite powders after activation are added in the material being cooled to room temperature.
Wherein, the activation step of zeolite powder is：Zeolite powder, ethyl alcohol, acetone are uniformly mixed, are heated to 50 DEG C, is filtered, boiling
Mountain flour, ethyl alcohol, acetone proportioning be：1g:10ml:10ml.
In the step (2), compound resin is made of the raw material of following quality proportioning：X-5 macroporous absorbent resins 5
Part, 1 part of D3520 macroporous absorbent resins, 1 part of DA-201 macroporous absorbent resins.
In the step (3), occrycetin wet product, acetone, ethyl alcohol, water, povidone k30, cation polypropylene
Amide, mannitol mass ratio be：10:1.05:2.25:1:1:0.7:0.45.
Embodiment 2
A kind of preparation method of occrycetin fine grained salt, includes the following steps：
(1) pre- water removal：100kg terramycin raw material and 300L ethyl alcohol are put into the first reaction kettle, heating distills out 2/3 body
Long-pending ethyl alcohol, is cooled to room temperature, then material in the first reaction kettle is centrifuged, and obtains the terramycin that water content is less than 0.1%
Wet product；
(2) at salt：15kg calcium chloride and 400L methanol are put into the second reaction kettle, it is molten that stirring and dissolving obtains calcium chloride methanol
Liquid, then step (1) obtained terramycin wet product is added into the second reaction kettle, stirring, 35 DEG C of low-grade fever are whole to terramycin wet product
After dissolving, adding 1kg compound resins, stirs, filtering obtains terramycin methanol solution, after terramycin methanol solution is cooled to room temperature,
40L hydrogen chloride methanol solutions are added, stirred crystallization is cooled to 5 DEG C, and filtering obtains occrycetin wet product and mother liquor, mother liquor is sent
Enter fluid reservoir；
(3) it bonds：By occrycetin wet product, acetone, ethyl alcohol, water, povidone k30, cationic polyacrylamide, sweet dew
Alcohol mixes according to the ratio, is uniformly mixed, is heated to 38 DEG C, obtains occrycetin powder；
(4) dry：The occrycetin powder that step (3) obtains is carried out under conditions of vacuum degree≤- 0.090mpa
It is dry, obtain occrycetin fine grained salt finished product.
In the step (1), the 2kg zeolite powders after activation are added in the material being cooled to room temperature.
Wherein, the activation step of zeolite powder is：Zeolite powder, ethyl alcohol, acetone are uniformly mixed, are heated to 50 DEG C, is filtered, boiling
Mountain flour, ethyl alcohol, acetone proportioning be：1g:15ml:10ml.
In the step (2), compound resin is made of the raw material of following quality proportioning：X-5 macroporous absorbent resins 8
Part, 2 parts of D3520 macroporous absorbent resins, 2 parts of DA-201 macroporous absorbent resins.
In the step (3), occrycetin wet product, acetone, ethyl alcohol, water, povidone k30, cation polypropylene
Amide, mannitol mass ratio be：10:1.15:2.35:1:1:0.8:0.50.
Embodiment 3
A kind of preparation method of occrycetin fine grained salt, includes the following steps：
(1) pre- water removal：100kg terramycin raw material and 400L ethyl alcohol are put into the first reaction kettle, heating distills out 2/3 body
Long-pending ethyl alcohol, is cooled to room temperature, then material in the first reaction kettle is centrifuged, and obtains the terramycin that water content is less than 0.1%
Wet product；
(2) at salt：20kg calcium chloride and 450L methanol are put into the second reaction kettle, it is molten that stirring and dissolving obtains calcium chloride methanol
Liquid, then step (1) obtained terramycin wet product is added into the second reaction kettle, stirring, 40 DEG C of low-grade fever are whole to terramycin wet product
After dissolving, add 1.5kg compound resins, stir, filtering obtains terramycin methanol solution, waits for that terramycin methanol solution is cooled to room temperature
Afterwards, then 50L hydrogen chloride methanol solutions, stirred crystallization, 5 DEG C are cooled to, filtering obtains occrycetin wet product and mother liquor, mother liquor is sent
Enter fluid reservoir；
(3) it bonds：By occrycetin wet product, acetone, ethyl alcohol, water, povidone k30, cationic polyacrylamide, sweet dew
Alcohol mixes according to the ratio, is uniformly mixed, is heated to 40 DEG C, obtains occrycetin powder；
(4) dry：The occrycetin powder that step (3) obtains is carried out under conditions of vacuum degree≤- 0.090mpa
It is dry, obtain occrycetin fine grained salt finished product.
In the step (1), the 3kg zeolite powders after activation are added in the material being cooled to room temperature.
Wherein, the activation step of zeolite powder is：Zeolite powder, ethyl alcohol, acetone are uniformly mixed, are heated to 50 DEG C, is filtered, boiling
Mountain flour, ethyl alcohol, acetone proportioning be：1g:20ml:10ml.
In the step (2), compound resin is made of the raw material of following quality proportioning：X-5 macroporous absorbent resins 10
Part, 3 parts of D3520 macroporous absorbent resins, 3 parts of DA-201 macroporous absorbent resins.
In the step (3), occrycetin wet product, acetone, ethyl alcohol, water, povidone k30, cation polypropylene
Amide, mannitol mass ratio be：10:1.25:2.45:1:1:0.9:0.55.
Embodiment 4
A kind of preparation method of occrycetin fine grained salt, includes the following steps：
(1) pre- water removal：100kg terramycin raw material and 250L ethyl alcohol are put into the first reaction kettle, heating distills out 1/2 body
Long-pending ethyl alcohol, is cooled to room temperature, then material in the first reaction kettle is centrifuged, and obtains the terramycin that water content is less than 0.1%
Wet product；
(2) at salt：10kg calcium chloride and 400L methanol are put into the second reaction kettle, it is molten that stirring and dissolving obtains calcium chloride methanol
Liquid, then step (1) obtained terramycin wet product is added into the second reaction kettle, stirring, 40 DEG C of low-grade fever are whole to terramycin wet product
After dissolving, add 0.5kg compound resins, stir, filtering obtains terramycin methanol solution, waits for that terramycin methanol solution is cooled to room temperature
Afterwards, 40L hydrogen chloride methanol solutions are added, stirred crystallization is cooled to 5 DEG C, and filtering obtains occrycetin wet product and mother liquor, female
Liquid is sent into fluid reservoir；
(3) it bonds：By occrycetin wet product, acetone, ethyl alcohol, water, povidone k30, cationic polyacrylamide, sweet dew
Alcohol mixes according to the ratio, is uniformly mixed, is heated to 38 DEG C, obtains occrycetin powder；
(4) dry：The occrycetin powder that step (3) obtains is carried out under conditions of vacuum degree≤- 0.090mpa
It is dry, obtain occrycetin fine grained salt finished product.
In the step (1), the 3kg zeolite powders after activation are added in the material being cooled to room temperature.
Wherein, the activation step of zeolite powder is：Zeolite powder, ethyl alcohol, acetone are uniformly mixed, are heated to 50 DEG C, is filtered, boiling
Mountain flour, ethyl alcohol, acetone proportioning be：1g:10ml:10ml.
In the step (2), compound resin is made of the raw material of following quality proportioning：X-5 macroporous absorbent resins 7
Part, 1 part of D3520 macroporous absorbent resins, 3 parts of DA-201 macroporous absorbent resins.
In the step (3), occrycetin wet product, acetone, ethyl alcohol, water, povidone k30, cation polypropylene
Amide, mannitol mass ratio be：10:1.05:2.45:1:1:0.7:0.55.
Embodiment 5
A kind of preparation method of occrycetin fine grained salt, includes the following steps：
(1) pre- water removal：100kg terramycin raw material and 350L ethyl alcohol are put into the first reaction kettle, heating distills out 2/3 body
Long-pending ethyl alcohol, is cooled to room temperature, then material in the first reaction kettle is centrifuged, and obtains the terramycin that water content is less than 0.1%
Wet product；
(2) at salt：15kg calcium chloride and 450L methanol are put into the second reaction kettle, it is molten that stirring and dissolving obtains calcium chloride methanol
Liquid, then step (1) obtained terramycin wet product is added into the second reaction kettle, stirring, 30 DEG C of low-grade fever are whole to terramycin wet product
After dissolving, adding 1kg compound resins, stirs, filtering obtains terramycin methanol solution, after terramycin methanol solution is cooled to room temperature,
30L hydrogen chloride methanol solutions are added, stirred crystallization is cooled to 5 DEG C, and filtering obtains occrycetin wet product and mother liquor, mother liquor is sent
Enter fluid reservoir；
(3) it bonds：By occrycetin wet product, acetone, ethyl alcohol, water, povidone k30, cationic polyacrylamide, sweet dew
Alcohol mixes according to the ratio, is uniformly mixed, is heated to 40 DEG C, obtains occrycetin powder；
(4) dry：The occrycetin powder that step (3) obtains is carried out under conditions of vacuum degree≤- 0.090mpa
It is dry, obtain occrycetin fine grained salt finished product.
In the step (1), the 2kg zeolite powders after activation are added in the material being cooled to room temperature.
Wherein, the activation step of zeolite powder is：Zeolite powder, ethyl alcohol, acetone are uniformly mixed, are heated to 50 DEG C, is filtered, boiling
Mountain flour, ethyl alcohol, acetone proportioning be：1g:15ml:10ml.
In the step (2), compound resin is made of the raw material of following quality proportioning：X-5 macroporous absorbent resins 8
Part, 3 parts of D3520 macroporous absorbent resins, 1 part of DA-201 macroporous absorbent resins.
In the step (3), occrycetin wet product, acetone, ethyl alcohol, water, povidone k30, cation polypropylene
Amide, mannitol mass ratio be：10:1.20:2.30:1:1:0.7:0.55.
Embodiment 6
A kind of preparation method of occrycetin fine grained salt, includes the following steps：
(1) pre- water removal：100kg terramycin raw material and 200L ethyl alcohol are put into the first reaction kettle, heating distills out 2/3 body
Long-pending ethyl alcohol, is cooled to room temperature, then material in the first reaction kettle is centrifuged, and obtains the terramycin that water content is less than 0.1%
Wet product；
(2) at salt：20kg calcium chloride and 350L methanol are put into the second reaction kettle, it is molten that stirring and dissolving obtains calcium chloride methanol
Liquid, then step (1) obtained terramycin wet product is added into the second reaction kettle, stirring, 35 DEG C of low-grade fever are whole to terramycin wet product
After dissolving, add 1.5kg compound resins, stir, filtering obtains terramycin methanol solution, waits for that terramycin methanol solution is cooled to room temperature
Afterwards, 35L hydrogen chloride methanol solutions are added, stirred crystallization is cooled to 5 DEG C, and filtering obtains occrycetin wet product and mother liquor, female
Liquid is sent into fluid reservoir；
(3) it bonds：By occrycetin wet product, acetone, ethyl alcohol, water, povidone k30, cationic polyacrylamide, sweet dew
Alcohol mixes according to the ratio, is uniformly mixed, is heated to 40 DEG C, obtains occrycetin powder；
(4) dry：The occrycetin powder that step (3) obtains is carried out under conditions of vacuum degree≤- 0.090mpa
It is dry, obtain occrycetin fine grained salt finished product.
In the step (1), the 1.5kg zeolite powders after activation are added in the material being cooled to room temperature.
Wherein, the activation step of zeolite powder is：Zeolite powder, ethyl alcohol, acetone are uniformly mixed, are heated to 50 DEG C, is filtered, boiling
Mountain flour, ethyl alcohol, acetone proportioning be：1g:15ml:10ml.
In the step (2), compound resin is made of the raw material of following quality proportioning：X-5 macroporous absorbent resins 6
Part, 2 parts of D3520 macroporous absorbent resins, 1 part of DA-201 macroporous absorbent resins.
In the step (3), occrycetin wet product, acetone, ethyl alcohol, water, povidone k30, cation polypropylene
Amide, mannitol mass ratio be：10:1.10:2.40:1:1:0.8:0.45.
Embodiment 7
A kind of preparation method of occrycetin fine grained salt, includes the following steps：
(1) pre- water removal：100kg terramycin raw material and 300L ethyl alcohol are put into the first reaction kettle, heating distills out 2/3 body
Long-pending ethyl alcohol, is cooled to room temperature, then material in the first reaction kettle is centrifuged, and obtains the terramycin that water content is less than 0.1%
Wet product；
(2) at salt：15kg calcium chloride and 400L methanol are put into the second reaction kettle, it is molten that stirring and dissolving obtains calcium chloride methanol
Liquid, then step (1) obtained terramycin wet product is added into the second reaction kettle, stirring, 35 DEG C of low-grade fever are whole to terramycin wet product
After dissolving, adding 1kg compound resins, stirs, filtering obtains terramycin methanol solution, after terramycin methanol solution is cooled to room temperature,
45L hydrogen chloride methanol solutions are added, stirred crystallization is cooled to 5 DEG C, and filtering obtains occrycetin wet product and mother liquor, mother liquor is sent
Enter fluid reservoir；
(3) it bonds：By occrycetin wet product, acetone, ethyl alcohol, water, povidone k30, cationic polyacrylamide, sweet dew
Alcohol mixes according to the ratio, is uniformly mixed, is heated to 35 DEG C, obtains occrycetin powder；
(4) dry：The occrycetin powder that step (3) obtains is carried out under conditions of vacuum degree≤- 0.090mpa
It is dry, obtain occrycetin fine grained salt finished product.
In the step (1), the 2.5kg zeolite powders after activation are added in the material being cooled to room temperature.
Wherein, the activation step of zeolite powder is：Zeolite powder, ethyl alcohol, acetone are uniformly mixed, are heated to 50 DEG C, is filtered, boiling
Mountain flour, ethyl alcohol, acetone proportioning be：1g:20ml:10ml.
In the step (2), compound resin is made of the raw material of following quality proportioning：X-5 macroporous absorbent resins 9
Part, 1 part of D3520 macroporous absorbent resins, 2 parts of DA-201 macroporous absorbent resins.
In the step (3), occrycetin wet product, acetone, ethyl alcohol, water, povidone k30, cation polypropylene
Amide, mannitol mass ratio be：10:1.25:2.45:1:1:0.8:0.50.
Comparative example 1 (technological parameter not within the scope of the present invention)
A kind of preparation method of occrycetin fine grained salt, includes the following steps：
(1) pre- water removal：100kg terramycin raw material and 450L ethyl alcohol are put into the first reaction kettle, heating distills out 1/3 body
Long-pending ethyl alcohol, is cooled to room temperature, then material in the first reaction kettle is centrifuged, and obtains the terramycin that water content is less than 0.1%
Wet product；
(2) at salt：25kg calcium chloride and 300L methanol are put into the second reaction kettle, it is molten that stirring and dissolving obtains calcium chloride methanol
Liquid, then step (1) obtained terramycin wet product is added into the second reaction kettle, stirring, 30 DEG C of low-grade fever are whole to terramycin wet product
After dissolving, add 2.0kg compound resins, stir, filtering obtains terramycin methanol solution, waits for that terramycin methanol solution is cooled to room temperature
Afterwards, 25L hydrogen chloride methanol solutions are added, stirred crystallization is cooled to 5 DEG C, and filtering obtains occrycetin wet product and mother liquor, female
Liquid is sent into fluid reservoir；
(3) it bonds：By occrycetin wet product, acetone, ethyl alcohol, water, povidone k30, cationic polyacrylamide, sweet dew
Alcohol mixes according to the ratio, is uniformly mixed, is heated to 40 DEG C, obtains occrycetin powder；
(4) dry：The occrycetin powder that step (3) obtains is carried out under conditions of vacuum degree≤- 0.090mpa
It is dry, obtain occrycetin fine grained salt finished product.
In the step (1), 4kg zeolite powders after activation are added in the material being cooled to room temperature.
Wherein, the activation step of zeolite powder is：Zeolite powder, ethyl alcohol, acetone are uniformly mixed, are heated to 50 DEG C, is filtered, boiling
Mountain flour, ethyl alcohol, acetone proportioning be：1g:5ml:10ml.
In the step (2), compound resin is made of the raw material of following quality proportioning：X-5 macroporous absorbent resins 3
Part, 5 parts of D3520 macroporous absorbent resins, 5 parts of DA-201 macroporous absorbent resins.
In the step (3), occrycetin wet product, acetone, ethyl alcohol, water, povidone k30, cation polypropylene
Amide, mannitol mass ratio be：10:1.3:2.0:1:1:0.6:0.6.
Comparative example 2 (is not added with zeolite powder)
A kind of preparation method of occrycetin fine grained salt, includes the following steps：
(1) pre- water removal：100kg terramycin raw material and ethyl alcohol are put into the first reaction kettle, heating distills out 1/2 volume
Ethyl alcohol is cooled to room temperature, then material in the first reaction kettle is centrifuged, and obtains the terramycin wet product that water content is less than 0.1%；
In the step (1), zeolite powder is added without in the material being cooled to room temperature.
Remaining is the same as embodiment 1.
Comparative example 3 (zeolite powder is unactivated)
A kind of preparation method of occrycetin fine grained salt, includes the following steps：
(1) pre- water removal：100kg terramycin raw material and ethyl alcohol are put into the first reaction kettle, heating distills out 2/3 volume
Ethyl alcohol is cooled to room temperature, then material in the first reaction kettle is centrifuged, and obtains the terramycin wet product that water content is less than 0.1%；
In the step (1), zeolite powder is directly added into the material being cooled to room temperature.
Remaining is the same as embodiment 2.
Comparative example 4 (activated carbon decolourizes)
A kind of preparation method of occrycetin fine grained salt, includes the following steps：
It is same as Example 3, in addition to following steps：
(2) at salt：Calcium chloride and methanol are put into the second reaction kettle, stirring and dissolving obtains calcium chloride methanol solution, then to
The terramycin wet product that step (1) obtains is added in second reaction kettle, stirs, after 40 DEG C of low-grade fever is all dissolved to terramycin wet product,
Add activated carbon, heat and stir, filters, obtain terramycin methanol solution, after terramycin methanol solution is cooled to room temperature, add
Hydrogen chloride methanol solution, stirred crystallization are cooled to 5 DEG C, and filtering obtains occrycetin wet product and mother liquor, and mother liquor is sent into fluid reservoir.
Comparative example 5 (not plus D3520 macroporous absorbent resins)
A kind of preparation method of occrycetin fine grained salt, includes the following steps：
It is same as Example 4, in addition to following steps：
Compound resin is made of the raw material of following quality proportioning：7 parts of X-5 macroporous absorbent resins, DA-201 macroporous absorption trees
3 parts of fat.
Comparative example 6 (not plus cationic polyacrylamide and mannitol)
A kind of preparation method of occrycetin fine grained salt, includes the following steps：
It is same as Example 5, in addition to following steps：
(3) it bonds：Occrycetin wet product, acetone, ethyl alcohol, water, povidone k30 are mixed according to the ratio, is uniformly mixed, adds
Heat obtains occrycetin powder to 40 DEG C；
Occrycetin wet product, acetone, ethyl alcohol, water, povidone k30 mass ratio be：10:1.20:2.30:1:1.
The invention is not limited in above-mentioned specific implementation mode, those skilled in the art can also make a variety of variations accordingly,
But it is any all to cover within the scope of the claims with equivalent or similar variation of the invention.
The occrycetin particulate product salt effect that each embodiment and comparative example obtain is as shown in the table：
Absorbance × 100% before percent of decolourization=(absorbance after absorbance-decoloration before decoloration)/decolorization process.
Occrycetin particulate product salt effect made from each embodiment of 1 present invention of table and comparative example
| Group | Mass yield (%) | Percent of decolourization (%) | Granularity (μm) | Bulk density (g/ml) |
| Embodiment 1 | 98.81 | 90.8 | 153 | 0.45 |
| Embodiment 2 | 99.36 | 93.6 | 186 | 0.58 |
| Embodiment 3 | 99.05 | 93.0 | 179 | 0.53 |
| Embodiment 4 | 98.92 | 92.2 | 158 | 0.49 |
| Embodiment 5 | 99.19 | 91.5 | 161 | 0.55 |
| Embodiment 6 | 99.23 | 92.9 | 175 | 0.52 |
| Embodiment 7 | 98.98 | 92.1 | 184 | 0.48 |
| Comparative example 1 | 93.46 | 86.7 | 102 | 0.37 |
| Comparative example 2 | 87.50 | 83.8 | 110 | 0.32 |
| Comparative example 3 | 91.37 | 85.3 | 109 | 0.38 |
| Comparative example 4 | 92.74 | 82.7 | 114 | 0.35 |
| Comparative example 5 | 93.96 | 86.0 | 117 | 0.34 |
| Comparative example 6 | 94.23 | 90.5 | 51 | 0.30 |
Occrycetin particulate product salt effect made from the embodiment of the present invention 1-6 is can be seen that from upper table data all
Better than comparative example 1 (technological parameter not within the scope of the present invention), comparative example 2 (being not added with zeolite powder), comparative example 3, (zeolite powder is lived
Change), comparative example 4 (activated carbon decolourizes), comparative example 5 (not plus D3520 macroporous absorbent resins), comparative example 6 (not plus cation
Polyacrylamide and mannitol), it is especially optimal with the effect of embodiment 2.It can be seen that the present invention is preparing occrycetin fine grained salt
During, it is cleaned in advance using the zeolite powder after activation in pre- the step of removing water first, then using multiple before at salt
Resin is decolourized and is cleaned, finally select povidone k30 and cationic polyacrylamide, mannitol etc. as adhesive and
Adhesion promoter has an impact the effect of occrycetin fine grained salt obtained, therefore the above each technical characteristic of the present invention,
Synergistic effect, occrycetin fine grained salt obtained not only high income, but also improve percent of decolourization, while increasing granularity and pine is close
Degree, can meet the needs of subsequent production.
Claims (10)
1. a kind of preparation method of occrycetin fine grained salt, it is characterized in that：Include the following steps：
(1) pre- water removal：Terramycin raw material and ethyl alcohol are put into the first reaction kettle, heating distills out the ethyl alcohol of 1/2-2/3 volumes,
It is cooled to room temperature, then material in the first reaction kettle is centrifuged, obtain the terramycin wet product that water content is less than 0.1%；
(2) at salt：Calcium chloride and methanol are put into the second reaction kettle, stirring and dissolving obtains calcium chloride methanol solution, then to second
The terramycin wet product that step (1) obtains is added in reaction kettle, stirring adds after 30-40 DEG C of low-grade fever is all dissolved to terramycin wet product
Compound resin stirs, and filtering obtains terramycin methanol solution, after terramycin methanol solution is cooled to room temperature, adds hydrogen chloride
Methanol solution, stirred crystallization are cooled to 5 DEG C, and filtering obtains occrycetin wet product and mother liquor, and mother liquor is sent into fluid reservoir；
(3) it bonds：Occrycetin wet product, acetone, ethyl alcohol, water, povidone k30, cationic polyacrylamide, mannitol are pressed
Proportioning mixing, is uniformly mixed, is heated to 35-40 DEG C, obtains occrycetin powder；
(4) dry：The occrycetin powder that step (3) obtains is dried under conditions of vacuum degree≤- 0.090mpa,
Obtain occrycetin fine grained salt finished product.
2. a kind of preparation method of occrycetin fine grained salt as described in claim 1, it is characterized in that：In the step
(1) in, the solid-liquid ratio of terramycin raw material and ethyl alcohol is：1kg:2-4L.
3. a kind of preparation method of occrycetin fine grained salt as described in claim 1, it is characterized in that：In the step
(1) in, the zeolite powder after activation is added in the material being cooled to room temperature, the addition of zeolite powder is terramycin material quality
1-3%.
4. a kind of preparation method of occrycetin fine grained salt as claimed in claim 3, it is characterized in that：Wherein, zeolite powder
Activation step is：Zeolite powder, ethyl alcohol, acetone are uniformly mixed, are heated to 50 DEG C, filtering, zeolite powder, ethyl alcohol, acetone proportioning
For：1g:10-20ml:10ml.
5. a kind of preparation method of occrycetin fine grained salt as described in claim 1, it is characterized in that：In the step
(2) in, the solid-liquid ratio of terramycin raw material and methanol is：1kg:3.5-4.5L.
6. a kind of preparation method of occrycetin fine grained salt as described in claim 1, it is characterized in that：In the step
(2) in, the mass ratio of terramycin raw material and calcium chloride is：1:0.1-0.2.
7. a kind of preparation method of occrycetin fine grained salt as described in claim 1, it is characterized in that：In the step
(2) in, the dosage of compound resin is the 0.5-1.5% of terramycin material quality.
8. a kind of preparation method of occrycetin fine grained salt as claimed in claim 8, it is characterized in that：Wherein, compound resin
It is made of the raw material of following quality proportioning：5-10 parts of X-5 macroporous absorbent resins, 1-3 parts of D3520 macroporous absorbent resins, DA-201
1-3 parts of macroporous absorbent resin.
9. a kind of preparation method of occrycetin fine grained salt as described in claim 1, it is characterized in that：In the step
(2) in, the solid-liquid ratio of terramycin raw material and hydrogen chloride methanol solution is：1kg:0.3-0.5L.
10. a kind of preparation method of occrycetin fine grained salt as described in claim 1, it is characterized in that：In the step
(3) in, occrycetin wet product, acetone, ethyl alcohol, water, povidone k30, cationic polyacrylamide, mannitol mass ratio
For：10:1.05-1.25:2.25-2.45:1:1:0.7-0.9:0.45-0.55.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201810526138.3A CN108586277B (en) | 2018-05-29 | 2018-05-29 | Preparation method of oxytetracycline hydrochloride fine particle salt |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201810526138.3A CN108586277B (en) | 2018-05-29 | 2018-05-29 | Preparation method of oxytetracycline hydrochloride fine particle salt |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN108586277A true CN108586277A (en) | 2018-09-28 |
| CN108586277B CN108586277B (en) | 2020-12-04 |
Family
ID=63629378
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201810526138.3A Active CN108586277B (en) | 2018-05-29 | 2018-05-29 | Preparation method of oxytetracycline hydrochloride fine particle salt |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN108586277B (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN115124439A (en) * | 2022-08-13 | 2022-09-30 | 安徽一灵药业有限公司 | Synthesis process of oxytetracycline hydrochloride |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1090268A (en) * | 1993-11-12 | 1994-08-03 | 清华大学 | Production of oxytetracycline hydrochloride |
| 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
- 2018-05-29 CN CN201810526138.3A patent/CN108586277B/en active Active
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1090268A (en) * | 1993-11-12 | 1994-08-03 | 清华大学 | Production of oxytetracycline hydrochloride |
| 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 (1)
| Title |
|---|
| 王立志等: "土霉素盐酸盐在不同溶剂中溶解度的测定与关联", 《北京工商大学学报(自然科学版)》 * |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN115124439A (en) * | 2022-08-13 | 2022-09-30 | 安徽一灵药业有限公司 | Synthesis process of oxytetracycline hydrochloride |
Also Published As
| Publication number | Publication date |
|---|---|
| CN108586277B (en) | 2020-12-04 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN112409132B (en) | Method for separating inositol and by-products | |
| CN102659818B (en) | Hydrochloric acid cefotiam crystalline compound, preparation method thereof and medicine combination containing compound | |
| CN112299954A (en) | Process for preparing inositol and by-products | |
| CN108484607A (en) | Novel preparation method of tofacitinib citrate | |
| CN108586277A (en) | A kind of preparation method of occrycetin fine grained salt | |
| CN113004320A (en) | Method for reducing consumption of desorbent in production of inositol | |
| CN107011205A (en) | A kind of method for producing large-grain occrycetin | |
| CN109096129B (en) | Preparation method of L-carnitine tartrate | |
| CN103059028A (en) | Preparation method of tebipenem pivoxil | |
| JP5132225B2 (en) | Amorphous spherical aluminum silicate, method for producing the same, and preparation using the aluminum silicate. | |
| CN107814802A (en) | A kind of new method for preparing citric acid tropsch imatinib medicinal crystal-form | |
| CN106496295A (en) | The preparation method of Suo Feibuwei crystal formations 6 | |
| EP4424660A1 (en) | Preparation system and method for xylitol crystal | |
| CN103167872A (en) | Process for the production of l-carnitine tartrate | |
| CN106674321A (en) | Preparation method of sofosbuvir crystal form 6 | |
| CN114288259B (en) | Quick-release preparation of vitamin B2 and preparation method thereof | |
| CN110559265A (en) | preparation method of acetyl L-carnitine arginine dihydrochloride moisture-proof particles | |
| CN102241599B (en) | Method for preparing glycine | |
| CN115260210A (en) | Cepharanthine crystal form and preparation method thereof | |
| CN101612551B (en) | Preparation of medical sodium benzoate | |
| CN110922301B (en) | Method for extracting sugar alcohol from chewing gum waste | |
| CN103554136A (en) | Preparation method of cefmenoxine hydrochloride dry powder | |
| CN104555963A (en) | Method for recycling waste phosphoric acid during production of butachlor | |
| CN103818911A (en) | Preparation method of high-adsorption-value and adjustable pore volume micropowder silica gel | |
| CN103172532A (en) | Preparation method of ethylenediaminetetraacetic acid calcium disodium salt |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant |