CN109394707A - A kind of manufacturing method of injection caspofungin acetate - Google Patents
A kind of manufacturing method of injection caspofungin acetate Download PDFInfo
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- CN109394707A CN109394707A CN201811598506.1A CN201811598506A CN109394707A CN 109394707 A CN109394707 A CN 109394707A CN 201811598506 A CN201811598506 A CN 201811598506A CN 109394707 A CN109394707 A CN 109394707A
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- caspofungin acetate
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- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/19—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles lyophilised, i.e. freeze-dried, solutions or dispersions
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- A61K38/12—Cyclic peptides, e.g. bacitracins; Polymyxins; Gramicidins S, C; Tyrocidins A, B or C
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Abstract
The invention discloses a kind of manufacturing methods of injection caspofungin acetate, comprising the following steps: 1) prepares Caspofungin solution by initial feed of Pneumocandin B0, acetic acid is added and obtains caspofungin acetate solution；2) caspofungin acetate solution is passed through drying tower to be dried in vacuo, removes the organic solvent in caspofungin acetate；3) the resulting caspofungin acetate of step 2) is obtained into injection caspofungin acetate through dissolution, ultrafiltration, freeze-drying.Using the purity is high of the injection caspofungin acetate of this method preparation, product stability is good.
Description
Technical field
The present invention relates to drug manufacturing fields, and in particular to a kind of manufacturing method of injection caspofungin acetate.
Background technique
Injection caspofungin acetate needle can be used for empirical treatment Neutrophilic granulocytopenia, with the suspicious true of fever patient
Bacterium infects and treats invalid to other treatments or intolerable invasive aspergillosis.Caspofungin is to Eurotium (packet
Include aspergillus fumigatus, Aspergillus flavus, black-koji mould, aspergillus nidulans, aspergillus terreus and aspergillus candidus) and Mycotoruloides (including it is white
Color candida albicans, Candida dubliniensis, Candida glabrata, candida guilliermondi, Candida kefyr, candida krusei, fat melting are read
Pearl bacterium, Candida lusitaniae, Candida parapsilosis, candida rugosa and Candida tropicalis) there is external activity, acetic acid card pool is fragrant
Net energy inhibits the synthesis of many filamentous fungis and yeast cell wall β (1,3)-D- glucan, thus inhibit the breeding of pathogen,
P (1,3)-D- glucan is not present in the cell of mammal, thus for the Small side effects of human body.
Currently, methanol, ethyl alcohol, ethyl acetate, tetrahydro furan would generally be used in the preparation process of existing caspofungin acetate
It mutters, isopropanol, acetonitrile equal solvent, purification difficult, solvent content is generally difficult to reach in the caspofungin acetate finished product because prepared by
To the relevant regulations of dissolvent residual, while resulting product stability is poor, needs cryo-conservation, improve caspofungin acetate at
The cost they product transport and saved.
Summary of the invention
In order to solve the above-mentioned technical problem, the present invention discloses a kind of manufacturing method of injection caspofungin acetate, utilizes
The purity is high of the injection caspofungin acetate of this method preparation, product stability are good.
The present invention is achieved through the following technical solutions:
A kind of manufacturing method of injection caspofungin acetate, comprising the following steps:
1) Caspofungin solution is prepared by initial feed of Pneumocandin B0, it is molten that addition acetic acid obtains caspofungin acetate
Liquid；
2) caspofungin acetate solution is passed through drying tower to be dried in vacuo, is removed organic molten in caspofungin acetate
Agent；
3) the resulting caspofungin acetate of step 2) is obtained into injection caspofungin acetate through dissolution, ultrafiltration, freeze-drying.
Wherein, in the step 2), vacuum drying process includes the following steps；
21) caspofungin acetate solution is sprayed into drying tower through atomizer, forms caspofungin acetate droplet, simultaneously
It is passed through high temperature helium into drying tower and carries out heat exchange；
22) stop being passed through caspofungin acetate solution and high temperature helium, then using in the first vacuum pump extraction drying tower
The organic solvent of helium and vaporization in chamber；
23) the first vacuum pump is closed, continues to be filled with high temperature helium into drying tower, while being filled with vapor, in drying tower
After air pressure and the external world are consistent, stopping is filled with high temperature helium and vapor, is then turned in the first vacuum pump extraction drying tower inner cavity
Helium and vaporization organic solvent；
24) caspofungin acetate particle is obtained after repeating step 23) 1-4 times, caspofungin acetate particle is concentrated on one
In a Material collecting box for harvesting, pure water is added and is configured to caspofungin acetate concentrated solution；
25) Material collecting box for harvesting is vacuumized using the second vacuum pump, dry caspofungin acetate concentrated solution, the vinegar after being purified
Sour Caspofungin.
In the present invention, the existing conventional technique that Caspofungin solution is prepared using Pneumocandin B0 is can be used in step 1),
Caspofungin acetate solution obtained contains a large amount of organic solvents, as methanol, ethyl alcohol, ethyl acetate, tetrahydrofuran, isopropanol,
Acetonitrile, caspofungin acetate solution spray into drying tower inner cavity after being atomized, and form caspofungin acetate droplet in drying tower inner cavity,
The high temperature helium being passed through can be moved up to be contacted with caspofungin acetate droplet, the solvent heat absorption in caspofungin acetate droplet
After be volatilized into steam, achieve the effect that remove caspofungin acetate droplet in solvent, improve the purity of caspofungin acetate, keep away
Exempt from caspofungin acetate degradation, improves the stability of product.
In the present invention, the first vacuum pump extracts the helium in drying tower inner cavity and the organic solvent of vaporization out, and then makes drying
Caspofungin acetate droplet in tower is in subnormal ambient, promotes the continued vaporization of solvent to volatilize, when caspofungin acetate droplet
When being dried to the caspofungin acetate particle with certain moisture content, the vapor that is passed through and it is dried to a degree of acetic acid card
Residual organic solvent in the fragrant net particle of pool combines, and organic solvent is dried in vacuo to removing together under the effect of high temperature helium,
It can be largely avoided that in conjunction with vapor with the nitrogen oxygen atom of water vapour formation hydrogen bond since caspofungin acetate itself contains
The crystal structure of the caspofungin acetate particle of sample is closed, and then holds remaining organic solvent in caspofungin acetate particle
It is continuous to be removed with the vacuum drying of vapor knot merga pass, significantly reduce the residual of organic solvent in the caspofungin acetate particle of preparation
Allowance.
After step 23) 1-4 times, the organic solvent content in caspofungin acetate particle is substantially reduced, caspofungin acetate
Particle enters eventually into Material collecting box for harvesting after collecting, after adding pure water to be configured to concentrated solution, under the action of the second vacuum pump further
Dry caspofungin acetate particle, removes residual solvent, keeps the removal of residual organic solvent more thorough, and it is fragrant to improve acetic acid card pool
Net purity.
Further, in the step 3), caspofungin acetate dissolution, ultrafiltration, freeze-drying specifically comprises the processes of:
31) excipient and PH regulator are added in a reaction kettle, are then added water for injection, it, will after stirring and dissolving
Reaction kettle, stirring and dissolving is added in caspofungin acetate obtained；
32) mixture solution obtained by step 31) is subjected to ultrafiltration after reaction kettle taking-up under low temperature, hyperbaric environment, then
By product bottling, freeze-drying.
In the step 22), after stopping is passed through caspofungin acetate solution and high temperature helium, need to caspofungin acetate
After droplet and high temperature helium heat exchange reaction continue 1-3min, recycle helium in the first vacuum pump extraction drying tower inner cavity with
The organic solvent of vaporization.Organic solvent and high temperature helium in caspofungin acetate droplet is set to carry out sufficient heat exchange, in turn
So that organic solvent is vaporized volatilization as far as possible, is detached from caspofungin acetate droplet.
In the step 23), after stopping is filled with high temperature helium and vapor, need to steam to caspofungin acetate particle and water
After gas, high temperature helium react lasting 2-4min, the helium being then turned in the first vacuum pump extraction drying tower inner cavity has with what is vaporized
Solvent.It combines vapor sufficiently sufficiently with caspofungin acetate particle, and improves molecular motion with high temperature helium heat exchange
Active degree promotes remaining organic solvent in caspofungin acetate particle to continue to vaporize and then extract drying out under negative pressure of vacuum
Tower inner cavity further increases the purity of caspofungin acetate.
In the step 22), pipeline one is entered by the organic solvent of helium and vaporization that the first vacuum pump is extracted out, through pipeline
It is entered in a gas-liquid separation device after the condensing unit cooling of one outer wall, organic solvent pre-cooling liquefaction, helium enters one
In the pipeline two being connected with gas-liquid separation device, pipeline two connects a helium storage box, the storage injection of helium storage box use
The helium of drying tower inner cavity.The recycling of helium is realized, operating cost is reduced.
In the step 23), vapor pass through a heating water tanks pure water after obtain, the condensing unit using pure water as
Coolant liquid is entered in water tank after coolant liquid heat exchange by pipeline three, water tank by the pipeline five with valve with gather materials
Case is connected.
In the present invention, the condensed water of condensing unit enters heating evaporation in water tank by pipeline three, realizes the weight of water
It is multiple to utilize, simultaneously because the condensate temperature after heat exchange is higher than light water, is heated after entering water tank, water tank can be reduced and added
The heating time of thermal element and energy consumption can connect energy conservation, reduce the manufacturing cost of caspofungin acetate.
In the step 22), the organic solvent using helium and vaporization in the first vacuum pump extraction drying tower inner cavity is logical
It crosses the exhaust tube connecting with drying tower top plate to realize, filter device, filter device is equipped between exhaust tube and drying tower inner cavity
It is interior to be equipped with microfiltration membranes and/or ultrafiltration membrane.
Microfiltration membranes and ultrafiltration membrane can effectively avoid caspofungin acetate particle from entering exhaust tube, avoid acetic acid card
The fragrant net waste of pool.
Compared with prior art, the present invention having the following advantages and benefits:
1, a kind of manufacturing method of injection caspofungin acetate of the present invention, caspofungin acetate solution spray into after being atomized
Drying tower inner cavity forms caspofungin acetate droplet in drying tower inner cavity, and the high temperature helium being passed through can move up and acetic acid
Caspofungin droplet contacts, and is volatilized into steam after the solvent heat absorption in caspofungin acetate droplet, reaches and removes acetic acid card pool sweet smell
The effect of solvent in net droplet, improves the purity of caspofungin acetate, caspofungin acetate is avoided to degrade, improve the steady of product
It is qualitative；
2, a kind of manufacturing method of injection caspofungin acetate of the present invention, the first vacuum pump are extracted out in drying tower inner cavity
The organic solvent of helium and vaporization, and then the caspofungin acetate droplet in drying tower is made to be in subnormal ambient, promote solvent
Continued vaporization volatilization, when caspofungin acetate droplet is dried to the caspofungin acetate particle with certain moisture content, is passed through
Vapor in conjunction with the residual organic solvent being dried in a degree of caspofungin acetate particle, and high temperature helium make
With lower organic solvent is dried in vacuo to removing together, largely can form hydrogen with water vapour since caspofungin acetate itself contains
The nitrogen oxygen atom of key, is avoided that the crystal structure closure of the caspofungin acetate particle of sample in conjunction with vapor, and then makes vinegar
Remaining organic solvent continues in sour Caspofungin particle and the vacuum drying of vapor knot merga pass removes, and significantly reduces preparation
Caspofungin acetate particle in organic solvent residual quantity.
Detailed description of the invention
Attached drawing described herein is used to provide to further understand the embodiment of the present invention, constitutes one of the application
Point, do not constitute the restriction to the embodiment of the present invention.In the accompanying drawings:
Fig. 1 is drying tower structural schematic diagram of the present invention；
Fig. 2 is drying tower filter device cross-sectional view of the present invention.
Label and corresponding parts title in attached drawing:
1- drying tower, 11- bottom plate, 12- side plate, 13- top plate, 14- partition, 15- guide shell, 16- discharge nozzle, 2- atomization spray
Mouth, 21- conduit, 22- liquid reserve tank, 23- booster pump, 3- air nozzle, 31- gas-guide tube, 32- helium storage box, 33- air pump, 34- helium
Air purifying apparatus, 4- exhaust tube, the first vacuum pump of 41-, 42- pipeline one, 43- gas-liquid separation device, 44- pipeline two, 45- waste liquid
Recyclable device, 5- condensing unit, 51- pipeline three, 6- water tank, 61- exhaust pipe, 62- pipeline five, 7- Material collecting box for harvesting, 71- pipeline four,
The second vacuum pump of 72-, 73- drainage conduit, 8- gas gathering mask, 81- filter device, 82- mounting plate, 83- microfiltration membranes, 84- ultrafiltration membrane, 9-
Reaction kettle, 91- excipient feed pipe, 92-PH regulator feed pipe, 10-PLC controller.
Specific embodiment
To make the objectives, technical solutions, and advantages of the present invention clearer, below with reference to embodiment and attached drawing, to this
Invention is described in further detail, and exemplary embodiment of the invention and its explanation for explaining only the invention, are not made
For limitation of the invention.
Embodiment 1
As shown in Figure 1, a kind of manufacturing method of injection caspofungin acetate of the present invention, comprising the following steps:
1) Caspofungin solution is prepared by initial feed of Pneumocandin B0, it is molten that addition acetic acid obtains caspofungin acetate
Liquid；
2) caspofungin acetate solution is passed through drying tower 1 to be dried in vacuo, is removed organic in caspofungin acetate
Solvent；
3) the resulting caspofungin acetate of step 2) is obtained into injection caspofungin acetate through dissolution, ultrafiltration, freeze-drying.
Wherein, in the step 2), vacuum drying process includes the following steps；
21) caspofungin acetate solution is sprayed into drying tower 1 through atomizer, forms caspofungin acetate droplet, together
When be passed through into drying tower 1 high temperature helium carry out heat exchange；
22) stop being passed through caspofungin acetate solution and high temperature helium, then extract drying tower 1 out using the first vacuum pump 41
The organic solvent of helium and vaporization in inner cavity；
23) the first vacuum pump 41 is closed, continues to be filled with high temperature helium into drying tower 1, while being filled with vapor, drying tower
After air pressure and the external world are consistent in 1, stopping is filled with high temperature helium and vapor, is then turned on the first vacuum pump 41 extraction drying tower 1
The organic solvent of helium and vaporization in inner cavity；
24) caspofungin acetate particle is obtained after repeating step 23) 1-4 times, caspofungin acetate particle is concentrated on one
In a Material collecting box for harvesting 7, pure water is added and is configured to caspofungin acetate concentrated solution；
25) Material collecting box for harvesting 7 is vacuumized using the second vacuum pump 72, dry caspofungin acetate concentrated solution, after obtaining purification
Caspofungin acetate.
Further, in the step 3), caspofungin acetate dissolution, ultrafiltration, freeze-drying specifically comprises the processes of:
31) excipient and PH regulator are added in a reaction kettle 9, are then added water for injection, it, will after stirring and dissolving
Reaction kettle 9, stirring and dissolving is added in caspofungin acetate obtained；
32) mixture solution obtained by step 31) is subjected to ultrafiltration after the taking-up of reaction kettle 9 under low temperature, hyperbaric environment, then
By product bottling, freeze-drying.
In the step 22), after stopping is passed through caspofungin acetate solution and high temperature helium, need to caspofungin acetate
After droplet and high temperature helium heat exchange reaction continue 1-3min, the helium in the first vacuum pump 41 extraction 1 inner cavity of drying tower is recycled
The organic solvent of gas and vaporization.
In the step 23), after stopping is filled with high temperature helium and vapor, need to steam to caspofungin acetate particle and water
The helium being then turned in the first vacuum pump 41 extraction 1 inner cavity of drying tower after gas, high temperature helium react lasting 2-4min and vaporization
Organic solvent.
Embodiment 2
As shown in Figure 1, 2, a kind of manufacturing method of injection caspofungin acetate of the present invention, comprising the following steps:
1) Caspofungin solution is prepared by initial feed of Pneumocandin B0, it is molten that addition acetic acid obtains caspofungin acetate
Liquid；
2) caspofungin acetate solution is passed through drying tower 1 to be dried in vacuo, is removed organic in caspofungin acetate
Solvent；
3) the resulting caspofungin acetate of step 2) is obtained into injection caspofungin acetate through dissolution, ultrafiltration, freeze-drying.
Wherein, in the step 2), vacuum drying process includes the following steps；
21) caspofungin acetate solution is sprayed into drying tower 1 through atomizer, forms caspofungin acetate droplet, together
When be passed through into drying tower 1 high temperature helium carry out heat exchange；
22) stop being passed through caspofungin acetate solution and high temperature helium, then extract drying tower 1 out using the first vacuum pump 41
The organic solvent of helium and vaporization in inner cavity；
23) the first vacuum pump 41 is closed, continues to be filled with high temperature helium into drying tower 1, while being filled with vapor, drying tower
After air pressure and the external world are consistent in 1, stopping is filled with high temperature helium and vapor, is then turned on the first vacuum pump 41 extraction drying tower 1
The organic solvent of helium and vaporization in inner cavity；
24) caspofungin acetate particle is obtained after repeating step 23) 1-4 times, caspofungin acetate particle is concentrated on one
In a Material collecting box for harvesting 7, pure water is added and is configured to caspofungin acetate concentrated solution；
25) Material collecting box for harvesting 7 is vacuumized using the second vacuum pump 72, dry caspofungin acetate concentrated solution, after obtaining purification
Caspofungin acetate.
Further, in the step 3), caspofungin acetate dissolution, ultrafiltration, freeze-drying specifically comprises the processes of:
31) excipient and PH regulator are added in a reaction kettle 9, are then added water for injection, it, will after stirring and dissolving
Reaction kettle 9, stirring and dissolving is added in caspofungin acetate obtained；
32) mixture solution obtained by step 31) is subjected to ultrafiltration after the taking-up of reaction kettle 9 under low temperature, hyperbaric environment, then
By product bottling, freeze-drying.
In the step 22), after stopping is passed through caspofungin acetate solution and high temperature helium, need to caspofungin acetate
After droplet and high temperature helium heat exchange reaction continue 1-3min, the helium in the first vacuum pump 41 extraction 1 inner cavity of drying tower is recycled
The organic solvent of gas and vaporization.
In the step 23), after stopping is filled with high temperature helium and vapor, need to steam to caspofungin acetate particle and water
The helium being then turned in the first vacuum pump 41 extraction 1 inner cavity of drying tower after gas, high temperature helium react lasting 2-4min and vaporization
Organic solvent.
In the step 22), pipeline 1 is entered by the organic solvent of the first helium extracted out of vacuum pump 41 and vaporization, is passed through
The condensing unit 5 of one 42 outer wall of pipeline enters in a gas-liquid separation device 43 after cooling down, organic solvent pre-cooling liquefaction, helium
Into in a pipeline being connected with gas-liquid separation device 43 2 44, pipeline 2 44 connects a helium storage box 32, and helium is deposited
The helium of 32 use of storage tank storage injection, 1 inner cavity of drying tower.
In the step 23), vapor obtains after heating pure water by a water tank 6, and the condensing unit 5 is made with pure water
For coolant liquid, entered in water tank 6 after coolant liquid heat exchange by pipeline 3 51, water tank 6 passes through the pipeline five with valve
62 are connected with Material collecting box for harvesting 7.
In the step 22), the organic solvent of helium and vaporization in the first vacuum pump 41 extraction 1 inner cavity of drying tower is utilized
It is realized by an exhaust tube 4 being connect with 1 top plate 13 of drying tower, filter device is equipped between 1 inner cavity of exhaust tube 4 and drying tower
81, filter device 81 is interior to be equipped with microfiltration membranes 83 and/or ultrafiltration membrane 84.
Drying tower structure used in the present embodiment is as follows:
Drying tower 1 includes bottom plate 11, side plate 12 and top plate 13, and top plate 13 is equipped with several atomizers 2, and atomizer 2 is worn
Top plate 13 is crossed towards bottom plate 11, connects one for storage of acetic acid Caspofungin solution by conduit 21 at the top of atomizer 2
Liquid reserve tank 22,1 side plate 12 of drying tower are equipped with an air nozzle 3, and air nozzle 3 is stored by gas-guide tube 31 and a helium
Case 32 connects.
1 top plate 13 of drying tower is equipped with an exhaust tube 4, and exhaust tube 4 is connected with the first vacuum pump 41, the first vacuum
It pumps 41 other ends and one gas-liquid separation device 43 is connected by pipeline 1, the exhaust end of gas-liquid separation device 43 passes through pipeline two
44 are connected with helium storage box 32, and drain side is connected with a waste liquid recovery apparatus 45.
The pipeline 1 is equipped with a condensing unit 5, and condensing unit 5 is equipped with water inlet end and water outlet, and water outlet is logical
Piping 3 51 is connected with a water tank 6, and heating element is equipped in water tank 6, is equipped with exhaust pipe 61, exhaust pipe 61 at the top of water tank 6
It is connected to 1 inner cavity of drying tower, is additionally provided with non-return valve at the top of exhaust pipe 61.
1 inner cavity of drying tower is equipped with partition 14, and a guide shell 15 is equipped with above partition 14, and guide shell 15 is in back taper
Shape, 15 top surface of guide shell are fixedly linked with 1 side plate 12 of drying tower, and bottom surface is connected with a discharge nozzle 16 with valve, discharge nozzle
16 bottoms pass through partition 14, and a Material collecting box for harvesting 7,7 top of Material collecting box for harvesting and discharge nozzle are equipped in the drying tower 1 of 14 lower section of partition
16 connections, 7 side wall of Material collecting box for harvesting are connected with pipeline 4 71, and pipeline 4 71 is connected with the second vacuum pump 72.
1 top plate of drying tower, 13 center is equipped with the gas gathering mask 8 of a taper, 8 bottom edge of gas gathering mask and 13 phase of top plate
Connection, 8 top of gas gathering mask are connected with exhaust tube 4, and filter device 81 is equipped between 4 inner cavity of exhaust tube and 1 inner cavity of drying tower.
The water tank 6 is arranged in the cavity between partition 14 and guide shell 15, and guide shell 15, water are passed through at the top of exhaust pipe 61
6 bottom of case is equipped with the pipeline 5 62 of provided with electromagnetic valve, and pipeline 5 62 passes through partition 14 and connect with Material collecting box for harvesting 7.
7 bottom of Material collecting box for harvesting is equipped with the drainage conduit 73 with valve, and drainage conduit 73 passes through 1 bottom plate 11 of drying tower and one anti-
It answers kettle 9 to be connected, excipient feed pipe 91 and PH regulator feed pipe 92 is additionally provided on reaction kettle 9.
The conduit 21 is equipped with a booster pump 23, and the gas-guide tube 31 is equipped with an air pump 33, air pump 33 and helium
Helium purification device 34 is additionally provided on gas-guide tube 31 between gas storage box 32.
The filter device 81 includes mounting plate 82, and 82 edge of mounting plate is fixed on 1 top plate 13 of drying tower, mounting plate 82
Middle part is equipped with interlayer, and microfiltration membranes 83 and ultrafiltration membrane 84 are equipped in interlayer, and the ultrafiltration membrane 84 is arranged above microfiltration membranes 83, is pacifying
Loading board 82 is equipped with several through-holes.
1 outer wall of drying tower is equipped with PLC controller 9, and the booster pump 23, air pump 33, the first vacuum pump 41, second are true
Sky pump 72 controls its opening and closing by PLC controller 9, and the air nozzle is close to guide shell upper surface.
In the present embodiment, air nozzle setting is in drying tower side plate medium position, and the high temperature helium gas pycnometer of ejection is much smaller than sky
Gas, therefore high temperature helium can rise automatically along drying tower, contact with the caspofungin acetate droplet sprayed at top plate, carry out hot friendship
It changes, after heat exchange, the organic solvent and helium density of vaporization are much smaller than caspofungin acetate particle, thus organic solvent
Upper layer is floated on helium, closer to the gas gathering mask on top plate, when starting the pumping of the first vacuum pump, organic solvent and helium quilt
Preferential extraction, the air pressure decline in drying tower, while the caspofungin acetate particle to suspend also with rising at filter device,
It is obstructed by filter device, the first vacuum pump is closed when air pressure drops to certain value, while being passed through high temperature helium and vapor, by
It is moved from bottom to top in high temperature helium and vapor, therefore caspofungin acetate particle continues the progress that suspends under airflow influence
Reaction and heat exchange, in whole process, caspofungin acetate particle is in suspension in the gas flow always or collects in filtering dress
Neighbouring state is set, only helium, vapor make-and-break time and the first vacuum pump opening/closing time need to be adjusted, without it
His structure such as filler etc., can make caspofungin acetate particle be chronically at suspended dispersion, be conducive to heat exchange and hydration is made
Abundant progress, and equipment cost is reduced, the caspofungin acetate after being conducive to drying smoothly collects downwards into next step
Process.
Above-described specific embodiment has carried out further the purpose of the present invention, technical scheme and beneficial effects
It is described in detail, it should be understood that being not intended to limit the present invention the foregoing is merely a specific embodiment of the invention
Protection scope, all within the spirits and principles of the present invention, any modification, equivalent substitution, improvement and etc. done should all include
Within protection scope of the present invention.
Claims (8)
1. a kind of manufacturing method of injection caspofungin acetate, which comprises the following steps:
1) Caspofungin solution is prepared by initial feed of Pneumocandin B0, acetic acid is added and obtains caspofungin acetate solution；
2) caspofungin acetate solution is passed through drying tower (1) to be dried in vacuo, is removed organic molten in caspofungin acetate
Agent；
3) the resulting caspofungin acetate of step 2) is obtained into injection caspofungin acetate through dissolution, ultrafiltration, freeze-drying.
2. a kind of manufacturing method of injection caspofungin acetate according to claim 1, which is characterized in that the step
2) in, vacuum drying process includes the following steps；
21) caspofungin acetate solution is sprayed into drying tower (1) through atomizer, forms caspofungin acetate droplet, simultaneously
It is passed through high temperature helium into drying tower (1) and carries out heat exchange；
22) stop being passed through caspofungin acetate solution and high temperature helium, then utilize the first vacuum pump (41) extraction drying tower (1)
The organic solvent of helium and vaporization in inner cavity；
23) the first vacuum pump (41) are closed, continues to be filled with high temperature helium into drying tower (1), while being filled with vapor, drying tower
(1) after interior air pressure and the external world are consistent, stopping is filled with high temperature helium and vapor, is then turned on the first vacuum pump (41) extraction drying
The organic solvent of helium and vaporization in tower (1) inner cavity；
24) caspofungin acetate particle is obtained after repeating step 23) 1-4 times, caspofungin acetate particle is concentrated on into a collection
In hopper (7), pure water is added and is configured to caspofungin acetate concentrated solution；
25) Material collecting box for harvesting (7) is vacuumized using the second vacuum pump (72), dry caspofungin acetate concentrated solution, after obtaining purification
Caspofungin acetate.
3. a kind of manufacturing method of injection caspofungin acetate according to claim 1, which is characterized in that the step
3) in, caspofungin acetate dissolution, ultrafiltration, freeze-drying specifically comprises the processes of:
31) excipient and PH regulator are added in a reaction kettle, are then added water for injection, after stirring and dissolving, will be made
Caspofungin acetate be added reaction kettle, stirring and dissolving；
32) mixture solution obtained by step 31) is subjected under low temperature, hyperbaric environment after reaction kettle taking-up ultrafiltration, then will produced
Object bottling, freeze-drying.
4. a kind of manufacturing method of injection caspofungin acetate according to claim 2, which is characterized in that the step
22) it in, after stopping is passed through caspofungin acetate solution and high temperature helium, needs to caspofungin acetate droplet and high temperature helium heat
After exchange reaction continues 1-3min, having for the helium and vaporization in the first vacuum pump (41) extraction drying tower (1) inner cavity is recycled
Solvent.
5. a kind of manufacturing method of injection caspofungin acetate according to claim 2, which is characterized in that the step
23) it in, after stopping is filled with high temperature helium and vapor, needs to react to caspofungin acetate particle with vapor, high temperature helium
After continuing 2-4min, the organic solvent of the helium and vaporization that are then turned in the first vacuum pump (41) extraction drying tower (1) inner cavity.
6. a kind of manufacturing method of injection caspofungin acetate according to claim 2, which is characterized in that the step
22) in, pipeline one (42) is entered by the organic solvent of helium and vaporization that the first vacuum pump (41) are extracted out, outside through pipeline one (42)
It is entered in a gas-liquid separation device (43) after condensing unit (5) cooling of wall, organic solvent pre-cooling liquefaction, helium enters one
In the pipeline two (44) that root is connected with gas-liquid separation device (43), pipeline two (44) connects a helium storage box (32), helium
The helium of storage box (32) use storage injection drying tower (1) inner cavity.
7. a kind of manufacturing method of injection caspofungin acetate according to claim 6, which is characterized in that the step
23) in, vapor obtains after heating pure water by a water tank (6), and the condensing unit (5) is cold using pure water as coolant liquid
But entered in water tank (6) after liquid heat exchange by pipeline three (51), water tank (6) by the pipeline five (62) with valve with
Material collecting box for harvesting (7) is connected.
8. a kind of manufacturing method of injection caspofungin acetate according to claim 2, which is characterized in that the step
22) in, the organic solvent using helium and vaporization in the first vacuum pump (41) extraction drying tower (1) inner cavity is by one and dry
The exhaust tube (4) of dry tower (1) top plate (13) connection is realized, filter device, mistake are equipped between exhaust tube (4) and drying tower (1) inner cavity
It filters and is equipped with microfiltration membranes (83) and/or ultrafiltration membrane (84) in device.
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Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1616910A (en) * | 2004-11-05 | 2005-05-18 | 刘贤英 | Vacuum spray drying method for liquid material and vacuum continuous spray drying machine |
| WO2010008493A2 (en) * | 2008-06-25 | 2010-01-21 | Teva Gyógyszergyár Zártkörüen Müködö Részvénytársaság | Processes for preparing high purity aza cyclohexapeptides |
| CN102488886A (en) * | 2011-09-26 | 2012-06-13 | 上海天伟生物制药有限公司 | Caspofungin preparation with low impuritycontent and preparation method and application thereof |
| CN102746384A (en) * | 2011-04-22 | 2012-10-24 | 上海天伟生物制药有限公司 | High purity caspofungin or its salt and its preparation method and application |
| CN107178968A (en) * | 2017-06-13 | 2017-09-19 | 江苏恒瑞医药股份有限公司 | A kind of drying device |
| CN108329377A (en) * | 2017-01-20 | 2018-07-27 | 浙江医药股份有限公司新昌制药厂 | Caspofungin acetate or its salt of a kind of high-purity and preparation method thereof |
-
2018
- 2018-12-26 CN CN201811598506.1A patent/CN109394707A/en active Pending
Patent Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1616910A (en) * | 2004-11-05 | 2005-05-18 | 刘贤英 | Vacuum spray drying method for liquid material and vacuum continuous spray drying machine |
| WO2010008493A2 (en) * | 2008-06-25 | 2010-01-21 | Teva Gyógyszergyár Zártkörüen Müködö Részvénytársaság | Processes for preparing high purity aza cyclohexapeptides |
| CN102746384A (en) * | 2011-04-22 | 2012-10-24 | 上海天伟生物制药有限公司 | High purity caspofungin or its salt and its preparation method and application |
| CN102488886A (en) * | 2011-09-26 | 2012-06-13 | 上海天伟生物制药有限公司 | Caspofungin preparation with low impuritycontent and preparation method and application thereof |
| CN108329377A (en) * | 2017-01-20 | 2018-07-27 | 浙江医药股份有限公司新昌制药厂 | Caspofungin acetate or its salt of a kind of high-purity and preparation method thereof |
| CN107178968A (en) * | 2017-06-13 | 2017-09-19 | 江苏恒瑞医药股份有限公司 | A kind of drying device |
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