CN108653213A - A kind of florfenicol powder and preparation method thereof - Google Patents
A kind of florfenicol powder and preparation method thereof Download PDFInfo
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- CN108653213A CN108653213A CN201810567373.5A CN201810567373A CN108653213A CN 108653213 A CN108653213 A CN 108653213A CN 201810567373 A CN201810567373 A CN 201810567373A CN 108653213 A CN108653213 A CN 108653213A
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- A—HUMAN NECESSITIES
- 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
- A61K9/141—Intimate drug-carrier mixtures characterised by the carrier, e.g. ordered mixtures, adsorbates, solid solutions, eutectica, co-dried, co-solubilised, co-kneaded, co-milled, co-ground products, co-precipitates, co-evaporates, co-extrudates, co-melts; Drug nanoparticles with adsorbed surface modifiers
- A61K9/145—Intimate drug-carrier mixtures characterised by the carrier, e.g. ordered mixtures, adsorbates, solid solutions, eutectica, co-dried, co-solubilised, co-kneaded, co-milled, co-ground products, co-precipitates, co-evaporates, co-extrudates, co-melts; Drug nanoparticles with adsorbed surface modifiers with organic compounds
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- 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
- A61K31/16—Amides, e.g. hydroxamic acids
- A61K31/165—Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
- A61K47/69—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit
- A61K47/6949—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit inclusion complexes, e.g. clathrates, cavitates or fullerenes
- A61K47/6951—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit inclusion complexes, e.g. clathrates, cavitates or fullerenes using cyclodextrin
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- 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
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Abstract
The present invention discloses a kind of florfenicol powder and preparation method thereof, including following mass fraction than component：20 25 parts of Florfenicol, inclusion agents 72 76.9%, dopamine 1.2 1.8%, 0.8 1 parts of dispersant, 0.5 0.8 parts of cosolvent.Florfenicol powder disclosed by the invention and preparation method thereof, pass through molecule inclusion technology, solve the problems, such as that Florfenicol is undissolved in water, greatly improve the bioavilability of product, common centrifugal spray handicraft product heap density is improved by the improvement of technological parameter simultaneously, so that product heap density has been reached and is more suitable for Feed Enterprise and cultivates the level that terminal uses, while improving product mobility, packaging material usage amount is saved, significant economic results in society are created.
Description
Technical field
The invention belongs to field of veterinary medicine preparation, more particularly, to a kind of florfenicol powder and preparation method thereof.
Background technology
Florfenicol is also known as Florfenicol, is a kind of excellent animal specific broad-spectrum antibiotic, has has a broad antifungal spectrum, inhales
It keeps well, be distributed the features such as wide, safe and efficient in vivo, be especially a cancellation the shortcomings that chloramphenicol destroys hemopoietic function of bone marrow, without latent
Induced aplastic anemia, teratogenesis, carcinogenic and mutagenesis.The poultry being widely used on veterinary clinic caused by sensitive bacteria
The treatment of bacterial disease in poultry, and significant effect, no residual chloromycetin problem, are not likely to produce drug resistance, be Thiamphenicol most
Good substitute.But Florfenicol raw material is almost insoluble in water, and common process product bioavilability is low, seriously affects clinical fortune
With.Therefore, the maximum technical barrier of florfenicol formulations is to improve product solubility in water, and formulation products are in water not
Molten, can not especially drink water use on poultry.Even if in addition often heap density is very low for conventional water-soluble formulation products, cause
Inconvenient for use and drug waste, threatening environment safety.Secondly, the usual rate of release of florfenicol formulations is very fast, and then drug
Action time is shorter.So improving the solubility of florfenicol formulations in water, extend the rate of release of drug, for improving
Its bioavilability and expansion clinical application range are of great significance.
The insoluble drugs such as current Florfenicol solve the problems, such as that the bad most common measure of clinical application effect is to add
Add cosolvent or solubilizer and prepare dry suspensoid agent, product bioavilability can be improved in this to a certain extent, but cannot solve
Root problem.A kind of florfenicol soluble powder disclosed in Publication No. CN105055319A and preparation method thereof, to moor Lip river sand
Nurse 188 and PVPk30 are cosolvent, and betadex and HYDROXYPROPYL BETA-CYCLODEXTRIN are carrier, and production technology is relatively simple,
Product water solubility is improved, but PLURONICS F87 and the PVPk30 market prices are relatively high, and additive amount is in 5%-10%,
The product cost of raw material is high, is unfavorable for enterprise's cost efficiency.For another example Publication No. CN105477642A discloses a kind of high biology profit
The composition and preparation method thereof of expenditure Florfenicol, with sodium carboxymethylcellulose, methylcellulose, Carbomer971 p, poly- dimension
Ketone, Arabic gum, sodium alginate etc. are sorbefacient, and betadex is carrier, are given birth to using centrifugal spray or lyophilized technique
Production.Even if the sorbefacients such as involved sodium carboxymethylcellulose, methylcellulose, sodium alginate are in hot water in the patent formulation
Middle rate of dispersion is also very slow, and additive amount, 10% or more, expansion multiple is larger, and production needs a large amount of water, and production capacity is low, cost
It is high.Furthermore such sorbefacient will seriously affect dispersion, solution rate and the rate of release of product in water, and Clinical practice is not
Just.
Invention content
The present invention for overcome the deficiencies in the prior art, provides that a kind of drug releasing rate is slow, solubility is high, heap density is suitable
Suitable florfenicol powder and preparation method thereof.
To achieve the goals above, the present invention uses following technical scheme：A kind of florfenicol powder, including following quality point
The component of number ratio：Florfenicol 20-25%, inclusion agents 72-76.9%, dopamine 1.2-1.8%, dispersant 0.8-1% dive molten
Agent 0.5-0.8%.
Use inclusion agents in the present invention, realize the stability of material by molecule inclusion technology, it is non-degradable it is non-discolouring not
Caking, high degree improve properties of product.
Further, the inclusion agents are the mixture of betadex and HYDROXYPROPYL BETA-CYCLODEXTRIN.
Further, the mass ratio of the betadex and HYDROXYPROPYL BETA-CYCLODEXTRIN is 5:1.
Further, the dispersant is the combination of one or both of propylene glycol block polyether, poly glycol monomethyl ether.
Further, the cosolvent is the combination of one or more of dimethyl sulfoxide (DMSO), sodium succinate, glycerine.
The invention also discloses the preparation methods of the florfenicol powder, include the following steps：
A, to weigh Florfenicol, inclusion agents, dispersant and cosolvent respectively by the mass fraction percentage spare；
B, dopamine is put into distilled water, stirring is configured to the dopamine solution of 8g/L, later adds Florfenicol
Enter into dopamine solution, mixed liquor is obtained after stirring and dissolving；Mixed liquor and inclusion agents are uniformly mixed later, liquid is heated
It is stirred continuously simultaneously to 80~83 DEG C and can be obtained molecule inclusion liquid, ratio of water to material 2:1；
C, when molecule inclusion liquid temperature in step b is stablized in 80~83 DEG C of ranges, input dispersant, cosolvent, clarification
Stirring heat preservation 1h afterwards, then carries out it centrifugal spray drying processing using drying machine with centrifugal spray, crosses 80 mesh sieve, you can obtain
Finished product.
Further, in the step c during centrifugal spray drying by the size controlling of florfenicol powder 120~
160μm。
Further, the inlet air temperature in the step c when centrifugal spray drying is 175~180 DEG C, leaving air temp 90
±2℃。
The present invention uses molecule inclusion technology in preparation process so that molecular state can be presented in material, with molecularity
State is being completely dissolved in water, and solubility is high, and water-soluble ability is strong, efficiently solves the problems, such as that the water-soluble speed of traditional pulvis is slow；
Dopamine is added, by the compound of dopamine and florfenicol powder, effectively slows down the rate of release of drug, and then extend
The pharmaceutically-active time plays the role of long-acting, sustained release, improves therapeutic effect；Secondly, pulvis upon dissolution, can be realized
It is long placed in no precipitation, the use demand of poultry drinking-water and domestic animal spice can be met simultaneously；Powder processed is carried out by the way of centrifugal spray,
Efficiently solving the problems, such as Florfenicol, indissoluble solution and low bulk density Clinical practice are limited in water, the product heap being prepared
Density is high, and then effectively enhances the water solubility of product, has not only solved the problems, such as that water-soluble speed was slow, but also solve product heap density
Low problem, avoiding conventional water-soluble Florfenicol, routinely the low density phenomenon of production heap occurs, and has prodigious technology excellent
Gesture；Secondly, the stability of drug character is improved by molecule inclusion technology so that pulvis it is non-degradable it is non-discolouring do not lump, no
Easily there is rotten situation, raising pulvis is edible to obtain safety.
The present invention uses centrifugal spray technique productions florfenicol powder, and it is convenient that technological approaches is realized, production capacity is high, at low cost,
It is produced suitable for Industrialization；This product solubility is high, dissolving is rapid, heap appropriate density, high production capacity low cost Florfenicol
Preparation facilitates Clinical practice, and being truly realized cost efficiency in cultivation terminal is of great significance.
In conclusion the present invention has the following advantages：By molecule inclusion technology, it is insoluble in water to solve Florfenicol
The problem of solution, greatly improves the bioavilability of product, while improving common centrifugation spray by the improvement of technological parameter
Mist handicraft product heap density makes product heap density reach and is more suitable for Feed Enterprise and cultivates the level that terminal uses, carries simultaneously
High product mobility, saves packaging material usage amount.
Description of the drawings
After Fig. 1 takes 2 drug of experimental group, control group 1 and control group orally for chicken single dose (30mg.kg-1) in control experiment 2
The relational graph of blood mass concentration and time.
Fig. 2 be in control experiment 3 after 1 drug of pig spice feeding Florfenicol original powder and embodiment blood mass concentration and when
Between relational graph.
Fig. 3 is Florfenicol in control experiment 4 in rat vivo medicine concentration-time plot.
Fig. 4 is the structural schematic diagram of the drying machine with centrifugal spray in the present invention.
Fig. 5 is the lateral partial structurtes sectional view of the drying machine with centrifugal spray in the present invention.
Fig. 6 is enlarged drawing at A in Fig. 4.
Fig. 7 is enlarged drawing at A in Fig. 5.
Fig. 8 is enlarged drawing at B in Fig. 5
Sectional view when Fig. 9 is shaft and connection axis connection in the drying machine with centrifugal spray in the present invention.
Figure 10 is the sectional view of condenser pipe in the present invention.
Figure 11 is the scheme of installation of catch basin in the present invention.
Specific implementation mode
In order to make those skilled in the art be better understood from the present invention program, below in conjunction in the embodiment of the present invention
Attached drawing, technical solution in the embodiment of the present invention carry out clear, complete description.
Embodiment 1：
If producing 100kg florfenicol powders, comprise the steps of：
(1) Florfenicol 20kg is weighed, betadex and HYDROXYPROPYL BETA-CYCLODEXTRIN are respectively 64.4kg and 12.3kg
(based on active ingredient), dopamine 1.8kg, propylene glycol block polyether 1kg, dimethyl sulfoxide (DMSO) 0.5kg are spare；
(2) dopamine is put into distilled water, stirring is configured to the dopamine solution of 8g/L, later adds Florfenicol
Enter into dopamine solution, mixed liquor is obtained after stirring and dissolving；Mixed liquor, betadex and hydroxypropyl times his ring are pasted later
Essence is uniformly mixed, and liquid is heated to 83 DEG C while being stirred continuously to can be obtained molecule inclusion liquid, ratio of water to material 2:1；
(3) when molecule inclusion liquid temperature in step (2) is stablized in 83 DEG C of ranges, input propylene glycol block polyether, diformazan
Base sulfoxide, stirring heat preservation 1h, then carries out centrifugal spray drying processing using drying machine with centrifugal spray to it after clarification；Further
, by atomizing disk variable frequency adjustment to 15hz, the particle size range of powder material obtained is made to control at 120 μm, then by material mistake
80 mesh sieve is to get to florfenicol powder.
Specifically, as shown in Fig. 4-11, the drying machine with centrifugal spray includes tower body 1, doing in the tower body 1
Dry chamber 11 and percussion device for hitting the tower body 1,11 top of the drying chamber be equipped with centrifugal atomizing disk 3, hot blast pipe 4 and
For the condensing unit of condensed steam, 4 outlet end of the hot blast pipe is equipped with outlet nozzle 43, and the percussion device includes support
Frame 2, on support frame as described above and more shafts 6 being sequentially connected successively, the cam being respectively arranged in the more shafts 6
61, multiple fixed blocks 7 on 1 outer wall of the tower body, the active tunnel 71 on the fixed block 7, one end are inserted in
In the active tunnel 71 with the matched ram 8 of the cam, the return unit 9 being sheathed on the ram 8 and be used for
The driving part of driving more shafts 6 rotation, the return unit 9 is spring, 9 one end of return unit and 7 phase of fixed block
Even, the other end is connected with ram 8；The more shafts 6 are enclosed outside the tower body 1, when liquid is via centrifugal atomizing disk 3
It is atomized into after droplet sprays, drop and hot-air current contacting out of hot blast pipe 4, the moisture in drop is evaporated, in turn
Florfenicol powder preparation is obtained, however since the Florfenicol powder preparation not being completely dried in the drying process easily adheres to
Blocking situation is bonded to powder formulation occur on to the inner wall of drying chamber, and coking easily occurs, to influence powder
The quality of preparation；And the percussion device of 1 outer wall of tower body can be hit by setting, so that tower body 1 vibrates, and then will
The material vibrating being attached on 11 inner wall of drying chamber gets off, and effectively prevents the blocking problem of powder bonding；And due in liquid
Moisture evaporated by the hot-air in hot blast pipe 4 so that be full of this large amount of vapor in drying chamber 11, be unfavorable for florfenicol powder
The drying at end, so vapor is condensed into water again by the way that condensing unit is arranged, then by water collection export to drying chamber 11 it
Outside, both play the role of saving water resource, in turn ensure the drying in drying chamber 11 so that Florfenicol powder obtained is more
Add drying, is not easy to bond blocking.
Specifically, support frame as described above 2 be disposed around metal ring on 1 outer wall of tower body, further, the metal ring and
There is certain gap, which is evenly arranged with 4 supports along the circumferentially-spaced of annulus between 1 outer wall of tower body
Foot 25,25 bottom end of the support leg are fixed by screws on ground, since supporting rack is no and tower body is directly connected to, and then are worked as
When tower body vibrates, so the vibration effect that supporting rack 2 is subject to is smaller.The more shafts 6 are arranged in the metal ring
Upper surface, the number of the shaft 6 is 8 in this present embodiment, and described 8 shafts 6 are in the octagon with an opening
Shape is disposed around outside tower body 1, and it is 8 pieces that the fixed block 7, which is made of metal material its number also, and described 8 pieces of fixed blocks 7 are along tower
External wall is provided at circumferentially spaced, and the active tunnel 71 is horizontally disposed, and the ram 8 is made of metal material,
It includes cylindrical portion and globular part, and described cylindrical portion one end is plugged in the active tunnel 71 of fixed block 7, and the cam 61 is turning
It can be in contact with globular part when dynamic and globular part is pushed to be moved to close to the direction of fixed block 7, and then cylindrical portion is pushed to hit
1 outer wall of tower body is so that tower body 1 vibrates, further, on support frame as described above 2 corresponding to the position of every shaft 6 at
Two first bearing seats 10 are respectively equipped with, every 6 left and right ends of shaft are threaded through respectively in the first bearing seat 10, such as Fig. 5
It is shown, we define be arranged 1 directly to the right of tower body shaft 6 be first shaft, and define using first shaft as starting point
Other 7 shafts set gradually in the direction of the clock are respectively second, third root, the 4th, the 5th, the six roots of sensation,
Seven, the 8th shaft when 8 shafts rotate respectively under the driving effect of driving part, the cam in shaft 6 is set
61 can rotate together with shaft 6 and ram 8 is pushed constantly to hit 1 outer wall of tower body, so that tower body can shake
It is dynamic, since 8 shafts are disposed around outside tower body, and then when 8 shafts rotate, can be hit on 8 positions of tower body outer wall
Tower body will can more effectively be attached to improve the percussion device Oscillation Amplitude that tower body occurs when hitting tower body
Material vibrating on dry cavity wall gets off, and is sequentially connected successively additionally, due to more shafts, and more shafts are being installed
When ensure that cam under the same time in every shaft relative to the position of ram and different, i.e., is not institute under the same time
The cam stated can push ram to strike the outer wall of tower body 1, i.e. 8 rams are to hit tower body in intermittent state
, so that 8 cams in 8 shafts can push corresponding ram to hit tower body outer wall respectively whithin a period of time, it can
To carrying out successively eight shocks at eight different positions of tower body respectively, the vibration area of tower body, and this eight times are not only expanded
The vibration wave generated after shock can be overlapped mutually, and then the further vibrating effect for enhancing tower body, be further convenient for
The material vibrating being attached on dry cavity wall is got off.
Further, it is realized and is sequentially connected by a drive mechanism between adjacent two shaft 6, specifically, described
Drive mechanism includes the mounting base 21 being arranged on supporting rack 2, is set in the mounting base 21 and intermeshing two first umbrella
Gear 22, supplies described shaft one end to be inserted at the connecting shaft 23 on first bevel gear in the connecting shaft 23
Inserting groove 231, the rotation stop groove 232 on 231 inner wall of the inserting groove are set in the shaft 6 and 232 phase of the rotation stop groove
The anti-rotation block 61 of cooperation and in the mounting base 21 and 23 matched second bearing seat 24 of the connecting shaft；The rotation stop
There is certain gap, the diameter of the connecting shaft 6 to be less than the maximum of the first bevel gear 22 between 232 inner wall of block 61 and rotation stop groove
Diameter；By being respectively set connecting shaft 23 on two intermeshing first bevel gears, and in mounting base 21 setting with it is described
The second bearing seat 24 of connecting shaft interference fit, and then can ensure when supporting rack 2 vibrates, two first bevel gears according to
Old to keep intermeshing state, in addition shaft passes through anti-rotation block and the mating reality of rotation stop groove being arranged in connecting shaft
The rotation stop cooperation of existing two shafts and connecting shaft, and due to having certain gap, Jin Er between anti-rotation block and rotation stop groove inner wall
When cam in shaft pushes ram 8 to hit tower body outer wall and vibrate, due to the presence in the gap make shaft with
While cooperation certain offset can also occur relative to connecting shaft for connecting shaft rotation stop, that is, the vibration in shaft is prevented to involve
Onto the first bevel gear, to which two bevel gears ensured in mounting base can remain the state of engagement, and then 8 are ensure that
Shaft can realize drive connection always.
Further, the driving component includes the transmission shaft 63 being sequentially connected with a wherein shaft 6 and for driving
The driving motor 64 that the dynamic transmission shaft 63 rotates, specifically, the driving motor 64 is the general electricity directly bought in the market
Machine, structure and operation principle are that therefore not to repeat here for the prior art, and the driving motor 64 is mounted on supporting rack 2, described
Transmission shaft 63 is by the output axis connection of shaft coupling and driving motor 64, on one end of the separate driving motor of the transmission shaft 63
If there are one the second bevel gear 65, set that there are one the second bevel gears on the described one end of first shaft far from the first bevel gear 62
65, two the second bevel gear 65 intermeshings；And then when driving motor works, 8 shafts 6 can finally be driven to turn together
It is dynamic, eight different locations of tower body can be hit by a driving motor and bring it about 8 vibrations, to subtract
Lack energy consumption, reduces production cost.
Preferably, the percussion device is two groups, described two groups of percussion devices in setting up and down on the outer wall of tower body,
By the way that percussion device is set as two groups, the rum point to tower body is further increased, i.e., further expands the vibration of tower body
Range is vibrated to improve the vibrating effect of tower body conducive to by the material being attached on dry cavity wall completely.
Further, the centrifugal atomizing disk 3 is connected by conveying pipeline 31 with a liquid storing barrel 32, on the conveying pipeline 31
It is provided with charging pump 33, the centrifugal atomizing disk 3 and charging pump 33 all can directly be bought from the market, therefore this will not be repeated here,
When feed liquid is placed in liquid storing barrel, by charging pump can by feed liquid extract out and via centrifugal atomizing disk be ejected in drying chamber with
Hot-air current contacting, and then realize drying purpose.
Further, the hot blast pipe 4 is connected with a heater box 41, and heating wire is equipped in the heater box 41, described
41 side of heater box is equipped with air blower 42, and then when air blower 42 works can be transported to the hot-air in heater box 41 dry
It is in contact in dry chamber 11 and then with the drop sprayed through centrifugal atomizing disk and desiccation is played to it.
Further, the condensing unit includes the cold plate 5 for being set to 1 top of the tower body, is set in the cold plate 5
Condenser pipe 51, the conduit 52 that one end is connected with the condenser pipe 51, the condensation liquid bath 53 being connected with 52 other end of the conduit
And the water pump 54 on conduit 52；The water pump 54 can directly commercially, therefore this will not be repeated here；In the present embodiment
Condensate liquid be water；By the way that condensing unit is arranged so that the vapor of hot blast pipe evaporation droplet formation encounters condensation after rising
Device and be condensed into water again, then the obtained water of condensation is collected and is exported to except drying chamber, the water condensed can also
It is reused for the making of Florfenicol liquid, has both played the role of saving water resource, has in turn ensured the drying in drying chamber, just
In the making of Florfenicol powder so that Florfenicol powder is not easy to bond blocking.
When work, water is pumped into the water inlet pipe 521 in conduit 52 by water pump 54, the water inlet of water inlet pipe 521 and condenser pipe 51
Mouth 511 is connected, and water flows out after flowing a circle in the condenser pipe 51 of coiling from water outlet 512, is reentered through outlet pipe 522
Cooling in liquid bath 53 is condensed, the circulating condensing effect of a condensate liquid has been thusly-formed, has ensured the operation of condensing unit；Work as liquid
After being atomized into droplet ejection in centrifugal atomizing disk 3, drop and the hot-air current contacting out of hot blast pipe 4 so that liquid
Moisture in drop is evaporated to vapor, and vapor rising encounters cold plate 5, is re-cooled and is attached to cold plate for droplet
On 5, with the vibration of the increase and drying chamber 11 of droplet, diversion trench of the droplet on cold plate 5 slides to catch basin
In 55, droplet flows into after collecting in catch basin 55 in the catheter 56 with funnel-shaped opening, and bucket is flowed into through catheter 56
In 57, the recycling of water resource is realized；By the condenser pipe that coiling is arranged so that entire cold plate all has condensation effect,
Pass through the cooperation of water pump and conduit so that the condensate circulation flowing in condenser pipe ensure that condensate liquid is in low temperature shape always
State, and then ensure that the condensation effect of condensing unit；Pass through and inlet and outlet pipes are set so that condensate liquid in condenser pipe will not be because of
Condensed steam and the excessively high forfeiture condensation effect that heats up, and then ensure that the condensation effect of condensing unit；Pass through setting for catch basin
It sets so that the droplet that condensing unit condenses is collected, then enters bucket by catheter, and obtained condensed water can weigh
It is multiple to utilize, save water resource.
Further, the tower body 1 is equipped with the conical discharge port 12 that is connected with the drying chamber 11, and then after drying
Florfenicol powder preparation can be expelled directly out from the discharge port.
Embodiment 2：
If producing 100kg florfenicol powders, comprise the steps of：
(1) Florfenicol 20kg is weighed, betadex and HYDROXYPROPYL BETA-CYCLODEXTRIN are respectively 64.4kg and 12.3kg
(based on active ingredient), dopamine 1.8kg, propylene glycol block polyether and each 0.5kg of poly glycol monomethyl ether, sodium succinate and sweet
Oily each 0.3kg, it is spare；
(2) dopamine is put into distilled water, stirring is configured to the dopamine solution of 8g/L, later adds Florfenicol
Enter into dopamine solution, mixed liquor is obtained after stirring and dissolving；Later by mixed liquor, betadex, hydroxypropyl times he paste ring
Essence is uniformly mixed, and liquid is heated to 81 DEG C while being stirred continuously to can be obtained molecule inclusion liquid, ratio of water to material 2:1；
(3) when molecule inclusion liquid temperature in step (2) is stablized in 81 DEG C of ranges, input propylene glycol block polyether, poly- second
Glycol monomethyl ether, sodium succinate and glycerine, stirring heat preservation 1h, then centrifuges it using drying machine with centrifugal spray after clarification
Spray drying treatment；Further, by atomizing disk variable frequency adjustment to 20hz, the particle size range control of powder material obtained is made to exist
140 μm, material is then crossed into 80 mesh sieve to get to florfenicol powder.
Embodiment 3：
If producing 100kg florfenicol powders, comprise the steps of：
Florfenicol 25kg is weighed, betadex and HYDROXYPROPYL BETA-CYCLODEXTRIN are respectively that 60.2kg and 11.8kg (are pressed
Active ingredient meter), dopamine 1.2kg, propylene glycol block polyether and each 0.5kg of poly glycol monomethyl ether, dimethyl sulfoxide (DMSO) and sweet
Oily each 0.4kg, it is spare；
(2) dopamine is put into distilled water, stirring is configured to the dopamine solution of 8g/L, later adds Florfenicol
Enter into dopamine solution, mixed liquor is obtained after stirring and dissolving；Later by mixed liquor, betadex, hydroxypropyl times he paste ring
Essence is uniformly mixed, and liquid is heated to 80 DEG C while being stirred continuously to can be obtained molecule inclusion liquid, ratio of water to material 2:1；
(3) when molecule inclusion liquid temperature in step (2) is stablized in 80 DEG C of ranges, input propylene glycol block polyether, poly- second
Glycol monomethyl ether, sodium succinate and glycerine, stirring heat preservation 1h, then centrifuges it using drying machine with centrifugal spray after clarification
Spray drying treatment；Further, by atomizing disk variable frequency adjustment to 15hz, the particle size range control of powder material obtained is made to exist
120 μm, material is then crossed into 80 mesh sieve to get to florfenicol powder.
Embodiment 4：
If producing 100kg florfenicol powders, comprise the steps of：
Florfenicol 25kg is weighed, betadex and HYDROXYPROPYL BETA-CYCLODEXTRIN are respectively that 60.2kg and 11.8kg (are pressed
Active ingredient meter), dopamine 1.2kg, poly glycol monomethyl ether 1kg, sodium succinate and glycerine each 0.4kg are spare；
(2) dopamine is put into distilled water, stirring is configured to the dopamine solution of 8g/L, later adds Florfenicol
Enter into dopamine solution, mixed liquor is obtained after stirring and dissolving；Later by mixed liquor, betadex, hydroxypropyl times he paste ring
Essence is uniformly mixed, and liquid is heated to 83 DEG C while being stirred continuously to can be obtained molecule inclusion liquid, ratio of water to material 2:1；
(3) when molecule inclusion liquid temperature in step (2) is stablized in 83 DEG C of ranges, input propylene glycol block polyether, poly- second
Glycol monomethyl ether, sodium succinate and glycerine, stirring heat preservation 1h, then centrifuges it using drying machine with centrifugal spray after clarification
Spray drying treatment；Further, by atomizing disk variable frequency adjustment to 25hz, the particle size range control of powder material obtained is made to exist
160 μm, material is then crossed into 80 mesh sieve to get to florfenicol powder.
Above example be by the technology implementation process certain embodiments lifted more effective and being illustrated for illustrating the present invention and
, the limitation carried out to the application range of the present invention is not it.As long as what is done on the basis of the present invention is not significantly
Improvement all can be considered the row in protection scope of the present invention.
Control experiment 1：
Florfenicol powder produced by the invention is carried out with city's pin product in solubility, solution rate, solute effect etc.
Experimental Comparison.
Experimental group：Florfenicol powder (the specification that embodiment 1 and embodiment 2 produce：100:20).
Control group：Florfenicol powder 1 is sold in city and 2 (specification of florfenicol powder is sold in city：100:20).
Experimental method：
A, 1L normal-temperature waters (25 ± 2 DEG C) are modulated, 200ml normal-temperature waters are respectively contained in 4 250ml beakers of A1, A2, B1, B2, it is standby
With；
B, embodiment 1 and each 3g of 2 florfenicol powder of embodiment (15g/l, 3000ppm) are separately added into A1 and A2 beakers,
Stirring records mixing time until clarification completely；
C, city's pin florfenicol powder 1 and 2 each 3g (15g/l, 3000ppm) is separately added into B1 and B2 beakers, stirring until
Clarification completely records mixing time；
D, above 4 sample heap density are measured respectively, and observe mobility, are compared.
Experimental result：
1 experimental group of table is with control group in solubility, solution rate, solute effect etc. comparing result
It is above-mentioned the experimental results showed that, the florfenicol powder stirring and dissolving time produced by the invention is all within 1min, hence it is evident that
It is faster than the cities Liang Ge pin product；And dissolving clarity highly-water-soluble is up to 15g/l, i.e. 3000ppm, it is not muddy, without floating material and
Precipitation stands 48h and is cooled to 15 DEG C and still clarifies molten, no precipitate completely, and solute effect is good；Product heap density of the present invention
In 0.40g/ml or more, mobility is good, and animal clinical preferably uses.
Control experiment 2：
Florfenicol powder produced by the invention changes feelings with blood concentration of the external two Florfenicol products in chicken body
Condition compares, to judge the bioavilability of different product.
Experimental method：
1, medication and blood sampling time
36 Sanhuang chickens, every chicken single dose are selected to be administered by 30mg.kg-1 (in terms of Florfenicol) spice.Refer to table 1.
(0h) strength venous blood collection about 4mL is as blank control before perfusion.5 after perfusion, 15,30min and 1,2,4,6,8,10,12, it is each for 24 hours
Blood sampling 1 time, take a blood sample about 4mL every time.It places it in the centrifuge tube containing heparin, 3000r/min, centrifugation 10min, separated plasma ,-
It is preserved under the conditions of 20 DEG C, it is to be measured.
Experimental group：1 florfenicol powder of the embodiment of the present invention, specification 100:20
Control group 1：Certain external company's florfenicol powder, specification 100:10
Control group 2：Certain external company's florfenicol powder, specification 100:2
2, blood serum sample pre-processes
It is accurate to pipette plasma sample 0.5mL and be placed in 10mL centrifuge tubes, add 10 μ L of Thiamphenicol internal standard solution (1g.L-1) and
The PES liquid (pH=7.0) of 0.5mL, whirlpool 3min are mixed well.Then 3.0mL ethyl acetate is added, whirlpool 3min is fully mixed
5min is centrifuged after even, draws ethyl acetate supernatant in another test tube.Same method repeats extraction 1 time, merges second twice
Acetoacetic ester extracting solution evaporates into draught cupboard dry.In residue plus 1.0mL mobile phases, whirling motion 1min, ultrasonic 5min, 0.45 μm
After membrane filtration, 25 μ L sample introductions are drawn, measure blood concentration.
Experimental result：
2 chicken single dose of table takes blood concentration (mg.L-1) after 2 drug of experimental group, control group 1 and control group orally.
Chicken single dose (30mg.kg-1) take orally after 2 drug of experimental group, control group 1 and control group blood mass concentration and when
Between relationship, see Fig. 1.
As shown in Table 2, the peak concentration of drug of experimental group, control group 1 and control group 2 is respectively 7.36mg.L-1,6.47mg.L-
1 and 6.37mg.L-1, peak time are respectively 0.25,0.5 and 0.5h, and the area under the drug-time curve being calculated (AUC) is respectively
For 29.0mg.L-1/h, 20.0mg.L-1/h and 22.4mg.L-1/h.
Compare and can be seen that, after single dose takes 2 drug of experimental group, control group 1 and control group orally, the pharmacokinetic parameters of three have
Difference.Peak concentration of drug, the area under the drug-time curve of experimental group are above control group 1 and control group 2, and peak time is below separately
Two groups.Wherein peak concentration of drug is 1.14 and 1.16 times of control group 1 and knob control group 2 respectively, and area under the drug-time curve is respectively
1.45 and 1.29 times.Illustrate florfenicol powder produced by the invention in chicken body up to higher blood concentration, under Drug-time curve
Area bigger can play long-acting.
Control experiment 3：
Efficiently water-soluble Florfenicol product of the invention is probed into compared with original powder, drug is in terms of pharmacokinetics the case where.
Experimental method：
The big pig 18 of selection health, age in days, weight are close, and male and female is fifty-fifty, are randomly divided into 2 groups, every group 9, every group of 3 weights
It is multiple.It routinely raises, free water and feeding.Feed is the full price mash diet without antibacterials.Clinical observation 2 before experiment
Week.16h fasting, only free water before administration, are administered free water and feeding after 6h.Following determination of plasma concentration process is the same as control
Experiment 2.
3 experimental design of table
Experimental result：
The blood mass concentration of pig spice feeding Florfenicol original powder and different time after 1 drug of embodiment is shown in Table 4 and figure
2。
The blood mass concentration mg.L of different time after 4 pig spice feeding Florfenicol original powder of table and 1 drug of embodiment-1
As shown in Table 4, the peak concentration of drug of Florfenicol original powder and fluorine pleasure sweet smell is respectively 2.85mg.L-1And 10.14mg.L-1,
Peak time is 2h, and the area under the drug-time curve (AUC) being calculated is respectively 14.55mg.L-1/ h and 72.78mg.L-1/
h。
Compare and can be seen that, after spice feeds Florfenicol original powder and fluorine pleasure sweet smell, there were significant differences for the pharmacokinetic parameters of the two.
The fragrant peak concentration of drug of fluorine pleasure is 3.56 times of Florfenicol original powder, and area under the drug-time curve is 5.00 times of Florfenicol original powder.
Illustrate the fragrant peak concentration of drug higher of spice feeding fluorine pleasure, area under the drug-time curve bigger, elimination is slower, can play more long-acting
Effect.
Control experiment 4：
The main purpose of pharmacokinetics experiment of the Florfenicol in rat body, this experiment is the different system of research
Influence of the agent method processing to Florfenicol function and effect.
Experimental method：
12 rats are selected in experiment, and every rat gavages Florfenicol original powder respectively with 30mg/kg dosage, the present invention is implemented
1 florfenicol powder of example, certain external renowned company's florfenicol formulations, (0h) acquires blood by femoral artery before rats gavaged administration
Liquid makees blank control.5min, 15min after perfusion, 30min, 1h, 2h, 4h, 6h, 8h, 10h, blood is acquired for 24 hours.It will be collected
Fresh blood sample be placed in heparin sodium centrifuge tube, 3min is centrifuged with 9000r/min, separated plasma is simultaneously stored in -80 DEG C, so
After measure blood concentration.Florfenicol is drawn in rat vivo medicine concentration-time plot, such as Fig. 3.
Test result shows that area is significantly high under the Cmax and drug-time curve of 1 florfenicol powder of the embodiment of the present invention
In Florfenicol original powder and certain external renowned company's florfenicol formulations, show florfenicol powder produced by the invention in rat body
Interior infiltration rate is fast, degree of absorption is significantly higher than Florfenicol original powder and certain external renowned company's product.1 fluorobenzene Buddhist nun of embodiment
Examine half-life period (t1/2) and mean residence time (MRT) of the powder in rat body be also significantly greater than Florfenicol original powder and it is external certain
Renowned company's product shows that florfenicol powder produced by the invention residence time in rat body is longer, is conducive to send out for a long time
Wave its drug effect.
Obviously, described embodiment is only a part of the embodiment of the present invention, instead of all the embodiments.It is based on
Embodiment in the present invention, it is obtained by those of ordinary skill in the art without making creative efforts every other
Embodiment should all belong to the scope of protection of the invention.
Claims (8)
1. a kind of florfenicol powder, it is characterised in that：Including following mass fraction than component：Florfenicol 20-25%, inclusion
Agent 72-76.9%, dopamine 1.2-1.8%, dispersant 0.8-1%, cosolvent 0.5-0.8%.
2. a kind of florfenicol powder according to claim 1, it is characterised in that：The inclusion agents are betadex and hydroxyl
The mixture of propyl betadex.
3. a kind of florfenicol powder according to claim 2, it is characterised in that：The betadex and hydroxypropyl times he
The mass ratio of cyclodextrin is 5:1.
4. a kind of florfenicol powder according to claim 1, it is characterised in that：The dispersant is poly- for propylene glycol block
One or both of ether, poly glycol monomethyl ether combine.
5. a kind of florfenicol powder according to claim 1, it is characterised in that：The cosolvent is dimethyl sulfoxide (DMSO), amber
One or more of Meticortene Solu-Delta-cortef, glycerine combine.
6. a kind of preparation method of florfenicol powder as described in any one in claim 1-5, it is characterised in that：Including following step
Suddenly：
A, to weigh Florfenicol, inclusion agents, dopamine, dispersant and cosolvent respectively by the mass fraction percentage spare；
B, dopamine is put into distilled water, stirring is configured to the dopamine solution of 8g/L, later by Florfenicol be added to
In dopamine solution, mixed liquor is obtained after stirring and dissolving；Mixed liquor and inclusion agents are uniformly mixed later, liquid is heated to 80
~83 DEG C are stirred continuously can be obtained molecule inclusion liquid simultaneously, ratio of water to material 2:1；
C, when molecule inclusion liquid temperature in step b is stablized in 80~83 DEG C of ranges, input dispersant, cosolvent stir after clarification
Heat preservation 1h is mixed, then carries out centrifugal spray drying processing to it using drying machine with centrifugal spray, crosses 80 mesh sieve, you can obtain into
Product.
7. a kind of preparation method of florfenicol powder according to claim 6, it is characterised in that：It is centrifuged in the step c
By the size controlling of florfenicol powder at 120~160 μm in spray-drying process.
8. a kind of preparation method of florfenicol powder according to claim 6, it is characterised in that：It is centrifuged in the step c
Inlet air temperature when spray drying is 175~180 DEG C, and leaving air temp is 90 ± 2 DEG C.
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| CN112121016A (en) * | 2020-10-09 | 2020-12-25 | 清远海贝生物技术有限公司 | Water-soluble florfenicol powder and preparation method thereof |
| CN112716902A (en) * | 2021-02-04 | 2021-04-30 | 广州市和生堂动物药业有限公司 | Florfenicol powder and preparation method thereof |
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