CN108721209A - A kind of azithromycin injection for animals - Google Patents
A kind of azithromycin injection for animals Download PDFInfo
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- CN108721209A CN108721209A CN201810347546.2A CN201810347546A CN108721209A CN 108721209 A CN108721209 A CN 108721209A CN 201810347546 A CN201810347546 A CN 201810347546A CN 108721209 A CN108721209 A CN 108721209A
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- 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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Abstract
The present invention provides a kind of azithromycin injections for animals, belong to medicinal chemistry art.Injection of the present invention comprising active constituent and solvent for injection diethylene glycol monoethyl ether, can in -14 days 1 day delivery of biologically active ingredient or active ingredient；Its long action time, it is possible to reduce administration number of times reduces irritation and oedema situation to a certain extent, increases and uses compliance, and preparation process is simple, easy to operate, stable quality is conducive to apply.
Description
Technical field
The present invention relates to a kind of azithromycin injections for animals, and in particular to it is a kind of for treat livestock and poultry infection Ah. for animals
Miramycin injection, belongs to medicinal chemistry art.
Background technology
Azithromycin is a kind of macrolide antibiotics, can be used for chlamydia pneumoniae, haemophilus influenzae, Shi Fei armies
Skin infection caused by the bacteriums such as group bacterium, catarrh mora bacterium, staphylococcus aureus or streptococcus pneumonia, is secreted at respiratory tract infection
The multi-infections such as urogenital system togetherness dye, for clinically one of common antibacterials.In the animal kingdom, in domestic birds and animals, Ah
Miramycin also has the effects that wider antibacterial, but has no that special azithromycin veterinary formulations, the people listed use Ah at present
Miramycin dosage form is mainly tablet and injection, and wherein injection is mainly venous transfusion agent, generally once a day.Zitromax
Plain venous transfusion agent irritation is stronger, easy tos produce infusion reaction.Therefore, it if these dosage forms are used for animal, is commonly present many
Inconvenience, if irritation is strong, multiple dosing, the problem of bringing poor compliance.In consideration of it, it is necessary to study a kind of low irritant, make
It is long with the time, frequency injection, the compliance azithromycin injection preferably for animals of patient can be reduced.
Invention content
Summary of the invention
The present invention provides a kind of azithromycin injections for animals and preparation method thereof.Injection of the present invention,
Irritation is smaller, long action time, can in -14 days 1 day delivery of biologically active ingredient or active ingredient；Administration can be reduced
Number increases and uses compliance, and preparation process is simple to operation, stable quality, is conducive to apply.Closer, exist
Within the scope of certain dosage, compared to one or more of mixed solvents such as physiological saline, 5% glucose solution, PEG200
As the azithromycin injection of injection solvent, the azithromycin injection in the present invention can largely reduce irritation, from
And significantly reduce pain and oedema situation.
Azithromycin injection for animals provided by the invention, faces the used time comprising active constituent and solvent for injection diethyl
Glycol list ethylether (such as Transcutol V).
Term defines
Term " for animals " refers to that the object that uses of said preparation is animal, including mammal and birds etc., and preferably lactation is dynamic
Object.
Term " injection " refers to the composition (usually hypodermic injection or intramuscular injection) of injectable, after injection medicine
Object is slowly distributed to the systemic circulation system using main body, and in this way, drug can continue in a controlled manner
Delivering.
Term " prodrug " refers to a kind of molecule of no therapeutic activity, it can convert active drugs group by physiological metabolism
Point.
Term " D50 " refers to that the cumulative particle sizes percentile of a sample reaches grain size corresponding when 50%, it
Physical significance is that grain size accounts for 50% more than its particle, and the particle less than it also accounts for 50%.
Term " D90 " refers to that the cumulative particle sizes percentile of a sample reaches grain size corresponding when 90%, it
Physical significance is that grain size accounts for 90% less than its particle.
Detailed description of the invention
The present invention provides a kind of azithromycin injection for animals, can in -14 days 1 day delivery of biologically active ingredient or
Active ingredient, long action time, it is possible to reduce administration number of times, and irritation and oedema situation, energy are reduced to a certain extent
Enough increase uses compliance.
Azithromycin injection for animals provided by the invention delivery of biologically active ingredient or can have in -14 days 1 day
Imitate ingredient.In some embodiments, the azithromycin injection for animals can in -7 days 1 day delivery of biologically active ingredient
Or active ingredient.In some embodiments, the azithromycin injection for animals can in -5 days 4 days delivery of biologically active
Ingredient or active ingredient.The bioactive ingredients or active ingredient refer to inhibition, zoogenetic infection or sense are mitigated or eliminated
Contaminate the substance of symptom.
The active pharmaceutical ingredient be selected from azithromycin, azithromycin hydrate, azithromycin pharmaceutically acceptable salt,
It isomers, other substances that can be changed into azithromycin and can release in animal body in the substance of azithromycin extremely
Few one kind.In some embodiments, the active pharmaceutical ingredient is azithromycin, azithromycin hydrate, azithromycin medicine
Acceptable salt and other at least one of substances that can release azithromycin in animal body on.In some realities
Apply in mode, the active pharmaceutical ingredient be azithromycin, azithromycin hydrate and its pharmaceutically acceptable salt in extremely
Few one kind.In some embodiments, the active pharmaceutical ingredient is azithromycin, azithromycin hydrate, or combinations thereof.?
In some embodiments, the active pharmaceutical ingredient is two water azithromycins.In some embodiments, the active medicine at
It is divided into azithromycin.In some embodiments, the active pharmaceutical ingredient is a water azithromycin.In some embodiments
In, the active pharmaceutical ingredient is 1.5 water azithromycins.
On the one hand, azithromycin injection for animals provided by the invention, can be solution type injection agent.
The solution type injection agent includes active pharmaceutical ingredient and solvent for injection, wherein active pharmaceutical ingredient defines such as
Preceding described, the solvent for injection is diethylene glycol monoethyl ether (such as Transcutol V).In some embodiments, described molten
Liquid type injection further includes the common additives of the injections such as PH conditioning agents.
The solution type injection agent, wherein calculated according to the volume of injection, with azithromycin, active pharmaceutical ingredient
A concentration of 50mg/mL-280mg/mL.A concentration of 50mg/mL-175mg/mL of the active pharmaceutical ingredient in some embodiments.
If concentration is too low, the total volume of injection is excessive when being administered, and compliance reduces, if excessive concentration, is unfavorable for drug safety
Property.
The solution type injection agent, administering mode can be hypodermic injection, intracutaneous injection, intramuscular injection, intravenous injection
Deng.In some embodiments, administering mode is administered intramuscular.
In some embodiments, the azithromycin injection for animals is solution type injection agent, by active pharmaceutical ingredient
It is formed with solvent for injection diethylene glycol monoethyl ether.
Previous solu type injection, preparation method may comprise steps of：The active pharmaceutical ingredient of recipe quantity is molten
In diethylene glycol monoethyl ether, stirring and dissolving；Lid is rolled in packing, tamponade, packs.
On the other hand, azithromycin injection for animals provided by the invention, can be freeze dried injection.
The freeze dried injection includes active pharmaceutical ingredient and NaTDC, wherein active pharmaceutical ingredient is as defined above
It is described.
The grain size of the active pharmaceutical ingredient of the freeze dried injection has the property that：Its D50 is 1 μm -10 μm, D90 3
μm-15μm.In some embodiments, the grain size of the active pharmaceutical ingredient of the freeze-dried powder has the property that：Its D50 is 4 μ
M-6 μm, D90 is 9 μm -12 μm.Active pharmaceutical ingredient grain size is excessive to be unfavorable for the dissolving of drug and stabilization after redissolving.
The freeze dried injection, which can be free of, solvent, can also contain a small amount of solvent such as water or diethylene glycol monoethyl ether.
In some embodiments, the freeze dried injection can contain 5% solvent no more than injection total weight.In some realities
It applies in mode, the freeze dried injection can contain 2% solvent no more than injection total weight, or be injected containing being no more than
1% solvent of agent total weight, or contain 0.5% solvent no more than injection total weight.
Aforementioned freeze dried injection, preparation method may comprise steps of：By active pharmaceutical ingredient and NaTDC
It is added in water for injection, using ball mill grinding 5min-30min, salt acid for adjusting pH value to 8.55 obtains mixture, by gained
Mixture is lyophilized using vacuum freeze drier, obtains freeze dried injection.
In some embodiments, the freeze dried injection, preparation method includes the following steps：By active pharmaceutical ingredient
It is added in water for injection with NaTDC, using ball mill grinding 15min, salt acid for adjusting pH value to 8.55 obtains mixture,
Gained mixture is lyophilized using vacuum freeze drier, obtains freeze dried injection.
The freeze dried injection is facing the used time, needs to be redissolved using diethylene glycol monoethyl ether, then could carry out
Administration.
The freeze dried injection, application method include the following steps：Face the used time, the freeze dried injection uses injection
Diethylene glycol monoethyl ether is redissolved, and solution type injection agent is obtained.The freeze dried injection, after redissolution, according to acquired solution
The volume of type injection calculates, with azithromycin, a concentration of 50mg/mL- of active pharmaceutical ingredient in acquired solution type injection
350mg/mL.In some embodiments, it is calculated according to the volume of acquired solution type injection, with azithromycin, acquired solution
A concentration of 50mg/mL-280mg/mL of active pharmaceutical ingredient in type injection.In some embodiments, it is noted according to acquired solution type
The volume for penetrating agent calculates, with azithromycin, a concentration of 50mg/mL- of active pharmaceutical ingredient in acquired solution type injection
175mg/mL.If concentration is too low, the total volume of injection is excessive when being administered, and compliance reduces, if excessive concentration, is unfavorable for
Drug safety.
The freeze dried injection, administering mode can be hypodermic injection, intracutaneous injection, intramuscular injection, intravenous injection etc..
In some embodiments, administering mode is administered intramuscular.
On the other hand, the present invention also provides irritating caused by a kind of reduction animal administration of azithromycin injection
Method：Azithromycin injection for animals above-mentioned is applied to animal.
The azithromycin injection can be solution type injection agent；The solution type injection agent includes active pharmaceutical ingredient
With solvent for injection；Wherein, active pharmaceutical ingredient is defined as described above, and the solvent for injection is diethylene glycol monoethyl ether
(such as Transcutol V)；The solution type injection agent, wherein calculated according to the volume of injection, with azithromycin, activity
A concentration of 50mg/mL-175mg/mL of drug ingedient；In some embodiments, the solution type injection agent further includes PH conditioning agents
The common additives of equal injections.
Azithromycin injection for animals provided by the invention, with azithromycin, according to the weight of administration object, activity at
Dividing can be according at least 5mg/kg drug administration by injection.In some embodiments, azithromycin injection for animals provided by the invention, with
Azithromycin, according to the weight of administration object, active constituent can according at least 7mg/kg drug administration by injection, after drug administration by injection,
Can in -12 days 3 days delivery of biologically active ingredient or biological effective components.In some embodiments, provided by the invention
Azithromycin injection for animals, with azithromycin, according to the weight of administration object, active constituent can be noted according at least 8mg/kg
Penetrate administration, after drug administration by injection, can in -12 days 3 days delivery of biologically active ingredient or biological effective components.In some implementations
In mode, azithromycin injection for animals provided by the invention, with azithromycin, according to the weight of administration object, activity at
Point after drug administration by injection, delivery of biologically active ingredient or biology can have in -12 days 3 days according to 10mg/kg drug administration by injection
Imitate ingredient.In some embodiments, azithromycin injection for animals provided by the invention, with azithromycin, according to administration
The weight of object, active constituent after drug administration by injection, can discharge life according to 20mg/kg drug administration by injection in -12 days 3 days
Object active constituent or biological effective components.In some embodiments, azithromycin injection for animals provided by the invention, with Ah
Miramycin meter, according to the weight of administration object, active constituent can according to 5mg/kg-20mg/kg drug administration by injection, after drug administration by injection,
It can in -12 days 3 days delivery of biologically active ingredient or biological effective components.
The present invention compared with the existing technology, it is advantageous that：
1) present invention provides a kind of azithromycin injection for animals, and irritation is relatively low, and life can be discharged in -14 days 1 day
Object active constituent or active ingredient, long action time, it is possible to reduce administration number of times can increase using compliance；
2) the injection component in the present invention is simple, can contain only active drug ingedient and solvent, thus preparation method
Simply, it is suitable for producing in enormous quantities；
3) injection in the prior art is mostly suspension, emulsion, Polymer Solution agent, microball preparation, injection implant
Or the unstable dosage form such as glue, or need in advance be chemically modified active pharmaceutical ingredient, difficulty soluble salt, prodrug is made
Deng the present invention can not modify azithromycin, be directly dissolved in Transcutol V and be made solution, stablize easily storage
It deposits；
4) compared to azithromycin aqueous solution injection, the azithromycin injection in the present invention can largely reduce dynamic
Object applies caused irritation, to significantly reduce pain and oedema situation.
Specific implementation mode
In order to make those skilled in the art more fully understand technical scheme of the present invention, it is non-that some are disclosed further below
Limiting embodiment, the present invention is described in further detail.
Reagent used in the present invention can be bought or can described method system through the invention from the market
It is standby and obtain.The source diethylene glycol monoethyl ether (Transcutol V) is good method lion, and " V " is model, represents for animals.
In the present invention, kg：Kilogram；g：Gram；mg：Milligram；ng：Nanogram；mL：Milliliter；min：Minute；h：Hour；q.s.：It is fixed
Hold；PEG：Polyethylene glycol；AUC：Area under the drug-time curve；Cmax：Up to Cmax；Tmax：Peak time；MIC：It is minimum antibacterial dense
Degree；SD：Standard deviation；CV：The coefficient of variation；AUCinf：Medicine when situation show that theoretically blood concentration drops to 0 is removed according to drug
When area under the curve, be calculated by corresponding software.
Freeze drying process of the present invention and condition：First stage, -40 DEG C of set temperature, setting time 30min, duration
180min；Second stage, -50 DEG C of set temperature, setting time 2min, duration 60min；Primary drying condition：Setting temperature
- 10 DEG C, setting time 60min, duration 2220min of degree, control vacuum 0.130MPa；Parsing-desiccation condition：Set temperature
30 DEG C, setting time 35min, duration 400min, control vacuum 0.000MPa.
Granulometry instrument of the present invention is Malvern laser granulometry 3000, and method is wet method.Specific droplet measurement
Method and parameter：Decentralized medium is purified water, particle refractive index 1.520, minute 10s, BACKGROUND Time 12s, obscurity
15%-20%, rotating speed 2500rpm.
The preparation of 1 azithromycin injection suspension of comparative example
Azithromycin injection suspension is prepared, prescription is as follows：
Preparation method：Two water azithromycins and NaTDC are added in water for injection, using ball mill grinding 15min,
Salt acid for adjusting pH value is drawn suspension for injection, is lyophilized using vacuum freeze drier, obtains freeze-dried powder to 8.55.Freeze
Dry powder is redissolved using a certain amount of 5% glucose, obtains injection suspension.
Detection gained suspension, the grain size for measuring the active constituent in suspension is that D50 is 5.77 μm, and D90 is 11.9 μm；
Suspension appearance uniform, mobility is preferable, and sedimentation is slow, and weight good dispersion, liquid does not glue wall, and syringeability is good, suitable injection.It will freeze
After dry powder is redissolved with 5% glucose solution, disperse Quick uniform, character is consistent with the suspension before freeze-drying.
The preparation of 2 azithromycin injection suspension of comparative example
Azithromycin injection suspension, prescription are as follows：
Preparation method：Two water azithromycins and NaTDC are added in water for injection, using ball mill grinding 15min,
Salt acid for adjusting pH value is drawn suspension for injection, is lyophilized using vacuum freeze drier, obtains freeze-dried powder to 8.55.Freeze
Dry powder uses a certain amount of PEG200:5% glucose (4:6) it redissolves, obtains injection suspension.
Detection gained suspension, the grain size for measuring the active constituent in suspension is that D50 is 4.51 μm, and D90 is 9.14 μm；
Suspension appearance uniform, mobility is preferable, and sedimentation is slow, and weight good dispersion, liquid does not glue wall, and syringeability is good, suitable injection.It will freeze
Dry powder PEG200:5% glucose (4:6) after redissolving, disperse Quick uniform, character is consistent with the suspension before freeze-drying.
The preparation of 3 azithromycin injection solution of embodiment
Azithromycin injection solution, prescription are as follows：
Preparation method：Two water azithromycins and NaTDC are added in water for injection, using ball mill grinding 15min,
Salt acid for adjusting pH value is drawn suspension for injection, is lyophilized using vacuum freeze drier, obtains freeze-dried powder to 8.55.Freeze
Dry powder is redissolved using a certain amount of Transcutol V, obtains injection solution.
The preparation of 4 azithromycin injection solution of embodiment
Azithromycin injects solution, and prescription is as follows：
Preparation method：Two water azithromycins of recipe quantity are dissolved in Transcutol V, stirring and dissolving；Packing, tamponade,
Lid is rolled, is packed.
The preparation of 5 azithromycin injection solution of embodiment
Azithromycin injects solution, and prescription is as follows：
Preparation method：With reference to embodiment 4.
Pharmacokinetic is tested in 6 dog of embodiment
Experimental method：Beasle dog (Beagle dog) is taken, according to the medication and dosage in the following table 1, using not
Same sample is administered beasle dog.Second is added to beasle dog forelimb medial head venous blood collection in different time sections after administration
Ethylenediamine tetraacetic acid (EDTA) dipotassium anti-coagulants, 12000rpm, 4 DEG C of centrifugation 2min, it is dense that LC/MS/MS (liquid chromatography mass spectrometric combination) method detects blood medicine
Degree calculates pharmacokinetic parameters according to the surveyed plasma concentration non-compartment model method of 6.3 softwares of WinNonlin.
Pharmacokinetic experimental method in 1 dog of table
Pharmaceutical solutions sample preparation method：
No. 1 sample：A concentration of 1.0mg/mL of azithromycin, a concentration of 0.2mg/mL of Citric Acid Mono；According to concentration,
The Citric Acid Mono and a water azithromycin for weighing recipe quantity are dissolved in a certain amount of water for injection, stirring and dissolving, and ultrasonic 2min is
?.
No. 2 samples：A concentration of 366.8mg/mL of azithromycin, a concentration of 74mg/mL of citric acid；According to concentration, claim
The Citric Acid Mono and two water azithromycins for taking recipe quantity are dissolved in a certain amount of water for injection, and stirring and dissolving to obtain the final product.
No. 3 samples：According to the prescription and preparation method of embodiment 4, solution is obtained.
Experimental result：Each data are referring to table 2.
Pharmacokinetic experimental result in 2 dog of table
Sample 1, Tmax 0.417h, Cmax 731ng/mL, AUCINF 6240ng/mL；Wherein 0.25h is a concentration of
520ng/mL, blood concentration is 82.6ng/mL for 24 hours.
Sample 2, Tmax 0.25h, Cmax 6181.3ng/mL, AUCINF 28564.3ng/mL；Wherein, 72h blood medicine
A concentration of 91ng/mL, 96h blood concentration are 48ng/mL, and 168h blood concentrations are 30.2ng/mL.
Sample 3, Tmax 1.0h, Cmax 859.6ng/mL, AUCINF 33647.1ng/mL；Wherein, 72h blood medicine is dense
Degree is 192ng/mL, and 96h blood concentrations are 124ng/mL, and 168h blood concentrations are 43.2ng/mL.
Rapid (the release of 0.25h, that is, reachable it is found that pharmaceutical solutions provided by the invention (No. 3 samples) work according to result
To 695ng/mL), 96h blood concentrations are 124ng/mL, and (sample 1) blood concentration 82.6ng/ for 24 hours was administered orally far above single day
ML, i.e., the blood concentration after 4 days are still far above single oral blood concentration for 24 hours；Also oral 48h blood concentrations are apparently higher than
34.8ng/mL, this concentration remain above part bacterium MIC value (minimum inhibitory concentration, streptococcus pneumonia, gonorrhoea how Roche bacterium etc.,
Referring to the following table 3, come from Agricultural University Of Nanjing, 2011, Wu Kangnian, master thesis：The clinical peace of azithromycin capsule
Full property experiment and the pharmacokinetic to dog).Therefore No. 3 samples of solution injection compare oral preparation, can rapid-onset
And the effect of playing long-acting, maintaining at least 4 days.Cmax reaches 6181.3ng/ after aqueous solution injection (No. 2 samples) administration
ML, blood medicine is dense after being far above using Transcutol V as solution injection (No. 3 samples) Cmax 859.6ng/mL, 96h of solvent
48ng/mL is spent, is far below using Transcutol V as solution injection (No. 3 samples) 96h blood concentration 124ng/mL of solvent,
Therefore, the aqueous solution injection for comparing comparable sodium, using Transcutol V as the solution injection of solvent, plasma concentration curve
Gently, peak value is relatively low, is less prone to intoxicating phenomenon, AUC value higher, better efficacy under the same time.
If using 82.6ng/mL as effective Mlc, in the case where thinking AUC numerical value and dosage substantially linear correlation circumstance,
The injection that the present invention is calculated continues to reach for 3 days effective injection volume of effective Mlc 82.6ng/mL as 17.5mg/
Kg*82.6ng/mL/192ng/mL=7.53mg/kg continues the effective injection volume for reaching effective Mlc 82.6ng/mL for 1 day
For 17.5mg/kg*82.6ng/mL/273ng/mL=5.29mg/kg (* indicates multiplication sign).
The antimicrobial spectrum and antibacterial activity (MIC mg/L) of 3 part macrolide antibiotics of table
| Bacterium | Erythromycin | Azithromycin | Clarithromycin | Roxithromycin | Dirithromycin |
| Streptococcus pneumonia | 0.015-0.25 | 0.015-0.25 | 0.015-0.06 | 0.03-0.12 | 0.16-0.12 |
| Streptococcus pyogenes | 0.03-4.0 | 0.015-0.25 | 0.05-4.25 | 0.06-2.0 | 0.12-2.0 |
| Monocyte Li Site bacterium | 0.5-4.0 | 2.0-4.0 | 0.25-2.0 | 1.0-2.0 | 0.12-2.0 |
| Bacillus perfringens | 1.0 | 0.25-0.5 | 0.5 | 2.0 | 4.0 |
| Branhamella catarrhalis | 0.25 | 0.06 | 0.12-0.25 | 0.5-1.0 | 0.25 |
| Gonorrhoea how Roche bacterium | 0.25-0.5 | 0.03-0.06 | 0.25-0.5 | 0.2-1.0 | 2.0-4.0 |
| Bordetella pertussis | 0.03 | 0.06 | 0.03 | 0.25 | 0.5 |
| Campylobacter jejuni | 1.0 | 0.12 | 2.0 | 4.0 | 0.25 |
| Helicobacter pylori | 0.25 | 0.25 | 0.03 | 0.25 | 0.5 |
| Haemophilus influenzae | 2.0-8.0 | 0.25-1.0 | 2.0-9.0 | 4.0-16.0 | 8.0->16 |
| Legionella pneumophilia | 2.0 | 2.0 | 0.25 | 0.5 | 16 |
| Bacteroides fragilis | 4.0-8.0 | 2.0-4.0 | 2.0-8.0 | 32 | >128 |
| Chlamydia trachomatis | 2.0 | 0.25 | 0.12 | 1.0 | 4.0 |
Embodiment 7 investigates irritation of the drug to animal
According to the following table 4, muscle note is carried out to beasle dog (Beagle dog) with identical dosage using different samples
Penetrate administration, 3/group, observation 1h, 6h, dog for 24 hours, after 72h, 168h injection site edema situation, evaluation drug is to lead for animal
The irritation come.Eye concern is penetrated after animal subject reacts (struggle, scream etc.) and injection when irritation evaluation index includes injection
Position oedema situation, correlated judgment standard are as follows：
Animal subject reacts：Struggle situation is divided into serious (3 grades), moderate (2 grades), slight (1 grade), nothing (0 grade) four journeys
Degree, such as following table：
4 animal subject of table reacts hierarchical table
Injection site edema situation：Oedema situation is divided into serious (3 grades), moderate (2 grades), slight (1 according to oedema radius
Grade), without (0 grade) four degree, table specific as follows：
5 animal subject oedema situation hierarchical table of table
The preparation method of formulation samples：
No. 3 samples：According to the prescription and preparation method of embodiment 4, solution is obtained.
No. 4 samples：According to the prescription and preparation method of comparative example 1, suspension is obtained.
No. 5 samples：According to the prescription and preparation method of comparative example 2, suspension is obtained.
No. 6 samples：Diethylene glycol monoethyl ether (Transcutol V).
No. 7 samples：5% glucose solution.
In experiment, each group administrations are as shown in the table：
Irritation research experiment method of 6 drug of table to animal
Remarks：A-c subscripts indicate solution (sample 3), suspension (sample 4 and sample 5) sample drug administration information：Sample is dense
Degree is 175mg/ml, and administered volume 0.1ml/kg, i.e. dosage are 17.5mg/kg.
Irritant experiment result：Referring to table 7
Irritation research experiment result of 7 drug of table to animal
Remarks：With reference to aforementioned grade scale, this experimental animal quantity n=3, classification results are that each group every is classified
Average ± standard deviation afterwards, i.e. Mean ± SD.
According to experimental result it is found that compared to same concentration Azithromycin mix suspension liquid (No. 4 samples and No. 5 samples), with two
Ethylene glycol monomethyl ether is the pain level and note of beasle dog after the solution injection (No. 3 samples) of solvent is applied to beasle dog
It is considerably lower to penetrate position oedema rank, it is seen that can largely delay by the solution injection of solvent of diethylene glycol monoethyl ether
Solve the stimulation phenomenon of animal administration of azithromycin.
The method of the present invention is described by preferred embodiment, related personnel can obviously hold within the present invention,
Method described herein and application are modified or are suitably changed and combined in spirit and scope, to realize and apply the present invention
Technology.Those skilled in the art can use for reference present disclosure, be suitably modified technological parameter realization.In particular, it should be pointed out that institute
There are similar replacement and change apparent to those skilled in the art, they are considered as being included in the present invention
It is interior.
Claims (10)
1. a kind of azithromycin solution type injection agent for animals, including active pharmaceutical ingredient and solvent for injection；Wherein, the activity
Drug ingedient be selected from azithromycin, azithromycin hydrate, azithromycin pharmaceutically acceptable salt, isomers, it is other can
It is changed into the substance of azithromycin and at least one of substance of azithromycin can be released in animal body, feature exists
In the solvent for injection is diethylene glycol monoethyl ether.
2. a kind of lyophilized azithromycin injection for animals, which is characterized in that it includes active pharmaceutical ingredient and NaTDC,
Face the used time need to be carried out with diethylene glycol monoethyl ether redissolve be configured to injection, then can just be administered, wherein the activity
Drug ingedient be selected from azithromycin, azithromycin hydrate, azithromycin pharmaceutically acceptable salt, isomers, it is other can
It is changed into the substance of azithromycin and at least one of substance of azithromycin can be released in animal body.
3. injection according to claim 1, calculated according to the volume of injection, with azithromycin, active medicine at
A concentration of 50mg/mL-280mg/mL divided.
4. injection according to claim 2, which is characterized in that active pharmaceutical ingredient is a concentration of in the injection
50mg/mL-350mg/mL。
5. injection according to claim 2, which is characterized in that the grain size of the active pharmaceutical ingredient has following special
Property：Its D50 is 1 μm -10 μm, and D90 is 3 μm -15 μm.
6. injection according to claim 1 or 2, with azithromycin, according to the weight of administration object, active medicine at
Divide according at least 5mg/kg drug administration by injection.
7. injection according to claim 1 or 2, which is characterized in that the injection after injection can be at 1 day -14
Delivery of biologically active ingredient or active ingredient in it.
8. injection according to claim 1 or 2 passes through administered intramuscular.
9. a kind of method preparing injection described in claim 1, including：(a) active material of recipe quantity is dissolved in diethyl
In glycol list ethylether, stirring and dissolving；(b) it dispenses, lid is rolled in tamponade, packs.
10. a kind of method preparing the injection described in claim 2, including：Active pharmaceutical ingredient and NaTDC are added
Enter in water for injection, using ball mill grinding 5min-30min, salt acid for adjusting pH value to 8.55 obtains mixture, then by institute
It obtains mixture to be lyophilized using vacuum freeze drier, obtains lyophilized azithromycin injection.
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| CN201710259049 | 2017-04-20 | ||
| CN2017102590492 | 2017-04-20 |
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| CN201810347546.2A Pending CN108721209A (en) | 2017-04-20 | 2018-04-18 | A kind of azithromycin injection for animals |
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| PB01 | Publication | ||
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| TA01 | Transfer of patent application right | ||
| TA01 | Transfer of patent application right |
Effective date of registration: 20190527 Address after: Room 201, No. 1 Industrial North Road, Songshan Lake High-tech Industrial Development Zone, Dongguan City, Guangdong Province Applicant after: Dongguan Dongguan Sunshine Animal Health Pharmaceutical Co.,Ltd. Address before: 523808 No. 1 Industrial North Road, Hubei Industrial Park, Songshan, Dongguan, Guangdong Applicant before: SUNSHINE LAKE PHARMA Co.,Ltd. |
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Application publication date: 20181102 |