CN108670951A - A kind of compound sustained-released injection of gentamicin sulphate-Lincomycin Hydrochloride for animals and preparation method thereof - Google Patents
A kind of compound sustained-released injection of gentamicin sulphate-Lincomycin Hydrochloride for animals and preparation method thereof Download PDFInfo
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Abstract
The invention belongs to veterinary drug technical field, a kind of compound sustained-released injection of gentamicin sulphate Lincomycin Hydrochloride for animals and preparation method thereof is disclosed.It is composed of the following components per 100g injections：0.1 ~ 30g of gentamicin sulphate, 0.1 ~ 20g of Lincomycin Hydrochloride, 0.01 ~ 5g of slow-released carrier, 0 ~ 20g of stabilizer, 0 ~ 3g of analgesic, 20 ~ 30g of organic solvent, surplus are water for injection.Stabilizer is added in partial syringe water, stirring and dissolving；Two kinds of main ingredient gentamicin sulphates and Lincomycin Hydrochloride are then added in system, stirring and dissolving to clear obtains system A；Slow-released carrier is added in system A, stirring obtains system B to being completely dissolved；Analgesic is dissolved in organic solvent, system C is obtained；After system C and system B mixings, water for injection is settled to 100g to get the compound sustained-released injection of gentamicin sulphate Lincomycin Hydrochloride for animals.The compound sustained-released injection of gentamicin sulphate Lincomycin Hydrochloride for animals prepared by the present invention has slow-release function.
Description
Technical field
The invention belongs to veterinary drug technical fields, and in particular to a kind of gentamicin sulphate for animals-Lincomycin Hydrochloride compound
Slow-release injection and preparation method thereof.
Background technology
Porcine respiratory disease is a kind of general name of multifactor caused breathing problem, by primary cause of disease and secondary venereal disease
Original mixing causes.Currently, in pig farm, the single cause of disease case of infection is really caused only to account for 9%, and 91% porcine respiratory disease
Case is all by more than two cause of diseases caused mixed infections, with reproductive and respiratory syndrome virus, circovirus, haemophilus parasuis, hammer
The compound infection rate highest of bacterium, and the secondary infection caused by Streptococcus suis, haemophilus parasuis etc., lethality is high, harm
Seriously, individual primary infection, lethality is not high, and relative hazard is little, such as：Pig is panted caused by porcine mycoplasmal infects
Disease will not cause the death of pig, but belong to chronic wasting disease, cause the feed conversion rate of pig to reduce, growth performance is poor；Again
Such as:After 7 type Streptococcus suis of pig secondary infection, the pathogenicity of reproductive and respiratory syndrome virus can be enhanced, the sick pig state of an illness is caused further to deteriorate,
It is final to keep sick pig dead；The case fatality rate that pig individually infects circovirus morbidity is relatively low, but is caused after secondary infection haemophilus parasuis
Dead rate is up to 80% or more.So the top priority of prevention porcine respiratory disease is solved by gram-positive bacteria Streptococcus suis, leather
Secondary infection problem caused by Lan Shi negative bacterium haemophilus parasuis.
Currently, generally add the method for symptomatic treatment using vaccine prevention, antibacterials for the prevention of porcine respiratory disease,
Such as：Antibacterials add drug for abating fever, antibacterials to add class drug etc. of relievining asthma.However this therapy be it is palliative,
No specific aim is treated, cannot effectively inhibit or kill to mix caused by gram-positive bacteria, Gram-negative bacteria and porcine mycoplasmal
Close infection.Although the reason of for morbidity, also someone inhibits using different antibacterials or kills gram-positive bacteria pig hammer
Bacterium, Gram-negative bacteria haemophilus parasuis and porcine mycoplasmal, such as：Original net medicine, Florfenicol, tylosin, astragalus polyose
Etc. use in conjunction, however the use in conjunction of this folk prescription-folk prescription drug there are the compatibilities between drug whether rationally and poison is secondary makees
The problems such as using.
Lincomycin may act on the ribosomes 50S subunits of pathogen, the extension of peptide chain be prevented, to inhibit bacterial cell
Protein synthesis, not only have a stronger killing effect to primary cause of disease-mycoplasma, but also blue to the leather in secondary cause of disease
Family name's positive bacteria, as Streptococcus suis also has stronger killing effect, meanwhile, gentamicin, can be with as aminoglycoside antibiotics
Bacterial ribosome 30S subunits combine, inhibit the synthesis of bacterio protein, and cause indirectly bacterial cell membrane, cell wall lack
Damage has stronger killing effect to the Gram-negative bacteria in secondary cause of disease, such as haemophilus parasuis.
Invention content
The purpose of the present invention is to provide a kind of compound sustained-released injection of gentamicin sulphate-Lincomycin Hydrochloride for animals and
Preparation method.
To achieve the above object, the technical solution adopted by the present invention is as follows：
A kind of compound sustained-released injection of gentamicin sulphate-Lincomycin Hydrochloride for animals, per 100g injections by following components group
At：
0.1 ~ 30g of gentamicin sulphate, 0.1 ~ 20g of Lincomycin Hydrochloride, 0.01 ~ 5g of slow-released carrier, 0 ~ 20g of stabilizer, analgesic
0 ~ 3g of agent, 20 ~ 30g of organic solvent, surplus are water for injection；
Wherein, the slow-released carrier is one kind in sodium carboxymethylcellulose, hydroxypropyl methyl cellulose, gelatin, Arabic gum
Or two or more combination；The organic solvent is the group of one or more of 1,2- propylene glycol, glycerine, absolute ethyl alcohol
It closes.
Preferably, the slow-released carrier is the combination of cellulose family carrier and glue class two kinds of carriers of carrier, and cellulose family
The quality proportioning of carrier and glue class carrier is 2: 1；Wherein, cellulose family carrier is sodium carboxymethylcellulose and/or hydroxypropyl first
Base cellulose, glue class carrier are gelatin and/Arabic gum.
Preferably, the stabilizer is one or both of polyethylene glycol 200, polyethylene glycol 400, Macrogol 600
Above combination.
Preferably, the analgesic is benzyl alcohol.
Preparation method includes the following steps：
（1）Stabilizer is added in partial syringe water, stirring and dissolving；It is big mould that two kinds of main ingredient sulfuric acid celebratings are then added in system
Element and Lincomycin Hydrochloride, stirring and dissolving to clear obtain system A；
（2）Slow-released carrier is added in system A, stirring obtains system B to being completely dissolved；
（3）Analgesic is dissolved in organic solvent, system C is obtained；
（4）After system C and system B mixings, water for injection is settled to 100g can to get gentamicin sulphate for animals-hydrochloric acid woods
The compound sustained-released injection of mycin.
The compound sustained-released injection of gentamicin sulphate-Lincomycin Hydrochloride for animals prepared by the present invention has slow-release function,
The present invention is made drug dissolving in the carrier, is formed matrix type tiny spherical solid, delay drug in body by micro-encapsulation technology
The speed of interior release extends action time, reduces Animal stress, increases compliance.And because having slow releasing function, drug to release
Slow down, the Nephrotoxicity of the gentamicin caused by dosage is excessive can be reduced.Two kinds of Drug combinations, for gram
Porcine respiratory disease has good therapeutic effect caused by positive bacteria and negative bacterium, has a vast market foreground.
Specific implementation mode
Below in conjunction with specific embodiment, the present invention will be further described.It should be understood that following embodiment is merely to illustrate this
The range of invention and is not intended to limit the present invention.
Embodiment 1-10
A kind of compound sustained-released injection of gentamicin sulphate-Lincomycin Hydrochloride for animals is shown in Table 1 per the prescription of 100g injections.
Comparative example 1-3
The preparation method of embodiment 1-10 and comparative example 1-3 products, include the following steps：
（1）, by stabilizer be added partial syringe water in, stirring and dissolving；It is big that two kinds of main ingredient sulfuric acid celebratings are then added in system
Mycin and Lincomycin Hydrochloride, stirring and dissolving to clear obtain system A；
（2）, slow-released carrier is added in system A, stirring obtains system B to being completely dissolved（When slow-released carrier additive amount is 0,
Omit this step）；
（3）, analgesic is dissolved in organic solvent, obtain system C；
（4）, by system C and system B（It is herein system A when slow-released carrier additive amount is 0）After mixing, water for injection constant volume
To 100g to get corresponding product.
Visual inspection
The appearance of the compound sustained-released injection of gentamicin sulphate-Lincomycin Hydrochloride for animals obtained by embodiment 1-10 be it is yellowish extremely
The clear liquid of yellowish green.
Stability test
The Example 1-10 gained compound sustained-released injection of gentamicin sulphate-Lincomycin Hydrochloride for animals is respectively into steady when passing through
Qualitative test, accelerated stability test, anti-freezing stability test observe the stability of injection of the present invention, are confirmed whether have
The wild effects such as discoloration, precipitation occur.
1, test of time
Injection is stored 6 months under the conditions of room temperature natural trend obtained by Example 1-10, observation indicate that：Embodiment 1-
10 gained injection appearances are as before, and no situations such as changing colour, being precipitated, content reinspection is qualified, illustrates that ageing stability is good.
2, accelerated test
Injection obtained by embodiment 1-10 is sub-packed in polyester bottles, sealing be placed on 40 DEG C of temperature, relative humidity 70% adds
90d is stored in fast case, samples and observes every 30d, and content is rechecked.The result shows that：Injection is in warm obtained by embodiment 1-10
At all time points after storage, appearance is as before, and without discoloration, be precipitated situations such as, illustrate that heat storage stability is good.
3, anti-freezing stability
Injection obtained by embodiment 1-10 is preserved after a week for -20 DEG C in refrigerator, restores to room temperature to observe.The result shows that：It is real
It is as before to apply injection appearance obtained by a 1-10, no situations such as changing colour, being precipitated, content reinspection is qualified, shows that freezing-resistance is good
It is good.
Combination susceptibility testing
It is carried out with the second line of a couplet using the 1 gained compound sustained-released injection of gentamicin sulphate-Lincomycin Hydrochloride for animals of embodiment as sample
Close drug sensitive test.
First, 29 plants of pig hammers of Lincomycin Hydrochloride and gentamicin sulphate pair are measured using micro broth dilution method respectively
Bacterium（It is provided by Harbin veterinary institute）Separation strains, 16 plants of haemophilus parasuis（It is provided by Harbin veterinary institute）Separation
The minimal inhibitory concentration of strain（MIC）.Then, 29 plants of Streptococcus suis are detached after measuring the combination of two medicines using Checkerboard microdilution method
Strain, 16 plants of haemophilus parasuis separation strains antibacterial effect, inquire into Lincomycin Hydrochloride and gentamicin sulphate to Streptococcus suis,
The in vitro antibacterial activity of haemophilus parasuis.
1, minimal inhibitory concentration（MIC）It measures
Using micro broth dilution method, measure respectively 29 plants of Streptococcus suis of Lincomycin Hydrochloride and gentamicin sulphate pair, 16 plants
The MIC value of haemophilus parasuis.
（1）, Streptococcus suis separation strains are inoculated in containing 5%（Percentage by volume）The brain heart infusion agar culture medium of cow's serum
In, haemophilus parasuis is inoculated in containing 0.1%（Quality percentage by volume, g: ml）In the trypticase soy broth of NAD,
37 DEG C of overnight incubations；Adjust 0.5 maxwell unit i.e. 1.5 × 10 of bacterium solution turbidity8CFU/mL, then by bacterium solution sterile saline
Make 1: 1000 volume to dilute again.
（2）, take sterile 96 hole microwell plate, above-mentioned Streptococcus suis or haemophilus parasuis dilution is added, except the 1st hole adds
Outside 180 μ L, the 2nd ~ 24 hole adds 100 μ L；It is followed in the 1st hole and 20 μ L of antibiotic stoste is added, 100 μ L are sucked out after being sufficiently mixed and add
Enter in the 2nd hole, with the doubling dilution of genealogy of law row to the 23rd hole, 100 μ L is sucked out after being sufficiently mixed and abandon；24th hole is free of antibiotic,
For positive for bacteria control wells.Covered after mixing, in 37 DEG C be incubated 18 ~ for 24 hours.
The antibiotic stoste that 1st hole is added is the aqueous solution for the corresponding single drug to be determined prepared with water for injection,
A concentration of Lincomycin Hydrochloride stoste：40000 μ g/mL, gentamicin sulphate stoste：4000µg/mL.
（3）, to visually observe, Streptococcus suis and haemophilus parasuis group drug Cmin hole are without bacterial growth person（Carefully
Bacterium growth complete inhibition）, the MIC of as tested bacterium.Before the MIC for reading bacterial strain, the bacterium life of positive for bacteria control wells should be checked
Whether long situation is good.
Drug sensitivity tests are with reference to U.S. clinical laboratory standard（CLSI/ NCCLS, 2005）The catastrophe point of streptococcus intermedius
（Break point）Judged, minimal inhibitory concentration MIC value catastrophe point criterion：Lincomycin, it is sensitive（S）≤0.5µ
G/mL, intermediary（I）1-2 μ g/mL, drug resistance（R）≥4µg/mL；Gentamicin, it is sensitive（S）≤ 4 μ g/mL, intermediary（I） 8 μg/
ML, drug resistance（R）≥16 µg/mL.Gentamicin is to the FDA critical values of enterobacteriaceae：It is sensitive（S）≤ 4 μ g/mL, intermediary（I）
8 μ g/mL, drug resistance（R）≥16µg/mL.
2, Checkerboard microdilution method combines susceptibility
According to single medicine MIC value of the every plant of bacterium measured, the drug concentration of joint susceptibility is determined.Two medicines use bacterium dilution respectively（Together
Single medicine drug sensitive detection, bacterium solution turbidity about 1.5 × 105 CFU/mL）Carry out doubling dilution：2 MIC、MIC、1/2 MIC、1/4 MIC、
1/8 MIC respectively takes 50 μ L, and combined crosswise is in 96 hole microwell plates（Such as table 3）, make to be added in each row of microwell plate identical dense
The gentamicin sulphate of degree, Lincomycin Hydrochloride concentration are then followed successively by 2MIC, MIC, 1/2MIC, 1/4MIC, 1/8 MIC；Micro-
In every a line of orifice plate, Lincomycin Hydrochloride concentration is identical, and gentamicin sulphate concentration is followed successively by 2MIC, MIC, 1/2MIC, 1/
4MIC、1/8MIC.It is uniformly mixed and covers, be incubated for 24 hours in 37 DEG C.Bacterial growth index is the same as single medicine drug sensitive test, asepsis growth
Lowest concentration of drug be combination when MIC.
Mlc index is obtained by calculating（Fractional Inhibitory Concentration, FIC）, sentence
The interaction of disconnected drug combination.Criterion is：When the MIC of Lincomycin Hydrochloride when FIC=drug combinations/be used alone
Gentamicin sulphate MIC, FIC refer to when the MIC of gentamicin sulphate when Lincomycin Hydrochloride MIC+ use in conjunction/be used alone
Number≤0.5, for synergistic effect；0. 5 <FIC≤1 is summation action；1 <FIC≤2.0 are unrelated effect；FIC >2. 0,
For antagonism.
3, test result
Two prescriptions with and the test results of 29 plants of Streptococcus suis of use in conjunction pair be shown in Table 4-5, show：When Lincomycin Hydrochloride is applied alone
MIC50, MIC90 be respectively 8 μ g/mL and 256 μ g/mL, after combination be respectively 4 μ g/mL and 128 μ g/mL；Gentamicin sulphate
MIC50, MIC90 when being applied alone are respectively 16 μ g/mL and 128 μ g/mL, are respectively 4 μ g/mL and 64 μ g/mL after combination.Connection
With the rear FIC for removing 8 plants of Streptococcus suis>1, that is, combine and unrelated or antagonism is shown to this 8 plants of bacterium（Account for 27.58%）Outside, remaining bacterium
Strain MIC has different degrees of reduction, index≤1 FIC to share to remaining 21 plants of Streptococcus suis（Account for 72.42%）For
It is added or acts synergistically.
Two prescriptions with and the test results of 16 plants of haemophilus parasuis of use in conjunction pair be shown in Table 6-7, show：Hydrochloric acid woods can be mould
MIC50, MIC90 when element is applied alone are respectively 8 μ g/mL and 16 μ g/mL, are respectively 4 μ g/mL and 250 μ g/mL after combination；Sulfuric acid
MIC50, MIC90 when gentamicin is applied alone are respectively 0.8 μ g/mL and 4 μ g/mL, are respectively 0.4 μ g/mL and 50 μ g/ after combination
mL.The FIC of 1 haemophilus parasuis is removed after combination>1, that is, combine and unrelated or antagonism is shown to this 1 plant of bacterium（Account for 6.25%）
Outside, remaining bacterial strain MIC has different degrees of reduction, index≤1 FIC to share to remaining the 15 plants bloodthirsty bars of secondary pig
Bacterium（Account for 93.75%）To be added or acting synergistically.
Conclusion：It is thermophilic to 29 plants of Streptococcus suis separation strains, 16 plants of secondary pigs after the combination of both Lincomycin Hydrochloride and gentamicin sulphate
The MIC ratios of blood bacillus separation strains, which are applied alone, different degrees of reduction, wherein 72.42% Streptococcus suis separation strains and 93.75%
Haemophilus parasuis FIC≤1, show as be added or act synergistically.So to treatment Streptococcus suis, haemophilus parasuis sense
Dye, using Lincomycin Hydrochloride and gentamicin sulphate scheme of combination drug therapy, can be improved external antibacterial effect.
It is sample to gentamicin sulphate lincomycin hydrochloride injection made from other embodiment using this test method
Carry out the experiment of joint susceptibility.
As a result show：Product prepared by the prescription of gentamicin sulphate Lincomycin Hydrochloride different proportion, drug combination
External antibacterial effect can be improved afterwards.
Hemolytic is tested
Haemolysis is carried out using the 1 gained compound sustained-released injection of gentamicin sulphate-Lincomycin Hydrochloride for animals of embodiment as tested material
Property experiment.
Experimental animal：New Zealand White Rabbit, 2.8 ~ 3.0kg of weight are provided by Harbin Nangang District prosperity farm.
New fresh rabbit blood 10mL is taken, is set in conical flask, fibrinogen is removed, defibrinated blood is made, physiological saline is added
About 10 volumes are measured again, are shaken up, and 1000-1500r/min centrifuges 15min, remove supernatant, and the red blood cell of precipitation uses physiological saline again
It washs 2-3 times as stated above, until the not aobvious red of supernatant.Gained red blood cell is made into the red thin of 2wt% with physiological saline
Born of the same parents' suspension, is for experiment.
Clean tube 7 is taken, is numbered, No. 1-5 pipe is test sample pipe, and No. 6 pipes are negative control pipe, No. 7 Guan Weiyang
Property control tube after mixing, stand by red cell suspension, physiological saline or distilled water, the tested material for sequentially adding 2wt% shown in table 8
It sets in 37 DEG C ± 0.5 DEG C of insulating box and is incubated, start to observe 1 time every 15min, after 1h, observe 1 time, see every 1h
Examine 3h.
If the solution in experiment is in clear and bright red, tube bottom is acellular to be remained or has a small amount of red blood cell to remain, and shows there is haemolysis
Occur；If red blood cell all sinks, supernatant fluid achromatism and clarity shows that no haemolysis occurs；If there is brownish red or reddish brown in solution
Color flocculent deposit, does not disperse after shaking, shows there is red blood cell condensation.
All time points observe result：1 ~ No. 6 pipe upper solution is in water white transparency, and red blood cell sinks, and shows that no haemolysis is anti-
The red blood cell answered, and sunk disperses quickly through shaking, no brown or rufous flocculent deposit, shows that no Coagulation test occurs；7
Number positive control pipe has haemolysis generation.The result shows that：Gentamicin sulphate for animals-Lincomycin Hydrochloride compound prepared by the present invention
0.1 ~ 0.5mL of slow-release injection does not generate haemolysis and cohesion in 3h to rabbit erythrocyte.Therefore, according to result above
It can be determined that injection safety.
Skin irritation test
Skin is carried out using the 1 gained compound sustained-released injection of gentamicin sulphate-Lincomycin Hydrochloride for animals of embodiment as tested material
Irritation test.
Take 4 rabbit, half male and half female.Every animal sub-cage rearing；Before administration for 24 hours, animal vertebra both sides antimere
It loses hair or feathers, hair removal section area is 4cm × 6cm, and experiment is using androgynous left and right sides self-contrast；Left side hair removal section applies tested material
0.5mL/ times, right side hair removal section applies bare substrate（Physiological saline）0.5mL/ times, non-stimulated gauze and adhesive plaster is used in combination to be fixed,
For 24 hours remaining tested material is removed with warm water afterwards；1h after coating, for 24 hours, 48h, 72h, visually observe and record and smear position variation
Situation, such as whether there is or not erythema and oedema.According to skin wound repair standards of grading（Table 9）It scores, then presses skin thorn again
Swash intensity evaluation standard（Table 10）It is evaluated.
Test result：1h after drug withdrawal, for 24 hours, 48h, 72h, gentamicin sulphate-Lincomycin Hydrochloride for animals prepared by the present invention
Compound sustained-released injection is 0 to the average value of rabbit intact skin all time points reaction integral, by skin irritatin intensity evaluation
The compound sustained-released injection of gentamicin sulphate-Lincomycin Hydrochloride for animals prepared by the present invention known to standard is non-stimulated to skin.
Meanwhile pathologic examination as a result, result be discontinued after 1h, for 24 hours, 48h, 72h histological observation be showed no exception.
Sustained release preparation is compared with ordinary preparation effect
For the compound sustained-released injection of gentamicin sulphate-Lincomycin Hydrochloride for animals more of the invention prepared and both main ingredients
Difference on effect between the normal injection of composition carries out following comparative testing.
Experimental animal：Select the natural occurrence case of porcine respiratory disease.
Test drug：Embodiment 1, comparative example 1-3 products.
Experiment grouping：Natural occurrence case 180 is chosen, is randomly divided into 6 groups, every group 30, wherein five groups for the treatment of groups, one
Group control group, grouping situation are shown in Table 11.
Examine and record administration before, administration after and be discontinued after each group test pig occur clinical symptoms, include mainly：
Cough, respiratory rate, nasal secretion etc..The generation of each group test pig symptom is recorded simultaneously, is developed, is lapsed to and Disappearance Scenarios,
Finally it is assessed using quantitative target, specific principle such as table 12 of giving a mark.
Clinical efficacy judges：The effect of clinically by three death rate, effective percentage and cure rate index evaluation drugs；Have
Efficiency refers to that the quantity of the test pig of above-mentioned clinical symptoms partial disappearance accounts for the ratio of test pig sum；Cure rate refers to above-mentioned faces
The quantity for the test pig that bed symptom all disappears accounts for the ratio of test pig sum；The death rate refers to that the number of dead test pig occurs
Amount accounts for the ratio of test pig sum.The death toll of each group test pig and death time in detail after record administration, symptom, which improves, to be tested
The quantity of pig and the quantity of symptom extinction test pig, the final death rate, effective percentage and the cure rate for calculating each group test pig.
Test result：This experiment passes through the clinical efficacy of three death rate, effective percentage and cure rate metrics evaluation each groups, respectively
The concrete condition of group is as shown in table 13.
As shown in table 13：The control group death rate is not administered and is up to 60%, prodigious economic loss is caused to raiser；Continuously
Commonly group 1 is efficient compared with the common sustained release group organized 2 and be administered one day of three days compounds of successive administration for the compound of administration one day
It is relatively low with cure rate；And three days compounds of successive administration commonly group 2 compared with only one day sustained release group of administration, effective percentage with control
More rate otherness is not notable, compared with control group not being administered, significantly improves.Sustained release group 1 or 2 is compareed compared with compound commonly group 1,
Effect is slightly better than the latter, but because slow-released carrier proportioning changes, slow release effect can not show a candle to sustained release group.
The above test results show that the compound sustained-released injection of gentamicin sulphate-Lincomycin Hydrochloride for animals of the present invention
The effect that is administered once is equivalent to the effect of compound ordinary preparation successive administration three times, has obviously slow release effect.This is right
In clinical practice application, drug cost can be substantially reduced, mitigates Animal stress pain reaction, raiser's medication facilitates fast
It is prompt.Compound preparation of the present invention with slow releasing function treats porcine respiratory disease with extraordinary application prospect.
Claims (5)
1. a kind of compound sustained-released injection of gentamicin sulphate-Lincomycin Hydrochloride for animals, which is characterized in that per 100g injections
It is composed of the following components：
0.1 ~ 30g of gentamicin sulphate, 0.1 ~ 20g of Lincomycin Hydrochloride, 0.01 ~ 5g of slow-released carrier, 0 ~ 20g of stabilizer, analgesic
0 ~ 3g of agent, 20 ~ 30g of organic solvent, surplus are water for injection；
Wherein, the slow-released carrier is one kind in sodium carboxymethylcellulose, hydroxypropyl methyl cellulose, gelatin, Arabic gum
Or two or more combination；The organic solvent is the group of one or more of 1,2- propylene glycol, glycerine, absolute ethyl alcohol
It closes.
2. the compound sustained-released injection of gentamicin sulphate-Lincomycin Hydrochloride for animals as described in claim 1, feature exist
In：The slow-released carrier is the combination of cellulose family carrier and glue class two kinds of carriers of carrier, and cellulose family carrier and glue class carry
The quality proportioning of body is 2: 1；Wherein, cellulose family carrier is sodium carboxymethylcellulose and/or hydroxypropyl methyl cellulose, glue class
Carrier is gelatin and/Arabic gum.
3. the compound sustained-released injection of gentamicin sulphate-Lincomycin Hydrochloride for animals as described in claim 1, feature exist
In：The stabilizer is the combination of one or more of polyethylene glycol 200, polyethylene glycol 400, Macrogol 600.
4. the compound sustained-released injection of gentamicin sulphate-Lincomycin Hydrochloride for animals as described in claim 1, feature exist
In：The analgesic is benzyl alcohol.
5. a kind of any one compound sustained-released injection of gentamicin sulphate-Lincomycin Hydrochloride for animals of such as claim 1 ~ 4
The preparation method of liquid, which is characterized in that include the following steps：
（1）, by stabilizer be added partial syringe water in, stirring and dissolving；It is big that two kinds of main ingredient sulfuric acid celebratings are then added in system
Mycin and Lincomycin Hydrochloride, stirring and dissolving to clear obtain system A；
（2）, slow-released carrier is added in system A, stirring obtains system B to being completely dissolved；
（3）, analgesic is dissolved in organic solvent, obtain system C；
（4）, by after system C and system B mixings, water for injection is settled to 100g can to get gentamicin sulphate for animals-hydrochloric acid woods
The compound sustained-released injection of mycin.
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| CN111437249A (en) * | 2020-04-21 | 2020-07-24 | 上海公谊药业有限公司 | Compound gentamicin sulfate injection and preparation method and application thereof |
| CN116785237A (en) * | 2023-02-17 | 2023-09-22 | 安徽农业大学 | Compound gentamicin injection and preparation method and application thereof |
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