CN106344598A - procaine benzylpenicillin-dihydrostreptomycin sulfate oil suspension and preparation method thereof - Google Patents

procaine benzylpenicillin-dihydrostreptomycin sulfate oil suspension and preparation method thereof Download PDF

Info

Publication number
CN106344598A
CN106344598A CN201610953770.7A CN201610953770A CN106344598A CN 106344598 A CN106344598 A CN 106344598A CN 201610953770 A CN201610953770 A CN 201610953770A CN 106344598 A CN106344598 A CN 106344598A
Authority
CN
China
Prior art keywords
oil
oil suspension
procaine benzylpenicillin
dihydrostreptomycin sulfate
mixture
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Withdrawn
Application number
CN201610953770.7A
Other languages
Chinese (zh)
Inventor
杨海涵
吴学渊
胡婷婷
唐华侨
李超
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Chengdu Qiankun Veterinary Pharmaceutical Co Ltd
Original Assignee
Chengdu Qiankun Veterinary Pharmaceutical Co Ltd
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Chengdu Qiankun Veterinary Pharmaceutical Co Ltd filed Critical Chengdu Qiankun Veterinary Pharmaceutical Co Ltd
Priority to CN201610953770.7A priority Critical patent/CN106344598A/en
Publication of CN106344598A publication Critical patent/CN106344598A/en
Withdrawn legal-status Critical Current

Links

Classifications

    • 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
    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
    • A61K31/7028—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages
    • A61K31/7034—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages attached to a carbocyclic compound, e.g. phloridzin
    • A61K31/7036—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages attached to a carbocyclic compound, e.g. phloridzin having at least one amino group directly attached to the carbocyclic ring, e.g. streptomycin, gentamycin, amikacin, validamycin, fortimicins
    • 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
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
    • A61K31/425—Thiazoles
    • A61K31/429—Thiazoles condensed with heterocyclic ring systems
    • A61K31/43—Compounds containing 4-thia-1-azabicyclo [3.2.0] heptane ring systems, i.e. compounds containing a ring system of the formula, e.g. penicillins, penems
    • 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
    • A61K47/44—Oils, fats or waxes according to two or more groups of A61K47/02-A61K47/42; Natural or modified natural oils, fats or waxes, e.g. castor oil, polyethoxylated castor oil, montan wax, lignite, shellac, rosin, beeswax or lanolin
    • 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
    • A61K9/10—Dispersions; Emulsions

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Oil, Petroleum & Natural Gas (AREA)
  • Molecular Biology (AREA)
  • Dispersion Chemistry (AREA)
  • Medicinal Preparation (AREA)

Abstract

The invention provides procaine benzylpenicillin-dihydrostreptomycin sulfate oil suspension. Every 100mL of the suspension comprises the following raw materials and auxiliary materials: 20g of procaine benzylpenicillin, 20g of dihydrostreptomycin sulphate, 1g of a surfactant, 0.5-1g of a colloid protecting agent, 2-5g of a suspending agent, 0.005-0.1g of an antioxidant, and the balance of oil phase. The procaine benzylpenicillin-dihydrostreptomycin sulfate oil suspension provided by the invention is high in deposition volume ratio, good in nozzle cleaner property and re-dispersibility property, free of quality degradation after being stored for 3 months in an environment of 4-60 DEG C, stable in quality and good in clinical application prospect.

Description

A kind of procaine benzylpenicillin-dihydrostreptomycin sulfate oil suspension and its preparation Method
Technical field
The invention belongs to field of veterinary is and in particular to a kind of procaine benzylpenicillin-dihydrostreptomycin sulfate oil suspension And preparation method thereof.
Background technology
Procaine benzylpenicillin is the procaine salt of penicillin, and its Antibacterial Constituents is penicillin.Penicillin is to molten The Streptococcus such as courageous and upright streptococcus, streptococcus pneumoniae and do not produce the staphylococcuses of penicillinase, Clostridium, digestion chain Anaerobe such as coccus and B. melaninogenicus etc. has good antibacterial activity, in addition Diplococcus gonorrhoeae, Neisseria meningitidis, white Larynx corynebacterium, Bacillus anthraciss, Actinomyces bovises, Streptobacillus moniliformiss, Listerella, leptospira and treponemal Body is also to penicillin-susceptible.The antimicrobial spectrum of procaine benzylpenicillin is identical with penicillin with the mechanism of action, is all thin by suppression Bacterium Cell wall synthesis play bactericidal action.
, because half-life short Metabolism Excretion is fast, the drug action time is short for penicillin, is to reach therapeutic effect during clinical treatment Need multiple dosing.Procaine benzylpenicillin is benzathine penicillin, compensate for this shortcoming of penicillin well.
Dihydrostreptomycin sulfate, belongs to aminoglycoside antibioticss, by disturbing bacterioprotein building-up process, causes conjunction Become abnormal protein, hinder the protein release of synthesis, bacterial cell membrane permeability in addition also can be made to strengthen and lead to The leakage of important physiologically substance, finally causes bacterial death.Dihydrostreptomycin sulfate is to tubercule bacillus and multiple Gram-negative Bacillus has antibacterial action.Effect to the majority gram-positive cocci such as staphylococcus aureuses is poor.Streptococcus, P. aeruginosa Bacterium and anaerobe are to this product intrinsic resistance.
Oil suspension is that insoluble drug is scattered in the heterogeneous liquid preparation formed in oil phase, and its maximum feature is to make Drug treating time extend, reduce times for spraying, it is possible to decrease labor intensity and reduce to body stress.However, oil suspension The preparation of especially oil for injection suspensoid is more difficult, and physical stability to be obtained, syringeability and weight dispersibility preferably produce Product, determine that suitable supplementary product kind and consumption are very crucial, and, oil suspension is higher to storage environment requirement, improves its storage Depositing stability is also the factor needing in preparation process to consider.
Procaine benzylpenicillin-dihydrostreptomycin sulfate the suspensoid of document report is water suspension at present, and applicant exists Find in process of the test, can be occurred with the procaine benzylpenicillin-dihydrostreptomycin sulfate suspensoid of water preparation molten at 60 DEG C Solution, is changed into orange-yellow thick liquid, no dispersibility, quality is not good.Therefore it is badly in need of double hydrogen chains to procaine benzylpenicillin-sulphuric acid Mycin suspensoid improves.
Content of the invention
It is an object of the invention to provide a kind of procaine benzylpenicillin-dihydrostreptomycin sulfate oil suspension and its preparation Method.
The invention provides a kind of oil suspension, the every 100ml of described suspensoid contains following supplementary material: procaine penicillium sp Plain 20g, dihydrostreptomycin sulfate 20g, surfactant 1g, colloid protective agent 0.5-2g, suspending agent 2-5g, antioxidant 0.005-0.1g, balance of oil phase.
Wherein, described surfactant be span-80, tween 80, one or more mixing in soybean phospholipid Thing.
Wherein, described surfactant is grouped into by following groups: span-80 0.5g, soybean phospholipid 0.5g.
Wherein, described colloid protective agent is magnesium stearate, Magnesiumaluminumsilicate, one or more is mixed in aluminium stearate Compound；
Preferably, the consumption of colloid protective agent is 0.5-1g.
Wherein, described colloid protective agent is the aluminium stearate of 0.5g.
Wherein, described suspending agent is Poloxamer 188, polyethylene glycol 6000, sodium carboxymethyl cellulose, polyvinyl pyrrole At least one in alkanone k30；
Preferably, suspending agent is the polyethylene glycol 6000 of 2g.
Wherein, described oil phase is mixture, soybean oil and the benzene isopropyl myristate of soybean oil and benzyl benzoate Mixture or soybean oil and ethyl oleate mixture；Wherein, volumn concentration in described mixture for the soybean oil is 10-20%.
Wherein, described antioxidant is the butylated hydroxyarisol of 0.005-0.02g, the dimension of 0.01～0.02g The vitamin e of raw element c Petiolus Trachycarpi ester, the propylgallate of 0.05～0.1g or 0.05～0.075g.
Wherein, the every 100ml of described suspensoid contains following supplementary material: procaine benzylpenicillin 20g, dihydrostreptomycin sulfate 20g, surfactant 1g, colloid protective agent 0.5-1g, suspending agent 2-5g, antioxidant 0.005-0.1g, balance of volume hundred Divide the mixture than the soybean oil for 10-20%:80-90% and benzyl benzoate；
Preferably, the every 100ml of described suspensoid contains following supplementary material: the double hydrogen strepto- of procaine benzylpenicillin 20g, sulphuric acid Plain 20g, span-80 0.5g, soybean phospholipid 0.5g, aluminium stearate 0.5g, polyethylene glycol 6000 2g, the tert-butyl group are to hydroxyl Fructus Foeniculi Ether 0.005-0.02g, balance of percent by volume is the soybean oil of 20%:80% and the mixture of benzyl benzoate.
Present invention also offers the preparation method of above-mentioned oil suspension, comprise the steps:
Take oil phase, be heated to 60 DEG C -70 DEG C, add colloid protective agent, suspending agent, surfactant and antioxidant, stir Mix uniformly, add procaine benzylpenicillin, dihydrostreptomycin sulfate after cooling, stir, homogenizing, obtain final product.
The invention provides a kind of procaine benzylpenicillin-dihydrostreptomycin sulfate oil suspension, using specific adjuvant Under conditions of species and consumption proportion, the suspensoid sedimentation volume ratio that the present invention prepares is high, syringeability and weight dispersibility are good Good, and in 4 DEG C～60 DEG C environment, storage has no Quality Down for 3 months, steady quality.
Obviously, the above according to the present invention, according to ordinary technical knowledge and the customary means of this area, without departing from Under the premise of the present invention above-mentioned basic fundamental thought, modification, replacement or the change of other various ways can also be made.
The specific embodiment of form by the following examples, remakes further specifically to the above of the present invention Bright.But this scope being interpreted as the above-mentioned theme of the present invention should not be only limitted to Examples below.All based on the above of the present invention The technology realized belongs to the scope of the present invention.
Specific embodiment
It is described further with embodiment below, but the present invention is not limited to these embodiments.
The raw material that the present invention uses, equipment are known product, are obtained by buying commercially available prod.
In following embodiments, refer to volume ratio except being related to % during oil phase/solvent, remaining is percent weight in volume (w/v, g/ml).
The preparation of embodiment 1 oil suspension of the present invention
Take soybean oil 20ml, add benzyl benzoate 80ml, after heating (60 DEG C -70 DEG C) mix homogeneously, add colloid to protect Shield agent (aluminium stearate 0.5g) dissolving, stirs after adding suspending agent (polyethylene glycol 6000 2.0g) fusing, adds surface Activating agent (0.5g span-80+0.5g soybean phospholipid), antioxidant tertiary butyl p-hydroxyanisole 0.02g, add general after cooling Shandong caine penicillin 20g, dihydrostreptomycin sulfate 20g, stir, and homogenizing obtains final product 20% procaine benzylpenicillin -20% sulfur Didrothenat (Grunenthal) oil suspension.
Illustrate beneficial effects of the present invention below by way of test example:
1st, material
Procaine benzylpenicillin, dihydrostreptomycin sulfate, North China pharmacy group；Benzyl benzoate, Shanghai bright moon daily use chemicals have Limit company；PEG-4000, Aladdin reagent company limited；Poloxamer-188, the limited public affairs of Beijing phoenix gift international trade Department；Aluminium stearate, magnesium stearate, tween 80, the chemical reagent such as span-80, methanol, sodium dihydrogen phosphate, the limited public affairs of western Gansu Province chemical industry Department；Methanol, match is silent to fly generation that (Chinese) company limited, homogenizer, Shanghai Heng Chuan plant equipment company limited.
2nd, the detection method of suspensoid
With reference to " Chinese veterinary pharmacopoeia " requirement to suspension, check the procaine benzylpenicillin-sulfur of preparation using the following method Didrothenat (Grunenthal) suspension.
2.1 sedimentation volume ratio
Apparatus plug graduated cylinder measures test sample 50ml, close plug, firmly shakes 1min, writes down the beginning height h of suspended matter0, quiet Put 3 hours, write down the final height h of suspended matter, be calculated as follows:
Sedimentation volume ratio=h/h0
Sedimentation volume ratio is not less than 0.90.
2.2 syringeability
Take test sample, with No. 12 needle aspirate after shaking, in 1 minute, volume aspirated is no less than 2ml.
The centrifugation standard of 2.3 reference Emulsions, test sample is shaken with after the rotating speed centrifugation 15min of 4000r/min, Ying Yifen Dissipate.
3rd, the preparation of suspension
Take solvent appropriate, add surfactant, antioxidant, colloid protective agent dissolving in the ratio drafted, after cooling Add procaine benzylpenicillin, dihydrostreptomycin sulfate to stir, use homogenizer homogenizing, obtain final product.
The impact to oil suspension quality for the test example 1 solvent (oil phase)
Select soybean oil, Oleum Brassicae campestriss, Oleum Arachidis hypogaeae semen, Semen Maydis oil, white oil, ethyl oleate, benzyl benzoate, myristic acid isopropyl Ester, soybean oil-ethyl oleate (soybean oil of different volumes proportioning and ethyl oleate), soybean oil-benzyl benzoate (different volumes The soybean oil of proportioning and benzyl benzoate), soybean oil-isopropyl myristate (soybean oil of different volumes proportioning and Semen Myristicae Isopropyl propionate) as solvent, and matching surface activating agent span-80 (5%w/v, g/ml), antioxidant tertiary butyl are to hydroxyl fennel Fragrant ether (bha) (0.02%w/v), colloid protective agent aluminium stearate (1%w/v) and principal agent procaine benzylpenicillin (20%w/v)- Different suspensoids prepared by dihydrostreptomycin sulfate (20%w/v), investigate its sedimentation volume ratio, syringeability, the dispersion after centrifugation Situation, the results are shown in Table 1.
The suspensoid quality evaluation result of table 1 different solvents preparation
Solvent Sedimentation volume ratio Syringeability (ml) Redispersion after centrifugation
Soybean oil 0.98 1.8 Do not disperse
Oleum Brassicae campestriss 0.98 1.7 Do not disperse
Oleum Arachidis hypogaeae semen 0.98 17 Do not disperse
Semen Maydis oil 0.98 1.6 Do not disperse
White oil 0.98 1.7 Do not disperse
Ethyl oleate 0.87 1.8 Do not disperse
Benzyl benzoate 0.85 1.9 Do not disperse
Isopropyl myristate 0.86 1.9 Do not disperse
Soybean oil 50%+ ethyl oleate 50% 0.94 1.6 Do not disperse
Soybean oil 50%+ benzyl benzoate 50% 0.94 1.8 Do not disperse
Soybean oil 50%+ isopropyl myristate 50% 0.94 1.8 Do not disperse
Soybean oil 10%+ benzyl benzoate 90% 0.96 1.9 Do not disperse
Soybean oil 20%+ benzyl benzoate 80% 0.96 1.7 Do not disperse
Soybean oil 30%+ benzyl benzoate 70% 0.95 1.4 Do not disperse
Soybean oil 10%+ isopropyl myristate 90% 0.97 1.9 Do not disperse
Soybean oil 20%+ isopropyl myristate 80% 0.98 1.6 Do not disperse
Soybean oil 30%+ isopropyl myristate 70% 0.93 1.5 Do not disperse
Soybean oil 10%+ ethyl oleate 90% 0.98 1.9 Do not disperse
Soybean oil 20%+ ethyl oleate 80% 0.95 1.5 Do not disperse
Soybean oil 30%+ ethyl oleate 70% 0.91 1.4 Do not disperse
As shown in Table 1, the procaine benzylpenicillin-dihydrostreptomycin sulfate suspension syringeability of various solvents preparation and from Heavy dispersibility after the heart is poor, does not all meet " Chinese veterinary pharmacopoeia " regulation.Wherein, solvent is soybean oil and benzyl benzoate, meat Isopropyl myristate or ethyl oleate mixing, and soybean oil volume ratio account for total solvent 10-20% when, the procaine of preparation is blue or green Mycin-dihydrostreptomycin sulfate oil suspension syringeability is relatively preferable.
The impact to oil suspension quality for test example 2 surfactant
From conventional oiliness surface active agent tween -80, span-80 and lecithin as surfactant, solvent is (big Oleum Glycines 20%- benzyl benzoate 80% volume ratio), colloid protective agent (aluminium stearate 1%), (tert-butyl group is to hydroxyl for antioxidant Methoxybenzene 0.02%), procaine benzylpenicillin -20% dihydrostreptomycin sulfate suspension of preparation 20%.
Investigate its sedimentation volume ratio, syringeability, the deployment conditions after centrifugation, the results are shown in Table 2.
The suspensoid quality evaluation result of table 2 different surfaces activating agent preparation
As shown in Table 2,0.5% span-80 (w/v)+0.5% soybean phospholipid (w/v) is as surfactant, preparation mixed Suspension sedimentation volume ratio, syringeability, the heavy dispersibility after centrifugation are all preferable, meet " Chinese veterinary pharmacopoeia " regulation, and using other Heavy dispersibility after the suspensoid centrifugation of surfactant preparation is poor, does not meet " Chinese veterinary pharmacopoeia " regulation.
The impact to oil suspension quality for test example 3 colloid protective agent
It is respectively adopted aluminium stearate, the combination of magnesium stearate, Magnesiumaluminumsilicate and different quality proportioning as colloid protective agent, And press solvent (soybean oil 20%+ benzyl benzoate 80%), antioxidant (butylated hydroxyarisol 0.02%), live in surface Property agent (0.5% span-80+0.5% soybean phospholipid) preparation 20% procaine benzylpenicillin -20% dihydrostreptomycin sulfate mix Suspension.
Investigate its sedimentation volume ratio, syringeability, the deployment conditions after centrifugation, the results are shown in Table 3.
The suspensoid quality evaluation result of the different colloid protective agent preparation of table 3
As shown in Table 3, colloid protective agent consumption controls when 0.5-2% (w/v), the suspensoid sedimentation volume ratio of preparation, Heavy dispersibility after syringeability, centrifugation is all preferable, and especially when using aluminium stearate 0.5-1% (w/v), the suspensoid of preparation sinks Fall volume ratio, syringeability are optimal.And the dispersion again after the suspensoid centrifugation prepared during colloid protective agent consumption higher (5%w/v) Property poor, do not meet " Chinese veterinary pharmacopoeia " regulation.
The impact to oil suspension quality for test example 4 suspending agent
The dispersion experiment in soybean oil using single substance respectively, result shows Poloxamer 188, Polyethylene Glycol 6000th, sodium carboxymethyl cellulose, tetra- kinds of materials of Polyvinylpyrrolidone k30 dispersibility in soybean oil preferably, illustrates these four Material suitably uses as suspending agent, and uses dispersibility in soybean oil for the Macrogol 4000 poor.
The Poloxamer 188 of selection different amounts, polyethylene glycol 6000, sodium carboxymethyl cellulose, polyvinyl pyrrole respectively Alkanone k30, and press solvent (soybean oil 20%- benzyl benzoate 80% volume ratio), surfactant (0.5% span-80+ 0.5% soybean phospholipid), antioxidant (butylated hydroxyarisol be 0.02%w/v), (aluminium stearate is colloid protective agent 1%w/v), procaine benzylpenicillin -20% dihydrostreptomycin sulfate suspension of preparation 20%, investigates its sedimentation volume ratio, leads to Deployment conditions after pin, centrifugation, the results are shown in Table 4.
The suspensoid quality evaluation result of the different suspending agent preparation of table 4
Addition Sedimentation volume ratio Syringeability (ml) Redispersion after centrifugation
Poloxamer 188 2.0% 0.96 2.5 Easily disperse
Poloxamer 188 5.0% 0.96 2.6 Easily disperse
Poloxamer 188 8.0% 0.99 2.1 It is difficult to disperse
Polyethylene glycol 6000 2.0% 0.96 3.7 Easily disperse
Polyethylene glycol 6000 5.0% 0.97 3.5 Easily disperse
Polyethylene glycol 6000 8.0% 0.98 2.6 It is difficult to disperse
Sodium carboxymethyl cellulose 2.0% 0.97 3.0 Easily disperse
Sodium carboxymethyl cellulose 5.0% 0.93 2.2 Easily disperse
Sodium carboxymethyl cellulose 8.0% 0.93 1.9 It is difficult to disperse
Polyvinylpyrrolidone k30 2.0% 0.96 2.7 Easily disperse
Polyvinylpyrrolidone k30 5.0% 0.96 2.6 Easily disperse
Polyvinylpyrrolidone k30 8.0% 0.99 1.9 It is difficult to disperse
As shown in Table 4, using polyethylene glycol 6000, consumption be 2.0-5.0% (w/v) as suspending agent when, preparation mixed Suspension sedimentation volume ratio, syringeability, the heavy dispersibility after centrifugation are all preferable, the use of Polyethylene Glycol consumption are being especially 2.0w/v When, the suspensoid best results of preparation.Poloxamer 188 (2.0-5.0%), sodium carboxymethyl cellulose (2.0-5.0%) and poly- Vinylpyrrolidone (2.0%) also has certain suspending effect to this suspensoid.
The impact to oil suspension quality for test example 5 antioxidant
Respectively with vitamin c Petiolus Trachycarpi ester (0.01%-0.02%w/v), butylated hydroxyarisol (0.005%- 0.02%w/v), propylgallate (0.05%-0.1%w/v), vitamin e (0.05%-0.075%w/v) are as antioxidation Agent, solvent (soybean oil 20%- benzyl benzoate 80% volume ratio), surfactant (0.5% span-80+0.5% Semen sojae atricolor phosphorus Fat), procaine benzylpenicillin -20% dihydrostreptomycin sulfate of colloid protective agent (aluminium stearate is 1%w/v) preparation 20% mixes Suspension, blank (is added without antioxidant, places 12 hours in 60 DEG C of water-baths, result adds the suspension of antioxidant All meet quality standard regulation, placebo solution color burn, illustrate that wherein composition there occurs oxidation or degrades.
Therefore, the above-mentioned four kinds of materials of the present invention all suitably use in suspensoid of the present invention as antioxidant.Test example 6 The impact to oil suspension quality for the preparation technology
This test compares and for polyethylene glycol 6000 to mix (a) with oil phase, or is directly added into the suspending of homogenizing in oil phase Effect (b).
Specific experiment method is as follows:
Preparation technology a: take soybean oil 20ml, add benzyl benzoate 80ml, after heating (60 DEG C -70 DEG C) mix homogeneously, Add colloid protective agent (aluminium stearate 0.5g) dissolving, after adding suspending agent (polyethylene glycol 6000 2.0g) fusing, stirring is equal Even, add surfactant (0.5g span-80+0.5g soybean phospholipid), and add antioxidant tertiary butyl p-hydroxyanisole 0.02g, adds procaine benzylpenicillin 20g, dihydrostreptomycin sulfate 20g after cooling, stirs, homogenizing obtains final product 20% general Shandong Caine penicillin -20% dihydrostreptomycin sulfate oil suspension.
Preparation technology b: take soybean oil 20ml, add benzyl benzoate 80ml, after heating (60 DEG C -70 DEG C) mix homogeneously, Add colloid protective agent (aluminium stearate 0.5g) dissolving, add surfactant (0.5g span-80+0.5g soybean phospholipid), and Add antioxidant tertiary butyl p-hydroxyanisole 0.02g, add suspending agent (polyethylene glycol 6000 2.0g) stirring after cooling all Even, add procaine benzylpenicillin 20g, dihydrostreptomycin sulfate 20g, stir, homogenizing obtains final product 20% procaine penicillium sp Plain -20% dihydrostreptomycin sulfate oil suspension.
The results are shown in Table 5.
The suspensoid quality evaluation result of table 5 Different Preparation
Preparation technology Sedimentation volume ratio Syringeability Dispersibility after centrifugation
a 1.00 2.8 Easily disperse
b 0.80 1.5 It is difficult to disperse
It can be seen that, the suspensoid quality obtaining of preparation technology a is better than preparation technology b.
The stability test of test example 7 suspensoid of the present invention
The procaine benzylpenicillin that technique a in test example 6 is prepared-dihydrostreptomycin sulfate oil suspension, respectively It is placed in 4 DEG C, 25 DEG C, 40 DEG C and 60 DEG C of environment and places 3 months, with reference to Chinese veterinary pharmacopoeia with reference to procaine benzylpenicillin and sulphuric acid Streptomycin quality standard (Chinese veterinary pharmacopoeia committee. Republic of China Veterinary Pharmacopoeia: [s]. Beijing: Chinese agriculture Publishing house, 2005.12) measure the content of 20% procaine benzylpenicillin -20% dihydrostreptomycin sulfate injection, the results are shown in Table 6.
The stability test of table 6 suspensoid of the present invention
As shown in Table 6, suspension of the present invention is placed 3 months under 4-60 DEG C of environment, its sedimentation volume ratio, syringeability, from After the heart, redispersibility, procaine benzylpenicillin content, dihydrostreptomycin sulfate content are all preferable, and each group difference is inconspicuous, says Bright suspension stability of the present invention is good.
To sum up, the present invention is by the screening of specific supplementary product kind, consumption, obtained sedimentation volume ratio, syringeability, after centrifugation Redispersibility is good, the oil suspension of procaine benzylpenicillin and dihydrostreptomycin sulfate stable content, and potential applicability in clinical practice is good.

Claims (10)

1. a kind of oil suspension it is characterised in that: the every 100ml of described suspensoid contains following supplementary material: procaine benzylpenicillin 20g, dihydrostreptomycin sulfate 20g, surfactant 1g, colloid protective agent 0.5-2g, suspending agent 2-5g, antioxidant 0.005- 0.1g, balance of oil phase.
2. oil suspension according to claim 1 it is characterised in that: described surfactant be span-80, tween- 80th, one or more mixture in soybean phospholipid.
3. oil suspension according to claim 2 it is characterised in that: described surfactant is grouped into by following groups: Span-80 0.5g, soybean phospholipid 0.5g.
4. oil suspension according to claim 1 it is characterised in that: described colloid protective agent be magnesium stearate, silicic acid One or more mixture in magnalium, aluminium stearate；
Preferably, the consumption of colloid protective agent is 0.5-1g.
5. oil suspension according to claim 4 it is characterised in that: described colloid protective agent be 0.5g stearic acid Aluminum.
6. oil suspension according to claim 1 it is characterised in that: described suspending agent be Poloxamer 188, poly- second two At least one in alcohol 6000, sodium carboxymethyl cellulose, Polyvinylpyrrolidone k30；
Preferably, suspending agent is the polyethylene glycol 6000 of 2g.
7. oil suspension according to claim 1 it is characterised in that: described oil phase is soybean oil and benzyl benzoate The mixture of mixture, soybean oil and benzene isopropyl myristate or the mixture of soybean oil and ethyl oleate；Wherein, Semen sojae atricolor Volumn concentration in described mixture for the oil is 10-20%.
8. oil suspension according to claim 1 it is characterised in that: described antioxidant be 0.005-0.02g uncle BHA, the vitamin c Petiolus Trachycarpi ester of 0.01～0.02g, the propylgallate of 0.05～0.1g or 0.05～ The vitamin e of 0.075g.
9. oil suspension according to claim 1 it is characterised in that: the every 100ml of described suspensoid contains following supplementary material: Procaine benzylpenicillin 20g, dihydrostreptomycin sulfate 20g, surfactant 1g, colloid protective agent 0.5-1g, suspending agent 2-5g, Antioxidant 0.005-0.1g, balance of percent by volume is the soybean oil of 10-20%:80-90% and mixing of benzyl benzoate Compound；
Preferably, the every 100ml of described suspensoid contains following supplementary material: procaine benzylpenicillin 20g, dihydrostreptomycin sulfate 20g, span-80 0.5g, soybean phospholipid 0.5g, aluminium stearate 0.5g, polyethylene glycol 6000 2g, butylated hydroxyarisol 0.005-0.02g, balance of percent by volume is the soybean oil of 20%:80% and the mixture of benzyl benzoate.
10. the preparation method of oil suspension described in claim 1-9 any one, is characterized in that: comprise the steps:
Take oil phase, be heated to 60 DEG C -70 DEG C, add colloid protective agent, suspending agent, surfactant and antioxidant, stirring is all Even, add procaine benzylpenicillin, dihydrostreptomycin sulfate after cooling, stir, homogenizing, obtain final product.
CN201610953770.7A 2016-10-26 2016-10-26 procaine benzylpenicillin-dihydrostreptomycin sulfate oil suspension and preparation method thereof Withdrawn CN106344598A (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
CN201610953770.7A CN106344598A (en) 2016-10-26 2016-10-26 procaine benzylpenicillin-dihydrostreptomycin sulfate oil suspension and preparation method thereof

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
CN201610953770.7A CN106344598A (en) 2016-10-26 2016-10-26 procaine benzylpenicillin-dihydrostreptomycin sulfate oil suspension and preparation method thereof

Publications (1)

Publication Number Publication Date
CN106344598A true CN106344598A (en) 2017-01-25

Family

ID=57865190

Family Applications (1)

Application Number Title Priority Date Filing Date
CN201610953770.7A Withdrawn CN106344598A (en) 2016-10-26 2016-10-26 procaine benzylpenicillin-dihydrostreptomycin sulfate oil suspension and preparation method thereof

Country Status (1)

Country Link
CN (1) CN106344598A (en)

Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1517090A (en) * 2003-01-20 2004-08-04 王玉万 Animal use suspensoid injection or emulsion containing antibacterial medicine
WO2009049115A1 (en) * 2007-10-11 2009-04-16 University Of Maryland Methods for the treatment of viral conditions
CN101721366A (en) * 2010-01-13 2010-06-09 洛阳惠中兽药有限公司 Components and preparation method of beta-lactam injection
CN103301140A (en) * 2012-03-16 2013-09-18 重庆方通动物药业有限公司 Veterinary procaine penicillin-dihydrostreptomycin sulfate suspension injection and preparation method thereof
CN105726462A (en) * 2014-12-10 2016-07-06 瑞普（天津）生物药业有限公司 Compound procaine benzylpenicillin injectant for cow breasts (during dry period)

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1517090A (en) * 2003-01-20 2004-08-04 王玉万 Animal use suspensoid injection or emulsion containing antibacterial medicine
WO2009049115A1 (en) * 2007-10-11 2009-04-16 University Of Maryland Methods for the treatment of viral conditions
CN101721366A (en) * 2010-01-13 2010-06-09 洛阳惠中兽药有限公司 Components and preparation method of beta-lactam injection
CN103301140A (en) * 2012-03-16 2013-09-18 重庆方通动物药业有限公司 Veterinary procaine penicillin-dihydrostreptomycin sulfate suspension injection and preparation method thereof
CN105726462A (en) * 2014-12-10 2016-07-06 瑞普（天津）生物药业有限公司 Compound procaine benzylpenicillin injectant for cow breasts (during dry period)

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
段新华 等: "普鲁卡因青霉素-硫酸双氢链霉素混悬液在猪体内的药物动力学", 《动物医学进展》 *

Similar Documents

Publication Publication Date Title
CN104127419B (en) A kind of stable Cefquinome sulfate oil suspension type injection
CN106265506B (en) Amoxicillin colistin sulfate oil suspension and preparation method thereof
US11980186B2 (en) Preparation method of eucalyptol emulsion and application thereof in biopesticides
CN106344509B (en) Cefquinome sulfate oil suspension and preparation method thereof
CN109044970A (en) A kind of cefquinome sulfate injection and preparation method thereof
CN105919941A (en) Composition containing amoxicillin and potassium clavulanate, and preparation method thereof
CN107049943B (en) Ceftiofur hydrochloride injection for dairy cattle and preparation method thereof
CN101804051B (en) Liposome injection of pharmaceutical composition of amoxicillin sodium and clavulanate potassium
CN100408032C (en) Stable injection docetaxel
CN106265505B (en) A kind of amoxicillin and clavulanate potassium oil suspension and preparation method thereof
CN106344598A (en) procaine benzylpenicillin-dihydrostreptomycin sulfate oil suspension and preparation method thereof
CN108619097A (en) A kind of anti-oxidant complex liposome of efficient anticancer
CN106420608A (en) Oil suspension with procaine benzylpenicillin and method for preparing oil suspension
CN102058545B (en) Meropenem freeze-dried preparation for injection and preparation method thereof
CN112971001A (en) Efficient composite mildew inhibitor for feed and preparation method thereof
CN106420606A (en) Ceftiofur hydrochloride suspension and preparation method thereof
CN104069266A (en) Plant essential oil composition for veterinary use
CN101756899A (en) Valnemulin nano-emulsion antibacterial medicine preparation
CN104706636A (en) Albendazole preparation and preparation method thereof
CN106727567A (en) A kind of Amoxicillin Enrofloxacin oil suspension and preparation method thereof
CN109431999B (en) Nano self-microemulsion, veterinary drug nano self-microemulsion and preparation method and application thereof
CN106420609A (en) Amoxicillin oil suspension and preparation method thereof
CN105853352B (en) A kind of suspension composition and preparation method thereof containing pranoprofen
TW202102264A (en) Novel method for producing lecithin organogel
AU2010101089B4 (en) Parasiticidal Composition

Legal Events

Date Code Title Description
C06 Publication
PB01 Publication
SE01 Entry into force of request for substantive examination
SE01 Entry into force of request for substantive examination
WW01 Invention patent application withdrawn after publication
WW01 Invention patent application withdrawn after publication

Application publication date: 20170125