CN1533770A - Saspension injection containing benzimidazole kind vermifuge - Google Patents
Saspension injection containing benzimidazole kind vermifuge Download PDFInfo
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Abstract
A suspension injection containing benzimidazole anthelmintic is prepared from abamectin or ivermectin (0.1-6 wt%), propanethio imidazole sulfoxide or oxfendazole (1-40), dispersing medium and assistant through dissolving ivermectin or abamectin in formaldehyde glycerine, adding propanetriol, stirring, adding water, stirring, adding propanethio imidazole sulfoxide or oxfendazole, stirring, homogenizing and adding the water for injection and assistant.
Description
Technical field
The present invention is a kind of animal use suspensoid injection that contains the benzimidazole anthelmintic drug, and the active ingredient of forming injection is albendazole sulfoxide (Albendazole oxide) or oxfendazole (Oxfendazole) or the hydrochlorate or the lactate that are formed by them; Also can add anthelmintic drug such as Macrolide in the preparation and form the compound recipe suspensoid injectio, but also oral administration of this suspensoid.
Background technology
Albendazole sulfoxide and oxfendazole are the benzimidazole anthelmintic drug, and they all have and well kill effect parasitizing the intravital nematicide of animal or human, trematodiasis and cestode.Commercially available product mainly is powder, tablet and oral administration mixed suspension.That describes among patent CN1383821A and the CN1376467A contains albendazole sulfoxide or contains oxfendazole's veterinary injection, comprising suspensoid, but in the patent to its concrete forms and preparation method does not have clear and definite description.
The preparation of suspensoid injectio is different from general solution type injection agent, its technology of preparing is complicated, kind and content for the content of the active ingredient of forming preparation and granular size, liquid dispersion medium kind and proportion, suspending agent, and other auxiliary agent whether add (as non-ionic surface active agent etc.) all have strict requirement, especially active ingredient using dosage determine must depend on the pharmacokinetics experiment and clinical experiment just can be clear and definite.Therefore, the present invention is actual to be the extension of CN1383821A and CN1376467A patent, and both the present invention had further determined the composition and the using method of albendazole sulfoxide suspensoid injectio or oxfendazole's suspensoid injectio.
The present invention has further filtered out the best of breed of active ingredient on the basis of CN1383821A and CN1376467A patent, filtered out the best of breed of disperse medium.Preferred Albendazole oxide monohydrochloride and albendazole sulfoxide micropowder (fineness is less than 50 μ m) combination, with 1,2-propylene glycol or 1,2-propylene glycol/formal glycerine (1～5: 1) be disperse medium, preparation contains the molten outstanding injection of albendazole sulfoxide, a part of albendazole sulfoxide in the said preparation (with the bonded part of HCl) exists with dissolved state, another part albendazole sulfoxide exists with the micropowder state, therefore, said preparation adopts the injection system administration, promptly have quick-acting effects, have slow release (long-acting) effect again, this is that preparation of the present invention is on forming and the prominent features aspect the clinical drug effect.Principle the present invention is also preferred in view of the above contains the preparation of following compositions.
1, the compositions of levamisole hydrochloride and albendazole sulfoxide micropowder or oxfendazole's micropowder.
2, the ternary composition of levamisole hydrochloride and Albendazole oxide monohydrochloride and albendazole sulfoxide micropowder.
3, the ternary composition of levamisole hydrochloride and oxfendazole chloride and oxfendazole's micropowder.
4, the ternary composition of levamisole hydrochloride and albendazole sulfoxide micropowder and ivermectin class anti-parasite medicine.
5, the ternary composition of levamisole hydrochloride and oxfendazole's micropowder and ivermectin class anti-parasite medicine.
6, the binary composition of oxfendazole's micropowder or albendazole sulfoxide micropowder and ivermectin class anti-parasite medicine.
Being used to disperse the suitable disperse medium of above compositions is 1,2-propylene glycol, 1,2-propylene glycol/formal glycerine, 1,2-glycol/propane triol/water, formal glycerine/glycerol/water, glycerol/dimethyl acetylamide, glycerol/N-methyl-ketopyrrolidine, 1,2-glycol/propane triol/N-methyl-ketopyrrolidine, 1,2-propylene glycol/N-methyl-ketopyrrolidine, optimum disperse medium is 1,2-propylene glycol or 1,2-propylene glycol/formal glycerine (1～5: 1) or 1,2-propylene glycol/N-methyl-ketopyrrolidine.
In preparation of the present invention, other anthelmintic drug such as Macrolide can dissolved state exists, and also can exist by the micropowder state, also can the solid dispersion microparticle state or microsphere state or microcapsule state be present in the preparation.
Summary of the invention
Albendazole sulfoxide suspensoid injectio of the present invention or oxfendazole's suspensoid injectio is characterized in that preparation consists of:
A, active ingredient 2～40% (W/V)
B, suspending agent 0～15% (W/V)
C, local pain palliative 0.5～2% (V/V)
D, non-ionic surface active agent 0～20% (V/V)
E, liquid dispersion medium to 100% (V/V)
The suspensoid of being made up of albendazole sulfoxide or oxfendazole and other anthelmintic of the present invention is characterized in that preparation consists of:
A, albendazole sulfoxide or oxfendazole 2～40% (W/V)
B, other anthelmintic drug 0.1～20% (W/V)
C, suspending agent 0～15% (W/V)
D, local pain palliative 0～2% (V/V)
E, non-ionic surface active agent 0～20% (V/V)
F, liquid dispersion medium to 100% (V/V)
Described other anthelmintic drug comprises: Macrolide anthelmintic drug (avilamycin abamectin, ivermectin ivermectin, road draw rhzomorph doramectin, moxidectin moxidectin, Ai Purui rhzomorph eprinomectin, 4"-Deoxy-4"-epi-methylaminoavermectin B1 emamectin), anticoccidial class medicine (sulfonamides and Trimethoprim class, quinolones, enemy restrain the sharp diclazuril of pearl, the sharp toltrazuril of many piperazines pearl, Radix Dichroae ketone), levamisole hydrochloride, fluorine worm nitrile.
Described suspending agent comprises: carboxymethyl cellulose (sodium), methylcellulose, sodium polyacrylate, molecular weight be greater than 1000 Polyethylene Glycol (PEG), polyvinylpyrrolidone (PVP), polyvinyl alcohol (PVA), xanthan gum, but above suspending agent more than one use together.
The preferred chlorobutanol of described local pain palliative, benzyl alcohol, tetracaine hydrochloride or lignocaine.
Described ionic surfactant pack is drawn together: polyoxyethylene-type surfactant, EPE polyol EPE, polyoxyethylene aliphatic alcohol ether and polyethenoxy alkylphenols: preferred best non-ionic surface active agent is: polyoxyethylene sorbitan fatty acid ester (Tween series), sorbitan fatty acid ester (Span series), castor oil polyoxyethylene ether (EL series) and alkylphenol polyoxyethylene (OP series) surfactant, they can use separately, but also two or more unites use.
Described liquid dispersion medium is the organic solvent of water and good biocompatibility; Preferred water, 1,2-propylene glycol, glycerol, formal glycerine, but these organic solvents one or more use with water.Preferred synthetic or extract from plant fatty acid ester material or triglyceride material are used for the preparation of oil suspending agent.
The compound preparation that preferably contains albendazole sulfoxide and ivermectin is characterized in that consisting of:
A, albendazole sulfoxide 10～20% (W/V)
B, ivermectin 1～5% (W/V)
C, suspending agent 0.2～10% (W/V)
D, benzyl alcohol 1% (V/V)
E, formal glycerine or 1,2-propylene glycol 10～40% (V/V)
F, glycerol 0～40% (V/V)
g、Tween-80???????????????????0～6％(V/V)
H, water for injection to 100% (V/V)
The further compound preparation of selecting that contains albendazole sulfoxide and ivermectin is characterized in that its composition, preparation method and using method are as follows:
(1) preparation is formed: a, albendazole sulfoxide micropowder 20% (W/V)
B, ivermectin or avilamycin 2% (W/V)
C, PVP or PEG or HCO 2～10% (W/V)
D, benzyl alcohol 1% (V/V)
E, formal glycerine 10% (V/V)
F, glycerol 20～40% (V/V)
g、Tween-80??????????????0～2％(V/V)
H, water for injection to 100% (V/V)
(2) preparation method: ivermectin or avilamycin are dissolved with formal glycerine, add glycerol, stirring and evenly mixing adds a spot of water for injection, behind the stirring and evenly mixing, add the albendazole sulfoxide micropowder, after the infiltration, add residue water for injection and auxiliary agent to final volume, homogenize, promptly.Or ivermectin or avilamycin and PVP, PEG or HCO be prepared into solid dispersion earlier; The albendazole sulfoxide micropowder is soaked into formal glycerine and glycerol, add water for injection after, add PVP or PEG or HCO/ ivermectin or avilamycin solid dispersion again, behind the mixing, add or do not add Tween-80, promptly.
(3) using method: above preparation is applicable to the animal parasitosis control.Has the effect that parasitizes the intravital nematicide of animal, distoma hepaticum, part cestode and epizoa (demodicid mite, Ticks, louse, fly larvae etc.) of killing.Using dosage and using method are this agent of subcutaneous injection 1ml/20 kg body weight.
The present invention preferably contains the injection of oxfendazole and ivermectin, and its preparation is formed and preparation method is:
(1) preparation is formed:
A, oxfendazole 20% (W/V)
B, ivermectin or avilamycin 2% (W/V)
C, PEG or PVP or HCO 2～10% (W/V)
D, benzyl alcohol 1% (V/V)
E, glycerol 10～40% (V/V)
F, formal glycerine 10～30% (V/V)
g、Tween-80????????????????????0～6％(V/V)
H, water for injection to 100% (V/V)
(2) preparation method: ivermectin or avilamycin are dissolved with formal glycerine, add glycerol, mixing adds a small amount of water for injection, behind the stirring and evenly mixing, adds oxfendazole's micropowder, adds remaining media and auxiliary agent again to final volume, homogenizes, promptly.Or, adding water for injection afterwards with oxfendazole's usefulness formal glycerine and glycerol infiltration, the solid dispersion that adds ivermectin or avilamycin and PVP, PEG behind the mixing or form with HCO homogenizes, promptly.
(3) using method: this agent is used for the animal anthelmintic, subcutaneous injection 1ml/30 kg body weight.
Simple organic solvents such as 2-propylene glycol are disperse medium with 1, and preparation contains albendazole sulfoxide or oxfendazole's suspensoid, and have the following advantages: 1, active ingredient is uniformly dispersed, good stability, long shelf-life; 2, flowability and syringeability are good, can prepare the preparation of active ingredient content higher (reaching more than 40%), and therefore, injection volume (volume) is little, and zest is little, and is easy to use.Therefore, the present invention is preferred especially, and organic solvents such as 2-propylene glycol are disperse medium merely with 1, and preparation contains albendazole sulfoxide or oxfendazole's suspensoid, and this suspensoid is composed as follows:
A, albendazole sulfoxide micropowder or oxfendazole's micropowder 10～30% (W/V);
B, Macrolide anti-parasite medicine 0～6% (W/V) or contain the solid dispersion 0～15% (W/V) of Macrolide anti-parasite medicine/HCO;
C, benzyl alcohol or chlorobutanol 0～2% (V/V);
D, 1,2-propylene glycol, formal glycerine, glycerol, Polyethylene Glycol, glycerol triacetate, benzyl benzoate or hot capric acid triglyceride, or they more than one unite use to 100% (V/V);
E, also can add levamisole hydrochloride or other anthelmintic of 5～20% (W/V);
F, also can add non-ionic surface active agent and suspending agent.
Preferred especially Albendazole oxide monohydrochloride of the present invention or oxfendazole chloride and albendazole sulfoxide or oxfendazole are combined into molten outstanding injection or oral molten outstanding injection, said preparation adopts the administration of subcutaneous injection mode, its outstanding feature is promptly have quick-acting effects, has slow release (long-acting) effect again.This molten outstanding agent is composed as follows:
A, Albendazole oxide monohydrochloride or oxfendazole chloride 2～25% (W/V);
B, albendazole sulfoxide micropowder or oxfendazole's micropowder 2～25% (W/W);
C, chlorobutanol 0～2% (V/V);
D, disperse medium comprise water, 1,2-propylene glycol, glycerol, Polyethylene Glycol, formal glycerine, glycerol triacetate, benzyl benzoate or hot capric acid triglyceride, or they more than one unite use to 100% (V/V);
E, also can add suspending agent or non-ionic surface active agent;
F, also can add 5～20% levamisole hydrochloride.
Preparation of the present invention is applicable to the control of animal parasitic worm disease, be particularly useful for the control of the parasitic disease due to pig, cattle, sheep nematicide, trematodiasis, cestode and the larva thereof, using dosage is 0.5～20mg/ kg body weight, preparation of the present invention is used to prevent and treat humans and animals trichonematosis, cerebral echinococcosis and cenurus cerebralis disease, excellent.
The specific embodiment
Demonstrate preparation of the present invention below, but example does not limit claim scope of the present invention, claim scope promptly of the present invention is not limited only to example.
Example 1, contain the injection of 20% albendazole sulfoxide and 2% ivermectin
Get the 1g ivermectin, with the dissolving of 5ml formal glycerine, add the 10ml glycerol, stir, add 13ml water, stir, add 10g albendazole sulfoxide micropowder, mixing adds 0.5ml benzyl alcohol and residue water for injection to final volume, homogenizes, promptly.
Example 2, contain the injection of 20% albendazole sulfoxide and 2% ivermectin
Get 1g ivermectin and 1.5g PVP, with the dissolving of 10ml formal glycerine, add 10g albendazole sulfoxide micropowder, mixing adds 10ml water, and stirring and evenly mixing adds 10ml water again, homogenizes, and adds residue water for injection to final volume, promptly.
Example 3, contain the injection of 20% albendazole sulfoxide and 2% ivermectin
Get the 1g ivermectin,, add the 10ml glycerol, stir with the dissolving of 5ml formal glycerine, add 10ml water, stirring and evenly mixing adds 10g albendazole sulfoxide micropowder, mixing, add 0.5ml benzyl alcohol and residue water for injection to final volume, homogenize, add 0.5ml Tween-80, stirring and evenly mixing promptly.
Example 4, contain the injection of 20% albendazole sulfoxide and 2% ivermectin
Get 1g ivermectin and 1.5g PVP, with the dissolving of 10ml formal glycerine, add 10ml water, stir rapidly, add 10ml water again, add 10g albendazole sulfoxide micropowder, mixing homogenizes, and adds the injection water to final volume, adds 1ml Tween-80 again, stirring and evenly mixing, promptly.
The preparation that example 1～4 is described is applicable to the animal parasitosis control, and 20 kg body weight injection 1ml reaches more than 95% adult of the intravital nematicide of parasitism, distoma hepaticum and the clean rate of driving of epizoa (demodicid mite, Ticks, louse, fly larvae etc.).
Example 5, contain the suspensoid injectio of 20% oxfendazole/2% ivermectin
Get the 4.4g ivermectin, with the dissolving of 20ml formal glycerine, add the 40ml glycerol afterwards, when stirring into the milky pasty state, add 50ml water, stirring and evenly mixing adds 40g oxfendazole micropowder, stirs, back adding 10ml glycerol homogenizes, stir gently, add the 2ml benzyl alcohol, add again 40ml water to final volume (200ml) promptly.This agent is used to prevent and treat animal parasitic nematode, cestode, trematodiasis and epizoa to be infected, and 30～40 kg body weight are injected this agent 1ml.
Example 6, contain the suspensoid of 30% albendazole sulfoxide
Get the albendazole sulfoxide micropowder 30g of fineness, add formal glycerine 30ml less than 30 μ m, 1,2-propylene glycol 20ml homogenizes, and adds 1, and the 2-propylene glycol is to final volume, mixing, promptly.
Example 7, contain 30% oxfendazole's suspensoid
Get the oxfendazole micropowder 30g of fineness, add formal glycerine 30ml less than 30 μ m, 1,2-propylene glycol 20ml homogenizes, and adds 1, and the 2-propylene glycol is to final volume, mixing, promptly.
Example 8, contain the molten outstanding agent of 20% albendazole sulfoxide/20% Albendazole oxide monohydrochloride
Get albendazole sulfoxide micropowder 20g, the Albendazole oxide monohydrochloride 20g of fineness, add 1 less than 30 μ m, 2-propylene glycol 40ml, formal glycerine 20ml homogenizes, promptly.
Example 9, contain 15% oxfendazole/15% oxfendazole chloride's molten outstanding agent
Get oxfendazole micropowder 15g, the oxfendazole chloride 15g of fineness less than 30 μ m, add formal glycerine 15ml, adding 1, the 2-propylene glycol homogenizes to 100ml, promptly.
Example 10, the molten outstanding injection of 16% albendazole sulfoxide/16% levamisole hydrochloride
Get levamisole hydrochloride 16g, add formal glycerine 16ml, 1,2-propylene glycol 48ml stirs, and the dissolving back adds 16g albendazole sulfoxide micropowder, homogenizes, promptly.
Example 11,16% albendazole sulfoxide/16% levamisole hydrochloride/0.6% ivermectin injection
Get the 16g levamisole hydrochloride, add the 14ml formal glycerine, 40ml1, the 2-propylene glycol, be stirred to basic dissolving after, add 16g albendazole sulfoxide micropowder, homogenize, transfer PH to 5～5.5 with acetic acid, add the 0.66g ivermectin afterwards, 0.4g sodium formaldehyde sulphoxylate or thiourea, be stirred to and homogenize, add 1, the 2-propylene glycol is to final volume, promptly.
Example 12,25% albendazole sulfoxide/0.7% ivermectin suspension
Get 25g albendazole sulfoxide micropowder, add about 60ml 1, the 2-propylene glycol disperses, and transfers PH to 5～5.5 with acetic acid, adds the 0.77g ivermectin afterwards, adds 1 again, and the 2-propylene glycol is to final volume.
Example 13, contain the molten suspension of 15% Albendazole oxide monohydrochloride/15% albendazole sulfoxide micropowder
Get Albendazole oxide monohydrochloride 15g, add formal glycerine 20ml, 1,2-propylene glycol 50ml stirs, and the dissolving back adds 15g albendazole sulfoxide micropowder (fineness is less than 30 μ m), stirring and evenly mixing, promptly.
Example 14, this example are the time-determination of plasma concentration after example 13 preparations are used for sheep
Laboratory animal is a sheep, and subcutaneous injection example 13 preparations, dosage are 10mg/kg b.w.; Matched group is oral albendazole 10mg/kg b.w.After the administration, different time is got blood, and separated plasma is with methanol extraction albumen and extraction albendazole sulfoxide, the centrifugal 10min of 10000 rpm then, quantitatively get supernatant, cross solid-phase extraction column, with methanol/hydrochloric acid solution eluting, the eluent evaporated in vacuo, quantitatively dissolve with small amount of methanol afterwards, carry out HPLC and analyze, the result is as follows:
| Sample time (h) | 0.5????1?????4?????6?????10????16???24????32????36????48????72 |
| Example 13 preparations | 1.13???1.6???2.2???2.5???2.5???1.9??1.5???1.1???0.96??0.3???0.1 |
| The matched group preparation | 0.32???0.57??1.17??1.27??1.43??1.3??0.99??0.66??0.45??0.19??0 |
Annotate: numeral is the meansigma methods (μ g/ml) of 6 sheep measurement results in the table.
The molten suspension of avilamycin of example 15,16% albendazole sulfoxide/16% levamisole hydrochloride/2.5%
Get levamisole hydrochloride 16g, add 1,2-propylene glycol 60ml stirs, and basic dissolving back adds 16g albendazole sulfoxide micropowder, 5g avilamycin/castor oil hydrogenated (1: 0.5～2) solid dispersion micropowder, homogenizes, and adds 1, and the 2-propylene glycol is to final volume.
This agent is used for cattle, the sick control of sheep parasite, and dosage is the 1ml/20 kg body weight, and nematicide and ectozoic control phase can reach more than 50 days, to drug resistance nematicide specially good effect.
The molten suspension of avilamycin of example 16,16% albendazole sulfoxide/16% levamisole hydrochloride/2.5%
Get 2.5g avilamycin, 3g PVP (k-30), under heating condition, make it dissolving with 3～5 times of amounts (W/V) ethanol, cooling and decompression under magnetic agitation afterwards adds about 50ml 1, the 2-propylene glycol when semi-solid preparation, continue to stir and reduced pressure treatment, after the complete Ex-all of ethanol, add 16g levamisole hydrochloride and 16g albendazole sulfoxide micropowder, homogenize, add 1, the 2-propylene glycol is to final volume.
This agent is used for cattle, the sick control of sheep parasite, and dosage is 1ml/20～30 kg body weight, and nematicide and ectozoic control phase can reach more than 50 days, to drug resistance nematicide specially good effect.
The molten suspension of avilamycin of example 17,16% albendazole sulfoxide/16% levamisole hydrochloride/2.5%
Get 2.5g avilamycin, 3g PVP (k-30), 1.5g castor oil hydrogenated, under heating condition, make it dissolving with 3～5 times of amounts (W/V) ethanol, cooling and decompression under magnetic agitation afterwards adds about 50ml 1, the 2-propylene glycol when semi-solid preparation, continue to stir and reduced pressure treatment, after the complete Ex-all of ethanol, add 16g levamisole hydrochloride and 16g albendazole sulfoxide micropowder, homogenize, add 1, the 2-propylene glycol is to final volume.
This agent is used for cattle, the sick control of sheep parasite, and dosage is 1ml/20～30 kg body weight, and nematicide and ectozoic control phase can reach more than 50 days, to drug resistance nematicide specially good effect.
The molten suspension of avilamycin of example 18,16% albendazole sulfoxide/16% levamisole hydrochloride/2.5%
Get 2.5g avilamycin, 3g PEG10000,1.5g castor oil hydrogenated, under heating condition, make it dissolving with 3～5 times of amounts (W/V) ethanol, cooling and decompression under magnetic agitation afterwards adds about 50ml 1, the 2-propylene glycol when semi-solid preparation, continue to stir and reduced pressure treatment, after the complete Ex-all of ethanol, add 16g levamisole hydrochloride and 16g albendazole sulfoxide micropowder, homogenize, add 1, the 2-propylene glycol is to final volume.
This agent is used for cattle, the sick control of sheep parasite, and dosage is 1ml/20～30 kg body weight, and nematicide and ectozoic control phase can reach more than 50 days, to drug resistance nematicide specially good effect.
The molten suspension of avilamycin of example 19,16% albendazole sulfoxide/16% levamisole hydrochloride/2.5%
Get 2.5g avilamycin, 3g PEG10000, under heating condition, make it dissolving with 3～5 times of amounts (W/V) ethanol, cooling and decompression under magnetic agitation afterwards adds about 50ml 1, the 2-propylene glycol when semi-solid preparation, continue to stir and reduced pressure treatment, after the complete Ex-all of ethanol, add 16g levamisole hydrochloride and 16g albendazole sulfoxide micropowder, homogenize, add 1, the 2-propylene glycol is to final volume.
This agent is used for cattle, the sick control of sheep parasite, and dosage is 1ml/20～30 kg body weight, and nematicide and ectozoic control phase can reach more than 50 days, to drug resistance nematicide specially good effect.
The molten suspension of avilamycin of example 20,16% albendazole sulfoxide/16% levamisole hydrochloride/2.5%
Get 2.5g avilamycin, 0.5～5g castor oil hydrogenated, under heating condition, make it dissolving with 3～5 times of amounts (W/V) ethanol, cooling and decompression under magnetic agitation afterwards adds about 50ml 1, the 2-propylene glycol when semi-solid preparation, continue to stir and reduced pressure treatment, after the complete Ex-all of ethanol, add 16g levamisole hydrochloride and 16g albendazole sulfoxide micropowder, homogenize, add 1, the 2-propylene glycol is to final volume.
This agent is used for cattle, the sick control of sheep parasite, and dosage is 1ml/20～30 kg body weight, and nematicide and ectozoic control phase can reach more than 50 days, to drug resistance nematicide specially good effect.
The molten suspension of avilamycin of example 21,16% albendazole sulfoxide/16% levamisole hydrochloride/2.5%
Get 2.5g avilamycin, 2.5g castor oil hydrogenated, 4gPVP, under heating condition, make it dissolving and fusing with the 2ml dimethyl acetylamide, under agitation cool off afterwards and add the injection water, homogenize, add 16g levamisole hydrochloride and 16g albendazole sulfoxide micropowder, homogenize, add 1,2-glycol/propane triol is to final volume.
This agent is used for cattle, the sick control of sheep parasite, and dosage is 1ml/20～30 kg body weight, and nematicide and ectozoic control phase can reach more than 50 days, to drug resistance nematicide specially good effect.
The molten suspension of avilamycin of example 22,16% albendazole sulfoxide/16% levamisole hydrochloride/2.5%
Get 5g avilamycin/castor oil hydrogenated (1: 1) solid dispersion micropowder, 16g levamisole hydrochloride and 16g albendazole sulfoxide micropowder, add 1, the 2-propylene glycol homogenizes to final volume, promptly.
This agent is used for cattle, the sick control of sheep parasite, and dosage is 1ml/20～30 kg body weight, and nematicide and ectozoic control phase can reach more than 50 days, to drug resistance nematicide specially good effect.
Claims (10)
1, a kind of suspensoid injectio that contains albendazole sulfoxide or oxfendazole is characterized in that preparation consists of:
A, active ingredient 2～40% (W/V)
B, suspending agent 0～15% (W/V)
C, local pain palliative 0.5～2% (V/V)
D, non-ionic surface active agent 0～20% (V/V)
E, liquid dispersion medium to 100% (V/V)
2, a kind of suspensoid of being made up of albendazole sulfoxide or oxfendazole and other anthelmintic is characterized in that preparation consists of:
A, albendazole sulfoxide or oxfendazole 2～40% (W/V)
B, other anthelmintic drug 0.1～20% (W/V)
C, suspending agent 0～15% (W/V)
D, local pain palliative 0～2% (V/V)
E, non-ionic surface active agent 0～20% (V/V)
F, liquid dispersion medium to 100% (V/V)
3, by claim 1 and 2 described preparations, it is characterized in that:
(1), described other anthelmintic drug comprises: Macrolide anthelmintic drug (avilamycin abamectin, ivermectin ivermectin, road draw rhzomorph doramectin, moxidectin moxidectin, Ai Purui rhzomorph eprinomectin, 4"-Deoxy-4"-epi-methylaminoavermectin B1 emamectin), anticoccidial class medicine (sulfonamides and Trimethoprim class, quinolones, enemy restrain the sharp diclazuril of pearl, the sharp toltrazuril of many piperazines pearl, Radix Dichroae ketone), levamisole hydrochloride, fluorine worm nitrile.
(2), described suspending agent comprises: carboxymethyl cellulose (sodium), methylcellulose, sodium polyacrylate, molecular weight be greater than 1000 Polyethylene Glycol (PEG), polyvinylpyrrolidone (PVP), polyvinyl alcohol (PVA), xanthan gum, castor oil hydrogenated (HCO), ethyl cellulose (EC), but above suspending agent more than one use together.
(3), the preferred chlorobutanol of described local pain palliative, benzyl alcohol, tetracaine hydrochloride or lignocaine.
(4), described ionic surfactant pack is drawn together: polyoxyethylene-type surfactant, EPE polyol EPE, polyoxyethylene aliphatic alcohol ether and polyethenoxy alkylphenols; Preferred best non-ionic surface active agent is: polyoxyethylene sorbitan fatty acid ester (Tween series), sorbitan fatty acid ester (Span series), castor oil polyoxyethylene ether (EL series) and alkylphenol polyoxyethylene (OP series) surfactant, they can use separately, but also two or more unites use.
(5), described liquid dispersion medium is the organic solvent of water or good biocompatibility; Preferred water or 1,2～propylene glycol, glycerol, formal glycerine, but these organic solvents one or more use with water, be used for the preparation of aqueous suspension.Preferred synthetic or extract from plant fatty acid ester material or triglyceride material are used for the preparation of oil suspending agent.
4, described by claim 2 and 3, it is characterized in that preferred preparation consists of:
A, albendazole sulfoxide micropowder 10～20% (W/V)
B, ivermectin or avilamycin 1～5% (W/V)
C, suspending agent 0.2～10% (W/V)
D, benzyl alcohol 1% (V/V)
E, formal glycerine or 1,2-propylene glycol 10～40% (V/V)
F, glycerol 0～40% (V/V)
g、Tween-80????????????????????????0～6％(V/V)
H, water for injection to 100% (V/V)
5, by the described preparation of claim 4, it is characterized in that preparation composition, preparation method and the using method selected are as follows:
(1) preparation is formed: a, albendazole sulfoxide micropowder 20% (W/V)
B, ivermectin or avilamycin 1.5～3.5% (W/V)
More than one use c, PVP or PEG or HCO or they together
1～10％(W/V)
D, benzyl alcohol 1% (V/V)
E, formal glycerine 10% (V/V)
F, glycerol 20～40% (V/V)
g、Tween-80??????????????????????????????0～2％(VN)
H, water for injection to 100% (V/V)
(2) preparation method: ivermectin or avilamycin are dissolved with formal glycerine, add glycerol, stirring and evenly mixing adds a spot of water for injection, behind the stirring and evenly mixing, add the albendazole sulfoxide micropowder, after the infiltration, add residue water for injection and auxiliary agent to final volume, homogenize, promptly.Or ivermectin or avilamycin and PVP or PEG or HCO be prepared into solid dispersion earlier; The albendazole sulfoxide micropowder is soaked into formal glycerine and glycerol, add water for injection after, add PVP or PEG or HCO/ ivermectin or avilamycin solid dispersion again, behind the mixing, add or do not add Tween-80, promptly.
(3) using method: above preparation is applicable to the animal parasitosis control.Has the effect that parasitizes the intravital nematicide of animal, distoma hepaticum, part cestode and epizoa (demodicid mite, Ticks, louse, fly larvae etc.) of killing.Using dosage and using method are this agent of subcutaneous injection 1ml/20 kg body weight.
6, described by claim 2 and 3, it is characterized in that the injection composition and the preparation method that preferably contain the oxfendazole are:
(1) preparation is formed: a, oxfendazole 20% (W/V)
B, ivermectin or avilamycin 2～3.5% (W/V)
C, PEG or PVP or HCO 1～10% (W/V)
D, benzyl alcohol 1% (V/V)
E, glycerol 10-40% (V/V)
F, formal glycerine 10～30% (V/V)
g、Tween-80???????????????????????????0～6％(V/V)
H, water for injection to 100% (V/V)
(2) preparation method: ivermectin or avilamycin are dissolved with formal glycerine, add glycerol, mixing adds a small amount of water for injection, behind the stirring and evenly mixing, adds oxfendazole's micropowder, adds remaining media and auxiliary agent again to final volume, homogenizes, promptly.Or, add water for injection afterwards with oxfendazole's usefulness formal glycerine and glycerol infiltration, and add the solid dispersion micropowder that ivermectin or avilamycin and PVP or PEG or HCO form behind the mixing, homogenize, promptly.
(3) using method: this agent is used for the animal anthelmintic, subcutaneous injection 1ml/30 kg body weight.
7, described by claim 1～3, it is characterized in that preferred preparation composition, preparation method and using method are as follows:
(1) preparation is formed:
A, albendazole sulfoxide or oxfendazole 10% (W/V)
B, ivermectin or avilamycin 0～1% (W/V)
C, PEG10000 or PVP 3～8% (W/V)
D, glycerol 10～40% (V/V)
E, water to 100% (V/V)
F, add a spot of non-ionic surface active agent in case of necessity, preferred Tween-80.
(2) preparation method: with the N-methyl-ketopyrrolidine dissolving of ivermectin or avilamycin with 1～1.5 times, add PEG or PVP afterwards, heat fused or dissolving, add water, after treating that ivermectin is separated out, add albendazole sulfoxide micropowder or oxfendazole's micropowder, add glycerol and water, promptly get the compound recipe suspension to final volume.
(3) using method: this agent can be used for the animal anthelmintic, and injectable also can orally use, and dosage is 1ml/10～25 kg body weight.
8, described by claim 1～3, it is characterized in that preferred preparation consists of:
A, albendazole sulfoxide micropowder or oxfendazole's micropowder 10～30% (W/V);
B, Macrolide anti-parasite medicine 0～6% (W/V) or Macrolide anti-parasite medicine/HCO solid dispersion (1: 0.3～3) micropowders 0～15% (W/V);
C, benzyl alcohol or chlorobutanol 0～2% (V/V);
D, 1,2-propylene glycol, formal glycerine, glycerol, Polyethylene Glycol, glycerol triacetate, benzyl benzoate or suffering-capric acid triglyceride, or they more than one unite use to 100% (V/V);
E, also can add levamisole hydrochloride or the anticoccidial class medicine or the organic phosphates anthelmintic drug of 5～20% (W/V);
F, also can add non-ionic surface active agent and suspending agent.
9, described by claim 1～3, it is characterized in that preparation consists of:
A, Albendazole oxide monohydrochloride or oxfendazole chloride 2～25% (W/V);
B, albendazole sulfoxide micropowder or oxfendazole's micropowder 2～25% (W/W);
C, chlorobutanol 0～2% (V/V);
D, disperse medium comprise water, 1,2-propylene glycol, glycerol, Polyethylene Glycol, formal glycerine, glycerol triacetate, benzyl benzoate or suffering-capric acid triglyceride, or they more than one compositions to 100% (V/V);
E, also can add suspending agent or non-ionic surface active agent;
F, also can add the levamisole hydrochloride of 5～20% (W/V).
10, by the described preparation of claim 1～3, it is characterized in that preferred water, 1,2-propylene glycol, glycerol, formal glycerine, Polyethylene Glycol, glycerol triacetate, benzyl benzoate, suffering-capric acid triglyceride, or they more than one compositions, the preparation that is used to contain the suspensoid of albendazole sulfoxide or contains oxfendazole's suspensoid; Also can add one or more other anthelmintics in the preparation, be prepared into compound preparation, preferred other anthelmintic comprises: avilamycin, ivermectin, road draw rhzomorph, moxidectin, Ai Purui rhzomorph, 4"-Deoxy-4"-epi-methylaminoavermectin B1, levamisole hydrochloride, fluorine worm nitrile, organic phosphates to drive (killing) worm medicine or anticoccidial class anti-parasite medicine, these anthelmintic drugs can exist by dissolved state in preparation, also can the micropowder state exist, also can the solid dispersion microparticle state or microsphere state or microcapsule state exist; Also can add non-ionic surface active agent, suspending agent, antioxidant or local pain palliative in the preparation; This suspensoid is applicable to animal parasitosis control, but also oral administration of injectable administration, and dosage is 0.5～20mg albendazole sulfoxide or oxfendazole/kg body weight.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNA031485375A CN1533770A (en) | 2003-03-26 | 2003-07-02 | Saspension injection containing benzimidazole kind vermifuge |
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN03120965 | 2003-03-26 | ||
| CN03120965.3 | 2003-03-26 | ||
| CNA031485375A CN1533770A (en) | 2003-03-26 | 2003-07-02 | Saspension injection containing benzimidazole kind vermifuge |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN1533770A true CN1533770A (en) | 2004-10-06 |
Family
ID=34314787
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CNA031485375A Pending CN1533770A (en) | 2003-03-26 | 2003-07-02 | Saspension injection containing benzimidazole kind vermifuge |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN1533770A (en) |
Cited By (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102258529A (en) * | 2011-04-29 | 2011-11-30 | 武汉回盛生物科技有限公司 | Compound ivermectin injection and preparation method thereof |
| CN102440996A (en) * | 2011-12-29 | 2012-05-09 | 郑国祥 | Compound albendazole suspension containing ivermectin nanoemulsion and preparation method thereof |
| CN103126782A (en) * | 2013-02-26 | 2013-06-05 | 内蒙古农牧业科学院 | Method for treating parasitic disease |
| CN103356714A (en) * | 2013-07-21 | 2013-10-23 | 山东中牧兽药有限公司 | Veterinary compound pharmaceutical composition containing albendazole and ivermectin |
| CN103432152A (en) * | 2013-08-22 | 2013-12-11 | 潍坊富邦药业有限公司 | Injection for repelling and killing internal and external parasites of livestock |
| CN104434970A (en) * | 2014-11-14 | 2015-03-25 | 山西双鹰动物药业有限公司 | Medicine for treating nematodosis and trematodiasis of cattle and sheep and preparation method of medicine |
| CN108524444A (en) * | 2018-05-04 | 2018-09-14 | 江西新天地药业有限公司 | A kind of compound albendazole tablets suspension solution agent and preparation method thereof |
-
2003
- 2003-07-02 CN CNA031485375A patent/CN1533770A/en active Pending
Cited By (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102258529A (en) * | 2011-04-29 | 2011-11-30 | 武汉回盛生物科技有限公司 | Compound ivermectin injection and preparation method thereof |
| CN102440996A (en) * | 2011-12-29 | 2012-05-09 | 郑国祥 | Compound albendazole suspension containing ivermectin nanoemulsion and preparation method thereof |
| CN102440996B (en) * | 2011-12-29 | 2013-04-24 | 郑国祥 | Compound albendazole suspension containing ivermectin nanoemulsion and preparation method thereof |
| CN103126782A (en) * | 2013-02-26 | 2013-06-05 | 内蒙古农牧业科学院 | Method for treating parasitic disease |
| CN103126782B (en) * | 2013-02-26 | 2016-06-29 | 内蒙古农牧业科学院 | A kind of Therapeutic Method of parasitic disease |
| CN103356714A (en) * | 2013-07-21 | 2013-10-23 | 山东中牧兽药有限公司 | Veterinary compound pharmaceutical composition containing albendazole and ivermectin |
| CN103356714B (en) * | 2013-07-21 | 2014-09-10 | 山东中牧兽药有限公司 | Veterinary compound pharmaceutical composition containing albendazole and ivermectin |
| CN103432152A (en) * | 2013-08-22 | 2013-12-11 | 潍坊富邦药业有限公司 | Injection for repelling and killing internal and external parasites of livestock |
| CN104434970A (en) * | 2014-11-14 | 2015-03-25 | 山西双鹰动物药业有限公司 | Medicine for treating nematodosis and trematodiasis of cattle and sheep and preparation method of medicine |
| CN108524444A (en) * | 2018-05-04 | 2018-09-14 | 江西新天地药业有限公司 | A kind of compound albendazole tablets suspension solution agent and preparation method thereof |
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