CN101987108A - Compound injection for repelling internal and external parasites of animal bodies and preparation method thereof - Google Patents
Compound injection for repelling internal and external parasites of animal bodies and preparation method thereof Download PDFInfo
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- CN101987108A CN101987108A CN 200910069942 CN200910069942A CN101987108A CN 101987108 A CN101987108 A CN 101987108A CN 200910069942 CN200910069942 CN 200910069942 CN 200910069942 A CN200910069942 A CN 200910069942A CN 101987108 A CN101987108 A CN 101987108A
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- ivermectin
- praziquantel
- repelling
- compound injection
- injection
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Abstract
The invention relates to a compound injection for repelling internal and external parasites of animal bodies and a preparation method thereof. The compound injection mainly consists of ivermectin and praziquantel. Ivermectin is a 16-membered macrolide specific medicine for preventing and treating the internal and external parasites of animal bodies and can specifically prevent and treat cardio-filaria and efficiently prevent and treat the internal parasites such as hookworm, roundworm, whipworm, bellyworm and the like and the external parasites such as Demodex folliculorum, acariasis, louse, flea and the like. Praziquantel is efficient to wireworm, trematode and cestode in the animal bodies. The worm-repelling spectrums of ivermectin and praziquantel are mutual complementary and the combination of the two medicines expands the worm-repelling spectrums and improves the worm-repelling effect at one time. The invention further provides a preparation method of the compound injection. The compound injection is used for hypodermic and has long drug-effect lasting time.
Description
Technical field
The invention belongs to the veterinary drug technical field, compound injection of particularly a kind of animal repelling endoparasite and ectoparasite and preparation method thereof.
Background technology
The anthelmintic drug developing history is long, and before more than 2000 years, first herbal Shennong's Herbal of China has been listed as more than 30 kind of anthelmintic drug altogether, and Radix Dichroae treating malaria and chinaberry reality, Omphalia, Rhizoma Osmundae etc. become in the world record the earliest and drive (killing) worm medicine.Anthelmintics such as Fructus Ulmus preparatium, the Fructus Evodiae, Radix Granati, wolf tooth, Semen Arecae, Semen Cucurbitae, Semen Torreyae are still using so far.
Thirties the 17th century, the Spaniard can treat malaria at Peru's discovery golden pheasant sodium (cinchona) bark, and this has opened a fan window for anti-parasite medicine to the modern pharmacology development.Isolated the main alkaloid-quinine (quinine) of red cinchona skin in 1820, quinine has been brought into play important function in for treatment and prevention of malaria in nearly twoth century.The success of nineteen forty-four chemosynthesis quinine, this is with New Times that modern age, chemical synthetic drug was opened anti-parasite medicine such as sulfanilamide.Along with the application of new technique and method, medicine for parasitic disease is brought in constant renewal in, and chemosynthesis and semisynthetic drug become anti-parasite medicine main flow and research direction.It is generally acknowledged that at present ideal anti-parasite medicine is: nontoxic, side effect; Broad-spectrum high efficacy; Cheap, easy to use; Do not influence immunity of organisms; Medicine and metabolite are free from environmental pollution.Also require noresidue for food animal with antiparasitic.The animal antiparasitic praziquantel of extensive use at present kills trematodiasis, cestode medicine as wide spectrum; Characteristics such as ivermectin (ivermectin) has efficiently, low toxicity, pest-resistant spectrum are wide, but poor to trematodiasis, cestode effect.For the further anthelmintic spectrum that enlarges, strengthen anthelminthic effect, the special compound injection of developing the two.
Compound injection component anthelminthic effect is introduced:
1, ivermectin (Ivermcctin): be the semi-synthetic Macrolide multicomponent antibiotic that produces by Avid kyowamycin (streptomyces avermitilis) fermentation.Mainly contain ivermectin B
1(B
1a+ B
1b) be not less than 93%, B wherein
1aMust not be less than 85%.Ivermectin B
1Promptly 22, the two hydrogen avilamycin B of 23-
1
[pharmacology]
(1) the pharmacodynamics ivermectin is novel wide spectrum, efficient, low toxicity antibiotics antiparasitic, and particularly nematicide and arthropod all have and well kill effect to endoparasite and ectoparasite.But it is invalid to cestode, trematodiasis and protozoacide.
The Macrolide antiparasitic is to nematicide and arthropodanly kill effect, is to increase the release of the inhibitory transmitter γ-An Jidingsuan (GABA) of polypide, and the Cl that opens glutamic acid control
-Passage strengthens neurolemma to Cl
-Permeability, thereby the transmission of block nerves signal, final neural paralysis makes muscle cell lose contractility, and causes polypide death.
Because trematodiasis and cestode are not to transmit mediator with GABA, and lack the Cl that is subjected to glutamic acid control
-Passage.So this class medicine is invalid to it.Mammiferous peripheral neurotransmitter is an acetylcholine, though GABA is distributed in the central nervous system, and owing to this class medicine is difficult for seeing through blood brain barrier, and minimum to its influence, just compare safety when therefore using.
The mechanism of this class drug influence parasite reproduction is also not clear, lays eggs but Ticks is reduced, and ruminates beastly nematicide worm's ovum paramophia and makes thread nematicide (male, female) sterile.
(2) pharmacokinetics of pharmacokinetics ivermectin because of poultry kind, dosage form is different with route of administration that notable difference arranged.With the plasma half-life is example, gives cattle, sheep intravenous injection 300 μ g/kg amount, t
1/2Though difference little (being respectively 2.8 days and 2.7 days), the plasma concentration of sheep are low be owing to apparent volume of distribution greater than due to the cattle.Ivermectin is drained very fast (t in the dog body
1/2=1.6～1.8 days), the half-life of pig reaches 4 days.
Dog is taken (100 μ g/kg) tablet orally, blood medicine peaking (40ng/mL) in 2～4h.Sanguis sus domestica medicine peak value time of advent, (0.5 day) for oral administration is faster than subcutaneous injection (2 days), but hypodermic bioavailability is more much higher than for oral administration, and the bioavailability when taking orally usually only is 41% of an injection.
The ivermectin of two kinds of different dosage forms (the special-purpose dosage form of paste and aqueous micella) is for oral administration to horse, blood medicine peak value time of occurrence, and not only (4～5h) is more faster than paste (15h), and bioavailability is also high for aqueous micella preparation.(paste only be the agent of aqueous micella 20%).
Absorb the back ivermectin and be distributed widely in body tissue, and the highest with concentration in liver and the fatty tissue.Ivermectin is oxidized to metabolite usually in liver.
Ivermectin through the accounting for more than 90% of defecate, only accounted for 0.5%～2% through homaluria in 5～6 days.
Dog, cat (by 6～12 μ g/kg amount) are used to prevent and treat dog heartworm microfilariae of ohchocerciasis and infect, and China can try out 50 μ g/kg interior oral administrations treatment heartworm microfilariae of ohchocerciasis insect infection (adult is invalid).Clinical trial confirms, the high dose ivermectin has efficiently the multiple parasite of dog, as subcutaneous injection 50 μ g/kg to ancylostoma caninum, ancylostoma braziliense, European ancylostoma caninum, 100 μ g/kg are to the dog whipworm, 200 μ g/kg to dog bend first ascarid adult and the fourth phase larva a splendid effect of driving is all arranged.To lion bow ascarid, by 200 μ g/kg amount, subcutaneous injection curative effect only 69%, for oral administration then reach 95%.Subcutaneous injection of this product, the Capillaria aerophila (200 μ g/kg), the Ovshinsky Ou Sile nematicide (400 μ g/kg) that dog are parasitized pulmonary also have splendid dispel effect.For oral administration or subcutaneous injection 200 μ g/kg, two week the back reuse once, to intestinal strongyloides intestinalis (the 3rd phase larva except) effective percentage 95%～100%.
Ivermectin infects also effective to some arthropod of dog, cat, dog, cat skin be injection 200 μ g/kg dosage down, two week the back reuse once can get rid of the infection of ear demodicid mite, acaricide, dog lung thorn demodicid mite.By 300 μ g/kg amount, logotype twice (2 weeks at interval) is also very effective to the mite infestationss of Ji chela.Treatment dog demodicidosis is preferably pressed 600 μ g/kg subcutaneous injection amounts, 7 days at interval. logotype 5 times.
The different adjuvants that contain in [drug interaction] ivermectin commodity preparation can influence the effect of medicine, contain the preparation that tween 80 is done adjuvant as sheep is for oral administration, when the ivermectin consumption reaches 4000 μ g/kg, still very safe, but if then make when doing adjuvant sheep continue to occur in 3 days ataxia and hemoglobinuria with propylene glycol.The U.S. contains tween 80, and to do the Ivermectin HCL injection of adjuvant be the special-purpose commodity preparations of equus, but can not be used for dog, otherwise also be absolutely unsafe.
3. praziquantel
Praziquantel is all effective to schistosomicide, cestode, cysticercosis, clonorchis sinensis, lung fluke, fasciloopsis.Can play two kinds of main pharmacological to polypide:
(1) contraction of tetanic property takes place and produces spastic paralysis in polypide muscle: behind the schistosomicide contact low concentration praziquantel only 20 second polypide tension force promptly increase, blood drug level reaches 1mg/L when above, polypide wink is strong contracture.The polypide muscle contraction may increase the permeability of polypide cell membrane with praziquantel, makes the intracellular calcium forfeiture relevant.
(2) infringement of polypide cortex participates in host immune function: praziquantel has rapidly and the obvious impairment effect the polypide cortex, cause the swelling of syncytium crust, cavity appears, form bulla, outstanding body surface, the rotten to the corn diabrosis of final epidermis, body secretion almost all disappears, and circular muscle and longitudinal muscle be dissolving successively rapidly also.In host, taking medicine back 15 minutes is visible polypide crust vacuolar degeneration.After cortex destroys, influence polypide and absorb and excretory function, the more important thing is its body surface antigen-exposed, thereby subject to host's immune attack, a large amount of eosinophilic granulocyte are adhered to the skin lesion place and are invaded, and impel polypide death.In addition, praziquantel can also cause that Secondary cases changes, and makes the depolarization of polypide pellicle, and the cortex alkaline phosphatase activities obviously reduces, and causes the picked-up of glucose to be suppressed, the endogenous glycogen depletion.Praziquantel also can suppress polypide nucleic acid and proteinic synthetic.
Pharmacokinetics:
The pharmacokinetics and the bioavailability of the quiet notes of cattle, intramuscular injection and praziquantel for oral administration
6 adult healthy cattlees are pressed 10mg/kg dosage single fast intravenous injection praziquantel, and 6 adult healthy cattlees carry out pharmacokinetics and bioavailability test according to the trial design method by the intramuscular injection of 10mg/kg dosage single, 30mg/kg dosage praziquantel for oral administration in addition.Utilize mass concentration, its detection of the former medicine of praziquantel in the high effective liquid chromatography for measuring blood plasma to be limited to 25 μ g/L.Compartment model the analysis showed that, data fit does not have the two Room open models of absorption during medicine after the quiet notes administration, its distribution half-life (t1/2 α), elimination half-life (t1/2 β), apparent volume of distribution (Vd), CLTB (ClB), area under the drug-time curve (AUC) are respectively (0.25 ± 0.03) h, (1.28 ± 0.20) h, (2.11 ± 0.38) L/kg, (1.14 ± 0.10) L/ (kgh) and (8.79 ± 0.74) mg/ (Lh).Data fit has the absorption one compartment open model during medicine of intramuscular injection, main pharmacokinetic parameters absorbs the half-life (t1/2ka), eliminate the half-life (t1/2ke), area under the drug-time curve (AUC), peak time (tmax), peak concentration (Cmax) and bioavailability (F) are respectively (0.40 ± 0.17) h, (4.65 ± 0.91) h, (6.85 ± 1.02) mg/ (Lh), (1.33 ± 0.52) h, (0.83 ± 0.08) mg/L and 77.93%, meeting after the administration for oral administration has the absorption one compartment open model, absorbs irregular, its pharmacokinetic parameters t1/2ka, t1/2ke, AUC, Cmax and F are respectively (1.08 ± 0.13) h, (6.81 ± 1.26) h, (8.51 ± 1.78) mg/ (Lh), (4.331.36) h, (0.70 ± 0.08) mg/L and 32.31%.The result shows that intramuscular administration absorbs good, and malabsorption for oral administration, the F of intramuscular injection is 2.5 times after for oral administration, difference is (P＜0.01) extremely significantly.
4. the progress of compound preparation
Macrocyclolactone lactone kind medicines such as ivermectin lay particular emphasis on intravital nematicide of animal and the entozoic segmental appendage class of skin parasite, but invalid to trematodiasis, cestode; Praziquantel is effective to the intravital nematicide of animal, trematodiasis, cestode, but invalid to the entozoic segmental appendage class of skin parasite.So the two anthelmintic spectrum is complementary, unites use and has enlarged the anthelmintic spectrum, has improved disposable anthelminthic effect.Compound ivermectin (ivermectin, the closantel sodium) listing of the Inner Mongol China emerging pharmaceutcal corporation, Ltd of AudioCodes in 2007.It can obviously increase the mitochondrial permeability of parasite, by the idol effect of the separating performance anthelmintic action to oxidative phosphorylation.Its distoma hepaticum to domestic animal, front and back dish trematodiasis and arthropodan larva have the extraordinary activity of killing, and enlarge the pest-resistant spectrum and the anthelmintic efficiency of compound preparation.In addition, because the Macrolide anti-parasite medicine is different with the mechanism of action between other anti-parasite medicine, thereby does not exist cross resistance between such medicine and other anti-parasite medicine, should rotate alternatively administered.
By the combination of two kinds of medicines, can reach the purpose of widening the anthelmintic spectrum, dosing time is driven away endoparasite and ectoparasite simultaneously, and is easy to use, simplified the anthelmintic pattern, satisfied clinical needs to a certain extent.
Summary of the invention
1, an object of the present invention is to provide a kind of compound injection that is used for the animal repelling endoparasite and ectoparasite, it is characterized in that prescription is made up of Macrolide anthelmintic, praziquantel.
2, another object of the present invention provides a kind of optimizing injection prescription, and this prescription is made up of ivermectin and praziquantel.It is characterized in that containing in every injection (5ml/ props up) ivermectin 0.03-0.06g, praziquantel 0.15-0.30g.The preferred ivermectin 0.05g of content, praziquantel 0.25g, subcutaneous injection dosage is 0.1ml/kg.
3, another object of the present invention also provides the preparation method of this compound injection.
The present invention realizes by following step:
The preparation method of compound preparation of the present invention comprises and takes by weighing recipe quantity crude drug ivermectin, praziquantel, use the propylene glycol heating for dissolving, add benzyl alcohol 7.5ml, add in the dispenser, slowly be diluted to 1000ml with an amount of refining Oleum Glycines, above-mentioned solution mix homogeneously, coarse filtration, fine straining, filling and sealing, sterilization, lamp inspection, packing warehouse-in.
The specific embodiment
Embodiment 1
(1) prescription (1000ml)
Ivermectin 6g, praziquantel 30g, benzyl alcohol 7.5ml, propylene glycol 150ml
(2) technology
Weighting raw materials ivermectin 6g, praziquantel 30g use the propylene glycol heating for dissolving, add the 7.5ml benzyl alcohol, add in the distributor, slowly be diluted to 1000ml with an amount of refining Oleum Glycines, above-mentioned solution mix homogeneously, coarse filtration, fine straining, filling and sealing, sterilization, lamp inspection, packing warehouse-in.
Embodiment 2
(1) prescription (1000ml)
Ivermectin 10g, praziquantel 50g, benzyl alcohol 7.5ml, propylene glycol 150ml
(2) technology
Weighting raw materials ivermectin 10g, praziquantel 50g use the propylene glycol heating for dissolving, add the 7.5ml benzyl alcohol, add in the distributor, slowly be diluted to 1000ml with an amount of refining Oleum Glycines, above-mentioned solution mix homogeneously, coarse filtration, fine straining, filling and sealing, sterilization, lamp inspection, packing warehouse-in.
Embodiment 3
(1) prescription (1000ml)
Ivermectin 12g, praziquantel 60g, benzyl alcohol 7.5ml, propylene glycol 150ml
(2) technology
Weighting raw materials ivermectin 10g, praziquantel 50g use the propylene glycol heating for dissolving, add the 7.5ml benzyl alcohol, add in the distributor, slowly be diluted to 1000ml with an amount of refining Oleum Glycines, above-mentioned solution mix homogeneously, coarse filtration, fine straining, filling and sealing, sterilization, lamp inspection, packing warehouse-in.
Embodiment 4:
Injection with the foregoing description 2 preparations is an example, carries out the clinical efficacy test, further specifies the therapeutic effect of medicine of the present invention.[contain ivermectin 0.05g, praziquantel 0.25g in every injection (5ml/ props up), subcutaneous injection dosage is 0.1ml/kg]
Selection medical history, 100 of the ill pigs that the state of an illness is suitable are divided into 2 groups at random, are respectively test group and matched group, 50 every group.Test group gives the embodiment of the invention 2 injections, and 1 time on the one, logotype 3 days; Matched group avilamycin injection, 1 time on the one, logotype 3 days.
Result of the test:
Table 1 liang group curative effect of medication relatively
Evidence, two groups of pig treatment back state of an illness all have clear improvement.Treatment group cure rate and total effective rate are respectively 92.0% and 100%, and matched group is respectively between 60% and 100%, two group cure rate difference extremely significantly (P＜0.01); As seen ivermectin, two kinds of drug regimens of praziquantel and the compound injection made can be widened the anthelmintic spectrum strengthen the ability of animal repelling endoparasite and ectoparasite, and easy to use, drug effect is definite.
Claims (3)
1. compound injection that is used for the animal repelling endoparasite and ectoparasite is characterized in that prescription is made up of Macrolide anthelmintic and praziquantel, wherein the preferred ivermectin of Macrolide anthelmintic.
2. a kind of compound injection that is used for the animal repelling endoparasite and ectoparasite according to claim 1 is characterized in that containing in every injection (5ml/ props up) ivermectin 0.03-0.06g, praziquantel 0.15-0.30g.
3. according to claim 1,2 described a kind of compound injections that are used for the animal repelling endoparasite and ectoparasite, it is characterized in that the preferred ivermectin 0.05g of content, praziquantel 0.25g in every injection (5ml/ props up), subcutaneous injection dosage is 0.1ml/kg.
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 200910069942 CN101987108A (en) | 2009-07-30 | 2009-07-30 | Compound injection for repelling internal and external parasites of animal bodies and preparation method thereof |
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|---|---|---|---|
| CN 200910069942 CN101987108A (en) | 2009-07-30 | 2009-07-30 | Compound injection for repelling internal and external parasites of animal bodies and preparation method thereof |
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102228662A (en) * | 2011-06-15 | 2011-11-02 | 党学云 | Medicament for treating filariasis and preparation method thereof |
| CN103417559A (en) * | 2012-05-15 | 2013-12-04 | 北京中农大动物保健品技术研究院 | Veterinary compound suspension injection containing ivermectin and praziquantel and preparation method thereof |
-
2009
- 2009-07-30 CN CN 200910069942 patent/CN101987108A/en active Pending
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102228662A (en) * | 2011-06-15 | 2011-11-02 | 党学云 | Medicament for treating filariasis and preparation method thereof |
| CN103417559A (en) * | 2012-05-15 | 2013-12-04 | 北京中农大动物保健品技术研究院 | Veterinary compound suspension injection containing ivermectin and praziquantel and preparation method thereof |
| CN103417559B (en) * | 2012-05-15 | 2016-07-13 | 北京中农大动物保健品技术研究院 | Animal compound suspension injection containing ivermectin and praziquantel and preparation method thereof |
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Application publication date: 20110323 |