CN102138890A - Praziquantel transdermal preparation and applications thereof - Google Patents
Praziquantel transdermal preparation and applications thereof Download PDFInfo
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- CN102138890A CN102138890A CN201110081770XA CN201110081770A CN102138890A CN 102138890 A CN102138890 A CN 102138890A CN 201110081770X A CN201110081770X A CN 201110081770XA CN 201110081770 A CN201110081770 A CN 201110081770A CN 102138890 A CN102138890 A CN 102138890A
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Abstract
The invention discloses a praziquantel transdermal preparation prepared from the following components in percentage by weight: 8-35 percent of praziquantel, 40-60 percent of 206 adjuvant and 5-45 percent of aqueous solution or purified water. The invention also discloses applications of the praziquantel transdermal preparation. The praziquantel transdermal preparation provided by the invention not only is convenient to administrate, but also has the same effects on treating and blocking schistosomiasis from being propagated as an oral preparation.
Description
Technical field
The present invention relates to the praziquantel medicine of prevention and cure of schistosomiasis, relate in particular to a kind of praziquantel preparation capable of permeating skin and application thereof.
Background technology
Schistosomiasis endemic is in 76 countries and regions such as the torrid zone and subtropical zones, be a kind of serious infecting both domestic animals and human parasitic disease that endangers, be worldwide distribution, global compromised population is up to 600,000,000 people, number of the infected reaches 200,000,000 people, and the people died from schistosomicide surplus the whole world had 20,000 at least an every year.Before the clinical practice of thoroughly go out on a large scale spiral shell and blood fluke vaccine realized, the anti-schistosomiasis medicine was still the main means of prevention and cure of schistosomiasis.The medicine that is used for the treatment of schistosomicide at present mainly contains praziquantel, artemisinine and derivant such as Artemether etc.In these medicines, praziquantel is few with its curative effect height, short treating period, untoward reaction, but single-dose treatment, and advantage such as easy to use is recommended as the choice drug of treatment schistosomicide by WHO.Present stage, Droncit for animals still is tablet and powder, exists absorption difference, the first pass effect of liver is serious, cause shortcomings such as the low and side effect of utilization ratio of drug is big, and because most domestic animals are ruminant, oral praziquantel destroys the balance of stomach bacterium colony easily.Though occurred at present good absorbing, Praziquantel injection that utilization ratio of drug is high, still there is administration inconvenience in Praziquantel injection, easily brings shortcoming such as pain to domestic animal.
Summary of the invention
The technical problem to be solved in the present invention provides a kind of praziquantel preparation capable of permeating skin, and this preparation capable of permeating skin is convenient drug administration not only, and has the effect of same treatment of oral formulations and blocking-up schistosomiasis propagation.
In addition, also need to provide a kind of application of above-mentioned praziquantel preparation capable of permeating skin.
In order to solve the problems of the technologies described above, the present invention is achieved through the following technical solutions:
In one aspect of the invention, a kind of praziquantel preparation capable of permeating skin is provided, comprise praziquantel, 206 adjuvants and aqueous solution or pure water, its percentage by weight is: praziquantel 8%～35%, 206 adjuvants 40%～60%, aqueous solution or pure water 5%～45%.
Preferably, the percentage by weight of described praziquantel is 20%～30%, because the praziquantel preparation capable of permeating skin therapeutic effect of 20%～30% concentration is good.Preferred, the percentage by weight of described praziquantel is 24%.
Preferably, the percentage by weight of described 206 adjuvants is 50%, i.e. 206 adjuvants/(praziquantel+aqueous solution or pure water)=50/50 (weight ratio) is in the praziquantel preparation capable of permeating skin good stability of this ratio preparation.
The administration time of described praziquantel preparation capable of permeating skin is any a day after the infection schistosomicide.Preferably, the administration time of described praziquantel preparation capable of permeating skin is for infecting the 28th day or any a day after 28 days after the schistosomicide, because used the praziquantel preparation capable of permeating skin in the 28th day or 28 days later on, effect obviously and stable.
Preferably, use the praziquantel preparation capable of permeating skin after the infection schistosomicide during 2-25 days, transdermal 2-3 time, effect is relatively good.
Preferably, for bilharzial ill domestic animal of subinfection or people again, the administration time of praziquantel preparation capable of permeating skin is for infecting 2-25 days after the schistosomicide once more, and promptly the early treatment is effective.
Preferably, it is 0.1～5% transdermal penetrating agent that described praziquantel preparation capable of permeating skin also comprises percentage by weight, and this transdermal penetrating agent is selected from a kind of or two or more combination arbitrarily in the poly-different glycol glyceride of inferior oleoyl, isopropyl myristate, azone, propylene glycol, N-methyl-ketopyrrolidine, oleic acid or the Oleum menthae.Add transdermal penetrating agent in the praziquantel preparation capable of permeating skin, can guarantee that ingredient is easy to transdermal, thereby improve the bioavailability of pharmaceutical preparation with transdermal enhancing effect.
In another aspect of this invention, also provide the preparation method of above-mentioned praziquantel preparation capable of permeating skin, may further comprise the steps:
Respectively an amount of 206 adjuvants, aqueous solution or pure water are heated to 28 ℃～32 ℃;
206 adjuvants and the praziquantel of preheating are mixed, and add the aqueous solution or the further mix homogeneously of pure water of preheating, until obtaining the praziquantel preparation capable of permeating skin.
In another aspect of this invention, also provide the application of above-mentioned praziquantel preparation capable of permeating skin in the medicine of preparation treatment schistosomicide.
In the present invention, term " 206 adjuvant " is meant the adjuvant of Montanide ISA 206 series that France match Bick (SEPPIC) company produces, comprise Montanide ISA 206, ISA 206VG etc., this adjuvant belongs to oil emulsion adjuvant, is W/O/W type (w/o/w) immunological adjuvant that a class contains octadecanoid acid and anhydrous Nitranitol.All in vaccine, use before 206 adjuvants as immunological adjuvant, in order to strengthen the specific immune response of body to antigen vaccine, and 206 adjuvants in the praziquantel preparation capable of permeating skin of the present invention are to use as a kind of medicine solvent, can make fat-soluble medicines such as praziquantel reach higher solubility, have no side effect again, can also give full play to drug effect simultaneously.
Praziquantel preparation capable of permeating skin of the present invention, convenient drug administration not only, and evident in efficacy in prevention and cure of schistosomiasis, safely, have no side effect.
The specific embodiment
The invention provides a kind of praziquantel preparation capable of permeating skin, comprise praziquantel, 206 adjuvants and aqueous solution or pure water, its percentage by weight is: praziquantel 8%～35%, 206 adjuvants 40%～60%, aqueous solution or pure water 5%～45%.
Preferably, the percentage by weight of praziquantel is 20%～30%, and the praziquantel preparation capable of permeating skin therapeutic effect of experiment confirm 20%～30% concentration is good.Preferred, the percentage by weight of praziquantel is 24%.
Preferably, the percentage by weight of 206 adjuvants is 50%, i.e. 206 adjuvants/(praziquantel+aqueous solution or pure water)=50/50 (weight ratio) is in the praziquantel preparation capable of permeating skin good stability of this ratio preparation.
The administration time of praziquantel preparation capable of permeating skin is any a day after the infection schistosomicide.Preferably, the administration time of praziquantel preparation capable of permeating skin is for infecting the 28th day or any a day after 28 days after the schistosomicide, because used the praziquantel preparation capable of permeating skin in the 28th day or 28 days later on, effect obviously and stable.
Preferably, it is 0.1～5% transdermal penetrating agent that the praziquantel preparation capable of permeating skin also comprises percentage by weight, and this transdermal penetrating agent is selected from a kind of or two or more combination arbitrarily in the poly-different glycol glyceride of inferior oleoyl, isopropyl myristate, azone, propylene glycol, N-methyl-ketopyrrolidine, oleic acid or the Oleum menthae.Add transdermal penetrating agent in the praziquantel preparation capable of permeating skin, can guarantee that ingredient is easy to transdermal, thereby improve the bioavailability of pharmaceutical preparation with transdermal enhancing effect.
The preparation method of praziquantel preparation capable of permeating skin of the present invention may further comprise the steps:
Respectively an amount of 206 adjuvants, aqueous solution or pure water are heated to 28 ℃～32 ℃;
206 adjuvants and the praziquantel of preheating are mixed, and add the aqueous solution or the further mix homogeneously of pure water of preheating, until obtaining the praziquantel preparation capable of permeating skin.
Be described in further detail below by embodiment.
Embodiment 1
(1) measures 206 adjuvants of 54ml; Sterilization PBS (PH8.0) 38.32ml of configuration; Above-mentioned solvent is heated to 30 ℃ ± 2 ℃;
(2) take by weighing the 7.68g praziquantel, pour in the aseptic beaker, be preheating to 30 ℃ ± 2 ℃;
(3) 54ml preheating 206 adjuvants of measuring are added in the beaker;
(4) rotary head with FJ-200 high speed dispersion homogenizer is placed in the beaker that praziquantel and 206 adjuvants are housed;
(5) low speed (200-300 rev/min) begins to stir and the 38.32mlPBS of preheating is added gradually, the flow velocity of PBS the 5-10 liter/minute;
(6) accelerate to 2000 rev/mins and kept 10 minutes;
(7) stop to stir and promptly make the praziquantel preparation capable of permeating skin that contains 8% (percentage by weight) praziquantel, wherein the percentage by weight of 206 adjuvants is 50%, percent by volume is 54%; Then the emulsion that makes is placed low temperature (4 ℃～12 ℃).
Embodiment 2
(1) measures 206 adjuvants of 43.2ml; The sterile saline 33.6ml of configuration; Above-mentioned solvent is heated to 30 ℃ ± 2 ℃;
(2) take by weighing the 23.2g praziquantel, pour in the aseptic beaker, be preheating to 30 ℃ ± 2 ℃;
(3) 43.2ml preheating 206 adjuvants of measuring are added in the beaker;
(4) rotary head with FJ-200 high speed dispersion homogenizer is placed in the beaker that praziquantel and 206 adjuvants are housed;
(5) low speed (200-300 rev/min) begins to stir and the 33.6ml normal saline of preheating is added gradually, the flow velocity of normal saline the 5-10 liter/minute;
(6) accelerate to 2000 rev/mins and kept 10 minutes;
(7) stop to stir and promptly make the praziquantel preparation capable of permeating skin that contains 24% (percentage by weight) praziquantel, wherein the percentage by weight of 206 adjuvants is 40%, percent by volume is 43.2%; Then the emulsion that makes is placed low temperature (4 ℃～12 ℃).
Embodiment 3
(1) measures 206 adjuvants of 64.8ml; Measure sterile purified water 5.2ml; Above-mentioned solvent is heated to 30 ℃ ± 2 ℃;
(2) take by weighing the 30g praziquantel, pour in the aseptic beaker, be preheating to 30 ℃ ± 2 ℃;
(3) 64.8ml preheating 206 adjuvants of measuring are added in the beaker;
(4) rotary head with FJ-200 high speed dispersion homogenizer is placed in the beaker that praziquantel and 206 adjuvants are housed;
(5) low speed (200-300 rev/min) begins to stir and the 5.2ml pure water of preheating is added gradually, the flow velocity of pure water the 5-10 liter/minute;
(6) accelerate to 2000 rev/mins and kept 10 minutes;
(7) stop to stir and promptly make the praziquantel preparation capable of permeating skin that contains 31.5% (percentage by weight) praziquantel, wherein the percentage by weight of 206 adjuvants is 60%, percent by volume is 64.8%; Then the emulsion that makes is placed low temperature (4 ℃～12 ℃).
Embodiment 4
(1) measures 206 adjuvants of 43.2ml; Sterilization PBS (PH8.0) 22.92ml of configuration; Above-mentioned solvent is heated to 30 ℃ ± 2 ℃;
(2) take by weighing the 33.88g praziquantel, pour in the aseptic beaker, be preheating to 30 ℃ ± 2 ℃;
(3) 43.2ml preheating 206 adjuvants of measuring are added in the beaker;
(4) rotary head with FJ-200 high speed dispersion homogenizer is placed in the beaker that praziquantel and 206 adjuvants are housed;
(5) low speed (200-300 rev/min) begins to stir and the 22.92mlPBS of preheating is added gradually, the flow velocity of PBS the 5-10 liter/minute;
(6) accelerate to 2000 rev/mins and kept 10 minutes;
(7) stop to stir and promptly make the praziquantel preparation capable of permeating skin that contains 35% (percentage by weight) praziquantel, wherein the percentage by weight of 206 adjuvants is 40%, percent by volume is 43.2%; Then the emulsion that makes is placed low temperature (4 ℃～12 ℃).
Embodiment 5 praziquantel preparation capable of permeating skin are to the treatment of the new zealand white rabbit of infection Schistosoma japonicum
1. method
1.1 grouping scheme
For the effect of different times skin-penetrating therapeutic behind the praziquantel preparation capable of permeating skin of investigating variable concentrations, different transdermal number of times and single infection and the superinfection, establish independent experiment twice, matched group is all established in each experiment.Every group of 3-4 only tests and uses new zealand white rabbit.Experiment one, the therapeutic effect of investigation variable concentrations praziquantel preparation capable of permeating skin, different transdermal number of times, 28d carries out skin-penetrating therapeutic behind the single infection, establishes treatment group A1: transdermal agent concentration 24%, transdermal 1 time; Treatment group B1: transdermal agent concentration 24%, transdermal is 2 times continuously.Experiment two, investigate 24% transdermal agent concentration to schistosomicide single infection and the early stage skin-penetrating therapeutic effect of superinfection, wherein the superinfection group is it to be treated in the 28th day behind single infection, and carried out superinfection in back 45 days in infection, each organizes equal transdermal 2 times, establishes treatment group A2: treatment in 1 day behind the superinfection; Treatment group B2: treatment in 7 days behind the superinfection; Treatment group C2: treatment in 14 days behind the superinfection; Treatment group D: 1 day skin-penetrating therapeutic behind the single infection; Treatment group E: 14 days skin-penetrating therapeutics behind the single infection.
1.2. artificial challenge's schistosomicide
Experimental rabbit is fixed on the plank, takes out the abdominal part rabbit hair, anatomical lens is counted cercaria down, tests 150 ± 2 cercarias of every quantitative infection, tests two every quantitative 300 ± 2 cercarias, slide subsides abdomens 20 minutes of infecting.
1.3 skin-penetrating therapeutic
The body weight of weighing experimental rabbit is carried out skin-penetrating therapeutic by 100mg/kg dosage, and experimental rabbit is fixed on the plank, removes the abdominal part rabbit hair, smears the praziquantel preparation capable of permeating skin, and each transdermal area is 4cm
2, the transdermal time is 30 minutes.After transdermal finished, the wiping abdominal part was directly put back to rabbit in the cage, and normal the raising every 24 hours, observed situations such as transdermal place's skin and experimental rabbit feed.
1.4 the insecticidal effect of transdermal agent
Adult is seized: dissected in 45-46 days respectively at infecting the back, go out polypide counting in portal vein-mesenteric vein regulating liver-QI with the heart perfusion, be calculated as follows worm reduction rate:
A is average every the one-tenth borer population that rabbit is seized of matched group in the formula, and b is average every the one-tenth borer population that rabbit is seized of treatment group.
1.5 the liver ovum rate that subtracts of transdermal agent
Liver egg count: get every about 2-4 gram of experimental rabbit same area liver, be settled to 20mL after weighing, the homogenate of homogenizing instrument, get 2mL liver homogenate liquid and add 45 ℃ of digestion of 2mLNaOH (10mol/L) 30-60min, get counting under the 100 μ L optical microscopes then, every sample counting three times, and converse gram liver worm's ovum number (Egg per gram of liver, EPG).Be calculated as follows the liver ovum rate that subtracts:
M is the worm's ovum number that the average every gram liver of matched group comprises in the formula, and n is that the worm's ovum number that average every gram liver comprises is organized in treatment.
1.6 suppress worm's ovum miracidium incubation rate
Get enteral feces 5-10 gram or same area liver 2-4 gram after experimental rabbit is dissected respectively, be settled to 20ml after weighing, the homogenate of homogenizing instrument.Hatching house and hatching coolant-temperature gage remain on about 25 ℃, add the feces of homogenate or 4ml liver homogenate liquid in 500ml long-neck boiling flask, add hatching water to bottleneck with absorbent cotton, on cotton layer, add 8ml dechlorination water, the constant temperature hatching.For the liver hatching, sampling method is as follows, 1h and 3h sampling after hatching respectively, 1h draws the water 8ml that contains miracidium on the cotton layer with suction pipe, move in the centrifuge tube, the dechlorination water that adds the 8ml water temperature again be in hatching bottle about 25 ℃ continues hatching, uses in order to sampling for the second time.In containing the artemia hatching solution of miracidium, add that Formalin is fixed, the centrifugal 10min of 8000rpm, remove supernatant in 5% ratio, precipitation adds iodine tincture 1-2 and drips painted, draw in the centrifuge tube all liquid on microscope slide with suction pipe, count the miracidium number under the anatomical lens respectively, and converse gram liver hatching miracidium number, be calculated as follows and subtract the miracidium incubation rate:
X is the miracidium number that the average every gram liver of matched group comprises in the formula, and y is that the miracidium number that average every gram liver comprises is organized in treatment.For stool for hatching, whether 1h and 3h observe the absorbent cotton upper strata after hatching miracidium, and 1h has miracidium record "+", no miracidium record "-" when observing.3h observes miracidium and increases record "+", does not see and increases record "-".Final result only writes down total "+", does not all observe miracidium meter record "-" 2 times.
1.7 statistical analysis
Test data carries out statistical analysis with SPSS software, calculates the arithmetical average and the standard deviation of each index
Simultaneously, whether the difference of calculating between the contrast groups has statistical significance.
2. result
2.1 the zest of preparation capable of permeating skin is observed
Experimental rabbit does not have tangible mental status abnormality after the treatment of praziquantel preparation capable of permeating skin, observed continuously 2 days, and each appetite is normal, does not find that symptoms such as redness, inflammation appear in transdermal position skin, and the medication that transdermal agent is described is safe.
2.2 preparation capable of permeating skin is to the effect of imago of blood fluke
When 28d treated after infection, each treatment group all had therapeutic effect, illustrated that preparation capable of permeating skin has good killing effect to adult.As shown in table 1, observing clearly, skin-penetrating therapeutic respectively organize worm reduction rate all more than 80%, subtract liver ovum rate also all more than 50%, wherein B1 group concentration is that 24% preparation capable of permeating skin subtracts liver ovum rate up to 100%, see through the stool for hatching situation of observing, also the faecal egg of each group is all turned out cloudy as can be seen.But therapeutic effect has certain difference, and B1 that transdermal is 2 times group is better than the A1 group therapeutic effect of transdermal 1 time.
The therapeutic effect of table 1 single infection different praziquantel preparation capable of permeating skin concentration and different transdermal number of times after 28 days
A: compare with the concurrent control group, difference all has statistical significance (P＜0.05); B: compare with the concurrent control group, difference all has statistical significance (P＜0.01).
2.3 preparation capable of permeating skin is to the effect of schistosomulum
By table 2 data show, to the D group worm reduction rate that infects the 1st day skin-penetrating therapeutic in back with subtract liver ovum rate and be respectively 61.30% and 92.27%, all apparently higher than the E group of treatment in the 14th day.Two groups the miracidium incubation rate that subtracts does not have too big-difference.The data of B1 group adopt identical preparation capable of permeating skin concentration and transdermal number of times as can be seen in the associative list 1, at metainfective the 1st day, the 14th day and the 28th day it are carried out skin-penetrating therapeutic, and are wherein best to infect the 28th day therapeutic effect in back.The effect and the oral medication effect that infected the back the 1st day and treated in the 14th day are consistent, and illustrate that the praziquantel preparation capable of permeating skin is to the too late adult of the killing action of virgin worm.
Table 2 single infection and infect the therapeutic effect of early stage (1d, 7d, 14d) praziquantel preparation capable of permeating skin again
A: compare with the concurrent control group, difference all has statistical significance (P＜0.05).
2.4 preparation capable of permeating skin is to infecting the effect of schistosomulum again
Select the 28th day skin-penetrating therapeutic experimental rabbit in infection back to carry out schistosomicide and infect again, carry out skin-penetrating therapeutic, can see that by table 2 the praziquantel preparation capable of permeating skin has different killing actions to the virgin worm of single infection and infection again respectively at metainfective 1d, 7d and 14d.Infect the 1st day skin-penetrating therapeutic in back, infect the A2 group again, be respectively 86.80% and 61.30% than single infection D group worm reduction rate height.Infect back treatment in the 14th day, the C2 group is also higher than single infection E group worm reduction rate infecting.Illustrate that the praziquantel preparation capable of permeating skin has different killing actions to infecting virgin worm again with the virgin worm of single infection.
The above embodiment has only expressed embodiments of the present invention, and it describes comparatively concrete and detailed, but can not therefore be interpreted as the restriction to claim of the present invention.Should be pointed out that for the person of ordinary skill of the art without departing from the inventive concept of the premise, can also make some distortion and improvement, these all belong to protection scope of the present invention.Therefore, the protection domain of patent of the present invention should be as the criterion with claims.
Claims (9)
1. a praziquantel preparation capable of permeating skin is characterized in that, comprises praziquantel, 206 adjuvants and aqueous solution or pure water, and its percentage by weight is: praziquantel 8%～35%, 206 adjuvants 40%～60%, aqueous solution or pure water 5%～45%.
2. praziquantel preparation capable of permeating skin according to claim 1 is characterized in that, the percentage by weight of described praziquantel is 20%～30%.
3. praziquantel preparation capable of permeating skin according to claim 2 is characterized in that, the percentage by weight of described praziquantel is 24%.
4. according to each described praziquantel preparation capable of permeating skin in the claim 1 to 3, it is characterized in that the percentage by weight of described 206 adjuvants is 50%.
5. according to each described praziquantel preparation capable of permeating skin in the claim 1 to 3, it is characterized in that the administration time of described praziquantel preparation capable of permeating skin is any a day after the infection schistosomicide.
6. praziquantel preparation capable of permeating skin according to claim 5 is characterized in that, the administration time of described praziquantel preparation capable of permeating skin is the 28th day or any a day after 28 days after the infection schistosomicide.
7. praziquantel preparation capable of permeating skin according to claim 1, it is characterized in that, also comprise percentage by weight and be 0.1～5% transdermal penetrating agent, this transdermal penetrating agent is selected from a kind of or two or more combination arbitrarily in the poly-different glycol glyceride of inferior oleoyl, isopropyl myristate, azone, propylene glycol, N-methyl-ketopyrrolidine, oleic acid or the Oleum menthae.
8. the preparation method of the described praziquantel preparation capable of permeating skin of claim 1 is characterized in that, may further comprise the steps:
Respectively an amount of 206 adjuvants, aqueous solution or pure water are heated to 28 ℃～32 ℃;
206 adjuvants and the praziquantel of preheating are mixed, and add the aqueous solution or the further mix homogeneously of pure water of preheating, until obtaining the praziquantel preparation capable of permeating skin.
9. the application of the described praziquantel preparation capable of permeating skin of claim 1 in the medicine of preparation treatment schistosomicide.
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102860981A (en) * | 2012-10-26 | 2013-01-09 | 天津必佳药业集团有限公司 | Schistosomiasis resistant praziquantel transdermal solution for flocks and herds and preparation method |
| CN109674739A (en) * | 2019-01-25 | 2019-04-26 | 西藏农牧学院 | A kind of transdermal liniment and preparation method thereof for preventing and treating Yak parasitoses |
| CN111991411A (en) * | 2020-09-28 | 2020-11-27 | 吉林吉力生物技术研究有限公司 | Application of composition in preparation of veterinary anthelmintic drug, transdermal anthelmintic solution for veterinary use and preparation method of transdermal anthelmintic solution |
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| CN101623500A (en) * | 2009-07-28 | 2010-01-13 | 中国农业科学院上海兽医研究所 | Application of oil emulsion adjuvant |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN101623500A (en) * | 2009-07-28 | 2010-01-13 | 中国农业科学院上海兽医研究所 | Application of oil emulsion adjuvant |
Non-Patent Citations (1)
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| 《湖北预防医学杂志》 19901231 湖北省吸血虫病防治研究所 "吡喹酮经皮肤途径给药治疗家兔血吸虫病的实验报告" 第52页及第40页 1－9 第1卷, 第1期 * |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102860981A (en) * | 2012-10-26 | 2013-01-09 | 天津必佳药业集团有限公司 | Schistosomiasis resistant praziquantel transdermal solution for flocks and herds and preparation method |
| CN109674739A (en) * | 2019-01-25 | 2019-04-26 | 西藏农牧学院 | A kind of transdermal liniment and preparation method thereof for preventing and treating Yak parasitoses |
| CN111991411A (en) * | 2020-09-28 | 2020-11-27 | 吉林吉力生物技术研究有限公司 | Application of composition in preparation of veterinary anthelmintic drug, transdermal anthelmintic solution for veterinary use and preparation method of transdermal anthelmintic solution |
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