CN107693532A - Compound anti-parasitic preparation and preparation method thereof - Google Patents
Compound anti-parasitic preparation and preparation method thereof Download PDFInfo
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- CN107693532A CN107693532A CN201711046888.2A CN201711046888A CN107693532A CN 107693532 A CN107693532 A CN 107693532A CN 201711046888 A CN201711046888 A CN 201711046888A CN 107693532 A CN107693532 A CN 107693532A
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- 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
- A61K31/7042—Compounds having saccharide radicals and heterocyclic rings
- A61K31/7048—Compounds having saccharide radicals and heterocyclic rings having oxygen as a ring hetero atom, e.g. leucoglucosan, hesperidin, erythromycin, nystatin, digitoxin or digoxin
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- 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
- A61K31/4164—1,3-Diazoles
- A61K31/4184—1,3-Diazoles condensed with carbocyclic rings, e.g. benzimidazoles
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- 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
- A61K31/53—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with three nitrogens as the only ring hetero atoms, e.g. chlorazanil, melamine
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- 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
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2013—Organic compounds, e.g. phospholipids, fats
- A61K9/2018—Sugars, or sugar alcohols, e.g. lactose, mannitol; Derivatives thereof, e.g. polysorbates
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- 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
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2022—Organic macromolecular compounds
- A61K9/205—Polysaccharides, e.g. alginate, gums; Cyclodextrin
- A61K9/2054—Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
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- 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
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2022—Organic macromolecular compounds
- A61K9/205—Polysaccharides, e.g. alginate, gums; Cyclodextrin
- A61K9/2059—Starch, including chemically or physically modified derivatives; Amylose; Amylopectin; Dextrin
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Abstract
The present invention relates to a kind of compound anti-parasitic preparation and its preparation method and application.The compound anti-parasitic preparation is mainly prepared by each raw material of following parts by weight：1 part of 0.1 part of ivermectin 0.04 part, 10 parts of mebendazole 5 part, 15 parts of toltrazuril 5 part, 10 parts of disintegrant 3 part, 91 parts of filler 61 part, 3 parts of lubricant 1 part and adhesive 0.3 part.The uniformity of the compound anti-parasitic preparation is high and with preferably anti parasitic effect.
Description
Technical field
The present invention relates to anti-parasite medicine technical field, more particularly to a kind of compound anti-parasitic preparation and its system
Preparation Method.
Background technology
With the raising of economic capability, increasing people raises dog, cat etc. and is used as pet.As canine can not only give
The flat life of people increases enjoyment, and can alleviate the lonely and pressure of people's heart.But Canis moves in mammality
Thing, the parasitic diseases such as nematode, tapeworm, coccidia are susceptible to suffer from, if can not get timely medical treatment, not only influence the health of canine, can also increase
Add the risk of human infection's parasitic disease.Further, since canine and other mammals are also easily handed in daily life
Bacteria infection parasite is pitched, and can mutually be infected between different germ parasites, so as to which the illness of Different types of etiopathogenises can be suffered from.
Ivermectin is new less toxic antibioticses antiparasitic agent, and the effect killed is respectively provided with to internal ectoparasite.
But traditional ivermectin tablet is single preparations of ephedrine, pest-resistant spectrum is narrower, it is difficult to effective complete treatment nematode, tapeworm, coccidia
It is poor etc. parasitic disease, the therapeutic effect of the especially illness to mutually being infected between different parasites.
The content of the invention
Based on this, it is necessary to which providing one kind, can effectively to prevent and treat nematode, tapeworm, coccidia and the uniformity comprehensively preferably multiple
Square antiparasitic formulations and preparation method thereof.
A kind of compound anti-parasitic preparation, mainly it is prepared by each raw material of following parts by weight：Ivermectin 0.04
- 0.1 part of part, 5 parts -10 parts of mebendazole, 5 parts -15 parts of toltrazuril, 3 parts -10 parts of disintegrant, 61 parts -91 parts of filler, profit
0.3 part -1 part of 1 part -3 parts of lubrication prescription and adhesive.
In one of the embodiments, in addition to flavor enhancement that parts by weight are 1 part -4 parts and 0.01 part -0.04 part
Preservative.
In one of the embodiments, it is prepared by each raw material of following parts by weight：0.05 part -0.1 of ivermectin
Part, 7 parts -9 parts of mebendazole, 8 parts -12 parts of toltrazuril, 5 parts -8 parts of disintegrant, 61 parts -71 parts of filler, 1 part of lubricant -
0.01 part -0.03 part of 2 parts, 0.5 part -0.8 part of adhesive, 1 part -2 parts of flavor enhancement and preservative.
In one of the embodiments, the disintegrant is sodium carboxymethyl starch, PVPP, cross-linked carboxymethyl fibre
Tie up the one or more in plain sodium, ethyl cellulose, methylcellulose, lauryl sodium sulfate and polyvinylpyrrolidone.
In one of the embodiments, the filler be anhydrous Icing Sugar, lactose, sucrose, starch, microcrystalline cellulose and
One or more in maltodextrin.
In one of the embodiments, the filler is lactose, microcrystalline cellulose and maltodextrin, wherein, the breast
The mass ratio of sugared, described microcrystalline cellulose and the maltodextrin is (50-80)：(5-10)： (4-8).
In one of the embodiments, the lactose, the mass ratio of the microcrystalline cellulose and the maltodextrin are
52：10：5.
In one of the embodiments, the flavor enhancement is beef flavor and/or chicken essence；The lubricant is hard
One or more in fatty acid magnesium, talcum powder and superfine silica gel powder；Described adhesive is sodium carboxymethylcellulose, starch slurry, hydroxypropyl
One or more in methylcellulose or PVP；The preservative be parabens, butylated hydroxy anisole or
One or more in dibutyl hydroxy toluene.
Compound anti-parasitic preparation in the present invention is the sheet system being processed into by main ingredient and suitable excipient substance
Agent.Count in parts by weight, the main ingredient includes 0.04 part -0.1 part of ivermectin, 5 parts -10 parts of mebendazole and toltrazuril 5
- 15 parts of part, the excipient substance includes 3 parts -10 parts of disintegrant, 61 parts -91 parts of filler, 1 part -3 parts of lubricant and adhesive
0.3 part -1 part.The compound anti-parasitic preparation is by ivermectin, mebendazole and the united compound of toltrazuril multiple medicine
Preparation, not only pest-resistant spectrum is more extensive, and produces preferably collaboration wide spectrum expelling parasite insecticidal effect, can effectively kill nematode, silk ribbon
The parasites such as worm, coccidia.The compound anti-parasitic preparation by control ivermectin, mebendazole, toltrazuril, disintegrant,
The ratio of filler, lubricant and adhesive, it is ensured that ivermectin, mebendazole, toltrazuril can be equably
It is dispersed in each excipient substance, the compound anti-parasitic preparation of the uniformity preferably can be made, and with preferably using effect
Fruit and security performance.
In addition, the filler in the present invention uses lactose, microcrystalline cellulose and maltodextrin, and by controlling lactose, micro-
The mass ratio of crystalline cellulose and maltodextrin is (50-80)：(5-10)：(1-10), its filler being collectively forming have suitable
Suitable caking property and mobility, it is ensured that ivermectin, mebendazole and toltrazuril can be dispersed, and then prepare shape
Into compound anti-parasitic preparation the uniformity it is preferable.In addition, the filler that lactose, microcrystalline cellulose and maltodextrin are formed
Hardness it is suitable, it is preferable to prepare the dissolving out capability of main ingredient in the compound anti-parasitic preparation of formation, and then the compound anti-parasitic
The using effect and security performance of preparation are all preferable.
The disintegrant of the present invention is fine from sodium carboxymethyl starch, PVPP, Ac-Di-Sol, ethyl
When tieing up the one or more in element, methylcellulose, lauryl sodium sulfate and polyvinylpyrrolidone, its disintegration effect compared with
It is good, the dissolution of ivermectin is helped lend some impetus to, and then further increase the using effect and safety of compound anti-parasitic preparation
Performance.When disintegrant is PVPP, it can make disintegration of tablet rapid, not only be easier to soak medicaments uniformity, and
Hydrophobic drug surface can be made to be changed into hydrophily, further promote the dissolution of medicine and the disintegration of tablet.
A kind of preparation method of compound anti-parasitic preparation is provided in addition, there is a need to.
A kind of preparation method of compound anti-parasitic preparation, comprises the following steps：
By parts by weight described above weigh respectively ivermectin, mebendazole, toltrazuril, disintegrant, filler,
Lubricant and adhesive；
Each raw material weighed is subjected to pulverization process respectively, and handled by the mesh sieve of 60 mesh -120；
The ivermectin after sieving is added in absolute ethyl alcohol and is completely dissolved, the institute added after the sieving of part
State filler to be well mixed, drying, crushing and sieving processing, ivermectin solid dispersion body is made, wherein, the Yi Wei
The content of ivermectin described in rhzomorph solid dispersions is 1%-5%；
Described adhesive after sieving is added in solvent, it is 0.1% (w/v) -10% (w/v) that preparation, which obtains concentration,
Binder solution；
By the mebendazole after sieving, the toltrazuril after sieving, the disintegrant after sieving, residue
Sieving after the filler and the ivermectin solid dispersion body be well mixed by the equivalent method of progressively increasing, and add
Described adhesive solution, softwood is made；
The softwood is pelletized, dry and whole grain, particle is made, wherein, the water content of the particle is 2%-
7%；
The lubricant after sieving is well mixed with the particle, through compressing tablet process, produces compound anti-parasitic system
Agent, wherein, the hardness of the compound anti-parasitic preparation is 1kgf-7kgf.
In one of the embodiments, the mass ratio of the ivermectin and the absolute ethyl alcohol is 1： (20-40).
The preparation method of heretofore described compound anti-parasitic preparation, can significantly improve compound anti-parasitic system
The uniformity and dissolution rate of agent, effectively improve the effectiveness and reliability of medicine.In compound anti-parasitic of the present invention
In the preparation method of preparation, by ivermectin, mebendazole, toltrazuril, disintegrant, filler, lubricant and adhesive
Handled after crushing respectively with the mesh sieve of 60 mesh -120, to ensure that the particle diameter of each raw material is smaller and uniform, it is ensured that Yi Wei after mixing
The content of rhzomorph, mebendazole and toltrazuril is uniform, fine and smooth uniform compound anti-parasitic preparation can be made, it has
The dissolution rate for imitating composition is accelerated.In addition, the particle diameter of ivermectin, mebendazole, toltrazuril is relatively small, surface area compared with
Greatly, its solubility property is preferable.
By the way that the ivermectin after sieving is added in absolute ethyl alcohol, ivermectin can be carried out in absolute ethyl alcohol
Fully dissolving, then be well mixed with the filler after the sieving of part, drying, crushing and sieving processing, Yi Wei bacterium are made
Plain solid dispersions.Ivermectin can be dispersed in the ivermectin solid dispersion body, and it is mixed with each raw material to expand it
It splice grafting contacting surface, can uniformly be distributed in auxiliary material, effectively increase the uniformity of compound anti-parasitic preparation.By using
The equivalent method of progressively increasing is well mixed mebendazole, toltrazuril, filler and ivermectin solid dispersion body, further has
Effect improves the uniformity of compound anti-parasitic preparation.
By controlling the concentration of binder solution it is 0.1% (w/v) -10% (w/v) in the present invention, it is ensured that Compound Resisting is posted
Infested preparation has suitable viscosity, can reduce the contact angle of compound anti-parasitic preparation, makes it easier to soak, effectively changes
The secondary disintegration of kind compound anti-parasitic preparation, so as to significantly improve the dissolution rate of compound anti-parasitic preparation.
It is 1%- by controlling the water content of particle in heretofore described compound anti-parasitic formulation preparation method
5%.The particle has the preferable uniformity and mobility, and ivermectin content distribution is uniform, and then effectively increases Compound Resisting
The uniformity of parasite preparations.
In heretofore described compound anti-parasitic formulation preparation method, by controlling compound anti-parasitic preparation
Hardness is 1kgf-7kgf, it is ensured that compound anti-parasitic preparation has preferable specific surface area, porosity and duct rate, can
The disintegration efficiency of compound anti-parasitic preparation is effectively improved, and then with dissolving out capability preferably.
In heretofore described compound anti-parasitic formulation preparation method, by control ivermectin with it is described anhydrous
The mass ratio of ethanol is 1：(20-40), it is ensured that absolute ethyl alcohol can preferably dissolve ivermectin, and then ensure ivermectin
More uniform to be dispersed in auxiliary material, obtained compound anti-parasitic preparation has a preferable uniformity, so the performance of medicine compared with
It is good.
Therefore, the uniformity of compound anti-parasitic preparation produced by the present invention and dissolution rate are preferable, and then effectively increase
The effectiveness and reliability of medicine.
Compound anti-parasitic preparation in the present invention can be used for outer expelling parasite inside the animals such as canine.Such as Compound Resisting
Parasite preparations are chewable tablets, and animal carries out internal expelling parasite by being swallowed after the compound anti-parasitic preparation is chewed.This is multiple
The using effect and security performance of square antiparasitic formulations are all preferable.
Embodiment
For the ease of understanding the present invention, the present invention is described more fully below in conjunction with embodiment.But this
Invention can be realized in many different forms, however it is not limited to embodiment described herein.On the contrary, provide these realities
The purpose for applying example is to make the understanding more thorough and comprehensive to the disclosure.
Unless otherwise defined, technical field of all of technologies and scientific terms used here by the article with belonging to the present invention
The implication that is generally understood that of technical staff it is identical.Term used in the description of the invention herein is intended merely to retouch
State the purpose of specific embodiment, it is not intended that in the limitation present invention.Term as used herein "and/or" include one or
The arbitrary and all combination of multiple related Listed Items.
The test method of unreceipted actual conditions in the following example, conventionally and condition, or said according to commodity
The condition of bright book suggestion is selected.Agents useful for same or the unreceipted production firm person of instrument, it is that can be obtained by commercially available purchase
Conventional products.
The compound anti-parasitic preparation is to pass through the Formulation being processed into by main ingredient and suitable auxiliary material.The compound
Antiparasitic formulations are mainly prepared by each raw material of following parts by weight：0.04 part -0.1 part of ivermectin, such as can be with
For, but it is not limited to 0.04 part, 0.05 part, 0.06 part, 0.08 or 0.1 part；5 parts -10 parts of mebendazole, such as can be, but not
Be limited to 5 parts, 6 parts, 7 parts, 8 parts or 10 parts, 5 parts -15 parts of toltrazuril, such as can be, but be not limited to 5 parts, 6 parts, 8 parts, 10
Part, 12 parts or 15 parts, 3 parts -10 parts of disintegrant, such as can be, but be not limited to 3 parts, 4 parts, 5 parts, 6 parts, 7 parts, 8 parts or 10
Part；61 parts -91 parts of filler, such as can be, but it is not limited to 61 parts, 70 parts, 75 parts, 80 parts, 83.76 parts, 85 parts or 91
Part；1 part -3 parts of lubricant, such as can be, but it is not limited to 1 part, 2 parts or 3 parts；0.3 part -1 part of adhesive, such as can be with
For, but it is not limited to 0.3 part, 0.5 part, 0.6 part, 0.7 part, 0.8 part, 0.9 part or 1 part.
In one embodiment, 1 part -4 parts of flavor enhancement, such as can be, but it is not limited to 1 part, 2 parts, 3 parts or 4 parts；It is anti-
Rotten 0.01 part -0.04 part of agent, such as can be, but it is not limited to 0.01 part, 0.02 part, 0.03 part or 0.04 part.
In one embodiment, the compound anti-parasitic preparation is mainly prepared by each raw material of following parts by weight
0.05 part -0.1 part of ivermectin, 7 parts -9 parts of mebendazole, 8 parts -12 parts of toltrazuril, 5 parts -8 parts of disintegrant, filler 61
0.01 part -0.03 of parts -71 parts, 1 part -2 parts of lubricant, 0.5 part -0.8 part of adhesive, 1 part -2 parts of flavor enhancement and preservative
Part.
In one embodiment, it is prepared by each raw material of following parts by weight：0.08 part of ivermectin, toluene miaow
8 parts of azoles, 10 parts of toltrazuril, 7 parts of disintegrant, 67.2 parts of filler, 1 part of flavor enhancement, 1 part of lubricant, 0.7 part of adhesive with
And 0.02 part of preservative.
The disintegrant refers to the material that tablet can be made to split into fine particle rapidly in gastro-intestinal Fluid so that main ingredient into
Divide rapid solution absorption, play a role.The disintegrant needs have good water imbibition and dilatancy, so as to realize tablet
Disintegration.Alternatively, the disintegrant be sodium carboxymethyl starch, PVPP, Ac-Di-Sol, ethyl cellulose,
One or more in methylcellulose, lauryl sodium sulfate and polyvinylpyrrolidone etc., its disintegration effect is preferable, has
Help promote the dissolution of ivermectin, and then further increase the using effect and security performance of compound anti-parasitic preparation.
Still optionally further, the disintegrant is PVPP, and it can make disintegration of tablet rapid, not only be easier to moisten medicaments uniformity
It is wet, and hydrophobic drug surface can be made to be changed into hydrophily, further promote the dissolution of medicine and the disintegration of tablet.
The weight or volume for being mainly used in filling tablet of the filler, so as to dilute main ingredient, being easy to, which increases volume, helps it
Shaping.Alternatively, the filler be lactose, anhydrous Icing Sugar, sucrose, starch, microcrystalline cellulose, maltodextrin, inorganic salts and
One or more in amylum pregelatinisatum etc..Wherein, sucrose refers to the white that crystallinity sucrose forms after low temperature drying crushes
Powder, its bonding force are strong, by increasing capacitance it is possible to increase the hardness of tablet, and make the surface smooth and beautiful appearance of tablet.The compressibility energy of anhydrous Icing Sugar
Good, property is stable, and chemically reactive, the tablet being pressed into be not bright and clean attractive in appearance with most drug.The property of starch is stable, and big
Most medicines do not work, and price is also relatively cheap, and hygroscopicity is small, appearance luster is good.Microcrystalline cellulose is cellulosic sections water
Prepared by solution the less crystallinity cellulose of the degree of polymerization, there is good compressibility, have stronger adhesion, the piece being pressed into
Agent has and larger has hardness.Amylum pregelatinisatum has good mobility, compressibility, self-lubricity and dry adhesive.Dextrin is
The general name of Starch Hydrolysis intermediate product, maltodextrin form using starch as raw material through enzyme method technique control hydrolysis.
In one embodiment, the filler is lactose, microcrystalline cellulose and maltodextrin, wherein, the lactose, this is micro-
Crystalline cellulose and the mass ratio of the maltodextrin are (50-80)：(5-10)：(1-10).Alternatively, the lactose, the crystallite are fine
The mass ratio of dimension element and the maltodextrin is 52：10：5.The filler that lactose, microcrystalline cellulose and malt paste are collectively forming
With suitable caking property and mobility, it is ensured that each main ingredient can be dispersed, and then prepares the compound anti-parasitic system formed
The uniformity of agent is preferable.In addition, the hardness for the filler that lactose, microcrystalline cellulose and maltodextrin are formed is suitable, prepares and formed
Compound anti-parasitic preparation of traditional Chinese medicine dissolving out capability it is preferable, and then the compound anti-parasitic preparation using effect and safety
Performance is all preferable.
The flavor enhancement is used for the organoleptic properties for improving food, makes food tastier, and can promote point of digestive juice
Secrete and orectic food additives.Alternatively, the flavor enhancement is beef flavor, chicken essence, dog taste flavouring agent, milk powder
Or the one or more in chicken liver meal etc..
The lubricant is used to reduce frictional force between particle, improves powder flowbility, prevents auxiliary material from sticking at punch head surface,
Reduce the frictional force between tablet and punch die hole wall.Alternatively, the lubricant is in magnesium stearate, talcum powder and superfine silica gel powder etc.
One or more.
The adhesive is the sticking material of tool, and drug material can link together by its viscosity.Alternatively, should
Adhesive is in sodium carboxymethylcellulose, starch slurry, hydroxypropyl methylcellulose, methylcellulose or ethyl cellulose, PVP etc.
One or more.During using adhesive, it can be added into or be scattered in water, in ethanol equal solvent, to be configured to required concentration
Binder solution.Alternatively, the concentration of binder solution is 0.6% (w/v) -10% (w/v).If starch slurry is in tablet
More common adhesive, the concentration of its starch slurry solution matched somebody with somebody are generally 2% (w/v) -10% (w/v)；When material compressibility
Can be poor, the starch slurry using higher concentration may be selected；If material compressibility can be good, the starch slurry of low concentration may be selected.If adopt
During by the use of sodium carboxymethylcellulose as adhesive, the concentration of its sodium carboxymethyl cellulose solution prepared is generally 0.1%
(w/v) -4% (w/v).During according to hydroxypropyl methylcellulose as adhesive, its prepare the hydroxypropyl methylcellulose aqueous solution it is dense
Degree is generally 1% (w/v) -6% (w/v).During according to PVP as adhesive, its prepare the PVP aqueous solution it is dense
Degree is generally 2% (w/v) -5% (w/v).
The preservative is used to keep the drug effect on medicine ground and using quality.Alternatively, the preservative is P-hydroxybenzoic acid
One or more in esters, butylated hydroxy anisole or dibutyl hydroxy toluene etc..
The absolute ethyl alcohol is used to dissolve ivermectin.The ivermectin can carry out preferably scattered in absolute ethyl alcohol.Its
In, by the dosage for adjusting absolute ethyl alcohol, it is ensured that ivermectin can be completely dissolved.Alternatively, the dosage of the absolute ethyl alcohol is
20 times -40 times of ivermectin dosage.When absolute ethyl alcohol can be completely dissolved ivermectin, the ivermectin can be uniform
Ground is mixed with auxiliary material, and the uniformity of the compound anti-parasitic preparation of formation is preferable.
Ivermectin is novel low-toxicity antibioticses antiparasitic agent, and good kill is respectively provided with to internal ectoparasite
Effect, it is preferable especially for the repelling and killing efficacy of nematode and arthropod.Mebendazole can suppress nematode and glucose is taken the photograph
Enter, consume its glycogen depletion, and then it is killed.Mebendazole can be used in prevent and treat hookworm, roundworm, pinworm, whipworm,
The Enterozoa such as strongyloides intestinalis and tapeworm individually or mixed infection.Toltrazuril kills effect to coccidia with good,
It can interfere with the mitochondria of coccidia and nuclear division, influence breathing and the metabolic function of polypide, and and can makes into the cell in addition
Matter net expands, and serious ghost occurs, it is thus possible to preferably kill coccidia.
Compound anti-parasitic preparation in the present invention is the sheet system being processed into by main ingredient and suitable excipient substance
Agent.Count in parts by weight, the main ingredient includes 0.04 part -1 part of ivermectin, 5 parts -10 parts of mebendazole and toltrazuril 5
- 15 parts of part, the excipient substance includes 3 parts -10 parts of disintegrant, 61 parts -91 parts of filler, 1 part -3 parts of lubricant and adhesive
0.3 part -1 part.The compound anti-parasitic preparation is by ivermectin, mebendazole and the united compound of toltrazuril multiple medicine
Preparation, not only pest-resistant spectrum is more extensive, and produces preferably collaboration wide spectrum expelling parasite insecticidal effect, can effectively kill dog nematode, silk ribbon
The parasites such as worm, coccidia.The compound anti-parasitic preparation by control ivermectin, mebendazole, toltrazuril, disintegrant,
The ratio of filler, lubricant and adhesive, it is ensured that ivermectin, mebendazole, toltrazuril can be equably
It is dispersed in each excipient substance, the compound anti-parasitic preparation of the uniformity preferably can be made, and with preferably using effect
Fruit and security performance.
In addition, the filler in the present invention uses lactose, microcrystalline cellulose and maltodextrin, and by controlling lactose, micro-
The mass ratio of crystalline cellulose and maltodextrin is (50-80)：(5-10)：(1-10), its filler being collectively forming have suitable
Suitable caking property and mobility, it is ensured that ivermectin, mebendazole and toltrazuril can be dispersed, and then prepare shape
Into compound anti-parasitic preparation the uniformity it is preferable.In addition, the filler that lactose, microcrystalline cellulose and maltodextrin are formed
Hardness it is suitable, it is preferable to prepare the dissolving out capability of main ingredient in the compound anti-parasitic preparation of formation, and then the compound anti-parasitic
The using effect and security performance of preparation are all preferable.
A kind of preparation method of compound anti-parasitic preparation is provided in addition, there is a need to.
A kind of preparation method of compound anti-parasitic preparation, comprises the following steps：
1) weigh and sieve：Ivermectin, mebendazole, toltrazuril and disintegration are weighed by above-mentioned parts by weight point
The auxiliary materials such as agent, filler, lubricant, adhesive, the ivermectin weighed, mebendazole, toltrazuril and auxiliary material are distinguished
Crushed and handled by the mesh sieve of 60 mesh -120.Alternatively, the auxiliary material also includes flavor enhancement and preservative, and by upper
State parts by weight and weigh flavor enhancement and preservative respectively.
2) ivermectin solid dispersion body is prepared：Ivermectin after sieving is added in absolute ethyl alcohol and is completely dissolved,
The filler added after the sieving of part is well mixed, and drying, crushing and sieving processing, ivermectin solid dispersion is made
Body, wherein, the content of ivermectin described in ivermectin solid dispersion body is 1%-5%.
In one embodiment, the temperature of drying is 50 DEG C -60 DEG C, and the mesh number of sieving is the mesh of 60 mesh -120.
In one embodiment, can also include adding preservative into absolute ethyl alcohol the step dissolved in step 2)
Suddenly.
Specifically, ivermectin, preservative are dissolved in ethanol in tubbing, ensure that dissolving is complete, added part and fill out
Agent mixing is filled, about 4-5 hours is dried in 55 DEG C in baking oven -60 DEG C of drying, crushes, cross 100 mesh sieves, be made and contain 1% ivermectin
Solid dispersions.
3) binder solution is prepared：Adhesive after step 1) is sieved is added in solvent, is prepared into binder solution.
Alternatively, the concentration of the binder solution is 0.1% (w/v) -10% (w/v).
Specifically, by step 1) sieve after PVP be added to the water with concentration be 3% (w/v) PVP water
Solution.
4) softwood is prepared：By the mebendazole after sieving, the toltrazuril after sieving, the filler after remaining sieving, mistake
Disintegrant and ivermectin solid dispersion body after sieve are well mixed by the equivalent method of progressively increasing, and it is molten to add described adhesive
Liquid, softwood is made.Alternatively, the softwood can be held agglomerating, and light pressure dissipates.
In one embodiment, step 4) also includes flavor enhancement being added to the step of being mixed in preparing tank.
Specifically, by toltrazuril, mebendazole, disintegrant, remaining filler, flavor enhancement, ivermectin solid point
Granular media etc. is progressively increased by equivalent to be mixed in method input mixer, and adds binder solution, softwood is made.
5) pelletize：Softwood prepared by step 4) is pelletized, dry and whole grain, particle is made.Wherein, particle
Water content is 2%-7%.
Specifically, softwood is crossed into 20 mesh sieves through oscillating granulator and grain is made, and be put into 55 DEG C of -60 DEG C of dryings in baking oven
About 3-4 hours, drying course will stir back and forth, be heated evenly it, avoid the phenomenon of overdrying or overly moist, moisture control is existed
5%.After 24 mesh sieves, particle is made.
6) film-making：Lubricant after step 1) is sieved is added in particle prepared by step 5), and is mixed, tabletting,
Produce compound anti-parasitic preparation.Wherein, the hardness of the compound anti-parasitic preparation is 1kgf-7kgf.Such as the Compound Resisting is parasitic
The hardness of worm preparation can be, but be not limited to 1kgf, 1.5kgf, 2kgf, 2.5kgf, 3kgf, 3.5kgf, 4kgf,
4.5kgf, 5kgf, 5.5kgf, 6kgf, 6.5kgf or 7kgf.
Specifically, particle is added lubricant and knocks down two-dimensional motion mixer and always mix timing, then by total mixed particle
It is transferred between tabletting and carries out tabletting, produces compound anti-parasitic preparation.
The preparation method of heretofore described compound anti-parasitic preparation, can significantly improve compound anti-parasitic system
The uniformity and dissolution rate of agent, effectively improve the effectiveness and reliability of medicine.In compound anti-parasitic of the present invention
In the preparation method of preparation, by ivermectin, mebendazole, toltrazuril, disintegrant, filler, lubricant and adhesive
Handled after crushing respectively with the mesh sieve of 60 mesh -120, to ensure that the particle diameter of each raw material is smaller and uniform, it is ensured that Yi Wei after mixing
The content of rhzomorph, mebendazole and toltrazuril is uniform, and obtained compound anti-parasitic preparation is more fine and smooth uniform, and it has
The dissolution rate for imitating composition is accelerated.In addition, the particle diameter of ivermectin, mebendazole, toltrazuril is relatively small, surface area compared with
Greatly, its solubility property is preferable.
By the way that the ivermectin after sieving is added in absolute ethyl alcohol, ivermectin can be carried out in absolute ethyl alcohol
Fully dissolving, then be well mixed with the filler after the sieving of part, drying, crushing and sieving processing, Yi Wei bacterium are made
Plain solid dispersions.Ivermectin can be dispersed in the ivermectin solid dispersion body, and it is mixed with each raw material to expand it
It splice grafting contacting surface, can uniformly be distributed in auxiliary material, effectively increase the uniformity of compound anti-parasitic preparation.By using
The equivalent method of progressively increasing is well mixed mebendazole, toltrazuril, filler and ivermectin solid dispersion body, further has
Effect improves the uniformity of obtained compound anti-parasitic preparation.
By controlling the concentration of binder solution it is 0.1% (w/v) -10% (w/v) in the present invention, it is ensured that Compound Resisting is posted
Infested preparation has suitable viscosity, can reduce the contact angle of compound anti-parasitic preparation, makes it easier to soak, effectively changes
The secondary disintegration of kind compound anti-parasitic preparation, so as to significantly improve the dissolution rate of compound anti-parasitic preparation.
It is 1%- by controlling the water content of particle in heretofore described compound anti-parasitic formulation preparation method
5%.The particle has the preferable uniformity and mobility, and ivermectin content distribution is uniform, and then effectively increases Compound Resisting
The uniformity of parasite preparations.
In heretofore described compound anti-parasitic formulation preparation method, by controlling compound anti-parasitic preparation
Hardness is 1kgf-7kgf, it is ensured that compound anti-parasitic preparation has preferable specific surface area, porosity and duct rate, can
The disintegration efficiency of compound anti-parasitic preparation is effectively improved, and then with dissolving out capability preferably.
Therefore, the uniformity by compound anti-parasitic preparation made from the preparation method is preferable, effectively improves medicine
Effectiveness and reliability, and the preparation method is simply efficient, is adapted to industrialization to produce, has broad application prospects.
Compound anti-parasitic preparation in the present invention can be used for outer expelling parasite inside the animals such as canine.Such as Compound Resisting
Parasite preparations are chewable tablets, and animal carries out internal expelling parasite by being swallowed after compound anti-parasitic preparation chewing.This is multiple
The using effect and security performance of square antiparasitic formulations are all preferable.
It is specific embodiment below：
Embodiment 1~13
The composition of compound anti-parasitic preparation is as shown in table 1 in embodiment 1~13.Numerical value corresponding to various raw materials in table 1
For the parts by weight of the raw material.
The composition of the compound anti-parasitic preparation of table 1
1. embodiment 1-7 preparation method is as follows：
1) ivermectin, mebendazole, toltrazuril, PVPP, breast are weighed respectively by the above-mentioned parts by weight
Sugar, microcrystalline cellulose, maltodextrin, beef flavor, magnesium stearate, PVP and ethyl-para-hydroxybenzoate.By what is weighed
Each raw material is crushed and handled by 100 mesh sieves respectively.
2) ivermectin and ethyl-para-hydroxybenzoate are added in absolute ethyl alcohol is completely dissolved it, and adds again
Enter portion of Lactose to be well mixed, the drying process 4-5 hours at a temperature of in baking oven 55 DEG C -60 DEG C, crush, and through 100 mesh sieves
Sieving is handled, and the ivermectin solid dispersion body containing 1% ivermectin is made.
3) PVP by step 1) sieving is added in purified water, and it is water-soluble to be prepared into the PVP that concentration is 3% (w/v)
Liquid.
4) by step 1) sieve after mebendazole, toltrazuril, PVPP, remaining lactose, maltodextrin,
Ivermectin solid dispersion body prepared by microcrystalline cellulose, beef flavor and step 2) is mixed by the equivalent method of progressively increasing, and
Add the PVP aqueous solution that concentration prepared by step 3) is 3% (w/v) to be mixed in preparing tank, softwood is made.This is soft
Material can be held agglomerating, and light pressure dissipates.
5) softwood is crossed into the processing of 20 mesh sieves through oscillating granulator, wet granular is made.Wet granular is placed on baking again
55 DEG C of -60 DEG C of dryings -4 hours about 3 hours in case, drying course will stir back and forth, be heated evenly it, avoid overdrying or mistake
Wet phenomenon, make moisture control 5%.The particle dried is crossed into 24 mesh sieves again, carries out whole grain, particle is made.
6) magnesium stearate after step 1) is sieved is added in particle, and is knocked down two-dimensional motion mixer and always mixed, then will
Total mixed particle carries out tabletting between being transferred to tabletting, produces compound anti-parasitic preparation 1-7.Wherein, the compound anti-parasitic
The hardness of preparation is 2.5 ± 1kgf.
2. embodiment 8-10 preparation method is as follows：
1) ivermectin, mebendazole, toltrazuril, PVPP, breast are weighed respectively by the above-mentioned parts by weight
Sugar, magnesium stearate and PVP.Each raw material weighed is crushed respectively and handled by 100 mesh sieves.
2) ivermectin is added in absolute ethyl alcohol and be completely dissolved, and added portion of Lactose and be well mixed, in baking
Drying process 4-5 hours at a temperature of 55 DEG C -60 DEG C in case, crush, and handled through 100 mesh sieves, be made and contain 1% Yi Wei
The ivermectin solid dispersion body of rhzomorph.
3) PVP after step 1) is sieved is added in purified water, is prepared into the PVP water that concentration is 3% (w/v)
Solution.
4) mebendazole, toltrazuril, PVPP, remaining lactose and step 2) after step 1) is sieved
The ivermectin solid dispersion body of preparation is mixed by the equivalent method of progressively increasing, and the concentration for adding step 3) preparation is 3% (w/
V) the PVP aqueous solution is mixed in preparing tank, and softwood is made.The softwood can be held agglomerating, and light pressure dissipates.
5) softwood is crossed into the processing of 20 mesh sieves through oscillating granulator, wet granular is made.Wet granular is placed on baking again
55 DEG C of -60 DEG C of dryings -4 hours about 3 hours in case, drying course will stir back and forth, be heated evenly it, avoid overdrying or mistake
Wet phenomenon, make moisture control 5%.The particle dried is crossed into 24 mesh sieves again, carries out whole grain, particle is made.
6) magnesium stearate after step 1) is sieved is added in particle, and is knocked down two-dimensional motion mixer and always mixed, then will
Total mixed particle carries out tabletting between being transferred to tabletting, produces compound anti-parasitic preparation 8-10.Wherein, the Compound Resisting is parasitic
The hardness of worm preparation is 2.5 ± 1kgf.
3. embodiment 11-13 preparation method is as follows：
1) ivermectin, mebendazole, toltrazuril, PVPP, breast are weighed respectively by the above-mentioned parts by weight
Sugar, beef flavor, magnesium stearate, ethyl-para-hydroxybenzoate and PVP.Each raw material weighed is crushed simultaneously respectively
Handled by 100 mesh sieves.
2) ivermectin and ethyl-para-hydroxybenzoate are added in absolute ethyl alcohol and are completely dissolved, and add portion
Divide lactose to be well mixed, the drying process 4-5 hours at a temperature of in baking oven 55 DEG C -60 DEG C, crush, and through 100 mesh sieves
Processing, the ivermectin solid dispersion body containing 1% ivermectin is made.
3) PVP after step 1) is sieved is added in purified water, is prepared into the PVP water that concentration is 3% (w/v)
Solution.
4) by step 1) sieve after mebendazole, toltrazuril, PVPP, beef flavor, remaining lactose with
And ivermectin solid dispersion body prepared by step 2) is mixed by the equivalent method of progressively increasing, and add the concentration of step 3) preparation
The PVP aqueous solution for 3% (w/v) is mixed in preparing tank, and softwood is made.The softwood can hold agglomerating, light pressure
Dissipate.
5) softwood is crossed into the processing of 20 mesh sieves through oscillating granulator, wet granular is made.Wet granular is placed on baking again
55 DEG C of -60 DEG C of dryings -4 hours about 3 hours in case, drying course will stir back and forth, be heated evenly it, avoid overdrying or mistake
Wet phenomenon, make moisture control 5%.The particle dried is crossed into 24 mesh sieves again, carries out whole grain, particle is made.
6) magnesium stearate after step 1) is sieved is added in particle, and is knocked down two-dimensional motion mixer and always mixed, then will
Total mixed particle carries out tabletting between being transferred to tabletting, produces compound anti-parasitic preparation 11-13.Wherein, the Compound Resisting is parasitic
The hardness of worm preparation is 2.5 ± 1kgf.
Comparative example 1
This comparative example is tablet 1, and each raw material is weighed with following percentage by weight：0.08 part of ivermectin, mebendazole 30
Part, 50 parts of toltrazuril, 120 parts of lactose, 20 parts of PVPP, 15 parts of PVP and 2 parts of magnesium stearate.The comparative example 1
Preparation method it is identical with the preparation method of embodiment 8.
Comparative example 2
This comparative example is tablet 2, and the difference of the component and the component of embodiment 8 of comparative example 2 is：It is not added with toluene miaow
Azoles and toltrazuril, other components and proportioning are same as Example 8.The preparation method of the comparative example 2 is same as Example 8.
Comparative example 3
This comparative example is tablet 3, and the difference of the component and the component of embodiment 8 of comparative example 3 is：It is not added with Yi Wei bacterium
Element and toltrazuril, other components are same as Example 8 with matching.The preparation method of the comparative example 3 is same as Example 8.
Comparative example 4
This comparative example is tablet 4, and the difference of the component and the component of embodiment 8 of comparative example 4 is：It is not added with Yi Wei bacterium
Element and mebendazole, other components and proportioning are same as Example 8.The preparation method of the comparative example 4 is same as Example 8.
Comparative example 5
This comparative example is tablet 5, the component and proportioning of comparative example 5 and the component of embodiment 8 and proportioning all same.Difference
It is：Ivermectin and being added in absolute ethyl alcohol is not completely dissolved in preparation method, but she after step 1) is sieved
Dimension rhzomorph, toltrazuril, mebendazole, PVPP and lactose are directly mixed, and the concentration for adding preparation is
3% (w/v) the PVP aqueous solution is mixed in preparing tank, and softwood is made.
The dissolution rate test of effete test embodiment 1
6, the Compound Resisting parasitism of the preparation of embodiment 8 in the compound anti-parasitic preparation 1 that respectively prepared by Example 1
6 progress dissolutions in tablet 5 prepared by 6 in worm preparation 8,6 in the tablet 1 for preparing of comparative example 1 and comparative example 5
Degree test, test method：According to dissolution rate and drug release determination method (《Republic of China Veterinary Pharmacopoeia version in 2015》(one
Portion) annex 0931) progress of the second method.Test result is as shown in table 2.
The dissolution rate test result of table 2
Conclusion：It can be seen from the data of table 2, embodiment 1 prepare compound anti-parasitic preparation 1 and embodiment 8 prepare
The each component of compound anti-parasitic preparation 8 (ivermectin, mebendazole, toltrazuril) is all higher than 80%, and meeting dissolution rate will
Ask, and the equal conspicuousness of dissolution rate of the tablet 5 of tablet 1 and comparative example 5 preparation prepared relative to comparative example 1 improves, and contrast
The ivermectin of tablet 1, the mebendazole dissolution rate of the preparation of example 1 are unqualified.
The uniformity of effete test embodiment 2 is tested
The Compound Resisting for respectively preparing 10 in compound anti-parasitic preparation 1 prepared by embodiment 1, embodiment 8 is parasitic
10 progress uniformity tests in tablet 1 prepared by 10 in worm preparation 8 and comparative example 1, test method：According to content
Uniformity test method (《Republic of China Veterinary Pharmacopoeia version in 2015》(one) annex 0941) carry out.Test result such as table 3
It is shown.
The uniformity test result of table 3
Conclusion：It can be seen from the data of table 3, embodiment 1 prepare compound anti-parasitic preparation 1 and embodiment 8 prepare
The uniformity of dosage units of compound anti-parasitic preparation 8 is very good, and its uniformity (A+2.2S) is respectively less than 15, meets uniformity requirements, and
The equal conspicuousness of the uniformity of the tablet 1 prepared relative to comparative example 1 improves, and each component (ivermectin, the toluene of comparative example 1
Imidazoles, toltrazuril) uniformity of dosage units is unqualified.
The influence factor of embodiment 3 is tested
In order to verify stability of the compound anti-parasitic preparation under extraordinary environment in the present invention, prepared by Example 1
Compound anti-parasitic preparation 8 prepared by compound anti-parasitic preparation 1 and embodiment 8 carries out hot test, intense light irradiation experiment respectively
And the experiment of the influence factor such as high wet test, test method is according under material medicine and preparation stability test direction principle item
Pharmaceutical preparation influence factor test method (《Republic of China Veterinary Pharmacopoeia (version in 2015)》(one) annex 9001) enter
OK, specific test method is as follows：
3.1 hot test
The good sample of bubble-cap is placed 10 days at a temperature of 60 DEG C, in the 5th day and the 10th day sampling analysis.
3.2 intense light irradiations are tested
The good sample of bubble-cap is placed in the stable case of sample, placed 10 days under the conditions of 4500 ± 500lx of illumination, the 5th
It and the 10th day sampling analysis.
3.3 high wet tests
The good sample of bubble-cap is placed under 90% damp condition and places the decentralization of 10 days conditions and puts 10 days, at the 5th day and the 10th
Its sampling analysis.
Character, ivermectin content, dissolution rate to samples taken etc. carry out observation detection, and are carried out with the result of 0 day
Compare, table 4 is compound anti-parasitic preparation influence factor result of the test.
The influence factor result of the test of table 4
Conclusion：It can be seen from table 4 detects data, compound anti-parasitic preparation prepared by embodiment 1 and embodiment 8 is 60
Every Testing index has no significant change under DEG C high temperature, 4500 ± 500lx intense light irradiation and 90% ± 5% high humidity environment, matter
Measure relatively stable, meet stability requirement.
The accelerated stability of effete test embodiment 4 is tested
In order to verify compound anti-parasitic preparation accelerated stability in the present invention, Compound Resisting prepared by Example 1 is parasitic
Compound anti-parasitic preparation 8 prepared by worm preparation 1 and embodiment 8 is appropriate, respectively 40 ± 2 DEG C of temperature, relative humidity 75% ±
Placed under conditions of 5% 6 months carry out accelerated stability test, 1st month during experiment, 2 months, 3 months, 6 month in and month out
End is separately sampled once, character, each component (ivermectin, mebendazole, toltrazuril) content and dissolution to samples taken
Degree etc. carries out observation detection, and compared with the result of 0 day, test method is tested according to material medicine and preparation stability
Under guideline item pharmaceutical preparation accelerated test method (《Republic of China Veterinary Pharmacopoeia (version in 2015)》(one) is attached
9001) record is carried out.Table 5 is the accelerated stability test result of compound anti-parasitic preparation.
The accelerated stability test result of table 5
Conclusion：According to table 5 detect data understand, embodiment 1 and embodiment 8 preparation compound anti-parasitic preparation
Every Testing index has no significant change under conditions of 40 ± 2 DEG C of temperature, relative humidity 75% ± 5%, and quality is relatively stable,
Meet stability requirement.
The efficacy test of effete test embodiment 5
Example 1 prepares compound anti-parasitic preparation 1, compound anti-parasitic preparation 8 prepared by embodiment 8 and contrast
Tablet 1-5 prepared by example 1-5 carries out anti parasitic efficacy test.
It is visible in dog plant of Huadu of Guangdong Province, selection itch, local skin dothienesis, hair follicle inflammation, hair of leafing through
The dog of black parasite excreta or parasite polypide only 80, it is judged as parasitic disease dog, every 10 are included into one group, respectively
For A, B, C, D, E, F, G and H group.A groups press 1/5kg oral administered compounds antiparasitic formulations 1, and B groups press 1/5kg oral administered compounds
Antiparasitic formulations 7, C groups press tablet 1 prepared by 1/5kg oral contrasts example 1, and D groups are prepared by 1/5kg oral contrasts example 2
Tablet 2, E groups press 1/5kg oral contrasts example 3 prepare tablet 3, F groups by 1/5kg oral contrasts example 4 preparation piece
Agent 4, G groups press tablet 5 prepared by 1/5kg oral contrasts example 5, and H groups are not administered, as blank control group.A groups, B groups, C groups,
D groups, E groups, F groups, G groups and the field stable breeding of H components avoid cross infection..The 5th day after administration, gather respectively within the 10th day, the 15th day
Each group fecal specimens carry out microscopy.Testing result is as shown in table 6.
The excrement testing result of table 6
Redution of eggs (%)={ worm's ovum number before [worm's ovum number after worm's ovum number-administration before administration]/administration } * 100%
Worm's ovum is with respect to slip (%)={ [not administration group nematode worm's ovum number-administration group nematode worm's ovum number]/not administration group
Nematode worm's ovum number } * 100%
Conclusion：The compound anti-parasitic preparation 8 that the embodiment 1 prepares compound anti-parasitic preparation 1 and prepared by embodiment 8
It is significantly increased relative to the comparative example 1-5 tablet 1-5 anthelminthic effects prepared, especially to nematode, tapeworm, coccidia
Purge ratio performance is good.Wherein, when taking compound anti-parasitic preparation 1 the 5th day, worm's ovum is largely reduced, and is not had at the 15th day
Check hookworm, roundworm, whipworm, coccidia worm's ovum.In addition, using compound anti-parasitic preparation 1 and compound anti-parasitic system
During agent 8, animal does not occur obvious uncomfortable reaction.Therefore, the Yi Wei in the compound anti-parasitic preparation of the invention
Rhzomorph, mebendazole and toltrazuril are compound, can produce preferably collaboration wide spectrum expelling parasite insecticidal effect, can effectively drive
The parasites such as dog nematode, tapeworm, coccidia are killed, the compound anti-parasitic preparation has preferably anti parasitic effect.
Each technical characteristic of embodiment described above can be combined arbitrarily, to make description succinct, not to above-mentioned reality
Apply all possible combination of each technical characteristic in example to be all described, as long as however, the combination of these technical characteristics is not deposited
In contradiction, the scope that this specification is recorded all is considered to be.
Embodiment described above only expresses the several embodiments of the present invention, and its description is more specific and detailed, but simultaneously
Can not therefore it be construed as limiting the scope of the patent.It should be pointed out that come for one of ordinary skill in the art
Say, without departing from the inventive concept of the premise, various modifications and improvements can be made, these belong to the guarantor of the present invention
Protect scope.Therefore, the protection domain of patent of the present invention should be determined by the appended claims.
Claims (10)
1. a kind of compound anti-parasitic preparation, it is characterised in that be mainly prepared by each raw material of following parts by weight：Yi Wei bacterium
0.04 part -0.1 part of element, 5 parts -10 parts of mebendazole, 5 parts -15 parts of toltrazuril, 3 parts -10 parts of disintegrant, 61 part -91 of filler
0.3 part -1 part of part, 1 part -3 parts of lubricant and adhesive.
2. compound anti-parasitic preparation according to claim 1, it is characterised in that also including parts by weight be 1 part -4 parts
Flavor enhancement and the preservative that parts by weight are 0.01 part -0.04 part.
3. compound anti-parasitic preparation according to claim 2, it is characterised in that prepared by each raw material of following parts by weight
Form：0.05 part -0.1 part of ivermectin, 7 parts -9 parts of mebendazole, 8 parts -12 parts of toltrazuril, 5 parts -8 parts of disintegrant, filling
0.01 part of 61 parts -71 parts of agent, 1 part -2 parts of lubricant, 0.5 part -0.8 part of adhesive, 1 part -2 parts of flavor enhancement and preservative -
0.03 part.
4. according to the compound anti-parasitic preparation described in claim any one of 1-3, it is characterised in that the disintegrant is carboxylic first
Base sodium starch, PVPP, Ac-Di-Sol, ethyl cellulose, methylcellulose, lauryl sodium sulfate and
One or more in polyvinylpyrrolidone.
5. according to the compound anti-parasitic preparation described in claim any one of 1-3, it is characterised in that the filler is anhydrous
One or more in Icing Sugar, lactose, sucrose, starch, microcrystalline cellulose and maltodextrin.
6. compound anti-parasitic preparation according to claim 5, it is characterised in that the filler is lactose, crystallite fibre
Dimension element and maltodextrin, wherein, the lactose, the mass ratio of the microcrystalline cellulose and the maltodextrin are (50-80)：
(5-10)：(4-8).
7. compound anti-parasitic preparation according to claim 6, it is characterised in that the lactose, the microcrystalline cellulose
Mass ratio with the maltodextrin is 52：10：5.
8. according to the compound anti-parasitic preparation described in claim any one of 2-3, it is characterised in that the flavor enhancement is beef
Essence and/or chicken essence；The lubricant is the one or more in magnesium stearate, talcum powder and superfine silica gel powder；It is described viscous
Mixture is the one or more in sodium carboxymethylcellulose, starch slurry, hydroxypropyl methylcellulose or PVP；The preservative is pair
One or more in hydroxybenzoic acid esters, butylated hydroxy anisole or dibutyl hydroxy toluene.
9. a kind of preparation method of compound anti-parasitic preparation, it is characterised in that comprise the following steps：
By any one of the claim 1-8 parts by weight weigh respectively ivermectin, mebendazole, toltrazuril, disintegrant,
Filler, lubricant and adhesive；
Each raw material weighed is subjected to pulverization process respectively, and handled by the mesh sieve of 60 mesh -120；
The ivermectin after sieving is added in absolute ethyl alcohol and is completely dissolved, the filling added after the sieving of part
Agent is well mixed, and drying, crushing and sieving processing, ivermectin solid dispersion body is made, wherein, the ivermectin solid
The content of ivermectin described in dispersion is 1%-5%；
Described adhesive after sieving is added in solvent, prepares and obtains the bonding that concentration is 0.1% (w/v) -10% (w/v)
Agent solution；
By the mebendazole after sieving, the toltrazuril after sieving, the disintegrant after sieving, remaining sieving
The filler and the ivermectin solid dispersion body afterwards is well mixed by the equivalent method of progressively increasing, and adds the bonding
Agent solution, softwood is made；
The softwood is pelletized, dry and whole grain, particle is made, wherein, the water content of the particle is 2%-7%；
The lubricant after sieving is well mixed with the particle, through compressing tablet process, produces compound anti-parasitic preparation, its
In, the hardness of the compound anti-parasitic preparation is 1kgf-7kgf.
10. the preparation method of compound anti-parasitic preparation according to claim 9, it is characterised in that the ivermectin
Mass ratio with the absolute ethyl alcohol is 1：(20-40).
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109364089A (en) * | 2018-11-27 | 2019-02-22 | 佛山市正典生物技术有限公司 | It is a kind of with the composition and preparation method thereof for killing helminth effect |
| CN110314148A (en) * | 2019-05-07 | 2019-10-11 | 安徽金太阳生化药业有限公司 | A kind of preparation method of phosphoric acid hydrogen calcium tablet |
| WO2023283683A1 (en) * | 2021-07-12 | 2023-01-19 | The University Of Sydney | Compositions of ivermectin and uses thereof |
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| CN101703776A (en) * | 2009-09-28 | 2010-05-12 | 洛阳惠中兽药有限公司 | Method for preparing anti-infective agent long-acting injection |
| CN105267230A (en) * | 2015-10-12 | 2016-01-27 | 青岛农业大学 | Compound fenbendazole tablet |
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| CN101703776A (en) * | 2009-09-28 | 2010-05-12 | 洛阳惠中兽药有限公司 | Method for preparing anti-infective agent long-acting injection |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN109364089A (en) * | 2018-11-27 | 2019-02-22 | 佛山市正典生物技术有限公司 | It is a kind of with the composition and preparation method thereof for killing helminth effect |
| CN110314148A (en) * | 2019-05-07 | 2019-10-11 | 安徽金太阳生化药业有限公司 | A kind of preparation method of phosphoric acid hydrogen calcium tablet |
| WO2023283683A1 (en) * | 2021-07-12 | 2023-01-19 | The University Of Sydney | Compositions of ivermectin and uses thereof |
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Application publication date: 20180216 |