CN107753498A - Compound ivermectin tablet and preparation method thereof - Google Patents
Compound ivermectin tablet and preparation method thereof Download PDFInfo
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- CN107753498A CN107753498A CN201711053064.8A CN201711053064A CN107753498A CN 107753498 A CN107753498 A CN 107753498A CN 201711053064 A CN201711053064 A CN 201711053064A CN 107753498 A CN107753498 A CN 107753498A
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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
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/4985—Pyrazines or piperazines ortho- or peri-condensed with heterocyclic ring systems
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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
- A61K9/2027—Organic macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates
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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
- A61K9/2095—Tabletting processes; Dosage units made by direct compression of powders or specially processed granules, by eliminating solvents, by melt-extrusion, by injection molding, by 3D printing
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Abstract
The present invention relates to a kind of compound ivermectin tablet and preparation method thereof.The compound ivermectin tablet is mainly prepared by each raw material of following parts by weight：1 part of 0.05 part of ivermectin 0.01 part, 10 parts of Fenbendazole 5 part, 5 parts of praziquantel 2 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 ivermectin tablet is high and using effect is good.
Description
Technical field
The present invention relates to anti-parasite medicine technical field, more particularly to a kind of compound ivermectin tablet and its 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 people
Flat life increase enjoyment, and the lonely and pressure of people's heart can be alleviated.But Canis is in mammal, easily
Suffer from the parasitic diseases such as nematode, tapeworm, fluke, if can not get timely medical treatment, not only influence the health of canine, can also increase the mankind
Infect the risk of parasitic disease.Further, since cross-infection also easily occurs in daily life for canine and other mammals
Germ parasite, 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 novel low-toxicity antibioticses antiparasitic agent, has to nematode and arthropod and kills effect.It is fragrant
Parbendazole is benzene thibenzazoline class anthelmintic, and effect is killed to nematode, fluke and tapeworm.Praziquantel has to fluke and tapeworm
Kill effect.But the Traits change between ivermectin, Fenbendazole and praziquantel is larger, and itself and each excipient substance it
Between Traits change it is also larger.Therefore, ivermectin, Fenbendazole and praziquantel are difficult to compound obtained tablet.
The content of the invention
Based on this, it is necessary to provide the compound ivermectin tablet and its preparation side that a kind of uniformity is high and using effect is good
Method.
A kind of compound ivermectin tablet, mainly it is prepared by each raw material of following parts by weight：0.01 part of ivermectin-
0.05 part, 5 parts -10 parts of Fenbendazole, 2 parts -5 parts of praziquantel, 3 parts -10 parts of disintegrant, 61 parts -91 parts of filler, lubricant 1
Part -3 parts and 0.3 part -1 part of adhesive.
In addition to 0.01 part of 1 part -4 parts of flavor enhancement and preservative in one of the embodiments, in parts by weight, -
0.04 part.
In one of the embodiments, it is prepared by each raw material of following parts by weight：0.03 part -0.04 of ivermectin
Part, 7 parts -8 parts of Fenbendazole, 4 parts -5 parts of praziquantel, 5 parts -8 parts of disintegrant, 70 parts -85 parts of filler, 1 part -2 of lubricant
Part, 0.5 part -1 part of adhesive, 1 part -2 parts of flavor enhancement and 0.01 part -0.03 part of preservative.
In one of the embodiments, the disintegrant is sodium carboxymethyl starch, PVPP, cross-linked carboxymethyl fiber
One or more in plain sodium, ethyl cellulose, methylcellulose, lauryl sodium sulfate and polyvinylpyrrolidone.
In one of the embodiments, the filler is anhydrous Icing Sugar, lactose, sucrose, starch, microcrystalline cellulose and wheat
One or more in bud dextrin.
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
60：10：5.
In one of the embodiments, the flavor enhancement is beef flavor and/or chicken essence；The lubricant is tristearin
One or more in sour magnesium, talcum powder and superfine silica gel powder；Described adhesive is sodium carboxymethylcellulose, starch slurry, hydroxypropyl first
One or more in cellulose or PVP；The preservative is parabens, butylated hydroxy anisole or two
One or more in butylated hydroxytoluene.
Compound ivermectin tablet in the present invention is the Formulation being processed into by main ingredient and suitable excipient substance.
Count in parts by weight, the main ingredient includes 2 part -5 of 0.01 part -0.05 part of ivermectin, 5 parts -10 parts of Fenbendazole and praziquantel
Part, the excipient substance include 0.3 part of 3 parts -10 parts of disintegrant, 61 parts -91 parts of filler, 1 part -3 parts of lubricant and adhesive -
1 part.Ivermectin, Fenbendazole and praziquantel in the compound ivermectin tablet is compound, can produce preferable collaboration
Wide spectrum expelling parasite insecticidal effect, it can effectively kill the parasites such as nematode, tapeworm, fluke disease.The compound ivermectin tablet passes through
Control the ratio of ivermectin, Fenbendazole, praziquantel, disintegrant, filler, lubricant and adhesive, it is ensured that she
Dimension rhzomorph, Fenbendazole, praziquantel can be evenly dispersed in each excipient substance, effectively increase compound ivermectin tablet
The uniformity, and then there is preferable using effect 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, Fenbendazole and praziquantel can be dispersed, and then prepare and formed
Compound ivermectin tablet the uniformity it is preferable.In addition, the filler that lactose, microcrystalline cellulose and maltodextrin are formed is hard
Degree is suitable, and it is preferable to prepare the dissolving out capability of main ingredient in the compound ivermectin tablet of formation, and then the compound ivermectin tablet
Using effect and security performance it is all preferable.
The disintegrant of the present invention is from sodium carboxymethyl starch, PVPP, Ac-Di-Sol, ethyl cellulose
During one or more in element, methylcellulose, lauryl sodium sulfate and polyvinylpyrrolidone, it is preferable that it is disintegrated effect,
The dissolution of ivermectin is helped lend some impetus to, and then further increases the using effect and security of compound ivermectin tablet
Energy.When disintegrant is PVPP, it can make disintegration of tablet rapid, not only be easier to soak medicaments uniformity, Er Qieneng
Hydrophobic drug surface is changed into hydrophily, further promote the dissolution of medicine and the disintegration of tablet.
A kind of preparation method of compound ivermectin tablet is provided in addition, there is a need to.
A kind of preparation method of compound ivermectin tablet, comprises the following steps：
Ivermectin, Fenbendazole, praziquantel, disintegrant, filler, lubrication are weighed respectively by parts by weight described above
Agent 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, is added described after the sieving of part
Filler is well mixed, and drying, crushing and sieving processing, ivermectin solid dispersion body is made, wherein, the ivermectin
The content of ivermectin described in solid dispersions is 1%-5%；
Described adhesive after sieving is added in solvent, it is 0.1% (w/v's) -10% (w/v) to prepare and obtain concentration
Binder solution；
By the Fenbendazole after sieving, the praziquantel after sieving, the disintegrant after sieving, remaining mistake
The filler and the ivermectin solid dispersion body after sieve are well mixed by the equivalent method of progressively increasing, and are added described viscous
Mixture 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 ivermectin piece
Agent, wherein, the hardness of the compound ivermectin tablet 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 ivermectin tablet, can significantly improve compound ivermectin tablet
The uniformity and dissolution rate, effectively improve the effectiveness and reliability of medicine.In compound ivermectin piece of the present invention
In the preparation method of agent, ivermectin, Fenbendazole, praziquantel, disintegrant, filler, lubricant and adhesive are distinguished
Handled after crushing 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 ivermectin after mixing,
The content of Fenbendazole and praziquantel is uniform, and obtained compound ivermectin tablet is more fine and smooth uniform, its active ingredient
Dissolution rate is accelerated.In addition, the particle diameter of ivermectin, Fenbendazole, praziquantel is relatively small, surface area is larger, its dissolubility
Can be preferably.
By the way that the ivermectin after sieving is added in absolute ethyl alcohol, ivermectin can be filled in absolute ethyl alcohol
Divide dissolving, then be well mixed with the filler after the sieving of part, drying, crushing and sieving processing, obtained ivermectin
Solid dispersions.Ivermectin can be dispersed in the ivermectin solid dispersion body, expands its mixing with each raw material
It contact surface, can uniformly be distributed in auxiliary material, effectively increase the uniformity of compound ivermectin tablet.By using equivalent
The method of progressively increasing is well mixed Fenbendazole, praziquantel, disintegrant, filler and ivermectin solid dispersion body, further has
Effect improves the uniformity that compound ivermectin tablet is prepared.
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 Yi Wei bacterium
Plain piece agent has suitable viscosity, can reduce the contact angle of compound ivermectin tablet, makes it easier to soak, and effectively improves multiple
The secondary disintegration of square ivermectin tablet, so as to significantly improve the dissolution rate of compound ivermectin tablet.
It is 1%- by controlling the water content of particle in heretofore described compound ivermectin method for preparing tablet thereof
5%.The particle has the preferable uniformity and mobility, and ivermectin content distribution is uniform, so effectively increase compound she
Tie up the uniformity of rhzomorph tablet.
In heretofore described compound ivermectin method for preparing tablet thereof, by controlling the hard of compound ivermectin tablet
Spend for 1kgf-7kgf, it is ensured that compound ivermectin tablet has preferable specific surface area, porosity and duct rate, Neng Gouyou
Effect improves the disintegration efficiency of compound ivermectin tablet, and then with dissolving out capability preferably.
In heretofore described compound ivermectin method for preparing tablet thereof, by controlling ivermectin and the anhydrous second
The mass ratio of alcohol is 1：(20-40), it is ensured that absolute ethyl alcohol can preferably dissolve ivermectin, and then ensure ivermectin compared with
It is uniformly dispersed in auxiliary material, obtained compound ivermectin tablet has the preferable uniformity, and then further increases medicine
The performance of thing.
Therefore, the uniformity of compound ivermectin tablet produced by the present invention and dissolution rate are preferable, and then effectively increase
The effectiveness and reliability of medicine.
Compound ivermectin tablet in the present invention can be used for outer expelling parasite inside the animals such as canine.Such as compound Yi Wei
Rhzomorph tablet is chewable tablets, and animal carries out internal expelling parasite by being swallowed after the compound ivermectin tablet is chewed.The compound she
Using effect and the security performance for tieing up rhzomorph tablet 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 hair
It is bright to realize in many different forms, however it is not limited to embodiment described herein.On the contrary, provide these embodiments
Purpose be to make the understanding more thorough and comprehensive to the disclosure.
Unless otherwise defined, all of technologies and scientific terms used here by the article is with belonging to technical field of the invention
The implication that technical staff is generally understood that is identical.Term used in the description of the invention herein is intended merely to description tool
The purpose of the embodiment of body, it is not intended that in the limitation present invention.Term as used herein "and/or" includes one or more phases
The arbitrary and all combination of the Listed Items of pass.
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 ivermectin tablet is to pass through the Formulation being processed into by main ingredient and suitable auxiliary material.The compound she
Dimension rhzomorph tablet is mainly prepared by each raw material of following parts by weight：0.01 part -0.05 part of ivermectin, such as can be,
But it is not limited to 0.01 part, 0.02 part, 0.03 part, 0.04 or 0.05 part；5 parts -10 parts of Fenbendazole, such as can be, but it is unlimited
In 5 parts, 6 parts, 7 parts, 7.5 parts, 8 parts, 9 parts or 10 parts, 2 parts -5 parts of praziquantel, such as can be, but be not limited to 2 parts, 3 parts, 4
Part, 4.5 parts or 5 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, 73.25 parts, 75 parts, 80 parts, 85 parts or 91 parts；
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, but
It is not limited to 0.3 part, 0.4 part, 0.6 part, 0.7 part, 0.8 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.Anti-corrosion
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, 0.04 part.
In one embodiment, the compound ivermectin tablet is mainly prepared by each raw material of following parts by weight：
0.03 part -0.04 part of ivermectin, 7 parts -8 parts of Fenbendazole, 4 parts -5 parts of praziquantel, 5 parts -8 parts of disintegrant, 70 parts of filler -
0.01 part -0.03 part of 85 parts, 1 part -2 parts of lubricant, 0.5 part -1 part of adhesive, 1 part -2 parts of flavor enhancement and preservative.
In one embodiment, it is prepared by each raw material of following parts by weight：0.03 part of ivermectin, Fenbendazole
7.5 parts, 4.5 parts of praziquantel, 7 parts of disintegrant, 73.25 parts of filler, 1 part of flavor enhancement, 1 part of lubricant, 0.7 part of adhesive 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 composition
Dissolve and absorb and play a role rapidly.The disintegrant needs have good water imbibition and dilatancy, so as to realize collapsing for tablet
Solution.Alternatively, the disintegrant is sodium carboxymethyl starch, PVPP, Ac-Di-Sol, ethyl cellulose, first
One or more in base cellulose, lauryl sodium sulfate and polyvinylpyrrolidone etc., its disintegration effect is preferable, contributes to
Promote the dissolution of ivermectin, and then further increase the using effect and security performance of compound ivermectin tablet.Enter one
Alternatively, the disintegrant is PVPP to step, and it can make disintegration of tablet rapid, not only be easier to soak medicaments uniformity, and
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 most
Number medicine does not work, and price is also relatively cheap, and hygroscopicity is small, appearance luster is good.Microcrystalline cellulose is cellulosic sections hydrolysis
Prepared by the less crystallinity cellulose of the degree of polymerization, there is good compressibility, have stronger adhesion, the tablet being pressed into has
It is larger to have hardness.Amylum pregelatinisatum has good mobility, compressibility, self-lubricity and dry adhesive.Dextrin is starch
The general name of intermediate product is hydrolyzed, maltodextrin forms 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, the crystallite
The mass ratio of cellulose and the maltodextrin is (50-80)：(5-10)：(1-10).Alternatively, the lactose, the microcrystalline cellulose
The mass ratio of element and the maltodextrin is 60：10：5.The filler that lactose, microcrystalline cellulose and malt paste are collectively forming has
Suitable caking property and mobility, it is ensured that each main ingredient can be dispersed, and then prepares the compound ivermectin tablet formed
The uniformity is preferable.In addition, the hardness for the filler that lactose, microcrystalline cellulose and maltodextrin are formed is suitable, answering for formation is prepared
The dissolving out capability of square ivermectin tablet Chinese traditional medicine is preferable, and then the compound ivermectin tablet using effect and security performance are all
Preferably.
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 be beef flavor, chicken essence, dog taste flavouring agent, milk powder or
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, drops
Frictional force between low tablet and punch die hole wall.Alternatively, the lubricant is one in magnesium stearate, talcum powder and superfine silica gel powder etc.
Kind is a variety of.
The adhesive is the sticking material of tool, and drug material can link together by its viscosity.Alternatively, this is viscous
Mixture is in sodium carboxymethylcellulose, starch slurry, hydroxypropyl methylcellulose, methylcellulose or ethyl cellulose, PVP etc.
It is 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).As starch slurry be in tablet it is more normal
Adhesive, the concentration of its starch slurry solution matched somebody with somebody are generally 2% (w/v) -10% (w/v)；When material compressibility can it is 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.According to carboxylic first
When base sodium cellulosate is 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, the concentration of its hydroxypropyl methylcellulose aqueous solution prepared is generally
1% (w/v) -6% (w/v).During according to PVP as adhesive, the concentration of its PVP aqueous solution prepared 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 equably
Mixed with auxiliary material, the uniformity of the compound ivermectin tablet of formation is preferable.
Compound ivermectin tablet in the present invention is the Formulation being processed into by main ingredient and suitable excipient substance.
Count in parts by weight, the main ingredient includes 2 part -5 of 0.01 part -0.05 part of ivermectin, 5 parts -10 parts of Fenbendazole and praziquantel
Part, the excipient substance include 0.3 part of 3 parts -10 parts of disintegrant, 61 parts -91 parts of filler, 1 part -3 parts of lubricant and adhesive -
1 part.Ivermectin, Fenbendazole and praziquantel in the compound ivermectin tablet is compound, can produce preferable collaboration
Wide spectrum expelling parasite insecticidal effect, it can effectively kill the parasites such as nematode, tapeworm, fluke.The compound ivermectin tablet passes through control
Ivermectin processed, Fenbendazole, praziquantel, disintegrant, filler, the ratio of lubricant and adhesive, it is ensured that Yi Wei
Rhzomorph, Fenbendazole, praziquantel can be evenly dispersed in each excipient substance, effectively increase compound ivermectin tablet
The uniformity, and then there is preferable using effect 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, Fenbendazole and praziquantel can be dispersed, and then prepare what is formed
The uniformity of compound ivermectin tablet is preferable.In addition, the hardness for the filler that lactose, microcrystalline cellulose and maltodextrin are formed
Suitably, prepare that the dissolving out capability of main ingredient in the compound ivermectin tablet of formation is preferable, and then the compound ivermectin tablet
Using effect and security performance are all preferable.
A kind of preparation method of compound ivermectin tablet is provided in addition, there is a need to.
A kind of preparation method of compound ivermectin tablet, comprises the following steps：
1) weigh and sieve：By above-mentioned parts by weight point weigh ivermectin, Fenbendazole, praziquantel and disintegrant,
The auxiliary materials such as filler, lubricant, adhesive, the ivermectin weighed, Fenbendazole, praziquantel and auxiliary material are subjected to powder respectively
It is broken and pass through the mesh sieve of 60 mesh -120 handle.Alternatively, the auxiliary material also includes flavor enhancement and preservative, and presses above-mentioned parts by weight
Number weighs 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.Can
Selection of land, 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 it is water-soluble
Liquid.
4) softwood is prepared：By the Fenbendazole after sieving, the praziquantel after sieving, the disintegrant after sieving, remaining sieving
Filler and ivermectin solid dispersion body afterwards is well mixed by the equivalent method of progressively increasing, and adds described adhesive solution,
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 praziquantel, Fenbendazole, remaining filler, disintegrant, flavor enhancement, ivermectin solid dispersion
Body etc. progressively increases 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 contains
Water is 2%-7%.
Specifically, softwood is crossed into 20 mesh sieves through oscillating granulator and grain is made, and be put into baking oven 55 DEG C of -60 DEG C of dryings about
3-4 hours, drying course will stir back and forth, be heated evenly it, avoid the phenomenon of overdrying or overly moist, make moisture control 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 ivermectin tablet.Wherein, the hardness of the compound ivermectin tablet is 1kgf-7kgf.Such as compound Yi Wei bacterium
The hardness of plain piece agent 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 ivermectin tablet.
The preparation method of heretofore described compound ivermectin tablet, can significantly improve compound ivermectin tablet
The uniformity and dissolution rate, effectively improve the effectiveness and reliability of medicine.In compound ivermectin piece of the present invention
In the preparation method of agent, ivermectin, Fenbendazole, praziquantel, disintegrant, filler, lubricant and adhesive are distinguished
Handled after crushing 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 ivermectin after mixing,
The content of Fenbendazole and praziquantel is uniform, and obtained compound ivermectin tablet is more fine and smooth uniform, its active ingredient
Dissolution rate is accelerated.In addition, the particle diameter of ivermectin, Fenbendazole, praziquantel is relatively small, surface area is larger, its dissolubility
Can be preferably.
By the way that the ivermectin after sieving is added in absolute ethyl alcohol, ivermectin can be filled in absolute ethyl alcohol
Divide dissolving, then be well mixed with the filler after the sieving of part, drying, crushing and sieving processing, obtained ivermectin
Solid dispersions.Ivermectin can be dispersed in the ivermectin solid dispersion body, expands its mixing with each raw material
It contact surface, can uniformly be distributed in auxiliary material, effectively increase the uniformity of compound ivermectin tablet.By using equivalent
The method of progressively increasing is well mixed Fenbendazole, praziquantel, filler, disintegrant and ivermectin solid dispersion body, further has
Effect improves the uniformity that compound ivermectin tablet is prepared.
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 Yi Wei bacterium
Plain piece agent has suitable viscosity, can reduce the contact angle of compound ivermectin tablet, makes it easier to soak, and effectively improves multiple
The secondary disintegration of square ivermectin tablet, so as to significantly improve the dissolution rate of compound ivermectin tablet.
It is 1%- by controlling the water content of particle in heretofore described compound ivermectin method for preparing tablet thereof
5%.The particle has the preferable uniformity and mobility, and ivermectin content distribution is uniform, so effectively increase compound she
Tie up the uniformity of rhzomorph tablet.
In heretofore described compound ivermectin method for preparing tablet thereof, by controlling the hard of compound ivermectin tablet
Spend for 1kgf-7kgf, it is ensured that compound ivermectin tablet has preferable specific surface area, porosity and duct rate, Neng Gouyou
Effect improves the disintegration efficiency of compound ivermectin tablet, and then with dissolving out capability preferably.
Therefore, the uniformity by compound ivermectin tablet 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 ivermectin tablet in the present invention can be used for outer expelling parasite inside the animals such as canine.Such as compound Yi Wei
Rhzomorph tablet is chewable tablets, and animal carries out internal expelling parasite by being swallowed after compound ivermectin tablet chewing.The compound she
Using effect and the security performance for tieing up rhzomorph tablet are all preferable.
It is specific embodiment below：
Embodiment 1-12
The component of compound ivermectin tablet is as shown in table 1 in embodiment 1-12.Numerical value corresponding to various raw materials is in table 1
The parts by weight of the raw material.
The component of the compound ivermectin tablet of table 1
1. embodiment 1-6 preparation method is as follows：
1) ivermectin, Fenbendazole, praziquantel, PVPP, lactose, micro- is weighed respectively by the above-mentioned parts by weight
Crystalline cellulose, maltodextrin, beef flavor, magnesium stearate, PVP and ethyl-para-hydroxybenzoate.Each raw material that will be weighed
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) Fenbendazole, praziquantel, PVPP, remaining lactose, maltodextrin, crystallite after step 1) is sieved
Ivermectin solid dispersion body prepared by cellulose, beef flavor and step 2) is mixed by the equivalent method of progressively increasing, and is added
Concentration prepared by step 3) is that 3% (w/v) the PVP aqueous solution is mixed in preparing tank, and softwood is made.The softwood energy
Enough hold agglomerating, 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 overly moist
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 ivermectin tablet 1-6.Wherein, the compound ivermectin
The hardness of tablet is 4.5 ± 1kgf.
2. embodiment 7-9 preparation method is as follows：
1) ivermectin, Fenbendazole, praziquantel, PVPP, lactose, hard is weighed respectively by the above-mentioned parts by weight
Fatty acid magnesium 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 bacterium
The ivermectin solid dispersion body of element.
3) PVP after step 1) is sieved is added in purified water, and it is water-soluble to be prepared into the PVP that concentration is 3% (w/v)
Liquid.
4) it is prepared by Fenbendazole, praziquantel, PVPP, remaining lactose and step 2) after step 1) is sieved
Ivermectin solid dispersion body mixed by the equivalent method of progressively increasing, and the concentration for adding step 3) preparation is the poly- of 3% (w/v)
The dimension ketone 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 overly moist
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 ivermectin tablet 7-9.Wherein, the compound ivermectin
The hardness of tablet is 4.5 ± 1kgf.
3. embodiment 10-12 preparation method is as follows：
1) ivermectin, Fenbendazole, praziquantel, PVPP, lactose, ox are weighed respectively by the above-mentioned parts by weight
Meat essence, magnesium stearate, ethyl-para-hydroxybenzoate and PVP.Each raw material weighed is crushed and passed through respectively
The processing of 100 mesh sieves.
2) ivermectin and ethyl-para-hydroxybenzoate are added in absolute ethyl alcohol and are completely dissolved, and add part
Lactose is 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 at
Reason, the ivermectin solid dispersion body containing 1% ivermectin is made.
3) PVP after step 1) is sieved 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 Fenbendazole, praziquantel, PVPP, beef flavor, remaining lactose and
Ivermectin solid dispersion body prepared by step 2) 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 is
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 overly moist
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 ivermectin tablet 10-12.Wherein, compound Yi Wei bacterium
The hardness of plain piece agent is 4.5 ± 1kgf.
Comparative example 1
This comparative example is tablet 1, and the difference of the component and the component of embodiment 7 of comparative example 1 is：With following weight percent
Than weighing each raw material：0.03 part of ivermectin, 20 parts of Fenbendazole, 20 parts of praziquantel, 120 parts of lactose, 20 parts of PVPP,
2 parts of 5 parts of PVP and magnesium stearate.The preparation method of the comparative example 1 is identical with the preparation method of embodiment 7.
Comparative example 2
This comparative example is tablet 2, and the difference of the component and the component of embodiment 7 of comparative example 2 is：It is not added with Fenbendazole
And praziquantel, other components and proportioning are same as Example 7.The preparation method of the comparative example 2 and the preparation method of embodiment 7
It is identical.
Comparative example 3
This comparative example is tablet 3, and the difference of the component and the component of embodiment 7 of comparative example 3 is：It is not added with ivermectin
And praziquantel, other components and proportioning are same as Example 7.The preparation method of the comparative example 3 and the preparation method of embodiment 7
It is identical.
Comparative example 4
This comparative example is tablet 4, and the difference of the component and the component of embodiment 7 of comparative example 4 is：It is not added with ivermectin
And Fenbendazole, other components and proportioning are same as Example 7.The preparation method of the comparative example 4 and the preparation side of embodiment 7
Method is identical.
Comparative example 5
This comparative example is tablet 5, the component of comparative example 5 and the component all same of embodiment 7.Difference is：Its preparation side
Ivermectin is not added in absolute ethyl alcohol in method and is completely dissolved, but by step 1) sieve after Fenbendazole, praziquantel,
Ivermectin, PVPP and lactose are directly mixed, and the PVP water that the concentration for adding preparation is 3% (w/v)
Solution is mixed in preparing tank, and softwood is made.
The dissolution rate test of effete test embodiment 1
6, the compound ivermectin of the preparation of embodiment 7 in the compound ivermectin tablet 1 that respectively prepared by Example 1
6 progress dissolution rates in tablet 5 prepared by 6 in tablet 7,6 in the tablet 1 for preparing of comparative example 1 and comparative example 5
Test, test method：According to dissolution rate and drug release determination method (《Republic of China Veterinary Pharmacopoeia version in 2015》(one) is attached
0931) the second method is carried out for record, and 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 ivermectin tablet 1 and embodiment 7 prepare
Three kinds of composition (Yi Wei of tablet 5 prepared by the tablet 1 and comparative example 5 that compound ivermectin tablet 7 is prepared relative to comparative example 1
Rhzomorph, praziquantel, Fenbendazole) the equal conspicuousness of dissolution rate improve, meet dissolution specification.And tablet 1 prepared by comparative example 1
The dissolution rate of three kinds of compositions (ivermectin, praziquantel, Fenbendazole) is unqualified.
The uniformity of effete test embodiment 2 is tested
The compound Yi Wei bacterium for respectively preparing 10 in compound ivermectin tablet 1 prepared by embodiment 1, embodiment 7
10 progress uniformity tests in tablet 1 prepared by 10 in plain piece agent 7 and comparative example 1, test method：It is equal according to content
Evenness inspection technique (《Republic of China Veterinary Pharmacopoeia version in 2015》(one) annex 0941) carry out, by external standard method with peak area
Calculate the content of every.Test result is as shown in table 3.
The uniformity test result of table 3
Conclusion：It can be seen from the data of table 3, embodiment 1 prepare compound ivermectin tablet 1 and embodiment 7 prepare
The uniformity of dosage units of compound ivermectin tablet 7 is preferable, and its uniformity (A+2.2S) is respectively less than 15, meets uniformity requirements, and phase
The equal conspicuousness of each composition uniformity of the tablet 1 prepared for comparative example 1 improves, and each component content uniformity of comparative example 1
It is unqualified.
The influence factor of embodiment 3 is tested
In order to verify stability of the compound ivermectin tablet under extraordinary environment in the present invention, prepared by Example 1
Compound ivermectin tablet 7 prepared by compound ivermectin tablet 1 and embodiment 7, hot test, intense light irradiation experiment are carried out respectively
And high wet test etc. carries out influence factor experiment, 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, content, dissolution rate to samples taken etc. carry out observation detection, and compared with the result of 0 day, table 4
For compound ivermectin tablet 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 ivermectin tablet prepared by embodiment 1 and embodiment 7 is at 60 DEG C
Every Testing index has no significant change under high temperature, 4500 ± 500lx intense light irradiation and 90% ± 5% high humidity environment, quality
It is relatively stable, meet stability requirement.
The accelerated stability of effete test embodiment 4 is tested
In order to verify the stability of compound ivermectin tablet in the present invention, compound ivermectin prepared by Example 1
Compound ivermectin tablet 7 prepared by tablet 1 and embodiment 7 is appropriate, respectively in 40 ± 2 DEG C of temperature, relative humidity 75% ± 5%
Under conditions of place 6 months and carry out accelerated stability test, 1st month during experiment, 2 months, 3 months, 6 months the end of month point
Do not sample once, observation detection, and the result with 0 day are carried out to the character of samples taken, content, dissolution rate, relevant material etc.
It is compared, test method is according to the pharmaceutical preparation accelerated test side under material medicine and preparation stability test direction principle item
Method (《Republic of China Veterinary Pharmacopoeia (version in 2015)》(one) annex 9001) carry out.Table 5 is compound ivermectin tablet
Accelerated stability test result.
The accelerated stability test result of table 5
Conclusion：It can be seen from table 5 detects data, compound ivermectin tablet prepared by embodiment 1 and embodiment 7 is in temperature
Every Testing index has no significant change under conditions of 40 ± 2 DEG C of degree, relative humidity 75% ± 5%, and quality is relatively stable, meets
Stability requirement.
The efficacy test of effete test embodiment 5
Example 1 prepares compound ivermectin tablet 1, compound ivermectin tablet 7 prepared by embodiment 7 and comparative example
Tablet 1-5 prepared by 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, is judged as parasitic disease dog, and every 10 are included into one group, are respectively
A, B, C, D, E, F, G and H group.A groups press 1/3kg oral administered compound ivermectins tablet 1, and B groups press 1/3kg oral administered compounds Yi Wei
Rhzomorph tablet 7, C groups press tablet 1 prepared by 1/3kg oral contrasts example 1, and D groups press piece prepared by 1/3kg oral contrasts example 2
Agent 2, E groups press tablet 3 prepared by 1/3kg oral contrasts example 3, and F groups press tablet 4 prepared by 1/3kg oral contrasts example 4, G groups
The tablet 5 prepared by 1/3kg oral contrasts example 5, 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, each group excrement sample is gathered respectively within the 10th day, the 15th day
Product 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 line
Worm worm's ovum number } * 100%
Conclusion：The phase of compound ivermectin tablet 7 that the embodiment 1 prepares compound ivermectin tablet 1 and prepared by embodiment 7
It is significantly increased for the comparative example 1-5 tablet 1-5 prepared anthelminthic effect, the especially expeling to whipworm, fluke, tapeworm
Rate performance is good.In addition, during compound ivermectin tablet 1 and compound ivermectin tablet 7 is used, animal does not occur
Obvious uncomfortable reaction.Therefore, ivermectin, Fenbendazole and the praziquantel in the compound ivermectin tablet of the invention
It is compound, preferably collaboration wide spectrum expelling parasite insecticidal effect can be produced, can effectively kill the parasites such as dog nematode, tapeworm, fluke,
The compound ivermectin tablet 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 protection of the present invention
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 ivermectin tablet, it is characterised in that be mainly prepared by each raw material of following parts by weight：Yi Wei bacterium
0.01 part -0.05 part of element, 5 parts -10 parts of Fenbendazole, 2 parts -5 parts of praziquantel, 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 ivermectin tablet according to claim 1, it is characterised in that the also tune including 1 part -4 parts of parts by weight
Taste agent and the preservative of 0.01 part -0.04 part of parts by weight.
3. compound ivermectin tablet according to claim 2, it is characterised in that prepared by each raw material of following parts by weight
Form：0.03 part -0.04 part of ivermectin, 7 parts -8 parts of Fenbendazole, 4 parts -5 parts of praziquantel, 5 parts -8 parts of disintegrant, filler
0.01 part -0.03 part of 70 parts -85 parts, 1 part -2 parts of lubricant, 0.5 part -1 part of adhesive, 1 part -2 parts of flavor enhancement and preservative.
4. according to the compound ivermectin tablet 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 ivermectin tablet 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 ivermectin tablet 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 ivermectin tablet according to claim 6, it is characterised in that the lactose, the microcrystalline cellulose
Mass ratio with the maltodextrin is 60：10：5.
8. according to the compound ivermectin tablet 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 ivermectin tablet, it is characterised in that comprise the following steps：
Ivermectin, Fenbendazole are weighed respectively by any one of the claim 1-8 parts by weight, praziquantel, disintegrant, are filled out
Fill agent, 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；
After the Fenbendazole after sieving, the praziquantel after sieving, the disintegrant after sieving, remaining sieving
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 ivermectin tablet, institute
The hardness for stating compound ivermectin tablet is 1kgf-7kgf.
10. the preparation method of compound ivermectin tablet 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 (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN113476467A (en) * | 2021-07-23 | 2021-10-08 | 湖南伟达科技有限公司 | Albendazole ivermectin disintegrating tablet and preparation method thereof |
| CN115813872A (en) * | 2022-12-27 | 2023-03-21 | 佛山市南海东方澳龙制药有限公司 | Compound ivermectin insect repellent tablet for animals and preparation method thereof |
| CN115844843A (en) * | 2022-12-27 | 2023-03-28 | 佛山市南海东方澳龙制药有限公司 | Multi-unit dispersed insect-repellent sheet and method for producing the same |
| CN115869275A (en) * | 2022-12-27 | 2023-03-31 | 佛山市南海东方澳龙制药有限公司 | Insect expelling tablet for animals and preparation method thereof |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105267230A (en) * | 2015-10-12 | 2016-01-27 | 青岛农业大学 | Compound fenbendazole tablet |
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2017
- 2017-10-31 CN CN201711053064.8A patent/CN107753498A/en active Pending
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105267230A (en) * | 2015-10-12 | 2016-01-27 | 青岛农业大学 | Compound fenbendazole tablet |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN113476467A (en) * | 2021-07-23 | 2021-10-08 | 湖南伟达科技有限公司 | Albendazole ivermectin disintegrating tablet and preparation method thereof |
| CN115813872A (en) * | 2022-12-27 | 2023-03-21 | 佛山市南海东方澳龙制药有限公司 | Compound ivermectin insect repellent tablet for animals and preparation method thereof |
| CN115844843A (en) * | 2022-12-27 | 2023-03-28 | 佛山市南海东方澳龙制药有限公司 | Multi-unit dispersed insect-repellent sheet and method for producing the same |
| CN115869275A (en) * | 2022-12-27 | 2023-03-31 | 佛山市南海东方澳龙制药有限公司 | Insect expelling tablet for animals and preparation method thereof |
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