CN108524460A - Nitenpyram double-layer tablets - Google Patents
Nitenpyram double-layer tablets Download PDFInfo
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- CN108524460A CN108524460A CN201810457467.7A CN201810457467A CN108524460A CN 108524460 A CN108524460 A CN 108524460A CN 201810457467 A CN201810457467 A CN 201810457467A CN 108524460 A CN108524460 A CN 108524460A
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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
- A61K9/2072—Pills, tablets, discs, rods characterised by shape, structure or size; Tablets with holes, special break lines or identification marks; Partially coated tablets; Disintegrating flat shaped forms
- A61K9/2086—Layered tablets, e.g. bilayer tablets; Tablets of the type inert core-active coat
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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
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
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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
- A61K9/28—Dragees; Coated pills or tablets, e.g. with film or compression coating
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P33/00—Antiparasitic agents
- A61P33/14—Ectoparasiticides, e.g. scabicides
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Abstract
The present invention relates to a kind of Nitenpyram double-layer tablets, the Nitenpyram double-layer tablets include Nitenpyram release layer and Nitenpyram controlled release layer；The Nitenpyram release layer includes Nitenpyram and the first excipient；The Nitenpyram controlled release layer includes Nitenpyram and the second excipient.Release layer can discharge rapidly active drug ingredient, and Nitenpyram makes active ingredient that can rapidly enter in body and acts on rapidly, kill dog cat body surface adult flea；Controlled release layer uses osmotic pump controlled-releasing technology, Nitenpyram is wrapped in special construction not soluble in water, by certain speed slow release, coordinate with release layer, obtain continuous, extended drug release time-histories, Nitenpyram is set to extend by the effective content time in medicine body blood, blood medicine curve is more preferable, reduces the probability of the secondary recurrence of flea disease.
Description
Technical field
The present invention relates to anti-parasite medicine technical fields, more particularly to Nitenpyram double-layer tablets.
Background technology
Nitenpyram, nitenpyram are a kind of efficient, wide spectrum, novel nicotinamide insecticides, and the mechanism of action is main
Insect nerve is acted on, there is nerve block effect to the axis synaptic receptor of insect.With remarkable interior suction and osmosis, use
Amount is few, and toxicity is low, and the lasting period is long, the advantages that mammalian safe without poisoning.Nitenpyram active compound is lived in nineteen ninety-five by Japan
Friendly company develops and promotes, and 2000 New Year's gifts come (Elanco US Inc.) and release Nitenpyram piece in the U.S., for treating dog cat
The flea of body surface, thereafter the tablet in 2013 China register, the general star of trade name promise.
Nitenpyram is considered to act on the nervous system of flea, interferes the nerve conduction electric signal of flea, causes to jump
Flea is chronically at excitatory state and final death.Have benefited from the outstanding water solubility of bulk pharmaceutical chemicals, Nitenpyram piece is considered in mouth
Functioned to after taking 15 minutes, 0.5-2 hours blood concentrations reach peak value, and are metabolized rapidly, 90% through urine with original
Medicine form is discharged, and the half-life period of dog is only 4 hours, and cat is 8 hours.
Nitenpyram piece can be used for slaughtering for dog cat body surface flea adult, however fail since it is rapid, it is difficult to completely cut off ring
The superinfection of flea disease caused by the flea of border, the dog cat being exposed in flea environment need medication repeatedly in a short time.
Invention content
Based on this, the present invention provides a kind of Nitenpyram double-layer tablets, has the characteristics that quick, efficacy time length.
A kind of Nitenpyram double-layer tablets, Nitenpyram double-layer tablets include Nitenpyram release layer and Nitenpyram controlled release layer；
Nitenpyram release layer includes Nitenpyram and the first excipient；Nitenpyram controlled release layer includes Nitenpyram and the second figuration
Agent.
Above-mentioned Nitenpyram double-layer tablets, release layer can discharge rapidly active drug ingredient, and Nitenpyram makes active ingredient can
It rapidly enters in body and acts on rapidly, kill dog cat body surface adult flea；Controlled release layer uses controlled-release technology, and Nitenpyram is wrapped up
In in slow-release material, by certain speed slow release, coordinates with release layer, obtain continuous, extended drug release time-histories, make
Nitenpyram is extended by the effective content time in medicine body blood, and blood medicine curve is more preferable, and it is secondary multiple to reduce flea disease
The probability of hair.
The mass ratio of Nitenpyram release layer and the Nitenpyram in Nitenpyram controlled release layer in one of the embodiments,
It is 1: 1-1：30.
The mass ratio of Nitenpyram release layer and the Nitenpyram in Nitenpyram controlled release layer in one of the embodiments,
It is 1:2-1:10.
The mass percentage of the Nitenpyram in Nitenpyram release layer is 1%- in one of the embodiments,
40%, the mass percentage of the Nitenpyram in Nitenpyram controlled release layer is 1%-40%.
Nitenpyram double-layer tablets are structure stacked on top of one another or ectonexine structure, Nitenpyram in one of the embodiments,
Controlled release layer is as label, and Nitenpyram release layer is as surrounding layer.
The first excipient includes adhesive, lubricant, disintegrant and diluent in one of the embodiments,.
The first excipient further includes glidant and/or expelling parasite sterilization auxiliary agent in one of the embodiments,.
The second excipient includes adhesive, lubricant, controlled release agent and diluent in one of the embodiments,.
The second excipient further includes glidant and/or film forming agent in one of the embodiments,.
Nitenpyram double-layer tablets further include stomach dissolution type coating material, stomach dissolution type coating material in one of the embodiments,
It is coated on the periphery of Nitenpyram release layer and Nitenpyram controlled release layer.
Specific implementation mode
It to facilitate the understanding of the present invention, below will be to invention is more fully described.But the present invention can be to be permitted
Mostly different form is realized, however it is not limited to embodiment described herein.Make on the contrary, purpose of providing these embodiments is
It is more thorough and comprehensive to the understanding of the disclosure.
Unless otherwise defined, all of technologies and scientific terms used here by the article and belong to the technical field of the present invention
The normally understood meaning of technical staff is identical.Used term is intended merely to description tool in the description of the invention herein
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
Any and all combinations of the Listed Items of pass.
The test method of actual conditions is not specified in the following example, according to conventional methods and conditions, or says according to commodity
The adjusting of bright book suggestion is selected.Reagents or instruments used without specified manufacturer is that can be obtained by commercially available purchase
Conventional products.
The present invention provides a kind of Nitenpyram double-layer tablets, with Nitenpyram for main effective ingredient, is mainly used for killing dog
Cat body surface flea.
The Nitenpyram double-layer tablets are bilayer tablet configuration, and Nitenpyram double-layer tablets include Nitenpyram release layer and alkene pyridine
Worm amine controlled release layer；Nitenpyram release layer includes Nitenpyram and the first excipient；Nitenpyram controlled release layer includes Nitenpyram
And second excipient.
In one embodiment, the mass ratio of Nitenpyram release layer and the Nitenpyram in Nitenpyram controlled release layer is 1:
1-1:30, such as can be, but it is not limited to 1:1,1:2,1:3,1:4,1:5,1:6,1:7,1:8,1:9,1:10,1:11,1:15,
1:20,1:25 or 1：30 etc..Optionally, the mass ratio of Nitenpyram release layer and the Nitenpyram in Nitenpyram controlled release layer
It is 1:2-1:10.
In one embodiment, the mass percentage of the Nitenpyram in Nitenpyram release layer is 1%-40%, example
It such as can be, but be not limited to 1%, 2%, 3%, 4%, 5%, 10%, 12%, 15%, 18%, 20%, 22%, 25%, 28%,
30%, 35% or 40% etc.；The mass percentage of Nitenpyram in Nitenpyram controlled release layer is 1%-40%, such as can
Think, but is not limited to 1%, 2%, 5%, 7%, 10%, 11%, 12%, 13%, 14%, 15%, 16%, 17%, 18%,
19%, 20%, 21%, 22%, 23%, 24%, 25%, 26%, 27%, 28%, 30%, 32%, 35%, 36% or 40%
Deng.
By controlling the mass content and mass ratio of Nitenpyram release layer and Nitenpyram in Nitenpyram controlled release layer,
Make Nitenpyram fast onset, and drug effect can be kept during the release of Nitenpyram controlled release layer, consolidates Nitenpyram quick-release
The repelling and killing efficacy that layer is brought obtains continuous, extended drug release time-histories, makes Nitenpyram by effective in medicine body blood
The content time is extended, and blood medicine curve is more preferable, reduces the probability of the secondary recurrence of flea disease.
In one embodiment, Nitenpyram double-layer tablets are structure stacked on top of one another, Nitenpyram quick-release layer stackup alkene pyridine worm
Amine controlled release layer.
In one embodiment, Nitenpyram double-layer tablets are ectonexine structure, and Nitenpyram controlled release layer is as label, alkene pyridine
Worm amine release layer discharges first as surrounding layer, release layer, then arrives controlled release layer again.
In one embodiment, the first excipient includes adhesive, lubricant, disintegrant and diluent.
In one embodiment, mass percentage content of each component of the first excipient in Nitenpyram release layer point
It is not：Adhesive 1%-10%, such as can be, but be not limited to 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9% or
10% etc.；Lubricant 1%-3%, such as can be, but it is not limited to 1%, 1.2%, 1.3%, 1.5%, 1.8%, 2%,
2.2%, 2.4%, 2.5%, 2.7%, 2.8% or 3% etc.；Disintegrant 1%-10%, such as can be, but it is not limited to 1%,
2%, 2.5%, 3%, 3.5%, 4%, 4.5%, 5%, 5.5%, 6%, 6.5%, 7%, 7.5%, 8%, 8.5%, 9%,
9.5% or 10% etc.；Diluent surplus, diluent are also known as filler, generally inert substance, are not produced with most of drug
Raw reaction, main function is the weight or volume for filling tablet, in order to preparations shaping and divided dose, consequently facilitating pressure
Piece, dosage depend primarily on the weight or volume of prepared medicament.
Adhesive by fine drug powder wetting, bonding primarily to be made particle in order to tabletting.Adhesive is selected from poly- second
Alkenyl pyrrole lattice alkanone, polyvinylpyrrolidone-vinyl acetate polymer, starch, pregelatinized starch, dextrin, carboxymethyl are fine
Tie up element, ethanol-water mixture, methylcellulose, carboxyrnethyl starch sodium, hydroxypropyl methyl cellulose and one kind in sodium alginate or
It is a variety of.If adhesive can be polyvinyl pyrrole lattice alkanone or polyvinylpyrrolidone-vinyl acetate polymer, or shallow lake
Powder or pregelatinized starch or dextrin or ethanol-water mixture or carboxyrnethyl starch sodium or starch and pregelatinized starch or hydroxypropyl
Ylmethyl cellulose and sodium alginate etc..
Flow improver additive of the lubricant as medicament can improve mobility of particle, improve bulk density, keep tablet obtained hard
Degree increases, and disintegration time limited shortens, to improve drug-eluting speed.Lubricant be selected from talcum powder, stearic acid, silica, firmly
Resin acid calcium, it is one or more in magnesium stearate and atoleine.If lubricant can be talcum powder or stearic acid or dioxy
SiClx or calcium stearate or magnesium stearate or atoleine or talcum powder and stearic mixture or talcum powder and tristearin
The mixture or stearic acid of sour magnesium and the mixture etc. of silica.
Disintegrant refers to that tablet can be made to split the substance for being broken into fine particle rapidly in gastro-intestinal Fluid, to keep active constituent fast
Speed dissolves and absorbs, and plays a role.Disintegrant is selected from starch, sodium carboxymethyl starch, low-substituted hydroxypropyl cellulose, crosslinked polyethylene
It is one or more in pyrrolidones and croscarmellose sodium.As disintegrant can be starch or sodium carboxymethyl starch,
Or low-substituted hydroxypropyl cellulose or crosslinked polyvinylpyrrolidone or croscarmellose sodium or starch and carboxymethyl
Sodium starch or low-substituted hydroxypropyl cellulose and crosslinked polyvinylpyrrolidone or crosslinked polyvinylpyrrolidone and crosslinking carboxylic
Sodium carboxymethylcellulose pyce etc..
Diluent is selected from starch, pregelatinized starch, calcium monohydrogen phosphate, dextrin, microcrystalline cellulose, lactose, mannitol, xylose
It is one or more in alcohol and D-sorbite.If diluent can be starch or pregelatinized starch or calcium monohydrogen phosphate or dextrin,
Or microcrystalline cellulose or lactose or microcrystalline cellulose and lactose or mannitol, xylitol and D-sorbite etc..
In one embodiment, the first excipient further includes glidant and/or expelling parasite sterilization auxiliary agent.Glidant and expelling parasite are killed
Mass percentage of the bacterium auxiliary agent in Nitenpyram release layer be respectively：Glidant 0-3%, such as can be, but be not limited to
0,1%, 1.3%, 1.5%, 1.7%, 1.9%, 2%, 2.2%, 2.5%, 2.7%, 2.9% or 3% etc.；Auxiliary agent is sterilized in expelling parasite
0.5%-2%, such as can be, but it is not limited to 0.5%, 0.8%, 0.9%, 1%, 1.1%, 1.3%, 1.5%, 1.7%,
1.9% or 2% etc..
It may be noted that when, when in excipient simultaneously comprising lubricant and glidant when, lubricant is with glidant in alkene pyridine
Quality total content in worm amine release layer is 1%-3%.
Expelling parasite sterilize auxiliary agent promote preparation bactericidal effect, and to preparation have certain flavored action, for preparation bring compared with
Pleasant smell optimizes user experience.Expelling parasite sterilization auxiliary agent can be, but be not limited to Thymol, carvacrol, eugenol,
It is one or more in carvacrol, linalool, cymol etc..If expelling parasite sterilization auxiliary agent can be Thymol, or perfume
Celery phenol or eugenol or carvacrol or linalool or cymol or Thymol and carvacrol or clove tree
Phenol, carvacrol and linalool etc..
In one embodiment, the second excipient includes adhesive, lubricant, controlled release agent and diluent.
Mass percentage content of each component of second excipient in Nitenpyram controlled release layer be respectively：Adhesive 1%-
10%, such as can be, but it is not limited to 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9% or 10% etc.；Lubricant
1%-3%, such as can be, but it is not limited to 1%, 1.3%, 1.5%, 1.7%, 2%, 2.2%, 2.5%, 2.8% or 3%
Deng；Controlled release agent 20%-65%, such as can be, but it is not limited to 20%, 23%, 25%, 30%, 35%, 37%, 38%,
39%, 40%, 41%, 42%, 43%, 44%, 45%, 50%, 55%, 58%, 60% or 65% etc.；Diluent surplus,
Dosage depends primarily on the weight or volume of prepared medicament and the needs of tablet forming technique.
Adhesive by fine drug powder wetting, bonding primarily to be made particle in order to tabletting.Adhesive is selected from poly- second
Alkenyl pyrrole lattice alkanone, polyvinylpyrrolidone-vinyl acetate polymer, starch, pregelatinized starch, dextrin, carboxymethyl are fine
Tie up element, ethanol-water mixture, methylcellulose, carboxyrnethyl starch sodium, hydroxypropyl methyl cellulose and one kind in sodium alginate or
It is a variety of.If adhesive can be polyvinyl pyrrole lattice alkanone or polyvinylpyrrolidone-vinyl acetate polymer, or shallow lake
Powder or pregelatinized starch or dextrin or ethanol-water mixture or carboxyrnethyl starch sodium or starch and pregelatinized starch or hydroxypropyl
Ylmethyl cellulose and sodium alginate etc..
Flow improver additive of the lubricant as medicament can improve mobility of particle, improve bulk density, keep tablet obtained hard
Degree increases, and disintegration time limited shortens, to improve drug-eluting speed.Lubricant be selected from talcum powder, stearic acid, silica, firmly
Resin acid calcium, it is one or more in magnesium stearate and atoleine.If lubricant can be talcum powder or stearic acid or dioxy
SiClx or calcium stearate or magnesium stearate or atoleine or talcum powder and stearic mixture or talcum powder and tristearin
The mixture or stearic acid of sour magnesium and the mixture etc. of silica.
Controlled release agent is swellable after contacting the liquid with gastro-intestinal Fluid property, constitutes controlled release matrix, and Nitenpyram is wrapped
In interior.The skeleton builds for water insoluble substance, and there are drug concentration gradients between skeleton and gastro-intestinal Fluid, attract skeletal internal alkene
Pyridine worm amine gradually diffuses to outside；The skeleton can have slow corrosion characteristics, discharge drug by slow corrosion；The skeleton or
There can be hydrophilic gel, form gel after meeting water, the rate of release of water soluble drug depends on expansion of the drug by gel layer
Speed is dissipated, and the small drug of solubility in water, rate of release are determined by the gradually corrosion speed of gel layer；The skeleton or simultaneously
With above-mentioned one or more characteristics.
Controlled release agent can be, but be not limited to ethyl cellulose, methacrylate, cellulosic polymer, acrylic resin,
In a few pyrrolidones of polyethylene, guar gum, starch, starch-based polymer, methacrylic acid copolymer, high molecular weight polyvinyl alcohol
It is one or more.Such as controlled release agent can be methacrylate or cellulosic polymer or acrylic resin or poly- second
A few pyrrolidones of alkene or guar gum or starch or starch-based polymer or starch-based polymer and methacrylic acid copolymer,
Or cellulosic polymer and high molecular weight polyvinyl alcohol etc..
Diluent is selected from starch, pregelatinized starch, calcium monohydrogen phosphate, dextrin, microcrystalline cellulose, lactose, mannitol, xylose
It is one or more in alcohol and D-sorbite.If diluent can be starch or pregelatinized starch or calcium monohydrogen phosphate or dextrin,
Or microcrystalline cellulose or lactose or microcrystalline cellulose and lactose or mannitol, xylitol and D-sorbite etc..
In one embodiment, the second excipient further includes glidant and/or film forming agent.
The mass content of glidant and film forming agent in Nitenpyram controlled release layer is respectively：Glidant 0-3%, such as can be with
For, but it is not limited to 0,0.5%, 1%, 1.3%, 1.5%, 1.7%, 2%, 2.2%, 2.5%, 2.8% or 3% etc.；Film forming agent
0.05%-5%, such as can be, but it is not limited to 0.05%, 0.1%, 0.5%, 0.7%, 1%, 1.3%, 1.5%, 1.7%,
1.9%, 2%, 2.5%, 3%, 3.5%, 4%, 4.5% or 5% etc..
Film forming agent can be, but be not limited to ethyl cellulose, hydroxypropyl methyl cellulose, hydroxypropyl cellulose, styrene-
It is one or more in vinylpyridine copolymer, polyvinylpyrrolidone, polyvinyl alcohol, ethylene glycol and acrylic resin etc..Such as
Film forming agent is hydroxypropyl methyl cellulose or hydroxypropyl cellulose or styrene-ethylene pyridine copolymer or polyvinyl pyrrole
Alkanone or polyvinyl alcohol or ethylene glycol and acrylic resin etc..
In some embodiments, film forming agent is grouped as by multiple groups, wherein including pore material, pore material is soluble object
Matter occupies certain space when forming preparation, and arrange in pairs or groups coating material not soluble in water or film forming agent use make film surface shape
At hole, adjustment drug releasing rate.Pore material can be, but be not limited to polyalcohol and its derivative or water soluble polymer
Material, such as pore material can be PEG400, PEG600, PEG1000, PEG1500, hydroxypropyl methyl cellulose, polyethylene
It is one or more in alcohol, urea etc..
The mass ratio that pore material accounts for film forming agent is 5%-50%, such as can be, but is not limited to 5%, 5.5%,
10%, 15%, 20%, 22%, 25%, 28%, 30%, 34%, 35%, 36%, 38%, 40%, 45%, 46% or 50%
Deng.
In one embodiment, Nitenpyram double-layer tablets further include stomach dissolution type coating material, stomach dissolution type coating material cladding
In the periphery of Nitenpyram release layer and Nitenpyram controlled release layer.Quality of the stomach dissolution type coating material in Nitenpyram double-layer tablets
Content is 1%-3%, such as can be, but is not limited to 1%, 1.3%, 1.5%, 1.7%, 2%, 2.2%, 2.5%, 2.8%,
Or 3% etc..
Stomach dissolution type coating material can be, but be not limited to hydroxypropyl methyl cellulose, hydroxypropyl cellulose, styrene-second
Annulated pyridine copolymer, polyvinylpyrrolidone, polyvinyl alcohol, ethylene glycol are one or more in acrylic resin etc..It is such as soluble in the stomach
Type coating material is hydroxypropyl methyl cellulose or hydroxypropyl cellulose or styrene-ethylene pyridine copolymer or polyethylene
Pyrrolidones or polyvinyl alcohol or ethylene glycol or acrylic resin or hydroxypropyl methyl cellulose and hydroxypropyl cellulose, or
Polyvinylpyrrolidone and polyvinyl alcohol etc..
Nitenpyram double-layer tablets of the present invention, release layer can discharge rapidly active drug ingredient, and Nitenpyram makes active ingredient
It can rapidly enter in body and act on rapidly, kill dog cat body surface adult flea；Controlled release layer uses osmotic pump controlled-releasing technology, by alkene pyridine
Worm amine is wrapped in special construction not soluble in water, by certain speed slow release, is coordinated with release layer, is effectively extended alkene pyridine worm
The drug effect of amine obtains quick, the effect of drug effect length.
It is specific embodiment below：
Embodiment 1
The Nitenpyram double-layer tablets of the present embodiment are upper and lower laminated construction, and total tablet weight is 0.35g, wherein Nitenpyram speed
Release synusia weight 150mg, Nitenpyram controlled release synusia weight 200mg.
The mass content of each component is respectively in Nitenpyram release layer：Main ingredient Nitenpyram 6.7% bonds agent carboxymethyl
Sodium cellulosate 5%, disintegrant croscarmellose sodium 3%, glidant silica 2%, magnesium stearate lubricant 1%,
Surplus is filler microcrystalline cellulose 82.3%.
The mass content of each component is respectively in Nitenpyram controlled release layer：Main ingredient Nitenpyram 12.5%, controlled release agent hydroxypropyl
Ylmethyl cellulose 40%, the poly- sodium carboxymethylcellulose 3% of adhesive, glidant silica 2%, magnesium stearate lubricant
1%, surplus is filler microcrystalline cellulose.
Preparation method：
Nitenpyram release layer：In FVZ speed mixer, Nitenpyram is uniformly mixed with microcrystalline cellulose, using appropriate
The carboxymethylcellulose sodium solution of concentration is pelletized, and is dried, screening, and with silica, magnesium stearate, cross-linked carboxymethyl cellulose
Sodium is uniformly mixed, and particle 1 is made.
Nitenpyram controlled release layer：In FVZ speed mixer, by Nitenpyram and microcrystalline cellulose, hydroxypropyl methyl cellulose
Mixing is pelletized using the poly- carboxymethylcellulose sodium solution of appropriate concentration, is dried, screening, and mixed with silica, magnesium stearate
It closes uniformly, particle 2 is made.
It is fed respectively using bi-layer tablet press, particle 1 and particle 2 is pressed into double-layer tablets.
Embodiment 2
The Nitenpyram double-layer tablets of the present embodiment are upper and lower laminated construction, and total tablet weight is 0.5g, wherein Nitenpyram quick-release
Synusia weight 200mg, Nitenpyram controlled release synusia weight 300mg.
The mass content of each component is respectively in Nitenpyram release layer：Main ingredient Nitenpyram 15%, binder starch
5%, disintegrator carboxymethylstarch sodium 2.25%, glidant silica 2%, magnesium stearate lubricant 1%, surplus is filler breast
Sugar 74.75%.
The mass content of each component is respectively in Nitenpyram controlled release layer：Main ingredient Nitenpyram 25%, controlled release agent ethyl are fine
Dimension element 45%, binder starch 5%, glidant talcum powder 2%, magnesium stearate lubricant 1%, surplus are filler lactose
22%.
Preparation method：
Nitenpyram release layer：In FVZ speed mixer, Nitenpyram is uniformly mixed with lactose, carboxyrnethyl starch sodium, profit
It is pelletized, is dried with the starch solution of appropriate concentration, screening, and be uniformly mixed with silica, magnesium stearate, particle 1 is made.
Nitenpyram controlled release layer：In FVZ speed mixer, Nitenpyram and lactose, ethyl cellulose are mixed, using proper
When the starch solution of concentration is pelletized, drying is sieved, and is uniformly mixed with talcum powder, magnesium stearate, and particle 2 is made.
It is fed respectively using bi-layer tablet press, particle 1 and particle 2 is pressed into double-layer tablets.
Embodiment 3
The Nitenpyram double-layer tablets of the present embodiment are ectonexine structure, and total tablet weight is 0.68g, wherein Nitenpyram quick-release
Synusia weight 200mg, Nitenpyram controlled release synusia weight 439.6mg, stomach dissolution type coating material 20.4mg.
The mass content of each component is respectively in Nitenpyram release layer：Main ingredient Nitenpyram 25% bonds agent carboxymethyl
Sodium cellulosate 5%, disintegrant croscarmellose sodium 3%, glidant talcum powder 2%, magnesium stearate lubricant 1% drive
Worm auxiliary agent Thymol 1%, surplus are filler lactose and microcrystalline cellulose, account for 63% altogether.
The mass content of each component is respectively in Nitenpyram controlled release layer：Main ingredient Nitenpyram 27.17%, adhesive carboxylic first
Base sodium cellulosate 5%, controlled release agent hydroxypropyl methyl cellulose 40%, glidant silica 2%, magnesium stearate lubricant 1%,
Surplus be filler lactose, about 23.8%.
Stomach dissolution type coating material acrylic resin accounts for total about 3%.
Preparation method：
Nitenpyram release layer：In FVZ speed mixer, by Nitenpyram and lactose, microcrystalline cellulose, cross-linked carboxymethyl
Sodium cellulosate is uniformly mixed, and is pelletized, is dried using the carboxymethylcellulose sodium solution of appropriate concentration, screening, and with talcum powder, hard
Fatty acid magnesium is uniformly mixed, and particle 1 is made.
Nitenpyram controlled release layer：In FVZ speed mixer, Nitenpyram and lactose, hydroxypropyl methyl cellulose are mixed,
It is pelletized, is dried using the carboxymethylcellulose sodium solution of appropriate concentration, screening, and be uniformly mixed with silica, magnesium stearate,
Particle 2 is made.
It is fed respectively using bi-layer tablet press, particle 1 and particle 2 is pressed into double-layer tablets, and utilize the third of appropriate concentration
Olefin(e) acid resin solution is coated.
Embodiment 4
The Nitenpyram double-layer tablets of the present embodiment are ectonexine structure, and total tablet weight is 0.5g, wherein Nitenpyram release layer
Piece weight 150mg, Nitenpyram controlled release synusia weight 340mg, stomach dissolution type coating material 10mg.
The mass content of each component is respectively in Nitenpyram release layer：Main ingredient Nitenpyram 20%, adhesive pregelatinated
Starch 3%, disintegrant croscarmellose sodium 5%, magnesium stearate lubricant 2.5%, expelling parasite auxiliary agent carvacrol
0.5%, surplus is filler mannitol and microcrystalline cellulose.
The mass content of each component is respectively in Nitenpyram controlled release layer：Main ingredient Nitenpyram 16%, adhesive pregelatinated
Starch 7%, controlled release agent guar gum 35%, glidant silica 1 %, magnesium stearate lubricant 2%, surplus are filler breast
Sugar.
Stomach dissolution type coating material acrylic resin accounts for total about 2%.
Preparation method：
Nitenpyram release layer：In FVZ speed mixer, by Nitenpyram and mannitol, microcrystalline cellulose, Nepeta lavandulacea
Phenol be uniformly mixed, using appropriate concentration pregelatinized starch solution pelletize, dry, screening, and with magnesium stearate, cross-linked carboxymethyl
Sodium cellulosate is uniformly mixed, and particle 1 is made.
Nitenpyram controlled release layer：In FVZ speed mixer, Nitenpyram and lactose, guar gum are mixed, using appropriate dense
The pregelatinized starch solution of degree is pelletized, and is dried, screening, and is uniformly mixed with silica, magnesium stearate, and particle 2 is made.
It is fed respectively using bi-layer tablet press, particle 1 and particle 2 is pressed into double-layer tablets, and utilize the third of appropriate concentration
Olefin(e) acid resin solution is coated.
Embodiment 5
The Nitenpyram double-layer tablets of the present embodiment are upper and lower laminated construction, and total tablet weight is 0.6g, wherein Nitenpyram quick-release
Synusia weight 180mg, Nitenpyram controlled release synusia weight 420mg.
The mass content of each component is respectively in Nitenpyram release layer：Main ingredient Nitenpyram 20%, adhesive dextrin
10%, disintegrant starch 7%, glidant talcum powder 1%, lubricant stearic acid 2%, surplus is filler starch and xylitol.
The mass content of each component is respectively in Nitenpyram controlled release layer：Main ingredient Nitenpyram 20%, controlled release agent cellulose
Polymer 30%, adhesive dextrin 10%, lubricant stearic acid 3%, film forming agent 2%, surplus are filler starch and xylitol；
Wherein, film forming agent is the mixture of ethyl cellulose and polyvinyl alcohol, and polyvinyl alcohol is pore material, accounts for the quality of film forming agent
Ratio is 12%.
Preparation method：
Nitenpyram release layer：In FVZ speed mixer, Nitenpyram is uniformly mixed with starch and xylitol, starch,
It is pelletized, is dried using the dextrin solution of appropriate concentration, screening, and be uniformly mixed with stearic acid, particle 1 is made.
Nitenpyram controlled release layer：In FVZ speed mixer, Nitenpyram and starch, xylitol, cellulosic polymer are mixed
It closes, is pelletized, dried using the dextrin solution of appropriate concentration, screening, and be uniformly mixed with magnesium stearate, particle 2 and tabletting is made,
It is coated afterwards with the mixed solution of the ethyl cellulose of appropriate concentration and polyvinyl alcohol.
Using bi-layer tablet press, the controlled release layer after particle 1 and coating is pressed into double-layer tablets.
Embodiment 6
The Nitenpyram double-layer tablets of the present embodiment are upper and lower laminated construction, and total tablet weight is 0.68g, wherein Nitenpyram speed
Release synusia weight 300mg, Nitenpyram controlled release synusia weight 380mg.
The mass content of each component is respectively in Nitenpyram release layer：Main ingredient Nitenpyram 2%, adhesive polyethylene base
Pyrrolidone/vinyl acetate polymer 6%, disintegrant low-substituted hydroxypropyl cellulose 8%, lubricant talcum powder 3%, expelling parasite
Auxiliary agent eugenol 0.5% is sterilized, surplus is filler starch and D-sorbite.
The mass content of each component is respectively in Nitenpyram controlled release layer：Main ingredient Nitenpyram 10%, controlled release agent cellulose
Polymer 20%, adhesive polyethylene base pyrrolidone/vinyl acetate polymer 4%, lubricant talcum powder 3%, film forming agent
Polyvinyl alcohol 4%, surplus are filler starch and D-sorbite.
Preparation method：
Nitenpyram release layer：In FVZ speed mixer, Nitenpyram is mixed with starch, D-sorbite, eugenol
Uniformly, pelletized, dried using the polyvinylpyrrolidone of appropriate concentration-vinyl acetate polymer solution, screening, and with cunning
Mountain flour and low-substituted hydroxypropyl cellulose are uniformly mixed, and particle 1 is made.
Nitenpyram controlled release layer：In FVZ speed mixer, by Nitenpyram and starch, D-sorbite, cellulosic polymer
Mixing, using appropriate concentration polyvinylpyrrolidone-vinyl acetate polymer solution pelletize, dry, screening, and with cunning
Mountain flour is uniformly mixed, and particle 2 and tabletting is made, and the rear poly-vinyl alcohol solution with suitable concentration is coated.
It is fed respectively using bi-layer tablet press, the controlled release layer after particle 1 and coating is pressed into double-layer tablets.
Embodiment 7
The Nitenpyram double-layer tablets of the present embodiment are ectonexine structure, and total tablet weight is 0.4g, wherein Nitenpyram release layer
Piece weight 150mg, Nitenpyram controlled release synusia weight 246mg, stomach dissolution type coating material 4mg.
The mass content of each component is in Nitenpyram release layer：Main ingredient Nitenpyram 10%, adhesive dextrin 7%, collapses
Agent croscarmellose sodium 4% is solved, lubricating fluid paraffin 2%, expelling parasite auxiliary agent Thymol 2%, surplus is filler
Starch and microcrystalline cellulose.
The mass content of each component is in Nitenpyram controlled release layer：Main ingredient Nitenpyram 18.2%, adhesive dextrin
3.5%, controlled release agent guar gum 27%, film forming agent 3%, lubricating fluid paraffin 2.5%, surplus is that filler starch and crystallite are fine
Dimension element；Wherein, film forming agent is the mixture of hydroxypropyl cellulose and PEG400, and PEG400 is accounted for as pore material in film forming agent
Mass ratio be 8%.
Stomach dissolution type coating material hydroxypropyl cellulose accounts for total about 1%.
Preparation method：
Nitenpyram release layer：In FVZ speed mixer, by Nitenpyram and starch, microcrystalline cellulose, cross-linked carboxymethyl
Sodium cellulosate is uniformly mixed, and is pelletized, is dried using the dextrin ethanol solution of appropriate concentration, screening, and is mixed with atoleine
It is even, particle 1 is made.
Nitenpyram controlled release layer：In FVZ speed mixer, Nitenpyram and starch, microcrystalline cellulose, guar gum are mixed,
It is pelletized, is dried using the dextrin solution of appropriate concentration, screening, and be uniformly mixed with atoleine, particle 2 and tabletting is made, after
It is coated processing with the hydroxypropyl cellulose of appropriate concentration and PEG400 mixed solutions.
It is fed respectively using bi-layer tablet press, the controlled release layer after particle 1 and coating is pressed into double-layer tablets, and using appropriately
The hydroxypropyl cellulose solution of concentration is coated.
Embodiment 8
The Nitenpyram double-layer tablets of the present embodiment are ectonexine structure, and total tablet weight is 0.55g, wherein Nitenpyram quick-release
Synusia weight 220mg, Nitenpyram controlled release synusia weight 314mg, stomach dissolution type coating material 16mg.
The mass content of each component is respectively in Nitenpyram release layer：Main ingredient Nitenpyram 17.8%, the pre- glue of adhesive
Change starch 8%, disintegrant croscarmellose sodium 10%, glidant cornstarch 1%, magnesium stearate lubricant 2%, drive
Worm auxiliary agent carvacrol 0.5%, surplus are filler lactose and microcrystalline cellulose.
The mass content of each component is respectively in Nitenpyram controlled release layer：Main ingredient Nitenpyram 23%, adhesive pregelatinated
Starch 3%, controlled release agent starch-based polymer 42%, glidant cornstarch 1%, magnesium stearate lubricant 2%, surplus are filling
Agent lactose.
Stomach dissolution type coating material sodium alginate accounts for about the 3% of gross mass.
Preparation method：
Nitenpyram release layer：It in FVZ speed mixer, by Nitenpyram and lactose, microcrystalline cellulose, is uniformly mixed, profit
Pelletized, dried with the pregelatinized starch solution of appropriate concentration, screening, and with cornstarch, croscarmellose sodium, tristearin
Sour magnesium is uniformly mixed, and particle 1 is made.
Nitenpyram controlled release layer：In FVZ speed mixer, Nitenpyram and lactose, starch-based polymer are mixed, utilized
The pregelatinized starch solution granulation of appropriate concentration, dries, screening, and be uniformly mixed with cornstarch, magnesium stearate, particle is made
2。
It is fed respectively using bi-layer tablet press, particle 1 and particle 2 is pressed into double-layer tablets, and utilize the sea of appropriate concentration
Solution of sodium alginate is coated.
Release is tested
Using drug intelligence digestion instrument, the Nitenpyram double-layer tablets of embodiment 1-8 are measured with reference to veterinary drug allusion quotation relevant regulations
Release, as a result such as the following table 1.
Table 1
By above-mentioned release test result it is found that the release of the effective ingredient of the Nitenpyram double-layer tablets of embodiment 1 to 8 can
More than for 24 hours, i.e., drug effect duration is more than for 24 hours, and takes effect in 1h.
Effect test
Flea disease is chosen characterized by itch situation and body surface filter out flea adult in Guangdong pet dog breeding base
Natural occurrence dog only 10, weight is suitable, is all male, is equally divided into two groups, is raised respectively in the two natural rings separated
In border.Group 1 feeds common Nitenpyram piece in first day in experiment, thereafter in the 4th hour, the 12nd hour and the 24th hour
Calculate abdomen back flea number；Group 2 is small in the 4th thereafter in the Nitenpyram two-layer release-controlled tablet for testing first day feeding embodiment 2
When, the 12nd hour and the 24th hour calculate abdomen back flea number, as a result such as table 2.
Table 2
| Group | Average flea number (4h) | Average flea number (12h) | Average flea number (for 24 hours) |
| Group 1 | 0 | 0.3 | 1.1 |
| Group 2 | 0 | 0 | 0.2 |
Common Nitenpyram piece can kill body surface flea in a short time, however it is rapid to fail, and can not defend to come from ring
The superinfection in border can find the flea of more new infection in dog body surface after 12 hours.The Nitenpyram of embodiment 2 is double-deck
Piece overcomes Nitenpyram defect itself so that its effect is rapid and lasting, and protection is held due to having both the fast characteristic killed with controlled release
It is 24 hours or more continuous, and to target animals safety, experimental animal has no adverse reaction.
Each technical characteristic of embodiment described above can be combined arbitrarily, to keep description succinct, not to above-mentioned reality
It applies 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, it is all considered to be the range of this specification record.
Several embodiments of the invention above described embodiment only expresses, the description thereof is more specific and detailed, but simultaneously
It cannot therefore be construed as limiting the scope of the patent.It should be pointed out that coming for those of ordinary skill in the art
It says, 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
Range.Therefore, the protection domain of patent of the present invention should be determined by the appended claims.
Claims (10)
1. a kind of Nitenpyram double-layer tablets, which is characterized in that the Nitenpyram double-layer tablets include Nitenpyram release layer and alkene
Pyridine worm amine controlled release layer；The Nitenpyram release layer includes Nitenpyram and the first excipient；The Nitenpyram controlled release layer packet
Include Nitenpyram and the second excipient.
2. Nitenpyram double-layer tablets according to claim 1, which is characterized in that the Nitenpyram release layer and alkene pyridine worm
The mass ratio of Nitenpyram in amine controlled release layer is 1: 1-1：30.
3. Nitenpyram double-layer tablets according to claim 2, which is characterized in that the Nitenpyram release layer and alkene pyridine worm
The mass ratio of Nitenpyram in amine controlled release layer is 1:2-1:10.
4. Nitenpyram double-layer tablets according to any one of claims 1 to 3, which is characterized in that the Nitenpyram quick-release
The mass percentage of Nitenpyram in layer is 1%-40%, the quality hundred of the Nitenpyram in the Nitenpyram controlled release layer
It is 1%-40% to divide content.
5. Nitenpyram double-layer tablets according to any one of claims 1 to 3, which is characterized in that the Nitenpyram is double-deck
Piece is structure stacked on top of one another or ectonexine structure, and the Nitenpyram controlled release layer is made as label, the Nitenpyram release layer
For surrounding layer.
6. Nitenpyram double-layer tablets according to claim 1, which is characterized in that first excipient include adhesive,
Lubricant, disintegrant and diluent.
7. Nitenpyram double-layer tablets according to claim 6, which is characterized in that first excipient further includes glidant
And/or auxiliary agent is sterilized in expelling parasite.
8. Nitenpyram double-layer tablets according to claim 1, which is characterized in that second excipient include adhesive,
Lubricant, controlled release agent and diluent.
9. Nitenpyram double-layer tablets according to claim 8, which is characterized in that second excipient further includes glidant
And/or film forming agent.
10. Nitenpyram double-layer tablets according to claim 1, which is characterized in that the Nitenpyram double-layer tablets further include
Stomach dissolution type coating material, the stomach dissolution type coating material are coated on the outer of the Nitenpyram release layer and Nitenpyram controlled release layer
Week.
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