CN109287627A - A kind of solid dispersions matrix and its application - Google Patents
A kind of solid dispersions matrix and its application Download PDFInfo
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- CN109287627A CN109287627A CN201811060689.1A CN201811060689A CN109287627A CN 109287627 A CN109287627 A CN 109287627A CN 201811060689 A CN201811060689 A CN 201811060689A CN 109287627 A CN109287627 A CN 109287627A
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- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
- A01N25/00—Biocides, pest repellants or attractants, or plant growth regulators, characterised by their forms, or by their non-active ingredients or by their methods of application, e.g. seed treatment or sequential application; Substances for reducing the noxious effect of the active ingredients to organisms other than pests
- A01N25/08—Biocides, pest repellants or attractants, or plant growth regulators, characterised by their forms, or by their non-active ingredients or by their methods of application, e.g. seed treatment or sequential application; Substances for reducing the noxious effect of the active ingredients to organisms other than pests containing solids as carriers or diluents
- A01N25/10—Macromolecular compounds
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- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
- A01N25/00—Biocides, pest repellants or attractants, or plant growth regulators, characterised by their forms, or by their non-active ingredients or by their methods of application, e.g. seed treatment or sequential application; Substances for reducing the noxious effect of the active ingredients to organisms other than pests
- A01N25/12—Powders or granules
-
- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
- A01N25/00—Biocides, pest repellants or attractants, or plant growth regulators, characterised by their forms, or by their non-active ingredients or by their methods of application, e.g. seed treatment or sequential application; Substances for reducing the noxious effect of the active ingredients to organisms other than pests
- A01N25/12—Powders or granules
- A01N25/14—Powders or granules wettable
-
- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
- A01N25/00—Biocides, pest repellants or attractants, or plant growth regulators, characterised by their forms, or by their non-active ingredients or by their methods of application, e.g. seed treatment or sequential application; Substances for reducing the noxious effect of the active ingredients to organisms other than pests
- A01N25/34—Shaped forms, e.g. sheets, not provided for in any other sub-group of this main group
-
- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
- A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
- A01N43/64—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with three nitrogen atoms as the only ring hetero atoms
- A01N43/647—Triazoles; Hydrogenated triazoles
- A01N43/653—1,2,4-Triazoles; Hydrogenated 1,2,4-triazoles
-
- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
- A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
- A01N43/90—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having two or more relevant hetero rings, condensed among themselves or with a common carbocyclic ring system
-
- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
- A01N47/00—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom not being member of a ring and having no bond to a carbon or hydrogen atom, e.g. derivatives of carbonic acid
- A01N47/08—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom not being member of a ring and having no bond to a carbon or hydrogen atom, e.g. derivatives of carbonic acid the carbon atom having one or more single bonds to nitrogen atoms
- A01N47/10—Carbamic acid derivatives, i.e. containing the group —O—CO—N<; Thio analogues thereof
- A01N47/18—Carbamic acid derivatives, i.e. containing the group —O—CO—N<; Thio analogues thereof containing a —O—CO—N< group, or a thio analogue thereof, directly attached to a heterocyclic or cycloaliphatic ring
-
- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
- A01N51/00—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds having the sequences of atoms O—N—S, X—O—S, N—N—S, O—N—N or O-halogen, regardless of the number of bonds each atom has and with no atom of these sequences forming part of a heterocyclic ring
Abstract
The invention belongs to solid dispersion technology fields, more particularly to a kind of solid dispersions matrix and its application, the eutectic system that the solid dispersions matrix is made of hydrogen-bond donor, hydrogen bond receptor and excipient, the hydrogen-bond donor are any one or a few in glucose, mannitol, citric acid, succinic acid and menthol；The hydrogen bond receptor is choline chloride；The excipient is any one or a few in PEG, PVP and poloxamer.The invention has the benefit that availability is greatly improved firstly, improving the dissolution of property drug hard to tolerate in water；Secondly, pill, water dispersible granules or wettable powder simple process are prepared as solid dispersions matrix using eutectic system, it is easily operated, and poisonous and hazardous organic solvent is not used, it is pollution-free, it is suitable for industrialization production.Furthermore the addition of excipient improves the storage-stable of preparation gained drug, and moisture-sensitive does not liquefy.
Description
Technical field
The invention belongs to solid dispersion technology fields, and in particular to a kind of solid dispersions matrix and its application.
Background technique
After eutectic phenomenon refers to the mixing of two or more drug, there is the phenomenon that soaking or liquefying, eutectic
The fusing point of system is substantially less than the fusing point of any component.As a kind of novel green solvent, there is eutectic solvent steam to force down,
The unique physicochemical properties such as non-toxic, biodegradable, dissolubility and excellent conductivity, electrochemical stability window are wide, and
And its performance can be adjusted by selecting suitable composition and proportion, there is tempting application prospect in many fields.This
Invention mainly utilizes the solubilizing effect of eutectic system, so that drug and eutectic system is generated hydrogen bond action mutually, reaching makes medicine
Object is fully dispersed and then increases the purpose dissolved out in its water.
Solid dispersions refer to a kind of existing point in solid form for being highly dispersed in drug and being formed in solid carrier
The system of dissipating.The partial size of drug in the carrier is mainly used for accelerating and increasing the molten of insoluble drug between 0.001~0.1mm
Out, its bioavilability is improved.What solid dispersions were more was applied to the aspect of indissoluble medicine solubilising, present solid dispersion in the past
The new direction of body research is the sustained release performance for increasing drug.
Choline chloride is the choline for being currently the most frequently used most economical artificial synthesized form, it is mainly used for additive and is mixed into
In the feed of animal, the weight gain such as ovary fecund egg, farrowing and poultry, fish can be stimulated.It or a kind of Plant Light cooperation simultaneously
With promotor, had obvious effects on to yield is increased.The present invention mainly using choline chloride as hydrogen bond receptor, respectively with grape
Sugar, mannitol, citric acid, succinic acid, menthol etc. form eutectic system, for dispersing insoluble medicine.In the present invention, chlorine
Change choline as hydrogen bond receptor and form eutectic system from different hydrogen-bond donors, achievees the effect that disperse drug.With other hydrogen
Key receptor is compared, and choline chloride has certain help to plant growth, and as common additive, security performance has been obtained
Approve.
Polyethylene glycol (polyethylene glycol PEG) is that a kind of to prepare insoluble drug solid dispersion useful
Matrix, advantage essentially consist in: the molecular weight of organic drug is lower than 400 or 500 mostly, and molecular weight polyethylene glycol be 1500,
4000 and 6000, thus chromic fibrous solid solution can be formed.And its fusing point low (55~60 DEG C) is easy to process.In the present invention,
PEG is mainly used for stablizing the property of material, improves the strong absorptive of material, while playing the role of adjusting material solution viscosity.
Insoluble drug at present, such as the main dosage form of avermectin is missible oil or by drug micronization.Missible oil is made
A large amount of organic solvent is needed, it is unfavorable to environment, and drug micronization rear surface free energy is larger, there is becoming for self-assemble
Standard is not achieved in gesture, partial size always, reduces crushing effect.Have at present and disperses insoluble medicine in using choline chloride as hydrogen bond
The technology of the eutectic system of receptor, but the system easy to absorb moisture, the material of solid forms will appear liquid after placing a period of time
Change phenomenon, and merely using PEG as solid dispersions matrix, solution rate is slow in water, and the high molecular material of high-content is easy
Cause solution viscosity excessively high.By PEG in conjunction with eutectic system, the solid dispersions of preparation have polymolecularity and hang the present invention
Buoyancy, production process do not use poisonous and hazardous organic solvent, are suitable for industrialized production.
Summary of the invention
In view of the deficiencies of the prior art, it is an object of the present invention to provide a kind of solid dispersions matrix, to improve slightly solubility
Drug, such as the dissolution rate of slightly solubility pesticide in water.In order to achieve the above-mentioned object of the invention, inventor has carried out many experiments work
Make, discovery, which is utilized, can highly mix dispersion indissoluble by excipient such as the eutectic system combination PEG of hydrogen bond receptor of choline chloride
Property pesticide, increases its dissolution in water.
The technical solution adopted by the present invention to solve the technical problems is:
A kind of solid dispersions matrix, the solid dispersions matrix are by hydrogen-bond donor, hydrogen bond receptor and excipient group
At eutectic system, the hydrogen-bond donor be glucose, mannitol, citric acid, succinic acid and menthol in any one
Or it is several；The hydrogen bond receptor is choline chloride；The excipient be PEG, PVP and poloxamer in any one or it is several
Kind.
Preferably, the mass percentage of the hydrogen-bond donor is 20~60%, the quality percentage of the hydrogen bond receptor
Content is 5~30%, and the mass percentage of the excipient is 10~70%.
The present invention also provides a kind of application of solid dispersions matrix in raising insoluble drug in water dissolution rate.
Preferably, the difficult soluble pesticide of insoluble drug, specially avermectin, Tebuconazole, carbendazim, pyrrole worm
Quinoline, Natamycin or gamma cyhalothrin etc..
Preferably, the slightly solubility pesticide and the mass ratio of the solid dispersions matrix are (1~10): (90~
99)。
Preferably, water dispersible granules, wettable powder or drop is made in the solid dispersions matrix and slightly solubility pesticide
Pill.
The water dispersible granules the preparation method is as follows:
S1: hydrogen-bond donor, hydrogen bond receptor, excipient and slightly solubility pesticide are quantitatively weighed；
S2: raw material weighed in S1 is crushed, and it is spare to cross 60~80 meshes；
S3: by smashed hydrogen-bond donor, hydrogen bond receptor and excipient mix, be heated with stirring in 60~80 DEG C system at
Uniform liquid eutectic system；
S4: slightly solubility pesticide is added slowly in the eutectic system in step S3, continue in 60~80 DEG C stirring 2~
3h, until the system is poured into evaporating dish, is taken out after -20 DEG C of freezing 2h after insoluble drug is fully dispersed in the system,
Obtain solid dispersions；
S5: taking the solid dispersions in S4, and appropriate dispersing agent is added and carries out dry granulation, and whole grain crosses 20~40 meshes,
Grain is in 50~60 DEG C of water dispersible granules obtained by drying.
The wettable powder the preparation method is as follows:
S1: hydrogen-bond donor, hydrogen bond receptor, excipient and slightly solubility pesticide are quantitatively weighed；
S2: raw material weighed in S1 is crushed, and it is spare to cross 60~80 meshes；
S3: by smashed hydrogen-bond donor, hydrogen bond receptor and excipient mix, be heated with stirring in 60~80 DEG C system at
Uniform liquid eutectic system；
S4: slightly solubility pesticide is added slowly in the eutectic system in step S3, continue in 60~80 DEG C stirring 2~
3h, until the system is poured into evaporating dish, is taken out after -20 DEG C of freezing 2h after slightly solubility pesticide is fully dispersed in the system,
Obtain solid dispersions；
S5: appropriate dispersing agent being added in the solid dispersions of step S4 and crosses 250~400 meshes after air-flow crushing, in
50~60 DEG C of wettable powders obtained by drying；
The pill the preparation method is as follows:
S1: hydrogen-bond donor, hydrogen bond receptor, excipient and slightly solubility pesticide are quantitatively weighed；
S2: raw material weighed in S1 is crushed, and it is spare to cross 60~80 meshes；
S3: smashed hydrogen-bond donor, hydrogen bond receptor and excipient being mixed, are placed in pill dripping machine melting tank, in 60~
80 DEG C are heated with stirring to system into uniform liquid eutectic system；
S4: slightly solubility pesticide is added slowly in the eutectic system in step S3, continue in 60~80 DEG C stirring 2~
3h, until slightly solubility pesticide is fully dispersed in the system；
S5: the material in S4 being instilled in condensate liquid and forms dripping pill, separates condensate liquid, is got rid of oil up to pill.
It is compared with the traditional method, the present invention has following prominent the utility model has the advantages that solid disperse matrix provided by the invention
The eutectic system being made of hydrogen-bond donor, hydrogen bond receptor and excipient, is made water dispersible granules with slightly solubility pesticide or can
Wet powder can increase the dissolution rate of insoluble drug in water, to improve the bioavilability of drug.Secondly, using low total
Melt system prepares water dispersible granules, wettable powder or pill simple process as solid dispersions matrix, easily operated, and
It is pollution-free without using poisonous and hazardous organic solvent.Furthermore the addition of excipient improves the storage-stable of preparation gained drug
Property, moisture-sensitive does not liquefy.Finally, there are also certain increasings to slightly solubility pesticide for the hydrogen-bond donor, hydrogen bond receptor and the excipient that are added
Effect, facilitation, further increase the bioavilability of slightly solubility pesticide.
Detailed description of the invention
Attached drawing 1 is embodiment 1, embodiment 2, embodiment 3 and comparative example 1, comparative example 2 prepares resulting water dispersible granules
In, the HPLC spectrogram of the result of extraction of effective component avermectin in water.
Specific embodiment
Below by specific embodiment, technical scheme of the present invention will be further explained in detail.
Embodiment 1
Solid dispersions using eutectic system as matrix are made of the raw material of following parts by weight: Avermectin 100g, moor Lip river
Husky 188 225g of nurse, choline chloride 180g, glucose 495g.
Embodiment 2
Solid dispersions using eutectic system as matrix are made of the raw material of following parts by weight: Avermectin 100g,
PEG6000 180g, choline chloride 252g, succinic acid 268g and mannitol 200g.
Embodiment 3
Solid dispersions using eutectic system as matrix are made of the raw material of following parts by weight: Avermectin 100g,
PVP500g, choline chloride 80g, mannitol 320g.
Embodiment 4
Solid dispersions using eutectic system as matrix are made of the raw material of following parts by weight: imidacloprid 100g,
PEG4000 100g, PVP 98g, choline chloride 225g and menthol 477g.
Embodiment 5
Solid dispersions using eutectic system as matrix are made of the raw material of following parts by weight: Tebuconazole 100g,
PEG6000 216g, choline chloride 162g, mannitol 322g and citric acid 200g.
Embodiment 6
Solid dispersions using eutectic system as matrix are made of the raw material of following parts by weight: carbendazim 80g, PVP
150g, poloxamer 80g, choline chloride 184g, glucose 210g and mannitol 296g.
Embodiment 7
Solid dispersions using eutectic system as matrix are made of the raw material of following parts by weight: Natamycin 70g,
PEG6000 241.8g, choline chloride 167.4g, mannitol 180g, succinic acid 265.4g and menthol 75.4g.
Embodiment 8
In the embodiment of the present invention 1~7 solid dispersions be prepared into water dispersible granules method it is as follows:
S1: hydrogen-bond donor, hydrogen bond receptor, excipient and slightly solubility pesticide are quantitatively weighed；
S2: raw material weighed in S1 is crushed, and it is spare to cross 60~80 meshes；
S3: by smashed hydrogen-bond donor, hydrogen bond receptor and excipient mix, be heated with stirring in 60~80 DEG C system at
Uniform liquid eutectic system；
S4: slightly solubility pesticide is added slowly in the eutectic system in step S3, continue in 60~80 DEG C stirring 2~
3h, until the system is poured into evaporating dish, is taken out after -20 DEG C of freezing 2h after insoluble drug is fully dispersed in the system,
Obtain solid dispersions；
S5: taking the solid dispersions in S4, and appropriate dispersing agent is added and carries out dry granulation, arranged 20~40 meshes,
Grain is in 50~60 DEG C of water dispersible granules obtained by drying.Embodiment 9
In the embodiment of the present invention 1~7 solid dispersions be prepared into wettable powder method it is as follows:
S1: hydrogen-bond donor, hydrogen bond receptor, excipient and slightly solubility pesticide are quantitatively weighed；
S2: raw material weighed in S1 is crushed, and it is spare to cross 60~80 meshes；
S3: by smashed hydrogen-bond donor, hydrogen bond receptor and excipient mix, be heated with stirring in 60~80 DEG C system at
Uniform liquid eutectic system；
S4: slightly solubility pesticide is added slowly in the eutectic system in step S3, continue in 60~80 DEG C stirring 2~
3h, until the system is poured into evaporating dish, is taken out after -20 DEG C of freezing 2h after slightly solubility pesticide is fully dispersed in the system,
Obtain solid dispersions；
S5: appropriate dispersing agent being added in the solid dispersions of step S4 and crosses 250~400 meshes after air-flow crushing, in
50~60 DEG C of wettable powders obtained by drying；
Embodiment 10
In the embodiment of the present invention 1~7 solid dispersions be prepared into pill method it is as follows:
S1: hydrogen-bond donor, hydrogen bond receptor, excipient and slightly solubility pesticide are quantitatively weighed；
S2: raw material weighed in S1 is crushed, and it is spare to cross 60~80 meshes；
S3: smashed hydrogen-bond donor, hydrogen bond receptor and excipient being mixed, are placed in pill dripping machine melting tank, in 60~
80 DEG C are heated with stirring to system into uniform liquid eutectic system；
S4: slightly solubility pesticide is added slowly in the eutectic system in step S3, continue in 60~80 DEG C stirring 2~
3h, until slightly solubility pesticide is fully dispersed in the system；
S5: the material in S4 being instilled in condensate liquid and forms dripping pill, separates condensate liquid, is got rid of oil up to pill.
Comparative example 1
Solid dispersions using eutectic system as matrix are made of the raw material of following parts by weight: Avermectin 100g,
PEG6000 is 900g.
Comparative example 2
Solid dispersions using eutectic system as matrix are made of the raw material of following parts by weight: Avermectin 100g, chlorination
Choline 550g, mannitol 340g.
The solid dispersions of comparative example 1 and comparative example 2 are prepared into the preparation method of water dispersible granules with above-described embodiment 8.
Water dispersible granules are prepared into avermectin in embodiment 1, embodiment 2 and embodiment 3, with comparative example 1 and comparison
Example 2 prepares resulting water dispersible granules and is compared, and evaluates the solubilizing effect of slightly solubility pesticide avermectin.
Embodiment 1, embodiment 2 and embodiment 3 and comparative example 1, comparative example 2 prepare resulting water dispersible granules, effectively
The result of extraction of ingredient avermectin in water carries out evaluation identification using HPLC method, selects ODS C18 chromatographic column, and mobile phase is
Methanol: water=80:20, ultraviolet detection wavelength are 245nm, flow velocity 1ml/min.
The specific method is as follows:
Control group: taking 1g the former medicine of AVM to add 100ml water, 20min is stirred in 300r/min on magnetic stirring apparatus, through micro-
20 μm of sample introductions of filtrate are taken after the membrane filtration of hole.
Experimental group (including embodiment 1,2,3 and comparative example 1,2): water dispersible granules of the 10g containing avermectin are taken to be added
In 100ml water, 20min is stirred in 300r/min on magnetic stirring apparatus, 20 μ l sample introduction of filtrate is taken after filtering with microporous membrane.
Attached drawing 1: embodiment 1, embodiment 2, embodiment 3 and comparative example 1, comparative example 2 are prepared in resulting water dispersible granules,
The HPLC spectrogram of the result of extraction of effective component avermectin in water.
With the B of avermectin1A is as comparison peak, avermectin B in six groups of experiments1The retention time and peak area at the peak a are such as
Shown in table 1.
Table 1:
The above test effect show embodiment 1, in embodiment 2 and embodiment 3 avermectin B1A peak area is larger, because
This using the solid dispersions matrix that is made of hydrogen-bond donor, choline chloride and excipient prepare in resulting water dispersible granules Ah
It is preferable to tie up result of extraction of the rhzomorph in 20min.It is (the control of simple avermectin that avermectin dissolves out in water in embodiment 1
Group) dissolve out in water 6.82 times；It is that prior art avermectin only exists using PEG as solid dispersions matrix (comparative example 1)
4.40 times dissolved out in water.
Avermectin is prepared into the stability analysis of water dispersible granules.
Appropriate embodiment 1 is taken, is placed in 54 DEG C of baking ovens after storing 14 days, investigates water content, the active constituent content of material,
Sieving rate, dissolution rate.
Moisture determination method: karl Fischer-coulometric titration instrumental measurement in GB/T 1600-2001.
Active constituent content: taking suitable sample that quantitative methanol dissolution is added, do external standard with avermectin standard items,
Compare peak area by HPLC method, calculates avermectin content.HPLC condition: ODS C18Chromatographic column, mobile phase are methanol: water=
80:20, ultraviolet detection wavelength are 245nm, flow velocity 1ml/min.
Dispersibility: 9g sample (m is taken1) 900ml distilled water, the stirring and dissolving 1min under the conditions of 300r/min is added.Then
1min is stood, claims solid after the solution of lower layer 1/10 boils off moisture with the solution that vacuum pump draws upper layer 9/10
Shape object weight m2。
Sieving rate: taking weight is m0Sample on vibrating sieving machine, measurement can pass through 20 mesh and be trapped on 40 mesh screens
The weight of particle is m1, sieving rate=m1/m0。
The amount of dissolution measures in aqueous solution:
(1) preparation of external standard: 1. taking 1g avermectin standard items in 50ml volumetric flask, and anhydrous methanol constant volume is added simultaneously
Ultrasonic dissolution；2. taking 1ml solution in 20ml volumetric flask from above-mentioned volumetric flask, distilled water constant volume is added；3. taking 20 μ l above-mentioned
Acquired solution takes, with HPLC (ODS C18Chromatographic column, mobile phase are methanol: water=80:20, and ultraviolet detection wavelength is 245nm, stream
Speed measures the peak area A of external standard for 1ml/min)1；
(2) processing of sample to be tested: 1g avermectin solid dispersions are taken to be added in 100ml water, on magnetic stirring apparatus
300r/min stirs 20min, 20 μ l sample introduction of filtrate is taken after filtering with microporous membrane, HPLC condition is identical with (2), measures sample
Peak area be A2, C2=A2×C1/A1(C1=1mg/ml)；
(3)
Concrete outcome is shown in Table 2.
Table 2:
The above test effect shows the eutectic system being made of hydrogen-bond donor, choline chloride and excipient as solid
Dispersion matrix is compared with simple choline chloride+hydrogen-bond donor composition solid dispersions matrix (comparative example 2), by 14d
After accelerated test, 1,2,3 water content of embodiment, sieving rate is high, illustrates that solid dispersions matrix stability of the invention is good, moisture absorption
Property is weak, is able to maintain the good appearance form of particle；Because PEG content height is so its water content after 14d accelerated test in comparative example 1
It is low, but its solution rate is slow, and standard is not achieved in dispersibility.1,2,3 the amount of dissolution of embodiment is high, and it is (right with simple PEG group matter to illustrate
Ratio 1) it is compared with simple choline chloride+hydrogen-bond donor composition solid dispersions matrix (comparative example 2), solid of the invention
Dispersion matrix can be such that the dissolution rate of avermectin in water greatly increases.
Avermectin is prepared into the evaluating drug effect of water dispersible granules.
This experiment is mainly inquired into the water dispersible granules containing 10% avermectin and is tested to the field efficacy of wild cabbage plutella xylostella.
Experiment sets 4 groups of processing: 1. avermectin effective component 4.50g/hm altogether2；2. avermectin effective component 6.75g/
hm2；3. avermectin effective component 9.00g/hm2；4. blank control.For above 1. -3. in three various concentrations, set respectively
Set embodiment 1,2,3 and comparative example 1,2 five experiment.Every group of experiment is a cell, is repeated 3 times test, totally 48 cells, often
A plot area is 50m2, minizone random alignment.
Experiment place is located at experimental plot at the county Long You of Quzhou City one, is 3335m for examination field area2, soil regime is consistent, examination
Without rainfall during testing.Every 667m2Experimental plot water 45kg, 5 points of samplings of diagonal line before every piece of region is administered, every fixed 5 plants of investigation
Diamondback moth insect population, the 3rd, 7d tune difference diamondback moth worm insect population number living, calculates each cell Revision insect recluced rate and control efficiency after medicine.
(CK is blank group Revision insect recluced rate in formula, and PT is application
Area's Revision insect recluced rate.)
The results are shown in Table 3 for specific experiment:
Table 3:
The above test effect shows under avermectin effective concentration unanimous circumstances, in the embodiment 1,2,3 in the present invention
Revision insect recluced rate and control rate are above the prior art (comparative example 1)；Therefore, embodiment and comparative example Revision insect recluced rate phase to be made
Together, avermectin effective dose needed for embodiment is lower, and the bioavilability of avermectin is improved.
In conclusion the eutectic system conduct provided by the invention being made of hydrogen-bond donor, choline chloride and excipient
Solid dispersions matrix is being prepared into water dispersible granules, wettable for improving application of the slightly solubility pesticide in water in dissolution rate
Property pulvis or pill simple process, it is and environmentally friendly, moreover it is possible to significantly improve the dissolution of slightly solubility pesticide in water, improve
The bioavilability of pesticide reduces the usage amount of pesticide, has very big use value in agricultural production.
Above-mentioned embodiment is only a preferred solution of the present invention, not the present invention is made in any form
Limitation, there are also other variations and modifications on the premise of not exceeding the technical scheme recorded in the claims.
Claims (10)
1. a kind of solid dispersions matrix, which is characterized in that the solid dispersions matrix be by hydrogen-bond donor, hydrogen bond receptor and
The eutectic system of excipient composition, the hydrogen-bond donor are in glucose, mannitol, citric acid, succinic acid and menthol
Any one or a few；The hydrogen bond receptor is choline chloride；The excipient is any one in PEG, PVP and poloxamer
Kind is several.
2. solid dispersions matrix according to claim 1, which is characterized in that the mass percentage of the hydrogen-bond donor is
20~60%, the mass percentage of the hydrogen bond receptor is 5~30%, the mass percentage of the excipient is 10~
70%.
3. a kind of application of solid dispersions matrix as claimed in claim 1 or 2 in raising insoluble drug in water dissolution rate.
4. application of the solid dispersions matrix in raising insoluble drug in water dissolution rate according to claim 3,
It is characterized in that, the difficult soluble pesticide of insoluble drug.
5. application of the solid dispersions matrix in raising insoluble drug in water dissolution rate according to claim 4,
It is characterized in that, the slightly solubility pesticide is avermectin, Tebuconazole, carbendazim, imidacloprid, Natamycin or efficient cyhalothrin
Ester.
6. application of the solid dispersions matrix in raising insoluble drug in water dissolution rate according to claim 5,
It is characterized in that, the mass ratio of the slightly solubility pesticide and the solid dispersions matrix is (1~10): (90~99).
7. application of the solid dispersions matrix in raising insoluble drug in water dissolution rate according to claim 6,
It is characterized in that, water dispersible granules, wettable powder or pill is made in the solid dispersions matrix and slightly solubility pesticide.
8. application of the solid dispersions matrix in raising insoluble drug in water dissolution rate according to claim 7,
It is characterized in that, the solid dispersions matrix and the method that slightly solubility pesticide is prepared into water dispersible granules are as follows:
S1: hydrogen-bond donor, hydrogen bond receptor, excipient and slightly solubility pesticide are quantitatively weighed；
S2: raw material weighed in S1 is crushed, and it is spare to cross 60~80 meshes；
S3: smashed hydrogen-bond donor, hydrogen bond receptor and excipient are mixed, are heated with stirring to system at uniform in 60~80 DEG C
Liquid eutectic system；
S4: slightly solubility pesticide is added slowly in the eutectic system in step S3, continues 2~3h of stirring in 60~80 DEG C,
Until taken out after the system mixture is placed in -20 DEG C of freezing 2h after insoluble drug is fully dispersed in the system, consolidate
Body dispersion；
S5: taking the solid dispersions in S4, and appropriate dispersing agent is added and pelletizes, and whole grain crosses 20~40 meshes, particle in 50~
60 DEG C of water dispersible granules obtained by drying.
9. application of the solid dispersions matrix in raising insoluble drug in water dissolution rate according to claim 7,
It is characterized in that, the solid dispersions matrix and the method that slightly solubility pesticide prepares wettable powder are as follows:
S1: hydrogen-bond donor, hydrogen bond receptor, excipient and slightly solubility pesticide are quantitatively weighed；
S2: raw material weighed in S1 is crushed, and it is spare to cross 60~80 meshes；
S3: smashed hydrogen-bond donor, hydrogen bond receptor and excipient are mixed, are heated with stirring to system at uniform in 60~80 DEG C
Liquid eutectic system；
S4: slightly solubility pesticide is added slowly in the eutectic system in step S3, continues 2~3h of stirring in 60~80 DEG C,
Until being taken out after the system mixture will be placed in -20 DEG C of freezing 2h after slightly solubility pesticide is fully dispersed in the system, obtain
Solid dispersions；
S5: appropriate dispersing agent being added in the solid dispersions of step S4 and crosses 250~400 meshes after air-flow crushing, in 50~
60 DEG C of wettable powders obtained by drying.
10. application of the solid dispersions matrix in raising insoluble drug in water dissolution rate according to claim 7,
It is characterized in that, the solid dispersions matrix and the method that slightly solubility pesticide prepares pill are as follows:
S1: hydrogen-bond donor, hydrogen bond receptor, excipient and slightly solubility pesticide are quantitatively weighed；
S2: raw material weighed in S1 is crushed, and it is spare to cross 60~80 meshes；
S3: smashed hydrogen-bond donor, hydrogen bond receptor and excipient are mixed, are placed in pill dripping machine melting tank, in 60~80 DEG C
System is heated with stirring into uniform liquid eutectic system；
S4: slightly solubility pesticide is added slowly in the eutectic system in step S3, continues 2~3h of stirring in 60~80 DEG C,
Until slightly solubility pesticide is fully dispersed in the system；
S5: the material in S4 being instilled in condensate liquid and forms dripping pill, separates condensate liquid, is got rid of oil up to pill.
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Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110575439A (en) * | 2019-08-15 | 2019-12-17 | 浙江工业大学 | Construction method of macromolecule/eutectic emulsion and application of macromolecule/eutectic emulsion in solubilization of flavonoid drugs |
| CN110639020A (en) * | 2019-08-15 | 2020-01-03 | 浙江工业大学 | Solid dispersion matrix and preparation method and application thereof |
| CN111034718A (en) * | 2019-12-20 | 2020-04-21 | 中国农业大学 | Liquid pesticide preparation and preparation method thereof |
| CN113768871A (en) * | 2021-09-23 | 2021-12-10 | 陕西中医药大学 | Traditional Chinese medicine preparation of hydroxyl carthamin yellow A |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20160143848A1 (en) * | 2014-11-25 | 2016-05-26 | Massachusetts Institute Of Technology | Neat liquid pharmaceutical formulations |
| CN108186575A (en) * | 2018-03-14 | 2018-06-22 | 安徽工业大学 | It is a kind of based on eutectic solvent be solvent embedding system |
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2018
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Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20160143848A1 (en) * | 2014-11-25 | 2016-05-26 | Massachusetts Institute Of Technology | Neat liquid pharmaceutical formulations |
| CN108186575A (en) * | 2018-03-14 | 2018-06-22 | 安徽工业大学 | It is a kind of based on eutectic solvent be solvent embedding system |
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110575439A (en) * | 2019-08-15 | 2019-12-17 | 浙江工业大学 | Construction method of macromolecule/eutectic emulsion and application of macromolecule/eutectic emulsion in solubilization of flavonoid drugs |
| CN110639020A (en) * | 2019-08-15 | 2020-01-03 | 浙江工业大学 | Solid dispersion matrix and preparation method and application thereof |
| CN110639020B (en) * | 2019-08-15 | 2022-07-08 | 浙江工业大学 | Solid dispersion matrix and preparation method and application thereof |
| CN111034718A (en) * | 2019-12-20 | 2020-04-21 | 中国农业大学 | Liquid pesticide preparation and preparation method thereof |
| CN113768871A (en) * | 2021-09-23 | 2021-12-10 | 陕西中医药大学 | Traditional Chinese medicine preparation of hydroxyl carthamin yellow A |
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