CN104706584A - Ivermectin fat emulsion concentrated solution, preparation method and application thereof - Google Patents
Ivermectin fat emulsion concentrated solution, preparation method and application thereof Download PDFInfo
- Publication number
- CN104706584A CN104706584A CN201310686177.7A CN201310686177A CN104706584A CN 104706584 A CN104706584 A CN 104706584A CN 201310686177 A CN201310686177 A CN 201310686177A CN 104706584 A CN104706584 A CN 104706584A
- Authority
- CN
- China
- Prior art keywords
- ivermectin
- fat milk
- concentrated solution
- grams
- content
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
Abstract
An ivermectin fat emulsion concentrated solution, a preparation method and an application thereof belong to the field of pharmacology and pharmaceutics. According to the invention, the defect that a traditional fat emulsion preparation technology is complex and stability is poor is overcome. The preparation technology provided by the invention is simple; the general physical stirring process is only needed; and no homogenization technology is required. A product prepared in the invention can be sterilized through a 0.22-micron microfiltration membrane; and in clinical use, the product can be spontaneously emulsified into a fat emulsion system after diluted by the use of an aqueous solution such as normal saline, etc. and slightly oscillated. The product has good fluidity, will not be retained on the wall, is single-phase, transparent and clear in appearance, can undergo clarification detection, will not cause preparation stratification after multigelation and is applied in controlling gastrointestinal nematodiasis, hypodermosis, Hypoberma Iineata maggot, oestriasis, Psoroptes ovis and swine sarcoptic acariasis of livestock and other parasitic insect diseases.
Description
Technical field
The invention belongs to materia medica and pharmaceutical art, relate to a kind of ivermectin fat milk concentrated solution, Preparation Method And The Use.
Background technology
Ivermectin (Ivermectin, IVM) is first Avermectins medicine derivant that Merck company of the U.S. develops, and with avilamycin ratio, IVM toxicity is less, more stable.Abroad, IVM oneself be widely used in diversified economy animal and the house pets such as dog, cat such as pig, cattle, sheep, rabbit, horse, camel, deer, fox.1996, in global veterinary drug raw material and formulations sold volume, the sales volume of IVM crude drug and primary formulation one Ivomec thereof was first place, reached 7.5 hundred million dollars and 7.35 hundred million dollars respectively.In addition, IVM is also used to filaricide and the people's acariasis of preventing and treating people.1996, the whole world used the people of IVM to reach more than 60 ten thousand.At home, as veterinary drug, oneself starts to widely use IVM in domestic animal and house pet.
Ivermectin poorly water-soluble (4 μ g/ml), for strengthening ivermectin dissolubility, ivermectin nano-composition disclosed in patent CN101623256A, employs a large amount of Tween-80(except aqueous phase, Tween-80 content is up to 65.96%), bring great risk to animal safety.Fat milk (also known as lipid microsphere) is that current field of medicaments develops dosage form faster, can protect coated medicine, can improve medicine stability, prolong drug action time, reduce side effect etc., have certain slow-releasing and targeting.
Fat milk all belongs to Unstable Systems on thermodynamics and kinetics, preparation process has strict requirement to equipment, technological parameter, ratio of adjuvant etc., ivermectin submicron emulsion preparation disclosed in patent CN101590016A, CN101773470A, be exactly typical fat milk, preparation process needs the technique such as colostrum, high pressure homogenize.In addition, existing fat milk needs Special Equipment under high pressure sterilizing.Known by the art personnel, fat milk product need be preserved under 2 ~ 8 DEG C of conditions, and will strictly avoid freezing, and China culture zone is distributed in the north more, and this gives the transport in winter, storage is made troubles.
A desirable ivermectin fat milk is the characteristic that can keep lipid microsphere, has that preparation stability is high, appearance transparent is limpid, technique is simple, without the need to special installation simultaneously, can be degerming by microporous filter membrane mode, to reduce production cost.
Summary of the invention
The present inventor is through deep research and performing creative labour, obtain a kind of ivermectin fat milk concentrated solution, the present inventor is surprised to find, and ivermectin fat milk concentrated solution of the present invention, after mixing with water, without homogenizing means, stable emulsion can be formed, can effectively overcome Oil-water separation phenomenon, and the preparation lamination that can effectively overcome the density contrast between different auxiliary material and bring, obtain single-phase, transparent, stable thus, meeting after water can the fat milk of spontaneous emulsification
Concentrated solution, particularly a kind of ivermectin fat milk concentrated solution.Thus provide following invention:
One aspect of the present invention relates to a kind of ivermectin fat milk concentrated solution, and it comprises:
Principal agent: ivermectin,
Oil: medium chain length fatty acid triglyceride,
Cosolvent: 1,2-PD,
Low hlb surfactant (4≤HLB≤9): phospholipid, and
High hlb surfactant (HLB >=12): polyethyleneglycol-12-hydroxy stearin and/or polyoxyethylene ether (35) Oleum Ricini;
Alternatively, described oil also comprises soybean oil;
Alternatively, described low hlb surfactant also comprises polyglycerol acrylate;
Alternatively, described high hlb surfactant also comprises Tween 80.
Ivermectin fat milk concentrated solution according to any one of the present invention, is characterized in that any one in the item of following (1)-(5) or multinomial:
(1) content of described ivermectin is 1-20%(w/w), be preferably 5-15%(w/w);
(2) content of described oil is 45-85%(w/w), be preferably 50-70%(w/w);
(3) content of described cosolvent is 5-30%(w/w), be preferably 5-20%(w/w);
(4) content of described low hlb surfactant is 5%-20%(w/w);
(5) content of described high hlb surfactant is 5%-20%(w/w).
Ivermectin fat milk concentrated solution according to any one of the present invention, is characterized in that any one in the item of following (1)-(9) or multinomial:
(1) content of described ivermectin is 5-15%(w/w), be preferably 7.5-12%(w/w);
(2) content of described medium chain length fatty acid triglyceride is 20%-70%(w/w), be preferably 25%-65%(w/w);
(3) content of described soybean oil is 0-50%(w/w), be preferably 0-30%(w/w);
(4) content of described 1,2-PD is 5%-15%(w/w), be preferably 7.5%-10%(w/w);
(5) content of described phospholipid is 5%-15%(w/w), be preferably 6.5%-10.5%(w/w);
(6) content of described polyglycerol acrylate is 0-8%(w/w), be preferably 0-5%(w/w);
(7) content of described polyethyleneglycol-12-hydroxy stearin is 0-15%(w/w), be preferably 0-10%(w/w);
(8) content of described Tween 80 is 0-15%(w/w), be preferably 0-10%(w/w);
(9) content of described polyoxyethylene ether (35) Oleum Ricini is 0-15%(w/w), be preferably 0-10%(w/w).
Ivermectin fat milk concentrated solution according to any one of the present invention, is characterized in that any one in the item of following (1)-(5) or multinomial:
(1) the not moisture or water content of the ivermectin fat milk concentrated solution described in is lower than 1%;
(2) the ivermectin fat milk concentrated solution described in is not containing saccharide;
(3) the unambiguous essence of ivermectin fat milk concentrated solution described in;
(4) the ivermectin fat milk concentrated solution its preparation method described in does not comprise removing or falls low-moisture step (such as rotary evaporation, spraying dry or lyophilization);
(5) alternatively, described ivermectin fat milk concentrated solution also comprises antioxidant; Particularly, described antioxidant be selected from oleic acid, enuatrol, vitamin E and vitamin A any one or multiple;
(6) the ivermectin fat milk concentrated solution described in is transparent, single phase soln.
Ivermectin fat milk concentrated solution according to any one of the present invention, its component and content are as below 1)-2) shown in group any one group:
1）
Ivermectin 7.5 ~ 12 grams
Medium chain length fatty acid triglyceride 25 ~ 65 grams
Soybean oil 0 ~ 30 gram
1,2-PD 7.5 ~ 10 grams
Soybean lecithin 6.5 ~ 10.5 grams
Polyglycerol acrylate 0 ~ 5 gram
Polyethyleneglycol-12-hydroxy stearin 5 ~ 10 grams
Tween 80 2 ~ 10 grams
Oleic acid 0 ~ 0.3 gram
Enuatrol 0 ~ 0.3 gram
Vitamin E 0 ~ 0.3 gram;
2）
Ivermectin 7.5 ~ 12 grams
Medium chain length fatty acid triglyceride 55 ~ 65 grams
1,2-PD 9 ~ 10 grams
Soybean lecithin 6.5 ~ 10.5 grams
Polyglycerol acrylate 0 ~ 5 gram
Polyoxyethylene ether (35) Oleum Ricini 8 ~ 10 grams
Oleic acid 0 ~ 0.3 gram
Enuatrol 0 ~ 0.3 gram
Vitamin E 0 ~ 0.3 gram.
Ivermectin fat milk concentrated solution according to any one of the present invention, its component and content are as shown in any a group in (1) below-(4) group:
（1）
Ivermectin 7.6 grams
Medium chain length fatty acid triglyceride (Capmul MCM, Abitec) 26.6 grams
Soybean oil 26.6 grams
1,2-PD 8.3 grams
Soybean lecithin 9.4 grams
Polyglycerol acrylate 3.1 grams
Polyethyleneglycol-12-hydroxy stearin (Solutol HS 15, BASF) 10 grams
Tween 80 8.2 grams
Oleic acid 0.1 gram
Vitamin E 0.1 gram;
（2）
Ivermectin 10.8 grams
Medium chain length fatty acid triglyceride (Capmul MCM, Abitec) 60 grams
1,2-PD 7.5 grams
Soybean lecithin 6.7 grams
Polyglycerol acrylate 3.7 grams
Polyethyleneglycol-12-hydroxy stearin (Solutol HS 15, BASF) 7.4 grams
Tween 80 3.7 grams
Oleic acid 0.1 gram
Vitamin E 0.1 gram;
（3）
Ivermectin 11.7 grams
Medium chain length fatty acid triglyceride (Capmul MCM, Abitec) 59.7 grams
1,2-PD 9.4 grams
Soybean lecithin 10.5 grams
Polyoxyethylene ether (35) Oleum Ricini (Cremophor EL, BASF) 8.7 grams;
（4）
Ivermectin 10.9 grams
Medium chain length fatty acid triglyceride (Crodamol, GTCC) 60.6 grams
1,2-PD 9 grams
Soybean lecithin 6.7 grams
Polyglycerol acrylate 4.5 grams
Polyoxyethylene ether (35) Oleum Ricini (Cremophor EL, BASF) 8.2 grams
Enuatrol 0.1 gram.
It should be noted that, above-mentioned 1)-2) unit of gram in group or (1)-(4) group represents and if be revised as other unit of weight, includes but not limited to ratio between each component, such as kilogram etc., also all within protection scope of the present invention.
Another aspect of the invention relates to a kind of ivermectin fat milk, and its ivermectin fat milk concentrated solution according to any one of the present invention injects and obtains with water self emulsifying; Particularly, described ivermectin fat milk mean diameter is 0.01-0.7 μm; Be preferably 0.1-0.4 μm; More preferably, be 0.11-0.24 μm.
Ivermectin fat milk concentrated solution of the present invention can spontaneous emulsification be ivermectin fat milk after meeting water dilution.
Another aspect of the invention relates to the preparation method of the ivermectin fat milk concentrated solution according to any one of the present invention, comprises the steps:
1) at 20-45 DEG C, low hlb surfactant is added oil, under 1000-10000rpm condition, be stirred to and form transparent clear solution;
2) under 20-45 DEG C of condition, ivermectin, cosolvent, high hlb surfactant and optional antioxidant are added step 1) product, and under 200-2000rpm stirring condition Keep agitation, until the transparent limpid shape of whole system, after 0.22 μm of microporous filter membrane is degerming, final acquisition ivermectin fat milk concentrated solution.
About step 1) or step 2) in the oil, low hlb surfactant, high hlb surfactant and the cosolvent that use, wherein moisture will lower than 1%, or do not have free water.
Step 2) in product, without removing or low-moisture step (such as rotary evaporation, spraying dry or lyophilization) is fallen, water content is lower than 1%(by weight percentage).
Another aspect of the invention relates to ivermectin fat milk concentrated solution according to any one of the present invention or ivermectin fat emulsion formulation of the present invention and is preventing and treating the sick and pig's sarcoptidosis of the Biocontrol of Gastrointestinal Nematodes of poultry, warble, grain leather fly larvae, sheep nose fly larvae, psoroptes communis, and the application in other parasitic insect diseases.
The explanation of the part term that the present invention relates to:
In the present invention, for the percentage ratio of the content of each component, if not otherwise specified, the percentage by weight (w/w) accounting for pharmaceutical composition gross weight is all referred to.
The beneficial effect of the invention
Good product mobility of the present invention, not wall built-up, outward appearance is single-phase, transparent, limpid shape, after multigelation, preparation lamination can not occur; Product of the present invention is met water and is formed in ivermectin fat milk plant process, only needs slight oscillatory can spontaneous emulsification, through aqueous solution dilutions such as normal saline and after slight oscillatory, can spontaneous emulsification be fat milk system during use.
Product of the present invention, adjuvant used is pharmaceutical grade, and safety is high, environmental friendliness.Preparation technology of the present invention is simple, only relates to normal agitation process, is easy to transport, stores, have application prospect.
Detailed description of the invention
Below in conjunction with embodiment, embodiment of the present invention are described in detail, but it will be understood to those of skill in the art that the following example only for illustration of the present invention, and should not be considered as limiting scope of the present invention.Unreceipted actual conditions person in embodiment, the condition of conveniently conditioned disjunction manufacturer suggestion is carried out.Agents useful for same or the unreceipted production firm person of instrument, being can by the conventional products of commercial acquisition.
Embodiment 1: the preparation of ivermectin fat milk concentrated solution sample 1
Its constituent is as follows:
Ivermectin 7.6 grams
Medium chain length fatty acid triglyceride (Capmul MCM, Abitec) 26.6 grams
Soybean oil 26.6 grams
1,2-PD 8.3 grams
Soybean lecithin 9.4 grams
Polyglycerol acrylate 3.1 grams
Polyethyleneglycol-12-hydroxy stearin (Solutol HS 15, BASF) 10 grams
Tween 80 8.2 grams
Oleic acid 0.1 gram
Vitamin E 0.1 gram
This ivermectin fat milk concentrated solution preparation method is as follows:
1) at 20 DEG C, the soybean lecithin of above-mentioned weight, polyglycerol acrylate are added in medium chain length fatty acid triglyceride and soybean oil, under 8000rpm condition, be stirred to and form transparent clear solution;
2) under 45 DEG C of conditions, by the ivermectin of above-mentioned weight, 1,2-propylene glycol, polyethyleneglycol-12-hydroxy stearin, Tween 80, oleic acid, vitamin E add step 1) product, and under 1000rpm stirring condition Keep agitation, until the transparent limpid shape of whole system, after 0.22 μm of microporous filter membrane is degerming, final acquisition ivermectin fat milk concentrated solution.
Embodiment 2: the preparation of ivermectin fat milk concentrated solution sample 2
Its constituent is as follows:
Ivermectin 10.8 grams
Medium chain length fatty acid triglyceride (Capmul MCM, Abitec) 60 grams
1,2-PD 7.5 grams
Soybean lecithin 6.7 grams
Polyglycerol acrylate 3.7 grams
Polyethyleneglycol-12-hydroxy stearin (Solutol HS 15, BASF) 7.4 grams
Tween 80 3.7 grams
Oleic acid 0.1 gram
Vitamin E 0.1 gram
This ivermectin fat milk concentrated solution preparation method is as follows:
1) at 45 DEG C, the soybean lecithin of above-mentioned weight, polyglycerol acrylate are added medium chain length fatty acid triglyceride, under 10000rpm condition, be stirred to and form transparent clear solution;
2) under 20 DEG C of conditions, by the ivermectin of above-mentioned weight, 1,2-propylene glycol, polyethyleneglycol-12-hydroxy stearin, Tween 80, oleic acid, vitamin E add step 1) product, and under 2000rpm stirring condition Keep agitation, until the transparent limpid shape of whole system, after 0.22 μm of microporous filter membrane is degerming, final acquisition ivermectin fat milk concentrated solution.
Embodiment 3: the preparation of ivermectin fat milk concentrated solution sample 3
Its constituent is as follows:
Ivermectin 11.7 grams
Medium chain length fatty acid triglyceride (Capmul MCM, Abitec) 59.7 grams
1,2-PD 9.4 grams
Soybean lecithin 10.5 grams
Polyoxyethylene ether (35) Oleum Ricini (Cremophor EL, BASF) 8.7 grams
This ivermectin fat milk concentrated solution preparation method is as follows:
1) at 25 DEG C, the soybean lecithin of above-mentioned weight is added medium chain length fatty acid triglyceride, under 1000rpm condition, be stirred to and form transparent clear solution;
2) under 25 DEG C of conditions, by the ivermectin of above-mentioned weight, 1,2-propylene glycol, polyoxyethylene ether (35) Oleum Ricini add step 1) product, and under 200rpm stirring condition Keep agitation, until the transparent limpid shape of whole system, after 0.22 μm of microporous filter membrane is degerming, final acquisition ivermectin fat milk concentrated solution.
Embodiment 4: the preparation of ivermectin fat milk concentrated solution sample 4
Its constituent is as follows:
Ivermectin 10.9 grams
Medium chain length fatty acid triglyceride (Crodamol, GTCC) 60.6 grams
1,2-PD 9 grams
Soybean lecithin 6.7 grams
Polyglycerol acrylate 4.5 grams
Polyoxyethylene ether (35) Oleum Ricini (Cremophor EL, BASF) 8.2 grams
Enuatrol 0.1 gram
This ivermectin fat milk concentrated solution preparation method is as follows:
1) at 25 DEG C, the soybean lecithin of above-mentioned weight, polyglycerol acrylate are added medium chain length fatty acid triglyceride, under 3000rpm condition, be stirred to and form transparent clear solution;
2) under 25 DEG C of conditions, by the ivermectin of above-mentioned weight, 1,2-propylene glycol, polyoxyethylene ether (35) Oleum Ricini, enuatrol add step 1) product, and under 200rpm stirring condition Keep agitation, until the transparent limpid shape of whole system, after 0.22 μm of microporous filter membrane is degerming, final acquisition ivermectin fat milk concentrated solution.
embodiment 5: stability test
Sample 1-4 prepared by embodiment 1-4.
Experimental technique: by different sample after-20 DEG C of freeze overnight, is positioned over 20 DEG C and naturally thaws, and multigelation like this 6 times, observes sample appearance under environmental condition, and measures change of size before and after freeze thawing.
Droplet measurement method: adopt Malvern Zetasizer 3000HSA Particle Size Analyzer to detect particle diameter, before mensuration, sample adds the normal saline of 10 times of volumes, measures after slight oscillatory spontaneous emulsification.
Table 1: different sample is after freeze thawing, and sample appearance changes
| Sample | Cosmetic variation |
| 1 | Outward appearance is clarified, not stratified, not wall built-up, good fluidity |
| 2 | Outward appearance is clarified, not stratified, not wall built-up, good fluidity |
| 3 | Outward appearance is clarified, not stratified, not wall built-up, good fluidity |
| 4 | Outward appearance is clarified, not stratified, not wall built-up, good fluidity |
Table 2: different sample average particle diameter
From table 1, sample 1-4 all has fabulous stability, and through multigelation, outward appearance still can keep transparent homogeneous phase, not wall built-up, not stratified, has good mobility.As shown in Table 2, the mean diameter after the emulsifying of four embodiment products, between 110 ~ 250nm, belong to typical fat milk product, and particle diameter does not affect by concentrated emulsion freeze thawing.
Although the specific embodiment of the present invention has obtained detailed description, it will be understood to those of skill in the art that.According to disclosed all instructions, can carry out various amendment and replacement to those details, these change all within protection scope of the present invention.Four corner of the present invention is provided by claims and any equivalent thereof.
Claims (8)
1. an ivermectin fat milk concentrated solution, it comprises:
Principal agent: ivermectin,
Oil: medium chain length fatty acid triglyceride,
Cosolvent: 1,2-PD,
Low hlb surfactant: phospholipid, and
High hlb surfactant: polyethyleneglycol-12-hydroxy stearin and/or polyoxyethylene ether (35) Oleum Ricini;
Alternatively, described oil also comprises soybean oil;
Alternatively, described low hlb surfactant also comprises polyglycerol acrylate;
Alternatively, described high hlb surfactant also comprises Tween 80.
2. ivermectin fat milk concentrated solution according to claim 1, is characterized in that any one in the item of following (1)-(5) or multinomial:
(1) content of described ivermectin is 1-20%(w/w); Be preferably 5-15%(w/w);
(2) content of described oil is 45-85%(w/w); Be preferably 50-70%(w/w);
(3) content of described cosolvent is 5-30%(w/w); Be preferably 5-20%(w/w);
(4) content of described low hlb surfactant is 5%-20%(w/w);
(5) content of described high hlb surfactant is 5%-20%(w/w).
3., according to the ivermectin fat milk concentrated solution described in claim 1 to 2, it is characterized in that any one in the item of following (1)-(9) or multinomial:
(1) content of described ivermectin is 5-15%(w/w), be preferably 7.5-12%(w/w);
(2) content of described medium chain length fatty acid triglyceride is 20%-70%(w/w), be preferably 25%-65%(w/w);
(3) content of described soybean oil is 0-50%(w/w), be preferably 0-30%(w/w);
(4) content of described 1,2-PD is 5%-15%(w/w), be preferably 7.5%-10%(w/w);
(5) content of described phospholipid is 5%-15%(w/w), be preferably 6.5%-10.5%(w/w);
(6) content of described polyglycerol acrylate is 0-8%(w/w), be preferably 0-5%(w/w);
(7) content of described polyethyleneglycol-12-hydroxy stearin is 0-15%(w/w), be preferably 0-10%(w/w);
(8) content of described Tween 80 is 0-15%(w/w), be preferably 0-10%(w/w);
(9) content of described polyoxyethylene ether (35) Oleum Ricini is 0-15%(w/w), be preferably 0-10%(w/w).
4. ivermectin fat milk concentrated solution according to any one of claim 1 to 3, is characterized in that following
(1) any one-(6) in item or multinomial:
(1) the not moisture or water content of the ivermectin fat milk concentrated solution described in is lower than 1%;
(2) the ivermectin fat milk concentrated solution described in is not containing saccharide;
(3) the unambiguous essence of ivermectin fat milk concentrated solution described in;
(4) the ivermectin fat milk concentrated solution its preparation method described in does not comprise removing or falls low-moisture step (such as rotary evaporation, spraying dry or lyophilization);
(5) alternatively, described ivermectin fat milk concentrated solution also comprises antioxidant; Particularly, described antioxidant be selected from oleic acid, enuatrol, vitamin E and vitamin A any one or multiple;
(6) the ivermectin fat milk concentrated solution described in is transparent, single phase soln.
5. an ivermectin fat milk concentrated solution, its component and content are as 1 below)-2) shown in group any one group:
1）
Ivermectin 7.5 ~ 12 grams
Medium chain length fatty acid triglyceride 25 ~ 65 grams
Soybean oil 0 ~ 30 gram
1,2-PD 7.5 ~ 10 grams
Soybean lecithin 6.5 ~ 10.5 grams
Polyglycerol acrylate 0 ~ 5 gram
Polyethyleneglycol-12-hydroxy stearin 5 ~ 10 grams
Tween 80 2 ~ 10 grams
Oleic acid 0 ~ 0.3 gram
Enuatrol 0 ~ 0.3 gram
Vitamin E 0 ~ 0.3 gram;
2）
Ivermectin 7.5 ~ 12 grams
Medium chain length fatty acid triglyceride 55 ~ 65 grams
1,2-PD 9 ~ 10 grams
Soybean lecithin 6.5 ~ 10.5 grams
Polyglycerol acrylate 0 ~ 5 gram
Polyoxyethylene ether (35) Oleum Ricini 8 ~ 10 grams
Oleic acid 0 ~ 0.3 gram
Enuatrol 0 ~ 0.3 gram
Vitamin E 0 ~ 0.3 gram.
6. an ivermectin fat milk, its ivermectin fat milk concentrated solution according to any one of claim 1 to 5 injects and obtains with water self emulsifying; Particularly, described ivermectin fat milk mean diameter is 0.01-0.7 μm; Be preferably 0.1-0.4 μm; More preferably, be 0.11-0.24 μm.
7. the preparation method of the ivermectin fat milk concentrated solution according to any one of claim 1 to 5, comprises the steps:
1) at 20-45 DEG C, low hlb surfactant is added oil, under 1000-10000rpm condition, be stirred to and form transparent clear solution;
2) under 20-45 DEG C of condition, ivermectin, cosolvent, high hlb surfactant and optional antioxidant are added step 1) product, and under 200-2000rpm stirring condition Keep agitation, until the transparent limpid shape of whole system, after 0.22 μm of microporous filter membrane is degerming, final acquisition ivermectin fat milk concentrated solution.
8. the ivermectin fat milk concentrated solution according to any one of claim 1 to 5 or ivermectin fat emulsion formulation according to claim 6 are preventing and treating the sick and pig's sarcoptidosis of the Biocontrol of Gastrointestinal Nematodes of poultry, warble, grain leather fly larvae, sheep nose fly larvae, psoroptes communis, and the application in other parasitic insect diseases.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201310686177.7A CN104706584A (en) | 2013-12-16 | 2013-12-16 | Ivermectin fat emulsion concentrated solution, preparation method and application thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201310686177.7A CN104706584A (en) | 2013-12-16 | 2013-12-16 | Ivermectin fat emulsion concentrated solution, preparation method and application thereof |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN104706584A true CN104706584A (en) | 2015-06-17 |
Family
ID=53406634
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201310686177.7A Pending CN104706584A (en) | 2013-12-16 | 2013-12-16 | Ivermectin fat emulsion concentrated solution, preparation method and application thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN104706584A (en) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN108992403A (en) * | 2018-08-31 | 2018-12-14 | 田红卫 | A kind of long-acting slow-release ivermectin injection and preparation method thereof |
| WO2022069922A1 (en) * | 2020-09-30 | 2022-04-07 | Procaps S.A. | Formulation of ivermectin in soft gelatin capsules |
Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1241404A (en) * | 1999-07-16 | 2000-01-19 | 王玉万 | Avermectin-or ivermectin-containing slow releasing injecta |
| WO2004093886A1 (en) * | 2003-04-24 | 2004-11-04 | Galderma S.A. | Topical formulation of ivermectin for the treatment of dermatological conditions |
| CN101623256A (en) * | 2008-07-08 | 2010-01-13 | 中国农业科学院兰州畜牧与兽药研究所 | Ivermectin nanoemulsion drug combination and preparation method thereof |
| CN101926757A (en) * | 2010-09-01 | 2010-12-29 | 北京大学 | Liquid composition of indissolvable medicines and preparation method thereof |
| CN103417478A (en) * | 2012-05-18 | 2013-12-04 | 中国农业科学院兰州畜牧与兽药研究所 | Water based ivermectin O/W injection and preparation method thereof |
-
2013
- 2013-12-16 CN CN201310686177.7A patent/CN104706584A/en active Pending
Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1241404A (en) * | 1999-07-16 | 2000-01-19 | 王玉万 | Avermectin-or ivermectin-containing slow releasing injecta |
| WO2004093886A1 (en) * | 2003-04-24 | 2004-11-04 | Galderma S.A. | Topical formulation of ivermectin for the treatment of dermatological conditions |
| CN101623256A (en) * | 2008-07-08 | 2010-01-13 | 中国农业科学院兰州畜牧与兽药研究所 | Ivermectin nanoemulsion drug combination and preparation method thereof |
| CN101926757A (en) * | 2010-09-01 | 2010-12-29 | 北京大学 | Liquid composition of indissolvable medicines and preparation method thereof |
| CN103417478A (en) * | 2012-05-18 | 2013-12-04 | 中国农业科学院兰州畜牧与兽药研究所 | Water based ivermectin O/W injection and preparation method thereof |
Non-Patent Citations (1)
| Title |
|---|
| 赵永星等: ""注射用伊维菌素亚微乳的制备及其稳定性研究"", 《中国兽药杂志》 * |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN108992403A (en) * | 2018-08-31 | 2018-12-14 | 田红卫 | A kind of long-acting slow-release ivermectin injection and preparation method thereof |
| WO2022069922A1 (en) * | 2020-09-30 | 2022-04-07 | Procaps S.A. | Formulation of ivermectin in soft gelatin capsules |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| HRP20090573T1 (en) | Method for solubilizing, dispersing, and stabilizing materials, products manufactured according to said method, and use thereof | |
| AU2008260443A1 (en) | Stable biocidal composition | |
| CN101822638A (en) | Nano-emulsion of stilbene compound and preparation method thereof | |
| CN107410295A (en) | The Fluoxastrobin aqueous suspension agent of a kind of particle diameter less than 100 nanometers and preparation method thereof | |
| CN104706592A (en) | Oral ivermectin microemulsion concentrate and preparation method and application thereof | |
| CN104706584A (en) | Ivermectin fat emulsion concentrated solution, preparation method and application thereof | |
| Bjerregaard et al. | Sustained elevated plasma aprotinin concentration in mice following intraperitoneal injections of w/o emulsions incorporating aprotinin | |
| CN102657610A (en) | 3,5-dihydroxyl4-isopropyl diphenylethylene micro-emulsion and preparation method thereof | |
| CN101336901B (en) | Anti-coccidium microemulsion containing toltrazuril and preparation method thereof | |
| CN104069266B (en) | A kind of plant essential oil composition for animals | |
| CN102058545B (en) | Meropenem freeze-dried preparation for injection and preparation method thereof | |
| JP2020503244A (en) | Self-emulsifying lipid composition | |
| CN104083324B (en) | Veterinary suspoemulsion containing rifaximin as well as preparation method and application thereof | |
| CN101982176A (en) | Compound sodium selenite-vitamin E oral nano-emulsion preparation for livestock and preparation method thereof | |
| KR20200003156A (en) | Stabilized compositions for controlled delivery of probiotics and methods of making the same | |
| US20220024830A1 (en) | Liquid products having increased solids concentrations | |
| CN104706574A (en) | Dexamethasone palmitate fat emulsion concentrated solution, preparation method and application thereof | |
| US11007202B2 (en) | Pheromone compositions for stimulating early onset of estrus and reducing labor needs in breeding peri-pubertal suids and methods of use | |
| CN104706585A (en) | Vinorelbine bitartrate fat emulsion concentrated solution, preparation method and application thereof | |
| CN104705316A (en) | Abamectin microemulsion concentrate and preparation method and application thereof | |
| US20230201285A1 (en) | Granular composition providing water dispersible cannabinoids and methods of making the same | |
| CN101185442A (en) | Compound pesticides water emulsion agent containing fipronil and triazophos and preparation method thereof | |
| CN104706588A (en) | Vinpocetine fat emulsion concentrated solution, preparation method and application thereof | |
| CN107027749A (en) | A kind of compound emulsifying agent and its application in compounding chlopyrifos pesticides | |
| CN103108624A (en) | Non-aqueous oily injectable formulation exhibiting preservative efficacy |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| WD01 | Invention patent application deemed withdrawn after publication | ||
| WD01 | Invention patent application deemed withdrawn after publication |
Application publication date: 20150617 |