CN109223710A - Molecule micro emulsion and preparation method thereof for preventing and treating chicken leucocyte protozoon - Google Patents
Molecule micro emulsion and preparation method thereof for preventing and treating chicken leucocyte protozoon Download PDFInfo
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- CN109223710A CN109223710A CN201811051298.3A CN201811051298A CN109223710A CN 109223710 A CN109223710 A CN 109223710A CN 201811051298 A CN201811051298 A CN 201811051298A CN 109223710 A CN109223710 A CN 109223710A
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- pyrimethamine
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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
- A61K9/10—Dispersions; Emulsions
- A61K9/107—Emulsions ; Emulsion preconcentrates; Micelles
- A61K9/1075—Microemulsions or submicron emulsions; Preconcentrates or solids thereof; Micelles, e.g. made of phospholipids or block copolymers
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/715—Polysaccharides, i.e. having more than five saccharide radicals attached to each other by glycosidic linkages; Derivatives thereof, e.g. ethers, esters
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/26—Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P33/00—Antiparasitic agents
- A61P33/02—Antiprotozoals, e.g. for leishmaniasis, trichomoniasis, toxoplasmosis
Abstract
The invention discloses a kind of for preventing and treating the molecule micro emulsion of chicken leucocyte protozoon, the component including following parts by weight: 0.1~1.5 part of pyrimethamine, 1~10 part of astragalus polyose, 3~20 parts of emulsifier, 0.01~0.8 part of antioxidant, 1~20 part of solvent and 0.05~1 part of preservative.Cooperation specifically has enhancing immunity of organisms to be used together with the astragalus polyose for improving body items production performance while preventing and treating Chicken Leucocyte Pest using pyrimethamine, can effectively high-drug-effect and reduce pyrimethamine side effect, make treatment after body quickly lapse to recovery.
Description
Technical field
The present invention relates to animal pharmaceuticals fields, and in particular to a kind of for preventing and treating the molecule micro emulsion of chicken leucocyte protozoon
And preparation method thereof.
Background technique
Chicken leucocyte protozoon be by live Leucocytozoon it is a variety of live coccidium syphilidis parasitize the leucocyte of chicken and red
A kind of acute blood spore protozoosis caused by cell.For diseased chicken because red blood cell is destroyed and extensive bleeding, cockscomb is in pale asphyxia, therefore
Also known as white comb.This disease is in many regional outbreak of epidemic in China in recent years, is on the rise disease to the harm of poultry husbandry.Original is lived white thin
Born of the same parents' Eimeria pushes up subphylum in protozoa again, sporozoa, Haemosporea, Plasmodiidae, firmly Leucocytozoon.China
It has been found that chicken has 2 kinds to live coccidium syphilidis: Leucocytozoon caulleryi and Sharpe live coccidium syphilidis.
In clinical symptoms, the chick of infection and Growing Chicken are obvious.Diseased chicken body temperature rises, lassitude, head piece
Water, drain shape green excrement, serious anaemia, wattle and cockscomb whiten, and the different paralysis of degree occur, mouth breathing is exhaled
Difficult, cough is inhaled, sometimes band blood.Chick and the Growing Chicken death rate are higher.Adult Chicken does not cause death generally, clinically only
Show as thin and weak, cockscomb and wattle whiten, anaemia, row's green or white watery stools, hypoevolutism, laying rate and egg production
It is decreased obviously.
Pyrimethamine is a kind of antiprotozoal drug for being widely used in the mankind, has preferable effect to the treatment of plasmodium, is come
It prevents and treats Chicken Leucocyte Pest to work well, this is to prevent and treat chicken for substituting sulfamido and nitrofurans and live
Leucocyte parasitosis drug best at present.But the side effect of pyrimethamine is larger, safe range is smaller, and being excessively used can damage
The reproductive system of livestock and poultry, and be not easy to restore, it is noted that dosage and time when by it applied to livestock and poultry.
It is good that pyrimethamine by per kilogram of body weight prevents and treats Chicken Leucocyte Pest effect with 1 milligram of pyrimethamine
Good, common pyrimethamine pre-mixing agent and granule often occur causing mixing uneven since pyrimethamine additive amount is very few
The case where.If cleaning, which is not thorough, will lead to pyrimethamine medicament residue in production and use process, how to guarantee pyrimethamine
It is always pyrimethamine production and the critical issue that uses using safe and prevent the residue problem of use process drug.
It would therefore be highly desirable to develop a kind of guarantee pyrimethamine use it is safe and prevent the remaining use of drug in use process
In the molecule micro emulsion of prevention and treatment chicken leucocyte protozoon.
Summary of the invention
The object of the present invention is to provide a kind of molecule micro emulsion and preparation method thereof for preventing and treating chicken leucocyte protozoon,
The microemulsion can arbitrarily match use with water, and feeding is convenient, reduce consumption loss and medicament residue, ensure food safety.
To achieve the goals above, following technical proposals are taken:
It is a kind of for preventing and treating the molecule micro emulsion of chicken leucocyte protozoon, the component including following parts by weight: ethamine is phonetic
0.1~1.5 part of pyridine, 1~10 part of astragalus polyose, 3~20 parts of emulsifier, 0.01~0.8 part of antioxidant, 0.1~22 part of solvent
With 0.05~1 part of preservative.
Preferably, the molecule micro emulsion for being used to prevent and treat chicken leucocyte protozoon, the group including following parts by weight
Point: 0.5~1 part of pyrimethamine, 3~10 parts of astragalus polyose, 5~20 parts of emulsifier, 0.01~0.3 part of antioxidant, solvent 1~
15 parts and 0.05~0.5 part of preservative.
Preferably, the emulsifier is selected from Tween 80, polysorbate60, polysorbas20, sorbester p18, sorbester p17, span 85, hydrogenation
One or more of Emulsifier EL-60 and Emulsifier EL-60.
Preferably, the solvent is selected from one or more of glacial acetic acid, ethyl alcohol, water and dimethyl acetamide.
Preferably, the antioxidant is selected from one or more of BHA, BHT and propylgallate.
Preferably, the preservative is selected from one or more of EDTA, benzoic acid, sodium benzoate and potassium sorbate.
It is a kind of for preventing and treating the preparation method of the molecule micro emulsion of chicken leucocyte protozoon, comprising the following steps:
(1) each component is weighed in parts by weight；
(2) pyrimethamine is dissolved using solvent, obtains pyrimethamine solution；
(3) antioxidant and preservative are dissolved using solvent respectively, obtain antioxidant solution and antiseptic solution；
(4) the pyrimethamine solution in step (2) and astragalus polyose stirring after emulsifier heating and melting, will be added, obtains
Emulsion；
(5) antioxidant solution obtained by emulsion obtained by step (4) and step (3) and antiseptic solution are mixed,
Filtering with microporous membrane is to get the molecule micro emulsion for preventing and treating chicken leucocyte protozoon.
Preferably, in step (2), the weight ratio of pyrimethamine and solvent is 1:1-10, in step (3), antioxidant with
The weight ratio of solvent is 1:1-5；The weight ratio of preservative and solvent is 1:1-3.
It is furthermore preferred that the ratio of pyrimethamine and glacial acetic acid is 1:1-10 using glacial acetic acid dissolution pyrimethamine；Using second
The ratio of alcohol dissolution antioxidant, antioxidant and ethyl alcohol is 1:1-5；Preservative, the ratio of preservative and water are dissolved using water
It is 1:1-3.
Preferably, in step (4), the heating and melting temperature is 60~120 DEG C, and pyrimethamine solution is added and Radix Astragali is more
The specific steps of sugar are as follows: in the state of heating, pyrimethamine solution and astragalus polyose stirring is added until all melting；It is added
The time of stirring are as follows: 30-60min.
Preferably, in step (5), 10-30min is dispersed with stirring using high-speed homogenization machine, using 100-300nm miillpore filter
Filtering.
The beneficial effects of the invention are that:
1, the present invention provides a kind of molecule micro emulsion and preparation method thereof for preventing and treating chicken leucocyte protozoon, the micro emulsion
Liquid can arbitrarily match use with water, and feeding is convenient, reduce consumption loss and medicament residue, ensure food safety.
2, it is an object of the present invention to provide a kind of for preventing and treating the molecule micro emulsion and its system of chicken leucocyte protozoon
Preparation Method, using pyrimethamine prevent and treat Chicken Leucocyte Pest while cooperation specifically have enhancing immunity of organisms and
The astragalus polyose for improving body items production performance is used together, and can be effectively improved drug effect and be reduced pyrimethamine side effect, make
Body quickly lapses to recovery after treatment.
3, a kind of molecule micro emulsion and preparation method thereof for preventing and treating chicken leucocyte protozoon provided by the invention, side
Method is simple, and effective component is evenly distributed, and overcomes the uniform different problem of content of ordinary preparation.
4, a kind of molecule micro emulsion and preparation method thereof for preventing and treating chicken leucocyte protozoon provided by the invention, mainly
Stable effective ingredients are good, easily stored and transport.
5. the astragalus polyose that the present invention is added is that content is most in Chinese herbal medicine astragalus, the stronger substance of immunocompetence, it is
One of main active of Radix Astragali, have stimulation Development of Immune Organs, enhancing cellular immunity and humoral immunity, induction of cellular because
The effects of sub, antiviral, oxidation-resisting and caducity, and have the characteristics that small natural sex, toxic side effect, noresidue and pollution-free.
Specific embodiment
The following examples can help those skilled in the art that the present invention is more fully understood, but be not limited only to this.
Embodiment 1
It is a kind of for preventing and treating the molecule micro emulsion of chicken leucocyte protozoon, the component including following parts by weight:
It is a kind of for preventing and treating the preparation method of the molecule micro emulsion of chicken leucocyte protozoon, comprising the following steps:
(1) each component is weighed in parts by weight；
(2) pyrimethamine is dissolved with glacial acetic acid, obtains pyrimethamine solution；
(3) BHA is dissolved with ethyl alcohol and is dissolved with potassium sorbate with water, obtain BHA solution and potassium sorbate solution；
(4) Tween 80 and polysorbas20 are heated to 60 DEG C, the pyrimethamine being added in step (2) in the state of heating is molten
Liquid and astragalus polyose stir 60min, until all substances are all melted, obtain emulsion；
(5) BHA solution obtained by emulsion obtained by step (4) and step (3) and potassium sorbate solution are mixed even with high speed
Pulp grinder is dispersed with stirring 30min, with 100nm filtering with microporous membrane to get the molecule micro emulsion for preventing and treating chicken leucocyte protozoon.
Embodiment 2
It is a kind of for preventing and treating the molecule micro emulsion of chicken leucocyte protozoon, the component including following parts by weight:
It is a kind of for preventing and treating the preparation method of the molecule micro emulsion of chicken leucocyte protozoon, comprising the following steps:
(1) each component is weighed in parts by weight；
(2) pyrimethamine is dissolved with glacial acetic acid, obtains pyrimethamine solution；
(3) Tween 80 and polysorbas20 are heated to 70 DEG C, the pyrimethamine being added in step (1) in the state of heating is molten
Liquid and astragalus polyose stir 60min, until all substances are all melted, obtain emulsion；
(4) BHA is dissolved with ethyl alcohol and is dissolved with potassium sorbate with water, obtain BHA solution and potassium sorbate solution；
(5) BHA solution obtained by emulsion obtained by step (3) and step (4) and potassium sorbate solution are mixed even with high speed
Pulp grinder is dispersed with stirring 40min, with 100nm filtering with microporous membrane to get the molecule micro emulsion for preventing and treating chicken leucocyte protozoon.
Embodiment 3
It is a kind of for preventing and treating the molecule micro emulsion of chicken leucocyte protozoon, the component including following parts by weight:
It is a kind of for preventing and treating the preparation method of the molecule micro emulsion of chicken leucocyte protozoon, comprising the following steps:
(1) each component is weighed in parts by weight；
(2) pyrimethamine is dissolved with glacial acetic acid, obtains pyrimethamine solution；
(3) it after hydrogenation Emulsifier EL-60 being heated to 65 DEG C of thawings, is added in step (1) in the state of heating
Pyrimethamine solution and astragalus polyose stir 60min, until all substances are all melted, obtain emulsion；
(4) BHA is dissolved with ethyl alcohol and is dissolved with potassium sorbate with water, obtain BHA solution and potassium sorbate solution；
(5) BHA solution obtained by emulsion obtained by step (3) and step (4) and potassium sorbate solution are mixed even with high speed
Pulp grinder is dispersed with stirring 40min, with 100nm filtering with microporous membrane to get the molecule micro emulsion for preventing and treating chicken leucocyte protozoon.
Beneficial effects of the present invention are described further below by way of test example.
Comparative example 1
It is a kind of for preventing and treating the medicinal powder of chicken leucocyte protozoon, including following parts by weight component:
0.5 part of pyrimethamine,
99.5 parts of soluble starch.
It is a kind of for preventing and treating the preparation method of the medicinal powder of chicken leucocyte protozoon, comprising the following steps:
(1) each component is weighed according to parts by weight；
(2) pyrimethamine and soluble starch are uniformly mixed by equivalent gradually-increased and live leucocyte to get being used to prevent and treat chicken
The medicinal powder of protozoosis.
A kind of test example 1: molecule micro emulsion uniformity of dosage units detection for preventing and treating chicken leucocyte protozoon
1 test objective: prove it is provided by the present invention it is a kind of containing pyrimethamine for preventing and treating chicken leucocyte protozoon
The molecule micro emulsion uniformity of dosage units of disease reaches prescribed requirement.
2 test specimens: a kind of according to prepared by Examples 1 to 3 to live leucocyte for preventing and treating chicken containing pyrimethamine
The molecule micro emulsion of protozoosis, lot number are respectively 17030901,17030902,17030903.
3 test methods: it is examined according to 166 uniformity of dosage units of " Republic of China Veterinary Pharmacopoeia one " (version in 2015) annex
Method is looked into, is examined a kind of for preventing and treating the pyrimethamine uniformity of dosage units of the molecule micro emulsion of chicken leucocyte protozoon.Totally three batches
Secondary, each batch takes ten samples, carries out in accordance with the law.
4 test results are shown in Table 1
Table 1 is containing a kind of for preventing and treating the molecule micro emulsion uniformity of dosage units result of chicken leucocyte protozoon
Note: conclusion standard: mixture homogeneity≤15.0
Test example 1 the result shows that, it is provided by the present invention a kind of for preventing and treating the molecule micro emulsion of chicken leucocyte protozoon
Uniformity of dosage units meets regulation, uniform properties.
A kind of test example 2: molecule stability of microemulsion investigation (accelerated test) for preventing and treating chicken leucocyte protozoon
Test objective: it proves provided by the present invention a kind of for preventing and treating having for the molecule micro emulsion of chicken leucocyte protozoon
Effect ingredient is valid protected in microcapsules, and stability is good, easily stored and transport.
Trial drug: a kind of molecule for preventing and treating chicken leucocyte protozoon according to prepared by Examples 1 to 3 is micro-
Cream, lot number are respectively 17030901,17030902,17030903.And comparative example 1.
Test method: referring to the accelerated test measurement in one stability of " Republic of China Veterinary Pharmacopoeia " version in 2015
Method is detected.By commercially available back, at 40 DEG C ± 2 DEG C of temperature, 6 months are placed under conditions of relative temperature 70% ± 5%, in real time
Monitor temperature and humidity, 1st month during test, 2 months, 3 months, 6 the end of month it is separately sampled primary, detect a kind of for preventing and treating
The content of pyrimethamine in the molecule micro emulsion and comparative example 1 of chicken leucocyte protozoon.
Test result is shown in Table 2
A kind of molecule micro emulsion stable content for preventing and treating chicken leucocyte protozoon of table 2 investigates result
Note: conclusion standard: content labelled amount >=90%
Test example 2 the result shows that, it is provided by the present invention a kind of for preventing and treating the molecule micro emulsion of chicken leucocyte protozoon
By at 40 DEG C ± 2 DEG C of temperature, accelerated test under the conditions of relative temperature 70% ± 5%, content remains to reach standard regulation
On, effective component is valid protected in micro emulsion, and stability is good, easily stored and transport.And the ethamine of general formulation is phonetic fixed
Pre-mixing agent passes through 6 months accelerated tests, and content has descended to standard value or less.
A kind of test example 3: molecule micro emulsion treatment chicken leucocyte protozoon examination for preventing and treating chicken leucocyte protozoon
It tests
Test objective: it proves provided by the present invention a kind of for preventing and treating pair of the molecule micro emulsion of chicken leucocyte protozoon
The therapeutic effect of chicken leucocyte protozoon.
Trial drug: it is a kind of for preventing and treating the molecule micro emulsion of chicken leucocyte protozoon according to prepared by embodiment 1, batch
Number be 17030901 and comparative example 1 (not adding Huang Shi polysaccharide).Control group: compound Thailand goes out net (the prevention and treatment chicken that can be bought on the market
The drug of leucocyte protozoon disease), it is produced by Shandong company.
Test method: learn from else's experience end slightly blood smear and microscopy are diagnosed as the chicken of 15 ages in days of infection chicken leucocyte protozoon
It only, is not medication group, test group and control group, each test group 120.It is added in test group and the drinking water per ton of comparative example 1
This product 500g, i.e. per kilogram drinking water add 0.5g.Compound Thailand goes out only according to recommendation dosage by 0.1% spice, i.e. per kilogram material
Add 1g.
Test result is shown in Table 3
A kind of molecule micro emulsion treatment chicken for preventing and treating chicken leucocyte protozoon containing pyrimethamine of table 3 lives leucocyte
Protozoosis test result
Test example 3 the result shows that, it is provided by the present invention a kind of for preventing and treating the molecule micro emulsion of chicken leucocyte protozoon
Good to the therapeutic effect of chicken leucocyte protozoon, body quickly lapses to recovery after treatment.Than not adding the micro- of astragalus polyose
Emulsion effect is obviously good, better than sulfonamides (drug of prevention and treatment chicken leucocyte protozoon i.e. on the market) using effect, answers
It is few to swash reaction.
Claims (10)
1. a kind of for preventing and treating the molecule micro emulsion of chicken leucocyte protozoon, which is characterized in that the group including following parts by weight
Point: 0.1~1.5 part of pyrimethamine, 1~10 part of astragalus polyose, 3~20 parts of emulsifier, 0.01~0.8 part of antioxidant, solvent
0.1~22 part and 0.05~1 part of preservative.
2. according to claim 1 for preventing and treating the molecule micro emulsion of chicken leucocyte protozoon, which is characterized in that including with
The component of lower parts by weight: 0.5~1 part of pyrimethamine, 3~10 parts of astragalus polyose, 5~20 parts of emulsifier, antioxidant 0.01
~0.3 part, 1~15 part of solvent and 0.05~0.5 part of preservative.
3. according to claim 1 or 2 for preventing and treating the molecule micro emulsion of chicken leucocyte protozoon, which is characterized in that institute
The emulsifier stated be selected from Tween 80, polysorbate60, polysorbas20, sorbester p18, sorbester p17, span 85, hydrogenation Emulsifier EL-60 and
One or more of Emulsifier EL-60.
4. according to claim 1 or 2 for preventing and treating the molecule micro emulsion of chicken leucocyte protozoon, which is characterized in that institute
The solvent stated is selected from one or more of glacial acetic acid, ethyl alcohol, water and dimethyl acetamide.
5. according to claim 1 or 2 for preventing and treating the molecule micro emulsion of chicken leucocyte protozoon, which is characterized in that institute
The antioxidant stated is selected from one or more of BHA, BHT and propylgallate.
6. according to claim 1 or 2 for preventing and treating the molecule micro emulsion of chicken leucocyte protozoon, which is characterized in that institute
The preservative stated is selected from one or more of EDTA, benzoic acid, sodium benzoate and potassium sorbate.
7. it is of any of claims 1-6 for preventing and treating the preparation method of the molecule micro emulsion of chicken leucocyte protozoon,
Characterized by comprising the following steps:
(1) each component is weighed in parts by weight；
(2) pyrimethamine is dissolved using solvent, obtains pyrimethamine solution；
(3) antioxidant and preservative are dissolved using solvent respectively, obtain antioxidant solution and antiseptic solution；
(4) by emulsifier heating and melting, the pyrimethamine solution in step (2) and astragalus polyose stirring is added, obtains emulsion；
(5) antioxidant solution obtained by emulsion obtained by step (4) and step (3) and antiseptic solution are mixed, micropore
Membrane filtration is to get the molecule micro emulsion for preventing and treating chicken leucocyte protozoon.
8. preparation method according to claim 7, which is characterized in that in step (2), the weight ratio of pyrimethamine and solvent
For 1:1-10, in step (3), the weight ratio of antioxidant and solvent is 1:1-5；The weight ratio of preservative and solvent is 1:1-3.
9. preparation method according to claim 7, which is characterized in that in step (4), the heating and melting temperature be 60~
120 DEG C, the specific steps of pyrimethamine solution and astragalus polyose are added are as follows: in the state of heating, pyrimethamine solution is added
With astragalus polyose stirring until all melting；The time stirred after addition are as follows: 30-60min.
10. preparation method according to claim 7, which is characterized in that in step (5), be dispersed with stirring with high-speed homogenization machine
10-30min, using 100-300nm filtering with microporous membrane.
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