CN106539754A - Hydrobromic acid antifebrile dichroanone solution and preparation method thereof - Google Patents
Hydrobromic acid antifebrile dichroanone solution and preparation method thereof Download PDFInfo
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- CN106539754A CN106539754A CN201611053242.2A CN201611053242A CN106539754A CN 106539754 A CN106539754 A CN 106539754A CN 201611053242 A CN201611053242 A CN 201611053242A CN 106539754 A CN106539754 A CN 106539754A
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- hydrobromic acid
- acid antifebrile
- antifebrile dichroanone
- dichroanone
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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
- A61K31/517—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with carbocyclic ring systems, e.g. quinazoline, perimidine
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- 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
- A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
- A61K47/10—Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
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- 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
- A61K47/16—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing nitrogen, e.g. nitro-, nitroso-, azo-compounds, nitriles, cyanates
- A61K47/18—Amines; Amides; Ureas; Quaternary ammonium compounds; Amino acids; Oligopeptides having up to five amino acids
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- 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
- A61K47/20—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing sulfur, e.g. dimethyl sulfoxide [DMSO], docusate, sodium lauryl sulfate or aminosulfonic acids
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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
- A61K9/08—Solutions
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Abstract
The invention discloses a kind of hydrobromic acid antifebrile dichroanone solution, it is equipped with dimethyl acetylamide, antioxidant, dimethyl sulfoxide and PEG400 with hydrobromic acid antifebrile dichroanone as major ingredient, the compatibility of dispensing is reasonable, made hydrobromic acid antifebrile dichroanone stability of solution is good, and bioavailability is high, and drug effect is notable；The invention also discloses the preparation method of hydrobromic acid antifebrile dichroanone solution, simply, process is easily controllable, with short production cycle, is adapted to industrialized production for the method.The present invention is suitable for preparing hydrobromic acid antifebrile dichroanone solution.
Description
Technical field
The invention belongs to pharmaceutical formulating art, is related to a kind of hydrobromic acid antifebrile dichroanone solution and preparation method thereof.
Background technology
Chicken coccidiosis are a kind of Protozool diseases very harmful to poultry husbandry, and cause of disease is mainly including Eimeria tenella
(E. tenella) and Eimeria Necatrix (E.necatrix) etc..After Chickens Infected coccidiosiss, a large amount of enterocytes are impaired,
Bleeding, severe patient are dead.Intensive culture factory is the optimum place of coccidiosis outburst, and its case fatality rate is sometime up to 40%.
The medicine of existing treatment coccidiosiss is a lot, is essentially all chemical drugss composition, due to chemical drugss metabolism in vivo
The time of some is needed, and life-time service chemicalses are easily accumulated in carcasses, limit its application.Halofuginone hydrobromide is therefrom
Various coccidiosiss are had suppression to kill effect by the effective ingredient extracted in medical material Radix Dichroae, especially tender to chicken, murder by poisoning, huge Amy ear
Coccidiosiss are especially sensitive.Product in the market mostly is hydrobromic acid antifebrile dichroanone pre-mixing agent, it is impossible to drinks for poultry, is only used for
Spice, and there is the uneven phenomenon of stirring during spice, the cultivation factory of particulate material is not suitable in addition yet, is limited pre-
The use of mixture, is not suitable for animal husbandry application.
The content of the invention
The technical problem to be solved in the present invention, is to provide a kind of hydrobromic acid antifebrile dichroanone solution, based on hydrobromic acid antifebrile dichroanone
Material, is also equipped with dimethyl acetylamide, antioxidant, dimethyl sulfoxide and PEG400, and the compatibility of dispensing is rationally, made
Hydrobromic acid antifebrile dichroanone stability of solution is good, and drug effect is notable.
Another object of the present invention, there is provided the preparation method of above-mentioned hydrobromic acid antifebrile dichroanone solution, the method letter
Single, process is easily controllable, with short production cycle, is adapted to industrialized production.
To solve above-mentioned technical problem, the technical solution used in the present invention is：
A kind of hydrobromic acid antifebrile dichroanone solution, in parts by weight it include following component：
Hydrobromic acid antifebrile dichroanone 0.6～3,
Dimethyl acetylamide 25～50,
Antioxidant 0.01～0.05,
Dimethyl sulfoxide 10～20,
PEG400 30～50.
As the restriction of the present invention：
The antioxidant is the one kind in BHA, BHT, PG, TBHQ or TP；
The antioxidant compares 1 according to weight for any two kinds in BHA, BHT, PG, TBHQ and TP:1 compounding.
Present invention also offers the preparation method of hydrobromic acid antifebrile dichroanone solution, it is carried out according to steps order：
（1）Dimethyl acetylamide and dimethyl sulfoxide mix homogeneously are taken, solution a is obtained；
（2）Take hydrobromic acid antifebrile dichroanone and be dissolved in solution a, and be added thereto to antioxidant, mix homogeneously obtains solution b；
（3）To in solution b, add PEG400, constant volume to obtain hydrobromic acid antifebrile dichroanone solution.
Hydrobromic acid antifebrile dichroanone can be very without the need for heating in being dissolved in DMAC N,N' dimethyl acetamide and dimethyl sulfoxide mixed solution
Fast thorough dissolving；Antioxidant is added to make hydrobromic acid antifebrile dichroanone solution content stable, color and luster will not be deepened；Prepared with this technique
Clarity of solution it is good, lighter color, stable content are uniform.All solvents are mixed into step dissolving hydrobromic acid antifebrile dichroanone, hydrogen bromine such as
Sour halofuginone hydrobromide dissolving is slow, needs heating for dissolving, heating easily to cause medicinal liquid color burn, content slightly to drop, therefore dissolves what is prepared step by step
Hydrobromic acid antifebrile dichroanone solution is better than the stability of a step mixed dissolution.
As a result of above-mentioned technical scheme, compared with prior art, acquired technological progress is the present invention：
The hydrobromic acid antifebrile dichroanone solution that the present invention is provided, rationally, the dissolution rate of medicine is improved the compatibility of dispensing, made hydrobromic acid
Halofuginone hydrobromide stability of solution is good, and significantly, bioavailability is improved drug effect, noresidue, does not produce drug resistance, and clinical practice is convenient；
The preparation method of the above-mentioned hydrobromic acid antifebrile dichroanone solution that the present invention is provided is simple, and process is easily controllable, with short production cycle, fits
Should be in industrialized production.
The present invention is suitable for preparing hydrobromic acid antifebrile dichroanone solution.
The present invention is described in further detail below in conjunction with specific embodiment.
Specific embodiment
The preparation method of 1 hydrobromic acid antifebrile dichroanone solution of embodiment
The present embodiment is a kind of preparation method of hydrobromic acid antifebrile dichroanone solution, and it is carried out successively according to steps order：
（11）25kg dimethyl acetylamide and 15kg dimethyl sulfoxide mix homogeneously are taken, solution a1 is obtained；
（12）Take 0.9kg hydrobromic acid antifebrile dichroanones and be dissolved in solution a1, and be added thereto to 0.03kg antioxidant TP, mix homogeneously,
Obtain solution b1；
（13）To in solution b1, add 44kg PEG400s, constant volume to obtain hydrobromic acid antifebrile dichroanone solution.
The present embodiment preparation method is simple, and process is easily controllable, the dissolution of prepared hydrobromic acid antifebrile dichroanone drug in solution
Rate is improved, and made hydrobromic acid antifebrile dichroanone stability of solution is good, and significantly, bioavailability is improved drug effect, noresidue, do not produce it is resistance to
The property of medicine, clinical practice are convenient.
The preparation method of embodiment 2-6 hydrobromic acid antifebrile dichroanone solution
Embodiment 2-6 is respectively a kind of preparation method of hydrobromic acid antifebrile dichroanone solution, and preparation process is same as Example 1, different
Part is only that：The consumption of dispensing is different.1 is shown in Table specifically.
Embodiment 2-6 preparation method is simple, and process is easily controllable, the dissolution of prepared hydrobromic acid antifebrile dichroanone drug in solution
Rate is improved, and made hydrobromic acid antifebrile dichroanone stability of solution is good, and significantly, bioavailability is improved drug effect, noresidue, do not produce it is resistance to
The property of medicine, clinical practice are convenient.
The preparation method of embodiment 7-10 hydrobromic acid antifebrile dichroanone solution
Embodiment 7-10 is respectively a kind of formula of the preparation method preparation process and correlation of hydrobromic acid antifebrile dichroanone solution and implements
Example 1 is identical, the difference is that only：The species of antioxidant is different, the antioxygen used by each embodiment in embodiment 7-10
It is 1 according to weight ratio that agent is two kinds of different antioxidants:1 carries out compounding the Compositional type antioxidant of formation, specially：Implement
The antioxidant of example 7 is BHA and TBHQ, and the antioxidant of embodiment 8 is BHT and PG, the antioxidant of embodiment 9 be TP and
BHT, the antioxidant of embodiment 10 is BHA and PG.
The contrast test of 11 hydrobromic acid antifebrile dichroanone solution of embodiment
The present embodiment is molten with hydrobromic acid antifebrile dichroanone prepared by the present embodiment 1 from hydrobromic acid antifebrile dichroanone pre-mixing agent of the prior art
Liquid carries out contrast test.
Experimentation：
The AA broiler of 10 ages in days of 200 health that physically well develop, every chicken 0.5ml is selected to be contained within Eimeria tenella Sporulated
2.0 × 105 suspension per oral inoculation of egg capsule in crop is spoken in a low voice is randomly divided into 4 groups, is followed successively by hydrobromic acid antifebrile dichroanone pre-mixing agent, hydrobromic acid
Halofuginone hydrobromide solution, positive controls and blank control group.
Symptom：After counteracting toxic substances, there is subtracting food, lassitude, slow-witted vertical, feather and towers in chickling；Diarrhoea is in water sample, around cloacal aperture
Feather is drained thing pollution, adhesion；Then gradually become thin, cockscomb wattle is pale, feces are coffee-like or hemafecia, dipteron paresis, walk
Road is lacked of proper care, and crop is hydraulically full, refusing to eat, dead 10.
Therapeutic test result：
Statistics is cutd open at the end of first 3 days, 4 days heel row insect pest situation conditions of administration and experiment is administered and kills detection polypide residual condition, calculates essence
Meter deworming rates, rough anthelminthic rate, the net rate of drive, refer to table 2.
Essence meter deworming rates=（The worm's ovum number after worm's ovum number-administration before administration）Worm's ovum number × 100% before/administration.
Rough anthelminthic rate：（Matched group averagely remains polypide number-test group and averagely remains polypide number）/ matched group is averagely residual
Stay polypide number × 100%.
Drive net rate：Drive percent × 100% of the chicken number/total Test chicken number of net polypide.
Conclusion：
Clinical effectiveness shows that hydrobromic acid antifebrile dichroanone has preferable curative effect to the coccidiosis of chicken, due to hydrobromic acid antifebrile dichroanone pre-mixing agent not
Water can be dissolved in, it is necessary to mix in feedstuff, chicken fall ill it is latter as can all cause feed intake to decline, so pre-mixing agent is it cannot be guaranteed that per only
Chicken can search for food enough medicines, and therapeutic effect does not have hydrobromic acid antifebrile dichroanone solution preferable.Hydrobromic acid antifebrile dichroanone solution its drive
Worm rate, rough anthelminthic rate and the net rate of drive show the effect of preventing and treating, determined curative effect, economical rationality, and have no toxic side effect.This
Dosage form solutions agent in bright is better than pre-mixing agent in terms for the treatment of coccidiosiss effect.
Embodiment 1-10, is only presently preferred embodiments of the present invention, is not other forms made for the present invention
Limit, any those skilled in the art are changed as enlightenment possibly also with above-mentioned technology contents or are modified as equivalent
The Equivalent embodiments of change.In every case it is the technical spirit without departing from the claims in the present invention, to the letter done by above example
Single modification, equivalent variations and remodeling, still fall within the scope of the claims in the present invention protection.
Claims (4)
1. a kind of hydrobromic acid antifebrile dichroanone solution, it is characterised in that it includes following component in parts by weight：
Hydrobromic acid antifebrile dichroanone 0.6～3,
Dimethyl acetylamide 25～50,
Antioxidant 0.01～0.05,
Dimethyl sulfoxide 10～20,
PEG400 30～50.
2. hydrobromic acid antifebrile dichroanone solution according to claim 1, it is characterised in that：The antioxidant be BHA, BHT,
One kind in PG, TBHQ or TP.
3. hydrobromic acid antifebrile dichroanone solution according to claim 1, it is characterised in that：The antioxidant be BHA, BHT,
Any two kinds in PG, TBHQ and TP compare 1 according to weight:1 compounding.
4. a kind of preparation method of the hydrobromic acid antifebrile dichroanone solution as described in any one in claim 1-3, it is characterised in that
It is carried out according to steps order：
（1）Dimethyl acetylamide and dimethyl sulfoxide mix homogeneously are taken, solution a is obtained；
（2）Take hydrobromic acid antifebrile dichroanone and be dissolved in solution a, and be added thereto to antioxidant, mix homogeneously obtains solution b；
（3）To in solution b, add PEG400, constant volume to obtain hydrobromic acid antifebrile dichroanone solution.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201611053242.2A CN106539754A (en) | 2016-11-25 | 2016-11-25 | Hydrobromic acid antifebrile dichroanone solution and preparation method thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201611053242.2A CN106539754A (en) | 2016-11-25 | 2016-11-25 | Hydrobromic acid antifebrile dichroanone solution and preparation method thereof |
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| CN106539754A true CN106539754A (en) | 2017-03-29 |
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| CN201611053242.2A Pending CN106539754A (en) | 2016-11-25 | 2016-11-25 | Hydrobromic acid antifebrile dichroanone solution and preparation method thereof |
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110731943A (en) * | 2019-10-15 | 2020-01-31 | 河南牧翔动物药业有限公司 | halofuginone hydrobromide soluble powder and its preparation method |
| CN114288300A (en) * | 2022-01-29 | 2022-04-08 | 中国科学技术大学 | Application of halofuginone in medicine for treating and preventing fatty liver and obesity |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2003070153A2 (en) * | 2002-02-21 | 2003-08-28 | Collgard Biopharmaceuticals Ltd. | Stabilized pharmaceutical compositions of halofuginone and other quinazolinone derivatives |
| CN104640546A (en) * | 2012-03-29 | 2015-05-20 | 哈龙医疗有限责任公司 | Dosage forms of halofuginone and methods of use |
-
2016
- 2016-11-25 CN CN201611053242.2A patent/CN106539754A/en active Pending
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2003070153A2 (en) * | 2002-02-21 | 2003-08-28 | Collgard Biopharmaceuticals Ltd. | Stabilized pharmaceutical compositions of halofuginone and other quinazolinone derivatives |
| CN104640546A (en) * | 2012-03-29 | 2015-05-20 | 哈龙医疗有限责任公司 | Dosage forms of halofuginone and methods of use |
Non-Patent Citations (1)
| Title |
|---|
| 王贤玉: "抗球虫药氢溴酸常山酮的研究进展", 《养禽与禽病防治》 * |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110731943A (en) * | 2019-10-15 | 2020-01-31 | 河南牧翔动物药业有限公司 | halofuginone hydrobromide soluble powder and its preparation method |
| CN110731943B (en) * | 2019-10-15 | 2022-02-08 | 河南牧翔动物药业有限公司 | Febuxostat hydrobromide soluble powder and preparation method thereof |
| CN114288300A (en) * | 2022-01-29 | 2022-04-08 | 中国科学技术大学 | Application of halofuginone in medicine for treating and preventing fatty liver and obesity |
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Application publication date: 20170329 |