CN105998036A - Compound sulfa-nitazoxanide soluble powder for pigs and poultry - Google Patents

Compound sulfa-nitazoxanide soluble powder for pigs and poultry Download PDF

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Publication number
CN105998036A
CN105998036A CN201610353200.4A CN201610353200A CN105998036A CN 105998036 A CN105998036 A CN 105998036A CN 201610353200 A CN201610353200 A CN 201610353200A CN 105998036 A CN105998036 A CN 105998036A
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sodium
nitazoxanide
mixture
soluble powder
grams
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CN201610353200.4A
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CN105998036B (en
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胡涵
张义仁
魏迎军
李润乐
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Luoyang Veterinary Medicines Factory
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Luoyang Veterinary Medicines Factory
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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
    • A61K31/63—Compounds containing para-N-benzenesulfonyl-N-groups, e.g. sulfanilamide, p-nitrobenzenesulfonyl hydrazide
    • A61K31/635—Compounds containing para-N-benzenesulfonyl-N-groups, e.g. sulfanilamide, p-nitrobenzenesulfonyl hydrazide having a heterocyclic ring, e.g. sulfadiazine
    • 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
    • A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
    • A61K31/425—Thiazoles
    • A61K31/426—1,3-Thiazoles
    • 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
    • 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
    • A61K9/0087—Galenical forms not covered by A61K9/02 - A61K9/7023
    • A61K9/0095—Drinks; Beverages; Syrups; Compositions for reconstitution thereof, e.g. powders or tablets to be dispersed in a glass of water; Veterinary drenches
    • 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
    • A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
    • A61K9/141—Intimate drug-carrier mixtures characterised by the carrier, e.g. ordered mixtures, adsorbates, solid solutions, eutectica, co-dried, co-solubilised, co-kneaded, co-milled, co-ground products, co-precipitates, co-evaporates, co-extrudates, co-melts; Drug nanoparticles with adsorbed surface modifiers
    • A61K9/145—Intimate drug-carrier mixtures characterised by the carrier, e.g. ordered mixtures, adsorbates, solid solutions, eutectica, co-dried, co-solubilised, co-kneaded, co-milled, co-ground products, co-precipitates, co-evaporates, co-extrudates, co-melts; Drug nanoparticles with adsorbed surface modifiers with organic compounds

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

The invention provides compound sulfa-nitazoxanide soluble powder for pigs and poultry. The soluble powder is prepared from the following components: 20-30g of sulfa-drugs, 4-10.0g of TMP sodium, 1.5-5g of nitazoxanide, 5-25g of a co-solvent and 1-7.5g of a stabilizing agent, and the total amount after the components and auxiliaries are mixed is 100g. The soluble powder can be used for overcoming the defect that sulfa-drugs are invalid to anaerobic bacteria during infection of coccidium mixed with anaerobic bacteria, has excellent effects in preventing and treating protozoon infection and mixed infection of protozoon and bacteria of pigs and poultry, and is valid to drug-resistance coccidium infection which is poor or invalid to sulfa-drugs; nitazoxanide has the defects of water insolubility and alkali solubility, while the co-solvent can be used for improving the water solubility of nitazoxanide, and the stability of nitazoxanide can be improved by adding the stabilizing agent. The compound sulfa-nitazoxanide soluble powder is administrated by drinking, is convenient to use, and has excellent effects on preventing and treating protozoon infection and mixed infection of protozoa and bacteria of pigs and poultry.

Description

One boar fowl compound sulfonamide nitazoxanide soluble powder
Technical field
The present invention relates to the medicine of veterinary drug technical field, especially one boar fowl compound sulfonamide nitazoxanide soluble powder.
Background technology
Sulfonamides belongs to chemosynthesis broad-spectrum antibacterial agent, water insoluble, is soluble in alkaline solution.Existing medicine by with to amino Benzoic acid competition dihydrofolate synthetase, thus hinder the synthesis of sensitive organism folic acid and play bacteriostasis.Higher mammal can be directly Utilize exogenous folic acid, therefore its metabolism is not disturbed by sulfa drugs.To most of gram positive bacterias and part Gram-negative Bacterium is effective, and coccidiosis, chicken are lived coccidium syphilidis, toxoplasma etc. also effectively, but to spirillum, rickettsia, tubercule bacillus etc. Without effect.Being widely used through for many years, because of reasons such as dosage and the deficiencies course for the treatment of, antibacterial, coccidiosis easily produce drug resistance to sulfonamides, Especially being easily generated most with staphylococcus, escherichia coli, streptococcus etc. take second place.After antibacterial, coccidiosis produce drug resistance to a kind of sulfanilamide, Other sulfonamides also can be produced cross resistance in various degree.Above sulfonamides resistance problems and antibacterial, protozoacide Spectrum is the most not enough.
In view of the foregoing, a boar fowl compound sulfonamide nitazoxanide soluble powder is now developed.
Summary of the invention
The invention aims to overcome deficiency of the prior art, it is provided that boar fowl compound sulfonamide nitazoxanide solubility Powder, can overcome the disadvantages that the shortcoming that when coccidiosis mixing anaerobic bacterium infects, sulphonamides is invalid to anaerobe, has prevention and treatment pig fowl protozoon sense Dye and the good action of protozoon and bacteria mixed infection, the drug resistance coccidium infection poor or invalid to sulphonamides curative effect is effective, nitre The shortcoming of azoles nit is to be insoluble in water, is soluble in alkali, and cosolvent, to improve its water solublity, adds stabilizer and improves its stability, By drinking water administration, easy to use, preventing and treat pig fowl protozoan infection and protozoon has good result with bacteria mixed infection.
The present invention to achieve these goals, adopts the following technical scheme that a boar fowl compound sulfonamide nitazoxanide soluble powder, By the preparation synthesis of following component: sulphonamides 20～30 grams, TMP sodium 4～10.0 grams, nitazoxanide 1.5～5 grams, cosolvent 5～ 25 grams, stabilizer 1～7.5 grams, above component are 100 grams with the mixed total amount of adjuvant.
Described sulphonamides is sulfamonomethoxine sodium or sulfameter sodium or Sulfaquinoxaline sodium or nefrosulfin Pyrazine sodium, one or more combination therein.
Described cosolvent is sodium citrate or sodium carbonate or sodium benzoate or potassium carbonate or meglumine, one therein Or several combinations.
Described stabilizer is selected from EDTA2 sodium or calcium disodium edetate or sodium tripolyphosphate or sodium sulfite, therein one Kind or several combinations.
Described adjuvant is selected from glucose or lactose or sucrose or water soluble starch or anhydrous sodium sulfate or bicarbonate Sodium or benefit powder or auxiliary U.S. powder, one or more combination therein.
The first step, by described nitazoxanide and described cosolvent mixing and stirring in the way of being incremented by step by step, obtains mixture A, Again prepared mixture A is added in described sulphonamides obtain mixture B, standby；
Second step, obtains mixture C by described stabilizer and described TMP sodium mixing and stirring, then prepared mixture C It is stirred at room temperature uniformly with mixture B, prepares mixture D, standby；Finally prepared mixture D is added in adjuvant It is uniformly mixed under room temperature, prepares mixture E, standby；
3rd step, directly sieves prepared mixture E or grinding and sieving, and screen cloth uses 60～80 mesh sieves, by 50g～1000g It is sub-packed in packaging bag or Packaging Bottle, after sealing or gland, prepares finished product.
The invention has the beneficial effects as follows: trimethoprim sodium (TMP sodium), have another name called trimethoprim sodium, trimethoprim sodium, For white or slightly yellow crystalline powder, mildly bitter flavor, dissolve in water, this product pharmacological action is broad spectrum antibiotic, antimicrobial spectrum with Sulfa drugs seemingly, has the effect of suppression dihydrofolate reductase, but antibacterial is relatively easily generated drug resistance, is seldom used alone.With sulphur Amine medicine share, and the folic acid metabolism of antibacterial can be made by double blocking, thus antibacterial action increases substantially, and can strengthen by antibacterial action Several times to tens times, therefore have the title of trimethoprim (TMP), and the appearance of drug resistance strain can be reduced.TMP sodium as antibacterial synergist, Main share the ratio use of 1: 5 or 1: 3 (typically by) with sulphonamides and can make that sulphonamides is antibacterial, protozoacide effect enhancing number Times to decades of times, septicemia that poultry escherichia coli cause, Pullorum Disease, avian typhoid, cholera, respiratory system Secondary cases can be treated Antibacterial infection etc..Can be additionally used in the preventing and treating of coccidiosis.This product oral absorption is complete, up to more than the 90% of dosage, after absorption Being widely distributed in tissue and the body fluid of whole body, may pass through blood brain barrier, when meninges inflammation, cerebrospinal fluid drug level is up to blood The 50%～100% of liquid concentration, may pass through Placenta Hominis and enters in fetus body, and fetal circulation blood drug level is close with parent blood concentration, should Product are mainly through renal excretion, and during 24h urinates, output is the 40%～60% of dosage: wherein 80%～90% discharge with medicine original shape, These product t1/2 is 8～10h.
Feature 1: the present invention selects TMP sodium to make synergist, and the advantage of relatively TMP is, soluble in water, is more suitable for powder and mixes Drink is administered, and this product is alkalescence, is more suitable for the synergist as sulphonamides.
Nitazoxanide (nitazoxanide, NTZ) is a kind of nitrothiazole amino benzenes compounds, has broad-spectrum disease resistance substance activity, To parasite, protozoon, antibacterial and virus effectively.Specifically include the protozoon of intraor extracellular, anthelmintic, anaerobe, and virus. Activity in vivo is relevant with its deacetylation derivative tizoxanide (tizoxanide, T).
Feature 2: the feature of above a few class drug combinations is that nitazoxanide can strengthen the protozoacide effect of sulphonamides, can overcome the disadvantages that ball The shortcoming that when worm mixing anaerobic bacterium infects, sulphonamides is invalid to anaerobe, has prevention and treatment pig fowl protozoan infection and protozoon with thin The good action of bacterium mixed infection, the diarrhoea etc. caused such as pig fowl coccidiosis.The soluble powder of the present invention, poor to sulphonamides curative effect Or invalid drug resistance coccidium infection is effective.The shortcoming of nitazoxanide is to be insoluble in water, is soluble in alkali, and the present invention adds suitable Cosolvent is to improve its water solublity, and adds stabilizer to improve its stability.The soluble powder of the present invention, by drinking water administration, Easy to use, it is used for preventing and treat pig fowl protozoan infection and protozoon and bacteria mixed infection, all has good result.
Detailed description of the invention
The present invention is described in further detail with detailed description of the invention below in conjunction with embodiment:
Embodiment 1
The first step, by nitazoxanide and sodium carbonate mixing and stirring in the way of being incremented by step by step, obtains mixture A, then system The mixture A obtained is added in sulfamonomethoxine sodium obtain mixture B, standby；
Second step, obtains mixture C by EDTA2 sodium and TMP sodium mixing and stirring, then prepared mixture C with mixed Compound B is stirred at room temperature uniformly, prepares mixture D, standby；Finally prepared mixture D is added in adjuvant in room temperature Under be uniformly mixed, prepare mixture E, standby；
3rd step, directly sieves prepared mixture E or grinding and sieving, and screen cloth uses 60～80 mesh sieves, divides by 100g It is loaded in packaging bag, after sealing, prepares finished product.
Embodiment 2
The first step, by nitazoxanide and sodium benzoate mixing and stirring in the way of being incremented by step by step, obtains mixture A, then The mixture A prepared is added in sulfameter sodium obtain mixture B, standby；
Second step, obtains mixture C by sodium sulfite and TMP sodium mixing and stirring, then prepared mixture C with mix Thing B is stirred at room temperature uniformly, prepares mixture D, standby；Finally prepared mixture D is added in adjuvant at room temperature It is uniformly mixed, prepares mixture E, standby；
3rd step, directly sieves prepared mixture E or grinding and sieving, and screen cloth uses 60～80 mesh sieves, divides by 150g It is loaded in Packaging Bottle, after gland, prepares finished product.
Embodiment 3
The first step, by nitazoxanide and sodium citrate mixing and stirring in the way of being incremented by step by step, obtains mixture A, then The mixture A prepared is added in sulfaclozine sodium obtain mixture B, standby；
Second step, obtains mixture C by calcium disodium edetate and TMP sodium mixing and stirring, then prepared mixture C with mixed Compound B is stirred at room temperature uniformly, prepares mixture D, standby；Finally prepared mixture D is added in adjuvant in room temperature Under be uniformly mixed, prepare mixture E, standby；
3rd step, directly sieves prepared mixture E or grinding and sieving, and screen cloth uses 60～80 mesh sieves, divides by 200g It is loaded in packaging bag, after sealing, prepares finished product.

Claims (6)

1. boar fowl compound sulfonamide nitazoxanide soluble powder, it is characterised in that: by the preparation synthesis of following component: sulphonamides 20～30 grams, TMP sodium 4～10.0 grams, nitazoxanide 1.5～5 grams, cosolvent 5～25 grams, stabilizer 1～7.5 grams, Above component and the mixed total amount of adjuvant are 100 grams.
Boar fowl compound sulfonamide nitazoxanide soluble powder the most according to claim 1, it is characterised in that: described Sulphonamides is sulfamonomethoxine sodium or sulfameter sodium or Sulfaquinoxaline sodium or sulfaclozine sodium, its In the combination of one or more.
Boar fowl compound sulfonamide nitazoxanide soluble powder the most according to claim 1, it is characterised in that: described Cosolvent is sodium citrate or sodium carbonate or sodium benzoate or potassium carbonate or meglumine, one or more group therein Close.
Boar fowl compound sulfonamide nitazoxanide soluble powder the most according to claim 1, it is characterised in that: described Stabilizer is selected from EDTA2 sodium or calcium disodium edetate or sodium tripolyphosphate or sodium sulfite, therein one or more Combination.
Boar fowl compound sulfonamide nitazoxanide soluble powder the most according to claim 1, it is characterised in that: described Adjuvant is selected from glucose or lactose or sucrose or water soluble starch or anhydrous sodium sulfate or sodium bicarbonate or benefit Powder or auxiliary U.S. powder, one or more combination therein.
6. the boar fowl preparation method of compound sulfonamide nitazoxanide soluble powder, it is characterised in that:
The first step, by described nitazoxanide and described cosolvent mixing and stirring in the way of being incremented by step by step, obtains mixture A, Again prepared mixture A is added in described sulphonamides obtain mixture B, standby；
Second step, obtains mixture C by described stabilizer and described TMP sodium mixing and stirring, then prepared mixture C It is stirred at room temperature uniformly with mixture B, prepares mixture D, standby；Finally prepared mixture D is added in adjuvant It is uniformly mixed under room temperature, prepares mixture E, standby；
3rd step, directly sieves prepared mixture E or grinding and sieving, and screen cloth uses 60～80 mesh sieves, by 50g～1000g It is sub-packed in packaging bag or Packaging Bottle, after sealing or gland, prepares finished product.
CN201610353200.4A 2016-05-19 2016-05-19 One boar fowl compound sulfonamide Nitazoxanide soluble powder Active CN105998036B (en)

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Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN111012788A (en) * 2019-12-12 2020-04-17 武汉职业技术学院 Application of nitazoxanide and tizoxanide in preparation of medicine for resisting porcine reproductive and respiratory syndrome virus
CN112826797A (en) * 2021-01-14 2021-05-25 四川恒通动保生物科技有限公司 Novel compound anti-coccidium soluble powder and preparation method thereof

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN103585163A (en) * 2013-11-06 2014-02-19 青岛农业大学 Veterinary drug for treating chicken coccidiosis
CN103648282A (en) * 2011-05-16 2014-03-19 罗马克实验室有限公司 Use of thiazolide compounds for the prevention and treatment of viral diseases, cancer and diseases caused by intracellular infections
CN105213402A (en) * 2015-09-30 2016-01-06 洛阳市兽药厂 A kind of poultry compound enrofloxacin meloxicam soluble powder

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN103648282A (en) * 2011-05-16 2014-03-19 罗马克实验室有限公司 Use of thiazolide compounds for the prevention and treatment of viral diseases, cancer and diseases caused by intracellular infections
CN103585163A (en) * 2013-11-06 2014-02-19 青岛农业大学 Veterinary drug for treating chicken coccidiosis
CN105213402A (en) * 2015-09-30 2016-01-06 洛阳市兽药厂 A kind of poultry compound enrofloxacin meloxicam soluble powder

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
刁有祥: "《鸡场用药手册》", 31 March 2014, 金盾出版社 *

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN111012788A (en) * 2019-12-12 2020-04-17 武汉职业技术学院 Application of nitazoxanide and tizoxanide in preparation of medicine for resisting porcine reproductive and respiratory syndrome virus
CN111012788B (en) * 2019-12-12 2021-01-15 武汉职业技术学院 Application of nitazoxanide and tizoxanide in preparation of medicine for resisting porcine reproductive and respiratory syndrome virus
CN112826797A (en) * 2021-01-14 2021-05-25 四川恒通动保生物科技有限公司 Novel compound anti-coccidium soluble powder and preparation method thereof

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