CN105998036B - One boar fowl compound sulfonamide Nitazoxanide soluble powder - Google Patents
One boar fowl compound sulfonamide Nitazoxanide soluble powder Download PDFInfo
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- CN105998036B CN105998036B CN201610353200.4A CN201610353200A CN105998036B CN 105998036 B CN105998036 B CN 105998036B CN 201610353200 A CN201610353200 A CN 201610353200A CN 105998036 B CN105998036 B CN 105998036B
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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
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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
- A61K31/41—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
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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
- 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
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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
- A61K9/14—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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Abstract
One boar fowl compound sulfonamide Nitazoxanide soluble powder is synthesized by the preparation of following component：20~30 grams of sulfa drug, 4~10.0 grams of TMP sodium, 1.5~5 grams of Nitazoxanide, 5~25 grams of cosolvent, 1~7.5 gram of stabilizer, the above component and the mixed total amount of auxiliary material are 100 grams；The sulfa drug disadvantage invalid to anaerobic bacteria when can overcome the disadvantages that the infection of coccidia mixing anaerobic bacterium, good action with prevention and treatment pig fowl protozoan infection and protozoon and bacteria mixed infection, drug resistance coccidium infection poor to sulfa drug curative effect or invalid is effective, the shortcomings that Nitazoxanide is to be insoluble in water, it is soluble in alkali, cosolvent is to improve its water solubility, stabilizer is added to improve its stability, pass through drinking water administration, easy to use, preventing and treating the protozoan infection of pig fowl and protozoon and bacteria mixed infection has good result.
Description
Technical field
It is soluble with compound sulfonamide Nitazoxanide that the present invention relates to the drug of veterinary drug technical field, especially a boar fowl
Powder.
Background technology
Sulfamido belongs to chemical synthesis broad-spectrum antibacterial agent, not soluble in water, is soluble in alkaline solution.Existing drug by with it is right
Aminobenzoic acid competes dihydrofolate synthetase, and bacteriostasis is played to hinder the synthesis of sensitive bacteria folic acid.Higher mammal
Exogenous folic acid can be directly utilized, therefore its metabolism is not interfered by sulfa drugs.Most of gram-positive bacterias and part are removed from office
Lan Shi negative bacteriums are effective, live coccidium syphilidis, toxoplasma etc. also effectively to coccidia, chicken, but to conveyor screw, rickettsia, tuberculosis
Bacillus etc. is without effect.By being widely used for many years, because of the reasons such as dosage and course for the treatment of deficiency, bacterium, coccidia easily generate sulfamido
Drug resistance is most also easy to produce with staphylococcus especially, and Escherichia coli, streptococcus etc. take second place.Bacterium, coccidia generate drug resistance to a kind of sulfanilamide (SN)
After property, different degrees of cross resistance can also be generated to other sulfonamides.The above sulfamido resistance problems and antibacterial,
Antiprotozoan spectrum is insufficient.
In view of the foregoing, boar fowl compound sulfonamide Nitazoxanide soluble powder is now developed.
Invention content
Purpose of the invention is to overcome the shortcomings in the prior art, provides a boar fowl compound sulfonamide Nitazoxanide
Soluble powder, the sulfa drug disadvantage invalid to anaerobic bacteria when can overcome the disadvantages that the infection of coccidia mixing anaerobic bacterium have prevention and treatment pig
The good action of fowl protozoan infection and protozoon and bacteria mixed infection, drug resistance coccidia sense poor to sulfa drug curative effect or invalid
It is infected with effect, the shortcomings that Nitazoxanide is to be insoluble in water, is soluble in alkali, stabilizer is added to carry to improve its water solubility in cosolvent
Its high stability, easy to use by drinking water administration, prevent and treat the protozoan infection of pig fowl and protozoon has with bacteria mixed infection
Good result.
The present invention to achieve the goals above, adopts the following technical scheme that：One boar fowl can with compound sulfonamide Nitazoxanide
Dissolubility powder is synthesized by the preparation of following component：20~30 grams of sulfa drug, 4~10.0 grams of TMP sodium, 1.5~5 grams of Nitazoxanide, hydrotropy
5~25 grams of agent, 1~7.5 gram of stabilizer, the above component and the mixed total amount of auxiliary material are 100 grams.
The sulfa drug is Sulfamonomethoxime Sodium or 5-methoxysulfadiazine sodium or Embazin or sulphur
Amine chloropyrazine sodium, one such or several combination.
The cosolvent is sodium citrate or sodium carbonate or sodium benzoate or potassium carbonate or meglumine, therein one
Kind or several combinations.
The stabilizer is to be selected from EDTA2 sodium or mosatil or sodium tripolyphosphate or sodium sulfite, therein
One or more of combinations.
The auxiliary material is selected from glucose or lactose or sucrose or water soluble starch or anhydrous sodium sulfate or carbonic acid
Hydrogen sodium or benefit powder or auxiliary U.S. powder, one such or several combination.
The Nitazoxanide and the cosolvent are mixed evenly in a manner of incremental step by step, are mixed by the first step
Object A is closed, then mixture A obtained is added in the sulfa drug and obtains mixture B, it is spare；
Second step is mixed evenly the stabilizer and the TMP sodium to obtain mixture C, then mixing obtained
Object C and mixture B is stirred at room temperature uniformly, and mixture D is made, spare；Finally mixture D obtained is added in auxiliary material
It is uniformly mixed at room temperature, mixture E is made, it is spare；
Third walks, and mixture E obtained is directly sieved or grinding and sieving, sieve using 60~80 mesh sieve, by 50g~
1000g is sub-packed in packaging bag or Packaging Bottle, finished product after sealing or gland.
The beneficial effects of the invention are as follows：Trimethoprim sodium (TMP sodium) also known as methoxybenzyl aminopyrimidine sodium, trimethoxy benzyl ammonia are phonetic
Pyridine sodium dissolves in water for white or yellowish crystalline powder, mildly bitter flavor, and this product pharmacological action is broad spectrum antibiotic, antibacterial
Spectrum seemingly, plays the role of inhibiting dihyrofolate reductase, but bacterium is relatively also easy to produce drug resistance, seldom be used alone with sulfa drugs.
It is shared with sulfa drug, the folic acid metabolism of bacterium can be made by double blocking, thus antibacterial action increases substantially, it can antibacterial action
Enhance several times to tens times, therefore have the title of trimethoprim (TMP), and the appearance of drug resistance strain can be reduced.TMP sodium is as antibacterial synergy
Medicine, (generally in 1: 5 or 1: 3 ratio use) is mainly shared with sulfa drug can make sulfa drug antibacterial, antiprotozoan effect enhancing number
Again to decades of times, it is secondary thin that septicemia, white diarrhea, avian typhoid, cholera, respiratory system caused by poultry Escherichia coli can be treated
Bacterium infection etc..It can be additionally used in the prevention of globidiosis.This product oral absorption is complete, wide after absorption up to 90% or more of dosage
It is distributed in the tissue and body fluid of whole body generally, may pass through blood-brain barrier, cerebrospinal fluid drug concentration is up to blood in meninx inflammation
The 50%~100% of liquid concentration may pass through placenta and enter in fetus body, and fetal circulation blood concentration is close with parent blood concentration,
The product are mainly through renal excretion, and discharge rate is the 40%~60% of dosage in urinating for 24 hours：Wherein 80%~90% is arranged with drug original shape
Go out, product t1/2 is 8~10h.
Feature 1：The present invention selects TMP sodium to make synergist, and the advantage compared with TMP is, soluble easily in water, more suitable for the mixed drink of pulvis
Administration, this product is alkalinity, more suitable for the synergist as sulfa drug.
Nitazoxanide (nitazoxanide, NTZ) is a kind of nitrothiazole amino benzenes compounds, has broad-spectrum disease resistance substance
Activity, effectively to parasite, protozoon, bacterium and virus.Specifically include the protozoon, worm, anaerobic bacteria of intraor extracellular, and disease
Poison.Activity in vivo is related with its deacetylation derivative tizoxanide (tizoxanide, T).
Feature 2：The characteristics of above a few class drug combinations is that Nitazoxanide can enhance the antiprotozoan effect of sulfa drug, can be more
The sulfa drug disadvantage invalid to anaerobic bacteria when tip-in worm mixing anaerobic bacterium infects has prevention and treatment pig fowl protozoan infection and original
The good action of worm and bacteria mixed infection, diarrhea etc. as caused by pig fowl coccidia.The soluble powder of the present invention, to sulfanilamide (SN) medication
It is effective to imitate poor or invalid drug resistance coccidium infection.The shortcomings that Nitazoxanide is to be insoluble in water, is soluble in alkali, present invention addition
Stabilizer is added to improve its stability to improve its water solubility in cosolvent appropriate.The soluble powder of the present invention, passes through drink
Water is administered, easy to use, for preventing and treating the protozoan infection of pig fowl and protozoon and bacteria mixed infection, there is good result.
Specific implementation mode
With reference to embodiment, invention is further described in detail with specific implementation mode：
Embodiment 1
Nitazoxanide and sodium carbonate are mixed evenly in a manner of incremental step by step, obtain mixture A by the first step, then
Mixture A obtained is added in Sulfamonomethoxime Sodium and obtains mixture B, it is spare；
EDTA2 sodium and TMP sodium are mixed evenly to obtain mixture C, then mixture C obtained and mix by second step
It closes object B to be stirred at room temperature uniformly, mixture D is made, it is spare；Finally mixture D obtained is added in auxiliary material at room temperature
It is uniformly mixed, mixture E is made, it is spare；
Third walks, and mixture E obtained is directly sieved or grinding and sieving, and sieve is using 60~80 mesh sieve, by 100g
It is sub-packed in packaging bag, finished product after sealing.
Embodiment 2
Nitazoxanide and sodium benzoate are mixed evenly in a manner of incremental step by step, obtain mixture A by the first step,
Mixture A obtained is added in 5-methoxysulfadiazine sodium again and obtains mixture B, it is spare；
Sodium sulfite and TMP sodium are mixed evenly to obtain mixture C, then mixture C obtained and mix by second step
It closes object B to be stirred at room temperature uniformly, mixture D is made, it is spare；Finally mixture D obtained is added in auxiliary material at room temperature
It is uniformly mixed, mixture E is made, it is spare；
Third walks, and mixture E obtained is directly sieved or grinding and sieving, and sieve is using 60~80 mesh sieve, by 150g
It is sub-packed in Packaging Bottle, finished product after gland.
Embodiment 3
Nitazoxanide and sodium citrate are mixed evenly in a manner of incremental step by step, obtain mixture A by the first step,
Mixture A obtained is added in sulfaclozine sodium again and obtains mixture B, it is spare；
Mosatil and TMP sodium are mixed evenly to obtain mixture C by second step, then mixture C obtained with
Mixture B is stirred at room temperature uniformly, and mixture D is made, spare；Finally mixture D obtained is added in auxiliary material in room temperature
Under be uniformly mixed, be made mixture E, it is spare；
Third walks, and mixture E obtained is directly sieved or grinding and sieving, and sieve is using 60~80 mesh sieve, by 200g
It is sub-packed in packaging bag, finished product after sealing.
Claims (5)
1. boar fowl compound sulfonamide Nitazoxanide soluble powder, it is characterised in that：It is synthesized by the preparation of following component：Sulfa drug
20~30 grams, 4~10.0 grams of TMP sodium, 1.5~5 grams of Nitazoxanide, 5~25 grams of cosolvent, 1~7.5 gram, above group of stabilizer
Part is 100 grams with the mixed total amount of auxiliary material；
Preparation method, concrete operation step are as follows：
The Nitazoxanide and the cosolvent are mixed evenly in a manner of incremental step by step, obtain mixture by the first step
A, then mixture A obtained is added in the sulfa drug and obtains mixture B, it is spare；
The stabilizer and the TMP sodium are mixed evenly to obtain mixture C by second step, then mixture C obtained with
Mixture B is stirred at room temperature uniformly, and mixture D is made, spare；Finally mixture D obtained is added in auxiliary material in room temperature
Under be uniformly mixed, be made mixture E, it is spare；
Third walks, and mixture E obtained is directly sieved or grinding and sieving, sieve using 60~80 mesh sieve, by 50g~
1000g is sub-packed in packaging bag or Packaging Bottle, finished product after sealing or gland.
2. boar fowl according to claim 1 compound sulfonamide Nitazoxanide soluble powder, it is characterised in that：Described
Sulfa drug is Sulfamonomethoxime Sodium or 5-methoxysulfadiazine sodium or Embazin or sulfaclozine sodium,
One or more of combination.
3. boar fowl according to claim 1 compound sulfonamide Nitazoxanide soluble powder, it is characterised in that：Described
Cosolvent is sodium citrate or sodium carbonate or sodium benzoate or potassium carbonate or meglumine, one such or several group
It closes.
4. boar fowl according to claim 1 compound sulfonamide Nitazoxanide soluble powder, it is characterised in that：Described
Stabilizer is selected from EDTA2 sodium or mosatil or sodium tripolyphosphate or sodium sulfite, one such or several group
It closes.
5. boar fowl according to claim 1 compound sulfonamide Nitazoxanide soluble powder, it is characterised in that：Described
Auxiliary material be 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 such or several combination.
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201610353200.4A CN105998036B (en) | 2016-05-19 | 2016-05-19 | One boar fowl compound sulfonamide Nitazoxanide soluble powder |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201610353200.4A CN105998036B (en) | 2016-05-19 | 2016-05-19 | One boar fowl compound sulfonamide Nitazoxanide soluble powder |
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| Publication Number | Publication Date |
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| CN105998036A CN105998036A (en) | 2016-10-12 |
| CN105998036B true CN105998036B (en) | 2018-07-27 |
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Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
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| 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 |
Citations (3)
| 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 |
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2016
- 2016-05-19 CN CN201610353200.4A patent/CN105998036B/en active Active
Patent Citations (3)
| 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 |
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