CN102397552B - A kind of medicine compound preparation of quinolone containing class and its preparation method and application - Google Patents
A kind of medicine compound preparation of quinolone containing class and its preparation method and application Download PDFInfo
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Abstract
The invention discloses medicine compound preparation of a kind of quinolone containing class and its preparation method and application. The medicine compound preparation of quinolone containing class of the present invention includes following component by mass percentage: quinolones or its esters compound 0.5��95%, organic acid or its esters compound 1��97%, sweeting agent 1��98.5%, flavour enhancer 0��45%, flavouring agent 0��10%, surplus is excipient. The finished product that the medicine compound preparation of quinolone containing class of the present invention prepares is stable, favorable dispersibility, good palatability, it is prone to absorb, can as broad spectrum antimicrobicide, have that bactericidal activity is strong, distribution in vivo wide and other antibacterials are without the advantage of cross resistance, antibacterial, mycoplasma is all effective, can be used for animal because of the treatment of the various infectious disease of the digestive system caused by sensitive organism or mycoplasma, respiratory system, urinary system or skin soft tissue.
Description
Technical field
The present invention relates to field of pharmaceutical preparations, be specifically related to medicine compound preparation of a kind of quinolone containing class and its preparation method and application.
Background technology
Quinolones (4-quinolones), also known as pyridonecarboxylic acids or pyridone acids, is the synthetic antibacterial drug that a class is newer, usually with the DNA of antibacterial for target, hindering DNA gyrase, further causing the irreversible lesion of DNA of bacteria, thus reaching antibacterial effect. Almost without cross resistance between such medicine, it it is desirable antimicrobial drug.
There is many deficiencies in traditional quinolones preparation and medication, as: use inconvenience, drug bioavailability is not high and the displeased acceptance of user etc., limit to the use scope of quinolone medicine greatly, all bring inconvenience to medication person and user. Application number be 92110768.4 Chinese patent disclose the preparation capable of permeating skin of a kind of quinolone containing class medicine, the adjuvants such as the salt that generates and dermal osmosis accelerator that reacted by quinolones and acid or alkaline matter are made, by percutaneous drug delivery, Transdermal absorption, it is possible to directly embrocate the patient or suffer from hide skin of applying ointment or plaster; Application number is that the Korean Patent of 20020089783 is by beta-cyclodextrin inclusion compound enrofloxacin, interpolation odor mask such as rice crust perfume, aspartame etc.; The Chinese patent that the patent No. is 200610049243.X carrys out taste masking by employing gelatin encapsulation technology, makes feed additive; The patent No. be 200510050039.5 Chinese patent protect a kind of 'Ennoxacin ' micro-capsule and preparation method, enrofloxacin is made microcapsule by use coating materials by it, and then reaches the purpose of taste masking; Application number be 200810091851.6 Chinese patent disclose a kind of palatability etc. being improved enrofloxacin by peplos microcapsule technology, but above-mentioned patent is only by external skin, owing to transdermal administration drug loading is little, and the epidermal area of domestic animal, skin corium and subcutaneous tissue are all thicker, as systemic applications, curative effect internal it is extremely difficult to effective blood drug concentration, so cannot be ensured;Or making an addition in feedstuff, meet water or running into saliva in animal oral cavity process or broken through chewing, the unpleasant taste of principal agent easily discharges, animal refusal is made to search for food.
WO2010034853 discloses and a kind of adopts xylitol and arginine as the quinolones solid of odor mask and liquid preparation, but xylitol make consumption will more than 20��70 times of up to principal agent time pig just can search for food, the principal agent concentration preparation more than 5% cannot be made, therefore substantially increase production cost in process of production and correspondingly too increase use cost, and the substantial amounts of xylitol of animal edible may result in abdominal discomfort, rise gas, the even adverse effect such as laxativeness; The situation additionally, the pig only disclosing below 40kg in this patent application searches for food. It is known that bitterness can cause the aversive response of animal, it is believed that be a kind of defense mechanism resisting noxious substance, it plays vital effect (HernessMS in the long-term evolution process of animal, GilbertsonTA.AnnuRevPhysiol, 1999,61:873-900). Farrowing sow, nursing sow and breeding boar are because of its biological instinct, produce offspring bitter substance is particularly sensitive for guarantee, the big pig in fattening later stage is ripe due to every allelotaxis, its olfactory sensation and the sense of taste also pig than below 40kg is more sensitive, therefore the pig acceptable taste of below 40kg, farrowing sow, nursing sow, breeding boar and the big pig in fattening later stage may not accept.
The administering mode of current quinolones can be injection or mixed feeding administration, but both medications all exist some defects. If drug administration by injection principal agent is for Affected individuals, if colony is administered, labor intensity is big, and the stress of animal is also big. Main disadvantage is that of mixed feeding administration, the feed intake after animals got sick declines, and have impact on the intake of medicine, thus also have impact on the action effect of medicine.
The advantage of drinking water administration is in that to be suitable for colony's administration, will not produce stress, not by feed intake quantitative limitation, it is ensured that the absorption dosage of medicine, convenient and swift.
Summary of the invention
It is an object of the invention to the unhappiness according to existing quinolones is brought to animal due to the abnormal smells from the patient of medicine itself or taste when medication feel, the problem causing animal refusing to eat, there is provided one can make the positive common medicine of animal, the medicine compound preparation of the quinolone containing class of refusing to eat will not be produced because of the abnormal smells from the patient of medicine or taste.
Another object of the present invention is in that the preparation method providing the medicine compound preparation of above-mentioned quinolone containing class.
It is also an object of the present invention to provide the application of the medicine compound preparation of above-mentioned quinolone containing class.
Above-mentioned purpose of the present invention is achieved by the following technical programs:
A kind of medicine compound preparation of quinolone containing class, including following component by mass percentage: quinolones or its esters compound 0.5��95%, organic acid or its esters compound 0.1��97%, sweeting agent 0.1��98.5%, flavour enhancer 0��45%, flavouring agent 0��10%, surplus is excipient.
As a kind of preferred version, the medicine compound preparation of above-mentioned quinolone containing class includes following component by mass percentage: quinolones or its esters compound 1��50%, organic acid or its esters compound 1��65%, sweeting agent 1��50%, flavour enhancer 1��30%, flavouring agent 0.1��5%, surplus is excipient.
As one most preferably scheme, the medicine compound preparation of above-mentioned quinolone containing class includes following component by mass percentage: quinolones or its esters compound 2.5��30%, organic acid or its esters compound 5��35%, sweeting agent 3��35%, flavour enhancer 3��20%, flavouring agent 0.5��1%, surplus is excipient.
As a kind of preferred version, quinolones or its esters compound in the medicine compound preparation of described quinolone containing class are norfloxacin or its esters compound, enrofloxacin or its esters compound, ofloxacin or its esters compound, ciprofloxacin or its esters compound, pefloxacin or its esters compound, lomefloxacin or its esters compound, difloxacin or its esters compound, sarafloxacin or its esters compound, danofloxacin or its esters compound, Marbofloxacin or its esters compound, orbifloxacin or its esters compound; Described organic acid is citric acid, succinic acid, fumaric acid, malic acid, nicotinic acid, tartaric acid or salicylic acid; Sweeting agent is saccharin, alitame, neotame, sucralose, acesulfame potassium or P-ethoxyphellylurea; Described flavour enhancer is sodium glutamate or sodium chloride; Described flavouring agent is vanillin, ethyl vanillin, orange essence, cream flavour or chocolate essence; Described excipient is glucose, sucrose, lactose, dextrin, cyclodextrin or starch.
As one most preferably scheme, the quinolones in the medicine compound preparation of described quinolone containing class is ciprofloxacin or enrofloxacin, and described organic acid is succinic acid; Described organic acid salt compounds is sodium succinate; Described sweeting agent is alitame or sucralose.
A lot of animals are similar to people to the impression of carbohydrate, but the sweeting agent of non-carbohydrate there is is significant difference, a lot of mankind feel the material that sugariness is very high, some animals (such as pig) but do not feel (D.Glaseretal./FoodChemistry, 68 (2000) 375-385), such as that people's sugariness is significantly high aspartame, Talin, cyclamate, NHDC etc. all cannot by pig identification, this is because the taste receptors T1R1 of pig, T1R2, albumen on T1R3 is different, therefore these sweeting agents can not be used as the odor mask of quinolones.
Organic acid or its esters compound have strong tart flavour because of its mouthfeel, can reduce the animal sensation to bitterness and sweet taste to a certain extent; But the interference of bitterness identification is different by different organic acid, some is likely to result in more offending sensation, for instance cattle Dichlorodiphenyl Acetate and lactic acid all show detest and refusal (cross limit clear it, veterinary livestock products are newly reported). Succinic acid, it it is the raw material manufacturing chloramphenicol palmitate also known as succinic acid, carboxyl on succinic acid obtains synthomycetine succinate with the hydroxyl generation esterification on chloromycetin can make chloromycetin bitterness greatly reduce, but it is only physical mixed by succinic acid and chloromycetin, then cannot weaken or eliminate the bitterness of chloromycetin. Therefore the material that also not all mouthfeel is sour can act as odor mask and uses.
Suitable flavouring agent can lure feed intake, and some animals (such as pig) like fragrant, the chocolate perfume of milk, mandarin orange etc.
Suitable flavour enhancer is also a class material of Favourite of animal.
Containing when having plenty of quinolones in the compound formulation of quinolone containing class medicine of the present invention, its preparation method is that quinolones first becomes in organic solvent salt with organic acid, then mixs homogeneously with other each component again; Or each to quinolones and other component is mixed homogeneously; When in preparation containing when having plenty of the salt compounds of quinolones, its preparation method is the salt compounds of quinolones and other component to be mixed.
The compound formulation of quinolone containing class medicine of the present invention can as broad spectrum antibiotic, antibacterial, mycoplasma is all effective, can be used for animal because of the treatment of the various infectious disease of the digestive system caused by sensitive organism or mycoplasma, respiratory system, urinary system or skin soft tissue. This compound formulation can prepare into granule, powder, solution or effervescent by conventional method. The administering mode of animal is not limit, it is possible to be mixed feeding administration or drinking water administration.
Compared with prior art, there is advantages that
The compound formulation of quinolone containing class medicine of the present invention is by mixing the quinolones of specific amount ranges and sweeting agent, organic acid, flavour enhancer (optional), flavouring agent (optional), excipient, the compound formulation finished product prepared is stable, favorable dispersibility, good palatability, it is prone to absorb, no longer there are unhappy abnormal smells from the patient, the problem solving animal refusing to eat.The compound formulation of quinolone containing class medicine of the present invention can also be dissolved in water, allows animal take in medicine by the method for drinking water administration, it is to avoid animal causes that because sick appetite declines insufficient problem taken in by medicine.
Detailed description of the invention
The present invention is explained further below in conjunction with embodiment, but the present invention is not limited in any form by embodiment.
Embodiment 1
Enrofloxacin 359g is placed in the there-necked flask of 5L, adds in absolute methanol 1000ml, start stirring. Separately 118g succinic acid is dissolved in 600ml absolute methanol, is dropped in above-mentioned flask, be heated to reflux 4 hours, pick test, it is judged that after reaction end, stopped reaction, filtration, absolute methanol washing, drying, obtain 470g enrofloxacin succinate.
Embodiment 2
Levofloxacin 361g is placed in the there-necked flask of 5L, adds in dehydrated alcohol 1200ml, start stirring. Separately 192g citric acid is dissolved in 750ml dehydrated alcohol, is dropped in above-mentioned flask, be heated to reflux 5 hours, pick test, it is judged that after reaction end, stopped reaction, filtration, absolute ethanol washing, drying, obtain 543g levofloxacin citrate.
Embodiment 3
Enrofloxacin succinate embodiment 1 prepared is with other components are blended by following prescription, pulverize, sieve, and well-established law prepares enrofloxacin powder.
Enrofloxacin succinate 13.3%
Sucralose 5%
Ethyl vanillin 0.5%
Sodium chloride 30%
Anhydrous glucose adds to full dose 100%.
Embodiment 4
Enrofloxacin 0.5%
Succinic acid 95%
Sucralose 3%
Vanillin 0.1%
Sucrose adds to full dose 100%
Mix, pulverize, sieve, wet granulation, to dry, well-established law prepares granule.
Embodiment 5
Enrofloxacin 20%
Citric acid 15%
Alitame 3%
Ethyl vanillin 0.5
Sodium chloride 15%
Starch adds to full dose 100%
Mixing, pulverize, sieve, well-established law prepares powder.
Embodiment 6
By the enrofloxacin powder that embodiment 3 method prepares, with 5% alcoholic solution of PVP for binding agent, wet granulation, to dry, well-established law prepares granule.
Embodiment 7
Enrofloxacin 75%
Fumaric acid 12%
Alitame 10%
Dextrin adds to full dose 100%
Mixing, pulverize, sieve, well-established law prepares powder.
Embodiment 8
Enrofloxacin sodium 95%
Succinic acid sodium salt 1%
Sodium glutamate 3%
Neotame 0.1%
Lactose adds to full dose 100%
Mixing, pulverize, sieve, well-established law prepares powder, or well-established law makes granule.
Embodiment 9
Ciprofloxacin hydrochloride 35%
Malic acid 10%
Acesulfame potassium 50%
Soluble starch adds to full dose 100%
Mixing, pulverize, sieve, well-established law prepares powder.
Embodiment 10
The powder that embodiment 9 is prepared, with starch slurry for binding agent, wet granulation, dry, obtain granule.
Embodiment 11
Norfloxacin nicotinic 14%
Citric acid 24%g
Sodium bicarbonate 30%
P-ethoxyphellylurea 10%
Dextrin 10%
Lactose adds to full dose 100%
Said components is pulverized respectively, sieve, dry, control moisture below 1%, by norfloxacin nicotinic, P-ethoxyphellylurea, dextrin and lactose mix homogeneously; Adding aforementioned component mixing after sodium bicarbonate, citric acid being granulated respectively, with PVP ethanol solution for binding agent, well-established law is granulated, and obtains effervescent granule again.
Embodiment 12
By the prescription of embodiment 11 and preparation method, add appropriate PEG6000 as releasing agent, with PVP for binding agent, well-established law tabletting, prepare norfloxacin effervescent tablet.
Embodiment 13
Levofloxacin citrate 0.5%
Acesulfame potassium 98.5%
Glucose adds to full dose 100%
Mixing, pulverize, sieve, well-established law prepares powder.
Embodiment 14
Sarafloxacin hydrochlorate 11%
Salicylic acid 40%
Sucralose 20%
Cream flavour 0.5%
Sodium glutamate 12.5%
Lactose adds to full dose 100%
Mixing, pulverize, sieve, well-established law prepares powder.
Embodiment 15
Enrofloxacin 2.5%
Succinic acid 45%
Alitame 8%
EDTA0.05%
Sodium chloride 10%
Citrus flavor 1%
Purified water adds to full dose 100%w/vw
Enrofloxacin is placed in the 1/2 of full dose purified water, adds succinic acid stirring and dissolving, then all the other components are added stirring and dissolving, add residue purified water, constant volume, filter with 0.45 micron membranes, fill, sterilizing, obtained solution agent.
Embodiment 16
Difloxacin 20%
Tartaric acid 44%
Alitame 12%
Chocolate essence 0.5%
Sodium chloride 22%
Glucose adds to full dose 100%
Mixing, pulverize, sieve, well-established law prepares powder.
Embodiment 17
Enrofloxacin sodium 10.7%
Potassium citrate 12.5%
Saccharin 40%
Sodium glutamate 20%
Cream flavour 0.8%
Glucose adds to full dose 100%
Mixing, pulverize, sieve, well-established law prepares powder.
Embodiment 18
Danofloxacin mesylate 25.4%
Fumaric acid 8%
Sucralose 9.5%
Citrus flavor 1%
Lactose adds to full dose 100%
Mixing, pulverize, sieve, well-established law prepares powder.
Embodiment 19
Pefloxacin mesylate 12.9%
Salicylic acid 5%
Alitame 5%
Cream flavour 1%
Dextrin adds to full dose 100%
Mixing, pulverize, sieve, well-established law prepares powder.
Embodiment 20
Marbofloxacin 20%
Fumaric acid 10%
Succinic acid 8%
Alitame 15%
Vanillin 0.1%
Glucose adds to full dose 100%
Mixing, pulverize, sieve, conventional method prepares powder.
Embodiment 21
Lomefloxacin hydrochloride 35%
Salicylic acid 5%
Tartaric acid 10%
To oxygen ethyl phenylurea 20%
Chocolate essence 5%
Lactose adds to full dose 100%
Mix, pulverize, sieve, obtain powder.
Embodiment 22
Orbifloxacin 15%
Succinic acid 25%
Tartaric acid 10%
Sucralose 20%
Cream flavour 0.5%
Sucrose adds to full dose 100%
Mix, pulverize, sieve, obtain powder.
Embodiment 23
Healthy farrowing sow 96 (conceived 9 weeks), stochastic averagina is divided into 3 groups, administering mode: drinking water administration. If blank group: the clear water for being not added with any material of drinking water; Enrofloxacin HCL group: add Enrofloxacin HCL in drinking-water, be 0.1g/L (100ppm) by enrofloxacin concentration; The embodiment of the present invention 3 groups: add the powder that the embodiment of the present invention 3 prepares in drinking-water, be 0.1g/L (100ppm) by enrofloxacin concentration.
Preliminary experiment 3 days (being grouped but without medicine), records the amount of drinking water of 3 groups, essentially identical zero difference. Within 4th day, add, observe 12 hours, note down each group of amount of drinking water such as table 1 and show:
Table 1
Embodiment 24
Healthy farrowing sow 96 (conceived 11 weeks), stochastic averagina is divided into 3 groups, administering mode: drinking water administration. If blank group: the clear water for being not added with any material of drinking water; Enrofloxacin HCL group: add Enrofloxacin HCL in drinking-water, be 0.025g/L (25ppm) by enrofloxacin concentration; The embodiment of the present invention 15 groups: add the solution that the embodiment of the present invention 15 prepares in drinking-water, be 0.025g/L (25ppm) by enrofloxacin concentration.
Preliminary experiment 3 days (being grouped but without medicine), records the amount of drinking water of 3 groups, essentially identical zero difference. Within 4th day, add, observe 12 hours, note down each group of amount of drinking water such as table 2 and show:
Table 2
Embodiment 25
Healthy nursing sow 48 (2 weeks puerperal), stochastic averagina is divided into 3 groups, administering mode: drinking water administration.If blank group: the clear water for being not added with any material of drinking water; Enrofloxacin sodium group: add enrofloxacin sodium in drinking-water, be 0.1g/L (100ppm) by enrofloxacin concentration; The embodiment of the present invention 17 groups: add the powder that the embodiment of the present invention 17 prepares in drinking-water, be 0.1g/L (100ppm) by enrofloxacin concentration.
Preliminary experiment 3 days (being grouped but without medicine), records the amount of drinking water of 3 groups, essentially identical zero difference. Within 4th day, add, observe 12 hours, note down each group of amount of drinking water such as table 3 and show:
Table 3
Embodiment 26
Healthy Duroc breeding boar 48 (2 weeks puerperal), stochastic averagina is divided into 3 groups, administering mode: drinking water administration. If blank group: the clear water for being not added with any material of drinking water; Ciprofloxacin group: add ciprofloxacin in drinking-water, be 0.125g/L (125ppm) by ciprofloxacin concentration; The embodiment of the present invention 9 groups: add the powder that the embodiment of the present invention 9 prepares in drinking-water, be 0.125g/L (125ppm) by ciprofloxacin concentration.
Preliminary experiment 3 days (being grouped but without medicine), records the amount of drinking water of 3 groups, essentially identical zero difference. Within 4th day, add, observe 12 hours, note down each group of amount of drinking water such as table 4 and show:
Table 4
Embodiment 27
The pig 60 that bacterial diarrhea occurs of average weight 22kg, stochastic averagina is divided into 3 groups, administering mode: drinking water administration. If blank group: the clear water for being not added with any material of drinking water; Pefloxacin mesilate group: add pefloxacin mesilate in drinking-water, be 0.10g/L (100ppm) by pefloxacin concentration; The embodiment of the present invention 19 groups: add the powder that the embodiment of the present invention 19 prepares in drinking-water, be 0.10g/L (100ppm) by pefloxacin concentration.
Observe 24 hours, note down each group of amount of drinking water and therapeutic effect such as table 5 shows:
Table 5
Embodiment 28
Healthy big pig (average weight 85kg) 180, stochastic averagina is divided into 3 groups, administering mode: drinking water administration. If blank group: the clear water for being not added with any material of drinking water; Levofloxacin hydrochloride group: add levofloxacin hydrochloride in drinking-water, be 0.05g/L (50ppm) by levofloxacin concentration; The embodiment of the present invention 13 groups: add the powder that the embodiment of the present invention 13 prepares in drinking-water, be 0.05g/L (50ppm) by levofloxacin concentration.
Observe 24 hours, note down each group of amount of drinking water such as table 6 and show:
Table 6
Embodiment 29
Health pig (average weight 67kg) 120, stochastic averagina is divided into 3 groups, administering mode: mixed feeding is administered; If blank group: feedstuff is without any medicine; Enrofloxacin HCL group: add Enrofloxacin HCL in feedstuff, be 0.10g/L (100ppm) by enrofloxacin concentration; The embodiment of the present invention 5 groups: add the powder that the embodiment of the present invention 5 prepares in feedstuff, be 0.10g/L (100ppm) by enrofloxacin concentration.
Preliminary experiment 3 days (be grouped, but respectively organize all without any medicine), each group feed intake is normal, essentially identical; Within 4th day, begin in feedstuff and add 3 days continuously, note down each group of feed intake such as table 7 and show. Drug withdrawal afterwards, then observe 3 days, each group feed intake recovers normal and essentially identical.
Table 7
* note: this group feed intake refers to 24 hour datas. Consider the growth of pig, after 24 hours, namely recover the blank feedstuff of supply.
Embodiment 30
The pig 60 that bacterial diarrhea occurs of average weight 35kg, stochastic averagina is divided into 5 groups, administering mode: drinking water administration. If blank group: the clear water for being not added with any material of drinking water; Abbott 56619 sand star group: add Abbott 56619 in drinking-water, be 0.025g/L (25ppm) by difloxacin concentration;The embodiment of the present invention 16 groups: add the powder that the embodiment of the present invention 16 prepares in drinking-water, be 0.025g/L (25ppm) by difloxacin concentration; Enrofloxacin HCL group: add Enrofloxacin HCL in drinking-water, be 0.05g/L (50ppm) by enrofloxacin concentration; The embodiment of the present invention 4 groups: add the granule that the embodiment of the present invention 4 prepares in drinking-water, be that 0.05g/L (50ppm) observes 24 hours by enrofloxacin concentration, note down each group of amount of drinking water and therapeutic effect such as table 8 shows:
Table 8
Embodiment 31
Disease of breathing pig (clinical indication is non-expectorant dry cough for average weight 59kg, mycoplasma infection, breathe, dyspnea, fever) 60, stochastic averagina is divided into 3 groups, administering mode: mixed feeding is administered; If blank group: feedstuff is without any medicine; Enrofloxacin HCL group: add Enrofloxacin HCL in feedstuff, be 0.10g/L (100ppm) by enrofloxacin concentration; The embodiment of the present invention 5 groups: add the powder that the embodiment of the present invention 5 prepares in feedstuff, be 0.10g/L (100ppm) by enrofloxacin concentration.
Feedstuff adds 3 days continuously, notes down each group of feed intake and clinical symptoms is improved such as table 9 and shown. Drug withdrawal afterwards, then observe 3 days, each group feed intake recovers normal and essentially identical.
Table 9
* note: Enrofloxacin HCL matched group feed intake refers to 24 hour datas. Consider the healthy growth of pig, namely recover the blank feedstuff of supply after 24 hours, but do not count. Clinical symptoms is improved standard and is referred to that the mental status is normal without cough, fever, searches for food and drinks water normal.
Embodiment 32
Suffer from the milch cow 6 of acute mastitis, clinical symptoms: palpation breast has grade fever, pain, swelling. Milk has floccule or grumeleuse, and milk is thinning, pH value meta-alkalescence, and Somatic Cell Count and chloride content all increase, and stochastic averagina is divided into 2 groups, administering mode: drinking water administration. If matched group: intramuscular injection, take commercially available enrofloxacin injection, by per kilogram of body weight 2.5mg (in enrofloxacin) intramuscular injection, every day 1 time, be used in conjunction 5 days; The embodiment of the present invention 4 groups: add the granule that the embodiment of the present invention 4 prepares in drinking-water, be 0.025g/L (25ppm) by enrofloxacin concentration
Observe 5 days, note down each group of amount of drinking water and therapeutic effect such as table 10 shows:
Table 10
* note: clinical symptoms improvement rate is every clinical symptoms index to be added and calculate and obtain
Embodiment 33
The white meat-type chickens 90 of 35 age in days generation colibacillosiss, stochastic averagina is divided into 3 groups, administering mode: drinking water administration. If blank group: the clear water for being not added with any material of drinking water; Enrofloxacin sodium group: add enrofloxacin sodium in drinking-water, be 0.10g/L (100ppm) by enrofloxacin concentration; The embodiment of the present invention 17 groups: add the powder that the embodiment of the present invention 17 prepares in drinking-water, be 0.10g/L (100ppm) by enrofloxacin concentration; Continuous use 3 days, observes and notes down each group of amount of drinking water and therapeutic effect such as table 11 shows:
Table 11
Claims (4)
1. the medicine compound preparation of a quinolone containing class, it is characterized in that including following component by mass percentage: quinolones or its esters compound 2.5��30%, organic acid or its esters compound 5��35%, sweeting agent 3��35%, flavour enhancer 3��20%, flavouring agent 0.5��1%, surplus is excipient;
Described organic acid is citric acid, succinic acid or malic acid; Sweeting agent is saccharin, alitame, sucralose or acesulfame potassium;Described flavour enhancer is sodium glutamate or sodium chloride; Described flavouring agent is vanillin, ethyl vanillin, orange essence, cream flavour or chocolate essence; Described excipient is glucose, sucrose, lactose, dextrin, cyclodextrin or starch; Described compound formulation is applicable to pig, cattle; Described quinolones or its esters compound are norfloxacin, ciprofloxacin, pefloxacin, enrofloxacin, difloxacin, sarafloxacin, lomefloxacin, ofloxacin, Marbofloxacin, orbifloxacin or its esters compound.
2. the medicine compound preparation of quinolone containing class according to claim 1, it is characterised in that described quinolones is ciprofloxacin or enrofloxacin.
3. the medicine compound preparation of quinolone containing class according to claim 1, it is characterised in that described organic acid is succinic acid, described organic acid salt compounds is sodium succinate.
4. the preparation method of the compound formulation of quinolone containing class medicine described in claims 1 to 3, it is characterized in that when in preparation containing when having plenty of quinolones, described preparation method is that quinolones first becomes in organic solvent salt with organic acid, then mixs homogeneously with other each component again; Or each to quinolones and other component is mixed homogeneously; When in preparation containing when having plenty of the salt compounds of quinolones, described preparation method is by the salt compounds of quinolones and the mixing of other component.
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| CN103006660A (en) * | 2012-08-09 | 2013-04-03 | 江苏科技大学 | Sarafloxacin hydrochloride bactericide for silkworms and preparation method for capsules thereof |
| CN102860995A (en) * | 2012-08-31 | 2013-01-09 | 格特生物制药（天津）有限公司 | Enrofloxacin effervescent granule for livestock and preparation method thereof |
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| WO2020047198A1 (en) | 2018-08-31 | 2020-03-05 | Incyte Corporation | Salts of an lsd1 inhibitor and processes for preparing the same |
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Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1518449A (en) * | 2001-06-20 | 2004-08-04 | ����˹�ж�-����˹˹������˾ | Pediatric formulation of gatifloxacin |
| CN1642415A (en) * | 2002-03-12 | 2005-07-20 | 布里斯托尔-迈尔斯斯奎布公司 | Palatable oral suspension and method |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2005507397A (en) * | 2001-10-09 | 2005-03-17 | ブリストル−マイヤーズ スクイブ カンパニー | Fast-dissolving oral formulation |
| CN101190194A (en) * | 2006-11-29 | 2008-06-04 | 天津市润拓生物技术有限公司 | Enrofloxacin chewable tablets for dog or cat |
-
2010
- 2010-09-10 CN CN201010281456.1A patent/CN102397552B/en active Active
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| CN1518449A (en) * | 2001-06-20 | 2004-08-04 | ����˹�ж�-����˹˹������˾ | Pediatric formulation of gatifloxacin |
| CN1642415A (en) * | 2002-03-12 | 2005-07-20 | 布里斯托尔-迈尔斯斯奎布公司 | Palatable oral suspension and method |
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