CN103705443A - Tylosin in situ gel drug composition for livestock and preparation method thereof - Google Patents
Tylosin in situ gel drug composition for livestock and preparation method thereof Download PDFInfo
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- CN103705443A CN103705443A CN201310714332.1A CN201310714332A CN103705443A CN 103705443 A CN103705443 A CN 103705443A CN 201310714332 A CN201310714332 A CN 201310714332A CN 103705443 A CN103705443 A CN 103705443A
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Abstract
The invention provides a tylosin in situ gel drug composition which is used for solving the problem that animals, especially piglets, are infected with mycoplasmata, treponematosis, staphylococcus, streptococcus, pasteurella and haemophilus influenzae. Before the piglets suck, the tylosin in situ gel drug composition is directly sprayed or smeared on nipples of sows and can quickly become gel with relatively high viscosity so as to be retained locally, so that the piglets take in tylosin while sucking. The tylosin in situ gel drug composition is convenient to use and ensures the curative effect.
Description
Technical field
The present invention relates to infection veterinary drug, particularly a kind of tylosin situ-gel pharmaceutical composition.
Background technology
Mycoplasmal pneumonia is a kind of chronic pneumonia being caused by mycoplasma hyopneumoniae, claims again epidemic swine pneumonia.Primary disease China local pig breed is obviously compared with introduced variety susceptible, and the pig that carries disease germs is the main source of infection of primary disease.Pathogen through aerosol or with sick porcine respiratory secretions direct contact infection.Pathogen is passed to piglet through sow there is lastingly primary disease in swinery, and its order of severity is often because density and the change of other environmental factors of management level, season, ventilation condition, pig have very big-difference.May betide the piglet in 2～3 week age the earliest, but general propagation being slowly more general in infection in 6～10 weeks age, until just there is manifest symptom during 3～6 monthly age in many pigs.
Tylosin belongs to macrolide antibiotics, and antimicrobial spectrum and erythromycin are similar, is a kind of Macrolide animal specific antibiotic being obtained by actinomyces streptomyces fradiae fermented extracted, has tylosin alkali, phosphate and 3 kinds of forms of tartrate.Tylosin phosphonate, as feed additive, is widely used in the feedstuff of pig, can shorten breeding cycle, improves the price of deed, effectively prevents and treats respiratory tract and digestive tract infection.Tylosin mainly exists with the form of the happy alkali of Thailand in vivo, can be combined with the ribosome of core biology in vivo, and amino acid incorporation peptide chain is synthetic, thereby suppresses the synthetic of infectious bacteria protein.Tylosin has a broad antifungal spectrum, all has excellent activity to microorganisms such as most of gram positive bacteria, part gram negative bacteria, vibrio, spirillum, coccidiosiss, especially mycoplasma infection is had to specially good effect, is the choice drug of anti-mycoplasma.Tylosin is mainly used in the infection that mycoplasma, treponematosis, staphylococcus, streptococcus, pasteurellosis bacillus, hemophilus influenza cause.Tylosin cures mainly the mycoplasma such as mycoplasma pneumoniae of swine, swine dysentery, Proliferative Enteritis and bacterial enteritis; The chronic respiratory tract disease that avian mycoplasmas causes, mycoplasma abscess, septicemia, synovitis; The pneumonia that Mycoplasma bovis causes and mastitis, metritis.There is good growth promoting function.Continuously low dosage is taken tylosin, can not only prevent disease, and can significantly promote growth of animal
To Adult Pig medication, can adopt 20% tylosin injection intramuscular injection or be ground into powder and mix in pig feed, give pig feeding.But more difficult to piglet medication, drug administration by injection complex operation, time-consuming length, efficiency are low, and it is poor to mix medicine feedstuff mouthfeel, and piglet is reluctant to eat, weak effect.
Situ-gel (In Situ Gel) refers at agents area, occur to change mutually after solution state administration, the non-chemically crosslinked semi-solid preparation forming, conventionally be divided into responsive to temperature type, pH responsive type, three kinds of Transformation Mechanism of ion-sensitive type, three's gelling of having complemented each other.Situ-gel has the highly hydrophilic three dimensional network structure of gel preparation and good histocompatibility.Said preparation is with solution morphology administration, because temperature, ionic strength or pH change, can in the short time, make solution become gel or the gellike state that viscosity is larger, in the local holdup time, extend, can increase drug absorption, reduce drug wastage, reduce the trouble in use procedure, and guaranteed curative effect of medication.
Summary of the invention
The invention discloses a kind of tylosin situ-gel pharmaceutical composition.
The object of the invention is for solving the animal infection that particularly piglet mycoplasma, treponematosis, staphylococcus, streptococcus, pasteurellosis bacillus, hemophilus influenza cause.The tylosin situ-gel pharmaceutical composition preparing is sprayed on or is applied to sow nipple before piglet sucks the breast, can become rapidly the gel state that viscosity is larger, in part, be detained, piglet sucks the breast and takes in tylosin simultaneously, easy to use, guarantees curative effect.
Tylosin situ-gel pharmaceutical composition in the present invention is comprised of pharmaceutical composition and the situ-gel material containing tylosin.
Situ-gel material in the present invention is selected from thermosensitive in situ gel material, pH sensitive in situ gels research material, ionic strength sensitive in situ gels research material, preferably from thermosensitive in situ gel material.Can be alone in these situ-gel materials tylosin situ-gel compositions in the present invention, also can share.
Thermosensitive in situ gel material refer on a certain temperature or under time, be easy fluent solution or dispersion liquid, when material temperature reach under this temperature or on after, be difficult mobile gel state.PH sensitive in situ gels research material refer on a certain pH (or acidity) value or under time, be easy fluent solution or dispersion liquid, when material pH reach under this pH value or on after, be difficult mobile gel state.It is relevant with environment intermediate ion intensity that ionic strength sensitive in situ gels research material refers to the character of material, and the variation of ionic strength directly affects the viscosity of material in solution, forms the degree of gel.Ion is generally Na
+, K
+, Ca
2+, Zn
2+.
Thermosensitive in situ gel material in the present invention is selected from poloxamer188 (Poloxamer407, P407), PLURONICS F87 (Poloxamer188, P188), methylcellulose, hypromellose, chitosan derivatives, polylactic acid-polyethylene glycol block copolymer, polylactic-co-glycolic acid-polyethyleneglycol block copolymer, second hydroxy ethyl cellulose, polycaprolactone polyethyleneglycol block copolymer, poly-N-isopropyl acrylamide, preferably from poloxamer188, PLURONICS F87, methylcellulose, polylactic acid-polyethylene glycol block copolymer, polylactic-co-glycolic acid-polyethyleneglycol block copolymer, polycaprolactone-polyethylene glycol block copolymer, poly-N-isopropyl acrylamide, more preferably from poloxamer188, PLURONICS F87, methylcellulose.
PH sensitive in situ gels research material in the present invention is selected from CAP (CAP), HP-55 (HPMCP), carbomer, chitosan, preferably from CAP, carbomer.Ionic strength sensitive in situ gels research material in the present invention is selected from alginate, gellan gum.
According to the character of tylosin situ-gel pharmaceutical composition and the demand of curative effect, containing in the pharmaceutical composition of tylosin, can contain antioxidant.Antioxidant is selected from hydroquinone, propyl gallate, ascorbyl palmitate, nor-pair of hydrogen guaiaretic acid, BHA, toluene di-tert-butyl phenol, pyrogallic acid and ester thereof, dithioglycollic acid, d-xylose, xylitol, fumaric acid, sodium formaldehyde sulphoxylate, glycine, alpha-tocopherol, α-tocopheryl acetate, gentisic acid ethanolamine, l-cysteine hydrochloride, d-cysteine, dl-cysteine, l-cysteine, d, l-cysteine hydrochloride, arabo-ascorbic acid, sodium erythorbate, hypophosphorous acid, sodium hypophosphite, potassium hypophosphite, methylene blue, sodium sulfite, sodium sulfite, inositol, gallic acid, nor-pair of hydrogen guaiaretic acid, progallin A, dodecyl gallate, propyl gallate, gallateoctylester, isoamyl gallate, ascorbic acid, sodium ascorbate, glutathion, Hydros, lecithin, malic acid, pentaerythritol phthalate, Gardenia Yellow, hydroquinone, citric acid, potassium citrate, sodium citrate, citric acid fatty glyceride, benadon, Pyridoxamine hydrochloride, l (+) tartaric acid, d-tartaric acid, dl-tartaric acid, d-potassium hydrogen tartrate, sodium potassium tartrate tetrahydrate, oxine, oxine sodium, Polymeric sodium metaphosphate., potassium metaphosphate, methionine, thioglycerol, THIOGLYCOL, dithioglycerol, ethylenediamine, two sulfur ethylenediamines, sulfo-sorbitol, thioglucose, sodium thiosulfate, thiourea, allylthiourea, 6-methyl-2-deracil, sulfuric acid oxidation quinoline, hydroxyacetic acid, hydroxy acid sodium, 3-mercaptopropionic acid, alpha-mercapto propanoic acid, dimercaptosuccinic acid, alpha-mercapto N-Propionylglycine, o-mercaptobenzoic acid, 3,3 '-thio-2 acid, succinic acid, sodium succinate, glucono-δ-lactone, sodium pyrosulfite, potassium metabisulfite, phytic acid, sodium polyacrylate, polyacrylic acid, polyvinyl acetate, polyvinyl acetate phthalate, PHOSPHATIDYL ETHANOLAMINE, two Semen Myristicae PHOSPHATIDYL ETHANOLAMINE, two Petiolus Trachycarpi PHOSPHATIDYL ETHANOLAMINE, distearyl phosphatidyl ethanolamine, preferably from BHA, toluene di-tert-butyl phenol, sodium sulfite, sodium thiosulfate, formaldehyde closes time sodium sulfite, sodium pyrosulfite, anhydrous sodium sulfite.
According to the character of tylosin situ-gel pharmaceutical composition and the demand of curative effect, containing in the pharmaceutical composition of tylosin, can contain metal chelating agent.Metal chelating agent is selected from disodium edetate, calcium disodium edetate, diethyl triamine five acetic acid, dimercaptopropanol, BAL, preferably from disodium edetate, calcium disodium edetate.
The preparation method of situ-gel pharmaceutical composition can be with reference to pertinent literature and professional technique.Usually, situ-gel substrate is placed in to suitable quantity of water or aqueous solution, fully swelling.In the matrix solution of swelling, add pharmaceutical composition, fully disperse or dissolve.Add antioxidant subpackage.The particularity of this original position gel medicine composition is to be used in conjunction with the environmental sensitivity situ-gel material of different mechanisms, makes its fast gelation.
The specific embodiment
Embodiment 1. tylosin temperature sensitivity situ-gel pharmaceutical composition preparations
Getting tylosin phosphonate adds water and makes molten, add poloxamer188 and PLURONICS F87, adding water to 50mL makes it fully be swelled into homogeneous solution, add sodium sulfite and disodium edetate, stirring and dissolving, final tylosin phosphonate, poloxamer188, PLURONICS F87, sodium sulfite and the disodium edetate in position concentration in gel are respectively 20% (W/V), 15% (W/V), 15% (W/V), 2% (W/V), 0.5% (W/V), are distributed into container or sprayer unit is standby.
Embodiment 2. tylosin temperature/ion-sensitive situ-gel pharmaceutical composition preparations
Getting tylosin phosphonate adds water and makes molten, add poloxamer188, PLURONICS F87, gellan gum, adding water to 50mL makes it fully be swelled into homogeneous solution, add sodium sulfite and disodium edetate, stirring and dissolving, final tylosin phosphonate, poloxamer188, PLURONICS F87, gellan gum, sodium sulfite and the disodium edetate in position concentration in gel are respectively 20% (W/V), 15% (W/V), 15% (W/V), 0.7% (W/V), 2% (W/V), 0.5% (W/V), are distributed into container or sprayer unit is standby.
It is below the experimental example about tylosin situ-gel pharmaceutical composition effect proof for animals.
Experimental example. the therapeutic effect of tylosin situ-gel pharmaceutical composition to ill piglet
Laboratory animal: choose at random 60 of ill piglets, body weight 15～30kg.
Test drug: according to the prepared tylosin situ-gel pharmaceutical composition of embodiment 1; 20% tylosin injection (preparation of this laboratory).
Test method: 60 ill piglets are divided into three groups at random by body weight.First group is blank group, not drug treatment; With tylosin situ-gel pharmaceutical composition prepared in the embodiment of the present invention 1, treat for second group; With tylosin injection, treat for the 3rd group.Tylosin situ-gel usage is: one day 3 times, and before each piglet sucks the breast, be applied to or be sprayed on each nipple of sow, be used in conjunction 3 days; Tylosin injection usage is: 0.5ml/ piglet, 2 times on the one, is used in conjunction 3 days.
After treatment starts, every day entry suffers from poultry health situation of change and dead animal distributes, and treats and adds up therapeutic effect after 10 days.
Treatment standard:
Invalid: to refer to after 10 days, suffer from poultry symptom without obvious change, still keep treating front symptom (comprising a dead number).
Effective: refer to after 10 days, suffer from poultry symptom and change, symptom is better than treating front effect.
Cure: refer to after 10 days that transference cure is suffered from poultry and got well.
Rate of body weight gain: refer to respectively organize afterwards for 10 days and respectively organize average weight before average weight starts with treatment and compare gain percentage.
Following table is therapeutic effect statistics.
| ? | Matched group | Tylosin situ-gel pharmaceutical composition group | Tylosin injection group |
| A dead number | 20 | 2 | 2 |
| Invalid number | 20 | 5 | 5 |
| Effective number | 0 | 10 | 10 |
| Cure a number | 0 | 3 | 3 |
| Rate of body weight gain (%) | - | 55.8 | 57.3 |
The above results shows that the effect of tylosin situ-gel pharmaceutical composition and tylosin injection group is suitable, but the use of tylosin situ-gel pharmaceutical composition is more convenient, and piglet is more easily accepted, and has greatly reduced people's manipulation strength.
Claims (10)
1. a tylosin situ-gel pharmaceutical composition.
2. tylosin situ-gel pharmaceutical composition as claimed in claim 1, is comprised of pharmaceutical composition and situ-gel material containing tylosin.
3. tylosin situ-gel pharmaceutical composition as claimed in claim 2, situ-gel material is selected from thermosensitive in situ gel material, pH sensitive in situ gels research material, ionic strength sensitive in situ gels research material.
4. tylosin situ-gel pharmaceutical composition as claimed in claim 2, situ-gel material is thermosensitive in situ gel material.
5. tylosin situ-gel pharmaceutical composition as claimed in claim 4, thermosensitive in situ gel material is selected from poloxamer188, PLURONICS F87, methylcellulose, hypromellose, chitosan derivatives, polylactic acid-polyethylene glycol block copolymer, polylactic-co-glycolic acid-polyethyleneglycol block copolymer, second hydroxy ethyl cellulose, polycaprolactone polyethyleneglycol block copolymer, poly-N-isopropyl acrylamide.
6. tylosin situ-gel pharmaceutical composition as claimed in claim 1, contains antioxidant.
7. tylosin situ-gel pharmaceutical composition as claimed in claim 1, contains metal chelating agent.
8. tylosin situ-gel pharmaceutical composition as claimed in claim 1, adopts following steps to prepare:
Getting tylosin phosphonate adds water and makes molten, add poloxamer188 and PLURONICS F87, adding water to 50mL makes it fully be swelled into homogeneous solution, add sodium sulfite and disodium edetate, stirring and dissolving, final tylosin phosphonate, poloxamer188, PLURONICS F87, sodium sulfite and the disodium edetate in position concentration in gel are respectively 20% (W/V), 15% (W/V), 15% (W/V), 2% (W/V), 0.5% (W/V), are distributed into container or sprayer unit is standby.
9. tylosin situ-gel pharmaceutical composition as claimed in claim 1, for solving the animal infection that particularly piglet mycoplasma, treponematosis, staphylococcus, streptococcus, pasteurellosis bacillus, hemophilus influenza cause.
10. tylosin situ-gel pharmaceutical composition as claimed in claim 1 is sprayed on or is applied to sow nipple before piglet sucks the breast.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201310714332.1A CN103705443A (en) | 2013-12-23 | 2013-12-23 | Tylosin in situ gel drug composition for livestock and preparation method thereof |
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|---|---|---|---|
| CN201310714332.1A CN103705443A (en) | 2013-12-23 | 2013-12-23 | Tylosin in situ gel drug composition for livestock and preparation method thereof |
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| CN103705443A true CN103705443A (en) | 2014-04-09 |
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105943492A (en) * | 2016-06-14 | 2016-09-21 | 山东鲁抗舍里乐药业有限公司 | Tilmicosin in-situ-gel sustained-release injection and preparing method thereof |
| CN106420600A (en) * | 2016-09-21 | 2017-02-22 | 中国水产科学研究院珠江水产研究所 | In situ gel for tilmicosin injection and preparation method thereof |
| CN110693814A (en) * | 2019-10-09 | 2020-01-17 | 华中农业大学 | Veterinary tilmicosin nano-gel breast perfusion agent and preparation method thereof |
-
2013
- 2013-12-23 CN CN201310714332.1A patent/CN103705443A/en active Pending
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105943492A (en) * | 2016-06-14 | 2016-09-21 | 山东鲁抗舍里乐药业有限公司 | Tilmicosin in-situ-gel sustained-release injection and preparing method thereof |
| CN106420600A (en) * | 2016-09-21 | 2017-02-22 | 中国水产科学研究院珠江水产研究所 | In situ gel for tilmicosin injection and preparation method thereof |
| CN110693814A (en) * | 2019-10-09 | 2020-01-17 | 华中农业大学 | Veterinary tilmicosin nano-gel breast perfusion agent and preparation method thereof |
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Application publication date: 20140409 |