CN103705444A - Veterinary oxytetracycline-in situ gel medicinal composition and preparation method thereof - Google Patents
Veterinary oxytetracycline-in situ gel medicinal composition and preparation method thereof Download PDFInfo
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- CN103705444A CN103705444A CN201310714355.2A CN201310714355A CN103705444A CN 103705444 A CN103705444 A CN 103705444A CN 201310714355 A CN201310714355 A CN 201310714355A CN 103705444 A CN103705444 A CN 103705444A
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Abstract
The invention discloses a novel preparation of an oxytetracycline-in situ gel medicinal composition. The medicinal composition can be applied or sprayed to the surface of nipples of a sow, and can quickly turn into an immobilized gel state, and the medicine can be absorbed by a piglet by suckling. The preparation can be used for preventing piglet diarrhea, enables the diarrhea resistance of the piglet to be reinforced, and has a treatment effect.
Description
Technical field
The present invention relates to infection veterinary drug, particularly a kind of oxytetracycline situ-gel pharmaceutical composition.
Background technology
Hyperpyrexia due to pig bacterial infects is a kind of commonly encountered diseases of pig, can cause that temperature of pig body raises, affects food ration and growth performance etc., can cause pig undergrowth and weightening finish, immune function to decline, and marketing period is extended.
The Main Pathogenic Bacteria of pig hyperpyrexia has pasteurellosis bacillus, streptococcus etc., and veterinary clinic infects the choice drug of the hyperpyrexia causing using oxytetracycline (Terramycinum) as pig bacterial.Oxytetracycline belongs to Tetracyclines broad-spectrum antibiotic, except Gram-positive and negative bacterium are had bacteriostasis, chlamydia, mycoplasma (as mycoplasma hyopneumoniae), various rickettsia, spirillum, actinomycetes and some protozoon also have inhibitory action to a certain degree.
To Adult Pig medication, can adopt 2.5% tetramycin hydrochloride 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 object of the invention is to infect for solving piglet bacillary the discomfort that the hyperpyrexia cause causes, and piglet dysentery is played to preventive and therapeutic action, a kind of oxytetracycline situ-gel for the treatment of both the principal and secondary aspects of a disease is provided.The oxytetracycline situ-gel preparing is sprayed directly on to 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 oxytetracycline simultaneously, easy to use, guarantees curative effect.
The invention discloses a kind of oxytetracycline situ-gel pharmaceutical composition.
Oxytetracycline situ-gel pharmaceutical composition in the present invention is comprised of pharmaceutical composition and the situ-gel material containing oxytetracycline.
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 oxytetracycline 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), (Poloxamer 188 for PLURONICS F87, 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 oxytetracycline situ-gel pharmaceutical composition and the demand of curative effect, containing in the pharmaceutical composition of oxytetracycline, can contain antioxidant.Antioxidant is selected from dibenzylatiooluene, 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, ascorbyl palmitate, glutathion, Hydros, lecithin, the tert-butyl group is to hydroxyl methoxybenzene, 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, ethylenediamine, dithioglycerol, 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 sodium sulfite, sodium thiosulfate, formaldehyde closes time sodium sulfite, sodium pyrosulfite, anhydrous sodium sulfite.
According to the character of oxytetracycline situ-gel pharmaceutical composition and the demand of curative effect, containing in the pharmaceutical composition of oxytetracycline, 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.
Accompanying drawing explanation
Fig. 1. oxytetracycline situ-gel pharmaceutical composition situ-gel is at room temperature mobile shape
Fig. 2. oxytetracycline situ-gel pharmaceutical composition situ-gel is gel state under 37 ℃ of conditions
Fig. 3. oxytetracycline situ-gel compositions extracorporeal bacteria inhibitor test
The specific embodiment
Embodiment 1. oxytetracycline temperature sensitivity situ-gel pharmaceutical composition preparations
The mycin that fetches earth adds water heating to be made 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 oxytetracycline, poloxamer188, PLURONICS F87, sodium sulfite and the disodium edetate in position concentration in gel are respectively 2.5% (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. oxytetracycline temperature/ion-sensitive situ-gel pharmaceutical composition preparations
The mycin that fetches earth adds water heating to be made 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 oxytetracycline, poloxamer188, PLURONICS F87, gellan gum, sodium sulfite and the disodium edetate in position concentration in gel are respectively 2.5% (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 oxytetracycline situ-gel pharmaceutical composition effect proof for animals.
Experimental example 1. oxytetracycline situ-gel pharmaceutical composition extracorporeal bacteria inhibitor tests
Test drug: according to the prepared oxytetracycline situ-gel pharmaceutical composition of experimental example 1.
Golden staphylococci liquid is cultivated: get 5ml culture medium to sterilizing test tubes, draw 10 μ L bacterium liquid and add in test tube, overnight incubation in 37 ℃, 200rpm shaking table.
Cultivate the preparation of Nutrient agar for gold glucose coccus: 4g Carnis Bovis seu Bubali cream adds water 1000ml, tepor is dissolved, and is made into meat extract; 10g peptone and 5g sodium chloride add in meat extract, adjust pH to 7.5, boil, and add 17.5g agar, heating for dissolving; 120 ℃ of autoclaving agar solutions, culture dish 20min.The agar solution of subpackage sterilizing in super-clean bench, after letting cool, sealing is inverted into 4 ℃ of Refrigerator stores.
Bacteriostatic test: get 0.1mL gold glucose coccus drop and be added in flat board, with the coating of aseptic triangle rod evenly, cover ware lid, dry 5min, aseptic nipper is affixed on the filter paper (diameter 1cm) containing oxytetracycline situ-gel pharmaceutical composition containing center, bacterio-agar surface, is inverted and is put in 37 ℃ of constant temperature CO
2incubator, cultivates 24h, takes out rear measurement inhibition zone size.Result shows oxytetracycline situ-gel pharmaceutical composition fungistatic effect obviously (Fig. 3, inhibition zone 2.2cm).
The therapeutic effect of experimental example 2. oxytetracycline situ-gel pharmaceutical compositions to ill piglet
Laboratory animal: choose at random 60 of ill piglets, body weight 15～30kg.
Test drug: according to the prepared oxytetracycline situ-gel pharmaceutical composition of embodiment 1; 2.5% Ursocycline injection (self-control).
Test method: 60 ill piglets are divided into three groups at random by body weight.First group is blank group, not drug treatment; With oxytetracycline situ-gel pharmaceutical composition prepared in the embodiment of the present invention 1, treat for second group; With Ursocycline injection, treat for the 3rd group.Oxytetracycline 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; Ursocycline injection usage is: 10mg/kg, 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 | Oxytetracycline situ-gel pharmaceutical composition group | Ursocycline injection group |
| A dead number | 20 | 2 | 3 |
| Invalid number | 20 | 6 | 5 |
| Effective number | 0 | 10 | 10 |
| Cure a number | 0 | 2 | 2 |
| Rate of body weight gain (%) | - | 56.8 | 60.3 |
The above results shows that the effect of oxytetracycline situ-gel pharmaceutical composition and Ursocycline injection group is suitable, but the use of oxytetracycline situ-gel pharmaceutical composition is more convenient, and piglet is more easily accepted, and has greatly reduced people's manipulation strength.
Claims (10)
1. an oxytetracycline situ-gel pharmaceutical composition.
2. oxytetracycline situ-gel pharmaceutical composition as claimed in claim 1, is comprised of pharmaceutical composition and situ-gel material containing oxytetracycline.
3. oxytetracycline 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. oxytetracycline situ-gel pharmaceutical composition as claimed in claim 2, situ-gel material is thermosensitive in situ gel material.
5. oxytetracycline situ-gel pharmaceutical composition as claimed in claim 4, thermosensitive in situ gel material is selected from poloxamer188, PLURONICS F87, methylcellulose, hypromellose, chitosan spread out dirt thing, 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. oxytetracycline situ-gel pharmaceutical composition as claimed in claim 1, contains antioxidant.
7. oxytetracycline situ-gel pharmaceutical composition as claimed in claim 1, contains metal chelating agent.
8. oxytetracycline situ-gel pharmaceutical composition as claimed in claim 1, adopts following steps to prepare:
The mycin that fetches earth adds water heating to be made 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 oxytetracycline, poloxamer188, PLURONICS F87, sodium sulfite and the disodium edetate in position concentration in gel are respectively 2.5% (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. oxytetracycline situ-gel pharmaceutical composition as claimed in claim 1, infects for solving piglet bacillary the discomfort that the hyperpyrexia that causes causes, and piglet dysentery is played to preventive and therapeutic action.
10. oxytetracycline situ-gel pharmaceutical composition as claimed in claim 1 is sprayed on or is applied to sow nipple before piglet sucks the breast.
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201310714355.2A CN103705444A (en) | 2013-12-23 | 2013-12-23 | Veterinary oxytetracycline-in situ gel medicinal composition and preparation method thereof |
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| CN201310714355.2A CN103705444A (en) | 2013-12-23 | 2013-12-23 | Veterinary oxytetracycline-in situ gel medicinal composition and preparation method thereof |
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106309357A (en) * | 2016-11-08 | 2017-01-11 | 河南益华动物药业有限公司 | Oxytetracycline hydrochloride gel implant for livestock and preparation method thereof |
| CN109568262A (en) * | 2019-01-04 | 2019-04-05 | 华南农业大学 | A kind of Doxycycline Temperature-sensitive in situ gel uterus perfusion and preparation method thereof for sow |
-
2013
- 2013-12-23 CN CN201310714355.2A patent/CN103705444A/en active Pending
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106309357A (en) * | 2016-11-08 | 2017-01-11 | 河南益华动物药业有限公司 | Oxytetracycline hydrochloride gel implant for livestock and preparation method thereof |
| CN109568262A (en) * | 2019-01-04 | 2019-04-05 | 华南农业大学 | A kind of Doxycycline Temperature-sensitive in situ gel uterus perfusion and preparation method thereof for sow |
| CN109568262B (en) * | 2019-01-04 | 2021-12-24 | 华南农业大学 | Doxycycline temperature-sensitive in-vivo gel uterus perfusate for sows and preparation method thereof |
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Application publication date: 20140409 |