CN107334732A - A kind of rifaximin uterus injectant and preparation method and application - Google Patents
A kind of rifaximin uterus injectant and preparation method and application Download PDFInfo
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- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/439—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom the ring forming part of a bridged ring system, e.g. quinuclidine
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
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- A61K47/44—Oils, fats or waxes according to two or more groups of A61K47/02-A61K47/42; Natural or modified natural oils, fats or waxes, e.g. castor oil, polyethoxylated castor oil, montan wax, lignite, shellac, rosin, beeswax or lanolin
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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
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0034—Urogenital system, e.g. vagina, uterus, cervix, penis, scrotum, urethra, bladder; Personal lubricants
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Abstract
The invention discloses a kind of rifaximin uterus injectant and preparation method and application.The rifaximin uterus injectant is made up of following supplementary materials：0.05~0.5g of rifaximin, 0.125~1.25g of glycerin monostearate, 0.125~1.25g of suspending agent, vegetable oil add to 25g.The preparation method of the rifaximin uterus injectant comprises the following steps：1) after mixing the vegetable oil of partial amount and the glycerin monostearate, heating fusing, mixed system is obtained；2) vegetable oil of the suspending agent, the rifaximin and surplus is added into the mixed system, grinding is uniform, produces the rifaximin uterus injectant.The simple production process of rifaximin uterus injectant of the present invention, obtained preparation is uniformly, dispersed, stability is good, is easily enlarged metaplasia production；For invention formulation for parenteral solution, insoluble drug release is slow, and bioavilability is high, and low to tissue irritation, clinical efficacy is notable, has high promotional value.
Description
Technical field
The present invention relates to a kind of rifaximin uterus injectant and preparation method and application.
Background technology
Inflammation inflammation in cow uteri mainly has hysteritis, clinical type endometritis, Subclinical endometritis, son
Palace stores several clinical symptoms types such as purulence, is China milk cow postpartum common genital system diseases, can not only influence milk cow
Heat and gestation, reduce milk production of cow, induce the diseases such as milk room inflammation, the forfeiture of cow reproduction ability can be also caused when serious,
Some acute infected cattles can also cause septicemia and cause death, the serious sound development for hindering China's milk cow production, make simultaneously
Into huge economic loss.Such disease is mainly caused, the master that document report is clinically separated by microorganism infection in postpartum uterus
Pathogen is wanted to include：Escherichia coli, MRSE, staphylococcus aureus, bacillus cereus, non-hemolytic hammer
Bacterium, hemolytic streptococcus, campylobacter fetus, Pseudomonas aeruginosa and acinetobacter calcoaceticus etc..
Cow uteri inflammation is influenceed very big on milk cow production performance in clinical onset rate 35% or so.At present, uterus class is scorching
In the preventing and treating of disease, two large problems be present and be badly in need of solving：(1) food-safety problem of milk is considered, to select low-residual as far as possible
Time milk phase is abandoned in drug therapy, reduction；It is (2) clinically more to merge the mixed infections such as Gram-negative bacteria into gram-positive bacteria,
It is simple not notable using the effect of cephalosporins medicine；Therefore, be badly in need of wide spectrum, efficiently, safety, low-residual be used for cow uteri class
The uterus injectant class product of inflammation preventing and treating.
Rifaximin (Rifaximin) belongs to rifamycin analog derivative, is the first semi-synthetic antimicrobial of non-amino glycoside.
The characteristics of rifaximin is that has a broad antifungal spectrum, antibacterial activity are strong, and higher blood concentration is easily formed in enteron aisle.It is aerobic to Grain-positive
Golden yellow Portugal bacterium in bacterium, MRSE, enterococcus, clostridium difficile have height antibacterial activity；To Grain-negative large intestine bar
Bacterium, salmonella, Shigella, Yersinia and Grain-positive anaerobic bacteria also have good antibacterial activity.Rifaximin resists
Bacterium is composed and antibacterial activity is similar to rifampin, and the effect of its anti-gram positive bacteria is better than neomycin.
Rifaximin has the unique advantage being locally administered：With it is oral be not easy to absorb, safe efficient, low-residual, without stopping
The advantages that medicine phase.The medicine is developed by Italian Alpha Wei Shi Man (Alfa Wassermann), is to be used for first
People cures clinical prevention enteric infection as caused by gut flora and suffers from diarrhoea and treat the anti-infectious agent of intestines and stomach Postoperative infection,
Big profit that 1987 and 1998 fraction of the year, never mind and Mexico's listing, trade nameListed in Spain within 2003, commodity
It is entitledRatify to list a company in U.S. Salix through FDA within 2004, trade nameDue to rifaximin medicine
The characteristics of thing orally is not easy to absorb, in recent years its in the preventing and treating of veterinary clinic disease (particularly cow disease) increasingly by
Concern.Exploitation rifaximin local administration preparation has obviously advantage, while can also to treatment milk cow clinical disease
The generation of drug resistance, to reach prevention and treatment Animal diseases, reduces the mesh of the economic loss of aquaculture after effective prophylactic
, there is boundless application prospect.
The content of the invention
It is an object of the invention to provide a kind of rifaximin uterus injectant and preparation method thereof, profit provided by the present invention
Good fortune former times bright uterus injectant has significant curative effect to cow uteri inflammation (including hysteritis, endometritis, uterus suppuration etc.).
Rifaximin uterus injectant provided by the present invention, it is made up of following supplementary materials：Rifaximin (bulk drug)
0.05~0.5g, 0.125~1.25g of glycerin monostearate, 0.125~1.25g of suspending agent, vegetable oil add to 25g.
Further, the rifaximin uterus injectant is made up of following supplementary materials：0.1~0.5g of rifaximin, list
0.125~1.25g of tristerin, 0.125~1.25g of suspending agent, vegetable oil add to 25g.
Any of further, the rifaximin uterus injectant is following 1) -9)：
1) it is made up of following supplementary materials：
0.1~0.2g of rifaximin, 0.75~1.25g of glycerin monostearate, 0.125~0.75g of suspending agent, vegetable oil
Add to 25g；
2) it is made up of following supplementary materials：
0.1~0.2g of rifaximin, 0.125~0.75g of glycerin monostearate, 0.75~1.25g of suspending agent, vegetable oil
Add to 25g；
3) it is made up of following supplementary materials：
0.1~0.1875g of rifaximin, 0.25~0.75g of glycerin monostearate, 0.25~0.75g of suspending agent, plant
Oil adds to 25g；
4) it is made up of following supplementary materials：
0.1~0.5g of rifaximin, 0.25~0.75g of glycerin monostearate, 0.25~0.75g of suspending agent, vegetable oil
Add to 25g；
5) it is made up of following supplementary materials：
Rifaximin 0.1g, glycerin monostearate 0.75g, suspending agent 0.75g, vegetable oil add to 25g；
6) it is made up of following supplementary materials：
Rifaximin 0.1875g, glycerin monostearate 0.25g, suspending agent 0.25g, vegetable oil add to 25g；
7) it is made up of following supplementary materials：
Rifaximin 0.2g, glycerin monostearate 1.25g, suspending agent 0.125g, vegetable oil add to 25g；
8) it is made up of following supplementary materials：
Rifaximin 0.2g, glycerin monostearate 0.125g, suspending agent 1.25g, vegetable oil add to 25g；
9) it is made up of following supplementary materials：
Rifaximin 0.5g, glycerin monostearate 0.25g, suspending agent 0.25g, vegetable oil add to 25g.
In the rifaximin uterus injectant, the vegetable oil is selected from following at least one：Soybean oil, tea oil, corn
Oil, peanut oil and cottonseed oil, preferably soybean oil.
In the rifaximin uterus injectant, the suspending agent is selected from following at least one：Tween 80, sorbester p17 and big
Fabaceous Lecithin, preferably sorbester p17.
In the rifaximin uterus injectant, the particle diameter of the rifaximin bulk drug is 5~10 μm.
The character of rifaximin uterus injectant of the present invention is orange red to dark red oil suspension.
Rifaximin uterus injectant of the present invention can be prepared in accordance with the following steps：It is hard by the vegetable oil, the list
High-molecular compound dicyandiamide solution is made in glycerol and the suspending agent, then the sterile micro mist of the rifaximin is added
Enter, continue agitation grinding and rifaximin uterus injectant is made.
Specifically it may include following steps：
1) after mixing the vegetable oil of partial amount and the glycerin monostearate, heating fusing, mixture is obtained
System；
2) vegetable oil of the suspending agent, the rifaximin and surplus is added into the mixed system, is ground
Mill is uniform, produces the rifaximin uterus injectant.
In above-mentioned preparation method, in step 1), the condition of the heating is：60~80 DEG C heat 15~30 minutes；
The dosage of the vegetable oil is the 40%~60% of the vegetable oil total amount.
In above-mentioned preparation method, in step 2), the grinding is carried out in colloid mill；
Methods described also includes the pre-treatment step of filtering and heat sterilization after step 2)；
The condition of the heat sterilization is：150~160 DEG C sterilize 2~3 hours.
Rifaximin uterus injectant provided by the present invention to cow uteri inflammation (including hysteritis, endometritis,
Uterus suppuration etc.) there is significant curative effect.
Rifaximin uterus injectant of the present invention is clinically used for treating the scorching dosage of cow uteri：1/time.
Compared with prior art, the present invention has the advantages that：
(1) convenient drug administration is quick, reduces substantial amounts of manpower and materials, and animal stress reaction is small, reduces the damage of animal body；
(2) local application, mucosal absorption is poor, and medicine will not enter milk, after medicine, without medicine in the milk of milk cow
Thing remains；
(3) clinically mixed infection situation is more, and compared with conventional cephalo-type uterus injectant, antimicrobial spectrum is wider, more
There is value for clinical application；
(4) simple production process, obtained preparation is uniformly, dispersed, stability is good, is easily enlarged metaplasia production；
(5) for invention formulation for parenteral solution, insoluble drug release is slow, and bioavilability is high, and local organization is pierced
Sharp property is low, and clinical efficacy is notable, has high promotional value.
Embodiment
Experimental method used in following embodiments is conventional method unless otherwise specified.
Material used, reagent etc., unless otherwise specified, are commercially obtained in following embodiments.
Rifaximin uterus injectant provided by the invention is a kind of preparation being evenly distributed, specific preparation method include with
Lower step：
A. by vegetable oil (such as neutral soybean oil) is filtered and heat sterilization after let cool；
B. appropriate pretreated vegetable oil is taken, adds 0.125~1.25g glycerin monostearate；
C.60~80 DEG C heating 15~30 minutes, treat that tristerin melts, after stirring, be cooled to 40 DEG C of left sides
The right side, adds 0.125~1.25g suspending agent (such as sorbester p17), 0.05~0.5g rifaximin (5~10 μm of particle diameter), then mends
It is 25g to add vegetable oil to total amount；
D. grinding is uniform, and rifaximin uterus injectant is made；
F. medicine is fitted into and injected in pipe, sealed, sterilizing, lamp inspection, packaging.
To the detection method of the sedimentation volume ratio of uterus injectant in following embodiments：Apparatus plug graduated cylinder takes test sample
50ml, close plug, firmly shake 1 minute, write down the beginning height H0 of suspension, stand 3 hours, write down the final height of suspended matter
H, it is calculated as follows, it is as a result as follows：Settling ratio volume F=H/H0 is i.e. qualified not less than 0.20.
The method of steriling test：
This product 10 is taken, is put in the separatory funnel of sterilizing, adds 0.1% sterile peptone solution 100ml, with the sterile tetradecane
Isopropyl propionate is washed 4 times, each 200ml, shake well, and water intaking layer is handled with membrane-filter procedure, with sterile NaCl-peptone
Buffer solution (pH7.0) is flushing liquor, and each flushing dose is 100ml, rinses 3 times, checks (annex page 137) in accordance with the law, should meet rule
It is fixed.
The prescription screening of embodiment 1, rifaximin uterus injectant
1st, the screening of glycerin monostearate content (is noted in prescription：Glycerin monostearate abbreviation glyceride in table)
Table 1
Preparation method is as follows：
1) rifaximin aseptic powder is obtained into the sterile micro mist of rifaximin (5~10 μm of particle diameter) through ultramicro grinding；
2) by after filtered (150 DEG C sterilize 3 hours) with heat sterilization of soybean oil, it is placed in standby at room temperature；
3) appropriate pretreated soybean oil is taken, adds tristerin and suspending agent sorbester p17；Heat and stir
(80 DEG C heat 15 minutes), after treating that tristerin melts, adds rifaximin；
5) uniform, obtained rifaximin uterus injectant is ground in sterile colloid mill.
As seen from the results in Table 1, when the content of glycerin monostearate is 0.3% (w/w, g/g), the sedimentation index of product
The requirement of quality standard is not reached；When the content of glycerin monostearate is 0.5~5.0% (w/w, g/g), the items of product
Index reaches the requirement for complying fully with quality standard, it is thus determined that the content of glycerin monostearate is 0.5~5.0% in prescription
(w/w, g/g).
2nd, in prescription Arlacel-80 content screening
Table 2
Preparation method is same as above.
Result as shown in Table 2 is understood, when the content of Arlacel-80 is 0.3% (w/w, g/g), the sedimentation index of product
The requirement of quality standard is not reached；When the mass content of Arlacel-80 is 0.5~5.0% (w/w, g/g), the items of product refer to
Mark is up to the requirement for complying fully with quality standard, it is thus determined that Arlacel-80 content is 0.5~5.0% (w/w, g/g) in prescription.
Embodiment 2, prepare rifaximin uterus injectant
Preparation method is as follows：
1) rifaximin aseptic powder is obtained into the sterile micro mist of rifaximin of 5~10 μm of particle diameter through ultramicro grinding；
2) by after filtered (150 DEG C sterilize 3 hours) with heat sterilization of soybean oil, it is placed in standby at room temperature；
3) appropriate pretreated soybean oil (for the 40%% of the total dosage of soybean oil) is taken, adds glycerin monostearate；
Heat and stir (80 DEG C heat 15 minutes), treat that glycerin monostearate melts, after stirring, be cooled to 40 DEG C, addition department
Disk 80, rifaximin, then soya-bean oil is increased to full dose；
4) uniform, obtained rifaximin uterus injectant is ground in sterile colloid mill.
The character of gained rifaximin uterus injectant is orange red to dark red oil suspension.
The said goods are carried out with settling volume when Sterility testing, it meets the quality standard of uterus injectant.
Embodiment 3, prepare rifaximin uterus injectant
Preparation method is as follows：
1) rifaximin aseptic powder is obtained into the sterile micro mist of rifaximin of 5~10 μm of particle diameter through ultramicro grinding；
2) by after filtered (150 DEG C sterilize 3 hours) with heat sterilization of soybean oil, it is placed in standby at room temperature；
3) appropriate pretreated soybean oil (for the 50% of the total dosage of soybean oil) is taken, adds glycerin monostearate；Add
Heat simultaneously stirs (80 DEG C heat 15 minutes), treats that glycerin monostearate melts, after stirring, is cooled to 40 DEG C, adds sapn
80th, rifaximin, then soya-bean oil is increased to full dose；
4) uniform, obtained rifaximin uterus injectant is ground in sterile colloid mill.
The character of gained rifaximin uterus injectant is orange red to dark red oil suspension.
The said goods are carried out with settling volume when Sterility testing, it meets the quality standard of uterus injectant.
Embodiment 4, prepare rifaximin uterus injectant
Preparation method is as follows：
1) rifaximin aseptic powder is obtained into the sterile micro mist of rifaximin of 5~10 μm of particle diameter through ultramicro grinding；
2) by after filtered (160 DEG C sterilize 2 hours) with heat sterilization of tea oil, it is placed in standby at room temperature；
3) appropriate pretreated soybean oil (for the 60% of the total dosage of soybean oil oil) is taken, adds glycerin monostearate；
Heat and stir (60 DEG C heat 30 minutes), treat that glycerin monostearate melts, after stirring, be cooled to 40 DEG C, addition department
Disk 80, rifaximin, then soya-bean oil is increased to full dose；
4) uniform, obtained rifaximin uterus injectant is ground in sterile colloid mill.
The character of gained rifaximin uterus injectant is orange red to dark red oil suspension.
The said goods are carried out with settling volume when Sterility testing, it meets the quality standard of uterus injectant.
Embodiment 5, prepare rifaximin uterus injectant
Preparation method is as follows：
1) rifaximin aseptic powder is obtained into the sterile micro mist of 5-10 μm of rifaximin of particle diameter through ultramicro grinding；
2) by after filtered (150 DEG C sterilize 2 hours) with heat sterilization of corn oil, it is placed in standby at room temperature；
3) appropriate pretreated corn oil (for the 50% of the total dosage of corn oil) is taken, adds glycerin monostearate；Add
Heat simultaneously stirs (80 DEG C heat 30 minutes), treats that glycerin monostearate melts, and after stirring, is cooled to 40 DEG C, add tween-
80th, rifaximin, then add corn oil to full dose；
4) uniform, obtained rifaximin uterus injectant is ground in sterile colloid mill.
The character of gained rifaximin uterus injectant is orange red to dark red oil suspension.
The said goods are carried out with settling volume when Sterility testing, it meets the quality standard of uterus injectant.
Embodiment 6, prepare rifaximin uterus injectant
Preparation method is as follows：
1) rifaximin aseptic powder is obtained into the sterile micro mist of 5-10 μm of rifaximin of particle diameter through ultramicro grinding；
2) by after filtered (150 DEG C sterilize 2 hours) with heat sterilization of cottonseed oil, it is placed in standby at room temperature；
3) appropriate pretreated cottonseed oil (for the 40%% of the total dosage of cottonseed oil) is taken, adds glycerin monostearate；
Heat and stir (80 DEG C heat 15 minutes), treat that glycerin monostearate melts, after stirring, be cooled to 40 DEG C, add big
Fabaceous Lecithin, rifaximin, then add cottonseed oil to full dose；
5) uniform, obtained rifaximin uterus injectant is ground in sterile colloid mill.
The character of gained rifaximin uterus injectant is orange red to dark red oil suspension.
The said goods are carried out with settling volume when Sterility testing, it meets the quality standard of uterus injectant.
Embodiment 7, prepare rifaximin uterus injectant
Preparation method is as follows：
1) rifaximin aseptic powder is obtained into the sterile micro mist of 5-10 μm of rifaximin of particle diameter through ultramicro grinding；
2) by after filtered (150 DEG C sterilize 2 hours) with heat sterilization of tea oil, it is placed in standby at room temperature；
3) appropriate pretreated tea oil (for the 60% of the total dosage of tea oil) is taken, adds glycerin monostearate；Heating is simultaneously
Stirring (80 DEG C heat 15 minutes), treat that glycerin monostearate melts, after stirring, be cooled to 40 DEG C, add soybean lecithin,
Rifaximin, then add tea oil to full dose；
5) uniform, obtained rifaximin uterus injectant is ground in sterile colloid mill.
The character of gained rifaximin uterus injectant is orange red to dark red oil suspension.
The said goods are carried out with settling volume when Sterility testing, it meets the quality standard of uterus injectant.
Effect test inside embodiment 8, rifaximin uterus injectant
1) safety testing of the rifaximin uterus injectant to milk cow
The scorching healthy cow of 50 postpartum ametrias (inner membrance) is randomly choosed in large-scale milch cow farms, be prepared by embodiment 4
One (25g of rifaximin uterus injectant：Intrauterine slowly 0.1875g) is injected by inseminating tube.Record milk cow mark,
Observing time, date of test and time, per cow head administration before and last time be administered after 1,3,5,7,10 day the output of milk and
The parameters such as body temperature.The clinical symptoms such as cow uteri and vaginal fluid situation are observed by palpation.0 day before administration, last
The 10th day after secondary administration, intrauterine contents row bacteriology checking is gathered.Main separating Escherichia coli, staphylococcus, streptococcus, change
Purulence corynebacteria.Determine that preventing and treating cow uteri (inner membrance) scorching product moves to target according to the above-mentioned data and result of clinical detection of collection
The security of thing.
As a result show, the parameter such as output of milk and body temperature after being administered at each time point before administration with having no significant change, milk
The clinical symptoms such as cattle uterus and vaginal fluid situation.Before administration uterine secretion thing was gathered respectively with the 10th day after administration in 0th
And separation of bacterial, Detection of pathogenic bacteria number reduces compared with before being administered after display administration.Show based on the above results, milk cow is according to recommendation
After single dose gives rifaximin uterus injectant, milk cow is had no adverse reaction, said preparation has higher security.
2) rifaximin uterus injectant residual eliminating in ox body is tested
Milk cow inclusion criteria is that ametria (inner membrance) is scorching and the healthy cow of associated clinical symptoms, milk cow 30 days before the test
Inside not systemic or intrauterine gives antibiotic.The healthy milk of 20 ametrias (inner membrance) inflammation of experimental selection and associated clinical symptoms
Ox, milk cow is normally raised during experiment.Before administration, uterus first is cleaned with physiological saline, rounded plastic pipe is inserted into intrauterine, will
One (25g of rifaximin uterus injectant prepared by embodiment 4:Intrauterine, every ox 0.1875g) are injected by inseminating tube
One.Collection blank milk sample before administration, every ox 6h, 12h, 18h, 24h, 36h, 42h and 48h after last time is administered are gathered
Composite sample 40ml, preserved under the conditions of being placed in -40 DEG C to be measured.Notice that first three milk can not be given up during milking.
Milk sample nitrogen after the extraction of acetonitrile twice dries up, and the purification of HLB solid phase extraction columns is crossed after redissolution, using UPLC-MS-
MS methods detect milk drug concentration.As a result show, through locally be administered after, medicine by the content in blood residuals to milk very
Low, 6h detectable concentrations are 1.25~6.54 μ g/kg to 20 cow heads upon administration, less than the highest residual in milk as defined in European Union
Limitation, and can't detect medicine after all experimental animal 12h.Therefore, said preparation rifaximin uterus injectant is by pushing away
After recommending dosage and recommending course for the treatment of administration, the milk phase of abandoning of milk is 0 day, similar sulfuric acid cephalo-type uterus injectant product (remaining
Auxiliary material is identical) the milk phase is abandoned as 48 hours.
3) rifaximin uterus injectant is to the scorching pharmacodynamics test of cow uteri
Suffer from the scorching milk cow in uterus (inner membrance) in large-scale milch cow farms 40 postpartum of random selection and carry out experiment, be randomly divided into 4
Group, every group 10.Wherein 3 test medicine groups (I, II, III group), give respectively high (2/time), in (1/time), low (1/
2/time) dosage rifaximin uterus injectant；1 drug control group (IV groups), gives Florfenicol uterus injectant 1
Branch.The sample that above-mentioned rifaximin uterus injectant is prepared for embodiment 4, specification 25g：0.187g.
Administration milk cow is observed in detail during whole experiment, record before being administered after on-test, be administered after and be discontinued
Afterwards the performance of each group milk cow clinical symptoms and the generation of symptom, develop, lapse to and Disappearance Scenarios, the body of recording medicine milk cow
The clinical symptoms such as temperature, the output of milk and red, swollen, hot, pain, rectal palpation is carried out to cow uteri, and observation whether there is the clinics such as swelling
Symptom.The 14th day after last time administration, the mucus sample of 1 every cattle uterus neck and vagina is gathered, carries out bacteria distribution training
Support (Escherichia coli, staphylococcus, streptococcus, corynebacterium pyogenes).It is true according to the above-mentioned data and result of clinical detection of collection
The validity of fixed output quota product.
The separation qualification result statistics of the main pathogenic fungi before and after each test group milk cow medication of table 3
According to result of the test, can be drawn a conclusion：
(1) bacteria clearance：After test medicine and control drug administration, before each experimental group milk cow administration and after administration
Main Pathogenic Bacteria quantity changes in uterine secretion thing.Rifaximin uterus injectant high dose group bacteria clearance is 92.8%,
Middle dose group bacteria clearance is 86.7%, low dose group 61.5%, and comparison medicine group is 42.8%.Wherein, middle dose group and
High dose group can obtain satisfactory clinical efficacy, and low dose group forms effective local concentration because drug dose is smaller
Limited, clinical efficacy is general；And comparison medicine (Florfenicol uterus injectant, with the rifaximin uterus injectant of embodiment 4
Composition and each component content are essentially identical, the difference is that only that its bulk drug uses Florfenicol), for single injection, face
Bed curative effect is also unsatisfactory.From the point of view of bacterial species are understood, the medicine is to cow endometritis common pathogen (large intestine bar
Bacterium, streptococcus, staphylococcus aureus and suppurative corynebacteria) it is effective in cure.
(2) milk cow sign is observed：Rifaximin uterus injectant and Florfenicol uterus injectant treatment cow uteri are scorching,
Due to inflammation be present before administration, each experimental group milk cow body temperature slightly raises, and each time point milk cow body temperature gradually recovers after administration
Normally.The spiritual appetite state of milk cow after treatment, secrete milk situation, the various clinical symptoms such as vaginal fluid and uterine state are all
To (P ＜ 0.01) is significantly improved, wherein high, middle dosage rifaximin uterus injectant significant effect is better than low dosage profit good fortune
Former times bright uterus injectant and Florfenicol uterus injectant (P ＜ 0.01), and high, middle dose group therapeutic effect is without significant difference
(P ＞ 0.05).
The test medicine of table 4 and control drug are to cow uteri scorching cure rate and effective percentage
(3) cure rate and effective percentage：High (2 times of recommended doses), in (recommended dose), low (1/2 times of recommended dose) dosage
The rifaximin uterus injectant effective percentage scorching to cow uteri be respectively 90%, 90% and 70%；Note in Florfenicol uterus
It is 60% to the scorching effective percentage of cow uteri to enter agent (control group).In terms of cure rate, high (2 times of recommended doses), in (recommend agent
Amount), the rifaximin uterus injectant of low (1/2 times of recommended dose) dosage be respectively 90% to the scorching cure rate of cow uteri,
80% and 60%；Florfenicol uterus injectant (control group) is 50% to the scorching cure rate of cow uteri.
4) rifaximin uterus injectant is compared with similar products
The rifaximin uterus injectant of table 5 table compared with similar products
The composition and each component content of Cefquinome sulfate uterus injectant are essentially identical, the difference is that only bulk drug
Difference, the bulk drug that Cefquinome sulfate uterus injectant uses is Cefquinome sulfate.
Rifaximin uterus injectant is can be seen that in antimicrobial spectrum, formulation application and medicament residue side from result shown in table 5
Face, there is very prominent advantage compared with cephalo-type product, be more suitable for popularization and application in cow uteri class disease prevention and cure.
Identical test is carried out to embodiment 2,3,5-7 product according to the method for effect test inside embodiment 8, its
As a result it is suitable with the effect of embodiment 4.Show rifaximin uterus injectant provided by the invention safely and effectively, bioavilability
It is high, small to local tissue stimulation, evident in efficacy, there is high promotional value.
Claims (9)
1. a kind of rifaximin uterus injectant, is made up of following supplementary materials：0.05~0.5g of rifaximin, glycerol monostearate
0.125~1.25g of ester, 0.125~1.25g of suspending agent, vegetable oil add to 25g.
2. rifaximin uterus injectant according to claim 1, it is characterised in that：The rifaximin uterus injectant
It is made up of following supplementary materials：0.1~0.5g of rifaximin, 0.125~1.25g of glycerin monostearate, suspending agent 0.125~
1.25g, vegetable oil add to 25g.
3. rifaximin uterus injectant according to claim 1 or 2, it is characterised in that：The vegetable oil is selected from following
It is at least one：Soybean oil, tea oil, corn oil, peanut oil and cottonseed oil.
4. the rifaximin uterus injectant according to any one of claim 1-3, it is characterised in that：The suspending agent choosing
From following at least one：Tween 80, sorbester p17 and soybean lecithin.
5. the rifaximin uterus injectant according to any one of claim 1-4, it is characterised in that：The rifaximin
Particle diameter be 5~10 μm.
6. the preparation method of any rifaximin uterus injectant, comprises the following steps in claim 1-5：
1) after mixing the vegetable oil of partial amount and the glycerin monostearate, heating fusing, mixed system is obtained；
2) vegetable oil of the suspending agent, the rifaximin and surplus is added into the mixed system, grinding is equal
It is even, produce the rifaximin uterus injectant.
7. preparation method according to claim 6, it is characterised in that：In step 1), the condition of the heating is：60~80
DEG C heating 15~30 minutes；
The dosage of the vegetable oil is the 40%~60% of the vegetable oil total amount.
8. the preparation method according to claim 6 or 7, it is characterised in that：In step 2), the grinding is entered in colloid mill
OK；
Methods described also includes the pre-treatment step of filtering and heat sterilization after step 2).
9. rifaximin uterus injectant any one of claim 1-5 is preparing prevention and/or treatment cow uteri inflammation
Application in the medicine of disease.
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
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| CN109432092A (en) * | 2018-12-07 | 2019-03-08 | 中国农业科学院饲料研究所 | A kind of lactation period compounded antibiotic preparation and the preparation method and application thereof |
| CN113842358A (en) * | 2021-10-29 | 2021-12-28 | 佛山市南海东方澳龙制药有限公司 | Novel veterinary uterus injectant and preparation method and application thereof |
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| CN104586855A (en) * | 2014-12-29 | 2015-05-06 | 天津市中升挑战生物科技有限公司 | Compound rifaximin uterus injectant as well as preparation method and application thereof |
| CN104840420A (en) * | 2014-11-18 | 2015-08-19 | 中国农业科学院饲料研究所 | Cefquinome sulfate uterine injectant for milk cows and preparation method of cefquinome sulfate uterine injectant |
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2017
- 2017-07-07 CN CN201710549938.2A patent/CN107334732A/en active Pending
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104840420A (en) * | 2014-11-18 | 2015-08-19 | 中国农业科学院饲料研究所 | Cefquinome sulfate uterine injectant for milk cows and preparation method of cefquinome sulfate uterine injectant |
| CN104586855A (en) * | 2014-12-29 | 2015-05-06 | 天津市中升挑战生物科技有限公司 | Compound rifaximin uterus injectant as well as preparation method and application thereof |
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109432092A (en) * | 2018-12-07 | 2019-03-08 | 中国农业科学院饲料研究所 | A kind of lactation period compounded antibiotic preparation and the preparation method and application thereof |
| CN109432092B (en) * | 2018-12-07 | 2020-06-09 | 中国农业科学院饲料研究所 | Compound antibacterial preparation in lactation period and preparation method and application thereof |
| CN113842358A (en) * | 2021-10-29 | 2021-12-28 | 佛山市南海东方澳龙制药有限公司 | Novel veterinary uterus injectant and preparation method and application thereof |
| WO2023070892A1 (en) * | 2021-10-29 | 2023-05-04 | 佛山市南海东方澳龙制药有限公司 | Novel veterinary uterine infusion, preparation method therefor, and use thereof |
| JP7454288B2 (en) | 2021-10-29 | 2024-03-22 | 佛山市南海東方澳龍製薬有限公司 | Method for preparing a novel veterinary uterine injection |
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Application publication date: 20171110 |