CN108078998B - A kind of tromethamine prostaglandin F2αInjection and preparation method thereof - Google Patents
A kind of tromethamine prostaglandin F2αInjection and preparation method thereof Download PDFInfo
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Abstract
The invention belongs to the technical field of research of animal husbandry breeding, are related to a kind of tromethamine prostaglandin F2αInjection and preparation method thereof.The injection includes tromethamine prostaglandin F per 10ml2α60 70mg, 5 10mg of calcium gluconate, 3 8mg of vitamin D, 1 5mg of vitamin E, 1 10mg of Tween 80,1 5mg of absolute ethyl alcohol, pH adjusting agent：In right amount；The pH adjusting agent is sodium hydroxide solution or/and hydrochloric acid solution, and dosage should adjust the pH value of injection to 7.8 ± 0.2.Calcium gluconate, vitamin E, vitamin D, Tween 80, absolute ethyl alcohol and tromethamine prostaglandin dissolve mixing, after tune pH is 7.8 ± 0.2, are cooled to 30 DEG C or less plus water for injection constant volume, and filling, sterilizing obtains tromethamine prostaglandin F2αInjection.
Description
Technical field
The invention belongs to animal husbandry veterinary arts research fields, are related to a kind of tromethamine prostaglandin F2αInjection and
Preparation method.
Background technology
Estrus synchronization refers to the process of that a group dam heat is controlled and adjusted with certain hormones, is allowed to when scheduled
Interior heat, to carry out large-scale artificial insemination and embryo transfer.In the past few decades, the application of new technology brings milk
The high speed development of ox aquaculture.First, technology of artificial insemination is universal, not only increases reproductive efficiency, is also the kinds such as the output of milk
The raising of matter performance has played great function, and breeds the development and application of hormone and antibiotics new drug so that in major part
Dyssecretosis, infectious breeding difficulty disease are overcome.On the other hand, with the development of milk cattle cultivating appropriate scale of operation,
The new technologies such as estrus synchronization become the effective means for promoting reproductive performance.Mould is managed in the larger modern milk cattle cultivating of cows
Under formula, the implementation of detection, capture and the artificial insemination of heat cow can not be given by the input of increase labour to be solved, and
Sympathize with heat, the application of timing insemination technique that can solve this contradiction.By the artificial adjusting to heat, ovulation, make a group
Milk cow concentrates in the regular period and breeds, and can not only save detection of oestrus this intermediate steps, saves the labour of breeding management, also
The leakage caused by dark heat can be reduced, cow reproduction efficiency is improved.Moreover, using synchronization of Estrus, may be implemented same
Phase breeding, gestation, childbirth, can greatly improve the feeding management of the links such as the gestational period, childbirth, calf breeding and administration of health is movable
Efficiency reduces production cost.At present production unit to milk cow carry out estrus synchronization method there are many kinds of, such as PGF2αOnce-through method,
PGF2αSecondary method, GnRH+PGF2αMethod, CIDR+PGF2αMethod, CIDR+GnRH+PGF2αMethod, spongy embolus+PMSG+PGF2αMethod,
MGA/GnRH/PGF2αMethod, GnRH+PGF2α+ GnRH methods etc..
Natural prostaglandins are actually used due to the features such as stability of molecule is poor, bioactivity range is wide in husbandry sector
Be usually prostaglandin salt or artificial synthesized analog, they often than natural hormone have long action time, life
The advantages that object activity height and Small side effects.Tromethamine prostaglandin F2αIt is artificial synthesized prostaglandin tromethamine salt
Class compound, activity are equivalent to natural prostaglandins F2α100~200 times, tromethamine prostaglandin F2αAs outer
Source property PGF2αFor inducing luteolysis, so that progesterone is generated and reduce or stop, as a result luteal phase is made to shorten, dam is made to do sth. in advance heat
And ovulation, be conducive to breeding, the insemination of the artificial same period or embryo transfer；For lutein cyst or persistence corpus luteum, Huang can be made
Body atrophy is degenerated, and heat and ovulation are promoted.
Invention content
The object of the present invention is to provide a kind of tromethamine prostaglandin Fs2αInjection and preparation method thereof, the amino fourth
Triol prostaglandin F2αInjection has the effect of good regulation and control animals into heat ovulation, realizes animal estrus synchronization.
In order to reach foregoing invention purpose, the present invention uses following technical scheme：
Include tromethamine prostaglandin F per 10ml injections2α60-70mg, calcium gluconate 5-10mg, vitamin D
3-8mg, vitamin E 1-5mg, Tween 80 1-10mg, ethyl alcohol 1-5mg, pH adjusting agent：In right amount；The pH adjusting agent is hydrogen
Sodium hydroxide solution or/and hydrochloric acid solution, dosage should adjust the pH value of injection to 7.8 ± 0.2.
Tromethamine prostaglandin F2αThere are apparent dissolution, current most of research tables to the corpus luteum of animal
It is bright, tromethamine prostaglandin F2αIt acts on lutein cell and the mechanism of luteolysis is caused to be：Tromethamine prostate
Plain F2αIt is combined with the specific receptor (PTGFR) on lutein cell plasma membrane, receptor and the G-protein of activation are coupled, and adjust phosphoric acid flesh
Alcohol pecific phosphorylation enzyme C generates Isosorbide-5-Nitrae, 5- InsP3s (IP3) and diglyceride, since IP3 or receptor activation calcium are logical
Road and make intracellular Ca2+Concentration increases, due to Ca2+With the increase of dialycerides, activated protein kinase C passes through protein kinase C
Effect system and so that progesterone is reduced, also due to activated protein kinase C and intracellular Ca2+Concentration increase causes lutein cells degenerate
And death.
Calcium gluconate can enhance Bone Development for Animals, in addition, part grape as the calcium tonic of animal in injection
Calciofon hydrolysis Ca in body fluid2+, these Ca2+Because of tromethamine prostaglandin F2αThe calcium channel of induction is opened, thus into
Enter intracellular so that intracellular Ca2+Concentration further increases, and assists tromethamine prostaglandin F2αDissolve lutein cell.
Vitamin D can not only promote dam heat and normal oestrous cycle, but also also help the normal development in uterus and ensure son
The normal function in palace.In addition, vitamin D can also adjust blood calcium concentration, make Ca2+In zone of reasonableness.Vitamin D and vitamin E are used
Promote feelings increasing in collaboration to educate.
Preferably, becoming per the group of 10ml injections：Tromethamine prostaglandin F2α67.1mg calcium gluconate
8mg, vitamin D 6mg, vitamin E 3mg, Tween 80 6mg, absolute ethyl alcohol 3mg, pH adjusting agent：In right amount, surplus is injection
Water；
The pH adjusting agent is sodium hydroxide solution or/and hydrochloric acid solution, dosage should adjust the pH value of injection to
7.8±0.2。
In order to reach another object of the present invention, using following technical scheme：A kind of tromethamine prostaglandin F2αNote
The preparation method of liquid is penetrated, the preparation method comprises the following steps：
Vitamin E, vitamin D, Tween 80 and the absolute ethyl alcohol for taking recipe quantity, stir evenly, and the grape of recipe quantity is added
The water for injection of Calciofon and 50-90% recipe quantities, stirs evenly, and the tromethamine prostaglandin of recipe quantity is then added,
Mixing is dissolved, then with sodium hydroxide solution or/and hydrochloric acid solution tune pH is 7.8 ± 0.2,30 DEG C or less is cooled to and adds water for injection
Constant volume, filling, sterilizing obtains tromethamine prostaglandin F2αInjection.
The preparation method further includes ampoule processing：Ampoule is got by production ordering, after taking off outsourcing reason bottle, is sent into wash bottle
Between, first purified water ultrasonic cleaning, is cleaned afterwards with the water for injection of 0.22-0.45 μm of membrane filtration, then through walking speed 40-
300-350 DEG C of conveyer belt of 55Hz, bringing-up section temperature tunnel sterilization drying machine dry sterilization.
Preferably, when dissolving vitamin D and vitamin E, stirred with 50-100rpm rotating speeds under the conditions of 40~80 DEG C
20-40min dissolves mixing.
It is carried out preferably, the tromethamine dinoprost injection of embedding is set in Water bath disinfecting apparatus for ampoules
Sterilizing, sterilize 20-40min at 110-130 DEG C.
After filling injection sterilizing, lamp inspection, labeling and outer packing are carried out, obtains complete salable tromethamine forefront
Parathyrine F2αInjection.
The present invention has the advantages that with the prior art：
(1) tromethamine prostaglandin F of the invention2αInjection includes tromethamine prostaglandin F2α, glucose
Sour calcium, vitamin D, vitamin E, Tween 80 and absolute ethyl alcohol, between each ingredient interaction collaboration promote the dissolving of corpus luteum, make
Atrophy of corpus iuteum is degenerated, and promotes heat and ovulation, while protecting the uterus of animal, promotes breeding fertility.
(2) tromethamine prostaglandin F2αThe preparation method of injection is simple, can carry out filling appearance according to practical application
Amount is adjusted, and realizes industrialized production.
Description of the drawings
Fig. 1 is body temperature ongoing change Dynamic Graph after test ox drug injection in animal safety experiment.
Fig. 2 is Respiration Rate ongoing change dynamic after test ox drug injection in animal safety experiment.
Fig. 3 be animal safety experiment in, after test ox drug injection Pulse Rate through when dynamic change.
Specific implementation mode
Explanation is further described to technical scheme of the present invention below by specific embodiments and the drawings.If without special
Illustrate, the raw material employed in the embodiment of the present invention is raw material commonly used in the art, the method employed in embodiment,
For the conventional method of this field.
Embodiment 1
The tromethamine prostaglandin F of the present embodiment2αInjection, the group per 10ml become：Tromethamine prostate
Plain F2α60.4mg, calcium gluconate 5mg, vitamin D 3mg, vitamin E 3mg, Tween 80 6mg, absolute ethyl alcohol 3mg, pH tune
Save agent：In right amount, surplus is water for injection, pH 7.7.Tromethamine prostaglandin F2αIt is converted to prostaglandin F2α, conversion
Coefficient is 0.7453, i.e., contains 45mg active prostaglandins F per 10ml injections2α。
The ampoule of 10ml is taken, after taking off outsourcing reason bottle, is sent between wash bottle, first purified water ultrasonic cleaning, afterwards with 0.22 μm
The water for injection of membrane filtration cleans, then 300 DEG C of conveyer belt through walking speed 40Hz, bringing-up section temperature tunnel sterilization drying machines are dry
Dry sterilizing.Recipe quantity vitamin E, vitamin D, Tween 80 and absolute ethyl alcohol are taken, is stirred with 70rpm rotating speeds under the conditions of 60 DEG C
20min dissolves mixing, the water for injection of the calcium gluconate and 80% recipe quantity of recipe quantity is added, stirs evenly, is then added
The tromethamine prostaglandin of recipe quantity, is uniformly dissolved, then with 0.5M sodium hydroxide solution tune pH be 7.7, if adjusted,
0.1M hydrochloric acid solutions can be used to adjust back, be cooled to 30 DEG C or less plus water for injection is settled to 20L, through 0.45 μm and 0.22 μm of polyether sulfone
It is qualified that film secondary filtration to visible foreign matters detect.By tromethamine prostaglandin F2αLiquid embedding to ampoule, loading amount is not less than
10.5ml, by the tromethamine prostaglandin F of embedding2αInjection is set in Water bath disinfecting apparatus for ampoules and sterilizes, sterilizing ginseng
Number is 115 DEG C of sterilizing 30min, and lamp inspection, labeling and outer packing obtain complete salable tromethamine prostaglandin F2αInjection
Liquid.
Embodiment 2
The tromethamine prostaglandin F of the present embodiment2αInjection, the group per 10ml become：Tromethamine prostate
Plain F2α69.8mg, calcium gluconate 7mg, vitamin D 5mg, vitamin E 3mg, Tween 80 6mg, absolute ethyl alcohol 3mg, pH tune
Save agent：In right amount, surplus is water for injection, pH 7.8.Tromethamine prostaglandin F2αIt is converted to prostaglandin F2α, conversion
Coefficient is 0.7453, i.e., contains 52mg active prostaglandins F per 10ml injections2α。
The ampoule of 20ml is taken, after taking off outsourcing reason bottle, is sent between wash bottle, first purified water ultrasonic cleaning, afterwards with 0.22 μm
The water for injection of membrane filtration cleans, then 300 DEG C of conveyer belt through walking speed 40Hz, bringing-up section temperature tunnel sterilization drying machines are dry
Dry sterilizing.The vitamin E of recipe quantity, vitamin D, Tween 80 and absolute ethyl alcohol are taken, is stirred with 80rpm rotating speeds under the conditions of 70 DEG C
25min dissolves mixing, the water for injection of the calcium gluconate and 90% recipe quantity of recipe quantity is added, stirs evenly, is then added
The tromethamine prostaglandin of recipe quantity, is uniformly dissolved, then with 0.5M sodium hydroxide solution tune pH be 7.8, if adjusted,
0.1M hydrochloric acid solutions can be used to adjust back, be cooled to 30 DEG C or less plus water for injection is settled to 20L, through 0.45 μm and 0.22 μm of polyether sulfone
It is qualified that film secondary filtration to visible foreign matters detect.By tromethamine prostaglandin F2αLiquid embedding to ampoule, loading amount is not less than
20.6ml, by the tromethamine prostaglandin F of embedding2αInjection is set in Water bath disinfecting apparatus for ampoules and sterilizes, sterilizing ginseng
Number is 120 DEG C of sterilizing 35min, and lamp inspection, labeling and outer packing obtain complete salable tromethamine prostaglandin F2αInjection
Liquid.
Embodiment 3
The tromethamine prostaglandin F of the present embodiment2αInjection, the group per 10ml become：Tromethamine prostate
Plain F2α67.1mg, calcium gluconate 8mg, vitamin D 6mg, vitamin E 3mg, Tween 80 6mg, absolute ethyl alcohol 3mg, pH tune
Save agent：In right amount, surplus is water for injection, pH 7.8.Tromethamine prostaglandin F2αIt is converted to prostaglandin F2α, conversion
Coefficient is 0.7453, i.e., contains 50mg active prostaglandins F per 10ml injections2α。
The ampoule of 10ml is taken, after taking off outsourcing reason bottle, is sent between wash bottle, first purified water ultrasonic cleaning, afterwards with 0.22 μm
The water for injection of membrane filtration cleans, then 300 DEG C of conveyer belt through walking speed 40Hz, bringing-up section temperature tunnel sterilization drying machines are dry
Dry sterilizing.The vitamin E of recipe quantity, vitamin D, Tween 80 and absolute ethyl alcohol are taken, is stirred with 100rpm rotating speeds under the conditions of 50 DEG C
30min is mixed, mixing is dissolved, the water for injection of the calcium gluconate and 90% recipe quantity of recipe quantity is added, stirs evenly, is then added
The tromethamine prostaglandin for entering recipe quantity, is uniformly dissolved, then with 0.5M sodium hydroxide solution tune pH be 7.8, if adjust
It crosses, 0.1M hydrochloric acid solutions can be used to adjust back, be cooled to 30 DEG C or less plus water for injection is settled to 20L, it is poly- through 0.45 μm and 0.22 μm
It is qualified that ether sulfone film secondary filtration to visible foreign matters detect.By tromethamine prostaglandin F2αLiquid embedding is to ampoule, and loading amount is not
Less than 10.5ml, by the tromethamine prostaglandin F of embedding2αInjection is set in Water bath disinfecting apparatus for ampoules and sterilizes, and goes out
Bacterium parameter is 120 DEG C of sterilizing 35min, and lamp inspection, labeling and outer packing obtain complete salable tromethamine prostaglandin F2α
Injection.
Comparative example 1
Difference lies in tromethamine prostaglandin F of the comparative example 1 per 10ml injections with embodiment 3 for comparative example 12α
For 77.8mg, it is converted to active prostaglandin F2αIt is other same as Example 3 for 58mg.
Comparative example 2
Comparative example 2 and embodiment 3 difference lies in, do not include calcium gluconate in the injection of comparative example 2, it is other with it is real
It is identical to apply example 3.
Comparative example 3
Difference lies in do not include vitamin D, other and implementation in the injection of comparative example 3 to comparative example 3 with embodiment 3
Example 3 is identical.
By the tromethamine prostaglandin F of embodiment 1-3 and comparative example 1-32αThe experiment of injection progress muscle irritation,
Animal safety experiment, the test of estrus synchronization effect test.Test tromethamine prostaglandin F of the present invention2αThe peace of injection
Full property and promotion heat effect.
1, muscle irritation is tested
After investigating rabbit intramuscular injection embodiment 1-3 and the injection of comparative example 1, thorn caused by injection site in 48h
Swash reaction and other adverse reactions.
8 Healthy female rabbit are selected in experiment.With aseptic procedure, left side quadriceps muscle of thigh injects embodiment 1 to rabbit 1-4 respectively
Tromethamine prostaglandin F2αInjection 1ml, right side quadriceps muscle of thigh inject the tromethamine prostaglandin F of comparative example 12α
Injection 1ml, rabbit 5-8 inject the tromethamine prostaglandin F of embodiment 2 with aseptic procedure difference left side quadriceps muscle of thigh2αNote
Liquid 1ml is penetrated, right side quadriceps muscle of thigh injects the tromethamine prostaglandin F of embodiment 32αInjection 1ml, is administered once, normal to supply
Feed and water are answered, animal is put to death after 48h, visually observing intramuscular injection site by 1 standards of grading of table, whether there is or not hyperemia, oedema, denaturation
With the stimulation phenomenon such as necrosis, and scored according to the degree of stimulate the reaction.Medicine-feeding part is taken after observation, with 100mg
ML-1 formaldehyde is fixed, slice, HE dyeing, and whether there is or not the pathology such as bleeding, inflammatory cell infiltration between (10 × 10) observation flesh under microscope
Variation.Overall merit is carried out to drug muscle irritation degree according to macroscopic scoring and histopathological examination result,
Standards of grading are shown in Table 1.Experimental result refers to table 2
1 muscle irritation of table visually observes standards of grading
| The order of reaction | Stimulate the reaction |
| 0 | Medicine-feeding part is without significant reaction |
| 1 | Medicine-feeding part musculature mild hyperaemia, range is in 0.5cm × 1.0cm or less |
| 2 | Medicine-feeding part musculature moderate is congested, and range is in 0.5cm × 1.0cm or more |
| 3 | Medicine-feeding part severe is congested, red and swollen, muscle has denaturation |
| 4 | There is the denaturation of muscle brown, necrosis, diameter is in 0.5cm or less |
| 5 | There is large stretch of necrosis in muscle serious degenerative |
Note：The average response score value of 4 rabbit is believed that when being less than 2 meets regulation, as between average response score value 2~3
When, 4 rabbit retrials (8 rabbit can COMPREHENSIVE CALCULATING) should be separately taken, criterion is the same；Such as larger than 3 are thought against regulation,
It is not used for intramuscular injection.
Medicine-feeding part appraisal result is tested in the muscular irritation of 2 injection of table
It visually observes:Different time quadriceps muscle of thigh surface has no apparent hyperemia after injection, red and swollen, and rabbit activity is normal.Family
Rabbit muscle injects 48h after embodiment 1-3 injections, and anatomic observation medicine-feeding part quadriceps muscle of thigh is shown no obvious abnormalities, and it is 0 to score
Grade, 48h after 1 injection of rabbit intramuscular injection comparative example, medicine-feeding part musculature mild hyperaemia, range is in 0.5cm × 1.0cm
Hereinafter, scoring is 1 grade, it is believed that meet regulation.Histopathologic examination:Rabbit quadriceps muscle of thigh muscle fiber band is clear,
Structural integrity is showed no apparent pathology between flesh without bleeding, without the pathological changes such as inflammatory cell infiltration, embodiment 1-3 and comparative example 1
Variation.Illustrate the tromethamine prostaglandin F of the present invention2αInjection has no obvious irritation to rabbit quadriceps muscle of thigh.
2, animal safety is tested
For the safety that confirmation said preparation is applied on target animals ox, this experiment is implemented.Evaluate the amino fourth of the present invention
Triol PGF2αWhether injection generates harmful effect during handling milk cow to milk cow physical signs, production performance.
12 cows are selected in experiment, and in postpartum 60-80d, normal lactation, gestation is not overall, and daily veterinary inspection confirms
For health.10 cows are divided into 2 groups-test group and control group, every group 5, the note of test group 5 embodiments 3 of every beef injection
Penetrate liquid (5 times that recommend injection dosage), every beef injection co-content physiological saline of control group.The feeding environment of test ox, feed,
Way to manage etc. is consistent.The time that cow carries out drug injection is referred to as " 0 day ", the sight for carrying out each Testing index in 0~10 day
Examine the sampling of measurement and biochemical indicator detection sample.
At the 0th, 1,2,3,4,6,10 day of injection drug, one day early, middle and late each primary, and ox is measured only by determined method
Body temperature, breathing, heart rate.As a result as shown in Fig. 1-3.Body temperature, IE ratio and the pulse frequency of all test ox only are in have
The measured value of the in a few days fluctuation of rule, morning is less than noon and dusk.Wherein, body temperature is between 37.55-38.66 DEG C, breathing
For number between 15.2-32.6 beats/min, pulse does not find normal physiologic values range between 59.2-74.2 beats/min
Extremists.After comparative drug injection in 1 day test ox physical signs value processing group difference, it is found that test group ox only exists
Dusk (after injection about 4 hours) on the day of drug injection, there are one the trend of raising, 38.66 ± 0.24 DEG C of average out to, compared with control group
38.32 ± 0.44 DEG C be only higher by 0.34 DEG C, but the not up to significance level of difference, and between two groups of noon next day substantially
Unanimously.On the day of drug injection at dusk, the respiratory rate of test group and control group be respectively 26.4 ± 5.6 beats/min and 27.2 ±
4.0 beats/min, pulse frequency is respectively 69.6 ± 6.3 beats/min and 71.6 ± 9.3 beats/min, without significant difference.
At the 0th, 1,3,6,10 day of injection, 10ml blood is extracted from jugular vein, is placed in the test tube containing blood anticoagulant
In, carry out five classification and Detection of blood routine using Blood Physiological Indexes analyzer.Test result is as indicated at 3.
3 blood routine of table, five classification and Detection result statistical form
White blood cell count(WBC) (WBC) index occurs increasing phenomenon after drug injection, the 1st day after drug injection, tests
The measured value of group is significantly higher than control group (13.66 ± 2.22 × 109/L vs, 9.22 ± 3.97 × 109/L), and it is aobvious to reach difference
The level of work (P<0.05), but on day 2 difference is not notable later.Among white cell component, occur raised being only neutral grain
Cell (NEU), the 1st day test group and the measured value of control group are respectively 4.95 ± 2.38 × 109/L and 1.39 after drug-treated
± 0.21 × 109/L is in significant difference (p<0.05).Other all indexs in five classification and determination index of blood, test group with it is right
According to significant difference is not present between group, also without discovery because significant change occurs for drug injection.
3, estrus synchronization effect test
105 cows are selected, postpartum 60-80d is in, exclude to suffer from endometritis, investigation through veterinary health inspection
Production and Breeding notes confirm in nonpregnant and normal lactation state.105 are randomly divided into 7 groups for examination ox, every group 15, this
The physiological saline of 7 groups of injections for injecting 10ml embodiments 1-3 and comparative example 1-3 respectively and same volume.The raising of each group
Environment, feed, way to manage etc. are consistent.Drug injection is referred to as " 0 day " for trying the time point of ox, injects 48- after drug
Detection of oestrus is carried out within 72 hours, and artificial insemination breeding is carried out to heat milk cow.
Medication handle 24 hours after start, to test ox only daily early, middle and late point 3 times observation heat performance, as mounting,
Vaginal orifice flush, movement increase, vaginal orifice flows out mucus, are determined as external heat.When find vaginal orifice largely flow out hyalomucoid, lead thread
Property it is strong, be in " Y " shape when, implement ovary character examination per rectum, is subsided with corpus luteum on ovary, have diameter more than 8mm advantage ovum
Bubble is criterion, comprehensive judgement heat.Ox to judging heat only carries out uterus pull in the side of advantageous follicular development
Portion's semen deposition.The ox for being accredited as heat after drug-treated in 48-96 hours, and being bred in due course only, charges to estrus synchronization cow
Quantity.The number of cows of heat divided by the interior total head number of group, ratio conduct in 48-96 hours after drug-treated in one processing group
Synch capture transfer.Test result is as shown in table 4.
4 each group milk cow synch capture transfer statistical result of table
Diagnosis of early gestation is carried out using B ultrasound within 35 days after breeding, pregnancy failure ox is transferred to the cows to be matched of normal production programme,
Fertilization ox, which is retained in experiment cows, to continue to observe the generation whether there is or not abortion situation.60 days rectum detection methods carry out gestation after breeding
Identification calculates 60 days conception rates.Conception rate computational methods are within 60 days：It is examined by rectum when in one processing group 60 days after breeding
Look into the ratio that pregnant ox head number accounts for rutting head number of being confirmed as.Test result is as shown in table 5.
60 days conception rate statistical results after the breeding of 5 each group of table
Each group randomly chooses 5 test ox, at the 0th, 1,2,3,4 day of injection drug, collects milk sample 20ml, -20 DEG C of guarantors
It deposits, sepg whey, progesterone content is detected using chemoluminescence method.The results are shown in Table 6.
Progesterone content drug-treated is front and back in 6 milk of table changes (unit：nmol/L)
| Sampling time | D0 | D1 | D2 | D3 | D4 |
| Embodiment 1 | 11.65±4.45 | 1.93±0.53 | 1.95±0.67 | 1.89±1.15 | 1.91±0.78 |
| Embodiment 2 | 12.02±3.22 | 1.82±0.57 | 1.77±0.67 | 1.82±0.89 | 1.83±0.72 |
| Embodiment 3 | 11.21±5.42 | 1.45±0.42 | 1.46±0.51 | 1.50±0.87 | 1.47±0.76 |
| Comparative example 1 | 10.81±4.25 | 2.73±0.71 | 2.51±0.67 | 2.55±0.68 | 2.52±0.83 |
| Comparative example 2 | 11.26±5.31 | 3.69±0.62 | 2.78±0.73 | 2.67±0.68 | 2.61±0.86 |
| Comparative example 3 | 10.92±5.89 | 3.21±0.68 | 2.64±0.75 | 2.58±0.68 | 2.50±0.93 |
| Physiological saline | 10.67±6.55 | 18.01±8.17 | 11.431±8.14 | 12.91±9.42 | 12.99±7.58 |
After injecting drug, progesterone content is remarkably decreased in the milk of test group, and embodiment 1-3 average values maintain
The reduced levels of 2.0nmol/L or so, relatively, a little higher than embodiment group of progesterone level of comparative example 1-3 injects physiology salt
There is no significant changes before milk cow and injection after water.
The tromethamine PGF of the embodiment of the present invention2αInjection has no obvious irritation to rabbit quadriceps muscle of thigh, pacifies to milk cow
Entirely, harmful effect not will produce to its physical signs, production performance, cow oestrus rate, conception rate, and drug effect can be effectively improved
Import drugs level can be reached.
In addition, right in place of the non-limit of claimed technical scope midrange and in embodiment technical solution
The same replacement of single or multiple technical characteristics is formed by new technical solution, equally all in claimed model
In enclosing；Simultaneously the present invention program it is all enumerate or unrequited embodiment in, parameters in the same embodiment are only
Indicate an example (i.e. a kind of feasible scheme) for its technical solution.
Specific embodiment described herein is only an example for the spirit of the invention.Technology belonging to the present invention is led
The technical staff in domain can do various modifications or supplement to described specific embodiment or substitute by a similar method, but simultaneously
The spirit or beyond the scope defined by the appended claims of the present invention is not deviated by.
Claims (5)
1. a kind of tromethamine prostaglandin F2αInjection, which is characterized in that before every 10 ml injections include tromethamine
Row parathyrine F2α60-70 mg, calcium gluconate 5-10 mg, vitamin D 3-8 mg, vitamin E 1-5 mg, Tween 80 1-
10mg, absolute ethyl alcohol 1-5mg, pH adjusting agent：In right amount；
The pH adjusting agent is sodium hydroxide solution or/and hydrochloric acid solution, dosage should adjust the pH value of injection to 7.8 ±
0.2。
2. a kind of tromethamine prostaglandin F according to claim 12αInjection, which is characterized in that every 10 ml notes
Penetrating the group of liquid becomes：Tromethamine prostaglandin F2α67.1 mg, 8 mg of calcium gluconate, 6 mg of vitamin D, vitamin
E 3mg, Tween 80 6mg, absolute ethyl alcohol 3mg, pH adjusting agent：In right amount, surplus is water for injection；
The pH adjusting agent is sodium hydroxide solution or/and hydrochloric acid solution, dosage should adjust the pH value of injection to 7.8 ±
0.2。
3. a kind of tromethamine prostaglandin F as described in claim 1-2 is any2αThe preparation method of injection, feature
It is, the preparation method comprises the following steps：
Vitamin D, vitamin E, Tween 80 and the absolute ethyl alcohol for taking recipe quantity, stir evenly；The gluconic acid of recipe quantity is added
The water for injection of calcium and 50-90% recipe quantities, stirs evenly, and the tromethamine prostaglandin F of recipe quantity is then added2α, dissolving
Mixing, then with sodium hydroxide solution or/and hydrochloric acid solution tune pH be 7.8 ± 0.2, be cooled to 30 DEG C hereinafter, plus water for injection it is fixed
Hold, filling, sterilizing obtains tromethamine prostaglandin F2αInjection.
4. a kind of tromethamine prostaglandin F according to claim 32αThe preparation method of injection, which is characterized in that
When dissolving vitamin E and vitamin D, 20-40min is stirred with 50-100rpm rotating speeds under the conditions of 40~80 DEG C, dissolves mixing.
5. a kind of tromethamine prostaglandin F according to claim 32αThe preparation method of injection, which is characterized in that
The sterilizing is the 20-40min that sterilizes at 110-130 DEG C.
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Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1301178A (en) * | 1998-06-17 | 2001-06-27 | 法玛西雅厄普约翰美国公司 | Solution comprising prostaglandins and benzyl alcohol |
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2017
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Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1301178A (en) * | 1998-06-17 | 2001-06-27 | 法玛西雅厄普约翰美国公司 | Solution comprising prostaglandins and benzyl alcohol |
Non-Patent Citations (2)
| Title |
|---|
| STUDIES CONCERNING THE HORMONAL INDUCTION OF LACTOGENESIS BY PROSTAGLANDIN F2α IN PREGNANT RATS;LEONARDO E. BUSSMANN et al;《Journal of Steroid Biochemistry》;19791231;第11卷;第1485页摘要，右栏第2段 * |
| 氨基丁三醇前列腺素Ｆ２α在奶牛体内的药代动力学研究;袁富威，等;《中国兽医学报》;20170531;第37卷(第5期);第883-887页 * |
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