CN109260208A - A kind of Altrenogest preparation for animals and preparation method thereof - Google Patents
A kind of Altrenogest preparation for animals and preparation method thereof Download PDFInfo
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Abstract
The present invention relates to a kind of Altrenogest preparations for animals and preparation method thereof, belong to veterinary drug technical field.Altrenogest preparation for animals of the invention is by including that the raw material of following mass percent is made, 0.3~0.5% Altrenogest, 0.9~1.1% benzyl alcohol, 0.012~0.016% antioxidant, 0.06~0.38% beta carotene, 0.07~0.25% omega-fatty acid.Altrenogest preparation good absorption effect of the invention, bioavilability are high, formulation disperses effect is good.
Description
Technical field
The invention belongs to veterinary drug technical field, it is related to a kind of Altrenogest preparation for animals and preparation method thereof.
Background technique
Altrenogest is a kind of 21 carbon steroid progestational hormone of triolefin of synthesis, belongs to 19- demethyl-stosterone, is a kind of
Oral active progestational hormone.As all steroids, Altrenogest fat-soluble can be infiltrated through in target cell so by itself
It plays a role in conjunction with special receptor afterwards, inhibits the release of promoting sexual gland hormone to be similar to the binding mode of Natural progesterone.
Altrenogest makes ovarian follicle (> 20~25 millis increased by inhibiting the concentration of endogenous promoting sexual gland hormone LH and FSH in blood
Rice) it shrinks back, and then block heat and ovulation.Followed by it will appear after all increase ovarian follicles are shunk back in the rear half stage of medication
The peak of one FSH secretion, this will starting new round ovarian follicular growth and maturation.Phase meeting follower LH secretion has rule after the treatment
The increase of rule promotes the growth and maturation of ovarian follicle.This endocrine effect can be such that treated young dam enters after drug withdrawal
Heat, therefore Altrenogest can be used for domestic animal synchronization of Estrus.Estrus synchronization can be such that domestic animal delivery time concentrates, convenient for concentrating
Feeding concentrates wean, all-in and all-out, the same period to enter next breeding cycle, effectively improves the breeding potential of domestic animal, reduces cause of disease
Propagation, carry out stringent epidemic prevention system and guarantee Biosecurity system, be conducive to scale management.
It there is no Altrenogest preparation in China's veterinary markets at present, European EMA and U.S. FDA approved Altrenogest
Synchronization of estrus for induction of mare and sow.Since Altrenogest has oil-soluble, have in the prior art Altrenogest is molten
The precedent of oil-type oral medicine is made in vegetable oil, however this department finds in the research and preparation process to Altrenogest,
Although Altrenogest can by itself it is fat-soluble can infiltrate through in target cell, infiltrative limited efficacy, cause its biology
Availability is low, dosage is larger, drug cost is high etc., greatly limits it in the application of veterinary clinic；And Altrenogest oil
Dosage formulation during the preparation process, Altrenogest be first be made powder then redisperse be dissolved in finish, more due to powder
It is tiny, it is be easy to cause reunion, is not easy evenly dispersed.
Summary of the invention
The purpose of the present invention is in view of the above-mentioned problems existing in the prior art, propose a kind of good absorption effect, biology benefit
The Altrenogest preparation for animals that expenditure is high, formulation disperses effect is good.
Object of the invention can be realized by the following technical scheme:
A kind of Altrenogest preparation for animals, the Altrenogest preparation for animals is by the raw material system including following mass percent
At,
Altrenogest: 0.3~0.5%,
Benzyl alcohol: 0.9~1.1%,
Antioxidant: 0.012~0.016%,
Beta carotene: 0.06~0.38%,
Omega-fatty acid: 0.07~0.25%,
Finish: surplus.
Beta carotene and omega-fatty acid is added in the present invention in Altrenogest preparation, and the two can be with animal body lactones
The interaction such as matter lipoprotein, cholesterol, phosphatide influences the rouge distribution of cell membrane surface, cell membrane is made to be more suitable for Altrenogest
Into Altrenogest is absorbed and utilized to improve target cell.
Preferably, further including 0.05~0.23% vitamin E in the raw material of the Altrenogest preparation for animals.
Vitamin E can improve cell membrane lipid metabolic condition in the present invention, maintain endocrine normal function, cooperate with β-
Carrotene and omega-fatty acid play a role.Meanwhile vitamin E can promote dissolution of the Altrenogest in finish.
Preferably, the antioxidant is tertiary butyl-4-hydroxy anisole (BHA) and 2,6-di-tert-butyl p-cresol
(BHT) mixture, the finish are that peanut oil, soybean oil, castor oil or palm oil are any one or more of.
Further preferably, the finish is soybean oil.
Preferably, Altrenogest preparation for animals of stating be made of the raw material of following mass percent,
Altrenogest: 0.4%,
Benzyl alcohol: 1.04%,
BHA:0.007%,
BHT:0.007%,
Beta carotene: 0.21%,
Omega-fatty acid: 0.17%,
Finish: surplus.
Another object of the present invention is to provide a kind of preparation method of Altrenogest preparation for animals, the preparation method packets
Include following steps:
S1, after taking the 25~30% of finish total weight to be cooled to 50~70 DEG C, antioxidant and benzyl alcohol is added, stirring is equal
It is even, obtain oil solution；
S2, after being pre-processed Altrenogest, after oil solution is cooled to 40 DEG C or less, pretreated allyl is added
Pregnant element and other outer raw materials of degreaser, stir evenly, obtain primary medical fluid；
S3, primary medical fluid is added in remaining finish, is stirred evenly, obtain secondary medical fluid；
S4, by secondary medical fluid respectively through 50.0 μm, 30.0 μm of filter membrane secondary filtrations, obtain Altrenogest preparation.
It is kept in whole preparation process of the present invention under the conditions of lower temperature, can effectively prevent hot conditions to raw material
The destruction of each component, and reduce energy consumption and production cost and the requirement to process equipment；Especially in step S2
It is middle that whipping temp is reduced to 40 DEG C hereinafter, the destruction in hot conditions to Altrenogest can be effectively prevent, improve allyl
The drug effect of pregnant element preparation.
Preferably, in the step S1, temperature when stirring is 50~70 DEG C, and mixing speed is 80~120rpm, is stirred
Mixing the time is 5~10min.
Preferably, the pretreatment is ultrasonically treated 2- for Altrenogest to be added in ethyl alcohol in the step S2
It is filtered after 5min.
Altrenogest powder is added directly into finish since particle is tiny, is not easy to disperse, and is easy to reunite, is needed to carry out
Long agitation；The present invention carries out ultrasonic pretreatment using ethyl alcohol before Altrenogest is added to finish, can change alkene
Third pregnant plain surface group, improves dispersion effect and rate of dispersion of the Altrenogest in finish.
Preferably, in the step S2, temperature when stirring is 30~40 DEG C, and mixing speed is 80~120rpm, is stirred
Mixing the time is 10~20min.
Preferably, in the step S3, temperature when stirring is 20~30 DEG C, and mixing speed is 150~200rpm, is stirred
Mixing the time is 10~20min.
Compared with prior art, the invention has the following advantages:
(1) Altrenogest preparation of the invention can effectively adjust livestock endocrine, carry out progestogenic of promoting the sexual maturity, and control livestock is regular
Heat is produced with realizing that livestock grouping is pre-, achievees the purpose that all-in and all-out, so that the production efficiency and industry of livestock be greatly improved
Change management level；
(2) Altrenogest preparation of the invention has preferable bio-absorbable utilization efficiency and effect；
(3) dispersion effect is good during the preparation process for Altrenogest preparation of the invention, shortens preparation time, improves system
Standby efficiency, reduces preparation cost.
Specific embodiment
The following is specific embodiments of the present invention, and technical scheme of the present invention will be further described, but the present invention is simultaneously
It is not limited to these embodiments.
The Altrenogest preparation and preparation method thereof in the present invention is further explained below by specific embodiment.
Examples 1 to 3
Altrenogest preparation for animals in Examples 1 to 3 is made of the raw material including following mass percent,
Altrenogest: 0.3~0.5%,
Benzyl alcohol: 0.9~1.1%,
Antioxidant: 0.012~0.016%,
Beta carotene: 0.06~0.38%,
Omega-fatty acid: 0.07~0.25%,
Finish: surplus.
Antioxidant is the mixture of tertiary butyl-4-hydroxy anisole (BHA) and 2,6-di-tert-butyl p-cresol (BHT), oil
Agent is that peanut oil, soybean oil, palm oil or Miglyol 812 are any one or more of.
Each raw material and its mass percent are as shown in table 1 in Examples 1 to 3.
Table 1: each raw material and its mass percent in Examples 1 to 4
Embodiment 4
(1), by the raw material components and mass percent preparation raw material in embodiment 2, solid material is crossed into 60 mesh standby
With；
(2), after taking the 25% of finish total weight to be cooled to 50 DEG C, antioxidant and benzyl alcohol is added, 50 DEG C of temperature,
5min is stirred under 120rpm revolving speed, obtains oil solution；
(3), Altrenogest is added in ethyl alcohol, is filtered after being ultrasonically treated 2min under 300w power, it is cold to oil solution
But to after 30 DEG C, be added that treated Altrenogest, beta carotene, omega-fatty acid and vitamin E 30 DEG C of temperature,
10min is stirred under 120rpm revolving speed, obtains primary medical fluid；
(4), primary medical fluid is added in remaining finish, stirs 10min under 20 DEG C of temperature, 200rpm revolving speed, obtains
To secondary medical fluid；
(5), secondary medical fluid is obtained into Altrenogest preparation respectively through 50.0 μm, 30.0 μm of filter membrane secondary filtrations.
Embodiment 5
(1), by the raw material components and mass percent preparation raw material in embodiment 2, solid material is crossed into 60 mesh standby
With；
(2), after taking the 30% of finish total weight to be cooled to 60 DEG C, antioxidant and benzyl alcohol is added, 60 DEG C of temperature,
10min is stirred under 100rpm revolving speed, obtains oil solution；
(3), Altrenogest is added in ethyl alcohol, is filtered after being ultrasonically treated 4min under 300w power, it is cold to oil solution
But to after 35 DEG C, be added that treated Altrenogest, beta carotene, omega-fatty acid and vitamin E 35 DEG C of temperature,
15min is stirred under 100rpm revolving speed, obtains primary medical fluid；
(4), primary medical fluid is added in remaining finish, stirs 25min under 30 DEG C of temperature, 180rpm revolving speed, obtains
To secondary medical fluid；
(5), secondary medical fluid is obtained into Altrenogest preparation respectively through 50.0 μm, 30.0 μm of filter membrane secondary filtrations.
Embodiment 6
(1), by the raw material components and mass percent preparation raw material in embodiment 2, solid material is crossed into 60 mesh standby
With；
(2), after taking the 27% of finish total weight to be cooled to 70 DEG C, antioxidant and benzyl alcohol is added, 70 DEG C of temperature,
7min is stirred under 115rpm revolving speed, obtains oil solution；
(3), Altrenogest is added in ethyl alcohol, is filtered after being ultrasonically treated 5min under 300w power, it is cold to oil solution
But to after 35 DEG C, be added that treated Altrenogest, beta carotene, omega-fatty acid and vitamin E in 35 DEG C of temperature, 80rpm
20min is stirred under revolving speed, obtains primary medical fluid；
(4), primary medical fluid is added in remaining finish, stirs 20min under 28 DEG C of temperature, 150rpm revolving speed, obtains
To secondary medical fluid；
(5), secondary medical fluid is obtained into Altrenogest preparation respectively through 50.0 μm, 30.0 μm of filter membrane secondary filtrations.
Embodiment 7~8
Respectively by the raw material components and mass percent preparation raw material in embodiment 1,3, according to the preparation method of embodiment 5
Carry out the preparation of Altrenogest preparation.
Comparative example 1
It is not added with beta carotene, omega-fatty acid and vitamin E, it is other same as Example 5.
Comparative example 2
Omega-fatty acid is substituted using ω -6 fatty acid, it is other same as Example 5.
Comparative example 3
It is not added with vitamin E, it is other same as Example 5.
Comparative example 4
Ultrasonic pretreatment is not carried out to Altrenogest before Altrenogest is added in finish, it is other with 5 phase of embodiment
Together.
Test and performance detection are carried out to product obtained in the embodiment of the present invention and comparative example, it is specific as follows.
(1) dispersion effect is observed
Observe primary medical fluid, secondary medical fluid and final products Altrenogest system obtained in embodiment 4-8, comparative example 1-4
The dispersion effect of agent, as a result as shown in the table:
The dispersion effect of 2 embodiment 4-8 of table, the primary medical fluid in comparative example 1-4 and secondary medical fluid compare
By embodiment 4-8, comparative example 1-4, finally Altrenogest preparation standing obtained is stored in brown bottle, respectively at 5
It finds that the Altrenogest preparation in embodiment 4-8, comparative example 1-3 is right without obvious solids with observation after 10 days
Fine particle shape solid matter in ratio 4 has a small amount of increase.
(2) target cell assimilation effect is tested
It chooses and Altrenogest preparation progress test cell line, experimental method is made in 4-8 of the embodiment of the present invention and comparative example 1-4
It is as follows with result:
Test cell: pig ovary cell
Test method: taking the pig ovary cell that in vitro culture is good, is divided into 8 groups, and every group sets two parallel tests, is cultivating
Pig ovary cell culture solution in add 5mg Altrenogest preparation, respectively at Altrenogest preparation addition after 5min,
The content of Altrenogest in culture solution is detected when 10min, 30min, 240min, culture solution selects DMEM high glucose medium, specifically
As a result as shown in the table:
The assimilation effect of Altrenogest preparation in 3 embodiment 4-8 of table, comparative example 1-4
As shown in Table 3, the Altrenogest concentration in the culture solution in comparative example 1-3 test group of the present invention is in Altrenogest system
Agent be added after 5min, 10min, 30min, 240min when be significantly less than embodiment 5-8, show that allyl is pregnant in comparative example 1-3
Element enters the speed of gonad cell and effect is significantly less than embodiment 5-8, and the present invention can effectively facilitate Altrenogest and enter target
The speed and quantity of cell, bioavilability are high.
(3) pharmacokinetic studies
It chooses and the progress zoopery of Altrenogest preparation is made in the embodiment of the present invention 5,6,7, experimental method and result are such as
Under:
Experimental animal: 8~September age replacement gilt 24 passes through 1~2 oestrous cycle, 95~105kg of weight range,
Test method: replacement gilt is divided into two groups, every group 8, feeds the Altrenogest system in embodiment example 5,6,7 respectively
Agent.
After fasting 12h, material spray administration is carried out by the dosage of 15mg/ days/head (being equivalent to 0.15mg/kg B.W.), is continuously given
Medicine 18 days.Specifically first a feed is divided into two parts when administration, is administered to a copy of it material spray, is supervised after pig eats completely completely again
To an other foddering, guarantee that every pig every time all eats up feed, after administration in first day and the 18th day, respectively after administration
20min, 40min, 1h, 1.5h, 2h, 2.5h, 3h, 4h, 5h, 6h, 8h, 10h, 12h, blood sample is acquired for 24 hours, other blood sampling points are every
(8 a.m.) and 2 pm before day administration after successive administration 18 days, acquired blood sample in the 20th day 2 pm.
Parameters in blood sample after material spray administration for the first time: terminal eliminates half-life period (t1/2), peak time (Tmax), blood medicine
Peak concentration (Cmax), area under the drug-time curve (AUC0-t) and mean residence time (MRT) is as shown in table 2, continuous material spray on the 18th
Each parameter in blood sample after administration: Mean steady state concentration of blood drug (Css), degree of fluctuation, AUC0-tSuch as with mean residence time (MRT)
Shown in table 4.
Table 4: parameters in blood sample after material spray administration for the first time
Table 5: each parameter in blood sample after the continuous administration of material spray on the 18th
By table 4 and table 5 it is found that the peak time of Altrenogest obtained after single-dose in 6-7 of the embodiment of the present invention
(Tmax) comparatively fast, terminal eliminates half-life period (t1/2), mean residence time (MRT) and continuous material spray on the 18th administration after Mean Residence when
Between (MRT) it is relatively long, illustrate Altrenogest preparation of the invention long action time in vivo, while under Drug-time curve
Area (AUC0-t) higher, illustrate bioavilability height.
(4) induction sow estrus synchronization test
Experimental animal: 215 age in days replacement gilts, original body mass, heredity are similar, and through veterinary inspection, behaviouristics, physiology
With the normal healthy replacement gilt 120 of appetite.All experimental animals are fed according to the requirement in growth period with standard mixed fodder,
Nutritional ingredient must not arbitrarily be increased or decreased, carry out feeding management according to a conventional method, carried out before testing necessary immunization inocultation and
Expelling parasite executes stringent Antiepidemic sterilizing measure during test.
Test method:
Sow is randomly divided into 4 groups, I group is respectively tested, tests II group, test III group and negative control group, every group 20
Head, I group of test, II group of test, III group of test are respectively according to alkene obtained in the dosage feeding embodiment 5 of 10mg, 15mg, 30mg
Third pregnant plain preparation, negative control group feed 5ml soybean oil, continuous feeding 18 days.
It lures feelings method to detect oestrus of sow by boar, record heat situation and breeds to heat sow, breeding
Later 23 days, 28 days B ultrasound identification Pregnancies.
Table 6: replacement gilt heat is influenced after Altrenogest feeding
As shown in Table 6, Altrenogest preparation of the invention has the effect of significantly adjusting sow estrus synchronization, with feminine gender
Control group is compared, and Altrenogest preparation of the invention is more preferable in the effect of control oestrus of sow.
Analysis sow most concentrates sow in adjacent two days, 9 days that rutting rate and Altrenogest is concentrated to stop heat after feeding 9 days
Breeding ratio counts the concentration degree of replacement gilt heat, the results are shown in Table 7.
Table 7: Altrenogest stops different time oestrus of sow and breeding situation statistics after feeding
By table 6 and table 7 it is found that Altrenogest preparation of the invention has the effect of significantly promoting to concentrate heat, closing
Under suitable adding proportion, oestrus of sow can be controlled in 2~3 days, test group, comparative example group replacement gilt most concentrate adjacent two
Difference is extremely significant (P < 0.01) compared with negative control group for its heat ratio；Test group significant difference compared with negative control group
(P < 0.05)；Stop feeding in 9 days, respectively compared with negative control group, difference is extremely aobvious for test group, the rutting rate of comparative example group
It writes (P < 0.01).The result shows that Altrenogest preparation can make sow synchronization of estrus, and heat is more concentrated in adjacent 2~3 days.
It analyzing from dosage, the additive capacity of 10mg, 15mg, 30mg have the preferable effect for promoting synchronization of estrus, synchronizing gestation, but
The dosage of 10mg easily causes oral dose insufficient in production application, influences using effect, the dosage higher operating costs of 30mg,
Therefore the dosage of 15mg is more appropriate.
(5) oral acute toxicity testing
Experiment one
Experimental animal: cleaning grade health ICR mouse 40,20 ± 2g of weight, half male and half female is provided by Yangzhou University.
Test method: being divided into first group (20, half male and half female) and second group (20, half male and half female) for mouse, and first
Group is divided into five groups (every group 4, half male and half female) again, respectively according to 100,500,1000,2500,5000mg/kg after fasting 12h
B.w. the Altrenogest preparation in (the pure content of Altrenogest in Altrenogest preparation) five poisoning dosage feeding embodiments 6,
Do not cause death；Second group of mouse is fed with the poisoning dosage of 5000mg/kg b.w. again, is observed continuously after feeding
14 days.
Experiment two
Experimental animal: cleaning grade health ICR rat 40,200 ± 20g of weight, half male and half female is provided by Yangzhou University.
Test method: it carries out, is observed continuously after feeding 14 days according to the method for oral acute toxicity testing one.
Oral acute toxicity testing one and oral acute toxicity testing two are during observation, and mouse and rat clinical manifestation are just
Often, without obvious nervous symptoms, skin and coat are without exception, until the observation period terminates, do not find poisoning and the phenomena of mortality；Experiment knot
Dissect survival mice after beam, internal organs and reproductive organs including Stomach duodenum do not find that obvious eye sees disease
Become.The result shows that Altrenogest preparation of the invention is greater than 5000mg/kg b.w. to the LD50 of passing through mouth of mouse, acute toxicity compared with
It is low.
Specific embodiment described herein is only an example for the spirit of the invention.The neck of technology belonging to the present invention
The technical staff in domain can make various modifications or additions to the described embodiments or replace by a similar method
In generation, however, it does not deviate from the spirit of the invention or beyond the scope of the appended claims.
Claims (8)
1. a kind of Altrenogest preparation for animals, which is characterized in that the Altrenogest preparation is by including following mass percent
Raw material is made,
Altrenogest: 0.3~0.5%,
Benzyl alcohol: 0.9~1.1%,
Antioxidant: 0.012~0.016%,
Beta carotene: 0.06~0.38%,
Omega-fatty acid: 0.07~0.25%,
Finish: surplus.
2. Altrenogest preparation for animals according to claim 1, which is characterized in that the antioxidant is tert-butyl -4- hydroxyl
The mixture of base anisole (BHA) and 2,6-di-tert-butyl p-cresol (BHT), the finish are peanut oil, soybean oil, castor oil
Or palm oil is any one or more of.
3. Altrenogest preparation for animals according to claim 1, which is characterized in that by the raw material system of following mass percent
At,
Altrenogest: 0.4%,
Benzyl alcohol: 1.04%,
BHA:0.007%,
BHT:0.007%,
Beta carotene: 0.21%,
Omega-fatty acid: 0.17%,
Finish: surplus.
4. a kind of preparation method of Altrenogest preparation for animals as described in claims 1 to 3 any claim, feature exist
In the preparation method includes the following steps:
S1, after taking the 25~30% of finish total weight to be cooled to 50~70 DEG C, antioxidant and benzyl alcohol is added, stirs evenly, obtains
To oil solution；
S2, after being pre-processed Altrenogest, after oil solution is cooled to 40 DEG C or less, pretreated Altrenogest is added
It with other raw materials outside degreaser, stirs evenly, obtains primary medical fluid；
S3, primary medical fluid is added in remaining finish, is stirred evenly, obtain secondary medical fluid；
S4, by secondary medical fluid respectively through 50.0 μm, 30.0 μm of filter membrane secondary filtrations, obtain Altrenogest preparation.
5. the preparation method according to claim 4, which is characterized in that in the step S1, temperature when stirring is 50
~70 DEG C, mixing speed is 80~120rpm, and mixing time is 5~10min.
6. the preparation method according to claim 4, which is characterized in that in the step S2, the pretreatment is by allyl
Pregnant element is added in ethyl alcohol, is filtered after being ultrasonically treated 2-5min.
7. the preparation method according to claim 4, which is characterized in that in the step S2, temperature when stirring is 30~
40 DEG C, mixing speed is 80~120rpm, and mixing time is 10~20min.
8. the preparation method according to claim 4, which is characterized in that in the step S3, temperature when stirring is 20~
30 DEG C, mixing speed is 150~200rpm, and mixing time is 10~20min.
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Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN112641737A (en) * | 2020-09-22 | 2021-04-13 | 厦门汇承药业有限公司 | Preparation method of altrenogest chewable tablets |
| CN113350275A (en) * | 2021-06-19 | 2021-09-07 | 江西农业大学 | Altrenogest sustained-release injection and preparation method and application thereof |
| CN113476457A (en) * | 2021-08-03 | 2021-10-08 | 吉林吉力生物技术研究有限公司 | Composition of veterinary altrenogest, veterinary altrenogest soft capsule, preparation method and application thereof |
| CN114344242A (en) * | 2022-01-04 | 2022-04-15 | 北京菲繁生物技术有限公司 | Alsopreglin soft sweets and preparation method thereof |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2016054741A1 (en) * | 2014-10-08 | 2016-04-14 | Arivac Inc. | Altrenogest formulation and uses thereof for estrus synchronisation in animals |
| CN105816466A (en) * | 2016-03-17 | 2016-08-03 | 刘文善 | Veterinary synchronized estrus promoter and preparation method thereof |
| CN105919932A (en) * | 2016-06-13 | 2016-09-07 | 上海同仁药业股份有限公司 | Altrenogest oral liquid and preparation method thereof |
| CN108042485A (en) * | 2017-11-08 | 2018-05-18 | 宁波三生生物科技有限公司 | A kind of Altrenogest preparation and preparation method thereof |
-
2018
- 2018-08-30 CN CN201811000231.7A patent/CN109260208B/en active Active
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2016054741A1 (en) * | 2014-10-08 | 2016-04-14 | Arivac Inc. | Altrenogest formulation and uses thereof for estrus synchronisation in animals |
| CN105816466A (en) * | 2016-03-17 | 2016-08-03 | 刘文善 | Veterinary synchronized estrus promoter and preparation method thereof |
| CN105919932A (en) * | 2016-06-13 | 2016-09-07 | 上海同仁药业股份有限公司 | Altrenogest oral liquid and preparation method thereof |
| CN108042485A (en) * | 2017-11-08 | 2018-05-18 | 宁波三生生物科技有限公司 | A kind of Altrenogest preparation and preparation method thereof |
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN112641737A (en) * | 2020-09-22 | 2021-04-13 | 厦门汇承药业有限公司 | Preparation method of altrenogest chewable tablets |
| CN113350275A (en) * | 2021-06-19 | 2021-09-07 | 江西农业大学 | Altrenogest sustained-release injection and preparation method and application thereof |
| CN113350275B (en) * | 2021-06-19 | 2022-09-06 | 江西农业大学 | Altrenogest sustained-release injection and preparation method and application thereof |
| CN113476457A (en) * | 2021-08-03 | 2021-10-08 | 吉林吉力生物技术研究有限公司 | Composition of veterinary altrenogest, veterinary altrenogest soft capsule, preparation method and application thereof |
| CN114344242A (en) * | 2022-01-04 | 2022-04-15 | 北京菲繁生物技术有限公司 | Alsopreglin soft sweets and preparation method thereof |
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