CN108042485A - A kind of Altrenogest preparation and preparation method thereof - Google Patents
A kind of Altrenogest preparation and preparation method thereof Download PDFInfo
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- A61K31/565—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids not substituted in position 17 beta by a carbon atom, e.g. estrane, estradiol
- A61K31/567—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids not substituted in position 17 beta by a carbon atom, e.g. estrane, estradiol substituted in position 17 alpha, e.g. mestranol, norethandrolone
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- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
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- A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
- A61K47/36—Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
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Abstract
The present invention relates to a kind of Altrenogest preparations and preparation method thereof, belong to veterinary drug technical field.The Altrenogest preparation of the present invention is made of the raw material for including following mass percent, 0.3~0.5% Altrenogest, 0.9~1.1% benzyl alcohol, 0.012~0.016% antioxidant, 3.0~6.5% modified porous chitosan microballs, surplus are finish, and antioxidant is 4 hydroxyanisole of tertiary butyl (BHA) and 2, the mixture of 6 di-tert-butyl p-cresol (BHT), finish are any one of peanut oil, soybean oil, castor oil or palm oil or a variety of；Preparation method is, antioxidant and benzyl alcohol are added in finish, it stirs evenly, adds in Altrenogest and modified porous chitosan microball, stir evenly, obtain primary liquid, primary liquid is added in remaining finish, is stirred evenly, obtains secondary liquid, secondary liquid obtains Altrenogest preparation through membrane filtration.Altrenogest better stability of preparation, the bioavilability of the present invention is high.
Description
Technical field
The invention belongs to veterinary drug technical fields, are related to a kind of Altrenogest preparation and preparation method thereof.
Background technology
Altrenogest is a kind of 21 carbon steroid progestational hormone of triolefin of synthesis, belongs to 19- demethyls-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 is combined to play a role with special receptor afterwards, inhibits the release of promoting sexual gland hormone to be similar to the binding mode of Natural progesterone.
Altrenogest by inhibiting the concentration of endogenous promoting sexual gland hormone LH and FSH in blood, make increased ovarian follicle (>20~25 millis
Rice) it shrinks back, and then block heat and ovulation.In the rear half stage of medication, after all increase ovarian follicles are shunk back, followed by it is present with
The peak of one FSH secretion, this will start new round ovarian follicular growth and maturation.Phase meeting follower LH secretions has rule after the treatment
The increase of rule promotes growth and the 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 concentrate domestic animal delivery time, convenient for concentrating
Wean, all-in and all-out, the same period into next breeding cycle are concentrated in feeding, effectively improve the breeding potential of domestic animal, reduce cause of disease
Propagation, carry out stringent epidemic prevention system and ensure Biosecurity system, beneficial to scale management.
It there is no Altrenogest preparation in China's veterinary markets at present, European EMA and U.S. FDA approved Altrenogest
For the synchronization of estrus of induction of mare and sow.But Altrenogest acid condition and illumination and thermal environment stability inferior compared with
Difference can be subject to certain destruction, in turn result in its low bioavilability, dosage increasing, improve drug cost etc., limit significantly
It is in the application of veterinary clinic.
Chitosan is that a kind of Natural polycations polysaccharide spreads out prepared by sloughing part or all of acetyl group by chitin
Biology.Chitosan has the good characteristics such as nontoxic, biodegradable, is widely used in biotechnology, food, drug, makeup
The fields such as product and medicine.But the activity of chitosan is influenced by factors such as deacetylation itself and molecular weight, most
Dissolubility is poor in number solvent.
The content of the invention
The purpose of the present invention is in view of the above-mentioned problems existing in the prior art, it is proposed that a kind of stability is good, biological utilisation
Spend high Altrenogest preparation and preparation method thereof.
The purpose of the present invention can be realized by following technical proposal：
A kind of Altrenogest preparation, the Altrenogest preparation are made of the raw material for including following mass percent,
Altrenogest：0.3~0.5%,
Benzyl alcohol：0.9~1.1%,
Antioxidant：0.012~0.016%,
Modified porous chitosan microball：3.0~6.5%
Finish：Surplus,
The antioxidant is the mixing of tertiary butyl-4-hydroxy anisole (BHA) and DBPC 2,6 ditertiary butyl p cresol (BHT)
Object, the finish are any one of peanut oil, soybean oil, castor oil or palm oil or a variety of.
The present invention adds modified porous chitosan microball in Altrenogest preparation, and porous structure and chitosan are in itself
Property determine it with larger specific surface area and stronger adsorption capacity, Altrenogest can be adsorbed to the table in its hole
Face as the absorption carrier of Altrenogest, plays a protective role to Altrenogest under hydrochloric acid in gastric juice and photo-thermal environment, and it is pregnant to improve allyl
The stability and bioavilability of plain preparation reduce dosage.Bearer of the modified porous chitosan microball as Altrenogest,
Change Altrenogest into vivo mode and distribution in vivo, the rate of release of Altrenogest can be controlled to make it more preferably
Ground plays effect.Moreover, chitosan surface have substantial amounts of basic group hydroxyl and amino, in gastric acid environment can first with stomach
Acid effect, can further avoid destruction of the hydrochloric acid in gastric juice to Altrenogest.Meanwhile chitosan also has bacteriostatic activity, and do not influence to have
The growth of beneficial bacteria can act synergistically with benzyl alcohol, bacteriostasis is played in Altrenogest preparation.Modified porous chitosan microball
Content is very few, does not have above-mentioned effect, and content can excessively influence the release and absorption of Altrenogest in vivo.Chitosan also has
Good bioactivity and biodegradability, nontoxic and biocompatibility is good, and when use will not damage domestic animal.This
Invention effectively increases its dissolubility in finish by being modified to Porous Chitosan Microspheres so that porous chitosan is micro-
Ball can give full play to its effect.
Benzyl alcohol has preferable fungistatic effect, and can promote dissolving of the Altrenogest in finish and more in modification
Absorption on the chitosan microball of hole makes each component in raw material reach optimal Fusion Strain, so that the drug effect of Altrenogest preparation
Reach optimum state.BHA and BHT has synergistic effect, plays antioxidation, effectively extends effectively making for Altrenogest preparation
Use the phase.
Preferably, the Altrenogest preparation is made of the raw material of following mass percent,
Altrenogest：0.4%,
Benzyl alcohol：1.04%,
BHA：0.007%,
BHT：0.007%,
Modified porous chitosan microball：5.3%,
Finish：Surplus.
Preferably, the surface of the modified porous chitosan microball is connected with aliphatic chain by graft reaction.
The present invention in Porous Chitosan Microspheres surface graft modification by connecting aliphatic chain, aliphatic chain and finish compatibility
Height, and isolation can be formed between chitosan microball, the active group on aliphatic chain can generate connection with Altrenogest
Effect, so as to increase solubility and dispersiveness of the Porous Chitosan Microspheres in finish and the adsorption energy to Altrenogest
Power.
Preferably, the carbon number of the aliphatic chain is between 3~10.
By the carbon number control of aliphatic chain within the above range, reason is that aliphatic chain is long easily in chitosan to the present invention
Microsphere surface causes steric hindrance to act on, and influences the suction-operated to Altrenogest.
Preferably, the grain size of the modified porous chitosan microball is 1~4 μm.
Modified porous chitosan microball grain size is too small, is unfavorable for the absorption of Altrenogest, and is unfavorable for point in finish
It dissipates, grain size is excessive, is unfavorable for release of the Altrenogest in organism and absorbs.
Preferably, the porosity of the modified porous chitosan microball is 52~70%, pore size is 28~53nm.
Suitable porosity and pore size are conducive to the absorption and release of Altrenogest, and aperture is excessive, is unfavorable for allyl
Stability of the pregnant element in gastric acid environment.
Preferably, the finish is soybean oil.
Another object of the present invention is to provide a kind of preparation method of Altrenogest preparation, the preparation method is included such as
Lower step：
S1, after taking the 25~30% of finish total weight to be cooled to 50~70 DEG C, antioxidant and benzyl alcohol are added in, stirring is equal
It is even, obtain oil solution；
S2, after oil solution is cooled to less than 40 DEG C, Altrenogest and modified porous chitosan microball are added in, stirring is equal
It is even, obtain primary liquid；
S3, primary liquid is added in remaining finish, stirred evenly, obtain secondary liquid；
S4, by secondary liquid 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 relatively low temperature conditionss, 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 less than 40 DEG C, it can effectively prevent the destruction in hot conditions to Altrenogest, improve allyl
The drug effect of pregnant element preparation.
Preferably, in the step S1, temperature during stirring is 50~70 DEG C, and mixing speed is 80~120rpm, is stirred
The time is mixed as 5~10min.
Preferably, in the step S2, temperature during stirring is 30~40 DEG C, and mixing speed is 80~120rpm, is stirred
The time is mixed as 20~30min.
Preferably, in the step S3, temperature during stirring is 20~30 DEG C, and mixing speed is 150~200rpm, is stirred
The time is mixed as 20~30min.
Compared with prior art, the invention has the advantages that：
(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 to realize the pre- production of livestock grouping, achievees the purpose that all-in and all-out, so as to which the production efficiency of livestock and industry be greatly improved
Change management level；
(2) Altrenogest preparation of the invention can be maintained at the stability under hydrochloric acid in gastric juice and light and heat condition, can effectively improve
Availability of the storage life and Altrenogest of Altrenogest preparation in organism；
(3) Altrenogest preparation of the invention has certain slow releasing function, can reduce administration number of times, so as to improve work
Efficiency reduces artificial and management cost.
Specific embodiment
It is specific embodiments of the present invention below, technical scheme is further described, but the present invention is simultaneously
It is not limited to these embodiments.
Altrenogest preparation in the present invention and preparation method thereof is further explained below by specific embodiment.
Examples 1 to 4
Altrenogest preparation in Examples 1 to 4 is made of the raw material for including following mass percent,
Altrenogest：0.3~0.5%,
Benzyl alcohol：0.9~1.1%,
Antioxidant：0.012~016%,
Modified porous chitosan microball：3.0~6.5%
Finish：Surplus,
Antioxidant for tertiary butyl-4-hydroxy anisole (BHA) and 2,6-di-tert-butyl p-cresol (BHT) mixture, it is oily
Agent is any one of peanut oil, soybean oil, palm oil or Miglyol 812 or a variety of.
The surface of modified porous chitosan microball is connected with aliphatic chain by graft reaction, and the carbon number of aliphatic chain is 3~10
Between.The grain size of modified porous chitosan microball is 1~4 μm, and porosity is 52~70%, and pore size is 28~53nm.
Each raw material and its mass percent are as shown in table 1 in Examples 1 to 4, the structure ginseng of modified porous chitosan microball
Number is as shown in table 2.
Table 1：Each raw material and its mass percent in Examples 1 to 4
Table 2：The structural parameters of modified porous chitosan microball
Embodiment 5
(1), prepare raw material by the raw material components in embodiment 2 and mass percent, solid material is crossed into 60 mesh sieve standby
With；
(2), after the 25% of finish total weight is taken to be cooled to 50 DEG C, antioxidant and benzyl alcohol are added in, 50 DEG C of temperature,
5min is stirred under 120rpm rotating speeds, obtains oil solution；
(3), oil solution is cooled to 30 DEG C, adds in Altrenogest and modified porous chitosan microball, 30 DEG C of temperature,
30min is stirred under 120rpm rotating speeds, obtains primary liquid；
(4), primary liquid is added in remaining finish, stirs 30min under 25 DEG C of temperature, 150rpm rotating speeds, obtain
To secondary liquid；
(5), secondary liquid is obtained into Altrenogest preparation respectively through 50.0 μm, 30.0 μm of filter membrane secondary filtrations.
Embodiment 6
(1), prepare raw material by the raw material components in embodiment 2 and mass percent, solid material is crossed into 60 mesh sieve standby
With；
(2), after the 30% of finish total weight is taken to be cooled to 60 DEG C, antioxidant and benzyl alcohol are added in, 60 DEG C of temperature,
10min is stirred under 100rpm rotating speeds, obtains oil solution；
(3), oil solution is cooled to 35 DEG C, adds in Altrenogest and modified porous chitosan microball, 35 DEG C of temperature,
25min is stirred under 100rpm rotating speeds, obtains primary liquid；
(4), primary liquid is added in remaining finish, stirs 25min under 30 DEG C of temperature, 180rpm rotating speeds, obtain
To secondary liquid；
(5), secondary liquid is obtained into Altrenogest preparation respectively through 50.0 μm, 30.0 μm of filter membrane secondary filtrations.
Embodiment 7
(1), prepare raw material by the raw material components in embodiment 2 and mass percent, solid material is crossed into 60 mesh sieve standby
With；
(2), after the 27% of finish total weight is taken to be cooled to 70 DEG C, antioxidant and benzyl alcohol are added in, 70 DEG C of temperature,
8min is stirred under 80rpm rotating speeds, obtains oil solution；
(3), oil solution is cooled to 40 DEG C, adds in Altrenogest and modified porous chitosan microball, 40 DEG C of temperature,
20min is stirred under 80rpm rotating speeds, obtains primary liquid；
(4), primary liquid is added in remaining finish, stirs 22min under 20 DEG C of temperature, 200rpm rotating speeds, obtain
To secondary liquid；
(5), secondary liquid is obtained into Altrenogest preparation respectively through 50.0 μm, 30.0 μm of filter membrane secondary filtrations.
Embodiment 8
(1), prepare raw material by the raw material components in embodiment 2 and mass percent, solid material is crossed into 60 mesh sieve standby
With；
(2), after the 26% of finish total weight is taken to be cooled to 65 DEG C, antioxidant and benzyl alcohol are added in, 65 DEG C of temperature,
7min is stirred under 115rpm rotating speeds, obtains oil solution；
(3), oil solution is cooled to 35 DEG C, adds in Altrenogest and modified porous chitosan microball, 35 DEG C of temperature,
25min is stirred under 110rpm rotating speeds, obtains primary liquid；
(4), primary liquid is added in remaining finish, stirs 20min under 28 DEG C of temperature, 180rpm rotating speeds, obtain
To secondary liquid；
(5), secondary liquid is obtained into Altrenogest preparation respectively through 50.0 μm, 30.0 μm of filter membrane secondary filtrations.
Embodiment 9~11
Prepare raw material by the raw material components in embodiment 1,3,4 and mass percent respectively, according to the preparation side of embodiment 6
Method carries out the preparation of Altrenogest preparation.
Comparative example 1
Modified porous chitosan microball is not added in the preparation process of Altrenogest preparation, it is other same as Example 6.
Comparative example 2
The Altrenogest preparation of commercially available other manufacturers.
Stability experiment is carried out using Altrenogest preparation obtained in embodiment, comparative example 1 and comparative example 2 and animal is real
It tests, experimental method and result are as follows：
(1) stability experiment
Experimental method：By the Altrenogest preparation in embodiment 6, comparative example 1 and comparative example 2 respectively at high temperature (60 DEG C) and
Under the conditions of intense light irradiation degree (4500lx ± 500lx), influence factor experiment investigation is carried out, was sampled respectively at the 5th day and the 10th day, is surveyed
Determine content and related substance, the results are shown in Table 3：
3 Altrenogest influence factor result of the test of table
The experimental result of table 3 shows that the Altrenogest preparation stability ratio for being with the addition of modified porous chitosan microball does not add
Modified porous chitosan microball and other commercial product will be got well.Using the allyl prepared in embodiment in the present invention 5,6~11
Pregnant element preparation carries out above-mentioned experiment, and the result of obtained result and embodiment 6 in table 3 approaches.
(2) pharmacokinetic studies
Experimental animal：8~September age replacement gilt 16, by 1~2 oestrous cycle, 95~105kg of weight range,
Test method：Replacement gilt is divided into two groups, every group 8, feeds the Altrenogest in embodiment 6, comparative example 1 respectively
Preparation.
After fasting 12h, material spray administration is carried out by the dosage of 20mg/ days/head (being equivalent to 0.2mg/kg B.W.), is continuously given
Medicine 18 days.First a feed is divided into two parts during specific administration, is administered to a copy of it material spray, is supervised after pig eats totally completely again
To an other foddering, ensure that every pig every time all eats up feed, after administration in first day and the 18th day, after administration
20min, 40min, 1h, 1.5h, 2h, 2.5h, 3h, 4h, 5h, 6h, 8h, 10h, 12h, blood sample is gathered for 24 hours, other blood sampling points are every
(8 a.m.) and 2 pm before day administration, successive administration gather blood sample after 18 days, in the 20th day 2 pm.
Parameters in blood sample after material spray administration for the first time：End eliminates half-life period (t eventually1/2), peak time (Tmax), blood medicine peak
It is worth concentration (Cmax), area under the drug-time curve (AUC0-t) and mean residence time (MRT) is as shown in table 4, continuous material spray on the 18th is given
Each parameter in blood sample after medicine：Mean steady state concentration of blood drug (Css), degree of fluctuation, AUC0-tWith mean residence time (MRT) such as table 5
It is shown.
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
From table 4 and table 5, compared with comparative example 1, Altrenogest obtained is in single-dose in the embodiment of the present invention 6
Peak time (T afterwardsmax) close, and end eliminates half-life period (t eventually1/2), mean residence time (MRT) and continuous material spray on the 18th give
Mean residence time (MRT) is relatively long after medicine, illustrates Altrenogest preparation of the invention long action time in vivo, tool
There are certain slow release effect, while area under the drug-time curve (AUC0-t) higher, illustrate bioavilability height.
(3) experiment of sow estrus synchronization is induced
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,
Arbitrarily must not improve or reduce nutritional ingredient, carry out feeding management according to a conventional method, carried out before testing necessary immunization inocultation and
Expelling parasite performs stringent Antiepidemic sterilizing measure during experiment.
Test method：
Sow is randomly divided into 5 groups, respectively test I group, experiment II group, experiment III group, 1 group of comparative example, 2 groups of comparative example
Drug control group and negative control group, every group 20, experiment I group, experiment II group, experiment III group respectively according to 10mg, 20mg,
Altrenogest preparation obtained in the dosage feeding embodiment 6 of 40mg, 1 group of dosage according to 20mg of comparative example feed comparative example 1
In Altrenogest preparation obtained, 2 groups of drug control groups of comparative example feed the allyl of other manufacturers according to the dosage of 20mg
Pregnant element preparation, negative control group feeding 5ml soybean oils, continuous feeding 18 days.
By boar feelings method is lured to detect oestrus of sow, record heat situation and bred to heat sow, bred
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 apparent effect for adjusting sow estrus synchronization, test group
Between 2 groups of drug control groups of comparative example difference not significantly (P ＞ 0.05), during experiment, test group and comparative example group with it is cloudy
Property control group compare, rutting rate difference not significantly (P ＞ 0.05).Compared with 1 group of comparative example, Altrenogest system of the invention
Agent 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
From table 6 and table 7, Altrenogest preparation of the invention has the apparent effect for promoting to concentrate heat, is 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 notable (P ＜ 0.01) compared with negative control group for its heat ratio；Test group sow most concentrates rutting rate in 9 days
Difference is not notable between comparative example group, but test group, comparative example group significant difference (P ＜ 0.05) compared with negative control group；
Stop feeding in 9 days, test group, the rutting rate of comparative example group are distinguished compared with negative control group, difference extremely significantly (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.From dosage
Upper analysis, the additive capacity of 10mg, 20mg, 40mg have preferable promotion synchronization of estrus, the effect of synchronous gestation, but 10mg
Dosage easily causes oral dose deficiency in production application, influences using effect, the dosage use cost of 40mg is higher, therefore
The dosage of 20mg is more suitable.
(4) 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：Mouse is divided into first group (20, half male and half female) and second group (20, half male and half female), first
Group is divided into as five groups (every group 4, half male and half female), after fasting 12h respectively according to 100,500,1000,2500,5000mg/kg
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 rats 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 apparent nervous symptoms, skin and hair 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 substantially to observe disease
Become.The result shows that Altrenogest preparation of the invention is more than the LD50 of passing through mouth of mouse 5000mg/kg b.w., acute toxicity compared with
It is low.
In conclusion the Altrenogest preparation in the present invention has significantly promote domestic animal estrus synchronization, the same period pregnant
Effect will not cause dam stress reaction, and the modified porous chitosan microball added in formulation process is to Altrenogest
It plays a protective role, the unstability of Altrenogest under hydrochloric acid in gastric juice and light and heat condition can be reduced, improve its utilization in vivo
Degree, and with certain slow release effect, administration number of times and dosage can be reduced.
Specific embodiment described herein is only to spirit explanation for example of the invention.Technology belonging to the present invention is led
The technical staff in domain can do various modifications or additions to described specific embodiment or replace in a similar way
Generation, but without departing from spirit of the invention or beyond the scope of the appended claims.
Claims (10)
1. a kind of Altrenogest preparation, which is characterized in that the Altrenogest preparation is by including the raw material of following mass percent
It is made,
Altrenogest：0.3~0.5%,
Benzyl alcohol：0.9~1.1%,
Antioxidant：0.012~0.016%,
Modified porous chitosan microball：3.0~6.5%
Finish：Surplus,
The antioxidant is the mixture of tertiary butyl-4-hydroxy anisole (BHA) and 2,6-di-tert-butyl p-cresol (BHT), institute
Finish is stated as any one of peanut oil, soybean oil, castor oil or palm oil or a variety of.
2. Altrenogest preparation according to claim 1, which is characterized in that the Altrenogest preparation is by following quality hundred
The raw material of ratio is divided to be made,
Altrenogest：0.4%,
Benzyl alcohol：1.04%,
BHA：0.007%,
BHT：0.007%,
Modified porous chitosan microball：5.3%,
Finish：Surplus.
3. Altrenogest preparation according to claim 1, which is characterized in that the surface of the modified porous chitosan microball
Aliphatic chain is connected with by graft reaction.
4. Altrenogest preparation according to claim 1, which is characterized in that the grain size of the modified porous chitosan microball
For 1~4 μm.
5. Altrenogest preparation according to claim 1, which is characterized in that the hole of the modified porous chitosan microball
Rate is 52~70%, and pore size is 28~53nm.
6. Altrenogest preparation according to claim 1, which is characterized in that the finish is soybean oil.
A kind of 7. preparation method of the Altrenogest preparation as described in claim 1~6 any claim, which is characterized in that institute
The preparation method stated 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 in, stirs evenly, obtains
To oil solution；
S2, after oil solution is cooled to less than 40 DEG C, Altrenogest and modified porous chitosan microball is added in, stirs evenly, obtains
To primary liquid；
S3, primary liquid is added in remaining finish, stirred evenly, obtain secondary liquid；
S4, by secondary liquid respectively through 50.0 μm, 30.0 μm of filter membrane secondary filtrations, obtain Altrenogest preparation.
8. preparation method according to claim 7, which is characterized in that in the step S1, temperature during stirring is 50
~70 DEG C, mixing speed is 80~120rpm, and mixing time is 5~10min.
9. preparation method according to claim 7, which is characterized in that in the step S2, temperature during stirring for 30~
40 DEG C, mixing speed is 80~120rpm, and mixing time is 20~30min.
10. preparation method according to claim 7, which is characterized in that in the step S3, temperature during stirring for 20~
30 DEG C, mixing speed is 150~200rpm, and mixing time is 20~30min.
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