CN105250221B - A kind of Licopyrinobuter dried emulsifier and preparation method thereof - Google Patents
A kind of Licopyrinobuter dried emulsifier and preparation method thereof Download PDFInfo
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- CN105250221B CN105250221B CN201410333823.6A CN201410333823A CN105250221B CN 105250221 B CN105250221 B CN 105250221B CN 201410333823 A CN201410333823 A CN 201410333823A CN 105250221 B CN105250221 B CN 105250221B
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Abstract
The invention belongs to pharmaceutical technology fields, disclose a kind of Licopyrinobuter dried emulsifier and preparation method thereof.Specifically, the present invention provides a kind of Licopyrinobuter dried emulsifier, it includes Licopyrinobuter as active component, oil, emulsifier, water-soluble polymer, filler, corrigent and sweeteners.The present invention also provides the preparation method of the dried emulsifier, the powder of the lotion prepared by the dried emulsifier and spray-dried, rotary evaporation drying preparation the dried emulsifier is dispensed.This dried emulsifier physical property is stablized, and convenience in transport, storage provide rational preparation prescription and preparation process, it is easy to accomplish industrialization for clinical application.
Description
Technical field
The invention belongs to pharmaceutical technology fields, and in particular to a kind of Licopyrinobuter dried emulsifier and preparation method thereof especially relates to
And a kind of Licopyrinobuter oil-in-water type dried emulsifier and its preparation method.
Background technology
6- (4- chlorphenyls) -2,2- dimethyl -7- phenyl -2,3-, bis- hydrogen-baseds-pyrroles mile piperazine -5- acetic acid Butylnitrate esters, English
Literary fame Licopyrinobuter, common name fix tentatively Licopyrinobuter, and chemical structural formula is：
Rheumathritis (rheumatoid arthritis RA) is a kind of crippling stronger systemic autoimmune
Such as not active and effective treatment, the change of joint erosion venereal disease will occur generally in 1 to 2 year for disease.At present, RA treatments are big for two
Class drug, nonsteroidal anti-inflammatory analgetic (NSAIDs) and change course of disease antirheumatic drug (DMARDs).NSAIDs main functions are
Mitigate arthralgia, swelling and the improvement function of joint of RA patient, but its serious adverse reaction to gastrointestinal tract limits its
It uses.To overcome drawbacks described above, Tianjin Inst. of Materia Medica has developed 6- (4- chlorphenyls) -2,2- dimethyl -7- phenyl -2,3- bis-
Hydrogen-based-pyrroles mile piperazine -5- acetic acid Butylnitrate esters, it has compared with strong solution heat, analgesia, Anti-arthritic activity, and discharges nitric oxide
It protects gastrointestinal tract mucous.Non-steroidal anti-inflammatory drugs (NSAIDs) adverse reaction is not only reduced or eliminated, but also with myocardial preservation
Effect, can repair myocardial reperfusion injury.6- (4- chlorphenyls) -2,2- dimethyl -7- phenyl -2,3- bis- hydrogen-baseds-pyrroles mile piperazines -
The pharmaceutical research result of the test of 5- acetic acid Butylnitrate esters shows in 4 anti-inflammation models there is notable anti-inflammatory activity
(ED300.008mmol/kg).In Mouse oral product 5000mg/kg, Beagle dog take orally the anxious poison experiments of product 1000mg/kg,
Have no toxic reaction.30 days product 500mg/kg of rat continuous oral, 20 days product 100mg/kg of Beagle dog continuous oral, have no
With the relevant toxic reaction of drug.It gives product 120mg/kg sensitives period of teratogenesis to test, does not find embryonic development toxicity.In vivo
In environment, serum, gastric mucosa NO amounts dramatically increase after which is administered 1 hour, and NO amounts continue to increase after 3 hours.Pass through pharmacology, medicine
The preliminary tests research such as generation and anxious, long toxicity, it was demonstrated that the compound has pharmaceutical activity.
Because its unique physics and chemical property, particularly its low solubility are not soluble in water.Therefore, although active medicine passes through
After micronization processes, tablet is made, because of the water-insoluble of drug, is still difficult to dissolve out completely, when in capsule or tablet form
During oral medication, Licopyrinobuter is not easily dissolved and disperses, thus cannot absorb rapidly in vivo.This easily reduces its life again
Object availability.
Liquid emulsion belongs to thermodynamic unstable system, and during storage, liquid emulsion is prone to be layered, rupture,
The wild effects such as phase inversion, cause water-oil phase to detach, and emulsion droplet merges or the transformation of emulsion type；It is blended in simultaneously with aqueous medium
Oil together is easy to rotten due to the effect of the light in microorganism, external environment, the oxygen in air and temperature.In addition, liquid
Due to a large amount of moisture in body emulsion, it is micro- to prevent need to usually to add in a certain amount of preservative (such as sodium benzoate, paraben esters)
The pollution of biology.Preservative is well-known the harm of human body.
The technical problems to be solved by the invention are the defects of overcoming Licopyrinobuter drug itself and its are made oral administration solid
The problem of unstable defect existing for preparation and liquid emulsion and low normal oral solid pharmaceutical preparation biological utilisation.There is provided it is a kind of for
Oral dried emulsifier.It therefore, will there is an urgent need in the art to develop the Licopyrinobuter dried emulsifier without preservative of solid state
With good clinical meaning and commercial significance.
Invention content
The object of the present invention is to provide a kind of Licopyrinobuter dried emulsifiers, and it includes as active constituent dose therapeutically effective
Licopyrinobuter, oil, emulsifier, water-soluble polymer, filler, corrigent and sweetener.
It is a further object of the present invention to provide the preparation methods of Licopyrinobuter dried emulsifier.
Dried emulsifier of the present invention its be in solid powdered object or block.The dried emulsifier,
After being redissolved with water, the emulsion droplet average diameter of gained emulsion is less than 5000nm, preferably, 1000~3000nm,
More preferably 500~1500nm.
Dried emulsifier of the present invention includes following parts by weight of component：
A. Licopyrinobuter 0.01~10.0；
B. the weight ratio 1~200.0 of Licopyrinobuter and oil；
C. emulsifier 4.0~30.0；
D. water-soluble polymer 5.0~50.0；
E. filler 20.0~50.0；
The present invention provides a kind of preparation method of the dried emulsifier of Licopyrinobuter, this method includes the following steps：
(1) by Licopyrinobuter dissolution of raw material in oil phase；
(2) emulsifier, water-soluble polymer, filler are dissolved in water, are uniformly dispersed；
(3) (1), (2) are merged, are vortexed, the conventional method that field of medicaments is all known can be used in and completed.For example, it can use
Blender, ultrasonic oscillator, high pressure homogenizer emulsification obtain lotion, and lotion is in oil-in-water bead；
(4) drying of fluid milk can use the conventional drying means all known in field of medicaments to be freezed as being spray-dried
Dry or rotary evaporation, spray drying can use conventional fluidized bed pelletizer.Gained Licopyrinobuter dried emulsifier can be divided
Packaging.The dried emulsifier is solid state, needs that dried emulsifier powder or particle is taken to add in appropriate aqueous medium redisperse and obtain when in use
It is drunk after to lotion.
According to preparation method provided by the invention, Licopyrinobuter described in step (1) is active medicine；The oil phase packet
It includes：Midchain oil, soybean oil, safflower oil, tea oil, olive oil, peanut oil, sesame oil, coconut oil and corn oil.It is preferred that tea oil, again
It is preferred that midchain oil.The weight ratio of wherein described Licopyrinobuter and oil is 1：8 to 1：200 (w/w), preferably 1：8 to 1：150 (w/w),
More preferable 1：8 to 1：100 (w/w), further preferably 1：8 to 1：50(w/w).
According to preparation method provided by the invention, water-soluble polymer includes described in step (2)：Polyvinylpyrrolidine
Ketone, hydroxypropyl methyl cellulose, hydroxypropyl cellulose, polyethylene glycol, water-soluble polypropylene acid copolymer is (for example, Eudragit
E or carbomer), polyvinyl alcohol or its mixture, preferably polyvinylpyrrolidone, hydroxypropyl methyl cellulose, polyethylene glycol or
Its mixture.Most preferably water-soluble polymer hydroxypropyl methyl cellulose.Wherein described water-soluble polymer is dried emulsifier gross weight
5 to 50% (w/w), preferably 10 to 40% (w/w) of amount, in preferably 10 to 30% (w/w).
According to preparation method provided by the invention, water-soluble filler described in step (2) is selected from following one or two
Combination：White granulated sugar, sucrose, mannitol, sorbierite, xylitol, trehalose, maltitol, galactitol, inositol, dextrin, ring paste
Essence (for example, alpha-cyclodextrin, beta-cyclodextrin, gamma-cyclodextrin or hydroxypropylβ-cyclodextrin, particularly hydroxypropylβ-cyclodextrin) and
Mixture.Best, water-soluble sugar can select lactose, mannitol, sucrose.It is preferred that lactose.Wherein described water-soluble filler
It is 20 to 50% (w/w) of dried emulsifier total weight, preferably 25 to 40% (w/w).
According to preparation method provided by the invention, emulsifier described in step (2) is selected from following one or more combinations
Polyethylene glycol, Tween-80, lecithin, cephalin and soybean lecithin.It is preferred that Tween-80, polyethylene glycol.It is it is preferred that poly-
Sorb ester -80, wherein the emulsifier is 4 to 30% (w/w) of weight of oil, preferably 5 to 30% (w/w), more preferable 5 to 20%
(w/w), further preferably 6 to 15% (w/w).
According to preparation method provided by the invention, emulsifier described in step (3), the emulsion droplet arithmetic average of gained emulsion
Diameter is less than 5000nm, preferably, 1000~3000nm, more preferably 500~1500nm.
According to preparation method provided by the invention, emulsifier described in step (4), gained emulsion through rotary evaporation and/
Or it is spray-dried to obtain dried emulsifier.Gained Licopyrinobuter dried emulsifier can carry out subpackage dress.The dried emulsifier is solid state, is being used
When dried emulsifier powder or particle need to be taken to add in after appropriate aqueous medium redisperse obtains lotion drink.The emulsion droplet arithmetic of gained emulsion
Average diameter is less than 5000nm, more preferably preferably 1000~3000nm, 500~1500nm.
Description of the drawings
Fig. 1 is Licopyrinobuter dried emulsifier process flow chart of the present invention.
Specific embodiment
The present invention is further described in detail With reference to embodiment, the embodiment provided is only for explaining
The bright present invention, the range being not intended to be limiting of the invention.
Embodiment 1
Contain 12.5mg Licopyrinobuters for every part in the present embodiment, be listed below in 40 parts of Licopyrinobuter dried emulsifiers main ingredient with it is each
Supplementary product consumption.
Formula：
Preparation method
1. Licopyrinobuter raw material is added in midchain oil, stirring and dissolving；
2. hypromellose (E5) is added in 100ml water, stirring and dissolving, sucrose stirring and dissolving is added in, is added in poly-
Ethylene glycol 400, Tween-80 stir evenly；
3. solution 1 and solution 2 are mixed 20000rpm to stir 3 minutes, then recycled 6 times by high pressure homogenizer 1000bar,
Lotion is made；
4. gained emulsion spray is dried, powdered dry breast is obtained；Orange essence, Aspartame, magnesium stearate is added in mix
It closes uniformly, dispenses to obtain dried emulsifier.
Dried emulsifier emulsion is tested
The dried emulsifier 1g of the embodiment of the present invention 1 is taken, is put into 100ml distilled water, glass bar stirring can obtain emulsion.
Embodiment 2
Contain 25mg Licopyrinobuters for every part in the present embodiment, be listed below in 40 parts of Licopyrinobuter dried emulsifiers main ingredient with it is each auxiliary
Expect dosage.
Formula：
Preparation method
1. Licopyrinobuter raw material is added in midchain oil, stirring and dissolving；
2. hypromellose (E5) is added in 100ml water, stirring and dissolving, sucrose stirring and dissolving is added in, is added in poly-
Ethylene glycol 400, Tween-80 stir evenly；
3. solution 1 and solution 2 are mixed 16000rpm to stir 3 minutes, then recycled 6 times by high pressure homogenizer 1000bar,
Lotion is made；
4. gained lotion rotary evaporation is dried, soft blocky dry breast is obtained, light repoussage reason adds in orange essence, A Siba
Sweet tea, magnesium stearate are uniformly mixed, and dispense to obtain dried emulsifier.
Dried emulsifier emulsion is tested
The powder 1g of the embodiment of the present invention 2 is taken, is put into 100ml distilled water, glass bar stirring can obtain emulsion.
Embodiment 3
Contain 50mg Licopyrinobuters for every part in the present embodiment, be listed below in 40 parts of Licopyrinobuter dried emulsifiers main ingredient with it is each auxiliary
Expect dosage.
Formula：
Preparation method
1. Licopyrinobuter raw material is added in midchain oil, stirring and dissolving；
2. hypromellose (E5) is added in 100ml water, stirring and dissolving, sucrose stirring and dissolving is added in, is added in poly-
Ethylene glycol 400, Tween-80 stir evenly；
3. solution 1 and solution 2 are mixed 20000rpm to stir 3 minutes, lotion is made；
4. gained lotion rotary evaporation is dried, soft blocky dry breast is obtained, light repoussage reason adds in orange essence, A Siba
Sweet tea, magnesium stearate are uniformly mixed, and dispense to obtain dried emulsifier.
Dried emulsifier emulsion is tested
The powder 1.4g of the embodiment of the present invention 3 is taken, is put into 100ml distilled water, glass bar stirring can obtain emulsion.
Embodiment 4
Contain 12.5mg Licopyrinobuters for every part in the present embodiment, be listed below in 40 parts of Licopyrinobuter dried emulsifiers main ingredient with it is each
Supplementary product consumption.
Formula
Preparation method
1. Licopyrinobuter raw material is added in tea oil, stirring and dissolving；
2. hypromellose (E5) is added in 100ml water, stirring and dissolving, sucrose stirring and dissolving is added in, is added in poly-
Ethylene glycol 400, Tween-80 stir evenly；
3. solution 1 and solution 2 are mixed 18000rpm to stir 3 minutes, lotion is made；
4. gained lotion rotary evaporation is dried, soft blocky dry breast is obtained, light repoussage reason adds in grape essence, acetyl ammonia
Base potassium sulfonate, Aspartame, superfine silica gel powder are uniformly mixed, and dispense to obtain dried emulsifier.
Dried emulsifier emulsion is tested
The powder 1g of the embodiment of the present invention 4 is taken, is put into 100ml distilled water, glass bar stirring can obtain emulsion.
Embodiment 5
Contain 25mg Licopyrinobuters for every part in the present embodiment, be listed below in 40 parts of Licopyrinobuter dried emulsifiers main ingredient with it is each auxiliary
Expect dosage.
Formula
Preparation method
1. Licopyrinobuter raw material is added in tea oil, stirring and dissolving；
2. hypromellose (E5) is added in 100ml water, stirring and dissolving, sucrose stirring and dissolving is added in, is added in poly-
Ethylene glycol 400, Tween-80 stir evenly；
3. solution 1 and solution 2 are mixed 2400rpm to stir 10 minutes, lotion is made；
4. gained lotion rotary evaporation is dried, soft blocky dry breast is obtained, light repoussage reason adds in grape essence, acetyl ammonia
Base potassium sulfonate, Aspartame, superfine silica gel powder are uniformly mixed, and dispense to obtain dried emulsifier.
Dried emulsifier emulsion is tested
The powder 1g of the embodiment of the present invention 5 is taken, is put into 100ml distilled water, glass bar stirring can obtain emulsion.
Embodiment 6
Contain 50mg Licopyrinobuters for every part in the present embodiment, be listed below in 40 parts of Licopyrinobuter dried emulsifiers main ingredient with it is each auxiliary
Expect dosage.
Formula
Preparation method
1. Licopyrinobuter raw material is added in tea oil, stirring and dissolving；
2. hypromellose (E5) is added in 100ml water, stirring and dissolving, sucrose stirring and dissolving is added in, is added in poly-
Ethylene glycol 400, Tween-80 stir evenly；
3. solution 1 and solution 2 are mixed 15000rpm to stir 3 minutes, then recycled 6 times by high pressure homogenizer 1000bar,
Lotion is made；
4. gained emulsion spray is dried, obtain powder and do breast；Add in grape essence, acesulfame potassium, A Siba
Sweet tea, superfine silica gel powder are uniformly mixed, and dispense to obtain dried emulsifier.
Dried emulsifier emulsion is tested
The powder 1.4g of the embodiment of the present invention 6 is taken, is put into 100ml distilled water, glass bar stirring can obtain emulsion.
Embodiment 7
Contain 12.5mg Licopyrinobuters for every part in the present embodiment, be listed below in 40 parts of Licopyrinobuter dried emulsifiers main ingredient with it is each
Supplementary product consumption.
Formula
Preparation method
1. Licopyrinobuter raw material is added in midchain oil, stirring and dissolving；
2. PVP K30 is added in 100ml water, stirring and dissolving, lactose stirring and dissolving is added in, adds in poly- second
Glycol 400, Tween-80 stir evenly；
3. solution 1 and solution 2 are mixed 15000rpm to stir 3 minutes, then recycled 6 times by high pressure homogenizer 1000bar,
Lotion is made；
4. gained emulsion spray is dried, obtain powder and do breast；Add in orange essence, Aspartame, magnesium stearate mixing
Uniformly, dried emulsifier is dispensed to obtain.
Dried emulsifier emulsion is tested
The powder 1.4g of the embodiment of the present invention 7 is taken, is put into 100ml distilled water, glass bar stirring can obtain emulsion.
Embodiment 8
Contain 25mg Licopyrinobuters for every part in the present embodiment, be listed below in 40 parts of Licopyrinobuter dried emulsifiers main ingredient with it is each auxiliary
Expect dosage.
Formula
Preparation method
1. Licopyrinobuter raw material is added in midchain oil, stirring and dissolving；
2. PVP K30 is added in 100ml water, stirring and dissolving, lactose stirring and dissolving is added in, adds in poly- second
Glycol 400, Tween-80 stir evenly；
3. solution 1 and solution 2 are mixed 15000rpm to stir 3 minutes, then recycled 6 times by high pressure homogenizer 1000bar,
Lotion is made；
4. gained emulsion spray is dried, obtain powder and do breast；Add in orange essence, Aspartame, magnesium stearate mixing
Uniformly, dried emulsifier is dispensed to obtain.
Dried emulsifier emulsion is tested
The powder 1g of the embodiment of the present invention 8 is taken, is put into 100ml distilled water, glass bar stirring can obtain emulsion.
Embodiment 9
Contain 50mg Licopyrinobuters for every part in the present embodiment, be listed below in 40 parts of Licopyrinobuter dried emulsifiers main ingredient with it is each auxiliary
Expect dosage.
Formula
Preparation method
1. Licopyrinobuter raw material is added in midchain oil, stirring and dissolving；
2. PVP K30 is added in 100ml water, stirring and dissolving, lactose stirring and dissolving is added in, adds in poly- second
Glycol 400, Tween-80 stir evenly；
3. solution 1 and solution 2 are mixed 20000rpm to stir 3 minutes, then recycled 6 times by high pressure homogenizer 1000bar,
Lotion is made；
4. gained emulsion spray is dried, obtain powder and do breast；Add in grape essence, Aspartame, acetamide sulfonic
Potassium, superfine silica gel powder are uniformly mixed, and dispense to obtain dried emulsifier.
Dried emulsifier emulsion is tested
The powder 1.4g of the embodiment of the present invention 9 is taken, is put into 100ml distilled water, glass bar stirring can obtain emulsion.
Embodiment 10
Contain 12.5mg Licopyrinobuters for every part in the present embodiment, be listed below in 40 parts of Licopyrinobuter dried emulsifiers main ingredient with it is each
Supplementary product consumption.
Formula
Preparation method
1. Licopyrinobuter raw material is added in tea oil, stirring and dissolving；
2. PVP K30 is added in 100ml water, stirring and dissolving, lactose stirring and dissolving is added in, adds in poly- second
Glycol 400, Tween-80 stir evenly；
3. solution 1 and solution 2 are mixed 2400rpm to stir 10 minutes, lotion is made；
4. gained lotion rotary evaporation is dried, soft blocky dry breast is obtained, light repoussage reason adds in grape essence, A Siba
Sweet tea, acesulfame potassium, superfine silica gel powder are uniformly mixed, and dispense to obtain dried emulsifier.
Dried emulsifier emulsion is tested
The powder 1g of the embodiment of the present invention 10 is taken, is put into 100ml distilled water, glass bar stirring can obtain emulsion.
Embodiment 11
Contain 25mg Licopyrinobuters for every part in the present embodiment, be listed below in 40 parts of Licopyrinobuter dried emulsifiers main ingredient with it is each auxiliary
Expect dosage.
Formula
Preparation method
1. Licopyrinobuter raw material is added in tea oil, stirring and dissolving；
2. PVP K30 is added in 100ml water, stirring and dissolving, lactose stirring and dissolving is added in, adds in poly- second
Glycol 400, Tween-80 stir evenly；
3. solution 1 and solution 2 are mixed 18000rpm to stir 3 minutes, then recycled 6 times by high pressure homogenizer 1000bar,
Lotion is made；
4. gained emulsion spray is dried, obtain powder and do breast, add in grape essence, Aspartame, acetamide sulfonic
Potassium, superfine silica gel powder are uniformly mixed, and dispense to obtain dried emulsifier.
Dried emulsifier emulsion is tested
The powder 1g of the embodiment of the present invention 11 is taken, is put into 100ml distilled water, glass bar stirring can obtain emulsion.
Embodiment 12
Contain 50mg Licopyrinobuters for every part in the present embodiment, be listed below in 40 parts of Licopyrinobuter dried emulsifiers main ingredient with it is each auxiliary
Expect dosage.
Formula
Preparation method
1. Licopyrinobuter raw material is added in tea oil, stirring and dissolving；
2. PVP K30 is added in 100ml water, stirring and dissolving, lactose stirring and dissolving is added in, adds in poly- second
Glycol 400, Tween-80 stir evenly；
3. solution 1 and solution 2 are mixed 18000rpm to stir 3 minutes, then recycled 6 times by high pressure homogenizer 1000bar,
Lotion is made；
4. gained emulsion spray is dried, obtain powder and do breast, add in grape essence, Aspartame, acetamide sulfonic
Potassium, superfine silica gel powder are uniformly mixed, and dispense to obtain dried emulsifier.
Dried emulsifier emulsion is tested
The powder 1.4g of the embodiment of the present invention 12 is taken, is put into 100ml distilled water, glass bar stirring can obtain emulsus
Liquid.
Claims (20)
1. a kind of Licopyrinobuter dried emulsifier, which is characterized in that the dried emulsifier include Licopyrinobuter as active component, oil,
Emulsifier, water-soluble polymer, filler, corrigent；The weight ratio of wherein described Licopyrinobuter and oil is 1：8 to 1：200；Institute
State emulsifier weight is the weight of oil 4% to 30%.
2. Licopyrinobuter dried emulsifier according to claim 1, after being redissolved with water, the emulsion droplet arithmetic average of gained emulsion
Diameter is less than 5000nm.
3. Licopyrinobuter dried emulsifier according to claim 2, after being redissolved with water, the emulsion droplet arithmetic average of gained emulsion
Diameter is 1000~3000nm.
4. Licopyrinobuter dried emulsifier according to claim 2, after being redissolved with water, the emulsion droplet arithmetic average of gained emulsion
Diameter is 800~2000nm.
5. according to claim 1-4 any one of them Licopyrinobuter dried emulsifiers, the oil is selected from following one or more
Combination：Midchain oil, soybean oil, safflower oil, tea oil, olive oil, peanut oil, sesame oil, coconut oil and corn oil；Wherein described profit
Can Rui Te with oil weight ratio be 1：8 to 1：150.
6. the weight ratio of Licopyrinobuter dried emulsifier according to claim 5, the Licopyrinobuter and oil is 1：8 to 1：100.
7. Licopyrinobuter dried emulsifier according to claim 5, the oil is midchain oil；Wherein described Licopyrinobuter and oil
Weight ratio be 1：8 to 1：50.
8. according to the Licopyrinobuter dried emulsifier of claims 1 or 2, wherein the emulsifier is selected from following one or more groups
It closes：Polyethylene glycol, Tween-80, lecithin, cephalin and soybean lecithin；Wherein described emulsifier weight is the oil weight
The 5% to 30% of amount.
9. according to the Licopyrinobuter dried emulsifier of claims 1 or 2, wherein the emulsifier is Tween-80；It is wherein described
Emulsifier weight is the 5% to 20% of the weight of oil.
10. Licopyrinobuter dried emulsifier according to claim 9, wherein the emulsifier weight be the weight of oil 6% to
15%.
11. according to the Licopyrinobuter dried emulsifier of claims 1 or 2, wherein the water-soluble polymer be selected from it is following a kind of or
Several combinations：Polyvinylpyrrolidone, hydroxypropyl methyl cellulose, hydroxypropyl cellulose, polyethylene glycol, water-soluble polypropylene acid
Copolymer, polyvinyl alcohol；Wherein described water-soluble polymer weight is the 5% to 50% of dried emulsifier total weight.
12. Licopyrinobuter dried emulsifier according to claim 11, wherein the water-soluble polymer is polyvinylpyrrolidone,
Hydroxypropyl methyl cellulose, polyethylene glycol or its mixture；Wherein described water-soluble polymer weight is dried emulsifier total weight
10% to 40%.
13. Licopyrinobuter dried emulsifier according to claim 12, wherein the water-soluble polymer is hydroxypropyl methyl fiber
Element；Wherein described water-soluble polymer weight is the 10% to 30% of dried emulsifier total weight.
14. according to the Licopyrinobuter dried emulsifier of claims 1 or 2, wherein the filler is selected from following one or two kinds of groups
It closes：White granulated sugar, sucrose, mannitol, sorbierite, xylitol, trehalose, maltitol, galactitol, inositol, dextrin, ring paste
Essence；Wherein described filler weight is the 20% to 50% of dried emulsifier total weight.
15. Licopyrinobuter dried emulsifier according to claim 14, wherein the filler is selected from lactose, mannitol, sucrose；Its
Described in filler weight be dried emulsifier total weight 25% to 40%.
16. Licopyrinobuter dried emulsifier according to claim 1 or 2, wherein the Licopyrinobuter is dried emulsifier total weight
0.01% to 10%.
17. Licopyrinobuter dried emulsifier according to claim 16, wherein the Licopyrinobuter is dried emulsifier total weight
0.05% to 8%.
18. Licopyrinobuter dried emulsifier according to claim 16, wherein the Licopyrinobuter is dried emulsifier total weight 0.1%
To 5%.
19. the preparation method of the Licopyrinobuter dried emulsifier described in claims 1 or 2, which is characterized in that including by each component in water
In the step of being prepared into the prewired lotion of oil-in-water type and the step of the water in the prewired lotion is removed.
20. the preparation method of Licopyrinobuter dried emulsifier according to claim 19, which is characterized in that remove the dry powder after water
It is dispensed after adding in corrigent, orally available dried emulsifier is made.
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| FR3102356B1 (en) * | 2019-10-28 | 2021-09-17 | Mohamed Skiba | PHARMACEUTICAL COMPOSITION INCLUDING MITOTANE FOR ORAL ADMINISTRATION FOR THE TREATMENT OF CORTICOSURRENAL CARCINOMA AND CUSHING SYNDROME |
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