CN105055314A - Abiraterone oral spray and use and preparation methods thereof - Google Patents
Abiraterone oral spray and use and preparation methods thereof Download PDFInfo
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Abstract
The invention relates to the technical field of pharmaceutical preparations and particularly relates to an abiraterone oral spray. The abiraterone oral spray comprises the following components in percent by weight: abiraterone acetate, an oil phase, a surfactant, a co-surfactant and the balance of water, wherein the oil phase is used as a carrier for prompting system micro-emulsification, and the oil phase is medium chain triglyceride, ethyl oleate or oleic acid; the surfactant is used for improving the performance of the abiraterone oral spray, expanding the range of application and realizing solubilization, and the surfactant is polyoxyethylene 40 hydrogenated castor oil or polyoxyethylene 35 castor oil; and the co-surfactant is used for reducing the surface tension of liquid and enhancing the emulsifying, moistening and blistering effects, and the co-surfactant is ethanol, n-butyl alcohol or propylene glycol. The spray has the advantages that the taking dose is reduced, so that the manufacturing cost is lowered; the formation of invalid metabolites is reduced, so that adverse reactions are effectively reduced; and the drug effect of the spray is longer than that of an oral drug.
Description
Technical field
The present invention relates to technical field of medicine, be specifically related to a kind of oral spray of abiraterone.
Background technology
Abiraterone acetate, also known as making Abiraterone acetate ester, abiraterone acetas, English Abirateroneacetate by name, chemistry is by name: (3beta)-17-(3-pyridine radicals)-androstane-5,16-diene-3-acetas, English language Chemical is called 17-(3-pyridyl)-5,16-androstadien-3beta-acetate or (3beta)-17-(3-pyridinyl)-Androsta-5,16-dien-3-olacetate (ester); Its chemical constitution is as follows:
Abiraterone acetate is that a kind of white is to pale, nonhygroscopic crystalline powder.Its molecular formula is C
26h
33nO
2, molecular weight 391.55.Abiraterone acetate is a kind of lipophilic compound, and octanol-water partition coefficient is 5.12 (LogP), water insoluble especially.
Abiraterone acetate (abirateroneacetate) is the precursor medicine of abiraterone, be converted into abiraterone rapidly in vivo, the latter is CYP17(17 α-hydroxylase and C17,20-lyases) selectivity, irreversible steroid inhibitor, stop the testosterone synthesis in testis, adrenal gland and tumor by inhibitory enzyme activity.This product is held by Johnson Co., U.S. FDA listing approval is obtained first on April 28th, 2011, for the castration-resistant metastatic prostate cancer (mCRPC) with prednisone or prednisolone therapeutic alliance androgen ablation therapy and docetaxel chemotherapy failure patient, indication crowd is expanded, for the treatment of castration-resistant advanced metastatic carcinoma of prostate again afterwards in December in 2012 approval on the 10th.Because Abiraterone acetate belongs to endocrine therapy, can suppress the androgen that testis and other positions of health produce, therefore relative to current conventional therapy, it has better curative effect, lower side effect, has started the frontier of anti-androgen therapy simultaneously.
Although Abiraterone acetate oral medication advanced prostate cancer is respond well, the taking dose of its oral tablet is large, and bioavailability is low, and large by the impact of food, and untoward reaction is many.
Abiraterone acetate oral tablet (ZYTIGA) commercially available at present, every day, 1 1000mg, as the absorption increasing medicine taken by this medicine together with food, thus likely caused the exposure and the Level Change drug exposure that increase medicine; Therefore answer this medicine of (medicine) being taken before meal, at least within two hours, this medicine should be taken one hour ante cibum or at least after the meal.This medicine and human plasma protein fraction, albumin and α-1 acidoglycoprotein height combine (>99%), inactive form is metabolized to by CYP3A4 and SULT2A1, two major circulating metabolites are sulphuric acid abiraterone (non-activity) and nitrogen oxidation sulphuric acid abiraterone (non-activity), respectively account for about 43% of exposure.
Summary of the invention
The object of the invention is to solve current Abiraterone acetate medicament Problems existing, the taking dose as oral tablet is large, bioavailability is low and large by the impact of food, untoward reaction is many, provides a kind of oral spray of abiraterone.
Meanwhile, the oral spray of Abiraterone acetate of the present invention also solves because the water insoluble of Abiraterone acetate and its unique properties cause it not easily to form the problem of microemulsion from formula.
In addition, present invention provides a kind of preparation method of oral spray of abiraterone, by adopting this preparation method, and in conjunction with formula of the present invention, the good spray of microemulsion effect can be prepared.
Abiraterone acetate and a certain amount of MCT Oil, ethanol, polyoxyethylene hydrogenated Oleum Ricini EL35 and water are made the aqueous solution of microemulsion by the present invention, and with sucrose and Fructus Musae powder for correctives, finally make the spray with quantitative valve.This aerosol spray, in Sublingual, makes Abiraterone acetate be absorbed by sublingual mucosa, can avoid the first-selected effect of liver, significantly improve bioavailability, reduce toxic and side effects occurrence risk.
In order to reach foregoing invention object, the present invention by the following technical solutions:
An oral spray for abiraterone, by weight percentage, comprises following component, abiraterone acetas 0.44-2.17%; Oil phase 5.01-9.05%; Cosurfactant 4.42-5.46%; Surfactant 11.07-19.18%; Water surplus.
Oil phase, as carrier, impels system microemulsified; Surfactant effectively reduces surface tension of liquid, strengthens the effects such as emulsifying, moistening, foaming; Cosurfactant can reduce costs, and improves performance and the scope of application of surfactant, realizes solubilization.Not soluble in water due to Abiraterone acetate, and the character of himself uniqueness causes its microemulsified difficulty, therefore difficult point of the present invention is to design the proportioning being easy to form microemulsion.
Described oil phase is median chain triglyceride oil, ethyl oleate or oleic acid.Because the logP value of abiraterone acetas is not soluted in water for 5.1(pole), so adopt the low oil phase of HLB value to dissolve, such as oleic acid, ethyl oleate and miglyol 812.
Described surfactant is polyoxyl 40 hydrogenated castor oil or CREMOPHORE EL.
Described cosurfactant is ethanol, n-butyl alcohol or propylene glycol.
Preferably, by weight percentage, correctives 2.65-3.27% is also comprised.
Preferably, described correctives is sucrose and Fructus Musae powder; The weight percent content of described sucrose is 1.77-2.18%; The weight percent content of Fructus Musae powder is 0.88-1.09%.
Preferably, by weight percentage, antibacterial potassium sorbate 0.14-0.19% is also comprised.
Preferably, by weight percentage, described abiraterone acetas is 3/50 of oil phase; Described cosurfactant is 1/3 of surfactant.
Preferably, each dosage is 2-5mg.
A preparation method for the oral spray of abiraterone, specifically comprises the following steps:
(1) take the oil phase of formula ratio respectively, cosurfactant, surfactant mixes and stirs;
(2) the abiraterone acetas taking formula ratio again stirs in wherein, under being then placed on the water bath condition of 40-50 DEG C;
(3) mixed liquor of step (2) is stirred 30 minutes with the rotating speed of 210rpm, form microemulsion;
(4) by the microemulsion natural cooling of step (3), filter also fill in the spray bottle with quantitative valve, the oral spray of obtained Abiraterone acetate, the temperature of natural cooling is 15-20 DEG C, and product is carried out constant temperature preservation in this temperature range.
Preferably, step (3) first by the correctives of formula ratio and potassium sorbate soluble in water and filter, then adopt dropping mode this aqueous solution is joined step (2) mixed liquor in, and to stir with the rotating speed of 350rpm, until aqueous solution all dropwises simultaneously.Time for adding is 5-15 minute.
Compared with prior art, beneficial effect is in the present invention:
The general efficiency of sublingual absorption can reach more than 80%.Because absorption efficiency is higher, on this basis, drug dose design can be more accurate, and finally, this product significantly reduces taking dose after changing sublingual absorption into, thus reduces manufacturing cost.
The abiraterone acetas gone on the market at present is that oral tablet (taking dose is 1000mg/ time) finds that there is 86% for invalid metabolite after gastrointestinal tract absorbs, the untoward reaction of peroral dosage form is very likely that it produces, the formation of invalid metabolite can be reduced after changing sublingual absorption into, thus effectively reduce untoward reaction.
Having in dosage 1000mg every day in transfer CRPC patient, Cmax steady-state value (mean ± SD) is 226 ± 178ng/mL and AUC is 993 ± 639ng.hr/mL.
Therefore, in order to reduce taking dose, improve bioavailability, Abiraterone acetate is made the micro-emulsion type spray with quantitative valve by the present inventor.Simultaneously, the clinical testing data AUC of above-mentioned commercially available Abiraterone acetate oral tablet (ZYTIGA) is utilized to be 993 ± 639ng.hr/mL and this medicine and human plasma protein fraction, albumin and α-1 acidoglycoprotein height combine (>99%), this medicine known is mainly distributed in blood, pass through formula: dosage (X0)=AUC × blood of human body volume (3.0L), can be calculated taking dose of the present invention and be approximately 3 ± 0.5mg.Therefore inventor tentatively determines that dosage scope of the present invention is 2-5mg, preferred 3mg.
Because sublingual absorption is soon more oral, thus blood medicine reach peak (Tmax) also can be short, but about 12 hours blood medicine half-life of abiraterone, drug effect is than oral length.
Detailed description of the invention
Below by specific embodiment, explanation is further described to technical scheme of the present invention.
If without specified otherwise, the raw material adopted in embodiments of the invention is the conventional raw material in this area, and the method adopted in embodiment, is the conventional method of this area.
The total amount of following embodiment is all in 100g, and the actual time that this spray is applied to, in spray bottle, the quantitative value of charge weight and quantitative valve is determined according to the Dose standard above through calculating, the taking dose obtaining spray of the present invention above as calculated is afterwards 3 ± 0.5mg, therefore inventor tentatively determines that dosage scope of the present invention is 2-5mg, preferred 3mg.Therefore, when designing spray bottle, combine actual to its each spray amount and often bottledly enter two to carry out specializing and design.
embodiment 1:
An oral spray for abiraterone, by weight percentage, comprises following component, abiraterone acetas 0.44%; Oil phase (median chain triglyceride oil, ethyl oleate or oleic acid) 9.05%; Cosurfactant (ethanol, n-butyl alcohol or propylene glycol) 4.42%; Surfactant (polyoxyl 40 hydrogenated castor oil or CREMOPHORE EL) 19.18%; Water surplus.
A preparation method for the oral spray of abiraterone, specifically comprises the following steps:
(1) take the oil phase of formula ratio respectively, cosurfactant, surfactant mixes and stirs;
(2) the abiraterone acetas taking formula ratio again stirs in wherein, under being then placed on the water bath condition of 40-50 DEG C;
(3) mixed liquor of step (2) is stirred 30 minutes with the rotating speed of 210rpm, form microemulsion;
(4) by the microemulsion natural cooling of step (3), filter also fill in the spray bottle with quantitative valve, the oral spray of obtained Abiraterone acetate, the temperature of natural cooling is 15-20 DEG C, and product is carried out constant temperature preservation in this temperature range.
embodiment 2:
An oral spray for abiraterone, by weight percentage, comprises following component, abiraterone acetas 2.17%; Oil phase (median chain triglyceride oil, ethyl oleate or oleic acid) 5.01%; Cosurfactant (ethanol, n-butyl alcohol or propylene glycol) 5.46%; Surfactant (polyoxyl 40 hydrogenated castor oil or CREMOPHORE EL) 11.07%; Water surplus.
A preparation method for the oral spray of abiraterone, specifically comprises the following steps:
(1) take the oil phase of formula ratio respectively, cosurfactant, surfactant mixes and stirs;
(2) the abiraterone acetas taking formula ratio again stirs in wherein, under being then placed on the water bath condition of 40-50 DEG C;
(3) mixed liquor of step (2) is stirred 30 minutes with the rotating speed of 210rpm, form microemulsion;
(4) by the microemulsion natural cooling of step (3), filter also fill in the spray bottle with quantitative valve, the oral spray of obtained Abiraterone acetate, the temperature of natural cooling is 15-20 DEG C, and product is carried out constant temperature preservation in this temperature range.
embodiment 3:
An oral spray for abiraterone, by weight percentage, comprises following component, abiraterone acetas 0.51%; Abiraterone acetas is 3/50 of oil phase, and oil phase (median chain triglyceride oil, ethyl oleate or oleic acid) is specially 8.5%; Cosurfactant (ethanol, n-butyl alcohol or propylene glycol) cosurfactant is 1/3 of surfactant, is specially 4.56%; Surfactant (polyoxyl 40 hydrogenated castor oil or CREMOPHORE EL) 13.68%; Correctives 2.65%(sucrose 1.77%, Fructus Musae powder 0.88%); Antibacterial potassium sorbate 0.19%; Water surplus.
A preparation method for the oral spray of abiraterone, specifically comprises the following steps:
(1) take the oil phase of formula ratio respectively, cosurfactant, surfactant mixes and stirs;
(2) the abiraterone acetas taking formula ratio again stirs in wherein, under being then placed on the water bath condition of 40-50 DEG C;
(3) first by the correctives of formula ratio and potassium sorbate soluble in water and filter, then adopt dropping mode this aqueous solution is joined step (2) mixed liquor in, and to stir with the rotating speed of 350rpm, until aqueous solution all dropwises simultaneously; Then stir 30 minutes with the rotating speed of 210rpm, form microemulsion;
(4) by the microemulsion natural cooling of step (3), filter also fill in the spray bottle with quantitative valve, the oral spray of obtained Abiraterone acetate, the temperature of natural cooling is 15-20 DEG C, and product is carried out constant temperature preservation in this temperature range.
embodiment 4:
An oral spray for abiraterone, by weight percentage, comprises following component, abiraterone acetas 0.47%; Oil phase (median chain triglyceride oil, ethyl oleate or oleic acid) 5.95%; Cosurfactant (ethanol, n-butyl alcohol or propylene glycol) 4.86%; Surfactant (polyoxyl 40 hydrogenated castor oil or CREMOPHORE EL) 15.18%; Correctives 3.27%(sucrose 2.18%, Fructus Musae powder 1.09%); Antibacterial potassium sorbate 0.14%; Water surplus.
A preparation method for the oral spray of abiraterone, specifically comprises the following steps:
(1) take the oil phase of formula ratio respectively, cosurfactant, surfactant mixes and stirs;
(2) the abiraterone acetas taking formula ratio again stirs in wherein, under being then placed on the water bath condition of 40-50 DEG C;
(3) first by the correctives of formula ratio and potassium sorbate soluble in water and filter, then adopt dropping mode this aqueous solution is joined step (2) mixed liquor in, and to stir with the rotating speed of 350rpm, until aqueous solution all dropwises simultaneously; Then stir 30 minutes with the rotating speed of 210rpm, form microemulsion;
(4) by the microemulsion natural cooling of step (3), filter also fill in the spray bottle with quantitative valve, the oral spray of obtained Abiraterone acetate, the temperature of natural cooling is 15-20 DEG C, and product is carried out constant temperature preservation in this temperature range.
embodiment 5:
An oral spray for abiraterone, by weight percentage, comprises following component, abiraterone acetas 1.87%; Oil phase (median chain triglyceride oil) 7.78%; Cosurfactant (ethanol) 4.67%; Surfactant (polyoxyl 40 hydrogenated castor oil) 17.42%; Correctives (sucrose 1.87%, Fructus Musae powder 0.93%); Antibacterial potassium sorbate 0.16%.Water surplus.
A preparation method for the oral spray of abiraterone, specifically comprises the following steps:
(1) take the oil phase of formula ratio respectively, cosurfactant, surfactant mixes and stirs;
(2) the abiraterone acetas taking formula ratio again stirs in wherein, under being then placed on the water bath condition of 40-50 DEG C;
(3) first by the correctives of formula ratio and potassium sorbate soluble in water and filter, then adopt dropping mode this aqueous solution is joined step (2) mixed liquor in, and to stir with the rotating speed of 350rpm, until aqueous solution all dropwises simultaneously; Then stir 30 minutes with the rotating speed of 210rpm, form microemulsion;
(4) by the microemulsion natural cooling of step (3), filter also fill in the spray bottle with quantitative valve, the oral spray of obtained Abiraterone acetate, the temperature of natural cooling is 15-20 DEG C, and product is carried out constant temperature preservation in this temperature range.
embodiment 6:
An oral spray for abiraterone, by weight percentage, comprises following component, abiraterone acetas 1.96%; Oil phase (ethyl oleate) 5.56%; Cosurfactant (ethanol) 4.90%; Surfactant (polyoxyl 40 hydrogenated castor oil) 12.58%; Correctives (sucrose 1.96%, Fructus Musae powder 0.98%); Antibacterial potassium sorbate 0.16%; Water surplus.
A preparation method for the oral spray of abiraterone, specifically comprises the following steps:
(1) take the oil phase of formula ratio respectively, cosurfactant, surfactant mixes and stirs;
(2) the abiraterone acetas taking formula ratio again stirs in wherein, under being then placed on the water bath condition of 40-50 DEG C;
(3) first by the correctives of formula ratio and potassium sorbate soluble in water and filter, then adopt dropping mode this aqueous solution is joined step (2) mixed liquor in, and to stir with the rotating speed of 350rpm, until aqueous solution all dropwises simultaneously; Then stir 30 minutes with the rotating speed of 210rpm, form microemulsion;
(4) by the microemulsion natural cooling of step (3), filter also fill in the spray bottle with quantitative valve, the oral spray of obtained Abiraterone acetate, the temperature of natural cooling is 15-20 DEG C, and product is carried out constant temperature preservation in this temperature range.
embodiment 7:
An oral spray for abiraterone, by weight percentage, comprises following component, abiraterone acetas 1.97%; Oil phase (oleic acid) 5.57%; Cosurfactant (ethanol) 4.92%; Surfactant (CREMOPHORE EL) 12.30%; Correctives (sucrose 1.97%, Fructus Musae powder 0.98%); Antibacterial potassium sorbate 0.16%; Water surplus.
A preparation method for the oral spray of abiraterone, specifically comprises the following steps:
(1) take the oil phase of formula ratio respectively, cosurfactant, surfactant mixes and stirs;
(2) the abiraterone acetas taking formula ratio again stirs in wherein, under being then placed on the water bath condition of 40-50 DEG C;
(3) first by the correctives of formula ratio and potassium sorbate soluble in water and filter, then adopt dropping mode this aqueous solution is joined step (2) mixed liquor in, and to stir with the rotating speed of 350rpm, until aqueous solution all dropwises simultaneously; Then stir 30 minutes with the rotating speed of 210rpm, form microemulsion;
(4) by the microemulsion natural cooling of step (3), filter also fill in the spray bottle with quantitative valve, the oral spray of obtained Abiraterone acetate, the temperature of natural cooling is 15-20 DEG C, and product is carried out constant temperature preservation in this temperature range.
embodiment 8:
An oral spray for abiraterone, by weight percentage, comprises following component, abiraterone acetas 0.99%; Oil phase (ethyl oleate) 6.61%; Cosurfactant (ethanol) 4.96%; Surfactant (polyoxyl 40 hydrogenated castor oil) 14.88%; Correctives (sucrose 1.98%, Fructus Musae powder 0.99%); Antibacterial potassium sorbate 0.17%; Water surplus.
A preparation method for the oral spray of abiraterone, specifically comprises the following steps:
(1) take the oil phase of formula ratio respectively, cosurfactant, surfactant mixes and stirs;
(2) the abiraterone acetas taking formula ratio again stirs in wherein, under being then placed on the water bath condition of 40-50 DEG C;
(3) first by the correctives of formula ratio and potassium sorbate soluble in water and filter, then adopt dropping mode this aqueous solution is joined step (2) mixed liquor in, and to stir with the rotating speed of 350rpm, until aqueous solution all dropwises simultaneously; Then stir 30 minutes with the rotating speed of 210rpm, form microemulsion;
(4) by the microemulsion natural cooling of step (3), filter also fill in the spray bottle with quantitative valve, the oral spray of obtained Abiraterone acetate, the temperature of natural cooling is 15-20 DEG C, and product is carried out constant temperature preservation in this temperature range.
embodiment 9:
An oral spray for abiraterone, by weight percentage, comprises following component, abiraterone acetas 2.03%; Oil phase (ethyl oleate) 6.77%; Cosurfactant (n-butyl alcohol) 5.08%; Surfactant (CREMOPHORE EL) 15.23%; Correctives (sucrose 2.03%, Fructus Musae powder 1.02%); Antibacterial potassium sorbate 0.17%; Water surplus.
A preparation method for the oral spray of abiraterone, specifically comprises the following steps:
(1) take the oil phase of formula ratio respectively, cosurfactant, surfactant mixes and stirs;
(2) the abiraterone acetas taking formula ratio again stirs in wherein, under being then placed on the water bath condition of 40-50 DEG C;
(3) first by the correctives of formula ratio and potassium sorbate soluble in water and filter, then adopt dropping mode this aqueous solution is joined step (2) mixed liquor in, and to stir with the rotating speed of 350rpm, until aqueous solution all dropwises simultaneously; Then stir 30 minutes with the rotating speed of 210rpm, form microemulsion;
(4) by the microemulsion natural cooling of step (3), filter also fill in the spray bottle with quantitative valve, the oral spray of obtained Abiraterone acetate, the temperature of natural cooling is 15-20 DEG C, and product is carried out constant temperature preservation in this temperature range.
embodiment 10:
An oral spray for abiraterone, by weight percentage, comprises following component, abiraterone acetas 0.49%; Oil phase (median chain triglyceride oil) 8.22%; Cosurfactant (ethanol) 4.93%; Surfactant (CREMOPHORE EL) 17.43%; Correctives (sucrose 1.97%, Fructus Musae powder 0.99%); Antibacterial potassium sorbate 0.16%; Water surplus.
A preparation method for the oral spray of abiraterone, specifically comprises the following steps:
(1) take the oil phase of formula ratio respectively, cosurfactant, surfactant mixes and stirs;
(2) the abiraterone acetas taking formula ratio again stirs in wherein, under being then placed on the water bath condition of 40-50 DEG C;
(3) first by the correctives of formula ratio and potassium sorbate soluble in water and filter, then adopt dropping mode this aqueous solution is joined step (2) mixed liquor in, and to stir with the rotating speed of 350rpm, until aqueous solution all dropwises simultaneously; Then stir 30 minutes with the rotating speed of 210rpm, form microemulsion;
(4) by the microemulsion natural cooling of step (3), filter also fill in the spray bottle with quantitative valve, the oral spray of obtained Abiraterone acetate, the temperature of natural cooling is 15-20 DEG C, and product is carried out constant temperature preservation in this temperature range.
About the ratio of abiraterone acetas/oil phase and the impurity on the same day as following table: (with embodiment 7,8 and 9 for target)
| Embodiment | Abiraterone acetas/oil phase ratio | Total impurities on the same day (%) |
| Embodiment 7 | 0.35 | 1.1 |
| Embodiment 8 | 0.15 | 1.29 |
| Embodiment 9 | 0.06 | 0.18 |
Although abiraterone acetas is large at the dissolubility of oleic acid and ethyl oleate as can be seen from the above table, the impurity produced is many, therefore selects miglyol 812 (median chain triglyceride oil) better.
According to weight, the dissolubility of abiraterone acetas in miglyol 812 is characterized, sees the following form:
| Abiraterone acetas | Miglyol 812 | Dehydrated alcohol | After ethanol volatilization, whether ABT crystallization separates out | |
| Proportioning 1 | 1 | 1 | 1 | There is crystallization |
| Proportioning 2 | 1 | 2 | 2 | There is crystallization |
| Proportioning 3 | 1 | 3 | 3 | Nodeless mesh is separated out |
| Proportioning 4 | 1 | 4 | 3 | Nodeless mesh is separated out |
The even nodeless mesh of upper table display proportioning 3,4 is separated out, and represents that abiraterone acetas can be dissolved in miglyol 812 completely.
Be dissolved in the compatibility after miglyol 812 about abiraterone acetas, see the following form:
| Condition | Impurity |
| 14 days, 14 DEG C | 0.31% |
| 14 days, 30 DEG C | 1.13% |
| 10 days, 60 DEG C | 4.91% |
Experimentally can find out that abiraterone acetas is stable at 14 DEG C in MCT.
The stability result of the oral spray of embodiment 10 sees the following form
| Time | Condition | Character | Maximum single impurity % | Total impurities % | Content mg/ml |
| 0 day | / | For transparent, and the liquid of the general light blue A Gena that becomes a shareholder, there is aromatic odor | 0.04 | 0.18 | 5.6 |
| 14 days | 14℃ | For transparent, and the liquid of the general light blue A Gena that becomes a shareholder, there is aromatic odor | 0.05 | 0.21 | 5.8 |
| 30 days | 14℃ | For transparent, and the liquid of the general light blue A Gena that becomes a shareholder, there is aromatic odor | 0.09 | 0.24 | 5.5 |
Below the preferred embodiment of invention is illustrated, but the present invention is not limited to described embodiment, those of ordinary skill in the art also can make all equivalent modification or replacement under the prerequisite without prejudice to the invention spirit, and these equivalent modification or replacement are all included in the application's claim limited range.
Claims (8)
1. an oral spray for abiraterone, is characterized in that, by weight percentage, comprises following component,
Abiraterone acetas;
Oil phase, for as the carrier impelling system microemulsified, described oil phase is median chain triglyceride oil, ethyl oleate or oleic acid;
Surfactant, for reducing surface tension of liquid, strengthen emulsifying, moistening, barbotage, described surfactant is polyoxyl 40 hydrogenated castor oil or CREMOPHORE EL;
Cosurfactant, for improving performance and the scope of application of surfactant, realizes solubilization, and described cosurfactant is ethanol, n-butyl alcohol or propylene glycol;
Water surplus.
2. the oral spray of a kind of abiraterone according to claim 1, is characterized in that, by weight percentage, comprises following component,
Abiraterone acetas 0.44-2.17%;
Oil phase 5.01-9.05%;
Surfactant 11.07-19.18%;
Cosurfactant 4.42-5.46%;
Water surplus.
3. the oral spray of a kind of abiraterone according to claim 2, is characterized in that, by weight percentage, also comprises correctives 2.65-3.27%, and described correctives is sucrose and Fructus Musae powder; The weight percent content of described sucrose is 1.77-2.18%; The weight percent content of Fructus Musae powder is 0.88-1.09%.
4. the oral spray of a kind of abiraterone according to claim 2, is characterized in that, by weight percentage, also comprises antibacterial 0.14-0.19%.
5. the oral spray of a kind of abiraterone according to claim 4, is characterized in that, described antibacterial is potassium sorbate.
6. the oral spray of a kind of abiraterone according to claim 2, is characterized in that, by weight percentage, described abiraterone acetas is 3/50 of oil phase; Described cosurfactant is 1/3 of surfactant.
7. the using method of the oral spray of a kind of abiraterone according to claim 1-6, is characterized in that, each dosage is 2-5mg.
8. the preparation method of the oral spray of a kind of abiraterone according to claim 1-6, is characterized in that, specifically comprise the following steps:
(1) take the oil phase of formula ratio respectively, cosurfactant, surfactant mixes and stirs;
(2) the abiraterone acetas taking formula ratio again stirs in wherein, under being then placed on the water bath condition of 40-50 DEG C;
(3) by formula ratio by correctives and antibacterial soluble in water and filter, and in the mixed liquor adopting dropping mode to be joined by this aqueous solution in step (2), and stir with the rotating speed of 350rpm, until aqueous solution all dropwises, then keep 3 minutes;
(4) mixed liquor of step (3) is stirred 30 minutes with the rotating speed of 210rpm, form microemulsion;
(5) microemulsion of step (4) is naturally cooled to 15-20 DEG C, filter also fill in the spray bottle with quantitative valve, the oral spray of obtained Abiraterone acetate, carries out constant temperature preservation in this temperature range by product.
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| CN106913539A (en) * | 2015-12-25 | 2017-07-04 | 山东新时代药业有限公司 | A kind of Abiraterone acetate sublingual tablets and preparation method thereof |
| CN106913538A (en) * | 2015-12-25 | 2017-07-04 | 山东新时代药业有限公司 | A kind of Abiraterone acetate sublingual tablets and preparation method thereof |
| CN106913537A (en) * | 2015-12-25 | 2017-07-04 | 山东新时代药业有限公司 | A kind of Abiraterone acetate sublingual tablets and preparation method thereof |
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| WO2020151633A1 (en) * | 2019-01-25 | 2020-07-30 | Shenzhen Pharmacin Co., Ltd. | Pharmaceutical compositions |
| CN113456588A (en) * | 2021-07-05 | 2021-10-01 | 沈阳药科大学 | Abiraterone acetate solid self-microemulsion and preparation method thereof |
| CN113750032A (en) * | 2020-06-01 | 2021-12-07 | 成都海博为药业有限公司 | Oral abiraterone medicinal composition and preparation method and application thereof |
| CN114306236A (en) * | 2021-12-15 | 2022-04-12 | 湖南慧泽生物医药科技有限公司 | Self-microemulsion system for loading abiraterone acetate, composition and application |
| EP4197541A1 (en) * | 2021-12-15 | 2023-06-21 | Hunan Huize Biopharma S&T Co., Ltd | Abiraterone acetate-containing composition and application thereof |
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| CN106913537B (en) * | 2015-12-25 | 2021-02-09 | 山东新时代药业有限公司 | Abiraterone acetate sublingual tablet and preparation method thereof |
| CN106913538A (en) * | 2015-12-25 | 2017-07-04 | 山东新时代药业有限公司 | A kind of Abiraterone acetate sublingual tablets and preparation method thereof |
| CN106913537A (en) * | 2015-12-25 | 2017-07-04 | 山东新时代药业有限公司 | A kind of Abiraterone acetate sublingual tablets and preparation method thereof |
| CN106913539A (en) * | 2015-12-25 | 2017-07-04 | 山东新时代药业有限公司 | A kind of Abiraterone acetate sublingual tablets and preparation method thereof |
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| CN114306236A (en) * | 2021-12-15 | 2022-04-12 | 湖南慧泽生物医药科技有限公司 | Self-microemulsion system for loading abiraterone acetate, composition and application |
| WO2023109758A1 (en) * | 2021-12-15 | 2023-06-22 | Hunan Huize Biopharma S&T Co., Ltd | Abiraterone acetate-containing composition and application thereof |
| JP2023088878A (en) * | 2021-12-15 | 2023-06-27 | 湖南慧▲澤▼生物医▲薬▼科技有限公司 | Composition containing abiraterone acetate and use |
| JP7320903B2 (en) | 2021-12-15 | 2023-08-04 | 湖南慧▲澤▼生物医▲薬▼科技有限公司 | Compositions and uses containing abiraterone acetate |
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