CN102106866B - Pharmaceutical composition and preparation method thereof - Google Patents
Pharmaceutical composition and preparation method thereof Download PDFInfo
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- CN102106866B CN102106866B CN 200910252556 CN200910252556A CN102106866B CN 102106866 B CN102106866 B CN 102106866B CN 200910252556 CN200910252556 CN 200910252556 CN 200910252556 A CN200910252556 A CN 200910252556A CN 102106866 B CN102106866 B CN 102106866B
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Abstract
The invention relates to a pharmaceutical composition and a preparation method thereof. Based on a large amount of experimental screening, a prescription composition of a etoposide self (micro) emulsification system (ie, pre-emulsification concentrate) is found, wherein the concentrate is clear, transparent, and unlayered, and has the characteristics of high drug content, low adjuvant toxicity, low adjuvant amount, high emulsification speed, and uniform particle size. The preparation method of the invention provides a better curative effect of etoposide, improves the solubility of etoposide, increases the bioavailability, and improves the stability of etoposide; based on the advantages of high efficiency and low toxicity of the new formulation, the antitumor activity of etoposide is fully exerted and the toxic and side effects are reduced, which can undoubtedly promote the clinical applications of etoposide.
Description
Technical field
The present invention relates to a kind of pharmaceutical composition and preparation method thereof, particularly a kind of etoposide and preparation method thereof.
Background technology
Etoposide is mitotic inhibitor, now has been one of our times various countries antitumor drug commonly used.The molecular weight of etoposide is 588, and the utmost point is not soluble in water, normal saline and other physiological solutions.Not opening the used for intravenous injection etoposide of ampoule can at room temperature stablize 24 months, warded off in normal saline or dextrorotation to have identical stability in the anhydride solution.The chemistry of aqueous solution stability of etoposide is very poor, is subject to the pH value impact.In the solution of pH 1.3 and 10, etoposide is degraded rapidly, and degradation half life is respectively 2.88 and 3.83h; In the aqueous solution of pH 7.30, degradation half life is 27.72 days; Scope at pH5-6.15 is relatively the most stable, and degradation half life was respectively 63 days and 49.5 days.Except etoposide, non-active ingredient comprises in the oral soft capsule: citric acid, Tween 80, polyvinyl alcohol 400, ethanol, pure water.
The dosage form that etoposide is commonly used clinically is injection and oral soft capsule, and dosage is every 50-100mg and every 50-100mg.The dosage of vascular drug delivery is every 3-5 days 300-600mg/m
2(being equivalent to body weight is the adult 450-900mg of 70kg).At present, the injection that uses clinically belongs to the non-aqueous solution system, during intravenously administrable, generally dilute with normal saline or G/W first, but unstable, can in infusion process, form fine precipitation, injection blood vessel place causes stronger local excitation, and produces phlebitis.The application of oral formulations is limited to non-critical patient, and its absolute bioavailability is low, only has 45%, and individual variation very large (bioavailability 25%-75%).Etoposide blood drug level persistent period length is just more important than peak concentration.The curative effect of bibliographical information etoposide has the obvious course for the treatment of (being the time) dependency.Same dosage divides administration in many days than 1 time or 1 administration curative effect is higher weekly, and bone marrow depression obviously alleviates.The raising of curative effect is relevant with the dense time greater than 1 μ g/ml of blood plasma medicine after the long term administration, and irrelevant with peak plasma concentration or AUC.When plasma concentration during at 1～3 μ g/ml, cellulotoxic effect is better, and bone marrow toxicity is also lighter; When plasma concentration during greater than 5 μ g/ml, antitumous effect increases not obvious. and bone marrow toxicity obviously increases the weight of.Low dosage, long-time continuous administration are described, may improve curative effect, reduce toxicity.
Water-soluble hardly because of etoposide, it is fat-soluble also relatively poor, so existing soft capsule oral preparation bioavailability is low, has seriously restricted the performance of its drug effect.
In document " the prescription research of an etoposide self-microemulsion " literary composition, the author has carried out the development of novel formulation-self-microemulsion for the deficiency of existing soft capsule, obtain prescription take isopropyl myristate, polyoxyethylene hydrogenated Oleum Ricini, PEG400 as adjuvant through screening, this prescription stripping, better stable, the emulsion character that obtains after the emulsifying is better.Solved existing soft capsule causes poor stability because containing ethanol problem.Yet at present, isopropyl myristate can not be used for human body at home, also be mainly used in abroad in cosmetics and a small amount of topical formulations, therefore, and in fact, too not large practical value of this invention.In document " research of an Etoposide Microemulsion phasor " literary composition, also be to have adopted isopropyl myristate, there is same problem; And etoposide stability is very poor, is not suitable for placing for a long time in aqueous environment, therefore the practicality that should invent is worth discussion.
In addition, existing etoposide soft capsule also has that a fairly obvious shortcoming---individual variation is large, bioavailability is low.Therefore, necessary further improvement prior art solves the problem that exists.
Summary of the invention
The object of the invention is to provide a kind of pharmaceutical composition; Another object of the present invention is to provide the preparation method of this pharmaceutical composition.
The present invention seeks to be achieved through the following technical solutions:
The raw material of pharmaceutical composition of the present invention consists of:
Oil phase 0.5-2 weight portion etoposide 0.2-1 weight portion
Emulsifying agent 2-6 weight portion cosolvent 1.5-6 weight portion
PH adjusting agent 0.05-0.15 weight portion.
The raw material composition of pharmaceutical composition of the present invention is preferably:
Emulsifying agent 5 weight portion cosolvents 2.5 weight portions
PH adjusting agent 0.1 weight portion.
The raw material composition of pharmaceutical composition of the present invention is preferably:
Emulsifying agent 3.6 weight portion cosolvents 4.8 weight portions
PH adjusting agent 0.12 weight portion.
The raw material composition of pharmaceutical composition of the present invention is preferably:
Emulsifying agent 4.8 weight portion cosolvents 3.6 weight portions
PH adjusting agent 0.12 weight portion.
The raw material composition of pharmaceutical composition of the present invention is preferably:
Emulsifying agent 2.7 weight portion cosolvents 2.5 weight portions
PH adjusting agent 0.1 weight portion.
The raw material composition of pharmaceutical composition of the present invention is preferably:
Emulsifying agent 3 weight portion cosolvents 5.9 weight portions
PH adjusting agent 0.14 weight portion.
The raw material composition of pharmaceutical composition of the present invention is preferably:
Emulsifying agent 5 weight portion cosolvents 2.5 weight portions
PH adjusting agent 0.1 weight portion.
The raw material composition of pharmaceutical composition of the present invention is preferably:
Oil phase 0.9 weight portion etoposide 0.4 weight portion
Emulsifying agent 5.5 weight portion cosolvents 3 weight portions
PH adjusting agent 0.11 weight portion.
The raw material composition of pharmaceutical composition of the present invention is preferably:
Oil phase 0.8 weight portion etoposide 0.6 weight portion
Emulsifying agent 4 weight portion cosolvents 4.6 weight portions
PH adjusting agent 0.12 weight portion.
The raw material composition of pharmaceutical composition of the present invention is preferably:
Oil phase 0.7 weight portion etoposide 0.6 weight portion
Emulsifying agent 5.5 weight portion cosolvents 3.5 weight portions
PH adjusting agent 0.12 weight portion.
The raw material composition of pharmaceutical composition of the present invention is preferably:
Oil phase 0.7 weight portion etoposide 0.9 weight portion
Emulsifying agent 2.5 weight portion cosolvents 5.5 weight portions
PH adjusting agent 0.14 weight portion.
The raw material composition of pharmaceutical composition of the present invention is preferably:
Oil phase 0.7 weight portion etoposide 0.36 weight portion
Emulsifying agent 5.5 weight portion cosolvents 2 weight portions
PH adjusting agent 0.1 weight portion.
The raw material composition of pharmaceutical composition of the present invention is preferably:
Oil phase 1.3 weight portion etoposides 0.6 weight portion
Emulsifying agent 3 weight portion cosolvents 5 weight portions
PH adjusting agent 0.12 weight portion.
Also add one or more in the following raw material in the pharmaceutical composition of the present invention:
Metal-chelator 0.0001-0.1 weight portion, antioxidant 0.0001-0.2 weight portion.
Wherein, described oil phase is medium chain fatty acid ester, long-chain fat acid glyceride and/or polyethyleneglycol glyceride, and wherein said medium chain fatty acid ester is that the fatty acid carbons chain length is at C
8-C
14The fatty acid ester of scope, as: sad monoglyceride, Sunfat GDC-S, Trivent OCG, capric acid monoglyceride, capric acid diglyceride, tricaprin, sad capric acid monoglyceride, sad capric acid diglyceride and/or Miglyol 812N; Described long-chain fat acid glyceride is one or more in oleic acid sorbitol ester, olein, glyceryl linoleate and the Oleum helianthi glyceride; Described polyethyleneglycol glyceride is one or more in oleoyl polyethyleneglycol glyceride, inferior oleoyl polyethyleneglycol glyceride and the stearoyl polyoxy glyceride.
Described emulsifying agent is polysorbate, polyoxyethylene castor oil and derivant thereof, alpha-tocopherol and/or polyethyleneglycol glyceride; Wherein said polysorbate is that in polysorbate60 (Tween 60) and the polysorbate80 (Tween 80) one or both share; Described polyoxyethylene castor oil and derivant thereof refer to one or more in CREMOPHORE EL and purification level, Emulsifier EL-40 and purification level, polyoxyl 40 hydrogenated castor oil and purification level and Cremophor RH60 and the purification level; Described alpha-tocopherol refers to alpha-tocopherol polyethylene glycol succinate (vitamin E TPGS), alpha-tocopherol cetylate and alpha-tocopherol acetate; Described polyethyleneglycol glyceride refers to one or more in Polyethylene Glycol Miglyol 812, Polyethylene Glycol glyceryl laurate ester, Polyethylene Glycol tristerin, Oleum Cocois polyethyleneglycol glyceride, almond oil polyethyleneglycol glyceride, polyoxyethylene (25) triolein and the polyethyleneglycol-12-hydroxy stearin (Solutol HS 15).
Described pH adjusting agent refers to one or more in citric acid, malic acid, tartaric acid, fumaric acid and the citric acid.
Cosolvent of the present invention refers to that in Polyethylene Glycol, the TC one or both share; The mean molecule quantity of described Polyethylene Glycol is 200-6000, and preferred molecular weight is 200,300,400,600,800.
Metal-chelator of the present invention refers to two edetates and derivant thereof, any in diethylenetriamine pentaacetic acid and derivant thereof and ethylene glycol-two-(2-amino-ethyl) tetraacethyl or several; Antioxidant refers to vitamin E, vitamin C, sodium sulfite, sodium pyrosulfite, one or more in cysteine and the salt thereof.
The preparation method of pharmaceutical composition of the present invention comprises a kind of in the following method:
Etoposide is joined in the mixture that is comprised of oil phase, surfactant, cosolvent, pH adjusting agent, and 30 ℃ of-80 ℃ of stirring in water bath dissolvings obtain pre-emulsifying concentrated solution;
Or first etoposide is mixed with cosolvent, again with oil phase, surfactant mix homogeneously, adding pH adjusting agent, 30 ℃ of-80 ℃ of stirring in water bath dissolvings obtain pre-emulsifying concentrated solution;
Or first cosolvent is mixed with pH adjusting agent, add the etoposide mixing, again with oil phase, surfactant mixing, 30 ℃ of-80 ℃ of stirring in water bath dissolvings obtain pre-emulsifying concentrated solution.
The preparation method of pharmaceutical composition of the present invention is preferably as follows a kind of in the method:
Etoposide is joined in the mixture that is comprised of oil phase, surfactant, cosolvent, pH adjusting agent, and 35 ℃ of stirring in water bath dissolvings obtain pre-emulsifying concentrated solution;
Or etoposide mixed with cosolvent first, again with oil phase, surfactant mix homogeneously, the adding pH adjusting agent, 45 ℃ of stirring in water bath are dissolved, and obtain pre-emulsifying concentrated solution;
Or first cosolvent is mixed with pH adjusting agent, add the etoposide mixing, again with oil phase, surfactant mixing, 55 ℃ of stirring in water bath dissolvings obtain pre-emulsifying concentrated solution.
The ratio of weight portion of the present invention and parts by volume is g/ml.
Description of drawings:
Fig. 1: emulsification times
Fig. 2: stripping curve
The present invention screens by great many of experiments, found etoposide to form from the prescription of (little) emulsifying systems (being pre-emulsifying concentrated solution), this concentrated solution clarification, transparent, not stratified, and have that content of dispersion is high, adjuvant toxicity is low and consumption is few, emulsive rate is fast, the uniform characteristics of particle diameter.The present invention does not adopt isopropyl myristate fully, but adopts (can be oral) such as the medium chain fatty acid ester that now gone through can be used for human body (now can oral or injection) or 1944, has very strong practicality, can realize immediately suitability for industrialized production.Content of dispersion is higher than bibliographical information, efficiently solve simultaneously meet water unstable, easily crystallize, contain ethanol and make the problems such as Stability of Soft Capsules reduction.In addition, etoposide is designed and produced into self-micro emulsion formulation, emulsion particle diameter can reach tens nanometers after the emulsifying, can effectively reduce the existing problem that the soft capsule oral individual variation is large, bioavailability is low.
But this system can be further development of the Pharmaceutical composition that the basic per os that is comprised of above-mentioned pre-emulsifying concentrated solution in the pharmaceutically acceptable diluent gives, but the oral administration biaavailability of the pharmaceutically Pharmaceutical composition of the parenteral that is basically formed by the pre-emulsifying concentrated solution of the present invention injection in the acceptable diluent, and pre-emulsifying concentrated solution of the present invention when increasing etoposide and be applied to receptor, reduce the application in the individual variation.This invention is especially significant to solving the existing existing problem of etoposide preparations.
The present invention makes etoposide better bring into play curative effect, the dissolubility that improves etoposide improves bioavailability, improve the stability of etoposide, advantage efficient, low toxicity with novel form is given full play to the etoposide anti-tumor activity and is reduced toxic and side effects, will promote undoubtedly the application of etoposide in clinical.
Following experimental example and embodiment are used for further specifying but are not limited to the present invention.
The mensuration of experimental example 1 content of dispersion
The employing high performance liquid chromatography has been investigated the medicament contg among the embodiment 1～6, and structure shows: concentrated solution Chinese medicine content is the 95%-105% of sign amount, shows that preparation of the present invention and preparation method have good homogeneity and industrial applicibility.
Table 1 sample content of dispersion detects result of the test
Experimental example 2 average emulsification times are measured
Will be according to the etoposide pre-emulsifying concentrated solution of preparation among the embodiment 1～15, be placed in 37 ℃ the simulated gastric fluid, gentle agitation (50 rev/mins) is to fully emulsifying (solvent homogeneous, without layering), the record mixing time records average emulsification times all in 15min.See Fig. 1.
Experimental example 3 particle diameters detect
Size is the principal element that affects drug absorption in the emulsification preparation, the particle diameter of emulsion droplet is less within the specific limits, bioavailability is better, and after the complete emulsifying of etoposide pre-emulsifying concentrated solution according to preparation among the embodiment 1～15, average emulsion droplet particle diameter is all less than 150nm.
Experimental example 4 dissolution determinations
Method inspection according to dissolution test method (two appendix of Chinese Pharmacopoeia version in 2000), according to the etoposide pre-emulsifying concentrated solution that makes among the embodiment 1～15, measurement result is that stripping in 30 minutes is greater than 85%, by measurement result as seen, the dissolution of the etoposide pre-emulsifying concentrated solution of preparation (two appendix of Chinese Pharmacopoeia version in 2000) up to specification.See Fig. 2.
Following examples are used for further specifying but are not limited to the present invention.
The specific embodiment
Embodiment 1:
Sad Kui acid glycerol three ester 1g PEG400 2.5g
Malic acid 0.1g polyoxyethylene ether (35) Oleum Ricini 2.7g
Etoposide 0.4g
Take by weighing sad Kui acid glycerol three esters, PEG400, polyoxyethylene ether (35) Oleum Ricini and malic acid, mixing adds etoposide, and 60 ℃ of stirring in water bath dissolvings namely get the etoposide pre-emulsifying concentrated solution.
Embodiment 2:
Inferior oleoyl polyethyleneglycol glyceride 0.7g Tween60 6g
Etoposide 0.41g PEG400 3g
Tartaric acid 0.1g
Take by weighing inferior oleoyl polyethyleneglycol glyceride, PEG400, Tween60 and tartaric acid, mixing adds etoposide, and 50 ℃ of stirring in water bath dissolvings namely get the etoposide pre-emulsifying concentrated solution.
Embodiment 3:
Linoleic acid polyethyleneglycol glyceride 1g a-tocopherol cetylate 3.6g
Etoposide 0.5g PEG400 4.8g
Citric acid 0.1g
Take by weighing linoleic acid polyethyleneglycol glyceride, PEG400, alpha-tocopherol cetylate and citric acid, mixing adds etoposide, and 40 ℃ of stirring in water bath dissolvings namely get the etoposide pre-emulsifying concentrated solution.
Embodiment 4:
Oleoyl polyethyleneglycol glyceride 1g Tween 80 4.8g
TC 0.5g etoposide 0.5g
PEG400 3.6g citric acid 0.1g
Take by weighing PEG400 and citric acid, add oleoyl polyethyleneglycol glyceride, Tween 80 and TC, mixing, 40 ℃ of stirring in water bath add etoposide, and dissolving namely gets the etoposide pre-emulsifying concentrated solution.
Embodiment 5:
Stearoyl polyoxy glyceride 0.7g alpha-tocopherol polyethylene glycol succinate 4g
TC 1g etoposide 0.6g
PEG400 3.6g fumaric acid 0.1g
Take by weighing PEG400 and fumaric acid, add etoposide, add again stearoyl polyoxy glyceride, TC and alpha-tocopherol polyethylene glycol succinate, mixing, 55 ℃ of stirring in water bath, dissolving namely gets the etoposide pre-emulsifying concentrated solution.
Embodiment 6:
Inferior oleoyl polyethyleneglycol glyceride 1.3g polyoxyethylene (25) triolein 3g
Etoposide 0.6g TC 5g
Fumaric acid 0.1g
Take by weighing PEG400 and fumaric acid, add etoposide, add again linoleic acid polyethyleneglycol glyceride, TC, mixing, 65 ℃ of stirring in water bath, dissolving namely gets the etoposide pre-emulsifying concentrated solution.
Embodiment 7:
Oleum helianthi glyceride 0.7g polyoxyethylene ether (35) Oleum Ricini 6g
TC 0.45g etoposide 0.6g
PEG400 3g citric acid 0.1g
Take by weighing PEG400, Oleum helianthi glyceride, TC, polyoxyethylene ether (35) Oleum Ricini and citric acid, mixing adds etoposide again, 50 ℃ of stirring in water bath, and dissolving namely gets the etoposide pre-emulsifying concentrated solution.
Embodiment 8:
Sad certain herbaceous plants with big flowers acid glycerol three ester 1.3g Labraso 3g
Etoposide 0.6g TC 5g
Citric acid 0.1g
Take by weighing TC, sad certain herbaceous plants with big flowers acid glycerol three esters, Labraso and citric acid, mixing adds etoposide again, 60 ℃ of stirring in water bath, and dissolving namely gets the etoposide pre-emulsifying concentrated solution.
Embodiment 9:
Oleoyl polyethyleneglycol glyceride 1g CREMOPHORE EL 1.35g
PEG400 1.35g TC 1.35g
Citric acid 0.1g
Take by weighing PEG400, TC, citric acid, mixing adds oleoyl polyethyleneglycol glyceride, CREMOPHORE EL and polyoxyl 40 hydrogenated castor oil again, mixing adds etoposide at last, 55 ℃ of stirring in water bath, dissolving namely gets the etoposide pre-emulsifying concentrated solution.
Embodiment 10:
Olein 1g CREMOPHORE EL 1.35g
Polyethyleneglycol-12-hydroxy stearin 1.35g etoposide 0.39g
TC 2.7g citric acid 0.1g
Take by weighing TC, citric acid, mixing adds CREMOPHORE EL, polyethyleneglycol-12-hydroxy stearin and olein again, mixing adds etoposide at last, 40 ℃ of stirring in water bath, dissolving namely gets the etoposide pre-emulsifying concentrated solution.
Embodiment 11:
Kui acid glyceride 1g CREMOPHORE EL 1.5g
TC 5.2g polyoxyl 40 hydrogenated castor oil 1.5g
Etoposide 0.7g PEG400 0.7g
Citric acid 0.1g
Take by weighing TC, PEG400, citric acid, mixing adds CREMOPHORE EL and polyoxyl 40 hydrogenated castor oil, Kui acid glyceride again, mixing adds etoposide at last, 70 ℃ of stirring in water bath, dissolving namely gets the etoposide pre-emulsifying concentrated solution.
Embodiment 12:
Trivent OCG 2g PEG400 4.0g
Tartaric acid 0.1g CREMOPHORE EL 3.75g
Etoposide 0.25g
Take by weighing PEG400, tartaric acid, CREMOPHORE EL, Trivent OCG, etoposide, mixing, 40 ℃ of stirring in water bath, dissolving namely gets the etoposide pre-emulsifying concentrated solution.
Embodiment 13:
Miglyol 812N 0.7g CREMOPHORE EL 1.25g
Polyethyleneglycol-12-hydroxy stearin 1.25g etoposide 0.9g
TC 5.8g citric acid 0.1g
Take by weighing TC, citric acid, mixing adds CREMOPHORE EL, polyethyleneglycol-12-hydroxy stearin, Miglyol 812N, mixing adds etoposide at last, 50 ℃ of stirring in water bath, dissolving namely gets the etoposide pre-emulsifying concentrated solution.
Embodiment 14:
Miglyol 812N 1g PEG400 2.5g
CREMOPHORE EL 5g etoposide 0.4g
Citric acid 0.1g
Take by weighing above-mentioned every, mixing, 40 ℃ of stirring in water bath, the dissolving, namely get the etoposide pre-emulsifying concentrated solution.
Embodiment 15:
Inferior oleoyl polyethyleneglycol glyceride 0.8g Polyethylene Glycol glyceryl laurate ester 3.5g
Etoposide 0.36g polyoxyl 40 hydrogenated castor oil 2g
PEG400 2g tartaric acid 0.1g
Take by weighing PEG400, tartaric acid, Polyethylene Glycol glyceryl laurate ester, polyoxyl 40 hydrogenated castor oil, inferior oleoyl polyethyleneglycol glyceride, etoposide, mixing, 40 ℃ of stirring in water bath, dissolving namely gets the etoposide pre-emulsifying concentrated solution.
Claims (10)
1. pharmaceutical composition is characterized in that the raw material of this pharmaceutical composition consists of:
Oil phase 0.5-2 weight portion etoposide 0.2-1 weight portion
Emulsifying agent 2-6 weight portion cosolvent 1.5-6 weight portion
PH adjusting agent 0.05-0.15 weight portion;
Wherein said oil phase is that the fatty acid carbons chain length is at medium chain fatty acid ester, long-chain fat acid glyceride or the polyethyleneglycol glyceride of C8-C14 scope; Described emulsifying agent is: one or both in polysorbate60, the polysorbate80; Or in the CREMOPHORE EL, Emulsifier EL-40, polyoxyl 40 hydrogenated castor oil, Cremophor RH60 one or more; Or polyethyleneglycol-12-hydroxy stearin; Described cosolvent refers to that in Polyethylene Glycol and the TC one or both share, and the mean molecule quantity of described Polyethylene Glycol is 300,400 or 600; Described pH adjusting agent is one or more in citric acid, malic acid, tartaric acid, fumaric acid or the citric acid.
2. pharmaceutical composition as claimed in claim 1 is characterized in that the raw material of this pharmaceutical composition consists of:
Oil phase 1 weight portion etoposide 0.4 weight portion
Emulsifying agent 2.7 weight portion cosolvents 2.5 weight portions
PH adjusting agent 0.08 weight portion.
3. pharmaceutical composition as claimed in claim 1 is characterized in that the raw material of this pharmaceutical composition consists of:
Oil phase 1 weight portion etoposide 0.36 weight portion
Emulsifying agent 5 weight portion cosolvents 2.5 weight portions
PH adjusting agent 0.1 weight portion.
4. pharmaceutical composition as claimed in claim 1 is characterized in that the raw material of this pharmaceutical composition consists of:
Oil phase 1 weight portion etoposide 0.5 weight portion
Emulsifying agent 3.6 weight portion cosolvents 4.8 weight portions
PH adjusting agent 0.12 weight portion.
5. pharmaceutical composition as claimed in claim 1 is characterized in that the raw material of this pharmaceutical composition consists of:
Oil phase 1 weight portion etoposide 0.7 weight portion
Emulsifying agent 3 weight portion cosolvents 5.9 weight portions
PH adjusting agent 0.14 weight portion.
6. drug regimen agent as claimed in claim 1 is characterized in that the raw material of this pharmaceutical composition consists of:
Oil phase 0.9 weight portion etoposide 0.4 weight portion
Emulsifying agent 5.5 weight portion cosolvents 3 weight portions
PH adjusting agent 0.11 weight portion.
7. pharmaceutical composition as claimed in claim 1 is characterized in that the raw material of this pharmaceutical composition consists of:
Oil phase 0.8 weight portion etoposide 0.6 weight portion
Emulsifying agent 4 weight portion cosolvents 4.6 weight portions
PH adjusting agent 0.12 weight portion.
8. pharmaceutical composition as claimed in claim 1 is characterized in that the raw material of this pharmaceutical composition consists of:
Oil phase 0.7 weight portion etoposide 0.9 weight portion
Emulsifying agent 2.5 weight portion cosolvents 5.5 weight portions
PH adjusting agent 0.14 weight portion.
9. pharmaceutical composition as claimed in claim 1 is characterized in that the raw material of this pharmaceutical composition consists of:
Oil phase 1.3 weight portion etoposides 0.6 weight portion
Emulsifying agent 3 weight portion cosolvents 5 weight portions
PH adjusting agent 0.12 weight portion.
10. such as the arbitrary described pharmaceutical composition of claim 1-9, it is characterized in that:
Described fatty acid carbons chain length refers in sad Kui acid glycerol three esters, Trivent OCG, the Kui acid glyceride one or more in the medium chain fatty acid ester of C8-C14 scope; Described long-chain fat acid glyceride is oleic acid sorbitol ester, olein, glyceryl linoleate and/or Oleum helianthi glyceride; Described polyethyleneglycol glyceride is one or more in oleoyl polyethyleneglycol glyceride, inferior oleoyl polyethyleneglycol glyceride and the stearoyl polyoxy glyceride.
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| CN103520100A (en) * | 2012-07-04 | 2014-01-22 | 天津药物研究院 | Etoposide self-microemulsion preparation as well as preparation method and application thereof |
| CN103211781B (en) * | 2013-03-21 | 2014-07-30 | 青岛正大海尔制药有限公司 | Etoposide soft capsule |
| CN104706585A (en) * | 2013-12-16 | 2015-06-17 | 天津迈迪瑞康生物医药科技有限公司 | Vinorelbine bitartrate fat emulsion concentrated solution, preparation method and application thereof |
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| CN1973826A (en) * | 2006-12-18 | 2007-06-06 | 沈阳药科大学 | Injection containing lipoid microsphere of etoposide and its prepn process |
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| CN1973826A (en) * | 2006-12-18 | 2007-06-06 | 沈阳药科大学 | Injection containing lipoid microsphere of etoposide and its prepn process |
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