CN1795870A - Medication composition of containing - Google Patents
Medication composition of containing Download PDFInfo
- Publication number
- CN1795870A CN1795870A CN 200410101404 CN200410101404A CN1795870A CN 1795870 A CN1795870 A CN 1795870A CN 200410101404 CN200410101404 CN 200410101404 CN 200410101404 A CN200410101404 A CN 200410101404A CN 1795870 A CN1795870 A CN 1795870A
- Authority
- CN
- China
- Prior art keywords
- acid
- etoposide
- pharmaceutical composition
- propylene glycol
- excipient
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
Landscapes
- Medicinal Preparation (AREA)
Abstract
A composite medicine containing etoposide in the form of freeze-dried powder injection contains etoposide, organic acid, polyethanediol 400, propanediol and excipient. It has high stability.
Description
[technical field]
The present invention relates to pharmaceutical composition of a kind of etoposide and preparation method thereof, particularly etoposide freeze-dry powder agent and preparation method thereof.
[background technology]
Etoposide is a kind of Cytotoxic broad-spectrum anti-tumor medicine, and its pharmacokinetics has two key properties: (1) is because etoposide is that reversibility combines with topoisomerase II, and etoposide acts on long-term S phase and G in the cell cycle
2Phase, thereby the length of blood drug level persistent period is bigger to the drug effect influence than peak concentration height is that typical time dependence medicine is [referring to Cavalli F, Sonntag RW, Jung F, et al.VP-16-213monotherapy for remission induction of small cell lung cancer:arandomized trial using three dosages chedules.Cancer TreatRep, 1978,62:473]; (2) when plasma concentration at 1～3mg.L
-1The time, cellulotoxic effect is better, and bone marrow toxicity is also lighter, as plasma concentration 5mg.L
-1Antitumous effect increases not obvious, and bone marrow toxicity obviously strengthens [referring to Wofll SN, Grosh WW, Prater K, et al.In vitro pharmacodynamic evaluation of VP-16-213 andimplications for chemotherapy.Cancer Chemother Pharmacol.1978,19:246].At present, be used for clinical etoposide two kinds of dosage forms are arranged: oral soft capsule agent and injection.But, existing problems are in soft capsule: (1) etoposide dissolubility is bad, degraded easily under the gastric acid effect, (2) because of individual variation, oral dosage form bioavailability changes greatly, and availability is lower, do not wait from 25%-74%, in order to prolong effective blood drug level, certainly will to increase medicining times or increase medication dose, cause toxic and side effects to increase; The problem that exists in the injection is that (1) is liquid preparation, and less stable has higher requirement for storage and transportation, is subjected to bigger restriction in the use.(2) pH value of injection is less than 4, and added antipathogenic composition, and is bigger to the zest of human body.There is the enteric slow (control) of unit development etoposide to release solid dispersed formulation at present, and apply for a patent (application number: 02153962.6), but still can not reach the stable effective blood drug concentration that intravenous injection can reach, for this reason, be badly in need of clinically a kind ofly effectively changing the insufficient novel form that contains etoposide of said medicine.
[summary of the invention]
The problem to be solved in the present invention is to develop the dissolubility that can increase etoposide and be applicable to intravenous injection, can keep the solid pharmaceutical composition of effective blood drug concentration the long period.
We find in surprise in the experiment, propylene glycol has good promotion dissolution for the present invention, after Polyethylene Glycol adds an amount of propylene glycol, can unexpectedly solve the solubility problem of etoposide, increase the stability of etoposide under the liquid condition, this has created good condition for the lower used for intravenous injection etoposide freeze-dry powder of preparation zest.
The invention provides a kind of etoposide freeze-dry powder agent, contain following weight ratio medicine:
Etoposide 40 organic acid 5～50
PEG400 1200～2400 propylene glycol 200～400
Excipient 600～1200.
Excipient in the pharmaceutical composition of the present invention is selected from one or more in mannitol, sorbitol, xylitol, glycine, aspartic acid, the glucose, and preferred weight ratio is 1000.
Organic acid in the pharmaceutical composition of the present invention is one or more in citric acid, tartaric acid, valeric acid, malic acid, salicylic acid, the gallic acid.
In the present invention, the consumption of Polyethylene Glycol is 1200～2400 (weight ratios), and preferred 1800～2200 (weight ratios), the amount of propylene glycol are 200～400 (weight ratios), preferred 300 (weight ratios).
In addition, etoposide itself need can be stablized under sour environment, according to the difference of excipient, and organic acid use amount difference.Therefore our selected organic acid use amount is 5～50 (weight ratios).
The present invention also provides the preparation method of this powder pin:
A. the mixed liquor of etoposide with PEG400 and propylene glycol fully dissolved;
B. excipient and organic acid are dissolved with suitable quantity of water;
C. two kinds of solution that a and b are made mix;
D. the mixed liquor that c is made is removed the pyrogen postlyophilization, gets this product.
Dissolving described in the preparation method of the present invention refers to utilize pharmaceutically the conventional method dissolving, as: heating, ultrasonic, stirring etc.
[specific embodiment]
Embodiment 1
Etoposide 40mg citric acid 5mg PEG400 1200mg
Propylene glycol 200mg mannitol 600mg
A. the mixed liquor of etoposide with PEG400 and propylene glycol fully dissolved;
B. with mannitol and citric acid 4ml water dissolution;
C. two kinds of solution that a and b are made mix;
D. the mixed liquor that c is made is removed the pyrogen postlyophilization, gets this product.
Embodiment 2
Etoposide 40mg tartaric acid 6.5mg PEG400 2100mg
Propylene glycol 300mg mannitol 800mg xylitol 200mg
A. the mixed liquor of etoposide with PEG400 and propylene glycol fully dissolved;
B. with mannitol, xylitol and tartaric acid 7ml water dissolution;
C. two kinds of solution that a and b are made mix;
D. the mixed liquor that c is made is removed the pyrogen postlyophilization, gets this product.
Embodiment 3
Etoposide 40mg malic acid 25mg PEG400 1800mg
Propylene glycol 300mg mannitol 700mg glycine 200mg
Aspartic acid 100mg
A. the mixed liquor of etoposide with PEG400 and propylene glycol fully dissolved;
B. with mannitol, glycine, aspartic acid and malic acid 4ml water dissolution;
C. two kinds of solution that a and b are made mix;
D. the mixed liquor that c is made is removed the pyrogen postlyophilization, gets this product.
Embodiment 4
Etoposide 40mg citric acid 50mg PEG400 2200mg
Propylene glycol 400mg mannitol 500mg sorbitol 100mg
Glycine 600mg
A. the mixed liquor of etoposide with PEG400 and propylene glycol fully dissolved;
B. with mannitol, sorbitol, glycine and citric acid acid 5ml water dissolution;
C. two kinds of solution that a and b are made mix;
D. the mixed liquor that c is made is removed the pyrogen postlyophilization, gets this product.
The contrast experiment: different solvents is for the dissolubility of etoposide
A: Polyethylene Glycol B: propylene glycol C:A+B
| Project | A | B | C |
| 1200mg | 300mg | A+B | |
| Etoposide 30mg | Separate than indissoluble, time long (8h), the long-time back (24h) of placing has crystal to separate out | Can not dissolve | Yi Rong, (24h) solution is as clear as crystal after long-time the placement |
Claims (6)
1, a kind of pharmaceutical composition that contains etoposide, the every dosage of described pharmaceutical composition contains following weight ratio ingredient:
Etoposide 40 organic acid 5～50
PEG400 1200～2400 propylene glycol 200～400
Excipient 600～1200.
2, the described pharmaceutical composition of claim 1, the weight ratio of PEG400 is 1800～2200, the weight ratio of propylene glycol is 300.
3, the described pharmaceutical composition of claim 1, organic acid is one or more in citric acid, tartaric acid, valeric acid, malic acid, salicylic acid, the gallic acid.
4, the described pharmaceutical composition of claim 1, excipient is selected from one or more in mannitol, sorbitol, xylitol, glycine, aspartic acid, the glucose.
5, the described pharmaceutical composition of claim 1, the weight ratio of excipient is 1000.
6, the described preparation of drug combination method of claim 1 to 5:
A. the mixed liquor of etoposide with PEG400 and propylene glycol fully dissolved;
B. excipient and organic acid are dissolved with suitable quantity of water;
C. two kinds of solution that a and b are made mix;
D. the mixed liquor that c is made is removed the pyrogen postlyophilization, gets this product.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 200410101404 CN1795870A (en) | 2004-12-20 | 2004-12-20 | Medication composition of containing |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 200410101404 CN1795870A (en) | 2004-12-20 | 2004-12-20 | Medication composition of containing |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN1795870A true CN1795870A (en) | 2006-07-05 |
Family
ID=36817325
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN 200410101404 Pending CN1795870A (en) | 2004-12-20 | 2004-12-20 | Medication composition of containing |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN1795870A (en) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103211772A (en) * | 2013-03-21 | 2013-07-24 | 青岛正大海尔制药有限公司 | Etoposide lyophilized powder for injection |
| CN103211781A (en) * | 2013-03-21 | 2013-07-24 | 青岛正大海尔制药有限公司 | Etoposide soft capsule |
-
2004
- 2004-12-20 CN CN 200410101404 patent/CN1795870A/en active Pending
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103211772A (en) * | 2013-03-21 | 2013-07-24 | 青岛正大海尔制药有限公司 | Etoposide lyophilized powder for injection |
| CN103211781A (en) * | 2013-03-21 | 2013-07-24 | 青岛正大海尔制药有限公司 | Etoposide soft capsule |
| CN103211772B (en) * | 2013-03-21 | 2014-07-23 | 青岛正大海尔制药有限公司 | Etoposide lyophilized powder for injection |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JP4890732B2 (en) | Paclitaxel / liposome composition for cancer treatment and method for producing the same | |
| US20070060627A1 (en) | Organic compounds | |
| KR20100044237A (en) | Compositions for the treatment of neoplastic diseases | |
| CN1371366A (en) | Benzamide formulation with histone deacetylase inhibitor activity | |
| CN1612737A (en) | Platinum derivative pharmaceutical formulations | |
| US6683100B2 (en) | Organic compounds | |
| WO2011014541A1 (en) | Stable formulations of azacitidine | |
| JP5404625B2 (en) | Composition | |
| RU2557919C1 (en) | Free-flowing compressible rapamycin powder and thereof-based pharmaceutical composition | |
| CN1373667A (en) | Formulations for parenteral use of estramustine phosphate and amino acids | |
| CN1795870A (en) | Medication composition of containing | |
| CA2487070A1 (en) | Aqueous fludarabine phosphate composition | |
| US8227430B2 (en) | Injectable, injection solution, and injection kit preparation | |
| CN1839800A (en) | Vinorelbine Bitartrate lipsome freeze-drying powder injection and its preparation method | |
| KR102161866B1 (en) | Composition of cabazitaxel and sulfobutylether beta-cyclodextrin | |
| CN1883467A (en) | Orally administered anti-tumor medicinal composition of taxane and administration method thereof | |
| EP4216980B1 (en) | C-phycocyanin for use in the treatment and/or prevention of peripheral neuropathy | |
| CN1899296A (en) | Breviscapine B injection preparation and its preparing method | |
| CN1374857A (en) | Formulations for parenteral use of estramustine phosphate and sulfoalkyl ether cyclodextrins | |
| CN1511037A (en) | Nonintestinal estramustine phosphate and albumin preparations | |
| CN1850097A (en) | Scutellarin injection preparation and its preparing method | |
| CN1177583C (en) | For mulations for parenteral use of estramustine phosphate with improved pharmacological properties | |
| CN1290506C (en) | Medicinal composition | |
| CN1839811A (en) | Lomustine liposome freeze-drying powder injection and its preparation method | |
| CN1895252A (en) | Zirasitone mesylate soluble medicinal preparation |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C02 | Deemed withdrawal of patent application after publication (patent law 2001) | ||
| WD01 | Invention patent application deemed withdrawn after publication |