CN103385883B - Pharmaceutical composition containing tropisetron hydrochloride and fructose - Google Patents
Pharmaceutical composition containing tropisetron hydrochloride and fructose Download PDFInfo
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- CN103385883B CN103385883B CN201310332615.XA CN201310332615A CN103385883B CN 103385883 B CN103385883 B CN 103385883B CN 201310332615 A CN201310332615 A CN 201310332615A CN 103385883 B CN103385883 B CN 103385883B
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- injection
- fructose
- navoban
- soz
- pharmaceutical composition
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Abstract
The invention relates to a pharmaceutical composition containing a tropisetron hydrochloride injection and a fructose injection, and particularly relates to a composite application package comprising the tropisetron hydrochloride injection and the fructose injection. In use, the tropisetron hydrochloride injection is dissolved into the fructose injection, and then the mixture is used for intravenous infusion. The pharmaceutical composition containing the tropisetron hydrochloride injection and the fructose injection has the effect of treating postoperative nausea and emesis, and also is capable of replenishing energy and body fluid of human body.
Description
Technical field
The present invention relates to the pharmaceutical composition of a kind of hydrochloric tropisetron and fructose, be specifically related to a kind of drug regimen application packages be made up of Navoban (Soz) injection and fructose injection, belong to medical art.
Background technology
Former and the central nervous system's 5-hydroxy tryptamine 3(5-HT3 of a kind of peripheral nervous of Navoban (Soz)) efficient, the high selectivity competition antagonist of receptor.Cucumber comprises some chemotherapeutic and the class pheochromocyte of internal organs mucosa can be excited to discharge 5-hydroxy tryptamine, thus brings out the nauseating vomiting reflex of companion.Navoban (Soz) suppresses vomiting reflex mainly through optionally blocking the former presynaptic 5-HT3 receptor of peripheral nervous, in addition, its antiemetic effect also may suppress vagal stimulation of area postrema relevant by the direct blocking-up to maincenter 5-HT3 receptor with it.
The elimination half-life (β phase) of Navoban (Soz) Metabolism of Normal person is about 7 ~ 10 hours, and in the bad person of metabolism, this value may extend to 45 hours.The CLTB of this product is about 1 liter/min, and that wherein removes through kidney is about 10%.In the patient that metabolism is bad, although the constant rate removed through kidney, CLTB reduces to 0.1 ~ 0.2 liter/min.This reduction can cause eliminating Increased Plasma Half-life about 4 ~ 5 times, AUC value raising 5 ~ 7 times, and Cmax and distribution volume and homergy person are without marked difference.In the bad person of metabolism, the medicine prototype ratio of discharging through urine is large compared with Metabolism of Normal person.
Navoban (Soz) is used for the nausea and vomiting that prevention and therapy cancer chemotherapy causes.Treat postoperative Nausea and vomiting.
Fructose (D-fructose) is a kind of left-handed hexose, is the isomer of glucose, energy and body fluid supplement.Fructose more easily forms glycogen than glucose, and mainly pass through fructokinase metabolism at liver, being easy to metabolism is fruit acid, is converted into energy rapidly.Pharmacokinetic data shows, Healthy People continues input fructose can reach steady plasma-drug concentration 6 ~ 8 mM/ls, in body, ATP and Phos all drop to steady-state level, hepatic clearance be 0.53 ml/g (liver is heavy)/minute, endocellular metabolism meets first order kinetics process.Fructose pharmacological action is substantially identical with glucose, has direct heat supply, supplements effect of body fluid and nutrition whole body.After fructose intravenously administrable, metabolism is but fast than glucose in vivo, is easily absorbed by body, and does not rely on insulin, little to blood sugar influence, is more suitable for diabetes, hepatopathy patients supply energy, supplements body fluid.
Fructose is under the insulin-resistant states such as postoperative infection of burning or be not suitable for need keeping the skin wet when using glucose or the body fluid supplement therapy of patient of the energy.
Prior art treats postoperative nausea and vomiting in Navoban (Soz) operation instructions, venoclysis (be dissolved in normal saline, Ringers solution, 5% glucose solution or fructose soln etc.) or slowly intravenous injection (more than 30 seconds).Need to buy use in conjunction respectively in Clinical practice, the assembly packaging of Navoban (Soz) injection and fructose does not occur commercially with in medical institutions.
Applicant finds that the Navoban (Soz) injection and fructose injection by adopting particular excipient formation is supplied to medical institutions and market with the form of assembly packaging, is not only of great benefit to the stability of each drug alone; And improve its drug effect.
Summary of the invention
An object of the present invention, provides the pharmaceutical composition of a kind of Navoban (Soz) and fructose.
An object of the present invention, provides a kind of drug regimen application packages be made up of Navoban (Soz) injection and fructose injection, and wherein, Navoban (Soz) injection is sterile freeze-drying preparation or aseptic parenteral solution, and fructose injection is aseptic parenteral solution.
Combination application packaging provided by the invention, usage is for be dissolved in fructose injection posterior vein infusion by Navoban (Soz) injection.
Combination application packing specification provided by the invention is that Navoban (Soz) injection 2mg or 5mg or 2ml:2mg or 5ml:5mg(is by C
17h
20n
2o
2meter), fructose injection 250-500ml.
Preferably implement as the present invention one, fructose injection can be injected for fructose.
Navoban (Soz) injection of the present invention comprises Navoban (Soz) injection and hydrochloride for injection tropisetron lyophilized injectable powder, adds the aseptic parenteral solution of appropriate auxiliaries or add the sterile freeze-drying preparation that appropriate excipient makes for Navoban (Soz).
As one of specific embodiment, concrete component and consumption as follows:
Wherein the proportioning of xylitol and glycine is 1:2.
Present invention also offers a kind of preparation method of Navoban (Soz) injection, concrete steps are:
(1) in material-compound tank, the water for injection of recipe quantity 80% is first added, temperature control 10 DEG C ~ 20 DEG C;
(2) add xylitol and the glycine of recipe quantity, stirring and dissolving is complete;
(3) add the Navoban (Soz) of recipe quantity, stirring and dissolving is complete, regulates pH to be 4.5-5.5 with 1mol/L sodium hydroxide solution or 1mol/L hydrochloric acid solution;
(4) add total amount 0.02%(g/ml) injection-use activated carbon, add residue water for injection, standardize solution, stirring and adsorbing 30 minutes;
(5) solution coarse filtration takes off charcoal, through 0.45 μm of cartridge filter coarse filtration, then uses 0.22 μm of microporous filter membrane aseptic filtration qualified to visible foreign matters;
(6) fill, sealing, sterilizing, obtains Navoban (Soz) injection; Or fill, lyophilization, obtains hydrochloride for injection tropisetron.
As the present invention one preferred embodiment, wherein in preparation method, lyophilized injectable powder freeze drying process is:
1. the pre-freeze phase, shelf temperature is cooled to-40 DEG C ± 2 DEG C, when products temperature reaches-35 DEG C ± 2 DEG C, (approximately needs 3 hours), be incubated about 2 hours, make product freeze reality completely;
2. distil the phase, when in case, force value reaches below 10Pa, arranging flaggy temperature is-4 DEG C ± 2 DEG C, and arranging dry case vacuum is 30Pa, slowly heat up to flaggy, product starts to distil (plate temperature rises to-4 DEG C ± 2 DEG C by-40 DEG C ± 2 DEG C) under vacuum.Shelf temperature rises to-4 DEG C ± 2 DEG C, after ice crystal disappears, be incubated about 2 hours;
3. dry period, arranging flaggy temperature is 30 DEG C, and flaggy continues slowly to heat up, and product carries out drying (plate temperature rises to 30 DEG C ± 1 DEG C by-4 DEG C ± 2 DEG C and about needs 2 hours) under vacuum; Shelf temperature reaches 30 DEG C ± 1 DEG C, and products temperature is warming up to about 20 DEG C ± 2 DEG C, is incubated about 2 ~ 3 hours, terminates lyophilizing, carries out pressing full plug.
Fructose injection of the present invention is fructose injection, is the sterile water solution of fructose further.
As one of specific embodiment, concrete component and consumption as follows:
Present invention also offers a kind of preparation method of fructose injection, concrete steps are:
(1) densely to join: the water for injection adding recipe quantity 30% in dense preparing tank, add the fructose of recipe quantity, stirring makes it to dissolve, add recipe quantity 0.1%(g/ml) moistening medicinal charcoal, stir 30 minutes, filtering decarbonization, filters into dilute preparing tank, repeatedly rinse dense preparing tank with water for injection, and filter into dilute preparing tank;
(2) rarely to join: in dilute preparing tank, add the water for injection to recipe quantity 90%, be 3.8-4.0 by 0.1mol/L hydrochloric acid solution adjust ph, add recipe quantity 0.1%(g/ml) moistening medicinal charcoal, stir 30 minutes, filtering decarbonization, benefit adds to the full amount of water for injection;
(3) with the microporous filter membrane fine straining of 0.22 μm, fill, sealing;
(4) sterilizing: 121 DEG C of pressure sterilizings 15 minutes, quick spraying cooling, offers for sale, and naturally cools to room temperature.
The Combination application that present invention also offers a kind of Navoban (Soz) injection and fructose injection is packaged in the nausea and vomiting prepared Therapeutic cancer chemotherapy and cause, the application in postoperative Nausea and vomiting etc.Not only there is the effect for the treatment of postoperative nausea and vomiting, and energy and the body fluid of human body can also be supplemented.
Detailed description of the invention
embodiment 1the preparation of hydrochloride for injection tropisetron
Prescription:
Preparation process:
(1) first 2800ml water for injection is added in a reservoir, temperature control 10 DEG C ~ 20 DEG C;
(2) add 35g xylitol and 70g glycine, stirring and dissolving is complete;
(3) Navoban (Soz) 7g(is added by C
17h
20n
2o
2meter), stirring and dissolving is complete, regulates pH to be 4.8 with 1mol/L sodium hydroxide solution or 1mol/L hydrochloric acid solution;
(4) add 0.7g injection-use activated carbon, add residue water for injection, be settled to 3500ml, stirring and adsorbing 30 minutes;
(5) solution coarse filtration takes off charcoal, through 0.45 μm of cartridge filter coarse filtration, then uses 0.22 μm of microporous filter membrane aseptic filtration qualified to visible foreign matters;
(6) fill.
(7) lyophilization
1. the pre-freeze phase, shelf temperature is cooled to-40 DEG C ± 2 DEG C, when products temperature reaches-35 DEG C ± 2 DEG C, (approximately needs 3 hours), be incubated about 2 hours, make product freeze reality completely;
2. distil the phase, when in case, force value reaches below 10Pa, arranging flaggy temperature is-4 DEG C ± 2 DEG C, and arranging dry case vacuum is 30Pa, slowly heat up to flaggy, product starts to distil (plate temperature rises to-4 DEG C ± 2 DEG C by-40 DEG C ± 2 DEG C) under vacuum.Shelf temperature rises to-4 DEG C ± 2 DEG C, after ice crystal disappears, be incubated about 2 hours;
3. dry period, arranging flaggy temperature is 30 DEG C, and flaggy continues slowly to heat up, and product carries out drying (plate temperature rises to 30 DEG C ± 1 DEG C by-4 DEG C ± 2 DEG C and about needs 2 hours) under vacuum; Shelf temperature reaches 30 DEG C ± 1 DEG C, and products temperature is warming up to about 20 DEG C ± 2 DEG C, is incubated about 2 ~ 3 hours, terminates lyophilizing, carries out pressing full plug.
(8) roll lid, to obtain final product.
comparative example 1the preparation of hydrochloride for injection tropisetron
Prescription:
Preparation process prepares according to the technique of embodiment 1.
embodiment 2the preparation of Navoban (Soz) injection
Prescription:
Preparation process:
(1) first 5600ml water for injection is added in a reservoir, temperature control 10 DEG C ~ 20 DEG C;
(2) add 35g xylitol and 70g glycine, stirring and dissolving is complete;
(3) Navoban (Soz) 7g(is added by C
17h
20n
2o
2meter), stirring and dissolving is complete, regulates pH to be 5.1 with 1mol/L sodium hydroxide solution or 1mol/L hydrochloric acid solution;
(4) add 1.4g injection-use activated carbon, add residue water for injection, be settled to 7000ml, stirring and adsorbing 30 minutes;
(5) solution coarse filtration takes off charcoal, through 0.45 μm of cartridge filter coarse filtration, then uses 0.22 μm of microporous filter membrane aseptic filtration qualified to visible foreign matters;
(6) fill, sealing, sterilizing.
comparative example 2the preparation of Navoban (Soz) injection
Prescription:
Preparation process is prepared into according to embodiment 2.
embodiment 3the preparation of fructose injection
Prescription:
Preparation process:
(1) densely to join: the water for injection adding 30L in dense preparing tank, adds 10000g fructose, stir and make it to dissolve, add the moistening medicinal charcoal of 100g, stir 30 minutes, filtering decarbonization, filter into dilute preparing tank, repeatedly rinse dense preparing tank with water for injection, and filter into dilute preparing tank;
(2) rarely to join: in dilute preparing tank, add the water for injection to 90L, be 4.0 by 0.1mol/L hydrochloric acid solution adjust ph, adds the moistening medicinal charcoal of 100g, stirs 30 minutes, filtering decarbonization, mend and inject water to 100L;
(3) with the microporous filter membrane fine straining of 0.22 μm, fill, 250ml/ bottle and 500ml/ bottle, sealing;
(4) sterilizing: 121 DEG C of pressure sterilizings 15 minutes, quick spraying cooling, offers for sale, and naturally cools to room temperature.
embodiment 4the preparation of assembly packaging medicine
Combination 1: embodiment 1A preparation 2mg and fructose injection 250ml.
Combination 2: embodiment 1B preparation 5mg and fructose injection 250ml.
Combination 3: embodiment 2C preparation 2ml:2mg and fructose injection 250ml.
Combination 4: embodiment 2D preparation 2ml:5mg and fructose injection 250ml.
Combination 5: comparative example 1A preparation 2mg and fructose injection 250ml.
Combination 6: comparative example 1B preparation 5mg and fructose injection 250ml.
Combination 7: comparative example 2C preparation 2ml:2mg and fructose injection 250ml.
Combination 8: comparative example 2D preparation 2ml:5mg and fructose injection 250ml.
Test example 1 pharmacology irritant test
Get the New Zealand Journal of Health Physical Education doe 24 of body weight 2.0-2.5kg, be divided into four groups at random.New zealand rabbit is placed in holder, first group of abdominal part hypodermic embodiment of the present invention 4 combines the medicine of 1, second group of abdominal part hypodermic embodiment of the present invention 4 combines the medicine of 3,3rd group of abdominal part hypodermic embodiment of the present invention 4 combines the medicine of 5,4th group of abdominal part hypodermic embodiment of the present invention 4 combines the medicine of 7, every new zealand rabbit injection 3ml, during injection and after injection, notes observing injection site with or without the stimulation such as red and swollen, congested, hemorrhage and downright bad.In last administration after 24 hours, by sacrifice of animal, drawn materials in injection site, carry out histopathologic examination.
Result of the test:
Perusal: first group and second group does not occur the irritant reaction such as obvious redness, hyperemia, necrosis, there is a small amount of irritant reaction such as red and swollen and downright bad in the new zealand rabbit injection site of the 3rd group and the 4th group.
Pathological examination: first group and second group: skin texture is normal, and epidermis is without thickening, and subcutaneous tissue has no the morphological changes such as hyperemia, edema, has no the changes such as inflammatory cell infiltration.
3rd group and the 4th group: epidermis thickens, subcutaneous tissue is congested, edema, has inflammatory cell infiltration.
Conclusion: assembly packaging product of the present invention is without obvious stimulation effect, and zest is far smaller than the product of prior art.
Test example 2 pharmacodynamics test
Get 40 rats, body weight (205 ± 10) g, be divided into 4 groups at random, wherein first group of intravenous injection embodiment of the present invention 4 combines the medicine of 1, second group of intravenous injection embodiment of the present invention 4 combines the medicine of 3,3rd group of intravenous injection embodiment of the present invention 4 combines the medicine of 5, and the 4th group of intravenous injection embodiment of the present invention 4 combines the medicine of 7.After administration, 2h takes a blood sample 48 hours.
High performance liquid chromatography is adopted to detect the blood drug level of Navoban (Soz).Use software 3p87 and WT1.4 to carry out data analysis, relevant pharmacokinetic parameters result is as following table.
As can be seen from the above experimental data, in four groups of compatible solution, first group and second group of solution and the embodiment of the present invention 4 combine 1 and the sample of combination 3 than the 3rd group and the 4th group of solution and the embodiment of the present invention 4 combine 5 and the sample bioavailability that combines 7 greatly improve, absolutely prove the intravenous benefit of assembly packaging of Navoban (Soz) injection of the present invention and fructose injection, injection is made to improve bioavailability widely, add drug effect, obtain unexpected technical effect.
Claims (2)
1. comprise a pharmaceutical composition for Navoban (Soz) injection and fructose injection, it is characterized in that Navoban (Soz) injection is the sterile freeze-drying preparation be made up of following composition;
Fructose injection is the aseptic parenteral solution be made up of following composition:
Fructose 50g 100g
Water for injection adds to 1000ml and adds to 1000ml.
2. comprise a pharmaceutical composition for Navoban (Soz) injection and fructose injection, it is characterized in that Navoban (Soz) injection is the aseptic parenteral solution be made up of following composition:
Fructose injection is the aseptic parenteral solution be made up of following composition:
Fructose 50g 100g
Water for injection adds to 1000ml and adds to 1000ml.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201310332615.XA CN103385883B (en) | 2013-08-02 | 2013-08-02 | Pharmaceutical composition containing tropisetron hydrochloride and fructose |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201310332615.XA CN103385883B (en) | 2013-08-02 | 2013-08-02 | Pharmaceutical composition containing tropisetron hydrochloride and fructose |
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| Publication Number | Publication Date |
|---|---|
| CN103385883A CN103385883A (en) | 2013-11-13 |
| CN103385883B true CN103385883B (en) | 2015-05-27 |
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| CN201310332615.XA Expired - Fee Related CN103385883B (en) | 2013-08-02 | 2013-08-02 | Pharmaceutical composition containing tropisetron hydrochloride and fructose |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN104825485A (en) * | 2015-05-12 | 2015-08-12 | 海南灵康制药有限公司 | Tropisetron hydrochloride and fructose-sodium chloride containing pharmaceutical composition |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1666747A (en) * | 2004-03-09 | 2005-09-14 | 杨喜鸿 | Fructose injection of anti-tumor drug |
| CN1969847A (en) * | 2006-12-11 | 2007-05-30 | 重庆人本药物研究院 | Pharmaceutical composition |
| CN102440949A (en) * | 2010-10-09 | 2012-05-09 | 江苏正大丰海制药有限公司 | Preparation method of fructose injection |
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2013
- 2013-08-02 CN CN201310332615.XA patent/CN103385883B/en not_active Expired - Fee Related
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1666747A (en) * | 2004-03-09 | 2005-09-14 | 杨喜鸿 | Fructose injection of anti-tumor drug |
| CN1969847A (en) * | 2006-12-11 | 2007-05-30 | 重庆人本药物研究院 | Pharmaceutical composition |
| CN102440949A (en) * | 2010-10-09 | 2012-05-09 | 江苏正大丰海制药有限公司 | Preparation method of fructose injection |
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| CN103385883A (en) | 2013-11-13 |
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