CN103393593A - Pharmaceutical composition containing ambroxol hydrochloride and fructose - Google Patents
Pharmaceutical composition containing ambroxol hydrochloride and fructose Download PDFInfo
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- CN103393593A CN103393593A CN2013103326183A CN201310332618A CN103393593A CN 103393593 A CN103393593 A CN 103393593A CN 2013103326183 A CN2013103326183 A CN 2013103326183A CN 201310332618 A CN201310332618 A CN 201310332618A CN 103393593 A CN103393593 A CN 103393593A
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Abstract
The invention relates to a pharmaceutical composition containing an ambroxol hydrochloride injection preparation and a fructose injection liquid, and particularly relates to a combined application package comprising the ambroxol hydrochloride injection preparation and the fructose injection liquid. When the combined application package is in use, the ambroxol hydrochloride injection preparation and the fructose injection liquid are mixed for intravenous drip. The pharmaceutical composition has the effect for eliminating phlegm and excreting the phlegm and can supplement energy and body fluid for the human body.
Description
Technical field
The present invention relates to a kind of pharmaceutical composition that comprises ambroxol hydrochloride and fructose, be specifically related to a kind of applied in any combination packing that is formed by ambroxol hydrochloride injection and fructose injection, belong to medical technical field.
Background technology
Ambroxol hydrochloride has the characteristic that mucus is got rid of facilitation and dissolved secretions.Can promote the eliminating of thick secretions in respiratory tract and the delay of minimizing mucus, because significantly promote expectoration, improve breath state.During the application ambroxol hydrochloride therapy, the secretion of patient's mucus can return to normal condition.Cough and amount of expectoration usually significantly reduce, the surfactant of respiratory mucosa thereby bring into play its normal defencive function.The distribution of ambroxol hydrochloride from blood to tissue is fast and significantly, lungs are main target organ.Plasma half-life is 7-12 hour, there is no accumulative effect.Ambroxol hydrochloride is mainly at liver metabolism, and about 90% is removed by kidney.Ambroxol hydrochloride is applicable to acute, the chronic lung disease of and expectoration dysfunction undesired with the sputum secretion, for example treatment of eliminating the phlegm of chronic bronchitis acute exacerbation, asthmatic bronchitis and bronchial asthma; The prophylactic treatment of pulmonary complication after operation; The treatment of premature infant and neonatal infant respiratory distress syndrome (IRDS).
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, mainly at liver, passes through the fructokinase metabolism, and being easy to metabolism is fruit acid, is converted into rapidly energy.The pharmacokinetics data shows, Healthy People continues input fructose can reach 6～8 mM/ls of steady plasma-drug concentration, ATP and Phos all drop to steady-state level in body, hepatic clearance be 0.53 ml/g (liver is heavy)/minute, endocellular metabolism meets the first order kinetics process.The fructose pharmacological action is basically identical with glucose, the effect of have direct heat supply, supplementing body fluid and nutrition whole body.After the fructose intravenously administrable, metabolism is but fast than glucose in vivo, easily by body, is absorbed, and does not rely on insulin, and is little to blood sugar influence, is more suitable for diabetes, hepatopathy patients supply energy, supplements body fluid.
Fructose is for keeping the skin wet under the insulin-resistant states such as postoperative infection of burning or while being not suitable for using glucose or the patient's of the energy body fluid supplement therapy.
Prior art this injection in the ambroxol hydrochloride injection operation instructions also can use with glucose, fructose, saline or ringer's solution mixed venous drop; Ambroxol Hydrochloride for Injection also available appropriate sterile water for injection dilutes rear and glucose, fructose, 0.9% sodium chloride injection or the use of ringer's solution mixed venous drop.In clinical use, need to buy respectively use in conjunction, the assembly packaging of ambroxol hydrochloride injection and fructose does not appear in the Shang He medical institutions of market.
The applicant offers medical institutions and market by ambroxol hydrochloride injection of the present invention and fructose injection with the form of assembly packaging, select ambroxol hydrochloride injection and the fructose injection of the formation of special component, not only be conducive to cough-relieving, and improved its stability and extended effective drug duration.
Summary of the invention
One of purpose of the present invention, provide the pharmaceutical composition of a kind of ambroxol-hydrochloride-containing and fructose.
One of purpose of the present invention, provide a kind of and formed pharmaceutical composition by ambroxol hydrochloride injection and fructose injection, wherein, ambroxol hydrochloride injection is the sterile freeze-drying preparation that adds the formulated aseptic parenteral solution of appropriate adjuvant or add appropriate excipient to make, and the fructose injection is the aseptic parenteral solution that adds appropriate adjuvant formulated.
One of purpose of the present invention, provide a kind of and formed the medicinal application assembly packaging by ambroxol hydrochloride injection and fructose injection, wherein, ambroxol hydrochloride injection is the sterile freeze-drying preparation that adds the formulated aseptic parenteral solution of appropriate adjuvant or add appropriate excipient to make, and the fructose injection is the aseptic parenteral solution that adds appropriate adjuvant formulated.
Applied in any combination packing provided by the invention, during use instil ambroxol hydrochloride injection and fructose injection mixed venous.
Applied in any combination packing specification provided by the invention is ambroxol hydrochloride injection 2ml:15mg or 4ml:30mg or 15mg/ bottle or 30mg/ bottle, fructose injection 250-500ml.
As the present invention's one preferred embodiment, ambroxol hydrochloride injection can be ambroxol hydrochloride injection or Ambroxol Hydrochloride for Injection lyophilized injectable powder.
Ambroxol hydrochloride injection of the present invention, wherein, ambroxol hydrochloride injection is by ambroxol hydrochloride and the formulated sterile water solution of appropriate amount of auxiliary materials; The Ambroxol Hydrochloride for Injection lyophilized injectable powder is the sterile freeze-drying preparation that adds appropriate excipient to make by ambroxol hydrochloride.
As one of specific embodiment, concrete component and consumption are as follows:
The present invention also provides a kind of preparation method of ambroxol hydrochloride injection, and concrete steps are:
(1) to the water for injection that adds total amount 80% in Agitation Tank, temperature control 70-80 ℃;
(2) add while stirring aspartic acid and the sodium hydrogen phosphate of recipe quantity, stir and make to dissolve fully;
(3) add again the sorbitol of recipe quantity, stir and make to dissolve fully;
(4) within joining the charcoal cabinet, take cumulative volume 0.05%(g/ml) injection-use activated carbon, approximately the water for injection of 50 times is by the injection-use activated carbon moistening, standby to add the charcoal amount;
(5) add the injection-use activated carbon of moistening, stirred 30 minutes;
(6) the solution coarse filtration is taken off charcoal, through 0.45 μ m cartridge filter, filters;
(7) then add the ambroxol hydrochloride of recipe quantity, stir and make it to dissolve fully;
(8) mend and add to the full amount of water for injection;
(9) detect medicinal liquid pH and should be 4.9-5.2, if any deviation, with 2mol/L aspartic acid solution or 2mol/L disodium phosphate soln, regulate;
(10) qualified to visible foreign matters with 0.22 μ m microporous filter membrane aseptic filtration, fill, inflated with nitrogen, sealing, sterilizing, obtain ambroxol hydrochloride injection; Perhaps, qualified to visible foreign matters with 0.22 μ m microporous filter membrane aseptic filtration, fill, lyophilization, obtain Ambroxol Hydrochloride for Injection.
Fructose injection of the present invention is the formulated sterile water solution of fructose.
As one of specific embodiment, concrete component and consumption are as follows:
The present invention also provides a kind of preparation method of fructose injection, and concrete steps are:
(1) dense joining: to the water for injection that adds recipe quantity 30% in dense preparing tank, the fructose that adds recipe quantity, stirring makes it to dissolve, add recipe quantity 0.1%(g/ml) moistening medicinal charcoal, stirred 30 minutes, filtering decarbonization, filter into dilute preparing tank, with water for injection, repeatedly rinse dense preparing tank, and filter into dilute preparing tank;
(2) rare joining: add to the water for injection of recipe quantity 90% in dilute preparing tank, with the 0.1mol/L hydrochloric acid solution, regulating pH value is 3.8-4.0, adds recipe quantity 0.1%(g/ml) moistening medicinal charcoal, stirred 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 μ m, fill, seal;
(4) sterilizing: 121 ℃ of pressure sterilizings 15 minutes, spraying cooling, offer for sale fast, naturally cools to room temperature.
The present invention also provides a kind of applied in any combination by ambroxol hydrochloride injection and fructose injection to be packaged in acute, chronic lung disease that and expectoration dysfunction undesired with the sputum secretion are treated in preparation, and for example chronic bronchitis acute exacerbation, asthmatic bronchitis and bronchial asthma eliminates the phlegm; The prevention of pulmonary complication after operation; Application in premature infant and neonatal infant respiratory distress syndrome (IRDS) etc.The effect that not only has the expectoration of eliminating the phlegm, and can also supplement energy and the body fluid of human body.
The specific embodiment
Embodiment 1The preparation of ambroxol hydrochloride injection
Prescription:
Preparation process:
(1) in container, add total amount 4800ml water for injection, temperature control 70-80 ℃;
(2) add while stirring 5.4g aspartic acid and 23.1g sodium hydrogen phosphate, stir and make to dissolve fully;
(3) within joining the charcoal cabinet, take the injection-use activated carbon of 3g, add the water for injection of 150ml by the injection-use activated carbon moistening, standby;
(4) add the injection-use activated carbon of moistening, stirred 30 minutes;
(5) the solution coarse filtration is taken off charcoal, through 0.45 μ m cartridge filter, filters;
(6) then add the 45g ambroxol hydrochloride, stir and make it to dissolve fully;
(7) add water for injection to 6000ml;
(8) detecting medicinal liquid pH is 5.0, does not regulate;
(9) qualified to visible foreign matters with 0.22 μ m microporous filter membrane aseptic filtration, fill, 2ml/ props up with 4ml/ and props up, inflated with nitrogen, sealing, sterilizing, obtain.
Comparative Examples 1The preparation of ambroxol hydrochloride injection
Prescription:
Preparation process is according to the technique preparation of embodiment 1.
Embodiment 2The preparation of Ambroxol Hydrochloride for Injection
Prescription:
Preparation process:
(1) in container, add total amount 4800ml water for injection, temperature control 70-80 ℃;
(2) add while stirring 5.4g aspartic acid and 23.1g sodium hydrogen phosphate, stir and make to dissolve fully;
(3) add again the 240g sorbitol, stir and make to dissolve fully;
(4) within joining the charcoal cabinet, take the injection-use activated carbon of 3g, add the water for injection of 150ml by the injection-use activated carbon moistening, standby;
(5) add the injection-use activated carbon of moistening, stirred 30 minutes;
(6) the solution coarse filtration is taken off charcoal, through 0.45 μ m cartridge filter, filters;
(7) then add the 45g ambroxol hydrochloride, stir and make it to dissolve fully;
(8) add water for injection to 6000ml;
(9) detecting medicinal liquid pH is 5.0, does not regulate;
(10) qualified to visible foreign matters with 0.22 μ m microporous filter membrane aseptic filtration, fill, 2ml/ bottle and 4ml/ bottle, lyophilization, obtain.
Comparative Examples 2The preparation of Ambroxol Hydrochloride for Injection
Prescription:
Preparation process is according to the technique preparation of embodiment 2
Embodiment 3The preparation of fructose injection
Prescription:
Preparation process:
(1) dense joining: the water for injection to adding 30L in dense preparing tank, add 10000g fructose, stir and make it to dissolve, the moistening medicinal charcoal that adds 100g, stirred filtering decarbonization 30 minutes, filter into dilute preparing tank, with water for injection, repeatedly rinse dense preparing tank, and filter into dilute preparing tank;
(2) rare joining: in dilute preparing tank, add the water for injection to 90L, with the 0.1mol/L hydrochloric acid solution, regulating pH value is 3.9, adds the moistening medicinal charcoal of 100g, stirs 30 minutes, and filtering decarbonization, add water for injection to 100L;
(3) with the microporous filter membrane fine straining of 0.22 μ m, fill, 250ml/ bottle and 500ml/ bottle, sealing;
(4) sterilizing: 121 ℃ of pressure sterilizings 15 minutes, spraying cooling, offer for sale fast, naturally cools to room temperature.
Embodiment 4The preparation of assembly packaging medicine
Combination 1: embodiment 1A preparation and embodiment 3 fructose injection 250ml.
Combination 2: embodiment 1B preparation and embodiment 3 fructose injection 500ml.
Combination 3: embodiment 2C preparation and embodiment 3 fructose injection 250ml.
Combination 4: embodiment 2D preparation and embodiment 3 fructose injection 500ml.
Combination 5: Comparative Examples 1A preparation and embodiment 3 fructose injection 250ml.
Combination 6: Comparative Examples 1B preparation and embodiment 3 fructose injection 500ml.
Combination 7: Comparative Examples 2C preparation and embodiment 3 fructose injection 250ml.
Combination 8: Comparative Examples 2D preparation and embodiment 3 fructose injection 500ml.
Test example 1 pharmacology irritant test
Get 16 of the New Zealand Journal of Health Physical Education does of body weight 2.0-2.5kg, be divided at random four groups.New zealand rabbit is placed in holder, the medicine of the first group of abdominal part hypodermic embodiment of the present invention 4 combination 1, the medicine of the second group of abdominal part hypodermic embodiment of the present invention 4 combination 5, the medicine of the 3rd group of abdominal part hypodermic embodiment of the present invention 4 combinations 3, the medicine of the 4th group of abdominal part hypodermic embodiment of the present invention 4 combinations 7, every new zealand rabbit injection 5ml, during injection and after injection, note observing injection site and have or not redness, hyperemia, the stimulation such as hemorrhage and downright bad.In the 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 the 3rd group the irritant reaction such as obvious redness, hyperemia, necrosis do not occur, and a small amount of irritant reaction such as red and swollen and downright bad appears in the new zealand rabbit injection site of second group and the 4th group.
Pathological examination: first group and the 3rd group: the skin histology structure 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.
Second group and the 4th group: epidermis thickens, and subcutaneous tissue is congested, edema, and inflammatory cell infiltration is arranged.
Conclusion: the product of particular excipient of the present invention is without the obvious stimulation effect, and zest is far smaller than prior art products.
Test example 2 pharmacodynamics tests
Get 40 rats, body weight (205 ± 10) g, be divided at random 4 groups, wherein first group of intravenous injection embodiment of the present invention 4 makes up 1 medicine, the medicine of the second group of intravenous injection embodiment of the present invention 4 combination 5, the medicine of the 3rd group of intravenous injection embodiment of the present invention 3 combinations 3, the medicine of the 4th group of intravenous injection embodiment of the present invention 4 combinations 7.After administration, 2h took a blood sample 48 hours.
Adopt high performance liquid chromatography to detect the blood drug level of ambroxol hydrochloride.Use software 3p87 and WT1.4 to carry out data analysis, relevant pharmacokinetic parameters result such as following table.
As can be seen from the above experimental data, in four assembly 5 solution, first group and the 3rd group of solution are that the sample of the embodiment of the present invention 4 combinations 1 and combination 3 is the embodiment of the present invention 4 combinations 5 than second group and the 4th group of solution and makes up 7 sample bioavailability and greatly improve, absolutely proved the intravenous benefit of assembly packaging of ambroxol hydrochloride injection of the present invention and fructose injection, make injection improve widely bioavailability, increase drug effect, obtained unexpected technical effect.
Claims (4)
1. pharmaceutical composition that comprises ambroxol hydrochloride injection and fructose injection, it is characterized in that ambroxol hydrochloride injection is the sterile freeze-drying preparation that adds the formulated aseptic parenteral solution of appropriate adjuvant or add appropriate excipient to make, fructose injection is the aseptic parenteral solution that adds appropriate adjuvant formulated.
2. pharmaceutical composition according to claim 1, the specification that it is characterized in that ambroxol hydrochloride injection is 2ml:15mg or 4ml:30mg or 15mg/ bottle or 30mg/ bottle; The specification of fructose injection is 250-500ml.
3. pharmaceutical composition according to claim 1 and 2, is characterized in that ambroxol hydrochloride injection is selected from ambroxol hydrochloride injection or Ambroxol Hydrochloride for Injection lyophilized injectable powder; Described fructose injection is the formulated sterile water solution of fructose.
4. pharmaceutical composition according to claim 1, is characterized in that this pharmaceutical composition can pack for applied in any combination.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201310332618.3A CN103393593B (en) | 2013-08-02 | 2013-08-02 | Pharmaceutical composition containing ambroxol hydrochloride and fructose |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201310332618.3A CN103393593B (en) | 2013-08-02 | 2013-08-02 | Pharmaceutical composition containing ambroxol hydrochloride and fructose |
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| Publication Number | Publication Date |
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| CN103393593A true CN103393593A (en) | 2013-11-20 |
| CN103393593B CN103393593B (en) | 2014-09-10 |
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| Application Number | Title | Priority Date | Filing Date |
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| CN201310332618.3A Expired - Fee Related CN103393593B (en) | 2013-08-02 | 2013-08-02 | Pharmaceutical composition containing ambroxol hydrochloride and fructose |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104887622A (en) * | 2015-06-08 | 2015-09-09 | 安徽双鹤药业有限责任公司 | Stable ambroxol hydrochloride huge capacity injection and preparation method thereof |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1954808A (en) * | 2005-10-27 | 2007-05-02 | 常州市第四制药厂有限公司 | High dose Ambroxol hydrochloride freeze-dried preparation and preparation method |
| CN101416956A (en) * | 2007-10-22 | 2009-04-29 | 天津康鸿医药科技发展有限公司 | Ambroxol hydrochloride injection |
-
2013
- 2013-08-02 CN CN201310332618.3A patent/CN103393593B/en not_active Expired - Fee Related
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1954808A (en) * | 2005-10-27 | 2007-05-02 | 常州市第四制药厂有限公司 | High dose Ambroxol hydrochloride freeze-dried preparation and preparation method |
| CN101416956A (en) * | 2007-10-22 | 2009-04-29 | 天津康鸿医药科技发展有限公司 | Ambroxol hydrochloride injection |
Non-Patent Citations (2)
| Title |
|---|
| 叶华等: "盐酸氨溴索注射液在果糖注射液中的配伍稳定性研究", 《中国现代应用药学》, vol. 27, no. 5, 31 May 2010 (2010-05-31), pages 468 - 470 * |
| 潘力等: "注射用盐酸氨溴索与5种注射液的配伍稳定性考察", 《中国医药导刊》, vol. 14, no. 6, 31 December 2012 (2012-12-31), pages 1098 - 1099 * |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104887622A (en) * | 2015-06-08 | 2015-09-09 | 安徽双鹤药业有限责任公司 | Stable ambroxol hydrochloride huge capacity injection and preparation method thereof |
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| CN103393593B (en) | 2014-09-10 |
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Granted publication date: 20140910 Termination date: 20170802 |