CN100391447C - Freeze dried powder injection of coenzyme Q10 and its preparation process - Google Patents
Freeze dried powder injection of coenzyme Q10 and its preparation process Download PDFInfo
- Publication number
- CN100391447C CN100391447C CNB2004100159599A CN200410015959A CN100391447C CN 100391447 C CN100391447 C CN 100391447C CN B2004100159599 A CNB2004100159599 A CN B2004100159599A CN 200410015959 A CN200410015959 A CN 200410015959A CN 100391447 C CN100391447 C CN 100391447C
- Authority
- CN
- China
- Prior art keywords
- hours
- ubiquinone
- coenzyme
- solution
- injectable powder
- 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.)
- Expired - Lifetime
Links
- ACTIUHUUMQJHFO-UPTCCGCDSA-N coenzyme Q10 Chemical compound COC1=C(OC)C(=O)C(C\C=C(/C)CC\C=C(/C)CC\C=C(/C)CC\C=C(/C)CC\C=C(/C)CC\C=C(/C)CC\C=C(/C)CC\C=C(/C)CC\C=C(/C)CCC=C(C)C)=C(C)C1=O ACTIUHUUMQJHFO-UPTCCGCDSA-N 0.000 title claims abstract description 83
- 235000017471 coenzyme Q10 Nutrition 0.000 title claims abstract description 81
- ACTIUHUUMQJHFO-UHFFFAOYSA-N Coenzym Q10 Natural products COC1=C(OC)C(=O)C(CC=C(C)CCC=C(C)CCC=C(C)CCC=C(C)CCC=C(C)CCC=C(C)CCC=C(C)CCC=C(C)CCC=C(C)CCC=C(C)C)=C(C)C1=O ACTIUHUUMQJHFO-UHFFFAOYSA-N 0.000 title claims abstract description 79
- 239000000843 powder Substances 0.000 title claims abstract description 42
- 229940110767 coenzyme Q10 Drugs 0.000 title claims abstract description 26
- 238000002360 preparation method Methods 0.000 title claims description 17
- 238000002347 injection Methods 0.000 title abstract description 15
- 239000007924 injection Substances 0.000 title abstract description 15
- 229920002675 Polyoxyl Polymers 0.000 claims abstract description 17
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 claims abstract description 17
- 229920000136 polysorbate Polymers 0.000 claims abstract description 15
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 13
- NPCOQXAVBJJZBQ-UHFFFAOYSA-N reduced coenzyme Q9 Natural products COC1=C(O)C(C)=C(CC=C(C)CCC=C(C)CCC=C(C)CCC=C(C)CCC=C(C)CCC=C(C)CCC=C(C)CCC=C(C)CCC=C(C)C)C(O)=C1OC NPCOQXAVBJJZBQ-UHFFFAOYSA-N 0.000 claims description 53
- 229940035936 ubiquinone Drugs 0.000 claims description 53
- 239000000243 solution Substances 0.000 claims description 35
- 238000003756 stirring Methods 0.000 claims description 27
- 238000001035 drying Methods 0.000 claims description 21
- 238000004108 freeze drying Methods 0.000 claims description 19
- 238000001914 filtration Methods 0.000 claims description 14
- 238000000859 sublimation Methods 0.000 claims description 10
- 230000008022 sublimation Effects 0.000 claims description 10
- 239000008215 water for injection Substances 0.000 claims description 9
- 239000012982 microporous membrane Substances 0.000 claims description 8
- 238000002156 mixing Methods 0.000 claims description 8
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 8
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical group OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 claims description 5
- 229930195725 Mannitol Natural products 0.000 claims description 5
- 239000000594 mannitol Substances 0.000 claims description 5
- 235000010355 mannitol Nutrition 0.000 claims description 5
- 238000010257 thawing Methods 0.000 claims description 5
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 claims description 4
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 claims description 2
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 claims description 2
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 claims description 2
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 claims description 2
- TVXBFESIOXBWNM-UHFFFAOYSA-N Xylitol Natural products OCCC(O)C(O)C(O)CCO TVXBFESIOXBWNM-UHFFFAOYSA-N 0.000 claims description 2
- 239000008101 lactose Substances 0.000 claims description 2
- HEBKCHPVOIAQTA-UHFFFAOYSA-N meso ribitol Natural products OCC(O)C(O)C(O)CO HEBKCHPVOIAQTA-UHFFFAOYSA-N 0.000 claims description 2
- 239000011780 sodium chloride Substances 0.000 claims description 2
- 239000000600 sorbitol Substances 0.000 claims description 2
- 150000003669 ubiquinones Chemical class 0.000 claims description 2
- 239000000811 xylitol Substances 0.000 claims description 2
- 235000010447 xylitol Nutrition 0.000 claims description 2
- HEBKCHPVOIAQTA-SCDXWVJYSA-N xylitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)CO HEBKCHPVOIAQTA-SCDXWVJYSA-N 0.000 claims description 2
- 229960002675 xylitol Drugs 0.000 claims description 2
- 239000003814 drug Substances 0.000 abstract description 11
- 239000000203 mixture Substances 0.000 abstract description 7
- 239000004094 surface-active agent Substances 0.000 abstract description 5
- 238000010579 first pass effect Methods 0.000 abstract description 4
- 229940079593 drug Drugs 0.000 description 7
- 230000000694 effects Effects 0.000 description 7
- 238000002474 experimental method Methods 0.000 description 6
- 239000007788 liquid Substances 0.000 description 6
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 4
- 229920000053 polysorbate 80 Polymers 0.000 description 4
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 3
- 238000000034 method Methods 0.000 description 3
- 239000001301 oxygen Substances 0.000 description 3
- 229910052760 oxygen Inorganic materials 0.000 description 3
- 206010002198 Anaphylactic reaction Diseases 0.000 description 2
- 238000010521 absorption reaction Methods 0.000 description 2
- 208000003455 anaphylaxis Diseases 0.000 description 2
- 239000002775 capsule Substances 0.000 description 2
- 210000004027 cell Anatomy 0.000 description 2
- 239000002552 dosage form Substances 0.000 description 2
- 235000021472 generally recognized as safe Nutrition 0.000 description 2
- 210000002216 heart Anatomy 0.000 description 2
- 210000003470 mitochondria Anatomy 0.000 description 2
- 239000008194 pharmaceutical composition Substances 0.000 description 2
- 108090000623 proteins and genes Proteins 0.000 description 2
- 102000004169 proteins and genes Human genes 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- 108090000312 Calcium Channels Proteins 0.000 description 1
- 102000003922 Calcium Channels Human genes 0.000 description 1
- 102000018832 Cytochromes Human genes 0.000 description 1
- 108010052832 Cytochromes Proteins 0.000 description 1
- 101710088194 Dehydrogenase Proteins 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 206010018910 Haemolysis Diseases 0.000 description 1
- 206010019280 Heart failures Diseases 0.000 description 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 230000036783 anaphylactic response Effects 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 230000006793 arrhythmia Effects 0.000 description 1
- 206010003119 arrhythmia Diseases 0.000 description 1
- 210000004204 blood vessel Anatomy 0.000 description 1
- 239000003054 catalyst Substances 0.000 description 1
- 210000000170 cell membrane Anatomy 0.000 description 1
- 230000004098 cellular respiration Effects 0.000 description 1
- 238000005352 clarification Methods 0.000 description 1
- 210000000805 cytoplasm Anatomy 0.000 description 1
- 230000002526 effect on cardiovascular system Effects 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 230000008588 hemolysis Effects 0.000 description 1
- 230000002949 hemolytic effect Effects 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 238000005286 illumination Methods 0.000 description 1
- 230000003834 intracellular effect Effects 0.000 description 1
- 238000010253 intravenous injection Methods 0.000 description 1
- 230000007794 irritation Effects 0.000 description 1
- 208000028867 ischemia Diseases 0.000 description 1
- 230000000302 ischemic effect Effects 0.000 description 1
- 230000003859 lipid peroxidation Effects 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 239000004531 microgranule Substances 0.000 description 1
- 210000003205 muscle Anatomy 0.000 description 1
- 230000002107 myocardial effect Effects 0.000 description 1
- 208000031225 myocardial ischemia Diseases 0.000 description 1
- 239000002736 nonionic surfactant Substances 0.000 description 1
- 210000000496 pancreas Anatomy 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- 150000004053 quinones Chemical class 0.000 description 1
- 125000004151 quinonyl group Chemical group 0.000 description 1
- 150000003254 radicals Chemical class 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 230000035806 respiratory chain Effects 0.000 description 1
- 238000005070 sampling Methods 0.000 description 1
- 125000002730 succinyl group Chemical group C(CCC(=O)*)(=O)* 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 239000011782 vitamin Substances 0.000 description 1
- 229940088594 vitamin Drugs 0.000 description 1
- 229930003231 vitamin Natural products 0.000 description 1
- 235000013343 vitamin Nutrition 0.000 description 1
Landscapes
- Medicinal Preparation (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Abstract
The present invention relates to a freeze-dried powder injection containing coenzyme Q10, which is used for injection. The freeze-dried powder injection comprises coenzyme Q10 and a surface active agent, wherein the surface active agent is the mixture of tween and polyoxyl stearate; the active component of the medicine is coenzyme Q10. The weight ratio of the coenzyme Q10 to the tween is 1:1 to 1:50. The weight ratio of the coenzyme Q10 to the polyoxyl stearate is 1:1 to 1:50. The present invention has the advantages that the freeze-dried powder injection containing coenzyme Q10 of is directly injected into a human body without the first-pass effect, the bioavailability is improved, and problems of the instability of instability and poor coenzyme Q10 solubility of the ordinary small water needle are solved.
Description
Technical field
The present invention relates to field of medicaments, relate in particular to a kind of ubiquinone that contains of injection
10Lyophilized injectable powder and preparation method thereof.
Background technology
Ubiquinone
10(molecular formula is C
59H
90O
4) be the fat-soluble quinones that a class and vitamins have common trait.Ubiquinone
10In respiratory chain, work passing the hydrogen carrier effect, many enzymes are all had activation.Ubiquinone
10At the intravital total content of people is 0.5mg-1.5mg, and the level in heart, liver and pancreas is higher relatively, and in intracellular distribution with mitochondrion at most (45%-50%), minimum in cytoplasm (5%-10%).
The endogenous ubiquinone
10The function that conjugated protein source is arranged has been found three kinds of ubiquinones at present
10Conjugated protein: QPs, QPc and QPn.The effect that in the Cellular respiration chain, has direct adjusting succinyl and NA-DH dehydrogenase; In addition, regulating cytochrome b-C as catalyst
1Play an important role in the complex.
Clinical research is found, exogenous ubiquinone
10Antioxidation and cell membrane stability effect are arranged, the stability of cell internal and external environment is maintained; Also can remove the free radical that lipid peroxidation produces, the pharmacological actions such as integrity of myocardial cell calcium channel when the prevention myocardial ischemia causes the mitochondrion distortion and keeps ischemia.Current, existing abroad ubiquinone
10Be widely used in ischemic heart desease, heart failure, arrhythmia and some cardiovascular illness have obtained comparatively ideal effect.
At present, the ubiquinone that goes on the market both at home and abroad
10Dosage form is a lot, and peroral dosage form tablet and capsule are arranged, the little liquid drugs injection of injection etc.Owing to all first pass effect will be arranged after tablet and the capsule oral administration, so its bioavailability is low.The little liquid drugs injection that has wherein gone on the market is made the surfactant solubilising with tween 80, but because ubiquinone
10Be fat-soluble medicine, and ubiquinone
10There is quinonyl in the structure, quite responsive to light and oxygen, so its stability is not fine, places little liquid drugs injection for a long time and can become muddy even precipitate occur, and at the aqueous solution state ubiquinone
10Easier in the degraded of light and oxygen, thus the quality of product influenced, bring certain hidden danger to clinical practice." contain ubiquinone as Chinese patent CN 1226823 is disclosed
10Pharmaceutical composition " a kind of ubiquinone that contains is provided
10As the pharmaceutical composition of active ingredient, promote oral back ubiquinone
10Absorption; Disclosed " the ubiquinone of Japan Patent JP59148718
10Composition " for obtaining good oral absorption and effect, adopt lyophilization to be made into microgranule, but can not avoid the first pass effect after oral.
Therefore, this area is starved of a kind ofly has good quality stability, and the little ubiquinone of side effect
10Injection.
Summary of the invention
The object of the present invention is to provide a kind of little ubiquinone of good stability and dissolubility and side effect that has
10Lyophilized injectable powder.
Another object of the present invention is to provide a kind of ubiquinone
10The preparation method of lyophilized injectable powder.
A kind of ubiquinone of the present invention
10Lyophilized injectable powder comprises ubiquinone
10And surfactant, it is characterized in that surfactant is the mixture of tween and polyoxyl stearate, wherein medicament active composition is a ubiquinone
10, ubiquinone
10With the weight ratio of tween be 1: 1～1: 50, ubiquinone
10With the weight ratio of polyoxyl stearate be 1: 1～1: 50.
Above-mentioned ubiquinone
10With the weight ratio of tween preferred 1: 3～1: 10.
Above-mentioned ubiquinone
10With the weight ratio of polyoxyl stearate preferred 1: 3～1: 10.
Ubiquinone of the present invention
10Lyophilized injectable powder can also contain medicinal freeze drying excipient; Medicinal freeze drying excipient is mannitol, lactose, sodium chloride, sorbitol, xylitol.
Above-mentioned ubiquinone
10With the weight ratio of medicinal freeze drying excipient be 1: 5～1: 500, preferred 1: 10～1: 50.
The invention also discloses the preparation method of above-mentioned coenzyme Q10 lyophilized injectable powder, comprise the steps:
(1), in proportion tween and polyoxyl stearate are mixed, with 50 ℃～100 ℃ water-baths thawings, stir into homogeneous state;
(2), continue in temperature is 50 ℃～100 ℃ water-bath, to add coenzyme Q10 in proportion, stirring and evenly mixing adds proper amount of water for injection again, stirring and dissolving obtains clear and bright solution;
(3), with the solution filtering with microporous membrane that obtains;
(4), the solution after filtering in the step (3) was placed-20 ℃～-60 ℃ following pre-freezes 2 hours～8 hours; Sublimation drying 15 hours～40 hours when temperature-5 ℃～-30 ℃ then; Temperature is risen to 0 ℃～25 ℃ again and carry out drying again, the time is 10 hours～40 hours;
(5), after lyophilizing finishes, seal, obtain the coenzyme Q10 lyophilized injectable powder.
After obtaining clear and bright solution in the above-mentioned step (2), can add medicinal freeze drying excipient and stirring and dissolving in proportion to clear and bright solution.
As preferably, cryodesiccated condition control in the step (4): with solution in-30 ℃～-40 ℃ following pre-freezes 4 hours～5 hours; Sublimation drying 25 hours～30 hours when temperature-10 ℃～-15 ℃ then; Temperature is risen to 10 ℃～15 ℃ again and carry out drying again, the time is 20 hours～25 hours.Need lucifuge in the above-mentioned whole process.
As a concrete technical scheme, the preparation method of coenzyme Q10 lyophilized injectable powder is as follows:
(1), the polyoxyl stearate of getting the tween of 25mg and 25mg mixes, and with 70 ℃～80 ℃ water-baths thawings, stirs into homogeneous state;
(2), continue in temperature is 70 ℃～80 ℃ water-bath, to add the 5mg coenzyme Q10, stirring and evenly mixing adds the water for injection of 2ml again, stirring and dissolving obtains clear and bright solution;
(3), with the solution that obtains filtering with microporous membrane with 0.22 μ m;
(4), place freezer dryer to carry out lyophilization the solution after filtering in the step (3), during lyophilization, at first with solution in-30 ℃ of following pre-freezes 4 hours, then temperature-10 ℃ sublimation drying 25 hours; Temperature is risen to 10 ℃ again and carry out drying again, the time is 20 hours;
(5), after lyophilizing finishes, seal, obtain the coenzyme Q10 lyophilized injectable powder.
As another concrete technical scheme, the preparation method of coenzyme Q10 lyophilized injectable powder is as follows:
(1), the polyoxyl stearate of getting the tween of 15mg and 30mg mixes, and with 50 ℃～100 ℃ water-baths thawings, stirs into homogeneous state;
(2), continue in temperature is 50 ℃～100 ℃ water-bath, to add the 5mg coenzyme Q10, stirring and evenly mixing adds the water for injection of 2ml again, stirring and dissolving obtains clear and bright solution, adds 50mg mannitol, stirring and dissolving is clear and bright to solution;
(3), with the solution that obtains filtering with microporous membrane with 0.22 μ m;
(4), place freezer dryer to carry out lyophilization the solution after filtering in the step (3), during lyophilization, at first with solution in-40 ℃ of following pre-freezes 5 hours, then temperature-15 ℃ sublimation drying 30 hours; Temperature is risen to 15 ℃ again and carry out drying again, the time is 25 hours;
(5), after lyophilizing finishes, seal, obtain the coenzyme Q10 lyophilized injectable powder.
Ubiquinone of the present invention
10The specification of lyophilized injectable powder is (with ubiquinone
10The weight meter) is 0.5mg-50mg, is preferably 2mg-10mg.Characteristics of the present invention are to adopt blended nonionic surfactant to do solubilizing agent, promptly adopt tween and polyoxyl stearate to mix according to a certain percentage and do solubilizing agent, the preferred tween 80 of tween wherein, and the ubiquinone made from freeze-dry process
10Freeze-dried composition.Wherein polyoxyl stearate records in Chinese Pharmacopoeia, American Pharmacopeia and Japanese Pharmacopoeia, in the attached volume of American Pharmacopeia and Japanese Pharmacopoeia---and state decides formulary publications such as (National Formulary) and has all offered some clarification on, and its toxicity is extremely low.
Ubiquinone of the present invention
10Lyophilized injectable powder is applicable to clinically and uses.Before use, earlier with melting freeze-dried powder in 50 ℃～100 ℃ water-baths, add the water for injection dissolving of 2ml again, muscle or intravenous injection then.Ubiquinone of the present invention
10Lyophilized injectable powder directly adopts and is injected into human body, and no first pass effect has improved bioavailability; The unstability and the ubiquinone of common little liquid drugs injection have been solved
10Poorly soluble problem.
The specific embodiment
The present invention is further illustrated below by several specific embodiments, but the present invention is not limited by embodiment.
Embodiment 1: get the polyoxyl stearate of 25mg and the tween 80 of 25mg and mix, melt in 70 ℃～80 ℃ water-bath, stir and make into homogeneous state.Continuation water-bath in 70 ℃～80 ℃ warm water, lucifuge (following whole operation process needs lucifuge), the ubiquinone of adding 5mg
10, mixing adds the water for injection of 2ml again, stirring and dissolving, and solution is clear and bright, with the filtering with microporous membrane of 0.22 μ m, places freezer dryer to carry out lyophilization then.Wherein cryodesiccated condition is controlled to be in freezer dryer: with solution in-30 ℃ of following pre-freezes 4 hours; Then temperature-10 ℃ sublimation drying 25 hours; Temperature is risen to 10 ℃ again and carry out drying again, the time is 20 hours, seals at last, gets orange-yellow ubiquinone
10Lyophilized injectable powder.
Embodiment 2: get the polyoxyl stearate of 30mg and the tween 80 of 15mg and mix, melt 50 ℃～100 ℃ water-baths, stir and make into homogeneous state.Continuation water-bath in 50 ℃～100 ℃ warm water, lucifuge (following whole operation process needs lucifuge), the ubiquinone of adding 5mg
10, mixing adds the water for injection of 2ml again, stirring and dissolving, and solution is clear and bright, adds 50mg mannitol at last, stirring and dissolving, the filtering with microporous membrane of the clear and bright usefulness 0.22 μ m of solution places freezer dryer to carry out lyophilization then.Wherein cryodesiccated condition is controlled to be in freezer dryer: with solution in-40 ℃ of following pre-freezes 5 hours; Then temperature-15 ℃ sublimation drying 30 hours; Temperature is risen to 15 ℃ again and carry out drying again, the time is 25 hours, seals at last, gets orange-yellow ubiquinone
10Lyophilized injectable powder.
Experimental example 1: ubiquinone
10The stability of freeze-dried powder.
The ubiquinone that embodiment 1 is made
10Freeze-dried powder and conventional little liquid drugs injection carry out study on the stability, and the influence factor adopts under the 4500LX illumination and placed 10 days, towards the oxygen fill, placed 10 days for 30 ℃, and respectively the 5th day and the tenth day sampling and measuring, result such as table 1.
Table 1
Above result shows: ubiquinone of the present invention
10Freeze-dried powder can be rebuild the injection that obtains clear rapidly after adding water.Under identical experiment condition, the quality stability of injectable powder obviously is better than little liquid drugs injection.This fine solubility and quality stability had both guaranteed the safety of medication, had also prolonged ubiquinone
10Effect duration.
Experimental example 2: ubiquinone
10The Generally Recognized as safe experiment of freeze-dried powder.
The ubiquinone that embodiment 1 is made
10Freeze-dried powder is done the Generally Recognized as safe experiment, comprises hemolytic experiment, blood vessel irritation experiment and anaphylaxis experiment, and experimental result shows ubiquinone of the present invention
10Freeze-dried powder nonirritant, no anaphylactic reaction do not have haemolysis yet.
Claims (10)
1. the preparation method of a coenzyme Q10 lyophilized injectable powder is characterized in that comprising the steps:
(1) in proportion tween and polyoxyl stearate are mixed, melt, stir into homogeneous state with 50 ℃～100 ℃ water-baths;
(2) continue to add coenzyme Q10 in proportion in temperature is 50 ℃～100 ℃ water-bath, stirring and evenly mixing adds proper amount of water for injection again, and stirring and dissolving obtains clear and bright solution;
(3) with the solution filtering with microporous membrane that obtains;
(4) solution after filtering in the step (3) was placed-20 ℃～-60 ℃ following pre-freezes 2 hours～8 hours; Sublimation drying 15 hours～40 hours when temperature-5 ℃～-30 ℃ then; Temperature is risen to 0 ℃～25 ℃ again and carry out drying again, the time is 10 hours～40 hours;
(5) after lyophilizing is finished, seal, obtain the coenzyme Q10 lyophilized injectable powder;
The above-mentioned coenzyme Q10 and the weight ratio of tween are 1: 1～1: 50, and the weight ratio of coenzyme Q10 and polyoxyl stearate is 1: 1～1: 50.
2. the preparation method of a kind of coenzyme Q10 lyophilized injectable powder according to claim 1 after it is characterized in that obtaining clear and bright solution in the step (2), adds medicinal freeze drying excipient and stirring and dissolving in proportion to clear and bright solution.
3. a kind of ubiquinone according to claim 2
10The preparation method of lyophilized injectable powder is characterized in that medicinal freeze drying excipient is mannitol, lactose, sodium chloride, sorbitol, xylitol.
4. according to claim 2 or 3 described a kind of ubiquinones
10The preparation method of lyophilized injectable powder is characterized in that ubiquinone
10With the weight ratio of medicinal freeze drying excipient be 1: 5～1: 500.
5. according to the described a kind of ubiquinone of claim 4
10The preparation method of lyophilized injectable powder is characterized in that ubiquinone
10With the weight ratio of medicinal freeze drying excipient be 1: 10～1: 50.
6. the preparation method of a kind of coenzyme Q10 lyophilized injectable powder according to claim 1 and 2 is characterized in that cryodesiccated condition control in the step (4): with solution in-30 ℃～-40 ℃ following pre-freezes 4 hours～5 hours; Sublimation drying 25 hours～30 hours when temperature-10 ℃～-15 ℃ then; Temperature is risen to 10 ℃～15 ℃ again and carry out drying again, the time is 20 hours～25 hours.
7. a kind of ubiquinone according to claim 1
10The preparation method of lyophilized injectable powder is characterized in that ubiquinone
10With the weight ratio of tween be 1: 3～1: 10.
8. a kind of ubiquinone according to claim 1
10The preparation method of lyophilized injectable powder is characterized in that ubiquinone
10With the weight ratio of polyoxyl stearate be 1: 3～1: 10.
9. the preparation method of a kind of coenzyme Q10 lyophilized injectable powder according to claim 1 is characterized in that:
(1), the polyoxyl stearate of getting the tween of 25mg and 25mg mixes, and with 70 ℃～80 ℃ water-baths thawings, stirs into homogeneous state;
(2), continue in temperature is 70 ℃～80 ℃ water-bath, to add the 5mg ubiquinone
10, stirring and evenly mixing adds the water for injection of 2ml again, and stirring and dissolving obtains clear and bright solution;
(3) with the solution that obtains filtering with microporous membrane with 0.22 μ m;
(4), place freezer dryer to carry out lyophilization the solution after filtering in the step (3), during lyophilization, at first with solution in-30 ℃ of following pre-freezes 4 hours, then temperature-10 ℃ sublimation drying 25 hours; Temperature is risen to 10 ℃ again and carry out drying again, the time is 20 hours;
(5), after lyophilizing finishes, seal, obtain ubiquinone
10Lyophilized injectable powder.
10. the preparation method of a kind of coenzyme Q10 lyophilized injectable powder according to claim 1 is characterized in that:
(1), the polyoxyl stearate of getting the tween of 15mg and 30mg mixes, and with 50 ℃～100 ℃ water-baths thawings, stirs into homogeneous state;
(2), continue in temperature is 50 ℃～100 ℃ water-bath, to add the 5mg ubiquinone
10, stirring and evenly mixing adds the water for injection of 2ml again, and stirring and dissolving obtains clear and bright solution, adds 50mg mannitol, and stirring and dissolving is clear and bright to solution;
(3) with the solution that obtains filtering with microporous membrane with 0.22 μ m;
(4), place freezer dryer to carry out lyophilization the solution after filtering in the step (3), during lyophilization, at first with solution in-40 ℃ of following pre-freezes 5 hours, then temperature-15 ℃ sublimation drying 30 hours; Temperature is risen to 15 ℃ again and carry out drying again, the time is 25 hours;
(5), after lyophilizing finishes, seal, obtain ubiquinone
10Lyophilized injectable powder.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB2004100159599A CN100391447C (en) | 2004-01-15 | 2004-01-15 | Freeze dried powder injection of coenzyme Q10 and its preparation process |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB2004100159599A CN100391447C (en) | 2004-01-15 | 2004-01-15 | Freeze dried powder injection of coenzyme Q10 and its preparation process |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN1593392A CN1593392A (en) | 2005-03-16 |
| CN100391447C true CN100391447C (en) | 2008-06-04 |
Family
ID=34663038
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CNB2004100159599A Expired - Lifetime CN100391447C (en) | 2004-01-15 | 2004-01-15 | Freeze dried powder injection of coenzyme Q10 and its preparation process |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN100391447C (en) |
Families Citing this family (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101066260B (en) * | 2006-11-17 | 2012-11-07 | 姚瑶 | Coenzyme Q10 emulsion and its freeze dried emulsion and their preparation process |
| CN103191431B (en) * | 2013-04-03 | 2015-07-01 | 郑云 | Coenzyme Q10 sodium chloride injection uneasy to crystallize and preparation method thereof |
| CN105380809A (en) * | 2015-11-25 | 2016-03-09 | 陕西艾美雅生物科技有限公司 | Preparation method of solid cosmetic matrix and solid cosmetic matrix |
| CN105380808A (en) * | 2015-11-25 | 2016-03-09 | 陕西艾美雅生物科技有限公司 | Cosmetic substrate, and preparation method and using method thereof |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4491594A (en) * | 1983-03-08 | 1985-01-01 | Eisai Co., Ltd. | Method for treatment of seizures |
| CN86100582A (en) * | 1986-05-21 | 1987-12-02 | 泰州生物化学制药厂 | A kind of coenzyme Q 10 injection that makes keeps clear and bright method |
| CN1226823A (en) * | 1996-08-16 | 1999-08-25 | 钟渊化学工业株式会社 | Pharmaceutical composition comprising coenzyme Q10 |
-
2004
- 2004-01-15 CN CNB2004100159599A patent/CN100391447C/en not_active Expired - Lifetime
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4491594A (en) * | 1983-03-08 | 1985-01-01 | Eisai Co., Ltd. | Method for treatment of seizures |
| CN86100582A (en) * | 1986-05-21 | 1987-12-02 | 泰州生物化学制药厂 | A kind of coenzyme Q 10 injection that makes keeps clear and bright method |
| CN1226823A (en) * | 1996-08-16 | 1999-08-25 | 钟渊化学工业株式会社 | Pharmaceutical composition comprising coenzyme Q10 |
Also Published As
| Publication number | Publication date |
|---|---|
| CN1593392A (en) | 2005-03-16 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CA3149460A1 (en) | Drug composition containing abiraterone acetate, and preparation method therefor and application thereof | |
| CA2805031A1 (en) | Compositions and methods for modulating the pharmacokinetics and pharmacodynamics of insulin | |
| EP3505161A1 (en) | Sublingual pharmaceutical composition of edaravone and (+)-2-borneol | |
| JPS6354319A (en) | Release controlled carbidopa/levodopa blend | |
| Sasahara et al. | Dosage form design for improvement of bioavailability of levodopa II: bioavailability of marketed levodopa preparations in dogs and parkinsonian patients | |
| CN102481288B (en) | Pharmaceutical composition of temozolomide comprising amino acid stabilizer and preparation method thereof | |
| CN100391447C (en) | Freeze dried powder injection of coenzyme Q10 and its preparation process | |
| US5624682A (en) | Pharmaceutical formulations based on a ketoprofen solution in soft capsules, and processes for their preparation | |
| EP3821920A1 (en) | Combination for endoscopic surgery | |
| CN104800172A (en) | Carbazochrome sodium sulfonate powder injection for injection and preparation method thereof | |
| CN111529494B (en) | Oryzanol micelle compound solid dispersion and preparation method thereof | |
| JP2001240558A (en) | Solid preparation containing polyvalent-unsaturated fatty acid as transmucosal absorption promoter | |
| CN1895230A (en) | Lisinopril drop balls and production thereof | |
| JP2007326796A (en) | Bleaching agent containing gold colloid and thyrosinase inhibitor | |
| JP2020533318A (en) | Pharmaceutical composition and preparation method of docetaxel conjugate | |
| CN103385851B (en) | For anticancer injectable pharmaceutical composition | |
| CN109381466A (en) | Promote the therapeutic agent of diabetic wound healing | |
| KR100679925B1 (en) | Novel composite of rectal suppository containing 5-fluorouracil | |
| Goel et al. | Pharmaceutical excipients | |
| KR0171693B1 (en) | Composition for the contents of gliclazide containing soft capsule | |
| JPH0474123A (en) | Stable activated vitamin d3 preparation | |
| CN101468028A (en) | Pharmaceutical composition containing gliclazide | |
| KR100299942B1 (en) | Biphenyl Dimethyl Dicarboxylate Liquid | |
| JPH083031A (en) | Sustained release pharmaceutical preparation containing sparingly water-soluble medicine | |
| KR20240080282A (en) | A sustained-release preparation containing Dutasteride and a method for manufacturing the same |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C14 | Grant of patent or utility model | ||
| GR01 | Patent grant | ||
| ASS | Succession or assignment of patent right |
Owner name: ZHEJIANG RUIDA PHARMACEUTICAL CO., LTD. HANGZHOU S Owner name: HAINAN POLY PHARMACEUTICAL CO., LTD. Free format text: FORMER OWNER: FAN MINHUA Effective date: 20100707 |
|
| C41 | Transfer of patent application or patent right or utility model | ||
| COR | Change of bibliographic data |
Free format text: CORRECT: ADDRESS; FROM: 310004 HOUSE 5, BUILDING 9, NO.167, HUANCHENG NORTH ROAD, HANGZHOU CITY, ZHEJIANG PROVINCE TO: 571127 GUILINYANG ECONOMIC AND TECHNOLOGICAL DEVELOPMENT ZONE, MEILAN DISTRICT, HAIKOU CITY, HAINAN PROVINCE |
|
| TR01 | Transfer of patent right |
Effective date of registration: 20100707 Address after: 571127 Guilin economic and Technological Development Zone, Meilan District, Hainan, Haikou Co-patentee after: Zhejiang Ruida Pharmaceutical Co.,Ltd. Patentee after: Hainan Poly Pharm Co.,Ltd. Co-patentee after: HANGZHOU SHARPLY PHARM R&D INSTIT. Co.,Ltd. Address before: 5, building 9, building 167, building 310004, Ring North Road, Hangzhou, Zhejiang Patentee before: Fan Minhua |
|
| CI01 | Publication of corrected invention patent application |
Correction item: Patentee Correct: Zhejiang Ridae Pharmaceutical Co., Ltd. False: Zhejiang Ruida Pharmaceutical Co., Ltd. Number: 33 Volume: 26 |
|
| CI03 | Correction of invention patent |
Correction item: Patentee Correct: Zhejiang Ridae Pharmaceutical Co., Ltd. False: Zhejiang Ruida Pharmaceutical Co., Ltd. Number: 33 Page: The title page Volume: 26 |
|
| C56 | Change in the name or address of the patentee |
Owner name: HAINAN PLOY PHARMACEUTICAL CO., LTD. Free format text: FORMER NAME: HAINAN PULIN PHARMACEUTICAL CO., LTD. |
|
| CP01 | Change in the name or title of a patent holder |
Address after: 571127 Guilin economic and Technological Development Zone, Meilan District, Hainan, Haikou Patentee after: HAINAN POLY PHARM. Co.,Ltd. Patentee after: ZHEJIANG POLY PHARMACEUTICAL Co.,Ltd. Patentee after: HANGZHOU SHARPLY PHARM R&D INSTIT. Co.,Ltd. Address before: 571127 Guilin economic and Technological Development Zone, Meilan District, Hainan, Haikou Patentee before: Hainan Poly Pharm Co.,Ltd. Patentee before: Zhejiang Ruida Pharm Co.,Ltd. Patentee before: HANGZHOU SHARPLY PHARM R&D INSTIT. Co.,Ltd. |
|
| CX01 | Expiry of patent term | ||
| CX01 | Expiry of patent term |
Granted publication date: 20080604 |