CN102552923A - Pharmaceutical composition containing L-carnitine and coenzyme Q10 as well as its preparation method - Google Patents
Pharmaceutical composition containing L-carnitine and coenzyme Q10 as well as its preparation method Download PDFInfo
- Publication number
- CN102552923A CN102552923A CN2012100257327A CN201210025732A CN102552923A CN 102552923 A CN102552923 A CN 102552923A CN 2012100257327 A CN2012100257327 A CN 2012100257327A CN 201210025732 A CN201210025732 A CN 201210025732A CN 102552923 A CN102552923 A CN 102552923A
- Authority
- CN
- China
- Prior art keywords
- pharmaceutical composition
- salt
- acid
- pharmaceutically acceptable
- ester
- 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
Abstract
The present invention provides a pharmaceutical composition containing L-carnitine and coenzyme Q10 as well as its preparation method. The pharmaceutical composition comprises L-carnitine or its pharmaceutically acceptable salt or ester, coenzyme Q10 or its pharmaceutically acceptable salt or ester, and a solubilizing agent, wherein the solubilizing agent comprises one or more selected from polyoxyethylene castor oil, polyoxyethylene hydrogenated castor oil, stearic acid polyoxyethylene ester and polyethylene glycol 15 hydroxy stearate . The prepared pharmaceutical composition which takes L-carnitine and coenzyme Q10 and/or their pharmaceutically acceptable salts as an active ingredient has the advantages of good stability, high security, stable preservation for long-term and safe usage; and the pharmaceutical composition can fully perform the synergy of two ingredients, has the merits of convenient usage, economical and practical effects, and possesses a good prospect.
Description
Technical field
The invention belongs to the pharmaceutical technology field, relate to a kind of levocarnitine and ubiquinone of comprising
10Pharmaceutical composition and preparation method thereof.Particularly, the present invention relates to a kind of with levocarnitine and ubiquinone
10Be compound preparation of active ingredient and preparation method thereof.
Background technology
Levocarnitine is claimed L-carnitine again, is a kind of amino acid derivativges, almost is present in all human body cells.Levocarnitine is a natural materials in the body that needs in the mammal energy metabolism, and its major function is to promote lipid metabolism.Levocarnitine strides across mitochondrial inner membrane transhipment LCFA in mitochondrion, in mitochondrion, levocarnitine generation beta oxidation produces ATP (ATP) so that the organism energy to be provided.In addition, other functions of levocarnitine have: the Oxidation of medium LCFA; The Oxidation of fatty acid peroxidase; To the cushioning effect of bonded coenzyme A and free the two ratio of coenzyme A, produce power from letones, acetone acid, aminoacid (comprising branched-chain amino acid) is removed the toxicity of too high coenzyme A, regulates ammonia concentration in the blood.
Ubiquinone
10, be called hydroquinone again, be the fat-soluble quinones that extensively exists in the organism, be a kind of vitamin or vitamin substances.Ubiquinone
10It is the coenzyme of other part enzymes of at least 3 cyclophorases and cell.The cyclophorase of oxidative phosphorylation approach is to produce high-octane phosphate, and (ATP) is requisite for adenosine triphosphate.Ubiquinone
10In the human body respiration chain, play an important role in proton displacement and the electron transport; Can be used as cellular metabolism and Cellular respiration activator; Still important antioxidants and nonspecific immunity strengthening agent have the accelerating oxidation phosphorylation reaction, protection biofilm structure integrity.
Levocarnitine and ubiquinone
10Share and have synergism, levocarnitine is that fatty acid shifts the requisite material that gets into mitochondrial matrix from Cytoplasm, and ubiquinone
10As electron carrier, these two kinds of nutrient substance generation synergism are to produce the required energy of daily routines.In addition, ubiquinone
10Also use as a kind of antioxidant with levocarnitine, protection cardiovascular function, help fat, carbohydrate and protein metabolism are kept body health so that energy to be provided.
Levocarnitine in the market and ubiquinone
10All there is single preparations of ephedrine to sell, but can generation solution muddiness phenomenon after these two kinds of preparations are directly mixed, can't use.A kind of levocarnitine and ubiquinone are disclosed among the patent CN1475211
10Compound preparation and preparation method thereof, this method for preparing adopt Tween 80 and polyoxyethylene stearate (40) ester by 1: 1 mixed next composite levocarnitine and ubiquinone of containing of solubilizing agent that gets of weight ratio
10Homogeneous phase solution, but this stability of formulation is not good enough, and toxic and side effects is big, can't realize industrialization, can not be used for the human injection safely.
Therefore, this area exists containing levocarnitine and ubiquinone at present
10Compound preparation carry out improved demand.
Summary of the invention
To above-mentioned technological deficiency, an object of the present invention is to provide a kind of pharmaceutical composition, it contains levocarnitine and ubiquinone
10Two kinds of active components, and this pharmaceutical composition can stable existence, toxic and side effects reduces.
Another object of the present invention provides this preparation of drug combination method.
Technical scheme of the present invention is following:
On the one hand, the present invention provides a kind of pharmaceutical composition, and said pharmaceutical composition comprises levocarnitine or its pharmaceutically acceptable salt or ester, ubiquinone
10Or its pharmaceutically acceptable salt or ester, and solubilizing agent, wherein said solubilizing agent is selected from one or more in polyoxyethylene castor oil, polyoxyethylene hydrogenated Oleum Ricini, polyoxyethylene stearic acid ester and the Polyethylene Glycol 15-hydroxy stearic acid ester.
Wherein, said solubilizing agent is preferably polyoxyethylene stearic acid ester and/or Polyethylene Glycol 15-hydroxy stearic acid ester.
And meter by weight, said pharmaceutical composition comprise levocarnitine or its pharmaceutically acceptable salt or 20～2000 parts of esters, ubiquinone
10Or 20～800 parts of its pharmaceutically acceptable salt or 1 part of ester and solubilizing agents;
Preferably, meter by weight, said pharmaceutical composition comprise levocarnitine or its pharmaceutically acceptable salt or 40～2000 parts of esters, ubiquinone
10Or 20～800 parts of its pharmaceutically acceptable salt or 1 part of ester and solubilizing agents;
Further preferably, meter by weight, said pharmaceutical composition comprise levocarnitine or its pharmaceutically acceptable salt or 40～1500 parts of esters, ubiquinone
10Or 20～500 parts of its pharmaceutically acceptable salt or 1 part of ester and solubilizing agents.
Pharmaceutical composition provided by the invention is with levocarnitine and ubiquinone
10Be active ingredient, wherein levocarnitine and ubiquinone
10Except that prototype, can also be its pharmaceutically acceptable salt or ester, or the derivant of said salt or ester.Particularly, said levocarnitine or ubiquinone
10Pharmaceutically acceptable salt be alkali metal salt, alkali salt, perhaps be acid salt, basic salt, inner salt.
Preferably, said pharmaceutical composition also comprises cosolvent, and said cosolvent is selected from one or more in propylene glycol, glycerin, ethanol, Polyethylene Glycol and the trometamol, thereby this pharmaceutical composition is further played Stabilization.
Pharmaceutical composition provided by the invention can be oral liquid, injection or injectable powder.Particularly, its dosage form can comprise oral liquid, injectable powder, bulk capacity injection (50ml and more than), small-volume injection (below the 50ml).The per unit preparation contains levocarnitine 0.1g～8g, ubiquinone
100.5mg～200mg, solubilizing agent 1mg～10g.
Preferably, the per unit preparation contains levocarnitine 0.1g～6g, ubiquinone
100.5mg～200mg, solubilizing agent 5mg～5g.
Wherein, when solubilizing agent is polyoxyethylene castor oil, polyoxyethylene hydrogenated Oleum Ricini or polyoxyethylene stearic acid ester, ubiquinone
10Be preferably 1: 3 with the weight ratio of solubilizing agent～200; When solubilizing agent is Polyethylene Glycol 15 hydroxy stearic acid esters, ubiquinone
10Be preferably 1: 10 with the weight ratio of solubilizing agent～400.
In addition, pharmaceutical composition of the present invention also comprises other acceptable accessories, for example stabilizing agent, correctives, etc. ooze etc. and to open in regulator, pH regulator agent and the antioxidant one or more.
Wherein stabilizing agent can be selected from one or more in phospholipid, poloxamer, gelatin, chitosan, aminoacid, sucrose ester and the Polysorbate; Correctives is selected from one or more in sweeting agent, aromatic and the mucilage; Preferably, said correctives is selected from one or more in sucrose, stevioside, aspartame, saccharin sodium, essence, sodium carboxymethyl cellulose, methylcellulose, starch, sodium alginate, arabic gum, tragakanta, agar, gelatin, citric acid, the tartaric acid; Open regulator and be selected from sodium chloride, potassium chloride, glucose, sorbitol, xylitol, mannitol and the glycerol one or more Deng oozing etc.; The pH regulator agent is selected from one or more in hydrochloric acid, acetic acid or its salt, citric acid or its salt, lactic acid, tartaric acid or its salt, phosphoric acid or its salt, carbonic acid or its salt, maleic acid or its salt, sulphuric acid, malic acid, sodium hydroxide and the potassium hydroxide; Antioxidant is selected from one or more in sulphite, vitamin C derivatives, thio-compounds, amino acids, organic acid, phenols, amine, vitamin E, ethylenediaminetetraacetic acid or its salt and the sorbitol
On the other hand, the present invention also provides the method for preparing aforementioned pharmaceutical compositions, said method comprising the steps of:
1) solubilizing agent is heated to 30～80 ℃, with ubiquinone
10And/or its pharmaceutically acceptable salt or ester are dissolved in the solubilizing agent; And adding ubiquinone
10And/or randomly add cosolvent before or after its pharmaceutically acceptable salt or the ester;
2) levocarnitine and/or its pharmaceutically acceptable salt or ester and optional other acceptable accessories is water-soluble;
3) merge respectively through step 1) and step 2) solution that obtains, the pH of regulator solution is 3 to 9, preferred 4 to 8, the adding active carbon takes off charcoal after the stirring.
Said method also comprises processes the step of injectable powder with taking off solution lyophilizing behind the charcoal.
Below be detailed description of the present invention:
Ubiquinone
10Water-soluble hardly, therefore, in the preparation process, need to add solubilizing agent to ubiquinone
10Carry out solubilising, mostly solubilizing agent commonly used is nonionic surfactant, and it is directly related with the concentration of salt in the solution that non-ionic surface active forms micellar stability, and the salt amount increases, and solubilizing effect and stability of solution all descend.Levocarnitine in this compositions can reduce solubilizing agent to ubiquinone as a kind of salt
10Solubilization, make ubiquinone
10The solubilising difficulty that becomes more, make it in storage process, be easier to separate out, and prior art all can not be realized.The specific non-ionic surface active agent of acceptable for pharmaceutical that the present invention selects is as solubilizing agent, in amount ranges of the present invention, to ubiquinone
10Solubilizing effect good, can make stable compositions, can realize industrialization, toxic and side effects is little, can be used safely in the human injection.
The inventor finds that in the selection course of solubilizing agent using solubilizing agent separately all can make ubiquinone
10Solubilising; But behind the adding levocarnitine then medicine be easy to separate out, the prescription that for example contains poly yamanashi esters is easy to separate out, its reason is that levocarnitine adds the character that affiliation changes non-ionic surface active agent as salt; Make it have more lipophile, thereby the solubilizing effect of medicine in water reduced.In order to improve solubilizing effect; The present invention is directed to existing solubilizing agent and carried out a large amount of screenings and experiment; The result finds under the situation that adds levocarnitine, adopts polyoxyethylene stearic acid ester, polyoxyethylene castor oil, polyoxyethylene hydrogenated Oleum Ricini and/or Polyethylene Glycol 15 hydroxy stearic acid esters can make ubiquinone
10Solubilising effectively.In addition, sensitization possibly occur during owing to polyoxyethylene castor oil, polyoxyethylene hydrogenated Oleum Ricini injection, so this adjuvant only is used for the application of oral liquid.In the drug administration by injection approach, the preferred solubilizing agent of the present invention is polyoxyethylene stearic acid ester class, Polyethylene Glycol 15 hydroxy stearic acid esters, and these two types of solubilizing agents are to ubiquinone
10Solubilizing effect better, and add behind the levocarnitine lessly to the stability of formulation influence, the phenomenon that medicine is separated out can not take place in storage period, in addition, also can add phospholipid, poloxamer etc. and share to increase the stability of solution.The solubilizing agent that the present invention is used is the pharmaceutic adjuvant that domestic and international approved is used to inject, and has good safety.
Find also that in development process of the present invention adding in a certain amount of cosolvent such as propylene glycol, glycerin, ethanol, Polyethylene Glycol and the trometamol one or more can have Stabilization to prescription.
On the other hand, can also comprise correctives as the oral liquid of one of way of realization of compound preparation of the present invention, it can be selected from sweeting agent, aromatic and the mucilage one or more.
On the other hand, also comprise in mannitol, dextran, lactose, glucose, sorbitol, sucrose, gelatin, trehalose, sodium chloride, polyvinylpyrrolidone, citric acid or its salt citrate, pantothenic acid or its salt, aspartic acid, vitamin C, glycine or its salt, cholate, phosphoric acid or its salt, aminoacid or its salt, the cyclodextrin or derivatives thereof one or more as the lyophilized injectable powder of one of way of realization of compound preparation of the present invention.
On the other hand; Compound preparation of the present invention; Can also comprise that some conventional injecting drug uses use acceptable auxiliary, comprise etc. oozing etc. and open regulator that it can be selected from sodium chloride, potassium chloride, glucose, sorbitol, xylitol, mannitol and the glycerol one or more.The pH regulator agent, it can be selected from hydrochloric acid, acetic acid or its salt, citric acid or its salt, lactic acid, tartaric acid or its salt, phosphoric acid or its salt, carbonic acid or its salt, maleic acid or its salt, sulphuric acid, malic acid, sodium hydroxide, the potassium hydroxide one or more.Antioxidant, intercalating agent, it can be selected from sulphite, vitamin C derivatives, thio-compounds, amino acids, organic acid, phenols, amine, vitamin E, ethylenediaminetetraacetic acid or its salt, the sorbitol one or more.
CN1475211 provides with levocarnitine and ubiquinone
10Be the compound preparation of active ingredient, it contains tween and polyoxyl stearate as solubilizing agent.Compare with this prior art, the present invention prepared with levocarnitine and ubiquinone
10Or its pharmaceutically acceptable salt or ester be the pharmaceutical composition of active ingredient, has good stability, and safe advantage experiment showed, under the prerequisite of not using the Tweens solubilizing agent with toxic and side effects, and it can steady in a long-termly be preserved and safe handling; And this pharmaceutical composition can be given full play to the synergism that two medicines share, and is easy to use, economical and practical, has a good application prospect.
The specific embodiment
Below in conjunction with the specific embodiment the present invention is further described in detail, the embodiment that provides has been merely and has illustrated the present invention, rather than in order to limit scope of the present invention.
Experimental technique among the following embodiment like no specified otherwise, is conventional method.Used medicinal raw material, reagent material etc. like no specified otherwise, are commercially available purchase product among the following embodiment.
Embodiment 1The selection of solubilizing agent in compound recipe levocarnitine and the coenzyme Q10
Prepare preparation according to ingredient in the unit dosage forms shown in the table 1.
The design of table 1 prescription
Sample 1 to 5 preparation technology: solubilizing agent is heated to 50～60 ℃, with ubiquinone
10Be dissolved in the solubilizing agent,, add active carbon, take off charcoal after the stirring, add the injection water and be settled to 500ml, filter with hydrochloric acid adjust pH to 5.0, fill, sterilization is observed the medicinal liquid character in 40 ℃ of held.
Sample 6 to 16 preparation technologies: solubilizing agent is heated to 50～60 ℃, with ubiquinone
10Be dissolved in the solubilizing agent, add after levocarnitine is dissolved in water,, add active carbon, take off charcoal after the stirring, add the injection water and be settled to 500ml, filter with hydrochloric acid adjust pH to 5.0, fill, sterilization is observed the medicinal liquid character in 40 ℃ of held.
The result of each sample sees table 2.
Table 2 stability result
| 0 day | 5 days | 10 days | 1 month | 3 months | |
| 1 | Yellow settled solution | Yellow settled solution | Yellow settled solution | Yellow settled solution | Yellow settled solution |
| 2 | Yellow settled solution | Yellow settled solution | Yellow settled solution | Yellow settled solution | Yellow settled solution |
| 3 | Yellow settled solution | Yellow settled solution | Yellow settled solution | Yellow settled solution | Yellow settled solution |
| 4 | Yellow settled solution | Yellow settled solution | Yellow settled solution | Yellow settled solution | Yellow settled solution |
| 5 | Yellow settled solution | Yellow settled solution | Yellow settled solution | Yellow settled solution | Yellow settled solution |
| 6 | Yellow settled solution | Separate out yellow crystal | Separate out yellow crystal | Do not observe | Do not observe |
| 7 | Yellow settled solution | Yellow settled solution | Separate out yellow crystal | Do not observe | Do not observe |
| 8 | Yellow settled solution | Yellow settled solution | Separate out yellow crystal | Do not observe | Do not observe |
| 9 | Yellow settled solution | Yellow settled solution | Separate out yellow crystal | Do not observe | Do not observe |
| 10 | Yellow settled solution | Yellow settled solution | Separate out yellow crystal | Do not observe | Do not observe |
| 11 | Yellow settled solution | Yellow settled solution | Yellow settled solution | Yellow settled solution | Yellow settled solution |
| 12 | Yellow settled solution | Yellow settled solution | Yellow settled solution | Yellow settled solution | Yellow settled solution |
| 13 | Yellow settled solution | Yellow settled solution | Yellow settled solution | Yellow settled solution | Yellow settled solution |
| 14 | Yellow settled solution | Yellow settled solution | Yellow settled solution | Yellow settled solution | Yellow settled solution |
| 15 | Yellow settled solution | Yellow settled solution | Yellow settled solution | Yellow settled solution | Yellow settled solution |
| 16 | Yellow settled solution | Yellow settled solution | Yellow settled solution | Yellow settled solution | Yellow settled solution |
Can know from table 2 data, in compound preparation, only contain ubiquinone
10When (sample 1 to 5), the solubilizing agent of being surveyed can both make its stable preservation, and no crystallization is separated out.But after wherein adding levocarnitine, adopt tween 80 just to separate out yellow crystal (sample 6) after 5 days as the preparation of solubilizing agent, and the preparation that contains the solubilizing agent that the present invention selects after 5 days no crystallization separate out, separate out crystallization (sample 7-10) after 10 days.
In order further to improve the stability of compound formulation, through the ratio of levocarnitine, coenzyme Q10 and solubilizing agent in the adjustment compound preparation, can realize that compound preparation keeps the regular period stable, (sample 11 to 16) separated out in no crystallization after 1 month.
Embodiment 2 levocarnitines and ubiquinone
10
Oral liquid
Prescription:
Method for preparing:
Get the polyoxyethylene castor oil EL35 of recipe quantity, be heated to 30～40 ℃, add ubiquinone
10, stir and make its dissolving;
Other gets the purified water of recipe quantity 70%, and the aspartame that adds recipe quantity stirs and makes its dissolving, and the levocarnitine that adds recipe quantity stirs and makes its dissolving;
Mix above-mentioned two kinds of medicinal liquids, add malic acid and transfer pH to 4.0, add the active carbon of cumulative volume 0.5%, stir, after 30 minutes, take off charcoal, add purified water to cumulative volume, fine straining, fill, sterilization promptly gets.
Embodiment 3 levocarnitines and ubiquinone
10
Injection
Method for preparing:
Get Polyethylene Glycol 15 hydroxy stearic acid esters of recipe quantity, be heated to 50～60 ℃, add ubiquinone
10, stir and make its dissolving;
Other gets the water for injection of recipe quantity 70%, and the levocarnitine that adds recipe quantity stirs and makes its dissolving;
Mix above-mentioned two kinds of medicinal liquids, add hydrochloric acid and transfer pH to 4.5, add the active carbon of cumulative volume 0.5%, stir, after 30 minutes, take off charcoal, add the injection water to cumulative volume, fine straining, fill is sealed, and sterilization promptly gets.
Embodiment 4 levocarnitines and ubiquinone
10
Injection
Prescription:
Method for preparing:
Get the polyoxyethylene stearic acid ester of recipe quantity, be heated to 50～60 ℃, add ubiquinone
10, stir and make its dissolving, add the propylene glycol of equal temperature;
Other gets the water for injection of recipe quantity 70%, and the levocarnitine that adds recipe quantity stirs and makes its dissolving;
Mix above-mentioned two kinds of medicinal liquids, add malic acid and transfer pH to 5.0, add the active carbon of cumulative volume 0.5%, stir, after 30 minutes, take off charcoal, add the injection water to cumulative volume, fine straining, fill is sealed, and sterilization promptly gets.
Embodiment 5 levocarnitines and ubiquinone
10
Transfusion
Prescription:
Method for preparing:
Get Polyethylene Glycol 15 hydroxy stearic acid esters of recipe quantity, be heated to 70～80 ℃, add ubiquinone
10, stir and make its dissolving, add the glycerin of equal temperature;
Other gets the water for injection of recipe quantity 70%, and the levocarnitine, the sodium chloride that add recipe quantity stir and makes its dissolving;
Mix above-mentioned two kinds of medicinal liquids, add phosphoric acid and transfer pH to 6.0, add the active carbon of cumulative volume 0.5%, stir, after 30 minutes, take off charcoal, add the injection water to cumulative volume, fine straining, fill is sealed, and sterilization promptly gets.
Embodiment 6 levocarnitines and ubiquinone
10
Freeze-dried powder
Method for preparing:
Get Polyethylene Glycol 15 hydroxy stearic acid esters of recipe quantity, be heated to 50～60 ℃, add ubiquinone
10, stir and make its dissolving;
Other gets the water for injection of recipe quantity 70%, and the levocarnitine that adds recipe quantity stirs and makes its dissolving, and adding recipe quantity poloxamer, mannitol make its dissolving;
Mix above-mentioned two kinds of medicinal liquids, add hydrochloric acid and transfer pH to 8.0, add the active carbon of cumulative volume 0.5%, stir, after 30 minutes, take off charcoal, add the injection water to cumulative volume, fine straining, fill, lyophilizing promptly gets.
Wherein freeze-dry process is:
Shelf temperature is established below-40 ℃ and is carried out pre-freeze, and products temperature kept 180 minutes at-40 ℃, and case vacuum value reached below the 15pa before evacuation made; Shelf is not less than-10 ℃ and carries out primary drying; Products temperature reaches～5 ℃ after, shelf is established 25 ℃ and is carried out redrying, after products temperature reaches 30 ℃; Tamponade is advanced pure air and is pressed the back outlet again.The lyophilizing overall process is moved about 20 hours.
Embodiment 7 study on the stability
Experimentize by two appendix XIXC of Chinese Pharmacopoeia version in 2010 stability test guideline; Key index to the compound preparation of the levocarnitine of embodiment of the invention preparation and coenzyme Q10: character, pH value, clarity of solution and color, visible foreign matters, related substance, content and aseptic the detection; And carry out study on the stability simultaneously by patent CN1475211 embodiment 1 (Comparative Examples) preparation sample, testing result is seen table 3 and 4:
Table 3 sample quickens to investigate the result
Table 4 sample long-term investigation result
Embodiment 8 levocarnitines and ubiquinone
10
Injection zest, anaphylaxis, hemolytic experiment
Embodiment 7 prepared samples are experimentized by " chemicals zest, anaphylaxis and hemolytic investigative technique guideline ", and the result shows prepared injection nonirritant, anaphylaxis and hemolytic, explains that the safety of preparation is very high.
Claims (9)
1. a pharmaceutical composition is characterized in that, said pharmaceutical composition comprises levocarnitine or its pharmaceutically acceptable salt or ester, ubiquinone
10Or its pharmaceutically acceptable salt or ester and solubilizing agent; Wherein said solubilizing agent is selected from one or more in polyoxyethylene castor oil, polyoxyethylene hydrogenated Oleum Ricini, polyoxyethylene stearic acid ester and Polyethylene Glycol 15 hydroxy stearic acid esters, is preferably polyoxyethylene stearic acid ester and/or Polyethylene Glycol 15 hydroxy stearic acid esters.
2. pharmaceutical composition according to claim 1 is characterized in that, meter by weight, said pharmaceutical composition comprise levocarnitine or its pharmaceutically acceptable salt or 20～2000 parts of esters, ubiquinone
10Or 20～800 parts of its pharmaceutically acceptable salt or 1 part of ester and solubilizing agents;
Preferably, meter by weight, said pharmaceutical composition comprise levocarnitine or its pharmaceutically acceptable salt or 40～2000 parts of esters, ubiquinone
10Or 20～800 parts of its pharmaceutically acceptable salt or 1 part of ester and solubilizing agents;
Further preferably, meter by weight, said pharmaceutical composition comprise levocarnitine or its pharmaceutically acceptable salt or 40～1500 parts of esters, ubiquinone
10Or 20～500 parts of its pharmaceutically acceptable salt or 1 part of ester and solubilizing agents.
3. pharmaceutical composition according to claim 1 and 2 is characterized in that, levocarnitine or ubiquinone
10Pharmaceutically acceptable salt be alkali metal salt, alkali salt, perhaps be acid salt, basic salt, inner salt.
4. according to each described pharmaceutical composition in the claim 1 to 3, it is characterized in that said pharmaceutical composition also comprises cosolvent, said cosolvent is selected from one or more in propylene glycol, glycerin, ethanol, Polyethylene Glycol and the trometamol.
5. according to each described pharmaceutical composition in the claim 1 to 4, it is characterized in that said pharmaceutical composition is oral liquid, injection or injectable powder.
6. according to each described pharmaceutical composition in the claim 1 to 5, it is characterized in that said pharmaceutical composition also comprises other acceptable accessories;
Preferably, said other acceptable accessories be selected from stabilizing agent, correctives, etc. ooze etc. and to open in regulator, pH regulator agent and the antioxidant one or more.
7. pharmaceutical composition according to claim 6 is characterized in that said stabilizing agent is selected from one or more in phospholipid, poloxamer, gelatin, chitosan, aminoacid, sucrose ester and the Polysorbate;
Said correctives is selected from one or more in sweeting agent, aromatic and the mucilage; Preferably, said correctives is selected from one or more in sucrose, stevioside, aspartame, saccharin sodium, essence, sodium carboxymethyl cellulose, methylcellulose, starch, sodium alginate, arabic gum, tragakanta, agar, gelatin, citric acid, the tartaric acid;
Said grade is oozed etc. and to be opened regulator and be selected from sodium chloride, potassium chloride, glucose, sorbitol, xylitol, mannitol and the glycerol one or more;
Said pH regulator agent is selected from one or more in hydrochloric acid, acetic acid or its salt, citric acid or its salt, lactic acid, tartaric acid or its salt, phosphoric acid or its salt, carbonic acid or its salt, maleic acid or its salt, sulphuric acid, malic acid, sodium hydroxide and the potassium hydroxide;
Said antioxidant is selected from one or more in sulphite, vitamin C derivatives, thio-compounds, amino acids, organic acid, phenols, amine, vitamin E, ethylenediaminetetraacetic acid or its salt and the sorbitol.
8. preparation is characterized in that according to the method for each described pharmaceutical composition in the claim 1 to 7, said method comprising the steps of:
1) solubilizing agent is heated to 30～80 ℃, with ubiquinone
10And/or its pharmaceutically acceptable salt or ester are dissolved in the solubilizing agent; And adding ubiquinone
10And/or randomly add cosolvent before or after its pharmaceutically acceptable salt or the ester;
2) levocarnitine and/or its pharmaceutically acceptable salt or ester and optional other acceptable accessories is water-soluble;
3) merge respectively through step 1) and step 2) solution that obtains, the pH of regulator solution is 3 to 9, preferred 4 to 8, the adding active carbon takes off charcoal after the stirring.
9. method according to claim 8 is characterized in that, said method also comprises processes the step of injectable powder with taking off solution lyophilizing behind the charcoal.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2012100257327A CN102552923A (en) | 2012-01-31 | 2012-01-31 | Pharmaceutical composition containing L-carnitine and coenzyme Q10 as well as its preparation method |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2012100257327A CN102552923A (en) | 2012-01-31 | 2012-01-31 | Pharmaceutical composition containing L-carnitine and coenzyme Q10 as well as its preparation method |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN102552923A true CN102552923A (en) | 2012-07-11 |
Family
ID=46400372
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN2012100257327A Pending CN102552923A (en) | 2012-01-31 | 2012-01-31 | Pharmaceutical composition containing L-carnitine and coenzyme Q10 as well as its preparation method |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN102552923A (en) |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103976960A (en) * | 2014-05-18 | 2014-08-13 | 严白双 | Levocarnitine freeze-dried composition for injection and preparation method thereof |
| CN105853347A (en) * | 2016-04-01 | 2016-08-17 | 海南合瑞制药股份有限公司 | Levocarnitine composition and preparation method thereof |
| CN113292622A (en) * | 2021-05-31 | 2021-08-24 | 吉林浩泰健康产业发展有限公司 | Method for extracting beta-sitosterol from pimpinella brachycarpa and application of beta-sitosterol |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1475211A (en) * | 2003-06-24 | 2004-02-18 | 广州贝氏药业有限公司 | Compound preparation of levocarnitine and coenzyme Q10 |
| US20050037068A1 (en) * | 2001-11-09 | 2005-02-17 | Massironi Maria Gabriella | Solid, stabilized, prompt-and/or modified-release therapeutical systems for the oral administration of liquid active principles, excipients or foodstuffs |
| CN101011373A (en) * | 2007-02-15 | 2007-08-08 | 宛六一 | Pharmaceutical composition containing L-carnitine and preparation method thereof |
-
2012
- 2012-01-31 CN CN2012100257327A patent/CN102552923A/en active Pending
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20050037068A1 (en) * | 2001-11-09 | 2005-02-17 | Massironi Maria Gabriella | Solid, stabilized, prompt-and/or modified-release therapeutical systems for the oral administration of liquid active principles, excipients or foodstuffs |
| CN1475211A (en) * | 2003-06-24 | 2004-02-18 | 广州贝氏药业有限公司 | Compound preparation of levocarnitine and coenzyme Q10 |
| CN101011373A (en) * | 2007-02-15 | 2007-08-08 | 宛六一 | Pharmaceutical composition containing L-carnitine and preparation method thereof |
Non-Patent Citations (3)
| Title |
|---|
| 刘红霞: "《药物辅料速查手册》", 31 July 2007 * |
| 易红等: "几种注射用表面活性剂的质量标准及安全性概述", 《中国实验方剂学杂志》 * |
| 李玉林: "注射用辅酶Q_（10）的制剂研究", 《中国优秀硕士学位论文全文数据库 医药卫生科技辑》 * |
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103976960A (en) * | 2014-05-18 | 2014-08-13 | 严白双 | Levocarnitine freeze-dried composition for injection and preparation method thereof |
| CN103976960B (en) * | 2014-05-18 | 2016-01-06 | 严白双 | A kind of levo-carnitine for injection freeze-dried composition and preparation method thereof |
| CN105853347A (en) * | 2016-04-01 | 2016-08-17 | 海南合瑞制药股份有限公司 | Levocarnitine composition and preparation method thereof |
| CN113292622A (en) * | 2021-05-31 | 2021-08-24 | 吉林浩泰健康产业发展有限公司 | Method for extracting beta-sitosterol from pimpinella brachycarpa and application of beta-sitosterol |
| CN113292622B (en) * | 2021-05-31 | 2022-03-29 | 吉林浩泰健康产业发展股份有限公司 | Method for extracting beta-sitosterol from pimpinella brachycarpa and application of beta-sitosterol |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| EP2184100A1 (en) | A composite emulsifier, an emulsion prepared from it and the preparation method thereof | |
| CA2559938A1 (en) | Tissue detoxification and health supplements and methods of making and using them | |
| CN102579341A (en) | Docetaxel solid lipid nanoparticle and preparation method thereof | |
| CN102068453A (en) | Stable complex vitamin composite and preparation method thereof | |
| CN101716149B (en) | Precursor medicinal preparation | |
| CN114869848B (en) | Butylphthalide micelle composition and preparation process thereof | |
| CN102552923A (en) | Pharmaceutical composition containing L-carnitine and coenzyme Q10 as well as its preparation method | |
| CN102429864B (en) | Medicinal compound of fat-soluble vitamin injection (II) and water-soluble vitamin for injection and preparation method thereof | |
| CN102512437A (en) | Medicinal composition of liposoluble vitamin injection (I) and water-soluble vitamin for injection and preparation method thereof | |
| CN102657663B (en) | Fat-soluble composite vitamin I composition freeze-dried powder injection and preparation method thereof | |
| CN101890022B (en) | Cefoperazone sodium and tazobactam sodium medicament composition liposome injection | |
| CN103169756B (en) | Pharmaceutical composition of water-soluble vitamins for injection, fat-soluble vitamin injection and fat emulsion injection | |
| CN102357081A (en) | Composite fat-soluble vitamin freeze-dried powder injection and preparation method thereof | |
| CN111465389B (en) | Pharmaceutical composition of docetaxel conjugate and preparation method thereof | |
| CN104606209A (en) | Compound vitamin medicine composition for injection and preparation method of compound vitamin medicine composition | |
| CN103768088B (en) | Pharmaceutical composition containing water-soluble vitamins for injection, fat-soluble vitamins for injection and medium/long-chain fat emulsion injection | |
| CN101129374B (en) | Vinflunine pharmaceutical composition and method of producing the same and application of the same | |
| CN103169755B (en) | Pharmaceutical composition of water-soluble vitamins for injection, fat-soluble vitamins for injection and fat emulsion injection | |
| CN102488664B (en) | Pharmaceutical composition containing 12 vitamins | |
| CN102188370B (en) | Resveratrol injection solution and intravenous injection | |
| CN103768132B (en) | Pharmaceutical composition containing water-soluble vitamins for injection, fat-soluble vitamin injection and medium/long-chain fat emulsion injection | |
| US20050209170A1 (en) | Breast health preparations | |
| CN103126992B (en) | Fat-soluble vitamin composite powder and preparation method thereof | |
| CN102526089A (en) | Pharmaceutical composition containing 13 kinds of vitamins | |
| CN1895262A (en) | Emulsion for injecting epirubicin and its production |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C12 | Rejection of a patent application after its publication | ||
| RJ01 | Rejection of invention patent application after publication |
Application publication date: 20120711 |