CN1679542A - Frozen powder injection of silybin and its preparing method - Google Patents
Frozen powder injection of silybin and its preparing method Download PDFInfo
- Publication number
- CN1679542A CN1679542A CN 200410023873 CN200410023873A CN1679542A CN 1679542 A CN1679542 A CN 1679542A CN 200410023873 CN200410023873 CN 200410023873 CN 200410023873 A CN200410023873 A CN 200410023873A CN 1679542 A CN1679542 A CN 1679542A
- Authority
- CN
- China
- Prior art keywords
- silibinin
- phase
- salt
- dried powder
- freeze
- 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
A freeze-dried powder injection of silibinin salt features that it contains silibinin salt which may be the inorganic or organic alkaline salt of silibinin or its salt of amino acid, the pH regulator and/or solubilizer.
Description
Technical field
The present invention relates to a kind of is effective ingredient with silibinin salt, and clinical freeze-dried powder that is used for the treatment of acute and chronic hepatitis and preparation method thereof relates to freeze-dried powder of the organic alkali salt of silibinin, inorganic base salts or alkaline amino acid salt and preparation method thereof particularly.
Background technology
Herba Silybi mariani is a feverfew, originates in southern Europe and north African, the hepatic disease that is used for the treatment of among the people.Nineteen sixty-eight Wagner etc. therefrom extracts a kind of flavone compound, called after silymarin (Silymarin), the main component that has now proved silymarin is silibinin (Silybin), its chemical name is: 2-(2,3-Dihydro-2-(4-hydroxy-3-methoxyphenyl)-3-(hydroxymethyl)-1,4-benzodioxin-6-yl)-2,3-dihydro-3,5,7-trihydroxy-4H-1-benzopyran-4-one, the clinical acute hepatitis that is used for, chronic hepatitis, first cirrhosis, fatty liver, toxic hepatitis (as taking prejudicial medicine of hepatocyte or frequent heavy drinking) protects the liver.Modern pharmacology studies show that silibinin has clear and definite protective effect to multiple hepatic injury.The silibinin salt of listing is for being silybin meglumine at present, and English name: Silybin Meglumine, its active component still are silibinin, but the dissolubility in water is far longer than silibinin.Existing kind is silybin meglumine tablets (national drug standards [WS-1001-(HD-0926)-2002]) on the silybin meglumine market, in addition, publication number be CN 1418637 A patent report a kind of " treatment hepatitis silybin meglumine dispersible tablet and preparation method thereof ".
Silibinin is water insoluble, and oral administration biaavailability is lower, is generally 20%～30%, and individual variation is bigger.Silybin meglumine is a weak acid and weak base salt, and water solublity is better, but still can separate out silibinin under acid condition.Separate out under one's belt after the silybin meglumine oral application, still can influence the absorption of silibinin.Can play therapeutical effect though take in a large number, can cause certain untoward reaction to take place,, also cause the waste of drug resource as the upper abdomen discomfort etc.In addition to some emergency and severe disease patients in when treatment, the speed that oral administration absorbs is slower, often delay treatment opportunity, causes unnecessary loss to the patient.The silybin meglumine dispersible tablet of silybin meglumine tablets in the national drug standards and patent report is oral administration, all has above-mentioned shortcoming.
Silybin meglumine is when the preparation lyophilized preparation, at first need to be mixed with aqueous solution, and the aqueous solution of silybin meglumine at ambient temperature, promptly becomes turbid in 30 minutes, can't satisfy production to the needs of time, dried frozen aquatic products in this case can't use clinically.
This patent has proposed the method for three head it offs, and the one, add solubilizing agent, the 2nd, regulate pH value, the 3rd, not only add solubilizing agent but also regulate pH; Thereby guarantee solution clear in 4 hours of preparation, satisfied the requirement of producing, simultaneously, meet clinical instructions for use behind the lyophilized preparation compatibility normal saline the time; In addition, the process using that this patent relates to lyophilization, production process is finished under the temperature the end of than, and the vacuum tamponade, makes stability of drug improve greatly.This patent has not only creatively solved silibinin aqueous solution short time internal haze, the problem that can't produce lyophilized preparation, and the preparation lyophilized preparation possess remarkable advantages, accord with the demands of the market.
The invention provides and be suitable for suitability for industrialized production, steady quality, be convenient to that transportation stores and can quick-dissolving silybin meglumine lyophilized preparation.
Summary of the invention
The invention provides silibinin salt freeze-dried powder.Silibinin salt can be silibinin inorganic base salts, the organic alkali salt of silibinin or silibinin amino acid salts.The silibinin inorganic base salts is selected from: silibinin sodium salt, silibinin potassium salt, silibinin ammonium salt; The organic alkali salt of silibinin is selected from: silybin-N-methylglucamine, silibinin amine salt; The silibinin amino acid salts is selected from: silibinin arginine salt, silibinin lysinate.Silibinin salt is preferably silybin meglumine.
The present invention also provides the preparation method of preparation Herba Silybi mariani freeze-dried powder.
Herba Silybi mariani freeze-dried powder provided by the invention contains PH regulator, solubilizing agent or its group.The PH regulator is selected from one or more in sodium hydroxide, potassium hydroxide, meglumine, sodium carbonate, the potassium carbonate; Solubilizing agent is selected from one or more in 2-HP-, beta-schardinger dextrin-, sulfobutyl ether-beta-schardinger dextrin-, alpha-cyclodextrin, gamma-cyclodextrin, polyvinylpyrrolidone, the Polyethylene Glycol.When freeze-dried powder provided by the invention added water to the lyophilized powder equal-volume, its pH value of aqueous solution was 7-12, is preferably 9-11.Freeze-dried powder provided by the invention can also contain one or more in excipient, antioxidant, the complexing of metal ion agent.Excipient is selected from one or more in mannitol, sucrose, lactose, arginine, lysine, glycine, sorbitol, the low molecular dextran; Antioxidant is selected from one or more in sodium thiosulfate, sodium sulfite, thiourea, the vitamin C; The complexing of metal ion agent is selected from one or more among EDTA-4Na, EDTA-2Na, the EDTA.
The preparation method of freeze-dried powder provided by the invention is: preparation contains the aqueous solution of solubilizing agent in proportion; Silibinin salt places the aqueous solution of above-mentioned solubilizing agent in proportion, stirs to make dissolving; Regulating pH value with the pH regulator agent is 7-12; By requirement sterilization, the depyrogenation of injection, filtering with microporous membrane, packing; Lyophilization.Lyophilization divided for three phases; The first phase, the quick freezing phase; Speed cooling with per minute 1-10 ℃ drops to-30 to-50 ℃ until solution temperature, keeps 2-5 hour; The second phase, the distillation phase (removing Free water); Evacuation makes vacuum between 50-500 μ bas, and temperature was kept 5-20 hour between-30 to-10 ℃; The third phase, the redrying phase (removing bound water).Vacuum remains on 50-500 μ bas, and temperature remains on 0-50 ℃, and this process was kept 2 to 10 hours; The vacuum tamponade, promptly.
The preparation method of freeze-dried powder provided by the invention is: get silibinin salt in proportion and place aqueous solution, regulating pH value with the pH regulator agent is 10-12; By requirement sterilization, the depyrogenation of injection, filtering with microporous membrane, packing; Lyophilization.Lyophilization divided for three phases.The first phase, the quick freezing phase.Speed cooling with per minute 1-10 ℃ drops to-30 to-50 ℃ 2 until solution temperature, keeps 2-5 hour; The second phase, the distillation phase (removing Free water).Evacuation makes vacuum between 50-500 μ bas, and temperature was kept 5-20 hour between-30 to-10 ℃; The third phase, the redrying phase (removing bound water).Vacuum remains on 50-500 μ bas, and temperature remains on 0-50 ℃, and this process was kept 2 to 10 hours.
Silybin meglumine lyophilized preparation involved in the present invention all complies with relevant regulations in the check of items such as content, pyrogen, antibacterial, pH value, clarity.
The specific embodiment
Embodiment 1:
Dosing: take by weighing silybin meglumine 500.00g, place container, add mannitol 100g, sodium sulfite 10g, EDTA-2Na0.5g adds water and makes dissolving in right amount, transfers pH to 10.5 with sodium hydroxide solution, adds water to 10000ml, stirs; Filtration, packing: adopt 0.22 μ filtering with microporous membrane, filtrate is by every 2.0ml packing; Lyophilization: the speed cooling with 5 ℃ of per minutes, be cooled to-40 ℃ until product, kept 3 hours; The beginning evacuation, control vacuum is at 100 ± 50 μ bas, and product temperature is controlled at-20 ℃, keeps 15 hours; Then, progressively be warming up to 20 ℃, control vacuum at 200 ± 50 μ bas, reach 20 ℃ 2 after, continued to keep 3 hours, the vacuum tamponade, promptly.
Embodiment 2:
Dosing: take by weighing 2-HP-100.00g, add water and make dissolving, take by weighing silybin meglumine 100.00g, place above-mentioned solution, stir; Add lactose 400g again, sodium thiosulfate 3.0g, EDTA-2Na0.5g stirs and makes dissolving, transfers pH to 9 with sodium hydroxide solution, adds water to 10000ml, stirs; Filtration, packing: adopt 0.22 μ filtering with microporous membrane, filtrate is by every 1.0ml packing; Lyophilization: the speed cooling with 5 ℃ of per minutes, be cooled to-40 ℃ until product, kept 3 hours; The beginning evacuation, control vacuum is at 100 ± 50 μ bas, and product temperature is controlled at-20 ℃, keeps 15 hours; Then, progressively be warming up to 20 ℃, control vacuum at 200 ± 50 μ bas, reach 20 ℃ 2 after, continued to keep 3 hours, the vacuum tamponade, promptly.
Embodiment 3:
Dosing: take by weighing 2-HP-50.00g, add water and make dissolving, take by weighing silybin meglumine 100.00g, place above-mentioned solution, stir; Add mannitol 400g again, sodium thiosulfate 5.0g, EDTA-2Na0.5g stirs and makes dissolving, transfers pH to 9.5 with sodium hydroxide solution, adds water to 10000ml, stirs; Filtration, packing: adopt 0.22 μ filtering with microporous membrane, filtrate is by every 2.0ml packing; Lyophilization: the speed cooling with 5 ℃ of per minutes, be cooled to-40 ℃ until product, kept 3 hours; The beginning evacuation, control vacuum is at 100 ± 50 μ bas, and product temperature is controlled at-20 ℃, keeps 15 hours; Then, progressively be warming up to 20 ℃, control vacuum at 200 ± 50 μ bas, reach 20 ℃ after, continued to keep 3 hours, the vacuum tamponade, promptly.
Embodiment 4:
Preparation silibinin sodium salt solution: take by weighing silibinin 24g, put in the reaction vessel, add 500ml water, adopt magnetic stirrer, slowly add sodium hydrate aqueous solution (1mol/L) 50ml while stirring, continue to be stirred to silibinin and dissolve fully; Dosing: take by weighing mannitol 40g, join in the top solution, stir and make dissolving, transfer pH to 10, add water to 1000ml, stir with sodium hydroxide solution; Filtration, packing: adopt 0.22 μ filtering with microporous membrane, filtrate is by every 2.0ml packing; Lyophilization: the speed cooling with 5 ℃ of per minutes, be cooled to-40 ℃ until product, kept 3 hours; The beginning evacuation, control vacuum is at 100 ± 50 μ bas, and product temperature is controlled at-20 ℃, keeps 15 hours; Then, progressively be warming up to 20 ℃, control vacuum at 200 ± 50 μ bas, reach 20 ℃ after, continued to keep 3 hours, the vacuum tamponade, promptly.
Embodiment 5:
Preparation silibinin arginine salt: take by weighing silibinin 4.8g, put in the reaction vessel, add 95% ethanol 100ml, adopt magnetic stirrer, slowly add simultaneously arginine aqueous solution (0.1mol/L) 120ml, suitably heating continues to be stirred to silibinin and dissolves fully, drying under reduced pressure gets the silibinin arginine.Dosing: take by weighing 2-HP-10g, add water 150ml and make dissolving.Get above-mentioned silibinin arginine and be added in this solution, add mannitol 10g again, sodium thiosulfate 0.1g transfers pH to 9.5 with sodium hydroxide solution, stirs and makes dissolving fully, adds water to 200ml, stirs; Filtration, packing: adopt 0.22 μ filtering with microporous membrane, filtrate is by every 1.0ml packing; Lyophilization: the speed cooling with 5 ℃ of per minutes, be cooled to-40 ℃ until product, kept 3 hours; The beginning evacuation, control vacuum is at 100 ± 50 μ bas, and product temperature is controlled at-20 ℃, keeps 15 hours; Then, progressively be warming up to 20 ℃, control vacuum at 200 ± 50 μ bas, reach 20 ℃ after, continued to keep 3 hours, the vacuum tamponade, promptly.
Test example 1: injection silybin meglumine lyophilized preparation and meglumine tablets effect are relatively
Experiment material:
Silybin meglumine freeze-dried powder (Silybin powder pin) is pressed embodiment 1 preparation, and 50mg/ props up, lot number: 20030911.Silybin meglumine tablets (Silybin sheet), Jiangsu Zhongxing Pharmaceutical Co., Ltd. produces, 50mg/ sheet, lot number: 20030803.Bifendate drop pill, Dezhou, Shandong Province pharmaceutical factory produces, 1.5mg/ ball, lot number: 030205.Glutamic oxaloacetic transaminase, GOT (GOT) is measured test kit, lot number: 20030501, and glutamate pyruvate transaminase (GPT) is measured test kit, lot number: 20030602, reitman-frankel method is measured, and Shanghai Rongsheng Bioisystech Co., Ltd produces.
Animal:
Kunming mouse, male, body weight 18 ~ 22g, Shandong Province's natural drug Engineering Technical Research Centre animal center provides, the quality certification number:
Experimental technique:
90 of mices are divided into 9 groups at random, 10 every group, are respectively normal group, model group, bifendate matched group, the high, medium and low dosage group of silybin meglumine tablets and the high, medium and low dosage group of silybin meglumine freeze-dried powder.
Bifendate drop pill and silybin meglumine tablets are made into the suspension of respective concentration with distilled water, and the silybin meglumine freeze-dried powder is made into respective concentration solution with the injection normal saline.Dosage 0.2ml/10g.
Normal group and model group mouse stomach are given distilled water, and each group of bifendate and silybin meglumine tablets is irritated the suspension that stomach gives relative medicine, and the silybin meglumine freeze-dried powder is respectively organized tail vein injection and given relative medicine, once a day, and successive administration 5 days.
After the administration in the 5th day, except that normal control group mice, each organizes the injection soybean oil solution that the equal lumbar injection of mice contains 0.1% carbon tetrachloride, 0.1ml/10g.Fasting immediately 16 hours, the eye socket blood sampling, separation of serum is measured GPT and GOT level.
Experimental result:
Table 1. silybin-N-methylglucamine tablet and lyophilized injectable powder are to CCl
4Cause the mouse liver injury protective effect relatively
| Group | Dosage (mg/kg) | ??GOT ??(U/L) | ????GPT ????(U/L) |
| Normal model DDB Silybin sheet Silybin sheet Silybin sheet Silybin powder pin Silybin powder pin Silybin powder pin | ????—— ????????—— ????????7.5 ????200 ????50 ????12.5 ????100 ????25 ????6.25 | ??11.8±4.9 ??115.2±61.8 ##??27.7±16.0 **??41.2±26.4 **??58.2±32.5 *??88.7±43.0 ??25.7±13.3 **??45.4±15.8 **??70.0±27.5 * | ????15.8±10.2 ????136.5-60.7 ##????28.3±15.9 **????46.3±22.4 **????72.2±33.0 **????107.5±38.9 ????29.7±18.7 **????60.6±33.1 **????90.3±30.6 * |
##, compare with normal group P＜0.01.
*, P＜0.05;
*, compare with model group P＜0.01.
Experimental result shows that therapeutic effect still obviously was better than the gastric infusion group when silybin meglumine drug administration by injection reduced by one times at dosage.
Test example 2: injection silybin meglumine lyophilized preparation and its tablet are to rat fulminant hepatic failure therapeutical effect comparative experiments material: silybin meglumine freeze-dried powder (Silybin powder pin), and press embodiment 1 and prepare, 50mg/ props up, lot number: 20030911.Silybin meglumine tablets (Silybin sheet), Jiangsu Zhongxing Pharmaceutical Co., Ltd. produces, 50mg/ sheet, lot number: 20030803.Bifendate drop pill, Dezhou, Shandong Province pharmaceutical factory produces, 1.5mg/ ball, lot number: 030205.Glutamic oxaloacetic transaminase, GOT (GOT) is measured test kit, lot number: 20030501, and glutamate pyruvate transaminase (GPT) is measured test kit, lot number: 20030602, reitman-frankel method is measured, and Shanghai Rongsheng Bioisystech Co., Ltd produces.Thioacetamide (TAA), the Sigma product.Animal: the Wistar rat, male, body weight 150 ~ 180g, Shandong Province's natural drug Engineering Technical Research Centre animal center provides, the quality certification number:
Experimental technique:
60 of rats, be divided into 5 groups at random, every group 10, be respectively normal group, model group, silybin meglumine tablets height (100mg/kg), low (25mg/kg) dosage group and silybin meglumine freeze-dried powder height (50mg/kg), low (12.5mg/kg) dosage group.
Bifendate drop pill and silybin meglumine tablets are made into the suspension of respective concentration with distilled water, and the silybin meglumine freeze-dried powder is made into respective concentration solution with the injection normal saline.Dosage 0.2ml/10g.
Model group and administration group rat skin lower injection TAA 600mg/kg 2 times, 24 hours at interval, normal rats was given the equivalent normal saline, after last gives TAA, gives relative medicine immediately, silybin meglumine tablets agent gastric infusion, freeze dried powder tail intravenously administrable.After 6 hours, each organizes the blood sampling of rat eye socket, and separation of serum is measured GPT and GOT level.
Experimental result:
Table 2. silybin-N-methylglucamine tablet and lyophilized injectable powder compare the protective effect that TAA causes rats'liver depletion
| Group | Dosage (mg/kg) | ??GOT ??(U/L) | ??GPT ??(U/L) |
| Normal model Silybin sheet Silybin sheet Silybin powder pin Silybin powder pin | ????—— ????????—— ????????100 ????25 ????50 ????12.5 | ??4.6±3.6 ??409.0±66.8 ##??365.9±56.9 ??377.3±64.5 ??292.3±68.2 *??339.7±64.5 * | ??4.6±3.6 ??500.1±134.9 ##??444.9±106.4 ??487.8±113.9 ??330.7±95.9 **??387.6±87.9 * |
##, compare with normal group P＜0.01.
*, P＜0.05;
*, compare with model group P＜0.01.
The result shows (seeing Table 2), and each dosage group of silybin meglumine freeze dried powder causes GOT after the rat acute liver failure and GPT to TAA and raises certain protective action is arranged, and the silybin meglumine tablets agent is not showing therapeutical effect under the high dose more yet.Illustrate that the silybin-N-methylglucamine drug administration by injection is better than oral administration to the therapeutic effect of acute severe liver injury.
Claims (10)
1. silibinin salt freeze-dried powder is characterised in that and contains PH regulator, solubilizing agent or its combination.
2. freeze-dried powder according to claim 1, silibinin salt can be silibinin inorganic base salts, the organic alkali salt of silibinin or silibinin amino acid salts; The silibinin inorganic base salts is selected from: silibinin sodium salt, silibinin potassium salt, silibinin ammonium salt; The organic alkali salt of silibinin is selected from: silybin-N-methylglucamine, silibinin amine salt; The silibinin amino acid salts is selected from: silibinin arginine salt, silibinin lysinate.
3. freeze-dried powder according to claim 2, silibinin salt is preferably silybin meglumine.
4. according to the arbitrary described freeze-dried powder of claim 1-3, the PH regulator is selected from one or more in sodium hydroxide, potassium hydroxide, meglumine, sodium carbonate, the potassium carbonate; Solubilizing agent is selected from one or more in 2-HP-, beta-schardinger dextrin-, sulfobutyl ether-beta-schardinger dextrin-, alpha-cyclodextrin, gamma-cyclodextrin, polyvinylpyrrolidone, the Polyethylene Glycol.
5. according to the arbitrary described freeze-dried powder of claim 1-3, be characterised in that its pH value of aqueous solution is 7-12 when adding water to freeze-dried powder with the lyophilized powder equal-volume.
6. according to the described freeze-dried powder of claim 1-3, it can also contain in excipient, antioxidant, the complexing of metal ion agent one or more.
7. freeze-dried powder according to claim 6, excipient is selected from one or more in mannitol, sucrose, lactose, arginine, lysine, glycine, sorbitol, the low molecular dextran; Antioxidant is selected from one or more in sodium thiosulfate, sodium sulfite, thiourea, the vitamin C; The complexing of metal ion agent is selected from one or more among EDTA-4Na, EDTA-2Na, the EDTA.
8. the preparation method of the arbitrary described freeze-dried powder of claim 1-7, form by following steps:
(1) prepares the aqueous solution that contains solubilizing agent in proportion;
(2) get the aqueous solution that silibinin salt places above-mentioned solubilizing agent in proportion, stir and make dissolving;
(3) regulating pH value with the pH regulator agent is 7-12;
(4) by requirement sterilization, the depyrogenation of injection, filtering with microporous membrane, packing;
(5) lyophilization.Lyophilization divided for three phases.The first phase, the quick freezing phase.Speed cooling with per minute 1-10 ℃ drops to-30 to-50 ℃ until solution temperature, keeps 2-5 hour; The second phase, the distillation phase (removing Free water).Evacuation makes vacuum between 50-500 μ bas, and temperature was kept 5-20 hour between-30 to-10 ℃; The third phase, the redrying phase (removing bound water).Vacuum remains on 50-500 μ bas, and temperature remains on 0-50 ℃, and this process was kept 2 to 10 hours.
(6) vacuum tamponade, promptly.
9. according to the preparation method of the arbitrary described silibinin salt lyophilized preparation of claim 1-7, be characterised in that:
(1) get silibinin salt in proportion and place aqueous solution, regulating pH value with the pH regulator agent is 10-12;
(2) by requirement sterilization, the depyrogenation of injection, filtering with microporous membrane, packing;
(3) lyophilization.Lyophilization divided for three phases.The first phase, the quick freezing phase.Speed cooling with per minute 1-10 ℃ drops to-30 to-50 ℃ until solution temperature, keeps 2-5 hour; The second phase, the distillation phase (removing Free water).Evacuation makes vacuum between 50-500 μ bas, and temperature was kept 5-20 hour between-30 to-10 ℃; The third phase, the redrying phase (removing bound water).Vacuum remains on 50-500 μ bas, and temperature remains on 0-50 ℃, and this process was kept 2 to 10 hours.
10. the preparation method of the arbitrary described freeze-dried powder of claim 1-7, form by following steps:
(1) prepares the aqueous solution that contains solubilizing agent in proportion;
(2) get the aqueous solution that silibinin salt places above-mentioned solubilizing agent in proportion, stir and make dissolving;
(3) by requirement sterilization, the depyrogenation of injection, filtering with microporous membrane, packing;
(4) lyophilization.Lyophilization divided for three phases.The first phase, the quick freezing phase.Speed cooling with per minute 1-10 ℃ drops to-30 to-50 ℃ until solution temperature, keeps 2-5 hour; The second phase, the distillation phase (removing Free water).Evacuation makes vacuum between 50-500 μ bas, and temperature was kept 5-20 hour between-30 to-10 ℃; The third phase, the redrying phase (removing bound water).Vacuum remains on 50-500 μ bas, and temperature remains on 0-50 ℃, and this process was kept 2 to 10 hours.
(5) vacuum tamponade, promptly.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 200410023873 CN1679542A (en) | 2004-04-06 | 2004-04-06 | Frozen powder injection of silybin and its preparing method |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 200410023873 CN1679542A (en) | 2004-04-06 | 2004-04-06 | Frozen powder injection of silybin and its preparing method |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN1679542A true CN1679542A (en) | 2005-10-12 |
Family
ID=35066565
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN 200410023873 Pending CN1679542A (en) | 2004-04-06 | 2004-04-06 | Frozen powder injection of silybin and its preparing method |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN1679542A (en) |
Cited By (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN100382799C (en) * | 2005-07-06 | 2008-04-23 | 鲁南制药集团股份有限公司 | Power for intravenous injection with liver-protecting action, and its preparation and quality control method |
| CN101244041B (en) * | 2007-02-13 | 2011-04-06 | 广州安健实业发展有限公司 | Medicament for preventing and treating acute liver damnification and preparation thereof |
| WO2011104667A1 (en) * | 2010-02-25 | 2011-09-01 | Anthem Biosciences Private Limited | Basic aminoacid salts of polyphenols |
| CN103494801A (en) * | 2013-09-29 | 2014-01-08 | 中国药科大学 | Action mechanism of silybin for preventing liver apoptosis through FXR (Farnesoid X Receptor) path |
| WO2016110193A1 (en) * | 2015-01-05 | 2016-07-14 | 天士力制药集团股份有限公司 | Silybin injection and preparation method therefor |
| JP2018510220A (en) * | 2015-03-19 | 2018-04-12 | サイデックス・ファーマシューティカルズ・インコーポレイテッド | Compositions containing silymarin and sulfoalkyl ether cyclodextrins and methods of using the same |
| CN111214446A (en) * | 2020-03-07 | 2020-06-02 | 瑞阳制药有限公司 | Peruvir L-arginine salt freeze-dried preparation for injection |
| CN114569538A (en) * | 2021-03-31 | 2022-06-03 | 南京宸翔医药研究有限责任公司 | Novel high-purity silybin meglumine pharmaceutical preparation as well as preparation method and application thereof |
-
2004
- 2004-04-06 CN CN 200410023873 patent/CN1679542A/en active Pending
Cited By (14)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN100382799C (en) * | 2005-07-06 | 2008-04-23 | 鲁南制药集团股份有限公司 | Power for intravenous injection with liver-protecting action, and its preparation and quality control method |
| CN101244041B (en) * | 2007-02-13 | 2011-04-06 | 广州安健实业发展有限公司 | Medicament for preventing and treating acute liver damnification and preparation thereof |
| WO2011104667A1 (en) * | 2010-02-25 | 2011-09-01 | Anthem Biosciences Private Limited | Basic aminoacid salts of polyphenols |
| CN103494801A (en) * | 2013-09-29 | 2014-01-08 | 中国药科大学 | Action mechanism of silybin for preventing liver apoptosis through FXR (Farnesoid X Receptor) path |
| US10314923B2 (en) | 2015-01-05 | 2019-06-11 | Tasly Pharmaceutical Group Co., Ltd. | Silybin injection and preparation method therefor |
| WO2016110193A1 (en) * | 2015-01-05 | 2016-07-14 | 天士力制药集团股份有限公司 | Silybin injection and preparation method therefor |
| RU2712264C2 (en) * | 2015-01-05 | 2020-01-28 | Тасли Фармасьютикал Груп Ко., Лтд. | Composition for silybin-based injections and method for production thereof |
| TWI684451B (en) * | 2015-01-05 | 2020-02-11 | 大陸商天士力醫藥集團股份有限公司 | Silybin injection and its preparation method |
| JP2018510220A (en) * | 2015-03-19 | 2018-04-12 | サイデックス・ファーマシューティカルズ・インコーポレイテッド | Compositions containing silymarin and sulfoalkyl ether cyclodextrins and methods of using the same |
| US10702568B2 (en) | 2015-03-19 | 2020-07-07 | Cydex Pharmaceuticals, Inc. | Compositions containing silymarin and sulfoalkyl ether cyclodextrin and methods of using the same |
| US11382944B2 (en) | 2015-03-19 | 2022-07-12 | Cydex Pharmaceuticals, Inc. | Compositions containing silymarin and sulfoalkyl ether cyclodextrin and methods of using the same |
| CN111214446A (en) * | 2020-03-07 | 2020-06-02 | 瑞阳制药有限公司 | Peruvir L-arginine salt freeze-dried preparation for injection |
| CN111214446B (en) * | 2020-03-07 | 2022-02-25 | 瑞阳制药股份有限公司 | Peruvir L-arginine salt freeze-dried preparation for injection |
| CN114569538A (en) * | 2021-03-31 | 2022-06-03 | 南京宸翔医药研究有限责任公司 | Novel high-purity silybin meglumine pharmaceutical preparation as well as preparation method and application thereof |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN106074465A (en) | Cannabinol compounds application in preparation treatment gouty arthritis medicine | |
| CA2494157C (en) | Inclusion complexes of butylphthalide with cyclodextrin or its derivatives, a process for their preparation and the use thereof | |
| CN1679542A (en) | Frozen powder injection of silybin and its preparing method | |
| NO343552B1 (en) | Compositions for the treatment of chronic degenerative inflammatory conditions | |
| KR101468153B1 (en) | 5α-ANDROSTANE-3β,5,6β-TRIOL INJECTION AND PREPARATION METHOD THEREFOR | |
| CN106074463A (en) | Cannabidiol application in preparation treatment gouty arthritis medicine | |
| CN1823768A (en) | Cimetidine freeze dried composition | |
| US11141382B2 (en) | Sintered nanoparticles and use of the same against a virus | |
| CN1259041C (en) | Bromhexine Hydrochloride aseptic freeze-drying formulation for injection and its preparation method | |
| TWI605821B (en) | A use of an extract of asplenium australasicum (j. sm.) hook. | |
| KR20170077300A (en) | pharmaceutical composition for preventing and treating kidney disease use gallic extract, health functional food composition | |
| CN1209104C (en) | Neohouttuynin sodium freeze-dried powder-injection, and its prepn. method | |
| CN103301118A (en) | Arginine ibuprofen composition for injection | |
| CN1839822A (en) | Injectable stable pharmaceutical composition containing active ingredient silibinin and its salt | |
| CN1565465A (en) | Injection preparation containing breviscapine active component and its preparation method | |
| CN1899329A (en) | Medicinal composition with blood fat reducing function | |
| JP5376786B2 (en) | Nerve cell activation composition | |
| CN1850097A (en) | Scutellarin injection preparation and its preparing method | |
| CN1555806A (en) | Paeonoside injection and its preparation method and use | |
| CN1157824A (en) | Azrinomycin dihydric phosphate complex salt and its preparation | |
| CN103845311A (en) | New medical use of resveratrol | |
| CN1391899A (en) | Aseptic freeze-dried prostaglandin injection and its preparing method and use | |
| CN1233327C (en) | Highly effective sustained release breviscapine compositions and its granule capsule | |
| IT9022342A1 (en) | FORMULATIONS OF LYOPHILIZED AMINO ACIDS CONTAINING GLUTAMINE, THEIR PREPARATION AND USE IN THE PARENTERAL FEEDING | |
| JP2009084207A (en) | Pharmaceutical composition |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C02 | Deemed withdrawal of patent application after publication (patent law 2001) | ||
| WD01 | Invention patent application deemed withdrawn after publication |