WO2012146057A1 - Solution d'injection de curcuminoïdes et injection intraveineuse de curcuminoïdes - Google Patents

Solution d'injection de curcuminoïdes et injection intraveineuse de curcuminoïdes Download PDF

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WO2012146057A1
WO2012146057A1 PCT/CN2012/000546 CN2012000546W WO2012146057A1 WO 2012146057 A1 WO2012146057 A1 WO 2012146057A1 CN 2012000546 W CN2012000546 W CN 2012000546W WO 2012146057 A1 WO2012146057 A1 WO 2012146057A1
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curcumin
injection
emulsion
injection solution
preparation
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PCT/CN2012/000546
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English (en)
Chinese (zh)
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陈建明
揭继龙
张广军
刘文丽
净小龙
连建豪
张莹莹
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中国人民解放军第二军医大学
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Publication of WO2012146057A1 publication Critical patent/WO2012146057A1/fr

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/12—Ketones
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
    • A61K47/10—Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/0019—Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/08—Solutions
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/16—Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/06—Antihyperlipidemics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P39/00—General protective or antinoxious agents
    • A61P39/06—Free radical scavengers or antioxidants
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P7/00—Drugs for disorders of the blood or the extracellular fluid
    • A61P7/02—Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis

Definitions

  • the invention relates to the technical field of medicine, and relates to a curcumin compound injection solution and an intravenous injection thereof. Background technique
  • Curcumin compounds are a chemical component extracted from the rhizomes of some plants in the family Zingiberaceae and Araceae, including curcumin, demethoxycurcumin, and bis-methoxycurcumin.
  • the curcuminoid compound is insoluble in water and diethyl ether and is soluble in methanol, ethanol, acetone, ethyl acetate, glacial acetic acid and lye. Unstable in light and alkaline environments, keep away from light.
  • curcuminoids The main pharmacological effects of curcuminoids are anti-oxidation, anti-inflammatory, anti-coagulation, lipid-lowering, anti-atherosclerosis, anti-aging, free radical elimination and tumor growth inhibition, and have liver-preserving effects.
  • curcumin due to the poor water solubility of curcumin, the bioavailability is low when taken orally, and the stability in vitro is poor (Zhong Mingyuan et al., Progress in the preparation of curcumin [J]. Chinese Traditional Medicine, 2007, 29 (2): 255-258). Therefore, curcumin is used as an injection for liposomes, nanoparticles, ⁇ -cyclodextrin inclusions, microspheres, microemulsions, etc., to improve the bioavailability and drug stability of curcuminoids.
  • these injections still have the following disadvantages:
  • Curcumin liposome Li Liping et al. (Study on the preparation technology of curcumin liposome[J]. Journal of the Fourth Military Medical University, 2009, 30(24 ) : 3166-3168 ), which is made by using ethanol injection method to make curcumin
  • the average encapsulation efficiency of the plastid is only 46.69%, the encapsulation efficiency is low, and the steps such as water bath and rotary steaming are required to be operated for a long time, and industrial production is difficult to be realized;
  • Curcumin nanoparticles Liu Zhanjun et al. (Preparation and drug release properties of curcumin nanoparticles] [J].
  • Chinese medicinal materials, 2009.32 (2): 277-279 ) the drug loading of curcumin nanoparticles is 0.3 g / liter
  • the encapsulation efficiency was up to 91.6%, but with the increase of curcumin drug concentration, the encapsulation efficiency was only 79.4% when the drug loading was 0.6 g/L, and the encapsulation efficiency decreased with the increase of drug concentration. Poor drug-forming properties, water bath, magnetic stirring, dialysis, long operation time and complicated operation steps are used in the preparation process;
  • the present invention provides a curcumin compound injection solution which is simple in preparation method, good in stability, large in drug loading amount, and low in toxic and side effects, and an intravenous injection preparation thereof as a curcumin compound.
  • the curcumin compound intravenous injection of the present invention comprises a curcumin compound injection solution and an emulsion.
  • composition and composition of the curcumin compound injection solution of the invention are as follows:
  • Curcumin compound 0.1% ⁇ 8% preferably 1% ⁇ 6%
  • pH adjuster adjust the pH to 2.5 ⁇ 6.98, preferably pH3.0 ⁇ 4.5
  • Antioxidant 0 ⁇ 4.0%
  • the curcumin compound is selected from one or more of curcumin, demethoxycurcumin, and bis-demethoxycurcumin;
  • the pH adjusting agent is selected from one or more of citric acid, malic acid, tartaric acid, acetic acid, lactic acid, phosphoric acid, triethanolamine, hydrochloric acid, sodium carbonate, sodium hydrogencarbonate, sodium hydroxide; preferably citric acid;
  • the solvent for injection is selected from one or more of polyethylene glycol 200, polyethylene glycol 300, polyethylene glycol 400, propylene glycol, glycerin, absolute ethanol, dimethylacetamide; preferably polyethyl b. Glycol 400;
  • the chelating agent is disodium ethylenediaminetetraacetate
  • the antioxidant is tocopherol (vitamin E), tert-butyl p-hydroxyanisole (BHA), 2,6-di-tert-butyl-p-cresol (BHT) , one or more of tert-butyl hydroquinone (TBHQ), L-cysteine, glutathione, phospholipid, propyl gallate.
  • phospholipids act as antioxidants and also act as solubilizers.
  • the preparation method of the injection solution of the invention is as follows - the curcumin compound is taken into a suitable amount of the injection solvent according to the ratio, stirred or sheared and dissolved at 20 to 100 C, and the chelating agent and the antioxidant are added according to the ratio, and the solvent for injection is used. Allow sufficient amount, adjust pH with pH adjuster; then add activated carbon to the needle, add 0.02% ⁇ 1% g/ml, adsorb 15 ⁇ 60 at heating temperature of 25 ⁇ 100 °C After filtering in minutes, the filtrate can be dispensed, sealed, and sterilized.
  • the preparation method of the curcumin compound intravenous injection according to the present invention is as follows - the curcumin compound injection solution and the emulsion are mixed in a ratio of 1:5 to 250 before use, and the preferred mixing ratio is 1: 10 ⁇ 100, which is an intravenous injection of curcuminoids.
  • the emulsion may be a commercially available emulsion or may be prepared by a prior art, and may be an emulsion such as a medium/long-chain fat emulsion injection, a fat emulsion injection or a structural fat emulsion injection.
  • the curcumin compound injection solution and the emulsion are mixed, the curcumin compound can be loaded in an intravenous injection amount of up to 1.5 mg/ml, and does not crystallize out within 18 hours, showing strong stability.
  • the curcumin compound injection solution of the present invention may be packaged separately or in combination with an emulsion.
  • the combination package is based on the difference in the volume ratio of the curcumin compound injection solution and the emulsion.
  • the curcumin compound injection solution and the emulsion are separately packaged, and then packaged together, which can be a packaging unit of the curcumin compound injection solution. Packed together with a package of emulsions, such as a large bottle of emulsion and a small bottle of curcumin injection solution, or a plurality of packaging units of curcumin injection solution and one or more packaging units
  • the emulsion combination is packaged together. Mix in the required proportions at the time of use to prevent the precipitation of the curcuminoids during storage. When combining packaging, it is advisable to pack in one use.
  • the self-made emulsion of the present invention is as follows:
  • Emulsifier 0.5 ⁇ 5°/.
  • Isotonicity regulator appropriate amount, adjusted to be isotonic with the human body
  • pH adjuster Adjust pH to 4.0 ⁇ 9.0, preferably pH 6.5 ⁇ 8.5
  • the oil for injection is selected from the group consisting of caprylic acid monoglyceride, caprylic acid diglyceride, caprylic acid triglyceride, caprylic acid monoglyceride, caprylic acid diglyceride, caprylic acid triglyceride, capric acid monoglyceride, anthraquinone.
  • the emulsifier is selected from the group consisting of soybean phospholipid, egg yolk phospholipid, oleic acid, poloxamer 188, sodium cholate, preferably soybean phospholipid, egg yolk phospholipid;
  • the isotonicity adjusting agent is one or more selected from the group consisting of glucose, sodium chloride, glycerin, sorbitol, and mannitol, preferably glycerin;
  • the pH adjusting agent is selected from one or more of citric acid, hydrochloric acid, sodium carbonate, sodium hydrogencarbonate, and sodium hydroxide, preferably sodium hydroxide or hydrochloric acid.
  • the preparation method of the emulsion is:
  • an appropriate amount of isotonicity adjusting agent and an appropriate amount of emulsifier are added to the water for injection, and heated to 50 to 90 ° C to dissolve and dissolve to obtain an aqueous phase;
  • the oil phase and the aqueous phase are mixed at 50 to 90 ° C, emulsified or emulsified by a shearing emulsifier for 5 to 60 minutes, and the rotation speed is 5000 to 30000 rpm, to obtain colostrum; the colostrum is further emulsified, and then used
  • the volume of water for injection is adjusted to a constant volume, and the pH is adjusted with a pH adjuster.
  • the membrane is filtered through a microporous membrane, and the filtrate is divided into nitrogen, capped, and sterilized.
  • the preparation of the emulsion comprises dissolving the emulsifier in the injectable oil or dissolving the emulsifier in water.
  • the emulsification of the colostrum is carried out by a high pressure homogenizer at a pressure of 5000 to 25,000 psi.
  • the disinfection in the preparation step of the emulsion is sterilized by using a rotary high-pressure steam sterilization pot, circulating steam, etc., wherein the high temperature sterilization temperature is 100 to 12 rc, and the time is 25 to 60 minutes.
  • the filtration device in the preparation step of the emulsion includes, but is not limited to, a microporous membrane, a sand filter rod, a funnel or a capsule filter.
  • the emulsion is a white or off-white emulsion liquid having an average particle size of 50 to 500 nm and a pH of 4.0 to 9.0.
  • the drug loading is high, and the injection amount of the curcumin compound injection solution can be directly added to the emulsion.
  • the emulsion not only has a targeting effect as a drug carrier, but also provides nutritional supplement for tumor patients, thereby achieving a better therapeutic effect.
  • the curcumin compound injection solution of the invention does not contain any surfactant, intravenous injection The injection does not cause allergies and hemolysis, which provides a guarantee for the patient's medication safety.
  • the preparation process is simple.
  • the formulation of the preparation, especially the injection solution of curcumin compound, is simple in formulation and fully industrialized.
  • the preparation method of the curcumin compound injection solution of the invention is simple and safe, has good solution stability, is convenient for storage and transportation, and the curcumin compound intravenous injection uses emulsion as a dispersion, has good stability, has no toxic and side effects, and has good protection. Liver effect.
  • the present invention solves the problem that the curcuminoid compound cannot be prepared into an intravenous injection for clinical use for a long time. detailed description
  • curcumin injection solution Take 5 g of curcumin, add to 90 ml of polyethylene glycol 400 solvent, stir to dissolve at 75 ° C, then dilute to 100 ml with polyethylene glycol 400, adjust the pH to 4.5 with appropriate amount of citric acid, add 0.48 g The needle was activated with activated carbon, 7 (adsorbed for 25 minutes under TC, and then filtered through a 0.45 ⁇ m microporous membrane. The filtrate was packed at 2 ml per bottle, capped, and then sterilized by high pressure steam at 105 ° C for 60 minutes. Curcumin injection solution.
  • the water for injection is quantified to 1000 ml, and then filtered with a 0.45 ⁇ m microporous membrane. The filtrate is packed in 100 ml per bottle, then filled with nitrogen, capped, and sterilized with high pressure steam for 121 minutes. Emulsion.
  • the emulsion particles were determined to have an average particle diameter of 236 nm and a pH of 7.58.
  • a package unit of curcumin injection solution and a package unit of emulsion are packaged together.
  • the curcumin injection solution When administered, the curcumin injection solution is mixed with the emulsion to be intravenously instilled. The same below.
  • Oil phase preparation 100 g of caprylic acid triglyceride for injection, 50 g of soybean oil, 10 g of eugenol oil, 10 g of linseed oil, 15 g of sea buckthorn oil, 5 g of zedoary turmeric oil, and sesame oil 10 g, mixed, placed in a water bath and heated to 68 ° C, stirred to dissolve, to obtain an oil phase;
  • methoxycurcumin Take 0.1 g of methoxycurcumin, add to a mixed solution of 58 ml of polyethylene glycol 400 and 2 ml of absolute ethanol and 25 ml of dimethylacetamide, add tocopherol 0.05 g, 20 ° C Stir and dissolve, then make up to 100 ml with polyethylene glycol 400, adjust the pH to 5.5 with hydrochloric acid and sodium hydroxide, add 0.26 g of needle with activated carbon, adsorb at 100 ° C for 15 minutes, then use 0.45 ⁇ micro The membrane was filtered, and the filtrate was packed in 5 ml portions, capped, and then sterilized by high pressure steam for 105 minutes to obtain a demethoxycurcumin injection solution.
  • oil phase 100 g of soybean oil for injection and 100 g of caprylic acid triglyceride are mixed, heated to 85 ⁇ in a water bath, and 10 g of soybean phospholipid for injection is added, and stirred to dissolve to obtain an oil phase;
  • Preparation of aqueous phase take 800 ml of water for injection, add 2 g of poloxamer, 22.5 g of glycerin, and heat to 85 ° C in a water bath, stir to dissolve, and obtain an aqueous phase;
  • Preparation of emulsion The oil phase and the aqueous phase are mixed at 90 ° C, emulsified by a shear emulsifier for 30 minutes (speed: 4000 rpm) to obtain colostrum, and the pH is adjusted to 8.50 with sodium hydroxide solution;
  • the colostrum is further emulsified by a high-pressure homogenizer (pressure 11000 psi), the water for injection is quantified to 1000 ml, filtered through a 0.45 ⁇ microporous membrane filter, and the filtrate is packed in 100 ml per bottle, then nitrogen-filled, glanded, and rotated.
  • the autoclave was sterilized at 105 ° C for 60 minutes to obtain an
  • the combined package is the same as in the second embodiment.
  • curcumin Take 4 g of curcumin, add to 75 ml of a mixture solution of propylene glycol and glycerin 10 ml, stir to dissolve at 100 ° C, let cool, then dilute to 100 ml with propylene glycol, adjust with lactic acid and sodium carbonate, sodium bicarbonate
  • the pH was 5.9, 1 gram of needle was added to the activated carbon, and the adsorption was carried out at 45 ° C for 45 minutes, and then filtered through a 0.45 ⁇ m microporous membrane filter, and the filtrate was dispensed in a milliliter per bottle, and the lid was pressed, and then the high pressure steam was passed. Sterilization for 30 minutes gave the curcumin injection solution.
  • the water for injection is quantified to 1000 ml, filtered through a 0.45 ⁇ m microporous membrane filter, and the filtrate is packed in 250 ml per bottle, then filled with nitrogen, capped, and rotary autoclave at 105 ° C.
  • the bacteria was obtained for 60 minutes.
  • the emulsion particles were determined to have an average particle diameter of 304 nm and a pH of 8.43.
  • the combined package is the same as in the first embodiment.
  • curcumin 4.5g add to 95ml of polyethylene glycol 200, stir at 70 ° C to dissolve, add 0.05 grams of tocopherol, 0.02 grams of disodium edetate, then set with polyethylene glycol 200
  • Capacitance to 100 ml adjust pH to 2.5 with phosphoric acid and tartaric acid, add 0.7 g of needle to activated carbon, adsorb at 60 25 for 25 minutes, then use 0.45 ⁇ m
  • the microporous membrane was filtered, and the filtrate was packed in 2 ml portions, capped, and then sterilized by high pressure steam at 115 ° C for 45 minutes to obtain a curcumin injection solution.
  • oil phase 200 g of structural triglyceride for injection is placed in a water bath and heated to 58 ° C, and 45 g of egg yolk phospholipid for injection is added, and stirred to dissolve to obtain an oil phase;
  • aqueous phase 580 ml of water for injection, 5 g of poloxamer, 22.5 g of glycerin, placed in a water bath and heated to 58 ° C, stirred to dissolve, to obtain an aqueous phase;
  • the amount of water for injection is quantified to 1000 ml, filtered with a 0.22 ⁇ microporous membrane, and the filtrate is packed in 250 ml per bottle, then filled with nitrogen, and capped, with a rotary autoclave 1 15 °C. Sterilize for 45 minutes to obtain an emulsion.
  • the emulsion fine particles were determined to have an average particle diameter of 50 nm and a pH of 7.43.
  • the combined package is the same as in the first embodiment.
  • curcumin injection Take 2.5 g of curcumin, add 60 ml of polyethylene glycol 400, 25 ml of propylene glycol in a mixed solution, stir to dissolve at 85 ° C, then make up to 100 ml with polyethylene glycol 400, add 0.02 g needle
  • the activated carbon was adsorbed at 35 ° C for 45 minutes, then filtered through a 0.45 ⁇ m microporous membrane filter, and the filtrate was dispensed in 4 ml portions, capped, and then sterilized by 105 Torr autoclave for 45 minutes to obtain curcumin injection. Solution.
  • oil phase 150 g of soybean oil for injection, 30 g of sesame oil, 15 g of Brucea javanica oil, 5 g of zedoary turmeric oil, and mixed in a water bath to 85 ° C, and 7 g of egg yolk phospholipid for injection. Stirring to dissolve, to obtain an oil phase;
  • oil phase 100 g of soybean oil for injection and 100 g of sunflower oil are mixed, placed in a water bath and heated to 50 ° C, and 12 g of soybean phospholipid for injection is added, and stirred to dissolve to obtain an oil phase;
  • the combined package is the same as in the first embodiment.
  • curcumin 3.75 g, add to 90 ml of propylene glycol mixed solvent, stir to dissolve at 72 ° C, then dilute to 100 ml with propylene glycol, adjust the pH to 4 with appropriate malic acid and triethanolamine, add 0.30 g
  • the needle was adsorbed by activated carbon, adsorbed for 20 minutes at 60 Torr, and then filtered through a 0.45 ⁇ m microporous membrane. The filtrate was packed in 4 ml portions, capped, and then sterilized by circulating steam at 100 ° C for 60 minutes to obtain curcumin. Inject the solution.
  • oil phase 25 g of ganoderma lucidum spore oil, 25 g of corn oil, 90 g of octanoic acid monoester, 30 g of octyl glyceride, 30 g of linseed oil, mixed, and heated to 72 ° C in a water bath. , stir and mix to obtain the oil phase;
  • the combined package is the same as in the first embodiment.
  • curcumin Take 3 g of curcumin, add to a mixed solution of 95 ml of dimethylacetamide, stir to dissolve under 40 Torr, then make up to 100 ml with dimethyl acetamide, add 0.2 g of needle with activated carbon, and adsorb under 55 5555 After a minute, it was filtered through a 0.45 ⁇ m microporous membrane filter, and the filtrate was dispensed in 5 ml portions, capped, and then sterilized by autoclaving at 121 ° C for 25 minutes to obtain a curcumin injection solution.
  • oil phase 100 g of soybean oil for injection, 100 g of glyceryl caprylate, 100 g of caprylic acid diglyceride, 5 g of egg yolk phospholipid, and placed in a water bath and heated to 70 ° C, stirred Dissolve to obtain an oil phase;
  • the combined package is the same as in the first embodiment.
  • curcumin Take 6 g of curcumin, add to a mixed solution of 90 ml of dimethylacetamide, stir to dissolve at 50 ° C, then make up to 100 ml with dimethyl acetamide, adjust the pH to 5.6 with appropriate amount of citric acid, add 0.5 g of the needle was activated with activated carbon, adsorbed for 50 minutes at 60 ° C, and then filtered through a 0.45 ⁇ microporous membrane, and the filtrate was 4 ml per bottle. The mixture was filled, capped, and then sterilized by autoclaving at 121 Torr for 30 minutes to obtain a curcumin injection solution.
  • oil phase 35 g of caprylic acid triglyceride for injection, 10 g of evening primrose oil, 10 g of sea buckthorn oil, and 145 g of soybean oil are mixed, placed in a water bath and heated to 50 ° C, and added to the injection. 25 g of soybean phospholipid, stirred and dissolved to obtain an oil phase;
  • the combined package is the same as in the first embodiment.
  • curcumin injection solution 8 g was added to a mixed solvent of 70 ml of polyethylene glycol 400 and 20 ml of propylene glycol, stirred and dissolved at 85 ° C, then made up to 100 ml with polyethylene glycol 400, and adjusted to pH 3.5 with citric acid.
  • oil phase 14 grams of Brucea javanica oil, 7 grams of coix seed oil, 5 grams of citric acid triglyceride, 15 grams of safflower seed oil, 3 grams of fish oil, 16 grams of corn oil, mixed, placed in a water bath Heating to 60 ° C, stirring until dissolved, to obtain an oil phase;
  • Nitrogen filling, gland, rotary high pressure after 100 ml dispensing The steam sterilizer was sterilized at 117 ° C for 40 minutes to obtain an emulsion.
  • the emulsion fine particles were determined to have an average particle diameter of 198 nm and a pH of 6.4.
  • a package unit of curcumin injection solution and two packaging unit emulsions are packaged together.
  • curcumin Take 0.5 g of curcumin, add to a mixed solvent of 65 ml of polyethylene glycol 400 and 20 ml of propylene glycol, stir to dissolve at 30 ° C, then dilute to 100 ml with polyethylene glycol 400, with malic acid and three Ethanolamine was adjusted to pH 6.98, 0.40 g of needle was added to the activated carbon, adsorbed at 25 for 60 minutes, and then filtered through a 0.45 ⁇ microporous membrane, and the filtrate was dispensed in 10 ml portions, capped, and then flow-through steam 10 (TC sterilization for 60 minutes, that is, the curcumin injection solution.
  • TC sterilization for 60 minutes
  • oil phase 5 grams of sesame oil for injection, 5 grams of ganoderma lucidum spore oil, 1.2 grams of oleic acid, mixed, placed in a water bath and heated to 65 ° C, 12 grams of egg yolk phospholipid, stirred to dissolve, to obtain oil phase ;
  • the combined package is the same as in the first embodiment.
  • curcumin Take 3 g of curcumin, add to 90 ml of polyethylene glycol 400, stir to dissolve at 55 ° C, then make up to 100 ml with polyethylene glycol 400, adjust the pH to 4.5 with citric acid, add 0.12 g needle It was adsorbed by activated carbon at 65 ° C for 45 minutes, then filtered through a 0.45 ⁇ microporous membrane filter, and then sterilized by 0.22 ⁇ microporous membrane filtration. According to 2 ml of each bottle, the turmeric was obtained by aseptic filling and glanding. Injection solution.
  • oil phase 40 grams of artemisia oil for injection, 75 grams of citric acid monoester, 75 grams of citric acid diglyceride, 20 g of citric acid triglyceride and 50 g of sunflower seed oil were mixed, heated to 80 ° C in a water bath, and 12 g of soybean phospholipid for injection was added, and stirred to dissolve to obtain an oil phase;
  • the combined package is the same as in the first embodiment.
  • curcumin 5 g of curcumin, added to a mixed solution of 75 ml of polyethylene glycol 400, 20 ml of dimethylacetamide, stirred and dissolved at 65 ° C, and then made up to 100 ml with polyethylene glycol 400, with lactic acid
  • the pH was adjusted to 3.0, 0.25 g of the needle was added with activated carbon, adsorbed at 5 CTC for 50 minutes, and then filtered through a 0.22 ⁇ microporous membrane.
  • the filtrate was dispensed in 2 ml portions, capped, and then sterilized by high pressure steam 115 Torr. For 40 minutes, the curcumin injection solution was obtained.
  • oil phase 10 g of caprylic acid diglyceride for injection, 10 g of caprylic acid monoglyceride, 10 g of caprylic acid diglyceride, 10 g of caprylic acid triglyceride, 10 g of fish oil, 30 g of sunflower oil, Mix 20 grams of zedoary turmeric oil, heat it to 75 ⁇ in a water bath, add 12 g of soy lecithin for injection, 0.1 g of oleic acid, stir to dissolve, and obtain an oil phase;
  • the combined package is the same as in the first embodiment.
  • curcumin Take 3 g of curcumin, add to a mixed solution of 60 ml of polyethylene glycol 400 and 25 ml of dimethylacetamide, stir to dissolve at 60 ° C, and then make up to 100 ml with polyethylene glycol 400.
  • the pH was adjusted to 4 with acetic acid, 0.48 g of the needle was added, and the activated carbon was adsorbed at 30 ° C for 60 minutes, and then filtered through a 0.45 ⁇ m microporous membrane.
  • the filtrate was packed in 4 ml portions, capped, and then subjected to high pressure. The steam was sterilized at 115 ° C for 45 minutes to obtain a curcumin injection solution.
  • oil phase 200 g of soybean oil for injection is placed in a water bath and heated to 70 Torr, and 12 g of soybean phospholipid for injection is added, and stirred to dissolve to obtain an oil phase;
  • the amount of water for injection is quantified to 1000 ml, and then filtered with a microporous membrane of 0.45 ⁇ , and the filtrate is packed in 100 ml of each bottle, then filled with nitrogen, and capped, with a rotary autoclave at 121 °C. Sterilize for 30 minutes to obtain an emulsion.
  • the emulsion fine particles were determined to have an average particle diameter of 220 nm and a pH of 5.60.
  • the combined package is the same as in the first embodiment.
  • curcumin injection solution Take 5 g of curcumin, add to 90 ml of polyethylene glycol 400 solvent, stir to dissolve at 75 ° C, then make up to 100 ml with polyethylene glycol 400, adjust the pH to 4 with appropriate amount of citric acid, add 0.3 g
  • the needle was adsorbed by activated carbon at 70 ° C for 25 minutes, and then filtered through a 0.45 ⁇ m microporous membrane. The filtrate was dispensed, capped, and then sterilized by high pressure steam at 105 ° C for 45 minutes to obtain a curcumin injection solution.
  • the curcumin injection solution can be packaged separately or in combination with a commercially available emulsion. At the time of administration, the curcumin injection solution and the commercially available emulsion are mixed in a desired volume ratio, and can be intravenously instilled. The same below.
  • curcumin injection solution Take 4 g of curcumin, add to 92 ml of polyethylene glycol 300, stir to dissolve at 80 ° C, then dilute to 100 ml with polyethylene glycol 300, adjust pH to 4 with citric acid, add 0.35 g Needle with activated carbon, at 65 °C After adsorption for 30 minutes, it was filtered through a 0.45 ⁇ m microporous membrane filter, and the filtrate was dispensed, capped, and then sterilized by high pressure steam at 115 ° C for 45 minutes to obtain a curcumin injection solution.
  • curcumin Take 8 g of curcumin, add to a mixed solution of 55 ml of propylene glycol, 20 ml of dimethylacetamide and 5 ml of glycerin, stir to dissolve at 65 ° C, then dilute to 100 ml with propylene glycol, adjust the pH with lactic acid. For 3.5, 0.1 g of needle was added with activated carbon, adsorbed at 45 ° C for 45 minutes, and then filtered through a 0.45 ⁇ microporous membrane. The filtrate was dispensed, capped, and then sterilized by high pressure steam 12 C for 30 minutes. Get curcumin injection solution.
  • curcumin injection solution Take 7 grams of curcumin, add to 85 ml of polyethylene glycol 200, 7 (dissolve under TC to dissolve, then dilute to 100 ml with polyethylene glycol 200, adjust pH to 3.5 with citric acid, add 0.45 g The needle was adsorbed by activated carbon at 75 V for 25 minutes, and then filtered through a 0.45 ⁇ m microporous membrane. The filtrate was dispensed, capped, and then sterilized by high pressure steam for 115 minutes to obtain a curcumin injection solution.
  • curcumin Take 5 grams of curcumin, add to 90 ml of polyethylene glycol 200, stir to dissolve at 72 ° C, then dilute to 100 ml with polyethylene glycol 200, adjust the pH to 4 with appropriate amount of malic acid and triethanolamine Add 0.30 g of the needle to the activated carbon, adsorb it under 90 Torr for 30 minutes, then filter with a 0.45 ⁇ microporous membrane, dispense the filtrate, cap, and then sterilize with circulating steam at 100 ° C for 60 minutes to obtain curcumin. Inject the solution.
  • curcumin injection solution Take 2.5 g of curcumin, add to a mixed solution of 65 ml of polyethylene glycol 400 and 25 ml of dimethylacetamide, stir and dissolve at 50 ° C, then dilute to 100 ml with polyethylene glycol 400, with appropriate amount
  • the pH of the citric acid was adjusted to 5.6, 0.5 g of the needle was added to the activated carbon, and the mixture was adsorbed at 30 ° C for 50 minutes, and then filtered through a 0.45 ⁇ m microporous membrane filter, and the filtrate was dispensed, capped, and then autoclaved for 30 minutes. , that is, the curcumin injection solution.
  • Example 26 Preparation of curcumin intravenous injection 2.5 g of curcumin was added to a mixed solvent of 60 ml of polyethylene glycol 400 and 25 ml of propylene glycol, stirred and dissolved at 85 ° C, then made up to 100 ml with polyethylene glycol 400, and adjusted to pH 3.5 with citric acid. 0.18 g of the needle was added and adsorbed by activated carbon at 80 Torr for 25 minutes, and then filtered through a 0.45 ⁇ m microporous membrane. The filtrate was dispensed, capped, and then sterilized by high pressure steam U0O for 50 minutes to obtain a curcumin injection solution.
  • curcumin injection solution Take 6 grams of curcumin, add 70 ml of polyethylene glycol 400 and 25 ml of propylene glycol in a mixed solvent, stir to dissolve at 95 ° C, then dilute to 100 ml with polyethylene glycol 400, adjust the pH with malic acid 4, 0.40 g of needle was added with activated carbon, adsorbed at 25 ° C for 60 minutes, and then filtered through a 0.45 ⁇ microporous membrane filter, the filtrate was dispensed, capped, and then sterilized with circulating steam 10 (TC for 60 minutes). , that is, the curcumin injection solution.
  • methoxycurcumin 3 g was taken, added to a mixed solution of 75 ml of polyethylene glycol 400 and 15 ml of dimethylacetamide, stirred and dissolved at 75 ° C, and then made up to 100 with polyethylene glycol 400.
  • ML adjust the pH to 4.5 with appropriate amount of citric acid, add 0.48 g of needle with activated carbon, adsorb at 70 ° C for 25 minutes, then filter with 0.45 ⁇ microporous membrane, dispense the filtrate and sterilize with high pressure steam 105 60 for 60 minutes. , that is, demethoxy curcumin injection solution, stored for use.
  • curcumin injection solution Take 4 grams of curcumin, add to a mixed solution of 65 ml of polyethylene glycol 400 and 25 ml of dimethylacetamide, 8 (dissolved in TC, then dilute to 100 ml with polyethylene glycol 400, with acetic acid Adjust the pH to 4.5, add 0.35 g of needle to the activated carbon, adsorb at 65 ° C for 30 minutes, then filter with 0.45 ⁇ microporous membrane, and then disperse the filtrate and sterilize it with high pressure steam at 115 ° C for 45 minutes.
  • the curcumin injection solution is stored for use.
  • curcumin 3.0g add to 80ml of polyethylene glycol 400 solution, stir and dissolve at 70 °C, add fertility Phenol 0.01g, adjusted to pH 4.5 with acetic acid, then made up to 100 ml with polyethylene glycol 400, added 0.35 g of needle with activated carbon, adsorbed at 70 ° C for 25 minutes, and then filtered with 0.45 ⁇ microporous membrane The filtrate was divided and sterilized by high pressure steam at 1 15 ° C for 45 minutes to obtain a curcumin injection solution, which was stored for use.
  • curcumin 4.0 g add to 80 ml of polyethylene glycol 400 solution, stir and dissolve at 70 ° C, add tocopherol 0.05g, adjust the P H to 5.5 with acetic acid, and then make up to 100 with polyethylene glycol 400
  • 0.40 g of needle was added to the activated carbon, adsorbed at 70 ° C for 25 minutes, and then filtered through a 0.45 ⁇ m microporous membrane. The filtrate was dispensed and sterilized by high pressure steam at 115 ° C for 45 minutes to obtain curcumin injection. Solution, store for use.
  • curcumin 3.5 g add to 80 ml of polyethylene glycol 400 solution, stir and dissolve at 70 ° C, add tert-butyl p-hydroxyanisole (BHA) O.Olg, adjust the pH to 4.5 with citric acid, and then use Polyethylene glycol 400 was made up to 100 ml, 0.45 g of needle was added to the activated carbon, and adsorbed at 70 ° C for 25 minutes, then filtered through a 0.45 ⁇ m microporous membrane, and the filtrate was dispensed and sterilized by high pressure steam 115 45 45 In minutes, the curcumin injection solution is stored and ready for use.
  • BHA tert-butyl p-hydroxyanisole
  • curcumin 4.1 g add to 80 ml of polyethylene glycol 400 solution, stir and dissolve at 70 ° C, add tert-butyl p-hydroxyanisole (BHA) 0.10g, adjust the pH to 5.0 with citric acid, and then use poly Glycol 400 was made up to 100 ml, 0.40 g of needle was added to the activated carbon, adsorbed at 70 Torr for 25 minutes, and then filtered through a 0.45 ⁇ microporous membrane. The filtrate was dispensed and sterilized by high pressure steam at 115 ° C for 45 minutes. , that is, the curcumin injection solution is stored and ready for use.
  • BHA tert-butyl p-hydroxyanisole
  • curcumin 4.0 g add to 80 ml of polyethylene glycol 400 solution, stir and dissolve at 65 ° C, add 2, 6 -di-tert-butyl-p-cresol (BHT) O.Olg, adjust the pH with citric acid 5.5, then make up to 100 ml with polyethylene glycol 400, add 0.40 g of needle with activated carbon, adsorb at 65 ° C for 30 minutes, then filter with 0.45 ⁇ microporous membrane, the filtrate is divided into high pressure steam After sterilizing for 115 minutes, the curcumin injection solution was obtained and stored for use.
  • BHT 2, 6 -di-tert-butyl-p-cresol
  • curcumin 3.5 g add to 80 ml of polyethylene glycol 400 solution, stir and dissolve at 65 °C, add 2,6-di-tert-butyl-p-cresol (BHT) 0.10g, adjust the pH to 5.5 with citric acid Then, make up to 100 ml with polyethylene glycol 400, add 0.40 g of needle to activated carbon, adsorb at 65 °C for 30 minutes, then filter with 0.45 ⁇ microporous membrane, and dispense the filtrate with high pressure steam. Sterilize at 115 ° C for 45 minutes, then obtain curcumin injection solution, store Stand by.
  • BHT 2,6-di-tert-butyl-p-cresol
  • curcumin 4.5 g add to 80 ml of polyethylene glycol 400 solution, stir and dissolve at 65 ° C, add tert-butyl hydroquinone (TBHQ) O.Olg, adjust the pH to 5.5 with citric acid, and then use Polyethylene glycol 400 was made up to 100 ml, 0.40 g of needle was added to the activated carbon, and adsorbed at 65 ° C for 30 minutes, then filtered through a 0.45 ⁇ microporous membrane, and the filtrate was dispensed and then subjected to high pressure steam U 5 °C. After sterilization for 45 minutes, the curcumin injection solution was obtained and stored for use.
  • TBHQ tert-butyl hydroquinone
  • curcumin 4.5g add to 80ml of polyethylene glycol 400 solution, stir and dissolve at 65 °C, add tert-butyl hydroquinone (TBHQ) 0.10g, adjust the pH to 5.5 with citric acid, and then use poly Glycol 400 was made up to 100 ml, 0.40 g of needle was added to the activated carbon, adsorbed at 65 ° C for 30 minutes, and then filtered through a 0.45 ⁇ microporous membrane. The filtrate was dispensed and sterilized by high pressure steam at 115 ° C. After 45 minutes, the curcumin injection solution was obtained and stored for use.
  • TBHQ tert-butyl hydroquinone
  • curcumin 4.0g add to 80ml of polyethylene glycol 400 solution, 7 (dissolved under TC, add L-cysteine 0.01g, adjust pH to 5.0 with citric acid, then use polyethylene glycol 400 To a volume of 100 ml, 0.40 g of needle was added to the activated carbon, adsorbed at 65 ° C for 30 minutes, and then filtered through a 0.45 ⁇ microporous membrane. The filtrate was dispensed and sterilized by high pressure steam at 115 ° C for 45 minutes. The curcumin injection solution is stored and ready for use.
  • curcumin 4.0 g add to 80 ml of polyethylene glycol 400 solution, stir and dissolve at 70 ° C, add L-cysteine 0.10 g, adjust the pH to 5.0 with citric acid, and then use polyethylene glycol 400 The volume was adjusted to 100 ml, 0.40 g of needle was added to the activated carbon, and the mixture was adsorbed at 65 ° C for 30 minutes, and then filtered through a 0.45 ⁇ m microporous membrane. The filtrate was dispensed and sterilized by high pressure steam at 115 ° C for 45 minutes. The curcumin injection solution is stored and ready for use.
  • curcumin injection solution Take 2.5 g of curcumin, add to 80 ml of polyethylene glycol 400 solution, stir and dissolve at 70 ° C, add glutathione 0.01 g, adjust the pH to 5.5 with citric acid, and then make up to volume with polyethylene glycol 400. To 100 ml, add 0.40 g of the needle to the activated carbon, adsorb at 65 ° C for 30 minutes, then filter with a 0.45 ⁇ microporous membrane, and dispense the filtrate and sterilize it with high pressure steam at 15 ° C for 45 minutes. The curcumin injection solution is stored for use.
  • curcumin Take 2.5 g of curcumin, add to 80 ml of polyethylene glycol 400 solution, stir and dissolve at 70 ° C, add 0.10 g of glutathione, adjust the pH to 5.5 with citric acid, and then make up to volume with polyethylene glycol 400. To 100 ml, add 0.40 The needle of gram was adsorbed by activated carbon at 65 ° C for 30 minutes, and then filtered with a 0.45 ⁇ m microporous membrane. The filtrate was dispensed and sterilized by high pressure steam at 115 ° C for 45 minutes to obtain a curcumin injection solution. use.
  • curcumin Take 2.5 g of curcumin, add to 80 ml of polyethylene glycol 400 solution, stir and dissolve at 70 ° C, add 0.01 g of lecithin, adjust the pH to 4.5 with citric acid, and then make up to 100 with polyethylene glycol 400.
  • 0.40 g of the needle to the activated carbon, adsorb at 65 30 for 30 minutes, and then filter with a 0.45 ⁇ microporous membrane. The filtrate was dispensed and sterilized by high pressure steam at 115 ° C for 45 minutes to obtain a curcumin injection solution. Store for use.
  • curcumin injection Take 2.5 g of curcumin, add to 80 ml of polyethylene glycol 400 solution, stir and dissolve under 70 Torr, add soybean phospholipid O. lg, adjust pH to 4.5 with citric acid, and then make up to 100 ml with polyethylene glycol 400. Add 0.40 g of needle to activated carbon, adsorb at 65 ° C for 30 minutes, then filter with 0.45 ⁇ microporous membrane, and then disperse the filtrate and sterilize it with high pressure steam at 15 ° C for 45 minutes to obtain curcumin injection. Solution, store for use.
  • curcumin Take 2.5 g of curcumin, add to 80 ml of polyethylene glycol 400 solution, stir and dissolve under 70 Torr, add lecithin 1.0 g, adjust the pH to 4.5 with citric acid, and then make up to 100 ml with polyethylene glycol 400. 0.40 g of the needle was added to the activated carbon, adsorbed at 65 ° C for 30 minutes, and then filtered through a 0.45 ⁇ m microporous membrane. The filtrate was dispensed and sterilized by high pressure steam at 115 ° C for 45 minutes to obtain a curcumin injection solution. Store for use.
  • curcumin injection solution Take 2.5 g of curcumin, add to 80 ml of polyethylene glycol 400 solution, stir and dissolve under 70 Torr, add 4.0 g of soybean phospholipid, adjust the pH to 4.5 with citric acid, and then make up to 100 ml with polyethylene glycol 400.
  • curcumin Take 8.0 g of curcumin, add to 80 ml of polyethylene glycol 400 solution, stir and dissolve at 70 ° C, add soybean phospholipid 4.0 g and propyl gallate 0.01 g, adjust the pH to 4.5 with citric acid, and then use polyethylene
  • the diol 400 was made up to 100 ml, 0.40 g of needle was added to the activated carbon, and adsorbed at 65 ° C for 30 minutes, and then filtered through a 0.45 ⁇ microporous membrane, and the filtrate was dispensed and sterilized by high pressure steam at 115 ° C. In minutes, the curcumin injection solution is stored and ready for use.
  • Example 48 Preparation of Curcumin Injection Solution Take curcumin 3.0 g, add to 80 ml of polyethylene glycol 400 solution, stir and dissolve at 70 ° C, add 0.01 g of propyl gallate, adjust the pH to 4.5 with acetic acid, and then dilute with polyethylene glycol 400 to 100 ml, 0.35 g of needle was added to the activated carbon, adsorbed at 70 ° C for 25 minutes, and then filtered through a 0.45 ⁇ m microporous membrane. The filtrate was dispensed and sterilized by high pressure steam U 5 ° C for 45 minutes to obtain turmeric. Inject the solution and store it for later use.
  • curcumin Take 2.5 g of curcumin, add to 80 ml of polyethylene glycol 400 solution, stir and dissolve at 70 ° C, add 0.05 g of propyl gallate, adjust the pH to 5.5 with citric acid, and then make up to volume with polyethylene glycol 400.
  • 0.40 g of needle was added to the activated carbon, adsorbed at 70 Torr for 25 minutes, and then filtered through a 0.45 ⁇ m microporous membrane. The filtrate was dispensed and sterilized by high pressure steam at 115 ° C for 45 minutes to obtain curcumin injection. Solution, store for use.
  • the curcumin injection solution and the emulsion were mixed at a volume ratio of 1:50, and the drug content, the particle size of the emulsion particles, and the pH change of the preparation were measured at different times.
  • the method of investigation is as follows: Take 2 ml of curcumin injection solution, add it to 100 ml of emulsion and mix it into intravenous injection; determine the intravenous injection at different times according to conventional high performance liquid chromatography, particle size analyzer and pH meter.
  • the drug content, particle size and pH value of the point; the drug content at 100 o'clock after mixing is 100%, and the drug content at other time points is the percentage of the content of the injection after filtration compared with the time content of 0.
  • the drug content before and after the intravenous injection is measured at each time point, that is, after measuring the drug content of the intravenous injection before filtration, the intravenous injection is filtered through a 0.22 ⁇ microporous membrane to remove the precipitated drug. Crystallization, and then determine the drug content in the filtrate, repeating the measurement at least twice at each time point to measure the change of the drug content in the two intravenous injections to evaluate whether the drug is precipitated, if the drug content in the intravenous injection before and after filtration When the ratio is lower than 98%, the system error range is considered as drug precipitation, and the average value of the test results is shown in Table 1 and Table 2.
  • Drug content 100 100.4 99.8 101.4 99.6 100 94.7 Emulsion particle size (nm) 260 265 262 263.5 261.2 267 298 pH 5.35 5.38 5.35 5.35 5.32 5.37 5.29
  • the curcumin injection solution and the emulsion are mixed at a volume of 1:50, and the drug content, the average particle size of the emulsion particles, and the pH change of the preparation at different time points are detected. .
  • Drug content 100 100.5 98.9 100.3 101.7 98.9 94.4 Emulsion particle size (nm) 250 252 250 255.4 249.7 253.4 262.5 pH 5.86 5.87 5.82 5.86 5.81 5.83 5.78
  • the drug content of the curcumin intravenously showed little change in the filtrate within 18 hours, indicating that no crystals of curcumin were precipitated; the particle size of the emulsion particles did not change significantly; the pH remained substantially constant. , indicating that curcumin intravenous injection has good stability within 18 hours. Therefore, the curcumin injection solution is mixed with the emulsion before clinical use, and the stability and drug loading amount fully satisfy the requirements for clinical use.
  • the drug-administered group, the positive control group and the model group were injected subcutaneously with 0.5% carbon tetrachloride peanut oil solution at 0.5 ml/100 g immediately after the last administration on the fifth day, resulting in acute liver injury.
  • about 1 ml of blood was taken from the eye, and centrifuged at 3500 r/min for 10 minutes. The content of ALT and AST in the serum was determined by an automatic biochemical analyzer.
  • curcumin Take 2.5 g of curcumin, add to 90 ml of polyethylene glycol 400, stir to dissolve under 70 Torr, then dilute to 100 ml with polyethylene glycol 400, and add 0.10 g (0.10% wt) of tocopherol or gallic acid.
  • Propyl ester with lemon The pH of the citric acid was adjusted to 7, and 0.35 g of the needle was added to the activated carbon, and the mixture was adsorbed at 65 ° C for 30 minutes, and then filtered through a 0.45 ⁇ m microporous membrane filter, and the filtrate was dispensed into a transparent injection bottle, and the nitrogen was protected by a gland. After sterilization in a pressure steam sterilizer (121 ° C, 15 min), take out and let it cool.
  • a pressure steam sterilizer 121 ° C, 15 min

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Abstract

L'invention concerne une solution d'injection de curcuminoïdes principalement composée de curcuminoïdes, un solvant utilisé pour l'injection et une petite quantité d'un agent d'ajustement du pH. L'invention concerne également une injection intraveineuse de curcuminoïdes qui mélange simplement la solution d'injection mentionnée ci-dessus avec une émulsion à un rapport en volume de 1:5 à 1:250. Après le mélange de la solution d'injection de curcuminoïdes et de l'émulsion, la charge en médicament du curcuminoïde dans l'injection intraveineuse peut atteindre 1,5 mg/mL et ne se cristallise pas ou ne se sépare pas pendant 18 heures.
PCT/CN2012/000546 2011-04-27 2012-04-23 Solution d'injection de curcuminoïdes et injection intraveineuse de curcuminoïdes WO2012146057A1 (fr)

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