CN102225048A - Curcumin compound injection and intravenous injection preparation thereof - Google Patents
Curcumin compound injection and intravenous injection preparation thereof Download PDFInfo
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Abstract
The invention relates to the technical field of medicine, and particularly relates to a curcumin compound injection and an intravenous injection preparation thereof. The curcumin compound injection mainly comprises a curcumin compound, a solvent for injection and a small amount of pH regulator. The curcumin compound intravenous injection preparation is used only by mixing the curcumin compound injection and an emulsifier in a volume ratio of (1:5)-(1:250). After the curcumin compound injection and the emulsifier are mixed, the drug loading rate of the curcumin compound in the intravenous injection preparation is up to 1.5 mg/ml, and no crystal is separated out within 18 hours. The curcumin compound injection provided by the invention has a simple and safe preparation method and good stability, and is convenient for storage and transportation. The curcumin compound intravenous injection preparation has good stability due to the use of the emulsifier as a carrier solvent, and has no toxic and adverse effects. The invention solves the problem that the curcumin compound can not be prepared into the intravenous injection preparation and applied in clinics for a long period of time.
Description
Technical field
The present invention relates to medical technical field, is a kind of curcumin chemical compounds injection solution and intravenous injection thereof.
Background technology
Curcumin (Curcumin) compounds is a kind of chemical constituent of extracting in some the plant rhizome from Zingiberaceae, Araeceae, comprises curcumin, demethoxycurcumin, bisdemethoxycurcumin etc.Water insoluble and the ether of curcumin chemical compounds is dissolved in methanol, ethanol, acetone, ethyl acetate, glacial acetic acid and the alkali liquor.Unstable in illumination and alkaline environment, keep in Dark Place.
The main pharmacological of curcumin chemical compounds has antioxidation, antiinflammatory, anticoagulant, blood fat reducing, atherosclerosis, defying age to eliminate free radical and suppresses tumor growth etc., and liver protective effect is arranged.But because the curcumin poorly water-soluble, bioavailability is low when oral, and vitro stability poor (Zhong Mingyuan etc., curcumin preparation is learned progress [J]. Chinese patent medicine, 2007,29 (2): 255-258).So someone makes curcumin injections such as liposome, nanoparticle, Benexate Hydrochloride, microsphere, microemulsion, to improve the bioavailability and the medicine stability of curcumin chemical compounds.But these injections still have the following disadvantages:
1. curcumin liposome, Li Liping etc. (Study on Preparation of curcumin liposome [J]. The Fourth Military Medical University's journal, 2009,30 (24): 3166-3168), its average envelop rate with alcohol injection system curcumin liposome only is 46.69%, envelop rate is low, and need water-bath, to revolve the step operating time such as steaming longer, is difficult for realizing suitability for industrialized production;
2. sustained-release micro-spheres, and Lin Mei etc. (preparation of curcumin microsphere and sustained release performance research [J]. Medical University Of Fujian's journal, 2010,44 (3): 178-181), envelop rate can only reach 15.6%-62.4%, poor operability;
3. curcumin nanoparticles, Liu Zhanjun etc. (preparation of curcumin nanoparticles and Release Performance [J]. Chinese crude drug, 2009.32 (2): 277-279), the drug loading of curcumin nanoparticles envelop rate when 0.3 grams per liter is up to 91.6%, but raising along with the curcumin drug level, envelop rate only is 79.4% when drug loading is 0.6 grams per liter, and envelop rate raises along with drug level and reduces, become the property of medicine poor, in preparation process, to use water-bath, magnetic agitation, dialysis, operating time is long, the operating procedure complexity;
4. Benexate Hydrochloride, Han Gang etc. (Study on Preparation of curcumin Benexate Hydrochloride [J]. Chinese crude drug, 2004,27 (12): 946-948), in the time of 25 ℃, shook 72 hours, recording the curcumin Cmax is 1.022mg/L, and drug loading is very low, and uses beta-schardinger dextrin-in the preparation process, beta-schardinger dextrin-has very strong hemolytic, particularly has than kidney tonifying toxicity.
Because all deficiencies that above-mentioned injection exists are so it is clinical not see that so far the curcumin chemical compounds injection is applied to.
Summary of the invention
The invention provides that a kind of preparation method is simple, good stability, drug loading is big, toxic and side effects is little curcumin chemical compounds injection solution, and be prepared into the curcumin chemical compounds intravenous injection with it.Curcumin chemical compounds intravenous injection of the present invention is made up of curcumin chemical compounds injection solution and Emulsion.
Curcumin chemical compounds injection solution component of the present invention and proportioning are as follows:
Said curcumin chemical compounds is selected from one or more in curcumin, demethoxycurcumin, the bisdemethoxycurcumin;
Said pH value regulator is selected from one or more in citric acid, malic acid, tartaric acid, acetic acid, lactic acid, phosphoric acid, triethanolamine, hydrochloric acid, sodium carbonate, sodium bicarbonate, the sodium hydroxide; Optimization citric acid;
Said solvent for injection is selected from one or more in Macrogol 200, Liquid Macrogol, PEG400, propylene glycol, glycerol, dehydrated alcohol, the dimethyl acetylamide; Preferred PEG400;
Said chelating agen is a disodiumedetate, and said antioxidant is tocopherol.
The preparation method of injection solution of the present invention is as follows:
Get curcumin chemical compounds to an amount of solvent for injection by proportioning, stir or shear dissolving down, add chelating agen and antioxidant, be settled to capacity, regulate pH value with the pH regulator agent with solvent for injection by proportioning at 20～100 ℃; Add needle-use activated carbon then, addition is 0.02%～1% grams per milliliter, adsorbs 15～60 minutes after-filtration under 25～100 ℃ heating-up temperature, with the filtrate packing, seal, sterilizing gets final product.
The said preparation method with the curcumin chemical compounds intravenous injection of the present invention is as follows:
With curcumin chemical compounds injection solution and Emulsion face with preceding be 1: 5～250 mixed by volume, preferred mixed proportion is 1: 10～100, the curcumin chemical compounds intravenous injection.Said Emulsion can be commercially available Emulsion, also can make by oneself by prior art, in can be/Emulsion such as long chain fat emulsion injection, fat emulsion injection or structural fatty emulsion injection.
After curcumin chemical compounds injection solution and Emulsion mixed, drug loading can be up to 1.5mg/ml in intravenous injection for curcumin chemical compounds, and can crystallization not separate out in 18 hours, has shown strong stability.
Curcumin chemical compounds injection solution of the present invention can be packed separately, also can with the Emulsion assembly packaging.Assembly packaging is the different of volume ratio when mixing with Emulsion according to the curcumin chemical compounds injection solution, after curcumin chemical compounds injection solution and Emulsion packed respectively, recombinant is packaging together, can for the Emulsion assembly packaging of the curcumin chemical compounds injection solution of a packing unit and a packing unit together, as one big bottle of Emulsion and a bottle curcumin chemical compounds injection solution assembly packaging together, also can be the curcumin chemical compounds injection solution of a plurality of packing units and one or more packing units the Emulsion assembly packaging together.Face the time spent again by required mixed, in storage process, separate out in case mix the back curcumin chemical compounds.During assembly packaging, be packaged as suitable with a use amount.
The present invention is said from antigalactic, and its component and proportioning are as follows:
Wherein, oil for injection is selected from one or more in hot capric acid monoglyceride, hot capric acid diglyceride, hot tricaprin, sad monoglyceride, sad dialycerides, sad triglyceride, capric acid monoglyceride, capric acid dialycerides, capric acid triglyceride, structural type triglyceride, fish oil, soybean oil, Semen Maydis oil, Ganoderma spore oil, Semen Coicis oil, Oleum Fructus Bruceae, Herba Artemisiae Annuae oil, Semen Lini oil, Oleum Helianthi, Radix Oenotherae erythrosepalae oil, Oleum Hippophae, Oleum Curcumae, safflower oil, Oleum sesami, the elemi thin oil, preferred hot tricaprin, soybean oil;
Emulsifying agent is selected from one or more in soybean phospholipid, egg yolk lecithin, oleic acid, poloxamer 188, the sodium cholate, preferred soybean phospholipid, egg yolk lecithin;
Isoosmotic adjusting agent is selected from one or more in glucose, sodium chloride, glycerol, sorbitol, the mannitol, preferably glycerine;
The pH regulator agent is selected from one or more in citric acid, hydrochloric acid, sodium carbonate, sodium bicarbonate, the sodium hydroxide, preferred sodium hydroxide, hydrochloric acid.
The preparation method of Emulsion is:
1. preparation oil phase:
With oil for injection and an amount of emulsifier, be heated to 50～90 ℃ by proportioning, stirring or shearing make emulsifiers dissolve, get oil phase;
2. preparation water:
By proportioning an amount of isoosmotic adjusting agent and an amount of emulsifying agent are added in the water for injection, be heated to 50～90 ℃ of stirring and dissolving, get water;
3. preparation Emulsion:
Oil phase and water are mixed down at 50～90 ℃, use emulsification pretreatment device emulsifying or stirring and emulsifying 5～60 minutes, rotating speed is 5000～30000 rev/mins, gets colostrum; With the further emulsifying of colostrum, use the water for injection standardize solution then, regulate pH with the pH regulator agent, use filtering with microporous membrane, get final product filling nitrogen, gland, sterilization after the filtrate packing.
Comprise in the preparation process of Emulsion generally speaking emulsifiers dissolve in oil for injection or emulsifiers dissolve in water.Wherein the further emulsifying of colostrum is to adopt high pressure homogenizer emulsifying, and pressure is 5000～25000psi.Sterilization in the preparation process of Emulsion is to adopt sterilizations such as rotating type high-pressure steam sterilization pot, flowing steam, and wherein the high temperature sterilize temperature is 100～121 ℃, 25～60 minutes time.Filtration device in the preparation process of Emulsion includes but not limited to microporous filter membrane, sand filtration rod, sintered filter funnel or bag type filter.Emulsion is white or off-white color emulsion liquid, and mean diameter is 50～500nm, and pH is 4.0～9.0.
Experiment showed, that curcumin chemical compounds intravenous injection of the present invention meets the clinical application requirement fully, its advantage is:
1. drug loading height, curcumin chemical compounds injection solution join directly that drug loading can reach 1.5mg/ml in the Emulsion.
2. good stability: adopt Emulsion to produce beyond thought effect, can improve the stability of curcumin chemical compounds intravenous injection greatly as dispersion liquid.
3. can make nutrient: Emulsion not only has targeting as pharmaceutical carrier, simultaneously for tumor patient provides nutritional supplementation, thereby reaches therapeutic effect better.
4. safety is good: do not contain any surfactant in the curcumin chemical compounds injection solution of the present invention, intravenous injection allergy, haemolysis can not occur, for patient's drug safety provides assurance.
5. easy and simple to handle: preparation technology is simple, this preparation in process for preparation, the particularly preparation of curcumin chemical compounds injection solution, formulation and technology is simple, can realize suitability for industrialized production fully.
Curcumin chemical compounds injection solution preparation method of the present invention is simple and safe, and stability of solution is good, is convenient to store and transportation, and the curcumin chemical compounds intravenous injection is dispersion liquid with Emulsion, good stability, and have no side effect, also have good liver protective effect.The invention solves for a long time curcumin chemical compounds can't be prepared into intravenous injection and be applied to a clinical difficult problem.
The specific embodiment
Now in conjunction with the embodiments, the present invention is described in detail.
Embodiment 1 preparation curcumin intravenous injection
1. prepare the curcumin injection solution:
Get curcumin 5 grams, join in 90 milliliters of PEG400 solvents, 75 ℃ of following stirring and dissolving are settled to 100 milliliters with PEG400 then, are 4.5 with an amount of Fructus Citri Limoniae acid for adjusting pH, add 0.48 gram needle-use activated carbon, 70 ℃ adsorbed 25 minutes down, used the filtering with microporous membrane of 0.45 μ m then, and filtrate is pressed every bottle of 2 milliliters of packing, gland, with 105 ℃ of sterilizations of high steam 60 minutes, promptly get the curcumin injection solution then.
2. preparation Emulsion:
(1) preparation oil phase: place water-bath to be heated to 80 ℃ injection soybean oil 100 grams and hot tricaprin 100 grams, stir and make dissolving, get oil phase;
(2) prepare water: get 650 milliliters of waters for injection, add injection soybean phospholipid 12 grams, glycerol 22.5 grams place water-bath to be heated to 80 ℃, stir and make dissolving, get water;
(3) preparation Emulsion: oil phase and water are mixed down for 80 ℃, and with emulsification pretreatment device emulsifying 5 minutes, rotating speed was 8000 rev/mins, gets colostrum, and regulating its pH with sodium hydroxide solution is 7.71; With colostrum with the further emulsifying of high pressure homogenizer (pressure 10000psi), water for injection is used the filtering with microporous membrane of 0.45 μ m then quantitatively to 1000 milliliters, and filtrate is filled nitrogen, gland after by every bottle of 100 milliliters of packing, with 121 ℃ of sterilizations of high steam 30 minutes, get Emulsion.After measured, the mean diameter of this Emulsion microgranule is 236nm, and pH is 7.58.
The curcumin injection solution of 1 packing unit and the Emulsion assembly packaging of 1 packing unit are in the same place.
During administration,, get final product intravenous drip with curcumin injection solution and Emulsion mixing.Down together.
Embodiment 2 preparation curcumin intravenous injections
1. the preparation of curcumin injection solution:
Get curcumin 5 grams, join in 90 milliliters the Liquid Macrogol, 80 ℃ of following stirring and dissolving are settled to 100 milliliters with Liquid Macrogol then, and regulating pH with acetic acid is 4.5, the needle-use activated carbon that adds 0.35 gram, 65 ℃ adsorbed 30 minutes down, used the filtering with microporous membrane of 0.45 μ m then, and filtrate is pressed every bottle of 2 milliliters of packing, gland, with 115 ℃ of sterilizations of high steam 45 minutes, promptly get the curcumin injection solution then.
2. the preparation of Emulsion
(1) oil phase preparation: with hot tricaprin 100 grams of injection, soybean oil 50 restrains, and pulls fragrant alkene oil 10 grams, Semen Lini oil 10 grams, and Oleum Hippophae 15 grams, Oleum Curcumae 5 restrains, and sees Oleum sesami 10 grams the moon, mixes, and places water-bath to be heated to 68 ℃, stirs and makes dissolving, gets oil phase;
(2) water preparation: get 450 milliliters of waters for injection, add egg yolk lecithin 12 grams, place water-bath to be heated to 68 ℃, stirring makes dissolving, adds sorbitol 30 grams, mannitol 20 grams, stirs and makes dissolving, gets water;
(3) preparation Emulsion: oil phase and water are mixed down for 68 ℃,, get colostrum with emulsification pretreatment device emulsifying 20 minutes (5000 rev/mins of rotating speeds); With colostrum with the further emulsifying of high pressure homogenizer (pressure 18000psi), regulating its pH with sodium hydroxide solution or hydrochloric acid solution is 8.3, water for injection is settled to 1000 milliliters, through 0.45 μ m filtering with microporous membrane, filtrate was filled nitrogen, gland, 115 ℃ of sterilizations of high steam after by every bottle of 250 milliliters of packing 45 minutes, Emulsion.After measured, the mean diameter of this Emulsion microgranule is 214nm, and pH is 8.10.
The curcumin injection solution of 5 packing units and the Emulsion assembly packaging of 1 packing unit are in the same place.
Embodiment 3 preparation demethoxycurcumin intravenous injections
1. the preparation of demethoxycurcumin injection solution:
Remove methoxyl group curcumin 0.1 gram, join in the mixed solution of dimethyl acetylamide of the dehydrated alcohol of 58 milliliters PEG400 and 2 milliliters and 25 milliliters, add tocopherol 0.05 gram, 20 ℃ of following stirring and dissolving, be settled to 100 milliliters with PEG400 then, regulating pH with hydrochloric acid and sodium hydroxide is 5.5, the needle-use activated carbon that adds 0.26 gram, 100 ℃ adsorbed 15 minutes down, use the filtering with microporous membrane of 0.45 μ m then, filtrate is pressed every bottle of 5 milliliters of packing, gland with 105 ℃ of sterilizations of high steam 60 minutes, promptly gets the demethoxycurcumin injection solution then.
2. the preparation of Emulsion:
(1) prepares oil phase: with injection soybean oil 100 grams, hot tricaprin 100 gram mixings, place water-bath to be heated to 85 ℃, add injection soybean phospholipid 10 grams, stir and make dissolving, get oil phase;
(2) preparation water: get 800 milliliters of waters for injection, add poloxamer 2 grams, glycerol 22.5 grams place water-bath to be heated to 85 ℃, stir and make dissolving, get water;
(3) preparation Emulsion: oil phase and water are mixed down for 90 ℃, with emulsification pretreatment device emulsifying 30 minutes (4000 rev/mins of rotating speeds), get colostrum, regulating its pH with sodium hydroxide solution is 8.50; With colostrum with the further emulsifying of high pressure homogenizer (pressure 11000psi), water for injection is quantitatively to 1000 milliliters, through the filtering with microporous membrane of 0.45 μ m, filtrate filled nitrogen, gland after by every bottle of 100 milliliters of packing, with 105 ℃ of sterilizations of rotating type high-pressure steam sterilization still 60 minutes, get Emulsion.After measured, the mean diameter of this Emulsion microgranule is 275nm, and pH is 8.25.
Assembly packaging is with embodiment 2.
Embodiment 4 preparation curcumin intravenous injections
1. the preparation of curcumin injection solution:
Get curcumin 4 grams, join in 75 milliliters the mixed solution of 10 milliliters of propylene glycol, glycerol, 100 ℃ of following stirring and dissolving are put cold, be settled to 100 milliliters with propylene glycol then, regulating pH with lactic acid and sodium carbonate, sodium bicarbonate is 5.9, adds the needle-use activated carbon of 1 gram, and 45 ℃ adsorbed 45 minutes down, use the filtering with microporous membrane of 0.45 μ m then, by every bottle of 1 milliliter of packing, gland, 121 ℃ of sterilizations of high steam are 30 minutes then, promptly get the curcumin injection solution with filtrate.
2. the preparation of Emulsion:
(1) prepares oil phase: with injection soybean oil 100 grams, hot tricaprin 100 gram mixings, place water-bath to be heated to 78 ℃, add injection soybean phospholipid 8 grams, stir and make dissolving, get oil phase;
(2) prepare water: get 750 milliliters of waters for injection, add poloxamer 4 grams, sodium cholate 0.2 gram, sodium chloride 9 grams place water-bath to be heated to 78 ℃, stir and make dissolving, get water;
(3) preparation Emulsion: oil phase and water are mixed down for 78 ℃, with emulsification pretreatment device emulsifying 10 minutes (5000 rev/mins of rotating speeds), get colostrum, regulating its pH with sodium hydroxide solution is 8.5; With the further emulsifying of high pressure homogenizer (pressure 16000psi), water for injection is quantitatively to 1000 milliliters, through the filtering with microporous membrane of 0.45 μ m with colostrum, filtrate is filled nitrogen, gland after by every bottle of 250 milliliters of packing, 105 ℃ of rotating type high-pressure steam sterilization stills were sterilized 60 minutes, got Emulsion.After measured, the mean diameter of this Emulsion microgranule is 304nm, and pH is 8.43.
Assembly packaging is with embodiment 1.
Embodiment 5 preparation curcumin intravenous injections
1. the preparation of curcumin injection solution:
Get curcumin 4.5 grams, join in 95 milliliters the Macrogol 200, stir under 70 ℃ and make dissolving, add 0.05 gram tocopherol, 0.02 gram disodiumedetate, be settled to 100 milliliters with Macrogol 200 then, with phosphoric acid, winestone acid for adjusting pH is 2.5, the needle-use activated carbon that adds 0.7 gram, 60 ℃ adsorbed 25 minutes down, use the filtering with microporous membrane of 0.45 μ m then, filtrate by every bottle of 2 milliliters of packing, gland, with 115 ℃ of sterilizations of high steam 45 minutes, is promptly got the curcumin injection solution then.
2. the preparation of Emulsion
(1) preparation of oil phase: with injection structural type triglyceride 200 grams, place water-bath to be heated to 58 ℃, add injection egg yolk lecithin 45 grams, stir and make dissolving, get oil phase;
(2) preparation water: get 580 milliliters of waters for injection, add poloxamer 5 grams, glycerol 22.5 grams place water-bath to be heated to 58 ℃, stir and make dissolving, get water;
(3) preparation Emulsion: oil phase and water are mixed down for 58 ℃, with emulsification pretreatment device emulsifying 30 minutes (5500 rev/mins of rotating speeds), get colostrum, regulating its pH with sodium hydroxide solution is 7.65; With colostrum with the further emulsifying of high pressure homogenizer (pressure 25000psi), water for injection is quantitatively to 1000 milliliters, with the filtering with microporous membrane of 0.22 μ m, filtrate is filled nitrogen, gland after by every bottle of 250 milliliters of packing, with 115 ℃ of sterilizations of rotating type high-pressure steam sterilization still 45 minutes, Emulsion.After measured, the mean diameter of this Emulsion microgranule is 50nm, and pH is 7.43.
Assembly packaging is with embodiment 1.
Embodiment 6 preparation curcumin intravenous injections
1. the preparation of curcumin injection solution
Get curcumin 2.5 grams, join in the mixed solution of 60 milliliters PEG400,25 milliliters of propylene glycol, 85 ℃ of following stirring and dissolving, be settled to 100 milliliters with PEG400 then, add the needle-use activated carbon of 0.02 gram, 35 ℃ adsorbed 45 minutes down, use the filtering with microporous membrane of 0.45 μ m then, filtrate by every bottle of 4 milliliters of packing, gland, is used 105 ℃ of high pressure steam sterilizations 45 minutes then, promptly get the curcumin injection solution.
2. the preparation of Emulsion:
(1) preparation oil phase: with injection soybean oil 150 gram, Oleum sesami 30 grams, Oleum Fructus Bruceae 15 grams, Oleum Curcumae 5 gram mixings, place water-bath to be heated to 85 ℃, add injection egg yolk lecithin 7 grams, stir and make dissolving, oil phase;
(2) preparation water: get water for injection 400ml, glycerol adding 23.5 grams, 2 gram poloxamers 188 place water-bath to be heated to 85 ℃, stir and make dissolving, get water;
(3) preparation Emulsion: oil phase and water are mixed down for 85 ℃, with emulsification pretreatment device emulsifying 20 minutes (6500 rev/mins of rotating speeds), get colostrum, regulating its pH with sodium hydroxide is 9.35; With colostrum with the further emulsifying of high pressure homogenizer (pressure 15000psi), water for injection is quantitatively to 1000 milliliters, through the filtering with microporous membrane of 0.45 μ m, filtrate filled nitrogen, gland after by every bottle of 100 milliliters of packing, with 100 ℃ of sterilizations of rotary steam Sterilization Kettle 60 minutes, get Emulsion.After measured, the mean diameter of this Emulsion microgranule is 350nm, and pH is 9.0.
Assembly packaging is with embodiment 1.
Embodiment 7 preparation bisdemethoxycurcumin intravenous injections
1. the preparation of bisdemethoxycurcumin injection solution:
Get bisdemethoxycurcumin 1 gram, join in 75 milliliters the Liquid Macrogol and 20 milliliters of Macrogol 200 mixed liquors, 70 ℃ of following stirring and dissolving, be settled to 100 milliliters with Liquid Macrogol then, with the Fructus Mali pumilae acid for adjusting pH is 3.0, the needle-use activated carbon that adds 0.32 gram, 85 ℃ adsorbed 20 minutes down, use the filtering with microporous membrane of 0.45 μ m then, 0.22 μ m filtering with microporous membrane, filtrate by every bottle of 2 milliliters of packing, gland, is used 115 ℃ of high pressure steam sterilizations 45 minutes then, promptly get the bisdemethoxycurcumin injection solution.
2. the preparation of Emulsion:
(1) preparation oil phase: with injection soybean oil 100 gram, Oleum Helianthi 100 gram mixings, place water-bath to be heated to 50 ℃, add injection soybean phospholipid 12 grams, stir and make dissolving, oil phase;
(2) preparation water: get 640 milliliters of waters for injection, add glucose 50 grams, place water-bath to be heated to 50 ℃, stir and make dissolving, get water;
(3) preparation Emulsion: oil phase and water are mixed down for 50 ℃, with emulsification pretreatment device emulsifying 20 minutes (5500 rev/mins of rotating speeds), get colostrum, regulating its pH with sodium hydroxide and hydrochloric acid solution is 4.58; With colostrum with the further emulsifying of high pressure homogenizer (pressure 13500psi), water for injection is quantitatively to 1000 milliliters, through the filtering with microporous membrane of 0.45 μ m, with filtrate fill nitrogen, gland after by every bottle of 100 milliliters of packing, with 115 ℃ of sterilizations of rotating type high-pressure steam sterilization still 45 minutes, Emulsion.After measured, the mean diameter of this Emulsion microgranule is 287nm, and pH is 4.0.
Assembly packaging is with embodiment 1.
Embodiment 8 preparation curcumin intravenous injections
1. the preparation of curcumin injection solution:
Get curcumin 3.75 grams, join in 90 milliliters the mixed with propylene glycol solvent, 72 ℃ of following stirring and dissolving are settled to 100 milliliters with propylene glycol then, and regulating pH jointly with an amount of malic acid and triethanolamine is 4, the needle-use activated carbon that adds 0.30 gram, 60 ℃ adsorbed 20 minutes down, used the filtering with microporous membrane of 0.45 μ m then, and filtrate is pressed every bottle of 4 milliliters of packing, gland, with 100 ℃ of sterilizations of flowing steam 60 minutes, promptly get the curcumin injection solution then.
2. the preparation of Emulsion:
(1) preparation oil phase: with Ganoderma spore oil 25 gram, Semen Maydis oil 25 grams, sad monoglyceride 90 grams, Sunfat GDC-S 30 grams, Semen Lini oil 30 grams, mix, place water-bath to be heated to 72 ℃, stirring and evenly mixing, oil phase;
(2) preparation water: get 400 milliliters of waters for injection, add soybean phospholipid 5 grams, glucose 50 grams place water-bath to be heated to 72 ℃, stir and make dissolving, get water;
(3) preparation Emulsion: oil phase and water are mixed down for 72 ℃,, get colostrum with emulsification pretreatment device emulsifying 20 minutes (7200 rev/mins of rotating speeds); With colostrum with the further emulsifying of high pressure homogenizer (pressure 5000psi), regulating its pH with sodium hydroxide solution is 8.63, water for injection is settled to 1000 milliliters, filter with incipient fusion formula funnel, filtrate is filled nitrogen, gland after by every bottle of 100 milliliters of packing, 115 ℃ of sterilizations of high steam 45 minutes get Emulsion.After measured, the mean diameter of this Emulsion microgranule is 500nm, and pH is 8.59.
Assembly packaging is with embodiment 1.
Embodiment 9 preparation curcumin intravenous injections
1. the preparation of curcumin injection solution:
Get curcumin 3 grams, join in the mixed solution of 95 milliliters of dimethyl acetylamide, 40 ℃ of following stirring and dissolving, be settled to 100 milliliters with dimethyl acetylamide then, add the needle-use activated carbon of 0.2 gram, 55 ℃ adsorbed 55 minutes down, use the filtering with microporous membrane of 0.45 μ m then, filtrate by every bottle of 5 milliliters of packing, gland, with 121 ℃ of sterilizations of high steam 25 minutes, is promptly got the curcumin injection solution then.
2. the preparation of Emulsion:
(1) preparation oil phase: with injection soybean oil 100 gram, decanoyl/octanoyl glycerides 100 grams, hot capric acid diglyceride 100 grams, egg yolk lecithin 5 gram mixings, place water-bath to be heated to 70 ℃, stir and make dissolving, oil phase;
(2) preparation water: get 600 milliliters of waters for injection, poloxamer 1 gram, glycerol 22.5 grams place water-bath to be heated to 70 ℃, stir and make dissolving, get water;
(3) prepare Emulsion: oil phase and water are mixed down for 70 ℃, with emulsification pretreatment device emulsifying 15 minutes (rotating speed 6500/ changes), get colostrum, regulating pH with sodium hydroxide and hydrochloric acid solution is 6.86; With colostrum with the further emulsifying of high pressure homogenizer (pressure 7000psi), water for injection is quantitatively to 1000 milliliters, through the filtering with microporous membrane of 0.45 μ m, filtrate filled nitrogen, gland after by every bottle of 100 milliliters of packing, with 121 ℃ of sterilizations of rotating type high-pressure steam sterilization still 35 minutes, get Emulsion.After measured, the mean diameter of this Emulsion microgranule is 320nm, and pH is 6.6.
Assembly packaging is with embodiment 1.
Embodiment 10 preparation curcumin intravenous injections
1. the preparation of curcumin injection solution:
Get curcumin 6 grams, join in the mixed solution of 90 milliliters of dimethyl acetylamide, 50 ℃ of following stirring and dissolving are settled to 100 milliliters with dimethyl acetylamide then, are 5.6 with an amount of Fructus Citri Limoniae acid for adjusting pH, the needle-use activated carbon that adds 0.5 gram, 60 ℃ adsorbed 50 minutes down, used the filtering with microporous membrane of 0.45 μ m then, and filtrate is pressed every bottle of 4 milliliters of packing, gland, use 121 ℃ of high pressure steam sterilizations 30 minutes then, promptly get the curcumin injection solution.
2. the preparation of Emulsion
(1) preparation oil phase: with hot tricaprin 35 grams of injection, Radix Oenotherae erythrosepalae oil 10 grams, Oleum Hippophae 10 grams, soybean oil 145 gram mixings, place water-bath to be heated to 50 ℃, add injection soybean phospholipid 25 grams, stirring and dissolving, oil phase;
(2) preparation water: get 650 milliliters of waters for injection, add sodium chloride 5 grams, place water-bath to be heated to 50 ℃, stir and make dissolving, get water;
(3) preparation Emulsion: oil phase and water are mixed down for 50 ℃,, get colostrum with emulsification pretreatment device emulsifying 25 minutes (1800 rev/mins of rotating speeds); With colostrum with the further emulsifying of high pressure homogenizer (pressure 20000psi), water for injection is settled to 1000 milliliters, regulating its pH with an amount of sodium hydroxide solution is 7.86, through 0.45 μ m filtering with microporous membrane, filtrate is filled nitrogen, gland after by every bottle of 250 milliliters of packing, with 105 ℃ of sterilizations of rotating type high-pressure steam sterilization still 45 minutes, get Emulsion.Through identifying that the mean diameter of this Emulsion microgranule is 186nm, pH is 7.5.
Assembly packaging is with embodiment 1.
Embodiment 11 preparation curcumin intravenous injections
1. the preparation of curcumin injection solution:
Get curcumin 8 grams, join in the mixed solvent of PEG400,20ml propylene glycol of 70ml, 85 ℃ of following stirring and dissolving, being settled to 100 milliliters with PEG400 then, is 3.5 with the Fructus Citri Limoniae acid for adjusting pH, and the needle-use activated carbon that adds 0.18 gram adsorbed 25 minutes down for 50 ℃, use the filtering with microporous membrane of 0.45 μ m then, filtrate by every bottle of 2 milliliters of packing, gland, with 110 ℃ of sterilizations of high steam 50 minutes, is promptly got the curcumin injection solution then.
2. the preparation of Emulsion:
(1) preparation oil phase: with Oleum Fructus Bruceae 14 gram, Semen Coicis oil 7 grams, tricaprin 5 grams, safflower oil 15 grams, fish oil 3 grams, Semen Maydis oil 16 grams, mix, place water-bath to be heated to 60 ℃, be stirred to dissolving, oil phase;
(2) preparation water: get 685 milliliters of waters for injection, add soybean phospholipid 12 gram, glycerol 22.5 gram mixings, place water-bath to be heated to 60 ℃ of dissolvings, water;
(3) preparation Emulsion: oil phase and water are mixed down for 60 ℃,, get colostrum with emulsification pretreatment device emulsifying 30 minutes (1800 rev/mins of rotating speeds); With colostrum with the further emulsifying of high pressure homogenizer (pressure 13000psi), water for injection is quantitatively to 1000 milliliters, regulating its pH with sodium hydroxide, sodium carbonate and sodium bicarbonate solution is 6.65, filter through sintered filter funnel, the filtering with microporous membrane of reuse 0.45 μ m, filtrate is filled nitrogen, gland after by every bottle of 100 milliliters of packing, 117 ℃ of sterilizations of rotating type high-pressure steam sterilization still 40 minutes, Emulsion.After measured, the mean diameter of this Emulsion microgranule is 198nm, and pH is 6.4.
The curcumin injection solution of 1 packing unit and the Emulsion assembly packaging of 2 packing units are in the same place.
Embodiment 12 preparation curcumin intravenous injections
1. the preparation of curcumin injection solution:
Get curcumin 0.5 gram, join in the mixed solvent of 65 milliliters PEG400 and 20 milliliters of propylene glycol, 30 ℃ of following stirring and dissolving are settled to 100 milliliters with PEG400 then, and regulating pH with malic acid and triethanolamine is 6.98, the needle-use activated carbon that adds 0.40 gram, adsorbed 60 minutes down at 25 ℃, use the filtering with microporous membrane of 0.45 μ m then, filtrate is pressed every bottle of 10 milliliters of packing, gland, with 100 ℃ of sterilizations of flowing steam 60 minutes, promptly get the curcumin injection solution then.
2. the preparation of Emulsion:
(1) preparation oil phase: with injection Oleum sesami 5 gram, Ganoderma spore oil 5 grams, oleic acid 1.2 grams, mix, place water-bath to be heated to 65 ℃, add egg yolk lecithin 12 grams, stir and make dissolving, oil phase;
(2) preparation water: get water for injection 840ml, add glycerol 22.5 grams, place water-bath to be heated to 65 ℃, get water;
(3) preparation Emulsion: oil phase and water are mixed down for 65 ℃, and stirring and emulsifying 60 minutes (800 rev/mins of rotating speeds) gets colostrum then; With colostrum with the further emulsifying of high pressure homogenizer (pressure 20000psi), water for injection is quantitatively to 1000 milliliters, regulating its pH with citric acid and sodium hydroxide solution is 7.69, filter with sintered filter funnel, filtrate is filled nitrogen, gland after by every bottle of 100 milliliters of packing, 115 ℃ of sterilizations of rotating type high-pressure steam sterilization still 50 minutes get Emulsion.After measured, the mean diameter of this Emulsion microgranule is 240nm, and pH is 7.40.
Assembly packaging is with embodiment 1.
Embodiment 13 preparation curcumin intravenous injections
1. the preparation of curcumin injection solution:
Get curcumin 3 grams, join in 90 milliliters the PEG400,55 ℃ of following stirring and dissolving are settled to 100 milliliters with PEG400 then, are 4.5 with the Fructus Citri Limoniae acid for adjusting pH, add 0.12 gram needle-use activated carbon, 65 ℃ adsorbed 45 minutes down, use the filtering with microporous membrane of 0.45 μ m then, again through 0.22 μ m filtering with microporous membrane degerming, by every bottle of 2 milliliters of aseptic subpackaged, glands, promptly get the curcumin injection solution.
2. the preparation of Emulsion:
(1) preparation oil phase: injection Herba Artemisiae Annuae oil 40 grams, capric acid monoglyceride 75 grams, capric acid diglyceride 75 grams, capric acid triglyceride 20 grams, Oleum Helianthi 50 grams are mixed, place water-bath to be heated to 80 ℃, add injection soybean phospholipid 12 grams, stir and make dissolving, get oil phase;
(2) preparation water: get 530 milliliters of waters for injection, add mannitol 60 grams, place water-bath to be heated to 75 ℃, get water;
(3) preparation Emulsion: oil phase and water are mixed down for 80 ℃,, get colostrum with emulsification pretreatment device emulsifying 20 minutes (2000 rev/mins of rotating speeds); Regulating pH with hydrochloric acid and sodium hydroxide solution is 8.50, with colostrum with the further emulsifying of high pressure homogenizer (pressure 15000psi), the injection water yield adds to 1000 milliliters, filter with sintered filter funnel, filtrate is filled nitrogen, gland after by every bottle of 250 milliliters of packing, 121 ℃ of sterilizations of high pressure 35 minutes get Emulsion.Through identifying that the mean diameter of this Emulsion microgranule is 234nm, pH is 8.30.
Assembly packaging is with embodiment 1.
Embodiment 14 preparation curcumin intravenous injections
1. the preparation of curcumin injection solution:
Get curcumin 5 grams, join in the mixed solution of the PEG400 of 75ml, 20 milliliters of dimethyl acetylamide, 65 ℃ of following stirring and dissolving are settled to 100 milliliters with PEG400 then, and regulating pH with lactic acid is 3.0, the needle-use activated carbon that adds 0.25 gram, 50 ℃ adsorbed 50 minutes down, used the filtering with microporous membrane of 0.22 μ m then, and filtrate is pressed every bottle of 2 milliliters of packing, gland, with 115 ℃ of sterilizations of high steam 40 minutes, promptly get the curcumin injection solution then.
2. the preparation of Emulsion:
(1) preparation oil phase: with hot capric acid diglyceride 10 grams of injection, sad monoglyceride 10 grams, Sunfat GDC-S 10 grams, Trivent OCG 10 grams, fish oil 10 grams, Oleum Helianthi 30 grams, Oleum Curcumae 20 gram mixings, place water-bath to be heated to 75 ℃, add injection soybean phospholipid 12 grams, oleic acid 0.1 gram, stirring makes dissolving, gets oil phase;
(2) preparation water: get 450 milliliters of waters for injection, add glycerol 24 gram mixings, place water-bath to be heated to 70 ℃, get water;
(3) preparation Emulsion: oil phase and water are mixed down for 75 ℃, with emulsification pretreatment device emulsifying 10 minutes (1300 rev/mins of rotating speeds), get colostrum, regulating its pH value with sodium hydroxide and sodium carbonate liquor is 6.4; With colostrum with the further emulsifying of high pressure homogenizer (pressure 10000psi), water for injection is quantitatively to 1000 milliliters, with the filtering with microporous membrane of 0.45 μ m, filtrate filled nitrogen, gland after by every bottle of 100 milliliters of packing, with 121 ℃ of sterilizations of rotating type high-pressure steam sterilization still 30 minutes, get Emulsion.After measured, the mean diameter of this Emulsion microgranule is 269nm, and pH is 5.88.
Assembly packaging is with embodiment 1.
Embodiment 15 preparation curcumin intravenous injections
1. the preparation of curcumin injection solution:
Get curcumin 3 grams, join in the mixed solution of dimethyl acetylamide of 60 milliliters PEG400 and 25 milliliters, 60 ℃ of following stirring and dissolving are settled to 100 milliliters with PEG400 then, and regulating pH with acetic acid is 4, the needle-use activated carbon that adds 0.48 gram, 30 ℃ adsorbed 60 minutes down, used the filtering with microporous membrane of 0.45 μ m then, and filtrate is pressed every bottle of 4 milliliters of packing, gland, with 115 ℃ of sterilizations of high steam 45 minutes, promptly get the curcumin injection solution then.
2. the preparation of Emulsion:
(1) prepares oil phase: place water-bath to be heated to 70 ℃ injection soybean oil 200 grams, add injection soybean phospholipid 12 grams, stir and make dissolving, get oil phase;
(2) preparation water: get 740 milliliters of waters for injection, glycerol 22.3g mixing, place water-bath to be heated to 70 ℃, get water;
(3) preparation Emulsion: oil phase and water are mixed down for 70 ℃, with emulsification pretreatment device emulsifying 15 minutes (1500 rev/mins of rotating speeds), get colostrum, regulating its pH with sodium hydroxide solution is 6.0; With colostrum with the further emulsifying of high pressure homogenizer (pressure 20000psi), water for injection is used the filtering with microporous membrane of 0.45 μ m then quantitatively to 1000 milliliters, and filtrate is filled nitrogen, gland after by every bottle of 100 milliliters of packing, with 121 ℃ of sterilizations of rotating type high-pressure steam sterilization still 30 minutes, get Emulsion.After measured, the mean diameter of this Emulsion microgranule is 220nm, and pH is 5.60.
Assembly packaging is with embodiment 1.
Embodiment 16 preparation curcumin intravenous injections
Get curcumin 5 grams, join in 90 milliliters of PEG400 solvents, 75 ℃ of following stirring and dissolving are settled to 100 milliliters with PEG400 then, are 4 with an amount of Fructus Citri Limoniae acid for adjusting pH, add 0.3 gram needle-use activated carbon, 70 ℃ adsorbed 25 minutes down, use the filtering with microporous membrane of 0.45 μ m then, with filtrate packing, gland, with 105 ℃ of sterilizations of high steam 45 minutes, promptly get the curcumin injection solution then.
Commercially available Emulsion: [specification]: 100 milliliters, in 20%/and long chain fat emulsion injection, [lot number]: GM1010005, [manufacturer]: Guangzhou Baite Jiaoguang Medical Product Co., Ltd
The curcumin injection solution can be packed separately, also can with commercially available Emulsion assembly packaging.During administration, curcumin injection solution and commercially available Emulsion by volume required than mixing, are got final product intravenous drip.Down together.
Embodiment 17 preparation curcumin intravenous injections
Get curcumin 4 grams, join in 92 milliliters the Liquid Macrogol, 80 ℃ of following stirring and dissolving are settled to 100 milliliters with Liquid Macrogol then, are 4 with the Fructus Citri Limoniae acid for adjusting pH, the needle-use activated carbon that adds 0.35 gram, 65 ℃ adsorbed 30 minutes down, use the filtering with microporous membrane of 0.45 μ m then, with filtrate packing, gland, with 115 ℃ of sterilizations of high steam 45 minutes, promptly get the curcumin injection solution then.
Commercially available Emulsion: [specification]: 250 milliliters, in 20%/and long chain fat emulsion injection, [lot number]: GM0906034, [manufacturer]: Guangzhou Baite Jiaoguang Medical Product Co., Ltd
Embodiment 18 preparation demethoxycurcumin intravenous injections
Remove methoxyl group curcumin 10 grams, join in the mixed solution of dehydrated alcohol of 80 milliliters PEG400 and 10 milliliters, add tocopherol 0.05 gram, 60 ℃ of following stirring and dissolving, be settled to 100 milliliters with PEG400 then, regulating pH with hydrochloric acid is 2.8, the needle-use activated carbon that adds 0.26 gram, 100 ℃ adsorbed 15 minutes down, use the filtering with microporous membrane of 0.45 μ m then, with filtrate packing, gland, with 105 ℃ of sterilizations of high steam 60 minutes, promptly get the demethoxycurcumin injection solution then.
Commercially available Emulsion: [specification]: 250 milliliters, in 20%/and long chain fat emulsion injection, [lot number]: 0104A182, [manufacturer]: the bright medical joint-stock company of German shellfish
Embodiment 19 preparation curcumin intravenous injections
Get curcumin 8 grams, join in the mixed solution of 55 milliliters propylene glycol, 20 milliliters dimethyl acetylamide and 5 milliliters of glycerol, 65 ℃ of following stirring and dissolving are settled to 100 milliliters with propylene glycol then, and regulating pH with lactic acid is 3.5, the needle-use activated carbon that adds 0.1 gram, 45 ℃ adsorbed 45 minutes down, use the filtering with microporous membrane of 0.45 μ m then, with filtrate packing, gland, with 121 ℃ of sterilizations of high steam 30 minutes, promptly get the curcumin injection solution then.
Commercially available Emulsion: with embodiment 17.
Embodiment 20 preparation curcumin intravenous injections
Get curcumin 7 grams, join in 85 milliliters the Macrogol 200, stirring under 70 ℃ and make dissolving, be settled to 100 milliliters with Macrogol 200 then, is 3.5 with the Fructus Citri Limoniae acid for adjusting pH, the needle-use activated carbon that adds 0.45 gram, 75 ℃ adsorbed 25 minutes down, use the filtering with microporous membrane of 0.45 μ m then, with filtrate packing, gland, with 115 ℃ of sterilizations of high steam 45 minutes, promptly get the curcumin injection solution then.
Commercially available Emulsion: [specification]: 100 milliliters, 20% fat emulsion injection, [lot number]: F090615A1, [manufacturer]: Kelun Pharm Ind Co., Ltd., Sichuan
Embodiment 21 preparation curcumin intravenous injections
Get curcumin 6 grams, join in the mixed liquor of PEG400 of 25 milliliters propylene glycol and 70 milliliters, 85 ℃ of following stirring and dissolving, be settled to 100 milliliters with PEG400 then, add the needle-use activated carbon of 0.5 gram, 35 ℃ adsorbed 45 minutes down, use the filtering with microporous membrane of 0.45 μ m then, with filtrate packing, gland, use 105 ℃ of high pressure steam sterilizations 60 minutes then, promptly get the curcumin injection solution.
Commercially available Emulsion: [specification]: 100 milliliters, 30% fat emulsion injection, [lot number]: 0812033, [manufacturer]: Xi'an ippon pharmaceutical Co. Ltd
Embodiment 22 preparation curcumin intravenous injections
Get curcumin 5 grams, join in 70 milliliters the Liquid Macrogol and 20 milliliters of Macrogol 200 mixed liquors, 70 ℃ of following stirring and dissolving are settled to 100 milliliters with Liquid Macrogol then, with the Fructus Mali pumilae acid for adjusting pH is 3.0, the needle-use activated carbon that adds 0.32 gram, 75 ℃ adsorbed 30 minutes down, use the filtering with microporous membrane of 0.45 μ m then, 0.22 μ m filtering with microporous membrane, with filtrate packing, gland, use 115 ℃ of high pressure steam sterilizations 30 minutes then, promptly get the curcumin injection solution.
Commercially available Emulsion: with embodiment 17.
Embodiment 23 preparation curcumin intravenous injections
Get curcumin 5 grams, join in 90 milliliters the Macrogol 200,72 ℃ of following stirring and dissolving are settled to 100 milliliters with Macrogol 200 then, and regulating pH jointly with an amount of malic acid and triethanolamine is 4, the needle-use activated carbon that adds 0.30 gram, 90 ℃ adsorbed 30 minutes down, use the filtering with microporous membrane of 0.45 μ m then, with filtrate packing, gland, with 100 ℃ of sterilizations of flowing steam 60 minutes, promptly get the curcumin injection solution then.
Commercially available Emulsion: with embodiment 16.
Embodiment 24 preparation bisdemethoxycurcumin intravenous injections
Get bisdemethoxycurcumin 3 grams, join in the mixed solvent of 85 milliliters of dimethyl acetylamide, 90 ℃ of following stirring and dissolving, be settled to 100 milliliters with dimethyl acetylamide then, add the needle-use activated carbon of 0.2 gram, 35 ℃ adsorbed 45 minutes down, use the filtering with microporous membrane of 0.45 μ m then, with filtrate packing, gland, with 121 ℃ of sterilizations of high steam 35 minutes, promptly get the bisdemethoxycurcumin injection solution then.
Commercially available Emulsion: with embodiment 17.
Embodiment 25 preparation curcumin intravenous injections
Get curcumin 2.5 grams, join in the mixed solution of 65 milliliters of PEG400s and 25 milliliters of dimethyl acetylamide, 50 ℃ of following stirring and dissolving are settled to 100 milliliters with PEG400 then, are 5.6 with an amount of Fructus Citri Limoniae acid for adjusting pH, the needle-use activated carbon that adds 0.5 gram, 30 ℃ adsorbed 50 minutes down, use the filtering with microporous membrane of 0.45 μ m then, with filtrate packing, gland, use 121 ℃ of high pressure steam sterilizations 30 minutes then, promptly get the curcumin injection solution.
Commercially available Emulsion: with embodiment 21.
Embodiment 26 preparation curcumin intravenous injections
Get in the mixed solvent that curcumin 4.5 gram joins the PEG400 of 60ml and 25 milliliters of propylene glycol, 85 ℃ of following stirring and dissolving, be settled to 100 milliliters with PEG400 then, with the Fructus Citri Limoniae acid for adjusting pH is 3.5, the needle-use activated carbon that adds 0.18 gram adsorbed 25 minutes down for 80 ℃, used the filtering with microporous membrane of 0.45 μ m then, with filtrate packing, gland, with 110 ℃ of sterilizations of high steam 50 minutes, promptly get the curcumin injection solution then.
Commercially available Emulsion: with embodiment 18.
Embodiment 27 preparation curcumin intravenous injections
Get curcumin 6 grams, join in the mixed solvent of 70 milliliters PEG400 and 25 milliliters of propylene glycol, 95 ℃ of following stirring and dissolving are settled to 100 milliliters with PEG400 then, are 4 with the Fructus Mali pumilae acid for adjusting pH, the needle-use activated carbon that adds 0.40 gram, adsorbed 60 minutes down at 25 ℃, use the filtering with microporous membrane of 0.45 μ m then, filtrate packing, gland, with 100 ℃ of sterilizations of flowing steam 60 minutes, promptly get the curcumin injection solution then.
Commercially available Emulsion: with embodiment 16.
Embodiment 28 preparation bisdemethoxycurcumin injection solutions
Get bisdemethoxycurcumin 5 grams, join in 95 milliliters the PEG400,55 ℃ of following stirring and dissolving are settled to 100 milliliters with PEG400 then, are 4.5 with the Fructus Citri Limoniae acid for adjusting pH, add 0.12 gram needle-use activated carbon, 65 ℃ adsorbed 30 minutes down, use the filtering with microporous membrane of 0.45 μ m then, again through 0.22 μ m filtering with microporous membrane degerming, aseptic subpackaged, promptly get the bisdemethoxycurcumin injection solution.
Embodiment 29 preparation demethoxycurcumin injection solutions
Remove methoxyl group curcumin 3 grams, join in the mixed solution of 75 milliliters of PEG400s and 15 milliliters of dimethyl acetylamide, 75 ℃ of following stirring and dissolving are settled to 100 milliliters with PEG400 then, are 4.5 with an amount of Fructus Citri Limoniae acid for adjusting pH, add 0.48 gram needle-use activated carbon, 70 ℃ adsorbed 25 minutes down, used the filtering with microporous membrane of 0.45 μ m then, will be with 105 ℃ of sterilizations of high steam 60 minutes after the filtrate packing, promptly get the demethoxycurcumin injection solution, store stand-by.
Embodiment 30 preparation curcumin injection solutions
Get curcumin 4 grams, join in the mixed solution of 65 milliliters of PEG400s and 25 milliliters of dimethyl acetylamide, 80 ℃ of following stirring and dissolving are settled to 100 milliliters with PEG400 then, and regulating pH with acetic acid is 4.5, the needle-use activated carbon that adds 0.35 gram, 65 ℃ adsorbed 30 minutes down, used the filtering with microporous membrane of 0.45 μ m then, will be with 115 ℃ of sterilizations of high steam 45 minutes after the filtrate packing, promptly get the curcumin injection solution, store stand-by.
The experiment of curcumin chemical compounds intravenous injection study on the stability:
1, use the prepared curcumin intravenous injection of embodiment 1, with curcumin injection solution and 1: 50 by volume mixing of Emulsion, the detection preparation is in medicament contg, Emulsion diameter of particle and the pH situation of change of different time.
The investigation method is: get 2 milliliters of curcumin injection solutions, be mixed into intravenous injection in the Emulsion with 100 milliliters of its addings; Measure medicament contg, particle diameter and the pH value of this intravenous injection with high performance liquid chromatography, particle size determination instrument, pH analyzer routinely respectively in different time points; To mix back 0 time point medicament contg is 100%, and other times point medicament contg is that injection filters back content and 0 time content percentage ratio relatively.When measuring medicament contg, each time point all will be measured the medicament contg that intravenous injection filters front and back, promptly before measure filtering behind the medicament contg of intravenous injection, with the filtering with microporous membrane of intravenous injection through 0.22 μ m, the drug crystallization of separating out with removal, measure the medicament contg in the filtrate again, each time point is replication 2 times at least, whether estimate medicine with the variation that records twice intravenous injection Chinese medicine content separates out, if the ratio of intravenous injection Chinese medicine content is lower than 98% before filter back and the filter, then surpass the systematic error scope and be considered as medicine and separate out, the testing result meansigma methods sees Table 1 and table 2.
Table 1. curcumin intravenous injection study on the stability result
Table 2. curcumin intravenous injection study on the stability result
2, be example with embodiment 16 prepared curcumin intravenous injections,, detect medicament contg, Emulsion microgranule mean diameter and the pH situation of change of preparation in different time points with curcumin injection solution and by volume 1: 50 mixing of Emulsion.
The investigation method is the same, the results are shown in Table 3 and table 4.
Table 3. curcumin intravenous injection study on the stability result
Table 4. curcumin intravenous injection study on the stability result
Find out that from table 1,2,3,4 curcumin intravenous injection filtrate Chinese medicine content in 18 hours does not almost change, illustrating does not have the curcumin crystallization to separate out; The Emulsion diameter of particle does not have significant change yet; PH value is kept constant basically, illustrates that the curcumin intravenous injection is good at 18 hours internal stabilities.Therefore, before the clinical use curcumin injection solution is mixed with Emulsion, its stability, drug loading satisfy the clinical application requirement fully.
The curcumin chemical compounds intravenous injection is to CCl
4The protection experiment of the acute liver damage that causes
1, laboratory animal and grouping: 60 of SPF level male SD rats, body weight 180～220 grams are raised in air-conditioned animal housing, and 20～25 ℃, relative humidity 60% uses the Mus special feed, freely drinks water.Animal is weighed, and numbering is divided into 4 groups at random by body weight, normal group, and model group, administration group (embodiment 1 prepared curcumin intravenous injection) and positive controls (Essentiale N/Essentiale Forte N, lot number: 2010051, Sanofi-Aventis company produces).(15 every group)
2, zoopery
Reference literature Li Haiyan etc. (Herba Diclipterae Chinensis polysaccharide hepatoprotective effect research [J]. Chinese crude drug, 2006,29 (8): 833-834) described, carry out zoopery, as follows:
Adopt the tail vein injection administration, be administered once every day, administration group dosage 10mg/kg (in the curcumin quality), positive controls Essentiale N/Essentiale Forte N dosage 60mg/kg (in polyene phosphatidylcholine), normal group gives isopyknic normal saline, in administration fasting in the 4th day 24 hours, administration group, positive controls and model group adopted 25% carbon tetrachloride peanut oil solution according to the 0.5ml/100g subcutaneous injection after last administration in the 5th day immediately, cause acute liver damage.18 hours ophthalmic corners of the eyes are got the about 1ml of blood after the modeling, and the centrifugal 10min of 3500r/min adopts full automatic biochemical apparatus to measure the content of serum alt, AST.
3, experimental result: because ALT, AST raise is the important symbol of hepatic injury, and ALT reacts the special degree of hepatic injury than AST height, and can medicine effectively reduce the ALT value is to judge whether medicine has the important symbol of anti-acute liver damage effect.
Table 5. curcumin chemical compounds intravenous injection is to the protective effect of acute liver damage
Experimental result (as table 5): model group rat blood serum ALT, AST content illustrate the modeling success apparently higher than normal group (P＜0.01).With model group relatively, curcumin intravenous injection administration group has ALT and the AST content in the obvious reduction Rats with Acute Liver Injury serum, and the reduction amount is higher than positive controls, illustrates that intravenous injection of the present invention has the effect of obvious treatment acute liver damage.
Claims (12)
1. curcumin chemical compounds injection solution, component and proportioning are as follows:
Said curcumin chemical compounds is selected from one or more in curcumin, demethoxycurcumin, the bisdemethoxycurcumin;
Said pH value regulator is selected from one or more in citric acid, malic acid, tartaric acid, acetic acid, lactic acid, phosphoric acid, triethanolamine, hydrochloric acid, sodium carbonate, sodium bicarbonate, the sodium hydroxide;
Said solvent for injection is selected from one or more in Macrogol 200, Liquid Macrogol, PEG400, propylene glycol, glycerol, dehydrated alcohol, the dimethyl acetylamide;
Said intercalating agent is a disodiumedetate; Said antioxidant is tocopherol.
2. by the described curcumin chemical compounds injection solution of claim 1, it is characterized in that said pH value regulator is a citric acid.
3. by claim 1 or 2 described curcumin chemical compounds injection solutions, it is characterized in that said solvent for injection is a PEG400.
4. by claim 1 or 2 described curcumin chemical compounds injection solutions, the content that it is characterized in that curcumin chemical compounds is 1%～6%.
5. by the described curcumin chemical compounds injection solution of claim 3, the content that it is characterized in that curcumin chemical compounds is 1%～6%.
6. by claim 1 or 2 or 5 described curcumin chemical compounds injection solutions, it is characterized in that pH value regulator adjusting pH to 3.0～4.5.
7. by the described curcumin chemical compounds injection solution of claim 3, it is characterized in that pH value regulator adjusting pH to 3.0～4.5.
8. by the described curcumin chemical compounds injection solution of claim 4, it is characterized in that pH value regulator adjusting pH to 3.0～4.5.
9. the preparation method of the described curcumin chemical compounds injection solution of claim 1, step is as follows:
Get curcumin chemical compounds to an amount of solvent for injection by proportioning, stir or shear dissolving down, add intercalating agent and antioxidant, be settled to capacity, regulate pH value with the pH regulator agent with solvent for injection by proportioning at 20～100 ℃; Add needle-use activated carbon then, the needle-use activated carbon addition is 0.02%～1% grams per milliliter, adsorbs 15～60 minutes after-filtration under 25～100 ℃ temperature, with the filtrate packing, seal, sterilizing gets final product.
10. curcumin chemical compounds intravenous injection, form by any described curcumin chemical compounds injection solution and Emulsion mixed preparing in the claim 1～8, with curcumin chemical compounds injection solution and Emulsion is 1: 5～250 mixings by volume, the curcumin chemical compounds intravenous injection, said Emulsion be in/long chain fat emulsion injection, fat emulsion injection or structural fatty emulsion injection.
11. by the described curcumin chemical compounds intravenous injection of claim 10, the volume ratio that it is characterized in that curcumin chemical compounds injection solution and Emulsion is 1: 10～100.
12. the assembly packaging of claim 10 or 11 described curcumin chemical compounds intravenous injections, it is characterized in that when assembly packaging, elder generation is packaged into curcumin chemical compounds injection solution and Emulsion respectively the packing unit of different capabilities, different according to curcumin chemical compounds injection solution and Emulsion mixed proportion again, with a packing unit of curcumin chemical compounds injection solution and a packing unit assembly packaging of Emulsion, perhaps a plurality of packing unit assembly packagings of the curcumin chemical compounds injection solution packing unit and Emulsion, perhaps a plurality of packing unit assembly packagings of a plurality of packing units of curcumin chemical compounds injection solution and Emulsion.
Priority Applications (2)
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| CN2011101063860A CN102225048A (en) | 2011-04-27 | 2011-04-27 | Curcumin compound injection and intravenous injection preparation thereof |
| PCT/CN2012/000546 WO2012146057A1 (en) | 2011-04-27 | 2012-04-23 | Curcuminoid injection solution and intravenous injection |
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| CN2011101063860A CN102225048A (en) | 2011-04-27 | 2011-04-27 | Curcumin compound injection and intravenous injection preparation thereof |
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Cited By (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102614121A (en) * | 2011-11-10 | 2012-08-01 | 上海天氏利医药科技有限公司 | Silibinin injection composition and preparation process |
| WO2012146057A1 (en) * | 2011-04-27 | 2012-11-01 | 中国人民解放军第二军医大学 | Curcuminoid injection solution and intravenous injection |
| CN104585730A (en) * | 2014-12-29 | 2015-05-06 | 上海染料研究所有限公司 | Preparation method of high-stability water soluble curcumin |
| CN105884597A (en) * | 2014-12-03 | 2016-08-24 | 石磊 | 2-alkoxy-4-((1E,6E)-7-(4-oxophenyl)-3,5-dioxo-1,6-heptadiene-1-yl)phenol metal salt derivative and application thereof |
| CN106667912A (en) * | 2017-02-08 | 2017-05-17 | 何德海 | Preparation method of curcumin nanometer emulsion |
| WO2020163899A1 (en) | 2019-02-11 | 2020-08-20 | Joseph Halstead | Therapeutically administrable high dose non-aqueous curcuminoid solutions |
| US11382871B2 (en) * | 2012-10-22 | 2022-07-12 | Briu Gmbh | Pharmaceutical composition containing curcumin |
| RU2808324C2 (en) * | 2019-02-11 | 2023-11-28 | Джозеф ХАЛСТЕД | Therapeutically applicable high-dose anhydrous solutions of curcuminoids |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1682701A (en) * | 2005-03-09 | 2005-10-19 | 山东大学 | Self microemulsifying preparation of curcumin and its preparing process |
| CN1891211A (en) * | 2006-05-16 | 2007-01-10 | 中国人民解放军第二军医大学 | Method for preparing curcumin lyophilized liposome |
| CN101708156A (en) * | 2009-12-10 | 2010-05-19 | 中国人民解放军第二军医大学 | Camptothecin medicament injection solution and injection and preparation method thereof |
| CN101708314A (en) * | 2009-12-10 | 2010-05-19 | 中国人民解放军第二军医大学 | Chinese medicinal essential oil injection solution, injection and preparation method thereof |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN100486567C (en) * | 2004-08-12 | 2009-05-13 | 山东绿叶天然药物研究开发有限公司 | Curcumin emulsion and its preparation process |
| CN102225048A (en) * | 2011-04-27 | 2011-10-26 | 中国人民解放军第二军医大学 | Curcumin compound injection and intravenous injection preparation thereof |
-
2011
- 2011-04-27 CN CN2011101063860A patent/CN102225048A/en active Pending
-
2012
- 2012-04-23 WO PCT/CN2012/000546 patent/WO2012146057A1/en active Application Filing
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1682701A (en) * | 2005-03-09 | 2005-10-19 | 山东大学 | Self microemulsifying preparation of curcumin and its preparing process |
| CN1891211A (en) * | 2006-05-16 | 2007-01-10 | 中国人民解放军第二军医大学 | Method for preparing curcumin lyophilized liposome |
| CN101708156A (en) * | 2009-12-10 | 2010-05-19 | 中国人民解放军第二军医大学 | Camptothecin medicament injection solution and injection and preparation method thereof |
| CN101708314A (en) * | 2009-12-10 | 2010-05-19 | 中国人民解放军第二军医大学 | Chinese medicinal essential oil injection solution, injection and preparation method thereof |
Non-Patent Citations (2)
| Title |
|---|
| 《中国药师》 20100430 杨文杰，等 姜黄素制剂的研究进展 565-567 第13卷, 第4期 * |
| 《中药材》 20020831 谭俊，等 姜黄素制剂稳定性实验研究 585-586 第25卷, 第8期 * |
Cited By (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2012146057A1 (en) * | 2011-04-27 | 2012-11-01 | 中国人民解放军第二军医大学 | Curcuminoid injection solution and intravenous injection |
| CN102614121A (en) * | 2011-11-10 | 2012-08-01 | 上海天氏利医药科技有限公司 | Silibinin injection composition and preparation process |
| CN102614121B (en) * | 2011-11-10 | 2013-12-11 | 上海天氏利医药科技有限公司 | Silibinin injection composition and preparation process |
| US11382871B2 (en) * | 2012-10-22 | 2022-07-12 | Briu Gmbh | Pharmaceutical composition containing curcumin |
| CN105884597A (en) * | 2014-12-03 | 2016-08-24 | 石磊 | 2-alkoxy-4-((1E,6E)-7-(4-oxophenyl)-3,5-dioxo-1,6-heptadiene-1-yl)phenol metal salt derivative and application thereof |
| CN104585730A (en) * | 2014-12-29 | 2015-05-06 | 上海染料研究所有限公司 | Preparation method of high-stability water soluble curcumin |
| CN106667912A (en) * | 2017-02-08 | 2017-05-17 | 何德海 | Preparation method of curcumin nanometer emulsion |
| WO2020163899A1 (en) | 2019-02-11 | 2020-08-20 | Joseph Halstead | Therapeutically administrable high dose non-aqueous curcuminoid solutions |
| CN113423393A (en) * | 2019-02-11 | 2021-09-21 | 约瑟夫·霍尔斯特德 | Therapeutically administrable high-dose non-aqueous curcumin solutions |
| EP3897598A4 (en) * | 2019-02-11 | 2022-09-14 | Joseph Halstead | Therapeutically administrable high dose non-aqueous curcuminoid solutions |
| RU2808324C2 (en) * | 2019-02-11 | 2023-11-28 | Джозеф ХАЛСТЕД | Therapeutically applicable high-dose anhydrous solutions of curcuminoids |
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| WO2012146057A1 (en) | 2012-11-01 |
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