CN103751785A - Silymarin-phospholipid complex and preparation method thereof - Google Patents
Silymarin-phospholipid complex and preparation method thereof Download PDFInfo
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- CN103751785A CN103751785A CN201410039334.XA CN201410039334A CN103751785A CN 103751785 A CN103751785 A CN 103751785A CN 201410039334 A CN201410039334 A CN 201410039334A CN 103751785 A CN103751785 A CN 103751785A
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Abstract
The invention relates to the technical field of pharmaceutical preparations, in particular to a silymarin-phospholipid complex and a preparation method thereof and a silybin-phospholipid complex soft capsule prepared from the complex. According to the silymarin-phospholipid complex and the preparation process, a phospholipid complex is prepared from silymarin, so that the water solubility of the silymarin is greatly improved, the lipid solubility and water solubility of the obtained complex are balanced, and the bioavailability is greatly improved; moreover, the silymarin-phospholipid complex soft capsules prepared from the complex also have high bioavailability, and are convenient to take; the utilization of the silymarin is greatly promoted.
Description
Technical field
The present invention relates to technical field of medicine, relate in particular to silymarin phosphatide complexes and preparation technology thereof, and the silymarin phosphatide complexes soft capsule preparing with this complex.
Background technology
Silymarin be from feverfew Herba Silybi mariani (pale reddish brown) (
silybum marianum(L.) in seed Gaertn), extract a kind of flavone compound obtaining.It is a kind of yellow or brown ceramic powder, and its main component is the materials such as silibinin, Isosilybin, silidianin and Silychristin.Herba Silybi mariani is good hepatoprotective plant, on the books in the classical works in Greece and Rome as far back as 1st century of Christian era.And the main effective ingredient of hepatoprotective is exactly silymarin in Herba Silybi mariani.Silymarin can be protected and stable liver plasma membrane, and antagonism hepatic necrosis, alleviates steatosis, suppresses increasing of glutamate pyruvate transaminase.Clinically be used for the treatment of acute hepatitis, chronic hepatitis, early stage liver cirrhosis and toxic hepatitis etc.Silymarin can also prevent the damage that ethanol, chemical toxicant, heavy metal, medicine, sitotoxin, environmental pollution etc. cause liver, promotes hepatocellular regeneration and reparation, so be called as " natural hepatoprotective ".In addition, silymarin, as powerful antioxidant, can be removed the free radical in human body, slow down aging, and there is radioprotective, prevent the effects such as arteriosclerosis.Therefore, silymarin is widely used in the fields such as medicine, health product, foods and cosmetics.
In Europe, utilize the existing thousands of years histories of Herba Silybi mariani treatment hepatopathy.China is as far back as the beginning of the fifties, introduces Herba Silybi mariani view and admire by Britain, among the peoplely with it, treats liver and gall diseases.Its medical efficacy begins one's study the beginning of the seventies.Chinese scholars has been carried out a large amount of research to the effective ingredient of Herba Silybi mariani, and develops product Yiganling tablet and Fufang Yiganling tablets, abroad the also grand Tablet and Capsula agent of favourable liver.
Silymarin is in the market fat-soluble good, poorly water-soluble, and oral administration biaavailability is low, therefore need to take certain technique to obtain water solublity and the fat-soluble silymarin of taking into account.Have been reported and find that some compound notice can obtain water solublity and the fat-soluble product of taking into account after being prepared into phosphatide complexes, thereby greatly improve the oral administration biaavailability of product.The present invention utilizes phospholipid complex technique prepare silymarin phosphatide complexes and prepare soft capsule as raw material exactly.
Summary of the invention
First technical problem to be solved by this invention is to provide a kind of silymarin phosphatide complexes, silymarin and phospholipid are prepared into complex, improved the water solublity of silymarin, acquisition has water solublity and fat-soluble silymarin phosphatide complexes concurrently, improves the oral administration biaavailability of silymarin.
The technical scheme that the present invention solves the problems of the technologies described above is:
In the middle of being dissolved in respectively to ethanol, silymarin and phospholipid forms solution ultrasonic at a certain temperature, then immediately two solution are mixed also again ultrasonic at a certain temperature, then by the mixed solution heating of ultrasonic mistake, ice bath cool overnight immediately after heating, then use this mixed solution of infrared lamp irradiation, reduction vaporization, removal ethanol, after treating the complete evaporate to dryness of solvent, then be drying to obtain silymarin phosphatide complexes dry product again.
Further, the preparation method of silymarin phosphatide complexes, step is as follows:
(1) silymarin is dissolved in and forms solution in the middle of the ethanol of 30 times of quality and under 400 W power, 50 ° of C ultrasonic 15 minutes; Phospholipid is dissolved in and forms solution in the middle of the ethanol of 10 times of quality and under 400 W power, 50 ° of C ultrasonic 15 minutes;
(2) by above-mentioned two solution, according to silymarin and the mass ratio of phospholipid, be that 1:5 mixes and under 400 W power, 50 ° of C ultrasonic 0.5 hour again immediately, then by the mixed solution of ultrasonic mistake at 70 ° of C heating 1h, ice bath cool overnight immediately after heating;
(3) with infrared lamp irradiation above-mentioned mixed solution 20 minutes, then reduction vaporization, remove ethanol, after treating the complete evaporate to dryness of solvent, more 45 ° of C forced air dryings obtain silymarin phosphatide complexes dry product.
Second technical problem to be solved by this invention is to provide a kind of soft capsule being comprised of silymarin phosphatide complexes, by silymarin phosphatide complexes is finally sealed and made soft capsule by certain step together with other substrate.Prepared soft capsule has the total attribute of soft capsule, if bioavailability is compared with feature high, that side effect is little, drug effect is high.
The technical scheme that the present invention solves the problems of the technologies described above is: soft capsule is become by silymarin phosphatide complexes and other matrix group, the shared percentage by weight of silymarin phosphatide complexes is 25%, and the percentage by weight of other described each component of substrate is: PEG400 is 40%, polyethylene glycol 6000 is 5%, glycerol is 30%.
Or soft capsule is become by silymarin phosphatide complexes and other matrix group, the shared percentage by weight of silymarin phosphatide complexes is 25%, and the percentage by weight of other described each component of substrate is: vegetable oil 70%, Cera Flava are 5%.Vegetable oil of the present invention is one or several of soybean oil, Oleum Cocois, Oleum Camelliae, vegetable oil.
Hepadestal soft capsule preparation method of the present invention is for to be mixed to form substrate by PEG400, polyethylene glycol 6000 and glycerol, and this substrate is ultrasonic; Silymarin phosphatide complexes as claimed in claim 5 is joined in the substrate after ultrasonic, and again ultrasonic, and the matrix solution that guarantees to be dissolved with silymarin phosphatide complexes by ice bath in ultrasonic middle temperature lower than 35 ° of C; Ultrasonic afterwards immediately with the above-mentioned matrix solution that is dissolved with silymarin phosphatide complexes of infrared lamp irradiation; Take gelatin as capsule skin, be pressed into soft capsule, packing, obtains finished product.
The preparation method of further a kind of Hepadestal soft capsule, is characterized in that step is as follows:
(1) PEG400 of 40 parts, the polyethylene glycol 6000 of 5 parts and the glycerol of 30 parts are mixed to form to substrate, and by this substrate under 400W power ultrasonic 15 minutes;
(2) the silymarin phosphatide complexes as claimed in claim 5 of 25 parts is joined in ultrasonic substrate afterwards, and under 400W power ultrasonic 30 minutes again, and the matrix solution that guarantees to be dissolved with silymarin phosphatide complexes by ice bath in ultrasonic middle temperature lower than 35 ° of C;
(1) after ultrasonic immediately with the above-mentioned matrix solution that is dissolved with silymarin phosphatide complexes of infrared lamp irradiation 2 minutes; Take gelatin as capsule skin, be pressed into soft capsule, packing, obtains finished product.
Or Hepadestal soft capsule preparation method of the present invention is for to be mixed to form substrate by vegetable oil and Cera Flava, and this substrate is ultrasonic; Silymarin phosphatide complexes as claimed in claim 5 is joined in the substrate after ultrasonic, and again ultrasonic, and the matrix solution that guarantees to be dissolved with silymarin phosphatide complexes by ice bath in ultrasonic middle temperature lower than 35 ° of C; Ultrasonic afterwards immediately with the above-mentioned matrix solution that is dissolved with silymarin phosphatide complexes of infrared lamp irradiation; Take gelatin as capsule skin, be pressed into soft capsule, packing, obtains finished product.
The preparation method of further a kind of Hepadestal soft capsule, is characterized in that step is as follows:
(1) vegetable oil of 70 parts, the Cera Flava of 5 parts are mixed to form to substrate, and by this substrate under 400W power ultrasonic 15 minutes;
(2) the silymarin phosphatide complexes as claimed in claim 5 of 25 parts is joined in ultrasonic substrate afterwards, and under 400W power ultrasonic 30 minutes again, and the matrix solution temperature that guarantees to be dissolved with silymarin phosphatide complexes by ice bath in ultrasonic lower than 35 ° of C;
(3) after ultrasonic immediately with the above-mentioned matrix solution that is dissolved with silymarin phosphatide complexes of infrared lamp irradiation 2 minutes; Take gelatin as capsule skin, be pressed into soft capsule, packing, obtains finished product.
Further described vegetable oil is one or several of soybean oil, Oleum Cocois, Oleum Camelliae, vegetable oil.
The present invention has following advantages: (1) the present invention becomes liposome by medicine with phospholipids incorporate, increases insoluble drug silymarin fat-soluble, and medicine is easily absorbed, and increases the bioavailability after drug oral, and rapidly, toxic and side effects is little in drug effect performance.(2) the present invention uses fat-soluble substrate and medicine intermiscibility are good, have increased the stability of medicine; (3) good, the safety of product hermeticity, dosage is accurate, dosage form is stable, aesthetic in appearance, carry with easy to use.
The specific embodiment
For the ease of it will be appreciated by those skilled in the art that the present invention will be further described below in conjunction with embodiment.
the preparation of embodiment 1 Herba Silybi mariani extract
The Herba Silybi mariani seed of the full seed through screening, oils and fats in the middle of first removing by the method for mechanical expression obtains the cake of Herba Silybi mariani seed, get 500 grams of cakes and add 2000ml acetone, after soaking after 2 hours, being heated to 60 degrees Celsius extracts 16 hours, at 60 degrees Celsius, concentrate 6 hours, afterwards 85 degrees Celsius of dry 48.7 grams of Herba Silybi mariani extract that obtain for 1 hour.
the preparation of embodiment 2 silymarin
48.7 grams of Herba Silybi mariani extract that embodiment 1 is prepared join 600 RPM in the n-hexane of 200 grams and stir 0.5 hour, then after standing 30 minutes, sucking filtration is removed n-hexane solution (in solution containing lipophilic substances such as oils and fatss); In triplicate, obtain the Herba Silybi mariani extract deoiling; Again the Herba Silybi mariani extract after deoiling is joined and in the alcoholic solution of 50% mass concentration of 200 grams, stir sucking filtration after 0.5 hour and obtain clear filtrate, by clear filtrate 75 degrees Celsius of lower vacuum concentration 2.5 hours, then concentrated paste is laid in rustless steel drip pan, 80 degrees Celsius of vacuum dryings 3 hours, pulverize and obtain 29.2 grams, the dry powder of silymarin.
the preparation of embodiment 3 silymarin phosphatide complexes
The silymarin that 10 grams of embodiment 2 are prepared is dissolved in and forms solution in the middle of 300 grams of ethanol and under 400 W power, 50 ° of C ultrasonic 15 minutes.50 grams of soybean lecithins are dissolved in and form solution in the middle of 500 grams of ethanol and under 400 W power, 50 ° of C ultrasonic 15 minutes.
Immediately above-mentioned two solution are mixed and under 400 W power, 50 ° of C ultrasonic 0.5 hour again, then by the mixed solution of ultrasonic mistake at 70 ° of C heating 1h, ice bath cool overnight immediately after heating.With the above-mentioned mixed solution of infrared lamp irradiation 20 minutes, then reduction vaporization, remove ethanol, after treating the complete evaporate to dryness of solvent, more 45 ° of C forced air dryings obtain 53.1 grams of silymarin phosphatide complexes dry products.
the preparation of embodiment 4 silymarin phosphatide complexes
The silymarin that 10 grams of embodiment 2 are prepared is dissolved in and forms solution in the middle of 300 grams of ethanol and under 400 W power, 50 ° of C ultrasonic 15 minutes.50 grams of phosphatidylcholines are dissolved in and form solution in the middle of 500 grams of ethanol and under 400 W power, 50 ° of C ultrasonic 15 minutes.
Immediately above-mentioned two solution are mixed and under 400 W power, 50 ° of C ultrasonic 0.5 hour again, then by the mixed solution of ultrasonic mistake at 70 ° of C heating 1h, ice bath cool overnight immediately after heating.With the above-mentioned mixed solution of infrared lamp irradiation 20 minutes, then reduction vaporization, remove ethanol, after treating the complete evaporate to dryness of solvent, more 45 ° of C forced air dryings obtain 51.7 grams of silymarin phosphatide complexes dry products.
the preparation of embodiment 5 silymarin phosphatide complexes
The silymarin that 10 grams of embodiment 2 are prepared is dissolved in and forms solution in the middle of 300 grams of ethanol and under 400 W power, 50 ° of C ultrasonic 15 minutes.50 grams of PHOSPHATIDYL ETHANOLAMINE are dissolved in and form solution in the middle of 500 grams of ethanol and under 400 W power, 50 ° of C ultrasonic 15 minutes.
Immediately above-mentioned two solution are mixed and under 400 W power, 50 ° of C ultrasonic 0.5 hour again, then by the mixed solution of ultrasonic mistake at 70 ° of C heating 1h, ice bath cool overnight immediately after heating.With the above-mentioned mixed solution of infrared lamp irradiation 20 minutes, then reduction vaporization, remove ethanol, after treating the complete evaporate to dryness of solvent, more 45 ° of C forced air dryings obtain 54.3 grams of silymarin phosphatide complexes dry products.
the preparation of embodiment 6 silymarin phosphatide complexes
The silymarin that 10 grams of embodiment 2 are prepared is dissolved in and forms solution in the middle of 300 grams of ethanol and under 400 W power, 50 ° of C ultrasonic 15 minutes.50 grams of Phosphatidylserine are dissolved in and form solution in the middle of 500 grams of ethanol and under 400 W power, 50 ° of C ultrasonic 15 minutes.
Immediately above-mentioned two solution are mixed and under 400 W power, 50 ° of C ultrasonic 0.5 hour again, then by the mixed solution of ultrasonic mistake at 70 ° of C heating 1h, ice bath cool overnight immediately after heating.With the above-mentioned mixed solution of infrared lamp irradiation 20 minutes, then reduction vaporization, remove ethanol, after treating the complete evaporate to dryness of solvent, more 45 ° of C forced air dryings obtain 52.9 grams of silymarin phosphatide complexes dry products.
the preparation of embodiment 7 silymarin phosphatide complexes
The silymarin that 10 grams of embodiment 2 are prepared is dissolved in and forms solution in the middle of 300 grams of ethanol and under 400 W power, 50 ° of C ultrasonic 15 minutes.20 grams of Phosphatidylserine and 30 grams of phosphatidylcholines are dissolved in and form solution in the middle of 500 grams of ethanol and under 400 W power, 50 ° of C ultrasonic 15 minutes.
Immediately above-mentioned two solution are mixed and under 400 W power, 50 ° of C ultrasonic 0.5 hour again, then by the mixed solution of ultrasonic mistake at 70 ° of C heating 1h, ice bath cool overnight immediately after heating.With the above-mentioned mixed solution of infrared lamp irradiation 20 minutes, then reduction vaporization, remove ethanol, after treating the complete evaporate to dryness of solvent, more 45 ° of C forced air dryings obtain 52.9 grams of silymarin phosphatide complexes dry products.
the preparation of embodiment 8 silymarin phosphatide complexes
The silymarin that 10 grams of embodiment 2 are prepared is dissolved in and forms solution in the middle of 300 grams of ethanol and under 400 W power, 50 ° of C ultrasonic 15 minutes.20 grams of Phosphatidylserine, 10 grams of phosphatidylcholines and 20 grams of Ovum Gallus domesticus Flavus lecithins are dissolved in and form solution in the middle of 500 grams of ethanol and under 400 W power, 50 ° of C ultrasonic 15 minutes.
Immediately above-mentioned two solution are mixed and under 400 W power, 50 ° of C ultrasonic 0.5 hour again, then by the mixed solution of ultrasonic mistake at 70 ° of C heating 1h, ice bath cool overnight immediately after heating.With the above-mentioned mixed solution of infrared lamp irradiation 20 minutes, then reduction vaporization, remove ethanol, after treating the complete evaporate to dryness of solvent, more 45 ° of C forced air dryings obtain 52.9 grams of silymarin phosphatide complexes dry products.
the preparation of embodiment 9 silymarin phosphatide complexes
The silymarin that 10 grams of embodiment 2 are prepared is dissolved in and forms solution in the middle of 300 grams of ethanol and under 400 W power, 50 ° of C ultrasonic 15 minutes.10 grams of Phosphatidylserine, 10 grams of phosphatidylcholines, 10 grams of soybean lecithins, 10 grams of Ovum Gallus domesticus Flavus lecithins and 10 grams of PHOSPHATIDYL ETHANOLAMINE are dissolved in and form solution in the middle of 500 grams of ethanol and under 400 W power, 50 ° of C ultrasonic 15 minutes.
Immediately above-mentioned two solution are mixed and under 400 W power, 50 ° of C ultrasonic 0.5 hour again, then by the mixed solution of ultrasonic mistake at 70 ° of C heating 1h, ice bath cool overnight immediately after heating.With the above-mentioned mixed solution of infrared lamp irradiation 20 minutes, then reduction vaporization, remove ethanol, after treating the complete evaporate to dryness of solvent, more 45 ° of C forced air dryings obtain 52.9 grams of silymarin phosphatide complexes dry products.
the preparation of embodiment 10 Hepadestal soft capsules
The PEG400 of 40 grams, the polyethylene glycol 6000 of 5 grams and the glycerol of 30 grams are mixed to form to substrate, and by this substrate under 400W power ultrasonic 15 minutes.By the embodiment of 25 grams
3 preparethe phosphatide complexes of silymarin join in the substrate after ultrasonic, and under 400W power ultrasonic 30 minutes again, and the matrix solution temperature of phosphatide complexes that guarantees to be dissolved with silymarin by ice bath in ultrasonic lower than 35 ° of C.After ultrasonic immediately with the above-mentioned matrix solution that is dissolved with silymarin phosphatide complexes of infrared lamp irradiation 2 minutes; Take gelatin as capsule skin, be pressed into 200 of soft capsules, packing, obtains finished product.
the preparation of embodiment 11 Hepadestal soft capsules
The PEG400 of 40 grams, the polyethylene glycol 6000 of 5 grams and the glycerol of 30 grams are mixed to form to substrate, and by this substrate under 400W power ultrasonic 15 minutes.By the embodiment of 25 grams
4 preparethe phosphatide complexes of silymarin join in the substrate after ultrasonic, and under 400W power ultrasonic 30 minutes again, and the matrix solution temperature of phosphatide complexes that guarantees to be dissolved with silymarin by ice bath in ultrasonic lower than 35 ° of C.After ultrasonic immediately with the above-mentioned matrix solution that is dissolved with silymarin phosphatide complexes of infrared lamp irradiation 2 minutes; Take gelatin as capsule skin, be pressed into 200 of soft capsules, packing, obtains finished product.
the preparation of embodiment 12 Hepadestal soft capsules
The PEG400 of 40 grams, the polyethylene glycol 6000 of 5 grams and the glycerol of 30 grams are mixed to form to substrate, and by this substrate under 400W power ultrasonic 15 minutes.By the embodiment of 25 grams
5 preparethe phosphatide complexes of silymarin join in the substrate after ultrasonic, and under 400W power ultrasonic 30 minutes again, and the matrix solution temperature of phosphatide complexes that guarantees to be dissolved with silymarin by ice bath in ultrasonic lower than 35 ° of C.After ultrasonic immediately with the above-mentioned matrix solution that is dissolved with silymarin phosphatide complexes of infrared lamp irradiation 2 minutes; Take gelatin as capsule skin, be pressed into 200 of soft capsules, packing, obtains finished product.
the preparation of embodiment 13 Hepadestal soft capsules
The PEG400 of 40 grams, the polyethylene glycol 6000 of 5 grams and the glycerol of 30 grams are mixed to form to substrate, and by this substrate under 400W power ultrasonic 15 minutes.By the embodiment of 25 grams
6 preparethe phosphatide complexes of silymarin join in the substrate after ultrasonic, and under 400W power ultrasonic 30 minutes again, and the matrix solution temperature of phosphatide complexes that guarantees to be dissolved with silymarin by ice bath in ultrasonic lower than 35 ° of C.After ultrasonic immediately with the above-mentioned matrix solution that is dissolved with silymarin phosphatide complexes of infrared lamp irradiation 2 minutes; Take gelatin as capsule skin, be pressed into 200 of soft capsules, packing, obtains finished product.
the preparation of embodiment 14 Hepadestal soft capsules
The PEG400 of 40 grams, the polyethylene glycol 6000 of 5 grams and the glycerol of 30 grams are mixed to form to substrate, and by this substrate under 400W power ultrasonic 15 minutes.By the embodiment of 25 grams
7 preparethe phosphatide complexes of silymarin join in the substrate after ultrasonic, and under 400W power ultrasonic 30 minutes again, and the matrix solution temperature of phosphatide complexes that guarantees to be dissolved with silymarin by ice bath in ultrasonic lower than 35 ° of C.After ultrasonic immediately with the above-mentioned matrix solution that is dissolved with silymarin phosphatide complexes of infrared lamp irradiation 2 minutes; Take gelatin as capsule skin, be pressed into 200 of soft capsules, packing, obtains finished product.
the preparation of embodiment 15 Hepadestal soft capsules
The PEG400 of 40 grams, the polyethylene glycol 6000 of 5 grams and the glycerol of 30 grams are mixed to form to substrate, and by this substrate under 400W power ultrasonic 15 minutes.By the embodiment of 25 grams
8 preparethe phosphatide complexes of silymarin join in the substrate after ultrasonic, and under 400W power ultrasonic 30 minutes again, and the matrix solution temperature of phosphatide complexes that guarantees to be dissolved with silymarin by ice bath in ultrasonic lower than 35 ° of C.After ultrasonic immediately with the above-mentioned matrix solution that is dissolved with silymarin phosphatide complexes of infrared lamp irradiation 2 minutes; Take gelatin as capsule skin, be pressed into 200 of soft capsules, packing, obtains finished product.
the preparation of embodiment 16 Hepadestal soft capsules
The PEG400 of 40 grams, the polyethylene glycol 6000 of 5 grams and the glycerol of 30 grams are mixed to form to substrate, and by this substrate under 400W power ultrasonic 15 minutes.By the embodiment of 25 grams
9 preparethe phosphatide complexes of silymarin join in the substrate after ultrasonic, and under 400W power ultrasonic 30 minutes again, and the matrix solution temperature of phosphatide complexes that guarantees to be dissolved with silymarin by ice bath in ultrasonic lower than 35 ° of C.After ultrasonic immediately with the above-mentioned matrix solution that is dissolved with silymarin phosphatide complexes of infrared lamp irradiation 2 minutes; Take gelatin as capsule skin, be pressed into 200 of soft capsules, packing, obtains finished product.
the preparation of embodiment 17 Hepadestal soft capsules
The Cera Flava of the soybean oil of 70 grams and 5 grams is mixed to form to substrate, and by this substrate under 400W power ultrasonic 15 minutes.By the embodiment of 25 grams
3 preparethe phosphatide complexes of silymarin join in the substrate after ultrasonic, and under 400W power ultrasonic 30 minutes again, and the matrix solution temperature of phosphatide complexes that guarantees to be dissolved with silymarin by ice bath in ultrasonic lower than 35 ° of C.After ultrasonic immediately with the above-mentioned matrix solution that is dissolved with silymarin phosphatide complexes of infrared lamp irradiation 2 minutes; Take gelatin as capsule skin, be pressed into 200 of soft capsules, packing, obtains finished product.
the preparation of embodiment 18 Hepadestal soft capsules
The Cera Flava of the Oleum Camelliae of 70 grams and 5 grams is mixed to form to substrate, and by this substrate under 400W power ultrasonic 15 minutes.By the embodiment of 25 grams
4 preparethe phosphatide complexes of silymarin join in the substrate after ultrasonic, and under 400W power ultrasonic 30 minutes again, and the matrix solution temperature of phosphatide complexes that guarantees to be dissolved with silymarin by ice bath in ultrasonic lower than 35 ° of C.After ultrasonic immediately with the above-mentioned matrix solution that is dissolved with silymarin phosphatide complexes of infrared lamp irradiation 2 minutes; Take gelatin as capsule skin, be pressed into 200 of soft capsules, packing, obtains finished product.
the preparation of embodiment 19 Hepadestal soft capsules
The Cera Flava of the vegetable oil of 70 grams and 5 grams is mixed to form to substrate, and by this substrate under 400W power ultrasonic 15 minutes.By the embodiment of 25 grams
5 preparethe phosphatide complexes of silymarin join in the substrate after ultrasonic, and under 400W power ultrasonic 30 minutes again, and the matrix solution temperature of phosphatide complexes that guarantees to be dissolved with silymarin by ice bath in ultrasonic lower than 35 ° of C.After ultrasonic immediately with the above-mentioned matrix solution that is dissolved with silymarin phosphatide complexes of infrared lamp irradiation 2 minutes; Take gelatin as capsule skin, be pressed into 200 of soft capsules, packing, obtains finished product.
the preparation of embodiment 20 Hepadestal soft capsules
The Cera Flava of the Oleum Cocois of 70 grams and 5 grams is mixed to form to substrate, and by this substrate under 400W power ultrasonic 15 minutes.By the embodiment of 25 grams
6 preparethe phosphatide complexes of silymarin join in the substrate after ultrasonic, and under 400W power ultrasonic 30 minutes again, and the matrix solution temperature of phosphatide complexes that guarantees to be dissolved with silymarin by ice bath in ultrasonic lower than 35 ° of C.After ultrasonic immediately with the above-mentioned matrix solution that is dissolved with silymarin phosphatide complexes of infrared lamp irradiation 2 minutes; Take gelatin as capsule skin, be pressed into 200 of soft capsules, packing, obtains finished product.
the preparation of embodiment 21 Hepadestal soft capsules
The vegetable oil of 35 grams, the soybean oil of 35 grams and the Cera Flava of 5 grams are mixed to form to substrate, and by this substrate under 400W power ultrasonic 15 minutes.By the embodiment of 25 grams
7 preparethe phosphatide complexes of silymarin join in the substrate after ultrasonic, and under 400W power ultrasonic 30 minutes again, and the matrix solution temperature of phosphatide complexes that guarantees to be dissolved with silymarin by ice bath in ultrasonic lower than 35 ° of C.After ultrasonic immediately with the above-mentioned matrix solution that is dissolved with silymarin phosphatide complexes of infrared lamp irradiation 2 minutes; Take gelatin as capsule skin, be pressed into 200 of soft capsules, packing, obtains finished product.
the preparation of embodiment 22 Hepadestal soft capsules
The Oleum Cocois of 35 grams, the Oleum Camelliae of 35 grams and the Cera Flava of 5 grams are mixed to form to substrate, and by this substrate under 400W power ultrasonic 15 minutes.The phosphatide complexes of the silymarin that the embodiment of 25 grams 8 is prepared joins in ultrasonic substrate afterwards, and under 400W power ultrasonic 30 minutes again, and the matrix solution temperature of phosphatide complexes that guarantees to be dissolved with silymarin by ice bath in ultrasonic lower than 35 ° of C.After ultrasonic immediately with the above-mentioned matrix solution that is dissolved with silymarin phosphatide complexes of infrared lamp irradiation 2 minutes; Take gelatin as capsule skin, be pressed into 200 of soft capsules, packing, obtains finished product.
the preparation of embodiment 23 Hepadestal soft capsules
The soybean oil of 30 grams, the Oleum Cocois of 20 grams, the Oleum Camelliae of 20 grams and the Cera Flava of 5 grams are mixed to form to substrate, and by this substrate under 400W power ultrasonic 15 minutes.The phosphatide complexes of the silymarin that the embodiment of 25 grams 9 is prepared joins in ultrasonic substrate afterwards, and under 400W power ultrasonic 30 minutes again, and the matrix solution temperature of phosphatide complexes that guarantees to be dissolved with silymarin by ice bath in ultrasonic lower than 35 ° of C.After ultrasonic immediately with the above-mentioned matrix solution that is dissolved with silymarin phosphatide complexes of infrared lamp irradiation 2 minutes; Take gelatin as capsule skin, be pressed into 200 of soft capsules, packing, obtains finished product.
the preparation of embodiment 24 Hepadestal soft capsules
The soybean oil of 30 grams, the vegetable oil of 20 grams, the Oleum Camelliae of 20 grams and the Cera Flava of 5 grams are mixed to form to substrate, and by this substrate under 400W power ultrasonic 15 minutes.The phosphatide complexes of the silymarin that the embodiment of 25 grams 4 is prepared joins in ultrasonic substrate afterwards, and under 400W power ultrasonic 30 minutes again, and the matrix solution temperature of phosphatide complexes that guarantees to be dissolved with silymarin by ice bath in ultrasonic lower than 35 ° of C.After ultrasonic immediately with the above-mentioned matrix solution that is dissolved with silymarin phosphatide complexes of infrared lamp irradiation 2 minutes; Take gelatin as capsule skin, be pressed into 200 of soft capsules, packing, obtains finished product.
the preparation of embodiment 25 Hepadestal soft capsules
The soybean oil of 20 grams, the vegetable oil of 20 grams, the Oleum Camelliae of 20 grams, the Oleum Cocois of 10 grams and the Cera Flava of 5 grams are mixed to form to substrate, and by this substrate under 400W power ultrasonic 15 minutes.The phosphatide complexes of the silymarin that the embodiment of 25 grams 6 is prepared joins in ultrasonic substrate afterwards, and under 400W power ultrasonic 30 minutes again, and the matrix solution temperature of phosphatide complexes that guarantees to be dissolved with silymarin by ice bath in ultrasonic lower than 35 ° of C.After ultrasonic immediately with the above-mentioned matrix solution that is dissolved with silymarin phosphatide complexes of infrared lamp irradiation 2 minutes; Take gelatin as capsule skin, be pressed into 200 of soft capsules, packing, obtains finished product.
the preparation of embodiment 26 Hepadestal soft capsules
The soybean oil of 20 grams, the vegetable oil of 20 grams, the Oleum Camelliae of 20 grams, the Oleum Cocois of 10 grams and the Cera Flava of 5 grams are mixed to form to substrate, and by this substrate under 400W power ultrasonic 15 minutes.The phosphatide complexes of the silymarin that the embodiment of 25 grams 8 is prepared joins in ultrasonic substrate afterwards, and under 400W power ultrasonic 30 minutes again, and the matrix solution temperature of phosphatide complexes that guarantees to be dissolved with silymarin by ice bath in ultrasonic lower than 35 ° of C.After ultrasonic immediately with the above-mentioned matrix solution that is dissolved with silymarin phosphatide complexes of infrared lamp irradiation 2 minutes; Take gelatin as capsule skin, be pressed into 200 of soft capsules, packing, obtains finished product.
Claims (12)
1. the preparation method of silymarin phosphatide complexes, it is characterized in that: in the middle of silymarin and phospholipid are dissolved in respectively to ethanol, form solution ultrasonic at a certain temperature, then immediately two solution are mixed also again ultrasonic at a certain temperature, then by the mixed solution heating of ultrasonic mistake, ice bath cool overnight immediately after heating, then uses this mixed solution of infrared lamp irradiation, then reduction vaporization, removes ethanol, after treating the complete evaporate to dryness of solvent, then be drying to obtain silymarin phosphatide complexes dry product.
2. the preparation method of silymarin phosphatide complexes as claimed in claim 1, is characterized in that step is as follows:
Silymarin is dissolved in and forms solution in the middle of the ethanol of 30 times of quality and under 400 W power, 50 ° of C ultrasonic 15 minutes; Phospholipid is dissolved in and forms solution in the middle of the ethanol of 10 times of quality and under 400 W power, 50 ° of C ultrasonic 15 minutes;
By above-mentioned two solution, according to silymarin and the mass ratio of phospholipid, be that 1:5 mixes and under 400 W power, 50 ° of C ultrasonic 0.5 hour again immediately, then by the mixed solution of ultrasonic mistake at 70 ° of C heating 1h, ice bath cool overnight immediately after heating;
With the above-mentioned mixed solution of infrared lamp irradiation 20 minutes, then reduction vaporization, remove ethanol, after treating the complete evaporate to dryness of solvent, more 45 ° of C forced air dryings obtain silymarin phosphatide complexes dry product.
3. the preparation method of silymarin phosphatide complexes as claimed in claim 2, is characterized in that: described phospholipid is selected from the middle of lecithin, phosphatidylcholine, PHOSPHATIDYL ETHANOLAMINE or Phosphatidylserine a kind or multiple.
4. the preparation method of silymarin phosphatide complexes as claimed in claim 3, is characterized in that: wherein said lecithin is selected from a kind or 2 kinds in the middle of soybean lecithin or Ovum Gallus domesticus Flavus lecithin.
5. silymarin phosphatide complexes, the preparation method it is characterized by by the silymarin phosphatide complexes described in claim 1-4 any one prepares.
6. a Hepadestal soft capsule, it is characterized in that, by silymarin phosphatide complexes as claimed in claim 5 and other matrix group, become, the shared percentage by weight of silymarin phosphatide complexes is 25%, and the percentage by weight of other described each component of substrate is: PEG400 is 40%, polyethylene glycol 6000 is 5%, glycerol is 30%.
7. a Hepadestal soft capsule, it is characterized in that, by silymarin phosphatide complexes claimed in claim 5 and other matrix group, become, the shared percentage by weight of silymarin phosphatide complexes is 25%, and the percentage by weight of other described each component of substrate is: vegetable oil 70%, Cera Flava are 5%.
8. a preparation method for Hepadestal soft capsule, is characterized in that, PEG400, polyethylene glycol 6000 and glycerol are mixed to form to substrate, and this substrate is ultrasonic; Silymarin phosphatide complexes as claimed in claim 5 is joined in the substrate after ultrasonic, and again ultrasonic, and the matrix solution that guarantees to be dissolved with silymarin phosphatide complexes by ice bath in ultrasonic middle temperature lower than 35 ° of C; Ultrasonic afterwards immediately with the above-mentioned matrix solution that is dissolved with silymarin phosphatide complexes of infrared lamp irradiation; Take gelatin as capsule skin, be pressed into soft capsule, packing, obtains finished product.
9. the preparation method of a kind of Hepadestal soft capsule as claimed in claim 8, is characterized in that step is as follows:
The PEG400 of 40 parts, the polyethylene glycol 6000 of 5 parts and the glycerol of 30 parts are mixed to form to substrate, and by this substrate under 400W power ultrasonic 15 minutes;
The silymarin phosphatide complexes as claimed in claim 5 of 25 parts is joined in ultrasonic substrate afterwards, and under 400W power ultrasonic 30 minutes again, and the matrix solution that guarantees to be dissolved with silymarin phosphatide complexes by ice bath in ultrasonic middle temperature lower than 35 ° of C;
After ultrasonic immediately with the above-mentioned matrix solution that is dissolved with silymarin phosphatide complexes of infrared lamp irradiation 2 minutes; Take gelatin as capsule skin, be pressed into soft capsule, packing, obtains finished product.
10. a preparation method for Hepadestal soft capsule, is characterized in that, vegetable oil and Cera Flava are mixed to form to substrate, and this substrate is ultrasonic; Silymarin phosphatide complexes as claimed in claim 5 is joined in the substrate after ultrasonic, and again ultrasonic, and the matrix solution that guarantees to be dissolved with silymarin phosphatide complexes by ice bath in ultrasonic middle temperature lower than 35 ° of C; Ultrasonic afterwards immediately with the above-mentioned matrix solution that is dissolved with silymarin phosphatide complexes of infrared lamp irradiation; Take gelatin as capsule skin, be pressed into soft capsule, packing, obtains finished product.
The preparation method of 11. a kind of Hepadestal soft capsules as claimed in claim 10, is characterized in that step is as follows:
The vegetable oil of 70 parts, the Cera Flava of 5 parts are mixed to form to substrate, and by this substrate under 400W power ultrasonic 15 minutes;
The silymarin phosphatide complexes as claimed in claim 5 of 25 parts is joined in ultrasonic substrate afterwards, and under 400W power ultrasonic 30 minutes again, and the matrix solution temperature that guarantees to be dissolved with silymarin phosphatide complexes by ice bath in ultrasonic lower than 35 ° of C;
After ultrasonic immediately with the above-mentioned matrix solution that is dissolved with silymarin phosphatide complexes of infrared lamp irradiation 2 minutes; Take gelatin as capsule skin, be pressed into soft capsule, packing, obtains finished product.
The preparation method of 12. a kind of Hepadestal soft capsules as claimed in claim 11, is characterized in that: described vegetable oil is one or several of soybean oil, Oleum Cocois, Oleum Camelliae, vegetable oil.
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| WO2016150380A1 (en) * | 2015-03-23 | 2016-09-29 | 天士力制药集团股份有限公司 | Pharmaceutical composition containing silybin |
| CN105983014A (en) * | 2015-03-23 | 2016-10-05 | 天士力制药集团股份有限公司 | Medicine composition containing silibinin, VE and L-carnitine |
| CN113197877A (en) * | 2021-04-02 | 2021-08-03 | 海南普利制药股份有限公司 | Pharmaceutical composition comprising silymarin |
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| WO2016150380A1 (en) * | 2015-03-23 | 2016-09-29 | 天士力制药集团股份有限公司 | Pharmaceutical composition containing silybin |
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