CN103751798A - Silybin-phospholipid complex and preparation method thereof - Google Patents
Silybin-phospholipid complex and preparation method thereof Download PDFInfo
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- CN103751798A CN103751798A CN201410039303.4A CN201410039303A CN103751798A CN 103751798 A CN103751798 A CN 103751798A CN 201410039303 A CN201410039303 A CN 201410039303A CN 103751798 A CN103751798 A CN 103751798A
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Abstract
The invention relates to the field of chemical preparation and dosage form modification, in particular to a silybin-phospholipid complex and a preparation process thereof and a silybin-phospholipid complex soft capsule prepared from the complex. According to the silybin-phospholipid complex and the preparation process, a phospholipid complex is prepared from silybin, so that the water solubility of the silybin is greatly improved, the lipid solubility and water solubility of the obtained complex are balanced, and the bioavailability is greatly improved; moreover, the silybin-phospholipid complex soft capsules prepared from the complex also have high bioavailability, and are convenient to take; the utilization of the silybin is greatly promoted.
Description
Technical field
The present invention relates to technical field of medicine, relate in particular to silybin-phospholipid complex and preparation technology thereof, and the silybin-phospholipid complex soft capsule preparing with this complex.
Background technology
Silymarin be from feverfew Herba Silybi mariani (pale reddish brown) (
silybum marianum(L.) Gaertn) seed in extract a kind of flavone compound of 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 people with it treat 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.
And main active in the middle of silymarin is silibinin, pharmacology, toxicological test result show, silibinin has the effect of obvious protection and stable liver plasma membrane; The all kinds hepatic injury that the hepatotoxic agents such as carbon tetrachloride, thioacetamide, muscarine, phallodine, mucronatine are caused has protection and therapeutical effect in various degree, and the rising of the caused alanine aminotransferase of carbon tetrachloride is had to certain interception.Be applicable to chronic persistent hepatitis, chronic active hepatitis, the treatment that first cirrhosis, liver poisoning etc. are sick.Clinic trial is in acute hepatitis, chronic hepatitis patient, and symptom, sign, liver function all have clear improvement.
Silibinin is in the market fat-soluble good, poorly water-soluble, and oral administration biaavailability is low, therefore needs to take certain technique to obtain water solublity and the fat-soluble silibinin 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 exactly phospholipid complex technique to prepare silybin-phospholipid complex and prepares soft capsule as raw material.
Summary of the invention
First technical problem to be solved by this invention is to provide a kind of silybin-phospholipid complex, silibinin and phospholipid are prepared into complex, improved the water solublity of silibinin, acquisition has water solublity and fat-soluble silybin-phospholipid complex concurrently, improves the oral administration biaavailability of silibinin.
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, silibinin 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 silybin-phospholipid complex dry product again.
Further, the preparation method of silybin-phospholipid complex, step is as follows:
(1) silibinin is dissolved in and forms solution in the middle of the ethanol of 20 times of quality and under 400 W power, 50 ° of C ultrasonic 45 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 silibinin 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 60 ° of C heating 1h, ice bath cool overnight immediately after heating;
(3) the above-mentioned mixed solution of use infrared lamp irradiation 10 minutes, then reduction vaporization, removal ethanol, after treating the complete evaporate to dryness of solvent, more 45 ° of C forced air dryings obtain silybin-phospholipid complex dry product.
Second technical problem to be solved by this invention is to provide a kind of soft capsule being comprised of silybin-phospholipid complex, by silybin-phospholipid complex 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 silybin-phospholipid complex and other matrix group, the shared percentage by weight of silybin-phospholipid complex is 25%, and the percentage by weight of the described each component of other substrate is: PEG400 is 45%, polyethylene glycol 6000 is 5%, glycerol is 25%.
Or soft capsule is become by silybin-phospholipid complex and other matrix group, the shared percentage by weight of silybin-phospholipid complex is 25%, and the percentage by weight of the described each component of other substrate is: vegetable oil 73%, Cera Flava are 2%.Vegetable oil of the present invention is one or several of soybean oil, Oleum Cocois, Oleum Camelliae, vegetable oil.
Silibinin soft capsule preparation method of the present invention is for to be mixed to form substrate by PEG400, polyethylene glycol 6000 and glycerol, and by ultrasonic this substrate; Silybin-phospholipid complex 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 silybin-phospholipid complex 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 silybin-phospholipid complex 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 silibinin soft capsule, is characterized in that step is as follows:
(1) PEG400 of 45 parts, the polyethylene glycol 6000 of 5 parts and the glycerol of 25 parts are mixed to form to substrate, and by this substrate under 400W power ultrasonic 15 minutes;
(2) silybin-phospholipid complex as claimed in claim 5 of 25 parts is joined in ultrasonic substrate afterwards, and under 400W power ultrasonic 15 minutes again, and the matrix solution that guarantees to be dissolved with silybin-phospholipid complex by ice bath in ultrasonic middle temperature lower than 35 ° of C;
(3) after ultrasonic immediately with the above-mentioned matrix solution that is dissolved with silybin-phospholipid complex of infrared lamp irradiation 2 minutes; Take gelatin as capsule skin, be pressed into soft capsule, packing, obtains finished product.
Or silibinin soft capsule preparation method of the present invention is for to be mixed to form substrate by vegetable oil and Cera Flava, and by ultrasonic this substrate; Silybin-phospholipid complex 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 silybin-phospholipid complex 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 silybin-phospholipid complex 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 silibinin soft capsule, is characterized in that step is as follows:
(1) vegetable oil of 73 parts, the Cera Flava of 2 parts are mixed to form to substrate, and by this substrate under 400W power ultrasonic 15 minutes;
(2) silybin-phospholipid complex as claimed in claim 5 of 25 parts is joined in ultrasonic substrate afterwards, and under 400W power ultrasonic 15 minutes again, and the matrix solution temperature that guarantees to be dissolved with silybin-phospholipid complex by ice bath in ultrasonic lower than 35 ° of C;
(3) after ultrasonic immediately with the above-mentioned matrix solution that is dissolved with silybin-phospholipid complex 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 silibinin 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 silibinin
29.2 grams, the dry powder of the silymarin that embodiment 2 is prepared joins in the ethanol water of 85% mass concentration of 87.6 grams, 70 degrees Celsius of reflux 1 hour, then standing 24 hours, standing liquid is being obtained to precipitate with precipitate for Fen Li 3 hours with seperator, then precipitate is laid in the middle of rustless steel drip pan, 80 degrees Celsius of vacuum dryings 3 hours, pulverize and obtain 7.3 grams, the dry powder of silibinin.
the preparation of embodiment 4 silybin-phospholipid complexes
The silibinin that 10 grams of embodiment 3 are prepared is dissolved in and forms solution in the middle of 200 grams of ethanol and under 400 W power, 50 ° of C ultrasonic 45 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 60 ° of C heating 1h, ice bath cool overnight immediately after heating.With the above-mentioned mixed solution of infrared lamp irradiation 10 minutes, then reduction vaporization, remove ethanol, after treating the complete evaporate to dryness of solvent, more 45 ° of C forced air dryings obtain 51.6 grams of silybin-phospholipid complex dry products.
the preparation of embodiment 5 silybin-phospholipid complexes
The silibinin that 10 grams of embodiment 3 are prepared is dissolved in and forms solution in the middle of 200 grams of ethanol and under 400 W power, 50 ° of C ultrasonic 45 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 60 ° of C heating 1h, ice bath cool overnight immediately after heating.With the above-mentioned mixed solution of infrared lamp irradiation 10 minutes, then reduction vaporization, remove ethanol, after treating the complete evaporate to dryness of solvent, more 45 ° of C forced air dryings obtain 54.9 grams of silybin-phospholipid complex dry products.
the preparation of embodiment 6 silybin-phospholipid complexes
The silibinin that 10 grams of embodiment 3 are prepared is dissolved in and forms solution in the middle of 200 grams of ethanol and under 400 W power, 50 ° of C ultrasonic 45 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 60 ° of C heating 1h, ice bath cool overnight immediately after heating.With the above-mentioned mixed solution of infrared lamp irradiation 10 minutes, then reduction vaporization, remove ethanol, after treating the complete evaporate to dryness of solvent, more 45 ° of C forced air dryings obtain 56.1 grams of silybin-phospholipid complex dry products.
the preparation of embodiment 7 silybin-phospholipid complexes
The silibinin that 10 grams of embodiment 3 are prepared is dissolved in and forms solution in the middle of 200 grams of ethanol and under 400 W power, 50 ° of C ultrasonic 45 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 60 ° of C heating 1h, ice bath cool overnight immediately after heating.With the above-mentioned mixed solution of infrared lamp irradiation 10 minutes, then reduction vaporization, remove ethanol, after treating the complete evaporate to dryness of solvent, more 45 ° of C forced air dryings obtain 53.3 grams of silybin-phospholipid complex dry products.
the preparation of embodiment 8 silybin-phospholipid complexes
The silibinin that 10 grams of embodiment 3 are prepared is dissolved in and forms solution in the middle of 200 grams of ethanol and under 400 W power, 50 ° of C ultrasonic 45 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 60 ° of C heating 1h, ice bath cool overnight immediately after heating.With the above-mentioned mixed solution of infrared lamp irradiation 10 minutes, then reduction vaporization, remove ethanol, after treating the complete evaporate to dryness of solvent, more 45 ° of C forced air dryings obtain 57.2 grams of silybin-phospholipid complex dry products.
the preparation of embodiment 9 silybin-phospholipid complexes
The silibinin that 10 grams of embodiment 3 are prepared is dissolved in and forms solution in the middle of 200 grams of ethanol and under 400 W power, 50 ° of C ultrasonic 45 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 60 ° of C heating 1h, ice bath cool overnight immediately after heating.With the above-mentioned mixed solution of infrared lamp irradiation 10 minutes, then reduction vaporization, remove ethanol, after treating the complete evaporate to dryness of solvent, more 45 ° of C forced air dryings obtain 59.3 grams of silybin-phospholipid complex dry products.
the preparation of embodiment 10 silybin-phospholipid complexes
The silibinin that 10 grams of embodiment 3 are prepared is dissolved in and forms solution in the middle of 200 grams of ethanol and under 400 W power, 50 ° of C ultrasonic 45 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 60 ° of C heating 1h, ice bath cool overnight immediately after heating.With the above-mentioned mixed solution of infrared lamp irradiation 10 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 silybin-phospholipid complex dry products.
the preparation of embodiment 11 silibinin soft capsules
The PEG400 of 45 grams, the polyethylene glycol 6000 of 5 grams and the glycerol of 25 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 silibinin join in the substrate after ultrasonic, and under 400W power ultrasonic 15 minutes again, and the matrix solution temperature that guarantees the phosphatide complexes that is dissolved with silibinin by ice bath in ultrasonic lower than 35 ° of C.After ultrasonic immediately with the above-mentioned matrix solution that is dissolved with silybin-phospholipid complex 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 silibinin soft capsules
The PEG400 of 45 grams, the polyethylene glycol 6000 of 5 grams and the glycerol of 25 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 silibinin join in the substrate after ultrasonic, and under 400W power ultrasonic 15 minutes again, and the matrix solution temperature that guarantees the phosphatide complexes that is dissolved with silibinin by ice bath in ultrasonic lower than 35 ° of C.After ultrasonic immediately with the above-mentioned matrix solution that is dissolved with silybin-phospholipid complex 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 silibinin soft capsules
The PEG400 of 45 grams, the polyethylene glycol 6000 of 5 grams and the glycerol of 25 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 silibinin join in the substrate after ultrasonic, and under 400W power ultrasonic 15 minutes again, and the matrix solution temperature that guarantees the phosphatide complexes that is dissolved with silibinin by ice bath in ultrasonic lower than 35 ° of C.After ultrasonic immediately with the above-mentioned matrix solution that is dissolved with silybin-phospholipid complex 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 silibinin soft capsules
The PEG400 of 45 grams, the polyethylene glycol 6000 of 5 grams and the glycerol of 25 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 silibinin join in the substrate after ultrasonic, and under 400W power ultrasonic 15 minutes again, and the matrix solution temperature that guarantees the phosphatide complexes that is dissolved with silibinin by ice bath in ultrasonic lower than 35 ° of C.After ultrasonic immediately with the above-mentioned matrix solution that is dissolved with silybin-phospholipid complex 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 silibinin soft capsules
The PEG400 of 45 grams, the polyethylene glycol 6000 of 5 grams and the glycerol of 25 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 silibinin join in the substrate after ultrasonic, and under 400W power ultrasonic 15 minutes again, and the matrix solution temperature that guarantees the phosphatide complexes that is dissolved with silibinin by ice bath in ultrasonic lower than 35 ° of C.After ultrasonic immediately with the above-mentioned matrix solution that is dissolved with silybin-phospholipid complex 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 silibinin soft capsules
The PEG400 of 45 grams, the polyethylene glycol 6000 of 5 grams and the glycerol of 25 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 silibinin join in the substrate after ultrasonic, and under 400W power ultrasonic 15 minutes again, and the matrix solution temperature that guarantees the phosphatide complexes that is dissolved with silibinin by ice bath in ultrasonic lower than 35 ° of C.After ultrasonic immediately with the above-mentioned matrix solution that is dissolved with silybin-phospholipid complex 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 silibinin soft capsules
The PEG400 of 45 grams, the polyethylene glycol 6000 of 5 grams and the glycerol of 25 grams are mixed to form to substrate, and by this substrate under 400W power ultrasonic 15 minutes.By the embodiment of 25 grams
10 preparethe phosphatide complexes of silibinin join in the substrate after ultrasonic, and under 400W power ultrasonic 15 minutes again, and the matrix solution temperature that guarantees the phosphatide complexes that is dissolved with silibinin by ice bath in ultrasonic lower than 35 ° of C.After ultrasonic immediately with the above-mentioned matrix solution that is dissolved with silybin-phospholipid complex 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 silibinin soft capsules
The Cera Flava of the soybean oil of 73 grams and 2 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 silibinin join in the substrate after ultrasonic, and under 400W power ultrasonic 15 minutes again, and the matrix solution temperature that guarantees the phosphatide complexes that is dissolved with silibinin by ice bath in ultrasonic lower than 35 ° of C.After ultrasonic immediately with the above-mentioned matrix solution that is dissolved with silybin-phospholipid complex 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 silibinin soft capsules
The Cera Flava of the Oleum Camelliae of 73 grams and 2 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 silibinin join in the substrate after ultrasonic, and under 400W power ultrasonic 15 minutes again, and the matrix solution temperature that guarantees the phosphatide complexes that is dissolved with silibinin by ice bath in ultrasonic lower than 35 ° of C.After ultrasonic immediately with the above-mentioned matrix solution that is dissolved with silybin-phospholipid complex 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 silibinin soft capsules
The Cera Flava of the vegetable oil of 73 grams and 2 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 silibinin join in the substrate after ultrasonic, and under 400W power ultrasonic 15 minutes again, and the matrix solution temperature that guarantees the phosphatide complexes that is dissolved with silibinin by ice bath in ultrasonic lower than 35 ° of C.After ultrasonic immediately with the above-mentioned matrix solution that is dissolved with silybin-phospholipid complex 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 silibinin soft capsules
The Cera Flava of the Oleum Cocois of 73 grams and 2 grams is 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 silibinin join in the substrate after ultrasonic, and under 400W power ultrasonic 15 minutes again, and the matrix solution temperature that guarantees the phosphatide complexes that is dissolved with silibinin by ice bath in ultrasonic lower than 35 ° of C.After ultrasonic immediately with the above-mentioned matrix solution that is dissolved with silybin-phospholipid complex 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 silibinin soft capsules
The vegetable oil of 35 grams, the soybean oil of 38 grams and the Cera Flava of 2 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 silibinin join in the substrate after ultrasonic, and under 400W power ultrasonic 15 minutes again, and the matrix solution temperature that guarantees the phosphatide complexes that is dissolved with silibinin by ice bath in ultrasonic lower than 35 ° of C.After ultrasonic immediately with the above-mentioned matrix solution that is dissolved with silybin-phospholipid complex 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 silibinin soft capsules
The Oleum Cocois of 35 grams, the Oleum Camelliae of 38 grams and the Cera Flava of 2 grams are mixed to form to substrate, and by this substrate under 400W power ultrasonic 15 minutes.The phosphatide complexes of the silibinin that the embodiment of 25 grams 9 is prepared joins in ultrasonic substrate afterwards, and under 400W power ultrasonic 15 minutes again, and the matrix solution temperature that guarantees the phosphatide complexes that is dissolved with silibinin by ice bath in ultrasonic lower than 35 ° of C.After ultrasonic immediately with the above-mentioned matrix solution that is dissolved with silybin-phospholipid complex 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 silibinin soft capsules
The soybean oil of 30 grams, the Oleum Cocois of 23 grams, the Oleum Camelliae of 20 grams and the Cera Flava of 2 grams are mixed to form to substrate, and by this substrate under 400W power ultrasonic 15 minutes.The phosphatide complexes of the silibinin that the embodiment of 25 grams 10 is prepared joins in ultrasonic substrate afterwards, and under 400W power ultrasonic 15 minutes again, and the matrix solution temperature that guarantees the phosphatide complexes that is dissolved with silibinin by ice bath in ultrasonic lower than 35 ° of C.After ultrasonic immediately with the above-mentioned matrix solution that is dissolved with silybin-phospholipid complex 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 silibinin soft capsules
The soybean oil of 30 grams, the vegetable oil of 23 grams, the Oleum Camelliae of 20 grams and the Cera Flava of 2 grams are mixed to form to substrate, and by this substrate under 400W power ultrasonic 15 minutes.The phosphatide complexes of the silibinin that the embodiment of 25 grams 5 is prepared joins in ultrasonic substrate afterwards, and under 400W power ultrasonic 15 minutes again, and the matrix solution temperature that guarantees the phosphatide complexes that is dissolved with silibinin by ice bath in ultrasonic lower than 35 ° of C.After ultrasonic immediately with the above-mentioned matrix solution that is dissolved with silybin-phospholipid complex 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 silibinin soft capsules
The soybean oil of 20 grams, the vegetable oil of 23 grams, the Oleum Camelliae of 20 grams, the Oleum Cocois of 10 grams and the Cera Flava of 2 grams are mixed to form to substrate, and by this substrate under 400W power ultrasonic 15 minutes.The phosphatide complexes of the silibinin that the embodiment of 25 grams 7 is prepared joins in ultrasonic substrate afterwards, and under 400W power ultrasonic 15 minutes again, and the matrix solution temperature that guarantees the phosphatide complexes that is dissolved with silibinin by ice bath in ultrasonic lower than 35 ° of C.After ultrasonic immediately with the above-mentioned matrix solution that is dissolved with silybin-phospholipid complex 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 27 silibinin soft capsules
The soybean oil of 20 grams, the vegetable oil of 23 grams, the Oleum Camelliae of 20 grams, the Oleum Cocois of 10 grams and the Cera Flava of 2 grams are mixed to form to substrate, and by this substrate under 400W power ultrasonic 15 minutes.The phosphatide complexes of the silibinin that the embodiment of 25 grams 9 is prepared joins in ultrasonic substrate afterwards, and under 400W power ultrasonic 15 minutes again, and the matrix solution temperature that guarantees the phosphatide complexes that is dissolved with silibinin by ice bath in ultrasonic lower than 35 ° of C.After ultrasonic immediately with the above-mentioned matrix solution that is dissolved with silybin-phospholipid complex 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 silybin-phospholipid complex, it is characterized in that: in the middle of silibinin 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 silybin-phospholipid complex dry product.
2. the preparation method of silybin-phospholipid complex as claimed in claim 1, is characterized in that step is as follows:
Silibinin is dissolved in and forms solution in the middle of the ethanol of 20 times of quality and under 400 W power, 50 ° of C ultrasonic 45 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 silibinin 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 60 ° of C heating 1h, ice bath cool overnight immediately after heating;
With the above-mentioned mixed solution of infrared lamp irradiation 10 minutes, then reduction vaporization, remove ethanol, after treating the complete evaporate to dryness of solvent, more 45 ° of C forced air dryings obtain silybin-phospholipid complex dry product.
3. the preparation method of silybin-phospholipid complex 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 silybin-phospholipid complex 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. silybin-phospholipid complex, is characterized by by the preparation method of the silybin-phospholipid complex described in claim 1-4 any one and prepares.
6. a silibinin soft capsule, it is characterized in that, by silybin-phospholipid complex as claimed in claim 5 and other matrix group, become, the shared percentage by weight of silybin-phospholipid complex is 25%, and the percentage by weight of the described each component of other substrate is: PEG400 is 45%, polyethylene glycol 6000 is 5%, glycerol is 25%.
7. a silibinin soft capsule, it is characterized in that, by silybin-phospholipid complex claimed in claim 5 and other matrix group, become, the shared percentage by weight of silybin-phospholipid complex is 25%, and the percentage by weight of the described each component of other substrate is: vegetable oil 73%, Cera Flava are 2%.
8. a preparation method for silibinin soft capsule, is characterized in that, PEG400, polyethylene glycol 6000 and glycerol are mixed to form to substrate, and by ultrasonic this substrate; Silybin-phospholipid complex 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 silybin-phospholipid complex 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 silybin-phospholipid complex 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 silibinin soft capsule as claimed in claim 8, is characterized in that step is as follows:
The PEG400 of 45 parts, the polyethylene glycol 6000 of 5 parts and the glycerol of 25 parts are mixed to form to substrate, and by this substrate under 400W power ultrasonic 15 minutes;
The silybin-phospholipid complex as claimed in claim 5 of 25 parts is joined in ultrasonic substrate afterwards, and under 400W power ultrasonic 15 minutes again, and the matrix solution that guarantees to be dissolved with silybin-phospholipid complex 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 silybin-phospholipid complex 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 silibinin soft capsule, is characterized in that, vegetable oil and Cera Flava are mixed to form to substrate, and by ultrasonic this substrate; Silybin-phospholipid complex 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 silybin-phospholipid complex 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 silybin-phospholipid complex 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 silibinin soft capsules as claimed in claim 10, is characterized in that step is as follows:
The vegetable oil of 73 parts, the Cera Flava of 2 parts are mixed to form to substrate, and by this substrate under 400W power ultrasonic 15 minutes;
The silybin-phospholipid complex as claimed in claim 5 of 25 parts is joined in ultrasonic substrate afterwards, and under 400W power ultrasonic 15 minutes again, and the matrix solution temperature that guarantees to be dissolved with silybin-phospholipid complex by ice bath in ultrasonic lower than 35 ° of C;
After ultrasonic immediately with the above-mentioned matrix solution that is dissolved with silybin-phospholipid complex 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 silibinin 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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| CN105918734A (en) * | 2016-05-17 | 2016-09-07 | 江苏健佳药业有限公司 | Silybin health-care beverage and preparation method |
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| US10307396B2 (en) | 2015-03-23 | 2019-06-04 | Tasly Pharmaceutical Group Co., Ltd. | Pharmaceutical composition containing silybin, VE and L-carnitine |
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| WO2016150375A1 (en) * | 2015-03-23 | 2016-09-29 | 天士力制药集团股份有限公司 | Pharmaceutical composition containing silibinin |
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| CN105853374A (en) * | 2016-04-26 | 2016-08-17 | 江苏中兴药业有限公司 | Preparation method of silybin-phospholipid complex |
| CN105918734A (en) * | 2016-05-17 | 2016-09-07 | 江苏健佳药业有限公司 | Silybin health-care beverage and preparation method |
| CN114146085A (en) * | 2021-12-02 | 2022-03-08 | 江苏海洋大学 | Preparation method of silybin-polyene phosphatidylcholine compound |
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