WO2016008443A1 - 含有16种甘油酯的薏苡仁油、制剂及其应用 - Google Patents
含有16种甘油酯的薏苡仁油、制剂及其应用 Download PDFInfo
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- A61K31/215—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids
- A61K31/22—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids of acyclic acids, e.g. pravastatin
- A61K31/23—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids of acyclic acids, e.g. pravastatin of acids having a carboxyl group bound to a chain of seven or more carbon atoms
- A61K31/231—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids of acyclic acids, e.g. pravastatin of acids having a carboxyl group bound to a chain of seven or more carbon atoms having one or two double bonds
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- A61K31/215—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids
- A61K31/22—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids of acyclic acids, e.g. pravastatin
- A61K31/23—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids of acyclic acids, e.g. pravastatin of acids having a carboxyl group bound to a chain of seven or more carbon atoms
- A61K31/232—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids of acyclic acids, e.g. pravastatin of acids having a carboxyl group bound to a chain of seven or more carbon atoms having three or more double bonds, e.g. etretinate
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- A61K47/24—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing atoms other than carbon, hydrogen, oxygen, halogen, nitrogen or sulfur, e.g. cyclomethicone or phospholipids
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Definitions
- the invention relates to the field of pharmacy, in particular to a coix seed oil, a preparation, a preparation method thereof and application thereof in preparing an antitumor drug.
- Coix seed is a mature dry seed of Coix lacryma-jobi L.var ma-yuen (Roman.) Stapf. It is a diuretic drug for a long time. Modern research has found that Coix seed has pharmacological effects such as analgesic, anti-inflammatory, immune regulation, anti-ulcer, hypolipidemic and weight loss. In recent years, domestic and foreign scholars have studied the chemical constituents of Coix seed by TLC, HPLC, GC and other methods, and found that it contains a variety of active ingredients, including coix seed esters, triglycerides, fatty acids, lactams, Compounds such as barley lactones, sugars, sterols, and triterpenoids.
- active ingredients including coix seed esters, triglycerides, fatty acids, lactams, Compounds such as barley lactones, sugars, sterols, and triterpenoids.
- esters are the first to be found to have anti-tumor activity, and are also the most reported chemical components.
- Kanglaite injection which is currently used as an active ingredient in Chinese herbal medicine, has been widely used, its use of coix seed oil is complicated, and contains triglyceride and diglyceride in addition to triglyceride. And fatty acid esters, etc., which will inevitably pose great challenges to quality control and clinical drug safety in the actual production process.
- the invention uses the hazelnut powder as a raw material, adopts the steps of supercritical carbon dioxide extraction, alkalization, neutral alumina and kaolin purification to obtain an effective part of coix seed oil; by separating and identifying the active components thereof, it is determined.
- the composition is mainly composed of eleven triglyceride components and five diglyceride components. Further, the physical and chemical constants are detected, and the optimal acid value, iodine value, saponification value, refractive index and relative density are determined.
- the use of the herb of the present invention for the determination of the composition and composition of the coix seed oil ensures the quality stability between the batches in the industrial production, and also avoids the toxic side reaction caused by the complicated composition of the coix seed oil.
- the object of the present invention is to provide a coix seed oil extracted from coix seed, which is characterized in that the coix seed oil contains five kinds of diglyceride components and 11 triglyceride components in the following mass percentages: 1,3-dioleic acid glyceride 0.40-0.58%, 1-linoleic acid-3-oleic acid diglyceride 0.91 ⁇ 1.31%, 1,2-dioleic acid glyceride 0.24-0.35%, 1-oleic acid -2-linoleic acid diglyceride 0.66-0.95%, 1,2-dilinoleic acid glyceride 0.33-0.47%, trilinoleic acid glyceride 4.87-6.99%, 1-oleic acid-2,3-di Glycerol glyceride 13.00 ⁇ 18.69%, 1-palmitic acid-2,3-dilinoleic acid glyceride 5.25 ⁇ 7.54%, 1,3-dioleic acid-2-linoleic acid
- the mass percentage of the above five diglyceride components and 11 triglyceride components is: 1,3-dioleic acid glyceride 0.45-0.55%, 1-linoleic acid-3-oleic acid glycerol Ester 1.03 to 1.25%, 1,2-dioleic acid glyceride 0.27 to 0.33%, 1-oleic acid-2-linoleic acid diglyceride 0.75 to 0.91%, 1,2-dilinoleic acid glyceride 0.37 ⁇ 0.45%, linoleic acid glyceride 5.47-6.69%, 1-oleic acid-2,3-dilinoleic acid glyceride 14.63 ⁇ 17.88%, 1-palmitic acid-2,3-dilinoleic acid glyceride 5.9 ⁇ 7.21%, 1,3-dioleic acid-2-linoleic acid glyceride 14.88 ⁇ 18.19%, 1-palmitic acid-2-linoleic acid
- the mass percentage of the above five diglyceride components and the eleven triglyceride components is: 1,3-dioleic acid glyceride 0.49 to 0.51%, 1-linoleic acid-3-oleic acid glycerin Diester 1.12 to 1.16%, 1,2-dioleic acid glyceride 0.29 to 0.31%, 1-oleic acid-2-linoleic acid diglyceride 0.81 to 0.85%, 1,2-dilinoleic acid glyceride 0.40 ⁇ 0.42%, linoleic acid glyceride 5.96 ⁇ 6.20%, 1-oleic acid-2,3-dilinoleic acid glyceride 15.93 ⁇ 16.58%, 1-palmitic acid-2,3-dilinoleic acid glyceride 6.43 ⁇ 6.69%, 1,3-two Oleic acid-2-linoleic acid glyceride 16.20 ⁇ 16.87%, 1-palmitic acid-2-linoleic acid
- the above content refers to the mass percentage of the diglyceride or triglyceride compound in the coix seed oil, and the coix seed oil prepared by the method of the invention is used as a raw material, and five diglyceride monomers are obtained by preparative chromatography. The compound and 11 triglyceride monomer compounds were weighed and calculated. It can also be derived according to conventional analytical methods in the art.
- the physicochemical constant of the eucalyptus oil is as follows: a relative density of 0.916 to 0.920 at 20 ° C, a refractive index of 1.471 to 1.474 at 20 ° C, an acid value of ⁇ 0.2, an iodine value of 100 to 106, and a saponification value of 186 to 195;
- the coix seed oil of the present invention is obtained by the following method:
- Supercritical carbon dioxide extraction the coix seed is pulverized into 20 mesh to 100 mesh, and extracted with a 600 L ⁇ 2 supercritical CO 2 extractor.
- the coix seed powder is charged into the extraction kettle, and the CO2 preheater is heated by the jacketed circulating hot water.
- the fluid enters the separation column, and the pressure of the separation column is controlled to be 7-10 Mpa, and the coix seed oil is separated; the CO 2 gas from the separation column enters the first-stage and second-stage analytical kettles, respectively, and the pressure is maintained at 5-7 Mpa and 4-6 Mpa, respectively. Discard the impurities such as moisture obtained by analysis, and the CO 2 gas is converted into liquid CO 2 through a condenser, recycled, and continuously extracted for 2 to 3 hours to obtain coix seed oil;
- Refining Take the coix seed oil obtained by supercritical CO 2 extraction, add 65% oil weight of 60 ° C ⁇ 90 ° C petroleum ether, and then add 36% ⁇ 56% oil 2% NaOH solution according to the acid value, after stirring for 10 min After standing for 18 to 24 hours, the lower layer of soap is removed, and the upper layer is washed with purified water, and after standing for 18 to 24 hours, the lower layer of wastewater is removed; the upper layer is taken for the second water washing, and after standing for 40 to 50 hours, the lower layer of wastewater is removed.
- the refining step is as follows:
- the coix seed oil obtained by supercritical CO2 extraction is added with 65% oil weight of 60 ° C ⁇ 90 ° C petroleum ether, and then according to the acid value, adding 36% ⁇ 56% oil 2% NaOH solution, stirring for 10 min, then standing After 20h, the lower layer of soap was removed, and the upper layer was washed with purified water. After standing for 22 hours, the lower layer of wastewater was removed. The upper layer was taken for the second time. After standing for 46 hours, the lower layer of wastewater was removed. The upper layer was refilled with 70% to 90%.
- % acetone was demulsified, after standing for 3 h, the lower layer of waste acetone was removed; the upper oil solution was taken, 5% activated neutral alumina was added, stirred for 30 min, and filtered; after heating the filtrate, 4% activated kaolin was added:
- Activated carbon 1:1 mixed adsorbent, stirred, incubated at 40 ⁇ 50 ° C for 30 min, filtered; filtrate reduced solvent recovery, then add purified water for water washing, after standing for 1 h, remove the lower layer of wastewater; the upper layer of oil is charged Under nitrogen conditions, it is concentrated under heating and decompression, and then sterilized by dry heat at 160-170 ° C for 2 h. After cooling, it is filtered through a 0.2 ⁇ m microporous membrane, dispensed in a 500 ml glass infusion bottle, filled with nitrogen, sealed, and obtained. .
- the coix seed oil of the invention is a pale yellow clear liquid with slight gas and mild taste; it is very soluble in petroleum ether or chloroform, soluble in acetone, slightly soluble in ethanol, and insoluble in water.
- the coix seed oil prepared according to the method of the present invention is tested according to an appendix method of the Chinese Pharmacopoeia 2010 edition, and the physical and chemical constants thereof are: relative density of 0.916 to 0.920 at 20 ° C, and refractive index of 1.471 to 1.474 at 20 ° C, acid The value is ⁇ 0.2, the iodine value is 100 to 106, and the saponification value is 186 to 195.
- the acid value in the pharmacopoeia refers to the weight (mg) of potassium hydroxide required to neutralize the free fatty acid contained in 1 gram of fat, fatty oil or the like. In the quality study of oil products, The acid value is an important evaluation index.
- the acid value is less than 0.2, that is, the coix seed oil prepared by optimizing the supercritical extraction parameters and the alkalizing purification process in the preparation process.
- the invention has the following advantages: on the one hand, the free fatty acid content as an impurity is extremely low, and the finished product quality is good; on the other hand, a large amount of active components of diglyceride and triglyceride are enriched, the purity is high, and among them, diglyceride and glycerin The ester components are clear in type and stable in content.
- the preparation method of the invention has high yield, low cost, stable product, is suitable for industrial production, and is safe and controllable.
- the pharmaceutically acceptable carrier includes conventional diluents, excipients, fillers, emulsifiers, binders, lubricants, absorption enhancers, surfactants, disintegrants, lubricants or An antioxidant, if necessary, a flavoring agent, a sweetener, a preservative or a coloring agent.
- the pharmaceutically acceptable carrier may be selected from the group consisting of: mannitol, sorbitol, sodium metabisulfite, sodium hydrogen sulfite, sodium thiosulfate, cysteine hydrochloride, thioglycolic acid, methionine, soybean phospholipid, vitamin C, vitamin E , EDTA disodium, EDTA calcium sodium, monovalent alkali metal carbonate, acetate, phosphate or its aqueous solution, hydrochloric acid, acetic acid, sulfuric acid, phosphoric acid, amino acid, sodium chloride, potassium chloride, sodium lactate, hydroxybenzene Ethyl ester solution, benzoic acid, potassium sorbate, chlorhexidine acetate, xylitol, maltose, glucose, fructose, dextran, glycine, starch, sucrose, lactose, mannitol, silicon derivatives, cellulose and Derivatives, alginate, gelatin, polyvin
- the pharmaceutical preparation may be an oral solid preparation, an oral liquid preparation or an injection.
- the oral solid preparation is selected from the group consisting of a capsule, a tablet, a dropping pill, a granule, and a concentrated pill;
- the oral liquid preparation is selected from an aqueous or oily suspension, a solution, an emulsion, a syrup or an elixir, or It is a dry product which can be formulated with water or other suitable carrier before use;
- the injection is selected from one of a nanosuspension, a liposome, an emulsion, a lyophilized powder injection and an aqueous injection.
- the injection comprises the following components: 50-350 g of the coix seed oil of the invention, 10-40 g of soybean phospholipid for injection or soybean lecithin for injection, glycerol for injection or 15-50 g of glycerin for injection, and water for injection is added. 1000ml.
- Another name is the coix seed oil, the oil ester and the water phase are separately heated to 60-70 ° C, and then placed in a high-pressure homogenizer for high-pressure emulsification.
- the emulsifier homogenizer low pressure is 5 to 12 MPa, and the high pressure is 25 to 50 MPa. Recycling homogenization 3 to 6 times, to 2 ⁇ m or less, the particles should be not less than 95%, and particles above 5 ⁇ m should not be detected. If necessary, adjust the pH to 4.8 to 8.5, preferably 6.8 to 7, preferably 6.8 with NaOH or HCl. ;
- the uniform emulsion nitrogen gas is pressurized and filtered through a microporous filter cartridge of 3 ⁇ m or less, sterilized by nitrogen filling, and cooled.
- the capsule comprises the following components: 200 to 800 g of coix seed oil, 0.20 to 0.60 g of an antioxidant and/or an emulsifier, and 1000 capsules.
- Preparation of glue Weigh the appropriate amount of gelatin, purified water, glycerin and preservative according to the weight ratio of 1:0.6 ⁇ 1.2:0.3 ⁇ 0.8:0.0001 ⁇ 0.01; sequentially add glycerin, purified water and preservative (selected from 10% hydroxybenzene) Ethyl ester solution, one of benzoic acid, potassium sorbate and chlorhexidine acetate) is added to the plastic can, heated to 70 ° C ⁇ 90 ° C, then added gelatin constantly stirred, pumped Empty until the gelatin is completely dissolved, filter the glue, store at 56-62 ° C, and set aside;
- Preparation of liquid medicine Add the formula amount of coix seed oil, antioxidant and/or emulsifier (antioxidant is vitamin E, emulsifier is Tween 80) into the batching tank, and stir constantly until it is evenly mixed;
- antioxidant is vitamin E
- emulsifier is Tween 80
- Capsule Select the appropriate pellet mold according to the size of the capsule, dry it at 15 ⁇ 30°C and relative humidity less than 35%, then remove the size pellets, then wash the pellets with 95% medicinal ethanol and continue to dry. When the water content is less than 12%, the unqualified capsules are removed by visual inspection and the package is obtained.
- the invention shows through pharmacodynamic experiments that the pharmaceutical composition and the preparation thereof have different degrees of inhibitory effects on various human tumor cell lines, and can be used as a medicine for treating tumor diseases.
- the tumor refers to early, middle or late stage lung cancer, liver cancer, pancreatic cancer, prostate cancer, ovarian cancer or breast cancer.
- compositions of the present invention and their formulations on antitumor are illustrated below by experimental data.
- Cell lines PANC-1 (human pancreatic cancer cells), SKOV3 (human ovarian cancer cells), MCF-7 (human breast cancer cells), Bcap-37 (human breast cancer cells), SMMC-7721 (human liver cancer) Cells), HepG-2 (human liver cancer cells), A549 (human lung cancer cells), H460 (human lung cancer cells), the above cell lines were preserved by the Shanghai Pharmaceutical Industry Research Pharmacological Evaluation Research Center and maintained.
- DMEM complete medium 10% newborn calf serum (GIBCO BRL), double antibody was added.
- Trypsin purchased from Invitrogen, stored at -20 °C.
- PBS Phosphate buffer
- MTT (AMRESCO) solution A solution of 5 mg/ml was prepared with PBS.
- Dissolving solution 10 ml of SDS, 5 ml of isobutanol and 0.1 ml of concentrated hydrochloric acid per 100 ml of deionized double distilled water.
- the inhibitory effect of the sample on the above cell line was measured by the MTT method.
- Cell culture 1 The cells were taken out from liquid nitrogen, rapidly thawed in a 37 ° C water bath, and the cells were transferred to a 10 ml sterile centrifuge tube in a sterile table to add 6 ml of the cell culture medium, and centrifuged at 1000 rpm for 5 minutes. Discard the supernatant, add 5-6 ml of cell culture medium to the pellet, pipette it to suspend it, transfer it to the cell culture flask, and place it in a 37 °C cell culture incubator.
- the cells are trypsinized and washed, suspended in a medium containing 10% calf serum, counted by the trypan blue staining method, and the cell suspension is adjusted.
- the density is 2 x 10 5 cells/ml.
- Supercritical carbon dioxide extraction the coix seed is pulverized into 70 mesh, extracted with a 600L ⁇ 2 supercritical CO 2 extractor, and the coix seed powder is charged into the extraction kettle, and the CO 2 preheater and the extraction kettle are heated by the jacketed circulating hot water.
- the extraction temperature and separation temperature are respectively 40 ° C and 45 ° C, maintaining the outlet temperature of the first stage analytical reactor and the secondary analytical reactor are 50 ° C and 35 ° C respectively;
- liquid CO 2 is added by high pressure pump at a flow rate of 2 t / h Pressed into the CO 2 preheater to become a fluid in supercritical state, enter the extraction kettle, maintain the pressure of 20Mpa, extract the coix seed oil;
- the CO 2 fluid dissolved in the coix seed oil enters the separation column, controls the separation column pressure 7Mpa, and separates Coix seed oil;
- the CO 2 gas from the separation column enters the primary and secondary analytical reactors, respectively, and maintains the pressures of 7Mpa and 6Mpa respectively, discards the impurities such as water obtained by analysis, and the CO 2 gas becomes liquid CO 2 through the condenser. , recycling, continuous extraction for 2.5h, to obtain coix seed oil;
- Refining Take the coix seed oil obtained by supercritical CO 2 extraction, add 65% oil by weight of 60 ° C petroleum ether, and then add 45% NaOH solution with oil weight of 45% according to the acid value, stir for 10 min, and let stand for 20 h.
- the lower layer of soap was removed, and the upper layer was washed with purified water, and after standing for 22 hours, the lower layer of wastewater was removed; the upper layer was taken for the second time, and after standing for 46 hours, the lower layer of wastewater was removed; the upper layer was weighed with 80% acetone and demulsified.
- Supercritical carbon dioxide extraction the coix seed is pulverized into 60 mesh, extracted by a 600L ⁇ 2 supercritical CO 2 extractor, and the coix seed powder is charged into the extraction kettle, and the CO 2 preheater and the extraction kettle are heated by the jacketed circulating hot water.
- the extraction temperature and separation temperature are respectively 40 ° C and 40 ° C, maintaining the outlet temperature of the first stage analytical reactor and the secondary analytical reactor are 20 ° C and 15 ° C respectively;
- liquid CO 2 is pumped at a flow rate of 1 t / h by high pressure pump Pressed into the CO 2 preheater, became the fluid in the supercritical state, entered the extraction kettle, maintained the pressure of 22Mpa, extracted the coix seed oil;
- the CO 2 fluid dissolved in the coix seed oil entered the separation column, controlled the separation column pressure 8Mpa, and separated Coix seed oil;
- CO 2 gas from the separation column enters the first-stage and second-stage analytical reactors, respectively, and maintains the pressures of 6Mpa and 5Mpa respectively, discards the impurities such as water obtained by analysis, and the CO 2 gas becomes liquid CO 2 through the condenser. , recycling, continuous extraction for 2h, to obtain coix seed oil;
- Refining Take the coix seed oil extracted by supercritical CO 2 , add 65% oil by weight of 90 ° C petroleum ether, and then add 56% 2% NaOH solution according to the acid value, stir for 10 min, and let stand for 22 h. The lower layer of soap was removed, and the upper layer was washed with purified water, and after standing for 20 hours, the lower layer of wastewater was removed; the upper layer was taken for the second time, and after standing for 48 hours, the lower layer of wastewater was removed; the upper layer was weighed with 90% acetone and demulsified.
- Supercritical carbon dioxide extraction the coix seed is pulverized into 100 mesh, extracted by a 600L ⁇ 2 supercritical CO 2 extractor, and the coix seed powder is charged into the extraction kettle, and the CO 2 preheater and the extraction kettle are heated by the jacketed circulating hot water.
- the extraction temperature and separation temperature were respectively 33 ° C and 39 ° C, maintaining the outlet temperature of the first stage analytical reactor and the secondary analytical reactor were 30 ° C and 20 ° C respectively;
- the liquid CO 2 was pumped at a flow rate of 3 t / h by high pressure pump Pressed into the CO 2 preheater to become a fluid in supercritical state, enter the extraction kettle, maintain the pressure of 19Mpa, extract the coix seed oil;
- the CO 2 fluid dissolved in the coix seed oil enters the separation column, controls the separation column pressure 9Mpa, and separates Coix seed oil;
- CO 2 gas coming out of the separation column enters the primary and secondary analytical reactors, respectively, maintaining the pressures of 5Mpa and 4Mpa, discarding the impurities such as water obtained by analysis, and the CO 2 gas is changed into liquid CO 2 through the condenser. , recycling, continuous extraction for 3h, to obtain coix seed oil;
- Refining Take the coix seed oil extracted by supercritical CO 2 , add 65% oil by weight of petroleum ether at 80 ° C, and then add 36% 2% NaOH solution according to the acid value, stir for 10 min, and let stand for 18 h. The lower layer of soap was removed, and the upper layer was washed with purified water. After standing for 18 hours, the lower layer of wastewater was removed. The upper layer was taken for the second time. After standing for 42 hours, the lower layer of wastewater was removed. The upper layer was re-emulsified with 75% acetone.
- Supercritical carbon dioxide extraction the coix seed is pulverized into 30 mesh, extracted by a 600L ⁇ 2 supercritical CO 2 extractor, and the coix seed powder is charged into the extraction kettle, and the CO 2 preheater and the extraction kettle are heated by the jacketed circulating hot water.
- the extraction temperature and separation temperature are respectively 35 ° C and 42 ° C, maintaining the outlet temperature of the first stage analytical reactor and the secondary analytical reactor are respectively 40 ° C and 30 ° C;
- liquid CO 2 is passed through the high pressure pump at a flow rate of 1.5 t / h Pressurized into the CO 2 preheater, become the fluid in the supercritical state, enter the extraction kettle, maintain the pressure 21Mpa, extract the coix seed oil;
- the CO 2 fluid dissolved in the coix seed oil enters the separation column, and controls the separation column pressure 10Mpa, separation
- separation The coix seed oil is obtained;
- the CO 2 gas coming out of the separation column enters the primary and secondary analytical reactors successively, and the pressures are maintained at 7 MPa and 5 MPa, respectively, and the impurities such as water obtained by the analysis are discarded, and the CO 2 gas is turned into a liquid CO through the condenser. 2 , recycling, continuous extraction for 2h, to obtain coix seed oil;
- Refining Take the coix seed oil obtained by supercritical CO 2 extraction, add 65% oil by weight of 70 ° C petroleum ether, and then add 50% 2% NaOH solution according to the acid value, stir for 10 min, and let stand for 19 h. The lower layer of soap was removed, and the upper layer was washed with purified water. After standing for 21 hours, the lower layer of wastewater was removed. The upper layer was taken for the second time, and after standing for 50 hours, the lower layer of wastewater was removed. The upper layer was re-emulsified by 85% acetone.
- Supercritical carbon dioxide extraction the coix seed is pulverized into 40 mesh, extracted by a 600L ⁇ 2 supercritical CO 2 extractor, and the coix seed powder is charged into the extraction kettle, and the CO 2 preheater and the extraction kettle are heated by the jacketed circulating hot water.
- the column was separated so that the extraction temperature and the separation temperature were 42 ° C and 45 ° C, respectively, and the outlet temperatures of the first stage analytical reactor and the second stage analytical reactor were 35 ° C and 25 ° C, respectively; the liquid CO 2 was passed through the high pressure pump at a flow rate of 2.5 t / h.
- the yield was 4.3%.
- the physicochemical constant was determined as follows: Relative density of 0.916 at 20 ° C, refractive index at 20 ° C 1.473, acid number 0.14, iodine value 101, saponification value 192.
- the chromatographic peak fraction with a retention time of 15.8 min was collected, and the receiving solution was concentrated under reduced pressure at 30 ° C, transferred to a 10 ml sample vial, and nitrogen-dried at room temperature under nitrogen to obtain 1,3-dioleic acid glyceride.
- the chromatographic peak fraction with a retention time of 27 min was collected, and the receiving solution was concentrated under reduced pressure at 30 ° C, transferred to a 10 ml sample vial, and nitrogen-dried at room temperature under nitrogen to obtain 1,2-dilinoleic acid glyceride.
- mobile phase A acetonitrile
- mobile phase B acetonitrile-tetrahydrofuran (1:1)
- Mobile phase B 0 to 27 min: 50% to 60%, 27 to 35 min: 90%, 35 to 45 min: 100%
- Flow rate 18 mL/min
- UV detection wavelength 208 nm
- collected chromatographic peak fraction with retention time of 12.6 to 14.2 min concentrated under reduced pressure with a rotary evaporator under a nitrogen atmosphere, transferred to a 10 mL vial with chloroform, and dried under vacuum After drying in a box at 35 ° C for 6 h, it was filled with nitrogen gas, and the dried sample was stored in a freezer in a refrigerator to obtain tri oleic acid glyceride
- A tri linoleic acid glyceride
- B 1-oleic acid-2,3-dilinoleic acid glyceride
- C 1-palmitic acid-2,3-dilinoleic acid glyceride
- D 1, 3-Dioleic acid-2-linoleic acid glyceride
- E 1-palmitic acid-2-linoleic acid-3-oleic acid glyceride
- F 1,3-dipalmitate-2-linoleic acid glycerin Triester
- G triolein
- H 1-palmitic acid-2,3-dioleate.
- A tri linoleic acid glyceride
- B 1-oleic acid-2,3-dilinoleic acid glyceride
- C 1-palmitic acid-2,3-dilinoleic acid glyceride
- D 1, 3-Dioleic acid-2-linoleic acid glyceride
- E 1-palmitic acid-2-linoleic acid-3-oleic acid glyceride
- F 1,3-dipalmitate-2-linoleic acid glycerin Triester
- G triolein
- H 1-palmitic acid-2,3-dioleate.
- Preliminary separation was carried out by P3000A high performance liquid chromatography, mobile phase A: acetonitrile, mobile phase B: acetonitrile-tetrahydrofuran (1:1), and mobile phase B was prepared into 50 mg/mL hazelnut oil solution, each time separated.
- the mobile phase A acetonitrile
- mobile phase B acetonitrile-tetrahydrofuran (1:1)
- the above crude product was prepared into a 20 mg/mL solution using mobile phase B, and the injection volume was 1.5 mL each time;
- Superstar Benetnach TM C 18 (10 mm ⁇ 250 mm, 5 ⁇ m);
- Gradient conditions Mobile phase B: 0 to 23 min: 50% to 60%, 32 to 43 min: 60% to 90%, 43 to 60 min: 100%; flow rate: 3 mL /min; UV detection wavelength: 208nm, collect the chromatographic peak fraction with retention time of 31.2 ⁇ 34.7min, concentrate under reduced pressure with nitrogen under the protection of nitrogen, transfer to 10mL vial with chloroform, 35°C in vacuum drying oven After drying for 6 hours, nitrogen was charged, and the dried sample was stored in a freezer in a refrigerator to obtain 1-palmitic acid-2,3-dilinoleic acid glyceride monomer.
- Preliminary separation was carried out by P3000A high performance liquid chromatography, mobile phase A: acetonitrile, mobile phase B: acetonitrile-tetrahydrofuran (1:1), and mobile phase B was prepared into 50 mg/mL hazelnut oil solution, each time separated.
- Preliminary separation was carried out by P3000A high performance liquid chromatography, mobile phase A: acetonitrile, mobile phase B: acetonitrile-tetrahydrofuran (1:1), and mobile phase B was prepared into 50 mg/mL hazelnut oil solution, each time separated.
- Preliminary separation was carried out by P3000A high performance liquid chromatography, mobile phase A: acetonitrile, mobile phase B: acetonitrile-tetrahydrofuran (1:1), and mobile phase B was prepared into 50 mg/mL hazelnut oil solution, each time separated.
- the mobile phase A acetonitrile
- mobile phase B acetonitrile-tetrahydrofuran (1:1)
- the above crude product was prepared into a 20 mg/mL solution using mobile phase B, and the injection volume was 1.5 mL each time; the column: Superstar Benetnach TM C 18 (10 mm ⁇ 250 mm, 5 ⁇ m); Gradient conditions: Mobile phase B: 0 to 23 min: 50% to 60%, 32 to 43 min: 60% to 90%, 43 to 60 min: 100%; flow rate: 3 mL /min; UV detection wavelength: 208nm, collect the chromatographic peak fraction with retention time of 32.9 ⁇ 35.1min, concentrate under reduced pressure with nitrogen under the protection of nitrogen, transfer to 10mL vial with chloroform, 35°C in vacuum drying oven After drying for 6 hours, nitrogen was charged, and the dried sample was stored in a freezer in a refrigerator to obtain 1-palmitic acid-2,3-dioleate.
- the CHEETAH-HP100 high performance liquid chromatograph was used for preliminary separation.
- the injection volume was 2 mL each time.
- the preliminary separation was carried out by using CHEETAH-HP100 high performance liquid chromatography.
- the preliminary separation was carried out by using CHEETAH-HP100 high performance liquid chromatography.
- coix seed oil contains the following ingredients:
- soy lecithin for injection add appropriate amount of water for injection, disperse it to a block-free and granular solid with a high-shear dispersing emulsifier, add glycerin for injection, which is weighed according to the formula, and add water for injection. To the specified amount, stir evenly;
- Another name is the coix seed oil, the weighed oil and water are separately heated to 60 ° C, and then placed in a high-pressure homogenizer for high-pressure emulsification, the homogenizer low pressure is 6MPa, the high pressure is 30MPa, the recycling is homogeneous 4 times , the particles below 2 ⁇ m should be not less than 95%, particles above 5 ⁇ m should not be detected, if necessary, adjust the pH to 8.5 with NaOH or HCl;
- the uniform emulsion nitrogen gas is pressurized and filtered through a microporous filter filter of ⁇ 3 ⁇ m, sterilized by nitrogen filling, and cooled.
- coix seed oil contains the following ingredients:
- soy lecithin for injection add appropriate amount of water for injection, disperse it to a block-free and granular solid with a high-shear dispersing emulsifier, add glycerin for injection, which is weighed according to the formula, and add water for injection. To the specified amount, stir evenly;
- coix seed oil the oil ester and the water phase are separately heated to 70 ° C, and then placed in a high-pressure homogenizer for high-pressure emulsification, the homogenizer low pressure is 12 MPa, the high pressure is 45 MPa, and the recycling is uniform. All the particles below 2 ⁇ m should be not less than 95%, particles above 5 ⁇ m should not be detected, if necessary, adjust the pH to 7.1 with NaOH or HCl;
- the uniform emulsion nitrogen gas is pressurized and filtered through a microporous filter filter of ⁇ 3 ⁇ m, sterilized by nitrogen filling, and cooled.
- Soybean phospholipid for injection 25g
- coix seed oil contains the following ingredients:
- soy lecithin for injection add appropriate amount of water for injection, disperse it to a block-free and granular solid with a high-shear dispersing emulsifier, add glycerin for injection, which is weighed according to the formula, and add water for injection. To the specified amount, stir evenly;
- coix seed oil the oil ester and the water phase are separately heated to 65 ° C, and then placed in a high-pressure homogenizer for high-pressure emulsification.
- the emulsifier homogenizer low pressure is 10 MPa
- the high pressure is 30 MPa
- the recirculation is homogeneous 5 All the particles below 2 ⁇ m should be not less than 95%, particles above 5 ⁇ m should not be detected, if necessary, adjust the pH to 4.8 with NaOH or HCl;
- the uniform emulsion nitrogen gas is pressurized and filtered through a microporous filter filter of ⁇ 3 ⁇ m, sterilized by nitrogen filling, and cooled.
- coix seed oil contains the following ingredients:
- soy lecithin for injection add appropriate amount of water for injection, disperse it to a block-free and granular solid with a high-shear dispersing emulsifier, add glycerin for injection, which is weighed according to the formula, and add water for injection. To the specified amount, stir evenly;
- coix seed oil the oil ester and the water phase are separately heated to 68 ° C, and then placed in a high-pressure homogenizer for high-pressure emulsification.
- the emulsifier homogenizer low pressure is 7 MPa
- the high pressure is 35 MPa
- the recirculation is homogeneous 3 All the particles below 2 ⁇ m should be not less than 95%, particles above 5 ⁇ m should not be detected, if necessary, adjust the pH to 6.8 with NaOH or HCl;
- the uniform emulsion nitrogen gas is pressurized and filtered through a microporous filter filter of ⁇ 3 ⁇ m, sterilized by nitrogen filling, and cooled.
- coix seed oil contains the following ingredients:
- Preparation of glue Weigh the appropriate amount of gelatin, purified water, glycerin and 10% hydroxyethyl ester solution according to the weight ratio of 1:1.2:0.8:0.01; add glycerin, purified water and 10% hydroxyethyl ester solution to the rubber In the tank, after heating to 70 ° C, add gelatin and stir constantly, vacuum until the gelatin is completely dissolved, filter the glue, store at 60 ° C, and set aside;
- Preparation of liquid medicine Add the formula amount of coix seed oil and vitamin E into the ingredient tank, and stir constantly until it is evenly mixed;
- Capsule Select the appropriate pellets according to the size of the capsules, and then dry at 18 °C and relative humidity ⁇ 35%. After the pellets are dried, the pellets are removed, and the pellets are washed with 95% medicinal ethanol. The amount of water is less than 12%, and the unqualified capsules are removed by visual inspection.
- coix seed oil contains the following ingredients:
- 1,3-dioleic acid glyceride 0.55%
- Preparation of glue Weigh the appropriate amount of gelatin, purified water, glycerin and benzoic acid at a weight ratio of 1:1.2:0.8:0.01; add glycerin, purified water and benzoic acid to the gelatin tank in turn, heat to 90 °C, then Add gelatin, stir constantly, vacuum, Until the gelatin is completely dissolved, the glue is filtered and stored at 56 ° C for use;
- Preparation of liquid medicine Add the formula amount of coix seed oil and Tween 80 into the ingredient tank, and stir constantly until it is evenly mixed;
- Pressure capsule Select the appropriate pellet mold according to the size of the capsule, and then dry it at 26 ° C and relative humidity ⁇ 35%, then remove the size pellets, and then wash the pellets with 95% medicinal ethanol, then continue to dry to contain The amount of water is less than 12%, and the unqualified capsules are removed by visual inspection.
- coix seed oil contains the following ingredients:
- Preparation of glue Weigh the appropriate amount of gelatin, purified water, glycerin and potassium sorbate according to the weight ratio of 1:0.9:0.6:0.005; add glycerin, purified water and potassium sorbate to the gelatin tank in turn, and heat to 80 °C. Then add gelatin and stir constantly, vacuum, until the gelatin is completely dissolved, filter the glue, store at 62 ° C, and set aside;
- Preparation of liquid medicine Add the formula amount of coix seed oil and vitamin E into the ingredient tank, and stir constantly until it is evenly mixed;
- Pressure capsule select the appropriate pellet mold according to the size of the capsule, and then dry it at 28 ° C and relative humidity ⁇ 35%, then remove the size pellets, then wash the pellets with 95% medicinal ethanol, and continue to dry until The amount of water is less than 12%, and the unqualified capsules are removed by visual inspection.
- coix seed oil contains the following ingredients:
- Preparation of glue Weigh the appropriate amount of gelatin, purified water, glycerin and chlorhexidine acetate according to the weight ratio of 1:1.0:0.5:0.008; add glycerin, purified water and chlorhexidine acetate to the gelatin tank in turn, heat to 85 After °C, add gelatin and stir constantly, vacuum until the gelatin is completely dissolved, filter the glue, store at 56 °C, and set aside;
- Preparation of liquid medicine Add the formula amount of coix seed oil and Tween 80 into the ingredient tank, and stir constantly until it is evenly mixed;
- Pressure capsule select the appropriate pellet mold according to the size of the capsule, dry it at 30 ° C, relative humidity ⁇ 35%, and then remove the size pellets, then wash the pellets with 95% medicinal ethanol, and continue to dry until The amount of water is less than 12%, and the unqualified capsules are removed by visual inspection.
- coix seed oil contains the following ingredients:
- 1,3-dioleic acid-2-linoleic acid glyceride 15.01%
- soy lecithin for injection add appropriate amount of water for injection, disperse it to a block-free and granular solid with a high-shear dispersing emulsifier, add glycerin for injection, which is weighed according to the formula, and add water for injection. To the specified amount, stir evenly;
- the coix seed oil the oil and the water phase are separately heated to 60 ° C, and then placed in a high-pressure homogenizer for high-pressure emulsification.
- the homogenizer has a low pressure of 7 MPa, a high pressure of 26 MPa, and a recycling homogenization of 5 times.
- the particles below 2 ⁇ m should be not less than 95%, particles above 5 ⁇ m should not be detected, if necessary, adjust the pH to 6.8 with NaOH or HCl;
- the uniform emulsion nitrogen gas is pressurized and filtered through a microporous filter filter of ⁇ 3 ⁇ m, sterilized by nitrogen filling, and cooled.
- coix seed oil contains the following ingredients:
- soy lecithin for injection add appropriate amount of water for injection, disperse it to a block-free and granular solid with a high-shear dispersing emulsifier, add glycerin for injection, which is weighed according to the formula, and add water for injection. To the specified amount, stir evenly;
- coix seed oil the oil and the water phase are separately heated to 70 ° C, and then placed in a high-pressure homogenizer for high-pressure emulsification.
- the homogenizer low pressure is 11 MPa
- the high pressure is 48 MPa
- the recycling is homogenized 6 times.
- the particles below 2 ⁇ m should be not less than 95%
- particles above 5 ⁇ m should not be detected, if necessary, adjust the pH to 7.5 with NaOH or HCl;
- the uniform emulsion nitrogen gas is pressurized and filtered through a microporous filter filter of ⁇ 3 ⁇ m, sterilized by nitrogen filling, and cooled.
- Soybean phospholipid for injection 25g
- coix seed oil contains the following ingredients:
- soy lecithin for injection add appropriate amount of water for injection, disperse it to a block-free and granular solid with a high-shear dispersing emulsifier, add glycerin for injection, which is weighed according to the formula, and add water for injection. To the specified amount, stir evenly;
- coix seed oil the oil and the water phase are separately heated to 65 ° C, and then placed in a high-pressure homogenizer for high-pressure emulsification.
- the emulsifier homogenizer low pressure is 8 MPa
- the high pressure is 40 MPa
- the recirculation is homogeneous 4 times.
- the particles below 2 ⁇ m should be not less than 95%
- particles above 5 ⁇ m should not be detected, if necessary, adjust the pH to 6.5 with NaOH or HCl;
- the uniform emulsion nitrogen gas is pressurized and filtered through a microporous filter filter of ⁇ 3 ⁇ m, sterilized by nitrogen filling, and cooled.
- coix seed oil contains the following ingredients:
- Preparation of glue Weigh the appropriate amount of gelatin, purified water, glycerin and 10% hydroxyethyl ester solution according to the weight ratio of 1:1.2:0.8:0.01; add glycerin, purified water and 10% hydroxyethyl ester solution to the rubber In the tank, after heating to 70 ° C, add gelatin and stir constantly, vacuum until the gelatin is completely dissolved, filter the glue, store at 59 ° C, and set aside;
- Preparation of liquid medicine Add the formula amount of coix seed oil and vitamin E into the ingredient tank, and stir constantly until it is evenly mixed;
- Pressure capsule select the appropriate pellet mold according to the size of the capsule, dry it at 16 °C and relative humidity ⁇ 35%, then remove the size pellets, then wash the pellets with 95% medicinal ethanol, and continue to dry until The amount of water is less than 12%, and the unqualified capsules are removed by visual inspection.
- coix seed oil contains the following ingredients:
- 1,3-dioleic acid-2-linoleic acid glyceride 18.50%
- Preparation of glue Weigh the appropriate amount of gelatin, purified water, glycerin and benzoic acid at a weight ratio of 1:1.2:0.8:0.01; add glycerin, purified water and benzoic acid to the gelatin tank in turn, heat to 90 °C, then Add gelatin and stir constantly, vacuum until the gelatin is completely dissolved, filter the glue, store at 60 ° C, and set aside;
- Preparation of liquid medicine Add the formula amount of coix seed oil and Tween 80 into the ingredient tank, and stir constantly until it is evenly mixed;
- Pressure capsule Select the appropriate pellet mold according to the size of the capsule, and then dry it at 26 ° C and relative humidity ⁇ 35%, then remove the size pellets, and then wash the pellets with 95% medicinal ethanol, then continue to dry to contain The amount of water is less than 12%, and the unqualified capsules are removed by visual inspection.
- coix seed oil contains the following ingredients:
- Preparation of glue Weigh the appropriate amount of gelatin, purified water, glycerin and potassium sorbate according to the weight ratio of 1:0.9:0.6:0.005; add glycerin, purified water and potassium sorbate to the gelatin tank in turn, and heat to 80 °C. Then add gelatin and stir constantly, vacuum, until the gelatin is completely dissolved, filter the glue, store at 62 ° C, and set aside;
- Preparation of liquid medicine Add the formula amount of coix seed oil and vitamin E into the ingredient tank, and stir constantly until it is evenly mixed;
- Capsule Select the appropriate pellets according to the size of the capsules, and then dry at 20 °C and relative humidity ⁇ 35%, then remove the pellets, then wash the pellets with 95% medicinal ethanol, and continue to dry until The amount of water is less than 12%, and the unqualified capsules are removed by visual inspection.
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Abstract
Description
位置 | 化学位移 | H数目、峰形及耦合常数 |
H-C=C | 5.34 | 2H,m |
CH-OCO | 5.26 | 1H,m |
-CH2-OCO | 4.29 | 2H,dd,12.0,4.4 |
-CH2-OCO | 4.14 | 2H,d,12.0,6.0 |
-CH2COO | 2.31 | 2H,t,7.6 |
-CH2COO | 2.31 | 4H,t,7.6 |
-CH2-CH= | 2.00 | 4H,m |
-CH2CH2COO | 1.60 | 6H,m |
-CH2 | 1.27 | 68H,m |
-CH3 | 0.87 | 9H,t,6.8 |
位置 | 化学位移 | 位置 | 化学位移 |
C1 1 | 173.282 | C10 1 | 29.750~29.040 |
2 | 172.839 | 2 | 129.999 |
3 | 173.282 | 3 | 29.750~29.040 |
C2 1 | 34.026 | C11 1 | 29.750~29.040 |
2 | 34.179 | 2 | 27.205 |
3 | 34.026 | 3 | 29.750~29.040 |
C3 1 | 24.848 | C12 1 | 29.750~29.040 |
2 | 24.848 | 2 | 29.750~29.040 |
3 | 24.848 | 3 | 29.750~29.040 |
C4 1 | 29.750~29.040 | C13 1 | 29.750~29.040 |
2 | 29.750~29.040 | 2 | 29.750~29.040 |
3 | 29.750~29.040 | 3 | 29.750~29.040 |
C5 1 | 29.750~29.040 | C14 1 | 31.895 |
2 | 29.750~29.040 | 2 | 29.750~29.040 |
3 | 29.750~29.040 | 3 | 31.895 |
C6 1 | 29.750~29.040 | C15 1 | 22.672 |
2 | 29.750~29.040 | 2 | 29.750~29.040 |
3 | 29.750~29.040 | 3 | 22.672 |
C7 1 | 29.750~29.040 | C16 1 | 14.099 |
2 | 29.750~29.040 | 2 | 31.895 |
3 | 29.750~29.040 | 3 | 14.099 |
C8 1 | 29.750~29.040 | C17 2 | 22.672 |
2 | 27.159 | C18 2 | 14.099 |
3 | 29.750~29.040 | CHO | 68.852 |
C9 1 | 29.750~29.040 | CH2O | 62.076 |
2 | 129.687 | ||
3 | 29.750~29.040 |
位置 | 化学位移 | H数目、峰形及耦合常数 |
H-C=C | 5.35 | 4H,m |
β-CH-OCO | 5.26 | 1H,m |
α-CH2-OCO | 4.29 | 2H,dd,11.6,4.0 |
α-CH2-OCO | 4.14 | 2H,d,12.0,6.0 |
-CH2COO | 2.31 | 2H,t,7.6 |
-CH2COO | 2.31 | 4H,t,7.6 |
-CH2-CH= | 2.01 | 8H,m |
-CH2CH2COO | 1.60 | 6H,m |
-CH2 | 1.27 | 74H,m |
-CH3 | 0.87 | 9H,t,6.8 |
位置 | 化学位移 | 位置 | 化学位移 |
C1 1 | 173.258 | C10 1 | 129.999 |
2 | 172.839 | 2 | 129.999 |
3 | 173.282 | 3 | 29.00~30.00 |
C2 1 | 34.028 | C11 1 | 27.206 |
2 | 34.179 | 2 | 27.206 |
3 | 34.028 | 3 | 29.00~30.00 |
C3 1 | 24.848 | C12 1 | 29.00~30.00 |
2 | 24.848 | 2 | 29.00~30.00 |
3 | 24.848 | 3 | 29.00~30.00 |
C4 1 | 30.00~29.00 | C13 1 | 29.00~30.00 |
2 | 30.00~29.00 | 2 | 29.00~30.00 |
3 | 30.00~29.00 | 3 | 29.00~30.00 |
C5 1 | 30.00~29.00 | C14 1 | 29.00~30.00 |
2 | 30.00~29.00 | 2 | 29.00~30.00 |
3 | 30.00~29.00 | 3 | 31.895 |
C6 1 | 30.00~29.00 | C15 1 | 29.00~30.00 |
2 | 30.00~29.00 | 2 | 29.00~30.00 |
3 | 30.00~29.00 | 3 | 22.672 |
C7 1 | 30.00~29.00 | C16 1 | 31.895 |
2 | 30.00~29.00 | 2 | 31.895 |
3 | 30.00~29.00 | 3 | 31.895 |
C8 1 | 27.159 | C17 1 | 22.672 |
2 | 27.159 | 2 | 22.672 |
3 | 29.00~30.00 | 3 | 22.672 |
C9 1 | 129.687 | C18 1 | 14.099 |
2 | 129.669 | 2 | 14.099 |
3 | 29.00~30.00 | 3 | 14.099 |
β‐CHO- | 68.852 | ||
α‐CH2O- | 62.076 |
位置 | 化学位移 | 位置 | 化学位移 |
C1 1 | 173.25 | C10 1 | 129.97 |
2 | 172.83 | 2 | 128.08 |
3 | 173.25 | 3 | 29.04~29.76 |
C2 1 | 34.03 | C11 1 | 27.19 |
2 | 34.18 | 2 | 25.62 |
3 | 34.04 | 3 | 29.04~29.76 |
C3 1 | 24.86 | C12 1 | 29.04~29.76 |
2b | 24.86 | 2 | 127.88 |
3 | 24.86 | 3 | 29.04~29.76 |
C4 1 | 29.04~29.76 | C13 1 | 29.04~29.76 |
2b | 29.04~29.76 | 2 | 130.22 |
3 | 29.04~29.76 | 3 | 29.04~29.76 |
C5 1 | 29.04~29.76 | C14 1 | 31.89 |
2b | 29.04~29.76 | 2 | 29.04~29.76 |
3 | 29.04~29.76 | 3 | 31.89 |
C6 1 | 29.04~29.76 | C15 1 | 22.67 |
2b | 29.04~29.76 | 2b | 22.56 |
3 | 29.04~29.76 | 3 | 22.67 |
C7 1 | 29.04~29.76 | C16 1 | 31.91 |
2b | 29.04~29.76 | 2 | 31.52 |
3 | 29.04~29.76 | 3 | 31.89 |
C8 1 | 29.04~29.76 | C17 1 | 22.67 |
2 | 27.19 | 2 | 22.56 |
3 | 29.04~29.76 | 3 | 22.67 |
C9 1 | 129.70 | C18 1 | 14.09 |
2 | 130.01 | 2 | 14.05 |
3 | 29.04~29.76 | 3 | 14.09 |
CH-O | 68.89 | ||
2CH2-O | 62.08 |
Claims (10)
- 一种薏苡仁油,其特征在于:该薏苡仁油中含有如下质量百分含量的5种甘油二酯类成分和11种甘油三酯类成分:1,3-二油酸甘油酯0.40~0.58%、1-亚油酸-3-油酸甘油二酯0.91~1.31%、1,2-二油酸甘油酯0.24~0.35%、1-油酸-2-亚油酸甘油二酯0.66~0.95%、1,2-二亚油酸甘油酯0.33~0.47%、三亚油酸甘油酯4.87~6.99%、1-油酸-2,3-二亚油酸甘油酯13.00~18.69%、1-棕榈酸-2,3-二亚油酸甘油酯5.25~7.54%、1,3-二油酸-2-亚油酸甘油酯13.23~19.02%、1-棕榈酸-2-亚油酸-3-油酸甘油酯10.26~14.75%、1,3-二棕榈酸-2-亚油酸甘油三酯2.28~3.28%、三油酸甘油酯14.44~20.76%、1-棕榈酸-2,3-二油酸甘油酯8.06~11.58%、1-油酸-2-亚油酸-3-硬脂酸甘油酯1.37~1.97%、1,3-二棕榈酸-2-油酸甘油酯1.52~2.19%和1,2-二油酸-3-硬脂酸甘油酯1.29~1.86%。
- 根据权利要求1所述的薏苡仁油,其特征在于:所述薏苡仁油按脂肪油检测理化常数为:20℃时相对密度0.916~0.920,20℃时折光率1.471~1.474,酸值<0.2,碘值100~106,皂化值186~195;所述甘油二酯成分和甘油三酯成分的质量百分含量为:1,3-二油酸甘油酯0.45~0.55%、1-亚油酸-3-油酸甘油二酯1.03~1.25%、1,2-二油酸甘油酯0.27~0.33%、1-油酸-2-亚油酸甘油二酯0.75~0.91%、1,2-二亚油酸甘油酯0.37~0.45%、三亚油酸甘油酯5.47~6.69%、1-油酸-2,3-二亚油酸甘油酯14.63~17.88%、1-棕榈酸-2,3-二亚油酸甘油酯5.9~7.21%、1,3-二油酸-2-亚油酸甘油酯14.88~18.19%、1-棕榈酸-2-亚油酸-3-油酸甘油酯11.55~14.11%、1,3-二棕榈酸-2-亚油酸甘油三酯2.57~3.14%、三油酸甘油酯16.25~19.86%、1-棕榈酸-2,3-二油酸甘油酯9.07~11.08%、1-油酸-2-亚油酸-3-硬脂酸甘油酯1.54~1.88%、1,3-二棕榈酸-2-油酸甘油酯1.71~2.09%和1,2-二油酸-3-硬脂酸甘油酯1.45~1.78%;优选地,所述甘油二酯成分和甘油三酯成分的质量百分含量为:1,3-二油酸甘油酯0.49~0.51%、1-亚油酸-3-油酸甘油二酯1.12~1.16%、1,2-二油酸甘油酯0.29~0.31%、1-油酸-2-亚油酸甘油二酯0.81~0.85%、1,2-二亚油酸甘油酯0.40~0.42%、三亚油酸甘油酯5.96~6.20%、1-油酸-2,3-二亚油酸甘油酯15.93~16.58%、1-棕榈酸-2,3-二亚油酸甘油酯6.43~6.69%、1,3-二油酸-2-亚油酸甘油酯16.20~16.87%、1-棕榈酸-2-亚油酸-3-油酸甘油酯12.57~13.09%、1,3-二棕榈酸-2-亚油酸甘油三酯2.79~2.91%、三油酸甘油酯17.69~18.42%、1-棕榈酸-2,3-二油酸甘油酯9.87~10.27%、1-油酸-2-亚油酸-3-硬脂酸甘油酯1.68~1.74%、1,3-二棕榈酸-2-油酸甘油酯1.86~1.94%和1,2-二油酸-3-硬脂酸甘油酯1.58~1.65%。
- 一种权利要求1所述薏苡仁油的制备方法,具体包括如下步骤:超临界二氧化碳萃取:取薏苡仁粉碎成20目~100目,采用600L×2超临界CO2萃取器萃取,将薏苡仁粉装入萃取釜,用夹套循环热水加热CO2预热器、萃取釜和分离柱,使萃取温度和分离温度分别达到33~45℃和30~45℃,保持一级解析釜和二级解析釜出口温度分别为20~50℃和15~35℃;液态CO2以1~3t/h的流量经高压泵加压进入CO2预热器,成为超临界状态下的流体,进入萃取釜,保持压力19~23Mpa,萃取薏苡仁油;溶有薏苡仁油的CO2流体进入分离柱,控制分离柱压力7~10Mpa,分离得到薏苡仁油;从分离柱出来的CO2气体先后进入一级、二级解析釜,分别保持压力为5~7Mpa和4~6Mpa,弃去解析得到的水分等杂质,CO2气体经冷凝器变成液态CO2,循环使用,连续萃取2~3h,得到薏苡仁油;精制:取超临界CO2萃取得到的薏苡仁油,加入油重量65%的60℃~90℃石油醚,再根据酸值,加入油重36%~56%的2%NaOH溶液,搅拌10min后,静置18~24h后,除去下层皂脚,取上层用纯化水进行水洗,静置18~24h后,除去下层废水;取上层进行第二次水洗,静置40~50h后,除去下层废水;取上层加油重70%~90%丙酮破乳,静置2~4h后,除去下层废丙酮; 取上层油溶液,加入3%~8%的经活化的中性氧化铝,搅拌30min后,过滤;滤液加热后,加入2%~6%经活化的混合吸附剂,搅拌,在40~50℃下保温30min,过滤;滤液减压回收溶剂后,再加纯化水进行水洗,静置1~2h后,除去下层废水;上层油在充氮条件下,加热减压浓缩,再经160~170℃减压干热灭菌1~2h,冷却后经0.2μm微孔滤膜过滤,分装于500ml玻璃输液瓶中,充氮,密封,即得;优选地,所述精制步骤如下:取超临界CO2萃取得到的薏苡仁油,加入油重量65%的60℃~90℃石油醚,再根据酸值,加入油重36%~56%的2%NaOH溶液,搅拌10min后,静置20h后,除去下层皂脚,取上层用纯化水进行水洗,静置22h后,除去下层废水;取上层进行第二次水洗,静置46h后,除去下层废水;取上层加油重70%~90%丙酮破乳,静置3h后,除去下层废丙酮;取上层油溶液,加入5%的经活化的中性氧化铝,搅拌30min后,过滤;滤液加热后,加入4%经活化的高岭土:活性炭=1:1的混合吸附剂,搅拌,在40~50℃下保温30min,过滤;滤液减压回收溶剂后,再加纯化水进行水洗,静置1h后,除去下层废水;上层油在充氮条件下,加热减压浓缩,再经160~170℃减压干热灭菌2h,冷却后经0.2μm微孔滤膜过滤,分装于500ml玻璃输液瓶中,充氮,密封,即得。
- 一种药物制剂,其特征在于含有治疗有效量的权利要求1~3任一所述的薏苡仁油及一种或几种药学上可接受的载体,其中所述药学上可接受的载体包括药学领域常规的稀释剂、赋形剂、填充剂、乳化剂、粘合剂、润滑剂、吸收促进剂、表面活性剂、崩解剂、润滑剂或抗氧化剂,必要时还可以加入香味剂、甜味剂、防腐剂或着色剂;其中,所述药学上可接受的载体可以选自:甘露醇、山梨醇、焦亚硫酸钠、亚硫酸氢钠、硫代硫酸钠、盐酸半胱氨酸、巯基乙酸、蛋氨酸、大豆磷脂、维生素C、维生素E、EDTA二钠、EDTA钙钠,一价碱金属的碳酸盐、醋酸盐、磷酸盐或其水溶液、盐酸、醋酸、硫酸、磷酸、氨基酸、氯化钠、氯化钾、乳酸钠、羟苯乙酯溶液、苯甲酸、山梨酸钾、醋酸氯己定、木糖醇、麦芽糖、葡萄糖、果糖、右旋糖苷、甘氨酸、淀粉、蔗糖、乳糖、甘露糖醇、硅衍生物、纤维素及其衍生物、藻酸盐、明胶、聚乙烯吡咯烷酮、甘油、土温80、琼脂、碳酸钙、碳酸氢钙、表面活性剂、聚乙二醇、环糊精、β-环糊精、磷脂类材料、高岭土、滑石粉、硬脂酸钙或硬脂酸镁。
- 根据权利要求4所述药物制剂,其可以是口服固体制剂、口服液体制剂或注射剂;其中,所述口服固体制剂选自胶囊剂、片剂、滴丸、颗粒剂、浓缩丸中的任何一种;所述口服液体制剂选自水性或油性悬浮液、溶液、乳剂、糖浆剂或酏剂,或是一种在使用前可用水或其它适宜的载体复配的干燥产品;所述注射剂选自纳米混悬剂、脂质体、乳剂、冻干粉针剂和水针剂中的任何一种。
- 根据权利要求5所述药物制剂,其特征在于所述注射剂包含如下成分:薏苡仁油 50~350g注射用大豆磷脂或可供注射用大豆磷脂 10~40g注射用甘油或可供注射用甘油 15~50g注射用水加至 1000ml。
- 根据权利要求6所述药物制剂的制备方法,其特征在于包括如下步骤:称取处方配制量的注射用大豆磷脂或可供注射用大豆磷脂,加适量的注射用水后,用高剪切分散乳化机分散至无块状及颗粒状固体,加入按配方量称取的注射用甘油或可供注射用 甘油,并加注射用水至规定量,搅拌均匀备用;另称取薏苡仁油,将称取的油酯与水相分别加热至60~70℃后,置高压均质机进行高压乳化,乳化时均质机低压为5~12MPa,高压为25~50MPa,再循环均质3~6遍,至2μm以下颗粒应不少于95%,5μm以上颗粒不得检出,必要时用NaOH或HCl调节pH至4.8~8.5,优选6.8~7,最优选为6.8;将制得均匀乳剂氮气加压通过小于等于3μm的微孔滤芯过滤器过滤,充氮灌装灭菌,冷却即得。
- 根据权利要求5所述药物制剂,其特征在于所述胶囊剂包含如下成分:薏苡仁油 200~800g抗氧化剂和/或乳化剂 0.20~0.60g制成 1000粒。
- 根据权利要求8所述药物制剂的制备方法,其特征在于包括如下步骤:胶液配制:按重量比为1∶0.6~1.2∶0.3~0.8∶0.0001~0.01称取适量明胶、纯化水、甘油和防腐剂;依次将甘油、纯化水、防腐剂加入化胶罐内,加热至70℃~90℃后,再加入明胶不断搅拌、抽真空,直至明胶完全溶解,将胶液过滤,在56~62℃下存放,备用;药液配制:将配方量的薏苡仁油、抗氧化剂和/或乳化剂加入配料罐内,不断搅拌,直至混合均匀;压胶囊:根据胶囊大小选择合适的压丸模具,在15~30℃、相对湿度小于35%条件下进行压丸定型后干燥,剔除大小丸,再用95%药用乙醇洗丸后,继续干燥至含水量小于12%,目检剔除不合格胶囊,包装即得;其中,所述防腐剂选自10%羟苯乙酯溶液、苯甲酸、山梨酸钾和醋酸氯己定中的一种;所述抗氧化剂为维生素E,乳化剂为吐温80。
- 根据权利要求1所述薏苡仁油在制备抗肿瘤药物中的应用:其中,所述肿瘤是指早期、中期或晚期的肺癌、肝癌、胰腺癌、前列腺癌、卵巢癌或乳腺癌。
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Citations (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN1080176A (zh) * | 1993-01-01 | 1994-01-05 | 浙江省中医院 | 薏苡仁中性油脂乳剂 |
CN1485418A (zh) * | 2002-09-28 | 2004-03-31 | 李大鹏 | 超临界二氧化碳提取薏苡仁粗油方法 |
CN1485072A (zh) * | 2002-09-28 | 2004-03-31 | 治疗前列腺疾病的薏苡仁油软胶囊及其应用 | |
CN104173824A (zh) * | 2014-07-18 | 2014-12-03 | 浙江康莱特集团有限公司 | 含有8种甘油三酯的薏苡仁油、制剂及其应用 |
US20140370129A1 (en) * | 2013-06-14 | 2014-12-18 | Zhejiang Kanglaite Group Co., Ltd. | Dosing regimen and method for treating cancer using a coix seed oil emulsion |
Family Cites Families (8)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
PH30249A (en) * | 1992-09-16 | 1997-02-05 | Zhejiang Provincial Hospital O | Neutral lipids from endosperm of job's tears |
CN1029662C (zh) * | 1992-09-17 | 1995-09-06 | 李大鹏 | 薏苡仁中性油脂及其提取方法 |
JP2002212586A (ja) * | 2001-01-19 | 2002-07-31 | Kanegafuchi Chem Ind Co Ltd | 油脂の精製方法 |
CN1234828C (zh) * | 2002-11-21 | 2006-01-04 | 上海高科联合生物技术研发有限公司 | 超临界二氧化碳萃取薏苡仁油的方法 |
CN1778380A (zh) * | 2004-11-23 | 2006-05-31 | 乔志亚生技股份有限公司 | 薏仁油萃取的方法及组成分及其疗效 |
CN101036761B (zh) * | 2007-04-23 | 2010-05-19 | 肖志勇 | 一种薏苡仁油的制备方法 |
CN101940738A (zh) * | 2010-07-27 | 2011-01-12 | 辽宁中医药大学 | 薏苡仁抗癌中药及其制备方法 |
CN102177978B (zh) * | 2011-04-14 | 2013-01-30 | 西南大学 | 薏苡仁米糠及其运用 |
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Patent Citations (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN1080176A (zh) * | 1993-01-01 | 1994-01-05 | 浙江省中医院 | 薏苡仁中性油脂乳剂 |
CN1485418A (zh) * | 2002-09-28 | 2004-03-31 | 李大鹏 | 超临界二氧化碳提取薏苡仁粗油方法 |
CN1485072A (zh) * | 2002-09-28 | 2004-03-31 | 治疗前列腺疾病的薏苡仁油软胶囊及其应用 | |
US20140370129A1 (en) * | 2013-06-14 | 2014-12-18 | Zhejiang Kanglaite Group Co., Ltd. | Dosing regimen and method for treating cancer using a coix seed oil emulsion |
CN104173824A (zh) * | 2014-07-18 | 2014-12-03 | 浙江康莱特集团有限公司 | 含有8种甘油三酯的薏苡仁油、制剂及其应用 |
Non-Patent Citations (2)
Title |
---|
See also references of EP3170497A4 * |
XIANG, ZHIMIN ET AL.: "Identification of Triacylglycerols In Coix Oil by High Performance Liquid Chromatography-Atmospheric Pressure Chemicalionization-Mass Spectrometry", CHINA JOURNAL OF CHINESE MATERIA MEDICA, vol. 33, no. 18, 30 September 2005 (2005-09-30), pages 1436 - 1438, XP008183620 * |
Also Published As
Publication number | Publication date |
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CN106470680B (zh) | 2017-09-12 |
NZ726583A (en) | 2018-01-26 |
KR101919387B1 (ko) | 2018-11-16 |
AP2017009709A0 (en) | 2017-01-31 |
PL3170497T3 (pl) | 2020-02-28 |
EP3170497A4 (en) | 2018-03-07 |
EP3170497B1 (en) | 2019-09-04 |
EA033688B1 (ru) | 2019-11-15 |
AU2015291532B2 (en) | 2018-03-29 |
JP2017521497A (ja) | 2017-08-03 |
EP3170497A1 (en) | 2017-05-24 |
CA2954797A1 (en) | 2016-01-21 |
DK3170497T3 (da) | 2019-12-09 |
SG11201700124SA (en) | 2017-03-30 |
CN105311486A (zh) | 2016-02-10 |
CN107320469A (zh) | 2017-11-07 |
JP6473812B2 (ja) | 2019-02-20 |
CN106470680A (zh) | 2017-03-01 |
KR20170039129A (ko) | 2017-04-10 |
AU2015291532A1 (en) | 2016-12-08 |
CA2954797C (en) | 2019-10-29 |
EA201790120A1 (ru) | 2017-07-31 |
US10596218B2 (en) | 2020-03-24 |
US20170209518A1 (en) | 2017-07-27 |
CN107320469B (zh) | 2018-12-18 |
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