CN111171106A - Preparation method of 24-hydroxystearyl glycyrrhetinate - Google Patents
Preparation method of 24-hydroxystearyl glycyrrhetinate Download PDFInfo
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- CN111171106A CN111171106A CN202010101132.9A CN202010101132A CN111171106A CN 111171106 A CN111171106 A CN 111171106A CN 202010101132 A CN202010101132 A CN 202010101132A CN 111171106 A CN111171106 A CN 111171106A
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- Prior art keywords
- glycyrrhetinic acid
- hydroxystearyl
- solution
- hydroxy
- ester
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- MPDGHEJMBKOTSU-YKLVYJNSSA-N 18beta-glycyrrhetic acid Chemical compound C([C@H]1C2=CC(=O)[C@H]34)[C@@](C)(C(O)=O)CC[C@]1(C)CC[C@@]2(C)[C@]4(C)CC[C@@H]1[C@]3(C)CC[C@H](O)C1(C)C MPDGHEJMBKOTSU-YKLVYJNSSA-N 0.000 title claims abstract description 40
- 238000002360 preparation method Methods 0.000 title claims abstract description 19
- 229960003720 enoxolone Drugs 0.000 claims abstract description 38
- LPLVUJXQOOQHMX-QWBHMCJMSA-N glycyrrhizinic acid Chemical compound O([C@@H]1[C@@H](O)[C@H](O)[C@H](O[C@@H]1O[C@@H]1C([C@H]2[C@]([C@@H]3[C@@]([C@@]4(CC[C@@]5(C)CC[C@@](C)(C[C@H]5C4=CC3=O)C(O)=O)C)(C)CC2)(C)CC1)(C)C)C(O)=O)[C@@H]1O[C@H](C(O)=O)[C@@H](O)[C@H](O)[C@H]1O LPLVUJXQOOQHMX-QWBHMCJMSA-N 0.000 claims abstract description 21
- 229960004949 glycyrrhizic acid Drugs 0.000 claims abstract description 19
- 239000000126 substance Substances 0.000 claims abstract description 18
- 239000004378 Glycyrrhizin Substances 0.000 claims abstract description 17
- LPLVUJXQOOQHMX-UHFFFAOYSA-N glycyrrhetinic acid glycoside Natural products C1CC(C2C(C3(CCC4(C)CCC(C)(CC4C3=CC2=O)C(O)=O)C)(C)CC2)(C)C2C(C)(C)C1OC1OC(C(O)=O)C(O)C(O)C1OC1OC(C(O)=O)C(O)C(O)C1O LPLVUJXQOOQHMX-UHFFFAOYSA-N 0.000 claims abstract description 17
- UYRUBYNTXSDKQT-UHFFFAOYSA-N glycyrrhizic acid Natural products CC1(C)C(CCC2(C)C1CCC3(C)C2C(=O)C=C4C5CC(C)(CCC5(C)CCC34C)C(=O)O)OC6OC(C(O)C(O)C6OC7OC(O)C(O)C(O)C7C(=O)O)C(=O)O UYRUBYNTXSDKQT-UHFFFAOYSA-N 0.000 claims abstract description 17
- 235000019410 glycyrrhizin Nutrition 0.000 claims abstract description 17
- MPDGHEJMBKOTSU-UHFFFAOYSA-N Glycyrrhetinsaeure Natural products C12C(=O)C=C3C4CC(C)(C(O)=O)CCC4(C)CCC3(C)C1(C)CCC1C2(C)CCC(O)C1(C)C MPDGHEJMBKOTSU-UHFFFAOYSA-N 0.000 claims abstract description 16
- 238000000605 extraction Methods 0.000 claims abstract description 10
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 45
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 claims description 44
- 239000000243 solution Substances 0.000 claims description 43
- 239000007787 solid Substances 0.000 claims description 34
- 238000003756 stirring Methods 0.000 claims description 34
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 28
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 27
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 25
- 239000002904 solvent Substances 0.000 claims description 21
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims description 18
- 239000000706 filtrate Substances 0.000 claims description 18
- 238000001816 cooling Methods 0.000 claims description 16
- GLDOVTGHNKAZLK-UHFFFAOYSA-N octadecan-1-ol Chemical compound CCCCCCCCCCCCCCCCCCO GLDOVTGHNKAZLK-UHFFFAOYSA-N 0.000 claims description 16
- 239000000843 powder Substances 0.000 claims description 16
- 239000011347 resin Substances 0.000 claims description 16
- 229920005989 resin Polymers 0.000 claims description 16
- 238000005406 washing Methods 0.000 claims description 14
- 239000013078 crystal Substances 0.000 claims description 12
- 239000003480 eluent Substances 0.000 claims description 12
- 239000007921 spray Substances 0.000 claims description 12
- 238000001035 drying Methods 0.000 claims description 11
- 238000001914 filtration Methods 0.000 claims description 11
- 150000002148 esters Chemical class 0.000 claims description 10
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 9
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 claims description 8
- 239000007864 aqueous solution Substances 0.000 claims description 8
- 238000010438 heat treatment Methods 0.000 claims description 8
- GOQYKNQRPGWPLP-UHFFFAOYSA-N n-heptadecyl alcohol Natural products CCCCCCCCCCCCCCCCCO GOQYKNQRPGWPLP-UHFFFAOYSA-N 0.000 claims description 8
- 238000005507 spraying Methods 0.000 claims description 8
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 claims description 5
- 235000011114 ammonium hydroxide Nutrition 0.000 claims description 5
- 239000008367 deionised water Substances 0.000 claims description 5
- 229910021641 deionized water Inorganic materials 0.000 claims description 5
- 239000000203 mixture Substances 0.000 claims description 5
- 239000003208 petroleum Substances 0.000 claims description 5
- 238000000967 suction filtration Methods 0.000 claims description 5
- 238000010992 reflux Methods 0.000 claims description 4
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 claims description 3
- 239000012156 elution solvent Substances 0.000 claims description 2
- 238000011068 loading method Methods 0.000 claims description 2
- 238000000034 method Methods 0.000 claims 9
- 235000013305 food Nutrition 0.000 abstract description 4
- 239000002994 raw material Substances 0.000 abstract description 4
- 239000002537 cosmetic Substances 0.000 abstract description 3
- 239000003814 drug Substances 0.000 abstract description 3
- 230000003110 anti-inflammatory effect Effects 0.000 abstract description 2
- 239000004519 grease Substances 0.000 abstract description 2
- 238000010828 elution Methods 0.000 description 4
- 239000007788 liquid Substances 0.000 description 4
- 235000006200 Glycyrrhiza glabra Nutrition 0.000 description 3
- 244000303040 Glycyrrhiza glabra Species 0.000 description 3
- -1 glycyrrhetinic acid ester Chemical class 0.000 description 3
- 235000011477 liquorice Nutrition 0.000 description 3
- 239000000047 product Substances 0.000 description 3
- 238000005070 sampling Methods 0.000 description 3
- 108010011485 Aspartame Proteins 0.000 description 2
- 206010061218 Inflammation Diseases 0.000 description 2
- 239000000605 aspartame Substances 0.000 description 2
- IAOZJIPTCAWIRG-QWRGUYRKSA-N aspartame Chemical compound OC(=O)C[C@H](N)C(=O)N[C@H](C(=O)OC)CC1=CC=CC=C1 IAOZJIPTCAWIRG-QWRGUYRKSA-N 0.000 description 2
- 229960003438 aspartame Drugs 0.000 description 2
- 235000010357 aspartame Nutrition 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 239000001685 glycyrrhizic acid Substances 0.000 description 2
- 239000012535 impurity Substances 0.000 description 2
- 230000004054 inflammatory process Effects 0.000 description 2
- 150000002632 lipids Chemical class 0.000 description 2
- 238000000926 separation method Methods 0.000 description 2
- 239000006228 supernatant Substances 0.000 description 2
- 206010042496 Sunburn Diseases 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 230000003467 diminishing effect Effects 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 230000002708 enhancing effect Effects 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 230000036039 immunity Effects 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000001766 physiological effect Effects 0.000 description 1
- 230000004952 protein activity Effects 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 230000002195 synergetic effect Effects 0.000 description 1
- 239000013076 target substance Substances 0.000 description 1
- 230000002087 whitening effect Effects 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J63/00—Steroids in which the cyclopenta(a)hydrophenanthrene skeleton has been modified by expansion of only one ring by one or two atoms
- C07J63/008—Expansion of ring D by one atom, e.g. D homo steroids
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
- A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
- A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
- A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
- A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
- A23L33/115—Fatty acids or derivatives thereof; Fats or oils
- A23L33/12—Fatty acids or derivatives thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
- A61K8/63—Steroids; Derivatives thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
- A61Q19/00—Preparations for care of the skin
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
- A23V2002/00—Food compositions, function of food ingredients or processes for food or foodstuffs
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Food Science & Technology (AREA)
- Polymers & Plastics (AREA)
- Nutrition Science (AREA)
- Engineering & Computer Science (AREA)
- Mycology (AREA)
- Rheumatology (AREA)
- Medicinal Chemistry (AREA)
- Epidemiology (AREA)
- Pain & Pain Management (AREA)
- Oil, Petroleum & Natural Gas (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Birds (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Dermatology (AREA)
- Pharmacology & Pharmacy (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Saccharide Compounds (AREA)
- Cosmetics (AREA)
Abstract
A24-hydroxy stearyl alcohol glycyrrhetinic acid ester preparation method, relate to the food, cosmetic, medicine, health-care product field, the invention regards glycyrrhizin as raw materials, the extraction process is simple, the operability is strong; the yield of effective substances is high, and resources are fully utilized; compared with 24-hydroxy-glycyrrhetinic acid, the prepared 24-hydroxy-stearyl glycyrrhetinic acid ester has obviously changed solubility in grease due to introduction of lipophilic higher alkanol, has better anti-inflammatory effect compared with 24-hydroxy-glycyrrhetinic acid, and is suitable for wide popularization and application.
Description
Technical Field
The invention relates to the field of food cosmetics, in particular to a preparation method of 24-hydroxystearyl glycyrrhetinic acid ester.
Background
The 24-hydroxy-glycyrrhetinic acid is known to be a metabolite of glycyrrhizic acid in vivo, has the functions of resisting inflammation, preserving moisture, whitening and preventing sunburn, but the 24-hydroxy-glycyrrhetinic acid has poor lipid solubility and has some disadvantages in application. The higher alkanol substances have certain physiological activity, such as the effects of reducing blood fat, improving protein activity, enhancing immunity, diminishing inflammation and the like, related products are widely used in the industries of food, medicines, health care products and the like, and meanwhile, the solubility of the 24-hydroxy-stearyl glycyrrhetinic ester in the oil ester is increased due to the introduction of the higher alkanol, so that the application is more convenient, and meanwhile, the synergistic effect exists, the product effect is improved, and the application prospect is good.
The inventor has not found reports related to or similar to the invention in published documents and patent searches.
Therefore, how to provide a preparation method of 24-hydroxystearyl glycyrrhetinate becomes a long-term technical demand of the technical personnel in the field.
Disclosure of Invention
In order to overcome the defects in the background technology, the invention provides a preparation method of 24-hydroxystearyl glycyrrhetinic acid ester, which takes glycyrrhizin as a raw material, has the characteristics of simple extraction process, strong operability and the like, has high yield of effective substances, fully utilizes resources and the like.
In order to achieve the above purpose, the invention adopts the following technical scheme:
a preparation method of 24-hydroxystearyl glycyrrhetinate specifically comprises the following steps:
firstly, putting glycyrrhizin into stirring equipment, then adding a proper amount of solvent into the stirring equipment, stirring and extracting for 1-2 hours at normal temperature, wherein the ratio of glycyrrhizin to solvent is 1: 8-1: 10, closing the stirring equipment after extraction is finished, filtering the mixture to remove insoluble substances, retaining filtrate, repeating the steps to extract the glycyrrhizin at least twice, combining the extracting solutions, and concentrating the extracting solution at 60-70 ℃ under reduced pressure to form thick paste;
secondly, adding water with the weight being 4-8 times that of the concentrated thick paste obtained in the previous step, adding ammonia water to dissolve the thick paste to obtain a solution, sequentially extracting the solution with acetone, diethyl ether and petroleum ether in a ratio of 1:1 for 2-3 times, repeatedly extracting each solvent for 2-3 times, concentrating the extracted water phase at 50-70 ℃ under reduced pressure until the solid content is 30-50%, and spraying at 120-140 ℃ to obtain spray powder;
thirdly, adding water into the spray powder obtained in the second step to prepare a 3-5% solution, purifying the solution by using macroporous resin, washing the solution by using 2-8 column volumes of water after the sample loading is finished, eluting the solution by using 30-80% ethanol or methanol as an eluent after the washing to obtain an eluent, and concentrating the eluent to a thick paste under reduced pressure at 50-70 ℃;
fourthly, adding the concentrated thick paste obtained in the third step into sulfuric acid aqueous solution with the weight 6-10 times of that of the concentrated thick paste, stirring and reacting at the temperature of 70-100 ℃ until the reaction is complete, cooling after the reaction is complete, separating out because 24-hydroxy-glycyrrhetinic acid is insoluble in water, cooling to room temperature, performing suction filtration, washing with deionized water until the pH value is unchanged, drying the solid at the temperature of 40-60 ℃, and obtaining the solid which is 24-hydroxy-glycyrrhetinic acid after drying;
fifthly, feeding the 24-hydroxy-glycyrrhetinic acid and stearyl alcohol obtained in the fourth step in proportion, adding water for dissolving, adding sulfuric acid, wherein the amount of the sulfuric acid is 8-12 times of the total amount of dry matters, the amount of the sulfuric acid is 3% -7% of the amount of the dry matters, heating to 90-100 ℃, heating for reflux for 2-4 hours, and collecting solid matters after cooling;
and sixthly, dissolving the solid matter obtained in the fifth step by 8-12 times of high-concentration ethanol at 70-90 ℃, cooling, crystallizing, filtering, dividing into a solution and a crystal, and drying the crystal to obtain the 24-hydroxy-stearyl glycyrrhetinic acid ester.
In the preparation method of 24-hydroxystearyl glycyrrhetinate, the solvent in the first step is one or the combination of two or more of ethyl acetate, n-butanol or propanol.
In the preparation method of 24-hydroxystearyl glycyrrhetinate, the solvent in the first step is preferably ethyl acetate.
In the preparation method of 24-hydroxystearyl glycyrrhetinate, the ratio of glycyrrhizin to solvent in the first step is preferably 1: 8.
In the preparation method of 24-hydroxystearyl glycyrrhetinate, the pH value of the solution in the second step is 7.5-9.
In the preparation method of 24-hydroxystearyl glycyrrhetinate, the type of the macroporous resin in the third step is any one of HPD-400, HPD-500, HPD-600, D101 and D1300.
In the preparation method of 24-hydroxystearyl glycyrrhetinate, the type of the macroporous resin in the third step is preferably D101 type resin.
In the preparation method of 24-hydroxystearyl glycyrrhetinate, the preferred eluting solvent is ethanol during elution in the third step.
In the preparation method of 24-hydroxystearyl glycyrrhetinate, the sulfuric acid concentration of the sulfuric acid aqueous solution in the fourth step is 6-8%.
In the preparation method of 24-hydroxystearyl glycyrrhetinate, the feeding ratio of 24-hydroxy-glycyrrhetinic acid to stearyl alcohol in the fifth step is 1: 1.
By adopting the technical scheme, the invention has the following advantages:
the liquorice aspartame is used as the raw material, the extraction process is simple, and the operability is strong; the yield of effective substances is high, and resources are fully utilized; compared with 24-hydroxy-glycyrrhetinic acid, the prepared 24-hydroxy-stearyl glycyrrhetinic acid ester has obviously changed solubility in grease due to introduction of lipophilic higher alkanol, has better anti-inflammatory effect compared with 24-hydroxy-glycyrrhetinic acid, and is suitable for wide popularization and application.
Detailed Description
The present invention will be explained in more detail by the following examples, which are not intended to limit the invention;
the preparation method of 24-hydroxystearyl glycyrrhetinate provided by the invention specifically comprises the following steps:
firstly, putting the glycyrrhizin into stirring equipment, wherein the stirring equipment is the existing mature equipment, has more types and is not the content protected by the invention, so the concrete structure of the glycyrrhizin is not described in detail; and then adding a proper amount of solvent into stirring equipment, stirring and extracting for 1-2 hours at normal temperature, wherein the material-liquid ratio of the glycyrrhizin to the solvent is 1: 8-1: 10, wherein in specific implementation, the material-liquid ratio of the glycyrrhizin to the solvent is preferably 1:8, the solvent is one or a combination of two or more of ethyl acetate, n-butanol or propanol, and the solvent is preferably ethyl acetate; after extraction is finished, the stirring equipment is closed, the mixture is filtered to remove insoluble substances, filtrate is reserved, the steps are repeated to extract the glycyrrhizin at least twice, the extracting solutions are combined, and the extracting solution is concentrated under reduced pressure at 60-70 ℃ to form thick paste;
secondly, adding water 4-8 times the weight of the concentrated thick paste obtained in the previous step into the concentrated thick paste, adding water 6 times the weight of the concentrated thick paste into the concentrated thick paste as a preferred scheme during specific implementation, adding ammonia water to dissolve the concentrated thick paste to obtain a solution, wherein the pH value of the solution is 7.5-9, extracting the solution by using acetone, diethyl ether and petroleum ether 1:1 in sequence, repeatedly extracting each solvent for 2-3 times, concentrating the extracted water phase at 50-70 ℃ under reduced pressure to obtain 30-50% of solid content, spraying at 120-140 ℃ to obtain spraying powder, and concentrating the extracted water phase at 60 ℃ under reduced pressure to obtain 40% of solid content during specific implementation, and spraying at 130 ℃ to obtain spraying powder as a preferred scheme;
thirdly, adding water into the spray powder obtained in the second step to prepare a 3-5% solution, wherein in specific implementation, the spray powder is added with water to prepare a 4% solution as a preferred scheme, the solution macroporous resin is purified, the type of the macroporous resin is HPD-400 or HPD-500 or HPD-600 or D101 or D1300, the type of the macroporous resin is preferably D101 type resin, the volume of the macroporous resin is 3-10 times of the feeding amount, the sampling speed is 1-2BV/h, in specific implementation, the volume of the macroporous resin is 8 times of the feeding amount, the sampling speed is 1.5BV/h as the preferred scheme, after sampling is completed, washing is performed by using 2-8 column volumes of water, in specific implementation, washing is performed by using 3 column volumes of water as the preferred scheme, after water washing, eluting is performed by using 30-80% ethanol or methanol as an eluent to obtain eluent, preferably, the elution solvent is ethanol during elution, the elution solution is concentrated into thick paste under reduced pressure at 50-70 ℃, and the elution solution is concentrated into thick paste under reduced pressure at 60 ℃ during specific implementation as a preferred scheme;
fourthly, adding a sulfuric acid aqueous solution which is 6-10 times of the weight of the concentrated thick paste obtained in the third step into the concentrated thick paste, wherein the sulfuric acid concentration of the sulfuric acid aqueous solution is 6% -8% during implementation, stirring and reacting for 4-8 hours at 70-100 ℃ until the reaction is complete, cooling after the reaction is complete, and preferably, the reaction time is 6-8 hours during implementation, at the moment, because 24-hydroxy-glycyrrhetinic acid is insoluble in water, the concentrated thick paste can be separated out, cooling to room temperature, carrying out suction filtration, washing with deionized water until the pH value is unchanged, drying the solid at 40-60 ℃, wherein the dried solid is 24-hydroxy-glycyrrhetinic acid, and drying the solid at 50 ℃ is taken as a preferred scheme during implementation;
fifthly, feeding the 24-hydroxy-glycyrrhetinic acid and stearyl alcohol obtained in the fourth step according to a proportion, wherein the feeding proportion of the 24-hydroxy-glycyrrhetinic acid and the stearyl alcohol in the fifth step is 1:1, adding water for dissolving, the amount of water is 8-12 times of the total amount of dry matters, adding sulfuric acid, the amount of sulfuric acid is 3% -7% of the total amount of dry matters, heating to 90-100 ℃, heating and refluxing for 2-4 hours, cooling and collecting solid matters, wherein in the implementation, the amount of water is 10 times of the total amount of dry matters, the amount of sulfuric acid is 5% of the total amount of dry matters, heating to 100 ℃, and heating and refluxing for 3 hours are a preferred scheme;
and sixthly, dissolving 8-12 times of the solid substance obtained in the fifth step by using ethanol with high concentration of 70-90 ℃, cooling and crystallizing, filtering and dividing into a solution and a crystal, drying the crystal to obtain the 24-hydroxy-stearyl glycyrrhetinate, and during implementation, dissolving the solid substance by using ethanol with high concentration of 10 times and 80 ℃ is the preferred scheme.
The specific embodiment of the invention is as follows:
example 1:
step one, 5kg of glycyrrhizin is taken and extracted by 50L of ethyl acetate, stirring extraction is carried out for 1 hour, stirring is turned off after 1 hour, about 2.03kg of insoluble substances are removed by filtration, filtrate is marked as filtrate 1, the insoluble substances are extracted by 500L of ethyl acetate again, stirring extraction is carried out for 1 hour, stirring is turned off after one hour, about 1.88kg of insoluble substances are removed by filtration, the filtrate is filtrate 2, and the filtrate 1 and the filtrate 2 are combined to form filtrate 3;
secondly, concentrating the extract of the filtrate 3 to 8L at 65 ℃, adding 19L of water into the concentrated solution, adding ammonia water, stirring for dissolving, measuring the pH value of the solution to 8.5 after dissolving, adding 19L of acetone into the solution, stirring for 20min, standing for liquid separation, recovering an acetone phase, extracting the water phase with 19L of acetone again, extracting the water phase with diethyl ether and petroleum ether in sequence after extraction, extracting each solvent twice, concentrating the extracted water phase at 60 ℃ under reduced pressure until the solid content is 40%, and spraying at 130 ℃ to obtain 1.10kg of spray powder;
thirdly, adding 27.5L of water into the spray powder obtained in the second step, stirring until the spray powder is dissolved, separating the solution by using D101 type macroporous resin, wherein the volume of a column is 8L, after the column is loaded, washing 24L of water to remove impurities with large polarity, eluting by using 40L of 30% ethanol until no 24-hydroxy-glycyrrhizic acid exists, collecting eluent, and concentrating the eluent under reduced pressure to 2L;
step four, adding 6.4L of prepared sulfuric acid aqueous solution with the concentration of 8% into the concentrated solution obtained in the step four, stirring and reacting for 8 hours at the temperature of 100 ℃, standing and cooling to room temperature after stirring is finished, separating out substances, performing suction filtration, washing the solid with deionized water until the pH value is unchanged, taking out the solid, and drying at the temperature of 50 ℃, wherein the dried solid is 24-hydroxy-glycyrrhetinic acid, and solid powder of 0.6kg is obtained;
fifthly, 0.6kg of 24 hydroxy-glycyrrhetinic acid is mixed with 0.6kg of stearyl alcohol, 12L of water and 0.06kg of sulfuric acid are added, and the mixture is heated to 100 ℃ and refluxed for 3 hours. Cooling, and pouring out the supernatant to obtain 0.35kg of solid;
sixthly, 0.35kg of solid is heated to 80 ℃ by using 3.5L of 90% ethanol for dissolving, then the solid is cooled to 25 ℃ and crystals are separated out, the solution and the crystals are obtained by filtration, and 0.2kg of 24-hydroxy-stearyl alcohol glycyrrhetinic ester is obtained after the crystals are dried.
Example 2:
firstly, taking 5kg of glycyrrhizin, extracting with 50L of n-butanol, stirring and extracting for 1.5 hours, turning off stirring after 1.5 hours, filtering to remove about 1.89kg of insoluble substances, recording filtrate as filtrate 1, extracting the insoluble substances with 500L of ethyl acetate, stirring and extracting for 1 hour, turning off stirring after one hour, filtering to remove about 1.76kg of insoluble substances, obtaining filtrate 2, and combining filtrate 1 and filtrate 2 to obtain filtrate 3;
secondly, concentrating the extract of the filtrate 3 to 8L at 65 ℃ under reduced pressure, adding 19L of water into the concentrated solution, adding ammonia water, stirring for dissolving, measuring the pH value of the solution to 8.5 after dissolving, adding 19L of acetone into the solution, stirring for 20min, standing for liquid separation, recovering an acetone phase, extracting the water phase with 19L of acetone again, extracting the water phase with diethyl ether and petroleum ether in sequence after extraction, extracting each solvent twice, concentrating the water phase at 60 ℃ under reduced pressure until the solid content is 40%, and spraying at 130 ℃ to obtain 0.95kg of spray powder;
thirdly, adding 27.5L of water into the spray powder obtained in the second step, stirring until the spray powder is dissolved, separating the solution by using HPD-600 type macroporous resin, wherein the volume of a column is 8L, after the column is filled, washing 24L of water to remove impurities with large polarity, eluting by using 40L30% ethanol until no 24-hydroxy-glycyrrhizic acid exists, collecting eluent, and concentrating the eluent under reduced pressure to 2L;
fourthly, adding 6.4L of prepared sulfuric acid aqueous solution with the concentration of 6% into the concentrated solution obtained in the third step, stirring and reacting for 5 hours at the temperature of 100 ℃, standing and cooling to room temperature after stirring is finished, separating out substances, performing suction filtration, washing the solid with deionized water until the pH value is unchanged, taking out the solid, and drying at the temperature of 50 ℃, wherein the dried solid is 20-hydroxy-glycyrrhetinic acid, and solid powder of 0.69kg is obtained;
fifthly, 0.6kg of 24 hydroxy-glycyrrhetinic acid is mixed with 0.6kg of stearyl alcohol, 12L of water and 0.06kg of sulfuric acid are added, and the mixture is heated to 100 ℃ and refluxed for 3 hours. Cooling, and pouring out the supernatant to obtain 0.35kg of solid;
sixthly, 0.35kg of solid is heated to 80 ℃ by using 3.5L of 90% ethanol for dissolving, then the solid is cooled to 25 ℃ and crystals are separated out, the solution and the crystals are obtained by filtration, and 0.2kg of 24-hydroxy-stearyl alcohol glycyrrhetinic ester is obtained after the crystals are dried.
The invention has the following advantages:
1. the liquorice aspartame is used as the raw material, the cost is low, and the liquorice resource is fully utilized;
2. the recovery rate of effective substances is high;
3. the target substance 24-hydroxy-stearyl glycyrrhetinate has good water solubility and lipid solubility.
The invention is not only suitable for the field of food cosmetics, but also suitable for the technical field of medicines.
The present invention is not described in detail in the prior art.
The embodiments selected for the purpose of disclosing the invention, are presently considered to be suitable, it being understood, however, that the invention is intended to cover all variations and modifications of the embodiments which fall within the spirit and scope of the invention.
Claims (10)
1. A preparation method of 24-hydroxystearyl glycyrrhetinate is characterized by comprising the following steps: the preparation method specifically comprises the following steps:
firstly, putting glycyrrhizin into stirring equipment, then adding a proper amount of solvent into the stirring equipment, stirring and extracting for 1-2 hours at normal temperature, wherein the ratio of glycyrrhizin to solvent is 1: 8-1: 10, closing the stirring equipment after extraction is finished, filtering the mixture to remove insoluble substances, retaining filtrate, repeating the steps to extract the glycyrrhizin at least twice, combining the extracting solutions, and concentrating the extracting solution at 60-70 ℃ under reduced pressure to form thick paste;
secondly, adding water with the weight being 4-8 times that of the concentrated thick paste obtained in the previous step, adding ammonia water to dissolve the thick paste to obtain a solution, sequentially extracting the solution with acetone, diethyl ether and petroleum ether in a ratio of 1:1 for 2-3 times, repeatedly extracting each solvent for 2-3 times, concentrating the extracted water phase at 50-70 ℃ under reduced pressure until the solid content is 30-50%, and spraying at 120-140 ℃ to obtain spray powder;
thirdly, adding water into the spray powder obtained in the second step to prepare a 3-5% solution, purifying the solution by using macroporous resin, washing the solution by using 2-8 column volumes of water after the sample loading is finished, eluting the solution by using 30-80% ethanol or methanol as an eluent after the washing to obtain an eluent, and concentrating the eluent to a thick paste under reduced pressure at 50-70 ℃;
fourthly, adding the concentrated thick paste obtained in the third step into sulfuric acid aqueous solution with the weight 6-10 times of that of the concentrated thick paste, stirring and reacting at the temperature of 70-100 ℃ until the reaction is complete, cooling after the reaction is complete, separating out because 24-hydroxy-glycyrrhetinic acid is insoluble in water, cooling to room temperature, performing suction filtration, washing with deionized water until the pH value is unchanged, drying the solid at the temperature of 40-60 ℃, and obtaining the solid which is 24-hydroxy-glycyrrhetinic acid after drying;
fifthly, feeding the 24-hydroxy-glycyrrhetinic acid and stearyl alcohol obtained in the fourth step in proportion, adding water for dissolving, adding sulfuric acid, wherein the amount of the sulfuric acid is 8-12 times of the total amount of dry matters, the amount of the sulfuric acid is 3% -7% of the amount of the dry matters, heating to 90-100 ℃, heating for reflux for 2-4 hours, and collecting solid matters after cooling;
and sixthly, dissolving the solid matter obtained in the fifth step by 8-12 times of high-concentration ethanol at 70-90 ℃, cooling, crystallizing, filtering, dividing into a solution and a crystal, and drying the crystal to obtain the 24-hydroxy-stearyl glycyrrhetinic acid ester.
2. The method of claim 1, wherein the glycyrrhetinic acid 24-hydroxystearyl ester is prepared by: the solvent in the first step is one or the combination of two or more of ethyl acetate, n-butanol or propanol.
3. The method of claim 1, wherein the glycyrrhetinic acid 24-hydroxystearyl ester is prepared by: the solvent in the first step is preferably ethyl acetate.
4. The method of claim 1, wherein the glycyrrhetinic acid 24-hydroxystearyl ester is prepared by: the ratio of glycyrrhizin to solvent in the first step is preferably 1: 8.
5. The method of claim 1, wherein the glycyrrhetinic acid 24-hydroxystearyl ester is prepared by: the pH value of the solution in the second step is 7.5-9.
6. The method of claim 1, wherein the glycyrrhetinic acid 24-hydroxystearyl ester is prepared by: the model of the macroporous resin in the third step is any one of HPD-400, HPD-500, HPD-600, D101 and D1300.
7. The method of claim 1, wherein the glycyrrhetinic acid 24-hydroxystearyl ester is prepared by: the model of the macroporous resin in the third step is preferably D101 type resin.
8. The method of claim 1, wherein the glycyrrhetinic acid 24-hydroxystearyl ester is prepared by: preferably, the elution solvent used in the third step is ethanol.
9. The method of claim 1, wherein the glycyrrhetinic acid 24-hydroxystearyl ester is prepared by: the sulfuric acid concentration of the sulfuric acid aqueous solution in the fourth step is 6-8%.
10. The method of claim 1, wherein the glycyrrhetinic acid 24-hydroxystearyl ester is prepared by: in the fifth step, the feeding ratio of the 24-hydroxy-glycyrrhetinic acid to the stearyl alcohol is 1: 1.
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