CN101456892A - Method for preparing madecassic acid by hydroxyl asiatic centella glycosides basic hydrolysis - Google Patents
Method for preparing madecassic acid by hydroxyl asiatic centella glycosides basic hydrolysis Download PDFInfo
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- PRAUVHZJPXOEIF-AOLYGAPISA-N madecassic acid Chemical compound C1[C@@H](O)[C@H](O)[C@@](C)(CO)[C@@H]2[C@H](O)C[C@@]3(C)[C@]4(C)CC[C@@]5(C(O)=O)CC[C@@H](C)[C@H](C)[C@H]5C4=CC[C@@H]3[C@]21C PRAUVHZJPXOEIF-AOLYGAPISA-N 0.000 title claims abstract description 94
- 230000007062 hydrolysis Effects 0.000 title claims abstract description 47
- 238000006460 hydrolysis reaction Methods 0.000 title claims abstract description 47
- 238000000034 method Methods 0.000 title claims abstract description 26
- 229940011656 madecassic acid Drugs 0.000 title claims description 83
- BUWCHLVSSFQLPN-UHFFFAOYSA-N madecassic acid Natural products CC1CCC2(CCC3(C)C(=CCC4C5(C)CC(O)C(O)C(C)(C5CCC34C)C(=O)O)C2C1C)C(=O)OC6OC(COC7OC(CO)C(OC8OC(C)C(O)C(O)C8O)C(O)C7O)C(O)C(O)C6O BUWCHLVSSFQLPN-UHFFFAOYSA-N 0.000 title claims description 83
- 241000167550 Centella Species 0.000 title claims description 14
- 125000002887 hydroxy group Chemical group [H]O* 0.000 title claims description 14
- 229930182470 glycoside Natural products 0.000 title claims description 13
- 150000002338 glycosides Chemical class 0.000 title claims description 13
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 95
- 239000000047 product Substances 0.000 claims abstract description 57
- 238000001914 filtration Methods 0.000 claims abstract description 51
- QCYLIQBVLZBPNK-UHFFFAOYSA-N asiaticoside A Natural products O1C(C(=O)C(C)C)=CC(C)C(C2(C(OC(C)=O)CC34C5)C)C1CC2(C)C3CCC(C1(C)C)C45CCC1OC1OCC(O)C(O)C1O QCYLIQBVLZBPNK-UHFFFAOYSA-N 0.000 claims abstract description 45
- 239000002994 raw material Substances 0.000 claims abstract description 33
- 239000007864 aqueous solution Substances 0.000 claims abstract description 28
- 238000002425 crystallisation Methods 0.000 claims abstract description 27
- 230000008025 crystallization Effects 0.000 claims abstract description 27
- 239000000243 solution Substances 0.000 claims abstract description 27
- 239000000706 filtrate Substances 0.000 claims abstract description 26
- 239000003513 alkali Substances 0.000 claims abstract description 10
- 239000003960 organic solvent Substances 0.000 claims abstract description 9
- 239000002253 acid Substances 0.000 claims abstract description 6
- 238000004090 dissolution Methods 0.000 claims abstract description 3
- WYQVAPGDARQUBT-FGWHUCSPSA-N Madecassol Chemical compound O([C@@H]1[C@@H](CO)O[C@H]([C@@H]([C@H]1O)O)OC[C@H]1O[C@H]([C@@H]([C@@H](O)[C@@H]1O)O)OC(=O)[C@]12CC[C@H]([C@@H]([C@H]1C=1[C@@]([C@@]3(CC[C@H]4[C@](C)(CO)[C@@H](O)[C@H](O)C[C@]4(C)[C@H]3CC=1)C)(C)CC2)C)C)[C@@H]1O[C@@H](C)[C@H](O)[C@@H](O)[C@H]1O WYQVAPGDARQUBT-FGWHUCSPSA-N 0.000 claims description 42
- WYQVAPGDARQUBT-XCWYDTOWSA-N asiaticoside Natural products O=C(O[C@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO[C@H]2[C@H](O)[C@H](O)[C@H](O[C@H]3[C@H](O)[C@H](O)[C@@H](O)[C@H](C)O3)[C@@H](CO)O2)O1)[C@@]12[C@@H]([C@@H](C)[C@H](C)CC1)C=1[C@](C)([C@@]3(C)[C@@H]([C@@]4(C)[C@H]([C@@](CO)(C)[C@@H](O)[C@H](O)C4)CC3)CC=1)CC2 WYQVAPGDARQUBT-XCWYDTOWSA-N 0.000 claims description 42
- 229940022757 asiaticoside Drugs 0.000 claims description 42
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 39
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 30
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 26
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 claims description 26
- 238000000247 postprecipitation Methods 0.000 claims description 24
- 238000001291 vacuum drying Methods 0.000 claims description 24
- 229910052500 inorganic mineral Inorganic materials 0.000 claims description 8
- 239000011707 mineral Substances 0.000 claims description 8
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 6
- PRAUVHZJPXOEIF-UHFFFAOYSA-N madecassica acid Natural products C1C(O)C(O)C(C)(CO)C2C(O)CC3(C)C4(C)CCC5(C(O)=O)CCC(C)C(C)C5C4=CCC3C21C PRAUVHZJPXOEIF-UHFFFAOYSA-N 0.000 abstract description 6
- BNMGUJRJUUDLHW-HCZMHFOYSA-N Madecassoside Chemical compound O([C@@H]1[C@@H](CO)O[C@H]([C@@H]([C@H]1O)O)OC[C@H]1O[C@H]([C@@H]([C@@H](O)[C@@H]1O)O)OC(=O)[C@]12CC[C@H]([C@@H]([C@H]1C=1[C@@]([C@@]3(C[C@@H](O)[C@H]4[C@](C)(CO)[C@@H](O)[C@H](O)C[C@]4(C)[C@H]3CC=1)C)(C)CC2)C)C)[C@@H]1O[C@@H](C)[C@H](O)[C@@H](O)[C@H]1O BNMGUJRJUUDLHW-HCZMHFOYSA-N 0.000 abstract description 5
- 239000003814 drug Substances 0.000 abstract description 5
- 239000013078 crystal Substances 0.000 abstract description 4
- BNMGUJRJUUDLHW-HLUHVYOBSA-N Madecassoside Natural products C[C@@H]1CC[C@@]2(CC[C@]3(C)C(=CC[C@@H]4[C@@]5(C)C[C@@H](O)[C@H](O)[C@@](C)(CO)[C@@H]5[C@H](O)C[C@@]34C)[C@@H]2[C@H]1C)C(=O)O[C@@H]6O[C@H](CO[C@@H]7O[C@H](CO)[C@@H](O[C@@H]8O[C@H](C)[C@H](O)[C@@H](O)[C@H]8O)[C@H](O)[C@H]7O)[C@@H](O)[C@H](O)[C@H]6O BNMGUJRJUUDLHW-HLUHVYOBSA-N 0.000 abstract description 3
- 229940079593 drug Drugs 0.000 abstract description 3
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- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
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- PZIRUHCJZBGLDY-UHFFFAOYSA-N Caffeoylquinic acid Natural products CC(CCC(=O)C(C)C1C(=O)CC2C3CC(O)C4CC(O)CCC4(C)C3CCC12C)C(=O)O PZIRUHCJZBGLDY-UHFFFAOYSA-N 0.000 description 1
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- 206010027249 Meningitis meningococcal Diseases 0.000 description 1
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- CWVRJTMFETXNAD-KLZCAUPSSA-N Neochlorogenin-saeure Natural products O[C@H]1C[C@@](O)(C[C@@H](OC(=O)C=Cc2ccc(O)c(O)c2)[C@@H]1O)C(=O)O CWVRJTMFETXNAD-KLZCAUPSSA-N 0.000 description 1
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 1
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- 229940011658 asiatic acid Drugs 0.000 description 1
- LBGFKBYMNRAMFC-PYSQTNCISA-N asiatic acid Natural products C[C@@H]1CC[C@@]2(CC[C@]3(C)C(=CC[C@@H]4[C@@]5(C)C[C@@H](O)[C@H](O)[C@@](C)(CO)[C@@H]5CC[C@@]34C)[C@]2(C)[C@H]1C)C(=O)O LBGFKBYMNRAMFC-PYSQTNCISA-N 0.000 description 1
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- CWVRJTMFETXNAD-JUHZACGLSA-N chlorogenic acid Chemical compound O[C@@H]1[C@H](O)C[C@@](O)(C(O)=O)C[C@H]1OC(=O)\C=C\C1=CC=C(O)C(O)=C1 CWVRJTMFETXNAD-JUHZACGLSA-N 0.000 description 1
- 229940074393 chlorogenic acid Drugs 0.000 description 1
- FFQSDFBBSXGVKF-KHSQJDLVSA-N chlorogenic acid Natural products O[C@@H]1C[C@](O)(C[C@@H](CC(=O)C=Cc2ccc(O)c(O)c2)[C@@H]1O)C(=O)O FFQSDFBBSXGVKF-KHSQJDLVSA-N 0.000 description 1
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- ATNHDLDRLWWWCB-AENOIHSZSA-M chlorophyll a Chemical compound C1([C@@H](C(=O)OC)C(=O)C2=C3C)=C2N2C3=CC(C(CC)=C3C)=[N+]4C3=CC3=C(C=C)C(C)=C5N3[Mg-2]42[N+]2=C1[C@@H](CCC(=O)OC\C=C(/C)CCC[C@H](C)CCC[C@H](C)CCCC(C)C)[C@H](C)C2=C5 ATNHDLDRLWWWCB-AENOIHSZSA-M 0.000 description 1
- BMRSEYFENKXDIS-KLZCAUPSSA-N cis-3-O-p-coumaroylquinic acid Natural products O[C@H]1C[C@@](O)(C[C@@H](OC(=O)C=Cc2ccc(O)cc2)[C@@H]1O)C(=O)O BMRSEYFENKXDIS-KLZCAUPSSA-N 0.000 description 1
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- WQLVFSAGQJTQCK-UHFFFAOYSA-N diosgenin Natural products CC1C(C2(CCC3C4(C)CCC(O)CC4=CCC3C2C2)C)C2OC11CCC(C)CO1 WQLVFSAGQJTQCK-UHFFFAOYSA-N 0.000 description 1
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Landscapes
- Steroid Compounds (AREA)
Abstract
The invention discloses a method for preparing brahmic acid by alkali hydrolysis of madecassoside, which comprises the following steps: 1) adding madecassoside raw material into an aqueous solution of inorganic base in batch for hydrolysis at a temperature of between 45 and 90 DEG C for 1 to 24 hours; 2) adding acid into the hydrolysate solution to adjust the pH value to be 2-4, depositing and filtering the hydrolysate solution to obtain deposit; and 3) drying the deposit, adding the deposit into an organic solvent for dissolution, filtering the solution, adding water into filtrate for crystallization, filtering the filtrate to obtain crystals, and drying the crystals in vacuum to obtain the brahmic acid product. The brahmic acid product has high yield and purity, and can be used for preparing bulk drug or derivatives of the brahmic acid; meanwhile, the method has simple technological process, small investment, and easy industrialization.
Description
Technical field
The present invention relates to a kind of method of preparing madecassic acid by hydroxyl asiatic centella glycosides basic hydrolysis.
Background technology
Herba Centellae [Centella asiatica (L.) Urban] is a umbelliferae Centella plant, and the traditional medicine Application for Field has long history in many countries and regions, and China's traditional Chinese medicine is to the existing bimillennial history of for oral administration and external application of Herba Centellae.Herba Centellae bitter, suffering, cold in nature, return liver,spleen,kidney, stomach warp.The record of Gu pharmacopeia is mainly used in illnesss such as treatment jaundice due to damp-heat, heatstroke diarrhoea, the pouring of sand pouring blood, carbuncle sore tumefacting virus, wound.Modern pharmacology research and application show that Herba Centellae can be used for treating dysthymia disorders, skin wound, stomach ulcer, infectious hepatitis, tetter and meningococcal meningitis etc.
The pharmacological action of Herba Centellae is inseparable with its chemical ingredients.The chemical ingredients of Herba Centellae is very complicated, and its main component has triterpenes, polyyne olefines, flavonoid and volatile oil etc.In addition, also contain compositions such as chlorogenic acid, meso-inositol, flavonol, lipid acid, Lawn Pennywort Herb alkali, sterol, wax, chlorophyll, hydro carbons, lignanoids, sugar, tannin and polyatomic phenol in the Herba Centellae.In the chemical ingredients of Herba Centellae, triterpenes saponin(e and sapogenin thereof be research the earliest, the more deep big class component of biological activity research, wherein asiaticoside, Madecassic acid are its important activeconstituentss.
Asiaticoside (Madecassoside, claim again: O-6-Deoxy-alpha-L-mannopyranosyl-(1.4)-O-beta-D-glucopyranosyl-(1.6)-beta-D-glucopyranosyl (2alpha, 3beta, 4alpha, 6beta)-2,3,6,23-tetrahydroxyurs-12-en-28-oate, CASNo.:34540-22-2), white, needle-shaped crystals, molecular formula are C
48H
78O
20, molecular weight is 975.12, the little hardship of mouthfeel, and 220～223 ℃ of fusing points, asiaticoside is soluble,very slightly in water, is dissolved in ethanol and pyridine.(Madecassic acid has another name called Madecassic acid: Brahmic acid; 8,10,11-trihydroxy-9-(hydroxymethyl)-1,2,6a, 6b, 9,12a-hexamethyl-2,3,4,5,6,6a, 7,8,8a, 10,11,12,13,14b-tetradecahydro-1H-picene-4a-carboxylic acid, CASNo.:18449-41-7) be white, needle-shaped crystals, odorless, bitter, molecular formula is C
30H
48O
6, molecular weight is 504.70,265～268 ℃ of fusing points, and Madecassic acid is water insoluble, is dissolved in ethanol.The pentacyclic triterpene that belongs to the ursane type on asiaticoside and the Madecassic acid structure, its structural formula is as follows respectively:
The structural formula of the structural formula Madecassic acid of asiaticoside
Studies show that Madecassic acid has antidepressant, effect such as antibiotic and anti-oxidant, and hypertension is had certain therapeutic action.And, from Madecassic acid, can prepare a series of Madecassic acid derivatives by semi-synthetic, as described in patent CN1347398, obtain the derivative of the Madecassic acid salt on 17 carboxyls of part of hydroxyl asiatic acid E ring, found the antidepressant effect increase in various degree of these products.In addition, these derivatives also can be used for treating the pharmaceutical composition of erythema, burn, skin-nourishing disease etc. and the make-up composition of treatment inflammation, thereby overcome the insufficient shortcoming of asiaticoside preparation stability, improved the bioavailability of Madecassic acid effectively, for the exploitation of the relevant new drug of Herba Centellae provides wide prospect.Therefore, the preparation of Madecassic acid has great importance to utilizing the Herba Centellae resource better.
At present, the Madecassic acid preparation method directly extracts from the grass of accumulated snow grassland, obtains through separation purge process such as loaded down with trivial details extraction, chromatography, crystallization, comparatively wastes time and energy.Data shows that the Madecassic acid content in the Herba Centellae is starkly lower than the content of asiaticoside, and the amount of the Madecassic acid that directly obtains from Herba Centellae is less relatively; Asiaticoside is than facile hydrolysis in addition, and therefore being hydrolyzed and obtaining Madecassic acid from asiaticoside is a kind of valid approach.
The present invention's plan hydrolysis asiaticoside in the aqueous solution of mineral alkali prepares Madecassic acid in conjunction with crystallization processes.Madecassic acid product yield of the present invention and purity height, product can be used as the preparation of bulk drug or Madecassic acid derivative; Simultaneously simple, the required less investment of this method technological process, be easy to realize industrialization.
Summary of the invention
The objective of the invention is to overcome the deficiencies in the prior art, a kind of method of preparing madecassic acid by hydroxyl asiatic centella glycosides basic hydrolysis is provided.
The step of method is as follows:
1) in the aqueous solution of mineral alkali, adds the asiaticoside raw material, at 45～90 ℃ of following hydrolysis 1～24h in batches;
2) hydrolyzed solution adds acid, regulates pH value to 2～4, and post precipitation filters, and gets throw out;
3) throw out dries back adding organic solvent dissolution, filtration, and filtrate adds water crystallization, gets crystallisate after filtering, and crystallisate gets the Madecassic acid product again after vacuum-drying.
Wherein used mineral alkali is NaOH, KOH or Na in the step 1)
2CO
3, the concentration of mineral alkali is 0.1～2mol/L in the inorganic base aqueous solution; Hydrolysis temperature is 45～90 ℃, and wherein preferred temperature is 55～80 ℃; Hydrolysis time is 1～24h, and wherein preferable hydrolysis time is 2～15h; Step 2) regulating the used acid of pH value in is hydrochloric acid or sulfuric acid; Organic solvent in the step 3) is ethanol or methyl alcohol, and the consumption of organic solvent is 5～30mL/g throw out (weighing after drying); The consumption of water is 8～16 times of organic solvent volume in the step 3).
The asiaticoside raw material adopts batch mode to join in the aqueous solution of mineral alkali in the step 1), according to 2～5 batches of the unusual branches of asiaticoside raw material add-on, the reinforced time generally be controlled at the reaction times 30% in.
Madecassic acid product yield of the present invention and purity height (Madecassic acid mass content 〉=90%), product can be used as the preparation of bulk drug or Madecassic acid derivative; Simultaneously simple, the required less investment of this method technological process, be easy to realize industrialization.
Description of drawings
Accompanying drawing is the process flow diagram of preparing madecassic acid by hydroxyl asiatic centella glycosides basic hydrolysis.
Embodiment
Asiaticoside raw material used in the present invention is available from the natural pharmaceutcal corporation, Ltd of Guangxi Chang Zhou, and the mass content of asiaticoside is 90.1% after testing.
Asiaticoside and Madecassic acid content adopt high performance liquid chromatography (HPLC) to measure, and adopt external standard method quantitative.Adopt Agilent1100 liquid-phase chromatographic analysis system, analysis condition is as follows: Eclipse XDB-C
18Reversed-phase column (Φ 4.6mm * 250mm, 5 μ m, Agilent); Adopt gradient elution, flow velocity 0.6mL/min; Column temperature is 35 ℃; Detect wavelength 210nm.
Table 1 HPLC method is measured the eluent gradient of asiaticoside and Madecassic acid
Below with embodiment processing method of the present invention is further described.Protection scope of the present invention is not subjected to the restriction of embodiment, and protection scope of the present invention is determined by claims.
The calculation formula of yield is as follows among the embodiment:
The theoretical yield of the mass content of Madecassic acid/Madecassic acid product in the amount * product of yield=Madecassic acid product
Mass content * the 504.7/975.12 of the amount * asiaticoside of the theoretical yield of Madecassic acid product=asiaticoside raw material
Embodiment 1
In the there-necked flask of stirring of 1L band and water condensing tube, add 0.1mol/LNaOH aqueous solution 500mL, put into 90 ℃ water bath with thermostatic control, open and stir and water of condensation, divide 2 batches to add asiaticoside raw material 10g (adding is second crowd behind the reaction 2h), hydrolysis 8h; Hydrolyzed solution adds hydrochloric acid, regulates pH value to 2～4, and post precipitation filters, must throw out, weigh after throw out dries 5.3g; Throw out after collection is dried adds 26.5mL dissolve with methanol, filtration, filtrate adds the 212mL water crystallization, gets crystallisate after filtering, and crystallisate gets 3.2g Madecassic acid product again after vacuum-drying, product is through the mass content 82.6% of HPLC analysis Madecassic acid, yield 56.7%.
Embodiment 2
In the there-necked flask of stirring of 1L band and water condensing tube, add 0.3mol/LKOH aqueous solution 500mL, put into 85 ℃ water bath with thermostatic control, open and stir and water of condensation, divide 3 batches to add asiaticoside raw material 20g (always the reinforced time is 1h), hydrolysis 4h; Hydrolyzed solution adds sulfuric acid, regulates pH value to 2～4, and post precipitation filters, must throw out, weigh after throw out dries 10.1g; Throw out after collection is dried adds 101mL dissolve with ethanol, filtration, filtrate adds the 1010mL water crystallization, gets crystallisate after filtering, and crystallisate gets 7.3g Madecassic acid product again after vacuum-drying, product is through the mass content 90.5% of HPLC analysis Madecassic acid, yield 70.8%.
Embodiment 3
In the there-necked flask of stirring of 1L band and water condensing tube, add 0.5mol/LNa
2CO
3Aqueous solution 500mL puts into 80 ℃ water bath with thermostatic control, opens and stirs and water of condensation, divides 4 batches to add asiaticoside raw material 30g (time of always feeding in raw material is 1.5h), hydrolysis 5h; Hydrolyzed solution adds hydrochloric acid, regulates pH value to 2～4, and post precipitation filters, must throw out, weigh after throw out dries 15.4g; Throw out after collection is dried adds 231mL dissolve with ethanol, filtration, filtrate adds the 2772mL water crystallization, gets crystallisate after filtering, and crystallisate gets 11.0g Madecassic acid product again after vacuum-drying, product is through the mass content 91.2% of HPLC analysis Madecassic acid, yield 71.7%.
Embodiment 4
In the there-necked flask of stirring of 1L band and water condensing tube, add 0.7mol/LNaOH aqueous solution 500mL, put into 75 ℃ water bath with thermostatic control, open and stir and water of condensation, divide 5 batches to add asiaticoside raw material 40g (always the reinforced time is 1.5h), hydrolysis 5h; Hydrolyzed solution adds sulfuric acid, regulates pH value to 2～4, and post precipitation filters, must throw out, weigh after throw out dries 20.5g; Throw out after collection is dried adds 410mL dissolve with methanol, filtration, filtrate adds the 5740mL water crystallization, gets crystallisate after filtering, and crystallisate gets 14.1g Madecassic acid product again after vacuum-drying, product is through the mass content 91.4% of HPLC analysis Madecassic acid, yield 69.1%.
Embodiment 5
In the there-necked flask of stirring of 1L band and water condensing tube, add 0.9mol/LKOH aqueous solution 500mL, put into 70 ℃ water bath with thermostatic control, open and stir and water of condensation, divide 6 batches to add asiaticoside raw material 50g (always the reinforced time is 1.5h), hydrolysis 5h; Hydrolyzed solution adds hydrochloric acid, regulates pH value to 2～4, and post precipitation filters, must throw out, weigh after throw out dries 25.4g; Throw out after collection is dried adds 635mL dissolve with methanol, filtration, filtrate adds the 10160mL water crystallization, get crystallisate after filtering, crystallisate gets 19.2g Madecassic acid product again after vacuum-drying, product is through the mass content 89.5% of HPLC analysis Madecassic acid, yield 73.3%.
Embodiment 6
In the there-necked flask of stirring of 1L band and water condensing tube, add 1.1mol/LNa
2CO
3Aqueous solution 500mL puts into 65 ℃ water bath with thermostatic control, opens and stirs and water of condensation, divides 2 batches to add asiaticoside raw material 10g (adding is second crowd behind the reaction 1.5h), hydrolysis 6h; Hydrolyzed solution adds sulfuric acid, regulates pH value to 2～4, and post precipitation filters, must throw out, weigh after throw out dries 5.1g; Throw out after collection is dried adds 153mL dissolve with ethanol, filtration, filtrate adds the 2754mL water crystallization, gets crystallisate after filtering, and crystallisate gets 3.1g Madecassic acid product again after vacuum-drying, product is through the mass content 91.0% of HPLC analysis Madecassic acid, yield 60.5%.
Embodiment 7
In the there-necked flask of stirring of 1L band and water condensing tube, add 1.3mol/LNaOH aqueous solution 500mL, put into 60 ℃ water bath with thermostatic control, open and stir and water of condensation, divide 3 batches to add asiaticoside raw material 20g (always the reinforced time is 2h), hydrolysis 8h; Hydrolyzed solution adds hydrochloric acid, regulates pH value to 2～4, and post precipitation filters, must throw out, weigh after throw out dries 10.2g; Throw out after collection is dried adds 51mL dissolve with ethanol, filtration, filtrate adds the 918mL water crystallization, gets crystallisate after filtering, and crystallisate gets 6.7g Madecassic acid product again after vacuum-drying, product is through the mass content 91.3% of HPLC analysis Madecassic acid, yield 65.6%.
Embodiment 8
In the there-necked flask of stirring of 1L band and water condensing tube, add 1.5mol/LKOH aqueous solution 500mL, put into 55 ℃ water bath with thermostatic control, open and stir and water of condensation, divide 4 batches to add asiaticoside raw material 30g (always the reinforced time is 3h), hydrolysis 10h; Hydrolyzed solution adds sulfuric acid, regulates pH value to 2～4, and post precipitation filters, must throw out, weigh after throw out dries 15.3g; Throw out after collection is dried adds 153mL dissolve with methanol, filtration, filtrate adds the 2448mL water crystallization, gets crystallisate after filtering, and crystallisate gets 10.2g Madecassic acid product again after vacuum-drying, product is through the mass content 90.7% of HPLC analysis Madecassic acid, yield 66.1%.
Embodiment 9
In the there-necked flask of stirring of 1L band and water condensing tube, add 1.7mol/L KOH aqueous solution 500mL, put into 50 ℃ water bath with thermostatic control, open and stir and water of condensation, divide 5 batches to add asiaticoside raw material 40g (always the reinforced time is 4.5h), hydrolysis 15h; Hydrolyzed solution adds hydrochloric acid, regulates pH value to 2～4, and post precipitation filters, must throw out, weigh after throw out dries 21.3g; Throw out after collection is dried adds 319.5mL dissolve with methanol, filtration, filtrate adds the 4473mL water crystallization, get crystallisate after filtering, crystallisate gets 15.0g Madecassic acid product again after vacuum-drying, product is through the mass content 85.7% of HPLC analysis Madecassic acid, yield 68.9%.
Embodiment 10
In the there-necked flask of stirring of 1L band and water condensing tube, add 2mol/LNaOH aqueous solution 500mL, put into 45 ℃ water bath with thermostatic control, open and stir and water of condensation, divide 6 batches to add asiaticoside raw material 50g (always the reinforced time is 7h), hydrolysis 24h; Hydrolyzed solution adds sulfuric acid, regulates pH value to 2～4, and post precipitation filters, must throw out, weigh after throw out dries 26.2g; Throw out after collection is dried adds 524mL dissolve with ethanol, filtration, filtrate adds the 6288mL water crystallization, gets crystallisate after filtering, and crystallisate gets 18.4g Madecassic acid product again after vacuum-drying, product is through the mass content 80.1% of HPLC analysis Madecassic acid, yield 63.2%.
Embodiment 11
In the there-necked flask of stirring of 1L band and water condensing tube, add 0.5mol/LKOH aqueous solution 500mL, put into 55 ℃ water bath with thermostatic control, open and stir and water of condensation, divide 3 batches to add asiaticoside raw material 20g (always the reinforced time is 3h), hydrolysis 12h; Hydrolyzed solution adds hydrochloric acid, regulates pH value to 2～4, and post precipitation filters, must throw out, weigh after throw out dries 10.3g; Throw out after collection is dried adds 257.5mL dissolve with ethanol, filtration, filtrate adds the 2575mL water crystallization, get crystallisate after filtering, crystallisate gets 7.0g Madecassic acid product again after vacuum-drying, product is through the mass content 90.1% of HPLC analysis Madecassic acid, yield 67.6%.
Embodiment 12
In the there-necked flask of stirring of 1L band and water condensing tube, add 1.0mol/L Na
2CO
3Aqueous solution 500mL puts into 60 ℃ water bath with thermostatic control, opens and stirs and water of condensation, divides 4 batches to add asiaticoside raw material 30g (time of always feeding in raw material is 2h), hydrolysis 8h; Hydrolyzed solution adds sulfuric acid, regulates pH value to 2～4, and post precipitation filters, must throw out, weigh after throw out dries 15.2g; Throw out after collection is dried adds 456mL dissolve with methanol, filtration, filtrate adds the 3648mL water crystallization, gets crystallisate after filtering, and crystallisate gets 11.1g Madecassic acid product again after vacuum-drying, product is through the mass content 90.8% of HPLC analysis Madecassic acid, yield 72.0%.
Embodiment 13
In the there-necked flask of stirring of 1L band and water condensing tube, add 1.5mol/LNaOH aqueous solution 500mL, put into 65 ℃ water bath with thermostatic control, open and stir and water of condensation, divide 5 batches to add asiaticoside raw material 40g (always the reinforced time is 1.5h), hydrolysis 6h; Hydrolyzed solution adds hydrochloric acid, regulates pH value to 2～4, and post precipitation filters, must throw out, weigh after throw out dries 20.1g; Throw out after collection is dried adds 100.5mL dissolve with methanol, filtration, filtrate adds the 1005mL water crystallization, get crystallisate after filtering, crystallisate gets 14.8g Madecassic acid product again after vacuum-drying, product is through the mass content 91.2% of HPLC analysis Madecassic acid, yield 72.4%.
Embodiment 14
In the there-necked flask of stirring of 1L band and water condensing tube, add 0.2mol/LKOH aqueous solution 500mL, put into 70 ℃ water bath with thermostatic control, open and stir and water of condensation, divide 3 batches to add asiaticoside raw material 20g (always the reinforced time is 2h), hydrolysis 8h; Hydrolyzed solution adds sulfuric acid, regulates pH value to 2～4, and post precipitation filters, must throw out, weigh after throw out dries 10.2g; Throw out after collection is dried adds 102mL dissolve with ethanol, filtration, filtrate adds the 1224mL water crystallization, gets crystallisate after filtering, and crystallisate gets 7.0g Madecassic acid product again after vacuum-drying, product is through the mass content 91.5% of HPLC analysis Madecassic acid, yield 68.7%.
Embodiment 15
In the there-necked flask of stirring of 1L band and water condensing tube, add 0.4mol/LNa
2CO
3Aqueous solution 500mL puts into 75 ℃ water bath with thermostatic control, opens and stirs and water of condensation, divides 4 batches to add asiaticoside raw material 30g (time of always feeding in raw material is 1.5h), hydrolysis 6h; Hydrolyzed solution adds hydrochloric acid, regulates pH value to 2～4, and post precipitation filters, must throw out, weigh after throw out dries 15.1g; Throw out after collection is dried adds 226.5mL dissolve with ethanol, filtration, filtrate adds the 3171mL water crystallization, get crystallisate after filtering, crystallisate gets 11.4g Madecassic acid product again after vacuum-drying, product is through the mass content 90.3% of HPLC analysis Madecassic acid, yield 73.6%.
Embodiment 16
In the there-necked flask of stirring of 1L band and water condensing tube, add 0.6mol/LNaOH aqueous solution 500mL, put into 80 ℃ water bath with thermostatic control, open and stir and water of condensation, divide 5 batches to add asiaticoside raw material 40g (always the reinforced time is 1h), hydrolysis 4h; Hydrolyzed solution adds sulfuric acid, regulates pH value to 2～4, and post precipitation filters, must throw out, weigh after throw out dries 20.4g; Throw out after collection is dried adds 408mL dissolve with methanol, filtration, filtrate adds the 6528mL water crystallization, gets crystallisate after filtering, and crystallisate gets 15.1g Madecassic acid product again after vacuum-drying, product is through the mass content 91.6% of HPLC analysis Madecassic acid, yield 74.2%.
Embodiment 17
In the there-necked flask of stirring of 1L band and water condensing tube, add 0.8mol/LKOH aqueous solution 500mL, put into 60 ℃ water bath with thermostatic control, open and stir and water of condensation, divide 3 batches to add asiaticoside raw material 20g (always the reinforced time is 1.5h), hydrolysis 6h; Hydrolyzed solution adds hydrochloric acid, regulates pH value to 2～4, and post precipitation filters, must throw out, weigh after throw out dries 10.2g; Throw out after collection is dried adds 255mL dissolve with methanol, filtration, filtrate adds the 2550mL water crystallization, gets crystallisate after filtering, and crystallisate gets 7.3g Madecassic acid product again after vacuum-drying, product is through the mass content 92.0% of HPLC analysis Madecassic acid, yield 72.0%.
Embodiment 18
In the there-necked flask of stirring of 1L band and water condensing tube, add 1.0mol/LNa
2CO
3Aqueous solution 500mL puts into 65 ℃ water bath with thermostatic control, opens and stirs and water of condensation, divides 4 batches to add asiaticoside raw material 30g (time of always feeding in raw material is 1.5h), hydrolysis 5h; Hydrolyzed solution adds sulfuric acid, regulates pH value to 2～4, and post precipitation filters, must throw out, weigh after throw out dries 15.5g; Throw out after collection is dried adds 465mL dissolve with ethanol, filtration, filtrate adds the 5580mL water crystallization, gets crystallisate after filtering, and crystallisate gets 11.0g Madecassic acid product again after vacuum-drying, product is through the mass content 91.5% of HPLC analysis Madecassic acid, yield 71.9%.
Embodiment 19
In the there-necked flask of stirring of 1L band and water condensing tube, add 0.6mol/LNaOH aqueous solution 500mL, put into 70 ℃ water bath with thermostatic control, open and stir and water of condensation, divide 5 batches to add asiaticoside raw material 40g (always the reinforced time is 1h), hydrolysis 4h; Hydrolyzed solution adds hydrochloric acid, regulates pH value to 2～4, and post precipitation filters, must throw out, weigh after throw out dries 20.2g; Throw out after collection is dried adds 202mL dissolve with ethanol, filtration, filtrate adds the 2828mL water crystallization, gets crystallisate after filtering, and crystallisate gets 15.1g Madecassic acid product again after vacuum-drying, product is through the mass content 92.1% of HPLC analysis Madecassic acid, yield 74.6%.
Embodiment 20
In the there-necked flask of stirring of 1L band and water condensing tube, add 0.5mol/LKOH aqueous solution 500mL, put into 75 ℃ water bath with thermostatic control, open and stir and water of condensation, divide 3 batches to add asiaticoside raw material 20g (always the reinforced time is 45min), hydrolysis 3h; Hydrolyzed solution adds sulfuric acid, regulates pH value to 2～4, and post precipitation filters, must throw out, weigh after throw out dries 10.4g; Throw out after collection is dried adds 156mL dissolve with methanol, filtration, filtrate adds the 2496mL water crystallization, gets crystallisate after filtering, and crystallisate gets 7.5g Madecassic acid product again after vacuum-drying, product is through the mass content 91.8% of HPLC analysis Madecassic acid, yield 73.8%.
Embodiment 21
In the there-necked flask of stirring of 1L band and water condensing tube, add 0.4mol/LNaOH aqueous solution 500mL, put into 80 ℃ water bath with thermostatic control, open and stir and water of condensation, divide 4 batches to add asiaticoside raw material 30g (always the reinforced time is 30min), hydrolysis 2h; Hydrolyzed solution adds hydrochloric acid, regulates pH value to 2～4, and post precipitation filters, must throw out, weigh after throw out dries 15.5g; Throw out after collection is dried adds 310mL dissolve with methanol, filtration, filtrate adds the 3720mL water crystallization, gets crystallisate after filtering, and crystallisate gets 11.3g Madecassic acid product again after vacuum-drying, product is through the mass content 91.3% of HPLC analysis Madecassic acid, yield 73.7%.
Embodiment 22
In the there-necked flask of stirring of 1L band and water condensing tube, add 1.5mol/LKOH aqueous solution 500mL, put into 90 ℃ water bath with thermostatic control, open and stir and water of condensation, divide 2 batches to add asiaticoside raw material 10g (adding is second crowd behind the reaction 15min), hydrolysis 1h; Hydrolyzed solution adds sulfuric acid, regulates pH value to 2～4, and post precipitation filters, must throw out, weigh after throw out dries 4.9g; Throw out after collection is dried adds 122.5mL dissolve with ethanol, filtration, filtrate adds the 1715mL water crystallization, get crystallisate after filtering, crystallisate gets 2.8g Madecassic acid product again after vacuum-drying, product is through the mass content 88.3% of HPLC analysis Madecassic acid, yield 53.0%.
Claims (9)
1. the method for a preparing madecassic acid by hydroxyl asiatic centella glycosides basic hydrolysis is characterized in that, the step of method is as follows:
1) in the aqueous solution of mineral alkali, adds the asiaticoside raw material, at 45～90 ℃ of following hydrolysis 1～24h in batches;
2) hydrolyzed solution adds acid, regulates pH value to 2～4, and post precipitation filters, and gets throw out;
3) throw out dries back adding organic solvent dissolution, filtration, and filtrate adds water crystallization, gets crystallisate after filtering, and crystallisate gets the Madecassic acid product again after vacuum-drying.
2. the method for a kind of preparing madecassic acid by hydroxyl asiatic centella glycosides basic hydrolysis according to claim 1 is characterized in that the mineral alkali in the step 1) is NaOH, KOH or Na
2CO
3
3. the method for a kind of preparing madecassic acid by hydroxyl asiatic centella glycosides basic hydrolysis according to claim 1, the concentration that it is characterized in that the mineral alkali in the step 1) is 0.1～2mol/L.
4. the method for a kind of preparing madecassic acid by hydroxyl asiatic centella glycosides basic hydrolysis according to claim 1 is characterized in that the hydrolysis temperature in the step 1) is 55～80 ℃.
5. the method for a kind of preparing madecassic acid by hydroxyl asiatic centella glycosides basic hydrolysis according to claim 1 is characterized in that the hydrolysis time in the step 1) is 2～15h.
6. the method for a kind of preparing madecassic acid by hydroxyl asiatic centella glycosides basic hydrolysis according to claim 1 is characterized in that step 2) in the used acid of adjusting pH value be hydrochloric acid or sulfuric acid.
7. the method for a kind of preparing madecassic acid by hydroxyl asiatic centella glycosides basic hydrolysis according to claim 1 is characterized in that the organic solvent in the step 3) is ethanol or methyl alcohol.
8. a kind of hydroxyl Herba Centellae according to claim 1
Basic hydrolysis prepares the method for Madecassic acid, and the consumption that it is characterized in that the organic solvent in the step 3) is 5～30mL/g throw out.
9. the method for a kind of preparing madecassic acid by hydroxyl asiatic centella glycosides basic hydrolysis according to claim 1, the consumption that it is characterized in that the water in the step 3) is 8～16 times of organic solvent volume.
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| CN106366153A (en) * | 2016-08-25 | 2017-02-01 | 桂林益天成生物科技有限公司 | Method of preparing madecassic acid by hydrolyzing madecassoside |
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| CN106366153A (en) * | 2016-08-25 | 2017-02-01 | 桂林益天成生物科技有限公司 | Method of preparing madecassic acid by hydrolyzing madecassoside |
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