CN101456893B - Method for preparing madecassic acid by hydroxyl asiatic centella glycosides acid hydrolysis - Google Patents
Method for preparing madecassic acid by hydroxyl asiatic centella glycosides acid hydrolysis Download PDFInfo
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Abstract
The invention discloses a method for preparing brahmic acid by acid hydrolysis of madecassoside, which comprises the following steps: 1) adding madecassoside raw material into a mixed solution of an organic solvent I, water and inorganic acid for hydrolysis at a temperature of between 45 and 80 DEG C for 1 to 24 hours; 2) concentrating the hydrolysate solution at reduced pressure to remove the organic solvent I, depositing and filtering the hydrolysate solution to obtain deposit; and 3) drying the deposit, adding the deposit into an organic solvent II 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 yieldand 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 acid 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 staple 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, one big type of more deep component of biological activity research, wherein asiaticoside, Madecassic acid are its important activeconstituentss.
(Madecassoside claims again: O-6-Deoxy-alpha-L-mannopyranosyl-(1.4)-O-beta-D-glucopyranosyl-(1.6)-beta-D-glucopyranosyl (2alpha, 3beta asiaticoside; 4alpha, 6beta)-2,3; 6,23-tetrahydroxyurs-12-en-28-oate, CAS No.: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) is white, needle-shaped crystals, odorless, and 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 distinguished as follows:
The structural formula of the structural formula Madecassic acid of asiaticoside
Research shows, 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 verivates through semi-synthetic; CN1347398 is said like patent, has obtained the verivate of the Madecassic acid salt on 17 carboxyls of part of hydroxyl NSC 166063 E ring, finds the antidepressant effect increase in various degree of these products.In addition; These verivates 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 from Herba Centellae, directly obtains 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 inorganic aqueous acid combines crystallization processes to prepare Madecassic acid.Madecassic acid product yield of the present invention and purity are high, and product can be used as the preparation of bulk drug or Madecassic acid verivate; Simultaneously simple, the required less investment of this method technological process, be easy to realize industriallization.
Summary of the invention
The objective of the invention is to overcome the deficiency of prior art, a kind of method of preparing madecassic acid by hydroxyl asiatic centella glycosides acid hydrolysis is provided.
The step of method is following:
1) in the mixing solutions of organic solvent I, water and mineral acid, adds the asiaticoside raw material, at 45～80 ℃ of following hydrolysis 1～24h;
2) the hydrolyzed solution concentrating under reduced pressure is removed organic solvent I, and post precipitation filters, and gets throw out;
3) the adding organic solvent II was dissolved, is filtered after throw out dried, and filtrating adding water crystallization gets crystallisate after filtering, and crystallisate gets the Madecassic acid product again after vacuum-drying.
Wherein the organic solvent I in the step 1) is methyl alcohol or ethanol, and the volume percent of organic solvent I is 10～90% in the mixing solutions of organic solvent I, water and mineral acid; Mineral acid in the step 1) is hydrochloric acid or sulfuric acid, and the concentration of mineral acid is 0.1～2.0N in the mixing solutions of organic solvent I, water and mineral acid; Hydrolysis temperature in the step 1) is 45～80 ℃, and wherein preferred temperature is 55～78 ℃; Hydrolysis time in the step 1) is 1～24h, and wherein preferable hydrolysis time is 2～15h; Organic solvent II in the step 3) is methyl alcohol or ethanol, and the consumption of organic solvent II is 5～30mL/g throw out (weighing after drying); The consumption of the water in the step 3) is 8～16 times of organic solvent II volume.
The effect of organic solvent I is the solubleness that increases the asiaticoside raw material in the step 1) of the present invention, and the asiaticoside raw material joins in the mixing solutions of organic solvent I, water and mineral acid should form homogeneous phase solution, as if deposition is arranged, need filter out.Hydrolysis reaction and hydrolyzed solution concentrating under reduced pressure are removed to produce in the organic solvent I process to precipitate and are belonged to normal phenomenon.
Madecassic acid product yield of the present invention and purity high (Madecassic acid mass content >=90%), product can be used as the preparation of bulk drug or Madecassic acid verivate; Simultaneously simple, the required less investment of this method technological process, be easy to realize industriallization.
Description of drawings
Accompanying drawing is the process flow diagram of preparing madecassic acid by hydroxyl asiatic centella glycosides acid hydrolysis.
Embodiment
Asiaticoside raw material used in the present invention is 90.1% available from the natural pharmaceutcal corporation, Ltd of Guangxi Chang Zhou through the mass content that detects asiaticoside.
Asiaticoside and Madecassic acid content adopt HPLC (HPLC) to measure, and adopt external standard method quantitative.Adopt Agilent1100 liquid-phase chromatographic analysis system, analysis condition is following: and Eclipse XDB-C18 reversed-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 1HPLC method is measured the eluent gradient of asiaticoside and Madecassic acid
Below with embodiment process method of the present invention is further described.Protection scope of the present invention does not receive the restriction of embodiment, and protection scope of the present invention is determined by claims.
The calculation formula of yield is following 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 methyl alcohol, water and vitriolic mixing solutions 500mL, wherein the volume percent of methyl alcohol is 10%, and vitriolic equivalent concentration is 0.1N; There-necked flask is put into 65 ℃ water bath with thermostatic control, opens and stirs and water of condensation, adds 10g asiaticoside raw material, hydrolysis 24h; The hydrolyzed solution concentrating under reduced pressure is removed methyl alcohol, and post precipitation filters, throw out, weigh after throw out dries 4.7g; Throw out after collection is dried adds 23.5mL dissolve with methanol, filtration; Filtrating adds the 423mL water crystallization, gets crystallisate after filtering, and crystallisate gets 3.3g Madecassic acid product again after vacuum-drying; Product is through the mass content 85.9% of HPLC analysis Madecassic acid, yield 60.8%.
Embodiment 2
In the there-necked flask of stirring of 1L band and water condensing tube, add the mixing solutions 500mL of methyl alcohol, water and hydrochloric acid, wherein the volume percent of methyl alcohol is 20%, and the equivalent concentration of hydrochloric acid is 0.5N; There-necked flask is put into 65 ℃ water bath with thermostatic control, opens and stirs and water of condensation, adds 20g asiaticoside raw material, hydrolysis 10h; The hydrolyzed solution concentrating under reduced pressure is removed methyl alcohol, and post precipitation filters, throw out, weigh after throw out dries 9.3g; Throw out after collection is dried adds 93mL dissolve with ethanol, filtration; Filtrating adds the 1488mL water crystallization, gets crystallisate after filtering, and crystallisate gets 6.7g Madecassic acid product again after vacuum-drying; Product is through the mass content 90.6% of HPLC analysis Madecassic acid, yield 65.1%.
Embodiment 3
In the there-necked flask of stirring of 1L band and water condensing tube, add methyl alcohol, water and vitriolic mixing solutions 500mL, wherein the volume percent of methyl alcohol is 30%, and vitriolic equivalent concentration is 1.0N; There-necked flask is put into 60 ℃ water bath with thermostatic control, opens and stirs and water of condensation, adds 30g asiaticoside raw material, hydrolysis 8h; The hydrolyzed solution concentrating under reduced pressure is removed methyl alcohol, and post precipitation filters, throw out, weigh after throw out dries 14.0g; Throw out after collection is dried adds 210mL dissolve with ethanol, filtration; Filtrating adds the 2940mL water crystallization, gets crystallisate after filtering, and crystallisate gets 9.9g Madecassic acid product again after vacuum-drying; Product is through the mass content 91.0% of HPLC analysis Madecassic acid, yield 64.4%.
Embodiment 4
In the there-necked flask of stirring of 1L band and water condensing tube, add the mixing solutions 500mL of methyl alcohol, water and hydrochloric acid, wherein the volume percent of methyl alcohol is 40%, and the equivalent concentration of hydrochloric acid is 1.5N; There-necked flask is put into 60 ℃ water bath with thermostatic control, opens and stirs and water of condensation, adds 40g asiaticoside raw material, hydrolysis 6h; The hydrolyzed solution concentrating under reduced pressure is removed methyl alcohol, and post precipitation filters, throw out, weigh after throw out dries 18.6g; Throw out after collection is dried adds 372mL dissolve with methanol, filtration; Filtrating adds the 4464mL water crystallization, gets crystallisate after filtering, and crystallisate gets 13.0g Madecassic acid product again after vacuum-drying; Product is through the mass content 91.2% of HPLC analysis Madecassic acid, yield 63.6%.
Embodiment 5
In the there-necked flask of stirring of 1L band and water condensing tube, add methyl alcohol, water and vitriolic mixing solutions 500mL, wherein the volume percent of methyl alcohol is 50%, and vitriolic equivalent concentration is 2.0N; There-necked flask is put into 55 ℃ water bath with thermostatic control, opens and stirs and water of condensation, adds 50g asiaticoside raw material, hydrolysis 9h; The hydrolyzed solution concentrating under reduced pressure is removed methyl alcohol, and post precipitation filters, throw out, weigh after throw out dries 23.2g; Throw out after collection is dried adds 580mL dissolve with methanol, filtration; Filtrating adds the 5800mL water crystallization, gets crystallisate after filtering, and crystallisate gets 15.9g Madecassic acid product again after vacuum-drying; Product is through the mass content 90.2% of HPLC analysis Madecassic acid, yield 61.5%.
Embodiment 6
In the there-necked flask of stirring of 1L band and water condensing tube, add the mixing solutions 500mL of methyl alcohol, water and hydrochloric acid, wherein the volume percent of methyl alcohol is 60%, and the equivalent concentration of hydrochloric acid is 2.0N; There-necked flask is put into 55 ℃ water bath with thermostatic control, opens and stirs and water of condensation, adds 20g asiaticoside raw material, hydrolysis 12h; The hydrolyzed solution concentrating under reduced pressure is removed methyl alcohol, and post precipitation filters, throw out, weigh after throw out dries 9.3g; Throw out after collection is dried adds 279mL dissolve with ethanol, filtration; Filtrating adds the 2232mL water crystallization, gets crystallisate after filtering, and crystallisate gets 6.2g Madecassic acid product again after vacuum-drying; Product is through the mass content 90.5% of HPLC analysis Madecassic acid, yield 60.2%.
Embodiment 7
In the there-necked flask of stirring of 1L band and water condensing tube, add methyl alcohol, water and vitriolic mixing solutions 500mL, wherein the volume percent of methyl alcohol is 70%, and vitriolic equivalent concentration is 1.6N; There-necked flask is put into 50 ℃ water bath with thermostatic control, opens and stirs and water of condensation, adds 30g asiaticoside raw material, hydrolysis 18h; The hydrolyzed solution concentrating under reduced pressure is removed methyl alcohol, and post precipitation filters, throw out, weigh after throw out dries 14.2g; Throw out after collection is dried adds 142mL dissolve with ethanol, filtration; Filtrating adds the 2272mL water crystallization, gets crystallisate after filtering, and crystallisate gets 10.2g Madecassic acid product again after vacuum-drying; Product is through the mass content 90.3% of HPLC analysis Madecassic acid, yield 65.8%.
Embodiment 8
In the there-necked flask of stirring of 1L band and water condensing tube, add the mixing solutions 500mL of methyl alcohol, water and hydrochloric acid, wherein the volume percent of methyl alcohol is 80%, and the equivalent concentration of hydrochloric acid is 1.2N; There-necked flask is put into 50 ℃ water bath with thermostatic control, opens and stirs and water of condensation, adds 40g asiaticoside raw material, hydrolysis 20h; The hydrolyzed solution concentrating under reduced pressure is removed methyl alcohol, and post precipitation filters, throw out, weigh after throw out dries 18.9g; Throw out after collection is dried adds 283.5mL dissolve with methanol, filtration; Filtrating adds the 3969mL water crystallization; Get crystallisate after filtering; Crystallisate gets 13.2g Madecassic acid product again after vacuum-drying, product is through the mass content 90.1% of HPLC analysis Madecassic acid, yield 63.8%.
Embodiment 9
In the there-necked flask of stirring of 1L band and water condensing tube, add methyl alcohol, water and vitriolic mixing solutions 500mL, wherein the volume percent of methyl alcohol is 90%, and vitriolic equivalent concentration is 0.8N; There-necked flask is put into 45 ℃ water bath with thermostatic control, opens and stirs and water of condensation, adds 20g asiaticoside raw material, hydrolysis 24h; The hydrolyzed solution concentrating under reduced pressure is removed methyl alcohol, and post precipitation filters, throw out, weigh after throw out dries 9.6g; Throw out after collection is dried adds 192mL dissolve with methanol, filtration; Filtrating adds the 2304mL water crystallization, gets crystallisate after filtering, and crystallisate gets 7.0g Madecassic acid product again after vacuum-drying; Product is through the mass content 82.4% of HPLC analysis Madecassic acid, yield 61.8%.
Embodiment 10
In the there-necked flask of stirring of 1L band and water condensing tube, add methyl alcohol, water and vitriolic mixing solutions 500mL, wherein the volume percent of methyl alcohol is 20%, and vitriolic equivalent concentration is 0.6N; There-necked flask is put into 65 ℃ water bath with thermostatic control, opens and stirs and water of condensation, adds 30g asiaticoside raw material, hydrolysis 8h; The hydrolyzed solution concentrating under reduced pressure is removed methyl alcohol, and post precipitation filters, throw out, weigh after throw out dries 13.9g; Throw out after collection is dried adds 347.5mL dissolve with ethanol, filtration; Filtrating adds the 3475mL water crystallization; Get crystallisate after filtering; Crystallisate gets 9.2g Madecassic acid product again after vacuum-drying, product is through the mass content 91.2% of HPLC analysis Madecassic acid, yield 60.0%.
Embodiment 11
In the there-necked flask of stirring of 1L band and water condensing tube, add methyl alcohol, water and vitriolic mixing solutions 500mL, wherein the volume percent of methyl alcohol is 40%, and vitriolic equivalent concentration is 0.2N; There-necked flask is put into 65 ℃ water bath with thermostatic control, opens and stirs and water of condensation, adds 40g asiaticoside raw material, hydrolysis 9h; The hydrolyzed solution concentrating under reduced pressure is removed methyl alcohol, and post precipitation filters, throw out, weigh after throw out dries 18.5g; Throw out after collection is dried adds 185mL dissolve with ethanol, filtration; Filtrating adds the 2960mL water crystallization, gets crystallisate after filtering, and crystallisate gets 13.5g Madecassic acid product again after vacuum-drying; Product is through the mass content 90.9% of HPLC analysis Madecassic acid, yield 65.8%.
Embodiment 12
In the there-necked flask of stirring of 1L band and water condensing tube, add methyl alcohol, water and vitriolic mixing solutions 500mL, wherein the volume percent of methyl alcohol is 60%, and vitriolic equivalent concentration is 0.4N; There-necked flask is put into 60 ℃ water bath with thermostatic control, opens and stirs and water of condensation, adds 25g asiaticoside raw material, hydrolysis 10h; The hydrolyzed solution concentrating under reduced pressure is removed methyl alcohol, and post precipitation filters, throw out, weigh after throw out dries 11.4g; Throw out after collection is dried adds 171mL dissolve with methanol, filtration; Filtrating adds the 2394mL water crystallization, gets crystallisate after filtering, and crystallisate gets 8.3g Madecassic acid product again after vacuum-drying; Product is through the mass content 90.7% of HPLC analysis Madecassic acid, yield 64.6%.
Embodiment 13
In the there-necked flask of stirring of 1L band and water condensing tube, add methyl alcohol, water and vitriolic mixing solutions 500mL, wherein the volume percent of methyl alcohol is 80%, and vitriolic equivalent concentration is 1.0N; There-necked flask is put into 60 ℃ water bath with thermostatic control, opens and stirs and water of condensation, adds 35g asiaticoside raw material, hydrolysis 9h; The hydrolyzed solution concentrating under reduced pressure is removed methyl alcohol, and post precipitation filters, throw out, weigh after throw out dries 16.1g; Throw out after collection is dried adds 322mL dissolve with methanol, filtration; Filtrating adds the 3864mL water crystallization, gets crystallisate after filtering, and crystallisate gets 11.4g Madecassic acid product again after vacuum-drying; Product is through the mass content 91.3% of HPLC analysis Madecassic acid, yield 63.8%.
Embodiment 14
In the there-necked flask of stirring of 1L band and water condensing tube, add ethanol, water and vitriolic mixing solutions 500mL, wherein the alcoholic acid volume percent is 10%, and vitriolic equivalent concentration is 0.1N; There-necked flask is put into 80 ℃ water bath with thermostatic control, opens and stirs and water of condensation, adds 10g asiaticoside raw material, hydrolysis 14h; The hydrolyzed solution concentrating under reduced pressure is removed ethanol, and post precipitation filters, throw out, weigh after throw out dries 4.8g; Throw out after collection is dried adds 24mL dissolve with ethanol, filtration; Filtrating adds the 432mL water crystallization, gets crystallisate after filtering, and crystallisate gets 3.5g Madecassic acid product again after vacuum-drying; Product is through the mass content 86.3% of HPLC analysis Madecassic acid, yield 64.8%.
Embodiment 15
In the there-necked flask of stirring of 1L band and water condensing tube, add the mixing solutions 500mL of ethanol, water and hydrochloric acid, wherein the alcoholic acid volume percent is 20%, and the equivalent concentration of hydrochloric acid is 0.5N; There-necked flask is put into 75 ℃ water bath with thermostatic control, opens and stirs and water of condensation, adds 20g asiaticoside raw material, hydrolysis 5h; The hydrolyzed solution concentrating under reduced pressure is removed ethanol, and post precipitation filters, throw out, weigh after throw out dries 9.1g; Throw out after collection is dried adds 91mL dissolve with ethanol, filtration; Filtrating adds the 1456mL water crystallization, gets crystallisate after filtering, and crystallisate gets 6.7g Madecassic acid product again after vacuum-drying; Product is through the mass content 90.7% of HPLC analysis Madecassic acid, yield 65.2%.
Embodiment 16
In the there-necked flask of stirring of 1L band and water condensing tube, add ethanol, water and vitriolic mixing solutions 500mL, wherein the alcoholic acid volume percent is 30%, and vitriolic equivalent concentration is 1.0N; There-necked flask is put into 70 ℃ water bath with thermostatic control, opens and stirs and water of condensation, adds 30g asiaticoside raw material, hydrolysis 4h; The hydrolyzed solution concentrating under reduced pressure is removed ethanol, and post precipitation filters, throw out, weigh after throw out dries 13.8g; Throw out after collection is dried adds 207mL dissolve with methanol, filtration; Filtrating adds the 2898mL water crystallization, gets crystallisate after filtering, and crystallisate gets 9.9g Madecassic acid product again after vacuum-drying; Product is through the mass content 91.1% of HPLC analysis Madecassic acid, yield 64.5%.
Embodiment 17
In the there-necked flask of stirring of 1L band and water condensing tube, add the mixing solutions 500mL of ethanol, water and hydrochloric acid, wherein the alcoholic acid volume percent is 40%, and the equivalent concentration of hydrochloric acid is 1.5N; There-necked flask is put into 65 ℃ water bath with thermostatic control, opens and stirs and water of condensation, adds 40g asiaticoside raw material, hydrolysis 5h; The hydrolyzed solution concentrating under reduced pressure is removed ethanol, and post precipitation filters, throw out, weigh after throw out dries 18.5g; Throw out after collection is dried adds 370mL dissolve with methanol, filtration; Filtrating adds the 4440mL water crystallization, gets crystallisate after filtering, and crystallisate gets 12.9g Madecassic acid product again after vacuum-drying; Product is through the mass content 91.4% of HPLC analysis Madecassic acid, yield 63.2%.
Embodiment 18
In the there-necked flask of stirring of 1L band and water condensing tube, add ethanol, water and vitriolic mixing solutions 500mL, wherein the alcoholic acid volume percent is 50%, and vitriolic equivalent concentration is 2.0N; There-necked flask is put into 65 ℃ water bath with thermostatic control, opens and stirs and water of condensation, adds 50g asiaticoside raw material, hydrolysis 5h; The hydrolyzed solution concentrating under reduced pressure is removed ethanol, and post precipitation filters, throw out, weigh after throw out dries 23.0g; Throw out after collection is dried adds 575mL dissolve with ethanol, filtration; Filtrating adds the 5750mL water crystallization, gets crystallisate after filtering, and crystallisate gets 15.4g Madecassic acid product again after vacuum-drying; Product is through the mass content 90.8% of HPLC analysis Madecassic acid, yield 60.0%.
Embodiment 19
In the there-necked flask of stirring of 1L band and water condensing tube, add the mixing solutions 500mL of ethanol, water and hydrochloric acid, wherein the alcoholic acid volume percent is 60%, and the equivalent concentration of hydrochloric acid is 2.0N; There-necked flask is put into 60 ℃ water bath with thermostatic control, opens and stirs and water of condensation, adds 20g asiaticoside raw material, hydrolysis 7h; The hydrolyzed solution concentrating under reduced pressure is removed ethanol, and post precipitation filters, throw out, weigh after throw out dries 9.0g; Throw out after collection is dried adds 270mL dissolve with ethanol, filtration; Filtrating adds the 2160mL water crystallization, gets crystallisate after filtering, and crystallisate gets 6.0g Madecassic acid product again after vacuum-drying; Product is through the mass content 90.2% of HPLC analysis Madecassic acid, yield 58.0%.
Embodiment 20
In the there-necked flask of stirring of 1L band and water condensing tube, add ethanol, water and vitriolic mixing solutions 500mL, wherein the alcoholic acid volume percent is 70%, and vitriolic equivalent concentration is 1.6N; There-necked flask is put into 55 ℃ water bath with thermostatic control, opens and stirs and water of condensation, adds 30g asiaticoside raw material, hydrolysis 12h; The hydrolyzed solution concentrating under reduced pressure is removed ethanol, and post precipitation filters, throw out, weigh after throw out dries 13.9g; Throw out after collection is dried adds 139mL dissolve with methanol, filtration; Filtrating adds the 2224mL water crystallization, gets crystallisate after filtering, and crystallisate gets 10.1g Madecassic acid product again after vacuum-drying; Product is through the mass content 90.4% of HPLC analysis Madecassic acid, yield 65.3%.
Embodiment 21
In the there-necked flask of stirring of 1L band and water condensing tube, add the mixing solutions 500mL of ethanol, water and hydrochloric acid, wherein the alcoholic acid volume percent is 80%, and the equivalent concentration of hydrochloric acid is 1.2N; There-necked flask is put into 50 ℃ water bath with thermostatic control, opens and stirs and water of condensation, adds 40g asiaticoside raw material, hydrolysis 18h; The hydrolyzed solution concentrating under reduced pressure is removed ethanol, and post precipitation filters, throw out, weigh after throw out dries 18.7g; Throw out after collection is dried adds 280.5mL dissolve with methanol, filtration; Filtrating adds the 3927mL water crystallization; Get crystallisate after filtering; Crystallisate gets 13.5g Madecassic acid product again after vacuum-drying, product is through the mass content 89.7% of HPLC analysis Madecassic acid, yield 64.9%.
Embodiment 22
In the there-necked flask of stirring of 1L band and water condensing tube, add ethanol, water and vitriolic mixing solutions 500mL, wherein the alcoholic acid volume percent is 90%, and vitriolic equivalent concentration is 0.8N; There-necked flask is put into 45 ℃ water bath with thermostatic control, opens and stirs and water of condensation, adds 20g asiaticoside raw material, hydrolysis 24h; The hydrolyzed solution concentrating under reduced pressure is removed ethanol, and post precipitation filters, throw out, weigh after throw out dries 9.6g; Throw out after collection is dried adds 192mL dissolve with ethanol, filtration; Filtrating adds the 2304mL water crystallization, gets crystallisate after filtering, and crystallisate gets 7.0g Madecassic acid product again after vacuum-drying; Product is through the mass content 84.2% of HPLC analysis Madecassic acid, yield 63.2%.
Embodiment 23
In the there-necked flask of stirring of 1L band and water condensing tube, add ethanol, water and vitriolic mixing solutions 500mL, wherein the alcoholic acid volume percent is 20%, and vitriolic equivalent concentration is 0.6N; There-necked flask is put into 80 ℃ water bath with thermostatic control, opens and stirs and water of condensation, adds 30g asiaticoside raw material, hydrolysis 3h; The hydrolyzed solution concentrating under reduced pressure is removed ethanol, and post precipitation filters, throw out, weigh after throw out dries 13.7g; Throw out after collection is dried adds 342.5mL dissolve with ethanol, filtration; Filtrating adds the 3425mL water crystallization; Get crystallisate after filtering; Crystallisate gets 9.4g Madecassic acid product again after vacuum-drying, product is through the mass content 92.1% of HPLC analysis Madecassic acid, yield 61.9%.
Embodiment 24
In the there-necked flask of stirring of 1L band and water condensing tube, add ethanol, water and vitriolic mixing solutions 500mL, wherein the alcoholic acid volume percent is 40%, and vitriolic equivalent concentration is 0.2N; There-necked flask is put into 70 ℃ water bath with thermostatic control, opens and stirs and water of condensation, adds 40g asiaticoside raw material, hydrolysis 8h; The hydrolyzed solution concentrating under reduced pressure is removed ethanol, and post precipitation filters, throw out, weigh after throw out dries 18.5g; Throw out after collection is dried adds 185mL dissolve with methanol, filtration; Filtrating adds the 2960mL water crystallization, gets crystallisate after filtering, and crystallisate gets 13.2g Madecassic acid product again after vacuum-drying; Product is through the mass content 91.4% of HPLC analysis Madecassic acid, yield 64.7%.
Embodiment 25
In the there-necked flask of stirring of 1L band and water condensing tube, add ethanol, water and vitriolic mixing solutions 500mL, wherein the alcoholic acid volume percent is 60%, and vitriolic equivalent concentration is 0.4N; There-necked flask is put into 65 ℃ water bath with thermostatic control, opens and stirs and water of condensation, adds 25g asiaticoside raw material, hydrolysis 8h; The hydrolyzed solution concentrating under reduced pressure is removed ethanol, and post precipitation filters, throw out, weigh after throw out dries 11.5g; Throw out after collection is dried adds 172.5mL dissolve with methanol, filtration; Filtrating adds the 2415mL water crystallization; Get crystallisate after filtering; Crystallisate gets 7.8g Madecassic acid product again after vacuum-drying, product is through the mass content 91.6% of HPLC analysis Madecassic acid, yield 61.3%.
Embodiment 26
In the there-necked flask of stirring of 1L band and water condensing tube, add ethanol, water and vitriolic mixing solutions 500mL, wherein the alcoholic acid volume percent is 80%, and vitriolic equivalent concentration is 1.0N; There-necked flask is put into 55 ℃ water bath with thermostatic control, opens and stirs and water of condensation, adds 35g asiaticoside raw material, hydrolysis 14h; The hydrolyzed solution concentrating under reduced pressure is removed ethanol, and post precipitation filters, throw out, weigh after throw out dries 16.1g; Throw out after collection is dried adds 322mL dissolve with ethanol, filtration; Filtrating adds the 3864mL water crystallization, gets crystallisate after filtering, and crystallisate gets 10.8g Madecassic acid product again after vacuum-drying; Product is through the mass content 91.4% of HPLC analysis Madecassic acid, yield 60.5%.
Embodiment 27
In the there-necked flask of stirring of 1L band and water condensing tube, add ethanol, water and vitriolic mixing solutions 500mL, wherein the alcoholic acid volume percent is 10%, and vitriolic equivalent concentration is 2.0N; There-necked flask is put into 80 ℃ water bath with thermostatic control, opens and stirs and water of condensation, adds 15g asiaticoside raw material, hydrolysis 1h; The hydrolyzed solution concentrating under reduced pressure is removed ethanol, and post precipitation filters, throw out, weigh after throw out dries 6.9g; Throw out after collection is dried adds 172.5mL dissolve with methanol, filtration; Filtrating adds the 2415mL water crystallization; Get crystallisate after filtering; Crystallisate gets 4.3g Madecassic acid product again after vacuum-drying, product is through the mass content 90.1% of HPLC analysis Madecassic acid, yield 55.4%.
Claims (3)
1. the method for a preparing madecassic acid by hydroxyl asiatic centella glycosides acid hydrolysis is characterized in that, the step of method is following:
1) in the mixing solutions of organic solvent I, water and mineral acid, adds the asiaticoside raw material, at 45～80 ℃ of following hydrolysis 1～24h;
2) the hydrolyzed solution concentrating under reduced pressure is removed organic solvent I, and post precipitation filters, and gets throw out;
3) the adding organic solvent II was dissolved, is filtered after throw out dried, and filtrating adding water crystallization gets crystallisate after filtering, and crystallisate gets the Madecassic acid product again after vacuum-drying;
The described organic solvent I of step 1) is methyl alcohol or ethanol; The volume percent of the organic solvent I in the mixing solutions of step 1) organic solvent I, water and mineral acid is 10～90%; Mineral acid in the step 1) is hydrochloric acid or sulfuric acid; The concentration of mineral acid is 0.1～2.0N in the mixing solutions of step 1) organic solvent I, water and mineral acid; Organic solvent II in the step 3) is methyl alcohol or ethanol, and the consumption of organic solvent II is 5～30mL/g throw out in the step 3), and the consumption of water is 8～16 times of organic solvent II volume in the step 3).
2. the method for a kind of preparing madecassic acid by hydroxyl asiatic centella glycosides acid hydrolysis according to claim 1 is characterized in that the hydrolysis temperature in the step 1) is 55～78 ℃.
3. the method for a kind of preparing madecassic acid by hydroxyl asiatic centella glycosides acid hydrolysis according to claim 1 is characterized in that the hydrolysis time in the step 1) is 2～15h.
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| US3551408A (en) * | 1966-08-08 | 1970-12-29 | Lab Laroche Navarron | Triterpene derivatives,process for preparing same,and applications thereof |
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| US3551408A (en) * | 1966-08-08 | 1970-12-29 | Lab Laroche Navarron | Triterpene derivatives,process for preparing same,and applications thereof |
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