JPS6227074B2 - - Google Patents

Description

[Detailed description of the invention]

TECHNICAL FIELD The present invention relates to a method for obtaining a compound having laxative action from Senna herbal medicine. Senna herbal medicine consists of dried leaves and legumes of senna plants such as Indian senna (Cassia angustifolia) and Egyptian senna (Cassia acutifolia). The laxative effect of this herbal medicine is 2.
It is based on the following species of compounds: (1) sennosides and (2) non-sennoside laxatives (hereinafter referred to as NSLAS). The laxatives in senna herbal medicine are bimolecular glycoside derivatives of two anthracene compounds rhein and aloe-emodin. Sennoside A, B,
A ₁ , C and D are the most important. Sennosides A, B and A ₁ are bisglycosylleinanthrone, and sennosides C and D are glycosylrein-glycosylaloe-emodindianthrone compounds. In addition to this sennoside, the crude herbal medicine also contains aglycones (sennidine) and other degradation products and derivatives of sennosides. Some of these have a laxative effect, but are also harmful and give undesirable side effects. Side effects typical of senna preparations include nausea, vomiting, flatulence, colic and diarrhea. Various methods have been described in the literature for extracting laxatives from Senna herbal medicine. The most important laxative-active glycosides, such as sennosides A and B, were first isolated from senna herbal medicine by Stoll et al. [Helv.Chim.Acta.XII,
See Fasciculus (1949) p. 1892]. Subsequently, a number of patent documents have been published, which describe the preparation of sennoside concentrates. Traditionally, the production of senna extract is generally carried out in two steps. In the first step, vegetable pigments, fats and other impurities are removed in a suitable solvent such as chloroform, ether (see US Pat. No. 3,089,814) or
90% methanol (German Democratic Republic patent no.
1617667)). After this preliminary extraction, methanol, aqueous methanol,
From this herbal medicine with aqueous ethanol or just water,
Active glycosides are extracted in two steps. To facilitate this extraction, the methanol used can be made alkaline by addition of an organic base (see German Democratic Republic Patent No. 23397). Organic bases form methanol soluble salts with sennosides, which are easily extracted. however,
A disadvantage of this method is that the extract contains large amounts of impurities. By the way, the extraction solvent acidified with citric acid (French Patent No. M6611 (1969) specification) or the extraction solvent acidified with oxalic acid (British Patent No.
832017)) has also been proposed. In the latter case, 70% ethanol was used as the solvent. When acidic methanol or acidic aqueous methanol is used for this extraction, the content of impurities in the extract is lower than when the extraction is carried out using basic solvents or water alone. However, this method requires that the acidic compound sennoside is only slightly soluble in the used solvent as the free acid.
It has the following drawback. Inevitably, the amount of solvent required for this extraction is very large, ~15 to 15% of the weight of the herbal medicine used.
It can be as much as 20 times. For extraction of this herbal medicine, methanol-tetrahydrofuran, methanol-tetrahydrofuran, acidified with phosphoric acid
Dioxane and tetrahydrofuran-dioxane mixtures (see Hung, Teljes 6006 (1973))
It is also known to use phosphoric acid water (see German Democratic Republic Patent No. 1617667) as a solvent. However, since these solvents activate glucosidase enzymes, some of these active glycosides are hydrolyzed, especially when using weak acid solutions, the PH value of which depends on the PH value of the raw material plant. This reduces the amount of active substance in the extract (see German Patent No. 2915063). According to the known literature, sennoside concentrates can be obtained from this extract in various ways. When this extract is dried under mild conditions, a solid sennoside-containing extract is obtained (see German Democratic Republic Patent No. 1617667), which product contains all the substances present in the extract. , the sennoside content of the product is about 17-18%. However, the sennosides can be separated more selectively when they are precipitated from an aqueous solution by addition of an organic solvent. The product obtained is
Contains little ballast material and has a sennoside content of 60-70%. This precipitate is produced by diethyl ether (French Patent No. M611, Magyar G.
et al., Hung. Teljes 6006 (1973)), by addition of isopropyl alcohol (see British Patent No. 832,017) or ethanol (see Finnish Patent No. 41,588) after treatment with a strongly acidic ion exchange resin. . Dissolved sennosides can be converted to calcium salts (see US Pat. No. 3,089,814 and British Patent No. 41,588) and, upon subsequent precipitation by addition of organic solvents, the available glycosides are obtained as calcium salts. It will be done. The content of sennosides in the precipitated product is thus approximately 60-70%. In order to obtain the pure sennoside as the free acid, the sennoside is isolated as a calcium salt and this salt is then decomposed with oxalic acid [Stoll et al., Helv. Chim. Acta XII, Part (1949), p. 1892] reference〕. Thus, according to known methods, extracts and various concentrates containing laxative substances can be obtained from the herbal medicine Senna. The amount of laxative substances in the concentrate depends on the content of these substances in the raw herbal medicine and the method used. One difficulty in standardizing senna formulations is the measurement of senna glycosides. Herbal medicine contains a variety of compounds, including the determination of senna glycosides. However, the physiological effects of these individual compounds are not the same. Therefore, using conventional measurement methods, it is not possible to distinguish senna glycosides from other compounds that have different physiological effects and can therefore cause side effects, and starting from conventional senna extracts It is difficult to obtain formulations that always give the same and reproducible effect at the same dosage. The object of the present invention is to obtain a method for obtaining a laxative substance from the herbal medicine senna in a form as concentrated as possible and with a good yield, as far as possible free of compounds having undesired side effects. Accordingly, the present invention provides a method for obtaining laxative compounds from herbal senna, which comprises: (a) extracting the herbal senna with 70% methanol by countercurrent percolation, and diluting the extract at 50% methanol; Concentrate the extract until complete removal of methanol at a temperature below °C; (b) purify the resulting extract by continuous liquid-liquid extraction with butan-2-ol; The resulting purified concentrate phase (raffinate) is transferred to a crystallizer, acidified with stirring to a pH value of approximately 1.5-2.0, sennoside crystal seeds are introduced, crystallized with stirring, and the resulting crude sennoside crystals are separated. (d) The crude sennoside is then recrystallized, if desired, and optionally (e) 10 parts by weight of the mother liquor from step (c) are added with stirring to 2 parts by weight of sodium chloride. The semi-solid material that aggregates on the surface was decanted, washed and optionally extracted with 95% methanol, the methanol fraction was concentrated and the residue was dried. To carry out the process according to the invention, a mixture of methanol and water is used in which the sennosides are soluble.
The maximum solubility of sennosides is at a methanol concentration of 60-70%, so it is advantageous to use 70% methanol. It is advantageous to carry out the extraction in small volumes and at a slightly elevated temperature, usually at a solvent temperature of +35°C. It is advantageous to avoid high temperatures as there is a risk of decomposition of the sennosides. However, it was surprisingly found that sennosides do not decompose at slightly elevated temperatures when methanol is used as a solvent. The crude drug extraction is carried out by countercurrent percolation method. Generally, 2 to 4 percolators are used. If the extraction solvent is to be heated, it is circulated through an external heat exchanger where it is heated to the desired temperature, but up to 35°C. The more percolators used, the less heating of the solvent should be used. The resulting extract then contains almost no harmful impurities and the sennosides completely crystallize from the mother liquor. Prior to extraction, it is advantageous to swell the dried herbal medicine, and for this purpose it is advantageous to use a leachate (hereinafter referred to as post-leachate) from a previously extracted herbal medicine. For this purpose, the dried herbal medicine is placed in a percolator and covered with a perforated plate having a weight of approximately 0.7 Kg/dm ² , through which the solvent or post-infusion solution is passed. The amount (weight) of solvent required is approximately three times the weight of the dry herbal medicine. It is advantageous to leave it overnight and start the extraction the next day. The extraction is carried out for 16-20 hours, during which time the required amount of 70% methanol is passed through the dry material. The use of several percolators is advantageous, so that when carrying out the extraction, the solvent is first transferred to the percolator with the lowest component concentration of the herbal medicine in the series of percolators, i.e. the one that has already been mostly extracted and then emptied. Pass through the percolator to be processed. The solvent is passed sequentially from this percolator to the next. The main extract is removed from the last liquid-filled percolator. After removing the appropriate amount of extract, a post-infusion solution is obtained which can additionally be used for swelling new batches of dried herbal medicine. For this swelling, the percolator with the lowest component concentration of herbal medicine is emptied, filled with a large amount of herbal medicine, the post-infusion solution is passed through it, and the extraction is carried out the next day. According to the method of the present invention, 1 part of dried herbal medicine can be extracted with 4 parts of extraction solvent. When using 70% methanol at room temperature, the amount of material remaining in the herbal medicine is about 41% per percolator in the series of percolators. When two percolators are used, the extraction yield is (1-0.41 ² ) x 100 = 83%, and when three percolators are used in conjunction, this is (1-0.4 ³ ).
×100=93%. After this extraction, the methanol is substantially quantitatively removed from the leachate, and the amount of bottoms product obtained is about 1/5 of the leachate.
Methanol is removed using a vacuum distillation apparatus equipped with a fractionation column. The temperature should not exceed +50°C as there is a risk of hydrolysis of the sennosides. The resulting concentrate, in addition to the sennosides, also contains all substances that can be extracted with methanol from the raw plant. This concentrate was prepared using butane-2-2-2-2, in order to retain the fat in the concentrate as an emulsion and to act as a preservative to inhibit microbial growth and the resulting spoilage of the solution.
Advantageously, it is mixed with about 5% total. After distilling off the methanol, the concentrate is purified by liquid-liquid extraction using an organic solvent. The solvent used is butan-2-ol. The liquid-liquid extraction is carried out in a continuous manner in a distribution device which theoretically has a separation effect of approximately 10 stages. At this time, the PH value of this feed concentrate solution is approximately 5.4-5.6, and at this PH value the salts of aglycone compounds present in the senna herbal medicine are removed to the extent that the aglycones are actually quantitatively removed from the liquid extract. Hydrolyzed. It is advantageous to saturate the butan-2-ol used for the extraction with water before use. The feed concentrate to be extracted is a very concentrated solution containing approximately 20-30% dry matter. It contains salts, sugars, amino acids and other water-soluble compounds from plants.
This extraction is advantageously carried out in such a way that the butan-2-ol:purification concentrate output ratio is approximately 0.7 to 0.8:1. This liquid-liquid extraction removes fats, harmful plant pigments,
Chlorophylls and carotenoids, free fatty acids, steroids, aglycone anthracene derivatives, neutral glycosides, vegetable waxes and wax alcohols, flavones and other phenols, etc. are removed from this solution. The purified concentrate thus obtained is approximately
The inorganic acids used are preferably hydrochloric acid or It is sulfuric acid. To crystallize the sennosides from the purified concentrate phase, place it in a container and adjust the pH of the solution while stirring.
Pass an amount of acid into it until the value is approximately 1.5-2.0.
Sennoside crystal seeds are then added to this solution and allowed to crystallize for a week or more while stirring. On the other hand, the crystallization can also be carried out in a continuously operated crystallization apparatus. The purified concentrate phase remains in the crystallizer for one week;
It is divided into two or more continuously connected containers which are discharged into a decanter. The crystallization vessel is continuously and gently stirred and for acidification a solution of mineral acid is introduced into the first vessel with stirring. The vertical laminar flow within the vessel is approximately 0.3-0.4 mm/min. This flow rate ensures satisfactory precipitation. Filter the crystalline product, wash with water and methanol or acetone,
Then dry. If desired, the crude product is recrystallized as described below. The fractions of herbal senna that are important with respect to biological effects are those containing non-sennoside laxatives (NSLAS). This fraction appears in variable amounts in crude herbal medicines, extracts and senna preparations. Furthermore, substances of this type are formed during herbal medicine extraction. The laxative effect of the crude NSLAS fraction amounts to approximately 60% of that of the mixture of pure sennosides. However, the toxicity of crude NSLAS fractions applied intravenously is approximately 20 times that of a mixture of pure sennosides. The chemical properties of the NSLAS fraction, its solubility in various solvents, its partitioning properties and its behavior in the case of salt formation are reminiscent of one of the corresponding properties of sennosides. This NSLAS fraction contains the residues of the sennosides remaining in the mother liquor during the crystallization of the purified concentrate phase after the purified extraction with butan-2-ol. The sennoside content of the crude NSLAS fraction amounts to 5-10%. This fraction contains 5-10% of rhein-8 glycosides and 80-90% of compounds whose chemical structure and physiological action are unknown. The crude NSLAS fraction can be separated into two approximately equal large fractions by leaching with 95% methanol. The part that is insoluble in 95% methanol is a brown powder. The chromatogram of this previously unknown compound in gel chromatography appears to be a homogeneous compound, with 1000 ~
It has a retention amount corresponding to a molecular weight of 10,000. 95%
The NSLAS fraction soluble in methanol consists of low molecular weight compounds. This fraction contains approximately 20% sennosides. The main part of this fraction consists of compounds that have not been previously identified in senna herbal medicine or are completely unknown. The crude NSLAS fraction can be easily separated if the sennoside mother liquor is mixed with a salt such as sodium chloride. For this purpose, after filtration of the sennosides, 2 parts by weight of sodium chloride are gradually added to 10 parts of the mother liquor under continuous stirring and stirring is continued for 1 to 2 hours. Subsequently, the semi-solid material that has aggregated on the surface of the solid is decanted from the solution and washed by suspending it in water, the suspension is stirred overnight and the precipitate is allowed to settle out until the next day.
The bulk of the wash solution is then decanted. The precipitate is filtered using a suction filter or using a centrifuge, washed with water and absolute methanol and dried in a stream of air at room temperature. Using senna legume as raw material, the yield of crude NSLAS fraction is:
It is about 1.5-1.6% of the weight of the raw material. Precipitation during salting out can also be carried out from a dilute solution. The crude sennoside obtained after crystallization can be recrystallized if desired. For this purpose, the crude sennosides were suspended in a mixture of acetone and water (50:50) to give a suspension of about 10% and by addition of sodium hydroxide
dissolving with sodium salt formation by bringing the pH value to between 7.5 and 9 and precipitating the sennoside again by adjusting the pH value to approximately 1.5 to 2 with hydrochloric acid;
Separate, wash with aqueous acetone and dry. According to the present invention, the laxative compound contained in the herbal senna drug can be divided into two fractions, namely the sennoside fraction and the NSLAS fraction. The latter fraction is further divided into two
The fractions can be divided into a resin fraction and a low molecular weight fraction. The laxative effect of all fractions reaches about 90% of the total laxative effect of senna herbal medicine. The values for the laxative effect and intravenous toxicity of this fraction (measured in mice) are shown in the following table.

[Table] Thus, using the method of the present invention, sennosides can be obtained with almost 100% purity from crude herbal medicines. Furthermore, the NSLAS crude fraction can also be isolated in concentrated form from the sennoside mother liquor. Additionally, with the method according to the invention for obtaining laxatives from the herbal medicine senna, a preliminary extraction of the herbal medicine is no longer necessary, as is necessary in the case of the hitherto known methods. Since the sennosides obtained by the method of the present invention are fully characterized chemically and pharmacologically,
It can be used to form pharmaceutical compositions with certain galenic properties. In contrast,
According to the methods known up to now, only more or less unspecified galenic extracts are obtained. According to the invention there is also provided a laxative composition comprising at least one laxative compound obtained by the method of the invention in admixture with a solid or liquid pharmaceutical diluent or carrier. can get. The invention is illustrated with reference to the following examples. Example 1 Put 40 kg of senna crude drug into a 250 capacity two-connected percolator and cover it with a perforated steel plate. The solvent used for extraction is 70% methanol, which is applied to the herbal medicine in the first percolator.
A cloth-covered bottom plate is located at the bottom of this percolator. A stop located under this bottom plate is used to pass the solution through the herbal medicine present in the second percolator, with the solvent flowing freely through the first percolator. The flow rate of this solvent is controlled using a stopper attached to the first percolator. The outflow of the second percolator indicates that the level of solvent in the second percolator is
(having a weight of 0.7 Kg/dm ² ). Solvent 160 is used for extraction of 40Kg of senna crude drug. After this amount of 70% methanol passes through both percolators and collects the appropriate amount of leachate,
The outflow pipe of the percolator is connected to the post-leachate container and additionally 70% methanol 60 is passed through the percolator. Thereafter, the remaining solvent is passed from the first percolator to the top of the second percolator, and after-
Collect the leachate until a total of 120 is obtained. Next, empty the first percolator and use the senna herbal medicine again.
40Kg is filled and the post-infusion liquid is pumped over the herbal medicine, the post-infusion liquid 120 is enough to cover the herbal medicine in the infusion. Subsequently, pipes are connected from the outlet to the pump and heat exchanger and from there to the cover of the percolator, and the solution is pumped until the temperature of the solution is +30°C.
Circulate until Then leave it overnight. The next day, this percolator is connected to the previously extracted one and extracted in the manner described above. For each 40 kg of crude drug, 160 leachate is collected, from which methanol is removed in a vacuum rotary evaporator equipped with a packed column. A bottom product of about 30% is obtained,
This was mixed with water-saturated butan-2-ol in a mixer-settler apparatus (10 stages).
Extract using 40. Purified Concentrate Aqueous Phase Approximately 38-40
is obtained, and the butan-2-ol extract is approximately 30-32
is obtained. The purified concentrate aqueous phase is acidified with 93% sulfuric acid with stirring during 20 hours, 1.6% by volume (relative to the amount of liquid to be acidified) is used. The acidified solution then has a PH value of 1.5-2.0. After further stirring for 6 days, the mixture was allowed to settle overnight.
Filter, wash with water until the wash water is colorless, wash with methanol and dry in a stream of air at room temperature. Yield per 40Kg of raw material: Sennoside content 90
~94% and 760-790 g (dry matter). The yield is therefore approximately 70% of the amount of sennosides present in the raw material. 0.5Kg of the crude product was mixed with an acetone-water mixture (1:
1v/v) 5, and add 48% sodium hydroxide to this with stirring until the PH value of the solution reaches
Add until it reaches 8.5-9. Filter out the undissolved residue and add 35% to the solution until the pH value of the solution is 1.5-2.
Add hydrochloric acid. Continue stirring until crystallization begins.
The solution is then allowed to stand for at least 3 hours to crystallize. Filter the precipitate from the solution and add 0.5 ml of water on the strainer.
and wash with acetone 0.5 and dry with a stream of air at room temperature. One-fifth of the mother liquor is mixed with water, washed with acetone, and this solution is used as the crystallization solvent for the next similarly large portion of the crude product. The yield per 0.5 kg of crude product is 98-99% sennoside content,
0.460Kg (dry matter). Example 2 Use the method described in Example 1 using a 3-link percolator and without heating the 70% methanol. Herbal medicine 40
Using 160% solvent per kg, other steps are Example 1
This is the same as the description in . From 40 kg of crude drug, 0.890 kg (dry product) of sennoside crude product with 92% sennoside content is obtained. The crude product is recrystallized as described in Example 1. Example 3 Extraction, removal of methanol from extract and liquid
The liquid extraction is carried out as described in Example 1. After treatment with butan-2-ol, the sennoside mixture is crystallized from the purified concentrate in a continuously operating crystallizer. For this crystallization, two vessels are used which are connected one after the other and a third vessel as a decanter, which is connected to the other. Precipitation of the sennoside mixture is carried out in the latter vessel, with the main amount of precipitate being separated from the mother liquor. For this purpose, the purified concentrate phase obtained after purification with butan-2-ol is first added at a rate of about 2/h.
Pass it through the container. At the same time, add 93% sulfuric acid to the purified concentrate.
Pump into this container an amount of 1.6% by volume. At this point, the liquid in the first vessel is continuously stirred to prevent precipitation. the suspension from the first container is then passed by unrestricted overflow into a second container (also equipped with a stirrer) and from there into a third container by unrestricted overflow; Here, the mother liquor is discharged and precipitated by unlimited overflow.
Drain into waste solvent container. From the third decanter,
The precipitate is removed in the form of a viscous suspension through the stopper provided at the bottom, and the precipitate is filtered through a suction filter.
Wash with water and methanol and dry in a stream of air at room temperature. The yield per 40 kg of raw material used was 790 g with a sennoside content of 91%. Example 4 The mother liquor of Example 1 (obtained after crystallization from the purified concentrate aqueous phase) is treated with sodium chloride. For this purpose, 40 kg of mother liquor (corresponding to 40 kg of the starting material used initially) are gradually mixed with 8 kg of sodium chloride while stirring. In this case, a brown semi-solid precipitate is obtained. Continue stirring for 2 hours and leave the precipitate in this solution until the next day. The mother liquor is then decanted from the precipitate, the precipitate is suspended in 40 ml of water, and the suspension is stirred for 20 hours to allow the precipitate to set out. The precipitate is then filtered using a vacuum filter, washed with copious amounts of water and dried in a stream of air at room temperature, and the dried material is
Pass through a 0.5mm mesh sieve. Yield is 0.60Kg. High pressure liquid chromatography (HPLC) analysis revealed that this precipitate contained approximately 5% sennosides and rhein-
It shows that it contains 5% of 8-glycosides. The laxative effect of this substance is approximately that of sennosides.
It is 58%. Toxicity determined by intravenous administration of
LD ₅₀ = 430 mg/Kg (mouse). This fraction thus contains an unknown compound which on the one hand has a laxative effect but on the other hand has a greater toxicity than the sennosides. The laxative effect of this non-sennoside fraction accounts for approximately 40% of the total laxative effect of the original herbal medicine and crude extract. 48 g of the crude NSLAS fraction is leached 12 times with 500 ml of 95% methanol. For this purpose, the ground powder is mixed with at least 2
Stir for an hour. The methanol wash fractions are collected and evaporated to dryness. The weight of the residue obtained is 22g
It is. Its laxative effect is the same as that of pure sennosides, and its toxicity is LD ₅₀ (intravenous) = 4100
mg/Kg (mouse). Drying the resinous material, which is insoluble in 95% methanol, gives a yield of 20.8 g.
It is. The laxative effect is 10 times higher than that of sennosides.
%, toxicity is LD ₅₀ (intravenous) = 130 mg/Kg. Therefore, the NSLAS fraction isolated from the mother liquor of sennosides by salting out contains a harmless compound with laxative properties of unknown chemical structure that is soluble in 95% methanol, which has only a low laxative effect. and contains highly harmful resinous components of unknown structure. Example 5 The following extraction, liquid-liquid extraction and recrystallization are illustrated with reference to the accompanying figures 1-3. The herbal medicine is extracted in a four-stage countercurrent percolation apparatus at room temperature. For this purpose, senna legumes 40Kg
is continuously introduced into one of four conical containers and loaded with a perforated plate. Pass 70% methanol countercurrently through the four percolator cans in such an amount that the newly introduced legumes are completely covered with liquid. After a soak time of at least 12 hours, percolation is continued until a total of about 160 g of 70% methanol has flowed through. The extract from the container covered with fresh solvent is then passed completely to the next connected container and the extraction residue is dried for solvent recovery. This container can then accept the next 40Kg. The extraction efficiency per percolation step is about 60%. Senna legumes 40 each
From Kg, about 120 of the first extract is obtained, which is
Concentrate under vacuum in a rotary evaporator equipped with a fractionating column to approx. The temperature in the product container must not exceed 50°C. Methanol should be completely removed in order not to interfere with the subsequent liquid-liquid extraction. After gas chromatographic confirmation that the concentrate is methanol-free, about 2% of butan-2-ol is then mixed in. The pH value of this extract is approximately 5.8. For the subsequent liquid-liquid extraction, the concentrate is passed in countercurrent to the butan-2-ol without prior filtration into a 10-stage mixer separator can (approximately 5 stages each). When the inflow ratio of butan-2-ol:extraction concentrate is 1.5:1, the outflow ratio of butan-2-ol extract:purification concentrate is 0.7-0.8:1.
It is. The average residence time for each stage is approximately 20 minutes. The purified concentrate was then adjusted to pH 2 with 94% sulfuric acid, and
Pass through a stage crystallizer. To initiate crystallization, seeds are added and then left to crystallize at room temperature for 5 days. The resulting crystal mud is removed from the bottom of the third crystallization vessel. The collected crystal mud is filtered by suction, and the mother liquor is returned to the crystallization apparatus. It is subsequently washed with water of crystallization and then with methanol and dried at 40° C. in vacuo. Approximately 90% crude sennoside
Obtained with a purity of For recovery of butan-2-ol, complete evaporation of butan-2-ol gives a dark brown to black residue. This distillate is used again for liquid-liquid extraction. The resulting crude sennoside was then suspended in an acetone-water mixture (50/50) to give a 10% suspension, and an aqueous solution of sodium hydroxide was added at a pH of about 7.5.
Complete dissolution is achieved by adding until the sodium salt is formed. The solution is then precipitated again by adjusting the pH value of the solution to 2 with hydrochloric acid. The precipitated product is separated, washed briefly with aqueous acetone and dried. Approximately 2% (based on the senna legume used) of pure sennosides (A and B) is thus obtained.

[Brief explanation of the drawing]

The attached drawings are implementation system diagrams of the method of the present invention. Figure 1 is a diagram showing the extraction step in step (a) of the method of the present invention, and Figure 2 is a diagram showing the extraction process in steps (b) to (c). FIG. 3 is a diagram showing the extraction process, and FIG. 3 is a diagram showing the recrystallization process.

Claims (1)

[Scope of Claims] 1. In order to obtain a laxative compound from the herbal senna drug, (a) the herbal senna drug is processed by countercurrent percolation to 70%
% methanol and the extract is concentrated at a temperature below 50° C. until methanol is completely removed from the extract; Purify by liquid-liquid extraction, (c) Transfer the resulting purified concentrate phase to a crystallizer, acidify with stirring until pH 1.5-2.0, inoculate with sennoside crystal seeds, and stir. (d) the crude sennoside is then recrystallized, if necessary, and optionally (e) 10 parts by weight of the mother liquor from (c). with 2 parts by weight of sodium chloride with stirring, decanting the semi-solid material that aggregates on the surface, washing, and optionally
A method for obtaining a laxative compound from senna herbal medicine, which is characterized by extraction with 95% methanol, concentrating the methanol fraction, and drying the residue. 2. A process according to claim 1, wherein the extraction in step (a) is carried out at an elevated temperature of up to 35°C. 3. A method according to any one of claims 1 to 2, wherein the countercurrent percolation is carried out in 2 to 4 consecutive percolator vessels. 4. The method according to any one of claims 1 to 3, wherein the herbal senna drug is swollen in a post-infusion solution prior to percolation. 5. Add about 5% butane-2- to the concentrate obtained in step (a).
5. The method according to any one of claims 1 to 4, wherein the method is mixed with ol. 6 The organic solvent used was butane-2 saturated with water.
- all. 7. The method of claim 6, wherein the butan-2-ol:purification concentrate effluent ratio is 0.7 to 0.8:1. 8. The method according to any one of claims 1 to 7, wherein the acidification in step (c) is carried out using hydrochloric acid or sulfuric acid. 9 The crude sennoside obtained in step (c) was suspended in an acetone-water mixture (50/50) to give a suspension of about 10% for recrystallization, which was adjusted to pH 7.5~
9 to completely dissolve with the formation of sodium salts, then the sennosides are precipitated again by adjusting the solution to a pH value of about 1.5-2 with hydrochloric acid and washed with aqueous acetone. and drying, claims 1 to 8.
The method described in any one of the preceding paragraphs.