KR880000018B1 - Process for obtaining laxative compounds from senna drug - Google Patents

Abstract

Sennosides was extd. from senna by percolation with 70% MeOH, the ext. was concd. at<= 50≰C and extd. with H2O-satd. 2-BuOH. The aq. phase is stirred with H2SO4 (pH 1.5-2.0) for 6 days, and the ppt. was filtered, washed with H2O and then MeOH. The yield was 760-790g with a sennoside content of 90-94%. The purity was increased to 98-99% by dissolving in 50% aq. Me2CO at pH 8.5-9.0, filtering, adjusting to pH 1.5-2.0, and separating the crystals formed.

Description

Process for preparing laxatives from senna

1 is a flow chart of the extraction process of the present invention.

2 is a flow chart of the liquid-liquid extraction process of the present invention.

3 is a flow chart of the recrystallization process of the present invention.

The present invention relates to a process for preparing a laxative from Senna drug.

Senna medicaments consist of senna leaves and pods. Senna plants include the Indian senna (Cassia anguststifolia) and the Egyptian senna (Cassia actifolia). The laxative action of senna drugs is caused by two kinds of compounds contained, namely sennosides and vicenoside laxatives (hereinafter referred to as NSLAS).

The laxative agent in the senna drug is a bimolecular glycoside derivative of two anthracene compounds, rhein and aloe-emodin. The most important are Senosides A, B, A ₁ , C and D. Sennosides A, B and A ₁ are bis-glucosylline antrons and sennosides C and D are glycosylline-glycosylaloe-emodin dianthrone compounds.

In addition to sennosides, the herbal medicine contains aglucon (sennidine) and other sennoside derivatives and degradation products. Some of them have a laxative effect, but at the same time they are toxic and cause side effects. Representative side effects include nausea, vomiting, wind, abdominal pain and diarrhea.

Several processes have been published to extract laxative substances from senna. The most important laxative glucosides (Sennosides A and B) were first isolated from Senna et al. By Stoll et al. (Helv, Chim, Acta.XXXII, Fasciculus VI (1949), 1892). In addition, many patent publications have been issued on the preparation of sennoside concentrates.

So far, the senna extraction method has been performed in two stages. In the first step, plant pigments, fats and other impurities are removed with a suitable solvent such as chloroform, ether (see US Pat. No. 3,089,814), or 90% methanol (see German Patent Publication No. 16 17 667). After this primary extraction, as a second step, active glucosides are extracted with methanol, aqueous methanol, aqueous ethanol or water alone.

In order to facilitate extraction, the used methanol is alkalized by adding an organic base (cf. German Patent Publication No. 23 397). Organic bases produce methanol dissolved salts that can be easily extracted with the sennosides. However, the disadvantage of this process is the high impurity content in the extract.

In addition, it has been proposed to use extraction solvents which have been acidified with citric acid (see French Patent Publication No. M 6611 (1969)) or with fisheries (see British Patent Publication 832, 017). In the latter case, 70% ethanol was used as the solvent. When acidic methanol or acidic aqueous methanol solution is used for extraction, the impurity content in the extract is reduced compared to that obtained using only basic solvent or water. However, this process also has the drawback that the acidic senosides are sometimes present as free acids that are almost insoluble in the solvent used. Therefore, the amount of solvent required for extraction must be large, and as a result, it can be as large as 15-20 times the weight of the raw material pharmaceutical. In the extraction of the drug, methanol-tetrahydrofuran, methanol-dioxane and acidified with phosphoric acid (Hung. Teljes. 6006 (1973)) and aqueous phosphoric acid solution (see German Patent Publication No. 16 17 667); It is known to use a mixture of tetrahydrofuran-dioxane as a solvent. However, these solvents activate glucosidase enzymes to hydrolyze some of the active glucosides (especially when using weakly acidic solutions) to have a pH value corresponding to the raw material. This reduces the amount of active substance in the extract (cf. German Patent Publication No. 29 15 063).

According to the prior art, the sennoside concentrate is produced by various methods.

Solid, sennoside-containing extracts are obtained by slowly drying the extract (see, for example, Federal Patent Application No. 16 17 667). The product thus obtained contains all the substances in the extract with a sennoside content of about 17-18%.

However, sennoside can be separated more selectively by adding an organic solvent and precipitating from the aqueous solution. The material thus obtained contains a small amount of stabilizer and has a senoside content of 60-70%. Precipitation was carried out by adding diethyl ether (see French Patent Publication M611: Magyar G. et al., Hung Teljes, 6006 (1973) and isopropyl alcohol, followed by strong acid ionic crosslinking resin (Reference: British Patent Publication 832,017) or ethanol ( Reference: this is carried out by the treatment of FILAND 41588. Senosides in the solution are converted to calcium salts (see US Patent 3,089,814 Finland 41588) and subsequently precipitated by adding an organic solvent to activate the glucoside into the calcium salt. The sennoside content in the precipitate is 60-70%.

In order to obtain pure senosides as free acids, sennosides, which are called calcium salts, are decomposed into fisheries (Stoll et al., Helv. Chim. Acta. XXXII, Fasciculus VI (1949), 1892).

According to the process known above, it can be seen that various concentrates and extracts containing substances with laxative action can be prepared in Senna Pharmaceuticals. The amount of laxative substance in the concentrate depends on the content of the substance in the original drug substance and the manufacturing process used. One difficult problem in standardizing the senna manufacturing process is measuring senna glycosides. The drug contains various compounds involved in the determination of senna glycosides. However, the physiological action of each of these substances is not the same. It is not possible to distinguish senna glycosides from compounds that have different physiological actions and potential side effects by commercial measurement methods. It is difficult to produce a substance that always acts the same reproducible capacity.

One of the objectives of the present invention is to develop a process for obtaining laxatives from senna pharmaceuticals that provide a laxative substance, providing the process in the most concentrated form possible so that the yield is improved and the components causing unwanted side effects are removed. will be.

In the present invention, the process of obtaining a laxative from senna medicament consists of the following steps:

a) Senna Pharmaceuticals is extracted with aqueous methanol by countercurrent osmosis and concentrated at a temperature below 50 ° C. until methanol is completely removed;

b) the extract is purified by continuous liquid-liquid extraction with an organic solvent;

c) Transfer the purified material (raffinide raffinate) to the crystallization apparatus, acidify until the pH is about 1.5 to 2.0 while stirring, seeding by adding sennoside crystals, continue stirring and continue crystallization After separating the produced crystalline crude sennoside;

d) re-determination of Joe Sennoside, if necessary;

e) 10 parts by weight of the mother liquor of step (c) were stirred and mixed with 2 parts by weight of sodium chloride (2 parts by weight) to remove the semi-solid coagulum on the surface by decantation and washing, followed by extraction with 95% methanol and concentration of this. Then dry.

In carrying out the process of the present invention a mixture of methanol and water is used when the sennoside is soluble. It is preferable to use 70% methanol because the maximum solubility of sennoside in methanol is between 60-70% methanol concentration. The extraction is done in portions and slightly warmed up, but the maximum temperature is + 35 ° C. High temperatures should be avoided as sennosides may decompose. However, when methanol was used as a solvent, it was surprising that even though the temperature was slightly increased, the sennosides did not decompose.

Reflux osmosis is used for drug extraction. As a rule, 2-4 osmosis machines are used. When the extraction solvent is warmed, it is allowed to be purified through an external heat exchanger which is heated to a temperature of up to 35 ° C. The more you use the osmosis, the less warm the solvent. The extract thus obtained contains less harmful impurities and sennoside is completely crystallized from the mother liquor.

Before extraction, it is better to call the dry agent in the solvent, since it is preferable to use post-osmosis from the previously extracted drug. For this purpose, the drying agent is placed in an osmosis machine and covered with a porous plate weighing about 0.7 kg / dm 2 to allow passage of solvent or post-osmosis. The weight of the solvent required is about three times the weight of the dry drug. The dry agent is preferably left overnight in the solvent and then extracted the next day.

The extraction time is over 16-20 hours, during which time the required amount of 70% methanol is allowed to flow through the dry matter. It is preferable to use 5-6 osmosis machines, so during extraction the solvent is first passed through successive osmosis machines. At this time, the weakest drug is put in the osmosis, which is almost extracted from one place and the next is empty. The solvent that has passed through this osmosis passes through the next osmosis and this step proceeds. Master extract is received in the very last osmosis. After the appropriate amount of extract has been removed, in addition, after osmosis is obtained which can be used to call a new batch of dry medicament. For some purpose, the osmotic machine containing the lowest drug content is emptied, the drug is filled, the osmotic material passes and the extraction is carried out the next day.

According to the process of the present invention, only 1 part of the drying agent can be extracted with only 4 parts of the extraction solvent. If 70% methanol is used at ambient temperature, the remaining amount in the drug is about 41% per osmotic phase. The extraction yield is (1-0.41 ² ) × 100 = 83% if two osmosis machines are used, and the extraction yield is (1-0.41 ³ ) × 100 = 93% if ^three osmators are used.

After extraction, methanol is substantially removed from the osmosis unit in a quantitative manner, and the resulting bottom product is about 1/5 of the osmotic volume. Methanol is removed using a vacuum distillation apparatus equipped with a fractionation column. Concern about hydrolysis of sennosides, so that the temperature does not exceed + 50 ℃.

In addition to sennosides, the concentrate contains all the substances that can be extracted from methanol from raw plants. About 5% of butan-2-ol is mixed with the concentrate to keep the fat in the concentrate as an emulsion and to serve as a preservative to prevent microbial growth and solution rot.

After methanol is distilled off, the concentrate is purified by liquid-liquid extraction with an organic solvent. Solvents used are partially water soluble alcohols or ketones, ie butanol, methyl ethyl ketone or isopropyl ketone, the best being butan-2-ol. Liquid-liquid extraction is carried out in a continuous process in a fractionator with a separation effect of about ten theoretical steps. The pH of the influent concentrate is about 5.4-5.6, at which the salt of the aglucon compound present in the senna drug is hydrolyzed to actually remove the aglucon quantitatively from the raffinate.

Butan-2-ol for extraction should be saturated with water before use. The influent concentrate to be extracted is a very concentrated solution containing about 20-30% dry matter. It contains salts, sugars, amino acids and other compounds derived from the original plant material. The extraction is preferably carried out so that the outflow ratio of butan-2-ol to raffinate is 0.7-0.8: 1.

The liquid-liquid extraction method removes fats, harmful plant pigments, chlorophylls and carotenoids, free fatty acids, steroids, aglucanic anthracene derivatives, neutral glucosides, vegetable waxes and wax alcohols, flavones and other phenols from the solution. do. The raffinate produced by this method is free of harmful impurities, and most sennosides can be acidified to pH 1.2-2.0 by a mineral acid such as hydrochloric acid or sulfuric acid and crystallized directly from the raffinate.

In order to crystallize the sennoside from the raffinate phase, it is placed in a container and passed through a certain amount of acid until the pH is about 1.5-2.0 with stirring. Next, sennoside crystals are added to the crystal nuclei in a solution, stirred, and allowed to form for 1 week.

Crystallization may also be carried out using a crystallization apparatus operated continuously. At this time, the raffinate phase stays in the crystallization apparatus for about one week and is divided into two or more continuous containers and flows into the decanter. The crystallization vessel is continuously stirred slowly and the acid solution is added to the first vessel with stirring for acidification. The vertical lamina flow in the vessel is about 0.3-0.4 mm / min. At this flow rate, sufficient precipitation occurs. The crystallized material is filtered off, washed with water and methanol or acetone and dried. If necessary, the crude product is recrystallized as described herein.

In terms of biological activity, an important fraction of senna pharmaceuticals is the portion containing NSLAS. This part is present in various amounts in pharmaceuticals, extracts, and sennases. In addition, these substances are also produced during drug extraction. The laxative effect of the crude NSLAS fraction is about 60% of the effect of the pure sennoside mixture. However, the toxins in the veins of the crude NSLAS fraction are 20 times that of the pure sennoside mixture.

The chemical properties of the NSLAS fraction, the solubility in various solvents, the partial properties, and the salt formation properties, correspond to the properties of sennosides.

The NSLAS fraction contains sennoside residue present in the mother liquor upon crystallization on the raffinate after purification extraction with an organic solvent. The sennoside content of the crude NSLAS fraction is 5-10%. That is, the NSLAS fraction contains 5-10% of line-8-glucoside and 80-90% of the compound, and its chemical structure and physiological action are not known until now. The crude NSLAS fraction is divided into two parts of about the same amount by filtration with 95% methanol. The part insoluble in 95% methanol was brown powder, which was separated by the image of the compound gel chromatography, and it was found to be a homogeneous compound. It had a retention volume of 1000 to 10,000 molecular weight. The fraction soluble in 95% methanol consists of low molecular weight compounds. This fraction contains about 20% sennosides.

Most of this fraction consists of compounds that are unknown or completely unknown in the field of senna pharmaceuticals.

The crude NSLAS fraction is easily separated by the sennoside by mixing the stock solution with a salt (eg sodium chloride). For this purpose, 2 parts by weight of solid sodium chloride is slowly added to 10 parts of the mother liquor while stirring after filtration of the sennoside and the stirring is continued for 1-2 hours. The semi-solids which condensed on the solid surface are then decanted from the solution by decantation, suspended in water and washed, the suspension is stirred overnight, the precipitate is allowed to settle until the next day and the wash is poured out. The precipitate is separated by suction filtration or centrifugal filtration, washed with water and anhydrous methanol and dried over an air stream at ambient temperature. When senna pods are crude, the yield of crude NSLAS is about 1.5-1.6% of the weight of crude used and can be precipitated from dilute solutions by salting out.

If necessary, the crude senonoside obtained by crystallization can be recrystallized. To this end, crude sennosides are suspended in a mixture of water and acetone (50:50) to form a suspension of about 10%, sodium hydroxide is added to form a sodium salt at a pH of 7.5-9, and senenosides are dissolved. Precipitate again, adjusted to pH 1.5-2 with hydrochloric acid, separate, wash with aqueous acetone and dry.

According to the present invention, the laxative compound contained in senna is divided into two parts, namely sennoside and NSLAS. The latter is again divided into two parts (resin and low molecular weight). The alleviation of all parts is about 90% of the total laxative action of senna. The results of laxative and venous toxicity studies in rats are shown in the table below.

[table]

The process according to the invention thus makes it possible to produce sennosides of almost 100% purity from the preparation. Furthermore, the concentrated NSLAS can be separated from the sennoside stock solution. In addition, according to the process of the present invention, there is no need for preliminary extraction of a medicament necessary for the prior art.

Senosides obtained by the process of the present invention are chemically and pharmacologically fully characterized, and thus can be used in the preparation of the false positive component having the properties of the bark of bark. In contrast, according to the known process, only some of the unrestricted herbaceous bark extract is produced.

The present invention also provides a laxative composition mixed with at least one laxative compound produced by the process of the present invention and a pharmaceutical diluent or carrier in solid or liquid. The following examples are intended to illustrate the present invention.

Example 1

40 kg of senna is placed in an osmosis unit (250 liters in volume, covered with a porous steel sheet) connected in two series. The extraction solvent fed to the primary osmosis machine is 70% methanol.

The bottom plate covered with filtration fabric lies at the bottom of the osmosis machine. An empty cock under this plate allows the solution to pass through the medicament in the second osmator and freely flow the solvent in the first osmator. The flow rate of the solvent is controlled by the transport cock of the first osmator. The run-off of the second osmosis unit is adjusted so that the solvent in the second osmosis unit is high enough to cover the porous steel sheet weighing 0.7 kg / dm 2.

A total of 160 liters of solvent is used to extract 40 kg of senna medicine, 70% methanol corresponding to the above amount is allowed to flow through two osmotic devices, and then an appropriate amount of osmotic liquid is collected and an empty osmotic pipe is post-osmosis. Connect to the vessel and pass 60 liters of 70% methanol through the osmosis unit. The remaining glass solvent is then passed from the first osmosis unit to the top of the second osmator and the post-osmosis is collected up to 120 liters. After emptying the first osmosis machine, fill it again with 40 kg of Senna's medicine and send the osmotic water to the medicine with a pump. 120 liters of the osmotic water is sufficient to cover the medicine in the osmotic medicine. The pipe is then circulated from the effluent to the pump and the heat exchanger, from here to the osmotic cap to circulate the solution until the temperature is 30 ° C. Then stay overnight.

The next day, this osmosis unit is connected to the one already extracted and extraction is carried out by the method described above.

Collect 160 liters of osmotic fluid from 40 kg of each drug and remove methanol from the packed column equipped with vacuum rotary evaporator. When about 30 liters of coagulum is produced, it is extracted with butan-2-ol saturated with 40 liters of water in a "mixed precipitation" apparatus (step 10). About 38-40 liters of aqueous raffinate are obtained and about 30-32 liters of butan-2-ol extract is obtained. The aqueous raffinate is acidified with 93% sulfuric acid over 20 hours with stirring. The amount used is 1.6 volume of the volume of the liquid to be acidified. The pH of the acidified liquid is 1.5-2.0. After further stirring for 6 days, the precipitate is deposited overnight, filtered, washed with water until the washed water is colorless, washed with methanol and dried at ambient temperature. The yield is 760-790 g (dry weight) for 40 kg crude, with a sennoside content of 90-94%. This is about 70% of the sennosides present in the crude.

0.5 kg of crude product is suspended in 5 liters of acetone-water (1: 1 volume) mixture and 48% aqueous sodium hydroxide solution is added until the pH is 8.5-9 with stirring. The insoluble residue is filtered off and 35% hydrochloric acid is added to the filtrate until the pH is 1.5-2. Stirring is continued until crystallization begins and left to crystallize for at least 3 hours. The precipitate is filtered off from the solution, washed with 0.5 liters of water, 0.5 liters of acetone and dried in air at ambient temperature. One fifth of the mother liquor is mixed with wash water and washed acetone, and this solution is used as the crystallization solvent of the following equivalent crude product. The yield is 0.460 kg (dry weight) per 0.5 kg crude product with a sennoside content of 98-99%.

Example 2

The same method as in Example 1 is used except that three series of osmosis units are used and 70% methanol is not warmed. Otherwise, 160 liters of solvent per 40 kg of drug is used as described in Example 1. From the drug 40 kg, 0.890 kg (dry weight) of sennoside crude product is obtained (senoside content is 92%). The crude product can be recrystallized as in Example 1.

Example 3

Extraction, removal of methanol from the extract and liquid-liquid extraction are carried out as in Example 1. After treatment with butan-2-ol, the sennoside mixture is crystallized from raffinate in a continuous operation crystallization apparatus. In crystallization, the two vessels connected and the third vessel to the decanter are connected to the other. Precipitation of the sennoside mixture is carried out in the latter vessel, whereby most of the precipitate is separated from the mother liquor. For this purpose, the raffinate phase obtained after purification with butan-2-ol is passed through the first vessel at a rate of about 2 liters / hour. At the same time 93% sulfuric acid in an amount equal to 1.6% by volume of raffinate is pumped into it. At this time, the liquid in the first vessel is continuously stirred to prevent precipitation. The suspension in the first vessel is then flowed non-limitingly into the second vessel equipped with the stirrer, in which the liquid is transferred to the third vessel in a non-limiting flow where precipitation settles out and the mother liquor flows into the waste solvent vessel indefinitely. The precipitate, which is removed as a dense suspension from the third decanter through the coke at the bottom, is aspirated, washed with water and methanol and dried in an air stream at ambient temperature. The yield is 790 g per 40 kg crude used and the sennoside content is 91%.

Example 4

The mother liquor (obtained crystallized in aqueous raffinate) in Example 1 is treated with sodium chloride. For this purpose 40 liters of mother liquor (corresponding to 40 kg of the crude material used) are slowly stirred and mixed with 8 kg of sodium chloride. A brown semisolid precipitate is obtained. Stirring is continued for 2 hours and the precipitate is immersed in the solution until the next day. The mother liquor is decanted and the precipitate suspended in 40 liters of water, stirred for 20 hours and the precipitate settled. The precipitate is then suction filtered, washed with a sufficient amount of water, dried in an air stream at ambient temperature and passed through a 0.5 mm mesh sieve. The yield is 0.60 kg.

High pressure liquid chromatography (HPLC) analysis showed that the precipitate consisted of 5% senamide 5% line 8-glucoside.

Laxative action of this substance is about 85% of the sennoside cyclization effect. Toxicity by intravenous administration to mice is LD ₅₀ = 430 mg / kg. Thus, there is an unknown compound that has a relaxing effect on this fraction but has greater toxicity than sennosides. The laxative effect of the non-senoside fraction is about 40% of the total laxative effect of the original drug and crude extract.

48 g of the crude NSLAS fraction is filtered 12 times with 500 ml of 95% methanol. For this purpose, the ground powder is stirred with 95% methanol each for at least 2 hours. Methanol washing fractions were combined and evaporated to dryness. The weight of the calculated residual amount is 22 g. Its laxative effect is the same as pure senosides and the toxicity is LD ₅₀ i. v = 4100 mg / kg (mouse). The dry yield of the resin material insoluble in 95% methanol is 20.8 g. Its laxative effect is less than 10% of sennosides and toxicity is LD ₅₀ i. v = 130 mg / kg. Thus, the NSLAS fraction separated from the sennoside mother liquor by salting has a laxative effect on the unknown structure and the nontoxic compound dissolved in 95% methanol also has an unknown chemical structure and contains a very low toxicity component. .

Example 5

The extraction, liquid-drug extraction, and recrystallization processes described below are schematically illustrated in the accompanying drawings 1, 2, 3.

The agent is extracted at ambient temperature in a four stage countercurrent osmosis system. At this time, 40 kg of senna pods are injected daily into one of four cone tiles and compressed into a porous plate.

A sufficient amount of 70% methanol is backflowed through the four osmotic devices to completely cover the senonapod with liquid. After at least 12 hours of cold soaking, the osmotic continues until a total of 160 liters of 70% methanol has passed. From the container filled with fresh solvent, connected in series, the extract from the container is passed through completely, and the extract residues are dried for solvent recovery. This container is capable of holding the next 40 kg batch of medication which is connected to the end of the device. The extraction efficiency per osmotic step is about 60%. After about 120 liters of primary extract are obtained from 40 kg of each senna pod, it is concentrated to about 30 liters under vacuum in a rotary evaporator equipped with a fractionation column. The temperature in the production vessel should not exceed 50 ° C.

To facilitate the next liquid-liquid extraction, methanol must be completely removed. After gas chromatography confirms complete removal of methanol, continue to mix this concentrate with about 2% butan-2-ol. The pH value of this extract is about 5.8.

For continuous liquid-liquid extraction, the concentrate is passed through a concentrate in a 10 stage mixed-separator apparatus (each stage about 5 liters) without prefiltration, flowing countercurrent to butan-2-ol. The ratio of butan-2-ol: extract concentrate is 1.5: 1, but the ratio of butan-2-ol extract: extract raffinate is 0.7-0.8: 1. The average residence time at each stage is about 20 minutes. The extracted raffine is then adjusted to pH2 with 94% sulfuric acid and passed through a 3-step crystallization apparatus. Initiate crystallization to initiate crystallization and crystallize at ambient temperature for 5 days.

The resulting crystalline slurry is removed from the bottom of the third crystallization vessel. The discharged crystalline slurry is suction filtered and the mother liquor is returned to the crystallizer. The crystals are first washed with water and then with methanol and then vacuum dried at 40 ° C. Joe Senoside was calculated to be approximately 90% pure. To recover butan-2-ol, the butan-2-ol extract is completely evaporated leaving a dark brown or black residue. The distillate is reused for liquid-liquid extraction.

The resulting crude sennosides are suspended in an acetone / water mixture (50/50) to form a 10% suspension, and when sodium hydroxide aqueous solution is completely dissolved until the pH is about 7.5, sodium salts begin to form.

The pH of the solution is adjusted back to 2 with hydrochloric acid to precipitate sennosides. The precipitated product is separated, washed briefly with aqueous acetone and dried. This method yields about 2% pure sennosides (A and B) for the senna pods used.

Claims (13)

a) extract Senna Pharmaceuticals by reverse osmosis with aqueous methanol and concentrate below 50 ℃ to completely remove the methanol; b) purifying the extract as continuous liquid-liquid extraction with an organic solvent; c) The purified material (laminate) is transferred to a crystallization apparatus and acidified with stirring (pH 1.5-2.0), the sennoside crystals are introduced into the crystal nuclei, the stirring is continued, crystals are formed, and the resultant sensonoside crystals are separated. The process of making a laxative from senna. The process according to claim 1, wherein 70% methanol is used as the extraction solvent of step a). The process according to claim 1, wherein the extraction of step a) is carried out at an increased temperature up to 35 ° C. The process according to claim 1, wherein the reverse osmosis process is carried out in an osmosis device connected in two to four series. The process according to claim 1, wherein the swelling agent is swollen with a post-osmotic material before osmosis. The process of claim 1 wherein the concentrate obtained in step a) is mixed with about 5% butan-2-ol. The process according to claim 1, wherein the organic solvent used in step b) is butanol, methyl ethyl ketone or methyl isopropyl ketone. The process according to claim 1 or 7, wherein the organic solvent used is butan-2-ol saturated with water. The process according to claim 1 or 7, wherein the effluent ratio of butan-2-ol: raffinate is 0.7 to 0.8: 1. The method of claim 1, wherein the acidification process of step c) is performed by hydrochloric acid or sulfuric acid. The method according to claim 1 or 10, which is suspended in an acetone-water (50/50) mixture to obtain about 10% suspension for recrystallization of the sensonoside obtained in step c) and hydroxylated until the pH is 7.5-9. Dissolving completely by adding sodium, and forming a sodium salt, adjusting the solution with hydrochloric acid so that the pH of the solution is about 1.5-2, reprecipitating and separating senosides, followed by washing with aqueous acetone and drying. a) extract the Senna Pharmaceuticals by reverse osmosis with aqueous methanol and concentrate below 50 ℃ to completely remove the methanol; b) purifying the extract as continuous liquid-liquid extraction with an organic solvent; c) The purified material (laminate) is transferred to a crystallization apparatus and acidified with stirring (pH 1.5-2.0), the sennoside crystals are introduced into the crystal nuclei, the stirring is continued, crystals are formed, and the generated sensonoside crystals are separated. Doing it; d) recrystallization; e) 10 parts by weight of the mother liquor of c) was stirred and mixed with 2 parts by weight of sodium chloride, the surface semisolid coagulum was decanted and washed, extracted with 95% methanol, the methanol fraction was concentrated and the residue was dried. And a process for preparing a laxative agent from Senna Pharmaceuticals. The process of claim 8, wherein the ratio of butan-2-ol: raffinate effluent is from 0.7 to 0.8: 1.

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