Process for obtaining laxative compounds from senna drug

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 translated from Korean
Process for producing a laxative from senna drug
The first is to turn the flowchart of the extraction process of the present invention.
A flow chart of the liquid extraction process - first turning the liquid phase of the present
invention.
3 is a flowchart of a turning recrystallization process of the present invention.
The present invention relates to a process for preparing a laxative from senna drug (Senna
drug).
Senna drug consists of geonyeop and pods of senna, senna is a plant which Indian senna
(not old Stephen polyamic, Cassia anqustifolia Katia) and Egyptian senna (Cassia Akti
polyamic, Cassia acutifolia). Caused by the laxative action of the senna drug is a compound
of the two acids contained, i.e., side stream senno (sennosides) and non senno side laxative
agent (hereinafter referred to as NSLAS).
Laxative agent in the senna drug is line (rhein) and aloe-a bimolecular glycoside derivatives
of the two anthracene compound, emodine (aloe-emodin) in the. The most important senno
a side A, B, A 1, C and D. Senno side A, B, and A 1 is bis-di-emodine the anthrone
compounds in-glucosidase sila of anthrone, and senno side C and D of glycoside sila-
glycosyl aloe.
In addition to the metallocene nosayi Drew, ln original drug, ah it may contain gluconate
(Sen nidin) and side senno derivatives and degradation products as well. Although these
while it is in a laxative effect, but produces a side effect at the same time it has a toxicity.
The typical side effects nausea, vomiting, wind (wind), abdominal pain, diarrhea.
There extracting a substance with a laxative effect from senna drug has been announced
several steps so far. Laxative side castle glucosidase most important acids (senno side A,
Claims (13) translated from Korean
1. a) and then it was extracted the senna drug by reverse osmosis with aqueous
methanol and concentrated at below 50 ℃ completely remove the methanol; b)
the continuous liquid with an organic solvent-purifying the extract as a liquid
extract, and; c) acidification and the purified material (laminate) was stirred
transferred to a crystallizer and (to put pH 1.5 ~ 2.0) senno side determined by
the nucleation, still and separating the crystals are generated and the resulting
Jochen furnace side determines the stirring process for producing a palliative
from senna drug consists in that year.
2. The method of claim 1, wherein, a) the process which comprises a step
using 70% methanol as the extraction solvent.
3. The method of claim 1, wherein, a) the extraction process of stage
process, characterized in that this is carried out at elevated temperature
up to 35 ℃.
4. The method of claim 1, wherein the step of reverse osmosis
characterized in that the process is carried out in the osmotic device that
is connected to 24 different series.
5. The method of claim 1 wherein the process comprising a step of
swelling by water seepage after the senna drug before osmosis.
6. The method of claim 1, wherein, a) a concentrate calculated in the step
process, characterized in that mixed with about 5% butane-2-ol.
7. According to claim 1, b) step, characterized in that the organic solvent is
a butanol, methyl ethyl ketone or methyl isopropyl ketone used in step.
8. According to claim 1 or 7 wherein the step of using the organic solvent
characterized in that the all-butane-2-saturated with water.
B), the top was first isolated from senna drug by Stoll (see:. Helv, Chim, Acta XXXII,
FasciculusVI (1949), 1892). It has also been a number of patent publications published 9. According to claim 1 or 7, wherein the butane-2-ol: Step 1,
about the production process of water enrichment senno side. characterized in that: the raffinate effluent ratio of 0.7 to 0.8.

So far, Senna extraction has been carried out in two stages. On the first step, pigment, fat 10. According to claim 1, c) the acidification step process situation,
and other impurities are chloroform, ether is removed with a suitable solvent, such as (see: characterized in that is carried out by hydrochloric acid or sulfuric acid.
U.S. Patent No. 3089814 No.), or 90% methanol (Federal Republic of Germany Patent
Application No. 16 17 667 the call reference). At the end of this primary extract, as the 11. 3. A method according to claim 1 or 10, wherein, c) acetone for re-
second phase, is extracted with only current active glucoside is methanol, aqueous crystallization of the furnace side Jochen obtained in step-water (50/50)
methanol, aqueous ethanol or water. hydroxide were suspended in a 10% suspension mixture and a pH of 7.5
to 9 until a process, comprising a step after completely dissolved by the
And to facilitate the extraction, once in methanol, the alkali added to the organic base used
addition of sodium, and having a sodium salt, pH is adjusted with
Chemistry (see Federal Republic of Germany Patent Application No. 23 397). Organic
hydrochloric acid to about 1.5 to 2 in the solution washed with aqueous
bases are created for the sea salt in methanol, which can be easily extracted with a
acetone, after which re-precipitation separation handed down the senno
metallocene nosayi Drew. However, disadvantages of this process is the high impurity
side and dried.
content in the extract.
12. a) and then it was extracted the senna drug by reverse osmosis with aqueous
Other citric acid has been proposed to use the extract was acidified with: (United Kingdom
methanol and concentrated at below 50 ℃ completely remove the methanol; b)
Patent Application No. 832, 017 cross-references), a solvent (see French Patent Publication
the continuous liquid with an organic solvent-purifying the extract as a liquid
No. M 6611 (1969)), or fish. In the latter case, the solvent is 70% ethanol was used. When
extract, and; c) acidification and the purified material (laminate) was stirred
extracted using a methanol aqueous solution of acidic methanol or acidic, it is reduced than
transferred to a crystallizer and (to put pH 1.5 ~ 2.0) senno side determined by
when the impurity content in the extract have been extracted by using only the basic solvent
the nucleation, still and separating the crystals are generated and the resulting
or water. However, even this process, there is a disadvantage that sometimes exists as a free
Jochen furnace side determines the stirring done that; d) recrystallization, and;
acid, almost insoluble in the acidic compound of the side senno the solvent used. Thus, the
e) c) the mother liquor and 10 parts by weight by mixing sodium chloride, 2
greater the amount of solvent required for the extraction and may result in as much as 15 to
parts by weight with agitation and washed after decanting the semi-solid
20 times the weight of the raw material keojilsu medicament. Furthermore, in the extraction
coagulum on the surface, and then extracted with 95% methanol, and
of the drug, phosphoric acid (see: Hung Teljes 6006 (1973)..) And the aqueous solution of
concentrate the methanol fraction and drying the residue of the process for
phosphoric acid: Acidified with (see JP Federal Republic of Germany Patent 16 17 667
producing a laxative configured from, senna drug.
No.) in methanol-tetrahydrofuran, methanol-dioxane tetrahydrofuran - is known to use a
mixture of dioxane as a solvent. However, the solvent should have a pH value 13. The method of claim 8, wherein the butane-2-ol: raffinate effluent ratio
corresponding to activate the glucosidase enzyme, hydrolyzing a glucoside active part (in of 0.7 to 0.8: Process according to claim 1.
particular when used in a weakly acidic solution) Ingredients. This reduces the amount of
active substance in the extract (see Federal Republic of Germany Patent Application No. 29
15 063).

According to the line technology, senno side concentrate is calculated by a variety of

methods.

Solid, senno side-containing extract is calculated by gradually drying the extract (see
Federal Republic of Germany Patent Application No. 16 17 667). The thus obtained
product There is contained all the material in the extract senno side content is about 17-
18%.

However senno side may make it more selective separation when precipitated from aqueous
solution by addition of an organic solvent. Ln the thus obtained material may be found to a
lesser extent is stable material, the side senno content is 60-70%. Needle phone diethyl
ether (see French Patent Publication No. M611: Magyar G., etc., Hung Teljes, 6006 (1973)
and then added to isopropyl alcohol, a strong acid ion rehabilitated resin (see British Patent
Publication No. 832 017) or ethanol ( see also: Finland is carried out by the patent
publication 41 588) processing solution in the senno side is converted into the calcium salt
(see: U.S. Patent No. 3089814 Finnish Patent Publication No. 41 588) continues to call
needle by the addition of an organic solvent activated glucoside calcium salt as is
calculated. senno a side content in the precipitate is 60 to 70%.

In order to obtain pure senno side as the free acid, thereby decomposing the senno side it
called the calcium salt form with hydroxyl (see:..., Etc. Stoll, Helv Chim Acta XXXII,
Fasciculus VI (1949), 1892).

According to the process known from the above, a variety of concentrate and extract
containing the substance with a laxative action can be seen that can be prepared in senna
drug. The amount of the laxative action substance in the concentrate depends on the
production process used and the amount of the substance in the original medicament. One
kinds of difficult to standardize it senna manufacturing process is to measure the senna
glycosides. Ln medicament, there are contained various compounds contained in the
measurement of senna glycosides acids. However, the physiological function of each of
these materials are not the same. By a commercially available measuring method is, to each
other, because it is impossible that distinguish senna glycosides other physiologically
functional and from possibly have side effects compounds, such as not the senna extract
produced by a conventional method as starting materials it is difficult to produce a
substance that acts of reproduction is always the same capacity.

One of the objects of the present invention is in developing a process for obtaining a
laxative from senna drug to provide a laxative agents, to provide a process that allows
improving the yield and remove the component that causes unwanted side-effects as the
most concentrated form capable will be.

Obtain a laxative from senna drug in the present invention is composed of the following
Tange of:

a) is concentrated at a temperature below 50 ℃ reflux the senna drug by osmosis, until after
the methanol is completely removed, extracted with aqueous methanol;

b) a continuous liquid phase of the extract with an organic solvent-extraction and

purification by liquid;

c) to be given and the purified material (Raffine Id raffinate) was stirred transferred to a
crystallizer pH is acidified until at about 1.5 to 2.0 and put senno side crystal seeding
(seeding) and stirring was continued, and continues the crystallization operation, and , the
resulting crystalline crude (粗) senno then remove the side;

d) if necessary, re-crystallization and the crude senno side;

e) (c) 2 parts by weight of the sodium chloride stock solution and 10 parts by weight of the
step (2 fractions) and stirred with a weight mixture by removing the semi-solid coagulum
on the surface by decanting and washing was then extracted with 95% methanol and
concentrated it next, it dried.

To practice the process of the present invention, methanol and water mixture is used when
the senno side is soluble. The maximum solubility of senno side of the methanol is
preferred to use a 70% methanol because methanol concentration between 60 to 70%.
When the extracted part by a bit in the warm state, but the maximum temperature is + 35
℃. It may cause the senno side of decomposing should avoid a high temperature. However,
surprisingly, it discovered the case of using methanol as solvent the temperature is slightly
increased also does senno side is not degraded.
Reflux halttaeneun the medicament extraction uses an osmosis. Generally it is used groups
2-4 osmosis. Heating the extraction solvent should be purified through a halttaeneun the
external heat exchanger by heating to temperatures up to 35 ℃. The multiple write an
osmotic solvent it should be less warm. The obtained extract contains less harmful
impurities and senno side is completely crystallized from the mother liquor.

The former, the drying agent referred to in extracting good solvent because, after the
extraction from the drug before - is because preferable to use osmotic water. For this
purpose, it is covered with a porous plate into the drying groups osmotic agent with a
weight of about 0.7 ㎏ / d ㎡ solvent and then - makes it possible to pass through the
osmosis water. By weight of solvent required is about 3 times the dry weight of drug.
Drying agents it is preferable to dueotdaga next extraction overnight in solvent.

The extraction time is at least 16-20 hours, haedunda of 70% methanol of a quantity not
required movement to flow through the dry product. It is preferred to use 5-6 group
osmosis, it has passed through the inside of the first solvent to a continuous three
speculative extraction. The speculation is that within three and a few extracts from the
juneunde put the weakest drug where it then becomes empty. The thus having passed
through the osmosis solvent will be passed through osmosis and then this stage. The
primary extract is received in the last three speculative. After an appropriate amount of the
extract is removed, In addition, the seepage water is obtained after which may be used to be
called a new batch (batch) of the dry medicament. GB osmosis that contains the content of
the low drug empty for any purpose that is being filled with drugs osmosis water passes and
performs the next extraction.

According to the process of the present invention can be added one drying agent to extract
only the solvent extraction unit 4. If using 70% methanol at ambient temperature is from
about 41% per sam the residual amount in the drug dumping. If using a two-osmotic
extraction and yield (1-0.41 2) × 100 = 83 %, if using a three-osmotic extraction yield is the (1-
0.41 3) × 100 = 93 %.

After the extraction is completed is removed from the speculative three substantially
determined by methanol is a three speculation is about 1/5 volume of the sediment (botton
product) calculated. Methanol is removed using a vacuum distillation apparatus a sensible
column system. The concerns the hydrolysis of the senno side to the ambient temperature
so that it is not more than + 50 ℃.

Ln addition to the concentrate side senno contains all the substances which can be extracted
from the raw material for methanol plants. Keep the concentrate in the fat emulsion and a
preservative role to be mixed with butane-2-ol of about 5% and concentrate the corruption
of the microbial growth with a solution to be prevented.

And purified by liquid extraction - the liquid phase was removed by distillation of
methanol, the concentrate with an organic solvent. The solvent is used there is a part that is
butanol, methyl ethyl ketone or diisopropyl ketone in a water-soluble alcohol, ketone or the
best thing is a butane-2-ol. Liquid-liquid extraction is carried out in a fractionation device
having a separation efficiency corresponding to about 10 theoretical steps in a continuous
process. The pH of the concentrated solution is introduced is about 5.4 to 5.6 Ah salt of
gluconic compound present in the senna drug at the pH is hydrolyzed aglucone are actually
quantitatively removed from the raffinate.
Butane-2-ol used for extraction is preferably to saturate with water before use. Inlet
concentration to be extracted water is a highly concentrated solution containing a dry
product of about 20-30%. And it still can contain the salts, sugars, amino acids and other
compounds derived from the original plant material. Extraction is a butane-2-ol for ( 對 )
outflow rate of the raffinate from 0.7 to 0.8: 1 such that it is preferable to perform.

Liquid - by liquid extraction, fats, harmful plant pigments, chlorophyll and carotenoid
acids, free fatty acids, steroids, Oh glue conic anthracene derivatives, neutral glucoside
acids, vegetable waxes and wax alcohols, flavones and other phenols, etc. are removed
from the solution do. The raffinate contains no harmful impurities calculated by this
method, most senno side is a pH of 1.2 to 2.0 by acidification in the mine, such as
hydrochloric acid or sulfuric acid can be directly crystallized from the raffinate.

While from the raffinate stirring to this vessel in order to crystallize the senno side causes a
certain amount of acid pH is passed through until about 1.5-2.0. Next, to put senno side
determined by nucleation in the solution for stirring and placed so that a decision for a
week.

It may also be done by using the crystallization apparatus is continuously operating

crystallization. At this time, the raffinate phase is stayed about a week jongan in
crystallizer, so divided in at least two consecutive container flows into a decanter.
Crystallization vessel is gradually stirred continuously and the mine The first solution with
stirring to the acidified placed in a vessel. Vertical laminar flow in the vessel is from about
0.3-0.4㎜ / min. That sufficient precipitation phenomena occur in this flow. Was filtered
bunrae a crystallized substance is dried by washing with water and methanol or acetone. If
necessary, thereby recrystallizing the crude product as explained here.

Important senna drug fraction in terms of biological activity is the part that contains the
NSLAS. This part is present that the amount is varied in the under Article, extract, senna
claim. In addition, such substances are produced during the extraction agent. Division
laxative effects of the NSLAS fraction amounts to approximately 60% of the effect of a
pure side senno mixture. However, for the vein of the crude toxin NSLAS fraction is 20
times of pure senno side mixture.

Properties of NSLAS fraction and solubility, and part characteristics, and characteristics at
the time of salt formation for a variety of solvent corresponds to the characteristics of senno
side.

NSLAS fraction, there is contained a senno side residues present in the mother liquor of the
crystallization time on the raffinate after extraction purification with an organic solvent. Joe
is senno side NSLAS fraction content of 5-10%. That is, the NSLAS fraction is contained a
line-8-glucoside and of 80% to 90% compound of 5 to 10%, and was not known for its
chemical structure and biological action so far. NSLAS crude fraction is divided into two
parts of nearly equal amounts by filtration by a 95% methanol. Insoluble portion of 95%
methanol had a retention volume which inde brown powder do separated by gel
chromatography, compounds of the image know that a homogeneous compound and that
the molecular weight is from 1,000 to 10,000. Fraction soluble in 95% methanol is
composed of compounds of low molecular weight. The fractions are contained senno side
of about 20%.

Most of the fraction is not disclosed either in the field of senna drug consists entirely
unknown compound.

NSLAS crude fraction, a salt (e.g. sodium chloride) to senno sayideuyi stock solution is
easily separated from a mixture with. Stirring by gradually adding solid sodium chloride to
10 parts of 2 parts by weight of the mother liquor was filtered to remove the senno side for
this purpose, and stirring was continued for 1-2 hours. It then the solid surface is semi-solid
materials condensed on the decanted from the solution by decantation, three kind and
stirring the suspension overnight, were suspended in water, and produce along the seated go
precipitate wash liquid until the next day. Remove the precipitate by suction filter or
centrifugal filtration, washed with water and dry methanol and dried in a stream of ambient
temperature. When the pod Senna in crude yield of crude NSLAS is about 1.5-1.6% of the
weight of the crude material used and can be carried out by salting-out precipitation from a
dilute solution.

If necessary, recrystallization of a crude sikilsu senno side calculated by crystallization. For

this purpose the crude senno side water and acetone and suspended in a mixture of (50 50)
and 10 to be the% suspension was dissolved into sodium hydroxide to form a sodium salt to
a pH of 7.5 to 9, a side senno It is isolated by precipitation in a state which is adjusted to
pH 1.5-2 with hydrochloric acid again, dried, washed with aqueous acetone.

According to the invention, the compound contained in senna drug laxative action is
divided into two parts namely senno side and NSLAS. The latter is again divided into two
(portion with a low molecular weight resin). Relaxation of all parts of force is about 90% of
the laxative effect of senna drug. The results of the experiment laxative force and venous
toxicity to rats is shown in the table below.

[table]

Therefore, the process according to the invention can make it produce a senno side of
substantially 100% purity from zero Treaty. Furthermore, it can be separated from the
concentrated juice of NSLAS senno side. Further, according to the process of the invention
eliminates the need for preliminary extraction means of medicaments required for the prior
art.

Senno side obtained by the process of the present invention can be used in the preparation
of uiyang component in the nature of regular chogeun bark so chemically fully tempered
identify pharmacologically. In contrast, according to the known process it is according
become more or less the ratio of the finite chogeun bark extract calculated.

In addition, the present invention provides even and the at least one laxative produced by
the process of the invention compounds, or solid pharmaceutical diluent or carrier and a
mixed liquid of laxative composition. Next, the embodiment of the is to the description of
the invention.

Example 1

Place the senna drug 40 ㎏ in two of the three are connected to a series of speculative
(250 liters volume is covered with a porous steel plate). Extracting the solvent to be
supplied to the primary osmosis is 70% methanol.

The bottom plate covered with filter fabric lies in the three dumping ground. Through the
drug that is in solution, the three speculative second time by the plate carrying the cock
(emptying cock) on the bottom, and flows freely and the solvent in the first osmotic flight.
Flow rate of the solvent it is adjusted by handling the cock of the first three spec. The
effluent (run-off) of the second three speculation is adjusted so that the height of fall of the
second osmotic solvent-flight weight sufficient to 0.7㎏ / d㎡ porous steel sheet to cover.

The solvent of the total of 160 liters is used to extract the senna drug 40 ㎏ , 70%
corresponding to the amount of methanol collected after an appropriate amount of a liquid
osmotic flow through a two osmosis and after the blank pipe of the three osmotic
speculative connects to the container was passed through a 70% methanol 60 liters groups
osmosis. It then glass remaining solvent is collected in the first three to speculation The
second three-pass to the upper portion of the air permeability and, the osmosis water 120 l
after. First, an osmotic then re send senna after 120 liters of water by osmotic drug osmosis
water by a pump and then filled with medicament 40㎏ clearing is an amount sufficient to
cover the drug in three spec. Thereby continuously connected from the effluent by a pipe to
the pump and heat exchanger, up to three speculative lid from here to circulate the solution
until the temperature is 30 ℃. Then allow to stand overnight and then.

The next day, a group connected to the seepage already extracted and the extraction is
carried out by the method described above.

Collecting 160 liters osmotic solution at each drug 40 ㎏ and remove methanol from the
packed column with a vacuum rotary evaporator mounted. After approximately 30ℓ
coagulum is created which extracts "mixed precipitation" saturated butane 40ℓ of water in
the device (Step 10) 2-OLLO. The aqueous raffinate of about 38-40 liters is obtained is
obtained butane-2-ol extract of about 30-32 liters. Sikineunde acidified with stirring over a
period of 20 hours an aqueous raffinate with 93% sulfuric acid usage is 1.6 volume of the
volume of liquid to be acidified. The pH of the acidified liquid is 1.5-2.0. Washed with
water until 6 days immersion was filtered overnight, the precipitate was then stirred for a
further one and three water becomes colorless and then dried in a stream of ambient
temperature, then washed with methanol. The yield is a side senno 760-790g content (dry
weight) for the crude material 40 ㎏ is 90-94%. This is about 70% senno sayideuyi present
in the crude material.

The crude product 0.5㎏ of acetone-water (1: 1 by volume) suspended in a 5 liter mixture
of 48% aqueous sodium hydroxide solution until the pH is 8.5 to 9 is added with stirring.
Filtered off to remove the insoluble residue is added 35% hydrochloric acid to the filtrate
until a pH of 1.5-2 when. It puts to release crystallisation for at least three hours after the
stirring was continued until the crystallization started. And filtered the precipitate from the
solution, washed with water, 0.5 liters, 0.5 liters of acetone and dried in air stream at
ambient temperature. Use this solution to 1/5 of the mother liquor is then mixed with the
wash water and washing with acetone and crystallisation of the crude product of the
solvent, and then an equivalent amount of. Senno side content to yield a 0.460 ㎏
(dry weight) per 0.5㎏ crude product is 98-99%.

Example 2

Using an osmotic connected in series and three with the exception that no allowed to warm
to 70% of methanol is used the same way as in Example 1. If not, the use of solvents of 160
liters per drug 40 ㎏ As described in Example 1. The crude product from the side senno
medicament 40 ㎏ obtained 0.890 ㎏ (dry weight) (senno side content of 92%). The crude
product may be recrystallized as in the first embodiment.

Example 3
Extraction, removing the methanol from the extract, a liquid-liquid extraction is carried out
as in Example 1. In the butane-2-OLLO treated after continuously operating crystallization
apparatus senno side mixture is crystallized from a raffinate. In the crystallization, one third
of the vessel into two vessel and a decanter connected is connected to the other. Senno
precipitation of the mixture is carried out at the side of the container whereby the latter
most of the precipitate is separated from the mother liquor. The resultant product was
purified butane-2-OLLO To this end, the resulting raffinate phase in the first vessel is
passed at a rate of about 2 liters / hour. At the same time, the pump with a 93% sulfuric acid
in an amount corresponding to 1.6% by volume of the raffinate in this. At this time allows
continued stirring the liquid in the first container to avoid precipitation. He then into the
suspension in the first vessel and the stirrer are not limited to leak into the secondary
containment unit is a liquid sedimentation sinking in place after the container has been
moved to the third, but not limited to flow of the mother liquor and exits, but not limited to
waste solvent container. Sucking the precipitate is removed by a dense suspension through
the coke in the bottom from the third decanter was filtered, washed with water and
methanol and dried in a stream of ambient temperature. The yield is 790g per the crude

material using a 40㎏ senno side content was 91%.

Example 4

The exemplary mother liquid (obtained by crystallization from the aqueous raffinate) in
Example 1 is treated with sodium chloride. For this purpose slowly stirring the stock
solution 40 l (corresponding to 40 ㎏ of the original crude material used), and then mixed
with sodium chloride 8 ㎏ . The semi-solid precipitated brown is obtained. Stirring
continued for 2 h and soak in the solution to precipitate the next day. Decanting the mother
liquor and the precipitate was suspended in 40 liters of water and stirred for 20 hours, and
still a precipitate. The thus after suction filtering the precipitate, washed with plenty of
water and passed through the dried material a sieve of mesh 0.5 ㎜ was dried in a stream of
ambient temperature. The yield is 0.60㎏.

Haebomyeon a high pressure liquid chromatography (HPLC) analysis can be seen that the
precipitate is composed of a line sensor 5% 8-glucoside of Norma Id 5%.

Laxative action force of the material is about 85% of the senno side effect cyclization.
Toxicity by intravenous administration to mice is a LD 50 = 430mg / ㎏ . Therefore, this
fraction include, but the relaxation effect, there are compounds of the image has a greater
toxicity than senno side. The non-senno about 40% of the laxative effect of the laxative side
fraction and crude extract The effect of the original medicament.

The crude filtered through 48g of 12 times NSLAS fraction with 95% methanol 500ml. For
this purpose, and the mixture was stirred for at least 2 hours with the pulverized powder
and 95% methanol respectively. And evaporated to dryness The combined methanol wash
fraction. By weight of the calculated residual amount is 22g. Its laxative effect is the same
as pure senno side toxicity LD 50 i. v = 4100mg a / ㎏ (mouse). Yield dry insoluble
resinous substance in 95% methanol is 20.8g. Its laxative effect is not more than 10% of
senno side and toxicity LD 50 i. a v = 130mg / ㎏ . Thus, NSLAS fraction of the by salting
out separation from the mother liquor of senno side is the laxative effect of the structure of
the image and contains a compound also oily fraction has a chemical composition of
unknown toxicity can be very small in a non-toxic soluble in 95% methanol .
Example 5

Extraction, described below, a liquid-weak extraction and re-crystallization process is

shown schematically in the figures 1, 2 and 3 attached.

Drugs are extracted with ambient temperature, in step 4, reverse osmosis device. The daily
injection of 40 ㎏ senna pods of the four groups, one for the cone and is pressed by a
porous plate.

A sufficient quantity of 70% methanol of the senna pods enough to completely cover the
liquid causes a reverse flow through the device, a group of four osmosis. Cold chimhu of at
least 12 hours, and continues the osmosis until a 70% methanol for a total of 160 liters to be
passed. The extract was then passed through a container connected in series from a
container filled with a new and totally solvent, the extraction residue is dried for solvent
recovery. The container is it is connected to the end of the device to accommodate a
medicament for the next batch of 40㎏. Extraction efficiency per osmosis step is about
60%. Senna pods thereby each concentration is about 120 liters from the primary extract
obtained in the 40 ㎏ When the fractionation column, this device rotary evaporator to
approximately 30 liters in vacuo. The temperature in the generating vessel is not more than
50 ℃.

The following liquid-liquid extraction to facilitate this, it should be methanol is removed

completely. And continue the methanol by gas chromatography to confirm the completely
removed to mix the concentrate with about 2% butane-2-ol. The pH value of the extract is
about 5.8.

For the liquid extraction, the mixing step 10, without pre-filtration-continuous liquid
separator unit (each step is about 5 l) to flow countercurrently to the butane-2-ol to pass
through the concentrated water. Butane-2-ol: In case of 1, butane-2-ol extract: The water
extract was concentrated inflow rate of 1.5 the ratio of the extraction raffinate 0.7 to 0.8: 1.
The average residence time in each Bizarro is about 20 minutes. Then extraction Raffine
which in turn is adjusted to pH2 with 94% sulfuric acid and passed through a 3-stage
crystallization apparatus. To put the crystal nuclei for the crystallization starting to
crystallize 5 days at ambient temperature.

And removing the crystalline slurry was calculated from the bottom of the third
crystallization vessel. Suction filtered and the mother liquor is discharged crystalline slurry
was returned to the crystallizer. Washing the crystals with water first, and then washed with
methanol and then vacuum dried at 40 ℃. Division senno side was calculated to be about
90% pure. In order to recover the butane-2-ol, leaving a residue of dark brown or black
when complete evaporation of the butane-2-ol extract. Distillate liquid-liquid extraction is
used again in.

By suspending the crude senno side calculated in acetone / water mixture (50/50) to create
a suspension of 10%, when the pH was completely dissolved into the aqueous solution of
sodium hydroxide until at about 7.5, it begins to be the sodium salt form.

To adjust the pH of the solution with hydrochloric acid again to 2 to precipitate the senno
side. Separating the precipitated product by simply washing with aqueous acetone and
dried. In this way a pure senno side (A and B) of about 2% (with respect to the senna pods
used) is produced.