Classifications

• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
  • A61K36/18—Magnoliophyta (angiosperms)
  • A61K36/185—Magnoliopsida (dicotyledons)
  • A61K36/28—Asteraceae or Compositae (Aster or Sunflower family), e.g. chamomile, feverfew, yarrow or echinacea
• • C—CHEMISTRY; METALLURGY
  • C07—ORGANIC CHEMISTRY
  • C07D—HETEROCYCLIC COMPOUNDS
  • C07D311/00—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings
  • C07D311/02—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings ortho- or peri-condensed with carbocyclic rings or ring systems
  • C07D311/04—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring
  • C07D311/22—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring with oxygen or sulfur atoms directly attached in position 4
  • C07D311/26—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring with oxygen or sulfur atoms directly attached in position 4 with aromatic rings attached in position 2 or 3
  • C07D311/40—Separation, e.g. from natural material; Purification

Definitions

• This invention relates to a novel and improved process for recovering polyhydroxyphenyl chromones. More particularly this invention relates to a method for recovering polyhydroxyphenyl chromones having valuable pharmacological properties.
• the ternary system methanol/water/petroleum ether avoids the disadvantages associated with the methanol/ petroleum ether system.
• the most favorable methanol/ water/petroleum ether mixture has been found to be methanol/water (95:5) as lower phase in equilibrium with pure petroleum ether, wherein the petroleum ether has a boiling point of from 40 to 60 C.
• the system in equilibrium furthermore had the advantage of an unexpected shifting of the distribution values in favor of the desired purification process for the active substances.
• the applicants invention therefore lies in a method for recovering polyhydroxyphenyl chromones which comprises subjecting the dried fruits of Silybum marianum Gaertn. to high mechanical pressure, for example in a screw press, whereby the cell walls are ruptured and freed of the major amount of fatty oils contained therein, exhaustively extracting the remaining solid residue from the press which still contains oil in an amount of 5 to 10% with ethyl acetate, evaporating the ethyl acetate, dissolving the oil-greasy, partially lumpy dry residue thereby obtained and which contains about 20 to 30% of active material to form a concentration thereof of 2 wt.
• a solvent system consisting of, for example, methanol water, and petroleum ether in order to separate therefrom the undesirable by-products, centrifuging the solvent system for removal therefrom of flaky solid material constituting impurities and undesirable by-products, thereafter subg'ecting the solvent system to a multiplication, preferably uniform distribution by countercurrent contact of the upper and lower phases, and recovering from the lower phase by concentration in vacuo a brownish powder containing 70 to of polyhydroxyphenyl chromones.
• the lower phase becomes enriched in active material and may be recovered with the lower phase at the discharge end of the apparatus.
• the purified active materials in the form of a beige-colored dry product by the evaporation of the lower phase.
• the dry product contains 70-80% silymarin and may be used in this form directly or it may first be subjected to further purification and/or separation procedures.
• the material having the largest R -value silymarin I was established as to its basic structure. It has the empirical formula C H O and is a 5,7-dihydroxy-2- (3-methoxy-4'-hydroxyphenyl)-chromanone-3-ol which is substituted in the 7-position with a C H O -radical. It has a melting point of 167 C.
• silymarin for the product of the process of the invention which consists of a mixture of the materials I, II, III and IV and to designate the individual components as silymarin I, silymarin II, silymarin III and silymarin IV.
• Silymarin I can be directly separated from the lower phase running off the distribution apparatus by crystallization.
• the lower phase after treatment with active charcoal is at first only compressed to such an extent that after the removal of the active charcoal on further compressing, silymarin I is separated in crystalline form.
• the recovery of polyhydroxyphenyl chromones, and particularly of silymarin and/or its components as set out above comprises in accordance with the invention the following steps:
• EXAMPLE 1 100 kg. of the dried fruits of Silybum marianum were freed from the main amount of fatty oils contained therein using a screw press as conventionally used for oil seeds under high pressure of from 250 to 280 kg./cm. There were thereby obtained approximately 75 to 80 kg. of press residue having an oil content of 5 to 10%.
• the flow velocity of both phases depends extensively on the degree of efficiency of the emulsifying units and on the separators.
• the optimum regulation can be ascertained gravimetrically by quantitative determinations of the transition values of the active material.
• the lower phase (about 300 l.) discharged from the distribution battery was dried in vacuo at 20 mm. Hg and resulted in a biege-colored to brownish powder in a weight yield of 3.1 kg.
• the content of active material (silymarin) amounted to between 70 and 80%, with a yield of active material of 2.2%, calculated on the starting material.
• the lower phase (about 300 l.) leaving the distribution battery was collected, treated with 1.5 kg. of active charcoal and compressed to 100 l. in vacuum at 20 mm. Hg.
• the solution while still hot was purified on a filter press and afterwards further compressed. In the range of about 50 to 30 1. remaining volume, an increasing crystallization is initiated. Depending on the degree of concentration, a white to ochre-colored crystallizate was obtained.
• the crystallizate had a melting point of 167 to 169 C. It consisted of silymarin I and had a degree of purity of 95 to 100%.
• polyhydroxyphenyl chromones obtained according to the method of the invention demonstrated in experimental tests carried out on animals a marked protective effect against liver-damaging influences of various toxicants.
• the degree of liver damage for instance produced with carbon tetrachloride, can be determined for example by the hexobarbital period of sleep. Inasmuch as damaged liver cells cannot rapidly catabolize the hexobarbital, the period of sleep is very appreciably prolonged in the case of liver damage. When silymarin was administered previous to the hexobarbital, there resulted a shortening of this period of sleep prolongation by 59.2%, i.e., an antagonization of the effect of the carbon tetrachloride by the silymarin.
• a liver damaged by carbon tetrachloride furthermore is able to catabolize p-oxyphenyl pyroracemic acid only to a diminished extent, which for this reason therefore appears in increased amounts in the urine.
• Untreated rats excreted within four hours 10% of the amounts of poxyphenyl pyroracemic acid given, while rats damaged by carbon tetrachloride excreted If, however, they had previously received silymarin, the excretion time normalized at 810%. The animals behaved as if there had not been any liver damage by the carbon tetrachloride.
• silymarin in protecting the cell structure and the cytometabolism was also confirmed in numerous further experiments. Even damage which had already occurred could be reversed by administering silymarin. It was established by electron-microscopic examination that the structure of the mitochondria and of the endoplasmatic reticulum considerably destroyed after administering wamanitine could be fully restored again by silymarin. The restoration of the disturbed integrity means that silymarin does not only have a protective but also a stabilizing effect.
• the immediate eifect on the structural elements of the liver cell provides for a completely novel form of therapy.
• Process for recovering silymarin comprising polyhydroxyphenyl chromanones which comprises (1) subjecting the dried fruits of Silybum marianum Gaertn. to high mechanical pressure, whereby the cell walls of the fruits are ruptured and the major amount of fatty oils contained in the fruits is separated therefrom, (2) exhaustively extracting the remaining solid residue which still contains fatty oils in an amount of about 5 to 10% with ethyl acetate, (3) evaporating the ethyl acetate, (4) dissolving the oilgreasy, partially lumpy dry residue thereby obtained in a solvent mixture comprising methanol, water and petroleum ether whereby an upper phase and a lower phase are formed and wherein said chromanones are contained in the lower phase, (5) centrifuging said solvent mixture to remove any solid material present therein and separating the upper and lower phases, (6) thereafter subjecting the liquid portion comprising the lower phase to multiple countercurrent contact with petroleum ether, whereby a thorough mixing and separation of both phases occurs, and (7) recovering the polyhydroxyphenyl

Landscapes

• Health & Medical Sciences (AREA)
• Natural Medicines & Medicinal Plants (AREA)
• Chemical & Material Sciences (AREA)
• Organic Chemistry (AREA)
• Life Sciences & Earth Sciences (AREA)
• Microbiology (AREA)
• Pharmacology & Pharmacy (AREA)
• Botany (AREA)
• Medical Informatics (AREA)
• Medicinal Chemistry (AREA)
• Alternative & Traditional Medicine (AREA)
• Mycology (AREA)
• Biotechnology (AREA)
• Epidemiology (AREA)
• Animal Behavior & Ethology (AREA)
• General Health & Medical Sciences (AREA)
• Public Health (AREA)
• Veterinary Medicine (AREA)
• Engineering & Computer Science (AREA)
• Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)

Applications Claiming Priority (2)

Publications (1)

Family

ID=25755470

Family Applications (1)

Country Status (9)

Cited By (3)

Families Citing this family (2)

• 1969
  • 1969-05-27 US US00828353A patent/US3773932A/en not_active Expired - Lifetime
  • 1969-05-29 CA CA053,025A patent/CA1029735A/en not_active Expired
  • 1969-05-30 NL NL6908301A patent/NL6908301A/xx unknown
  • 1969-05-30 SE SE6907652*A patent/SE371931B/xx unknown
  • 1969-05-30 GB GB1257956D patent/GB1257956A/en not_active Expired
  • 1969-05-30 LU LU58751D patent/LU58751A1/xx unknown
  • 1969-05-30 BE BE733911D patent/BE733911A/xx not_active IP Right Cessation
  • 1969-06-02 OA OA53625A patent/OA03888A/xx unknown
  • 1969-06-02 FR FR6918088A patent/FR2010026A1/fr active Pending

Also Published As

Similar Documents