Drug – bio-affecting and body treating compositions – Antigen – epitope – or other immunospecific immunoeffector – Conjugate or complex
Reexamination Certificate
2001-02-16
2003-01-14
Barts, Samuel (Department: 1623)
Drug, bio-affecting and body treating compositions
Antigen, epitope, or other immunospecific immunoeffector
Conjugate or complex
C424S725000, C536S018500, C536S123100, C536S127000, C536S128000, C514S054000, C514S862000, C514S863000, C514S886000, C435S029000, C435S032000
Reexamination Certificate
active
06506387
ABSTRACT:
BACKGROUND OF THE INVENTION
The present invention refers to a method for the preparation of aloin, more particularly to a method for extracting aloin from aloe juice, or of derived products that is of industrial utility and gives a final product of good purity in satisfactory yields.
Aloin is a natural substance that can be obtained in a classical way by extraction starting with aloe gel. It is a highly interesting substance owing to the pharmacological properties of several derivatives that are of utility in diverse medications. The rhein for instance, which can be obtained from aloin, has the properties of a laxative, antirheumatic, antiarthrosic, and antiarthritic useful in therapy.
The methods that have most commonly been used over numerous years, generally consist in an extraction starting from hard gum, that is, from a hardened residue obtained when concentrating the juice by simple heating in the open air under atmospheric pressure. The extraction yields aloin that can be purified by recrystallization in an appropriate solvent.
The patent EP-A-374 890 describes a method of extraction of the aloin and aloe emodin from plants or plant extracts with a hydrophilic solvent, filtration, and evaporation to obtain a syrup which is then subjected to several extractions, then a recrystallization. The solvents used are alcohols, acetone, ethyl acetate, and water.
The usual chemical designation of aloin is 10-glucopyranosyl-1,8-dihydroxy-3-hydroxymethyl-9(10H)-anthracenone. Aloin exists in the form of two isomers, A and B, which differ by the position of the glucose group at the anthrone base, their proportions being susceptible to vary depending on the origin of the plants and on the extraction methods used. An aloin with a high content of isomer A is generally preferred.
SUMMARY OF THE INVENTION
Studies and tests performed by applicant have shown that it was possible to significantly improve the classical extraction method by using an additive that facilitates the extraction and subsequently allows the purification to be improved. In particular, the method according to the invention yields an improved selectivity of extraction and considerable decrease in the amounts of solvent used in the purification under the conditions under which the method is practiced on an industrial scale.
The method of preparing aloin according to the present invention essentially comprises an extraction of an exudate of aloe, particularly of the yellow juice of aloe, for instance of aloe barbadensis or also aloe capensis, or a derived product, in the presence of an aliphatic diol or triol of low molecular weight, followed by a purification by crystallization.
According to a preferred embodiment, the aliphatic diol or triol of low molecular weight is added in a first step to the yellow aloe juice, and a concentration is performed, then an extraction is realized in a second step. This first step can of course be realized with an aloin-containing derivative of the juice such as hard gum, but it is preferred to directly use the yellow juice, which corresponds to a less degraded substance.
The extraction is followed by a recrystallization from an alcohol that can be selected among ethanol, n-propanol, isopropanol, n-butanol, tert-butanol, and isobutanol.
According to the present invention, the expression “aliphatic diol or triol of low molecular weight” designates a diol or triol with no more than 15 carbon atoms in its carbon chain, preferably no more than ten carbon atoms. The aliphatic diol or triol of low molecular weight used in the invention can for instance be a glycol or glycerol. The glycol is preferably selected from ethylene glycol, diethylene glycol, propylene glycol, butylene glycol, tripropylene glycol, and triethylene glycol. The aliphatic diol or triol is used in amounts between 5 and 25% by weight, preferably between 7 and 15%, relative to the weight of yellow juice used as the starting material.
As indicated above, after concentrating the yellow juice in the presence of aliphatic diol or triol one performs the extraction with a solvent selected preferably among ethyl acetate and acetone.
For satisfactory yields, the extraction solvent selected is important. Thus, comparative tests have shown that the overall yield relative to the aloin present in the starting material is about 50% when ethyl acetate is used, while the extraction is poor, that is, below 10%, when chloroform or petrol ether are used. The purity of the product after extraction, that is, its aloin content, also is below 10% when the ethyl acetate or acetone are replaced by chloroform.
The method of the invention leads to an important improvement in extraction selectivity over the classical methods, since the aloin content of the extracted product prior to purification is of the order of 60%, while it is around 50% in the case of an extraction by a usual method.
The quality of the aloin obtained, and its overall yield, can be optimized when the water content is controlled during purification by recrystallization from an alcohol. Thus, according to an advantageous feature of the invention, the purification by recrystallation is performed in the presence of 0.5 to 5%, preferably 0.5 to 2%, by weight of water relative to the medium's total weight. The amount of water can be adjusted as usual, either by adding water when its content is low, or by azeotropic distillation when it is high.
The method according to the present invention allows a product to be obtained which has an aloin content of over 80%, generally between 85 and 90%, and even higher than 90%, when the water content during purification is controlled. Under the conditions that are applicable when realizing the method on an industrial scale, the overall yield relative to the aloin present in the starting material (yellow aloe juice or derived product) is higher than 50%.
Another advantage of the method of the invention is that of allowing an important reduction in the amount of alcohol used in the purification step following extraction. Thus, in the case of a recrystallization in isobutanol, the amount of alcohol is between 10 and 20 volumes per volume of aloin present in the medium, as against 40 to 60 volumes in the usual methods.
The aloin obtained by the method of the invention can be used to prepare medications on the basis of rhein or of derivatives that are used in treating arthrosis, arthritis, and various inflammations.
REFERENCES:
patent: 4602004 (1986-07-01), Cohen
patent: 4670263 (1987-06-01), Noorlander
patent: 4957907 (1990-09-01), McAnalley
patent: 4966892 (1990-10-01), McAnalley
patent: 5330756 (1994-07-01), Steuart et al.
patent: 6290964 (2001-09-01), Shupe et al.
patent: 6309675 (2001-10-01), Sobczak
patent: 0 374 890 (1990-06-01), None
patent: WO 87/00052 (1987-01-01), None
Barts Samuel
Browning Clifford W.
Khare Devesh
Paxa N.V.
Woodard, Emhardt, Naughton Moriarty & McNett LLP
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