FIELD OF THE INVENTION
The present invention pertains to the field of Chemistry. More specifically it pertains to a process for the extraction of a pharmaceutically important compound, lysergol from the seeds of an annual herb i.e. Ipomoea herderacea.
BACKGROUND OF THE INVENTION
Lysergol, is an alkaloid of the ergoline family that occurs as a minor constituent in some species of fungi (most within Claviceps), and in the morning glory family of plants (Convolvulaceae), including the hallucinogenic seeds of Rivea corymbosa (ololiuhqui), Argyreia nervosa (Hawaiian baby woodrose) and Ipomoea violacea.
Lysergol belongs to category of API i.e. active pharmaceutical intermediates. It is an off-white crystalline powder with a molecular formula of C16H18N2O and a molecular weight of 254.36. It is having IUPAC name of (7-Methyl-4,6,6a,7,8,9-hexahydro-indolo[4,3-fg]quinolin-9-yl)-methanol (Fig. 1).
(Formula Removed)
Fig.l Structure of lysergol
Pharmaceutical/Medicinal uses of Lysergol
Lysergol has been found to possess interesting physiological properties and a broad spectrum of pharmacological effects. The substance, in very low dosages, acts as a hypotensive agent which is particularly active as to its effect on the peripheral circulatory system. Lysergol exhibits pronounced analgesic and considerable psychotropic properties with antiserotonin effects. It is also used as uterus and intestine stimulating drug.
Lysergol on account of these features can find a useful application in the therapeutics for different pathological situations. To this end it could be formulated in an appropriate manner, as such, or in the form of soluble salts with appropriate excipients suitable for both parenteral and oral use. It has been found that lysergol enhanced the killing activities of different antibiotics on bacteria inspite of the fact that it itself possesses no antibacterial property. So lysergol is used in synergistic antibiotic pharmaceutical composition as bioactive enhancer and bioavailability facilitator for broad-spectrum antibiotics.
Also, the compound is available commercially (Sigma Chemicals, USA). Lysergol is not a controlled substance in the USA. Its possession and sale is also legal under the U.S. Federal Analog Act because of it does not have a known pharmacological action or a precursor relationship to LSD (Lysergic acid diethylamide) which is a controlled substance. However, lysergol can be utilized as an intermediate in the manufacture of some ergoloid medicines like nicergoline which is an ergoloid mesylate, used to treat dementia and other disorders with blood vessel origins. It has been found to increase mental agility and enhance clarity and perception.
Methods of Lysergol Extraction in prior art and their limitations
The compound lysergol is isolated from genera of lower fungi like Claviceps, Penicillium and Rhizopus and from higher plants like Rivea corymbosa, Ipomoea violacea and Ipomoea muricata. Seeds of Ipomoea muricata are commonly known as 'Kaladana' in trade and are being used as a purgative in Pakistan and India. The seeds are a good source of clavine alkaloids. The seeds are reported to contain 0.49% of total alkaloid, out of which lysergol constitutes 53% and chanoclavine 37%. Some patents are available in the prior art which describe the process of extracting lysergol from from genera of lower fungi like Claviceps and seeds of Ipomoea genus. However, the processes of extraction as described in the prior art are entirely different from that of the present invention; have limitations of complexity and yield of impure fractions.
Patent Numbers GB1398997, US3920663 and US4198344 disclose the method for extraction of lysergol from Kaladana seeds. Here, 40 kg of Kaladana seeds are ground and extracted five times with 150 liters of gasoline having a boiling point of 80°C-90°C. The fat-stripped Kaladana upon complete removal of the gasoline is extracted in the same apparatus twice with 160 liters of mixture of chloroform - methanol ammonia in the ratios of 9:0.9:0.1. Subsequently, the mass is extracted thrice with chloroform only (100 litres). The combined extracts are evaporated and the concentrate is allowed to stand in a refrigerator at 0°C - 4°C for two days. The dried cake (300 to 400 grams) is slurried cold in 10 times its weight of water and stirred for one hour. Filtration is repeated and the water insoluble residue is dissolved in thrice its weight of methanol. The organic phase is then further evaporated in vacuo and the concentrate is extracted four times with a 5% solution of phosphoric acid. The combined acidic extracts are made slightly alkaline with aqueous ammonia to a pH of 8 and are extracted with chloroform - methanol mixture in the ratio 7:3. The organic extracts are washed once with water, then dried over anhydrous sodium sulphate and evaporated to dryness under sub-atmospheric pressures at a temperature below 30°C. The purification of the insoluble fraction (Lysergol) is carried out by dissolving the crude product in an equal weight of dimethylsulphoxide, by heating gently on a water bath. The crystallizate is separated by filtration and dried in vacuo to constant weight.
From the above, it is clear that the prior art patents suffer from the limitation of lengthy process of extraction as they require standing time in cold temperature for two days. Also, they do not specify the isolated yield and purity of the product which will reduce the production quantity and affect the commercial viability. However, in present invention, inventor has developed an easy and less time taking procedure and invented a new acid base treatment procedure for obtaining high purity lysergol.
Patent Numbers US181425, EP1370263 and US060604 disclose the process of extracting lysergol from seeds of Ipomoea muricata. The seeds are powdered and defatted with hexane and then extracted with methyl alcohol. The alcoholic extract is dried and extracted with 5-10% HC1 solution. The acidic extract is made alkaline to a pH
of 9.0 and then extracted with chloroform and butanol successively. The crude alkaloid obtained in chloroform and butanol extract is further purified by column chromatography to yield lysergol in maximum yield upto 0.2%.
But the above prior art patents suffer from the limitation that they are not disclosing anything about the purity of product. Lysergol obtained in the present method of invention has higher purity (97%) as detected by HPLC and much higher yield i.e. approximately 3 times (0.65-0.67%) as compared to prior art patents.
A brief comparison of process of extracting lysergol in prior art and that of present
invention is given below in Table 1 and 2.
Comparison between prior art patents and present invention
TABLE 1:

(Table Removed)
TABLE 2:

(Table Removed)
Great emphasis now is being laid towards quality assurance of crude drugs from plants sources widely used in the Indian system of medicine. The scientific study of traditional medicines, derivation of drags through bioprospection and systematic conservation, domestication and cultivation of the concerned medicinal plants has assumed great importance in the present day context when more and more people prefer safe and effective medicines at affordable price for curing their ailments. The present invention enlarges the scope and use of the natural plant compound lysergol that can be used for therapeutical applications because of high purity of product.
OBJECTS OF THE INVENTION
The invention has the following objects:
1. To disclose a novel process for extracting lysergol from Ipomoea herderacea which is more efficient in obtaining high percentage of pure lysergol, cost effective and easier than the processes existing in prior art.
2. To disclose a novel process for extracting lysergol from Ipomoea herderacea which overcomes the drawbacks of previously reported methods mainly the lengthy process of extraction.
3. To disclose a novel process for extracting lysergol from Ipomoea herderacea in which maximum purity is obtained by novel acid base treatment of the extracted lysergol.
SUMMARY OF THE INVENTION
The present invention relates to a novel process for extracting lysergol from Ipomoea herderacea which is easy, less time taking and efficient in obtaining lysergol of high yield and purity. The process of present invention allows commercial scale production of lysergol.
BRIEF DESCRIPTION OF THE DRAWINGS
NIL - No drawings attached.
DETAILED DESCRIPTION OF THE INVENTION
The present invention relates to a novel process for extracting lysergol from Ipomoea herderacea which can obviate the drawbacks of existing process viz. cumbersome extraction and impurity of product obtained
NOVELTY ASPECT OF INVENTION
The present invention discloses a novel process for extraction of lysergol from Ipomoea herderacea which is simple, fast and lysergol obtained is of'97% purity.
INVENTIVE STEP
The inventive step of the process lies in simplification of the extraction process which is eliminating the need for large quantities of defatting agent and the requirement of standing time in cold temperature. Additionally, the process discloses introduction of an innovative acid base treatment and removal of intermolecular water under defined conditions at the second stage of purification resulting in lysergol of very high purity (97%), neither disclosed nor possible in prior art methods.
INDUSTRIAL APPLICATION
The present .method is simple, fast, cost effective and efficient in obtaining high yield and purity of lysergol. The chemicals and reagents required for the extraction of lysergol are easily available commercially. In view of the easy availability of all the chemicals and reagents and simplicity of the process, the present invention allows commercial scale
production of lysergol. The present invention enlarges the scope and use of the natural plant compound lysergol in therapeutic applications because of high purity of product.
NOVEL PROCESS FOR EXTRACTING HIGH PURITY LYSERGOL
The process for extracting high purity lysergol from Ipomoea herderacea involves different steps viz. extraction for lysergol isolation, deffating- cum- first acid base treatment and removal of intermolecular water-cum- second acid base treatment which are described as below: 1. Extraction for Lysergol isolation
1200 kg seeds of Ipomoea herderacea & 120 kg of sodium bicarbonate (SBC) are added to a rotary extractor and 3600 litres (3 times of herb) of dichloromethane & methanol (85: 15, i. e. 85 % dichloromethane & 15 % methanol) are charged in rotary extractor. The pH of solution is adjusted to 8.0-8.5 with ammonia gas at room temperature. The contents are stirred at room temperature for 4 hrs. The solvent mixture is transferred into another vessel for distillation. The second extraction is carried out with 3000 litres (2.5 times of the herb) and pH is adjusted to 8-8.5 with ammonia gas. The stirring is continued for 3 hrs; the solvent is transferred to storage tank and used as first wash of next batch. The herb is checked by Thin Layer chromatography (TLC) for the presence of drug. If it contains less than 50 ppm, the solvent from the rotary extractor is distilled up to 100°C. Then cooled to 60°C and herb is unloaded. The solvent is distilled up to 800 litres residue inside the vessel and cooled to room temperature (RT) and 800 liters of processed water is added. The pH of solution is adjusted to 3.0-3.5 by adding a solution of tartaric acid in water (1: 2). The mixture is stirred for 15-30 min and the content is allowed to settle for 30-60 min in separate layers. The above steps are repeated for second and third time with 400 litres of processed water. The exhausted solvent is then transferred to distillation vessel for solvent recovery. First and second aqueous layers are combined in vessel, treated with activated carbon (1.0 kg), stirred for 30 min and filtered through hyflo bed (celite). The filtrate is collected in a storage tank and transferred to the vessel. The reaction is cooled to 10-20°C and pH is adjusted to 9.0-9.5 with liquor ammonia, stirred for 3-4 hrs and filtered to collect crude wet material of lysergol (5 to 6 kg).
2. Deffating- cum- first acid base treatment
The drug is checked by TLC analysis and impurity should be less than 10% of product. Material is charged in the vessel and processed water (10 times of the bulk) is added. It is stirred for 30 min and pH is adjusted to < 2 with HC1 at RT. Reaction mass is cooled to 15-25°C and stirring is maintained for 2 to 3 hrs. The material is centrifuged, washed with cold water (15-25 litres) and spin dried for 30-60 min. Then the wet material is unloaded, charged in a vessel and processed water 10 times of lysergol wet material is added and pH is adjusted to 9.0-9.5 with liq. Ammonia at RT. The reaction mass is cooled to 15-25°C and stirring is maintained for 2-3 hrs. Material is centrifuged, washed with cold water (15-25 ltr), spin dried for 30- 60 min and unloaded. Slurry washed twice with n-Hexane (25 liters) at RT for defatting and then spin dried and unloaded. Material is charged in a Vacuum Tray dryer and dried for 30-60 min at RT. Hot water is applied and maintained at 35-40°C under vacuum for 2-4 hrs. Material (3.5 to 4.0 kg) is unloaded after terminating heating process. The purity of crude Lysergol is checked by HPLC (the acid base treatment is repeated if impurity is more than 8.0%).
3. Removal of intermolecular water-cum- second acid base treatment
Crude lysergol is placed in glass lined reactor at RT and methanol (7 times of the weight of lysergol) is added .The pH of the methanolic solution of lysergol is adjusted to 5.0-5.4 by adding acetic acid at 35-40°C. It is stirred until the solution becomes clear. Activated carbon (5% weight of lysergol) is added and stirred for 30 min. The solution is filtered through hyflo. The clear filtrate is transferred in a glass lined reactor and cooled to 10-20°C. The pH of the reaction is adjusted by addition of liquor ammonia to 9.0-9.5. The material is filtered and washed with chilled solution of methanol. It is dried under vacuum and lysergol is unloaded. The whole process of purification is repeated once again to obtain pure lysergol.
Finally, lysergol obtained above is transferred to a vacuum tray drier and dried for 30-60 min at room temperature. The steam is applied by maintaining the temperature at 35-40°C under vacuum for 6-8 hrs to remove intermolecular water. The material is unloaded (1.1 to 1.3 kg), ground and sieved using 60-80 mesh size sieve. It has intermolecular water in the ratio of 1: 1 as seen by single crystal diffractometer. Further drying of
lysergol is achieved by crystallizing it from hot ketonic / alcoholic solvent. The lysergol obtained is of 97% purity as estimated by HPLC and having yield of 0.65-0.67%.
In the above detailed description of the invention, method of extracting high purity lysergol has been disclosed. It is to be understood that this invention is not limited to any particular embodiments described as such and these may of course vary. It is also to be understood that the terminology used herein is for the purpose of describing particular embodiments only and is not intended to be limiting, since the scope of the present invention will be limited only by the appended claims.

I CLAIM
1. A process for extracting high purity lysergol from Ipomoea herderacea
comprising the step of
- Extraction for lysergol isolation wherein seeds of Ipomoea herderacea are treated with dichloromethane and methanol in the optimal ratio of 85:15 respectively.
- Defatting- cum- first acid base treatment-1 wherein lysergol obtained is of optimal 92 % purity.
- Removal of intermolecular water-cum- first acid base treatment-2 wherein lysergol obtained is of optimal 97% purity.

2. The process for extracting high purity lysergol from Ipomoea herderacea as claimed in claim 1 during the first stage of purification wherein pH of crude wet material of lysergol is adjusted to less than 2 with HC1 and to 9-9.5 with liquid ammonia at room temperature followed by defatting with n-Hexane.
3. The process for extracting high purity lysergol from Ipomoea herderacea as claimed in claim 1 during the second stage of purification wherein pH of the methanolic solution of lysergol is adjusted to 5.0-5.4 with acetic acid at 35-40°C and to 9-9.5 with liquid ammonia at 10-20°C.
4. The process for extracting high purity lysergol from Ipomoea herderacea as claimed in claim 1 wherein intermolecular water of wet lysergol is removed by maintaining the temperature of steam at 35- 40°C under vacuum for 6-8 hrs.
5. The process for extracting high purity lysergol from Ipomoea herderacea wherein lysergol obtained is of optimal 97% purity.
6. A process for extracting high purity lysergol from Ipomoea herderacea as described substantially herein with reference to the detailed description.