Title of Invention

THE PROCESS OF MANUFACTURE OF PHOSPHATIDYL CHOLINE RICH LECITHIN FROM LECITHINE LIQUID

Abstract

This invention relates to a process for producing Phosphatidyl Choline Rich Lecithin from liquid lecithin comprising following steps; a)subjecting liquid (crude)lecithin to organic solvent in a cylindrical mixer at room temperature with revolution per minute ranging from 200 to 1000; b)decanting the mixture of solvent and Phosphatidyl Choline Rich Lecithin; c)draining reffinate material containing Phosphatidyl ethanol amine and Phosphatidyl inositol rich fraction and subjecting to multiple chilled acetone extraction to get powdered lecithin; d)filtering methanol Phosphatidyl Choline Rich Lecithin in a multiple filter to remove fine particles; e)distlling the mixture ofsolvent and Phosphatidyl Choline Rich Lecithin at 65 to 70ºC at a vacuum of 70 to 750 millimeter of mercury to recover the solvent from mixture; f)cooling at room temperature Phosphatidyl Choline rich Lecithin the product obtained after distillation under vacuum of 750 millimeter of mercury; g)packing the powdered Phosphatidyl Choline Rich Lecithin under asceptic conditions.

Full Text

FORM 2 THE PATENTS ACT, 1970 COMPLETE SPECIFICATION (SECTION 10) THE PROCESS OF MANUFACTURE OF PHOSPHATIDYL CHOLINE RICH LECITHIN FROM LECITHINE LIQUID SONIC BIOCHEM EXTRACTIONS LTD., A Limited Company registered under the Companies Act, 1956, having its office at 38, Patel Nagar, Indore, Madhya Pradesh, India, PIN 452 001. The following specification particularly describes the nature of this invention and the manner in which it is to be performed:- This invention relates to a process of extraction of Phosphatidyl Choline Rich Lecithin from Liquid Lecithin. More particularly the extraction of Phosphatidyl rich Lecithin fraction from Crude Lecithin which is derived from vegetable oil sources like Soyabean, Cotton seed, Rapseed, Corn, Rice Bran, Sunflower seeds, Peanuts etc. Soyabean is a natural crop having multipurpose uses for human beings. It had its origin in China and was developed in India around 1965. Soyabean was primarily developed and grown in India for its high oil content and its uses in improving nitrogen content of land. The crops had a fast growth and the major portion is grown in M.P. accounting for 70% of India"s production and rest developed in Rajasthan and Vidharbh area of Maharashtra. The size of the crop is around 70 lacs tons per year, which yields around 13 lacs tons of Soyabean oil. Soyabean is a natural boon to humanity, it contains oil, proteins, phospholipids, Vitamin E (Tocopherol) and poly unsaturated fatty acids. Till now conventionally in India, Soyabeans are being used mainly for oil extraction and deoiled cake production. Gums and sludge produced during oil refining are not used for any value addition although these contain valuable fractions like Lecithin, Phospholipids. Our R&D unit has developed the process and the technology of extraction of Phosphatidyl Choline rich lecithin from liquid lecithin derived for Soyabean oil gums. Lecithin is a group of naturally occurring phospholipids that"s found in nearly every living cell. Though the word lecithin is derived from the Greek term lekkithos meaning "yolk of an egg", the primary commercial source of lecithin is Soyabean. Lecithin is widely used in manufactured food, feed and pharmaceutical, cosmetic and industrial applications such as crystal formation and antidusting, modifying, emulsilying, dispersing, wetting, penetrating & antioxidising properties. Lecithin is a naturally occurring group of phospholipids, which are important constituents of cell membrane and polyunsaturated fatty acids. Phospholipids: 1) Phosphatidyl Choline (PA) - 23% 2) Phosphatidyl Ethenolamine (PE) - 20% 3) Phosphatidyl Inositol (PI) - 14% 4) Phosphotidic Acid (PA) - 5% 5) Phosphatidyl Serine (PS) - 0.2% Fatty Acid in Soyabean Lecithin: 1) Myristic Acid - 1.5% 2) Palmitic Acid - 18.9% 3) Palmito Oleic Acid - 8.6% 4) Stearic Acid - 3.9% 5) Oleic Acid - 9.8% 6) LivoleicAcid - 20% 7) Linolenic Acid - 2.5% 8) Arachilic Acid - 2.1% The typical composition of phospholipids and fatty acids in lecithin is as under:-A) B) The constitutional formula of Phosphatidyl Choline rich lecithin is as under: - CH2-0-R I CH-OR1 I O I CH20 - P - OR2 I OH Where: R = Fatty Acid R1 = O - P - OR2 - or Fatty Acid OH R2 = CH2-CH2-N (CH3)3 - Phosphatidyl Choline = CH2-CH2-NH3 - Phosphatidyl Ethenolamine = CH2-CH (NH3)-COOH - Phosphatidyl Serine = C6 H6(OH)6 - Phosphatidyl Inositol = H - Phosphotidic Acid Lecithin also contains natural antioxidant as Tocopherol and hence acts as a good antioxidant particularly because of its ability to complex heavy metals. Phosphatidyl Choline is an important constituent of all human cells. As such it plays an important role in the pathophysiology of human disease. The adult human ingests 300 - 1000 mgs. of choline per day. In adult tissue choline levels are significantly increased following ingestion of a choline or lecithin supplemented meal. Choline deficiency has major consequences for many species of animals. It is associated with fatty infiltration liver in the boboon, rat dog, hamster, pig & chicken. Renal function may also be impaired due to membrane lecithin deficiency; Choline deficient animals have abnormal memory, free water absorption, renal plasma flow and gross renal hemorrhaging. Choline deficiency in animals has also been associated with infertility, growth retardation and body abnormalities. Malnourished humans have very low choline concentration in plasma. Supplemental choline can also influence organ function by creasing availability of Choline above normal levels. Choline is a acetyl choline precursor. It is involved in lipid metabolism and acts as methyl doner in various other metabolic processes. Choline has traditionally been considered to be a Vitamin B substance. Acetylcholine is essential for proper brain function. In the brain, choline stimulates the production of Acetylcholine, a neurotransmitter. Neurotransmitters are the chemical messengers that conduct information through the nervous systems bridging the gap between individual neurons and muscle cell. Neurons, tiny nerve cells, control every aspect of behaviour including mood, memory, thought, speech sensation and movement. It is not clear what area acetylcholine targets, but the nervous systems cannot function properly without a sufficient amount of it. Choline obtained from lecithin source enhances operation of the brain and stimulates the brain cells to produce more acetylcholine. Fledging research indicates that the choline from lecithin source may be able to boost memory and counter act depression and dementia traced to deficiency of acetylcholine. Starting results were achieved using choline rich lecithin to treat Tardive Dyskinesia, a disabling brain disorder caused by failure of the brain cells to release acetylcholine. In addition, a study sponsored by Food & Drug Administration (FDA), USA found that taking large dosage of choline chloride or Bitetrate (synthetic product) can lead to nausea, vomiting, salivation, sweating and anorexia and the straight choline was only effective for a short time. Phosphatidyl choline rich lecithin had none of these side effects and proved to be longer acting resistant to bacterial attach and easier to tolerate. Choline deficiency for prolonged periods also lead to hepato carcinomas, a cancer. "FDA authorize claim for Phosphatidyl Choline as Newest Vitamin" Phosphatidyl choline rich lecithin can be used to treat fatty liver and cirrhosis. It can also be used in the treatment of dementia & in various extra pyramidal disorders. According to this invention the process of producing Phosphatidyl choline rich lecithin from liquid lecithin comprises following steps. 1) Subjecting liquid (crude) lecithin to requisite amount of solvent in a specially designed mixer. The solvent is aliphatic alcohols having 1 to 4 carbon atoms. The preferred solvent is methanol. The methanol needs to be dry enough to achieve maximum extraction of Phosphatidyl choline fraction from lecithin. The moisture content or solvent ranges from 0-4%. The moisture content below 1% is preferable. 2) Solvent and liquid lecithin ratio plays important role in extraction. The ratio of solvent to lecithin can be 5:1 or 2:1. The preferred ratio being 3:1. 3) The extraction is carried out in cylindrical mixer having rpm ranging from 200 to 1000 rpm. The preferred rpm being 550 - 600 rpm. The extraction can be carried out at room temperature or 30 - 35°C per hour. For better extraction elevated temperature upto 45°C also proves helpful. 4) Extracted solvent & Phosphatidyl choline rich lecithin mixture is decanted into distillation vessel. The reffinate material, which contains Phosphatidyl Ethenolamine & 7 Phosphatidyl inositol rich fraction is then drained and subjected to multiple chilled acetone extraction to get powdered lecithin. 5) The extracted solvent mixture is then distilled at a temperature of 65 - 70°C at a vacuum of 700 - 750 mm of mercury to recover methanol from the extracts. The methanol choline extract is filtered through a special sparkler filter prior to distillation to remove particulate, if any. 6) Phosphatidyl choline lecithin extract so obtained is then cooled and packed in HDPE drums under asceptic conditions. The Phosphatidyl choline rich lecithin thus obtained meets the following specifications:- 1) Acetone insolubles 50% 2) Phosphatidyl Choline 35% 3) Acid value 30% 4) Moisture 1% 5) Peroxide value 1 6) Gardner colour value 13-14 7) Viscosity at 25°C 5.5 pa.s Prior Art. IN 180994 states : The invention will now be described in greater details giving the various steps of process of the lecithin from the crude lecithin. The crude liquid lecithin from Soyabean oil refineries is fed to a cylindrical mixer, which contains solvent. The proper solvent to lecithin ratio is maintained to achieve maximum extractions of Phosphatidyl choline from lecithin without extracting other phospholipids, like Phosphatidyl ethenol amine, Phosphatidyl inositol. The speed of the rotation of mixing blade is critical. The more the speed more will be the extraction of undesirable phospholipids. The rpm of rotating blades of 550-600 rpm was found to be optimum. The blades were specially designed having perforation in the vanes, to achieve intimate mixing and optimum extraction. The mixing impeller has four blades welded at right angles, each having holes in it. The moisture content of solvent is also important factor here. The moisture content below 1 % is preferable. Methanol solvent is therefore dried through a anhydrous sodium sulphate column to achieve desirable dryness. The ratio of solvent to lecithin is maintained at 3:1. Lower solvent ratio leads to lesser extraction of Phosphatidyl choline and longer extraction time. The raised temperature extraction upto at 45°C reduces the extraction time. Extraction at a temperature of 30-35°C for 1 hour give optimum recovery of Phosphatidyl rich choline lecithin. 8 The solvent and Phosphatidyl rich lecithin mixture is then siphened out in a distillation vessel. The raffinate material, which is rich in Phosphatidyl inositol and Phosphatidyl ethendamine is then drained and converted into powder by multiple extraction with chilled acetone. The extruded solvent mixture is distilled at 65-70 C at vacuum of 700-750 mm of mercury to recover methanol without damaging colour and flavour of the Phosphatidyl choline rich lecithin. It is important to filter to methanol extract in a sparkler filter having multiple filters of 100 mesh to remove the fine particles. The product obtained after distillation is cooled to room temperature under vacuum of 750mm of mercury and packed under asceptic conditions. Example: Process for in rich the Phosphatidyl Choline from mixture of Phosptides Phosotides mixture mainly have Phosphatidyl Choline,Phosphatidyl Ethanolamine,Phosphatidyl Inositol and Phosphatic acid with 40 % oil admixing with solvent .The soluble part of the product have Phosphatidyl Choline, Phosphatidyl Ethanolamine,Phosphatidyl Inoositol and oil. The insoluble part have Phosphatidyl,Ethanolamine Phosphatic acid, and oil. The separation of soluble & insoluble is depends proper time of setting & solvent taken like Methanol Isopropanol Ethanol etc.The influence can be clearly seen of the water content in the solvent on the distribution of the accompanying triglycerides between soluble and insoluble fractions. Experiment 01. 1. Take 100gm. Of Phosptides mixture admix with 300 ml. Of 100% Methanol. 2. Mix for 30 min. at temp. 50"c settle the material. 3. Seprat settle material top layer distill under vaccum. 4. Top layer distill under vaccum. 5. Check yield & % of Phosphatidyl Choline on HPLC. Initial Phosphatidyl Choline After treatment with 100% Mthanol Phosphatidyl Choline% Yield 18% 24% 22% Experiment 02. 1. Take 100gm. Of Phosptides mixture admix with 300 ml. Of 100% Isopropanol. 2. Mix for 30 min. at temp. 50"c settle the material. 3. Seprat settle material top layer distill under vaccum. 4. Top layer distill under vaccum. 5. Check yield & % of Phosphatidyl Choline on HPLC. Initial Phosphatidyl Choline After treatment with 100% Isopropanol Phosphatidyl Choline% Yield 18% 21% 23% Experiment 03. 1. Take 100gm. Of Phosptides mixture admix with 300 ml. of 100 % Ethanol. 2. Mix for 30 min. at temp. 40"c settle the material. 3. Seprat settle material top layer distill under vaccum. 4. Top layer distill under vaccum. 5. Check yield & % of Phosphatidyl Choline on HPLC. Initial Phosphatidyl Choline After treatment with 100% Ethanol Phosphatidyl Choline% Yield 18% 28% 24% Experiment 04. 1. Take 100gm. Of Phosptides mixture admix with 300 ml. Of 95% Ethanol. 2. Mix for 30 min. at temp. 50"c settle the material. 3. Seprat settle material top layer distill under vaccum. 4. Top layer distill under vaccum. 5. Check yield & % of Phosphatidyl Choline on HPLC. Initial Phosphatidyl Choline After treatment with 95 % Ethanol Phosphatidyl Choline% Yield 18% 35% 21% Experiment 05. 1. Take 100gm. of Phosptides mixture admix with 300 ml. of 90% Ethanol. 2. Mix for 30 min. at temp. 50"c settle the material. 3. Seprat settle material top layer distill under vacuum. 4. Top layer distills under vacuum. 5. Check yield & % of Phosphatidyl Choline on HPLC. Initial Phosphatidyl Choline After treatment with 90 % Ethanol Phosphatidyl Choline% Yield 18% 40% 15% CONCLUSION :- 1. Temp, is not playing important role. 2. Water contents the enrich the phosphatidyl choline % but yield is effected. 3. Distillation is done under vacuum. 4. Material separations is an important step. 5. phosphatidyl choline % is higher with 95 % Ethanol. Methanol and Isopropanol solvent are not so effective. In this process, high efficiency chillers and efficient solar heating system is used to maintain operating parameters. CLAIM 1. A process for producing Phosphatidyl Choline Rich Lecithin from liquid lecithin comprising following steps; a) subjecting liquid (crude) lecithin to organic solvent in a cylindrical mixer at room temperature with revolution per minute ranging from 200 to 1000; b) decanting the mixture of solvent and Phosphatidyl Choline Rich Lecithin; c) draining reffinate material containing Phosphatidyl ethanol amine and Phosphatidyl inositol rich fraction and subjecting to multiple chilled acetone extraction to get powdered lecithin; d) filtering methanol Phosphatidyl Choline Rich Lecithin in a multiple filter to remove fine particles; e) distilling the mixture of solvent and Phosphatidyl Choline Rich Lecithin at 65 to 70°C at a vacuum of 70 to 750 millimeter of mercury to recover the solvent from mixture; f) cooling at room temperature Phosphatidyl Choline rich Lecithin the product obtained after distillation under vacuum of 750 millimeter of mercury; g) packing the powdered Phosphatidyl Choline Rich Lecithin under asceptic conditions. 2. A process of producing Phosphatidyl Choline Rich Lecithin as claimed in claim (1), wherein the organic solvent is selected from aliphatic alcohol having 1 to 4 carbon atoms; preferably methanol. 3. A process of producing Phosphatidyl choline Rich Lecithin as claimed in claim (1), wherein moisture content of the solvent is from 0 to 4% preferably below 1%. 4. A process of producing Phosphatidyl Choline Rich Lecithin as claimed in claim (1), wherein the ratio of solvent to liquid lecithin is 5:1 to 2:1, preferably 3:1. 5. A process of producing Phosphatidyl Choline rich Lecithin as claimed in claim (1), wherein the revolution per minute of cylindrical mixture is preferably from 550 to 600. 6. A process of producing Phosphatidyl Choline rich Lecithin as claimed in claim (1), wherein the extraction temperature is room temperature preferably below 45°C. 7. A process of producing Phosphatidyl Choline rich Lecithin as herein before described in this complete specification. SHRIKISHAN CHOITHRAM MATLANI MANAGING DIRECTOR Dated: 14.10.2004 For SONIC BIOCHEM EXTRACTIONS LTD. 19

Documents:

1094-mum-2004 claims(14-10-2004).pdf

1094-mum-2004 claims.pdf

1094-mum-2004 description(granted).pdf

1094-mum-2004 form 1(superceded).pdf

1094-mum-2004 form 1.pdf

1094-mum-2004 form 19.pdf

1094-mum-2004 form 2(complete specification).pdf

1094-mum-2004 form 2(granted).pdf

1094-mum-2004 form 2(title page).pdf

1094-mum-2004 form 3.pdf

1094-mum-2004 u.s.patent.pdf

1094-mum-2004-cancelled page-(14-1-2005).pdf

1094-mum-2004-claims(granted)-(14-1-2005).doc

1094-mum-2004-claims(granted)-(14-1-2005).pdf

1094-mum-2004-claims.doc

1094-mum-2004-correspondence(7-3-2005).pdf

1094-mum-2004-correspondence(ipo)-(28-12-2005).pdf

1094-mum-2004-description(granted).doc

1094-mum-2004-form 1(14-1-2005).pdf

1094-mum-2004-form 1(14-10-2004).pdf

1094-mum-2004-form 19(14-10-2004).pdf

1094-mum-2004-form 2(granted)-(14-1-2005).doc

1094-mum-2004-form 2(granted)-(14-1-2005).pdf

1094-mum-2004-form 2(granted).doc

1094-mum-2004-form 3(14-10-2004).pdf