WO2014178081A2 - Molecular traps for certain undesirable materials - Google Patents

Molecular traps for certain undesirable materials Download PDF

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Publication number
WO2014178081A2
WO2014178081A2 PCT/IN2014/000288 IN2014000288W WO2014178081A2 WO 2014178081 A2 WO2014178081 A2 WO 2014178081A2 IN 2014000288 W IN2014000288 W IN 2014000288W WO 2014178081 A2 WO2014178081 A2 WO 2014178081A2
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mip
molecularly imprinted
polymer
palmitic acid
mips
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PCT/IN2014/000288
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French (fr)
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WO2014178081A3 (en
Inventor
Laxmikant Niranjan BARDE
Vijay Bhagwanswarup MATHUR
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Zim Laboratories Limited
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Publication of WO2014178081A3 publication Critical patent/WO2014178081A3/en

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    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00Medicinal preparations characterised by special physical form
    • A61K9/14Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/74Synthetic polymeric materials
    • A61K31/765Polymers containing oxygen
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00Medicinal preparations characterised by special physical form
    • A61K9/0012Galenical forms characterised by the site of application
    • A61K9/0053Mouth and digestive tract, i.e. intraoral and peroral administration

Definitions

  • the present invention relates to molecular traps or molecularly imprinted polymers (MIPs) for reducing the amount of undesirable materials consumed orally (through food) from getting absorbed by a living body in the digestive tract. Further, the present invention relates to composition for oral administration and processes for the preparation of the same comprising said MIPs having selective trapping capability of undesirable materials consumed through food from getting absorbed by a living body in the digestive tract. Also, the MIPs according to the present invention are used for above purpose to reduce the risk of various diseases, poisoning or medical complications caused because of the probable absorption of the relevant undesirable material/s.
  • a Molecularly Imprinted Polymer is a polymer that has been processed using the molecular imprinting technique which leaves cavities in polymer matrix with affinity to a chosen "template” molecule.
  • the process generally involves initiating the polymerization of monomers in the presence of a chosen template molecule that is extracted afterwards and leaves complementary cavities behind.
  • These polymers have affinity for the original molecule and have been used in applications like chemical separations, catalysis, or molecular sensors (Byrne ME, Salian V. Molecular imprinting within hydrogels II: Progress and analysis of the field. Int J Pharm 2008;364(2): 188-212. Alvarez-Lorenzo C, Concheiro A. Molecularly imprinted polymers for drug delivery. J Chromatogr B 2004;804: 231 -45. Wulff G, Sarhan A. Use of polymers with enzyme- analogous structures for the resolution of recemates. Angew. Chem Int Ed. 1972; 1 1 : 341-42).
  • MIPs are stable macromolecular networks characterized by specific recognition sites for a desired target molecule. Literature also reveals that majority of work using MIPs has been done on separation, extraction and detection of specific bodies using chromatography and solid phase extraction.
  • NIP Non imprinted polymer
  • molecularly imprinted polymers have been applied in several analytical techniques, such as liquid chromatography, capillary electrochromatography and capillary electrophoresis, solid phase extraction, immunoassay, and as a selective sorbent in chemical sensors.
  • MIPs as selective sorbents in capillary electrochromatography
  • Molecular imprinting developments and applications in the analytical chemistry field. J of Chromato B, 745 (2000) 3-13
  • the use of MIPS as stationary phases for HPLC is further example in anlyticla chemistry.
  • MISPE Molecular-imprint based solid-phase extraction
  • MIPs have been used for selective solid-phase extraction for the analysis of polar organophosphorus pesticides (monocrotophos, mevinphos, phosphamidon, omethoate) in water and soil samples.
  • the MIPs enabled the selective extraction of four organophosphorus pesticides successfully from water and soil samples, demonstrating the potential of molecularly imprinted solid-phase extraction for rapid, selective, and cost- effective sample pretreatment (Zhu X et al 2005).
  • Piletsky SA Parhometz YP, Lavryk NV, Panasyuk TL,Elskaya AV. 1994. Sensors for low-weight organicmolecules based on molecular imprinting technique. Sens. Actuators B 19: 629-631. Piletskii SA, Kurys YI, Rachkov AE, Elskaya AV. 1994. Formation of matrix polymers sensitive to aniline and phenol. Russ. J. Electrochem. 30: 990-992.]
  • the present invention provides composition for oral administration comprising specific MIP(s) for reducing the amount of undesirable material consumed orally through food being absorbed in the living body through digestive tract.
  • the primary object of the present invention is to provide molecular traps or molecularly imprinted polymers (MIPs) for reducing the amount of undesirable materials consumed orally (through food) from getting absorbed in the digestive tract by a living body by oral administration of MIPs.
  • MIPs molecular traps or molecularly imprinted polymers
  • Another object of the present invention is to provide process for preparation of MIPs used for treatment of various diseases, poisoning or medical complications caused because oi absorption of undesirable materials in the digestive tract.
  • Still another objective of present invention was to provide MIPs specific for palmitic acid, a process to produce them. Further, the objective also was to provide compositions containing MIPs specific for palmitic acid for oral consumption so as to reduce the absorption in the digestive tract of palmitic acid from context of the digestive tract.
  • This invention comprises a process/method of using oral administration of a composition of Molecularly imprinted polymers (MIPs) imprinted with one or more of undesirable material/s for reducing the amount of one or more of the undesirable material/s being absorbed from the digestive tract of a living body. It is an embodiment of this invention that the Molecularly Imprinted Polymers in the compositions have capability of trapping specific undesirable material/s from food in the digestive tract of a living body.
  • MIPs Molecularly imprinted polymers
  • the oral administration of the composition of MIP is done, either by consuming (a) a food in which MIP/s is/are incorporated/involved in the food, or (b) a tablet containing the MIP and the food, or (c) a sachet of MIP containing composition and the food, or (d) a fluid to which a composition of MIP/s is added and the food.
  • the composition of MIP/s comprises (a) single molecularly imprinted polymer or a combination of molecularly imprinted polymers, and (b) optionally is combined with excipients; and is one of the embodiments of the instant invention.
  • the excipients comprise one or more selected from the group of a binder, diluents, disintigrant, glidant and lubricant.
  • composition of the Molecularly Imprinted Polymer may have one or more molecularly imprinted polymers in the range of between 200 - 700mg, binder/s in the range of 2 - 5%, diluents/s in the range of 5 - 20%, disintegrant/s in the range of 2 - 3%, glidant/s in the range of 1 - 2% and lubricant/s in the range of 1 - 5%
  • the invention is also embodied in a processes for the preparation of specific molecularly imprinted polymer as claimed in claim 1, comprising steps of: (a) dissolving a template specific for an undesirable material in a solvent, wherein the undesirable material is a material that is needed to be totally or partly prevented from absorption in the digestive tract, (b) adding a monomer and crosslinker, (c) bubbling nitrogen gas, (d) heating the mixture, (e) dissolving the initiator in minimum quantity of solvent, (f) carrying out the polymerization at an elevated temperature for a time wherein the temperature and time is selected to facilitate completion of polymerization and obtaining polymer complex, (g) filtering the polymer complexes, washing with solvent, drying, grinding the dried polymer complex and sieving, (h) releasing of template from polymer complex by suspending the polymer complex in solvent under constant stirring at speed, temperature and time effective for achieving release of the template from the polymer, (i) After the template release from polymer complex, polymer complex was again kept in pH 5 -
  • the specific template molecule is selected one or more from the group consisting of glucose, pesticides, palmitic acid or other fatty acids, monocrctophos or any other molecule needed to be prevented or reduced from being absorbed in the digestive tract,
  • the process/method of this invention comprising using/use of oral administration of a composition of Molecularly imprinted polymers (MIPs) specific for trapping one or more undesirable materials comprises a means to reduce the risk of or for preventing various diseases, poisoning or medical complications caused because of respective undesirable materials.
  • MIPs Molecularly imprinted polymers
  • this invention comprises a molecularly imprinted polymer having specific capability of binding/trapping palmitic acid.
  • This invention also comprises a process for the preparation of palmitic acid specific molecularly imprinted polymer comprising following steps: (a) accurately weighing palmitic acid as template, (b) dissolving palmitic acid in chloroform in a container/reactor equipped with a stirrer, a reflux condenser and a nitrogen inlet, (c) adding monomer 2- hydroxy ethyl methacrylate (HEMA) and crosslinker ethylene glycoldimethacrylate (EGDMA) and bubbling nitrogen gas for removal of atmospheric oxygen until a homogeneous mixture is formed, (d) heating the mixture to an elevated temperature, dissolving by adding azobisisobutyronitrile (AIBN) dissolved in minimum quantity of chloroform, and carrying out polymerization by maintaining the temperature at the elevated temperature, for a period of time to complete the polymerization, (d) filtering the polymer complex formed,
  • a molecularly imprinted polymer of claim 13 having specificity to trap palmitic acid in a polymer matrix derived from polymerization of monomer 2- hydroxy ethyl methacrylate (HEMA) with a crosslinker ethylene glycoldimethacrylate (EGDMA).
  • HEMA monomer 2- hydroxy ethyl methacrylate
  • EGDMA crosslinker ethylene glycoldimethacrylate
  • This invention is also embodied in a composition of Molecularly imprinted Polymer comprising a molecularly imprinted polymer and excipients,
  • the excipients may comprise, one or more selected from the group of binder, diluents, disintigrents, glidants and lubricants.
  • the composition of the Molecularly imprinted Polymer may be a tablet or a powder.
  • the powder may be filled in sachets.
  • this invention comprises a process/method of reducing the amount of one or more of undesirable material/s being absorbed from the digestive tract of a living body comprising a step of oral administration of a composition of Molecularly imprinted polymers (MIPs) imprinted with the undesirable material/s.
  • MIPs Molecularly imprinted polymers
  • the present invention provides specific MIPs which are used for reducing the amount of specific undesirable materials consumed orally (through food) from getting absorbed from the digestive tract of a living body. Absoiption in the digestive tract of living body of undesirable materials such as glucose (for patients suffering from Diabetes mellitus (Type- 2 Diabetes)); harmful pesticides (present in fruits and vegetables and which causes toxicity); fatty acids like palmitic acid (for patients suffering from moderate to high cholesterol problems); etc., can be reduced getting absorbed from digestive tract of a living body by use of the MIPs specific for the respective/relevant undesirable material. Further, the present invention provides processes for the manufacture of undesirable material specific MIPs which are used for reducing the amount of undesirable materials absorbed from digestive tract of a living body. Also, according to the present invention, composition for oral administration comprising specific MIPs is disclosed which are used for reducing the amount of specific undesirable materials being absorbed from digestive tract of a living body.
  • molecular traps or molecularly imprinted polymers are prepared for reducing the amount of undesirable materials absorbed from a living body by oral administration of MIPs.
  • novel composition is prepared by a novel processes for the preparation of the same using said MIPs having selective trapping capability of undesirable materials from a living body.
  • this invention also comprises use of MIPs for treatment or prevention or reducing the risk of various diseases, • poisoning or medical complications caused because of various undesirable materials.
  • MIP a polymer that has been processed/prepared using the molecular imprinting technique, which leaves cavities in polymer matrix with affinity to a chosen "template” molecule, wherein the process generally involves polymerization of monomers in the presence of a chosen template molecule which is extracted afterwards and leaves complementary cavities behind which can be upto micro or nano cavities.
  • Now prepared polymers can be used in applications like chemical separations, catalysis, or molecular sensors.
  • the present invention discloses MIPs and composition using MIPs.
  • the processes for the preparation of specific MIPs require specific template molecule, functional monomer(s), crosslinking agent(s), an initiator and solvents.
  • the template molecule should be chemically inert under the polymerization condition. It is observed that, in general, small, multi-functional, template molecules give rise to highly specific imprints whilst larger, mono-functional template molecules produce imprinted sites which have less specificity. According to the present invention, the specific unwanted material the absorption of which is required to be reduced from the digestive tract is selected as specific template for making MIP specific for the same.
  • template molecules are specific undesirable materials such as, including but not limited to, glucose, pesticides, fatty acids like palmitic acid, etc for which specific MIPs are prepared.
  • Template molecule is of central importance as it directs the organization of the functional groups dependent to the functional monomers.
  • monomers used for preparation of polymers can be selected from the group including but not limited to methacrylic acid, acrylic acid and hydroxyethylmethacrylate, 4 Vinyl pyridine, 2 vinyl pyridine, allyl amine, Acrylamide, methacrylamide, acrylonitrile, methyl methacrylate, styrene, ethylstyrene, 2- (trifluromethyl)-acrylic acid etc
  • Polymers undergo regiospecific, weak, complementary, interaction with a particular moiety of the template molecule.
  • the polymers contain a polymerizable unit.
  • crosslinking agents are used to fix the guest-binding sites firmly in the desired structure of MIPs.
  • Crosslinking agents make the MIPs insoluble in solvents and facilitate their practical applications as disclosed in the present invention. Different kinds of crosslinking agents can be used to control both the structure of the guest-binding sites and the chemical environments around them for efficient imprinting process.
  • Crosslinking agent used in the preparation of MIPs based on polymer can be selected from the group including but not limited to ethylene glycol dimetacrylate (EGDMA) divinyl benzene, l ,3,diisopropenyl benzene, tetra methylenedimethacrylate, trimethyl propane trimethacrylate, pentaerythritotriacrylate, pentaerythritoltetracrylate, NN-methylene bismethacrylamide, NN-ethylene bismethacrylamide, and the like.
  • EGDMA ethylene glycol dimetacrylate
  • Glucose Methacrylic acid (monomer), acrylic acid 4 Vinyl pyridine, 2 vinyl pyridine, allyl amine, and EGDMA (crosslinking agent), l,3,diisopropenyl benzene,tetramethylenedimethacrylate,trimethylpropanetrimethacrylate ...2- hydroxy ethyl methacrylate, divinyl benzene; b.
  • Monocrotophos - Acrylic acid (monomer), methacrylic acid, 2-hydroxy ethyl methacrylate 4 Vinyl pyridine, 2 vinyl pyridine, and EGDMA (crosslinking agent) ;,Divinylbenzene, l,3,diisopropenylbenzene, tetra methylenedimethacrylate, 2-hydroxy ethyl methacrylate;
  • Initiators are used as the radical source in free radical polymerization. Polymerization initiate through liberation of nescent oxygen. It should be soluble in solvent.
  • the initiator can be selected from the group but not limited to azobisisobutriyonitrile, benzyl peroxide, azobisdimethylvaleronitrile, dimethylacetalof benzene.
  • the solvents can be selected but not limited to water, chloroform, methanol,, ethanol, Butanol, Isopropyl alcohol, benzene, tolune, xylene, dimethylsulpoxide, and the like.
  • polymerization solvent solubilizes all the monomer in the pre-polymerization mixture before polymerization, it stabilizes the template monomer pre-polymerization complex, it acts as a porogen helping to control the porosity of resulting polymer.
  • MIPs of this invention Following methods for the preparation of the specific MIPs can be used to make MIPs of this invention: a) Self-assembly method, which involves the formation of polymer by combining all elements of the MIP and allowing the molecular interactions to form the cross- linked polymer with the template molecule bound. b) The second method of formation of MIPs involves covalently linking the imprint molecule to the monomer. After polymerization, the monomer is cleaved from the template molecule.
  • MIPs prepared according to the above processes are generally opaque, vitreous and brittle in nature. MIPs should be reduced to a fine particulate material of uniform particle size. Typically, this is achieved by grinding processes or by mechanical means. MIPs are then sieved to give a powder of fixed upper particle size (25-45 ⁇ ).
  • prepared MIPs are non-toxic and useful for removal of residual toxin, toxic material from food in the digestive tract to prevent or reduce the risk of medical disorders and many diseases.
  • this invention is embodied in a novel composition of specific MIPs for oral administration which are used for reducing the amount of specific undesirable materials being absorbed from the digestive tract in a living body.
  • Said composition of MIPs comprises of either specific MIPs only or the said composition comprises specific MIPs and at least one another pharmaceutically acceptable excipient.
  • the said pharmaceutically acceptable excipient may include but not restricted to binders, diluents, disintegrants, glidants, lubricants, etc.
  • the said compositions of specific MIPs can be dispensed as such in powder form which can be sprinkled over or incoiporated in foods, dispensed in sachets, consumed directly with fluid (e.g. water), filled in capsules, or dispensed / compressed as tablets.
  • Binders can be selected from the group including but not limited to, Starch paste and PVP- 30.
  • Diluents can be selected from the group including but not limited to, Starch, lactose , Microcrystalline cellulose and Dibasic calcium Phosphate.
  • Disintegrants can be selected from the group including but not limited to, Sodium starch glycolate, Sodium lauryl sulphate, cross carmalose sodium, cross-providone, dry starch.
  • Glidants can be selected but not limited to, Talc and magnesium stearate.
  • Lubricants can be selected from the group including but not limited to talc, magnesium
  • the composition may comprise single MIP or combination of MIPs.
  • compositions of MIPs used here contain “excipients".
  • excipients shall be understood as substances that makes the composition suitable for and meant for oral consumption as a means for capturing undersirable substances in the digestive tract and preventing or reducing their absorption in the living body through the digestive tract.
  • excipients are the substances that make the MIPs associated with them a composition that is not meant for analytical, diagnostic or sensory purposes.
  • excipients point out to ingredients which are edible and the resulting composition shall be a pharmaceutical composition or a composition that can be consumed with food, hence entirely different than the compositions of MIPs which are meant for analytical, diagnostic or sensory purposes.
  • the present invention is illustrated but is not limited in any way by following examples, and modifications thereto falling within the scope and spirit of the appended claims and which would be obvious to a person skilled in the art based upon the disclosure herein, are also considered to be included within the scope of this invention.
  • Polymerization was carried out by maintaining the temperature at 40 - 70°C for 7 - 12 hours.
  • MIPs prepared according to the above processes are generally produced are opaque, vitreous and brittle in nature. MIPs should be reduced to a fine particulate material of uniform particle size. Typically, this is achieved by grinding processes or by mechanical means. MIPs are then sieved to give a powder of fixed upper particle size (25-45 ⁇ ). Using the above MIP a novel composition is prepared for oral administration.
  • Novel composition of moiecularly imprinted polymer comprises molecularly imprinted polymer between 200 - 700mg, binder 2 - 5%, diluents 5 - 20%, disintigrent 2 - 3%, glidant 1 - 2%, lubricant I - 5%
  • Example 1.2 Process for preparation of Palmitic acid specific MIP: Accurately weighed quantity of palmitic acid as template was dissolved in chloroform in a four necked round bottom 250 mL capacity flask equipped with a stirrer, a reflux condenser and a nitrogen inlet. To this, monomer 2- hydroxy ethyl methacrylate (HEMA) and crosslinker ethylene glycoldimethacrylate (EGDMA) were added and nitrogen gas was bubbled for 30 min. The mixture was heated to 60°C and azobisisobutyronitrile (AEBN) dissolved in minimum quantity of chloroform was added and polymerization was carried out by maintaining the temperature at 60"C for further 12 h. Polymer was filtered, washed with chloroform and dried. This was subsequently grounded in a mortar-pestle and passes through #16 and retained on retained on 40.
  • HEMA monomer 2- hydroxy ethyl methacrylate
  • EGDMA crosslinker ethylene glycoldime
  • the palmitic acid release was carried out in 100 mL volumetric flask (stoppered) using polymer complex 1 g in 100 mL of chloroform.
  • the volumetric flask assembled on a magnetic stirrer for constant stirring (50 rpm). Aliquots of 1 mL was withdrawn at specific time intervals (1 h) and analyzed by UV-Vis spectrophotometer for palmitic acid content at 440 nm.
  • Example 2 Process for preparation of a formulation/composition containing MIPs
  • prepared granules/MIP powder can be sprinkled over or involved/incorporated in foods, dispensed in sachets, consumed directly with fluid (e.g. water), filled in capsules, or dispensed / compressed as tablets as per the required dose.
  • Ihe dosages are used for in-vitro and in-vivo studies.
  • MIP(s) are compared with NIP. The results showed that while MIPs were capable of binding with respective undesired materials or capturing them, NIPs were not able to appreciably bind with or capture the undesirable materials. Thereafter the MIP(s) formulations were studied in-vivo.
  • a non imprinted polymer was prepared exactly the same way as the MIP, but in the absence of the template.
  • Diabetic rats were further assigned randomly to following groups (each group contains six animals).
  • Group I - Normal rats received vehicle solution normal saline and glucose 3 g/kg of body weight
  • the blood glucose level was 231.50 mg/dL. After 1 , 2 and 5 h the blood glucose level was 334.67, 285.30 and 229.17 mg/dL respectively.
  • High fat diet cocktail was prepared by mixing cholesterol, cholic acid in 1 liter of coconut oil. The animals were fed a high-cholesterol diet for 10 days. To confirm the induction of hyperlipidemia, blood samples were collected by retro orbital puncture. The total cholesterol (TC) concentration of the blood samples was then determined using a standard diagnostic kit (span diagnostic) by Biochemical autoanalyser (Star 21). The rats were then divided into 4 groups of 6 animals based on their cholesterol levels, after which the treatments were administered orally twice a daily for 10 days. Hyperlipidemic rats were further assigned randomly to following groups (each group contains six animals).
  • TG, LDL and HDL level was 174.03 mg/dL, 153.98 mg/dL, 85.93 mg/dL and 17.38 mg/dL respectively.
  • group III HFD control treated with Simvastatin 10 mg/kg at 10th day TC, TG, LDL and HDL level was 104.85 mg/dL, 89.08 mg/dL, 41.15 mg/dL and 31.81 mg/dL respectively.
  • palmitic acid from pea nut oil absorbed by MIP was 7.99% in 2h and 10.30% in 8h, while palmitic acid from safflower oil absorbed by MIP was 3.39% in 2h and 4.40% in 8h.
  • MIP molecularly imprinted polymer
  • MIP of ( 1 g) suspended in 50 mL containing monocrtophos ( 1 g) and monocrotophos (0.5 g) plus mevinphos (0.5 g) solution was kept for 8 h under stirring. From this solution, 0.1 mL of sample was withdrawn at specified time interval and analyzed by UV-Vis spectrophotometer for balance quantity of monocrotophos remained in solution and calculated for monocrotophos uptake by MIP.
  • the monocrotophos absorbed by MIP from monocrotophos solution was 26.62% in 2 h and 29.30%) in 8 h and in case of mixture absorption of monocrotophos was 53.14% in 2 h and 58.56%) in 8 h respectively.

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Abstract

This invention comprises composition of and a process/method of using oral administration of a composition of Molecularly imprinted polymers (MIPs) imprinted with one or more of undesirable material/s for reducing the amount of one or more of the undesirable material/s being absorbed from the digestive tract of a living body. The MIPs in the compositions have capability of trapping specific undesirable material/s from food in the digestive tract of a living body. This invention also comprises a MIP specific for palmitic acid. In Vivo and InVitro Illustrations have been given for reduction in absorption in glucose and palmitic acid; and InVitro illustration for monocrotophos specific MIP and its specificity. The MIPs are consumed by oral administration of the MIPs or compositions containing MIP, either by consuming (a) a food in which MIP/s is/are incorporated/involved in the food, or (b) a tablet containing the MIP and the food, or (c) a sachet of MIP containing composition and the food, or (d) a fluid to which a composition of MIP/s is added and the food. The undesirable material may be an undesired nutrient, an undesired food ingredient, a pesticide/pesticide residue, a poison, bacteria, viruses or cells.

Description

TITLE
MOLECULAR TRAPS FOR CERTAIN UNDESIRABLE MATERIALS FIELD OF THE INVENTION
The present invention relates to molecular traps or molecularly imprinted polymers (MIPs) for reducing the amount of undesirable materials consumed orally (through food) from getting absorbed by a living body in the digestive tract. Further, the present invention relates to composition for oral administration and processes for the preparation of the same comprising said MIPs having selective trapping capability of undesirable materials consumed through food from getting absorbed by a living body in the digestive tract. Also, the MIPs according to the present invention are used for above purpose to reduce the risk of various diseases, poisoning or medical complications caused because of the probable absorption of the relevant undesirable material/s.
BACKGROUND OF THE INVENTION
A Molecularly Imprinted Polymer (MIP) is a polymer that has been processed using the molecular imprinting technique which leaves cavities in polymer matrix with affinity to a chosen "template" molecule. The process generally involves initiating the polymerization of monomers in the presence of a chosen template molecule that is extracted afterwards and leaves complementary cavities behind. These polymers have affinity for the original molecule and have been used in applications like chemical separations, catalysis, or molecular sensors (Byrne ME, Salian V. Molecular imprinting within hydrogels II: Progress and analysis of the field. Int J Pharm 2008;364(2): 188-212. Alvarez-Lorenzo C, Concheiro A. Molecularly imprinted polymers for drug delivery. J Chromatogr B 2004;804: 231 -45. Wulff G, Sarhan A. Use of polymers with enzyme- analogous structures for the resolution of recemates. Angew. Chem Int Ed. 1972; 1 1 : 341-42).
MIPs are stable macromolecular networks characterized by specific recognition sites for a desired target molecule. Literature also reveals that majority of work using MIPs has been done on separation, extraction and detection of specific bodies using chromatography and solid phase extraction.
Various aspects of methods of preparation of MIPs have been described in the literature.
Several monomers and cross-linking agents are described useful for preparation of polymers for making MIPs have been described by Breton et al (Breton F, Rouillon R, Piletska EV, Karim K, Guerreiro A, Chianella I, Piletsky SA. Virtual imprinting as a tool to design efficient MIPs for photosynthesis-inhibiting herbicides. Biosensors and Bioelectronics 2007;22: 1948-54.)
Various initiators have been described by Hongyuan et al that are useful as the radical source in free radical polymerization (Hongyuan Y, yung R. Characteristic and synthetic approach of molecularly imprinted polymer. Int J Mol Sci 2006; 7: 155-78). omiyama et al have described various solvents that can be used for making MIPs (Komiyama M, Takeuchi T, Mukawa T, Asanum H. Fundamentals of Molecular Imprinting. In: Molecular Imprinting-from fundamental to applications. 2003. Wiley- VCH Verlag GmbH & Co. GaA, Weinheim, pp. 24-25) and have pointed out to multiple roles solvents in the process of making MIPs. Methods of making specific MIPs are also give in details by Mosbach et al (Mosbach K, Ramstrom O. The emerging technique of molecular imprinting and its future impact on biotechnology. Bio/Technology 1996; 14: 163-70.) and Komiyama et al ( omiyama M, Takeuchi T, Mukawa T, Asanum H. Fundamentals of Molecular Imprinting. In: Molecular Imprinting-from fundamental to applications. 2003. Wiley- VCH Verlag GmbH & Co. KGaA, Weinheim, pp. 9-19).
The Non imprinted polymer (NIP) are prepared exactly in the same manner as the MIP, but in the absence of the template.
William J et al. (Biomaterials 2001 ;22: 1485-91 ) developed molecularly imprinted polymer hydrogels displaying isomerically resolved glucose binding by using poly (allylamine hydrochloride) as a functional monomer, glucose phosphate mono-sodium salt as a template, epichlorohydrin, ethylene glucol diglycidyl ether, and glycerol diglycidyl ether as crosslinkers and AIBN as a catalyst. They concluded that molecular imprinting procedure presented in this work is the first attempt at molecular imprinting in aqueous solution using a polymer and crosslinkers rather than functional monomer.
Cheng Z et al. (Biosens. Bioelectron 2001 ; 16: 179-85) reported capacitive detection of glucose using molecularly imprinted polymers. The sensitive layer was prepared by electropolymerization of o-phenylenediamine on a gold electrode in the presence of the template (glucose). Hwang CC et al. (J Chromatogr A 2002;962: 69-78) prepared cholesterol imprinted polymers by covalent and non-covalent imprinting methods and studied its chromatographic characters. MIPs could provide an alternative approach to create receptor like binding sites. In this technology complexes between imprinting molecules (templates) and functional monomer are allowed to self assemble in solution and subsequently the three dimensional structure of these complexes are formed by polymerization with a high degree of cross linking. This can be achieved if the target is present during the polymerization process, thus acting as a molecular template. Monomers carrying certain functional groups are arranged around the template through either non-covalent or covalent interactions. Following polymerization with a high degree of cross-linking, the functional groups are held in position by the polymer network. Subsequent removal of the template by solvent extraction or chemical cleavage leaves cavities that are complementary to the template in terms of size, shape and arrangement of functional groups. These highly specific receptor sites are capable of rebinding the target molecule with a high specificity.
Despite the current good potential prospective uses of molecular imprinting, no molecularly imprinted product has reached the market yet, That some commercial interest existed is also confirmed by the fact that Sigma Aldrich produces supel MIP for beta-agonist, beta-blockers, pesticides and some drugs of abuse such as amphetamine. T. L. Delaney, D. Zimin, M. Rahm, D. Weiss, O. S. Wolfbeis, V. M. Mirsky. "Capacitive detection in ultrathin chemosensors prepared by molecularly imprinted grafting photopolymerization". Analyt. Chemistry, 2007, 79, 3220-3225 describes that Fast and cost-effective molecularly imprinted polymer technique has applications in many fields of chemistry, biology and engineering, particularly as an affinity material for sensors, and Lok, CM; Son, R. (2009). "Application of molecularly imprinted polymers in food sample analysis - a perspective"
International Food Research Journal 16: 127-140 describes uses that includes detection of chemical, antimicrobial, dye, residues in food, adsorbents for solid phase extraction, binding assays, artificial antibodies, chromatographic stationary phase, catalysis, drug development and screening, and byproduct removal in chemical reaction.
Allender, C. J., Richardson, C, Woodhouse, B., Heard, C. M., and Brain, K. R. Int. J. Pharrn. 2000 195 39 describes that the capability for MIP(s) to be a cheaper easier production of antibody/enzyme like binding sites makes this technique as a valuable breakthrough in medical research and application. Such and other possible medical applications include "controlled release drugs, drug monitoring devices, and biological receptor mimetics".
The MIPs of glucose are reported for the application of chromatographic separation, isolation and sensor by various workers including the following:
1 ) P. Parmpi, P. Kofinas; Biomimetic glucose recognition using molecularly imprinted polymer hydrogels; Biomaterials 25 (2004) 1969-1973.
2) Wizeman WJ, Kofinas P., Molecularly imprinted polymer hydrogels displaying isomerically resolved glucose binding, Biomaterials. 2001 Jun;22(12): 1485-91.
3) Seong H, Lee HB, Park KJ Glucose binding to molecularly imprinted polymers.
Biomater Sci Polym Ed. 2002; 13(6):637-49.
4) Zhiliang C, Erkang W., Xiurong Y„ Capacitive detection of glucose using molecularly imprinted polymers, Biosensors and Bioelectronics, Volume 16, Issue 3, 1 May 2001 , Pages 179-185 5) Jinqiang J. et.al. Glucose sensors based on electrodeposition of molecularly imprinted polymeric micelles: A novel strategy for MIP sensors. Biosensors and Bioelectronics, Volume 26, Issue 5, 15 January 201 1, Pages 2607-261.
The MIP of Monochrotophos for the application of chromatographic separation and isolation was reported by various workers including the following:
1 ) Zhu X1, Yang J, Su Q, Cai J, Gao Y. Molecularly imprinted polymer for monocrotophos and its binding characteristics for organophosphorous pesticides. Ann Chim. 2005 Nov-Dec;95(l l-12):877-84.
2) Zhu X', Yang J, Su Q, Cai J, Gao Y. Selective solid-phase extraction using molecularly imprinted polymer for the analysis of polar organophosphorus pesticides in water and soil samples.J Chromatogr A. 2005 Oct 28; 1092(2): 161-9.
All applications of MIPs Icnown so far relate to chemical analysis and/or diagnostics.
In analytical separation science, molecularly imprinted polymers have been applied in several analytical techniques, such as liquid chromatography, capillary electrochromatography and capillary electrophoresis, solid phase extraction, immunoassay, and as a selective sorbent in chemical sensors.
Use of MIPs as selective sorbents in capillary electrochromatography is another application in analytical chemistry. [ Lars I. Andersson. Molecular imprinting: developments and applications in the analytical chemistry field. J of Chromato B, 745 (2000) 3-13] The use of MIPS as stationary phases for HPLC is further example in anlyticla chemistry.
Incorporation of chromophoric reporter molecules into molecular imprinting sensor designs has been researched to a considerable extent. [ Al-Kindy S, Badia R, Sua rez-Rodriguez JL, Diaz-Garcia ME. 2000. Molecularly imprinted polymers and optical sensing applications. Crit. Rev. Anal. Chem. 30:291-309.]
A variety of methods have been employed to attain optical transduction of specific binding events by using MIPs via fluorimetry.
Molecular-imprint based solid-phase extraction (MISPE) is currently the most advanced application area in which MIPs are used. The majority of studies into MISPE have used cartridges or columns off-line from the downstream analytical separation.
MIPs have been used for selective solid-phase extraction for the analysis of polar organophosphorus pesticides (monocrotophos, mevinphos, phosphamidon, omethoate) in water and soil samples. The MIPs enabled the selective extraction of four organophosphorus pesticides successfully from water and soil samples, demonstrating the potential of molecularly imprinted solid-phase extraction for rapid, selective, and cost- effective sample pretreatment (Zhu X et al 2005).
The concept of selective uptake of an analyte of interest and subsequent generation of a characteristic electrochemical signal is being probed by many for sensor development. Based on this technique Piletsky and co-workers, demonstrating how changes in the electroconductivity (or electroresistance) of an imprinted membrane can be attributed to rebinding phenomena. [Sergeyeva TA, Piletsky SA, Brovko AA, Slinchenko EA, Sergeeva LM, Elskaya AV. 1999. Selective recognition of atrazine by molecularly imprinted polymer membranes. Development of conductometric sensor for herbicides detection. Anal. Chim. Acta 392: 105-1 1 1.
Piletsky SA, Parhometz YP, Lavryk NV, Panasyuk TL,Elskaya AV. 1994. Sensors for low-weight organicmolecules based on molecular imprinting technique. Sens. Actuators B 19: 629-631. Piletskii SA, Kurys YI, Rachkov AE, Elskaya AV. 1994. Formation of matrix polymers sensitive to aniline and phenol. Russ. J. Electrochem. 30: 990-992.]
Objects of the invention
There are a large number of ingredients of food eaten by people which are generally undesirable to the living body of all because they are toxic or are undesirable for certain people on account of their medical/clinical condition. Undesirable materials in food comprise any material/s which is/are harmful or toxic to a living body of its consumer. Despite extensive information generated on the use of MIPs in analytical chemistry and diagnostics, although several undesirable materials intrude into our digestive tract due to pollution or for other reasons, no one has so far contemplated use of MIPs and developing methods to use MIPs for detoxifying, totally or partly, the contents of digestive tract before such undersirable materials before they are absorbed in the digestive tract. An objective of this invention is to invent methods of using MIPs for removal in the digestive tract of undersirable substances consumed through food. Such a use has not been disclosed so far nor has it been suggested by any one or by any document so far.
Patients suffering from diseases e.g. Diabetes mellitus (Type - 2 Diabetes), for example, are prohibited from intake of glucose / sugars beyond a certain amount per meal, wherein intake of glucose / sugars in an amount excess to that limitation per meal are undesirable materials to that patient. Similarly, inappropriate use of pesticides on fruits and vegetables has lead to increased intake of pesticides which are harmful to living body. Also, fatty acids like palmitic acid are undesirable materials for patients suffering from moderate to high cholesterol problems. Hence to overcome all these, the present invention provides composition for oral administration comprising specific MIP(s) for reducing the amount of undesirable material consumed orally through food being absorbed in the living body through digestive tract.
The primary object of the present invention is to provide molecular traps or molecularly imprinted polymers (MIPs) for reducing the amount of undesirable materials consumed orally (through food) from getting absorbed in the digestive tract by a living body by oral administration of MIPs.
Another object of the present invention is to provide a novel composition of said MIPs having selective trapping capability of undesirable materials in the digestive tract of a living body. Another object of the present invention is to provide novel process for preparation of the novel composition of said MIPs having selective trapping capability of undesirable materials in the digestive tract of a living body.
Another object of the present invention is to provide process for preparation of MIPs used for treatment of various diseases, poisoning or medical complications caused because oi absorption of undesirable materials in the digestive tract.
Still another objective of present invention was to provide MIPs specific for palmitic acid, a process to produce them. Further, the objective also was to provide compositions containing MIPs specific for palmitic acid for oral consumption so as to reduce the absorption in the digestive tract of palmitic acid from context of the digestive tract.
Summary of the invention
This invention comprises a process/method of using oral administration of a composition of Molecularly imprinted polymers (MIPs) imprinted with one or more of undesirable material/s for reducing the amount of one or more of the undesirable material/s being absorbed from the digestive tract of a living body. It is an embodiment of this invention that the Molecularly Imprinted Polymers in the compositions have capability of trapping specific undesirable material/s from food in the digestive tract of a living body. In an embodiment of the process/method of this invention, the oral administration of the composition of MIP is done, either by consuming (a) a food in which MIP/s is/are incorporated/involved in the food, or (b) a tablet containing the MIP and the food, or (c) a sachet of MIP containing composition and the food, or (d) a fluid to which a composition of MIP/s is added and the food. The composition of MIP/s comprises (a) single molecularly imprinted polymer or a combination of molecularly imprinted polymers, and (b) optionally is combined with excipients; and is one of the embodiments of the instant invention. The excipients comprise one or more selected from the group of a binder, diluents, disintigrant, glidant and lubricant.
The composition of the Molecularly Imprinted Polymer may have one or more molecularly imprinted polymers in the range of between 200 - 700mg, binder/s in the range of 2 - 5%, diluents/s in the range of 5 - 20%, disintegrant/s in the range of 2 - 3%, glidant/s in the range of 1 - 2% and lubricant/s in the range of 1 - 5%
The invention is also embodied in a processes for the preparation of specific molecularly imprinted polymer as claimed in claim 1, comprising steps of: (a) dissolving a template specific for an undesirable material in a solvent, wherein the undesirable material is a material that is needed to be totally or partly prevented from absorption in the digestive tract, (b) adding a monomer and crosslinker, (c) bubbling nitrogen gas, (d) heating the mixture, (e) dissolving the initiator in minimum quantity of solvent, (f) carrying out the polymerization at an elevated temperature for a time wherein the temperature and time is selected to facilitate completion of polymerization and obtaining polymer complex, (g) filtering the polymer complexes, washing with solvent, drying, grinding the dried polymer complex and sieving, (h) releasing of template from polymer complex by suspending the polymer complex in solvent under constant stirring at speed, temperature and time effective for achieving release of the template from the polymer, (i) After the template release from polymer complex, polymer complex was again kept in pH 5 - 7 buffer under stirring for a period of time enough to get complete removal of template to get Molecularly Imprinted Polymer specific for the template, (j) filtering and drying the Molecularly Imprinted Polymer (MIP) at moderately elevated temperature for a period of time enough for drying, (j) reducing the dried MIP to a fine particulate material of uniform particle size and sieved to give a powder of fixed upper particle size.
In one embodiment of this invention, the specific template molecule is selected one or more from the group consisting of glucose, pesticides, palmitic acid or other fatty acids, monocrctophos or any other molecule needed to be prevented or reduced from being absorbed in the digestive tract,
The process/method of this invention comprising using/use of oral administration of a composition of Molecularly imprinted polymers (MIPs) specific for trapping one or more undesirable materials comprises a means to reduce the risk of or for preventing various diseases, poisoning or medical complications caused because of respective undesirable materials.
In one embodiment, this invention comprises a molecularly imprinted polymer having specific capability of binding/trapping palmitic acid. This invention also comprises a process for the preparation of palmitic acid specific molecularly imprinted polymer comprising following steps: (a) accurately weighing palmitic acid as template, (b) dissolving palmitic acid in chloroform in a container/reactor equipped with a stirrer, a reflux condenser and a nitrogen inlet, (c) adding monomer 2- hydroxy ethyl methacrylate (HEMA) and crosslinker ethylene glycoldimethacrylate (EGDMA) and bubbling nitrogen gas for removal of atmospheric oxygen until a homogeneous mixture is formed, (d) heating the mixture to an elevated temperature, dissolving by adding azobisisobutyronitrile (AIBN) dissolved in minimum quantity of chloroform, and carrying out polymerization by maintaining the temperature at the elevated temperature, for a period of time to complete the polymerization, (d) filtering the polymer complex formed, washing with chloroform and drying the same, (e) grinding the dry polymer complex and sizing by passing through a sieve, (f) releasing the palmitic acid from the polymer complex by stirring in chloroform, and (g) keeping the polymer complex after release of palmitic acid was again in chloroform for a period of time enough for complete removal of palmitic acid.
A molecularly imprinted polymer of claim 13 having specificity to trap palmitic acid in a polymer matrix derived from polymerization of monomer 2- hydroxy ethyl methacrylate (HEMA) with a crosslinker ethylene glycoldimethacrylate (EGDMA).
This invention is also embodied in a composition of Molecularly imprinted Polymer comprising a molecularly imprinted polymer and excipients, The excipients may comprise, one or more selected from the group of binder, diluents, disintigrents, glidants and lubricants. The composition of the Molecularly imprinted Polymer may be a tablet or a powder. The powder may be filled in sachets. In yet another embodiment this invention comprises a process/method of reducing the amount of one or more of undesirable material/s being absorbed from the digestive tract of a living body comprising a step of oral administration of a composition of Molecularly imprinted polymers (MIPs) imprinted with the undesirable material/s.
Detailed description of the invention The present invention provides specific MIPs which are used for reducing the amount of specific undesirable materials consumed orally (through food) from getting absorbed from the digestive tract of a living body. Absoiption in the digestive tract of living body of undesirable materials such as glucose (for patients suffering from Diabetes mellitus (Type- 2 Diabetes)); harmful pesticides (present in fruits and vegetables and which causes toxicity); fatty acids like palmitic acid (for patients suffering from moderate to high cholesterol problems); etc., can be reduced getting absorbed from digestive tract of a living body by use of the MIPs specific for the respective/relevant undesirable material. Further, the present invention provides processes for the manufacture of undesirable material specific MIPs which are used for reducing the amount of undesirable materials absorbed from digestive tract of a living body. Also, according to the present invention, composition for oral administration comprising specific MIPs is disclosed which are used for reducing the amount of specific undesirable materials being absorbed from digestive tract of a living body.
In the present invention molecular traps or molecularly imprinted polymers (MIPs) are prepared for reducing the amount of undesirable materials absorbed from a living body by oral administration of MIPs. The process for preparation of the same is described hereunder. For oral administration novel composition is prepared by a novel processes for the preparation of the same using said MIPs having selective trapping capability of undesirable materials from a living body. In a further embodiment, this invention also comprises use of MIPs for treatment or prevention or reducing the risk of various diseases, poisoning or medical complications caused because of various undesirable materials. MIP, a polymer that has been processed/prepared using the molecular imprinting technique, which leaves cavities in polymer matrix with affinity to a chosen "template" molecule, wherein the process generally involves polymerization of monomers in the presence of a chosen template molecule which is extracted afterwards and leaves complementary cavities behind which can be upto micro or nano cavities. Now prepared polymers can be used in applications like chemical separations, catalysis, or molecular sensors. The present invention discloses MIPs and composition using MIPs. The processes for the preparation of specific MIPs require specific template molecule, functional monomer(s), crosslinking agent(s), an initiator and solvents.
The template molecule should be chemically inert under the polymerization condition. It is observed that, in general, small, multi-functional, template molecules give rise to highly specific imprints whilst larger, mono-functional template molecules produce imprinted sites which have less specificity. According to the present invention, the specific unwanted material the absorption of which is required to be reduced from the digestive tract is selected as specific template for making MIP specific for the same.
According to the present invention, specific template molecules are specific undesirable materials such as, including but not limited to, glucose, pesticides, fatty acids like palmitic acid, etc for which specific MIPs are prepared. Template molecule is of central importance as it directs the organization of the functional groups dependent to the functional monomers.
According to the present invention, monomers used for preparation of polymers can be selected from the group including but not limited to methacrylic acid, acrylic acid and hydroxyethylmethacrylate, 4 Vinyl pyridine, 2 vinyl pyridine, allyl amine, Acrylamide, methacrylamide, acrylonitrile, methyl methacrylate, styrene, ethylstyrene, 2- (trifluromethyl)-acrylic acid etc Polymers undergo regiospecific, weak, complementary, interaction with a particular moiety of the template molecule. Also, the polymers contain a polymerizable unit.
The interaction between the functional monomer and template during polymerization are complementary to those between polymer and template in the rebinding step. Due to complimentary of the binding site between the polymer and template, a host -guest relationship is produced due to non-covalent and covalent bonding (where a host is the polymer complex and the guest is the template in this case) According to the present invention, crosslinking agents are used to fix the guest-binding sites firmly in the desired structure of MIPs. Crosslinking agents make the MIPs insoluble in solvents and facilitate their practical applications as disclosed in the present invention. Different kinds of crosslinking agents can be used to control both the structure of the guest-binding sites and the chemical environments around them for efficient imprinting process.
By choosing an appropriate crosslinking agent, random copolymerization occurs successfully, and the functional residues (derived from the functional monomers) are uniformly distributed in the polymer network. Crosslinking agent used in the preparation of MIPs based on polymer can be selected from the group including but not limited to ethylene glycol dimetacrylate (EGDMA) divinyl benzene, l ,3,diisopropenyl benzene, tetra methylenedimethacrylate, trimethyl propane trimethacrylate, pentaerythritotriacrylate, pentaerythritoltetracrylate, NN-methylene bismethacrylamide, NN-ethylene bismethacrylamide, and the like. Further, selection of monomers (which undergo polymerization to produce polymers) and crosslinking agents are be based on their structure specificity with template molecules; e.g. the monomer and crosslinking agents used for the following template molecules are as follows but not limited to: a. Glucose: Methacrylic acid (monomer), acrylic acid 4 Vinyl pyridine, 2 vinyl pyridine, allyl amine, and EGDMA (crosslinking agent), l,3,diisopropenyl benzene,tetramethylenedimethacrylate,trimethylpropanetrimethacrylate ...2- hydroxy ethyl methacrylate, divinyl benzene; b. Monocrotophos: - Acrylic acid (monomer), methacrylic acid, 2-hydroxy ethyl methacrylate 4 Vinyl pyridine, 2 vinyl pyridine, and EGDMA (crosslinking agent) ;,Divinylbenzene, l,3,diisopropenylbenzene, tetra methylenedimethacrylate, 2-hydroxy ethyl methacrylate;
Initiators are used as the radical source in free radical polymerization. Polymerization initiate through liberation of nescent oxygen. It should be soluble in solvent. The initiator can be selected from the group but not limited to azobisisobutriyonitrile, benzyl peroxide, azobisdimethylvaleronitrile, dimethylacetalof benzene.
The solvents can be selected but not limited to water, chloroform, methanol,, ethanol, Butanol, Isopropyl alcohol, benzene, tolune, xylene, dimethylsulpoxide, and the like.
The influence of polymerization solvent has multiple roles: it solubilizes all the monomer in the pre-polymerization mixture before polymerization, it stabilizes the template monomer pre-polymerization complex, it acts as a porogen helping to control the porosity of resulting polymer.
Following methods for the preparation of the specific MIPs can be used to make MIPs of this invention: a) Self-assembly method, which involves the formation of polymer by combining all elements of the MIP and allowing the molecular interactions to form the cross- linked polymer with the template molecule bound. b) The second method of formation of MIPs involves covalently linking the imprint molecule to the monomer. After polymerization, the monomer is cleaved from the template molecule.
MIPs prepared according to the above processes are generally opaque, vitreous and brittle in nature. MIPs should be reduced to a fine particulate material of uniform particle size. Typically, this is achieved by grinding processes or by mechanical means. MIPs are then sieved to give a powder of fixed upper particle size (25-45 μπι).
Thus prepared MIPs are non-toxic and useful for removal of residual toxin, toxic material from food in the digestive tract to prevent or reduce the risk of medical disorders and many diseases.
In a further embodiment, this invention is embodied in a novel composition of specific MIPs for oral administration which are used for reducing the amount of specific undesirable materials being absorbed from the digestive tract in a living body. Said composition of MIPs comprises of either specific MIPs only or the said composition comprises specific MIPs and at least one another pharmaceutically acceptable excipient. The said pharmaceutically acceptable excipient may include but not restricted to binders, diluents, disintegrants, glidants, lubricants, etc. The said compositions of specific MIPs can be dispensed as such in powder form which can be sprinkled over or incoiporated in foods, dispensed in sachets, consumed directly with fluid (e.g. water), filled in capsules, or dispensed / compressed as tablets.
Binders can be selected from the group including but not limited to, Starch paste and PVP- 30.
Diluents can be selected from the group including but not limited to, Starch, lactose , Microcrystalline cellulose and Dibasic calcium Phosphate.
Disintegrants can be selected from the group including but not limited to, Sodium starch glycolate, Sodium lauryl sulphate, cross carmalose sodium, cross-providone, dry starch.
Glidants can be selected but not limited to, Talc and magnesium stearate.
Lubricants can be selected from the group including but not limited to talc, magnesium
t
stearate, Aerosil.
The composition may comprise single MIP or combination of MIPs.
In the present invention the comparison study was also made between MIPs and Non-MIPs and their compositions. The study found beneficial for oral administration.
Illustrative experiments on MIPs specific for glucose demonstrated effective glucose binding in In Vitro experiments as well as In vivo experiments when fed to diabetic rats. Statistical analysis of variance shows that the mean blood sugar level of the second group (Diabetic control Rat + glucose) which was diabetic rat control was higher in first an< second hour after feeding the rats than the mean blood sugar level of the fourth grouj (Diabetic control rat + glucose+MIP) which was MIP fed group. These differences, a: analysed by statistical methods of analysis of variance, were significant at P=0.01. Thus efficacy of MIPs of glucose in preventing rise in blood glucose level in first two hours wa: evident. A person skilled in the art would readily understand that this binding is dos< dependent and from case to case, requirements for quantity of binding can be determinec and consumption of quantity of the glucose-specific MIP for can be determined to bind anc remove from the digestive tract desired quantity of glucose to achieve targeted control or blood glucose.
In In Vitro experiments, selectivity of glucose-specific MIP over fructose is alsc demonstrated when added to a solution containing glucose as well as fructose.
In Vitro and InVivo experiments conducted on palmitic acid in the same way confirmed efficacy of palmitic acid-specific MIPs in binding palmitic acid and its removal from the digestive tract resulting in healthier lipid profile of rats consuming palmitic acid-specific MIPs. Statistical analysis of variance shows that the mean level of triglycerises, as well a LDL cholesterol was higher and HDL cholesterol lower in the second group (Vehicle + HFD) (which was group of hyperlipidemia induced rats, than the respective values in the fourth group (HFD+MIP (225 mg/kg) (which is hyperlipidelima induced group fed with MIPs specific for palmitic acid). These differences, as analysed by statistical methods of analysis of variance, were significant at P=0.01. Thus, efficacy of MIPs specific for palmitic acid in removal of the same from digesting tract before absorption was evident. A person skilled in the art would readily understand that this binding is dose dependent and from case to case, requirements for quantity of binding can be determined and consumption of quantity of the palmitic acid specific MIP for can be determined to bind and remove from the digestive tract desired quantity of palmitic acid to achieve targeted control on lipid profile.
Selectivity of palmitic acid specific MIP was also illustrated in In Vitro experiments.
Illustrative In Vitro experiments on monocrotophos, an insecticide which is a potential contaminant in vegetables and similar food products, have also shown specific absorption by monocrotophos-specific MIPs. Selectivity of monocrotophos-specifc MIP has also been verified in In Vitro experiments. Although In Vivo experiments have not been conducted on this, going by the results on glucose and palmitic acid, a person skilled in the art would readily understand that selective removal of not only monocrotophos but of any small molecular weight substance that is consumed with food and needs removal before it is absorbed in digestive tract is possible and no separate verification is needed in each case. By proper selection of polymers and MIPs, it may also be possible to selectively remove in the digestive tract the bacteria, viruses and cells from consumed food.
It is noteworthy that polymers are ideally suited for such a detoxification since being high molecular weight materials, they will not be absorbed by body and removed as they are through faeces. It is pointed out here that the compositions of MIPs used here contain "excipients". For the purpose of this specification, "excipients" shall be understood as substances that makes the composition suitable for and meant for oral consumption as a means for capturing undersirable substances in the digestive tract and preventing or reducing their absorption in the living body through the digestive tract. It is also understood that the "excipients" are the substances that make the MIPs associated with them a composition that is not meant for analytical, diagnostic or sensory purposes.
"excipients" point out to ingredients which are edible and the resulting composition shall be a pharmaceutical composition or a composition that can be consumed with food, hence entirely different than the compositions of MIPs which are meant for analytical, diagnostic or sensory purposes. The present invention is illustrated but is not limited in any way by following examples, and modifications thereto falling within the scope and spirit of the appended claims and which would be obvious to a person skilled in the art based upon the disclosure herein, are also considered to be included within the scope of this invention.
Examples All animal experiment described below were approved by Institutional Animal Ethics committee (IAEC) of Pinnacle Biomedical Research Institute (PBRI) Bhopal (CPCSEA Reg. No. 1283/C/09/CPCSEA).
Example 1.1:
Preparation of MIP Ingredients were taken in the quantities given below in Table 1 : Table 1: Ingredients taken for preparation of MIPs
Figure imgf000025_0001
Synthesis of polymer complex by solvent polymerization technique
Accurately weighed quantity of a template of an undersirable material orally consumed through food was dissolved in a solvent. Monomer and crosslinker were added and nitrogen gas was bubbled for 20 - 40 min.
- The mixture was heated to 40 - 70°C and initiator is dissolved in minimum quantity of solvent.
Polymerization was carried out by maintaining the temperature at 40 - 70°C for 7 - 12 hours.
Obtained polymer complexes were filtered, washed with solvent and dried which was subsequently ground and sieved.
Release of the template from polymer complex was carried out wherein the polymer complex was suspended in solvent under constant stirring (30 - 60 rpm) at temperature 30 - 45°C. After the template release from polymer complex, the polymer complex was again kept in pH 5 - 7 buffer for 20 - 26 h under stirring for complete removal of the template.
- The MIP made free from the template was again filtered and dried at 40 - 65°C for 2 - 6 hours.
MIPs prepared according to the above processes are generally produced are opaque, vitreous and brittle in nature. MIPs should be reduced to a fine particulate material of uniform particle size. Typically, this is achieved by grinding processes or by mechanical means. MIPs are then sieved to give a powder of fixed upper particle size (25-45 μπι). Using the above MIP a novel composition is prepared for oral administration.
Novel composition of moiecularly imprinted polymer comprises molecularly imprinted polymer between 200 - 700mg, binder 2 - 5%, diluents 5 - 20%, disintigrent 2 - 3%, glidant 1 - 2%, lubricant I - 5%
Example 1.2: Process for preparation of Palmitic acid specific MIP: Accurately weighed quantity of palmitic acid as template was dissolved in chloroform in a four necked round bottom 250 mL capacity flask equipped with a stirrer, a reflux condenser and a nitrogen inlet. To this, monomer 2- hydroxy ethyl methacrylate (HEMA) and crosslinker ethylene glycoldimethacrylate (EGDMA) were added and nitrogen gas was bubbled for 30 min. The mixture was heated to 60°C and azobisisobutyronitrile (AEBN) dissolved in minimum quantity of chloroform was added and polymerization was carried out by maintaining the temperature at 60"C for further 12 h. Polymer was filtered, washed with chloroform and dried. This was subsequently grounded in a mortar-pestle and passes through #16 and retained on retained on 40.
The palmitic acid release was carried out in 100 mL volumetric flask (stoppered) using polymer complex 1 g in 100 mL of chloroform. The volumetric flask assembled on a magnetic stirrer for constant stirring (50 rpm). Aliquots of 1 mL was withdrawn at specific time intervals (1 h) and analyzed by UV-Vis spectrophotometer for palmitic acid content at 440 nm.
After the palmitic acid release from polymer complex, polymer complex was again kept in chloroform for 24 h under stirring for complete removal of palmitic acid. From this solution, 0.1 mL of sample was withdrawn and analyzed by UV-Vis spectrophotometer. This process was continue up to the two consecutive reading giving the same absorbance in UV-Vis spectrophotometer which means that the drug was completely removed from polymer and MIP was formed which was again filtered and dried at 60°C for 4 h.
Example 2: Process for preparation of a formulation/composition containing MIPs
Required quantity of MIP was taken and mixed with diluents. The slurry of binder was prepared and incorporated in above mixture to prepare a dough ready for wet passing. This dough was passed through granulating sieve. The prepared granules were dried. The required quantity of glidant and lubricant was added and the granules were ready for compression.
Thus prepared granules/MIP powder can be sprinkled over or involved/incorporated in foods, dispensed in sachets, consumed directly with fluid (e.g. water), filled in capsules, or dispensed / compressed as tablets as per the required dose. Ihe dosages are used for in-vitro and in-vivo studies. In in-vitro study the MIP(s) are compared with NIP. The results showed that while MIPs were capable of binding with respective undesired materials or capturing them, NIPs were not able to appreciably bind with or capture the undesirable materials. Thereafter the MIP(s) formulations were studied in-vivo.
Synthesis of Non Imprinted Polymer (NIP)
A non imprinted polymer was prepared exactly the same way as the MIP, but in the absence of the template.
Glucose In -vitro Results Absorption of glucose by molecularly imprinted polymer (MIP) :
MIP of glucose (1 g) was added in the beaker containing glucose (1 g) dissolved in 50 mL of pH 6.8 buffer and was kept for 8 h under stirring. From this solution, 0.1 mL of sample was withdrawn at specified time intervals and analyzed by UV-Vis spectrophotometer for balance quantity of glucose remained in solution and calculated for glucose uptake by MIP. Further, above MIP was filtered and washed with 10 mL of pH 6.8 buffer to determine the removal of glucose adhering on the surface of MIP by UV- Vis spectrophotometer and actual quantity of glucose absorbed by MIP was calculated. Table 2: Cumulative percentage of glucose absorbed* by five batches MIPs for glucose labelled as G1-G5. NIP - Non-Imprinted Polymer
Figure imgf000029_0001
A) In- vivo antidiabetic activity a) Selection of animals
Healthy Sprague Dawley rats (200±50 g) were selected for in-vivo study. b) Experimental induction of diabetes Rats were grouped in the following manner for the said protocol (six animals per group). Animals were made diabetic with intra-peritoneal injection of 65 mg/kg dose of freshly prepared streptozocin in citrate buffer. Animals with blood glucose level more than 200 mg/dL were considered as diabetic and continued further for the study. Overnight fasted animals were challenged with 3 g/kg oral dose of glucose. Half hour prior to glucose administration MIP of glucose was administered orally 250 mg/kg.
Diabetic rats were further assigned randomly to following groups (each group contains six animals). Group I - Normal rats received vehicle solution normal saline and glucose 3 g/kg of body weight
Group II - Diabetic control rats treated with glucose 3 g/kg of body weight
Group III - Diabetic control rats treated with glucose 3 g/kg of body weight and glibenclamide 10 mg/kg of body weight
Group rv - Diabetic rats treated with glucose 3 g/kg of body weight and MIP of glucose 250 mg/kg of body weight
Powdered MIPs specific for glucose were administered orally to the experimental groups of rats. c) Results:
After oral glucose administration blood sample was collected at 1 , 2, 3, 4 and 5 h from tail vein and blood glucose level was estimated for glucose tolerance test.
Table 3: Effect of glucose specific MIPs on blood glucose level through in- vivo study.
Figure imgf000030_0001
Diabetic control rat
238.83±7. 125.33±2. 81.33±6. 76.50±6. 75.83± 75.33±4. + Glucose +
68 a 80 a 80 a 12 a 5.42 a 84 a Glibenclamide
Diabetic control rat 237.33±18 291.50±2 250.83±2 237.67± 232.17 233.00± + Glucose + MIP .36 5.99 a 0.25 a 10.27 ±7.99 4.24
* All data presented in Mean ± SD (N=6)
a P<0.001 as compared to Diabetic control rats + Glucose treated group
The data showed that in the group I (normal rat) treated with normal saline and 3 g/kg glucose at 0 h the blood glucose level was 77.17 mg/dL. After 1, 2 and 5 h the blood glucose level was 126, 87.83 and 76.33 mg/dL respectively. 1
In the group II (Diabetic control rat) treated with 3 g/kg glucose at 0 h the blood glucose level was 231.50 mg/dL. After 1 , 2 and 5 h the blood glucose level was 334.67, 285.30 and 229.17 mg/dL respectively.
While in group III (Diabetic control rat) treated with drug (glibenclamide 10 mg/kg) and 3 g/kg glucose at 0 h the blood glucose level was 238.83 mg/dL. After 1 , 2 and 5 h the blood glucose level was 125.33, 81.33 and 75.33 mg/dL respectively.
In the group IV (Diabetic control rat) treated with MIP of glucose 250 mg/kg and glucose 3 g/kg at 0 h the blood glucose level was 237.33 mg/dL. After 1 , 2 and 5 h the blood glucose level was 291.50, 250.83 and 233.00 mg/dL respectively. Statistical analysis of variance shows that the mean blood sugar level of the second group (Diabetic control Rat + glucose) which was diabetic rat control was higher in first and second hour after feeding the rats than the mean blood sugar level of the fourth group (Diabetic control rat + glucose+MIP) which was MIP fed group. These differences, as analysed by statistical methods of analysis of variance, were significant at P=0.01. d) Stability studies
The stability studies were conducted for MIP of glucose as per ICH guidelines.
The result showed that MIP of glucose are stable at accelerated condition upon the condition of 40°C / 75% RH. e) Selectivity of the glucose-imprinted polymer
Cross-reactivity of the MIP was evaluated against analogous molecules, two different monosaccharide's glucose and fructose were selected to test the selective binding characteristic of MIP.
Table 4: Comparison and selectivity of the MIPs specific for glucose template
Figure imgf000033_0001
* PC, fiie meas xem&Hls were pttfomsed n tr plicaSes
Palmitic acid In -vitro Results
Absorption of palmitic acid by molecularly imprinted polymer (MIP) :
MIP of palmitic acid (1 g) was added in the volumetric flask containing palmitic acid (1 g) dissolved in 100 mL of chloroform and was kept for 8 h under stirring. From this solution, 0.1 mL of sample was withdrawn at specified time interval and analyzed by UV-Vis spectrophotometer for balance quantity of palmitic acid remained in solution and calculated for palmitic acid uptake by MIP. Further, above MIP was filtered and washed with 10 mL of chloroform to determine the removal of palmitic acid adhere on the surface of MIP by UV- Vis spectrophotometer and actual quantity of palmitic acid absorbed by MIP was calculated. Table 5: Cumulative percentage of palmitic acid absorbed* by six batches MIPs for palmitic acid labelled as P1-P6. NIP - Non-Imprinted Polymer
Figure imgf000034_0001
B) In- vivo antih perlipidemic activity
a) Selection of animals
Healthy Wistar rats (200±30 g) were selected for in-vivo study.
b) Composition of high fat diet and experimental induction of hyperlipidemia
High fat diet cocktail was prepared by mixing cholesterol, cholic acid in 1 liter of coconut oil. The animals were fed a high-cholesterol diet for 10 days. To confirm the induction of hyperlipidemia, blood samples were collected by retro orbital puncture. The total cholesterol (TC) concentration of the blood samples was then determined using a standard diagnostic kit (span diagnostic) by Biochemical autoanalyser (Star 21). The rats were then divided into 4 groups of 6 animals based on their cholesterol levels, after which the treatments were administered orally twice a daily for 10 days. Hyperlipidemic rats were further assigned randomly to following groups (each group contains six animals).
Group I - Normal rats received vehicle solution normal saline
Group II - Rats treated with high fat diet for 10 days
Group III - Rats treated with high fat diet for 10 days and simvastatin 10 mg/kg of body weight.
Group IV - Rats treated with high fat diet for 10 days and specific MIPs of palmitic acid 225 mg/kg twice a daily for 10 days Powdered MIPs specific for palmitic acid were administered orally to the experimental group of rats - Group IV. c) Results
Lipidemic profile of the rats were evaluated after 10 days wherein the four groups of rats showed following results:
In below table vehicle treated group results is demonstrate the value of lipid profile in normal animals (ie. Untreated animals). Whereas vehicle +HFD (High Fat Diet) demonstrate value of lipid profile in hyperlipidemic animals without any treatment. These two groups are base line results. Table 6: Experimental protocol and its effect on lipidemic profile
TC- Total cholesterol, TG- Triglyceride
Figure imgf000036_0001
* All data presented in Mean ± SD (N=6)
a P<0.001 as compared to Vehicle + HFD treated group
The data showed that in the group I (normal rat) treated with normal saline at 10th day the total cholesterol (TC), triglyceride (TG), LDL and HDL level was 73.18 mg/dL, 69.98 mg/dL, 32.71 mg/dL and 37.71 mg/dL respectively.
In the group II (High fat diet control) at 10th day TC, TG, LDL and HDL level was 174.03 mg/dL, 153.98 mg/dL, 85.93 mg/dL and 17.38 mg/dL respectively. In the group III (HFD control) treated with Simvastatin 10 mg/kg at 10th day TC, TG, LDL and HDL level was 104.85 mg/dL, 89.08 mg/dL, 41.15 mg/dL and 31.81 mg/dL respectively.
In the group IV (High fat diet control) treated with MIP of glucose 225 mg/kg twice a daily at 10th day the TC, TG, LDL and HDL level was 130.2 mg/dL, 1 12.81 mg/dL, 56.76 mg/dL and 25.71 mg/dL respectively.
Statistical analysis of variance shows that the mean level of triglycerises, as well a LDL cholesterol was higher and HDL cholesterol lower in the second group (Vehicle + HFD) (which was group of hyperlipidemia induced rats, than the respective values in the fourth group (HFD+MIP (225 mg/kg) (which is hyperlipidelima inuced group fed with MIPs specific for palmitic acid). These differences, as analysed by statistical methods of analysis of variance, were significant at P=0.01. d) Stability study
The stability studies were conducted for MIP of palmitic acid as per ICH guidelines. The result showed that MIP of palmitic acid are stable at accelerated condition upon the condition of 40°C / 75% RH. e) Selectivity of the palmitic acid-imprinted polymer
Comparison between saturated fatty acids from (peanut oil and safflower oil) absorbed by palmitic acid-imprinted polymer and Peanut oil has approximately 1 1 % palmitic acid and safflower oil has approximately 4.5% palmitic acid. Table 7: Concentration of saturated fatty acids content in peanut oil and safflower oil
Figure imgf000038_0001
Table 8: Selectivity of MIP - Cumulative percentage of palmitic acid absorbed by MIP
Figure imgf000038_0002
The palmitic acid from pea nut oil absorbed by MIP was 7.99% in 2h and 10.30% in 8h, while palmitic acid from safflower oil absorbed by MIP was 3.39% in 2h and 4.40% in 8h.
C) In-vitro study of absorption of monochrotophos
Monocrotophos In -vitro Results
Absorption of monocrotophos acid by molecularly imprinted polymer (MIP) MIP of monocrotophos (1 g) was added in the volumetric flask containing monocrotophos (1 g) dissolved in 100 mL of water and was kept for 8 h under stirring. From this solution, 0.1 mL of sample was withdrawn at specified time interval and analyzed by UV-Vis spectrophotometer for balance quantity of monocrotophos remained in solution and calculated for monocrotophos uptake by MIP. Further, above MIP was filtered and washed with 10 mL of water to determine the removal of monocrotophos adhere on the surface of MIP by UV- Vis spectrophotometer and actual quantity of monocrotophos absorbed by MIP was calculated.
Table 9: Cumulative percentage of monocrotophos absorbed by six batches MIPs for monocrotophos labelled as M1-M6. NIP - Non-Imprinted Polymer
Figure imgf000039_0001
a) Stability and absorption studies
The stability studies were conducted for MIP of monocrotophos as per ICH guidelines.
The result showed that MIP of monocrotophos was stable at accelerated condition upon the condition of 40°C / 75% RH. b) Selectivity of the monocrotophos-imprinted polymer
Cross-reactivity of the MIP was evaluated against analogous molecules, two different organophosphorus pesticides monocrotophos and mevinphos were selected to test the selective binding characteristic of MIP.
MIP of ( 1 g) suspended in 50 mL containing monocrtophos ( 1 g) and monocrotophos (0.5 g) plus mevinphos (0.5 g) solution was kept for 8 h under stirring. From this solution, 0.1 mL of sample was withdrawn at specified time interval and analyzed by UV-Vis spectrophotometer for balance quantity of monocrotophos remained in solution and calculated for monocrotophos uptake by MIP.
Selectivity of monocrotophos imprinted polymer was studied; the MIP showed the 29.30% monocrotophos absorbed. These results indicate that MIP only have affinity for monocrotophos. Analogues of a template cannot bind with all activity sites created by the template in the cavity, so the retention is not obvious.
Table 10: Selectivity of the monocrotophos imprinted polymer
Figure imgf000040_0001
The monocrotophos absorbed by MIP from monocrotophos solution was 26.62% in 2 h and 29.30%) in 8 h and in case of mixture absorption of monocrotophos was 53.14% in 2 h and 58.56%) in 8 h respectively.

Claims

1. A process/method of using oral administration of a composition of Molecularly imprinted polymers (MIPs) imprinted with one or more of undesirable material/s for reducing the amount of one or more of the undesirable material/s being absorbed from the digestive tract of a living body.
2. The process/method of claim 1 wherein the Molecularly Imprinted Polymers in the compositions have capability of trapping specific undesirable material/s from food in the digestive tract of a living body.
3. The process of claim 1 wherein the oral administration of the composition of MIP is done, either by consuming (a) a food in which MIP/s is/are incorporated/involved in the food, or (b) a tablet containing the MIP and the food, or (c) a sachet of MIP containing composition and the food, or (d) a fluid to which a composition of MIP/s is added and the food.
4. The process of claim 1 wherein the composition of MIP/s comprises (a) single molecularly imprinted polymer or a combination of molecularly imprinted polymers, and (b) optionally is combined with excipients.
5. The process of claim 1 wherein the composition of the Molecularly Imprinted Polymer comprises one or more of molecularly imprinted polymers and one and more of, binder/s, diluents, disintigrent/s, glidant/s and lubricant s.
6. The composition of the Molecularly Imprinted Polymer of claim 5 wherein: the one or more molecularly imprinted polymers range between 200 - 700mg, binder/s range between 2 - 5%, diluent/s range between 5 - 20%, disintigrent/s range between 2 - 3%, glidant/s range between 1 - 2% and lubricant/s range between 1 - 5%.
7. The composition of Molecularly Imprinted Polymer of claim 6, wherein
a. the binders are selected from a group consisting of one or more of a starch paste and PVP-30,
b. the diluents are selected from a group consisting of one or more of starch, lactose, micro crystalline cellulose, Dibasic Calcium Phosphate, disintegrants can be sodium starch glycolate, sodium lauryl sulphate, cross carmalose sodium, cross-providone and dry starch,
c. glidants are selected from a group consisting of one or more of talc and magnesium stearate, and
d. lubricants are selected from a group consisting of one or more of talc, magnesium stearate and aerosol.
8. A composition of the Molecularly Imprinted Polymer of claim 7 wherein the composition is either a tablet or a powder.
9. A process for the preparation of specific molecularly imprinted polymer as claimed in claim 1 , comprising steps of:
a. dissolving a template specific for an undesirable material in a solvent, wherein the undesirable material is a material that is needed to be totally or partly prevented from absorption in the digestive tract,
b. adding a monomer and crosslinker,
c. bubbling nitrogen gas, d. heating the mixture,
e. dissolving the initiator in minimum quantity of solvent,
f. carrying out the polymerization at an elevated temperature for a time wherein the temperature and time is selected to facilitate completion of polymerization and obtaining polymer complex,
g. filtering the polymer complexes, washing with solvent, drying, grinding the dried polymer complex and sieving,
h. releasing of template from polymer complex by suspending the polymer complex in solvent under constant stirring at speed, temperature and time effective for achieving release of the template from the polymer, i. After the template release from polymer complex, polymer complex was again kept in pH 5 - 7 buffer under stirring for a period of time enough to get complete removal of template to get Molecularly Imprinted Polymer specific for the template.
j. filtering and drying the Molecularly Imprinted Polymer (MIP) at moderately elevated temperature for a period of time enough for drying, k. reducing the dried MIP to a fine particulate material of uniform particle size and sieved to give a powder of fixed upper particle size.
10. The processes for the preparation of specific molecularly imprinted polymer of claim 9, wherein:
a. the specific template molecule is selected one or more from the group consisting of glucose, pesticides, palmitic acid or other fatty acids, monocrotophos or any other molecule needed to be prevented or reduced from being absorbed in the digestive tract,
b. monomer is selected one or more from the group consisting of methacrylic acid, acrylic acid and hydroxyethylmethacrylate,
c. crosslinking agent one or more from the group consisting of ethylene glycol dimetacrylate (EGDMA) divinyl benzene, l,3,diisopropenyl benzene, tetra methylenedimethacrylate, trimethyl propane trimethacrylate, pentaerythritotriacrylate, pentaerythritoltetracrylate, NN-methylene bismethacrylamide and N -ethylene bismethacryl amide,
d. initiator is selected one or more from the group consisting of azobisisobutriyonitrile, benzyl peroxide, azobisdimethylvaleronitrile and dimethylacetalof benzene,
e. solvent is selected one or more from the group consisting of water, chloroform, methanol and dimethylsulpoxide.
f. the nitrogen is bubbled for 20-40 min,
g. heating of the mixture with initiator is done at 40-70 °C,
h. temperature maintained for polymerization is 40 - 70°C and for 7 - 12hours, i. stirring of the polymer complex suspended of water for release of template from polymer complex is done at 30 - 60 rpm and at temperature 30 - 45°C,
j. the period of time for which stirring is done in buffer for complete removal of template is for 20 - 26 h, k. drying of the MIP was done at 40 - 65°C for 2 - 6 hours,
1. the fixed upper particle size of the powder of MIP is 25-45 μηι.
1 1. The process/method of using oral administration of a composition of Molecularly imprinted polymers (MIPs) specific for trapping one or more undesirable materials to reduce the risk of or for preventing various diseases, poisoning or medical complications caused because of respective undesirable materials.
12. The processes claim 9 for the preparation of Palmitic acid specific molecularly imprinted polymer comprising following steps:
a. Accurately weighing palmitic acid as template,
b. dissolving palmitic acid in chloroform in a container/reactor equipped with a stirrer, a reflux condenser and a nitrogen inlet.
c. adding monomer 2- hydroxy ethyl methacrylate (HEMA) and crosslinker ethylene glycoldimethacrylate (EGDMA) and bubbling nitrogen gas until a homogeneous mixture is formed,
d. heating the mixture to an elevated temperature, dissolving by adding azobisisobutyronitrile (AIBN) dissolved in minimum quantity of chloroform, and carrying out polymerization by maintaining the temperature at the elevated temperature, for a period of time to complete the polymerization,.
e. filtering the polymer complex formed, washing with chloroform and drying the same,
f. grinding the dry polymer complex and sizing by passing through a sieve, g. releasing the palmitic acid from the polymer complex by stirring in chloroform, h. keeping the polymer complex after release of palmitic acid was again in chloroform for a period of time enough for complete removal of palmitic acid.
13. The processes claim 1 1 for the preparation of palmitic acid specific molecularly imprinted polymer, wherein: a. the nitrogen gas was bubbled in step (c) of claim 1 1 for 30 min, b. the temperature of mixture of step (c) of claim 1 1 was maintained at 60"C for a period of 12 h, c. the dry powdered MIP was sized by retaining fraction that passed through a sieve #16 and retained on 40, d. the period of time, for which after release of palmitic acid the polymer complex is kept again in chloroform under stirring for complete removal of palmitic acid in step (g) of claim 1 1 , is for 24 h.
14. A molecularly imprinted polymer having specific capability of binding/trapping palmitic acid.
15. A molecularly imprinted polymer of claim 13 having specificity to trap palmitic acid in a polymer matrix derived from polymerization of monomer 2- hydroxy ethyl methacrylate (HEMA) with a crosslinker ethylene glycoldimethacrylate (EGDMA).
16. A process/method of reducing the amount of one or more of undesirable material/s being absorbed from the digestive tract of a living body comprising a step of oral administration of a composition of Molecularly imprinted polymers (MIPs) imprinted with the undesirable material/s.
PCT/IN2014/000288 2013-04-30 2014-04-30 Molecular traps for certain undesirable materials WO2014178081A2 (en)

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