WO2008010172A2 - Chitins and chitosans in an activated form and their slimming, hypoglycaemic, hypolipidaemic properties - Google Patents
Chitins and chitosans in an activated form and their slimming, hypoglycaemic, hypolipidaemic properties Download PDFInfo
- Publication number
- WO2008010172A2 WO2008010172A2 PCT/IB2007/052803 IB2007052803W WO2008010172A2 WO 2008010172 A2 WO2008010172 A2 WO 2008010172A2 IB 2007052803 W IB2007052803 W IB 2007052803W WO 2008010172 A2 WO2008010172 A2 WO 2008010172A2
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- polymers
- chitosans
- crosslinked
- activated
- solution
- Prior art date
Links
- 229920001661 Chitosan Polymers 0.000 title claims abstract description 87
- 229920002101 Chitin Polymers 0.000 title claims abstract description 32
- 230000000055 hyoplipidemic effect Effects 0.000 title description 2
- 230000002218 hypoglycaemic effect Effects 0.000 title 1
- 229920000642 polymer Polymers 0.000 claims abstract description 84
- 239000000725 suspension Substances 0.000 claims abstract description 28
- 238000000034 method Methods 0.000 claims abstract description 24
- 235000005911 diet Nutrition 0.000 claims abstract description 21
- 230000008569 process Effects 0.000 claims abstract description 20
- 238000002360 preparation method Methods 0.000 claims abstract description 17
- 230000037213 diet Effects 0.000 claims abstract description 16
- 238000011282 treatment Methods 0.000 claims abstract description 13
- 235000016709 nutrition Nutrition 0.000 claims abstract description 11
- MSWZFWKMSRAUBD-UHFFFAOYSA-N beta-D-galactosamine Natural products NC1C(O)OC(CO)C(O)C1O MSWZFWKMSRAUBD-UHFFFAOYSA-N 0.000 claims abstract description 9
- MSWZFWKMSRAUBD-QZABAPFNSA-N beta-D-glucosamine Chemical compound N[C@H]1[C@H](O)O[C@H](CO)[C@@H](O)[C@@H]1O MSWZFWKMSRAUBD-QZABAPFNSA-N 0.000 claims abstract description 9
- 239000013589 supplement Substances 0.000 claims abstract description 9
- 201000001421 hyperglycemia Diseases 0.000 claims abstract description 5
- 208000031226 Hyperlipidaemia Diseases 0.000 claims abstract description 4
- 238000010438 heat treatment Methods 0.000 claims abstract description 4
- 208000008589 Obesity Diseases 0.000 claims abstract 2
- 230000003213 activating effect Effects 0.000 claims abstract 2
- 206010012601 diabetes mellitus Diseases 0.000 claims abstract 2
- 235000020824 obesity Nutrition 0.000 claims abstract 2
- 239000000243 solution Substances 0.000 claims description 25
- 238000004132 cross linking Methods 0.000 claims description 24
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 claims description 15
- 239000007788 liquid Substances 0.000 claims description 14
- 239000000047 product Substances 0.000 claims description 13
- 230000004913 activation Effects 0.000 claims description 12
- 239000003431 cross linking reagent Substances 0.000 claims description 11
- 238000005406 washing Methods 0.000 claims description 10
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 10
- -1 aliphatic aldehyde Chemical class 0.000 claims description 9
- SXRSQZLOMIGNAQ-UHFFFAOYSA-N Glutaraldehyde Chemical compound O=CCCCC=O SXRSQZLOMIGNAQ-UHFFFAOYSA-N 0.000 claims description 8
- 150000001299 aldehydes Chemical class 0.000 claims description 7
- XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 claims description 6
- 239000012670 alkaline solution Substances 0.000 claims description 5
- 239000012062 aqueous buffer Substances 0.000 claims description 5
- 230000006196 deacetylation Effects 0.000 claims description 5
- 238000003381 deacetylation reaction Methods 0.000 claims description 5
- 239000002245 particle Substances 0.000 claims description 5
- 125000000008 (C1-C10) alkyl group Chemical group 0.000 claims description 3
- 229910052784 alkaline earth metal Inorganic materials 0.000 claims description 3
- 150000001342 alkaline earth metals Chemical class 0.000 claims description 3
- 229910052751 metal Inorganic materials 0.000 claims description 3
- 239000002184 metal Substances 0.000 claims description 3
- 238000001994 activation Methods 0.000 abstract description 11
- 239000003925 fat Substances 0.000 description 16
- 235000000346 sugar Nutrition 0.000 description 16
- 238000009835 boiling Methods 0.000 description 15
- 230000000694 effects Effects 0.000 description 15
- 150000008163 sugars Chemical class 0.000 description 13
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 12
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 12
- 229930006000 Sucrose Natural products 0.000 description 11
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 11
- 235000013681 dietary sucrose Nutrition 0.000 description 11
- 229960004793 sucrose Drugs 0.000 description 11
- 239000003921 oil Substances 0.000 description 9
- 235000019198 oils Nutrition 0.000 description 9
- 238000012360 testing method Methods 0.000 description 9
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 8
- 241001465754 Metazoa Species 0.000 description 8
- 239000007853 buffer solution Substances 0.000 description 7
- 238000000605 extraction Methods 0.000 description 7
- 235000013305 food Nutrition 0.000 description 7
- 239000004006 olive oil Substances 0.000 description 7
- 235000008390 olive oil Nutrition 0.000 description 7
- 230000035484 reaction time Effects 0.000 description 7
- 238000003756 stirring Methods 0.000 description 7
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
- 238000006243 chemical reaction Methods 0.000 description 6
- 239000007864 aqueous solution Substances 0.000 description 5
- 230000037396 body weight Effects 0.000 description 5
- 230000000378 dietary effect Effects 0.000 description 5
- 235000012054 meals Nutrition 0.000 description 5
- 241000700159 Rattus Species 0.000 description 4
- 238000010521 absorption reaction Methods 0.000 description 4
- HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 description 4
- 229920005615 natural polymer Polymers 0.000 description 4
- 239000000843 powder Substances 0.000 description 4
- 238000001179 sorption measurement Methods 0.000 description 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- 239000004471 Glycine Substances 0.000 description 3
- 208000035150 Hypercholesterolemia Diseases 0.000 description 3
- 102000007330 LDL Lipoproteins Human genes 0.000 description 3
- 108010007622 LDL Lipoproteins Proteins 0.000 description 3
- 229920001222 biopolymer Polymers 0.000 description 3
- 239000008280 blood Substances 0.000 description 3
- 210000004369 blood Anatomy 0.000 description 3
- 239000012295 chemical reaction liquid Substances 0.000 description 3
- 239000000470 constituent Substances 0.000 description 3
- 230000000875 corresponding effect Effects 0.000 description 3
- 235000013367 dietary fats Nutrition 0.000 description 3
- BNIILDVGGAEEIG-UHFFFAOYSA-L disodium hydrogen phosphate Chemical compound [Na+].[Na+].OP([O-])([O-])=O BNIILDVGGAEEIG-UHFFFAOYSA-L 0.000 description 3
- 229910000397 disodium phosphate Inorganic materials 0.000 description 3
- 235000019800 disodium phosphate Nutrition 0.000 description 3
- 239000012153 distilled water Substances 0.000 description 3
- 238000011156 evaluation Methods 0.000 description 3
- 230000006870 function Effects 0.000 description 3
- 239000004615 ingredient Substances 0.000 description 3
- 235000020845 low-calorie diet Nutrition 0.000 description 3
- 235000019799 monosodium phosphate Nutrition 0.000 description 3
- 239000008055 phosphate buffer solution Substances 0.000 description 3
- 239000013049 sediment Substances 0.000 description 3
- AJPJDKMHJJGVTQ-UHFFFAOYSA-M sodium dihydrogen phosphate Chemical compound [Na+].OP(O)([O-])=O AJPJDKMHJJGVTQ-UHFFFAOYSA-M 0.000 description 3
- 229910000162 sodium phosphate Inorganic materials 0.000 description 3
- 239000006228 supernatant Substances 0.000 description 3
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- 239000002253 acid Substances 0.000 description 2
- 150000001412 amines Chemical group 0.000 description 2
- 238000004458 analytical method Methods 0.000 description 2
- 230000008901 benefit Effects 0.000 description 2
- 239000002775 capsule Substances 0.000 description 2
- 238000004587 chromatography analysis Methods 0.000 description 2
- 150000001875 compounds Chemical class 0.000 description 2
- 235000020940 control diet Nutrition 0.000 description 2
- 238000001816 cooling Methods 0.000 description 2
- 230000002596 correlated effect Effects 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 229960002442 glucosamine Drugs 0.000 description 2
- 239000008103 glucose Substances 0.000 description 2
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 2
- 238000000338 in vitro Methods 0.000 description 2
- 230000000968 intestinal effect Effects 0.000 description 2
- 229950006780 n-acetylglucosamine Drugs 0.000 description 2
- 239000003960 organic solvent Substances 0.000 description 2
- 230000009467 reduction Effects 0.000 description 2
- 150000003839 salts Chemical class 0.000 description 2
- 239000011780 sodium chloride Substances 0.000 description 2
- 238000012546 transfer Methods 0.000 description 2
- 238000005303 weighing Methods 0.000 description 2
- IORISFYTXJVNFE-UHFFFAOYSA-N 2,3-dinitrobenzenesulfonic acid Chemical compound OS(=O)(=O)C1=CC=CC([N+]([O-])=O)=C1[N+]([O-])=O IORISFYTXJVNFE-UHFFFAOYSA-N 0.000 description 1
- MSWZFWKMSRAUBD-IVMDWMLBSA-N 2-amino-2-deoxy-D-glucopyranose Chemical compound N[C@H]1C(O)O[C@H](CO)[C@@H](O)[C@@H]1O MSWZFWKMSRAUBD-IVMDWMLBSA-N 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical compound OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 description 1
- 239000004215 Carbon black (E152) Substances 0.000 description 1
- 229920001268 Cholestyramine Polymers 0.000 description 1
- VYZAMTAEIAYCRO-UHFFFAOYSA-N Chromium Chemical compound [Cr] VYZAMTAEIAYCRO-UHFFFAOYSA-N 0.000 description 1
- 206010014476 Elevated cholesterol Diseases 0.000 description 1
- 241000593508 Garcinia Species 0.000 description 1
- 235000000885 Garcinia xanthochymus Nutrition 0.000 description 1
- 241000282414 Homo sapiens Species 0.000 description 1
- ZMJBYMUCKBYSCP-UHFFFAOYSA-N Hydroxycitric acid Chemical compound OC(=O)C(O)C(O)(C(O)=O)CC(O)=O ZMJBYMUCKBYSCP-UHFFFAOYSA-N 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 1
- 239000004472 Lysine Substances 0.000 description 1
- OVRNDRQMDRJTHS-UHFFFAOYSA-N N-acelyl-D-glucosamine Natural products CC(=O)NC1C(O)OC(CO)C(O)C1O OVRNDRQMDRJTHS-UHFFFAOYSA-N 0.000 description 1
- OVRNDRQMDRJTHS-FMDGEEDCSA-N N-acetyl-beta-D-glucosamine Chemical compound CC(=O)N[C@H]1[C@H](O)O[C@H](CO)[C@@H](O)[C@@H]1O OVRNDRQMDRJTHS-FMDGEEDCSA-N 0.000 description 1
- 241000700157 Rattus norvegicus Species 0.000 description 1
- 230000021736 acetylation Effects 0.000 description 1
- 238000006640 acetylation reaction Methods 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 239000003463 adsorbent Substances 0.000 description 1
- 125000003172 aldehyde group Chemical group 0.000 description 1
- 229910001860 alkaline earth metal hydroxide Inorganic materials 0.000 description 1
- 230000004075 alteration Effects 0.000 description 1
- 235000001014 amino acid Nutrition 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 235000015895 biscuits Nutrition 0.000 description 1
- 235000008429 bread Nutrition 0.000 description 1
- 150000001720 carbohydrates Chemical class 0.000 description 1
- 235000014633 carbohydrates Nutrition 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 235000019219 chocolate Nutrition 0.000 description 1
- 235000012000 cholesterol Nutrition 0.000 description 1
- 229910052804 chromium Inorganic materials 0.000 description 1
- 239000011651 chromium Substances 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- 208000029078 coronary artery disease Diseases 0.000 description 1
- 229920006037 cross link polymer Polymers 0.000 description 1
- 230000007423 decrease Effects 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 230000029087 digestion Effects 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 230000004064 dysfunction Effects 0.000 description 1
- 238000010828 elution Methods 0.000 description 1
- 239000000686 essence Substances 0.000 description 1
- 230000002550 fecal effect Effects 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 235000013312 flour Nutrition 0.000 description 1
- 235000003599 food sweetener Nutrition 0.000 description 1
- 235000015203 fruit juice Nutrition 0.000 description 1
- 235000013376 functional food Nutrition 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 208000019622 heart disease Diseases 0.000 description 1
- 235000009200 high fat diet Nutrition 0.000 description 1
- 229920001519 homopolymer Polymers 0.000 description 1
- 229930195733 hydrocarbon Natural products 0.000 description 1
- 150000002430 hydrocarbons Chemical class 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 230000014759 maintenance of location Effects 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 150000002739 metals Chemical class 0.000 description 1
- 230000000877 morphologic effect Effects 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 235000021590 normal diet Nutrition 0.000 description 1
- 235000019313 oat gum Nutrition 0.000 description 1
- 239000001912 oat gum Substances 0.000 description 1
- 239000008194 pharmaceutical composition Substances 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 235000002378 plant sterols Nutrition 0.000 description 1
- GNSKLFRGEWLPPA-UHFFFAOYSA-M potassium dihydrogen phosphate Chemical compound [K+].OP(O)([O-])=O GNSKLFRGEWLPPA-UHFFFAOYSA-M 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 230000002441 reversible effect Effects 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 235000019980 sodium acid phosphate Nutrition 0.000 description 1
- UIIMBOGNXHQVGW-UHFFFAOYSA-M sodium bicarbonate Substances [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 239000008347 soybean phospholipid Substances 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- 238000010998 test method Methods 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 238000011269 treatment regimen Methods 0.000 description 1
- 230000003442 weekly effect Effects 0.000 description 1
- 239000013585 weight reducing agent Substances 0.000 description 1
- 235000013618 yogurt Nutrition 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08L—COMPOSITIONS OF MACROMOLECULAR COMPOUNDS
- C08L5/00—Compositions of polysaccharides or of their derivatives not provided for in groups C08L1/00 or C08L3/00
- C08L5/08—Chitin; Chondroitin sulfate; Hyaluronic acid; Derivatives thereof
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
- A23L29/00—Foods or foodstuffs containing additives; Preparation or treatment thereof
- A23L29/20—Foods or foodstuffs containing additives; Preparation or treatment thereof containing gelling or thickening agents
- A23L29/275—Foods or foodstuffs containing additives; Preparation or treatment thereof containing gelling or thickening agents of animal origin, e.g. chitin
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
- A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
- A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
- A23L33/17—Amino acids, peptides or proteins
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08B—POLYSACCHARIDES; DERIVATIVES THEREOF
- C08B37/00—Preparation of polysaccharides not provided for in groups C08B1/00 - C08B35/00; Derivatives thereof
- C08B37/0006—Homoglycans, i.e. polysaccharides having a main chain consisting of one single sugar, e.g. colominic acid
- C08B37/0024—Homoglycans, i.e. polysaccharides having a main chain consisting of one single sugar, e.g. colominic acid beta-D-Glucans; (beta-1,3)-D-Glucans, e.g. paramylon, coriolan, sclerotan, pachyman, callose, scleroglucan, schizophyllan, laminaran, lentinan or curdlan; (beta-1,6)-D-Glucans, e.g. pustulan; (beta-1,4)-D-Glucans; (beta-1,3)(beta-1,4)-D-Glucans, e.g. lichenan; Derivatives thereof
- C08B37/0027—2-Acetamido-2-deoxy-beta-glucans; Derivatives thereof
- C08B37/003—Chitin, i.e. 2-acetamido-2-deoxy-(beta-1,4)-D-glucan or N-acetyl-beta-1,4-D-glucosamine; Chitosan, i.e. deacetylated product of chitin or (beta-1,4)-D-glucosamine; Derivatives thereof
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
- A23V2002/00—Food compositions, function of food ingredients or processes for food or foodstuffs
Definitions
- This invention relates to D-glucosamine polymers and the corresponding acetylated glucosamine homopolymers, namely N-acetyl-D-glucosamine; it relates in particular to chitosans, optionally in crosslinked form, and chitins, both in activated form. It also relates to the process for producing chitosans and chitins in activated form, and to nutritional preparations that include one or both of said compounds as a basic element, and the use of said nutritional preparations to reduce and control the cholesterol and sugar levels, mainly in the blood.
- LDLs low-density lipoproteins
- Chitin and chitosan biopolymers have an action mechanism which is attributable to their ability to trap (adsorb) fats and sugars from food, thus preventing their enteric absorption.
- the chitins and chitosans in the preparations currently on the market require a daily dose, for the treatment of excess body weight or hyperlipidaemia, of up to six grams a day for a minimum period ranging between 30 and 60 days.
- said polymers would therefore need to be capable of adsorbing a larger amount of fats and sugars.
- chitosans and chitins are poly( ⁇ -1 ,4-glucosamine) and poly( ⁇ -1 ,4-N-acetylglucosamine) respectively.
- the. weight-average molecular weight of said biopolymers is generally between 80,000 and 2,000,000, or even higher.
- chitins and chitosans the latter optionally in crosslinked form, when pretreated with boiling strong bases for a few minutes, considerably increase their ability to sequester dietary fats and sugars per unit of weight of chitin or chitosan polymer.
- said treatment produces "activated" chitins and chitosans which are capable of: a. trapping dietary fats weighing around two/three times as much as the activated polymer, namely approx. four/five times as much as the natural polymer; unlike the natural polymer, the adsorbed fats are not released, even by extraction with organic solvents such as acetone; b.
- a first advantage obtained with the use of activated chitins and chitosans, optionally crosslinked, is therefore the administration of considerably lower doses of said active constituents, while achieving the same effect.
- This invention therefore relates to D-glucosamine polymers in activated form, said polymers being chosen from among chitins, chitosans and crosslinked chitosans, and the activation being obtained with a process that involves treating the polymers with a strong base and subsequent heating of the polymers.
- Said D-glucosamine polymers used in this invention in both crosslinked and non-crosslinked form, have an apparent density that ranges between approximately 0.3 and 0.80 g/ml, and preferably between 0.5 and 0.7 g/ml.
- the particle size of these polymers typically ranges between 80 and 400 mesh, and preferably between 80 and 200 mesh.
- the chitosans have a degree of deacetylation which typically ranges between 89 and 95%, but those with a degree of deacetylation exceeding 90% are preferred.
- the strong base is preferably a hydroxide of an alkaline or alkaline earth metal, and the hydroxide is more preferably selected from among NaOH and KOH.
- the preferred hydroxide is NaOH.
- Said hydroxide is preferably used in the form of a solution, typically an aqueous solution; the solution of said alkaline or alkaline earth metal hydroxide ranges between approximately 0.5 and 3 N, and more preferably between 1.5 and 2.5 N.
- the suspension is cooled to ambient temperature.
- the suspension is preferably cooled rapidly; said cooling time is approximately between 30 m and 6 h, and preferably between 30 m and 90 m, for a batch of between 5,000 and 10,000 kg.
- the product of reaction thus obtained is separated from the reaction liquid and rinsed with a washing liquid until the washing liquid has a pH of between 6 and 9, and preferably between 7 and 9.
- the washing liquid is preferably selected from water and an aqueous buffer solution, such as a buffer solution at an acid pH formed by acetic acid and sodium or potassium acid phosphate.
- the product of reaction is dried; drying is conducted, for example, in a stove at a temperature of between approximately 40 and 60 0 C until the dried product reaches a constant weight. [0025] If the activation conditions are extended beyond the soda time and concentration parameters indicated, a decline in adsorbent properties will be observed, probably correlated with an alteration in the polymer structure.
- activated crosslinked chitosans present a considerable increase in their ability to sequester dietary fats and sugars per unit of weight of polymer compared with activated but not crosslinked chitosans.
- the aliphatic aldehyde is preferably a hydrocarbon with a C1-C10 alkyl chain.
- the aldehyde is preferably chosen from among the monoaldehydes and dialdehydes.
- the preferred example of monoaldehyde is formaldehyde.
- the particularly preferred example of dialdehydes is glutaraldehyde ((OHC-(CH2)3-CHO)).
- the crosslinked chitosans according to the invention have a degree of crosslinking which ranges between approximately 1:50 and 1:130, and in particular between 1:60 and 1:120.
- the chitosans can be also be crosslinked on either activated or non- activated polymers.
- the chitosan crosslinking process involves reacting the chitosans with a cross-linking agent chosen from among the group of aliphatic aldehydes, preferably with a C1-C10 alkyl chain.
- the aldehyde is preferably chosen from among the monoaldehydes and dialdehydes.
- the preferred example of monoaldehyde is formaldehyde.
- the particularly preferred example of dialdehydes is glutaraldehyde (OHC-(CH2)3-CHO).
- Said buffer solution is obtained by adding acid salts of alkaline metals to the water, preferably a pair of sodium acid phosphates, namely Na2HPO4 and NaH2PO4, or the sodium carbonate/bicarbonate pair.
- Said buffer solution has a salt molarity of between approximately 0.01 and 0.5, and preferably between 0.05 and 0.1.
- the quantity of aliphatic aldehyde reacted with the polymer to be crosslinked is chosen on the basis of the degree of crosslinking to be obtained and the number of functional aldehyde groups in the molecule.
- the ratio between chitosan and cross-linking agent, expressed as moles of glucose contained in the polymer compared with the moles of cross- linking agent, typically ranges between 1 :1 -10-1 and 1 :1 -10-3.
- the cross-linking agent can be added, for example, in the form of an aqueous solution.
- the molarity of the cross-linking agent namely the aldehyde, can range, for example, between 0.1 and 10, and preferably between 0.5 and 2.
- Said organic amine compound is preferably an aminoacid, such as glycine or lysine. Said amine compound is added greatly in excess of the aldehyde functions which have not yet reacted; it is generally a solution which has approximately the same molarity as the solution containing the aldehyde.
- the suspension is preferably stirred at stages (2) and (3).
- lonisation of the hydroxyl functions is believed to give the preactivated polymers the ability to adsorb large amounts of fats and sugars, with a strong, physical bond that is not reversible, even by extraction with organic solvents and/or adequate buffer solutions.
- Said polymers in activated form, optionally crosslinked, are dispensed as diet supplements, preferably in the form of powder, capsules, sachets or tablets.
- the dose of said diet supplements is between approximately 0.5 and 8 g/day, with a posology of approximately 1 to 4 tablets a day.
- Nutritional preparation means any edible, non-pharmaceutical composition; examples of said preparations are meal substitutes, sports foods and functional foods.
- the diet supplements and food preparations according to the invention are to be taken close to meals, preferably immediately after a meal including fatty and sugary foods. They significantly inhibit the absorption of edible fats and sugars eaten in a normal meal, thus performing a considerable slimming effect or correcting hyperlipidaemia and hyperglycaemia.
- the diet supplements and nutritional preparations according to the invention can include any other natural or artificial component known according to the state of the art and commonly used to formulate nutritional preparations, such as additives, excipients, preservatives, sweeteners, essences, colorants and optionally other active substances.
- any other natural or artificial component known according to the state of the art and commonly used to formulate nutritional preparations such as additives, excipients, preservatives, sweeteners, essences, colorants and optionally other active substances.
- the -NH2 functions still free are titrated by Habeeb's dinitrobenzene sulphonate (DNBS) method (reference A.G.S.A. Anal. Biochim., 1966, 14, 328-336).
- DNBS dinitrobenzene sulphonate
- Vl read the volume occupied by the powder on the graduated cylinder; and [0058] V. calculate the apparent density of the powder under test with the following formula:
- Non-crosslinked chitosans apparent density 0.6 g/ml, particle size 100 mesh and degree of acetylation 95%, and
- Chitosan crosslinking stage [0082] Introduce the 20 kg of chitosan activated at the preceding stage into an apparatus fitted with a stirrer, and pour onto it 200 I of an 0.07 M aqueous buffer solution of Na2HPO4/NaH2PO4 at pH 8.2, to which 2 I of a 1 M aqueous solution of formaldehyde is added. [0083] Heat the suspension thus obtained to 37°C for 18 hours, stirring occasionally. Stop the reaction by adding excess glycine (1 I) and filter the suspension through a B ⁇ ckner filter to separate the activated, crosslinked chitosan from the reaction liquid.
- Tables 1 and 2 show the types of polymers used and the data obtained relating to the grams of olive oil adsorbed using the polymers activated under said different conditions described in examples A and B according to the invention.
- D% represents the percentage difference between the fats trapped by the activated chitosan or chitin and the control chitosan or chitin.
- Table 3 shows the types of polymers used and the data obtained using the activated polymers under different conditions according to this invention, said data being compared with those obtained using untreated polymers.
- the item “D%” indicates the percentage of oil removed by extraction.
- Table 4 shows the types of polymers used and the data obtained using polymers activated under different conditions according to the invention.
- D% represents the percentage difference between the saccharose trapped by the activated chitosan or chitin and by the control chitosan or chitin.
- the non-activated chitosan and chitin adsorb 0.9 g and 0.7 g of saccharose respectively.
- the data show that the polymers according to the invention adsorb more saccharose than the non-activated control polymers.
- Example 5 Place 5 g of activated, crosslinked chitosan produced in example D in a pre- calibrated low-pressure chromatography column (diameter and length of column 1 cm and 25 cm respectively); the chitosan constitutes the chromatography bed.
- Table 7 shows the treatment regimen.
Abstract
A process for activating D-glucosamine polymers chosen from among chitins, chitosans and crosslinked chitosans and the activated D-glucosamine polymers obtained from the said process. The activation process comprises the following stages: a) treating the polymers with an 0.5 to 3 N solution of a strong base, and b) heating the suspension to a temperature of between 80 and 110°C and maintaining said temperature for between 2 and 10 minutes. A diet supplement including a nutritional preparation including the said activated polymers. The said diet supplements and nutritional preparations are to be used for the treatment of obesity, hyperlipidaemia, hyperglycaemia and diabetes.
Description
Title
CHITINS AND CHITOSANS IN AN ACTIVATED FORM AND THEIR SLIMMING
HYPOGLICAEMIC, HYPOLIPIDAEMIC PROPERTIES
Description
[0001] This invention relates to D-glucosamine polymers and the corresponding acetylated glucosamine homopolymers, namely N-acetyl-D-glucosamine; it relates in particular to chitosans, optionally in crosslinked form, and chitins, both in activated form. It also relates to the process for producing chitosans and chitins in activated form, and to nutritional preparations that include one or both of said compounds as a basic element, and the use of said nutritional preparations to reduce and control the cholesterol and sugar levels, mainly in the blood.
[0002] It is well known that some natural ingredients reduce the plasma cholesterol level following a reduction in the levels of low-density lipoproteins (LDLs). There is known to be a close connection between elevated cholesterol levels associated with LDLs and an increased risk of heart and coronary disease.
[0003] These known natural ingredients include soya lecithin, plant sterols and D- glucosamine polymers. Products containing said natural ingredients are therefore already well known. In particular, preparations including chitins, chitosans and derivatives thereof are now in established use in the health sector as dietary/slimming agents due to their safety for human beings.
[0004] Chitin and chitosan biopolymers have an action mechanism which is attributable to their ability to trap (adsorb) fats and sugars from food, thus preventing their enteric absorption.
[0005] A number of studies in the literature demonstrate the effect of these biopolymers in reducing the absorption of fats and sugars without causing any toxic effects (Jennings CD. et al., "A comparison of the lipid- lowering and intestinal morphologic effects of cholestyramine, chitosan and oat gum in rats" in Proc. Soc. Biol. Med. 189 (1) : 13, 1988). In particular, the cholesterol-reducing and lipid-lowering effect is due to inhibition of fat digestion (Deuchi K. et al., "Effect of the viscosity or deacetylation degree of chitosan on fecal fat extracted from rats fed on a high-fat diet" in Biosci. Biotechnol. Bioche. (Japan) 59 (5) : 781, 1995).
[0006] As said effect performed by said structures follows precise weight ratios between the dose administered and the foods eaten, in order to obtain a
good response to the treatment it must be accompanied by a strictly controlled diet.
[0007] The chitins and chitosans in the preparations currently on the market require a daily dose, for the treatment of excess body weight or hyperlipidaemia, of up to six grams a day for a minimum period ranging between 30 and 60 days.
[0008] To obtain more marked results it would be necessary to increase the quantity of chitins and/or chitosans to exceed said daily dose, such as the dose used {inter alia) for pharmaceutical forms such as capsules or tablets. However, said increase in the dose administered is not very practical. This aspect considerably limits the dietary/slimming results obtainable with said compounds.
[0009] To overcome said limitations, preparations consisting of an association of active constituents have been proposed, such as those described in Italian patent 1284638 filed by the Applicant. It describes a diet supplement containing purified chitosans in association with organic chromium and hydroxycitrate of Garcinia cambogia. Said association produces marked cholesterol- and lipid-lowering effects, and reduces sugar absorption and body weight, after 4 weeks' treatment with just under 1 g of purified chitosans/day in association with a low-calorie diet.
[0010] In order to avoid administration of high doses of said D-glucosamine polymers or associations thereof with other active constituents, said polymers would therefore need to be capable of adsorbing a larger amount of fats and sugars.
[0011] In chemical terms, chitosans and chitins are poly(β-1 ,4-glucosamine) and poly(β-1 ,4-N-acetylglucosamine) respectively. When used for the above- mentioned purposes as dietary preparations, the. weight-average molecular weight of said biopolymers is generally between 80,000 and 2,000,000, or even higher.
[0012] It has now surprisingly been found that chitins and chitosans, the latter optionally in crosslinked form, when pretreated with boiling strong bases for a few minutes, considerably increase their ability to sequester dietary fats and sugars per unit of weight of chitin or chitosan polymer. In
particular, said treatment produces "activated" chitins and chitosans which are capable of: a. trapping dietary fats weighing around two/three times as much as the activated polymer, namely approx. four/five times as much as the natural polymer; unlike the natural polymer, the adsorbed fats are not released, even by extraction with organic solvents such as acetone; b. trapping dietary sugars weighing around five/six times as much as the activated polymer, namely approx. ten/twelve times as much as the natural polymer; unlike the natural polymer, the adsorbed sugars are not released, even after repeated rinses with buffer solution at intestinal pH.
[0013] Without wishing to tie this invention to any theory, the Applicant believes that the increase in sequestering power and the strength of the bond that fixes said polymers by virtue of said treatment is probably correlated with ionisation of the hydroxyl functions of the polymers.
[0014] A first advantage obtained with the use of activated chitins and chitosans, optionally crosslinked, is therefore the administration of considerably lower doses of said active constituents, while achieving the same effect.
[0015] Another considerable advantage of using activated chitins and chitosans is that the dietary/slimming effect of said polymers is not strictly dependent on a concomitant low-calorie diet. The patient therefore does not necessarily need to follow a low-calorie diet in order to obtain the desired effects to the desired extent.
[0016] This invention therefore relates to D-glucosamine polymers in activated form, said polymers being chosen from among chitins, chitosans and crosslinked chitosans, and the activation being obtained with a process that involves treating the polymers with a strong base and subsequent heating of the polymers.
[0017] Said D-glucosamine polymers used in this invention, in both crosslinked and non-crosslinked form, have an apparent density that ranges between approximately 0.3 and 0.80 g/ml, and preferably between 0.5 and 0.7 g/ml. The particle size of these polymers typically ranges between 80 and 400 mesh, and preferably between 80 and 200 mesh. The chitosans have a
degree of deacetylation which typically ranges between 89 and 95%, but those with a degree of deacetylation exceeding 90% are preferred.
[0018] The strong base is preferably a hydroxide of an alkaline or alkaline earth metal, and the hydroxide is more preferably selected from among NaOH and KOH. The preferred hydroxide is NaOH. Said hydroxide is preferably used in the form of a solution, typically an aqueous solution; the solution of said alkaline or alkaline earth metal hydroxide ranges between approximately 0.5 and 3 N, and more preferably between 1.5 and 2.5 N.
[0019] The polymer is treated with said alkaline solution, and the ratio between polymer and alkaline solution ranges between 1 :2.5 and 1 :5, and preferably between 1 :2.5 and 1 :3.5, the ratio being expressed in weight (g):volume (ml). The polymer forms a suspension in said alkaline solution.
[0020] The suspension is heated to approximately the boiling point of the suspension ±15°, namely between approximately 80 and 1100C, and preferably to around the boiling point of the suspension, namely the boiling point of the suspension ±5°C.
[0021] The suspension is maintained at said temperature for between approximately two and ten minutes, and preferably between four and six minutes.
[0022] At the end of this period, the suspension is cooled to ambient temperature. The suspension is preferably cooled rapidly; said cooling time is approximately between 30 m and 6 h, and preferably between 30 m and 90 m, for a batch of between 5,000 and 10,000 kg.
[0023] The product of reaction thus obtained is separated from the reaction liquid and rinsed with a washing liquid until the washing liquid has a pH of between 6 and 9, and preferably between 7 and 9. The washing liquid is preferably selected from water and an aqueous buffer solution, such as a buffer solution at an acid pH formed by acetic acid and sodium or potassium acid phosphate.
[0024] Finally, the product of reaction is dried; drying is conducted, for example, in a stove at a temperature of between approximately 40 and 600C until the dried product reaches a constant weight.
[0025] If the activation conditions are extended beyond the soda time and concentration parameters indicated, a decline in adsorbent properties will be observed, probably correlated with an alteration in the polymer structure.
[0026] It has also been surprisingly found that activated crosslinked chitosans present a considerable increase in their ability to sequester dietary fats and sugars per unit of weight of polymer compared with activated but not crosslinked chitosans.
[0027] Chitosans in crosslinked form and the corresponding crosslinking process are described in patent application MI2006A001335 filed by the Applicant. The crosslinking derives from a cross-linking agent chosen from among the group of aliphatic aldehydes.
[0028] The aliphatic aldehyde is preferably a hydrocarbon with a C1-C10 alkyl chain. The aldehyde is preferably chosen from among the monoaldehydes and dialdehydes. The preferred example of monoaldehyde is formaldehyde. The particularly preferred example of dialdehydes is glutaraldehyde ((OHC-(CH2)3-CHO)).
[0029] The crosslinked chitosans according to the invention have a degree of crosslinking which ranges between approximately 1:50 and 1:130, and in particular between 1:60 and 1:120.
[0030] Crosslinking is obtained by reaction of the chitosans with said cross-linking agent.
[0031] The chitosans can be also be crosslinked on either activated or non- activated polymers.
[0032] The chitosan crosslinking process involves reacting the chitosans with a cross-linking agent chosen from among the group of aliphatic aldehydes, preferably with a C1-C10 alkyl chain. The aldehyde is preferably chosen from among the monoaldehydes and dialdehydes. The preferred example of monoaldehyde is formaldehyde. The particularly preferred example of dialdehydes is glutaraldehyde (OHC-(CH2)3-CHO).
[0033] The crosslinking process comprises the following stages:
[0034] 1) suspend chitosan in a buffer solution having a pH ranging between 7.5 and 9.5, preferably between 8.0 and 9.0, and more preferably between 8.1 and 8.3 (suspension 1);
[0035] 2) place suspension (1) in contact with an aliphatic aldehyde as cross- linking agent and leave to react for 1 to 24 hours, preferably 1 to 18 hours, and more preferably 1 to 2 hours, at a temperature of between 15° and 40°C, and preferably between 20 and 27°C (suspension 2); and optionally:
[0036] 3) treat suspension (2) with an organic amine compound.
[0037] Said buffer solution is obtained by adding acid salts of alkaline metals to the water, preferably a pair of sodium acid phosphates, namely Na2HPO4 and NaH2PO4, or the sodium carbonate/bicarbonate pair.
[0038] Said buffer solution has a salt molarity of between approximately 0.01 and 0.5, and preferably between 0.05 and 0.1.
[0039] The quantity of aliphatic aldehyde reacted with the polymer to be crosslinked is chosen on the basis of the degree of crosslinking to be obtained and the number of functional aldehyde groups in the molecule. The ratio between chitosan and cross-linking agent, expressed as moles of glucose contained in the polymer compared with the moles of cross- linking agent, typically ranges between 1 :1 -10-1 and 1 :1 -10-3.
[0040] For example, if 100 g of chitosan (corresponding to 6.17 x 10-1 of glucose) is reacted with 6.17 x 10-2 moles of glutaraldehyde, a crosslinking ratio of 1:10 will be obtained, while a crosslinking ratio of 1 :200 is obtained by reacting 100 g of chitosan with 3.085 x 10-3 moles of glutaraldehyde.
[0041] The cross-linking agent can be added, for example, in the form of an aqueous solution. In said solution the molarity of the cross-linking agent, namely the aldehyde, can range, for example, between 0.1 and 10, and preferably between 0.5 and 2.
[0042] Said organic amine compound is preferably an aminoacid, such as glycine or lysine. Said amine compound is added greatly in excess of the aldehyde functions which have not yet reacted; it is generally a solution which has approximately the same molarity as the solution containing the aldehyde.
[0043] The suspension is preferably stirred at stages (2) and (3).
[0044] lonisation of the hydroxyl functions is believed to give the preactivated polymers the ability to adsorb large amounts of fats and sugars, with a strong, physical bond that is not reversible, even by extraction with organic solvents and/or adequate buffer solutions.
[0045] Said polymers in activated form, optionally crosslinked, are dispensed as diet supplements, preferably in the form of powder, capsules, sachets or tablets.
[0046] The dose of said diet supplements is between approximately 0.5 and 8 g/day, with a posology of approximately 1 to 4 tablets a day.
[0047] It has surprisingly been found that further optimisation of the diet/slimming results is obtained by varying the form of administration of the activated chitin and, optionally crosslinked, chitosan polymers.
[0048] It has been found that doses of the activated polymers according to the invention ranging between 2 and 20 grams a day can be administered by incorporating the activated polymers according to the invention in dry or fresh baked products, generally flour-based, such as bread, breadsticks, crackers and biscuits, and in edible liquids such as yoghurt and fruit juice; this dose is able to sequester nearly all the fats and sugars contained in a normal meal.
[0049] A further subject of this invention is therefore a nutritional preparation containing activated chitins and activated, optionally crosslinked, chitosans, obtained by the processes described above.
[0050] "Nutritional preparation" means any edible, non-pharmaceutical composition; examples of said preparations are meal substitutes, sports foods and functional foods.
[0051] The diet supplements and food preparations according to the invention are to be taken close to meals, preferably immediately after a meal including fatty and sugary foods. They significantly inhibit the absorption of edible fats and sugars eaten in a normal meal, thus performing a considerable slimming effect or correcting hyperlipidaemia and hyperglycaemia.
[0052] The diet supplements and nutritional preparations according to the invention can include any other natural or artificial component known according to the state of the art and commonly used to formulate
nutritional preparations, such as additives, excipients, preservatives, sweeteners, essences, colorants and optionally other active substances. [0053] A non-limiting example of the invention is set out below. The following test methods were used to define this invention:
- degree of crosslinking: expressed as the ratio between the number of amine functions (-NH2) that reacted with an aldehyde function of the cross-linking agent and the total number of amine functions present in the polymer.
The -NH2 functions still free are titrated by Habeeb's dinitrobenzene sulphonate (DNBS) method (reference A.G.S.A. Anal. Biochim., 1966, 14, 328-336). The number of -IMH2 functions in the titrated polymer being known, the degree of crosslinking is calculated;
- apparent density: measured using an ERWEKA SVM 202 densitometer, SERIAL NUMBER 113260.03ec, by the following method:
[0054] I. place a known quantity in weight of the powder to be tested in the graduated cylinder of the instrument;
[0055] II. set the number of strokes of the instrument to 250;
[0056] 111. start the instrument;
[0057] Vl. read the volume occupied by the powder on the graduated cylinder; and [0058] V. calculate the apparent density of the powder under test with the following formula:
APPARENT DENSITY = MASS (g) / VOLUME = (ml) [0059] Characteristics of the polymers used in the examples:
- Non-crosslinked chitosans: apparent density 0.6 g/ml, particle size 100 mesh and degree of acetylation 95%, and
- Chitins: apparent density 0.6 g/ml and particle size 100 mesh. [0060] Example A
[0061] Chitosan activation stage: Suspend 10 kg of powdered chitosan in 100 I of soda in an apparatus with a capacity of 200 I, fitted with a moving stirrer.
[0062] Heat suspension to boiling point and leave to react for a few minutes, during which stirring continues.
[0063] Cool suspension rapidly (cooling time: 30 m), decant with a decanter and filter through a Bϋckner filter.
[0064] Wash filtrate with water until the suspension liquid gives a neutral reaction.
[0065] Dry in the stove at 500C to constant weight (the moisture content of the dried product should be equal to or less than 15%).
[0066] Following said procedure, prepare 15 products consisting of activated chitosan, every time changing the reaction time at boiling point, which is ■ established at 2, 5, 10, 30 and 60 minutes; conduct three different tests for each pre-set reaction time at boiling point, only changing the normality of the added soda solution in each test. Use 0.5 N, 2.0 N and 4.0 N soda solutions.
[0067] Example B
[0068] Chitin activation stage:
[0069] Repeat example A, with the sole difference that chitosan is replaced by chitin. Vary the normality of the soda solution and the reaction time at boiling point as indicated above, to obtain 15 products based on activated chitin.
[0070] Example C
[0071] Chitosan crosslinking stage
[0072] Introduce 10 kg of chitosan into an apparatus fitted with a stirrer and pour 100 I of an 0.07 M aqueous buffer solution of Na2HPO4/NaH2PO4 at pH 8.2 onto it. Begin stirring and add 1 I of a 1 M aqueous solution of glutaraldehyde to the suspension thus obtained. Leave to react at ambient temperature for 6 hours, maintaining stirring. Stop the reaction by adding excess glycine (1 I) and filter the suspension to separate the chitosan from the reaction liquid. Transfer the filtered chitosan with a Bϋckner filter and wash with water until all trace of unreacted glutaraldehyde has been eliminated. Under said conditions, the degree of crosslinking is 1 :120.
[0073] Chitosan activation stage
[0074] The chitosan crosslinked at the preceding stage is then activated. Activation is performed by repeating the conditions and procedures described in Example A, but only using a 2 N soda solution and a reaction time from the boiling point of 5 minutes.
[0075] Example D
[0076] Repeat example C, with the sole difference that 2 I of an aqueous solution of glutaraldehyde is added instead of 0.4 I.
[0077] A crosslinked chitosan with crosslinking of 1:60 will be obtained. [0078] Example E [0079] Chitosan activation stage [0080] Repeat example A, with the sole difference that 20 kg of chitosan and 200
I of 0.5 N soda is used, and introduced into an apparatus with a capacity of
400 I.
[0081] Chitosan crosslinking stage [0082] Introduce the 20 kg of chitosan activated at the preceding stage into an apparatus fitted with a stirrer, and pour onto it 200 I of an 0.07 M aqueous buffer solution of Na2HPO4/NaH2PO4 at pH 8.2, to which 2 I of a 1 M aqueous solution of formaldehyde is added. [0083] Heat the suspension thus obtained to 37°C for 18 hours, stirring occasionally. Stop the reaction by adding excess glycine (1 I) and filter the suspension through a Bϋckner filter to separate the activated, crosslinked chitosan from the reaction liquid. Transfer the filtered chitosan and wash with water until all trace of unreacted formaldehyde has been eliminated. [0084] After washing the activated, crosslinked chitosan, dry in a stove at 50°C to constant weight (the dried product should have a moisture content equal to or less than 15%).
[0085] The degree of crosslinking of the chitosan obtained is 1 :120. [0086] Bio-pharmacological evaluation of polymer activity [0087] A) In vitro olive oil adsorption tests [0088] Example 1
[0089] Determination of fat-adsorbing power [0090] Weigh 1 g of polymer in a 50 ml centrifuge test-tube with a conical base and add 4 g of olive oil. [0091] Place test tube in a thermostat and leave polymer with oil to incubate at
37°C for two hours, stirring with a vortex 2 or 3 times for 30 seconds.
When that period has elapsed, centrifuge the suspension at 6,000 rpm for
10 minutes and eliminate the supernatant.
[0092] Establish weight of sediment and determine quantity of oil adsorbed per gram of polymer by weight analysis.
[0093] Tables 1 and 2 show the types of polymers used and the data obtained relating to the grams of olive oil adsorbed using the polymers activated under said different conditions described in examples A and B according to the invention. In the tables, D% represents the percentage difference between the fats trapped by the activated chitosan or chitin and the control chitosan or chitin.
Table 1
1) Degree of crosslinking 1 :60; 2) Degree of crosslinking 1 :120.
Table 2 - Activated chitin
[0094] The non-activated chitosan and chitin adsorb 0.6 g and 0.4 g of olive oil respectively. The data demonstrate that the polymers according to the invention adsorb more oil than the non-activated control polymers.
[0095] Example 2
[0096] Determination of strength of fat adsorption bond
[0097] Introduce 1 g of activated polymer, treated with olive oil as described in example 1 , into a 50 ml centrifuge test-tube with a conical base; add 5 ml of acetone to the same test tube and stir on vortex for 30 seconds. Then centrifuge the suspension at 6,000 rpm for 5 minutes and eliminate the supernatant.
[0098] Recover sediment and dry in the oven at 500C for 4 hours.
[0099] Weigh the dried product obtained and determine the quantity of oil which remains "trapped" after extraction with acetone by weight difference compared with the polymer not treated with oil.
[00100] Table 3 shows the types of polymers used and the data obtained using the activated polymers under different conditions according to this invention, said data being compared with those obtained using untreated polymers. The item "D%" indicates the percentage of oil removed by extraction.
Table 3
1) Activation conditions: 2 N soda solution, boiling point of 1000C and reaction time at boiling point of 5 m; 2) Degree of crosslinking: 1 :120.
[00101] The data reported in Table 3 clearly show that the larger amount of oil adsorbed on the polymer and not extracted by the polymer following said extraction treatment is the amount adsorbed on the crosslinked, activated chitosan.
[00102] B) In vitro sugar adsorption tests
[00103] Example 3
[00104] Determination of sugar-adsorbing power
[00105] Repeat example 1 , with the difference that 25 ml of a distilled water solution in which 15 g of saccharose is dissolved is introduced into each test tube instead of oil.
[00106] Table 4 shows the types of polymers used and the data obtained using polymers activated under different conditions according to the invention. In the tables, D% represents the percentage difference between the saccharose trapped by the activated chitosan or chitin and by the control chitosan or chitin.
Table 4
1) Degree of crosslinking 1:60; 2) Degree of crosslinking 1:120.
Table 5
[00107] The non-activated chitosan and chitin adsorb 0.9 g and 0.7 g of saccharose respectively. The data show that the polymers according to the invention adsorb more saccharose than the non-activated control polymers.
[00108] Example 4
[00109] Determination of strength of saccharose adsorption bond
[00110] Introduce 1 g of activated polymer, treated with olive oil as described in example 3, into a 50 ml centrifuge test-tube with a conical base. Wash polymer three times in succession, each time with 15 ml of saline phosphate buffer solution (PBS) at pH 8.0. Place test tube in a rotary vibrating mechanical stirrer and stir on vortex for 30 seconds. Then centrifuge the suspension at 6,000 rpm for 5 minutes and eliminate the supernatant.
[00111] Recover sediment and dry overnight in the oven at 500C to constant weight (the moisture level of the dried product should be equal to or lower than 15%).
[00112] Weigh the dried product obtained and determine the quantity of saccharose which remains adsorbed after extraction with buffer solution by weight difference compared with the polymer not treated with saccharose.
Table 6
1) Activation conditions: 2 N soda solution, boiling point of 1000C and reaction time at boiling point of 5 m; 2) Degree of crosslinking: 1 :120. [00113] The data reported in Table 6 clearly show that the larger amount of saccharose adsorbed on the polymer and subsequently not extracted by the polymer following said extraction treatment is the amount adsorbed on the crosslinked, activated chitosan.
[00114] C) Determination of power to adsorb both oils and sugars simultaneously [00115] Example 5 [00116] Place 5 g of activated, crosslinked chitosan produced in example D in a pre- calibrated low-pressure chromatography column (diameter and length of column 1 cm and 25 cm respectively); the chitosan constitutes the chromatography bed. [00117] The liquids listed below are conveyed in succession into the column thus prepared; the next liquid is not added until all the preceding liquid has flowed through the column: a) 5 g of olive oil, b) 50 ml of acetone which has a washing function, c) 50 ml of a 10% saccharose solution, d) 50 ml of distilled water which has a washing function, e) 20 ml of a 1 N solution of hydrochloric acid, f) 50 ml of a saline phosphate buffer solution at pH 8.0,
g) 50 ml of distilled water.
[00118] At the end, dry the column, placing it in a stove at 500C overnight, and weigh it immediately afterwards. The global quantity of fats and sugars adsorbed is determined by calculating the difference in weight of the crosslinked, activated chitosan before and after elution with said liquids. The weight found is 16.9 g.
[00119] Example 6
[00120] Repeat example 5, with the sole difference that the crosslinked, activated chitosan is replaced by activated but not crosslinked chitosan.
[00121] At the end of the experiment the activated but not crosslinked chitosan weighs 15.4 g.
[00122] The data from examples 5 and 6 demonstrate that the activated chitosans and the activated, crosslinked chitosans trap all the fats and saccharose with which they come into contact during the experiment. The fats and saccharose are not released by the activated chitosans, even after treatment with solvents or solutions at gastroenteric pH values.
[00123] Evaluation of weight-reducing activity in laboratory animals
[00124] Example 7
[00125] 50 growing female Wistar rats, with a body weight of 80 g ±5, were fed on a diet rich in fats and sugars. They were then divided into 10 groups of ten animals. Each group was treated for 30 days with a different diet from the other groups; for all groups, the diet comprised a 2.5 g chocolate which was administered before access to food.
[00126] Table 7 shows the treatment regimen.
1) Activation conditions: 2 N soda solution, boiling point of 1000C and reaction time at boiling point of 5 m; 2) Degree of crosslinking: 1:120. [00127] The weight increase trend of the rats was checked weekly. The results are set out in Table 8, wherein "D%" is the percentage difference in weight at the end of the treatment compared with the weight of the animals in the 1st group with the control diet, and "R%" is the percentage weight reduction at the end of the treatment compared with the weight of the animals in the 2nd group which received the high fat and carbohydrate diet, but without the polymers according to the invention.
Table 8
[00128] The data shown in the above table indicate that both crosslinked and activated chitosans and activated chitins are able, at the administered dose of 1 g/1 kg of the animal's weight/day, to cancel out the effects of the weight increase caused by a high-calorie diet. The effect is such that the polymers according to the invention also cause a lower weight increase than that of a rat fed on the control diet. In the case of administration of crosslinked and subsequently activated chitosans, the same effects were found at half the dose, namely 0.5 g/kg of the animal's weight/day.
[00129] Even with said body weight growth curve, the weight growth trend in the treated animals indicates that the activated (and optionally crosslinked) polymers according to the invention present good tolerability, as demonstrated by analysis of the general condition of the animals. It can therefore be deduced that said lower growth is attributable to lower assimilation of food.
[00130] D) Evaluation of slimming activity on volunteers
[00131] Example 8
[00132] Volunteers suffering from excess weight and with blood parameters indicating states of hyperglycaemia in some cases and states of hypercholesterolemia in others were treated for 60 days with activated and sometimes crosslinked chitosans like those used in example 7 above. The dosage regimen was as follows:
A) activated chitosan tablets at the dose of 3 g/day,
B) crosslinked, activated chitosan at the dose of 3 g/day,
C) the same activated chitosan as used in (A), incorporated in crackers at the dose of 3 g/day.
[00133] The dose administered was decided on the basis of the amount of excess weight and the blood dysfunction. The patients followed a normal diet throughout the treatment period. A significant reduction in excess body weight was observed, together with a tendency by the initial functional dysmetabolisms, namely hyperglycaemia and hypercholesterolaemia, to return to normal.
Claims
1. D-glucosamine polymers in activated form, said polymers being chosen from among chitins, chitosans and crosslinked chitosans, and the activation being obtained with a process that comprises the following stages: a) treating the polymers with an 0.5 to 3 N solution of a strong base, and b) heating the suspension to a temperature of between 80 and 110°C and maintaining said temperature for between 2 and 10 minutes.
2. The polymers claimed in claim 1 , wherein the strong base is a hydroxide of a metal selected from among the alkaline and alkaline earth metals.
3. The polymers claimed in claim 1 or 2, wherein the strong base solution is between 1.5 and 2.5 N.
4. The polymers claimed in claims 2 and 3, wherein the ratio between polymer and alkaline solution ranges between 1 :2.5 and 1 :5, expressed in weight (g):volume (ml).
5. The polymers claimed in claim 4, wherein the ratio ranges between 1 :2.5 and 1 :3.5.
6. The polymers claimed in claims 1 to 5, wherein the suspension is rapidly heated at the end of stage (b).
7. The polymers claimed in claims 1 to 6, wherein the washing liquid has a pH of between 6 and 9.
8. The polymers claimed in claim 7, wherein the washing liquid is selected from among water and an aqueous buffer solution.
9. The polymers claimed in claims 1 to 7, wherein the polymer is crosslinked using an aliphatic aldehyde with a C1-C10 alkyl chain as cross-linking agent.
10. The polymers claimed in claims 1 to 9, wherein the polymer is crosslinked using an aldehyde chosen from among formaldehyde and glutaraldehyde as cross-linking agent.
11. The polymers claimed in claims 9 to 10, wherein the degree of crosslinking ranges between 1 :50 and 1:130.
12. A process for activating D-glucosamine polymers chosen from among chitins, chitosans and crosslinked chitosans, the activation being obtained with a process that comprises the following stages: a) treating the polymers with an 0.5 to 3 N solution of a strong base, and b) heating the suspension to a temperature of between 80 and 1100C and maintaining said temperature for between 2 and 10 minutes.
13. The process claimed in claim 12, wherein the strong base is a hydroxide of a metal selected from among the alkaline and alkaline earth metals.
14. The process claimed in claim 12 or 13, wherein the strong base solution is between 1.5 and 2.5 N.
15. The process claimed in claims 12 to 14, wherein the ratio between polymer and alkaline solution ranges from 1 :2.5 to 1 :5, expressed in weight (g):volume (ml).
16. The process claimed in claim 15, wherein the ratio ranges between 1 :2.5 and 1 :3.5.
17. The process claimed in claims 12 to 16, wherein the suspension is rapidly heated at the end of stage (b).
18. The process claimed in claims 12 to 17, wherein the washing liquid has a pH of between 6 and 9.
19. The process claimed in claims 12 to 18, wherein the washing liquid is selected from among water and an aqueous buffer solution.
20. The process claimed in claims 12 to 19, wherein the chitins and chitosans used in stage (a), the latter in either crosslinked or non-crosslinked form, have an apparent density ranging between 0.3 and 0.80 g/ml, a particle size of between 80 and 400 mesh, and a degree of chitosan deacetylation ranging between 89 and 95%.
21. The process claimed in claim 20, wherein the apparent density ranges between 0.5 and 0.7 g/ml, the particle size ranges between 80 and 200 mesh, and the degree of chitosan deacetylation is greater than 90%.
22. A diet supplement including the polymers claimed in claims 1 to 11.
23. A nutritional preparation including the polymers claimed in claims 1 to 11.
24. The nutritional preparation claimed in claim 23, chosen from among flour- based baked products and edible liquids.
25. Use of the polymers claimed in claims 1 to 11 to prepare diet supplements and nutritional preparations for the treatment of obesity, hyperlipidaemia, hyperglycaemia and diabetes.
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
EP07805146A EP2046838A2 (en) | 2006-07-14 | 2007-07-13 | Chitins and chitosans in an activated form and their slimming, hypoglycaemic, hypolipidaemic properties |
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
IT001373A ITMI20061373A1 (en) | 2006-07-14 | 2006-07-14 | GUITIN AND CHITOSANS IN ACTIVATED FORM AND THEIR PROPERTIES HYPOGLYCEMISAN AND HYPOLYPHEMISANTS |
ITMI2006A001373 | 2006-07-14 |
Publications (2)
Publication Number | Publication Date |
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WO2008010172A2 true WO2008010172A2 (en) | 2008-01-24 |
WO2008010172A3 WO2008010172A3 (en) | 2008-03-27 |
Family
ID=38957169
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
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PCT/IB2007/052803 WO2008010172A2 (en) | 2006-07-14 | 2007-07-13 | Chitins and chitosans in an activated form and their slimming, hypoglycaemic, hypolipidaemic properties |
Country Status (3)
Country | Link |
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EP (1) | EP2046838A2 (en) |
IT (1) | ITMI20061373A1 (en) |
WO (1) | WO2008010172A2 (en) |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2012022947A1 (en) * | 2010-08-17 | 2012-02-23 | Cmp Therapeutics Limited | Nutritional compositions comprising chitin microparticles |
Citations (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4125708A (en) * | 1977-02-15 | 1978-11-14 | The United States Of America As Represented By The Secretary Of Agriculture | Chitosan modified with anionic agent and glutaraldehyde |
US5993661A (en) * | 1997-04-14 | 1999-11-30 | The Research Foundation Of State University Of New York | Macroporous or microporous filtration membrane, method of preparation and use |
WO2001047372A2 (en) * | 1998-07-10 | 2001-07-05 | Vanson, Inc. | Absorbing fat chitosan |
WO2003011912A1 (en) * | 2001-08-02 | 2003-02-13 | Advanced Biopolymers As | Chitosan preparation |
EP1308177A1 (en) * | 2000-08-10 | 2003-05-07 | Osfarma, S.L. | Method for the production of chitosan-based films with enhanced cell adhering capacity, resulting product and applications |
EP1471149A1 (en) * | 1999-07-08 | 2004-10-27 | Food Industry Research and Development Institute | Production of chitosan and chitin |
-
2006
- 2006-07-14 IT IT001373A patent/ITMI20061373A1/en unknown
-
2007
- 2007-07-13 WO PCT/IB2007/052803 patent/WO2008010172A2/en active Application Filing
- 2007-07-13 EP EP07805146A patent/EP2046838A2/en not_active Withdrawn
Patent Citations (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4125708A (en) * | 1977-02-15 | 1978-11-14 | The United States Of America As Represented By The Secretary Of Agriculture | Chitosan modified with anionic agent and glutaraldehyde |
US5993661A (en) * | 1997-04-14 | 1999-11-30 | The Research Foundation Of State University Of New York | Macroporous or microporous filtration membrane, method of preparation and use |
WO2001047372A2 (en) * | 1998-07-10 | 2001-07-05 | Vanson, Inc. | Absorbing fat chitosan |
EP1471149A1 (en) * | 1999-07-08 | 2004-10-27 | Food Industry Research and Development Institute | Production of chitosan and chitin |
EP1308177A1 (en) * | 2000-08-10 | 2003-05-07 | Osfarma, S.L. | Method for the production of chitosan-based films with enhanced cell adhering capacity, resulting product and applications |
WO2003011912A1 (en) * | 2001-08-02 | 2003-02-13 | Advanced Biopolymers As | Chitosan preparation |
Cited By (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2012022947A1 (en) * | 2010-08-17 | 2012-02-23 | Cmp Therapeutics Limited | Nutritional compositions comprising chitin microparticles |
GB2495687A (en) * | 2010-08-17 | 2013-04-17 | Cmp Therapeuctics Ltd | Nutritional compositions comprising chitin microparticles |
CN103327831A (en) * | 2010-08-17 | 2013-09-25 | 姆柯瓦克斯有限公司 | Nutritional compositions comprising chitin microparticles |
Also Published As
Publication number | Publication date |
---|---|
WO2008010172A3 (en) | 2008-03-27 |
ITMI20061373A1 (en) | 2008-01-15 |
EP2046838A2 (en) | 2009-04-15 |
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