WO2000024785A1 - Substance utilisee pour la reduction du taux de cholesterol et de lipides - Google Patents

Substance utilisee pour la reduction du taux de cholesterol et de lipides Download PDF

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Publication number
WO2000024785A1
WO2000024785A1 PCT/FI1999/000885 FI9900885W WO0024785A1 WO 2000024785 A1 WO2000024785 A1 WO 2000024785A1 FI 9900885 W FI9900885 W FI 9900885W WO 0024785 A1 WO0024785 A1 WO 0024785A1
Authority
WO
WIPO (PCT)
Prior art keywords
substance
microcrystalline chitosan
cholesterol
reduction
lipids
Prior art date
Application number
PCT/FI1999/000885
Other languages
English (en)
Inventor
Henryk Struszczyk
Harri Pomoell
Marketta Wulff
Elina SÄYNÄTJOKI
Pauli Ylitalo
Erkki Wuolijoki
Harri HÄKLI
Original Assignee
Novasso Oy
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Novasso Oy filed Critical Novasso Oy
Priority to EP99954018A priority Critical patent/EP1144458A1/fr
Priority to JP2000578354A priority patent/JP2002528571A/ja
Priority to AU10486/00A priority patent/AU1048600A/en
Priority to CA002347967A priority patent/CA2347967A1/fr
Publication of WO2000024785A1 publication Critical patent/WO2000024785A1/fr

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
    • A61K31/715—Polysaccharides, i.e. having more than five saccharide radicals attached to each other by glycosidic linkages; Derivatives thereof, e.g. ethers, esters
    • 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
    • A23L33/20—Reducing nutritive value; Dietetic products with reduced nutritive value
    • A23L33/21—Addition of substantially indigestible substances, e.g. dietary fibres
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
    • A61K31/715—Polysaccharides, i.e. having more than five saccharide radicals attached to each other by glycosidic linkages; Derivatives thereof, e.g. ethers, esters
    • A61K31/716—Glucans
    • A61K31/722—Chitin, chitosan
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K33/00—Medicinal preparations containing inorganic active ingredients
    • A61K33/06—Aluminium, calcium or magnesium; Compounds thereof, e.g. clay
    • A61K33/10—Carbonates; Bicarbonates
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/06—Antihyperlipidemics
    • 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

  • the invention relates to a substance for reduction of serum cholesterol as well as lipids content in mammals, especially humans.
  • US-patent 4223023 discloses the use of standard chitosan as a food additive and an orally administrable preparation to reduce the absorption of lipids.
  • microcrystalline chitosan in a form of gel-like dispersion and/or powder characterized by average molecular weight higher than 1 ,000 daltons, preferably 10,000 to 300,000 daltons for reducing cholesterol and higher than 10,000 daltons, preferably 50,000 to 700,000 daltons for reducing lipids, and the deacetylation degree higher than 60 % is described in WO 98/34625.
  • This publication describes the general activity of microcrystalline chitosan for reduction of content of cholesterol and lipids.
  • the object of this invention is to effectively, specially and selectively reduce cholesterol as well as lipids content using microcrystalline chitosan.
  • the substance, in a suitable form to be administered orally is mainly characterized by two fractions of microcrystalline chitosan differing in average molecular weights. These fractions are present simultaneously in the same product which has been prepared by blending the two fractions, each having a characteristic molecular weight distribution and average value of its own.
  • the fraction with lower average molecular weight is responsible for the reduction of cholesterol level, especially the harmful LDL cholesterol, and the fraction with higher average molecular weight incorporated in the same formulation is responsible for the reduction of lipids. It is also possible that the fractions differ in other properties as well.
  • the microcrystalline chitosan in the product is combined with synergistic active substances to increase the cholesterol and lipids reduction.
  • microcrystalline chitosan present in at least two fractions is in a form of powder and/or gel-like dispersion and it is combined with synergistic active substances such as organic acids like ascorbic acid and/or carbonates like sodium carbonate, calcium carbonate and/or magnesium carbonate to improve the efficiency of substance in the body and to increase the cholesterol and lipids reduction.
  • synergistic active substances such as organic acids like ascorbic acid and/or carbonates like sodium carbonate, calcium carbonate and/or magnesium carbonate to improve the efficiency of substance in the body and to increase the cholesterol and lipids reduction.
  • microcrystalline chitosan is combined with synergistic active substances in a weight ratio ranged from 1 :0.001 to 0.001 :1 , preferably 1 :0.01 to 0.01 :1.
  • the polydispersity of the blended selected polymer fractions is lower than 4.0.
  • the first fraction has average molecular weight below 140 kD, preferably ranging from 20 to 140 kD for reduction of cholesterol content.
  • the second fraction has average molecular weight higher than 140 kD, preferably in the range of 160-400 kD and most preferably in the range of 200-400 kD for reduction of lipids content and is thus responsible for slimming effect.
  • the weight ratio of the two microcrystalline chitosan fractions ranges from 1 :99999 to 99999:1 , preferably from 1 :4999 to 4999:1.
  • the most practical embodiments have the ratios between 1:19 and 19:1 , preferably between 1 :9 and 9:1.
  • microcrystalline chitosan is combined with additives characterized by high synergistic action with this natural polymeric material that is able to form complexes with cholesterol and lipids.
  • the synergistic additives consisting of organic acids like ascorbic acid and/or suitable carbonates like sodium carbonate, calcium carbonate and/or magnesium carbonate in a presence of microcrystalline chitosan improve the special form of chitosan activity, protect the mammal organism system as well as protect against removal of the fat-soluble vitamins A and E.
  • Microcrystalline chitosan has a highly developed intrinsic surface, high positive charge and good ability to create hydrogen and ionic bonds and can form a complex with the synergistic active substances.
  • the carbonates contribute to the advantageous behaviour of the administered preparation in the gastrointestinal tract and keep the microcrystalline chitosan well dispersed in the stomach by releasing carbon dioxide upon contact with the acidic environment of the stomach. Further, by suitably choosing the balance between the various carbonates the pH of the preparation can be adjusted.
  • the selectivity of the rate of microcrystalline chitosan action for reduction of cholesterol and/or lipids according to the invention is connected with its fractional content as well as polydispersity degree lower than 4.0.
  • the first fraction of microcrystalline chitosan defined with viscometric average molecular weight as lying below 140 kD, preferably in a range of 20-140 kD, is subjected to faster enzymatic degradation producing suitable amount of oligoaminosaccharides with assumed structure and ability to combine at high rate with cholesterol, especially its low density fraction LDL (low density lipoprotein).
  • the second fraction of microcrystalline chitosan defined with viscometric average molecular weight to lie higher than 140 kD, preferably from 160 to 400 kD and most preferably in a range of 200-400 kD, is responsible for reduction of lipids content. Suitable ratio of above fractions in the microcrystalline chitosan used makes possible the selective, specific action against cholesterol on one hand and lipids on the other hand.
  • the substance according to the invention containing microcrystalline chitosan after 4 weeks of patient treatment has reduced the total cholesterol content more than 6 % and the LDL cholesterol more than 15 % in comparison to the initial levels.
  • the advantage of substance containing microcrystalline chitosan is connected with its variety of possible forms from powder to gel-like dispersion. It is not necessary to use a special diet together with the substance according to the invention.
  • the essential components of the substance can be included in an orally administrable unit together with a pharmaceutically accepetable carrier.
  • the substance can thus be in the form of a capsule, tablet or pill.
  • microcrystalline chitosan properties viscometric average molecular weight according to the method described in "Chitin”, Pergamon Press, Oxford, 1977 - deacetylation degree according to the method described in the “Cellulose Chemistry and Technology", vol. 11 , p. 633, 1977 polydispersity as well as fraction content according to the Gel Permeation Chromatography method.
  • 51 healthy females with body mass index ranging from 28.0 to 34.99 were subjected to in vivo test conducted according to the Declaration of Helsinki and Tokyo with trial plan reviewed by the local ethics committee. The trial was also conducted according to the Good Clinical Practice rules. The patients were asked to maintain their daily living routines including eating habits.
  • the identical capsules containing starch as placebo were used for comparison.
  • the procedure produced a daily dose of 2.4 g of microcrystalline chitosan to be taken in three capsules twice a day.
  • the same system was used for placebo.
  • microcrystalline chitosan powder characterized by viscometric average molecular weight of 300 kD, deacetylation degree of 84.7 % and polydispersity degree of 3.42 was blended with 99.9 weight parts of fraction of microcrystalline chitosan characterized by viscometric average molecular weight of 123 kD, deacetylation degree of 84.8. % and polydispersity degree of 3.67.
  • the blended microcrystalline chitosan powder was characterized by viscometric average molecular weight of 122 kD, deacetylation degree of 84,8 % and polydispersity degree of 3.65.
  • Example 3 400 mg of above blend with addition of 70 mg of active synergistic agents as in Example 1 were used in a form of capsules for reduction of cholesterol and lipids content. The procedure was as in Example 1. The patient characteristics as well as results of treatment after 8 weeks are presented in Table 3.
  • Vitamin A ( ⁇ M/l) before 2.44 ⁇ 0.4 2.31 ⁇ 0.3 after 2.41 ⁇ 0.3 2.29 ⁇ 0.3
  • Vitamin E ( ⁇ M/l) before 24.80 ⁇ 5.4 24.00 ⁇ 3.8 after 24.60 ⁇ 5.4 24.91 ⁇ 4.1
  • Raising the average molecular weight will result in still more lipids being absorbed, in the range 75 to 87 %, and the optimal range of Mw is between 200 and 400 kD.

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Epidemiology (AREA)
  • Engineering & Computer Science (AREA)
  • Molecular Biology (AREA)
  • Hematology (AREA)
  • Diabetes (AREA)
  • Inorganic Chemistry (AREA)
  • Food Science & Technology (AREA)
  • Obesity (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Nutrition Science (AREA)
  • Mycology (AREA)
  • Polymers & Plastics (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Organic Chemistry (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicinal Preparation (AREA)
  • Polysaccharides And Polysaccharide Derivatives (AREA)

Abstract

L'invention concerne une substance pour la réduction du taux de cholestérol et de lipides, à base de chitosane microcristallin sous forme de dispersion solide ou en gel. Le chitosane microcristallin sous forme de dispersion en poudre et/ou gel contient un mélange de deux fractions possédant des poids moléculaires différents, l'une réduisant le taux de cholestérol et l'autre le taux de lipides. Le chitosane cristallin est également combiné à des substances actives synergiques, telles que des acides organiques du type acide ascorbique et/ou des carbonates tels que du carbonate de sodium, du carbonate de calcium et/ou du carbonate de magnésium, pour l'augmentation du taux de cholestérol et la réduction du taux de lipides.
PCT/FI1999/000885 1998-10-23 1999-10-25 Substance utilisee pour la reduction du taux de cholesterol et de lipides WO2000024785A1 (fr)

Priority Applications (4)

Application Number Priority Date Filing Date Title
EP99954018A EP1144458A1 (fr) 1998-10-23 1999-10-25 Substance utilisee pour la reduction du taux de cholesterol et de lipides
JP2000578354A JP2002528571A (ja) 1998-10-23 1999-10-25 脂質およびコレステロール含有量低下のための物質
AU10486/00A AU1048600A (en) 1998-10-23 1999-10-25 Substance for reduction of cholesterol as well as lipids content
CA002347967A CA2347967A1 (fr) 1998-10-23 1999-10-25 Substance utilisee pour la reduction du taux de cholesterol et de lipides

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
FI982291 1998-10-23
FI982291A FI982291A (fi) 1998-10-23 1998-10-23 Aine kolesterolin sekä lipidien pitoisuuden alentamiseksi

Publications (1)

Publication Number Publication Date
WO2000024785A1 true WO2000024785A1 (fr) 2000-05-04

Family

ID=8552763

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/FI1999/000885 WO2000024785A1 (fr) 1998-10-23 1999-10-25 Substance utilisee pour la reduction du taux de cholesterol et de lipides

Country Status (7)

Country Link
EP (1) EP1144458A1 (fr)
JP (1) JP2002528571A (fr)
CN (1) CN1331703A (fr)
AU (1) AU1048600A (fr)
CA (1) CA2347967A1 (fr)
FI (1) FI982291A (fr)
WO (1) WO2000024785A1 (fr)

Cited By (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2002083104A1 (fr) * 2001-04-12 2002-10-24 Medicarb Ab Composition de matiere solide effervescente
ES2209632A1 (es) * 2002-08-30 2004-06-16 Romildo Holding, N.V. Complemento dietetico, soluble, efervescente y alimenticio.
KR100473445B1 (ko) * 2001-05-10 2005-03-08 씨제이 주식회사 저분자 키토산과 ε-폴리라이신을 주원료로 하는 콜레스테롤 저하제 및 건강 보조 식품
US6896902B2 (en) * 2001-04-12 2005-05-24 Medicarb Ab Effervescent solid composition of matter
WO2007068076A1 (fr) * 2005-12-16 2007-06-21 Dnp Canada Inc. Dérivés de chitine contre l'hyperlipémie
WO2008068763A2 (fr) * 2006-12-07 2008-06-12 Ben-Bar Technology 2006 Ltd. Mélange et procédé pour réduire le cholestérol en utilisant des microparticules hydrophobes
EP2016946A1 (fr) * 2007-07-18 2009-01-21 The Jordanian Pharmaceutical Manufacturing Co. Composition de coprécipité de chotisane et de dioxyde de silicium pour une utilisation en tant qu'agent thérapeutique
US8168767B2 (en) 2010-06-18 2012-05-01 Halosource, Inc. Formulations and methods for solid chitosan-containing blends

Families Citing this family (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20060058261A1 (en) * 2004-09-15 2006-03-16 Andre Aube Chitin derivatives for hyperlipidemia
CN102504291B (zh) * 2011-10-28 2014-01-01 北京联合大学生物化学工程学院 pH敏感型壳聚糖交联聚维酮凝胶及其制备方法和应用
CN115568321B (zh) * 2022-09-16 2024-04-02 江苏省农业科学院 一种延长苏翠1号梨叶片生理功能期的方法

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4223023A (en) * 1978-10-12 1980-09-16 Ivan Furda Nonabsorbable lipid binder
WO1991000298A1 (fr) * 1989-06-30 1991-01-10 Firextra Oy Methode pour la fabrication continue de chitosan microcristallin
JPH06205698A (ja) * 1992-11-24 1994-07-26 Asahi Shokuhin Kogyo Kk キトサンおよび／またはその部分分解物の分子量分布測定方法
WO1998034625A1 (fr) * 1997-02-06 1998-08-13 Novasso Oy Substance aux fins de la reduction de teneurs en lipides et en cholesterol et technique afferente

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4223023A (en) * 1978-10-12 1980-09-16 Ivan Furda Nonabsorbable lipid binder
WO1991000298A1 (fr) * 1989-06-30 1991-01-10 Firextra Oy Methode pour la fabrication continue de chitosan microcristallin
JPH06205698A (ja) * 1992-11-24 1994-07-26 Asahi Shokuhin Kogyo Kk キトサンおよび／またはその部分分解物の分子量分布測定方法
WO1998034625A1 (fr) * 1997-02-06 1998-08-13 Novasso Oy Substance aux fins de la reduction de teneurs en lipides et en cholesterol et technique afferente

Non-Patent Citations (3)

* Cited by examiner, † Cited by third party
Title
CHITIN WORLD (PROC. INT. CONF. CHITIN CHITOSAN), 6TH, 1994, pages 594 - 599 *
DATABASE CAPLUS [online] STRUSZCZYK HENRYK ET AL.: "Present state and forecast of microcrystalline chitosan", XP002947424, accession no. STN Database accession no. 1996:380820 *
DATABASE WPI Week 199434, Derwent World Patents Index; AN 1994-275530, XP002947423, "Measurement of distribution of molecular wt of chitosan and/or its partially decomposed prod - by fractionating two or more fractions of different mol wts using gel filtration, treating with chitosan-decomposing" *

Cited By (12)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2002083104A1 (fr) * 2001-04-12 2002-10-24 Medicarb Ab Composition de matiere solide effervescente
AU2002251662B2 (en) * 2001-04-12 2005-04-21 Medicarb Ab An effervescent solid composition of matter
US6896902B2 (en) * 2001-04-12 2005-05-24 Medicarb Ab Effervescent solid composition of matter
US7153492B2 (en) 2001-04-12 2006-12-26 Medicarb Ab Effervescent solid composition of matter
KR100473445B1 (ko) * 2001-05-10 2005-03-08 씨제이 주식회사 저분자 키토산과 ε-폴리라이신을 주원료로 하는 콜레스테롤 저하제 및 건강 보조 식품
ES2209632A1 (es) * 2002-08-30 2004-06-16 Romildo Holding, N.V. Complemento dietetico, soluble, efervescente y alimenticio.
WO2007068076A1 (fr) * 2005-12-16 2007-06-21 Dnp Canada Inc. Dérivés de chitine contre l'hyperlipémie
WO2008068763A2 (fr) * 2006-12-07 2008-06-12 Ben-Bar Technology 2006 Ltd. Mélange et procédé pour réduire le cholestérol en utilisant des microparticules hydrophobes
WO2008068763A3 (fr) * 2006-12-07 2008-07-24 Ben Bar Technology 2006 Mélange et procédé pour réduire le cholestérol en utilisant des microparticules hydrophobes
EP2016946A1 (fr) * 2007-07-18 2009-01-21 The Jordanian Pharmaceutical Manufacturing Co. Composition de coprécipité de chotisane et de dioxyde de silicium pour une utilisation en tant qu'agent thérapeutique
US8168767B2 (en) 2010-06-18 2012-05-01 Halosource, Inc. Formulations and methods for solid chitosan-containing blends
US8357787B2 (en) 2010-06-18 2013-01-22 Halosource, Inc. Formulations and methods for solid chitosan-containing blends

Also Published As

Publication number Publication date
AU1048600A (en) 2000-05-15
CN1331703A (zh) 2002-01-16
FI982291A (fi) 2000-04-24
EP1144458A1 (fr) 2001-10-17
FI982291A0 (fi) 1998-10-23
JP2002528571A (ja) 2002-09-03
CA2347967A1 (fr) 2000-05-04

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