CA2347967A1 - Substance for reduction of cholesterol as well as lipids content - Google Patents
Substance for reduction of cholesterol as well as lipids content Download PDFInfo
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- CA2347967A1 CA2347967A1 CA002347967A CA2347967A CA2347967A1 CA 2347967 A1 CA2347967 A1 CA 2347967A1 CA 002347967 A CA002347967 A CA 002347967A CA 2347967 A CA2347967 A CA 2347967A CA 2347967 A1 CA2347967 A1 CA 2347967A1
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- Prior art keywords
- substance
- cholesterol
- microcrystalline chitosan
- reduction
- lipids
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- 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 title claims abstract description 61
- 235000012000 cholesterol Nutrition 0.000 title claims abstract description 28
- 150000002632 lipids Chemical class 0.000 title claims abstract description 27
- 239000000126 substance Substances 0.000 title claims abstract description 21
- 229920001661 Chitosan Polymers 0.000 claims abstract description 51
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 claims abstract description 12
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 claims abstract description 10
- 239000000843 powder Substances 0.000 claims abstract description 10
- 239000000203 mixture Substances 0.000 claims abstract description 9
- 230000002195 synergetic effect Effects 0.000 claims abstract description 9
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 claims abstract description 8
- 239000006185 dispersion Substances 0.000 claims abstract description 8
- 239000013543 active substance Substances 0.000 claims abstract description 7
- 229910000019 calcium carbonate Inorganic materials 0.000 claims abstract description 6
- 150000004649 carbonic acid derivatives Chemical class 0.000 claims abstract description 6
- ZLNQQNXFFQJAID-UHFFFAOYSA-L magnesium carbonate Chemical compound [Mg+2].[O-]C([O-])=O ZLNQQNXFFQJAID-UHFFFAOYSA-L 0.000 claims abstract description 6
- 239000001095 magnesium carbonate Substances 0.000 claims abstract description 6
- 229910000021 magnesium carbonate Inorganic materials 0.000 claims abstract description 6
- 229910000029 sodium carbonate Inorganic materials 0.000 claims abstract description 5
- 229960005070 ascorbic acid Drugs 0.000 claims abstract description 4
- 235000010323 ascorbic acid Nutrition 0.000 claims abstract description 4
- 239000011668 ascorbic acid Substances 0.000 claims abstract description 4
- 229940093915 gynecological organic acid Drugs 0.000 claims abstract description 4
- 150000007524 organic acids Chemical class 0.000 claims abstract description 4
- 235000005985 organic acids Nutrition 0.000 claims abstract description 4
- 239000007787 solid Substances 0.000 claims abstract 2
- 239000002775 capsule Substances 0.000 claims description 6
- 230000000694 effects Effects 0.000 claims description 6
- 239000006187 pill Substances 0.000 claims description 2
- 229920000642 polymer Polymers 0.000 claims description 2
- 239000003826 tablet Substances 0.000 claims description 2
- 239000000902 placebo Substances 0.000 description 9
- 229940068196 placebo Drugs 0.000 description 9
- 238000000034 method Methods 0.000 description 7
- 230000006196 deacetylation Effects 0.000 description 5
- 238000003381 deacetylation reaction Methods 0.000 description 5
- 235000019155 vitamin A Nutrition 0.000 description 5
- 239000011719 vitamin A Substances 0.000 description 5
- 235000019165 vitamin E Nutrition 0.000 description 5
- 239000011709 vitamin E Substances 0.000 description 5
- 108010007622 LDL Lipoproteins Proteins 0.000 description 4
- 102000007330 LDL Lipoproteins Human genes 0.000 description 4
- GVJHHUAWPYXKBD-UHFFFAOYSA-N d-alpha-tocopherol Natural products OC1=C(C)C(C)=C2OC(CCCC(C)CCCC(C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-UHFFFAOYSA-N 0.000 description 4
- 238000009472 formulation Methods 0.000 description 4
- 230000003247 decreasing effect Effects 0.000 description 3
- 238000002360 preparation method Methods 0.000 description 3
- FPIPGXGPPPQFEQ-UHFFFAOYSA-N 13-cis retinol Natural products OCC=C(C)C=CC=C(C)C=CC1=C(C)CCCC1(C)C FPIPGXGPPPQFEQ-UHFFFAOYSA-N 0.000 description 2
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 2
- 238000008214 LDL Cholesterol Methods 0.000 description 2
- 241000124008 Mammalia Species 0.000 description 2
- FPIPGXGPPPQFEQ-BOOMUCAASA-N Vitamin A Natural products OC/C=C(/C)\C=C\C=C(\C)/C=C/C1=C(C)CCCC1(C)C FPIPGXGPPPQFEQ-BOOMUCAASA-N 0.000 description 2
- 229930003427 Vitamin E Natural products 0.000 description 2
- 239000000654 additive Substances 0.000 description 2
- FPIPGXGPPPQFEQ-OVSJKPMPSA-N all-trans-retinol Chemical compound OC\C=C(/C)\C=C\C=C(/C)\C=C\C1=C(C)CCCC1(C)C FPIPGXGPPPQFEQ-OVSJKPMPSA-N 0.000 description 2
- 235000014113 dietary fatty acids Nutrition 0.000 description 2
- 239000000194 fatty acid Substances 0.000 description 2
- 229930195729 fatty acid Natural products 0.000 description 2
- 150000004665 fatty acids Chemical class 0.000 description 2
- 235000013373 food additive Nutrition 0.000 description 2
- 239000002778 food additive Substances 0.000 description 2
- WIGCFUFOHFEKBI-UHFFFAOYSA-N gamma-tocopherol Natural products CC(C)CCCC(C)CCCC(C)CCCC1CCC2C(C)C(O)C(C)C(C)C2O1 WIGCFUFOHFEKBI-UHFFFAOYSA-N 0.000 description 2
- 210000002966 serum Anatomy 0.000 description 2
- 210000002784 stomach Anatomy 0.000 description 2
- 239000012747 synergistic agent Substances 0.000 description 2
- 235000013343 vitamin Nutrition 0.000 description 2
- 239000011782 vitamin Substances 0.000 description 2
- 229930003231 vitamin Natural products 0.000 description 2
- 229940088594 vitamin Drugs 0.000 description 2
- 229940046009 vitamin E Drugs 0.000 description 2
- 229940045997 vitamin a Drugs 0.000 description 2
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 1
- 208000024172 Cardiovascular disease Diseases 0.000 description 1
- 229920002101 Chitin Polymers 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- 108010023302 HDL Cholesterol Proteins 0.000 description 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
- 108010028554 LDL Cholesterol Proteins 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 239000001569 carbon dioxide Substances 0.000 description 1
- 229910002092 carbon dioxide Inorganic materials 0.000 description 1
- 239000001913 cellulose Substances 0.000 description 1
- 229920002678 cellulose Polymers 0.000 description 1
- 239000003638 chemical reducing agent Substances 0.000 description 1
- -1 cholesterol triglycerides Chemical class 0.000 description 1
- 238000012790 confirmation Methods 0.000 description 1
- 235000005911 diet Nutrition 0.000 description 1
- 230000037213 diet Effects 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 235000006694 eating habits Nutrition 0.000 description 1
- 230000007515 enzymatic degradation Effects 0.000 description 1
- 235000002535 fat free diet Nutrition 0.000 description 1
- 235000013305 food Nutrition 0.000 description 1
- 210000001035 gastrointestinal tract Anatomy 0.000 description 1
- 238000005227 gel permeation chromatography Methods 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 235000015263 low fat diet Nutrition 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 229920001282 polysaccharide Polymers 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 150000003722 vitamin derivatives Chemical class 0.000 description 1
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
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- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Engineering & Computer Science (AREA)
- Molecular Biology (AREA)
- Hematology (AREA)
- Diabetes (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Obesity (AREA)
- Nutrition Science (AREA)
- General Chemical & Material Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Mycology (AREA)
- Polymers & Plastics (AREA)
- Food Science & Technology (AREA)
- Inorganic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicinal Preparation (AREA)
- Polysaccharides And Polysaccharide Derivatives (AREA)
Abstract
The invention relates to a substance for reduction of cholesterol as well as lipids content based on the microcrystalline chitosan in a form of solid or gel-like dispersion. The microcrystalline chitosan in a form of powder and/or gel-like dispersion contains a blend of two fractions having differing molecular weights, one reducing the cholesterol (LDL) content and the other reducing the lipids content. The microcrystalline chitosan is further 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 increase the cholesterol and lipids reduction.
Description
Substance for reduction of cholesterol as well as lipids content The invention relates to a substance for reduction of serum cholesterol as well as lipids content in mammals, especially humans.
The problem caused by lipids and chloesterol to human health are known, such as overweight problems and cardiovascular diseases.
Many atternpts have been made to reduce the negative effect of lipids and cholesterol contained in the food. One alternative is a special low-fat or fat-free diet. Another solution has been the administration of special drugs or use of special food additives.
US-patent 4223023 discloses the use of standard chitosan as a food additive and an orally administrable preparation to reduce the absorption of lipids.
The reduction of lipids and cholesterol by microcrystalline chitosan in a form of gel-like dispersion and/or powder characterized by average molecular weight highE;r 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 deacetyiation degree higher than 60 % is described in WO 98/34Ei25. This publication describes the general activity of microcrystalline chitosan far reduction of content of cholesterol and lipids.
All well-known slimming or cholesterol reducing agents based on chitosan are non-selective for their activity as well as efficiency of action.
The object of this invention is to effectively, specially and selectively reduce cholesterol as well as lipids content using microcrystalline chitosan. For achieving i:he objects 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 CONFIRMATION COPY
The problem caused by lipids and chloesterol to human health are known, such as overweight problems and cardiovascular diseases.
Many atternpts have been made to reduce the negative effect of lipids and cholesterol contained in the food. One alternative is a special low-fat or fat-free diet. Another solution has been the administration of special drugs or use of special food additives.
US-patent 4223023 discloses the use of standard chitosan as a food additive and an orally administrable preparation to reduce the absorption of lipids.
The reduction of lipids and cholesterol by microcrystalline chitosan in a form of gel-like dispersion and/or powder characterized by average molecular weight highE;r 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 deacetyiation degree higher than 60 % is described in WO 98/34Ei25. This publication describes the general activity of microcrystalline chitosan far reduction of content of cholesterol and lipids.
All well-known slimming or cholesterol reducing agents based on chitosan are non-selective for their activity as well as efficiency of action.
The object of this invention is to effectively, specially and selectively reduce cholesterol as well as lipids content using microcrystalline chitosan. For achieving i:he objects 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 CONFIRMATION COPY
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. According to an advantageous embodiment the microcrystalline chitosan in the product is combined with synergistic active substances to increase the cholesterol and lipids reduction.
The 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 :>odium carbonate, calcium carbonate and/or magnesium carbonate to improve the efficiency of substance in the body and to increase the cholesterol and lipids reduction.
According to a preferred embodiment of the invention the 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 O.t)1:1.
According to a preferred embodiment of the invention the poiydispersity of the blended selected polymer fractions is lower than 4Ø The first fraction has average molecular weight below 140 kD, preferably ranging frorn 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 microcrystailine 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.
The microcrystalline chitasan 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 andlor 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 microcrystaliine 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 microcrystaliine 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 4Ø The first fraction of microcrystalline chitosan, defined with viscometric average molecular weight as lying below 140 kD, preferably iin 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 iits 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 prefE;rably 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.
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. According to an advantageous embodiment the microcrystalline chitosan in the product is combined with synergistic active substances to increase the cholesterol and lipids reduction.
The 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 :>odium carbonate, calcium carbonate and/or magnesium carbonate to improve the efficiency of substance in the body and to increase the cholesterol and lipids reduction.
According to a preferred embodiment of the invention the 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 O.t)1:1.
According to a preferred embodiment of the invention the poiydispersity of the blended selected polymer fractions is lower than 4Ø The first fraction has average molecular weight below 140 kD, preferably ranging frorn 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 microcrystailine 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.
The microcrystalline chitasan 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 andlor 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 microcrystaliine 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 microcrystaliine 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 4Ø The first fraction of microcrystalline chitosan, defined with viscometric average molecular weight as lying below 140 kD, preferably iin 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 iits 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 prefE;rably 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.
The following methods were used for the determination of microcrystalline chitosan properties:
- viscometric average molecular weight according to the method described in "Chitin", Pergamon Press, Oxford, - deacetylation degree according to the method described in the "Cellulose Chemistry and Technology", vol. 11, p. 633, - polydispersit)/ as well as fraction content according to the Gel Permeation Chromatography method.
The contents of total cholesterol, LDL as well as HDL cholesterol triglycerides as well as vitamin A and E were determined according to the standards.
The invention is explained further in the following examples which do not restrict the scope of claims.
Example 1.
The capsules based on hard gelatin with 400 mg of microcrystalline chitosan powder characterized by viscometric average molecular weight of 137 kD, deac;etylation degree of 76 % and polydispersity degree of :3.84 and 70 nng of active synergistic agent including 3.8 mg of ascorbic; acid, 18.8 rng of sodium carbonate, 25.8 mg of calcium carbonate and 21.6 rnc~ of magnesium carbonate were used for reduction of cholesterol and lipids content. 51 healthy females with body mass index rangirng 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 systE~m was used for placebo. The patient characteristic is presented in Table 1.
Table 1. Patients characteristic before treatment (data given as means t SD) Patient Treatment group Chitosan/range Placebo/range Totals Number 24 27 51 Age (year) 41.4 7.F3 l 41.3 7.1 / 41.3 24-57 19-55 7.3 Height (cm) 165.1 165.2 165.1 Weight (kg) 83.33 9.2 / 84.63 7.8 84 71-105 / 71-101 8.4 Body mass 30.39 : 2.1 30.81 2.2 30.61 index / 28-35 / 28-35 2 fs-chol.tot.5.55 0.9 5.48 0.8 5.51 (mmol/l) 0.9 fs-HDL (mmol/I)1.33 0.;3 1.34 0.4 1.37 0.4 fs-Trigl. 1.24 O.E3 1.40 0.6 1.33 (mmol/I) 0.6 fs-LDL (mmol/I)3.65 0.9 3.45 0.7 3.55 0.8 The treatment parameters after 4 weeks are presented in Table 2.
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.
The following methods were used for the determination of microcrystalline chitosan properties:
- viscometric average molecular weight according to the method described in "Chitin", Pergamon Press, Oxford, - deacetylation degree according to the method described in the "Cellulose Chemistry and Technology", vol. 11, p. 633, - polydispersit)/ as well as fraction content according to the Gel Permeation Chromatography method.
The contents of total cholesterol, LDL as well as HDL cholesterol triglycerides as well as vitamin A and E were determined according to the standards.
The invention is explained further in the following examples which do not restrict the scope of claims.
Example 1.
The capsules based on hard gelatin with 400 mg of microcrystalline chitosan powder characterized by viscometric average molecular weight of 137 kD, deac;etylation degree of 76 % and polydispersity degree of :3.84 and 70 nng of active synergistic agent including 3.8 mg of ascorbic; acid, 18.8 rng of sodium carbonate, 25.8 mg of calcium carbonate and 21.6 rnc~ of magnesium carbonate were used for reduction of cholesterol and lipids content. 51 healthy females with body mass index rangirng 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 systE~m was used for placebo. The patient characteristic is presented in Table 1.
Table 1. Patients characteristic before treatment (data given as means t SD) Patient Treatment group Chitosan/range Placebo/range Totals Number 24 27 51 Age (year) 41.4 7.F3 l 41.3 7.1 / 41.3 24-57 19-55 7.3 Height (cm) 165.1 165.2 165.1 Weight (kg) 83.33 9.2 / 84.63 7.8 84 71-105 / 71-101 8.4 Body mass 30.39 : 2.1 30.81 2.2 30.61 index / 28-35 / 28-35 2 fs-chol.tot.5.55 0.9 5.48 0.8 5.51 (mmol/l) 0.9 fs-HDL (mmol/I)1.33 0.;3 1.34 0.4 1.37 0.4 fs-Trigl. 1.24 O.E3 1.40 0.6 1.33 (mmol/I) 0.6 fs-LDL (mmol/I)3.65 0.9 3.45 0.7 3.55 0.8 The treatment parameters after 4 weeks are presented in Table 2.
Table 2. Treatment parameters after 4 weeks Parameter Chitosan Placebo Number of patients24 27 fs-chol.tot. 5.23 + 0.8 5.41 + 0.8 (mmoi/I) difference - 0.32 - 0.07 fs-HDL (mmol/I)1.48 + 0.4 1.54 + 0.5 difference + 0.15. + 0.14 fs-LDL (mmol/I)3.18 0.8 3.27 0.7 difference - 0.47 - 0.18 fs-Trigl. (mmol/I)1.26 + 0.6 1.34 + 0.8 difference + 0.2 - 0.06 As the result of 4 weeks long test the serum mean total cholesterol decreased for the patients treated by microcrystalline chitosan by 0.32 mmol/I, whereas witlh the placebo group only by 0.07 mmol/l. The low density cholesterol (LDL) for microcrystalline chitosan treated group was reduced by 0.48 nnmol/I, whereas for the placebo group by 0.18 mmol/I only.
Example 2.
0.1 weight parts of microcrystalline chitosan powder characterized by viscometric average molE:cular weight of 300 kD, deacetylation degree of 84.7 % and polydispe~rsity 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. 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 trE~atment after 8 weeks are presented in Table 3.
Table 3. 'The patient characteristics and treatment parameters after 8 weeks Parameter Chitosan Placebo before after before affer Number of 11 11 14 14 patients Age, years 38 8 - 44 5 -Height, cm 165 7 - 165 6 -Body mass 32 2 32 2 33 2 33 2 index fs-chol.tot.5.75 1.0 5.37 0.9 5.41 0.6 5.19 (mmol/I) 0.8 difference - - 0.38 - - 0.22 fs-HDL (mmol/I;I1.43 0.291.45 -~ 1.27 0.43 1.36 0.32 0.51 difference - + 0.02 - + 0.09 fs-LDL (mmol/I)3.79 0.943.49 0.64 3.31 0.82 3.23 0.79 difference - - 0.30 - - 0.08 fs-Trigl. 1.20 0.4!51.40 0:39 1.33 0.49 1.33 (mmol/I) 0.43 difference - + 0.2 - 0 As the result of 8 weeks long test, the serum total cholesterol decreased for the patients treated with microcrystalline chitosan by 0.38 mmol/I whereas with the placebo group only by 0.22 mmol/l. The low density cholesterol of LDL for the first group decreased by 0.30 mmol/I whereas for the second group by 0.08 mmol/l only. At the same time the fat solublE~ vitamins A and E were analyzed before trial as well as after 8 weeks of trial. The results of this test are presented in Table 4.
Table 4. The fat soluble vitamins A and E
WO 00/24785 $ PCT/FI99/00885 Type of vitamins Chitosan treatment Placebo treatment Vitamin A (wM/i) before 2.44 ~ 0.4 2.31 ~ 0.3 after 2.41 ~ 0.3 2.29 ~ 0.3 Vitamin E (pM/l) before 24.80 ~ 5.4 24.00 ~ 3.8 after 24.60 ~ 5.4 24.91 ~ 4.1 The results of fat soluble vitamin tests confirm that the used microcrystalline chitosan is fully safe as for their contents.
Example 3.
Several samples of microcrystalline chitosan (MCCh) powder with a dry weight of 0.15 g and with similar deacetylation degree of DD = 80-85 %, characterized by viscometric average molecular weight in a range of Mw = 20-180 kD as well as the MCCh formulation with composition presented in Example 1 with viscometric average molecular weight of 7 30 kD and with a dry MCCh weight of 0.15 g, and a commercially available "fat blocker" containing standard chitosan with DD = 74 % and Mw = 125 kD were used for a test of the fat binding effectivity according to the modified method described by S. Demarger-Andre and A. Domard in Carbohydrate Polymers 22 (1993) 117-126.
The fat binding effectivity calculated as the percentage of total fat bound in comparison to initial fatty acids, is presented in following Table 5.
Table 5. Fat binding e~ffectivity for different chitosan forms Type of chitosan Mw Fatty acids binding effectivity kD
MCCh 20 44.4 MCCh 165 54.2 MCCh 145 57.0 MCCh 180 52.6 MCCh formulation 130 31.8 Commercial "fat blocker"125 17.6 with standard chitosan The presented results of the test show that the total fat binding effectivity expresses the action of the MCCh in relation to its average molecular weight. MCCh formulation with composition as in Example 1 has presented the total fat binding effectivity higher than 81 %, in comparison to the commercially available "fat blocker" containing standard chitosan.
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 kC~.
Example 2.
0.1 weight parts of microcrystalline chitosan powder characterized by viscometric average molE:cular weight of 300 kD, deacetylation degree of 84.7 % and polydispe~rsity 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. 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 trE~atment after 8 weeks are presented in Table 3.
Table 3. 'The patient characteristics and treatment parameters after 8 weeks Parameter Chitosan Placebo before after before affer Number of 11 11 14 14 patients Age, years 38 8 - 44 5 -Height, cm 165 7 - 165 6 -Body mass 32 2 32 2 33 2 33 2 index fs-chol.tot.5.75 1.0 5.37 0.9 5.41 0.6 5.19 (mmol/I) 0.8 difference - - 0.38 - - 0.22 fs-HDL (mmol/I;I1.43 0.291.45 -~ 1.27 0.43 1.36 0.32 0.51 difference - + 0.02 - + 0.09 fs-LDL (mmol/I)3.79 0.943.49 0.64 3.31 0.82 3.23 0.79 difference - - 0.30 - - 0.08 fs-Trigl. 1.20 0.4!51.40 0:39 1.33 0.49 1.33 (mmol/I) 0.43 difference - + 0.2 - 0 As the result of 8 weeks long test, the serum total cholesterol decreased for the patients treated with microcrystalline chitosan by 0.38 mmol/I whereas with the placebo group only by 0.22 mmol/l. The low density cholesterol of LDL for the first group decreased by 0.30 mmol/I whereas for the second group by 0.08 mmol/l only. At the same time the fat solublE~ vitamins A and E were analyzed before trial as well as after 8 weeks of trial. The results of this test are presented in Table 4.
Table 4. The fat soluble vitamins A and E
WO 00/24785 $ PCT/FI99/00885 Type of vitamins Chitosan treatment Placebo treatment Vitamin A (wM/i) before 2.44 ~ 0.4 2.31 ~ 0.3 after 2.41 ~ 0.3 2.29 ~ 0.3 Vitamin E (pM/l) before 24.80 ~ 5.4 24.00 ~ 3.8 after 24.60 ~ 5.4 24.91 ~ 4.1 The results of fat soluble vitamin tests confirm that the used microcrystalline chitosan is fully safe as for their contents.
Example 3.
Several samples of microcrystalline chitosan (MCCh) powder with a dry weight of 0.15 g and with similar deacetylation degree of DD = 80-85 %, characterized by viscometric average molecular weight in a range of Mw = 20-180 kD as well as the MCCh formulation with composition presented in Example 1 with viscometric average molecular weight of 7 30 kD and with a dry MCCh weight of 0.15 g, and a commercially available "fat blocker" containing standard chitosan with DD = 74 % and Mw = 125 kD were used for a test of the fat binding effectivity according to the modified method described by S. Demarger-Andre and A. Domard in Carbohydrate Polymers 22 (1993) 117-126.
The fat binding effectivity calculated as the percentage of total fat bound in comparison to initial fatty acids, is presented in following Table 5.
Table 5. Fat binding e~ffectivity for different chitosan forms Type of chitosan Mw Fatty acids binding effectivity kD
MCCh 20 44.4 MCCh 165 54.2 MCCh 145 57.0 MCCh 180 52.6 MCCh formulation 130 31.8 Commercial "fat blocker"125 17.6 with standard chitosan The presented results of the test show that the total fat binding effectivity expresses the action of the MCCh in relation to its average molecular weight. MCCh formulation with composition as in Example 1 has presented the total fat binding effectivity higher than 81 %, in comparison to the commercially available "fat blocker" containing standard chitosan.
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 kC~.
Claims (10)
1. Substance for reduction of cholesterol as well as lipids content based on the microcrystalline chitosan in a form of solid or gel-like dispersion, characterized in that the microcrystalline chitosan used in a form of powder and/or gel-like dispersion contains a blend of at least two fractions having differing average molecular weights.
2. Substance as claimed in claim 1, characterized in that the blended selected polymer fractions have a polydispersity degree lower than 4Ø
3. Substance as claimed in claim 1 or 2, characterized in that the first fraction has average molecular weight below 140 kD, preferably ranging from 20 to 140 kD, to create the reduction of cholesterol content, and the second fraction has average molecular weight above 140 kD, preferably between 160 and 400 kD and most preferably in a range of 200-400 kD to reduce lipids content responsible for slimming effect.
4. Substance as claimed in any of claims 1 to 3, characterized in that the microcrystalline chitosan in a form of powder and/or gel-like dispersion 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 increase the cholesterol and lipids reduction.
5. Substance as claimed in claim 4, characterized in that the microcrystalline chitosan is combined with sodium carbonate, calcium carbonate and magnesium carbonate.
6. Substance as claimed in any of claims 1 to 5, characterized in that the weight ratio of the two microcrystalline chitosan fractions ranges from 1:99999 to 99999:1.
7. Substance as claimed in claim 6, characterized in that the weight ratio of the two microcrystalline chitosan fractions ranges from 1:4999 to 4999:1.
8. Substance as claimed in claim 7, characterized in that the weight ratio of the two microcrystalline chitosan fractions ranges from 1:19 to 19:1, preferably from 1:9 to 9:1.
9. Substance as claimed in any of the preceding claims, characterized in that the microcrystalline chitosan is combined with synergistic active substance in a weight ration ranging from 1:0.001 to 0.001:1, preferably 1:0.01 to 0.01:1.
10. Substance as claimed in any of the preceding claims, characterized in that it is in form of an orally administrable capsule, tablet or pill.
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
FI982291A FI982291A (en) | 1998-10-23 | 1998-10-23 | An agent for lowering cholesterol and lipids |
FI982291 | 1998-10-23 | ||
PCT/FI1999/000885 WO2000024785A1 (en) | 1998-10-23 | 1999-10-25 | Substance for reduction of cholesterol as well as lipids content |
Publications (1)
Publication Number | Publication Date |
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CA2347967A1 true CA2347967A1 (en) | 2000-05-04 |
Family
ID=8552763
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CA002347967A Abandoned CA2347967A1 (en) | 1998-10-23 | 1999-10-25 | Substance for reduction of cholesterol as well as lipids content |
Country Status (7)
Country | Link |
---|---|
EP (1) | EP1144458A1 (en) |
JP (1) | JP2002528571A (en) |
CN (1) | CN1331703A (en) |
AU (1) | AU1048600A (en) |
CA (1) | CA2347967A1 (en) |
FI (1) | FI982291A (en) |
WO (1) | WO2000024785A1 (en) |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2006029524A1 (en) * | 2004-09-15 | 2006-03-23 | Magistral Biotech Inc. | Combination of polychitosamine and hmg-coa reductase inhibitor for hyperlipidemia |
Families Citing this family (10)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
AU2002251662B2 (en) * | 2001-04-12 | 2005-04-21 | Medicarb Ab | An effervescent solid composition of matter |
SE522529C2 (en) * | 2001-04-12 | 2004-02-17 | Medicarb Ab | Effervescent solid composition used for treating dermal wounds comprises chitosan or component releasing carbon dioxide in acidic environment |
KR100473445B1 (en) * | 2001-05-10 | 2005-03-08 | 씨제이 주식회사 | cholesterol reducer and health food containing chitosan and ε-polylysine |
ES2209632B1 (en) * | 2002-08-30 | 2005-08-01 | Romildo Holding, N.V. | DIETETIC, SOLUBLE, EFFECTIVE AND FOOD COMPLEMENT. |
ZA200806192B (en) * | 2005-12-16 | 2009-12-30 | Dpn Canada Inc | Chitin derivatives for hyperlipidemia |
WO2008068763A2 (en) * | 2006-12-07 | 2008-06-12 | Ben-Bar Technology 2006 Ltd. | Mixture and method for reducing cholesterol using hydrophobic chitosan microparticles |
EP2016946B1 (en) * | 2007-07-18 | 2013-02-27 | The Jordanian Pharmaceutical Manufacturing Co. | Chitosan silicon dioxide coprecipitate composition for use as a therapeutically active agent |
CN102469782A (en) | 2010-06-18 | 2012-05-23 | 哈洛资源公司 | Formulations and methods for solid chitosan-containing blends |
CN102504291B (en) * | 2011-10-28 | 2014-01-01 | 北京联合大学生物化学工程学院 | pH sensitive type chitosan crosslinking povidone gel and preparation method and application thereof |
CN115568321B (en) * | 2022-09-16 | 2024-04-02 | 江苏省农业科学院 | Method for prolonging physiological function period of leaf of Su Cui No. 1 pear |
Family Cites Families (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4223023A (en) * | 1978-10-12 | 1980-09-16 | Ivan Furda | Nonabsorbable lipid binder |
FI83426C (en) * | 1989-06-30 | 1991-07-10 | Firextra Oy | FOERFARANDE FOER KONTINUERLIG FRAMSTAELLNING AV MICROCRYSTALLINE KITOSAN. |
JPH07100040B2 (en) * | 1992-11-24 | 1995-11-01 | 朝日食品工業株式会社 | Method for measuring molecular weight distribution of chitosan and / or partially decomposed product thereof |
FI107432B (en) * | 1997-02-06 | 2001-08-15 | Novasso Oy | Use of microcrystalline chitosan |
-
1998
- 1998-10-23 FI FI982291A patent/FI982291A/en unknown
-
1999
- 1999-10-25 WO PCT/FI1999/000885 patent/WO2000024785A1/en not_active Application Discontinuation
- 1999-10-25 CN CN99814701A patent/CN1331703A/en active Pending
- 1999-10-25 EP EP99954018A patent/EP1144458A1/en not_active Withdrawn
- 1999-10-25 JP JP2000578354A patent/JP2002528571A/en active Pending
- 1999-10-25 CA CA002347967A patent/CA2347967A1/en not_active Abandoned
- 1999-10-25 AU AU10486/00A patent/AU1048600A/en not_active Abandoned
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2006029524A1 (en) * | 2004-09-15 | 2006-03-23 | Magistral Biotech Inc. | Combination of polychitosamine and hmg-coa reductase inhibitor for hyperlipidemia |
Also Published As
Publication number | Publication date |
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FI982291A (en) | 2000-04-24 |
JP2002528571A (en) | 2002-09-03 |
WO2000024785A1 (en) | 2000-05-04 |
CN1331703A (en) | 2002-01-16 |
FI982291A0 (en) | 1998-10-23 |
AU1048600A (en) | 2000-05-15 |
EP1144458A1 (en) | 2001-10-17 |
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