WO2018052357A1 - A dietary supplement for alleviating chronic inflammation in colon - Google Patents
A dietary supplement for alleviating chronic inflammation in colon Download PDFInfo
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- WO2018052357A1 WO2018052357A1 PCT/SE2017/050789 SE2017050789W WO2018052357A1 WO 2018052357 A1 WO2018052357 A1 WO 2018052357A1 SE 2017050789 W SE2017050789 W SE 2017050789W WO 2018052357 A1 WO2018052357 A1 WO 2018052357A1
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- ester composition
- glycerol ester
- glyceryl
- composition according
- weight
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- 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
- A61K31/21—Esters, e.g. nitroglycerine, selenocyanates
- A61K31/215—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids
- A61K31/22—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids of acyclic acids, e.g. pravastatin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
-
- 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
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
Definitions
- the present invention refers to a glycerol ester composition comprising glyceryl valerate for alleviating chronic inflammation in colon.
- the high fat diets of the western world has become a growing problem since several decades. It is part of human nature to eat while food is available and also to prefer food with high energy content. This is a genetically inherited disposition that has served civilization well since before civilization during times when food supply was highly seasonal and sometimes scarce. A body fat depot would then allow us to survive times of famine. In modern time, with all types of food being available out of season and in abundance, at least in the western world, our genetic disposition will become a burden. A majority of us will still select food with high energy value as if we were expecting times of starvation.
- High fat diets are believed to be a direct factor behind certain health disorders, in some other it is considered a contributing factor.
- high fat diets are known to cause dysbiosis, i.e. an imbalance of the microbiota composition in colon and in the gut metabolites formed, such as short-chain fatty acids.
- dysbiosis i.e. an imbalance of the microbiota composition in colon and in the gut metabolites formed, such as short-chain fatty acids.
- a dysbiotic microbiota is believed to be the underlying cause to inflammatory diseases in colon (e.g. ulcerative colitis and in the long term colon cancer).
- Another factor that is discussed in this respect is the diminished capacity by the colon mucosa to utilize certain short-chain fatty acids such as butyric acid.
- Succinic acid has been shown to increase at intake of high fat diets and an imbalanced microbiota, at the expense of butyrate and could thus be an early marker for inflammation in colon.
- the present invention relates to a glycerol ester composition
- a glycerol ester composition comprising glyceryl valerate.
- the invention is characterized in that the composition is used for treating dysbiosis in the colon, said dysbiosis being caused by high fat diets, thereby alleviating long term sequela chronic inflammation comprising ulcerative colitis in the colon of human.
- the herein disclosed treatment for dysbiosis will reduce the long term sequela threat in the form of type 2 diabetes by at least 30% over a period of 25 years. According to another embodiment of the invention the herein disclosed treatment for dysbiosis will reduce the long term sequela threat in the form of colon cancer by at least 30% over a period of 30 years.
- the glyceryl valerate is glyceryl monovalerate.
- Said glyceryl monovalerate is suitably administered in the range 0.3 - 0.8 % by weight of the daily food ration for alleviating effects of chronic inflammation in the colon of a human.
- the glyceryl valerate is a glyceryl trivalerate.
- Said glyceryl trivalerate is suitably administered in the range 0.3 - 0.8 % by weight of the daily food ration for alleviating effects of low-grade inflammation in the colon of a human.
- the glyceryl valerate is mixture of glyceryl monovalerate and glyceryl trivalerate.
- Said glyceryl mono-/tri-valerate mixture is suitably administered in the range 0.3 - 0.8 % by weight of the daily food ration for alleviating effects of chronic inflammation in the colon of a human.
- an inflammatory marker in the form of succinic acid is suitably decreased by at least 30%.
- a glycerol ester composition in accordance with an embodiment of the invention is suitably achieved by reacting glycerol and valeric acid at a molar ratio of between 1 : 0.8 and 1 : 1.2 to form said glycerol ester.
- Said glycerol ester composition suitably comprises at least 30% by weight of glyceryl monovalerate, below 20% by weight of glyceryl divalerate and below 5% by weight of glyceryl trivalerate.
- Said glycerol ester composition preferably comprises at least 40% by weight of glyceryl monovalerate, below 15% by weight of glyceryl divalerate and below 2% by weight of glyceryl trivalerate.
- a glycerol ester composition in accordance with another embodiment of the invention is suitably achieved by reacting glycerol and valeric acid at a molar ratio of between 1 : 2.5 and 1 : 4 to form said glycerol ester.
- Said glycerol ester composition suitably comprises below 10% of glyceryl monovalerate and below 20% of glyceroldivalerate.
- the amount of free valeric acid in said glycerol ester composition is below 2 % by weight.
- the glycerol ester composition is suitably adsorbed on a carrier, such as a silica carrier, thereby allowing said glycerol ester composition to be distributed as a dry product.
- a carrier such as a silica carrier
- the claimed invention is particularly suited for treatment of a human consuming diets with high fat content.
- a group of male Wistar rats were randomly divided into three subgroups; group A, group B and group C.
- Group A, group B and group C were allowed a three day period of
- Group A control
- Group B and C tested groups
- the diets for group A - C where identical with the exception that group B and C where diets also contained glyceryl monovalerate and glyceryl trivalerate respectively.
- test groups where allowed free access to their respective diet above for a period of 21 days.
- test groups also had free access to water.
- the temperature during the test was 21 °C and a 12 hour day / 12 hour night cycle was applied.
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- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
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- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
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- Emergency Medicine (AREA)
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- Obesity (AREA)
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Abstract
The present invention relates to a glyceryl ester composition comprising glyceryl valerate, for treating dysbiosis in the colon, said dysbiosis being caused by high fat diets, thereby alleviating long term sequela chronic inflammation comprising ulcerative colitis in the colon of human. Furthermore, the present invention also relates to a composition wherein the long term sequela threat in the form of type 2 diabetes and/or colon cancer is reduced. Glyceryl monovalerate and glyceryl trivalerate are mentioned as preferred glyceryl valerates.
Description
A DIETARY SUPPLEMENT FOR ALLEVIATING CHRONIC INFLAMMATION IN COLON.
The present invention refers to a glycerol ester composition comprising glyceryl valerate for alleviating chronic inflammation in colon.
The high fat diets of the western world has become a growing problem since several decades. It is part of human nature to eat while food is available and also to prefer food with high energy content. This is a genetically inherited disposition that has served humanity well since before civilization during times when food supply was highly seasonal and sometimes scarce. A body fat depot would then allow us to survive times of famine. In modern time, with all types of food being available out of season and in abundance, at least in the western world, our genetic disposition will become a burden. A majority of us will still select food with high energy value as if we were expecting times of starvation.
High fat diets are believed to be a direct factor behind certain health disorders, in some other it is considered a contributing factor. Thus, high fat diets are known to cause dysbiosis, i.e. an imbalance of the microbiota composition in colon and in the gut metabolites formed, such as short-chain fatty acids. A dysbiotic microbiota is believed to be the underlying cause to inflammatory diseases in colon (e.g. ulcerative colitis and in the long term colon cancer). Another factor that is discussed in this respect is the diminished capacity by the colon mucosa to utilize certain short-chain fatty acids such as butyric acid. Succinic acid has been shown to increase at intake of high fat diets and an imbalanced microbiota, at the expense of butyrate and could thus be an early marker for inflammation in colon.
There are postulated theories that inflammatory diseases may be one of the factors behind insulin resistance and type 2 diabetes.
Accordingly the present invention relates to a glycerol ester composition comprising glyceryl valerate. The invention is characterized in that the composition is used for treating dysbiosis in the colon, said dysbiosis being caused by high fat diets, thereby alleviating long term sequela chronic inflammation comprising ulcerative colitis in the colon of human.
According to one embodiment of the invention the herein disclosed treatment for dysbiosis will reduce the long term sequela threat in the form of type 2 diabetes by at least 30% over a period of 25 years.
According to another embodiment of the invention the herein disclosed treatment for dysbiosis will reduce the long term sequela threat in the form of colon cancer by at least 30% over a period of 30 years.
According to one embodiment of the invention the glyceryl valerate is glyceryl monovalerate. Said glyceryl monovalerate is suitably administered in the range 0.3 - 0.8 % by weight of the daily food ration for alleviating effects of chronic inflammation in the colon of a human.
According to another embodiment of the invention the glyceryl valerate is a glyceryl trivalerate. Said glyceryl trivalerate is suitably administered in the range 0.3 - 0.8 % by weight of the daily food ration for alleviating effects of low-grade inflammation in the colon of a human.
According to one alternative embodiment of the invention the glyceryl valerate is mixture of glyceryl monovalerate and glyceryl trivalerate. Said glyceryl mono-/tri-valerate mixture is suitably administered in the range 0.3 - 0.8 % by weight of the daily food ration for alleviating effects of chronic inflammation in the colon of a human.
According to the invention an inflammatory marker in the form of succinic acid is suitably decreased by at least 30%.
A glycerol ester composition in accordance with an embodiment of the invention is suitably achieved by reacting glycerol and valeric acid at a molar ratio of between 1 : 0.8 and 1 : 1.2 to form said glycerol ester.
Said glycerol ester composition suitably comprises at least 30% by weight of glyceryl monovalerate, below 20% by weight of glyceryl divalerate and below 5% by weight of glyceryl trivalerate. Said glycerol ester composition preferably comprises at least 40% by weight of glyceryl monovalerate, below 15% by weight of glyceryl divalerate and below 2% by weight of glyceryl trivalerate.
A glycerol ester composition in accordance with another embodiment of the invention is suitably achieved by reacting glycerol and valeric acid at a molar ratio of between 1 : 2.5 and 1 : 4 to form said glycerol ester. Said glycerol ester composition suitably comprises below
10% of glyceryl monovalerate and below 20% of glyceroldivalerate.
According to one embodiment of the invention, the amount of free valeric acid in said glycerol ester composition is below 2 % by weight.
The glycerol ester composition is suitably adsorbed on a carrier, such as a silica carrier, thereby allowing said glycerol ester composition to be distributed as a dry product.
The phrase "alleviate" in this application is to be understood as that the chronic inflammation is significantly reduced and therefore that the long term effects of such chronic inflammation is also reduced. Among such long term effects that take many years or even several decades to develop as a sequela are type 2 diabetes and colon cancer. Succinic acid is an early marker of an imbalanced microbiota causing such chronic inflammation indicating that the natural and healthy microbial balance has been disturbed. Such an imbalance is believed to be the cause of many health disorders and may even be one of the factors in development of colonic cancer besides other known long term effects such as coronary heart diseases and atherosclerosis.
The claimed invention is particularly suited for treatment of a human consuming diets with high fat content.
A study was performed on rat who was fed a simulated high fat diet.
A group of male Wistar rats were randomly divided into three subgroups; group A, group B and group C. Group A, group B and group C were allowed a three day period of
acclimatization and were then given the test diet. Group A (control) were given free access to the test diet of table 1 column A while Group B and C (tested groups) were given free access to test diet of table 1 column B and C respectively. The diets for group A - C where identical with the exception that group B and C where diets also contained glyceryl monovalerate and glyceryl trivalerate respectively.
As said above, all test groups where allowed free access to their respective diet above for a period of 21 days. In addition the test groups also had free access to water. The temperature during the test was 21 °C and a 12 hour day / 12 hour night cycle was applied.
After the test period the rats were anaesthetised for tissue harvesting. From blood samples of the test subjects the levels of cholesterols were analysed and compared between the two test groups. See diagram A (succinic acid).
It is shown that the administered composition in accordance with the invention significantly lowered the levels of succinic acid.
Claims
1. A glycerol ester composition comprising glyceryl valerate, for treating dysbiosis in the colon, said dysbiosis being caused by high fat diets, thereby alleviating long term sequela chronic inflammation comprising ulcerative colitis in the colon of human.
2. A glycerol ester composition according to claim 1, wherein the long term sequela threat in the form of type 2 diabetes is reduced by at least 30% over e period of 25 years.
3. A glycerol ester composition according to claim 1, wherein the long term sequela threat in the form of colon cancer is reduced by at least 30% over a period of 30 years.
4. A glycerol ester composition according to claim 1, wherein the glyceryl valerate is glyceryl monovalerate.
5. A glycerol ester composition according to claim 1, wherein the glyceryl valerate is a glyceryl trivalerate.
6. A glycerol ester composition according to claim 4, wherein the glyceryl monovalerate is administered in the range 0.3 - 0.8 % by weight of the daily food ration for alleviating effects of chronic inflammation in the colon of a human.
7. A glycerol ester composition according to claim 5, wherein the glyceryl trivalerate is administered in the range 0.3 - 0.8 % by weight of the daily food ration for alleviating effects of chronic inflammation in the colon of a human.
8. A glycerol ester composition according to any of claims 1 - 7, wherein a chronic
inflammation marker in the form of succinic acid is decreased by at least 30%.
9. A glycerol ester composition according to claim 4, wherein said glycerol ester composition comprises the reaction product obtained from reacting glycerol and valeric acid at a molar ratio of between 1 : 0.8 and 1 : 1.2.
10. A glycerol ester composition according to claim 5, wherein said glycerol ester composition comprises the reaction product obtained from reacting glycerol and valeric acid at a molar ratio of between 1 : 2.5 and 1 : 4.
11. A glycerol ester composition according to claim 4, wherein said glycerol ester composition comprises at least 30% by weight of glyceryl monovalerate, below 20% by weight of glyceryl divalerate and below 5% by weight of glyceryl trivalerate.
12. A glycerol ester composition according to claim 11, wherein said glycerol ester composition comprises at least 40% by weight of glyceryl monovalerate, below 15% by weight of glyceryl divalerate and below 2% by weight of glyceryl trivalerate.
13. A glycerol ester composition according to claim 5, wherein said glycerol ester composition comprises below 10% of glyceryl monovalerate and below 20% of glyceroldivalerate.
14. A glycerol ester composition according to claim 4 or 5, wherein the amount of free valeric acid in said glycerol ester composition is below 2 % by weight.
15. A glycerol ester composition according to claim 4 or 5, wherein said glycerol ester composition is adsorbed on a carrier, such as a silica carrier, thereby allowing said glycerol ester composition to be distributed as a dry product.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| SE1630228 | 2016-09-19 | ||
| SE1630228-3 | 2016-09-19 |
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| Publication Number | Publication Date |
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| WO2018052357A1 true WO2018052357A1 (en) | 2018-03-22 |
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| PCT/SE2017/050789 WO2018052357A1 (en) | 2016-09-19 | 2017-07-18 | A dietary supplement for alleviating chronic inflammation in colon |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP3373925A4 (en) * | 2015-11-13 | 2019-07-10 | Perstorp AB | Composition preventing bacterial inflammation in monogastric animals |
Citations (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5919822A (en) * | 1990-04-10 | 1999-07-06 | Baxter International, Inc. | Use of short chain fatty acid containing lipids to maintain gastrointestinal integrity and function in patients |
| US20020137780A1 (en) * | 1995-02-13 | 2002-09-26 | Wu Gary W. | Differentiating agents for the treatment of inflammatory intestinal diseases |
| EP1576962A1 (en) * | 1998-03-04 | 2005-09-21 | Nps Pharmaceuticals, Inc. | Composition comprising isovaleramide and ibuprofen |
| WO2011002298A2 (en) * | 2009-07-03 | 2011-01-06 | Nutreco Nederland B.V. | Animal feed or human food for improving intestinal barrier properties |
| WO2016093757A1 (en) * | 2014-12-09 | 2016-06-16 | Perstorp Ab | Composition inhibiting gram-negative pathogens in galloanserans |
| WO2016159853A1 (en) * | 2015-03-27 | 2016-10-06 | Perstorp Ab | Composition inhibiting gram-positive, pathogenic bacteria |
| WO2017082791A1 (en) * | 2015-11-13 | 2017-05-18 | Perstorp Ab | Composition preventing bacterial inflammation in monogastric animals |
-
2017
- 2017-07-18 WO PCT/SE2017/050789 patent/WO2018052357A1/en active Application Filing
Patent Citations (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5919822A (en) * | 1990-04-10 | 1999-07-06 | Baxter International, Inc. | Use of short chain fatty acid containing lipids to maintain gastrointestinal integrity and function in patients |
| US20020137780A1 (en) * | 1995-02-13 | 2002-09-26 | Wu Gary W. | Differentiating agents for the treatment of inflammatory intestinal diseases |
| EP1576962A1 (en) * | 1998-03-04 | 2005-09-21 | Nps Pharmaceuticals, Inc. | Composition comprising isovaleramide and ibuprofen |
| WO2011002298A2 (en) * | 2009-07-03 | 2011-01-06 | Nutreco Nederland B.V. | Animal feed or human food for improving intestinal barrier properties |
| WO2016093757A1 (en) * | 2014-12-09 | 2016-06-16 | Perstorp Ab | Composition inhibiting gram-negative pathogens in galloanserans |
| WO2016159853A1 (en) * | 2015-03-27 | 2016-10-06 | Perstorp Ab | Composition inhibiting gram-positive, pathogenic bacteria |
| WO2017082791A1 (en) * | 2015-11-13 | 2017-05-18 | Perstorp Ab | Composition preventing bacterial inflammation in monogastric animals |
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| Title |
|---|
| BLANDINO, G. ET AL.: "Impact of gut microbiota on diabetes mellitus", DIABETES & METABOLISM, vol. 42, 2016, pages 303 - 315, XP029786817 * |
| DEGRUTTOLA, A.K. ET AL.: "Current understanding of dysbiosis in disease in human and animal models", INFLAMMATORY BOWEL DISEASE, vol. 22, no. 5, 2016, pages 1137 - 1150 * |
| JOO-HUI, H. ET AL.: "The effects of propionate and valerate on insulin responsiveness for glucose uptake in 3T3-L1 adipocytes and C2C12 myotubes via G protein-coupled receptor 41", PLOS ONE, vol. 9, no. 4, 18 April 2014 (2014-04-18), pages 1 - 9, XP055499626 * |
| VAN DRIESSCHE, K. ET AL.: "Protective effects of glyceride derivatives of butyric and valeric acid on necrotic enteritis in poultry", 1ST INTERNATIONAL CONFERENCE ON NECROTIC ENTERITIS IN POULTRY, June 2015 (2015-06-01), Copenhagen, Denmark * |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP3373925A4 (en) * | 2015-11-13 | 2019-07-10 | Perstorp AB | Composition preventing bacterial inflammation in monogastric animals |
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