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WO2009108067A2 - Prévention et traitement de l’inflammation hsmi - Google Patents

Prévention et traitement de l’inflammation hsmi Download PDF

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Publication number
WO2009108067A2
WO2009108067A2 PCT/NO2009/000069 NO2009000069W WO2009108067A2 WO 2009108067 A2 WO2009108067 A2 WO 2009108067A2 NO 2009000069 W NO2009000069 W NO 2009000069W WO 2009108067 A2 WO2009108067 A2 WO 2009108067A2
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WO
WIPO (PCT)
Prior art keywords
group
atom
carbon atoms
oxygen atom
unsaturated
Prior art date
Application number
PCT/NO2009/000069
Other languages
English (en)
Other versions
WO2009108067A3 (fr
Inventor
Kjell-Arne RØRVIK
Henriette Alne
Magny Thomassen
Rolf Kristian Berge
Original Assignee
Thia Medica As
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 Thia Medica As filed Critical Thia Medica As
Priority to EP09714090A priority Critical patent/EP2257282A2/fr
Publication of WO2009108067A2 publication Critical patent/WO2009108067A2/fr
Publication of WO2009108067A3 publication Critical patent/WO2009108067A3/fr
Priority to NO20101223A priority patent/NO20101223L/no

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Classifications

    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/095Sulfur, selenium, or tellurium compounds, e.g. thiols
    • AHUMAN NECESSITIES
    • A23FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23KFODDER
    • A23K20/00Accessory food factors for animal feeding-stuffs
    • A23K20/10Organic substances
    • AHUMAN NECESSITIES
    • A23FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23KFODDER
    • A23K20/00Accessory food factors for animal feeding-stuffs
    • A23K20/10Organic substances
    • A23K20/158Fatty acids; Fats; Products containing oils or fats
    • AHUMAN NECESSITIES
    • A23FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23KFODDER
    • A23K40/00Shaping or working-up of animal feeding-stuffs
    • A23K40/30Shaping or working-up of animal feeding-stuffs by encapsulating; by coating
    • AHUMAN NECESSITIES
    • A23FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23KFODDER
    • A23K50/00Feeding-stuffs specially adapted for particular animals
    • A23K50/80Feeding-stuffs specially adapted for particular animals for aquatic animals, e.g. fish, crustaceans or molluscs
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/185Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
    • A61K31/19Carboxylic acids, e.g. valproic acid
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P21/00Drugs for disorders of the muscular or neuromuscular system
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P29/00Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/12Antivirals

Definitions

  • the present invention relates to the use of a compound for the preparation of a nutritional and/or pharmaceutical composition for the prevention and treatment of heart and skeletal muscle inflammation (HSMI). More specifically, the present invention relates to the reduced HSMI mortality, and to an improved growth during periods with HSMI challenges.
  • HSMI heart and skeletal muscle inflammation
  • HSMI Heart and skeletal muscle inflammation
  • Affected fish may become anorexic and display abnormal swimming, but may also be slow moving without any other external signs of disease.
  • HSMI is reported to cause histopathological lesions in heart and skeletal muscle.
  • the lesions associated with HSMI is partly similar to those described for two other serious diseases in modern salmon farming; pancreas disease (PD) and cardiomyopathy syndrome (CMS), making it difficult to distinguish between them.
  • PD pancreas disease
  • CMS cardiomyopathy syndrome
  • the main difference between HSMI and PD is the absence of pancreatic lesions in HSMI. The causes and metabolic mechanisms behind these diseases are not yet solved.
  • a first aspect of the present invention thus relates to the use of a compound represented by;
  • R"-COO-(CH2)2n+i-X-R ⁇ wherein X is a sulphur atom, a selenium atom, an oxygen atom, a SO group or a SO 2 group; wherein n is an integer of 0 to 11 ; and R' is a linear or branched alkyl group, saturated or unsaturated, optionally substituted, wherein the main chain of said R' contains from 13 to 23 carbon atoms and optionally one or more heterogroups selected from the group comprising an oxygen atom, a sulphur atom, a selenium atom, an oxygen atom, a SO group and a SO 2 group; and R" is a hydrogen atom or an alkyl group containing from 1 to 4 carbon atoms;
  • R1 , R2, and R3 represent i) a hydrogen atom; or ii) a group having the formula CO-R in which R is a linear or branched alkyl group, saturated or unsaturated, optionally substituted, and the main chain of said R contains from 1 to 25 carbon atoms; or iii) a group having the formula CO-(CH 2 WrX-R', wherein X is a sulphur atom, a selenium atom, an oxygen atom, a SO group or a SO 2 group; n is an integer of 0 to 11 ; and R' is a linear or branched alkyl group, saturated or unsaturated, optionally substituted, wherein the main chain of said R' contains from 13 to 23 carbon atoms and optionally one or more heterogroups selected from the group comprising an oxygen atom, a sulphur atom, a selenium atom, an oxygen atom, a CH 2 group, a SO group and a SO 2
  • A1 , A2 and A3 are chosen independently and represent an oxygen atom, a sulphur atom or an N-R4 group in which R4 is a hydrogen atom or a linear or branched alkyl group, saturated or unsaturated, optionally substituted, containing from 1 to 5 carbon atoms; wherein R1 , R2, and R3 represent i) a hydrogen atom or a linear or branched alkyl group, saturated or unsaturated, optionally substituted, containing from 1 to 23 carbon atoms; or ii) a group having the formula CO-R in which R is a linear or branched alkyl group, saturated or unsaturated, optionally substituted, and the main chain of said R contains from 1 to 25 carbon atoms; or iii) a group having the formula CO-(CH 2 WrX-R', wherein X is a sulphur atom, a selenium atom, an oxygen atom, a SO group or a SO 2 group
  • HSMI heart and skeletal muscle inflammation
  • a preferred embodiement relates to the use of the compounds defined in claim 1 for improving the cardiosomatic index (CSI) of fish with HSMI or which are susceptible for HSMI.
  • CSI cardiosomatic index
  • a further aspect of the invention relates to a compound represented by;
  • R"-COO-(CH 2 ) 2n +i-X-R ⁇ wherein X is a sulphur atom, a selenium atom, an oxygen atom, a SO group or a SO 2 group; wherein n is an integer of 0 to 11 ; and R' is a linear or branched alkyl group, saturated or unsaturated, optionally substituted, wherein the main chain of said R' contains from 13 to 23 carbon atoms and optionally one or more heterogroups selected from the group comprising an oxygen atom, a sulphur atom, a selenium atom, an oxygen atom, a SO group and a SO 2 group; and R" is a hydrogen atom or an alkyl group containing from 1 to 4 carbon atoms;
  • R1 , R2, and R3 represent i) a hydrogen atom; or ii) a group having the formula CO-R in which R is a linear or branched alkyl group, saturated or unsaturated, optionally substituted, and the main chain of said R contains from 1 to 25 carbon atoms; or iii) a group having the formula CO-(CH 2 WrX-R', wherein X is a sulphur atom, a selenium atom, an oxygen atom, a SO group or a SO 2 group; n is an integer of 0 to 11 ; and R' is a linear or branched alkyl group, saturated or unsaturated, optionally substituted, wherein the main chain of said R' contains from 13 to 23 carbon atoms and optionally one or more heterogroups selected from the group comprising an oxygen atom, a sulphur atom, a selenium atom, an oxygen atom, a CH 2 group, a SO group and a SO 2
  • A1 , A2 and A3 are chosen independently and represent an oxygen atom, a sulphur atom or an N-R4 group in which R4 is a hydrogen atom or a linear or branched alkyl group, saturated or unsaturated, optionally substituted, containing from 1 to 5 carbon atoms; wherein R1 , R2, and R3 represent i) a hydrogen atom or a linear or branched alkyl group, saturated or unsaturated, optionally substituted, containing from 1 to 23 carbon atoms; or ii) a group having the formula CO-R in which R is a linear or branched alky!
  • R contains from 1 to 25 carbon atoms; or iii) a group having the formula CO-(CH 2 WrX-R', wherein X is a sulphur atom, a selenium atom, an oxygen atom, a SO group or a SO 2 group; n is an integer of 0 to 11 ; and R' is a linear or branched alkyl group, saturated or unsaturated, optionally substituted, wherein the main chain of said R' contains from 13 to 23 carbon atoms and optionally one or more heterogroups selected from the group comprising an oxygen atom, a sulphur atom, a selenium atom, an oxygen atom, a CH2 group, a SO group and a SO 2 group; iv) an entity selected from the group comprising -PO 3 CH 2 CHNH 3 COOH (serine), PO 3 CH 2 CH 2 NH 3 (ethanolamine), PO 3 CH 2 CH 2
  • a nutritional or pharmaceutical composition for the manufacturing of a nutritional or pharmaceutical composition, for increasing the body weight of fish with HSMI or which are susceptible for HSMI.
  • composition is administered orally.
  • composition is fed to fish, such as tilapia, Atlantic cod, Atlantic halibut, European sea bass and salmonides, preferable Atlantic salmon or rainbow trout.
  • fish such as tilapia, Atlantic cod, Atlantic halibut, European sea bass and salmonides, preferable Atlantic salmon or rainbow trout.
  • the composition is administered or fed to the fish for a period of 12 weeks, preferable 6 weeks, more preferable 3 weeks or less.
  • Preferred compounds of the present invention are non ⁇ -oxidizable fatty acid such as tetradecylthioacetic acid (TTA), tetradecylselenoacetic acid and 3-Thia-15- heptadecyne.
  • TTA tetradecylthioacetic acid
  • tetradecylselenoacetic acid 3-Thia-15- heptadecyne
  • Further preferred compounds are modified phospholipids or mono-, di- or tri- acylglycerides.
  • the composition comprises an amount of a compound defined by (a)-(c) in the range of about 0.05% to 1 ,25%, related to the weight of the feed, or more preferable 0.1 % to 0.50%, related to the weight of the feed, and more preferable about 0,25%, related to the weight of the feed.
  • compositions comprising an amount of a compound defined by an amount of a compound defined by (a)-(c) in the range of about 0.05% to 0,5%, related to the weight of the total biomass, or more preferable 0.1 % to 0.25%, related to the weight of the total biomass.
  • a further aspect of the invention relates to a fish feed containing the compounds defined in claim 1 for the prevention or treatment of heart and skeletal muscle inflammation (HSMI) of fish, and/or for reducing the mortality of fish with HSMI or which are susceptible for HSMI, and/or for increasing the body weight of fish with HSMI or which are susceptible for HSMI.
  • HSMI heart and skeletal muscle inflammation
  • a preferred embodiment of said fish feed comprises an amount of a compound defined by an amount of a compound defined by (a)-(c) in the range of about 0.05% to 0,5%, related to the weight of the total biomass, or more preferable 0.1% to 0.25%, related to the weight of the total biomass, such a about 0,25%, or more preferable about 0,50%, related to the weight of the total biomass.
  • Another preferred embodiment of said fish feed comprises an amount of a compound defined by (a)-(c) in the range of about 0.05% to 1 ,25%, related to the weight of the feed, or more preferable 0.1 % to 0.50%, related to the weight of the feed, or more preferable about 0,25%, and more preferable about 0,50% of the weight of the feed.
  • TTA tetradecylthioacetic acid
  • the compounds of the present invention are blocked in various positions and cannot be beta-oxidized. Without being bound by theory, we believe that this inhibited ⁇ -oxidation will lead to an accumulation of fatty acids in the cell, and this accumulated amount will function as a positive feedback mechanism to increase the ⁇ -oxidation of normal fatty acids.
  • Figure 1 shows the cumulative mortality during a natural outbreak of HSMI from end of May until 20 th July 2007 for farmed 0+ Atlantic salmon given four different diets, either a low-fat control diet (C1 ), high-fat control diet (C2), C2 added 0.25% TTA (E1 ) or E1 added 0.2% Carnitine (E2).
  • Figure 2 shows the total mortality during a natural HSMI outbreak in spring for the control group or the experimental group of farmed 0+ Atlantic salmon. Significant differences between dietary groups are indicated by different letters on the bars.
  • FIG. 3 shows the changes in thermal growth coefficient (TGC) and feed conversion ratio (FCR) for 0+ salmon fed the control diets or experimental diets, throughout the experimental period.
  • the four different diets were: a commercial basic diet (C1-CPK 200), C1 coated with 3% fat (2% rapeseed oil and 1 % capelin oil) (C2), C2 added 0.25% TTA (E1 ) and E1 added 0.2% carnitine (E2).
  • C1-CPK 200 C1 coated with 3% fat (2% rapeseed oil and 1 % capelin oil)
  • E1 0.25% TTA
  • E1 E1 added 0.2% carnitine
  • the experimental diets were prepared by coating the basic diet in a blender. Carnitine was dissolved in distilled water and coated onto the surface of the feed pellets for E2, to a final inclusion of 0.2%. The similar amount of water was coated onto the two other high-dietary fat diets (C2 and E1 ) and all three diets were dried at room temperature.
  • C2 was then coated with 2% rapeseed oil and E1 and E2 were coated with TTA dissolved in the same amount of rapeseed oil, to make a final dietary level of 0.25%.
  • 1 % of capelin oil was coated onto the three diets. From week seven onwards (period 2), the fish were fed the same diet as in feeding period 1 , but without added TTA. In period 2, the commercial basic diet was adjusted to a bigger fish size in accordance to the manufacturer's guidelines and the pellet size was increased (CPK 500). The two basic diets were produced by Biomar AS (Norway) (Table 1 ). All the diets were fed in excess in duplicated net pens, and feed waste sampling was performed during both feeding periods.
  • Feed conversion ratio (FCR) was calculated as (kg feed fed) x (kg final biomass-kg initial biomass + kg dead fish) "1 .
  • Cardiosomatic index (CSI) was calculated as heart weight (g) x (body weight (g)) '1 x 100.
  • Relative percent survival (RPS) was calculated as described by Ahmend (1981 ) 100% x (1 - (% mortality in the experimental group x (% mortality in the control group) "1 )).
  • TTA diets resulted in a higher final body weight (1606 ⁇ 29 grams) than control diets (1580 ⁇ 31 grams).
  • FCR feed conversion ratio
  • the mortality started at different times in the net pens, and the mortality was highest at one side of the pier. This may indicate that the disease was spread among cages and also that the cages experienced different infectious pressure during the outbreak.
  • a block design was used in our experiment, making us able to observe dietary effects even though the mortality was higher at some positions.
  • Our study was not designed to differentiate and measure infectious pressure, but the results support the suggestions made that HSMI is contagious and spread in a cage to cage pattern (Kongtorp et al., 2004a, b).
  • the heart index was found to be higher in fish fed the TTA-supplemented diets compared to the control.

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
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  • Veterinary Medicine (AREA)
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  • Engineering & Computer Science (AREA)
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  • General Chemical & Material Sciences (AREA)
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  • Epidemiology (AREA)
  • Communicable Diseases (AREA)
  • Oncology (AREA)
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Abstract

L'invention concerne l’utilisation d’un composé dans la préparation d’une composition nutritionnelle et/ou pharmaceutique destinée à réduire la mortalité associée à l’inflammation HSMI (inflammation du cœur et des muscles squelettiques) chez le poisson.
PCT/NO2009/000069 2008-02-27 2009-02-27 Prévention et traitement de l’inflammation hsmi WO2009108067A2 (fr)

Priority Applications (2)

Application Number Priority Date Filing Date Title
EP09714090A EP2257282A2 (fr) 2008-02-27 2009-02-27 Prévention et traitement de l inflammation hsmi
NO20101223A NO20101223L (no) 2008-02-27 2010-09-02 Prevention and treatment of HSMI

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
NO20081040A NO20081040L (no) 2008-02-27 2008-02-27 Reduced HSMI mortality
NO20081040 2008-02-27

Publications (2)

Publication Number Publication Date
WO2009108067A2 true WO2009108067A2 (fr) 2009-09-03
WO2009108067A3 WO2009108067A3 (fr) 2009-11-12

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PCT/NO2009/000069 WO2009108067A2 (fr) 2008-02-27 2009-02-27 Prévention et traitement de l’inflammation hsmi

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EP (1) EP2257282A2 (fr)
CL (1) CL2009000460A1 (fr)
NO (2) NO20081040L (fr)
WO (1) WO2009108067A2 (fr)

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2011031166A3 (fr) * 2009-09-14 2011-07-28 Ewos Innovation As Composition d'aliment
WO2014070020A1 (fr) * 2012-11-01 2014-05-08 Ewos Innovation As Composition d'aliment pour les poissons

Family Cites Families (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CA2570050C (fr) * 2004-06-11 2013-03-05 Pharmaq As Virus (hsmi) d'inflammation musculaire squelettique et cardiaque
JP2008506773A (ja) * 2004-07-19 2008-03-06 ティア メディカ アクスイェ セルスカプ タンパク質材料と非酸化性脂肪酸体を含む組成物
NO20055541L (no) * 2005-11-23 2007-05-24 Berge Biomed As Use of fatty acid analogues

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2011031166A3 (fr) * 2009-09-14 2011-07-28 Ewos Innovation As Composition d'aliment
WO2014070020A1 (fr) * 2012-11-01 2014-05-08 Ewos Innovation As Composition d'aliment pour les poissons

Also Published As

Publication number Publication date
NO20081040L (no) 2009-08-28
WO2009108067A3 (fr) 2009-11-12
CL2009000460A1 (es) 2010-02-05
EP2257282A2 (fr) 2010-12-08
NO20101223L (no) 2010-09-02

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