(19) & (11) EP 2 311 448 A1 (12) EUROPEAN PATENT APPLICATION (43) Date of publication: (51) Int Cl.: 20.04.2011 Bulletin 2011/16 A61K 31/197 (2006.01) A61P 1/00 (2006.01) (21) Application number: 10186192.0 (22) Date of filing: 24.12.2004 (84) Designated Contracting States: (72) Inventor: Hageman, Robert Johan Joseph AT BE BG CH CY CZ DE DK EE ES FI FR GB GR 6705 CT, Wageningen (NL) HU IE IS IT LI LT LU MC NL PL PT RO SE SI SK TR (74) Representative: Swinkels, Bart Willem (30) Priority: 24.12.2003 EP 03079190 Nederlandsch Octrooibureau J. W. Frisolaan 13 (62) Document number(s) of the earlier application(s) in 2517 JS Den Haag (NL) accordance with Art. 76 EPC: 08163489.1 / 2 002 830 Remarks: 04808826.4 / 1 699 447 This application was filed on 01-10-2010 as a divisional application to the application mentioned (71) Applicant: N.V. Nutricia under INID code 62. 2712 HM Zoetermeer (NL) (54) Compositions comprising pantothenic acidor derivatives thereof and their use for stimulating appetite (57) The present invention relates to the field of food compositions. In particular compositions comprising at least 15 En% protein and pantothenic acid, or equivalents thereof, are provided, which are suitable for stimulating appetite. 48 A1 4 11 11 3 EP 2 Printed by Jouve, 75001 PARIS (FR) 1 EP 2 311 448 A1 2 Description source but which is devoid of pantothenic acid, benefit from the administration of pantothenic acid in terms of Field of the invention incease in weight and of food intake. The authors con- cluded however that there was no relation between level [0001] The present invention relates to the field of food 5 of pantothenic acid and food intake and that pantothenic compositions and their use. In particular compositions acid does not have an influence on growth which is re- comprising pantothenic acid, or equivalents thereof, are lated to appetite. Moreover, no relation is made to a po- provided, which are suitable for stimulating appetite. tential beneficial effect in human patients that have a completely different taste perception and especially no Background of the invention 10 relation is made to human beings that suffer from terminal cancer, AIDS, COPD or other severe disorders. [0002] Pantothenic acid is a water- soluble vitamin, al- [0004] EP 0914111 relates to methods and nutritional so known as vitamin B5, which is a component of coen- compositions for the prevention and treatment of cachex- zyme A (CoA). Pantothenic acid is found in a large range ia and anorexia. In this document there is no suggestion of foods, such as fish, meat, eggs, milk products and15 of a beneficial effect of pantothenic acid to appetite, nor vegetables, as a result of which natural deficiency is very was indicated that the amount of saturated fatty acids, in rarely observed in humans. In the past studies have been particular myristic acid is of any relevance. carried out in which pantothenic acid deficiency has been [0005] DE 4304394 concerns preparations for enteral induced experimentally in humans by administration of feeding of oncologic patients to overcome problems re- a pantothenic acid deficient diet (e.g. Fry et al. 1976, J. 20 lated to weight loss. The preparations are characterised Nutr. Sci. Vitamology 22, 339-346) and/or a compound by a balanced composition of specific types of fats. Also like omega-methyl pantothenic acid which is known to preparations are disclosed that include calcium pantoth- exhibit an anti-pantothenic acid-like effect (see e.g. enate and pantothenic acid but no relation between the Hodges et al. 1959, J. Clin. Invest. 38, 1421-1425). level of pantothenic acid and stimulating appetite was Symptoms exhibited by the participants of such trials25 mentioned or suggested. were gastrointestinal complaints (nausea, vomiting, ab- [0006] Several documents such as DE 29916231, JP dominal cramps), irritability, restlessness, fatigue, apa- 5294833 and US 6322821 describe multivitamin compo- thy, malaise, headache, insomnia, numbness or tingling sitions including calcium pantothenate that are useful to of feet and hands, parasthesia, muscle cramps, stagger- treat amongst others loss of appetite in humans and ing gait, hypoglycaemia and increased sensitivity to in- 30 cows. Neither of these documents however disclose a sulin (see e.g. Hodges et al. 1958, J. Clin. Invest. 37, critical role for the level of pantothenic acid in the com- 1642-1657; Report "Expert Group on Vitamins and Min- positions. No recommended dietary allowance (RDA) for erals 2003" published by the Food Standards Agency, pantothenic acid intake has been set by the Food and AviationHouse, 125 Kingsway, LondonWC2B 6NH, UK). Nutrition Board of the Institute of Medicine (Eissenstat et In other studies, where humans were on a pantothenic 35 al. 1986, Am. J. Clin. Nutr. 44(6), 931-937). Instead, only acid free diet, no clinical signs of deficiency developed approximate adequate daily dietary intake values (AI) (Fry et al. 1976, J. Nutr. Sci. Vitminol. 22(4), 339-346. It have been described for different age or target groups, is concluded that none of the above studies reveal that ranging from 1.7 mg/day in infants to 4-5 mg/day in adults pantothenic acid deficiency is related to the loss of ap- and 6-7 mg/day in pregnant or breastfeeding women (De- petite or that pantothenic acid can be used to restore40 partment of Health, 1991, In: Dietary reference values appetite loss. These studies neither reveal that pan- for food, energy and nutrients for the United Kingdom. tothenic acid can be used to restore bodyweight. It is HMSO, London, p113-115). Also, no tolerable upper lev- particularly noted that increased demands for pantothen- el for pantothenic acid has been set, as there seems to ic acid have never been associated with severe illnesses be no adverse effect of consumption of large amounts. such as cancer, AIDS, catabolism as a result of respira- 45 The only reported adverse effect described is the occur- tory diseases such as lung emphysema, severe traumata rence of diarrhea, associated with intake of 10-20 mg such as surgery and severe diarrhea such as for instance calcium D-pantothenate per day (Flodin 1988, Pharma- occurring with inflammatory bowel disease. In other cology of micronutrients; New York, Alan R. Liss, Inc.). words it is generally not believed that bad appetite and The UK Council for Responsible Nutrition has recom- weight loss associated with any severe illness is caused 50 mended an Upper Safe Level of pantothenic acid of 1000 by a pantothenic acid deficiency. mg/day for long and short term supplementation (leaflet [0003] Vaughan and Vaughan (J. Nutrition, (1960) 70: CRN 1999, The safe use of supplements benefit good 77-80) described the effect of cold on weight, food intake health). and acetylating acitivity of pantothenic acid deficient rats. [0007] Apart from dietary pantothenic acid uptake, They present some data from which it may derived that 55 bacteria colonising the colon are also able to produce healthy rats, that are brought in a pantothenic acid-defi- pantothenic acid, and it is therefore feasible that the pan- cient state by feeding for 33 days an artificial diet that tothenic acid produced in the subject’s intestine is ad- uses casein as protein source and vegetable oil as lipid sorbed and provides a further source of this vitamin (Said 2 3 EP 2 311 448 A1 4 et al. 1998, Am. J. Physiol. 275:C1365-1371). However, inclusion thereof is avoided in the state of the art. Instead it is not known whether internally produced pantothenate corn oil, rapeseed oil, sunflower or soybean oil are in- contributes in significant amounts to the body’s overall cluded which form homogeneous emulsions in complete pantothenate levels. In experimental set- ups, the internal formulae and comprise <0.5% myristic acid. These also bacterial production of pantothenic acid often necessi- 5 comprise high amounts of linoleic acid which is consid- tates treatment with antibiotics in order to elicit pan- ered highly desirable. tothenic acid deficiency in test animals (Stein and Dia- mond 1989, J. Nutr. 119(12), 1973-1983). Detailed description of the invention [0008] Commercially available vitamin supplements mostly also contain pantothenic acid, or derivatives10 Definitions thereof, such as calcium pantothenate, sodium pantoth- enate or panthenol, which are more stable than pan- [0012] "Pantothenic acid" or "pantothenate" or"vitamin tothenic acid. Mostly the D-isomer is used, although DL- B5" refers to a pantoic acid moiety amide linked to a beta- racemic mixtures may also be used. Pantothenate, which alanine subunit (pantoyl beta-alanine). This definition is is taken up with the diet, is adsorbed in the intestine and 15 limited to the active stereoisomer of pantothenate, name- transported via the blood (primarily as bound forms within ly the D- isomers of pantothenate. erythrocytes) to various body tissues. The majority of tis- [0013] "Pantothenic acid derivatives" or "pantothenic sues import pantothenic acid from the blood via an active acid equivalents" is used herein to refer to compounds sodium-dependent co-transport mechanism. Blood plas- derived from pantothenic acid and which have an equiv- ma levels of pantothenic acid have not been found to20 alent or improved appetite stimulating effect as that of correlate well with dietary intake levels, while a good cor- pantothenic acid, such as but not limited to: salts (e.g. relation between urinary excretion of pantothenate and calcium pantothenate, sodium pantothenate), esters or dietary intake has been found (Eissenstat et al. 1986, ethers of pantothenic acid; pantothenol (or panthenol, American J. of Clinical Nutrition 44, 931-937). pantothenyl alcohol); (R)-pantoate or its salts, esters or [0009] Dietary pantothenic acid supplements have25 ethers; pantetheine (pantothenic acid linked to a beta- been proposed to have a beneficial effect in the treatment mercaptoethylamine group) or its salts, esters or ethers, of obesity.