WO2019098823A1

WO2019098823A1 - Composition comprising a2 b-casein and a vegetable fat mixture

Info

Publication number: WO2019098823A1
Application number: PCT/NL2018/050737
Authority: WO
Inventors: Randolph HAPPE; Alfred Jacques Haandrikman
Original assignee: Ausnutria Hyproca B.V.
Priority date: 2017-11-14
Filing date: 2018-11-02
Publication date: 2019-05-23
Also published as: CN111885928A; EP3709825A1; AU2018370363A1; WO2019098823A8; NL2019906B1

Abstract

Present invention relates to a composition comprising A2 β-casein and a fat mixture. The present invention further relates to the use of this composition for the treatment of gastrointestinal disorders. The composition of present invention can be used, for example as a dry powder or a liquid, in the production of dairy products for nutrition for infants and young children, such as infant formulas or clinical nutrition.

Description

COMPOSITION COMPRISING A2 B-CASEIN AND A VEGETABLE FAT MIXTURE

Present invention relates to a composition comprising A2 b-casein and a fat mixture. The present invention further relates to the use of this composition for the treatment of gastrointestinal disorders. The composition of present invention can be used, for example as a dry powder or a liquid, in the production of dairy products for nutrition for infants and young children, such as infant formulas or clinical nutrition.

Milk is the primary source of nutrition for infant mammals before they are able to digest other types of food. Regular milk and milk products have become part of our nutritional diet for centuries having over 6 billion consumers worldwide. However, the health effects of milk depend on the type of milk product being consumed and the breed of animal (e.g. bovine or goat) that produces the product.

Milk is an emulsion that is comprised of fat globules within a water-based fluid that contains dissolved carbohydrates and protein aggregates with minerals. These fat globules are composed of triacylglycerols and surrounded by a membrane phospholipids and proteins.

Furthermore, within the milk fat portion of the milk vitamins such as vitamin A, D, E, and K are found together with fatty acids such as linoleic and linolenic acid. Milk contains several different carbohydrate including lactose, glucose, galactose, and other oligosaccharides.

Regular bovine milk contains about 3.5 wt% of total protein, of which casein represents the largest group of proteins in milk, making up about 80% of the total protein content. There are four different types of casein proteins in milk, asl-, as2-, b-, and k-caseins. b-casein exists in at least 13 different forms of which the two most common forms of b-casein are A1 b- casein and A2 b-casein.

A1 and A2 milk contain different types of the b-casein protein. Regular bovine milk contains both A1 and A2 b-casein, whereas A2 milk consists mainly of variant of A2 b- casein, but not of A1 b-casein. A2 milk comprises b-casein, wherein all isoforms that have a point mutation at amino acid position 67 from histidine (H) to proline (P), including but not limited to the A2-, A3-, D-, E-, I- H2- isoforms of b-casein. It is thought that A1 b-casein is responsible for allergy, lactose intolerance, gut inflammation and discomfort. This is believed to be caused by a peptide known as beta-casomorphin-7 (BCM7) that is digested in the gut/stomach from A1 b - casein protein, but not from the A2 b -casein. For instance it has been shown that goat or camel milk, which lacks or contains less of the A1 b-casein as compared to regular bovine milk, is less allergenic. BCM-7 is not only released from regular milk, but also from other dairy products such as yoghurt and cheese.

It is believed that so called“A2 milk” is healthier than regular milk and is claimed to have several health benefits. A2 milk is believed to have beneficial effects on type I diabetes, coronary heart disease, schizophrenia, autism and lactose intolerance. Although a definite cause and effect relationship is not established instead of A2 milk, alternative milks could be used, e.g. goat or camel milk that in most cases contains low levels of A1 casein, but not necessarily, or soy milk. How'ever in the latter case it is known that also soy proteins are regarded as being allergens.

Furthermore, present milk product and infant formulas often lead to digestibility problems and feelings of discomfort. Currently, one of the solutions to reduce discomfort in for example infants, or to reduce the problems (in being allergic) that relate to the digestibility of the milk product is to provide a formula on basis of hydrolysed milk proteins. However, hydrolysed w'hey products have the disadvantage of having a distinct bitter taste and make them less suitable for use in infant formula, lnfant fed on formulas containing (extensively) hydrolysed proteins, often encounter serious issues later in life: difficulties with eating, very picky on certain foods/tastes etc. Furthermore, the use of extensively hydrolysed proteins in milk products such as infant formula are also less desirable, because their use substantially increases the osmotic pressure in the intestine thereby could increase the chance of osmotic diarrhoea.

Considering the above, there is a need in the art for milk products with improved digestibility and lead to a reduction of discomfort after consumption. Furthermore, there is a need in the art for milk product that leads to a reduced allergenic reaction or improved immune response.

lt is an object of the present invention, amongst other objects, to address the above need in the art. The object of present invention, amongst other objects, is met by the present invention as outlined in the appended claims.

Specifically, the above object, amongst other objects, is met, according to a first aspect, by the present invention by a composition comprising A2 b-casein and a fat mixture, wherein said fat mixture comprises triglycerides and wherein said triglycerides comprise saturated fatty acid residues. The known products in respect to either A2 b-casein or triglycerides, or ingredients for infant nutrition in general, focus on the alleviation of one adverse effect of the specific component. The compound of present invention combines the A2 b-casein and triglycerides to obtain a synergistic effect on the improved digestibility and reduced discomfort after consumption of the food product, for example a milk product comprising the composition of present invention.

Palmitic acid, also known as hexadecanoic acid (C HC_jCOOH) and stearic acid (C₁₇H₃₅COOH) are the most common saturated fatty acids found in animals, plants and microorganisms. Stearic acid is one of the most common saturated fatty acids found in nature following palmitic acid. In the triglycerides present in bovine milk, palmitic acid (C 16:0) and stearic acid (Cl 8:0) are evenly distributed between the sn-l / sn-3 (-35% and 10%) and sn-2 positions (~30% and 10%). The triglycerides present in human milk contains more palmitic acid (-60%) and less stearic acid (-5%) occupying the sn-2 position, in comparison to the amounts in the sn-1 and sn-3 positions (—16% and 15%, respectively).

According to a preferred embodiment, the present invention relates to the composition, wherein between 35 wt% to 80 wt%, preferably 40 wt% to 70 wt%, most preferably 45 wt% to 65 wt% of said saturated fatty acid residues are located at the sn-2 position of the triglycerides. The presence of saturated fatty acids at the sn-2 position of the triglyceride is preferred because it leads to intestinal health, healthy gut bacteria, softer stools, less crying, improved sleep, fat absorption, calcium uptake, and bone strength. On the other hand food products that encompass a fat phase in which the saturated fatty acids are predominantly attached to the sn-1 and sn-3 position, can cause several issues such as: the formation of insoluble soaps, constipation, cramps, longer crying episodes, short sleep cycles, reduced uptake of fatty acids, reduced uptake of minerals such as calcium and magnesium, hampered growth of the infant, and reduced bone mineral density and bone mineral concentration, hence therefore reduced bone strength.

According to another preferred embodiment, the present invention relates to the composition, wherein the saturated fatty acid residues that are located at the sn-2 position of the triglyceride have a chain length of between 8 to 26 carbon atoms, preferably between 10 to 24 carbon atoms, most preferably between 12 to 20 carbon atoms.

According to a preferred embodiment, the present invention relates to the composition, wherein the saturated fatty acid residues that are located at the sn-2 position of the triglyceride have a chain length of C16 or Cl 8, preferably C16. It was shown that fatty acid residues of 06 and Cl 8 in length lead to a significant reduced formation of calcium soaps during digestion of such triglycerides, and consequently results in less adverse effects i.e. discomfort after consumption.

According to a preferred embodiment, the present invention relates to the composition, wherein the triglycerides are comprised of at least one triglyceride selected from the group consisting of OXO, OXC, OXCa, OXLa, OXM, OXP, OXPa, OXL, OXLn, OXcL, OXG, OXS, OXA, OXE, OXD, XXL, XXLn, XXcL, XXG, XXS, XXA, XXE, XXD, XXX, CXC,

CXCa, CXLa, CXM, CaXCa, CaXLa, CaXM. LaXLa, LaXM, MXM, LXL, LXLn, LXcL, LXG, LnXLn, LnXcL, LnXG, cLXcL, cLXG. GXG, AXA, AXE, AXD, EXE, EXD and DXD, preferably OXO, most preferably OPO, wherein, X is a saturated fatty acid having a chain length of between 8 and 26 carbon atoms. C is caprylic acid, Ca is capric acid, La is lauric acid, M is myristic acid, P is palmitic acid, Pa is palmitoleic acid, S is stearic acid, O is oleic acid, L is linoleic acid, Ln is a-linolenic acid, cL is conjugated linoleic acid, G is gamma-linolenic acid, A is arachidonic acid, E is eicosapentaenoic acid and D is docosahexaenoic acid.

Preferably the composition of present invention comprises a combination of at least two triglycerides, in which the saturated fatly acids with a chain length of between 8 to 26 carbon atoms are primarily bound to the sn-2 position of the triglyceride molecule, selected from the group including OCO, OCaO, OLaO, OMO, OPO, OPaO, and OSO.

More preferably, the composition of present invention comprises at least one triglyceride having one or two unsaturated fatty acids with a chain length of 18 carbon atoms in the sn-1 and sn-3 position, selected from the group including linoleic acid, gamma-linolenic acid, alpha-linolenic acid and conjugated linoleic acid (cL), the latter including the cL-isomer cis-9, trans-11 conjugated linoleic acid.

Even more preferably, the composition of present invention comprises at least one triglyceride having one or two medium-chain fatty acids with a chain length of 8 to 12 carbon atoms in the sn-1 and sn-3 position, wherein the one or two medium-chain fatty acids are selected from the group consisting of caprylie acid, capric acid and laurie acid.

Most preferably, the composition of present invention comprises at least one triglyceride having long-chain poly-unsaturated fatty acids with a chain length of at least 20 carbon atoms in the sn-1 and sn-3 position, wherein the long-chain poly-unsaturated fatty acids are selected from the group consisting of arachidonic acid, eicosapentaenoic acid and doeosahexaenoic acid.

Several key benefits of human breast milk depend on a special fat/triglyceride structure, known as oleic-palmitic-oleic acid (OPO) fats. OPO fats are triglycerides that are especially enriched with palmitic acid in the middle, or sn-2, position of the triglycerides. OPO fats have been developed to mimic not only the fatty acid composition of human milk, they additionally have the intention to mimic the unique structure of the triglycerides in human milk. In human milk, the palmitic acid is found in a unique structure that is highly uncommon in other types of fat. This special OPO fat structure, known as sn-2 palmitate, has a very high proportion (70-75%) of palmitic acid bound to the second position (the middle or sn-2 position) of the triglyceride.

Therefore, OPO fat is also known as high 2-palmitic vegetable fat, b-Palmitate, or high sn-2 fat. The specific positioning of palmitic acid and other long-chain saturated fatty acids at the sn-2 position in human milk fat has been shown to enhance fat absorption and minimize calcium excretion. The OPO structure, as compared to a standard palm olein fat structure (POP instead of OPO), significantly reduces the formation of calcium soaps in the intestine during digestion. In addition to 1,3 dioleoyl 2 palmitoyl triglyceride (OPO), a variety of triglycerides are found in human milk, in which the long-chain saturated fatty acids are in the sn-2 position of the triglyceride, including OLaLa, MMLa, MLaM, LLaO, OMLa, OLaM, PMLa, MPLa, OLaO,

OMO, OPLa, OLaP, MPL. PML, SMM, MSM, MPLn, PMLn, OPL, OPLn, PPL, PPM, PMP, MPM, PPO, OPS, OSP, OSO. According to yet another preferred embodiment, the present invention relates to the composition, wherein said saturated fatty acid residues that are located at the sn-2 position are palmitic acid residues.

According to another preferred embodiment, the present invention relates to the composition, wherein the triglycerides are comprised of at least 10 wt%, more preferably at least 20 wt%, most preferably at least 40 wt% of 1,3-dioleoyl 2 -palmitic triglyceride, based on the total weight of the triglycerides present in the fat mixture.

According to a preferred embodiment, the present invention relates to the composition, wherein said A2 b-casein is present in the composition between 0.1 wt% and 15 wt%, preferably between 0.25 wt% and 12 wt%, most preferably between 0.5 and 10 wt%, based on the total weight of the composition. Within these ranges a balanced nutritional composition is provided, especially when the composition is used in the application as dairy product for young infants. A composition comprised of A2 b-casein within the selected ranges as indicated above assures an optimal protein quality, as well as a nutritionally sound amino acid composition.

Furthermore, the composition provides a proper amount of protein, such that the change of malnutrition or overfeeding is being minimized.

Preferably the A2 b-casein in the composition of present invention is derived from mammalian milk, wherein the mammalian milk is from mammals that produce milk that is low' (at most 20 wt%) in A1 casein concentration. Mammalian milk include milk obtained from cow', goat, sheep, donkey, buffalo, camel, yak and equine.

According to another preferred embodiment, the present invention relates to the composition, w'herein the composition further comprises at most 20 wt% of A1 B-casein, preferably at most 10 wt%, more preferably at most 1 wt%, based on the total w'eight of the composition. In the composition of present invention the A1 B-casein is preferably as low as possible, preferably absent from the composition.

According to yet another preferred embodiment, the present invention relates to the composition, wherein said composition has a total protein content of between 5 wt% and 40 wt%, preferably between 7.5 wt% and 30 wt%, based on the total weight of the composition.

According to a preferred embodiment, the present invention relates to the composition, w'herein said composition has a total fat content of betw'een 10 wt% to 40 wt%, preferably between 15 wt% to 30 wt%, based on the total weight of the composition, and w'herein at least 35 wt%, preferably at least 45 wt%, most preferably at least 55 wt% of said total fat content is comprised of the oleic-palmitic-oleic acid (OPO) fat.

According to yet another preferred embodiment, the present invention relates to the composition, wherein said fat mixture further comprises cow milk fat, w'herein said cow milk fat comprises between 2 wt% to 70 wt%, preferably 15 wt% to 65 wt%, more preferably 20 wt% to 60 wt%, based on the total fat content of the fat mixture.

According to another preferred embodiment, the present invention relates to the composition, wherein said composition further comprises at most 0.05 wt% lactose. For example the composition may be free from lactose. For example a dairy product that comprises the composition of present invention can be an A2 OPO milk infant formula which is free from lactose. Furthermore the composition of present invention may comprise a lactose in the concentration of at most 2.5 mg/100 kJ or at most 0.05 wt%. Such products product would decrease issues in respect to digestibility and lead to a reduction of discomfort after consumption as found with the present infant formulas and makes it fully suited for lactose intolerant infants.

According to yet another preferred embodiment, the present invention relates to the composition, wherein said composition further comprises hydrolysed whey protein. When combining the composition of present invention further with hydrolysed whey protein, digestion of a food product comprising this composition will be further improved by formation of an even softer curd during gastric digestion, improving the comfort during consummation.

The present invention, according to a second aspect, relates to the composition for use in the treatment of a gastrointestinal disorder. The gastrointestinal disorder is selected from the group consisting of lactose intolerance, diarrhoea, osmotic diarrhoea, inflammatory bowel disease, gastrointestinal leakage, irritable bowel syndrome, constipation, and reflux. Furthermore, the composition of present invention can improve bone health, nutrient absorption, boosts the immune response, supports brain development, enhances cognitive function, is easy to digest and improves the balance of the intestinal microflora (i.e. improved colonization of beneficial gut microbiota, healthy gut microbiota composition). The intestinal microflora serves numerous important functions, including protection against pathogens and modulation of inflammatory and immune responses.

The present invention, according to a further aspect, relates to the composition for use in the treatment of brain disorders or enhancement of brain function.

The present invention, according to a further aspect, relates to the composition for use in the treatment of bone disorders.

The present invention, according to a further aspect, relates to the composition for use in a food composition or dairy product. The food composition or dairy product is preferably a dry powder or a liquid, wherein the dairy product is selected from the group consisting of an infant formula, follow-on formula, growing-up milk, formulas for pre-term infants and low-birthweight term infants, maternal nutrition, elderly nutrition, sports- and performance nutrition, recovery nutrition, and clinical nutrition, preferably an infant formula. The food composition or dairy products are mainly intended for nutrition for infants and young children and may include infant formulas for term infants (0-6 months), follow- on formulas (6-12 months), growing-up milk (1-3 years), specialty formulas for (low-birthweight) pre-term infant, specialty formulas for infants and children suffering from lactose intolerance (lactose-free) and specialty formulas for digestive health. Additional products could be envisaged for groups of consumers with specific needs, not limited to performance nutrition for amateur and professional athletes, maternal nutrition, elderly nutrition, and clinical nutrition. Such products are commonly available as instant powder, to be dissolved in warm water prior to consumption. For example, a liquid milk formula based on the composition of present invention can be obtained by dissolving of dry powder of the composition in water. The food composition or dairy product can also be a ready-to-feed liquid formulation, packed in an aseptic packaging, such as an aseptic pouch or aseptic bottle. As alternative, sterilized, ready -to-drink formula (sold as liquid) is another possible dairy product format.

Claims

1. Composition comprising A2 b-casein and a fat mixture, wherein said fat mixture comprises triglycerides and wherein said triglycerides comprise saturated fatty acid residues.

2. Composition according to claim 1, wherein between 35 wt% to 80 wt%, preferably 40 wt% to 70 wt%, most preferably 45 wt% to 65 wt% of said saturated fatty acid residues are located at the sn-2 position of the triglycerides.

3. Composition according to claim 1 or 2, wherein the saturated fatly acid residues that are located at the sn-2 position of the triglyceride have a chain length of between 8 to 26 carbon atoms, preferably between 10 to 24 carbon atoms, most preferably between 12 to 20 carbon atoms.

4. Composition according to any of the claims 1 to 3, wherein the saturated fatty acid residues that are located at the sn-2 position of the triglyceride have a chain length of C16 or Cl 8. preferably Cl 6.

5. Composition according to any of the claims 1 to 4, wherein the triglycerides are comprised of at least one triglyceride selected from the group consisting of OXO, OXC, OXCa, OXLa, OXM, OXP, OXPa, OXL, OXLn, OXcL. OXG, OXS, OXA. OXE, OXD, XXL, XXLn. XXcL, XXG, XXS, XXA, XXE, XXD, XXX, CXC, CXCa, CXLa, CXM, CaXCa, CaXLa, CaXM, LaXLa, LaXM, MXM, LXL, LXLn, LXcL, LXG, LnXLn, LnXcL, LnXG, cLXcL, cLXG, GXG, AXA, AXE, AXD, EXE, EXD and DXD, preferably OXO, most preferably OPO, wherein,

X is a saturated fatty acid with a chain length of between 8 and 26 carbon atoms.

C is caprylic acid,

Ca is capric acid,

La is lauric acid,

M is myristic acid,

P is palmitic acid,

Pa is palmitoleic acid,

S is stearic acid,

O is oleic acid,

L is linoleic acid,

Ln is a-linolenic acid,

cL is conjugated linoleic acid, G is gamma-linolenic acid,

A is arachidonic acid,

E is eicosapentaenoic acid, and

D is docosahexaenoic acid.

6. Composition according to any of the claims 1 to 5, wherein said saturated fatly acid residues that are located at the sn-2 position are palmitic acid residues.

7. Composition according to any of the claims 1 to 6, wherein said triglycerides are comprised of at least 10 wt%, more preferably at least 20 wt%, most preferably at least 40 wt% of

1 ,3-dioleoyl 2 -palmitic triglyceride, based on the total weight of the triglycerides present in the fat mixture.

8. Composition according to any of the claims 1 to 7, wherein said A2 b-casein is present in the composition between 0.1 wt% and 15 wt%, preferably between 0.25 wt% and 12 wt%, most preferably between 0.5 and 10 wt%, based on the total weight of the composition.

9. Composition according to any of the claims 1 to 8, wherein said composition further comprises at most 20 wt% of A1 B-casein, preferably at most 10 wt%, more preferably at most 1 wt%, based on the total weight of the composition.

10. Composition according to any of the claims 1 to 9, wherein said composition has a total protein content of between 5 wt% and 40 wt%, preferably between 7.5 wt% and 30 wt%, based on the total weight of the composition.

11. Composition according to any of the claims 1 to 10, wherein said composition has a total fat content of between 10 wt% to 40 wt%, preferably between 15 wt% to 30 wt%, based on the total weight of the composition, and wherein at least 35 wt%, preferably at least 45 wt%, most preferably at least 55 wt% of said total fat content is comprised of oleic-palmitic-oleic acid (OPO) fat.

12. Composition according to any of the claims 1 to 11, wherein said fat mixture further comprises cow milk fat, wherein said cow milk fat comprises between 2 wt% to 70 wt%, preferably 15 wt% to 65 wt%, more preferably 20 wt% to 60 wt%, based on the total fat content of the fat mixture.

13. Composition according to any of the claims 1 to 12,, wherein said composition further comprises at most 0.05 wt% lactose.

14. composition according to any of the claims 1 to 13, wherein said composition further comprises hydrolysed whey protein.

15. Composition according to any of the claims 1 to 14 for use in the treatment of a gastrointestinal disorder.

16. Composition for use according to claim 15, wherein said gastrointestinal disorder is selected from the group consisting of lactose intolerance, diarrhoea, osmotic diarrhoea, inflammatory bowel disease, gastrointestinal leakage, irritable bowel syndrome, constipation, and reflux.

17. Composition according to any of the claims 1 to 14 for use in treatment of brain disorders or enhancement of brain function.

18. Composition according to any of the claims 1 to 14 for use in the treatment of bone disorders.

19. Composition according to any one of the claims 1 to 14 for use in a food composition or dairy product.

20. Composition according to claim 19, wherein the food composition or dairy product is a dry powder or a liquid, wherein the product is selected from the group consisting of an infant formula, follow-on formula, growing-up milk, formulas for pre-term infants and low- birlhweight term infants, maternal nutrition, elderly nutrition, sports- and performance nutrition, recovery nutrition, and clinical nutrition, preferably an infant formula.