The present invention relates to an effervescent tablet comprising a high amount of at least one Human Milk Oligosaccharide (HMO).

The goal of the present invention was to find a way to provide a formulation comprising a high amount of at least one HMO.

There is a variety of formulation of dietary supplements.

A very common formation for dietary supplements are for examples tablets, pills, gummies or capsule forms. Pills and capsules are difficult for many people to swallow and/or digest. Manufacturing of such dietary supplements in pill/tablet form requires the use of fillers and/or binding agents in order to produce a tablet that is solid and has an acceptable shelf life. Manufactured tablets or capsules can be often large which tends to limit the amount of active ingredient content per delivery form and results in some efficacious dosages requiring multiple pills or tablets. Many consumers will avoid or are unable to take large pills, which leaves the consumer with few attractive alternatives.

So, it was found that when incorporating at least one HMO into an effervescent tablet it is possible to add a high amount thereof.

Effervescent tablets do have a variety of advantages over tablets and other formulations. Such advantages are for example:

• Better and quicker adsorption:

In water, soda, and fruit juices, effervescent tablets produce a pleasant tasting solution. This is due to organic fruit acids contained in the tablets. In conventional solid tablets, compounds dissolve slowly in the stomach, which frequently delays or reduces absorption. With effervescent tablets dissolved in a liquid, the ingredients are absorbed quickly, completely, and uniformly.

• Optimal compatibility:

After swallowing, conventional solid tablets or capsules are transported to the stomach where they dissolve gradually. The passage time varies in different people, depending on anatomical and physiological factors. In case of a longer passage time, solid dosage forms can dissolve partially, and this may cause irritation of mucous membranes. With a dissolved effervescent tablet, the ingredients are evenly distributed in the solution, so that high, localized concentrations cannot occur. The solution of the effervescent tablet contains a balanced ratio of acids and carbonates. This balance is called a buffer.

• Increase in liquid intake:

Daily liquid consumption should be 1.5- 2 litres in adults. Effervescent tablets provide both the nutritional value intended and additional liquid intake. And with increased intake required during excessive fluid loss caused by events such as intensive physical activity, diarrhea, or high temperatures in summer, the intake of dissolved effervescent tablets support the daily liquid supply.

• Advantages in case of swallowing problems

• Simple handling and measuring into exact doses

Therefore, the present invention relates to an effervescent tablet (ET) comprising

(i) at least one acid (usually chosen from the group consisting of citric, malic, tartaric, adipic, and fumaric) and

(ii) at least one base (usually chosen from the group consisting of sodium bicarbonate, potassium bicarbonate, sodium carbonate, and potassium carbonate) and

(iii) at least one HMO.

The fast dissolvable tablet according to the present invention is always dissolved in water (or a water-based liquid) before its consumption. This means that the tablet is not swallowed as such.

The acid used in the effervescent tablet according to the present invention is usually used in typical effervescent tablet. Suitable and preferred are citric acid, malic acid, tartaric acid, adipic acid and fumaric acid. Citric acid is the most preferred one.

Therefore, the present invention relates to an effervescent tablet (ET1), which is effervescent tablet (ET), wherein the at least one acid is chosen from the group consisting of citric acid, malic acid, tartaric acid, adipic acid and fumaric acid.

Therefore, the present invention relates to an effervescent tablet (ETT), which is effervescent tablet (ET), wherein the acid is citric acid. The amount of the at least one acid in the effervescent according to the present invention is 20 - 50 weight-% (wt-%), based on the total weight of the effervescent tablet.

A preferred amount of the at least one acid in the effervescent according to the present invention is 25 - 45 wt-%, based on the total weight of the effervescent tablet.

Therefore, the present invention relates to an effervescent tablet (ET2), which is effervescent tablet (ET), (ET1) or (ETT), wherein the amount of the at least one acid is 20 - 50 wt-%, based on the total weight of the effervescent tablet.

Therefore, the present invention relates to an effervescent tablet (ET2’), which is effervescent tablet (ET), (ET1) or (ETT), wherein the amount of the at least one acid is 25 - 45 wt-%, based on the total weight of the effervescent tablet.

The base used in the effervescent tablet according to the present invention is usually used in typical effervescent tablet. Suitable and preferred are sodium bicarbonate, potassium bicarbonate, sodium carbonate, and potassium carbonate. Sodium bicarbonate is the most preferred one.

Therefore, the present invention relates to an effervescent tablet (ET3), which is effervescent tablet (ET), (ET1), (ET ), (ET2) or (ET2’), wherein the at least one base is chosen from the group consisting of sodium bicarbonate, potassium bicarbonate, sodium carbonate, and potassium carbonate.

Therefore, the present invention relates to an effervescent tablet (ET3’), which is effervescent tablet (ET), (ET1), (ETT), (ET2) or (ET2’), wherein the base is sodium bicarbonate, potassium bicarbonate.

The amount of the at least one base in the effervescent according to the present invention is 8 - 35 weight-% (wt-%), based on the total weight of the effervescent tablet.

A preferred amount of the at least one base in the effervescent according to the present invention is 19 - 25 wt-%, based on the total weight of the effervescent tablet. Therefore, the present invention relates to an effervescent tablet (ET4), which is effervescent tablet (ET), (ET1), (ETT), (ET2), (ET2’), (ET3) or (ET3’), wherein the amount of the at least one base is 8 - 35 wt-%, based on the total weight of the effervescent tablet.

Therefore, the present invention relates to an effervescent tablet (ET4’), which is effervescent tablet (ET), (ET1), (ETT), (ET2), (ET2’), (ET3) or (ET3’), wherein the amount of the at least one base is 19 - 25 wt-%, based on the total weight of the effervescent tablet.

An essential feature of the effervescent tablets according to the present invention is one or more human milk oligosaccharides (HMO).

Human milk oligosaccharides (HMOs) are a family of structurally diverse unconjugated gly- cans that are highly abundant in and unique to human milk. Originally, HMOs were proposed to be prebiotic "bifidus factors," or human milk glycans found to promote growth in Bifidobac- terial species of the gut and found uniquely in the stool of breast-fed infants compared to formula fed infants.

HMOs are composed of the five monosaccharides glucose (Glc), galactose (Gal), N-acetyl- glucosamine (GlcNAc), fucose (Fuc) and sialic acid (Sia), with N-acetylneuraminic acid (Neu5Ac) as the predominant if not only form of Sia. More than two hundred different HMOs have been identified so far. The most important ones are 2'-fucosyllactose (2' FL), lacto-N- neotetraose (LNnT), 3-fu cosy I lactose (3FL), difucosyllactose (DFL), Lacto-N-fucopentaose I (LNFP I), 3 ^' Sialyllactose Sodium Salt (3'SL), 6 ^' Sialyllactose Sodium Salt (6'SL), and Lacto- N-Tetraose (LNT).

HMOs can be isolated from breast milk, or they can be produced chemically or biochemically. HMOs are available commercially from a variety of producers.

For the purpose of the present invention the source of the HMO is not essential. It is clear that HMOs from different sources can be used.

Several studies have reported the health benefits of HMOs, which include modulation of the intestinal microbiota, anti-adhesive effect against pathogens, modulation of the intestinal ep ithelial cell response, and development of the immune system.

Therefore, HMOs have very positive effect when consumed by humans and/or animals. Therefore the present invention relates to an effervescent tablet (ET5), which is effervescent tablet (ET), (ET1), (ETT), (ET2), (ET2’), (ET3), (ET3’), (ET4) or (ET4’), wherein the HMO are chosen from the group consisting of 2'-fucosyllactose (2' FL), lacto-N-neotetraose (LNnT), 3- fucosyllactose (3FL), difucosyl-lactose (DFL), Lacto-N-fucopentaose I (LNFP I), 3 ^' Sialyllac- tose Sodium Salt (3'SL), 6 ^' Sialyllactose Sodium Salt (6'SL), and Lacto-N-Tetraose (LNT).

Therefore the present invention relates to an effervescent tablet (ET5’), which is effervescent tablet (ET), (ET1), (ETT), (ET2), (ET2’), (ET3), (ET3’), (ET4) or (ET4’), wherein the HMO are chosen from the group consisting of 2'-fucosyllactose (2' FL), lacto-N-neotetraose (LNnT), 3- fucosyllactose (3FL), difucosyl-lactose (DFL), Lacto-N-fucopentaose I (LNFP I), and Lacto-N- Tetraose (LNT).

Therefore, the present invention relates to an effervescent tablet (ET5”), which is effervescent tablet (ET), (ET1), (ETT), (ET2), (ET2’), (ET3), (ET3’), (ET4) or (ET4’), wherein the HMO is 2'-fucosyllactose (2' FL).

The amount of the at least one HMO in the effervescent according to the present invention is 10 - 45 weight-% (wt-%), based on the total weight of the effervescent tablet.

A preferred amount of the at least one HMO in the effervescent according to the present invention is 15 - 35 weight-% (wt-%), based on the total weight of the effervescent tablet.

Therefore, the present invention relates to an effervescent tablet (ET6), which is effervescent tablet (ET), (ET1), (ETT), (ET2), (ET2’), (ET3), (ET3’), (ET4), (ET4’), (ET5), (ET5’) or (ET5”), wherein the amount of the at least one HMO is 10 - 45 wt-%, based on the total weight of the effervescent tablet.

Therefore the present invention relates to an effervescent tablet (ET6’), which is effervescent tablet (ET), (ET1), (ETT), (ET2), (ET2’), (ET3), (ET3’), (ET4), (ET4’), (ET5), (ET5’) or (ET5”), wherein the amount of the at least one HMO is 15 - 35 wt-%, based on the total weight of the effervescent tablet.

The effervescent tablet according to the present invention can also comprise further ingredi ents, such as binders (or diluents), lubricants, colors, sweeteners, flavors, other active healthy ingredients (such as vitamins, carotenoids, PUFAs, etc.). Binders and diluents are seen as similar compounds in the context of the present invention. So, the term binders also cover diluents.

Binders used in an effervescent tablet can be natural as well as synthetic. Suitable binders/diluents are for example sucrose, mannitol, sorbitol, (liquid) glucose, gum acacia, tragacanth, gelatin, (pregelatinized) starches, alginic acid, cellulose, methyl cellulose, ethyl cellulose, hydroxy propyl methyl cellulose (HPMC), hydroxy propyl cellulose, sodium carboxy methyl cellulose, microcrystalline cellulose (MCC), polyvinyl pyrrolidone (PVP), polyethylene glycol (PEG), polyvinyl alcohols and polymethacrylates.

The amount of binder used in the effervescent tablet according to the present invention is about 5 - 35 wt-%, based on the total weight of the effervescent tablet. Preferably 8 - 25 wt- %, based on the total weight of the effervescent tablet.

Therefore, the present invention relates to an effervescent tablet (ET7), which is effervescent tablet (ET), (ET1), (ETT), (ET2), (ET2’), (ET3), (ET3’), (ET4), (ET4’), (ET5), (ET5’), (ET5”), (ET6) or (ET6’), wherein the effervescent tablet comprises at least one binder.

Therefore the present invention relates to an effervescent tablet (ET7’), which is effervescent tablet (ET7), wherein the binder is chosen from sucrose, mannitol, sorbitol, (liquid) glucose, gum acacia, tragacanth, gelatin, (pregelatinized) starches, alginic acid, cellulose, methyl cellulose, ethyl cellulose, hydroxy propyl methyl cellulose (HPMC), hydroxy propyl cellulose, sodium carboxy methyl cellulose, microcrystalline cellulose (MCC), polyvinyl pyrrolidone (PVP), polyethylene glycol (PEG), polyvinyl alcohols and polymethacrylates.

Therefore, the present invention relates to an effervescent tablet (ET7”), which is effervescent tablet (ET7) or (ET7’), wherein the amount of binder is 5 - 35 wt-%, based on the total weight of the effervescent tablet.

Therefore, the present invention relates to an effervescent tablet (ET7’”), which is effervescent tablet (ET7) or (ET7’), wherein the amount of binder is 8 - 25 wt-%, based on the total weight of the effervescent tablet.

The effervescent tablets according to the present invention can also comprise at least one lubricant. Suitable lubricants are for example talc, magnesium stearate (MGS), polyethylene glycol (PEG), and sodium benzoate (SBZ).

Such lubricants are used in an amount of 0.05 to 5 wt-%, based on the total weight of the effervescent tablet. Preferably, 0.1 to 2 wt-%, based on the total weight of the effervescent tablet.

Therefore the present invention relates to an effervescent tablet (ET8), which is effervescent tablet (ET), (ET1), (ETT), (ET2), (ET2’), (ET3), (ET3’), (ET4), (ET4’), (ET5), (ET5’), (ET5”), (ET6), (ET6’), (ET7), (ET7’), (ET7”) or (ET7’”), wherein the effervescent tablet comprises at least one lubricant.

Therefore, the present invention relates to an effervescent tablet (ET8’), which is effervescent tablet (ET8), wherein the at least one lubricant is chosen from the group consisting of talc, magnesium stearate (MGS), polyethylene glycol (PEG), and sodium benzoate (SBZ).

Therefore, the present invention relates to an effervescent tablet (ET8”), which is effervescent tablet (ET8) or (ET8’), wherein the amount of lubricant is 0.05 to 5 wt-%, based on the total weight of the effervescent tablet.

Therefore, the present invention relates to an effervescent tablet (ET8’”), which is efferves cent tablet (ET8) or (ET8’), wherein the amount of lubricant is 0.1 to 2 wt-%, based on the total weight of the effervescent tablet.

As stated above the effervescent tablet according to the present invention can also comprise dyestuff (color), sweeteners and/or flavors.

Therefore the present invention relates to an effervescent tablet (ET9), which is effervescent tablet (ET), (ET1), (ETT), (ET2), (ET2’), (ET3), (ET3’), (ET4), (ET4’), (ET5), (ET5’), (ET5”), (ET6), (ET6’), (ET7), (ET7’), (ET7”), (ET7’”), (ET8), (ET8’), (ET8”) or (ET8’”), wherein the effervescent tablet comprises at least one dyestuff.

Therefore, the present invention relates to an effervescent tablet (ET9’), which is effervescent tablet (ET9), wherein the amount of the dyestuff is up to 5 wt-%, based on the total weight of the effervescent tablet. Therefore the present invention relates to an effervescent tablet (ET10), which is effervescent tablet (ET), (ET1), (ETT), (ET2), (ET2’), (ET3), (ET3’), (ET4), (ET4’), (ET5), (ET5’), (ET5”), (ET6), (ET6’), (ET7), (ET7’), (ET7”), (ET7’”), (ET8), (ET8’), (ET8”), (ET8’”), (ET9) or (ET9’), wherein the effervescent tablet comprises at least one sweetener and/or flavor.

Therefore, the present invention relates to an effervescent tablet (ET10’), which is effervescent tablet (ET10), wherein the amount of the sweetener and/or flavor is up to 5 wt-%, based on the total weight of the effervescent tablet.

The effervescent tablet according to the present invention can also comprise other active healthy ingredients (next to the HMO(s)).

Such active healthy ingredients are for example vitamins, carotenoids, minerals or PUFAs. The vitamins according to the present invention can be fat-soluble as well as water-soluble. The fat-soluble vitamins are selected from the group consisting of vitamin A, D, E and K. These vitamins are usually used as a preformulated form in the tablet.

The water-soluble vitamins are selected from the group consisting of vitamin B1 (thiamine), vitamin B2 (riboflavin), vitamin B3 (niacin, niacinamide), vitamin B5 (pantothenic acid), vitamin B6 (pyridoxine, pyridoxamine, pyridoxal), vitamin B7 (biotin), vitamin B9 (folic acid, folinic acid), vitamin B12 (cyanocobalamin, hydroxycobalamin, methylcobalamin), and vitamin C (ascorbic acid).

Carotenoids are chosen from the group consisting of beta-carotene, lycopene, lutein, bixin, astaxanthin, apocarotenal, beta-apo-8’-carotenal, beta-apo-12’-carotenal, canthaxanthin, cryptoxanthin, citranaxanthin and zeaxanthin. These carotenoids are usually used as preformulated form in the tablet.

The minerals, which are added to the formulation are Sodium, Potassium, Calcium, Iron, Zinc, and Magnesium.

A suitable trace element is for example iodine.

Therefore the present invention relates to an effervescent tablet (ET11), which is effervescent tablet (ET), (ET1), (ETT), (ET2), (ET2’), (ET3), (ET3’), (ET4), (ET4’), (ET5), (ET5’), (ET5”), (ET6), (ET6’), (ET7), (ET7’), (ET7”), (ET7’”), (ET8), (ET8’), (ET8”), (ET8’”), (ET9), (ET9’), (ET10) or (ET10’), wherein the effervescent tablet comprises at least one healthy ingredient chosen from the group consisting of vitamins, carotenoids, minerals and PUFAs. Therefore, the present invention relates to an effervescent tablet (ET1 T), which is effervescent tablet (ET 11), wherein the amount of the vitamins, carotenoids, minerals and/or PUFAs is up to 5 wt-%, based on the total weight of the effervescent tablet.

All percentages always add up to 100 in one embodiment.

The effervescent tablet can be any shape. Non-limiting examples of shapes can include round, oblong, oval, square, rectangular, diamond, triangular, five-sided, six-sided, sevensided, eight-sided, irregular, or combinations thereof.

A very usual and preferred form is a round (disc-like) shape

The shape of the effervescent tablet according to the present invention is not an essential feature. But usually it has a disc-like shape having a diameter of up to 3 cm (preferably 1.5 - 2.5 cm) and a thickness of up to 0.8 cm (preferably 0.3 - 0.6 cm) and it has a weight of up to 5 g (preferably 0.2 - 5g).

Therefore the present invention relates to an effervescent tablet (ET12), which is effervescent tablet (ET), (ET1), (ETT), (ET2), (ET2’), (ET3), (ET3’), (ET4), (ET4’), (ET5), (ET5’), (ET5”), (ET6), (ET6’), (ET7), (ET7’), (ET7”), (ET7’”), (ET8), (ET8’), (ET8”), (ET8’”), (ET9), (ET9’), (ET10), (ET10’), (ET11) or (ET1 T), wherein the effervescent table has a disc-like shape having a diameter of up to 3 cm (preferably 1.5 - 2.5 cm) and a thickness of up to 0.8 cm (preferably 0.3 - 0.6 cm) and it has a weight of up to 5 g (preferably 0.2 - 5g).

Usually, the tablet according to the present invention is dissolved or dispersed in a glass of water (or water-based liquid), which is usually between 0.1 - 0.4 liter.

The tablets according to the present invention dissolved rapidly. It has similar dissolving properties as a usual effervescent tablet.

The dissolving time is less than 4 minutes (or even less than 2 minutes).

The effervescent tablet according to the present invention is soluble in pure water as well as in water-based solvents. This means the effervescent tablet according to the present invention can also be dissolved in any water-based liquid (such as fruit juices, milk, smoothies, etc). The liquid can be cold or hot. The liquid can be carbonated or non-carbonated.

The effervescent tablets according to the present invention can be produced by using commonly known processes. Usually, the following process steps are used:

(i) Weighing and sieving all ingredients through 1 mm sieve

(ii) Mixing all ingredients

(iii) Pressing the mixture into a tablet form which is wished.

For the present invention the effervescent tablets were compressed with a Korsch XP1 single punch press (Korsch AG, Berlin, Germany) using a round punch set of 25 mm diameter and compression forces between 10 - 40 kN were applied. The invention is illustrated by the following Example.

Example

The amounts for the example are given in Table 1 below. Effervescent tablet mixture for 1000 tablets was prepared by weighing, sieving through 1 mm sieve and mixing the vitamins, Beta Carotene (as colouring), sweetener, Polyethylene Glycol, flavor, silica dioxide and Mannitol for 5 min in a 1 liter vessel with a Turbula mixer (Willy A. Bachofen Maschinenfabrik, Basel, Switzerland). With the addition of GlyCare™ 2FL 9000 (previously weighed and sieved) the mixing system was changed to a larger scale (5 liter vessel) and mixed (tumbler mixer Moser Maschinenbau, Oberwil, Switzerland) for 5 min. Fi nally, Citric Acid, Sodium bicarbonate and Sorbitol were weighed, sieved and added and the mixing conducted for another 10 min in the 10 I vessel with the same tumbler mixer.

Tablets were compressed with a Korsch XP1 single punch press (Korsch AG, Berlin, Ger- many) using a round punch set of 25 mm diameter and a compression force of 30 kN was applied.

Table 1 : Tablet composition per tablet Upon compression the tablet characteristics were determined. Table 2 represents the stand ard characteristics of the tablets, such as tablet weight, tablet hardness and disintegration time, which all comply with the pharmacopoeial requirements for immediate release dosage forms.

Table 2: Tablet characteristics of tablet of table 1