Fast dissolving solid compositions of high molecular weight hyaluronic acid

Abstract

The present invention relates to fast dissolving powder combinations or compositions of high molecular weight hyaluronic acid (HMW-HA) and to processes for preparing HMW-HA water-based fluid compositions comprising them such as a drinkable composition, e.g., a ready to drink (RTD) beverage or another water-based fluid product for oral use containing HMW-HA, or water-based HMW-HA spray product for topical use. The drinkable HMW-HA water-based fluid compositions, for example a RTD beverage of HMW-HA, obtained using the fast-dissolving solid combinations or compositions of the invention are useful for, but not limited to, joint health, skin care, anti-aging. The fast-dissolving solid combinations or compositions of high molecular weight hyaluronic acid (HMW-HA) of the present invention can also be advantageously used for the preparation of a water-based HMW-HA spray product (e.g., a mouth spray, a topical spray for the skin or joints, a lung spray).

Description

[0001] FAST DISSOLVING SOLID COMPOSITIONS OF HIGH MOLECULAR WEIGHT HYALURONIC ACID

[0002] The present invention relates to fast dissolving powder combinations or compositions of high molecular weight hyaluronic acid (HMW-HA) and to processes for preparing HMW-HA water-based fluid compositions comprising them such as a drinkable composition, e.g., a ready to drink (RTD) beverage or another water-based fluid product for oral use containing HMW-HA, or water-based HMW-HA spray product for topical use. The drinkable HMW-HA water-based fluid compositions, for example a RTD beverage of HMW-HA, obtained using the fast-dissolving solid combinations or compositions of the invention are useful for, but not limited to, joint health, skin care, anti-aging. The fast-dissolving solid combinations or compositions of high molecular weight hyaluronic acid (HMW-HA) of the present invention can also be advantageously used for the preparation of a water-based HMW-HA spray product (e.g., a mouth spray, a topical spray for the skin or joints, a lung spray).

[0003] BACKGROUND OF THE INVENTION

[0004] Hyaluronic acid is a linear heteropolysaccharide (glycosaminoglycan -GAG) formed by regularly repeating residues of N-acetyl-D-glucosamine and D-glucuronic acid.

[0005] Depending on the number of repeating residues of N-acetyl-D-glucosamine and D-glucuronic acid, hyaluronic acid (HA) can be classified as low molecular weight HA (LMW-HA), having MW 20-500 kDa, medium molecular weight HA (MMW-HA), having MW 500-1 ,000 kDa, and high molecular weight HA (HMW-HA), having MW 1 ,000-10,000 kDa.

[0006] Hyaluronic acid can be found in the human body i.e., joints (synovial fluid), skin and eye.

[0007] Mechanisms underlying HA depolymerization (i.e. HA molecular weight reduction) are both enzymatic and non- enzymatic. The enzymes that degrade hyaluronic acid are hyaluronidases, chondroitinases and hexosaminidases. The low-molar-mass oligosaccharides resulting from HA degradation appear to function as endogenous danger signals.

[0008] HMW-HA can also be naturally degraded in the organism by ROS, including superoxide, hydrogen peroxide, nitric oxide, peroxynitrite and hypohalous acids, which are massively produced during inflammatory responses, tissue injury and tumorigenesis.

[0009] The molecular weight of hyaluronic acid plays a fundamental role concerning the biological functions in the body and hyaluronic acid fragmentation has biological consequences. For example, LMW hyaluronan can stimulate the production of proinflammatory cytokines, chemokines and growth factors [Rayahin JE, Buhrman JS, Zhang Y, Koh T J, Gemeinhart RA. High and low molecular weight hyaluronic acid differentially influence macrophage activation, ACS Biomater Sci Eng. 2015 Jul 13;1 (7):481-493],

[0010] Biological and physico-chemical benefits of hyaluronic acid depend on the HA molecular weight, with HMW-HA being advantageous compared to LMW-HA.

[0011] Hyaluronic acid of high molecular size (e.g. > 1 ,000 kDa) is present in intact tissues and is antiangiogenic (blocking the growth of new blood vessel) and immunosuppressive, whereas smaller polymers of hyaluronic acid are distress signals and potent inducers of inflammation and angiogenesis. While our bodily systems readily recognize HMW- HA (because that's what is predominantly produce naturally), LMW-HA can easily confuse our bodily systems and can be misidentified (hyalogic, The Benefits Of High-Molecular-Weight Hyaluronic Acid, URL: https: / / hvaloqic.com / bloq / the-benefits-of-hiqh-molecular-weiqht-hyaluronic-acid / ).

[0012] Hyaluronic acid with high molecular weight has a higher cohesive level than hyaluronic acid with low molecular weight (cohesive forces are the forces that keep the same type of molecules together). Briefly, polymer chains with high molecular weight hyaluronic acid start to entangle each other, resulting in the formation of a taught three- dimensional structure that holds itself as a complete whole (cohesive gel), especially when it is impacted by external action. By contrast, solutions with lower molecular weight hyaluronic acid do not have the same value of chain entwinement (Snetkov, et al; Hyaluronic Acid: The Influence of Molecular Weight on Structural, Physical, Physico- Chemical, and Degradable Properties of Biopolymer, Polymers (2020), 12, 1800).

[0013] HMW-HA has also important and beneficial roles in tissue injury and repair and wound healing (Fallacara, et al; Hyaluronic Acid in the Third Millennium) Polymers (2018), 10(7), 701).

[0014] HMW-HA forms a viscous, meshwork around cells in a dose-dependent manner, restricting movement of reactive oxygen species. Reactive oxygen species are responsible for a breakdown of hyaluronic acid to small fragments (Weindl, et. al; Hyaluronic Acid in the Treatment and Prevention of Skin Diseases: Molecular Biological, Pharmaceutical and Clinical Aspects,' Skin Pharmacol. Physiol. (2004), 17, 207-213).

[0015] Orally ingested LMW-HA has shown some disadvantageous effects: some studies have reported inflammatory properties with the activation of the immune response (Fallacara, et al; Hyaluronic Acid in the Third Millennium,' Polymers (2018), 10(7), 701).

[0016] Moreover, there some studies confirming that orally administered HMW-HA may reach joints, bones and skin, even if in small amounts, thus highlighting that a rationale may exist in the use of HMW-HA-based food supplements designed for joint and / or skin health and / or lung health.

[0017] Oral administration of HMW-HA, advantageous over LMW HA for the above reasons, poses challenging technical problems.

[0018] The behavior of hyaluronic in water depends on the molecular weight. Increasing the molecular weight changes the viscosity from fluids to gels. Low molecular weight hyaluronic acids (LMW-HA) have a viscosity comparable to water. With increasing molecular weight and concentration, hyaluronic acid solutions display progressively an increased viscosity and viscoelastic behavior. A HMW hyaluronic acid (e.g. >1,000 kDa) forms an extended network (a gel) even at a very low concentration of 1 pig / mL

[0019] Solid (e.g., powder) compositions for instant (or RTD, ready to drink) beverage are particularly advantageous and offer great compliance for those taking them. They are easy to prepare, stable, easy to swallow and suitable for a wide range of individuals, including the elderly and children. Usually, they can be poured into water, or another water-based fluid, and quickly and easily, with the only aid of a spoon, transformed into a drinkable fluid having an appealing mouthfeel, taste and colour.

[0020] To have a healthy effect from the HA, it is preferred to use a high molecular weight HA but due to this high molecular weight, the dissolution or gel formation of HMW-HA powder as such in a water-based fluid is very difficult for a consumer, and the formation of lumps (agglomeration of HMW-HA in water) is a further disadvantage. Furthermore, the resulting gel (if any) is very stiff and does not flow easily out of the drinking glass to the mouth.

[0021] Furthermore, for a spray product (based on an HMW-HA and water) where a liquid or a fluid gel is of advantage (e.g., a mouth spray, a topical spray for the skin or joints, a lung spray) it is difficult to dissolve it only in water using only the pure HMW-HA.

[0022] For these reasons, despite its interesting beneficial properties, the HMW-HA powder used as such shows many drawbacks.

[0023] The products on the markets based on HMW-HA for oral use are typically in a capsule form (avoiding the difficulty of dissolution of HMW-HA in a water-based liquid). However, capsules are not suitable to be administered to some categories of subject, particularly to subject with swallowing problems, e.g. the elderly.

[0024] CN116114881 A discloses a three-layer tablet provided with an upper layer, a middle layer and a lower layer which are sequentially stacked: the middle layer contains hyaluronic acid or salt thereof and probiotics, the upper layer and the lower layer are an acid layer and an alkaline layer respectively, and the acid layer and the alkaline layer are sequentially stacked. Said three-layer tablet comprises carboxymethyl cellulose (CMC), which is a gel forming ingredient.

[0025] CN116114881 A does not disclose a fast-dissolving powder composition comprising high molecular weight hyaluronic acid (HMW-HA).

[0026] CN110960497 B discloses a hyaluronic acid buccal tablet and a preparation method thereof. The hyaluronic acid buccal tablet comprises high-molecular-weight hyaluronic acid or salt thereof, as well as higher amounts of low- molecular-weight hyaluronic acid or salt thereof.

[0027] CN110960497 B does not disclose a fast-dissolving powder composition comprising high molecular weight hyaluronic acid (HMW-HA).

[0028] JP2003095955 A discloses a composition containing sodium hyaluronate and A method for stabilizing a hyaluronic acid-containing solid composition, which comprises freeze-drying an aqueous solution containing one or more sugars.

[0029] JP2003095955 A does not disclose a drinkable HMW-HA water-based fluid composition for oral use comprising high molecular weight hyaluronic acid (HMW-HA).

[0030] US10849923 B1 discloses a solid dry powder formulation consisting of hyaluronic acid and potassium sorbate and alpha-cyclodextrin and citric acid and sodium benzoate and sodium chloride and D-mannitol and optionally sorbitol. The formulation is dissolved in water after 1-3 hours (column 10).

[0031] Therefore, US10849923 B1 does not disclose a fast dissolving powder composition comprising high molecular weight hyaluronic acid (HMW-HA).

[0032] WO2018100469 A1 discloses a composition comprising hyaluronic acid, a natural molecule (glycosaminoglycan, glycoprotein, keratin, collagen, and mixtures thereof), and at least a thickening agent (gum arable). The composition is for use in the treatment of gastroesophageal reflux.

[0033] Consumers nowadays prefer liquid formulations, ready-to-drink versions, beverages, powders that can be dissolved in water (or other water-based fluids). The products on the markets based on solid HA composition for instant (or RTD, ready to drink) beverage contain HA having MW 200-1 ,000 kDa, which can be more easily dissolved when poured into water, or another waterbased fluid. However, the beneficial effects of administration of HA having MW 200-1 ,000 kDa are inferior (if not deleterious) compared to those obtained by administering HMW-HA.

[0034] The technical problem that the present invention addresses and solves is to provide a fast dissolving solid combination or composition of high molecular weight hyaluronic acid (HMW-HA) in the form of a mixture of powders and / or granules, useful for preparing, for example, RTD beverage or another water-based fluid product for oral use containing HMW-HA, that is easy to prepare (also with the only aid of a spoon), stable, easy to swallow and with an appealing mouthfeel, taste and colour.

[0035] The fast-dissolving solid combination or composition of high molecular weight hyaluronic acid (HMW-HA) in the form of a mixture of powders and / or granules of the present invention can also be advantageously used for the preparation of a water-based HMW-HA spray product (e.g., a mouth spray, a topical spray for the skin or joints, a lung spray).

[0036] It is also known a process for preparing HA that is disclosed in W02020 / 245809 A2 which is herewith incorporated by reference.

[0037] It is also known a process for preparing HA that is disclosed in WO2021 / 250566 A1 which is herewith incorporated by reference.

[0038] Scientific papers having title " New Hyaluronic Acid from Plant Origin to Improve Joint Protection— An In Vitro Stud / , in the name of R- Galla et al., (published 23 July 2022); and “Non-Animal Hyaluronic Acid and Probiotics Enhance Skin Health via the Gut-Skin Axis: An In Vitro Study on Bioavailability and Cellular Impact’, in the name of R. Galla et al., (published 22 January 2025) are also herewith incorporated by reference.

[0039] BRIEF DESCRIPTION OF THE DRAWINGS

[0040] Fig. 1A and Fig. 1 B shows the slow dissolution behaviour in water of an HMW-HA powder (Greenluronic®; MW 1 ,600-4,000 kDa), both with the aid of a spoon (poor dissolution behaviour) and an industrial mixer (a very stiff hydrogel is obtained).

[0041] Fig 1A, left side, demonstrates that with a lab mixer (or industrial mixer for larger quantities) it is possible to dissolve the HMW-HA (like Greenluronic® or other HMW-HA) under high speed and get the corresponding HMW-HA gel. Fig 1 A, right side, demonstrates that it is not possible by simply stirring with a spoon for a consumer to dissolve an HMW-HA like Greenluronic® or other commercially available HMA-HAs.

[0042] Fig 1 B demonstrates the whole process of taking the powder of an HMW-HA (Greenluronic®) and put this powder into water in a beverage glass and stir this composition with a spoon. Lump formation is the result.

[0043] Fig. 2 shows the dissolution behaviour in water of an HMW-HA powder (Greenluronic®; MW 1 ,600-4,000 kDa) in its RTD beverage grade (combination or composition according to the present invention; good dissolution behaviour even with the only aid of a spoon) and as standard grade powder (not according to the present invention; a stiff hydrogel is obtainable only with the aid of an industrial mixer). Fig. 3A and Fig. 3B show some examples of RTD beverages easily obtained using the HMW-HA fast dissolving solid combinations or compositions in the form of a mixture of powders and / or granules of the invention, optionally including flavors / colorants (Fig. 3A including vanilla flavor; Fig. 3B includes yellow lemon (I), raspberry (II) and strawberry (ill) flavors).

[0044] Fig. 4 shows the intestinal absorption between Greenluronic® (an embodiment of the present invention) and sodium hyaluronate.

[0045] Fig. 5 shows the efficacy on osteoarthritic model (Fig. 5A shows the cell proliferation; Fig. 5B shows the HA quantification).

[0046] Fig. 6 shows the efficacy on osteoarthritic model (Fig. 6A shows the CD44A activity Vs. Control (%); Fig. 6B shows the inflammation level Vs. Control (%).

[0047] Fig. 7 shows the effect on skin (Fig. 7A shows the ROS production in NHEK keratinocytes cell line; Fig. 7B shows the inflammation levels in NHEK keratinocytes cell line).

[0048] Fig. 8 shows the effect on skin (Fig. 8A shows the cells proliferation in NHEK keratinocytes cell line skin injury model; Fig. 8B shows the KI67 in NHEK keratinocytes cell line skin injury model).

[0049] Fig. 9 shows the effect on collagen production i.e. , the collagen quantification NHEK keratinocytes cell line.

[0050] Fig. 10 shows the skin regeneration (1) control; (2) Greenluronic embodiment of the present invention; (3) sodium hyaluronate.

[0051] DETAILED DESCRIPTION OF THE INVENTION

[0052] As a result of extensive research and development, the Applicant addresses and solves the above requirements by providing an innovative combination that allows HMW-HA fast dissolving solid composition, in the form of a mixture of powders and / or granules, to be quickly and easily diluted in a fluid, preferably water, resulting in a drinkable, stable and easy-to-take composition or, alternatively, in a water-based HMW-HA spray product (e.g., a mouth spray, a topical spray for the skin or joints, a lung spray).

[0053] The HMW-HA fast dissolving solid combination, in the form of a mixture of powders and / or granules, of the invention by adding a fluid leads preferably to:

[0054] - a fluid HMW-HA composition, or

[0055] - a fluid gel HMW-HA composition, or

[0056] - an effervescent fluid HMW-HA composition (e.g., if the HMW-HA powder composition contains an effervescent system), or

[0057] - an effervescent fluid gel HMW-HA composition (e.g., if the HMW-HA powder composition contains an effervescent system).

[0058] In the context of the present invention the "solid” fast dissolving combinations or compositions of high molecular weight hyaluronic acid (HMW-HA) is only in the form of powders or granules, preferably powders, not in the form of a solid tablet or pill. This is because the powders are dissolved very fast in a liquid at room temperature of 18°C- 25°C and provide a Ready to drink (RTD) composition in a very short time e.g., from 30 seconds to 180 seconds. It is not a solid tablet to be swallowed with water, but instead it is a powder that is dissolved in liquid (e.g., water or milk) and then drunk.

[0059] Further, gelling or thickening agents such as, for example CMC (Carboxymethyl cellulose) or NaCMC (Carboxymethyl cellulose of sodium salt) cannot be used in the context of the present invention because their use provides a gel and not a liquid composition RTD. The HA forms a gel when it is added to a liquid e.g., water or milk. The purpose of the present invention is to obtain a liquid, and not a gel.

[0060] In the context of the present invention, the term "fluid” may have, for example, the meaning of water, a translucent / transparent or coloured water-based system, a milk (white fluid), a fluid similar to milk (milk substitute, plant-based milk, non dairy substitute, non-dairy beverage, instant milk), a beverage (non-alcoholic, alcoholic), a drink (fruit drink, energy drink, fortified drink, herbal drink, sport drink, yogurt drink, buttermilk drink, probiotic drink), a nectar, a juice a coffee, a cappuccino, a smoothie, a macchiato, a cafe au lait, a coffee milk, a frapuccino, an espresso, an espresso macchiato, a latte espresso, a flat white, a caffee latte, a cacao.

[0061] In the context of the present invention, the term "fluid gel” may have, for example, the meaning of a system that is not a stiff gel (not flowable) but a flowable system (e.g., from a beverage glass so that a consumer can easily drink it). A fluid gel is a translucent / transparent gel (water based HMW-HA system) or a white composition (milk-like appearance) with higher viscosity so that a fluid gel-like HMW-HA composition results that is drinkable) or a coloured fluid gel HMW-HA composition so that a coloured fluid gel HMW-HA composition results that is drinkable. Preferably, a fluid gel of the invention may contain an effervescent system (e.g., mousse-like transparent or white or coloured appearance). A mousse is a soft, light, and airy system, that may contain bubbles of CO2 to give it a light and airy texture.

[0062] In the context of the present invention, the term "fluid composition” and "fluid gel composition” mean that they flow easily out from the drinking glass (or other containers) to the mouth of a consumer or from a spoon to the mouth of the consumer.

[0063] The fluid or the fluid gel can be used for a spray application (e.g., a mouth spray, a topical spray for the skin or joints, a lung spray).

[0064] The Applicant has found a solid fast dissolving combination in the form of a mixture of powders and / or granules (e.g., a powder) comprising HMW-HA that is able to be quickly and easily diluted in a water-based fluid (e.g., water) resulting in a drinkable, stable and easy-to-take composition, without lumps formation despite the viscosity of HMW- HA, having an improved mouthfeel, taste, and colour of the final HMW-HA drinkable composition; or in water-based HMW-HA spray product for topical use.

[0065] In the context of the present invention, the expression "fast dissolving” means that, when a solid combination or composition in the form of a mixture of powders and / or granules of the invention is poured into a water-based fluid at a temperature comprised from 18 °C to 40°C, preferably comprised from 18°C to 25 °C, and stirred, preferably with the aid of a spoon, it easily gives, within a time from 10 seconds to 5 minutes, preferably from 1 minute to 3 minutes, a solution or a homogeneous fine dispersion free of lumps, insoluble bottom residue, precipitates.

[0066] All the components of the solid fast dissolving composition of the present invention are in a powder form and / or in a granular form, to give a solid fast dissolving composition of the present invention in the form of a mixture of powders and / or granules. In the context of the present invention, the expressions "solid fast dissolving composition” and / or "solid fast dissolving combination” are intended to refer to and include any solid composition or combination of the present invention that is in the form of a loose and / or free-flowing mixture of powders and / or granules, i.e. it is not a in the form of a tablet, a chewable tablet, a pill, a candy, a capsule, etc.

[0067] According to the present invention, the fast dissolving powder composition comprises or, alternatively, consists of high molecular weight hyaluronic acid (HMW-HA) having an average molecular weight equal to or bigger than 1 ,000 kDa to 10,000 kDa in combination with at least one dissolving aid component which is selected from the group comprising or, alternatively, consisting of:

[0068] (i) an effervescent system that comprises at least one basic substance which is selected from carbonate or bicarbonate, and at least one acid substance which is selected from citric or tartaric acid, and mixtures thereof;

[0069] (ii) at least one water-soluble salt which is selected from a water-soluble alkali-metal citrate salt, a water- soluble alkali-metal gluconate salt, a water-soluble alkali-earth metal citrate salt, a water-soluble alkali-earth metal gluconate salt, and mixtures thereof.

[0070] The high molecular weight hyaluronic acid (HMW-HA) of the combination or composition of the present invention has a molecular weight equal to or bigger than 1 ,000 kDa; preferably, it has a molecular weight comprised from bigger than 1 ,000 kDa to 10,000 kDa; more preferably, it has a molecular weight comprised from 1 ,000 kDa to 8,000 kDa, more preferably, it has a molecular weight comprised from 1 ,000 to 7,000 kDa, even more preferably, it has a molecular weight comprised from 1 ,000 kDa to 6,000 kDa, for example, 1 ,500 kDa, or 2,000 kDa, or 2,500 kDa, or 3,000 kDa, or 3,500 kDa, or 4,000 kDa, or 4,500 kDa, or 5,000 kDa, or 5,500 kDa, or mixtures thereof.

[0071] Preferably, the fast dissolving powder composition comprises or, alternatively, consists of high molecular weight hyaluronic acid (HMW-HA) having an average molecular weight equal to or bigger than 1 ,000 kDa to 10,000 kDa in combination with at least one dissolving aid component selected from (iii) at least one sugar which is selected from the group comprising or, alternatively, consisting of sucrose, lactose, maltose, trehalose, erythritol, xylitol, maltitol, sorbitol, mannitol, or mixtures thereof.

[0072] Moreover, the present invention relates also to a fast-dissolving solid combination (or composition) in the form of a mixture of powders and / or granules comprising or, alternatively, consisting of high molecular weight hyaluronic acid (HMW-HA) in combination with at least one dissolving aid component (i) to (iii) which is selected from group comprising or, alternatively, consisting of: i. an effervescent system, as defined in the present invention, and, optionally, at least one water-soluble salt and / or one sugar and / or an acacia gum, as defined in the present invention; or ii. at least one water-soluble salt, as defined in the present invention, and, optionally, an effervescent system and / or one sugar and / or an acacia gum, as defined in the present invention; or iii. at least one sugar, as defined in the present invention, and, optionally, an effervescent system and / or one water-soluble salt and / or an acacia gum, as defined in the present invention.

[0073] The solid fast dissolving combination (or composition) in the form of a mixture of powders and / or granules comprising or, alternatively, consisting of high molecular weight hyaluronic acid (HMW-HA) in combination with at least one dissolving aid component (i) to (iii) can, optionally, comprise a further ingredient selected from: iv. at least one flavour and / or colorant and / or sweetener and / or oils (lipids) and / or surfactants and / or a carrier and / or at least one excipient of pharmaceutical or food grade; and / or v. at least a pH adjusting agent, preferably an organic acid; more preferably at least one hydroxy acid, e.g., citric acid and / or tartaric acid; and / or vi. at least one further active ingredient, as detailed below in the present document.

[0074] With reference to said at least one dissolving aid component (i) to (iii) and to the at least one optional further ingredient (iv) to (vi), the term "component” or "ingredient” herein includes either a single substance or mixture of substances thereof.

[0075] Preferably, the solid fast dissolving solid HMW-HA composition in the form of a mixture of powders and / or granules of the present invention preferably includes (iv) one or more flavours and / or colorants and / or sweetener and / or oils (lipids) and / or surfactants, e.g. an acacia gum, in order to obtain, for example, an RTD beverage obtained from the fast dissolving solid HMW-HA composition of the present invention that is more appealing in mouthfeel, taste, and colour.

[0076] Preferably, the solid fast dissolving solid HMW-HA composition in the form of a mixture of powders and / or granules of the present invention preferably includes (v) at least one hydroxy acid, e.g., citric acid and / or tartaric acid, for pH adjusting, in the case of a more acidic taste of, for example, the RTD beverage obtained from the fast-dissolving solid HMW-HA composition of the present invention is desirable.

[0077] Preferably, the solid fast dissolving solid HMW-HA composition in the form of a mixture of powders and / or granules of the present invention preferably includes (vi) at least one further active ingredient, in order to obtain an improved biological effect.

[0078] Preferably, the solid fast dissolving combination or composition in the form of a mixture of powders and / or granules of the present invention can be mixed with a drinkable liquid or a drinkable fluid gel like composition, which may be selected from the group comprising or, alternatively, consisting of water, milk (e.g., cow milk), a milk substitute (plant based milk, non dairy substitute, dairy beverage), a carbonated fluid, a beverage, a drink (fruit drink, energy drink, fortified drink, herbal drink, sport drink, yogurt drink, buttermilk drink, probiotic drink), a nectar, a juice, a smoothie, a macchiato, a cafe au lait, a caffee latte, a coffee milk, a frapuccino, an espresso, an espresso macchiato, a latte espresso, a flat white, a cacao, without forming lumps.

[0079] Preferably, the solid fast dissolving combination or composition in the form of a mixture of powders and / or granules of the present invention can be used for the easy preparation of a water-based HMW-HA spray product (e.g., a mouth spray, a topical spray for the skin or joints, a lung spray).

[0080] The skilled person knows that a High molecular weight hyaluronic acid (HMW-HA) is a known and commercially available compound.

[0081] High molecular weight hyaluronic acid (HMW-HA) of the combination or composition of the present invention has a molecular weight equal to or bigger than 1 ,000 kDa; preferably, it has a molecular weight comprised from bigger than 1 ,000 kDa to 10,000 kDa; more preferably, it has a molecular weight comprised from 1 ,000 kDa to 8,000 kDa, more preferably, it has a molecular weight comprised from 1 ,000 to 7,000 kDa, even more preferably, it has a molecular weight comprised from 1 ,000 kDa to 6,000 kDa, for example, 1 ,500 kDa, or 2,000 kDa, or 2,500 kDa, or 3,000 kDa, or 3,500 kDa, or 4,000 kDa, or 4,500 kDa, or 5,000 kDa, or 5,500 kDa, or mixtures thereof.

[0082] Advantageously, the High Molecular Weight Hyaluronic Acid (HMW-HA) has a molecular weight comprised from 1 ,500 kDa to 4,000 kDa; preferably comprised from 2,000 kDa to 3,500 kDa. Advantageously, this High molecular weight hyaluronic acid (HMW-HA) named Greenluronic® is able, among the other, to reduce inflammation, improve lubrication and support cartilage wellbeing.

[0083] Those skilled in the art know that the molecular weight of a polymer is an average molecular weight value. In the context of the present invention, it is intended to refer to the average molecular weight. The person skilled in the art is aware of methods for measuring the average molecular weight of hyaluronic acid and its salts, as these are known techniques in the industry using known equipment. Likewise, the expert in the field is aware that the measurement of chemical and physical parameters of polymers changes depending on the temperature used to determine them. Here, a temperature chosen in the range of from 18°C to 25°C is considered, e.g. 20°C.

[0084] For example, said high molecular weight hyaluronic acid (HMW-HA) can be ExceptionHYAL HW (1 ,800-2,200), that is sodium Hyaluronate with MW 1 ,800-2,200 kDa, or ExceptionHYAL MW (1 ,000-1 ,800), that is sodium Hyaluronate with MW 1 ,000-1,800 kDa, both of them are available into the market since they are produced by Roelmi company.

[0085] As a further example, advantageously said high molecular weight hyaluronic acid (HMW-HA) can be Greenluronic® from Vivatis Pharma company. Greenluronic® is a high molecular weight hyaluronic acid (MW 1 ,500-4,000 kDa) of fungal (Tremella fuciformis) origin.

[0086] Preferably, said an effervescent system mentioned in the components (i) to (iii) above comprises or, alternatively, consists of at least one base that can release carbon dioxide.

[0087] According to the present invention, said an effervescent system comprises or, alternatively, consists of at least one basic substance (i.e., an organic and / or inorganic base) capable of releasing carbon dioxide in the presence of an acidic substance (i.e., an organic and / or inorganic acid) preferably in the presence of a composition or formulation containing water.

[0088] Preferably, said base may be a carbonate and / or bicarbonate salt, more preferably may be a sodium and / or potassium carbonate salt or sodium and / or potassium bicarbonate salt.

[0089] Preferably, said an effervescent system mentioned in the components (i) to (iii) above comprises or, alternatively, consists of a sodium and / or potassium bicarbonate salt (also referred to as sodium or potassium hydrogen carbonate salt, NaHCO3or KHCO3) and citric acid, e.g., anhydrous citric acid, or tartaric acid.

[0090] Preferably, said at least one water-soluble salt mentioned in the component (i) to (iii) above is selected from a water-soluble alkali-metal organic salt and / or a water soluble alkali-earth metal organic salt, more preferably from the group comprising or, alternatively, consisting of gluconate salts, citrate salts, ascorbate salts, lactate salts, tartrate salts, and mixtures thereof; even more preferably, said at least one water-soluble salt mentioned in the component (i) to (iii) above is selected from water-soluble alkali-metal salts of gluconate, water-soluble alkali-metal salts of citrate, water soluble alkali-earth metal salts of gluconate, water soluble alkali-earth metal salts of citrate, and mixture thereof; still even more preferably, said at least one water-soluble salt mentioned in the component (i) to (iii) above is selected from the group comprising or, alternatively, consisting of a sodium gluconate, a potassium gluconate, a potassium citrate, and mixture thereof.

[0091] For example, said at least one water-soluble salt mentioned in the component (I) to (iii) above may be selected from a tripotassium citrate salt and / or tripotassium citrate monohydrate (company Pharmavit or from Magnesia / Jungbunzlauer), a sodium gluconate salt (company Magnesia / Jungbunzlauer), a potassium gluconate salt (company Magnesia / Jungbunzlauer), and mixtures thereof.

[0092] Preferably, said at least one sugar mentioned in the component (I) to (iii) above is selected from a disaccharide, e.g. sucrose, lactose, maltose, trehalose, a sugar alcohol, e.g. erythritol, xylitol, maltitol, sorbitol, mannitol, or mixtures thereof; more preferably said at least one sugar mentioned in the component (I) to (iii) above is selected from sucrose, maltitol, erythritol, xylitol or mixtures thereof.

[0093] Preferably, (A) the invention refers to a solid fast dissolving combination (or composition) in the form of a mixture of powders and / or granules comprising or, alternatively, consisting of high molecular weight hyaluronic acid (HM W- HA) in combination with an effervescent system. Even more preferably, said an effervescent system consists of a bicarbonate salt, e.g., sodium hydrogen carbonate, and citric acid, e.g., anhydrous citric acid, or tartaric acid.

[0094] Preferably, (B) the invention refers to a solid fast dissolving combination (or composition) in the form of a mixture of powders and / or granules comprising or, alternatively, consisting of high molecular weight hyaluronic acid (HM W- HA) in combination with at least one water-soluble salt. Even more preferably, said at least one water-soluble salt is selected from a water-soluble alkali-metal citrate and / or gluconate salt and / or a water-soluble alkali-earth metal citrate and / or gluconate salt, for example tripotassium citrate, tripotassium citrate monohydrate, potassium gluconate, sodium gluconate, or mixtures thereof.

[0095] Preferably, (C) the invention refers to a solid fast dissolving combination (or composition) in the form of a mixture of powders and / or granules comprising or, alternatively, consisting of high molecular weight hyaluronic acid (HM W- HA) in combination with at least one sugar. Even more preferably, said at least one sugar is selected from a disaccharide, e.g. sucrose, a sugar alcohol, e.g. erythritol, xylitol, maltitol, or mixtures thereof.

[0096] Preferably, (D) the invention refers to a solid fast dissolving combination (or composition) in the form of a mixture of powders and / or granules comprising or, alternatively, consisting of high molecular weight hyaluronic acid (HM W- HA) in combination with an effervescent system and at least one water-soluble salt. Even more preferably, said an effervescent system consists of a bicarbonate salt, e.g., sodium hydrogen carbonate, and citric acid, e.g., anhydrous citric acid, or tartaric acid, and said at least one water-soluble salt is selected from a water-soluble alkali- metal citrate and / or gluconate salt and / or a water soluble alkali-earth metal citrate and / or gluconate salt, for example tripotassium citrate, tripotassium citrate monohydrate, potassium gluconate, sodium gluconate, or mixtures thereof. Preferably, (E) the invention refers to a solid fast dissolving combination (or composition) in the form of a mixture of powders and / or granules comprising or, alternatively, consisting of high molecular weight hyaluronic acid (HM W- HA) in combination with an effervescent system and at least one sugar. Even more preferably, said an effervescent system consists of a bicarbonate salt, e.g., sodium hydrogen carbonate, and citric acid, e.g., anhydrous citric acid, or tartaric acid, and said at least one sugar is selected from a disaccharide, e.g. sucrose, a sugar alcohol, e.g. erythritol, xylitol, maltitol, or mixtures thereof. Preferably, (F) the invention refers to a solid fast dissolving combination (or composition) in the form of a mixture of powders and / or granules comprising or, alternatively, consisting of high molecular weight hyaluronic acid (HM W- HA) in combination with an effervescent system and an acacia gum. Even more preferably, said an effervescent system consists of a bicarbonate salt, e.g., sodium hydrogen carbonate, and citric acid, e.g., anhydrous citric acid, or tartaric acid. Acacia gum is a known and commercially available compound, and it is also referred to as gum arabic, and preferably it is present in powder form. Gum arabic is the dried resin of acacia Senegal and related species. Any form of acacia gum can be included in the combination or composition of the present invention, without limitation.

[0097] Preferably, (G) the invention refers to a solid fast dissolving combination (or composition) in the form of a mixture of powders and / or granules comprising or, alternatively, consisting of high molecular weight hyaluronic acid (HM W- HA) in combination with at least one water-soluble salt and at least one sugar. Even more preferably, said at least one water-soluble salt is selected from a water-soluble alkali-metal citrate and / or gluconate salt and / or a water soluble alkali-earth metal citrate and / or gluconate salt, for example tripotassium citrate, tripotassium citrate monohydrate, potassium gluconate, sodium gluconate, or mixtures thereof, and said at least one sugar is selected from a disaccharide, e.g. sucrose, a sugar alcohol, e.g. erythritol, xylitol, maltitol, or mixtures thereof.

[0098] Preferably, (H) the invention refers to a solid fast dissolving combination (or composition) in the form of a mixture of powders and / or granules comprising or, alternatively, consisting of high molecular weight hyaluronic acid (HM W- HA) in combination with at least one water-soluble salt and an acacia gum. Even more preferably, said at least one water-soluble salt is selected from a water-soluble alkali-metal citrate and / or gluconate salt and / or a water-soluble alkali-earth metal citrate and / or gluconate salt, for example tripotassium citrate, tripotassium citrate monohydrate, potassium gluconate, sodium gluconate, or mixtures thereof. Acacia gum is a known and commercially available compound, and it is also referred to as gum arabic, and preferably it is present in powder form. Gum arabic is the dried resin of acacia Senegal and related species. Any form of acacia gum can be included in the combination or composition of the present invention, without limitation.

[0099] Preferably, (I) the invention refers to a solid fast dissolving combination (or composition) in the form of a mixture of powders and / or granules comprising or, alternatively, consisting of high molecular weight hyaluronic acid (HMW- HA) in combination with at least one sugar and an acacia gum. Even more preferably, said at least one sugar is selected from a disaccharide, e.g. sucrose, a sugar alcohol, e.g. erythritol, xylitol, maltitol, or mixtures thereof. Acacia gum is a known and commercially available compound, and it is also referred to as gum arabic, and preferably it is present in powder form. Gum Arabic is the dried resin of acacia Senegal and related species. Any form of acacia gum can be included in the combination or composition of the present invention, without limitation. Preferably, (L) the invention refers to a solid fast dissolving combination (or composition) in the form of a mixture of powders and / or granules comprising or, alternatively, consisting of high molecular weight hyaluronic acid (HM W- HA) in combination with an effervescent system, at least one water-soluble salt and at least one sugar. Even more preferably, said an effervescent system consists of a bicarbonate salt, e.g., sodium hydrogen carbonate, and citric acid, e.g., anhydrous citric acid, or tartaric acid; said at least one water-soluble salt is selected from a water-soluble alkali-metal citrate and / or gluconate salt and / or a water soluble alkali-earth metal citrate and / or gluconate salt, for example tripotassium citrate, tripotassium citrate monohydrate, potassium gluconate, sodium gluconate, or mixtures thereof; and said at least one sugar is selected from a disaccharide, e.g. sucrose, a sugar alcohol, e.g. erythritol, xylitol, maltitol, or mixtures thereof.

[0100] Preferably, (M) the invention refers to a solid fast dissolving combination (or composition) in the form of a mixture of powders and / or granules comprising or, alternatively, consisting of high molecular weight hyaluronic acid (HM W- HA) in combination with an effervescent system, at least one water-soluble salt and an acacia gum. Even more preferably, said an effervescent system consists of a bicarbonate salt, e.g., sodium hydrogen carbonate, and citric acid, e.g., anhydrous citric acid, or tartaric acid; and said at least one water-soluble salt is selected from a water- soluble alkali-metal citrate and / or gluconate salt and / or a water soluble alkali-earth metal citrate and / or gluconate salt, for example tripotassium citrate, tripotassium citrate monohydrate, potassium gluconate, sodium gluconate, or mixtures thereof. Acacia gum is a known and commercially available compound, and it is also referred to as gum arabic, and preferably it is present in powder form. Gum arabic is the dried resin of acacia Senegal and related species. Any form of acacia gum can be included in the combination or composition of the present invention, without limitation.

[0101] Preferably, (N) the invention refers to a solid fast dissolving combination (or composition) in the form of a mixture of powders and / or granules comprising or, alternatively, consisting of high molecular weight hyaluronic acid (HM W- HA) in combination with an effervescent system, at least one sugar and an acacia gum. Even more preferably, said an effervescent system consists of a bicarbonate salt, e.g., sodium hydrogen carbonate, and citric acid, e.g., anhydrous citric acid, or tartaric acid; and said at least one sugar is selected from a disaccharide, e.g. sucrose, a sugar alcohol, e.g. erythritol, xylitol, maltitol, or mixtures thereof. Acacia gum is a known and commercially available compound, and it is also referred to as gum arabic, and preferably it is present in powder form. Gum arabic is the dried resin of acacia Senegal and related species. Any form of acacia gum can be included in the combination or composition of the present invention, without limitation.

[0102] Preferably, (0) the invention refers to a solid fast dissolving combination (or composition) in the form of a mixture of powders and / or granules comprising or, alternatively, consisting of high molecular weight hyaluronic acid (HM W- HA) in combination with at least one water-soluble salt, at least one sugar and an acacia gum. Even more preferably, said at least one water-soluble salt is selected from a water-soluble alkali-metal citrate and / or gluconate salt and / or a water-soluble alkali-earth metal citrate and / or gluconate salt, for example tripotassium citrate, tripotassium citrate monohydrate, potassium gluconate, sodium gluconate, or mixtures thereof; and said at least one sugar is selected from a disaccharide, e.g. sucrose, a sugar alcohol, e.g. erythritol, xylitol, maltitol, or mixtures thereof. Acacia gum is a known and commercially available compound, and it is also referred to as gum arabic, and preferably it is present in powder form. Gum Arabic is the dried resin of acacia Senegal and related species. Any form of acacia gum can be included in the combination or composition of the present invention, without limitation. Preferably, (P) the invention refers to a solid fast dissolving combination (or composition) in the form of a mixture of powders and / or granules comprising or, alternatively, consisting of high molecular weight hyaluronic acid (HM W- HA) in combination with an effervescent system, at least one water-soluble salt, at least one sugar and an acacia gum. Even more preferably, said an effervescent system consists of a bicarbonate salt, e.g., sodium hydrogen carbonate, and citric acid, e.g., anhydrous citric acid, or tartaric acid; said at least one water-soluble salt is selected from a water-soluble alkali-metal citrate and / or gluconate salt and / or a water soluble alkali-earth metal citrate and / or gluconate salt, for example tripotassium citrate, tripotassium citrate monohydrate, potassium gluconate, sodium gluconate, or mixtures thereof; and said at least one sugar is selected from a disaccharide, e.g. sucrose, a sugar alcohol, e.g. erythritol, xylitol, maltitol, or mixtures thereof. Acacia gum is a known and commercially available compound, and it is also referred to as gum arable, and preferably it is present in powder form. Gum arable is the dried resin of acacia Senegal and related species. Any form of acacia gum can be included in the combination or composition of the present invention, without limitation.

[0103] Preferably, (Q) the invention refers to one of the above solid fast dissolving combinations (or compositions) in the form of a mixture of powders and / or granules from (A) to (P) in combination with one or more flavours and / or colorants and / or sweetener and / or pH adjusting agents, preferably a hydroxy acid, and / or surfactants and / or further actives, as defined herein.

[0104] The solid fast dissolving combination in the form of a mixture of powders and / or granules of the invention may be present in a composition for oral use such as a solid pharmaceutical, nutraceutical or food composition which comprises an aforementioned component (I) to (ill) as above defined, and optionally, (iv) at least one flavour and / or colorant and / or sweetener and / or oils (lipids) and / or surfactants and / or a carrier or at least one excipient of pharmaceutical or food grade; and / or (v) at least a pH adjusting agent, preferably an organic acid; more preferably at least one hydroxy acid, e.g., citric acid and / or tartaric acid; and / or (vi) at least one further active ingredient.

[0105] The solid fast dissolving combination in the form of a mixture of powders and / or granules of the invention may be present in a solid composition which comprises an aforementioned component (I) to (ill) as above defined, and optionally, (iv) at least one flavour and / or colorant and / or sweetener and / or oils (lipids) and / or surfactants and / or a carrier or at least one excipient of pharmaceutical or food grade; and / or (v) at least a pH adjusting agent, preferably an organic acid; more preferably at least one hydroxy acid, e.g., citric acid and / or tartaric acid; and / or (vi) at least one further active ingredient, wherein said solid composition is useful for the preparation, for example, of ready to drink (RTD) beverage or another water-based fluid product for oral administration containing HMW-HA.

[0106] The solid fast dissolving combination in the form of a mixture of powders and / or granules of the invention may be present in a solid composition which comprises an aforementioned component (I) to (ill) as above defined, and optionally, (iv) at least one flavour and / or colorant and / or sweetener and / or oils (lipids) and / or surfactants and / or a carrier or at least one excipient of pharmaceutical or food grade; and / or (v) at least a pH adjusting agent, preferably an organic acid; more preferably at least one hydroxy acid, e.g., citric acid and / or tartaric acid; and / or (vi) at least one further active ingredient, wherein said solid composition is useful for the preparation of a water-based HMW- HA spray product (e.g., a mouth spray, a topical spray for the skin or joints, a lung spray).

[0107] Even if not expressly disclosed, the term "composition” herein includes pharmaceutical, nutraceutical or food compositions or compositions for medical devices under the EU Reg. 745 / 2017.

[0108] Preferably, flavours and / or colorants and / or sweeteners may be of synthetic or natural origin. Preferably, components (iv) may be selected from fruit flavours, such as vanilla, orange, blueberry, lemon, and the like; and sweeteners such as sucralose and / or stevia and / or erythritol. Other sugars, sugar alcohols, sweeteners can be used in the solid combination (or composition) of the present invention, e.g. fructose, glucose, isomaltulose, allulose, stevia, sucralose, isomalt, maltitol, mannitol, sorbitol, lactitol, trehalose, tagatose, xylitol etc.

[0109] Colorants may be any colorant which makes the more appealing the composition when mixed up with water, for instance yellow colorants, such as vanilla yellow and the like.

[0110] Colorants may also be selected from active-coloured ingredients.

[0111] Preferably, said (vi) at least one further active ingredient can be selected from the following ingredients:

[0112] Acmella oleracea

[0113] Andrographis paniculata

[0114] Ashwagandha

[0115] Chondroitin sulfate (e.g. Chondroitin, Greendroitin®, Vivatis Pharma)

[0116] Boswellia serrata or Boswellia serrata extract (e.g. from Olene Life Science)

[0117] Collagen hydrolysates (e.g. Type I, II, III, V, and X)

[0118] Curcumin (e.g. Turmacin, Natural Remedies or TurmXtra 60N, Nutriventia) or CurcuWIN, Omniactive

[0119] Dermatan sulfate

[0120] Eggshell membrane

[0121] Ginger (e.g. Gingever, Omniactive)

[0122] Glucosamine, Glucosamine salts, N-Acetyl Glucosamine

[0123] Methylsulfonyl methane

[0124] Olive Extract (containing Oleuropein, Polyphenols and or Hydroxy Tyrosol)

[0125] Omega-3 (e.g. Eicosapentaenoic acid and docosahexaenoic acid)

[0126] Palmitoylethanolamide (Levagen+, Gencor)

[0127] Tamarindus indica seed

[0128] Hydroxytyrosol

[0129] Vitamins (e.g. Vitamin C)

[0130] Water soluble Vitamins (e.g. B- vitamins, water soluble Vitamin E)

[0131] Zingiber officinale or mixture thereof; preferably when the solid combination or composition is intended for joint health.

[0132] Combinations of two or more of the above ingredients are also possible.

[0133] Preferably, said (vi) at least one further active ingredient can be selected from ingredients:

[0134] Astaxanthin (Xanthin, Valensa)

[0135] Collagen hydrolysates ((e.g. Type I, II, III, V, and X)

[0136] Coenzyme Q10

[0137] Glucosamine, Glucosamine salts, N-Acetyl Glucosamine

[0138] Grapeseed Extract (Proanthocyanidin rich)

[0139] Hesperidin, Narirutin, Vitamin C (Red orange complex, Bionap)

[0140] Olive Extract (containing Oleuropein, Polyphenols (Bonolive, Bionap) and or Hydroxy Tyrosol) Luteolin-7-o-glucosid und 30% Ortho-Diphenols from Pharmactive

[0141] Hydroxytyrosol (Hytolive, Genosa)

[0142] Lactoferrin

[0143] Minerals (e.g. Selenium, Zinc, Copper)

[0144] Oleuropein (Oleocol, Bioactor)

[0145] Omega-3

[0146] Oputia sativea and Opuntia Ficus Indica Flower (= Anthocyanins (Cyanidin-3-Glucoside), lsorhamnetin-3- Rutinoside (Actrisave, Bionap)

[0147] Polyphenols (SELECTSIEVE® Apple, Roelmi)

[0148] Resveratrol (Resverafen, Akay; Veri-Sperse® (t-Resveratrol CWD 90), Gencor)

[0149] Spermidin (Soybean extract, Bionap)

[0150] Vitamins (e.g. Vitamin C powder, encapsultated (C-Fence, Nutriventia), Vitamin E, Tocotrienols,)

[0151] Water soluble Vitamins (e.g. B- vitamins, water soluble Vitamin E) or mixture thereof; preferably when the solid combination or composition is intended for skin health and / or antiaging.

[0152] Combinations of two or more of the above ingredients are also possible.

[0153] All the components used in the solid combination and composition of the present invention are physiologically acceptable, having a food or pharmaceutical grade.

[0154] All the components of the solid fast dissolving composition of the present invention are in a powder form and / or in a granular form, to give a solid fast dissolving composition of the present invention in the form of a mixture of powders and / or granules.

[0155] For example, the powder can be transferred into a stick pack or a can or a cardboard wrap box.

[0156] Preferably, the fast-dissolving solid combination (or composition) according to the invention does not comprise carboxymethylcellulose (CMC), nor carboxymethylcellulose sodium, which are usually used as thickening agent and stabilizers.

[0157] In addition, preferably, the fast-dissolving solid combination (or composition) according to the invention does not comprise thickening agents and / or stabilizers, nor carboxymethylcellulose (CMC) and carboxymethylcellulose sodium. This is because the purpose of the present invention is to obtain a liquid composition RTD, and not a gel. According to the invention, said at least one dissolving aid component selected from group comprising or, alternatively, consisting of:

[0158] (i) an effervescent system that comprises at least one basic substance which is selected from carbonate or bicarbonate, and at least one acid substance which is selected from citric or tartaric acid, and mixtures thereof;

[0159] (ii) at least one water-soluble salt which is selected from a water-soluble alkali-metal citrate salt, a water-soluble alkali-metal gluconate salt, a water-soluble alkali-earth metal citrate salt, a water-soluble alkali-earth metal gluconate salt, and mixtures thereof;

[0160] (iii) at least one sugar which is selected from sucrose, lactose, maltose, trehalose, erythritol, xylitol, maltitol, sorbitol, mannitol, or mixtures thereof; Is used for preparing a fast dissolving powder composition comprising a high molecular weight hyaluronic acid (HM W-HA) having an average molecular weight equal to or bigger than 1 ,000 kDa.

[0161] According to one of its aspects, the subject matter of the present invention relates to a process for preparing an HMW-HA water-based fluid composition, e.g. a drinkable composition for oral use or a spray product for topical use, comprising the steps of: a) putting into contact a solid fast dissolving composition of the invention with a water-based fluid, which is selected from the group comprising or, alternatively, consisting of water, a beverage, a milk, a milk substitute, a plant-based milk, non dairy substitute, non-dairy beverage, instant milk; non-alcoholic, alcoholic, a fruit drink, energy drink, fortified drink, herbal drink, sport drink, yogurt drink, buttermilk drink, probiotic drink, a nectar, a juice or a cappuccino, a smoothie, a coffee, a macchiato, a cafe au lait, a coffee milk, a frapuccino, an espresso, an espresso macchiato, a latte espresso, a flat white, a caffee latte, a cacao, or mixtures thereof; b) mixing, preferably with the aid of a spoon, for a time from 10 seconds to 5 minutes, preferably from 1 minute to 3 minutes, at a temperature comprised from 18 °C to 40°C, preferably comprised from 18°C to 25 °C, to obtain said HMW-HA water-based fluid composition.

[0162] The resulting fluid (e.g. water and the HMW-HA combination or composition of the present invention) can be also used for a spray application (for the mouth, as a lung spray, for the intact skin, for the wounded skin, for the knees). Object of the present invention is also a HMW-HA water-based fluid composition which is obtained by the process described above.

[0163] Preferably, the HMW-HA water-based fluid composition obtainable or obtained by the process above described is for oral use, preferably is drinkable composition for oral use, or is for topical use, preferably is a spray product for topical use.

[0164] Preferably, said spray product, preferably a water-based HMW-HA spray product for topical use is selected from the group comprising or, alternatively, consisting of mouth spray, topical spray for the skin or joints, lung spray.

[0165] If desired, it is possible to use the above-mentioned ingredients for an industrial production of an HMW-HA containing beverage composition. In this case, the components of the HMW-HA combination or composition of the present invention can be mixed, stirred with an industrial mixer (Krieger, Becomix) and filled into glass bottles, shots, or in plastic containers / bottles. Due to the innovative ingredients for the dissolving process the filling times of the containers (bottles) can be reduced if industrial mixers are used (compared to dissolve an HMW-HA alone in liquids like water, milks etc.).

[0166] For example, a shot can contain an HMW-HA combination or composition of the present invention including also has vitamins, minerals, collagen, aloe vera gel, polyphenols.

[0167] Preferably, the solid fast dissolving composition in the form of a mixture of powders and / or granules of the invention comprises or, alternatively, consists of:

[0168] (A) HMW-HA and an effervescent system as defined above; more preferably, wherein said an effervescent system consists of a bicarbonate salt and citric acid or tartaric acid; even more preferably, wherein said an effervescent system consists of sodium hydrogen carbonate and anhydrous citric acid; or

[0169] (B) HMW-HA and at least one water-soluble salt as defined above; more preferably, wherein said at least one water-soluble salt is selected from a water-soluble alkali-metal citrate and / or gluconate salt and / or a water soluble alkali-earth metal citrate and / or gluconate salt and / or mixtures thereof; even more preferably, wherein said at least one water-soluble salt is selected from tripotassium citrate, tripotassium citrate monohydrate, potassium gluconate, sodium gluconate, or mixtures thereof; or

[0170] (C) HMW-HA and at least one sugar as defined above; more preferably, wherein said at least one sugar is selected from a disaccharide, a sugar alcohol or mixtures thereof; even more preferably, wherein said at least one sugar is selected from sucrose, erythritol, xylitol, maltitol, or mixtures thereof; or

[0171] (D) HMW-HA, an effervescent system as defined above and at least one water-soluble salt as defined above; more preferably, wherein said an effervescent system consists of a bicarbonate salt and citric acid or tartaric acid and said at least one water-soluble salt is selected from a water-soluble alkali-metal citrate and / or gluconate salt and / or a water soluble alkali-earth metal citrate and / or gluconate salt and / or mixtures thereof; even more preferably, wherein said an effervescent system consists of sodium hydrogen carbonate and anhydrous citric acid and said at least one water-soluble salt is selected from tripotassium citrate, tripotassium citrate monohydrate, potassium gluconate, sodium gluconate, or mixtures thereof; or

[0172] (E) HMW-HA an effervescent system as defined above and at least one sugar as defined above; more preferably, wherein said an effervescent system consists of a bicarbonate salt and citric acid or tartaric acid and said at least one sugar is selected from a disaccharide, a sugar alcohol or mixtures thereof; even more preferably, wherein said an effervescent system consists of sodium hydrogen carbonate and anhydrous citric acid and said at least one sugar is selected from sucrose, erythritol, xylitol, maltitol, or mixtures thereof; or

[0173] (F) HMW-HA, an effervescent system as defined above and an acacia gum as defined above; more preferably, wherein said an effervescent system consists of a bicarbonate salt and citric acid or tartaric acid; even more preferably, wherein said an effervescent system consists of sodium hydrogen carbonate and anhydrous citric acid; or

[0174] (G) HMW-HA, at least one water-soluble salt as defined above and at least one sugar as defined above; more preferably, wherein said at least one water-soluble salt is selected from a water-soluble alkali-metal citrate and / or gluconate salt and / or a water soluble alkali-earth metal citrate and / or gluconate salt and / or mixtures thereof; even more preferably, wherein said at least one water-soluble salt is selected from tripotassium citrate, tripotassium citrate monohydrate, potassium gluconate, sodium gluconate, or mixtures thereof and said at least one sugar is selected from sucrose, erythritol, xylitol, maltitol, or mixtures thereof; or

[0175] (H) HMW-HA, at least one water-soluble salt as defined above and an acacia gum as defined above; more preferably, wherein said at least one water-soluble salt is selected from a water-soluble alkali-metal citrate and / or gluconate salt and / or a water soluble alkali-earth metal citrate and / or gluconate salt and / or mixtures thereof; even more preferably, wherein said at least one water-soluble salt is selected from tripotassium citrate, tripotassium citrate monohydrate, potassium gluconate, sodium gluconate, or mixtures thereof; or

[0176] (I) HMW-HA, at least one sugar as defined above and an acacia gum as defined above; more preferably, wherein said at least one sugar is selected from a disaccharide, a sugar alcohol or mixtures thereof; even more preferably, wherein said at least one sugar is selected from sucrose, erythritol, xylitol, maltitol, or mixtures thereof; or

[0177] (L) HMW-HA, an effervescent system as defined above, at least one water-soluble salt as defined above and at least one sugar as defined above; more preferably, wherein said an effervescent system consists of a bicarbonate salt and citric acid or tartaric acid; said at least one water-soluble salt is selected from a water- soluble alkali-metal citrate and / or gluconate salt and / or a water soluble alkali-earth metal citrate and / or gluconate salt and / or mixtures thereof; and said at least one sugar is selected from a disaccharide, a sugar alcohol or mixtures thereof; even more preferably, wherein said an effervescent system consists of sodium hydrogen carbonate and anhydrous citric acid; said at least one water-soluble salt is selected from tripotassium citrate, tripotassium citrate monohydrate, potassium gluconate, sodium gluconate, or mixtures thereof; and said at least one sugar is selected from sucrose, erythritol, xylitol, maltitol, or mixtures thereof; or

[0178] (M) HMW-HA, an effervescent system as defined above, at least one water-soluble salt as defined above and an acacia gum as defined above; more preferably, wherein said an effervescent system consists of a bicarbonate salt and citric acid or tartaric acid and said at least one water-soluble salt is selected from a water- soluble alkali-metal citrate and / or gluconate salt and / or a water soluble alkali-earth metal citrate and / or gluconate salt and / or mixtures thereof; even more preferably, wherein said an effervescent system consists of sodium hydrogen carbonate and anhydrous citric acid and said at least one water-soluble salt is selected from tripotassium citrate, tripotassium citrate monohydrate, potassium gluconate, sodium gluconate, or mixtures thereof; or

[0179] (N) HMW-HA, an effervescent system as defined above, at least one sugar as defined above and an acacia gum as defined above; more preferably, wherein said an effervescent system consists of a bicarbonate salt and citric acid or tartaric acid and said at least one sugar is selected from a disaccharide, a sugar alcohol or mixtures thereof; even more preferably, wherein said an effervescent system consists of sodium hydrogen carbonate and anhydrous citric acid and said at least one sugar is selected from sucrose, erythritol, xylitol, maltitol, or mixtures thereof; or

[0180] (O) HMW-HA, at least one water-soluble salt as defined above, at least one sugar as defined above and an acacia gum as defined above; more preferably, wherein said at least one water-soluble salt is selected from a water-soluble alkali-metal citrate and / or gluconate salt and / or a water soluble alkali-earth metal citrate and / or gluconate salt and / or mixtures thereof and said at least one sugar is selected from a disaccharide, a sugar alcohol or mixtures thereof; even more preferably, wherein said at least one water-soluble salt is selected from tripotassium citrate, tripotassium citrate monohydrate, potassium gluconate, sodium gluconate, or mixtures thereof and said at least one sugar is selected from sucrose, erythritol, xylitol, maltitol, or mixtures thereof; or

[0181] (P) HMW-HA, an effervescent system as defined above, at least one water-soluble salt as defined above, at least one sugar as defined above and an acacia gum as defined above; more preferably, wherein said an effervescent system consists of a bicarbonate salt and citric acid or tartaric acid; said at least one water-soluble salt is selected from a water-soluble alkali-metal citrate and / or gluconate salt and / or a water soluble alkali- earth metal citrate and / or gluconate salt and / or mixtures thereof; and said at least one sugar is selected from a disaccharide, a sugar alcohol or mixtures thereof; even more preferably, wherein said an effervescent system consists of sodium hydrogen carbonate and anhydrous citric acid; said at least one water-soluble salt is selected from tripotassium citrate, tripotassium citrate monohydrate, potassium gluconate, sodium gluconate, or mixtures thereof; and said at least one sugar is selected from sucrose, erythritol, xylitol, maltitol, or mixtures thereof; or

[0182] (Q) any one of the above compositions from (A) to (P) in combination with one or more flavours and / or colorants and / or sweetener and / or pH adjusting agents, preferably a hydroxy acid, even more preferably citric acid and / or tartaric acid, and / or surfactants and / or actives as defined above.

[0183] Preferably, when an effervescent system is present, the weight ratio HMW-HA / effervescent system is the range comprised from 0.02 to 0.8, more preferably in the range comprised from 0.08 to 0.6, wherein said an effervescent system preferably consists of a bicarbonate salt, e.g., sodium hydrogen carbonate, and citric acid, e.g., anhydrous citric acid, or tartaric acid.

[0184] Preferably, when at least one water soluble salt is present, the weight ratio HMW-HA / water soluble salt is the range comprised from 0.02 to 0.3, more preferably in the range comprised from 0.04 to 0.2, wherein said at least one water soluble salt preferably is selected from a water-soluble alkali-metal citrate and / or gluconate salt and / or a water soluble alkali-earth metal citrate and / or gluconate salt and / or mixtures thereof, more preferably is selected from tripotassium citrate, tripotassium citrate monohydrate, potassium gluconate, sodium gluconate, or mixtures thereof.

[0185] Preferably, when at least one sugar is present, the weight ratio HMW-HA / sugar is the range comprised from 0.02 to 0.2, more preferably in the range comprised from 0.04 to 0.1 , wherein said at least one sugar preferably is selected from a disaccharide, e.g. sucrose, a sugar alcohol, e.g. erythritol, xylitol, maltitol, or mixtures thereof; more preferably is selected from sucrose, maltitol, erythritol, xylitol or mixtures thereof .

[0186] Preferably, when at least an acacia gum is present, the weight ratio HMW-HA / acacia gum is the range comprised from 0.05 to 0.5, more preferably in the range comprised from 0.1 to 0.3.

[0187] It was observed that the above compositions showed a faster dissolution in water, less or no lump formation, a better flow behaviour from a beverage drinking glass to the mouth, a better mouthfeel, an improved viscosity when mixed with water, contrary to the extreme high viscosity and poor dissolution behaviour of HMW-HA alone in a liquid, preferably but not limited to, water.

[0188] For example, Greenluronic® powder by Vivatis Pharma company (high molecular weight hyaluronic acid of fungal (Tremella fuciformis) origin, with MW 1 ,500-4,000 kDa) has poor dissolution behaviour in water. It dissolves only partially, with lumps formation, with the aid of a spoon and it forms a very stiff hydrogel with the aid of an industrial mixer (as shown in Fig. 1A and Fig. 1 B). The fast-dissolving solid combinations or compositions of Greenluronic® according to the present invention show a very good dissolution behaviour in water, even with the only aid of a spoon (as shown in Fig. 2, 3A and 3B).

[0189] The compositions of the invention can be easily used by the consumers at home. Indeed, a consumer may just use a spoon as "stirrer”, which is sufficient to make the HMW-HA more fluid thanks to the further components of the composition. An alternative to a spoon is a small handheld electric mixer. If a consumer has a problem to dissolve the HMW-HA composition the company selling the HMW-HA composition should give the advice to use a milk foamed, manual model or handheld stick brothers (e.g., Milchaufschaumer FINO, rotation speed 12.000 U / Min, Artikel-Nr.: 12720, GEFU GmbH, Braukweg 28, 59889 Eslohe, Germany). On the other hand, in industrial processes, a typical industrial stirrer can be used.

[0190] The fluid (e.g. water and the HMW-HA combination or composition of the present invention) can also be advantageously used for the preparation of a water-based HMW-HA spray product (e.g., a mouth spray, a topical spray for the skin or joints, a lung spray).

[0191] According to one its aspects, the present invention relates to an instant or RTD (ready to drink) or drinkable beverage composition obtained from fast dissolving in a fluid, preferably a water-based fluid, a solid fast dissolving HMW-HA combination or composition in the form of a mixture of powders and / or granules of the present invention. According to one its aspects, the present invention relates to a fluid (e.g. water and the HMW-HA combination or composition of the present invention) obtained from fast dissolving in a fluid, preferably a water-based fluid, a solid fast dissolving HMW-HA combination or composition in the form of a mixture of powders and / or granules of the present invention that can be used for a spray application (for the mouth, as a lung spray, for the intact skin, for the wounded skin, for the knees).

[0192] According to one its aspects, the present invention relates to the solid fast dissolving combination or composition in the form of a mixture of powders and / or granules or drinkable composition or fluid composition for oral use obtained therefrom, or a fluid composition as a spray for topical use obtained therefrom, for use in a method for managing joint diseases and / or disorders and / or supporting joint health and / or supporting skin health and / or counteracting aging and / or managing oral cavity diseases and / or disorders and / or managing lung diseases and / or disorders and / or supporting oral cavity or lung health in a subject in need.

[0193] Preferably, said oral cavity diseases and / or disorders that can be treated and / or prevented using a fluid composition as a spray for topical use, obtained from fast dissolving in a fluid, preferably a water-based fluid, a solid fast dissolving HMW-HA combination or composition in the form of a mixture of powders and / or granules of the present invention, are selected from periodontitis, oral lichen planus, oral ulcer, oral wound, pain of the oral mucosa after biopsy, gingivitis, oral mucositis.

[0194] Preferably, the fast dissolving HMW-HA powder composition according to the invention or the drinkable HMW-HA water-based liquid composition described above, or a water-based HMW-HA spray product above described are preferably used in a method for the treatment of joint diseases, and osteoarthritic or osteoarthritis diseases, for supporting joint health, or for supporting skin health or derma health, or for counteracting skin aging, or for a glowing skin, or for moisturised and supple skin, or for the treatment of oral cavity diseases, lung diseases, for supporting oral cavity health, or supporting lung health in a subject in need.

[0195] Object of the present invention is also the non-therapeutic use of said fast dissolving HMW-HA powder composition or of the drinkable HMW-HA water-based fluid composition or of the water-based HMW-HA spray product, preferably for supporting joint health, or for supporting skin health or derma health, or for counteracting skin aging, or for a glowing skin, or for moisturised and supple skin, or for supporting oral cavity health, or supporting lung health. Preferred embodiments (FRn) of the present invention are herewith report.

[0196] FR1 . A solid fast dissolving composition comprising or, alternatively, consisting of high molecular weight hyaluronic acid (HM W-HA) having an average molecular weight equal to or bigger than 1 ,000 kDa in combination with at least one dissolving aid component which is selected from group comprising or, alternatively, consisting of:

[0197] I. an effervescent system that comprises at least one basic substance which is selected from carbonate or bicarbonate, and at least one acid substance which is selected from citric or tartaric acid, and mixtures thereof; ii. at least one water-soluble salt which is selected from a water-soluble alkali-metal citrate salt, a water-soluble alkali-metal gluconate salt, a water-soluble alkali-earth metal citrate salt, a water-soluble alkali-earth metal gluconate salt, and mixtures thereof; iii. at least one sugar which is selected from sucrose, lactose, maltose, trehalose, erythritol, xylitol, maltitol, sorbitol, mannitol, or mixtures thereof; wherein said solid fast dissolving composition is in the form of a mixture of powders and / or granules.

[0198] FR2. The solid fast dissolving HMW-HA composition according to FR1 , wherein said high molecular weight hyaluronic acid (HMW-HA) has an average molecular weight comprised from 1 ,000 kDa to 10,000 kDa; preferably, it has a molecular weight comprised from 1 ,000 kDa to 8,000 kDa, more preferably, it has a molecular weight comprised from 1 ,000 to 7,000 kDa, even more preferably, it has a molecular weight comprised from 1 ,000 kDa to 6,000 kDa.

[0199] FR3. The solid fast dissolving HMW-HA composition according to FR1 or FR2, wherein said (I) an effervescent system comprises or, alternatively, consists of at least one basic substance capable of releasing carbon dioxide in the presence of at least one acidic substance, wherein said basic substance is preferably selected from carbonate or bicarbonate salts; more preferably, sodium and / or potassium carbonate, sodium and / or potassium bicarbonate, or mixtures thereof; and said at least one acidic substance is preferably selected from organic acids; more preferably a hydroxy acids, such as citric acid and / or tartaric acid.

[0200] FR4. The solid fast dissolving HMW-HA composition according to anyone of FR 1-3, wherein said (II) at least one water-soluble salt is preferably selected from the group comprising or, alternatively, consisting of a water-soluble alkali-metal citrate salt, a water-soluble alkali-metal gluconate salt, a water soluble alkali-earth metal citrate salt, a water soluble alkali-earth metal gluconate salt, and mixture thereof; more preferably, tripotassium citrate, tripotassium citrate monohydrate, potassium gluconate, sodium gluconate, and mixtures thereof.

[0201] FR5. The solid fast dissolving HMW-HA composition according to any one of FR1-4, wherein said (iii) at least one sugar is preferably selected from the group comprising or, alternatively, consisting of sucrose, maltitol, erythritol, xylitol or mixtures thereof.

[0202] FR6. The solid fast dissolving HMW-HA composition according to anyone FR1-5, wherein said composition further comprises:

[0203] - at least one flavour and / or colorant and / or sweetener and / or surfactants and / or a carrier and / or at least one excipient of pharmaceutical or food grade; and / or

[0204] - at least a pH adjusting agent, preferably an organic acid; more preferably at least one hydroxy acid, e.g., citric acid and / or tartaric acid and / or mixture thereof; and / or - at least one further active ingredient.

[0205] FR7. The solid fast dissolving HMW-HA combination or composition according to any one of FR1-6, wherein said combination or composition comprises or, alternatively, consists of HMW-HA and (i) an effervescent system, and (ii) at least one water-soluble salt and / or (iii) at least one sugar, and an acacia gum.

[0206] FR8. A process for preparing an HMW-HA water-based fluid composition, wherein said process comprises: a) putting into contact a solid fast dissolving composition according to anyone of FR1-7 with a water-based fluid which is selected from water, milk, plant-based milk, fruit drink, energy drink, fortified drink, herbal drink, sport drink, yogurt drink, buttermilk drink, probiotic drink, a nectar, a juice or cappuccino, smoothie, coffee, cafe au lait, coffee milk, cacao, or mixtures thereof, to obtain a product; b) mixing said product for a time comprised from 5 seconds to 5 minutes, preferably from 30 seconds to 3 minutes, at a temperature from 18 °C to 40°C, preferably from 18°C to 25 °C, to obtain said HMW-HA water-based fluid composition.

[0207] FR9. The process for preparing an HMW-HA water-based fluid composition according to FR8, wherein said composition is drinkable composition for oral use or is spray product for topical use.

[0208] FR10. An HMW-HA water-based fluid composition which is obtained by the process according to FR8.

[0209] FR11 . A drinkable HMW-HA water-based fluid composition for oral use which is obtained by the process according to FR8 and FR9.

[0210] FR12. A water-based HMW-HA spray product for topical use which is obtained by the process according to FR8 and FR9.

[0211] FR13. The water-based HMW-HA spray product for topical use according to FR12, wherein said product is selected from mouth spray, topical spray for the skin or joints, lung spray.

[0212] FR14. A solid fast dissolving HMW-HA composition according to any one of FR1-7, or a drinkable HMW-HA waterbased fluid composition according to FR11 , or a water-based HMW-HA spray product according to FR12 or FR13, for use in a method for the treatment of joint diseases, for supporting joint health, or for supporting skin health, or for counteracting skin aging, or for the treatment of oral cavity diseases, lung diseases, for supporting oral cavity health, or supporting lung health in a subject in need.

[0213] FR15. A non-therapeutic use of a solid fast dissolving HMW-HA composition according to any one of FR1-7, or a drinkable HMW-HA water-based fluid composition according to FR11 , or a water-based HMW-HA spray product according to FR12 or FR13, for use for supporting joint health, or for supporting skin health, or for counteracting skin aging, or for supporting oral cavity health, or supporting lung health.

[0214] FR16. Use of at least one dissolving aid component which is selected from group comprising or, alternatively, consisting of: i. an effervescent system that comprises at least one basic substance which is selected from carbonate or bicarbonate, and at least one acid substance which is selected from citric or tartaric acid, and mixtures thereof; ii. at least one water-soluble salt which is selected from a water-soluble alkali-metal citrate salt, a water-soluble alkali-metal gluconate salt, a water-soluble alkali-earth metal citrate salt, a water-soluble alkali-earth metal gluconate salt, and mixtures thereof; ill. at least one sugar which is selected from sucrose, lactose, maltose, trehalose, erythritol, xylitol, maltitol, sorbitol, mannitol, or mixtures thereof; for preparing a solid fast dissolving composition comprising a high molecular weight hyaluronic acid (HMW-HA) having an average molecular weight equal to or bigger than 1 ,000 kDa, wherein said solid fast dissolving composition is in the form of a mixture of powders and / or granules.

[0215] Representative examples of the solid fast dissolving compositions in the form of a mixture of powders and / or granules and water-based fluid compositions obtained therefrom of the invention are reported in the Experimental Section which follows, for illustrative purposes only.

[0216] Other preferred embodiments (En) of the present invention are herewith report.

[0217] E1 . A fast dissolving powder composition comprising or, alternatively, consisting of high molecular weight hyaluronic acid (HMW-HA) having an average molecular weight equal to or bigger than 1 ,000 kDa in combination with at least one dissolving aid component which is selected from the group comprising or, alternatively, consisting of:

[0218] (i) an effervescent system that comprises at least one basic substance which is selected from carbonate or bicarbonate, and at least one acid substance which is selected from citric or tartaric acid, and mixtures thereof;

[0219] (ii) at least one water-soluble salt which is selected from a water-soluble alkali-metal citrate salt, a water- soluble alkali-metal gluconate salt, a water-soluble alkali-earth metal citrate salt, a water-soluble alkali-earth metal gluconate salt, and mixtures thereof.

[0220] E2. The fast dissolving HMW-HA composition according to E1 , wherein said at least one dissolving aid component is selected from (iii) at least one sugar which is selected from the group comprising or, alternatively, consisting of sucrose, lactose, maltose, trehalose, erythritol, xylitol, maltitol, sorbitol, mannitol, or mixtures thereof.

[0221] E3. The fast dissolving HMW-HA composition according to E1 or E2, wherein said high molecular weight hyaluronic acid (HMW-HA) has an average molecular weight comprised from 1 ,000 kDa to 10,000 kDa; preferably, it has a molecular weight comprised from 1 ,000 kDa to 8,000 kDa, more preferably, it has a molecular weight comprised from 1 ,000 to 7,000 kDa, even more preferably, it has a molecular weight comprised from 1 ,000 kDa to 6,000 kDa. E4. The fast dissolving HMW-HA composition according to anyone of E1-E3, wherein said high molecular weight hyaluronic acid (HMW-HA) has an average molecular weight comprised from 1 ,500 kDa to 4,000 kDa.

[0222] E5. The fast dissolving HMW-HA composition according to anyone of E1-E4, wherein said (i) an effervescent system comprises or, alternatively, consists of at least one basic substance capable of releasing carbon dioxide in the presence of at least one acidic substance, wherein said basic substance is preferably selected from the group comprising or, alternatively, consisting of carbonate or bicarbonate salts; more preferably, sodium and / or potassium carbonate, sodium and / or potassium bicarbonate, or mixtures thereof; and said at least one acidic substance is preferably selected from the group comprising or, alternatively, consisting of organic acids; more preferably a hydroxy acids, even more preferably citric acid and / or tartaric acid. E6. The fast dissolving HMW-HA composition according to anyone of E1-E5, wherein said (ii) at least one water- soluble salt is preferably selected from the group comprising or, alternatively, consisting of a water-soluble alkali- metal citrate salt, a water-soluble alkali-metal gluconate salt, a water soluble alkali-earth metal citrate salt, a water soluble alkali-earth metal gluconate salt, and mixture thereof; more preferably, tripotassium citrate, tripotassium citrate monohydrate, potassium gluconate, sodium gluconate, and mixtures thereof.

[0223] E7. The fast dissolving HMW-HA composition according to anyone of E1-E6, wherein said (iii) at least one sugar is preferably selected from the group comprising or, alternatively, consisting of sucrose, maltitol, erythritol, xylitol or mixtures thereof.

[0224] E8. The fast dissolving HMW-HA composition according to anyone of E1-E7, wherein said composition further comprises:

[0225] - at least one flavour and / or colorant and / or sweetener and / or surfactants and / or a carrier and / or at least one excipient of pharmaceutical or food grade; and / or

[0226] - at least a pH adjusting agent, preferably an organic acid; more preferably at least one hydroxy acid, even more preferably citric acid and / or tartaric acid and / or mixture thereof; and / or

[0227] - at least one further active ingredient.

[0228] E9. The fast dissolving HMW-HA combination or composition according to anyone of E1-E8, wherein said combination or composition comprises or, alternatively, consists of HMW-HA and (I) an effervescent system, and (II) at least one water-soluble salt and / or (iii) at least one sugar, and an acacia gum.

[0229] E10. A process for preparing an HMW-HA water-based fluid composition, wherein said process comprises: a) putting into contact a fast dissolving composition according to anyone of E1-E9 with a water-based fluid which is selected from the group comprising or, alternatively, consisting of water, milk, plant-based milk, fruit drink, energy drink, fortified drink, herbal drink, sport drink, yogurt drink, buttermilk drink, probiotic drink, a nectar, a juice or cappuccino, smoothie, coffee, cafe au lait, coffee milk, cacao, or mixtures thereof, to obtain a product; b) mixing said product for a time comprised from 5 seconds to 5 minutes, preferably from 30 seconds to 3 minutes, at a temperature comprised from 18 °C to 40°C, preferably comprised from 18°C to 25 °C, to obtain said HMW- HA water-based fluid composition.

[0230] E11. The process for preparing an HMW-HA water-based fluid composition according to E10, wherein said composition is for oral use, preferably is drinkable composition for oral use, or is for topical use, preferably is a spray product for topical use.

[0231] E12. An HMW-HA water-based fluid composition which is obtained by the process according to E10.

[0232] E13. A drinkable HMW-HA water-based fluid composition for oral use which is obtained by the process according to E10 and E11.

[0233] E14. A water-based HMW-HA product for topical use, preferably a spray product for topical use which is obtained by the process according to E10 and E11 .

[0234] E15. The water-based HMW-HA spray product for topical use according to E14, wherein said product is selected from the group comprising or, alternatively, consisting of mouth spray, topical spray for the skin or joints, lung spray. E16. A fast dissolving HMW-HA powder composition according to any one of E1-E9, or a drinkable HMW-HA water- based fluid composition according to E13, or a water-based HMW-HA spray product according to E14 or E15, for use in a method for the treatment of joint diseases, and osteoarthritic or osteoarthritis diseases, for supporting joint health, or for supporting skin health or derma health, or for counteracting skin aging, or for a glowing skin, or for moisturised and supple skin, or for the treatment of oral cavity diseases, lung diseases, for supporting oral cavity health, or supporting lung health in a subject in need.

[0235] E17. A non-therapeutic use of a fast dissolving HMW-HA powder composition according to any one of E1-E9, or a drinkable HMW-HA water-based fluid composition according to E13, or a water-based HMW-HA spray product according to E14 or E15, for use for supporting joint health, or for supporting skin health or derma health, or for counteracting skin aging, or for a glowing skin, or for moisturised and supple skin, or for supporting oral cavity health, or supporting lung health.

[0236] E18. Use of at least one dissolving aid component which is selected from group comprising or, alternatively, consisting of:

[0237] (I) an effervescent system that comprises at least one basic substance which is selected from carbonate or bicarbonate, and at least one acid substance which is selected from citric or tartaric acid, and mixtures thereof;

[0238] (ii) at least one water-soluble salt which is selected from a water-soluble alkali-metal citrate salt, a water- soluble alkali-metal gluconate salt, a water-soluble alkali-earth metal citrate salt, a water-soluble alkali-earth metal gluconate salt, and mixtures thereof;

[0239] (ill) at least one sugar which is selected from sucrose, lactose, maltose, trehalose, erythritol, xylitol, maltitol, sorbitol, mannitol, or mixtures thereof; for preparing a fast dissolving powder composition comprising a high molecular weight hyaluronic acid (HMW-HA) having an average molecular weight equal to or bigger than 1 ,000 kDa.

[0240] The following are representative practical examples.

[0241] EXPERIMENTAL SECTION

[0242] Examples of compositions

[0243] Representative Examples of solid fast dissolving compositions of the invention mixed with water up to 100 g.

[0244] They are powders to obtain aqueous solution or fine suspension, e.g., powder to obtain fluid drink formulation. Consumers can use these powders to make their own beverages.

[0245] The dissolution behaviour of the compositions of the present Examples was observed. The compositions were stirred with a spoon without a lab mixer or the usage of an industrial mixer.

[0246] In Examples 1-5 an effervescent system is used as dissolving aid. The pH can be adjusted to the desired level.

[0247] In Examples 6, sugar is used as dissolving aid.

[0248] In Examples 7-10, a water-soluble salt is used as dissolving aid.

[0249] In Example 10, instead of Greenluronic®, a classical hyaluronic acid with high molecular weight (Sodium Hyaluronate with MW 1 ,800-2,200 kDa) (Exception HYAL HW (1 ,800-2,200) from the company Roelmi was used. In Examples 11-12, a water-soluble salt and a hydroxy acid are used as dissolving aid. In Example 13, a water-soluble salt, a sugar alcohol and a hydroxy acid are used as dissolving aid.

[0250] Example 14 is an example of a composition comprising an effervescent system and a water-soluble salt as dissolving aid and further comprising an acacia gum, a sweetener, a flavor and a further active ingredient (e.g. for joint health, Chondroitin sulfate, Greendroitin®, Vivatis) In Example 15 a combination of two water soluble salt is used as dissolving aids.

[0251] In Example 16 a sugar alcohol is used as a dissolving aid.

[0252] In Example 17 a combination of two water soluble salts is used as a dissolving aid and a color ingredient was used.

[0253] Example 1 Table 1

[0254] A powder mixture of Greenluronic, Sodium hydrogen carbonate, anhydrous Citric acid was mixed, and this powder mixture was poured into water.

[0255] Result: fast dissolving process a liquid formulation is obtained (small particles in the beginning). pH: 3.92 (25°C). Example 2 Citronensaure wasserfrei F6000

[0256] Table 2

[0257] A powder mixture of Greenluronic, Sodium hydrogen carbonate, anhydrous Citric acid was mixed, and this powder mixture was poured into water.

[0258] Result: fast dissolving process, a liquid formulation is obtained immediately (small particles in the beginning). pH: 5 (25°C).

[0259] Example 3

[0260] Table 3

[0261] A powder mixture of Greenluronic, Sodium hydrogen carbonate, anhydrous Citric acid was mixed, and this powder mixture was poured into water.

[0262] Result: fast dissolving process, a liquid formulation is obtained immediately (small particles in the beginning). pH:

[0263] 6.4 (25°C).

[0264] Example 4

[0265] A powder mixture of Greenluronic, Sodium hydrogen carbonate, anhydrous Citric acid was mixed, and this powder mixture was poured into water.

[0266] Result: fast dissolving process, a liquid formulation is obtained immediately (small particles in the beginning). pH: 6.9 (25°C).

[0267] Example 5

[0268] Table 5

[0269] A powder mixture of EXCEPTIONHYAL HW (1 ,800-2,200), Sodium hydrogen carbonate, anhydrous Citric acid was mixed, and this powder mixture was poured into water.

[0270] Result: fast dissolving process, a liquid formulation is obtained immediately (small particles in the beginning). pH: 6.5 (25°C).

[0271] Example 6

[0272] Table 6

[0273] A powder mixture of Greenluronic and Sucrose was mixed, and this powder mixture was poured into water.

[0274] Result: fast dissolving process, a liquid formulation is obtained immediately (small particles in the beginning). pH:

[0275] 7.7 (25°C).

[0276] Example 7

[0277] Table 7

[0278] A powder mixture of Greenluronic and Tripotassium citrate monohydrate was mixed, and this powder mixture was poured into water. Result: fast dissolving process, a liquid formulation is obtained immediately (small particles in the beginning). pH: 8.0 (25°C).

[0279] Example 8

[0280] Table 8 A powder mixture of Greenluronic and Potassium gluconate was mixed, and this powder mixture was poured into water.

[0281] Result: fast dissolving process, a liquid formulation is obtained immediately. pH: 8.1 (25°C). Example 9

[0282] Table 9

[0283] A powder mixture of Greenluronic and Sodium gluconate was mixed, and this powder mixture was poured into water.

[0284] Result: fast dissolving process, a liquid formulation is obtained immediately (small particles in the beginning). pH: 8.0 (25°C).

[0285] Example 10 Table 10

[0286] A powder mixture of EXCEPTIONHYAL HW (1,800-2,200) and Sodium gluconate was mixed, and this powder mixture was poured into water.

[0287] Result: fast dissolving process, a liquid formulation is obtained immediately (small particles in the beginning). pH: 7.8 (25°C).

[0288] Example 11

[0289] A powder mixture of Greenluronic and Potassium gluconate and Citric acid was mixed, and this powder mixture was poured into water.

[0290] Result: fast dissolving process, a liquid formulation is obtained immediately. pH: 4.9 (25°C).

[0291] A powder mixture of Greenluronic and Sodium gluconate and Citric acid was mixed, and this powder mixture was poured into water. Result: fast dissolving process, a liquid formulation is obtained immediately (small particles in the beginning). pH: 5.30 (25°C).

[0292] Example 13

[0293] A powder mixture of Greenluronic, Sodium gluconate, Erythritol and Citric acid was mixed, and this powder mixture was poured into water.

[0294] Result: fast dissolving process, a liquid formulation is obtained immediately (small particles in the beginning). pH: 5.5 (25°C).

[0295] Example 14

[0296] Table 14

[0297] A powder mixture of was prepared and this powder mixture was poured into water.

[0298] Result: fast dissolving process, a liquid formulation is obtained immediately (small particles in the beginning). Example 15

[0299] Table 15

[0300] A powder mixture of Greenluronic, Sodium gluconate and Tripotassium Citrate monohydrate was mixed, and this powder mixture was poured into water.

[0301] Result: fast dissolving process, a liquid formulation is obtained immediately (small particles in the beginning).

[0302] Example 16

[0303] Table 16

[0304] A powder mixture of Greenluronic and Erythritol was mixed, and this powder mixture was poured into water.

[0305] Result: fast dissolving process, a liquid formulation is obtained immediately. pH: 7.3 (25°C). Example 17

[0306] Table 17

[0307] A powder mixture of Greenluronic, Sodium gluconate, Tripotassium Citrate monohydrate and the color Vanilla Yellow P-WS was mixed and this powder mixture was poured into water. Result: fast dissolving process, a liquid formulation is obtained immediately (containing small particles in the beginning). pH: 7.3 (25°C).

Claims

AMENDED CLAIMS received by the International Bureau on 09 September 2025 (09.09.2025)1 . A fast dissolving powder composition comprising or, alternatively, consisting of high molecular weight hyaluronic acid (HMW-HA) having an average molecular weight equal to or bigger than 1 ,000 kDa in combination with at least one dissolving aid component which is selected from the group comprising or, alternatively, consisting of:(I) an effervescent system that comprises at least one basic substance which is selected from carbonate or bicarbonate, and at least one acid substance which is selected from citric or tartaric acid, and mixtures thereof;(ii) at least one water-soluble salt which is selected from a water-soluble alkali-metal citrate salt, a water- soluble alkali-metal gluconate salt, a water-soluble alkali-earth metal citrate salt, a water-soluble alkali-earth metal gluconate salt, and mixtures thereof, wherein said fast dissolving powder composition is a mixture of powders and / or granules.

2. The fast dissolving HMW-HA composition according to claim 1, wherein said at least one dissolving aid component is selected from (ill) at least one sugar which is selected from the group comprising or, alternatively, consisting of sucrose, lactose, maltose, trehalose, erythritol, xylitol, maltitol, sorbitol, mannitol, or mixtures thereof.

3. The fast dissolving HMW-HA composition according to claim 1 or 2, wherein said high molecular weight hyaluronic acid (HMW-HA) has an average molecular weight comprised from 1 ,000 kDa to 10,000 kDa; preferably, it has a molecular weight comprised from 1 ,000 kDa to 8,000 kDa, more preferably, it has a molecular weight comprised from 1 ,000 to 7,000 kDa, even more preferably, it has a molecular weight comprised from 1 ,000 kDa to 6,000 kDa.

4. The fast dissolving HMW-HA composition according to anyone of claims 1-3, wherein said high molecular weight hyaluronic acid (HMW-HA) has an average molecular weight comprised from 1 ,500 kDa to 4,000 kDa.

5. The fast dissolving HMW-HA composition according to anyone of claims 1-4, wherein said basic substance of said (I) an effervescent system is preferably selected from the group comprising or, alternatively, consisting of carbonate or bicarbonate salts more preferably, sodium and / or potassium carbonate, sodium and / or potassium bicarbonate, or mixtures thereof; and said at least one acidic substance of said (I) an effervescent system is preferably selected from the group comprising or, alternatively, consisting of organic acids, more preferably a hydroxy acids, even more preferably citric acid and / or tartaric acid.

6. The fast dissolving HMW-HA composition according to anyone of claims 1-5, wherein said (II) at least one water- soluble salt is preferably selected from the group comprising or, alternatively, consisting of a water-soluble alkali- metal citrate salt, a water-soluble alkali-metal gluconate salt, a water soluble alkali-earth metal citrate salt, a water soluble alkali-earth metal gluconate salt, and mixture thereof; more preferably, tripotassium citrate, tripotassium citrate monohydrate, potassium gluconate, sodium gluconate, and mixtures thereof.

7. The fast dissolving HMW-HA composition according to anyone of claims 1-6, wherein said (ill) at least one sugaris preferably selected from the group comprising or, alternatively, consisting of sucrose, maltitol, erythritol, xylitol or mixtures thereof.

8. The fast dissolving HMW-HA composition according to anyone of claims 1-7, wherein said composition further comprises:- at least one flavour and / or colorant and / or sweetener and / or surfactants and / or a carrier and / or at least one excipient of pharmaceutical or food grade; and / or- at least a pH adjusting agent, preferably an organic acid; more preferably at least one hydroxy acid, even more preferably citric acid and / or tartaric acid and / or mixture thereof; and / or- at least one further active ingredient.

9. The fast dissolving HMW-HA combination or composition according to anyone of claims 1-8, wherein said combination or composition comprises or, alternatively, consists of HMW-HA and (I) an effervescent system, and (ii) at least one water-soluble salt and / or (ill) at least one sugar, and an acacia gum.

10. A process for preparing an HMW-HA water-based fluid composition, wherein said process comprises: a) putting into contact a fast dissolving composition according to anyone of claims 1-9 with a water-based fluid which is selected from the group comprising or, alternatively, consisting of water, milk, plant-based milk, fruit drink, energy drink, fortified drink, herbal drink, sport drink, yogurt drink, buttermilk drink, probiotic drink, a nectar, a juice or cappuccino, smoothie, coffee, cafe au lait, coffee milk, cacao, or mixtures thereof, to obtain a product; b) mixing said product for a time comprised from 5 seconds to 5 minutes, preferably from 30 seconds to 3 minutes, at a temperature comprised from 18 °C to 40°C, preferably comprised from 18°C to 25 °C, to obtain said HMW- HA water-based fluid composition.

11. The process for preparing an HMW-HA water-based fluid composition according to claim 10, wherein said composition is for oral use, preferably is drinkable composition for oral use, or is for topical use, preferably is a spray product for topical use.

12. An HMW-HA water-based fluid composition which is obtained by the process according to claim 10.

13. A drinkable HMW-HA water-based fluid composition for oral use which is obtained by the process according to claims 10 and 11.

14. A water-based HMW-HA product for topical use, preferably a spray product for topical use which is obtained by the process according to claims 10 and 11 .

15. The water-based HMW-HA spray product for topical use according to claim 14, wherein said product is selected from the group comprising or, alternatively, consisting of mouth spray, topical spray for the skin or joints, lung spray.

16. A fast dissolving HMW-HA powder composition according to any one of claims 1-9, or a drinkable HMW-HA water-based fluid composition according to claim 13, or a water-based HMW-HA spray product according to claims 14 or 15, for use in a method for the treatment of joint diseases, and osteoarthritic or osteoarthritis diseases, for supporting joint health, or for supporting skin health or derma health, or for counteracting skin aging, or for a glowing skin, or for moisturised and supple skin, or for the treatment of oral cavity diseases, lung diseases, for supporting oral cavity health, or supporting lung health in a subject in need.

17. A non-therapeutic use of a fast dissolving HMW-HA powder composition according to any one of claims 1-9, ora drinkable HMW-HA water-based fluid composition according to claim 13, or a water-based HMW-HA spray product according to claims 14 or 15, for use for supporting joint health, or for supporting skin health or derma health, or for counteracting skin aging, or for a glowing skin, or for moisturised and supple skin, or for supporting oral cavity health, or supporting lung health.

18. Use of at least one dissolving aid component which is selected from group comprising or, alternatively, consisting of:(i) an effervescent system that comprises at least one basic substance which is selected from carbonate or bicarbonate, and at least one acid substance which is selected from citric or tartaric acid, and mixtures thereof;(ii) at least one water-soluble salt which is selected from a water-soluble alkali-metal citrate salt, a water- soluble alkali-metal gluconate salt, a water-soluble alkali-earth metal citrate salt, a water-soluble alkali-earth metal gluconate salt, and mixtures thereof; for preparing a fast dissolving powder composition comprising a high molecular weight hyaluronic acid (HMW-HA) having an average molecular weight equal to or bigger than 1 ,000 kDa, wherein said fast dissolving powder composition is a mixture of powders and / or granules that when is poured into a water-based fluid at a temperature comprised from 18 °C to 40°C, preferably comprised from 18°C to 25 °C, and stirred, preferably with the aid of a spoon, it gives, within a time from 10 seconds to 5 minutes, preferably from 1 minute to 3 minutes, a solution or a homogeneous fine dispersion free of lumps, insoluble bottom residue, precipitates.

19. Use according to claim 18, wherein said at least one dissolving aid component is selected from (iii) at least one sugar which is selected from sucrose, lactose, maltose, trehalose, erythritol, xylitol, maltitol, sorbitol, mannitol, or mixtures thereof.

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