HK40002677A

HK40002677A - Oral medication formulations

Info

Publication number: HK40002677A
Application number: HK19126180.9A
Authority: HK
Inventors: J‧休斯; C‧博普; B‧沃德罗普-布朗
Original assignee: 固荣私人有限公司
Priority date: 2016-10-20
Filing date: 2017-10-20
Publication date: 2020-03-27

Description

Oral pharmaceutical preparation

Background of the invention:

as the population ages and the survival rate of many injuries and diseases increases, the number of people with chronic conditions that affect health is increasing. 9000 million Americans had one or more chronic conditions according to the national medical expense survey of 1987. Treatment of these chronic conditions accounts for over 76% of healthcare expenditures, and by 2030 the total direct cost of treating these chronic conditions is estimated to increase to $ 7980 billion.

Chronic conditions that affect health are conditions that last for a long period of time and may or may not be cured. In such cases, the patient needs to maintain the treatment regimen for months and years. Many patients with chronic conditions receive treatment at home. Unfortunately, many patients may not be able to reliably manage their therapy at home without supervision by a healthcare provider.

The reference to any prior art in this specification is not, and should not be taken as, an acknowledgment or any form of suggestion that prior art forms part of the common general knowledge.

Summary of the invention:

the present invention relates to effervescent formulations of drugs, medical foods or supplements or some combination of these, for example for reducing treatment interruption and increasing treatment compliance of patients and consumers suffering from chronic conditions affecting health.

The present invention provides formulations comprising one or more active ingredients, a suspending base and an effervescent agent, wherein the active ingredients comprise one or more B vitamins. The suspension base may comprise a base-forming component and a thickening (or viscosity) component, wherein the thickening/viscosity component is optionally provided by the presence of one or more hydrocolloids. The matrix-forming component may comprise one or more of the following: inulin, dextrin, maltodextrin and potato dextrin. Preferably, the matrix forming component may comprise inulin.

The thickening/viscosity component may include one or more of the following: xanthan gum, carboxymethylcellulose, hydratable methylcellulose, sodium carboxymethylcellulose, sodium methylcellulose, microcrystalline cellulose groups, other gums such as guar gum, pectin, or other hydrocolloids, agar, carrageenan. In some embodiments, the thickening (or viscosity) component comprises xanthan gum, preferably pre-hydrated xanthan gum.

In some embodiments, the effervescence produced aids in mixing the ingredients of the formulation upon addition of water, thereby enhancing the formation of a suspension.

The invention also provides a product for dilution to prepare liquid serves (serves) comprising, for example, optionally one or more of from about 5 to 40mg, optionally from 10 to 30mg and optionally from about 15-20mg of active ingredient per 200ml serving.

The phrase "physiologically acceptable salts, esters, or derivatives thereof" as used herein refers to the various salts, esters, or derivatives referred to as various salts, esters, or derivatives of a molecule that would be understood by a skilled artisan as being physiologically acceptable such that one or more of them (and, for example, a plurality of them in combination) can be used in place of the molecule specified.

The present invention also provides a composition comprising:

0.1-100mg, optionally 1 to 80mg, optionally 10 to 50mg, optionally 12 to 25mg, optionally 10 to 20mg of L-methyl folic acid or a physiologically acceptable salt, ester or derivative thereof;

0.1 to 10mg, optionally 0.3 to 8mg, optionally 0.5 to 5mg, optionally 0.5 to 2mg, optionally 0.6 to 1.2mg of cyanocobalamin or a physiologically acceptable salt, ester or derivative thereof;

10 to 1000mg, optionally 20 to 800mg, optionally 40 to 400mg, optionally 80 to 300mg, optionally 120 to 200mg of a flavor additive, optionally a natural flavor additive and optionally a pink grapefruit flavor, and the like;

80 to 8000mg, optionally 200 to 4000mg, optionally 400 to 2000mg, optionally 600 to 1000mg, optionally 750 to 900mg of inulin, which is optionally instant inulin-fibril;

3 to 300mg, optionally 10 to 200mg, optionally 15 to 100mg, optionally 25 to 50mg, optionally 25 to 35mg of sucralose;

80 to 8000mg, optionally 200 to 4000mg, optionally 400 to 2000mg, optionally 600 to 1000mg, optionally 750 to 900mg of glucose syrup, optionally glucose solids-rice;

sodium carbonate in the range 40 to 5000mg, optionally 80 to 3000mg, optionally 100 to 1000mg, optionally 200 to 800mg, optionally 400 to 600 mg;

150 to 15000mg, optionally 300 to 10,000mg, optionally 500 to 5000mg, optionally 1000 to 2000mg, optionally 1200 to 1700mg of anhydrous citric acid;

1 to 200mg, optionally 1 to 100mg, optionally 1 to 50mg, optionally 1 to 30mg, optionally 10 to 22mg of natural pigment;

1 to 200mg, optionally 1 to 100mg, optionally 1 to 50mg, optionally 1 to 30mg, optionally 10 to 22mg of 200 mesh xanthan gum;

from 40 to 5000mg, optionally from 80 to 3000mg, optionally from 100 to 1000mg, optionally from 200 to 800mg, optionally from 450 to 650mg of sodium bicarbonate.

The present invention also provides a composition comprising:

0.1 to 10mg, optionally 0.3 to 8mg, optionally 0.5 to 5mg, optionally 0.8 to 4mg, optionally 1.5 to 3mg of L-methyl folic acid or a physiologically acceptable salt, ester or derivative thereof;

0.1 to 10mg, optionally 0.3 to 8mg, optionally 0.5 to 5mg, optionally 0.9 to 3.5mg, optionally 1.5 to 3mg of cyanocobalamin or a physiologically acceptable salt, ester or derivative thereof;

0.1-200mg, optionally 1 to 120mg, optionally 10 to 100mg, optionally 20 to 80mg, optionally 40 to 60mg of vitamin B6 or a physiologically acceptable salt, ester or derivative thereof;

50 to 15000mg, optionally 150 to 10000mg, optionally 500 to 5000mg, optionally 1000 to 2000mg, optionally 1500 to 2500mg of omega-3 fatty acids, optionally comprising docosahexaenoic acid (DHA) or eicosapentaenoic acid (EPA) or mixtures thereof;

80 to 8000mg, optionally 200 to 4000mg, more optionally 400 to 2000mg, optionally 600 to 1000mg, optionally 750 to 900mg of inulin, optionally instant inulin-fibrils;

80 to 8000mg, optionally 200 to 4000mg, more optionally 400 to 2000mg, preferably 600 to 1000mg, optionally 750 to 900mg of glucose syrup, optionally glucose solids-rice;

150 to 15000mg, optionally 300 to 10000mg, optionally 500 to 5000mg, optionally 1000 to 2000mg, optionally 1200 to 1700mg of anhydrous citric acid;

In some preferred embodiments of the composition, 0.1 to 2mg, optionally 0.2 to 1.5mg, optionally 0.5 to 1.3mg, optionally 0.6 to 1.2mg, optionally 0.7 to 1.1mg, optionally 0.8 to 1.0mg, optionally 0.89mg of vitamin B6 or a physiologically acceptable salt, ester or derivative thereof is provided.

In some preferred embodiments of the composition, 35 to 55mg, optionally 40 to 48mg, optionally 42 to 46mg, optionally 43 to 45mg, optionally 44.1mg, optionally 20mg of vitamin B6 or a physiologically acceptable salt, ester or derivative thereof is provided.

In some preferred embodiments of the composition, from 0.001 to 0.02mg, optionally from 0.002 to 0.015mg, optionally from 0.005 to 0.013mg, optionally from 0.006 to 0.012mg, optionally from 0.007 to 0.011mg, optionally from 0.008 to 0.01mg, optionally 0.0089mg of cyanocobalamin or a physiologically acceptable salt, ester or derivative thereof is provided.

In some preferred embodiments of the composition, 0.5 to 7mg, optionally 1 to 5mg, optionally 2 to 3mg, optionally 2.1 to 2.4mg, optionally 2.21mg, optionally 0.5mg of cyanocobalamin or a physiologically acceptable salt, ester or derivative thereof is provided.

In some preferred embodiments of the composition, docosahexaenoic acid (DHA) is provided in an amount selected from 100 or 200 or 300 or 400 or 500 or 600 or 700 mg.

In some preferred embodiments of the composition, the L-methyl folic acid or a physiologically acceptable salt, ester or derivative thereof is provided in an amount selected from 1.1 or 2 or 3 or 4 or 5 or 6 or 7 or 8 mg.

The present invention also provides a composition comprising:

80 to 8000mg, optionally 200 to 4000mg, optionally 400 to 2000mg, optionally 600 to 1000mg, optionally 750 to 900mg of inulin, optionally instant inulin-fibrils;

The invention also provides a method of ameliorating or alleviating a clinical symptom of a brain-related disorder comprising administering a formulation or composition according to the invention.

The invention also provides an effervescent formulation comprising at least one active agent, at least one pharmaceutically acceptable effervescent acid, at least one further effervescent base and at least one further excipient, wherein the active agent comprises B vitamins and optionally folic acid or a folic acid derivative.

The invention provides a formulation comprising B vitamins, characterized in that the formulation comprises an effervescent couple consisting of at least one effervescent acid and at least one effervescent base and at least one pharmaceutically acceptable excipient.

The present invention provides a product comprising: one or more natural isomers of reduced folates selected from the group consisting of: (6S) -tetrahydrofolic acid, 5-methyl- (6S) -tetrahydrofolic acid, 5-formyl- (6S) -tetrahydrofolic acid, 10-formyl- (6R) -tetrahydrofolic acid, 5, 10-methylene- (6R) -tetrahydrofolic acid, 5, 10-methenyl- (6R) -tetrahydrofolic acid, 5-formimino- (6S) -tetrahydrofolic acid, and polyglutamyl derivatives thereof; and a foaming (fizz) composition comprising an acid and a base component, wherein the foaming composition reacts to foam in the food product when mixed with the aqueous liquid.

The present disclosure provides a novel combination of effervescence with a drug to be taken for chronic conditions affecting health. The formulations of the present invention enable the drug to be more easily and ideally taken and improve treatment compliance by reducing treatment interruptions.

In one aspect of the invention, a formulation is provided comprising an active ingredient, a suspending base and an effervescent agent. It has been found that the formulations according to the invention are particularly preferred for poorly soluble active ingredients. An example of such a component is the calcium salt of L-methyl folate. Preferably, the suspension base comprises a base-forming component and a thickening (or viscosity) component. In some preferred embodiments, the thickening/viscosity component is provided by the presence of one or more hydrocolloids.

In one aspect of the invention, an effervescent formulation is provided comprising at least one active agent, at least one pharmaceutically acceptable effervescent acid, at least another effervescent base, and at least another excipient. In some preferred embodiments, the active agent(s) comprise vitamin B, and in some embodiments, folic acid or a folic acid derivative.

In a further aspect of the present invention there is provided a formulation comprising vitamin B (e.g. folic acid or a folic acid derivative), characterised in that the formulation comprises an effervescent couple consisting of at least one effervescent acid and at least one effervescent base and at least one pharmaceutically acceptable excipient, and being in effervescent form.

In another aspect of the invention, there is provided a food product, food product for a specific medical purpose, medicament, supplement having a foaming component for chronic conditions affecting health. Another aspect of the invention includes a food product, supplement, food product for a specific medical purpose, pharmaceutical or medical food product having a foaming component.

In one embodiment, the present invention relates to a composition comprising one or more natural isomers of reduced folic acid. The one or more natural isomers of reduced folate are selected from the group consisting of (6S) -tetrahydrofolic acid, 5-methyl- (6S) -tetrahydrofolic acid, 5-formyl- (6S) -tetrahydrofolic acid, 10-formyl- (6R) -tetrahydrofolic acid, 5, 10-methylene- (6R) -tetrahydrofolic acid, 5, 10-methenyl- (6R) -tetrahydrofolic acid, 5-formimino- (6S) -tetrahydrofolic acid, and polyglutamyl derivatives thereof.

In some embodiments, the present invention provides a novel combination of effervescence with 1-methylfolic acid in all forms and isomers as a medical food, food for special medical purposes, a medicament, a supplement for various disorders including, but not limited to, alzheimer's dementia, depression, neural tube defects, diabetes and other disorders. The purpose of this combination is to make the medication easier and more desirable to take and to improve treatment compliance by reducing treatment interruptions.

In one aspect, the invention provides a product comprising:

a medical food for chronic conditions affecting health, a food for special medical purposes, a nutritional supplement, a pharmaceutical product, a nutraceutical, a dietary composition or any compound, powder, herb or treatment, and a foaming composition comprising an acid and a base component, wherein the foaming composition reacts to foam in the food when mixed with an aqueous liquid.

In some embodiments, the invention further comprises administering a substance for supporting, preventing, treating, or addressing a disease state, including supporting a nutritional deficiency associated with the disease state, reducing or controlling symptoms of the disease, curing the disease, or treating side effects of the disease.

As used herein, an effervescent compound is any compound that effervesces when mixed with a liquid-regardless of the chemical process. As used herein, a treatment regimen refers to the consumption of a compound at a recommended or prescribed dosage and at a desired frequency and time. As used herein, a recommended or desired medication may be provided by a prescribing healthcare practitioner, the manufacturer, or some other health practitioner. As used herein, a medical practitioner is a health professional, including a doctor, physical therapist, pharmacist, occupational therapist, dietician, geriatric doctor, psychologist, psychiatrist, specialist, therapist, or some other health professional. The supplement as used herein may be a powder, a tablet, a capsule or take some other form. The skilled person will appreciate that the product according to the invention may comprise other ingredients not listed herein.

In another aspect, the invention provides a product comprising: one or more natural isomers of reduced folate selected from the group consisting of (6S) -tetrahydrofolic acid, 5-methyl- (6S) -tetrahydrofolic acid, 5-formyl- (6S) -tetrahydrofolic acid, 10-formyl- (6R) -tetrahydrofolic acid, 5, 10-methylene- (6R) -tetrahydrofolic acid, 5, 10-methenyl- (6R) -tetrahydrofolic acid, 5-formimino- (6S) -tetrahydrofolic acid, and polyglutamyl derivatives thereof; and a foaming composition comprising an acid and a base component, wherein the foaming composition reacts to foam in the food product when mixed with the aqueous liquid.

Throughout this specification (including any claims which follow), unless the context requires otherwise, the word "comprise", and variations such as "comprises" and "comprising", will be understood to imply the inclusion of a stated integer or step or group of integers or steps but not the exclusion of any other integer or step or group of integers or steps.

Detailed description of exemplary embodiments:

the present invention is conveniently described herein in terms of a particularly preferred embodiment. However, the invention is applicable to many embodiments and products, and it is to be understood that other configurations and arrangements are also contemplated as falling within the scope of the invention. Various modifications, changes, variations and or additions to the constructions and arrangements described herein are also contemplated as falling within the metes and bounds of the invention.

In one embodiment, the chronic condition may be associated with a deficiency of one or more folic acids. Folic acid is ubiquitous in almost all forms of life. Humans and many other animals lack the ability to produce their own folic acid, which is therefore an essential vitamin, an essential nutrient. Anemia, particularly during pregnancy and in the elderly population, is an early sign of dietary demand for folic acid. The main function of folic acid is to remove one-carbon units from the metabolized molecule and then deliver them to the molecule to be synthesized. For example, folic acid is involved in the formation of nucleic acids. In addition, the activity of DNA is controlled in part by methylation, and the main methylating agent of the body (S-adenosylmethionine) is produced in metabolic cycles involving folate. Therefore, many studies are concerned with the relationship between folate status and susceptibility to cancer, particularly colorectal adenomas.

Treatment regimens, whether or not for chronic conditions, generally indicate folate status can include taking medications, taking supplements, taking medical foods or foods for special medical purposes, adhering to a prescribed diet, and even exercise and other activities.

To be effective, drugs, medical foods and supplements must typically follow various schedules and dietary guidelines. For example, some are taken with food and some are not. Some drugs are taken only once a day, others are taken many times a day.

In such cases, patients are burdened with the unpleasant task of not only remembering what drugs/supplements/foods they need to take on any particular day or time of day, but also swallowing many different pills or capsules each day.

Keeping track of when and how much a drug, supplement or medical food is taken can become difficult as the number of drugs/supplements and/or medical foods taken simultaneously increases. Furthermore, pills, capsules and powders are more difficult to swallow for the elderly, very small and factory/digestive system impaired. Even when patients want to adhere to a regimen, they may fail involuntarily.

In addition, a phenomenon known as "pill fatigue" often develops in long-term consumers/patients. Pill fatigue is a phenomenon in which consumers resist taking their medications due to boredom, difficulty or period of swallowing, other causes, or forgetfulness. The process of adhering to their medical regimen becomes unpleasant or boring. Pill fatigue or resistance to treatment regimens, combined with unexpected or unintended non-compliance, results in a phenomenon known as "treatment interruption" (TI).

Unplanned or unforeseeable TI results in reduced compliance with treatment regimens. This has many consequences for the consumer/patient. First, the consumer does not receive the full benefits of a treatment regimen. Many compounds need to be at the desired level in the body in order to be effective. An insufficient level of a drug, medical food or related substance may mean that the treatment is only partially effective-or not effective at all.

Second, and more dangerously, it is difficult for the practitioner to determine whether the regimen is appropriate for the patient. This can lead to misdiagnosis where the practitioner considers the regimen to be ineffective when in fact the actual problem is that the drug is not taken in the correct dose. This may result in a higher dose, or a switch to another drug. It may even lead to misdiagnosis of the underlying condition.

Pharmaceutical companies have long been aware of the problem of TI, and there are many technologies that help to solve this problem. Various devices are known for assisting a patient to follow a treatment regimen. For example, McIntosh, U.S. Pat. No.4,837,719, describes a medication clock for indicating when multiple doses of medication should be taken. The McIntosh device also provides a record of when each medication was taken for comparison to the medication plan. In addition, the McIntosh device may monitor and record the temperature, blood pressure and pulse rate of the user.

Existing approaches typically involve some form of monitoring of compliance with a medication regimen, or device that administers the medication. Both of these items help to address the problem of therapy interruption by supervising compliance. They are actually "adherence" methods of compliance.

A better approach is to increase compliance by improving the "liking" of the drug/compound. Compliance with a treatment regimen is increased voluntarily, either by making the compound more pleasant to consume, or by making it an "interesting" part of the treatment regimen.

In one embodiment, the product comprises a medicament, medical food, food for special medical purposes, and/or supplement with a foaming component for chronic conditions affecting health. The product may be formed from a variety of compounds and may be a prescription or over-the-counter drug. Other ingredients such as sweeteners, flavoring agents, coloring agents, vitamins, minerals, preservatives and other compositions known to the skilled artisan may be added as desired.

As described herein, a foaming component is a compound or combination of compounds that releases a gas upon contact with an aqueous liquid to foam the product.

In one embodiment, the product comprises a pharmaceutical, medical food, food for a specific medical purpose, and/or supplement product consisting of one or more of its isomeric forms of 1-methylfolic acid in combination with a foaming component.

Such products are useful for treating, controlling the symptoms of, or supporting the nutritional needs of patients suffering from a wide variety of conditions including, but not limited to, alzheimer's dementia, depression, major depression, ADHD, ADD, ASD including autism, ASD, neurological Disorders, diabetes, and the like. The product may be a prescription or an over-the-counter. Other ingredients such as sweeteners, flavoring agents, coloring agents, vitamins, minerals, preservatives and other compositions known to the skilled artisan may be added as desired.

The product containing the effervescence component may be any material capable of exhibiting a "foaming" or effervescent effect. The product comprising the foaming components, all components, reactants, initiators, by-products and reaction products should be edible or not harmful to the consumer.

According to one embodiment of the invention, the product comprises a foaming component. The effervescence component reacts to effervescence or exhibit an effervescence effect when subjected to a liquid aqueous initiator. The liquid may be any liquid that induces a foaming effect. The product is typically mixed with water, which may be a suitable initiator. Other aqueous liquids, such as milk, buttermilk, fruit juices, and yogurt are also useful. Combinations of different liquids are also useful.

The liquid may be hot or cold depending on the requirements of the product. In one embodiment, the product reacts when subjected to a hot liquid. In one embodiment, the temperature of the hot liquid is near or at its boiling point. Other temperatures are also useful. Any temperature that is capable of initiating a reaction that results in a foaming or effervescent effect is suitable.

The foaming component typically comprises an acid and a base component. Any food grade combination of acid and base components that provides effervescence to the product without substantially adversely affecting the organoleptic properties and characteristics of the product is suitable. Thus, any acid/base pair that provides the gas released by the base to "bubble" the product is suitably used. Typically, the acid is a food grade acid in a concentration sufficient to react with the release gas, typically carbon dioxide (CO)₂) To provide a "foaming" or effervescent effect.

Any food grade acid may be used. The acid is selected to ensure that an effervescent effect is achieved but the flavour of the product is not adversely affected. In one embodiment, the acid component preferably comprises an anhydrous acid selected from the group consisting of tartaric acid, malic acid, fumaric acid, adipic acid, succinic acid, acetic acid, lactic acid, propionic acid, sorbic acid, phosphoric acid, and blends thereof. More preferably, the acid component comprises citric acid.

The base component includes any food grade alkaline compound that releases a gas upon reaction with the acid component to produce a foaming or effervescent effect. The gas released is limited only by the need to produce the edible product. Thus, the odor of the gas should be pleasant or harmless. Carbon dioxide gas is the preferred gas.

In one embodiment, the base component is selected from the group consisting of sodium, potassium, calcium, ammonium carbonates or bicarbonates and blends thereof. Preferably, the base component comprises calcium carbonate, sodium bicarbonate, or a combination thereof.

The relative proportions of the base component and the acid component are determined to ensure that the foaming or effervescent effect is effectively achieved without leaving an excess of unreacted base or acid component in the product. Unreacted alkali or acid components may adversely affect the flavour of the product. Thus, stoichiometric amounts of acid and base are generally used, with substantially no excess of acid or base. This method is used to ensure that substantially all of the base and acid components have been consumed by the effervescence reaction. Any minor acid or base components that are not reacted will remain in the product, generally without adversely affecting the organoleptic properties and characteristics of the product.

In one embodiment, the foaming component comprises from about 0.01 to about 10 weight percent, typically from about 0.05 to about 5 weight percent, of the acid component, and from about 0.01 to about 10 weight percent, typically from about 0.05 to about 5 weight percent, of the base component, all based on the total weight of the product. Preferably, the foaming component comprises a stoichiometric amount of each component. Thus, typically, the molar ratio of acid component to base component is about 1: 1, about 2 for carbonate: 1. the skilled person will be able to determine the appropriate molar ratio under the guidance provided herein. Other compositional ranges may also be useful.

The two-part (base and acid) foaming component is typically prepared before being added to the product. The preparation of the foaming component comprises, for example, grinding the acid and base components into granules or powders. The grinding should result in a uniform distribution of the components. Preferably, the components are prepared to reduce the formation of precipitates. This can be achieved by milling the acid and base components together. Suitable foaming components can be produced by separately milling the acid and base components and then blending to produce a uniform distribution.

For example, the particle size of the components of the foaming composition is selected to achieve a desired reaction rate. Generally, the reaction rate is inversely proportional to the particle size. Typically, the particles have an average particle size of 95% by weight of the particles are 42 mesh or finer. For example, higher reaction rates are achieved with smaller particles. In one embodiment, the average particle size of the components is determined such that 95% by weight of the particles are 80 mesh or finer. It is also useful to provide the foaming component with components of other particle sizes. As the skilled person realizes, the rate and duration of the effervescent effect will be different.

The prepared foaming component can be added to the product in various forms. In one embodiment, the foaming component is prepared for addition in dry form. For example, the foaming component is added as a powder in the desired amount. The frothed component is then blended with the other components to produce a uniform distribution. To prevent premature reaction between the acid and base prior to addition of the aqueous liquid, the moisture content of the components should be sufficiently low. For example, the moisture content should be less than about 15% by weight, preferably less than about 10% by weight. Alternatively, the foaming component may be encapsulated. The encapsulated effervescent component is unable to react to form a gas and exhibits an effervescent effect. Either component may be encapsulated to achieve this result. However, typically, when the acid component and the base component are mixed, particularly prior to milling, both components are encapsulated. However, care should be taken to ensure that the envelope is not broken during mixing of the foaming component and the other components.

The encapsulant can be any food-grade water-resistant coating. Typically, such coatings comprise a fat-based composition that is fluid at elevated temperatures, but cures at ambient temperatures (about 20 ℃ to about 30 ℃: about 68 ° F to about 86 ° F). Because the coating is solid at ambient temperature, the acid component and the base component cannot react. However, the coating breaks at elevated temperatures, i.e., the temperature at which the product is prepared for consumption. The acid and base components may then be combined to produce an effervescent effect or lather.

Suitable coatings for the particles include, for example, the coatings described in U.S. patent No.6,159,511, which is incorporated herein by reference. Various types of edible fat-based coatings may be used. Such edible fats may include, for example, cocoa, butter, coconut oil, soy, cottonseed, sunflower, canola, partially hydrogenated vegetable oils, and combinations thereof. These and other fats may be used to form the basis of a coating for the acid and base component particles. Sugar may also be added to the coating for flavoring. Another suitable coating is Mor-Rex 1918, hydrolyzed cereal solid with a dextrose equivalent of 10, available from CPC Industrial.

Other coatings may also be used. Waxes are generally soluble in warm fluids suitable for product preparation. Furthermore, the coating may comprise water-absorbing polymer molecules dispersed in the coating. The water-absorbent polymer swells and destroys the coating upon absorption of water. The coating then fails and the components can be mixed with each other.

To apply the acid and base components, a suitable coating is prepared and heated to become fluid. The acid and base components are then mixed into the fluid coating. The coating is then cured by cooling and the product is manufactured using the coated two-component mixture. The encapsulated product of this embodiment may then be cured in a manner known in the art. Solid slabs can be broken, but crushing or comminuting (massaging) slabs is difficult to accomplish well, i.e., to produce reasonably sized encapsulated products. Thus, particles are typically formed by spray coolers to form smaller, more manageable and usable droplets. Using the guidance provided herein, the skilled person will be able to form encapsulated solid particles for the acid and base components contained in the product.

In another embodiment, the foaming component is further processed to form a granule. The pellets may be added to the product in the desired amount. The processed granules may be coated. In one embodiment, the coating comprises edible fat. As described above, the granule coating may comprise a material for coating a single particle. As mentioned above, these coatings may also include coating obstructions (interpuncters) to ensure that the acid and base components are sufficiently reactive (and produce a complete "blistering" reaction).

The content of the fat-based coating is selected to have a desired melting point. The coating melts when subjected to an aqueous liquid at a temperature above the melting point of the coating. As the difference between the melting point and the liquid temperature increases, the melting rate increases. The water-soluble coating is dissolved in the aqueous liquid. At higher liquid temperatures, the dissolution rate is generally greater. This melting or dissolution of the coating exposes the foaming component to the aqueous liquid, resulting in a foaming or effervescent effect.

In one embodiment, the coating melts at a predetermined temperature. The predetermined temperature is for example less than or equal to the temperature of the hot liquid used for preparing the product. In one embodiment, the predetermined melting point temperature is about the temperature of the hot liquid used to prepare the product. When the coating is provided with a water-swellable aid, these water-based inclusions in the coating react upon wetting and tend to break the coating. Hot water, i.e. at or above the melting temperature of the fat-based material, will tend to melt more of the coating. Typical temperatures range from 20 ℃ to 100 ℃, preferably from 30 ℃ to 90 ℃, more preferably from 40 ℃ to 80 ℃.

The time required to expose the foamable composition can be determined by the thickness of the coating. The thicker the coating, the longer the time required. The thickness of the coating is selected such that the foaming component is exposed to the liquid within about 2 seconds to about 10 minutes. Depending on the desired application or product, the exposure time may be shorter or longer. For example, the exposure time may be selected to provide a foamed product after it is prepared and ready for consumption. In the case of coatings, then, the coating is thicker for non-instant type products than for instant products, so that the pellets can withstand the cooking time before melting or dissolving. Alternatively, the coated granules may be added after the food is prepared and ready for consumption, enabling the use of relatively thin coatings. Thus, the skilled artisan, with the guidance provided, can determine an appropriate coating thickness.

When added to an aqueous liquid, the product contains sufficient foaming components to cause a foaming or effervescent effect. Preferably, the foaming component is present in a sufficient amount to produce foaming for up to about 10 minutes, more typically from about 5 seconds to 5 minutes. Foaming can also be sustained during consumption of the product to provide a desirable mouthfeel (sensory) experience. For example, the duration may be selected to be relatively short to provide initial appeal or entertainment, but to stop foaming at the point of consumption. Similarly, coatings of various thicknesses may be applied to portions of the foaming component to provide a foaming or effervescent effect over a longer period of time.

Preferably, the amount of the foaming component is less than an amount that would adversely affect the taste of the product. Taste may be adversely affected by salts or other reaction products formed during the reaction or by unreacted alkali or acid components. It may also be desirable to provide a foaming component that does not impart a significant degree of gas, particularly a level of carbonation, to the aqueous liquid. In one embodiment, the foaming component, in addition to the aqueous liquid, comprises from about 0.01% to about 10% by weight, more typically from about 0.05% to about 5% by weight of the total weight of the product. Other percentages of foaming components may also be useful.

In another embodiment, the lathering component may be provided to the product in a combination of different forms. In another embodiment, the foaming component may be a hot product such as, for example, a carbonation source for instant or non-instant hot beverages.

The effervescent or effervescent component of the present invention may optionally comprise a pharmaceutically acceptable effervescent couple comprising an acid and a base, wherein the acid of the effervescent couple is selected from citric acid, tartaric acid, pamoic acid (amalic), fumaric acid (fumeric), adipic acid and succinic acid. The base of the effervescent couple is selected from the group consisting of sodium bicarbonate, sodium carbonate, potassium bicarbonate, potassium carbonate, and magnesium carbonate.

The effervescent reaction generally consists of

Acid + carbonate to produce CO₂+ acid salt + H₂O

For example: citric acid +3NaHCO₃To produce 3CO₂+ sodium citrate +3H₂O

An example of a carbonate is sodium carbonate (soda) Na₂CO₃And sodium bicarbonate (baking soda), 3NaHCO₃。

The acid component may be selected from the group consisting of citric acid, palmitic acid, boric acid, succinic acid, tartaric acid, malic acid, palmitic acid, fumaric acid, adipic acid, acetic acid, lactic acid, propionic acid, sorbic acid, phosphoric acid, acid salts, sodium bisulfate, and the like, and blends thereof.

The carbonate source material may be selected from alkaline earth metal carbonates and bicarbonates of sodium, potassium, calcium, ammonium, magnesium, and the like, and blends thereof.

The active compound of the dosage form of the present invention may be selected from one or more natural isomers of reduced folic acid selected from the group consisting of (6S) -tetrahydrofolic acid, 5-methyl- (6S) -tetrahydrofolic acid, 5-formyl- (6S) -tetrahydrofolic acid, 10-formyl- (6R) -tetrahydrofolic acid, 5, 10-methylene- (6R) -tetrahydrofolic acid, 5, 10-methenyl- (6R) -tetrahydrofolic acid, 5-formimino- (6S) -tetrahydrofolic acid, and polyglutamyl derivatives thereof.

The other active compounds may also be selected from vitamin B6, vitamin B12, omega-3 fatty acids such as DHA and EPA, etc.

In a particularly preferred embodiment, the present invention relates to the use of an algal source of DHA and/or EPA or any other non-fish source of DHA and/or EPA as a way to improve flavour and compliance with treatment. This is necessary because L-MF is insoluble and needs to be suspended in a liquid. Fish sources of EPA and/or DHA are unpalatable and unlikely to be consumed, easily leading to treatment interruptions.

In some embodiments, including the use of encapsulation and/or microencapsulation of some or all of the ingredients to improve flavor, e.g., encapsulation of fish or algae-based derivatives, the beverage will not have fishy taste and improve long-term stability by reducing the risk of fatty acid oxidation to form off-flavors.

Microencapsulation is a process of establishing a functional barrier between the core and wall materials to avoid chemical and physical reactions and to maintain the biological, functional and physicochemical properties of the core material, in this case a DHA-rich oil of marine origin. Microencapsulation of marine, plant and essential oils has been performed and commercialized by using different methods, including emulsification, spray drying, coaxial electrospray systems, freeze drying, coacervation, in situ polymerization, melt extrusion, supercritical fluid technology and fluidized-bed-coating. Spray drying and coacervation are the most commonly used techniques for microencapsulation of oils. The selection of appropriate microencapsulation techniques and wall materials depends on the end use of the product and the processing conditions involved. Microencapsulation enhances the oxidative stability, thermal stability, shelf life and bioactivity of the oil. Furthermore, it may also help to control sensory problems due to oxidation when using DHA, thus preventing sensory defects and off-flavours in the finished product.

In some aspects of the invention, other ingredients are added to suspend or enhance the solubility of the active ingredient (e.g., L-methyl folate). Some preferred embodiments include suspensions of active ingredients such as calcium L-methylfolate, which are produced using effervescence.

In some embodiments, the formulations according to the invention are used to help prevent or alleviate dementia and other similar disorders. It is therefore important to prepare formulations that are as easy to prepare as possible and to provide for the user to ingest. Thus, in some embodiments, effervescent forms are provided that comprise a suspension of an active ingredient, such as 5-methylfolic acid (e.g., metafolin). In some embodiments, the formulation may comprise a dispersion of the active ingredient, however, some of these embodiments are not organoleptically appealing and may not be preferred by the user.

In some embodiments, a formulation is provided comprising an active ingredient, a suspending base, and an effervescent agent. Preferably, the suspension base comprises a base-forming component and a thickening (or viscosity) component. In some preferred embodiments, the thickening/viscosity component is provided by the presence of one or more hydrocolloids.

The most important of these properties are solubility, viscosity (including thickening and gelling), and water of hydration, but many other properties are also important, including emulsion stability, resistance to ice recrystallisation and organoleptic properties.

In some embodiments, a formulation is provided comprising an active ingredient, a suspending base, and an effervescent agent. Preferably, the suspension base comprises a base-forming component and a thickening (or viscosity) component. In some preferred embodiments, the matrix forming component comprises inulin, and in some preferred embodiments, the thickening (or viscosity) component comprises xanthan gum.

It has been surprisingly found that in some particularly preferred embodiments, upon addition of water, the effervescent agent and resulting effervescence facilitates mixing of the ingredients of the formulation, thereby enhancing the formation of the suspension. This is important because a more complete suspension will have a greater percentage of the active substance trapped in it and therefore available for uptake. This is important because the active does not remain suspended for a long period of time, and it is important to consume the formulation while the active is suspended so that as much of the active ingredient as possible is actually consumed. By using effervescence, the formulation not only forms a suspension more quickly and completely, but also keeps it longer and is more organoleptically appealing to the user. In some preferred embodiments, each 200ml serving (serve) contains about 5 to 40mg, preferably 10 to 30mg, more preferably about 15 to 20mg of active ingredient, so it is important that all the active is consumed by the user.

It has been found that in some preferred embodiments, it is useful to use pre-hydrated xanthan gum because standard xanthan gum requires time to hydrate before it can contribute to the formation of a suspension. The pre-hydrated xanthan gum acts much faster, accelerating the formation of the suspension.

In some embodiments, the thickening/viscosity component may comprise one or more of the following: xanthan gum, carboxymethylcellulose, hydratable methylcellulose, sodium carboxymethylcellulose, sodium methylcellulose, microcrystalline cellulose groups, other gums such as guar gum, pectin (if any RTD), or other hydrocolloids such as agar, carrageenan. It is noted that further modifications may be required depending on the material chosen, for example in the case of carrageenan, which must be thermally processed rather than powdered.

In some embodiments, the matrix-forming component may comprise any one or more of the following: inulin (preferred because it has little flavor, is highly soluble, has good viscosity, etc.), dextrin, maltodextrin, potato dextrin (significant taste change). Note that maltodextrin is highly soluble, having a relatively low molecular weight, and therefore requires large amounts of maltodextrin to achieve the same viscosity as inulin (e.g., 10mg packaging may be required instead of 4gm of inulin). It is also noted that maltodextrin requires a longer time to hydrate and pectin can also be used-depending on its mode of use-because it forms a matrix as well as a gel-but it is not so good for powder formulations.

Other potential ingredients may include modified starches-corn, potato, tapioca (tapeocha) that will provide such viscosity and suspension.

According to a preferred embodiment, there is provided a composition comprising:

0.1-100mg, preferably 1 to 80mg, preferably 10 to 50mg, preferably 12 to 25mg, preferably 10 to 20mg of L-methylfolic acid or a physiologically acceptable salt, ester or derivative thereof;

0.1 to 10mg, preferably 0.3 to 8mg, preferably 0.5 to 5mg, preferably 0.5 to 2mg, preferably 0.6 to 1.2mg of cyanocobalamin or a physiologically acceptable salt, ester or derivative thereof;

10 to 1000mg, preferably 20 to 800mg, preferably 40 to 400mg, preferably 80 to 300mg, preferably 120 to 200mg of a flavor additive, which is preferably a natural flavor additive and preferably a pink grapefruit flavor or the like;

80 to 8000mg, preferably 200 to 4000mg, more preferably 400 to 2000mg, preferably 600 to 1000mg, preferably 750 to 900mg of inulin, which is preferably instant inulin-fibril;

3 to 300mg, preferably 10 to 200mg, preferably 15 to 100mg, preferably 25 to 50mg, preferably 25 to 35mg of sucralose;

80 to 8000mg, preferably 200 to 4000mg, more preferably 400 to 2000mg, preferably 600 to 1000mg, preferably 750 to 900mg of glucose syrup, which is preferably glucose solids-rice;

sodium carbonate in the range of 40 to 5000mg, preferably 80 to 3000mg, preferably 100 to 1000mg, preferably 200 to 800mg, preferably 400 to 600 mg;

150 to 15000mg, preferably 300 to 10000mg, preferably 500 to 5000mg, preferably 1000 to 2000mg, preferably 1200 to 1700mg of anhydrous citric acid;

1 to 200mg, preferably 1 to 100mg, preferably 1 to 50mg, preferably 1 to 30mg, preferably 10 to 22mg of natural pigment;

1 to 200mg, preferably 1 to 100mg, preferably 1 to 50mg, preferably 1 to 30mg, preferably 10 to 22mg of 200 mesh xanthan gum;

from 40 to 5000mg, preferably from 80 to 3000mg, preferably from 100 to 1000mg, preferably from 200 to 800mg, preferably from 450 to 650mg of sodium bicarbonate.

In some embodiments of the invention, methods of ameliorating or alleviating a clinical symptom of a brain-related disorder are provided comprising administering such compositions once a day. In some preferred embodiments, the brain-related disorder is depression or a disorder associated with depression.

0.1 to 10mg, preferably 0.3 to 8mg, preferably 0.5 to 5mg, preferably 0.8 to 4mg, preferably 1.5 to 3mg of L-methyl folic acid or a physiologically acceptable salt, ester or derivative thereof;

0.1 to 10mg, preferably 0.3 to 8mg, preferably 0.5 to 5mg, preferably 0.9 to 3.5mg, preferably 1.5 to 3mg of cyanocobalamin or a physiologically acceptable salt, ester or derivative thereof;

0.1-200mg, preferably 1 to 120mg, preferably 10 to 100mg, preferably 20 to 80mg, preferably 40 to 60mg of vitamin B6 or a physiologically acceptable salt, ester or derivative thereof;

50 to 15000mg, optionally 150 to 10,000mg, optionally 500 to 5000mg, optionally 1000 to 2000mg, optionally 1500 to 2500mg of omega-3 fatty acids, optionally comprising docosahexaenoic acid (DHA) or eicosapentaenoic acid (EPA) or mixtures thereof;

In some embodiments of the invention, methods of ameliorating or alleviating a clinical symptom of a brain-related disorder are provided, comprising administering such compositions once a day.

In some preferred embodiments, the brain-related disorder is dementia or a dementia-related disorder. During a two-year treatment of patients with Mild Cognitive Impairment (MCI), Smith et al found strong evidence that B vitamin treatment significantly altered Disease progression (The Journal of Albheimer's Disease (2017) Vol 3, pages 1-3.

In some preferred embodiments, the brain-related disorder is depression or a disorder associated with depression. In two multicenter sequential parallel comparison design experiments, Papakosatas et al concluded that 15 mg/day of supplemental L-methylfolate could constitute an effective, safe and relatively well-tolerated treatment strategy for patients with major depression who either partially or non-responded to SSRI (Am J Psychiatry 2012; 169: 1267-.

One skilled in the art will appreciate that formulations comprising salts or esters of the compounds of the present invention may also be used. For example, in some preferred embodiments, the calcium salt of L-methyl folate is preferred.

Example 1

Metafolin (calcium L-methylfolate) beverage is used for the dietary treatment of dementia and depression.

The following steps are described:

the powdered formulation is designed to produce a pleasant flavored effervescent fortified beverage containing Metafolin and other fortifying vitamins.

Mixing a powdered formulated beverage with drinkable tap water, stirring and drinking to treat depression or dementia in the form of a substantially light clear solution with a light natural color, which may be effervescent or quiescent, wherein 200ml portions comprise:

from about 1mg to about 50mg of the main bioactive compound in the L-calcium methylfolate-powdered beverage.

An amount of vitamin B12 (cyanocobalamin) and/or vitamin B6 (pyridoxine hydrochloride), wherein as an auxiliary biologically active compound each amount is between 10% and about 500% of the recommended daily value.

The amount of dry glucose powder as dispersed carbohydrate source is between 5% and 25% on a dry matter basis, which provides dispersion of the active ingredient and sweetness and body of the beverage.

The amount of natural flavouring ingredients is between 0.1% and 5.0% on a dry matter basis, with the aim of imparting a specific taste to the final beverage.

The amount of inulin (fructo-oligosaccharide) is between 1% and 50% on a dry matter basis, with the aim of improving the dispersion of the active ingredient and of providing a slightly thickened mouthfeel with the aim of improving the sensory perception.

The amount of polysaccharide gum comprising xanthan gum or guar gum or a combination of both, on a dry matter basis, is between 0% and 10% of the product, with the aim of suspending and evenly distributing the active ingredient in the final beverage and preventing the active ingredient from settling.

The amount of intense sweetener, either sucralose or asulfume-K or Neotame (Neotame) or a combination of these, on a dry matter basis, is from about 0.01% to 1% in order to sweeten the beverage.

On a dry matter basis, acting as an effervescent agent, alone or in combination, the amount of sodium carbonate, sodium bicarbonate and citric acid providing a pleasant lightly carbonated beverage when in contact with potable water in the beverage is from 10% to 50%.

Example 2

Two exemplary formulations according to one aspect of the invention include:

product 1

Product 2

In some embodiments, the formulation may additionally comprise a small amount of MHEC to reduce precipitation. For example, this may be less than or equal to 2%, preferably less than 1%, and in some preferred embodiments, about 0.1%.

In some embodiments, the formulation does not contain sucralose, and in some embodiments, lactose is replaced with another compound, such as mannitol or sorbitol. In some embodiments, the formulation further comprises sodium chloride to balance sweetness and saltiness. In some embodiments, alternative flavors are provided, such as strawberry, raspberry, cherry, and the like.

Example 3

Additional exemplary formulations (for a 4.5gm pouch of 30kg batch size) are as follows:

the product is a free-flowing fortified powdered beverage. It is made in water and provides a slightly effervescent pink grapefruit flavor and colored beverage with slight acidity and fruit sweetness.

For serving-the entire sachet was added to 200ml fresh water (which may be cold), stirred vigorously for 30 seconds, and drunk immediately.

For storage-below 25 ℃, the shady and cool place where direct sunlight is avoided.

Nutritional information:

manufacturing:

preparation before production

1. Pre-weighed vitamins were blended with 5 kg rice glucose syrup solids to make 100% vitamin premix for addition to the final formulation to improve mixing

Production of

2. All other raw materials were batched and blended in 30kg batches, sampled and the blended raw materials tested in the laboratory for consistency and uniform distribution, the product had to be sieved through a final screen <3 mm.

3. Samples should be taken and compared to the retained approved samples for flavor and color to ensure uniform blending, and if the samples do not match, blending will continue until the samples are acceptable.

4. The 20g of final blended product should be retained as a reference sample for production-this should be sealed in a suitable high barrier package and stored away from light, heat and volatile materials and labeled with product name, lot number and best use date (using a final carton label acceptable for traceability).

5. Once quality certified, the blended material was fed to the filling chamber and placed into a filling hopper.

6. It is now possible to fill the product into sachets-using the correct kind of preprinted film for each product, to 4.5g ± 0.25g, seal, encode the date and batch, and check for metal before final packaging.

7. Every 15 minutes the seal will be checked and if any defects are found, all the products produced from the previous 15 minutes will be isolated and inspected separately and any product found to be defective sealed will be rejected (rejected pouches with controlled unraveling can be reprocessed)

8. The products are packaged into cartons.

Example 4

Another exemplary formulation (for a 4.5gm pouch of 30kg batch size) is as follows:

the formulation is preferably for use in connection with improving depression in a subject suffering from depression.

One method of treatment is to add the entire sachet to 200ml of fresh water, stir vigorously for 3 seconds and drink immediately.

The product is a free-flowing fortified powdered beverage. It is made in water and provides a slightly effervescent pink grapefruit flavor and a yellow to pale pink beverage with slight acidity and fruity sweetness.

Nutritional information

The parts of each package are as follows: 1

The weight portions are as follows: 4.5g

	Average amount per portion	Average amount per 100g
			Energy of	36kJ(9Cal)	794kJ (190 card)
Protein	Less than 0.1g	Less than 0.1g
			Gluten	Not detected	Not detected
Fat, total	Less than 0.1g	Less than 0.1g
			-saturated	Less than 0.1g	Less than 0.1g
Carbohydrate compound	1.0g	22.1g
			-sugars	0.2g	4.4g
-lactose	0.0g	0.0g
			-galactose	0.0g	0.0g
Sodium salt	396mg	8790mg
			L-methyl calcium folate	15mg	333mg
Cyanocobalamin (B12)	1mg	22mg

This embodiment of the invention is free of artificial colors or flavors and is preservative free, gluten free, dairy products, peanuts and lactose free.

Example 5

Another exemplary formulation (for a 6.55gm pouch of 30kg batch size) is as follows:

the omega-3 fatty acids may be selected from any suitable acid, but are preferably selected from docosahexaenoic acid (DHA) or eicosapentaenoic acid (EPA), or mixtures thereof.

The formulation is preferably for use in connection with ameliorating dementia in a subject suffering from dementia. One method of treatment is to add the entire sachet to 200ml of fresh water, stir vigorously for 3 seconds and drink immediately.

Example 6

An exemplary method of preparation according to the present invention.

Preparation before production

1. Pre-weighed amounts of vitamins were mixed with rice glucose syrup solids to make 100% vitamin premix for addition to the final formulation to improve mixing.

2. The production chamber will be maintained at a relative humidity of 20-35% ERH max ERH 40% under regulation.

3. If the ERH of the packaging chamber is greater than 40%, the product is removed from the blending chamber or packaging chamber and sealed in an air tight container until the ERH drops below 35%.

Production of

4. All other raw materials were batched and blended in 30kg batches, sampled and the blended raw materials tested in the laboratory for consistency and uniform distribution.

5. Samples were taken and compared for flavor and color with the approved samples retained to ensure uniform blending. If the samples do not match, blending will continue until the samples are acceptable.

6. The product must be sieved through a final screen of <3 mm.

7. Once quality certified, the blended material was sent to a filling chamber and placed into a filling hopper.

8. The products can be filled into sachets-each product using the correct kind of preprinted film to 4.5+/-0.25g, sealed, date and batch coded, and X-ray detected before final packaging.

9. The seal was checked every 15 minutes and if any defects were found, all products produced from the first 15 minutes were isolated and individually inspected. Any product found to have a defective seal will be rejected.

10. The product is packaged into cartons, the pouches will be packaged in pre-printed lithographic solid fiber cartons at 30x 4.5 gram pouches each, closed with a tamper-resistant dart seal and date and batch encoded.

11. The package is then placed at the shipper x 6 and the carton date is coded as specified.

12. The cartons are placed into the pallet structure provided, the wrapping is tightened and a layer of padding is placed on top of each complete pallet to reduce the chance of dust ingress. Pallet labels will be attached to each pallet, with the product for each pallet being determined by the batch date and best-to-use date.

Example 7

Example 8

Example 9

Example 10

Example 11

the formulation is preferably for use in connection with ameliorating dementia in a subject suffering from dementia. One method of treatment is to add 200ml of fresh water to the entire sachet, stir vigorously for 3 seconds and drink immediately.

Example 12

Two other examples providing exemplary amounts of the various ingredients of the formulation according to the invention.

While the invention has been particularly shown and described with reference to various embodiments, it will be understood by those skilled in the art that modifications and changes may be made to the present invention without departing from the spirit and scope of the invention. The scope of the invention should, therefore, be determined not with reference to the above description, but instead should be determined with reference to the appended claims along with their full scope of equivalents.

The foregoing is illustrative of the present invention and is not to be construed as limiting thereof. Although a few exemplary embodiments of this invention have been described, those skilled in the art will readily appreciate that many modifications are possible in the exemplary embodiments without materially departing from the novel teachings and advantages of this invention. Accordingly, all such modifications are intended to be included within the scope of this invention as defined in the claims. Therefore, it is to be understood that the foregoing is illustrative of the present invention and is not to be construed as limited to the specific embodiments disclosed, and that modifications to the disclosed embodiments, as well as other embodiments, are intended to be included within the scope of the appended claims. The invention is defined by the following claims, with equivalents of the claims to be included therein.

Claims

1. A formulation comprising an active ingredient, a suspension base and an effervescent agent, wherein the active ingredient comprises one or more B vitamins.

2. The formulation of claim 1, wherein the suspension base comprises a base-forming component and a thickening (or viscosity) component, wherein the thickening/viscosity component is optionally provided by the presence of one or more hydrocolloids.

3. The formulation of claim 2, wherein the matrix-forming component comprises one or more of: inulin, dextrin, maltodextrin and potato dextrin.

4. The formulation of claim 2, wherein the matrix-forming component comprises inulin.

5. The formulation of claim 2, wherein the thickening/viscosity component comprises one or more of: xanthan gum, carboxymethylcellulose, hydratable methylcellulose, sodium carboxymethylcellulose, sodium methylcellulose, microcrystalline cellulose groups, other gums such as guar gum, pectin, or other hydrocolloids, agar, carrageenan.

6. The formulation of claim 2, wherein the thickening (or viscosity) component comprises xanthan gum.

7. The formulation of claim 6 comprising pre-hydrated xanthan gum.

8. The formulation of claim 1, wherein the effervescence produced facilitates mixing of the ingredients of the formulation upon addition of water, thereby enhancing the formation of the suspension.

9. The formulation of claim 1 for dilution to prepare 200ml servings comprising, per 200ml serving, optionally one or more of about 5 to 40mg, optionally 10 to 30mg and optionally about 15-20mg of active ingredient.

10. A composition, comprising:

11. A composition, comprising:

80 to 8000mg, optionally 200 to 4000mg, optionally 400 to 2000mg, optionally 600 to 1000mg, optionally 750 to 900mg of inulin, which is optionally instant inulin-fibrils;

12. A composition, comprising:

0.1 to 10mg, optionally 0.3 to 8mg, optionally 0.5 to 5mg, optionally 0.6 to 4mg, optionally 0.7 to 0.9mg, optionally 0.8mg, optionally 1.5 to 3mg of L-methyl folic acid or a physiologically acceptable salt, ester or derivative thereof;

0.001 to 10mg, optionally 0.1 to 8mg, optionally 0.5 to 5mg, optionally 0.9 to 3.5mg, optionally 1.5 to 3mg of cyanocobalamin or a physiologically acceptable salt, ester or derivative thereof;

0.1-200mg, optionally 1 to 180mg, optionally 10 to 100mg, optionally 20 to 80mg, optionally 40 to 60mg of vitamin B6 or a physiologically acceptable salt, ester or derivative thereof;

13. The composition of claim 12, comprising from 0.1 to 2mg, optionally from 0.2 to 1.5mg, optionally from 0.5 to 1.3mg, optionally from 0.6 to 1.2mg, optionally from 0.7 to 1.1mg, optionally from 0.8 to 1.0mg, optionally 0.89mg of vitamin B6 or a physiologically acceptable salt, ester or derivative thereof.

14. The composition of claim 12, comprising optionally 35 to 55mg, optionally 40 to 48mg, optionally 42 to 46mg, optionally 43 to 45mg, optionally 44.1mg, optionally 20mg of vitamin B6 or a physiologically acceptable salt, ester or derivative thereof.

15. A composition according to claim 12 comprising from 0.001 to 0.02mg, optionally from 0.002 to 0.015mg, optionally from 0.005 to 0.013mg, optionally from 0.006 to 0.012mg, optionally from 0.007 to 0.011mg, optionally from 0.008 to 0.01mg, optionally 0.0089mg of cyanocobalamin or a physiologically acceptable salt, ester or derivative thereof.

16. The composition according to claim 12, comprising optionally 0.5 to 7mg, optionally 1 to 5mg, optionally 2 to 3mg, optionally 2.1 to 2.4mg, optionally 2.21mg, optionally 0.5mg of cyanocobalamin or a physiologically acceptable salt, ester or derivative thereof.

17. The composition according to claim 12, comprising docosahexaenoic acid (DHA) in an amount selected from 100 or 200 or 300 or 400 or 500 or 600 or 700 mg.

18. The composition according to claim 12, comprising L-methyl folic acid or a physiologically acceptable salt, ester or derivative thereof in an amount selected from 1.1 or 2 or 3 or 4 or 5 or 6 or 7 or 8 mg.

19. A method of ameliorating or alleviating a clinical symptom of a brain-related disorder comprising administering the formulation or composition of any of the preceding claims once daily.

20. An effervescent formulation comprising at least one active agent, at least one pharmaceutically acceptable effervescent acid, at least one further effervescent base and at least one further excipient, wherein the active agent comprises B vitamins and optionally folic acid or folic acid derivatives.

21. A formulation comprising B vitamins, characterized in that it comprises an effervescent couple consisting of at least one effervescent acid and at least one effervescent base and at least one pharmaceutically acceptable excipient.

22. A product, comprising: one or more natural isomers of reduced folates selected from the group consisting of: (6S) -tetrahydrofolic acid, 5-methyl- (6S) -tetrahydrofolic acid, 5-formyl- (6S) -tetrahydrofolic acid, 10-formyl- (6R) -tetrahydrofolic acid, 5, 10-methylene- (6R) -tetrahydrofolic acid, 5, 10-methenyl- (6R) -tetrahydrofolic acid, 5-formimino- (6S) -tetrahydrofolic acid, and polyglutamyl derivatives thereof; and a foaming composition comprising an acid and a base component, wherein the foaming composition reacts to foam in the food product when mixed with the aqueous liquid.