Edible gel delivery method for health ingredients

Abstract

The present invention provides a method of edible gel delivery for health ingredients. The present invention relates to a dosage form of one or more healthy ingredients comprising glucose in a dose of not 50 g or 75 g, which is a drinkable gel. The health ingredient is retained in a delivery system comprising: water, a gelling agent, which is a carbohydrate nonionic gelling polymer gelling agent and / or a multivalent ionic gelling polymer gelling agent, and a pH adjusting agent. The ingredient is present in an amount that ensures the hydration and formation of a robust gel of Bloom rating from 100 to 250, which can be sheared to make it more flowable when ingested so that it is a drinkable gel. The invention further comprises a method comprising ingestion of the oral dosage form by squeezing and / or sucking the drinkable gel from a package comprising a pouch (1) having a pouch mouth (5) or having a straw.

Description

[0001] This application is a divisional application of a Chinese patent application with the application number "201980038931.1", the application date of May 8, 2019, and the invention title of "An Edible Gel Delivery Method for Health Ingredients".

[0002] The present invention relates to a dosage form comprising one or more health ingredients, particularly but not limited to nutritional ingredients.

[0003] The dosage form takes the form of a stable gel capable of delivering particularly multiple health ingredients in a single dosage form. The dosage form can be used for human or animal health.

[0004] The dosage form, particularly but not limited to, is capable of delivering high doses of nutritional and other health ingredients in a single delivery vehicle, including: water-soluble, water-insoluble, and / or fat-soluble ingredients, which are particularly not suitable for delivery by tablets or capsules.

[0005] Compared with current methods of delivering health ingredients, the dosage form has many benefits, and the gel is particularly suitable for delivering nutrients, food supplements, including meal replacements and drugs, in many different situations. Background of the Invention

[0007] One of the most important factors in the successful development of health, especially nutritional products, is to ensure patient compliance.

[0008] Currently, various product forms are used to deliver, for example, nutritional or other health ingredients. The nature and quantity of such products vary, resulting in significant variations in compliance.

[0009] These health products, including nutritional and health care products, can be prophylactic or therapeutic in nature. They include: prescription products, over-the-counter (OTC) products, health care products, and dietary supplements, including, for example, products containing: vitamins, minerals, elements, proteins, carbohydrates, lipids, extracts of plant origin, such as traditional Chinese medicine (TCM) or other indigenous medicines alone or in combination, etc.

[0010] Reasons for poor compliance may be the need to take, for example, multiple tablets, capsules, or other dosage forms, such as tablets containing multiple vitamins, capsules containing omega-3, beverages containing soluble fiber, etc.

[0011] Tablets and capsules can prove difficult to take (swallow), especially for certain patient groups, such as children and the elderly. For large-dose products or products that are difficult to formulate or combination products, large tablet sizes and multiple tablet doses can create compliance problems.

[0012] Other issues affecting patient compliance include the taste, odor, or sensory feel of the product. Sensory characteristics can relate to product taste, product consistency, product texture, product mouthfeel, taste duration, and any other aspect of sensory feel.

[0013] Some products require a separate beverage to facilitate swallowing or to wash residues from the mouth, or separate solid compositions that are co-administered.

[0014] Examples include: alternative sugar products for hypoglycemia, and whey protein, which has poor dispersion in liquids and additionally requires large amounts.

[0015] In addition, delivery devices such as spoons, syringes, or other metering devices may be required to assist with consumption and dose delivery. The requirement for such additional devices can have an adverse effect on compliance.

[0016] Other factors affecting efficacy include packaging, the chemical or physical stability of the composition, the bioavailability of the components, visual appeal, and ease of delivery.

[0017] Alternative dosage forms for capsules and tablets include beverages or gels that contain a liquid or semi-solid.

[0018] These "athletic gels" are typically high-viscosity pastes that contain thickeners such as xanthan gum. However, since these products do not set, they leave a residual tongue residue that can be unpleasant and can irritate the oropharyngeal area, leading to coughing or choking.

[0019] These high-viscosity paste or gel products are flowing but tend to flow slowly, have a high internal resistance, and have a consistency like honey or ketchup. These known high-viscosity pastes can be Newtonian or non-Newtonian fluids and can be shear-thinning or shear-thickening in nature. However, they all have the following characteristic: despite a certain degree of resistance, they will undergo plastic deformation under stress - even in cases where this behavior is known to have a threshold, such as exhibiting Bingham plastic behavior. Generally, these viscous pastes have a measurable viscosity between about 5000 and about 50,000 cP.

[0020] As used herein, the term "set" refers to a jelly material that sets and does not exhibit plastic behavior under stress but instead exhibits elasticity under stress until the failure point, at which point the structure of the jelly breaks, irreversibly creating new interfaces.

[0021] As disclosed in WO 2017 / 075672, the applicant has previously developed a novel glucose-containing product to facilitate the delivery of 50 g or 75 g doses of glucose for glucose tolerance (or similar) testing. The dose is dissolved in 100 ml of water and gelled using a mixture of agar (0.75 g) and locust bean gum (0.25 g).

[0022] Glucose is dissolved in water and gelled using one or more carbohydrate-based gelling agents: agar or a combination of agar and locust bean gum.

[0023] Compared with existing liquid dosage forms, the advantages of this novel dosage form are that the strong sweetness of glucose is masked, so that subjects taking glucose do not experience nausea, vomiting, dizziness and other emergency symptoms. It also delivers the dose in a smaller volume than traditional liquid tests.

[0024] The applicant has now determined that this general method of using a solidified gel to produce a delivery form with a defined Bloom grade can be more widely applied to facilitate the delivery of, for example, a wide range of health ingredients in addition to a fixed dose of glucose for diagnostic purposes.

[0025] They have further determined that further significant benefits can be obtained by using a specific combination of gelling agents.

[0026] Brief Description of the Invention

[0027] According to a first aspect of the present invention, there is provided an oral dosage form comprising one or more health ingredients, other than 50 g or 75 g doses of glucose, which is a drinkable gel, wherein the health ingredients are retained in a delivery system comprising:

[0028] · water,

[0029] · a gelling agent which is a polymer gelling agent for non-ionic gelling of carbohydrates and / or a polymer gelling agent for polyvalent ionic gelling, and

[0030] · a pH regulator

[0031] The ingredients are present in an amount that ensures hydration and formation of a firm gel with a Bloom grade of 100 to 250, which can be sheared to make it more fluid when ingested, so that it is a drinkable gel.

[0032] A firm gel is a "set" gel or jelly characterized by the Bloom test in an industrial and scientific context, which is used to provide the relative hardness and strength of these gels. This test was first conducted by Oscar T. Bloom in 1925. The test determines the weight (in grams) of a specified plunger (usually 0.5 inches (11 mm) in diameter) required to depress the surface of the gel by 4 mm at a specified temperature without irreversibly damaging the gel to form a new interface. This result is the Bloom grade. A higher number indicates a harder product. For example, gelatin used in food is typically between 125 Bloom and 250 Bloom.

[0033] For the purposes of this document, the terms gel and jelly are interchangeable.

[0034] The set gel or jelly is somewhat elastic, meaning that it will deform under stress, but when the stress is released, it will essentially return to its original form. For example, if the surface of a set jelly is gently pressed with the underside of a spoon, it will be pushed down, but when the spoon is removed, the original surface will return to its original position. It is not plastic, so under the same stress, the surface will deform and then remain deformed once the pressure is removed. If the stress is further increased beyond its failure point, the set gel or jelly will fail, undergoing irreversible damage and forming a new interface, rather than plastic deformation.

[0035] According to the use, the oral dosage form of the present invention can generally be provided in a volume of 25 ml to 250 ml and is delivered from a container, usually a sachet, through a nozzle or a straw, so that the sucking action shears the gel, making it more fluid when a new interface is formed, sometimes accompanied by the release of some water.

[0036] The advantages of shearing and the generation of a new interface are that it helps with delivery while maintaining taste masking.

[0037] According to a second aspect of the present invention, there is provided an oral dosage form comprising one or more health ingredients, the health ingredients being a drinkable gel, wherein the health ingredients are retained in a delivery system, the delivery system comprising:

[0038] · water,

[0039] · a primary gelling agent, which is a carbohydrate, a non-ionic gelling polymeric gelling agent,

[0040] · a secondary gelling agent, which is a polymeric gelling agent gelled by a polyvalent ion, and

[0041] · a pH regulator

[0042] The components are present in an amount to ensure hydration and formation of a firm gel having a bloom grade of 100 to 250, which firm gel can be sheared to make it more fluid upon ingestion so that it is a drinkable gel.

[0043] In the first and second aspects of the present invention, the oral dosage form is delivered through a narrow opening (such as a pouch mouth or a straw), and is sucked or squeezed, and the resulting delivery force and / or oral action shear the gel, thereby causing the formation of a new interface, making the preparation easy to ingest by drinking.

[0044] The carbohydrate gelling agent can be one of an agarose-based polymer gelling agent or locust bean gum. Most preferably, it is an agarose-based polymer gelling agent, such as agar.

[0045] The carbohydrate gelling agent used can also advantageously act as an emulsifier, so that a large amount of additional emulsifier is not required in a preparation containing non-polar components such as lipids (such as omega oils) and water-insoluble vitamins (such as vitamins D and E).

[0046] The polyvalent ion-gelled polymer is most preferably an alginate-based polymer gelling agent, such as but not limited to calcium alginate. Alternatives include guar gum, gellan gum, xanthan gum, pectin, and kudzu.

[0047] In a particularly advantageous embodiment, the gelling agent includes agar as the main gelling agent and calcium alginate as the secondary gelling agent. This combination has proven to be particularly versatile, allowing the combination of two or more water-soluble, water-insoluble, and / or lipid-based components to be formulated together in a single dosage form.

[0048] These two fundamentally different gelling agents provide a solidified gel structure through different interaction mechanisms. The advantage of this combination is its versatility as a basis, because this combination overcomes the situation where gelling is inhibited due to the presence of different components.

[0049] Agar consists of a mixture of two polysaccharides: agarose and agaropectin, and agarose accounts for about 70% of the mixture. Agarose is a linear polymer composed of repeating agarobiose units (a disaccharide composed of D-galactose and 3,6-anhydro-L-galactopyranose). Agaropectin is a heterogeneous mixture of smaller molecules, with a lower content, and is composed of alternating units of D-galactose and L-galactose that are heavily modified by acidic side groups (such as sulfuric acid and pyruvic acid). Any known variant of agar can be used in the present invention.

[0050] Agar exhibits hysteresis, melting at 85 °C and solidifying between 32 °C and 40 °C. At relatively high temperatures, this property strikes a suitable balance between easy melting and good gel stability. Agar is more suitable than other carbohydrate-based solidifying agents (such as gelatin) that also melt near this temperature.

[0051] Gelling also helps to provide stability at room temperature (and above), which means refrigeration can be avoided.

[0052] The most commonly used alginate in food is sodium alginate. To form a gel, sodium alginate needs to come into contact with divalent ions (such as calcium (Ca2+)). When sodium alginate is added to a solution of a calcium salt (such as chloride or citrate), sodium ions (Na+) are exchanged with calcium ions (Ca2+) to form a gel, and the polymer cross-links. Divalent ions (such as calcium) are able to form cross-links between alginate polymers because they can form two bonds, while monovalent ions (such as sodium) can only form one bond. The longer the contact time of alginate with a divalent ion solution, the harder the gel will become as more cross-links are formed. Similarly, depending on the concentration of the divalent ion, the gel can be thermoreversible (low concentration) or thermoirreversible (high concentration).

[0053] Alginic acid is a linear copolymer with homopolymer blocks of (1-4)-linked β-D-mannuronic acid (M) and its C-5 epimer α-L-guluronic acid (G), linked together in different sequences or blocks.

[0054] Sodium alginate is the sodium salt of alginic acid. Its empirical formula is NaC 6 H 7 O 6 . Sodium alginate is a gum that is extracted from the cell walls of brown algae.

[0055] Potassium alginate is a compound that is the potassium salt of alginic acid. Its empirical chemical formula is KC 6 H 7 O 6 .

[0056] The chemical formula of calcium alginate (where the sodium ions have been removed and replaced with calcium) prepared from sodium alginate is C 12 H 14 CaO 12 .

[0057] The gel formulation of the present invention can be used to deliver one or more of the following:

[0058] i) water-soluble components;

[0059] ii) water-insoluble components; and

[0060] iii) lipids; or

[0061] iv) Dietary substitutes or their main components, such as proteins, carbohydrates, fats, minerals, vitamins, and fibers, or combinations thereof.

[0062] In a first embodiment, the dosage form of the present invention has been shown to be very effective in promoting the delivery of rapidly released sugars, such as glucose, to address the "hypoglycemic events" in diabetic patients. Most preferably, the sugar is delivered together with one or more other health-beneficial ingredients and can be tailored for "at-risk" populations, such as children, adults, pregnant women, or the elderly.

[0063] Typically but not necessarily, a dose of 1 g to 40 g of the ingredient is delivered in a gel of 25 to 45 ml.

[0064] Delivering a single or main component or drug in this way (including much lower amounts of the active ingredient) may be beneficial in other emergency situations, such as epilepsy, allergic reactions, migraines, chest pain, asthma, etc.

[0065] The base gel formulation can be used to load a variety of health ingredients (including drugs) into an easy-to-take and easy-to-use dosage form, which can retain ingredients that are usually difficult to formulate into a single dosage form due to their different properties and can be administered orally by squeezing or sucking the gel from a container.

[0066] In a second embodiment, the dosage form contains health ingredients targeted at addressing specific health requirements of a target group of subjects based on, for example, lifestyle. Non-limiting examples include:

[0067] Students - In this case, the gel has been formulated to assist with learning and may contain nutrients to enhance brain cell function, improve alertness, memory, attention, concentration, and endurance. It can also help reduce stress;

[0068] Outdoor workers - In this case, the gel has been formulated to provide natural anti-inflammatory agents and antioxidants to assist with post-work muscle relaxation and recovery, as well as a gel for alertness, concentration, and energy;

[0069] Office workers – In this case, the gel has been formulated to improve concentration and endurance;

[0070] Shift workers - In this case, the gel is formulated to trigger the melatonin pathway to regulate the circadian rhythm, while also providing nutrients and antioxidants to help the brain and muscles recover;

[0071] Underground workers - In this case, the gel has been formulated to assist with the physical demands of the work, improve alertness, endurance, and resilience, while compensating for the lack of sunlight with vitamin D;

[0072] Travelers - In this case, the gel has been formulated to relieve travel-related stress, fatigue, and jet lag, while assisting in regulating the circadian rhythm;

[0073] Athletes - In this case, the gel has been formulated to increase energy, focus, alertness, and reaction time, so that people can perform at their best from the start of a competition or workout;

[0074] Elderly people – In this case, a gel has been designed to trigger curcumin-based pathways to improve memory and brain function, while other nutrients focus on joints, bones, and vision;

[0075] Drivers - In this case, the gel has been formulated to enhance brain cell function and assist with the body's needs during long trips. It increases alertness and endurance, while compensating for the lack of sunlight with vitamin D.

[0076] Obviously, this is merely an example of a group of benefits of easy-to-take gel products because they can contain multiple health ingredients in a relatively small volume (usually less than 50 ml, preferably about 30 - 40 ml).

[0077] Other examples include adding stimulants (such as caffeine), developing products to help with sleep, address hangovers, improve sexual performance, etc.

[0078] In a third embodiment, the dosage form contains health ingredients that target providing dietary replacement.

[0079] In this embodiment, in addition to vitamins and minerals, attention is also paid to delivering especially carbohydrates, proteins, and fats.

[0080] In this and other embodiments, it is desirable to ensure that the gel contains a sufficient and effective amount of the required ingredients. Generally, the gels of the present invention attempt to provide the recommended daily intake (RDI) of one or more ingredients or at least a significant proportion thereof, such as 33% (one-third dose), 50% (half dose), or in some cases 100% of the full daily dose. Alternatively, this amount can be referred to as the adequate intake (AI).

[0081] This data is listed in Tables 1 to 4 below, where the RDI or AI of key components are listed by group, gender, and age.

[0082] Table 1 provides figures for protein and dietary fat;

[0083] Table 2 provides figures for carbohydrates, dietary fiber, and water;

[0084] Tables 3a, b, and c provide figures for vitamins; and

[0085] Tables 4a, b, and c provide the figures for minerals: protein and dietary fat - Table 1

[0086]

[0087] Carbohydrates, dietary fiber, and water – Table 2

[0088]

[0089] Vitamins – Table 3a

[0090]

[0091] Vitamins – Table 3b

[0092]

[0093] Vitamins – Table 3c

[0094]

[0095] Minerals - Table 4a

[0096]

[0097] Minerals – Table 4b

[0098]

[0099] Minerals – Table 4c

[0100]

[0101] Protein optionally includes: milk protein concentrate, whey protein concentrate, soy protein isolate, and sodium caseinate, which may additionally include amino acids, such as one or more of the following: L-glutamine, L-glycine, L-leucine, L-isoleucine, L-valine, β-alanine, L-arginine, and taurine.

[0102] Carbohydrates optionally include, for example: maltodextrin, inulin, fructose, and glucose syrup.

[0103] Dietary fat optionally includes: vegetable fats and oils, fish oil, coconut oil, glycerol monoesters and diesters of fatty acids, and lecithin.

[0104] The vitamins optionally include: vitamin C (ascorbic acid), vitamin K (menadione-7), vitamin E (dl-α-tocopheryl acetate), niacin (nicotinamide), vitamin A (retinyl acetate), pantothenic acid (D-calcium pantothenate), D-biotin, folic acid, vitamin D (cholecalciferol), vitamin B6 (pyridoxine hydrochloride), riboflavin (riboflavin 5'-phosphate sodium), thiamine (thiamine hydrochloride), vitamin B12 (cyanocobalamin), creatine monohydrate, β-carotene, lutein, lycopene oleoresin, choline chloride, L-carnitine, nicotinamide, D-calcium pantothenate, riboflavin, pyridoxine hydrochloride, pteroylmonoglutamic acid, vitamin K1 (phytomenadione), resveratrol, α-ketoglutaric acid, calcium hydroxy methylbutyrate (HMB), tri-creatine malate.

[0105] The minerals optionally include essential minerals and trace mineral sources and salts, such as one or more of the following: tripotassium citrate, sodium chloride, trisodium citrate, magnesium oxide, zinc gluconate, iron fumarate, manganese gluconate, copper gluconate, potassium iodide, sodium molybdate, chromium picolinate, sodium selenite, chromium chloride, potassium iodide, sodium fluoride, sodium chloride, potassium chloride, calcium hydroxide, sodium ascorbate, potassium hydroxide, magnesium hydroxide, ferrous lactate, zinc sulfate, manganese sulfate, and phosphates such as one or more of sodium tripolyphosphate, tricalcium phosphate, potassium phosphate.

[0106] Other components may include:

[0107] Antioxidants, such as one or more of the following: ascorbyl palmitate, α-tocopherol.

[0108] pH regulators, such as one or more of the following: citric acid and ascorbic acid, and

[0109] Flavoring agents and sweeteners.

[0110] Therefore, the gel can be used for disaster relief, dropped into the air or otherwise delivered to where it is needed.

[0111] Typically, these gel packages will be produced in larger volumes, sized up to 250 ml, but more typically 75 ml to 150 ml, and will contain a quarter to half of the recommended daily intake of key nutrients such as protein, carbohydrates, and dietary fat, as well as optionally other key vitamins and minerals as listed in the reference table above.

[0112] Alternatively, it is possible to produce minimal or special nutritional intakes to support weight loss and special dietary / nutritional products, which are produced for elite athletes or fitness users who seek, for example, low-carbohydrate or high-protein products, pre / post workout products or any variants thereof, in particular products that contain carbohydrates, proteins and / or fats in given combinations and relative amounts.

[0113] As previously mentioned, the preferred gels can be used as delivery vehicles to deliver water-soluble ingredients, water-insoluble ingredients and lipids.

[0114] In a fourth embodiment, the gels of the present invention are used to deliver ingredients in the form of entrapped stable emulsions.

[0115] Typically under stirring, a lipid component, such as omega 3 or a water-insoluble vitamin, is emulsified with water and then gelled. Additional emulsifiers can be added prior to gelling to facilitate emulsification.

[0116] Typical food-grade or pharmaceutical-grade emulsifiers are added, such as lecithin, monoglycerides of fatty acids and esters of monoglycerides and diglycerides of fatty acids.

[0117] In a fifth embodiment, the gels of the present invention are used to deliver ingredients in the form of stable solid particle suspensions or dispersions.

[0118] Preferably, the solid particles are nanoparticles (greater than 1 nanometer and less than 1 micrometer).

[0119] In a sixth embodiment, the gels of the present invention are used to deliver ingredients in solution form.

[0120] Of course, in a seventh embodiment, and a particularly preferred embodiment, the oral dosage forms of the present invention can be used to combine health ingredients from any combination of the fourth, fifth and sixth aspects into a single dosage form.

[0121] Advantageously, the present invention allows for the delivery of a large number of different nutrients (e.g., greater than 500 mg) in a user-friendly form, in which case pills and capsules may be impossible or impractical, or would be undesirably large. In addition, the present invention allows for the formulation of liquid nutrients that are not sufficiently stable in water alone but are stable in gel form. Therefore, it is particularly advantageous to provide multiphase combinations. For example, ingredients can be more stable in the solid phase as suspensions or dispersions or as oil-in-water emulsions. The formed solidified gel can capture and immobilize the multiphase, enhancing stability and, for example, masking taste. The solidified gel is easily sheared during delivery to form a new wet interface, thus facilitating delivery.

[0122] By combining two functionally different gelling agents, the applicant has obtained a novel, strong and robust gel platform that can deliver a variety of health ingredients and has improved properties such as improved ingredient loading, taste masking, versatility, etc., and by trapping them in a robust gel, a shearing action is generated during delivery and ingestion, making the product very easy to swallow and overcoming the problem of dysphagia.

[0123] The formulation has a firm jelly form in its stored state and is stable at room temperature, but when sucked or otherwise subjected to a gentle force, shear generates a new wet interface that is easy to swallow. Due to the moisture within the structure, the resulting gel interfaces are inherently wet, and thus their slipperiness makes swallowing easy.

[0124] Unlike known viscous paste-like gel formulations, the solidified robust gels leave a minimal amount of residue other than a water film, making them much easier to swallow as solidified gels than other solid / semi-solid forms. The novel formulation of the present invention can be flavored to further enhance taste masking.

[0125] The novel formulation provides a chemically and physically stable matrix that can be used to entrap water-soluble components, water-insoluble lipids, fat-soluble components, etc.

[0126] As a result of entrapment, contact with the surface of taste buds is reduced. Different from viscous paste-like gels, the gels of the present invention provide a minimal amount of residue other than displacing water, and because the solidified jelly will shear during sucking, the gels of the present invention are very easy to swallow compared to alternative plastic (not elastic) solid / semi-solid forms.

[0127] Advantageously, because they shear, they rapidly release components even at high doses and do so in the context of taste masking.

[0128] Unlike tablets or capsules, the platform has a high degree of flexibility in allowing different health ingredients to be provided in a single dosage form, which is superior to currently available alternatives.

[0129] These products, such as glucose products for addressing hypoglycemic episodes, can be used in conjunction with wearable devices and digital support programs to improve health management. Thus, the products can be used with digital applications and wearable devices (such as Fitbit) so that subjects can better manage their conditions, such as diabetes, by tracking, for example, symptoms and metrics as well as the medications / supplements taken. This provides better information to the subjects, enhances compliance, and improves clinical / health outcomes.

[0130] Advantageously, the present invention allows delivery in a form that does not require a separate beverage, unlike tablets or capsules that require drinking a beverage to aid swallowing, and unlike most sports gels, which are better described as thick pastes and require additional fluid due to the taste of the pasty residue.

[0131] The presence of alginate means that some beneficial calcium salts are incorporated as part of the gelling process. Thus, for formulations targeted at bone health, calcium and / or magnesium salts (such as calcium citrate or carbonate) will contribute to gelation through complexation. Calcium citrate can also enhance the flavor. Calcium bicarbonate can cause effervescence, which can provide an attractive taste.

[0132] The solid suspension can include nanomilled materials, such as curcumin or glucosamine, in a form that enhances their bioavailability.

[0133] While agar and locust bean gum solidify well, their appearance is not attractive. Agar and xanthan gum provide a clearer gel, without color spots. However, agar and alginate gels are most preferred because they appear visually very clear, but more importantly, the alginate crosslinking bonds provide a structured gel that has a different gelling mechanism from non-ionic gel polymers of carbohydrates, improving versatility and performance.

[0134] However, the addition of calcium, magnesium, and zinc salts, such as chlorides or citrates, interferes with the solidification of agar and some other gum polymers. Therefore, to obtain good solidification results, agar and alginate should be used in a specific ratio (w / w). A preferred ratio favors an excess of agar relative to alginate, so the preferred ratio of agar to alginate is from 8:1 to 1:1, more preferably from 5:1 to 1:1, and most preferably about 3:1. Agar is used as an emulsifier and gelling agent, while alginate forms a structured gel with metal 2+ ions (Ca2+, Mg2+, Zn2+), counteracting the effect of these ions when only agar is present.

[0135] Both agar and alginate are suitable for strict vegetarians, vegans, and most religious diets, while gelatin is not suitable because it is an animal protein, usually obtained from pigs.

[0136] The advantage of the combination of agar and alginate gels is that they are less sensitive to temperature effects than other gelling agents. They are also less affected by components (such as oil) that may inhibit gelation, pH changes, and high concentrations of complex carbohydrates (such as maltodextrin). Agar and alginate gels also tend to solidify faster, which is an advantage in manufacturing, contributing to faster and more stable production.

[0137] The lipids used to implement the present invention include any suitable food-grade oils of animal or plant origin. Non-limiting examples include: corn oil, olive oil, sunflower oil, coconut oil, and fish or algal oil. Fish oil and algal oil are particularly advantageous as sources of omega-3, especially DHA and EPA, both of which are important dietary components. The lipid material may advantageously include lipid vitamins, such as any one of vitamin D or vitamin E.

[0138] Flavoring components may be included. Any food-grade flavoring can be used, such as fruits, including lemon, lime, orange, passion fruit, or herbs, or mint or rose water. Flavored oils, such as coconut oil, can also be used.

[0139] In addition - the adaptation of animal species such as pets, farm animals, or other domesticated animals to veterinary products is a challenge because it can be very challenging for animal caregivers to ensure that animals consume oral delivery in the form of tablets, capsules, or powders.

[0140] Benefits can also be provided to improve the compliance of veterinary products.

[0141] The benefits of the present invention include:

[0142] · Taste masking: The gels of the present invention make it possible to mask any mixture of nutrients and the worst, strongest, and unpleasant tastes, such as bitterness, sweetness, fish oil, curcumin (spice / pepper).

[0143] · A large number of nutrients can be formulated into an easily consumable dosage form: Multiple ingredients and large doses can be combined in a single dosage form.

[0144] · Overcomes the choking risk caused by large tablets: Swallowing the gel is much easier than swallowing a tablet. This form helps to solve all swallowing problems, whether it is young children, the elderly, or just those with swallowing difficulties.

[0145] · Quick-acting or targeted delivery: The solidified gel enables the rapid release of relevant nutrients in the relevant parts of the digestive system. Even at large doses, they can act quickly - for example, glucose can be rapidly released in response to a hypoglycemic event.

[0146] · Stable at room temperature. The gel properties provide stability without the need for refrigeration.

[0147] · Contains water as an ingredient. The presence of "locked" but "releasable" water also ensures hydration, and no additional fluid is required for the product to be swallowed. This also helps with digestion and provides an improved taste.

[0148] Brief Description of the Drawings

[0149] Embodiments of the present invention will be further described hereinafter with reference to the accompanying drawings, wherein:

[0150] Figure 1 is an illustration of the dispersed dosage form of the present invention. DETAILED DESCRIPTION OF THE INVENTION

[0152] The preferred base gel (25 ml) comprises agar and alginate as listed in Table 5 below, and various health or well-being promoting ingredients (not shown), in particular nutritional ingredients, are added to the base gel:

[0153] Table 5

[0154]

[0155] Note – Weights are scaled proportionally to the required formulation volume, provided here relative to 25 mL of water.

[0156] The pH is adjusted to a pH of about 5.0. This is within the stable pH range for the main gelling agent, agar.

[0157] Calcium ascorbate can be replaced by an equal amount of calcium citrate or other divalent anion salts.

[0158] It should be understood that this specific example is merely exemplary, and the ingredients and their respective amounts will vary depending on the health ingredients to be added, as illustrated in Examples 2 - 8.

[0159] The general method for preparing the gel preparation is listed in Example 1 below:

[0160] Example 1

[0161] First, any water-soluble ingredients are dissolved in food-grade water. These may include nutritional ingredients such as glucose, as well as preservatives and dilute acids (for pH control). Exemplary preservatives are potassium sorbate, and exemplary pH control agents are weak acids such as citric acid, ascorbic acid, acetic acid, or dilute HCl.

[0162] To facilitate the effective addition of one or more gelling agents, the solution is preferably stirred and heated to near boiling. Agar and sodium alginate are added slowly so that they hydrate gradually with continuous stirring to ensure satisfactory dispersion or dissolution. The dispersion or solution is maintained at the boiling point or near the boiling point for 4 - 5 minutes, sufficient to ensure proper hydration, especially of agar. It is then filled into sachets and cooled to form a firm gel.

[0163] The sachets can be as Figure 1This is illustrated by way of example. The sachet (1) is formed from, for example, plastic or foil layers which are sealed together around an edge (3) which bears a filling and dispensing aperture, including a stopper (4), a nozzle (5) and a lid (6). The sachet is filled through the nozzle (5) and capped with a lid (6) which may be fitted with a frangible seal. In use, the subject removes the lid and drinks the gel by squeezing from the sachet (1) into the nozzle (5) and / or by sucking.

[0164] When preparing the gel, it is desirable to limit the heating time to minimize water loss by evaporation, since excessive evaporation can cause product changes.

[0165] Preferably, agar is used at a concentration of from 0.001 g (1 mg) to 0.02 g (20 mg) per gram of water. More preferably from 0.005 g (5 mg) to 0.01 mg (10 mg) per gram of water, and most preferably from 0.006 g (6 mg) to 0.009 g (9 mg) per gram (equivalent to 1 ml) of water.

[0166] Preferably, alginate is used at a concentration of from 0.0005 g (0.5 mg) to 0.01 g (10 mg) per gram of water. More preferably from 0.001 g (1 mg) to (0.008 g (8 mg) per gram of water, and most preferably from 0.001 g (1 mg) to 0.005 g (5 mg) per gram of water.

[0167] A divalent ion source is added to enhance the formation of the alginate gel. Suitable components include calcium, zinc and / or magnesium salts. For example, calcium citrate, magnesium citrate or zinc citrate are good forms of soluble salts and can also provide a mineral supplement. However, other salts may be used.

[0168] While hot, any lipid component can be added and allowed or encouraged to promote the formation of a suitable emulsion. Generally, the lipid level can be added at a concentration of from 0.1 to 10% w / w of water. More preferably from 1% to 5% w / w of water, and most preferably from 3 mg to 5 mg per gram of water.

[0169] A mechanical homogenizer, such as a Silverson homogenizer, is advantageously used to promote the formation of the emulsion. Any known food grade emulsifier can be added to improve the emulsion quality and physical stability, such as lecithin. Preferably, the emulsifier is of non-animal origin, such as soy lecithin rather than egg lecithin.

[0170] In an advantageous method, the emulsion can be made into a separate cold water mixture precursor and mixed with a separate hot agar-alginate in water precursor (appropriately separating the water) to accelerate cooling and gel formation.

[0171] Other components of the solid suspension can be dispersed into the aqueous composition. When the nutritional ingredient is neither water-soluble nor lipid-soluble, it can be made into a suspension suspended in lipids or water. It is advantageous if the component is ground to a fine particle size, as this can improve suspension stability and also improve bioavailability. Advantageously, the insoluble component can be ground under wet or dry conditions and can be ball-milled, or media-milled or nano-milled or ground in a high-shear homogenizer. The grinding can be carried out in the presence of grinding aids such as leucine, sodium dodecyl sulfate, and metal stearates.

[0172] After heating, the liquid formulation can be metered hot into the desired container and allowed to solidify into a gel.

[0173] More specifically, for example, for a hypoglycemic product, the following work is carried out during the manufacturing process:

[0174] Adjust the pH - ideally to 4 - 6, most preferably about 5. This is within the stable pH range of the main gelling agent agar.

[0175] Typically, the ratio of HCl∶water is 0.80∶100.00 mL. For example, if 40 mL of water is added to the gel, then 0.32 mL of 0.1 M HCl is also added. If HCl is not allowed for commercial production, other organic acids such as citric acid or acetic acid are selected.

[0176] The gel production process involves the following:

[0177] Weigh the non-gelling agents (such as glucose, sorbic acid, water) in appropriate proportions and add them to a suitable mixing container in the order of, for example, the desired glucose (or other carbohydrate), the necessary sorbic acid or other preservative, and food-grade water. Add hydrochloric acid (or alternative acid) to the container using a suitable dispenser.

[0178] Carry out stable stirring. For example, at the laboratory scale, this is a magnetic stir bar. Cover to minimize evaporation and moisture loss.

[0179] Pre-weigh the specified nutrients required for the composition. Mix these non-gelling ingredients while heating the contents of the container. Add one nutrient to the container at a time, allowing it to fully disperse and dissolve, and then add the next nutrient. After all the nutrients have been added, mix for another 2 - 3 minutes.

[0180] Pre-weigh the gelling agents (agar and sodium alginate).

[0181] When all the gelling agents have been added, stir for another 2 - 3 minutes to ensure that all the incorporated gelling agents are no longer visible. When using insoluble ingredients, use a homogenizer to incorporate them.

[0182] In the case of using an oil / lipid component, after immediately removing the heating and before cooling, an oil / lipid material is added and mechanically emulsified using a homogenizer to a suitable milky appearance.

[0183] Allow the formulation to cool and gel.

[0184] The Bloom test is used to characterize the resulting solidified gel grade. Preferably, a Bloom grade of at least 80, up to 90, 100, 110, 120, 130, and 140 is obtained.

[0185] Preferably, a Bloom grade of less than 250, less than 220, less than 200 to less than 180 is obtained.

[0186] The desired optimal Bloom grade is 140 to 180.

[0187] In a preferred embodiment, the present invention provides a unique platform for delivering multiple health components by using two gelling agents with different gelling mechanisms, in particular agar and alginate. The use of an ionic gelling agent counteracts the gel inhibition effect that different health components (such as oils, divalent ions, polysaccharides) may have on a carbohydrate gelling agent (such as agar).

[0188] With reference to some exemplary formulations, this enhanced gel platform, which is the subject of the second aspect of the present invention, is further illustrated. The formulations particularly relate to the third to fifth aspects of the present invention.

[0189] Many formulations address hypoglycemic events. The following variants (Examples 2 to 5) have been confirmed to contain multiple additives in addition to glucose, including multiple examples that include the addition of lipids, water-insoluble vitamins, trace elements, and minerals.

[0190] Example 2

[0191] Special gel for children with hypoglycemia, as shown in Table 6.

[0192] Table 6

[0193]

[0194] Table 6.1 Sub-dispersion B1

[0195]

[0196] Example 3

[0197] Basic adult hypoglycemia gel, as shown in Table 7 Table 7

[0198]

[0199] Example 4

[0200] Hypoglycemic gel for pregnant women, as shown in Table 8 Table 8

[0201]

[0202] Table 8.1 Sub-dispersion B2

[0203]

[0204] Example 5

[0205] Hypoglycemic gel for the elderly, as shown in Table 9 Table 9

[0206]

[0207] Table 9.1 Sub-dispersion B2

[0208]

[0209] In addition to the examples with glucose, many examples illustrating the fourth aspect of the present invention were prepared. The following variants (Examples 6 and 7) are illustrative examples:

[0210] Example 6

[0211] Travel (before flight) gel preparation, as shown in Table 10

[0212] Table 10

[0213]

[0214]

[0215] Example 7

[0216] Travel (after flight) gel preparation, as shown in Table 11

[0217]

[0218]

[0219] Example 8

[0220] The dietary replacement gel designed for remote areas or disaster relief is illustrated with reference to Table 12.

[0221] Basic gel composition (scaled according to the added nutrients)

[0222] Table 12. Basic gel composition

[0223]

[0224] The following groups of nutritional components were introduced into the basic gel:

[0225] A protein, optionally comprising one or more of the following: milk protein concentrate, whey protein concentrate, soy protein isolate, sodium caseinate, in an amount sufficient to meet the minimum RDI or a percentage thereof, such as 50% (twice a day) or 33% (three times a day), and amino acids, optionally comprising one or more of the following: L-glutamine, L-glycine, L-leucine, L-isoleucine, L-valine, β-alanine, L-arginine, and taurine.

[0226] Carbohydrates and sugars, optionally comprising one or more of the following: maltodextrin, inulin, fructose, and glucose syrup, in an amount sufficient to meet the minimum RDI or a percentage thereof, such as 50% (twice a day) or 33% (three times a day).

[0227] Dietary fats, optionally comprising one or more of the following: vegetable fats and oils, fish oil, coconut oil, monoglycerides and diglycerides of fatty acids, and lecithin, in an amount sufficient to meet the minimum RDI or a percentage thereof, such as 50% (twice a day) or 33% (three times a day).

[0228] In addition to these three core energy-providing groups, the product may also contain one or more essential nutrients selected from the following groups:

[0229] Vitamins optionally include one or more of the following: vitamin C (ascorbic acid), vitamin K (menadione-7), vitamin E (dl-α-tocopheryl acetate), niacin (nicotinamide), vitamin A (retinyl acetate), pantothenic acid (calcium D-pantothenate), D-biotin, folic acid, vitamin D (cholecalciferol), vitamin B6 (pyridoxine hydrochloride), riboflavin (riboflavin 5'-phosphate sodium), thiamine (thiamine hydrochloride), vitamin B12 (cyanocobalamin), creatine monohydrate, β-carotene, lutein, lycopene oleoresin, choline chloride, L-carnitine, nicotinamide, calcium D-pantothenate, riboflavin, pyridoxine hydrochloride, pteroylmonoglutamic acid, vitamin K1 (phytomenadione), resveratrol, α-ketoglutaric acid, calcium β-hydroxy β-methylbutyrate (HMB), and creatine malate; and

[0230] Essential minerals, sources and salts, optionally including one or more of the following: tripotassium citrate, sodium chloride, trisodium citrate, magnesium oxide, zinc gluconate, iron fumarate, manganese gluconate, copper gluconate, potassium iodide, sodium molybdate, chromium picolinate, sodium selenite, chromium chloride, potassium iodide, sodium fluoride, sodium chloride, potassium chloride, calcium hydroxide, sodium ascorbate, potassium hydroxide, magnesium hydroxide, ferrous lactate, zinc sulfate, and manganese sulfate and phosphates, optionally including: sodium tripolyphosphate, tricalcium phosphate and potassium phosphate.

[0231] These additional optional ingredients may further include:

[0232] Antioxidants, optionally including ascorbyl palmitate and α-tocopherol.

[0233] Flavoring agents and sweeteners, as well as pH regulators, such as: citric acid or ascorbic acid.

[0234] It should be understood that skilled dietitians will be able to use their general skills and knowledge to formulate the various variations described above to address various needs, including the preparation of complete meal formulas for adults, children, and infants, and Example 8 is only intended to reflect the possibilities available to those skilled in the art.

Claims

1. An oral dosage form, except for a 50 g or 75 g dose of glucose, allows for the combination and formulation of two or more large doses of healthy ingredients selected from water-soluble, water-insoluble, and / or lipid-based ingredients in a single dosage form, which is a drinkable gel with a volume of 25 milliliters to 250 milliliters, wherein the healthy ingredients are retained in a delivery system that comprises: ● Water, ● A gelling agent, which is a polymer gelling agent that gels non-ionically with carbohydrates and a polymer gelling agent that gels with polyvalent ions, ● A divalent cation, and ● A pH regulator wherein the polymer gelling agent that gels non-ionically with carbohydrates is an agarose-based polymer gelling agent, present in an amount of 1 mg to 20 mg per gram of water, the polymer gelling agent that gels with polyvalent ions is an alginate-based polymer gelling agent, present in an amount of 0.5 mg to 10 mg per gram of water, and the agarose-based polymer gelling agent and the alginate-based polymer gelling agent are present in a ratio of 5:1 to more than 1:1 and in an amount that ensures the hydration and formation of a firm gel with a Bloom grade of 100 to 250, and which does not exhibit plastic behavior under stress but rather exhibits elasticity under stress until the failure point, at which point the structure of the gel ruptures or shears, irreversibly creating new interfaces, making it more fluid upon ingestion, and thus it is a drinkable gel, The pH range of this dosage form is from 4 to 6.

2. The dosage form according to claim 1, wherein the agarose-based polymer gelling agent and the alginate-based polymer gelling agent are present in a ratio of 3:1 to more than 1:

1.

3. The dosage form according to any one of the preceding claims, which further comprises one or more preservatives.

4. The dosage form according to claim 3, wherein the preservative is sorbic acid.

5. The dosage form according to any one of the preceding claims, which comprises one or more water-soluble healthy ingredients.

6. The dosage form according to claim 5, wherein the one or more water-soluble healthy ingredients are selected from the group consisting of or including water-soluble vitamins, carbohydrates, sugars, and amino acids.

7. The dosage form according to any one of the preceding claims, which comprises one or more water-insoluble healthy ingredients.

8. The dosage form according to claim 7, wherein the one or more water-insoluble healthy ingredients are selected from the group consisting of or including healthy ingredients that form a dispersion or suspension.

9. The dosage form according to claim 8, wherein the healthy ingredients that form a dispersion or suspension are selected from the group consisting of or including water-insoluble trace elements, proteins, minerals, and plant extracts such as curcumin.

10. The dosage form according to any one of the preceding claims, which comprises one or more fat-soluble healthy ingredients.

11. The dosage form according to claim 10, wherein the one or more fat-soluble healthy ingredients are selected from the group consisting of or including oils, especially fish oil and algal oil, DHA, EPA, and fat-soluble vitamins D and E.

12. The dosage form according to claim 11, which comprises a gelled emulsion.

13. The dosage form according to any one of claims 10 to 12, further comprises an emulsifier.

14. The dosage form according to any one of claims 1 to 6, which comprises 1 g to 40 g of glucose in a gel volume of less than 250 ml.

15. The dosage form according to claim 14, which further comprises one or more of carbohydrates, proteins, fats, vitamins, minerals, lipids, trace elements and plant extracts.

16. The dosage form according to any one of claims 1 to 4, which comprises a dietary substitute that contains at least one-third of the recommended daily intake of protein, carbohydrates and fat.

17. The dosage form according to any one of claim 16, which contains at least one-third of the recommended daily intake of protein, carbohydrates and / or fat.

18. The dosage form according to any one of claims 16 or 17, which contains at least half of the recommended daily intake of protein, carbohydrates and / or fat.

19. The dosage form according to any one of claims 16 to 18, which contains the recommended daily intake of protein, carbohydrates and / or fat in a single dose.

20. The dosage form according to any one of the preceding claims, which is packaged in a sachet (1) having a spout (5) or a straw, so as to facilitate the ingestion of the gel preparation by squeezing and / or sucking.

21. A method of delivering a combination of high doses of two or more health components selected from water-soluble, water-insoluble and / or lipid-based components, the method comprising ingesting the dosage form according to any one of claims 1 to 19 by squeezing and / or sucking the drinkable gel from the package according to claim 20.

Images