Foaming composition containing apoiquorin

Abstract

To provide novel and alternative compositions for alleviating or preventing calcium imbalance. [Solution] The present invention generally relates to compositions useful for maintaining calcium homeostasis. Specifically, the present invention relates to an apoiquorin-containing effervescent composition useful for preventing and / or alleviating diseases or symptoms related to calcium imbalance. Certain embodiments of the present invention further include at least one stimulant (e.g., caffeine) and / or vitamin D.

Description

Technical Field

[0001] <Statement Regarding Research or Development Sponsored by the Federal Government> None. <Cross - Reference to Related Applications>

[0002] This application claims the benefit of U.S. Provisional Patent Application No. 63 / 068,084 (filed on August 20, 2020), and the entire disclosure thereof is incorporated herein by reference. to be included. shall be

[0003] The present invention generally relates to compositions useful for maintaining calcium homeostasis. The present invention specifically relates to an apoquercetin - containing foaming composition useful for the prevention and / or alleviation of diseases or conditions associated with calcium imbalance.

Background Art

[0004] Calcium is the fifth most abundant element in the human body and is mainly present in bones. More than 99% of the calcium in the body is stored in the skeleton, and the skeleton constantly exchanges its supply with the remaining less than 1% of calcium dissolved in body fluids such as blood and soft tissues. Most of the control of this exchange is largely dependent on the endocrine system, which senses the concentration of ionized calcium in plasma and instructs calcium exchange to maintain this critical balance. Among the 1% of calcium in interstitial fluid and soft tissues, the proportion that ionizes to become soluble is very small. The less than 1% of calcium in body fluids and tissues binds to proteins, especially calcium - binding proteins (CaBP). CaBP is known to function in maintaining calcium homeostasis. ​​​​​​​​​​The concentration of calcium ions required for a living organism to carry out necessary physiological processes is specific. Therefore, maintaining calcium homeostasis is extremely important for physical health. So, what is the appropriate concentration of calcium ions in plasma and body fluids for nerve excitability, muscle contraction, membrane permeability, It is understood to be important for bodily functions, including cell division, hormone secretion, and bone mineralization. However, bodily functions are not limited to these. The breakdown of calcium homeostasis, i.e., calcium Muin balance is associated with many diseases, symptoms, and conditions, including cancer, heart disease, and neurodegenerative diseases. While related, the diseases, syndromes, and conditions are not limited to these.

[0006] Traditionally, calcium channel blockade has been used to block the flow of calcium between the inside of cells and the interstitial fluid. The medication is used to prevent calcium-related diseases, including hypertension, angina, asthma, migraines, and neuropathy. Although these have been widely prescribed as useful pharmaceuticals, calcium-related disorders are not limited to these. For example, nimodipine can alleviate calcium imbalances that cause nerve deterioration in dementia. This has been shown to improve clinical symptoms and cognitive function. However, the above Many calcium channel blockers can cause fatigue, fluid retention, heartburn, and irregular heart rate. Unwanted side effects include dizziness, stomach upset, and, rarely, fainting, fever, and excessive bleeding. However, side effects are not limited to these.

[0007] Despite the above advances, novel and alternative methods for alleviating or preventing calcium imbalances are needed. The composition is still necessary. In particular, there is a need for pharmaceutical or nutritional supplement compositions that have reduced side effects compared to conventional drugs, If such a composition were discovered, it would fulfill a long-desired requirement in the medical and nutritional health fields. This will likely be in line with the request.

[0008] Furthermore, the above-mentioned pharmaceutical or nutritional supplement composition is not suitable for people of any age, and in any way... It must be administered even to people with a healthy level of health, which can often be difficult. Patients may hesitate to swallow pills, tablets, capsules, or other solid medication formulations. This often occurs, especially when the individual has problems with swallowing. For example, Swallowing difficulties can be caused by globus hystericus or choking resulting from problems with pharyngeal or esophageal motility. This often causes pain and aversion to swallowing the compound. Furthermore, it can lead to pharyngitis and / or other problems. If the pharynx is significantly swollen due to bacterial infection or other serious irritation, It is often difficult and / or impossible for patients to swallow pharmaceutical formulations in this form. The size, shape and taste of the pharmaceutical compound, the psychological aversion to oral ingestion, and / or the distribution Due to a personal choice not to swallow compounded substances, there are situations where one hesitates to orally ingest pharmaceutical compounds. There are also cases where this is a problem. In this respect, young patients are particularly at risk. However, if they receive guidance on how to administer medication... Patients requiring the therapeutic active ingredient in the formulation may take or administer the prescribed dose themselves. It must be taken. Therefore, it contains formulations to address calcium imbalance. There is a continuing request for a better method to administer a therapeutically effective amount of the composition. It exists in a specific way. [Overview of the Initiative]

[0009] This invention enables overall improvement of the subject's physical and mental health compared to conventional compositions and methods. It offers various advantages.

[0010] The first aspect of the present invention relates to a foaming tablet supplement for treating symptoms or diseases related to calcium imbalance. Such a treatment method involves administering a foaming tablet containing an effective amount of apoquercetin, a foaming pair containing an acidic component and an alkaline component. The acidic component can be citric acid, tartaric acid, malic acid, fumaric acid, adipic acid, succinic acid, or a salt thereof, and the alkaline component can be sodium bicarbonate, sodium hydrogen carbonate, sesquicarbonate of sodium, potassium carbonate, potassium bicarbonate, sesquicarbonate of potassium, magnesium carbonate, sodium glycine bicarbonate, L-lysine carbonate, arginine carbonate, amorphous calcium carbonate, ammonium carbonate, or ammonium bicarbonate. In one embodiment, the supplement can further contain at least one stimulant, and the stimulant can be caffeine, yerba mate, ephedrine, guarana or carrot.

[0011] In still another embodiment of the present invention, the supplement can also contain vitamin D. Vitamin D can be D3 cholecalciferol. In another aspect of the present invention, a therapeutic foaming composition can be used for treating symptoms or diseases related to calcium imbalance. The therapeutic foaming composition contains an effective amount of apoquercetin, an effective amount of vitamin D, at least one stimulant,

[0012] and a foaming system containing at least one acid and at least one alkaline compound. The at least one acidic component can be citric acid, tartaric acid, malic acid, fumaric acid, adipic acid, succinic acid, or a salt thereof. The at least one alkaline component is carbon The at least one acidic component can be citric acid, tartaric acid, malic acid, fumaric acid, adipic acid, succinic acid, or a salt thereof. The at least one alkaline component can be sodium bicarbonate, sodium hydrogen carbonate, sesquicarbonate of sodium, potassium carbonate, potassium bicarbonate, sesquicarbonate of potassium, magnesium carbonate, sodium glycine bicarbonate, L-lysine carbonate, arginine carbonate, amorphous calcium carbonate, ammonium carbonate, or ammonium bicarbonate. The at least one acidic component can be citric acid, tartaric acid, malic acid, fumaric acid, adipic acid, succinic acid, or a salt thereof. The at least one alkaline component is carbon Sodium oxyhydrogen, sodium bicarbonate, sodium sesquicarbonate, potassium carbonate, heavy carbon Potassium acid, potassium sesquicarbonate, magnesium carbonate, sodium glycine bicarbonate, L - Lysine carbonate, arginine carbonate, amorphous calcium carbonate, ammonium carbonate, or heavy carbon It can be ammonium acid. The at least one stimulant is caffeine, y It can be mala mate, ephedrine, guarana, or ginseng. Vitamin D is D3 It can be converted to cholecalciferol.

[0013] In yet another aspect of the present invention, the treatment of symptoms or diseases related to calcium imbalance The method for placement involves applying the above-mentioned apoiquorin and other compounds to the target requiring treatment. This includes administering a therapeutic effervescent composition or supplement, provided that the apoiquorin It is not administered together with its cofactor, coelenterazine. Related to calcium imbalance. Symptoms or disorders that are related to sleep, energy, mood, pain, or memory It can be a symptom or a disease. By administering apoiqualin, the target sleep Quality, energy quality, or mood quality improves, or pain is relieved, or memory is altered. The improvement is suggested by an improvement in scores on standard cognitive assessments. Symptoms or disorders related to muin balance may also include nerve excitability, muscle contraction, membrane permeability, and cellular activity. Symptoms or diseases related to cell division, hormone secretion, osteomineralization, or ischemia-induced cell death. This can be achieved, and the symptoms or disease improve when apoiquorin is administered. Liment or effervescent composition may cause any of the above symptoms or diseases related to calcium imbalance. It can also be used to treat illnesses. Supplements or effervescent compositions are drugs and It can be used in this way.

[0014] Considering the present specification and claims, other subjects, features and advantages of the present invention will become clear. It will become that way. [Modes for carrying out the invention]

[0015] I. General Overview Before describing the materials and methods of the present invention, it should be noted that the present invention is subject to various modifications, and therefore will not be described here. It is understood that this is not limited to specific methods or materials used. The terminology and usage described herein are used solely for the purpose of describing specific embodiments. This is not intended to limit the scope of the invention, and the scope of the invention is limited to the appended claims. It should be understood that it is limited only by the enclosure.

[0016] The terms "a, an" and "the" in this specification and the attached claims. The singular form of "to" includes the plural form unless the context clearly indicates otherwise. It should be noted that the usage differs between "one (a, an)", "one or more", and "at least one". The words may also be replaceable in this specification. In addition, "equipment," "includes," and "have" It should be noted that the term "ru" may also be replaceable.

[0017] Unless otherwise defined, all technical and scientific terms used in this application refer to the invention. It has the same meaning as that which is usually understood by someone with ordinary knowledge in the field. In carrying out or testing the present invention, all methods and materials similar to or equivalent to those described in this application may be used. The following methods and materials can be used, but preferred methods and materials will be described below. All publications and patents specifically mentioned in the application are publications usable in this invention. All reports, including descriptions and disclosures of chemical substances, equipment, statistical analyses, and methods. For the purposes of this application, references are incorporated into the description of this application. All references used should be considered as indicators of the level of technology in the field in question. All matters described herein are prior to the disclosures of the prior inventions. This should not be interpreted as an admission that it should not be recognized as having been done.

[0018] II. The present invention Aequolin is a bioluminescent protein originally isolated from bioluminescent jellyfish and other marine organisms. The aquorin complex consists of a 22,285 dalton apoiquorin protein and molecular acid It contains the element and the luminescent group coelenterazine. This complex contains 3 Ca lf- Ions bond Then, coelenterazine oxidizes to coelenteramide, and at the same time releases carbon dioxide. It emits blue light. Aequorin is not released or secreted from cells, Furthermore, it is not compartmentalized or isolated within the cell. Therefore, over a relatively long period of time, C a 2+ Aequorin measurements have been used to detect changes. In multiple experimental systems, Aequorin luminescence was detected several hours to several days after cell loading. Furthermore, aequorin luminescence was detected in the cells. It is also known that it does not inhibit function or embryonic growth.

[0019] The aequorin complex is Ca 2÷ Due to dependent luminescence, intracellular Ca 2+ Widely used as an indicator It has been used. Specifically, Aequorea victoriae is used for the following purposes (1) to (4) Used for: (1) Individual choline-affinity cells of the adrenal gland to nicotinic cholinergic agonists (2) To analyze the secretion response of Ca during myocardial injury 2+ An eye to clarify the role of release (3) Ca at fertilization 2+ (4) During development Sarcoplasmic reticulum Ca in chick myoblasts 2÷ The purpose is to investigate the adjustment of pump pressure, (5) Note The purpose is to calibrate a micropipette with a small capacity of approximately 3 picoliters.

[0020] The molecular weight of apoiqualin is approximately 22 kDa. It can be used to regenerate aequorin by reducing disulfide bonds. Calcium-loaded apoequolin reacts with unreacted luminescent proteins to which the substrate is bound. It has the same intricate scaffolding and the same overall folding pattern.

[0021] Traditionally, purifying aequorin from the jellyfish Aequorea victoria required extraction work in a laboratory. However, the refined product was quite heterogeneous or toxic to the organisms being studied. This sometimes happened. The purified bioluminescent protein obtained from 2 tons of jellyfish is typically about 1 It is 25 mg. In contrast, recombinant aequorin is preferably genetically modified intestinal Apoiquorin was purified from bacteria, and then ionized in vitro with high-purity coelenterazine. It is produced by reforming the complex. Apoiquorin useful in the present invention is described. It is commercially available by purification methods and / or synthesis known to those skilled in the art. are. S. Inouye, S. Zenno, Y. Sakaki, and F. Tsuji. High level expression and (1991) Protein Expression and Purification 2, 122-1 26.

[0022] This invention aims to correct or maintain the calcium balance of a target by applying apoiqua to the target. This relates to the administration of a phosphorus-containing effervescent composition. Maintaining sodium concentration is important for nerve excitability, muscle contraction, membrane permeability, cell division, hormone secretion, and bone mineralization. It is thought to be important for a wide variety of bodily functions, including chemical processes and the prevention of cell death after ischemia. However, such bodily functions are not limited to these. Collapse of calcium homeostasis In other words, calcium imbalance causes many diseases, symptoms and conditions and / or It is thought that these diseases, symptoms, and conditions are related to sleep quality and energy. This includes quality, mood quality, memory quality, and pain perception. According to research on CaBP... CaBP acts as a protective factor in maintaining appropriate ionized calcium levels. It was recognized that this was the case.

[0023] The present invention further relates to the administration of an apoiquorin-containing effervescent composition. A preferred embodiment The apoiquorin-containing effervescent composition further comprises at least one stimulant. Non-specific examples of a single type of stimulant include caffeine, yerba mate, ephedrine, and ga. Lana and carrots may be included. In yet another preferred embodiment, apoiquorin may be included. The effervescent composition may further contain vitamin D. In yet another embodiment, A suitable embodiment of an apoiquorin-containing effervescent composition includes at least one stimulant and a vitamin Includes both D.

[0024] Vitamin D increases the intestinal absorption of calcium, iron, magnesium, phosphates, and zinc. It is a group of lipid-soluble secosteroids. Vitamin D is produced when the skin is exposed to ultraviolet rays from sunlight. It is produced in the body through various means. Vitamin D can also be obtained naturally from sources such as fish, fish liver oil, and egg yolks. It is found in existing foods, as well as in fortified dairy products and grains. The two most common forms of vitamin D are vitamin D3 (cholecalciferol). These are vitamin D2 (ergocalciferol) and vitamin D2.

[0025] Vitamin D is a physiologically inactive fat-soluble vitamin and requires two activations in the body. It must be hydroxylated. The first hydroxylation takes place in the liver, and vitamin D 25-hydroxyvitamin D[25(O], also known as "calcifediol"] Converted to H)D. The second hydroxylation mainly takes place in the kidneys, resulting in "calcitriol Also known as "biologically active 1,25-dihydroxyvitamin D[1,25(OH It forms [2D]. This active form of vitamin D, calcitriol, is a hormone. It circulates in the bloodstream, regulating the concentration of calcium and phosphate in the blood, and supporting normal bone growth. Promote reconstruction.

[0026] Vitamin D promotes calcium absorption and enables normal mineralization of bones, thus reducing calcium levels. Maintain adequate serum calcium and phosphate levels to prevent umtetany. Vitamin D is also used in bone growth and bone reconstruction by osteoblasts and osteoclasts. Min D is also involved in cell growth, regulation of neuromuscular and immune function, and reduction of inflammation. That is what we know.

[0027] A preferred formulation of the present invention modifies the target calcium balance and vitamin D level or To maintain this condition, the subject is administered an effervescent composition containing apoiquorin and vitamin D. This concerns the following: Vitamin D deficiency can be a contributing factor to calcium imbalance. Maintaining ionized calcium concentrations in plasma and body fluids is important for nerve excitability, muscle contraction, membrane permeability, A wide variety of processes, including cell division, hormone secretion, bone mineralization, and prevention of cell death after ischemia. These are considered important for bodily functions, but such bodily functions are not limited to these. The breakdown of calcium homeostasis, or calcium imbalance, is associated with many diseases and symptoms. These diseases, symptoms, and conditions are thought to cause and / or be associated with the following: The state includes aspects related to sleep quality, energy quality, mood quality, memory quality, and pain perception. It is included. Research on CaBP has shown that CaBP helps maintain appropriate ionized calcium levels. It was recognized that this acts as a protective factor.

[0028] Maintaining vitamin D levels is important for calcium absorption, cell growth, and the regulation of neuromuscular and immune function. Furthermore, it is considered important for reducing inflammation. Vitamin D deficiency is associated with the proper mineralization of bone tissue. It is most closely associated with rickets, a disease that does not progress to metastasis, and can lead to bone softening and skeletal deformities. (US Medical Research) The guidelines recommend a diet rich in vitamin D to maximize bone health. The Recommended Daily Allowance (RDA) is 600 international units (IU) for adults aged 1 to 70 years, and for adults over 70 years. It is set at 800 IU.

[0029] Therefore, in a particular embodiment, the method of the present invention is for treating calcium imbalance. To slow the progression of calcium imbalance, and to prevent the onset of calcium imbalance. Therefore, and for the activity to prevent and / or treat the recurrence of calcium imbalance. The ingredients include apoiquorin (and optionally vitamin D and / or at least one other). The present invention includes administering a stimulant (such as a known therapeutic agent) in an effervescent formulation. In other embodiments, the present invention relates to known therapeutic agents. Apoiquorin is foamed together with one or more additional active substances that have therapeutic or nutritional function values. The present invention provides a method including administration in a sexually active formulation. Particularly preferred uses of apoiqualin include sleep One or more symptoms and conditions related to the quality of sleep, energy, mood, memory, and pain perception. It is a procedure.

[0030] In this specification, the term "treatment" includes both preventive treatment and disease remission treatment. The terms "reduction," "mitigation," "suppression," and "inhibition" as used in the application specification mean becoming smaller or It has the commonly understood meaning of decreasing. The term "progress" as used in this specification means This refers to an increase, progression, growth, or worsening of the scope or severity. In this specification, "relapse" refers to this increase or progression. The term refers to a recovery after remission from a disease.

[0031] In this specification, the term "administration" means administering a patient, tissue, organ, or cell to apoiqualin. It refers to bringing into contact with something. In this specification, "administration" means in vitro, i.e., in a test tube. It can be performed, or in vivo, that is, within the cells or tissues of living organisms such as humans. It can be done. In a preferred embodiment, the above-mentioned inventions that can be used in the present invention This includes administering a foaming compound or composition to a patient or subject. "Patient" or "Subject" Although used equivalently in this application, (1) treatment is possible by administering apoiqualin. Or having a treatable calcium imbalance-related disorder, or (2) apoiqua Mammals susceptible to calcium imbalance-related diseases preventable by phosphorus administration, It generally refers to a human being.

[0032] The terms "effective dose" or "therapeutically effective dose" as used in this specification refer to a dose that is toxic, irritating, or allergenic. Sufficient to obtain the desired therapeutic response without causing excessively harmful side effects such as dysphagia. This refers to the amount of the active substance. The specific "effective amount" depends on the specific condition being treated, the patient's physical condition, and the treatment. The type of animal receiving treatment, the duration of the procedure, and the nature of any concurrent treatments (if any). , and factors such as the specific formulation used, and the structure of the compound or its derivative It is clear that things will change. In this case, (1) Calcium imbalance-related diseases (1) Prevention of (2) Reversal or stabilization of calcium imbalance-related disorders, or both. The amount that achieves this is considered the "therapeutically effective amount." The optimal effective amount is determined by a person skilled in the art using normal practice. It can be easily identified through experimentation.

[0033] In specific preferred effervescent formulations for oral administration to the target, apoiquorin is approximately 10 m It is included in pharmaceutical formulations at a dose of g / dose, and the recommended dose for the target group is approximately 10 mg / day. (That is, one capsule per day). Other suitable apoiquorin-containing oral medications. In the case of effervescent formulations, the composition or formulation further contains at least one stimulant.

[0034] To improve the probability of ingestion and / or absorption of the active pharmaceutical ingredient, the pharmaceutical formulation includes a foaming agent. The material can be used. The compound or composition may be, for example, a tablet, powder, capsule, or pellet. It can be formed into a solid, and this solid is further mixed with an aqueous excipient before oral ingestion. The compositions that can be administered according to the present invention can be processed by known dissolution, mixing, granulation, or tablet formation processes. It can be prepared in this way. For oral administration, apoiquorin or its physiologically permitted Derivatives that are accepted, such as salts, esters, N-oxides, etc., are commonly used for this purpose. It is mixed with additives such as excipients, stabilizers, and inert diluents, and then mixed using conventional methods. Suitable forms for administration, such as tablets, coated tablets, hard or soft gelatin capsules. It is converted into an aqueous solution, an alcohol solution, or an oil solution, etc. The compound is, for example, a water-based food or It is contained in water-based excipients for beverages, etc., and can be stirred or mixed, and the water-based excipient is For example, it contains a minimum amount of water, such as at least approximately 0.1 ml. The excipients are selected by the caregiver. Alternatively, it may be selected by the patient, or simply put into the patient's mouth when taken directly. This may be saliva and / or other water-containing liquids. Foaming compounds are added to the excipients. When this occurs, gas is generated, and this gas causes foaming, which leads to the disintegration of the compound in the excipient. The active pharmaceutical ingredient is released when the drug is administered. Excipients are used depending on the patient. It is taken orally.

[0035] The term "foaming" generally refers to the release of gas from a liquid or mixture (Hawley's C Chemical Dictionary, pp. 432 onwards, 2001). Therefore, the term "foaming" as used in this specification refers to "foaming." The term "compound" generally refers to a compound containing one or more gases under appropriate conditions, such as contact with water. This refers to a composition or mixture of components that produce sap.

[0036] In this specification, the term "aqueous excipient" means a medium or carrier containing at least a minimum amount of water. This refers to the body, for example, food, etc. Therefore, water-based excipients should be small-water-containing excipients that contain a small amount of water. It can be used as an excipient containing a large amount of water.

[0037] As used in this specification, the term "food" refers to safe and consumable liquids, semi-solids, or solid whole foods. It refers to all substances. Therefore, food contains all substances that can be consumed by mammals of all species and ages. This includes all beverages and food.

[0038] To form effervescent formulations containing apoiquorin, for example, tablets, powders, or capsules can be used. The formulation can be included in an inert excipient such as pellets. Examples include conventional tablet bases such as lactose, sucrose, or corn starch, and acacia, corn Binders such as cornstarch and gelatin, or cornstarch, potato starch, and argy Disintegrants such as nitrates, or lubricants such as stearic acid or magnesium stearate, It is a combination of things.

[0039] Examples of suitable oil-based excipients or solvents include, for example, vegetable oils such as sunflower oil or fish liver oil, or animal oils. The composition can be in the form of dry granules or wet granules. For example, There is a sterile liquid such as water or oil, which contains surfactants and other pharmaceutically acceptable adjuvants. These are products with added ingredients, or products without them. Examples of oils include petroleum and animal oil. These include oils, vegetable oils, or synthetic oils, such as peanut oil, soybean oil, or mineral oil. Generally, water, saline solution, hydrated glucose and related sugar solutions, and, for example, propylene Glycols such as polyethylene glycol or other glycols are suitable liquid carriers.

[0040] The gas that produces foam is mostly carbon dioxide, and this carbon dioxide reacts with acids and bases. This is derived from the fact that foaming systems or foaming pairs typically consist of at least one acid and a small amount of It contains at least one type of alkaline compound. Therefore, effervescent tablets contain (1) an active ingredient and (2) an acid. (3) an alkali compound, consisting of at least three components.

[0041] Many acidic and basic components are known to react in the presence of water to produce gases. For example, citric acid, tartaric acid, malic acid, fumaric acid, adipic acid, succinic acid, and other acids and multiple acids The combination reacts with carbonates or carbonate sources in water to produce CO2 gas. Acids include, but are not limited to, food acids, anhydrides, and acidic salts. Examples include citric acid, tartaric acid, malic acid, fumaric acid, adipic acid, succinic acid, etc. The anhydrides of the above acids are generally used as anhydrides that decompose in the presence of water to produce reactive acids. It can be used. Acidic salts generally dissociate in water or in the water content of aqueous excipients to react with acid species. It generates. Examples of suitable acidic salts include sodium dihydrogen phosphate and disodium dihydrogen pyrophosphate. This includes, but is not limited to, um, acidic citrate, and sodium bisulfite. The overall solubility of an acid or its source varies individually and specifically, and is the domain of those skilled in the art. If so, it will be obvious. The effectiveness of the acid in gas generation and the amount of gas generated are generally determined by the effervescent distribution. It depends on the water solubility of the acidic form in the compound.

[0042] Suitable carbonate sources include, for example, sodium, potassium, lithium, calcium, and magnesium. This includes dry solid carbonates, bicarbonates, and sesquibicarbonates of metals such as um, but these are limited. This is not an enumeration. Examples of appropriate carbonates include sodium bicarbonate, sodium hydrogen carbonate, and cereal. Sodium sodium carbonate, potassium carbonate, potassium bicarbonate, potassium sesquicarbonate, magnesium carbonate Cium, sodium glycine bicarbonate, L-lysine carbonate, arginine carbonate, and amorphous Calcium carbonate is included, but this is not an exhaustive list. Ammonium carbonate and bicarbonate are also included. Monium is also a suitable carbonate. In addition, the above are basic components included in the formulation. Any combination of carbonate sources can also be used. Due to an excess of basic components... Furthermore, a basic excipient and / or a basic oral environment is provided, and taste masking properties are achieved. The benefits include the provision of [this] and numerous other advantages. An example of a foaming agent is... In pharmaceutical formulations, gaseous foaming components generally make up about 5% to 85% of the total weight of the composition. It must.

[0043] The composition of the effervescent tablet may also contain a lubricant, which is preferably used to form a clear solution. For this purpose, it is selected from water-soluble compounds. Examples of such lubricants include sodium benzoate. Sodium acetate, fumaric acid, polyethylene glycol (PEG) 4000+, alanine, Glycine is one example.

[0044] Diluents, ligands, buffers, sweeteners, flavorings, colorants, solubilizers, disintegrants, wetting agents, and so Other commonly used excipients and conventional excipients can be added to the formulation. Appropriate fragrance The ingredients include natural and artificial fragrances, such as mint like peppermint and menthol, and artificial vanilla. Flavorings such as cinnamon and various fruit flavorings are possible, and these flavorings can be used alone or in combination. It is used. Fragrances are generally used in amounts that vary according to each individual's preference, for example, in the final composition The amount can be in the range of approximately 0.5% to approximately 3% of the object's weight.

[0045] When using sweeteners, the present invention includes both natural and artificial sweeteners. This may include sweeteners that are well known in the field. Therefore, the additional sweeteners may be the following: You can choose from these, but the following examples of sweeteners are not an exhaustive list: for example, sucrose, gluco Sugars such as corn syrup, invert sugar, fructose, and mixtures thereof, saccharin, and For example, various salts of saccharin such as sodium salt or calcium salt, cyclamic acid, and For example, various salts of cyclamic acid such as sodium salts, and dipeptides such as aspartame. Sweeteners, dihydrochalcone, glycyrrhizin, stevia (stevioside), and, for example sugar alcohols such as sorbitol, sorbitol syrup, mannitol, and xylitol Additionally, as an additional sweetener, non-fermentable sugars as described in U.S. Patent RE26,959 are available. A substitute (hydrolyzed starch) is a possible alternative. Also, German Patent No. 2001,0 The synthetic sweetener described in Specification No. 17.7 is 3,6-dihydro-6-methyl-1-1-2,3- Oxathiazine-4-one-2,2-dioxide, especially potassium (acesulfame-K) The sodium and calcium salts can also be used. Generally, the amount of sweetener is the amount of sweetener It varies depending on the type and the desired taste of the final product. For example, the amount of natural sweetener used is approximately 5% by weight. While this can extend to as much as [amount missing], the amount of artificial sweeteners used can be as low as approximately 1% by weight.

[0046] The colorants usable in this invention include, for example, pigments such as titanium dioxide. The pigment can be included in an amount of up to approximately 1% by weight, preferably up to approximately 0.6% by weight. The colorants are other dyes suitable for food, drugs, and cosmetics, and are known as FD&C dyes, etc. It may also contain other dyes. The materials acceptable for the wide range of applications described above are: Preferably, it is a water-soluble material. For example, an ink known as FD&C Blue No. 2. It contains a digoid dye, which is the disodium salt of 5,5'-indigotine disulfonic acid. Yes, it exists. Also, the dye known as FD&C Green No. 1 is a triphenylmethane dye. Includes, 4-[4-N ethyl-p-sulfobenzylamino]diphenylmethylene][1-( N-ethyl-Np-sulfonium benzyl)-2,5-cyclohexadienimine It is a thorium salt. All FD&C and D&C dyes and their chemical structures are described. The text is from Kirk-Othmer Encyclopedia of Chemical Technology, in Volume 5, pp. 857-858. As it is described on page 84, the contents described therein are included in the disclosure of this application by reference. Let's assume that.

[0047] The pharmaceutical composition further includes a liquid or a composition that has been dried by lyophilization or other means. It can also be used as a diluent for various buffering components (e.g., Tris-HCl, acetate, phosphate). (etc.), pH and ionic strength, additives to prevent absorption to the surface, for example, albumin or This includes gelatin and other cleaning agents (e.g., Tween® 20, Tween® 8) 0, Pluronic® F68, bile salts, etc.), solubilizer (e.g., glycerol) (e.g., polyethylene glycerol), antioxidants (e.g., ascorbic acid, sodium metabisulfite) Thorium, etc.), preservatives (e.g., thimerosal, benzyl alcohol, parabens, etc.), bulking agents. Agents or tonicity modifiers (e.g., lactose, mannitol, etc.), covalent bonds of multiple polymers, e.g. For example, covalent bonding between polyethylene glycol and protein, complex formation with metal ions, or For example, specific polymer compounds such as polylactic acid, polyglycolic acid, or hydrogels are used as materials. Incorporating ingredients, or liposomes, microemulsions, micelles, lamellar compounds Incorporate materials into multilamellar vesicles, red blood cell ghosts, or spheroplasts. This may include: physical state, solubility, stability, and in vivo release. It affects the rate and in vivo clearance rate. Release control The composition or sustained-release composition contains lipophilic depot agents (e.g., fatty acids, waxes, oils, etc.) This includes the contents that were included.

[0048] For example, polyethylene glycol, polyethylene glycol and polypropylene glycol Copolymer of cellulose, carboxymethylcellulose, dextran, polyvinyl alcohol, Modified by covalent bonding of water-soluble polymers such as livinylpyrrolidone or polyproline The half-life in the blood after intravenous injection of the chemical substance is significantly longer than that of the corresponding compound in its unmodified state. It is known to be long. Such modifications improve the solubility of the chemical substance in aqueous solution. This eliminates aggregation, improves the physical and chemical stability of the compound, and enhances the immunogenicity and reactivity of the compound. Responsiveness can be significantly reduced. As a result, the polymer described above is more effective than the unmodified material. The frequency or amount of substance abduction is reduced, thereby achieving the desired result. In vivo bioactivity can be achieved.

[0049] The preparation of compositions containing active ingredients is well known in the art. The active ingredient is mixed with excipients that are pharmaceutically acceptable and compatible with the active ingredient. This is often the case. Suitable excipients include, for example, water, saline solution, glucose, glycerol, and Examples include ethanol, etc., or combinations thereof. The composition further includes the active ingredient It may also contain small amounts of auxiliary substances that enhance its effectiveness, such as humectants, emulsifiers, and pH buffers. can.

[0050] The effervescent composition may contain the active ingredient in the form of a pharmaceutically acceptable salt in a neutralized state. Yes, it is possible. Pharmaceutically acceptable salts include acid addition salts, which are, for example, hydrochloric acid or ricomethic acid. Formed using inorganic acids such as acetic acid, or organic acids such as acetic acid, tartaric acid, or mandelic acid. Salts formed from free carboxyl groups include, for example, sodium, potassium, and ammonium. It can also be obtained from inorganic bases such as monoium, calcium, or ferric hydroxide. Alternatively, for example, isopropylamine, trimethylamine, 2-ethylaminoethanol, It can also be derived from organic bases such as stidine and procaine.

[0051] The salt of apoiqualin is preferably a pharmaceutically acceptable salt, but other salts may also be used in the present invention. It may be used in the preparation of foaming compositions or pharmaceutically acceptable salts thereof. Appropriate pharmaceutical The above acceptable salts include acid addition salts, such as hydrochloric acid, sulfuric acid, and methanesulfuric acid. Fumaric acid, fumaric acid, maleic acid, succinic acid, acetic acid, benzoic acid, oxalic acid, citric acid, tartaric acid Mix a pharmaceutically acceptable acid solution, such as an acid, carbonic acid, or phosphoric acid, with a solution of apoiqualin. It can be formed by doing so.

[0052] Furthermore, the apoiquorin-containing effervescent composition described in this specification is a nutritional functional food It can also be provided in the form of a food composition, and this nutritional functional food composition is ApoiQuali It prevents the onset of various harmful calcium imbalance-related disorders, or reduces such disorders. It reduces or stabilizes. In this specification, "nutritional functional food" or " The term "nutritional functional food composition" refers to a medical health composition that includes the prevention and / or treatment of diseases. This refers to food or a part of food that provides lit. The nutritional functional food composition of the present invention contains an active ingredient and The only component included may be apoiqualin, or alternatively, the nutrition of the present invention Functional food compositions further include the total intake of vitamins, coenzymes, minerals, herbs, amino acids, etc. Dietary supplements containing the above-mentioned substances are used to supplement meals by increasing the amount of nutrients in the diet. It can be mixed with to.

[0053] Therefore, the present invention is a method for providing nutritional functional benefits to patients, and apoiqualin The present invention provides a method comprising the step of administering to a patient a nutritional functional food effervescent composition containing the following: Yes. Such compositions generally include "a carrier acceptable for nutritional functional foods," and in this application, "Nutritionally functional food carriers" include the above-mentioned pharmaceutically acceptable carriers suitable for oral use. This refers to all carriers suitable for oral administration. Therefore, the present invention relates to a patient who was unable to take oral medication. A better mechanism for orally administering drugs to patients using a simpler and more patient-friendly medium than before. It provides a sensibility.

[0054] In certain embodiments, the effervescent nutritional supplement composition of the present invention includes a dietary supplement. Functionally defined, this dietary supplement is an immune booster, anti-inflammatory agent, antioxidant, and anti- This includes antiviral agents, or combinations thereof.

[0055] Immunogenetics and / or antiviral agents are used to promote wound healing and improve immune function. It is used as an immune booster and antiviral agent, and contains corn flower extract and echinacea herbs. Contains extracts of herbs from the genus Astragalus, or goldenseal. Astragalus is an effective immune-boosting agent, whether in its natural or processed state. It stimulates the development of stem cells in the bone marrow and active immune cells in lymphoid tissue. Zinc and its biological activity Salts of zinc, such as zinc gluconate and zinc acetate, also act as immune-boosting agents in the treatment of the common cold. do.

[0056] One example of an antioxidant is allicin, a naturally occurring sulfur-containing amino acid, which is an antioxidant in the blood. It has the effect of raising the level of chemical enzymes. Herbs or herbal extracts containing allicin, for example Garlic and other similar substances are also effective antioxidants. Catechins and green tea containing catechins are also effective antioxidants. Extracts from the Astragalus genus are also effective antioxidants. Extracts from the Astragalus genus also exhibit antioxidant activity. Bioflavonoids such as cetin, hesperidin, rutin, and mixtures thereof also have antioxidant properties. It is effective as a drug. The main beneficial role of bioflavonoids is that they are effective in the body as vitamin C This may prevent oxidation. This allows more vitamin C or as This allows the body to utilize corbic acid.

[0057] Bioflavonoids such as quercetin are also effective anti-inflammatory agents, and the present invention can be used as such. It can be used in finished products. It can also be used in anti-inflammatory herbal supplements, or in plants or herbs. The anti-inflammatory component obtained from can be used as an anti-inflammatory agent in the composition of the present invention. These supplements and anti-inflammatory ingredients include the protein contained in pineapple. Bromelain, a dehydrogenase; nettle tea and extract; turmeric; turmeric extract; or One example is curcumin, a yellow pigment isolated from corn.

[0058] Another supplement that can be used in this invention is derived from herbs of the ginger genus. Ginger is made up of compounds such as gingerol and related compounds such as scutellaria. It is known to have a cardiotonic effect when combined with ugaol, and is also used to treat dizziness and vestibular disorders. It has advantages in terms of placement. Furthermore, ginger is also effective in treating nausea and stomach disorders. .

[0059] Compositions for treating pain in arthritis and other joint diseases include soft tissue reconstruction, particularly soft tissue Supplements that aid in bone regeneration are useful. Glucosamine, glucosamine sulfate, Chondroitin is found in various species such as elk velvet antler. It can be obtained from sources. Marine lipid complexes, omega-3 fatty acid complexes, and fish oil are also available. It is known to be useful in treating pain associated with arthritis.

[0060] Supplements that are effective in treating migraines include feverfew and ginkgo. The main active ingredient in tiger frutescens is sesquiterpene lactone parthenolide, which is used to treat vasospasm in blood vessels. It inhibits the secretion of prostaglandins, which cause pain through activity. Feverfew also has anti-inflammatory properties. It exhibits symptomatic properties. Fish oil is useful in treating migraines due to its platelet-stabilizing and antivasospasmodic effects. It is possible. Ginkgo biloba herb can also be used to treat migraines by stabilizing arteries and improving blood circulation. To assist.

[0061] The pharmaceutical effects of some of the supplements listed above have been explained, but in this invention, other supplements It is also possible to use Liment, and its effectiveness has been sufficiently demonstrated in scientific literature. ru.

[0062] The present invention can be better understood by considering the following non-limiting examples.

[0063] Examples Example 1 This embodiment describes a particularly preferred apoiquorin-containing composition, and this composition It contains 13.8 mg of apoiquarin and 27.8 mg of vitamin D3 (cholecalcifero). (L) 100,000 IU / g dried caffeine, 135 mg anhydrous caffeine granules EP, and 50 0mg sorbitol BP, 417 xylitol DC, and 80mg corn starch It contains 2 mg of riboflavin 5-phosphate sodium and 45 mg of saccharin sodium B P, 250 mg (nat) orange flavoring, 40 mg beet powder, and 1450 mg Contains anhydrous citric acid and 1040 mg of sodium bicarbonate. Xylitol DC The ingredients include xylitol and sodium carboxymethylcellulose. Vitamin D3 The ingredients are sucrose, acacia, corn starch, medium-chain triglycerides, and silicon dioxide. Contains (nat) orange flavoring ingredients, vitamin D3, and DL-α-tocopherol. The ingredients are maltodextrin, a fragrance preparation, silicon dioxide, natural fragrance substances, and vitamins. It contains E. The beet powder ingredients are concentrated beet root juice, maltodextrin, and citric acid. It contains [ingredients]. The total weight of the tablets is 4000 mg. [Table 1]

Claims

1. Effervescent tablet supplements for treating symptoms or diseases related to calcium imbalance It is a nt, The foaming pair comprises an effective amount of apoiquorin and an acidic component and an alkaline component. A supplement that features these characteristics.

2. Furthermore, it includes at least one stimulant, The supplement according to claim 1.

3. The aforementioned at least one stimulant is caffeine, yerba mate, ephedrine, or guarana. Or selected from carrots. The supplement according to claim 2.

4. The aforementioned acidic components include citric acid, tartaric acid, malic acid, fumaric acid, adipic acid, succinic acid, and These are selected from these salts. A supplement according to any one of claims 1 to 3.

5. The aforementioned alkaline components are sodium bicarbonate, sodium hydrogen carbonate, and sodium sesquicarbonate. Potassium carbonate, potassium bicarbonate, potassium sesquicarbonate, magnesium carbonate, glycerin Sodium bicarbonate, L-lysine carbonate, arginine carbonate, amorphous calcium carbonate, carbon Selected from ammonium ammonium acid or ammonium bicarbonate. A supplement according to any one of claims 1 to 4.

6. Furthermore, it contains vitamin D, A supplement according to any one of claims 1 to 5.

7. The aforementioned vitamin D is D3 cholecalciferol. The supplement according to claim 6.

8. Therapeutic effervescent composition for treating symptoms or diseases related to calcium imbalance And, An effective amount of apoiqualin, An effective amount of vitamin D, At least one type of stimulant, A foaming system comprising at least one acid and at least one alkali compound, A therapeutic effervescent composition characterized by containing the following:

9. The aforementioned at least one acidic component is citric acid, tartaric acid, malic acid, fumaric acid, adipine Acids, succinic acid, or selected salts thereof, The therapeutic foaming composition according to claim 8.

10. The above-mentioned at least one alkaline component is sodium bicarbonate, sodium hydrogen carbonate, Sodium sesquicarbonate, potassium carbonate, potassium bicarbonate, potassium sesquicarbonate, magnesium carbonate Nesium, glycine sodium bicarbonate, L-lysine carbonate, arginine carbonate, amorphous carbon Selected from calcium carbonate, ammonium carbonate, or ammonium bicarbonate. The therapeutic foaming composition according to claim 8 or 9.

11. The aforementioned at least one stimulant is caffeine, yerba mate, ephedrine, or guarana. Or selected from carrots. A therapeutic effervescent composition according to any one of claims 8 to 10.

12. The aforementioned vitamin D is D3 cholecalciferol. A therapeutic effervescent composition according to any one of claims 8 to 11.

13. A method for treating symptoms or diseases related to calcium imbalance, For the object requiring the above treatment, the apoiqualin according to any one of claims 1 to 12 A therapeutic effervescent composition or supplement containing is administered, provided that the apoiqualin is... It is not administered together with coelenterazine, which is a cofactor of [the drug]. A method characterized by the following:

14. The symptoms or diseases related to the aforementioned calcium imbalance are sleep-related symptoms or diseases. , by administering apoiquorin to the subject, the quality of sleep of the subject is improved. The method according to claim 13.

15. The symptoms or diseases related to the aforementioned calcium imbalance are energy-related symptoms or diseases. Therefore, by administering apoiquorin to the subject, the energy quality of the subject is improved. To be done, The method according to claim 13.

16. The symptoms or disorders related to the aforementioned calcium imbalance are mood-related symptoms or disorders. , by administering apoiquorin to the subject, the mood quality of the subject is improved. The method according to claim 13.

17. The symptoms or diseases related to the aforementioned calcium imbalance are pain-related symptoms or diseases. By administering apoiquorin to the subject, the subject's pain is relieved. The method according to claim 13.

18. The symptoms or diseases related to the aforementioned calcium imbalance are memory-related symptoms or diseases. , by administering apoiquorin to the subject, memory improved, and this improvement in memory, This is suggested by improvements in scores on standard cognitive assessments. The method according to claim 13.

19. Symptoms or diseases related to the aforementioned calcium imbalance include nerve excitability, muscle contraction, and membrane permeability. Symptoms or diseases related to sex, cell division, hormone secretion, osteomineralization, or cell death due to ischemia. The patient The method according to claim 13.

20. Treatment of the sleep quality, energy quality, or mood quality of the subject , relief of pain in the subject, improvement of memory in the subject, or related to calcium imbalance Symptoms or diseases that involve nerve excitability, muscle contraction, membrane permeability, cell division, and hormone secretion. It is used in the treatment of symptoms or diseases related to bone mineralization or cell death due to ischemia. ru, A supplement according to any one of claims 1 to 7.

21. Treatment of the sleep quality, energy quality, or mood quality of the subject , relief of pain in the subject, improvement of memory in the subject, or related to calcium inbalance Symptoms or diseases involving nerve excitability, muscle contraction, membrane permeability, cell division, hormone secretion, bone It is used in the treatment of symptoms or diseases related to mineralization or cell death due to ischemia. The foaming composition according to any one of claims 8 to 12.

22. A supplement according to any one of claims 1 to 7, used as a pharmaceutical drug.

23. A foaming composition according to any one of claims 8 to 12, to be used as a pharmaceutical agent.

Images