KR20140024713A - Composition for calcium uptake comprising mineral water - Google Patents

Abstract

The present invention relates to a composition for calcium uptake which includes mineral water and, more specifically, to a pharmaceutical composition for preventing and treating osteoporosis and to a composition for calcium uptake which includes 200-300 mg/L of potassium, 7000-9500 mg/L of sodium, 1400-1700 mg/L of calcium, 900-1100 mg/L of magnesium, 3-9 mg/L of zinc, 25-35 mg/L of strontium, 200-500 μg/L of selenium, 65-75 μg/L of vanadium, 0.5-1.5 μg/L of germanium, 10-40 μg/L of manganese, 1-3 μg/L of cobalt, 600-950 μg/L of titan, 3-9 μg/L of copper, 0.02-0.09 mg/L of lithium, 16000-19500 mg/L of chlorine ion, 1.5-3.0 mg/L of fluorine ion, 40-56 mg/L of bromide ion, 3000-4500 mg/L of sulfate ion, 0.8-1.2 mg/L of boron, and 0.5-15 mg/L of silicon dioxide as mineral components. The composition including brine mineral water collected from 1100 m underground of hot spring in coastal terrace in Gang-reung-si Ok-gye-myun geum-jin3ri 92-1, Kang-won-do, Korea according to the present invention reduces numerical value of instant parathyroid hormone (iPTH), and increases concentration of ionized calcium in order for the composition of the present invention which includes the effective composition to effectively help calcium absorption into body so that the composition can be effectively used for preventing and treating diseases such as osteoporosis caused by calcium deficiency. [Reference numerals] (AA,DD) Kumjin hot spring; (BB,EE) Calcium + N/S; (CC,FF) Calcium

Description

[Technical Field] The present invention relates to a calcium supplement composition containing mineral water,

The present invention relates to a calcium supplement composition containing mineral water and a pharmaceutical composition for the prevention and treatment of osteoporosis.

Calcium is the most abundant inorganic element in the human body, and about 2% of the body weight of ordinary adults is about 1200g. 99% of the body calcium forms the skeleton and teeth, and the remaining 1% is responsible for the regulation of physiological activities such as contraction and relaxation of muscles, regular heartbeat, blood clotting, activation of enzymes, delivery of intracellular stimuli and excitement .

Calcium is a nutrient with a low bioavailability and does not exceed a maximum of 60%. It is usually estimated that the absorption rate of an adult is about 25 to 30%, and ingesting it in the form of food is the most desirable (Miller GD et al. 2001)

Calcium supplements and calcium enhancers can be used if the food is good enough to consume calcium. At present, natural calcium products such as inorganic calcium salts such as calcium carbonate, calcium citrate, calcium citrate, calcium phosphate, calcium sulfate, calcium lactate and calcium gluconate, and milk calcium, coral calcium, shell calcium, have. However, inorganic calcium-based materials used in the food industry are known to exhibit low bioabsorption rates of up to 40% of their intake. In addition, most of them have toxicity, so they have limitations and difficulties in that they can not use excessive amount to meet the required intake amount and bioavailability (utilization).

In addition, natural calcium is high in bioavailability, but due to high price or hygienic problems, it is not generally utilized as a source of calcium such as food, medicine, feed, fertilizer.

The shortage of calcium intake is associated with the lack of absorption, and as the calcium concentration in the body decreases due to the long-term deficiency of calcium supply, the calcium absorption rate of the small intestine, the increase of the renal calcium resorption and the calcium excretion of the bone are increased, Osteoporosis, and the like.

Therefore, it is necessary to develop a natural substance that can increase calcium absorption in the body without side effects.

Korean Patent No. 0915596 Korea Patent Publication No. 2008-01035287

It is an object of the present invention to provide a calcium supplement composition containing mineral water.

Another object of the present invention is to provide a composition for preventing and treating osteoporosis containing mineral water.

In order to achieve the object of the present invention, the present invention provides a calcium supplement composition containing marine mineral water taken as an active ingredient at 1100 m underground in a hot spring area of coastal monotone area 92-1, Kangjin 3 ridge, Okgye-myeon, Gangneung- do.

In one embodiment of the present invention, the mineral water includes minerals such as potassium 200 to 230 mg / L, sodium 7000 to 9500 mg / L, calcium 1400 to 1700 mg / L, magnesium 900 to 1100 mg / L of manganese, 10 to 40 占 퐂 / L of manganese, 1 to 3 mg / L of manganese, 20 to 35 mg / L of strontium, 200 to 500 mu g / L of chlorine, 16000 to 19500 mg / L of chlorine ions, 1.5 to 3.0 mg / L of fluorine ions, 40 to 90 mg / L of bromine ions, 56 mg / L, sulfuric acid ions 3000 to 4500 mg / L, boron 0.8 to 1.2 mg / L and silicon dioxide 0.5 to 15 mg / L.

In one embodiment of the present invention, the mineral water is a concentrate, and the concentrate may contain 0.5 to 50% (v / v) based on the total weight of the composition.

In one embodiment of the present invention, the mineral water may reduce the level of blood parathyroid hormone (iPTH) and increase the concentration of ionized calcium.

The present invention also provides a pharmaceutical composition for the prevention and treatment of osteoporosis, which comprises marine mineral waters collected at 1100 m underground in a hot spring area of coastal monotone region 92-1, Jinjin 3 ridge, Okgye-myeon, Gangneung-si, Gangwon-do, Korea as an effective ingredient.

In one embodiment of the present invention, the mineral water includes minerals such as potassium 200 to 230 mg / L, sodium 7000 to 9500 mg / L, calcium 1400 to 1700 mg / L, magnesium 900 to 1100 mg / L of manganese, 10 to 40 占 퐂 / L of manganese, 1 to 3 mg / L of manganese, 20 to 35 mg / L of strontium, 200 to 500 mu g / L of chlorine, 16000 to 19500 mg / L of chlorine ions, 1.5 to 3.0 mg / L of fluorine ions, 40 to 90 mg / L of bromine ions, 56 mg / L, sulfuric acid ions 3000 to 4500 mg / L, boron 0.8 to 1.2 mg / L and silicon dioxide 0.5 to 15 mg / L.

In one embodiment of the present invention, the mineral waters are concentrated and concentrated by desalination and evaporation, and the concentrate may contain 0.5 to 50% (v / v) based on the total weight of the composition.

According to the present invention, a composition for supplementing calcium containing marine mineral water taken at 1100 m underground of a hot spring area in a coastal monotone region 92-1, Jinjin 3 ridge, Okgye-myeon, Gangneung-si, Gangwon-do, Korea reduces the level of blood parathyroid hormone (iPTH) The composition of the present invention containing it as an active ingredient can effectively help calcium absorption in the body.

FIG. 1 is a schematic diagram showing the participation state of a subject participating in a clinical experiment according to an embodiment of the present invention.
FIG. 2 is a graph showing the mean plasma concentration of the parathyroid hormone in each group measured on the first day and the last day of the clinical experiment.
FIG. 3 is a graph showing the mean plasma concentrations of ionized calcium in each group measured on the first day and the last day of the clinical experiment.
FIG. 4 is a schematic diagram briefly showing an experimental plan for each day to examine the effect of supplementing calcium hydroxide in a mineral fluid-induced animal model.
FIG. 5 shows the result of x-ray photographing of each group after preparing a bone loss induction animal model.
FIG. 6 shows CT images of each group after preparing a bone loss-inducing animal model.
FIG. 7 is a graph showing the volume of bones in each group.
8 is a graph showing the thicknesses of bones in each group.

The present invention provides a novel calcium supplement composition containing mineral water having an effect of reducing the level of blood parathyroid hormone (iPTH) and increasing the concentration of ionized calcium to promote calcium absorption. The mineral water containing the calcium supplement composition according to the invention as an active ingredient is characterized in that it is a marine mineral water taken from the 1100 m underground of a hot spring area in the coastal monotonous area of 92-1, Kejin 3 rye, Okgye-myeon, Gangneung-si, Gangwon-do, Korea.

In general, seawater is called deep sea water by distinguishing it from surface water. Deep sea water refers to seawater less than 200 meters from the sea surface. It does not cause photosynthesis and contains many inorganic nutrients such as nitrogen, phosphorus and silicate It is known that it is not contaminated by air or chemical substances, and that it is not contaminated by solar and general bacteria, and that physical and chemical cleanliness is also excellent because of a small number of positive bacteria.

In addition, it has low water temperature change at low temperature throughout the year, has stable low water temperature, and contains essential trace elements and various minerals in a balanced manner. .

Therefore, the surface water is not suitable for use in the human body such as food and beverages in the present state of severe marine pollution. However, since deep sea water is not much in number in the surface layer and contains almost no pathogenic organisms, It can be said that the safety is extremely high.

On the other hand, calcium is not only one of the essential nutrients that form bones and teeth, but also plays an important role in the information transfer function of moving the heart or brain, which is directly connected with life. Therefore, lack of calcium and osteoporosis in the body and a variety of abnormalities occur in the body of about 60 trillion of cells in the body can not work and die. The amount of calcium in the blood is always kept constant, which is an important condition for the cell to function normally. Assuming the calcium concentration in the blood to be 10,000, the cell should contain only a tenth of a million calcium.

In other words, the difference in the calcium concentration between the inside and outside of the cell (in the blood) is kept at 1: 1, so that the cell can receive information from outside or transmit information accurately. However, when calcium is insufficient, the balance of concentration difference between 1 and 1 is lost. If you do not take the necessary amount of calcium every day, calcium in the body will be deficient and the calcium concentration in the blood will be lowered. Therefore, calcium supplementation and calcium enhancers can be used if sufficient calcium intake is difficult to achieve through food.

Accordingly, the present inventors have developed a therapeutic agent capable of absorbing calcium in the body using marine mineral water. The inventors of the present invention have developed a therapeutic agent capable of absorbing calcium in the body by using a marine mineral water, which is deep ocean water eluting from the underground 1100 m bedrock of a hot spring area in coastal monotone region 92-1, It was confirmed that the effect of decreasing the level of blood parathyroid hormone (iPTH) and increasing the concentration of ionized calcium is excellent and it is confirmed that the mineral water is very suitable for use as a calcium supplement composition.

Namely, according to one embodiment of the present invention, 24 patients were selected as clinical trial subjects and divided into A, B and C groups for administration of different clinical test substances for one week, and the parathyroid hormone concentration was measured at the first and last days of the clinical experiment As a result, it was found that the parathyroid gland basal ganglia were reduced as much as the B and C groups consumed with the calcium preparation in the group A administered with the mineral water of the present invention (see FIG. 2).

In another embodiment of the present invention, blood samples were collected from the same subjects on the first day and the last day of the clinical experiment and the ionized calcium concentration was measured. As a result, the ionized calcium concentration tended to increase at the last day (See Fig. 3).

The inventors of the present invention confirmed that the mineral water provided by the present invention can lower the levels of parathyroid hormone in the body and increase the concentration of ionized calcium. Thus, ultimately, And that it can be used for the purposes of.

Accordingly, the present invention can provide a calcium supplement composition containing marine mineral water taken as an active ingredient at a depth of 1100 m from a hot spring area in a coastal monotonous area at 92-1, Jinjin 3 ridge, Okgye-myeon, Gangneung-do, Gangwon-do, Korea.

The mineral water contained as an active ingredient in the composition of the present invention contains, as minerals, 200 to 230 mg / L of potassium, 7000 to 9500 mg / L of sodium, 1400 to 1700 mg / L of calcium, 900 to 1100 mg / L of zinc, 25 to 35 mg / L of strontium, 200 to 500 μg / L of selenium, 65 to 75 μg / L of vanadium, 0.5 to 1.5 μg / L of germanium, 10 to 40 μg / 1 to 3 μg / L of titanium, 600 to 950 μg / L of titanium, 3 to 9 μg / L of copper, 0.02 to 0.09 mg / L of lithium, 16000 to 19500 mg / L of chlorine ion, 1.5 to 3.0 mg / Ions of 40 to 56 mg / L, sulfuric acid ions of 3000 to 4500 mg / L, boron of 0.8 to 1.2 mg / L and silicon dioxide of 0.5 to 15 mg / L.

As a result of analyzing the mineral components of the mineral water according to the present invention commissioned by the Korea Institute of Science and Technology (KIST), Korea Basic Science Research Institute (KBSI) and Korea Institute of Geoscience and Mineral Resources (KIGAM) Mineral waters are new and unknown.

In addition, in the present invention, the mineral water may be the marine mineral water itself taken at 1100 m underground of a hot spring area in the coastal area of Gangjin-ri, Gyeonggi-do, Gangneung-si, Gangneung-si, Korea. If the mineral water itself is used, (V / v) to 100% (v / v) based on the total weight of the composition, or in the form of concentrates, when used as a concentrate, 0.5 to 50% (v / v).

The concentrate may be a solid obtained by evaporating, concentrating and drying the mineral water according to the present invention, or may be a concentrate obtained by evaporating the natural mineral water, artificially desalting and drying (or evaporating) the natural mineral water.

Specifically, the concentrate of the mineral water according to the present invention can be produced by the following method. First, the raw water is collected and then filtered. In this case, the filtration step may be performed through several filtration steps. In the present invention, four filtration steps are performed. That is, the first step filtration was performed by removing the suspended matters having a particle size of more than 10 μm. Then, the suspended matters having a particle size of more than 5 μm were filtered out and then filtered. After sterilization by UV, the suspension of more than 0.2um was filtered out by a four step filtration process. The thus-obtained filtrate can be subjected to a desalting step and a drying step, and desalting is not limited thereto, but an electrodialyzer can be used.

Thereafter, the desalted powder is produced through natural drying or drying using a dry drier. In one embodiment of the present invention, a vacuum freeze dryer was used for the drying. In the final step, desalination powder can be pulverized and packaged.

In addition, the concentrate of mineral water according to the present invention can be produced by first concentrating raw water, drying it, and then performing a filtration step.

The composition of the present invention may be used as a pharmaceutical composition having calcium absorption activity. When the mineral water according to the present invention is concentrated and used, it may be contained in an amount of 0.5 to 50% by weight based on the total weight of the composition.

In particular, the pharmaceutical composition containing mineral water according to the present invention can be used as a pharmaceutical composition for preventing and treating osteoporosis.

The human bones continue to undergo constant changes like other body tissues, with old bones being destroyed and new bones being formed. During this turnover, the destruction or bone resorption of old bone is caused by the osteoclast that occurs in the blood cells, which causes pits in the bone to release the calcium in the bone into the blood, Exports, blood clotting, and so on. On the other hand, in contrast to this, bone formation that forms a new bone is a phenomenon in which osteoblasts generated in bone cells fill collagen in osteoclasts by osteoclasts and calcium and phosphorus deposits To make new, hard bones. However, such human bone mineral density tends to decrease with aging, especially in women after menopause, so-called postmenopausal osteoporosis is becoming a serious health problem.

In particular, osteoporosis is a state in which the lime of the bony tissue is reduced and the density of the bone becomes thinner, thereby expanding the bone marrow cavity. As the condition progresses, the bone is weakened, The bone mass is affected by various factors such as genetic factors, nutritional intake, hormonal changes, exercise and lifestyle differences, and the causes of osteoporosis are aging, lack of exercise, low birth weight, smoking, calcium deficiency, menopause, Ablation and the like are known.

Therefore, the composition of the present invention, which can sufficiently supplement calcium in the body, can be used for the purpose of improving, preventing and treating diseases caused by lack of calcium such as osteoporosis.

In addition, the composition according to the present invention may contain a pharmaceutically effective amount of the mineral water itself or the mineral water concentrate according to the present invention, alone or in combination with one or more pharmaceutically acceptable carriers, excipients or diluents. A pharmaceutically effective amount as used herein refers to an amount sufficient to promote absorption of calcium in the body. For example, the pharmaceutically effective amount of the mineral water concentrate according to the present invention is 0.5 to 100 mg / day / kg body weight, preferably 0.5 to 5 mg / day / kg body weight. However, the pharmaceutically effective amount may be appropriately changed depending on the symptom of the disease, the age, body weight, health condition, sex, administration route and treatment period of the patient.

The term "pharmaceutically acceptable" as used herein refers to a composition that is physiologically acceptable and does not normally cause an allergic reaction such as gastrointestinal disorder, dizziness, or the like when administered to humans. Examples of the carrier, excipient and diluent include lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, acacia rubber, alginate, gelatin, calcium phosphate, calcium silicate, cellulose, methylcellulose, Polyvinylpyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate and mineral oil. Further, it may further include a filler, an anticoagulant, a lubricant, a wetting agent, a flavoring agent, an emulsifying agent and an antiseptic agent.

In addition, the calcium absorption-active pharmaceutical composition of the present invention may be formulated using methods known in the art so as to provide rapid, sustained or delayed release of the active ingredient after administration to the mammal. The formulations may be in the form of powders, granules, tablets, emulsions, syrups, aerosols, soft or hard gelatine capsules, sterile injectable solutions, sterile powders.

The composition according to the present invention may be administered through various routes including oral, transdermal, subcutaneous, intravenous or muscular, and the dose of the active ingredient may be varied depending on various factors such as route of administration, age, sex, And the like.

In addition, the composition of the present invention can be administered in combination with a known compound having calcium absorption-promoting activity.

Accordingly, the present invention can provide a calcium absorption aid comprising a composition containing mineral water taken as an active ingredient at 1100 m underground of a hot spring area of the Kumjingri coastal monoculture area.

Furthermore, the composition according to the present invention not only provides a superior calcium absorption activity in the body but also has a higher safety than a conventional chemical preparation using natural deep sea water as a raw material and has no toxicity and side effects to the drug, Can be used.

Therefore, the composition of the present invention can be added to a food containing a large amount of calcium, so that it can be used as a health functional food composition for promoting calcium absorption.

Further, it can be easily utilized as a food containing a large amount of calcium, for example, as a raw material, additives, food additives, functional foods or beverages of foods.

In the present invention, the term " food " means a natural product or a processed product containing one or more nutrients. Preferably, the food is a state in which it can be directly eaten through a certain processing step. Food, food additives, functional foods and beverages.

Foods to which the composition according to the present invention can be added include, for example, various foods, beverages, gums, tea, vitamin complexes, and functional foods. In addition, in the present invention, the food may include special nutritive foods (e.g., crude oil, spirits, baby food, etc.), meat products, fish meat products, tofu, mackerel, noodles (Such as soy sauce, soybean paste, kochujang, mixed potatoes), sauces, confectionery (eg, snacks), candies, chocolate, gums, ice cream, milk products (eg, fermented milk, cheese, But are not limited to, pickled foods (various kinds of kimchi, pickles, etc.), beverages (e.g., fruit drinks, vegetable beverages, beverages, fermented beverages and the like) and natural seasonings (e.g. The food, beverage or food additive may be prepared by a conventional production method.

In addition, the functional food refers to a food group imparted with added value to function and express the function of the food by using physical, biochemical, biotechnological techniques, etc., or to control the biological defense rhythm of the food composition, Means a food which has been designed and processed so as to sufficiently express the body's control function with respect to the living body. Specifically, it may be a health functional food. The functional food may include a food-acceptable food-aid additive, and may further comprise suitable carriers, excipients and diluents conventionally used in the production of functional foods.

In addition, in the present invention, the beverage is a collective term for drinking thirst or for enjoying a taste, and includes a functional beverage. The beverage is not particularly limited to the ingredients other than the above-mentioned calcium supplement composition according to the present invention as an essential ingredient in the indicated ratios and may contain various flavors or natural carbohydrates as an additional ingredient such as ordinary drinks have.

Furthermore, the food containing the composition of the present invention in addition to the above-mentioned composition can be used as a food such as various nutrients, vitamins, minerals (electrolytes), flavors such as synthetic flavors and natural flavors, colorants and fillers (cheese, And carbonates used in alginic acid and its salts, organic acids, protective colloid thickening agents, pH adjusting agents, stabilizers, preservatives, glycerin, alcohols, carbonated drinks, etc., and these components may be used independently or in combination Can be used.

In the food containing the composition of the present invention, the amount of the composition according to the present invention may be 0.001% by weight to 90% by weight, preferably 0.1% by weight to 40% by weight, And in the case of beverages, it may be contained in a proportion of 0.001 g to 2 g, preferably 0.01 g to 0.1 g based on 100 ml. However, in the case of long-term intake for health and hygiene purposes or for health control purposes, And since the active ingredient has no problem in terms of safety, it can be used in an amount of more than the above range, so it is not limited to the above range.

Therefore, the present invention can provide a health functional food having calcium absorption activity containing the mineral water or mineral water concentrate according to the present invention as an active ingredient, and the form of the food is not particularly limited, but powder, granule, Capsule or beverage form.

Hereinafter, the present invention will be described in detail by the following examples. However, the following examples are illustrative of the present invention, and the contents of the present invention are not limited by the following experimental examples.

< Example  1>

The mineral water collecting and collecting method according to the present invention Concentrate  Produce

In order to collect mineral water, the inventors extracted hot spring water taken from a 110m underground rock in the Kangjinri beach coastal area of Gangneung, Gangneung, Gangneung-si, Gangneung-myeon, and filtered by using a line filter of 0.25 micrometer to remove pollutants. Desalting was performed using a dialyzer (voltage: 5.5 to 7.5 V, electrode solution: 3% Na2SO4, CJTTS-2-10 ED, Creation Techno). After the desalination was completed, the precipitate was filtered and dried using a vacuum freeze dryer (temperature: -40 to 30 ° C., degree of vacuum: 5 mTorr). The concentrate of the present invention prepared by this process was subjected to the following experiment Respectively.

< Example  2>

Clinical Experiment of Mineral Water According to the Present Invention

In order to confirm the calcium absorption effect of the mineral water of the present invention according to Example 1, healthy subjects were asked to drink the mineral water of the present invention and to confirm the calcium absorption effect.

The schedule of the clinical trial of the present invention is shown in Table 1 below.

<2-1> Criteria for selection and exclusion of target groups

The subjects of this trial were healthy volunteers who met all the criteria for recruitment through the recruitment notification of clinical trial subjects but did not meet any of the exclusion criteria.

<Selection Criteria>

1. A healthy adult whose age was between 20 and 50 years of age at the time of screening

2. A person weighing less than ± 20% of the ideal body weight, with a weight of 55 kg for males and 45 kg for females. Ideal body weight = (height cm-100) X 0.9

3. After hearing the detailed explanation of this clinical trial, the person who has agreed to voluntarily decide to participate and to make a written agreement

<Exclusion criteria>

1. Those who have suspected acute illness at screening

2. Clinically significant, active adults with cardiovascular, respiratory, renal, endocrine, hematologic, digestive, central nervous, mental, or malignant tumors

3. Persons with hypersensitivity or clinically significant hypersensitivity reactions to drugs or other drugs (aspirin, antibiotics, etc.) containing calcium or the same component

4. Screening of 25 (OH) Vitamin D3 in the range of 4.8 to 52.8 ng / mL

5. A person whose Ca was 8.0 ~ 10.0 mg / dL when screening

6. Those who are found to be inadequate as subjects by a medical examination (history of disease, physical examination, ECG, clinical pathology examination, etc.) within 28 days before the start of test

7. In the case of a vital sign measured at the sitting position after resting for more than 5 minutes, the values included in either standard systolic blood pressure ≥ 140 mmHg or ≤100 mmHg or diastolic blood pressure ≥ 90 mmHg or ≤ 65 mmHg

8. Those with a history of substance abuse

9. Patients with clinically significant allergic disease (other than mild allergic rhinitis that does not require treatment)

10. Within 60 days before the initiation of the trial (administration of the substance for clinical trial) Those who participated in other clinical studies as subjects

11. Within 1 month before the start of the trial (administration of the substance for clinical trial) Drug metabolizing enzyme induction and inhibition drugs such as barbiturates Drug taking medication that will affect the clinical trial within 10 days before starting the test One person

12. Anyone who has had an unusual meal that may affect the absorption, distribution, metabolism and excretion of the drug.

13. Those who can not take low calcium diet when participating in clinical trials

14. Those who have donated whole blood within 60 days before the initiation of the trial (administration of the substance for clinical trial) or those who donated blood within 20 days before the start of the trial

15. Persons who continue to consume caffeine (coffee> 5 cups / day) or who can not consume caffeine-containing foods during the period from 24 hours before discharge to hospital discharge

16. Persons who are continuously drinking (alcohol> 30 g / day) or who can not abstain from 24 hours before discharge to discharge

17. Excessive smoking (cigarette> 10 cfu / day) or who can not quit during the period from 24 hours before discharge to discharge

18. Pregnant women or persons who are unable to maintain adequate contraception during the course of the trial

19. Experiments Those who are found to be inadequate to participate in clinical trials due to the test results or other reasons

<2-2> Capacity and Duration Check

The purpose of this clinical trial is to evaluate the calcium absorption and the change of iPTH, as well as the safety evaluation of the human body in the present invention, and to ascertain whether calcium absorption effect is actually present in the mineral water. To do this, it is necessary to check the volume and duration of the mineral water before clinical experiment.

The inventors of the present invention have selected calcium carbonate which is higher in absorption rate after fasting than in fasting state. In general, in order to evaluate the change of calcium absorption, elemental calcium should be taken more than 300 mg per day. Calcium carbonate contains 400 mg of elemental calcium per gram .

Calculating the capacity of the mineral water of the present invention containing calcium of similar capacity, the maximum capacity of the mineral water to be used in this clinical experiment was set to 240 mL and the period of administration of the mineral water was limited to one week.

<2-3> How to give subject number

Screening numbers in the form of SXX (ie, in order of written consent, S01, S02, etc.) shall be given to the volunteers who have agreed in writing to participate in the clinical trial, A random assignment number of RXX (eg given as R01, R02, etc.) was assigned on the first day of admission (-1d) for clinical trial substances and medicines using the open software R. One subject was assigned a random assignment number and used as the subject identification code to identify the subject until the end of the clinical trial.

<2-4> Method of administration and eating / drinking

For the clinical trial of the present invention, all subjects were provided with a low calcium diet during the hospital stay and all subjects were admitted to the Clinical Trial Center Research Ward at around 3 pm -1d 1 day prior to the first administration (1d) And served dinner (low calcium diet) around 7 pm. After that, we fasted except for drinking water.

After breakfast at around 8:00 am on the first administration day and at 8:30 am in the morning after the first administration, substances and medicaments corresponding to each group were administered for the first time. After the administration, oral administration of the substances and medicines were carried out. In addition, during the test period after the initial administration, the subjects were kept in a sitting position or standing posture of 45 ° C or higher for at least 4 hours after taking the test substance. Four hours after administration, the first meal was served and all subsequent meals were also served as low calcium diets.

<2-5> Combined medications and precautions

During the clinical trial period, except for substances and medicines for clinical trials, all drugs were not administered. However, if necessary, such as the treatment of harmful cases, it should be administered according to the judgment of the examiner. If the drug is expected to affect the pharmacodynamic and safety evaluation of the trial, the subject is dropped do. All medications and reasons for administration should be listed in the supporting documentation and case record, and signed by the investigator / representative. Other drug administration should be made by the subject in consultation with the researchers.

During the hospitalization period, we did not allow any food other than the meals and water that was provided, and we had to fast (except for drinking water) after dinner (low calcium diet) at around 8 pm the day before the clinical laboratory test, and other lifestyle factors Drinking, smoking, severe exercise, etc.) were limited as much as possible.

<2-6> Pre-clinical screening and selection of subjects

All subjects were screened 4 weeks before the first dose to select clinical subjects, and those who had clinically significant abnormalities were excluded from the following examinations.

1) Demographic information and interviews

(Rounded to the first decimal place, cm), body weight (rounded to two decimal places to one decimal place, kg), and history, blood supply, clinical trials Participation experience, and drug use.

2) Physical examination

The patient may be suffering from a general condition, nutritional status, skin / mucous membrane, eye, non-human thyroid gland, thyroid, lung, heart / circulatory system, abdomen, kidney /

3) Signs of vitality

Blood pressure (sitting position), pulse rate, body temperature (blood pressure and pulse rate were measured while maintaining the sitting position for more than 5 minutes without sudden position change)

4) 12-lead electrocardiogram

The PR interval (msec), QRS (msec), QT / QTc (msec), and analysis of the circulatory organ were recorded in addition to the basic test items.

5) Experimental test: Hematology, blood chemistry, special chemistry, and urinalysis were performed.

Hematology: WBC with differential count, RBC, hemoglobin, hematocrit, MCV, MCH, MCHC, platelets

② Blood chemistry: Glucose, BUN, uric acid, cholesterol, total protein, albumin, total bilirubin, alkaline phosphatase, AST, ALT, γ-GT, LDH, creatinine, Na, K, Cl, Ca

③ Special chemical test: 25 (OH) Vitamin D3

④ Urine test: Specific gravity, pH, protein, glucose, ketone, bilirubin, occult blood, urobilinogen, nitrite, microscopy

⑤ Pregnancy response test: Urine-HCG (It was performed using urine sample for urine test only for female subjects.)

6) Serum test: HBsAg, anti-HCV Ab, anti-HIV Ab

Of the 31 participants who participated in the preliminary test described above, 24 subjects who did not meet the selection criteria and who did not meet the exclusion criteria were divided into three groups of subjects A, B, and C as clinical trial subjects.

Table 3 shows demographic information and vital signs of subjects in each group.

<2-7> Each group Substances for clinical testing  And drug dose

In order to investigate the calcium absorption effect of the present invention in the mineral water of the present invention divided into three groups of A, B and C, the dose of the substance for clinical test and the dose of the drug were set as follows, Lt; / RTI &gt;

Group A: 1, 7d After 30 minutes of breakfast, 240ml of Jinjin hot spring water and 100mL of mineral water were administered. After 2-6d breakfast and 30 minutes after dinner, 120ml of Jinjin hot spring water and 100mL of mineral water were administered.

Group B: 1, 7d After 30 minutes of breakfast, 2 tabs of calcium preparation, 240 mL of physiological saline, and 100 mL of water were administered. After 1 hour of 2-6d breakfast and 30 minutes after dinner, 1tab of calcium formulation, 120 mL of physiological saline solution and 100 mL of living water were administered.

Group C: 1, 7d After 30 minutes of breakfast, 2 tabs of calcium preparation and 340 mL of water were administered. After 1 hour at 2-6d and 30 minutes after dinner, 1tab of calcium preparation and 220mL of water were administered.

Where d is the abbreviation for day and represents the progression during the clinical trial.

< Example  3>

Assessment of calcium absorption

<3-1> Parathyroid hormone iPTH )

The concentration of parathyroid hormone was measured in the subjects to see if the calcium absorption effect of the inventive mineral water was actually present.

First, in order to indirectly evaluate the absorption of calcium in the body, 9 blood samples were taken at the 1st, 7th day of the clinical experiment and 0.5, 1, 1.5, 2, 3, 4, The results of the measurement of the hormone (iPTH) showed that the blood levels of parathyroid hormone fell to the highest level in 2 hours after the administration of the test substance and medicines in both groups on the 1st and 7th day of the clinical experiment, but returned to the basal level at 6 hours or 8 hours (See Tables 4 to 5).

The mean value of parathyroid hormone basal values (1d) before administration of drugs and drugs for clinical use were 27.88 in group A, 20.46 in group B and 31.45 in group C, but the baseline value on day 7 of the clinical study was 20.83 in group A and 19.26 in group B , And group C (24.34) showed a tendency to decrease the basal parathyroid hormone level after administration of drugs and medicines for 1 week (see FIG. 2).

In general, when the calcium intake is insufficient or the calcium concentration in the blood is insufficient due to other causes, parathyroid hormone is secreted from the parathyroid gland. In the group of the mineral water ingestion of the present invention, the parathyroid gland hormone level is decreased by the calcium- Could know.

<3-2> Ionized Calcium

To determine whether the mineral water of the present invention actually has a calcium absorption effect, the concentration of ionized calcium in the testee was measured.

First, in order to indirectly evaluate the absorption of calcium in the body after administration of the mineral water and medicines (calcium preparation) of the present invention, 6, and 8 hours, and the degree of ionized calcium was measured. As a result, it was found that the ionized calcium concentration tended to increase at the end of the clinical experiment rather than at the start of the clinical experiment (see FIG. 3) .

<Example 4>

Bone loss  Guided animal modeling

A bone loss induction mouse model was prepared to examine whether the mineral water of the present invention according to Example 1 had a calcium supplementation effect.

5 to 6 weeks old healthy male C57BL / 6 was cultivated for 2 weeks or longer in an environment free from pathogens. The mineral water of the present invention was diluted with 30% of the water, and the mineral water powder mixture was used as a feed. This was done under the approval of the IACUC (Institutional Animal Care and Use Committee). As shown in Table 1, twelve animal experimental groups were made and the following experiments were carried out.

The animal model group of the present invention Calcium deficiency diet control + general drinking water RL + general drinking water RL + Bisphosphonate (B.P) + common drinking water RL + B.P + 30% marine mineral water RL + 30% marine mineral water RL + 30% marine mineral water powder mix feed + general drinking water A normal diet control + general drinking water RL + general drinking water RL + Bisphosphonate (B.P) + common drinking water RL + B.P + 30% marine mineral water RL + 30% marine mineral water RL + 30% marine mineral water powder mix feed + general drinking water

The mineral water powder mix feed was prepared by crushing the calcium deficient diet feed / general dietary feed, and 900 mg of 30% of 3 g of the daily intake of 5-week-old mouse was mixed and re-kneaded with a certain amount of sterilized water and dried in an oven , And the RL in Table 1 represents the nuclear factor-kappaB ligand (RANKL).

Twelve animal groups were inoculated with marine mineral water and powder for 1 week. Bisphosphonate (BP) was injected subcutaneously into the positive control group at 10 ug / kg. In all groups except the negative control group, To induce bone damage.

&Lt; Example 5 >

Calcium supplementation effect of mineral water according to the present invention

<5-1> x-ray and CT measurement

Two days after the injection of sRL into the animal test group prepared in Example 4, xRL-induced bone loss was induced by sRL. Calcium supplementation effect was confirmed.

As a result, it was confirmed that the bone loss due to sRL was definitely induced as compared with the control (see Fig. 5) as seen from G2. G3, a group injected with bisphosphonate (BP), was found to retain the shape of a trabecular bone as the osteoclast activity was inhibited. G4, a group of bisphosphonate (BP) and mineral water, The shape of the trabecular bone was maintained. However, G2 and G3 show a slight difference. In G3, the trabecular bone appears to be whitish, whereas the G4 sponge trabecular bone is located on the right side of the photograph. ) Showed normal bone morphology.

In G5, which consumed only marine mineral water after inducing bone loss, the amount was slightly similar to that of G1, which is a normal group in which bone loss was not induced, but it was similar to that of G6, which was fed with mineral water powder (See FIG. 6).

<5-2> Measurement of bone volume and thickness

In order to examine the volume and thickness of bone in the animal experimental group prepared in Example 4, the samples of each animal group were analyzed by uCT. As a result, in the mouse model in which bone loss was induced, (Fig. 7 to Fig. 8). Fig. 7 is a graph showing changes in bone volume and thickness of a normal mouse group.

The present invention has been described with reference to the preferred embodiments. It will be understood by those skilled in the art that various changes in form and details may be made therein without departing from the spirit and scope of the invention as defined by the appended claims. Therefore, the disclosed embodiments should be considered in an illustrative rather than a restrictive sense. The scope of the present invention is defined by the appended claims rather than by the foregoing description, and all differences within the scope of equivalents thereof should be construed as being included in the present invention.

Claims (7)

Gangwon-do, Gangneung-si, Gyeonggi-do, South Korea 92-1, Jinjeong-ri, Kangwon-do, Korea The method according to claim 1,
The mineral water contains, as minerals, at least one selected from the group consisting of potassium 200-230 mg / L, sodium 7000-9500 mg / L, calcium 1400-1700 mg / L, magnesium 900-1100 mg / L, zinc 3-9 mg / L of manganese, 1 to 3 mu g / L of cobalt, 600 to 950 mu g / l of titanium, 200 to 500 mu g / L of selenium, 65 to 75 mu g / L, 3 to 9 ㎍ / L of copper, 0.02 to 0.09 mg / L of lithium, 16000 to 19500 mg / L of chlorine ion, 1.5 to 3.0 mg / L of fluorine ion, 40 to 56 mg / 4500 mg / L, boron 0.8-1.2 mg / L, and silicon dioxide 0.5-15 mg / L. The method according to claim 1,
Wherein the mineral water is a concentrate obtained by concentration and desalting treatment, and the concentrate contains 0.5 to 50% (v / v) based on the total weight of the composition. The method according to claim 1,
Wherein the mineral water reduces the level of blood parathyroid hormone (iPTH) and increases the concentration of ionized calcium. A pharmaceutical composition for the prevention and treatment of osteoporosis, which comprises as an active ingredient marine mineral waters taken from a site 1100m below a hot spring area in a coastal area of Gangneung-ri, Gangneung-ri, Gangneung-gun, Gangneung-gun, Republic of Korea. 6. The method of claim 5,
The mineral water contains, as minerals, at least one selected from the group consisting of potassium 200-230 mg / L, sodium 7000-9500 mg / L, calcium 1400-1700 mg / L, magnesium 900-1100 mg / L, zinc 3-9 mg / L of manganese, 1 to 3 mu g / L of cobalt, 600 to 950 mu g / l of titanium, 200 to 500 mu g / L of selenium, 65 to 75 mu g / L, 3 to 9 ㎍ / L of copper, 0.02 to 0.09 mg / L of lithium, 16000 to 19500 mg / L of chlorine ion, 1.5 to 3.0 mg / L of fluorine ion, 40 to 56 mg / 4500 mg / L, boron 0.8-1.2 mg / L, and silicon dioxide 0.5-15 mg / L. 6. The method of claim 5,
The pharmaceutical composition for the prevention and treatment of osteoporosis, wherein the mineral water is a concentrate obtained by concentration and desalting treatment and concentration, and the concentrate contains 0.5 to 50% (v / v) based on the total weight of the composition.

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