JPH0448421B2 - - Google Patents

Description

[Detailed description of the invention]

The present invention relates to a calcium malate/calcium citrate composite composition and a method for producing the same. More specifically, a method for producing a calcium malate/calcium citrate composite composition by reacting a certain ratio of citric acid (or its sodium salt) and malic acid (or its sodium salt) with a certain calcium salt. Regarding. Although the food situation in our country is improving year by year with economic development and the general nutritional status is also improving, only calcium is lacking in nutritional balance.
Recent results of the National Nutrition Survey conducted by the Ministry of Health and Welfare show that the average intake of calcium is insufficient, and vitamin _B1 is also insufficient. In view of these circumstances, the inventor has conducted numerous studies with the aim of researching and developing a calcium supplementary food that also serves as nutrition as a countermeasure to this problem, and has finally determined that the calcium form of organic acids in the Kreb's citric acid cycle series has ideal conditions. Of course, there are many other substances that can be used as sources of calcium supplementation, but organic acids of the Kreb's citric acid cycle system should be considered as the only substances that are directly involved in heat calorie metabolism at the same time as calcium supplementation. Citric acid, in particular, is absorbed immediately after ingestion, immediately enters the Kreb's citric acid cycle, and is involved in heat energy metabolism. The fact that the average per person in the results of the Ministry of Health and Welfare's national nutrition survey is around 300 mg per day, which is below the nutritional standard requirement for calcium set out in the Ministry of Health and Welfare White Paper, is 600 mg per day for each adult, which is a major problem in terms of national health. Calcium 600 per day per adult according to the Ministry of Health and Welfare White Paper
mg intake should be considered to be very reasonable, and these are values determined by determining the daily required amount based on one nutritional basis, and considering the amount excreted by the body's calcium metabolism, that is, the amount in feces. Endogenous calcium loss of
100mg, the amount excreted in urine is around 130mg, the amount excreted in sweat is 30
mg, a total of 260 mg will be excreted. If we assume that the calcium digestion and absorption rate in food is 50%, we can calculate that it is sufficient to take in 520mg of calcium, and based on these results, we can see that the required amount of 600mg/day is reasonable considering the amount of excretion (in the past, calcium intake was (1g per adult per day). When we consider the causes of the lack of calcium intake among the Japanese people today, we find that: (1) Japanese people live on an acidic plateau, which is characteristic of volcanic countries, so they have less calcium than their European and American soils; Therefore, the fundamental and fateful cause is that the amount of calcium in ground crops and other foods is particularly low, and that Japanese people have a diet that relies on general foods with low calcium content. (2) Calcium is one of the most important nutrients, and even if its intake is insufficient or inadequate, like the other three major nutrients, it can cause hunger and starvation due to insufficient intake, fasting, etc. There are no subjective symptoms such as a condition, and therefore it is dangerous. There is currently no method for early detection of calcium deficiency, and there is no known isolated calcium deficiency. Due to these factors, there is a tendency for calcium intake to be neglected. (3) General members of society lack awareness regarding the importance of calcium in physiological functions other than teeth and bones. are excreted unchanged every day, and the calcium requirement for these, which is particularly involved in physiological effects, is compensated for by the dissolution of the bone, which is an autologous calcium store; Fractures cause osteoporosis. As mentioned above, the most ideal way to counter the lack of calcium intake in Japanese people is to supplement calcium through dietary improvements, but this requires an appropriate calcium supplement. The fact that it is extremely difficult for each Japanese person to consume 600 mg of calcium in their current dietary habits according to the Ministry of Health and Welfare's white paper can be idealized by referring to the ``Japanese Food Composition Tables, compiled by the Science and Technology Agency Resources Investigation Committee.'' Not only housewives at home, but also people in charge of preparing menus for group lunches and school lunches, need to create food selection menus that are well-balanced within a certain economic framework, especially in order to satisfy calcium requirements. The economic aspect is most difficult to overcome when relying on calcium-deficient food ingredients. In view of the above-mentioned circumstances, and based on a nutritional standpoint, the ideal system is the Krebs cycle (citric acid cycle or
As mentioned above, we selected calcium citrate, which is a representative organic acid of the TCA cycle) series.Of course, there are many other calcium supplements, but those that are directly involved in metabolism as well as direct calcium supplements. There are only organic acids in the Krebs cycle series, especially citric acid, which immediately enters the Krebs cycle and rotates, so that the final decomposition products of ingested nutrients are combined with oxalo complex acids, which are active complex acids and are present in living tissues. It starts to become citric acid and can enter the Krebs cycle. Therefore, citric acid is a physiological component, has no heterospecificity, is easily absorbed, and is a basic factor of heat energy metabolism that can directly enter the Krebs-citric acid cycle. Also, in Dr. Krebs' biological experiments, ``a small amount of citric acid significantly promotes cellular respiration.'' During the citric acid cycle, citric acid is gradually transferred into the muscles, and its intermediate products are rapidly oxidized by the muscles. Based on these experimental facts, he published the Kreb's citric acid cycle theory in 1937, and was awarded the 1952 Nobel Prize. After the ingested nutrients are digested and broken down,
These are the theories that elucidate the pathway leading to the generation of oxidative decomposition thermal energy at the final stage. As mentioned above, the organic acids of the Krebs-citric acid cycle are absolutely indispensable for heat energy metabolism in living organisms, and it is an undeniable fact that living organisms sustain life through these organic acids. is considered most important. Therefore, it is close to ideal in terms of health promotion that these organic acid binders can supplement calcium and at the same time enhance internal metabolism more smoothly. However, calcium salts of organic acids in the citric acid cycle series, especially calcium citrate, are sparingly soluble in water, and their range of use in food products is extremely narrow, making them particularly inapplicable to beverage products that compete for transparency. There is. The present inventor aims to widely apply calcium citrate as a calcium supplement source in the food sector, and as a result of repeated research on the increase in the water-soluble tendency of calcium citrate, Reached. By allowing calcium malate to coexist with poorly water-soluble calcium citrate, it is more than three times more soluble in water than conventional calcium citrate (PH6-6.5), and 5.9 times more soluble than the entire complex. Therefore, calcium citrate can be widely used in the food sector, and can be easily applied to beverages in a neutral state, especially in terms of transparency. Due to the coexistence of calcium malate molecules with calcium citrate molecules, the physical property change in which the water solubility of calcium citrate molecules increases is due to the coexistence effect of calcium malate molecules on calcium citrate molecules. We experimentally researched and confirmed the fact that physical properties change as the dissolution rate increases in water. Based on this fact, it can be assumed that the relative optimal coexistence ratio of malic acid molecules to calcium citrate molecules is related to the maximum dissolution rate of calcium citrate molecules in water. On the other hand, the quantitative ratio change of calcium malate was systematically and sequentially changed in magnification, and the results of a water solubility comparison test were investigated for each of the various test samples. The coexistence ratio of calcium citrate and calcium malate that showed the highest dissolution rate was 59.14% for calcium citrate and 40.8% for calcium malate. Calcium 60% Calcium malate 40% The reason why calcium malate increases the water solubilization of calcium citrate is unfortunate, but the following may be considered. Changes in physical properties of calcium citrate in water: Comparison of dissolution rate of calcium citrate alone in water and dissolution rate of calcium citrate/calcium malate complex Dissolution rate of calcium citrate Calcium citrate/calcium malate complex 18℃ 0.0849 g in 100 ml of water 0.5 g in 100 ml of water at 20°C The dissolution ratio of calcium citrate in the calcium citrate/calcium malate complex is the dissolution rate of the complex: 0.5 g x 0.59 = 0.259 g ... Amount of calcium citrate dissolved in the complex Then,
Calcium citrate in the coexisting body is 3.47 times more soluble than calcium citrate alone (0.295÷0.085=
3.47 times). Regarding the mechanism of calcium malate relative to calcium citrate, it was experimentally confirmed by a basic water solubility test that a 40.8% coexistence ratio of calcium malate to calcium citrate showed the maximum water solubility. Regarding this fact, the numerical values calculated from the relative molecular weights of both calcium citrate and calcium malate as a presumed molecular bond also match in terms of their relative chemical structural formulas. Amount of each calcium in calcium citrate and calcium malate Calcium citrate molecular weight (anhydrous) = 498.4 Calcium 120 = 3 atoms Calcium malate molecular weight = 172. Calcium medium
40 = 1 atom Therefore, the amount of calcium citrate salt and calcium malate salt per 1 g of calcium in each salt is calcium citrate = 498 ÷ 120 = 4.154 Calcium malate = 172 ÷ 40 = 4.300. Based on the basic water solubility test results, calcium citrate
Since the coexistence ratio of 60% calcium malate and 40% showed the maximum water solubility phenomenon of calcium citrate, calcium citrate 4.154 x 0.6 = 2.4924 calcium malate 4.3 x 0.4 = 1.72. Therefore, by comparing these numerical values with their respective molecular weights and looking at their quantitative relationship, it is possible to know the state of the mutual intermolecular relationship between the two. Calcium citrate is 60% = 2.492 x 100 ÷ 498.4 = 1/2 molecule Calcium malate is 40% = 1.72 x 100 ÷ 172 = 1 molecule If 1/2:1 = is the mutual molecular structure and real value, It should be considered as 2 molecules of calcium malate and 1 molecule of calcium citrate. Separately, as already stated, the relative proportions of calcium citrate and calcium malate to each calcium amount are 60% calcium citrate and 40% calcium malate, which means that if converted to the number of pure calcium atoms, citric acid Calcium has 3 atoms, and calcium malate has 2 atoms. Therefore, if we look at the number of calcium atoms bound in each molecule of calcium citrate and calcium malate, we can see that: Calcium citrate → 3 atoms of calcium in the molecule Calcium malate → 1 atom of calcium in the molecule Calcium malate This means that two molecules of calcium malate coexist due to the arrangement of two atoms.
Therefore, it can be seen that one molecule of calcium citrate and two molecules of calcium malate coexist. The fact that calcium citrate, which is poorly water-soluble, increases its solubility in water at these mutual ratios can be presumed to be due to changes in physical properties of calcium citrate that occur in the coexistence of calcium malate. Due to the already described distribution number of calcium atoms for each acid, the coexistence of 2 molecules of calcium citrate and 1 molecule of calcium malate caused the change in the physical properties of calcium citrate with respect to water. This is thought to be due to some kind of intermolecular bond with calcium malate. Then,
The composite composition of the present invention is not simply a mixture of calcium organic acids. Since it is clear that one molecule of calcium citrate and two molecules of calcium malate coexist, if we discuss and examine the relationship between them from the perspective of each molecular structure, we can find the bonding state between the molecules as follows. It can be estimated.
Calcium citrate consists of two molecules of citric acid and three atoms of calcium, and calcium malate consists of two molecules of malic acid and two atoms of calcium. The probable cause of molecular hydrogen bonding is due to the relationship between one molecule of calcium citrate and two molecules of calcium malate in terms of their respective molecular structures. As shown above, it can be assumed that two molecules of calcium malate exist in an additional molecular hydrogen bond with one molecule of calcium citrate. Based on these molecular structural formulas, the relative ratio of each calcium salt of malic acid citrate is 172 x 2 x 100/172 x 2 + 498 = 4.85% Calcium malate coexistence ratio 498 x 100/172 x 2 + 498 = 59.14% Calcium citrate Coexistence ratio (calcium malate molecular weight 172, calcium citrate molecular weight 498 (as anhydrous)) The relative ratio of calcium in each calcium salt is calcium citrate = 3 atoms, calcium malate 1 atom x 2 = 2 atoms ∴ 3:2 This is exactly the same as the calculated value of the basic dissolution test experimental result. These are estimated molecular formulas and inferences based on experimental results, and the basis for these confirmations will be confirmed through future physical and chemical tests. However, as a practical matter, poorly water-soluble calcium citrate (18°C water 100%
0.085g dissolved in ml), a complex of 60% calcium citrate and 40% calcium malate in 100ml of water at 20°C.
The actual phenomenon of dissolving 0.5g is more than three times the dissolution rate of calcium citrate alone, which is 0.085g/100ml (calcium citrate in the complex is 60% = 0.3g). The increased water solubilization tendency due to changes in the physical properties of calcium citrate has wide application value in various fields, and it can be used as a nutritional calcium salt to strengthen foods, especially beverages, that compete for transparency in a neutral state, as well as all other foods. As nutritional calcium, it does not change the original flavor of the food, and its fortification application when cooking rice has been tested, and the Japanese people, who have a strong sense of discrimination when it comes to cooked rice, ingest it without any objections. It could also be added.
Content composition and physical properties of complex with calcium citrate and calcium malate 1 Physical properties 20% for white crystalline fine powder tasteless and odorless water
℃Dissolve 0.5g in 100ml (dissolved in neutral pH 6)
~6.5) Theoretical content composition Calcium citrate 54.42% Calcium malate 37.60% Pure calcium (Ca) 21.7% Moisture 8% Japan Food Research Center No. 11120588 Analysis test results 1978-12-23 Citric acid 42.1% Apple Acid: 26.7% Calcium: 19.5% Water: 11.4% The analysis results of citric acid and malic acid by gas chromatography are also in good agreement with the theoretical content composition. Experimental example Regarding the results of thermogravimetric analysis (TG) and differential thermal analysis (DTA) of calcium citrate, calcium malate, and ACAL, Equipment used: Seiko Electronics thermal analyzer G-5000 Measurement conditions: Heating rate: 5deg/min ., Temperature increase limit: 300deg., Test drying temperature: 35deg., Sample container: Al Sample 1 Calcium citrate (special grade reagent) 2 Calcium malate (add calcium chloride to sodium malate solution and collect the resulting precipitate by filtration) and then washed with warm water until no chlorine ions are detected, and then air-dried at room temperature.) 3. ACAL (trade name, product of the present invention) 4. ACAL (MIX-1) (manufactured according to the manufacturing method of the present invention, provided that (It was air-dried without drying at 110-120℃) 5 ACAL (MIX-2) (same bulk as MIX-1, but different samples were used because filtration and washing were different) 6 Calcium citrate malate-1 (Sample 1. Calcium citrate and Sample 2. Calcium malate were weighed out at a molar ratio of 1:2 and mixed well using an agate mortar.) 7 Calcium citrate malate-2 (Sample 1. Calcium citrate and sample 2. Weigh out calcium malate at a molar ratio of 1:2, mix well using an agate mortar, add water to form a slurry, stir further, and air dry) Results and discussion Calcium citrate (Cit ₂ -Ca The crystallization water of ₃ −4H ₂ O) loses two molecules by 107℃, and loses two more molecules by 154℃.
It loses molecular water and becomes anhydrous. In calcium malate (Mal−Ca−3H ₂ O)
By the time it reaches 116℃, it loses two molecules of water and becomes a monohydrate salt.
Molecular water is lost up to 257°C. ACAL (product) has been dried once, so the amount of water released by heating is not quantitative, but it is heated at 230℃, which is lower than the temperature of one molecule of water in calcium malate.
It's completely dry by now. This elimination process is quite different from that of calcium citrate and calcium malate. Eical (MIX-1) is air-dried and is expected to have a composition of calcium citrate ( _{Cit2 -Ca3-4H2O} ) and calcium malate (Mal-Ca _{- 3H2O} ). Seven molecules of water contained in the crystal are continuously eliminated and become anhydrous at 211℃. This desorption process was similar to that of Eikal (product). Eikal (MIX-2) and Eikal (MIX-1)
gave similar results. Calcium citrate malate-1 may have been slightly dehydrated during handling and cannot be considered. Calcium citrate malate-2 is dehydrated by citric acid at 116°C, the desorption temperature of two water molecules from malic acid. The number of molecules of water, two molecules of water due to malic acid, is somewhat large, but by the time the next two molecules of water from citric acid are released, at 168°C, only 6 molecules of water are released in total, and the number of water molecules from malic acid is It can be seen that the water in the last molecule does not desorb until the temperature reaches 250°C. In other words, the process of desorption of crystal water from calcium citrate-malate-2 is that of calcium citrate (Cit ₂ -Ca ₃ -4H ₂ O) and calcium malate (Mal-Ca-3H ₂ O) independently. They can be thought of as overlapping. Therefore, it can be said that the structure of water of crystallization in Eical crystals is different from the structure of water of crystallization in crystals of calcium citrate, calcium malate, and mixtures thereof. Conclusion ACAL cannot be said to be a simple mixture of calcium citrate and calcium malate. No conclusion can be drawn from the above results regarding the state of Eical dissolved in water. Eical is likely to be a mixed crystal due to coprecipitation. If it is a mixed crystal, it is thought that it will behave in the same way as a mixture in an aqueous solution.

[Table] Example 1 Citric acid, malic acid, and Ca carbonate are all pharmacopeia products or food additive regulations Citric acid (with 1 molecule of crystal water) 2 molecular weight Malic acid 2 molecular weight is added to 1800 ml to 2000 ml of water in advance dissolve. After complete melting, heat from the outside until the internal temperature reaches 50° to 60°C.
Add 500 g of calcium carbonate to this, being careful not to bubble the contents, and stir the contents thoroughly. After a while, it becomes a white crystalline slurry that almost fills the container. After standing for three hours, the mother liquor was separated and dried in a dryer using an appropriate method, and finally dried at 110° to 120°C for 1 to 2 hours.
Drying, which also serves as time sterilization, is performed and the final product is made after cooling. Example 2 Method of exchange separation with calcium chloride from sodium citrate and sodium malate salt solution 588 g of calcium citrate and 356 g of sodium malate were dissolved in 1500 ml to 2000 ml of 50°C warm water, and chlorinated in a separate container in advance. 740g of calcium
Gradually add something that can be dissolved in 1000 ml of warm water (50°C) and keep stirring the contents, and some of the white crystals will precipitate out. After all of the calcium chloride solution has been added, the contents are sufficiently stirred and then left at room temperature for 2 to 3 hours, with occasional stirring during this period. When left to stand for an additional 1 to 2 hours, the white crystals settle and separate into a clear upper layer. Separate the upper layer liquid and crystals by an appropriate method (more than 460 g of NaCl is dissolved in the mother liquid). Separated crystals are 1~
After washing twice with the same volume of warm water, dehydrate and dry. Finally, drying, which also serves as sterilization, is continued at a temperature of 110 to 120°. After cooling, this is used as a product. Next, the molecular formula for chemical exchange separation is as follows. The amount of each raw material used can be calculated from the molecular equivalent of each chemical, and metaplastic crystals are calcium citrate and calcium malate 59.14
%: Shall have a content composition of 40.85%. Calcium citrate 2C ₆ H ₅ Na ₃ O ₇・2H ₂ O + 3CaCl ₂ = Calcium citrate C ₁₂ H ₁₀ Ca ₃ O ₁₄ Molecular weight 498
Only metaplasia + 6NaCl Calcium malate 2C ₄ H ₄ Na ₂ O ₅・1/2H ₂ O + Calcium chloride 2CaCl = Calcium malate 2C ₄ H ₄ CaO ₅ + 2NaCl Metaplastic calcium with molecular weight 172 x 2 = 344 The relative ratio of salt is 498 + 344 = 842...Amount of metaplastic calcium citrate and calcium malate Calcium citrate 498/842 = 59.14% Calcium malate Calcium 344/842 = 40.85
%, and these are a predetermined ratio of calcium citrate:calcium malate 3:2. Water solubility test 1 to 2 g of the sample of the present invention was ground into a fine powder in a small mortar, and 100 c.c. of water at a temperature of 20°C was added directly to the mortar, and the contents were thoroughly crushed using a pestle. Mix and stir this content for 30 minutes.
When transferred to a 100 c.c. graduated cylinder and left to stand for 3 hours, an excessive amount of insoluble precipitate settles at the bottom and separates into a colorless and transparent upper layer liquid. Accurately collect this transparent upper layer liquid with a 20 ml home pipette, carefully transfer it to a small evaporating dish of known weight, evaporate it on a heavy boiling water pot, and after the content water has evaporated, the remaining solids in the evaporating dish are 1 in a constant temperature dryer at 100~110° with the evaporating dish.
After drying for ~2 hours, leave to cool in an excircator, weigh, and subtract the amount of the evaporating dish whose weight is known from the total weight to obtain the total amount of the sample dissolved in 20 ml. Multiply that number by 5 to get the amount of sample dissolved in 100ml. Small evaporating dish 18.41g 20c.c.m Total weight after evaporation 18.57g 18.57 ∴ −18.41 0.16 0.13×5=0.65g…100c.c. in water 0.16×5=0.8g The product of the present invention is included in the Japanese Pharmacopoeia. The results of a solubility test conducted in accordance with the above are as follows (Shizuoka Prefectural Institute of Health Test Results). 0.4% dissolves. 0.5% Not completely dissolved. 0.6% Same as above Solubility 0.14% (19℃).

Claims (1)

[Claims] 1. A water-soluble composite composition of calcium malate and calcium citrate, characterized in that the molecular weight ratio of calcium malate to calcium citrate is at least 2:1. . 2 Dissolve less than 70% citric acid and more than 30% malic acid in water and neutralize the solution by adding calcium hydroxide or calcium carbonate, or dissolve less than 70% sodium citrate and 30% The above sodium malate is dissolved in water, a corresponding chemical molecular equivalent of calcium chloride is added, and the resulting crystalline precipitate is then separated, each having a molecular weight ratio of at least 2: A method for producing a composite composition of calcium malate and calcium citrate in which calcium malate and calcium citrate are combined at a ratio of 1.