JP6069015B2 - Method for producing organic iodine-containing composition - Google Patents

Description

  The present invention relates to a method for producing an organic iodine-containing composition used as a raw material for organic iodine preparations useful as health foods and pharmaceuticals.

  Organic iodine is safe and has no side effects on the human body, unlike inorganic iodine, which is considered a powerful drug, as evidenced by the results of various safety tests including toxicity tests by the Japan Food Research Center. It is known that it is a powerful anti-reactive oxygen agent that can be administered orally, and is useful for preventing radiation damage, strengthening immunity, treating many intractable diseases and the like. By the way, as a result of research by Dr. Tamzo Makino and Dr. Noboru Iijima in the past from around 1920 to 1935, iodine preparations made from cod liver oil, Borneolum, creosote and iodine (common name: Makinoiodo or Neo Extract) In addition to hypertension, vascular sclerosis, tuberculosis, asthma, gastric ulcer, leukemia, etc., it has been reported to have a wide variety of medicinal effects such as cancer and AIDS. In addition, there is a report that the effect of inhibiting the growth of cancer (breast cancer) by iodine (iodine) is also expected (Non-patent Document 1). Furthermore, it has been reported that organic iodine has an effect of activating metabolic functions, adjusting hormone balance, recovering from fatigue, and purifying and strengthening blood vessels (Non-patent Document 2).

  Such organic iodine is generally produced by a method in which iodine is heat-added to the liver oil of cartilage fish such as cod, shark, ray or the like or the fat component extracted from the liver oil. In the conventional production method, reagent-grade granular iodine is added while the liver oil or fat component is heated to about 115 to 160 ° C. so that iodine (melting point 113.7 ° C.) dissolves and reacts. In addition, a heat addition reaction is performed in which iodine is added to the double bond in the oil and fat molecule.

Journal of Japanese Cancer Therapy, March 1994 Biomedical Science Information Center “About Organic Iodine”, Supervised by: Professor Emeritus, St. Marianna University School of Medicine, Noboru Iijima, Online search date October 18, 2012, Internet http://seimei-ikagaku.info/pdf/yodo_nituite .pdf

  However, in the conventional method for producing organic iodine, a sudden exotherm is often generated during the addition reaction, and the reaction cannot be controlled (so-called runaway reaction). In addition to the risk of dissipating outside, the product has a significant increase in viscosity, and black resinous sludge due to the polymer is often produced as a by-product. The extremely high-viscosity product causes a fatal problem that it cannot be injected into a capsule when it is soft-encapsulated as an organic iodine preparation. The resinous sludge produced as a by-product is a polymer that is difficult to digest in the body, but fine particles remain even through the filter, and easily adhere to the wall and bottom of the reaction vessel. Since it is insoluble or hardly soluble, it takes a lot of labor and time to peel and wash, and there is a problem that it becomes difficult to extract the product when it is fixed to the bottom plug valve of the reaction vessel.

  As described above, harmful iodine gas is generated because the iodine value of liver oil of cartilaginous fish is as high as 150 or more, there are many double bonds of oil and fat molecules, and the addition reaction of iodine is an exothermic reaction, When granular iodine that has settled at the bottom of the reaction vessel and does not melt at high density elutes all at once, a sudden exotherm occurs depending on the conditions, and the heat and light cause the oxidation reaction and polymerization reaction to run away with further exotherm. In addition, the temperature in the system rises to a boiling point of iodine of 184 ° C. or more at a stretch, and the intense boiling of iodine is caused. Therefore, in order to suppress a sudden exotherm, a method of adding iodine while adding it little by little and uniformly dispersing it is usually employed. However, the increase in viscosity due to the oxidation reaction or polymerization reaction described above is still caused. Formation is unavoidable and entangles the granular iodine on which the polymer precipitates, resulting in a resinous sludge.

  In view of the above circumstances, this invention, as a method for producing an organic iodine-containing composition, gently and efficiently proceeds the addition reaction of iodine to liver oil, suppress the oxidation reaction and polymerization reaction associated with rapid exotherm, Accordingly, it is an object of the present invention to provide a means capable of preventing the thickening of the product and significantly reducing the by-product of the resinous sludge.

In order to achieve the above object, the method for producing an organic iodine-containing composition according to the invention of claim 1 is characterized in that a liquid obtained by mixing 1 to 10 parts by mass of glycerin with 100 parts by mass of liver oil of cartilaginous fish is 50 to 90 ° C. The mixture is heated, and granular or flaky solid iodine is added to this liquid at a ratio of 1 to 15 parts by mass with respect to 100 parts by mass of liver oil, and an addition reaction is performed.

A second aspect of the present invention, in the manufacturing method of the first aspect of the organic iodine-containing composition, the liquid, which is configured to be added in portions solid iodine in a plurality of times.

Invention of Claim 3 adds the 1-15 mass parts of Borneolum to the product after the said addition reaction in the manufacturing method of the organic iodine containing composition of the said Claim 1 or 2 , and is Borneolum at 100-130 degreeC. It is set as the structure which dissolves.

According to the method for producing an organic iodine-containing composition according to the invention of claim 1, a liquid in which a specific ratio of glycerin is mixed with the liver oil of cartilaginous fish is added in a specific temperature range lower than the melting point of iodine (113.7 ° C.). As the temperature state, granular or flaky solid iodine is added to cause addition reaction . Therefore, this addition reaction becomes a solid-liquid reaction, and since solid iodine is granular or flaky, it does not elute all at once, causing a sudden exotherm, and the reaction proceeds slowly and is solid to liver oil. Since the amount of iodine added is in an appropriate range, the oxidation reaction or polymerization reaction due to heat can be suppressed, and there is no concern that it will become uncontrollable, so that iodine boils and does not generate toxic iodine gas. In addition, since the oxidation reaction and the polymerization reaction are suppressed, the reaction product has a very low viscosity, and the by- product of the resinous sludge is also reduced. Thus, since glycerin is mixed with liver oil in advance, the dispersibility of solid iodine during the addition reaction is improved, and organic iodine, which is an adduct of liver oil / iodine generated on the surface of solid iodine particles, elutes into glycerin. Thus, the particle surface of the solid iodine is constantly renewed, and the reaction efficiency is remarkably increased.

According to the invention of claim 2 , since solid iodine is added in a plurality of times, rapid heat generation during the addition reaction can be more reliably suppressed.

According to the invention of claim 3, since a specific amount of Borneolum is added to the product after the addition reaction and is thermally dissolved in a specific temperature range, unreacted iodine remaining after the addition reaction is not added to the oil. At the same time, the odor peculiar to liver oil is masked and disappeared by Borneolum, and the anti-inflammatory effect by Borneolum is added to the medicinal effect as an organic iodine preparation.

  In the method for producing an organic iodine-containing composition of the present invention, cartilaginous fish liver oil is heated to a temperature of 30 ° C. or higher and lower than 113.7 ° C., and solid iodine is added to the liver oil with stirring to perform an addition reaction. To produce organic iodine which is an adduct of fats and oils / iodine.

  In this case, since the melting point of iodine is 113.7 ° C., the above addition reaction performed by adding solid iodine to liver oil having a temperature lower than the melting point is a solid-liquid reaction between liquid liver oil and solid iodine. In other words, in this solid-liquid reaction, an addition reaction occurs at the interface between the solid iodine particle surface and the liquid liver oil. Thus, as in the conventional case, when the liver oil is heated above the melting point of iodine, the addition reaction is carried out. Does not elute all at once and does not cause a sudden exotherm, and the oxidation reaction and polymerization reaction due to heat can be suppressed. Therefore, in this production method, there is no concern that the reaction will run out of control due to the runaway as in the prior art, and it will not lead to a situation where iodine boils and generates toxic iodine gas. While it becomes difficult to increase the viscosity of the (organic iodine-containing composition), by-product of resinous sludge is also reduced. On the other hand, even if the addition reaction itself is mild with little exotherm, the solid-liquid interface is constantly updated by the liver oil flowing in contact with the entire solid iodine particle surface under stirring, so that the reaction efficiency is high. can get.

  The heating temperature of the liver oil in the addition reaction is in the range of 30 ° C. or more and less than 113.7 ° C. as described above, but preferably by 100 ° C. or less, the by-product of resinous sludge is drastically reduced, In particular, in the range of 50 to 90 ° C., high reactivity is ensured and a sufficiently low viscosity and high quality product is obtained for an organic iodine preparation. In addition, at the liver oil temperature lower than 50 ° C., the rate of the addition reaction is slow and a small amount of unreacted iodine remains, but the reaction system is heated to about 100 to 130 ° C. and maintained for a certain time (about 1 hour). By aging, unreacted iodine is also added to liver oil and is no longer present.

  Examples of the liver oil of the above cartilaginous fish include cod liver oil, shark liver oil, ray liver oil, and the like. For example, an extract from liver oil such as squalene (terpenoid oil) extracted from shark liver oil is also included. The use of cartilaginous fish liver oil in this invention is generally suitable for the production of organic iodine by the addition reaction of iodine because it has a high iodine value of 150 or more and is liquid at room temperature and does not solidify. by.

  Although it does not restrict | limit especially as a solid iodine, The thing of high purity like a reagent special grade is desirable when using it for an organic iodine formulation, and a granular form or flake form is suitable in order to advance an addition reaction moderately.

  The amount of the solid iodine added is in the range of 1 to 15 parts by mass with respect to 100 parts by mass of liver oil. If the amount is less than 1 part by mass, the organic iodine content in the reaction product becomes too low. When the amount is larger, the reaction product thickens due to heat generation and resinous sludge is by-produced. In order to reliably suppress excessive heat generation during the addition reaction, it is recommended that the solid iodine be added in a plurality of times, preferably 5 times or more.

  In order to increase the efficiency of the addition reaction, it is recommended to add glycerin to liver oil in advance. Since this glycerin easily dissolves organic iodine, that is, adducts of liver oil / iodine, by performing an addition reaction in the presence of the organic iodine, the organic iodine produced on the surface of the solid iodine particles elutes into the glycerin, and thus the particles Since the surface is constantly renewed and high reactivity can be maintained, the dispersibility of solid iodine in liver oil is also improved, so that the solid-liquid reaction proceeds promptly. It has also been observed that the addition of glycerin reduces the amount of resinous sludge byproduct. The amount of glycerin added is preferably in the range of 1 to 10 parts by mass with respect to 100 parts by mass of liver oil. Other typical polyhydric alcohols, such as ethylene glycol and propylene glycol, are poorly soluble in adducts of liver oil and iodine, and are not suitable as ingredients for health foods and pharmaceuticals.

  Furthermore, in the method for producing an organic iodine-containing composition of the present invention, Borneolum (powdered with a bicyclic monoterpene also called d-borneol) is added to the product after the addition reaction, and 100 to 130 It is recommended to dissolve Borneolum at ℃. That is, by heating in the above temperature range after the addition reaction, all the unreacted iodine remaining in the reaction product is not added to the liver oil, and the odor peculiar to the liver oil is masked by the dragon brain and disappears. Therefore, there is an advantage that the quality of the organic iodine preparation is improved, and the antibacterial action by Borneolum is added to the medicinal effect of the preparation. The added amount of Borneolum is preferably in the range of 1 to 15 parts by mass with respect to 100 parts by mass of liver oil. However, in the case of squalene as a liver oil extract, since the solubility of Borneolum is as low as about 1% by mass at 25 ° C., much Borneolum cannot be added.

  The organic iodine-containing composition obtained by the above production method contains a large amount of organic iodine, which is an adduct of liver oil and iodine, has a high iodine value, is extremely useful as an anti-active oxygen agent, and has a low viscosity. Therefore, it can be easily injected into soft capsules, so that it can be commercialized as a high-grade iodine preparation for health foods and pharmaceuticals that are soft-encapsulated, and it is easy to incorporate other active ingredients such as wood creosote due to its low viscosity There is also an advantage. Further, as described above, since the by-product of the resinous sludge during the addition reaction is very small, it becomes easy to clean the reaction vessel used for the production.

  Below, the manufacture example of the organic iodine containing composition by this invention is demonstrated concretely including the contrast with the manufacture example (comparative example) on the conditions other than the prescription | regulation of invention. In the following, “%” means “% by weight”. The raw material components used are as follows. The stated viscosity is a value measured with a B-type viscometer.

[Raw ingredient]
Cod liver oil: Cod liver oil from Alaska (iodine value 154.8, saponification value 184.7, acid value 4.0, viscosity at 25 ° C, 37 cp, specific gravity 0.914) Composition: oleic acid 14.8%, linoleic acid 3.4%, linolenic acid 18.8%, EPA 19.2%, DHA 11.3%, other unsaturated fatty acids 14.2%, saturated fatty acids 18.2%
Squalene: Shark liver oil extract (Iodine number 365.8, manufactured by Maruha Nichiro Foods, Ltd.)
Acid value 0.0, specific gravity 0.856)
Granular iodine: Wako Pure Chemical Industries, reagent grade, average particle size of about 2mm
Glycerin: Dietary glycerin manufactured by NOF Co., Ltd. Borneol ...... d-borneol manufactured by Koshiro Pharmaceutical Co., Ltd.

[Production Example 1]
After putting 400 g of cod liver oil into a 1 L round bottom flask and replacing the air in the system with nitrogen gas, it was heated to 200 ° C. with a curved flat blade stirring blade and heated to each temperature described in Table 1 below with an oil bath. Then, 40 g of granular iodine was divided into 10 portions over 4 hours and added in an equal amount (4 g once every 24 minutes) to carry out an addition reaction to produce a dark black liquid organic iodine-containing composition. The results are shown in Table 1 below. The by-product amount of resinous sludge is a product obtained by extracting the product after the reaction and passing it through a 200-mesh cloth, and measuring the residue from the cloth and the sludge adhering to the flask.

  From the results of Table 1, when there is a strong correlation between the temperature of cod liver oil, the viscosity of the product, and the amount of resinous sludge byproduct, the liver oil temperature is higher than the melting point of iodine (113.7 ° C.) (Production No. In .1-6), cod liver oil and iodine adduct, which are dry oils, are thermally polymerized to increase the viscosity significantly, and the amount of resinous sludge by-product increases. In contrast, the lower the liver oil temperature, the lower the viscosity of the product and the less by-product of resinous sludge. Especially at 100 ° C. or less (production No. 1-1 to 1-4), the by-product of resinous sludge. Has fallen sharply. In addition, the products of production Nos. 1-1 to 1-5 whose liver oil temperature is lower than the melting point of iodine have an iodine value close to the calculated value, and iodine is surely added to the double bond of the fat component of liver oil. It can be seen that it is added. However, the production No. 1-6 product with a liver oil temperature of 130 ° C. has a significantly lower iodine value than the calculated value (99.1), and most of the double bonds of the oil and fat components are hot. It is assumed that it is used for polymerization.

  In addition, in the products of production Nos. 1-1 and 1-2 having a liver oil temperature of 50 ° C. or less, a small amount of unreacted iodine was estimated from the iodine value because the rate of the addition reaction was slow. Therefore, water was added to the product to disperse, and after standing for 24 hours, a color test with an aqueous starch solution was performed to qualify free iodine. As a result, slight coloring was observed, and the presence of unreacted iodine was confirmed. It was. On the other hand, as a result of the same color test, it was found that unreacted iodine was not present in the product No. 1-3 produced at a liver oil temperature of 70 ° C.

[Production Example 2]
Glycerin is added to 400 g of cod liver oil in advance in the respective amounts shown in Table 2 below, and in the same manner as in Production Example 1, 40 g of granular iodine is heated at 70 ° C. within 2 hours and 4 hours of reaction time. An organic iodine-containing composition was produced by adding an equal amount dividedly in batches to cause addition reaction. The results are shown in Table 2 below.

  From the results in Table 2, although the addition reaction is relatively difficult to proceed at a liver oil temperature of 70 ° C., the reaction is accelerated by the presence of glycerin in the liver oil, and the addition takes place in a reaction time of 2 hours as estimated from the iodine value. You can see that it is complete. In addition, by-product of resinous sludge is reduced with the blending of glycerin.

[Production Example 3]
In a room equipped with a draft exhaust system, an anchor type stirrer is attached to a reaction tank made of SUS316L with a steam jacket with a capacity of 200L so as to contact the bottom of the reaction tank. Charge 2 kg / cm ² · G steam into the steam jacket under stirring at 150 rpm and heat to the indicated temperature. Divide the indicated amount of granular iodine 10 times within the indicated reaction time. After carrying out addition and carrying out addition reaction, the reaction product was extracted from the bottom plug valve through a 200 mesh filter to obtain a dark black liquid organic iodine-containing composition. The results are shown in Table 3 below.

  From the results in Table 3, by performing the addition reaction at a liver oil temperature lower than the melting point of iodine, particularly preferably 50 to 90 ° C., a product having an iodine value that is extremely low viscosity and close to a calculated value ( Organic iodine-containing composition) has been obtained and resinous sludge by-product is very little. On the other hand, in the production Nos. 3-5 to 3-8 in which the liver oil temperature is higher than the melting point of iodine, the product is highly viscous and has many by-products of resinous sludge. Generation of iodine gas is also observed. In addition, resinous sludge by-produced in production Nos. 3-5 to 3-8 and stuck to the inner surface of the reaction kettle cannot be dissolved by a nonpolar solvent such as xylene, and must be peeled off manually for cleaning. did not become.

[Production Example 4]
Using the same reaction kettle as in Production Example 3, 3 kg of glycerin was added in advance to 100 kg of cod liver oil and heated to 70 ° C., and 10 kg of granular iodine was reacted within 4 hours in the same manner as in Production Example 3. After adding the reaction in 10 equal portions, the mixture was aged at 70 ° C. for 30 minutes, then 10 kg of Borneolum was added to the reaction product and kept at 110 ° C. for 30 minutes with stirring. After aging, the product was extracted from the bottom plug valve in the same manner as in Production Example 3 to obtain 116.4 kg (yield 97.0%) of an iodine-containing composition. The obtained iodine-containing composition had a viscosity (25 ° C.) of 81 cp and an iodine value of 86.5, and as a result of a color test using an aqueous starch solution similar to Production Example 1, unreacted iodine was found. There wasn't. In addition, there was little heat_generation | fever at the time of addition reaction, and the resinous sludge byproduct rate was 0.02%.

[Production Example 5]
Using the same reaction kettle as in Production Example 3, 3 kg of glycerin was added in advance to 100 kg of squalene and heated to 70 ° C., and 10 kg of granular iodine was added within a reaction time of 3 hours in the same manner as in Production Example 3. Addition is carried out in 10 equal portions, and after addition reaction, ripen at 70 ° C. for 30 minutes, then 1 kg of Borneolum is added to the reaction product and ripened by holding at 110 ° C. for 30 minutes with stirring. In the same manner as in Production Example 3, the product was extracted from the bottom plug valve to produce an iodine-containing composition. The obtained iodine-containing composition had a viscosity (25 ° C.) of 46 cp and an iodine value of 290.6, and as a result of a color test using an aqueous starch solution similar to Production Example 1, unreacted iodine was observed. There wasn't. In addition, there was little heat_generation | fever at the time of addition reaction, and the resinous sludge byproduct rate was 0.02%.

Claims (3)

A liquid in which 1 to 10 parts by mass of glycerin is mixed with 100 parts by mass of liver oil of cartilaginous fish is heated to 50 to 90 ° C., and granular or flaky solid iodine is added to 100 parts by mass of liver oil with stirring in this liquid. A method for producing an organic iodine-containing composition, wherein the addition reaction is carried out at a ratio of 1 to 15 parts by mass. The method for producing an organic iodine-containing composition according to claim 1 , wherein solid iodine is added to the liquid in a plurality of times. The manufacturing method of the organic iodine containing composition of Claim 1 or 2 which adds 1-15 mass parts of Borneolum to the product after the said addition reaction, and dissolves Borneolum at 100-130 degreeC.