KR101588441B1 - Method for preparing organic selenium - Google Patents
Method for preparing organic selenium Download PDFInfo
- Publication number
- KR101588441B1 KR101588441B1 KR1020150103788A KR20150103788A KR101588441B1 KR 101588441 B1 KR101588441 B1 KR 101588441B1 KR 1020150103788 A KR1020150103788 A KR 1020150103788A KR 20150103788 A KR20150103788 A KR 20150103788A KR 101588441 B1 KR101588441 B1 KR 101588441B1
- Authority
- KR
- South Korea
- Prior art keywords
- selenium
- solution
- water
- organic selenium
- amino acid
- Prior art date
Links
- 239000011669 selenium Substances 0.000 title claims abstract description 91
- BUGBHKTXTAQXES-UHFFFAOYSA-N Selenium Chemical compound [Se] BUGBHKTXTAQXES-UHFFFAOYSA-N 0.000 title claims abstract description 88
- 229910052711 selenium Inorganic materials 0.000 title claims abstract description 88
- 238000000034 method Methods 0.000 title claims abstract description 9
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 19
- 238000004519 manufacturing process Methods 0.000 claims abstract description 16
- 150000001413 amino acids Chemical class 0.000 claims abstract description 14
- 238000002156 mixing Methods 0.000 claims abstract description 4
- CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 claims description 18
- 235000001014 amino acid Nutrition 0.000 claims description 13
- 235000003704 aspartic acid Nutrition 0.000 claims description 7
- OQFSQFPPLPISGP-UHFFFAOYSA-N beta-carboxyaspartic acid Natural products OC(=O)C(N)C(C(O)=O)C(O)=O OQFSQFPPLPISGP-UHFFFAOYSA-N 0.000 claims description 7
- 239000004210 ether based solvent Substances 0.000 claims description 4
- ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 claims description 4
- 239000004475 Arginine Substances 0.000 claims description 2
- ROHFNLRQFUQHCH-YFKPBYRVSA-N L-leucine Chemical compound CC(C)C[C@H](N)C(O)=O ROHFNLRQFUQHCH-YFKPBYRVSA-N 0.000 claims description 2
- KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 claims description 2
- KZSNJWFQEVHDMF-BYPYZUCNSA-N L-valine Chemical compound CC(C)[C@H](N)C(O)=O KZSNJWFQEVHDMF-BYPYZUCNSA-N 0.000 claims description 2
- ROHFNLRQFUQHCH-UHFFFAOYSA-N Leucine Natural products CC(C)CC(N)C(O)=O ROHFNLRQFUQHCH-UHFFFAOYSA-N 0.000 claims description 2
- 239000004472 Lysine Substances 0.000 claims description 2
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 claims description 2
- KZSNJWFQEVHDMF-UHFFFAOYSA-N Valine Natural products CC(C)C(N)C(O)=O KZSNJWFQEVHDMF-UHFFFAOYSA-N 0.000 claims description 2
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 claims description 2
- 239000004474 valine Substances 0.000 claims description 2
- ODKSFYDXXFIFQN-BYPYZUCNSA-P L-argininium(2+) Chemical compound NC(=[NH2+])NCCC[C@H]([NH3+])C(O)=O ODKSFYDXXFIFQN-BYPYZUCNSA-P 0.000 claims 1
- ZDXPYRJPNDTMRX-VKHMYHEASA-N L-glutamine Chemical compound OC(=O)[C@@H](N)CCC(N)=O ZDXPYRJPNDTMRX-VKHMYHEASA-N 0.000 claims 1
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 abstract description 11
- 238000006243 chemical reaction Methods 0.000 abstract description 10
- 239000000463 material Substances 0.000 abstract description 5
- 239000000126 substance Substances 0.000 abstract description 5
- 231100000419 toxicity Toxicity 0.000 abstract description 5
- 230000001988 toxicity Effects 0.000 abstract description 5
- 239000002904 solvent Substances 0.000 abstract description 2
- 239000003513 alkali Substances 0.000 abstract 1
- 229940091258 selenium supplement Drugs 0.000 description 72
- 239000000243 solution Substances 0.000 description 22
- 210000004027 cell Anatomy 0.000 description 13
- 229940009098 aspartate Drugs 0.000 description 11
- 229940024606 amino acid Drugs 0.000 description 10
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 9
- 238000003756 stirring Methods 0.000 description 7
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 6
- 206010003645 Atopy Diseases 0.000 description 6
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 6
- 238000010521 absorption reaction Methods 0.000 description 5
- 230000000694 effects Effects 0.000 description 5
- 238000002474 experimental method Methods 0.000 description 5
- 238000005507 spraying Methods 0.000 description 5
- 230000002401 inhibitory effect Effects 0.000 description 4
- 239000000047 product Substances 0.000 description 4
- LPXPTNMVRIOKMN-UHFFFAOYSA-M sodium nitrite Chemical compound [Na+].[O-]N=O LPXPTNMVRIOKMN-UHFFFAOYSA-M 0.000 description 4
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 3
- 238000000134 MTT assay Methods 0.000 description 3
- 231100000002 MTT assay Toxicity 0.000 description 3
- 229910021529 ammonia Inorganic materials 0.000 description 3
- 239000007864 aqueous solution Substances 0.000 description 3
- 230000003833 cell viability Effects 0.000 description 3
- 239000012153 distilled water Substances 0.000 description 3
- 239000012091 fetal bovine serum Substances 0.000 description 3
- 235000013305 food Nutrition 0.000 description 3
- 210000002540 macrophage Anatomy 0.000 description 3
- 238000005259 measurement Methods 0.000 description 3
- 238000001953 recrystallisation Methods 0.000 description 3
- 230000004083 survival effect Effects 0.000 description 3
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 2
- LCGLNKUTAGEVQW-UHFFFAOYSA-N Dimethyl ether Chemical compound COC LCGLNKUTAGEVQW-UHFFFAOYSA-N 0.000 description 2
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 2
- 238000002965 ELISA Methods 0.000 description 2
- 206010061218 Inflammation Diseases 0.000 description 2
- MWUXSHHQAYIFBG-UHFFFAOYSA-N Nitric oxide Chemical compound O=[N] MWUXSHHQAYIFBG-UHFFFAOYSA-N 0.000 description 2
- 241000700159 Rattus Species 0.000 description 2
- 238000002835 absorbance Methods 0.000 description 2
- 235000011114 ammonium hydroxide Nutrition 0.000 description 2
- 238000004458 analytical method Methods 0.000 description 2
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 239000008280 blood Substances 0.000 description 2
- 210000004369 blood Anatomy 0.000 description 2
- 238000004113 cell culture Methods 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 239000001963 growth medium Substances 0.000 description 2
- 230000036541 health Effects 0.000 description 2
- 230000004054 inflammatory process Effects 0.000 description 2
- 238000002329 infrared spectrum Methods 0.000 description 2
- 239000003446 ligand Substances 0.000 description 2
- VMGAPWLDMVPYIA-HIDZBRGKSA-N n'-amino-n-iminomethanimidamide Chemical compound N\N=C\N=N VMGAPWLDMVPYIA-HIDZBRGKSA-N 0.000 description 2
- 230000008520 organization Effects 0.000 description 2
- 229910052760 oxygen Inorganic materials 0.000 description 2
- 239000001301 oxygen Substances 0.000 description 2
- 239000002953 phosphate buffered saline Substances 0.000 description 2
- BOLDJAUMGUJJKM-LSDHHAIUSA-N renifolin D Natural products CC(=C)[C@@H]1Cc2c(O)c(O)ccc2[C@H]1CC(=O)c3ccc(O)cc3O BOLDJAUMGUJJKM-LSDHHAIUSA-N 0.000 description 2
- QYHFIVBSNOWOCQ-UHFFFAOYSA-N selenic acid Chemical compound O[Se](O)(=O)=O QYHFIVBSNOWOCQ-UHFFFAOYSA-N 0.000 description 2
- 235000010288 sodium nitrite Nutrition 0.000 description 2
- 229960005322 streptomycin Drugs 0.000 description 2
- 208000024891 symptom Diseases 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- 238000004448 titration Methods 0.000 description 2
- FHYNZKLNCPUNEU-UHFFFAOYSA-N 4-[(3,4-dihydroxyphenyl)methyl]-3-[(4-hydroxyphenyl)methyl]oxolan-2-one Chemical compound C1=CC(O)=CC=C1CC1C(=O)OCC1CC1=CC=C(O)C(O)=C1 FHYNZKLNCPUNEU-UHFFFAOYSA-N 0.000 description 1
- 201000004384 Alopecia Diseases 0.000 description 1
- 206010002383 Angina Pectoris Diseases 0.000 description 1
- 206010003210 Arteriosclerosis Diseases 0.000 description 1
- 241000894006 Bacteria Species 0.000 description 1
- 208000002177 Cataract Diseases 0.000 description 1
- 206010011224 Cough Diseases 0.000 description 1
- 206010012335 Dependence Diseases 0.000 description 1
- 206010012438 Dermatitis atopic Diseases 0.000 description 1
- 208000000059 Dyspnea Diseases 0.000 description 1
- 206010013975 Dyspnoeas Diseases 0.000 description 1
- 206010016654 Fibrosis Diseases 0.000 description 1
- 102000018997 Growth Hormone Human genes 0.000 description 1
- 108010051696 Growth Hormone Proteins 0.000 description 1
- 206010019233 Headaches Diseases 0.000 description 1
- 206010020772 Hypertension Diseases 0.000 description 1
- 238000004566 IR spectroscopy Methods 0.000 description 1
- 206010027476 Metastases Diseases 0.000 description 1
- 102000008934 Muscle Proteins Human genes 0.000 description 1
- 108010074084 Muscle Proteins Proteins 0.000 description 1
- 206010028289 Muscle atrophy Diseases 0.000 description 1
- 206010028813 Nausea Diseases 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- 206010040829 Skin discolouration Diseases 0.000 description 1
- 206010047700 Vomiting Diseases 0.000 description 1
- 208000022440 X-linked sideroblastic anemia 1 Diseases 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 230000003078 antioxidant effect Effects 0.000 description 1
- 208000011775 arteriosclerosis disease Diseases 0.000 description 1
- 206010003246 arthritis Diseases 0.000 description 1
- 201000008937 atopic dermatitis Diseases 0.000 description 1
- 201000011510 cancer Diseases 0.000 description 1
- 239000006143 cell culture medium Substances 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 230000007882 cirrhosis Effects 0.000 description 1
- 208000019425 cirrhosis of liver Diseases 0.000 description 1
- 239000000470 constituent Substances 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 230000037213 diet Effects 0.000 description 1
- 235000005911 diet Nutrition 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 1
- BVTBRVFYZUCAKH-UHFFFAOYSA-L disodium selenite Chemical compound [Na+].[Na+].[O-][Se]([O-])=O BVTBRVFYZUCAKH-UHFFFAOYSA-L 0.000 description 1
- 239000006185 dispersion Substances 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- 208000002173 dizziness Diseases 0.000 description 1
- 238000000921 elemental analysis Methods 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 235000020774 essential nutrients Nutrition 0.000 description 1
- 206010016256 fatigue Diseases 0.000 description 1
- 239000006260 foam Substances 0.000 description 1
- 238000005755 formation reaction Methods 0.000 description 1
- 125000000404 glutamine group Chemical group N[C@@H](CCC(N)=O)C(=O)* 0.000 description 1
- 239000000122 growth hormone Substances 0.000 description 1
- 230000003676 hair loss Effects 0.000 description 1
- 231100000869 headache Toxicity 0.000 description 1
- 230000002363 herbicidal effect Effects 0.000 description 1
- 239000004009 herbicide Substances 0.000 description 1
- 208000006278 hypochromic anemia Diseases 0.000 description 1
- 230000001771 impaired effect Effects 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 229910010272 inorganic material Inorganic materials 0.000 description 1
- 239000011147 inorganic material Substances 0.000 description 1
- 150000002500 ions Chemical class 0.000 description 1
- 230000007794 irritation Effects 0.000 description 1
- 231100001231 less toxic Toxicity 0.000 description 1
- 201000002364 leukopenia Diseases 0.000 description 1
- 231100001022 leukopenia Toxicity 0.000 description 1
- 244000144972 livestock Species 0.000 description 1
- 230000009401 metastasis Effects 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 230000003020 moisturizing effect Effects 0.000 description 1
- 230000020763 muscle atrophy Effects 0.000 description 1
- 201000000585 muscular atrophy Diseases 0.000 description 1
- 208000010125 myocardial infarction Diseases 0.000 description 1
- 230000008693 nausea Effects 0.000 description 1
- 231100000956 nontoxicity Toxicity 0.000 description 1
- 235000015097 nutrients Nutrition 0.000 description 1
- 235000016709 nutrition Nutrition 0.000 description 1
- 230000035764 nutrition Effects 0.000 description 1
- 208000033808 peripheral neuropathy Diseases 0.000 description 1
- 230000035479 physiological effects, processes and functions Effects 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 230000035755 proliferation Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 230000028327 secretion Effects 0.000 description 1
- 229940065287 selenium compound Drugs 0.000 description 1
- 150000003343 selenium compounds Chemical class 0.000 description 1
- 230000037370 skin discoloration Effects 0.000 description 1
- 206010041232 sneezing Diseases 0.000 description 1
- 229960001471 sodium selenite Drugs 0.000 description 1
- 239000011781 sodium selenite Substances 0.000 description 1
- 235000015921 sodium selenite Nutrition 0.000 description 1
- 230000001954 sterilising effect Effects 0.000 description 1
- 238000004659 sterilization and disinfection Methods 0.000 description 1
- FDDDEECHVMSUSB-UHFFFAOYSA-N sulfanilamide Chemical compound NC1=CC=C(S(N)(=O)=O)C=C1 FDDDEECHVMSUSB-UHFFFAOYSA-N 0.000 description 1
- 229940124530 sulfonamide Drugs 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 230000001629 suppression Effects 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 231100000701 toxic element Toxicity 0.000 description 1
- 238000003026 viability measurement method Methods 0.000 description 1
- 230000008673 vomiting Effects 0.000 description 1
Images
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C391/00—Compounds containing selenium
-
- C—CHEMISTRY; METALLURGY
- C01—INORGANIC CHEMISTRY
- C01B—NON-METALLIC ELEMENTS; COMPOUNDS THEREOF; METALLOIDS OR COMPOUNDS THEREOF NOT COVERED BY SUBCLASS C01C
- C01B19/00—Selenium; Tellurium; Compounds thereof
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F11/00—Compounds containing elements of Groups 6 or 16 of the Periodic Table
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Inorganic Chemistry (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Abstract
The present invention relates to a method for producing an organic selenium, which is a form in which inorganic selenium is reduced in toxicity and can be stably and uniformly applied by a chemical method, and a method for producing organic selenium according to the present invention comprises: (A) dissolving in water; (B) dissolving the inorganic selenium material in an ether solvent; (C) adding water to the solution of the inorganic selenium to dilute; (D) adjusting the pH to 5 to 8 by adding alkali to the diluted inorganic selenium solution; Mixing the pH-adjusted selenium solution with a solution in which the low-molecular amino acid is dissolved, and allowing the reaction to produce organic selenium.
Description
The present invention relates to a method for producing organic selenium, and more particularly, to a method for producing inorganic selenium by a chemical method, which is reduced in toxicity and can be stably and uniformly applied.
Selenium was first discovered by the Swedish chemist Vercellius in 1817 and was classified as a toxic element only before the 1950s.
The reason why selenium was recognized as a nutrient was the 1957 US National Institutes of Health Schubert's experiment with rats. Dr. Schwartz noted that rats fed with selenium-fed diets were better at cirrhosis I discovered that the probability of causing a significant drop was reported to the Institute.
Since 1978, the World Health Organization (WHO) and the Food and Agriculture Organization of the United Nations (FAO) have recognized selenium as an essential nutrient. Today, many people are selenium-rich, It is.
Selenium is also known to exhibit excellent antioxidant activity and is required for normal sperm production and inhibits the development and metastasis of cancer and is useful for preventing angina pectoris, myocardial infarction, hypertension, arteriosclerosis, cataract, arthritis, muscle atrophy, There are also reports that it is effective in declining.
However, selenium has the above advantages when there is a proper amount, but in the case of excess, irritation, sneezing, coughing, dizziness, dyspnea, headache, May cause hypochromic anemia, leukopenia, and impaired physiology. Other symptoms include nausea, vomiting, loss of hair, changes in nails, fatigue, peripheral neuropathy, skin discoloration, and calculus. Too much selenium in the blood leads to an addiction called selenium.
In humans, toxic effects have been reported in blood concentrations ranging from 0.179 μg / ㎖ to 7.5 μg / ㎖, and the Food and Nutrition Committee of the American Medical Association has set the maximum selenium dose for adults to 40 μg per day.
Although attention has been paid to the above-mentioned excellent actions of selenium, many researches have been carried out with interest on external preparations including selenium, herbicide, livestock feed, etc. However, there has been a disadvantage in not completely eliminating the toxicity of selenium.
That is, in the conventional technology for using selenium as food, medicine, feed, etc., selenium itself is mainly used as a fine powder so that uniform dispersion can not be achieved and toxicity of selenium can not be removed at a high concentration.
In addition, the organic selenium is adsorbed by a physical reaction only when the amount of the organic selenium is concentrated and used, and the synthesis of the organic selenium is made into a finely pulverized state. Therefore, a correct chemical reaction can not occur, Is not developed yet.
Disclosure of the Invention The present invention has been made to solve the problems of the prior art described above, and it is an object of the present invention to provide a method of synthesizing an organic selenium compound from inorganic selenium by a chemical method, thereby eliminating the toxicity of selenium and uniformly and safely And the like.
The method for producing organic selenium according to the present invention is characterized by comprising the following steps:
(A) dissolving a water-soluble low-molecular amino acid in water;
Dissolving selenium in an ether-based solvent (B);
(C) adding water to the selenium-dissolved solution to dilute it;
(D) adjusting the pH of the diluted inorganic selenium solution to 5 to 8;
(E) a water-soluble organic selenium is produced by mixing and reacting a solution in which pH is adjusted in step D and a solution in which a low molecular weight amino acid obtained in step A is dissolved.
According to the present invention, since the inorganic selenium is converted into the organic selenium by the chemical method, the produced organic selenium is less toxic than the inorganic selenium, and the active ingredient can be stably and uniformly penetrated into the water, It has excellent transdermal absorption and moisturizing effect, and has an excellent effect on the treatment of atopic dermatitis.
FIG. 1 is a flow chart showing a method of manufacturing organic selenium according to the present invention in order;
Figure 2 shows the IR spectrum of the product obtained through the examples;
Figure 3 is a graph of the survival rate of RAW264.7 cells in the presence of selenium aspartate prepared in the Examples;
4 shows the NO production inhibitory effect of selenium aspartate prepared in Example The graph shown;
FIG. 5 is a photograph of the state of an arm of an atopic patient; FIG.
FIG. 6 is a photograph of the state of the arm after spraying selenium aspartate in an atopic patient. FIG.
Hereinafter, a specific embodiment of the present invention will be described with reference to the accompanying drawings.
The method for producing organic selenium according to the present invention basically comprises reacting selenium dissolved in ether with water-soluble low-molecular amino acid dissolved in water to prepare water-soluble organic selenium, 1 in detail.
First, a water-soluble low-molecular amino acid is dissolved in water (A).
The water-soluble low-molecular-weight amino acid is not particularly limited, but is preferably glutamine (Glutamine) and arginine (glutamine), which promote the secretion of growth hormone and promote the synthesis of muscle protein, Lysine, Valine, Leucin, and Aspartic acid, and the like.
The water-soluble low-molecular-weight amino acid is added in an amount of 5 to 10 wt% to water, and the temperature is gradually raised to maintain the temperature at 60 to 80 ° C, vigorously stirred, and the pH is adjusted to 5 to 9. After complete dissolution, allow to cool slowly to room temperature for more than 24 hours to prevent recrystallization. If recrystallization occurs, adjust the pH so that recrystallization does not occur at room temperature.
On the other hand, an inorganic selenium material separately from the amino acid is dissolved in an ether solvent (B).
The inorganic selenium material is preferably selenium, and may be an inorganic material containing selenium such as selenic acid, selenic acid, sodium selenite, etc. as constituent elements.
The ether-based solvent is preferably diethyl ether, and the inorganic selenium material is added to the ether-based solvent and stirred for 30 to 60 minutes while maintaining the temperature at about 30 ° C, thereby completely dissolving.
Next, water is added to the inorganic selenium solution to dilute (C), and the pH of the diluted selenium solution is adjusted to 5 to 8 (D).
The amount of water added is determined by the desired concentration of selenium, and after dilution, the pH is adjusted to 5-8 by the addition of ammonia or sodium hydroxide solution. These ammonia or sodium hydroxide solutions are preferably added dropwise to the burette to prevent non-uniformity due to abrupt reaction.
Finally, the solution (A) in which the low-molecular amino acid is dissolved and the selenium solution (D) in which the pH is adjusted are mixed and reacted to produce organic selenium.
The reaction is carried out by slowly adding an aqueous solution in which a water-soluble low molecular weight amino acid is dissolved in a selenium solution while stirring, or slowly adding a selenium solution to a water-soluble low molecular weight amino acid aqueous solution while stirring.
The concentration of selenium can be adjusted to be in the range of 0.1 to 20 ppm. When mixing, the stirring is made vigorous and the pH is adjusted to 5 to 9 by titration with ammonia water or sodium hydroxide solution. The reaction temperature is in the range of 60 to 80 ° C and the reaction is carried out for 24 to 72 hours.
Hereinafter, the present invention will be described in more detail by way of examples.
Example
First, 1000 mL of commercially available sterilized distilled water (manufactured by KANTO CHEMICAL INDUSTRIAL CO., LTD.) Was adjusted to 50 DEG C, and 0.05 mol of aspartic acid (manufactured by KANTO CHEMICAL Co., Ltd.) was added while stirring for 24 hours, Was gradually added and dissolved while maintaining the temperature at 60 to 80 ° C to obtain an aqueous 0.05 M solution of aspartic acid. At this time, the pH was adjusted to be 5.
0.025 mol of selenium from KANTO CHEMICAL Co. was added to dimethyl ether and the mixture was stirred for 60 minutes while maintaining the temperature at 30 캜 to sufficiently dissolve the ether and 1,000 ml of distilled water was added thereto to prepare a 0.025 M aqueous selenium solution.
While stirring the diluent, the pH was adjusted to 6 by the slow addition of ammonia using a 25 mL burette.
The pH of the selenium solution was adjusted by adding 100 ml of the selenium solution to the beaker, and the aspartic acid solution was slowly added while stirring to prepare selenium aspartate in an aqueous solution having selenium concentrations of 0.1, 0.5 and 1 ppm, respectively. At this time, the stirring was vigorous, the pH was adjusted to 5 to 9 by titration with ammonia water, and the reaction was carried out for 24 to 72 hours while maintaining the temperature at 60 to 80 ° C.
In order to determine the production of selenium aspartate, the product obtained through the above examples was analyzed by IR spectroscopy, and the results are shown in Fig.
As shown in FIG 2, the IR spectrum is the absorption band of Se ions in ligand coordination bond with oxygen and 463㎝ 448㎝ -1 and -1 with a view to the absorption peak of the Se-O by an ionic bond with the ligand oxygen 463 cm -1 and 448 cm -1 are in the range of 400-600 cm -1 , which is the Metal-O vibration frequency indicated by Martell. In addition, the absorption peak observed in the range of -1 700㎝ Kobayashi of 600 ~ 850㎝ -1 (Kobayashi) the vibration frequency of the metal-pointed N can be considered as very weak absorption peak of the Se-N.
Therefore, it was confirmed from the IR analysis results of the product that the aspartic acid and the Se element were combined to form a selenium aspartate-type complex.
On the other hand, the results of elemental analysis using the above products are shown in Table 1 below.
As can be seen in Table 1, the total integer ratio, calculated by subtracting the two molecules of water, is the structure of C 2 H 12 N 2 O 8 Se, which is a 2: 1 combination of aspartic acid and selenium And it is consistent with the above-described IR analysis result.
Experiment
Using the selenium aspartate obtained in the above example, the cell viability and the NO production inhibitory effect were measured, and it was confirmed that the use of selenium aspartate was effective as a therapeutic agent for inflammation and safety for human use. Respectively.
Experiment 1: Measurement of cell viability (MTT assay)
(1) Material
RAW264.7 Fetal bovine serum (FBS) and penicillin-streptomycin (Dulbecco's modified Eagle medium (DMDM) were purchased from Gibco BRL (Grand Island, NE, USA) (LPS) and 2-5-diphenyltetrazolium bromide (MTT), dimethyl sulfoxide (DMSO), and sodium nitrite (NaNO2), which are isolated from bacteria. ) Were used for the test reagents of Sigma (St. Louis, Mo., USA).
(2) Culture of RAW264.7 cells
The RAW264.7 cell line, a macrophage of mouse, was cultured in DMEM containing 10% FBS and 1% penicillin-streptomycin, purchased from Korean Cell Line Bank. When cells were grown in more than 70% culture vessels, they were washed three times with phosphate buffered saline (PBS, pH 7.4, vacuum sterilization and filter) and subcultured. The cultivation of the cells was carried out at a temperature of 37 캜 in an incubator adjusted to constantly supply 5% CO 2 .
(3) Measurement of survival rate of RAW264.7 cells (MTT assay)
The MTT assay for evaluating the effect of the water soluble organic selenium produced on mouse macrophage RAW264.7 proliferation was performed as follows. First, 4 × 10 4 cells were inoculated into each well of a 96-well cell culture vessel, and the cells were cultured under conditions of 5% CO 2 and 37 ° C. After 24 hours, all of the cell culture medium was removed, and a culture medium containing organic selenium was newly added to meet the experimental purpose. After 24 hours, the culture medium was completely removed and the final concentration was 0.5 mg / ml The formazan formation reaction was induced with the adjusted MTT solution for 4 hours. The insoluble formazan was dissolved in DMSO solution, stirred for 15 minutes, and then measured for absorbance at 570 nm in an ELISA plate reader (Molecular Devices). The results were calculated as a comparison of the activity of the untreated control group and plotted in FIG.
As shown in FIG. 3, the survival rate of mouse macrophage RAW264.7 cells was maintained at 83 ~ 96.5% at 0.1 ~ 1.0 ㎍ / ㎖ in the culture conditions in which the water soluble organic selenium prepared in the Example was added. , And showed no toxicity to the cells at a level comparable to that of distilled water.
Experiment 2: Measurement of inhibitory effect of NO production
RAW264.7 cells were inoculated into a 96-well culture vessel in the same manner as in the cell viability measurement, and after 24 hours, selenium was treated at concentrations of 0, 0.1, 0.5, and 1.0 μg / ml, respectively. After 2 hours from the treatment time of the sample, LPS was added to the culture solution to give a final concentration of 1 / / ml, and NO production was induced for 20 hours.
To measure NO, the cell culture was transferred to a 1.5 ml tube, centrifuged at 1,000 rpm for 5 minutes to precipitate the residues, and 100 μl of the supernatant was transferred to a new 96-well vessel. acid in the same volume as 1% sulfanilamide and 0.1% N- [1-naphtyl] -ethylenediamine dihydrochloride], and the reaction was induced for 15 minutes at room temperature in a dark room. After measuring the absorbance at 540 nm in an ELISA plate reader Figure 4 graphically shows the amount of final NO produced in μM using a trend line curve using a NaNO 2 standard foam.
As shown in FIG. 4, the inhibitory effect of LPS-induced nitric oxide production in RAW264.7 cells was found to be 96.15% at a concentration of 1.0 μg / ml of water-soluble organic selenium, and 57.69% at 0.5 μg / % Inhibition effect and it was confirmed that it is excellent in suppression of inflammation reaction.
Experiment 3: Atopy treatment effect
A 15-year-old girl with a severe atopic appearance was sprayed with a solution of 2 ppm of selenium aspartate prepared in the above example for 5 days a day for 1 week, and the state of the arm was confirmed.
Fig. 5 is a photograph of the state of the arm before selenium aspartate spraying, and Fig. 6 is a photograph of the state after spraying for one week. As shown in FIGS. 5 and 6, it was confirmed that atopic symptoms were significantly improved by spraying selenium aspartate in a state where atopic conditions were very severe before selenium aspartate spraying.
Claims (4)
(A) dissolving a water-soluble low-molecular amino acid in water;
Dissolving selenium in an ether-based solvent (B);
(C) adding water to the selenium-dissolved solution to dilute it;
Adjusting the pH of the diluted selenium solution to 5 to 8 (D);
(E) a water-soluble organic selenium is produced by mixing and reacting a solution in which pH is adjusted in step D and a solution in which a low molecular weight amino acid obtained in step A is dissolved.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| KR1020150103788A KR101588441B1 (en) | 2015-07-22 | 2015-07-22 | Method for preparing organic selenium |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| KR1020150103788A KR101588441B1 (en) | 2015-07-22 | 2015-07-22 | Method for preparing organic selenium |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| KR101588441B1 true KR101588441B1 (en) | 2016-02-03 |
Family
ID=55355912
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| KR1020150103788A KR101588441B1 (en) | 2015-07-22 | 2015-07-22 | Method for preparing organic selenium |
Country Status (1)
| Country | Link |
|---|---|
| KR (1) | KR101588441B1 (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN113100440A (en) * | 2021-02-28 | 2021-07-13 | 韩长平 | Nano organic selenium and preparation method thereof |
Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR910002534B1 (en) * | 1982-05-28 | 1991-04-23 | 에프. 씨. 엔. 에스. 알. 엘., | Process for the preparation of selenum organic compounds |
| KR960028902A (en) | 1995-01-17 | 1996-08-17 | 성재갑 | Cosmetic composition containing selenium compound |
| KR20030077807A (en) | 2002-03-27 | 2003-10-04 | 조윤기 | External composition containing the selenium and its derivatives |
| KR20050055660A (en) * | 2005-05-18 | 2005-06-13 | 서희동 | Manufacturing method of a microorganism culture solution |
| KR20060012436A (en) * | 2004-08-03 | 2006-02-08 | 인하대학교 산학협력단 | Method for producing selenium peptide by yeast aytolysis |
| KR20100024234A (en) * | 2008-08-25 | 2010-03-05 | 김종혁 | Method for growing up mushroom with a lot of organic selenium |
-
2015
- 2015-07-22 KR KR1020150103788A patent/KR101588441B1/en active IP Right Grant
Patent Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR910002534B1 (en) * | 1982-05-28 | 1991-04-23 | 에프. 씨. 엔. 에스. 알. 엘., | Process for the preparation of selenum organic compounds |
| KR960028902A (en) | 1995-01-17 | 1996-08-17 | 성재갑 | Cosmetic composition containing selenium compound |
| KR20030077807A (en) | 2002-03-27 | 2003-10-04 | 조윤기 | External composition containing the selenium and its derivatives |
| KR20060012436A (en) * | 2004-08-03 | 2006-02-08 | 인하대학교 산학협력단 | Method for producing selenium peptide by yeast aytolysis |
| KR20050055660A (en) * | 2005-05-18 | 2005-06-13 | 서희동 | Manufacturing method of a microorganism culture solution |
| KR20100024234A (en) * | 2008-08-25 | 2010-03-05 | 김종혁 | Method for growing up mushroom with a lot of organic selenium |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN113100440A (en) * | 2021-02-28 | 2021-07-13 | 韩长平 | Nano organic selenium and preparation method thereof |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Patra et al. | Phyto-mediated biosynthesis of silver nanoparticles using the rind extract of watermelon (Citrullus lanatus) under photo-catalyzed condition and investigation of its antibacterial, anticandidal and antioxidant efficacy | |
| Jeeva et al. | Caesalpinia coriaria leaf extracts mediated biosynthesis of metallic silver nanoparticles and their antibacterial activity against clinically isolated pathogens | |
| Awan et al. | Ailanthus altissima leaf extract mediated green production of zinc oxide (ZnO) nanoparticles for antibacterial and antioxidant activity | |
| Castangia et al. | Combination of grape extract-silver nanoparticles and liposomes: A totally green approach | |
| Naganathan et al. | Green way genesis of silver nanoparticles using multiple fruit peels waste and its antimicrobial, anti-oxidant and anti-tumor cell line studies | |
| CN1104905C (en) | Novel powder compositions | |
| Priyadarshni et al. | Biochemical analysis of cultivated mushroom, Pleurotus florida and synthesis of silver nanoparticles for enhanced antimicrobial effects on clinically important human pathogens | |
| Arya et al. | Versatile biomedical potential of biosynthesized silver nanoparticles from Acacia nilotica bark. | |
| KR101588441B1 (en) | Method for preparing organic selenium | |
| Kaur et al. | Biosynthesis of zinc oxide nanoparticles via endophyte Trichoderma viride and evaluation of their antimicrobial and antioxidant properties | |
| KR101764260B1 (en) | Method for preparing aqueous nanosulfur composition for liquid fertilizer | |
| Bishoyi et al. | Recent progression of cyanobacteria and their pharmaceutical utility: an update | |
| Hashemitabar et al. | Assessment of antibacterial, antioxidant, and anticancer effects of biosynthesized silver nanoparticles using Teucrium polium extract | |
| Gao et al. | Research advances in preparation, stability, application, and possible risks of nanoselenium: focus on food and food-related fields | |
| Jagessar | Plant extracts based nanoparticles, a good perspective in the development of drugs in nanomedicine | |
| Vi et al. | Improvement of nutritional and bioactive compound production by lion's mane medicinal mushroom, Hericium erinaceus (Agaricomycetes), by spraying growth regulators | |
| Kamal et al. | Biocompatible formulations based on mycosynthesized iron oxide nanoparticles: Fabrication, characterization, and biological investigation | |
| Vivek et al. | Green synthesis and evaluation of antibacterial activity of zinc nanoparticles from Calotropis procera leaves | |
| Sajid et al. | Characterization and antibacterial properties of Eriobotrya japonica extract loaded silver-nanoparticles | |
| Renuka et al. | Antibacterial and anticancer activity of green synthesised titanium dioxide nanoparticle from Terminalia chebula | |
| Gharpure et al. | Albizia lebbeck-mediated ZnO phytosynthesis and their non-antimicrobial and biocompatibility studies | |
| Karimi et al. | Green synthesis of silver nanoparticles using pollen extract of rose flower and their antibacterial activity | |
| CN105746519A (en) | Pesticide composition containing fenoxanil and fungous proteoglycan | |
| Hulkoti et al. | Influence of physico-chemical parameters on the fabrication of silver nanoparticles using Petrea volubilis L. stem broth and its anti-microbial efficacy | |
| CN106491534A (en) | A kind of nanometer silver antimicrobial is controlled tinea pedis spraying and prepares and apply |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| E701 | Decision to grant or registration of patent right | ||
| GRNT | Written decision to grant | ||
| FPAY | Annual fee payment |
Payment date: 20181108 Year of fee payment: 4 |