CN1093541C - Metalloporphyrin and production process thereof - Google Patents
Metalloporphyrin and production process thereof Download PDFInfo
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- CN1093541C CN1093541C CN98110619A CN98110619A CN1093541C CN 1093541 C CN1093541 C CN 1093541C CN 98110619 A CN98110619 A CN 98110619A CN 98110619 A CN98110619 A CN 98110619A CN 1093541 C CN1093541 C CN 1093541C
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- potassium hydroxide
- metalloporphyrin
- porphyrin
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- 238000004519 manufacturing process Methods 0.000 title claims abstract description 24
- 150000004032 porphyrins Chemical class 0.000 claims abstract description 40
- 239000010949 copper Substances 0.000 claims abstract description 22
- 238000005899 aromatization reaction Methods 0.000 claims abstract description 20
- ATNHDLDRLWWWCB-AENOIHSZSA-M chlorophyll a Chemical compound C1([C@@H](C(=O)OC)C(=O)C2=C3C)=C2N2C3=CC(C(CC)=C3C)=[N+]4C3=CC3=C(C=C)C(C)=C5N3[Mg-2]42[N+]2=C1[C@@H](CCC(=O)OC\C=C(/C)CCC[C@H](C)CCC[C@H](C)CCCC(C)C)[C@H](C)C2=C5 ATNHDLDRLWWWCB-AENOIHSZSA-M 0.000 claims abstract description 20
- OFOBLEOULBTSOW-UHFFFAOYSA-N Malonic acid Chemical compound OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 claims abstract description 17
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 claims abstract description 15
- 229910052751 metal Inorganic materials 0.000 claims abstract description 12
- 239000002184 metal Substances 0.000 claims abstract description 12
- 239000002253 acid Substances 0.000 claims abstract description 11
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 claims abstract description 10
- 229910052802 copper Inorganic materials 0.000 claims abstract description 10
- BUGBHKTXTAQXES-UHFFFAOYSA-N Selenium Chemical compound [Se] BUGBHKTXTAQXES-UHFFFAOYSA-N 0.000 claims abstract description 8
- 229910052742 iron Inorganic materials 0.000 claims abstract description 8
- 229910052711 selenium Inorganic materials 0.000 claims abstract description 8
- 239000011669 selenium Substances 0.000 claims abstract description 8
- ATJFFYVFTNAWJD-UHFFFAOYSA-N Tin Chemical compound [Sn] ATJFFYVFTNAWJD-UHFFFAOYSA-N 0.000 claims abstract description 7
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 claims abstract description 7
- 239000011135 tin Substances 0.000 claims abstract description 7
- 229910052718 tin Inorganic materials 0.000 claims abstract description 7
- 239000011701 zinc Substances 0.000 claims abstract description 7
- 229910052725 zinc Inorganic materials 0.000 claims abstract description 7
- BOTWFXYSPFMFNR-PYDDKJGSSA-N phytol Chemical group CC(C)CCC[C@@H](C)CCC[C@@H](C)CCC\C(C)=C\CO BOTWFXYSPFMFNR-PYDDKJGSSA-N 0.000 claims abstract description 6
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 claims description 95
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 claims description 66
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 claims description 42
- 238000006243 chemical reaction Methods 0.000 claims description 28
- 238000001035 drying Methods 0.000 claims description 21
- 238000000034 method Methods 0.000 claims description 20
- 230000000536 complexating effect Effects 0.000 claims description 19
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 17
- 229930002875 chlorophyll Natural products 0.000 claims description 15
- 235000019804 chlorophyll Nutrition 0.000 claims description 15
- 238000000746 purification Methods 0.000 claims description 13
- QXNVGIXVLWOKEQ-UHFFFAOYSA-N Disodium Chemical class [Na][Na] QXNVGIXVLWOKEQ-UHFFFAOYSA-N 0.000 claims description 12
- 238000003756 stirring Methods 0.000 claims description 11
- 150000001875 compounds Chemical class 0.000 claims description 9
- 238000001914 filtration Methods 0.000 claims description 9
- 238000002425 crystallisation Methods 0.000 claims description 7
- 230000008025 crystallization Effects 0.000 claims description 7
- 229910021645 metal ion Inorganic materials 0.000 claims description 7
- 238000005406 washing Methods 0.000 claims description 6
- 239000001707 (E,7R,11R)-3,7,11,15-tetramethylhexadec-2-en-1-ol Substances 0.000 claims description 5
- BLUHKGOSFDHHGX-UHFFFAOYSA-N Phytol Natural products CC(C)CCCC(C)CCCC(C)CCCC(C)C=CO BLUHKGOSFDHHGX-UHFFFAOYSA-N 0.000 claims description 5
- HNZBNQYXWOLKBA-UHFFFAOYSA-N Tetrahydrofarnesol Natural products CC(C)CCCC(C)CCCC(C)=CCO HNZBNQYXWOLKBA-UHFFFAOYSA-N 0.000 claims description 5
- BOTWFXYSPFMFNR-OALUTQOASA-N all-rac-phytol Natural products CC(C)CCC[C@H](C)CCC[C@H](C)CCCC(C)=CCO BOTWFXYSPFMFNR-OALUTQOASA-N 0.000 claims description 5
- 230000035484 reaction time Effects 0.000 claims description 5
- 229910002651 NO3 Inorganic materials 0.000 claims description 3
- NHNBFGGVMKEFGY-UHFFFAOYSA-N Nitrate Chemical compound [O-][N+]([O-])=O NHNBFGGVMKEFGY-UHFFFAOYSA-N 0.000 claims description 3
- 150000003016 phosphoric acids Chemical class 0.000 claims description 3
- 239000002994 raw material Substances 0.000 claims description 3
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 2
- 239000012535 impurity Substances 0.000 claims description 2
- 229910001510 metal chloride Inorganic materials 0.000 claims 1
- 229930002868 chlorophyll a Natural products 0.000 abstract description 6
- 241001465754 Metazoa Species 0.000 abstract description 3
- 239000008280 blood Substances 0.000 abstract description 3
- 210000004369 blood Anatomy 0.000 abstract description 3
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 abstract description 2
- 229910052749 magnesium Inorganic materials 0.000 abstract description 2
- 239000011777 magnesium Substances 0.000 abstract description 2
- 229940099898 chlorophyllin Drugs 0.000 abstract 2
- 235000019805 chlorophyllin Nutrition 0.000 abstract 2
- QRZMSCMEVNWXKY-UHFFFAOYSA-N [Na].[Na].[Cu] Chemical compound [Na].[Na].[Cu] QRZMSCMEVNWXKY-UHFFFAOYSA-N 0.000 abstract 1
- 238000010668 complexation reaction Methods 0.000 abstract 1
- ZDOYGJNADZJRFB-PVMVIUQGSA-L copper (17S,18S)-18-(2-carboxyethyl)-20-(carboxymethyl)-12-ethenyl-7-ethyl-3,8,13,17-tetramethyl-17,18-dihydroporphyrin-21,23-diide-2-carboxylic acid Chemical compound [Cu++].CCc1c(C)c2cc3[n-]c(cc4nc([C@@H](CCC(O)=O)[C@@H]4C)c(CC(O)=O)c4[n-]c(cc1n2)c(C)c4C(O)=O)c(C)c3C=C ZDOYGJNADZJRFB-PVMVIUQGSA-L 0.000 abstract 1
- 150000002739 metals Chemical class 0.000 abstract 1
- 239000000243 solution Substances 0.000 description 20
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 8
- JQRLYSGCPHSLJI-UHFFFAOYSA-N [Fe].N1C(C=C2N=C(C=C3NC(=C4)C=C3)C=C2)=CC=C1C=C1C=CC4=N1 Chemical compound [Fe].N1C(C=C2N=C(C=C3NC(=C4)C=C3)C=C2)=CC=C1C=C1C=CC4=N1 JQRLYSGCPHSLJI-UHFFFAOYSA-N 0.000 description 4
- 239000007788 liquid Substances 0.000 description 4
- NNOIMOZPWAAZRX-UHFFFAOYSA-N C12=CC=C(N1)C=C1C=CC(=N1)C=C1C=CC(N1)=CC=1C=CC(N1)=C2.[Se] Chemical compound C12=CC=C(N1)C=C1C=CC(=N1)C=C1C=CC(N1)=CC=1C=CC(N1)=C2.[Se] NNOIMOZPWAAZRX-UHFFFAOYSA-N 0.000 description 3
- SINKQSZYJSQJHN-UHFFFAOYSA-N [Sn].N1C(C=C2N=C(C=C3NC(=C4)C=C3)C=C2)=CC=C1C=C1C=CC4=N1 Chemical compound [Sn].N1C(C=C2N=C(C=C3NC(=C4)C=C3)C=C2)=CC=C1C=C1C=CC4=N1 SINKQSZYJSQJHN-UHFFFAOYSA-N 0.000 description 3
- 238000007664 blowing Methods 0.000 description 3
- 239000003814 drug Substances 0.000 description 3
- 239000000463 material Substances 0.000 description 3
- 231100000252 nontoxic Toxicity 0.000 description 3
- 230000003000 nontoxic effect Effects 0.000 description 3
- -1 porphyrin disodium salt Chemical class 0.000 description 3
- FUTVBRXUIKZACV-UHFFFAOYSA-L zinc;3-[18-(2-carboxyethyl)-8,13-bis(ethenyl)-3,7,12,17-tetramethylporphyrin-21,23-diid-2-yl]propanoic acid Chemical compound [Zn+2].[N-]1C(C=C2C(=C(C=C)C(C=C3C(=C(C=C)C(=C4)[N-]3)C)=N2)C)=C(C)C(CCC(O)=O)=C1C=C1C(CCC(O)=O)=C(C)C4=N1 FUTVBRXUIKZACV-UHFFFAOYSA-L 0.000 description 3
- PXHVJJICTQNCMI-UHFFFAOYSA-N Nickel Chemical compound [Ni] PXHVJJICTQNCMI-UHFFFAOYSA-N 0.000 description 2
- 208000007502 anemia Diseases 0.000 description 2
- ORTQZVOHEJQUHG-UHFFFAOYSA-L copper(II) chloride Chemical compound Cl[Cu]Cl ORTQZVOHEJQUHG-UHFFFAOYSA-L 0.000 description 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 2
- 239000000284 extract Substances 0.000 description 2
- 229910044991 metal oxide Inorganic materials 0.000 description 2
- 150000004706 metal oxides Chemical class 0.000 description 2
- 230000001376 precipitating effect Effects 0.000 description 2
- 229910001220 stainless steel Inorganic materials 0.000 description 2
- 239000010935 stainless steel Substances 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 239000001117 sulphuric acid Substances 0.000 description 2
- 235000011149 sulphuric acid Nutrition 0.000 description 2
- 208000036626 Mental retardation Diseases 0.000 description 1
- 241000699670 Mus sp. Species 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- OHUHAKQCZVMIOF-UHFFFAOYSA-N OS(O)(=O)=O.[SeH2] Chemical compound OS(O)(=O)=O.[SeH2] OHUHAKQCZVMIOF-UHFFFAOYSA-N 0.000 description 1
- 241000607142 Salmonella Species 0.000 description 1
- NUSORQHHEXCNQC-UHFFFAOYSA-N [Cu].N1C(C=C2N=C(C=C3NC(=C4)C=C3)C=C2)=CC=C1C=C1C=CC4=N1 Chemical compound [Cu].N1C(C=C2N=C(C=C3NC(=C4)C=C3)C=C2)=CC=C1C=C1C=CC4=N1 NUSORQHHEXCNQC-UHFFFAOYSA-N 0.000 description 1
- KKKAMDZVMJEEHQ-UHFFFAOYSA-N [Sn].[N+](=O)(O)[O-] Chemical compound [Sn].[N+](=O)(O)[O-] KKKAMDZVMJEEHQ-UHFFFAOYSA-N 0.000 description 1
- 231100000570 acute poisoning Toxicity 0.000 description 1
- 239000012670 alkaline solution Substances 0.000 description 1
- 230000036528 appetite Effects 0.000 description 1
- 235000019789 appetite Nutrition 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- 201000011510 cancer Diseases 0.000 description 1
- 239000002738 chelating agent Substances 0.000 description 1
- 229960003280 cupric chloride Drugs 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 238000011010 flushing procedure Methods 0.000 description 1
- 208000006454 hepatitis Diseases 0.000 description 1
- 231100000283 hepatitis Toxicity 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 150000002500 ions Chemical class 0.000 description 1
- NMCUIPGRVMDVDB-UHFFFAOYSA-L iron dichloride Chemical compound Cl[Fe]Cl NMCUIPGRVMDVDB-UHFFFAOYSA-L 0.000 description 1
- 238000006263 metalation reaction Methods 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 238000006386 neutralization reaction Methods 0.000 description 1
- 229910052759 nickel Inorganic materials 0.000 description 1
- BZVCUDFTTWZWPF-UHFFFAOYSA-M potassium;ethane-1,2-diol;hydroxide Chemical compound [OH-].[K+].OCCO BZVCUDFTTWZWPF-UHFFFAOYSA-M 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 230000001185 psoriatic effect Effects 0.000 description 1
- 239000000376 reactant Substances 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 238000010189 synthetic method Methods 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 229910001432 tin ion Inorganic materials 0.000 description 1
- 231100000820 toxicity test Toxicity 0.000 description 1
- NWONKYPBYAMBJT-UHFFFAOYSA-L zinc sulfate Chemical compound [Zn+2].[O-]S([O-])(=O)=O NWONKYPBYAMBJT-UHFFFAOYSA-L 0.000 description 1
- 229960001763 zinc sulfate Drugs 0.000 description 1
- 229910000368 zinc sulfate Inorganic materials 0.000 description 1
Images
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- Nitrogen Condensed Heterocyclic Rings (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention discloses a metalloporphyrin and a production process thereof, which is characterized in that: the chlorophyll-a is subjected to magnesium removal and phytol group removal to form chlorophyllin dicarboxylic acid or directly subjected to copper removal of copper disodium salt of chlorophyllin copper to obtain chlorophyllin dicarboxylic acid, then subjected to aromatization reaction to prepare free porphyrin, and added with one or other metals of zinc, tin, iron, copper and selenium to perform complexation to form 1, 3, 5, 8-tetramethyl-2, 4-diethyl-6, 7-dipropionic acid metalloporphyrin. The invention has simple and reliable production process, the cost is greatly lower than that of porphyrin extracted from animal blood, and the invention can be used for industrialized production on a certain scale, thereby solving the problem of producing metalloporphyrin by people at present.
Description
The present invention relates to metalloporphyrin series compound and its production technique, specifically produce metalloporphyrin and its production technique from chlorophyll-a or Chlorophyll Cu disodium salt.
The Application Areas of metal porphyrin complex is very extensive, for example iron porphyrin be generally acknowledge in the world prevent and treat the most effective medicine of hypoferric anemia, because its iron-holder height (9.03%), and directly be absorbed by the body and the utilization ratio height, thereby be considered to substitute the update medicine that traditional in the market inorganic salts is mended chalybeate with its molecular form; Zinc protoporphyrin and for example, human body lacks zinc can cause appetite stimulator, upgrowth and development of children is slow, mental retardation, resistibility is poor, and the easy infection disease lacks zinc and may cause dwarf and the hebetic postponement of the male sex when serious; The tin porphyrin is to cure psoriatic specific medicament; Selenium porphyrin energy cancer preventing and treating; The free porphyrin disodium salt is treated various hepatitis diseases magical curative effect ... or the like.Metal porphyrin complex is more and more paid attention to by people in a word.
The metalloporphyrin series compound is not all seen the report that the production technique aspect is arranged at home and abroad, and some scholars, expert attempt to realize with the synthetic method, but because of the processing condition complexity, cost is too high; The 2nd, with the blood extraction of animal, also because of not forming scale production.Therefore in decades, metalloporphyrin and its production technique, scientist never achieves a solution both at home and abroad.
The objective of the invention is to: provide a kind of and extract free porphyrin from chlorophyll-a or Chlorophyll Cu disodium salt, complexing becomes metalloporphyrin and production technique thereof again.
Technical scheme of the present invention is achieved in that metalloporphyrin, it is characterized in that: with the chlorophyll-a de-magging, take off become the green dicarboxylic acid of leaf or directly Chlorophyll Cu disodium salt decopper(ing) obtained the green dicarboxylic acid of leaf behind the phytol base after, carry out aromatization again, be prepared into free porphyrin, a kind of in zincification, tin, iron, copper, the selenium or other a kind of metal carry out complexing and form again, 1,3,5,8-tetramethyl--2,4-diethyl-6,7-dipropionic acid metalloporphyrin, its molecular structural formula is:
M in the molecular structural formula represents a kind of metal.
The production technique of metalloporphyrin, it is characterized in that: with the chlorophyll-a de-magging, become the green carboxylic acid of leaf after taking off the phytol base, or be the sulfuric acid decopper(ing) of 70-88% directly with Chlorophyll Cu disodium salt concentration, reaction times is 5-12 hour, again with water purification wash be 6.5-7 to pH value after, drying obtains the green dicarboxylic acid of pulvis leaf of moisture content＜20%, in the backflow of the ethylene glycol solution that contains potassium hydroxide, constantly stir then and carry out aromatization, generate 1,3,5,8-tetramethyl--2,4-diethyl-6,7-dipropionic acid porphyrin, is 1 at this green dicarboxylic acid of aromatization middle period with the weight and the volume ratio that contain the ethylene glycol solution of potassium hydroxide: 3.0-1: 8.0, temperature of reaction is 168 ℃-198 ℃, time is 5-30 hour, again with concentration for after 50-85% sulfuric acid is neutralized to PH=3-5, through being washed to PH=6.5-7, in the above-mentioned free porphyrin that obtains, add the ethylene glycol solution that contains potassium hydroxide then and make PH=8-9, add the divalent-metal ion compound again, through stirring, under the temperature about 70 ℃ complex reaction 8-12 hour, be to separate out the crystallization porphyrin after the sulfuric acid of 70-88% is neutralized to PH=5.5-5.2 with concentration again, more after filtration, washing, drying obtains the metalloporphyrin of moisture content＜5%.
Production technique of the present invention is simple and reliable, and cost also is significantly less than the porphyrin that extracts from animal blood, can be used for the suitability for industrialized production of certain scale, has solved the difficult problem that people produce metalloporphyrin at present.
Fig. 1 is the process frame chart of the production metalloporphyrin among the present invention
Fig. 2 pan of making a living belongs to the process flow sheet of an embodiment of porphyrin
The invention will be further described below in conjunction with accompanying drawing, and provide embodiment.
The production technique of the metalloporphyrin among the present invention comprises the chlorophyll-a de-magging, takes off the common process that becomes the green carboxylic acid of leaf behind the phytol base; Sulfuric acid decopper(ing), the reaction times that also can directly with Chlorophyll Cu disodium salt concentration be 70-85% are 5-12 hour, again with water purification wash to pH value be the green dicarboxylic acid pulvis of leaf that drying obtains moisture content＜20% behind the 6.5-7, in the backflow of the ethylene glycol solution that contains potassium hydroxide, carry out aromatization then, generate free porphyrin through neutralization, filtration, washing; Potassium hydroxide, ethylene glycol are analytical pure, and concentration of potassium hydroxide is 30-50% in containing the ethylene glycol solution of potassium hydroxide; How is the copper in the Chlorophyll Cu disodium salt taken off in reaction? shown in chemical equation:
When suitability for industrialized production, need use relevant devices and measuring instrument, on the basis of above-mentioned metalloporphyrin structure and manufacturing technique requirent, be specially: earlier the Chlorophyll Cu disodium salt is placed in the raw material storage device, sulfuric acid by the acid solution under meter by 1: 5-1: 7 weightmeasurement ratio enters the demetalization still respectively, preferably band stirs and temperature controlled demetalization still, enter after carrying out decopper(ing) and taking off other impurity and enter washer again after sedimentator filters, wash with the water purification in the water purification bin, and then enter drying machine, obtain the green dicarboxylic acid of leaf of moisture content＜20%, enter the aromatization still then, preferably have stirring and can carry out temperature controlled reactor, and progressively add the ethylene glycol solution contain potassium hydroxide, carry out aromatization, generate 1,3,5,8-tetramethyl--2,4-diethyl-6,7-dipropionic acid porphyrin, the potassium hydroxide of in this aromatization, using, ethylene glycol is analytical pure, concentration of potassium hydroxide in containing the ethylene glycol solution of potassium hydroxide is 30-50%, the green dicarboxylic acid of leaf is 1 with the weight and the volume ratio that contain the ethylene glycol solution of potassium hydroxide: 3.0-1: 8.0, temperature of reaction is 168 ℃-198 ℃, time 5-30 hour, be neutralized to PH=3-5 for 50-85% sulfuric acid after sedimentator filters with still concentration in then above-mentioned porphyrin being sent to, advancing washer again, to be washed till pH value with the water purification in the water purification bin be to enter the complexing still behind the 6.5-7, adding concentration in the complexing still is the potassium hydroxide solution of 30-50%, make PH=8-9, add the divalent-metal ion compound again, be specially zinc, tin, iron, copper, selenium or other nontoxic metal-salt hydrochlorate, vitriol, phosphoric acid salt, nitrate and metal oxide; Under 70 ℃ temperature complex reaction 8-12 hour, in entering again and still, with concentration is to separate out the crystallization porphyrin after the sulfuric acid of 70-88% is neutralized to PH=5.0-5.2, filters through sedimentator again, obtains the metalloporphyrin of moisture content＜5% after washer washing, the drying machine drying.
Technology of the present invention is comparatively simple, can be used for suitability for industrialized production, whole technological process safety, nontoxic and nuisanceless generation, the product yield height, and chemical structure is similar to protoheme, the metal ion height, can account for 9.03% of iron porphyrin as iron ion, zine ion can account for 10.55% of zinc protoporphyrin, selenium can account for 12.74% in the selenium porphyrin, tin ion accounts for 19.15% of tin porphyrin, and all the form with various metalloporphyrin molecular compounds directly is absorbed by the body, because with edible chlorophyll is raw material, the quality product safety non-toxic, edible absolute reliable, be example with the iron porphyrin, through the bioavailability evaluation, it is a good benefit chalybeate of preventing and treating hypoferric anemia, through toxicity test, with the dosage of 10 gram/kilograms to mice lavage, observe a week, not seeing has the acute poisoning symptom and the phenomena of mortality, and simultaneously negative through its result of Salmonella reversion test, the present invention is that metalloporphyrin has been opened up an approach with practical value for free porphyrin and complexing are provided from chlorophyll.
Provide embodiment below, all embodiment carry out under condition and the concrete parameter, and the equipment of reaction are carried out some explanations all in above-mentioned technological process.
Stir and temperature controlled stainless steel reaction pot at band, its capacity is 25 liters, stainless material is 1 network, 18 nickel, the Chlorophyll Cu disodium salt that adds 2.5kg, 1000 milliliters of sulphuric acid solns that add 75% concentration again, through decopper(ing) reaction 10 hours, filter through sedimentator then, clean to PH=7 with water purification, drying again, obtain moisture content and be 18% the green carboxylic acid 2.12kg of leaf, yield is 85%, adds 1500 milliliters potassium hydroxide ethylene glycol solution again in the reactor of the green carboxylic acid of leaf that 2.12kg is housed, and the concentration of potassium hydroxide in this solution is 35%, with the green carboxylic acid thorough mixing of leaf in the reactor, heat gradually with electrically heated and be raised to 185 ℃, carried out aromatization 20 hours, at this moment the reaction solution in the reactor is by the green redness that becomes, be that the green carboxylic acid of leaf has become free porphyrin, in entering and still, the sulfuric acid with 50% is neutralized to PH=4.5, at this moment porphyrin is separated out again, entering whizzer washes with water to PH=6.6, drying gets 1,3 again, and 5,8-tetramethyl--2,4-diethyl-6,7-dipropionic acid porphyrin 2077 gram moisture content are 20%, yield is 98%, in this aromatization, must constantly stir, according to experiment, the agitator motor rotating speed is selected 60 rev/mins for use in an embodiment, if＞60 rev/mins, it is excessive that reactant is swirl shape, if＜60 rev/mins, reaction is incomplete, along with temperature of reaction raises, produce a large amount of bubbles, the material ejection is also arranged; Blowing in the time of must be after reaction is finished ℃ in kettle temperature＞100, if be lower than 100 ℃, material is easily formed plate-like, can't blowing, blowing finishes must be clean with the hot water injection immediately in the afterreaction pot, and without flushing, failure easily induces reaction during next charging reaction; The above-mentioned 2077 gram porphyrins that obtain are put into the stainless steel complexing still of band stirring and thermometer, adding and containing concentration of potassium hydroxide is 50% ethylene glycol solution, add metal chelating agent again, as Selenium Sulphate 850 grams, through being stirred in room temperature to 70 ℃ complexing 9 hours, add concentration after complex reaction is finished and be 70% sulfuric acid and be neutralized to precipitating metal porphyrin crystallization behind the PH=5.2, enter sedimentator again and filter through being washed to PH=6.5, it is 5% selenium porphyrin that last drying obtains 2kg moisture content.
Embodiment 2
In embodiment 1 described reactor, add 3kg Chlorophyll Cu disodium salt, 1500 milliliters of sulphuric acid solns that add 85% concentration again, reacted 6 hours, filter through sedimentator then, be washed till PH=6.5 with water purification, it is 17% the green carboxylic acid 2.49kg of leaf that drying obtains moisture content, yield is 83%, adding 2000 milliliters again in the reactor that the green carboxylic acid of leaf is housed, to contain concentration of potassium hydroxide be 45% ethylene glycol solution, constantly stir, be warmed up to 175 ℃ gradually, the aromizing time is 10 hours, in entering again and still concentration be that 80% sulfuric acid is neutralized to PH=3.5, drying gets free porphyrin 2.42kg after being washed till PH=6.7 with clear water after filtration again, free porphyrin is all put into the complexing still add that to contain concentration of potassium hydroxide be 35% solution, add iron protochloride 1000 grams again, through being stirred in room temperature to 70 ℃ complexing 11 hours, add concentration after complex reaction is finished again and be after 80% sulfuric acid is neutralized to PH=5.0, the crystallization of precipitating metal porphyrin, after enter sedimentator and filter, after being washed to PH=6.8, to obtain 2.37kg moisture content be 4% iron porphyrin to drying again.
Embodiment 3
Under the condition of similar embodiment 1, carry out decopper(ing) reaction and aromatization and obtain free porphyrin 2.1kg, above-mentioned free porphyrin is put into the complexing still add that to contain concentration of potassium hydroxide be 40% solution, add nitric acid tin 870 grams again, through being stirred in room temperature to 70 ℃ complexing 10 hours, after complex reaction is finished, add concentration again and be 75% sulfuric acid and be neutralized to behind the PH=5.1 more after filtration, be washed to PH=6.6, to obtain 2.3kg moisture content be 5% tin porphyrin to drying again.
Embodiment 4
Under the condition of similar embodiment 1, carry out decopper(ing) reaction and aromatization and obtain free porphyrin 1.8kg, the 1.8kg free porphyrin is put into the complexing still add that to contain concentration of potassium hydroxide be that 43% solution adds cupric chloride again and restrains.Through being stirred in room temperature to 70 ℃ complexing 11 hours, after complex reaction is finished, add concentration again and be 85% sulfuric acid and be neutralized to behind the PH=5.0 more after filtration, be washed to PH=6.8, drying obtains 2.1kg, and moisture content is 5% copper porphyrin.
Embodiment 5
Under the condition of similar embodiment 2, carry out decopper(ing) reaction and aromatization and obtain free porphyrin 2.3kg, this porphyrin is put into the complexing still add that to contain concentration of potassium hydroxide be that 47% solution adds zinc sulfate 1000 grams again, through being stirred in room temperature to 70 ℃ complexing 10 hours, finish that to add concentration after the complex reaction again be that 70% sulfuric acid is neutralized to PH=5.2, again after filtration, be washed to PH=6.7, drying obtains 2.1kg, and moisture content is 4% zinc protoporphyrin.
Claims (5)
1, a kind of production technique of the metalloporphyrin as shown in the formula structure, it is characterized in that: become the green dicarboxylic acid of leaf with chlorophyll-α de-magging, after taking off the phytol base, or after directly Chlorophyll Cu disodium salt decopper(ing) being obtained the green dicarboxylic acid of leaf, carry out aromatization again, be prepared into free porphyrin, again a kind of metal in zincification, tin, iron, copper, the selenium carry out that complexing forms 1,3,5,8-tetramethyl--2,4-diethyl-6,7-dipropionic acid metalloporphyrin, the molecular structural formula of resulting metalloporphyrin is
M in this molecular structural formula represents a kind of metal in zinc, tin, iron, copper, the selenium.
2, production technique by the described metalloporphyrin of claim 1, it is characterized in that: with chlorophyll-α de-magging, become the green dicarboxylic acid of leaf after taking off the phytol base, or be the sulfuric acid decopper(ing) of 70-88% directly with Chlorophyll Cu disodium salt concentration, reaction times is 5-12 hour, wash to pH value 6.5-7 with water purification again, drying obtains the green dihydroxy acid of pulvis leaf of moisture content＜20%, in the backflow of the ethylene glycol solution that contains potassium hydroxide, constantly stir then and carry out aromatization, generate 1,3,5,8-tetramethyl--2,4-diethyl-6,7-dipropionic acid porphyrin, is 1 at this green dicarboxylic acid of aromatization middle period with the weight and the volume ratio that contain the ethylene glycol solution of potassium hydroxide: 3.0-1: 8.0, temperature of reaction is 168 ℃-198 ℃, time is 5-30 hour, be neutralized to PH=3-5 after be washed to PH=6.5-7 with 50-85% sulfuric acid again, the potassium hydroxide solution that adds concentration then and be 30-50% in obtaining above-mentioned free porphyrin makes PH=8-9, add the divalent-metal ion compound again, through stirring, under the temperature about 70 ℃ complex reaction 8-12 hour, more after filtration, washing, drying obtains the metalloporphyrin of moisture content＜5%.
3, by the production technique of the described metalloporphyrin of claim 2, it is characterized in that: potassium hydroxide, ethylene glycol are analytical pure, and the concentration of potassium hydroxide in containing the ethylene glycol solution of potassium hydroxide is 30-50%.
4, by the production technique of the described metalloporphyrin of claim 2, it is characterized in that: the divalent-metal ion compound is specially hydrochloride, vitriol, phosphoric acid salt, nitrate and the metal chloride of zinc, tin, iron, copper, selenium.
5, production technique by claim 1 or 2 described metalloporphyrins, it is characterized in that: earlier the Chlorophyll Cu disodium salt is placed in the raw material storage device, sulfuric acid by the acid solution under meter by 1: 5-1: 7 weightmeasurement ratio enters the demetalization still respectively, enter after carrying out decopper(ing) and taking off other impurity and enter washer again after sedimentator filters, wash with the water purification in the water purification bin, and then enter drying machine, obtain the green dicarboxylic acid of leaf of moisture content＜20%, enter the aromatization still then, and progressively add the ethylene glycol solution contain potassium hydroxide, carry out aromatization, generate 1,3,5,8-tetramethyl--2,4-diethyl-6,7-dipropionic acid porphyrin, the potassium hydroxide of in this aromatization, using, ethylene glycol is analytical pure, concentration of potassium hydroxide is 30-50% in containing the ethylene glycol solution of potassium hydroxide, the green dicarboxylic acid of leaf is 1 with the weight and the volume ratio that contain the ethylene glycol solution of potassium hydroxide: 3.0-1: 8.0, temperature of reaction is 168 ℃-198 ℃, time is 5-30 hour, be neutralized to PH=3-5 with 50-85% sulfuric acid after sedimentator filters with still in then above-mentioned porphyrin being sent to, advance again and enter the complexing still after washer is washed till PH=3-5 with the water purification in the water purification bin, in the complexing still, add the ethylene glycol solution that contains potassium hydroxide and make PH=8-9, add the divalent-metal ion compound again, under 70 ℃ temperature complex reaction 8-12 hour, in entering again and still, with concentration is to separate out the crystallization porphyrin after the sulfuric acid of 70-88% is neutralized to PH=5.0-5.2, filter through sedimentator again, washer is washed, and obtains the metalloporphyrin of moisture content＜5% after the drying machine drying.
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| CN98110619A CN1093541C (en) | 1998-01-19 | 1998-01-19 | Metalloporphyrin and production process thereof |
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| CN110156087B (en) * | 2019-05-11 | 2021-11-12 | 内蒙古师范大学 | Chalcogen compound Fe (tren) GaSbS4And method for synthesizing the same |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0196079A1 (en) * | 1985-03-25 | 1986-10-01 | The Rockefeller University | Therapeutic use of tin mesoporphyrin |
| WO1997000328A1 (en) * | 1995-06-14 | 1997-01-03 | Amresco Inc | Modified porphyroproteins |
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Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0196079A1 (en) * | 1985-03-25 | 1986-10-01 | The Rockefeller University | Therapeutic use of tin mesoporphyrin |
| WO1997000328A1 (en) * | 1995-06-14 | 1997-01-03 | Amresco Inc | Modified porphyroproteins |
Non-Patent Citations (1)
| Title |
|---|
| CHEMICAL ABSTRACS 1991.1.1 Berezim,M.B.et al * |
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