CN1687089A - Derivative of soldium iron chlorophyllin, preparation method and application - Google Patents
Derivative of soldium iron chlorophyllin, preparation method and application Download PDFInfo
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Abstract
The present invention relates to a preparation method of chlorophyllin derivative ferruginous sodium salt and its application for preparing health-care product and medicine for curing hypoferric anema. Said invention also provides its structure formula.
Description
Technical field:
The present invention relates to a kind of CHLOROPHYLLINE derivative derivative of soldium iron, preparation method and its usage.Can be raw material or make to have the obvious function of improving hypoferric anemia by the Chinese medicine silkworm excrement, can be used for preparing the healthcare products and the medicine for the treatment of hypoferric anemia by the CHLOROPHYLLINE derivative.
Background technology:
Hypoferric anemia is a kind of common disease, and according to World Health Organization's investigation statistics, the whole world has 2,000,000,000 populations to suffer from various degree iron deficiency approximately.Say " China resident nutrition and investigation of health conditions show; rise rapidly with the closely-related Chronic Non-Communicable Diseases morbidity of meals; trace element deficiency such as iron, vitamin A, at China's town and country ubiquity " in the article " Chinese need a meals revolution " of the Peoples Daily publication on February 14th, 2005 health ministry vice-minister king Gansu Province moral." iron deficiency is the major cause that causes China resident anaemia, average anaemia morbidity be 15.2%, 2 years old with interior infant up to 24.2%, among promptly average 4 infants an anaemia is just arranged ".The traditional Chinese medical herbal treatment anaemia has accumulated rich experience, and the successive dynasties document is all on the books.Ming Dynasty's Compendium of Material Medica is carried silkworm excrement and is controlled " married woman's metrorrhagia ", and the Song dynasty " interior through the side's of picking up any lost article from the road volume " carries a silkworm excrement and can control that " blood stasis blood is few." the wither main medicine of tongue of the record treatment deficiency of blood is that green vitriol and vinegar are forged pin sand (the ferrous and tiny iron filings of puritan filler) in Ming Dynasty's secret recipe " yellow pain imitate medicine ".The Chinese medicine silkworm excrement contains abundant chlorophyll, and Wei Kemin (CN02111428.5) once with the preparation of alkaline hydrolysis silkworm excrement method, obtained degraded product ferrisodium salt crude product, the treatment hypoferric anemia.Xu Deyu has reported metal complex, preparation method and the medicament for anti-gastric ulcer (CN99119878.6) of chlorophyll alpha degraded product copper, cobalt and zinc, has also reported chlorin e
6-methyl esters metal complex and synthetic method thereof (CN94112189.5).
The present invention carries out acid degradation, separation, extraction etc. with the Chinese medicine silkworm excrement and obtains the CHLOROPHYLLINE derivative, as CHLOROPHYLLINE a, CHLOROPHYLLINE e
6, CHLOROPHYLLINE e
4, compound such as CHLOROPHYLLINE f or dehydrogenation Ye Lv, make corresponding sodium salt respectively behind the complexing iron again, prove each compound ferrisodium salt sample, the function of the hypoferric anemia that all has clear improvement through experimentation on animals.
Summary of the invention:
The object of the invention provides a kind of CHLOROPHYLLINE derivative derivative of soldium iron.
Purpose of the present invention also provides a kind of preparation method of above-mentioned CHLOROPHYLLINE derivative derivative of soldium iron.
Another purpose of the present invention provides a kind of purposes of above-mentioned CHLOROPHYLLINE derivative derivative of soldium iron.
CHLOROPHYLLINE derivative soldium iron of the present invention has following structural formula:
Wherein, R
1=H, COONa or CH
2COONa, R
2=H or COONa, perhaps R
1And R
2=-CH (COONa) C (O)-;------singly-bound or do not have key.
CHLOROPHYLLINE derivative soldium iron of the present invention can following structural formula:
CHLOROPHYLLINE a soldium iron CHLOROPHYLLINE e
6Soldium iron CHLOROPHYLLINE e
4Soldium iron
CHLOROPHYLLINE f soldium iron dehydrogenation CHLOROPHYLLINE f soldium iron
CHLOROPHYLLINE derivative soldium iron of the present invention can be a raw material by the CHLOROPHYLLINE derivative, in polar solvent and under PH 3～4 conditions, add ferrous compound, as iron protochloride, Iron diacetate or ferrous sulfate, 40-70 ℃ of reaction 0.5-4 hour, filter, the free iron ion is removed in washing, adds 2-10%NaOH solution, and it is just dissolved, drying, wherein the mol ratio of CHLOROPHYLLINE derivative, ferrous compound and sodium hydroxide is 1: 1-5: 2-3.
Described CHLOROPHYLLINE derivative has following structural formula:
R wherein
1, R
2With------as previously mentioned.
CHLOROPHYLLINE derivative soldium iron of the present invention can be a raw material by the Chinese medicine silkworm excrement also, extracts CHLOROPHYLLINE a, is converted into CHLOROPHYLLINE e by CHLOROPHYLLINE a again
6, by CHLOROPHYLLINE e
6Be separately converted to CHLOROPHYLLINE e
4, CHLOROPHYLLINE f, CHLOROPHYLLINE f can also further be converted into dehydrogenation CHLOROPHYLLINE f.
The structural formula of above-mentioned CHLOROPHYLLINE is as follows respectively:
CHLOROPHYLLINE a CHLOROPHYLLINE e
6CHLOROPHYLLINE e
4
CHLOROPHYLLINE f dehydrogenation CHLOROPHYLLINE f
By CHLOROPHYLLINE a, CHLOROPHYLLINE e
4, CHLOROPHYLLINE e
6, CHLOROPHYLLINE f and dehydrogenation CHLOROPHYLLINE f change into CHLOROPHYLLINE a soldium iron, CHLOROPHYLLINE e respectively
4Soldium iron, CHLOROPHYLLINE e
6Soldium iron, CHLOROPHYLLINE f soldium iron and dehydrogenation CHLOROPHYLLINE f soldium iron.
The preparation method of above-mentioned soldium iron chlorophyllin can further describe as follows:
The Chinese medicine silkworm excrement is raw material, pulverizing, adds the organic polar solvent of 3-5 times of volume, soaks 2-4 hour at 50-70 ℃, filters, filter residue lixiviate 2 times again, merging filtrate, filtrate is extracted 2-3 time with the equal-volume non-polar organic solvent at 50-70 ℃, decon concentrates, and being situated between with sour water obtains CHLOROPHYLLINE a.
CHLOROPHYLLINE a is dissolved in the polar organic solvent, and with 10%～20%NaOH aqueous solution, the weightmeasurement ratio of CHLOROPHYLLINE a and described aqueous sodium hydroxide solution is 1: 50～100,40-70 ℃ of reaction 0.5-2 hour, pour in the 2-4 times of water, regulate pH3 with 5-20%HCl, precipitation is filtered drying.Obtain CHLOROPHYLLINE e
6
With CHLOROPHYLLINE e
6Be dissolved in the pyridine, reaction is 0.5-2 hour under reflux temperature, steams and removes pyridine acquisition CHLOROPHYLLINE e
4
With CHLOROPHYLLINE e
6Be dissolved in the pyridine, add the potassium hydroxide methanol solution of 10-35%, in the presence of oxygen, reacted 0.5-2 hour, under rare gas element backflow 1-3 hour then, add in the 1-3 times of volume water, transfer to pH3 with 5-20%HCl, filtering-depositing, acquisition CHLOROPHYLLINE f.
With CHLOROPHYLLINE f in lutidine backflow 10-20 hour, steam to desolventize and obtain dehydrogenation CHLOROPHYLLINE f.
With above-mentioned CHLOROPHYLLINE a, CHLOROPHYLLINE e
4, CHLOROPHYLLINE e
6, CHLOROPHYLLINE f or dehydrogenation CHLOROPHYLLINE f be dissolved in the polar organic solvent respectively, add iron protochloride, Iron diacetate or ferrous sulfate, 40-70 ℃ was reacted 1-4 hour under the pH3-4 condition, filtration, water flush away free iron ion, add 2-10%NaOH solution, it is just dissolved, and dry, obtain their ferrisodium salt respectively.
Described polarity dissolubility can be acetone, methyl alcohol, ethanol, acetonitrile, pyridine, lutidine or dimethyl sulfoxide (DMSO) etc., and described nonpolar dissolving can be ether, sherwood oil, C
6-C
18Alkane.
Method of the present invention is easy, is suitable for industrial production, and product has the function of improving hypoferric anemia through animal experiment proof, can prepare healthcare products and medicine.
Embodiment:
The present invention will be helped to understand by following embodiment, but content of the present invention can not be limited:
Adopt island rule 10AT high-pressure liquid phase instrument (HPLC) instrument to measure retention time (Rt) among the embodiment, adopt 25 * 0.4mm, the post of 5 μ m, moving phase: (1) ammonium acetate: methyl alcohol=2: 8 (V/V); (2) acetone: methyl alcohol=1: 1 (V/V); Gradient: (1) 0-15min; (2) 0-100%;
Ultraviolet spectrometer is measured the UV absorption peak, adopts Ion Spec HiRes, and the MALDI mass spectrograph is measured mass spectrum; Measure iron level with ThermoE IRIS Duo ICP emission spectrometer.
Embodiment 1
The preparation of CHLOROPHYLLINE a soldium iron;
Get Chinese medicine silkworm excrement chlorophyll extract crude product 200g, add 2 times of volume ether dissolutions, add isopyknic 36% hydrochloric acid again, reflux is 45 minutes in 40-60 ℃ of water-bath, boils off ether.Cooling, acid solution is got in 4 ℃ of placements layering of spending the night.With the pH to 3 of 40%NaOH regulator solution, there is precipitation to separate out.The leaching precipitation, washing, drying.Get blackish green CHLOROPHYLLINE a crude product.(elutriant, acetone: methyl alcohol: formic acid=50: 25: 1 V/V), gets product 7.58 grams through the silicagel column liquid chromatography (LC).
The HPLC retention time of CHLOROPHYLLINE a, the result of mass spectrum and ultraviolet spectroscopy is as follows:
The HPLC retention time is measured: the Rt=11.823 branch
MS?m/z：594(M+H+1)
+，593(M+H)
+，592(M)
+.
UVλmax(nm)：664.5，607.5，536.5，507.0，409.5。
Above-mentioned CHLOROPHYLLINE a1g is dissolved in the acetone, add the 1g ferrous sulfate 50 ℃ of reactions 3 hours, filter, washing, add 4% aqueous sodium hydroxide solution, it is just dissolved, drying, the mensuration of mass spectrum, UV spectrum and iron-holder that obtains CHLOROPHYLLINE a soldium iron 1.15g. CHLOROPHYLLINE a soldium iron is as follows:
UVλmax(nm)：666.5，623.0，396.5。
MS?m/z：649(M+H)
+，648(M)
+，647(M-H)
+，646((M-H-1)
+.
Iron-holder is measured: 6.571%.
Embodiment 2 CHLOROPHYLLINE e
6The preparation of soldium iron
Get CHLOROPHYLLINE a solid 5 grams and be dissolved in 250ml acetone, add 10%NaOH aqueous solution 25ml, place 60 ℃ of water-baths to react, insulated and stirred 1 hour is poured into after the cooling in the 700ml cold water, with the pH to 3 of 18%HCl regulator solution, has precipitation to separate out.The leaching precipitation washes with water, and drying gets CHLOROPHYLLINE e
6Solid.(elutriant, acetone: methyl alcohol: formic acid=50: 25: 1 V/V), gets CHLOROPHYLLINE e with the silicagel column liquid chromatography (LC)
6Solid 3.52g.
CHLOROPHYLLINE e
6The result of HPLC retention time, mass spectrum and ultraviolet spectroscopy as follows:
The HPLC retention time is measured: the Rt=6.465 branch.
MS?m/z：598(M+H+1)
+，597(M+H)
+，596(M+H-1)
+.
UVλmax(nm)：654.5，601.5，503.5，398。
Get CHLOROPHYLLINE e
61.4042g be dissolved in 140ml acetone, add FeCl
24H
2O 1.3832g boils off acetone in 65 ℃ of stirred in water bath reactions 3 hours, washes with water, and to there not being free iron, vacuum-drying gets blackish green CHLOROPHYLLINE e
6Close iron (II) powder 1.3539g.
Get CHLOROPHYLLINE e
6Close iron (II) powder 1.0242g, add 4%NaOH and make its dissolving fully just, vacuum-drying gets CHLOROPHYLLINE e
6Soldium iron 1.0672g.
CHLOROPHYLLINE e
6The result that the mass spectrum of soldium iron, UV spectrum and iron-holder are measured is as follows:
UVλmax(nm)：671.5，603.5，395.0。
MS?m/z：651(M+H)
+，650(M)
+，649(M-H)
+.
Iron-holder is measured: 6.679%.
Embodiment 3
CHLOROPHYLLINE e
4The preparation of soldium iron
Get the CHLOROPHYLLINE e that embodiment 1 described method makes
65g is dissolved in the 100ml pyridine, in oil bath, 115-125 ℃ of reflux 1 hour, underpressure distillation boils off pyridine, blackish green solid CHLOROPHYLLINE e
44.45g.
CHLOROPHYLLINE e
4HPLC retention time, mass spectrum and ultraviolet spectroscopy result as follows:
The HPLC retention time is measured: the Rt=6.632 branch.
MS?m/z：554(M+H+1)
+，553(M+H)
+.
UVλmax(nm)：661.5，606.0，528.0，501.5，403.5。
Get CHLOROPHYLLINE e
40.1826g be dissolved in the 40ml methyl alcohol, add FeCl
24H
2O 0.1810g, reaction is 2 hours in 70 ℃ of water-baths, boils off methyl alcohol, is washed with water to no free iron, and vacuum-drying gets blackish green CHLOROPHYLLINE e
4Close iron (II) sodium salt powder 0.1924g.
CHLOROPHYLLINE e
4The result that the mass spectrum of soldium iron, UV spectrum and iron-holder are measured is as follows:
UVλmax(nm)：671.5，612.5，395.5。
MS?m/z：607(M+H)
+，606(M)
+，605(M-H)
+，604(M-H-1)
+
Iron-holder is measured: 2.39%.
Embodiment 4
CHLOROPHYLLINE f closes the preparation of iron (II) sodium salt
Get the CHLOROPHYLLINE e that embodiment 1 described method makes
65g is dissolved in the 50ml pyridine, adds 25%KOH methanol solution 250ml, and reaction is 1 hour under logical oxygen condition, refluxes 1 hour under logical condition of nitrogen gas again.After the cooling solution is poured in the 1000ml cold water, added the pH to 3 of 18%HCl regulator solution, have precipitation to separate out.The leaching precipitation washes with water, and drying gets CHLOROPHYLLINE f.(elutriant, acetone: methyl alcohol: formic acid=50: 25: 1 V/V) gets blackish green CHLOROPHYLLINE f solid 4.15g with the silicagel column liquid chromatography (LC).
The HPLC retention time of CHLOROPHYLLINE f, mass spectrum and ultraviolet spectroscopy result are as follows:
The HPLC retention time is measured: the Rt=8.532 branch.
MS?m/z：540(M+H+1)
+，539(M+H)
+，538(M+H-1)
+.
UVλmax(nm)：653.5，599.0，501.5，398.5。
Get CHLOROPHYLLINE f 2.0055g and be dissolved in 200ml methyl alcohol, add FeCl
24H
2O 2.0540g in 70 ℃ of stirred in water bath reactions 3 hours, boils off methyl alcohol, is washed with water to no free iron, and vacuum-drying gets blackish green CHLOROPHYLLINE f and closes iron (II) powder 2.0860g.
Get CHLOROPHYLLINE f and close iron (II) powder 1.1803g, add 4%NaOH and make it dissolving, vacuum-drying gets CHLOROPHYLLINE f and closes iron (II) sodium salt 1.2983g.
CHLOROPHYLLINE f closes mass spectrum, UV spectrum and the iron-holder of iron (II) sodium salt and measures, and the result is as follows:
UVλmax(nm)：656.5，598.0，394.0。
MS?m/z：591(M+H)
+，590(M)
+，589(M-H)
+，588(M-H-1)
+
Iron-holder is measured: 3.27%.
Embodiment 5
Dehydrogenation CHLOROPHYLLINE f closes the preparation of iron (II) sodium salt
Get the CHLOROPHYLLINE f2g that embodiment method 3 makes and be dissolved in the 100ml lutidine, 180-220 ℃ was refluxed 10 hours, the pressure reducing and steaming lutidine, dehydrogenation CHLOROPHYLLINE f.(elutriant, acetone: methyl alcohol: formic acid=50: 15: 1 V/V), gets dehydrogenation CHLOROPHYLLINE f 1.8g. through the silicagel column liquid chromatography (LC)
The HPLC retention time of dehydrogenation CHLOROPHYLLINE f, the result of mass spectrum and ultraviolet spectroscopy is as follows:
HPLC, retention time: Rt=8.232 branch.
MS?m/z：538(M+H+1)+，537(M+H)+，536(M+H-1)+.
UV，λmax(nm)：655.0，503.5，354.0。
Get dehydrogenation CHLOROPHYLLINE f2.6228g, be dissolved in the 300ml methyl alcohol, add FeSO
42.7659g, in 65 ℃ of stirred in water bath reactions 4 hours, boil off methyl alcohol, be washed with water to no free iron, vacuum-drying gets blackish green dehydrogenation CHLOROPHYLLINE f and closes iron (II) powder 2.7602g.
Get 2.1043g dehydrogenation CHLOROPHYLLINE f and close iron (II) powder, add 4%NaOH, make it just to dissolve, vacuum-drying gets dehydrogenation CHLOROPHYLLINE f and closes iron (II) sodium salt 2.2367g.
The mass spectrum of dehydrogenation CHLOROPHYLLINE f soldium iron, UV spectrum and iron-holder measurement result are as follows:
UV，λmax(nm)：658.0，341.0。
MS?m/z：589(M+H)
+，588(M)
+，587(M-H)
+
Iron-holder is measured: 5.72%.
Embodiment 6
Improve the comparison animal experiment of rat hypoferric anemia
1 materials and methods
1.1 sample
Sample CHLOROPHYLLINE f closes iron (II) sodium salt (1#), CHLOROPHYLLINE e
6Close iron (II) sodium salt (2#), dehydrogenation CHLOROPHYLLINE f closes iron (II) sodium salt (3#)
1.2 laboratory animal
50 of healthy SD ablactation rats, male, body weight 55-65g is provided by laboratory animal portion of Fudan University, national laboratory animal conformity certification number: SCXK Shanghai 2002-0002.
1.3 low iron feed
Low iron feed formulation sees Table 1.
Table 1 hangs down the iron feed formulation
| Composition | ??％ | Composition | ????％ |
| Glucose (crystallization water) egg albumen powder takes off navel yellow corn powder gelatin corn oil sodium dihydrogen phosphate calcium carbonate | ??49.48 ??20.00 ??15.00 ??5.00 ??5.00 ??2.00 ??2.00 | 1. the choline chloride 60 mixed vitamin is 2. for the sodium chloride and potassium chloride mixed trace elements | ????0.50 ????0.50 ????0.27 ????0.15 ????0.10 |
1. mixed trace elements (g%): MgSO
4H
2O 73.816g ZnSO
47H
2O 19.657gMnSO
4H
2O 5.733g, CuSO
45H
2O 0.7315g, KIO
30.0625g,
2. mixed vitamin (g%): vitamin A (500,000 IU/g) 1.00g, vitamins D
3(200,000 IU/g) 0.75g, α-Vitamin E-acetate (gelatin that contains 25%VE) 12.5g, vitamin K 0.04g, vitamin 0.30g, riboflavin 0.30g, vitamins B
60.30g, calcium pantothenate 0.60g, nicotinic acid 3.00g, folic acid 0.10g, vitamins B
12(contain 0.1% vitamins B
12Gelatin) 2.00g, sucrose 79.11g.
1.4 experimental procedure
Rat is fed with low iron feed and distilled water, and adopts Rotating Stainless Steel Cage and food jar, avoids iron pollution in the experimentation.Adopt tail blood from the 3rd week beginning selected part rat, measure content of hemoglobin (Hb), be lower than 100g/L when following, measure Hb and the body weight of whole rats until most animals Hb.The anaemia rat of choosing Hb＜100g/L according to anaemia rat Hb level and body weight, is divided into 4 groups as laboratory animal at random, 8 every group, is respectively low iron control group, 1# sample sets, 2# sample sets and 3# sample sets.Each is organized rat and all continues to raise with low iron feed; Each sample sets is irritated stomach respectively and give 1#, 2#, 3# sample 1.67mg/b.w. (in elemental iron) every day, and sample solution prepares with distilled water; Low iron control group is irritated stomach and is given the equivalent distilled water.Experiment periods is 30 days, the experiment end of term, and the weighing rat body weight, and every hematological indices is measured in blood sampling.
1.5 observation index
1.5.1 oxyphorase (the high iron processes of cyaniding)
1.5.2 free former puff quinoline (spectrophotofluorimetry) in the red corpuscle
1.5.3 the weight of animals
1.6 statistical treatment
Adopt SPSS9.0 that experimental data is carried out statistical study, comprise ANOVA and Dunnettt check.
2 experimental results
2.1 sample is to the influence of hypoferric anemia rat hemoglobin content
By table 2 as seen, respectively organize content of hemoglobin there was no significant difference between rat (P＞0.05) before the experiment, test after 30 days, the content of hemoglobin of low iron control rats continues to descend, and the oxyphorase difference obviously raises before and after content of hemoglobin of 1#～3# sample sets rat and the experiment, with low iron control group comparing difference significance (P＜0.05) is arranged.
Rat hemoglobin content before and after table 2 experiment (X ± SD)
| Group | Number of animals (only) | Content of hemoglobin (g/L) | ||
| Before the experiment | After the experiment | Difference | ||
| Low iron control group 1# sample sets 2# sample sets 3# sample sets | ????8 ????8 ????8 ????8 | 71.1±10.3 65.9±6.8 66.9±7.5 67.1±7.6 | ????61.0±15.6 ????81.8±8.3 *????105.0±11.9 *????91.4±8.7 * | ????-10.1±8.5 ????15.9±7.2 *????38.1±15.6 *????24.3±9.9 * |
*Compare P＜0.05 with low iron control group
2.2 sample is to the influence of free former puff quinoline content in the hypoferric anemia rat red corpuscle
Because iron deficiency, free former puff quinoline content raises in the red corpuscle of low iron control rats, and the content of free former puff quinoline in the red corpuscle of 1# sample sets, 2# sample sets and 3# sample sets rat, with low iron control group ratio, obviously reduce, difference has significance (P＜0.05).
Free former puff quinoline content and experiment front and back body weight in the table 3 rat red corpuscle (X ± SD)
| Group | Number of animals (only) | Body weight (g) before the experiment | Experiment back body weight (g) | ????FEP(ug/L) |
| Low iron control group 1# sample sets 2# sample sets 3# sample sets | ????8 ????8 ????8 ????8 | ????118±14 ????123±16 ????117±13 ????114±19 | ????161±10 ????187±23 *????192±23 *????204±27 * | ????1020±274 ????701±145 *????636±158 *????711±122 * |
*Compare P＜0.05 with low iron control group
2.3 sample is to the influence of hypoferric anemia rat body weight
Respectively organize body weight there was no significant difference between rat (P＞0.05) before the experiment, test after 30 days, the body weight of 1# sample sets, 2# sample sets and 3# sample sets rat is pointed out apparently higher than low iron control group, additional chalybeate has alleviated iron deficiency to the disadvantageous effect that rat body weight increases, and sees Table 3.
3 conclusions
Content of hemoglobin and low iron control group are relatively behind 1#, 2#, the 3# sample sets rat experiment, obviously raise, difference has been checked significance (P＜0.05) by statistics, and the oxyphorase difference on average raises more than the 10g/L before and after the experiment, free former puff quinoline content and low iron control group ratio in the red corpuscle obviously reduce (P＜0.05) simultaneously.According to the judgment criteria of regulation in Ministry of Health's " protective foods check and evaluation technique standard ", can think that 1#, 2#, 3# sample improve the nutritional anemia function experimentation on animals positive as a result.
Claims (6)
1, a kind of CHLOROPHYLLINE derivative soldium iron, it has following structural formula:
R wherein
1=H, CH
3Or CH
2COONa; R
2=COONa; Or R
1And R
2=-CH (COONa) C (O)-;------is singly-bound or do not have key.
2, CHLOROPHYLLINE derivative soldium iron as claimed in claim 1 is characterized in that having following structural formula:
CHLOROPHYLLINE a soldium iron CHLOROPHYLLINE e
6Soldium iron CHLOROPHYLLINE e
4Soldium iron
CHLOROPHYLLINE f soldium iron dehydrogenation CHLOROPHYLLINE f soldium iron
3, a kind of preparation method of CHLOROPHYLLINE derivative soldium iron as claimed in claim 1, it is characterized in that the CHLOROPHYLLINE derivative is dissolved in the polar organic solvent, reacted 0.5-4 hour at 40-70 ℃ with ferrous compound, filter, flush away free iron ion, add the aqueous sodium hydroxide solution of 2-10%, make its dissolving, drying; The mol ratio of described CHLOROPHYLLINE derivative, ferrous compound and sodium hydroxide is 1: 1-5: 2～3; Described ferrous compound is iron protochloride, ferrous sulfate or Iron diacetate, and described CHLOROPHYLLINE derivative has following structural formula:
R wherein
1, R
2With------according to claim 1.
4, the preparation method of CHLOROPHYLLINE derivative soldium iron as claimed in claim 3 is characterized in that described CHLOROPHYLLINE derivative has following structural formula:
CHLOROPHYLLINE a CHLOROPHYLLINE e
6CHLOROPHYLLINE e
4
Or
CHLOROPHYLLINE f dehydrogenation CHLOROPHYLLINE f
5, the preparation method of CHLOROPHYLLINE derivative soldium iron as claimed in claim 3 is characterized in that the described CHLOROPHYLLINE thing that spreads out is by following (1), (1) and (2), (1)～(3), the five kinds of methods in (1)～(4) or (1)～(5) obtain:
(1) the Chinese medicine silkworm excrement of Fen Suiing adds the polar organic solvent of 3-5 times of volume, soaks 2-4 hour at 50-70 ℃, filters, and filtrate is extracted 2-3 time with the equal-volume non-polar organic solvent at 50-70 ℃ of evaporate to dryness, and Jie obtains CHLOROPHYLLINE a with sour water; Or
(2) in polar organic solvent under 40-70 ℃, CHLOROPHYLLINE a and the reaction of 10～20% aqueous sodium hydroxide solution were poured in the 2-4 times of volume water after 0.5-2 hour, regulated pH3 with 5-20%HCl, precipitation is filtered, drying obtains CHLOROPHYLLINE e
6Or
(3) CHLOROPHYLLINE e
6Be dissolved in the pyridine, reaction is 0.5-2 hour under reflux temperature, obtains CHLOROPHYLLINE e
4Or
(4) CHLOROPHYLLINE e
6Be dissolved in the pyridine, add 10～35% potassium hydroxide methanol solution, react 0.5-2 hour, under rare gas element backflow 1-3 hour then, add in the 1-3 times of volume water, transfer to pH3 with HCl, filter acquisition CHLOROPHYLLINE f; Or
(5) CHLOROPHYLLINE f is in lutidine backflow 10-20 hour, obtains dehydrogenation CHLOROPHYLLINE f;
Wherein CHLOROPHYLLINE a, CHLOROPHYLLINE e
4, CHLOROPHYLLINE e
6, CHLOROPHYLLINE f and dehydrogenation CHLOROPHYLLINE f structural formula described with claim 4.
6, a kind of purposes of CHLOROPHYLLINE derivative soldium iron as claimed in claim 1 is characterized in that being used to prepare the medicine or the healthcare products for the treatment of hypoferric anemia.
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB2005100249848A CN100443485C (en) | 2005-04-08 | 2005-04-08 | Derivative of soldium iron chlorophyllin, preparation method and application |
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|---|---|---|---|
| CNB2005100249848A CN100443485C (en) | 2005-04-08 | 2005-04-08 | Derivative of soldium iron chlorophyllin, preparation method and application |
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Cited By (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101671341B (en) * | 2009-08-25 | 2011-09-14 | 红桃开集团股份有限公司 | Preparation method of iron chlorophyll extract |
| WO2011117225A1 (en) | 2010-03-23 | 2011-09-29 | Vifor (International) Ag | Fe(iii) complex compounds for the treatment and prophylaxis of iron deficiency symptoms and iron deficiency anemias |
| WO2012130882A1 (en) | 2011-03-29 | 2012-10-04 | Vifor (International) Ag | Fe(iii) complexes for the treatment and prophylaxis of iron deficiency symptoms and iron deficiency anaemias |
| WO2012163938A1 (en) | 2011-05-31 | 2012-12-06 | Vifor (International) Ag | Fe(iii) 2,4-dioxo-1-carbonyl complexes for treatment and prophylaxis of iron deficiency symptoms and iron deficiency anaemias |
| CN103193782A (en) * | 2012-05-28 | 2013-07-10 | 复旦大学附属金山医院 | Photosensitizer sodium chlorophyllin derivatives and their preparation method and use |
| WO2014096193A1 (en) | 2012-12-21 | 2014-06-26 | Vifor (International) Ag | Fe(iii) complex compounds for the treatment and prophylaxis of iron deficiency symptoms and iron deficiency anemia |
| CN110161137A (en) * | 2019-05-21 | 2019-08-23 | 华中科技大学 | A method of measurement sodium-iron-chlorophyllin |
| EP2931728B1 (en) * | 2012-12-14 | 2020-02-19 | RMW Cho Group Limited | Chlorin derivative useful in photodynamic therapy and diagnosis |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN1090633C (en) * | 1999-10-28 | 2002-09-11 | 许德余 | Chlorophyll alpha degraded product metal complex, its preparation method and medicament for anti-gastric ulcer |
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Cited By (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101671341B (en) * | 2009-08-25 | 2011-09-14 | 红桃开集团股份有限公司 | Preparation method of iron chlorophyll extract |
| WO2011117225A1 (en) | 2010-03-23 | 2011-09-29 | Vifor (International) Ag | Fe(iii) complex compounds for the treatment and prophylaxis of iron deficiency symptoms and iron deficiency anemias |
| WO2012130882A1 (en) | 2011-03-29 | 2012-10-04 | Vifor (International) Ag | Fe(iii) complexes for the treatment and prophylaxis of iron deficiency symptoms and iron deficiency anaemias |
| WO2012163938A1 (en) | 2011-05-31 | 2012-12-06 | Vifor (International) Ag | Fe(iii) 2,4-dioxo-1-carbonyl complexes for treatment and prophylaxis of iron deficiency symptoms and iron deficiency anaemias |
| CN103193782A (en) * | 2012-05-28 | 2013-07-10 | 复旦大学附属金山医院 | Photosensitizer sodium chlorophyllin derivatives and their preparation method and use |
| CN103193782B (en) * | 2012-05-28 | 2015-10-28 | 复旦大学附属金山医院 | Photosensitizers CHLOROPHYLLINE sodium salt derivative and its production and use |
| EP2931728B1 (en) * | 2012-12-14 | 2020-02-19 | RMW Cho Group Limited | Chlorin derivative useful in photodynamic therapy and diagnosis |
| WO2014096193A1 (en) | 2012-12-21 | 2014-06-26 | Vifor (International) Ag | Fe(iii) complex compounds for the treatment and prophylaxis of iron deficiency symptoms and iron deficiency anemia |
| CN110161137A (en) * | 2019-05-21 | 2019-08-23 | 华中科技大学 | A method of measurement sodium-iron-chlorophyllin |
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| CN100443485C (en) | 2008-12-17 |
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