CN108752359A - A kind of preparation method of protoporphyrin disodium - Google Patents
A kind of preparation method of protoporphyrin disodium Download PDFInfo
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- CN108752359A CN108752359A CN201810792131.6A CN201810792131A CN108752359A CN 108752359 A CN108752359 A CN 108752359A CN 201810792131 A CN201810792131 A CN 201810792131A CN 108752359 A CN108752359 A CN 108752359A
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- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/22—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains four or more hetero rings
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Abstract
The present invention provides a kind of preparation methods of protoporphyrin disodium, belong to organic compound synthesis field, include the following steps：Protoporphyrin, absolute methanol and the concentrated sulfuric acid under ultrasound condition to that alkyd reaction occur, protoporphyrin diester is obtained；Under ultrasound condition saponification is occurred into for protoporphyrin diester, NaOH methanol solutions and toluene, obtains protoporphyrin disodium.The present invention substitutes high temperature reflux using ultrasonic wave added, and protoporphyrin disodium is prepared, and hydrogen chloride gas need not be prepared in preparation process and is also avoided using strong toxic agents such as chloroforms, hot conditions need not be also used, simplify technique, whole process is easy to operate.
Description
Technical field
The present invention relates to organic compound synthesis technical field more particularly to a kind of preparation methods of protoporphyrin disodium.
Background technology
Protoporphyrin disodium is that the porphyrin that is connected and composed by four pyrroles is big as a member in porphyrins large family
The two groups of vinyl and two groups of sodium propionates of ring and the connection of ring surrounding are constituted, molecular weight 607.Earliest since protoporphyrin disodium has
There are liver protection, liver protection effect to be thus used for clinical treatment hypofunction of liver patient.Also there are some researches prove protoporphyrin disodium tools at present
There are resistance of hepatitis B and Hepatitis C Virus.In addition protoporphyrin disodium also has property specific to porphyrins
Matter-photosensitivities has the porphyrin meeting selective aggregation of abnormal compatibility in tumour cell surrounding some tumour cells, then
It is right with larger lethality to tumour cell that superoxide radical and singlet oxygen that excitation generates are irradiated by specific light source
Normal cell can be used for photodynamic therapy (PDT) treatment tumour without influence.
In the prior art, there are two types of synthetic methods for protoporphyrin disodium：Complete synthesizing process and semi-synthesis method.The former is with small molecule
Pyrroles and aldehyde ketone are that raw material synthesizes the big ring of porphyrin by classical Lindsey methods and Alder methods etc., and the latter is then natural
It is modified to obtain on porphyrin basis.Generally there are complex process for total synthesis method, and reaction step is more, and ultimate yield is low, product
The problems such as being not readily separated.Semi-synthetic method prepares protoporphyrin disodium often by the way of " treating different things alike ", and preparation process needs
It is carried out under conditions of high temperature reflux (50~100 DEG C).
Invention content
In consideration of it, the purpose of the present invention is to provide a kind of preparation methods of protoporphyrin disodium.Original porphin provided by the invention
The preparation method of quinoline disodium substitutes high temperature reflux using ultrasonic wave added, avoids using high temperature reflux, whole process is easy to operate.
In order to achieve the above-mentioned object of the invention, the present invention provides following technical scheme：
A kind of preparation method of protoporphyrin disodium, includes the following steps：
(1) protoporphyrin, absolute methanol and the concentrated sulfuric acid under ultrasound condition to that alkyd reaction occur, protoporphyrin diester is obtained；
(2) protoporphyrin diester, NaOH methanol solutions and toluene that the step (1) obtains are occurred under ultrasound condition
Saponification obtains protoporphyrin disodium.
Preferably, in the step (1) ultrasound condition supersonic frequency be (0,80] KHz.
Preferably, the amount ratio of protoporphyrin, absolute methanol and the concentrated sulfuric acid is 1g in the step (1)：20~40mL:0.5
~1mL.
Preferably, the temperature that alkyd reacts in the step (1) is 15~35 DEG C, time of alkyd reaction is 1~
3h。
Preferably, the quality of protoporphyrin diester and the volume ratio of NaOH methanol solutions are 0.1g in the step (2):10~
50mL, a concentration of 1mol/L of the NaOH methanol solutions.
Preferably, the ultrasonic power of ultrasound condition is 100~600W in the step (2).
Preferably, the ultrasonic time of ultrasound condition is 0.5~2.5h in the step (2).
Preferably, the preparation method of protoporphyrin includes the following steps in the step (1)：
Acetic anhydride-concentrated hydrochloric acid system and hemin are mixed and are ultrasonically treated, ferrous sulfate is then added
Deferrization is reacted, and protoporphyrin is obtained.
Preferably, the volume ratio of acetic anhydride and concentrated hydrochloric acid is 20 in the acetic anhydride-concentrated hydrochloric acid system：1, the concentrated hydrochloric acid
A concentration of 10~40%.
Preferably, the mass ratio of the acetic anhydride in the acetic anhydride-concentrated hydrochloric acid system and hemin is 5~55:1.
The present invention provides a kind of preparation methods of protoporphyrin disodium, include the following steps：By protoporphyrin, absolute methanol and
Alkyd reaction occurs under ultrasound condition for the concentrated sulfuric acid, obtains protoporphyrin diester；By protoporphyrin diester, NaOH methanol solutions and first
Under ultrasound condition saponification occurs for benzene, obtains protoporphyrin disodium.The present invention substitutes high temperature reflux using ultrasonic wave added, prepares
Protoporphyrin disodium is obtained, whole process is easy to operate, need not prepare hydrogen chloride gas and also avoid trying using the strong toxicity such as chloroform
Agent need not also use hot conditions, simplify entire technique, whole process is easy to operate.
Further, the present invention in saponification process study ultrasonic time, power and sodium hydroxide methanol by adding
Enter influence of the amount to protoporphyrin disodium, improve the yield and purity of protoporphyrin disodium, embodiment statistics indicate that, the present invention
The yield of middle protoporphyrin disodium reaches 74.1376%, and purity reaches 78.46%.
Description of the drawings
The present invention will be further described in detail below with reference to the accompanying drawings and specific embodiments.
Fig. 1 is protoporphyrin diester made from the embodiment of the present invention 1~2 in 4000~400cm of infrared wavelength-1Infrared figure
Spectrum；
Fig. 2 is protoporphyrin diester made from the embodiment of the present invention 1~2 in 2000~1400cm of infrared wavelength-1Infrared figure
Spectrum；
Fig. 3 is protoporphyrin diester made from the embodiment of the present invention 1~2 in 4000~2400cm of infrared wavelength-1Infrared figure
Spectrum；
Fig. 4 is that the present invention obtains the yield curve of protoporphyrin disodium the different saponification times；
Fig. 5 is that different ultrasonic power of the present invention obtains the yield curve of protoporphyrin disodium；
Fig. 6 is that difference NaOH methanol solution dosages of the invention obtain the yield curve of protoporphyrin disodium；
Fig. 7 is the INFRARED SPECTRUM of different hemins and the different wavelength range of protoporphyrin made from acetic anhydride additive amount
Figure.
Specific implementation mode
The present invention provides a kind of preparation methods of protoporphyrin disodium, include the following steps：
(1) protoporphyrin, absolute methanol and the concentrated sulfuric acid under ultrasound condition to that alkyd reaction occur, protoporphyrin diester is obtained；
(2) protoporphyrin diester, NaOH methanol solutions and toluene that the step (1) obtains are occurred under ultrasound condition
Saponification obtains protoporphyrin disodium.
Alkyd reaction is occurred under ultrasound condition for protoporphyrin, absolute methanol and the concentrated sulfuric acid by the present invention, obtains protoporphyrin two
Ester.In the present invention, the supersonic frequency of the ultrasound condition be preferably (0,80] KHz, more preferably [20,60] KHz.In this hair
In bright, the power of the ultrasound condition is preferably 0~400W, more preferably 100~400W.
In the present invention, the amount ratio of the protoporphyrin, absolute methanol and the concentrated sulfuric acid is preferably 1g：30mL:0.7mL.
In the present invention, the temperature of the alkyd reaction is preferably 15~35 DEG C, more preferably 20~30 DEG C, the alkyd
The time of reaction is preferably 1~3h, more preferably 1~2h.
The present invention does not have the addition sequence of the protoporphyrin, absolute methanol and the concentrated sulfuric acid special restriction, using ability
Charging sequence known to field technique personnel adds dense sulphur specifically, as first protoporphyrin is dissolved in absolute methanol
Acid.In the present invention, in the alkyd reaction process, reaction system becomes aubergine.
After the completion of alkyd reaction, alkyd reaction product is preferably rotated, is extracted, washed, revolved again by the present invention successively
It steams, recrystallize and dries, obtain protoporphyrin diester.
The present invention does not have the temperature and time of the revolving special restriction, can remove methanol completely.
In the present invention, the extractant used that extracts is preferably dichloromethane.The present invention preferably will revolving product with
It is transferred in separatory funnel after dichloromethane mixing.
In the present invention, the washing is vibrated repeatedly after distilled water is added preferably in extraction system, makes protoporphyrin diester
Positioned at the dichloromethane layer of purple.The present invention does not have special restriction to the dosage and washing times of the distilled water, can
The acid in extraction product is removed, prevents the protoporphyrin diester generated from hydrolysis occurs and generates jelly.
The present invention does not have special restriction to the temperature and time rotated again, can remove dichloromethane completely
?.
In the present invention, the solvent used that recrystallizes is preferably n-hexane.The present invention does not have the dosage of n-hexane
Special restriction.
The present invention does not have the temperature and time of the drying special restriction, can remove in protoporphyrin diester just oneself
Alkane.
In the present invention, the preparation method of the protoporphyrin preferably includes following steps：
Acetic anhydride-concentrated hydrochloric acid system and hemin are mixed and are ultrasonically treated, ferrous sulfate is then added
Deferrization is reacted, and protoporphyrin is obtained.
In the present invention, the volume ratio of acetic anhydride and concentrated hydrochloric acid is preferably 20 in the acetic anhydride-concentrated hydrochloric acid system：1；Institute
The concentration for stating concentrated hydrochloric acid is preferably 10~40%, and more preferably 20~40%.
In the present invention, the mass ratio of the acetic anhydride in the acetic anhydride-concentrated hydrochloric acid system and hemin is preferably 5
~55:1, more preferably 15~45:1, most preferably 25~35:1.
In the present invention, the acetic anhydride-concentrated hydrochloric acid system is preferably prepared under the conditions of ice-water bath.The present invention preferably will be dense
Hydrochloric acid, which is added drop-wise in acetic anhydride, prepares acetic anhydride-concentrated hydrochloric acid system.The present invention does not have the rate of the dropwise addition special restriction,
It can ensure dropwise addition.
In the present invention, the frequency of the supersound process is preferably 40~60KHz, and the power of the supersound process is preferably
The time of 250~400W, the supersound process are preferably 10~60min.
In the present invention, the mass ratio of the hemin and ferrous sulfate is preferably 1:0.1~0.8, more preferably
1:0.6~0.8.
In the present invention, the time of the deferrization reaction is preferably 0.5~2h, more preferably 0.5~1h；In the present invention
In, the deferrization reaction preferably carries out under ultrasound condition, and the ultrasound condition is consistent with above-mentioned supersound process, herein
It repeats no more.
After the completion of deferrization reaction, the pH value of deferrization reaction product is preferably adjusted to 4~6 by the present invention, centrifugation is precipitated,
The faintly acid deionized water for being 4~5 with pH value washs precipitation, deionized water continues washing, hot acetone recrystallizes and drying, obtains
Protoporphyrin.In the present invention, the pH value is preferably adjusted to 5.In the present invention, it is preferred to adjust deferrization using sodium hydroxide solution
The pH value of reaction product, the present invention do not have special restriction to the concentration and dosage of sodium hydroxide solution, can be anti-by deferrization
The pH value of product is answered to be adjusted to required range, specifically, the sodium hydroxide solution as used 4mol/L.
In the present invention, the pH value be 4~5 faintly acid deionized water wash number be preferably 2 times, it is described go from
The number that sub- water continues washing is preferably 3 times.
The concrete mode that the present invention recrystallizes the hot acetone and dries does not have special restriction, using art technology
Mode known to personnel.
After obtaining protoporphyrin diester, the present invention is by the protoporphyrin diester, NaOH methanol solutions and toluene in ultrasonic item
Saponification occurs under part, obtains protoporphyrin disodium.In the present invention, the concentration of the NaOH methanol solutions is preferably 1mol/
L, the quality of the protoporphyrin diester and the volume ratio of NaOH methanol solutions are preferably 0.1g:10~50mL, more preferably 0.1g:
20~40mL.
The present invention does not have the dosage of the toluene special restriction, and protoporphyrin diester can be made to be completely dissolved, tool
Body, as protoporphyrin diester 0.1g adds 50mL toluene.
In the present invention, the ultrasonic power of the ultrasound condition is preferably 100~600W, more preferably 200~500W, most
Preferably 300~400W.
In the present invention, the ultrasonic time of the ultrasound condition is preferably 0.5~2.5h, more preferably 1~2h, most preferably
For 1.5h.
The present invention does not have special restriction to the charging sequence of the protoporphyrin diester, NaOH methanol solutions and toluene,
Using addition sequence well known to those skilled in the art, specifically, as first by protoporphyrin diester and toluene heating item
It is mixed under part, adds NaOH methanol solutions.The present invention does not have the temperature of the heating special restriction, can make protoporphyrin
Diester is completely dissolved.
After the completion of saponification, the present invention is preferably by saponification product successively cooling precipitation protoporphyrin disodium, hydrochloric acid first
Alcoholic solution washs protoporphyrin disodium and drying, obtains protoporphyrin disodium.
In the present invention, the cooling is preferably natural cooling.
The concrete mode that the present invention washs the methanol hydrochloride solution and dries does not have special restriction, using this field
Mode known to technical staff.
The preparation method of protoporphyrin disodium provided by the invention is described in detail with reference to embodiment, but not
They can be interpreted as limiting the scope of the present invention.
Embodiment 1
With hemin and acetic anhydride quality adding proportion for 1：45, it measures in acetic anhydride to conical flask, then cold
Concentrated hydrochloric acid 1mL is slowly added dropwise in water-bath, is ultrasonically treated after 0.1g hemins are added, in 40KHz, 250W ultrasonic reaction
0.08g ferrous sulfate is added after reacting 10min in device, continues ultrasonic reaction 1h.After reaction, 4mol/L sodium hydroxides are added dropwise
It is 5 that solution, which adjusts pH value of solution, and precipitation is taken after centrifugation, and the faintly acid deionized water for being first 4 with pH value washs precipitation 2 times, then uses
Deionized water continues washing 3 times.Crude product is recrystallized with hot acetone and is purified, and protoporphyrin is obtained after drying.
0.1g protoporphyrins are dissolved with 30mL absolute methanols, are transferred in conical flask together, the 0.7mL concentrated sulfuric acids are added, super
Acoustic frequency is ultrasound 1h under 40KHz.It is observed that solution becomes aubergine in reaction process.After reaction, methanol is revolved
It evaporates.It is transferred in separatory funnel, is vibrated repeatedly after a certain amount of distilled water is added, the former porphin of generation after 30mL dichloromethane is added
Quinoline diester is located at the dichloromethane layer of purple, and washed several times with water is sour in product to remove, and prevents the protoporphyrin diester generated from water occurs
Solution generates jelly.After being spin-dried for dichloromethane, after being recrystallized with n-hexane, drying obtains protoporphyrin diester.
It weighs 0.1g protoporphyrin diester and the 1mol/ of 15mL is added after addition 50mL toluene auxiliary heating is dissolved
LNaOH methanol solutions react 1.5h in power is 200W ultrasound reactors, and protoporphyrin disodium is precipitated after cooling, with hydrochloric acid first
Alcoholic solution washs protoporphyrin disodium, and protoporphyrin disodium is obtained after drying.
Protoporphyrin disodium content is measured using standard curve-ultraviolet-visible spectrophotometry.Drying to constant weight for precise
Protoporphyrin disodium standard items 20mg, be configured to the standard mother liquor of 200mg/L with the dissolving of 1% methanol hydrochloride solution, take respectively
125, the standard mother liquor of 250,375,500,625 μ L is settled in the volumetric flask of 50mL, be configured to concentration be respectively 0.5,1,
1.5, the standard solution of 2,2.5mg/L.It is returned to zero using 1% methanol hydrochloride solution as blank, in the case where measuring wavelength, sequentially determining is not
With the absorbance of concentration standard solution, standard curve is drawn.Then in standard curve range, sequentially determining sample absorbance,
The yield of protoporphyrin disodium is calculated.
Embodiment 2
It is same as Example 1, differ only in supersonic frequency in the preparation process of protoporphyrin diester be respectively 0,20,60,
80KHz。
Infared spectrum research is carried out to protoporphyrin diester made from Examples 1 to 2, as a result as shown in Figures 1 to 3, Fig. 1 is red
Outer 4000~400cm of wavelength-1Infared spectrum, Fig. 2 be 2000~1400cm of infrared wavelength-1Infared spectrum, Fig. 3 be it is infrared
4000~2400cm of wavelength-1Infared spectrum.By Fig. 1~3 it is found that protoporphyrin diester produced by the present invention 1697~
1722cm-1All occurs faint wave crest in range, the corresponding absorption peak of this wave band is C=O characteristic peaks in ester group.By sample
The influence of the factors such as synthesis mode and itself purity, same functional group can shift.1600~1650cm-1Locate C=C features
During the presence at peak illustrates that ultrasonic action method prepares protoporphyrin dimethyl ester, different supersonic frequency processing are to the two of porphyrin ring surrounding
A C=C does not generate destruction, 3340cm-1Left and right place it is corresponding be N-H keys in porphyrin ring stretching vibration peak, the peak and
N-H keys before being esterified after deferrization in protoporphyrin, which are compared, has occurred red shift.
Embodiment 3
It is same as Example 1, differ only in the saponification time in the preparation process of protoporphyrin disodium be respectively 0.5,
1,2 and 2.5h.
The protoporphyrin disodium yield obtained to the different saponification times is measured, and the results are shown in Figure 4, can by Fig. 4
To find out, as ultrasonic time extends, there is downward trend again after first increasing in protoporphyrin disodium yield, and is 1.5h in ultrasonic time
When yield reach maximum value.The heat of the longer generation of ultrasonic time is more, and temperature will increase, and may promote to react to inverse
Direction carries out so that protoporphyrin disodium yield declines.
Embodiment 4
It is same as Example 1, differ only in power ultrasonic in the preparation process of protoporphyrin disodium be respectively 100,
300, saponification is carried out in the ultrasound reactor of 400,500 and 600W.
The protoporphyrin disodium yield that different ultrasonic power obtains is measured, the results are shown in Figure 5, can be seen by Fig. 5
Go out, with the increase of ultrasonic power, being slowly increased after first quickly increasing until smooth trend occurs in protoporphyrin disodium yield.When super
When acoustical power is 300W, protoporphyrin disodium yield reaches high value；When ultrasonic power is more than 300W, protoporphyrin disodium yield increases slow
Slowly until it is steady.
Embodiment 5
It is same as Example 1, differ only in NaOH methanol solutions in the preparation process of protoporphyrin disodium dosage be 5,
10,20,25 and 30mL.
The protoporphyrin disodium yield obtained to different NaOH methanol solutions dosages is measured, and the results are shown in Figure 6, by scheming
6 as can be seen that downward trend after first increasing is presented as sodium hydrate methanol solution dosage increases for protoporphyrin disodium yield.This
May be that can promote to react the direction to protoporphyrin disodium is generated due to increasing sodium hydrate methanol solution dosage to a certain extent
It carries out.When sodium hydrate methanol solution addition is 20mL, protoporphyrin disodium yield reaches maximum value, is further added by its dosage at this time
To improving yield also without very helping.
Embodiment 6
It is same as Example 1, differ only in the preparation process mesohemin (hemin) and acetic anhydride matter of protoporphyrin
It is respectively 1 to measure adding proportion:5,1:15,1:25,1:35 and 1:55 and 1:0, i.e. hemin.
Former porphin is prepared to hemin deferrization using infrared spectroscopic study difference hemin and acetic anhydride additive amount
The influence of quinoline, the results are shown in Figure 7, and Fig. 7 (A) is the red of different hemins and protoporphyrin made from acetic anhydride additive amount
External spectrum figure, there are six coordinate bonds for hemin porphyrin ring center iron tool, wherein four are connected with the N atoms in pyrrole ring
It connects, falling off for center iron can generate protoporphyrin structure certain influence, as shown in Fig. 7 (C), when hemin and acetic anhydride add
Dosage is 1：35 and 1：When 45, both in 3307cm-1There is small peak in place, which is considered as the flexible of N-H keys in porphyrin ring
The appearance of vibration peak, this peak also implies that falling off for porphyrin ring center iron atom, the N atoms being connect originally with iron due to deferrization with
Hydrogen atom is connected in ring.3307cm-1The peak intensity at place is weaker, thus it is speculated that may be related with substance purity itself, metal in porphyrin ring
Presence or absence and the peak of this 850nm in Fig. 7 (D) or so are closely related, and with falling off for metal, this summit occurs red
It moves.Compared with hemin standard items, ratio 1:This peak of 55 samples does not shift, but other samples are all sent out
Raw red shift, red shift 2cm-1Left and right.Also to ensure that the additive amount of above-mentioned acetic anhydride can't produce vinyl and carboxylic acid group simultaneously
What raw influence, from Fig. 7 (B) as can be seen that 1700cm-1Any offset does not occur from beginning to end for the carboxylic functional groups at place,
And 1600~1650cm-1Intermediate peak also all exists, this is the characteristic peak of carbon-carbon double bond.It finally adopts and is washed with deionized 1:
35 and 1:Then 45 sample pellets use potassium rhodanate solution to detect, find 1:The supernatant of 45 samples is non-discolouring, and 1:35 samples
Supernatant occur red, selective chlorination ferroheme and acetic anhydride additive amount are 1:45 match as the best of protoporphyrin reaction is prepared
Than.
The above is only a preferred embodiment of the present invention, it is noted that for the ordinary skill people of the art
For member, various improvements and modifications may be made without departing from the principle of the present invention, these improvements and modifications are also answered
It is considered as protection scope of the present invention.
Claims (10)
1. a kind of preparation method of protoporphyrin disodium, includes the following steps：
(1) protoporphyrin, absolute methanol and the concentrated sulfuric acid under ultrasound condition to that alkyd reaction occur, protoporphyrin diester is obtained；
(2) under ultrasound condition saponification is occurred into for protoporphyrin diester, NaOH methanol solutions and toluene that the step (1) obtains
Reaction, obtains protoporphyrin disodium.
2. preparation method according to claim 1, which is characterized in that the supersonic frequency of ultrasound condition in the step (1)
For (0,80] KHz.
3. preparation method according to claim 1 or 2, which is characterized in that protoporphyrin, absolute methanol in the step (1)
Amount ratio with the concentrated sulfuric acid is 1g：20~40mL:0.5~1mL.
4. preparation method according to claim 1 or 2, which is characterized in that the temperature of alkyd reaction is in the step (1)
15~35 DEG C, the time of the alkyd reaction is 1~3h.
5. preparation method according to claim 1, which is characterized in that in the step (2) quality of protoporphyrin diester with
The volume ratio of NaOH methanol solutions is 0.1g:10~50mL, a concentration of 1mol/L of the NaOH methanol solutions.
6. preparation method according to claim 1, which is characterized in that the ultrasonic power of ultrasound condition in the step (2)
For 100~600W.
7. preparation method according to claim 6, which is characterized in that the ultrasonic time of ultrasound condition in the step (2)
For 0.5~2.5h.
8. preparation method according to claim 1, which is characterized in that the preparation method packet of protoporphyrin in the step (1)
Include following steps：
Acetic anhydride-concentrated hydrochloric acid system and hemin are mixed and are ultrasonically treated, ferrous sulfate is then added, deferrization occurs
Reaction, obtains protoporphyrin.
9. preparation method according to claim 8, which is characterized in that in the acetic anhydride-concentrated hydrochloric acid system acetic anhydride with
The volume ratio of concentrated hydrochloric acid is 20：1, a concentration of the 10~40% of the concentrated hydrochloric acid.
10. preparation method according to claim 8 or claim 9, which is characterized in that the vinegar in the acetic anhydride-concentrated hydrochloric acid system
The mass ratio of acid anhydrides and hemin is 5~55:1.
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Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH0725877A (en) * | 1993-07-09 | 1995-01-27 | Ito Ham Kk | Production of hemin, proptoporphyrin diester and photoporphyrin disodium salt |
| CN1418880A (en) * | 2001-11-14 | 2003-05-21 | 上海金赤生物制品有限公司 | Process for preparing protoporphyrin disodium salt |
| CN105439880A (en) * | 2016-01-25 | 2016-03-30 | 延边大学 | Preparation method of calcium glycinate |
-
2018
- 2018-07-18 CN CN201810792131.6A patent/CN108752359A/en active Pending
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH0725877A (en) * | 1993-07-09 | 1995-01-27 | Ito Ham Kk | Production of hemin, proptoporphyrin diester and photoporphyrin disodium salt |
| CN1418880A (en) * | 2001-11-14 | 2003-05-21 | 上海金赤生物制品有限公司 | Process for preparing protoporphyrin disodium salt |
| CN105439880A (en) * | 2016-01-25 | 2016-03-30 | 延边大学 | Preparation method of calcium glycinate |
Non-Patent Citations (2)
| Title |
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| 聂丽: "《基础化学分级实验》", 31 January 2012, 中国科学技术大学出版社 * |
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