CN100534978C - New medicinal compound salt of 2,5-dihydroxy benzenes sulfonic acid and hydrate thereof - Google Patents

New medicinal compound salt of 2,5-dihydroxy benzenes sulfonic acid and hydrate thereof Download PDF

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CN100534978C
CN100534978C CNB200610131958XA CN200610131958A CN100534978C CN 100534978 C CN100534978 C CN 100534978C CN B200610131958X A CNB200610131958X A CN B200610131958XA CN 200610131958 A CN200610131958 A CN 200610131958A CN 100534978 C CN100534978 C CN 100534978C
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sulfonic acid
dihydroxy benzenes
benzenes sulfonic
hydrate
zinc
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CN101081823A (en
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黄振华
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Jilin Zhenao Pharmaceutical Co Ltd
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Shandong Xuanzhu Pharma Co Ltd
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Abstract

The present invention belongs to the field of medicine technology, discloses new stable medicinal compound salts, especially zinc magnesium salt, zinc calcium salt and magnesium calcium salt, of 2, 5-dihydroxy benzene sulfonic acid and their hydrates, and provides their preparation process and application in improving microcirculation and protecting blood vessel. The new medicinal compound salts of 2, 5-dihydroxy benzene sulfonic acid have obviously raised stability in high temperature, illuminating and high humidity and other conditions, raised dissolubility, convenient production and clinical application and broad application foreground.

Description

2, the medicinal compound salt of 5-dihydroxy benzenes sulfonic acid and hydrate thereof
1, technical field
The present invention relates to 2, the new medicinal compound salt and the hydrate thereof of 5-dihydroxy benzenes sulfonic acid, its preparation method and in the application that improves aspect capillary blood vessel circulation and the vascular protection belongs to medical technical field.
2, background technology
Dobesilate Calcium (Dobesilate Calcium) is 2, the monohydrate of 5-dihydroxy benzenes sulfonic acid calcium, be French Carroin company in Initial Public Offering in 1971, Dobesilate Calcium was written into European Pharmacopoeia in 1997, be written into British Pharmacopoeia in 1998, domesticly June calendar year 2001 this medicine introduced to the market.Dobesilate Calcium is the capillary blood vessel circulation activator or the vasoprotector of widespread use; have hypoglycemic; press down platelet aggregation; reduce pharmacological actions such as capillary permeability; the diseases such as retinopathy that diabetes are caused have obvious restraining effect and change reverse action especially, are the unique matured products of diabetic retinopathy.
The Dobesilate Calcium of existing listing is 2, and the monohydrate of 5-dihydroxy benzenes sulfonic acid calcium is an ideal disease of capillaries medicine comparatively, but it is easy to change, rotten to meet light, water absorbability is arranged, and poor stability brings great inconvenience for production, storage, circulation and use.Therefore, improve 2, the stability of the monohydrate of 5-dihydroxy benzenes sulfonic acid calcium becomes present problem demanding prompt solution.
3, summary of the invention
In order to address the above problem, the invention provides 2, the new medicinal compound salt and the hydrate thereof of 5-dihydroxy benzenes sulfonic acid, its preparation method and in the application that improves aspect capillary blood vessel circulation and the vascular protection.Of the present invention 2, pharmaceutically acceptable new medicinal compound salt medicinal compound salt of 5-dihydroxy benzenes sulfonic acid and hydrate thereof are compared with the calcium salt of listing, under the test conditions of 60 ℃ of high temperature, high humidity 92.5% and illumination 4500LX, stability has had raising extremely significantly.
Concrete technical scheme of the present invention is as follows:
The invention provides 2, pharmaceutically acceptable new medicinal compound salt of 5-dihydroxy benzenes sulfonic acid and hydrate thereof also provide the preparation method and the application of these new medicinal compound salts and hydrate thereof in addition.
The claimed compound of the present invention is 2 shown in the general formula (I), the composite salt of 5-dihydroxy benzenes sulfonic acid and hydrate thereof:
Wherein: A, B represent metallic element, all be selected from a kind of among Ca, Mg, Zn, Na, the K, but A, B are inequality;
n 1, n 2The mole number of representing A, B respectively can be any proportioning;
M1, m2 represent respectively A, B with the positive ion number;
And n 1* m1+n 2* m2=2;
N represents the number of crystal water, n=0～6.
In the above-mentioned composite salt, best with the composite salt stability of magnesium zinc, secondly be calcium zinc salt and calcium magnesium salts.Preferred composite salt of the present invention and hydrate thereof are: A, B all are selected from a kind of among Ca, Mg, the Zn, but A, B are inequality, wherein n 1+ n 2=1, m1, m2 are equal to 2, n=0～6, promptly 2,5-dihydroxy benzenes sulfonic acid magnesium zinc composite salt, 2,5-dihydroxy benzenes sulfonic acid calcium magnesium composite salt, 2,5-dihydroxy benzenes sulfonic acid calcium zinc composite salt and hydrate thereof, number n=0～6 of its crystal water are as being semihydrate, monohydrate, sesqui hydrate, dihydrate, two sesquialter hydrates, trihydrate, three sesquialter hydrates, tetrahydrate, pentahydrate, hexahydrate.
2, in the structural formula of 5-dihydroxy benzenes sulfonic acid calcium magnesium composite salt and hydrate thereof, n 1+ n 2=1, m1, m2 are equal to 2.Structural formula is as follows:
Figure C20061013195800041
2, the mole ratio of Ca and Mg can be an arbitrary proportion in the 5-dihydroxy benzenes sulfonic acid calcium magnesium composite salt, and its preferred molar number ratio is: n 1/ n 2=(0.01～100): 1, as being: 1: 100,1: 99,1: 75,1: 50,1: 30,1: 29,1: 20,1: 19,1: 18,1: 17,1: 16,1: 15,1: 14,1: 13,1: 12,1: 11,1: 10,1: 9,1: 8,1: 7,1: 6,1: 5,1: 4,1: 3,1: 2,1: 1,2: 1,3: 1,4: 1,5: 1,6: 1,7: 1,8: 1,9: 1,10: 1,11: 1,12: 1,13: 1,14: 1,15: 1,16: 1,17: 1,18: 1,19: 1,20: 1,29: 1,30: 1,50: 1,75: 1,99: 1,100: 1; Further preferred proportion is: n 1/ n 2=(0.02～50): 1, further be preferably: n 1/ n 2=(0.05～20): 1, as 1: 20,1: 19,1: 18,1: 17,1: 16,1: 15,1: 14,1: 13,1: 12,1: 11,1: 10,1: 9,1: 8,1: 7,1: 6,1: 5,1: 4,1: 3,1: 2,1: 1,2: 1,3: 1,4: 1,5: 1,6: 1,7: 1,8: 1,9: 1,10: 1,11: 1,12: 1,13: 1,14: 1,15: 1,16: 1,17: 1,18: 1,19: 1,20: 1.2,5-dihydroxy benzenes sulfonic acid calcium magnesium composite salt can be no hydrate, i.e. n=0; It also can be hydrate, number n=0～6 of its crystal water, as being semihydrate, monohydrate, sesqui hydrate, dihydrate, two sesquialter hydrates, trihydrate, three sesquialter hydrates, tetrahydrate, pentahydrate, hexahydrate etc., particularly preferred hydrate be n=n1+4n2 with the number of crystal water because n 1+ n 2=1, thus n=1+3n2, so its most preferably the number of crystal water 1～4.
2, in the structural formula of 5-dihydroxy benzenes sulfonic acid calcium zinc composite salt and hydrate thereof, n 1+ n 2=1, m1, m2 are equal to 2.Structural formula is as follows:
Figure C20061013195800051
2, the mole ratio of Ca and Zn can be an arbitrary proportion in the 5-dihydroxy benzenes sulfonic acid calcium zinc composite salt, and its preferred molar number ratio is: n 1/ n 2=(0.01～100): 1, as being: 1: 100,1: 99,1: 75,1: 50,1: 30,1: 29,1: 20,1: 19,1: 18,1: 17,1: 16,1: 15,1: 14,1: 13,1: 12,1: 11,1: 10,1: 9,1: 8,1: 7,1: 6,1: 5,1: 4,1: 3,1: 2,1: 1,2: 1,3: 1,4: 1,5: 1,6: 1,7: 1,8: 1,9: 1,10: 1,11: 1,12: 1,13: 1,14: 1,15: 1,16: 1,17: 1,18: 1,19: 1,20: 1,29: 1,30: 1,50: 1,75: 1,99: 1,100: 1; Further preferred proportion is: n 1/ n 2=(0.02～50): 1, further be preferably: n 1/ n 2=(0.05～20): 1, as 1: 20,1: 19,1: 18,1: 17,1: 16,1: 15,1: 14,1: 13,1: 12,1: 11,1: 10,1: 9,1: 8,1: 7,1: 6,1: 5,1: 4,1: 3,1: 2,1: 1,2: 1,3: 1,4: 1,5: 1,6: 1,7: 1,8: 1,9: 1,10: 1,11: 1,12: 1,13: 1,14: 1,15: 1,16: 1,17: 1,18: 1,19: 1,20: 1.2,5-dihydroxy benzenes sulfonic acid calcium zinc composite salt can be no hydrate, i.e. n=0; It also can be hydrate, number n=0～6 of its crystal water, as being semihydrate, monohydrate, sesqui hydrate, dihydrate, two sesquialter hydrates, trihydrate, three sesquialter hydrates, tetrahydrate, pentahydrate, hexahydrate etc., particularly preferred hydrate be n=n1+4n2 with the number of crystal water because n 1+ n 2=1, thus n=1+3n2, so its most preferably the number of crystal water 1～4.
2, in the structural formula of 5-dihydroxy benzenes sulfonic acid magnesium zinc composite salt and hydrate thereof, n 1+ n 2=1, m1, m2 are equal to 2.Structural formula is as follows:
Figure C20061013195800052
2, the mole ratio of Mg and Zn can be an arbitrary proportion in the 5-dihydroxy benzenes sulfonic acid magnesium zinc composite salt, all can reach effect of the present invention, and its preferred molar number ratio is: n 1/ n 2=(0.01～100): 1, as being: 1: 100,1: 99,1: 75,1: 50,1: 30,1: 29,1: 20,1: 19,1: 18,1: 17,1: 16,1: 15,1: 14,1: 13,1: 12,1: 11,1: 10,1: 9,1: 8,1: 7,1: 6,1: 5,1: 4,1: 3,1: 2,1: 1,2: 1,3: 1,4: 1,5: 1,6: 1,7: 1,8: 1,9: 1,10: 1,11: 1,12: 1,13: 1,14: 1,15: 1,16: 1,17: 1,18: 1,19: 1,20: 1,29: 1,30: 1,50: 1,75: 1,99: 1,100: 1, the composite salt of considering magnesium zinc of the present invention was as medicinal application the time, and its further preferred proportion is: n 1/ n 2=(1～100): 1, further be preferably (3～50): 1, be in particular (3～20): 1, as 3: 1,4: 1,5: 1,6: 1,7: 1,8: 1,9: 1,10: 1,11: 1,12: 1,13: 1,14: 1,15: 1,16: 1,17: 1,18: 1,19: 1,20: 1, wherein especially with 3: 1,4: 1,5: 1,6: 1,7: 1,8: 1,9: 1,10: 1,11: 1, be best at 12: 1.
2,5-dihydroxy benzenes sulfonic acid magnesium zinc composite salt can be no hydrate, i.e. n=0; It also can be hydrate, number n=0～6 of its crystal water, as being semihydrate, monohydrate, sesqui hydrate, dihydrate, two sesquialter hydrates, trihydrate, three sesquialter hydrates, tetrahydrate, pentahydrate, hexahydrate etc., particularly preferred hydrate is a tetrahydrate.
Of the present invention 2, the new composite salt of 5-dihydroxy benzenes sulfonic acid and the preparation method of hydrate thereof can for: with 2,5-dihydroxy benzenes sulfonic acid potassium exchanges through storng-acid cation exchange resin, generate 2, the 5-dihydroxy benzenes sulfonic acid aqueous solution, underpressure distillation concentrates and then charges into nitrogen, sealing is kept in Dark Place, again with 2, the 5-dihydroxy benzenes sulfonic acid aqueous solution is pressed the certain mol proportion salify with two kinds of different basic cpds, obtain 2, the medicinal compound salt that the 5-dihydroxy benzenes sulfonic acid is new or its hydrate can be made with extra care in case of necessity.Basic cpd herein is for containing Ca 2+, Mg 2+, Zn 2+, Na +, K +In the salt any two kinds, as contain Mg 2+Basic cpd can be: magnesium oxide, magnesiumcarbonate, magnesium hydroxide, Magnesium hydrogen carbonate etc. contain Zn 2+Basic cpd can be: zinc oxide, zinc carbonate, zinc hydroxide etc. contain Ca 2+Basic cpd can be calcium oxide, lime carbonate, calcium hydroxide etc., contain Na +Basic cpd can be sodium bicarbonate, yellow soda ash, sodium hydroxide etc., contain K +Basic cpd can be saleratus, salt of wormwood, potassium hydroxide etc.
Of the present invention 2, the composite salt of 5-dihydroxy benzenes sulfonic acid or its hydrate can be mixed and made into clinically arbitrary or pharmaceutically acceptable formulation with auxiliary material, preferred oral preparation or injection are applied to the patient who needs this treatment in the mode of oral or administered parenterally.
Be used for when oral, can be made into conventional solid preparation, as tablet, capsule, pill, granule etc.; Also can be made into oral liquid, as oral solution, oral suspensions, syrup etc.Tablet is based on oral ordinary tablet, and other has lozenge, Sublingual tablet, mouth paster, chewable tablet, dispersible tablet, fuse, effervescent tablet, slow releasing tablet, controlled release tablet and enteric coated tablet etc.Capsule can be divided into hard capsule (being commonly referred to as capsule), soft capsule (capsule and pill), slow releasing capsule, controlled release capsule and enteric coated capsule etc.Pill comprises dripping pill, sugar-pill, piller etc.Granule can be divided into soluble particles (being commonly referred to as particle), mix suspension grain, effervescent granule, enteric coated particles, slow-releasing granules and controlled release granule etc.
When being used for administered parenterally, can be made into injection.Injection can be divided into injection liquid, injectable sterile powder and concentrated solution for injection.Injection liquid comprises sterile solution type injection liquid, emulsion-type injection liquid, suspension type injection liquid etc., can be used for intramuscularly, intravenous injection, intravenous drip etc.Injectable sterile powder is sterilized powder or aseptic block, and available solvent crystallization, spray-drying process or freeze-drying etc. make.
Of the present invention 2, the composite salt of 5-dihydroxy benzenes sulfonic acid or the preparation of its hydrate can adopt the ordinary method production in the existing pharmacy field, can add various pharmaceutically acceptable carriers when needing.Described carrier comprises vehicle, weighting agent, tackiness agent, wetting agent, disintegrating agent, absorption enhancer, tensio-active agent, absorption carrier, lubricant of pharmaceutical field routine etc.
Of the present invention 2, the composite salt of 5-dihydroxy benzenes sulfonic acid or its hydrate are when making oral preparations, and selectable weighting agent has: starch, Icing Sugar, calcium phosphate, calcium sulfate two water things, dextrin, Microcrystalline Cellulose, lactose, pregelatinized Starch, N.F,USP MANNITOL etc.; Selectable tackiness agent has: Xylo-Mucine, PVP-K30, hydroxypropylcellulose, starch slurry, methylcellulose gum, ethyl cellulose, hypromellose, gelling starch etc.; Selectable disintegrating agent has: dry starch, polyvinylpolypyrrolidone, croscarmellose sodium, sodium starch glycolate, low-substituted hydroxypropyl cellulose etc.; Selectable lubricant has: Magnesium Stearate, talcum powder, sodium lauryl sulphate, micropowder silica gel etc.
Of the present invention 2, the composite salt of 5-dihydroxy benzenes sulfonic acid or its hydrate in order to increase its solubleness, can add solubilizing agent such as Polysorbate 80 when making injection.Can add the isotonic regulator that is used to regulate osmotic pressure in the transfusion, for example, sodium-chlor, Repone K, magnesium chloride, calcium chloride, Sodium.alpha.-hydroxypropionate, glucose, Xylitol, sorbyl alcohol and dextran etc., preferred sodium-chlor or glucose.Can add vehicle in the powder pin, for example, N.F,USP MANNITOL, glucose etc.
The present invention is further claimed above-mentioned 2, the composite salt of 5-dihydroxy benzenes sulfonic acid or its hydrate in preparation as the application in the medicine of capillary blood vessel circulation activator and vasoprotector.Of the present invention 2, the new medicinal compound salt of 5-dihydroxy benzenes sulfonic acid, especially 2,5-dihydroxy benzenes sulfonic acid magnesium zinc salt, can adjust and improve the perviousness and the fragility of capillary wall, can suppress biologically active substances such as bradykinin again. be mainly used in the disease of capillaries that the multiple reason of treatment causes, as diseases such as diabetic retinopathy, varix, phlebitis, brain spasm, pruritic dermatitises.This product bioavailability height, toxicity is lower, and the therapeutic index height is an ideal disease of capillaries medicine comparatively.
Studies show that of modern relevant magnesium, diabetes are vitamin B6, these two kinds of material wants of magnesium and cause, the people of all trouble diabetes, magnesium content in the blood is low especially, therefore Mg supplementation can reduce the requirement of health to B6, reduce the generation of toxic substance xanthurenic acid simultaneously, also should have some improvement the complication of diabetes.Studies show that of modern relevant zinc, owing to contain abundant zinc enzyme-alcoholdehydrogenase in the retina, this enzyme is participated in the metabolism of vitamin A energetically, plays an important role to keeping photoactive substance (Visual purple), and zinc concentration is up to 235 microgram/grams in the retina, occupy the hat of each tissue of whole body, therefore, scarce zinc can cause that the dark adatpation ability reduces, even causes yctalopia, at this moment only vitimin supplement A there is no effect, just can take a turn for the better rapidly and just replenish a little zinc agent.Above-mentioned research prompting, provided by the invention 2, the 5-dihydroxy benzenes sulfonic acid contains the composite salt of zinc and/or magnesium to be compared with calcium salt, and the retinopathy that diabetes are caused should have better effect.
The present invention is to above-mentioned 2, and the composite salt of 5-dihydroxy benzenes sulfonic acid and hydrate thereof have carried out physico-chemical property and Study on Stability:
Of the present invention 2, the composite salt hydrate of 5-dihydroxy benzenes sulfonic acid with gone on the market 2, the monohydrate of 5-dihydroxy benzenes sulfonic acid calcium is compared, solubleness has had obvious improvement, the results are shown in Table 1.
Table 1 solubleness relatively
Solubleness 2C 6H 5O 5S·Ca·H 2O (contrast medicine) 2C 6H 5O 5S·6/7 Mg·1/7Zn·4H 2O 2C 6H 5O 5S·6/7Ca ·1/7Zn·10/7H 2O 2C 6H 5O 5S·1/2Ca ·1/2Mg·5/2H 2O
Water Very easily dissolving Very easily dissolving Very easily dissolving Very easily dissolving
Methyl alcohol Dissolving Dissolving Dissolving Dissolving
2 of compound of the present invention and listing, 5-dihydroxy benzenes sulfonic acid calcium monohydrate is compared, and under high temperature, high humidity and strong illumination condition good especially stability is arranged.Below be 2,5-dihydroxy benzenes sulfonic acid composite salt or its hydrate and 2,5-dihydroxy benzenes sulfonic acid calcium monohydrate is placed 10 days stability result under the condition of 60 ℃ of high temperature, illumination 4500Lx, high humidity 92.5%, investigate index and be mainly proterties and content, the results are shown in Table 2.
Table 2-1 stability is 1 (10 days) relatively
Figure C20061013195800081
Table 2-2 stability is 2 (10 days) relatively
Figure C20061013195800091
Above presentation of results, the present invention 2,5-dihydroxy benzenes sulfonic acid composite salt or its hydrate and 2, the monohydrate of 5-dihydroxy benzenes sulfonic acid calcium relatively, stability has all had raising extremely significantly under conditions such as high temperature, illumination and high humidity, solved to be solved by this inventionly 2, beyond thought effect has appearred in the unsettled shortcoming of 5-dihydroxy benzenes sulfonic acid calcium.In all composite salt, best with the composite salt stability of magnesium zinc, secondly be calcium zinc salt and calcium magnesium salts.In the composite salt of magnesium zinc, the mol ratio of magnesium zinc is in (3～99): all occurred good especially stability in 1 the scope, the shared ratio of zinc is high more stable more, wherein with (3～50): 1 best, consider that the recommended intake of zinc element every day is: 10～25mg, the day recommended intake during zn deficiencie is 20～50mg, so the composite salt of magnesium zinc of the present invention as medicinal application the time, with the mol ratio of magnesium zinc in (3～20): 1 is best, as 3: 1,4: 1,5: 1,6: 1,7: 1,8: 1,9: 1,10: 1,11: 1,12: 1,13: 1,14: 1,15: 1,16: 1,17: 1,18: 1,19: 1,20: 1.
Of the present invention 2, the pharmaceutically acceptable new pharmaceutical salts of 5-dihydroxy benzenes sulfonic acid or its hydrate compared with prior art have following beyond thought advantage:
(1) provides a kind of stable 2 first, the composite salt of 5-dihydroxy benzenes sulfonic acid or its hydrate, it can be any two kinds composite salt among Ca, Mg, Zn, Na, the K, especially the composite salt stability of magnesium zinc is best, next is calcium zinc salt and calcium magnesium salts, compares with the calcium salt of listing, under the test conditions of 60 ℃ of high temperature, high humidity 92.5% and illumination 4500LX, stability has had raising extremely significantly, and solvability also increases;
(2) to 2, magnesium zinc composite salt or its hydrate of 5-dihydroxy benzenes sulfonic acid have carried out shaker test, the mol ratio of finding magnesium zinc is in (1～100): all occurred good especially stability in 1 the scope, the shared ratio of zinc is high more stable more, wherein with (1～50): 1 better, the recommended intake of considering zinc element every day is: 10～25mg, day recommended intake during zn deficiencie is 20～50mg, thus the composite salt of magnesium zinc of the present invention as medicinal application the time, with the mol ratio of magnesium zinc in (3～20): 1 is better, as 3: 1,4: 1,5: 1,6: 1,9: 1,11: 1,19: 1 etc., the optimum proportion that is suitable for making medicine was: 4: 1,5: 1,6: 1,11: 1.
(3) provide new 2 first, the composite salt that the 5-dihydroxy benzenes sulfonic acid is new or the preparation method of its hydrate, its preparation technology is simple, medicine purity height, steady quality;
(4) provided by the invention 2, the new composite salt and the hydrate thereof of 5-dihydroxy benzenes sulfonic acid, especially magnesium zinc composite salt, calcium zinc composite salt are compared with calcium salt with the calcium magnesium composite salt, and the retinopathy that diabetes are caused has better effect.
4, embodiment
The embodiment of form is described in further detail foregoing of the present invention by the following examples.But this should be interpreted as that the scope of the above-mentioned theme of the present invention only limits to following embodiment.All technology that realizes based on foregoing of the present invention all belong to scope of the present invention.The auxiliary material of each formulation can be replaced with acceptable accessories in following examples, perhaps reduces, increases.
Embodiment 12, the preparation of 5-dihydroxy benzenes sulfonic acid solution
Get 2,5-dihydroxy benzenes sulfonic acid potassium 100g (439mmol), use the 400ml water dissolution, join then in the strong acidic ion resin exchange column and exchange, collect required component 2,5-dihydroxy benzenes sulfonic acid solution, 50 ℃ of following underpressure distillation of gained solution, charge into nitrogen after being concentrated into 300ml, sealing is kept in Dark Place standby.
Embodiment 22,5-dihydroxy benzenes sulfonic acid magnesium zinc composite salt (Mg: the Zn mol ratio is 3: 1,4: 1, and 5: 1,6: 1, 7: 1,8: 1,9: 1,11: 1,12: 1,13: 1,15: 1,16: 1,18: 1,19: 1,29: 1,50: 1 Or 99: 1) preparation
It is prepared 2 to measure embodiment 1, and 5-dihydroxy benzenes sulfonic acid solution 10ml, stirring state slowly add solid oxidation magnesium and zinc oxide mix powder down (mol ratio is 4: 1,5: 1,6: 1,7: 1,8: 1,9: 1,10: 1,11: 1,12: 1,13: 1,15: 1,16: 1,18: 1,29: 1,50: 1,99: 1), stirring and dissolving, until about pH=2, reaction solution is concentrated into dried, the baby pink crude product.Crude product solid chemical compound washing with acetone filters, and solid gets pure product with silica gel adsorption in the mixing solutions of chloroform and methyl alcohol.Pure product under 1.33kPa pressure, 120 ℃ of conditions dry 24 hours 2,5-dihydroxy benzenes sulfonic acid magnesium zinc composite salt white crystalline powder.
Embodiment 32, the preparation of 5-dihydroxy benzenes sulfonic acid magnesium zinc double salt (Mg: the Zn mol ratio is 3: 1)
It is prepared 2 to measure embodiment 1, and 5-dihydroxy benzenes sulfonic acid solution 10ml, stirring state slowly add solid oxidation magnesium and zinc oxide mix powder (mol ratio is 3: 1) down, stirring and dissolving, until about pH=2, reaction solution is concentrated into dried, the baby pink crude product.Crude product solid chemical compound washing with acetone filters, solid in the mixing solutions of chloroform and methyl alcohol with silica gel adsorption by refining pure product.Pure product under 1.33kPa pressure, 120 ℃ of conditions dry 24 hours 2,5-dihydroxy benzenes sulfonic acid magnesium zinc composite salt (Mg: the Zn mol ratio is 3: 1) white crystalline powder.
Content: 99.6%
Ultimate analysis (2C 6H 5O 5S3/4Mg1/4Zn):
Molecular weight: 412.90
Measured value: C, 34.85%; H, 2.42%; Mg, 4.44%; S, 15.51%; Zn, 3.98%
Theoretical value: C, 34.91%; H, 2.44%; Mg, 4.41%; S, 15.53%; Zn, 3.96%
1H-NMR(600MHz，CDCl 3)：δ：5.02(4H，w)，6.61(2H，d)，6.87(2H，d)，7.23(2H，s)
IR(KBr)cm -1：3052，1973，1766，1623，1188，751，698
Embodiment 42, the preparation of 5-dihydroxy benzenes sulfonic acid magnesium zinc double salt (Mg: the Zn mol ratio is 3: 1) tetrahydrate
It is prepared 2 to measure embodiment 1, and 5-dihydroxy benzenes sulfonic acid solution 10ml, stirring state slowly add solid oxidation magnesium and zinc oxide mix powder (mol ratio is 3: 1) down, stirring and dissolving, until about pH=2, reaction solution is concentrated into dried, the baby pink crude product.Crude product solid chemical compound washing with acetone filters, solid in the mixing solutions of chloroform and methyl alcohol with silica gel adsorption by refining pure product.Pure product under 1.33kPa pressure, 80 ℃ of conditions dry 4 hours 2,5-dihydroxy benzenes sulfonic acid magnesium zinc composite salt tetrahydrate (Mg: the Zn mol ratio is 3: 1) white crystalline powder.
Content: 99.8%
Ultimate analysis (2C 6H 5O 5S3/4Mg1/4Zn4H 2O):
Molecular weight: 484.98
Measured value: C, 29.70%; H, 3.69%; Mg, 3.80%; S, 13.27%; Zn, 2.35%
Theoretical value: C, 29.72%; H, 3.74%; Mg, 3.76%; S, 13.22%; Zn, 3.37%
1H-NMR(600MHz，CDCl 3)：δ：5.03(4H，w)，6.67(2H，d)，6.87(2H，d)，7.29(2H，s)
IR(KBr)cm -1：3055，1977，1766，1629，1187，758，706
Thermogravimetric differential thermal analysis (2C 6H 5O 5S3/4Mg1/4Zn4H 2O):
Compound is amounted to four crystal water 100 ℃～200 ℃ weightlessness 14.90%.
Embodiment 52, the preparation of 5-dihydroxy benzenes sulfonic acid magnesium zinc double salt (Mg: the Zn mol ratio is 4: 1)
It is prepared 2 to measure embodiment 1, and 5-dihydroxy benzenes sulfonic acid solution 10ml, stirring state slowly add solid oxidation magnesium and zinc oxide mix powder (mol ratio is 4: 1) down, stirring and dissolving, until about pH=2, reaction solution is concentrated into dried, the baby pink crude product.Crude product solid chemical compound washing with acetone filters, solid in the mixing solutions of chloroform and methyl alcohol with silica gel adsorption by refining pure product.Pure product under 1.33kPa pressure, 120 ℃ of conditions dry 24 hours 2,5-dihydroxy benzenes sulfonic acid magnesium zinc composite salt (Mg: the Zn mol ratio is 4: 1) white crystalline powder.
Content: 99.6%
Ultimate analysis (2C 6H 5O 5S4/5Mg1/5Zn):
Molecular weight: 410.86
Measured value: C, 35.11%; H, 2.42%; Mg, 4.69%; S, 15.64%; Zn, 3.19%
Theoretical value: C, 35.08%; H, 2.45%; Mg, 4.73%; S, 15.61%; Zn, 3.18%
1H-NMR(600MHz，CDCl 3)：δ：5.02(4H，w)，6.61(2H，d)，6.87(2H，d)，7.23(2H，s)
IR(KBr)cm -1：3052，1973，1766，1623，1188，751，698
Embodiment 62, the preparation of 5-dihydroxy benzenes sulfonic acid magnesium zinc double salt (Mg: the Zn mol ratio is 4: 1) tetrahydrate
It is prepared 2 to measure embodiment 1, and 5-dihydroxy benzenes sulfonic acid solution 10ml, stirring state slowly add solid oxidation magnesium and zinc oxide mix powder (mol ratio is 4: 1) down, stirring and dissolving, until about pH=2, reaction solution is concentrated into dried, the baby pink crude product.Crude product solid chemical compound washing with acetone filters, solid in the mixing solutions of chloroform and methyl alcohol with silica gel adsorption by refining pure product.Pure product under 1.33kPa pressure, 80 ℃ of conditions dry 4 hours 2,5-dihydroxy benzenes sulfonic acid magnesium zinc composite salt tetrahydrate (Mg: the Zn mol ratio is 4: 1) white crystalline powder.
Content: 99.8%
Ultimate analysis (2C 6H 5O 5S4/5Mg1/5Zn4H 2O):
Molecular weight: 482.92
Measured value: C, 29.96%; H, 3.58%; Mg, 3.94%; S, 13.37%; Zn, 2.62%
Theoretical value: C, 29.85%; H, 3.76%; Mg, 4.03%; S, 13.28%; Zn, 2.71%
1H-NMR(600MHz，CDCl 3)：δ：5.03(4H，w)，6.67(2H，d)，6.87(2H，d)，7.29(2H，s)
IR(KBr)cm -1：3055，1977，1766，1629，1187，758，706
Thermogravimetric differential thermal analysis (2C 6H 5O 5S4/5Mg1/5Zn4H 2O):
Compound is amounted to four crystal water 100 ℃～200 ℃ weightlessness 14.95%.
Embodiment 72, the preparation of 5-dihydroxy benzenes sulfonic acid magnesium zinc double salt (Mg: the Zn mol ratio is 5: 1)
It is prepared 2 to measure embodiment 1, and 5-dihydroxy benzenes sulfonic acid solution 10ml, stirring state slowly add solid oxidation magnesium and zinc oxide mix powder (mol ratio is 5: 1) down, stirring and dissolving, until about pH=2, reaction solution is concentrated into dried, the baby pink crude product.Crude product solid chemical compound washing with acetone filters, solid in the mixing solutions of chloroform and methyl alcohol with silica gel adsorption by refining pure product.Pure product under 1.33kPa pressure, 120 ℃ of conditions dry 24 hours 2,5-dihydroxy benzenes sulfonic acid magnesium zinc composite salt (Mg: the Zn mol ratio is 5: 1) white crystalline powder.
Content: 99.7%
Ultimate analysis (2C 6H 5O 5S5/6Mg1/6Zn):
Molecular weight: 409.48
Measured value: C, 35.16%; H, 2.54%; Mg, 4.92%; S, 15.64%; Zn, 2.62%
Theoretical value: C, 35.20%; H, 2.46%; Mg, 4.95%; S, 15.66%; Zn, 2.66%
1H-NMR(600MHz，CDCl 3)：δ：5.04(4H，w)，6.63(2H，d)，6.90(2H，d)，7.27(2H，s)
IR(KBr)cm -1：3051，1977，1769，1628，1187，756，701
Embodiment 82, the preparation of 5-dihydroxy benzenes sulfonic acid magnesium zinc double salt (Mg: the Zn mol ratio is 5: 1) tetrahydrate
It is prepared 2 to measure embodiment 1, and 5-dihydroxy benzenes sulfonic acid solution 10ml, stirring state slowly add solid oxidation magnesium and zinc oxide mix powder (mol ratio is 5: 1) down, stirring and dissolving, until about pH=2, reaction solution is concentrated into dried, the baby pink crude product.Crude product solid chemical compound washing with acetone filters, solid in the mixing solutions of chloroform and methyl alcohol with silica gel adsorption by refining pure product.Pure product under 1.33kPa pressure, 80 ℃ of conditions dry 4 hours 2,5-dihydroxy benzenes sulfonic acid magnesium zinc composite salt tetrahydrate (Mg: the Zn mol ratio is 5: 1) white crystalline powder.
Content: 99.6%
Ultimate analysis (2C 6H 5O 5S5/6Mg1/6Zn4H 2O):
Molecular weight: 481.55
Measured value: C, 33.67%; H, 2.89%; Mg, 4.75%; S, 14.97%; Zn, 2.52%
Theoretical value: C, 29.93%; H, 3.77%; Mg, 4.21%; S, 13.32%; Zn, 2.26%
1H-NMR(600MHz，CDCl 3)：δ：5.05(4H，w)，6.65(2H，d)，6.84(2H，d)，7.30(2H，s)
IR(KBr)cm -1：3051，1974，1763，1620，1195，751，703
Thermogravimetric differential thermal analysis (2C 6H 5O 5S5/6Mg1/6Zn4H 2O):
Compound is amounted to four crystal water 100 ℃～200 ℃ weightlessness 14.53%.
Embodiment 92, the preparation of 5-dihydroxy benzenes sulfonic acid magnesium zinc composite salt (Mg: the Zn mol ratio is 6: 1)
It is prepared 2 to measure embodiment 1, and 5-dihydroxy benzenes sulfonic acid solution 10ml, stirring state slowly add solid oxidation magnesium and zinc oxide mix powder down, stirring and dissolving, until about pH=2, reaction solution is concentrated into dried, the baby pink crude product.Crude product solid chemical compound washing with acetone filters, solid in the mixing solutions of chloroform and methyl alcohol with silica gel adsorption by refining pure product.Pure product under 1.33kPa pressure, 120 ℃ of conditions dry 24 hours 2,5-dihydroxy benzenes sulfonic acid magnesium zinc composite salt (Mg: the Zn mol ratio is 6: 1) white crystalline powder.
Content: 99.5%
Ultimate analysis (2C 6H 5O 5S6/7Mg1/7Zn):
Molecular weight: 408.50
Measured value: C, 35.31%; H, 2.39%; Mg, 5.15%; S, 15.59%; Zn, 2.36%
Theoretical value: C, 35.28%; H, 2.47%; Mg, 5.10%; S, 15.70%; Zn, 2.29%
1H-NMR(600MHz，CDCl 3)：δ：5.05(4H，w)，6.61(2H，d)，6.87(2H，d)，7.23(2H，s)
IR(KBr)cm -1：3054，1974，1769，1621，1188，753，699
Embodiment 10 2, the preparation of 5-dihydroxy benzenes sulfonic acid magnesium zinc composite salt (Mg: the Zn mol ratio is 6: 1) tetrahydrate
It is prepared 2 to measure embodiment 1, and 5-dihydroxy benzenes sulfonic acid solution 10ml, stirring state slowly add solid oxidation magnesium and zinc oxide mix powder down, stirring and dissolving, until about pH=2, reaction solution is concentrated into dried, the baby pink crude product.Crude product solid chemical compound washing with acetone filters, solid in the mixing solutions of chloroform and methyl alcohol with silica gel adsorption by refining pure product.Pure product under 1.33kPa pressure, 80 ℃ of conditions dry 4 hours 2,5-dihydroxy benzenes sulfonic acid magnesium zinc composite salt tetrahydrate (Mg: the Zn mol ratio is 6: 1) white crystalline powder.
Content HPLC:99.7%
Molecular weight: 480.57
Ultimate analysis (2C 6H 5O 5S6/7Mg1/7Zn4H 2O):
Actual value C:30.01%H:3.76%S:13.37%Mg:4.36%Zn:1.92%
Theoretical value C:29.99%H:3.78%S:13.34%Mg:4.34%Zn:1.94%
1H-NMR(600MHz，CDCl 3)：δ：5.03(4H，w)，6.64(2H，d)，6.87(2H，d)，7.28(2H，s)
IR(KBr)cm -1：3056，1977，1763，1624、1185，755，703
Thermogravimetric differential thermal analysis (2C 6H 5O 5S6/7Mg1/7Zn4H 2O):
Compound is amounted to four crystal water 100 ℃～200 ℃ weightlessness 15.24%.
Embodiment 11 2, the preparation of 5-dihydroxy benzenes sulfonic acid magnesium zinc double salt (Mg: the Zn mol ratio is 9: 1)
It is prepared 2 to measure embodiment 1, and 5-dihydroxy benzenes sulfonic acid solution 10ml, stirring state slowly add solid oxidation magnesium and zinc oxide mix powder (mol ratio is 9: 1) down, stirring and dissolving, until about pH=2, reaction solution is concentrated into dried, the baby pink crude product.Crude product solid chemical compound washing with acetone filters, solid in the mixing solutions of chloroform and methyl alcohol with silica gel adsorption by refining pure product.Pure product under 1.33kPa pressure, 120 ℃ of conditions dry 24 hours 2,5-dihydroxy benzenes sulfonic acid magnesium zinc composite salt (Mg: the Zn mol ratio is 9: 1) white crystalline powder.
Content: 99.6%
Ultimate analysis (2C 6H 5O 5S9/10Mg1/10Zn):
Molecular weight: 406.75
Measured value: C, 35.38%; H, 2.53%; Mg, 5.34%; S, 15.70%; Zn, 1.59%
Theoretical value: C, 35.43%; H, 2.48%; Mg, 5.38%; S, 15.77%; Zn, 1.61%
1H-NMR(600MHz，CDCl 3)：δ：5.02(4H，w)，6.67(2H，d)，6.86(2H，d)，7.27(2H，s)
IR(KBr)cm -1：3050，1979，1763，1628，1185，757，697
Embodiment 12 2, the preparation of 5-dihydroxy benzenes sulfonic acid magnesium zinc double salt (Mg: the Zn mol ratio is 9: 1) tetrahydrate
It is prepared 2 to measure embodiment 1, and 5-dihydroxy benzenes sulfonic acid solution 10ml, stirring state slowly add solid oxidation magnesium and zinc oxide mix powder (mol ratio is 9: 1) down, stirring and dissolving, until about pH=2, reaction solution is concentrated into dried, the baby pink crude product.Crude product solid chemical compound washing with acetone filters, solid in the mixing solutions of chloroform and methyl alcohol with silica gel adsorption by refining pure product.Pure product under 1.33kPa pressure, 80 ℃ of conditions dry 4 hours 2,5-dihydroxy benzenes sulfonic acid magnesium zinc composite salt tetrahydrate (Mg: the Zn mol ratio is 9: 1) white crystalline powder.
Content: 99.5%
Ultimate analysis (2C 6H 5O 5S9/10Mg1/10Zn4H 2O):
Molecular weight: 478.81
Measured value: C, 30.24%; H, 3.85%; Mg, 4.33%; S, 13.32%; Zn, 1.42%
Theoretical value: C, 30.10%; H, 3.79%; Mg, 4.57%; S, 13.39%; Zn, 1.37%
1H-NMR(600MHz，CDCl 3)：δ：5.03(4H，w)，6.65(2H，d)，6.87(2H，d)，7.29(2H，s)
IR(KBr)cm -1：3053，1974，1766，1622，1187，756，707
Thermogravimetric differential thermal analysis (2C 6H 5O 5S9/10Mg1/10Zn4H 2O):
Compound is amounted to four crystal water 100 ℃～200 ℃ weightlessness 15.36%.
Embodiment 13 2, the preparation of 5-dihydroxy benzenes sulfonic acid magnesium zinc double salt (Mg: the Zn mol ratio is 11: 1)
It is prepared 2 to measure embodiment 1, and 5-dihydroxy benzenes sulfonic acid solution 10ml, stirring state slowly add solid oxidation magnesium and zinc oxide mix powder (mol ratio is 11: 1) down, stirring and dissolving, until about pH=2, reaction solution is concentrated into dried, the baby pink crude product.Crude product solid chemical compound washing with acetone filters, solid in the mixing solutions of chloroform and methyl alcohol with silica gel adsorption by refining pure product.Pure product under 1.33kPa pressure, 120 ℃ of conditions dry 24 hours 2,5-dihydroxy benzenes sulfonic acid magnesium zinc composite salt (Mg: the Zn mol ratio is 11: 1) white crystalline powder.
Content: 99.7%
Ultimate analysis (2C 6H 5O 5S11/12Mg1/12Zn):
Molecular weight: 406.06
Measured value: C, 35.43%; H, 2.54%; Mg, 5.47%; S, 15.75%; Zn, 1.34%
Theoretical value: C, 35.49%; H, 2.48%; Mg, 5.49%; S, 15.79%; Zn, 1.34%
1H-NMR(600MHz，CDCl 3)：δ：5.09(4H，w)，6.67(2H，d)，6.86(2H，d)，7.28(2H，s)
IR(KBr)cm -1：3055，1974，1768，1623，1187，754，698
Embodiment 14 2, the preparation of 5-dihydroxy benzenes sulfonic acid magnesium zinc double salt (Mg: the Zn mol ratio is 11: 1) tetrahydrate
It is prepared 2 to measure embodiment 1, and 5-dihydroxy benzenes sulfonic acid solution 10ml, stirring state slowly add solid oxidation magnesium and zinc oxide mix powder (mol ratio is 11: 1) down, stirring and dissolving, until about pH=2, reaction solution is concentrated into dried, the baby pink crude product.Crude product solid chemical compound washing with acetone filters, solid in the mixing solutions of chloroform and methyl alcohol with silica gel adsorption by refining pure product.Pure product under 1.33kPa pressure, 80 ℃ of conditions dry 4 hours 2,5-dihydroxy benzenes sulfonic acid magnesium zinc composite salt tetrahydrate (Mg: the Zn mol ratio is 11: 1) white crystalline powder.
Content: 99.5%
Ultimate analysis (2C 6H 5O 5S11/12Mg1/12Zn4H 2O):
Molecular weight: 478.13
Measured value: C, 30.28%; H, 3.59%; Mg, 4.57%; S, 13.36%; Zn, 1.27%
Theoretical value: C, 30.14%; H, 3.79%; Mg, 4.66%; S, 13.14%; Zn, 1.14%
1H-NMR(600MHz，CDCl 3)：δ：5.08(4H，w)，6.64(2H，d)，6.87(2H，d)，7.31(2H，s)
IR(KBr)cm -1：3057，1975，1767，1625，1197，754，702
Thermogravimetric differential thermal analysis (2C 6H 5O 5S11/12Mg1/12Zn4H 2O):
Compound is amounted to four crystal water 100 ℃～200 ℃ weightlessness 15.09%.
Embodiment 15 2, the preparation of 5-dihydroxy benzenes sulfonic acid magnesium zinc double salt (Mg: the Zn mol ratio is 19: 1)
It is prepared 2 to measure embodiment 1, and 5-dihydroxy benzenes sulfonic acid solution 10ml, stirring state slowly add solid oxidation magnesium and zinc oxide mix powder (mol ratio is 19: 1) down, stirring and dissolving, until about pH=2, reaction solution is concentrated into dried, the baby pink crude product.Crude product solid chemical compound washing with acetone filters, solid in the mixing solutions of chloroform and methyl alcohol with silica gel adsorption by refining pure product.Pure product under 1.33kPa pressure, 120 ℃ of conditions dry 24 hours 2,5-dihydroxy benzenes sulfonic acid magnesium zinc composite salt (Mg: the Zn mol ratio is 19: 1) white crystalline powder.
Content: 99.1%
Ultimate analysis (2C 6H 5O 5S19/20Mg1/20Zn):
Molecular weight: 404.69
Measured value: C, 35.63%; H, 2.47%; Mg, 5.74%; S, 15.81%; Zn, 0.83%
Theoretical value: C, 35.61%; H, 2.49%; Mg, 5.71%; S, 15.85%; Zn, 0.81%
1H-NMR(600MHz，CDCl 3)：δ：5.06(4H，w)，6.64(2H，d)，6.85(2H，d)，7.22(2H，s)
IR(KBr)cm -1：3055，1973，1767，1628，1185，751，698
Embodiment 16 2, the preparation of 5-dihydroxy benzenes sulfonic acid magnesium zinc double salt (Mg: the Zn mol ratio is 19: 1) tetrahydrate
It is prepared 2 to measure embodiment 1, and 5-dihydroxy benzenes sulfonic acid solution 10ml, stirring state slowly add solid oxidation magnesium and zinc oxide mix powder (mol ratio is 19: 1) down, stirring and dissolving, until about pH=2, reaction solution is concentrated into dried, the baby pink crude product.Crude product solid chemical compound washing with acetone filters, solid in the mixing solutions of chloroform and methyl alcohol with silica gel adsorption by refining pure product.Pure product under 1.33kPa pressure, 80 ℃ of conditions dry 4 hours 2,5-dihydroxy benzenes sulfonic acid magnesium zinc composite salt tetrahydrate (Mg: the Zn mol ratio is 19: 1) white crystalline powder.
Content: 99.6%
Ultimate analysis (2C 6H 5O 5S19/20Mg1/20Zn4H 2O):
Molecular weight: 476.75
Measured value: C, 30.26%; H, 3.80%; Mg, 4.86%; S, 13.40%; Zn, 0.71%
Theoretical value: C, 30.23%; H, 3.81%; Mg, 4.84%; S, 13.45%; Zn, 0.69%
1H-NMR(600MHz，CDCl 3)：δ：5.05(4H，w)，6.67(2H，d)，6.85(2H，d)，7.32(2H，s)
IR(KBr)cm -1：3056，1974，1766，1622，1192，752，701
Thermogravimetric differential thermal analysis (2C 6H 5O 5S19/20Mg1/20Zn4H 2O):
Compound is amounted to four crystal water 100 ℃～200 ℃ weightlessness 15.13%.
Embodiment 17 2, the preparation of 5-dihydroxy benzenes sulfonic acid magnesium zinc double salt (Mg: the Zn mol ratio is 29: 1)
It is prepared 2 to measure embodiment 1, and 5-dihydroxy benzenes sulfonic acid solution 10ml, stirring state slowly add solid oxidation magnesium and zinc oxide mix powder (mol ratio is 29: 1) down, stirring and dissolving, until about pH=2, reaction solution is concentrated into dried, the baby pink crude product.Crude product solid chemical compound washing with acetone filters, solid in the mixing solutions of chloroform and methyl alcohol with silica gel adsorption by refining pure product.Pure product under 1.33kPa pressure, 120 ℃ of conditions dry 24 hours 2,5-dihydroxy benzenes sulfonic acid magnesium zinc composite salt (Mg: the Zn mol ratio is 29: 1) white crystalline powder.
Content: 98.5%
Ultimate analysis (2C 6H 5O 5S29/30Mg1/30Zn):
Molecular weight: 404.01
Measured value: C, 35.63%; H, 2.55%; Mg, 5.79%; S, 15.83%; Zn, 0.55%
Theoretical value: C, 35.67%; H, 2.49%; Mg, 5.82%; S, 15.87%; Zn, 0.54%
1H-NMR(600MHz，CDCl 3)：δ：5.03(4H，w)，6.65(2H，d)，6.84(2H，d)，7.22(2H，s)
IR(KBr)cm -1：3055，1971，1767，1624，1187，751，700
Embodiment 18 2, the preparation of 5-dihydroxy benzenes sulfonic acid magnesium zinc double salt (Mg: the Zn mol ratio is 29: 1) tetrahydrate
It is prepared 2 to measure embodiment 1, and 5-dihydroxy benzenes sulfonic acid solution 10ml, stirring state slowly add solid oxidation magnesium and zinc oxide mix powder (mol ratio is 29: 1) down, stirring and dissolving, until about pH=2, reaction solution is concentrated into dried, the baby pink crude product.Crude product solid chemical compound washing with acetone filters, solid in the mixing solutions of chloroform and methyl alcohol with silica gel adsorption by refining pure product.Pure product under 1.33kPa pressure, 80 ℃ of conditions dry 4 hours 2,5-dihydroxy benzenes sulfonic acid magnesium zinc composite salt tetrahydrate (Mg: the Zn mol ratio is 29: 1) white crystalline powder.
Content: 99.7%
Ultimate analysis (2C 6H 5O 5S29/30Mg1/30Zn4H 2O):
Molecular weight: 476.07
Measured value: C, 30.18%; H, 3.80%; Mg, 4.96%; S, 13.45%; Zn, 0.48%
Theoretical value: C, 30.27%; H, 3.81%; Mg, 4.94%; S, 13.47%; Zn, 0.46%
1H-NMR(600MHz，CDCl 3)：δ：5.06(4H，w)，6.62(2H，d)，6.88(2H，d)，7.23(2H，s)
IR(KBr)cm -1：3056，1975，1765，1623，1184，755，706
Thermogravimetric differential thermal analysis (2C 6H 5O 5S29/30Mg1/30Zn4H 2O):
Compound is amounted to four crystal water 100 ℃～200 ℃ weightlessness 15.15%.
Embodiment 19 2, the preparation of 5-dihydroxy benzenes sulfonic acid calcium zinc double salt (Ca: the Zn mol ratio is 2: 1)
It is prepared 2 to measure embodiment 1, and 5-dihydroxy benzenes sulfonic acid solution 10ml, stirring state slowly add solid oxidation calcium and oxide powder and zinc (mol ratio is 2: 1) down, stirring and dissolving until about pH=2, is concentrated into reaction solution dried, get baby pink 2,5-dihydroxy benzenes sulfonic acid calcium zinc double salt crude product.Crude product solid chemical compound washing with acetone filters, solid in the mixing solutions of chloroform and methyl alcohol with silica gel adsorption by refining pure product.Pure product under 1.33kPa pressure, 120 ℃ of conditions dry 24 hours 2,5-dihydroxy benzenes sulfonic acid calcium zinc composite salt white crystalline powder.
Content: 99.4%
Ultimate analysis (2C 6H 5O 5S2/3Ca1/3Zn):
Molecular weight: 426.83
Measured value: C, 33.68%; H, 2.41%; Ca, 6.28%; S, 15.08%; Zn, 5.10%
Theoretical value: C, 33.77%; H, 2.36%; Ca, 6.26%; S, 15.02%; Zn, 5.11%
1H-NMR(600MHz，CDCl 3)：δ：5.11(4H，w)，6.63(2H，d)，6.82(2H，d)，7.37(2H，s)
IR(KBr)cm -1：3051，1972，1764，1623，1186，757，700
Embodiment 20 2, the preparation of 5-dihydroxy benzenes sulfonic acid calcium zinc double salt (Ca: the Zn mol ratio is 2: 1) hydrate
It is prepared 2 to measure embodiment 1, and 5-dihydroxy benzenes sulfonic acid solution 10ml, stirring state slowly add solid oxidation calcium and oxide powder and zinc (mol ratio is 2: 1) down, stirring and dissolving until about pH=2, is concentrated into reaction solution dried, get baby pink 2,5-dihydroxy benzenes sulfonic acid calcium zinc double salt crude product.Crude product solid chemical compound washing with acetone filters, solid in the mixing solutions of chloroform and methyl alcohol with silica gel adsorption by refining pure product.Pure product under 1.33kPa pressure, 80 ℃ of conditions dry 4 hours 2,5-dihydroxy benzenes sulfonic acid calcium zinc composite salt hydrate white crystalline powder.
Content: 99.1%
Ultimate analysis (2C 6H 5O 5S2/3Ca1/3Zn2H 2O):
Molecular weight: 462.87
Measured value: C, 31.12%; H, 3.02%; Ca, 5.79%; S, 13.89%; Zn, 4.73%
Theoretical value: C, 31.14%; H, 3.05%; Ca, 5.77%; S, 13.85%; Zn, 4.71%
1H-NMR(600MHz，CDCl 3)：δ：5.02(4H，w)，6.61(2H，d)，6.81(2H，d)，7.27(2H，s)
IR(KBr)cm -1：3049，1970，1761，1629，1188，754，704
Thermogravimetric differential thermal analysis (2C 6H 5O 5S2/3Ca1/3Zn2H 2O):
Compound is amounted to two crystal water 100 ℃～200 ℃ weightlessness 7.81%.
Embodiment 21 2, the preparation of 5-dihydroxy benzenes sulfonic acid calcium zinc double salt (Ca: the Zn mol ratio is 4: 1)
It is prepared 2 to measure embodiment 1, and 5-dihydroxy benzenes sulfonic acid solution 10ml, stirring state slowly add solid oxidation calcium and oxide powder and zinc (mol ratio is 4: 1) down, stirring and dissolving until about pH=2, is concentrated into reaction solution dried, get baby pink 2,5-dihydroxy benzenes sulfonic acid calcium zinc double salt crude product.Crude product solid chemical compound washing with acetone filters, solid in the mixing solutions of chloroform and methyl alcohol with silica gel adsorption by refining pure product.Pure product under 1.33kPa pressure, 120 ℃ of conditions dry 24 hours 2,5-dihydroxy benzenes sulfonic acid calcium zinc composite salt white crystalline powder.
Content: 99.4%
Ultimate analysis (2C 6H 5O 5S4/5Ca1/5Zn):
Molecular weight: 423.48
Measured value: C, 34.10%; H, 2.41%; Ca, 7.59%; S, 15.12%; Zn, 3.08%
Theoretical value: C, 34.03%; H, 2.38%; Ca, 7.57%; S, 15.14%; Zn, 3.09%
1H-NMR(600MHz，CDCl 3)：δ：5.11(4H，w)，6.63(2H，d)，6.82(2H，d)，7.37(2H，s)
IR(KBr)cm -1：3051，1972，1764，1623，1186，757，700
Embodiment 22 2, the preparation of 5-dihydroxy benzenes sulfonic acid calcium zinc double salt (Ca: the Zn mol ratio is 4: 1) hydrate
It is prepared 2 to measure embodiment 1, and 5-dihydroxy benzenes sulfonic acid solution 10ml, stirring state slowly add solid oxidation calcium and oxide powder and zinc (mol ratio is 4: 1) down, stirring and dissolving until about pH=2, is concentrated into reaction solution dried, get baby pink 2,5-dihydroxy benzenes sulfonic acid calcium zinc double salt crude product.Crude product solid chemical compound washing with acetone filters, solid in the mixing solutions of chloroform and methyl alcohol with silica gel adsorption by refining pure product.Pure product under 1.33kPa pressure, 80 ℃ of conditions dry 4 hours 2,5-dihydroxy benzenes sulfonic acid calcium zinc composite salt hydrate white crystalline powder.
Content: 99.1%
Ultimate analysis (2C 6H 5O 5S4/5Ca1/5Zn8/5H 2O):
Molecular weight: 452.30
Measured value: C, 31.79%; H, 2.91%; Ca, 7.10%; S, 14.23%; Zn, 2.92%
Theoretical value: C, 31.87%; H, 2.94%; Ca, 7.09%; S, 14.18%; Zn, 2.89%
1H-NMR(600MHz，CDCl 3)：δ：5.02(4H，w)，6.61(2H，d)，6.81(2H，d)，7.27(2H，s)
IR(KBr)cm -1：3049，1970，1761，1629，1188，754，704
Thermogravimetric differential thermal analysis (2C 6H 5O 5S4/5Ca1/5Zn8/5H 2O):
Compound is amounted to 8/5 crystal water 100 ℃～200 ℃ weightlessness 6.38%.
Embodiment 23 2, the preparation of 5-dihydroxy benzenes sulfonic acid calcium zinc double salt (Ca: the Zn mol ratio is 5: 1)
It is prepared 2 to measure embodiment 1, and 5-dihydroxy benzenes sulfonic acid solution 10ml, stirring state slowly add solid oxidation calcium and oxide powder and zinc (mol ratio is 5: 1) down, stirring and dissolving until about pH=2, is concentrated into reaction solution dried, get baby pink 2,5-dihydroxy benzenes sulfonic acid calcium zinc double salt crude product.Product solid chemical compound washing with acetone mutually filters, solid in the mixing solutions of chloroform and methyl alcohol with silica gel adsorption by refining pure product.Pure product under 1.33kPa pressure, 120 ℃ of conditions dry 24 hours 2,5-dihydroxy benzenes sulfonic acid calcium zinc composite salt white crystalline powder.
Content: 99.0%
Ultimate analysis (2C 6H 5O 5S5/6Ca1/6Zn):
Molecular weight: 422.63
Measured value: C, 34.05%; H, 2.45%; Ca, 7.91%; S, 15.14%; Zn, 2.59%
Theoretical value: C, 34.10%; H, 2.38%; Ca, 7.90%; S, 15.17%; Zn, 2.58%
1H-NMR(600MHz，CDCl 3)：δ：5.07(4H，w)，6.62(2H，d)，6.84(2H，d)，7.33(2H，s)
IR(KBr)cm -1：3054，1979，1767，1625，1187，756，702
Embodiment 24 2, the preparation of 5-dihydroxy benzenes sulfonic acid calcium zinc double salt (Ca: the Zn mol ratio is 5: 1) hydrate
It is prepared 2 to measure embodiment 1, and 5-dihydroxy benzenes sulfonic acid solution 10ml, stirring state slowly add solid oxidation calcium and oxide powder and zinc (mol ratio is 5: 1) down, stirring and dissolving until about pH=2, is concentrated into reaction solution dried, get baby pink 2,5-dihydroxy benzenes sulfonic acid calcium zinc double salt crude product.Crude product solid chemical compound washing with acetone filters, solid in the mixing solutions of chloroform and methyl alcohol with silica gel adsorption by refining pure product.Pure product under 1.33kPa pressure, 80 ℃ of conditions dry 4 hours 2,5-dihydroxy benzenes sulfonic acid calcium zinc composite salt hydrate white crystalline powder.
Content: 99.5%
Ultimate analysis (2C 6H 5O 5S5/6Ca1/6Zn9/6H 2O):
Molecular weight: 449.65
Measured value: C, 32.01%; H, 2.87%; Ca, 7.46%; S, 14.25%; Zn, 2.46%
Theoretical value: C, 32.05%; H, 2.91%; Ca, 7.43%; S, 14.26%; Zn, 2.42%
1H-NMR(600MHz，CDCl 3)：δ：5.06(4H，w)，6.64(2H，d)，6.87(2H，d)，7.25(2H，s)
IR(KBr)cm -1：3058，1975，1767，1634，1188，754，705
Thermogravimetric differential thermal analysis (2C 6H 5O 5S5/6Ca1/6Zn9/6H 2O):
Compound is amounted to 9/6 crystal water 100 ℃～200 ℃ weightlessness 6.04%.
Embodiment 25 2, the preparation of 5-dihydroxy benzenes sulfonic acid calcium zinc double salt (Ca: the Zn mol ratio is 6: 1)
It is prepared 2 to measure embodiment 1, and 5-dihydroxy benzenes sulfonic acid solution 10ml, stirring state slowly add solid oxidation calcium and oxide powder and zinc (mol ratio is 6: 1) down, stirring and dissolving until about pH=2, is concentrated into reaction solution dried, get baby pink 2,5-dihydroxy benzenes sulfonic acid calcium zinc double salt crude product.Crude product solid chemical compound washing with acetone filters, solid in the mixing solutions of chloroform and methyl alcohol with silica gel adsorption by refining pure product.Pure product under 1.33kPa pressure, 120 ℃ of conditions dry 4 hours 2,5-dihydroxy benzenes sulfonic acid calcium zinc composite salt white crystalline powder.
Content: 98.9%
Ultimate analysis (2C 6H 5O 5S6/7Ca1/7Zn):
Molecular weight: 422.03
Measured value: C, 33.98%; H, 2.41%; Ca, 8.20%; S, 15.18%; Zn, 2.23%
Theoretical value: C, 34.15%; H, 2.39%; Ca, 8.14%; S, 15.20%; Zn, 2.21%
1H-NMR(600MHz，CDCl 3)：δ：5.07(4H，w)，6.67(2H，d)，6.83(2H，d)，7.37(2H，s)
IR(KBr)cm -1：3054，1977，1768，1624，1185，754，705
Embodiment 26 2, the preparation of 5-dihydroxy benzenes sulfonic acid calcium zinc double salt (Ca: the Zn mol ratio is 6: 1) hydrate
It is prepared 2 to measure embodiment 1, and 5-dihydroxy benzenes sulfonic acid solution 10ml, stirring state slowly add solid oxidation calcium and oxide powder and zinc (mol ratio is 6: 1) down, stirring and dissolving until about pH=2, is concentrated into reaction solution dried, get baby pink 2,5-dihydroxy benzenes sulfonic acid calcium zinc double salt crude product.Crude product solid chemical compound washing with acetone filters, solid in the mixing solutions of chloroform and methyl alcohol with silica gel adsorption by refining pure product.Pure product under 1.33kPa pressure, 80 ℃ of conditions dry 4 hours 2,5-dihydroxy benzenes sulfonic acid calcium zinc composite salt hydrate white crystalline powder.
Content: 99.4%
Ultimate analysis (2C 6H 5O 5S6/7Ca1/7Zn10/7H 2O):
Molecular weight: 447.76
Measured value: C, 32.01%; H, 2.88%; Ca, 7.45%; S, 14.28%; Zn, 2.46%
Theoretical value: C, 32.05%; H, 2.91%; Ca, 7.43%; S, 14.26%; Zn, 2.42%
1H-NMR(600MHz，CDCl 3)：δ：5.05(4H，w)，6.63(2H，d)，6.86(2H，d)，7.33(2H，s)
IR(KBr)cm -1：3054，1972，1763，1636，1188，759，704
Thermogravimetric differential thermal analysis (2C 6H 5O 5S6/7Ca1/7Zn10/7H 2O):
Compound is amounted to 10/7 crystal water 100 ℃～200 ℃ weightlessness 5.76%.
Embodiment 27 2, the preparation of 5-dihydroxy benzenes sulfonic acid calcium zinc double salt (Ca: the Zn mol ratio is 9: 1)
It is prepared 2 to measure embodiment 1, and 5-dihydroxy benzenes sulfonic acid solution 10ml, stirring state slowly add solid oxidation calcium and oxide powder and zinc (mol ratio is 9: 1) down, stirring and dissolving until about pH=2, is concentrated into reaction solution dried, get baby pink 2,5-dihydroxy benzenes sulfonic acid calcium zinc double salt crude product.Crude product solid chemical compound washing with acetone filters, solid in the mixing solutions of chloroform and methyl alcohol with silica gel adsorption by refining pure product.Pure product under 1.33kPa pressure, 120 ℃ of conditions dry 24 hours 2,5-dihydroxy benzenes sulfonic acid calcium zinc composite salt white crystalline powder
Content: 99.8%
Ultimate analysis (2C 6H 5O 5S9/10Ca1/10Zn):
Molecular weight: 420.94
Measured value: C, 34.19%; H, 2.49%; Ca, 8.53%; S, 15.20%; Zn, 1.51%
Theoretical value: C, 34.24%; H, 2.39%; Ca, 8.57%; S, 15.23%; Zn, 1.55%
1H-NMR(600MHz，CDCl 3)：δ：5.06(4H，w)，6.61(2H，d)，6.85(2H，d)，7.32(2H，s)
IR(KBr)cm -1：3056，1974，1762，1621，1187，755，705
Embodiment 28 2, the preparation of 5-dihydroxy benzenes sulfonic acid calcium zinc double salt (Ca: the Zn mol ratio is 9: 1) hydrate
It is prepared 2 to measure embodiment 1, and 5-dihydroxy benzenes sulfonic acid solution 10ml, stirring state slowly add solid oxidation calcium and oxide powder and zinc (mol ratio is 9: 1) down, stirring and dissolving until about pH=2, is concentrated into reaction solution dried, get baby pink 2,5-dihydroxy benzenes sulfonic acid calcium zinc double salt crude product.Crude product solid chemical compound washing with acetone filters, solid in the mixing solutions of chloroform and methyl alcohol with silica gel adsorption by refining pure product.Pure product under 1.33kPa pressure, 80 ℃ of conditions dry 4 hours 2,5-dihydroxy benzenes sulfonic acid calcium zinc composite salt hydrate white crystalline powder
Content: 99.3%
Ultimate analysis (2C 6H 5O 5S9/10Ca1/10Zn13/10H 2O):
Molecular weight: 444.36
Measured value: C, 32.41%; H, 2.81%; Ca, 8.14%; S, 14.45%; Zn, 1.49%
Theoretical value: C, 32.43%; H, 2.86%; Ca, 8.12%; S, 14.43%; Zn, 1.47%
1H-NMR(600MHz，CDCl 3)：δ：5.06(4H，w)，6.64(2H，d)，6.85(2H，d)，7.22(2H，s)
IR(KBr)cm -1：3053，1971，1762，1624，1185，751，705
Thermogravimetric differential thermal analysis (2C 6H 5O 5S9/10Ca1/10Zn13/10H 2O):
Compound is amounted to 13/10 crystal water 100 ℃～200 ℃ weightlessness 5.31%.
Embodiment 29 2, the preparation of 5-dihydroxy benzenes sulfonic acid calcium zinc double salt (Ca: the Zn mol ratio is 11: 1)
It is prepared 2 to measure embodiment 1, and 5-dihydroxy benzenes sulfonic acid solution 10ml, stirring state slowly add solid oxidation calcium and oxide powder and zinc (mol ratio is 11: 1) down, stirring and dissolving until about pH=2, is concentrated into reaction solution dried, get baby pink 2,5-dihydroxy benzenes sulfonic acid calcium zinc double salt crude product.Crude product solid chemical compound washing with acetone filters, solid in the mixing solutions of chloroform and methyl alcohol with silica gel adsorption by refining pure product.Pure product under 1.33kPa pressure, 120 ℃ of conditions dry 24 hours 2,5-dihydroxy benzenes sulfonic acid calcium zinc composite salt white crystalline powder
Content: 99.5%
Ultimate analysis (2C 6H 5O 5S11/12Ca1/12Zn):
Molecular weight: 420.52
Measured value: C, 34.24%; H, 2.47%; Ca, 8.72%; S, 15.22%; Zn, 1.33%
Theoretical value: C, 34.27%; H, 2.40%; Ca, 8.74%; S, 15.25%; Zn, 1.30%
1H-NMR(600MHz，CDCl 3)：δ：5.05(4H，w)，6.64(2H，d)，6.85(2H，d)，7.31(2H，s)
IR(KBr)cm -1：3055，1976，1762，1627，1184，755，703
Embodiment 30 2, the preparation of 5-dihydroxy benzenes sulfonic acid calcium zinc double salt (Ca: the Zn mol ratio is 11: 1) hydrate
It is prepared 2 to measure embodiment 1, and 5-dihydroxy benzenes sulfonic acid solution 10ml, stirring state slowly add solid oxidation calcium and oxide powder and zinc (mol ratio is 11: 1) down, stirring and dissolving until about pH=2, is concentrated into reaction solution dried, get baby pink 2,5-dihydroxy benzenes sulfonic acid calcium zinc double salt crude product.Crude product solid chemical compound washing with acetone filters, solid in the mixing solutions of chloroform and methyl alcohol with silica gel adsorption by refining pure product.Pure product under 1.33kPa pressure, 80 ℃ of conditions dry 4 hours 2,5-dihydroxy benzenes sulfonic acid calcium zinc composite salt hydrate white crystalline powder.
Content: 99.3%
Ultimate analysis (2C 6H 5O 5S11/12Ca1/12Zn15/12H 2O):
Molecular weight: 443.04
Measured value: C, 32.51%; H, 2.80%; Ca, 8.31%; S, 14.49%; Zn, 1.25%
Theoretical value: C, 32.53%; H, 2.84%; Ca, 8.29%; S, 14.48%; Zn, 1.23%C, 32.53; H, 2.84; Ca, 8.29; O, 40.63; S, 14.48; Zn, 1.23
1H-NMR(600MHz，CDCl 3)：δ：5.02(4H，w)，6.65(2H，d)，6.84(2H，d)，7.28(2H，s)
IR(KBr)cm -1：3056，1978，1764，1636，1184，753，706
Thermogravimetric differential thermal analysis (2C 6H 5O 5S11/12Ca1/12Zn15/12H 2O):
Compound is amounted to 15/12 crystal water 100 ℃～200 ℃ weightlessness 5.11%.
Embodiment 31 2, the preparation of 5-dihydroxy benzenes sulfonic acid calcium zinc double salt (Ca: the Zn mol ratio is 19: 1)
It is prepared 2 to measure embodiment 1, and 5-dihydroxy benzenes sulfonic acid solution 10ml, stirring state slowly add solid oxidation calcium and oxide powder and zinc (mol ratio is 19: 1) down, stirring and dissolving until about pH=2, is concentrated into reaction solution dried, get baby pink 2,5-dihydroxy benzenes sulfonic acid calcium zinc double salt crude product.Crude product solid chemical compound washing with acetone filters, solid in the mixing solutions of chloroform and methyl alcohol with silica gel adsorption by refining pure product.Pure product under 1.33kPa pressure, 120 ℃ of conditions dry 24 hours 2,5-dihydroxy benzenes sulfonic acid calcium zinc composite salt white crystalline powder.
Content: 99.4%
Ultimate analysis (2C 6H 5O 5S19/20Ca1/20Zn):
Molecular weight: 419.68
Measured value: C, 34.36%; H, 2.43%; Ca, 9.10%; S, 15.23%; Zn, 0.79%
Theoretical value: C, 34.34%; H, 2.40%; Ca, 9.07%; S, 15.28%; Zn, 0.78%
1H-NMR(600MHz，CDCl 3)：δ：5.06(4H，w)，6.65(2H，d)，6.84(2H，d)，7.36(2H，s)
IR(KBr)cm -1：3057，1975，1764，1625，1188，754，701
Embodiment 322, the preparation of 5-dihydroxy benzenes sulfonic acid calcium zinc double salt (Ca: the Zn mol ratio is 19: 1) hydrate
It is prepared 2 to measure embodiment 1, and 5-dihydroxy benzenes sulfonic acid solution 10ml, stirring state slowly add solid oxidation calcium and oxide powder and zinc (mol ratio is 19: 1) down, stirring and dissolving until about pH=2, is concentrated into reaction solution dried, get baby pink 2,5-dihydroxy benzenes sulfonic acid calcium zinc double salt crude product.Crude product solid chemical compound washing with acetone filters, solid in the mixing solutions of chloroform and methyl alcohol with silica gel adsorption by refining pure product.Pure product under 1.33kPa pressure, 80 ℃ of conditions dry 4 hours 2,5-dihydroxy benzenes sulfonic acid calcium zinc composite salt hydrate white crystalline powder.
Content: 99.6%
Ultimate analysis (2C 6H 5O 5S19/20Ca1/20Zn23/20H 2O):
Molecular weight: 440.40
Measured value: C, 32.69%; H, 2.78%; Ca, 8.68%; S, 14.58%; Zn, 0.75%
Theoretical value: C, 32.73%; H, 2.82%; Ca, 8.65%; S, 14.56%; Zn, 0.74%
1H-NMR(600MHz，CDCl 3)：δ：5.06(4H，w)，6.64(2H，d)，6.82(2H，d)，7.29(2H，s)
IR(KBr)cm -1：3053，1972，1765，1632，1185，758，701
Thermogravimetric differential thermal analysis (2C 6H 5O 5S19/20Ca1/20Zn23/20H 2O):
Compound is amounted to 23/20 crystal water 100 ℃～200 ℃ weightlessness 4.72%.
Embodiment 33 2, the preparation of 5-dihydroxy benzenes sulfonic acid calcium zinc double salt (Ca: the Zn mol ratio is 29: 1)
It is prepared 2 to measure embodiment 1, and 5-dihydroxy benzenes sulfonic acid solution 10ml, stirring state slowly add solid oxidation calcium and oxide powder and zinc (mol ratio is 29: 1) down, stirring and dissolving until about pH=2, is concentrated into reaction solution dried, get baby pink 2,5-dihydroxy benzenes sulfonic acid calcium zinc double salt crude product.Crude product solid chemical compound washing with acetone filters, solid in the mixing solutions of chloroform and methyl alcohol with silica gel adsorption by refining pure product.Pure product under 1.33kPa pressure, 120 ℃ of conditions dry 24 hours 2,5-dihydroxy benzenes sulfonic acid calcium zinc composite salt white crystalline powder.
Content: 99.8%
Ultimate analysis (2C 6H 5O 5S29/30Ca1/30Zn):
Molecular weight: 419.25
Measured value: C, 34.35%; H, 2.49%; Ca, 9.21%; S, 15.28%; Zn, 0.50%
Theoretical value: C, 34.38%; H, 2.40%; Ca, 9.24%; S, 15.30%; Zn, 0.52%
1H-NMR(600MHz，CDCl 3)：δ：5.09(4H，w)，6.61(2H，d)，6.85(2H，d)，7.34(2H，s)
IR(KBr)cm -1：3053，1975，1766，1624，1187，755，702
Embodiment 34 2, the preparation of 5-dihydroxy benzenes sulfonic acid calcium zinc double salt (Ca: the Zn mol ratio is 29: 1) hydrate
It is prepared 2 to measure embodiment 1, and 5-dihydroxy benzenes sulfonic acid solution 10ml, stirring state slowly add solid oxidation calcium and oxide powder and zinc (mol ratio is 29: 1) down, stirring and dissolving until about pH=2, is concentrated into reaction solution dried, get baby pink 2,5-dihydroxy benzenes sulfonic acid calcium zinc double salt crude product.Crude product solid chemical compound washing with acetone filters, solid in the mixing solutions of chloroform and methyl alcohol with silica gel adsorption by refining pure product.Pure product under 1.33kPa pressure, 80 ℃ of conditions dry 4 hours 2,5-dihydroxy benzenes sulfonic acid calcium zinc composite salt hydrate white crystalline powder.
Content: 99.7%.
Ultimate analysis (2C 6H 5O 5S29/30Ca1/30Zn33/30H 2O):
Molecular weight: 439.07
Measured value: C, 32.85%; H, 2.82%; Ca, 8.81%; S, 14.64%; Zn, 0.49%
Theoretical value: C, 32.83%; H, 2.80%; Ca, 8.82%; S, 14.61%; Zn, 0.50%
1H-NMR(600MHz，CDCl 3)：δ：5.06(4H，w)，6.63(2H，d)，6.84(2H，d)，7.29(2H，s)
IR(KBr)cm -1：3045，1966，1757，1628，1185，754，701
Thermogravimetric differential thermal analysis (2C 6H 5O 5S29/30Ca1/30Zn33/30H 2O):
Compound is amounted to 33/30 crystal water 100 ℃～200 ℃ weightlessness 4.53%.
Embodiment 35 2, the preparation of 5-dihydroxy benzenes sulfonic acid calcium magnesium double salt (Ca: the Mg mol ratio is 2: 1)
It is prepared 2 to measure embodiment 1, and 5-dihydroxy benzenes sulfonic acid solution 10ml, stirring state slowly add solid oxidation calcium and magnesia powder (mol ratio is 2: 1) down, stirring and dissolving until about pH=2, is concentrated into reaction solution dried, get 2,5-dihydroxy benzenes sulfonic acid calcium magnesium double salt crude product.Crude product solid chemical compound washing with acetone filters, solid in the mixing solutions of chloroform and methyl alcohol with silica gel adsorption by refining pure product.Pure product under 1.33kPa pressure, 120 ℃ of conditions dry 24 hours 2,5-dihydroxy benzenes sulfonic acid calcium magnesium double salt (Ca: the Mg mol ratio is 2: 1) white crystalline powder.
Content: 98.7%
Ultimate analysis (2C 6H 5O 5S2/3Ca1/3Mg):
Molecular weight: 413.17
Measured value: C, 34.81%; H, 2.41%; Ca, 6.49%; Mg, 1.94%; S, 15.53%
Theoretical value: C, 34.89%; H, 2.44%; Ca, 6.47%; Mg, 1.96%; S, 15.52%
1H-NMR(600MHz，CDCl 3)：δ：5.05(4H，w)，6.64(2H，d)，6.85(2H，d)，7.26(2H，s)
IR(KBr)cm -1：3051，1974，1765，1625，1185，755，703
Embodiment 36 2, the preparation of 5-dihydroxy benzenes sulfonic acid calcium magnesium double salt (Ca: the Mg mol ratio is 2: 1) hydrate
It is prepared 2 to measure embodiment 1, and 5-dihydroxy benzenes sulfonic acid solution 10ml, stirring state slowly add solid oxidation calcium and magnesia powder (mol ratio is 1: 1) down, stirring and dissolving until about pH=2, is concentrated into reaction solution dried, get 2,5-dihydroxy benzenes sulfonic acid calcium magnesium double salt crude product.Crude product solid chemical compound washing with acetone filters, solid in the mixing solutions of chloroform and methyl alcohol with silica gel adsorption by refining pure product.Pure product under 1.33kPa pressure, 80 ℃ of conditions dry 4 hours 2,5-dihydroxy benzenes sulfonic acid calcium magnesium double salt (Ca: the Mg mol ratio is 1: 1) hydrate white crystalline powder.
Content: be measured as 99.8% through HPLC.
Ultimate analysis (2C 6H 5O 5S2/3Ca1/3Mg2H 2O):
Molecular weight: 449.17
Measured value: C, 32.10%; H, 3.12%; Ca, 5.94%; Mg, 1.81%; S, 13.31%
Theoretical value: C, 32.09%; H, 3.14%; Ca, 5.95%; Mg, 1.80%; S, 14.28%
1H-NMR(600MHz，CDCl 3)：δ：5.06(4H，w)，6.67(2H，d)，6.86(2H，d)，7.27(2H，s)
IR(KBr)cm -1：3052，1977，1769，1629，1186，757，706
Thermogravimetric differential thermal analysis (2C 6H 5O 5S2/3Ca1/3Mg2H 2O):
Compound is amounted to two crystal water 100 ℃～200 ℃ weightlessness 2.68%.
Represent 2 with compd A among following examples 34-36,5-dihydroxy benzenes sulfonic acid magnesium zinc double salt (Mg: the Zn mol ratio is 4: 1), compd B represents 2,5-dihydroxy benzenes sulfonic acid magnesium zinc double salt (Mg: the Zn mol ratio is 5: 1), Compound C represents 2,5-dihydroxy benzenes sulfonic acid magnesium zinc double salt (Mg: the Zn mol ratio is 6: 1), Compound D represents 2,5-dihydroxy benzenes sulfonic acid magnesium zinc double salt (Mg: the Zn mol ratio is 11: 1); Compd E represents 2,5-dihydroxy benzenes sulfonic acid calcium zinc double salt (Ca: the Zn mol ratio is 6: 1), and compound F 17-hydroxy-corticosterone represents 2,5-dihydroxy benzenes sulfonic acid calcium magnesium double salt (Ca: the Mg mol ratio is 1: 1).
The preparation of embodiment 37 phenolsulfonic acid composite salt of the present invention or its hydrate tablet
1, prescription:
Prescription 1
Compd A or compd A tetrahydrate 235g (in anhydrous compound)
Microcrystalline Cellulose 80g
Pregelatinized Starch 80g
The 2%HPMC aqueous solution is an amount of
Magnesium Stearate 3g
Prepare 1000 altogether
Prescription 2
Compd B or compd B tetrahydrate 235g (in anhydrous compound)
Pregelatinized Starch 80g
Microcrystalline Cellulose 80g
The 2%HPMC aqueous solution is an amount of
Magnesium Stearate 3g
Prepare 1000 altogether
Prescription 3
Compound C or Compound C tetrahydrate 234g (in anhydrous compound)
Pregelatinized Starch 80g
Microcrystalline Cellulose 80g
The 2%HPMC aqueous solution is an amount of
Magnesium Stearate 3g
Prepare 1000 altogether
Prescription 4
Compound D or Compound D tetrahydrate 233g (in anhydrous compound)
Pregelatinized Starch 80g
Microcrystalline Cellulose 80g
The 2%HPMC aqueous solution is an amount of
Magnesium Stearate 3g
Prepare 1000 altogether
Prescription 5
Compd E or its hydrate 242g (in anhydrous compound)
Pregelatinized Starch 70g
Microcrystalline Cellulose 70g
The 2%HPMC aqueous solution is an amount of
Magnesium Stearate 3g
Prepare 1000 altogether
Prescription 6
Compound F 17-hydroxy-corticosterone or its hydrate 235g (in anhydrous compound)
Pregelatinized Starch 80g
Microcrystalline Cellulose 80g
The 2%HPMC aqueous solution is an amount of
Magnesium Stearate 3g
Prepare 1000 altogether
2, concrete steps
(1) raw material pulverizing is crossed 100 mesh sieves, all the other auxiliary materials are crossed 100 mesh sieves respectively, and are standby;
(2) hypromellose 2% the aqueous solution made soluble in water is standby;
(3) take by weighing raw material and auxiliary material according to recipe quantity;
(4) phenolsulfonic acid composite salt of the present invention or its hydrate, pregelatinized Starch, Microcrystalline Cellulose are mixed, it is an amount of to add the 2%HPMC aqueous solution, stirs, and makes suitable softwood;
(5) cross 20 mesh sieve system particles;
(6) particle is dried under 60 ℃ condition;
(7) dry good particle adds Magnesium Stearate, crosses the whole grain of 18 mesh sieves, mixes;
(8) sampling, the work in-process chemical examination;
(9) the sheet weight sheet of determining according to chemical examination;
(10) product are examined entirely, the packing warehouse-in.
The preparation of embodiment 38 phenolsulfonic acid composite salt of the present invention or its hydrate capsule
1, prescription:
Prescription 1
Compd A or compd A tetrahydrate 470g (in anhydrous compound)
Microcrystalline Cellulose 80g
Pregelatinized Starch 80g
The 2%HPMC aqueous solution is an amount of
Magnesium Stearate 3g
Prepare 1000 altogether
Prescription 2
Compd B or compd B tetrahydrate 468g (in anhydrous compound)
Pregelatinized Starch 80g
Microcrystalline Cellulose 80g
The 2%HPMC aqueous solution is an amount of
Magnesium Stearate 3g
Prepare 1000 altogether
Prescription 3
Compound C or Compound C tetrahydrate 468g (in anhydrous compound)
Pregelatinized Starch 80g
Microcrystalline Cellulose 80g
The 2%HPMC aqueous solution is an amount of
Magnesium Stearate 3g
Prepare 1000 altogether
Prescription 4
Compound D or Compound D tetrahydrate 464g (in anhydrous compound)
Pregelatinized Starch 80g
Microcrystalline Cellulose 80g
The 2%HPMC aqueous solution is an amount of
Magnesium Stearate 3g
Prepare 1000 altogether
Prescription 5
Compd E or its hydrate 484g (in anhydrous compound)
Pregelatinized Starch 70g
Microcrystalline Cellulose 70g
The 2%HPMC aqueous solution is an amount of
Magnesium Stearate 3g
Prepare 1000 altogether
Prescription 6
Compound F 17-hydroxy-corticosterone or its hydrate 470g (in anhydrous compound)
Pregelatinized Starch 80g
Microcrystalline Cellulose 80g
The 2%HPMC aqueous solution is an amount of
Magnesium Stearate 3g
Prepare 1000 altogether
2, concrete steps
(1) raw material pulverizing is crossed 100 mesh sieves, all the other auxiliary materials are crossed 100 mesh sieves respectively, and are standby;
(2) hypromellose 2% the aqueous solution made soluble in water is standby;
(3) take by weighing raw material and auxiliary material according to recipe quantity;
(4) phenolsulfonic acid composite salt of the present invention or its hydrate, pregelatinized Starch, Microcrystalline Cellulose are mixed, it is an amount of to add the 2%HPMC aqueous solution, stirs, and makes suitable softwood;
(5) cross 20 mesh sieve system particles;
(6) particle is dried under 60 ℃ condition;
(7) dry good particle adds Magnesium Stearate, crosses the whole grain of 18 mesh sieves, mixes;
(8) sampling, the work in-process chemical examination;
(9) loading amount of determining according to chemical examination incapsulates;
(10) finished product is examined entirely, the packing warehouse-in.
The preparation of embodiment 39 phenolsulfonic acid composite salt of the present invention or its hydrate liquid drugs injection
1, prescription:
Prescription 1
Compd A or compd A tetrahydrate 235g (in anhydrous compound)
Water for injection adds to 5000ml
Prepare 1000 altogether
Prescription 2
Compd B or compd B tetrahydrate 235g (in anhydrous compound)
Water for injection adds to 5000ml
Prepare 1000 altogether
Prescription 3
Compound C or Compound C tetrahydrate 234g (in anhydrous compound)
Water for injection adds to 5000ml
Prepare 1000 altogether
Prescription 4
Compound D or Compound D tetrahydrate 232g (in anhydrous compound)
Water for injection adds to 5000ml
Prepare 1000 altogether
Prescription 5
Compd E or its hydrate 242g (in anhydrous compound)
Water for injection adds to 5000ml
Prepare 1000 altogether
Prescription 6
Compound F 17-hydroxy-corticosterone or its hydrate 235g (in anhydrous compound)
Water for injection adds to 5000ml
Prepare 1000 altogether
2, concrete steps
(1) will produce with the ampoule dosing with vessel, plant and instrument etc. clear up, degerming, depyrogenation;
(2) take by weighing raw material and auxiliary material by prescription;
(3) with stirring and dissolving in the water for injection of phenolsulfonic acid composite salt of the present invention or its hydrate adding dosing amount 80%, the needle-use activated carbon temperature control of adding 0.1% stirred filtering decarbonization 10 minutes for 50 ℃;
(4) the pH value of survey solution, benefit adds to the full amount of water for injection, constant volume;
(5) soup is checked clarity through the smart filter of the millipore filtration of 0.22 μ m;
(6) inspection of semifinished product;
(7) the qualified back of inspection of semifinished product sealing by fusing is in ampoule;
(8) 100 ℃ of flowing steam sterilization 30min;
(9) while hot sample is put into 0.05% methylene blue solution and hunted leak, the lamp inspection;
(10) finished product is examined entirely, the packing warehouse-in.

Claims (9)

1,2 shown in the general formula (I), the composite salt of 5-dihydroxy benzenes sulfonic acid and hydrate thereof:
Wherein: A, B represent metallic element, all be selected from a kind of among Ca, Mg, the Zn, but A, B are inequality;
n 1, n 2The mole number of representing A, B respectively, n 1+ n 2=1, n 1/ n 2=(0.01～100): 1;
M1, m2 represent respectively A, B with the positive ion number;
And n 1* m1+n 2* m2=2;
N represents the number of crystal water, and its scope is 0～6.
2, according to claim 12, the composite salt of 5-dihydroxy benzenes sulfonic acid and hydrate thereof, wherein A is selected from Ca, and B is selected from a kind of among Mg, the Zn, n 1+ n 2=1, n 1/ n 2=(0.01～100): 1, m1, m2 are equal to 2, n=0 or n=n1+4n2.
3, according to claim 12, the composite salt of 5-dihydroxy benzenes sulfonic acid and hydrate thereof, wherein A, B are selected from Mg, Zn, n respectively 1+ n 2=1, n 1/ n 2=(0.01～100): 1, m1, m2 are equal to 2, n=0 or 4.
4, according to claim 32, the composite salt of 5-dihydroxy benzenes sulfonic acid and hydrate thereof, wherein A, B are selected from Mg, Zn respectively, and its mole ratio is: n 1/ n 2=(1～100): 1.
5, according to claim 42, the composite salt of 5-dihydroxy benzenes sulfonic acid and hydrate thereof, wherein A, B are selected from Mg, Zn respectively, and its mole ratio is: n 1/ n 2=(1～50): 1.
6, according to claim 52, the composite salt of 5-dihydroxy benzenes sulfonic acid and hydrate thereof, wherein A, B are selected from Mg, Zn respectively, and its mole ratio n 1/ n 2Be 3: 1,4: 1,5: 1,6: 1,9: 1,11: 1,19: 1.
7, clinically arbitrary or pharmaceutically acceptable formulation is characterized in that, described 2 by the arbitrary claim of claim 1～6, the composite salt of 5-dihydroxy benzenes sulfonic acid or its hydrate and auxiliary material are mixed and made into.
8, clinically according to claim 7 or pharmaceutically acceptable formulation is oral preparations or injection.
9, the arbitrary claim of claim 1～6 is described 2, the composite salt of 5-dihydroxy benzenes sulfonic acid or its hydrate in preparation as the application in the medicine of a kind of capillary blood vessel circulation activator and vasoprotector.
CNB200610131958XA 2006-05-30 2006-10-12 New medicinal compound salt of 2,5-dihydroxy benzenes sulfonic acid and hydrate thereof Active CN100534978C (en)

Priority Applications (1)

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CNB200610131958XA CN100534978C (en) 2006-05-30 2006-10-12 New medicinal compound salt of 2,5-dihydroxy benzenes sulfonic acid and hydrate thereof

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CN200610082106.6 2006-05-30
CN200610082106 2006-05-30
CNB200610131958XA CN100534978C (en) 2006-05-30 2006-10-12 New medicinal compound salt of 2,5-dihydroxy benzenes sulfonic acid and hydrate thereof

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