CN100998871A - Chiral medicine D-antothenic acid intercalation hydrotalcite and its preparation method - Google Patents
Chiral medicine D-antothenic acid intercalation hydrotalcite and its preparation method Download PDFInfo
- Publication number
- CN100998871A CN100998871A CNA2007100627662A CN200710062766A CN100998871A CN 100998871 A CN100998871 A CN 100998871A CN A2007100627662 A CNA2007100627662 A CN A2007100627662A CN 200710062766 A CN200710062766 A CN 200710062766A CN 100998871 A CN100998871 A CN 100998871A
- Authority
- CN
- China
- Prior art keywords
- chiral
- antothenic
- medicine
- acid
- hydrotalcite
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
Images
Landscapes
- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
A chiral medicine D-pantothenic acid intercalated hydrotalcite with high thermal stability and optical stability and a certain slow-release nature has a chemical formula: (Mn+)1-x(M3+)x(OH)a(D-C9H16NO5)6.mH2O. Its preparing process includes such steps as preparing the precursor of hydrotalcite by single-drop codeposition method, and ion exchange reaction with the calcium D-pantothenate solution in ultrasonic generator.
Description
Technical field
The invention belongs to the vitamin drug technical field, a kind of chiral medicine D-antothenic acid (D-C particularly is provided
9H
17NO
5) intercalated houghite and preparation method thereof.
Technical background
Pantothenic acid (Pantothenic acid) is a kind of of vitamin, is the ingredient of coenzyme A.Pantothenic acid has optical activity, medicinal R type dextroisomer, and clinical most its calcium salt of using.When human body lacked pantothenic acid, symptoms such as headache, motor function imbalance and digestive functional disturbance can appear.Additional pantothenic acid can make above-mentioned symptom alleviate or disappearance.Pantothenic acid can be used as the important ancillary drug of treatment leukopenia arteriosclerosis and myocardial infarction, also is used as Energy mixture together in ATP, insulin.
Pantothenic acid extensively is present in the protoplasm of animal vegetable tissue cell, and is the abundantest with content in yeast, liver, egg yolk, Fructus Hordei Germinatus, the Testa oryzae.All vertebratess all need pantothenic acid, human body pantothenic acid requirement every day about 10mg, wet nurse or heavy worker then need 20mg every day.
D-pantothenic acid is the pantothenic acid dextrorotation enantiomer that plays active function in organism.Often have only a kind of enantiomer to have the effect of treatment for chiral drug, another kind of enantiomer non-activity or activity are very low, even the enantiomer of drugs that has is deleterious to human body.Chiral drug market grows stronger day by day in recent years, realizes that the single enantiomer administration is the inexorable trend of clinical administration.Thereby reduce drug effect but racemization takes place the medicine of single enantiomer easily in the process of storing, therefore concerning this class medicine, must preserve covering under light and the sealing of strictness.The optical stability and the heat stability that how better to keep the single enantiomer medicine are new problems that realizes that its commercialization faces afterwards.Though brucite (LDHs) has been widely used in field of medicaments (as gastric antiacids, anti-inflammatory agent, anti-osteoporotic etc.), still there be not document and the patent report that relevant hydrotalcite stratified material is applied to vitamins chiral drug field at present both at home and abroad.
Summary of the invention
The object of the present invention is to provide a kind of chiral medicine D-antothenic acid (D-C
9H
17NO
5) intercalated houghite and preparation method thereof, obtain a kind of drug effect storing and taking brucite vitamin drug relatively stable in the process, to solve the restriction of this chiral drug of present D-pantothenic acid on the storage condition.
Chiral drug intercalation hydrotalcite vitamin drug of the present invention can keep the configuration of chiral drug to guarantee drug effect in its storage process by the space confinement effect of hydrotalcite layers; Take the effect that can play the drug effect slow release in the process by the host-guest interaction of brucite laminar composite at it, main body wherein also can play the effect of controlled release agent simultaneously.
The chemical formula of this chiral drug intercalation hydrotalcite is: (M
N+)
1-x(M
3+)
X(OH)
a(D-C
9H
16NO
5)
bMH
2O (n=1 or 2).At first preparing interlayer anion is NO
3 --Perhaps Cl
--The brucite precursor, then the chiral medicine D-antothenic acid anion is replaced NO through ion exchange
3 --Perhaps Cl
--Enter hydrotalcite layers, constitute the anionic supermolecule stratified material that the chiral medicine D-antothenic acid anion accounts for interlayer anion molal quantity sum 20～80%; This material can make full use of the space confinement effect of its interlayer and the interaction between the Subjective and Objective, chiral drug is played the storage and the slow-release function of continuous and effective.The interlayer object decomposes just beginning more than 260 ℃, i.e. good thermal stability.Can keep the interlayer object more than 90% that raceme does not take place generally speaking, promptly have significantly effectively storage performance.Described M
N+Be Li
+, Zn
2+, Ca
2+In any, M
3+Be Al
3+, Fe
3+In any.
Chiral medicine D-antothenic acid intercalation hydrotalcite preparation process of the present invention is as follows:
A. prepared layer flaggy plate monovalence, Tricationic mol ratio M
+/ M
3+=0.5～3.0 or bivalence, Tricationic mol ratio M
2+/ M
3+=2.0～4.0, interlayer anion is NO
3 --Perhaps Cl
--The brucite precursor;
B. the calcium salt with chiral medicine D-antothenic acid joins in the water of 60～120ml, makes its dissolving, thereby obtains including the anionic solution of electronegative chiral medicine D-antothenic acid;
C. according to chiral medicine D-antothenic acid, brucite precursor mol ratio D-Pa/Pre-LDHs=2.0～12.0, with the brucite precursor of step a preparation in ultrasonic generator and at N
2Protection down, (2～6h), product spends CO with carrying out ion-exchange reactions under 40～60 ℃ of the anionic solution of chiral medicine D-antothenic acid
2, the abundant centrifuge washing of deionized water separates 3～4 times; Can obtain chiral medicine D-antothenic acid intercalation hydrotalcite behind 40～60 ℃ of vacuum dryings.
Brucite main body laminate of the present invention is selected cation Li
+, Zn
2+, Ca
2+In any and Al
3+, Fe
3+In any combination.
With above-mentioned prepared material:
1. carry out XRD, IR, NMR, elemental analysis demonstration chiral medicine D-antothenic acid in the success of hydrotalcite layers intercalation.The composite interlamellar spacing of XRD data show after chirality is medicament intercalated increases, and its cell parameter a value remains unchanged in the intercalation front and back, has complete layer structure;
2. carrying out TG-DTA, TG-MAS characterize to show that the heat stability of this composite has had and significantly improves;
3. carry out polariscope, its optical stability maintenance of chiral column HPLC sign demonstration well;
4. carry out in-vitro simulated release experiment and show that this composite system can reach certain sustained release performance.
The invention has the advantages that: utilize the space confinement effect of brucite stratified material and the interaction between the Subjective and Objective, the vitamins chiral medicine D-antothenic acid intercalation is entered hydrotalcite layers, realize the effective storage of brucite chiral drug; Reach the sustained release performance of brucite simultaneously, for " storage-administration " new way that brucite is applied to this chiral drug is provided fundamental basis to this chiral drug.
Description of drawings
The XRD spectra of Fig. 1 for obtaining under the specific embodiment of the invention condition; Abscissa is 2 θ, unit: degree; Vertical coordinate is an intensity.Wherein: a is D-Pa/LDHs; B is NO
3-ZnAl/LDHs.
Fig. 2 is the variation of the intercalation product that obtains under the specific embodiment of the invention condition and pure D-pantothenic acid specific rotatory power under the irradiation under ultraviolet ray different time; Abscissa is the time, unit: hour; Vertical coordinate is the decline of specific rotatory power.Wherein: a is D-Pa/LDHs; B is pure D-Pa.
The specific embodiment
Steps A: take by weighing 35.6g Zn (NO
3)
26H
2O and 22.60g Al (NO
3)
39H
2O is dissolved in 150ml and removes CO
2, deionized water preparation mixing salt solution, other gets 14.4g NaOH and is dissolved in 200ml and removes CO
2, deionized water and being positioned in the 500mL four-hole boiling flask; Adopt single coprecipitation, at 70 ℃ of water-baths, N
2Under protection, the strong agitation condition the former saline solution slowly is added drop-wise in latter's aqueous slkali, regulates about pH value to 6.0, reaction 40h; The product washing and filtering is to pH＜8.0; Keep a large amount of fresh filter cakes in order to ion exchange usefulness, only take out small amount of sample and characterize behind the dry 18h down, obtain NO at 70 ℃
3-Zn
2Al-LDHs, its Zn
2+/ Al
3+=2.
Step B:, take by weighing the 2.0gD-calcium pantothenate earlier and be dissolved in 80mL and remove CO according to D-Pa/Pre-LDHs=4
2, deionized water and place the 250mL conical flask; Take by weighing 1.5g again and add wherein N by the filter cake that steps A makes
2Protect, conical flask put into ultrasonic generator, power 90W, 50 ℃ of ion exchange 3h; Product spends CO
2, deionized water wash centrifugalize 3～4 times, will precipitate 50 ℃ of dryings in a vacuum, can obtain the anion intercalated laminar composite of D-pantothenic acid.
Step C: the specific rotatory power test, a certain amount of D-calcium pantothenate is placed irradiation 48h under the uviol lamp, took out 0.2g every four hours, with 1: 1 dissolve with hydrochloric acid solution, accurately be settled to 50ml, measure its optical rotation.The optical rotation of taking same step to measure D-Pa/LDHs is drawn the drop-out value of specific rotatory power respectively to irradiation under ultraviolet ray time relation curve.
By XRD figure as can be known, the D-Pa anion is after ion exchange enters the LDHs interlayer, and its laminate spacing increases to 1.56nm by the 0.92nm of precursor, proves the anion intercalated success of D-Pa; Two kinds of LDHs have the obvious diffraction peak near 2 θ are 61 °, and corresponding cell parameter α is approximately 0.30nm, illustrates that the anion intercalated front and back of D-Pa LDHs laminate charge density does not change, and the LDHs laminate obtains more complete maintenance.By the heat analysis as can be known, the interlayer object of composite decomposes just beginning more than 260 ℃, illustrates that its heat stability increases significantly.By optical activity test as can be known, pure D-calcium pantothenate irradiation under ultraviolet ray after 48 hours specific rotatory power descended 35% approximately, and D-pantothenic acid specific rotatory power has only faint decline behind the intercalation, illustrate that LDHs has D-pantothenic acid significantly effectively to store performance.
Claims (4)
1. a chiral medicine D-antothenic acid intercalation hydrotalcite is characterized in that, chemical formula is: (M
N+)
1-x(M
3+)
x(OH)
a(D-C
9H
16NO
5)
bMH
2O, n=1 or 2; Interlayer anion is NO
3 -Perhaps Cl
-The brucite precursor, the chiral medicine D-antothenic acid anion replaces NO through ion exchange
3 -Perhaps Cl
-Enter hydrotalcite layers, constitute the anionic supermolecule stratified material that the chiral medicine D-antothenic acid anion accounts for interlayer anion molal quantity sum 20～80%; This material can make full use of the space confinement effect of its interlayer and the interaction between the Subjective and Objective, chiral drug is played the storage and the slow-release function of continuous and effective.
2, according to the described chiral medicine D-antothenic acid intercalation hydrotalcite of right l, it is characterized in that M
N+Be Li
+, Zn
2+, Ca
2+In any, M
3+Be Al
3+, Fe
3+In any.
3. method for preparing right 1 described chiral drug intercalation hydrotalcite, its preparation process is:
A. preparing interlayer anion is NO
3 -Perhaps Cl
-, laminate monovalence, Tricationic mol ratio M
+/ M
3+=0.5～3.0 or bivalence, Tricationic mol ratio M
2+/ M
3+=2.0～4.0 brucite precursor;
B. the calcium salt with chiral medicine D-antothenic acid joins in the water of 60～120ml, makes its dissolving, thereby obtains including the anionic solution of electronegative chiral medicine D-antothenic acid;
C. according to chiral medicine D-antothenic acid, brucite precursor mol ratio D-Pa/Pre-LDHs=2.0～12.0, in ultrasonic generator and at N
2Under the protection, 40～60 ℃ are carried out ion-exchange reactions 2～6h, and product spends CO
2, the abundant centrifuge washing of deionized water separates 3～4 times; , behind 40～60 ℃ of vacuum dryings, obtain chiral drug intercalation hydrotalcite.
4. according to right 3 described preparation methoies, it is characterized in that: brucite main body laminate is selected monovalence metal cation Li
+With trivalent metal cation Al
3+, Fe
3+In any combination or select divalent metal Zn
2+, Ca
2+In any and trivalent metal cation Al
3+, Fe
3+In any combination.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNA2007100627662A CN100998871A (en) | 2007-01-16 | 2007-01-16 | Chiral medicine D-antothenic acid intercalation hydrotalcite and its preparation method |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNA2007100627662A CN100998871A (en) | 2007-01-16 | 2007-01-16 | Chiral medicine D-antothenic acid intercalation hydrotalcite and its preparation method |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN100998871A true CN100998871A (en) | 2007-07-18 |
Family
ID=38257743
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CNA2007100627662A Pending CN100998871A (en) | 2007-01-16 | 2007-01-16 | Chiral medicine D-antothenic acid intercalation hydrotalcite and its preparation method |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN100998871A (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105214102A (en) * | 2015-10-22 | 2016-01-06 | 北京化工大学 | A kind of supermolecule composite optothermal reagent and the application in photo-thermal therapy and near infrared imaging thereof |
-
2007
- 2007-01-16 CN CNA2007100627662A patent/CN100998871A/en active Pending
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105214102A (en) * | 2015-10-22 | 2016-01-06 | 北京化工大学 | A kind of supermolecule composite optothermal reagent and the application in photo-thermal therapy and near infrared imaging thereof |
| CN105214102B (en) * | 2015-10-22 | 2018-10-23 | 北京化工大学 | A kind of supermolecule composite optothermal reagent and its application in terms of photo-thermal therapy and near infrared imaging |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Shi et al. | Carbon dots anchored high-crystalline gC 3 N 4 as a metal-free composite photocatalyst for boosted photocatalytic degradation of tetracycline under visible light | |
| Zhao et al. | Preparation of layered double-hydroxide nanomaterials with a uniform crystallite size using a new method involving separate nucleation and aging steps | |
| EP1341556B1 (en) | Drug delivery system | |
| Tarasov et al. | Solid-state chelation of metal ions by ethylenediaminetetraacetate intercalated in a layered double hydroxide | |
| CN100354203C (en) | Amino acid intercalation manganese dioxide and its preparation method | |
| CN101774599A (en) | Modified na-montmorillonite, preparation method and application thereof | |
| US7687650B2 (en) | Chemical compositions and methods of making them | |
| EP3789345A1 (en) | Composite composition | |
| Chen et al. | Trends in Layered Double Hydroxides‐Based Advanced Nanocomposites: Recent Progress and Latest Advancements | |
| CN102531036B (en) | Magnesium-zinc-aluminum ternary hydrotalcite-like compound heat stabilizer for PVC (Poly Vinyl Chloride) and preparation method of magnesium-zinc-aluminum ternary hydrotalcite heat stabilizer | |
| Mary et al. | Phytochemical assisted synthesis of Ni doped ZnO nanoparticles using aloe vera extract for enhanced photocatalytic and antibacterial activities. | |
| CN100998872B (en) | Polypeptide medicine intercalation hydrotalcite and its preparation method | |
| CN101607091B (en) | Method for synthesizing dextran-magnetic LDH-fluorouracil magnetic targeting sustained and controlled release tripolymer | |
| CN100998871A (en) | Chiral medicine D-antothenic acid intercalation hydrotalcite and its preparation method | |
| CN102631685A (en) | Coprecipitation method for preparing methotrexate/ layered double hydroxides nanocomposite material | |
| CN101785860A (en) | Tegafur/layered duplex metal hydroxide nanometer hybrid and preparation method thereof | |
| CN109694095A (en) | The preparation method of high-ratio surface nano hydrotalcite | |
| Choi et al. | Facile room-temperature synthesis of cerium carbonate and cerium oxide nano-and microparticles using 1, 1′-carbonyldiimidazole and imidazole in a nonaqueous solvent | |
| CN106857656A (en) | A kind of compound hydrotalcite type nano material of ruthenium complex joint Nano Silver and its production and use | |
| CN102309513A (en) | Application of drug composition in preparation of drugs for treating hypertensive disease | |
| Norman et al. | Crystal structure of a copper complex of 2-carboxypentonic acid; a decomposition product of dehydroascorbic acid | |
| Ströbele et al. | Struktur und elektrochemische Untersuchung von Nb3Cl8 | |
| CN103191049A (en) | Tegafur/layered double hydroxide (TF/LDHs) nanohybrid-magnetic matrix compound and preparation method thereof | |
| CN103266353B (en) | Sandwich-type bismuth tungstate compound with methylimidazole simultaneously as counter ion and modified group and preparation method and application thereof | |
| CN1850275A (en) | Chiral drug intercalation hydrotalcite and its preparing method |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C12 | Rejection of a patent application after its publication | ||
| RJ01 | Rejection of invention patent application after publication |
Open date: 20070718 |