WO2010105454A1

WO2010105454A1 - Adenosine triphosphate intercalated hydrotalcite film and preparation method therefor

Info

Publication number: WO2010105454A1
Application number: PCT/CN2009/072079
Authority: WO
Inventors: 卫敏; 倪学云; 靳兰; 段雪
Original assignee: 北京化工大学
Priority date: 2009-03-18
Filing date: 2009-06-01
Publication date: 2010-09-23
Also published as: CN101530620B; CN101530620A

Abstract

The invention belongs to the technical field of biological-inorganic composites, and discloses an adenosine triphosphate (ATP) intercalated hydrotalcite film grown perpendicular to a substrate and a preparation method therefor. The invention uses an in-situ growth method to produce a hydrotalcite film to which ATP is then added. The specific steps are: first, forming an anodic aluminium oxide layer on the surface of a metallic aluminium, then producing a hydrotalcite film; next, immersing the hydrotalcite film into an ATP solution and drying it at room temperature to obtain an ATP intercalated hydrotalcite film. The advantages of the invention are that ATP is intercalated into the interlayer of hydrotalcite by applying an in-situ growth technique; this immobilizes the ATP, and achieves the slow release of target medicine by utilizing the interlayer confinement effect of hydrotalcite.

Description

Adenosine triphosphate intercalated hydrotalcite film and preparation method thereof

Technical field:

The invention belongs to the technical field of bio-inorganic composite materials, in particular to a vertical abasic growth adenosine triphosphate intercalated hydrotalcite film and a preparation method thereof. Background technique:

Layered Double Hydroxides (LDHs), an anionic layered inorganic functional material, as a high performance catalytic material, adsorbent material, separation material, functional additive material, biomaterial and Pharmaceutical materials are used in many industries of the national economy. Due to the problems of easy loss and difficult recycling of LDHs powder in practical applications, the emergence of LDHs membranes has attracted more and more attention. Previously, LDHs films prepared by solvent evaporation, layer-layer assembly and in-situ growth methods have been easy to recycle and improve the properties of materials.

In the literature (1) J. Am. Chem. Soc, 2006, 128: 4872-4880, Takayoshi Sasaki et al first stripped Co-Al hydrotalcite and then obtained the hydrotalcite laminate with layer-layer assembly method. A hydrotalcite film in which anionic polymers are alternately arranged provides a new method for preparing hydrotalcite films.

In the literature (2) Adv. Mater., 2006, 18: 3089-3093, Duan Xue et al. used in-situ synthesis technology to anodize the surface of the substrate by using the surface anodized aluminum sheet as the substrate. Aluminum provides the aluminum source needed for the growth of hydrotalcite. The pH of the reaction solution is adjusted by adding ammonia water, so that the Ni ²⁺ ions and NH ₃ in the solution grow under the near neutral condition, and the density is controlled to be perpendicular to the substrate growth. A nickel-aluminum nitrate hydrotalcite (NiAl-LDHs) film was found to have superhydrophobic properties.

In the literature (3) Chem. Mater., 2004, 16: 3774-3779, Duk-Young Jung et al. used a solvent evaporation technique to prepare a hydrotalcite film in which the layers were aligned parallel to the substrate direction on the basis of single crystal silicon. The authors believe that the morphology of the hydrotalcite in the ion exchange reaction and the variation of the interlayer spacing can be studied obviously after the hydrotalcite is formed into a film. There is currently no record of intercalated hydrotalcites for drug molecules. The inventors of the present invention have found that the advantage of hydrotalcite laminates (e.g., interlayer confinement) can be exploited by intercalating drug molecules between hydrotalcite layers.

Adenosine triphosphate can be used as an injection reagent for clinical use in heart failure, myocarditis, myocardial infarction, cerebral arteriosclerosis, coronary arteriosclerosis, acute polio, progressive muscular atrophy, and the like. The rate of absorption of the agent needs to be controlled during the injection to avoid potential hazards such as dizziness, head swelling, chest tightness and hypotension. By inserting adenosine triphosphate into the hydrotalcite layer, the purpose of the sustained release of the target drug can be achieved by utilizing the interlaminar restriction of hydrotalcite. Summary of the invention:

The object of the present invention is to provide a vertical abasic growth adenosine triphosphate intercalated hydrotalcite film and a preparation method thereof. The adenosine triphosphate (ATP) intercalated hydrotalcite film is a supramolecular structure, and its crystal structure maintains the crystal structure of the hydrotalcite material. Its chemical formula is:

[(M ²⁺ ) _1-x (M ³⁺ ) _x (OH ) ₂ ] ^x+ (ATP ³ -) _x/3 - m3⁄40 , where 0·2 χ 0·33, m is the number of crystal water molecules in the layer , and m = 3-6.

More specifically, M ²⁺ represents a divalent metal cation, for example, selected from the group consisting of Zn ²⁺ , Mg ²⁺ , Co ²⁺ , Ni ²⁺ , Ca ²⁺ , Cu ²⁺ , Fe ^{2+ ,} and Mn ^{2+ .} One or more of them, M ³⁺ represents a trivalent metal cation, and one of Al ³⁺ , Cr ³⁺ , Ga ³⁺ , In ³⁺ , Co ³⁺ , Fe ^{3+ ,} and V ³⁺ is selected Or several, preferably, said M ²⁺ represents Zn ²⁺ , Co ²⁺ or Ni ²⁺ , and said M ³⁺ represents Al ³⁺ .

The ATP ³ _ represents an anion of adenosine triphosphate.

The present invention employs an in situ growth technique to form an adenosine triphosphate intercalated hydrotalcite film material having a laminate aligned perpendicular to the anodized alumina substrate on an anodized alumina substrate. The specific preparation steps of the present invention are as follows:

a. Ultrasonic cleaning of aluminum flakes in anhydrous ethanol and deionized water for 2-10 min, then NaOH solution for 1-3 min, then rinsed with deionized water for 3-5 times, the cleaned aluminum flakes As Anode, lead sheet as cathode, 3⁄480 ₄ solution as electrolyte, constant voltage electrolysis, working voltage is 15-25 V, current is 1.5-3 A, electrolysis time is 0.5-2 h, electrolysis temperature is room temperature, in metal The surface of the aluminum forms an anodized aluminum layer to obtain an anodized aluminum/aluminum substrate, which is used after drying at 25-90 ° C. Preferably, the concentration of the NaOH solution is 0.1-0.4 M, more preferably 0.1-0.3 M. The concentration of the H ₂ S0 ₄ solution is 0.5-2 M, for example, may be 1-2 M, preferably 0.5-1 M;

b. Weigh the divalent metal salt and the NH ₄ NO ^ § solution separately into deionized water to form a reaction synthesis liquid, and then adjust the pH of the reaction synthesis solution to 5.9-8.5 with ammonia water, and the anodized aluminum/aluminum substrate is vertical. Suspension in the above reaction synthesis solution, reaction at 40-130 ° C for 12-96 h, after the reaction is completed, rinsed with deionized water for 3-5 times, and dried at room temperature to obtain a hydrotalcite-like film. Aluminum sheet. Preferably, the amount of the divalent metal salt contained per 150 ml of the reaction synthetic liquid is 0.005-0.06 mol, and the amount of the NH ₄ N0 ₃ substance is 0.005-0.09 mol; preferably every 150 ml of the described The amount of the divalent metal salt contained in the reaction synthesis liquid is 0.01-0.06 mol, and the amount of the NH ₄ N0 ₃ substance is 0.01-0.06 mol; more preferably, every 150 ml of the reaction synthetic liquid is contained The amount of the substance of the divalent metal salt is 0.015-0.03 mol, the amount of the substance of NH ₄ N0 ₃ is 0.03-0.06 mol; the mass fraction of the aqueous ammonia may be 1%-5%, preferably 1%-4%, more preferably 2%-3% _;

c Dissolving adenosine triphosphate in water to obtain adenosine triphosphate solution, adjusting the pH of the adenosine triphosphate solution to between 5.9 and 8.5, and then placing the aluminum sheet with hydrotalcite film prepared in step b at 40-130 ° C The reaction was carried out at a temperature of 12-96 h. After the reaction, the product was taken out, rinsed with deionized water for 3-5 times, and dried at room temperature to obtain a film of adenosine triphosphate intercalated hydrotalcite. Specifically, the concentration of the adenosine triphosphate solution is 0.5-2 g/L, preferably 1-2 g/L, and the mass fraction of ammonia water is 1% to 5%, preferably 1% to 4%, more preferably 2 %-3%.

The invention has the advantages that: by using the in situ growth technology, the adenosine triphosphate is inserted between the hydrotalcite layers to realize the immobilization of the adenosine triphosphate to achieve the sustained release of the target drug. BRIEF DESCRIPTION OF THE DRAWINGS: 1 is an X-ray powder diffraction pattern of an adenosine triphosphate intercalated hydrotalcite film on an anodized aluminum substrate prepared in Example 1.

Fig. 2 is a scanning electron microscope top view of the adenosine triphosphate intercalated hydrotalcite film prepared in Example 1. Figure 3 is a scanning electron micrograph of the adenosine triphosphate intercalated hydrotalcite film prepared in Example 1.

detailed description:

The invention is specifically illustrated by the following examples.

In the following examples, the mouths according to the present invention prepared in the respective examples were measured using the following method:

The structure was analyzed by a Shimadzu XRD-6000 X-ray diffractometer, Cu Ka source (λ = 0.154 nm), voltage 40 Kv, current 30 mA, continuous scanning, scanning speed 2 min.

Scanning electron microscopy characterization was performed on a Hitachi S-4700 scanning electron microscope (Hitachi, Japan).

Example 1

Step A: The aluminum piece was cut into pieces of lO cmxlO cm, ultrasonically cleaned in absolute ethanol and deionized water for 3 min, then placed in 0.1 M NaOH solution for 2 min, then rinsed with deionized water. The cleaned aluminum piece is used as the anode, the lead piece is used as the cathode, and the 1 M 3⁄4S0 ₄ solution is used as the electrolyte, and electrolysis is performed under constant pressure. The working voltage is 20 V, the current is 2 A, and the electrolysis time is 1 h. The electrolysis temperature is room temperature, thereby forming an anodized aluminum layer on the surface of the metal aluminum, and the obtained anodized aluminum/aluminum (AAO/A1) substrate is washed with a large amount of deionized water, and dried at 70 ° C for use;

Step B: Weigh 2.960 g of Zn(N0 ₃ ) ₂ · 6H ₂ O (0.01 mol) and 4.8 g of NH ₄ NO ₃ (0.06 mol), respectively, in deionized water to prepare 150 ml of the reaction synthesis solution, and then use 13⁄4 · 3⁄40 at a concentration of 1% adjusts the pH of the reaction synthesis solution to 6.5, and vertically hangs the anodized aluminum/aluminum substrate of the size 1 cm×2 cm prepared in the step A in the above reaction synthesis solution at 75 ° C Counter After 48 h, after the reaction, rinse with deionized water for 3 times, and dry at room temperature to obtain an aluminum sheet with a hydrotalcite film;

Step C: Weigh 0.1 g of adenosine triphosphate dissolved in deionized water to prepare 150 ml of adenosine triphosphate solution, and then adjust the pH of the adenosine triphosphate solution to 6.5 with a concentration of 1% ΝΗ ₃ · H ₂ 0. The aluminum piece of the hydrotalcite film was suspended vertically in the above reaction synthesis solution, and reacted at 75 ° C for 48 h. After the reaction, it was washed 5 times with deionized water and dried at room temperature to obtain a film of adenosine triphosphate intercalated hydrotalcite.

It can be seen from the X-ray diffraction pattern that the adenosine triphosphate intercalated hydrotalcite film prepared by in-situ growth method has a layer spacing of 1.640 Å; indicating that adenosine triphosphate successfully enters the hydrotalcite film layer. It can be seen from the plane and cross-sectional photographs of the scanning electron microscope that in the film, the hydrotalcite laminate is arranged perpendicular to the substrate, and the thickness of the film is about 0.45 μη. Example 2

Procedure Α: An anodized aluminum/aluminum substrate was obtained by the procedure of Example 1 in the procedure of Example 1.

Step B: Weigh 2.932 g of Co(N0 ₃ ) ₂ · 6H ₂ O (0.01 mol) and 4.8 g of NH ₄ NO ₃ <; 0.06 moi:) dissolved in deionized water to prepare 150 ml of the reaction synthesis solution. The pH of the reaction mixture was adjusted to 6.5 by using ΝΗ ₃ · H ₂ 0 at a concentration of 1%. The anodized aluminum/aluminum (AAO/A1) substrate having a size of 1 cm×2 cm prepared in the step A was vertically suspended in the above reaction synthesis solution, and reacted at 75 ° C for 48 h. After the completion of the reaction, the mixture was taken out, rinsed with deionized water, and dried at room temperature to obtain an aluminum sheet having a hydrotalcite film.

Step C: Weigh 0.15 g of adenosine triphosphate dissolved in deionized water to prepare 150 ml of adenosine triphosphate solution, and adjust the pH of the adenosine triphosphate solution to 6.5 with a concentration of 1% ΝΗ ₃ · H ₂ 0. The aluminum sheet with the hydrotalcite film is suspended vertically in the above reaction synthesis solution, and reacted at 75 ° C for 48 h. After the reaction, it is washed 5 times with deionized water and dried at room temperature to obtain adenosine triphosphate intercalated hydrotalcite. film. It can be seen from the X-ray diffraction pattern that the adenosine triphosphate intercalated hydrotalcite film prepared by in-situ growth method has a plate spacing of 1.656 nm; indicating that adenosine triphosphate successfully enters the hydrotalcite film layer. It can be seen from the plane and cross-sectional photographs of the scanning electron microscope that in the film, the hydrotalcite laminate is arranged perpendicular to the substrate, and the thickness of the film is about 0.45 μη. Example 3

Step Α: The AAO/A1 substrate was obtained by the procedure of Example 1 in Example 1.

Step B: Weigh 2.908 g of Ni(N0 ₃ ) ₂ · 6H ₂ O (0.01 mol) and 4.8 g of NH ₄ N0 ₃ (0.06 mol), respectively, in deionized water to prepare 100 ml of the reaction synthesis solution, and then The pH of the reaction mixture was adjusted to 6.5 with a concentration of 1% ΝΗ ₃ · 3⁄40. The anodized aluminum/aluminum (AAO/A1) substrate having a size of 1 cm×2 cm prepared in the step A was vertically suspended in the above reaction synthesis solution, and reacted at 75 ° C for 48 hours. After the completion of the reaction, the mixture was taken out, rinsed with deionized water, and dried at room temperature to obtain an aluminum sheet having a hydrotalcite film.

Step C: Weigh 0.15 g of adenosine triphosphate dissolved in deionized water to prepare 150 ml of adenosine triphosphate solution, and adjust the pH of the adenosine triphosphate solution to 6.5 with a concentration of 1% ΝΗ ₃ · H ₂ 0. The aluminum sheet with hydrotalcite film is suspended vertically in the above reaction synthesis solution, and reacted at 75 ° C for 48 h. After the reaction, it is washed 5 times with deionized water and dried at room temperature to obtain a film of adenosine triphosphate intercalated hydrotalcite. .

From the X-ray diffraction pattern, the adenosine triphosphate intercalated hydrotalcite film prepared by in-situ growth method has a plate spacing of 1.635 nm; indicating that adenosine triphosphate successfully enters the hydrotalcite film layer. It can be seen from the plane and cross-sectional photographs of the scanning electron microscope that in the film, the hydrotalcite laminate is arranged perpendicular to the substrate, and the thickness of the film is about 0.45 μη.

Claims

Claim

An adenosine triphosphate intercalated hydrotalcite film, characterized in that the film is a supramolecular structure, and the crystal structure of the film is a crystal structure of a hydrotalcite material, and the chemical formula is:

[(M ²⁺ ) _1-x (M ³⁺ ) _x (OH ) ₂ ] ^x+ (ATP ³ -)x/3 - m3⁄40 , wherein 0·2 χ 0·33 _; ATP ³ - represents an anion of adenosine triphosphate, m is the number of crystal water molecules in the interlayer, and m = 3-6.

The adenosine triphosphate intercalated hydrotalcite film according to claim 1, wherein the M ²⁺ is selected from the group consisting of Zn ²⁺ , Mg ²⁺ , Co ²⁺ , Ni ²⁺ , Ca ²⁺ , Cu ^{2 .} a divalent metal cation of one or more of ⁺ , Fe ²⁺ and Mn ²⁺ , wherein said M ³⁺ is selected from the group consisting of Al ³⁺ , Cr ³⁺ , Ga ³⁺ , In ³⁺ , Co ³⁺ , A trivalent metal cation of one or more of Fe ³⁺ and V ³⁺ .

The adenosine triphosphate intercalated hydrotalcite film according to claim 2, wherein the M ²⁺ is Zn ²⁺ , Co ²⁺ or Ni ²⁺ , and the M ³⁺ is Al ³⁺ .

A method for preparing an adenosine triphosphate intercalated hydrotalcite film, characterized in that the preparation method comprises:

a. The aluminum sheets are ultrasonically cleaned in absolute ethanol and deionized water for 2-10 min, then placed in NaOH solution for l-3 min, rinsed with deionized water, and the cleaned aluminum sheet is used as an anode. The lead piece is used as the cathode, and the 3⁄480 ₄ solution is used as the electrolyte. The electrolysis is carried out under constant pressure. The working voltage is 15-25 V, the current is 1.5-3 A, the electrolysis time is 0.5-2 h, and the electrolysis temperature is room temperature, thereby Anodized aluminum layer is formed on the surface of the aluminum, and the obtained anodized aluminum/aluminum substrate is washed with deionized water and dried at 25-90 ° C;

b. Weigh the soluble divalent metal salt and NH ₄ N0 _{3 separately} dissolved in deionized water to form a reaction synthesis liquid, and then adjust the pH of the reaction synthesis solution to 5.9-8.5 with ammonia water, and prepare the anode prepared in step a. The alumina/aluminum substrate is suspended vertically in the above reaction synthesis solution, and reacted at a temperature of 40-130 ° C for 12-96 h. After the reaction, rinse with deionized water for 3-5 times, and dry at room temperature to obtain a long Aluminum sheet of hydrotalcite film; C. Dissolving adenosine triphosphate in water to prepare adenosine triphosphate solution, and adjusting the pH of the adenosine triphosphate solution to between 5.9 and 8.5 with ammonia water, and then placing the aluminum sheet with hydrotalcite film prepared in step b, at 40 The reaction is carried out at a temperature of -130 ° C for 12-96 h. After the reaction is completed, the obtained product is washed with deionized water for 3-5 times, and dried at room temperature to obtain a film of adenosine triphosphate intercalated hydrotalcite; the aluminum sheet, adenosine triphosphate and The amount of the divalent metal salt is such that the film of the adenosine triphosphate intercalated hydrotalcite has the following chemical formula:

[(M ²⁺ ) _1-x (M ³⁺ ) _x (OH ) ₂ ] ^X+ (ATP ³ ) _x/3 -mH ₂ 0, wherein 0·2 χ 0·33 _; ATP ³ - represents an anion of adenosine triphosphate m is the number of crystal water molecules in the interlayer, and m = 3-6.

The preparation method according to claim 4, wherein the concentration of the NaOH in the step a is 0.1-0.4 M, and the concentration of the H ₂ S0 ₄ solution is 1-2 M.

The preparation method according to claim 5, wherein, in the step b, the amount of the divalent metal salt contained in each of the 150 ml of the reaction synthetic liquid is 0.01-0.06 mol, NH ₄ N0 ₃ The amount of the substance is 0.01-0.06 mol; the mass fraction of the ammonia water is 1%-4%.

The preparation method according to claim 4, wherein the concentration of the adenosine triphosphate solution in the step c is 1-2 g/L, and the mass fraction of the ammonia water is 1% to 4%.

The preparation method according to any one of claims 4 to 7, wherein the divalent metal cation in the soluble divalent metal salt is selected from the group consisting of Zn ²⁺ , Mg ²⁺ , Co ²⁺ , Ni ^{2 One or more of +} , Ca ²⁺ , Cu ²⁺ , Fe ²⁺ and Mn ²⁺ .

The production method according to claim 8, wherein the divalent metal cation in the soluble divalent metal salt is Zn ²⁺ , Co ²⁺ or Ni ²⁺ .