CN111744017B - Ibuprofen intercalation magnalium hydrotalcite sustained-release material and preparation method thereof - Google Patents
Ibuprofen intercalation magnalium hydrotalcite sustained-release material and preparation method thereof Download PDFInfo
- Publication number
- CN111744017B CN111744017B CN202010657186.3A CN202010657186A CN111744017B CN 111744017 B CN111744017 B CN 111744017B CN 202010657186 A CN202010657186 A CN 202010657186A CN 111744017 B CN111744017 B CN 111744017B
- Authority
- CN
- China
- Prior art keywords
- ibuprofen
- hydrotalcite
- release material
- sustained
- preparation
- 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.)
- Active
Links
Images
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/02—Inorganic compounds
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
- A61K31/19—Carboxylic acids, e.g. valproic acid
- A61K31/192—Carboxylic acids, e.g. valproic acid having aromatic groups, e.g. sulindac, 2-aryl-propionic acids, ethacrynic acid
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
Abstract
The invention relates to an ibuprofen intercalation magnalium hydrotalcite sustained-release material and a preparation method thereof, and specifically comprises the steps of respectively dissolving soluble magnesium salt and sodium aluminate in deionized water, adding an alkaline precipitator and soluble carbonate, stirring and reacting at a constant temperature and a constant speed for 30-120 minutes at 90-100 ℃, standing and cooling, then carrying out suction filtration, washing, drying and grinding to obtain magnalium hydrotalcite; transferring the hydrotalcite into a tubular furnace, introducing nitrogen for protection, heating to 450-600 ℃ from room temperature, preserving the temperature for 1-5 hours to obtain calcined hydrotalcite, adding the calcined hydrotalcite into an ethanol solution of ibuprofen, uniformly dispersing, adjusting the pH, reacting for 4-6 hours at the temperature of 60-80 ℃, performing suction filtration, vacuum drying and grinding. The ibuprofen intercalation magnalium hydrotalcite sustained-release material is mainly characterized in that: the space between the layers of the ibuprofen intercalation magnalium hydrotalcite slow release material is further enlarged, ibuprofen is successfully inserted between hydrotalcite laminates in a-COO-ion form and forms hydrogen bonds with hydroxyl on the laminates, the combination is good, the slow release performance is excellent, and the ibuprofen intercalation magnalium hydrotalcite slow release material can be used in the field of drug carriers.
Description
Technical Field
The invention belongs to the field of medicinal carriers, particularly relates to a sustained-release material and a preparation method thereof, and more particularly relates to an ibuprofen intercalation magnalium hydrotalcite sustained-release material and a preparation method thereof.
Background
Serious toxic and side effects of the medicine always plague the medical field, and the research of a novel high-efficiency low-toxic-side-effect medicine sustained-release administration system becomes an important subject of pharmacy and materials. The ideal drug carrier should have biocompatibility, biostability, extremely low toxicity and good drug release performance. The Layered plate composition of hydrotalcite (LDHs) has adjustable property, and the species and proportion of divalent and trivalent metal elements can be adjusted to obtain Layered material with special property and functional structure. Because the hydrotalcite laminate has stronger covalent bond function and interlayer anions have exchangeable characteristics and are combined with the laminate by ionic bonds, hydrogen bonds and van der waals forces, the medicament can be inserted into the hydrotalcite interlayer due to the supermolecular structure, and the medicament can realize effective controlled release of the medicament by adjusting the hydrotalcite structure due to the hydrogen bond function, steric hindrance and the like between the medicament and the laminate, and the hydrotalcite laminate is widely used as a slow release carrier of the medicament in recent years and becomes one of research hotspots.
At present, the main preparation methods of the drug intercalation hydrotalcite include a coprecipitation method, an ion exchange method, a roasting recovery method and a stripping-reassembly method. The hydrotalcite is assembled by taking 5-fluorouracil, curcumin, cucurbitacin, cefepime, norfloxacin, chlorpyrifos and the like as guest molecules through intercalation, the controlled release of the drug can be realized under certain conditions, and the hydrotalcite has good drug slow release effect. Ibuprofen is a common non-steroidal anti-inflammatory, antipyretic and analgesic drug and is mainly used for relieving mild and moderate pains such as headache, toothache, dysmenorrheal and the like, and ibuprofen has poor water solubility and short half-life, so that the clinical application of ibuprofen is influenced.
The present application has been made for the above reasons.
Disclosure of Invention
The invention aims to provide an ibuprofen intercalation magnalium hydrotalcite sustained-release material and a preparation method thereof. The technical problem to be solved by the invention is as follows: aiming at the problems that ibuprofen serving as a non-steroidal anti-inflammatory, antipyretic and analgesic drug has poor water solubility and short half-life period and affects clinical application of ibuprofen, the invention provides an ibuprofen intercalation magnalium hydrotalcite sustained-release material.
In order to achieve one of the above objects of the present invention, the present invention adopts the following technical solutions:
a preparation method of ibuprofen intercalation magnalium hydrotalcite sustained-release material comprises the following steps:
(1) Weighing soluble magnesium salt and sodium aluminate in sequence according to the proportion, then respectively dissolving the soluble magnesium salt and the sodium aluminate in deionized water to obtain a magnesium salt aqueous solution and a sodium aluminate aqueous solution, and then uniformly mixing the magnesium salt aqueous solution and the sodium aluminate aqueous solution to obtain a mixed solution 1;
(2) Adding an alkaline precipitator and soluble carbonate into the mixed solution 1 obtained in the step (1), uniformly mixing to obtain a mixed solution 2, heating the mixed solution 2 to 90-100 ℃, stirring at a constant temperature and a constant speed at the temperature of 90-100 ℃ for reaction for 30-120 minutes, standing and cooling after the reaction is finished, carrying out suction filtration, washing, drying and grinding on the obtained product to obtain the magnalium hydrotalcite;
(3) Putting the magnesium-aluminum hydrotalcite obtained in the step (2) into a crucible, then transferring the crucible into a tubular furnace, introducing nitrogen for protection, heating the tubular furnace from room temperature to 450-600 ℃, and calcining for 1-5 hours at 450-600 ℃ under the protection of nitrogen atmosphere to obtain calcined hydrotalcite;
(4) And (3) adding the calcined hydrotalcite obtained in the step (3) into an ethanol solution of ibuprofen according to a ratio, fully stirring to form a suspension, adjusting the pH of the obtained suspension to 5-6, heating to 60-80 ℃, reacting at a constant temperature for 4-6 hours, after the reaction is finished, performing suction filtration, vacuum drying and grinding to obtain the ibuprofen intercalation magnalium hydrotalcite slow-release material.
Further, in the above technical solution, the soluble magnesium salt in the step (1) is any one or more of magnesium chloride, magnesium nitrate, magnesium sulfate, and the like. In a preferred embodiment of the invention, the soluble magnesium salt is magnesium chloride hexahydrate.
Further, in the technical scheme, the molar ratio of the soluble magnesium salt to the sodium aluminate in the step (1) is 2-4.
Further, in the technical scheme, the molar ratio of the alkaline precipitator, the soluble carbonate and the soluble magnesium salt in the step (2) is (0.2-1): (0.025-0.2): 0.2-0.25).
Further, in the above technical solution, the alkaline precipitant in step (2) is any one of sodium hydroxide, potassium hydroxide, calcium hydroxide, and the like. In a preferred embodiment of the invention, the alkaline precipitant is sodium hydroxide.
Further, in the above technical scheme, the soluble carbonate in the step (2) is any one of sodium carbonate, potassium carbonate, ammonium carbonate or ammonium bicarbonate. In a preferred embodiment of the invention, the soluble carbonate is sodium carbonate.
Further, according to the technical scheme, the stirring speed in the step (2) is 400-800 revolutions per minute.
Further, according to the technical scheme, the particle size of the magnesium-aluminum hydrotalcite ground in the step (2) is 500-1000 nm.
In a preferred embodiment of the present invention, the solvent used to wash the product in step (2) is preferably deionized water.
Further, according to the technical scheme, the process for drying the product in the step (2) comprises the following steps: the drying temperature is 50-70 ℃, and the drying time is 4-6 hours. In a preferred embodiment of the present invention, the drying temperature is 60 ℃.
Further, according to the technical scheme, the temperature rise rate of the tube furnace in the step (3) is 1-10 ℃/min. In a preferred embodiment of the present invention, the temperature increase rate is 5 ℃/min.
In a preferred embodiment of the present invention, the temperature of the soak calcination in the step (3) is 500 ℃.
In a preferred embodiment of the present invention, the time for the soaking calcination in the step (3) is 3 hours.
Further, according to the technical scheme, the mass fraction of the ibuprofen in the ethanol solution of the ibuprofen in the step (4) is 0.5-1.0%.
Further, in the above technical scheme, the usage ratio of the calcined hydrotalcite to ibuprofen in step (4) is 100.
In a preferred embodiment of the present invention, the temperature of the vacuum drying in the step (4) is 60 ℃ and the time of the vacuum drying is 24 hours.
The second purpose of the invention is to provide the ibuprofen intercalation magnalium hydrotalcite sustained-release material prepared by the method.
Compared with the prior art, the invention has the following beneficial effects:
(1) The invention can improve the thermal stability of ibuprofen in vivo and improve the solubility of ibuprofen by intercalating and assembling the ibuprofen and the magnesium-aluminum hydrotalcite, can realize the controlled release of the molecular level of the ibuprofen by utilizing the magnesium-aluminum hydrotalcite laminated slab structure, interlayer hydrogen bonds and the like, reduces the toxic and side effects and burst release of the ibuprofen, improves the bioavailability of the ibuprofen, enhances the clinical curative effect of the ibuprofen, and has important application value.
(2) The ibuprofen intercalation magnalium hydrotalcite prepared by the invention has controllable interlayer spacing. The interlayer spacing of the magnesium-aluminum hydrotalcite can be regulated and controlled by changing the reaction conditions (such as reaction temperature, reaction time and the like) for synthesizing the magnesium-aluminum hydrotalcite, meanwhile, the interlayer spacing of the magnesium-aluminum hydrotalcite can be further increased by calcining, more ibuprofen molecules can be contained, and the interlayer spacing of the ibuprofen intercalation magnesium-aluminum hydrotalcite is enlarged to 2.594nm, so that the drug loading rate can be improved.
(3) The ibuprofen intercalated magnalium hydrotalcite prepared by the invention has excellent slow release performance. The ibuprofen intercalation magnalium hydrotalcite sustained-release material prepared by the invention has the ibuprofen of-COO - The ions are successfully inserted between the hydrotalcite laminates and form hydrogen bonds with hydroxyl groups on the laminates, so that the controlled release of ibuprofen in molecular level is realized, and the toxic and side effects and burst release of ibuprofen are reduced. The drug release of the ibuprofen intercalated magnalium hydrotalcite mainly comprises two stages, wherein the first stage is within 120min, the drug release speed is relatively high, but no burst release phenomenon exists, and the drug release belongs to a physical diffusion process; the second stage is 120min later, the slow release speed is mainly that ibuprofen loaded between the intercalation and the calcined hydrotalcite interlayer is slowly released from interlayer diffusion. Drug release is dominated by diffusion.
(4) The invention is simple and convenient to operate. The invention has simple preparation, is convenient for realizing industrial production and has very wide application prospect.
Drawings
Fig. 1 is XRD patterns of magnesium aluminum hydrotalcite and calcined hydrotalcite prepared in example 1, example 2, example 3 and example 4.
Fig. 2 is an XRD pattern of ibuprofen intercalated magnesium aluminum hydrotalcite sustained release material prepared in example 1, example 2, example 3 and example 4.
Fig. 3 is SEM images of magnesium aluminum hydrotalcite prepared in example 1, example 2, example 3, and example 4, and respectively shows fig. 3 (a), fig. 3 (b), fig. 3 (c), and fig. 3 (d).
Fig. 4 is SEM images of ibuprofen intercalated magnesium aluminum hydrotalcite sustained release materials prepared in example 1, example 2, example 3 and example 4, which are respectively shown in fig. 4 (a), fig. 4 (b), fig. 4 (c) and fig. 4 (d).
Fig. 5 shows the release performance of the ibuprofen intercalated magnesium aluminum hydrotalcite sustained release materials prepared in example 1, example 2, example 3 and example 4 in different pH environments.
Fig. 6 is a TG diagram of the magnesium aluminum hydrotalcite prepared in example 1, example 2, example 3, and example 4.
Detailed Description
The invention mainly aims at the problems that the water solubility of the non-steroidal anti-inflammatory, antipyretic and analgesic ibuprofen is poor, the half-life period is short, and the clinical application of the ibuprofen is influenced, and provides a preparation method of an ibuprofen intercalation magnalium hydrotalcite sustained-release material, which realizes the controlled release of the molecular level of the ibuprofen, reduces the toxic and side effects and burst release of the ibuprofen, improves the bioavailability of the ibuprofen intercalation magnalium hydrotalcite sustained-release material, and obtains the ibuprofen intercalation magnalium hydrotalcite sustained-release material.
The ibuprofen intercalation magnalium hydrotalcite sustained-release material is mainly characterized in that: the space between the material layers of the ibuprofen intercalation magnalium hydrotalcite sustained-release material is further enlarged, the ibuprofen is successfully inserted between the hydrotalcite laminates in a-COO-ion form and forms hydrogen bonds with hydroxyl on the laminates, the combination is good, the sustained-release performance is excellent, and the ibuprofen intercalation magnalium hydrotalcite sustained-release material can be used in the field of drug carriers.
The following examples are given to further illustrate the invention. It should be noted that the following examples are not to be construed as limiting the scope of the invention, which is intended to be covered by the claims if any insubstantial modifications or adaptations of the invention in light of the above teachings.
The chemicals used in the examples are all commercially available.
Example 1
The preparation method of the ibuprofen intercalated magnesium aluminum hydrotalcite sustained-release material provided by the embodiment comprises the following steps:
(1) Magnesium chloride hexahydrate (0.21 mol) and sodium aluminate (0.07 mol) are weighed according to the mol ratio of 3 -1 And 100mL of a 0.4 mol/L sodium hydroxide aqueous solution -1 Heating the obtained mixed solution to 90 ℃, reacting for 30 minutes under the conditions of constant temperature and constant speed electric stirring (the stirring speed is 600 revolutions per minute), standing, cooling, performing suction filtration, washing the obtained product with deionized water, drying for 6 hours at 60 ℃, and grinding to obtain the magnesium-aluminum hydrotalcite (marked as T) with the particle size of 500-1000 nm 1 )。
(2) Putting the magnalium hydrotalcite prepared in the step (1) into a crucible, then transferring the crucible into a tubular furnace, introducing nitrogen for protection, heating the tubular furnace from room temperature to 500 ℃ under the condition that the heating rate is 5 ℃/min, and preserving heat for 3 hours to obtain calcined hydrotalcite (marked as T) 1 -D)。
(3) Adding the calcined hydrotalcite into an ibuprofen ethanol solution with the mass fraction of 0.5%, wherein the mass ratio of the calcined hydrotalcite to the ibuprofen is 100:30, fully stirring to form a suspension, adjusting the pH value of the obtained suspension to 5, heating to 70 ℃, reacting at a constant temperature for 5 hours, filtering after the reaction is finished, drying the obtained product in vacuum for 24 hours at the temperature of 60 ℃, and grinding to obtain the ibuprofen intercalation magnalium hydrotalcite slow-release material (marked as T) 1 -B)。
Example 2
The ibuprofen intercalation magnalium hydrotalcite sustained-release material provided by the embodiment has the preparation method that:
(1) According to a molar ratio of3, weighing magnesium chloride hexahydrate (0.21 mol) and sodium aluminate (0.07 mol) to be respectively dissolved in 100mL of deionized water, mixing the two solutions, putting the mixture into a three-neck flask, and sequentially adding 100mL of 5.5 mol.L -1 And 100mL of a 0.3 mol/L sodium hydroxide aqueous solution -1 Heating the obtained mixed solution to 90 ℃, reacting for 120 minutes under constant temperature and constant speed electric stirring (stirring speed is 500 r/min), standing, cooling, filtering, washing the obtained product with deionized water, drying for 4 hours at 60 ℃, and grinding to obtain the magnesium-aluminum hydrotalcite (marked as T) with the particle size of 500-1000 nm 2 )。
(2) Putting the magnalium hydrotalcite prepared in the step (1) into a crucible, then transferring the crucible into a tubular furnace, introducing nitrogen for protection, heating the tubular furnace from room temperature to 500 ℃ under the condition that the heating rate is 5 ℃/min, and preserving heat for 3 hours to obtain calcined hydrotalcite (marked as T) 2 -D)
(3) Adding the calcined hydrotalcite obtained in the step (2) into an ibuprofen ethanol solution with the mass fraction of 0.5%, wherein the mass ratio of the calcined hydrotalcite to the ibuprofen is 100 2 -B)。
Example 3
The preparation method of the ibuprofen intercalated magnesium aluminum hydrotalcite sustained-release material provided by the embodiment comprises the following steps:
(1) Magnesium chloride hexahydrate (0.21 mol) and sodium aluminate (0.07 mol) are weighed according to the mol ratio of 3 -1 And 100mL of a 0.3 mol/L sodium hydroxide aqueous solution -1 Heating the obtained mixed solution to 100 ℃, stirring at a constant temperature and a constant speed by an electric motor at a stirring speed of 400 r/min, reacting for 30 min, standing, cooling, performing suction filtration, washing the obtained product with deionized water, drying at 60 ℃ for 5 h, and grinding to obtain the sodium carbonate aqueous solutionMagnesium-aluminum hydrotalcite (marked as T) with particle size of 500-1000 nm 3 )。
(2) Putting the magnalium hydrotalcite prepared in the step (1) into a crucible, then transferring the crucible into a tubular furnace, introducing nitrogen for protection, heating the tubular furnace from room temperature to 500 ℃ at the heating rate of 5 ℃/min, and preserving heat for 3 hours to obtain calcined hydrotalcite (marked as T) 3 -D)。
(3) Adding the calcined hydrotalcite obtained in the step (2) into an ibuprofen ethanol solution with the mass fraction of 0.5%, wherein the mass ratio of the calcined hydrotalcite to the ibuprofen is 100 3 -B)。
Example 4
The ibuprofen intercalation magnalium hydrotalcite sustained-release material provided by the embodiment has the preparation method that:
(1) Weighing magnesium chloride hexahydrate (0.21 mol) and sodium aluminate (0.07 mol) according to the mol ratio of 3 -1 And 100mL of a 0.4 mol/L sodium hydroxide aqueous solution -1 Heating the obtained mixed solution to 100 ℃, stirring at a constant temperature and a constant speed by an electric motor at the stirring speed of 700 r/min, reacting for 120min, standing, cooling, performing suction filtration, washing the obtained product with deionized water, drying at the temperature of 60 ℃, and grinding to obtain the magnesium-aluminum hydrotalcite (marked as T) with the particle size of 500-1000 nm 4 )。
(2) Putting the magnesium-aluminum hydrotalcite prepared in the step (1) into a crucible, transferring the crucible into a tubular furnace, introducing nitrogen for protection, heating the tubular furnace from room temperature to 500 ℃ at the heating rate of 5 ℃/min, and preserving the heat for 3 hours to obtain calcined hydrotalcite (marked as T) 4 -D)。
(3) Adding the calcined hydrotalcite obtained in the step (2) into 0.5 mass percent ibuprofen, adding the ibuprofen into an ethanol solution, and calcining the hydrotalcite and the ibuprofenAnd (2) fully stirring the ibuprofen with the mass ratio of 100 to 10 to form a suspension, adjusting the pH of the obtained suspension to 6, heating the suspension to 70 ℃, reacting at a constant temperature for 5 hours, after the reaction is finished, performing suction filtration, performing vacuum drying on the obtained product at the temperature of 60 ℃ for 24 hours, and grinding to obtain the ibuprofen intercalation magnalium hydrotalcite sustained-release material (marked as T) 4 -B)。
The magnesium-aluminum hydrotalcite and the calcined hydrotalcite prepared in examples 1 to 4 were subjected to XRD tests, respectively. As can be seen from fig. 1, diffraction peaks of the magnesium-aluminum hydrotalcites prepared in examples 1, 2, 3 and 4 are strong and sharp, have high symmetry and good crystallinity, and characteristic diffraction peaks respectively appear at 11.3, 22.7, 34.3, 38.5, 45.4 and 60.2 ° of 2 θ, which indicates that the prepared products are the magnesium-aluminum hydrotalcites, wherein 11.3, 22.7 and 34.3 ° respectively correspond to (003), (006) and (009) crystal plane diffraction peaks of the magnesium-aluminum hydrotalcites, and the three characteristic peaks have good power relations, indicating that the magnesium-aluminum hydrotalcites have good layered structures, and 60.2 ° corresponds to (110) crystal plane diffraction peaks of the hydrotalcites, wherein d (003) and 2d (110) respectively represent the interlayer spacing of the magnesium-aluminum hydrotalcites and the distance between Mg and Al atoms in the crystal plane structures. In addition, the reaction time was prolonged as calculated by the bragg equation, and the interlayer spacing of example 1 was increased from d (003) =0.784nm to 0.817nm of example 2. The interlayer spacing of example 3 was increased from d (003) =0.791 to 0.822nm of example 4, and it can be seen that the interlayer spacing gradually increased with increasing temperature, showing a good layered structure.
As can be seen from FIG. 1, the characteristic peaks of the hydrotalcite after high-temperature calcination are obviously reduced and the interlayer spacing is widened compared with that before calcination, and obvious MgO and Al appear at the 2 theta positions of 37.1, 42.9, 62.5 and 78.7 degrees 2 O 3 Characteristic diffraction peaks, forming a bimetallic mixed oxide, wherein Al 2 O 3 The main amorphous form is favorable for loading the drug.
The invention also carries out XRD test on the ibuprofen intercalation magnalium hydrotalcite sustained release material prepared in the embodiment 1-4. Fig. 2 is an XRD comparison graph of ibuprofen intercalated magnesium aluminum hydrotalcite sustained release material prepared in example 1, example 2, example 3 and example 4. As can be seen from fig. 2, the XRD patterns of the ibuprofen intercalated magnesium-aluminum hydrotalcite sustained-release materials prepared in example 1, example 2, example 3 and example 4 respectively show characteristic diffraction peaks of hydrotalcite at about 11.3, 22.7, 34.3, 38.5, 45.4 and 60.2 ° 2 θ, because the calcined product of hydrotalcite can recover its layered structure by adsorbing ions, which is an embodiment of "memory function" of hydrotalcite and is also a reason that calcined hydrotalcite has high load-carrying performance. The characteristic peak of the hydrotalcite is found to shift towards a low angle, and the d (003) of the ibuprofen intercalation magnalium hydrotalcite is calculated by a Bragg equation to be increased to 2.581-2.594 nm which is larger than the interlayer spacing of 0.822nm of the magnalium hydrotalcite, which indicates that the ibuprofen molecules are successfully intercalated and calcined the magnalium hydrotalcite, and the increase of the interlayer spacing is beneficial to medicine loading.
The invention further performs SEM test on the magnesium-aluminum hydrotalcite and ibuprofen intercalation magnesium-aluminum hydrotalcite sustained-release material prepared in the embodiment 1-4.
Fig. 3 is SEM images of magnesium aluminum hydrotalcite prepared in example 1, example 2, example 3, and example 4, and respectively shows fig. 3 (a), fig. 3 (b), fig. 3 (c), and fig. 3 (d). As can be seen from fig. 3, the magnesium-aluminum hydrotalcite prepared in example 1 has a small amount of lamellar structure, and because the reaction is incomplete, the crystal grain is small, the crystal grain is not good in development, a regular lamellar structure cannot be seen, and the crystal contour is unclear; the crystal grains of the magnesium aluminum hydrotalcite prepared in example 2 are increased. The crystal grains of the magnesium-aluminum hydrotalcite prepared in the embodiment 3 are in a regular flaky structure, and obvious laminate stacking is realized; the magnalium hydrotalcite prepared in example 4 has more regular flaky grains and is uniformly distributed.
Fig. 4 is SEM images of ibuprofen intercalated magnesium aluminum hydrotalcite sustained release materials prepared in example 1, example 2, example 3 and example 4, which are respectively shown in fig. 4 (a), fig. 4 (b), fig. 4 (c) and fig. 4 (d). From the SEM images of the ibuprofen intercalated magnesium aluminum hydrotalcite sustained release materials prepared in example 1, example 2, example 3, and example 4, it can be seen that ibuprofen has entered the interlayer of calcined hydrotalcite, and is well combined with calcined hydrotalcite and distributed uniformly.
The invention tests the drug release performance of the ibuprofen intercalation magnalium hydrotalcite sustained release material prepared in the embodiment 1-4. The method for testing the drug release performance comprises the following steps: will be weighed0.1g of the adsorbed ibuprofen intercalated magnesium aluminum hydrotalcite sustained-release material is put into a dialysis small bag, and is immersed into 100mL of buffer solution, the dialysis is carried out in a constant temperature oscillator at 37 ℃ at 100r/min, samples are taken at regular intervals, and the original solution is completely replaced by 100mL of fresh buffer solution. Measuring the absorbance of the released solution at 264nm by using an ultraviolet spectrophotometer to determine the cumulative drug release percentage of the ibuprofen, wherein the specific calculation formula is as follows: cumulant release = R t /R i Wherein R is t The amount of drug released at time t; r is i Is the total amount of drug loaded into the composite material. The drug release performance of the ibuprofen intercalation magnalium hydrotalcite sustained release material under different pH conditions is respectively tested.
Fig. 5 is a graph of the test results of the drug release performance of the ibuprofen intercalated magnesium aluminum hydrotalcite sustained release materials prepared in example 1, example 2, example 3 and example 4 in different pH environments. As can be seen from fig. 5, in the environment with pH 2.0 (simulated gastric juice environment), the ibuprofen intercalation magnalium hydrotalcite sustained release material prepared in example 1, example 2, example 3 and example 4 has higher cumulative release rate of ibuprofen than the environment with pH 7.4 (simulated intestinal environment), and has burst release phenomenon. This is because, under acidic conditions, the inorganic layer of hydrotalcite gradually dissolves and undergoes ion exchange, causing the interlayer drug molecules to be suddenly released; under alkaline conditions, the layered plates of the hydrotalcite are stable and not easy to dissolve, and the drug release is mainly diffusion.
TABLE 1 comparison of the results of the maximum drug loading test for the magnesium aluminum hydrotalcite and calcined magnesium aluminum hydrotalcite prepared in the examples
Wherein:
the maximum drug loading calculation method of the magnesium-aluminum hydrotalcite comprises the following steps: the maximum mass of the drug loaded with the magnesium-aluminum hydrotalcite/the mass of the magnesium-aluminum hydrotalcite is 100 percent;
the method for calculating the maximum drug loading of the calcined magnesium-aluminum hydrotalcite comprises the following steps: maximum mass of drug loaded in calcined magnesium aluminum hydrotalcite/mass of calcined magnesium aluminum hydrotalcite 100%.
Fig. 6 is a TG diagram of the magnesium aluminum hydrotalcite prepared in example 1, example 2, example 3, and example 4. As can be seen from fig. 6, with the increase of the reaction time, the thermal decomposition temperature of the magnesium-aluminum hydrotalcite obviously moves to a high temperature, and when the temperature is 120 ℃, the mass loss rate in the second weight loss stage is relatively large, which indicates that the magnesium-aluminum hydrotalcite has relatively large interlayer spacing and can accommodate more water molecules, the residual rate of all samples at 1000 ℃ is about 49.0%, and according to the element composition of the hydrotalcite, it indicates that all the calcined products are Mg and Al oxides after dehydration and decomposition in the high temperature process.
Claims (8)
1. A preparation method of ibuprofen intercalation magnalium hydrotalcite sustained-release material is characterized in that: the method specifically comprises the following steps:
(1) Weighing soluble magnesium salt and sodium aluminate in sequence according to the proportion, then respectively dissolving the soluble magnesium salt and the sodium aluminate in deionized water to obtain a magnesium salt aqueous solution and a sodium aluminate aqueous solution, and then uniformly mixing the magnesium salt aqueous solution and the sodium aluminate aqueous solution to obtain a mixed solution 1;
(2) Adding an alkaline precipitator and soluble carbonate into the mixed solution 1 obtained in the step (1), uniformly mixing to obtain a mixed solution 2, heating the mixed solution 2 to 90-100 ℃, stirring at a constant temperature and a constant speed at the temperature of 90-100 ℃ for reaction for 30-120 minutes, standing and cooling after the reaction is finished, carrying out suction filtration, washing, drying and grinding on the obtained product to obtain the magnalium hydrotalcite;
(3) Putting the magnesium-aluminum hydrotalcite obtained in the step (2) into a crucible, then transferring the crucible into a tubular furnace, introducing nitrogen for protection, heating the tubular furnace from room temperature to 500 ℃, and carrying out heat preservation and calcination for 3 hours at 500 ℃ under the protection of nitrogen atmosphere to obtain calcined hydrotalcite;
(4) And (3) adding the calcined hydrotalcite obtained in the step (3) into an ethanol solution of ibuprofen according to a ratio, fully stirring to form a suspension, adjusting the pH of the obtained suspension to 5-6, heating to 60-80 ℃, reacting at a constant temperature for 4-6 hours, after the reaction is finished, performing suction filtration, vacuum drying and grinding to obtain the ibuprofen intercalation magnalium hydrotalcite slow-release material.
2. The preparation method of the ibuprofen intercalated magnesium aluminum hydrotalcite sustained-release material according to claim 1, which is characterized in that: the molar ratio of the soluble magnesium salt to the sodium aluminate in the step (1) is 2-4.
3. The preparation method of the ibuprofen intercalated magnesium aluminum hydrotalcite sustained-release material according to claim 1, which is characterized in that: the molar ratio of the alkaline precipitant, the soluble carbonate and the soluble magnesium salt in the step (2) is (0.2-1): (0.025-0.2): (0.2-0.25).
4. The preparation method of the ibuprofen intercalated magnesium aluminum hydrotalcite sustained-release material according to claim 1, which is characterized in that: the alkaline precipitator in the step (2) is any one of sodium hydroxide, potassium hydroxide and calcium hydroxide; the soluble carbonate is any one of sodium carbonate, potassium carbonate, ammonium carbonate or ammonium bicarbonate.
5. The preparation method of the ibuprofen intercalated magnesium aluminum hydrotalcite sustained-release material according to claim 1, which is characterized in that: the temperature rise rate of the tube furnace in the step (3) is 1-10 ℃/min.
6. The preparation method of the ibuprofen intercalated magnesium aluminum hydrotalcite sustained-release material according to claim 1, which is characterized in that: the mass fraction of the ibuprofen in the ethanol solution of the ibuprofen in the step (4) is 0.5-1.0%.
7. The preparation method of the ibuprofen intercalated magnesium aluminum hydrotalcite sustained-release material according to claim 1, which is characterized in that: the dosage ratio of the calcined hydrotalcite to the ibuprofen in the step (4) is 100.
8. The ibuprofen intercalated magnesium aluminum hydrotalcite sustained release material prepared by the preparation method of the ibuprofen intercalated magnesium aluminum hydrotalcite sustained release material of any one of claims 1 to 7.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202010657186.3A CN111744017B (en) | 2020-07-09 | 2020-07-09 | Ibuprofen intercalation magnalium hydrotalcite sustained-release material and preparation method thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202010657186.3A CN111744017B (en) | 2020-07-09 | 2020-07-09 | Ibuprofen intercalation magnalium hydrotalcite sustained-release material and preparation method thereof |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN111744017A CN111744017A (en) | 2020-10-09 |
| CN111744017B true CN111744017B (en) | 2023-02-28 |
Family
ID=72710091
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202010657186.3A Active CN111744017B (en) | 2020-07-09 | 2020-07-09 | Ibuprofen intercalation magnalium hydrotalcite sustained-release material and preparation method thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN111744017B (en) |
Families Citing this family (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN113716888B (en) * | 2021-08-13 | 2022-11-18 | 广西大学 | Preparation method of hydrotalcite rust inhibitor based on single-point pH value control |
| CN113620326A (en) * | 2021-08-20 | 2021-11-09 | 云南创能斐源金属燃料电池有限公司 | Method for preparing magnesium-aluminum-zinc hydrotalcite from aluminum-air battery electrolysis waste liquid and application thereof |
| CN115989816A (en) * | 2023-02-14 | 2023-04-21 | 中国农业科学院农业环境与可持续发展研究所 | Hymexazol intercalated hydrotalcite nano bactericide and preparation method and application thereof |
| CN116196222A (en) * | 2023-02-28 | 2023-06-02 | 上海沐良医疗器械有限公司 | Caries preventing additive, caries preventing material, dental diaphragm and invisible appliance |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101112374A (en) * | 2007-06-20 | 2008-01-30 | 山东大学 | Camptothecinum-layered thermometal hydroxide nanometer complexes and method for preparing the same |
| CN101507819A (en) * | 2009-03-27 | 2009-08-19 | 北京化工大学 | Large-grainsize medicine intercalated hydrotalcite and preparation method thereof |
| CN102423490A (en) * | 2011-11-21 | 2012-04-25 | 山东大学 | Nano-hybrid of brufen and hydrotalcite-like and preparation method thereof |
-
2020
- 2020-07-09 CN CN202010657186.3A patent/CN111744017B/en active Active
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101112374A (en) * | 2007-06-20 | 2008-01-30 | 山东大学 | Camptothecinum-layered thermometal hydroxide nanometer complexes and method for preparing the same |
| CN101507819A (en) * | 2009-03-27 | 2009-08-19 | 北京化工大学 | Large-grainsize medicine intercalated hydrotalcite and preparation method thereof |
| CN102423490A (en) * | 2011-11-21 | 2012-04-25 | 山东大学 | Nano-hybrid of brufen and hydrotalcite-like and preparation method thereof |
Non-Patent Citations (2)
| Title |
|---|
| 《反应时间对镁铝水滑石结构的影响》;胡盛;《非金属矿》;20190131;第40-43页 * |
| 《牛磺酸和布洛芬插层MgAl-LDHs药物缓释材料制备及其结构研究》;谢襄漓;《矿物学报》;20121231;第481-485页 * |
Also Published As
| Publication number | Publication date |
|---|---|
| CN111744017A (en) | 2020-10-09 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN111744017B (en) | Ibuprofen intercalation magnalium hydrotalcite sustained-release material and preparation method thereof | |
| CN104378981B (en) | MOF synthesis | |
| CN1252075C (en) | Complex ML(DCA) of copper(II), gallium(III) and rare earth ion(Ln**) containing non-methyl canthridic acid radical | |
| Mondal et al. | MgAl-layered double hydroxide nanoparticles for controlled release of salicylate | |
| Niu et al. | Controlled synthesis of luminescent F-substituted strontium hydroxyapatite with hierarchical structures for drug delivery | |
| WO2006061685A1 (en) | A cost-effective process for preparation of manufacture of iron sucrose | |
| EP2429950B1 (en) | Process for the preparation of lanthanum carbonate dihydrate | |
| Haraketi et al. | Intercalation behavior of salicylic acid into calcined Cu-Al-layered double hydroxides for a controlled release formulation | |
| CN104528799A (en) | Preparation method of ultrafine magnesium-based rare earth hexaaluminate powder | |
| KR20140066756A (en) | Pharmaceutically active phosphate binders, their manufacture, compositions containing them and their use | |
| CN102631685B (en) | Coprecipitation method for preparing methotrexate/ layered double hydroxides nanocomposite material | |
| Luo et al. | A single-ligand-protected Eu 60− n Gd (Tb) n cluster: a reasonable new approach to expand lanthanide aggregations | |
| CN104108737A (en) | Synthetic method of copper-rare earth nano petal-shaped metal oxide | |
| CN111825111A (en) | Preparation method for improving thermal stability of magnesium-aluminum hydrotalcite | |
| CN111517658A (en) | Method for preparing mesoporous bioglass powder with different compositions and controllable morphology | |
| KR100536957B1 (en) | Honeycomb-shaped ion-exchange type lithium manganese oxide adsorbent and method for preparing the same | |
| CN101785860A (en) | Tegafur/layered duplex metal hydroxide nanometer hybrid and preparation method thereof | |
| JPS63280100A (en) | Crystalline human proinsulin and manufacture | |
| MX2015004188A (en) | Layered double hydroxides. | |
| CN100998872A (en) | Polypeptide medicine intercalation hydrotalcite and its preparation method | |
| CN110745849B (en) | Preparation method of nitrate radical intercalated magnalium hydrotalcite | |
| CN101530621A (en) | Oxidation resisting dipeptide medicament intercalated houghite and preparation method thereof | |
| CN114620698B (en) | Large-particle zirconium phosphate and preparation method thereof | |
| CN102674384B (en) | Hydrotalcite like compound-kaolin composite material and preparation method thereof | |
| CN114162945A (en) | Meta-aluminate intercalated magnesium-iron type hydrotalcite and preparation method thereof |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant |