Preparation method of superfine illite / minoxidil composite material

Abstract

The invention discloses a preparation method of a superfine illite / minoxidil composite material. The superfine illite / minoxidil composite material is prepared from the following raw materials in parts by weight: 1 to 5 weight percent of a surfactant, 5 to 30 weight percent of superfine illite, 1 to 10 weight percent of minoxidil and the balance of a mixed solution of ethanol and propylene glycol. Due to the nano particle size of the superfine illite, the invention relates to the technical field of medical materials and mineral composite materials, the superfine illite / minoxidil composite material provided by the invention has higher drug loading capacity, and meanwhile, due to the self-film-forming property of the superfine illite, additional addition of chemicals is avoided, so that the damage of the drug to the scalp is reduced. Besides, the method is simple, convenient and suitable for industrial large-scale production, and a new way is provided for high-added-value development of clay resources and high-performance medicine preparation.

Description

Technical Field

[0001] The invention relates to the technical field of pharmaceutical materials and mineral composite materials, and in particular to a method for preparing an ultrafine illite / minoxidil composite material. Background Art

[0002] Minoxidil is a potassium channel opener. As an effective topical agent that can promote hair growth, it has good tolerance, low incidence of adverse reactions and mild symptoms. It is currently an important drug widely used in the clinic to treat hair loss. However, minoxidil is easily oxidized, has a low transdermal absorption rate, and has high local irritation when used directly, which seriously limits its application. It needs to be sustained-released and enhanced through carrier materials to reduce skin irritation caused by direct use of the drug.

[0003] In recent years, illite has been widely used in the fields of coatings, adsorption materials, etc. due to its wide source and low price. As a natural layered silicate clay, illite has a certain specific surface area and ion exchange capacity, which can be used in the field of drug delivery. In addition, existing studies have shown that the far infrared emitted by illite matches the biological wavelength of the human body, which can promote microcirculation and metabolism, which to a certain extent increases its value in the field of topical drug delivery. Prior art CN116712567A discloses a preparation method and related applications of illite and γ-CD-MOF composite drug-carrying materials, that is, by using γ-cyclodextrin metal organic framework materials and illite clay to achieve loading of minoxidil, thereby improving the pharmacokinetic properties of the drug, improving bioavailability and reducing toxicity, and achieving controlled release. Although this method has a certain effect, the recorded illite is only obtained by a high-temperature calcination step, and its specific surface area, pore size, etc. are not enough to meet the needs of drug-carrying applications. Therefore, it is necessary to conduct in-depth research from the aspects of increasing its drug loading and controlling the release of minoxidil. Summary of the invention

[0004] In view of the above problems and practical needs of the prior art, the purpose of the present invention is to provide a method for preparing an ultrafine illite / minoxidil composite material, aiming to use experimental means to nano-crystallize illite clay to obtain ultrafine illite, and composite it with minoxidil, thereby achieving an increase in drug loading and controlling the release of minoxidil.

[0005] The present invention is achieved through the following technical solutions:

[0006] A method for preparing an ultrafine illite / minoxidil composite material. The ultrafine illite / minoxidil composite material comprises the following raw materials in parts by weight: 1-5wt% of a surfactant, 5-30wt% of ultrafine illite, 1-10wt% of minoxidil, and the remainder is a mixed solution of ethanol and propylene glycol.

[0007] The preparation process is as follows:

[0008] A. adding a surfactant to a mixed solution of ethanol and propylene glycol to obtain a solution 1;

[0009] B. minoxidil was added to solution 1 as an active ingredient, using a stirrer at a speed of 2000 ~ 4000 rpm, stirring for 10-60 min, until stirred to obtain a solution 2;

[0010] C. Ultrafine illite was added to solution 2, using a stirrer at a speed of 2000-4000 rpm, stirring for 10-60min, until stirred to obtain a solution 3;

[0011] D. Drying solution 3 to obtain a light yellow powder, which is an ultrafine illite / minoxidil composite material.

[0012] Furthermore, in step D, during the process of drying the obtained solution 3, any one of spray drying, freeze drying, and freeze spray drying can be used, and the specific conditions are:

[0013] When spray drying is used, the drying conditions are: feed rate 5-20 ml / s, inlet temperature 40-120 °C, inlet air pressure 0.1-2.0 MPa.

[0014] When freeze drying is used, the drying conditions are: freezing temperature -80°C, and freeze drying time is 3 days.

[0015] When freeze spray drying was used, the drying conditions were: feed rate 5-20 ml / s, freezing temperature -80°C, freeze drying time 1 day, and fan frequency 60 Hz.

[0016] The preparation method of the ultrafine illite is as follows:

[0017] Step 1, ball milling the natural illite and sieving it through a mesh sieve to obtain illite powder with a mesh size less than 80;

[0018] Step 2, the illite powder of step 1 is mixed with deionized water, wherein the mass concentration of illite is 10%-25% calculated by the mass ratio of illite powder to deionized water; the mixed slurry is mixed evenly using a stirrer at a stirrer speed of 1000~5000 rpm for 2 -5 h;

[0019] Step three, adding a dispersant to the mixed illite aqueous solution; wherein the mass ratio of illite powder to dispersant is 1: 0.01 ~ 0.05, and then stirring at a speed of 2000 ~ 4000 rpm, stirring for 1 ~ 2 h, so that the illite mixture is stirred evenly, and then let stand for 2 h;

[0020] Step 4: extract the upper clear liquid and the lower solid turbid liquid from the static mixed solution obtained in step 3, take the middle oily illite slurry, and make it into solid powder through a spray dryer; the reaction conditions of the spray dryer to make it into dry powder are: feed rate 5-10 ml / s, inlet temperature 110-150 ° C, and inlet air pressure 2.0 MPa.

[0021] Furthermore, the dispersant described in the above step three specifically refers to any one or a mixture of an inorganic dispersant or an organic dispersant; the inorganic dispersant is sodium hexametaphosphate, sodium chloride or sodium carbonate; the organic dispersant is sodium dodecylbenzene sulfonate or hexadecyl ammonium bromide.

[0022] Furthermore, the surfactant is one or any combination of glycerol and Tween 20, Tween 60 or Tween 80.

[0023] Furthermore, in the method for preparing the ultrafine illite / minoxidil composite material, the mass ratio of propylene glycol in the mixed solution of ethanol and propylene glycol is 1-30wt%.

[0024] Compared with the prior art, the significant beneficial effects of the present invention are as follows: ultrafine illite is used as a loading material, and since its particle size is significantly reduced, its drug loading capacity is significantly increased (the drug loading capacity can reach more than 400 mg / g), the preparation method is simple, and the conditions can meet the actual requirements of industrial-scale production, and since ultrafine illite has a certain film-forming property, the use of additional chemicals can be avoided, thereby avoiding irritation and damage to the scalp during direct application, and is also conducive to the long-term release of minoxidil. BRIEF DESCRIPTION OF THE DRAWINGS

[0025] In order to more clearly illustrate the specific implementation of the present invention or the technical solution in the prior art, the drawings required for use in the specific implementation or the description of the prior art are briefly introduced below.

[0026] Figure 1 This is a scanning electron microscope image of the illite / minoxidil composite material obtained in Example 1. In the image, the illite flake surface morphology is clear, and there is no obvious minoxidil agglomerate material, indicating that the minoxidil drug is uniformly loaded on its surface.

[0027] Figure 2 The infrared spectra of illite, minoxidil and the illite / minoxidil composite material obtained in Example 1 indicate that minoxidil is successfully loaded on the surface. DETAILED DESCRIPTION

[0028] In order to clearly and completely describe the technical solution of the present invention and its specific working process, the specific implementation methods of the present invention are as follows in conjunction with the accompanying drawings of the specification:

[0029] Example 1

[0030] A method for preparing an ultrafine illite / minoxidil composite material. The ultrafine illite / minoxidil composite material comprises the following raw materials in parts by weight: 1wt% of a surfactant, 5wt% of ultrafine illite, 1wt% of minoxidil, and the remainder is a mixed solution of ethanol and propylene glycol.

[0031] The preparation process is as follows:

[0032] Step A. adding a surfactant to a mixed solution of ethanol and propylene glycol to obtain a solution 1;

[0033] Step B. minoxidil was added to solution 1 as an active ingredient, and the mixture was stirred at a speed of 2000 rpm for 60 min until uniformly stirred to obtain a solution 2;

[0034] Step C. adding ultrafine illite to solution 2, using a stirrer at a speed of 2000 rpm, stirring for 60 min, until stirred uniformly to obtain a solution 3;

[0035] Step D: Drying the solution 3 to obtain a light yellow powder, which is the ultrafine illite / minoxidil composite material.

[0036] In step D, during the drying of the obtained solution 3, the process used is a spray drying process, and the specific conditions are: feed rate 5 ml / s, inlet temperature 40° C., and inlet air pressure 0.5 MPa.

[0037] Ultrafine illite, the preparation method is as follows:

[0038] Step 1, ball milling the natural illite and sieving it through a mesh sieve to obtain illite powder with a mesh size less than 80;

[0039] Step 2, the illite powder of step 1 is mixed with deionized water, wherein the mass concentration of illite is 25% calculated by the mass ratio of illite powder to deionized water; the mixed slurry is mixed evenly using a stirrer at a stirrer speed of 5000 rpm for 2 h;

[0040] Step three, adding a dispersant to the mixed illite aqueous solution; wherein the mass ratio of illite powder to dispersant is 1: 0.01, and then stirring at a speed of 4000 rpm with a stirrer for 2 h, so that the illite mixture is stirred evenly, and then allowed to stand for 2 h;

[0041] Step 4: extract the upper clear liquid and the lower solid turbid liquid from the static mixed solution obtained in step 3, take the middle oily illite slurry, and make it into solid powder through a spray dryer; the reaction conditions for the spray dryer to make it into powder are: feed rate 10 ml / s, inlet temperature 150°C, and inlet air pressure 0.2 MPa.

[0042] As a preferred technical solution, further, the dispersant in the above step three is specifically sodium hexametaphosphate.

[0043] As a preferred technical solution, further, 1wt% of the surfactant is a mixture of glycerol and Tween 20, and the mass ratio of glycerol to Tween 20 is 1:1.

[0044] As a preferred technical solution, further, a method for preparing an ultrafine illite / minoxidil composite material, in which the mass ratio of propylene glycol in the mixed solution of ethanol and propylene glycol is 15wt%.

[0045] The rest of Example 2 is the same as Example 1, except that the ultrafine illite / minoxidil composite material is prepared by comprising the following raw materials in parts by weight: 5wt% surfactant, 30wt% ultrafine illite, 10wt% minoxidil, and the remainder is a mixed solution of ethanol and propylene glycol.

[0046] The rest of Example 3 is the same as Example 1, except that the dispersant in step 3 is specifically sodium dodecylbenzene sulfonate.

[0047] The rest of Example 4 is the same as Example 1, except that the dispersant in step 3 is specifically hexadecyl ammonium bromide.

[0048] The rest of Example 5 is the same as Example 1, except that 5 wt % of the surfactant is a mixture of glycerol and Tween 80, and the mass ratio of glycerol to Tween 80 is 1:1.

[0049] The rest of Example 6 is the same as Example 1, except that in step D, freeze drying is used to dry the obtained solution 3, and the drying conditions are: freezing temperature -80°C and freeze drying time is 3 days.

[0050] The rest of Example 7 is the same as Example 1, except that, in the process of drying the obtained solution 3 in step D, the process used is freeze spray drying, and the drying conditions are: feed rate 20 ml / s, freezing temperature -80°C, freeze drying time is 1 day, and fan frequency is 60 Hz.

[0051] Finally, it should be noted that the above description is only a preferred embodiment of the present invention and is not intended to limit the present invention. Although the present invention has been described in detail with reference to the aforementioned embodiments, those skilled in the art can still modify the technical solutions described in the aforementioned embodiments or replace some of the technical features therein by equivalents. Any modification, equivalent replacement, improvement, etc. made within the spirit and principle of the present invention shall be included in the protection scope of the present invention.

Claims

1. A method for preparing an ultrafine illite / minoxidil composite material, characterized in that: The ultrafine illite / minoxidil composite material is prepared by comprising the following raw materials in parts by weight: 1-5wt% surfactant, 5-30wt% ultrafine illite, 1-10wt% minoxidil, and the remainder is a mixed solution of ethanol and propylene glycol, and the preparation process is as follows: Step A: adding a surfactant to a mixed solution of ethanol and propylene glycol to obtain a solution 1; Step B: adding minoxidil as an active ingredient to solution 1, stirring with a stirrer at a speed of 2000-4000 rpm for 10-60 min until the mixture is uniformly stirred to obtain solution 2; Step C: adding ultrafine illite to solution 2, stirring with a stirrer at a speed of 2000-4000 rpm for 10-60 min, and stirring until uniform, to obtain solution 3; Step D: Drying the solution 3 to obtain a light yellow powder, which is the ultrafine illite / minoxidil composite material.

2. The method for preparing an ultrafine illite / minoxidil composite material according to claim 1, characterized in that: The preparation method of the ultrafine illite is as follows: Step 1: ball milling the natural illite and sieving it through a mesh sieve to obtain illite powder with a mesh size less than 80; Step 2: mixing the illite powder obtained in step 1 with deionized water, wherein the mass concentration of the illite powder is 10%-25% calculated based on the mass ratio of the illite powder to the deionized water; Use a stirrer to mix the mixed slurry evenly, the stirrer speed is 1000~5000 rpm, and stir for 2-5 h; Step 3: adding a dispersant to the uniformly mixed illite aqueous solution; The mass ratio of illite powder to dispersant is 1:0.01-0.05, and then a stirrer is used to stir at a speed of 2000-4000 rpm for 1-2 h to make the illite mixed liquid uniformly stirred, and then it is left to stand for 2 h; Step 4: extract the upper clear liquid and the lower solid turbid liquid from the static mixed solution obtained in step 3, take the middle oily illite slurry, and make it into solid powder through a spray dryer; the reaction conditions of the spray dryer to make it into solid powder are: feed rate 5-10 ml / s, inlet temperature 110-150 ° C, and inlet air pressure 0.2 MPa.

3. The method for preparing an ultrafine illite / minoxidil composite material according to claim 1, characterized in that: In step D, the obtained solution 3 is dried by spray drying, and the drying conditions are: feed rate 5-20 ml / s, inlet temperature 40-120° C., and inlet air pressure 0.1-2.0 MPa.

4. The method for preparing an ultrafine illite / minoxidil composite material according to claim 1, characterized in that: In step D, the obtained solution 3 is dried by freeze drying, and the drying conditions are: freezing temperature -80°C, and freeze drying time is 3 days.

5. The method for preparing an ultrafine illite / minoxidil composite material according to claim 1, characterized in that: In step D, the obtained solution 3 is dried by freeze spray drying, and the drying conditions are: feed rate 5-20 ml / s, freezing temperature -80°C, freeze drying time 1 day, and fan frequency 60 Hz.

6. The method for preparing an ultrafine illite / minoxidil composite material according to claim 1, characterized in that: The surfactant is one of glycerol and Tween 20, glycerol and Tween 60 or glycerol and Tween 80.

7. The method for preparing an ultrafine illite / minoxidil composite material according to claim 1, characterized in that: In the mixed solution of ethanol and propylene glycol, the mass ratio of propylene glycol is 1-30wt%.

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