Pioglitazone nanoemulsion as well as preparation method and application thereof

Abstract

The invention relates to the technical field of pharmaceutical preparations, in particular to pioglitazone nanoemulsion as well as a preparation method and application thereof. According to the pioglitazone nano-emulsion disclosed by the invention, the lauric acid propylene glycol ester is used as an oil phase, the lauric acid propylene glycol ester is used as medium-chain fatty acid, and the stable nano-emulsion is formed by embedding a surfactant and penetrating into an interfacial film on the basis of not influencing the solubility of pioglitazone. The pioglitazone nano-emulsion is prepared by adopting a compounding mode of matching the main surfactant and the cosurfactant, so that the surfactants can form relatively good hydrophilic-lipophilic balance, the flexibility of the surfactant layer is enhanced, and the pioglitazone nano-emulsion can be distributed to an oil-water interface to a relatively high degree, and the stable pioglitazone nano-emulsion can be obtained more easily.

Description

Technical Field

[0001] The present invention relates to the technical field of pharmaceutical preparations, and in particular to a pioglitazone nanoemulsion and a preparation method and application thereof. Background Art

[0002] The information disclosed in this background technology section is only intended to enhance the understanding of the overall background of the invention, and should not necessarily be regarded as an admission or any form of suggestion that the information constitutes the prior art already known to a person skilled in the art.

[0003] Inflammatory skin diseases are a group of diseases caused by the destruction of skin tissue due to dysregulation of the immune system, including eczema, atopic dermatitis, psoriasis, chronic urticaria, vitiligo, pemphigus, etc. Interleukin (IL)-1α, IL-1β, IL-6, IL-8 and tumor necrosis factor α (TNF-α) are key mediators of skin inflammatory response, and reducing the excessive production of proinflammatory cytokines is an effective treatment for skin inflammation.

[0004] Pioglitazone is an oral antidiabetic drug of the thiazolidinedione class and a highly selective agonist of peroxisome proliferator-activated receptor γ (PPARγ). Pioglitazone controls blood sugar levels by increasing peripheral and hepatic insulin sensitivity. Currently, the drug is sold on the market in the form of oral tablets and is mainly used to treat type 2 diabetes. PPARγ is a ligand-activated nuclear transcription factor whose functions include regulating cell differentiation, proliferation, immune / inflammatory response, lipid metabolism, glycolysis, and insulin resistance. Pioglitazone has a regulatory effect on inflammatory markers such as IL-6, IL-17, and TNF-α, and can inhibit the production of proinflammatory factors IL-1β, IL-6, and TNF-α, indicating that pioglitazone is an effective candidate drug for controlling inflammatory diseases. However, pioglitazone is poorly soluble in water, so its bioavailability is low, which limits its application. At the same time, thiazolidinediones, including pioglitazone, have a potential risk of causing or aggravating congestive heart failure after oral administration. When using pioglitazone or increasing the dosage of the drug, the patient should be closely monitored for symptoms and signs of heart failure (including abnormally rapid weight gain, dyspnea and / or edema). Summary of the invention

[0005] In order to overcome the above problems, the present invention provides a pioglitazone nanoemulsion and a preparation method and application thereof.

[0006] In order to achieve the above technical objectives, the present invention adopts the following technical solutions:

[0007] The first aspect of the present invention provides a pioglitazone nanoemulsion, which comprises, by mass percentage:

[0008] Pioglitazone 1% to 5%; oil phase 16% to 32%; main surfactant 30% to 36%; co-surfactant 9% to 12%, the balance is water;

[0009] Among them, the oil phase is propylene glycol laurate.

[0010] The second aspect of the present invention provides a method for preparing the pioglitazone nanoemulsion according to the first aspect, comprising:

[0011] (1) mixing pioglitazone and an oil phase to obtain a first mixture;

[0012] (2) adding a primary surfactant and a co-surfactant to the first mixture in sequence, and mixing to obtain a second mixture;

[0013] (3) Adding water to the second mixture to obtain a pioglitazone nanoemulsion.

[0014] The third aspect of the present invention provides use of the pioglitazone nanoemulsion described in the first aspect and / or the pioglitazone nanoemulsion prepared by the preparation method described in the second aspect in preparing a drug for treating inflammatory skin diseases.

[0015] The fourth aspect of the present invention provides a medicine or a pharmaceutical composition for treating inflammatory skin diseases, comprising the pioglitazone nanoemulsion described in the first aspect and / or the pioglitazone nanoemulsion prepared by the preparation method described in the second aspect.

[0016] The beneficial effects of the present invention are:

[0017] (1) Nanoemulsion preparations of pioglitazone can overcome the shortcomings of poor water solubility and poor percutaneous absorption of pioglitazone and improve the skin bioavailability of pioglitazone.

[0018] (2) Compared with the current oral administration of pioglitazone, the preparation of pioglitazone nanocream, through topical administration, the active molecules are directly applied to the skin action site without entering the bloodstream, which correspondingly reduces the exposure of other organs and tissues in the body, thereby reducing systemic side effects.

[0019] (3) The present invention prepares pioglitazone nanoemulsion by emulsification method. The difficulty of preparing nanoemulsion lies in the selection and ratio of the oil phase and surfactant of nanoemulsion. In the present invention, propylene glycol laurate is selected as the oil phase by single factor method, and propylene glycol laurate is used as the medium chain fatty acid. On the basis of not affecting the solubility of pioglitazone, the surfactant is embedded and penetrated into the interface film to form a stable nanoemulsion.

[0020] (4) The pioglitazone nanoemulsion provided by the present invention is prepared by a compounding method of a main surfactant and a co-surfactant, which can make the surfactant form a better hydrophilic-lipophilic balance, enhance the flexibility of the surfactant layer, and can be distributed to the oil-water interface to a higher degree, making it easier to obtain a stable pioglitazone nanoemulsion. The surfactant compound combination obtained by the present invention through research is: polyethylene glycol-12-hydroxystearate as the main surfactant, diethylene glycol monoethyl ether and propylene glycol as co-surfactants. Furthermore, the addition of propylene glycol in the co-surfactant can affect the particle size of the nanoemulsion, and then affect the stability of the nanoemulsion. As the amount of propylene glycol added increases, the particle size of the nanoemulsion decreases, then remains unchanged, and the stability is improved; this is because the short carbon chain propylene glycol is more easily inserted into the interfacial film of the emulsifier, reduces the interfacial tension, increases the solubility of the emulsifier, and makes the emulsion form smaller droplets. BRIEF DESCRIPTION OF THE DRAWINGS

[0021] The accompanying drawings in the specification, which constitute a part of the present invention, are used to provide a further understanding of the present invention. The exemplary embodiments of the present invention and their descriptions are used to explain the present invention and do not constitute improper limitations on the present invention.

[0022] Figure 1 is the particle size distribution diagram of the pioglitazone nanoemulsion prepared in Example 1;

[0023] Figure 2 is the particle size distribution diagram of the pioglitazone nanoemulsion prepared in Example 2;

[0024] Figure 3 is the particle size distribution diagram of the pioglitazone nanoemulsion prepared in Example 5;

[0025] Figure 4 This is a microscope image of the pioglitazone nanocream (0.5wt%) prepared in Example 7. DETAILED DESCRIPTION

[0026] It should be noted that the following detailed descriptions are exemplary and are intended to provide further explanation of the present invention. Unless otherwise specified, all technical and scientific terms used in the present invention have the same meanings as those commonly understood by those skilled in the art to which the present invention belongs.

[0027] It should be noted that the terms used herein are only for describing specific embodiments and are not intended to limit exemplary embodiments according to the present invention. As used herein, unless the context clearly indicates otherwise, the singular form is also intended to include the plural form. In addition, it should be understood that when the terms "comprising" and / or "including" are used in this specification, it indicates the presence of features, steps, operations, devices, components and / or combinations thereof.

[0028] A first typical embodiment of the present invention provides a pioglitazone nanoemulsion, which comprises, by mass percentage:

[0029] Pioglitazone 1% to 5%; oil phase 16% to 32%; main surfactant 30% to 36%; co-surfactant 9% to 12%, the balance is water;

[0030] Among them, the oil phase is propylene glycol laurate.

[0031] In one or more embodiments, the primary surfactant includes polyethylene glycol-12-hydroxystearate.

[0032] In one or more embodiments, the co-surfactant is a compound surfactant, and the compound surfactant is composed of diethylene glycol monoethyl ether and propylene glycol;

[0033] Preferably, the mass ratio of diethylene glycol monoethyl ether to propylene glycol is (1-3):1, preferably 2:1.

[0034] In one or more embodiments, the particle size distribution range of the pioglitazone nanoemulsion is 80 to 150 nm.

[0035] In one or more embodiments, the pioglitazone nanoemulsion, measured by mass percentage, comprises:

[0036] Pioglitazone 1.5%; oil phase propylene glycol laurate 22%; main surfactant polyethylene glycol-12-hydroxystearate 35%; co-surfactant 9%, the balance is water;

[0037] Among them, the co-surfactant is a composite surfactant composed of diethylene glycol monoethyl ether and propylene glycol, and the mass ratio of diethylene glycol monoethyl ether to propylene glycol is 2:1.

[0038] In one or more embodiments, the pioglitazone nanoemulsion, measured by mass percentage, comprises:

[0039] Pioglitazone 1%; oil phase propylene glycol laurate 16%; main surfactant polyethylene glycol-12-hydroxystearate 30%; auxiliary surfactant 12%, the balance is water;

[0040] Among them, the co-surfactant is a composite surfactant composed of diethylene glycol monoethyl ether and propylene glycol, and the mass ratio of diethylene glycol monoethyl ether to propylene glycol is 2:1.

[0041] In one or more embodiments, the pioglitazone nanoemulsion, measured by mass percentage, comprises:

[0042] Pioglitazone 2%; oil phase propylene glycol laurate 22%; main surfactant polyethylene glycol-12-hydroxystearate 35%; auxiliary surfactant 9%, the balance is water;

[0043] Among them, the co-surfactant is a composite surfactant composed of diethylene glycol monoethyl ether and propylene glycol, and the mass ratio of diethylene glycol monoethyl ether to propylene glycol is 2:1.

[0044] In one or more embodiments, the pioglitazone nanoemulsion, measured by mass percentage, comprises:

[0045] Pioglitazone 2%; oil phase propylene glycol laurate 22%; main surfactant polyethylene glycol-12-hydroxystearate 35%; auxiliary surfactant 9%, the balance is water;

[0046] The co-surfactant is a composite surfactant composed of diethylene glycol monoethyl ether and propylene glycol, and the mass ratio of diethylene glycol monoethyl ether to propylene glycol is 1:1.

[0047] In one or more embodiments, the pioglitazone nanoemulsion, measured by mass percentage, comprises:

[0048] Pioglitazone 2%; oil phase propylene glycol laurate 22%; main surfactant polyethylene glycol-12-hydroxystearate 35%; auxiliary surfactant 9%, the balance is water;

[0049] Among them, the co-surfactant is a composite surfactant composed of diethylene glycol monoethyl ether and propylene glycol, and the mass ratio of diethylene glycol monoethyl ether to propylene glycol is 3:1.

[0050] In one or more embodiments, the pioglitazone nanoemulsion, measured by mass percentage, comprises:

[0051] Pioglitazone 3%; oil phase propylene glycol laurate 30%; main surfactant polyethylene glycol-12-hydroxystearate 32%; auxiliary surfactant 9%, the balance is water;

[0052] Among them, the co-surfactant is a composite surfactant composed of diethylene glycol monoethyl ether and propylene glycol, and the mass ratio of diethylene glycol monoethyl ether to propylene glycol is 2:1.

[0053] In one or more embodiments, the pioglitazone nanoemulsion, measured by mass percentage, comprises:

[0054] Pioglitazone 5%; oil phase propylene glycol laurate 32%; main surfactant polyethylene glycol-12-hydroxystearate 36%; auxiliary surfactant 9%, the balance is water;

[0055] Among them, the co-surfactant is a composite surfactant composed of diethylene glycol monoethyl ether and propylene glycol, and the mass ratio of diethylene glycol monoethyl ether to propylene glycol is 2:1.

[0056] A second typical embodiment of the present invention provides a method for preparing the pioglitazone nanoemulsion according to the first aspect, comprising:

[0057] (1) mixing pioglitazone and an oil phase to obtain a first mixture;

[0058] (2) adding a primary surfactant and a co-surfactant to the first mixture in sequence, and mixing to obtain a second mixture;

[0059] (3) Adding water to the second mixture to obtain a pioglitazone nanoemulsion.

[0060] In one or more embodiments, in step (1), the time for mixing pioglitazone and the oil phase is 25 to 40 minutes, preferably 30 minutes.

[0061] In one or more embodiments, in step (3), water is added dropwise to the second mixture while stirring until the system becomes thin and transparent or translucent, and then water is added dropwise to the required total amount.

[0062] The third aspect of the present invention provides use of the pioglitazone nanoemulsion described in the first aspect and / or the pioglitazone nanoemulsion prepared by the preparation method described in the second aspect in preparing a drug for treating inflammatory skin diseases.

[0063] The fourth aspect of the present invention provides a medicine or a pharmaceutical composition for treating inflammatory skin diseases, comprising the pioglitazone nanoemulsion described in the first aspect and / or the pioglitazone nanoemulsion prepared by the preparation method described in the second aspect.

[0064] In one or more embodiments, the pharmaceutical composition for treating inflammatory skin diseases includes pioglitazone nanoemulsion, which is prepared by adding pioglitazone nanoemulsion as an active ingredient to an cream base.

[0065] The route of administration of pioglitazone nanocream is topical administration.

[0066] Preferably, the cream base is composed of white vaseline, liquid paraffin, cetyl alcohol, polyethylene glycol-7-stearate, glycerin, ethylparaben and water.

[0067] In order to enable those skilled in the art to more clearly understand the technical solution of the present invention, the technical solution of the present invention will be described in detail below in conjunction with specific embodiments.

[0068] Example 1

[0069] Preparation of Pioglitazone Nanoemulsion:

[0070] The pioglitazone nanoemulsion, by mass percentage, comprises 1.5% pioglitazone, 22% oil phase, 35% main surfactant, 9% co-surfactant, and the balance is water. The specific formulation composition is shown in Table 1.

[0071] Table 1 Prescription composition

[0072] Prescription composition Weight(g) Proportion(%) Pioglitazone 1.5 1.5 Propylene glycol laurate 22 22 Polyethylene glycol-12-hydroxystearate 35 35 Diethylene glycol monoethyl ether 6 6 Propylene glycol 3 3 water 32.5 32.5

[0073] Preparation method: adding pioglitazone to propylene glycol laurate according to the ratio in Table 1, stirring for 30 minutes to obtain a first mixture; adding polyethylene glycol-12-hydroxystearate, compounded diethylene glycol monoethyl ether and propylene glycol mixture to the first mixture in sequence, stirring evenly, and mixing to obtain a second mixture; adding purified water dropwise to the second mixture while stirring, the system becomes thin and becomes transparent or translucent, and then adding water dropwise to the required total amount to obtain pioglitazone nanoemulsion.

[0074] Figure 1 is the particle size distribution diagram of the pioglitazone nanoemulsion prepared in this example, from Figure 1 It can be seen that the particle size of the pioglitazone nanoemulsion prepared in this example is 96 nm and the PDI is 0.168.

[0075] Example 2

[0076] Preparation of Pioglitazone Nanoemulsion:

[0077] The pioglitazone nanoemulsion, by mass percentage, comprises 1% pioglitazone, 16% oil phase, 30% surfactant, 12% co-surfactant, and the balance is water. The specific formulation composition is shown in Table 2.

[0078] Table 2 Prescription composition

[0079] composition Weight(g) Proportion(%) Pioglitazone 1 1 Propylene glycol laurate 16 16 Polyethylene glycol-12-hydroxystearate 30 30 Diethylene glycol monoethyl ether 8 8 Propylene glycol 4 4 water 41 41

[0080] Preparation method: Same as Example 1.

[0081] Figure 2 is the particle size distribution diagram of the pioglitazone nanoemulsion prepared in this example, from Figure 2 It can be seen that the particle size of the pioglitazone nanoemulsion prepared in this example is 77 nm and the PDI is 0.143.

[0082] Example 3

[0083] Preparation of Pioglitazone Nanoemulsion:

[0084] The pioglitazone nanoemulsion, by mass percentage, comprises 2% pioglitazone, 22% oil phase, 35% surfactant, 9% co-surfactant, and the balance is water. The specific formulation composition is shown in Table 3.

[0085] Table 3 Prescription composition

[0086] composition Weight(g) Proportion((%) Pioglitazone 2 2 Propylene glycol laurate 22 22 Polyethylene glycol-12-hydroxystearate 35 35 Diethylene glycol monoethyl ether 6 6 Propylene glycol 3 3 water 32 32

[0087] Preparation method: Same as Example 1.

[0088] Example 4

[0089] Preparation of Pioglitazone Nanoemulsion:

[0090] The pioglitazone nanoemulsion, by mass percentage, comprises 2% pioglitazone, 22% oil phase, 35% surfactant, 9% co-surfactant, and the balance is water. The specific formulation composition is shown in Table 3.

[0091] Table 4 Prescription composition

[0092] Prescription composition Weight(g) Proportion(%) Pioglitazone 1.5 1.5 Propylene glycol laurate 22 22 Polyethylene glycol-12-hydroxystearate 35 35 Diethylene glycol monoethyl ether 4.5 4.5 Propylene glycol 4.5 4.5 water 32.5 32.5

[0093] Preparation method: Same as Example 1.

[0094] Example 5

[0095] Preparation of Pioglitazone Nanoemulsion:

[0096] The pioglitazone nanoemulsion, by mass percentage, comprises 2% pioglitazone, 22% oil phase, 35% surfactant, 9% co-surfactant, and the balance is water. The specific formulation composition is shown in Table 5.

[0097] Table 5 Prescription composition

[0098] composition Weight(g) Proportion(%) Pioglitazone 1.5 1.5 Propylene glycol laurate 22 22 Polyethylene glycol-12-hydroxystearate 35 35 Diethylene glycol monoethyl ether 6.8 6.8 Propylene glycol 2.2 2.2 water 32.5 32.5

[0099] Preparation method: Same as Example 1.

[0100] Example 6

[0101] Preparation of Pioglitazone Nanoemulsion:

[0102] The pioglitazone nanoemulsion, by mass percentage, comprises 3% pioglitazone, 30% oil phase, 32% surfactant, 9% co-surfactant, and the balance is water. The specific formulation composition is shown in Table 6.

[0103] Table 6 Prescription composition

[0104] composition Weight(g) Proportion(%) Pioglitazone 3 3 Propylene glycol laurate 30 30 Polyethylene glycol-12-hydroxystearate 32 32 Diethylene glycol monoethyl ether 6 6 Propylene glycol 3 3 water 26 26

[0105] Preparation method: Same as Example 1.

[0106] Example 7

[0107] Preparation of Pioglitazone Nanoemulsion:

[0108] The pioglitazone nanoemulsion, by mass percentage, comprises 5% pioglitazone, 32% oil phase, 36% surfactant, 9% co-surfactant, and the balance is water. The specific formulation composition is shown in Table 7.

[0109] Table 7 Prescription composition

[0110] composition Weight(g) Proportion(%) Pioglitazone 5 5 Propylene glycol laurate 32 32 Polyethylene glycol-12-hydroxystearate 36 36 Diethylene glycol monoethyl ether 6 6 Propylene glycol 3 3 water 18 18

[0111] Preparation method: Same as Example 1.

[0112] Figure 3 is the particle size distribution diagram of the pioglitazone nanoemulsion prepared in this example, from Figure 3 It can be seen that the particle size of the pioglitazone nanoemulsion prepared in this example is 141 nm and the PDI is 0.044.

[0113] Example 8

[0114] Cream base preparation:

[0115] Weigh 76 g of white vaseline, 152 g of liquid paraffin, 152 g of cetyl alcohol, and 32 g of polyethylene glycol-7-stearate, melt and mix evenly at 80° C. as phase I; mix 55 g of glycerol, 1 g of ethylparaben and 532 g of water evenly, and heat to 60° C. as phase II; add phase II to phase I at 80° C., stir and mix at 1500 rpm for 20 min, cool to 50° C. and keep warm for later use.

[0116] Example 9

[0117] Preparation of pioglitazone nano cream (0.5wt%):

[0118] The mass ratio of the cream base to the nanoemulsion is 2: 1. Weigh 20 g of the cream base, heat to 60° C., add 10 g of the pioglitazone nanoemulsion of Example 1 to the cream base, keep stirring at 60° C., and cool to obtain a 0.5 wt % pioglitazone nanoemulsion.

[0119] Figure 4 This is a microscope image of the pioglitazone nanocream (0.5wt%) prepared in this example. Figure 4 It can be seen that the nanoemulsion droplets are spherical and evenly distributed.

[0120] Example 10

[0121] Preparation of Pioglitazone Nano Cream (1.0wt%):

[0122] The mass ratio of the cream base to the nanoemulsion is 1: 1. 10 g of the cream base was weighed, heated to 60° C., 10 g of the pioglitazone nanoemulsion of Example 3 was added to the cream base, stirred evenly at 60° C., and cooled to obtain a 1.0 wt % pioglitazone nanoemulsion.

[0123] Embodiment 11

[0124] Preparation of Pioglitazone Nano Cream (1.5wt%):

[0125] The mass ratio of the cream base to the nanoemulsion is 1: 1. Weigh 10 g of the cream base, heat to 60° C., add 10 g of the pioglitazone nanoemulsion of Example 6 to the cream base, keep stirring at 60° C., and cool to obtain a 1.5 wt % pioglitazone nanoemulsion.

[0126] Example 12

[0127] Preparation of Pioglitazone Nano Cream (2.5wt%):

[0128] The mass ratio of the cream base to the nanoemulsion is 1: 1. Weigh 10 g of the cream base, heat to 60° C., add 10 g of the pioglitazone nanoemulsion of Example 7 to the cream base, keep stirring at 60° C., and cool to obtain a 2.5 wt % pioglitazone nanoemulsion.

[0129] Comparative Example 1

[0130] Preparation of Pioglitazone Cream:

[0131] Weigh 49.5 g of cream base, heat to 60°C, add 0.5 g of pioglitazone (particle size d 0.9 value is less than 30 μm), maintained at 60° C. and stirred for 30 min, and then cooled to obtain a 1.0 wt% pioglitazone cream.

[0132] Example 13

[0133] Pioglitazone nanoemulsion stability test:

[0134] (1) Centrifugal stability: 5 mL of the nanoemulsion sample prepared in the example was measured and added to a 10 mL centrifuge tube, which was placed in a high-speed centrifuge and centrifuged at 5000 rpm for 15 min to observe whether the sample was separated into layers and whether there was precipitation at the bottom.

[0135] (2) Stability in hot and cold cycles: 5 mL of the nanoemulsion sample prepared in the example was measured and added to a 10 mL transparent sample tube for hot and cold environment placement study. First, it was placed in a constant temperature box (40°C) for 30 min, and then it was taken out and placed in a refrigerator (4°C) for 30 min. This was considered a cycle, and a total of 8 cycles were repeated to observe whether there was precipitation at the bottom of the sample tube or whether the sample in the sample tube was stratified.

[0136] The results are shown in Table 8.

[0137] Table 8 Pioglitazone nanoemulsion stability test results

[0138]

[0139] Embodiment 14

[0140] Study on the stability of pioglitazone nano cream:

[0141] The nanoemulsion obtained in Example 1 and the nanoemulsion samples obtained in Examples 9, 10 and 11 were subjected to the stability test shown in Table 9. The results are shown in Table 9.

[0142] Table 9 Pioglitazone nano cream stability study results

[0143]

[0144] It can be seen from Table 9 that the nanoemulsions obtained in Examples 9, 10 and 11 have higher stability than the nanoemulsion prepared in Example 1.

[0145] Embodiment 15

[0146] Determination of the anti-inflammatory efficacy of pioglitazone nanocream:

[0147] Mouse auricle swelling method: Using the self-control method (right ear induced inflammation, left ear as self-control), xylene was applied to the front and back surfaces of the right ear of the mouse to induce inflammation. After 15 minutes, the drug was evenly applied to each group, with an application amount of about 0.5 g / cm 2 The mice were killed 1.5 hours later, and circular ear pieces of the same diameter were punched in the same part of the left and right ears of the mice with a puncher, and the weights were measured to calculate the swelling degree (right ear weight minus left ear weight). The results of the anti-inflammatory efficacy test are shown in Table 10.

[0148] Table 10 Anti-inflammatory efficacy test results

[0149]

[0150] The results showed that the auricle swelling in the pioglitazone nanocream and mupirocin ointment groups was significantly lower than that in the control group (untreated) and the blank cream matrix group, but the anti-inflammatory efficacy of pioglitazone nanocream was slightly lower than that of mupirocin ointment.

[0151] Example 16

[0152] In vitro skin permeation test of pioglitazone nanocream:

[0153] The in vitro permeation test was conducted using 1-month-old Bama Xiang pig skin to compare the transdermal absorbability of the pioglitazone nanoemulsion of Example 10 and the pioglitazone cream of Comparative Example 1. The test was conducted on an Andisso 12-position transdermal diffusion instrument, the in vitro receptor solution was diethylene glycol monoethyl ether: water (60:40, v / v), the temperature was 32±0.5°C, and the pig skin area was about 1.77 cm 2 The amount of sample to be tested was 300 mg, and the amount of pioglitazone in the receiving solution was detected by HPLC. The results are shown in Table 11.

[0154] Table 11 Pioglitazone nano cream in vitro transdermal test results

[0155]

[0156] The results showed that the skin permeability of pioglitazone nanoemulsion was significantly higher than that of the control pioglitazone cream.

[0157] The above description is only a preferred embodiment of the present invention and is not intended to limit the present invention. For those skilled in the art, the present invention may have various modifications and variations. 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 pioglitazone nanoemulsion, characterized in that: In terms of mass percentage, it includes: Pioglitazone 1% to 5%; oil phase 16% to 32%; main surfactant 30% to 36%; co-surfactant 9% to 12%, the balance is water; Among them, the oil phase is propylene glycol laurate.

2. The pioglitazone nanoemulsion according to claim 1, characterized in that The particle size distribution range of the pioglitazone nanoemulsion is 80 to 150 nm; The primary surfactant includes polyethylene glycol-12-hydroxystearate.

3. The pioglitazone nanoemulsion according to claim 1, characterized in that The co-surfactant is a composite surfactant, and the composite surfactant includes diethylene glycol monoethyl ether and propylene glycol; The mass ratio of diethylene glycol monoethyl ether to propylene glycol is (1-3):

1.

4. The pioglitazone nanoemulsion according to claim 1, characterized in that Pioglitazone nanoemulsion, measured by weight percentage, comprises: Pioglitazone 1.5%; oil phase propylene glycol laurate 22%; main surfactant polyethylene glycol-12-hydroxystearate 35%; co-surfactant 9%, the balance is water; wherein the co-surfactant is a composite surfactant composed of diethylene glycol monoethyl ether and propylene glycol, and the mass ratio of diethylene glycol monoethyl ether to propylene glycol is 2:1; Pioglitazone 1%; oil phase propylene glycol laurate 16%; main surfactant polyethylene glycol-12-hydroxystearate 30%; co-surfactant 12%, the balance is water; wherein the co-surfactant is a composite surfactant composed of diethylene glycol monoethyl ether and propylene glycol, and the mass ratio of diethylene glycol monoethyl ether to propylene glycol is 2:1; Pioglitazone 2%; oil phase propylene glycol laurate 22%; main surfactant polyethylene glycol-12-hydroxystearate 35%; co-surfactant 9%, the balance is water; wherein the co-surfactant is a composite surfactant composed of diethylene glycol monoethyl ether and propylene glycol, and the mass ratio of diethylene glycol monoethyl ether to propylene glycol is 2:1; Pioglitazone 3%; oil phase propylene glycol laurate 30%; main surfactant polyethylene glycol-12-hydroxystearate 32%; co-surfactant 9%, the balance is water; wherein the co-surfactant is a composite surfactant composed of diethylene glycol monoethyl ether and propylene glycol, and the mass ratio of diethylene glycol monoethyl ether to propylene glycol is 2:1; Pioglitazone 5%; oil phase propylene glycol laurate 32%; main surfactant polyethylene glycol-12-hydroxystearate 36%; co-surfactant 9%, the balance is water; wherein the co-surfactant is a composite surfactant composed of diethylene glycol monoethyl ether and propylene glycol, and the mass ratio of diethylene glycol monoethyl ether to propylene glycol is 2:1; The particle size distribution range of the pioglitazone nanoemulsion is 80-150 nm.

5. The method for preparing the pioglitazone nanoemulsion according to any one of claims 1 to 4, characterized in that: include: (1) mixing pioglitazone and an oil phase to obtain a first mixture; (2) adding a primary surfactant and a co-surfactant to the first mixture in sequence, and mixing to obtain a second mixture; (3) Adding water to the second mixture to obtain a pioglitazone nanoemulsion.

6. The preparation method according to claim 5, characterized in that: In step (1), the time for mixing pioglitazone and the oil phase is 25 to 40 minutes; In step (3), water is added dropwise to the second mixture while stirring until the system becomes thin and transparent or translucent, and then water is added dropwise to the required total amount.

7. Use of the pioglitazone nanoemulsion according to any one of claims 1 to 4 and / or the pioglitazone nanoemulsion prepared by the preparation method according to claim 5 or 6 in the preparation of a medicament for treating inflammatory skin diseases.

8. A drug or pharmaceutical composition for treating inflammatory skin diseases, characterized in that: The invention comprises the pioglitazone nanoemulsion according to any one of claims 1 to 4 and / or the pioglitazone nanoemulsion prepared by the preparation method according to claim 5 or 6.

9. The drug or pharmaceutical composition according to claim 8, characterized in that The pharmaceutical composition for treating inflammatory skin diseases comprises pioglitazone nanoemulsion, which is prepared by taking pioglitazone nanoemulsion as an active ingredient and adding an emulsion base.

10. The drug or pharmaceutical composition according to claim 9, characterized in that The cream base is composed of white vaseline, liquid paraffin, hexadecanol, polyethylene glycol-7-stearate, glycerol, ethyl hydroxybenzoate and water.

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