Adapalene external preparation and preparation method thereof

Abstract

The invention discloses an adapalene external preparation and a preparation method thereof, and relates to the technical field of adapalene preparation preparation. The adapalene gel comprises the following raw materials in percentage by mass: 4.5-7.5% of adapalene, 3.5-8% of a gel base material, 2-4.5% of cellulose, 0.5-2% of a penetration enhancer, 18-25% of a water-retaining agent, 2-5% of a surfactant, a pH value regulator and the balance of water, the dosage of the pH value regulator is based on the standard that the pH value of the adapalene external preparation is regulated to 7-7.5; the gel base material comprises poloxamer or carbomer, and further comprises sa-hao seed gum, and the use amount of the sa-hao seed gum accounts for 25-35% of the total mass of the gel base material. According to the adapalene external preparation provided by the invention, the irritation of adapalene to the skin is basically eliminated by utilizing the effects of the gel base material consisting of poloxamer or carbomer and sa-hao seed gum and the surfactant; the adhesive has good cohesiveness and water-retaining property, can keep the affected part moist after being smeared, promotes medicine absorption, and avoids being wiped off or automatically falling off; the stability is improved, and the medicine slow release time is indirectly prolonged.

Description

Technical Field

[0001] The present invention relates to the technical field of the preparation of adapalene preparations, and particularly relates to an adapalene topical agent and a preparation method thereof. Background Art

[0002] Adapalene, also known as 6-[3-(1-adamantyl)-4-methoxyphenyl]-2-naphthoic acid, has a molecular formula of C 28 H 28 O3. It is a white or off-white powder at room temperature, insoluble in water or ethanol, and slightly soluble in tetrahydrofuran. Adapalene is a topical dermatological drug. As a third-generation retinoid drug, it is clinically applicable to the skin treatment of acne vulgaris mainly manifested by comedones, papules, and pustules, and can also be used to treat acne on the face, chest, and back. Compared with other retinoid drugs, adapalene has stronger effects of regulating epidermal cell differentiation, inhibiting the proliferation and keratinization of keratinocytes at the hair follicle orifice, inhibiting the proliferation of sebaceous gland cells, and dissolving horn plugs and comedones. At the same time, it also has a strong anti-inflammatory effect.

[0003] Due to its acidity, adapalene has certain irritation when used on the face, which limits its clinical application; and due to its general water solubility, the stability of its topical preparations is general, and the drug transdermal diffusion efficiency is relatively low, which is not conducive to the long-term and rapid efficacy of the topical dosage form, nor is it conducive to the daily storage of the drug preparation. Summary of the Invention

[0004] Aiming at the above deficiencies of the prior art, the present invention provides an adapalene topical agent and a preparation method thereof, which are specifically realized through the following technologies.

[0005] An adapalene topical agent, the raw materials of which include 4.5-7.5% of adapalene, 3.5-8% of a gel substrate, 2-4.5% of cellulose, 0.5-2% of a penetration enhancer, 18-25% of a water-retaining agent, 2-5% of a surfactant by mass fraction, and also includes a pH regulator, and the rest is water; the dosage of the pH regulator is to adjust the pH of the adapalene topical agent to 7.5-8;

[0006] The gel substrate includes poloxamer or carbomer, and also includes artemisia sphaerocephala gum, and the dosage of the artemisia sphaerocephala gum accounts for 25-35% of the total mass of the gel substrate; the diameter of the cellulose is 5-10 nm, and the length is 2.5-10 μm.

[0007] The above-mentioned adapalene topical agent provided by the present invention is a translucent gel-like agent; its usage method is generally to apply it on the surface of the skin disease affected area, and the adapalene drug exerts its efficacy after being absorbed by the human body through the skin. Conventional gel-like agents have poor water retention and adhesiveness on the skin, are prone to dry out, and are also easily wiped off accidentally by objects such as clothes, making it difficult to ensure the efficacy of the agent. Therefore, in order to solve the above problems and improve the adhesion of the agent on the skin surface to achieve the sustained and long-term release of the adapalene drug, when selecting the gel base material, in addition to selecting poloxamer or carbomer, artemisia sphaerocephala gum is also selected. Artemisia sphaerocephala gum has good water absorption and water retention properties, and can form a stable and viscous gel-like material when encountering water, which not only ensures the water retention of the adapalene topical agent but also ensures its adhesiveness to the skin, prolongs the time when the agent is in a gel state, and ensures the long-term release of the adapalene drug.

[0008] The present invention also adds cellulose to the raw materials. As the agent material slowly loses water after being applied, cellulose can increase the roughness of the surface of the agent material, further improving the adhesiveness of the gel agent to the skin; cellulose can also slowly form a protective film layer on the surface of the agent, which not only delays the loss of water but also reduces the wiping effect of clothes, tissues, etc. on the agent. As the agent slowly and continuously loses water after being applied, the adapalene drug is also slowly absorbed by the skin until finally the agent forms a soft translucent sheet; at this time, it indicates that the effective adapalene drug has been basically absorbed by the skin and can be simply torn off by hand.

[0009] Further, the dosage of the artemisia sphaerocephala gum accounts for 32% of the total mass of the gel base material.

[0010] Further, the water retention agent is glycerol and liquid paraffin, and the mass ratio of the two is (1 - 3):1.

[0011] Further, the surfactant is at least one of Tween 80, polyoxyethylene castor oil 60, polyoxyethylene hydrogenated castor oil 60, and polyethylene glycol stearate; the penetration enhancer is at least one of lauryl alcohol, menthol, geraniol, anethole, decyl methyl sulfoxide, and sodium lauryl sulfate.

[0012] Furthermore, its raw materials include 7% of adapalene, 4% of gel base material, 3% of cellulose, 1.5% of penetration enhancer, 22% of water retention agent, 2.5% of surfactant by mass fraction, and also include a pH regulator, and the rest is water.

[0013] The present invention also provides a preparation method of the above-mentioned adapalene topical agent, which includes the following steps:

[0014] Mix the adapalene, penetration enhancer, and water retention agent evenly to obtain a first mixture;

[0015] Mix the gel substrate, cellulose and water accounting for 30 - 60% of the total water amount evenly to obtain a second mixture;

[0016] Mix the pH regulator, surfactant and the remaining water evenly to obtain a third mixture;

[0017] Mix the first mixture and the second mixture, shear, and finally add them to the third mixture for dispersion to obtain the adapalene topical preparation.

[0018] Furthermore, the conditions for shearing are shearing at 10000 - 12000 rpm for 20 - 30 min; the conditions for dispersion are dispersing at 800 - 1000 rpm for 1 - 1.5 h.

[0019] Compared with the prior art, the advantages of the present invention are as follows: The present invention provides an adapalene topical preparation. By using the gel substrate composed of poloxamer or carbomer and artemisia sphaerocephala gum and the surfactant, adapalene is embedded inside to form a microcapsule structure, basically eliminating the irritation of adapalene to the skin. The gel substrate itself also has good adhesiveness and water retention. After application, it can keep the affected area moist, promote drug absorption, and can adhere to the skin to avoid being wiped off or falling off automatically; the synergistic effect of the gel substrate and cellulose can also form a protective film on the surface of the medicament and form an interlaced fibrous microstructure inside the medicament, improving the stability of the medicament and indirectly prolonging the sustained release time of the adapalene drug. Description of the Drawings

[0020] Figure 1 It is the drug release rate curve of the adapalene topical preparations of Examples 1 - 5;

[0021] Figure 2 It is the drug release rate curve of the adapalene topical preparations of Comparative Examples 1 - 4. Detailed Embodiments

[0022] The technical solutions of the present invention will be described clearly and completely below. Obviously, the described embodiments are only a part of the embodiments of the present invention, rather than all the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those of ordinary skill in the art without creative efforts belong to the scope of protection of the present invention.

[0023] Unless otherwise specifically stated, all kinds of raw materials, reagents, instruments and equipment used in the present invention can be obtained through market purchase or can be obtained by existing methods.

[0024] The technical means disclosed in the following detailed embodiments of the present invention are to solve the above technical problems, and the general idea is as follows:

[0025] An adapalene topical agent provided by the present invention, the raw materials of which by mass fraction include 4.5-7.5% of adapalene, 3.5-8% of gel substrate, 2-4.5% of cellulose, 0.5-2% of penetration enhancer, 18-25% of water-retaining agent, 2-5% of surfactant, and also include a pH regulator, and the rest is water.

[0026] The dosage of the pH regulator is to adjust the pH of the adapalene topical agent to 7.5-8.

[0027] The gel substrate includes poloxamer or carbomer, and also includes artemisia sphaerocephala gum; and the dosage of artemisia sphaerocephala gum accounts for 25-35% of the total mass of the gel substrate. The diameter of the cellulose is 5-10 nm, and the length is 2.5-10 μm.

[0028] Both poloxamer and carbomer are commonly used commercially available gel substrates, and their specific models are not limited, and they all belong to the protection scope of the present invention. For the convenience of comparison in the following examples, poloxamer 188 is selected for all.

[0029] The above components cooperate synergistically to make the storage stability of the medicament better and the release rate more stable. Specifically:

[0030] Selecting poloxamer and artemisia sphaerocephala gum can coat the surface of adapalene nanoparticles to form nano-microcapsules, and can stably exist in the medicament after dispersion treatment with surfactants, etc., and has a good sustained-release effect after application.

[0031] Poloxamer and artemisia sphaerocephala gum have good adhesiveness, can make the medicament firmly adhere to the skin disease affected area, and prevent the medicament from being easily wiped off.

[0032] Poloxamer and artemisia sphaerocephala gum can also form a gel fiber-like structure inside the medicament. Adding cellulose also ensures the stability of this structure, so that adapalene nanoparticles can be stably dispersed. During the water loss process of the medicament, cellulose can assist in forming a slightly frosted texture protective film on the surface of the medicament, isolating the wiping of the medicament by external fingers, clothes, etc., and delaying the water loss process of the adapalene topical agent.

[0033] Preferably, the dosage of artemisia sphaerocephala gum accounts for 32% of the total mass of the gel substrate.

[0034] Preferably, the raw materials of the above adapalene topical agent by mass fraction include 7% of adapalene, 4% of gel substrate, 3% of cellulose, 1.5% of penetration enhancer, 22% of water-retaining agent, 2.5% of surfactant, and also include a pH regulator, and the rest is water.

[0035] In the raw materials of the adapalene topical agent provided by the present invention, the water-retaining agent is glycerol and liquid paraffin, and the mass ratio of the two is (1-3):1. For the convenience of comparison, in the following examples and comparative examples, the mass ratio of the two is 2:1.

[0036] Among the raw materials of the adapalene topical agent provided by the present invention, the surfactant is at least one of Tween 80, polyoxyethylene castor oil 60, polyoxyethylene hydrogenated castor oil 60, and polyethylene glycol stearate; the penetration enhancer is at least one of lauryl alcohol, menthol, geraniol, anethole, decyl methyl sulfoxide, and sodium tetradecyl sulfate. For the convenience of comparison, in the following examples and comparative examples, Tween 80 is uniformly selected as the surfactant, and a mixture of lauryl alcohol and menthol with a mass ratio of 1:1 is uniformly selected as the penetration enhancer.

[0037] The cellulose selected in the present invention can be obtained by the following method in addition to directly purchasing finished products that meet the requirements in the market:

[0038] (1) Wash, remove impurities, and dry wood, straw, and cotton and linen fibers until the moisture content ≤ 2%, and then mechanically crush them into fragments ≤ 3 mm;

[0039] (2) Add a mixture of sodium hydroxide and dimethyl sulfoxide with a volume ratio of 1:10, stir at room temperature for 1 h, and the mass ratio of the fiber to the mixture is 1:10;

[0040] (3) Filter and separate to obtain fibers, wash them, add water to prepare a suspension with a mass fraction of 5%, and grind with a colloid mill until the diameter ≤ 1 μm; then homogenize 3 times under a pressure of 1400 MPa;

[0041] (4) Centrifuge to remove the supernatant, dry the product until the water content ≤ 1%, and obtain nanofibers with a diameter of 5 - 10 nm and a length of 2.5 - 10 μm.

[0042] The following examples and comparative examples also provide a preparation method for an adapalene topical agent, and the steps include:

[0043] (1) Heat and stir the water-retaining agent until it becomes liquid (if it is already liquid, heating and stirring are not required), and mix adapalene, the penetration enhancer, and the water-retaining agent evenly to obtain a first mixture;

[0044] For the above step (1), only the raw materials need to be evenly mixed. Generally, the mixing conditions are stirring at 200 - 300 rpm for 5 - 10 min; for the convenience of comparison in the following examples, the mixing conditions are selected as stirring at 200 rpm for 10 min.

[0045] (2) Mix the gel substrate, cellulose, and 30 - 60% of the total water volume evenly to obtain a second mixture;

[0046] For the above step (2), only the raw materials need to be evenly mixed. Generally, stirring at 200 - 300 rpm for 5 - 10 min is sufficient; for the convenience of comparison in the following examples, the mixing conditions are selected as stirring at 300 rpm for 10 min.

[0047] (3) Mix the pH regulator, surfactant and the remaining water evenly to obtain a third mixture;

[0048] For the above step (2), it is only necessary to mix the raw materials evenly. Generally, stirring at 200 - 300 rpm for 5 - 10 min is sufficient; for the convenience of comparison in the following examples, the mixing condition is selected as stirring at 200 rpm for 5 min.

[0049] (4) Mix the first mixture and the second mixture, shear, and finally add them to the third mixture for dispersion to obtain an adapalene topical agent;

[0050] Generally, the conditions for shear emulsification in the above step (4) are shear at 10000 - 12000 rpm for 20 - 30 min; the conditions for dispersion are dispersion at 800 - 1000 rpm for 1 - 1.5 h.

[0051] For the convenience of comparison in the following examples, preferably, the conditions for shear emulsification can be selected as shear at 12000 rpm for 30 min and dispersion at 800 rpm for 1 h.

[0052] Next, an adapalene topical agent of the present application will be described in detail with reference to examples, comparative examples and experimental data.

[0053] Example 1

[0054] The adapalene topical agent provided in this example, its raw materials by mass fraction include 7% of adapalene, 4% of gel base material (the mass ratio of poloxamer 188 and artemisia sphaerocephala gum is 68:32), 3% of cellulose (prepared by the above mechanical grinding, with a diameter of 5 - 8 nm and a length of 5 - 10 μm), 1.5% of penetration enhancer (the mass ratio of lauryl alcohol and menthol is 1:1), 22% of water - retaining agent (the mass ratio of glycerol and liquid paraffin is 2:1), 2.5% of surfactant (Tween 80), and also includes a pH regulator, and the rest is water.

[0055] Example 2

[0056] The adapalene topical agent provided in this example, its raw materials by mass fraction include 7.5% of adapalene, 8% of gel base material (the mass ratio of poloxamer 188 and artemisia sphaerocephala gum is 68:32), 2% of cellulose (prepared by the above mechanical grinding, with a diameter of 5 - 8 nm and a length of 5 - 10 μm), 0.5% of penetration enhancer (the mass ratio of lauryl alcohol and menthol is 1:1), 25% of water - retaining agent (the mass ratio of glycerol and liquid paraffin is 2:1), 2% of surfactant (Tween 80), and also includes a pH regulator, and the rest is water.

[0057] Example 3

[0058] The adapalene topical agent provided in this embodiment comprises, by mass fraction, 4.5% of adapalene, 3.5% of a gel base material (with a mass ratio of poloxamer 188 to artemisia sphaerocephala gum of 68:32), 4.5% of cellulose (prepared by the above-mentioned mechanical grinding, with a diameter of 5 - 8 nm and a length of 5 - 10 μm), 2% of a penetration enhancer (with a mass ratio of lauryl alcohol to menthol of 1:1), 18% of a water retention agent (with a mass ratio of glycerol to liquid paraffin of 2:1), 5% of a surfactant (Tween 80), and also includes a pH value regulator, with the balance being water.

[0059] Example 4

[0060] The difference between the adapalene topical agent provided in this embodiment and that in Example 1 lies in that the mass ratio of poloxamer 188 to artemisia sphaerocephala gum selected for the gel base material is 75:25.

[0061] Example 5

[0062] The difference between the adapalene topical agent provided in this embodiment and that in Example 1 lies in that the mass ratio of poloxamer 188 to artemisia sphaerocephala gum selected for the gel base material is 65:35.

[0063] Comparative Example 1

[0064] The difference between the adapalene topical agent provided in this embodiment and that in Example 1 lies in that the mass ratio of poloxamer 188 to artemisia sphaerocephala gum selected for the gel base material is 80:20.

[0065] Comparative Example 2

[0066] The difference between the adapalene topical agent provided in this embodiment and that in Example 1 lies in that the mass ratio of poloxamer 188 to artemisia sphaerocephala gum selected for the gel base material is 60:40.

[0067] Comparative Example 3

[0068] The difference between the adapalene topical agent provided in this embodiment and that in Example 1 lies in that no cellulose or other substitute for cellulose is added.

[0069] Comparative Example 4

[0070] The difference between the adapalene topical agent provided in this embodiment and that in Example 1 lies in that artemisia sphaerocephala gum is not selected for the gel base material, and all poloxamer 188 is used instead.

[0071] Test Example

[0072] 1. Stability test and accelerated stability test

[0073] (1) Coating test: Take an appropriate amount of the finished adapalene topical agent of each example and comparative example, apply it on the arm with a coating thickness of not less than 2 mm; evaluate the ease of application, and check the state of the topical agent after 10 min, 1 h, 2 h, 4 h, and 6 h of application;

[0074] (2) Cold resistance test: Take 10 g of the finished adapalene topical agent of each example and comparative example, fill it into a 10 ml ampoule, seal it, and let it stand in an environment of -18 °C for 24 h, and observe the layering situation;

[0075] (3) Heat resistance test: Take 10 g of the finished adapalene topical agent of each example and comparative example, fill it into a 10 ml ampoule, seal it, and place it in an environment of 55 ± 2 °C for 10 days, and take samples on the 3rd, 5th, and 10th days after the start of the test to observe the layering situation;

[0076] (4) Accelerated stability test: To further investigate the stability of the adapalene topical agent of the present invention, according to the relevant regulations in the "Guidelines for Stability Testing of Bulk Drugs and Drug Products" in Appendix XIX C of the Chinese Pharmacopoeia 2010 Edition, take the adapalene topical agents prepared in each example and comparative example, and place them at a temperature of 30 ± 2 °C and a relative humidity of 65 ± 5% for 6 months. Samples are taken at 1, 2, 3, and 6 months respectively, and according to the quality standards, the properties and layering phenomena of each sample are detected, and the determination is repeated 3 times.

[0077] The test results of the stability test, accelerated stability test are shown in Table 1 below.

[0078] Table 1 Test results of stability and accelerated stability

[0079]

[0080] As can be seen from Table 1, for the adapalene topical agents prepared in the above Examples 1-5 and Comparative Examples 1-2, after being applied on the arm, they were initially in a viscous transparent or semi-transparent gel form, and an appropriate amount of the agent could adhere when touching the surface of the gel with a finger, indicating that the adhesion of the agent to the skin is good.

[0081] At 10 minutes after application of the adapalene topical agent of Example 1, a visible film layer appeared on the surface of each topical agent, and a certain thickness could be felt by touch. This is because the agent lost water and, with the synergistic cooperation of artemisia sphaerocephala gum and cellulose, a gel network structure gradually formed inside the agent layer, and a protective film formed on the surface of the agent layer. Under the action of cellulose, the strength of the protective film was ensured. The protective film can isolate the agent gel from the outside and prevent the drug from being wiped off by fingers or clothing. During the period from 1 hour to 5 hours after application, the protective film layer on the surface of the agent gradually thickened. The agent gel under the protective film layer changed from being deformed after finger pressure at the beginning to showing no obvious deformation after finger pressure. At this time, when the agent was peeled off, the agent gel on the side close to the skin was still relatively soft, and a small amount of gel could be scraped off with a fingernail. From 5 hours and 50 minutes to 6 hours after application, the entire topical agent had hardened, and there was no obvious deformation when the agent was gently pressed. The edge of the agent layer was slightly upturned, and it was very easy to directly pick off or peel off the whole thing with the hand. The changes in the agent gels of the other several examples were not much different from those of Example 1, except that the order of appearance of each stage time node was slightly different. The agent gel of Comparative Example 1 hardened relatively quickly. Although the gel state was good and it was easy to coat, the difficulty of finger coating was slightly greater than that of Examples 1-5; the agent gel of Comparative Example 2 hardened relatively slowly; the protective film formed by the agent gel of Comparative Example 3 had low strength and insufficient support, and the hardening speed was slow over time. During this period, it was easy for a finger to pierce the protective film and scrape off the gel agent under the film; for the topical agent prepared in Comparative Example 4, the gel state was good, but the stability was slightly poor, and it was prone to delamination during long-term storage, and the water loss speed of the gel was relatively fast, which would affect the transdermal absorption of the adapalene drug.

[0082] After analysis, it is preliminarily considered that the mass ratio of poloxamer 188 and artemisia sphaerocephala gum, as well as the selection of cellulose and artemisia sphaerocephala gum, have an impact on the state, hardening process and stability of the drug gel. This may be due to inappropriate proportion of raw material usage or the lack of cellulose or artemisia sphaerocephala gum, which affects the microscopic structure of the gel.

[0083] 2. In vitro release test

[0084] The adapalene topical agents prepared in Examples 1-5 and Comparative Examples 1-4 were subjected to in vitro release tests. The drug release test was carried out through a diffusion cell. A 5-μm artificial fiber membrane was used as the permeation material, a 25% ethanol solution was used as the receiving medium, the drug dosage in the supply chamber was 0.2 ml, the volume of the receiving cell was 7 mL, and the effective permeation area was 3.14 cm 2Place the diffusion cell in a thermostatic water bath (37°C ± 0.5°C), and place the magnetic stirrer under the thermostatic water bath with a stirring speed of 300 r / min. At 5 min, 30 min, 1 h, 1.5 h, 2 h, 2.5 h, 3 h, 3.5 h, 4 h, 4.5 h, 5 h, 5.5 h, 6 h, 6.5 h, and 7 h respectively, take out 5 mL of the receiving solution, and simultaneously supplement it with the same volume of blank receiving solution. Centrifuge the obtained samples, take the supernatant, analyze the receiving solution by liquid chromatography, and obtain the drug release rate by dividing the drug release amount by the drug release time.

[0085] The specific calculation method of the drug release rate is as follows: Assume the total amount of the drug is w, the drug release amount at 10 min is w0, and the cumulative drug release amount at 30 min is w1. Then the drug release rate at 10 min is (w0 / w) / (1 / 6), and the drug release rate at 30 min is (w1 - w0) / (1 / 3). It should be noted that 1 / 6 in (w0 / w) / 0.25 refers to 10 min, that is, (1 / 6) h, which is 0.25 h; 1 / 3 in (w1 - w0) / 0.25 is 30 min - 10 min = 20 min, that is, (1 / 3) h. Plot the drug release curves of the adapalene topical agents of Examples 1-4 and Comparative Examples 1-4 respectively, as shown in Figure 1 , 2 respectively.

[0086] From Figure 1 it can be seen that for the adapalene topical agents prepared in Examples 1-4, the change curves of the drug release rate after administration are basically the same; the drug release rate peaks approximately at 2 - 2.5 h, and then the drug release rate decreases steadily. By the 7th h of sampling, the drug release rate still reaches more than 2%.

[0087] From Figure 2 it can be seen that the drug release rates of Comparative Examples 1-4 vary. Among them, in Comparative Examples 1 and 2, due to the large change in the component ratio of the gel substrate, it has an obvious impact on the drug sustained-release rate, either too fast or too slow, ultimately resulting in the drug release rate peak appearing too early or too late. In Comparative Examples 3 and 4, due to the lack of cellulose or Artemisia sphaerocephala gum, it also has an adverse impact on the drug release rate, resulting in too fast drug release rate in the initial stage and too sharp decrease in the drug release rate in the later stage. These are not conducive to maintaining the drug concentration at the affected site. Only by using the raw material ratio of the gel substrate of the present invention and the synergistic cooperation of the gel substrate and cellulose can a relatively stable drug release concentration be maintained within a suitable time period.

[0088] In summary, the adapalene topical agent provided by the present invention has good adhesion performance, avoiding accidental erasure of the gel. By selecting cellulose and Artemisia sphaerocephala gum in the raw materials, it can provide a certain degree of strength support for the topical agent during the solidification process, and form a film layer on the surface of the topical agent that gradually thickens as the water evaporates, regulating the sustained release of the drug, ensuring the reasonable adaptation of the drug release rate and the water loss and hardening process after the adapalene topical agent is applied, and it is convenient to use by visually and tactilely confirming whether the agent can be peeled off with the naked eye and fingers.

[0089] The above specific embodiments have described the implementation of the present invention in detail. However, the present invention is not limited to the specific details in the above embodiments. Within the scope of the claims and technical concept of the present invention, various simple modifications and changes can be made to the technical solution of the present invention, and these simple variations all belong to the protection scope of the present invention.

Claims

1. An adapalene topical preparation, characterized in that, Its raw materials by mass fraction include 4.5 - 7.5% of adapalene, 3.5 - 8% of gel base material, 2 - 4.5% of cellulose, 0.5 - 2% of penetration enhancer, 18 - 25% of water-retaining agent, 2 - 5% of surfactant, and also include a pH regulator, with the balance being water; the dosage of the pH regulator is to adjust the pH of the adapalene topical agent to 7.5 - 8; The gel base material includes poloxamer or carbomer, and also includes artemisia sphaerocephala gum, and the dosage of the artemisia sphaerocephala gum accounts for 25 - 35% of the total mass of the gel base material; the diameter of the cellulose is 5 - 10 nm, and the length is 2.5 - 10 μm.

2. The adapalene topical agent according to claim 1, wherein The dosage of the artemisia sphaerocephala gum accounts for 32% of the total mass of the gel base material.

3. The adapalene topical agent according to claim 1, characterized in that, The water-retaining agent is glycerol and liquid paraffin, and the mass ratio of the two is (1 - 3):

1.

4. The adapalene topical agent according to claim 1, characterized in that, The surfactant is at least one of tween 80, polyoxyethylene castor oil 60, polyoxyethylene hydrogenated castor oil 60, and polyethylene glycol stearate; the penetration enhancer is at least one of lauryl alcohol, menthol, geraniol, anethole, decyl methyl sulfoxide, and sodium lauryl sulfate.

5. The adapalene topical agent according to any one of claims 1-4, characterized in that, Its raw materials by mass fraction include 7% of adapalene, 4% of gel base material, 3% of cellulose, 1.5% of penetration enhancer, 22% of water-retaining agent, 2.5% of surfactant, and also include a pH regulator, with the balance being water.

6. The preparation method of the adapalene topical agent according to any one of claims 1-4, characterized in that, It includes the following steps: Mix the adapalene, penetration enhancer, and water-retaining agent evenly to obtain a first mixture; Mix the gel base material, cellulose, and 30 - 60% of the total water volume evenly to obtain a second mixture; Mix the pH regulator, surfactant, and the remaining water evenly to obtain a third mixture; Mix the first mixture and the second mixture, shear, and finally add them to the third mixture for dispersion to obtain the adapalene topical agent.

7. The preparation method of the adapalene topical agent according to claim 6, characterized in that, The conditions for the shear are 10000 - 12000 rpm for 20 - 30 min; the conditions for the dispersion are 800 - 1000 rpm for 1 - 1.5 h.

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