Etoxosome hydrogel preparation containing plant sexual functional factors as well as preparation method and application of ethosome hydrogel preparation

Abstract

The invention relates to the technical field of medicines and cosmetics, in particular to an ethosome hydrogel preparation containing plant functional factors as well as a preparation method and application thereof. The ethosome hydrogel preparation is prepared from the following components in percentage by weight: 1.4 to 4 percent of plant composition, 20 to 40 percent of low-molecular-weight alcohol, 1.0 to 6.0 percent of soybean lecithin and the balance of deionized water, the plant composition is prepared from menthol, glycyrrhetinic acid, a cacumen biotae extract, a borneol extract, tanshinone and sophocarpidine. The ethosome hydrogel disclosed by the invention has a treatment effect on androgenetic alopecia, the problems of poor stability and low solubility in water of fat-soluble molecules such as plant extracts and the like are solved, and the prepared ethosome has a good particle size and can improve the skin permeability and bioavailability of medicines. The entrapment rate of the ethosome to the medicine is greater than 90%, which indicates that the ethosome can efficiently carry the medicine, reduce the waste of the medicine and improve the economical efficiency and effectiveness of treatment.

Description

Technical Field

[0001] The invention relates to the technical field of medicine and cosmetics, and in particular to an ethosome hydrogel preparation containing plant functional factors, a preparation method and application thereof. Background Art

[0002] Androgenetic alopecia (AGA) is the most common non-scarring alopecia in clinical practice. It can affect both men and women, but most of them are male patients. The typical symptoms of male patients are receding hairline and sparse and thinning hair on the top of the head. This disease not only affects the patient's appearance, but also has a negative impact on the patient's mental health and quality of life. The main causes of AGA include genetic factors and hormonal influences, among which dihydrotestosterone (DHT) is the main male hormone associated with this disease. DHT is a testosterone derivative formed by 5-α reductase, which binds to the androgen receptor (AR) of hair follicles, causing hair loss and inhibiting hair regeneration. The main methods for treating AGA currently include oral finasteride and topical minoxidil, but these drugs may cause scalp irritation such as itching and erythema, as well as application limitations such as male sexual dysfunction and female infertility. Therefore, it is urgent to find a natural medicine with high safety and the ability to significantly improve clinical symptoms as a new way to treat AGA.

[0003] Recent studies have found that some plant functional factors have the potential to inhibit androgenic alopecia. However, due to the poor water solubility of many plant extracts, their bioavailability is low, which makes it difficult to effectively absorb through the skin, thus limiting their application. Therefore, in order to more effectively utilize plant functional factors as therapeutic drugs, it is urgent to develop new targeted delivery strategies.

[0004] Among topical therapeutic drugs, transdermal administration is a crucial route that can avoid the first-pass metabolism problem of oral administration. Improving the bioavailability of transdermal drugs has always been an important challenge in the pharmaceutical field. The stratum corneum (SC) is the main barrier that leads to low penetration efficiency of topical transdermal drug delivery. In order to overcome these obstacles, a variety of technologies have been developed to enhance transdermal penetration and bioavailability, such as electroporation, nanocarriers and microneedles. Liposomes have been widely studied due to their similar structure and affinity with the stratum corneum of the skin. In particular, ethosomes, as an effective dermal and transdermal drug delivery system, have a high proportion of ethanol components that can change the lipid arrangement of the stratum corneum, enhance lipid fluidity and expand the size of the intercellular space, thereby significantly improving the transdermal rate and retention time of drugs in the skin, and facilitating the targeted delivery of drugs to the deep layers of the skin. However, ethosomes have strong fluidity and are difficult to fix on the skin surface for a long time, so a carrier is needed to ensure that the product stays on the skin surface. Carbomer is a non-irritating cross-linked acrylic polymer with thickening properties. It is currently widely used in the preparation of hydrogels in the cosmetics and pharmaceutical industries. This hydrogel not only provides better bioadhesion, but also enhances stability, creating favorable conditions for transdermal administration. Summary of the invention

[0005] The technical problem to be solved by the present invention is to provide an ethosome hydrogel preparation containing plant functional factors, a preparation method and an application thereof.

[0006] In order to solve the above technical problems, this application provides the following technical solutions:

[0007] A plant functional factor-containing ethosome hydrogel preparation comprises the following components in weight percentage: 1.4-4% of a plant composition, 20-40% of a low molecular weight alcohol, 1.0-6.0% of soybean lecithin, and the remainder being deionized water; wherein the plant composition consists of menthol, glycyrrhetinic acid, Platycladus orientalis leaf extract, borneol extract, tanshinone, and matrine.

[0008] Among them, the mass fractions of the components in the plant composition in the ethosome hydrogel preparation are: menthol 0.5%-1%, glycyrrhetinic acid 0.1%-0.5%, Platycladus orientalis leaf extract 0.1%-0.5%, borneol extract 0.5%-1%, tanshinone 0.1%-0.5%, and matrine 0.1%-0.5%.

[0009] Wherein, the low molecular weight alcohol is ethanol or propylene glycol.

[0010] Wherein, the average particle size of the alcohol body is 110nm-150nm.

[0011] Wherein, the particle size distribution of the alcohol body is 0.202PDI-0.371PDI.

[0012] The method for preparing the ethosome hydrogel preparation of the present invention comprises the following steps:

[0013] (1) dissolving soybean lecithin in a low molecular weight alcohol;

[0014] (2) adding menthol, glycyrrhetinic acid, Platycladus orientalis leaf, borneol extract, tanshinone, and matrine to a low molecular weight alcohol containing soybean lecithin as an alcohol phase;

[0015] (3) adding the aqueous phase to the alcohol phase and forming an alcohol body under a high-speed shearing machine;

[0016] (4) Carbomer U21 is added to the ethosome solution, stirred evenly, and neutralized with a triethanolamine solution to obtain an ethosome hydrogel.

[0017] Wherein, the low molecular weight alcohol is preferably ethanol, and the mass percentage of the low molecular weight alcohol is preferably 30%.

[0018] Wherein, the mass percentage of the soybean lecithin is preferably 4%.

[0019] The step (4) is specifically as follows: adding carbomer U21 powder to the alcohol body solution, fully swelling for 1 hour, stirring for 2-4 hours, and adjusting the pH with triethanolamine solution to obtain the alcohol body hydrogel, wherein the mass fraction of carbomer U21 is 3-5%, and the preferred mass content of carbomer U21 is 5%.

[0020] Among them, triethanolamine solution is added to adjust the pH value to 5.5-6.5, which is close to the pH value of the skin surface and can reduce the irritation of the external gel preparation to the skin.

[0021] The ethosome hydrogel preparation containing plant sexual function factors of the present invention can be used for preparing medicines or cosmetics for treating androgenic alopecia.

[0022] Compared with the prior art, the ethosome hydrogel preparation containing plant functional factors, the preparation method and the application of the present invention have at least the following beneficial effects:

[0023] (1) The ethosome hydrogel preparation containing plant functional factors of the present invention has a therapeutic effect on androgenic alopecia (AGA), providing a new, safe and effective treatment method for the treatment of AGA.

[0024] (2) The ethosome hydrogel of the present invention solves the problem of poor stability and low solubility in water of fat-soluble molecules such as plant extracts. The prepared ethosome has a good particle size and can improve the skin permeability and bioavailability of the drug. At the same time, the encapsulation efficiency (EE) of the ethosome for the drug is greater than 90%, indicating that the ethosome can efficiently carry the drug, reduce the waste of the drug, and improve the economy and effectiveness of the treatment.

[0025] (3) The ethosome hydrogel of the present invention exhibits a good drug sustained release effect, which means that the drug can be continuously released over a long period of time, thereby reducing the trouble of frequent drug application and potentially improving treatment compliance and efficacy.

[0026] (4) The ethosome hydrogel of the present invention exhibits good skin retention properties, which enables the drug to stay in the target area for a longer time, thereby improving the effect of local treatment.

[0027] (5) The preparation process of the present invention is simple, the reaction is easy to control, the stability is good, and it can be industrialized, and has broad promotion prospects in the field of hair growth.

[0028] The ethosome hydrogel preparation containing plant functional factors of the present invention, its preparation method and application are further described below in conjunction with the accompanying drawings. BRIEF DESCRIPTION OF THE DRAWINGS

[0029] Figure 1 1 is a scanning electron micrograph of the ethosome hydrogel preparation of the present invention.

[0030] Figure 2 This is the hair growth of mice.

[0031] Figure 3 HE staining results. DETAILED DESCRIPTION

[0032] In order to make the purpose, technical solution and advantages of the present invention more clearly understood, the present invention is further described in detail below in conjunction with the embodiments. It should be understood that the specific implementation cases described herein are only used to explain the present invention and are not used to limit the invention.

[0033] Example 1

[0034] An ethosome hydrogel containing plant functional factors, wherein the ethosome contains the following components by weight percentage: 1.4 plant composition, 30% ethanol, 4.0% soybean lecithin, and the rest is deionized water. The plant composition is 0.5% menthol, 0.1% glycyrrhetinic acid, 0.1% orientalis leaf extract, 0.5% borneol, 0.1% tanshinone, and 0.1% matrine. The mass content of carbomer U21 in the ethosome gel matrix is ​​5%. The menthol, glycyrrhetinic acid, orientalis leaf extract, borneol, matrine, and tanshinone used are all purchased from Shanghai MacLean Biochemical Technology Co., Ltd.

[0035] The preparation method is specifically as follows:

[0036] (1) dissolving soybean lecithin in a low molecular weight alcohol;

[0037] (2) Adding menthol, glycyrrhetinic acid, Platycladus orientalis leaf, borneol extract, tanshinone, and matrine to a low molecular weight alcohol containing soybean lecithin as an alcohol phase

[0038] (3) adding the aqueous phase to the alcohol phase and forming an alcohol body under a high-speed shearing machine;

[0039] (4) Carbomer U21 was added to the ethosome solution, and the mixture was fully swelled for 1 hour, and then stirred for 2-4 hours. The pH value was then adjusted to 5.5-6.5 with triethanolamine solution to obtain an ethosome gel.

[0040] Example 2

[0041] An ethosome hydrogel containing plant functional factors, wherein the ethosome contains the following components by weight percentage: 1.8% plant composition, 30% ethanol, 4.0% soybean lecithin, and the rest is deionized water; the mass content of carbomer U21 in the ethosome gel matrix is ​​5%. The plant composition is 0.5% menthol, 0.2% glycyrrhetinic acid, 0.2% orientalis leaf extract, 0.5% borneol, 0.2% tanshinone, and 0.2% matrine. The preparation method is the same as above.

[0042] Example 3

[0043] An ethosome hydrogel containing plant functional factors, wherein the ethosome contains the following components by weight percentage: 2.2% plant composition, 30% ethanol, 4.0% soybean lecithin, and the rest is deionized water; the mass content of carbomer U21 in the ethosome gel matrix is ​​5%. The plant composition is 0.5% menthol, 0.3% glycyrrhetinic acid, 0.3% orientalis leaf extract, 0.5% borneol, 0.3% tanshinone, and 0.3% matrine. The preparation method is the same as above.

[0044] Example 4

[0045] An ethosome hydrogel containing plant functional factors, wherein the ethosome contains the following components by weight percentage: 2.4% plant composition, 30% ethanol, 4.0% soybean lecithin, and the rest is deionized water; the mass content of carbomer U21 in the ethosome gel matrix is ​​5%. The plant composition is 0.5% menthol, 0.5% glycyrrhetinic acid, 0.5% orientalis leaf extract, 0.5% borneol, 0.2% tanshinone, and 0.2% matrine. The preparation method is the same as above.

[0046] Example 5

[0047] An ethosome hydrogel containing plant functional factors, wherein the ethosome contains the following components by weight percentage: 2.9% plant composition, 30% ethanol, 4.0% soybean lecithin, and the rest is deionized water; the mass content of carbomer U21 in the ethosome gel matrix is ​​5%. The plant composition is 0.75% menthol, 0.5% glycyrrhetinic acid, 0.2% orientalis leaf extract, 0.75% borneol, 0.5% tanshinone, and 0.2% matrine. The preparation method is the same as above.

[0048] Example 6

[0049] An ethosome hydrogel containing plant functional factors, wherein the ethosome contains the following components by weight percentage: 4% plant composition, 30% ethanol, 4.0% soybean lecithin, and the rest is deionized water; the mass content of carbomer U21 in the ethosome gel matrix is ​​5%. The plant composition is 1% menthol, 0.5% glycyrrhetinic acid, 0.5% orientalis leaf extract, 1% borneol, 0.5% tanshinone, and 0.5% matrine. The preparation method is the same as above.

[0050] Performance Test:

[0051] 1. Particle size and polydispersity index (PDI) of the ethosomes were determined by dynamic light scattering (Zetasizer Nano ZS; Malvern Ltd.; Malvern, UK). All measurements were performed at 25°C and repeated three times. Data are expressed as mean ± SD.

[0052] 2. The morphology of ethosomes was observed by scanning electron microscopy (SEM) (FE-SEM-SU8600; Hitachi Scientific Instruments (Beijing) Co., Ltd., Beijing, China).

[0053] 3. Animal experiment (by constructing an AGA mouse model and applying the ethosome gel to verify hair growth)

[0054] According to previous studies, the androgenic alopecia (AGA) model was established by intraperitoneal injection of 0.2 mL of dihydrotestosterone solution (DHT, 5 mg / mL) once a day for 20 days. In brief, mice were randomly divided into five groups (n=5), wherein the blank control group and the model group received topical application of normal saline, while the other groups received topical application of ethosome hydrogel of Example 6, tanshinone IIA aqueous solution, and 2% minoxidil tincture, respectively. Subsequently, photos of each group of mice were taken on the 1st, 6th, 12th, 15th, and 20th days to observe the hair growth of the mice (see Figure 2 After 20 days of treatment, the mice were anesthetized and killed, and the skin of the treated area was taken and fixed with 4% paraformaldehyde, then embedded in paraffin and sectioned. HE staining was performed to observe the growth of hair follicles, and the dermal thickness and hair follicle number of mice in each group were compared.

[0055] Experimental results:

[0056] 1. Particle size

[0057] As shown in Table 1, the particle size of the ethosome prepared in Example 6 is 137.23±0.32 nm, and the PDI is 0.298±0.21, indicating that the ethosome has a good particle size distribution.

[0058] Table 1 Particle size and PDI of the ethosomes of Example 6

[0059]

[0060] 2. SEM

[0061] The morphology of the alcohol body of Example 6 was observed by SEM. Figure 1 As shown, most of the alcohol bodies are spherical and evenly distributed, with a particle size of about 140nm.

[0062] 3. Animal Experiments

[0063] The hair growth of mice in the blank group was better than that in the model group and the ethosome hydrogel group, indicating that DHT can prolong the resting period of mouse hair. The skin of mice in the model group changed from pink to AGA model. The ethosome treatment found that compared with the model group, the skin color of mice in the ethosome hydrogel group turned black earlier, the hair grew faster, and the hair coverage rate was greater than that of the model group at the end of the experiment, indicating that ethosome gel can improve the prolonged resting period caused by AGA, promote the hair follicles of the AGA mouse model to enter the growth phase earlier, shorten the resting period, and promote hair growth (see Figure 2 ).

[0064] After 20 days of external application of the ethosome gel to AGA model mice, skin pathology showed that intraperitoneal injection of dihydrotestosterone solution into mice would affect the growth of hair follicles, reduce dermal thickness, reduce the number of hair follicles, and some hair follicles showed miniaturization, which is similar to the pathological characteristics of androgenic alopecia in clinical patients. After treatment with the ethosome gel, the dermal thickness and the number of hair follicles of mice increased, and there was a statistically significant difference compared with the model group, indicating that the ethosome gel can improve the changes in hair follicle growth and development induced by DHT and promote hair growth. Figure 3 .

[0065] HE staining showed that the dermal thickness and hair follicle number of mice in different groups were different. Figure 3 (B) showed that the dermal thickness of mice in the ethosome group and the blank group was higher than that in the model group, and there was a statistical difference between the two groups. There was no statistical difference in hair follicle count between the ethosome gel group and the blank group, and the number of hair follicles was greater than that in the model group and there was a statistical difference.

[0066] The embodiments described above are merely descriptions of preferred implementation modes of the present invention and are not intended to limit the scope of the present invention. Without departing from the design spirit of the present invention, various modifications and improvements made to the technical solutions of the present invention by ordinary technicians in this field should all fall within the protection scope determined by the claims of the present invention.

Claims

1. An ethosome hydrogel preparation containing plant functional factors, characterized in that: The invention comprises the following components in weight percentage: 1.4-4% of plant composition, 20-40% of low molecular weight alcohol, 1.0-6.0% of soybean lecithin, and the rest of deionized water; wherein the plant composition is composed of menthol, glycyrrhetinic acid, Platycladus orientalis leaf extract, borneol extract, tanshinone, and matrine.

2. The ethosome hydrogel preparation containing plant sexual function factors according to claim 1, characterized in that: The mass fractions of the components in the plant composition in the ethosome hydrogel preparation are: 0.5%-1% menthol, 0.1%-0.5% glycyrrhetinic acid, 0.1%-0.5% orientalis leaf extract, 0.5%-1% borneol extract, 0.1%-0.5% tanshinone and 0.1%-0.5% matrine.

3. The ethosome hydrogel preparation containing plant sexual function factors according to claim 1, characterized in that: The low molecular weight alcohol is ethanol or propylene glycol.

4. The ethosome hydrogel preparation containing plant sexual function factors according to claim 1, characterized in that: The average particle size of the alcohol body is 110nm-150nm.

5. The ethosome hydrogel preparation containing plant sexual function factors according to claim 1, characterized in that: The particle size distribution of the alcohol body is 0.202PDI-0.371PDI.

6. The method for preparing the ethosome hydrogel preparation according to any one of claims 1 to 5, characterized in that: The following steps are involved: (1) dissolving soybean lecithin in a low molecular weight alcohol; (2) adding menthol, glycyrrhetinic acid, Platycladus orientalis leaf, borneol extract, tanshinone, and matrine to a low molecular weight alcohol containing soybean lecithin as an alcohol phase; (3) adding the aqueous phase to the alcohol phase and forming an alcohol body under a high-speed shearing machine; (4) Carbomer U21 is added to the ethosome solution, stirred evenly, and neutralized with a triethanolamine solution to obtain an ethosome hydrogel.

7. The method for preparing the ethosome hydrogel preparation according to claim 6, characterized in that: The low molecular weight alcohol is ethanol, and the mass percentage of the low molecular weight alcohol is 30%.

8. The method for preparing the ethosome hydrogel preparation according to claim 6, characterized in that: The mass percentage of the soybean lecithin is 4%.

9. The method for preparing the ethosome hydrogel preparation according to claim 6, characterized in that: The step (4) specifically comprises adding carbomer U21 powder to the ethosome solution, fully swelling for 1 hour, stirring for 2-4 hours, and adjusting the pH to 5.5-6.5 with triethanolamine solution to obtain the ethosome hydrogel, wherein the mass fraction of carbomer U21 is 3-5%.

10. Use of the ethosome hydrogel preparation according to any one of claims 1 to 5 in the preparation of a medicine or cosmetic for treating androgenic alopecia.

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