Permeation-enhanced hair blackening emulsion containing melanin proliposome

Abstract

The invention relates to the technical field of daily chemicals, in particular to permeation-enhanced hair blackening emulsion containing melanin precursor liposome. The invention aims to solve the problems that the existing hair-blacking product damages the hair quality, the effect is not lasting or the hair-blacking product is difficult to permeate into the hair shaft, and the core of the hair-blacking product is that a melanin precursor is wrapped in a liposome formed by phospholipid and cholesterol to form a melanin precursor liposome dispersion liquid, and the melanin precursor liposome dispersion liquid is compounded with a permeation enhancer. According to the design, the biocompatibility and the targeting property of the lipidosome are utilized, reversible disturbance of the penetration enhancer on a hair small skin barrier is combined, the melanin precursor is synergistically promoted to efficiently penetrate into the hair skin, and natural and lasting hair blackening is achieved from the interior.

Description

TECHNICAL FIELD

[0001] The present application relates to the technical field of daily chemicals, more particularly, it relates to a permeation-enhanced hair blackening emulsion containing liposome of melanin precursor. BACKGROUND

[0002] The problem of white hair plagues people of all ages. The hair blackening products on the market at present mainly fall into two categories: chemical synthetic hair dyes and plant-derived hair blackening products.

[0003] Chemical synthetic hair dyes (such as products containing p-phenylenediamine) develop color through the oxidative coupling of small-molecule dyes after the dyes penetrate the cortex of the hair coat, and although they have fast coloring and a wide range of color choices, they generally have problems such as skin sensitization, damage to the hair quality, and potential carcinogenic risks.

[0004] Plant-derived hair blackening products (such as Henna flowers and extracts of Radix Polygoni Multiflori) are generally considered to be safer, but their mechanisms of action are mostly to form a coating on the surface of the hair or to perform surface dyeing, and they have unnatural color, are prone to falling off, have poor durability, and have a slow effect. More importantly, they are difficult to effectively deliver the real pigment ingredients to the inside of the hair shaft, and thus cannot achieve the natural hair blackening effect from the inside to the outside.

[0005] Melanin is the source of the natural color of the hair. Direct supplementation of melanin or its precursor substances is a theoretically most ideal approach to hair blackening. However, the melanin precursors (such as dopamine and tyrosine) have small molecular weights, unstable properties, are prone to oxidation and inactivation, and are difficult to penetrate the dense barrier of the hair cuticle to reach the target site of the hair cortex.

[0006] As a new type of carrier, liposomes have the advantages of good biocompatibility, biodegradability, and targeting, and have been widely used in drug delivery. When applied to hair blackening products, they are expected to protect the melanin precursors and promote the transdermal or transcutaneous absorption of active ingredients by virtue of their similar properties to biological membranes. However, how to effectively combine the liposome technology with the demand for hair blackening and solve the problems of stability and penetration efficiency in actual formulations is still a technical problem to be solved in the field. SUMMARY

[0007] The present application aims at overcoming the deficiencies of the prior art, and provides a permeation-enhanced hair blackening emulsion containing liposome of melanin precursor, which has natural, durable, safe and efficient hair blackening effect.

[0008] To achieve the above-mentioned purpose, the present application realizes the following technical scheme:

[0009] The permeation-enhanced hair blackening emulsion containing liposome of melanin precursor comprises the following components: a liposome of melanin precursor dispersion, a penetration enhancer, and a residual emulsion base; the liposome of melanin precursor dispersion is formed by wrapping the melanin precursor in the liposome and dispersing it in the buffer.

[0010] Preferably, the melanin precursor is selected from one or more of levodopa, tyrosine, dopamine, or pharmaceutically acceptable salts or derivatives thereof.

[0011] Preferably, the liposomes are composed of phospholipids and cholesterol, wherein the phospholipids are selected from one or more of soybean lecithin, hydrogenated soybean lecithin, phosphatidylcholine, and phosphatidylethanolamine.

[0012] Preferably, the buffer solution is a phosphate buffer solution with pH = 6.0.

[0013] Preferably, the penetration enhancer is selected from one or more of azone, oleic acid, linoleic acid, propylene glycol, menthol, and eucalyptol.

[0014] Preferably, based on the total weight of the penetration-enhancing hair darkening emulsion as 100%, the content of each component is as follows: melanin precursor liposome dispersion 1%-20%, penetration enhancer 0.5%-5%, and the remainder being the emulsion matrix.

[0015] Preferably, the emulsion matrix comprises an aqueous phase, an oil phase, and an emulsifier; the aqueous phase comprises deionized water, a humectant, and a thickener; and the oil phase comprises moisturizing oils, an emulsifier, and a preservative.

[0016] Preferably, the preparation method of the penetration-enhancing hair-darkening emulsion includes the following steps:

[0017] S1: Preparation of melanin precursor liposomes: Phospholipids and cholesterol are dissolved in an organic solvent to form a lipid phase; melanin precursors are dissolved in a buffer solution to form an aqueous phase; the aqueous phase is added to the lipid phase under stirring, and after emulsification and ultrasonic treatment, the organic solvent is removed to obtain a melanin precursor liposome dispersion.

[0018] S2: Preparation of emulsion matrix: Prepare aqueous phase and oil phase separately. After heating to 70-80℃, add oil phase to aqueous phase under high-speed shearing for emulsification. After homogenization, cool to room temperature.

[0019] S3: Mixing: At a temperature below 40°C, the melanin precursor liposome dispersion and the penetration enhancer obtained in step S1 are slowly added to the emulsion matrix obtained in step S2 and stirred evenly to obtain the hair darkening emulsion.

[0020] Melanin precursor liposomes are the active ingredient delivery system of this invention. They encapsulate melanin precursors (such as L-DOPA and tyrosine) within a lipid bilayer composed of phospholipids and cholesterol. This encapsulation structure not only protects the melanin precursors from premature oxidation during storage and use, but also utilizes its biocompatibility with biological membranes to efficiently carry and penetrate the hair cuticle through "cell membrane fusion," reaching the hair cortex and mimicking the natural color formation process within the hair shaft.

[0021] Permeation enhancers can further improve the permeation efficiency of liposomes. In this invention, a permeation enhancer composed of azone, oleic acid and other compounds is used in the formulation to reversibly disturb the lipid structure between the skin scales of hair cells, temporarily increase the intercellular space, open up a "green channel" for the permeation of liposomes, and play a synergistic role.

[0022] Emulsion bases provide products with the necessary form, spreadability, stability, and basic care functions. They consist of an aqueous phase, an oil phase, and emulsifiers, providing a stable and favorable environment for active ingredients.

[0023] The present invention has the following beneficial effects:

[0024] (1) Targeted and efficient: Using liposomes as carriers, melanin precursors are precisely delivered to the hair cortex, replenishing pigment from the inside of the hair root. The hair darkening effect is from the inside out, extremely natural, and the color is long-lasting.

[0025] (2) High safety: It avoids the use of toxic and harmful chemical oxidizing dyes such as p-phenylenediamine. The main components are biocompatible phospholipids and melanin precursors, which greatly reduces the risk of allergies and irritation.

[0026] (3) Good stability: Liposome encapsulation effectively protects the activity of melanin precursors and extends the shelf life of the product.

[0027] (4) Synergistic effect: The combination of liposome technology and penetration enhancer significantly improves the penetration efficiency of active ingredients into hair, solving the technical problem of difficult penetration of plant hair darkening products.

[0028] (5) Multi-effect care: The phospholipids, oils and other ingredients in the formula have a good nourishing and repairing effect on hair, and can achieve hair care effect while darkening hair. Detailed Implementation

[0029] The technical solution of the present invention will be further described below with reference to the embodiments. Obviously, the described embodiments are only a part of the embodiments of the present invention, and not all of them. All other embodiments obtained by those skilled in the art based on the embodiments of the present invention without creative effort are within the scope of protection of the present invention. Unless otherwise specified, the methods or operations used in the embodiments are conventional methods or operations in the art.

[0030] This application provides a general and / or specific description of the materials and experimental methods used in the experiments. In the following examples, unless otherwise specified, % represents wt%, i.e., weight percentage. Reagents or instruments used, unless otherwise specified, are all commercially available conventional reagent products.

[0031] Example 1

[0032] Preparation of melanin precursor liposome dispersion: Weigh 2.0 g of soybean lecithin and 0.5 g of cholesterol, dissolve them in 20 mL of anhydrous ethanol, place the solution in a round-bottom flask, and evaporate by rotary evaporation in a 40 °C water bath until a uniform lipid film forms on the flask wall. Separately weigh 1.0 g of levodopa, dissolve it in 100 mL of phosphate buffer solution (pH 6.0), and heat it to 50 °C in a water bath. Pour this levodopa solution into the flask containing the lipid film and hydrate it by vigorous shaking for 30 minutes. Subsequently, sonicate the resulting suspension using a probe (300 W power, 2 seconds operation, 3 seconds interval, total duration 5 minutes) to obtain a levodopa liposome dispersion with uniform particle size distribution.

[0033] Based on a total mass of 100% for the penetrating and enhancing hair darkening emulsion, its formulation consists of: 10.0% of the melanin precursor liposome dispersion prepared above, 1.5% azone, 1.5% oleic acid, 3.0% glycerin, 0.2% carbomer, 2.0% cetearyl alcohol, 5.0% jojoba oil, 1.2% Tween-80, 0.8% Span-80, 0.2% methylparaben, and deionized water to 100%.

[0034] Preparation of the emulsion matrix: According to the above formula, deionized water, glycerol, and carbomer are mixed and stirred until the carbomer is fully swollen to obtain the aqueous phase; cetearyl alcohol, jojoba oil, Tween-80, Span-80, and methylparaben are mixed and heated to 75°C to dissolve evenly to obtain the oil phase; the oil phase is slowly added to the aqueous phase under high-speed shear (8000 rpm), and shear emulsification is continued for 10 minutes, then homogenized for 5 minutes, and naturally cooled to below 35°C to obtain the emulsion matrix.

[0035] Preparation of penetrating and enhanced hair darkening emulsion: Under low-speed stirring, melanin precursor liposome dispersion, azone and oleic acid are added slowly in sequence to the emulsion matrix prepared above. After stirring evenly, the pH of the emulsion is adjusted to 5.5-6.0 with triethanolamine. After aging for 24 hours, it is filled to obtain the final product.

[0036] Example 2

[0037] Compared with Example 1, the difference is that 1.0 g of levodopa and 0.5 g of tyrosine were weighed and dissolved in 100 mL of phosphate buffer solution with pH = 6.0, and heated to 50°C in a water bath. The remaining components and preparation methods are the same as in Example 1.

[0038] Example 3

[0039] Compared to Example 1, the mass fraction of melanin precursor liposome dispersion in the penetrating and enhancing hair darkening emulsion increased from 10% to 15.0%. The remaining components and preparation method were the same as in Example 1.

[0040] Example 4

[0041] Compared to Example 1, the mass fraction of melanin precursor liposome dispersion in the penetrating and enhancing hair darkening emulsion increased from 10% to 20.0%. The remaining components and preparation method were the same as in Example 1.

[0042] Comparative Example 1

[0043] Compared to Example 1, a plain levodopa solution without liposomes was used instead of the melanin precursor liposome dispersion. Specifically, 0.5 g of levodopa was dissolved in 100 mL of phosphate buffer at pH 6.0 to prepare the plain levodopa solution. The remaining components and preparation methods were the same as in Example 1.

[0044] Comparative Example 2

[0045] Compared with Example 1, the permeation enhancer is omitted and an equal amount of deionized water is added, while the remaining components and preparation methods are the same as in Example 1.

[0046] To verify the technical effect of the hair darkening emulsion containing melanin precursor liposomes provided by the present invention, especially the synergistic effect of the melanin precursor liposome dispersion and the penetration enhancer, a series of comparative experiments were designed in this section to systematically evaluate the samples obtained in Examples 1-4 and Comparative Examples 1-2.

[0047] (1) Liposome encapsulation efficiency and storage stability determination: The determination was performed using ultracentrifugation-high performance liquid chromatography (HPLC). Each sample was diluted 10-fold and centrifuged at 40,000 rpm for 30 minutes in a low-temperature ultracentrifuge to precipitate the unencapsulated free melanin precursor. The supernatant was collected, along with an equal volume of a completely demulsified sample solution in methanol. The free drug concentration (Cfree) and total drug concentration (Ctotal) were determined using HPLC (chromatographic conditions: C18 column, mobile phase: methanol:phosphate buffer = 10:90, detection wavelength 280 nm). The encapsulation efficiency (EE%) was calculated using the following formula:

[0048] EE% = (total C - free C) / total C × 100%

[0049] Meanwhile, each sample was placed in a 40℃ constant temperature chamber for accelerated stability testing, and its encapsulation efficiency was measured on day 0, day 30 and day 60, respectively. The results are shown in Table 1.

[0050] Table 1: Results of liposome encapsulation efficiency and accelerated stability test

[0051]

[0052]

[0053] As shown in Table 2, the initial encapsulation efficiency of the melanin precursor liposomes prepared in each embodiment of the present invention was higher than 87%, demonstrating excellent encapsulation ability. After 60 days of accelerated testing, the encapsulation efficiency retention rate of the samples in each embodiment was higher than 82%, with a decrease of less than 5%, proving that the liposome encapsulation structure can effectively protect the melanin precursor, significantly delay its oxidative degradation, and ensure the stability of the active ingredient in the product during its shelf life. Comparative Example 1, which did not use liposome technology, had its active ingredient significantly degraded during the accelerated testing, making effective measurement impossible.

[0054] (2) In vitro hair permeability test: Human gray hair bundles of consistent origin and similar diameter were selected, pretreated, and fixed in a Franz diffusion cell with the cuticle facing the supply cell. Samples from Example 1, Comparative Example 1, and Comparative Example 2 were used as the supply solution, and the receiving cell contained phosphate buffer solution at pH 7.4. The system temperature was maintained at 37°C with continuous magnetic stirring. At predetermined time points (2, 4, 8, 12, 24 hours), 0.5 mL samples were taken from the receiving cell, and isothermal and equal volumes of fresh phosphate buffer solution were added immediately. The samples were analyzed by HPLC, and the cumulative permeation of levodopa (μg / cm³) was calculated. 2 ), and plot the cumulative permeate-time curve. The slope of the steady-state portion of the curve is the permeation rate (μg / cm). 2 / h), the results are shown in Table 2.

[0055] Table 2: Results of in vitro hair permeability test

[0056]

[0057]

[0058] As shown in Table 2, the penetration rate and cumulative permeation over 24 hours of Example 1 were significantly higher than those of Comparative Example 1 and Comparative Example 2. Specifically, the penetration efficiency of Example 1 was approximately 4.7 times that of Comparative Example 1 (unencapsulated) and approximately 1.7 times that of Comparative Example 2 (without penetration enhancer). This result strongly demonstrates that the present invention, through the synergistic effect of liposome encapsulation and penetration enhancer, can greatly promote the penetration of melanin precursors into the hair cuticle barrier, thus solving the technical problem of weak hair penetration of active ingredients.

[0059] (3) Evaluation of hair darkening effect: Gray hair bundles were randomly divided into six groups, corresponding to Examples 1-4 and Comparative Examples 1-2, respectively. Each group of gray hair bundles was immersed in the corresponding sample 3 times a week for 30 minutes each time, simulating daily use. The treatment period was 8 weeks. The L value, a value, and b value of the gray hair bundles were measured using a colorimeter at weeks 0, 2, 4, 6, and 8, and the total color difference ΔE (ΔE = √(ΔL)) was calculated. 2 +(Δa) 2 +(Δb) 2 The larger the ΔE value, the more obvious the color change. At the same time, 10 uninformed evaluators visually rated the uniformity and naturalness of the hair darkening effect (1-10 points, 10 points being the best), and the results are shown in Table 3.

[0060] Table 3: Hair darkening effect after 8 weeks of treatment

[0061] Group ΔE value Visual score Remark Example 1 18.6 8.7 Uniform color, natural gray-black, firm adhesion Example 2 17.9 8.5 Same effect as Example 1, natural and uniform Example 3 20.1 9.0 Deeper black hair effect, still natural Example 4 21.5 9.2 Deepest black hair effect, high naturalness Comparative Example 1 5.2 3.2 Light and uneven color, easy to fall off after washing Comparative Example 2 11.3 6.1 Color has a certain deepening, but uniformity is poor

[0062] Table 3 shows that the ΔE values ​​and visual scores of Examples 1-4 of this invention are significantly better than those of Comparative Examples 1-2. Examples 1 and 2 achieved natural, uniform, and long-lasting hair-darkening effects, proving the effectiveness of their core solution. Examples 3 and 4 further enhanced the hair-darkening effect by increasing the content of melanin precursor liposome dispersion, illustrating the dose-response relationship. Comparative Example 1 showed a weak effect, confirming that the active ingredients cannot function effectively without liposome protection; Comparative Example 2 had an intermediate effect but poor uniformity, indicating that the lack of a penetration enhancer leads to uneven ingredient penetration, affecting the naturalness of the final effect.

[0063] The above description is merely a preferred embodiment of the present invention. The scope of protection of the present invention is not limited to the above embodiments. All technical solutions falling within the scope of the present invention's concept are within the scope of protection of the present invention. It should be noted that for those skilled in the art, any improvements and modifications made without departing from the original intent of the present invention should also be considered within the scope of protection of the present invention.

Claims

1. A permeation-enhanced hair restorer containing liposome of a melanin precursor, characterized by, The hair blackening emulsion comprises the following components: a melanin precursor liposome dispersion, a penetration enhancer, and a balance of an emulsion base; the melanin precursor liposome dispersion is formed by a melanin precursor being wrapped in a liposome and dispersed in a buffer solution.

2. The penetration-enhanced hair restorer emulsion according to claim 1, wherein, The melanin precursor is selected from one or more of levodopa, tyrosine, dopamine, or a pharmaceutically acceptable salt or derivative thereof.

3. The penetration-enhanced hair restorer emulsion of claim 1, wherein, The liposome is composed of a phospholipid and cholesterol, wherein the phospholipid is selected from one or more of soybean lecithin, hydrogenated soybean lecithin, phosphatidylcholine, and phosphatidylethanolamine.

4. The penetration-enhanced hair restorer emulsion of claim 1, wherein, The buffer solution is a phosphate buffer solution with a pH of 6.

0.

5. The penetration-enhanced hair restorer emulsion of claim 1, wherein, The penetration enhancer is selected from one or more of azone, oleic acid, linoleic acid, propylene glycol, menthol, and eucalyptol.

6. The penetration-enhanced hair restorer emulsion of claim 1, wherein, The content of each component is 1-20% of the melanin precursor liposome dispersion, 0.5-5% of the penetration enhancer, and a balance of the emulsion base, based on the total weight of the penetration-enhanced hair blackening emulsion being 100%.

7. The penetration-enhanced hair restorer emulsion according to any one of claims 1 to 6, wherein, The emulsion base comprises an aqueous phase, an oil phase, and an emulsifier; the aqueous phase comprises deionized water, a humectant, and a thickening agent; the oil phase comprises an emollient oil, an emulsifier, and a preservative.

8. The penetration-enhanced hair restorer emulsion according to any one of claims 1 to 6, wherein, The preparation method comprises the following steps: S1: preparing a melanin precursor liposome: dissolving a phospholipid and cholesterol in an organic solvent to form a lipid phase; dissolving a melanin precursor in a buffer solution to form an aqueous phase; adding the aqueous phase to the lipid phase under stirring, and then performing emulsification and ultrasonic treatment, and removing the organic solvent to obtain a melanin precursor liposome dispersion; S2: preparing an emulsion base: preparing an aqueous phase and an oil phase, respectively, heating to 70-80°C, then adding the oil phase to the aqueous phase under high-speed shearing for emulsification, homogenizing, and then cooling to room temperature; S3: mixing: slowly adding the melanin precursor liposome dispersion prepared in step S1 and the penetration enhancer to the emulsion base prepared in step S2 under less than 40°C, and stirring uniformly to obtain the hair blackening emulsion.

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