A foam type cationic nanoemulsion hair toner and a preparation method thereof
By preparing a foam-type cationic nanoemulsion hair growth liquid modified with chitosan derivatives, the problems of insufficient permeability and retention of existing hair loss drugs have been solved, achieving better hair growth effect and skin compatibility.
Patent Information
- Authority / Receiving Office
- CN · China
- Patent Type
- Patents(China)
- Current Assignee / Owner
- SUZHOU UNIV
- Filing Date
- 2023-08-25
- Publication Date
- 2026-05-19
AI Technical Summary
Existing hair loss treatments such as minoxidil tincture and finasteride have skin irritation problems or insufficient penetration, are inconvenient to use, and cannot effectively promote hair growth.
A foam-type cationic nanoemulsion delivery carrier modified with chitosan derivatives was used to prepare a hair growth solution by mixing the drug with the chitosan derivative. The positive charge of chitosan was used to improve the interaction between the drug and the skin, and to enhance the drug's permeability and retention.
It increases the amount of drug retained and its penetration ability in the skin, prolongs the drug's retention time in the body, enhances the local treatment effect, reduces skin irritation, and promotes hair growth.
Smart Images
Figure CN117137867B_ABST
Abstract
Description
Technical Field
[0001] This invention belongs to the field of hair growth liquid technology, and particularly relates to a foam-type cationic nanoemulsion hair growth liquid and its preparation method. Background Technology
[0002] With rapid economic development, the fast pace of life, and increased work pressure, the incidence of hair loss is gradually rising and affecting younger people, attracting increasing attention from patients and doctors. Currently, the main medications for treating hair loss are minoxidil and finasteride. Minoxidil is mostly available as a topical tincture or gel, working by dilating blood vessels to treat hair loss. However, minoxidil tinctures are highly fluid and contain a large amount of organic solvents, easily causing skin problems such as itching, redness, and peeling. Minoxidil gels, due to their dosage form, have significantly lower drug penetration than other formulations, resulting in limited therapeutic effects. Finasteride is mostly available as an oral solid dosage form, requiring continuous use for more than one year to be effective. Furthermore, its use in pregnant women can cause malformations of the external genitalia in male fetuses and sexual side effects.
[0003] Nanoemulsions are transparent or semi-transparent systems with low viscosity, isotropic properties, and thermodynamic and kinetic stability, formed by combining an aqueous phase, an oil phase, surfactants, and co-surfactants in appropriate proportions. These systems typically have particle sizes of 10nm-100nm. Due to their fluid properties, small droplet size, strong permeability, and significant interaction with skin cells, nanoemulsions have been widely used in transdermal drug delivery. The surface charge of nanodroplets plays a crucial role in skin delivery. Positively charged nanoemulsions improve skin absorption and enhance interaction with epidermal cells. Positively charged nanoemulsions are superior to negatively charged nanoemulsions in local drug delivery. Nanoemulsion foam is a dosage form in which nanoemulsions are delivered through a specific drug delivery device, introducing air to generate a large amount of foam. The formation of the foam film reduces chemical and physical irritation at the drug delivery site, resulting in better practicality and compliance.
[0004] Chitosan, containing primary amino groups and carrying a positive charge, improves drug contact with the skin and cell membranes, effectively increasing drug retention in the skin. Simultaneously, chitosan possesses excellent adhesive properties, enhancing skin permeability and adhesion, and increasing the duration of drug penetration. Chitosan can expand drug penetration across various biological barriers, including the oral cavity, mucous membranes, transdermis, and eye. Its adhesive and highly permeable properties make it one of the most ideal transdermal drug delivery carriers, currently widely used in pharmaceuticals, cosmetics, and environmental protection. However, the limited water solubility of chitosan hinders its further application. Summary of the Invention
[0005] To address the aforementioned technical problems, this invention provides a foam-type cationic nanoemulsion hair growth liquid and its preparation method.
[0006] The first objective of this invention is to provide a method for preparing a foam-type cationic nanoemulsion hair growth solution, comprising the following steps:
[0007] S1. Mix the surfactant, oil phase material, co-surfactant and antibacterial agent evenly, add the drug, heat to dissolve it completely, and obtain the oil phase.
[0008] S2. The oil phase described in S1 is added dropwise to the aqueous phase, and fragrance is added to obtain the foam-type cationic nanoemulsion hair growth liquid; the aqueous phase includes chitosan derivatives and water.
[0009] In one embodiment of the present invention, in S1, the surfactant is polyethylene glycol glycerol caprylate and polyglycerol-3 oleate; the oil phase contains polyethylene glycol glycerol caprylate at a mass ratio of 5%-70% and polyglycerol-3 oleate at a mass ratio of 0.5%-20%.
[0010] In one embodiment of the present invention, in S1, the oil phase material is a medium-chain triglyceride, and the mass percentage of the medium-chain triglyceride in the oil phase is 0.1%-10%.
[0011] In one embodiment of the present invention, in S1, the co-surfactant is propylene glycol, and the mass percentage of propylene glycol in the oil phase is 1%-50%.
[0012] In one embodiment of the present invention, in S1, the antibacterial agent is phenoxyethanol and methylparaben; the mass percentage of phenoxyethanol in the oil phase is 0.01%-5%, and the mass percentage of methylparaben is 0.01%-5%.
[0013] In one embodiment of the present invention, in S1, the drug is finasteride and / or minoxidil, and the mass percentage of the drug in the oil phase is 0.1%-5%.
[0014] Further, in S1, the drug is finasteride, and the mass percentage of the drug in the oil phase is 0.1%-1%.
[0015] Furthermore, in S1, the drug is minoxidil, and the mass percentage of the drug in the oil phase is 1%-5%.
[0016] In one embodiment of the present invention, in S1, the heating temperature is 40°C-70°C.
[0017] In one embodiment of the present invention, in S2, the chitosan derivative is quaternized chitosan and / or carboxylated chitosan; the mass percentage of the chitosan derivative in the aqueous phase is 0.01%-5%; and the mass ratio of the oil phase to the aqueous phase is 1-2:3-4. By introducing functional groups through a series of chemical modifications such as carboxylation and quaternization of chitosan to form chitosan derivatives, its water solubility can be further improved.
[0018] Furthermore, the quaternized chitosan is selected from one or more of hydroxypropyltrimethylammonium chloride chitosan (HACC), N,N,N-trimethyl chitosan, N,N,N-trimethyl O-(2-hydroxy-3-trimethylammoniumpropyl) chitosan, and N-2-hydroxypropyldimethylethylammonium chloride chitosan. Quaternized chitosan is a type of water-soluble chitosan derivative obtained by introducing hydrophilic quaternary ammonium salt groups into chitosan. It has typical quaternary ammonium salt properties, such as antibacterial, bacteriostatic, hygroscopic, and moisturizing properties, while maintaining the good adhesion and high permeability of chitosan.
[0019] Furthermore, the carboxylated chitosan N-carboxymethyl chitosan and / or N,O-carboxymethyl chitosan have better biochemical and physical properties, stronger adhesion, better solubility, and wider applications in biomedicine and biomaterials.
[0020] In one embodiment of the present invention, the mass percentage of fragrance in the foam-type cationic nanoemulsion hair growth liquid is 0.01%-1%.
[0021] A second objective of this invention is to provide a foam-type cationic nanoemulsion hair growth solution prepared by the method described above.
[0022] The technical solution of the present invention has the following advantages compared with the prior art:
[0023] The preparation method described in this invention encapsulates a positively charged chitosan derivative on the surface of a nanoemulsion, thus preparing a foam-type cationic nanoemulsion delivery carrier. This reverses the charge of the negatively charged nanoemulsion, allowing it to interact better with epidermal cells, reducing transdermal drug permeation, and increasing drug retention in the skin. Simultaneously, the chitosan derivative possesses strong permeability and adhesion, synergistically enhancing drug retention in the skin with the foaming agent, prolonging drug retention time in the body, increasing the duration of drug penetration, and better exerting local effects. Attached Figure Description
[0024] To make the content of this invention easier to understand, the invention will be further described in detail below with reference to specific embodiments and accompanying drawings, wherein:
[0025] Figure 1 This is a foam appearance diagram of Test Example 1 of the present invention;
[0026] Figure 2 This is a graph showing the in vitro transdermal penetration results of the hair growth solution and commercially available minoxidil tincture in Comparative Examples 2 and 3 and Example 2 of Test Example 3 of the present invention;
[0027] Figure 3 This is a diagram showing the results of the external transdermal penetration of the hair growth liquid in Comparative Example 4 and Example 4 of Test Example 3 of the present invention;
[0028] Figure 4 This is a graph showing the cumulative drug retention on the skin of the hair growth solution and commercially available minoxidil tincture in Test Example 3 of the present invention;
[0029] Figure 5 The image shows the effect of the hair growth liquid and commercially available minoxidil tincture in promoting hair growth on the back of mice in Test Example 4 of this invention.
[0030] Figure 6 The statistical analysis results show the effects of the hair growth liquid of Test Example 4 of this invention and commercially available minoxidil tincture on promoting hair growth on the back of mice.
[0031] Figure 7 This is a scanning electron microscope image of newly grown hair on the back of a mouse in Test Example 4 of the present invention. Detailed Implementation
[0032] The present invention will be further described below with reference to the accompanying drawings and specific embodiments, so that those skilled in the art can better understand and implement the present invention. However, the embodiments described are not intended to limit the present invention.
[0033] Example 1
[0034] The foam-type cationic nanoemulsion hair growth liquid and its preparation method of the present invention specifically include the following steps:
[0035] 2.4 g of polyethylene glycol glycerol octanoate, 0.27 g of polyglycerol-3 oleate, 0.05 g of medium-chain triglycerides, 0.8 g of propylene glycol, 0.05 g of phenoxyethanol, and 0.01 g of methylparaben were weighed and mixed by heating and stirring at 60 °C for 5 min. Then, 0.1 g of minoxidil was added to the mixture, and the mixture was heated and stirred at the same temperature for 0.5 h to ensure complete dissolution. Finally, the mixture was added dropwise to 6.31 g of 0.1 wt% HACCP aqueous solution under stirring at room temperature, and 0.01 g of fragrance was added to obtain a foam-type cationic nanoemulsion hair growth solution.
[0036] Example 2
[0037] The foam-type cationic nanoemulsion hair growth liquid and its preparation method of the present invention specifically include the following steps:
[0038] 2.4 g of polyethylene glycol glycerol octanoate, 0.27 g of polyglycerol-3 oleate, 0.05 g of medium-chain triglycerides, 0.8 g of propylene glycol, 0.05 g of phenoxyethanol, and 0.01 g of methylparaben were weighed and mixed by heating and stirring at 60 °C for 5 min. Then, 0.1 g of minoxidil was added to the mixture, and the mixture was heated and stirred at the same temperature for 0.5 h to ensure complete dissolution. Finally, the mixture was added dropwise to 6.31 g of 0.5 wt% HACCP aqueous solution under stirring at room temperature, and 0.01 g of fragrance was added to obtain a foam-type cationic nanoemulsion hair growth solution.
[0039] Example 3
[0040] The foam-type cationic nanoemulsion hair growth liquid and its preparation method of the present invention specifically include the following steps:
[0041] 2.4 g of polyethylene glycol glycerol octanoate, 0.27 g of polyglycerol-3 oleate, 0.05 g of medium-chain triglycerides, 0.8 g of propylene glycol, 0.05 g of phenoxyethanol, and 0.01 g of methylparaben were weighed and mixed by heating and stirring at 60 °C for 5 min. Then, 0.1 g of minoxidil was added to the mixture, and the mixture was heated and stirred at the same temperature for 0.5 h to ensure complete dissolution. Finally, the mixture was added dropwise to 6.31 g of 1 wt% HACCP aqueous solution under stirring at room temperature, and 0.01 g of fragrance was added to obtain a foam-type cationic nanoemulsion hair growth solution.
[0042] Example 4
[0043] The foam-type cationic nanoemulsion hair growth liquid and its preparation method of the present invention specifically include the following steps:
[0044] Weigh out 2.4g of polyethylene glycol glycerol octanoate, 0.27g of polyglycerol-3 oleate, 0.05g of medium-chain triglycerides, 0.8g of propylene glycol, 0.05g of phenoxyethanol, and 0.01g of methylparaben. Mix these components by heating and stirring at 60°C for 5 minutes. Then, add 0.025g of finasteride to the mixture and heat and stir at the same temperature for 0.5 hours until fully dissolved. Finally, add the mixture dropwise to 6.385g of a 0.5wt% HACCP aqueous solution under stirring at room temperature, and add 0.01g of fragrance to obtain the hair growth solution.
[0045] Comparative Example 1
[0046] Weigh out 2.4g of octanoic acid-capric acid-decalcium polyethylene glycol glyceride, 0.27g of polyglycerol-3 oleate, 0.05g of medium-chain triglycerides, 0.8g of propylene glycol, 0.05g of phenoxyethanol, and 0.01g of methylparaben. Heat and stir at 60℃ for 5 minutes to mix. Then, add the mixture dropwise to 6.41g of water under stirring at room temperature, and add 0.01g of fragrance to obtain the hair growth liquid.
[0047] Comparative Example 2
[0048] Weigh out 2.4g of polyethylene glycol glycerol octanoate, 0.27g of polyglycerol-3 oleate, 0.05g of medium-chain triglycerides, 0.4g of propylene glycol, 0.05g of phenoxyethanol, and 0.01g of methylparaben. Mix them by heating and stirring at 60℃ for 5 minutes. Then add 0.1g of minoxidil to the mixture and heat and stir at the same temperature for 0.5 hours until fully dissolved. Finally, add the mixture dropwise to 6.71g of water under stirring at room temperature, and add 0.01g of fragrance to obtain the hair growth solution.
[0049] Comparative Example 3
[0050] Weigh out 2.4g of polyethylene glycol glycerol octanoate, 0.27g of polyglycerol-3 oleate, 0.05g of medium-chain triglycerides, 0.8g of propylene glycol, 0.05g of phenoxyethanol, and 0.01g of methylparaben. Mix them by heating and stirring at 60℃ for 5 minutes. Then add 0.1g of minoxidil to the mixture and heat and stir at the same temperature for 0.5 hours until fully dissolved. Finally, add the mixture dropwise to 6.31g of water under stirring at room temperature, and add 0.01g of fragrance to obtain the hair growth solution.
[0051] Comparative Example 4
[0052] Weigh out 2.4g of polyethylene glycol glycerol octanoate / capric acid, 0.27g of polyglycerol-3 oleate, 0.05g of medium-chain triglycerides, 0.8g of propylene glycol, 0.05g of phenoxyethanol, and 0.01g of methylparaben. Mix them by heating and stirring at 60℃ for 5 minutes. Then add 0.025g of finasteride to the mixture and heat and stir at the same temperature for 0.5 hours until fully dissolved. Finally, add the mixture dropwise to 6.385g of water under stirring at room temperature, and add 0.01g of fragrance to obtain the hair growth solution.
[0053] Comparative Example 5
[0054] Weigh out 2.4g of octanoic acid-capric acid-decalcium polyethylene glycol glyceride, 0.27g of polyglycerol-3 oleate, 0.05g of medium-chain triglycerides, 0.8g of propylene glycol, 0.05g of phenoxyethanol, and 0.01g of methylparaben. Heat and stir at 60℃ for 5 minutes to mix. Then, under stirring at room temperature, add the mixture dropwise to 6.41g of 0.5wt% HACC aqueous solution and add 0.01g of fragrance to obtain the hair growth liquid.
[0055] Test Example 1: Foam Appearance Diagram
[0056] The appearance of the foam after the hair growth liquid of Examples 1-4 and Comparative Examples 2-5 is extruded by a power pump, as shown in the following figures. Figure 1 As shown. From Figure 1 It can be seen that the hair growth liquids prepared in the various embodiments and comparative examples have good foaming properties and stability after being extruded by a power pump. Among their components, caprylic and capric acid polyethylene glycol glyceride has excellent foaming ability. The foam can allow the drug and functional ingredients to be in contact with the lesion for a long time, promote the deep penetration of the drug and functional ingredients into the scalp, prolong the retention time of the drug in the body, and improve the efficacy.
[0057] Test Example 2: Nanoemulsion particle size, PDI, and Zeta potential
[0058] Take appropriate amounts of the hair growth solutions prepared in Examples 1-4 and Comparative Examples 2-5, and measure the particle size, PDI, and Zeta potential using a nanoparticle size and Zeta potential analyzer. The above experiments were performed three times, and the average value was taken. The results are shown in Table 1.
[0059] Table 1
[0060] Group Average particle size ±SD / nm PDI Zeta potential ±SD / mV Example 1 49.04±0.640 0.369±0.006 +33.2±3.30 Example 2 46.33±0.100 0.283±0.040 +52.8±2.20 Example 3 50.20±0.300 0.357±0.022 +58.6±2.20 Example 4 53.97±1.466 0.430±0.029 +32.9±1.47 Comparative Example 2 23.61±1.517 0.349±0.073 -14.5±2.11 Comparative Example 3 18.67±0.760 0.190±0.035 -12.0±1.33 Comparative Example 4 25.45±1.489 0.250±0.030 -15.1±1.31 Comparative Example 5 37.37±1.867 0.429±0.038 +10.2±1.12
[0061] As shown in Table 1, all hair growth liquid formulations were clear and transparent, with particle sizes less than 100 nm. The HACC-modified nanoemulsions exhibited increased particle size and a change in electrical potential from negative to positive. Larger nanoemulsion particle sizes reduce drug penetration into the bloodstream, resulting in more effective retention in the skin, especially in hair follicles. Furthermore, the positively charged nanoemulsions can interact better with epidermal cells, promoting drug retention in the skin.
[0062] Test Example 3: Evaluation of in vitro transdermal permeability and skin retention
[0063] Transdermal experiments were conducted using the Franz diffusion cell method: 30% ethanol-PBS solution was selected as the receiving cell medium. Appropriately sized pieces of skin were cut and fixed onto the diffusion cell filled with the receiving medium, with the stratum corneum facing upwards towards the drug delivery cell, ensuring close contact with the drug. The dermis faced downwards towards the receiving cell. Commercially available minoxidil tincture solutions were added to the drug delivery cell, along with the experimental group solutions. The experimental group solutions included hair growth solutions prepared in Comparative Examples 2, 3, and 4, as well as Examples 2 and 4. The rotation speed was set at 400 rpm, and the temperature at 37 ± 0.2℃. 1 mL samples were taken at 1 h, 2 h, 4 h, 6 h, 8 h, 10 h, 12 h, and 24 h after drug delivery, and an equal volume of receiving medium at the same temperature was immediately added. After filtration through a 0.22 μm microporous membrane, the drug content was determined by HPLC. The results are shown below. Figure 2-4 As shown.
[0064] from Figure 2-4 It can be seen that the cumulative drug permeation of HACC-modified nanoemulsions decreases while the amount retained in the skin increases. This is mainly because the increased particle size of HACC-modified nanoemulsions makes it more difficult for the drug to penetrate into the bloodstream, thus allowing the drug to be more effectively retained in the skin. Simultaneously, because HACC carries a positive charge, it can interact better with epidermal cells. HACC also has good adhesive properties, enhancing mucosal adhesion and increasing the time for drug penetration, further improving drug retention in the skin. Therefore, HACC-modified nanoemulsions can allow more drugs to act inside the skin, resulting in better local effects.
[0065] Test Example 4: In vivo pharmacodynamic evaluation
[0066] Ten male C57BL / 6 mice were selected, anesthetized with ether, and their backs were shaved before depilatory cream was applied. A mouse model of androgenetic alopecia was established by daily topical application of testosterone ethanol solution. Mice were randomly divided into five groups: a blank control group, a model group, a positive control group, and an experimental group. The positive control group received 100 μL of commercially available 5% minoxidil tincture, while the experimental group received 0.1 mg of the hair growth solution prepared in Comparative Examples 1, 3, 5, and Example 2. The medication was administered once daily for 19 consecutive days, starting on the first day after hair removal. Daily photographs were taken to record hair growth on the backs of the mice. The results are shown below. Figure 5 As shown; and a statistical analysis was performed on the effect of promoting hair growth on the back of mice, the results of which are as follows. Figure 6 As shown; scanning electron microscope image of hair as shown. Figure 7 As shown.
[0067] from Figure 5It can be seen that on day 19, the back skin of mice treated in the experimental group showed more and denser hair growth compared to the model group, indicating that the cationic nanoemulsion foam has a hair growth promoting effect. Comparative examples 1 and 5, which do not contain drugs, also showed a hair growth promoting effect, possibly because active ingredients such as caprylic / capric acid PEG-glycerol and medium-chain triglycerides have anti-inflammatory, antioxidant, and lipid metabolism regulating functions, reducing the oxidative stress level and inflammatory factor level in the hair follicle microenvironment, thereby improving the hair follicle microenvironment and promoting hair growth. The HACC-modified examples showed better results than the comparative examples. Besides the modified nanoemulsion improving the skin retention of related functional ingredients and drugs, the antibacterial and anti-inflammatory effects of the HACC itself synergistically improved hair growth with the foam. (See the image of mouse back hair on day 19). Figure 5 ), Statistical analysis results ( Figure 6 ) and scanning electron microscope images of hair ( Figure 7 As can be seen, the 1% minoxidil foam prepared in Example 2, even at lower dosages, showed comparable hair growth effects to the mice treated with the commercially available 5% minoxidil tincture, with no significant differences in hair length, weight, or diameter. The mice treated with the minoxidil-free foam prepared in Comparative Example 5 showed weaker effects than those in Example 2 because their skin turned gray later, but they still had a certain effect on promoting hair growth.
[0068] Obviously, the above embodiments are merely illustrative examples for clear explanation and are not intended to limit the implementation. Those skilled in the art will recognize that other variations or modifications can be made based on the above description. It is neither necessary nor possible to exhaustively list all possible implementations here. However, obvious variations or modifications derived therefrom are still within the scope of protection of this invention.
Claims
1. A method for preparing a foam-type cationic nanoemulsion hair growth liquid, characterized in that, Includes the following steps, S1. Mix the surfactant, oil phase material, co-surfactant and antibacterial agent evenly, add the drug, heat to dissolve it completely, and obtain the oil phase. The surfactant is polyethylene glycol glycerol caprylate and polyglycerol-3 oleate, wherein the oil phase contains 5%-70% polyethylene glycol glycerol caprylate and 0.5%-20% polyglycerol-3 oleate by mass. The oil phase material is a medium-chain triglyceride, and the mass percentage of medium-chain triglycerides in the oil phase is 0.1%-10%. The co-surfactant is propylene glycol, and the mass percentage of propylene glycol in the oil phase is 1%-50%. The antibacterial agent is phenoxyethanol and methylparaben, wherein the mass percentage of phenoxyethanol in the oil phase is 0.01%-5% and the mass percentage of methylparaben is 0.01%-5%. The drug is finasteride and / or minoxidil, and the mass percentage of the drug in the oil phase is 0.1%-5%. S2. The oil phase described in S1 is added dropwise to the aqueous phase, and fragrance is added to obtain the foam-type cationic nanoemulsion hair growth liquid; the aqueous phase includes chitosan derivative and water; the chitosan derivative is hydroxypropyltrimethylammonium chloride chitosan; the mass percentage of hydroxypropyltrimethylammonium chloride chitosan in the aqueous phase is 0.1%-1%; the mass percentage of fragrance in the foam-type cationic nanoemulsion hair growth liquid is 0.01%-1%; the mass ratio of the oil phase to the aqueous phase is 1-2:3-4.
2. The preparation method of the foam-type cationic nanoemulsion hair growth liquid according to claim 1, characterized in that, In S1, the heating temperature is 40℃-70℃.
3. A foam-type cationic nanoemulsion hair growth solution prepared by the method according to any one of claims 1-2.