A hair loss prevention nano-composition and a method for preparing the same

Abstract

The application belongs to the technical field of carriers, and particularly relates to a hair loss prevention nano composition and a preparation and application thereof. The hair loss prevention nano composition comprises the following components in percentage by weight: 0.2-2% of hydrophilic modified starch, 1-14% of hair loss prevention hydrophobic active ingredient, 0.1-10% of emulsifier, 0.1-10% of stabilizer, 20-50% of organic solvent, and 10-78.1% of water; the hair loss prevention hydrophobic active ingredient comprises a minoxidil-like compound. The application further provides a preparation method of the hair loss prevention nano composition, and the prepared hair loss prevention nano composition has good transdermal permeability and hair loss prevention treatment effect. In addition, compared with a method of using a surfactant for solubilization or using anhydrous ethanol for solubilization in the prior art, the prepared nano composition has a better hair loss prevention treatment effect, is less irritating to human skin, and has better skin permeability.

Description

Technical Field

[0001] This invention belongs to the field of carrier technology, and in particular relates to an anti-hair loss nanocomposition and its preparation method. Background Technology

[0002] Hair loss can be classified into androgenetic alopecia (or seborrheic alopecia), neurogenic alopecia, chemical alopecia, senile alopecia, and pathological alopecia, among which androgenetic alopecia is currently the most common cause of hair loss in clinical practice.

[0003] In the treatment of androgenetic alopecia, oral administration of drugs such as finasteride, dutasteride, and minoxidil is commonly used clinically. However, long-term use of these drugs can easily lead to adverse reactions. Minoxidil-like compounds are a class of compounds synthesized by chemically modifying the chemical structure of minoxidil, such as diaminopyrimidine oxide and pyrrolidine diaminopyrimidine oxide. Their anti-hair loss and hair growth efficacy is comparable to minoxidil, but they are milder and are often used in anti-hair loss shampoos and conditioners. In the transdermal drug delivery treatment of androgenetic alopecia, follicular delivery of the anti-hair loss active ingredient is crucial. Minoxidil-like compounds have low water solubility and poor skin penetration; to promote transdermal and follicular delivery, they are often dissolved in alcohol to prepare tinctures. However, alcohol is highly irritating and can easily cause scalp discomfort during use. Summary of the Invention

[0004] The purpose of this invention is to overcome the shortcomings of the prior art and provide a composition with anti-hair loss effect and its preparation method. The anti-hair loss nanocomposition of this invention can improve the water solubility and skin permeability of the anti-hair loss active ingredients minoxidil and ceramide, and can effectively promote hair follicle delivery performance.

[0005] To achieve the above objectives, the technical solution adopted by the present invention is as follows:

[0006] In a first aspect, the present invention provides a nanocomposition for preventing hair loss, comprising the following components by weight percentage: 0.2-2% hydrophilic modified starch, 1-14% hydrophobic active ingredient for preventing hair loss, 0.1-10% emulsifier, 0.1-10% stabilizer, 20-50% organic solvent, and 10-78.1% water; wherein the hydrophobic active ingredient for preventing hair loss includes a minoxidil-like compound.

[0007] Modified starch, used as a carrier wall material, possesses a hydrophobic core and a hydrophilic shell, enabling the encapsulation of minoxidil compounds, the active ingredient for preventing hair loss. The hydrophobic active ingredient is encapsulated within the hydrophobic core of the modified starch, improving the water solubility and skin penetration of minoxidil. Thanks to its unique core-shell structure, the hydrophobic micelle core provides a loading site for the hydrophobic active ingredient through hydrophobic-hydrophobic interactions, thus solubilizing and embedding it. The hydrophilic micelle shell promotes the water solubility of the nanocarrier while also acting as a protective layer to maintain its stability.

[0008] Compared with minoxidil compounds, the anti-hair loss nanocomposition of the present invention exhibits better transdermal penetration and superior anti-hair loss treatment effect.

[0009] The components of the anti-hair loss nanocomposition are within the scope of this invention. The prepared anti-hair loss nanocomposition has good transdermal permeability and anti-hair loss therapeutic effect, and low irritation to human skin.

[0010] Preferably, the hydrophilic modified starch is diethylaminoethyl methacrylate modified starch or 2-methacryloyloxyethylphosphonic choline modified starch.

[0011] Compared with existing methods that use surfactants or anhydrous ethanol for solubilization (i.e., tinctures in the prior art), this invention uses modified starch material to encapsulate hydrophobic active ingredients for hair loss prevention. The resulting anti-hair loss nanocomposition has low skin irritation, good skin permeability, and excellent anti-hair loss treatment effect, and can be applied to hair care products.

[0012] The method for preparing the hydrophilic modified starch is as follows:

[0013] (1) Add starch to organic solvent A and stir at 60-100℃ for 2-8 hours to completely dissolve the starch in organic solvent A to obtain a starch solution;

[0014] (2) Under the protection of an inert gas, add a brominating agent to the starch solution obtained in step (1) and react at 10-45℃ for 12-72h to obtain brominated starch.

[0015] (3) Diethylaminoethyl methacrylate / 2-methacryloyloxyethyl phosphorylcholine, the brominated starch obtained in step (2), and N,N,N',N”,N”-pentamethyldiethylenetriamine are dissolved in organic solvent A. Under inert gas protection, a catalyst is added to the reaction system and the reaction is carried out at 40-80℃ for 12-48h.

[0016] (4) The catalyst was removed by elution. After the eluent was concentrated, organic solvent B was added to the concentrate to precipitate the solid product. The solid product was collected and dried to obtain the hydrophilic modified starch.

[0017] Preferably, the brominating agent is 2-bromoisobutyryl bromide; organic solvent A includes at least one of dimethyl sulfoxide, dichloromethane, chloroform, tetrahydrofuran, and N,N-dimethylformamide; organic solvent B includes at least one of n-hexane, petroleum ether, diethyl ether, and ethyl acetate.

[0018] In step (4), organic solvent B acts as a precipitant.

[0019] Preferably, the starch is amylose; the number-average molecular weight of the starch is 50,000-70,000; the structure of the hydrophilic modified starch is as follows:

[0020]

[0021] The diethylaminoethyl methacrylate or 2-methacryloyloxyethyl phosphorylcholine is grafted onto the glucose molecule-[6]-hydroxyl group of starch; the theoretical grafting rate is 25-100%.

[0022] Preferably, the minoxidil-like compound comprises at least one of pyrrolidinyl diaminopyrimidine oxide and diaminopyrimidine oxide.

[0023] Preferably, the mass ratio of the pyrrolidinyl diaminopyrimidine oxide to the diaminopyrimidine oxide is 1:(1-5).

[0024] More preferably, the mass ratio of the pyrrolyl diaminopyrimidine oxide to the diaminopyrimidine oxide is 1:3.

[0025] The ratio of pyrrolyl diaminopyrimidine oxide and diaminopyrimidine oxide affects the particle size and encapsulation efficiency of the final product. In anti-hair loss nanocomposites, compared to encapsulating either pyrrolyl diaminopyrimidine oxide or diaminopyrimidine oxide as a single component, the co-encapsulation of pyrrolyl diaminopyrimidine oxide and diaminopyrimidine oxide with modified starch results in a higher encapsulation efficiency for the anti-hair loss active ingredient. Specifically, when the ratio of pyrrolyl diaminopyrimidine oxide to diaminopyrimidine oxide is 1:3, the sample exhibits the smallest particle size and the highest encapsulation efficiency of the anti-hair loss active ingredient, reaching 97.2%.

[0026] Preferably, the anti-hair loss hydrophobic active ingredient further includes ceramide, wherein the ceramide is present in the anti-hair loss nanocomposition at a weight percentage of 0.5-4%.

[0027] Adding ceramides to hair loss treatments for scalp repair effectively combines treatment and scalp care, resulting in better hair loss prevention. Therefore, combining minoxidil-like compounds with ceramides in hair loss prevention treatments, addressing both hair loss prevention and scalp barrier repair, can fundamentally solve the problem of hair loss.

[0028] Preferably, the ceramide is at least one of ceramide E, ceramide EOH, ceramide EOP, ceramide AP, ceramide AS, ceramide AH, ceramide NP, ceramide ND, and ceramide NH.

[0029] Preferably, the emulsifier includes at least one of soybean lecithin, hydrogenated soybean lecithin, dipalmitoylphosphatidylcholine, egg yolk lecithin, PEG-40 hydrogenated castor oil, PEG-60 hydrogenated castor oil, cocoyl glucoside, and polyglycerol-10 laurate; the stabilizer includes at least one of cholesterol, phytosterols, glyceryl monooleate, and sodium cholate; and the organic solvent includes at least one of 1,3-propanediol, glycerol, 1,4-butanediol, pentanediol, 1,2-hexanediol, dipropylene glycol, diethylene glycol, octyl dodecanol, octyl / decyl triglyceride, dichloromethane, acetone, tetrahydrofuran, and dimethyl sulfoxide.

[0030] Secondly, the present invention provides a method for preparing the above-mentioned anti-hair loss nanocomposition, comprising the following steps:

[0031] (1) Dissolve the hydrophilic modified starch, anti-hair loss hydrophobic active ingredient, emulsifier and stabilizer in an organic solvent, heat and stir to dissolve, and obtain phase A solution;

[0032] (2) When the hydrophilic modified starch is modified starch with diethylaminoethyl methacrylate (DEAEMA), the hydrophobic active ingredient for preventing hair loss is a minoxidil-like compound. The A phase solution is added dropwise to an acidic solution. After the addition is complete, stirring is continued to obtain a mixed solution. When the hydrophilic modified starch is modified starch with 2-methacryloyloxyethyl phosphorylcholine (MPC), the hydrophobic active ingredient for preventing hair loss is a minoxidil-like compound and a ceramide. The A phase solution is added dropwise to water. After the addition is complete, stirring is continued to obtain a mixed solution.

[0033] (3) The mixed solution is subjected to nano-processing to obtain a composition with anti-hair loss effect.

[0034] In the anti-hair loss nanocomposite, the terminal amino groups of the grafted segments on the modified starch need to be protonated under suitable acidic conditions to become hydrophilic. If the solution system is not in a suitable acidic environment, the modified starch cannot effectively self-assemble into a nanocarrier. In an acidic medium, DEAEMA can be protonated and become hydrophilic. Under these conditions, polyacrylate-modified starch can self-assemble into micelle structures, encapsulating minoxidil-like compounds to form the anti-hair loss nanocomposite.

[0035] In the anti-hair loss and repair composition, the grafted chain segment MPC on the modified starch is hydrophilic, so there is no need to adjust the pH value of the solution system.

[0036] Preferably, the heating temperature is 40-80℃; the stirring speed is 50-500 rpm; and the stirring time is 20-60 min.

[0037] Preferably, the dropping rate is 1-10 mL / min; the stirring speed is 50-500 rpm; and the stirring time is 20-60 min.

[0038] Preferably, the stirring method is mechanical stirring or magnetic stirring.

[0039] Preferably, the above preparation method satisfies at least one of the following (a) to (d):

[0040] (a) The acidic solution is obtained by dissolving a pH adjuster in water; the pH adjuster accounts for 5-15% by weight in the acidic solution;

[0041] (b) The pH of the acidic solution is 3-6;

[0042] (c) The nano-sizing process includes shear dispersion treatment and microfluidic homogenization treatment;

[0043] (d) The shearing and dispersion treatment is performed by shearing at 8000-12000 rpm for 10-60 min; the homogenization pressure of the microjet homogenization treatment is 50-120 MPa, and the number of homogenization cycles is 1-8.

[0044] Preferably, the pH adjuster includes at least one of citric acid, oxalic acid, and acetic acid.

[0045] Preferably, the high-speed shear dispersion treatment is performed by shear homogenization using a high-speed shear homogenizer; the microfluidic homogenization treatment is performed by homogenization using a microfluidic homogenizer.

[0046] Compared with the prior art, the present invention has the following beneficial effects:

[0047] The copolymers formed by graft copolymerization of starch and synthetic organic monomers possess properties of both natural and synthetic polymers, making them ideal materials for manufacturing many useful products. This invention uses diethylaminoethyl methacrylate or 2-methacryloyloxyethylphosphorylcholine-modified linear starch as the encapsulating agent in the composition. Different modified starches are required for encapsulation depending on the active ingredient. When the hydrophilic modified starch is diethylaminoethyl methacrylate-modified, the hydrophobic active ingredient for preventing hair loss is a minoxidil-like compound; when the hydrophilic modified starch is 2-methacryloyloxyethylphosphorylcholine-modified, the hydrophobic active ingredients for preventing hair loss are a minoxidil-like compound and ceramides. The resulting anti-hair loss nanocompositions exhibit high encapsulation efficiency and small particle size. Using ceramides for scalp repair effectively combines hair loss treatment with scalp repair, achieving a better therapeutic effect in preventing hair loss.

[0048] Compared to minoxidil-like compounds, the anti-hair loss nanocomposition of the present invention exhibits better transdermal penetration and superior anti-hair loss treatment effect. Furthermore, compared to methods using surfactants or anhydrous ethanol for solubilization in the prior art (i.e., tinctures in the prior art), the present invention uses modified starch to encapsulate the anti-hair loss active ingredients, resulting in an anti-hair loss nanocomposition with lower skin irritation, better skin penetration, and superior anti-hair loss treatment effect. Detailed Implementation

[0049] To better illustrate the purpose, technical solution, and advantages of the present invention, the present invention will be further described below in conjunction with specific embodiments.

[0050] Unless otherwise specified in the examples, the conditions should be performed under standard conditions or conditions recommended by the manufacturer. Reagents or instruments whose manufacturers are not specified are all commercially available products. Unless otherwise specified, all reagents used in the examples can be purchased from the market. In the embodiments of this invention, the amylose raw material and the ATRP reactive polymerization monomers DMAEMA and MPC can be purchased directly from Shanghai Aladdin Biochemical Technology Co., Ltd.

[0051] The full names of all abbreviations appearing in the text are as follows:

[0052] ATRP reaction: Atom Transfer Radical Polymerization

[0053] Amylose: linear starch

[0054] DEAEMA: Diethylaminoethyl methacrylate

[0055] MPC: 2-Methylacryloxyethylphosphocholine

[0056] Example 1

[0057] An anti-hair loss nanocomposition according to an embodiment of the present invention comprises the following components by weight percentage: 1% hydrophilic modified starch, 6% minoxidil-like compound, 0.8% emulsifier, 0.2% stabilizer, 30% organic solvent, and 62% water.

[0058] The hydrophilic modified starch is Amylose-g-DEAEMA modified starch, which is modified with diethylaminoethyl methacrylate (DEAEMA).

[0059] The starch is amylose, and the number-average molecular weight of the starch is 55418.

[0060] The structure of the hydrophilic modified starch is as follows:

[0061]

[0062] The diethylaminoethyl methacrylate is grafted onto the glucose molecule-[6]-hydroxyl group of starch; the theoretical grafting rate is 300 / 308 = 97.4%; the molecular weight of the Amylose-g-DEAEMA is 110154.

[0063] The minoxidil-like compound consists of pyrrolidine diaminopyrimidine oxide and diaminopyrimidine oxide.

[0064] The mass ratio of the pyrrolyl diaminopyrimidine oxide to the diaminopyrimidine oxide is 1:3.

[0065] The emulsifier is soybean lecithin; the stabilizer is phytosterol; and the organic solvent is 1,3-propanediol.

[0066] The preparation method of the hair loss prevention nanocomposition includes the following steps:

[0067] By weight percentage, 1% of modified starch Amylose-g-DEAEMA, 1.5% of pyrrolidine diaminopyrimidine oxide, 4.5% of diaminopyrimidine oxide, 0.8% of soybean lecithin, and 0.2% of phytosterol were dissolved in 30% 1,3-propanediol. The solution was heated to 50°C and stirred at 300 rpm for 30 min until the raw materials were uniformly mixed. After the raw materials were fully dissolved, the solution was cooled to room temperature to obtain phase A. The pH of deionized water was adjusted with citric acid to prepare an acidic solution with a pH of 5.00. Phase A solution was added dropwise to the 62% acidic solution at a rate of 5 mL / min. After the addition was completed, the solution was stirred at 400 rpm for 30 min. The solution was dispersed by high-speed shearing (11000 rpm) for 15 min, and then subjected to high-pressure microfluidic treatment at a homogenization pressure of 70 MPa for 4 homogenization cycles to prepare the anti-hair loss nanocomposition.

[0068] Example 2

[0069] The hair loss prevention nanocomposition of this invention differs from that of Example 1 in that the 62% by weight of the acidic solution with pH 5.00 in Example 1 is replaced with a 62% by weight of the acidic solution with pH 3.00, while the rest remains unchanged, to prepare the hair loss prevention nanocomposition.

[0070] Example 3

[0071] The hair loss prevention nanocomposition of this invention differs from that of Example 1 in that the 62% by weight of the acidic solution with pH 5.00 in Example 1 is replaced with a 62% by weight of the acidic solution with pH 4.00, while the rest remains unchanged, to prepare the hair loss prevention nanocomposition.

[0072] Example 4

[0073] The hair loss prevention nanocomposition of this invention differs from that of Example 1 in that the 62% by weight of the acidic solution with pH 5.00 in Example 1 is replaced with a 62% by weight of the acidic solution with pH 6.00, while the rest remains unchanged, to prepare the hair loss prevention nanocomposition.

[0074] Example 5

[0075] The hair loss prevention nanocomposition of this invention differs from that of Example 1 in that: 1.5% by weight of pyrrolidinyl diaminopyrimidine oxide and 4.5% by weight of diaminopyrimidine oxide in Example 1 are replaced with 6% by weight of pyrrolidinyl diaminopyrimidine oxide, while the rest remain unchanged, to prepare the hair loss prevention nanocomposition.

[0076] Example 6

[0077] The hair loss prevention nanocomposition of this invention differs from that of Example 1 in that: the 1.5% by weight of pyrrolidinyl diaminopyrimidine oxide and the 4.5% by weight of diaminopyrimidine oxide in Example 1 are replaced with 3% by weight of pyrrolidinyl diaminopyrimidine oxide and 3% by weight of diaminopyrimidine oxide, while the rest remain unchanged, thus preparing the hair loss prevention nanocomposition.

[0078] Example 7

[0079] The hair loss prevention nanocomposition of this invention differs from that of Example 1 in that: the 1.5% by weight of pyrrolidinyl diaminopyrimidine oxide and the 4.5% by weight of diaminopyrimidine oxide in Example 1 are replaced with 2% by weight of pyrrolidinyl diaminopyrimidine oxide and 4% by weight of diaminopyrimidine oxide, while the rest remain unchanged, to prepare the hair loss prevention nanocomposition.

[0080] Example 8

[0081] The hair loss prevention nanocomposition of this invention differs from that of Example 1 in that: the 1.5% by weight of pyrrolidinyl diaminopyrimidine oxide and the 4.5% by weight of diaminopyrimidine oxide in Example 1 are replaced with 1.2% by weight of pyrrolidinyl diaminopyrimidine oxide and the 4.8% by weight of diaminopyrimidine oxide, while the rest remain unchanged, to prepare the hair loss prevention nanocomposition.

[0082] Example 9

[0083] The hair loss prevention nanocomposition of this invention differs from that of Example 1 in that: the 1.5% by weight of pyrrolidinyl diaminopyrimidine oxide and the 4.5% by weight of diaminopyrimidine oxide in Example 1 are replaced with 1% by weight of pyrrolidinyl diaminopyrimidine oxide and 5% by weight of diaminopyrimidine oxide, while the rest remain unchanged, thus preparing the hair loss prevention nanocomposition.

[0084] Example 10

[0085] The hair loss prevention nanocomposition of this invention differs from that of Example 1 in that: 1.5% by weight of pyrrolidinyl diaminopyrimidine oxide and 4.5% by weight of diaminopyrimidine oxide in Example 1 are replaced with 6% by weight of diaminopyrimidine oxide, while the rest remain unchanged, to prepare the hair loss prevention nanocomposition.

[0086] Example 11

[0087] The hair loss prevention nanocomposition of this invention differs from that of Example 1 in that the modified starch Amylose-g-DEAEMA, which accounts for 1% by weight in Example 1, is replaced with modified starch Amylose-g-DEAEMA, which accounts for 0.2% by weight, while the rest remains unchanged, to prepare the hair loss prevention nanocomposition.

[0088] Example 12

[0089] The hair loss prevention nanocomposition of this invention differs from that of Example 1 in that the modified starch Amylose-g-DEAEMA with a weight percentage of 1% in Example 1 is replaced with modified starch Amylose-g-DEAEMA with a weight percentage of 0.5%, while the rest remains unchanged, and the hair loss prevention nanocomposition is prepared.

[0090] Example 13

[0091] The hair loss prevention nanocomposition of this invention differs from that of Example 1 in that the modified starch Amylose-g-DEAEMA with a weight percentage of 1% in Example 1 is replaced with modified starch Amylose-g-DEAEMA with a weight percentage of 1.5%, while the rest remains unchanged, and the hair loss prevention nanocomposition is prepared.

[0092] Example 14

[0093] The hair loss prevention nanocomposition of this invention differs from that of Example 1 in that the modified starch Amylose-g-DEAEMA with a weight percentage of 1% in Example 1 is replaced with modified starch Amylose-g-DEAEMA with a weight percentage of 2.0%, while the rest remains unchanged, and the hair loss prevention nanocomposition is prepared.

[0094] Example 15

[0095] An anti-hair loss nanocomposition according to an embodiment of the present invention comprises the following components by weight percentage: 1% hydrophilic modified starch, 6% minoxidil-like compound, 0.5% emulsifier, 0.3% stabilizer, 30% organic solvent, and 62.2% water.

[0096] The hydrophilic modified starch is Amylose-g-DEAEMA modified starch, which is modified with diethylaminoethyl methacrylate (DEAEMA).

[0097] The starch is amylose, and the number-average molecular weight of the starch is 55418.

[0098] The structure of the hydrophilic modified starch is as follows:

[0099]

[0100] The diethylaminoethyl methacrylate is grafted onto the glucose molecule-[6]-hydroxyl group of starch; the theoretical grafting rate is 300 / 308 = 97.4%; the molecular weight of the Amylose-g-DEAEMA is 110154.

[0101] The minoxidil-like compound consists of pyrrolidine diaminopyrimidine oxide and diaminopyrimidine oxide.

[0102] The mass ratio of the pyrrolyl diaminopyrimidine oxide to the diaminopyrimidine oxide is 1:3.

[0103] The emulsifier is dipalmitoylphosphatidylcholine; the stabilizer is cholesterol; and the organic solvent is pentylene glycol.

[0104] The preparation method of the hair loss prevention nanocomposition includes the following steps:

[0105] By weight percentage, 1% modified starch Amylose-g-DEAEMA, 1.5% pyrrolyl diaminopyrimidine oxide, 4.5% diaminopyrimidine oxide, 0.5% dipalmitoylphosphatidylcholine, and 0.3% cholesterol were dissolved in 30% pentanediol. The solution was heated to 40°C and stirred at 50 rpm for 60 min until the raw materials were uniformly mixed. After the raw materials were fully dissolved, the solution was cooled to room temperature to obtain phase A solution. The pH of deionized water was adjusted with citric acid to prepare an acidic solution with a pH of 5.00. Phase A solution was added dropwise to the 62.2% acidic solution at a rate of 1 mL / min. After the addition was completed, the solution was stirred at 500 rpm for 20 min. The solution was dispersed by high-speed shearing (6000 rpm) for 20 min, and then subjected to high-pressure microfluidic treatment at a homogenization pressure of 120 MPa for one homogenization cycle to prepare the anti-hair loss nanocomposition.

[0106] Example 16

[0107] An anti-hair loss nanocomposition according to an embodiment of the present invention comprises the following components by weight percentage: 1% hydrophilic modified starch, 6% minoxidil-like compound, 1.5% emulsifier, 0.5% stabilizer, 40% organic solvent, and 51% water.

[0108] The hydrophilic modified starch is Amylose-g-DEAEMA modified starch, which is modified with diethylaminoethyl methacrylate (DEAEMA).

[0109] The starch is amylose, and the number-average molecular weight of the starch is 55418.

[0110] The structure of the hydrophilic modified starch is as follows:

[0111]

[0112] The diethylaminoethyl methacrylate is grafted onto the glucose molecule-[6]-hydroxyl group of starch; the theoretical grafting rate is 300 / 308 = 97.4%; the molecular weight of the Amylose-g-DEAEMA is 110154.

[0113] The minoxidil-like compound consists of pyrrolidine diaminopyrimidine oxide and diaminopyrimidine oxide.

[0114] The mass ratio of the pyrrolyl diaminopyrimidine oxide to the diaminopyrimidine oxide is 1:3.

[0115] The emulsifier is egg yolk lecithin; the stabilizer is glyceryl monooleate; and the organic solvent is glycerol.

[0116] The preparation method of the hair loss prevention nanocomposition includes the following steps:

[0117] By weight percentage, 1% modified starch Amylose-g-DEAEMA, 1.5% pyrrolidine diaminopyrimidine oxide, 4.5% diaminopyrimidine oxide, 1.5% egg yolk lecithin, and 0.5% monooleate glyceryl were dissolved in 40% glycerol. The solution was heated to 80°C and stirred at 500 rpm for 20 minutes until the raw materials were evenly mixed. After the raw materials were fully dissolved, the solution was cooled to room temperature to obtain phase A solution. The pH of deionized water was adjusted with citric acid to prepare an acidic solution with a pH of 4.50. Phase A solution was added dropwise to the 51% acidic solution at a rate of 10 mL / min. After the addition was completed, the solution was stirred at 400 rpm for 30 minutes. The solution was dispersed by high-speed shearing (12000 rpm) for 10 minutes, and then subjected to high-pressure microfluidic treatment at a homogenization pressure of 50 MPa for 8 homogenization cycles to prepare the anti-hair loss nanocomposition.

[0118] Example 17

[0119] An anti-hair loss nanocomposition according to an embodiment of the present invention comprises the following components by weight percentage: 1% hydrophilic modified starch, 4% minoxidil-like compound, 2% ceramide, 0.5% emulsifier, 0.2% stabilizer, 30% organic solvent, and the balance being water.

[0120] The hydrophilic modified starch is 2-methacryloyloxyethyl phosphorylcholine (MPC) modified starch Amylose-g-MPC.

[0121] The starch is amylose; the number-average molecular weight of the starch is 55418.

[0122] The structure of the hydrophilic modified starch is as follows:

[0123]

[0124] The 2-methacryloyloxyethylphosphorylcholine is grafted onto the glucose molecule-[6]-hydroxyl group of starch; the theoretical grafting rate is 231 / 308 = 75%; the molecular weight of the Amylose-g-MPC is 141797.

[0125] The minoxidil-like compound is composed of pyrrolidine diaminopyrimidine oxide and diaminopyrimidine oxide; the mass ratio of the pyrrolidine diaminopyrimidine oxide and diaminopyrimidine oxide is 1:3.

[0126] The ceramide is ceramide E.

[0127] The emulsifier is soybean lecithin; the stabilizer is cholesterol; and the organic solvent is 1,3-propanediol.

[0128] The preparation method of the hair loss prevention nanocomposition includes the following steps:

[0129] By weight percentage, 1% modified starch Amylose-g-MPC, 1% pyrrolidine diaminopyrimidine oxide, 3% diaminopyrimidine oxide, 2% ceramide E, 0.5% soybean lecithin, and 0.2% cholesterol were dissolved in 30% 1,3-propanediol. The solution was heated to 50°C and stirred at 300 rpm for 30 min until the raw materials were uniformly mixed. After the raw materials were fully dissolved, the solution was cooled to room temperature to obtain the alcohol phase. The alcohol phase was added dropwise at a rate of 3 mL / min to a 62.3% aqueous solution. After the addition was complete, the solution was stirred at 400 rpm for 30 min. The solution was then dispersed by high-speed shearing (11000 rpm) for 15 min; followed by high-pressure microfluidic treatment at a homogenization pressure of 70 MPa for 4 homogenization cycles to prepare the anti-hair loss nanocomposition.

[0130] Example 18

[0131] The hair loss prevention nanocomposition of this embodiment differs from that of Example 17 in that the 2.0% by weight of ceramide E in Example 17 is replaced with 2.0% by weight of ceramide NH, while the rest remains unchanged, to prepare the hair loss prevention nanocomposition.

[0132] Example 19

[0133] The hair loss prevention nanocomposition of this embodiment differs from that of Example 17 in that the 2.0% by weight of ceramide E in Example 17 is replaced with 2.0% by weight of ceramide AH, while the rest remains unchanged, to prepare the hair loss prevention nanocomposition.

[0134] Example 20

[0135] The hair loss prevention nanocomposition of this embodiment differs from that of Example 17 in that the 2.0% by weight of ceramide E in Example 17 is replaced with 2.0% by weight of ceramide NP, while the rest remains unchanged, to prepare the hair loss prevention nanocomposition.

[0136] Example 21

[0137] The hair loss prevention nanocomposition of this embodiment differs from that of Example 17 in that the modified starch Amylose-g-MPC with a weight percentage of 1.0% in Example 17 is replaced with modified starch Amylose-g-MPC with a weight percentage of 0.2%, while the rest remains unchanged, and the hair loss prevention nanocomposition is prepared.

[0138] Example 22

[0139] The hair loss prevention nanocomposition of this embodiment differs from that of Example 17 in that the modified starch Amylose-g-MPC with a weight percentage of 1.0% in Example 17 is replaced with modified starch Amylose-g-MPC with a weight percentage of 2.0%, while the rest remains unchanged, and the hair loss prevention nanocomposition is prepared.

[0140] Example 23

[0141] The hair loss prevention nanocomposition of this embodiment differs from that of Example 17 in that the 2.0% by weight of ceramide E in Example 17 is replaced with 0.5% by weight of ceramide E, while the rest remains unchanged, to prepare the hair loss prevention nanocomposition.

[0142] Example 24

[0143] The hair loss prevention nanocomposition of this embodiment differs from that of Example 17 in that the 2.0% by weight of ceramide E in Example 17 is replaced with 4.0% by weight of ceramide E, while the rest remains unchanged, to prepare the hair loss prevention nanocomposition.

[0144] Example 25

[0145] An anti-hair loss nanocomposition according to an embodiment of the present invention comprises the following components by weight percentage:

[0146] The ingredients are: 1% hydrophilic modified starch, 4% minoxidil-like compound, 2% ceramide, 0.5% emulsifier, 0.3% stabilizer, 30% organic solvent, and water as the balance.

[0147] The hydrophilic modified starch is 2-methacryloyloxyethyl phosphorylcholine (MPC) modified starch Amylose-g-MPC.

[0148] The starch is amylose; the number-average molecular weight of the starch is 55418.

[0149] The structure of the hydrophilic modified starch is as follows:

[0150]

[0151] The 2-methacryloyloxyethylphosphorylcholine is grafted onto the glucose molecule-[6]-hydroxyl group of starch; the theoretical grafting rate is 231 / 308 = 75%; the molecular weight of the Amylose-g-MPC is 141797.

[0152] The minoxidil-like compound is composed of pyrrolidine diaminopyrimidine oxide and diaminopyrimidine oxide; the mass ratio of the pyrrolidine diaminopyrimidine oxide and diaminopyrimidine oxide is 1:3.

[0153] The ceramide is ceramide E.

[0154] The emulsifier is cocoyl glucoside; the stabilizer is cholesterol; and the organic solvent is octyldodecyl alcohol.

[0155] The preparation method of the hair loss prevention nanocomposition includes the following steps:

[0156] By weight percentage, 1% modified starch Amylose-g-MPC, 1% pyrrolidine diaminopyrimidine oxide, 3% diaminopyrimidine oxide, 2% ceramide E, 0.5% cocoyl glucoside, and 0.3% cholesterol were dissolved in 30% octyldodecyl alcohol. The solution was heated to 80°C and stirred at 50 rpm for 60 min until the raw materials were uniformly mixed. After the raw materials were fully dissolved, the solution was cooled to room temperature to obtain the alcohol phase. The alcohol phase was added dropwise at a rate of 3 mL / min to a 62.2% aqueous solution. After the addition was complete, the solution was stirred at 500 rpm for 20 min. The solution was then dispersed by high-speed shearing (6000 rpm) for 20 min; followed by high-pressure microfluidic treatment at a homogenization pressure of 120 MPa for one homogenization cycle to prepare the anti-hair loss nanocomposition.

[0157] Example 26

[0158] An anti-hair loss nanocomposition according to an embodiment of the present invention comprises the following components by weight percentage:

[0159] The ingredients are: 1% hydrophilic modified starch, 4% minoxidil-like compound, 2% ceramide, 0.5% emulsifier, 0.3% stabilizer, 30% organic solvent, and water as the balance.

[0160] The hydrophilic modified starch is 2-methacryloyloxyethyl phosphorylcholine (MPC) modified starch Amylose-g-MPC.

[0161] The starch is amylose; the number-average molecular weight of the starch is 55418.

[0162] The structure of the hydrophilic modified starch is as follows:

[0163]

[0164] The 2-methacryloyloxyethylphosphorylcholine is grafted onto the glucose molecule-[6]-hydroxyl group of starch; the theoretical grafting rate is 231 / 308 = 75%; the molecular weight of the Amylose-g-MPC is 141797.

[0165] The minoxidil-like compound is composed of pyrrolidine diaminopyrimidine oxide and diaminopyrimidine oxide; the mass ratio of the pyrrolidine diaminopyrimidine oxide and diaminopyrimidine oxide is 1:3.

[0166] The ceramide is ceramide E.

[0167] The emulsifier is polyglycerol-10 laurate; the stabilizer is sodium cholate; and the organic solvent is dipropylene glycol.

[0168] The preparation method of the hair loss prevention nanocomposition includes the following steps:

[0169] By weight percentage, 1% modified starch Amylose-g-MPC, 1% pyrrolidine diaminopyrimidine oxide, 3% diaminopyrimidine oxide, 2% ceramide E, 0.5% polyglycerol-10 laurate, and 0.3% sodium cholate were dissolved in 30% dipropylene glycol. The solution was heated to 40°C and stirred at 500 rpm for 20 min until the raw materials were uniformly mixed. After the raw materials were fully dissolved, the solution was cooled to room temperature to obtain the alcohol phase. The alcohol phase was added dropwise to a 62.2% aqueous solution at a rate of 1 mL / min. After the addition was complete, the solution was stirred at 200 rpm for 30 min. The solution was then dispersed by high-speed shearing (12000 rpm) for 15 min; followed by high-pressure microfluidic treatment at a homogenization pressure of 50 MPa for 8 homogenization cycles to prepare the anti-hair loss nanocomposition.

[0170] Comparative Example 1

[0171] The present invention provides a comparative example of an anti-hair loss nanocomposition, which differs from Example 1 in that it uses the surfactant Tween-20 for solubilization.

[0172] The preparation method of the hair loss prevention nanocomposition includes the following steps:

[0173] By weight percentage, 1.5% of pyrrolidine diaminopyrimidine oxide and 4.5% of diaminopyrimidine oxide were dissolved in 30% Tween-20, heated to 50°C, and stirred at 300 rpm for 30 min until the raw materials were uniformly mixed. After the raw materials were fully dissolved, the solution was cooled to room temperature to obtain phase A. The pH of deionized water was adjusted with citric acid to prepare an acidic solution with a pH of 5.00. Phase A solution was added dropwise to the 64% acidic solution at a rate of 5 mL / min. After the addition was completed, the solution was stirred at 400 rpm for 30 min. The solution was dispersed by high-speed shearing (11000 rpm) for 15 min, and then subjected to high-pressure microfluidic treatment at a homogenization pressure of 70 MPa for 4 homogenization cycles to prepare the anti-hair loss nanocomposition.

[0174] Comparative Example 2

[0175] The present invention provides a comparative example of an anti-hair loss nanocomposition, which differs from Example 1 in that it uses ethanol for solubilization.

[0176] The preparation method of the hair loss prevention nanocomposition includes the following steps:

[0177] By weight percentage, 1.5% of pyrrolidine diaminopyrimidine oxide and 4.5% of diaminopyrimidine oxide were dissolved in 30% anhydrous ethanol. The solution was heated to 50°C and stirred at 300 rpm for 30 min until the raw materials were uniformly mixed. After the raw materials were fully dissolved, the solution was cooled to room temperature to obtain phase A solution. The pH of deionized water was adjusted with citric acid to prepare an acidic solution with a pH of 5.00. Phase A solution was added dropwise to the 64% acidic solution at a rate of 5 mL / min. After the addition was completed, the solution was stirred at 400 rpm for 30 min. The solution was dispersed by high-speed shearing (11000 rpm) for 15 min; then subjected to high-pressure microfluidic treatment at a homogenization pressure of 70 MPa for 4 homogenization cycles to prepare the anti-hair loss nanocomposition.

[0178] Comparative Example 3

[0179] The present invention provides a comparative example of an anti-hair loss nanocomposition, which differs from Example 1 in that the 62% by weight of the acidic solution with pH 5.00 in Example 1 is replaced with a 62% by weight of the acidic solution with pH 2.00, while the rest remains unchanged, to prepare the anti-hair loss nanocomposition.

[0180] Comparative Example 4

[0181] The present invention provides a comparative example of an anti-hair loss nanocomposition, which differs from Example 1 in that the 62% by weight of the acidic solution with pH 5.00 in Example 1 is replaced with 62% by weight of deionized water, while the rest remains unchanged, to prepare the anti-hair loss nanocomposition.

[0182] Comparative Example 5

[0183] The present invention provides a comparative example of an anti-hair loss nanocomposition, which differs from Example 1 in that the 62% by weight of the acidic solution with pH 5.00 in Example 1 is replaced with a 62% by weight of the alkaline solution with pH 8.00, while the rest remains unchanged, to prepare the anti-hair loss nanocomposition.

[0184] Comparative Example 6

[0185] The present invention provides a comparative example of an anti-hair loss nanocomposition, which differs from Example 1 in that: the modified starch Amylose-g-DEAEMA, which accounts for 1% by weight in Example 1, is replaced with modified starch Amylose-g-DEAEMA, which accounts for 0.1% by weight, while the rest remains unchanged, to prepare the anti-hair loss nanocomposition.

[0186] Comparative Example 7

[0187] The present invention provides a comparative example of an anti-hair loss nanocomposition, which differs from Example 1 in that: the modified starch Amylose-g-DEAEMA, which accounts for 1% by weight in Example 1, is replaced with modified starch Amylose-g-DEAEMA, which accounts for 3.0% by weight, while the rest remains unchanged, to prepare the anti-hair loss nanocomposition.

[0188] Comparative Example 8

[0189] The hair loss prevention nanocomposition of the comparative example of the present invention differs from that of Example 1 in that: 1.5% by weight of pyrrolidinyl diaminopyrimidine oxide and 4.5% by weight of diaminopyrimidine oxide are dissolved in 94% by weight of 1,3-propanediol to prepare an anti-hair loss alcoholic solution.

[0190] Comparative Example 9

[0191] The present invention provides a comparative example of an anti-hair loss nanocomposition, which differs from Example 17 in that the modified starch Amylose-g-MPC with a weight percentage of 1.0% in Example 17 is replaced with modified starch Amylose-g-MPC with a weight percentage of 0.1%, while the rest remains unchanged, to prepare the anti-hair loss nanocomposition.

[0192] Comparative Example 10

[0193] The present invention provides a comparative example of an anti-hair loss nanocomposition, which differs from Example 17 in that the modified starch Amylose-g-MPC with a weight percentage of 1.0% in Example 17 is replaced with modified starch Amylose-g-MPC with a weight percentage of 3.0%, while the rest remains unchanged, to prepare the anti-hair loss nanocomposition.

[0194] Comparative Example 11

[0195] The present invention provides a comparative example of an anti-hair loss nanocomposition, which differs from Example 17 in that the 2.0% by weight of ceramide E in Example 17 is replaced with 5.0% by weight of ceramide E, while the rest remains unchanged, to prepare the anti-hair loss nanocomposition.

[0196] Comparative Example 12

[0197] The present invention provides a comparative example of an anti-hair loss nanocomposition, which differs from Example 17 in that: 1% pyrrolidine diaminopyrimidine oxide and 3% diaminopyrimidine oxide in Example 17 are replaced with 4% minoxidil by weight, while the rest remain unchanged, to prepare the anti-hair loss nanocomposition.

[0198] Comparative Example 13

[0199] The comparative example of the present invention is a nano-composition for preventing hair loss, which differs from Example 17 in that: 1.0% of pyrrolidine diaminopyrimidine oxide, 3.0% of diaminopyrimidine oxide and 2.0% of ceramide E are dissolved in 94% 1,3-propanediol, heated to 50°C, and stirred at 300 rpm for 30 min until the above raw materials are mixed evenly to obtain an anti-hair loss alcohol solution.

[0200] Comparative Example 14

[0201] The hair loss prevention nanocomposition of the comparative example of the present invention differs from that of Example 17 in that it uses the surfactant Tween-20 for solubilization.

[0202] The preparation method of the hair loss prevention nanocomposition includes the following steps:

[0203] By weight percentage, 1.0% of pyrrolidine diaminopyrimidine oxide, 3.0% of diaminopyrimidine oxide, 2.0% of ceramide E, 0.5% of soybean lecithin, and 0.2% of cholesterol were dissolved in 30% Tween-20. The solution was heated to 50°C and stirred at 300 rpm for 30 min until the raw materials were uniformly mixed. After the raw materials were fully dissolved, the solution was cooled to room temperature to obtain phase A solution. Phase A solution was added dropwise to a 63.3% aqueous solution at a rate of 3 mL / min. After the addition was completed, the solution was stirred at 400 rpm for 30 min. The solution was dispersed by high-speed shearing (11000 rpm) for 15 min; then subjected to high-pressure microfluidic treatment at a homogenization pressure of 70 MPa for 4 homogenization cycles to prepare the anti-hair loss nanocomposition.

[0204] Comparative Example 15

[0205] The hair loss prevention nanocomposition of the comparative example of the present invention differs from that of Example 17 in that it uses ethanol for solubilization.

[0206] The preparation method of the hair loss prevention nanocomposition includes the following steps:

[0207] By weight percentage, 1.0% of pyrrolidine diaminopyrimidine oxide, 3.0% of diaminopyrimidine oxide, 2.0% of ceramide E, 0.5% of soybean lecithin, and 0.2% of cholesterol were dissolved in 30% anhydrous ethanol. The solution was heated to 50°C and stirred at 300 rpm for 30 min until the raw materials were uniformly mixed. After the raw materials were fully dissolved, the solution was cooled to room temperature to obtain the alcohol phase. The alcohol phase was added dropwise to a 63.3% aqueous solution at a rate of 3 mL / min. After the addition was complete, the solution was stirred at 400 rpm for 30 min. The solution was then dispersed by high-speed shearing (11000 rpm) for 15 min; followed by high-pressure microfluidic treatment at a homogenization pressure of 70 MPa for 4 homogenization cycles to prepare the anti-hair loss nanocomposition.

[0208] Comparative Example 16

[0209] The present invention provides a comparative example of an anti-hair loss nanocomposition, which differs from Example 17 in that: 0.5% soybean lecithin and 0.2% cholesterol in Example 17 are replaced with 0.7% deionized water by weight, while the rest remain unchanged, to prepare the anti-hair loss nanocomposition.

[0210] Experimental methods

[0211] (I) Particle size determination

[0212] The particle size and particle size distribution coefficient of the samples in Examples 1-26 and Comparative Examples 1-16 were characterized using a Malvern Nano-ZS90 dynamic light scattering particle size analyzer. The test angle was 90° and the test temperature was 25°C. Each group of experiments was conducted in triplicate, and the arithmetic mean of the experimental results was taken.

[0213] (II) Encapsulation efficiency determination

[0214] The encapsulation rate of the anti-hair loss active ingredient (generally, the content of diaminopyrimidine oxide is measured; in Example 5, the content of pyrrolidinyl diaminopyrimidine oxide is measured) in the samples of Examples 1-26 and Comparative Examples 1-16 was determined: 200 μL of the anti-hair loss nanocomposition was taken, and after ultrafiltration and centrifugation (9000 rpm, 30 min), 5 μL of the filtrate was taken and the content of the anti-hair loss active ingredient (pyrrolidinyl diaminopyrimidine oxide or diaminopyrimidine oxide) in the filtrate was determined by high performance liquid chromatography (HPLC, Shimadzu, Japan). The content of the unencapsulated anti-hair loss active ingredient in the anti-hair loss nanocomposition was obtained. Take another sample of the above-mentioned anti-hair loss nanocomposition, add methanol, and ultrasonically demulsify at a ratio of sample:methanol = 1:9 (v / v) for 30 min. After filtration through a 0.45 μm organic filter membrane, take 5 μL of the sample solution and determine the content of the anti-hair loss active ingredient (pyrrolidinyl diaminopyrimidine oxide or diaminopyrimidine oxide) using a high-performance liquid chromatograph (HPLC, Shimadzu, Japan). The total content of the anti-hair loss active ingredient in the anti-hair loss nanocomposition is then obtained. The encapsulation efficiency (EE) of the anti-hair loss active ingredient (pyrrolidinyl diaminopyrimidine oxide or diaminopyrimidine oxide) in the anti-hair loss nanocomposition is calculated according to formula (1). The analytical column used in the HPLC system is a non-polar C18 column, the mobile phase is acetonitrile, the flow rate is 1.0 mL / min, and the column temperature is 30℃. Each group of experiments is performed in triplicate, and the arithmetic mean of the experimental results is taken.

[0215]

[0216] Wherein, C1 represents the concentration of the unencapsulated anti-hair loss active ingredient (pyrrolidinyl diaminopyrimidine oxide or diaminopyrimidine oxide) in the sample; C0 represents the total concentration of the anti-hair loss active ingredient (pyrrolidinyl diaminopyrimidine oxide or diaminopyrimidine oxide) in the sample after methanol demulsification.

[0217] Table 1. Particle size and encapsulation efficiency results of samples from Examples 1-16 and Comparative Examples 1-7.

[0218]

[0219]

[0220]

[0221] The particle size characterization and encapsulation efficiency test results of Examples 1-16 and Comparative Examples 1-7 are shown in Table 1.

[0222] Comparative examples 1, 2-4, and 3-5 show that the pH value of the anti-hair loss nanocomposite affects the particle size and encapsulation efficiency of the final product. As the pH value increases from 2.0 to 8.0, the particle size of the anti-hair loss nanocomposite first decreases and then increases; the encapsulation efficiency of the anti-hair loss active ingredient first increases and then decreases. When the pH value of the anti-hair loss nanocomposite is 2.0, 7.0, and 8.0, the encapsulation efficiency of the anti-hair loss active ingredient in the product is relatively low. Therefore, this invention selects a pH value of 3.0-6.0 for the anti-hair loss nanocomposite, preferably 5.0 (Example 1).

[0223] Comparing Examples 1 and 5-10, it is evident that maintaining a total weight percentage of 6% for the anti-hair loss active ingredient, the different ratios of pyrrolyl diaminopyrimidine oxide and diaminopyrimidine oxide affect the particle size and encapsulation efficiency of the final product. In the samples of Examples 1 and 5-10, the ratios of pyrrolyl diaminopyrimidine oxide and diaminopyrimidine oxide were 1.5:4.5, 6:0, 3:3, 2:4, 1.2:4.8, 1:5, and 0:6, respectively. The results indicate that, compared to encapsulating a single component, pyrrolyl diaminopyrimidine oxide (Example 5) or diaminopyrimidine oxide (Example 10), the modified starch-encapsulated samples (Examples 1 and 6-9) exhibited a higher encapsulation efficiency for the anti-hair loss active ingredient. Among them, when the ratio of pyrrolidine diaminopyrimidine oxide to diaminopyrimidine oxide was 1.5:4.5 (Example 1), the sample had the smallest particle size and the highest encapsulation rate of anti-hair loss active ingredient in the sample, which was 97.2%.

[0224] Comparative examples 1, 11-14, and 6-7 show that as the weight percentage of modified starch increases, the particle size of the samples first decreases and then increases, while the encapsulation of the anti-hair loss active ingredient first increases and then decreases. When the weight percentage of modified starch is 0.1% and 3%, the encapsulation rate of the anti-hair loss active ingredient is relatively low. Therefore, the present invention selects a weight percentage of modified starch of 0.2-2%, preferably 1% (Example 1).

[0225] Comparing Example 1, Comparative Example 1, and Comparative Example 2, it can be seen that compared with using surfactant (Tween-20) and ethanol to solubilize the anti-hair loss active ingredient, the modified starch used in this invention to encapsulate the anti-hair loss active ingredient results in a product with smaller particle size and a better encapsulation effect on the anti-hair loss active ingredient.

[0226] Table 2. Particle size and encapsulation efficiency results of samples from Examples 17-26 and Comparative Examples 9-12 and 14-16.

[0227]

[0228]

[0229] The particle size characterization and encapsulation efficiency test results of Examples 17-26 and Comparative Examples 9-12 and 14-16 are shown in Table 2.

[0230] When the active ingredient for preventing hair loss is a minoxidil-like compound and ceramides, as shown in Comparative Examples 17-20, the type of ceramide affects the particle size and encapsulation efficiency of the final product. In Examples 17-20, the types of ceramides were ceramide E, ceramide NH, ceramide AH, and ceramide NP, respectively. The results showed that the sample in Example 17 had the smallest particle size (102.9 nm) and the highest encapsulation efficiency (96.4%) of the active ingredient for preventing hair loss in Example 17.

[0231] Comparative Examples 17, 21-22, and 9 and 10 show that the amount of modified starch added affects the particle size and encapsulation efficiency of the final product. As the amount of modified starch added increases, the particle size of the samples first decreases and then increases, while the encapsulation efficiency first increases and then decreases. When the amount of modified starch added is 0.1% (Comparative Example 10) and 3% (Comparative Example 11), the encapsulation efficiency of the samples is relatively low. Therefore, the present invention selects a modified starch weight percentage of 0.2-2%, preferably 1% (Example 17).

[0232] Comparing Examples 17, 23, 24 and Comparative Example 11, it is evident that the amount of ceramide added affects the particle size and encapsulation efficiency of the final product. As the amount of ceramide added increases, the particle size of the samples first decreases and then increases, while the encapsulation efficiency first increases and then decreases. When the amount of ceramide added is 5% (Comparative Example 12), the encapsulation efficiency of the sample is relatively low. Therefore, this invention selects a ceramide weight percentage of 0.5-4%, preferably 2% (Example 17).

[0233] Comparing Example 17 and Comparative Example 12, it can be seen that the particle size and encapsulation efficiency of the compositions prepared by coating different active substances with modified starch are also very different. When modified starch is used to coat minoxidil, the resulting anti-shedding nanocomposition has a larger particle size and a lower encapsulation efficiency, indicating that the modified starch prepared in this invention is more suitable for coating pyrrolidinyl diaminopyrimidine oxide, diaminopyrimidine oxide, and ceramide.

[0234] Comparative Examples 17, 14, and 15 show that, compared with using surfactants Tween-20 (Comparative Example 14) and ethanol (Comparative Example 15) to solubilize the anti-hair loss active ingredients, the modified starch used in this invention to encapsulate the anti-hair loss active ingredients results in a product with smaller particle size and a better encapsulation effect on the anti-hair loss active ingredients.

[0235] Comparative Example 17 and Comparative Example 16 show that emulsifiers have a significant impact on the particle size and encapsulation efficiency of the anti-hair loss active ingredient in the composition. Without the addition of emulsifiers, the particle size of the anti-hair loss active ingredient will increase and the encapsulation efficiency will decrease.

[0236] (III) Transdermal absorption (penetration enhancement) test

[0237] The effects of Examples 1-4, Comparative Examples 1-5, and Comparative Example 8 on the transdermal absorption (penetration enhancement) ability of the anti-hair loss active ingredients (pyrrolidinyl diaminopyrimidine oxide and diaminopyrimidine oxide) were evaluated using a transdermal absorption (penetration enhancement) test. The specific methods are as follows:

[0238] In vitro transdermal experiments were conducted using a vertical diffusion cell with nude mouse skin as the model (abdominal skin, with subcutaneous fat and blood vessels removed). The receiving solution was PBS. The skin patch was fixed between the supply and receiving cells, with the skin layer facing downwards, and equilibrated for 20 minutes. Samples were collected and added to the supply cell, and the receiving solution was collected after 1 hour, 4 hours, 8 hours, and 24 hours. Methanol was added to the collected receiving solution, and the solution was ultrasonically treated for 30 minutes at a ratio of sample:methanol = 1:9 (v / v). After filtration through a 0.45 μm organic filter membrane, the contents of the anti-hair loss active ingredients (pyrrolidinyl diaminopyrimidine oxide and diaminopyrimidine oxide) were determined by high performance liquid chromatography (HPLC, Shimadzu, Japan), and the cumulative permeation per unit area was calculated accordingly. Each group of experiments was conducted in triplicate, and the arithmetic mean of the experimental results was taken. The formula for calculating the cumulative permeation per unit area on the skin patch is shown in formula (2):

[0239]

[0240] Among them, Q n The cumulative per unit area (μg / cm²) of the anti-hair loss active ingredients (pyrrolidinyl diaminopyrimidine oxide and diaminopyrimidine oxide) in the sample at time t. 2 ), A is the permeation area, C n C represents the concentration of the anti-hair loss active ingredients (pyrrolidinyl diaminopyrimidine oxide and diaminopyrimidine oxide) in the sample at time t. i The concentration of the anti-hair loss active ingredients (pyrrolidinyl diaminopyrimidine oxide and diaminopyrimidine oxide) in the sample before time t is the measured value, V is the total volume of the receiving liquid, and V0 is the sampling volume. Table 3 shows the permeability per unit area of ​​the anti-hair loss active ingredients (pyrrolidinyl diaminopyrimidine oxide and diaminopyrimidine oxide) in the samples of Examples 1-4, Comparative Examples 1-5, and Comparative Example 8.

[0241]

[0242]

[0243] The transdermal absorption characterization results of samples from Examples 1-4, Comparative Examples 1-5, and Comparative Example 8 are shown in Table 3. The cumulative permeation per unit area of ​​the anti-hair loss active ingredient in Example 1 at 1h, 4h, 8h, and 24h was significantly greater than that of the anti-hair loss alcohol solution in Comparative Example 8. As shown in Table 1, the particle size of the anti-hair loss nanocomposite has a significant impact on its transdermal absorption effect. The cumulative permeation per unit area of ​​the anti-hair loss active ingredient in Example 1 at 1h, 4h, 8h, and 24h was greater than that in Examples 2-4 and Comparative Examples 3-5, indicating that the pH value of the anti-hair loss nanocomposite affects the particle size of the final product, thus affecting the transdermal effect of the anti-hair loss active ingredient. In this invention, when the pH value of the anti-hair loss nanocomposite is 5.0, the particle size of the anti-hair loss nanocomposite is the smallest, and the final product has a better transdermal effect.

[0244] The cumulative permeation per unit area of ​​the anti-hair loss active ingredient in Example 1 at 1h, 4h, 8h and 24h was greater than that in Comparative Example 1 and Comparative Example 2, indicating that the product obtained by the present invention has a smaller particle size and better transdermal absorption effect than the samples solubilized with surfactant (Tween-20) or ethanol.

[0245] (iv) Skin irritation test

[0246] Test subjects: Samples from Examples 1 and 17 and Comparative Examples 1, 2, 8, and 13-15.

[0247] The specific method for multiple skin irritation tests in this invention is based on the standards in the "Cosmetic Safety Technical Specifications" (2015 edition), and the specific method is as follows:

[0248] Prepare 16 white rabbits that meet the experimental conditions, and use 4 white rabbits for each sample. Before the experiment, trim the fur on both sides of the spine on the back of the rabbits (the trimmed area is 3cm×3cm on each side).

[0249] Apply 0.5 mL of the sample to one side of the skin (applied area 2.5 cm × 2.5 cm), leaving the other side untreated as a control. Apply once daily for 14 consecutive days. Starting from the second day, trim the hair before each application. Remove any remaining sample with pure water. Observe the results after 1 hour.

[0250] According to the skin irritation / corrosion test table 4 of the "Cosmetic Safety Technical Specifications" (2015 edition), the control area and the test area were treated in the same way.

[0251] Results evaluation: The average score of each rabbit per day was calculated according to the following formula (3), and the skin irritation intensity of the rabbits was determined according to Table 5 of the Skin Irritation / Corrosion Test in the "Cosmetic Safety Technical Specifications" (2015 edition).

[0252] During the experiment, observe whether the skin has any symptoms other than skin irritation.

[0253]

[0254] Table 4 Skin Irritation Response Scoring

[0255]

[0256] Table 5 Skin Irritation Intensity Grading

[0257] integral mean strength 0-<0.5 Non-irritating 0.5-<2.0 Mild irritation 2.0-<6.0 moderately irritating 6.0–8.0 Strong irritant

[0258] Table 6. Skin irritation test results of samples from Examples 1, 17 and Comparative Examples 1, 2, 8, 13-15.

[0259]

[0260] The skin irritation test results of samples from Examples 1 and 17 and Comparative Examples 1, 2, 8, and 13-15 are shown in Table 6. The anti-hair loss nanocomposites of Examples 1 and 17 were non-irritating in the skin irritation test. The average skin irritation score of Comparative Example 1 was 1.93, indicating mild irritation; the average skin irritation score of Comparative Example 2 was 3.64, indicating moderate irritation; the average skin irritation score of Comparative Example 14 was 3.00, indicating moderate irritation; and the average skin irritation score of Comparative Example 15 was 3.43, indicating moderate irritation. This indicates that compared to using surfactants (Tween-20) or ethanol for solubilization, the present invention uses modified starch to encapsulate the anti-hair loss active ingredients, resulting in products with lower skin irritation. The average skin irritation score of Comparative Example 8 was 1.71, indicating mild irritation, while the average skin irritation score of Comparative Example 13 was 1.86, also indicating mild irritation. This suggests that compared to the anti-hair loss alcohol solution, encapsulating the anti-hair loss active ingredient with modified starch can reduce the skin irritation caused by the active ingredient.

[0261] (V) Test of the effect of inhibiting 5α reductase activity

[0262] Increased 5α-reductase activity is one of the main causes of androgenetic alopecia. Therefore, this invention evaluates the anti-hair loss efficacy of samples by testing their inhibitory effect on 5α-reductase activity. A blank control group, a positive control group (finasteride group), and a sample group were set up. The blank control group consisted of testosterone solution and 5α-reductase; the positive control group consisted of testosterone solution, 5α-reductase, and different concentrations of finasteride; and the sample group consisted of testosterone solution, 5α-reductase, and different concentrations of the sample (Examples 1, 17 and Comparative Examples 1, 2, 8, 13-15). Each group was brought to the same volume with PBS buffer and incubated at 37°C for 60 min. The reaction was terminated by adding ethyl acetate, shaking, centrifuging, and collecting the organic layer solution. The solution was evaporated to dryness, dissolved in methanol, and filtered through a 0.45 μm organic filter membrane. The testosterone content was determined using high-performance liquid chromatography (HPLC). The amount of testosterone (C) in the solution after the reaction was calculated based on the testosterone standard curve. The testosterone response (R) and the inhibition rate of 5α-reductase (I) were calculated according to formulas (4) and (5), respectively.

[0263] Testosterone response (R) = C 0min -C 60min (Formula 4)

[0264] Among them, C 0min C represents the amount of testosterone in the reaction system before the reaction. 60min This indicates the amount of testosterone in the reaction system after 60 minutes of reaction.

[0265]

[0266] Among them, R 空白 R represents the amount of testosterone reacted in the blank control group reaction system. 样品 This indicates the amount of testosterone reacted in the sample group reaction system.

[0267] Table 7. Inhibition results of finasteride, Examples 1, 17, and Comparative Examples 1, 2, 8, 13-15 on 5α-reductase activity.

[0268]

[0269]

[0270] Table 7 shows the inhibition results of finasteride, Examples 1 and 17, and Comparative Examples 1, 2, 8, and 13-15 on 5α-reductase activity. As can be seen from the table, at the test concentrations (1.0 mg / ml and 5.0 mg / ml), the testosterone response in Examples 1 and 17 was significantly reduced, and the inhibition rate of 5α-reductase was increased. Their inhibitory effect was similar to that of the positive control group (finasteride) (the amount of finasteride added was the same as the amount of hydrophobic active substance added in the examples), indicating that Examples 1 and 17 can effectively inhibit 5α-reductase activity. The inhibition rate of 5α-reductase activity in Example 1 was higher than that in Comparative Example 8 (anti-hair loss alcohol solution, i.e., tincture), and the inhibition rate of 5α-reductase activity in Example 17 was higher than that in Comparative Example 13 (anti-hair loss alcohol solution, i.e., tincture), indicating that encapsulating the anti-hair loss active ingredient with modified starch Amylose-g-DEAEMA can improve the inhibitory effect of the samples on 5α-reductase activity. The inhibition rate of 5α-reductase activity by the sample in Example 1 was higher than that of the samples in Comparative Examples 1 and 2, and the inhibition rate of 5α-reductase activity by the sample in Example 17 was higher than that of the samples in Comparative Examples 14 and 15. This indicates that encapsulating the anti-hair loss active ingredient with modified starch Amylose-g-DEAEMA has a better inhibitory effect on 5α-reductase activity than using surfactant (Tween-20) or anhydrous ethanol for solubilization.

[0271] (vi) Hair loss prevention effect test

[0272] According to the formulas in Table 8, minoxidil essence, essence of Example 1, essence of Comparative Example 1, essence of Comparative Example 2, and essence of Comparative Example 8 were prepared respectively, and human efficacy evaluation was conducted to test the effect of the anti-hair loss nanocomposition of the present invention on promoting hair growth. The subjects of the efficacy evaluation test were 150 people aged 20-50 years with total baldness or baldness, including 90 men and 60 women. The subjects were randomly divided into 5 groups of 30 people each, and used minoxidil essence, essence of Example 1, essence of Comparative Example 1, essence of Comparative Example 2, and essence of Comparative Example 8 respectively. The method of use was to take 2-3 mL of essence and apply it to the hair loss area twice a day, morning and evening, for three consecutive months. The efficacy evaluation criteria are as follows: (1) Significant effect: hair loss stops and black hair grows back in the hair loss area; (2) Effective: hair loss is significantly improved and black hair grows back in some hair loss areas; (3) Slight effect: hair loss is improved and vellus hair grows in the hair loss area; (4) Ineffective: hair loss is not improved or reduced and no new hair grows in the hair loss area.

[0273] Table 8. Formulation table (by weight) of Minoxidil serum, serum of Example 1, serum of Comparative Example 1, serum of Comparative Example 2, and serum of Comparative Example 8.

[0274]

[0275] Table 9 Results of the anti-hair loss efficacy of Minoxidil Essence, Example 1 Essence, Comparative Example 1 Essence, Comparative Example 2 Essence, and Comparative Example 8 Essence.

[0276] sample Effective (person) Valid (person) Minimal effect (person) Invalid (person) Significant efficiency (%) Minoxidil serum 16 10 4 0 53 Example 1: Essence 24 3 3 0 80 Comparative Example 1 Serum 9 12 5 4 30 Comparative Example 2 Serum 8 13 5 4 26 Comparative ratio 8 serum 13 10 6 1 43

[0277] Table 9 shows the human efficacy results of minoxidil serum, serum of Example 1, serum of Comparative Example 1, serum of Comparative Example 2, and serum of Comparative Example 8. The table shows that serum of Example 1 has a higher efficacy rate than serum of Comparative Example 8, indicating that encapsulating the anti-hair loss active ingredient with modified starch Amylose-g-DEAEMA results in a smaller particle size of the anti-hair loss nanocomposite, which is beneficial for the scalp absorption of the hydrophobic active ingredient, thus effectively improving the hair loss treatment effect. Furthermore, serum of Example 1 has a higher efficacy rate than serums of Comparative Examples 1 and 2, indicating that encapsulating the anti-hair loss active ingredient with modified starch Amylose-g-DEAEMA, compared to using surfactants (Tween-20) or anhydrous ethanol for solubilization, results in a smaller particle size and superior anti-hair loss effect in the prepared anti-hair loss nanocomposite.

[0278] (vii) Test of anti-hair loss and repair effects

[0279] According to the formulas in Table 10, minoxidil essence, essence of Example 17, essence of Comparative Example 9, and essence of Comparative Example 13-15 were prepared respectively. The essence matrix was used for human efficacy evaluation to test the anti-hair loss and scalp repair effects of the compositions of the present invention. The efficacy evaluation subjects were 180 healthy men or women aged 18-60 years with hair length between 5-40 cm, experiencing significant hair loss and mild thinning, and having a hair loss count greater than 10 strands after 60 combing tests. Among them, there were 108 men and 72 women. The subjects were randomly divided into 6 groups of 30 people each, and each group used minoxidil essence, essence of Example 17, or essence of Comparative Example 13-15 respectively. The method of use was to take 2-3 mL of essence and apply it to the hair loss area twice a day, morning and evening, for one month.

[0280] (1) Anti-hair loss effect test: Before and one month after use, volunteers' hair was combed by trained staff using the 60-comb method during interviews. The number of hairs lost was counted and recorded. The change rate of hair loss after one month of use was calculated to evaluate the anti-hair loss effect of the serum. A negative change rate of hair loss indicates that the volunteer's hair loss has decreased, and the larger the negative value, the better the anti-hair loss effect.

[0281] (2) Repair effect test: The transepidermal water loss of the scalp was detected by the Tewameter TM330T three-probe skin moisture loss test probe. Each area was measured once, and each test lasted 30 seconds. The average value of the last 20 seconds was taken as the measured value. The change rate of transepidermal water loss of the scalp was calculated to evaluate the repair effect of the essence. A negative change rate of transepidermal water loss of the scalp indicates that the transepidermal water loss of the scalp has decreased and the scalp barrier has improved. The larger the negative value, the better the scalp repair effect.

[0282] The average value, difference, and rate of change were calculated based on the number of hairs lost and the measurement of transcutaneous scalp moisture loss. The average value results are shown in Table 10. The formulas for calculating the average value, difference, and rate of change are as follows:

[0283]

[0284] Where, x n This represents the individual parameter detection value, and n represents the number of valid data.

[0285]

[0286] Among them, X Tn X represents the average value of the parameters detected at the nth time point after use. T0 This represents the average value of the parameters detected before use.

[0287]

[0288] Among them, X T0 This represents the average value of the parameters detected before use, and the rate of change represents the degree of change of the mean relative to the initial value.

[0289] Table 10 Formulation of Minoxidil Serum, Example 17 Serum, and Comparative Examples 13-15 Serum

[0290]

[0291] Table 11 Results of transdermal water loss tests for minoxidil serum, serum of Example 17, and serums of Comparative Examples 13-15

[0292]

[0293]

[0294] Table 11 shows the transepidermal water loss test results for minoxidil essence, essence of Example 17, and comparative examples 13-15. As can be seen from the table, the blank control group (base essence) had no scalp repair effect. After three months of use of minoxidil essence, essence of Example 17, essence of Comparative Example 14, and essence of Comparative Example 15, the changes in transepidermal water loss of the subjects' scalps were -4.9% (minoxidil essence), -19.0% (essence of Example 17), -3.4% (essence of Comparative Example 13, anti-hair loss repair active ingredient alcohol solution, equivalent to tincture), -11.6% (essence of Comparative Example 14, anti-hair loss nanocomposite prepared by surfactant solubilization), and -12.4% (essence of Comparative Example 15, anti-hair loss nanocomposite prepared by ethanol solubilization), respectively. The use of small-particle-size anti-hair loss nanocomposite in the essence of Example 17 is beneficial for the transdermal absorption of active substances. Therefore, the essence of Example 17 has the best repair effect on the scalp. Comparative Example 13 only uses ethanol to dissolve hydrophobic active substances. However, the addition of a large amount of ethanol is not conducive to the repair of the scalp barrier. Comparative Examples 13 and 14 respectively use surfactant solubilization and ethanol solubilization to prepare anti-hair loss nanocomposite. However, compared with the anti-hair loss nanocomposite prepared with modified starch, the anti-hair loss nanocomposite of Comparative Examples 13 and 14 has a larger particle size, which is not conducive to the transdermal absorption of ceramide. Therefore, the repair effect of Comparative Examples 13 and 14 is poor.

[0295] Table 12 Results of the anti-hair loss efficacy of minoxidil serum, serum from Example 17, and serums from Comparative Examples 13-15

[0296] sample Change rate of hair loss Minoxidil serum -25.3％ Example 17 Essence -27.1％ Comparative ratio 13 serum -14.6％ Comparative Example 14 Serum -12.0％ Comparative ratio 15 serum -5.2％ Matrix essence 0.2％

[0297] Table 12 shows the results of the anti-hair loss efficacy of minoxidil essence, essence of Example 17, and essences of Comparative Examples 13-15. The table shows that essence of Example 17 has a better hair loss prevention effect than essence of Comparative Example 13, indicating that compared with tinctures, the essence prepared by encapsulating minoxidil-like compounds with modified starch has a better anti-hair loss effect. Essence of Example 17 has a better anti-hair loss effect than essences of Comparative Examples 14 and 15, indicating that encapsulating the active ingredients with modified starch, compared with using the surfactant Tween-20 and anhydrous ethanol for solubilization, results in a smaller particle size of the anti-hair loss nanocomposite, better transdermal absorption of the active substances, and a superior anti-hair loss effect in the final product.

[0298] Finally, it should be noted that the above embodiments are only used to illustrate the technical solutions of the present invention and are not intended to limit the scope of protection of the present invention. Although the present invention has been described in detail with reference to preferred embodiments, those skilled in the art should understand that modifications or equivalent substitutions can be made to the technical solutions of the present invention without departing from the essence and scope of the technical solutions of the present invention.

Claims

1. A nano-composition for preventing hair loss, characterized in that, It comprises the following components by weight percentage: 0.2-2% hydrophilic modified starch, 1-14% hydrophobic active ingredient for preventing hair loss, 0.1-10% emulsifier, 0.1-10% stabilizer, 20-50% organic solvent, and 10-78.1% water; wherein the hydrophobic active ingredient for preventing hair loss includes minoxidil-like compounds; The hydrophilic modified starch is diethylaminoethyl methacrylate modified starch or 2-methacryloyloxyethylphosphorylcholine modified starch. The structure of the hydrophilic modified starch is as follows: ， ； The number-average molecular weight of the starch is 50,000-70,000; The diethylaminoethyl methacrylate or 2-methacryloyloxyethylphosphonic choline is grafted onto the glucose molecule-[6]-hydroxyl group of starch; The minoxidil-like compounds include at least one of pyrrolidinyl diaminopyrimidine oxide and diaminopyrimidine oxide; The emulsifier includes at least one of soybean lecithin, hydrogenated soybean lecithin, dipalmitoylphosphatidylcholine, egg yolk lecithin, PEG-40 hydrogenated castor oil, PEG-60 hydrogenated castor oil, cocoyl glucoside, and polyglycerol-10 laurate; the stabilizer includes at least one of cholesterol, phytosterols, glyceryl monooleate, and sodium cholate; the organic solvent includes at least one of 1,3-propanediol, glycerol, 1,4-butanediol, pentanediol, 1,2-hexanediol, dipropylene glycol, diethylene glycol, octyl dodecanol, octyl / decyl triglyceride, dichloromethane, acetone, tetrahydrofuran, and dimethyl sulfoxide.

2. The anti-hair loss nanocomposition as described in claim 1, characterized in that, The starch is amylose.

3. The anti-hair loss nanocomposition as described in claim 1, characterized in that, The mass ratio of the pyrrolidinyl diaminopyrimidine oxide to the diaminopyrimidine oxide is 1:(1~5).

4. The anti-hair loss nanocomposition as described in claim 1, characterized in that, The hydrophobic active ingredient for preventing hair loss also includes ceramide, which is present in the anti-hair loss nanocomposition at a weight percentage of 0.5-4%.

5. The anti-hair loss nanocomposition as described in claim 4, characterized in that, The ceramide is at least one of ceramide E, ceramide EOH, ceramide EOP, ceramide AP, ceramide AS, ceramide AH, ceramide NP, ceramide ND, and ceramide NH.

6. The method for preparing the anti-hair loss nanocomposition according to any one of claims 1 to 5, characterized in that, Includes the following steps: (1) Dissolve the hydrophilic modified starch, anti-hair loss hydrophobic active ingredient, emulsifier and stabilizer in an organic solvent, heat and stir to dissolve, and obtain phase A solution; (2) When the hydrophilic modified starch is diethylaminoethyl methacrylate modified starch, the anti-hair loss hydrophobic active ingredient is a minoxidil-like compound. The A phase solution is added dropwise to an acidic solution. After the addition is complete, stirring is continued to obtain a mixed solution. When the hydrophilic modified starch is 2-methacryloyloxyethyl phosphorylcholine modified starch, the anti-hair loss hydrophobic active ingredient is a minoxidil-like compound and a ceramide. The A phase solution is added dropwise to water. After the addition is complete, stirring is continued to obtain a mixed solution. (3) The mixed solution is subjected to nano-processing to obtain a hair loss prevention nano-composition.

7. The preparation method according to claim 6, characterized in that, Satisfy at least one of the following (a) to (d): (a) The acidic solution is obtained by dissolving a pH adjuster in water; the pH adjuster accounts for 5-15% by weight of the acidic solution; (b) The pH of the acidic solution is 3-6; (c) The nano-sizing process includes shear dispersion treatment and microfluidic homogenization treatment; (d) The shearing and dispersion treatment is performed by shearing at 8000-12000 rpm for 10-60 min; the homogenization pressure of the microjet homogenization treatment is 50-120 MPa, and the number of homogenization cycles is 1-8.

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