CN110917062A

CN110917062A - Nano emulsion for promoting hair growth and preparation method thereof

Info

Publication number: CN110917062A
Application number: CN201911315867.5A
Authority: CN
Inventors: 赵锴
Original assignee: Guangzhou Han Jinliang Cosmetics Co Ltd
Current assignee: Guangzhou Han Jinliang Cosmetics Co Ltd
Priority date: 2019-12-18
Filing date: 2019-12-18
Publication date: 2020-03-27

Abstract

The invention discloses a nano emulsion for promoting hair growth and a preparation method thereof, wherein the nano emulsion comprises a hair growth promoting compound consisting of pyrrolidinyl diaminopyrimidine oxide and baicalin, and a nano compound consisting of polyoxyethylene castor oil, lecithin, ethyl oleate, glutathione and ethanol and having a particle size of 10-133 m; the mass ratio of the pyrrolidinyl diaminopyrimidine oxide to the baicalin is 5: 2. The nanometer compound for promoting hair growth provided by the invention is an effective hair growth substance composed of pyrrolidinyl diaminopyrimidine oxide and baicalin, can effectively promote hair growth, and is low in irritation, good in stability and stronger in effect after being prepared into nanometer emulsion; the preparation method is simple in preparation process, can prepare the nano-composite with the hair growth effect at low temperature and normal pressure, does not contain any toxic reagent, is green and efficient, has a short period and high yield, and is easy to popularize and produce on a large scale.

Description

Nano emulsion for promoting hair growth and preparation method thereof

Technical Field

The invention belongs to the technical field of cosmetic preparation, relates to a compound for promoting hair growth, and particularly relates to a nanoemulsion for promoting hair growth and a preparation method thereof.

Background

The alopecia is mainly androgenetic alopecia which accounts for about 86% of the alopecia population, is mainly caused by genetic factors and is also related to combined effects of 5 α -reductase with overhigh activity, increased expression of male hormone receptors, blood circulation obstruction around hair follicles, bacterial infection, skin inflammation and the like at present, the alopecia can be caused at any age, currently, available treatment methods for the alopecia are extremely limited, western medicines mainly comprise chemical compositions represented by minoxidil, finasteride, JAK inhibitors and the like, but the western medicines are not suitable for the alopecia population due to narrow adaptation diseases, obvious side effects and high price, the traditional Chinese medicines have small toxic and side effects, low price and great advantages and can be easily obtained, the traditional Chinese medicines are often used for the alopecia population due to poor content and stability of extracts of traditional Chinese medicines produced by taking plant extracts as raw materials, the effective components of the hair growing substances and the high stability of the traditional Chinese medicines are not easy to be used, the effective tincture is not easy to obtain great significance, and the effective tincture is not easy to ensure.

Therefore, the development of a product capable of treating androgenic alopecia is imminent.

Disclosure of Invention

The present invention aims to overcome the defects of the prior art and provide a nano emulsion for promoting hair growth and a preparation method thereof. The nanoemulsion provided by the invention can effectively break through the stratum corneum of the skin, and penetrate into hair follicles, so that the active substance components are absorbed through the skin, and the hair growth is effectively promoted.

In order to achieve the purpose, the invention adopts the technical scheme that: a compound for promoting hair growth comprises pyrrolidinyl diaminopyrimidine oxide and baicalin; the mass ratio of the pyrrolidinyl diaminopyrimidine oxide to the baicalin is 5: 2.

The pyrrolidinyl diaminopyrimidine oxide is a hair growth promoter, is similar to minoxidil in structure, has different action principles, does not belong to the class of medicines, is a raw material approved by cosmetics, is safe and free of toxic and side effects, influences potassium ion channels through antagonism to a potassium ion channel switch inhibitor, promotes proliferation of epidermal hair papilla cells, relaxes blood vessels around hair follicles, improves scalp microcirculation, provides nutrition necessary for hair growth, promotes conversion of hair from a resting period to a growing period, and maintains a longer growing period.

Baicalin is an androgen receptor antagonist, has the effects of promoting the induction of the hair growth phase and increasing the activity of hair follicle dermal papilla cells, stimulating the secretion of vascular endothelial growth factors by the hair follicle dermal papilla cells to promote the growth of hair follicles, and activating a classical Wnt/β -catenin signaling pathway to increase the proliferation and differentiation capacities of fibroblasts and osteoblasts.

The invention preferably selects the combination of the pyrrolidinyl diaminopyrimidine oxide and the baicalin, and the mass ratio of the pyrrolidinyl diaminopyrimidine oxide to the baicalin is 5:2, so that the composition has the effect of synergistically promoting hair growth.

The complexes are useful for preparing products for promoting hair growth.

Also claimed is a hair growth lotion comprising the hair growth promoting complex.

Preferably, the hair growth promoting emulsion is a hair growth promoting nanoemulsion comprising the hair growth promoting compound and a nanocomposite.

In a preferred embodiment of the present invention, the content of the hair growth promoting composition in the nanoemulsion is 7% by mass.

As a preferred embodiment of the invention, the nano-composite consists of lecithin, polyoxyethylene castor oil, ethyl oleate, glutathione and ethanol, and the particle size of the nano-composite is 10-133 nm.

The lecithin, the polyoxyethylene castor oil, the ethyl oleate, the glutathione and the ethanol form a nano compound with water, namely a thermodynamically stable dispersion system formed by mixing a surfactant, an auxiliary surfactant, oil and water in a proper proportion. It has the incomparable characteristics of other drug carriers: 1) the appearance is transparent or semitransparent, the particles are uniform and the particle size is small; 2) the system is thermodynamically stable; 3) the preparation is simple, can be formed by only needing proper proportion of each component without much external force acting, and is independent of the adding sequence of the oil-water phase; 4) can be uniformly mixed with oil phase and water phase within a certain range; 5) increasing the solubility of poorly soluble drugs; 6) protecting easily oxidized and unstable medicaments; 7) reduce the toxicity of certain drugs; 8) the nano-emulsion has good drug dispersibility, rapid absorption, improved drug bioavailability and low viscosity; 9) the transdermal diffusion rate of the medicine can be obviously increased when the transdermal drug delivery system is used.

On the basis of the prepared nano composite, a novel hair growth promoter and an androgen receptor antagonist are sequentially added to form the composite for promoting hair growth, the small-size effect of nano particles in a nano emulsion system is utilized, active ingredients can be carried, the composite can rapidly permeate into the deep scalp layer and hair follicles, the hair follicles are activated, metabolism is promoted, the synergistic effect of the medicine and the nano emulsion is fully exerted, the effects of hair growth and hair growth are achieved, the hair loss symptom is fundamentally improved, and the healthy growth of the hair is promoted.

As a preferred embodiment of the present invention, in the nanocomposite, the mass ratio of the polyoxyethylene castor oil, lecithin, ethyl oleate, glutathione and ethanol is 15: 5: 20: 1: 10.

the invention optimizes the components of the prepared nano-composite, prepares the nano-composite according to the proportion, and obtains the composite with the particle size of about 68nm and the best stability.

Further, the nanoemulsion also comprises an auxiliary material.

As a preferable embodiment of the invention, the auxiliary material comprises a preservative accounting for 0.01-1% of the nano-emulsion by mass and/or an aromatizer accounting for 0.3-0.5% of the emulsion by mass.

As a preferred embodiment of the invention, the preservative is one or more of glyceryl caprylate, paraben, p-hydroxyacetophenone, caprylyl hydroximic acid and phenoxyethanol, and the preservative accounts for 0.1 percent of the mass of the nano emulsion; the flavoring agent is essence and accounts for 0.3% of the weight of the nano emulsion.

As a preferred embodiment of the present invention, the nano emulsion comprises the following components by mass percent: 2-10% of lecithin, 1-20% of polyoxyethylene castor oil, 5-25% of ethyl oleate, 1-5% of glutathione, 2-10% of ethanol, 5% of pyrrolidinyl diaminopyrimidine oxide, 2% of baicalin, 0.1% of phenoxyethanol, 0.3% of essence and the balance of deionized water.

The invention also provides a preparation method of the nano emulsion, which comprises the following steps:

(1) stirring polyoxyethylene castor oil, lecithin, ethyl oleate and ethanol glutathione at normal temperature, adding the balance of deionized water, uniformly mixing, and stirring to obtain a transparent and uniform nano composite;

(2) adding pyrrolidinyl diaminopyrimidine oxide and baicalin into the nano-composite in the step (1), and uniformly stirring at room temperature;

(3) and (3) adding auxiliary materials into the mixture obtained in the step (2), and uniformly stirring.

As a preferred embodiment of the invention, the stirring speed in the step (1) is 200r/min, and after adding the deionized water, the stirring is continued for 3 hours.

The invention provides a compound for promoting hair growth, which is formed by pyrrolidinyl diaminopyrimidine oxide and baicalin in a certain proportion, the pyrrolidinyl diaminopyrimidine oxide and the baicalin have a synergistic effect, and can remarkably promote hair growth and more comprehensively prevent and treat alopecia; the compound for promoting hair growth and the nano compound are prepared into corresponding nano emulsion, and a nano compound system in the nano emulsion is optimized, so that the obtained nano compound has small particle size and better stability, and can effectively assist hair growth substances to penetrate through cuticles and enter hair follicles to promote hair growth. Compared with the traditional hair restorer, the nano emulsion prepared by the invention has the advantages of safe components and no stimulation; can effectively promote hair growth and solve the problem of hair loss. The invention also provides a preparation method of the nano-composite for promoting hair growth, which has simple preparation process, can prepare the nano-composite with the hair growth effect at low temperature and normal pressure, does not adopt any toxic reagent, is green and efficient, has short period and high yield, and is easy to popularize and produce on a large scale.

Drawings

Fig. 1 shows the results of hair follicle counting by Image J software for each group of mice.

Detailed Description

To better illustrate the objects, aspects and advantages of the present invention, the present invention will be further described with reference to the accompanying drawings and specific embodiments.

Example 1

Adding 15% polyoxyethylene castor oil, 5% lecithin, 20% ethyl oleate, 10% ethanol and 1% glutathione at normal temperature and 200r/min under stirring, adding the rest of deionized water, uniformly mixing, stirring for 3h to form a transparent and uniform nano-composite, adding 5% pyrrolidinyl diaminopyrimidine oxide and 2% baicalin, stirring at room temperature, and finally adding 0.1% phenoxyethanol and 0.3% essence.

Example 2

Adding 15% of polyoxyethylene castor oil, 4% of lecithin, 25% of ethyl oleate, 2% of ethanol and 3% of glutathione into the rest of deionized water at the normal temperature and the rotation speed of 200r/min under stirring, uniformly mixing, stirring for 3h to form a transparent and uniform nano compound, adding 5% of pyrrolidinyl diaminopyrimidine oxide and 2% of baicalin, stirring at the room temperature, and finally adding 0.1% of phenoxyethanol and 0.3% of essence.

Example 3

Adding 15% polyoxyethylene castor oil, 2% lecithin, 20% ethyl oleate, 10% ethanol and 2% glutathione at normal temperature and 200r/min under stirring, adding the rest of deionized water, uniformly mixing, stirring for 3h to form a transparent and uniform nano-composite, adding 5% pyrrolidinyl diaminopyrimidine oxide and 2% baicalin, stirring at room temperature, and finally adding 0.1% phenoxyethanol and 0.3% essence.

Example 4

Adding 15% polyoxyethylene castor oil, 10% lecithin, 15% ethyl oleate, 8% ethanol and 1% glutathione into the rest of deionized water at the normal temperature of 200r/min under stirring, uniformly mixing, stirring for 3h to form a transparent and uniform nano-composite, adding 5% pyrrolidinyl diaminopyrimidine oxide and 2% baicalin, stirring at the room temperature, and finally adding 0.1% phenoxyethanol and 0.3% essence.

Example 5

Adding 20% polyoxyethylene castor oil, 6% lecithin, 10% ethyl oleate, 10% ethanol and 1% glutathione at normal temperature and 200r/min under stirring, adding the rest of deionized water, uniformly mixing, stirring for 3h to form a transparent and uniform nano-composite, adding 5% pyrrolidinyl diaminopyrimidine oxide and 2% baicalin, stirring at room temperature, and finally adding 0.1% phenoxyethanol and 0.3% essence.

Control group 1

Adding 15% polyoxyethylene castor oil, 5% lecithin, 20% ethyl oleate, 10% ethanol and 1% glutathione at normal temperature and a rotation speed of 200r/min, stirring, adding the rest of deionized water, uniformly mixing, stirring for 3h to form a transparent and uniform nano-composite, adding 3% minoxidil, stirring at room temperature, and finally adding 0.1% phenoxyethanol and 0.3% essence.

Control group 2

Adding 15% polyoxyethylene castor oil, 5% lecithin, 20% ethyl oleate, 10% ethanol and 1% glutathione at normal temperature and 200r/min under stirring, adding the rest of deionized water, uniformly mixing, stirring for 3h to form a transparent and uniform nano-composite, adding 5% pyrrolidinyl diaminopyrimidine oxide, stirring at room temperature, and finally adding 0.1% phenoxyethanol and 0.3% essence.

Control group 3

Adding 15% polyoxyethylene castor oil, 5% lecithin, 20% ethyl oleate, 10% ethanol and 1% glutathione at normal temperature and 200r/min under stirring, adding the rest of deionized water, mixing, stirring for 3 hr to obtain transparent and uniform nanometer compound, adding 2% baicalin, stirring at room temperature, and adding 0.1% phenoxyethanol and 0.3% essence.

Control group 4

Adding 15% polyoxyethylene castor oil, 5% lecithin, 20% ethyl oleate, 10% ethanol and 1% glutathione at normal temperature and 200r/min under stirring, adding the rest of deionized water, uniformly mixing, stirring for 3h to form a transparent and uniform nano-composite, adding 4% pyrrolidinyl diaminopyrimidine oxide and 3% baicalin, stirring at room temperature, and finally adding 0.1% phenoxyethanol and 0.3% essence.

Control group 5

Adding 15% polyoxyethylene castor oil, 5% lecithin, 20% ethyl oleate, 10% ethanol and 1% glutathione at normal temperature and 200r/min under stirring, adding the rest of deionized water, uniformly mixing, stirring for 3h to form a transparent and uniform nano-composite, adding 3% pyrrolidinyl diaminopyrimidine oxide and 1% baicalin, stirring at room temperature, and finally adding 0.1% phenoxyethanol and 0.3% essence.

Control group 6

Adding 15% of polyoxyethylene castor oil, 5% of lecithin, 20% of ethyl oleate, 10% of ethanol and 1% of glutathione into the rest of deionized water at the normal temperature and the rotation speed of 200r/min under stirring, uniformly mixing, stirring for 3h to form a transparent and uniform nano compound, adding 2% of pyrrolidinyl diaminopyrimidine oxide and 4% of baicalin, stirring at the room temperature, and finally adding 0.1% of phenoxyethanol and 0.3% of essence.

Blank group

Preparing nano emulsion: adding 15% polyoxyethylene castor oil, 5% lecithin, 20% ethyl oleate, 10% ethanol and 1% glutathione at normal temperature and 200r/min under stirring, adding the rest deionized water, mixing, stirring for 3 hr to obtain transparent and uniform nanometer compound, and adding 0.1% phenoxyethanol and 0.3% essence.

Optimized process for preparing nano emulsion

In order to screen out stable nano emulsion, the stable nano emulsion is obtained by optimizing the combination ratio according to 5-factor 5-level orthogonal experiment on different contents of polyoxyethylene castor oil, lecithin, ethyl oleate, glutathione and ethanol. The nanocomposite components in each test group were present in the mass percent of the total as shown in table 1.

The results are shown in table 1, when the mass fraction of the polyoxyethylene castor oil, lecithin, ethyl oleate, glutathione and ethanol is 15: 2: 20: 2: 10, the prepared nano composition has smaller grain diameter of 68nm, long stabilization time, meets the preparation requirements, and is finely adjusted on the basis that when the mass fractions of the polyoxyethylene castor oil, the lecithin, the ethyl oleate, the glutathione and the ethanol are 15: 5: 20: 1: at 10, the best effect is achieved in dissolving pyrrolidinyl diaminopyrimidine oxide and baicalin.

Table 1 five-factor five-level optimization test results

Second, safety test

The results of the skin irritation test of the hair growth promoting nanoemulsion of the present invention

Taking 35 healthy rabbits with weight of about 2kg, randomly dividing the rabbits into 7 groups, wherein each group comprises 5 rabbits, unhairing the two sides of the back skin of the rabbits 24h before the experiment, detecting whether the skin in the unhaired area is injured or not after the unhairing 24h, and applying the nano composition prepared in the examples 1-4, the control groups 1-3 and the blank groups for 3 times every day for 7 days, and observing the experiment results, wherein the experiment results are shown in table 2:

table 2 skin irritation test results

"+" indicates that the rabbit has red and swollen skin, inflammation and congestion;

"+ +" indicates that the rabbit has red and swollen skin, inflammation and congestion phenomena, and has increasing trend;

"-" indicates that the rabbit has no skin red swelling, inflammation and congestion;

as can be seen from the experimental results of table 2, the hair growth promoting nanoemulsion of the present invention has no irritation to the skin.

Second, stability test

And (3) performing centrifugal test, cold resistance test and heat resistance test on the 8 groups of nano emulsions, and primarily investigating the stability of the product.

The method comprises the following steps:

(1) and (3) centrifugal test: sampling 5g of a sample, placing the sample in a 10mL centrifugal test tube, adjusting the rotating speed to 3000r/min, centrifuging for 15min, taking out and observing;

(2) cold resistance test: weighing 10g of sample, placing the sample in a 50mL beaker, placing the beaker in a refrigerator at minus 8 ℃ for 24 hours, taking out the sample, and returning the sample to room temperature for observation;

(3) heat resistance test: 10g of the product was weighed, placed in a 50mL beaker, placed in a 55. + -. 2 ℃ desiccator for 6h and then observed.

The test results of each test are shown in Table 3.

Table 3 stability test results

From the results of table 3, it was confirmed that each sample passed the preliminary stability test without change in appearance compared to the sample before the test.

Thirdly, evaluation of the Effect of inhibiting 5 α -reductase Activity

According to related research, the 5 α -reductase catalyzes the participation of reduced coenzyme II (NADPH) required in the process of converting testosterone into dihydrotestosterone, the reduced NADPH has characteristic absorption at 340nm, the NADPH is converted into oxidized coenzyme II (NADP +) along with the reaction, the characteristic absorption at 340nm disappears, and the inhibitor effect of the 5 α -reductase can be detected according to the characteristic absorption change at 340nm of the NADPH in the reaction process.

The experimental method comprises the following steps:

(1) determination of blank control. To the reaction tube were added 2mL Buffer, 100. mu.L testosterone, 200. mu.L PBS Buffer (pH 7.2), 15. mu.L NADPH, and finally 15. mu.L enzyme, mixed and then measured for A340nm value, incubated at 37 ℃ and reacted for 10min and then measured for A340nm value. The DMSO blank reduction (. DELTA.A 0) was determined by subtracting the background of the NADPH blank reduction.

(2) And (4) measuring the inhibition effect of each group of reductase. To the reaction tube were added 2mL of Buffer (Buffer), 100. mu.L of testosterone, 200. mu.L of control group (1-4) and example group (1-4), 15. mu.L of NADPH, and finally 15. mu.L of enzyme, mixed and then measured for A340nm value, incubated at 37 ℃ and after reaction for 10min, measured for A340nm value. The reduction in reductase inhibition (. DELTA.an) was measured for each group by subtracting the background reduction in NADPH blank. The inhibition ratio of the enzyme was calculated as I (%) ═ Δ a 0- Δ An)/Δ a0 × 100%, and the experiment was repeated three times.

The results are shown in Table 4.

TABLE 4 results of experiments on inhibition of 5 α -reductase Activity

Group of	5 α -reductase inhibition (%)
		Blank group	-
Control group 1	71.6±1.5％
		Control group 2	58.4±1.1％
Control group 3	34.7±0.6％
		Control group 4	68.7±1.7％
Control group 5	63.5±2.1％
		Control group 6	58.0±0.8％
Example 1	72.6±1.3％

The experimental result in table 3 shows that the nano-composite can obviously reduce the conversion of testosterone to dihydrotestosterone, and the inhibiting effect of the compounded 5% pyrrolidinyl diaminopyrimidine oxide and 2% baicalin is improved to be close to that of the control group 1 compared with that of a single component, so that the prepared nano-composite has the activity of inhibiting 5 α -reductase.

Fourth, animal experiment

90 male mice are numbered according to weight, 10 mice are selected as blank groups according to a random number table method, and the rest mice are made into model groups. The blank group was injected with physiological saline, and the model-made mice were administered testosterone propionate subcutaneously to the back at a dose of 5mg/kg × d (0.1mg) for 6 weeks, to create an animal model of androgenetic alopecia. After the mice are successfully molded in the 6 th week of experiment, randomly dividing 80 mice of the molding group into a control group (1-4) and an example group (1-4), wherein each group comprises 10 mice, each group is externally smeared with a solution with a corresponding concentration, the external dose is 0.2ml according to the conversion of the volume of a human body/a mouse, the rest groups except a blank group are continuously injected with testosterone propionate to maintain the androgen level in the mouse, and the number of hair follicles is counted by applying Image J software to the same area of each group with the same size at the 12 th week. The results are shown in FIG. 1.

As can be seen from fig. 1, counting follicles by Image J software showed that the difference in the number of follicles was significant compared with the control group, experimental group and blank group; compared with a control group, the number of hair follicles of the experimental group is more than that of hair follicles of the control group, and the experimental result shows that the compounded pyrrolidinyl diaminopyrimidine oxide and baicalin are improved compared with that of one component used alone, and when the compounded effect of 5% of pyrrolidinyl diaminopyrimidine oxide and 2% of baicalin is the best.

Finally, it should be noted that the above embodiments are only used for illustrating the technical solutions of the present invention, and not for limiting the protection scope of the present invention, although the present invention is described in detail with reference to the preferred embodiments, it should be understood by those skilled in the art that modifications or equivalent substitutions can be made on the technical solutions of the present invention without departing from the spirit and scope of the technical solutions of the present invention.

Claims

1. A composition for promoting hair growth, comprising pyrrolidinyl diaminopyrimidine oxide and baicalin; the mass ratio of the pyrrolidinyl diaminopyrimidine oxide to the baicalin is 5: 2.

2. Use of a complex according to claim 1 for the preparation of a product for promoting hair growth.

3. A hair growth promoting emulsion comprising the hair growth promoting complex of claim 1 and an emulsion base.

4. The emulsion of claim 3, wherein the emulsion is a nanoemulsion and the emulsion matrix is a nanocomposite.

5. The emulsion of claim 4, wherein the nanocomposite comprises lecithin, polyoxyethylene castor oil, ethyl oleate, glutathione and ethanol, and the particle size of the nanocomposite is 10-133 nm.

6. The emulsion of claim 4, wherein the nanocomposite comprises a polyoxyethylene castor oil, lecithin, ethyl oleate, glutathione, and ethanol in a mass ratio of 15: 5: 20: 1: 10.

7. the emulsion of claim 4, further comprising an adjuvant.

8. The emulsion of claim 5, wherein the adjuvant comprises 0.01 to 1% by mass of the nanoemulsion of a preservative and/or 0.3 to 0.5% by mass of an odorant.

9. The emulsion according to claim 8, wherein the emulsion comprises the following components in percentage by mass: 5% lecithin, 15% polyoxyethylene castor oil, 20% ethyl oleate, 1% glutathione, 10% ethanol, 5% pyrrolidinyl diaminopyrimidine oxide, 2% baicalin, 0.1% phenoxyethanol, 0.3% essence and the balance of deionized water.

10. A process for the preparation of a nanoemulsion according to any of claims 4 to 9, characterised in that it comprises the following steps:

(1) stirring polyoxyethylene castor oil, lecithin, ethyl oleate and ethanol glutathione at a normal temperature and a rotating speed, adding the balance of deionized water, uniformly mixing, and stirring until a transparent and uniform nano-composite is formed;