CN117919248A - Injectable hair growth composition and preparation method and application thereof - Google Patents
Injectable hair growth composition and preparation method and application thereof Download PDFInfo
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- CN117919248A CN117919248A CN202410332444.9A CN202410332444A CN117919248A CN 117919248 A CN117919248 A CN 117919248A CN 202410332444 A CN202410332444 A CN 202410332444A CN 117919248 A CN117919248 A CN 117919248A
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- Prior art keywords
- minoxidil
- shell
- core
- injectable
- temperature
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Abstract
The invention relates to the technical field of medicines, and provides an injectable hair growth composition, a preparation method and application thereof, wherein the composition comprises the following components: core-shell microspheres, sodium hyaluronate and polydeoxyribonucleotide coated with minoxidil core layer by using shell layer; the preparation method comprises the following steps: dissolving a shell material in a solvent to form an oil phase solution; dissolving polyvinyl alcohol in water to obtain a polyvinyl alcohol aqueous solution; under the heating condition, adding a temperature-sensitive material and minoxidil into water, and cooling to form a temperature-sensitive inner core ball wrapping minoxidil liquid drops; adding the temperature-sensitive inner core spheres, the oil phase solution and the temperature-sensitive material which wrap minoxidil liquid drops into a polyvinyl alcohol water solution, heating after the solvent volatilizes, then cooling, and obtaining core-shell microspheres after treatment and freeze-drying; dissolving other substances in water to obtain a base solution; then dispersing the powder of the core-shell microspheres in a base solution to obtain the composition; it improves drug-carrying rate and slow-release effect and is easier to inject.
Description
Technical Field
The invention relates to the technical field of medicines, in particular to an injectable hair growth composition, and a preparation method and application thereof.
Background
With the continuous development of society, people's life work and rest and stress level have changed greatly, and the number of people suffering from alopecia has proliferated and tends to younger development. Androgenic alopecia (Androgenic alopecia, AGA), also known as seborrheic alopecia, is a chronic progressive disease, with 80% of patients suffering from alopecia exhibiting a degree of androgenic alopecia in 50% of women. The main causes of androgenic alopecia are: hair follicles are not receptive to the effects of androgens, genetic factors or hormonal changes, and psychological stress; lack of nutrition, such as lack of protein, sulfur-containing amino acids or vitamins, etc., aggravates alopecia in case of insufficient microcirculation; seborrhea. Furthermore, the onset of androgenic alopecia is not only related to androgens, but also has a clear relationship with changes in perifollicular inflammation, local bacterial proliferation in the scalp, and insufficient local nutrient supply.
The scalp provides good environment and sufficient nutrients for the growth and development of hair follicles, and according to the characteristics and clinical manifestations of scalp aging, theoretically, the thickness of the dermis layer can be increased by artificially supplementing or stimulating the growth of components of the dermis layer, such as collagen, so that the scalp is full and is close to a young state, a healthier growth environment can be provided for hair follicles in the dermis layer, and hair quality or alopecia can be improved.
Minoxidil is the most commonly used external medicine for treating alopecia at the present stage, the recommended dosage is 5% for men and 2% for women, and the growth of alopecia can be promoted by using a solution or foam preparation to smear scalp. However, the external minoxidil has a long period of taking the drug effect, usually needs to be used once to twice a day, and can be used for 6 months to see obvious effects, and the long-term external minoxidil can cause adverse reactions such as scalp itching, rash, desquamation and the like, and further damage to the scalp is caused instead, thereby aggravating the hair loss condition.
Therefore, how to make it exert better drug effect, reduce treatment period, and reduce side effects are important.
Disclosure of Invention
The invention aims to provide an injectable hair growth composition and a preparation method thereof, which improve the drug loading rate and the slow release effect, are easier to inject, shorten the treatment period and reduce the side effect.
The embodiment of the invention is realized by the following technical scheme:
An injectable hair growth composition comprising the following components: core-shell microsphere coated with minoxidil core layer, sodium hyaluronate, polydeoxyribonucleotide, amino acid and its derivative, vitamin and its derivative, trace element and bioactive molecule.
The preparation method comprises the following steps:
1) Dissolving a shell material in an organic solvent to form an oil phase solution;
2) Dissolving polyvinyl alcohol in the aqueous solution to obtain an aqueous solution of polyvinyl alcohol;
3) Under the heating condition, adding a temperature-sensitive material and minoxidil into an aqueous solution, stirring at a high speed to form liquid drops, and then cooling under the stirring condition to form a temperature-sensitive inner core ball wrapping the minoxidil liquid drops;
4) Adding the temperature-sensitive inner core spheres coated with minoxidil liquid drops and the oil phase solution obtained in the step 1) into the aqueous solution of the polyvinyl alcohol obtained in the step 2), stirring at the same time, adding a temperature-sensitive material to form an oil-in-water emulsion, continuously stirring, heating the solution after the organic solvent volatilizes, cooling to room temperature, and centrifuging, separating, washing, dispersing and freeze-drying to obtain core-shell microspheres coated with minoxidil core layers;
5) Dissolving sodium hyaluronate, polydeoxyribonucleotide, amino acid and its derivative, vitamin and its derivative, trace element and bioactive molecule in water to obtain base solution;
6) Dispersing the powder of the core-shell microsphere coated with the minoxidil core layer in the substrate solution prepared in the step 5) to obtain the injectable hair growth composition.
The invention also provides application of the injectable hair growth composition in preparing a medicament for treating alopecia.
The technical scheme of the embodiment of the invention has at least the following advantages and beneficial effects:
1. The injectable hair growth composition prepared by the invention uses shell materials such as polylactic acid and the temperature-sensitive material to be gathered on the surface of the temperature-sensitive inner core ball in a staggered way to form a shell; and then the temperature sensitive materials in the inner core ball and the outer shell flow out to form the drug-carrying microsphere with a core-shell structure, wherein minoxidil is used as a core layer, and shell materials such as polylactic acid are used as shell layers, so that the shell layers have loose and porous pores and become smaller in density, the drug-carrying rate and the slow release effect are greatly improved, and the drug-carrying microsphere is difficult to settle in a solution, is easy to uniformly disperse in a solution medium and is easier to inject.
2. The injectable hair growth composition has remarkable effect on hair growth, stimulates collagen production at scalp parts, provides healthier growth environment for hair follicles, can promote hair growth in a shorter time, avoids side effects caused by long-term external minoxidil, reduces the use frequency and dosage of medicines, avoids medicine loss caused by insufficient medicine absorption, and is easy to accept by patients and good in compliance.
Drawings
In order to more clearly illustrate the technical solutions of the embodiments of the present invention, the drawings that are needed in the embodiments will be briefly described below, it being understood that the following drawings only illustrate some embodiments of the present invention and therefore should not be considered as limiting the scope, and other related drawings may be obtained according to these drawings without inventive effort for a person skilled in the art.
FIG. 1 is a graph showing the results of drug release assays of example 3 of the present invention versus comparative example 1;
FIG. 2 is a graph showing comparison of growth of the dehairing sites of mice of each group according to the present invention;
FIG. 3 is a graph showing the integral comparison of the back hair growth of mice of each group according to the present invention;
Detailed Description
In order to make the objects, technical solutions and advantages of the embodiments of the present invention more clear, the technical solutions of the embodiments of the present invention will be clearly and completely described below. The specific conditions are not noted in the examples and are carried out according to conventional conditions or conditions recommended by the manufacturer. The reagents or apparatus used were conventional products commercially available without the manufacturer's attention.
The injectable hair growth composition and the preparation method thereof provided by the embodiment of the invention are specifically described below.
An injectable hair growth composition comprising the following components: core-shell microspheres, sodium hyaluronate and polydeoxyribonucleotide coated with minoxidil core layer by using shell layer; further comprises: amino acids and their derivatives, vitamins and their derivatives, trace elements, and bioactive molecules.
Further, the polydeoxyribonucleotide can be extracted from sperm of salmon, atlantic salmon, pacific salmon, silver salmon, and northern salmon.
Further, the shell layer of the core-shell microsphere comprises: one or more of polylactic acid, polyglycolide, polycaprolactone, polyethylene glycol-poly-l-lactic acid, polyethylene glycol-polyglycolide or polyethylene glycol-polycaprolactone (PEG-PCL).
Further, the mass ratio of the core-shell microsphere, the sodium hyaluronate, the polydeoxyribonucleotide, the amino acid and the derivative thereof, the vitamin and the derivative thereof, the trace elements and the bioactive molecules is as follows: 5-20%, 0.5-0.7%, 0.1-0.3%, 0-0.3%; the balance being water.
Further, the amino acids and derivatives thereof include, but are not limited to, the following components: arginine, ornithine, citrulline, acetylmethionine, acetylcysteine, lysine, methionine, tyrosine, cystine, cysteine, alpha-aminobutyric acid, alanine, asparagine, aspartic acid, glutamine, glutamic acid, glycine, histidine, hydroxyproline, isoleucine, leucine, phenylalanine, proline, serine, taurine, threonine, tryptophan, valine; the vitamins and their derivatives include, but are not limited to, the following components: one or more of vitamin C, vitamin B (vitamins B1, B2, B3, B5, B6, B8, B9, B12, panthenol, ethyl panthenol), vitamin H, and tocopheryl acetate; the microelements comprise, but are not limited to, one or more of zinc gluconate, zinc chloride, zinc sulfate, zinc carbonate and zinc pyrithione.
Further, the bioactive molecules include, but are not limited to: tripeptide-1 copper, biotin tripeptide-1, acetyltetrapeptide-3, sphinganine, pyrrolidinyl diaminopyrimidine oxide, myo-inositol, adenosine.
The invention mainly uses polylactic acid as a shell layer and is assisted with polycaprolactone and the like to coat the minoxidil core layer; when the injection is filled into dermal tissue to cause biostimulation reaction of organism, after injection, it is first covered by giant cells, giant cells and other lymphocytes, and then causes slight inflammatory reaction within several months, so as to stimulate human body to produce new collagen and other connective tissue collagen, and repair head skin damaged by alopecia. Minoxidil is loaded in the microsphere to enable the medicine to be slowly released at the scalp and accurately administered;
In order to further improve the drug effect and the slow release effect of minoxidil, the invention improves the uniformity of a dispersion medium, avoids sedimentation and improves the injection effect, and specifically, the invention firstly uses a temperature sensitive material, uniformly mixes with minoxidil liquid drops under high temperature conditions, then cools the solution to form temperature sensitive inner core balls for coating the minoxidil liquid drops, then adds the temperature sensitive inner core balls into an O/W environment formed by a polylactic acid and other shell material solution and a polyvinyl alcohol solution, adds temperature sensitive material particles with the particle size of 0.1-1 mu m, and after an organic solvent is completely volatilized, the polylactic acid and other shell materials and the temperature sensitive materials are gathered on the surface of the temperature sensitive inner core balls in a staggered manner to form a shell; then the temperature of the solution is raised to enable the temperature-sensitive materials in the inner core ball and the outer shell to flow out to form the drug-carrying microsphere with a core-shell structure taking minoxidil as a core layer and polylactic acid and other shell materials as shell layers, and the shell layers are provided with loose and porous pores, so that the drug carrying rate is greatly improved, the shell layers are formed into a loose and porous structure by using the temperature-sensitive materials, the porosity of the shell layers is increased, the density is reduced, the drug-carrying microsphere is not easy to settle in the solution, and meanwhile, the large porosity can improve the drug release effect.
More specifically, the preparation method of the injectable hair growth composition comprises the following steps:
1) Dissolving a shell material in an organic solvent (such as dichloromethane or chloroform) to form an oil phase solution with the concentration of 5-15%;
2) Dissolving polyvinyl alcohol in the aqueous solution to obtain 0.5-2% of aqueous solution of polyvinyl alcohol;
3) Heating to 55-60 ℃, adding 0.5-1.5% of temperature-sensitive material and 0.5-1.5% of minoxidil into the aqueous solution, stirring at a high speed to form uniform liquid drops, and then cooling to 18-20 ℃ under stirring to form temperature-sensitive inner core balls wrapping the minoxidil liquid drops;
4) Adding the temperature-sensitive inner core balls coated with minoxidil liquid drops and the oil phase solution obtained in the step 1) into the aqueous solution of the polyvinyl alcohol obtained in the step 2), stirring at the same time, adding a temperature-sensitive material with the particle size of 0.1-1 mu m, forming an oil-in-water emulsion, continuously stirring, heating the solution after the organic solvent volatilizes, cooling to room temperature, centrifuging, discarding the supernatant, washing 3 times with deionized water, adding a small amount of deionized water to redisperse the solid, and freeze-drying to obtain the core-shell microspheres;
5) Dissolving 0.5-0.7% of sodium hyaluronate, 0.5-0.7% of polydeoxyribonucleotide, 0.1-0.3% of amino acid and derivatives thereof, 0-0.3% of vitamin and derivatives thereof, 0-0.3% of trace elements and 0-0.3% of bioactive molecules in water to obtain a base solution;
6) Dispersing 5-20% of powder of the core-shell microspheres in the substrate solution prepared in the step 5) to obtain the injectable hair growth composition.
Further, the temperature sensitive material may be selected from polyethylene glycol 2000.
An application of the injectable hair growth composition in preparing medicine for treating alopecia is provided.
After the composition provided by the invention is injected into a scalp alopecia part, sodium hyaluronate and other nutrient substances provide nutrition for the skin of the head and repair damaged barriers, so that the scalp health is improved. The sodium hyaluronate provides water for the skin of the head, and is assisted with a certain antibacterial and anti-inflammatory effect, and the polydeoxyribonucleotide can identify human body signals to perform accurate skin regeneration and repair, so that a repair function is provided for damaged hair follicles; amino acids and biotin provide nutrition for hair growth, induce and promote protein synthesis and secretion, regulate cell keratinization speed and dilate epidermal capillary blood vessel, promote blood circulation, activate hair matrix cells, shorten abnormal telogen phase of hair, effectively inhibit secretion of sebaceous glands, and improve physiological functions of hair follicles so as to achieve the effects of preventing and treating alopecia and promoting hair growth. On the other hand, the shell material microspheres such as polylactic acid cause biological stimulation reaction of organisms, are firstly wrapped by lymphocytes such as giant cells and the like after injection, cause slight inflammatory reaction within a few months, stimulate human bodies to generate new collagen and other connective tissue collagen, and further repair head skin damaged by alopecia. Along with the gradual degradation of shell materials such as polylactic acid, polycaprolactone and the like in vivo, the shell materials are finally metabolized into carbon dioxide and water by a human body. Throughout the treatment cycle minoxidil as a core layer is slowly released through the pores of polylactic acid, shortening the telogen phase of the hair loss site, opening potassium ion channels, promoting proliferation of hair follicle cells.
Example 1
A method of preparing an injectable hair growth composition comprising the steps of:
1) Weighing polylactic acid and dissolving in dichloromethane to form a 5% oil phase solution;
2) Dissolving polyvinyl alcohol in the aqueous solution to prepare an aqueous solution of 1% polyvinyl alcohol;
3) Heating to 60 ℃, adding 1% of polyethylene glycol 2000 and 0.5% of minoxidil into an aqueous solution, stirring at a high speed to form uniform liquid drops, and then cooling under stirring to form temperature-sensitive inner core balls wrapping the minoxidil liquid drops;
4) Adding the temperature-sensitive inner core ball wrapped with minoxidil liquid drops and the oil phase solution into the stirred aqueous solution of polyvinyl alcohol, adding polyethylene glycol 2000 with the particle size of 0.1 mu m to form an oil-in-water emulsion, continuing stirring, heating the solution after the methylene dichloride is completely volatilized, cooling to room temperature, centrifuging, discarding supernatant, washing with deionized water for 3 times, adding a small amount of deionized water to redisperse solids, and freeze-drying to obtain the minoxidil-coated polylactic acid core-shell microsphere taking minoxidil as a core and loosening porous polylactic acid as a shell;
5) Dissolving 0.5% sodium hyaluronate, 0.5% polydeoxyribonucleotide, 0.1% arginine, 0.1% methionine, 0.1% lysine, 0.1% cysteine, 0.1% glycine, 0.1% alanine, 0.1% proline and 0.05% vitamin H in water to obtain a base solution;
6) Dispersing 5% of the powder of core-shell microspheres in the base solution 5) to obtain the composition.
Example 2
This embodiment differs from embodiment 1 in that: in the step 1), the shell material is polylactic acid and polycaprolactone; in step 3), 2% of polyethylene glycol 2000 and 0.6% of minoxidil are added; step 5) also included 0.1% zinc gluconate, 0.1% tripeptide-1 copper.
Example 3
This embodiment differs from embodiment 1 in that: in the step 1), the shell layer material is polylactic acid and polyglycolide lactide; in step 3), 1.5% of polyethylene glycol 2000 and 0.7% of minoxidil are added; step 5) also included 0.1% zinc sulfate, 0.1% myo-inositol.
Example 4
This embodiment differs from embodiment 1 in that: in the step 1), the shell material is polyethylene glycol-poly-L-lactic acid; in step 3), 2% polyethylene glycol 2000 and 0.8% minoxidil are added.
Example 5
This embodiment differs from embodiment 1 in that: in the step 1), the shell layer material is polyethylene glycol-polyglycolide lactide; in step 3), 1.5% polyethylene glycol 2000 and 0.8% minoxidil were added.
Example 6
This embodiment differs from embodiment 1 in that: in step 5), the base solution comprises: 0.6% sodium hyaluronate, 0.7% polydeoxyribonucleotide, 0.1% arginine, 0.1% tyrosine, 0.1% aspartic acid and 0.1% vitamin B2, 0.1% zinc chloride, 0.1% acetyltetrapeptide-3.
Example 7
This embodiment differs from embodiment 1 in that: in step 5), the base solution comprises: 0.7% sodium hyaluronate, 0.6% polydeoxyribonucleotide, 0.1% citrulline, 0.1% alanine, 0.1% proline and 0.1% vitamin C, 0.1% zinc pyrithione, 0.1% sphinganine.
Example 8
This embodiment differs from embodiment 1 in that: in step 6), 10% of the powder of core-shell microspheres is dispersed in the base solution.
Example 9
This embodiment differs from embodiment 1 in that: in step 6), 15% of the powder of core-shell microspheres is dispersed in the base solution.
Comparative example 1
The preparation method of the injectable hair growth composition in the comparative example comprises the following steps:
1) Weighing polylactic acid and dissolving the polylactic acid in dichloromethane to form a 5% oil phase solution;
2) Dissolving polyvinyl alcohol in the aqueous solution to prepare an aqueous solution of 1% polyvinyl alcohol;
3) Adding 0.5% minoxidil into the aqueous solution of polyvinyl alcohol, and continuously stirring to obtain a polyvinyl alcohol solution;
4) Dropwise adding the oil phase solution obtained in the step 1) into the stirring polyvinyl alcohol solution obtained in the step 3) to form an oil-in-water emulsion, continuously stirring, centrifuging after the methylene dichloride is completely volatilized, discarding the supernatant, washing 3 times by using deionized water, adding a small amount of deionized water to redisperse the solid, and freeze-drying to obtain the minoxidil-loaded polylactic acid microsphere;
5) Obtaining a base solution from 0.5% sodium hyaluronate, 0.5% polydeoxyribonucleotide, 0.1% arginine, 0.1% methionine, 0.1% lysine, 0.1% cysteine, 0.1% glycine, 0.1% alanine, 0.1% proline and 0.05% vitamin H water;
6) 5% of minoxidil-loaded polylactic acid microsphere powder was dispersed in a base solution to obtain an injectable hair growth composition containing minoxidil.
Experimental example 1 physical Property detection
The average particle diameter, the encapsulation efficiency, the drug loading rate, the sedimentation effect, the pushing force of the syringe handle and the slow release effect are tested for each example and comparative example; the detection results are shown in Table 1:
Wherein, encapsulation efficiency = drug loading/dose x 100%;
Drug loading = drug mass in microsphere/microsphere mass x 100%;
The sedimentation effect detection method comprises the following steps: loading the obtained sample into a centrifuge tube, centrifuging under the same state, and observing whether sedimentation exists or not;
The method for detecting the pushing force of the syringe handle comprises the following steps: filling a sample into a prefilled syringe, installing a 30G disposable sterile injection needle, installing a push rod and a booster, simulating actual use conditions, pushing the push rod at a constant speed of 30 mm/min, and pushing the sample in the syringe out through a needle to obtain a pushing force curve; recording a pushing force curve of the platform area;
The slow release effect detection method comprises the following steps: 0.2ml of the sample of example 3 and 0.2ml of the sample of comparative example were injected subcutaneously into mice, and after a period of time, the tissue at the injection site was taken, and the content of remaining minoxidil was detected, whereby the sustained release rate in each period of time was determined as sustained release rate= (injection amount-remaining amount)/injection amount×100%.
TABLE 1 average particle size, encapsulation efficiency, drug loading rate, sedimentation effect and results of the syringe handle push force test
| Average particle diameter (μm) | Encapsulation efficiency (%) | Drug loading rate (%) | Whether or not to settle | Push force of syringe handle (N) | |
| Example 1 | 36.4 | 99.2 | 62.5 | Whether or not | 12.4 |
| Example 2 | 37.5 | 99.4 | 61.3 | Whether or not | 12.2 |
| Example 3 | 39.5 | 99.3 | 68.5 | Whether or not | 12.3 |
| Example 4 | 41.5 | 98.9 | 62.8 | Whether or not | 18.4 |
| Example 5 | 41.5 | 99.5 | 68.3 | Whether or not | 20.0 |
| Example 6 | 36.5 | 98.7 | 68.4 | Whether or not | 18.4 |
| Example 7 | 36.5 | 98.9 | 68.1 | Whether or not | 20.4 |
| Example 8 | 36.5 | 98.8 | 68.0 | Whether or not | 21.3 |
| Example 9 | 36.5 | 99.1 | 66.4 | Whether or not | 28.4 |
| Comparative example 1 | 36.4 | 15.3 | 12.5 | Is that | 40.3 |
From the results of each example and comparative example, increasing the amount of minoxidil added increases the final particle size of the microspheres; the content of the microspheres is increased, the pushing force of the syringe handle is also increased, but no sedimentation phenomenon occurs; in addition, the encapsulation rate of the medicines in each embodiment of the invention is more than 98 percent and is close to 100 percent, the medicine carrying rate is also more than 50 percent, and the average particle size of microspheres can be increased by increasing the feeding amount of minoxidil, the medicine carrying rate is reduced, and the pushing force of a syringe handle is increased; the encapsulation rate of the comparative example is only 15.3%, the drug loading rate is only 12.5%, sedimentation phenomenon occurs, and the pushing force of the syringe handle is larger due to uneven dispersion of the microspheres in the solution, so that the operation difficulty is increased in the actual treatment process, and the injected drugs are uneven, so that the final drug effect is influenced.
Experimental example 2 sustained Release assay
The results of the sustained release tests of the drugs in example 3 and comparative example 1 are shown in fig. 1, and as can be seen from fig. 1, the core-shell drug-loaded microsphere provided by the invention only releases 17.5% after 50 days of injection, and has no obvious burst release and good sustained release effect. The solid drug-loaded microsphere prepared in comparative example 1 showed obvious burst release after 7 days of injection, and the release was nearly 100% within 35 days. This is because the drug carrier of the solid microspheres is adsorbed only on the surface of the microspheres, and is suddenly released by the stimulation of microenvironment after being injected into the body. The core-shell microsphere provided by the invention directly takes the medicine as a core layer and takes the degradable material as a shell layer structure, and the surface of the core-shell microsphere is provided with a loose and porous gap structure, so that the medicine carrying rate is greatly improved, and the slow release effect is more outstanding.
Experimental example 3 animal experiment
After 24C 57BL/6J male mice are adaptively fed for 3d, testosterone propionate is injected into subcutaneous parts of each mouse at a dose of 5mg/kg/d for 5 weeks, and an animal model of seborrheic alopecia is established.
After the modeling period is over, the modeling C57BL/6J male mice are randomly divided into 3 groups, namely a sample group, a smear control group and a blank control group, and 8 mice in each group (2 mice for later use). The mice were dehaired with a dehairing paste with a dehairing area of 2cm×3cm. Testosterone propionate injection was continued for each group of mice. Using the composition obtained in example 3 as an animal experiment sample, the sample set was injected into the back dehairing area, and 0.1ml of the sample was injected into the subcutaneous site in a lattice technique, and only one injection was performed. The depilatory areas of the control were applied with commercially available minoxidil tincture (0.5% strength), 0.1 ml/dose, once every 3 days. The dehairing area of the control mice group was injected subcutaneously with saline in a matrix of 0.1 ml/mouse, with only one injection for 3 consecutive weeks.
Daily photographic observations and recordings of hair growth (1-21 days) were made on the mice, and the results are shown in fig. 2, in which the back skin of each group of mice appeared pink after the hair was removed by modeling, and the corresponding treatments were performed on each group of mice. For each sample group of mice, 0.1ml of the composition shown in example 3 was injected into the subcutaneous site, and over time the sample group began on day 7 and the skin began to appear significantly deeper on the back of the dehaired site, starting on day 14 and the back hair had become very dense. The commercial minoxidil tincture (with the concentration of 0.5%) is smeared on the control group, 0.1 ml/mouse is smeared once every 3 days, and the back skin of the mouse smeared on the control group is obviously deepened by 11 days; at the same time, mice in the control group, which had been subcutaneously injected with physiological saline, had slow and uneven hair growth. From the back hair growth condition of mice in the C57BL/6J animal experiment, the composition provided by the invention has the most obvious effect of promoting hair growth, and the effect is obviously better than that of the minoxidil tincture which is applied on the market by 5%.
From day four, mice were scored for hair growth, with the scoring rules set forth in table 2 below:
TABLE 2 Hair scoring rules
| Growth conditions | Integration of growth |
| The skin is pink | 0 |
| The skin is gray | 1 |
| The skin is black | 2 |
| The skin is black, and has little hair growth | 3 |
| The hair is dense and has a length of about half of the unhairing area | 4 |
| The hair is dense, and the hair length is consistent with the hair removal area | 5 |
The scoring and scoring (4-21 days) of back hair growth for each group of mice are shown in table 3 and fig. 3:
TABLE 3 Back hair growth score for mice of each group
Note that: for analysis of the results on day 21, the comparison of P <0.05 for the sample and the control, and P <0.05 for the control and the control, all had significant differences, and the differences were statistically significant.
From the results of table 3 and fig. 3, it can be seen that: after modeling and different treatments of C57BL/6J male mice, the sample group showed excellent hair growth effects compared with both the smear control group and the blank control group; and minoxidil tincture applied to the control group grew slower than the sample group. From this, it can be seen that: the composition provided by the invention has good hair growth promoting effect.
The above is only a preferred embodiment of the present invention, and is not intended to limit the present invention, but various modifications and variations can be made to the present invention by those skilled in the art. Any modification, equivalent replacement, improvement, etc. made within the spirit and principle of the present invention should be included in the protection scope of the present invention.
Claims (10)
1. An injectable hair tonic composition comprising the following components: core-shell microspheres, sodium hyaluronate and polydeoxyribonucleotide coated with minoxidil core layer by using shell layer;
the preparation method of the core-shell microsphere comprises the following steps:
1) Dissolving a shell material in an organic solvent to form an oil phase solution;
2) Dissolving polyvinyl alcohol in the aqueous solution to obtain an aqueous solution of polyvinyl alcohol;
3) Under the heating condition, adding a temperature-sensitive material and minoxidil into an aqueous solution, stirring at a high speed to form liquid drops, and then cooling under the stirring condition to form a temperature-sensitive inner core ball wrapping the minoxidil liquid drops;
4) Adding the temperature-sensitive inner core ball coated with the minoxidil liquid drop obtained in the step 3) and the oil phase solution obtained in the step 1) into the aqueous solution of the polyvinyl alcohol obtained in the step 2), stirring at the same time, adding a temperature-sensitive material to form an oil-in-water emulsion, continuously stirring, heating the solution after the organic solvent volatilizes, cooling to room temperature, and treating to obtain the core-shell microsphere coated with the minoxidil core layer by the shell layer.
2. The injectable hair growth composition of claim 1, wherein the shell layer of the core-shell microsphere comprises: one or more of polylactic acid, polyglycolide, polycaprolactone, polyethylene glycol-poly-L-lactic acid, polyethylene glycol-polyglycolide or polyethylene glycol-polycaprolactone.
3. The injectable hair growth composition according to claim 1 or 2, further comprising: amino acids and their derivatives, vitamins and their derivatives, trace elements, and bioactive molecules.
4. The injectable hair growth composition according to claim 3, wherein the mass ratio of the core-shell microspheres, sodium hyaluronate, polydeoxyribonucleotides, amino acids and derivatives thereof, vitamins and derivatives thereof, trace elements, bioactive molecules is: 5-20%, 0.5-0.7%, 0.1-1.0%, 0-0.3%; the balance being water.
5. The injectable hair growth composition of claim 4 wherein the amino acids and derivatives thereof include, but are not limited to, the following components: arginine, ornithine, citrulline, acetylmethionine, acetylcysteine, lysine, methionine, tyrosine, cystine, cysteine, alpha-aminobutyric acid, alanine, asparagine, aspartic acid, glutamine, glutamic acid, glycine, histidine, hydroxyproline, isoleucine, leucine, phenylalanine, proline, serine, taurine, threonine, tryptophan, valine; the vitamins and their derivatives include, but are not limited to, the following components: one or more of vitamin C, vitamin B, vitamin H, and tocopheryl acetate; the microelements comprise, but are not limited to, one or more of zinc gluconate, zinc chloride, zinc sulfate, zinc carbonate and zinc pyrithione.
6. The injectable hair growth composition of claim 4, wherein the bioactive molecule includes, but is not limited to: one or more of tripeptide-1 copper, biotin tripeptide-1, acetyltetrapeptide-3, sphinganine, pyrrolidinyl diaminopyrimidine oxide, myo-inositol, and adenosine.
7. A method of preparing an injectable hair growth composition according to any one of claims 1 to 6, comprising the steps of:
1) Dissolving a shell material in an organic solvent to form an oil phase solution;
2) Dissolving polyvinyl alcohol in the aqueous solution to obtain an aqueous solution of polyvinyl alcohol;
3) Under the heating condition, adding a temperature-sensitive material and minoxidil into an aqueous solution, stirring at a high speed to form liquid drops, and then cooling under the stirring condition to form a temperature-sensitive inner core ball wrapping the minoxidil liquid drops;
4) Adding the temperature-sensitive inner core spheres coated with minoxidil liquid drops obtained in the step 3) and the oil phase solution obtained in the step 1) into the aqueous solution of the polyvinyl alcohol obtained in the step 2), stirring at the same time, adding a temperature-sensitive material to form an oil-in-water emulsion, continuously stirring, heating the solution after the organic solvent volatilizes, cooling to room temperature, and treating to obtain core-shell microspheres coated with minoxidil core layers by shell layers;
5) Dissolving sodium hyaluronate and polydeoxyribonucleotide in water to obtain a base solution;
6) Dispersing the microsphere powder of the core-shell microsphere of which the shell layer is used for coating the minoxidil core layer, which is obtained in the step 4), in the substrate solution which is obtained in the step 5), so as to obtain the injectable hair growing composition.
8. The method for preparing an injectable hair growth composition according to claim 7, wherein the preparing of the base solution in step 5) further comprises the steps of: adding one or more of amino acids and their derivatives, vitamins and their derivatives, microelements, and bioactive molecules.
9. The method of preparing an injectable hair growth composition according to claim 7, wherein the temperature sensitive material is polyethylene glycol.
10. Use of an injectable hair growth composition according to any one of claims 1 to 6 or prepared by a method according to any one of claims 7 to 9 in the manufacture of a medicament for treating hair loss.
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