CN115844809B - Microneedle for treating alopecia and preparation method thereof - Google Patents
Microneedle for treating alopecia and preparation method thereof Download PDFInfo
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- CN115844809B CN115844809B CN202310124145.1A CN202310124145A CN115844809B CN 115844809 B CN115844809 B CN 115844809B CN 202310124145 A CN202310124145 A CN 202310124145A CN 115844809 B CN115844809 B CN 115844809B
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Classifications
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- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
- Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
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Abstract
The invention relates to the technical field of hair growth, in particular to a microneedle for treating alopecia and a preparation method thereof, the method comprises the steps of mixing tretinoin, benzenode, spironolactone, finasteride, minoxidil, A-type botulinum toxin, impatiens extract, henna extract and cerium oxide-loaded nano enzyme to prepare a mixed solution, adding sodium hyaluronate to prepare a microneedle needle matrix solution A, mixing a silk fibroin solution, proline, serine and glycine to obtain a microneedle needle matrix solution B, preparing PVP-K90 solution as a microneedle back lining matrix solution C, and coating the microneedle needle matrix solution B in a PDMS groove; taking a microneedle body matrix solution A, placing the microneedle body matrix solution A in a cavity with a groove of a PDMS groove, dripping the microneedle backing matrix solution C on the surface of a mould, and centrifuging to separate the microneedle body matrix solution A by self; the length of the microneedle prepared by the method is 0.5mm, and the microneedle has good hair growth effect and anti-inflammatory effect.
Description
Technical Field
The invention relates to the technical field of hair growth, in particular to a microneedle for treating alopecia and a preparation method thereof.
Background
Androgenic alopecia is the most common chronic alopecia disorder in today's society, characterized by progressive hair follicle miniaturization. Epidemiological investigation results show that the incidence rate of AGA in China has sex difference, the incidence rate of AGA in men is 15-19%, the incidence rate of AGA in women is 3-5%, AGA usually starts to occur in puberty, the incidence rate gradually increases with age, different degrees of mental affective disorder such as spelt, anxiety, depression and the like are often caused, the quality of life and mental health of a plurality of patients are negatively influenced, and the AGA becomes particularly obvious in young patients.
Investigation data show that the alopecia crowd in China reaches up to 1.6 hundred million. In men, every 4 people have a problem of alopecia, and the problem of alopecia is increasingly emphasized as the aging of alopecia people is increasingly obvious due to the effects of external factors such as serious environmental pollution, irregular diet, large working pressure and the like, and the health and beauty consciousness of the public is increasingly strong.
The hair loss is classified into normal hair loss and pathological hair loss according to the cause. The normal alopecia is hair loss in the withdrawal period or the resting period, 70-100 hairs of a normal person are shed every day, and the hair loss is caused by metabolism of scalp hair follicle cells and belongs to normal metabolism of a human body; the pathological alopecia refers to alopecia caused by insufficient nutrition of hair due to degeneration of normal hair follicle cells or entering telogen phase. Pathological alopecia often results in the occurrence of baldness, alopecia areata, etc.
Aiming at the continuous increase of pathological alopecia crowds, various alopecia prevention products appear on the market. The products can be approximately divided into two types, one type of products is based on the traditional Chinese medicine theory, and composite herbal extracts are adopted to correspondingly produce effects of nourishing or controlling oil and the like according to different formula raw materials so as to achieve the purpose of preventing alopecia, but most of the products have insignificant effects from the analysis of feedback after use by consumers; another product is a hair care product added with western medicines, and the product has obvious hair loss prevention and hair growth effects in the initial use period, but has obvious side effects (sexual dysfunction, hypotension and the like) after long-term use, so that the hair care product cannot be lost. Therefore, more convenient and effective hair-loss prevention and hair-growing methods are still required.
Disclosure of Invention
Aiming at the defects of the prior art, the invention aims to provide a microneedle for treating alopecia and a preparation method thereof, so as to solve the problems of poor hair loss prevention and hair growth effect at present.
In order to solve the problems, the invention adopts the following technical scheme:
in a first aspect, the present invention provides a composition for preparing a microneedle for treating alopecia, comprising:
0.1-3 parts by weight of tretinoin;
0.5-5 parts by weight of benzenones;
0.1 to 1 part by weight of spirolactone;
0.1-2 parts by weight of finasteride;
1-10 parts by weight of minoxidil;
0.1-2 parts by weight of botulinum toxin type A;
0.5-2 parts by weight of impatiens balsamina extract;
0.5-2 parts by weight of a Lawsonia inermis extract;
0.5-2 parts by weight of henna extract;
0.3-5 parts by weight of cerium oxide-carrying nano enzyme.
Further, the composition for preparing a microneedle for treating alopecia comprises:
0.5 parts by weight of tretinoin;
1 part by weight of diphenyl propenone;
0.6 parts by weight of spironolactone;
0.3 parts by weight of finasteride;
5 parts by weight of minoxidil;
1.2 parts by weight of botulinum toxin A;
0.8 parts by weight of impatiens balsamina extract;
0.8 parts by weight of a Lawsonia inermis extract;
0.8 parts by weight of henna extract;
3 parts by weight of cerium oxide-loaded nano enzyme.
Further, a silk fibroin mixed solution is also included, the silk fibroin mixed solution includes:
3-12 parts by weight of a silk fibroin solution;
0.3 to 1.2 parts by weight of proline;
0.3 to 1.2 parts by weight of serine;
0.3 to 1.2 parts by weight of glycine.
Further, a silk fibroin mixed solution is also included, the silk fibroin mixed solution includes:
10 parts by weight of a silk fibroin solution;
1 part by weight of proline;
1 part by weight of serine;
1 part by weight of glycine.
Further, the preparation method of the cerium oxide-loaded nano enzyme comprises the following steps:
dissolving cerium acetate hydrate and oleylamine in dimethylbenzene, stirring at room temperature, then placing in an argon environment, heating to 90+/-10 ℃, injecting deionized water into a reaction liquid under the stirring condition, keeping the reaction liquid at 90+/-10 ℃ until the reaction liquid becomes light yellow transparent liquid, cooling to room temperature to obtain cerium oxide nanoparticles, adding acetone to precipitate the cerium oxide nanoparticles, and centrifuging to remove supernatant to wash out impurities;
dispersing cerium oxide nano particles in chloroform, adding DSPE-mPEG2000, uniformly mixing, removing chloroform by rotary evaporation at 60+/-10 ℃, and finally adding deionized water to resuspend the DSPE-mPEG2000 modified cerium oxide nano particles to obtain the cerium oxide nano enzyme.
Further, the mass ratio of the cerium acetate hydrate to the oleylamine to the dimethylbenzene is 0.3-0.5:3-4:15; deionized water is injected into the reaction liquid under the stirring condition, and the mass ratio of the deionized water to the dimethylbenzene is 1-2:15.
Further, the mass ratio of cerium acetate hydrate, oleylamine and xylene is 0.43:3.25:15; deionized water was injected into the reaction solution under stirring, and the mass ratio of deionized water to xylene was 1:15.
Further, the mass ratio of the cerium oxide nanoparticle to chloroform to the DSPE-mPEG2000 is 1-2:1-2:4.
further, the mass ratio of the cerium oxide nanoparticle, chloroform and the DSPE-mPEG2000 is 1:1:4.
in a second aspect, the present invention provides a method for preparing a microneedle for treating alopecia, comprising:
mixing tretinoin, benzenode, spirolactone, finasteride, minoxidil, A-type botulinum toxin, impatiens balsamina extract, henna extract and cerium oxide-loaded nano enzyme to obtain a mixed solution, adding sodium hyaluronate into the mixed solution, stirring, centrifuging to remove bubbles, and obtaining a microneedle body matrix solution A;
mixing a silk fibroin solution, proline, serine and glycine to obtain a microneedle needle matrix solution B;
preparing 0.3-0.5g/ml PVP-K90 solution, centrifuging to obtain air bubbles, and taking the air bubbles as microneedle backing matrix solution C.
Coating the microneedle body matrix solution B in a groove of the PDMS groove, and drying at room temperature;
and placing the microneedle needle matrix solution A on one side of a groove of the PDMS groove, centrifuging to enable the microneedle needle matrix solution A to enter a cavity of a mould, scraping off redundant solution on the surface of the mould, dripping the microneedle back lining matrix solution C on the surface of the mould after drying at room temperature, centrifuging to form a back lining layer, drying the mould for 12-30 hours, and evacuating again to continue drying until the microneedles are separated from the mould by themselves.
Further, the mass concentration of the mixed solution is 3-50mg/ml; the mass ratio of the mixed solution to the sodium hyaluronate is 1:0.5-3.
Further, the mass concentration of the mixed solution is 3-10mg/ml.
Further, the length of the needle body of the microneedle is greater than 0.3mm.
Further, the length of the needle body of the microneedle is 0.3-2mm.
Further, the length of the needle body of the microneedle is 0.5mm.
In a third aspect, the present invention provides a microneedle prepared by the method for preparing a microneedle for treating alopecia.
The invention has the beneficial effects that: compared with the common micro-needle, the micro-needle and the preparation method provided by the invention have more excellent hair growing effect, the micro-needle formula also has a certain anti-inflammatory and antibacterial effect, the inner layer is a sodium hyaluronate-coated medicament, and the outer layer is a silk fibroin mixed layer, so that the micro-needle has a good puncture effect, silk fibroin is degraded in the body, the medicament in the sodium hyaluronate is slowly released, and long-time treatment on a hair loss area can be realized; and by utilizing the excellent biological material characteristics of the silk fibroin, the activity of biological medicine components remained in the silk fibroin matrix can be preserved and maintained, the degradation rate of the silk fibroin and the diffusion of embedded active components are realized, and the medicine components can be effectively guided into the skin in a microneedle mode, so that the effect is better and the action effect is longer. The silk fibroin has excellent mechanical properties in a dry state, is easy to penetrate into the skin to exert drug effects, is a polymer high molecular material, has good compatibility to organisms, and has no great influence after being left in the body.
Detailed Description
The present invention will be described in further detail with reference to specific examples.
It should be noted that these examples are only for illustrating the present invention, and not for limiting the present invention, and simple modifications of the method under the premise of the inventive concept are all within the scope of the claimed invention.
A composition for preparing a microneedle for treating alopecia comprising:
0.1-3 parts by weight of tretinoin;
0.5-5 parts by weight of benzenones;
0.1 to 1 part by weight of spirolactone;
0.1-2 parts by weight of finasteride;
1-10 parts by weight of minoxidil;
0.1-2 parts by weight of botulinum toxin type A;
0.5-2 parts by weight of impatiens balsamina extract;
0.5-2 parts by weight of a Lawsonia inermis extract;
0.5-2 parts by weight of henna extract;
0.3-5 parts by weight of cerium oxide-carrying nano enzyme.
As an embodiment, a composition for preparing a microneedle for treating alopecia, comprising:
0.5 parts by weight of tretinoin;
1 part by weight of diphenyl propenone;
0.6 parts by weight of spironolactone;
0.3 parts by weight of finasteride;
5 parts by weight of minoxidil;
1.2 parts by weight of botulinum toxin A;
0.8 parts by weight of impatiens balsamina extract;
0.8 parts by weight of a Lawsonia inermis extract;
0.8 parts by weight of henna extract;
3 parts by weight of cerium oxide-loaded nano enzyme.
As an embodiment, a composition for preparing a microneedle for treating alopecia further includes a silk fibroin mixed solution including:
3-12 parts by weight of a silk fibroin solution;
0.3 to 1.2 parts by weight of proline;
0.3 to 1.2 parts by weight of serine;
0.3 to 1.2 parts by weight of glycine.
More preferably, the silk fibroin mixed solution comprises:
10 parts by weight of a silk fibroin solution;
1 part by weight of proline;
1 part by weight of serine;
1 part by weight of glycine.
The impatiens balsamina is used as an ornamental plant primer in areas such as Europe, asia, america and the like, is also a medicinal plant, can extract active ingredients with various pharmacological activities such as naphthoquinone, flavonoid, coumarin and the like, can play roles of resisting bacteria, allergy, itching, inflammation and the like, is traditionally used for treating stabs, abscesses, chronic ulcers and the like, contains various coloring ingredients, and has been widely applied to the cosmetic fields such as hair dyeing and the like. The active ingredients of the garden balsam can inhibit the activity of testosterone 5 alpha reductase, and the invention utilizes the above-mentioned effects of the garden balsam to inhibit the conversion of testosterone dihydrotestosterone and reduce the content of dihydrotestosterone around hair follicle, thereby treating alopecia.
The henna can extract active substances such as coumarin, flavonoid, naphthoquinone, quinine, organic acid, phenol and the like, has strong functions of resisting oxidation, resisting inflammation, relieving fever and pain, protecting liver, promoting urination, reducing blood glucose and the like, has a certain similarity with the pharmacological actions of garden balsam, and belongs to different subjects. The invention uses the lawns to treat alopecia and can eliminate the serious effect of wound parts.
Botulinum toxin is a neurotoxic toxin produced by gram-positive clostridium botulinum during the process of growth replication and is mainly used at muscle junctions to prevent neurotransmission between peripheral nerve endings and muscle fibers by inhibiting release of the neuromediator acetylcholine from the pre-herniated nerve membranes, thereby causing muscle relaxation type paralysis. The invention is used for treating alopecia, and reduces the muscle pressure of scalp perforation blood vessels by relaxing scalp muscles, thereby increasing the blood perfusion of scalp at a specific alopecia part, the increase of blood flow is helpful for removing local accumulated DHT, in addition, the local injection of A-type botulinum toxin can increase blood oxygenation, the extraction of oxygen content is favorable for promoting the conversion of testosterone into estradiol, inhibiting the generation of DHT and promoting the hair follicle to enter into the growing period. The increase in chemical perfusion and the increase in oxygen content reduce DHT concentration, alleviate the effect of androgens on susceptible hair follicles, inhibit hair follicle micromation, and thereby reduce hair loss.
The invention utilizes cerium oxide-loaded nano enzyme to prepare the micro needle, can remove excessive active oxygen in skin tissues, improve the oxidative stress microenvironment around hair follicles, cause mechanical stimulation of certain intensity to the skin by using the micro needle, can up regulate the expression of the epidermal growth factor in the skin, induce angiogenesis around the hair follicles and realize hair regeneration.
The preparation method of the cerium oxide-loaded nano enzyme comprises the following steps:
dissolving cerium acetate hydrate and oleylamine in dimethylbenzene, stirring at room temperature, then placing in an argon environment, heating to 90+/-10 ℃, injecting deionized water into a reaction liquid under the stirring condition, keeping the reaction liquid at 90+/-10 ℃ until the reaction liquid becomes light yellow transparent liquid, cooling to room temperature to obtain cerium oxide nanoparticles, adding acetone to precipitate the cerium oxide nanoparticles, and centrifuging to remove supernatant to wash out impurities;
dispersing cerium oxide nano particles in chloroform, adding DSPE-mPEG2000, uniformly mixing, removing chloroform by rotary evaporation at 60+/-10 ℃, and finally adding deionized water to resuspend the DSPE-mPEG2000 modified cerium oxide nano particles to obtain the cerium oxide nano enzyme.
As an embodiment, the mass ratio of cerium acetate hydrate, oleylamine and xylene is 0.3-0.5:3-4:15; deionized water is injected into the reaction liquid under the stirring condition, and the mass ratio of the deionized water to the dimethylbenzene is 1-2:15.
As an embodiment, the mass ratio of cerium acetate hydrate, oleylamine and xylene is 0.43:3.25:15; deionized water was injected into the reaction solution under stirring, and the mass ratio of deionized water to xylene was 1:15.
As an embodiment, the mass ratio of the cerium oxide nanoparticle, chloroform and DSPE-mPEG2000 is 1-2:1-2:4.
as an embodiment, the mass ratio of the cerium oxide nanoparticle, chloroform and DSPE-mPEG2000 is 1:1:4.
a method of preparing a microneedle for treating alopecia comprising:
mixing tretinoin, benzenode, spirolactone, finasteride, minoxidil, A-type botulinum toxin, impatiens balsamina extract, henna extract and cerium oxide-loaded nano enzyme to obtain a mixed solution, adding sodium hyaluronate into the mixed solution, stirring, centrifuging to remove bubbles, and obtaining a microneedle body matrix solution A;
mixing a silk fibroin solution, proline, serine and glycine to obtain a microneedle needle matrix solution B;
0.4g/ml PVP-K90 solution was prepared and the air bubbles were centrifuged to give a microneedle backing matrix solution C.
Coating the microneedle body matrix solution B in a groove of the PDMS groove, and drying at room temperature;
and placing the microneedle needle matrix solution A on one side of a groove of the PDMS groove, centrifuging to enable the microneedle needle matrix solution A to enter a cavity of a mould, scraping off redundant solution on the surface of the mould, dripping the microneedle back lining matrix solution C on the surface of the mould after drying at room temperature, centrifuging to form a back lining layer, drying the mould for 12-30 hours, and evacuating again to continue drying until the microneedles are separated from the mould by themselves.
As an embodiment, the mass concentration of the mixed solution is 3-10mg/ml; the mass ratio of the mixed solution to the sodium hyaluronate is 1:0.5-3.
As one embodiment, the microneedle has a needle length of greater than 0.3mm.
As one embodiment, the microneedle has a needle length of 0.3-2mm.
As one embodiment, the microneedle has a needle length of 0.5mm.
The inner layer of the microneedle is hyaluronic acid (coated with a drug), and the outer layer of the microneedle is silk fibroin, so that the puncture performance of the microneedle is improved, the defect that the degradation time of individual silk proteins is long is overcome, the hair-promoting substances can be played in a short time, and the substances are placed in the microneedle for slow release.
EXAMPLE 1 preparation of microneedles for treating alopecia
Mixing tretinoin, benzenode, spirolactone, finasteride, minoxidil, A-type botulinum toxin, impatiens balsamina extract, henna extract and cerium oxide-loaded nano enzyme to obtain a mixed solution, adding sodium hyaluronate into the mixed solution, stirring, centrifuging to remove bubbles, and obtaining a microneedle body matrix solution A; the mass concentration of the mixed solution is 3mg/ml; the mass ratio of the mixed solution to the sodium hyaluronate is 1:3.
Wherein the weight ratio of the tretinoin, the benzpheryl ketone, the spirolactone, the finasteride, the minoxidil, the A-type botulinum toxin, the impatiens balsamina extract, the henna extract and the cerium oxide-loaded nano enzyme is 1:5:1:1:10:1:5:5:5:5:3.
And mixing the silk fibroin solution, proline, serine and glycine to obtain the microneedle body matrix solution B.
Wherein the weight ratio of silk fibroin solution, proline, serine and glycine is 30:3:3:3.
0.3g/ml PVP-K90 solution was prepared and the air bubbles were centrifuged to give a microneedle backing matrix solution C.
And coating the microneedle body matrix solution B in the groove of the PDMS groove, and drying at room temperature.
Taking a microneedle body matrix solution A, placing the microneedle body matrix solution A on one side of a groove of a PDMS groove, centrifuging to enable the microneedle body matrix solution A to enter a cavity of a mould, scraping redundant solution on the surface of the mould, dripping a microneedle back lining matrix solution C on the surface of the mould after drying at room temperature, centrifuging to form a back lining layer, drying the mould for 12-30 hours, evacuating and continuing drying until the microneedle is separated from the mould by itself, and obtaining the microneedle, wherein the length of the microneedle body of the microneedle is 0.3mm.
EXAMPLE 2 preparation of microneedles for treating alopecia
Mixing tretinoin, benzenode, spirolactone, finasteride, minoxidil, A-type botulinum toxin, impatiens balsamina extract, henna extract and cerium oxide-loaded nano enzyme to obtain a mixed solution, adding sodium hyaluronate into the mixed solution, stirring, centrifuging and removing bubbles to obtain a microneedle needle matrix solution A, wherein the mass concentration of the mixed solution is 10mg/ml; the mass ratio of the mixed solution to the sodium hyaluronate is 1:0.5.
Wherein the weight ratio of the tretinoin, the benzpheryl ketone, the spirolactone, the finasteride, the minoxidil, the A-type botulinum toxin, the impatiens balsamina extract, the henna extract and the cerium oxide-loaded nano enzyme is 3:5:1:2:10:2:2:2:2:5.
And mixing the silk fibroin solution, proline, serine and glycine to obtain the microneedle body matrix solution B.
Wherein the weight ratio of silk fibroin solution, proline, serine and glycine is 12:0.3:0.3:0.3.
0.5g/ml PVP-K90 solution was prepared and the air bubbles were centrifuged to give a microneedle backing matrix solution C.
And coating the microneedle body matrix solution B in the groove of the PDMS groove, and drying at room temperature.
Taking a microneedle needle matrix solution A, placing the microneedle needle matrix solution A on one side of a groove of a PDMS groove, centrifuging to enable the microneedle needle matrix solution A to enter a cavity of a mould, scraping redundant solution on the surface of the mould, dripping a microneedle back lining matrix solution C on the surface of the mould after drying at room temperature, centrifuging to form a back lining layer, drying the mould for 24 hours, evacuating and continuing drying until the microneedles are separated from the mould, and obtaining the microneedles with the length of 2mm.
EXAMPLE 3 preparation of microneedles for treating alopecia
Mixing tretinoin, benzenode, spirolactone, finasteride, minoxidil, A-type botulinum toxin, impatiens balsamina extract, henna extract and cerium oxide-loaded nano enzyme to obtain a mixed solution, adding sodium hyaluronate into the mixed solution, stirring, centrifuging and removing bubbles to obtain a microneedle needle matrix solution A, wherein the mass concentration of the mixed solution is 5mg/ml; the mass ratio of the mixed solution to the sodium hyaluronate is 1:1.
Wherein the weight ratio of the tretinoin, the benzpheryl ketone, the spirolactone, the finasteride, the minoxidil, the A-type botulinum toxin, the impatiens balsamina extract, the henna extract and the cerium oxide-loaded nano enzyme is 5:10:6:3:50:12:8:8:8:30.
And mixing the silk fibroin solution, proline, serine and glycine to obtain the microneedle body matrix solution B.
Wherein the weight ratio of silk fibroin solution, proline, serine and glycine is 10:1:1:1.
0.4g/ml PVP-K90 solution was prepared and the air bubbles were centrifuged to give a microneedle backing matrix solution C.
And coating the microneedle body matrix solution B in the groove of the PDMS groove, and drying at room temperature.
Taking a microneedle needle matrix solution A, placing the microneedle needle matrix solution A on one side of a groove of a PDMS groove, centrifuging to enable the microneedle needle matrix solution A to enter a cavity of a mould, scraping redundant solution on the surface of the mould, dripping a microneedle back lining matrix solution C on the surface of the mould after drying at room temperature, centrifuging to form a back lining layer, drying the mould for 24 hours, evacuating again, continuing drying until the microneedles are separated from the mould, and obtaining the microneedles, wherein the length of the microneedle needle is 0.5mm.
EXAMPLE 4 microneedle needle sizing analysis
The micro-needle acupuncture is a minimally invasive treatment technology, and is used for generating stress reaction through needle-punched damaged skin, stimulating the generation and release of platelet-derived growth factors, epidermal growth factors and the like, activating stem cells of follicular processes, promoting hair growth, forming transdermal micro-channels after the skin is needled, and promoting the absorption of external medicines. However, the length of the microneedle body or the depth of needle penetration has an influence on the hair growth effect, so that different microneedles with the length of 0.3-2mm are prepared by using the formula of the embodiment 3, the influence of the different microneedle lengths on the hair growth is analyzed by adopting a biological test, and the curative effect of treating the hair loss by using the microneedles with the length of 0.5mm is the best after 12 weeks of treatment.
Example 5 Effect verification
The AGA model is prepared by using healthy male mice, firstly, partial hair in the center of the back of a test animal is removed, the back skin area of each mouse is about 2 x 3cm, the back skin area is dehaired by using dehaired cream, subcutaneous multipoint injection is carried out on the back dehaired area of the mouse by using testosterone propionate diluent, the total dose is 0.02 ml/mouse, and the continuous injection is carried out for 35 days once a day. And (3) carrying out pathological examination on the dehairing area on the back of the mouse, and selecting the mouse which is successfully constructed into the AGA model for testing.
The microneedles of examples 1-3 were used, and the conventional microneedles were administered to mice once daily, and the hair growth (number of hair follicles) and skin inflammation (divided into none/micro/medium/heavy) of the back dehairing area of the mice for 1 week, 2 weeks, 3 weeks, and 4 weeks were recorded according to the skin condition 1 hour after 20 minutes of drug delivery by microneedle application.
| Initial initiation | For 1 week | For 2 weeks | 3 weeks | 4 weeks of | |
| Example 1 | 22/none | 31/micro | 38/micron | 45/micro | 51/micro |
| Example 2 | 23/none | 35/micron | 40/micro | 44/micro | 49/micro |
| Example 3 | 20/none | 36/micro | 43/none | 50/none | 55/micro |
| Ordinary microneedle | 20/none | 25/micron | 28/middle | 32/middle | 34/middle |
The common microneedles are drug-free microneedles, the specific microneedles adopted are microneedle rollers, or electronic microneedles with the same principle as the microneedle rollers, and the treatment of the microneedle rollers can be seen in hundred degrees encyclopedia. The ordinary microneedle does not carry medicine, but adopts the conventional micropin to carry out microneedle roller stimulation to the mouse dehairing area.
According to the mouse experiment, the micro-needle provided by the invention has a good hair growth effect because the micro-needle is a common micro-needle without medicine, and in the process that the hair growth tends to be gentle at the 4 th week, the number of the example 3 is increased by 35, and the number of the blank groups is increased by 14. From the aspect of skin inflammation, the micro-needle drug delivery has a certain slight influence on skin, and the micro-needle formula provided by the invention has a certain disinfection, bacteriostasis and anti-inflammation effects after the micro-needle drug delivery.
Finally, it is noted that the above-mentioned embodiments illustrate rather than limit the invention, and that those skilled in the art will be understood that various changes in form and details may be made therein without departing from the spirit and scope of the invention as defined by the appended claims.
Claims (10)
1. A composition for preparing a microneedle for treating alopecia, comprising:
0.1-3 parts by weight of tretinoin;
0.5-5 parts by weight of benzenones;
0.1 to 1 part by weight of spirolactone;
0.1-2 parts by weight of finasteride;
1-10 parts by weight of minoxidil;
0.1-2 parts by weight of botulinum toxin type A;
0.5-2 parts by weight of impatiens balsamina extract;
0.5-2 parts by weight of a Lawsonia inermis extract;
0.5-2 parts by weight of henna extract;
0.3-5 parts by weight of cerium oxide-carrying nano enzyme.
2. The composition for preparing a microneedle for treating alopecia according to claim 1, comprising:
0.5 parts by weight of tretinoin;
1 part by weight of diphenyl propenone;
0.6 parts by weight of spironolactone;
0.3 parts by weight of finasteride;
5 parts by weight of minoxidil;
1.2 parts by weight of botulinum toxin A;
0.8 parts by weight of impatiens balsamina extract;
0.8 parts by weight of a Lawsonia inermis extract;
0.8 parts by weight of henna extract;
3 parts by weight of cerium oxide-loaded nano enzyme.
3. The composition for preparing a microneedle for treating alopecia of claim 1, further comprising a silk fibroin mixed solution comprising:
3-12 parts by weight of a silk fibroin solution;
0.3 to 1.2 parts by weight of proline;
0.3 to 1.2 parts by weight of serine;
0.3 to 1.2 parts by weight of glycine.
4. The composition for preparing a microneedle for treating alopecia according to claim 1, wherein the preparation method of the cerium oxide-loaded nano enzyme comprises:
dissolving cerium acetate hydrate and oleylamine in dimethylbenzene, stirring at room temperature, then placing in an argon environment, heating to 90+/-10 ℃, injecting deionized water into a reaction liquid under the stirring condition, keeping the reaction liquid at 90+/-10 ℃ until the reaction liquid becomes light yellow transparent liquid, cooling to room temperature to obtain cerium oxide nanoparticles, adding acetone to precipitate the cerium oxide nanoparticles, and centrifuging to remove supernatant to wash out impurities;
dispersing cerium oxide nano particles in chloroform, adding DSPE-mPEG2000, uniformly mixing, removing chloroform by rotary evaporation at 60+/-10 ℃, and finally adding deionized water to resuspend the DSPE-mPEG2000 modified cerium oxide nano particles to obtain the cerium oxide nano enzyme.
5. The composition for preparing a microneedle for treating alopecia according to claim 4, wherein the mass ratio of cerium acetate hydrate, oleylamine and xylene is 0.3-0.5:3-4:15; deionized water is injected into the reaction liquid under the stirring condition, and the mass ratio of the deionized water to the dimethylbenzene is 1-2:15.
6. The composition for preparing a microneedle for treating alopecia according to claim 4, wherein the mass ratio of the cerium oxide nanoparticle, chloroform and DSPE-mPEG2000 is 1-2:1-2:4.
7. a method for preparing a microneedle for treating alopecia, which is characterized by comprising the following steps:
mixing 0.1-3 parts by weight of tretinoin, 0.5-5 parts by weight of dibenzoyl acrylic ketone, 0.1-1 part by weight of spironolactone, 0.1-2 parts by weight of finasteride, 1-10 parts by weight of minoxidil, 0.1-2 parts by weight of botulinum toxin type A, 0.5-2 parts by weight of impatiens balsamina extract, 0.5-2 parts by weight of henna extract and 0.3-5 parts by weight of cerium oxide-carrying nano enzyme to prepare a mixed solution, adding sodium hyaluronate into the mixed solution, stirring, centrifuging and removing bubbles to prepare a microneedle needle matrix solution A;
mixing a silk fibroin solution, proline, serine and glycine to obtain a microneedle needle matrix solution B;
preparing 0.3-0.5g/ml PVP-K90 solution, centrifuging to obtain air bubbles, and taking the air bubbles as microneedle backing matrix solution C;
coating the microneedle body matrix solution B in a groove of the PDMS groove, and drying at room temperature;
and placing the microneedle needle matrix solution A on one side of a groove of the PDMS groove, centrifuging to enable the microneedle needle matrix solution A to enter a cavity of a mould, scraping off redundant solution on the surface of the mould, dripping the microneedle back lining matrix solution C on the surface of the mould after drying at room temperature, centrifuging to form a back lining layer, drying the mould for 12-30 hours, and evacuating again to continue drying until the microneedles are separated from the mould by themselves.
8. The method for preparing the microneedle for treating alopecia according to claim 7, wherein the mass concentration of the mixed solution is 3-50mg/ml; the mass ratio of the mixed solution to the sodium hyaluronate is 1:0.5-3.
9. The method of claim 7, wherein the length of the microneedle is greater than 0.5mm.
10. A microneedle prepared by the method for preparing a microneedle for treating alopecia according to any one of claims 7 to 9.
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