CN-121987552-A - Penetration-promoting composition of sponge microneedle-mediated different anti-alopecia active ingredients

Abstract

The invention discloses a sponge microneedle-mediated anti-hair loss active ingredient combination which can promote transdermal absorption of hair growth active ingredients. The active ingredients of the composition comprise 0.1% -6.0% of sponge microneedle subjected to scalp specific screening, 0.6% -10.0% of hair growth active substance (polygonum multiflorum extract, biota orientalis extract, ginger root extract and the like), 0.2% -6.0% of hair follicle promoting metabolic component (biotin, nicotinamide derivative, hair growth promoting peptide and the like), and the balance of aqueous component or excipient matrix. According to the invention, the sponge microneedle is used as a core-mediated carrier, a micro-channel is formed through mechanical action, simultaneously, the hair-growing active ingredients are adsorbed and slowly released, the permeation path around the hair follicle is opened, the permeation and absorption of the active ingredients to the hair follicle cell layer are enhanced, and various hair-growing active ingredients are accurately delivered to the scalp dermis and the hair follicle root cells, so that the hair follicle is activated, and the hair growth is promoted.

Inventors

• QIN HAO
• Zhang Shuchi
• QI HONGYUN
• CHEN LING
• JIANG HAIHUA

Assignees

• 秦浩
• 张舒迟
• 漆红云
• 陈玲
• 蒋海华
• 湖南晴天生物科技有限公司

Dates

Publication Date

20260508

Application Date

20260105

Claims (16)

1. 1. The sponge microneedle-mediated penetration-promoting composition for different anti-hair loss active ingredients is characterized by comprising a sponge microneedle component and a hair growth active ingredient component, wherein the mass ratio of the sponge microneedle component to the hair growth active ingredient component is 0.2% -8%: 0.5% -5%: (1) The sponge microneedle component is obtained by batch screening, wherein the screening standard is that the breakage rate is less than or equal to 10 percent, the average length is 100-220 mu m, and the sponge microneedle component is at least one selected from flaky 99% special grade (average length 182.3 mu m), mixed 99% special grade (average length 185.5 mu m) or spherical 99% special grade (average length 215.1 mu m); (2) The hair growth promoting active ingredient comprises at least 3 hair growth promoting ingredients of different molecular weight and hydrophilicity selected from minoxidil (< 500Da, amphiphilicity), retinol (< 500Da, hydrophobic), ceramide (500-1000 Da, amphiphilicity), oligopeptide-1 (< 1000Da, hydrophilic).
2. 2. The composition of claim 1, wherein the method of screening the sponge microneedle component comprises: (1) Randomly extracting at least 3 samples (each sample contains more than 100 microneedles) from each batch, observing and recording the number of broken needles by a microscope to calculate the broken needle rate, and measuring the lengths of at least 100 microneedles by a high-precision instrument to calculate the average length; (2) Puncture effect verification, namely taking fresh panama pigskin as a model, puncturing a microneedle with standard force for 30s, mixing the microneedle with VC, and then evaluating the permeation effect; (3) Screening rules, namely, batch inclusion components which meet the requirements that the needle breakage rate is less than or equal to 10 percent, the average length is more than 100 mu m and the puncture uniformity reaches the standard are simultaneously met.
3. 3. The composition of claim 1, wherein the hair growth promoting active ingredient comprises components of <500Da component 40% -60%, 500-1000Da component 30% -50%, and >1000Da component 0% -20% in different molecular weight ranges.
4. 4. The composition of claim 1, further comprising a receiver fluid assist system, wherein the receiver fluid is a PBS-ethanol mixture (volume ratio 6:4-7:3), comprises 0.5% -1% tween 80, and satisfies a sink condition (component concentration < 10% of saturated solubility).
5. 5. A process for the preparation of a composition as claimed in any one of claims 1 to 4, comprising the steps of: (1) Screening sponge microneedles, namely screening qualified sponge microneedle batches according to the method of claim 2, crushing the sponge microneedle batches to uniform particle size, and sterilizing the crushed sponge microneedle batches for later use; (2) Dissolving hair growth promoting components, mixing the hair growth promoting active components at a certain proportion, adding into physiological saline or ethanol solvent, stirring at 30-40deg.C until completely dissolving; (3) Compounding and mixing, namely slowly adding the sterilized sponge microneedle into the hair growth component solution, and stirring for 10-20min at 200-500r/min to form uniform suspension; (4) And (3) stability treatment, namely regulating the pH of the system to 6.5-7.5, adding 0.1-0.3% of preservative, aging for 72 hours at 40 ℃, and verifying that the shelf life is more than or equal to 12 months.
6. 6. A method of using the composition of any one of claims 1-4, comprising: (1) Skin pretreatment, namely cleaning a region to be treated, and removing grease and cutin; (2) The composition is applied by uniformly coating the composition on scalp or target skin area, and applying at preset pressure for 5min to form micro-channels; (3) And (3) subsequent nursing, namely flushing and natural absorption are not needed after application, and severe cleaning is avoided within 24 hours.
7. 7. The penetration promoting formula of the hair growth component based on the sponge microneedle is characterized by comprising a sponge microneedle component and a composite hair growth component, wherein the sponge microneedle is a micron-sized needle body with uniform specification, the needle content of 1g of the sponge microneedle is 500-600 ten thousand, the concentration is 0.2% -3%, and the composite hair growth component is formed by compounding a DHT inhibition component, a circulation activation component, a hair follicle restoration component and a nutrition relieving component in proportion.
8. 8. The formulation of claim 7, wherein the DHT inhibitory component is at least one of 3% Polygonum multiflorum extract, 3% Platycladus orientalis extract, or 0.3% Ammonis molecule, and the circulating activating component is at least one of 3% Zingiberaceae extract, 0.5% safflower glucoside, or 0.2% oligopeptide-1.
9. 9. The formulation of claim 7, wherein the hair follicle stimulating composition is at least one of 1% copper peptide, 0.5% apple stem cell extract, or 0.1% tripeptide-1, and the nutritional relaxing composition is at least one of 1% nicotinamide, 2% ceramide NP, or 1% centella asiatica extract.
10. 10. The formula according to claim 7, wherein the action parameters of the sponge microneedle are that the treatment time is 30s-90s, the action pressure is 0.05-0.2kg/cm < 2 >, and the needle breakage rate is less than or equal to 5%.
11. 11. A method of applying a formulation according to any one of claims 7 to 10, comprising the steps of: (1) Skin pretreatment, namely cleaning the skin of an area to be treated, and removing surface grease and impurities; (2) The formula application comprises uniformly smearing the hair growth formula containing the sponge microneedles on a target area, and gently massaging according to preset pressure and time to form micro-channels by the sponge microneedles; (3) The subsequent nursing is that the skin care can be normally carried out the next day after the low-concentration formula is used without cleaning and natural absorption after the application.
12. 12. The method of claim 11, wherein the formulation is applied at a dosage of 5-10 μl/cm2, applied to sparse scalp and hair areas, 1-2 times per week, and continuously for no less than 4 weeks.
13. 13. A transdermal efficiency detection method based on the formula of claim 7, characterized in that an isolated pig skin model and a Franz diffusion cell system are adopted to carry out a transdermal experiment at a constant temperature of 32+/-1 ℃, the concentration of components in receiving liquid at different time points is detected by an HPLC-UV method, the accumulated permeation quantity, the transdermal rate and the penetration promotion multiple are calculated, and the component retention of the epidermis and the dermis of the skin is detected.
14. 14. The method of claim 13, wherein the isolated pig skin is fresh pig back skin, is 0.5-1mm thick, is stored at 4 ℃ and is used within 6 hours, and skin integrity is verified by TEWL values (< 15g/m 2/h) prior to use.
15. 15. The method according to claim 7, wherein the receiving solution is a PBS-ethanol mixture (volume ratio 7:3), contains 0.5% Tween 80, and satisfies the condition of sink leakage (component concentration < 10% of saturated solubility).
16. 16. Use of a formulation according to any one of claims 7 to 10 in a hair tonic cosmetic, wherein the cosmetic is in the form of a cream or gel with a shelf life of not less than 36 months, meeting the requirements of cosmetic safety specifications (2015).

Description

Penetration-promoting composition of sponge microneedle-mediated different anti-alopecia active ingredients Technical Field The invention relates to the technical field of transdermal administration of cosmetics and medicines, in particular to a penetration-promoting formula which takes a sponge microneedle as a physical penetration-promoting carrier and is compounded with a specific hair-growing active ingredient, and application of the formula in development of hair-growing products, and is particularly suitable for improving the penetrating efficiency of dermis layers of hair-growing ingredients and targeting hair follicles. Background Alopecia is the decrease in hair density caused by hair follicle atrophy. The types of hair loss are classified into cicatricial hair loss, non-cicatricial hair loss and structural hair disorders. Scarring alopecia is caused by tissue damage, leading to irreversible and permanent loss of hair follicles. In non-scarring alopecia, the function of the hair follicle is inhibited in time, but can be restored by some therapeutic method, resulting in hair regrowth. The vulnerability of the hair shaft can lead to structural hair disorders. Non-scarring alopecia includes focal alopecia, diffuse alopecia, and pattern alopecia, such as male androgenetic alopecia (male pattern alopecia), female pattern alopecia, and hair-plucking. Phytochemicals are of many kinds and can be broadly classified into phenolic compounds, terpenes, terpenoids, nitrogen-containing compounds, sulfur-containing compounds, and the like. They have various physicochemical properties, biochemical characteristics and biological activities according to the difference of chemical structures. Stilbene glucoside in Polygoni Multiflori radix extract can inhibit 5α -reductase activity, and reduce Dihydrotestosterone (DHT) production, thereby preventing hair follicle atrophy caused by DHT. The anthraquinone compound can reduce the level of inflammatory factor TNF-alpha and improve the microenvironment of hair follicle by eliminating scalp free radicals. Curcumin in rhizoma Zingiberis recens extract can inhibit 5α -reductase activity, reduce DHT production, inhibit abnormal expression of Androgen Receptor (AR), and block DHT attack on hair follicle. Flavonoid components (such as quercetin and kaempferol) in folium Platycladi can competitively inhibit 5α -reductase, reduce scalp DHT level, and achieve inhibition rate similar to finasteride but lower irritation. Although various drugs have been effective in preventing hair loss and promoting hair growth, the scalp is essentially a strong defense barrier, the skin cuticle barrier and hair follicle structure severely limit the effective penetration of traditional spread hair-growing products, in which active ingredients only penetrate the cuticle of the epidermis, the cuticle of the hair (about 0.3-0.5 μm) is composed of overlapping squamous cells, and the cortex is composed of elongated cortical cells of about 100 μm in length. Sponge needles are natural materials used as carriers in transdermal drug delivery systems. Needles are typically siliceous or calcareous, providing structural support to most sponges. They are needle-like structures with tips growing from two opposite sites. The spongiform bodies have high adaptability and outstanding skin absorption enhancement capability for local application, and enhance the skin absorption of a series of low-permeability medicines in vitro and in vivo, so that the spongiform bodies become a novel infiltration promotion method with good application prospect. In order to overcome the barrier of the stratum corneum, the microneedle is a direct physical method, the application area of the microneedle patch is small, the metal microneedle can form a microchannel, but the needle body is thicker (0.2 mm), the pain feeling is strong in operation, anesthetic needs to be matched, the blood vessel is easy to puncture to cause bleeding and wound infection, the postoperative care is complex, and the chemical permeation enhancer such as azone can improve the permeation efficiency, but has limited permeation promoting effect on macromolecular components and possibly causes skin irritation. Therefore, the development of a noninvasive, efficient and safe technology for promoting penetration of hair growth ingredients becomes a problem to be solved urgently in the industry. The sponge microneedle (HS) is used as a novel silicon microneedle, has the advantages of slender needle body (1 g of 99% purity sponge microneedle contains 500-600 ten thousand needle bodies), no anesthesia requirement, no bleeding, low infection risk and the like, can be used alone or in combination with an active ingredient to overcome skin barriers, can generate a large number of novel lasting microchannels (about 800 micropores per square millimeter for more than 48 hours) to enter in a minimally invasive manner, and enhances the absorption of skin to active molecules. Sta