Hair growing composition for enhancing hair follicle microcirculation by using cacumen biotae volatile oil and kaoliang spirit alcohol extract

Abstract

The invention discloses a hair growth composition for enhancing hair follicle microcirculation by using cacumen biotae volatile oil and a kaoliang spirit alcohol extract and a preparation method thereof, and belongs to the technical field of hair growth and care products, the hair growth composition comprises the following components in percentage by mass: a hair follicle microcirculation activation component: 0.01-0.05 wt% of cacumen biotae volatile oil and 0.1-5.0 wt% of kaoliang spirit alcohol extract; an extracellular matrix strengthening and intercellular communication promoting component: 0.001 to 0.05 wt% of acetyl tetrapeptide-3; 0.1 to 2.0 wt% of an angelica polysaccharide extract; 0.1 to 1.0 wt% of sodium hyaluronate; and 0.05-2.0 wt% of carbenoxolone acid, which is used for up-regulating the expression of Connexin43 (Cx43) protein in hair follicle outer root sheath cells. The composition aims at solving the technical problems that an existing hair growth product only improves hair follicle microcirculation but cannot effectively wake up the activity of hair follicle stem cells, and continuous hair growth is difficult to achieve.

Description

Technical Field

[0001] This invention relates to the field of hair growth and hair care products, specifically to a hair growth composition that utilizes the volatile oil of Platycladus orientalis leaves and the alcohol extract of sorghum liquor to enhance the microcirculation of hair follicles, and its preparation method. Background Technology

[0002] Hair follicle microcirculation refers to the process by which the capillaries in the scalp deliver oxygen and nutrients to the hair follicles. Healthy hair follicle microcirculation is crucial for maintaining normal hair follicle function and hair growth. When hair follicle microcirculation is impaired, the hair follicles cannot receive sufficient nutrients, which may lead to problems such as hair loss and thinning hair.

[0003] While some existing products contain extracts of arborvitae leaves or sorghum liquor, most of these products only have a single effect of improving microcirculation or anti-oxidation, and cannot effectively awaken the activity of hair follicle stem cells, making it difficult to achieve sustained hair growth. Therefore, their effect on promoting hair follicle regeneration is limited.

[0004] Many existing hair growth products focus on "hair growing," but neglect "whether the hair is strong." Many patients experience a temporary increase in hair growth after using the medication, only to lose it again upon discontinuation. The root cause lies in the failure to rebuild the ECM structure around the hair follicle, resulting in poor anchoring ability.

[0005] Most hair regrowth products currently focus only on activating individual hair follicles (such as minoxidil-induced vasodilation), but neglect the biological mechanism by which hair follicles synchronize signals through gap junctions (Cx43). When Cx43 expression decreases, even if individual hair follicles are activated, a "group anagen phase restart" cannot be achieved, resulting in short-lived therapeutic effects.

[0006] The core pathological mechanisms of hair loss include hair follicle microcirculation disorders, decreased activity of hair follicle mesenchymal stem cells, and cell cycle arrest. While existing treatments such as minoxidil and finasteride are effective to some extent, their mechanisms of action do not specifically target hair follicle microcirculation disorders, and they suffer from limited efficacy and numerous side effects. Summary of the Invention

[0007] In order to overcome the shortcomings of the prior art, one of the objectives of the present invention is to provide a hair growth composition that enhances the microcirculation of hair follicles by using volatile oil from arborvitae leaves and alcohol extract from sorghum liquor. This composition aims to solve the technical problem that existing hair growth products only improve the microcirculation of hair follicles but cannot effectively awaken the activity of hair follicle stem cells, making it difficult to achieve continuous hair growth, so as to synergistically promote hair follicle regeneration.

[0008] The second objective of this invention is to provide a method for preparing a hair growth composition that enhances hair follicle microcirculation by using volatile oil from Platycladus orientalis leaves and alcohol extract from sorghum liquor. This method ensures the efficient coexistence and synergistic delivery of multiple active ingredients with significant polarity differences in the same formulation, overcoming the inherent limitations of single microemulsion systems in terms of stability, sustained release, and targeting.

[0009] The third objective of this invention is to provide an application of a hair growth composition that utilizes the volatile oil of Platycladus orientalis leaves and the alcohol extract of sorghum liquor to enhance the microcirculation of hair follicles.

[0010] One of the objectives of this invention is achieved through the following technical solution: A hair growth composition that utilizes volatile oil from Platycladus orientalis leaves and alcohol extract from sorghum liquor to enhance microcirculation in hair follicles, comprising the following components by weight percentage: Hair follicle microcirculation activating components: 0.01-0.05 wt% arborvitae leaf volatile oil, 0.1-5.0 wt% sorghum liquor extract; Extracellular matrix strengthening and cell-to-cell communication enhancement components: Acetyl tetrapeptide-3: 0.001–0.05 wt%, used to stimulate dermal papillary cells to synthesize type III collagen and laminin; Angelica polysaccharide extract: 0.1–2.0 wt%, used to synergistically increase hydroxyproline content; Sodium hyaluronate: 0.1–1.0 wt%, as a moisturizing and penetration enhancer; Glycyrrhetinic acid: 0.05–2.0 wt%, used to upregulate the expression of Connexin43 (Cx43) protein in outer root sheath cells of hair follicles; Wnt pathway activation components: Salidroside (0.06–1.2 wt%) can activate the Wnt / β-catenin pathway, promote DP cell proliferation, and induce hair follicles to enter the growth phase. Lithium salts (such as lithium chloride or lithium orotate): 0.05–1.0 wt%, as GSK-3β inhibitors to activate the Wnt / β-catenin signaling pathway; Hordenine 0.01–0.5% has been shown to promote hair growth through the Wnt pathway; Hair follicle stem cell regeneration component: R-spondin1 mimic peptide 0.001-0.2wt%, as a small molecule LGR5 agonist, specifically activates LGR5+ hair follicle stem cells; Cell cycle restart components: Nicotinamide mononucleotide 0.01-1.0 wt%, caffeine 0.1-2.0%, as glycogen phosphorylase activator, activate the "Corley cycle" in hair follicles and enhance energy metabolism.

[0011] Furthermore, the volatile oil from the arborvitae leaves contains at least 10% α-thujone and at least 5% fenestrantone, and is obtained through an ultrasonic-assisted extraction process.

[0012] Furthermore, the composition exists in the form of a water-alcohol-oil three-phase microemulsion, wherein: Oil phase: contains a portion of volatile oil from arborvitae leaves, as well as hydrophobic or lipophilic components, including hordenine; Aqueous phase: A mixed solution containing water-soluble components, including PLGA nanoparticles dispersed with sorghum liquor extract, the nanoparticles having an average particle size of 10–200 nm for sustained release and targeted delivery of the active ingredient; transfersomes loaded with acetyl tetrapeptide-3 and R-spondin1 mimetic peptides; nanostructured lipid carriers (NLCs) loaded with another portion of Platycladus orientalis leaf volatile oil; transfersomes loaded with glycine palmitate; cationic liposomes loaded with nicotinamide mononucleotide, the liposomes being composed of DOTAP, DOPE, and cholesterol; PLGA nanoparticles loaded with rhodioloside; Angelica sinensis polysaccharide extract; sodium hyaluronate; and lithium salt. Alcohol phase: An ethanol solution containing caffeine, used as a solubilizing and soluble phase to promote the interfacial fusion of the oil phase and the aqueous phase; First, the alcohol phase is slowly added to the oil phase under stirring, and then slowly added to the aqueous phase. The three phases are mixed in proportion, and a transparent, homogeneous, and thermodynamically stable microemulsion system is formed through an ultrasonic-assisted emulsification process.

[0013] Furthermore, the preparation of the PLGA nanoparticles loaded with sorghum liquor extract includes the following steps: S1. Extraction and concentration: The active ingredients in sorghum liquor were extracted by reflux using 75% ethanol and concentrated at 60°C to a relative density of 1.05–1.10 to obtain a sorghum liquor alcohol extract solution. S2. Preparation of nanoparticle precursor solution: Prepare an organic phase solution containing polylactic acid-glycolic acid copolymer (PLGA); prepare an aqueous phase solution containing a surfactant (such as polysorbate 80); S3. Mixing and nanoparticle formation in the microfluidic chip: The sorghum liquor extract solution, the organic phase solution containing polylactic acid-glycolic acid copolymer, and the aqueous phase solution containing surfactant are introduced into different microchannels of the microfluidic chip; in the microfluidic chip, by precisely controlling the flow rate and mixing conditions of each solution, the sorghum liquor extract solution is mixed with the organic phase solution containing polylactic acid-glycolic acid copolymer to form an oil-in-water (O / W) emulsion; S4. The oil-in-water (O / W) emulsion is evaporated by solvent to form polylactic acid-glycolic acid copolymer nanoparticles, and the active ingredients in the sorghum liquor extract are uniformly encapsulated in the polylactic acid-glycolic acid copolymer nanoparticles. S5. Post-processing: The formed nanoparticle solution is centrifuged to remove excess surfactants and unencapsulated active ingredients; the nanoparticles are washed multiple times with deionized water to ensure the nanoparticle surface is clean; the final nanoparticles are characterized by TEM and DLS to ensure uniform size distribution and uniform dispersion of active ingredients. The sorghum liquor extract is extracted by reflux extraction with 75% ethanol, concentrated to a relative density of 1.05–1.10, and treated with microfluidics to improve its stability. The microfluidics treatment includes encapsulating the active ingredients in the sorghum liquor extract in nanoparticles.

[0014] Furthermore, the preparation of the transferrin loaded with acetyl tetrapeptide-3 and R-spondin1 mimic peptide includes the following steps: weighing 80 mg of lecithin, 20 mg of cholesterol, and 10 mg of sodium cholate, dissolving them in chloroform, and rotary evaporating to form a uniform lipid film; Add PBS buffer at pH 7.4 containing 2 mg acetyl tetrapeptide-3 and 2 mg R-spondin1 mimetic peptide, and hydrate for 1 hour; The solution was ultrasonically treated with 150W for 3 minutes to obtain a transparent nano-dispersion, which was then sterilized by passing it through a 0.22μm filter membrane and stored at 4℃.

[0015] Furthermore, the preparation of the nanostructured lipid carrier (NLC) loaded with another portion of Platycladus orientalis leaf volatile oil includes the following steps: weighing 60 mg of stearic acid (solid lipid), 40 mg of squalene (liquid oil), and another portion of 20 mg of Platycladus orientalis leaf volatile oil, and heating to 75°C to melt. Separately, prepare an aqueous phase: dissolve 20 mg of polysorbate 80 in 10 mL of purified water and heat to 75°C; Slowly add the oil phase to the aqueous phase and stir at high speed for 5 minutes at 10,000 rpm to pre-emulsify; 1000 bar, high-pressure homogenization, 3 cycles; Cool to room temperature to obtain a white emulsion.

[0016] Furthermore, the hair growth composition is in the form of a scalp serum, spray, gel, or soluble microneedle patch.

[0017] The second objective of this invention is achieved by the following technical solution: A method for manufacturing a hair growth composition that enhances hair follicle microcirculation using volatile oil from arborvitae leaves and sorghum liquor extract includes the following steps: S1. Prepare the transferor loaded with acetyl tetrapeptide-3 and R-spondin1 mimic peptide, the transferor loaded with glycine palm, the nanostructured lipid carrier loaded with another portion of Platycladus orientalis leaf volatile oil, and the aqueous dispersion of the cationic liposome loaded with nicotinamide mononucleotide. S2. Mix the above nanoparticle dispersion, add the PLGA nanoparticles loaded with rhodioloside, the PLGA nanoparticles loaded with sorghum wine extract, and lithium salt to form a composite aqueous phase. S3. Dissolve a portion of the volatile oil from the arborvitae leaves and hordenine in the oil phase; S4. Dissolve caffeine in ethanol to form the alcohol phase; S5. First, slowly add the alcohol phase to the oil phase under stirring, and then slowly add it to the aqueous phase. Mix the components in proportion to form a transparent microemulsion. Through an ultrasonic-assisted emulsification process, a stable three-phase microemulsion is formed to obtain the hair growth composition that enhances hair follicle microcirculation using arborvitae leaf volatile oil and sorghum liquor alcohol extract.

[0018] A method for preparing a soluble microneedle patch for promoting hair growth includes the following steps: S1. Take 10 mL of the hair growth composition that enhances hair follicle microcirculation by using volatile oil from arborvitae leaves and sorghum liquor extract, mix it with 50 mg of carboxymethyl chitosan, 30 mg of sodium alginate and 10 mg of glycerin, add water to 1 mL, and stir evenly. S2. Inject into the microneedle mold and vacuum dry at 40℃ for 12 hours; S3. After demolding, a microneedle patch is obtained, with needles 300–600 μm in length, used to deliver drugs to the hair follicle protuberance area. The needle is transparent and completely dissolves in the skin moisture within 10 minutes at room temperature.

[0019] The third objective of this invention is to provide a hair growth composition that utilizes the volatile oil of Platycladus orientalis leaves and the alcohol extract of sorghum liquor to enhance the microcirculation of hair follicles in the preparation of products that promote hair follicle regeneration, improve hair density, or delay hair follicle aging. The product is a topical preparation, preferably for local application to the scalp.

[0020] Compared with the prior art, the beneficial effects of the present invention are as follows: (1) The present invention provides a hair growth composition that enhances hair follicle microcirculation by using volatile oil from Platycladus orientalis leaves and alcohol extract from sorghum liquor. The volatile oil from Platycladus orientalis leaves and alcohol extract from sorghum liquor improve microcirculation, providing a nutrient and signal delivery environment for stem cells, and synergistically enhance the effects. The Platycladus orientalis leaf extract contains quercetin, kaempferol, thujone, and polysaccharides, which inhibit 5α-reductase, control oil, reduce inflammation, and promote hair follicle cell proliferation. The alcohol extract from sorghum liquor contains ethyl acetate, ethanol, aldehydes, ketones, and phenols, which dilate blood vessels, promote hair follicle microcirculation, resist Malassezia, and promote transdermal absorption. Nicotinamide mononucleotide enhances HDAC1 / 2 activity, inhibits p53 acetylation and p21 expression, relieves cell cycle arrest, and simultaneously increases NAD+ levels. It activates SIRT1, inhibits p53 acetylation, delays hair follicle stem cell aging, and counteracts the depletion of hair follicle stem cells (HFSC) caused by excessive IGF-1. It can significantly reduce aging markers, alleviate premature aging phenotypes of hair follicles, and thus restore the hair follicle stem cell pool. The combined use of Platycladus orientalis leaf volatile oil and nicotinamide mononucleotide can significantly reduce the expression level of p16 in hair follicle stem cells. Its effect is far superior to that of any single component. Platycladus orientalis leaf increases NAD+ levels by activating the AMPK pathway and forms a 'substrate-pathway' synergy with nicotinamide mononucleotide to jointly activate SIRT1, thereby inhibiting p16 gene transcription, delaying stem cell aging, and providing a new strategy for treating age-related hair loss. It can also strengthen and promote intercellular communication components through the extracellular matrix, making hair grow stronger and hair grow synchronously in the hair removal area. Combined with the activation of the Wnt / β-catenin pathway, it can initiate hair follicle regeneration. The hair follicle stem cell regeneration component specifically activates stem cells and initiates self-renewal. The activated stem cells can differentiate into hair matrix cells. The hair matrix cells proliferate rapidly and form new hair shafts. It specifically awakens LGR5+ hair follicle stem cells and initiates the transition of hair follicles from the resting phase to the growth phase. The cell cycle restart component acts on hair follicle matrix cells and hair papilla cells, enhances energy metabolism, restarts the cell cycle of dormant hair follicles, and supports hair shaft growth.

[0021] (2) The present invention provides a method for preparing a hair growth composition that enhances hair follicle microcirculation by using volatile oil of Platycladus orientalis leaves and alcohol extract of sorghum liquor, S1, respectively preparing the transferrin loaded with acetyl tetrapeptide-3 and R-spondin1 mimic peptide, the transferrin loaded with glycine palmitate, the nanostructured lipid carrier loaded with another part of volatile oil of Platycladus orientalis leaves, and the aqueous dispersion of the cationic liposome loaded with nicotinamide mononucleotide; S2. Mix the above nanoparticle dispersion, and add the PLGA nanoparticles loaded with rhodioloside and the PLGA nanoparticles loaded with sorghum wine extract. The nanoparticles are small in size and have high transdermal absorption efficiency when applied directly externally. The transferor loaded with acetyl tetrapeptide-3 and R-spondin1 mimic peptides prevents the degradation of acetyl tetrapeptide-3 and R-spondin1 mimic peptides by proteases; the cationic liposome loaded with nicotinamide mononucleotide prevents the nicotinamide mononucleotide from being released directionally in the weakly acidic environment of hair follicles (pH~5.5) and hydrolyzed; the PLGA nanoparticles loaded with rhodioloside and the PLGA nanoparticles loaded with sorghum wine extract are suitable for small molecules, moderately polar compounds, and soluble in ethanol / ethyl acetate; the nanostructured lipid carrier loaded with another portion of the volatile oil of Platycladus orientalis leaves prevents the volatile oil of Platycladus orientalis leaves from oxidizing and photodegrading; the transferor loaded with glycine brown significantly prolongs its half-life due to the weak water solubility and easy oxidation of glycine, thus improving the stability of the active ingredients. By constructing a water-alcohol-oil three-phase microemulsion system, we have for the first time achieved the efficient coexistence and synergistic delivery of multiple active ingredients with significant polarity differences, such as volatile oil from Platycladus orientalis leaves, alcohol extract from sorghum liquor, peptides, and small molecule agonists, in the same formulation. This not only solves the problems of easy stratification, poor stability, and insufficient penetration in traditional hair growth products, but also significantly enhances the targeted enrichment ability of active ingredients in the hair follicle ridge area through the microemulsion-nanoparticle composite structure, overcoming the inherent limitations of single microemulsion systems in terms of stability, sustained release, and targeting.

[0022] (3) The present invention provides a method for preparing a soluble microneedle patch for promoting hair growth. Traditional cleansers, sprays, and serums can only act on the epidermis and cannot effectively accumulate in the bulge region, where hair follicle stem cells (LGR5+ cells) are primarily located. Microneedles, 300–600 μm in length, penetrate the stratum corneum, reaching the hair follicle neck to the bulge region (approximately 300–500 μm deep), enabling long-term targeted delivery of active ingredients. Carboxymethyl chitosan (CMC) has good biocompatibility and possesses moisturizing, antibacterial, and wound-healing properties; sodium alginate swells upon contact with water, rapidly releasing the drug and forming a gel-like sustained-release layer. Detailed Implementation

[0023] The present invention will now be further described in conjunction with specific embodiments. It should be noted that, without conflict, the embodiments or technical features described below can be arbitrarily combined to form new embodiments.

[0024] Hair follicle microcirculation disorder: Definition: Hair follicle microcirculation disorder refers to the damage to the microvascular network around the hair follicle, resulting in the hair follicle not receiving enough oxygen and nutrients.

[0025] Impact: This barrier directly affects the health of hair follicles, leading to follicle atrophy and hair loss. Improving hair follicle microcirculation is an important direction for treating hair loss.

[0026] Decreased activity of hair follicle mesenchymal stem cells (HF-MSCs): Definition: Hair follicle mesenchymal stem cells are key cells for hair follicle regeneration, and a decrease in their activity will lead to a weakening of the hair follicle's regenerative capacity.

[0027] Impact: Decreased activity of these stem cells reduces the regenerative capacity of hair follicles, causing them to gradually shrink and eventually leading to hair loss.

[0028] Cell cycle arrest: Definition: Cell cycle arrest refers to a decrease in the proliferative capacity of hair follicle cells, with the cell cycle stopping at a certain stage and unable to enter the growth phase normally.

[0029] Impact: This blockage causes hair follicles to remain in the resting phase and unable to enter the growth phase, thus leading to hair loss.

[0030] Insulin-like growth factor-1 (IGF-1) stimulates VEGF expression and promotes angiogenesis, exhibiting a dual effect: moderate amounts promote angiogenesis, while excessive amounts lead to age-related decline. Example 1

[0031] This embodiment provides a hair growth composition that enhances hair follicle microcirculation using volatile oil from Platycladus orientalis leaves and sorghum liquor extract, comprising the following components by weight percentage: Hair follicle microcirculation activating components: 0.03wt% arborvitae leaf volatile oil, 0.1wt% sorghum liquor alcohol extract; Extracellular matrix strengthening and cell-to-cell communication enhancement components: Acetyl tetrapeptide-3: 0.01 wt%, used to stimulate dermal papillary cells to synthesize type III collagen and laminin; Angelica polysaccharide extract: 0.1wt%, used to synergistically increase hydroxyproline content; Sodium hyaluronate: 0.5 wt%, as a moisturizing and penetration enhancer; Glycyrrhetinic acid: 0.1 wt%, used to upregulate the expression of Connexin43 (Cx43) protein in outer root sheath cells of hair follicles; Wnt pathway activation components: Salidroside (0.06 wt%) can activate the Wnt / β-catenin pathway, promote DP cell proliferation, and induce hair follicles to enter the growth phase. Lithium salts (such as lithium chloride or lithium orotate): 0.05 wt%, as a GSK-3β inhibitor to activate the Wnt / β-catenin signaling pathway; Hordenine 0.01% has been shown to promote hair growth through the Wnt pathway; Hair follicle stem cell regeneration component: R-spondin1 mimic peptide 0.001wt%, as a small molecule LGR5 agonist, specifically activates LGR5+ hair follicle stem cells; Cell cycle restart components: nicotinamide mononucleotide 0.01wt%, caffeine 2.0%, as glycogen phosphorylase activator, activate the "Corley cycle" in hair follicles and enhance energy metabolism.

[0032] In this embodiment, the α-thujone content in the volatile oil of Platycladus orientalis leaves is not less than 10%, and the anethole content is not less than 5%, and it is obtained by ultrasound-assisted extraction process.

[0033] In this embodiment, the composition exists in the form of a water-alcohol-oil three-phase microemulsion, wherein: Oil phase: contains a portion of volatile oil from arborvitae leaves, as well as hydrophobic or lipophilic components, including hordenine; Aqueous phase: A mixed solution containing water-soluble components, including PLGA nanoparticles dispersed with sorghum liquor extract, the nanoparticles having an average particle size of 10–200 nm, for sustained release and targeted delivery of active ingredients; transfersomes loaded with acetyl tetrapeptide-3 and R-spondin1 mimetic peptides; nanostructured lipid carriers (NLCs) loaded with another portion of Platycladus orientalis leaf volatile oil; transfersomes loaded with glycine palmitate; cationic liposomes loaded with nicotinamide mononucleotide, the liposomes being composed of DOTAP, DOPE, and cholesterol; PLGA nanoparticles loaded with rhodioloside; Angelica sinensis polysaccharide extract; sodium hyaluronate; and lithium salt. Alcohol phase: An ethanol solution containing caffeine, used as a solubilizing and soluble phase to promote the interfacial fusion of the oil phase and the aqueous phase; First, the alcohol phase is slowly added to the oil phase under stirring, and then slowly added to the aqueous phase. The three phases are mixed in proportion, and a transparent, homogeneous, and thermodynamically stable microemulsion system is formed through an ultrasonic-assisted emulsification process.

[0034] Advantages of nanoparticle encapsulation Nanoparticle encapsulation can effectively solve the above problems, with the following specific advantages: Enhance bioavailability Improved solubility: Nanoparticles can significantly improve the solubility of active ingredients, allowing them to be more uniformly dispersed in formulations, thereby improving their bioavailability.

[0035] Enhanced permeability: The small size of nanoparticles allows them to penetrate the stratum corneum around the hair follicle more effectively, delivering active ingredients directly into the hair follicle and improving their effectiveness within it.

[0036] Sustained release effect Sustained release: Nanoparticles can achieve sustained release of active ingredients, allowing them to continue to exert their effects in the hair follicles, prolonging their duration of action and improving treatment efficacy.

[0037] This embodiment provides a method for preparing a hair growth composition that enhances hair follicle microcirculation using volatile oil from Platycladus orientalis leaves and sorghum liquor extract, comprising the following steps: S1. Prepare transferrin loaded with acetyl tetrapeptide-3 and R-spondin1 mimic peptide, transferrin loaded with glycine palm, nanostructured lipid carrier loaded with another part of arborvitae leaf volatile oil, and aqueous dispersion of cationic liposome loaded with nicotinamide mononucleotide. S2. Mix the above nanoparticle dispersion, add PLGA nanoparticles loaded with rhodioloside, PLGA nanoparticles loaded with sorghum wine extract, lithium salt, sodium hyaluronate, and form a composite aqueous phase. S3. Dissolve a portion of the volatile oil from the arborvitae leaves and hordenine in the oil phase; S4. Dissolve caffeine in ethanol to form the alcohol phase; S5. First, the alcohol phase is slowly added to the oil phase under stirring, and then slowly added to the aqueous phase. The components are mixed in proportion to form a transparent microemulsion. Through an ultrasonic-assisted emulsification process, a stable three-phase microemulsion is formed, resulting in a hair growth composition that enhances hair follicle microcirculation using arborvitae leaf volatile oil and sorghum liquor alcohol extract.

[0038] In this embodiment, the preparation of PLGA nanoparticles loaded with sorghum liquor extract includes the following steps: S1. Extraction and concentration: The active ingredients in sorghum liquor were extracted by reflux using 75% ethanol and concentrated at 60°C to a relative density of 1.05–1.10 to obtain a sorghum liquor alcohol extract solution. S2. Preparation of nanoparticle precursor solution: Prepare an organic phase solution containing polylactic acid-glycolic acid copolymer (PLGA); prepare an aqueous phase solution containing a surfactant (such as polysorbate 80); S3. Mixing and nanoparticle formation in microfluidic chip: A sorghum liquor extract solution, an organic phase solution containing polylactic acid-glycolic acid copolymer, and an aqueous phase solution containing surfactant are introduced into different microchannels of the microfluidic chip. In the microfluidic chip, by precisely controlling the flow rate and mixing conditions of each solution, the sorghum liquor extract solution is mixed with the organic phase solution containing polylactic acid-glycolic acid copolymer to form an oil-in-water (O / W) emulsion. S4. The oil-in-water (O / W) emulsion is evaporated by solvent to form polylactic acid-glycolic acid copolymer nanoparticles. The active ingredients in the sorghum liquor extract are uniformly encapsulated in the polylactic acid-glycolic acid copolymer nanoparticles. S5. Post-processing: The formed nanoparticle solution is centrifuged to remove excess surfactants and unencapsulated active ingredients; the nanoparticles are washed multiple times with deionized water to ensure the nanoparticle surface is clean; the final nanoparticles are characterized by TEM and DLS to ensure uniform size distribution and uniform dispersion of active ingredients. The sorghum liquor extract is extracted by reflux with 75% ethanol, concentrated to a relative density of 1.05–1.10, and then treated with microfluidics to improve its stability. The microfluidics treatment includes encapsulating the active ingredients in the sorghum liquor extract in nanoparticles.

[0039] In this embodiment, the preparation of the transferrin loaded with acetyl tetrapeptide-3 and R-spondin1 mimic peptide includes the following steps: weigh 80 mg of lecithin, 20 mg of cholesterol and 10 mg of sodium cholate and dissolve them in chloroform, then rotary evaporate to form a uniform lipid film. Add PBS buffer at pH 7.4 containing 2 mg acetyl tetrapeptide-3 and 2 mg R-spondin1 mimetic peptide, and hydrate for 1 hour; The solution was ultrasonically treated with 150W for 3 minutes to obtain a transparent nano-dispersion, which was then sterilized by passing it through a 0.22μm filter membrane and stored at 4℃.

[0040] In this embodiment, the preparation of the nanostructured lipid carrier (NLC) loaded with another portion of Platycladus orientalis leaf volatile oil includes the following steps: weigh 60 mg of stearic acid (solid lipid), 40 mg of squalene (liquid oil), and another portion of 20 mg of Platycladus orientalis leaf volatile oil, and heat to 75°C to melt. Separately, prepare an aqueous phase: dissolve 20 mg of polysorbate 80 in 10 mL of purified water and heat to 75°C; Slowly add the oil phase to the aqueous phase and stir at high speed for 5 minutes at 10,000 rpm to pre-emulsify; 1000 bar, high-pressure homogenization, 3 cycles; Cool to room temperature to obtain a white emulsion. Example 2

[0041] This embodiment provides a hair growth composition that enhances hair follicle microcirculation using volatile oil from Platycladus orientalis leaves and sorghum liquor extract, comprising the following components by weight percentage: Hair follicle microcirculation activating components: 0.01 wt% arborvitae leaf volatile oil, 3.0 wt% sorghum liquor alcohol extract; Extracellular matrix strengthening and cell-to-cell communication enhancement components: Acetyl tetrapeptide-3: 0.001 wt%, used to stimulate dermal papillary cells to synthesize type III collagen and laminin; Angelica polysaccharide extract: 0.8wt%, used to synergistically increase hydroxyproline content; Sodium hyaluronate: 0.1 wt%, as a moisturizing and penetration enhancer; Glycyrrhetinic acid: 0.05 wt%, used to upregulate the expression of Connexin43 (Cx43) protein in outer root sheath cells of hair follicles; Wnt pathway activation components: Salidroside (0.5 wt%) can activate the Wnt / β-catenin pathway, promote DP cell proliferation, and induce hair follicles to enter the growth phase. Lithium salts (such as lithium chloride or lithium orotate): 0.5 wt%, as GSK-3β inhibitors to activate the Wnt / β-catenin signaling pathway; Hordenine 0.09% has been shown to promote hair growth through the Wnt pathway; Hair follicle stem cell regeneration component: R-spondin1 mimic peptide 0.08wt%, as a small molecule LGR5 agonist, specifically activates LGR5+ hair follicle stem cells; Cell cycle restart components: 0.5 wt% nicotinamide mononucleotide and 0.1% caffeine, which act as glycogen phosphorylase activators to activate the "Corley cycle" within hair follicles and enhance energy metabolism. Example 3

[0042] This embodiment provides a hair growth composition that enhances hair follicle microcirculation using volatile oil from Platycladus orientalis leaves and sorghum liquor extract, comprising the following components by weight percentage: Hair follicle microcirculation activating components: 0.05wt% arborvitae leaf volatile oil, 5.0wt% sorghum liquor alcohol extract; Extracellular matrix strengthening and cell-to-cell communication enhancement components: Acetyl tetrapeptide-3: 0.05 wt%, used to stimulate dermal papillary cells to synthesize type III collagen and laminin; Angelica polysaccharide extract: 2.0 wt%, used to synergistically increase hydroxyproline content; Sodium hyaluronate: 1.0 wt%, as a moisturizing and penetration enhancer; Glycyrrhetinic acid: 2.0 wt%, used to upregulate the expression of Connexin43 (Cx43) protein in outer root sheath cells of hair follicles; Wnt pathway activation components: Salidroside (1.2 wt%) can activate the Wnt / β-catenin pathway, promote DP cell proliferation, and induce hair follicles to enter the growth phase. 1.0 wt% lithium salt (such as lithium chloride or lithium orotate) was used as a GSK-3β inhibitor to activate the Wnt / β-catenin signaling pathway; Hordenine 0.5% has been shown to promote hair growth through the Wnt pathway; Hair follicle stem cell regeneration component: R-spondin1 mimic peptide 0.001-0.2wt%, as a small molecule LGR5 agonist, specifically activates LGR5+ hair follicle stem cells; Cell cycle restart components: nicotinamide mononucleotide 1.0 wt% and caffeine 0.8%, which act as glycogen phosphorylase activators to activate the "Corley cycle" within hair follicles and enhance energy metabolism. Example 4

[0043] Soluble microneedle patches Includes the following steps: S1. Take 10 mL of the hair growth composition that enhances hair follicle microcirculation by using volatile oil from arborvitae leaves and sorghum liquor extract, mix it with 50 mg of carboxymethyl chitosan, 30 mg of sodium alginate and 10 mg of glycerin, add water to 1 mL, and stir well. S2. Inject into the microneedle mold and vacuum dry at 40℃ for 12 hours; S3. After demolding, a microneedle patch is obtained, with needles 300–600 μm in length, used to deliver drugs to the hair follicle protuberance area. The needle is transparent and completely dissolves in the skin moisture within 10 minutes at room temperature.

[0044] Experimental Example The effect of the composition of Example 1 of this invention on extracellular matrix reconstruction and hair anchoring force Using a C57BL / 6 mouse dorsal hair removal model, the animals were randomly divided into five groups (n=6), and the following formula was applied topically to each group: Control group: Contains only volatile oil from arborvitae leaves (0.03 wt%) and sorghum liquor extract (0.1 wt%). Group 1: Comparative example + Acetyl tetrapeptide-3 (0.01wt%); Group 2: Comparative example + Angelica sinensis polysaccharide extract (0.1wt%); Group 3: Comparative Example + Acetyl Tetrapeptide-3 (0.01wt%) + Angelica Polysaccharide Extract (0.1wt%); Group 4: Example 3 + Glyceric acid (0.1wt%).

[0045] Testing indicators: 1. Type III collagen (COL3A1) expression (WB) 2. Laminin-5 secretion (ELISA) 3. Hydroxyproline content (colorimetric method) 4. Connexin43 (Cx43) protein expression (WB) 5. Intercellular calcium wave conduction velocity (Fluo-4AM imaging) 6. Hair density (roots / cm²) 7. Hair diameter (μm) 8. Pulling force of a single hair (mN, using a precision force gauge) After 21 days of continuous administration, hair density, diameter, and pull-out force of a single hair were measured. Skin tissue was also taken for analysis of the expression of type III collagen, hydroxyproline, and Connexin 43 proteins. The results are shown in Tables 1 and 2.

[0046] Table 1 Group Type III collagen content Hydroxyproline content Connexin 43 protein content control group 1.3 times 1.2 times 1.1 times Group 1 1.8 times 1.5 times 1.2 times Group 2 1.6 times 1.7 times 1.1 times Group 3 2.5 times 2.6 times 1.3 times Group 4 2.7 times 2.8 times 2.4 times The experimental results showed that groups 1 and 2 could only produce limited improvements in collagen or hydroxyproline, while group 3 significantly enhanced ECM synthesis, and acetyl tetrapeptide-3 and Angelica polysaccharide extract showed a synergistic effect; group 4 further upregulated Cx43 expression and significantly increased intercellular calcium wave conduction speed on the basis of ECM, which for the first time proved that ECM enhancement and intercellular communication synchronization are the key mechanisms to prevent hair loss and cessation of hair growth, and this synergistic effect is significantly better than the traditional approach that only improves microcirculation.

[0047] Table 2 Group Hair density (roots / cm²) Hair diameter (μm) Pull-out force (mN) Percentage of hair follicles in the growth phase (%) control group 110±14 42±5 8.5±1.2 45±6 Group 1 132±16 46±4 9.8±1.1 52±5 Group 2 128±15 45±5 9.5±1.3 50±7 Group 3 156±18 50±6 12.3±1.5 65±8 Group 4 162±20 52±5 14.1±1.6 72±9 Experimental results showed that the hair density in group 4 reached 162 ± 20 hairs / cm², and the proportion of hair follicles in the growth phase reached 72%, indicating that the present invention can not only promote hair growth, but also enhance the stability of the hair follicle microenvironment, achieving a "long and strong" hair growth effect.

[0048] The above embodiments are merely preferred embodiments of the present invention and should not be construed as limiting the scope of protection of the present invention. Any non-substantial changes and substitutions made by those skilled in the art based on the present invention shall fall within the scope of protection claimed by the present invention.

Claims

1. A hair growth composition for enhancing microcirculation of hair follicles by using volatile oil of Platycladus orientalis and alcohol extract of sorghum liquor, characterized in that, By mass percentage, comprising the following components: Hair follicle microcirculation activating components: 0.01-0.05wt% of cypress leaf volatile oil, 0.1-5.0wt% of sorghum wine alcohol extract; Extracellular matrix strengthening and promoting intercellular communication components: Acetyl tetrapeptide-3: 0.001–0.05wt%, for stimulating dermal papilla cells to synthesize type III collagen and laminin; Angelica polysaccharide extract: 0.1–2.0wt%, for synergistically increasing hydroxyproline content; Sodium hyaluronate: 0.1–1.0wt%, as a moisturizing and penetration enhancer; Carbenoxolone: 0.05–2.0wt%, for up-regulating the expression of Connexin43 (Cx43) protein in the outer root sheath cells of hair follicles; Wnt pathway activating components: Salidroside: 0.06–1.2wt%, which can activate the Wnt / β-catenin pathway, promote DP cell proliferation, and induce hair follicles to enter the growth phase; Lithium salt: 0.05–1.0wt%, as a GSK-3β inhibitor to activate the Wnt / β-catenin signaling pathway; Hordenine 0.01–0.5%, which has been proven to promote hair growth through the Wnt pathway; Hair follicle stem cell regeneration components: R-spondin1 mimetic peptide 0.001-0.2wt%, as an LGR5 agonist small molecule, specifically activating LGR5+ hair follicle stem cells; Cell cycle restart components: nicotinamide mononucleotide 0.01-1.0wt%, caffeine 0.1–2.0%, as a glycogen phosphorylase activator, activating the Korner cycle in hair follicles and improving energy metabolism.

2. The hair growth composition for enhancing microcirculation of hair follicle by using volatile oil of biota orientalis and alcohol extract of sorghum liquor according to claim 1, wherein the volatile oil of biota orientalis and the alcohol extract of sorghum liquor are mixed in a ratio of 1: 1 to 1:

10. The composition exists in the form of a water-alcohol-oil three-phase microemulsion, wherein: The oil phase contains a portion of cypress leaf volatile oil and hydrophobic or fat-soluble ingredients, including hordenine; The water phase contains a mixed solution of water-soluble ingredients, including PLGA nanoparticles loaded with sorghum wine alcohol extract, with an average particle size of 10–200nm, for achieving slow release and targeted delivery of active ingredients; transferrin loaded with acetyl tetrapeptide-3 and R-spondin1 mimetic peptide; nanostructured lipid carriers loaded with another portion of cypress leaf volatile oil; transferrin loaded with carbenoxolone brown; cationic liposomes loaded with nicotinamide mononucleotide, composed of DOTAP, DOPE, and cholesterol; PLGA nanoparticles loaded with salidroside, angelica polysaccharide extract, sodium hyaluronate, and lithium salt; The alcohol phase contains an ethanol solution of caffeine, as a cosolvent and solubilizing phase, promoting the interfacial fusion of the oil phase and the water phase; First, slowly add the alcohol phase to the oil phase under stirring, then slowly add the water phase, mix the three phases in proportion, and form a transparent, uniform, and thermodynamically stable microemulsion system through ultrasonic-assisted emulsification process.

3. The hair growth composition for enhancing microcirculation of hair follicle by using volatile oil of biota orientalis and alcohol extract of sorghum liquor according to claim 2, wherein the volatile oil of biota orientalis and the alcohol extract of sorghum liquor are mixed in a ratio of 1: 1 to 1:

10. The preparation of the PLGA nanoparticles loaded with sorghum wine alcohol extract includes the following steps: S1, extraction and concentration: active ingredients in the sorghum liquor were extracted by refluxing with 75% ethanol, and concentrated to a relative density of 1.05-1.10 at 60°C to obtain a sorghum liquor ethanol extract solution; S2, preparation of nanoparticle precursor solution: prepare an organic phase solution containing polylactic acid-glycolic acid copolymer; prepare an aqueous phase solution containing a surfactant; S3, mixing and nanoparticle formation in a microfluidic chip: the sorghum liquor ethanol extract solution, the organic phase solution containing polylactic acid-glycolic acid copolymer, and the aqueous phase solution containing a surfactant are introduced into different microchannels of a microfluidic chip, respectively; in the microfluidic chip, the sorghum liquor ethanol extract solution is mixed with the organic phase solution containing polylactic acid-glycolic acid copolymer to form an oil-in-water emulsion by precisely controlling the flow rate and mixing conditions of each solution; S4, the oil-in-water emulsion is formed into polylactic acid-glycolic acid copolymer nanoparticles by solvent evaporation, and the active ingredients in the sorghum liquor ethanol extract are uniformly wrapped in the polylactic acid-glycolic acid copolymer nanoparticles; S5, post-treatment: the formed nanoparticle solution is separated by centrifugation to remove excess surfactant and un-wrapped active ingredients; the nanoparticles are washed with deionized water several times to ensure that the surface of the nanoparticles is clean; the finally obtained nanoparticles are characterized by TEM and DLS to ensure that the size distribution of the nanoparticles is uniform and the active ingredients are uniformly dispersed The sorghum liquor ethanol extract is extracted by refluxing with 75% ethanol, concentrated to a relative density of 1.05-1.10, and treated by microfluidic technology to improve its stability, which includes wrapping the active ingredients in the sorghum liquor ethanol extract into nanoparticles.

4. The hair growth composition for enhancing microcirculation of hair follicle by using volatile oil of biota orientalis and alcohol extract of sorghum liquor according to claim 2, wherein the volatile oil of biota orientalis and the alcohol extract of sorghum liquor are mixed in a ratio of 1: 1 to 1:

10. The preparation of the transferrin loaded with acetyl tetrapeptide-3 and R-spondin1 mimic peptide includes the following steps: weigh 80 mg of lecithin, 20 mg of cholesterol, and 10 mg of sodium cholate into chloroform, and rotary evaporate to form a uniform lipid film; Add 2 mg of acetyl tetrapeptide-3 and 2 mg of R-spondin1 mimic peptide in pH 7.4 PBS buffer, and hydrate for 1 hour; Ultrasonic treatment at a power of 150 W for 3 min to obtain a transparent nanodispersion, filter through a 0.22 μm filter membrane, and store at 4°C.

5. The hair growth composition for enhancing the microcirculation of hair follicles by using the volatile oil of biota orientalis and the alcohol extract of sorghum liquor according to claim 2, characterized in that, The preparation of the nanostructured lipid carrier loaded with another part of volatile oil of Platycladus orientalis includes the following steps: weigh 60 mg of stearic acid, 40 mg of squalene, and another part of 20 mg of volatile oil of Platycladus orientalis, and melt at 75°C; Another aqueous phase: 20 mg of polysorbate 80 is dissolved in 10 mL of purified water, and heated to 75°C; Slowly add the oil phase to the aqueous phase, stir at a high speed of 10000 rpm for 5 min, and pre-emulsify; High-pressure homogenization at 1000 bar for 3 cycles; Cool to room temperature to obtain a white emulsion.

6. The hair growth composition for enhancing microcirculation of hair follicle by using volatile oil of biota orientalis and alcohol extract of sorghum liquor according to claim 2, wherein the volatile oil of biota orientalis and the alcohol extract of sorghum liquor are mixed in a ratio of 1: 1 to 1:

10. The preparation of the cationic liposome loaded with nicotinamide mononucleotide includes the following steps: Weigh 50 mg of DOTAP, 30 mg of DOPE, and 20 mg of cholesterol into chloroform, and rotary evaporate to form a uniform lipid film; Hydrate with 5 mg of HBS buffer containing nicotinamide mononucleotide at pH 7.0, 150 W, ultrasonic treatment for 3 min, filter sterilization.

7. The hair growth composition for enhancing microcirculation of hair follicle by using volatile oil of biota orientalis and alcohol extract of sorghum liquor according to claim 1, wherein the volatile oil of biota orientalis and the alcohol extract of sorghum liquor are mixed in a ratio of 1: 1 to 1:

10. The dosage form of the hair growth composition is a scalp serum, a spray, a gel or a soluble microneedle patch.

8. The method for preparing a hair growth composition for enhancing microcirculation of hair follicles by using volatile oil of Platycladus orientalis and alcohol extract of sorghum wine according to any one of claims 1 to 7, characterized in that, The method comprises the following steps: S1, respectively prepare the transferrin loaded with acetyl tetrapeptide-3 and R-spondin1 analog peptide, transferrin loaded with carbenoxolone brown, nanostructured lipid carrier loaded with another part of cypress volatile oil, and aqueous dispersion of cationic liposome loaded with nicotinamide mononucleotide; S2, mix the above nanoparticle dispersion, add the PLGA nanoparticles loaded with rhodioside, the PLGA nanoparticles loaded with sorghum wine alcohol extract, and lithium salt to form a complex aqueous phase; S3, dissolve a part of cypress volatile oil and hordenine in oil phase; S4, dissolve caffeine in ethanol as alcohol phase; S5, first slowly add the alcohol phase to the oil phase under stirring, and then slowly add the aqueous phase, mix the components in proportion to form a transparent microemulsion; through ultrasonic assisted emulsification process, a stable three-phase microemulsion is formed, and the hair growth composition for enhancing hair follicle microcirculation by using cypress volatile oil and sorghum wine alcohol extract is obtained.

9. A method of preparing a soluble microneedle patch for promoting hair growth, characterized by, The method comprises the following steps: S1, take 10 mL of the hair growth composition for enhancing hair follicle microcirculation by using cypress volatile oil and sorghum wine alcohol extract, mix with 50 mg of carboxymethyl chitosan, 30 mg of sodium alginate and 10 mg of glycerol, add water to 1 mL and stir uniformly; S2, inject into a microneedle mold, vacuum dry at 40°C for 12 h; S3, after demolding, the microneedle patch with a needle length of 300-600 μm is obtained, which is used for delivering drugs to the hair follicle papillary area, the needle body is transparent and completely dissolved in skin moisture within 10 min at room temperature.

10. The use of a hair growth composition for promoting hair follicle regeneration, improving hair density or delaying hair follicle aging, according to any one of claims 1 to 7, characterized in that, The product is an external preparation, preferably for topical use on the scalp.