WO2006095778A1 - Nanoparticules contenant un ingredient stimulant la croissance des cheveux et leur procede de production, et stimulant de croissance de chevaux utilisant lesdites nanoparticules - Google Patents

Nanoparticules contenant un ingredient stimulant la croissance des cheveux et leur procede de production, et stimulant de croissance de chevaux utilisant lesdites nanoparticules Download PDF

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WO2006095778A1
WO2006095778A1 PCT/JP2006/304487 JP2006304487W WO2006095778A1 WO 2006095778 A1 WO2006095778 A1 WO 2006095778A1 JP 2006304487 W JP2006304487 W JP 2006304487W WO 2006095778 A1 WO2006095778 A1 WO 2006095778A1
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hair
growth
growth component
component
containing nanoparticles
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PCT/JP2006/304487
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English (en)
Japanese (ja)
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Hiroyuki Tsujimoto
Kaori Hara
Yusuke Tsukada
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Hosokawa Powder Technology Research Institute
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Priority to JP2007507154A priority Critical patent/JPWO2006095778A1/ja
Publication of WO2006095778A1 publication Critical patent/WO2006095778A1/fr

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q7/00—Preparations for affecting hair growth

Definitions

  • Hair-growth component-containing nanoparticles production method thereof, and hair-growth agent using the same
  • the present invention relates to a hair-growth component-containing nanoparticle in which a herbal medicine is encapsulated as a hair-growth component in the nanoparticle.
  • Alopecia includes male sex and juvenile alopecia (male pattern baldness), alopecia areata due to stress, and the like due to genetics and inheritance.
  • the hair does not develop sufficiently during the growth period in the above-mentioned hair cycle, and as a result, the hair moves to the regressing stage, resulting in hair loss in a state where the hair is thin and soft and the hair cycle is short. It is thought to occur.
  • DHT dihydrotestosterone
  • ATP adenosine triphosphate
  • hair loss is thought to have various causes, including blood circulation failure, nutritional disorders, inheritance, abnormal sebum secretion, and the occurrence of dandruff caused by the growth of resident scalp microorganisms. Yes.
  • Patent Document 1 uses jaundice extract as an active ingredient.
  • Patent Documents 2 and 3 disclose hair restorers that contain minoxidil and a herbal extract as active ingredients and that contain a polar solvent to improve the skin retention effect.
  • Patent Document 4 discloses a hair restorer composition containing an active ingredient and a water-swellable viscosity mineral and having excellent scalp permeability and usability.
  • Patent Document 5 an active ingredient is contained in an endoplasmic reticulum (ribosome) obtained by mixing phospholipid and water, and a beneficial substance is directly and selectively delivered to hair cells.
  • Patent document 6 discloses a hair-growth and hair-restoring composition comprising a hair-growth and hair-restoring agent held in small-diameter ribosomes produced using cluster-treated water.
  • Patent Document 7 discloses a transdermal absorbent containing a hair-growth agent as a physiologically active ingredient in polymer nanoparticles. Each is disclosed.
  • Patent Document 7 includes minoxidil, TGF (cell growth factor), EGF (epidermal growth factor), FGF (fibroblast growth factor), IGF (insulin-like growth factor), testosterone, androgen, etc.
  • TGF cell growth factor
  • EGF epidermal growth factor
  • FGF fibroblast growth factor
  • IGF insulin-like growth factor
  • Minoxidil which is described as an active ingredient, was originally developed as an antihypertensive agent, and some side effects have been pointed out over long periods of continuous use along with hormones such as testosterone and androgen.
  • Patent Document 7 describes halogenated alkanes, which are low-boiling and poorly water-soluble organic solvents, as an oil layer for dissolving a polymer and an active ingredient used in the production process of polymer nanoparticles.
  • Ethyl acetate, jetyl ether, cyclohexane, benzene, toluene, etc. are described, but these organic solvents are all concerned about toxicity to the human body and impact on the environment. It was not preferable to use it in the manufacturing process of hair growth and hair nourishing agents.
  • Patent Document 1 Japanese Patent Laid-Open No. 10-203933
  • Patent Document 2 JP-A-10-218737
  • Patent Document 3 Japanese Patent Laid-Open No. 2002-226329
  • Patent Document 4 Japanese Unexamined Patent Publication No. 2003-26546
  • Patent Literature 5 Japanese Patent Publication No. 8-511510
  • Patent Document 6 Japanese Unexamined Patent Publication No. 2000-229815
  • Patent Document 7 Japanese Patent Application Laid-Open No. 2002-308728
  • the present invention provides a hair-restoring ingredient-containing nanoparticle having a penetrating effect inside the scalp and a sustained-release effect of the ingredient and having high safety, and a hair-restoring agent using the same.
  • the purpose is to do.
  • Another object of the present invention is to provide a method for producing hair-growth-component-containing nanoparticles at low cost and with low environmental impact.
  • the present invention encapsulates one or more herbal components in a biocompatible polymer to form hair-growth component-containing nanoparticles.
  • the herbal medicine component is one or more selected from a matrix cell activator or an anti-inflammatory agent.
  • the hair matrix cell active agent is hinokitiol.
  • the anti-inflammatory agent is ⁇ -glycyrrhetinic acid.
  • the present invention provides the hair-growth component-containing nanoparticles having the above-described configuration
  • the present invention provides the hair-growth component-containing nanoparticles having the above-described configuration
  • the encapsulation rate of the herbal component in the biocompatible high molecule is 1 wt% or more and 20 wt% or less.
  • the biocompatible high molecule is a lactic acid / glycolic acid copolymer.
  • the average particle size is 30 nm or more and 300 nm or less.
  • the hair-growth component-containing nanoparticles having the above-described configuration are combined.
  • vitamins or vitamin derivatives are combined with the hair-growth component-containing nanoparticles having the above-described configuration.
  • sugar alcohol is complexed with the hair-growth component-containing nanoparticles having the above-described configuration.
  • the present invention is a hair restorer obtained by dispersing the hair-growth component-containing nanoparticles having the above-described configuration in a dispersion.
  • the hair-restoring component blended in the dispersion is vitamin or a vitamin derivative.
  • the present invention also provides nanoparticle formation in which a hair-growth component-containing biocompatible nanoparticle is formed by adding at least a crude drug, a biocompatible polymer and an organic solvent to an aqueous polyvinyl alcohol solution to form a hair-growth component-containing biocompatible nanoparticle. It has a process and the solvent distillation process of distilling off the said organic solvent from the said nanoparticle containing solution, It is a manufacturing method of the hair-growth component containing nanoparticle characterized by the above-mentioned.
  • the present invention provides a method of manufacturing hair growing ingredient-containing nanoparticles having the above structure, poly Bulle alcohol concentration in the poly Bulle aqueous alcohol was as this is less than 0.5 wt 0/0.
  • the present invention provides a method for producing the hair-growth component-containing nanoparticles having the above-described configuration, further comprising a removal step of removing the nanoparticle-containing solution force polybulu alcohol after the solvent distillation step.
  • the present invention provides the method for producing the hair-growth component-containing nanoparticles having the above-described structure, wherein the polybulal alcohol concentration in the aqueous polybulal alcohol is 0.1 wt% or more and 10 wt%
  • the organic solvent is a mixed solution of acetone and ethanol.
  • the present invention provides a method for producing a hair-growth component-containing nanoparticle having the above-described structure, wherein the nanoparticle is further combined after the solvent distillation step or the removal step. It was decided to have a degree.
  • the present invention provides a method for producing a hair-growth component-containing nanoparticle having the above-described configuration, wherein in the compounding step, at least one of sugar alcohol, vitamin, and vitamin derivative is combined with the nanoparticle. It was decided to make it.
  • the compounding step is performed by freeze-drying.
  • FIG. 1 In Example 11, apply j8-glycyrrhetinic acid PBS dispersion (Fig. 1 (A)) and ⁇ -glycyrrhetinic acid encapsulated PLGA nanoparticle aqueous dispersion (Fig. 1 ( ⁇ )) of the present invention.
  • 4 is a fluorescence intensity graph and a cross-sectional photograph of the epidermis after 4 hours.
  • FIG. 2 Fluorescence intensity graph and cross section of epidermis 4 hours after application of hinokitiol PBS dispersion (Fig. 2 ( ⁇ )) and hinokitiol-encapsulated PLG ⁇ nanoparticle aqueous dispersion (Fig. 2 ( ⁇ )) of the present invention It is a photograph.
  • FIG. 3 is a photograph showing the hair growth status of C3H mice in which test solution A of the present invention was applied to the entire shaved area in Example 12.
  • FIG. 4 is a photograph showing the hair growth of C3H mice in which test solution B of the present invention was applied to the entire shaved area.
  • FIG. 5 is a photograph showing the hair growth of C3H mice in which hair growth agent R as a comparative control solution was applied to the entire shaved area.
  • FIG. 6 is a photograph showing the hair growth of C3H mice in which hair growth agent I as a comparative control solution was applied to the entire shaved area.
  • FIG. 7 is a photograph showing the hair growth of C3H mice in which hair growth agent G as a comparative control solution was applied to the entire shaved area.
  • Herbal medicine mainly refers to medicinal herbs that have been used as natural medicines over the long history of centuries, and the main ingredients of this herbal medicine are herbal ingredients.
  • the hair-growth component-containing nanoparticle according to the present invention is obtained by encapsulating a crude drug component having a hair-growth effect in a biocompatible polymer to form a nano-sized particle.
  • This nanoparticle can also prevent pores and scalp surface force deep in the scalp. It can be suitably used as a hair restorer material because it allows the herbal components to reach the deep scalp and gradually release the hair growth component from the nanoparticles in the deep scalp. .
  • the biocompatible polymer used in the present invention is desirably biocompatible with low irritation to the living body and low in toxicity, and is biodegradable after being decomposed and metabolized. Further, it is preferably a particle that continuously and gradually releases the encapsulated drug.
  • a material in particular, polylactic acid / glycolic acid copolymer (PLGA) can be suitably used. It is known that PLGA can contain a drug and can be stored for a long time while retaining the efficacy of the drug. Furthermore, the hydrolysis of PLGA's 'long-term half-life' suggests that it can be sustainedly released in units of several days.
  • the molecular weight of PLGA is preferably in the range of 5,000 to 200,000, and more preferably in the range of 15,000 to 25,000.
  • the composition ratio of lactic acid to glycolic acid may be 1:99 to 99: 1, but glycolic acid is preferably 0.333 to lactic acid 1.
  • PL GA having a content of lactic acid and dalicholic acid in the range of 25% to 65% by weight is preferably used because it is amorphous and soluble in an organic solvent such as acetone. .
  • the surface of PLGA is made of polyethylene glycol.
  • Modification with (PEG) is preferable because the affinity between the crude drug component and PLGA is improved and encapsulation becomes easy.
  • Other biocompatible polymers include polyglycolic acid (PGA), polylactic acid (PLA), polyaspartic acid, and the like.
  • these copolymers such as aspartic acid / lactic acid copolymer (PAL) or aspartic acid / lactic acid / glycolic acid copolymer (PALG) may be used. It may have a group to obtain.
  • biocompatible polymers include polyalkylenes such as polyamide, polycarbonate, and polyethylene, polypropylene, polyethylene glycol, polyethylene oxide, polyethylene terephthalate, polybulal alcohol, polybull ether, and polybull ester.
  • polybulu compounds polymers of acrylic acid and methacrylic acid, cellulose and other polysaccharides, and peptides or proteins, or copolymers thereof. Examples include polymers or mixtures.
  • the herbal components included in the hair-growth component-containing nanoparticles of the present invention include hair matrix cell activators, anti-inflammatory agents, androgen antagonists, blood circulation promoters, bactericidal and antibacterial agents, and the like. And various herbal medicine components.
  • the hair matrix active agent acts directly on hair matrix cells and hair root cells, or increases ATP, which is an energy source for cell division, to activate cell division.
  • Such hair matrix activators include panthenol, pantothenic acid lucum, pantothenic acid ethyl, pantothel ether, and other panthenol derivatives, hinokitiol, potassium aspartate, pentadecanoic acid glyceride, photosensitizer 301, N Acetyl-L-methionine, 5-mono-trogoiacol, mono-trogoiacol sodium, chlorhexidine dalconate, biotin, netacanal, chixenin ginseng, taisou extract, placenta extract, carrot extract, royal jelly extract, garlic component, etc. Is mentioned.
  • An anti-inflammatory agent suppresses inflammation of the scalp and suppresses dandruff and itching.
  • Such anti-inflammatory agents include ⁇ -glycyrrhetinic acid and its derivatives, fat-soluble glycyrrhetinic acids, glycyrrhizic acid derivatives such as glycyrrhizic acid and dipotassium glycyrrhizinate, monoammoyl glycyrrhizinate, diphenhydramine hydrochloride, hydrocortisone acetate, brednisolone, salicylic acid , Azulene, guaiazulene, licorice extract, age extract, argon extract, shikon extract, power walnut extract, kikiyou extract, kiyonin extract, gardenia extract, kumana extract, gentian extract, comfrey extract, hawthorn extract, birch extract, cicada mushroom extract, Examples include
  • a male hormone antagonist like a 5a reductase inhibitor, suppresses the activity of male hormones that slow down the division of hair matrix cells.
  • male hormone antagonists include estradiol, ethynyl estradiol, spironolatatone, oxendron, jetinorestino lestrone, epitestosterone, estrone, cyproterone acetate, 11 ⁇ -hydroxyprogesterone, flutamide, 3 deoxyadenosine , Magnumone acetate, hop extract, peppermint extract, thiodi extract, quina extract, aloe extract, salamander extract, ginseng extract and the like.
  • the blood circulation promoter increases blood flow by dilating capillaries and promotes nutrient supply to the hair papilla.
  • Such blood circulation promoters include nicotinic acid derivatives such as nicotinic acid and -cotinamide, benzil nicotinate, cephalanthin, carbamine chloride, acetylcholine, ⁇ oryzanol, cerretin, cromakalim, nicorandil, pinacidil , Phthalides, dialkylmonoamine derivatives, yew extract, force honey kiss, toki extract, citrus extract, rosemary extract, assembly extract, bevana extract, pepper tincture, chimpi extract, ginger tincture, carrot extract, ginger root extract, Examples include medicinal extract and juice extract.
  • the bactericidal agent prevents the growth of various germs that have an adverse effect on hair growth.
  • fungicides include hinokitiol, isopropylmethylphenol, menthol, salicylic acid, benzalkonium chloride, otatovilox, black mouth hexidine, zinc pyrithione, potassium sorbate, biosol, kudin extract, muclojekis, ovata extract, etc. It is
  • a hair matrix cell active agent or an anti-inflammatory agent that acts directly on hair matrix cells or hair papilla present in the deep part of the scalp.
  • hinokitiol and ⁇ -glycyrrhetinic acid are suitable as herbal components to be encapsulated in nanoparticles because their effects are improved by supplying them to the deep part of the scalp as described later.
  • Hinokitiol is a substance contained in Aomori Hiba, Taiwan Hinoki, etc., and has both bactericidal and antibacterial effects in addition to cell activity.
  • ⁇ -Dalicyrrhetinic acid is one of the representative components of licorice, a kind of herbal medicine, and is known to have a wide range of physiological activities such as anti-ulcer activity and detoxification activity in addition to anti-inflammatory activity.
  • the encapsulation rate of these herbal medicine components in the nanoparticles is preferably 1% by weight to 20% by weight with respect to the biocompatible polymer, and more preferably 5% by weight to 20% by weight.
  • the hair-growth component-containing nanoparticle of the present invention is not particularly limited as long as it has an average particle size of less than lOOOnm, but it penetrates deep into the scalp. In order to enhance the effect, it is preferable to have an average particle size of 300 nm or less. Also, the skin cell size is 15, OOOnm, and the skin cell spacing is fluctuating between shallow and deep skin, but it is considered to be around 70nm, so the average particle size of nanoparticles is 200nm or less. By doing so, it becomes a nanoparticle that penetrates from the part other than the pores to the deep part of the scalp. On the other hand, as described above, the smaller the particle size of the nanoparticles, the lower the encapsulation rate. Therefore, the average particle size is preferably 30 nm or more.
  • the nanoparticles obtained as described above can be formed into aggregated particles that can be redispersed when powdered by freeze-drying or the like (can be composited).
  • can be composited even when combined by applying compressive force and shearing force by fluidized bed dry granulation method or dry mechanical particle compositing method (for example, Mechano-Fusion System AMS (manufactured by Hosokawa Micron Co., Ltd.))
  • fluidized bed dry granulation method or dry mechanical particle compositing method for example, Mechano-Fusion System AMS (manufactured by Hosokawa Micron Co., Ltd.)
  • This makes it easy to handle agglomerated particles in which nanoparticles are collected before use, and it becomes composite particles that return to the nanoparticles and restore properties such as high reactivity when exposed to moisture during use.
  • the encapsulated hair-growth component is water-soluble, once the encapsulated hair-growth component leaks to the surface of the nanoparticle, it is dissolved again in the surrounding water. If this water is removed by lyophilization or the like, the hair-growth component is reduced by that amount, and the encapsulation rate varies. Therefore, it is preferable to combine organic or inorganic substances so that they can be redispersed, and to dry them with the nanoparticles as they are without removing the water in which the hair-growth ingredients are dissolved. For example, by applying sugar alcohol or sucrose, it is possible to effectively prevent variation in the encapsulation rate, and sugar alcohol or the like can be used as an excipient to improve the handleability of the nanoparticles.
  • sugar alcohol examples include mannitol, trenorose, sorbitol, erythritol, manolecitose, xylitol, etc.
  • trehalose is particularly preferable. Trehalose is also preferable from the viewpoint of improving the hair-growth effect by moisturizing action.
  • vitamins and prosthesis are further added to the surface of the composite particle (nanocomposite).
  • a drug such as a vitamin
  • a fast-acting drug that dissolves the composite particle surface force immediately after permeation of the scalp can be applied, in addition to the hair-growth component that is released gradually from the nanoparticle force.
  • PLGA composite particles can be given even quicker permeability (fast-acting penetrating action).
  • the drug to be combined is water-soluble, it is preferable because it dissolves quickly and exhibits a fast-acting effect.
  • Such drugs include vitamin A, vitamin B, vitamin C, vitamin D, vitamin E, vitamin, vitamin K, vitamin ⁇ ⁇ ⁇ ⁇ , vitamin U, carcin, ferulic acid, y-oryzanol, a-ribo.
  • chitosan that enhances mucoadhesion may be combined on the surface of the nanoparticles, or phospholipids (lecithin / phosphatidylcholine) may be combined to increase scalp affinity.
  • phospholipids lecithin / phosphatidylcholine
  • PEG polyethylene glycol
  • talc talc
  • the hair-growth component-containing nanoparticles produced in this way produce an effective hair-growth effect when used as a hair-growth agent dispersed in a dispersion.
  • PLGA is hydrolyzed when mixed with moisture, and the nanoparticle transport performance is lost in a short period of time. Therefore, when using as such a hair restorer, it is possible to store the dispersion and powder in separate containers and store them in a predetermined amount immediately before use.
  • a mixture of water and ethanol is preferably used.
  • the aggregation of nanoparticles occurs when the volume ratio of ethanol to water is 1Z2 or more, it is preferably in the range of 1/10 to 3/10.
  • the hair-growth component in the dispersion adsorbed on the surface of the nanoparticles is simultaneously absorbed in the deep scalp as the nanoparticles penetrate into the deep scalp. Therefore, more hair-growth ingredients can be supplied to the hair matrix cells and hair papilla.
  • hair-growth ingredients anti-inflammatory agents, bactericidal and antibacterial agents that also act on the scalp surface, moisturizers, local stimulants, antiseborrheic agents that act on the scalp to further enhance the hair-growth effect, or as described above
  • vitamins and vitamin derivatives are added, the immediate effect of these drugs on the scalp surface is ensured, and in the deep scalp, the effect of hair growth over a long period of time can be achieved by gradual release of herbal components from hair-growth component-containing nanoparticles. Can be expected.
  • the moisturizing agent adjusts the hair growth environment by making the scalp dry and soft.
  • moisturizers include trehalose, mayifa, sorbitol, soluble collagen, glycerin, chondroitin sulfate, tuberose polysaccharides, cordyceps, trisaccharide, urea, biohyaluronic acid, hyaluronic acid, vitamin C phosphate calcium Salt, Sodium pyrrolidone carboxylate, Propylene glycol, Buttonpi extract, Aroche extract, Placenta extract, Enmeiso extract, Hypericum extract, Oat extract, Barley extract, Orange extract, Seaweed extract, Cucumber extract, Gobouex , Shiitake extract, zio extract, duke extract, bean extract, grape leaf extract, prune extract, loofah extract, maikai extract, mini sasanishiki, lily extract, apple extract, etc. I can get lost.
  • the local stimulant has effects such as activation of scalp metabolism, strengthening of the scalp, and prevention of itching.
  • Examples of such local stimulants include camphor, capsicum tincture, norcolic acid-lylamide, menthol, pepper tincture, Dutch power rachi extract, cantharis tincture, salamander extract, chili oil, and radish radish extract.
  • the antiseborrheic agent excludes excessively secreted sebum that promotes hair loss, or suppresses sebaceous gland activity. Examples of such antiseborrheic agents include cashew extract, odoricosou extract, iow, thixolone, vanside, polysorbates, and lecithin.
  • any component other than the hair-growth component for example, alcohols such as ethanol and polyhydric alcohol, celluloses, surfactants, fats and oils, water-soluble polymers, colorants, and fragrances
  • alcohols such as ethanol and polyhydric alcohol
  • celluloses such as ethanol and polyhydric alcohol
  • surfactants such as ethanol and polyhydric alcohol
  • fats and oils such as celluloses
  • water-soluble polymers such as celluloses, surfactants, fats and oils
  • colorants for example, ethanol and polyhydric alcohol
  • fragrances for example, ethanol and polyhydric alcohol, celluloses, surfactants, fats and oils, water-soluble polymers, colorants, and fragrances
  • ultraviolet absorbers, preservatives and the like can be blended within a range that does not hinder the effects of the present invention.
  • the nanoparticles efficiently penetrate into the hair roots inside the pores where the hair matrix cells and hair papilla are present. That is, a droplet containing nanoparticles applied to the scalp is likely to move in a direction in which the interfacial energy decreases (direction of penetrating into the scalp) because the surface tension is reduced by the nanoparticles. Furthermore, adsorption from the inside of the scalp occurs with respect to the nanoparticles or water in the droplets, so that the nanoparticles are efficiently delivered to the hair root.
  • the herbal medicine components encapsulated in the nanoparticles are gradually released over a long period at the hair root.
  • the method for producing the hair-growth component-containing nanoparticles of the present invention is not particularly limited as long as the target substance can be processed into particles having a particle diameter less than lOOOnm. It is highly preferred to use a crystallization method.
  • Spherical crystallization is a method in which spherical crystal grains can be designed and processed by directly controlling their physical properties by controlling the crystal formation and growth process in the final process of compound synthesis.
  • Spherical crystallization methods can be divided into spherical granulation method (SA method) and emulsion solvent diffusion method (ESD method) according to the difference in the formation of crystallized crystals' aggregation mechanism.
  • the SA method is a method of forming a spherical granulated crystal by precipitating drug crystals using two kinds of solvents. Specifically, first, a poor solvent that hardly dissolves the target drug and a good solvent that can dissolve the drug well and can be mixed and diffused in the poor solvent are prepared. Then, the drug solution dissolved in the good solvent is dropped into the poor solvent with stirring. At this time, drug crystals are precipitated in the system by utilizing the transition from a good solvent to a poor solvent and a decrease in solubility due to temperature effects.
  • the ESD method forms an emulsion and then crystallizes the drug into a spherical shape by utilizing the mutual diffusion between the good solvent and the poor solvent.
  • the method Specifically, first, a drug solution dissolved in a good solvent is dropped into the poor solvent with stirring. At this time, since the drug and the good solvent have an affinity, the transfer of the good solvent to the poor solvent is delayed, and emulsion droplets are formed.
  • nanoparticles can be formed by a physicochemical method, and the resulting nanoparticles are almost spherical. Can be formed as easily as necessary.
  • the organic solvent which is a good solvent, is distilled off under reduced pressure (solvent distillation step) to obtain a hair-growth component-containing nanoparticle powder.
  • the obtained powder is composited as it is or by freeze-drying as necessary (composite step) to form composite particles, which are then filled into a container to obtain hair-growth component-containing nanoparticles.
  • the types of the good solvent and the poor solvent, and the type of the liquid crosslinking agent are determined according to the type of the target drug and the like, and are not particularly limited. Since it is used as a raw material for hair growth agents that are applied directly to the scalp, it is necessary to use a material that is highly safe for the human body and has a low environmental impact.
  • a poor solvent for example, a polybulal alcohol aqueous solution is preferably used, and as a good solvent, for example, a mixed solution of acetone and ethanol is preferably used.
  • a step (removal step) of removing polyvinyl alcohol by centrifugation or the like is provided after the solvent distillation step.
  • the concentration of the polyvinyl alcohol aqueous solution, the mixing ratio of acetone and ethanol, the conditions at the time of crystal precipitation, and the method of applying mechanical shear force are not particularly limited. If determined appropriately according to the particle size of the granulated crystals (in the nano-order case in the present invention), the concentration of the polyvinyl alcohol aqueous solution is higher! On the other hand, the redispersibility in water after drying is improved, but when the concentration of the polyvinyl alcohol aqueous solution exceeds a predetermined level, the viscosity of the poor solvent is increased, which adversely affects the diffusibility of the good solvent.
  • the method for producing the hair-growth component-containing nanoparticles of the present invention was studied.
  • a 2% by weight aqueous solution of polyvinyl alcohol (PVA: manufactured by Kuraray Co., Ltd.) was prepared and used as a poor solvent.
  • This good solvent was added dropwise to the previous poor solvent at 40 ° C and 400 rpm at a constant speed (4 mLZ), and ⁇ -darlicylretinic acid-encapsulated PLGA nanosphere was suspended by diffusion of the good solvent into the poor solvent. A liquid was obtained.
  • Lactic acid / glycolic acid copolymer (PLGA: PLGA7 520, manufactured by Wako Pure Chemical Industries), a biocompatible polymer, is dissolved in 20 mL of acetone, and then 300 mg of hinokitiol (manufactured by Takasago Fragrance) dissolved in 10 mL of ethanol is added and mixed. A good solvent was used. This good solvent is added dropwise to the previous poor solvent at 40 ° C and 400 rpm at a constant speed (4 mLZ), and a suspension of hinokitiol-encapsulated PLGA nanospheres is obtained by diffusion of the good solvent into the poor solvent. It was.
  • trehalose aqueous solution prepared by dissolving 2 g of trehalose (manufactured by Hayashibara) in 8 mL of purified water
  • trehalose aqueous solution prepared by dissolving 2 g of trehalose (manufactured by Hayashibara) in 8 mL of purified water
  • a dry powder of PLGA composite nanoparticles having an average particle size of 200 nm to 300 nm and good redispersibility in water was obtained.
  • the entrapment ratio of hinokitiol in PLG A nanoparticles was determined to be 6.6%.
  • Lactic acid / glycolic acid copolymer (PLGA: PLGA7 520, manufactured by Wako Pure Chemical Industries, Ltd.), a biocompatible polymer, is dissolved in 20 mL of acetone, and then 9.5 mL of capsicum tincture (manufactured by Maruzen Pharmaceutical) is added. Solvent was used. This good solvent is added dropwise to the previous poor solvent at 40 ° C and 400 rpm at a constant speed (4 mLZ), and the suspension of PLGA nanospheres filled with red pepper tincture by diffusion of the good solvent into the poor solvent. Got.
  • trehalose aqueous solution prepared by dissolving 2 g of trehalose (manufactured by Hayashibara) in 8 mL of purified water
  • a dry powder of PLGA composite nanoparticles having an average particle size of 200 nm to 300 nm and good redispersibility in water was obtained.
  • the encapsulation rate of red pepper tincture in PLG A nanoparticles was determined to be 1.8%.
  • This good solvent is added dropwise to the previous poor solvent at 40 ° C and 400 rpm at a constant speed (4 mLZ), and benzil nicotinate-encapsulated PLGA nanosphere is suspended by diffusion of the good solvent into the poor solvent. A liquid was obtained.
  • trehalose aqueous solution prepared by dissolving 2 g of trehalose (manufactured by Hayashibara) in 8 mL of purified water
  • trehalose aqueous solution prepared by dissolving 2 g of trehalose (manufactured by Hayashibara) in 8 mL of purified water
  • a dry powder of PLGA composite nanoparticles having an average particle size of 200 nm to 300 nm and good redispersibility in water was obtained.
  • the encapsulation rate of benzyl nicotinate in PLGA nanoparticles was quantified and found to be 8.9%.
  • This good solvent was dropped into the above poor solvent at 40 ° C and 400 rpm at a constant speed (4 mLZ), and the good solvent was diffused into the poor solvent, and j8-glycyrrhetinic acid-encapsulated PLGA nanospheres were added. A suspension of was obtained.
  • This good solvent is dropped into the above poor solvent at 40 ° C and 400 rpm at a constant speed (4 mLZ), and a suspension of hinokitiol-encapsulated PLGA nanospheres is obtained by diffusion of the good solvent into the poor solvent. It was.
  • This good solvent is added dropwise to the previous poor solvent at 40 ° C and 400 rpm at a constant rate (4 mLZ), and a suspension of pepper tincture-encapsulated PLGA nanospheres is formed by diffusion of the good solvent into the poor solvent. Obtained.
  • This good solvent was dropped into the above poor solvent at 40 ° C and 400 rpm at a constant speed (4 mLZ), and the good solvent was diffused into the poor solvent, and j8-glycyrrhetinic acid-encapsulated PLGA nanospheres were added. A suspension of was obtained.
  • a scalp penetration test was carried out by the modified Bronoff diffusion chamber method using the hair-growth component-containing PLGA nanoparticles prepared according to the methods of Examples 1 and 2 above.
  • Figure 1 shows the fluorescence intensity dull of the scalp 4 hours after application of ⁇ -glycyrrhetinic acid PBS dispersion ( Figure 1 ( ⁇ )) or ⁇ -glycyrrhetinic acid-encapsulated PLGA nanoparticle aqueous dispersion ( Figure 1 ( ⁇ )).
  • FIG. 1 As is apparent from FIG. 1, when the aqueous dispersion of PL8 nanoparticles encapsulated with j8-glycyrrhetinic acid of the present invention was applied, the scalp surface was thin, and deep fluorescence was observed toward the deep part of the scalp, and the fluorescence intensity was also observed. Was also observed deep in the scalp.
  • FIG. 2 is a cross-sectional photograph of the scalp 4 hours after application of hinokitiol PBS dispersion (Fig. 2 (A)) or hinokitiol-encapsulated PLGA nanoparticle aqueous dispersion (Fig. 2 (B)).
  • FIG. 2 as in FIG. 1, when the aqueous dispersion of hinokitiol-encapsulated PLGA nanoparticles of the present invention was applied, the scalp surface was thin, but deep fluorescence was observed toward the deep part of the scalp, and the fluorescence intensity was also observed. Also strongly observed over the scalp.
  • Example 11 the hair growth effect of ⁇ -daricylretinoic acid-encapsulated PLGA nanoparticles and hinokitiol-encapsulated PLGA nanoparticles that had good scalp permeability was evaluated using C3H mice.
  • This C3H mouse is characterized by the fact that the hair cycle enters a resting state when the hair is cut, and it has been shown that hair does not grow for 15 days after cutting.
  • FIGS. 3 to 4 are photographs showing the hair growth of C3H mice with test solutions A and B and hair growth agents R, I, and G applied to the entire shaved area.
  • Table 1 shows the observation of hair growth. The results are summarized.
  • X represents a state in which hair growth has not occurred
  • ⁇ represents a state in which hair has grown from a very small amount to a slight amount
  • ⁇ represents a state in which hair growth can be clearly confirmed.
  • the mice to which the test solutions A and B containing the hair-growth component-containing nanoparticles of the present invention were applied were applied. After a few days, hair began to grow, although only in a small amount, and hair growth was clearly confirmed 15 days after application.
  • j8-glycyrrhetinic acid or hinokitiol is dispersed
  • hair growth agent R showed no hair growth after 13 days of application, and only had further hair growth after 15 days of application. It was.
  • hair growth agent I began to shine thinly 13 days after application, and hair growth was clearly confirmed 15 days after application.
  • hair growth agent G showed no hair growth even after 15 days of application.
  • ⁇ -glycyrrhetinic acid and hinokitiol are markedly enhanced in hair growth effect by encapsulating in PLGA nanoparticles, and the effect is superior to that of commercially available hair restorer R and hair restorer G. It was confirmed that they were almost equivalent.
  • Hair growth agent I is a combination of several types of hair growth components, whereas test solutions A and B are
  • the dispersion As a method for producing the dispersion, ethanol-soluble components are gradually added and dissolved at room temperature with stirring, and purified water is added to the solution to make it uniform, followed by filtration. In this dispersion, the ⁇ -glycyrrhetinic acid-encapsulated PLGA nanoparticles and hinokitiol-encapsulated PLGA nanoparticles described above can be well dispersed. This makes it possible to apply it as a dissolving hair restorer. In addition, blended in the dispersion The types and blending amounts of the hair-growth components to be applied are merely examples, and may be appropriately set according to the herbal components encapsulated in the nanoparticles and the type of target alopecia.
  • the hair-growth component-containing nanoparticles of the present invention include a highly safe herbicide component with little side effects as a hair-growth component in a biocompatible polymer.
  • the component-containing nanoparticles penetrate into the pores and deep into the scalp where the surface of the scalp has hair roots, so that the herbal components can reach the deep part of the scalp (hair roots) and the deep part of the scalp (hair roots). Part)), it is possible to obtain highly safe hair-growth component-containing nanoparticles capable of maintaining an excellent hair-growth effect over a long period of time.
  • a hair matrix active agent such as hinokitiol that acts directly on hair matrix cells and hair papilla present in the deep part of the scalp or an anti-inflammatory agent such as ⁇ -glycyrrhetinic acid is used as a crude drug component.
  • an anti-inflammatory agent such as ⁇ -glycyrrhetinic acid
  • other herbal ingredients such as blood circulation promoters and male hormone antagonists are encapsulated together, it is expected that the hair-growth effect will be improved by the synergistic effect of the components having different action mechanisms.
  • the particle diameter of the nanoparticles increases in proportion to the encapsulation rate of the crude drug component, but the average particle diameter of the nanoparticles is 30 nm or more and 300 nm or less, and hair growth for a biocompatible polymer is performed. Contains 1% to 20% by weight of ingredients, so the average particle size of nanoparticles is limited to the ability to penetrate the pores of the scalp cells other than the pores and pores, while containing hair-growth ingredients It becomes the hair-growth component containing nanoparticle which raised the quantity.
  • a biocompatible polymer that can be incorporated into a hair-growth component with low irritation to a living organism and is metabolized by being decomposed after administration is used. Can be ensured, and the sustained release of the hair-growth component can be achieved.
  • hydrolysis of PLGA's long-term half-life makes it possible to release it on a monthly basis for several days.
  • the hair-growth component-containing nanoparticles are composited by freeze-drying or the like, they become agglomerated particles that are easy to handle when filled into a container.
  • sugar alcohol and vitamins are combined with nanoparticles, the dispersibility and heat resistance of the combined nanoparticles are improved, and even if the hair-restoring ingredient to be encapsulated is water-soluble, it is encapsulated once.
  • the hair-growth effect can be improved by moisturizing action.
  • vitamins and vitamin derivatives are combined, the hair-growth effect of herbal ingredients and the hair-growth effect of vitamins act synergistically, and a more remarkable hair-growth effect can be expected.
  • the hair-growth component-containing nanoparticles are mixed and dispersed in a predetermined amount with the dispersion immediately before use, and used as a hair-growth agent to produce an effective hair-growth effect.
  • a hair-growth component is also added to the dispersion, it is adsorbed on the nanoparticle surface and delivered to the deep scalp together with the nanoparticle, so that more hair-growth components with different mechanisms of action are transferred to the hair matrix cells and hair. Can be supplied to the nipple.
  • the hair-growth component-containing nanoparticles of the present invention that form nanoparticles by using a spherical crystallization method can be easily used. And it can manufacture at low cost.
  • the concentration of the polybulal alcohol aqueous solution to which the drug, the biocompatible polymer and the organic solvent are added is 0.5% by weight or less, so that the nanobulb polyhydric alcohol aqueous solution is used as in the case of using the high concentration polybulal alcohol aqueous solution. Since there is no need for a removal step of removing excess polyvinyl alcohol by washing the particles by centrifuge separation, labor and time can be reduced, which is advantageous in production.

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  • Health & Medical Sciences (AREA)
  • Dermatology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Cosmetics (AREA)
  • Medicinal Preparation (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)

Abstract

L'invention concerne des nanoparticules contenant un ingrédient stimulant la croissance des cheveux préparées par encapsulation d'un ingrédient de médicament brut dans un polymère biocompatible afin de produire des particules de taille nanométrique. Ces nanoparticules pénètrent dans la partie profonde du cuir chevelu à partir des pores et de la surface dudit cuir chevelu. De ce fait, l'ingrédient de médicament brut peut être administré sur la partie profonde du cuir chevelu, puis progressivement libéré dans ladite partie profonde du cuir chevelu à partir des nanoparticules. En conséquence, ces nanoparticules sont appropriées pour être utilisées comme matériau pour stimulant de croissance des cheveux.
PCT/JP2006/304487 2005-03-10 2006-03-08 Nanoparticules contenant un ingredient stimulant la croissance des cheveux et leur procede de production, et stimulant de croissance de chevaux utilisant lesdites nanoparticules WO2006095778A1 (fr)

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Cited By (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2008179576A (ja) * 2007-01-25 2008-08-07 Yoshiro Nakamatsu 薬用育毛剤
JP2009079018A (ja) * 2007-09-27 2009-04-16 Kao Corp 頭皮用化粧料
JP2009107941A (ja) * 2007-10-26 2009-05-21 Hosokawa Funtai Gijutsu Kenkyusho:Kk 頭皮用育毛剤
JP2009120555A (ja) * 2007-11-16 2009-06-04 Fujifilm Corp 殺菌剤を内包した水分散可能なナノ粒子
JP2010006721A (ja) * 2008-06-25 2010-01-14 Fujifilm Corp タンパク質ナノ粒子を含むヘアトリートメント組成物
JP2010505800A (ja) * 2006-10-06 2010-02-25 ラボラトワール クラランス 脂性肌をケアするための化粧品組成物の使用
JP2010275249A (ja) * 2009-05-29 2010-12-09 Hosokawa Micron Corp 化粧料
JP2010275250A (ja) * 2009-05-29 2010-12-09 Hosokawa Micron Corp 化粧料

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* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2002056849A1 (fr) * 2001-01-17 2002-07-25 Biotech Inc. Stimulants de croissance capillaire
JP2002308728A (ja) * 2001-04-13 2002-10-23 Pacific Corp 高分子ナノ粒子を用いた経皮吸収剤及びこれを含有する外用剤
WO2003077886A1 (fr) * 2002-03-20 2003-09-25 Hosokawa Micron Corporation Procede de fabrication de particules composites contenant un produit chimique
JP2004262810A (ja) * 2003-02-28 2004-09-24 Hosokawa Funtai Gijutsu Kenkyusho:Kk 薬物含有複合粒子の製造方法および経肺製剤
WO2005072707A1 (fr) * 2004-01-28 2005-08-11 Hosokawa Powder Technology Research Institute Composition contenant des nanoparticules et son procédé de fabrication

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2002056849A1 (fr) * 2001-01-17 2002-07-25 Biotech Inc. Stimulants de croissance capillaire
JP2002308728A (ja) * 2001-04-13 2002-10-23 Pacific Corp 高分子ナノ粒子を用いた経皮吸収剤及びこれを含有する外用剤
WO2003077886A1 (fr) * 2002-03-20 2003-09-25 Hosokawa Micron Corporation Procede de fabrication de particules composites contenant un produit chimique
JP2004262810A (ja) * 2003-02-28 2004-09-24 Hosokawa Funtai Gijutsu Kenkyusho:Kk 薬物含有複合粒子の製造方法および経肺製剤
WO2005072707A1 (fr) * 2004-01-28 2005-08-11 Hosokawa Powder Technology Research Institute Composition contenant des nanoparticules et son procédé de fabrication

Cited By (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2010505800A (ja) * 2006-10-06 2010-02-25 ラボラトワール クラランス 脂性肌をケアするための化粧品組成物の使用
JP2008179576A (ja) * 2007-01-25 2008-08-07 Yoshiro Nakamatsu 薬用育毛剤
JP2009079018A (ja) * 2007-09-27 2009-04-16 Kao Corp 頭皮用化粧料
JP2009107941A (ja) * 2007-10-26 2009-05-21 Hosokawa Funtai Gijutsu Kenkyusho:Kk 頭皮用育毛剤
JP2009120555A (ja) * 2007-11-16 2009-06-04 Fujifilm Corp 殺菌剤を内包した水分散可能なナノ粒子
JP2010006721A (ja) * 2008-06-25 2010-01-14 Fujifilm Corp タンパク質ナノ粒子を含むヘアトリートメント組成物
JP2010275249A (ja) * 2009-05-29 2010-12-09 Hosokawa Micron Corp 化粧料
JP2010275250A (ja) * 2009-05-29 2010-12-09 Hosokawa Micron Corp 化粧料

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