WO2005000258A1 - Nanoparticules polymeres auto-assemblees contenant des ingredients physiologiquement actifs et application externe contenant les nanoparticules - Google Patents

Nanoparticules polymeres auto-assemblees contenant des ingredients physiologiquement actifs et application externe contenant les nanoparticules Download PDF

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WO2005000258A1
WO2005000258A1 PCT/KR2004/001572 KR2004001572W WO2005000258A1 WO 2005000258 A1 WO2005000258 A1 WO 2005000258A1 KR 2004001572 W KR2004001572 W KR 2004001572W WO 2005000258 A1 WO2005000258 A1 WO 2005000258A1
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self
physiologically active
hair
nanoparticles
acid
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PCT/KR2004/001572
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English (en)
Inventor
Yoon Sung Nam
Jong Won Shim
Byung Young Kang
Jae Sung Hwang
Jun Oh Kim
Ih Seop Chang
Won Seok Park
Hyung Seok Kang
Byung Seok Lee
Won Hee Cho
Dae Seok Sung
Dae Kwon Kim
Chang Hoon Lee
Sang Hoon Han
Young Chul Sim
Myeong Hoon Yeom
Sung Il Lee
Hyoung June Kim
Hye Jin Yang
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Amorepacific Corporation
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Priority claimed from KR1020030042703A external-priority patent/KR20040062379A/ko
Priority claimed from KR1020030087283A external-priority patent/KR100967113B1/ko
Priority claimed from KR1020040013452A external-priority patent/KR100551989B1/ko
Priority claimed from KR1020040044544A external-priority patent/KR101054731B1/ko
Priority claimed from KR1020040044542A external-priority patent/KR101054728B1/ko
Application filed by Amorepacific Corporation filed Critical Amorepacific Corporation
Priority to JP2006516956A priority Critical patent/JP4939936B2/ja
Publication of WO2005000258A1 publication Critical patent/WO2005000258A1/fr

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/02—Cosmetics or similar toiletry preparations characterised by special physical form
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/33—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing oxygen
    • A61K8/35—Ketones, e.g. benzophenone
    • A61K8/355—Quinones
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/63—Steroids; Derivatives thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/72—Cosmetics or similar toiletry preparations characterised by the composition containing organic macromolecular compounds
    • A61K8/90—Block copolymers
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q19/00—Preparations for care of the skin
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B82—NANOTECHNOLOGY
    • B82Y—SPECIFIC USES OR APPLICATIONS OF NANOSTRUCTURES; MEASUREMENT OR ANALYSIS OF NANOSTRUCTURES; MANUFACTURE OR TREATMENT OF NANOSTRUCTURES
    • B82Y5/00—Nanobiotechnology or nanomedicine, e.g. protein engineering or drug delivery
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2800/00—Properties of cosmetic compositions or active ingredients thereof or formulation aids used therein and process related aspects
    • A61K2800/40—Chemical, physico-chemical or functional or structural properties of particular ingredients
    • A61K2800/41—Particular ingredients further characterized by their size
    • A61K2800/413—Nanosized, i.e. having sizes below 100 nm
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2800/00—Properties of cosmetic compositions or active ingredients thereof or formulation aids used therein and process related aspects
    • A61K2800/40—Chemical, physico-chemical or functional or structural properties of particular ingredients
    • A61K2800/56—Compounds, absorbed onto or entrapped into a solid carrier, e.g. encapsulated perfumes, inclusion compounds, sustained release forms
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q1/00—Make-up preparations; Body powders; Preparations for removing make-up
    • A61Q1/02—Preparations containing skin colorants, e.g. pigments
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q11/00—Preparations for care of the teeth, of the oral cavity or of dentures; Dentifrices, e.g. toothpastes; Mouth rinses
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q19/00—Preparations for care of the skin
    • A61Q19/10—Washing or bathing preparations
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q5/00—Preparations for care of the hair
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q5/00—Preparations for care of the hair
    • A61Q5/02—Preparations for cleaning the hair
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q5/00—Preparations for care of the hair
    • A61Q5/12—Preparations containing hair conditioners
    • 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

  • the present invention relates to self-assembled polymeric nanoparticles containing physiologically active ingredients and to an external application containing the nanoparticles.
  • the present invention provides a self-assembled polymeric na oparticle having amphiphilic polymer, which comprises polycaprolactone as a hydrophobic block and polyethyleneglycol as a hydrophilic block to solubilize and to entrap physiologically active ingredients in an aqueous solution, and provides an external application for skin containing the particles.
  • nano-emulsion particles comprising medical substances, lipid, glycerol, water and phospholipid or nonionic surfactants are reported (USP 5,338,761), and other method having phospholipid with electronic charge as an emulsif ⁇ er is also reported (USP 6,120,751).
  • nano-emulsion is prepared by treating semi-formulated emulsion obtained by using surfactants having specific hrdrophilc-hydrophobic ratio with a high-pressure emulsifier (emulsifying machine), and liposome is a spherical or indeterminate formed particle having multi-layered membranes made of lipid from vegetables or animals in which various materials are captured.
  • the two formulations are widely used in cosmetics.
  • a method for preparing nanosized emulsion using microemulsions obtained when 3 phases of emulsif ⁇ er, oil and water get reached to a certain concentration USP 5,152,923, WO 91/06,286 and WO 91/06,287).
  • membranes of emulsion particles are in a state of dynamic equilibrium with outer phase, the ingredients in the emulsion contact with water, which causes oxidation or decomposition of the ingredient making the particles degenerated.
  • the membranes of the emulsion particles are chemically or physically weak and unstable, the membranes are easily broken by organic or inorganic pollutants, and a long-terms of storage is nearly impossible.
  • nanosized particles prepared by using low-molecular-weight emulsif ⁇ er are not sufficient to be used for unstable ingredients, and formulation thereof is difficult.
  • a large amount of surfactants should be used to contain high concentration of effective ingredients, which causes skin irritation.
  • using nanoemulsion particle has such effects that the effective ingredient therein are simultaneously released from the particle when applied to the skin because the membrane of the particle breaks on the skin or breaks in the skin after absorbed thereto, and that molecular design of membrane compound is possible which enables to decrease contact with outer phase.
  • a method using cochleate to minimize the contact of the inner materials with outer phase and to increase the release of ingredients is reported (USP 4,663,161).
  • the nanoparticles are very small and show colloidal instability
  • various surfactants or stabilizers are used in the conventional method and such procedures as high-pressure emulsification consuming a lot of energy should be applied to make nanosized particles.
  • the conventional methods have the problems of Ostwald ripening, precipitation or flocculation due to colloidal instability, and the colloidal instability becomes serious when the amount of solid components are increased, therefore the particles prepared by the conventional method can not contain a lot of effective ingredients (21th Proceedings of IFSCC International Congress, 2000(2000), 442-458).
  • various novel methods to capture the effective components stably have been studied, which is very important for external application, especially, in the field of cosmetics or pharmaceuticals.
  • the present invention relates to self-assembled polymeric nanoparticles containing physiologically active ingredients and to an external application containing the nanoparticles, in particular, to a self-assembled polymeric nanoparticle having amphiphilic polymeri, which comprises polycaprolactone as a hydrophobic block and polyethyleneglycol as a hydrophilic block to solubilize and to entrap physiologically active ingredients in an aqueous solution, and to an external application for skin containing the particles.
  • the self-assembled polymeric nanoparticles of the present invention are very useful to formulate and stabilize water-insoluble physiological components, this is because the polymeric nanoparticle of the present invention has a property of capturing insoluble components due to its self-assemble characteristic.
  • Physiological components that would be captured in the self-assembled polymeric nanoparticles of the present invention may comprise ginsenoside, co- enzyme Q10, active components for growing hairs such as f ⁇ nasteride and cyclosporin, but not restricted thereto.
  • the amphiphilic polymer having self-assembling characteristic and being applied to prepare the nanoparticle of the present invention is, preferably, a copolymer of hydrophobic biodegradable polycaprolactone (PCL, Formula 1; component "A”) and hydrophilic biodegradable polyethyleneglycol (PEG, Formula 2; component "B”).
  • PCL hydrophobic biodegradable polycaprolactone
  • PEG hydrophilic biodegradable polyethyleneglycol
  • the hydrophobic polymer may be PCL with a molecular weight of 500 to 100,000 daltons, more preferably, 1000 to 25,000 daltons.
  • the hydrophilic polymer may be PEG with a molecular weight of 500 to 100,000 daltons, more preferably, 1000 to 25,000 daltons.
  • the ratio of the PCL and the PEG is preferably 1 :9 to 9:1 by weight, more preferably 3:7 to 7:3, and most preferably, the ratio of the PCL and the PEG is 6:4 by weight.
  • n is an integer of 2 or more than 2.
  • m is an integer of 2 or more than 2.
  • the bonding of polycaprolactone and polyethyleneglycol of the present invention is preferably covalent bonding such as ester bonding, anhydride bonding, carbamate bonding, carbonate bonding, amine bonding, amide bonding, secondary amine bonding, urethane bonding, phosphodiester bonding or hydrazone bonding.
  • the physiological components captured and contained in the nanoparticle of the present invention may be such materials that can be solubilized in the polymer, especially, water-insoluble components that could not be formulated by the conventional method, for Example, ginsenosides, coenzyme Q10, hair growing components, but not restricted thereto.
  • ma-yuen and finasteride may be comprised therein.
  • ginseng saponins especially ginsenosides represented by Formula 3, for Example, ginsenoside Rhl, Rh2, Fl (Formula 4a) and compound K (Formula 4b) having a structure that a glucose is bonded to ginseng aglycon, and 20-O-[-L-arabinopyranosyl(l->6)-D-glucopyranosyl]-20(S)-protopanaxadiol having a structure that two glucoses are bonded to ginseng aglycon are useful for restricting proliferation of cancer cells or tumor cells, improving the activity of anticancer agents.
  • Rl, R3 is glucose or H; R2 is golucose, H or OH; and at least one of Rl, R2 and R3 is glucose.
  • Ginsenoside is a kind of ginseng saponin, and any type of ginsenoside can be applied in the present invention. That is, crude type extracted from ginseng or bio-transformed type can be applied. Ginsenosides represented by Formula 3 are preferable. [Formula 4a] [Formula 4b]
  • coenzyme Q10 represented by following Formula 5 may be usefully contained into the self-assembled polymeric nanoparticles of the presenti invention.
  • the self-assembled polymeric nanoparticles of the present invention may be applied to contain and carry the active components for growing and sprouting hairs that are effective but difficult to be formulated.
  • active components for growing and sprouting hairs comprises fmasteride, minoxidil, extracts of Thujae occidentalis, extracts of polygoni multiflori Radix, extracts of Glycyrrhiza uralensis, extracts of Coix lachryma-jobi var.
  • ma-yuen isoflavone, genistein, hesperetin, hesperidine, catechin, vitamin E and its derivatives, vitamin A its derivatives, provitamin D3 and its derivatives, ursolic acid, oleanolic acid, rosmarinic acid, 18-beta-glycyrrhetinic acid, farnesol, beta- sitosterol, linoleic acid, gamma linolenic acid, resveratrol, ceramide, Sphingosine, or the like.
  • cyclosporin an important immunosuppressive agent that is administered to a patient of organ transplantation by orally and used to treat psoriasis, was applied to the apopecia areata, and it is reported that cyclosporin has activities of growing hairs in the animal experiments.
  • Finasteride an active component for growing and sprouting hairs, is a specific inhibitor to the second type 5 ⁇ -reductase, and when it is orally administered, it prevents transformation of testosterone to dihydrotestosterone, so it is used for treating prostatitis or apopecia areata.
  • the above insoluble physiological components can be purchased or prepared by one skilled in the art to be applied to the present invention. And, vegetable extracts are easily obtained or prepared.
  • a method for preparing self-assembled polymeric nanoparticle containing physiologically active components comprises the following steps of: (a) Preparing amphiphilic polymer comprising polycaprolactone as a hydrophobic block and polyethyleneglycol as a hydrophilic block to form block copolymer; (b) Dissolving the amphiphilic polymer and physiologically active components in an organic solvent and stirring to prepare solution mixture; and (c) Pouring the solution mixture prepared through (a) and (b) a water solution to obtain nanoparticles; and (d) Removing organic solvent.
  • the amount of physiologically active components contained in the nanoparticles may be controlled according ' to its use and object, and preferably, 1 to 50wt% to the total weight of the nanoparticles, more preferably, 20 to 50wt%. When the amount of physiologically active components is more than 50%, the physiologically active components are not effectively entrapped and outflow from the nanoparticles, which causes cohesion and so causes discoloration or change of odor.
  • the mean size of the nanoparticles is preferably 1 to l,000nm, more preferably, 10 to 500nm.
  • Methods for preparing self-assembled polymeric nanoparticle containing physiologically active components using the PCL-PEG copolymer of the present invention in an aqueous solution comprises a method dispersing the PCL-PEG copolymer and applying supersonic waves; a method dispersing or dissolving the copolymer in an organic solution then removing the organic solvent by extracting with excessive water or by distilling away; a method dispersing or dissolving the copolymer in an organic solution and stirring severely with homogenizer or high pressure emulsifier then distilling away the solvent; a method dispersing or dissolving the copolymer in an organic solution then dialyzing with excessive water; a method dispersing or dissolving the copolymer in an organic solution then adding water slowly; or the like.
  • Organic solvent for biodegradable PCL-PEG copolymer to prepare polymeric nanoparticle of the present invention in an aqueous solution is at least one selected from the group consisting of acetone, dimethylsulfoxide, dimethylformamide, N-methylpyrolidone, dioxane, teterhydrofuran, ethylacetate, acetonitryl, methylethylketone, methylenechloride, chloroform, methanol, ethanol, ethylehter, diethylether, hexane, petroleum ether, or mixture thereof.
  • physiologically active components are captured in a hydrophobic core of the self-assembled polymeric nanoparticle and hydrophilic polymer chain is arranged on the surface of the nanoparticle, which makes the nanoparticle stably disperse in aqueous phase.
  • the nanoparticle dispersed in the aqueous phase has nanometer particle size and colloidal stability is very high.
  • the composition is stable because the physiologically active components do not directly contact with formulation components or with skin, and easily formulated as cream, lotion, cosmetic water, or the like.
  • the skin external application prepared above has the effects of the physiologically active components to improve skin, and shows improved absorption property into the skin, scalp or hair bulb.
  • the self-assembled amphiphilic polymer of the present invention is degraded in a body, and so very safe.
  • the formulation of the external application of the present invention is restricted and may be any formulation of hair tonic, scalp-treatment, hair cream, ointment, soft water, skin softener, nutrition water, eye cream, nutrition cream, massage cream, cleansing cream, cleansing foam, cleansing water, powder, essence, pack, body lotion, body cream, body oil, body essence, make-up base, foundation, hair dye, shampoo, rinse, body cleaner, tooth paste, oral cleaner, lotion, gel, patch or spray.
  • any components that are soluble to the solvent used for the preparation of the application may be selected and added by one skilled in the art according to its use and object.
  • Fig. 1 is a feature of self-assembled polymeric nanoparticle containing Q10 coenzyme taken by transmission electron microscope.
  • Fig. 2 is a feature of self-assembled polymeric nanoparticle containing the extracts of Thujae occidentalis taken by transmission electron microscope.
  • Fig. 3 is a feature of self-assembled polymeric nanoparticle containing ginsenoside taken by transmission electron microscope.
  • Fig. 4 is a feature of self-assembled polymeric nanoparticle containing minoxidil being absorbed into the hair bulb of the hairy Guinea.
  • Fig. 5 is a feature of self-assembled polymeric nanoparticle containing minoxidil being absorbed into the hamster flank organ.
  • the extract (1-butanol extract) was dissolved in a small amount of methanol, and a large amount of ethylacetate was added thereto to obtain precipitation.
  • the precipitation was dried to obtain lOOg of purified ginseng saponin extract (yield: 5%).
  • reaction mixture was extracted 3 times with same amount of ether then filtered and concentrated to obtain l,050mg of ginseng saponin mixture treated with enzyme comprising 440mg of Compound K, 150mg of ginsenoside Fl and other ginsenosides with 1-4 of glucose (yield: 10.5%).
  • PCL-PEG block copolymer The method for preparation of PCL-PEG block copolymer described in this Example is only for reference, the copolymer of the present invention is not restricted thereto.
  • the PCL-PEG block copolymer of the present invention was prepared by open-ring polymerization of polycaprolactone monomers. Specific amount of methoxy PEG [hereinafger, we call “mPEG” (Foumula 6)] and catalyst of Sn(Oct) 2 (Sigma, St.
  • the polymerization product was hard solid state, so the polymerization product was dissolved with 20ml of methylenechloride completely and precipitated with excessive ethylether. This procedure was repeated 3 times to remove not-reacted monomers and oligomers. The product of precipitation was vacuum dried at room temperature for 12 hours, and finally 17.3g of polycaprolactone-block-polyethyleneglycol block copolymer was obtained. It was verified by 1H NMR analysis that polycaprolactone at a terminal of monoethoxypolyehtyleneglycol was ring-opened to perform co-polymerization.
  • Preparation Examples 12-13 Preparation of block copolymer of polyethyleneglycol and poly-D,L-lactic acid-co-glycolic acid 5g of monomethoxypolyethyleneglycol (M.W 5,000) of which one terminal is hydroxy group, 7g of D,L-lactic acid and 3g of glycolic acid were added to a 20mL dried flask, and 0.025g of Sn(Oct) 2 as a catalyst was added thereto. A magnetic bar coated with Teflon was dropped to the flask, and the mixture underwent vacuum treatment for 30 minutes, then the flask was sealed tightly. The above sealed flask was put in 130 °C oil bath and performed polymerization for 6 hours.
  • M.W 5,000 monomethoxypolyethyleneglycol
  • Sn(Oct) 2 as a catalyst was added thereto.
  • a magnetic bar coated with Teflon was dropped to the flask, and the mixture underwent vacuum treatment for 30 minutes, then the flask was sealed tightly
  • the polymerization product was hard solid state, so the polymerization product was dissolved with 20ml of methylenechloride completely and precipitated with excessive ethylether. This procedure was repeated 3 times to remove not-reacted monomers and oligomers. The product of precipitation was vacuum dried at room temperature for 12 hours, and finally 12.7g of block copolymer of polyethyleneglycol and poly-D,L-lactic acid-co-glycolic acid. It was verified by 1H NMR analysis that D,L-lactic acid and glycolic acid at the terminal of monoethoxypolyehtyleneglycol was ring-opened to perform co-polymerization.
  • Mn number average molecular weight
  • Mn number average molecular weight
  • 2g of polyethyleneglycol having primary amine at a terminal [0,0'-Bis- (aminopropyl) polypropylene glycol-block-polyethylene glycol-block- polypropylene glycol; weight average molecular weight (Mw) 900] was added to 50ml reaction flask, and heated to 90 ° C to dissolve. The above dissolved solution was heated to 100 ° C, and 20g of poly-D,L-lactic acid-co-glycolic acid (RG502, Boehringer Ingelheim; Mw 11,000) was added, then stirred for 1 hour with lOOrpm.
  • Preparation Example 15 Preparation graft block copolymer of polyethylene- imine and polycaprolactone 2g of graft polyethyleneimine having primary amine at a terminal (Mw; 900) was added to 50ml reaction flask, and heated to 90 ° C to dissolve. The above dissolved solution was heated to 100 ° C, and 20g of polycaprolactone (Mw; 80,000) was added, then stirred for 1 hour with lOOrpm. The prepared homogeneous solution was stirred for 5 hours and cooled to room temperature.
  • the polymer product was dispersed and stirred in distilled water to purify and to remove not-reacted polyethyleneglycol, which was repeated 3 times, and finally obtained 21.2g of block copolymer of polyethyleneimine and polycaprolactone.
  • Preparation Example 16 Preparation linear block copolymer of polyethylene- imine and polycaprolactone 2g of linear polyethyleneimine having primary amine at a terminal (Mw; 900) was added to 50ml reaction flask, and heated to 90 °C to dissolve. The above dissolved solution was heated to 100 ° C, and 20g of polycaprolactone (Mw; 80,000) was added, then stirred for 1 hour with lOOrpm. The prepared homogeneous solution was stirred for 5 hours and cooled to room temperature. After completing reaction, the polymer product was dispersed and stirred in distilled water to purify and to remove not-reacted polyethyleneglycol, which was repeated 3 times, and finally obtained 19. lg of block copolymer of polyethyleneimine and polycaprolactone.
  • solvent mixture consisting of 25g of acetone and 25g ethanol and stirred homogeneously. After complete dissolution, the solution was poured slowly into 50ml of distilled water and stirred. After 1 minute of stirring, the solution was heated to 50 ⁇ 60 ° C and stirred again removing away solvent, and finally obtained dispersion solution of nanoparticles containing 2.5g of minoxidil.
  • the nanoparticle prepared in Example 3 of the present invention has better absorption property than microemulsion formulation about 159%.
  • the nanoparticle containing coenzyme Q10 of the present invention has better absorption property than liposome about 159%.
  • Example 4 Measurement of skin absorption of nanoparticles containing minoxidil
  • a fluorescent material Rubren
  • the nanoparticles prepared were applied on the skin of haircut hairy Guinea pig and on the flank organ of a hamster with a closed patch for 6 hours.
  • Obtained tissues were cut with 40j- ⁇ n thickness to prepare cryosection, then dyed with DAPI to mark nucleated cells (karyota), and the amount of Rubren absorbed into the skin through hair bulb was measured with confocal laser scanning microscopy (Zeiss). From the above result, it was found that the concentration gradient of the nanoparticles containing minoxidil absorbed into the skin was same throughout the skin, the concentration was high near the hair bulb and the nanoparticles were absorbed through hair bulb.
  • Liposome is a comparative experimental sample.
  • the nanoparticle of Example 51 of the present invention has better absorption property than liposome.
  • the nanoparticle of the Example 44 of the present invention containing minoxidil showed better hair-growing effect than the minoxidil of the same concentration
  • the nanoparticle of the Examples 41-43 of the present invention containing extracts of Thujae occidentalis showed better hair-growing effect than the extracts of Thujae occidentalis. From the results of Examples 41-43, it was found that the concentration of the active components and the ratio of the nanoparticles are important for the sprout or growth of the hairs.
  • Example 8 Effects of nanoparticles containing cyclosporin in the growth of hairs
  • the effects of the nanoparticles prepared in the Examples 48-59 were compared with those of hair-growing components not captured in the nanoparticles. Hairs on the backs of the mice 47-53 days from birth (C57BL/6) were removed, and 100 ⁇ Jl of the test samples were applied on the backs of the mice, 10 mice per sample, everyday. Hair-growing effects were valuated according to the length of hairs and degree of growth after removal of hairs scoring 0 to 3. In or to compare the hair- growing effects, 30% alcohol solution was applied to each mouth as a control. The results are shown in Table 13.
  • the nanoparticle of the Examples of the present invention showed better hair-growing effect than effective component of hair-growing itself at the same concentration, in addition, from the results of Examples 48, 51 and 54, it was found that the concentration of the active components are important in the sprout or growth of the hairs.
  • Example 10 Biosynthesis of collagen by the nanoparticles containing ginsenoside Human fibroblast was cultured in 24 well plate culture, and nanoparticles prepared by the method of Example 3 and microemulsions prepared according to following Comparative Example 1, which containing ginsenosides of the Table 15, were diluted to 1/100 and added to the culture. After 3 days of culture, 0.5ml of DMEM (Dulbecos modified eagles medium) containing 10% of fetal bovine serum (FBS) was added, and 10 g- Ci of L[2,3,4,5-3H]-proline was added.
  • DMEM Disulbecos modified eagles medium
  • FBS fetal bovine serum
  • TCA Terichloroacetic acid
  • ginsenoside captured in the nanoparticle of the present invention shows more excellent property of promoting biosynthesis of collagen compared with that of the ginsenoside not captured.
  • coenzyme Q10 in the polymeric nanoparticle of the present invention is more stable than that in the liposome during long terms of storage. Therefore, it is possible to maintain the activity of coenzyme Q10 by capturing coenzyme Q10 in the polymeric nanoparticle of the present invention.
  • Cream Formulation O/W emulsion composition comprising nanoparticles of the Examples 48, 51-53, 55, 57 is shown in Table 31. [Table 31]

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Abstract

La présente invention concerne des nanoparticules polymères auto-assemblées contenant des ingrédients physiologiquement actifs et une application externe contenant les nanoparticules, elle concerne notamment une nanoparticule polymère auto-assemblée ayant un polymère amphiphile, lequel contient une polycaprolactone en tant que bloc hydrophobe et du polyéthylène glycol en tant que bloc hydrophile pour solubiliser et piéger des ingrédients physiologiquement actifs dans une solution aqueuse, ainsi qu'une application externe pour la peau contenant les particules.
PCT/KR2004/001572 2003-06-27 2004-06-28 Nanoparticules polymeres auto-assemblees contenant des ingredients physiologiquement actifs et application externe contenant les nanoparticules WO2005000258A1 (fr)

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* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2005066196A1 (fr) * 2003-12-30 2005-07-21 Ranbaxy Laboratories Limited Forme amorphe de finasteride et procede de preparation associe
WO2006135512A1 (fr) * 2005-06-08 2006-12-21 Dow Global Technologies Inc. Composition de soins personnels
WO2007029983A1 (fr) * 2005-09-08 2007-03-15 Amorepacific Corporation Composition cosmetique pour eliminer le sebum contenant des catechines et des flavonols
WO2008123639A1 (fr) * 2007-04-09 2008-10-16 Bipl Co., Ltd Particule de nanoplatine-ginsénoside et procédé de production associé
WO2010089104A2 (fr) 2009-02-04 2010-08-12 Dsm Ip Assets B.V. Compositions de résveratrol
WO2011129588A2 (fr) * 2010-04-13 2011-10-20 (주)아모레퍼시픽 Composition de nanocomposite polymère/liposome pour absorption percutanée, et son procédé de préparation
US8252326B2 (en) 2005-06-01 2012-08-28 Catalent Australia Pty Ltd. Self-microemulsifying dosage forms of low solubility active ingredients such as co-enzyme Q10
CN103142457A (zh) * 2013-01-17 2013-06-12 西安电子科技大学 一种白藜芦醇纳米制剂的制备方法
US8541010B2 (en) 2010-07-13 2013-09-24 Woongjin Coway Co., Ltd. Cosmetic composition comprising double-shell nano-structure
WO2014032151A1 (fr) 2012-08-31 2014-03-06 Biolab Sanus Farmacêutica Ltda. Nanoparticule polymère de finastéride, suspension aqueuse la contenant, composition pour le traitement de l'alopécie, procédé de préparation de ladite composition, et son utilisation
WO2014032152A1 (fr) 2012-08-31 2014-03-06 Biolab Sanus Farmacêutica Ltda. Nanoparticule polymère de finastéride et de minoxidil, procédé pour sa préparation, suspension aqueuse la contenant, composition pharmaceutique, et son utilisation
CN103720752A (zh) * 2012-10-15 2014-04-16 马振友 一种生发和养发外用制剂及其制备方法
WO2014184173A1 (fr) * 2013-05-14 2014-11-20 Montero Gida Sanayi Ve Ticaret A.S. Formulations de soin capillaire
US9782485B2 (en) 2013-12-23 2017-10-10 Johnson & Johnson Consumer Inc. Topical gel compositions including polycaprolactone polymer and methods for enhancing the topical application of a benefit agent
CN107898816A (zh) * 2017-12-04 2018-04-13 中国药科大学 眼用药物制剂及其应用
GB2559221A (en) * 2016-09-05 2018-08-01 Spheritech Ltd Microparticle composition and use thereof
CN110200928A (zh) * 2019-07-23 2019-09-06 成秋宸 染料木素纳米冻干粉在抑制皮肤瘢痕形成和皮肤纤维化中的应用
US11000472B2 (en) 2015-04-06 2021-05-11 Lg Household & Health Care Ltd. Soluble microneedle for delivering poorly-soluble drug
KR20210083485A (ko) * 2019-12-26 2021-07-07 충북대학교 산학협력단 알피늄이소플라빈 가용화 조성물 및 이의 용도
CN114917356A (zh) * 2022-05-09 2022-08-19 广州中医药大学(广州中医药研究院) 一种用于调节雌激素的纳米复合物及其制备方法和应用

Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4474753A (en) * 1983-05-16 1984-10-02 Merck & Co., Inc. Topical drug delivery system utilizing thermosetting gels
US5543158A (en) * 1993-07-23 1996-08-06 Massachusetts Institute Of Technology Biodegradable injectable nanoparticles
KR19990069033A (ko) * 1998-02-04 1999-09-06 김윤 난용성 약물 함유 시스템
WO2002045689A1 (fr) * 2000-12-07 2002-06-13 Samyang Corporation Composition permettant la libération prolongée de médicaments hydrophobes, et procédé d'élaboration correspondant
KR20030045611A (ko) * 2001-12-04 2003-06-11 주식회사 삼양사 수용액에서 안정한 미셀 또는 나노 파티클을 형성하는고분자 조성물

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4474753A (en) * 1983-05-16 1984-10-02 Merck & Co., Inc. Topical drug delivery system utilizing thermosetting gels
US5543158A (en) * 1993-07-23 1996-08-06 Massachusetts Institute Of Technology Biodegradable injectable nanoparticles
KR19990069033A (ko) * 1998-02-04 1999-09-06 김윤 난용성 약물 함유 시스템
WO2002045689A1 (fr) * 2000-12-07 2002-06-13 Samyang Corporation Composition permettant la libération prolongée de médicaments hydrophobes, et procédé d'élaboration correspondant
KR20030045611A (ko) * 2001-12-04 2003-06-11 주식회사 삼양사 수용액에서 안정한 미셀 또는 나노 파티클을 형성하는고분자 조성물

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Publication number Priority date Publication date Assignee Title
WO2005066196A1 (fr) * 2003-12-30 2005-07-21 Ranbaxy Laboratories Limited Forme amorphe de finasteride et procede de preparation associe
US8252326B2 (en) 2005-06-01 2012-08-28 Catalent Australia Pty Ltd. Self-microemulsifying dosage forms of low solubility active ingredients such as co-enzyme Q10
WO2006135512A1 (fr) * 2005-06-08 2006-12-21 Dow Global Technologies Inc. Composition de soins personnels
JP2008543753A (ja) * 2005-06-08 2008-12-04 ダウ グローバル テクノロジーズ インコーポレイティド パーソナルケア組成物
WO2007029983A1 (fr) * 2005-09-08 2007-03-15 Amorepacific Corporation Composition cosmetique pour eliminer le sebum contenant des catechines et des flavonols
WO2008123639A1 (fr) * 2007-04-09 2008-10-16 Bipl Co., Ltd Particule de nanoplatine-ginsénoside et procédé de production associé
WO2010089104A2 (fr) 2009-02-04 2010-08-12 Dsm Ip Assets B.V. Compositions de résveratrol
US9572769B2 (en) 2010-04-13 2017-02-21 Amorepacific Corporation Polymer-liposome nanocomposite composition for percutaneous absorption, and method for preparing same
WO2011129588A2 (fr) * 2010-04-13 2011-10-20 (주)아모레퍼시픽 Composition de nanocomposite polymère/liposome pour absorption percutanée, et son procédé de préparation
WO2011129588A3 (fr) * 2010-04-13 2012-02-02 (주)아모레퍼시픽 Composition de nanocomposite polymère/liposome pour absorption percutanée, et son procédé de préparation
US8541010B2 (en) 2010-07-13 2013-09-24 Woongjin Coway Co., Ltd. Cosmetic composition comprising double-shell nano-structure
WO2014032151A1 (fr) 2012-08-31 2014-03-06 Biolab Sanus Farmacêutica Ltda. Nanoparticule polymère de finastéride, suspension aqueuse la contenant, composition pour le traitement de l'alopécie, procédé de préparation de ladite composition, et son utilisation
WO2014032152A1 (fr) 2012-08-31 2014-03-06 Biolab Sanus Farmacêutica Ltda. Nanoparticule polymère de finastéride et de minoxidil, procédé pour sa préparation, suspension aqueuse la contenant, composition pharmaceutique, et son utilisation
KR102128478B1 (ko) 2012-08-31 2020-07-01 바이오랩 세너스 팔마씨우티카 엘티디에이. 중합 피나스테리드 나노입자, 이를 포함한 수성 조성물, 탈모 치료를 위한 조성물 및 이의 제조 공정 및 이 조성물의 용도
KR20150044029A (ko) * 2012-08-31 2015-04-23 바이오랩 세너스 팔마씨우티카 엘티디에이. 중합 피나스테리드 및 미녹시딜 나노입자 및 이의 제조 공정, 이를 포함한 수성 현탁액, 약학적 조성물 및 이 조성물의 용도
KR20150046332A (ko) * 2012-08-31 2015-04-29 바이오랩 세너스 팔마씨우티카 엘티디에이. 중합 피나스테리드 나노입자, 이를 포함한 수성 조성물, 탈모 치료를 위한 조성물 및 이의 제조 공정 및 이 조성물의 용도
CN104768539A (zh) * 2012-08-31 2015-07-08 生物实验萨纽斯药物有限公司 非那雄胺聚合物纳米粒子、含有该粒子的水悬液、用于治疗脱发的组合物、制备所述组合物的方法及其用途
US9895302B2 (en) 2012-08-31 2018-02-20 Biolab Sanus Farmaceutica Ltda. Finasteride polymeric nanoparticle, aqueous suspension containing the same, composition for the treatment of alopecia, process of preparation of said composition, and its use
US9687554B2 (en) 2012-08-31 2017-06-27 Biolab Sanus Farmaceutica Ltda. Finasteride and minoxidil polymeric nanoparticle its process of preparation, aqueous suspension containing the same, pharmaceutical composition, and its use
AU2013308355B2 (en) * 2012-08-31 2017-08-31 Biolab Sanus Farmaceutica Ltda. Polymeric finasteride nanoparticle, aqueous composition containing same, composition for the treatment of alopecia, method for preparing said composition, and use thereof
AU2013308356B2 (en) * 2012-08-31 2017-09-28 Biolab Sanus Farmaceutica Ltda. Polymeric finasteride and minoxidil nanoparticles, method for preparing same, aqueous suspension containing same, pharmaceutical composition and use thereof
KR102118582B1 (ko) 2012-08-31 2020-06-04 바이오랩 세너스 팔마씨우티카 엘티디에이. 중합 피나스테리드 및 미녹시딜 나노입자 및 이의 제조 공정, 이를 포함한 수성 현탁액, 약학적 조성물 및 이 조성물의 용도
CN103720752A (zh) * 2012-10-15 2014-04-16 马振友 一种生发和养发外用制剂及其制备方法
CN103142457A (zh) * 2013-01-17 2013-06-12 西安电子科技大学 一种白藜芦醇纳米制剂的制备方法
WO2014184173A1 (fr) * 2013-05-14 2014-11-20 Montero Gida Sanayi Ve Ticaret A.S. Formulations de soin capillaire
US10022448B2 (en) 2013-12-23 2018-07-17 Johnson & Johnson Consumer Inc. Topical gel compositions including polycaprolactone polymer and methods for enhancing the topical application of a benefit agent
US9782485B2 (en) 2013-12-23 2017-10-10 Johnson & Johnson Consumer Inc. Topical gel compositions including polycaprolactone polymer and methods for enhancing the topical application of a benefit agent
US11000472B2 (en) 2015-04-06 2021-05-11 Lg Household & Health Care Ltd. Soluble microneedle for delivering poorly-soluble drug
GB2559221B (en) * 2016-09-05 2021-11-17 Spheritech Ltd Microparticle composition and use thereof
GB2559221A (en) * 2016-09-05 2018-08-01 Spheritech Ltd Microparticle composition and use thereof
US10500140B2 (en) 2016-09-05 2019-12-10 Spheritech Ltd. Microparticle composition and use thereof
CN107898816A (zh) * 2017-12-04 2018-04-13 中国药科大学 眼用药物制剂及其应用
CN110200928A (zh) * 2019-07-23 2019-09-06 成秋宸 染料木素纳米冻干粉在抑制皮肤瘢痕形成和皮肤纤维化中的应用
KR102300737B1 (ko) 2019-12-26 2021-09-13 주식회사 셀젠텍 알피늄이소플라빈 가용화 조성물 및 이의 용도
KR20210083485A (ko) * 2019-12-26 2021-07-07 충북대학교 산학협력단 알피늄이소플라빈 가용화 조성물 및 이의 용도
CN114917356A (zh) * 2022-05-09 2022-08-19 广州中医药大学(广州中医药研究院) 一种用于调节雌激素的纳米复合物及其制备方法和应用
CN114917356B (zh) * 2022-05-09 2023-03-10 广州中医药大学(广州中医药研究院) 一种用于调节雌激素的纳米复合物及其制备方法和应用

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