[go: up one dir, main page]

WO2020013179A1 - Composition d'absorption percutanée à libération contrôlée de minoxidil - Google Patents

Composition d'absorption percutanée à libération contrôlée de minoxidil Download PDF

Info

Publication number
WO2020013179A1
WO2020013179A1 PCT/JP2019/027141 JP2019027141W WO2020013179A1 WO 2020013179 A1 WO2020013179 A1 WO 2020013179A1 JP 2019027141 W JP2019027141 W JP 2019027141W WO 2020013179 A1 WO2020013179 A1 WO 2020013179A1
Authority
WO
WIPO (PCT)
Prior art keywords
fat
minoxidil
ketone group
transdermal absorption
complex
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Ceased
Application number
PCT/JP2019/027141
Other languages
English (en)
Japanese (ja)
Inventor
文靖 小野
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Kyushu University NUC
Nissan Chemical Corp
Original Assignee
Kyushu University NUC
Nissan Chemical Corp
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Kyushu University NUC, Nissan Chemical Corp filed Critical Kyushu University NUC
Priority to JP2020530197A priority Critical patent/JPWO2020013179A1/ja
Publication of WO2020013179A1 publication Critical patent/WO2020013179A1/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

Links

Images

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
    • A61K31/506—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
    • A61K47/10—Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
    • A61K47/14—Esters of carboxylic acids, e.g. fatty acid monoglycerides, medium-chain triglycerides, parabens or PEG fatty acid esters
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
    • A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
    • A61K47/54—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic compound
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/08—Solutions
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A61P17/14—Drugs for dermatological disorders for baldness or alopecia

Definitions

  • the present invention relates to a percutaneous absorption composition in which the release of minoxidil into the skin is controlled, and a method for controlling minoxidil in the skin.
  • the bond between the water-soluble drug and the fat-soluble site is broken by an enzyme or the like inside the skin, and the water-soluble drug is released.
  • an aqueous solution of a water-soluble drug is encapsulated in liposomes, dissolved and dispersed in an oily base material, and applied to the skin. After permeation of the stratum corneum, the interface of the liposome is disrupted inside the skin by enzymes or the like, and the water-soluble drug is released.
  • Patent Documents 1 to 5 Recently, it has been reported that a permeation enhancer (transdermal absorption enhancer) such as terpene or higher alcohol is used to enhance transdermal absorption of a drug.
  • a permeation enhancer transdermal absorption enhancer
  • terpene or higher alcohol is used to enhance transdermal absorption of a drug.
  • JP 2013-241449 A International Publication No. WO2012 / 043701 JP 2010-100650 A Japanese Patent No. 5680197 JP 2010-6771 A
  • Prodrug conversion is an excellent method for imparting lipophilicity to water-soluble drugs to enhance transdermal absorption, but it is a complicated process for the production process of organic synthesis and complicated procedures for obtaining approval for the manufacture and sale of drugs and quasi-drugs. Is required.
  • tranexamic acid an artificial amino acid, inhibits activation by binding to plasmin, a proteolytic enzyme, in the epidermis, thereby suppressing melanin production. It is known to. Utilizing this effect, in recent years, whitening effects have come to be claimed and have attracted attention as a raw material for cosmetics. However, there is a problem that the skin permeability of tranexamic acid is low.
  • An object of the present invention is to provide a method for easily increasing the transdermal absorbability of minoxidil without using a prodrug by organic synthesis.
  • the present inventors have conducted intensive studies and found that minoxidil forms a complex with a fat-soluble compound having a ketone group through an interaction, thereby easily giving the minoxidil a fat-solubility to promote the process.
  • the present inventors have found that minoxidil can be easily released into the skin while improving skin absorbability, and completed the present invention.
  • the present invention (1) a complex formed by interaction between minoxidil and a fat-soluble compound having a ketone group; (2)
  • the fat-soluble compound having a ketone group is at least one selected from the group consisting of a terpene having a ketone group, a lignoid having a ketone group, a vanilloid having a ketone group, a curcuminoid having a ketone group, chromone, and coumarin.
  • a composition comprising minoxidil, a fat-soluble compound having a ketone group, and a transdermal absorption controlling agent; (13) The composition according to the above (12), further comprising a fat-soluble medium; (14) The composition according to any of (8) to (13), wherein the transdermal absorption controlling agent is an alcohol; (15) The composition according to (14), wherein the alcohol is at least one selected from the group consisting of ethanol, geraniol, citronellol, and 1,2-hexanediol. (16) controlling the release of the minoxidil from the complex into the skin, comprising a step of dissolving the complex according to any one of the above (1) to (7) in a transdermal absorption controlling agent.
  • a method for releasing the minoxidil from the complex into the skin comprising a step of dissolving the complex according to any one of (1) to (7) in a transdermal absorption controlling agent; (18) a method of releasing minoxidil into the skin from a composition comprising minoxidil, a fat-soluble compound having a ketone group, and a transdermal absorption controlling agent; (19) a method for producing a complex formed by interaction between the minoxidil and the fat-soluble compound having a ketone group, comprising a step of mixing a powder of minoxidil and a fat-soluble compound having a ketone group; (20) a composition comprising the minoxidil, the fat-soluble compound having a ketone group, and the transdermal absorption controlling agent, comprising a step of mixing a powder of minoxidil, a fat-soluble compound having a ketone group, and a transdermal absorption controlling agent.
  • Method of manufacturing a product (21) The complex according to (1), wherein the essential
  • the complex of the present invention since minoxidil and the fat-soluble compound having a ketone group are complexed through an interaction, the complex can be uniformly dissolved (fat-solubilized or oil-solubilized) in the fat-soluble medium. As a result, the percutaneous absorbability of the minoxidil can be improved, and after permeation of the stratum corneum, the minoxidil can be released to exert a medicinal effect. In the present invention, the release of minoxidil from the complex in the skin can be controlled by appropriately using a transdermal absorption controlling agent.
  • the complex of the present invention minoxidil and the fat-soluble compound having a ketone group are complexed through an interaction. Therefore, the complex of the present invention can be in a chemical equilibrium relationship with minoxidil and the fat-soluble compound having the ketone group. As a result, in the fat-soluble medium, the complex is fat-solubilized by solvation or cluster formation. While it can exist stably, it dissociates and releases minoxidil inside the skin, so that it can exert its medicinal effect.
  • the complex of the present invention may be complexed through an interaction that can dissociate in water.
  • minoxidil may be used alone, or may be used in combination with one or more optional water-soluble active ingredients.
  • a water-soluble active ingredient of the present invention is not particularly limited as long as it is an active ingredient such as a water-soluble drug or cosmetic that can form a complex through interaction with a fat-soluble compound having a ketone group.
  • Any water-soluble pharmaceutical or cosmetic active ingredient for example, amino acids, hydrophilic vitamins, sugars, peptides and other hydrophilic drugs can be used.
  • Examples of such a water-soluble active ingredient of the present invention include those having an amino group, a hydroxyl group, or a thiol group.
  • ketone groups respectively have various interactions with the ketone group of the fat-soluble compound having a ketone group, for example, ionic bond, hydrogen bond, dipole interaction, van der Waals force, charge transfer interaction, ⁇ - It can form ⁇ interaction, hydrophobic interaction, solvation, reversible chemical bond, etc.
  • amino acid examples include artificial amino acids such as tranexamic acid; and alanine, arginine, asparagine, aspartic acid, cysteine, glutamine, glutamic acid, glycine, histidine, isoleucine, leucine, lysine, methionine, phenylalanine, proline, serine, threonine, tryptophan. , Tyrosine, and natural amino acids such as valine.
  • hydrophilic vitamin examples include ascorbic acid, sodium ascorbyl phosphate, magnesium ascorbyl phosphate, ascorbyl glucoside, ethyl ascorbic acid, and vitamins B1, B2, B4, B5, B6, B7, and B12.
  • sugar examples include glucose, trehalose, dextran, pullulan, cyclodextrin, mannitol, glucosamine, galactosamine, raffinose, mannan, and pectin.
  • peptides examples include known peptides and peptides having specific effects (for example, since they are recognized by human T cells, they are expected to have a therapeutic effect on hay fever). Specific examples include peptide A (amino acid sequence: QFAKLTGFTLMG) and peptide B (amino acid sequence: SMKVTVAFNQFGP).
  • hydrophilic drug examples include zanamivir (relenza), acyclovir, cytarabine ocphosphate, and fludarabine phosphate.
  • the fat-soluble compound having a ketone group of the present invention is not particularly limited as long as it is a fat-soluble compound containing at least one ketone group, and any compound containing an aliphatic ketone or an aromatic ketone can be used. . Above all, a fat-soluble compound having 4 or more carbon atoms, for example, 4 to 50 and having a ketone group is preferable. Further, from the viewpoints of natural origin and safety, terpene having a ketone group, lignoid having a ketone group, vanilloid having a ketone group, curcuminoid having a ketone group, chromone and coumarin having a ketone group are more preferable.
  • the tautomeric enol type: CC (OH)-can also be included in the ketone group in the present invention.
  • both ends of-(C O)-are bonded to carbon atoms.
  • Examples of the terpene having a ketone group include geranylacetone, camphor such as ( ⁇ ) -camphor, (+)-camphor, and ( ⁇ )-camphor, and carvone and capsanthin.
  • camphor such as ( ⁇ ) -camphor, (+)-camphor, and ( ⁇ )-camphor
  • carvone and capsanthin examples of the terpene having a ketone group
  • camphor is preferable, and a natural product such as an essential oil containing the above compound may be used.
  • camphor is used from the viewpoint of satisfactorily solubilizing minoxidil.
  • Essential oil is a general term for volatile organic matter produced by plants, and is generally a mixture of many compounds. There is no particular limitation, and the present invention can be implemented as long as the terpene having a ketone group of the present invention is contained.
  • camphor is a mixture of camphor as a main component (50 to 60%) and limonene (5 to 10%), ⁇ -pinene, myrcene and the like.
  • the sage is, for example, a mixture of camphor as a main component (20 to 30%), Cis-Thujong (15 to 20%), eucalyptol (10 to 15%), and the like.
  • lignoid having a ketone group examples include flavone.
  • Examples of the vanilloid having a ketone group include gingerol and shogaol.
  • curcuminoid having a ketone group for example, curcumin, demethoxycurcumin, bisdemethoxycurcumin and the like can be mentioned, and curcumin is preferable from the viewpoint of satisfactorily solubilizing minoxidil.
  • Examples of the aliphatic ketone and the aromatic ketone include methyl ethyl ketone, methyl isobutyl ketone, acetophenone, curcumin, and vitamin K.
  • the above-mentioned fat-soluble compounds having a ketone group may be used alone or in combination of two or more.
  • the lipophilic compound having a ketone group of the present invention is particularly preferably geranylacetone or (+)-camphor, from the viewpoint of satisfactorily solubilizing minoxidil.
  • the transdermal absorption controlling agent of the present invention is not particularly limited as long as it is commonly used for controlling transdermal absorption of active ingredients of water-soluble medicines or cosmetics in the field of medicines and cosmetics, especially skin external preparations.
  • a transdermal absorption controller having a hydroxyl group is preferable, and a monohydric or polyhydric alcohol is particularly preferably used.
  • a transdermal absorption controlling agent may be further complexed through an interaction. In such a conjugate, the release of minoxidil in the skin is better controlled.
  • Examples of the monohydric alcohol include lower alcohols such as methanol, ethanol, 1-propanol, and 2-propanol; higher alcohols; nerolidol, geraniol, menthol, borneol, isoborneol, nerol, citronellol, and fentyl.
  • Examples thereof include terpenes having a hydroxyl group such as alcohol, carveol, and neomenthol, and preferably include methanol, ethanol, citronellol, and geraniol.
  • Examples of the above higher alcohol include octanol, nonanol, decanol, undecyl alcohol, lauryl alcohol, tridecyl alcohol, myristyl alcohol, pentadecyl alcohol, cetyl alcohol, heptadecyl alcohol, stearyl alcohol, and fine oxocol 180 (FO180).
  • And C8-18 saturated alcohols such as oleyl alcohol, linoleyl alcohol, and linolenyl alcohol.
  • octanol, decanol, lauryl alcohol, myristyl alcohol, and oleyl alcohol are used, and more preferably, oleyl alcohol is used.
  • polyhydric alcohol examples include ethylene glycol, propylene glycol, 1,3-propanediol, 1,2-butanediol, 1,3-butanediol, 1,4-butanediol, 2,3-butanediol,
  • examples include 1,5-pentanediol, 1,2-hexanediol, glycerin, dipropylene glycol, diethylene glycol, triethylene glycol, and polyethylene glycol 400, and preferably include propylene glycol and 1,2-hexanediol. .
  • the complex of the present invention can be easily prepared by mixing the minoxidil and the fat-soluble compound having a ketone group, and heating and cooling for a certain period of time as necessary. From the viewpoint that a complex can be obtained favorably, it is preferable to add and mix the transdermal absorption control agent of the present invention, particularly the liquid transdermal absorption control agent. Further, the transdermal absorption controlling agent of the present invention is preferably in a liquid form in that the obtained complex can be stably dissolved. In this case, the solution of the obtained transdermal absorption control agent in which the complex is dissolved can be used for preparing the transdermal absorption composition of the present invention.
  • minoxidil When minoxidil is a solid (preferably a crystal), it is preferable to mix it in a powder form in order to obtain the composite of the present invention well.
  • a method for forming a powder include a method based on dry pulverization.
  • the conditions of the dry pulverization are not particularly limited as long as minoxidil can be pulverized into small pieces, but it is preferable to use a pulverizer such as a mortar, a ball mill, a homogenizer, a cutter mill, and a hammer mill.
  • the pulverizing time and the processing pressure are appropriately adjusted according to the hardness of the minoxidil to be pulverized.
  • the powder obtained by the above method is desirably further sieved to make the particle size uniform.
  • the sieve is preferably 500 ⁇ m or less, more preferably 200 ⁇ m or less, and particularly preferably 100 ⁇ m or less.
  • the mixing ratio between the minoxidil and the fat-soluble compound having a ketone group varies depending on the type of these substances used, but is 1: 1 to 100, preferably 1:10 to 50.
  • the mixing ratio of the minoxidil, the fat-soluble compound having a ketone group, and the percutaneous absorption controlling agent varies depending on the type of these substances used, but is 1: 1. 100100: 1 to 100, preferably 1: 1 to 100: 10 to 50, more preferably 1:10 to 50:10 to 50.
  • the composition ratio (molar ratio) of the minoxidil and the fat-soluble compound having a ketone group that constitutes the complex of the present invention is 1 to 100: 100 to 1, more preferably 1 to 10:10 to 1. is there.
  • the present invention by appropriately using the above-mentioned transdermal absorption controlling agent, particularly a monohydric or polyhydric alcohol, for example, depending on the type and the amount of these transdermal absorption controlling agents, in the skin after percutaneous absorption.
  • the release of minoxidil from the conjugate of the invention can be controlled.
  • the lipophilicity of the transdermal absorption controlling agent for example, by increasing the carbon number
  • the release of minoxidil of the present invention can be delayed, and the lipophilicity of the transdermal absorption controlling agent can be reduced.
  • the lipophilicity of the transdermal absorption controlling agent can enhance the release of minoxidil of the present invention.
  • the present invention also relates to a method of controlling the release of minoxidil from the complex in the skin, comprising the step of dissolving the complex of the present invention in a transdermal absorption controlling agent.
  • the present invention also relates to the use of a transdermal absorption control agent to control the release of minoxidil from the complex of the present invention in the skin.
  • the above-mentioned percutaneous absorption controlling agents may be used alone or in combination of two or more.
  • the fat-soluble medium of the present invention is not particularly limited as long as it is a fat-soluble medium commonly used as a base material in the field of medicines and cosmetics, especially skin external preparations, and is preferably a transdermal absorption promoting fat-soluble medium. Can be used.
  • the transdermal absorption-promoting fat-soluble medium is particularly limited as long as it is commonly used for promoting transdermal absorption of a water-soluble drug or an active ingredient of a cosmetic in the field of medicines and cosmetics, especially skin external preparations.
  • limonene eg, d-limonene
  • cyclopentasiloxane KF995: Isopropyl myristate (IPM), squalane, squalane, squalene, silicone oil, jojoba oil, almond oil, olive oil, horse oil, mineral oil, etc.
  • IPM isopropyl myristate
  • IPM isopropyl myristate
  • Cyclopentasiloxane squalane, limonene
  • the above-mentioned fat-soluble medium may be used alone or in combination of two or more.
  • the percutaneous absorption composition of the present invention can be prepared by mixing a solution of the percutaneous absorption control agent in which the complex obtained above is dissolved and the fat-soluble medium.
  • the complex of the present invention can exhibit good solubility in fat-soluble media by using an appropriate transdermal absorption control agent.
  • the fat-soluble medium is squalane, geraniol or citronellol is preferable as the transdermal absorption control agent, and when the fat-soluble medium is IPM, ethanol or 1,2-hexanediol is preferable as the transdermal absorption control agent.
  • the fat-soluble medium is KF995, geraniol or citronellol is preferred as the transdermal absorption control agent.
  • the transdermal absorption composition of the present invention may be used as such, but may be used as a conventional pharmaceutical preparation, particularly as a skin external preparation or cosmetic.
  • the pharmaceutical preparations or cosmetics are acceptable in the field of pharmaceuticals and cosmetics such as excipients, lubricants, binders, disintegrants, emulsifiers, stabilizers, flavoring agents, diluents, etc., so long as the effects of the present invention are not impaired. May be included.
  • the external preparation for skin of the present invention can contain components that can be usually blended in the external preparation for skin as long as the effects of the present invention are not impaired.
  • Such components include glycerin, polyhydric alcohols such as propylene glycol, liquid paraffin, squalane, higher fatty acids, oils such as higher alcohols, citric acid, organic acids such as lactic acid, caustic soda, alkalis such as triethanolamine, Cationic surfactants, amphoteric surfactants, nonionic surfactants, powders, pigments, dyes, preservatives and fungicides, resins, pH adjusters, antioxidants, ultraviolet absorbers, chelating agents, thickeners, Examples include humectants, alcohol, water, and fragrances.
  • the present invention also relates to a method for transdermally administering minoxidil, comprising applying the transdermal composition of the present invention to the skin.
  • the present invention also relates to the use of the transdermal absorption composition of the present invention for transdermal administration of the above-mentioned minoxidil.
  • the composition of the present invention may be a composition containing the minoxidil, the fat-soluble compound having a ketone group, and the transdermal absorption controlling agent, and is preferably a transdermal absorption composition.
  • the composition of the present invention may further contain the fat-soluble medium.
  • the present invention also relates to a method for transdermal administration of said minoxidil, comprising applying the composition of the present invention to the skin.
  • the invention also relates to the use of the composition of the invention for transdermal administration of said minoxidil.
  • percutaneous absorption test of minoxidil oil solubilized solution (1) The stratum corneum is hydrophobic and becomes more hydrophilic as it goes deeper. In other words, oil solubilization is an effective means for breaking through the stratum corneum barrier. Therefore, after permeating the skin barrier using an oil solubilized solution of minoxidil, a transdermal absorption test was performed to determine whether or not to release minoxidil in an aqueous PBS solution.
  • the transdermal absorption compositions used in this experiment are Comparative Example 1, Example 1, and Example 2 shown in Table 1 above.
  • the transdermal absorption test was performed as follows. As a transdermal absorption test, pig skin (Yucatan Micro Pig (Charles River Japan)) was used.
  • a stir bar and 5 mL of an aqueous PBS solution were added to the receiver phase of the Franz cell, the pig skin was sandwiched between the upper portions of the aqueous PBS solution, and water at 37 ° C. was flowed through the water jacket of the Franz cell.
  • the receiver phase was agitated and 200 ⁇ L of Comparative Example 1, Example 1, and Example 2 were placed on pig skin. Twenty-four hours later, a methanol extract of pig skin and a PBS aqueous solution of the receiver phase were sampled, and the amount of minoxidil was quantified by LC-MS.
  • the conditions of LC-MS are as follows.
  • Example of Preparation of Percutaneous Absorption Composition Containing Minoxidil Using IPM and Olive Oil as Oil Base Material In a 6 mL screw-neck sample tube, 42.5 mg of minoxidil, 42.5 mg of (+)-camphor, and 2000 mg of ethanol were placed. The mixture was stirred at room temperature for 30 minutes. Thirty minutes later, 1850 mg of IPM and 200 mg of olive oil were added to the obtained homogeneous ethanol solution to prepare a percutaneous absorption composition of Example 3 (minoxidil (1%) oil-solubilized solution).
  • the percutaneous absorption composition used in this experiment is a commercially available product 1 containing Minoxidil at a concentration of 5% (Reup ⁇ 5 Plus, Taisho Pharmaceutical), and Example 3.
  • the transdermal absorption test was performed as follows. As a transdermal absorption test, pig skin (Yucatan Micro Pig (Charles River Japan)) was used. A stir bar and 5 mL of an aqueous PBS solution were added to the receiver phase of the Franz cell, the pig skin was sandwiched between the upper portions of the aqueous PBS solution, and water at 37 ° C. was flowed through the water jacket of the Franz cell.
  • the receiver phase was agitated and 200 ⁇ L of Commercial Product 1 and Example 3 were placed on pig skin. Twenty-four hours later, a methanol extract of pig skin and a PBS aqueous solution of the receiver phase were sampled, and the amount of minoxidil was quantified by LC-MS.
  • the conditions of LC-MS are as follows. Column temperature: 30 ° C, detection mass (m / z): 210, eluent: 10 mM ammonium formate / acetonitrile (10/90, vol / vol), flow rate: 0.2 mL The results are shown in FIGS.
  • Example 3 the amount of minoxidil in porcine skin was detected about 9.7 times higher in Example 3 as compared with the commercial product 1. Further, the amount of minoxidil in the receiver solution was detected to be about 27.9 times larger in Example 3. Since the commercially available product 1 contains 5% minoxidil, the transdermal absorption composition of Example 3 (minoxidil (1%) oil-solubilized solution) used in this experiment promotes transdermal absorption, Promising as a transdermal drug delivery system (DDS) material.
  • DDS transdermal drug delivery system
  • the complex of the present invention can improve the transdermal absorbability of minoxidil, increase the content in the skin, and release minoxidil inside the skin to exert a medicinal effect.
  • the percutaneous absorption composition of the present invention containing the compound can be used as an external preparation for skin, for example, a drug or cosmetic used for external skin treatment.
  • a transdermal absorption control agent by appropriately using a transdermal absorption control agent, the release of minoxidil from the complex of the present invention inside the skin is controlled, so that it can be used for a drug delivery system.

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Epidemiology (AREA)
  • Engineering & Computer Science (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Oil, Petroleum & Natural Gas (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Dermatology (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Organic Chemistry (AREA)
  • Inorganic Chemistry (AREA)
  • Medicinal Preparation (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

Le but de la présente invention consiste à fournir un procédé d'amélioration de manière facile des propriétés d'absorption percutanée du minoxidil sans conversion en un promédicament par synthèse organique. La présente invention concerne : un complexe qui est formé au moyen d'une interaction du minoxidil avec un composé soluble dans les matières grasses ayant un groupe cétone ; une composition d'absorption percutanée comprenant le complexe, un agent de régulation de l'absorption percutanée, et un milieu soluble dans les matières grasses ; et un procédé de régulation de la libération du minoxidil dans la peau à partir du complexe.
PCT/JP2019/027141 2018-07-09 2019-07-09 Composition d'absorption percutanée à libération contrôlée de minoxidil Ceased WO2020013179A1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
JP2020530197A JPWO2020013179A1 (ja) 2018-07-09 2019-07-09 ミノキシジルの放出が制御された経皮吸収組成物

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
JP2018130174 2018-07-09
JP2018-130174 2018-07-09

Publications (1)

Publication Number Publication Date
WO2020013179A1 true WO2020013179A1 (fr) 2020-01-16

Family

ID=69141548

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/JP2019/027141 Ceased WO2020013179A1 (fr) 2018-07-09 2019-07-09 Composition d'absorption percutanée à libération contrôlée de minoxidil

Country Status (2)

Country Link
JP (1) JPWO2020013179A1 (fr)
WO (1) WO2020013179A1 (fr)

Citations (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPH10218737A (ja) * 1997-02-10 1998-08-18 Taisho Pharmaceut Co Ltd 育毛剤
JPH1112136A (ja) * 1997-06-27 1999-01-19 Taisho Pharmaceut Co Ltd ミノキシジル配合エアゾール剤
JP2004091354A (ja) * 2002-08-30 2004-03-25 Kanebo Ltd 養毛料
JP2005145900A (ja) * 2003-11-17 2005-06-09 Tsumura & Co 育毛剤組成物及び痒み抑制剤
JP2010100561A (ja) * 2008-10-23 2010-05-06 Mitsukan Group Honsha:Kk 毛様体筋緊張緩和剤
JP2010517938A (ja) * 2006-10-27 2010-05-27 ジュセッペ・トリジャンテ 抜け毛（脱毛）防止のための化合物と方法
WO2017094905A1 (fr) * 2015-12-02 2017-06-08 金印株式会社 Agent de régénération/stimulation de la pousse capillaire

Patent Citations (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPH10218737A (ja) * 1997-02-10 1998-08-18 Taisho Pharmaceut Co Ltd 育毛剤
JPH1112136A (ja) * 1997-06-27 1999-01-19 Taisho Pharmaceut Co Ltd ミノキシジル配合エアゾール剤
JP2004091354A (ja) * 2002-08-30 2004-03-25 Kanebo Ltd 養毛料
JP2005145900A (ja) * 2003-11-17 2005-06-09 Tsumura & Co 育毛剤組成物及び痒み抑制剤
JP2010517938A (ja) * 2006-10-27 2010-05-27 ジュセッペ・トリジャンテ 抜け毛（脱毛）防止のための化合物と方法
JP2010100561A (ja) * 2008-10-23 2010-05-06 Mitsukan Group Honsha:Kk 毛様体筋緊張緩和剤
WO2017094905A1 (fr) * 2015-12-02 2017-06-08 金印株式会社 Agent de régénération/stimulation de la pousse capillaire

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
BENN, S. ET AL.: "Potent Odorants in Peppermint and Cornmint Oils Characterized by GC-0 and AEDA", PERFUMER & FLAVORIST, vol. 23, no. 5, 1998, pages 5 - 16 *
ELAISSI, A. ET AL.: "Variation in Volatile Leaf Oils of Seven Eucalyptus Spiecies Harvested from Zerniza Arboreta( Tunisia)", CHEMISTRY & BIODIVERSITY, vol. 8, no. 2, 2011, pages 362 - 372, XP055675070 *

Also Published As

Publication number Publication date
JPWO2020013179A1 (ja) 2021-08-02

Similar Documents

Publication Publication Date Title
Nokhodchi et al. The effect of terpene concentrations on the skin penetration of diclofenac sodium
EP3159012B1 (fr) Nanoémulsions à phases continues et dispersées réversibles
JP7026914B2 (ja) 水溶性有効成分の放出が制御された経皮吸収組成物
JP2021518332A (ja) 親油性の活性薬剤の経皮及び／又は皮膚送達
Nokhodchi et al. The effect of glycyrrhizin on the release rate and skin penetration of diclofenac sodium from topical formulations
JP2009107930A (ja) 保湿剤及び皮膚外用剤
JP2013245205A (ja) 皮膚外用組成物及び化粧料
JP4294885B2 (ja) 複合エマルション及びそれからなる皮膚外用剤
JP2021042241A (ja) 外用組成物
JP2003160461A (ja) 皮膚外用剤
WO2021132529A1 (fr) Composition à absorption transdermique contenant de l'eau
WO2020013179A1 (fr) Composition d'absorption percutanée à libération contrôlée de minoxidil
JP2022158335A (ja) 水溶性有効成分を皮膚中へ浸透させ、かつ皮膚中に滞留させる方法
WO2019022250A1 (fr) Composition d'absorption percutanée contenant un ingrédient actif hydrosoluble à libération contrôlée
JP4594661B2 (ja) 油溶性アスコルビン酸誘導体を含有した乳化組成物
JPWO2020158831A1 (ja) 水溶性塩酸塩の放出が制御された経皮吸収組成物
CN107875038B (zh) 一种橄榄油微乳制剂及其作为美白防晒剂的应用
TW201919583A (zh) 含有水溶性有效成分及經皮吸收控制劑之溶液的調製方法
JP2020121938A (ja) 水溶性有効成分の放出が制御された水含有経皮吸収組成物
WO2019022249A1 (fr) Composition d'absorption transdermique à libération contrôlée de minoxidil
JPH11222412A (ja) 皮膚外用剤
JP5795146B2 (ja) 保湿剤及び皮膚外用剤
JP2003212751A (ja) ゲル組成物および水中油（ｏ／ｗ）型組成物
KR102139338B1 (ko) 인돌 화합물을 포함하는 용해도가 개선된 화장료 조성물
KR102139339B1 (ko) 인돌 화합물을 포함하는 용해도가 개선된 화장료 조성물

Legal Events

Date Code Title Description
121 Ep: the epo has been informed by wipo that ep was designated in this application

Ref document number: 19835120

Country of ref document: EP

Kind code of ref document: A1

ENP Entry into the national phase

Ref document number: 2020530197

Country of ref document: JP

Kind code of ref document: A

NENP Non-entry into the national phase

Ref country code: DE

122 Ep: pct application non-entry in european phase

Ref document number: 19835120

Country of ref document: EP

Kind code of ref document: A1