WO2020226348A1 - 신규한 금속 층상수산화물 복합체 및 이의 제조방법 - Google Patents
신규한 금속 층상수산화물 복합체 및 이의 제조방법 Download PDFInfo
- Publication number
- WO2020226348A1 WO2020226348A1 PCT/KR2020/005706 KR2020005706W WO2020226348A1 WO 2020226348 A1 WO2020226348 A1 WO 2020226348A1 KR 2020005706 W KR2020005706 W KR 2020005706W WO 2020226348 A1 WO2020226348 A1 WO 2020226348A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- dipeptide
- tripeptide
- layered hydroxide
- metal layered
- tetrapeptide
- Prior art date
Links
Images
Classifications
-
- 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
- A61K47/52—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 inorganic compound, e.g. an inorganic ion that is complexed with the active ingredient
-
- 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
- A61K8/19—Cosmetics or similar toiletry preparations characterised by the composition containing inorganic ingredients
-
- 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
- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
- A61K31/365—Lactones
- A61K31/375—Ascorbic acid, i.e. vitamin C; Salts thereof
-
- 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
- A61K47/542—Carboxylic acids, e.g. a fatty acid or an amino acid
-
- 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
- A61K47/62—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 a protein, peptide or polyamino acid
-
- 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
- A61K47/69—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 conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit
- A61K47/6921—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 conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit the form being a particulate, a powder, an adsorbate, a bead or a sphere
-
- 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
- A61K47/69—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 conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit
- A61K47/6921—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 conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit the form being a particulate, a powder, an adsorbate, a bead or a sphere
- A61K47/6923—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 conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit the form being a particulate, a powder, an adsorbate, a bead or a sphere the form being an inorganic particle, e.g. ceramic particles, silica particles, ferrite or synsorb
-
- 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
- A61K8/0241—Containing particulates characterized by their shape and/or structure
- A61K8/0245—Specific shapes or structures not provided for by any of the groups of A61K8/0241
-
- 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
- A61K8/0241—Containing particulates characterized by their shape and/or structure
- A61K8/0254—Platelets; Flakes
- A61K8/0258—Layered structure
-
- 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
- A61K8/19—Cosmetics or similar toiletry preparations characterised by the composition containing inorganic ingredients
- A61K8/27—Zinc; Compounds 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
- A61K8/19—Cosmetics or similar toiletry preparations characterised by the composition containing inorganic ingredients
- A61K8/28—Zirconium; Compounds 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
- A61K8/30—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
- A61K8/36—Carboxylic acids; Salts or anhydrides thereof
- A61K8/361—Carboxylic acids having more than seven carbon atoms in an unbroken chain; Salts or anhydrides 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
- A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
- A61K8/40—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing nitrogen
- A61K8/44—Aminocarboxylic acids or derivatives thereof, e.g. aminocarboxylic acids containing sulfur; Salts; Esters or N-acylated 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
- A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
- A61K8/64—Proteins; Peptides; Derivatives or degradation products 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
- A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
- A61K8/64—Proteins; Peptides; Derivatives or degradation products thereof
- A61K8/65—Collagen; Gelatin; Keratin; Derivatives or degradation products 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
- A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
- A61K8/67—Vitamins
- A61K8/676—Ascorbic acid, i.e. vitamin C
-
- 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
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
- A61K9/50—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
- A61K9/51—Nanocapsules; Nanoparticles
- A61K9/5107—Excipients; Inactive ingredients
- A61K9/5115—Inorganic compounds
-
- 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
-
- 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
- A61Q19/08—Anti-ageing preparations
-
- 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
- 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
- A61K2800/10—General cosmetic use
-
- 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
- A61K2800/412—Microsized, i.e. having sizes between 0.1 and 100 microns
-
- 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
- A61K2800/58—Metal complex; Coordination compounds
-
- 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
- A61K2800/59—Mixtures
- A61K2800/596—Mixtures of surface active compounds
-
- 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
- A61K2800/60—Particulates further characterized by their structure or composition
- A61K2800/61—Surface treated
- A61K2800/62—Coated
- A61K2800/622—Coated by organic compounds
-
- 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
- A61K2800/60—Particulates further characterized by their structure or composition
- A61K2800/65—Characterized by the composition of the particulate/core
- A61K2800/651—The particulate/core comprising inorganic material
Definitions
- the present invention relates to a novel metal layered hydroxide complex comprising an active ingredient and a surface modifier of a peptide ingredient and a method for preparing the same.
- the surface treatment has been performed using heat treatment, ultrasonic treatment, or reconstruction methods.
- a surface treatment method has a problem that decomposition of active ingredients and releasing of unintended active ingredients may occur, treatment time is long, and related manufacturing facilities are required.
- the delamination or exfoliation method for surface modification of the metal layered hydroxide is a method using separation of a nanosheet through swelling, such as toluene, formaldehyde, dichloromethane, etc.
- a nanosheet through swelling such as toluene, formaldehyde, dichloromethane, etc.
- the use of an organic solvent was indispensably required, and there was a problem of post-treatment such as a washing process and bio-stability problems.
- due to the method of completely separating the nanosheet there was a problem in that unstable active ingredients could not be put into the layered structure to stabilize.
- TEOS and TMOS used as surface-modifying agents disclosed in conventional patents 10-0439299 and 10-0841700, etc. exhibit sustained-release properties by using silica as the main raw material, but due to the characteristics of silica, the stability of active ingredients is high because of moisture moisture.
- Lecithin, cellulose, xanthan gum, guar gum, methylcellulose, and hydroxypropylmethylcellulose listed in Korean Laid-Open Publication No. 10-2006-0132409 are a simple mixture that is not a physicochemical combination of a metal layer hydroxide and a modifier. As it is only a problem, particle size control and dispersion characteristics do not appear.
- High-temperature heat treatment or ultrasonic treatment method that changes the physical properties of the particle surface by etching the particle surface through the above-described conventional surface treatment method, around 100°C and ultrasonic treatment, and induces structural change of the particle by processing at a high temperature of 200°C or higher
- the reconstruction method, the polymer or dispersant adsorption method that adsorbs the polymer to the particle surface, the metal layered hydroxide peeling method using an organic solvent, and the surface modification method using functional groups require related manufacturing facilities, or Since the manufacturing process is complicated and an unsafe problem occurs due to the use of a hazardous solvent, an alternative modification method has been required.
- an object of the present invention is to provide a new metal layered hydroxide composite whose surface has been modified to solve the above problems.
- Patent Document 1 Registered Patent No. 10-0439299
- Patent Document 2 Registered Patent No. 10-0841700
- Patent Document 3 Publication No. 10-2006-0132409
- the present invention provides a metal layered hydroxide composite comprising an active ingredient and a surface modifier in order to solve the above problem, has a reduced particle size, stably contains the active ingredient, and the sustained-release effect thereof is significantly improved. It provides a metal layered hydroxide composite.
- the present invention can be synthesized simply by combining an active ingredient having an opposite charge with a metal layered hydroxide by electrostatic attraction, or by adjusting the internal structure of the metal layered hydroxide, that is, crystallinity, and no harmful substances are used. It is possible to safely manufacture a metal layered hydroxide composite without maximizing the synthesis efficiency and time, and provides an eco-friendly and economical manufacturing method.
- the present invention is an active ingredient; And as a metal layered hydroxide complex comprising a surface modifier, the active ingredient is ascorbic acid (ascorbic acid), biotin (biotine), pantothenic acid (pantothenic acid), cysteine (cysteine), ferulic acid (ferulic acid), glutamic acid ( glutamic acid), indole acetic acid, cinnamic acid, caffeic acid, thiamine, riboflavin, niacin, pantothenic acid, pyridoxine pyridoxine), folic acid, calciferol, tocopherol, transexamic acid, salicylic acid, retinoic acid, arbutin, etc. It is one or more selected from
- the surface modifier is a peptide containing 2 to 8 amino acids; And it provides a metal layered hydroxide complex comprising at least one selected from the group consisting of a peptide containing 2 to 8 amino acids and a peptide containing a fatty acid having 10 to 16 carbon atoms-fatty acid conjugate.
- the present invention comprises the steps of preparing a solution in which the precursor is dissolved by adding and dissolving an acidic solution to the precursor of the metal layered hydroxide complex; And mixing alcohol, distilled water, an active ingredient, and a surface modifier in a solution in which the precursor is dissolved to prepare a metal layered hydroxide composite.
- the present invention comprises the steps of preparing a solution in which the precursor is dissolved by adding and dissolving an acidic solution to the precursor of the metal layered hydroxide complex; Preparing crystal nuclei containing an active ingredient by mixing alcohol, distilled water, and an active ingredient in a solution in which the precursor is dissolved; And an ion exchange step of preparing a metal layered hydroxide composite for ion exchange by mixing a surface modifier with the prepared crystal nuclei, wherein the pH of the ion exchange step is 5 or more to 10 or less. Provides a way.
- the present invention provides a metal layered hydroxide composite comprising an active ingredient and a surface modifier, has a reduced particle size, stably contains the active ingredient, and has a remarkably excellent sustained-release effect.
- the present invention can be synthesized simply by combining an active ingredient having an opposite charge with a metal layered hydroxide by electrostatic attraction, or by adjusting the internal structure of the metal layered hydroxide, that is, crystallinity, and thus the treatment time is short and special It has an eco-friendly and economical effect in that it does not require manufacturing facilities.
- the manufacturing method of the present invention does not require post-treatment such as washing due to the use of organic solvents such as toluene, formamide, and dichloromathane, and thus has a safe effect without using harmful substances.
- 1 is a diagram for a method of forming a metal layered hydroxide complex by an external ion exchange method.
- FIG. 2 is a diagram of a metal layered hydroxide composite formed by an external ion exchange method.
- FIG. 3 is a diagram for a method of forming a metal layered hydroxide composite by a crossover insertion method.
- FIG. 4 is a diagram of a metal layered hydroxide composite formed by a crossover insertion method.
- 5 to 10 are XRD graphs of the metal layered hydroxide composite.
- 11 to 20 are photographs of measuring the Tindall effect on the metal layered hydroxide composite.
- 21 is an inner-outer structure diagram of a metal layered hydroxide composite (SMA 0.005: crystallinity controlled at a ratio of VitC 1) prepared by an external ion exchange method.
- SMA 0.005 crystallinity controlled at a ratio of VitC 1
- FIG. 22 is an inner-outer structure diagram of a metal layered hydroxide composite (crystallinity controlled at a ratio of SMA 0.5: VitC 0.5) prepared by a crossover insertion method.
- 23 and 24 are graphs for particle size evaluation results of a metal layered hydroxide composite.
- 25 and 26 are graphs for evaluation results of zeta potential of a metal layered hydroxide composite.
- 27 and 28 are graphs for particle size evaluation results of a metal layered hydroxide composite.
- 29 and 30 are graphs for the evaluation results of zeta potential of the metal layered hydroxide composite.
- 31 to 35 are graphs of sustained-release evaluation results of a metal layered hydroxide composite.
- the present invention is an active ingredient; And it provides a novel metal layered hydroxide composite comprising a surface modifier and a method of manufacturing the same.
- the metal layered hydroxide complex can be applied as a functional or pharmaceutical substance such as oral preparations, detergents, and shampoos depending on the type of material to be inserted (ex. surfactant, amino acid series), and the stability of the active ingredient is maintained and in a colloidal form. Since it can have the effect of reducing the particle size, it is possible to increase absorption when used as a cosmetic, and can have an excellent effect of sustained release of active ingredients.
- the sustained-release effect of the metal layered hydroxide composite of the present invention is to release the active ingredient at a release rate of 65% or less within 72 hours, more preferably to have a release rate of 30 to 60% within 72 hours.
- the metal layered hydroxide composite of the present invention may have a particle size (Z-average (d.nm)) of less than 1000 d.nm, more preferably 200 to 900 d.nm.
- the metal layered hydroxide composite may be a composite in which a metal and a hydroxide are combined.
- it may be represented by the following formula (1), but is not limited thereto.
- M 2+ is Mg 2+ , Ca 2+ , Co 2+ , Cu 2+ , Ni 2+ or Zn 2+ ,
- A is a biologically active substance carrying a negative charge
- x' is a number greater than 1 and less than 2;
- y is a number greater than 0 and less than or equal to 100;
- w is a number of 0 or 1).
- the active ingredient and the surface modifier are only for name classification, the surface modifier may serve as an active ingredient, and the active ingredient may serve as a surface modifier.
- the active ingredient is ascorbic acid, biotine, pantothenic acid, cysteine, ferulic acid, glutamic acid, indole acetic acid.
- indole acetic acid cinnamic acid, caffeic acid, thiamine, riboflavin, niacin, pantothenic acid, pyridoxine, folic acid ), calciferol (calciferol), tocopherol (tocopherol), tranexamic acid (Tranexamic acid), salicylic acid (salicylic acid), retinoic acid (retinoic acid) and arbutin (arbutin) can be at least one selected from the group consisting of have.
- the surface modifier is a peptide comprising 2 to 8 amino acids; And a peptide containing 2 to 8 amino acids and a peptide containing a fatty acid having 10 to 16 carbon atoms-at least one selected from the group consisting of a fatty acid conjugate.
- each peptide generally correspond to the abbreviations commonly used to express amino acids.
- the peptide comprising the 2 to 8 amino acids is specifically, dipeptide-1 (YR), dipeptide-2 (VW), dipeptide-4 (FW), dipeptide-6 (KV), dipeptide-7 ( KT), dipeptide-14 (AT), dipeptide (GH), acetyl dipeptide-1 (YR), acetyl dipeptide-1 cetyl Ester (YR), nicotinoyl dipeptide-2 (VW), CP dipeptide (CP), VGE dipeptide ( VE), CGE dipeptide (CE), EGE dipeptide (EE), TGE dipeptide (TE), LGE dipeptide (LE), EQ dipeptide (EQ), GR dipeptide (GR), HG dipeptide (HG), PE dipeptide (PE) , DE dipeptide (DE), HQ dipeptide (HQ), RS dipeptide (RS), HP dipeptide (HP), carnosine (AH), tipeptide-1 (GHK), tripepdide-3 (G
- the peptide-fatty acid conjugate is palmitoyl dipeptide-6 (KV), palmitoyl dipeptide-7 (KT), palmitoyl carnosine (AH), azelaoyl tripeptide-1 (GHK), palmitoyl-tripeptide-3 (GHR), myristoyl tripeptide-5 (KVK), palmitoyl tripeptide-1 (GHK), palmitoyl tripeptide-5 (KVK), palmitoyl tripeptide (RFK), myristoyl tripeptide-1 (GHK), palmitoyl tripeptide-4 (LGD), palmitoyl tripeptide-8 ( HFR), palmitoyl tetrapeptide-7 (GQPR), myristoyl pentapeptide-17 (KLAKK), palmitoyl pentapeptide-4 (KTTKS), palmitoyl pentapeptide-17 (KLAKK), myristoyl hexapeptide-12 (VGVAPG) and palmitoyl dipeptide
- the novel metal layered hydroxide composite in the present invention can be applied to cosmetics, detergents, pharmaceuticals, etc. depending on the composition of the active ingredient and the surface modifier.
- the functionality of the prepared material may be diversified according to the characteristics of the anion used as an active ingredient and/or a surface modifier. Specifically, it is characterized by a cosmetic that has increased absorption when applied to the skin after manufacture using ascorbic acid as the active ingredient and a surface modifier, or ascorbic acid as the active ingredient, and a surface modifier as an interface. When applied as an active agent, it plays a role as a detergent with antioxidant efficacy.
- the metal layered hydroxide composite of the present invention may be used for cosmetics or pharmaceutical compositions.
- the pharmaceutical composition comprising the metal layered hydroxide complex of the present invention may additionally contain an appropriate carrier, excipient, or diluent according to a conventional method.
- Carriers, excipients, and diluents that may be included in the pharmaceutical composition containing the compound include lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, gum acacia, alginate, gelatin, calcium phosphate, calcium Silicate, cellulose, methyl cellulose, microcrystalline cellulose, polyvinyl pyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate, and mineral oil, but are not limited thereto.
- the pharmaceutical composition of the present invention is any one selected from the group consisting of powders, pills, granules, capsules, suspensions, liquid solutions, emulsions, syrups, sterilized aqueous solutions, non-aqueous solutions, freeze-dried agents, and suppositories according to a conventional method. It can be formulated in the formulation of. When formulating the pharmaceutical composition of the present invention, it can be prepared using diluents or excipients such as generally used fillers, extenders, binders, wetting agents, disintegrants, and surfactants.
- Solid preparations for oral administration include tablets, pills, powders, granules, capsules, and the like, and these solid preparations include at least one excipient, for example, starch, calcium carbonate, sucrose or It can be prepared by mixing lactose, gelatin, and the like.
- excipients for example, starch, calcium carbonate, sucrose or It can be prepared by mixing lactose, gelatin, and the like.
- lubricants such as magnesium stearate and talc are also used.
- Liquid preparations for oral use include suspensions, liquid solutions, emulsions, syrups, etc.
- various excipients such as wetting agents, sweetening agents, fragrances, and preservatives may be included. .
- Formulations for parenteral administration include sterile aqueous solutions, non-aqueous solvents, suspensions, emulsions, lyophilized formulations, and suppositories.
- non-aqueous solvent and suspending agent propylene glycol, polyethylene glycol, vegetable oil such as olive oil, and injectable ester such as ethyl oleate may be used.
- injectable ester such as ethyl oleate
- a base for suppositories witepsol, macrogol, tween 60, cacao butter, laurin paper, glycero gelatin, and the like may be used.
- the pharmaceutical composition containing the metal layered hydroxide complex of the present invention can be administered orally or parenterally (for example, intravenous, subcutaneous, intraperitoneal or topical application) according to a desired method, and the dosage is the patient's health condition.
- Weight, age, sex, diet, excretion rate, degree of disease, drug type, administration time, administration route and administration period vary depending on the range, but may be appropriately selected by those skilled in the art. It is not intended to limit the scope of the invention in any way.
- the term for cosmetic or pharmaceutical compositions in the present invention may be specifically a skin external formulation, and more specifically, the skin external formulation is a solution, suspension, emulsion, paste, gel, cream, lotion, powder, soap, surfactant -It may be formulated into any one selected from the group including cleansing, oil, powder foundation, emulsion foundation, wax foundation, and spray, but if it is a formulation used for skin application, it is not limited thereto.
- the skin external formulation is a solution, suspension, emulsion, paste, gel, cream, lotion, powder, soap, surfactant -It may be formulated into any one selected from the group including cleansing, oil, powder foundation, emulsion foundation, wax foundation, and spray, but if it is a formulation used for skin application, it is not limited thereto.
- the metal layered hydroxide composite of the present invention may be manufactured by an outer ion-exchange method or a crossover interposition method, but is not limited thereto.
- the particle size can be adjusted and the dispersibility can be excellent.
- the above method was conceived from the method of surface modification by growing the particle size to the maximum by maximizing the aggregation growth time of the seed generated by the nucleation after the start of synthesis.
- the particle size is small and the surface area between particles is high, so the surface treatment is very useful. It is preferable in Modification of the particle surface depends on the pKa that is most active in the aqueous solution state, depending on the functional group (functional group: hydroxy group (-OH), carbonyl group of ketone (-CO-), formyl group of aldehyde (-CHO), organic acid. It is prepared by using the properties of anionic substances having a carboxyl group (-COOH), an amino group (-NH2) for an amine, sulfates, phosphates, etc.).
- the precursor of the metal layered hydroxide complex is specifically ZnO, ZnSO 4 , ZnCl 2 , ZnCO 3 , Zn(NO 3 )-6H 2 O, Zn(CH 3 COO) 2 , CaO, CaCl 2 , Ca(NO 3 ) 2 6H 2 O, CaSO 4 , CaCO 3 , Ca(OH) 2 , MgO, MgCl 2 , MgSO 4 , Mg(NO 3 ) 2 6H 2 O, CuO, Cu(NO 3 ) 2 6H 2 O, CuCl 2 , CuSO 4 , Co(NO 3 ) 2 , CoCO 3 , CoCl 2 , Co(OH) 2 , CoSO 4 , Co(CH 3 COO) 2 , NiO, NiCl 2 , Ni(NO 3 ) 2 , NiSO 4 , It can be NiCO 3 , Ni(OH) 2 , FeO, FeCl 3 , Fe(NO 3 ) 3 , It can be
- the outer ion-exchange method includes the steps of preparing a solution in which the precursor is dissolved by dropping and dissolving an acidic solution to the precursor of the metal layered hydroxide complex; Preparing crystal nuclei containing an active ingredient by mixing alcohol, distilled water, an active ingredient, and the like in a solution in which the precursor is dissolved; And an ion exchange step of ion exchange by mixing a surface modifier with the prepared crystal nuclei. More specifically, the outer ion-exchange method maximizes the aggregation growth time of the nuclear particles bound to the active ingredient to increase the size of the crystal for a certain period of time, and uses a surface modifier in the step prior to cleaning.
- the pH of the ion exchange step is 5 or more and 10 or less, the release of the active ingredient according to the pH change can be minimized by maintaining the synthesis pH condition of the existing metal layered hydroxide, and the sustained release of the active ingredient by preventing the collapse of the metal layered hydroxide structure. It is desirable in that it has the advantage of increasing the performance.
- a peptide having a PI value of 5 to 10 corresponding to a condition of pH 5 or more and 10 or less may be more preferable.
- the PI (Isoelectric Point) value refers to the electrostatic properties of the peptide and refers to the average value expressed by the electrostatic characteristics of the dipolar structure of pKa of the peptide. There is a close relationship with the pKa of the peptide.
- the ratio of the active ingredient and the surface modifier may be in a molar ratio of 1:0.0005 to 0.0005:1. If the above range is satisfied, it is preferable in that the sustained release of the active ingredient can be effectively controlled, the particle size of the metal layered hydroxide can be reduced, and the amount of unnecessary coating agents can be reduced. More specifically, the ion exchange step is characterized in that the surface is modified using anion exchange capacity.
- the external ion exchange method may be manufactured to form a structure in which the outermost shell of the metal layered hydroxide composite is surrounded by a surface modifier layer (see FIGS. 1 and 2).
- the crossover insertion method comprises the steps of preparing a solution in which the precursor is dissolved by dropping and dissolving an acidic solution to the precursor of the metal layered hydroxide composite; And preparing a metal layered hydroxide composite by mixing alcohol, distilled water, an active ingredient, a surface modifier, and the like in a solution in which the precursor is dissolved.
- the ratio of the active ingredient and the surface modifier may be 0.9995:0.0005 to 0.0005:0.9995 in molar ratio.
- the crossover insertion method may be prepared so as to form a structure in which an active ingredient and a surface modifier are mixed inside and outside the metal layered hydroxide composite. (See Fig. 2)
- the surface modifiers used in the present invention are SMA 1: pentapeptide-4, SMA2: palmitoyl dipeptide-7.
- the experiment is carried out in the order of synthesis-washing-drying as follows.
- the conc. HCl solution is slowly added dropwise to the main tank, titrated to a pH of 0.5 to 1, and dissolved by stirring at 700 rpm for 30 minutes under a nitrogen atmosphere.
- the separated precipitate is diluted with ethanol and tertiary distilled water in a volume ratio of 1: 9 to 9: 1 in a nitrogen atmosphere and stirred at 700 rpm for 30 minutes.
- SMA is dissolved in ethanol (50%) by adjusting the molar ratio of 1: 0.05, 1: 0.025, 1: 0.005, 1: 0.0025, 1: 0.0005 relative to the amount of AA input to the dispersed precipitate solution, and then very slowly added to the slightly alkaline solution. Keep the pH 6 ⁇ 8 and stir for 1 ⁇ 3 hours. After the reaction was completed, the precipitate was centrifuged at 8000 rpm.
- the precipitate was evenly diluted in a 1:1 ratio of ethanol and tertiary distilled water, and then proceeded at 8000 rpm for 5 minutes. Repeat this process 3 times. The last centrifugal washing is diluted with ethanol only, and then centrifuged at 9000 rpm for 10 minutes to obtain a precipitate. The washed precipitate solution was spray-dried while stirring at 600 rpm to make powder.
- the surface modifier used in the present invention is SMA 1: pentapeptide-4.
- SMA2 palmitoyl dipeptide-7.
- the experiment is carried out in the order of synthesis-washing-drying as follows. After adding the weight equivalent to ZnO 2.5equiv. to the main tank, conc. HCl solution is slowly added dropwise and titrated to a pH of 0.5 to 1, and dissolved while stirring at 700 rpm for 30 minutes under a nitrogen atmosphere. After that, add AA 1equiv. and SMA 1 equiv. of auxiliary tank 2, 3rd distilled water, and ethanol (total amount of solvent is 20 volume compared to Zn), and stir for 10 minutes at 300 rpm to dissolve.
- a metal layered hydroxide composite was prepared in the same manner as in Preparation Example 1 except that the content was changed according to Tables 1 and 2 below.
- a metal layered hydroxide composite was prepared in the same manner as in Preparation Example 2 except that the content was changed according to Tables 3 and 4 below.
- the X-ray diffractometer was measured using D/MAXPRINT 2200-Ultima from Rigaku (Japan).
- the tube voltage was 40kV and a current of 30mA was applied.
- the one-dimensional (1D) electron density for the z axis is calculated by the following equation.
- the powder obtained through the synthesis was compared and analyzed through an XRD diffraction pattern, and the interlayer distance accordingly was calculated through Bragg's equation (Equation 2 below).
- the interlayer distance including the distance between the layer of the synthesized metal layered hydroxide and the layer with anions, can be called the main interlayer distance.
- Example 1 is labeled as sample 1
- Example 3 is sample 2
- Example 5 is sample 3
- Example 5 is sample 3
- Example 15 is marked as sample 3 and specific values are described in Tables 5 and 6, respectively. (See Figures 5 and 6)
- Example 6 is represented as sample(1), Example 8 as sample (2), Example 10 as sample (3), and Example 16 in Table 8 and FIG. 1), Example 18 was denoted as sample (2), and Example 20 as sample (3), and specific values were described in Tables 7 and 8, respectively. (See Figs. 7 and 8)
- the ⁇ (theta) value of the main peak of each sample is 5.9, 5.92, 5.94 for SMA1.
- SMA2 it was confirmed that it was 6.04, 6.06, and 5.96, and the d-value (interlayer distance) value was 14.97, 14.92, and 14.86 ⁇ in the case of SMA1, and it was confirmed that the d-value (interlayer distance) was almost unchanged to 14.62, 14.57 and 14.81 ⁇ in the case of SMA2.
- Comparative Example 5 is labeled as sample 1
- Example 21 as sample 2
- Example 22 as sample 3 and Example 23 as sample 4
- Comparative Example 7 is sample 1
- Example 28 is sample 2
- Example 29 as sample 3
- Example 30 as sample 4
- specific values are described in Tables 9 and 10, respectively.
- ⁇ max was measured at 240 nm and measured with a Zorbax C18 column (4.6mm x 150mm, 5 ⁇ m, Agilent Technologies, USA) at 0.65mL/min, injection volume 10 ⁇ l, and column temperature 35°C.
- the mobile phase buffer contains 0.1% of Trifluoroacetic acid (ReagentPlus®, 99%), and a solution prepared in a 2:8 volume ratio of acetonitrile (anhydrous, 99.8%) and tertiary distilled water is used.
- sample processing 40 mg of sample is mixed with 100 mL of the buffer solvent, sonicated for 10 minutes, and then stirred rapidly for 10 minutes. Samples were measured by filtering this solution using a nylon syringe filter (pore size 0.2 ⁇ m).
- the mobile phase buffer contains 0.1% of Trifluoroacetic acid (ReagentPlus®, 99%), and a solution prepared in a 5:5 volume ratio of acetonitrile (anhydrous, 99.8%) and tertiary distilled water is used.
- sample 50 mg of the sample is mixed with 100 mL of the buffer solvent, sonicated for 10 minutes, and then rapidly stirred for 10 minutes. Samples were measured by filtering this solution using a nylon syringe filter (pore size 0.2 ⁇ m).
- the Tindall effect is an optical property of colloidal solutions.
- the colloidal solution particles have a particle size of 1 nm to 1000 nm, and are not mutually agglomerated and stabilized by the Van der Waals attractions and electrostatic repulsion of the particles.
- Colloidal particles move at a high speed in a dispersion medium, which is known as Brownian motion, and because the size of colloidal particles is similar to or larger than the wavelength of light, it cannot reflect light, but light scattering occurs. Therefore, the Tindall effect is a phenomenon that appears as light scattering by colloidal particles.
- Tindal phenomenon 50 mg of each powder was put in a petri dish, put into a vial containing 50 ml of 3rd distilled water, and dispersed evenly for 10 minutes using a stirrer. All dispersion systems were set to 1000 ppm.
- the solution was allowed to stand for 30 minutes, and the light was transmitted through a laser pointer beam to observe the Tindall effect.
- the effect is described by dividing it into cases where the transmission, particle size is 1 ⁇ m or more, and precipitation occurs.
- the Tindall effect on the metal layered hydroxide prepared in Examples 1 to 5 and Comparative Example 1 is shown in Figs. 11 to 13, and the Tindall effect on the metal layered hydroxide prepared in Examples 11 to 15 and Comparative Example 2 is shown in Figs. 14 to 16. Each is described in.
- the particle size of the powder was measured by Malvern PanalyticalT's (UK) Zetasizer using electrophoretic light scattering, and the particle size was measured after dispersing the sample in tertiary distilled water using the model name NANO ZS ZS90.
- the surface potential of the molecule was measured by Malvern PanalyticalT's (UK) Zetasizer using electrophoretic light scattering, and the surface potential was measured after dispersing the sample in tertiary distilled water using the model name NANO ZS ZS90.
- the paddle method which is the most commonly used among general test methods in the Korean Pharmacopoeia, was used. Add 300mg of each raw material powder to 300mL of 0.08wt% NaCl tertiary distilled water aqueous solution (or a solution containing 0.08wt% NaCl and 10% ethanol) and disperse it, and induce the release of the measured component while stirring at 25°C and 50rpm. Then, the solution was taken every predetermined time, filtered through a nylon syringe filter (pore size 0.2 ⁇ m), and measured using HPLC.
- sustained-release property of ascorbic acid increased according to the ratio of the surface modifier in each of the examples. Depending on the ratio of the surface modifier, it was confirmed that the sustained-release property increased from about 53% to the maximum of about 68% for 72 hours, and the longer the storage period, the more excellent the sustained-release property of the surface modifier was lower than ascorbic acid. It was confirmed that it can be.
- sustained-release property of ascorbic acid increased according to the ratio of the surface modifier in each of the examples. Depending on the ratio of the surface modifier, it was confirmed that the sustained-release property increases from about 49% to the maximum for 72 hours for 72 hours, and the longer the storage period, the better the sustained-release property of the crystallinity lower than that of ascorbic acid. It was confirmed that it can be.
- sustained-release property of ascorbic acid increased according to the ratio of the surface modifier in each of the examples. Depending on the ratio of the surface modifier, it was confirmed that the sustained-release property increased from about 40% to the maximum of about 57% for 72 hours, and the longer the storage period, the better the sustained-release property of the surface modifier with lower crystallinity compared to ascorbic acid. It was confirmed that it can be.
- sustained-release property of ascorbic acid increased according to the ratio of the surface modifier in each of the examples. Depending on the ratio of the surface modifier, it was confirmed that the sustained-release property increased from about 39% to the maximum of about 58% for 72 hours, and the longer the storage period, the more excellent the sustained-release property of the surface modifier was lower than ascorbic acid. It was confirmed that it can be.
- the particle size was measured to be 3 ⁇ m (3000nm) or more overall, but this particle size appears larger than the particle size of our invention.
- the zeta potential is negative overall, which is a result of the coating agent used.
- the relatively small particle size can be more effective in skin absorption.
- the present invention provides a metal layered hydroxide composite having an excellent sustained release effect by including an active ingredient and a surface modifier in the metal layered hydroxide composite, and having a reduced particle size while containing the active ingredient in a stable state in the metal layered hydroxide composite.
- it is possible to easily synthesize an effective material having an opposite charge with the metal layered hydroxide by electrostatic attraction or to control the crystallinity of the metal layered hydroxide, so the processing time is short and special manufacturing facilities are required. It is not eco-friendly and can provide economical effects.
- the present invention provides a method for producing a metal layered hydroxide having a safe effect by not using harmful substances, since post-treatment such as a cleaning process due to the use of an organic solvent is not required.
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Epidemiology (AREA)
- Birds (AREA)
- Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Inorganic Chemistry (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Dermatology (AREA)
- Physics & Mathematics (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Geometry (AREA)
- Emergency Medicine (AREA)
- Biomedical Technology (AREA)
- Optics & Photonics (AREA)
- Nanotechnology (AREA)
- Ceramic Engineering (AREA)
- Gerontology & Geriatric Medicine (AREA)
- Cosmetics (AREA)
- Medicinal Preparation (AREA)
Abstract
Description
Claims (9)
- 활성성분; 및 표면개질제를 포함하는 금속 층상수산화물 복합체로써,상기 활성성분은 아스코브산(ascorbic acid), 비오틴(biotine), 판테토산(pantothenic acid), 시스테인(cysteine), 페룰릴산(ferulic acid), 글루탐산(glutamic acid), 인돌 아세틱산(indole acetic acid), 시나믹산(cinnamic acid), 카페익산(caffeic acid), 티아민(thiamine), 리보플라빈(riboflavin), 나이아신(niacin), 판토텐산(pantothenic acid), 피리독신(pyridoxine), 폴산(folic acid), 칼시페롤(calciferol), 토코페롤(tocopherol), 트라넥사민산(Tranexamic acid), 살리실산(salicylic acid), 레티노산(retinoic acid) 및 알부틴(arbutin)으로 이루어진 군으로부터 선택되는 1종이상이며,상기 표면 개질제는 2 내지 8개의 아미노산을 포함하는 펩타이드; 및 2 내지 8개의 아미노산을 포함하는 펩타이드 와 탄소수 10 내지 16의 지방산을 포함하는 펩타이드-지방산 결합체로 이루어진 군으로부터 선택되는 1종 이상을 포함하는 금속 층상수산화물 복합체.
- 청구항 1에 있어서, 상기 펩타이드는 dipeptide-1 (YR), dipeptide-2 (VW), dipeptide-4 (FW), dipeptide-6 (KV), dipeptide-7(KT), dipeptide-14 (AT), dipeptide (GH), acetyl dipeptide-1 (YR), acetyl dipeptide-1 cetyl Ester (YR), nicotinoyl dipeptide-2 (VW), CP dipeptide (CP), VGE dipeptide (VE), CGE dipeptide (CE), EGE dipeptide (EE), TGE dipeptide (TE), LGE dipeptide (LE), EQ dipeptide (EQ), GR dipeptide (GR), HG dipeptide (HG), PE dipeptide (PE), DE dipeptide (DE), HQ dipeptide (HQ), RS dipeptide (RS), HP dipeptide (HP), carnosine (AH), tipeptide-1 (GHK), tripepdide-3 (GHR), tripeptide-4 (LGD), tripepdie-5 (KVK), tripeptide-6 (GXP), tripeptide-8 (HFR), tripeptide-10 (KDI), RGD peptide (RGD), AHK peptide (AHK), tripeptide-29 (GPX), tripeptide-54 (FTY), biotinoyl tripeptide-1 (GHK), thioctoyl tripeptide-1 (GHK), tripeptide (RFK), HGG peptide (HGG), peptide CK (RKR), tetrapeptide-1 (LPTV), tetrapeptide-2 (KDVY), tetrapeptide-3 (KGHK), tetrapeptide-5 (AHSH), tetrapeptide-7 (GQPR), tetrapeptide-9(QDVH), tetrapeptide-11(PPYL), tetrapeptide-15 (YPFF), tetrapeptide-21(GEKG), tetrapeptide-26(ELPS), acetyl tetrapeptide-2 (KDVY), acetyl tetrapeptide-3 (KGHK), acetyl tetrapeptide-5 (AHSH), acetyl tetrapeptide-9 (QDVH), acetyl tetrapeptide-11 (PPYL), acetyl tetrapeptide-15 (YPFF), pentapeptide-3(GPRPA), pentapeptide-4 (KTTKS), pentapeptide-17 (KLAKK), pentapeptide-18 (YAGFL), thioctoyl pentapeptide-4 (KTTKS), hexapeptide-1 (ARHLFW), hexapeptide-2 (FWFKPV), hexapeptide-3 (EEMQRR), hexapeptide-4 (FGHXAF), hexapeptide-5 (FGVXAF), hexapeptide-6 (VEPIPY), hexapeptide-9 (GPQGPQ), hexapeptide-11 (FVAPFP), hexapeptide-12 (VGVAPG), acetyl hexapeptide-1 (ARHLFW), acetyl hexapeptide-3 (EEMQRR), acetyl hexapeptide-6 (VEPIPY), heptapeptide-1 (EDDDWDF), heptapeptide-7 (MGRNIRN), cysteine peptide (RFAACAA), lysine peptide (RFAAKAA), selank (TKPRPGP), octapeptide-2 (TAEEHEVM), octapeptide-3 (EEMQRRAD), octapeptide-4 (YGGFLGHK) 및 acetyl octapeptide-3 (EEMQRRAD)으로 이루어진 군으로부터 선택되는 1종 이상인, 금속 층상수산화물 복합체.
- 청구항 1에 있어서, 상기 펩타이드-지방산 결합체는 palmitoyl dipeptide-6 (KV), palmitoyl dipeptide-7 (KT), palmitoyl carnosine (AH), azelaoyl tripeptide-1 (GHK), palmitoyl-tripeptide-3 (GHR), myristoyl tripeptide-5 (KVK), palmitoyl tripeptide-1 (GHK), palmitoyl tripeptide-5 (KVK), palmitoyl tripeptide (RFK), myristoyl tripeptide-1 (GHK), palmitoyl tripeptide-4 (LGD), palmitoyl tripeptide-8 (HFR), palmitoyl tetrapeptide-7 (GQPR), myristoyl pentapeptide-17 (KLAKK), palmitoyl pentapeptide-4 (KTTKS), palmitoyl pentapeptide-17 (KLAKK), myristoyl hexapeptide-12 (VGVAPG) 및 palmitoyl hexapeptide-12 (VGVAPG)으로 이루어진 군으로부터 선택되는 1종 이상인, 금속 층상수산화물 복합체.
- 청구항 1에 있어서, 금속 층상수산화물 복합체는 외부 이온 교환법(outer ion-exchange) 또는 크로스오버 삽입법(crossover interposition)으로 제조되는 것인, 금속 층상수산화물 복합체.
- 청구항 4에 있어서, 상기 외부 이온 교환법은 금속 층상수산화물 복합체의 최외각이 표면 개질제층으로 둘러쌓인 구조를 형성하도록 제조되는 것인, 금속 층상수산화물 복합체.
- 청구항 4에 있어서, 상기 크로스오버 삽입법은 활성성분 및 표면개질제가 금속 층상수산화물 복합체의 내부 및 최외각에 혼합되어 있는 구조를 형성하도록 제조되는 것인, 금속 층상수산화물 복합체.
- 청구항 1에 있어서, 상기 금속 층상수산화물 복합체는 72간 이내 활성성분 방출율이 65%이하의 서방성을 갖는, 금속 층상 수산화물 복합체.
- 금속 층상수산화물 복합체의 전구체에 산성 용액을 적가하여 용해시켜 전구체가 용해된 용액을 제조하는 단계; 및 상기 전구체가 용해된 용액에 알코올, 증류수, 활성성분 및 표면개질제를 혼합하여 금속 층상수산화물 복합체를 제조하는 단계를 포함하는 것인, 청구항 1의 금속 층상수산화물 복합체의 제조방법.
- 금속 층상수산화물 복합체의 전구체에 산성 용액을 적가하여 용해시켜 전구체가 용해된 용액을 제조하는 단계; 상기 전구체가 용해된 용액에 알코올, 증류수 및 활성성분 혼합하여 활성성분 포함하는 결정핵을 제조하는 단계; 및 상기 제조된 결정핵에 표면 개질제를 혼합하여 이온교환 시키는 금속 층상 수산화물 복합체를 제조하는 이온교환 단계를 포함하며, 상기 이온교환 단계의 pH가 5이상 내지 10 이하인, 청구항 1의 금속 층상수산화물 복합체의 제조방법.
Priority Applications (5)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
EP20763976.6A EP3760183A4 (en) | 2019-05-03 | 2020-04-29 | NEW LAMINATED METAL HYDROXIDE COMPOSITE AND METHOD FOR PREPARING IT |
JP2020573419A JP2022530173A (ja) | 2019-05-03 | 2020-04-29 | 新規金属層状水酸化物錯体およびその調製方法 |
CN202080001919.6A CN112188883A (zh) | 2019-05-03 | 2020-04-29 | 新型金属层状氢氧化物复合物及其制备方法 |
AU2020269033A AU2020269033A1 (en) | 2019-05-03 | 2020-04-29 | Novel metal layered hydroxide composite and preparation method therefor |
US16/969,754 US20210236406A1 (en) | 2019-05-03 | 2020-04-29 | Novel metal layered hydroxide complex and method of preparing same |
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
KR1020190052504A KR102120992B1 (ko) | 2019-05-03 | 2019-05-03 | 신규한 금속 층상수산화물 복합체 및 이의 제조방법 |
KR10-2019-0052504 | 2019-05-03 |
Publications (1)
Publication Number | Publication Date |
---|---|
WO2020226348A1 true WO2020226348A1 (ko) | 2020-11-12 |
Family
ID=71087090
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/KR2020/005706 WO2020226348A1 (ko) | 2019-05-03 | 2020-04-29 | 신규한 금속 층상수산화물 복합체 및 이의 제조방법 |
Country Status (7)
Country | Link |
---|---|
US (1) | US20210236406A1 (ko) |
EP (1) | EP3760183A4 (ko) |
JP (1) | JP2022530173A (ko) |
KR (1) | KR102120992B1 (ko) |
CN (1) | CN112188883A (ko) |
AU (1) | AU2020269033A1 (ko) |
WO (1) | WO2020226348A1 (ko) |
Families Citing this family (7)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US11951203B2 (en) * | 2020-08-26 | 2024-04-09 | Chanda Zaveri | Deep wrinkle vanishing compositions |
WO2022083996A1 (en) | 2020-10-22 | 2022-04-28 | Unilever Ip Holdings B.V. | An oral care composition for whitening benefits |
CN112516006A (zh) * | 2020-12-10 | 2021-03-19 | 武汉百思凯瑞生物科技有限公司 | 一种具有防脱生发、固发、黑发功能的纳米组合物及其制备方法和应用 |
CN113004370B (zh) * | 2021-02-09 | 2022-06-17 | 宁波绿之健药业有限公司 | 一种具有缓解高尿酸血症和调节肠道菌群的二肽及其应用 |
CN113578215A (zh) * | 2021-08-03 | 2021-11-02 | 安徽农业大学 | 一种硒-金复合纳米材料及其制备方法 |
CN115010784B (zh) * | 2022-05-16 | 2023-03-31 | 江南大学 | 一种ace抑制肽及其应用 |
CN115144508B (zh) * | 2022-09-02 | 2022-12-13 | 广州市乾相生物科技有限公司 | 一种适用于多种水溶性肽的hplc分离方法 |
Citations (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
KR100439299B1 (ko) | 2001-07-28 | 2004-07-07 | (주)나노하이브리드 | 개선된 특성을 갖는 화장품 원료 물질 및 그 제조 방법 |
JP2005238194A (ja) * | 2004-02-27 | 2005-09-08 | National Institute Of Advanced Industrial & Technology | コロイド粒子化水酸化物系樹脂配合剤およびそれを含有する樹脂組成物 |
KR20060094745A (ko) * | 2005-02-25 | 2006-08-30 | (주)나노하이브리드 | 층상형 금속 수산화물과 레티노익산의 혼성체를 함유하는암치료용 약학적 조성물 |
KR20060132409A (ko) | 2005-06-18 | 2006-12-21 | (주)나노하이브리드 | 비타민 c와 층상 금속 수산화물 또는 금속 산화물의혼성체를 이용한 제빵 개량제 및 이의 제조 방법 |
KR20180021283A (ko) * | 2016-08-18 | 2018-03-02 | (주) 에이치엔에이파마켐 | 나노에멀젼 및 개질된 층상 이중 수산화물을 포함하는 경피 전달용 조성물 |
Family Cites Families (10)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5538945A (en) * | 1994-06-17 | 1996-07-23 | Procyte Corporation | Stimulation of hair growth by peptide copper complexes |
KR100443892B1 (ko) * | 2001-08-02 | 2004-08-09 | (주)나노하이브리드 | 비타민 함유 무기 하이브리드 및 그의 제조방법 |
CN101855235B (zh) * | 2007-10-29 | 2013-04-24 | 赫里克斯生物医疗公司 | 保护性皮肤护理四肽 |
KR101082391B1 (ko) * | 2009-01-23 | 2011-11-11 | (주)씨앤팜 | 비타민 c를 포함하는 탈모 방지 및 발모 촉진용 나노하이브리드 복합체 및 발모 촉진용 조성물 |
KR101118691B1 (ko) * | 2009-09-14 | 2012-03-12 | (주)씨앤팜 | 표적지향성 siRNA-층상형 무기 수산화물 나노혼성체, 그 제조방법, 및 나노혼성체를 함유하는 종양 치료용 약학 조성물 |
CN102302926A (zh) * | 2011-06-21 | 2012-01-04 | 长治学院 | 一种复合改性层状双金属氢氧化物及其制备方法 |
CN104203230A (zh) * | 2011-09-23 | 2014-12-10 | 埃米·纽伯格 | 抗拉伸纹皮肤乳膏及其制造和使用方法 |
CN102641507B (zh) * | 2012-05-15 | 2013-05-15 | 山东炳坤腾泰陶瓷科技有限公司 | 一种甲氨蝶呤/层状双金属氢氧化物纳米复合材料的制备方法 |
US10272057B2 (en) * | 2012-10-05 | 2019-04-30 | Oxford Pharmascience Limited | Layered double hydroxides |
KR101704212B1 (ko) * | 2015-06-12 | 2017-02-08 | 씨제이제일제당 (주) | 젖산을 생산하는 미생물 및 이를 이용한 젖산 제조 방법 |
-
2019
- 2019-05-03 KR KR1020190052504A patent/KR102120992B1/ko active IP Right Grant
-
2020
- 2020-04-29 CN CN202080001919.6A patent/CN112188883A/zh active Pending
- 2020-04-29 WO PCT/KR2020/005706 patent/WO2020226348A1/ko unknown
- 2020-04-29 EP EP20763976.6A patent/EP3760183A4/en active Pending
- 2020-04-29 AU AU2020269033A patent/AU2020269033A1/en not_active Abandoned
- 2020-04-29 US US16/969,754 patent/US20210236406A1/en not_active Abandoned
- 2020-04-29 JP JP2020573419A patent/JP2022530173A/ja active Pending
Patent Citations (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
KR100439299B1 (ko) | 2001-07-28 | 2004-07-07 | (주)나노하이브리드 | 개선된 특성을 갖는 화장품 원료 물질 및 그 제조 방법 |
KR100841700B1 (ko) | 2001-07-28 | 2008-06-26 | (주)나노하이브리드 | 개선된 특성을 갖는 화장품 원료 물질 및 그 제조 방법 |
JP2005238194A (ja) * | 2004-02-27 | 2005-09-08 | National Institute Of Advanced Industrial & Technology | コロイド粒子化水酸化物系樹脂配合剤およびそれを含有する樹脂組成物 |
KR20060094745A (ko) * | 2005-02-25 | 2006-08-30 | (주)나노하이브리드 | 층상형 금속 수산화물과 레티노익산의 혼성체를 함유하는암치료용 약학적 조성물 |
KR20060132409A (ko) | 2005-06-18 | 2006-12-21 | (주)나노하이브리드 | 비타민 c와 층상 금속 수산화물 또는 금속 산화물의혼성체를 이용한 제빵 개량제 및 이의 제조 방법 |
KR20180021283A (ko) * | 2016-08-18 | 2018-03-02 | (주) 에이치엔에이파마켐 | 나노에멀젼 및 개질된 층상 이중 수산화물을 포함하는 경피 전달용 조성물 |
Non-Patent Citations (1)
Title |
---|
See also references of EP3760183A4 |
Also Published As
Publication number | Publication date |
---|---|
JP2022530173A (ja) | 2022-06-28 |
AU2020269033A1 (en) | 2021-02-25 |
EP3760183A4 (en) | 2022-02-23 |
EP3760183A1 (en) | 2021-01-06 |
US20210236406A1 (en) | 2021-08-05 |
KR102120992B1 (ko) | 2020-06-10 |
CN112188883A (zh) | 2021-01-05 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
WO2020226348A1 (ko) | 신규한 금속 층상수산화물 복합체 및 이의 제조방법 | |
WO2011021804A2 (ko) | 감응성 고분자 캡슐 및 그 제조방법 | |
WO2018128360A1 (ko) | 암 및 피부질환 치료를 위한 생체 적합성 광열용 조성물 | |
WO2015037891A1 (ko) | 신규 고리형 화합물을 함유하는 피부미백제 | |
WO2023014006A1 (ko) | Ras의 표적 분해를 위한 화합물 | |
WO2020222461A1 (ko) | 면역항암 보조제 | |
WO2021194298A1 (ko) | 약물 이합체를 포함하는 나노입자 및 이의 용도 | |
WO2017090873A1 (ko) | 양친성 고분자 | |
WO2020222541A1 (ko) | 캐스파제 저해제의 프로드럭 | |
WO2019168357A1 (en) | Water soluble salts of lipidated peptides and methods for preparing and using the same | |
WO2011132901A2 (en) | Novel benzamide derivatives | |
EP2247644A2 (en) | Ph-sensitive polyethylene oxide co-polymer and synthetic method thereof | |
WO2010110622A2 (en) | Novel crystal forms of adefovir dipivoxil and processes for preparing the same | |
WO2012070700A1 (ko) | 퀴놀린 유도체 화합물, 이의 제조방법 및 이를 포함하는 약학 조성물 | |
WO2022220519A1 (ko) | 5-[(1,1-디옥시도-4-티오몰포리닐)메틸]-2-페닐-n-(테트라하이드로-2h-피란-4-일)-1h-인돌-7-아민의 신규 결정형 | |
WO2013002592A2 (ko) | 베툴론산의 고순도 정제방법, 고순도 베툴론산을 이용한 피페라진 베툴론산 아마이드 유도체의 제조방법과 그 유도체, 고순도 베툴론산을 이용한 고순도 비오씨-라이시네이티드 베툴론산 정제방법 | |
WO2011014009A2 (ko) | 신규 이치환된 페녹시아세틸계 화합물 또는 이의 약학적으로 허용가능한 염, 이의 제조방법 및 이를 유효성분으로 함유하는 다약제내성 억제용 약학적 조성물 | |
WO2015115796A1 (ko) | 페길레이션된 7-디하이드로콜레스테롤 유도체 | |
WO2021145586A1 (ko) | 국소 지방 감소용 기체 발포형 마이셀 | |
WO2020162723A1 (ko) | 금속-유기 단위체를 포함하는 다공성 액체 조성물, 다공성 고분자 조성물 및 이들의 제조방법 | |
WO2019132610A1 (ko) | Baf57 재조합 융합 단백질 및 이의 용도 | |
WO2020209475A1 (ko) | 점토광물 복합체를 포함하는 방출성이 제어된 경구투여용 조성물, 그 제조 방법 및 방출성 제어방법 | |
WO2021029450A1 (ko) | 신규한 피리미딘 설폰아마이드 유도체 및 이를 유효성분으로 포함하는 암 예방 또는 치료용 약학 조성물 | |
WO2022220518A1 (ko) | 5-[(1,1-디옥시도-4-티오몰포리닐)메틸]-2-페닐-n-(테트라하이드로-2h-피란-4-일)-1h-인돌-7-아민 황산염 및 이의 신규 결정형 | |
WO2021194291A1 (ko) | (-)-시벤졸린 숙신산염의 결정다형 |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
ENP | Entry into the national phase |
Ref document number: 2020763976 Country of ref document: EP Effective date: 20200907 |
|
121 | Ep: the epo has been informed by wipo that ep was designated in this application |
Ref document number: 20763976 Country of ref document: EP Kind code of ref document: A1 |
|
ENP | Entry into the national phase |
Ref document number: 2020573419 Country of ref document: JP Kind code of ref document: A |
|
ENP | Entry into the national phase |
Ref document number: 2020269033 Country of ref document: AU Date of ref document: 20200429 Kind code of ref document: A |
|
NENP | Non-entry into the national phase |
Ref country code: DE |