WO2012074037A1 - 豊胸促進剤 - Google Patents
豊胸促進剤 Download PDFInfo
- Publication number
- WO2012074037A1 WO2012074037A1 PCT/JP2011/077743 JP2011077743W WO2012074037A1 WO 2012074037 A1 WO2012074037 A1 WO 2012074037A1 JP 2011077743 W JP2011077743 W JP 2011077743W WO 2012074037 A1 WO2012074037 A1 WO 2012074037A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- calcium phosphate
- particles
- breast augmentation
- calcium
- fine particles
- Prior art date
Links
Images
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K33/00—Medicinal preparations containing inorganic active ingredients
- A61K33/42—Phosphorus; 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
- A61K8/02—Cosmetics or similar toiletry preparations characterised by special physical form
- A61K8/0241—Containing particulates characterized by their shape and/or 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
- A61K8/24—Phosphorous; Compounds thereof
-
- 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
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- 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
- 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
Definitions
- the present invention relates to a novel breast augmentation promoter.
- breast augmentation methods include, for example, a method of injecting fat into the chest, a method of injecting hyaluronic acid, and a method of placing a bag containing physiological saline, silicon, or the like into the chest.
- Patent Document 1 discloses a skin external composition for breast augmentation containing one or more plant extracts extracted from diam, salamander, shiitake mushroom, salvia, cascon, saicin, tonin, keihi.
- a skin external composition for breast augmentation containing one or more plant extracts extracted from diam, salamander, shiitake mushroom, salvia, cascon, saicin, tonin, keihi.
- fat synthesis is promoted and a breast augmentation effect is obtained.
- Patent Document 2 discloses a breast augmentation composition containing collagen as an active ingredient.
- the composition can be used as a preparation for external use or a supplement, and it is said that it can give a beautiful bust by imparting tension to the bust and can obtain an excellent breast augmentation effect such as an increase in cup size. Yes.
- collagen can enhance the water retention and elasticity of the skin, and at the same time, can achieve skin beautifying effects such as moisturizing the skin.
- the present invention aims to provide a novel breast augmentation promoter.
- the present inventor has found a novel attribute that collagen production is promoted by contact of calcium phosphate microparticles with fibroblasts, and that a breast augmentation effect can be obtained by applying the microparticles to the breast.
- the present invention has been completed by finding the proper attributes.
- the present invention (1) is a breast enlargement promoter characterized by containing calcium phosphate fine particles.
- the present invention (2) is the breast augmentation promoter of the invention (1), wherein the calcium phosphate fine particles are hydroxyapatite fine particles.
- the present invention (3) is the breast enlargement promoter according to the invention (1) or (2), wherein the calcium phosphate fine particles have an average particle diameter of 10 to 1,000 nm.
- the present invention (4) is the breast augmentation promoter according to any one of the inventions (1) to (3), wherein the calcium phosphate fine particles are a sintered body.
- the sintered body is: Mixing the primary particles containing calcium phosphate and the anti-fusing agent; and Exposing the mixed particles obtained by the mixing step to a sintering temperature; and a sintering step;
- the present invention (6) is the breast augmentation promoter according to any one of the inventions (1) to (5), which is for external use.
- the present invention exerts the effect of promoting collagen production by acting on fibroblasts
- applying the present invention to the breast can improve the elasticity of the breast epidermis and the breast, thereby obtaining an effect of promoting breast augmentation.
- it is effective for a chest that has been dripping due to aging or the like, and has an effect of improving the dripping.
- the effect of acting on fibroblasts, particularly promoting collagen production, and obtaining a breast augmentation effect can be obtained.
- the average particle diameter of the calcium phosphate fine particles is very small, an effect of promoting breast augmentation can be obtained by applying to the chest externally.
- the calcium phosphate fine particles are not easily fused to each other even when sintered, and the primary particles are maintained, a sintered body can be obtained with a small particle size. There is an effect that a higher breast augmentation effect can be exhibited.
- FIG. 1 is a graph showing test results using the breast augmentation promoter according to this example.
- FIG. 2 is an echo sectional photograph after applying the breast augmentation agent according to this example to the subject A for 2 months.
- FIG. 3 is an echo sectional photograph after applying the breast augmentation agent according to this example to the subject B for 2 months.
- the breast augmentation agent includes calcium phosphate fine particles.
- Other optional components include breast augmentation active ingredients, alcohols, saccharides, proteins, amino acids, water-soluble vitamins, fat-soluble vitamins, lipids, mucopolysaccharides, and surfactants. It is preferable that
- the calcium phosphate fine particles examples include hydroxyapatite (Ca 10 (PO 4 ) 6 (OH) 2 ), fluoroapatite (Ca 10 (PO 4 ) 6 F 2 ), and Ca 10 (PO 4 ) 6 Cl. 2 etc. are mentioned.
- the calcium phosphate includes calcium ions and / or hydroxide ions and / or phosphate ions, such as strontium ions, barium ions, sodium ions, bicarbonate ions, carbonate ions, fluoride ions, chloride ions, etc.
- a substituted compound, tricalcium phosphate (Ca 3 (PO 4 ) 2 ), calcium metaphosphate (Ca (PO 3 ) 2 ), or calcium octaphosphate (OCP) may be contained.
- hydroxyapatite is preferred.
- the surface of the calcium phosphate particles according to the best mode particles of calcium phosphate
- it is preferable that Ca 10 (PO 4) 6 ( OH) 2 is present.
- This Ca 10 (PO 4 ) 6 (OH) 2 is suitable if it is present on the surface of calcium phosphate, and may be contained in an amount of about 0.1% by weight based on the total amount of calcium phosphate, but 50% by weight. It is more preferable that it is contained above.
- the calcium phosphate fine particles may contain tricalcium phosphate or the like that is produced when amorphous hydroxyapatite is sintered as described later.
- the calcium phosphate according to the present embodiment is excellent in affinity with living tissue and stability in the living environment.
- the average particle diameter of the calcium phosphate fine particles according to the best mode is preferably 10 to 1,000 nm, more preferably 20 to 300 nm, and still more preferably 20 to 250 nm.
- the variation coefficient is preferably 20% or less, more preferably 18% or less, and even more preferably 15% or less.
- the average particle size and coefficient of variation may be calculated by measuring the particle size of at least 100 primary particles using an electron microscope.
- the “variation coefficient” is a value indicating the variation in particle diameter between particles that can be calculated by standard deviation ⁇ average particle diameter ⁇ 100 (%).
- the shape of the calcium phosphate fine particles is not particularly limited, and may be, for example, a particle shape or a rod shape. In the case of a rod shape, the average particle diameter is measured by the major axis of the particle.
- the calcium phosphate fine particles according to the best mode are preferably a calcium phosphate sintered body (also called calcium phosphate ceramics) obtained by sintering (calcining) calcium phosphate.
- a calcium phosphate sintered body also called calcium phosphate ceramics obtained by sintering (calcining) calcium phosphate.
- the calcium phosphate fine particle sintered body By using the calcium phosphate fine particle sintered body, the effect of promoting collagen production is significantly improved as compared with the unsintered one.
- the calcium phosphate fine particle sintered body has higher crystallinity and lower solubility in a living body than amorphous calcium phosphate. Therefore, since the biological activity can be maintained for a long time in the living body, the collagen production promoting effect is easily exhibited for a long time.
- the calcium phosphate fine particle sintered body is obtained by sintering amorphous calcium phosphate.
- a calcium phosphate fine particle sintered body can be obtained by sintering by a method described later. It is also preferable to use highly crystalline calcium phosphate with high crystallinity of the calcium phosphate fine particles.
- the degree of crystallinity of this calcium phosphate can be measured by X-ray diffraction (XRD). Specifically, the narrower the half-value width of the peak indicating each crystal plane, the higher the crystallinity.
- the breast augmentation promoter includes other breast augmentation active ingredients, alcohols, sugars, proteins, amino acids, water-soluble vitamins, fat-soluble vitamins, lipids, mucopolysaccharides, surfactants Is preferably included.
- breast augmentation active ingredients include collagen peptide, Pueraria mifilica root extract, palmitoyl isoleucine, palmitoyl glycine, cocoylalanine Na, palmitoyl dipeptide-5 diaminobutyroylhydroxythreonine alanine, palmitoyl dipeptide-5 diaminohydroxybutyric acid, vorphyrin, It is preferable that isoflavones are contained.
- Examples of alcohols include ethanol and glycerin. By containing alcohols, the dispersion stability of the calcium phosphate fine particles is improved and prompt penetration into the dermis layer is promoted. In addition, it has skin cleaning, astringency, and moisturizing effects.
- Examples of the saccharide include hydrolyzed hydrogenated starch. By containing saccharides, the moisturizing effect and anti-inflammatory effect are improved.
- Examples of proteins include collagen. By including proteins, it becomes a carrier of calcium phosphate and can be promoted to the dermis layer. Examples of amino acids include glutamic acid, arginic acid, or sodium salts thereof. Collagen production can be promoted by including amino acids. Examples of water-soluble vitamins include ascorbyl magnesium phosphate.
- the fat-soluble vitamins include vitamin A.
- the fat-soluble vitamins By containing fat-soluble vitamins, production of mucopolysaccharides can be promoted and the skin can be moisturized.
- lipids include ceramides and phospholipids.
- Moisturizing effect is achieved by including lipids.
- mucopolysaccharides include hyaluronic acid and the like.
- a moisturizing effect is achieved by including mucopolysaccharides.
- the surfactant include polyethylene glycol and stearic acid derivatives. By including a surfactant, the dispersibility of fine particles and fat-soluble components such as vitamin A is improved.
- the blending amount of the calcium phosphate fine particles in the breast augmentation agent according to the best mode can be adjusted as appropriate, but is preferably 0.01 to 30% by mass based on the total mass of the breast augmentation agent. 1 to 15% by mass is more preferable, and 0.1 to 10% by mass is more preferable.
- the blending amount of the other breast augmentation active ingredients is not particularly limited, but is preferably 0.01 to 30% by mass, more preferably 0.1 to 15% by mass based on the total mass of the breast augmentation promoter. 0.1 to 10% by mass is more preferable.
- the blending amount of the alcohols is not particularly limited, but is preferably 0.01 to 70% by mass, more preferably 0.01 to 50% by mass based on the total mass of the breast augmentation agent, and More preferably, the content is from 01 to 30% by mass.
- the blending amount of the saccharide is not particularly limited, but is preferably 0.01 to 70% by mass, more preferably 0.01 to 50% by mass based on the total mass of the breast augmentation agent, More preferable is 30% by mass.
- the blending amount of the proteins is not particularly limited, but is preferably 0.01 to 30% by mass, more preferably 0.01 to 20% by mass based on the total mass of the breast augmentation agent, and More preferably, the content is from 01 to 10% by mass.
- the compounding amount of the amino acids is not particularly limited, but is preferably 0.01 to 30% by mass, more preferably 0.01 to 20% by mass based on the total mass of the breast augmentation promoter, and More preferably, the content is from 01 to 10% by mass.
- the blending amount of the water-soluble vitamins is not particularly limited, but is preferably 0.001 to 30% by mass, more preferably 0.001 to 20% by mass based on the total mass of the breast augmentation promoter, 0.001 to 10% by mass is more preferable.
- the blending amount of the fat-soluble vitamins is not particularly limited, but is preferably 0.001 to 30% by mass, more preferably 0.001 to 20% by mass based on the total mass of the breast augmentation promoter, 0.001 to 10% by mass is more preferable.
- the blending amount of the lipid is not particularly limited, but is preferably 0.001 to 30% by mass, more preferably 0.001 to 20% by mass based on the total mass of the breast augmentation promoter, 0.001 ⁇ 10% by weight is more preferred.
- the blending amount of the mucopolysaccharide is not particularly limited, but is preferably 0.01 to 70% by mass, more preferably 0.01 to 50% by mass based on the total mass of the breast augmentation agent, and 0 More preferred is 0.01 to 30% by mass.
- the blending amount of the surfactant is not particularly limited, but is preferably 0.001 to 30% by mass, more preferably 0.001 to 20% by mass based on the total mass of the breast augmentation promoter, and 0 0.001 to 10% by mass is more preferable.
- the calcium phosphate fine particles may be artificially produced by a known production method such as a wet method, a dry method, a hydrolysis method, or a hydrothermal method, and may be naturally derived from bone, teeth, etc. It may be. Alternatively, calcium phosphate particles having a large particle diameter may be produced and pulverized by a known method.
- Calcium phosphate fine particles are preferably obtained by sintering amorphous calcium phosphate.
- a lower limit of sintering temperature 500 degreeC or more is more preferable. If the sintering temperature is lower than 500 ° C., the sintering may not be sufficient.
- the upper limit of the sintering temperature is more preferably 1800 ° C. or less, further preferably 1250 ° C. or less, and particularly preferably 1200 ° C. or less. When the sintering temperature is higher than 1800 ° C., calcium phosphate may be decomposed. Therefore, by setting the sintering temperature within the above range, calcium phosphate that is difficult to dissolve in vivo (high crystallinity) can be produced.
- the sintering time is not particularly limited, and may be set as appropriate. In some cases, the particles may be fused together by sintering. In such a case, the sintered particles can be used after being pulverized.
- the calcium phosphate fine particles according to the best mode are produced by the method described later. That is, it is preferable that the method for producing calcium phosphate fine particles according to the best mode includes a dispersion firing (sintering) method including at least a mixing step and a sintering step.
- a dispersion firing method including at least a mixing step and a sintering step.
- the manufacturing method according to the best mode may include a primary particle generation step and a removal step. These processes are performed in the order of, for example, a primary particle generation process, a mixing process, a sintering process, and a removing process.
- the primary particle generation step is not particularly limited as long as it is a step capable of generating calcium phosphate fine particles, and may be appropriately selected depending on the raw material of the highly crystalline calcium phosphate fine particles to be manufactured. For example, if phosphoric acid is dropped into a calcium hydroxide slurry at room temperature, calcium phosphate (CaP) particles are precipitated.
- CaP calcium phosphate
- the method for generating primary particle groups that are fine (nanometer size) and uniform in particle size (narrow particle size distribution), such as the calcium phosphate fine particles according to the best mode can be used.
- calcium phosphate (phosphoric apatite) fine particles (primary particles) are obtained by solubilizing and mixing a calcium solution and a phosphoric acid solution in a surfactant / water / oil emulsion phase and reacting at a cloud point or higher of the surfactant. It can be synthesized.
- the size of the calcium phosphate fine particles can be controlled by changing the functional group of the surfactant and the ratio of the hydrophilic / hydrophobic ratio.
- the principle for producing the calcium phosphate fine particles will be briefly described as follows.
- the core of calcium phosphate grows in the micelle of surfactant
- the particles grow.
- the thermodynamic stability of the micelle is controlled by changing the reaction temperature (in the case where the surfactant is a nonionic surfactant, the clouding point of the surfactant should be set).
- raising the reaction temperature means lowering the ability to form surfactant micelles.
- the driving force for the growth of calcium phosphate particles which has been limited in the frame of micelles, is larger than the driving force for maintaining the frame of micelles. Therefore, the shape of the particles can be controlled using the mechanism.
- the functional group (hydrophilic site) of the surfactant and the hydrophilic / hydrophobic ratio in the molecule are important.
- the stability and cloud point of the micelle also differ depending on this difference.
- the cloud point of the surfactant varies depending on the type. Therefore, by appropriately changing the type of the surfactant, the functional group of the surfactant and the ratio of the hydrophilic / hydrophobic ratio can be changed, and the size of the calcium phosphate fine particles can be controlled.
- the type of surfactant used in the above method is not particularly limited, and other types of known anions, cations, amphoteric ions, nonionic surfactants disclosed in the above-mentioned JP-A-5-17111. It can be used by appropriately selecting from agents.
- these surfactants in the case of a nonionic surfactant, since it has a cloud point of the surfactant, it becomes easy to control the shape of the crystal using the above-mentioned mechanism.
- polyoxyethylene alkyl ether polyoxyethylene allyl ether, polyoxyethylene alkyl allyl ether, polyoxyethylene derivative, oxyethylene / oxypropylene block copolymer, sorbitan fatty acid ester, polyoxyethylene alkyl ether, polyoxyethylene allyl ether, polyoxyethylene alkyl allyl ether Oxyethylene sorbitan fatty acid ester, polyoxyethylene sorbitol fatty acid ester, glycerin fatty acid ester, polyoxyethylene fatty acid ester, polyoxyethylene alkylamine and the like can be used.
- quaternary ammonium salts such as stearylamine hydrochloride, lauryltrimethylammonium chloride, and alkylbenzenedimethylammonium chloride can be used.
- anionic surfactant sodium lauryl alcohol sulfate is used. Higher alcohol sulfates such as sodium oleyl alcohol sulfate, alkyl sulfates such as sodium lauryl sulfate and ammonium lauryl sulfate, and alkylaryl sulfonates such as sodium dodecylbenzenesulfonate and sodium dodecylnaphthalenesulfonate are available.
- amphoteric surfactant an alkyl betaine type, an alkylamide betaine type, an amine oxide type, or the like can be used.
- Said surfactant is used by 1 type or in combination of 2 or more types.
- pentaethylene glycol dodecyl ether particularly from the viewpoint of cloud point and solubility.
- oil phase usable in the above method examples include hydrocarbons such as toluene, xylene, hexane, dodecane, and cyclohexane, halogenated hydrocarbons such as chlorobenzene and chloroform, ethers such as diethyl ether, and alcohols such as butanol. , Ketones such as methyl isobutyl ketone, cyclohexanone, etc., and these solvents have low water solubility depending on the surfactant used, and one or two of the above-mentioned surfactants are dissolved so as to dissolve any of the above surfactants. Select a species.
- hydrocarbons such as toluene, xylene, hexane, dodecane, and cyclohexane
- halogenated hydrocarbons such as chlorobenzene and chloroform
- ethers such as diethyl ether
- alcohols such as butanol.
- the reaction temperature, reaction time, addition amount of the raw material, and the like may be adopted after selecting optimal conditions according to the composition of the primary particles.
- the upper limit of the reaction temperature is an aqueous solution reaction, it is preferably a temperature at which the solution does not boil, and preferably 90 ° C. or less.
- this step may include a step of washing the generated primary particles with water or the like, and a step of collecting the primary particles by centrifugation, filtration, or the like.
- the mixing step is a step of mixing the primary particles and the anti-fusing agent. By interposing an anti-fusing agent between the particles of the primary particle group obtained by the primary particle generation step, it is possible to prevent the fusion of primary particles in the subsequent sintering step. It is.
- the mixture of primary particles and anti-fusing agent obtained by the mixing step is called “mixed particles”.
- the “fusion preventive agent” is not particularly limited as long as it can prevent fusion between primary particles, but may be non-volatile at a sintering temperature in a subsequent sintering step. preferable. Because it is non-volatile under the sintering temperature condition, it does not disappear from the primary particles during the sintering process, and the fusion of the primary particles can be reliably prevented. However, it is not necessary to have 100% non-volatility at the sintering temperature, as long as it is non-volatile so that 10% or more remains between the primary particles after the sintering process is completed.
- the anti-fusing agent may be chemically decomposed by heat after completion of the sintering process. That is, if it remains after the end of the sintering process, it is not necessary to be the same substance (compound) before and after the start of the sintering process.
- the anti-fusing agent is preferably a substance that is soluble in a solvent, particularly an aqueous solvent.
- a solvent particularly an aqueous solvent.
- an anti-fusing agent that dissolves in a solvent as an anti-fusing agent, it is possible to prevent adhesion by simply suspending calcium phosphate fine particles mixed with the anti-fusing agent in an aqueous solvent such as pure water. Agents (such as calcium carbonate) can be removed.
- the anti-fusing agent is soluble in an aqueous solvent, it is not necessary to use an organic solvent to remove the anti-fusing agent. It becomes. Therefore, it can be said that the anti-fusing agent can be removed from the calcium phosphate fine particles more easily.
- it does not specifically limit as said solvent For example, water, ethanol, methanol etc. are mentioned as an aqueous solvent, Acetone, toluene etc. are mentioned as an organic solvent.
- the aqueous solvent may contain a chelate compound such as oxalate, ethylenediamine, bipyridine, and ethylenediaminetetraacetate in order to increase the solubility of the anti-fusing agent in water. Further, the aqueous solvent may contain electrolyte ions such as sodium chloride, ammonium nitrate and potassium carbonate in order to increase the solubility of the anti-fusing agent in water.
- a chelate compound such as oxalate, ethylenediamine, bipyridine, and ethylenediaminetetraacetate in order to increase the solubility of the anti-fusing agent in water.
- electrolyte ions such as sodium chloride, ammonium nitrate and potassium carbonate in order to increase the solubility of the anti-fusing agent in water.
- the preferable solubility is preferably 0.01 g or more, more preferably 1 g or more, and most preferably 10 g or more, when the amount of solute (g) with respect to 100 g of solvent is the solubility.
- the anti-fusing agent examples include calcium chloride, calcium oxide, calcium sulfate, calcium nitrate, calcium carbonate, calcium hydroxide, calcium acetate, calcium citrate, and other calcium salts (or complexes), potassium chloride, and potassium oxide.
- Potassium salts such as potassium sulfate, potassium nitrate, potassium carbonate, potassium hydroxide, potassium phosphate, sodium salts such as sodium chloride, sodium oxide, sodium sulfate, sodium nitrate, sodium carbonate, sodium hydroxide, sodium phosphate, etc. It is done.
- the method of mixing the primary particles and the anti-fusing agent in the mixing step is not particularly limited, and after mixing the solid anti-fusing agent with the solid primary particles, the mixture is mixed using a blender. Or a method of dispersing primary particles in a solution of an anti-fusing agent.
- the latter is a preferable method for interposing the anti-fusing agent uniformly and reliably between the primary particles.
- the hydroxyapatite (HAp) primary particle 0.5g is disperse
- the mixing step includes a solution containing a polymer compound having any of a carboxyl group, a sulfuric acid group, a sulfonic acid group, a phosphoric acid group, a phosphonic acid group, an amino group, or a salt thereof in the side chain, and the primary particles described above. May be added, and a metal salt (alkali metal salt and / or alkaline earth metal salt and / or transition metal salt) may be further added.
- the polymer compound is adsorbed on the surface of calcium phosphate ⁇ hydroxyapatite (HAp) ⁇ to reliably prevent calcium phosphate ⁇ hydroxyapatite (HAp) ⁇ from contacting each other in the anti-fusing agent mixing process.
- a polymer compound having a carboxyl group, a sulfate group, a sulfonic acid group, a phosphoric acid group, a phosphonic acid group, an amino group or a salt thereof in the side chain is simply referred to as “polymer”. Referred to as "compound”.
- the polymer compound is not particularly limited as long as it is a compound having any of a carboxyl group, a sulfate group, a sulfonic acid group, a phosphoric acid group, a phosphonic acid group, an amino group or a salt thereof in the side chain.
- Examples of the polymer compound having a carboxyl group in the side chain include polyacrylic acid, polymethacrylic acid, sodium polyacrylate, sodium polymethacrylate, carboxymethylcellulose, styrene-maleic anhydride copolymer, and the like.
- polymer compound having a sulfate group in the chain examples include polyacrylic acid alkyl sulfate ester, polymethacrylic acid alkyl sulfate ester, polystyrene sulfate, etc.
- polymer compound having a sulfonic acid group in the side chain includes polyacrylic acid.
- examples thereof include alkyl sulfonic acid esters, polymethacrylic acid alkyl sulfonic acid esters, polystyrene sulfonic acid, etc.
- polymer compounds having a phosphate group in the side chain include polyacrylic acid alkyl phosphoric acid esters and polymethacrylic acid alkyl phosphoric acid esters.
- Examples of the polymer compound having a phosphonic acid group in the side chain include polyacrylic acid alkylphosphonic acid ester, polymethacrylic acid alkylphosphonic acid ester, polystyrene phosphonic acid, polyacryloylamino. Examples thereof include methylphosphonic acid and polyvinylalkylphosphonic acid. Examples of the polymer compound having an amino group in the side chain include polyacrylamide, polyvinylamine, polymethacrylic acid aminoalkyl ester, polyaminostyrene, polypeptide, protein and the like. In the mixing step, any one of the above polymer compounds may be used, but a plurality of types of polymer compounds may be mixed and used.
- the molecular weight of the polymer compound is not particularly limited, but is preferably 100 g / mol or more and 1,000,000 g / mol or less, more preferably 500 g / mol or more and 500,000 g / mol or less, and 1,000 g / Mol to 300,000 g / mol is most preferred. If the ratio is less than the above preferable range, the ratio of entering between the primary particles decreases, and the ratio of preventing contact between the primary particles decreases. On the other hand, when the above preferred range is exceeded, the solubility of the polymer compound becomes low, and the operability such as increase in the viscosity of the solution containing the polymer compound becomes unfavorable.
- the solution containing the polymer compound is preferably an aqueous solution. This is because the calcium phosphate ⁇ hydroxyapatite (HAp) ⁇ sintered body particles are dissolved under strong acidic conditions.
- the pH of the aqueous solution containing the polymer compound is not particularly limited as long as the pH is 5 or more and 14 or less and the HAp particles are insoluble.
- the aqueous solution containing the polymer compound may be prepared by dissolving the polymer compound in distilled water, ion-exchanged water or the like, and adjusting the pH with an aqueous solution of ammonia aqueous solution, sodium hydroxide, potassium hydroxide or the like.
- the concentration of the polymer compound contained in the aqueous solution is preferably 0.001% w / v or more and 50% w / v or less, more preferably 0.005% w / v or more and 30% w / v or less. Most preferred is 01% w / v or more and 10% w / v or less.
- the amount is less than the above preferable range, the amount of entering between the primary particles is small, and the ratio of preventing contact between the primary particles is low.
- the above preferred range is exceeded, it is not preferable because dissolution of the polymer compound becomes difficult and operability such as increase in the viscosity of the solution containing the polymer compound becomes worse.
- the solution containing the polymer compound and primary particles are mixed.
- Such mixing may be performed by, for example, adding primary particles into the solution and dispersing the primary particles by a stirring operation or the like.
- the polymer compound is adsorbed on the surface of the primary particles, and the carboxyl group, sulfate group, sulfonate group, phosphate group, phosphonate group, amino group, or these Can be added to the surface of the primary particles.
- the carboxyl group, sulfuric acid group, sulfonic acid group, phosphoric acid group, phosphonic acid group or amino group is present in an ionic state in the solution.
- a metal salt an alkali metal salt and / or an alkaline earth metal salt and / or a transition metal salt
- a metal salt an alkali metal salt and / or an alkaline earth metal salt and / or a transition metal salt
- carboxylate, sulfate, sulfonate, phosphate, phosphonate, and amino acid salt are formed on the surface of the primary particles.
- Carboxylic acid salts, sulfates, sulfonates, phosphates, phosphonates, and amino acid salts of such metals function as the anti-fusing agent. . Therefore, primary particles with metal (alkali metal and / or alkaline earth metal and / or transition metal) carboxylate, sulfate, sulfonate, phosphate, phosphonate, amino acid salt formed on the surface are These are so-called “mixed particles”.
- the precipitate After being recovered, it may be dried and subjected to a sintering step described later.
- the drying is, for example, under reduced pressure (1 ⁇ 10 5 Pa or more and 1 ⁇ 10 ⁇ 5 Pa or less, preferably 1 ⁇ 10 3 Pa or more and 1 ⁇ 10 ⁇ 3 Pa or less, more preferably 1 ⁇ 10 2 Pa or more and 1 ⁇ 10 ⁇ 2 Pa or less is most preferable) and heating (preferably 0 ° C. or more and 200 ° C.
- the drying is preferably performed under reduced pressure because the drying temperature can be lowered, but may be performed under atmospheric pressure.
- the alkali metal salt is not particularly limited.
- alkaline earth metal salt examples include magnesium chloride, magnesium hypochlorite, magnesium chlorite, magnesium bromide, magnesium iodide, magnesium iodide, magnesium oxide, magnesium peroxide, magnesium sulfate, and magnesium thiosulfate.
- transition metal salt examples include zinc chloride, zinc hypochlorite, zinc chlorite, zinc bromide, zinc iodide, zinc iodide, zinc oxide, zinc peroxide, zinc sulfate, zinc thiosulfate, and selenium.
- metal salt alkali metal salt, alkaline earth metal salt, transition metal salt
- the metal salt alkali metal salt, alkaline earth metal salt, transition metal
- the metal salt may be in a solid state, but can be added uniformly and the concentration can be controlled. It is preferable to add as an aqueous solution.
- the amount (concentration) of the metal salt (alkali metal salt and / or alkaline earth metal salt and / or transition metal salt) to be added depends on the carboxylate ion, sulfate ion, sulfonate ion, phosphoric acid present on the primary particle surface. Bonded with ions, phosphonate ions, amino ions, carboxylate, sulfate, sulfonate, phosphate, phosphonate of metal (alkali metal and / or alkaline earth metal and / or transition metal), The conditions are not particularly limited as long as the amino acid salt is generated, and may be determined after appropriate examination.
- the salt undergoes thermal decomposition in a sintering process described later, and becomes an oxide of a metal (an alkali metal and / or an alkaline earth metal and / or a transition metal).
- a metal an alkali metal and / or an alkaline earth metal and / or a transition metal
- the metal oxide alkali metal oxide and / or alkaline earth metal oxide (for example, calcium oxide) and / or transition metal oxide) is water-soluble, it can be easily removed by a removal step described later. Is possible.
- sodium polyacrylate Since sodium polyacrylate is soluble in water, it can be used as an anti-fusing agent in this mixing step. However, since calcium polyacrylate is insoluble in water, only polyacrylic acid is temporarily removed from the primary particle surface. It is preferable that calcium acrylate is precipitated on the primary particle surface by adding a calcium salt or the like after adsorbing to the primary particle surface.
- the polymer compound decomposes when the primary particles are calcined at a high temperature (about 300 ° C. or higher), the metal salt of the polymer compound is added to the primary particles so that it functions as an anti-fusing agent even after calcining. It can be said that it is preferable to deposit on the surface. However, when the primary particles are calcined (heat treatment) at a temperature at which the polymer compound is not decomposed (not softened), it is not particularly necessary to deposit the metal salt of the polymer compound on the surface of the primary particles.
- the sintering step is a step in which the mixed particles obtained in the mixing step are exposed to a sintering temperature to make primary particles contained in the mixed particles into highly crystalline calcium phosphate fine particles (sintered particles). Since the anti-fusing agent is interposed between the primary particles, it is possible to prevent the primary particles from fusing even when exposed to high temperature conditions in the sintering process.
- the sintering temperature in the sintering step may be appropriately set so that the hardness of the highly crystalline calcium phosphate fine particles becomes a desired hardness. For example, it is more preferably in the range of 100 ° C. to 1800 ° C., and 150 ° C. to 1500 ° C. Is more preferable, and 200 ° C. to 1200 ° C. is most preferable.
- the sintering time may be appropriately set based on the desired hardness of the highly crystalline calcium phosphate fine particles. In the examples described later, sintering is performed at 800 ° C. for 1 hour.
- the apparatus etc. which are used for the said sintering process are not specifically limited, What is necessary is just to employ
- the said removal process is a process of removing the anti-fusing agent mixed between the particles of the highly crystalline calcium phosphate fine particles obtained by the sintering process.
- the removal means and method may be appropriately employed according to the anti-fusing agent employed in the mixing step.
- anti-fusing agent having solvent solubility
- anti-fusing can be prevented by using a solvent that does not dissolve the calcium phosphate fine particles (non-soluble) and a solvent that dissolves the anti-fusing agent (soluble). Only the agent can be dissolved and removed.
- the solvent to be used is not particularly limited as long as it satisfies the above requirements, and may be an aqueous solvent or an organic solvent.
- water, ethanol, methanol, etc. are mentioned as an aqueous solvent
- acetone, toluene, etc. are mentioned as an organic solvent.
- the aqueous solvent may contain a chelate compound such as oxalate, ethylenediamine, bipyridine, and ethylenediaminetetraacetate in order to increase the solubility of the anti-fusing agent in water. Further, the aqueous solvent may contain electrolyte ions such as sodium chloride, ammonium nitrate and potassium carbonate in order to increase the solubility of the anti-fusing agent in water.
- a chelate compound such as oxalate, ethylenediamine, bipyridine, and ethylenediaminetetraacetate in order to increase the solubility of the anti-fusing agent in water.
- electrolyte ions such as sodium chloride, ammonium nitrate and potassium carbonate in order to increase the solubility of the anti-fusing agent in water.
- the solvent used is preferably an aqueous solvent.
- the removal step is preferably performed at 0 to pH 12.0.
- the above operation is not limited to once, and may be performed twice or more. It can be said that the removal rate of the calcium phosphate anti-fusing agent is further improved by performing the above operation a plurality of times. However, it is not preferable to perform the above operation more than necessary because the manufacturing process becomes complicated, the manufacturing cost increases, and the recovery rate of calcium phosphate decreases. Therefore, the number of operations may be appropriately determined based on the target anti-fusing agent removal rate.
- this step may include a step of classifying in order to make the particle diameter uniform.
- the anti-fusing agent can be removed using a magnet by using a magnetic substance as the anti-fusing agent. More specifically, after the calcium phosphate particles (crude calcium phosphate particles) containing the anti-fusing agent obtained by the sintering step are suspended and dispersed in an appropriate solvent (water or the like), the magnetic force is applied to the suspension. , Only the anti-fusing agent is adsorbed to the magnet, and only the calcium phosphate particles that have not been adsorbed are recovered. In addition, without suspending in a solvent, a method may be used in which the crude calcium phosphate particles are ground into powder and then the anti-melting agent is separated by a magnet.
- the calcium phosphate particles to which this method can be applied are preferably non-magnetic or weakly magnetic.
- the calcium phosphate particles according to the best mode are primary particles whose majority is a single crystal, or a particle lump (single crystal primary particles) in which the primary particles composed of the single crystals are assembled by ionic interaction, And dispersibility is good, and since the secondary particles are not formed, the surface area is also high.
- the result of measuring the particle size by observation with an electron microscope and the particle size in a state suspended in a solvent by a dynamic light scattering method By comparing the results with the measurement results, it can be determined that most of the calcium phosphate particles according to the present best form are in the state of primary particles if the results are almost the same. If the particle diameter measurement result by the dynamic light scattering method is larger than the particle diameter measurement result obtained by the above, it can be determined that the primary particles are fused to form secondary particles.
- the solvent for dispersing the calcium phosphate particles according to the best mode is not particularly limited as long as it does not dissolve the calcium phosphate particles.
- water alcohols such as methanol and ethanol, ketones such as acetone, methyl ethyl ketone, methyl isobutyl ketone, cyclohexanone, amides such as N, N-dimethylformamide, sulfoxides such as dimethyl sulfoxide, toluene, xylene, hexane , Hydrocarbons such as dodecane and cyclohexane, halogenated hydrocarbons such as chlorobenzene and chloroform, ethers such as diethyl ether and dioxane, etc., and these solvents are selected according to the purpose of use. Can be used.
- At least 50% or more is a single crystal primary. It exists as particles, and in a more preferable case, 60% or more exists as single crystal primary particles, and under the most preferable conditions, 70% or more can exist as single crystal primary particles.
- the breast augmentation promoting method for applying the breast augmentation agent according to the best mode to the chest is not particularly limited. For example, 1 to 3 times a day (preferably 2 times), 250 to 4000 mg (preferably 500 to 2000 mg, more preferably 1000 mg) at a time (however, 10 to 300 mg of calcium phosphate (preferably 25 to 200 mg, more preferably 50 mg)), and it is effective when used as an outer skin applied to the chest (particularly the upper chest). In addition, when used continuously over a long period of time, such as one week to one year, further efficacy is demonstrated.
- Production Example 1 (Production of calcium phosphate fine particles) (Primary particle generation process) Dodecane [CH 3 (CH 2 ) 10 CH 3 ] as a continuous oil phase and pentaethylene glycol dodecyl ether [CH 3 (CH 2 ) 10 CH 2 O (CH 2 CH 2 ) having a cloud point of 31 ° C. as a nonionic surfactant O) 4 CH 2 CH 2 OH]. At room temperature, 40 ml of a continuous oil phase containing 0.5 g of the nonionic surfactant was prepared.
- a 2.5 mol / l calcium hydroxide [Ca (OH) 2 ] dispersed aqueous solution was added to the continuous oil phase prepared above to prepare a water-in-oil solution (W / O solution). While stirring the W / O solution, 10 ml of a 1.5 mol / l potassium dihydrogen phosphate [(KH 2 PO 4 )] solution was added thereto. And it was made to react, stirring for 24 hours at room temperature. Next, hydroxyapatite (HAp) primary particle groups were obtained by separating and washing the obtained reaction product by centrifugation.
- HAp hydroxyapatite
- Production Example 2 (Unfired) Except that the reaction temperature in the primary particle generation step is 30 ° C., only the primary particle generation step is performed under the same conditions as in Production Example 1, and the subsequent steps such as the subsequent mixing step and the sintering step are not performed. Two unfired hydroxyapatite fine particles were obtained. Hereinafter, detailed information on the hydroxyapatite fine particles will be described.
- a breast augmentation promoter having the following composition was used. Hydroxyapatite (fired) of Production Example 1: 5% by mass Glycerin: 6% by mass Polyethylene glycol: 14% by mass Water: 75% by mass
- the breast augmentation promoter of the above formulation was applied to the chest twice a day in the morning and evening, 1000 mg, continuously for a total of 9 days. After the application on the morning of the fourth day, it was felt that the elasticity of the breast epidermis and the elasticity of the breast were improved compared to before application.
- FIG. 1 is a graph showing the relationship between the number of times of application and the actual feeling index of the subject in the breast augmentation promotion test.
- skin of skin and “elasticity felt by pushing with a finger” were adopted.
- the “skin of the epidermis” means the skin firmness that the subject feels sensuously, and is intended to evaluate the manifestation of the effect of promoting breast augmentation in the epidermis.
- Elasticity felt by pressing with a finger means the elasticity felt by the subject pressing the application site with a finger, and is intended to evaluate the effect on the entire skin including not only the epidermis but also the dermis.
- the “realistic index” employed in the vertical axis of the graph is a test when the maximum value of “skin elasticity” or “elasticity felt by pushing with a finger” that can be experienced in real life is assumed to be 100 in the test subject's experience.
- “the elasticity of the epidermis” or “elasticity felt by pressing with a finger” is a value obtained by comparing and evaluating the above maximum value.
- ⁇ Breast augmentation test 2 (effect of long-term administration)>
- the breast augmentation agent used in breast augmentation promotion test 1 was continuously administered to two subjects A and B twice a day for two months each morning and evening (applicable amount: per one) About 500 mg, that is, about 1 g per time), the following questions were filled in with the impression after application. Impressions of the questions were evaluated as a total of 9 grades: 0 for “no change”, 4 grades from +1 to +4 for the rise, and 4 grades for -1 to -4 for the fall. Details and details of the evaluation are shown in Table 2 and Table 3, respectively.
Abstract
Description
リン酸カルシウムを含有する一次粒子と融着防止剤とを混合する、混合工程と、
上記混合工程によって得られた混合粒子を焼結温度に曝す、焼結工程と、
を含む方法により製造された、前記発明(4)の豊胸促進剤である。
次に、本最良形態に係るリン酸カルシウム微粒子の製造方法について説明する。リン酸カルシウム微粒子は、湿式法や、乾式法、加水分解法、水熱法等の公知の製造方法によって、人工的に製造されたものであってもよく、また、骨、歯等から得られる天然由来のものであってもよい。また、粒径の大きなリン酸カルシウム粒子を製造して、周知の方法により粉砕したものであってもよい。
当該一次粒子生成工程は、リン酸カルシウム微粒子を生成することができる工程であれば特に限定されるものではなく、製造する高結晶性リン酸カルシウム微粒子の原料により適宜選択の上、採用すればよい。例えば、常温下において水酸化カルシウムスラリーにリン酸を滴下すれば、リン酸カルシウム(CaP)の粒子が沈殿する。
当該混合工程は、一次粒子と融着防止剤とを混合する工程である。上記一次粒子生成工程によって得られた一次粒子群の粒子間に、あらかじめ融着防止剤を介在させておくことで、その後の焼結工程における一次粒子同士の融着を防止することができるというものである。尚、当該混合工程によって得られた一次粒子と融着防止剤との混合物を「混合粒子」と呼ぶ。
当該焼結工程は、上記混合工程によって得られた混合粒子を焼結温度に曝して、当該混合粒子に含まれる一次粒子を高結晶性リン酸カルシウム微粒子(焼結体粒子)にする工程である。一次粒子の粒子間に融着防止剤が介在しているために、焼結工程における高温条件に曝された場合であっても一次粒子同士の融着を防止することができるというものである。
当該除去工程は、焼結工程によって得られた高結晶性リン酸カルシウム微粒子の粒子間に混在する融着防止剤を取り除く工程である。
上記、本最良形態に係るリン酸カルシウム粒子の製造方法によって製造されたリン酸カルシウム粒子は、融着防止剤の作用によって一次粒子同士の融着が防止されているために、その過半数が一次粒子の状態をキープしている。よって、当該高結晶性リン酸カルシウム粒子を溶媒中に懸濁した際には、高結晶性リン酸カルシウム粒子の過半数が単結晶からなる一次粒子又は前記単結晶からなる一次粒子がイオン的相互作用にて集合化した粒子塊(単結晶一次粒子)で分散することができる。
本最良形態に係る豊胸促進剤を胸部に塗布する豊胸促進方法は、特に限定されない。例えば、一日1~3回(好適には2回)、一回250~4000mg(好適には、500~2000mg、更に好適には1000mg)(但し、この中にリン酸カルシウムが10~300mg(好適には25~200mg、より好適には50mg)含まれる)、胸部(特に上方胸部)に塗布する外皮用として用いることにより効能を発揮する。さらに、1週間~1年といった長期間継続的に用いることにより、さらなる効能を発揮する。
(一次粒子生成工程)
連続オイル相としてドデカン〔CH3(CH2)10CH3〕、非イオン性界面活性剤として曇点31℃のペンタエチレングリコールドデシルエーテル〔CH3(CH2)10CH2O(CH2CH2O)4CH2CH2OH〕を用いた。室温において、上記非イオン性界面活性剤0.5gを含有している連続オイル相40mlを調製した。次に、上記で調製した連続オイル相に2.5mol/l水酸化カルシウム〔Ca(OH)2〕分散水溶液10mlを添加し、油中水滴型溶液(W/O溶液)を調製した。上記W/O溶液を攪拌しながら、そこに1.5mol/lリン酸二水素カリウム〔(KH2PO4)〕溶液を10ml添加した。そして、24時間、室温で撹拌しながら反応させた。次に、得られた反応物を遠心分離により分離洗浄することにより、ハイドロキシアパタイト(HAp)一次粒子群を取得した。
1.0gのポリアクリル酸ナトリウム(ALDRICH社製、重量平均分子量15,000g/mol)を含むpH12.0の水溶液100mlに、1.0gのハイドロキシアパタイト(HAp)一次粒子群を分散させることで、同粒子表面にポリアクリル酸ナトリウムを吸着させた。この水溶液のpHは株式会社 堀場製作所製pHメータD-24SEを用いて測定した。
上記混合粒子をルツボに入れ、焼結温度800℃にて1時間焼結を行なった。この際、ポリアクリル酸カルシウムは熱分解し、酸化カルシウム〔CaO〕となった。焼結工程終了後の酸化カルシウム〔CaO〕の残存率は25%以上であった。
融着防止剤の水への溶解性を上げるために、50mmol/l硝酸アンモニウム〔NH4NO3〕水溶液を調製した。次に、上記で調製した水溶液500mlに、上記工程にて得られた焼結体を懸濁し、遠心分離により分離洗浄し、さらに蒸留水に懸濁し、同様に遠心分離により分離洗浄を行なうことによって、融着防止剤及び硝酸アンモニウムを除去し、高結晶性ハイドロキシアパタイト(HAp)微粒子を回収した。これらの工程により得られたハイドロキシアパタイト微粒子の詳細な情報については、以下にまとめた。
形状:球状
平均粒径(電子顕微鏡より):28nm
変動係数:14%
一次粒子生成工程における反応温度を30℃としたこと以外では製造例1と同条件で一次粒子生成工程をのみ行い、その後の混合工程や焼結工程等のその後の工程を行わないで、製造例2の未焼成のハイドロキシアパタイト微粒子を得た。以下、当該ハイドロキシアパタイト微粒子の詳細な情報について記載する。
形状:粒子形状
平均粒径(電子顕微鏡より):42nm
変動係数:17%
正常ヒト線維芽細胞を試料含有0.5%FBS-DMEM培地にて24時間培養後、培地中のコラーゲン量をELISAにて定量した。当該実験はそれぞれの条件において6回反復して行なった(n=6)。陽性コントロール(P.C.)には、アルコルビン酸リン酸マグネシウム(VCPMg)を用いた。尚、用いた試料は、製造例1において製造した焼成のハイドロキシアパタイトと、製造例2において使用した未焼成したハイドロキシアパタイトである。結果を表1に示した。ここで、表1中の「mean」は、測定で得られたコラーゲン量の実測値(平均値)を示しており、「SD」とは、標準偏差を示しており、「p(t-test)」とは、「t-test」により得られたp値{一般的に0.05(厳密に議論する場合は、0.01)以下であれば、差がある値であることを示し、逆に、0.05より大きな値である場合、差がほとんどないことを示す。}を示している。
試験条件:被験者成人女性に試験内容、趣旨を説明したのち、前腕部にてパッチテストを行い異常が認められないことを確認した上で、本発明に係る豊胸促進剤の効果を調査した。
製造例1のハイドロキシアパタイト(焼成):5質量%
グリセリン:6質量%
ポリエチレングリコール:14質量%
水:75質量%
長期投与における効果を調査する目的で、2名の被験者A及びBに豊胸促進試験1で用いた豊胸促進剤を2ヶ月間朝晩の一日二回ずつ継続投与し(適用量:片方あたり約500mg、即ち、1回あたり約1g)、以下に示す設問に塗布後の感想を記入してもらった。設問に対する感想を、「変わらない」を0、上がった程度を+1~+4の4段階、下がった程度を-1~-4の4段階と、計9段階との評価とした。評価の詳細及び詳細を表2及び表3にそれぞれ示す。
2ヶ月継続した試験により、いずれの設問においても継続性、即効性共に使用前に比べ改善した意見のみであった。ハリについては、即効性、持続性共に同等のスコアであり、初期に獲得したハリが維持されることを示唆している。ボリュームについては、即効性に比べ継続性に関するスコアが高いことから試用期間の経過と共にボリュームアップの効果が獲得できていることを示唆している。いずれの被験者も弾力の改善(即効性、継続性ともに)に関する効果を認めている。
豊胸促進試験2を経た被験者A及びBについて、塗布前後におけるバスト状態の変化を検証するために、エコー断面写真の撮影を行った。図2及び図3に結果を示す。写真に向かって左側が適用前の画像で、(C)「白点間の距離」が胸部皮下組織の厚みである。対して、右側が2ヶ月(材適応並びに問診期間)後の画像で、(C)「白点間の距離」が胸部皮下組織の厚みである。いずれの被験者も胸部皮下組織が厚くなり効果が認められた。
Claims (6)
- リン酸カルシウム微粒子を含有することを特徴とする豊胸促進剤。
- 前記リン酸カルシウム微粒子がハイドロキシアパタイト微粒子である、請求項1記載の豊胸促進剤。
- 前記リン酸カルシウム微粒子の平均粒子径が、10~1,000nmである、請求項1又は2記載の豊胸促進剤。
- 前記リン酸カルシウム微粒子が、焼結体である、請求項1~3のいずれか一項記載の豊胸促進剤。
- 前記焼結体が、
リン酸カルシウムを含有する一次粒子と融着防止剤とを混合する、混合工程と、
上記混合工程によって得られた混合粒子を焼結温度に曝す、焼結工程と、
を含む方法により製造された、請求項4記載の豊胸促進剤。 - 外用である、請求項1~5のいずれか一項記載の豊胸促進剤。
Priority Applications (4)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
EP11844849.7A EP2647383A4 (en) | 2010-12-01 | 2011-12-01 | ACCELERATOR OF MAMMARY INCREASE |
KR1020137016724A KR20140012959A (ko) | 2010-12-01 | 2011-12-01 | 유방 확대 촉진제 |
US13/989,865 US20130273166A1 (en) | 2010-12-01 | 2011-12-01 | Breast enhancement accelerator |
JP2012546924A JP5859458B2 (ja) | 2010-12-01 | 2011-12-01 | 豊胸促進剤 |
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP2010268837 | 2010-12-01 | ||
JP2010-268837 | 2010-12-01 |
Publications (1)
Publication Number | Publication Date |
---|---|
WO2012074037A1 true WO2012074037A1 (ja) | 2012-06-07 |
Family
ID=46171962
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/JP2011/077743 WO2012074037A1 (ja) | 2010-12-01 | 2011-12-01 | 豊胸促進剤 |
Country Status (5)
Country | Link |
---|---|
US (1) | US20130273166A1 (ja) |
EP (1) | EP2647383A4 (ja) |
JP (1) | JP5859458B2 (ja) |
KR (1) | KR20140012959A (ja) |
WO (1) | WO2012074037A1 (ja) |
Cited By (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2018043621A1 (ja) * | 2016-08-30 | 2018-03-08 | 株式会社ソフセラ | リン酸カルシウム焼結体粒子及びその製造方法 |
WO2018043622A1 (ja) * | 2016-08-30 | 2018-03-08 | 株式会社ソフセラ | 新規なセラミック粒子複合材料 |
Families Citing this family (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP3480166A4 (en) * | 2016-06-30 | 2020-03-25 | Sofsera Corporation | CALCIUM PHOSPHATE SINTERED BODY PARTICLES AND PROCESS FOR PRODUCING THE SAME |
US20200000684A1 (en) * | 2016-08-30 | 2020-01-02 | Sofsera Corporation | Ceramic particle carrying medical tube and/or cuff |
US20190290807A1 (en) * | 2016-08-30 | 2019-09-26 | Sofsera Corporation | Ceramic particle carrying stent |
Citations (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPH0517111A (ja) | 1991-02-21 | 1993-01-26 | Ricoh Co Ltd | 水酸アパタイト超微粒子 |
JP2000302667A (ja) | 1999-04-23 | 2000-10-31 | Kobe Tennenbutsu Kagaku Kk | 豊胸促進剤 |
JP2002137910A (ja) | 2000-10-31 | 2002-05-14 | Japan Science & Technology Corp | ハイドロキシアパタイトナノ粒子およびその製造方法 |
JP2008044890A (ja) | 2006-08-17 | 2008-02-28 | Yaizu Suisankagaku Industry Co Ltd | 豊胸用組成物及び豊胸用飲食品 |
WO2010106668A1 (ja) * | 2009-03-19 | 2010-09-23 | サウスコーストデンタル株式会社 | 歯面修復材 |
WO2010137122A1 (ja) * | 2009-05-26 | 2010-12-02 | 株式会社ソフセラ | コラーゲン産生促進剤 |
Family Cites Families (9)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US7094282B2 (en) * | 2000-07-13 | 2006-08-22 | Calcitec, Inc. | Calcium phosphate cement, use and preparation thereof |
JP4383630B2 (ja) * | 2000-04-26 | 2009-12-16 | 株式会社サンギ | 化粧料 |
JP2003320017A (ja) * | 2002-05-07 | 2003-11-11 | Ngk Spark Plug Co Ltd | リン酸カルシウム多孔体及びその製造方法 |
JP4353694B2 (ja) * | 2002-11-28 | 2009-10-28 | 独立行政法人産業技術総合研究所 | 亜鉛徐放性リン酸カルシウムを用いた硬化性骨補填剤及び皮膚欠損治療用剤 |
KR100898218B1 (ko) * | 2004-09-14 | 2009-05-18 | 재팬 사이언스 앤드 테크놀로지 에이젼시 | 세라믹입자군 및 그 제조방법 그리고 그 이용 |
US8178066B2 (en) * | 2005-08-15 | 2012-05-15 | Kyoto University | Method for stabilizing calcium phosphates fine particles, method for manufacturing calcium phosphates fine particles by using the method, and use thereof |
FR2898807B1 (fr) * | 2006-03-23 | 2008-12-05 | Oreal | Composition comprenant de l'hydroxyapatite et un sel de calcium pour renforcer la fonction barriere de la peau et/ou des semi-muqueuses |
KR20080099040A (ko) * | 2007-05-08 | 2008-11-12 | 이은미 | 수산화인회석을 포함하는 유-무기 복합 현탁액 및 그제조방법 |
WO2010065780A1 (en) * | 2008-12-04 | 2010-06-10 | Skeletal Kinetics, Llc | Tricalcium phosphate coarse particle compositions and methods for making the same |
-
2011
- 2011-12-01 JP JP2012546924A patent/JP5859458B2/ja active Active
- 2011-12-01 WO PCT/JP2011/077743 patent/WO2012074037A1/ja active Application Filing
- 2011-12-01 US US13/989,865 patent/US20130273166A1/en not_active Abandoned
- 2011-12-01 KR KR1020137016724A patent/KR20140012959A/ko not_active Application Discontinuation
- 2011-12-01 EP EP11844849.7A patent/EP2647383A4/en not_active Withdrawn
Patent Citations (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPH0517111A (ja) | 1991-02-21 | 1993-01-26 | Ricoh Co Ltd | 水酸アパタイト超微粒子 |
JP2000302667A (ja) | 1999-04-23 | 2000-10-31 | Kobe Tennenbutsu Kagaku Kk | 豊胸促進剤 |
JP2002137910A (ja) | 2000-10-31 | 2002-05-14 | Japan Science & Technology Corp | ハイドロキシアパタイトナノ粒子およびその製造方法 |
JP2008044890A (ja) | 2006-08-17 | 2008-02-28 | Yaizu Suisankagaku Industry Co Ltd | 豊胸用組成物及び豊胸用飲食品 |
WO2010106668A1 (ja) * | 2009-03-19 | 2010-09-23 | サウスコーストデンタル株式会社 | 歯面修復材 |
WO2010137122A1 (ja) * | 2009-05-26 | 2010-12-02 | 株式会社ソフセラ | コラーゲン産生促進剤 |
Non-Patent Citations (5)
Title |
---|
BERLIN, A. ET AL.: "Calcium hydroxylapatite for facial rejuvenation", SEMIN CUTAN MED SURG, vol. 25, no. 3, 2006, pages 132 - 7, XP005703027 * |
COLEMAN, K.M. ET AL.: "Neocollagenesis after injection of calcium hydroxylapatite composition in a canine model", DERMATOL SURG, vol. 34, no. SUP.1, 2008, pages S53 - S55, XP055069455 * |
See also references of EP2647383A4 * |
VOIGTS, R. ET AL.: "Dispersion of calcium hydroxylapatite accumulations in the skin: animal studies and clinical practices", DERMATOL SURG, vol. 36, May 2010 (2010-05-01), pages 798 - 803, XP055069465 * |
YOSHIYUKI MURAKAMI: "Choki Jizokugata Hifu Jutenzai `Redeiesse' ni yoru Bishinko Chiryo no Keiken", SKIN SURG, vol. 18, no. 3, 2009, pages 158 - 163, XP008168937 * |
Cited By (9)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2018043621A1 (ja) * | 2016-08-30 | 2018-03-08 | 株式会社ソフセラ | リン酸カルシウム焼結体粒子及びその製造方法 |
WO2018043622A1 (ja) * | 2016-08-30 | 2018-03-08 | 株式会社ソフセラ | 新規なセラミック粒子複合材料 |
CN109922838A (zh) * | 2016-08-30 | 2019-06-21 | 株式会社索夫塞拉 | 新型的陶瓷粒子复合材料 |
JPWO2018043621A1 (ja) * | 2016-08-30 | 2019-07-18 | 株式会社ソフセラ | リン酸カルシウム焼結体粒子及びその製造方法 |
JPWO2018043622A1 (ja) * | 2016-08-30 | 2019-08-08 | 株式会社ソフセラ | 新規なセラミック粒子複合材料 |
US11168031B2 (en) | 2016-08-30 | 2021-11-09 | Sofsera Corporation | Calcium phosphate sintered particles and production method therefor |
JP7125755B2 (ja) | 2016-08-30 | 2022-08-25 | 株式会社ソフセラ | 新規なセラミック粒子複合材料 |
JP7125754B2 (ja) | 2016-08-30 | 2022-08-25 | 株式会社ソフセラ | リン酸カルシウム焼結体粒子及びその製造方法 |
US11504452B2 (en) | 2016-08-30 | 2022-11-22 | Sofsera Corporation | Ceramic particle composite material |
Also Published As
Publication number | Publication date |
---|---|
JPWO2012074037A1 (ja) | 2014-05-19 |
EP2647383A4 (en) | 2016-01-27 |
US20130273166A1 (en) | 2013-10-17 |
KR20140012959A (ko) | 2014-02-04 |
JP5859458B2 (ja) | 2016-02-10 |
EP2647383A1 (en) | 2013-10-09 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
JP5411932B2 (ja) | コラーゲン産生促進剤 | |
JP5506782B2 (ja) | 歯面修復材 | |
JP5859458B2 (ja) | 豊胸促進剤 | |
EP2425843B1 (en) | Dentin mineralizing agent for use in the treatment of hyperesthesia | |
KR101143262B1 (ko) | 재석회화 촉진제 및 구강용 조성물 | |
TW201536336A (zh) | 用於牙齒去敏感之經表面反應碳酸鈣 | |
TWI614032B (zh) | 牙齒抗敏組合物 | |
JP6072968B1 (ja) | リン酸カルシウム焼結体粒子の製造方法 | |
CN115024988A (zh) | 一种抗菌性牙釉质再矿化液的制备及应用 | |
JPWO2005000251A1 (ja) | 再石灰化促進剤、口腔用組成物 | |
JP6548617B2 (ja) | コラーゲン産生促進剤 | |
WO2018043621A1 (ja) | リン酸カルシウム焼結体粒子及びその製造方法 | |
JP2012012325A (ja) | 抗炎症性化合物のナノ粒子、及びその製造方法 | |
JP6555722B2 (ja) | 歯面修復材 | |
US20170087060A1 (en) | Tooth surface repairing material | |
JP2024509356A (ja) | フッ素アパタイト結晶を生成するための方法 | |
KR20200091632A (ko) | 히드록시아파타이트의 결정화 방법 및 이러한 방법으로 제조된 히드록시아파타이트 결정을 포함하는 구취제거용 조성물 | |
IT201800005561A1 (it) | Metodo per la pulizia dei denti mediante una composizione in polvere a base di idrossiapatite. | |
Füredi-Milhofer | Fiziološka i patološka mineralizacija: neki problemi i moguća rješenja |
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: 11844849 Country of ref document: EP Kind code of ref document: A1 |
|
ENP | Entry into the national phase |
Ref document number: 2012546924 Country of ref document: JP Kind code of ref document: A |
|
NENP | Non-entry into the national phase |
Ref country code: DE |
|
REEP | Request for entry into the european phase |
Ref document number: 2011844849 Country of ref document: EP |
|
WWE | Wipo information: entry into national phase |
Ref document number: 2011844849 Country of ref document: EP |
|
ENP | Entry into the national phase |
Ref document number: 20137016724 Country of ref document: KR Kind code of ref document: A |
|
WWE | Wipo information: entry into national phase |
Ref document number: 13989865 Country of ref document: US |