WO2001030367A1 - Antagonistes du facteur d'activation des plaquettes et compositions dermatologiques destinees a un usage externe contenant lesdits antagonistes - Google Patents

Antagonistes du facteur d'activation des plaquettes et compositions dermatologiques destinees a un usage externe contenant lesdits antagonistes Download PDF

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Publication number
WO2001030367A1
WO2001030367A1 PCT/JP2000/007601 JP0007601W WO0130367A1 WO 2001030367 A1 WO2001030367 A1 WO 2001030367A1 JP 0007601 W JP0007601 W JP 0007601W WO 0130367 A1 WO0130367 A1 WO 0130367A1
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Prior art keywords
skin
phase
compound
extract
external preparation
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PCT/JP2000/007601
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English (en)
Japanese (ja)
Inventor
Kazuhisa Maeda
Masahiro Ota
Koji Kobayashi
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Shiseido Company, Ltd.
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Priority claimed from JP2000309061A external-priority patent/JP2001192339A/ja
Application filed by Shiseido Company, Ltd. filed Critical Shiseido Company, Ltd.
Publication of WO2001030367A1 publication Critical patent/WO2001030367A1/fr

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    • 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
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/075—Ethers or acetals
    • A61K31/085—Ethers or acetals having an ether linkage to aromatic ring nuclear carbon
    • 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
    • A61K31/075—Ethers or acetals
    • A61K31/085—Ethers or acetals having an ether linkage to aromatic ring nuclear carbon
    • A61K31/09—Ethers or acetals having an ether linkage to aromatic ring nuclear carbon having two or more such linkages
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/88—Liliopsida (monocotyledons)
    • A61K36/906—Zingiberaceae (Ginger family)
    • A61K36/9068—Zingiber, e.g. garden ginger
    • 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
    • A61K8/96—Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution
    • A61K8/97—Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution from algae, fungi, lichens or plants; from derivatives thereof
    • A61K8/9783—Angiosperms [Magnoliophyta]
    • A61K8/9794—Liliopsida [monocotyledons]
    • 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
    • A61P7/00—Drugs for disorders of the blood or the extracellular fluid
    • A61P7/02—Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
    • 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
    • A61K2800/70—Biological properties of the composition as a whole

Definitions

  • the present invention relates to an antagonist of blood, a platelet activating factor (PAF), and various skins such as atopic dermatitis, contact dermatitis, eczema, and psoriasis.
  • PAF platelet activating factor
  • the present invention relates to a skin external preparation composition for improving and preventing a rough skin symptom due to a disease and rough and rough skin of a healthy person.
  • a skin external preparation that has the effect of improving and preventing skin roughness due to skin diseases such as atopic dermatitis, contact dermatitis, eczema, and psoriasis, as well as skin roughness and roughness of healthy people.
  • skin diseases such as atopic dermatitis, contact dermatitis, eczema, and psoriasis
  • steroid agents having anti-inflammatory effects, vaseline, urea, heparin, various amino acids, and lipids having moisturizing effect have been used.
  • steroids have a strong side effect, and moisturizers do not always have sufficient effects, and it has been desired to develop an active ingredient with higher safety.
  • PAF platelet activator
  • PAF is also considered to play an important role in the normal keratinization process of the epidermis such as keratinization. Attempts have been made to use PAF antagonists as therapeutic agents for diseases. Disclosure of the invention
  • an object of the present invention is to excel in platelet activating factor (PAF) antagonism and to improve inflammatory ⁇ allergic diseases based on PAF antagonism.
  • a platelet activating factor antagonist that has an excellent effect of improving skin roughness, and has an excellent effect of preventing various skin diseases, skin roughness, roughness, etc.Prevention and improvement of skin roughness containing it as an active ingredient
  • An object of the present invention is to provide a skin external preparation composition.
  • a platelet activating factor containing, as an active ingredient, an extract of a plant belonging to the genus Zingiberaceae (Zingibera) belonging to the genus Zingiber (Bengre, Indonesia: Benglé). , PAF) antagonist, and a skin external preparation composition for preventing and improving rough skin, comprising the active ingredient and a base acceptable as a skin external preparation.
  • a platelet activating factor antagonist comprising the following compound 1 and / or compound 2 as an active ingredient and a rough skin prevention / improvement comprising the same together with a base acceptable as an external preparation for skin A skin external preparation composition is provided.
  • FIG. 1 is a chromatogram of compound 3 according to the present invention.
  • FIG. 2 is a 13 C-NMR of compound 3 according to the present invention.
  • FIG. 3 is a 1 H-NMR of compound 3 according to the present invention. BEST MODE FOR CARRYING OUT THE INVENTION
  • bendal extract has PAF antagonism, and its application to inflammatory and allergic skin diseases and to prevent skin roughness based on PAF antagonism is also completely known. Absent.
  • other plants belonging to the genus Zingiber (Zingiberaceae) belonging to the genus Zingiberaceae have PAF antagonism.
  • the present inventors consider that PAF antagonists are effective in improving various inflammatory and allergic skin diseases and the roughening and roughening of healthy people, and thus have a wide variety of PAF antagonists.
  • the extract of Bendal Indonesia name: Bengle
  • Zingiberaceae Zingiberaceae
  • the plant extract can improve rough skin accompanied by erythema, desquamation, dryness, eczema, itching and the like.
  • the bender (Bundale, Indonesian name: Bengle) used in the present invention is a plant that is found in tropical and subtropical regions such as Southeast Asia, particularly Indonesia. According to a detailed survey of scientific names, Bendal has the scientific name, Zingiber purpur eum Roxb. One ray is called Zingiber cassumunar, and Zingiber purpur eum Roxb. And Zingiber cassumunar are It turned out to be a synonym relationship. In the present specification, what is described as the genus Zingiber is also referred to as the genus Zingiber.
  • the blending amount of the bendal extract in the present invention is 0.005 to 20.0% by weight, preferably 0.01 to 10.0% by weight as a dry solid in the total amount of the external preparation composition. If the amount is less than 0.005% by weight, the effect of the present invention is not sufficiently exhibited. Even if the amount exceeds 20.0% by weight, a further increase in the effect cannot be substantially expected. Also tend to be difficult.
  • a ginger plant extract of the genus Zingiberaceae which contains the compound 1 and Z or the compound 2 as an active ingredient.
  • the platelet activating factor antagonist is obtained by fractionating a methanol extract of a plant belonging to the genus Zingiberaceae with silica gel ram (eluent: a mixed solvent of n-hexane and ethyl acetate), The resulting fraction is further fractionated on a reversed-phase open column (eluent: mixed solvent of methanol and Z water), and the resulting fraction is subjected to reversed-phase HPLC (mobile phase: 50% acetate nitrile, Flow rate: 1 ml / min, column: 4.6 mm x 250 mm, filler: silica gel coated with silicone polymer, and carbon ratio of 14.0 to 15.5 %, The retention time of which is about 21 minutes when separated by octadecyl group) or its equivalent (compound 3).
  • silica gel ram eluent: a mixed solvent of n-hexane and ethyl acetate
  • HPLC mobile phase:
  • Nos. 3 to 3 can be isolated from plants using, for example, the method described in Phytochemistry, vol. 32, No. 2, p357-363, 1993 (author: Akiko Jitoe, Toshiya Masuda, and Nobuji Nakatani). Can be.
  • the extract obtained by extraction under heating for example, from 30 to 100 ° C.
  • filtration may be used as it is, but may be concentrated or dried under reduced pressure if necessary.
  • a thing may be used.
  • these extracts or extracts can be fractionated and purified using, for example, silica gel column chromatography, and used.
  • the extraction solvent is not particularly limited.
  • examples of the extraction solvent include water, methyl alcohol, polyethyl alcohol, and the like.
  • Lower phenolic esters such as ethyl acetate, benzene, and toluene
  • aromatic hydrocarbons such as hexane, heptane, petroleum ether, etc., ethers such as ethyl ether, methyl ether, etc., ketones, such as acetone, methyl ethynoleketone, etc.
  • a method using a known solvent such as a halogen solvent such as rolo-honolem or dicopene is used, and these solvents can be used alone or in combination of two or more.
  • Preferred extraction solvents include water, an aqueous solution of ethyl alcohol, and an aqueous solution of 1,3-butylene glycol.
  • an extract containing these as an active ingredient can also be used.
  • an extract include a crude fraction obtained by subjecting a primary extract extracted with the above-mentioned extraction solvent to a crude purification by silica gel mouth chromatography or the like.
  • the PAF antagonist of the present invention may be used in addition to a skin external preparation composition for preventing and / or improving skin roughness, and a PAF-related disease, for example, a inflammatory keratinizing disease. It can be applied to amelioration and prevention of symptoms such as atopic dermatitis, contact dermatitis and eczema, which are allergic skin diseases.
  • PAF is one of the lipid mediators produced by the action of metabolic enzymes such as phospholipase acetyltransferase from phospholipids of cell membranes, and mainly inflammatory cells such as mast cells, neutrophils and monocytes. Produced in PAF has been reported to be involved in inflammation and allergic eosinophil migration, inflammatory cytokine production, cell proliferation, differentiation, and apoptosis.
  • PAF antagonists are antagonistic to PAF By inhibiting the binding to its receptor, it is effective in ameliorating or preventing diseases and symptoms associated with PAF.
  • Production Example 3 Extraction of crude fraction containing compound 1 and compound 2 as active ingredients
  • the methanol extract of the plant of the genus Zingiberaceae is fractionated on a silica gel column (eluent: a mixed solvent of n-hexane and ethyl acetate), and then a reversed-phase open column. (Eluent: mixed solvent of methanol and water), and the obtained fraction is subjected to CAPCELL PAK C18 UG 120A manufactured by Shiseido Co., Ltd.
  • FIG. 2 shows 13 C-NMR and FIG. 3 shows i H-NMR of Compound 3, respectively.
  • Compound 1, Compound 2 and Compound 3 of the present invention have excellent PAF antagonistic activity, and are useful for improving and preventing diseases and symptoms associated with PAF. Applicable as an AF antagonist. It can also be added as an active ingredient of a skin external preparation composition for preventing and improving skin roughness.
  • PAF is one of the lipid mediators produced from the phospholipids of the cell membrane by the action of metabolic enzymes such as phospholipase-diazetyltransferase, and is mainly used for mast cells, neutrophils and monocytes. Produced by inflammatory cells such as spheres. PAF has been reported to be involved in inflammation and allergic eosinophil migration, inflammatory cytokinetic production, cell proliferation, differentiation, and apoptosis. By antagonistically inhibiting the binding to its receptor, it is thought to be effective in improving or preventing diseases and symptoms associated with PAF.
  • Compound 1 and Compound 2 are known substances, they have not been reported to have an excellent PAF antagonistic action, and inflammatory and allergic skin based on the PAF antagonistic action of these compounds. No application to a drug for treating a disease or an external preparation composition for improving skin roughness is known at all.
  • the compounding amount of Compounds 1, 2 and Z or 3 is 0.001 to 20.0% by weight, preferably 0.01% by weight of the total amount of the external preparation composition. to 1 0. 0 weight 0/0. If it is 0.0 0 less than 1 wt 0/0, the effect in the present invention is not sufficiently exhibited, also increased further effect though the amount is more than 2 0.0 wt% to not expect virtually It tends to be difficult to incorporate the composition into a skin external preparation composition.
  • the skin external preparation composition of the present invention contains components commonly used in skin external preparations such as cosmetics and pharmaceuticals, for example, whitening agents, moisturizing agents, antioxidants, oily components, and ultraviolet absorption.
  • components commonly used in skin external preparations such as cosmetics and pharmaceuticals, for example, whitening agents, moisturizing agents, antioxidants, oily components, and ultraviolet absorption.
  • Agents, surfactants, thickeners, alcohols, powder components, coloring materials, aqueous components, water, various skin nutrients, and the like can be appropriately compounded as necessary.
  • composition for external use on skin of the present invention further comprises sodium edetate and edeate.
  • Sequestering agents such as sodium tritonate, sodium citrate, sodium polyphosphate, sodium metalate, dalconic acid, quinic acid, glycolic acid,
  • Various plants such as lactic acid, salicylic acid, sodium sulfite, caffeine, tannin, pantothenic acid and its derivatives, nicotinic acid and its derivatives, tranexamic acid and its derivatives, licorice extract, glabridin, malonier, and escin Extracts, vitamin E derivatives such as vitamin E and tocopherol acetate, drugs such as dalycyrrhizic acid and its derivatives or salts thereof, placental extracts, magnesium ascorbic acid and magnesium asconolevate, Ascorbic acid derivatives such as asconolevic acid gnorecoside, arbutin, kojic acid, ellagic acid, potato bean oil, Whitening agents such as 4-n-
  • the skin external preparation composition of the present invention refers to pharmaceuticals, quasi-drugs, and cosmetics, and is blended with conventional skin external preparation compositions such as ointments, creams, emulsions, lotions, packs, and bath preparations. Any form can be used, and the dosage form is not particularly limited.
  • the human blood was centrifuged at room temperature for 20 minutes at 100 rpm to collect platelet-rich plasma (PRP), and then centrifuged at 3000 rpm for 5 minutes to collect platelet-poor plasma (PPP). After pre-warming PRP223L at 37 ° C, add 2 / z L of a test substance or solvent at a predetermined concentration, incubate at 37 ° C for 2 minutes, and then agglutinate-inducing substance PAF. 25 ⁇ L was added.
  • PRP platelet-rich plasma
  • PPP platelet-poor plasma
  • the induced aggregation was measured using an aggregometer (MCM Hematracer MCM Medical Co., Ltd.), and the maximum agglutination rate of the test sample was compared with the solvent control group to determine the PAF antagonistic effect of the test substance. Was evaluated. The results are shown in Table I.
  • the plants of the family Ginga (Zing iberaceae), which are already known to be applied to rough skin, are Indonesian name: Kuny 11, name: Shircuma domes ti ca and (, Zing ibera ceae)
  • An ethanol extract of the family Nolemupyang (Lempuyang, scientific name: Zingi ber aromaticum Val.), and chickpeas (scientific name: Isodon japonicus H ara), which is known to have PAF antagonism Was tested. Table I also shows the results.
  • PAF antagonism was evaluated by its inhibitory effect on platelet aggregation by PAF.
  • the induced agglutination was measured using an aggregometer (MCM Hematracer MCM Medical Co., Ltd.), and the maximum agglutination rate of the test sample (from the agglutination curve of the test sample with the PPP value of 100). Of the test substance by comparing the maximum was evaluated for its inhibitory effect on PAF-induced platelet aggregation. The results are shown in Table III.
  • the effect of the skin external preparation composition according to the present invention by the skin application was evaluated based on the improvement rate against rough skin (erythema / desquamation, dryness, eczema, itching) and loss of power razors, and skin irritation. Twice a day, using the face of a panel of 60 women suffering from rough skin, using the composition (% by weight) shown in Table m in one of the left and right samples and the control in the other sample After 2 weeks, the skin condition was visually evaluated. Immediately after shaving, a lotion of the composition shown in Table 1 was applied to 30 male panels losing force razors, and the effect on losing force razors was determined. Each criterion was as follows.
  • ⁇ The ratio (effective rate) at which the subject showed significant, effective and somewhat effective (effective rate) was 80% or more.
  • ⁇ The proportion of subjects who show significant, effective, and somewhat effective (effective rate) is 50 % To less than 80%.
  • ⁇ The ratio (effective rate) at which the subject shows a significant effect, an effective effect, and a somewhat effective effect is 30% or more and less than 50%.
  • X The proportion (effective rate) in which the subjects show a significant effect, an effective effect, and a somewhat effective effect is less than 30%.
  • ⁇ ⁇ The percentage of subjects with skin irritations exceeded 0% and was less than 5%.
  • ⁇ The percentage of subjects with skin irritation was 5% or more and less than 10%.
  • X The proportion of subjects with a burning sensation on the skin was 10% or more.
  • ⁇ The ratio (effective rate) at which the subject shows a markedly effective, effective and slightly effective (effective rate) is 8 0% or more.
  • the proportion (effective rate) at which the subject shows a markedly effective, effective and somewhat effective (effective rate) is 50% or more to less than 80%.
  • ⁇ The percentage of the subject showing significant, effective and somewhat effective (effective rate) is 30% or more to less than 50%.
  • a razor is slightly weaker.
  • ⁇ The percentage of the subjects showing significant, effective and somewhat effective (effective rate) is 80% or more.
  • the proportion (effective rate) at which the subject shows a markedly effective, effective and somewhat effective (effective rate) is 50% or more to less than 80%.
  • ⁇ The proportion (effective rate) at which the subject shows a significant effect, an effective effect, and a somewhat effective effect is from 30% to less than 50%.
  • ⁇ The proportion of subjects who felt burning on the skin was less than 10%.
  • X The proportion of subjects with a burning sensation on the skin was 10% or more.
  • a skin roughness improvement effect test was performed on a human body panel. That is, the skin surface morphology of a healthy female person (face) was sampled using a replica method and observed under a microscope (17 ⁇ ). The skin roughness evaluation was judged to be 1 or 2 based on the criteria shown in Table V based on the skin crest state and the peeling state of the stratum corneum (rough skin panel). The lotions of products 1 and 2 and comparative products 1 and 2 were applied twice a day for 2 weeks. Two weeks later, the skin condition was observed again according to the replica method described above, and evaluated according to the criteria in Table V. The results are shown in Table VI.
  • the lotion of the product of the present invention exhibited a remarkable skin roughness improving effect as compared with the lotion of the comparative product.
  • Test example 3 Actual use test by replica method
  • the surface morphology of the skin of a healthy female (face) was sampled using a replica method and observed under a microscope (17 times). Panels whose skin roughness was judged to be 1 or 2 based on the criteria shown in Table VII based on the state of the skin pattern and the peeling state of the stratum corneum (rough skin panels) ⁇ 5 and control lotions were applied twice a day for 2 weeks. Two weeks later, the skin condition was observed again according to the replica method described above, and evaluated according to the criteria shown in Table W. Table M shows the results.
  • the replica method In the case of the replica method, the present invention has a remarkable effect of improving skin roughness as compared with the control solution. Demonstrated.
  • soap powder and borax to ion-exchanged water, heat and dissolve, and maintain at 70 ° C (aqueous phase). Mix the other ingredients, heat and melt, and keep at 70 ° C (oil phase). The oil phase is gradually added to the aqueous phase while stirring to carry out the reaction. After the reaction is completed, emulsify uniformly with a homomixer, and after cooling, stir well and cool to 30 ° C.
  • phase A Dissolve the carboxybutyl polymer in a small amount of ion-exchanged water (phase A).
  • phase A Add poly (ethylene glycol) 1500 and triethanolamine to the remaining ion-exchanged water, dissolve by heating, and maintain at 70 ° C (aqueous phase). Mix with other components, heat and maintain at 70 ° C (oil phase).
  • oil phase to the aqueous phase, perform pre-emulsification, add the A phase, uniformly emulsify with a homogenizer, cool to 30 ° C with good stirring after emulsification.
  • Example 8 _pack
  • phase A Dissolve phase A, phase B and phase C uniformly, and add phase B to phase A for solubilization. Next, this is added to the C phase and then filled.
  • Example 10 Emulsion type foundation (cream type)
  • Titanium dioxide 10.3 Sericite 5.4 Kaolin 3.0 Yellow iron oxide 0.8 Bengala 0.3 Black iron oxide 0.2
  • Decamethinolecyclopentasiloxane 11.5 Liquid paraffin 4.5 Polyoxyethylene-modified dimethylpolysiloxane 4.0 (Aqueous phase)
  • a cream was prepared according to the following formulation.
  • the preparation method was as follows: ion-exchanged water was dissolved by adding propylene glycol and ethylenediaminetetraacetate sodium salt, and kept at 70 ° C (aqueous phase). The other components were mixed and heated to dissolve and maintained at 70 ° C (oil phase). The oil phase was gradually added to the aqueous phase, pre-emulsified at 70 ° C, and uniformly emulsified with a homomixer. Thereafter, the mixture was cooled to 30 ° C while stirring well.
  • soap powder and borax to ion-exchanged water, dissolve by heating, and maintain at 70 ° C (aqueous phase). Mix the other ingredients, heat and melt, and keep at 70 ° C (oil phase). The oil phase is gradually added to the aqueous phase while stirring to carry out the reaction. After the reaction is completed, homogenize uniformly with a homomixer. After emulsification, cool to 30 ° C while stirring well.
  • Vaseline 5 0 Liquid paraffin 10.0 Polyoxyethylene (10 mol)
  • phase A Dissolve the carboxyvinyl polymer in a small amount of ion-exchanged water (phase A).
  • phase A Add polyethylene glycol 1500 and triethanolamine to the remaining ion-exchanged water, dissolve by heating, and maintain at 70 ° C (aqueous phase). Mix with other ingredients, heat and maintain at 70 ° C (oil phase).
  • oil phase to water phase, pre-emulsify, add phase A, homogenize homogeneously with homomixer, cool to 30 ° C with good stirring after emulsification.
  • Carboxybulmer 0 2 (Trade name: Carboponore 940, BFGoodrich Chemical Company) Purified water residue
  • phase A and phase C Dissolve phase A and phase C uniformly, and add phase A to phase C for solubilization. Then, after adding phase B, filling is performed.
  • phase A Dissolve phase A, phase B and phase C uniformly, and add phase B to phase A for solubilization. Next, this is added to the C phase and then filled.
  • Example 20 Emulsion type foundation (cream type)
  • a cream was prepared in the same manner as in Example 12 using the following formulation.
  • propylene glycol and ethylenediaminetetraacetic acid trisodium salt were added and dissolved, and kept at 70 ° C (aqueous phase).
  • the other components are mixed and dissolved by heating and kept at 70 ° C (oil phase).
  • the oil phase is gradually added to the aqueous phase, pre-emulsified at 70 ° C, and homogenized with a homomixer. After emulsification, the mixture was cooled to 30 ° C while stirring well.
  • soap powder and borax to ion-exchanged water, dissolve by heating, and keep at 70 (aqueous phase). Mix with other ingredients, heat and melt to keep at 70 ° C (oil phase ). The oil phase is gradually added to the aqueous phase while stirring to carry out the reaction. After the reaction is completed, emulsify uniformly using a homomixer. After emulsification, cool to 30 ° C while stirring well.
  • Propylene glycol was added to the ion-exchanged water and heated to 70 ° C (aqueous phase), while other components were mixed and heated and melted to 70 ° C (oil phase). Next, while stirring the oil phase, the aqueous phase was gradually added to the mixture, and the mixture was uniformly emulsified with a homomixer. After the emulsification, the mixture was cooled to 30 ° C while stirring well.
  • the powdery components of talc and black iron oxide were sufficiently mixed with a blender, and the oily components of squalane and isocetyl octanoate, compound 1, preservative, and fragrance were added, kneaded well, and the mixture was filled into a container and molded.
  • Example _30 Emulsion type finish (cream type)
  • a powder portion sufficiently mixed and pulverized was added thereto and subjected to a homomixer treatment. Further, the oil phase mixed by heating was added thereto, and the mixture was subjected to a homomixer treatment. Then, a fragrance was added with stirring and the mixture was cooled to room temperature.
  • Preservative B Water phase
  • phase A and the aqueous phase of phase B Heat the oil phase of phase A and the aqueous phase of phase B to 70 ° C, respectively, and completely dissolve them. Add phase A to phase B and emulsify with an emulsifier. The emulsion was cooled using a heat exchanger to obtain a cream.
  • the carboxybutyl polymer was dissolved in a small amount of ion-exchanged water (phase A).
  • Phase A Polyethylene dalicol 150 and triethanolamine are added to the remaining ion-exchanged water, heated and dissolved, kept at 70 ° C (aqueous phase), mixed with other components, heated and melted to 70 ° C. Kept at C (oil phase).
  • the oil phase was added to the aqueous phase, pre-emulsified, the phase A was added, and the mixture was uniformly emulsified with a homomixer. After the emulsification, the mixture was cooled to 30 ° C while stirring well.
  • Phase A and phase C were each dissolved uniformly, and phase A was added to phase C for solubilization. Then, after the phase B was added, the mixture was filled.
  • Phases A, B and C were each dissolved uniformly, and phase A was added to phase B to solubilize. Next, this was added to the C phase and then filled.
  • Example 35 Solid Foundation
  • the powdery components of talc and black iron oxide were sufficiently mixed in a blender, and the oily components of squalane and isosetyl octanoate, compound 2, preservative, and fragrance were added, kneaded well, and the mixture was filled into a container and molded.
  • Example 36 Emulsion type finish _ (cream type)
  • a powder portion sufficiently mixed and pulverized was added thereto and subjected to a homomixer treatment. Further, the oil phase mixed by heating was added thereto, and the mixture was subjected to a homomixer treatment. Then, a fragrance was added with stirring and the mixture was cooled to room temperature.
  • phase A and phase C Dissolve phase A and phase C uniformly, and add phase A to phase C for solubilization. Then, after the phase B was added, the mixture was filled.
  • Phases A, B and C were each dissolved uniformly, and phase B was added to phase A to solubilize. Next, this was added to the C phase and then filled.
  • Example 40 Lotion
  • the ⁇ ⁇ ⁇ ⁇ ⁇ ⁇ phase alcohol phase was added to the ⁇ phase aqueous phase and solubilized to obtain a lotion.
  • the alcohol phase of phase A was added to the aqueous phase of phase B and solubilized to obtain a lotion.
  • phase A The oil phase of phase A and the aqueous phase of phase B were each heated to 70 ° C and completely dissolved.
  • Phase A was added to Phase B and emulsified with an emulsifier.
  • the emulsion was cooled using a heat exchanger to obtain an emulsified foundation.
  • the present invention is excellent in PAF antagonism, and is expected to exhibit an excellent effect in amelioration and prevention of inflammatory and allergic diseases based on PAF antagonism.
  • the external preparation composition for preventing and improving skin roughness according to the present invention is excellent in skin roughness improvement effect, and has excellent effects in improvement and prevention of various skin diseases, skin roughness, roughness, etc., and safety. It is also excellent.

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Abstract

L'invention concerne des antagonistes du facteur d'activation des plaquettes (PAF), et des compositions dermatologiques destinées à un usage externe et servant à empêcher ou réparer les gerçures de la peau. Ces antagonistes contiennent, en tant que principe(s) actif(s), un extrait de Bengle (plante appartenant à l'espèce zingiber de la famille des zingiberaceae ou les composés des formules (1) et/ou (2) contenant lesdits antagonistes.
PCT/JP2000/007601 1999-10-27 2000-10-27 Antagonistes du facteur d'activation des plaquettes et compositions dermatologiques destinees a un usage externe contenant lesdits antagonistes WO2001030367A1 (fr)

Applications Claiming Priority (6)

Application Number Priority Date Filing Date Title
JP11/305496/ 1999-10-27
JP30549699 1999-10-27
JP2000309061A JP2001192339A (ja) 1999-10-27 2000-10-10 血小板活性化因子拮抗剤
JP2000-309061 2000-10-10
JP2000-321801 2000-10-20
JP2000321801 2000-10-20

Publications (1)

Publication Number Publication Date
WO2001030367A1 true WO2001030367A1 (fr) 2001-05-03

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PCT/JP2000/007601 WO2001030367A1 (fr) 1999-10-27 2000-10-27 Antagonistes du facteur d'activation des plaquettes et compositions dermatologiques destinees a un usage externe contenant lesdits antagonistes

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WO (1) WO2001030367A1 (fr)

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2003090708A1 (fr) * 2002-04-23 2003-11-06 Shiseido Co., Ltd. Preparation externe pour la peau
WO2007113698A3 (fr) * 2006-03-03 2008-01-03 Csir Traitement préventif et rémission de maladies allergiques
CN108484373A (zh) * 2018-05-23 2018-09-04 中国科学院昆明植物研究所 一个具有促胶原蛋白分泌功效的化合物及其应用

Non-Patent Citations (5)

* Cited by examiner, † Cited by third party
Title
BUKHTIAR H. SHAH ET AL.: "Inhibitory effect of curcumin, a food spice from turmeric, on platelet activating factor and arachidonic acid mediated platelet aggregation through inhibition of throboxane formation and Ca2+ signaling", BIOCHEMICAL PHARMACOLOGY, vol. 58, 1999, pages 1167 - 1172, XP002936339 *
MASANORI KUROYANAGI ET AL.: "Further characterization of the constituents of a thai medicinal plant, zingiber cassumunar Roxb.", CHEM. PHARM. BULL., vol. 28, no. 10, 1980, pages 2948 - 2959, XP002936338 *
MITSURU HOTTA: "Useful Plants of the World", 25 August 1989, HEIBONSHA, XP002936335 *
THANOMWANG AMATAYAKUL ET AL.: "Chemistry and crystal structures of some constituents of zingiber cassumunar", AUST. J. CHEM., vol. 32, no. 1, 1979, pages 71 - 88, XP002936337 *
TOSHIYA MASUDA ET AL.: "Antioxidative and antiinflammatory compounds from tropical ginger: Isolation, structure determination and activities of cassumunins a, b, and c, new complex curcuminoids from zingiber cassumunar", J. AGRIC. FOOD CHEM., vol. 42, no. 9, 1994, pages 1850 - 1856, XP002936336 *

Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2003090708A1 (fr) * 2002-04-23 2003-11-06 Shiseido Co., Ltd. Preparation externe pour la peau
WO2007113698A3 (fr) * 2006-03-03 2008-01-03 Csir Traitement préventif et rémission de maladies allergiques
US8158165B2 (en) 2006-03-03 2012-04-17 Csir Preventative treatment and remission of allergic diseases
CN108484373A (zh) * 2018-05-23 2018-09-04 中国科学院昆明植物研究所 一个具有促胶原蛋白分泌功效的化合物及其应用

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