JP2007077171A - Cathepsin d production promoter - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a production promoter of cathepsin D associated with the abrasion of horny substance at an epidermal cell. <P>SOLUTION: The production promoter of the cathepsin D by the epidermal cell comprises an extract of a plant selected from Schizonepeta tenuifolia Briquet (var.japonica Kitagawa), Saussurea lappa Clarke, Pharbitis nil Choisy, Paeonia lactiflora Pallas, Camellia Sinensis(L) O.Kuntze, Haematoxylon campechianum L., Rehmannia glutinosa Liboschitz var. purpurea Makino or Rehmannia glutinosa Liboschitz, Thymus vulgaris L., Prunus persica Batsch or Prunus persica Batsch var. davidiana Maximowicz, Paeonia suffruticosa Andrews (Paeonia moutan Sims), Zingiber officinale Roscoe, Polygala tenuifolia Willdenow, Plantago asiatica L., Panax japonicum C.A.Meyer, Picrasma quassioides Bennet, Rhus javanica L., Betula platyphylla Sukatchev var.japonicum Hara, Coixlachryma-jobi L.var. ma-yuen Stapf, Hydrangea serrata Seringe var.thunbergii Sugimoto, Arnica Montana L., Arctium lappa L., Ganoclerma lucidum Karst. and Lilium candidum, and one or more kinds selected from lactoferrin. <P>COPYRIGHT: (C)2007,JPO&INPIT

Description

  The present invention relates to a cathepsin D production promoter for epidermal cells.

  Many pathological symptoms of the epidermis are characterized by thick stratum corneum formation and abnormal keratinocyte detachment, such as psoriasis, psoriasis, ichthyosis, dry skin, dull skin, skin aging This is the case. On the other hand, sulfur compounds such as sulfur and selenium disulfide and vitamin A acid are known as agents that promote exfoliation and softening of the keratin, but skin irritation and skin roughness are caused by continuous use of sulfur compounds. Vitamin A acid is not particularly preferable for women in terms of side effects such as teratogenicity, and there is a problem in that skin irritation is also strong. Therefore, development of a drug or cosmetic that promotes exfoliation of keratin from the daily skin care stage, is effective in preventing and treating skin diseases, dull skin, and aging associated with abnormal exfoliation of keratinocytes, and is highly safe for the human body. Is desired.

On the other hand, the epidermis is composed of four layers, from the lower layer to the basal cell layer, spinous cell layer, granule cell layer, and stratum corneum cell layer. Although it exists abundantly, it has been suggested in recent years that digestion of desmosomes by several proteases such as aspartic protease, serine protease, cysteine protease, metalloprotease is involved in exfoliation of keratin (Non-patent Document 1). . Among them, cathepsin D, an aspartic protease derived from lamellar granules in the epidermis, has an optimum pH in the weakly acidic region, which is the pH of the skin (stratum corneum). It is thought that the involvement in is large (non-patent document 2).
Kitajima, Journal of the Japan Cosmetic Science Society, Vol.15, No.4 (1991), 225-230 Kawada et al., Arch. Dermatol. Res., Vol. 289, 87-93, 1997

  An object of the present invention is to provide a cathepsin D production promoter that is involved in exfoliation of keratin in the epidermal cells.

  The inventors of the present invention have studied paying attention to quantitative changes in proteases involved in keratinocyte detachment, and found that certain plant extracts and the like increase the amount of cathepsin D in cultured epidermal cells. Was completed.

  That is, the present invention includes: mussel, mokko, kengoshi, peonies, tea, logwood, elephant, thyme, peach, button, ginger, onji, psyllium, chiketsujinjin, nigaki, gobaishi, birch, yokoinin, amacha, arnika, burdock The present invention provides a plant extract selected from litchi and lily and an epithelial cell cathepsin D production promoter comprising at least one selected from lactoferrin.

  The cathepsin D production promoter of the present invention is highly safe for the human body and promotes exfoliation of the keratin from the daily skin care stage, and aims to prevent and treat skin diseases, dull skin, and aging associated with abnormal exfoliation of keratinocytes. It is useful as a pharmaceutical or cosmetic.

  The plant in the plant extract of the cathepsin D production promoter of the present invention is a cowpea (Calpa ovata G. Don or Catalpa ungei CAMeyer of the genus Caenpasaceae), Kakei (Schizonepeta tenuifoliaBriquet (var.japonica Kitagawa)) , Mokko (Asteraceae Saussurea lappa Clarke), Kengoshi (Convolvulaceae Pharbitis nil Choisy), Peonies (Peonyaceae Paeonia lactiflora Pallas or other related plants), Cha (Camellia Sinensis (L) O. Kuntze), carrot (Panthax ginseng CAMeyer), logwood (Haematoxylon campechianum L.), scorpion (Rhinocephalus Rehmannia glutinosa Liboschitz var. Purpurea Makino or Rehmannia glutinosa Libosch) Thymus vulgaris L.), Peach (Rosaceae Prunus persicaBat) sch, or Prunus persica Batsch var. Plant), ginger (Zingiber officinale Roscoe), Onji (Polygala tenuifolia Willdenow), psyllium (Planetago asiatica L.), prickly pear anax CAMeyer), oysters (Pyracrasma quassioides Bennet), gobishi (Rhus javanica L.), birch (Betula platyphylla Sukatchev var.japonicum Hara) Cnidium officinale Makino), Yokuinin (Coixlachryma-jobi L.va) m. Ganoclerma lucidum Karst.) And lilies (Lilium candidum).

  The parts of these plants are: oxen berries, pearl oysters, mokko roots, kengoshi seeds, peonies roots, tea leaves, roots excluding carrot fine roots, logwood timbers, diaus roots Above-ground part, peach seed, button root bark, apricot seed, ginger rhizome, Onji root, psyllium ground part, chixet carrot root, oyster xylem, gobishi gall (insect bug), birch Bark and xylem, nematode rhizomes, seeds excluding Yakuinin seed coat, leaves and branches of shoots, arnica flowers, burdock roots, litchi fruiting bodies and lily bulbs are preferred. Moreover, it can be obtained as a concentrated extract or a dry powder by immersing or heating under reflux with an appropriate extraction solvent, and filtering, concentrating and lyophilizing as appropriate.

  As extraction solvents, commonly used organic solvents such as methanol, ethanol, propanol, butanol, ether, ethylene glycol, propylene glycol, butylene glycol, hexane, heptane, cyclohexane, ethyl acetate, acetone, toluene, dichloroethane, chloroform, and water 1 type of these can be used individually or in mixture of 2 or more types. Among these solvents, polar solvents are preferable, and ethanol, water, propylene glycol, and butylene glycol are particularly preferable.

  The extraction treatment can usually be carried out at a temperature of about 3 to 100 ° C. for several hours to several weeks by a conventional method. Separation and purification of the active ingredient from the extract is performed by gel filtration, column chromatography, precision distillation of the extract. Etc.

  In addition, lactoferrin, which is an active ingredient of the cathepsin D production promoter of the present invention, refers to a mild and nonspecific antibacterial activity protein contained in breast milk or tears, and its origin is not particularly limited. Preferred is milk obtained from mammals such as humans, or non-fat milk obtained by processing these milks, whey, etc. obtained by separation by ion exchange chromatography or the like.

  The plant extract and lactoferrin of the present invention thus obtained promote the production of cathepsin D, which is a protease derived from lamellar granules of epidermal cells, as shown in the Examples. Therefore, the preparation containing the cathepsin D production promoter of the present invention promotes exfoliation of the stratum corneum, and a pharmaceutical or cosmetic for the purpose of preventing and treating skin diseases, dull skin, and aging associated with abnormal exfoliation of corneocytes. Useful as.

  When the cathepsin D production promoter of the present invention is blended as a medicine, it can be used as tablets, capsules, ointments, liquids, extracts, lotions, emulsions, etc. Among them, use as an external medicine is preferable. For example, in the case of an ointment, it may be one based on an oily base, or one based on an oil-in-water or water-in-oil emulsified base. Examples of oily bases include: Examples include vegetable oils, animal oils, synthetic oils, fatty acids and natural or synthetic glycerides.

  In addition, other medicinal components such as analgesic / anti-inflammatory agents, bactericidal / disinfectant agents, astringents, emollients, hormone agents, and the like can be appropriately added to the medicine as necessary.

  When formulated as a cosmetic, in addition to the active ingredients of the present invention, oils, surfactants, UV absorbers, whitening agents, alcohols, chelating agents, pH adjusters, antiseptics that are commonly used as cosmetic ingredients Agents, thickeners, pigments, fragrances, various skin nutrients, and the like can be combined in any combination.

  Cosmetics may be in various forms, for example, water-in-oil or oil-in-water emulsified cosmetics, creams, gels, cosmetic emulsions, lotions, oily cosmetics, facial cleansers, foundations, packs, and the like. it can.

  Although the compounding quantity of the active ingredient in a pharmaceutical or cosmetics is not specifically limited, 0.01 to 20 weight% of the whole composition is normally preferable as a dried material, and 0.1 to 10 weight% is especially preferable.

Production Example 1 Preparation of Kengoshi Extract To 10 g of Kengoshi (Pharbitis nil Choisy, Convolvulaceae) seeds, add 100 mL of a mixture of water and ethanol (50:50) and extract at 50 ° C. with occasional stirring for 5 hours, followed by filtration. did. This was left to stand at 5 ° C. for 7 days for aging, and the resulting sediment and precipitate were filtered. To this was added a mixture of water and ethanol (50:50) to make a total of 100 mL.

Production Example 2
According to Production Example 1, 100 mL of various extracts shown in Table 1 were prepared. Moreover, lactoferrin S FREE (made by Ichimaru Falcos Co., Ltd.) was used as lactoferrin.

Example 1 Cathepsin D production promoting action of cultured epidermal cells Various extracts obtained from Production Examples 1 and 2 of normal and human epidermal cells (Kyokuto Pharmaceutical) at 0.1 and 1.0% concentrations (addition concentration of extract) Cathepsin D, a lamellar granule-derived protease released in the medium, was detected by Western blotting, and the intensity of the band was compared with that of the control. The results are shown in Table 2 as the average of 3 trials.

Claims (1)

  From mussels, mokko, kengoshi, peonies, tea, logwood, ziwo, thyme, peach, buttons, ginger, onji, psyllium, chiketsujinjin, nigaki, gobishi, birch, yokuinin, amacha, arnica, burdock, litchi and lily A plant epithelial cell cathepsin D production promoter comprising at least one selected from plant extracts and lactoferrin.