(1) (1)200407154 玖、發明說明 發明所屬之技術領域 本發明係關於一種促進細胞活性之外用劑，其具有改 善主要以花粉症或口內炎等各疾病之效果，且同時可應用 對細胞的電解質平衡、滲透壓平衡而將細胞活性化’進而 改善皮膚細胞的細胞功能降低所引起的各疾病。 先前技術 過去廣泛使用氯化鈉等無機鹽、葡萄糖等天然糖、或 血漿等作爲各種化粧品或醫藥外用劑之配合劑。例如，有 關含有氯化鈉等柔軟肌膚的乳霜者，已記載於 U.S.P.35 74 854號公報中，另一方面，含於礦物鹽類的皮 膚淸潔用品之申請案已於西德專利公開案第33 27840號說 明書中被記載。且，有關混合葡萄糖對皮膚有潤滑作用的 糖成分之申請案已於U.S.P.3859436號公報中記載。又， 有關刮鬍子用的糊精水溶液之申請案已於U.S.P. 3 777 5 97 號公報中記載。 然而，這些過去的外用劑既使可達到皮膚殺菌及保護 皮膚的目的，但難以改善皮膚毛細管循環及功能降低所引 起的皮膚疾病、及色素沈澱、足癬、股癬、髮癬菌病、狐 臭、脫髮症、頭皮屑、癢等的皮膚細胞分裂功能降低所引 起的各種疾病。 因此，本發明者發現以活性化皮膚細胞，而改善因皮 膚細胞的細胞功能降低所引起的各疾病者，其爲於皮膚表 -6- (2) (2)200407154 面做出與皮膚細胞間質液相同的環境，應用電解質平衡、 滲透壓平衡進而發現可促進連皮膚表面亦可促進障礙細胞 正常化的水性皮膚及毛髮化粧品（專利第1 597430號）。 故，該水性皮膚及毛髮化粧品可達到，對於褐斑、紅 臉時以刺激皮下細胞使其分裂進而治療，又對頭皮、狐臭 等則經滲透壓作用而刺激毛母細胞而促進發毛及脫臭作用 之效果。即，該水性皮膚及毛髮化粧品可得到對脫毛症而 言治療率爲8 3 %，對於色素沈澱之治療率爲9 5 %，對於 紅臉的治療率爲5 3 %之效能結果。 然而，這些效能主要對於皮膚或毛髮則無顯著的效 果，該發明者想到如皮膚細胞等的活性化，於無副作用下 可使黏膜細胞活性化，故對於口腔黏膜疾病所引起的口內 炎、或鼻黏膜障礙所引起的花粉症等疾病亦可能有效而進 行硏究。 因此該發明者便發明一種促進細胞活性外用劑，其既 使作爲口腔或鼻黏膜的外用劑使用亦無副作用的顧慮，例 如可適用於如口內炎或花粉症等較廣範圍的細胞而言之各 疾病（專利第268 1 527號）。該促進細胞活性之外用劑係 添加糊精等多醣類或葡萄糖、木糖、香菇多醣等者。該促 進細胞活性之外用劑可得到對口內炎爲治療率1 〇 〇 %，對 花粉症爲治療率100%之優良結果。 發明內容 然而，對前述的促進細胞活性之外用劑所顯示的對花 (3) (3)200407154 粉症之治療率，於當時僅以40人爲對象時所顯示者，其 後隨著花粉症的患者急速增加，花粉症的治療率有漸漸降 低之傾向。即，已知對於前次（平成2年）的效能試驗 中，對花粉症顯示100%有效率者，其後經過數十年的現 今，有效率與發病率的爆發性增加成反比而急速地下降。 花粉症的發病原因雖未明確，但推測爲因個人因素對口腔 或鼻黏膜等細胞有某種影響而誘發該疾病。因此，可推測 欲提高口腔或鼻黏膜等免疫力或痊癒能力，必須保持細胞 組織的健康狀態，防止各因素造成的壞影響，可抑制急速 增加的花粉症之發病，同時亦具有治療效果。 本發明提供一種更改良之先前發明的促進細胞活性之 外用劑爲目的，其可提高口腔或鼻黏膜等免疫力或痊癒能 力，且無副作用之顧慮，可適用於除花粉症或口內炎以外 的皮膚或頭皮等廣範圍的細胞級之各疾病。 欲達成上述目的的本發明第1方法爲，將多醣體溶解 於水溶液之促進細胞活性之外用劑，對全體而言添加重量 比爲，1〜50%的木葡聚醣、1〜50%的昆布多醣、與1〜 50%的多醣體K(krestin)者。 第2方法爲，溶解該多醣體的水溶液中，對全體而言 含有重量比爲，1〜50%的果膠、1〜30%的糊精、1〜30 %的葡萄糖、1〜40%的支鏈澱粉、1〜3〇%的香菇多醣、 1〜5〇%的環糊精與1〜50%的海藻糖者。 第3方法爲，溶解該多醣體的水溶液中，對全體而言 添加重量比爲，0. 1〜1的氯化鈉、0. 1〜1 %的氯化鈣、與 -8 - (4) (4)200407154 0 . 1〜1 %的氯化鉀者爲解決課題的方法。 有關人類皮膚上病變的發炎、色素沈澱、脫毛等各種 症狀，其原因與紫外線、化學物質等種種因素有關，其僅 限於細胞級的變化，具體而鹽爲細胞內小器官之一的粒線 體之膜或細胞膜障礙而言。即，粒線體的膜障礙引起細胞 內呼吸阻礙，進而降低細胞動力來源之 ATP (腺苷三磷 酸）的產生。因如此ATP的不足引起細胞膜能量運輸功 能的下降，而降低細胞與間質液間的物質輸送能力。結果 產生細胞內的葡萄糖等營養物質的不足，引起ATP酸性 降低之所引發的血液循環不佳。 產生如上述細胞級下的變化之原因有許多，特別爲對 口腔或鼻黏膜等細胞而言，經滲透壓作用而增加細胞間質 液，使疾病部位的細胞活性化。且，得知藉由木葡聚醣、 昆布多醣、與多醣體K的添加，可提高口腔或鼻黏膜等 細胞組織的免疫力或痊癒力。 實施方式 本發明基本配合爲將多醣體溶解於水溶液之促進細胞 活性之外用劑，對全體而言添加重量比爲，1〜50 %的木 葡聚醣、1〜50%的昆布多醣、與 1〜50%的多醣體K (krestin)者 ° 木葡聚醣爲普遍存在於伸長•肥大的植物細胞之細胞 壁（一次壁）的組成糖鏈。植物種類的特異性係因木糖殘 基由半乳糖或岩藻糖-半乳糖鍵結所產生。該半乳糖殘基 -9 - (5) (5)200407154 及岩藻糖殘基雖分別可與植物凝血素鍵結，但對這些分枝 糖鏈的功能則未知。植物細胞的成長，係經由來自細胞所 具有的滲透壓之吸水現象而產生，吸水力則由細胞壁的鬆 驰引起壁壓減少所產生。該細胞壁的鬆弛雖未知，但細胞 的伸長常會引起木葡聚醣的分解與可溶化，作爲管理細胞 生理活性的多醣類之一而受注目。 昆布多醣被分類爲碳水化合物之一的/5葡聚醣之昆布 多醣，係含有以香菇爲主的覃類或昆布等之海草類者，其 具有提高免疫力的效果。已知單獨時難以吸收，必須與蛋 白質一起攝取較佳。 多醣體K(kfestin)係使用於作爲增強人類癌細胞的 HLA等級I抗原的表現之免疫治療醫藥劑，係由河原蕈菌 絲體所萃取出。該多醣體K已被確認具有對胃癌、結 腸·直腸癌、小細胞肺癌等腫瘤性疾病之免疫治療作用。 發明者由多數的多醣類中，硏究適用於外用劑的成 分，結果調製出組合這些木葡聚醣、昆布多醣、多醣體 K，而提高口腔或鼻黏膜等的細胞組織之免疫力或痊癒力 的外用劑。 這些多醣體溶解於水溶液中，預先對全體而言含有重 量比爲，1〜50%的果膠、1〜30%的糊精、1〜30%的葡 萄糖、1〜30%的香菇多醣、1〜50%的海藻糖者。 果膠作爲植物細胞壁的結構成分之纖維素等，經由與 其他成分結合而可進行植物細胞相關作用。具有膠體化作 用之成分可適用於本發明外用劑之添加劑。 -10- (6) 200407154 又，溶解多醣體的水溶液中，添加氯化鈉、氯化鈣與 氯化鉀。氯化鈉的配合量對皮膚有滲透性平衡、電解質平 衡之有效性，即，欲活性化皮膚細胞，對全體而言將重量 比爲0. 1〜1%，同樣地對各氯化鈣與氯化鉀亦爲0. 1〜1 %溶解於水相成分中。 【實施例】 其次，處方例1 的效果由表1所 -處方例1 - 糊精 18 葡萄糖 10 環糊精 2 海藻糖 3 支鏈澱粉 7 香菇多醣 7 昆布多醣 2 多醣體K 1 果膠 3 木葡聚醣 1 氧化鈉 0.9 氯化鈣 0.3 氯化鉀 0.3 純水 44.5 計 重量比（％) 100(1) (1) 200 407 154 玖 Description of the invention The technical field to which the invention belongs The present invention relates to an external agent for promoting cell activity, which has the effect of improving various diseases such as hay fever or endostomatitis, and can also be applied to The cell's electrolyte balance and osmotic pressure balance will activate the cells, thereby improving various diseases caused by the reduction of cell functions of skin cells. Prior art In the past, inorganic salts such as sodium chloride, natural sugars such as glucose, and plasma were widely used as complexing agents for various cosmetic or pharmaceutical external agents. For example, those who contain soft skin creams such as sodium chloride are described in USP 35 74 854. On the other hand, applications for skin cleansers containing mineral salts have been published in the West German Patent It is described in No. 33 27840. Further, an application concerning a sugar component having a lubricating effect on the skin by mixing glucose has been described in U.S.P. 3859436. In addition, an application concerning an aqueous dextrin solution for shaving is described in U.S.P. 3 777 5 97. However, even if these past external preparations can achieve the purpose of skin sterilization and skin protection, it is difficult to improve skin diseases caused by skin capillary circulation and reduced function, and pigmentation, athlete's foot, jock itch, ringworm, and odor , Hair loss, dandruff, itching and other diseases caused by reduced skin cell division. Therefore, the present inventors have discovered that by activating skin cells and improving various diseases caused by a decrease in the cell function of the skin cells, the skin-to-skin contact is made between the skin and the skin cells. (6) (2) (2) 200407154 In an environment with the same mass and liquid, electrolyte balance and osmotic pressure balance were applied to discover water-based skin and hair cosmetics that can promote the normalization of even the cell surface and obstacle cells (Patent No. 1 597430). Therefore, the water-based skin and hair cosmetics can achieve the treatment of brown spots and red faces by stimulating subcutaneous cells to divide and treat, and the scalp and body odor by osmotic pressure to stimulate hair mother cells to promote hair and deodorization. The effect. That is, this water-based skin and hair cosmetic product has a therapeutic effect of 83% for hair removal, a therapeutic rate of 95% for pigmentation, and a therapeutic effect of 53% for red face. However, these effects mainly have no significant effect on the skin or hair. The inventor thought that the activation of skin cells and the like can activate mucosal cells without side effects, so for oral cavity inflammation caused by oral mucosal diseases, Or diseases such as hay fever caused by nasal mucosal disorders may also be effective for investigation. Therefore, the inventor has invented an external agent for promoting cell activity, which has no concerns about side effects even when used as an external agent for the oral cavity or nasal mucosa. For example, it can be applied to a wide range of cells such as stomatitis or hay fever. Various diseases (Patent No. 268 1 527). This external activity-promoting agent is a polysaccharide such as dextrin, or glucose, xylose, and lentinan. The agent for promoting cell activity can obtain excellent results for treating stomatitis with a treatment rate of 100% and for hay fever as a treatment rate of 100%. SUMMARY OF THE INVENTION However, the treatment rate for the flower (3) (3) 200 407 154 powdery disease as shown by the aforementioned external agent for promoting cell activity was shown when only 40 people were targeted at that time, and it was followed by hay fever The number of patients has increased rapidly, and the treatment rate of hay fever has a tendency to gradually decrease. That is, it is known that in the previous efficacy test (Heisei 2), those who showed 100% efficiency against hay fever, and after decades of present, the efficiency is inversely proportional to the explosive increase in incidence and rapidly decline. Although the cause of hay fever is not clear, it is presumed to be caused by personal factors that have certain effects on the cells of the oral cavity or nasal mucosa. Therefore, it can be speculated that in order to improve the immunity or healing ability of the oral cavity or nasal mucosa, it is necessary to maintain the healthy state of the cells and tissues, to prevent the adverse effects caused by various factors, to suppress the rapidly increasing incidence of hay fever, and to have a therapeutic effect. The present invention provides a modified external preparation for promoting cell activity, which can improve the immunity or healing ability of the oral cavity or nasal mucosa, and has no concerns about side effects. It can be applied to other than hay fever or endostomatitis Skin or scalp and other diseases at a wide range of cell levels. The first method of the present invention to achieve the above-mentioned object is to dissolve a polysaccharide in an aqueous solution to promote cell activity, and to add xyloglucan and 1-50% Kumbu polysaccharide, and 1-50% polysaccharide K (krestin). The second method is that the aqueous solution in which the polysaccharide is dissolved contains, as a whole, 1 to 50% of pectin, 1 to 30% of dextrin, 1 to 30% of glucose, and 1 to 40% of Amylopectin, 1 ~ 30% of lentinan, 1 ~ 50% of cyclodextrin and 1 ~ 50% of trehalose. The third method is that in an aqueous solution in which the polysaccharide is dissolved, a weight ratio of 0.1 to 1 sodium chloride, 0.1 to 1% calcium chloride, and -8-(4) is added to the whole. (4) 200,407,154 0.1 to 1% potassium chloride is the method to solve the problem. The symptoms of inflammation, pigmentation, hair loss and other symptoms on human skin are related to various factors such as ultraviolet rays and chemicals, which are limited to cell-level changes, and the salt is one of the small organs in the cell. Membrane or cell membrane disorders. That is, mitochondrial membrane disorders cause intracellular respiratory obstruction, which in turn reduces the production of ATP (adenosine triphosphate), a source of cellular motility. As a result of the lack of ATP, the energy transport function of the cell membrane is reduced, which reduces the material transport capacity between the cell and the interstitial fluid. As a result, the lack of nutrients such as glucose in the cells causes poor blood circulation caused by the decrease in ATP acidity. There are many reasons for the above-mentioned changes at the cell level. Especially for cells such as the oral cavity and nasal mucosa, the interstitial fluid is increased by osmotic pressure to activate cells at the disease site. In addition, it was learned that the addition of xyloglucan, kumbu polysaccharide, and polysaccharide K can improve the immunity or healing power of cellular tissues such as the oral cavity or nasal mucosa. Embodiments The present invention is basically formulated as an external agent for promoting cell activity by dissolving polysaccharides in an aqueous solution, and the whole is added in a weight ratio of 1 to 50% xyloglucan, 1 to 50% kumbu polysaccharide, and 1 ~ 50% of polysaccharide K (krestin) ° Xyloglucan is a sugar chain that is commonly found in the cell wall (primary wall) of elongating and hypertrophic plant cells. The specificity of plant species is due to the presence of xylose residues by galactose or fucose-galactose linkages. Although the galactose residue -9-(5) (5) 200407154 and the fucose residue can be bonded to lectin, respectively, the function of these branched sugar chains is unknown. The growth of plant cells is caused by the water absorption from the osmotic pressure of the cells, and the water absorption is caused by the reduction of the wall pressure caused by the relaxation of the cell wall. Although the relaxation of the cell wall is unknown, the elongation of the cell often causes the decomposition and solubilization of xyloglucan, and has attracted attention as one of the polysaccharides that manage the physiological activity of the cell. Kumbu polysaccharide is classified as one of the carbohydrates / 5/5 dextran Kumbu polysaccharide, which contains seaweeds such as chanterelle-based mushrooms or kumbu, which has the effect of improving immunity. It is known that it is difficult to absorb alone, and it must be taken together with protein. Polysaccharide K (kfestin) is an immunotherapeutic agent used to enhance the expression of the HLA class I antigen of human cancer cells, and is extracted from Mycelia kawachii. The polysaccharide K has been confirmed to have an immunotherapeutic effect on tumor diseases such as gastric cancer, colorectal and rectal cancer, and small cell lung cancer. The inventors studied ingredients suitable for external use from most polysaccharides. As a result, they combined these xyloglucan, kumbu polysaccharide, and polysaccharide K to improve the immunity of cellular tissues such as oral or nasal mucosa, or Healing topical. These polysaccharides are dissolved in an aqueous solution, and contain a weight ratio of 1 to 50% of pectin, 1 to 30% of dextrin, 1 to 30% of glucose, 1 to 30% of lentinan, 1 ~ 50% of trehalose. Cellulose and the like, which are structural components of plant cell walls, can be used for plant cell-related functions when combined with other components. The component having a colloid effect can be suitably used as an additive for the external preparation of the present invention. -10- (6) 200407154 In addition, sodium chloride, calcium chloride, and potassium chloride are added to the aqueous solution in which the polysaccharide is dissolved. 1〜1% ， Similarly for each calcium chloride with the effectiveness of the balance of the amount of sodium chloride on the skin permeability balance, the balance of electrolytes, that is, to activate skin cells for the whole 1 ~ 1% of potassium chloride is also dissolved in the aqueous phase component. [Example] Next, the effect of Formula 1 is shown in Table 1-Formula 1-Dextrin 18 Glucose 10 Cyclodextrin 2 Trehalose 3 Amylopectin 7 Lentinan 7 Polysaccharides Kumbu 2 Polysaccharide K 1 Pectin 3 Wood Dextran 1 Sodium oxide 0.9 Calcium chloride 0.3 Potassium chloride 0.3 Pure water 44.5 Weight ratio (%) 100
-11 - (7) 200407154 所謂水相成分（純水）係僅以純水製造之無油狀態， 完全無含製造化粧品等一般之外用劑時所使用的水溶性石 油系之界面活性劑等。因此，混合這些成分的水相成分 時，欲完全溶解各成分而於50〜10(TC下實施。 表1 疾病名 對象人數 有效性（點） 有效率（％) 男性型脫毛症 60 118 98 身心性脫毛症 50 60 60 痤瘡 30 58 97 紅臉 60 66 55 足癖 50 95 95 脂漏性皮膚炎 100 197 99 異位性皮膚炎 100 98 4 9 口內炎 50 100 100 花粉症 100 196 98-11-(7) 200407154 The so-called water phase component (pure water) is an oil-free state made of pure water only, and completely free of water-soluble oil-based surfactants used in the manufacture of general external agents such as cosmetics. Therefore, when mixing the water-phase components of these components, the components should be dissolved at 50 to 10 (TC) in order to completely dissolve the components. Table 1 Number of patients with disease names Effectiveness (points) Effectiveness (%) Male hair loss 60 118 98 Alopecia 50 60 60 acne 30 58 97 red face 60 66 55 foot fetish 50 95 95 alopecia dermatitis 100 197 99 atopic dermatitis 100 98 4 9 stomatitis 50 100 100 hay fever 100 196 98
表1表示處方例1的藥理試驗所得結果。此時的有效 性，經使用本發明外用劑，無變化爲0點，有痊癒變化爲 1點，確認有效果爲2點，而合計各個人之總點，並以下 述式算出有效性。且’本次試驗爲特別要確認花粉症之痊 癒效果，以1 00個患者作爲對象算出有效率。 【數1】 有效率= 總點 對象人數X2_ xl 00 -12- (8) 200407154 其結果，對於1 00人的花粉症作爲對象時亦可得到 98%有效率。對於前次（平成2年）的試驗，花粉症下顯 示100%的有效率者，其後經過數十年的今天，卻與發病 率的爆發性增加成反比，其有效率急速下降。故本發明可 維持98%的有效率爲特別値得一提之效果。又’ 6〇〇病例 中，未確認出無副作用的例子，且對男性脫毛症或痤瘡、 足癬、脂漏性皮膚炎等難治療之疾病極爲有用。Table 1 shows the results obtained from the pharmacological test of Formulation 1. The effectiveness at this time was 0 points when no external agent of the present invention was used, 1 point when there was a healing change, 2 points when the effect was confirmed, and the total points of each person were totaled, and the effectiveness was calculated by the following formula. In addition, in this test, in order to confirm the healing effect of hay fever, the effective rate was calculated for 100 patients. [Number 1] Effectiveness = total points Number of subjects X2_ xl 00 -12- (8) 200407154 As a result, for 100 people with hay fever, 98% efficiency can be obtained. For the previous test (Heisei 2 years), those who showed 100% efficiency under hay fever, but after decades of today, they are inversely proportional to the explosive increase in the incidence, and their effectiveness has dropped rapidly. Therefore, the effective rate of the present invention which can maintain 98% is particularly noticeable. In the '600' case, no side effect was not confirmed, and it was extremely useful for men's alopecia, acne, athlete's foot, and adipose dermatitis, which are difficult to treat.
且，由處方例2的混合比所調出之本發明外用劑。 -處方例2 -In addition, the external preparation of the present invention is prepared from the mixing ratio of Formula 2. -Prescription example 2-
糊精 4 葡萄糖 3 xm Jffn 中幸 壞糊精 2 海藻糖 3 支鏈澱粉 3 香菇多醣 3 昆布多醣 2 多醣體K 1 果膠 3 木葡聚醣 50 氧化鈉 0.4 氯化鈣 0.3 氯化鉀 0,3 純水 25 計 100 重量比（％ ) -13- 200407154 Ο) 其結果，得知木葡聚醣的濃度提高至處方例2以上 時，會有溶解後分離之現象，成爲不當的處方。又，木葡 聚醣之外，昆布多醣、多醣體K之任一必須於至少1 %以 上濃度時顯示有效性，又各濃度超過5 0 %時無法成爲處 方。 【發明的效果】 本發明係爲，對全體而言添加重量比爲，1〜5 0 %的 木葡聚醣、1〜5〇%的昆布多醣、與1〜5〇%的多醣體K (kre st in )的各成分水相成分中，可提高口腔或鼻黏膜等 細胞組織之免疫力或痊癒力，得到對花粉症等個人因素之 疾病亦有治療效果。 又，提高細胞組織的免疫力或痊癒力之同時，可製造 出與皮膚細胞間質液相同之環境，而預防粒線體的膜障礙 所引起的細胞內呼吸障礙、或細胞活動源之ATP (腺苷三 磷酸）生產降低，亦可保持電解質平衡、滲透壓平衡，並 促進皮膚細胞或黏膜細胞表層的障礙細胞之正常化，且對 男性脫毛症或痤瘡、足癬、脂漏性皮膚炎等難治療之疾病 極爲有用。本發明的意義極大對人類的貢獻亦大。 -14-Dextrin 4 Glucose 3 xm Jffn Medium Fortunate Dextrin 2 Trehalose 3 Amylopectin 3 Lentinan 3 Kumbu Polysaccharide 2 Polysaccharide K 1 Pectin 3 Xyloglucan 50 Sodium Oxide 0.4 Calcium Chloride 0.3 Potassium Chloride 0, 3 Pure water 25 based on 100 weight ratio (%) -13- 200407154 〇) As a result, it was found that when the concentration of xyloglucan was increased to above Formulation 2 or above, there was a phenomenon of separation after dissolution, which became an inappropriate prescription. In addition, besides xyloglucan, any one of kumbu polysaccharide and polysaccharide K must show effectiveness at a concentration of at least 1%, and cannot be treated when each concentration exceeds 50%. [Effects of the Invention] The present invention is to add xyloglucan of 1 to 50% by weight, konbu polysaccharide of 1 to 50%, and polysaccharide K of 1 to 50% ( kre st in) of the water phase components can improve the immunity or healing power of cellular tissues such as the oral cavity or nasal mucosa, and also have therapeutic effects on diseases such as hay fever and other personal factors. In addition, while improving the immunity or healing power of cellular tissues, it can create the same environment as the interstitial fluid of skin cells, and prevent intracellular respiratory disorders caused by mitochondrial membrane disorders or ATP (source of cellular activity) ( Reduced adenosine triphosphate) production, it can also maintain electrolyte balance, osmotic pressure balance, and promote the normalization of skin cells or mucosal cell surface disorder cells, and for male hair removal or acne, athlete's foot, alopecia dermatitis, etc. Intractable diseases are extremely useful. The significance of the present invention is great for human contribution. -14-