TWI788648B - Chinese medicine composition for skin dressing as well as skin dressing and manufacturing method of the same - Google Patents
Chinese medicine composition for skin dressing as well as skin dressing and manufacturing method of the same Download PDFInfo
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- TWI788648B TWI788648B TW109110840A TW109110840A TWI788648B TW I788648 B TWI788648 B TW I788648B TW 109110840 A TW109110840 A TW 109110840A TW 109110840 A TW109110840 A TW 109110840A TW I788648 B TWI788648 B TW I788648B
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Abstract
一種皮膚敷藥的中藥成分、皮膚敷藥及其製造方法,其中該皮膚敷藥的中藥成分包含:黃連、黃芩、黃柏、梔子、桑白皮、苦參根、連翹、龍膽草、石膏以及土茯芩。藉此,可以有效改善病患在使用癌症標靶藥物所引起之皮膚病副作用,進而使病患能順利接受癌症正規治療,並在治療期間仍能維持良好的生活品質。A traditional Chinese medicine composition of a skin dressing, a skin dressing and a manufacturing method thereof, wherein the Chinese medicine composition of the skin dressing includes: Coptis chinensis, Scutellaria baicalensis, Cortex Phellodendron, Gardenia, Cortex Mori, Sophora flavescens, Forsythia, Gentiana, and gypsum And Smilax baicalensis. In this way, the side effects of skin diseases caused by the use of cancer targeted drugs can be effectively improved, so that patients can successfully receive regular cancer treatment and maintain a good quality of life during treatment.
Description
本發明係關於一種皮膚敷藥的中藥成分、皮膚敷藥及其製造方法。 The invention relates to a traditional Chinese medicine composition of a skin dressing, a skin dressing and a manufacturing method thereof.
癌症標靶藥物,如表皮生長因子接受器阻斷劑(Epidermal Growth Factor Receptor Inhibitor,EGFRIs)可區分為兩大藥物:一種為單株抗體大分子藥物,如Cetuximab(Erbitux,爾必得舒),另一種為小分子藥物EGFR抑制劑,如Gefitinib(Iressa,艾瑞沙)、Erlotinib(Tarceva,得舒緩)、Lapatinib(Tykerb,泰嘉錠)等,這類標靶藥物,最常見的皮膚反應是丘疹膿皰樣痤瘡(papulopustular acneiform eruption)。而酪胺酸脢路徑抑制劑(Tyrosine kinase inhibitors),例如:Sunitinib(Sutent,紓癌特)、Sorafenib(Nexavar,蕾莎瓦),這些容易產生「手足皮膚反應」(Hand foot skin reaction,HFSR),在腳底、腳指、腳外側等受壓處會出現紅斑,角質化厚繭(雞眼),甚至水泡。其他皮膚反應包括掉髮、皮膚乾燥、皮膚搔癢、脂溢性皮炎樣皮疹等。目前西醫的治療方式多輔以痤瘡口服或外用藥物治療,或再合併外用類固醇藥膏來治療。當嚴重發炎時,甚至必須停止標靶藥物。 Cancer target drugs, such as epidermal growth factor receptor inhibitors (Epidermal Growth Factor Receptor Inhibitor, EGFRIs) can be divided into two major drugs: one is monoclonal antibody macromolecular drugs, such as Cetuximab (Erbitux, Erbidux), and the other One is a small-molecule drug EGFR inhibitor, such as Gefitinib (Iressa, Iressa), Erlotinib (Tarceva, Desoo), Lapatinib (Tykerb, Taijia Tablet), etc. The most common skin reaction of this type of target drug is papules Pustular acne (papulopustular acneiform eruption). And tyrosine kinase inhibitors (Tyrosine kinase inhibitors), such as: Sunitinib (Sutent, Shuai special), Sorafenib (Nexavar, Leisava), these are prone to "hand foot skin reaction" (Hand foot skin reaction, HFSR) , Erythema, keratinized thick calluses (corns), and even blisters will appear on the soles of the feet, toes, and outside of the feet under pressure. Other skin reactions include hair loss, dry skin, itchy skin, and seborrheic dermatitis-like rash. At present, the treatment methods of Western medicine are mostly supplemented by oral or external medication for acne, or combined with external steroid ointment for treatment. When inflammation is severe, even targeted drugs must be stopped.
而在中醫方面,中醫的觀點認為這些皮膚病副作用是藥毒內侵引起的藥毒疹,多以具有清熱解毒、清熱涼血、清熱瀉火等作用的中藥作為治療。現有以中藥改善皮膚的方式例如有中華民國專利公告號I626054提供的一種中草藥抗痘貼片,其包含:一載藥體,其具有一第一層體及一第二層體,第一層體具有多孔性結構,第二層體為緊密結構且黏貼性較強於第一層體,而第二層體與第一層體之其中一表面相互結合,其中,載藥體係包含一抗痘複方,其係選自於一黃柏萃取液濃度為1至2mg/ml、一積雪草萃取液濃度為1至3mg/ml、一虎杖萃取液濃度為1至2mg/ml、一石榴皮萃取液濃度為0.1至1mg/ml及一洋甘菊萃取液濃度為0.1至1mg/ml所組成之群組,藉此,抗痘複方為天然成分,且能有效抑制細菌生長,以達到幫助傷口修復之效果。 In terms of traditional Chinese medicine, the point of view of traditional Chinese medicine is that the side effects of these skin diseases are drug eruptions caused by the internal invasion of drug poisons, and most of them are treated with traditional Chinese medicines that have the functions of clearing heat and detoxifying, clearing heat and cooling blood, clearing heat and purging fire. Existing ways to improve skin with traditional Chinese medicine, such as a Chinese herbal medicine anti-acne patch provided by the Republic of China Patent Publication No. I626054, include: a drug carrier, which has a first layer and a second layer, the first layer It has a porous structure, the second layer has a compact structure and stronger adhesion than the first layer, and the second layer is combined with one of the surfaces of the first layer, wherein the drug-loading system includes an anti-acne compound , which is selected from a Phellodendron Phellodendri extract with a concentration of 1 to 2 mg/ml, a Centella asiatica extract with a concentration of 1 to 3 mg/ml, a Polygonum cuspidatum extract with a concentration of 1 to 2 mg/ml, and a pomegranate peel extract with a concentration of The group consisting of 0.1 to 1mg/ml and a chamomile extract concentration of 0.1 to 1mg/ml, so that the anti-acne compound is a natural ingredient, and can effectively inhibit the growth of bacteria to achieve the effect of helping wound repair.
然而,前述專利案使用的成分僅有中草藥,在改善皮膚病副作用的效果上可能較為侷限而耗時。 However, the ingredients used in the aforementioned patents are only Chinese herbal medicines, which may be relatively limited and time-consuming in improving the side effects of skin diseases.
爰此,本發明人提出一種皮膚敷藥的中藥成分,適用於改善癌症標靶藥物引起的皮膚病副作用,該皮膚敷藥的中藥成分包含:黃連656.25至1031.25之間的重量份;黃芩375至750之間的重量份;黃柏375至750之間的重量份;梔子656.25至1031.25之間的重量份;桑白皮187.5至562.5之間的重量份;苦參根375至750之間的重量份;連翹187.5至562.5之間的重量份;龍膽草112.5至300之間的重量份;石膏862.5至1125之間的重量份;以及土茯芩375至750之間的重量份。 Therefore, the inventor proposes a traditional Chinese medicine component of a skin dressing, which is suitable for improving the side effects of skin diseases caused by cancer target drugs. 750 parts by weight; Phellodendron 375 to 750 parts by weight; Gardenia 656.25 to 1031.25 parts by weight; Morus alba 187.5 to 562.5 parts by weight; Sophora flavescens root 375 to 750 parts by weight parts by weight; parts by weight of Forsythia 187.5 to 562.5; parts by weight of Gentiana 112.5 to 300; parts by weight of gypsum 862.5 to 1125; and parts by weight of Smilax 375 to 750.
本發明也是一種皮膚敷藥,適用於改善癌症標靶藥物引起的皮膚病副作用,該皮膚敷藥除了包含上述皮膚敷藥的中藥成分,進一步包含:20.276 至30.414之間的重量份的純水、1.6至2.4之間的重量份的甘油、1.6至2.4之間的重量份的1,3-丁二醇(Butylene Glycol)、0.8至1.2之間的重量份的海藻酸鈉、1.6至2.4之間的重量份的乙醯胺基乙氧基乙醇、0.16至0.24之間的重量份的對羥基苯甲酸甲酯、0.48至0.72之間的重量份的小核菌膠、2.4至3.6之間的重量份的聚甘油6硬脂酸酯、1.6至2.4之間的重量份的自行乳化之甘油硬脂酸、0.8至1.2之間的重量份的十六烷基磷酸鉀、1.6至2.4之間的重量份的二十二烷醇、1.6至2.4之間的重量份的硬脂醇、0.8至1.2之間的重量份的硬脂酸、4.8至7.2之間的重量份的異硬脂酸異丙酯、2.4至3.6之間的重量份的異硬脂酸、0.8至1.2之間的重量份的辛基十二烷醇、1.6至2.4之間的重量份的辛酸/癸酸三酸甘油酯、2.4至3.6之間的重量份的荷荷巴油、2.4至3.6之間的重量份的夏威夷豆油、0.4至0.6之間的重量份的維生素E、0.8至1.2之間的重量份的異十二烷、0.8至1.2之間的重量份的二甲基矽氧烷、0.2至0.3之間的重量份的苯氧乙醇、0.004至0.006之間的重量份的吡羅克酮乙醇銨鹽及0.08至0.12之間的重量份的對羥基苯甲酸丙烯酯。 The present invention is also a skin dressing, which is suitable for improving the side effects of skin diseases caused by cancer target drugs. In addition to the traditional Chinese medicine ingredients of the skin dressing, the skin dressing further includes: 20.276 30.414 parts by weight of pure water, 1.6 to 2.4 parts by weight of glycerin, 1.6 to 2.4 parts by weight of 1,3-butanediol (Butylene Glycol), 0.8 to 1.2 parts by weight Parts of sodium alginate, parts by weight of acetamidoethoxyethanol between 1.6 and 2.4 parts by weight, parts by weight of methyl p-hydroxybenzoate between 0.16 and 0.24 parts by weight, small parts by weight between 0.48 and 0.72 parts Sclerotin, 2.4 to 3.6 parts by weight of polyglycerol 6 stearate, 1.6 to 2.4 parts by weight of self-emulsifying glyceryl stearic acid, 0.8 to 1.2 parts by weight of hexadecane Potassium phosphate, 1.6 to 2.4 parts by weight of behenyl alcohol, 1.6 to 2.4 parts by weight of stearyl alcohol, 0.8 to 1.2 parts by weight of stearic acid, 4.8 to 7.2 parts by weight Parts by weight of isopropyl isostearate, parts by weight of isostearic acid between 2.4 and 3.6 parts by weight, parts by weight of octyldodecanol between 0.8 and 1.2 parts by weight, parts by weight between 1.6 and 2.4 caprylic/capric triglyceride, jojoba oil between 2.4 and 3.6 parts by weight, macadamia oil between 2.4 and 3.6 parts by weight, vitamin E between 0.4 and 0.6 parts by weight, 0.8 to 1.2 parts by weight of isododecane, 0.8 to 1.2 parts by weight of dimethylsiloxane, 0.2 to 0.3 parts by weight of phenoxyethanol, 0.004 to 0.006 parts by weight of Piroctone ethanolammonium salt and 0.08 to 0.12 parts by weight of allyl p-hydroxybenzoate.
本發明也是一種用於改善癌症標靶藥物引起的皮膚病副作用的皮膚敷藥的中藥成分之製造方法,包含:將656.25至1031.25之間的重量份的黃連、375至750之間的重量份的黃芩、375至750之間的重量份的黃柏、656.25至1031.25之間的重量份的梔子、187.5至562.5之間的重量份的桑白皮、375至750之間的重量份的苦參根、187.5至562.5之間的重量份的連翹、112.5至300之間的重量份的龍膽草、862.5至1125之間的重量份的石膏、375至750之間的重量份的土茯芩,以及18040至27060之間的重量份的水混合成一混合液;以及將該混合液煮120至180分鐘後,濃縮至濃度介於20%至40%之間而成為一皮膚敷藥。 The present invention is also a manufacturing method of traditional Chinese medicine components of skin dressings for improving side effects of skin diseases caused by cancer target drugs. Scutellaria baicalensis, 375 to 750 parts by weight of Cortex Phellodendri, 656.25 to 1031.25 parts by weight of Gardenia, 187.5 to 562.5 parts by weight of Cortex Morus alba, 375 to 750 parts by weight of Sophora flavescens root , 187.5 to 562.5 parts by weight of forsythia, 112.5 to 300 parts by weight of gentian, 862.5 to 1125 parts by weight of gypsum, 375 to 750 parts by weight of Smilax, and 18040 to 27060 parts by weight of water are mixed to form a mixed solution; and after boiling the mixed solution for 120 to 180 minutes, it is concentrated to a concentration between 20% and 40% to form a skin dressing.
本發明也是一種用於改善癌症標靶藥物引起的皮膚病副作用的皮膚敷藥之製造方法,包含上述皮膚敷藥的中藥成分之製造方法,進一步包含:將0.8至1.2之間的重量份的海藻酸鈉和0.48至0.72之間的重量份的小核菌膠以水作為溶劑,在攝氏40度至50度下溶解;再加入20.276至30.414之間的重量份的純水、1.6至2.4之間的重量份的甘油、1.6至2.4之間的重量份的1,3至丁二醇、1.6至2.4之間的重量份的乙醯胺基乙氧基乙醇、0.16至0.24之間的重量份的對羥基苯甲酸甲酯及2.4至3.6之間的重量份的聚甘油6硬脂酸酯,加熱至攝氏70至80度後成為一第一混合液;將1.6至2.4之間的重量份的自行乳化之甘油硬脂酸、0.8至1.2之間的重量份的十六烷基磷酸鉀、1.6至2.4之間的重量份的二十二烷醇、1.6至2.4之間的重量份的硬脂醇、0.8至1.2之間的重量份的硬脂酸、4.8至7.2之間的重量份的異硬脂酸異丙酯、2.4至3.6之間的重量份的異硬脂酸、0.8至1.2之間的重量份的辛基十二烷醇、1.6至2.4之間的重量份的辛酸/癸酸三酸甘油酯、2.4至3.6之間的重量份的荷荷巴油、2.4至3.6之間的重量份的夏威夷豆油及0.4至0.6之間的重量份的維生素E混合加熱至攝氏75至85度後成為一第二混合液;將該第二混合液加入該第一混合液,乳化後成為一第三混合液;該第三混合液降溫至攝氏55至65度時,加入0.8至1.2之間的重量份的異十二烷、0.8至1.2之間的重量份的二甲基矽氧烷、0.2至0.3之間的重量份的苯氧乙醇、0.004至0.006之間的重量份的吡羅克酮乙醇銨鹽及0.08至0.12之間的重量份的對羥基苯甲酸丙烯酯混合;以及該第三混合液降溫至攝氏25至30度時,加入28至42之間的重量份的濃縮後的該混合液,混合成為該皮膚敷藥。 The present invention is also a method for manufacturing skin dressings for improving the side effects of skin diseases caused by cancer target drugs, including the manufacturing method of the traditional Chinese medicine components of the above skin dressings, further comprising: seaweed in an amount of 0.8 to 1.2 parts by weight Sodium acid sodium and 0.48 to 0.72 parts by weight of sclerotin gum are dissolved with water as a solvent at 40 to 50 degrees Celsius; then add 20.276 to 30.414 parts by weight of pure water, 1.6 to 2.4 parts Parts by weight of glycerol, parts by weight of 1,3 to butanediol between 1.6 and 2.4 parts by weight, parts by weight of acetamidoethoxyethanol between 1.6 and 2.4 parts by weight, parts by weight between 0.16 and 0.24 parts by weight of The polyglycerol 6 stearate of methyl p-hydroxybenzoate and 2.4 to 3.6 parts by weight is heated to 70 to 80 degrees Celsius to form a first mixed solution; the parts by weight between 1.6 and 2.4 Emulsified glyceryl stearic acid, potassium cetyl phosphate between 0.8 and 1.2 parts by weight, behenyl alcohol between 1.6 and 2.4 parts by weight, stearyl alcohol between 1.6 and 2.4 parts by weight , 0.8 to 1.2 parts by weight of stearic acid, 4.8 to 7.2 parts by weight of isopropyl isostearate, 2.4 to 3.6 parts by weight of isostearic acid, 0.8 to 1.2 parts by weight Parts by weight of octyldodecanol, between 1.6 and 2.4 parts by weight of caprylic/capric triglycerides, between 2.4 and 3.6 parts by weight of jojoba oil, between 2.4 and 3.6 parts by weight Parts of macadamia soybean oil and 0.4 to 0.6 parts by weight of vitamin E are mixed and heated to 75 to 85 degrees Celsius to form a second mixed solution; the second mixed solution is added to the first mixed solution, and emulsified to form a second mixed solution Three mixed liquids; when the third mixed liquid is cooled to 55 to 65 degrees Celsius, add 0.8 to 1.2 parts by weight of isododecane, 0.8 to 1.2 parts by weight of dimethylsiloxane, 0.2 0.3 parts by weight of phenoxyethanol, 0.004 to 0.006 parts by weight of piroctone ethanolammonium salt and 0.08 to 0.12 parts by weight of propylene p-hydroxybenzoate; and the third When the temperature of the mixed solution is lowered to 25 to 30 degrees Celsius, 28 to 42 parts by weight of the concentrated mixed solution is added and mixed to form the skin dressing.
本發明也是一種以前述皮膚敷藥之製造方法製造的皮膚敷藥。 The present invention is also a skin dressing manufactured by the aforementioned manufacturing method of the skin dressing.
根據上述技術特徵可達成以下功效: 將以上化合物結合特定中藥成分,並以藥膏濕敷、塗抹方式,適用於標靶藥物,如表皮生長因子接受器阻斷器(Epidermal Growth Factor Receptor Inhibitor,EGFRIs)和酪氨酸激酶抑制劑(Tyrosine kinase inhibitors,TKI)所誘發的皮膚病副作用的治療包含類似痤瘡樣的紅疹(likeacne form of skin rash)或丘疹膿皰皮疹(papulopustular eruption)、皮膚瘙癢(pruritus)、皮膚乾燥(xerosis)、甲溝炎(paronychia)手足皮膚反應(hand foot skin reaction,HFSR)和化療藥物所引起的皮膚丘疹、膿皰等症狀。 According to the above-mentioned technical features, the following effects can be achieved: Combining the above compounds with specific traditional Chinese medicine ingredients, and wet dressing and smearing with ointment, it is suitable for targeted drugs, such as Epidermal Growth Factor Receptor Inhibitors (EGFRIs) and Tyrosine Kinase Inhibitors (Tyrosine Kinase Inhibitors) Treatment of dermatological side effects induced by skin inhibitors (TKI) includes acne-like erythema (like acne form of skin rash) or papulopustular eruption (papulopustular eruption), skin itching (pruritus), skin dryness (xerosis), nail Paronychia, hand foot skin reaction (HFSR) and skin papules, pustules and other symptoms caused by chemotherapy drugs.
[第一圖]係本發明實施例之流程示意圖。 [The first figure] is a schematic flow chart of the embodiment of the present invention.
[第二A圖]係未使用本發明實施例皮膚敷藥之照片一,拍攝日期:2019年11月27日。 [Second Figure A] is the first photo of the skin application without using the embodiment of the present invention, and the shooting date: November 27, 2019.
[第二B圖]係使用本發明實施例皮膚敷藥之照片一,拍攝日期:2019年12月13日。 [Picture 2 B] is photo 1 of using the skin dressing according to the embodiment of the present invention, and the shooting date: December 13, 2019.
[第三A圖]係未使用本發明實施例皮膚敷藥之照片二,拍攝日期:2019年8月19日。 [Third Picture A] is the second picture without using the skin dressing according to the embodiment of the present invention, taken on August 19, 2019.
[第三B圖]係使用本發明實施例皮膚敷藥之照片二,拍攝日期:2019年10月14日。 [Third Picture B] is the second picture of using the skin dressing according to the embodiment of the present invention, and the shooting date: October 14, 2019.
[第四A圖]係未使用本發明實施例皮膚敷藥之照片三,拍攝日期:2019年6月10日。 [Picture 4 A] is photo 3 without using the skin dressing according to the embodiment of the present invention, date of shooting: June 10, 2019.
[第四B圖]係使用本發明實施例皮膚敷藥之照片三,拍攝日期:2019年8月5日。 [Picture 4 B] is photo 3 using the skin dressing according to the embodiment of the present invention, date of shooting: August 5, 2019.
[第五A圖]係未使用本發明實施例皮膚敷藥之照片四,拍攝日期:2019年8月7日。 [Fifth Figure A] is the fourth photo without using the skin dressing according to the embodiment of the present invention, and the shooting date: August 7, 2019.
[第五B圖]係使用本發明實施例皮膚敷藥之照片四,拍攝日期:2019年12月18日。 [Fifth Figure B] is the photo 4 of using the skin dressing according to the embodiment of the present invention, and the shooting date: December 18, 2019.
[第六A圖]係未使用本發明實施例皮膚敷藥之照片五,拍攝日期:2019年6月19日。 [Picture 6 A] is photo 5 without using the skin dressing of the embodiment of the present invention, and the shooting date: June 19, 2019.
[第六B圖]係使用本發明實施例皮膚敷藥之照片五,拍攝日期:2019年8月21日。 [Picture 6 B] is photo 5 using the skin dressing according to the embodiment of the present invention, date of shooting: August 21, 2019.
綜合上述技術特徵,本發明皮膚敷藥的中藥成分、皮膚敷藥及其製造方法的主要功效將可於下述實施例清楚呈現。 Based on the above-mentioned technical features, the main functions of the traditional Chinese medicine ingredients, the skin dressing and its manufacturing method of the skin dressing of the present invention will be clearly presented in the following examples.
請參閱第一圖,係揭示該皮膚敷藥的製造方法。該皮膚敷藥適用於改善癌症標靶藥物引起的皮膚病副作用。 Please refer to the first figure, which discloses the manufacturing method of the skin dressing. The skin dressing is suitable for improving skin disease side effects caused by cancer target drugs.
先將介於656.25公克至1031.25公克之間的黃連、介於375公克至750公克之間的黃芩、介於375公克至750公克之間的黃柏、介於656.25公克至1031.25公克之間的梔子、介於187.5公克至562.5公克之間的桑白皮、介於375公克至750公克之間的苦參根、介於187.5公克至562.5公克之間的連翹、介於112.5公克至300公克之間的龍膽草、介於862.5公克至1125公克之間已打碎成細粉的石膏、介於375公克至750公克之間的土茯芩,以及介於18040毫升至27060毫升之間的純水混合成一混合液,將該混合液煮150分鐘後至15000毫升,並濃縮至30%的濃度備用。 Coptidis between 656.25 grams and 1031.25 grams, skullcap between 375 grams and 750 grams, cork between 375 grams and 750 grams, gardenia between 656.25 grams and 1031.25 grams , between 187.5 grams and 562.5 grams of Morus alba, between 375 grams and 750 grams of Sophora flavescens root, between 187.5 grams and 562.5 grams of forsythia, between 112.5 grams and 300 grams gentian, between 862.5 grams and 1125 grams of gypsum that has been crushed into fine powder, between 375 grams and 750 grams of Smilax, and between 18040 milliliters and 27060 milliliters of purified water Mixed into a mixture, the mixture was boiled for 150 minutes to 15000 ml, and concentrated to a concentration of 30% for later use.
接著將介於0.8重量份至1.2重量份之間的海藻酸鈉(Sodium Alginate)和介於0.48重量份至0.72重量份之間的小核菌膠(Sclerotium Gum)以水做為溶劑,在攝氏40度至50度下溶解;加入介於20.276重量份至30.414重量份之間的純水、介於1.6重量份至2.4重量份之間的甘油(Glycerin)、介於1.6重量份至2.4重量份之間的1,3-丁二醇(Butylene Glycol)、介於1.6重量份至2.4重量份之間的乙醯胺基乙氧基乙醇(Acetamidoethoxyethanol)、介於0.16重量份至0.24重量份之間的對羥基苯甲酸甲酯(Methylparaben)及介於2.4重量份至3.6重量份之間的聚甘油6硬脂酸酯(Polyglyceryl-6 Stearate),加熱至攝氏75度溶解後成為一第一混合液備用。 Then, 0.8 to 1.2 parts by weight of sodium alginate (Sodium Alginate) and 0.48 to 0.72 parts by weight of sclerotium gum (Sclerotium Gum) were used as solvent in water at Dissolve at 40 to 50 degrees; add between 20.276 parts by weight and 30.414 parts by weight of pure water, between 1.6 parts by weight and 2.4 parts by weight of glycerin (Glycerin), between 1.6 parts by weight and 2.4 parts by weight Between 1,3-butanediol (Butylene Glycol), between 1.6 parts by weight to 2.4 parts by weight of acetamidoethoxyethanol (Acetamidoethoxyethanol), between 0.16 parts by weight to 0.24 parts by weight Methylparaben (Methylparaben) and polyglyceryl-6 stearate (Polyglyceryl-6 Stearate) between 2.4 parts by weight and 3.6 parts by weight are heated to 75 degrees Celsius to dissolve and become a first mixed solution spare.
將介於1.6重量份至2.4重量份之間的自行乳化之甘油硬脂酸(Glyceryl Stearate SE)、介於0.8重量份至1.2重量份之間的十六烷基磷酸鉀(Potassium Cetyl Phosphate)、介於1.6重量份至2.4重量份之間的二十二烷醇(Behenyl Alcohol)、介於1.6重量份至2.4重量份之間的硬脂醇(Stearyl Alcohol)、介於0.8重量份至1.2重量份之間的硬脂酸(Stearic Acid)、介於4.8重量份至7.2重量份之間的異硬脂酸異丙酯(Isopropyl Isostearate)、介於2.4重量份至3.6重量份之間的異硬脂酸(IsostearicAcid)、介於0.8重量份至1.2重量份之間的辛基十二烷醇(Octyldodecanol)、介於1.6重量份至2.4重量份之間重量份的辛酸/癸酸三酸甘油酯(Caprylic/Capric Triglyceride)、介於2.4重量份至3.6重量份之間的荷荷巴油(Jojoba Oil)、介於2.4重量份至3.6重量份之間的夏威夷豆油(Macadamia Nut Oil)及介於0.4重量份至0.6重量份之間的維生素E(Vitamin E)混合加熱至攝氏80度溶解後成為一第二混合液備用。 Self-emulsifying glyceryl stearate (Glyceryl Stearate SE) between 1.6 parts by weight and 2.4 parts by weight, potassium cetyl phosphate (Potassium Cetyl Phosphate) between 0.8 parts by weight and 1.2 parts by weight, Between 1.6 parts by weight and 2.4 parts by weight of behenyl alcohol (Behenyl Alcohol), between 1.6 parts by weight and 2.4 parts by weight of stearyl alcohol (Stearyl Alcohol), between 0.8 parts by weight and 1.2 parts by weight Stearic Acid (Stearic Acid) between 4.8 to 7.2 parts by weight Isopropyl Isostearate (Isopropyl Isostearate) between 2.4 and 3.6 parts by weight Isostearic Acid, Octyldodecanol between 0.8 and 1.2 parts by weight, caprylic/capric triglyceride between 1.6 and 2.4 parts by weight (Caprylic/Capric Triglyceride), between 2.4 parts by weight and 3.6 parts by weight of jojoba oil (Jojoba Oil), between 2.4 parts by weight and 3.6 parts by weight of macadamia nut oil (Macadamia Nut Oil) and between 0.4 parts by weight to 0.6 parts by weight of vitamin E (Vitamin E) are mixed and heated to 80 degrees centigrade to dissolve and become a second mixed solution for later use.
將該第二混合液加入該第一混合液,乳化後成為一第三混合液。使該第三混合液降溫,當該第三混合液降溫至攝氏60度時,加入介於0.8重量份至1.2重量份之間的異十二烷(Isododecane)、介於0.8重量份至1.2重量份之間的二甲基矽氧烷(Dimethicone)、介於0.2重量份至0.3重量份之間的苯氧乙醇(Phenoxyethanol)、介於0.004重量份至0.006重量份之間的吡羅克酮乙醇銨鹽(Piroctone Olamine)及介於0.08重量份至0.12重量份之間的對羥基苯甲酸丙烯酯(Propylene Paraben)混合攪拌均勻。繼續使該第三混合液降溫,當該第三混合液降溫至攝氏28度時,加入介於28重量份至42重量份之間的濃縮後的該混合液,均勻混合而成為一皮膚敷藥。 The second mixed solution is added to the first mixed solution to form a third mixed solution after emulsification. The third mixed liquid is cooled, and when the third mixed liquid is cooled to 60 degrees Celsius, add between 0.8 to 1.2 parts by weight of isododecane (Isododecane), between 0.8 to 1.2 parts by weight Dimethicone (Dimethicone) between parts, Phenoxyethanol (Phenoxyethanol) between 0.2 parts by weight and 0.3 parts by weight, piroctone ethanol between 0.004 parts by weight and 0.006 parts by weight Ammonium salt (Piroctone Olamine) and 0.08 to 0.12 parts by weight of propylene paraben (Propylene Paraben) are mixed and stirred evenly. Continue to cool down the third mixed solution, when the third mixed solution is cooled to 28 degrees Celsius, add between 28 parts by weight and 42 parts by weight of the concentrated mixed solution, and mix evenly to form a skin dressing .
一、重金屬殘留量檢驗: 1. Inspection of heavy metal residues:
依據衛生福利部的規定,化粧品最終製品中含不純物重金屬鎘之殘留量不得超過5ppm、鉛不得超過10ppm、砷不得超過3ppm,而中藥材分項重金屬限量基準通則也限制鎘不得超過1ppm、鉛不得超過5ppm、砷不得超過3ppm。 According to the regulations of the Ministry of Health and Welfare, the residual amount of heavy metal cadmium, lead, and arsenic in final cosmetic products shall not exceed 5ppm, lead shall not exceed 10ppm, and arsenic shall not exceed 3ppm. More than 5ppm, arsenic must not exceed 3ppm.
為了確認是否符合前述規定,本發明人委託國立嘉義大學生命科學院檢驗分析及技術推廣服務中心食品檢驗組對該皮膚敷藥進行重金屬殘留量的檢驗,使用原子吸收光譜儀的檢驗結果為:鎘0.013ppm;鉛0.085ppm;砷未檢出,證明該皮膚敷藥確實符合且遠低於衛生福利部對化粧品及中藥材的重金屬限制量。 In order to confirm whether it complies with the aforementioned regulations, the inventor entrusted the food inspection team of the Inspection Analysis and Technology Extension Service Center of the National Chiayi University College of Life Sciences to inspect the heavy metal residues of the skin dressing, and the inspection result using an atomic absorption spectrometer was: cadmium 0.013ppm ; Lead 0.085ppm; Arsenic was not detected, which proves that the skin dressing really meets and is far below the Ministry of Health and Welfare's heavy metal limit for cosmetics and Chinese herbal medicines.
二、農藥殘留量檢驗: 2. Inspection of pesticide residues:
本發明人同樣委託國立嘉義大學生命科學院檢驗分析及技術推廣服務中心食品檢驗組對該皮膚敷藥進行農藥殘留量的檢驗,檢驗方法使用衛 授食字第1081900612號公告修正的食品中殘留農藥檢驗方法-多重殘留分析方法,檢驗結果為380種農藥殘留皆未檢出,該皮膚敷藥無殘留380種農藥中的任何一種,可以安心塗抹於皮膚。 The inventor also entrusts the National Chiayi University College of Life Sciences Inspection Analysis and Technology Promotion Service Center Food Inspection Group to carry out the inspection of pesticide residues on the skin dressing, and the inspection method uses Sanitation No. 1081900612 Announcement of Shishizi revised the inspection method of pesticide residues in food-multiple residue analysis method. The test results showed that none of the 380 pesticide residues were detected. on the skin.
三、實際成效 3. Actual results
該皮膚敷藥實際的試驗研究自2019年5月15日開始執行,於2019年6月3日收案第一位病患,截至2019年10月10日收案25位病患,排除3位單純甲溝炎患者,對剩餘22位病患之標靶藥物所誘發的皮膚病副作用進行治療與療效分析。該皮膚敷藥委由康馥健康生技有限公司製作,經IRB審查同意,並充分解釋後,取得病患同意並簽署IRB核准版本之病患同意書。 The actual experimental study of the skin dressing began on May 15, 2019, and the first patient was admitted on June 3, 2019. As of October 10, 2019, 25 patients were admitted, and 3 were excluded For patients with simple paronychia, the treatment and curative effect analysis of the side effects of skin diseases induced by targeted drugs were conducted in the remaining 22 patients. The skin dressing committee was produced by Kangfu Health Biotechnology Co., Ltd., approved by the IRB, and after a full explanation, the patient's consent was obtained and the patient's consent form approved by the IRB was signed.
由上表一可以看出,標靶藥物在病患身上所產生最常見的皮膚病副作用是痤瘡樣皮疹(Rash acneiform),在該皮膚敷藥使用之前,有90%以上的病患都受痤瘡樣皮疹所困擾,且毒性級數平均2.30。 It can be seen from the above table 1 that the most common skin disease side effect caused by targeted drugs in patients is acne-like rash (Rash acneiform). Plagued by rash, and the average toxicity grade was 2.30.
在標靶藥物治療而出現皮膚病副作用的期間,將該皮膚敷藥直接濕敷塗抹在身體表面有皮膚病副作用的地方,一天塗抹3次,間隔至少4小時,使用後皮膚病副作用改善結果如下表二所示。 During the period of dermatological side effects caused by targeted drug treatment, apply the skin dressing directly on the body surface where there are dermatological side effects, 3 times a day with an interval of at least 4 hours. After use, the improvement results of dermatological side effects are as follows Table 2 shows.
比較上表一及上表二後可以發現,使用該皮膚敷藥後,無病患出現皮膚病副作用惡化的情況,有痤瘡樣皮疹的病患比例從90.91%顯著下降至31.82%,毒性級數也從2.30下降至0.35,且所有病患的痤瘡樣皮疹毒性級數都被控制在0與1。在其他種類的皮膚病副作用上,例如:乾皮(Dry Skin)、癢(Pruritus)、手足症(Palmar-plantar erythrodysesthesia)及皮膚潰瘍(Skin ulcer)等等,也都有改善,證明該皮膚敷藥確實對於標靶藥物所誘發的皮膚病副作用具有顯著改善效果。 After comparing the above table 1 and the above table 2, it can be found that after using the skin dressing, no patient has worsening side effects of skin diseases, and the proportion of patients with acne-like rash has dropped significantly from 90.91% to 31.82%. The toxicity grade It also dropped from 2.30 to 0.35, and the acneiform rash toxicity grades of all patients were controlled at 0 and 1. Other side effects of skin diseases, such as: dry skin (Dry Skin), itching (Pruritus), hand-foot disease (Palmar-plantar erythrodysesthesia) and skin ulcers (Skin ulcer), etc., have also improved, which proves that the skin application The drug does have a significant improvement effect on the side effects of skin diseases induced by targeted drugs.
為了更直觀的說明該皮膚敷藥所帶來的改善效果,以下展示該皮膚敷藥實際使用前及使用後的照片。為了保護病患的隱私,拍攝病患臉部的照片皆以色塊遮擋眼部。 In order to more intuitively illustrate the improvement effect brought by the skin dressing, the photos before and after the actual use of the skin dressing are shown below. In order to protect the privacy of the patients, the photos taken of the patients' faces are covered with color blocks to cover the eyes.
請參閱第二A圖及第二B圖,第二A圖為肺部惡性腫瘤的病患服用Tarceva的藥物後,在臉部引起的皮膚病副作用,第二B圖則為同一位病患在臉部使用該皮膚敷藥後的效果。 Please refer to the second picture A and the second picture B. The second picture A shows the side effects of skin diseases on the face caused by a patient with lung cancer after taking Tarceva's medicine. The second picture B shows the same patient on the face The effect of using this skin dressing on the face.
請參閱第三A圖及第三B圖,第三A圖為未使用該皮膚敷藥時,在病患臉部的皮膚病副作用,第三B圖則為同一位病患在臉部使用該皮膚敷藥後的效果。 Please refer to the third picture A and the third picture B, the third picture A is the skin disease side effect on the patient's face when the skin dressing is not used, and the third picture B is the same patient using the skin dressing on the face The effect of skin application.
從第二A圖與第二B圖的對比,以及第三A圖與第三B圖的對比,可以發現該皮膚敷藥在臉部的皮膚病副作用具有良好的改善效果,可以有效減少臉部的痤瘡。 From the comparison between the second picture A and the second B picture, and the comparison between the third picture A and the third B picture, it can be found that the skin application drug has a good improvement effect on the side effects of skin diseases on the face, and can effectively reduce the facial side effects. acne.
請參閱第四A圖及第四B圖,第四A圖為未使用該皮膚敷藥時,在病患大腿的皮膚病副作用,第四B圖則為同一位病患在大腿使用該皮膚敷藥後的效果。 Please refer to Figure 4A and Figure 4B. Figure 4A shows the side effects of skin disease on the patient's thigh without using the dressing, and Figure 4B shows the skin dressing on the thigh of the same patient The effect of the medicine.
請參閱第五A圖及第五B圖,第五A圖為未使用該皮膚敷藥時,在病患腹部的皮膚病副作用,第五B圖則為同一位病患在腹部使用該皮膚敷藥後的效果。 Please refer to Figure 5 A and Figure 5 B. Figure 5 A shows the side effects of skin diseases on the patient's abdomen when the skin dressing was not used, and Figure 5 B shows the same patient using the skin dressing on the abdomen The effect of the medicine.
請參閱第六A圖及第六B圖,第六A圖為未使用該皮膚敷藥時,在病患臀部的皮膚病副作用,第六B圖則為同一位病患在臀部使用該皮膚敷藥後的效果。 Please refer to Figure 6A and Figure 6B. Figure 6A shows the side effects of skin disease on the patient's buttocks without using the skin dressing, and Figure 6B shows the same patient using the skin dressing on the buttocks The effect of the medicine.
從第四A圖與第四B圖的對比、第五A圖與第五B圖的對比,以及第六A圖與第六B圖的對比,則可以發現,不只是臉部的皮膚病副作用,該皮膚敷藥在大腿、腹部及臀部等處的皮膚病副作用也都具有良好的改善效果,因此該皮膚敷藥確實可以有效改善標靶藥物引起的皮膚病副作用。 From the comparison between the fourth picture A and the fourth B picture, the comparison between the fifth picture A and the fifth picture B, and the comparison between the sixth picture A and the sixth picture B, it can be found that it is not only the side effects of skin diseases on the face , the skin dressing also has a good improvement effect on the side effects of skin diseases on thighs, abdomen and buttocks, etc., so the skin dressing can indeed effectively improve the side effects of skin diseases caused by targeted drugs.
復請搭配第一圖,藥物產生的毒副作用,中醫觀點認為藥毒內侵,形成血熱內蘊、濕熱毒邪蘊蒸鬱於肌膚,甚者熱毒化火,燔灼營血,溢於肌表。“風、熱、濕、毒、虛”是其主要病理機制,多以清熱解毒藥為主,兼顧補虛藥及解表藥等為治療原則。清熱解毒藥對表現為熱的過度炎症反應(如液體性炎性介質釋放和炎性細胞增殖等過程)具抑制作用,另有抗菌、抗病毒、拮抗炎性細胞因子、抗自由基損傷和保護機體之組織、細胞等作用。 Please refer back to the first picture. Toxic and side effects caused by drugs. From the point of view of traditional Chinese medicine, the drug poison invades internally, forming blood heat, damp heat and poison evil accumulate in the skin, and even heat poison turns into fire, burns the blood and overflows in the skin. surface. "Wind, heat, dampness, poison, and deficiency" are the main pathological mechanisms, and most of them use heat-clearing and detoxifying drugs as the main treatment principles, taking into account tonic drugs and surface-relieving drugs. Heat-clearing and detoxifying drugs have an inhibitory effect on excessive inflammatory reactions manifested as heat (such as the release of liquid inflammatory mediators and inflammatory cell proliferation), and have antibacterial, antiviral, antagonizing inflammatory cytokines, anti-free radical damage and protection Tissues, cells, etc. of the body.
在本發明之實施方式中,該混合液選擇以黃連解毒湯的黃連、黃柏、黃苓及梔子做為基底,再加上桑白皮、苦參根、連翹、龍膽草、石膏及土茯芩等中藥材以加強瀉火解毒、清熱燥濕的功效。該混合液各成分的功效舉例如下:黃連解毒湯最早源于葛洪《肘後備急方》卷二“治傷寒時氣溫病方第十三”,但未出方名。至唐代王燾《外台秘要》中收載的一首方劑並冠名 為黃連解毒湯,方中有黃連、黃芩、黃柏、梔子共四味,清熱瀉火,除濕解毒,主治一切瘡瘍火毒,現代研究中對腦血管疾病、糖尿病、高血壓、癡呆以及皮膚病之使用最多。其在皮膚科如病毒性皮膚病的單純皰疹、帶狀皰疹,皮炎有接觸性皮炎、濕疹、特應性皮炎、激素依賴性皮炎等,紅斑鱗屑性皮膚病如銀屑病,皮膚附屬器疾病痤瘡,脂漏性皮炎,皮膚血管炎如過敏性紫癜等皮膚疾病之應用。黃連解毒湯的瀉火解毒功效主要與抗病原微生物作用、抗細菌毒素作用、解熱抗炎作用及對免疫功能的影響有關,其中對金黃色葡萄球菌有抑菌效果及對細菌毒素均有顯著抗菌作用,具有抗炎、抗過敏及增強吞噬細胞功能的作用。黃連解毒湯主要含有生物鹼、黃酮、環烯醚萜類3大類成分,有效成分如小檗堿、黃芩苷、黃芩素等。主要有效成分為小檗堿,小檗堿的抗菌譜最廣,對革蘭陰性菌、革蘭陽性菌均具有良好的抗菌作用。另一研究指出小檗堿(Berberine)對溶血性鏈球菌,金黃色葡萄球菌,淋球菌和弗氏、志賀氏痢疾桿菌等均有抗菌作用,並有增強白血球吞噬作用,對結核桿菌、鼠疫菌也有不同程度的抑制作用。黃連、黃柏對葡萄球菌、白色念球菌、皮膚絲狀菌、結核桿菌等具有抗菌作用,黃連、黃芩、黃柏、苦參、梔子等皆可產生對金黃色葡萄球菌的抑制作用,黃連、黃柏、黃芩皆可抑制白色念球菌的作用,黃芩、黃連及黃連解毒湯具有抗耐藥性細菌作用,其中黃芩的抗耐藥性細菌譜最廣,對金黃色葡萄球菌、大腸埃希菌、巴氏桿菌等12種耐藥性細菌均有抑制作用。 In the embodiment of the present invention, the mixed liquid is selected from Coptis chinensis, Cortex Phellodendron, Huang Ling and Gardenia as the base, and then added Morus alba, Sophora flavescens root, Forsythia, Gentiana, gypsum and soil Fuqin and other Chinese herbal medicines are used to strengthen the effect of purging fire and detoxifying, clearing away heat and dampness. Examples of the efficacy of each component of the mixture are as follows: Huanglian Jiedu Decoction was first derived from Ge Hong’s "Elbow Reserve Emergency Prescriptions" Volume 2 "The Thirteenth Prescription for Treating Typhoid Fever", but the name of the prescription has not been published. To a prescription recorded in Wang Tao's "Waitai Secret Yao" in the Tang Dynasty and named it It is Huanglian Jiedu Decoction, which contains four flavors of Coptis chinensis, Scutellaria baicalensis, Cortex Phellodendron, and Gardenia. The disease is used the most. In dermatology, such as herpes simplex and herpes zoster of viral skin diseases, dermatitis includes contact dermatitis, eczema, atopic dermatitis, hormone-dependent dermatitis, etc., erythematous and scaly skin diseases such as psoriasis, skin Adnexal disease acne, seborrheic dermatitis, skin vasculitis such as allergic purpura and other skin diseases. The purging fire and detoxification effects of Huanglian Jiedu Decoction are mainly related to the anti-pathogenic microorganisms, anti-bacterial toxins, anti-pyretic and anti-inflammatory effects and the impact on immune function. Among them, it has a significant antibacterial effect on Staphylococcus aureus and a significant effect on bacterial toxins. Antibacterial effect, anti-inflammatory, anti-allergic and enhance the function of phagocytic cells. Huanglian Jiedu Decoction mainly contains three major types of ingredients: alkaloids, flavonoids, and iridoids. The active ingredients are berberine, baicalin, and baicalein. The main active ingredient is berberine, which has the broadest antibacterial spectrum, and has good antibacterial effect on both Gram-negative bacteria and Gram-positive bacteria. Another study pointed out that Berberine (Berberine) has antibacterial effects on hemolytic streptococcus, Staphylococcus aureus, Neisseria gonorrhoeae, Freund's, Shigella dysenteriae, etc., and has enhanced leukocyte phagocytosis. There are also varying degrees of inhibition. Coptidis and Phellodendron have antibacterial effects on Staphylococcus, Candida albicans, skin filamentous bacteria, Mycobacterium tuberculosis, etc. Coptidis, Scutellaria, Phellodendron, Sophora, Gardenia, etc. Scutellaria baicalensis and Scutellaria baicalensis can all inhibit the effect of Candida albicans. Scutellaria baicalensis, Coptis chinensis and Coptis chinensis decoction have anti-drug-resistant bacteria effects, and Scutellaria baicalensis has the widest spectrum of anti-drug-resistant bacteria. 12 kinds of drug-resistant bacteria such as bacilli have inhibitory effect.
苦參中含有苦參鹼、氧化苦參鹼、苦參次鹼、槐果鹼、氧化槐果鹼等多種生物鹼,可以抗金黃色葡萄球菌、沙門氏菌、以及柯薩奇型病毒(CVBⅢ)引起的鏈球菌心肌細胞病變,抑制HBV複製的作用,具有明顯的抗炎、抗過敏、抗病毒、抗寄生蟲、抗心律失常、免疫調節等藥理作用。連翹含有連翹 酯苷、連翹苷、pinoresinol和phylligenin等可抑制TNF-α/IFN-γ激活的人角質細胞中趨化激素的產生,且對大腸桿菌、淋球菌、腦膜炎、沙門氏菌有抑制作用。桑白皮使用甲醇萃取液具有抗發炎作用,其中sanggenon B、albanol B和sanggenon D成分,對LPS刺激的RAW264.7細胞中的NO產生具有抑制作用,albanol B能減少前發炎反應細胞激素的產生和降低nitric oxide synthase(iNOS)和cyclooxvgenase-2(COX-2)的表現量,且桑白皮含有黃酮類、生物鹼和芪類,具有抗菌、美白、細胞毒性、抗發炎和抗高血脂的特性。龍膽草在老鼠皮膚試驗中,已知可緩解皮膚病變,如表面粗糙、脫落和結痂,以及防止降低紅斑和黑色素指數。土茯苓能保護皮膚纖維母細胞對抗紫外線誘發皮膚的老化,也對抗氧化壓力具有保護作用。石膏主要的成分為CaSO4,可以維持皮膚的正常含水量,可以增加細胞內鈣離子的濃度、protein kinase C(PKC)的活性、extracellular signal-regulated kinase(ERK)和cAMP response element binding protein(CREB)磷酸化的濃度。 Sophora flavescens contains matrine, oxymatrine, matrine, sophocarpine, oxysophocarpine and other alkaloids, which can resist Staphylococcus aureus, Salmonella, and Coxsackie virus (CVBⅢ) streptococcal cardiomyocyte lesion, inhibit HBV replication, has obvious anti-inflammatory, anti-allergic, anti-viral, anti-parasitic, anti-arrhythmia, immune regulation and other pharmacological effects. Forsythia contains forsythiaside, forsythin, pinoresinol and phylligenin, etc., which can inhibit the production of chemotactic hormones in human keratinocytes activated by TNF-α/IFN-γ, and have inhibitory effects on Escherichia coli, Neisseria gonorrhoeae, meningitis, and Salmonella. Morus alba extract with methanol has anti-inflammatory effect, and the components of sanggenon B, albanol B and sanggenon D can inhibit the production of NO in LPS-stimulated RAW264.7 cells, and albanol B can reduce the production of cytokines in the pro-inflammatory response and reduce the expression of nitric oxide synthase (iNOS) and cyclooxvgenase-2 (COX-2), and Morus alba contains flavonoids, alkaloids and stilbenes, which have antibacterial, whitening, cytotoxic, anti-inflammatory and anti-hyperlipidemic effects characteristic. Gentiana is known to relieve skin lesions such as rough surface, flaking and crusting, as well as prevent reduction of erythema and melanin index in mouse skin tests. Smilax smilax protects dermal fibroblasts against UV-induced skin aging and also has protective effects against oxidative stress. The main component of gypsum is CaSO 4 , which can maintain the normal water content of the skin, increase the concentration of intracellular calcium ions, the activity of protein kinase C (PKC), extracellular signal-regulated kinase (ERK) and cAMP response element binding protein (CREB ) concentration of phosphorylation.
根據以上說明,也可以得知該混合液製成的該皮膚敷藥確實具有改善皮膚病副作用的功效。 According to the above description, it can also be known that the skin dressing made of the mixed solution does have the effect of improving the side effects of skin diseases.
綜合上述實施例之說明,當可充分瞭解本發明之操作、使用及本發明產生之功效,惟以上所述實施例僅係為本發明之較佳實施例,當不能以此限定本發明實施之範圍,即依本發明申請專利範圍及發明說明內容所作簡單的等效變化與修飾,皆屬本發明涵蓋之範圍內。 Based on the description of the above-mentioned embodiments, it is possible to fully understand the operation of the present invention, use and the effect that the present invention produces, but the above-mentioned embodiments are only preferred embodiments of the present invention, and should not be used to limit the implementation of the present invention. The scope, that is, the simple equivalent changes and modifications made according to the patent scope of the present invention and the content of the description of the invention, all fall within the scope of the present invention.
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