TWI744735B - Composition for chronic wound healing - Google Patents
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本發明關於一種具有慢性傷口癒合功效之組合物，具體而言，本發明關於一種具有慢性傷口癒合功效之組合物及該組合物用於製備治療慢性傷口藥劑之用途。The present invention relates to a composition with chronic wound healing effect. Specifically, the present invention relates to a composition with chronic wound healing effect and the use of the composition for preparing a medicament for treating chronic wounds.
隨著人口結構老化，慢性疾病已成為健康照護的主軸，其中慢性傷口的照護是非常重要的一環。慢性傷口是指傷口在經過合宜治療經一預定的時間後，仍無法達到一般傷口結構上和外觀上的癒合，迄今仍無有效的治療藥劑。慢性傷口種類包括長期臥床所造成的褥瘡或壓瘡、糖尿病人的傷口潰瘍、末梢血管阻塞的肢體壞疽、動脈或靜脈障礙所引起的潰瘍、癌症病人的不癒傷口、急性傷口感染所引起的慢性癒合不良等等。With the aging of the population structure, chronic diseases have become the main axis of health care, of which the care of chronic wounds is a very important part. Chronic wounds refer to wounds that have been properly treated for a predetermined period of time, but they still fail to heal in general wound structure and appearance, and there is still no effective treatment agent. Types of chronic wounds include bedsores or pressure ulcers caused by long-term bed rest, wound ulcers of diabetic patients, gangrene of peripheral blood vessels, ulcers caused by arterial or venous disorders, unhealed wounds of cancer patients, and chronic wounds caused by acute wound infections. Poor healing and so on.
類葉升麻苷(acteoside)存在於中草藥之一種活性成分，具有脂肪酶抑製功效，已知具有抗菌、抗發炎、抗病毒、抗氧化、神經保護等活性。Acteoside is an active ingredient in Chinese herbal medicine. It has a lipase inhibitory effect and is known to have antibacterial, anti-inflammatory, antiviral, antioxidant, and neuroprotective activities.
類葉升麻苷被報導為有效的抗微生物成分，已知對於金黃葡萄球菌(Staphylococcus aureus )具有良好的抗菌功效(Guillermo等人，1999，Journal of Ethnopharmacology 66(1)：75-8)。類葉升麻苷亦具有良好的抗發炎效果(Speranza等人，2009，Journal of biological regulators and homeostatic agents 23(3)：189-95.)。此外，2016年01月06日公告之中國專利授權公告第103816169B號，揭露類葉升麻苷可用於製備防治血管性癡呆，對低糖低氧造成之細胞缺血缺氧具保護和治療作用。又，2016年01月16日公開之中華民國專利公開號第201601739號，提供一種桂花萃取物的製備方法，以類葉升麻苷為主要活性成份，具有抗氧化、皮膚保養、抗微生物及抗發炎等功效。但並未有任何報導可用於治療慢性傷口癒合。Lacteroside has been reported as an effective antimicrobial ingredient and is known to have good antibacterial effects against Staphylococcus aureus (Guillermo et al., 1999, Journal of Ethnopharmacology 66(1):75-8). Cimicifugaoside also has a good anti-inflammatory effect (Speranza et al., 2009, Journal of biological regulators and homeostatic agents 23(3): 189-95.). In addition, the Chinese Patent Grant Announcement No. 103816169B announced on January 6, 2016 discloses that cohodoside can be used to prepare and prevent vascular dementia, and has protective and therapeutic effects on cell ischemia and hypoxia caused by low glucose and hypoxia. In addition, the Republic of China Patent Publication No. 201601739, published on January 16, 2016, provides a preparation method of Osmanthus fragrans extract, which uses cimicifuga glycosides as the main active ingredient, which has antioxidant, skin care, antimicrobial and antimicrobial properties. Inflammation and other effects. But there are no reports that it can be used to treat chronic wound healing.
本發明係提供一種新穎之組合物，其具有慢性傷口癒合功效，主要由下列三組份組成：(1) 一種抗發炎劑，係選自類葉升麻苷、異類葉升麻苷及其組合組成之群，(2)一種收斂劑，係選自沒食子酸、次沒食子酸、其鹽類及其組合組成之群，以及(3)一種清涼劑，係選自龍腦、薄荷腦及其組合組成之群，並視需要與一種或以上醫藥上可接受之載劑組合。The present invention provides a novel composition which has chronic wound healing effect and mainly consists of the following three components: (1) An anti-inflammatory agent selected from the group consisting of cohodosides, cohodosides and combinations thereof The group consisting of (2) an astringent, selected from the group consisting of gallic acid, hypogallic acid, its salts and combinations thereof, and (3) a refreshing agent, selected from the group consisting of borneol and peppermint A group consisting of brain and its combination, and optionally combined with one or more pharmaceutically acceptable carriers.
另一方面，本發明提供此組合物用於製備治療慢性傷口藥劑之用途。In another aspect, the present invention provides the use of this composition for preparing a medicament for treating chronic wounds.
根據本發明之一實施例，慢性傷口係指糖尿病傷口。According to an embodiment of the present invention, chronic wounds refer to diabetic wounds.
根據本發明之一實施例，其中三組份之當量配比為(1)抗發炎劑：(2)收斂劑：(3)清涼劑為1:0.1-10:0.1-10。According to an embodiment of the present invention, the equivalent ratio of the three components is (1) anti-inflammatory agent: (2) astringent: (3) cooling agent 1:0.1-10:0.1-10.
根據本發明之一較佳實施例，其中三組份之當量配比為(1) 抗發炎劑：(2)收斂劑：(3)清涼劑為1:0.5-5:0.5-5。According to a preferred embodiment of the present invention, the equivalent ratio of the three components is (1) anti-inflammatory agent: (2) astringent: (3) cooling agent 1:0.5-5:0.5-5.
根據本發明之一特定實施例，其中三組份之當量配比為(1)抗發炎劑：(2)收斂劑：(3)清涼劑為約1:1:1。According to a specific embodiment of the present invention, the equivalent ratio of the three components is (1) anti-inflammatory agent: (2) astringent: (3) cooling agent is about 1:1:1.
根據本發明之實施例，其中該抗發炎劑為具有下列式I結構之類葉升麻苷或其異構物：
根據本發明之實施例，其中該收斂劑為具有下列式II結構之沒食子酸：
根據本發明之實施例，其中該收斂劑為沒食子酸或次沒食子酸之鹽類，較佳為鉍鹽。According to an embodiment of the present invention, the astringent is a salt of gallic acid or hypogallic acid, preferably a bismuth salt.
根據本發明之最佳實施例，其中該收斂劑為具有下列式IIa結構之次沒食子酸鉍：
根據本發明之實施例，其中該清涼劑為具有下列式IIIa結構之龍腦：
根據本發明之實施例，其中該清涼劑為具有下列式IIIb結構之薄荷腦：
再一方面，本發明提供一種具有治療慢性傷口癒合功效之醫藥組合物，主要由下列三組份組成：(1) 類葉升麻苷，(2)次沒食子酸鉍，以及(3)龍腦，並視需要與一種或以上醫藥上可接受之載劑組合。In another aspect, the present invention provides a pharmaceutical composition with the healing effect of treating chronic wounds, which is mainly composed of the following three components: (1) cohodoside, (2) bismuth subgallate, and (3) Borneol, and optionally combined with one or more pharmaceutically acceptable carriers.
根據本發明，其中該醫藥組合物中三組份之當量配比為(1)類葉升麻苷：(2)次沒食子酸鉍：(3)龍腦為1:0.1-10:0.1-10；較佳為1:0.5-5:0.5-5。According to the present invention, the equivalent ratio of the three components in the pharmaceutical composition is (1) cimicifuga glycoside: (2) bismuth subgallate: (3) borneol is 1:0.1-10:0.1 -10; preferably 1:0.5-5:0.5-5.
根據本發明之一實施例，其中該醫藥組合物中三組份之當量配比為(1)類葉升麻苷：(2)次沒食子酸鉍：(3)龍腦為約1: 1: 1。According to an embodiment of the present invention, the equivalent ratio of the three components in the pharmaceutical composition is (1) cimicifugaoside: (2) bismuth subgallate: (3) borneol is about 1: 1: 1.
根據本發明，該醫藥組合物包含重量比(1) 0.05%-10%之類葉升麻苷，(2) 0.05%-10%之次沒食子酸鉍，及(3) 0.02%-5%之龍腦，以及醫藥上可接受載體。According to the present invention, the pharmaceutical composition contains the weight ratio of (1) 0.05%-10% of cimicifugaoside, (2) 0.05%-10% bismuth gallate, and (3) 0.02%-5 % Of borneol, and a pharmaceutically acceptable carrier.
本發明之該等及其它方面，可藉由以下之較佳具體實施例之描述以及圖式，得以更為明晰；即便其中可能會有變化或修飾，但不背離本發明所揭露之新穎觀念的精神及範疇。These and other aspects of the present invention can be made clearer by the following descriptions and drawings of the preferred embodiments; even though there may be changes or modifications, they do not deviate from the novel concepts disclosed by the present invention Spirit and category.
除非另有定義，所有本文所用之技術性及科學性術語，對於屬於本發明領域之具有通常知識者而言，皆具有與其所習知者相同意義。Unless otherwise defined, all technical and scientific terms used herein have the same meaning as those who are acquainted with in the field of the present invention.
除非文中有清楚指明者，於本文中所使用之單數形式「一」、「一種」、及「該」之涵義均為包括「至少一種」的複數形式。因此，例如，當提及「一成分」時，包括複數個該等成分及對該領域具有通常知識者所知之同等物。Unless clearly specified in the text, the meanings of the singular forms "a", "a", and "the" used in this article all include the plural forms of "at least one". Therefore, for example, when referring to "an ingredient", it includes a plurality of such ingredients and equivalents known to those with ordinary knowledge in the field.
於本文中所使用之名詞「慢性傷口」係指傷口在經過合宜治療經一預定的時間後，仍無法達到一般傷口結構上和外觀上的癒合。慢性傷口種類包括長期臥床所造成的褥瘡或壓瘡、糖尿病傷口潰瘍、末梢血管阻塞的肢體壞疽、動脈或靜脈障礙所引起的潰瘍、癌症病人的不癒傷口、急性傷口感染所引起的慢性癒合不良。根據本發明，本發明組合物顯示對於慢性傷口之皮膚症狀傷口具有癒合之效，尤其是對糖尿病傷口特別有效。The term "chronic wound" as used in this article refers to a wound that has been properly treated for a predetermined period of time, but the structure and appearance of the general wound cannot be healed. Types of chronic wounds include bedsores or pressure ulcers caused by long-term bed rest, diabetic wound ulcers, gangrene of peripheral blood vessels, ulcers caused by arterial or venous disorders, unhealed wounds of cancer patients, and chronic poor healing caused by acute wound infections . According to the present invention, the composition of the present invention is shown to have a healing effect on chronic wounds with skin symptoms, especially for diabetic wounds.
於本文中所使用之名詞「治療」，包括「處理」或「促進」之意，意指改善症狀。The term "treatment" used in this article includes the meaning of "treating" or "promoting", which means to improve symptoms.
於本文中所使用之名詞「患者」包含人類、及動物，特別是哺乳動物。The term "patient" as used herein includes humans, and animals, especially mammals.
於本文中所使用之名詞「醫藥上可接受之載劑」係指一般醫藥上常用之技術可用於製備醫藥組合物之稀釋劑、賦形劑及其類似物。根據本發明，可調製成藥品、化粧品或醫藥材料之型式。根據本發明，可製成局部方式塗敷之形式，例如，噴霧形式。噴霧形式包含噴劑及液劑；或半固體或固體形式，較佳為具有動態黏度大於水者之固體形式。適當配方包括但不限於懸浮液、乳化液、乳膏、軟膏、擦劑等。較佳者，係呈軟膏形式。本發明醫藥組合物不論呈何種形式，亦可含有潤膚劑、香料或顏料，以提高其對於各種用途之可接受性。The term "pharmaceutically acceptable carrier" as used herein refers to diluents, excipients, and the like that can be used to prepare pharmaceutical compositions by common techniques in medicine. According to the present invention, it can be adjusted into the form of medicines, cosmetics or medical materials. According to the present invention, it can be made into a form of local application, for example, a spray form. Spray forms include sprays and liquids; or semi-solid or solid forms, preferably solid forms with dynamic viscosity greater than water. Appropriate formulations include, but are not limited to, suspensions, emulsions, creams, ointments, liniments and the like. Preferably, it is in the form of an ointment. No matter what form the pharmaceutical composition of the present invention is in, it can also contain emollients, fragrances or pigments to improve its acceptability for various uses.
於本文中所使用之名詞「治療有效量」，意指在症狀處理上可有效治療傷口之劑量。可依患者或傷口之需，依一般醫藥上常用之技術或臨床知識使用適當劑量，並可依照施予的方式及治療的情況，包括年齡、體重、症狀、治療效果、施用方式及治療時間調整。As used herein, the term "therapeutically effective dose" means a dose that can effectively treat wounds in the management of symptoms. The appropriate dosage can be used according to the needs of the patient or wound, according to common medical techniques or clinical knowledge, and can be adjusted according to the method of administration and treatment, including age, weight, symptoms, treatment effect, administration method, and treatment time. .
本發明提供一種具有慢性傷口癒合功效之組合物，主要由下列三組份組成：(1)一種抗發炎劑，係選自類葉升麻苷、異類葉升麻苷及其組合組成之群， (2)一種收斂劑，係選自沒食子酸、次沒食子酸、其鹽類及其組合組成之群，以及(3)一種清涼劑，係選自龍腦、薄荷腦及其組合組成之群，並視需要與一種或以上醫藥上可接受之載劑組合。本發明亦提供此組合物用於製備治療慢性傷口藥劑之用途，尤指糖尿病傷口。The present invention provides a composition with chronic wound healing effect, which is mainly composed of the following three components: (1) an anti-inflammatory agent selected from the group consisting of cohodosides, cohodosides and combinations thereof, (2) An astringent, selected from the group consisting of gallic acid, hypogallic acid, its salts and combinations thereof, and (3) a cooling agent, selected from the group consisting of borneol, menthol and combinations thereof It can be combined with one or more pharmaceutically acceptable carriers as needed. The present invention also provides the use of the composition for preparing a medicament for treating chronic wounds, especially diabetic wounds.
根據本發明之實施例顯示，本發明組合物對於高糖環境下培養之細胞增生及遷移具有顯著之增進功效，但單一組成分或任二組合則並無功效。尤其本發明組合物對於低糖環境培養相對並無增進功效，顯示本發明組合物對於糖尿病傷口癒合之特殊功效，進一步可支持其慢性傷口癒合之功效。According to the embodiments of the present invention, the composition of the present invention has a significant effect on enhancing cell proliferation and migration in a high-glycemic environment, but a single component or any combination of two has no effect. In particular, the composition of the present invention is relatively ineffective for culture in a low-sugar environment, showing that the composition of the present invention has a special effect on diabetic wound healing, and can further support its chronic wound healing effect.
根據本發明，可依一般習知技術製備適當含量之組合物，其中實施例可包括各成分的當量範圍是： (1) 抗發炎劑：1； (2) 收斂劑：0.1-10；較佳為0.5-5。 (3) 清涼劑：0.1-10；較佳為0.5-5。According to the present invention, a composition with an appropriate content can be prepared according to general known techniques, wherein the examples can include the equivalent range of each ingredient: (1) Anti-inflammatory agent: 1; (2) Astringent: 0.1-10; preferably 0.5-5. (3) Cooling agent: 0.1-10; preferably 0.5-5.
根據本發明之一特定實施例，其中三組份之當量配比為(1)抗發炎劑：(2)收斂劑：(3)清涼劑為約1:1:1。According to a specific embodiment of the present invention, the equivalent ratio of the three components is (1) anti-inflammatory agent: (2) astringent: (3) cooling agent is about 1:1:1.
本發明議題提供一種具有治療慢性傷口癒合功效之醫藥組合物，主要由下列三組份組成：(1) 類葉升麻苷，(2)次沒食子酸鉍，以及(3)龍腦，並視需要與一種或以上醫藥上可接受之載劑組合。即如商標為糖足樂7TM (NuDFC7TM ) 尚未上市之商品。The subject of the present invention provides a medicinal composition with the healing effect of treating chronic wounds, which is mainly composed of the following three components: (1) cimicifugaoside, (2) bismuth subgallate, and (3) borneol, If necessary, it can be combined with one or more pharmaceutically acceptable carriers. That is, a product that has not yet been marketed if the trademark is Tangzule 7 TM (NuDFC7 TM ).
根據本發明，其中該醫藥組合物中三組份之當量配比為(1)類葉升麻苷：(2)次沒食子酸鉍：(3)龍腦為1:0.1-10:0.1-10；較佳為1:0.5-5:0.5-5。其中之特定實施例為約1:1:1。According to the present invention, the equivalent ratio of the three components in the pharmaceutical composition is (1) cimicifuga glycoside: (2) bismuth subgallate: (3) borneol is 1:0.1-10:0.1 -10; preferably 1:0.5-5:0.5-5. A specific example is about 1:1:1.
根據本發明，其中該醫藥組合物包含重量比(1)0.05%-10%類葉升麻苷， (2) 0.05%-10%之次沒食子酸鉍：(3) 0.02%-5%之龍腦，以及醫藥上可接受載體。According to the present invention, wherein the pharmaceutical composition comprises (1) 0.05%-10% cohodoside by weight, (2) 0.05%-10% bismuth gallate: (3) 0.02%-5% Borneol, and a pharmaceutically acceptable carrier.
根據本發明之一實施例，其中該醫藥組合物包含重量比(1) 0.1%-5%之類葉升麻苷，(2) 0.06%-6%之次沒食子酸鉍，及(3) 0.03%-3%之龍腦，以及醫藥上可接受載體。According to an embodiment of the present invention, wherein the pharmaceutical composition comprises a weight ratio of (1) 0.1%-5% of cimicifugaoside, (2) 0.06%-6% bismuth gallate, and (3) ) 0.03%-3% Borneol, and a pharmaceutically acceptable carrier.
根據本發明之一較佳實施例，其中該醫藥組合物包含(1) 0.3%-5%之類葉升麻苷，(2) 0.5%-5%之次沒食子酸鉍，及(3) 0.5%-1%之龍腦，以及醫藥上可接受載體。According to a preferred embodiment of the present invention, wherein the pharmaceutical composition comprises (1) 0.3%-5% of cimicifugain, (2) 0.5%-5% of bismuth gallate, and (3) ) 0.5%-1% Borneol, and a pharmaceutically acceptable carrier.
根據本發明，其中該組合物可包含一適當賦形劑而製成外用藥劑形式、化粧品形式或醫藥材料形式之組合物。According to the present invention, the composition may include an appropriate excipient to prepare a composition in the form of external pharmaceuticals, cosmetics or medical materials.
根據本發明，其中該組合物尚包含一治療劑，例如其他抗發炎劑、抗菌劑或其他治療藥劑。According to the present invention, the composition further contains a therapeutic agent, such as other anti-inflammatory agents, antibacterial agents or other therapeutic agents.
以上述發明說明以及下列實施例說明本發明，但並非用以限制本發明之範圍。The above description of the invention and the following examples illustrate the present invention, but they are not intended to limit the scope of the present invention.
藥劑： Pharmacy:
(1)類葉升麻苷(Acteoside，以A為代號)：購自美國Sigma-Aldrich(St.Louis,MO,USA)。 (1) Acteoside (Acteoside, code name A): purchased from Sigma-Aldrich (St. Louis, MO, USA).
(2)次沒食子酸鉍(Bismuth subgallate，以BSG為代號)：美國Sigma-Aldrich(St.Louis,MO,USA)。 (2) Bismuth subgallate (Bismuth subgallate, BSG as the code name): Sigma-Aldrich (St. Louis, MO, USA).
(3)龍腦(Borneol，以BO為代號)：美國Sigma-Aldrich(St.Louis,MO,USA)。 (3) Borneol (Borneol, the code name is BO): Sigma-Aldrich (St. Louis, MO, USA).
根據本發明可依下列組成製備組合物：
進行以下細胞實驗之本發明組合物各組份含量為： (1)類葉升麻苷16.0μM (0.01μg/μl)，即0.1%； (2)次沒食子酸鉍14.2μM (0.0056μg/μl)，即0.056% ；及 (3)龍腦BO 18.8μM (0.0029μg/μl)，即0.029%。The content of each component of the composition of the present invention for the following cell experiments is: (1) Cimicifugaoside 16.0μM (0.01μg/μl), which is 0.1%; (2) Bismuth subgallate 14.2μM (0.0056μg/μl), which is 0.056%; and (3) Borneol BO 18.8μM (0.0029μg/μl), which is 0.029%.
細胞培養(Cell culture) ：Cell culture:
將人類皮膚原纖細胞(human dermal fibroblast,HDF cells)或皮膚角質細胞(human keratinocytes,HaCaT cells)，培養於37℃的潮濕培養箱中，在空氣為5%二氧化碳及95%氧氣的環境下，放置在Dulbecco氏修飾Eagle培養基（DMEM）中，並添加葡萄糖、10%胎牛血清、100 IU/mL盤尼西林、100 μg/mL鏈黴素、2mM丙酮酸鈉和1%非必須胺基酸(NEAA)。該培養基每兩天更換一次。進行繼代培養時，在以0.1%胰蛋白酶（Trypsin）-EDTA混合液作用後，收集細胞並以1:10的比例稀釋重新培養。使用於研究中的細胞，代數介於12至40代之間。在以藥物處理前24小時，開始種植細胞並放置24小時。對照組維持於培養基並添加藥物。在此培養條件下，不影響細胞生長與分化。Culture human dermal fibroblast ( HDF cells) or skin keratinocytes ( HaCaT cells) in a humidified incubator at 37°C in an environment where the air is 5% carbon dioxide and 95% oxygen. Placed in Dulbecco's modified Eagle medium (DMEM), and added glucose, 10% fetal calf serum, 100 IU/mL penicillin, 100 μg/mL streptomycin, 2mM sodium pyruvate and 1% non-essential amino acid (NEAA) ). The medium is changed every two days. For subculture, after using a 0.1% Trypsin-EDTA mixture, the cells are collected and diluted at a ratio of 1:10 to re-culture. The cells used in the study are between 12 and 40 generations. 24 hours before the drug treatment, the cells were planted and left for 24 hours. The control group was maintained in the culture medium and added with drugs. Under this culture condition, cell growth and differentiation are not affected.
實例1 細胞生長分析 (Cell Proliferation Assay)Example 1 Cell Proliferation Assay
以HaCaT細胞3 X 105 培養於標添加25 mM之葡萄糖，培養於12孔之培養皿培養48小時。細胞生長及存活狀態以CCK-8試劑套組 (Dojindo Molecular Technologies, Kumamoto, Japan) 進行分析，在每格中加入5μL CCK-8溶液並於37°C下培養一小時，再用分光度計Microplate reader (SpectraMax, Molecular Device, USA)測定450 nm吸收，樣本與對照組數值相比進行實驗結果分析。測試之實驗組包括： (1) Con :對照組； (2) A 16.0μM； (3) BO 18.8μM； (4) BSG 14.2μM； (5) BO 18.8μM +A 16.0μM； (6) BSG 14.2μM +A 16.0μM； (7) BO 18.8µM + BSG 14.2μM； (8) All (A 16.0μM + BO 18.8μM + BSG 14.2μM)。HaCaT cells were cultured in 3×10 5 with 25 mM glucose, and cultured in a 12-well petri dish for 48 hours. Cell growth and viability were analyzed with the CCK-8 reagent kit (Dojindo Molecular Technologies, Kumamoto, Japan). Add 5μL of CCK-8 solution to each cell and incubate at 37°C for one hour, then use the Microplate spectrometer The reader (SpectraMax, Molecular Device, USA) measures the absorption at 450 nm, and compares the sample with the control group to analyze the experimental results. The experimental groups tested include: (1) Con: control group; (2) A 16.0μM; (3) BO 18.8μM; (4) BSG 14.2μM; (5) BO 18.8μM + A 16.0μM; (6) BSG 14.2μM + A 16.0μM; (7) BO 18.8μM + BSG 14.2μM; (8) All (A 16.0μM + BO 18.8μM + BSG 14.2μM).
培養48小時候之細胞增生結果如圖1，顯示本發明組合物(All; A 16.0μM + BO 18.8μM + BSG 14.2μM)最佳，提供不可預期之顯著促進細胞增生功效(p > 0.05)，但單一組成份則無效果，或任二者之組合效果不如三者之組合。The results of cell proliferation after 48 hours of culture are shown in Figure 1, which shows that the composition of the present invention (All; A 16.0μM + BO 18.8μM + BSG 14.2μM) is the best, providing unexpectedly significant cell proliferation promoting effect (p> 0.05), but A single set of ingredients has no effect, or any combination of the two is not as effective as a combination of the three.
實例2 低糖與高糖環境細胞培養分析比較 (Comparison in Cell Proliferation Assay)Example 2 Comparison in Cell Proliferation Assay between low-sugar and high-sugar environment cell culture
以HaCaT細胞3 X 105 培養於添加5mM、25 mM之葡萄糖，培養於12孔之培養皿48小時，添加本發明組合物(All: A 16.0μM + BO 18.8μM + BSG 14.2μM)觀察其細胞增生狀況。HaCaT cells were cultured in 3×10 5 with 5mM, 25 mM glucose, cultured in a 12-well petri dish for 48 hours, and the cells were observed by adding the composition of the present invention (All: A 16.0μM + BO 18.8μM + BSG 14.2μM) Hyperplasia status.
培養48小時候之細胞增生結果如圖2，顯示本發明組合物(A 16.0μM + BO 18.8μM + BSG 14.2μM)對高糖培養(25 mM)之細胞增長有顯著之相乘增進功效，但對低糖(5 mM)之細胞增生並無顯著促進功效。The results of cell proliferation after 48 hours of culture are shown in Figure 2, which shows that the composition of the present invention (A 16.0μM + BO 18.8μM + BSG 14.2μM) has a significant synergistic effect on cell growth in high glucose culture (25 mM), but it is not Low-sugar (5 mM) cell proliferation does not have a significant effect on promoting cell proliferation.
實例3 細胞遷移分析 (Cell Migration Assay)Example 3 Cell Migration Assay
以HaCaT細胞1 X 105 培養於添加25 mM之葡萄糖，培養於24孔之培養皿48小時，添加如下列之藥物，觀察其細胞遷移狀態： Con :對照組； BO 18.8μM +A 16.0μM； BSG 14.2μM +A 16.0μM； BO 18.8μM + BSG 14.2μM； All: A 16.0μM + BO 18.8μM + BSG 14.2μM。HaCaT cells were cultured at 1×10 5 with 25 mM glucose, cultured in a 24-well petri dish for 48 hours, and the following drugs were added to observe the cell migration status: Con: control group; BO 18.8μM + A 16.0μM; BSG 14.2μM + A 16.0μM; BO 18.8μM + BSG 14.2μM; All: A 16.0μM + BO 18.8μM + BSG 14.2μM.
48小時培養後之各組細胞遷移結果影像如圖3A，並以對照組結果為1，與其他組比較如圖3B，顯示本發明組合物(A 16.0μM + BO 18.8μM + BSG 14.2μM)對高糖培養(25 mM)之細胞遷移有促進功效，但BO 18.8μM、BSG 14.2μM、或三組份之任二組合則無促進功效，可推知本發明組合物對於糖尿傷口癒合具有不可預期之治療效果，並進一步支持其慢性傷口癒合之效。The results of cell migration in each group after 48 hours of culture are shown in Figure 3A, and the result of the control group is 1, compared with other groups as shown in Figure 3B, showing that the composition of the present invention (A 16.0μM + BO 18.8μM + BSG 14.2μM) High-glucose culture (25 mM) can promote cell migration, but BO 18.8μM, BSG 14.2μM, or any combination of the three components has no promoting effect. It can be inferred that the composition of the present invention has unexpected effects on diabetic wound healing. Therapeutic effect, and further support its chronic wound healing effect.
無without
圖1顯示本發明組合物針對高糖(20mM)環境培養HaCaT細胞48小時促進細胞增生之結果 (Con :對照組；A 16.0μM； BO 18.8μM；BSG 14.2μM； BO 18.8μM +A 16.0μM； BSG 14.2μM +A 16.0μM；BO 18.8μM + BSG 14.2μM；All (A 16.0μM + BO 18.8μM + BSG 14.2μM) ；*顯示差異顯著，p>0.05)。Figure 1 shows the results of the composition of the present invention for promoting cell proliferation by culturing HaCaT cells in a high glucose (20mM) environment for 48 hours (Con: control group; A 16.0μM; BO 18.8μM; BSG 14.2μM; BO 18.8μM + A 16.0μM; BSG 14.2μM + A 16.0μM; BO 18.8μM + BSG 14.2μM; All (A 16.0μM + BO 18.8μM + BSG 14.2μM); * shows a significant difference, p>0.05).
圖2顯示本發明組合物(All, A 16.0μM + BO 18.8μM + BSG 14.2μM)針對低糖(5mM)與高糖(25mM)環境培養HaCaT細胞48小時細胞增生之比較， *顯示差異顯著，p>0.05 (5: 5mM 葡萄糖；25: 25mM 葡萄糖；5+All: 5mM 葡萄糖並添加本發明組合物(A 16.0μM + BO 18.8μM + BSG 14.2μM)；；25+All: 25mM 葡萄糖並添加本發明組合物(A 16.0μM + BO 18.8μM + BSG 14.2μM))。Figure 2 shows the comparison of the composition of the present invention (All, A 16.0μM + BO 18.8μM + BSG 14.2μM) against the proliferation of HaCaT cells cultured in a low-sugar (5mM) and high-sugar (25mM) environment for 48 hours. *It shows a significant difference, p >0.05 (5: 5mM glucose; 25: 25mM glucose; 5+All: 5mM glucose with addition of the present composition (A 16.0μM + BO 18.8μM + BSG 14.2μM);; 25+All: 25mM glucose with addition of the present invention Composition (A 16.0 μM + BO 18.8 μM + BSG 14.2 μM)).
圖3A顯示本發明組合物(All)與對照組等於高糖(25mM)環境培養HaCaT細胞48小時細胞遷移之影像(Con :對照組；BO 18.8μM；BSG 14.2μM； BO 18.8μM +A 16.0μM； BSG 14.2μM +A 16.0μM；BO 18.8μM + BSG 14.2μM；All (A 16.0μM + BO 18.8μM + BSG 14.2μM))。Figure 3A shows the image of cell migration of HaCaT cells cultured in the composition of the present invention (All) and the control group equal to high glucose (25mM) for 48 hours (Con: control group; BO 18.8μM; BSG 14.2μM; BO 18.8μM + A 16.0μM ; BSG 14.2 μM + A 16.0 μM; BO 18.8 μM + BSG 14.2 μM; All (A 16.0 μM + BO 18.8 μM + BSG 14.2 μM)).
圖3B顯示本發明組合物(All)與對照組等於高糖(25mM)環境培養HaCaT細胞48小時，以對造組組胞細胞為1.0，相對於其他實驗組胞細胞增生比之比較(Con :對照組；A 16.0μM； BO 18.8μM；BSG 14.2μM； BO 18.8μM +A 16.0μM； BSG 14.2μM +A 16.0μM；BO 18.8μM + BSG 14.2μM；All (A 16.0μM + BO 18.8μM + BSG 14.2μM))。Figure 3B shows the comparison between the composition of the present invention (All) and the control group in an environment equal to high glucose (25mM) for 48 hours to culture HaCaT cells, with a cell proliferation ratio of 1.0 compared to other experimental groups (Con: Control group; A 16.0μM; BO 18.8μM; BSG 14.2μM; BO 18.8μM + A 16.0μM; BSG 14.2μM + A 16.0μM; BO 18.8μM + BSG 14.2μM; All (A 16.0μM + BO 18.8μM + BSG 14.2μM)).
無without
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Non-Patent Citations (3)
| Title |
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| Adv Skin Wound Care. 2007 Sep;20(9 Pt 1):485-492 * |
| SUPPLEMENTARY MATERIAL, 2018 Volume 41 Issue 10 Pages 1530-1536 |
| SUPPLEMENTARY MATERIAL, 2018 Volume 41 Issue 10 Pages 1530-1536; * |
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