TWI474818B - Treatment of urinary system of medical composition - Google Patents
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本發明係與醫藥組成物相關，其更進一步係使將碳材料載於一含水載體，使兩者形成藥用上可接受之載有碳材料之含水載體而用以治療泌尿系統之醫藥組成物。The present invention relates to a pharmaceutical composition, which further comprises a pharmaceutical composition for treating a urinary system by loading a carbon material on an aqueous carrier such that the two form a pharmaceutically acceptable aqueous carrier carrying the carbon material. .
按，習知常見的泌尿系統疾病多為膀胱炎或尿道感染，該泌尿系統可能因為細菌、化學藥物、放射線、抗癌藥物或由外源性細菌感染所造成，亦或者會因為施以藥物而造成抵抗力降低以致細菌入侵所造成，而其特好發於女性或使用導尿管患者，而其最簡單之判斷方法係藉由菌尿症現象出現與否來決定是否產生膀胱炎，即每毫升尿液細菌量大於105 CFU，其中，男性尿道遠端2公分處有細菌寄居者約為98%，5公分處為49%；而女性其細菌寄居之比率可能更高，因此，當尿液細菌量過高時即有膀胱炎或腎盂腎炎產生；並可參考2007年台灣加護病房院內感染之統計發現，泌尿道感染佔院內感染37.5%為最多，且不論是醫學中心或區域醫院，泌尿道感染高居台灣加護病房院內感染第一位，所以目前所有年齡層中的細菌感染所造成之泌尿系統疾病，可見仍以泌尿道感染高居第一位。又，導尿管***術或膀胱鏡檢查等侵入式治療，是醫院最常見的醫療操作，也是外源性感染之主要原因，因其會把細菌帶入膀胱，並同時有可能引起上行性細菌感染，進而造成細菌性膀胱炎，嚴重者往往會造成急性膀胱炎或腎臟炎等；如，一般最常見之細菌性膀胱炎，其發炎的所在係於膀胱的黏膜上呈現出紅、腫、血管充血等情形，而間質性膀胱炎其係於黏膜的下層與肌肉層之間產生發炎現象，因此，當膀胱炎發生時一般會導致膀胱不適和疼痛，並出現頻尿、尿液急迫有關的病症，而且當治療膀胱炎不當時，往往會因為膀胱產生嚴重的感染，而可能會使病患的腎臟失去功能，以後可能需要洗腎，甚至有死於敗血症的危險。而目前治療膀胱炎之療法主要有藥物治療法、抗菌膀胱灌洗術或滴注法給藥等膀胱炎治療法，其中，無論是利用滴注法給藥做為單一療法，或者將滴注法結合其他治療法之聯合療法，或者將上述三者結合之順序療法，其所使用之藥物，如二甲基亞礬、氧氯苯磺酸鈉(clorpactin)、肝素、透明質酸、阿霉素、硫酸軟骨素、碳酸氫鈉、硝酸銀、戊聚糖多硫酸鈉、色甘酸鈉、青黴素、呋喃西林、慶大黴素或弱蛋白銀等，多係以膀胱黏膜及間質組織層為治療膀胱炎之目標，藉此使疼痛、尿酸和尿急等膀胱炎之症狀可獲得緩解，而預防泌尿道細菌感染的技術有抗生素法預防、導尿管表面塗藥技術、含銀或鍍銀導尿管技術等，惟，在這些膀胱炎療法中或預防泌尿道細菌感染的技術，很少能夠在持續時間內產生緩解作用，或者進行長期治療與使用該預防技術，並且在治療期間同時會具有一些副作用。According to the common urinary system diseases, cystitis or urinary tract infections may occur. The urinary system may be caused by bacteria, chemical drugs, radiation, anticancer drugs or infections caused by exogenous bacteria, or may be caused by drugs. Causes the resistance to decrease, resulting in bacterial invasion, and it is particularly common in women or patients with catheters, and the simplest method of judging is whether or not cystitis occurs by the presence or absence of bacteriuria. The amount of bacteria in milliliters of urine is greater than 10 5 CFU, of which about 98% of the male genital tract in the distal part of the urethra is 98%, and 49% in the 5 cm; while the rate of bacterial colonization in women may be higher, therefore, when the urine When the amount of liquid bacteria is too high, cystitis or pyelonephritis is produced; and according to the statistics of nosocomial infection in Taiwan intensive care unit in 2007, urinary tract infection accounts for 37.5% of hospital infections, and whether it is a medical center or regional hospital, urinary tract The infection of the road is the highest in the hospital in the intensive care unit of Taiwan. Therefore, the urinary system diseases caused by bacterial infections in all age groups are still high in urinary tract infection. Ranked first. Invasive treatment, such as catheter insertion or cystoscopy, is the most common medical procedure in hospitals and the main cause of exogenous infections, as it can bring bacteria into the bladder and may also cause ascending bacteria. Infection, which causes bacterial cystitis, severe cases often lead to acute cystitis or nephritis; for example, the most common bacterial cystitis, the inflammation is located in the mucosa of the bladder showing redness, swelling, blood vessels In the case of congestion, interstitial cystitis is caused by inflammation between the lower layer of the mucous membrane and the muscle layer. Therefore, when cystitis occurs, bladder discomfort and pain are generally caused, and frequent urination and urinary urgency are associated. Illness, and when treating cystitis, it is often caused by a serious infection of the bladder, which may cause the kidneys of the patient to lose function. Later, it may be necessary to wash the kidneys and even die of sepsis. At present, the treatment of cystitis mainly includes the treatment of cystitis such as drug therapy, antibacterial bladder lavage or drip administration, wherein either the instillation method is used as a monotherapy or the drip method is used. Combination therapy with other treatments, or sequential therapy combining the above three drugs, such as dimethyl sulfoxide, clorpactin, heparin, hyaluronic acid, doxorubicin Chondroitin sulfate, sodium bicarbonate, silver nitrate, sodium pentosan polysulfate, sodium cromoglycate, penicillin, nitrofurazone, gentamicin or weak protein silver, etc., the treatment of cystitis with bladder mucosa and interstitial tissue layer The goal is to relieve the symptoms of cystitis such as pain, uric acid and urgency, and the techniques for preventing bacterial infections in the urinary tract are antibiotic prophylaxis, catheter surface coating techniques, silver-containing or silver-plated catheters. Techniques, etc., however, techniques for preventing or treating urinary tract bacterial infections in these cystitis therapies are rarely able to produce remission for a sustained period of time, or for long-term treatment and use of this prevention technique, and And it will have some side effects during treatment.
然，對於膀胱炎的治療，若單純依賴抗菌藥物治療感染，而該抗菌藥物其對膀胱黏膜及間質組織因無法立刻進行修補，而往往達不到預期效果；如果能對已被破壞的膀胱黏膜及間質組織進行有效的修補，同時能找出引起感染的原因並及時給予必要的處理，方可更有效地控制感染，防止反覆發作，並促使膀胱表面傷口癒合，使膀胱炎患者之病症得以舒緩，實有其必要性。However, for the treatment of cystitis, if it relies solely on antibacterial drugs to treat infection, and the antibacterial drug can not immediately repair the bladder mucosa and interstitial tissue, it often fails to achieve the desired effect; if it can be used for the damaged bladder The mucosa and interstitial tissues can be effectively repaired, and the cause of the infection can be found and the necessary treatment can be given in time to control the infection more effectively, prevent the repeated attacks, and promote the wound healing of the bladder surface, and the symptoms of cystitis patients. It is necessary to be soothed.
本發明係提供一種治療泌尿系統的醫藥組成物，其係將碳含量之重量百分比在60wt%以上之碳材料載於一含水載體，使兩者形成藥用上可接受之載有碳材料之含水載體，並使載有碳材料之含水載體其每單位劑量包含有介於0.1mg/ml至100mg/ml間之碳材料，且該碳材料之直徑係介於2nm至2mm之間，而該碳材料進一步更含有可選自由銀、鉑、鈀、金、鋅或銅其中之一或其組成之族群之之金屬顆粒，且該金屬顆粒之直徑係介於2nm至2mm之間。The present invention provides a pharmaceutical composition for treating a urinary system, wherein a carbon material having a carbon content of 60% by weight or more is contained in an aqueous carrier to form a pharmaceutically acceptable water-bearing material. a carrier, and the aqueous carrier carrying the carbon material comprises a carbon material between 0.1 mg/ml and 100 mg/ml per unit dose, and the diameter of the carbon material is between 2 nm and 2 mm, and the carbon The material further comprises metal particles optionally selected from the group consisting of silver, platinum, palladium, gold, zinc or copper or a group thereof, and the diameter of the metal particles is between 2 nm and 2 mm.
本發明所提供之一種治療泌尿系統的醫藥組成物，其所含之碳材料或者結合金屬顆粒之碳材料均可與動物體內之膀胱及其相關組織相接觸，用以治療與預防膀胱炎、急性膀胱炎，慢性膀胱炎、***、細菌性膀胱炎、產氣性膀胱炎、間質性膀胱炎、膀胱或尿道有傷口患者、尿道感染之患者，同時能有效地控制感染，防止膀胱炎反覆發作，並促使膀胱表面傷口癒合，使膀胱炎患者之病症得以舒緩。The invention provides a pharmaceutical composition for treating a urinary system, wherein the carbon material or the carbon material combined with the metal particles can be contacted with the bladder and related tissues in the animal for treating and preventing cystitis and acute Cystitis, chronic cystitis, hemorrhagic cystitis, bacterial cystitis, gastritis cystitis, interstitial cystitis, patients with wounds in the bladder or urethra, patients with urinary tract infections, can effectively control infection, prevent bladder The inflammation recurs and causes the wound on the surface of the bladder to heal, so that the symptoms of patients with cystitis can be relieved.
本發明一種治療泌尿系統的醫藥組成物之較佳實施例，該用於治療泌尿系統之醫藥組成物其主要係將碳含量之重量百分比在60wt%以上之碳材料載於一含水載體，使兩者形成藥用上可接受之載有碳材料之含水載體，而該碳材料係選自由碳纖維、活性碳纖維、活性碳、石墨、膨脹石墨、奈米碳管、奈米碳球、焦碳球或碳黑其中之一或其組成群組之碳材料，且該碳材料之直徑係介於20nm至2mm之間，而其結構及比表面積值(BET)係為20m2 /g~4000m2 /g之間，其中，本發明較佳實施例其碳材料係為活性碳纖維粉末或活性碳，其碳含量之重量百分比係在80wt%以上，且結構及比表面積值(BET)係為200m2 /g~3000m2 /g之間，同時，該含水載體係選自由緩衝液、抗生素藥劑和治療膀胱炎藥劑其中之一或其組合所組成之群族，且該載有碳材料之含水載體其每單位劑量係包含0.01mg/ml以上之碳材料，其中，本發明較佳實施例中該載有碳材料之含水載體其係為每單位劑量中含有0.1mg/ml至500mg/ml間之碳材料；另，本發明第二實施例其主要組成與所產生之功效係為較佳實施例相同，故不再贅述，其中，該碳材料進一步係結合一金屬顆粒，該金屬顆粒係選自由銀、鉑、鈀、金、鋅或銅其中之一或其組成之族群之小顆粒金屬，且該金屬顆粒之直徑係介於2nm至2mm之間，且該金屬顆粒係佔碳材料重量之重量百分比係為20wt%以下，本第二實施例其小顆粒金屬係佔碳材料重量之重量百分比係為5wt%以下，該小顆粒金屬與碳材料相結合後再載於含水載體而形成治療泌尿系統的醫藥組成物；另，該含水載體之抗生素藥劑係選自由Trimethoprim-sulfame-thoxazole(TMP-SMX)、Trimethoprim(TMP)、sulfame-thoxazole(SMX)、fluoroquinolones、Ciprofloxacin、Ofloxacin、Cephalexin與四環黴素之一或其組合之抗生素藥劑；而該含水載體之治療膀胱炎藥劑係選自由二甲基亞礬、氧氯苯磺酸納(Clorpactin)、肝素、透明質酸、阿霉素、硫酸軟骨素、碳酸氫鈉、硝酸銀、戊聚糖多硫酸鈉、色甘酸鈉、青黴素、呋喃西林、慶大黴素或弱蛋白銀之一或其組合之治療膀胱炎藥劑。A preferred embodiment of a pharmaceutical composition for treating a urinary system, wherein the pharmaceutical composition for treating a urinary system is mainly characterized in that a carbon material having a carbon content of 60% by weight or more is contained in an aqueous carrier, so that two Forming a pharmaceutically acceptable aqueous carrier carrying a carbon material selected from the group consisting of carbon fiber, activated carbon fiber, activated carbon, graphite, expanded graphite, carbon nanotubes, carbon spheres, coke spheres or One of carbon black or a carbon material thereof, and the diameter of the carbon material is between 20 nm and 2 mm, and the structure and specific surface area (BET) are 20 m 2 /g to 4000 m 2 /g. Between the preferred embodiments of the present invention, the carbon material is activated carbon fiber powder or activated carbon, the carbon content thereof is 80% by weight or more, and the structure and specific surface area value (BET) is 200 m 2 /g. Between ~3000 m 2 /g, at the same time, the aqueous carrier is selected from the group consisting of a buffer, an antibiotic agent, and a cystitis agent, or a combination thereof, and the aqueous carrier carrying the carbon material per unit Dosage system contains 0.01mg/ml or more A carbon material, wherein the aqueous carrier carrying the carbon material in the preferred embodiment of the present invention is a carbon material containing 0.1 mg/ml to 500 mg/ml per unit dose; and the second embodiment of the present invention The main composition and the resulting effect are the same as the preferred embodiment, and therefore will not be described again, wherein the carbon material is further combined with a metal particle selected from the group consisting of silver, platinum, palladium, gold, zinc or copper. a small particle metal of one or a group thereof, and the diameter of the metal particles is between 2 nm and 2 mm, and the metal particles are 20% by weight or less by weight of the carbon material, the second embodiment The small particle metal is 5% by weight or less based on the weight of the carbon material, and the small particle metal is combined with the carbon material and then loaded on the aqueous carrier to form a pharmaceutical composition for treating the urinary system; The agent is selected from the group consisting of Trimethoprim-sulfame-thoxazole (TMP-SMX), Trimethoprim (TMP), sulfame-thoxazole (SMX), fluoroquinolones, Ciprofloxacin, Ofloxacin, Cephalexin and tetracycline or a group thereof. An antibiotic agent; and the aqueous carrier for treating cystitis is selected from the group consisting of dimethyl hydrazine, clopactin, heparin, hyaluronic acid, doxorubicin, chondroitin sulfate, sodium hydrogencarbonate, A cystitis agent for treating one or a combination of silver nitrate, pentosan sodium polysulfate, sodium cromoglycate, penicillin, nitrofurazone, gentamicin or weak protein silver.
藉此，使該醫藥組成物之碳材料或者結合金屬顆粒之碳材料均可與動物體內之膀胱及其相關組織相接觸，用以治療與預防膀胱炎、急性膀胱炎，慢性膀胱炎、***、細菌性膀胱炎、產氣性膀胱炎、間質性膀胱炎、膀胱或尿道有傷口患者及尿道感染之患者，同時能有效地控制感染，防止膀胱炎反覆發作，並促使膀胱表面傷口癒合，使膀胱炎患者之病症得以舒緩。Thereby, the carbon material of the medical composition or the carbon material combined with the metal particles can be contacted with the bladder and related tissues in the animal for treating and preventing cystitis, acute cystitis, chronic cystitis, hemorrhagic Cystitis, bacterial cystitis, gas-producing cystitis, interstitial cystitis, patients with wounds in the bladder or urethra, and patients with urinary tract infections, can effectively control infection, prevent repeated attacks of cystitis, and promote wounds on the bladder surface Healing, so that the symptoms of patients with cystitis can be relieved.
為供進一步瞭解本發明構造特徵、運用技術手段及所預期達成之功效，茲將本發明使用方式加以敘述，相信當可由此而對本發明有更深入且具體之瞭解，如下所述：請參閱第一圖至第五圖所示，該醫藥組成物之碳材料係為活性碳纖維，其進一步係為購自由台碳科技股份有限公司(TAIWAN CARBON TECHNOLOGY CO.，LTD)所生產與販售之活性碳纖維，並經研磨至顆粒為50μm到100μm，其碳材料的結構及比表面積值為200m2 /g~2000m2 /g，而本發明較佳實施例之含水載體係為緩衝液，而該緩衝液進一步係為無菌水，其係將碳材料加於緩衝液中充份攪拌而成為載有碳材料之含水載體，且載有碳材料之含水載體之每單位劑量係含有0.2mg/ml之碳材料，並選用三隻雌性Sprague-Dawley大鼠，其重量約為290g，再分別分組為：For a further understanding of the structural features of the present invention, the application of the technical means, and the intended effect, the present invention will be described. It is believed that the present invention may be further understood and understood as follows: As shown in the first to fifth figures, the carbon material of the pharmaceutical composition is activated carbon fiber, which is further produced as an activated carbon fiber produced and sold by TAIWAN CARBON TECHNOLOGY CO., LTD. And grinding to a particle size of 50 μm to 100 μm, the carbon material has a structure and a specific surface area value of 200 m 2 /g to 2000 m 2 /g, and the aqueous carrier of the preferred embodiment of the present invention is a buffer, and the buffer Further, it is a sterile water which is added to a buffer to be fully stirred to form an aqueous carrier carrying a carbon material, and the aqueous carrier carrying the carbon material contains 0.2 mg/ml of carbon material per unit dose. Three female Sprague-Dawley rats weighing approximately 290 g were selected and grouped into:
(1)、M1-1(Normal)：正常的大鼠，未注射誘導發炎劑，且未誘導膀胱發炎。(1), M1-1 (Normal): Normal rats, no injection of an induced inflammatory agent, and no induction of bladder inflammation.
(2)、M1-2(LPS)：注射誘導發炎劑，誘導膀胱發炎。(2), M1-2 (LPS): injection induces an inflammatory agent to induce inflammation of the bladder.
(3)、M1-3(LPS-ACF)：注射誘導發炎劑，誘導膀胱發炎，再將碳材料之含水載體注射入膀胱內治療。(3), M1-3 (LPS-ACF): injection induces an inflammatory agent, induces inflammation of the bladder, and then injects an aqueous carrier of carbon material into the bladder for treatment.
並於開始實驗前該等大鼠先以氨基鉀酸酯(urethane)進行麻醉，確認大鼠已經麻醉後將其以膠帶固定於軟板上，再以聚乙烯管(polyethylene tube，PE-50)進行尿道插管，待上述程序完成後再進行下列步驟：先對M1-2(LPS)組及M1-3(LPS-ACF)組之兩隻大鼠分別從尿道注射硫酸魚精蛋白(Protamine sulfate，PS)入該等大鼠之膀胱，並先導致M1-2(LPS)組及M1-3(LPS-ACF)組之兩隻大鼠其膀胱黏膜受傷，再注射誘導發炎劑，本發明較佳實施例所注射之誘導發炎劑係為通稱內毒素的酯多聚醣體(Lipopolysaccharides，LPS)來達到誘導膀胱受傷發炎的效果，並造成該等大鼠膀胱產生發炎現象產生，在注射硫酸魚精蛋白後45分鐘，再注射生理食鹽水(normal saline)清洗膀胱，控制傷害範圍，防止硫酸魚精蛋白進一步去傷害到膀胱間質層細胞。Before the start of the experiment, the rats were anesthetized with urethane, and it was confirmed that the rats were anesthetized and then taped to a soft plate, and then polyethylene tube (PE-50). The urethral cannula was performed. After the above procedure was completed, the following steps were performed: firstly, two rats in the M1-2 (LPS) group and the M1-3 (LPS-ACF) group were injected with protamine sulfate from the urethra respectively. , PS) into the bladder of these rats, and first caused two bladders in the M1-2 (LPS) group and the M1-3 (LPS-ACF) group to injure the bladder mucosa, and then inject the induced inflammatory agent, the present invention The induced inflammatory agent injected in the preferred embodiment is an endotoxin-like lipopolysaccharide (LPS) to achieve the effect of inducing inflammation of the bladder injury, and causes inflammation of the bladder of the rat. 45 minutes after protamine, the bladder was washed with normal saline to control the extent of damage and prevent protamine sulfate from further injuring the bladder interstitial cells.
於清洗膀胱後，再注射誘導發炎劑即內毒素750 E.U.並再誘導該等大鼠其膀胱產生發炎現象，同時每半個小時注射一次該誘導發炎劑合計兩次，之後再以生理食鹽水(normal saline)清洗膀胱，經過一小時，三隻大鼠分別收集第一次尿液。After washing the bladder, the injection of the inducing agent, endotoxin 750 EU, is induced and the inflammation of the bladder is induced in the rats. At the same time, the induced inflammatory agent is injected twice every half hour, and then the physiological saline solution is used. Normal saline) The bladder was cleaned and, after one hour, three rats collected the first urine.
接著對M1-3(LPS-ACF)組之大鼠注射該醫藥組成物，而該醫藥組成物其碳材料之含水載體加於緩衝液後，其每單位劑量濃度係為4mg/20ml，而對M1-2(LPS)組之大鼠則僅注射生理食鹽水，且每半個小時注射一次，共需注射四次，再經過一小時，三隻大鼠分別收集第二次尿液，總共經過24小時後，再收集此三隻大鼠的膀胱，以供秤重及製作此三組大鼠其膀胱H & E染色病理切片。Then, the medicinal composition was injected into the rats of the M1-3 (LPS-ACF) group, and the aqueous carrier of the medical composition of the medical composition was added to the buffer, and the concentration per unit dose was 4 mg/20 ml, and In the M1-2 (LPS) group, only normal saline was injected, and every half hour was injected once. A total of four injections were required. After one hour, the three rats collected the second urine separately. After 24 hours, the bladders of the three rats were collected for weighing and the pathological sections of the bladder of the three groups were stained with H & E staining.
請再參閱第一圖所示，分析第一次收集尿液中，該M1-1(Normal)組係為對照組所以不用採集，而M1-2(LPS)組之大鼠其誘導發炎劑高達9.6EU/ml，該M1-3(LPS-ACF)組的誘導發炎劑即高達36.0EU/ml；而經三小時後並再分析第二次所收集尿液中，該M1-1(Normal)組係為對照組其誘導發炎劑係為1.0EU/ml，該M1-2(LPS)組其誘導發炎劑則降至1.8EU/ml，該M1-3(LPS-ACF)組係經注射具有該載有碳材料之含水載體之醫藥組成物後，其誘導發炎劑的含量則降到1.0EU/ml，經分別比較M1-1(Normal)組、M1-2(LPS)組與M1-3(LPS-ACF)組之三隻大鼠其誘導發炎劑測試的結果後可知，由M1-3(LPS-ACF)組可知，M1-2(LPS)組在注射誘導發炎劑後，第一次尿液中其誘導發炎劑含量在9.6EU/ml，而誘導發炎劑經大鼠體內自然代謝後，於三小時第二次尿液中其誘導發炎劑仍殘存1.8EU/ml於大鼠體內；而M1-3(LPS-ACF)組之大鼠在注射誘導發炎劑誘導膀胱發炎，在第一次尿液中其誘導發炎劑濃度高達36.0EU/ml，但經注入該載有碳材料之含水載體之醫藥組成物後，在第二次尿液中其誘導發炎劑含量已降至1.0EU/ml，係誘導發炎劑含量係與M1-1(Normal)對照組相同，這表示載有碳材料之含水載體之醫藥組物係使大鼠已發炎的膀胱產生治療效果；請再參閱第一圖所示，由三隻大鼠所量的膀胱重量亦可以看出注射該載有碳材料之含水載體之醫藥組成物其治療效果；該M1-2(LPS)組之大鼠於其膀胱重量為177.3mg；而M1-3(LPS-ACF)組之大鼠於注射誘導發炎劑誘導膀胱發炎後，並經注射該載有含碳材料之含水載體之醫藥組成物進行治療，該M1-3(LPS-ACF)組之大鼠於冶療後之膀胱重量降至134.8mg，這表示注射該載有碳材料之含水載體之醫藥組成物已產生治療因膀胱炎所造成之水腫效果。Please refer to the first figure, in the first collection of urine, the M1-1 (Normal) group is the control group, so there is no collection, and the M1-2 (LPS) group of rats induces the inflammatory agent up to 9.6 EU/ml, the induced inflammatory agent of the M1-3 (LPS-ACF) group was as high as 36.0 EU/ml; and after three hours and then analyzed for the second collected urine, the M1-1 (Normal) The group was the control group, the induced inflammatory agent was 1.0 EU/ml, and the M1-2 (LPS) group was induced to reduce the inflammatory agent to 1.8 EU/ml. The M1-3 (LPS-ACF) group was injected with After the pharmaceutical composition containing the aqueous carrier of the carbon material, the content of the induced inflammatory agent was reduced to 1.0 EU/ml, and the M1-1 (Normal) group, the M1-2 (LPS) group and the M1-3 were compared, respectively. After the results of the inflammatory agent test were induced in the three rats of the (LPS-ACF) group, it was found from the M1-3 (LPS-ACF) group that the M1-2 (LPS) group was injected for the first time after the induction of the inflammatory agent. In the urine, the induced inflammatory agent content is 9.6 EU/ml, and after the induced inflammatory agent is naturally metabolized in the rat, the induced inflammatory agent remains in the second urine for three hours, and 1.8 EU/ml remains in the rat; Rats in the M1-3 (LPS-ACF) group were induced to induce inflammatory agents by injection. Cystitis, which induces an inflammatory agent concentration of up to 36.0 EU/ml in the first urine, but after injecting the pharmaceutical composition of the aqueous carrier carrying the carbon material, it induces an inflammatory agent content in the second urine. It has been reduced to 1.0 EU/ml, and the induced inflammatory agent content is the same as that of the M1-1 (Normal) control group, which means that the medical group containing the aqueous carrier of the carbon material has a therapeutic effect on the inflamed bladder of the rat; Please refer to the first figure. The weight of the bladder from three rats can also be seen as the therapeutic effect of the pharmaceutical composition injected with the aqueous carrier carrying the carbon material; the M1-2 (LPS) group is large. The rat has a bladder weight of 177.3 mg; and the M1-3 (LPS-ACF) group is treated with a pharmaceutical composition containing an aqueous carrier containing a carbonaceous material after injecting an inflammatory agent to induce inflammation of the bladder. The weight of the bladder of the M1-3 (LPS-ACF) group decreased to 134.8 mg after the treatment, which means that the pharmaceutical composition for injecting the aqueous carrier carrying the carbon material has been treated to cause cystitis. Edema effect.
為了更進一步了解大鼠膀胱內部情形，請參閱第二圖所示，其係為M1-1(Normal)組之大鼠其正常之膀胱H & E染色切片，由第二圖上可以清楚看到在正常情況下，其膀胱表面看到很平滑的膀胱黏膜上皮細胞；請參閱第三圖所示，其係為M1-2(LPS)組之大鼠經誘導發炎劑誘導發炎後其膀胱之H & E染色切片，並可以看到M1-2(LPS)組之大鼠因發炎現象導致白血球聚集在黏膜下方的膀胱間質層，同時參閱第四圖所示，該M1-2(LPS)組之大鼠其內部組織可觀察到很嚴重的內出血現象，請參閱第五圖所示，其係為M1-3(LPS-ACF)組之大鼠經誘導發炎劑即內毒素誘導發炎，並經注射該載有碳材料之含水載體之醫藥組成物之治療，其膀胱之H & E染色切片經比較該M1-3(LPS-ACF)的膀胱黏膜組織，與第二圖該M1-1(Normal)組正常大鼠之膀胱黏膜組織可以發現兩者係很類似，該M1-3(LPS-ACF)組大鼠之並沒有發現有白血球聚集、水腫、內出血等膀胱嚴重發炎之現象，因此，這表示該載有碳材料之含水載體之醫藥組成物係使大鼠已發炎的膀胱產生治療效果。In order to further understand the internal conditions of the rat bladder, please refer to the second figure, which is a normal bladder H & E stained section of the M1-1 (Normal) group, which can be clearly seen from the second figure. Under normal conditions, the bladder surface of the bladder surface is very smooth; see the third figure, which is the M2 (LPS) group of rats induced by inflammation of the inflammatory agent after the bladder H & E stained sections, and it can be seen that the M1-2 (LPS) group caused white blood cells to accumulate in the interstitial layer of the bladder under the mucosa due to inflammation, and as shown in the fourth figure, the M1-2 (LPS) group In the rat's internal tissues, very serious internal bleeding was observed. Please refer to the fifth figure. The rats in the M1-3 (LPS-ACF) group were induced to be inflamed by the induced inflammatory agent, endotoxin. The treatment of the pharmaceutical composition of the aqueous carrier carrying the carbon material, the H & E stained section of the bladder is compared with the bladder mucosa tissue of the M1-3 (LPS-ACF), and the M1-1 (Normal) of the second figure The bladder mucosa of normal rats can be found to be very similar, and the M1-3 (LPS-ACF) group did not. There are serious inflammation of the bladder leukocyte aggregation, edema, bleeding, etc. Thus, this means that the composition contains an aqueous-based pharmaceutical carrier of the carbon material bladder inflammation The rats have a therapeutic effect.
請參閱第六圖至第九圖所示，其主要實施方式係與本發明較佳實施例相同，故不再贅述，其中，該實施方式主要係量測大鼠血清中之前降鈣素(Procalcitonin，PCT)含量，而血清中之前降鈣素含量的濃度測定主要係用以判斷嚴重細菌性感染與全身發炎反應之主要指標，因此，當前降鈣素濃度上昇時，係主要系表示其膀胱發炎現象為細菌性的感染、敗血症休克或其它嚴重型全身性細菌感染而造成膀胱發炎。Please refer to the sixth to ninth embodiments, the main embodiments of which are the same as the preferred embodiment of the present invention, and therefore will not be described again. The embodiment mainly measures the calcitonin in the serum of the rat (Procalcitonin). , PCT) content, and the concentration of previous calcitonin in serum is mainly used to determine the main indicators of serious bacterial infection and systemic inflammatory response. Therefore, when the current calcitonin concentration rises, the main line indicates that the bladder is inflamed. The phenomenon is bacterial infection, septic shock or other serious systemic bacterial infections that cause bladder inflammation.
請再參閱第六圖所示，M2-1(Normal)組係為對照之正常大鼠，其前降鈣素濃度為0.021ng/ml；M2-2(LPS)組係為經誘導發炎劑而誘導發炎之大鼠，其前降鈣素濃度增加至0.036ng/ml；而M2-3(LPS-ACF)組係為經誘導發炎劑誘導發炎，並經注射治療後之大鼠，其前降鈣素濃度係為0.02ng/ml，經比較可發現M2-3(LPS-ACF)組大鼠與M2-1(Normal)組大鼠之前降鈣素濃度相當，並同時比較M2-2(LPS)組大鼠之膀胱重量為177.6mg，與M2-3(LPS-ACF)組大鼠之膀胱重量於治療後已降至138.1mg可發現，該載有碳材料之含水載體之醫藥組成物對膀胱發炎確實具有療效。Please refer to the sixth figure. The M2-1 (Normal) group is a control normal rat with a procalcitonin concentration of 0.021 ng/ml; the M2-2 (LPS) group is an induced inflammatory agent. In rats with induced inflammation, the procalcitonin concentration increased to 0.036 ng/ml; while the M2-3 (LPS-ACF) group was induced by an induced inflammatory agent, and the rats were injected after treatment. The calcium concentration was 0.02 ng/ml. It was found that the M2-3 (LPS-ACF) group and the M2-1 (Normal) group had the same calcitonin concentration and compared M2-2 (LPS). The bladder weight of the rats in the group was 177.6 mg, and the bladder weight of the rats in the M2-3 (LPS-ACF) group was reduced to 138.1 mg after the treatment, and the pharmaceutical composition of the aqueous carrier carrying the carbon material was found. Inflammation of the bladder does have a therapeutic effect.
請再參閱第七圖至第九圖所示，其係為該等不同組別之大鼠其膀胱之H & E染色病理組織切片，請先參閱第七圖所示該M2-1(Normal)組其大鼠的膀胱組織切片可以看到很平滑的膀胱黏膜，而第八圖所示該M2-2(LPS)組其大鼠的膀胱組織切片由圖中左側可以看到很嚴重的水腫現象；而第九圖所示該M2-3(LPS-ACF)組其大鼠的膀胱組織切片可以看到呈現平滑的膀胱黏膜表面，同時並沒有發現白血球聚集、水腫及內出血等膀胱嚴重發炎現象，因此，表示該載有碳材料之含水載體之醫藥組成物係使大鼠已發炎的膀胱產生治療效果。Please refer to the seventh to ninth figures, which are the H & E stained pathological sections of the bladder of the different groups of rats. Please refer to the M2-1 (Normal) shown in the seventh figure. In the bladder tissue section of the rats, a very smooth bladder mucosa was observed, and in the M2-2 (LPS) group, the bladder tissue sections of the rats in the eighth figure showed severe edema from the left side of the figure. In the ninth figure, the bladder tissue of the M2-3 (LPS-ACF) group showed smooth surface of the bladder mucosa, and no serious inflammation of the bladder such as white blood cell aggregation, edema and internal bleeding was observed. Therefore, the pharmaceutical composition indicating the aqueous carrier carrying the carbon material produces a therapeutic effect on the inflamed bladder of the rat.
請參閱第十圖至第十二圖所示，係為該等不同組別之大鼠其膀胱之H & E染色病理組織切片，其主要實施方式係與本發明較佳實施例相同，故不再贅述，其中，M3-3(LPS-ACF)組所注射之用以治療膀胱炎之醫藥組成物係為本發明之第二實施例，而其主要係將金屬顆粒與該碳材料相結合後再載於含水載體而形成用於治療膀胱炎之醫藥組成物，而本發明第二實施例所選用之金屬顆粒係為奈米級金屬銀顆粒，請先參閱第十圖所示係為M3-1(Normal)組之正常大鼠其膀胱H & E染色切片，由第十圖可以看到係無發炎、無水腫與無內出血之病狀，而參閱第十一圖所示可以看到M3-2(LPS)組經誘導發炎劑誘導膀胱發炎後，其圖中可以見到明顯的白血球聚集、水腫及內出血等膀胱嚴重發炎現象，請再參閱第十二圖所示可以看到M4-3(LPS-ACF)組之大鼠，其先經誘導發炎劑誘導發炎，再藉由注入含有銀之金屬顆粒的碳材料加以治療後，由第十二圖可以發現並沒有白血球聚集、水腫與內出血等膀胱嚴重發炎現象，因此，該碳材料與含銀之金屬顆粒相結合所形成之醫藥組成物具有殺菌及降低膀胱炎之症狀的效果。Referring to the tenth to twelfth figures, the H & E stained pathological tissue sections of the bladder of the different groups of rats are the same as the preferred embodiment of the present invention, so Further, the pharmaceutical composition for treating cystitis injected by the M3-3 (LPS-ACF) group is the second embodiment of the present invention, and the main method is to combine the metal particles with the carbon material. The medicinal composition for treating cystitis is formed on the aqueous carrier, and the metal particles selected in the second embodiment of the present invention are nano-sized metallic silver particles. Please refer to the tenth figure for the M3- The normal rats of the 1 (Normal) group were stained with H & E staining of the bladder. From the tenth figure, it can be seen that there is no inflammation, no edema and no internal bleeding. See Figure 11 for M3- 2 (LPS) group induced inflammation of the bladder induced by the inflammatory agent, in the figure can be seen in the white blood cell aggregation, edema and internal bleeding and other serious bladder inflammation, please see the twelfth figure can see M4-3 ( Rats in the LPS-ACF group, which are induced to induce inflammation by inducing inflammatory agents, and then by injection After the treatment of the carbon material containing the metal particles of silver, it can be found from the twelfth figure that there is no serious inflammation of the bladder such as white blood cell aggregation, edema and internal bleeding. Therefore, the medicine formed by combining the carbon material with the metal particles containing silver The composition has the effect of sterilizing and reducing the symptoms of cystitis.
藉由以上說明，可將本發明之優點與可達成功效整理如下：By the above description, the advantages and achievable effects of the present invention can be summarized as follows:
1、本發明之治療泌尿系統的醫藥組成物，該碳材料載於一含水載體，使兩者形成藥用上可接收之載有碳材料之含水載體，並可為膀胱黏膜所接受，進而舒緩膀胱炎所產生之現象，同時並具有長時效之治療效果。A pharmaceutical composition for treating a urinary system according to the present invention, the carbon material being contained in an aqueous carrier to form a pharmaceutically acceptable aqueous carrier carrying a carbon material, which is acceptable for the bladder mucosa and thereby soothes The phenomenon caused by cystitis, and has a long-lasting therapeutic effect.
2、本發明之治療泌尿系統的醫藥組成物，其中，載於一含水載體，使兩者形成藥用上可接收之載有碳材料之含水載體，其進一步係可對膀胱黏膜進行修補產生進一步治療效果。2. A pharmaceutical composition for treating a urinary system according to the present invention, which comprises an aqueous carrier which forms a pharmaceutically acceptable aqueous carrier carrying a carbonaceous material, which further repairs the bladder mucosa to further produce treatment effect.
3、本發明之治療泌尿系統的醫藥組成物，該碳材料所結合之金屬顆粒係選自由銀、鉑、鈀、金、鋅或銅其中之一或其組成之族群之金屬顆粒，且該金屬顆粒之直徑係介於2nm至2mm之間，藉由碳材料結合奈米級之金屬顆粒，而加強其殺菌及降低膀胱炎之症狀之效果。3. The pharmaceutical composition for treating a urinary system according to the present invention, wherein the metal particles combined with the metal material are selected from the group consisting of metal particles of one or a group consisting of silver, platinum, palladium, gold, zinc or copper, and the metal The diameter of the particles is between 2 nm and 2 mm, and the carbon material is combined with the metal particles of the nano-grade to enhance the sterilization and reduce the symptoms of cystitis.
4、本發明之治療泌尿系統的醫藥組成物，其所含之碳材料具較高之結構及比表面積值，以及良好的生物相容性，可以主動吸附細菌，使膀胱內致病細菌量快速降低到105 CFU以下，並吸附細菌的外毒素與內毒素，與有害物質。並隨著尿液排出體外，而達到預防的效果。4. The pharmaceutical composition for treating the urinary system of the present invention, which comprises a carbon material having a high structure and specific surface area value, and good biocompatibility, can actively adsorb bacteria, and rapidly cause pathogenic bacteria in the bladder. Reduce to below 10 5 CFU and absorb bacterial exotoxin and endotoxin, with harmful substances. And as the urine is excreted, the preventive effect is achieved.
綜上所述，本發明在同類產品中實有其極佳之進步實用性，同時遍查國內外關於此類結構之技術資料，文獻中亦未發現有相同的構造存在在先，是以，本發明實已具備發明專利要件，爰依法提出申請。In summary, the present invention has excellent advancement and practicability in similar products, and at the same time, the technical materials of such structures are frequently investigated at home and abroad, and the same structure is not found in the literature. The invention already has the invention patent requirements, and the application is filed according to law.
惟，以上所述者，僅係本發明之一較佳可行實施例而已，故舉凡應用本發明說明書及申請專利範圍所為之等效結構變化，理應包含在本發明之專利範圍內。However, the above-mentioned ones are merely preferred embodiments of the present invention, and the equivalent structural changes of the present invention and the scope of the claims are intended to be included in the scope of the present invention.
《習知》"Knowledge"
《本發明》"this invention"
第一圖係為本發明較佳實施例其每一組大鼠尿液中誘導發炎劑含量測試與膀胱重量比較圖。The first figure is a comparison of the induced inflammatory agent content test and the bladder weight in the urine of each group of rats according to a preferred embodiment of the present invention.
第二圖係為本發明較佳實施例其M1-1(Normal)組之正常大鼠的膀胱H & E染色切片圖，內有血管(Blood vessel，BV)、構成黏膜的上皮細胞(Epithelium，Ep)、肌肉組織(Muscle，M)、結締組織(Connective tissue，CT)、以及間質層(Lamina propria，Lp)。The second figure is a histogram of bladder H & E staining of a normal rat of the M1-1 (Normal) group according to a preferred embodiment of the present invention, which has a blood vessel (BV) and an epithelial cell (Epithelium) which constitutes a mucosa. Ep), muscle tissue (Muscle, M), connective tissue (CT), and interstitial layer (Lamina propria, Lp).
第三圖係為本發明較佳實施例其M1-2(LPS)組之經大鼠誘導發炎劑誘導發炎後其膀胱H & E染色切片圖，並顯示已發炎之膀胱表面，已出現白血球(White blood cells，WBC)聚集、水腫(Edema)與出血(Bleed)現象。The third panel is a histogram of the bladder H&E staining of the M1-2 (LPS) group induced by the rat-induced inflammatory agent according to a preferred embodiment of the present invention, and shows that the inflamed bladder surface has appeared white blood cells ( White blood cells, WBC), edema (Edema) and bleeding (Bleed) phenomenon.
第四圖係為第三圖其M1-2(LPS)組膀胱黏膜下方組織之H & E染色切片圖，並顯示出現嚴重的內出血現象。The fourth panel is the H & E stained section of the tissue under the bladder mucosa of the M1-2 (LPS) group in the third panel, and shows severe internal bleeding.
第五圖係為本發明較佳實施例其M1-3(LSP-ACF)組之大鼠經誘導發炎劑誘導膀胱發炎，再注入載有碳材料之含水載體之醫藥組成物治療後其膀胱H & E染色切片圖。The fifth figure is a preferred embodiment of the present invention, wherein the M1-3 (LSP-ACF) group of rats induces inflammation of the bladder by inducing an inflammatory agent, and then injects a pharmaceutical composition containing an aqueous carrier containing a carbon material to treat the bladder H. & E stained slice.
第六圖為本發明較佳實施例其每一組大鼠血清中前降鈣素(PCT)的濃度及膀胱重量比較圖。Figure 6 is a graph comparing the concentration of procalcitonin (PCT) and bladder weight in serum of each group of rats in accordance with a preferred embodiment of the present invention.
第七圖係為本發明較佳實施例其M2-1(Normal)組之正常大鼠其膀胱H & E染色切片圖。The seventh panel is a histogram of the bladder H&E staining of the normal rats of the M2-1 (Normal) group according to a preferred embodiment of the present invention.
第八圖係為本發明較佳實施例其M2-2(LPS)組經誘導發炎劑誘導膀胱發炎後其已發炎之膀胱H & E染色切片圖，其圖左邊可以發現很嚴重的水腫現象。The eighth figure is a H&E stained slice of the inflamed bladder of the M2-2 (LPS) group induced by the inflammatory agent after induction of the inflammatory agent according to a preferred embodiment of the present invention, and a severe edema phenomenon can be found on the left side of the figure.
第九圖為本發明較佳實施例其M2-3(LPS-ACF)組經誘導發炎劑誘導膀胱發炎後，再注入載有碳材料之含水載體之醫藥組成物治療後，其膀胱H & E染色切片圖。Figure 9 is a view showing a preferred embodiment of the present invention in which the M2-3 (LPS-ACF) group is treated with a medicinal composition containing an aqueous carrier carrying a carbon material after induction of an inflammatory agent to induce inflammation of the bladder, and the bladder H & E Stained slice diagram.
第十圖為本發明第二實施例M3-1(Normal)組之正常大鼠，其膀胱H & E染色切片圖。Fig. 10 is a diagram showing the H & E staining of the bladder of a normal rat of the M3-1 (Normal) group according to the second embodiment of the present invention.
第十一圖為本發明第二實施例M3-2(LPS)組經誘導發炎劑誘導膀胱發炎後，其膀胱H & E染色切片圖，在圖左側可以看到白血球聚集、內出血。The eleventh figure is a second section of the present invention, in which the M3-2 (LPS) group induces inflammation of the bladder after induction of an inflammatory agent, and the histogram of the bladder H & E staining, and white blood cell aggregation and internal bleeding can be seen on the left side of the figure.
第十二圖為本發明第二實施例M4-3(LPS-ACF)組經誘導發炎劑誘導膀胱發炎，再注入載有碳材料之含水載體之醫藥組成物治療後，其膀胱H & E染色切片圖。Figure 12 is a second embodiment of the present invention, in which the M4-3 (LPS-ACF) group is induced by an inflammatory agent to induce inflammation of the bladder, and then injected with a pharmaceutical composition containing an aqueous carrier containing a carbon material, the bladder H & E staining is performed. Slice graph.
Claims (14)
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| TW099108401A TWI474818B (en) | 2010-03-22 | 2010-03-22 | Treatment of urinary system of medical composition |
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| 張薇馥，銀/活性碳複合材料備製與過濾消毒之研究，逢甲大學環境工程與科學學系碩士論文，2009年3月9日 洪銘謙，活性碳纖維布載奈米銀技術探討，逢甲大學材料科學所碩士論文，2008年11月28日 * |
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