本文選題：氨甲環(huán)酸緩釋片 + 反相高效液相色譜法　； 參考：《湖南師范大學》2014年碩士論文

【摘要】：目的：月經過多嚴重影響患者健康及正常生活,可致缺鐵性貧血和生活質量下降,常見治療方法有手術和藥物治療。氨甲環(huán)酸是一種抗纖維蛋白溶解劑,臨床上已經證明其能有效治療月經過多。本課題采用親水性骨架緩釋材料羥丙甲纖維素,研制開發(fā)出一種高效、低毒、穩(wěn)定、依從性好的治療月經過多的3.1類新藥氨甲環(huán)酸緩釋片,研究與完善其處方工藝、質量標準、穩(wěn)定性等臨床前工作,整理與總結臨床前申報所需的全部試驗資料和文獻資料,提出新藥和醫(yī)院新制劑臨床前注冊申請,獲得新藥和醫(yī)院新制劑臨床批件,填補國內空缺,降低醫(yī)療費用,方便臨床應用,有望成為治療月經過多的首選藥物,社會與經濟意義重大。 方法：根據已有的文獻資料的基礎上,本課題制訂氨甲環(huán)酸緩釋片的制備和工藝,并對其進行優(yōu)化。采用反相高相液相色譜法。色譜柱Diamonsil C18；流動相0.23%十二烷基硫酸鈉溶液-甲醇(60：40,V/V)；檢測波長220nm；流速0.8mLmin-1溫30℃；進樣量20μL。確定色譜條件并對其進行方法學驗證,確定所建立方法的可行性與可靠性。 1制劑處方工藝：進行處方前研究,以體外釋放度為主要考察指標,從處方因素和工藝因素等方面詳細考察各種因素對藥物釋放行為的影響,根據研究結果確定其最佳處方和工藝。 2質量研究與標準制定：對藥品的性狀、鑒別、檢查、含量測定等進行研究,建立釋放度、微生物限度、有關物質和含量測定等的方法學,制定完善、可行、可控的質量標準。 3制劑穩(wěn)定性研究：對氨甲環(huán)酸緩釋片進行穩(wěn)定性影響因素試驗、加速試驗、長期試驗,以性狀、釋放度、有關物質、含量、微生物限度等為重點檢查項目,考察溫度、濕度、光照對其質量的影響,以便確定其有效期。 結論：1選擇HPMC為親水凝膠緩釋骨架,篩選出最佳處方：氨甲環(huán)酸650mg；微晶纖維素28mg；微粉硅膠2g；預交化淀粉31mg；羥丙甲纖維素(K4)155g；聚維酮(K30)53mg；硬脂酸20mg；硬脂酸鎂11mg。采用濕法制粒壓片,硬度18～20kg,片重為950mg。 2采用《中國藥典》2010年版附錄XD第二法,以水、0.1mol L-1鹽酸、pH4.5醋酸鹽緩沖液和pH6.8磷酸鹽緩沖液為釋放介質,體積 900mL,采用RP-HPLC法對氨甲環(huán)酸緩釋片在不同釋放介質中的釋放度研究。初步確定本品15～30min釋放40～50%,45～90min釋放90%,120～150min釋放98～100%。證明氨甲環(huán)酸緩釋片可在規(guī)定時間內釋放量達到要求。 3制劑中輔料不影響氨甲環(huán)酸緩釋片的含量測定。氨甲環(huán)酸緩釋片在0.5007～4.0056mg mL-1范圍內峰面積與濃度呈良好的線性關系(r=0.9999)；檢測限和定量限分別為1.024、3.413gg；平均回收率均在98～102%(RSD%≤2%,n=9)。 4穩(wěn)定性試驗結果表明：本品影響因素試驗10d、加速試驗6個月、長期試驗9個月的各項考察指標與0d比較均無明顯變化,均在合格范圍內,其穩(wěn)定性良好,有效期暫定2年。 5經檢驗自制氨甲環(huán)酸緩釋片的各項指標與進口氨甲環(huán)酸緩釋片相近。 本課題通過建立反相高效液相色譜法測定,對氨甲環(huán)酸緩釋片進行釋放度考察,并對其建立質量標準,結果表明該法準確、簡便、快速,可用來對氨甲環(huán)酸緩釋片進行質量控制。
[Abstract]:Objective: menorrhagia seriously affects the healthy and normal life of the patients, which can lead to iron deficiency anemia and the decline of the quality of life. The common treatment methods are surgical and drug treatment. Methicinic acid is an anti fibrinolytic agent. It has been proved to be effective in the treatment of menorrhagia. It has developed and developed a highly effective, low toxic, stable and compliant 3.1 new drug for the treatment of menorrhagia, methicate sustained release tablets, study and improve the pre clinical work of the prescription, quality standards, stability and so on, to sort out all the test data and documents needed for the pre clinical declaration, and put forward new drugs and hospital new preparations. It is expected to become the first choice for the treatment of menorrhagia, and it is of great social and economic significance to apply for new drugs and new pharmaceutical preparations in hospital, to fill in the domestic vacancies, to reduce the cost of medical treatment and to facilitate the clinical application.
Methods: on the basis of the existing literature, the preparation and process of the slow-release tablets of methicylcyclic acid were prepared and optimized. The reversed phase high phase liquid chromatography, Diamonsil C18, 0.23% liquid phase twelve alkyl sulfate solution methanol (60:40, V/V), detection wavelength 220nm, flow velocity 0.8mLmin-1 temperature 30; A sample size of 20 UF L. was used to determine the chromatographic conditions and verify the method, and determine the feasibility and reliability of the established method.
1 preparation process: pre - prescription study, in vitro release degree as the main index, the effect of various factors on drug release behavior were investigated in detail from prescription factors and technological factors, and the best prescription and technology were determined according to the research results.
2 quality research and standard formulation: Research on drug properties, identification, inspection, content determination, etc., establish the methodology of release degree, microbial limit, related substance and content determination, and establish a perfect, feasible and controllable quality standard.
The stability study of 3 preparations: the stability influence factor test on methicyclic acid sustained-release tablet, the accelerated test, the long-term test, the key examination items with the character, the release degree, the related substance, the content, the microbial limit and so on, to examine the effect of temperature, humidity and light on its quality, in order to determine its validity.
Conclusion: 1 select HPMC as the sustained-release skeleton of hydrophilic gel, and select the best prescription: methicyl acid 650mg, microcrystalline cellulose 28mg, micropowder silica gel 2G, preformed starch 31mg, K4 155g, polyvidone (K30) 53mg, stearic acid 20mg, magnesium stearate 11mg. with wet granulation, hardness 18 ~ 20kg, tablet weight as
2 adopt the appendix XD second method of the Chinese Pharmacopoeia >2010 edition, with water, 0.1mol L-1 hydrochloric acid, pH4.5 acetate buffer and pH6.8 phosphate buffer as release medium.
900mL, the release of methicyclic acid sustained-release tablets in different release media was studied by RP-HPLC method. It was preliminarily determined that the release of this product from 15 to 30min was 40 to 50%, 45 to 90min release 90%, and 98 to 100%. released from 120 to 150min to prove that the release amount of methicinic acid could be released in the prescribed time.
The excipients in the 3 preparation did not affect the content determination of methicyclic acid sustained-release tablets. The peak area and concentration of methicyclic acid sustained-release tablets in the range of 0.5007 ~ 4.0056mg mL-1 showed a good linear relationship (r=0.9999), the detection limit and the quantitative limit were 1.024,3.413gg, and the average recovery was 98 to 102% (RSD% < 2%, n=9).
4 the results of the stability test showed that the influence factor test of this product was 10d, the accelerated test was 6 months, and the inspection indexes of the long-term test for 9 months had no obvious changes compared with the 0d. All of them were within the qualified range, and their stability was good and the period of validity was tentatively fixed for 2 years.
5 the indexes of sustained release tablets of homemade tranexamic acid were similar to those of imported tranexamic acid sustained-release tablets.
By establishing a reversed phase high performance liquid chromatography (RP HPLC), the release degree of methicyclic acid sustained-release tablets was investigated and the quality standard was established. The results show that the method is accurate, simple and rapid, and can be used to control the quality of methicyclic acid sustained-release tablets.
【學位授予單位】：湖南師范大學
【學位級別】：碩士
【學位授予年份】：2014
【分類號】：R943

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本文編號：1979183