本文選題：工藝參數(shù) + 近紅外��； 參考：《北京中醫(yī)藥大學(xué)》2017年碩士論文

【摘要】：目的:凝膠貼膏是中藥外用制劑的常用劑型,是中醫(yī)兒科等臨床優(yōu)勢病種廣泛運用的現(xiàn)代中藥制劑。然而,中藥凝膠貼膏工藝參數(shù)通常采用感官和經(jīng)驗判斷,缺乏客觀和量化的評價體系,本文采用近紅外技術(shù)、近紅外成像技術(shù)和流變學(xué)等新技術(shù),辨識凝膠貼膏制備過程的關(guān)鍵質(zhì)量屬性,分析中藥提取物的加入對凝膠貼膏成型的影響,優(yōu)選影響凝膠貼膏成型過程的關(guān)鍵工藝參數(shù)。方法:1.市售凝膠貼膏質(zhì)量情況的研究(1)以6種不同品質(zhì)等級市售凝膠貼膏為研究對象,采用黏附性指標實現(xiàn)不同品質(zhì)等級市售凝膠貼膏的評價。(2)首次采用近紅外成像技術(shù),采用基礎(chǔ)相關(guān)性分析方法(BACRA)對6種市售凝膠貼膏表面成像圖進行分析,通過統(tǒng)計自相關(guān)的近紅外成像光譜相關(guān)性計算結(jié)果,實現(xiàn)市售凝膠貼膏的表面均勻性評價。2.在課題組前期實驗的基礎(chǔ)上,以小兒退熱處方為載體,采用外觀性狀結(jié)合高分子流變學(xué)技術(shù)以及近紅外成像技術(shù),研究中藥浸膏的加入對中藥凝膠貼膏成型的影響。(1)將提取所得的中藥提取物濃縮成相對密度在1.0～1.4之間的浸膏,制備不同中藥提取物密度的凝膠貼膏對其進行黏附力及感官評價。(2)采用流變學(xué)技術(shù)測定了不同相對密度中藥提取物制成的凝膠貼膏膏體的線性粘彈區(qū)(LVR)、復(fù)數(shù)模量G*、彈性模量G'、粘性模量G"等指標,研究加入不同中藥提取物制成的凝膠貼膏膏體的內(nèi)部性質(zhì)。(3)采用近紅外成像技術(shù)對自制的加入不同相對密度中藥提取物的凝膠貼膏表面近紅外光譜掃描,通過近紅外成像圖及對膏體表面光譜進行統(tǒng)計,考察不同密度中藥提取物制備的凝膠貼膏的表面均勻性。3.采用近紅外技術(shù)監(jiān)測中藥凝膠貼膏成型過程中的的幾個關(guān)鍵質(zhì)量屬性(1)采用近紅外成像技術(shù)判斷不同時間點物料混合的均勻性,確定了凝膠貼膏制備過程中的最佳攪拌時間。(2)采用近紅外光譜技術(shù),通過移動塊標準偏差法(MBSD)計算方法,監(jiān)測凝膠貼膏制備過程中基質(zhì)的交聯(lián)反應(yīng),確定了不同處方的快速交聯(lián)反應(yīng)時間,通過測定每隔24h膠強度變化率驗證了用近紅外光譜判斷凝膠貼膏交聯(lián)反應(yīng)終點的科學(xué)性。(3)通過體外釋放實驗,測定凝膠貼膏基質(zhì)不同交聯(lián)時間藥物釋放度來判斷凝膠貼膏基質(zhì)的交聯(lián)程度,驗證采用近紅外光譜技術(shù)判斷交聯(lián)反應(yīng)終點的可靠性。結(jié)果:1.市售凝膠貼膏質(zhì)量情況的調(diào)研(1)6個品牌的市售凝膠貼膏的初黏力和剝離強度差異較大;研究進一步得出初黏力在能粘住不小于9號小球的范圍內(nèi)均屬合格,剝離強度在-0.11N--0.48N范圍內(nèi)屬合格,以此獲取了中藥凝膠貼膏黏附力合格范圍。(2)6個品牌成像圖的可視化輪廓表達了不一樣的均勻程度,品牌6光譜相關(guān)性的相對標準偏差高達23%,說明品牌6的凝膠貼膏表面分布非常不均勻,而品牌3的相對標準偏差最小,分布較均勻。本部分為后期自制中藥凝膠貼膏的指標評價提供了方法和技術(shù)支撐。2.采用近紅外成像結(jié)合高分子流變學(xué)技術(shù),研究中藥提取物的加入對中藥凝膠貼膏成型的影響。(1)中藥提取物的相對密度對凝膠貼膏成型的影響較大,提取物密度影響凝膠貼膏的粘接性能及交聯(lián)強度。當(dāng)中藥提取物的相對密度為1.12時,凝膠貼膏的外觀性狀較好,不滲布,且黏性均較好。(2)當(dāng)中藥提取物的相對密度為1.12時,基質(zhì)的復(fù)數(shù)模量G*值和線性粘彈區(qū)(LVR)較大,結(jié)果表明膏體結(jié)構(gòu)強度大并且結(jié)構(gòu)穩(wěn)定,表現(xiàn)出"強凝膠"的特性。本部分發(fā)現(xiàn)了凝膠貼膏表面性質(zhì)和內(nèi)部性質(zhì)存在相關(guān)性,獲取了較優(yōu)凝膠貼膏的系列指標,為后期中藥凝膠貼膏制備提供了技術(shù)和指標支撐。(3)當(dāng)加入的中藥浸膏的相對密度為1.049和1.12時,凝膠貼膏表面光譜之間的相對標準偏差為1%,表面分布較均勻,此方法取代了只用肉眼觀察的感官指標產(chǎn)生的差異,使中藥凝膠貼膏的評價更標準化、客觀化。3.采用近紅外技術(shù)監(jiān)測中藥凝膠貼膏制備過程中的的幾個關(guān)鍵質(zhì)量屬性(1)在膏體混合至20min時,膏體表面光譜的吸光度差別最小(RSD=0.01),中藥浸膏膏體已經(jīng)混合均勻,因此最終確定當(dāng)物料混合20min后形成的凝膠膏體表面較均勻且利于涂布。(2)近紅外光譜可以監(jiān)測到膠強度24h變化率為10%左右光譜的變化,當(dāng)膠強度24h的變化率低于10%時,即凝膠貼膏體系進入慢速反應(yīng)期,近紅外光譜測得的凝膠貼膏表面光譜無變化。通過對比不同處方制備的凝膠貼膏的膠強度及交聯(lián)反應(yīng)時間,發(fā)現(xiàn)得出了各物料對凝膠貼膏膠強度及交聯(lián)反應(yīng)速度的影響。(3)通過測定不同交聯(lián)時間藥物累積釋放率,3個處方分別在72h,72h,120h時,所含藥物的累積釋放率最大,說明此時3個處方的凝膠貼膏在快速交聯(lián)反應(yīng)終點的附近。本實驗的結(jié)果與采用近紅外光譜技術(shù)監(jiān)測得到的交聯(lián)反應(yīng)終點的時間基本一致,可以驗證近紅外光譜技術(shù)判斷交聯(lián)反應(yīng)終點的可靠性。結(jié)論:本文采用多種新技術(shù)嘗試構(gòu)建了中藥凝膠貼膏成型工藝參數(shù)篩選和成品的質(zhì)量評價方法體系。采用近紅外成像技術(shù)實現(xiàn)了市售凝膠貼膏和自制凝膠貼膏表面均勻性評價,使凝膠貼膏的評價更客觀、準確;采用流變學(xué)技術(shù)發(fā)現(xiàn)了不同處方制備的凝膠貼膏的內(nèi)部性質(zhì),找出了中藥提取物的加入對凝膠貼膏基質(zhì)的影響,比較了不同處方下凝膠貼膏的黏附性及粘彈性,并確定了最優(yōu)處方;采用近紅外光譜技術(shù)實現(xiàn)了凝膠貼膏成型過程中的關(guān)鍵質(zhì)量參數(shù)監(jiān)測并發(fā)現(xiàn)了最優(yōu)參數(shù)值;本文構(gòu)建的方法體系使中藥凝膠貼膏的評價更加準確、客觀,保證了凝膠貼膏的質(zhì)量均一、穩(wěn)定、可控。
[Abstract]:Objective: gel paste is a common dosage form of traditional Chinese medicine for external use. It is a modern traditional Chinese medicine preparation which is widely used by clinical dominant diseases such as pediatrics of traditional Chinese medicine. However, the technical parameters of gel paste are usually judged by sensory and experience and lack objective and quantitative evaluation system. Near infrared imaging technology, near infrared imaging technology and rheology are used in this paper. The new technology identifies the key quality attributes of the gel paste preparation process, analyzes the effect of the addition of Chinese medicine extract on the gelation of gel paste, and selects the key technological parameters that affect the gelation process of gel paste. Method: Study on the quality of gel plaster in the 1. cities (1) to study the gel plaster of 6 kinds of different quality grades. The adhesion index was used to evaluate the gel ointment of different quality grades. (2) the surface imaging of 6 kinds of gel paste was analyzed by the near infrared imaging technique and the basic correlation analysis method (BACRA) was used for the first time. The surface of the market gel paste surface was realized by the statistical autocorrelation calculation of correlation near infrared imaging spectra. On the basis of the preliminary experiment of the project group,.2. was used as the carrier of the antipyretic prescription of the children. The effect of the addition of the Chinese herbal extract on the gelation of the traditional Chinese medicine gel paste was studied by using the appearance character, the polymer rheology technology and the near infrared imaging technology. (1) the extract of the extracted Chinese medicine was condensed into a relative density of 1 to 1.4. The adhesive force and sensory evaluation of the gel ointment with the density of different Chinese herbal extracts were prepared. (2) the linear viscoelastic area (LVR), the complex modulus G*, the elastic modulus G'and the viscosity G "G" were measured by rheology. The internal properties of the gel paste paste made of the material. (3) near infrared scanning of the gel paste surface with different relative density of Chinese herbal extract with near infrared imaging technology, and the surface of the gel paste prepared by different density Chinese herbal extracts were investigated by the near infrared imaging and the statistics of the surface spectrum of the paste. The homogeneous.3. uses near infrared technology to monitor several key quality attributes in the forming process of traditional Chinese medicine gel plaster (1) using near infrared imaging technology to determine the uniformity of material mixing at different time points, and determine the optimum stirring time in the process of gel paste preparation. (2) using near infrared spectroscopy and mobile block standard deviation method (MBSD ) the calculation method was used to monitor the crosslinking reaction of the matrix in the gel paste preparation process and determine the rapid crosslinking reaction time of different prescriptions. By measuring the change rate of each 24h glue strength, the scientific character of the near infrared spectrum to judge the crosslinking reaction end point of gel paste was verified. (3) the different crosslinking of the gel paste matrix was determined by the release experiment in vitro. The degree of time drug release was used to determine the crosslinking degree of the gel paste matrix, and the reliability of the crosslinking reaction end was determined by near infrared spectroscopy. Results: 1. research on the quality of the gel plaster (1) the difference of the initial adhesion and stripping strength of the 6 brands of the market gel paste was different. The range of no less than No. 9 is qualified, and the peeling strength is qualified within the range of -0.11N--0.48N, so as to obtain the qualified scope of the adhesive force of the traditional Chinese medicine gel paste. (2) the visual contour of the 6 brand image maps expressed the different degree of uniformity, and the relative standard deviation of the brand 6 spectral correlation is as high as 23%, indicating the gel paste of the brand 6. The surface distribution of the paste is very uneven, while the relative standard deviation of the brand 3 is the smallest and the distribution is more uniform. This part provides a method and technical support for the index evaluation of the later homemade traditional Chinese medicine gel paste. The effect of the addition of Chinese medicine extract on the gelation of the traditional Chinese medicine gel has been studied by the method and technical support.2.. (1) The relative density of the extract of traditional Chinese medicine has great influence on the gelation of gel paste, and the density of the extract affects the adhesion and crosslinking strength of the gel paste. When the relative density of the extract of Chinese medicine is 1.12, the appearance of the gel paste is better, and the stickiness is better. (2) when the relative density of the extract of Chinese medicine is 1.12, the matrix is recovered. The G* value of modulus and the linear viscoelastic zone (LVR) are large. The results show that the structure of the paste is strong and the structure is stable, showing the characteristics of "strong gel". This part found the correlation between the surface properties and the internal properties of the gel paste, and obtained a series of better gel paste, which provides the technology and index for the preparation of the later gelatin plaster. Support. (3) when the relative density of the Chinese herbal extract is 1.049 and 1.12, the relative standard deviation between the surface spectrum of the gel paste surface is 1% and the surface distribution is more uniform. This method takes the place of the difference of the sensory indexes only observed by the naked eye, so that the evaluation of the gel paste is more standardized, and the objective.3. is used in the near infrared technology monitoring. Several key quality attributes in the preparation of the gel paste (1) when the paste is mixed to 20min, the absorbance difference of the surface spectrum of the paste is minimal (RSD=0.01), and the extract paste has been mixed evenly. Therefore, the surface of the gel paste formed when the material is mixed with 20min is more uniform and is beneficial to coating. (2) near infrared spectroscopy can be used. The change rate of the adhesive strength 24h is about 10%. When the change rate of the adhesive strength 24h is below 10%, the gel paste system enters the slow reaction period and the gel paste surface spectrum of the gel paste has no change. The effect of the material on the strength of gel adhesive and the rate of cross-linking reaction. (3) the cumulative release rate of the drugs was the largest by measuring the cumulative release rate of drugs at different crosslinks at 72h, 72h and 120h, indicating that the gel paste of 3 prescriptions was near the fast crosslinking reaction end point at this time. The results of this experiment and the use of the near infrared light were the result of this experiment. The time of the cross-linking reaction end of the spectrum technology is basically the same, it can verify the reliability of the near infrared spectroscopy to determine the crosslinking reaction end point. Conclusion: in this paper, a variety of new technologies are used to construct the method of screening the processing parameters of the gelatin plaster and the quality evaluation method of the finished product. The near infrared imaging technology is implemented. The evaluation of the surface uniformity of the gel paste and the homemade gel paste made the evaluation of the gel paste more objective and accurate. The internal properties of the gel paste prepared by different prescriptions were found by the rheology technology, and the effects of the addition of the extract on the gel paste matrix were found out, and the adhesion and adhesion of the gel paste under different prescriptions were compared. The optimal prescription was determined by elasticity, and the key quality parameters in the gelation process were monitored by near infrared spectroscopy and the optimal parameter was found. The method system constructed in this paper made the evaluation of the gel paste more accurate and objective, and the quality of gel paste was guaranteed, stable and controllable.

【學(xué)位授予單位】：北京中醫(yī)藥大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2017
【分類號】：R283.6

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