| Qingkailing hard and soft capsule has qingrejiedu, tranquilize mind, clinically used in upper respiratory tract infection, viral cold, acute suppurative tonsillitis, acute pharyngitis, a variety of diseases such as high fever. Qingkailing formula science spirit, antibacterial, antiviral, anti-inflammatory effect is good, is a commonly used traditional heat-clearing and detoxifying, which enjoys a good green traditional Chinese medicine of antibiotics. Qingkailing has been made into a variety of preparations, roughly divided into two categories, injection and oral.In recent years because of the influence of traditional Chinese medicine injection adverse opinion agitation, oral medicine preparation, the more popular with the public.Research report, injections reported a majority, but the related research rarely oral preparation, the main around a single dosage form, and previous studies on the comparative study between various dosage forms less attention, lead to the clinical application of different dosage forms, characteristics and advantages are unclear.Because is various and complex prescription compatibility of traditional Chinese medicine compound chemical composition, the attending diversity, only continue to use the modern western medicine research point of view to compare between different formulations of traditional Chinese medicine compound, difficult to objectively reflect the overall condition of the compound. Based on component quantitative analysis combined with chemical pattern recognition method, in accordance with TCM treatment based on overall, dialectical system theory, can be observed in different dosage forms for overall evaluation.Based on this, this topic in the current clinical application of a wide range of 2 kinds of oral Qingkailing capsule preparation -- ordinary hard capsules and soft capsules as the object, systematic comparison study between the two, provide the basis for clinical reasonable application of oral preparations;Using multicomponent quantitative combination of chemical pattern recognition technology, observation of the different dosage forms for overall evaluation of the consistent with the overall concept of traditional Chinese medicine theory, systemic, can really apparent itself characteristics and advantages of Chinese traditional medicine.Concrete research content is as follows:1 Based on the multicomponent quantitative combination of chemical pattern recognition technology of Qingkailing soft/hard capsule quality control material for basic researchUsing HPLC-DAD, established the soft/hard capsules five major component content determination method, Cholic acid and hyodeoxycholic acid, chlorogenic acid, geniposide,baicalin in 0.10044～1.00440mg/mL,0.10140～1.01400mg/mL,0.00124-0.06208 mg/mL,0.00194-0.09720mg/mL,0.02118～1.05920mg/mL,good linear relation, The precision of the instrument, method repeatability, sample stability and average sample recovery rate all meet the requirements. By content determination results, soft/hard capsules in cholic acid and geniposide, baicalin content in pharmacopoeia content limit range.According to the clinical oral dose calculation, hard capsule of cholic acid and hyodeoxycholic acid, chlorogenic acid, geniposide, baicalin content were soft capsule of 1.002,1.19,8.2,1.63,0.92 times, cholic acid and hyodeoxycholic acid and baicalin content there was no significant difference, but the obvious differences in contents between chlorogenic acid and geniposide.Using HPLC-DAD, established the soft/hard capsule fingerprint method, the precision of the instrument, the stability of the method repeatability, sample are accord with the requirement of fingerprints.Results indicate the soft capsule of 21 common peak, a total of peak area accounts for 87.18% in total.Marking out the hard capsule 16 common peak, a total of peak area accounts for 84.40% in total.Not eliminate clear open spirit of baicalin soft/hard capsules each batch fingerprint similarity above 0.99, excluding baicalin after each batch similarity above 0.92, shows that soft/hard capsule no large difference between each batch.The chemical pattern recognition method to overall evaluation of the quality control, after eliminating baicalin PCA analysis the similarity is more in line with the actual situation.By PLS model similarity and the relationship between the variables, find out the similarity between batches with soft/hard capsule closely related markers, one of the markers for baicalin, has included in the pharmacopoeia quality limits, suggesting the need will not included in other quality limit range markers on quality control standards.By adopting the method of chemical pattern recognition analysis chemical differences between soft/hard capsules.PCA and PLS analysis results show that there exists significant difference between the two formulations,59 chemical components concentration in soft capsule high,40 chemical components concentration in hard capsule high, get difference between the two of the biggest contribution to the 16 elements.2 Based on the multicomponent quantitative combination of chemical pattern recognition technology of Qingkailing soft/hard capsules stability studyThrough long term stability test, during the test in 0,1,2,3,6 month sampling, using HPLC to detect, determine the content of major ingredients and the corresponding fingerprint, component degradation index curve comparison between the two.Results within six months of hard and soft capsule five ingredients have the degradation index, but none of the percentage content of less than 90%,5 kinds of component degradation in hard and soft capsules that are slower.Among them, the soft capsule of cholic acid and hyodeoxycholic acid and baicalin degradation is hard capsule is slow, but gardenoside faster than hard capsule degradation, chlorogenic acid both are basically identical.For each sampling time data statistics show no difference.Can be tentatively suggest that, for the major components, both hard and soft capsule in 1-6 months can maintain good stability.By principal component analysis and system clustering analysis method to analysis the whole fingerprint data.Principal component analysis results show that the hard and soft capsules have significant differences.Six months before the soft capsule of high data similarity, prompt stability is better, but three months before the hard capsule data similarity is higher, but after 6 months to reduce data similarity, prompt sample stability is poorer. System clustering analysis results show that the sample was divided into two categories, soft hard capsule has significant difference.The hard capsule and continue to split into smaller categories,6 months hard capsule samples with three months before the sample was divided into two categories, hints of the sixth month of the hard capsule samples and the samples of the first three months of difference is bigger, part how hard capsule as soft capsule is stable.It consistent with the results of principal component analysis.3 Based on the multicomponent quantitative combination of chemical pattern recognition technology of Qingkailing soft/hard capsule in rats with gastric perfusion fluid, intestinal perfusion liquid stability differences in research.Qingkailing Soft/hard capsule in gastric perfusion liquid incubation method is:in the preparation of artificial gastric juice, the preparation of stomach perfusion fluid, soft hard capsule and the stomach perfusion fluid is common in 37 ℃ water bath shaking table for vibration, a total of 4 h incubation.Sampling time point 1,5,10,15,30,60,90,120,90 min, chromatographic methods using the above content determination and fingerprint method.Soft/hard capsule incubation with the rat stomach perfusion fluid get the following results:Soft capsule in about 15 min break a small mouth, hard capsule started a component dissolution in 1 min.Soft capsule of three active ingredients (chlorogenic acid, geniposide, baicalin) is a slow process of dissolution, various components within the stomach perfusion fluid dissolution quantity gradually increase slowly, the accumulation of 4 hours of cumulative dissolution quantity is less than 15%.Hard capsule of chlorogenic acid and geniposide is also a process of gradually release, the perfusion fluid in the stomach gradually increase the cumulative dissolution quantity (within 15 min of chlorogenic acid and geniposide in cumulative dissolution quantity can reach about 50%, and within 4 h of chlorogenic acid accumulation has reached around 75%, the dissolution quantity gardenoside cumulative dissolution quantity 90%);And hard capsule group stomach perfusion liquid baicalin is first rise in fast around 10%(5 min), then lower (down to 4%).Soft/hard capsule contents incubation with the rat stomach perfusion fluid get the following results:Soft capsule contents of three effective ingredients (chlorogenic acid, geniposide, baicalin) is a process of gradual dissolution, concentration is increasing (4 h after the chlorogenic acid and geniposide release around 45%, baicalin release less than 5%).Hard capsule contents of chlorogenic acid and geniposide is a rapid dissolution at first, followed by incubation liquid concentration in the slowly rising process (15 min concentration release reached 70%,4 h concentration released after about 90%);And baicalin in hard capsule is first rapid dissolution fast around 10%(5 min), then slowly lower (down to 4%).Capsule and contents in rat stomach perfusion liquid compare get the following results: Soft capsule contents under the condition of no capsule shells, drug dissolution than capsule shells, when things faster, and that contents of four hours after the percentage content of perfusion fluid in the stomach is capsule in the stomach perfusion liquid content percentage is high, show soft capsule shell will slow the rate of drug dissolution.Hard capsule because capsule shells, in the beginning of the concentration of the drug dissolution was lower than those of contents, the concentration is close to, but after four hours both showed the presence of capsule shell to the release of the drug and the degradation of the impact is not big.By using PCA analysis get soft capsule in most of the ingredients in gastric perfusion liquid is a process of gradual dissolution, concentration is increasing.Hard capsule in most of the ingredients in gastric perfusion liquid is a gradually dissolution at the beginning, the middle period reached the highest concentration and lower process.Soft/hard capsule in the fluid of the intestinal perfusion incubation method is:artificial intestinal juice preparation, preparation of intestinal perfusion fluid, soft hard capsule and the intestinal perfusion fluid is common in 37 ℃ water bath bed ZhongZhen wave, a total of 24 h incubation.Sampling time point 5,15,30,60,90,120,90,120,480,720,1080,1440 min, with the method of content determination and fingerprint chromatography method.Experimental results show that Three active ingredients of soft capsule (chlorogenic acid, geniposide, baicalin) in intestinal perfusion fluid is a gradually dissolve out first, after balancing process.Three components initially slow dissolution, completely in about 6 h dissolution (around 90%) the cumulative dissolution quantity, thereafter until 24 h concentration remained at around 93%.Hard capsule of three active ingredients in the intestinal perfusion liquid is first rapid dissolution (2 h cumulative dose around 90%), then lower (down to 80%). Soft capsule of chlorogenic acid in metabolism, geniposide, baicalin 24 hours remaining are soft capsule residual ratio is higher than hard capsule.PCA analysis obtain most of soft capsule ingredients in intestinal perfusion fluid is a beginning gradually dissolution, concentration is increasing, reached after dissolution and degradation of balance, drug concentration keep relative balance of a process.Hard capsule in most of the ingredients in the intestinal perfusion fluid is beginning of a rapid dissolution (about 2-4 h dissolution were highest), then reduce. |
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