| Acute pharyngitis, frequently encountered in clinic and usually presented as one composingpart of upper respiratory tract infection, refers to the acute infection involving pharyngealmucosa, submucosa and surrounding lymphatic tissue, which may happen alone orsecondary to acute rhinitis, in autumn or winter mostly. Acute pharyngitis is mainly causedby virus, such as coxsackievirus, adenovirus, parainfluenza virus, rhinovirus, influenzavirus, or bacteria, streptococcus, staphylococcus, streptococcus pneumoniae, for instance.As a result, antiviral agents or antibiotics are mainly used in clinic for this condition,Traditional Chinese Medicine has good effect as well.Scutellaria, or Scutellaria baicalensis Georgi, is one herbal medicine commonly used inclinic, with chromocor total as it’s main ingredients composed of baicalein, wogonin,wogoain-7-o-glucuronide, oxoxylin, etc. Scutellaria, bitter in flavor, cold in property, actingon the lung, gall bladder, spleen, large intestine and small intestine channels, has the effectof clearing away heat and fire, removing dampness and toxic material, thus is widely usedin clinic and commonly used for acute pharyngitis as well.Excessive clinical use has resulted in immoderacy culling and digging of the herb;exhaustion of herbal resource has emerged. Traditionally, the medicinal part of scutellaria isthe root of the herb, with the stack and leaf discarded which is actually an enormouswasting. The purpose of the research is to exploit the usage of stack and leaf of scutellaria,extend its medicinal part, and thus increase its use value, which is of great social andeconomic importance. Experimental study has proven that, chromocor total extracted fromscutellaria is a high-effective and low-toxicity material, possesses the effect of anti-virus,anti-bacteria, anti-inflammation, antipyretic, analgesic and regulating immune system. One in vitro anti-virus experiment shows that chromocor total from scutellaria stack andleaf could evidently inhibit cytopathic effect caused by over 10 kinds of viruses, such asCOXB3, COXB4, COXB5, influenza virus, parainfluenza virus, etc. One in vivoexperiment shows that this herbal substance has markable inhibitory effect to viralpneumonia in mice, with lung index and the grade of lung disease in research group lowerthan that in control group, dosage-dependent related, this herbal substance has variableinhibitory effect to mice death caused virus as well.Another in vitro experiment shows that this herbal substance presents variablebacteria-killing or bacteriostatic effect to 31 kinds of bacteria, such as staphylacoccusaureus, pseudomonas aelugmosa, staphylococcus, streptococcus,α-hemolytic streptococcusorβ-hemolytic streptococcus, etc. Another in vivo experiment indicates it has certainprotecting effect to mice death caused by staphylacoccus aureus infection, which isdosage-dependent to some extent, more evident in large or moderate dose group.Anti-inflammation experiment shows, this herbal substance has certain anti-imflammationeffect to acute inflammatory reaction of mice auricle caused by dimethylbenzene, and couldinhibit acute inflammatory reaction of mice toes caused by egg white, dosage-dependentevidently.Anti-pyretic experiment shows, this herbal substance could inhibit pyretic reaction of rabbitcaused by E.COIi Endotoxin to different extent, dosage-dependent as well.Analgesic experiment shows that this herbal substance has some influence on pain reactionin mice caused by vinegar, dosage-dependent to some extent as well.Experiment of influence on immune system shows, this herbal substance has effects on thehumoral immune function or cellular immune function in mice to a different degree, largeor moderate dose could promote the production of hemolysin antibody in mice or sheep.Non-clinical studies mentioned above have established well-founded basis for clinicalresearch, human tolerance clinical trial and efficacy and safety assessment clinical trial were conducted afterwards.Purpose of human tolerance clinical trial is to investigate the tolerance and safety of capsuleof chromocor total from scutellaria stack and leaf in human being with healthy volunteers,providing basis for phase 2 medication regimen.Based on the result of dog Beagle long-term toxicity experiment, 1000 mg/kg/d has causedtoxic symptoms and reversible change of internal organs, considering the clinical feasibilityand dose recommended by sponsor as well, maximum dose of Phase 1 trial waspreliminarily suggested to be 3550 mg, about 10 capsules. Research result suggests, thenon-side effect dose for single dose is 170mg to 1520mg, the maximum tolerated dose is1520mg, about 4 capsules.Founded by human tolerance clinical research, phase 3 clinical trial of efficacy and safetywas conducted with the main purpose of evaluating clinical efficacy of the capsule intreating acute pharyngitis of wind-heat type through observing the transformation of mainsymptoms before and after treatment such as pharyngalgia, dryness and burning sensationin throat, swelling in pharyngeal mucosa and uvula. One of the secondary purposes is toobserve the change of subordinate symptoms and that of peripheral white blood cell count,differential count of white blood cell, the other is to evaluate it’s safety through observeblood routine, urine routine, stool routine, the function of heart, liver or kidney and therelated adverse events.460 subjects were enrolled in phase 3 clinical trial, 8 withdrawals, 8 protocol deviation case,both accounts for 3.48％. Finally, data were analyzed on the basis of FAS and PP analysis.By PP analysis, the overall effective rates of trial and control group were 57.78％and54.05％, the CL of 95％CI for non-inferiority test is -8.36％, there is significance betweentrial and control group by non-inferiority test. 95％CI for the discrepancy of overalleffective rates is between -10.68 and 18.14. By FAS analysis, the overall effective rates oftrial and control group were 57.18％and 53.91％, CL of 95％CI for non-inferiority test is-8.66％, there is significance between trial and control group by non-inferiority test. 95％CIfor the discrepancy of overall effective rates is between -10.95 and 17.49. These data proved the null hypothesis is true. Statistical analysis with test of superiority on symptomsafter treatment was done after that, it shows indicators of significance are as follow, scorereduce of pharyngalgia in research and control group are 3.88 and 3.19, P＜0.01; scorereduce of swelling in pharyngeal mucosa and uvula are 3.11, 2.62 respectively, P＜0.05;overall score reduce are 11.93, 10.14 respectively, P＜0.05.One subject in research group had got slight increase in ALT and AST which returned tonormal in following up examination with neither intervention nor unblinding, ALT is 28U/L before study, 59 U/L after, AST is 34 U/L before, 49 U/L after, investigator judged therelationship with the research drug to be suspicious; one subject in the same group hadslight increase in BUN, 8.7mmol/L, returned to normal with no intervention nor unblinding,investigator judged to be impossible. One subject in control group had diarrhea, statisticalanalysis shows there is no significance between the two groups.Human tolerance clinical trial and clinical tiral on it’s efficacy and safety has proved thatcapsule of chromocor total from scutellaria stack and leaf is effective and safe in treatingacute pharyngitis of wind-heat type, superior to Yinhuang capsule. The overall research isfundamental to the exploitation and making use of medicinal resource of scutellaria stackand leaf, which bears significant social value. |
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