| Cerebrovascular disease is one of the biggest killer of human health threat, dividedinto ischemic cerebral vascular disease and hemorrhagic cerebrovascular disease. Amongthem, ischemic cerebral vascular diseases accounted for about70%, and can be dividedinto transient cerebral ischemia, cerebral infarction. The incidence of cerebral vasculardisease in the population over40years old is increasing in our country with theimprovement of living standards, worse still,the youth incidence is increasing year byyear, and has high morbidity, mortality rate, high recurrence rate. Therefore, the perevention and treatment of ischemic cerebrovascular disease have very importantsignificance.Changhai Hospital Preparations Toutongling has been applied in clinical more than30years,and welcomed by doctors. Also,Toutongling has played a major role in one ortwo grade prevention and treatment of ischemic cerebrovascular disease. However,Toutongling has lots of applications inconvenience. Since the drug is the mixture of oiland water system,it’s not stable.And the main active ingredient lactone in aqueoussolution is easy to degrade. Therefore, Toutongling has strict requirements for pH,storage temperature and storage time. In addition, Toutongling is not easy to carry andtake for patients.Soft capsule is a new dosage form, has played a tremendous role in the reform offorms of Chinese medicine. It has a beautiful appearance, taste better, highbioavailability.Therefore soft capsule is well received.Researchers have considered to change Toutongling into soft capsule, andcompleted the following four aspects. First of all, method extracting volatile oil ofLigusticum chuanxiong were screened, mainly according to the extract yield, contentsdifferences, pharmacological effects. Ultimately they choose the subcritical CO2method.Secondly, they have established the quality standard of Rhizoma Chuanxiong volatile oil.Thirdly, they tested the stability of volatile oil to determine the storage conditions ofchuanxiong oil. Last but not the least, they have investigated the material made of thesoft capsule.This thesis has completed the amplification production of Chuanxiong volatile oilsoft capsule, and established the quality standards of the amplified soft capsule,determined the stability, pharmacodynamics, acute toxicity, chronic toxicity and other aspects of the soft capsule.In the first part of this paper, we verified the pilot scale-up process of Chuanxiongrhizome volatile oil soft capsule.Also,we investigated the types and amounts ofplasticizer, opacifier, preservatives, combined with the actual demand forindustrialization. The optimal prescription is gelatin: Glycerin: water: iron oxide red:paraben=100:40:100:2.1:0.14,.According to the prescription,we producted three batchessoft capsule.In the second part of this paper, we established the quality standards of the softcapsule, according to Chinese Pharmacopoeia (2010Edition) under the rules ofpreparations, including the appearance, identification, disintegration time, contentdetermination, microbial limit and so on.In the third part of this paper, we completed the stability test in accordance with theChina Pharmacopoeia (2010Edition),including high temperature and high humidity,illumination, results showed that the volatile oil of Ligusticum chuanxiong Hort softcapsule in high temperature, high humidity and light conditions are unstable. Based on thetest results of influence factors, accelerated test and long-term test were studied todetermine the storage conditions. Summarily, the soft capsule should be in cool storage andadopt the double aluminium packaging.In the fourth part of this paper, pharmacodynamics of soft capsule has beendetermined.Relied on the model of MCAO, the rate of cerebral infarction andneurological deficit score has been studied. Ligusticum chuanxiong volatile oil softcapsule, in low, middle,high dose (30,100,300mg/kg) has been determined, resultsshowed that the soft capsule (30and100mg/kg) can significantly reduce the acutecerebral ischemia injury, improve the neurological score.Acute toxicity tests were investigated in the fifth part of this paper.The resultssuggested the soft capsule by gavage on mouse LD50is1594.92mg/kg, its95%confidence limit is1443.80~1765.51mg/kg. Chuanxiong volatile oil soft capsule in ratsby intragastric administration of LD50for2115.24mg/kg, its95%confidence limit is1849.86~2438.34mg/kg.The sixth part of the paper has finished long-term toxicity test of the soft capsule.The results show that rats given soft capsule100~1000mg/kg for28days, their safedose (NOAEL) are300mg/kg, the toxic dose are1000mg/kg. The main toxicity is foodintake and body weight growth slowed down, the elevation of BU. Clinical use should pay attention to effects on the digestive system and urinary system. This part provides atheoretical and practical basis for the clinical trials.In summary, this paper carried out pilot scale-up of Chuanxiong rhizome volatile oilsoft capsule. In accordance with the Chinese Pharmacopoeia2010version, weestablished the quality standards and finished the stability test. Furthermore, Chuanxiongvolatile oil soft capsule pharmacological and toxicological studies have been completed,providing reliable data for pre clinical study of Chuanxiong volatile oil soft capsule. |
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