Abstract: Native Chinese herb medicine increases the detection in the new GMP standard microorganism project, restrict demand has increased for the traditional Chinese medicines, however, applicable sterilization method is also different, through several decades of efforts and expirences, the domestic major pharmaceutical companies has summarized the difference of disinfection sterilization methods, and propose reasonable scientific sterilization method for different sterilization load.
Sterilization of original powder of Traditional Chinese medicine herb refers to the method of killing or removing live pathogenic bacteria and microorganisms in original powder of traditional Chinese medicine and decoction pieces of Traditional Chinese medicine by appropriate physical or chemical means. In the production process of proprietary Chinese medicine, the sterilization result of the original drug powder has a great relationship with the quality requirements of the finished product. Therefore, before the original drug powder is put into medicine, the original drug powder exceeding the microbial limit must be sterilized in an appropriate way. The determination of the sterilization process of traditional Chinese medicine raw powder and decoction pieces of traditional Chinese medicine should comprehensively consider the nature of the sterilized raw powder, the effectiveness and economy of the sterilization method, the integrity and stability of the sterilized raw powder and other factors. The sterilization method should be verified before it can be delivered for formal use. In daily production, the operation of sterilization method should be monitored to ensure that key parameters (such as temperature, pressure, time, humidity, sterilizer ratio, sterilization gas concentration, etc.) are within the verified range. In addition, the sterilization method should be periodically retested. At present, the commonly used sterilization methods of traditional Chinese medicine raw powder and Chinese medicine decoction pieces include soaking method, steam sterilization method, dry heat sterilization method, ozone sterilization method, microwave drying sterilization method and radiation sterilization method. Due to the characteristics of Chinese medicinal materials, such as variety, complex nature and large difference in microbial content, when selecting sterilization methods, flexible selection and comprehensive utilization should be carried out according to the advantages and disadvantages of different sterilization methods.
Steam sterilization method refers to the method of killing bacteria by putting the original powder of Traditional Chinese medicine or decoction pieces of Traditional Chinese medicine into a sterilization cabinet and denaturating and solidifying the protein components in bacterial protoplasm with high pressure saturated steam. This method is one of the most effective and widely used sterilization methods in thermal sterilization. Wet heat sterilization conditions are usually “121’C, 15minutes” or “116°C, 40minutes”, other temperature and time parameters suitable for the product can also be used. In the whole process of production, it is necessary to strictly monitor the microbial contamination in the original powder of traditional Chinese medicine or Chinese medicine decoction pieces, and take measures to prevent heat-resistant bacteria from being contaminated, reduce the microbial contamination level, and ensure that the sterilized original powder reaches the microbial limit. When using steam sterilization, the sterilized traditional Chinese medicine powder or Chinese medicine yinpian should be properly loaded to ensure the effectiveness and consistency of sterilization.
Ozone elimination method is used to kill microorganisms in traditional Chinese medicine original powder or Chinese medicine decoction pieces by countercurrent contact with suspended ozone, which is carried out in a sterilization room filled with sterilization gas. In the sterilization room, according to the set procedures and conditions, make the powder in fluidization suspension state, prepare ozone by high pressure discharge method, and into the sterilization room, make it contact with the drug powder countercurrent, destroy treatment. Ozone sterilization conditions: ozone concentration 54g/m3, quenching time 40min, airflow speed 40Hz (frequency converter), oxygen purity > 85%, sterilization temperature W40°C, other suitable sterilization parameters for this variety can also be used. This method is suitable for the sterilization of primary drug powder which is stable in ozone. It has no harmful residue and will not harm the operator and the environment.
Dry heat sterilization method refers to the method of killing microorganisms with dry hot air by placing the original powder of Traditional Chinese medicine or decoction pieces of Traditional Chinese medicine in a dry heat sterilization cabinet (such as the tunnel drying, disinfection and sterilization machine of Bycotri). This method is suitable for the sterilization of primary medicine powder which is resistant to high temperature but not suitable for damp heat sterilization. Dry heat sterilization conditions are generally “115C, 90min”, other temperature and time parameters suitable for the variety can also be used. When using dry heat sterilization, the sterilized powder should be properly loaded to ensure the effectiveness of sterilization.
Microwave drying method is based on the principle of traditional Chinese medicine original powder or Chinese medicine decoction pieces being heated in high frequency electromagnetic field. Microwave rubbing with medicinal materials produces high heat and inactivates proteins, RNA and enzymes to achieve the purpose of sterilization. Usually microwave refers to electromagnetic waves with frequencies between 3.0×102-3.0x105NH2. Water can strongly absorb microwave, so that the polar molecule rotation, due to the friction between molecules and heat, heat is generated in the heated material, so uniform heating, heating up quickly. At the same time, microwave can penetrate into the inside of the original powder of TRADITIONAL Chinese medicine or the tablet of traditional Chinese medicine drink, so that the surface of the original powder of traditional Chinese medicine or the tablet of traditional Chinese medicine can be uniformly heated. After sterilization, the number of bacteria in the original powder of Traditional Chinese medicine or the prepared pieces of traditional Chinese medicine was 99% less than that in the untreated sample and dried. After microwave treatment, the effective ingredients of the original powder of Traditional Chinese medicine or decoction pieces of Traditional Chinese medicine are basically not destroyed, and the general sterilization time is 3 ~ 6min.
Radiation sterilization method refers to the method of killing microorganisms by putting the original powder of Traditional Chinese medicine or Chinese medicine decoction pieces into Y rays radiated by suitable radioactive source or electron beam produced by suitable electron accelerator. The most commonly used radiation sterilization method before is 60Co-Y ray radiation sterilization, the irradiation time is 24h to the original powder of Traditional Chinese medicine or Chinese medicine decoction pieces should be as far as possible with low radiation dose to destroy. Before sterilizing, the amount of microbial contamination and radiation resistance of the sterilized primary drug powder should be measured to evaluate the level of sterility assurance given to the sterilized product by the sterilization process. During sterilization, appropriate chemical or physical methods should be used to monitor the absorbed radiation dose of sterilized primary drug powder to fully prove that the absorbed dose of sterilized primary drug powder is within the specified limit (this sterilization method is not recommended).
|Method||Steam sterilize||Dry heat sterilize||Ozone sterilize||Microwave sterilize||Radiation sterilize|
|Time||About 1 hour||Few hours||About 1 hour||Few minutes||Electric bean|
|Condition||High temperature||High temperature||Room temperature||High temperature||Special room and facility|
|After sterilization||Cool down||Cool down||Stored to be decomposed||Cool down||N/A|
|Limit||High carbonhydrate and volatile herb is not suitable||High carbonhydrate and volatile herb is not suitable||Volatile herb is not suitable||Not suitable for heat sensitive herb and herb with low wwater content||Suitable for majority herbs|
|Bactrial/ %||99 〜100||78 〜95||93 〜98||82 〜95||98 〜100|
|Mold/ %||100||85 〜100||95 〜97||88 〜100||99 〜100|