江油附子（黑顺片）产地加工炮制“减毒存效”的“四规律三原理”过程机理研究

Aconite is the lateral root of Aconitum carmichaeli Debx. ,which is well-known toxic drugs, the processing technique is an important guarantee for its safety and efficacy.Although the authentic region in Jiangyou has formed exquisite and unique processing technique ,some links of which were highly questioned , such as soaking with salt , drifting and so on. The concocting detoxification principle of the aconite is very explicit, but the process mechanism is unclear, including changes of processed aconite that the composition, potency, efficacy and toxicity have always been the comparison of "the beginning and the end ", meanwhile the principles including anti-corrosion,texture as well as color change in the processing of Aconite are still unknown..The group proposed: the aconite is changing in qualitative, property, effect and poison during the processing, the perfect combination of all the process and ultimately achieve the scientific hypothesis of the 'the attenuated deposit efficiency' meeting point. Yield the largest hei shun pian, bring in bacteria Isolation and identification of differential scanning rheological determination of the X-ray diffraction, the LC-MS, ICP-MS, to carry out "point chain binding (processed cooked links point - the aconite material state chain - accessories water liquid state chain) "system study, concluding the process mechanism that" four rules (composition, potency, efficacy, toxicity variation ) and three principles (antisepsis, texture, browning principle). "This topic is a good help to ensure the safety and effective of aconite; to promote the protection of the relevant skills about the intangible cultural heritage; and broaden the modern study ideas of the Traditional Chinese Medicine.

附子为毛茛科植物乌头子根的加工品，是著名的有毒中药，加工炮制是其安全有效的重要保证，道地产区江油形成精湛而独特的产地加工炮制技术，但自古泡胆、浸漂等环节饱受质疑。虽附子炮制解毒原理明确，但过程机理不清，如附子炮制前后成分、药性、药效、毒性变化均是"一头一尾"生品和制品的比较，且加工中胆巴防腐、附子质地和颜色变化的原理均未知。.本课题提出"附子在加工炮制过程中发生'质性效毒'的改变，各环节最佳工艺配合，使其最终达到'减毒存效'的最佳契合点"的科学假说。以产量最大的黑顺片为研究对象，采用菌种分离鉴定、热差示扫描、流变测定、X射线衍射、LC-MS、ICP-MS等技术，开展"点链结合（加工炮制环节点-附子物料状态链）"的系统研究，总结出"四规律（成分、药性、药效、毒性变化规律）三原理（防腐、质构、褐变原理）"的过程机理。有助于确保附子安全有效，促进相关非物质文化技艺保护，并拓宽中药炮制研究思路。

附子是典型的水火共制的产地加工炮制饮片，各环节最佳工艺配合，使其最终达到‘减毒存效’的最佳契合点”，存在“四规律三原理”的过程机理。. 研究表明，附子炮制过程前期总生物碱含量逐渐降低，后期略升高；双酯型生物碱明显降低；单酯型生物碱呈现升高-降低-再升高的趋势；生物碱类物质组成暂未见新成分的产生；4种水溶性成分（盐酸多巴胺、尿嘧啶、腺苷、鸟苷）在泡胆、切片漂洗均下降，最终稍降低或维持在较低水平；总多糖及外源性无机元素（胆巴）均在泡胆环节最高，而在漂附片环节最低，后期略有升高或变化不大。通过电子舌技术，对各环节点样品检测，发现“味”的变化与胆巴含量呈现极大的相关性。. 胆巴的加入对附子的药性（热性）明显降低，降低ATP酶活性、降低血清中ACTH含量、TSH含量和17-OHCS含量。同时胆巴会降低附子温补脾阳功效，漂净蒸制备后其作用有所增强，加工过程需将胆巴漂净。附子对中枢性疼痛镇痛作用较差，但有较好的治疗炎性疼痛的作用，但加工炮制后其散寒止痛功效有所降低。. 各环节样品水提液的急性毒性变化主要与胆巴的含量相关，基本不表现乌头碱类毒性。样品醇提液急性毒性，泥附子、漂附片主要与双酯型生物碱有关，胆附子、煮附子、冰附子是双酯型生物碱和胆巴中毒的共同反应；毒性大小顺序为：胆附子>煮附子>冰附子>泥附子>漂附片＞蒸附片，黑顺片基本无毒。对大鼠在体心脏毒性的影响，胆巴不会引起直接的心脏毒性，各样品点心脏毒性原因及强度与急性毒性类似。. 引起附子腐烂的病原微生物主要是真菌，亦有少量的细菌和放线菌，50%胆巴水溶液呈现出较好的抑菌效果，达到附子防腐的目的。在加工中，附子淀粉不仅经过了糊化和回生的物理变化过程，还伴随着晶体结构破坏的形成非晶化的无定形结构，并进一步重结晶形成更复杂的晶体结构，更加稳定。附子加工中可能发生的美拉德反应是其褐变的主要原理。