PAs(Pyrrolizidine Alkaloids)

一、台灣常見含PAs之生藥

請參考由台中市藥用植物研究會刊印的台灣藥用植物雜誌第十二期。

http://johnwu0919.pixnet.net/blog/post/456269729

 

二、歐洲藥品管理局(european medicines agency)標準

採樣方法:  Commission Regulation 401/2006/EC (METHODS OF SAMPLING FOR OFFICIAL CONTROL OF THE LEVELS OF MYCOTOXINS IN FOODSTUFFS)

http://eur-lex.europa.eu/LexUriServ/LexUriServ.do?uri=OJ:L:2006:070:0012:0034:EN:PDF

 

檢驗之PAs

PA EMA-8.jpg

 

檢驗方法: an official analytical method is available Marketing Authorisation Holders (MAHs) are advised to use the SPE-LC-MS/MS method as published by BfR (Federal Institute for Risk Assessment: BfR-PA-Tea-2.0/2014). Other suitable validated methods may be acceptable.

http://www.bfr.bund.de/cm/349/determination-of-pyrrolizidine-alkaloids-pa-in-plant-material.pdf

 

檢驗限量: the HMPC view is that patient exposure to PAs from HMPs should be as low possible and should not exceed a daily intake of 0.35 μg. However, for a limited transitional period an intake up to 1.0 μg per day can be accepted. 

PA EMA-8.1.jpg

 

風險管理

1. The main approach for risk management of the PA contamination of herbal medicinal products should be according to the concept of ALARA, i.e. as low as reasonably achievable. 
2. In principle, contamination of herbal substances with PA containing weeds should not occur at all for reasons of requirements on pharmaceutical product quality and compliance with GACP/GMP. However, based on toxicological considerations and the current guidelines for risk assessment/management of genotoxic carcinogens, a contamination level leading to a daily intake of maximum 0.35 μg PAs/day (life-long exposure for a person with a body weight of 50 kg) is considered of low safety concern
3. A contamination level of herbal medicinal products leading to a daily intake of maximum 1.0 μg PAs/day during a transitional period of 3 years is acceptable from a public health point of view, for reasons discussed above. During this time period the producers of herbal medicinal products should take actions necessary to reduce the contamination to a level leading to a daily intake not exceeding 0.35μg PAs/day. 

 

備註:EMA檢驗最終產品,尤其關注採收過程混入之含PAs之雜草。

 

 

三、WHO, IPCS風險評估

WHO-14.jpg

WHO, International Program on Chemical Safety(IPCS).

Health and Safety Guide No. 26 :PYRROLIZIDINE ALKALOIDS HEALTH AND  SAFETY GUIDE

 

四、千里光、款冬花PAs推算

藥材名稱

來源

中國藥典2015年版

建議劑量

所含主要PAs

藥典PA限量

PA擬攝入量*

EMA標準

千里光

菊科植物千里光 Senecio scandens Buch.

-Ham. ex D. Don的乾燥地上部分

15~30公克

Senecionine; Seneciphylline;

Adonifoline

本品按乾燥品計算,Adonifoline不得過0.004%

(水分不得過14%)

516~1032μg Adonifoline/day

(按乾品計,合格品之極量)

1.0 μg PAs/day

款冬花

菊科款冬 Tussilago farfara L.的乾燥花蕾

5~10公克

Senecionine; Senkirkine

-

50~180μg/day

1.0 μg PAs/day

*千里光擬Adonifoline攝入量,依據中國藥典2015年版之限量標準、建議用量推算。

  款冬花PAs攝入量,依據“《中國藥典》含吡咯里西啶生物鹼的中藥品種與用藥安全”一文所載。

 

小結

1、國外管理含PAs藥材或產品的概念是: ALARA (as low as reasonably achievable),一般,我們會說中藥有炮製或透過增長煎煮時間來減少毒性,然實際情如何,恐也須評估。

2、國內廠商若要做外銷生意,就須符合當地標準才做得到生意。嚴格是好,寬鬆是好,可能與產品價值等息息相關,也就是科學也需考量民生與民情等等因素。

3、生藥中,如黃野百合(豆科野百合屬植物)種子為台灣市售沙苑子的偽品,稱為本沙苑子。如錯用於可能會久服之中藥方劑中(如金鎖固精丸),恐需多留意藥材之正確性,才不致產生問題。

4、生活中食材的觸及率與食用量恐是更須留意。

 

 

參考資料:

1、台灣藥用植物雜誌,第十二期,台中市藥用植物研究會。

2、中國藥典。

3、歐洲藥品管理局(European Medicines Agency ),Public statement on contamination of herbal medicinal products/traditional herbal medicinal products1 with pyrrolizidine alkaloids.31 May 2016 

4、WHO, International Program on Chemical Safety(IPCS).Health and Safety Guide No. 26 :PYRROLIZIDINE ALKALOIDS HEALTH AND  SAFETY GUIDE

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