Bonhomme-Faivre L, Mathieu M C, Depraetere P, Grossiord J L, Orbach-Arbouys S, Puisieux F, Seiller M
Département de Pharmacie, Hôpital Paul-Brousse, Villejuif, France.
Drug Dev Ind Pharm. 1999 Feb;25(2):175-86. doi: 10.1081/ddc-100102158.
To tattoo human breast cancer prior to chemotherapy, radiotherapy, or surgery, thus allowing a better localization of the remaining tumor by the surgeon, we developed a formulation containing 10% charcoal suspended in water for parenteral preparations. The present study concerns a new step in the development of the charcoal suspension. We sought to determine whether the addition of various excipients could improve the formulation properties and affect the labeling of tumor by the suspension. We have tested surfactants (egg lecithin, polysorbate 80, Cremophor EL, and Pluronic F68), isotonisants (sugars such as glucose and mannitol), polysaccharides (dextrans 20 and 40), and Cabosil, a pyrogenated silica. Except for glucose and mannitol, which were added at a 5% concentration, the other excipients were added at a 0.1% concentration, they were dissolved in water for parenteral injection and sterilized at 120 degrees C for 20 min. We then measured diffusion in vivo in mammary tumor. In vivo, when injected intratumorally in mice, a greater diffusion of charcoal particles was noted within the tumor (in the case of egg lecithin, polysorbate 80, dextran 20 and 40, and glucose) and sometimes in some organs (e.g., Cremophor EL and mannitol). Pluronic F68 slightly improved the stability of the suspension and did not lead to marked diffusion at the injection site, but it showed slight toxicity and cannot be used in the formulation. We concluded that the best formulation was an aqueous 10% micronized peat charcoal suspension.
为在化疗、放疗或手术前对人类乳腺癌进行标记，从而使外科医生能更好地定位残留肿瘤，我们研发了一种用于非肠道制剂的配方，该配方含有10%悬浮于水中的活性炭。本研究涉及活性炭悬浮液研发的新步骤。我们试图确定添加各种辅料是否能改善配方特性并影响悬浮液对肿瘤的标记效果。我们测试了表面活性剂（卵磷脂、聚山梨酯80、聚氧乙烯蓖麻油和普朗尼克F68）、等渗剂（如葡萄糖和甘露醇等糖类）、多糖（右旋糖酐20和40）以及一种热原性二氧化硅——卡博西尔。除葡萄糖和甘露醇以5%的浓度添加外，其他辅料均以0.1%的浓度添加，它们溶解于非肠道注射用水中，并在120℃下灭菌20分钟。然后我们在乳腺肿瘤中测量了其体内扩散情况。在体内，当向小鼠肿瘤内注射时，观察到活性炭颗粒在肿瘤内有更大的扩散（在卵磷脂、聚山梨酯80、右旋糖酐20和40以及葡萄糖的情况下），有时在某些器官中也有扩散（例如聚氧乙烯蓖麻油和甘露醇）。普朗尼克F68略微改善了悬浮液的稳定性，且在注射部位未导致明显扩散，但它显示出轻微毒性，不能用于该配方。我们得出结论，最佳配方是10%的水性微粉化泥炭活性炭悬浮液。
