Mohs paste is an external preparation containing zinc hydrochloride and zinc oxide starch as the main ingredient, and it is used for the palliative treatment of patients with surgically untreatable malignant tumors. However, it has problems, such as changes in hardness and viscoelasticity with time and liquefaction by exudate. To overcome these problems, we modified the formulation of Mohs paste by excluding starch, which is the cause of physical changes, and investigated the base. In the modified Mohs paste using the macrogol ointment for the base, no marked change with time was noted in the hardness, malleability, or elongation property, and the water-absorbing properties were equivalent to those of Mohs paste immediately after preparation. The hardness did not decrease even after absorbing water. The drug release rate increased 1.5 times with the modified Mohs paste. Based on these findings, the risk of liquefaction-associated damage of the surrounding skin decreased on using the modified Mohs paste, and preparing in advance became possible. These results suggest that the modified Mohs paste using the macrogol ointment for the base exhibits an equivalent effect for control of exudate and a high effect for tissue fixation.

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1. Raloxifene is an antiestrogen that has been marketed for the treatment of osteoporosis, and is metabolized into 6- and 4'-glucuronides by UDP-glucuronosyltransferase (UGT) enzymes. In this study, the in vitro glucuronidation of raloxifene in humans and monkeys was examined using liver and intestinal microsomes and recombinant UGT enzymes (UGT1A1, UGT1A8 and UGT1A9). 2. Although the K(m) and CL(int) values for the 6-glucuronidation of liver and intestinal microsomes were similar between humans and monkeys, and species differences in Vmax values (liver microsomes, humans > monkeys; intestinal microsomes, humans < monkeys) were observed, no significant differences were noted in the K(m) or S50, Vmax and CL(int) or CLmax values for the 4'-glucuronidation of liver and intestinal microsomes between humans and monkeys. 3. The activities of 6-glucuronidation in recombinant UGT enzymes were UGT1A1 > UGT1A8 >UGT1A9 for humans, and UGT1A8 > UGT1A1 > UGT1A9 for monkeys. The activities of 4'-glucuronidation were UGT1A8 > UGT1A1 > UGT1A9 in humans and monkeys. 4. These results demonstrated that the profiles for the hepatic and intestinal glucuronidation of raloxifene by microsomes were moderately different between humans and monkeys.

Mohs paste (MP) is a hospital preparation containing zinc hydrochloride and zinc oxide starch. It is a topical medication used to fixate tissues for the removal of inoperable skin tumors and the management of hemorrhage and exudates, and to prevent foul odor resulting from secondary infections. However, it has problems, such as changes in hardness and viscoelasticity with time and liquefaction by exudate. It has been reported that the modified MP with D-sorbitol (S-MP) and the modified MP using the cellulose instead of starch (C-MP) have excellent physicochemical stability and better handling than original MP (O-MP). In this study, the effect of prescription improvement of MP on the pharmacological effect was examined with reference to water absorbing property, and its tumor tissue invasion fixation depth as an indicator. In the S-MP and C-MP, the amounts of water absorption did not differ significantly from those in the O-MP. The hardness of S-MP was decreased and liquefied like O-MP after absorbing water. In contrast, C-MP retained its form even after water absorption. The subcutaneous tumors in mice treated with modified MP formulations were measured for invasion fixation depth at 6 and 24 h after application. And the tissue status was observed using computed tomography. In all MPs, invasion fixation depth increased depending on application time. S-MP and O-MP depths did not differ significantly. The invasion depths of the C-MP significantly increased compared with those in the O-MP. These results suggest that C-MP had a high tissue fixation rate.

Massive bleeding induced by disintegration of breast cancer tumors for 4 yrs (88 yrs-old lady)was treated by applying Mohs＇ paste (75g/45mLof Zinc complex). This huge site healed quickly and the healing effects were sustained for 48 days. Based on this clinical evidence, the hemostatic mechanism of Mohs＇ paste was evaluated using the hind limb ischemia model in mice. Unilateral hind limb ischemia was induced in 6 week-old male C57BL/6JJmsSlc mice by resecting the right femoral and saphenous arteries. Mice were painted once a day with Mohs＇ paste containing 0, 37.5, 50 and 62.5g/45mL of zinc after the surgery. Hind limb blood perfusion was measured by using a laser Doppler perfusion imaging system (moorLDI2-Ⅱλ：S/N 5489). To identify capillaries, the thigh muscles were harvested on Day 1 to make a tissue section and immunostained for CD31. One day after painting of Mohs＇ paste, blood flow suppression to the ischemic leg was significantly enhanced in a dose dependent manner. Furthermore, anti-CD31 immunostaining revealed that Mohs＇ paste decreased capillary density in the ischemic muscle. The results of both the clinical and animal studies suggest that Mohs＇ paste suppressed angiogenesis due to the acute effects of aggregated protein and the sustained effects of decreases of CD31.