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The synthesis of isoxazole-based derivatives utilizing Baylis-Hillman chemistry and results of their preliminary bioevaluation as hypolipidemic agents in triton model are described.
Twenty patients with nodulocystic acne were randomly allocated to one of two treatment schedules: 1) Tetracycline 500 mg or 2) Tab. Gugulipid (equivalent to 25 mg guggulsterone). Both were taken twice daily for 3 months, and both produced a progressive reduction in the lesions in the majority of patients. With tetracycline, the percentage reduction in the inflammatory lesions was 65.2% as compared to 68% with gugulipid; on comparison, this difference was statistically insignificant (P > 0.05). Follow-up at 3 months showed a relapse in 4 cases on tetracyline and 2 cases on gugulipid. An interesting observation was that the patients with oily faces responded remarkably better to gugulipid.
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The study was conducted at a primary school in Abis 8 village. 88 children aged eleven years consented to participate in the present study. After fecal examination, 43 (48.8%) cases were found infected with Cryptosporidium. The mean oocysts number per high power field (HPF) ranged from (1.6-48 oocysts/HPF). Azitbromycin, praziquantel (PZQ) and mirazid were given to 13, 16 and 14 infected children respectively. Three weeks after treatment, azithromycin and praziquantel gave cure rates of 91% and 56.2% respectively with a percent reduction of oocysts in stools of 99% for azithromycin and 71.5% for PZQ. Mirazid was not effective. All the three drugs were well tolerated. It was concluded that azithromycin is highly effective in the treatment of children with cryptosporidiosis: PZQ decreases the infection rate and intensity.
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Multicentric clinical trials of the efficacy of gugulipid conducted at Bombay, Bangalore, Delhi, Jaipur, Lucknow, Nagpur and Varanasi have been reported. Two hundred and five patients completed 12 week open trial with gugulipid in a dose of 500 mg tds after 8 week diet and placebo therapy. One patient showed gastrointestinal symptoms which did not necessitate withdrawal of the drug. A significant lowering of serum cholesterol (av. 23.6%) and serum triglycerides (av. 22.6%) was observed in 70-80% patients Double-blind, crossover study was completed in 125 patients with gugulipid therapy and in 108 patients with clofibrate therapy. Two patients had flu-like syndrome with clofibrate and opted out from the study. With gugulipid the average fall in serum cholesterol and triglycerides was 11 and 16.8% respectively and with clofibrate 10 and 21.6% respectively. The lipid lowering effect of both drugs became evident 3-4 week after starting the drug and had no relationship with age, sex, and concomitant drug intake. Hypercholesterolaemic patients responded better to gugulipid therapy than hypertriglyceridaemic patients who responded better to clofibrate therapy. In mixed hyperlipidaemic patients response to both drugs was comparable. HDL-cholesterol was increased in 60% cases who responded to gugulipid therapy. Clofibrate had no effect on HDL-cholesterol. A significant decrease in LDL-cholesterol was observed in the responder group to both drugs.
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Cholesterol containing diet significantly increased not only the body weight, but also the weight of liver and adipose tissue of rats. This is accompanied by a significant increase in blood lipids, atherogenic index and lipid peroxidation and a significant decrease in reduced glutathione level, superoxide dismutase and catalase activities in tissues. Treatment with S-allyl cysteine sulphoxide reverses the deleterious effects of cholesterol diet significantly and almost as effectively as gugulipid.
The effect of single oral dose of 1 gm gugulipid was studied on bioavailability of single oral dose of propranolol (40 mg) and diltiazem (60 mg) in 10 and 7 normal healthy male volunteers respectively. It was a randomised within group crossover study. Blood samples were collected at hourly intervals upto 8 hrs. Gugulipid significantly reduced (P < .01) peak plasma concentration (Cmax) and area under curve (AUC 0-8 hrs) of both the drugs in normal volunteers. Such interaction in patients receiving propanolol or diltiazem with gugulipid may lead to diminished efficacy or nonresponsiveness due to significant reduction in bioavailability.