JPH0419968B2 - - Google Patents

Description

[Detailed description of the invention]

The present invention uses diaminodiphenylsulfone (DDS) and 2,4-diamino-5-
A novel pharmaceutical preparation containing a mixture of (4-bromo-3,5-dimethoxybenzyl)-pyridine (brodimoprim). The invention also relates to the use of a combination of substances as described above for the treatment of leprosy and/or other mycobacterioses. The use of DDS for the treatment of leprosy is known. Surprisingly, a mixture of DDS and brodimoprim was found to be effective against leprosy-causing organisms.
It has now been found that the compound exhibits a additively increased activity against the enzymes (Organisms) compared to the activities of the individual components. In a preferred embodiment, the preparations provided by the invention contain the above actives in a molar ratio of DDS to brodimoprim of 1:1 to 1:10. The significant complementary activity of the combination of DDS and brodimoprim according to the invention against leprogenic organisms is evident from the tests described hereinafter. bovine serum albumin
albumin) (Fraction V) 0.25 weight/volume%
A modified Dubos-Davis nutrient solution was inoculated with Mycobacterium lufu from a 4-6 week old Gottsacker agar slant culture. To obtain a homogeneous suspension, the bacteria were
After homogenization in 15 ml of medium, the suspension was diluted in 15 ml of medium and centrifuged at 150 g for 4 minutes.
A portion of the supernatant was used for culture production. The suspension was diluted to approximately 10 ⁵ cells/ml and 50 ml aliquots were added to a 300 ml Erlenmeyer culture flask equipped with a magnetic stirrer. Inhibitors were added and cultures were kept at 31°C. Cultures were vigorously stirred magnetically for 1 minute before removal of the test for counting. Counting was done on a Coulter counter. To determine total bacterial counts, culture samples were diluted with particle-free sodium chloride (0.85%/formaldehyde (0.2%)) solution to obtain between 500 and 20,000 organisms. To determine live bacterial counts, 0.5 ml samples were removed from time to time, added to 50 ml of fresh nutrient solution, and incubated at 31°C. Cultures were counted on a Coulter counter after 8 days as described above. Determined by changes in the growth rate of cultures in the presence of specific inhibitors. To this end, the rate constant Kapp [sec ^-1 ] for the observed first-order generation rate in the absence and presence of an inhibitor is determined by the formula log N = K _app t/2.303 + log No (where N is defined as was determined from the increase in the growth curve according to the number of organisms in the culture volume, where t is the time in seconds and No is the number of bacteria at the point at time t=0. Results for DDS-susceptible mycobacteria (M.lufu)
and DDS resistance (
100μMDDS) are listed in the table for mycobacteria (M.lufu). A constant is given for the steady-state developmental rate for M.lufu at 31°C in the presence of various inhibitors at various concentrations.

【table】

【table】

Table: In the presence of the active substance combination provided by the invention, no microbial growth was observed and even a decrease in the number of live bacteria in the culture was observed, whereas the active substances individually The values given in the table indicate that, if present, the culture continues to grow, albeit at a slower rate. DDS-resistant cultures are treated with DDS at appropriate concentrations.
- Also completely inhibited by the brodimoprim combination. The pharmaceutical preparations provided by the invention contain the active substance combinations with a compatible pharmaceutical carrier. The carrier may be an organic or inorganic inert carrier material suitable for intradermal, transdermal, or parenteral administration, such as
It can be water, gelatin, gum arabic, lactose, starch, magnesium stearate, talc, vegetable oil, polyalkylene glycol, petrolatum, etc. The pharmaceutical preparation is a fever-lowering agent, a pain-lowering agent, and a pain-relieving agent.
It may also contain other pharmaceutically valuable substances such as alleviating-agents, etc. Pharmaceutical preparations can be administered orally, for example, in the form of tablets, capsules, pills, powders, granules, solutions, syrups, suspensions, elixirs, and the like. However, administration may be for example parenteral in the form of a sterile solution, suspension, or emulsion or in the form of a solution, suspension, ointment, powder,
It can also be administered locally in the form of an aerosol or the like. The pharmaceutical preparations may be sterilized and/or may contain ingredients such as preservatives, stabilizers, wetting agents, emulsifiers, salts for osmotic pressure considerations, and buffer substances. The preparations provided by the invention can be used for the treatment of leprosy, even DDS-resistant leprosy. The preparation is used for non-medical control treatment of leprosy.
It is particularly suitable for avoiding the development of resistance in DDS therapy and in the case of DDS monotherapy. For therapeutic use, the preparation provided by the invention can be administered to adults at a daily dose of 50 mg-100 mg DDS and a corresponding amount of brodimoprim. The above doses can be administered as a single dose or in several sub-doses divided over the day. Preferably one tablet is administered per day. The following are examples of typical dosage forms: Tablet DDS 100mg Brodimoprim 200mg Primojel (starch derivative)
6mg Povidone K30 (Povidone) K30 (Polyvinylpyrrolidone) 8mg Magnesium stearate 6mg Total weight 320mg

Claims (1)

Claims: 1. An antimycobacterial composition comprising diaminodiphenylsulfone and 2,4-diamino-5-(4-bromo-3,5-dimethoxybenzyl)-pyrimidine. 2. The composition according to claim 1, which is used for the treatment of leprosy and/or other mycobacteriosis. 3 The molar ratio of diaminodiphenyl sulfone to 2,4-diamino-5-(4-bromo-3,5-dimethoxybenzyl)-pyrimidine is from 1:1 to 1:
10. The composition according to claim 1, wherein the composition is