Download Sodium salt of 3-(4-cinnamyl-1-piperazinyl)-imino

A NEW DRUG WITH HIGH POTENCY FOR TREATMENT OF TYPICAL AND ATYPICAL (IN
IMMUNOCOMPROMISED PATIENTS), SENSITIVE AND MULTIDRUG RESISTANT TUBERCULOSIS.
3-(4-cinnamyl-1-piperazinyl)-imino-methyl rifamycin SV, Sodium salt - (T-11, Rifalong)
1. Chemical structure
The new product named Rifalong is member of the group of derivatives of 3-formyl-rifamicine SV.
Chemical Structure:
CH3
CH3
HO
H3C
H3CCOO
H3C
H3CO
OH
ONa
O
OH
CH3
H3C
NH
O
CH
N
N
N
CH2CH
CH
OH
O
CH3
O
Chemical name: 3-(4-cinnamyl-1-piperazinyl)-imino-methyl rifamycin SV, Sodium salt
CAS [277001-57-0]
2. Patent protection
The new chemical entity is patent protected in USA, Europe (all countries member of EC), Russia, India and Brazil.
3. Investigation made till now:
- Anti-mycobacterium activity in vitro and in vivo.
- Antibacterial activity in vitro (aerobe and anaerobe bacteria)
- Patho-morphological study on generalized tuberculosis in rats and guinea pigs with and without treatment by T11.
- Pharmacokinetics of T11 in experimental animals.
-Toxicological studies – acute toxicity (LD 50), chronic toxicity on 3-(4-cinnamyl-1-iminomethyl ) piperazinyl
rifamycin SV.
- Influence of 3-(4-cinnamyl-1-iminomethyl) piperazinyl rifamycin SV on drug metabolizing enzyme systems (DMES)
in rats.
- Experimental study on the anti-inflammatory action of 3-(4-cinnamyl-1-iminomethyl) piperazinyl rifamycin SV
- Neuro-pharmacological study of 3-(4-cinnamyl-1-iminomethyl ) piperazinyl rifamycin SV
- Antimicrobial activities against mycobacterium tuberculosis and mycobacterium avium complex
- Pharmacokinetics of cinnamyl rifamicin derivative in mice
- Pharmacokinetics of cinnamyl rifamicin derivative in rat and rabbits
- Clinical study “Open examination of effectiveness and tolerability of Rifacinna capsules 150 mg and 300 mg, in
treatment of pulmonary tuberculosis”, (Phase II)
- DMF of a new drug substance is prepared.
4. The main characteristics of the drug:
- Extremely high in vitro activity against clinical isolated strains of gram-positive and gram-negative (aerobic and
anaerobic) pathogens and tuberculosis mycobacterium including MAC and Mycobacterium Leprae.
- High in vitro and high intraphagocytic activity against MAC strains.
- Higher and more rapid therapeutic efficacy in vivo in generalized experimental tuberculosis in mice and guinea pigs.
- Lower hepato-toxicity of T-11 compared to Rifampicin;
- Lower immunosuppressive effect than Rifampicin.
- Higher activity against intracellular developing infections (Listeria monocytogenes and Mycobacterium Avium),
higher than Rifampicin and Rifapentine and equal with than of Rifabutin.
- No teratogenetic and embryo toxic effect in experimental animals.
- Excellent pharmacokinetic profile – rapid and complete absorption after oral administration, high and most prolonged
serum concentrations following single oral dose of 10 mg/kg (with T max 6-8 h, Cmax 7-8 g/ml, and plasma T1/2 31 h)
compare other Rifamycin antituberculous agents like Rifampicin, Rifapentine, Rifabutin.
- Bactericidal activity against MDR-strains of Mycobacterium TBCc (t. humans and MAC-strains isolated from AIDS
patients) comparable to activity of Rifampicin and Rifabutin.
- Prominent anti-inphlammatory effect and absence of ulcerogenic activity.
- Lower activation (5 times) of the liver drug-metabolising enzyme systems compared to Rifampicin.
- EXCELLENT CLINICAL EFFICACY OF RIFACINNA® IN TUBERCULOUS PATIENTS WITH PULMONARY
TUBERCULOSIS CAUSED EITHER SENSITIVE OR MDR STRAINS OF MYCOBACTERIA.
- Excellent tolerability and safety profile of RIFACINNA® in tuberculous patients treated with 10 mg/kg daily dose tree
time weekly.
- Most convenient dosage regiment of RIFACINNA® compare Rifampicin and Rifabutin- BEST COST EFFECTIVE COURSE OF TREATMENT.
- Additionally – excellent anti-Lepra activity (Prof. A.Dople)
5. The data of efficacy of T-11, resp. Rifacinna® was established in:
- Mycobacterium Department of Illinois University, Chicago, USA; (Prof. Gandgaharam, Assoc. Prof. V. Dimova).
- Microbiological and Immunological Institute, Shimane Medical University-Japan (Prof. Haruaki Tomioka, Assoc.
Prof. V.Dimova)
- Chemical Pharmaceutical Research Institute- Sofia, Bulgaria (Assoc. Prof. V.Dimova)
- Medical University- Institute of Pulmology and Tuberculosis- Sofia, Bulgaria (Prof. Radanov, Prof. Dobrev, Assoc.
Prof. V.Dimova)
- National Centre of Infectious and Parasitic Diseases- Sofia, Bulgaria (Prof. G. Gencheva, Assoc. Prof. E. Sapundjieva,
Assoc. Prof. T. Kantardjiev, Assoc. Prof. V.Dimova)
- Technical University – Melburn, Florida, USA (Prof. A. Dople, Assoc. Prof. V.Dimova)
- Department of Microbiology and Immunology, Haruaki Tomioka and Katsumasa Sato, Shimane University School of
Medicine, Izumo, Shimane 693-8501, Japan
- Academy of Medical Sciences of Ukraine, Institute for phtisiatry and pulmonology “ F. G. Yanovski” of the AMSc of
Ukraina (IFP)( Academic Feshchenko, Prof. Dr. L. O. Yashina, Assoc. Prof. A. M. Tumanov)
6. Medicinal product formulations:
RIFACINNA® – Capsules 150mg and 300mg.
RIFACINNA® Capsule 150mg - contains 150 mg Rifalong (Sodium salt of 3-(4-cinnamyl-1-piperazinyl)-imino-methyl
rifamycin SV)
RIFACINNA® Capsule 300 mg - contains 300 mg Rifalong (Sodium salt of 3-(4-cinnamyl-1-piperazinyl)-imino-methyl
rifamycin SV)
7. To finalize the investigation and to prepare the documentation necessary for registration we have to do:
- Bioavailability study in healthy volunteers (Phase I)
- Clinical study of the new medicinal product
8. What we are looking for:
We are looking for financial support to finalize the Rifalong investigations:
First step will be the bioavailability study of the product in healthy volunteers (Phase I).
If we do such a study in Bulgaria we will save money, as the bioavailability studies here are cheaper than abroad. For
this purpose we need about 100 000 euro.
Next step will be the clinical examination (in Bulgaria too, by the same reason) in treatment of pulmonary tuberculosis,
(Phase II).