The present invention provides an anhydrous crystal of polymyxin B1 sulfate, polymyxin B2 sulfate or a mixture thereof and a preparation method thereof. The preparation method comprises using an organic solvent to precipitate a solid from a saturated solution of polymyxin B1 sulfate, polymyxin B2 sulfate or a mixture thereof, drying it under vacuum to obtain an anhydrous crystal of polymyxin B1 sulfate, polymyxin B2 sulfate or a mixture thereof.

The present invention provides an anhydrous crystal of polymyxin B1 sulfate, polymyxin B2 sulfate or a mixture thereof and a preparation method thereof. The preparation method comprises using an organic solvent to precipitate a solid from a saturated solution of polymyxin B1 sulfate, polymyxin B2 sulfate or a mixture thereof, drying it under vacuum to obtain an anhydrous crystal of polymyxin B1 sulfate, polymyxin B2 sulfate or a mixture thereof.

A secondary fatty acyl component of varying length was added onto the polymyxin structure at the amine side-chain of L-diaminobuytric acid at position 1, resulting to the development of dilipid polymyxins. The incorporation of an additional lipid was found to confer to polymyxin activity against Gram-positive bacteria, to which polymyxins are inherently inactive against The dilipid polymyxins showed selective antibacterial activity against Pseudomonas aeruginosa. Moreover, dilipid polymyxin 1 that consists of four carbon-long aliphatic lipids displayed the ability to enhance the antibacterial potency of other antibiotics in combination against P. aeruginosa, thereby resembling the adjuvant activity of the well-known outer membrane permeabilizer polymyxin B nonapeptide (PMBN).

A secondary fatty acyl component of varying length was added onto the polymyxin structure at the amine side-chain of L-diaminobuytric acid at position 1, resulting to the development of dilipid polymyxins. The incorporation of an additional lipid was found to confer to polymyxin activity against Gram-positive bacteria, to which polymyxins are inherently inactive against The dilipid polymyxins showed selective antibacterial activity against Pseudomonas aeruginosa. Moreover, dilipid polymyxin 1 that consists of four carbon-long aliphatic lipids displayed the ability to enhance the antibacterial potency of other antibiotics in combination against P. aeruginosa, thereby resembling the adjuvant activity of the well-known outer membrane permeabilizer polymyxin B nonapeptide (PMBN).

Provided are compounds of formula (III), and the use of compounds of formula (III) in methods of treatment, such as methods of treating a microbial infection. The compounds of formula (III) is: where —R.sup.15 is an amino-containing group: and —R.sup.1, —R.sup.2, —R.sup.3, —R.sup.4, —R, —R.sup.A, Q, —R.sup.16, —R.sup.17 are as described in further detail in the description.

##STR00001##

Provided are compounds of formula (III), and the use of compounds of formula (III) in methods of treatment, such as methods of treating a microbial infection. The compounds of formula (III) is: where —R.sup.15 is an amino-containing group: and —R.sup.1, —R.sup.2, —R.sup.3, —R.sup.4, —R, —R.sup.A, Q, —R.sup.16, —R.sup.17 are as described in further detail in the description.

##STR00001##

It relates to polymyxin analogues having a disulfide bond and an amino alcohol group adjacent to the disulfide bond, and optionally, an ester bond in the peptide backbone, which are useful as antibacterial agent, as well as to pharmaceutical compositions comprising them. It also relates to a key intermediate compound of formula (II) and its preparation process.

The invention provides a polymyxin compound of formula (I) and salts, solvates and protected forms thereof, pharmaceutical compositions comprising the compounds of formula (I), and the use of the compounds and compositions in methods of treatment, such as methods for the treatment of microbial infections. The compounds of formula (I) are represented thus:

##STR00001## wherein —R.sup.15 is a group:

##STR00002## and —R.sup.16 is hydrogen; —R.sup.17 is hydrogen -L- is a covalent bond or methylene; and —Ar is optionally substituted aryl. The groups —X—, —R.sup.1, —R.sup.2, —R.sup.3, —R.sup.4, and —R.sup.8 are as defined herein.

The invention provides a polymyxin compound of formula (I) and salts, solvates and protected forms thereof, pharmaceutical compositions comprising the compounds of formula (I), and the use of the compounds and compositions in methods of treatment, such as methods for the treatment of microbial infections. The compounds of formula (I) are represented thus:

##STR00001## wherein —R.sup.15 is a group:

##STR00002## and —R.sup.16 is hydrogen; —R.sup.17 is hydrogen -L- is a covalent bond or methylene; and —Ar is optionally substituted aryl. The groups —X—, —R.sup.1, —R.sup.2, —R.sup.3, —R.sup.4, and —R.sup.8 are as defined herein.

Field of application: The invention relates to combinatorial chemistry, pharmacy and cosmetology, allows to synthesize new combinatorial libraries of derivatives of antibiotics for use in pharmacy, cosmetology and pharmacy.

Technical result: modified combinatorial derivatives of antibiotics with antimicrobial and antifungal activity against multiresistant and pan drug resistance strains of microorganisms and fungi. Means have a wide spectrum of action, and the supramolecular and combinatorial structure of their tens and hundreds of derivatives eliminates the resistance of microorganisms.