Use of oligomers of lactic acid in the treatment of gynaecological disorders

#The present invention describes use of oligomers of lactic acid (OMLA) for the prophylaxis and/or treatment of gynaecological infections, such as microbial or viral infections, notably bacterial vaginosis. Moreover, the oligomeric products of the invention can be used in the treatment or prophylaxis of any disease or condition where an acid pH below about 4.0 or 4.5 is desired or as excipients releasing an acid during a prolonged period of time in order to maintain a suitably low pH in the environment. The invention also relates to novel oligomers of lactic acid as well as to novel oligomeric products containing specific mixtures of specific lactic acid oligomers. Specifically, the present invention relates to oligomers of lactic acid in the range from dimer to dodecamer and the use thereof. The oligomers are normally presented as a formulation e.g. in the form of a device or a kit.

#Gynaecological or reproductive tract infections generally refer to three different types of infection which affect the reproductive tract. Endogenous infections include bacterial vaginosis and candidosis, which result from an overgrowth of organisms which are normally present in the vagina. The endogenous infections represent the most common form of lower gynaecological tract infections (LGTIs) worldwide, and they can be easily treated. However they commonly reappear, which is a major medical problem.

#Iatrogenic infections represent a second group which occur when the infectious agent (a bacterium or other micro-organism) is introduced into the reproductive tract through various routes such as menstrual regulation, induced abortion, IUD insertion or during parturition. Finally. sexually transmitted infections (STIs) are caused by microorganisms such as viruses, bacteria, or parasitic microorganisms that are transmitted through sexual activity with an infected partner. Among the STIs there are several serious diseases such as HIV, chlamydia trachomatis, condyloma accuminata, syphilis and Neisseria gonorrhea. STIs can affect both men and women, but a transmission from mothers to children during pregnancy and childbirth may also occur.

#FIG. 1. OMLA 12 (dialysis sac)—changes of pH. When OMLA (substance) is placed in a dialysis bag, due to diffusion (OMLA and LA from degradation) pH of the outside aqueous compartment decreases. The pH change occurs for a long time; despite of replacing water outside of the dialysis bag after 3, 7 and 47 h. A) pH 1 h after replacing the liquid. B), C), and D) pH change through the periods between the exchange of water outside of the dialysis bag.

#FIG. 2. OMLA 31 (dialysis sac)—changes of pH. This is the same type of the experiment as FIG. 1, but with OMLA 31. The water was exchanged after 6, 46 and 88 hours. Less low-molecular components are present and the effect is weaker and slower as expected. FIG. 2A represents the pH value 1 h after replacing the liquid, and FIG. 2B-2D show pH change through the periods between the exchange of water outside of the dialysis bag.

#FIG. 3. The profile of release of free lactic acid from OMLA 31 (0.209 g) determined by titration with KOH using magnetic stirring in water at 20° C. The figure presents the quantity of acids (OMLA of low molecular weight and LA) dissolved in water. Half of the OMLA is probably of low molecular weight, whereas the rest dissolves slowly.

#Oligomers of lactic acid (OMLA) were produced by heating a commercial quality of lactic acid (LA), containing 85% LA and 15% water, at 120° C. in open tubes for different times, thus oligomerising LA to various degrees and producing products with varying viscosity. The number of the OMLA product (e.g. OMLA 12) indicates for how many hours it was heated.

#The various oligomers were characterised as described in Example 9.

#This experiment demonstrates the efficiency of OMLA as a source of acidic components and for retaining low pH for a prolonged time.