Development of a new class of drugs as anti-Sepsis-Medicament and as general Microbiozide

General remarks

The assessment of infections has been changed completely in the last 30 years. Whereas still in the 1980’s it was believed that all bacterial infections were controllable with antibiotics (Fig. 1), now it is the general view that  bacterial infections are a worldwide threatening of human health, in developed states they are the third frequent, in countries of the ‚Third World‘ they are even the most frequent cause of death.  

Figure 1: Assessment of infectious diseases more than 30 years ago

Figure 2: Assessment of infections 20 years later


Beside the direct threatening by bacteria or their ‚pathogenicity factors‘ (bacterial products, which are responsible for the outbreak of inflammations), bacterial infections are frequently also a result of a preceding viral infection. The well-known example for this is the ‚Spanish Flue‘, which in the 1920ies led worldwide to 20-30 millions death cases. Causes of death for most of the infected people was not the virus, but the subsequent bacterial infection (‘superinfection’) leading to ‘blood poisoning’ (medicinal: sepsis). In a similar way is this valid for the so-called swine flu, for which, however, up to now only few death cases were observed.

Also the occurrence of bacterial resistance, caused by wrong medication of antibiotics, but mainly by the excessive use of antibiotics in animal husbandry, represents an increasing threatening. Well-known germs are MRSA (methicillin- or multi-resistant Staphylococcus aureus), VRE (vancomycin-resistant enterococci), and FQRP (fluorquinone-resistant Pseudomonas aeruginosa).

In the last decades pharmaceutical companies have brought to market only two new classes of antibiotics, which moreover had only effects against particular bacteria. Problematic is this fact with respect to the occurrence of a septic shock, which may occur for patients, whose body is weakened due to other traumata (heavy burns, accidents, surgery etc.), who have a weak immune system, or who were infected due to unfortunate reasons. Numbers in Germany alone are depressing: Officially are annual rates of approximately 70.000 deaths, but the real rates are probably much higher (estimates are 150 000 in: ‚Bild der Wissenschaft 2/2011). This large  discrepancy may be due to the fact, that physicians frequently state as reason of death lung inflammation or organ failure, which, however, are final symptoms of a septic shock.

Development of a sepsis

One of the causes of a severe infection leading to sepsis, which in more than 50 % of cases leads to death in critical care units, is the release of bacterial toxins (endotoxins, lipoproteins) from the call envelopes of bacteria. These toxins react with cell of the immune system in a heavy, uncontrollable way by producing so-called   cytokines (mediators), which leads to a self-poisoning of the body.

Figure 3: Mechanisms of LPS-induced cytokine (mediators) secretion with subsequent induction of sepsis.

Unfortunately, the use of antibiotics in this situation frequently does not improve the health of the patients, but in contrary worsens their state, because due to bacterial killing the bacterial toxins are now released from the bacterial cell envelopes with a severe increase in the inflammation reaction.

Figure 4:  Assessment of physicians from critical care units: Problems with the antibiotic treatment of patients. The labelled text means: ‘There are more and more results from animal models and from clinical studies that the antibiotic-induced release of biologically active LPS leads to a worsening of the critical state of septic patients.’


In many cases not the bacteria from outside (from the environment or from the body’s surface) are responsible for the infection, but body-own (endogeneous) bacteria, which originate from an inner body region (in most cases from the gut) and penetrate into the blood circulation, followed by a heavy systemic inflammation (see Fig. 5).

Figure 5:  Concentrations of bacterial Endotoxin (LPS) in different body regions


Most importantly, this means that not whole bacteria, but their toxins are responsible for the triggering of a sepsis. This implicates that in critical care units in the blood often no bacteria are found, but the patient is nevertheless heavily ill. The nomenclature of the different symptomatic is illustrated here:




Occurrence of Lipopolysaccharide (Endotoxin) in Blood


Occurrence of Living Bacteria in Blood

Systemic Inflammatory Response
Syndrom (SIRS)

Generalized hyperinflammatory reaction with different causes, Infections, Burns, Traumata


SIRS induced by an Infection

Severe Sepsis

Sepsis with Organ Dysfunction

Septic Shock

Sepsis with Shock

New broad-range Antiseptics

We have developed a new class of drugs, called SALP (synthetic anti-lipopolysaccharide peptides), which are designed directly to neutralize the inflammation-inducing bacterial toxins, and less to kill bacteria. The toxins are lipopolysaccharide (LPS, endotoxin) in the case of Gram-negative and lipoproteins in the case of Gram-positive bacteria. We have found that the binding affinity of our SALP to these toxins is so high that the latter do not react anymore with the human binding proteins, which leads to the strong inflammation.

The project is in an advanced preclinical phase, in which according to national and international regulations the tolerability of the SALP must be proven in two animal models (rat and mini-pigs).

Market potential

Some words about the market potential: The costs for the treatment of sepsis patients in critical care units in the USA amount approximately 17 billion $ annually. Estimates  assume that 1/3 of all costs in critical  care units come from the treatment of sepsis patients. According to the German Kompetenz-Netzwerk Sepsis (SepNet) and the Deutsche Sepsis-Gesellschaft e.V. the costs are alone in Germany around 1.8 billion € annually, this means the septic syndrome is additionally also a huge economic problem. Newer estimates in the meantime assume that the real sum is much higher.

Anyway, the turnover of a good medicament against sepsis should lie in the range of some billions Euros annually. This can be, among others, deduced from the fact that the drug Drotrecogin Alpha (Xigrisã von Lily), which was suitable only for a small portion of sepsis patients (some %), and was withdrawn in October 2011 due to unsufficient effectivity, had a turnover of 192 million $ annually .

Antiviral  activities

Beside the anti-septic action the SALP are also able to inhibit viral infections. This is true for various flu viruses (for example seasonal influenza H3N2), for some Herpes iruses (labial and genital herpes as well as cytomegalo virus), for the human immune deficiency virus HIV, for hepatitis B and C and the human papilloma virus.

HIV-infections and the AIDS-disease resulting from this are a large medicinal challenge: According to the world health organisation (WHO) at the end of 2006 39.5 million people were infected worldwide, with a tendency of drastic increases of newly infected people in Eastern Europe and Central Asia. In North America and Western Europe 65,000 new infections are observed, and in these parts of the world there are presently 2,1 millions infected people. Approximately 1/3 of these patients are treated with highly active anti-retroviral therapy (HAART). The annual market volume for HIV-medicaments alone in North America and Western Europe can be estimated to be 10 billion Euro, and can be assumed to increase for many years due to the worldwide increasing infection rates.

Approximately 350 million people are chronically infected with hepatitis B worldwide, leading in many cases to liver cirrhosis and liver cancer. There exists a vaccine for hepatitis B, but no therapeutic agent. This is valid in a similar way for the treatment of the seasonal flu, and also for the swine flu (serotype H1N1).

Thus, a SALP medicament is available which has a broad range application possibility.