Pharmacological properties and therapeutic activity of Russian-manufactured pulmonary surfactants

Abstract

Three pulmonary surthctant preparations: from human amniotic fluid, from bronchoalveolar lavage fluid, and from cattle lung tissue homogenate were tested in preclinical studies. The preparations are nontoxic, possess no mutagenic, teratogenic, and allergic activities and do not modify visceral morphology after repeated injections. After a single intratracheal administration the drugs normalize arterial blood oxygenation in 15-30 rain and arrest the respiratory distress syndrome in dogs, which is confirmed roentgenologically and clinically. Key Words: respiratory distress syndrome; surfactant; pharmacological properties; therapeutic activityThe respiratory distress syndrome (RDS) is one of the major causes of neonatal and adult mortality [3,5]. About 30,000 babies with RDS are annually born in Rnssia; in the USA 150,000 RDS cases are recorded annually in adults. In RDS 15-30% newborns and 50-70% adults die [3,5,7]. In preterm newborns RDS is caused by immaturity of type 2 alveolocytes and the resultant primary deficiency of puhnonary surthctant (PS) [2]. In RDS of adults, PS deficiency is secondary, developing as a result of structural and functional disorders in the airblood barrier. It often develops after multiple injury, sepsis, shock lung, radiation injury, etc. Natural and synthetic PS preparations have been widely used all over the world: smwana (USA), surfactant-TA (Japan), curosurf (Italy), alveofact (Germany), exosurf (UK) [8].We developed a technologically inexpensive method for preparing natural PS and chalacterized their physicochemical properties. Three preparations were studied: human PS isolated from parturients' amniotic fluid, PS from bronchoalveolar iavage fluid (PS-BLF), and PS prepared by water-salt extraction of finely dispersed cattle lung (PS-WSE).The pharmacological and therapeutic properties of these PS preparations are studied.

Surfactant Therapy for Patients with ARDS After Cardiac Surgery

“…Natural surfactant preparations with a composition close to that of the surfactant in situ are more efficient in animal models to improve gas exchange and in clinical practice Rosenberg et al, 2001). The biophysical and biochemical characteristics of Surfactant-BL are very similar to natural lung surfactant in situ (Rosenberg et al, 1998). Second, an early start of surfactant therapy may be important for the outcome of ARDS/ALI patients.…”

“…First, the surfactant preparation itself is an important determinant Rosenberg et al, 2001;Rosenberg et al, 1998;Taeusch et al, 2002). Natural surfactant preparations with a composition close to that of the surfactant in situ are more efficient in animal models to improve gas exchange and in clinical practice Rosenberg et al, 2001).…”

“…Bautin et al with organic solvents, which contains phospholipids, neutral lipids, and the surfactant-associated proteins SP-B and SP-C (Biosurf, Ltd., St. Petersburg, Russia); Surfactant-BL was approved for clinical use in newborns with RDS in Russia in 2000, and for adults with ARDS in 2003). The results of preclinical trials have been published earlier (Rosenberg et al, 1998).…”

Synthetic liposomes are protective from bleomycin-induced lung toxicity

“…Since a major component of lung surfactant is phosphatidylcholine, it is possible that liposomes may have been partly protective by reducing lung surface tension and/or by enhancing fluid clearance in response to bleomycin-induced alveolar edema (42). Because surfactant replacement therapy has been successful in the treatment of neonatal respiratory distress syndrome (1,8,14), it has been considered for the treatment of respiratory diseases in which lung surfactant deficiency or dysfunction also exist, such as acute lung injury or ARDS (2,3,11,13,20,26,27,32,38,44) and pulmonary fibrosis or IPF (17,40), but these applications have had minimal success.…”

“…Surfactant protein (SP)-A and -D are also critical components of innate pulmonary defense (24,43). Lung surfactant deficiency and/or dysfunction have been shown to exist in a number of pulmonary diseases such as neonatal respiratory distress syndrome (RDS) (1,8,14,37), acute lung injury from drugs or toxins (2,13,16,17,20,23,30,32,36,40), ARDS (3,10,11,26,27,38,44), and IPF (12,29). Lung surfactant therapy using protein-free natural animal-derived lung surfactant extracts or synthetic surfactants is a mainstay of current therapy for RDS in neonates (1,8,14) but has met with minimal success in the treatment of adult acute lung injury/ ARDS (3,11,26,44).…”