Drug – bio-affecting and body treating compositions – Extract – body fluid – or cellular material of undetermined... – Respiratory system
Reexamination Certificate
1998-08-21
2001-01-30
Saucier, Sandra E. (Department: 1651)
Drug, bio-affecting and body treating compositions
Extract, body fluid, or cellular material of undetermined...
Respiratory system
C514S078000
Reexamination Certificate
active
06180142
ABSTRACT:
BACKGROUND OF THE INVENTION
1. Field of the Invention
This invention resides in the fields of respiratory distress syndrome, pre-natal and neonatal infant care in general, and lung diseases of both infants and adults. In particular, this invention addresses issues related to the use of naturally-occurring surfactants, modifications of natural surfactants, and synthetic analogs of natural surfactants as therapeutic agents for the treatment of various conditions.
2. Description of the Prior Art
Acute lung injury is a major clinical problem that includes diseases as disparate as acute respiratory distress syndrome in adults, neonatal respiratory distress syndrome, meconium aspiration pneumonia in newborn infants, bacterial and viral pneumonia, pneumonia caused by aspiration of stomach contents, smoke inhalation, and near drowning. Respiratory distress syndrome, for example, is a common disorder in premature infants, and interest in this disorder among pediatricians and pathologists has grown since the 1940s. Within the last twenty years, however, the use of exogenous pulmonary surfactants has emerged as an effective therapy for the treatment and prevention of this disorder. The use of pulmonary surfactants was first reported by Fujiwara and coworkers in 1980 whose studies showed the successful reduction of respiratory distress in preterm infants by the instillation of bovine lung surfactant into the trachea of the infants. Subsequent work by Fujiwara and others has led to the use of a variety of mammalian-derived lung surfactants as therapeutic agents, particularly surfactants that have been extracted, supplemented or otherwise treated to improve their effectiveness. With these advances in surfactant therapy, neonatal deaths and various related lung diseases no longer have the high morbidity rates that they once had.
Unfortunately, a significant percentage of cases fail to respond adequately to surfactant therapy, experiencing instead only a transitory or minimal response. Numerous explanations for this have been offered, each citing the inactivation of surfactant in situ by one or more substances that are normally absent from the alveolar spaces. Aside from the inactivation of exogenous surfactants, endogenous surfactants can be inactivated as well, and this has been implicated as the cause or one of the contributing factors or symptoms of several of the various disease conditions listed in the preceding paragraph. In either case, the substances suspected of causing inactivation include blood, plasma proteins, serum proteins, lipids, and meconium, which is the mass of mucous, desquamated epithelial cells, lanugo, and vernix caseosa that collects in the fetal intestine.
In some cases, inactivation of surfactant, whether exogenous or endogenous, has been reduced by increasing the amount of surfactant relative to the inactivating substance.
Inactivation has also been reduced by the administration or co-administration of the surfactant-associated proteins SP-A, SP-B, and SP-C. These proteins are not readily available, however, since they must either be extracted from naturally-occurring surfactants or synthesized by protein synthesis techniques. Accordingly, the search for substances that are effective in countering the various forms of inactivation continues.
SUMMARY OF THE INVENTION
It has now been discovered that one can reduce or eliminate the inactivation of exogenous therapeutic pulmonary surfactants by administering nonionic hydrophilic polymers or carbohydrates in conjunction with the surfactants. Thus, a composition containing as active ingredients (a) a surfactant that is effective in the abatement of pulmonary disorders and (b) either a biocompatible nonionic hydrophilic polymer or a biocompatible carbohydrate is discovered to be an effective therapeutic agent for the treatment of such disorders, in many cases to a degree that is unexpectedly greater than that achieved with administration of the surfactant alone. The invention thus extends to such combinations as novel compositions of matter as well as to the administration of such combinations as novel means of treating, reducing or preventing of such disorders.
An extension of this discovery is the usefulness of the nonionic hydrophilic polymers and carbohydrates, either by themselves or in combination with exogenous pulmonary surfactants to remove thick secretions from the airway in respiratory conditions such as cystic fibrosis, asthma, bronchiectasis, and bacterial pneumonia, and for patients who are at risk of tube blockage while being maintained on assisted ventilation.
A further extension of this discovery is the usefulness of the nonionic hydrophilic polymers and carbohydrates in solubilizing meconium, whose presence is responsible for various cases of pulmonary surfactant inactivation. In this regard, the invention provides a means for ravaging the uterus by infusion with an aqueous solution of the nonionic hydrophilic polymer or carbohydrate, with or without surfactant. The invention is thus useful in reducing abnormally high meconium concentrations in the amniotic fluid or correcting conditions arising from an abnormal reduction in the volume of amniotic fluid.
The usefulness of the nonionic hydrophilic polymers and carbohydrates in removing thick airway secretions and in solubilizing meconium extends the utility of these compounds beyond that of enhancing the effectiveness of a surfactant and is independent of the presence or absence of surfactant. The invention thus finds utility in the treatment of a wide range of conditions, including those which respond to pulmonary surfactant treatment as well as those in which excessive or highly concentrated meconium or other pulmonary secretions poses a threat to the health and safety of fetuses, children and adults alike.
Other aspects, objects, features, and advantages of the invention will become apparent from the description that follows.
REFERENCES:
patent: 4312860 (1982-01-01), Clements
patent: 4826821 (1989-05-01), Clements
patent: 5108759 (1992-04-01), Ranney
patent: 5110806 (1992-05-01), Clements
patent: 5855913 (1999-01-01), Hanes et al.
patent: 5885974 (1999-03-01), Danielov
patent: WO 96/19197 (1996-06-01), None
patent: WO 97/35882 (1997-10-01), None
patent: WO 99/09955 (1999-03-01), None
Galan et al. Obstetrics and Genecology, Oct. 1992, vol. 80, No. 4, pp. 604-608.
Van Oss et al. Separation Science and Technology, 1987, 22(6), pp. 1515-1526.
H.W. Taeusch,Surfactant Therapy for Lung Disease(1995) Marcel Dekker, Inc., New York.
Afremova Vera
Saucier Sandra E.
The Regents of the University of California
Townsend and Townsend / and Crew LLP
LandOfFree
Reduction of surfactant inactivation in pulmonary surfactant... does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Reduction of surfactant inactivation in pulmonary surfactant..., we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Reduction of surfactant inactivation in pulmonary surfactant... will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-2536056