New use of ammonium compounds and/or urea

Abstract

The use of a physiologically innocuous ammonium compound and/or urea as an additive to an infant formula or a pap or for the preparation of a pharmaceutical composition for the prophylaxis of sudden infant death syndrome (SIDS) is disclosed as is also, an infant formula or a pap which in addition to conventional ingredients contains a physiologically innocuous ammonium compound an/or urea. Furthermore, a method of preventing SIDS is disclosed, which method comprises administering to the infant an infant formula or a pap as indicated above, and a method for prophylaxis of SIDS, wherein a pharmaceutical composition containing a physiologically innocuous ammonium compound and/or urea is administered to the infant or the appropriately selected or modified non-pathogenic, urease-producing bacteria are supplied to the gastrointestinal tract of the infant. Finally, a method for the diagnosis of the risks for SIDS is disclosed according to which method the faeces of the infant are analyzed with respect to the presence of urea, urease activity and/or ammonium ions, the presence of urea, the absence of abnormally low urease activity and ammonium ion, respectively, indicating risks for SIDS.

Description

ANNEX INCLUDING CLEAN VERSION OF AMENDED SPECIFICATION

[0001] Please replace the paragraph beginning at line 5 on page 2 with the following: In order that an animal or a human being should be able to live it is required that its body functions are regulated in such a way that there is an acid-base balance. Expressed in another way: A normal pH-value must exist in the cells, in the extracellular liquid and in the cell organelles. If this is not the case first slight functional disorders, then even increasing diseases and finally death of structures, cells and the whole organism occurs. For instance, it is known that the mortality in several diseases increases when the pH value of the extracellular liquid (normally 7.40) is above 7.55 or below 7.20.

[0002] Please replace the paragraph beginning at line 17 on page 2 with the following: Under the latest decades the opinion of the acid-base balance has not changed materially. During the 1980's, however, Atkinson and co-workers [Atkinson D E et al, Curr Top Cell Regul, 21, 261-302 (1982)] again called attention to the previously known, but among physiologists and medical physicians not accepted fact that the metabolism of mammals not only produced the main metabolites carbon dioxide, water and urea but also hydrogen carbonate. His theory also meant that the metabolism by producing hydrogen carbonate above all via amino acid metabolism in order to result in the metabolic end products carbon dioxide and water must be supplied with protons and that this process for quantitative reasons had to occur via the omithine cycle. One of the objections against this theory has been that if such an important life process does not function the animal or the human being in question should rapidly die. However, no such lacking function of the system proposed by Atkinson has even been pointed out and even less been proven which constitutes one of the deficiencies of his theory.

[0003] Please replace the paragraph beginning at line 1 on page 5 with the following: portal area, especially at acidosis, can be utilized for synthesis of glutamine in the liver. It is also known by intensive care physicians that ammonium chloride supplied intravenously and perorally lowers base excess values and such supply is accordingly used as a matter of routine for the treatment of a metabolic alkalosis. When the patient treated is breathing by himself, the supply of ammonium will bring about a so-called compensatory hyperventilation. The present inventor has administered himself 80 mmoles ammonium chloride perorally and thereby has been able to establish that this substance obviously is resorbed very quickly from the gastrointestinal tract and causes a slight hyperventilation which in turn causes an increase in RQ (“Respiratory Quotient”=the quotient between the carbon dioxide emission and the oxygen gas uptake in a person—in both cases expressed in ml/min) from a value at rest of 0.82 to 0.87 and the elimination of carbon dioxide increases by 30 ml/min and that this seems to proceed for nearly 1h, which corresponds to about 80 mmoles of carbon dioxide. Furthermore, there is a report on the concentration of urea in the vitreous body of dead SIDS patients which is compared to autopsy material from children deceased from other causes at the same age [Blumenfeld T A, et al, Am J Clin Pathol, 71, 219-223 (1979)]. It appeared that children deceased from SIDS have lower urea values than children deceased from other causes. As a normal enterohepatic circulation of urea and ammonium ion hypothetically does not function in these cases this should have the consequence that the production of urea is less than normally and since the volume of distribution is equal this means that the concentration in various body fluids decreases. The low concentration of urea found is thus not inconsistent with the hypothesis put forward here.

Claims

11. An infant formula comprising an effective amount of ammonium chloride as an additive to said infant formula, wherein said effective amount of ammonium chloride is sufficient to reduce the risk of sudden infant death syndrome (SIDS) in infants.

12. The infant formula of claim 11, wherein the ammonium chloride is present at a concentration of 0.2-0.6 mmol/l in an infant formula ready for administration to an infant during the first month of life.

13. The infant formula of claim 11, wherein the ammonium chloride is present at a concentration of 0.1-5 mmol/l in an infant formula ready for administration to an infant during months 2-7 of life.

14. The infant formula of claim 11, which is in the form of a powder.

15. The infant formula of claim 12, wherein the concentration of the ammonium chloride is 0.5 mmol/l.

16. The infant formula of claim 12, wherein the concentration of the ammonium chloride is 0.5-2 mmol/l.

17. A method of reducing the risk of sudden infant death syndrome (SIDS) in infants comprising administering an infant formula or pap composition comprising an effective amount of ammonium chloride, urea or a mixture thereof, wherein said effective amount of ammonium chloride, urea or mixture thereof is sufficient to reduce the risk of SIDS in infants.

18. The method of claim 17, wherein the infant formula or pap composition is administered to an infant during the first month of life, and the concentration of ammonium chloride in the infant formula or pap composition is 0.2-0.6 mmol/l.

19. The method of claim 17, wherein the infant formula or pap composition is administered to an infant during months 2-7 of life, and the concentration of ammonium chloride in the infant formula or pap composition is 0.1-5 mmol/l.

20. The method of claim 17, wherein the infant formula or pap composition is administered to an infant during the first month of life, and the concentration of urea in the infant formula or pap composition is 1-5 mmol/l.

21. The method of claim 17, wherein the infant formula or pap composition is administered to an infant during months 2-7 of life, and the concentration of urea in the infant formula or pap composition is 1-10 mmol/l.

22. A method for the prophylaxis of sudden infant death syndrome (SIDS) in infants comprising administering an infant formula or pap composition comprising an effective amount of ammonium chloride, urea or mixture thereof wherein said effective amount of ammonium chloride, urea or mixture thereof is sufficient for prophylaxis of SIDS in infants.

23. The method of claim 22, wherein the infant formula or pap composition is administered to an infant during the first month of life, and the concentration of ammonium chloride in the infant formula or pap composition is 0.2-0.6 mmol/l.

24. The method of claim 22, wherein the infant formula or pap composition is administered to an infant during months 2-7 of life, and the concentration of ammonium chloride in the infant formula or pap composition is 0.1-5 mmol/l.

25. The method of claim 22, wherein the infant formula or pap composition is administered to an infant during the first month of life, and the concentration of urea in the infant formula or pap composition is 1-5 mmol/l.

26. The method of claim 22, wherein the infant formula or pap composition is administered to an infant during months 2-7 of life, and the concentration of urea in the infant formula or pap composition is 1-10 mmol/l.

27. A pap composition comprising an effective amount of ammonium chloride as an additive to said pap composition, wherein said effective amount of ammonium chloride is sufficient to reduce the risk of sudden infant death syndrome in infants.

28. The pap composition of claim 27, wherein the ammonium chloride is present at a concentration of 0.1-5 mmol/l in an infant formula ready for administration to an infant during months 2-7 of life.

29. The pap composition of claim 27, which is in the form of a powder.

30. The pap composition of claim 28, wherein the concentration of the ammonium chloride is 0.5 mmol/l.

31. The pap composition of claim 28, wherein the concentration of the ammonium chloride is 0.5-2 mmol/l.