METHOD FOR IMPROVING BLADDER FUNCTION

Abstract

The invention pertains to the use of uridine and/or an equivalent thereof and n3-PUFA in the manufacture of a product for restoring or improving bladder function in a subject, in particular in a patient suffering from spinal cord injury.

Claims

1-13. (canceled)

14. A method for restoring or improving bladder function in a subject, comprising administering to the subject a composition comprising: (i) uridine and/or an equivalent thereof and (ii) n-3 PUFA.

15. The method according to claim 14, wherein the subject is suffering from, is recovering from and/or has suffered from a neurological disorder.

16. The method according to claim 15, wherein the neurological disorder is from spinal cord injury.

17. The method according to claim 14, wherein the n-3 PUFA is selected from EPA and/or DHA.

18. The method according to claim 17, wherein 500-5000 mg DHA is administered per day.

19. The method according to claim 14, wherein the composition further comprises choline.

20. The method according to claim 14, wherein the composition further comprises B vitamin(s).

21. The method according to claim 14, wherein the composition further comprises phospholipids, choline, B vitamin(s) and antioxidants.

22. The method according to claim 21, wherein the composition comprises choline, vitamin B6 and folic acid.

23. The method according to claim 14, wherein the uridine and/or equivalent thereof is uridine monophosphate.

24. The method according to claim 14, wherein the composition comprises per 125 mL or per daily dosage: (i) 400-800 mg UMP; (ii) n-3 PUFAs comprising (a) 100-500 mg EPA and (b) 900-1500 mg DHA; (iii) 50-600 mg phospholipids; (iv) 200-600 mg choline; (v) vitamins B comprising: (a) 1-5 g vitamin B12, (b) 0.5-3 mg vitamin B6 and (c) 200-600 g folic acid; and (vi) antioxidants comprising (a) 20-60 mg vitamin E (alpha-TE), (b) 60-100 mg vitamin C, and (c) 40-80 g selenium.

25. The method according to claim 14, wherein the composition is a liquid, or a solid which is reconstitutable with a liquid.

Description

EXAMPLES

Example 1

[0089] Female adult Sprague-Dawley rats (250g) were used in this project. The spinal cord of all animals was injured at thoracic level T12 (T12) using a static compression model (Nystrom et al., Acta Neurologica Scandinavica, 1998, 78, 460-6; Huang et al., European Journal of Neuroscience, 2007, 23, 273-8). After surgery, the rats were monitored regularly for any adverse effects, and weighed daily during the first two weeks post-injury, and then twice weekly thereafter. During the first week post-surgery, bladders were checked twice daily and were expressed manually when needed, and then once daily thereafter until the voiding reflex was re-established.

[0090] Rats were randomized to control and inventive diet groups before surgery. Rats in the control group received a regular AIN-93 M based rat chow (N=9), whereas rats in the inventive group were fed an inventive diet containing the same rat chow supplemented with a daily dose of 450 mg/kg (N=9) for 4 weeks. Both diets were isoenergetic and fulfilled all basic dietary requirements. They contained the standard vitamin mix (AIN-93-VX) and mineral mix (AIN-93-MX). The composition of the two diets differed with regard to the fat blends used, as well as a number of supplemented nutrients, included choline, B-vitamins, antioxidants, uridine monophosphate (UMP), and lecithin. The detailed composition of the diets is presented in Tables 1 and 2. To prevent lipid oxidation, all diets were stored at 20 C. until use. The diets were presented to the animals as hard pellets. All rats from both treatment groups received fresh diet pellets daily. Dietary treatment started immediately after recovery from surgery, once the rats were put back into their home cage, and a maximum of 4 rats were housed per cage. The amount of food eaten in each cage was monitored daily. Mean daily intakes were similar in all treatment groups.

TABLE-US-00001 TABLE 1 Diet composition (in g per 100 g of the composition) Control diet Inventive diet corn starch 35.6 31.3 casein (>85% protein) 14.0 14.0 corn dextrine 15.5 15.5 sucrose 10.0 10.0 dextrose 10.0 10.0 fibre 5.0 5.0 mineral mix (AIN-93M-MX) 3.5 3.5 vitamin mix (AIN-93-VX) 1.0 1.0 oil blend soy oil 1.9 0.0 coconut oil 0.9 0.1 corn oil 2.2 0.1 DHA25 oil (Nippon Suisan 0.0 4.5 Kaisha, LTD Tokyo, Japan) EPA 28/12 (Biosearch Life, 0.0 0.3 Granada, Spain) UMP disodium (24% H2O) 0.0 1.5 dl--tocopheryl acetate (500 IU/g) 0.0 0.705 Pyridoxine-HCL 0.0 0.0053 Folic acid (90%) 0.0 0.0011 Cyanocobalamin (0.1% in mannitol) 0.0 0.0065 Choline bitartrate 0.25 0.25 Choline chloride 0.0 0.67 Sodium selenite 0.0 0.00036 Tert-butylhydroquinone 0.0008 0.0008 L-cystine 0.18 0.18

TABLE-US-00002 TABLE 2 Fatty acid profile (in g per 100 g of the composition) Control diet Inventive diet C-18:1n9 1.041 0.656 C-18:2n6 (LA) 2.181 0.158 C-20:4n6 (AA) 0.00 0.092 C-18:3n3 (ALA) 0.107 0.038 C-20:5n3 (EPA) 0.00 0.433 C-22:6n3 (DHA) 0.00 1.117 total n-6 2.181 0.316 total n-3 0.107 1.663 n-3/n-6 0.049 5.265

[0091] Statistical tests were performed using GraphPad Prism version 6 (GraphPad Software Inc., San Diego, Calif., USA). Data sets were analyzed with Student's t tests or with two-way repeated-measures ANOVAs followed by post hoc analysis using the Bonferroni's post hoc comparisons test, where appropriate. All data are given as meanS.E.M. P<0.05 was considered statistically significant.

[0092] Comparison of the group of rats that were fed the inventive diet with that that were fed the standard maintenance diet showed that the ability for bladder voiding recovered significantly quicker in the rats treated with the inventive diet (days to bladder recovery (control diet)=8.81.8; (inventive diet)=3.91.1, P<0.05). In the inventive diet group, four rats out of seven had already recovered full control of their bladder by post-surgery day 2, and all rats had recovered bladder function by day 8. In the control group, only two rats out of 6 had recovered bladder voiding by post-surgery day 10, and all rats had recovered bladder function by day 12.

Example 2

[0093] A liquid composition according to the invention, comprising per 125 mL serving:

TABLE-US-00003 4.9 g fat 40 mg vitamin E (alpha-TE) 300 mg EPA 80 mg vitamin C 1200 mg DHA 60 g selenium 106 mg phospholipids 3 g vitamin B12 400 mg choline 1 mg vitamin B6 625 mg UMP 400 g folic acid