U.S. patent application number 12/064686 was filed with the patent office on 2009-09-03 for nutrition for obese patients.
This patent application is currently assigned to NESTEC S.A.. Invention is credited to Claudia Roessle.
Application Number | 20090220637 12/064686 |
Document ID | / |
Family ID | 37735137 |
Filed Date | 2009-09-03 |
United States Patent
Application |
20090220637 |
Kind Code |
A1 |
Roessle; Claudia |
September 3, 2009 |
NUTRITION FOR OBESE PATIENTS
Abstract
This invention provides a composition and method for providing
nutritional support to obese patients. The composition has an
energy density between 0.4 and 0.9 kcal/ml and comprises a protein
source which comprises at least 30% by weight whey protein and
provides at least 30% of the total calories of the composition. The
composition may include a carbohydrate source and a lipid source.
Preferably, at least 50% by weight of the protein source is whey
protein. The invention further extends to use of the composition in
the prevention or treatment of malnutrition in obese patients.
Inventors: |
Roessle; Claudia; (Morges,
CH) |
Correspondence
Address: |
Nestle HealthCare Nutrition
12 Vreeland Road, 2nd Floor, Box 697
Florham Park
NJ
07932
US
|
Assignee: |
NESTEC S.A.
|
Family ID: |
37735137 |
Appl. No.: |
12/064686 |
Filed: |
August 22, 2006 |
PCT Filed: |
August 22, 2006 |
PCT NO: |
PCT/EP06/65562 |
371 Date: |
June 30, 2008 |
Current U.S.
Class: |
426/2 ;
426/73 |
Current CPC
Class: |
A23L 33/15 20160801;
A61P 19/02 20180101; A61P 3/10 20180101; A61P 9/10 20180101; A61P
3/04 20180101; A61P 3/06 20180101; A61P 9/12 20180101; A61P 11/00
20180101; A23L 33/30 20160801; A61P 3/02 20180101; A23L 33/40
20160801; A23L 33/19 20160801; A23L 33/16 20160801; A23V 2002/00
20130101; A61P 1/16 20180101; A23V 2002/00 20130101; A23V 2200/332
20130101; A23V 2250/54252 20130101; A23V 2250/54 20130101; A23V
2250/702 20130101; A23V 2250/708 20130101; A23V 2250/712 20130101;
A23V 2250/1642 20130101; A23V 2250/1626 20130101 |
Class at
Publication: |
426/2 ;
426/73 |
International
Class: |
A23K 1/18 20060101
A23K001/18; A23L 1/303 20060101 A23L001/303 |
Foreign Application Data
Date |
Code |
Application Number |
Aug 26, 2005 |
EP |
05018626.1 |
Nov 9, 2005 |
EP |
05110556.7 |
Claims
1. Use of a protein source, Vitamin A, Vitamin C, Vitamin E, zinc
and selenium in the manufacture of a composition for the prevention
or treatment of malnutrition in an obese patient wherein the
composition has an energy density between 0.4 and 0.9 kcal/ml and
comprises per litre at least 500 .mu.g RE of Vitamin A, 70 mg of
Vitamin C, 9.0 mg .alpha. TE of Vitamin E, 4.0 mg zinc and 30 mg
selenium and the protein source comprises at least 30% by weight
whey protein and provides at least 30% of the total calories of the
composition.
2. Use of a protein source, a carbohydrate source and a lipid
source in the manufacture of a composition for the prevention or
treatment of malnutrition in an obese patient wherein the
composition has an energy density between 0.4 and 0.9 kcal/ml and
the protein source provides comprises at least 30% by weight whey
protein and at least 30% of the total calories of the
composition.
3. The use of claim 1 or 2 wherein the composition comprises per
litre at least 1000 .mu.g RE of Vitamin A, 125 mg of Vitamin C,
15.0 mg .alpha. TE of Vitamin E, 10.0 mg zinc and 100 mg
selenium.
4. The use of any preceding claim wherein at least 50% by weight of
the protein source is whey protein.
5. The use of any preceding claim, wherein whey protein constitutes
between 60 and 85% by weight of the protein source.
6. The use of any preceding claim, wherein the protein source
provides from 40 to 50% of the total calories of the
composition.
7. The use of any preceding claim, wherein the composition further
comprises from 10 to 40 g/l of dietary fibre.
8. The use of any of claims 2 to 7, wherein the carbohydrate source
provides from 25 to 45% of the total calories of the
composition.
9. The use of any of claims 2 to 8, wherein the lipid source
provides from 25 to 30% of the total calories of the
composition.
10. The use of any of claims 2 to 9, wherein the ratio of n6:n3
long chain polyunsaturated fatty acids in the lipid source is
between 6:1 and 2:1.
11. A nutritional composition for the prevention or treatment of
malnutrition in an obese patient which composition has an energy
density between 0.4 and 0.9 kcal/ml and comprises at least 500
.mu.g RE of Vitamin A, 70 mg of Vitamin C, 9.0 mg .alpha. TE of
Vitamin E, 4.0 mg zinc and 30 mg selenium and a protein source
which provides at least 30% of the total calories of the
composition, wherein at least 30% by weight of the protein source
is whey protein.
12. A nutritional composition for the prevention or treatment of
malnutrition in an obese patient which composition has an energy
density between 0.4 and 0.9 kcal/ml and comprises a protein source
which provides at least 30% of the total calories of the
composition, a carbohydrate source and a lipid source wherein at
least 30% by weight of the protein source is whey protein.
13. The composition of claim 11 or 12 wherein at least 50% by
weight of the protein source is whey protein.
14. The composition of any of claims 11 to 13, wherein whey protein
constitutes between 60 and 85% by weight of the protein source.
15. The composition of any of claims 11 to 14, wherein the protein
source provides from 40 to 50% of the total calories of the
composition.
16. The composition of any of claims 11 to 15 wherein the
composition further comprises from 10 to 40 g/l of dietary
fibre
17. The composition of any of claims 12 to 16, wherein the
carbohydrate source provides from 25 to 45% of the total calories
of the composition.
18. The composition of any of claims 12 to 17, wherein the lipid
source provides from 25 to 30% of the total calories of the
composition.
19. The composition of any of claims 12 to 18, wherein the ratio of
n6:n3 long chain polyunsaturated fatty acids in the lipid source is
between 6:1 and 2:1.
20. The composition of any of claims 11 to 19, wherein the
composition further comprises per litre at least 1000 .mu.g RE of
Vitamin A, at least 125 mg of Vitamin C, at least 15.0 mg .alpha.
TE of Vitamin E, at least 10.0 mg zinc and at least 100 mg
selenium.
Description
[0001] This invention relates generally to compositions and methods
for the treatment and nutritional support of patients. More
specifically, this invention relates to the nutritional support of
obese patients prior to, during and after hospitalisation for
surgery, treatment of diseases or other disorders as well as during
periods of convalescence.
[0002] The prevalence of obesity in adults, children and
adolescents has increased rapidly over the past 30 years in the
United States and globally and continues to rise. Obesity is
classically defined based on the percentage of body fat or, more
recently, the body mass index or BMI. The BMI is defined as the
ratio of weight in Kg divided by the height in metres, squared. As
obesity becomes more prevalent in all age groups, it is inevitable
that the number of patients in hospitals who are also obese will
increase.
[0003] Many obese patients have pre-existing chronic diseases
related to their obesity such as impaired glycaemic control,
diabetes mellitus, coronary artery disease, hypertension,
respiratory abnormalities, hyperlipidaemia, degenerative joint
disease, and hepatobiliary disease that are likely to complicate
even routine hospital care. In addition, obese patients are more
likely than their non-obese counterparts to develop postoperative
complications such as impaired wound-healing, nosocomial
infections, respiratory complications, and delayed cardiac
recuperation. In adult intensive care patients, obesity (BMI
greater than 30) has even been reported to be significantly
associated with increased risk of mortality. Obesity entails
increased oxidative stress and, in many cases, sarcopenia. It is
well known that acute illness and/or surgical intervention is also
associated with oxidative stress as well as negative nitrogen
balance and loss of muscle mass, and in many cases insulin
resistance is enhanced. In other words, acute illness is likely to
exacerbate physiological and metabolic alterations already present
at baseline in obese patients.
[0004] Recently, Dickerson et al (Nutrition 18:241-246 2002)
compared the effects of hypocaloric and eucaloric enteral tube
feeding in critically ill obese patients. Their results suggested
that hypocaloric enteral nutritional support (by which the authors
meant feeding a composition with an energy density of at least 1.0
kcal/ml) was at least as effective as eucaloric feeding in this
group. In the more generalised group of obese patients who,
although ill, are not critically ill, there is a tendency for the
nutrition offered post operatively in particular to be less than
ideal. These patients tend to be offered either the same feeds as
non-obese patients and thus ingest calories they do not require.
Alternatively, it is assumed that in the short term no nutritional
support at all is needed because the patients are calorically
abundant. However, this overlooks the possibility that, when
stressed for example by illness or surgery, obese patients may
suffer from protein and micronutrient depletion just as non-obese
patients do. Further, as noted above, obese patients are at greater
risk of postoperative complications and would be in better
conditions to resist these complications if they were not further
weakened by impaired nutritional status. A need therefore exists
for a nutritional composition designed to meet the nutritional
needs of patients who are obese.
SUMMARY OF THE INVENTION
[0005] In a first aspect, this invention provides the use of a
protein source, Vitamin A, Vitamin C, Vitamin E, zinc and selenium
in the manufacture of a composition for the prevention or treatment
of malnutrition in an obese patient wherein the composition has an
energy density between 0.4 and 0.9 kcal/ml and comprises per litre
at least 500 .mu.g RE of Vitamin A, 70 mg of Vitamin C, 9.0 mg
.alpha. TE of Vitamin E, 4.0 mg zinc and 30 mg selenium and the
protein source comprises at least 30% by weight whey protein and
provides at least 30% of the total calories of the composition.
[0006] In a second aspect, this invention provides a nutritional
composition for the prevention or treatment of malnutrition in an
obese patient which composition has an energy density between 0.4
and 0.9 kcal/ml and comprises per litre at least 500 .mu.g RE of
Vitamin A, 70 mg of Vitamin C, 9.0 mg .alpha. TE of Vitamin E, 4.0
mg zinc and 30 mg selenium and a protein source which provides at
least 30% of the total calories of the composition wherein at least
30% by weight of the protein source is whey protein.
[0007] In a third aspect, this invention provides the use of a
protein source, a carbohydrate source, and a lipid source in the
manufacture of a composition for the prevention or treatment of
malnutrition in an obese patient wherein the composition has an
energy density between 0.4 and 0.9 kcal/ml and the protein source
comprises at least 30% by weight whey protein and provides at least
30% of the total calories of the composition.
[0008] In a fourth aspect, this invention provides a nutritional
composition for the prevention or treatment of malnutrition in an
obese patient which composition has an energy density between 0.4
and 0.9 kcal/ml and comprises a protein source which provides at
least 30% of the total calories of the composition, a carbohydrate
source and a lipid source wherein at least 30% by weight of the
protein source is whey protein.
[0009] In a fifth aspect, this invention provides a method of
preventing or treating malnutrition in an obese patient in need
thereof by administering a therapeutic amount of a nutritional
composition comprising a protein source wherein the composition has
an energy density between 0.4 and 0.9 kcal/ml and the protein
source comprises at least 30% by weight of whey protein and
provides at least 30% of the total calories of the composition.
[0010] Preferably whey protein constitutes at least 50% of the
protein source, more preferably from 60 to 85% of the protein
source.
[0011] In the event that the nutritional composition comprises a
source of carbohydrates and a source of lipids, the protein source
may provide 30 to 65% of the total calories of the composition,
preferably from 35 to 50% and more preferably 40 to 50% of the
total calories of the composition.
[0012] The composition may be a nutritional supplement, that is,
nutritionally incomplete and intended to be consumed in addition to
other foodstuffs or it may be nutritionally complete, including a
carbohydrate source and a lipid source in addition to the protein
source. It may be formulated as a ready to consume liquid for sip
feeding or tube feeding, as a powdered composition which may be
reconstituted with water prior to being fed orally or administered
by tube feeding, as a semi-liquid food such as a spoonable dessert
or in any other appropriate form e.g. bars, biscuits etc.
[0013] If present, the carbohydrate source may provide 20 to 50% of
the total calories of the composition and preferably from 25 to 45%
of the total calories of the composition.
[0014] If present, the lipid source may provide 10 to 40% of the
total calories of the composition and preferably from 25 to 30% of
the total calories of the composition.
DETAILED DESCRIPTION OF THE INVENTION
[0015] In this specification, the term "obese patient" means an
individual who is obese i.e. with a BMI greater than 30 and who is
undergoing or requires or is convalescing from therapy or surgery
for a related or unrelated condition. Examples of "related
conditions" include conditions that are thought to be linked with
overweight and obesity such as development of metabolic syndrome
and Type II diabetes.
[0016] References to components of the composition being present in
a specified number of grams per litre refer in the context of
powdered compositions to the composition after re-constitution.
[0017] Whey protein comprises at least 30% of the protein source in
the composition of the invention, preferably at least 50% and more
preferably from 60 to 85% of the protein source. Whey protein has
fast gastric emptying and is associated with an increased satiety
response so is suitable for a hypocaloric composition for obese
patients. Further, it has been shown to stimulate insulin release
in healthy subjects as well as those suffering from Type II
diabetes and is thus a suitable protein source for individuals who
may suffer from impaired glycaemic control. Whey protein has also
been demonstrated to stimulate postprandial protein accretion; in
particular in elderly subjects suggesting that protein losses can
be limited by intake of whey protein. It is also a rich source of
branched-chain amino acids which it is believed may be associated
with the stimulation of protein synthesis. Further, whey protein is
a rich source of cysteine which is a key constituent of
glutathione, a major endogenous antioxidant. It has been shown that
cysteine and glutathione are depleted in critically ill patients
and that supplementation with cysteine can attenuate this
depletion. Finally, whey protein is believed to have
anti-inflammatory properties which may be of relevance in the
treatment of conditions such as obesity which are thought to
engender chronic low-level inflammation. The whey protein may be
intact or partially or extensively hydrolysed. Mixtures of intact
and hydrolysed whey proteins may be used.
[0018] The balance of the protein source may be any suitable
protein such as defatted milk protein, soy protein or casein, in
each case either in the intact form or hydrolysed. Mixtures of the
above proteins may also be used as may mixtures of intact and
hydrolysed proteins. Free amino acids such as Leucine may also be
added.
[0019] The lipid source if present preferably does not contribute
more than 40% of the total calories of the composition since the
use of endogenous lipid stores should be stimulated in obese
patients. Nevertheless, essential fatty acid intake should be
considered.
[0020] A high intake of n-6 polyunsaturated fats should preferably
be avoided where there is a risk of stress and inflammatory
conditions. Preferably, the ratio of n6/n3 fatty acids should be
between 2:1 and 6:1. These requirements can, for example, be met by
using a blend of canola oil, corn oil and high-oleic acid sunflower
oil supplemented with a source rich in n3 PUFA such as fish oil if
a higher n3 content is required. The lipid source may also include
medium chain triglycerides if required.
[0021] The nutritional composition of the present invention may
contain a carbohydrate source. Preferably, the carbohydrate source
should be slowly digested or metabolised independently of insulin,
thus avoiding high post-prandial glycaemic peaks. Suitable
carbohydrate sources are modified starches such as modified potato
or tapioca starch, dextrins such as tapioca dextrin, isomaltulose,
trehalose, tagatose, fructose and polyols such as xylitol and
sorbitol as well as mixtures thereof. The composition may also
contain minerals, micronutrients and trace elements in accordance
with the recommendations of Government bodies such as the USRDA.
Preferably the composition contains elevated amounts of Vitamins A,
C, and E, zinc and selenium, for example, per litre at least: 500
.mu.g RE of Vitamin A, 70 mg of Vitamin C, 9.0 mg .alpha. TE of
Vitamin E, 4.0 mg zinc and 30 mg selenium, more preferably per
litre at least: 1000 .mu.g RE of Vitamin A, 125 mg of Vitamin C,
15.0 mg .alpha. TE of Vitamin E, 10.0 mg zinc and 100 mg
selenium.
[0022] The composition preferably also contains elevated amounts of
iron, calcium, folate, Vitamin B12, Vitamin D and Vitamin K, for
example, per litre at least 6 mg iron, 500 mg calcium, 160 mg
folate, 2.0 .mu.g Vitamin B12, 8 .about.g Vitamin D and 60 .mu.g
Vitamin K.
[0023] The composition may further contain a source of dietary
fibre. Dietary fibre passes through the small intestine undigested
by enzymes and functions as a natural bulking agent and laxative.
Dietary fibre may be soluble or insoluble and in general a blend of
the two types is preferred. Suitable sources of dietary fibre
include soy, oat and gum Arabic and mixtures thereof. A
particularly preferred fibre blend is a mixture of outer pea fibre
(predominantly insoluble), inner pea fibre, acacia gum and short
chain fructo-oligosaccharides (all soluble). Preferably, if fibre
is present the fibre content is between 10 and 40 g/l.
[0024] The composition may be manufactured in any suitable manner.
For example, the composition may be manufactured by blending
together the protein source, the carbohydrate source (if present),
and the lipid source (if present) in appropriate proportions. If
used, emulsifiers may be included in the blend at this stage. The
vitamins and minerals may be added at this point but are usually
added later to avoid thermal degradation. Any lipophilic vitamins,
emulsifiers and the like may be dissolved into the lipid source
prior to blending. Water, preferably water which has been subjected
to reverse osmosis, may then be mixed in to form a liquid
mixture.
[0025] The liquid mixture may then be thermally treated to reduce
bacterial loads. For example, the liquid mixture may be rapidly
heated to a temperature in the range of about 80.degree. C. to
about 110.degree. C. for about 5 seconds to about 5 minutes. This
may be carried out by steam injection or by heat exchanger; for
example a plate heat exchanger.
[0026] The liquid mixture may then be cooled to about 60.degree. C.
to about 85.degree. C.; for example by flash cooling. The liquid
mixture may then be homogenised; for example in two stages at about
7 MPa to about 40 MPa in the first stage and about 2 MPa to about
14 MPa in the second stage. The homogenised mixture may then be
further cooled and any heat sensitive components; such as vitamins
and minerals may be added. The pH and solids content of the
homogenised mixture is conveniently standardised at this point.
[0027] If it is desired to produce a powdered composition, the
homogenised mixture is transferred to a suitable drying apparatus
such as a spray drier or freeze drier and converted to powder. The
powder should have a moisture content of less than about 5% by
weight.
[0028] If it is desired to produce a liquid composition, the
homogenised mixture is filled into suitable containers; preferably
aseptically. However, the composition may also be retorted in the
container. Suitable apparatus for carrying out filling of this
nature is commercially available. The composition may be in the
form of a ready to feed product having a solids content of about 10
to about 14% by weight or may be in the form of a concentrate;
usually of solids content of about 20 to about 26% by weight.
[0029] Alternatively, to prepare a liquid composition based on
intact whey proteins, whey protein isolate may be dissolved in
demineralised water. After complete dissolution of the protein, the
carbohydrate is added to the protein solution. After complete
dissolution of the carbohydrate, the pH is adjusted to 3.0 at
ambient temperature. The resulting solution is heat sterilised
(e.g. UHT), cooled and the pH is adjusted to 6.8 under aseptic
conditions.
[0030] Meanwhile, a dispersion of defatted milk protein concentrate
and tri-calcium-citrate in demineralised water is prepared. The fat
mix is warmed to 70.degree. C. and mono-diglycerides are dissolved
in the fat. The fat mix is emulsified together with the protein
dispersion using a colloidal mill. The resulting coarse emulsion is
homogenised at 200 bar/40 bar at ca 65.degree. C. The minerals,
trace elements and vitamins are then added to the emulsion and its
pH is adjusted to 6.8. The resulting emulsion is UHT sterilised,
flash-cooled to 70.degree. C. and then aseptically homogenised. The
emulsion is cooled to about 10.degree. C. and pumped to a sterile
tank where it is mixed with the protein/carbohydrate phase After
thorough mixing in the tank, the sterile composition is filled
aseptically into the desired containers.
EXAMPLE 1
[0031] Two examples of complete nutritional compositions for sip
feeding according to the present invention are given below. The
compositions are given by way of illustration only.
[0032] The compositions include the following ingredients: protein:
whey protein (50% by weight of total protein), defatted milk
protein; carbohydrate: modified tapioca and corn starch; fat: about
50% canola oil, about 20% corn oil, about 30% high-oleic sunflower
oil, n6:n3 ratio about 5; fibre (inner pea fibre, outer pea fibre
and fructo-oligosaccharides); water; vitamin A; vitamin C vitamin
D; vitamin E; vitamin K; vitamin B.sub.1; Vitamin B.sub.2; vitamin
B.sub.6; niacin; folic acid; pantothenic acid; vitamin B.sub.12;
biotin; calcium; magnesium; zinc; iron; copper; manganese; iodine;
sodium; potassium; chloride; chromium; molybdenum; fluoride and
selenium.
[0033] The compositions have the following nutrient profiles (per
200 ml serving):
TABLE-US-00001 Nutrient Composition Example A Example B Caloric
Density 0.5 kcal/ml 0.75 kcal/ml Protein (g) 12 15 Carbohydrate (g)
6.8 11.25 Fat (g) 2.8 5 Dietary Fibre (g) 5.2 5.2 Vitamin A (.mu.g
RE) 210 210 E Vitamin D (.mu.g) 2.6 2.6 Vitamin E (mg .alpha. TE)
3.2 4.5 E Vitamin K (.mu.g) 13.8 13.8 Vitamin C (mg) 26 26 Vitamin
B1 (mg) 0.3 0.3 Vitamin B2 (mg) 0.36 0.36 Niacin (mg) 3.0 3.0
Vitamin B6 (mg) 0.42 0.42 Folic Acid (.mu.g) 60 60 Pantothenic Acid
(mg) 1.2 1.2 Vitamin B12 (.mu.g) 0.7 1.0 Biotin (.mu.g) 7.5 12
Calcium (mg) 240 240 Magnesium (mg) 40 40 Zinc (mg) 2.4 2.4 Iron
(mg) 2.0 2.0 Copper (mg) 0.24 0.24 Manganese (mg) 0.5 0.5 Iodine
(.mu.g) 20 20 Sodium (mg) 70 70 Potassium (mg) 260 260 Chloride
(mg) 140 140 Chromium (.mu.g) 12.4 12.4 Molybdenum (.mu.g) 15 15
Selenium (.mu.g) 12.6 12.6 Fluoride (mg) 0.2 0.2
EXAMPLE 2
[0034] Two examples of liquid tube feeding compositions according
to the present invention are given below. The compositions are
given by way of illustration only.
[0035] The compositions include the following ingredients: protein:
hydrolysed whey protein (50% by weight of total protein), potassium
caseinate; soy protein isolate; carbohydrate: modified tapioca and
corn starch; fat: about 50% canola oil, about 20% corn oil, about
30% high-oleic sunflower oil, n6:n3 ratio about 5; fibre (inner pea
fibre, outer pea fibre, acacia gum and fructo-oligosaccharides);
water; vitamin A; vitamin C vitamin D; vitamin E; vitamin K;
vitamin B.sub.1; Vitamin B.sub.2; vitamin B.sub.6; niacin; folic
acid; pantothenic acid; vitamin B.sub.12; biotin; calcium;
magnesium; zinc; iron; copper; manganese; iodine; sodium;
potassium; chloride; chromium; molybdenum; fluoride and
selenium.
[0036] The compositions have the following nutrient profiles (per
1500 ml):
TABLE-US-00002 Nutrient Composition Example C Example D Caloric
Density 0.5 kcal/ml 0.75 kcal/ml Protein (g) 84 100 Carbohydrate
(g) 47 124 Fat (g) 25 37.5 Dietary Fibre (g) 22.5 22.5 Vitamin A
(.mu.g RE) 1950 1950 Vitamin D (.mu.g) 22.5 22.5 Vitamin E (mg
.alpha. TE) 30 30 Vitamin K (.mu.g) 124.5 124.5 Vitamin C (mg) 225
225 Vitamin B1 (mg) 2.7 2.7 Vitamin B2 (mg) 3.0 3.0 Niacin (mg) 27
27 Vitamin B6 (mg) 3.9 3.9 Folic Acid (.mu.g) 540 540 g Pantothenic
Acid (mg) 11.25 11.25 Vitamin B 12 (.mu.g) 6.75 6.75 Biotin (.mu.g)
67.5 67.5 Calcium (mg) 1350 1350 Magnesium (mg) 450 450 Zinc (mg)
22.5 22.5 Iron (mg) 24 24 Copper (mg) 2.25 2.25 Manganese (mg) 4.95
4.95 Iodine (.mu.g) 225 225 Sodium (mg) 1350 1350 Potassium (mg)
2550 2550 Chloride (mg) 2100 2100 Chromium (.mu.g) 112.5 112.5
Molybdenum (.mu.g) 225 225 Selenium (.mu.g) 112.5 112.5 Fluoride
(mg) 2.25 2.25
* * * * *