U.S. patent application number 10/015782 was filed with the patent office on 2002-05-30 for insulin supplemented infant formula.
This patent application is currently assigned to INSOTECH LTD.. Invention is credited to Shehadeh, Naim.
Application Number | 20020064549 10/015782 |
Document ID | / |
Family ID | 27624774 |
Filed Date | 2002-05-30 |
United States Patent
Application |
20020064549 |
Kind Code |
A1 |
Shehadeh, Naim |
May 30, 2002 |
INSULIN SUPPLEMENTED INFANT FORMULA
Abstract
An infant formula in a powder or solution form including
nutritional components and an insulin supplement. A method of
feeding an infant including the steps of dissolving an infant
formula powder containing nutritional components and an insulin
supplement in water for obtaining a solution including said
nutritional components and said insulin supplement and feeding the
infant with the solution.
Inventors: |
Shehadeh, Naim; (Kfar Yasif,
IL) |
Correspondence
Address: |
DR. MARK FRIEDMAN LTD.
C/o Bill Polkinghorn
Discovery Dispatch
9003 Florin Way
Upper Marlboro
MD
20772
US
|
Assignee: |
INSOTECH LTD.
|
Family ID: |
27624774 |
Appl. No.: |
10/015782 |
Filed: |
December 17, 2001 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
|
|
10015782 |
Dec 17, 2001 |
|
|
|
09701652 |
Nov 30, 2000 |
|
|
|
Current U.S.
Class: |
424/439 ;
514/1.1; 514/5.5; 514/5.9 |
Current CPC
Class: |
A23V 2002/00 20130101;
A61K 38/28 20130101; A23V 2002/00 20130101; Y10S 514/866 20130101;
A23L 33/18 20160801; A61K 9/14 20130101; A61P 3/10 20180101; A23V
2250/156 20130101; A23V 2250/06 20130101; A23V 2250/30 20130101;
A23V 2250/1882 20130101; A23L 33/40 20160801; A23V 2250/70
20130101; A61K 9/0095 20130101 |
Class at
Publication: |
424/439 ;
514/3 |
International
Class: |
A61K 047/00; A61K
038/28 |
Foreign Application Data
Date |
Code |
Application Number |
Jun 3, 1999 |
US |
PCT/US99/12592 |
Claims
What is claimed is:
1. An infant formula in a powder or solution form comprising
nutritional components and an insulin supplement such that when the
infant formula is fed to an infant a chance of the infant of
developing diabetes is reduced; wherein said insulin is in a
concentration range of about 1,000 to 100,000 micro units/100 ml of
solution or 8,300-750,000 micro units/100 grams of powder.
2. The infant formula of claim 1, wherein said insulin has an amino
acid sequence of human insulin.
3. The infant formula of claim 1, wherein said insulin is
recombinant.
4. The infant formula of claim 3, wherein said insulin has an amino
acid sequence of human insulin.
5. The infant formula of claim 1, wherein said insulin is
synthetic.
6. The infant formula of claim 5, wherein said insulin has an amino
acid sequence of human insulin.
7. The infant formula of claim 1, wherein said insulin is purified
natural insulin.
8. The infant formula of claim 7, wherein said insulin has an amino
acid sequence of human insulin.
9. The infant formula of claim 1, wherein said insulin is
biologically active.
10. The infant formula of claim 1, wherein said insulin is in a
concentration range of about 2,000 to 55,000 micro units/100 ml of
solution or 17000-400,000 micro units/100 grams of powder.
11. The infant formula of claim 1, wherein at least some of said
nutritional components are derived from milk.
12. The infant formula of claim 1, wherein at least some of said
nutritional components are derived from soy.
13. A method of feeding an infant comprising the steps of
dissolving an infant formula powder containing nutritional
components and an insulin supplement in water for obtaining a
solution including said nutritional components and said insulin
supplement and feeding the infant with said solution, thereby
reducing a chance of the infant of developing diabetes; wherein
said insulin is in a concentration range of about 1,000 to 100,000
micro units/100 ml of solution or 8,300-75,0000 micro units/100
grams of powder.
14. The method of claim 13, wherein said insulin has an amino acid
sequence of human insulin.
15. The method of claim 13, wherein said insulin is
recombinant.
16. The method of claim 15, wherein said insulin has an amino acid
sequence of human insulin.
17. The method of claim 13, wherein said insulin is synthetic.
18. The method of claim 17, wherein said insulin has an amino acid
sequence of human insulin.
19. The method of claim 13, wherein said insulin is purified
natural insulin.
20. The method of claim 19, wherein said insulin has an amino acid
sequence of human insulin.
21. The method of claim 13, wherein said insulin is biologically
active.
22. The method of claim 13, wherein said insulin is in a
concentration range of about 17,000 to 400,000 .mu.U per 100 grams
of said powder or 2,000-55,000 .mu.U per 100 milliliters of said
solution.
23. The method of claim 13, wherein at least some of said
nutritional components are derived from milk.
24. The method of claim 13, wherein at least some of said
nutritional components are derived from soy.
Description
[0001] This application is a continuation in part of U.S. patent
application Ser. No. 09/701,652 filed in Nov. 30, 2000.
FIELD AND BACKGROUND OF THE INVENTION
[0002] The present invention relates to an infant formula and, more
particularly, to an insulin supplemented infant formula.
[0003] Breastfeeding, the natural feeding mode, has multiple
beneficial effects on the infant. First, it is known to be the most
suitable diet for infant's nutritional requirements. Second, it
provides the infant with immune protection against a wide range of
infection related diseases (1). Third, as it contains active
insulin molecules it protects the infant against the development of
Type-1 diabetes (2-3). Fourth, insulin present in milk enhances
small intestinal growth and development (4).
[0004] Type-1 diabetes, which is insulin dependent diabetes
mellitus (IDDM), is the consequence of progressive autoimmune
pancreatic .beta. cell destruction during an initially asymptomatic
period that may extend many years (5-6). The etiology is
multifactorial, with genetic and environmental factors contributing
to the autoimmune destruction of the .beta. cells. The fact that
concordance for IDDM in monozygotic twins is not more than 30-50%
(7) and that 90% of patients with newly diagnosed IDDM do not have
an affected first-degree relative having IDDM (8), as well as the
sudden increase in incidence of IDDM witnessed over the last ten
years (9), have been taken as indication of the importance of
environmental factors in triggering the development of the
autoimmune process in genetically susceptible individuals.
[0005] Many studies show that type I diabetes is related to cow's
milk consumption and neonatal feeding practices (2,10). In the
case-control studies (including a study conducted in the Juvenile
Diabetes Unit of the Rambam Medical Center, Haifa, Israel),
patients with type I diabetes were more likely to have been
breast-fed for less than 3 months and to have been exposed to cow's
milk proteins before 3 months of age (3). Moreover, the immune
system of patients with IDDM recognizes cow's milk proteins, as
demonstrated by antibodies assays and lymphocytes activity tests
(11). These data emphasize the importance of diet and orally
administered proteins on the development of autoimmune
diabetes.
[0006] In animal models, It has been shown that oral feeding of a
specific antigen can suppress the immune system and cause an
antigen-specific reduction in many types of immune responses,
including T cell proliferation; delayed type hypersensitivity, and
antibody production (12-15). Oral administration of insulin
generates active cellular mechanisms that suppress the development
of autoimmune diabetes (16). These results have paved the way to
the "oral tolerance approach" and oral insulin treatment is already
taking place in human trials planned to prevent type 1 diabetes in
high risk groups (17).
[0007] As shown below, prior art infant formulas, although
attempting to mimic as much as possible breast milk, are very low
in immunologically recognizable insulin as compared with human
milk. The level of active insulin in these formulas is probably
zero, due to the harsh conditions associated with their
manufacture.
[0008] There is thus a widely recognized need for, and it would be
highly advantageous to have, an infant formula supplemented with
insulin.
SUMMARY OF THE INVENTION
[0009] According to one aspect of the present invention there is
provided an infant formula in a powder or solution form comprising
nutritional components and an insulin supplement such that when the
infant formula is fed to an infant a chance of the infant of
developing diabetes is reduced; wherein said insulin is in a
concentration range of about 1,000 to 100,000 micro units/100 ml of
solution or 8,300-750,000 micro units/100 grams of powder.
[0010] According to another aspect of the present invention there
is provided a method of feeding an infant comprising the steps of
dissolving an infant formula powder containing nutritional
components and an insulin supplement in water for obtaining a
solution including the nutritional components and the insulin
supplement and feeding the infant with the solution thereby
reducing a chance of the infant of developing diabetes; wherein
said insulin is in a concentration range of about 1,000 to 100,000
micro units/100 ml of solution or 8,300-75,0000 micro units/100
grams of powder.
[0011] According to further features in preferred embodiments of
the invention described below, the insulin is recombinant
insulin.
[0012] According to still further features in the described
preferred embodiments the insulin is synthetic.
[0013] According to still further features in the described
preferred embodiments the insulin is purified natural insulin.
[0014] According to still further features in the described
preferred embodiments the insulin is biologically active.
[0015] According to still further features in the described
preferred embodiments the insulin is in a concentration range of
about 17,000 to 400,000 .mu.U per 100 grams of said powder or
2,000-55,000 .mu.U per 100 milliliters of said solution.
[0016] According to still further features in the described
preferred embodiments the insulin has an amino acid sequence of
human insulin.
[0017] According to still further features in the described
preferred embodiments at least some of the nutritional components
are derived from milk or soy.
[0018] The present invention successfully addresses the
shortcomings of the presently known configurations by providing an
infant formula which is more similar to human milk, protects from
the development of Type-1 diabetes and improve the development and
maturation of infants intestine.
DESCRIPTION OF THE PREFERRED EMBODIMENTS
[0019] The present invention is of an infant formula supplemented
with insulin, preferably human insulin, which can be used to feed
infants. Specifically, the present invention can be used to protect
infants of syndromes associated with feed devoid of insulin fed to
them in the first year of their lives. The present invention
renders infant formulas more similar to human milk.
[0020] The principles and operation of an infant formula according
to the present invention may be better understood with reference to
the drawings and accompanying descriptions.
[0021] Before explaining at least one embodiment of the invention
in detail, it is to be understood that the invention is not limited
in its application to the details of construction and the
arrangement of the components set forth in the following
description or illustrated in the drawings. The invention is
capable of other embodiments or of being practiced or carried out
in various ways. Also, it is to be understood that the phraseology
and terminology employed herein is for the purpose of description
and should not be regarded as limiting.
[0022] Epidemiological and experimental animal data suggest that
insulin content in infant diet may play an important role in
preventing autoimmune diabetes and improving intestinal
development.
[0023] It is shown in the Examples section hereinunder that the
level of immunologically recognized insulin in a variety of
commonly used infant formulas is very low, at least four to ten
times lower as compared with human milk, probably even lower.
Although not tested, the level of active insulin in such formulas
is expected to be zero due to the harsh conditions associated with
their manufacture. Soy-based infant formulas, are devoid of milk
content, and are therefore completely devoid of both
immunologically recognizable insulin, not to mention active
insulin.
[0024] Moreover, it has been shown that exposure to bovine insulin
present in fresh cow milk, which differs from human insulin only by
three amino acids, may break the tolerance to insulin and lead to
autoimmune diabetes (18).
[0025] To overcome these two obstacles in infant feeding: the lack
of insulin in infant formulas and the risk to break immune
tolerance to insulin when using fresh cow milk, it is herein
suggest for the first time to add human insulin to infant
formula.
[0026] Addition of insulin to infant formula leads for the
following beneficial effects. First, it renders the infant formula
more similar to human milk. Second, it protects from the
development of Type-1 diabetes. Third, it improve the development
and maturation of infants intestine. The addition of insulin to
infant formula is safe for at least two reasons. First, the
concentration of insulin is selected similar to that found in human
milk. Second, oral insulin administration is already used in
several human trials (17).
[0027] Thus, in accordance with one aspect of the present invention
there is provided an infant formula in a powder or solution form
which formula includes nutritional components and an insulin
supplement.
[0028] In accordance with another aspect of the present invention
there is provided a method of feeding an infant. The method is
effected by executing the following steps. First an infant formula
powder containing nutritional components and an insulin supplement
is solubilized in water for obtaining a solution including the
nutritional components and the insulin supplement. Second, the
solution is fed to the infant.
[0029] As exemplified in the Examples section below, the
nutritional components may include milk or soy derived nutritional
components. They may additionally include one or more of the
following ingredients: lactose, vegetable oils, skimmed milk
powder, whey protein concentrate, Sodium, Calcium, Phosphorus,
Potassium, Chloride, Iron, Magnesium, Taurine, Vitamins, Glucose
syrup, soy protein isolate, Sucrose, Maltodextrine, Methionine,
Taurine, Carnitine, and trace elements.
[0030] According to a preferred embodiment of the present
invention, the insulin is selected from the following insulin
types: recombinant insulin, synthetic insulin, purified natural
insulin, biologically active insulin and insulin having an amino
acid sequence of human insulin (e.g., human insulin). Some of these
types are overlapping and therefore the insulin of choice may be
categorized to more than a single type of the types listed. Human
recombinant insulin is available in a pure form from Eli Lilly
& Co, USA. Human natural purified insulin is available in a
pure form from Novo Nordisk, Denmark. Crude extracts may also be
useful, depending on the method of their manufacturing. Synthetic
insulin may be manufactured using commercially available building
units for Boc and Fmoc chemistry peptide synthesis, as well known
in the art.
[0031] According to another preferred embodiment of the present
invention the concentration of the insulin in the solution is
similar to the concentration in human milk. Thus, according to a
preferred embodiment the insulin concentration is in the range of
about 25000-75000 .mu.U per 100 grams of the powder (which is
diluted about 7.5 fold to form the solution) or 3000-10000 .mu.U
per 100 milliliters of the solution, preferably 3000-6000,
optimally about 4200 .mu.U per 100 milliliters of the solution.
EXAMPLES
[0032] Reference is now made to the following examples, which
together with the above descriptions, illustrate the invention in a
non limiting fashion.
Materials and Methods
[0033] Milk Samples and insulin measurements:
[0034] Human breast milk samples were collected from mothers
between the second and the 30th day after delivery of full term
pregnancies. Cow milk samples were taken from pooled fresh
commercially available milk. Cow milk formulas were prepared
according to manufacturer instructions. All samples were stored in
polypropylene tubes at -20.degree. C. Fat-free infranatant were
obtained by diluting the milk samples with PBS (10 mM
KH.sub.2PO.sub.4, 0.15 M NaCl, pH 7.4) and centrifuged at 100,000 g
for 60 min. Clear infranatant were aspirated and stored at
-20.degree. C. Insulin concentrations were determined by
radioimmunoassay with commercial kit (Bio Data, Sorin) using human
insulin as standard.
Experimental Results
[0035] As shown in Table 1 below, insulin concentration is
significantly higher in human milk (about 42 .mu.U/ml) compared
with commercial fresh cow milk (about 17 .mu.U/ml) and infant
formulas (about 4-12 .mu.U/ml). Insulin levels in infant formulas
is very low and is similar to the levels recorded for negative
control solution (0.5% bovine serum albumin solution, about 6
.mu.U/ml).
1TABLE 1 Insulin concentration in milk samples Insulin
Concentration Milk Sample (mean in .mu.U/ml) Human milk, n = 29 42
Fresh pooled cow milk, n = 4 17.08 (Tnuvah, Israel) Materna
Premium, n = 2 7.5 (Trima, Israel) Remedia Formula, n = 3 7.0
(Humna Milchwerke ,Germany) Similac, n = 2 11.85 (Ross-Abbott,
Irland) Enfalac Premature, n = 1 5.2 (Mead Johnson, USA)
Pregestimil, n = 2 3.8 (Mead Johnson, USA) 0.5% Bovine Serum
Albumin 6.5 solution, n = 2 (Sigma, USA)
[0036] Tables 2 and 3 below provide exemplary compositions of dry
and in solution milk- and soy-bases infant formulas according to
the present invention.
Infant Formula I (Milk-Based)
[0037] The formula comprises the following ingredients: lactose,
vegetable oils, skimmed milk powder, whey protein concentrate,
Sodium, Calcium, Phosphorus, Potassium, Chloride, Iron, Magnesium,
Taurine, Vitamins and Insulin.
2 TABLE 2 Powder Solution Unit 100 g 100 ml General Comp. Protein
gram 11.1 1.5 Fat gram 25.9 3.5 Lactose gram 55.5 7.5 Water gram
2.5 -- Ash gram 2.06 0.27 Insulin .mu.U 22500-75000 3000-10000
Vitamins Vitamin A I.U. 1500 200 Vitamin D I.U. 300 40 Vitamin B mg
6 0.81 Vitamin K .mu.g 15 2.01 Vitamin B1 .mu.g 350 47.03 Vitamin
B2 .mu.g 450 60 Vitamin B6 .mu.g 222 30 Vitamin B12 .mu.g 0.66 0.09
Niacin mg 2 0.27 Folic Acid .mu.g 45 6 Calcium mg 4.44 0.06
Pantothenate Biotin .mu.g 11 1.5 Vitamin C mg 45 6.08 Minerals
Calcium mg 326 44 Phosphorus mg 219 29.6 Magnesium mg 37 5 Iron mg
7.4 1 Sodium mg 120.7 16.3 Potassium mg 373 50 Cal ratio -- 1.49
1.49 Amino Acid Profile Alanine mg 522 69.6 Arginine mg 368 49.1
Asparatic Acid mg 11.10 1.5 Cystine mg 191 25.5 Glutamic Acid mg
1423 189.7 Glycine mg 244 32.5 Histidine mg 262 34.9 Isoleucine mg
761 101.5 Leucine mg 12.20 1.62 Lysine mg 10.00 1.3 Methionine mg
270 36 Phenylalanine mg 461 62.3 Proline mg 962 128.3 Serine mg 681
90.8 Taurine mg 37 4.9 Threonine mg 686 91.5 Tryptophan mg 180 24
Tyrosine mg 463 61.7 Valine mg 775 103.3 Fatty Acid Profile
Caprylic (C8) % from fa 2.6 2.6 Capric (C10) % 2.1 2.1 Lauric (C12)
% 17.5 17.5 Meristic (C14) % 6.7 6.7 Palmitic (C16) % 11.2 11.2
Stearic (C18) % 11.8 11.8 Oleic (C18:1) % 37.0 37.0 Linoleic
(C18:2) % 10.0 10.0 Linolenic (C18:3) % 1.2 1.2 Supplement Insulin
.mu.U 22500-75000 3000-10000
Infant Formula II (Soy-Based)
[0038] The formula comprises the following ingredients: Glucose
syrup, vegetable oils, soy protein isolate, Sucrose, Maltodextrine,
Sodium, Calcium, Phosphorus, Potassium, chloride, Iron, Magnesium,
Vitamins, Methionine, Taurine, Camitine, trace elements and
Insulin.
3 TABLE 3 Powder Solution Unit 100 g 100 ml General Comp. Protein
gram 15 1.98 Fat gram 27.54 3.64 Carbohydrate gram 51.5 6.8
Linoleic Acid gram 4.5 0.6 Insulin .mu.U 22500-75000 3000-10000
Vitamins Vitamin A I.U. 1500 198 Vitamin D I.U. 300 39.7 Vitamin E
I.U. 10 1.32 Vitamin C mg 65 8.6 Vitamin K .mu.g 77 10.2 Vitamin B1
.mu.g 345 45.6 Vitamin B2 .mu.g 445 58.9 Vitamin B6 .mu.g 327 43.3
Vitamin B12 .mu.g 1.5 0.2 Niacin mg 7 0.93 Folic Acid .mu.g 76 10
Pantothenic Acid .mu.g 4.5 0.6 Biotin .mu.g 25 3.3 Choline mg 58
7.7 Minerals Calcium mg 500 66.2 Phosphoms mg 300 39.7 Magnesium mg
45 6 Iron mg 9.2 1.2 Zinc mg 4 0.53 Manganese pg 150 19.8 Copper
.mu.g 400 53 Iodine .mu.g 77 10.2 Sodium mg 200 26.5 Potassium mg
546 72.2 Chloride mg 400 53 Inositol mg 25 3.3 Carnitine mg 10 1.3
Ca/P ratio 1.67 1.67 Amino Acid Profile Alanine mg 640 85.3
Arginine mg 497 6.5 Aspartic Acid mg 1385 184.7 Cystine mg 242 32.3
Glutamic Acid mg 3065 408.7 Glycine mg 300 40 Histidine mg 382 50.9
Isoleucine mg 893 119.1 Leucine mg 1600 213.3 Lysine mg 1360 181.3
Methionine mg 406 54.1 Phenylalanine mg 650 86.7 Proline mg 1113
148.4 Serine mg 737 98.3 Taurine mg 51 6.8 Threonine mg 460 61.3
Tyrosine mg 621 82.8 Valine mg 947 126.3 Fatty Acid Profile
Caprylic (C8) % from fa 2.6 2.6 Capric (C10) % 2.1 2.1 Lauric (C12)
% 17.5 17.5 Meristic (C14) % 6.7 6.7 Palmitic (C16) % 11.2 11.2
Stearic (C18) % 11.8 11.8 Oleic (C18:1) % 37.0 37.0 Linoleic
(C18:2) % 10.0 10.0 Linolenic (C18:3) % 1.2 1.2 Supplement Insulin
.mu.U 22500-75000 3000-40000
[0039] Although the invention has been described in conjunction
with specific embodiments thereof, it is evident that many
alternatives, modifications and variations will be apparent to
those skilled in the art. Accordingly, it is intended to embrace
all such alternatives, modifications and variations that fall
within the spirit and broad scope of the appended claims.
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