U.S. patent application number 10/228722 was filed with the patent office on 2003-02-27 for carbohydrate formulation (prebiotic adjuvant) for enhancement of immune response.
Invention is credited to Carrie, Anne-Lise, Haschke, Ferdinand, Kratky, Zdenek, Link-Amster, Harriet, Rochat, Florence.
Application Number | 20030040492 10/228722 |
Document ID | / |
Family ID | 8171132 |
Filed Date | 2003-02-27 |
United States Patent
Application |
20030040492 |
Kind Code |
A1 |
Haschke, Ferdinand ; et
al. |
February 27, 2003 |
Carbohydrate formulation (prebiotic adjuvant) for enhancement of
immune response
Abstract
A prebiotic for enhancement of an immune response, a nutritional
composition for enhancement of an immune response; use of a
prebiotic in the manufacture of a medicament or nutritional
composition for enhancement of an immune response; use of a
prebiotic in the manufacture of a medicament or nutritional
composition for the prevention or treatment of measles; a method of
enhancing an immune response which comprises administering an
effective amount of a prebiotic; and a method of prevention or
treatment of measles which comprises administering an effective
amount of a prebiotic. In preferred embodiments the prebiotic
comprises a fructo-oligosaccharide.
Inventors: |
Haschke, Ferdinand;
(Minchen, DE) ; Carrie, Anne-Lise; (Unteriberg,
CH) ; Kratky, Zdenek; (Maracon, CH) ;
Link-Amster, Harriet; (Vevey, CH) ; Rochat,
Florence; (Montreux, CH) |
Correspondence
Address: |
WINSTON & STRAWN
PATENT DEPARTMENT
1400 L STREET, N.W.
WASHINGTON
DC
20005-3502
US
|
Family ID: |
8171132 |
Appl. No.: |
10/228722 |
Filed: |
August 26, 2002 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
|
|
10228722 |
Aug 26, 2002 |
|
|
|
PCT/EP01/01627 |
Feb 14, 2001 |
|
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Current U.S.
Class: |
514/23 ;
424/93.45; 514/53; 514/54; 514/61 |
Current CPC
Class: |
A61P 33/00 20180101;
A61K 31/733 20130101; A61P 17/00 20180101; A61P 37/00 20180101;
A61P 37/04 20180101; A61P 31/04 20180101; A61P 31/12 20180101; A61P
31/00 20180101 |
Class at
Publication: |
514/23 ; 514/53;
514/54; 514/61; 424/93.45 |
International
Class: |
A61K 045/00; A61K
031/70; A61K 031/715; A61K 031/7012 |
Foreign Application Data
Date |
Code |
Application Number |
Mar 1, 2000 |
EP |
00200735.9 |
Claims
What is claimed is:
1. A composition comprising at least one prebiotic for enhancement
of an immune response.
2. The composition according to claim 1, wherein the prebiotic
comprises an oligosaccharide produced from glucose, galactose,
xylose, maltose, sucrose, lactose, starch, xylan, hemicellulose,
inulin, or a mixture thereof.
3. The composition according to claim 1, wherein the prebiotic
comprises a fructo-oligosaccharide.
4. The composition according to claim 1, wherein the prebiotic
comprises a mixture of fructo-oligosaccharide and inulin.
5. The composition according to claim 1, wherein the prebiotic
comprises, by weight, about 60% to about 80% fructo-oligosaccharide
and about 20% to about 40% inulin.
6. The composition according to claim 1, which further comprises a
probiotic.
7. The composition according to claim 6, wherein the probiotic is
selected from the group consisting of Bifidobacterium bifidum and
Streptococcus thermophilus.
8. The composition according to claim 1 in combination with a
carrier.
9. The composition according to claim 8, wherein the carrier is a
cereal, a fermented milk, a yogurt, a cheese, a renneted milk, a
confectionery bar, a beverage, milk powder, a soy-based product, a
non-milk fermented product, or a supplement for clinical
nutrition.
10. A method of manufacturing a medicament or nutritional
composition for enhancement of an immune response, which comprises
including in the composition a prebiotic in an amount sufficient to
elicit an enhancement of an immune response when administered to a
subject.
11. The method according to claim 10, wherein the medicament or
nutritional composition is prepared for administration for the
prevention or treatment of measles.
12. The method according to claim 10, wherein the prebiotic
comprises an oligosachharide produced from glucose, galactose,
xylose, maltose, sucrose, lactose, starch, xylan, hemicellulose,
inulin, or a mixture thereof.
13. The method according to claim 10, wherein the prebiotic
comprises a fructo-oligosaccharide.
14. The method according to claim 10, wherein the prebiotic
comprises a mixture of fructo-oligosaccharide and inulin.
15. The method according to claim 10, wherein the prebiotic
comprises, by weight, about 60% to about 80% fructo-oligosaccharide
and about 20% to about 40% inulin.
16. The method according to claim 10, wherein the medicament or
nutritional composition further comprises a probiotic.
17. The method according to claim 16, wherein the probiotic is
selected from the group which consists of Bifidobacterium bifidum
and Streptococcus thermophilus.
18. A method of enhancing an immune response which comprises
administering at least one prebiotic or composition comprising at
least one prebiotic wherein the prebiotic is present in an amount
to elicit enhancement of an immune response.
19. The method according to claim 18, wherein the at least one
prebiotic or composition comprising at least one prebiotic is
administered to a subject for prevention or treatment of
measles.
20. The method according to claim 18, wherein the prebiotic
comprises an oligosaccharide produced glucose, galactose, xylose,
maltose, sucrose, lactose, starch, xylan, hemicellulose, inulin, or
a mixture thereof.
21. The method according to claim 18, wherein the prebiotic
comprises a fructo-oligosaccharide.
22. The method according to claim 18, wherein the prebiotic
comprises a mixture of fructo-oligosaccharide and inulin.
23. The method according to claim 18, wherein the prebiotic
comprises, by weight, about 60% to about 80% fructo-oligosaccharide
and about 20% to about 40% inulin.
24. The method according to claim 18, wherein the medicament or
nutritional composition further comprises a probiotic.
25. The method according to claim 24, wherein the probiotic is
selected from the group which consists of Bifidobacterium bifidum
and Streptococcus thermophilus.
Description
CROSS-REFERENCE TO RELATED APPLICATIONS
[0001] This application is a continuation of the US national stage
designation of International application PCT/EP01/01627 filed Feb.
14, 2001, the entire content of which is expressly incorporated
herein by reference thereto.
BACKGROUND ART
[0002] The present invention relates to a carbohydrate formulation
for enhancement of an immune response, a nutritional composition
for enhancement of an immune response; and to the use of a
prebiotic formulation in the manufacture of a medicament or
nutritional composition for enhancement or improvement of an immune
response to a vaccination, in particular measles vaccination, and
prevention and supportive treatment of diseases and infections e.g.
bacterial, viral and parasitic. The invention also relates to a
method of enhancing an immune response which comprises
administering an effective amount of a prebiotic mixture; and a
method of prevention or supportive treatment of diseases which
comprises administering an effective amount of a prebiotic
formulation.
[0003] It is well known that prebiotics comprise carbohydrates and
more specifically, oligosaccharides. Furthermore it is known that
they have widely been used as functional food ingredients. They
resist hydrolysis by enzymes of the human digestive tract, can
reach the colon undegraded and provide a carbohydrate substance
particularly suited to the growth of bifidobacteria.
Oligosachharides may be produced from glucose, galactose, xylose,
maltose, sucrose, lactose, starch, xylan, hemicellulose, inulin, or
a mixture thereof. Purified commercially available products such as
fructo-oligosaccharides contain greater than about 95% solids in
the form of oligosaccharides.
[0004] Measles is a major public health problem, infecting
approximately 70 million children annually, and it is estimated
that 2 million die each year from the disease itself or its
complications. In addition to fever and rash, the consequences of
measles include acute diarrhea or dysentery, pneumonia,
encephalitis, and blindness due to acute vitamin A deficiency. Thus
in developing countries, case fatality rates may reach 10-20%
(Semba R. D. Clin. Infect. Dis. 1994; 19:489-499).
[0005] Measles prevention is possible by maintaining a high level
of immunization through vaccination with attenuated live vaccine.
Measles vaccine is usually given at 15 months but may be given
earlier (at 6-9 months of age) in areas where disease is frequently
occurring and poses a threat to health and life of children.
However, the response to measles vaccination at less than 12 months
of age is suboptimal because infants may transplacentally acquire
maternal antibodies that disappear at a variable rate. Because the
seroconversion rate following immunization is not 100% and there
may be some waning of immunity with time, a second immunization
against measles is usually indicated.
[0006] An elevated response to early measles vaccination may
therefore offer substantial and longer lasting protection until a
second vaccine is administered, and the present invention provides
a solution that addresses the problems set out above.
SUMMARY OF THE INVENTION
[0007] Remarkably, it has now been found that children fed a diet
comprising a prebiotic formulation have a significantly enhanced
immune response after vaccination than children fed a control diet
without this prebiotic formulation.
[0008] Consequently, in a first aspect, the present invention
provides a composition comprising at least one prebiotic for
enhancement of an immune response.
[0009] In a second aspect, the invention provides use of a
prebiotic in the manufacture of a medicament or nutritional
composition for enhancement of an immune response.
[0010] In a third aspect, the invention provides use of a prebiotic
or composition in the manufacture of a medicament or nutritional
composition for the prevention or supportive treatment of
measles.
[0011] In a forth aspect, the invention provides a method of
enhancing an immune response which comprises administering an
effective amount of a prebiotic or composition comprising at least
one prebiotic.
[0012] In a fifth aspect, the invention provides a method of
prevention or supportive treatment of diseases such as measles
which comprises administering an effective amount of a prebiotic or
composition comprising at least one prebiotic.
[0013] Advantageously, an embodiment of the composition is a
nutritional composition which comprises at least one prebiotic.
Preferably, the prebiotic comprises an oligosachharide produced
from glucose, galactose, xylose, maltose, sucrose, lactose, starch,
xylan, hemicellulose, inulin, or a mixture thereof. More
preferably, the oligosaccharide comprises fructo-oligosaccharide.
Most preferably, the prebiotic is a mixture of
fructo-oligosaccharide and inulin, comprising PREBIO1.RTM. or a
mixture of commercially available RAFTILOSE.RTM. and
RAFTILINE.RTM..
[0014] The prebiotic advantageously comprises about 50% to about
90% fructo-oligosaccharide. More preferably, it comprises about 60%
to about 80% fructo-oligosaccharide. Most preferably, it comprises
about 70% fructo-oligosaccharide.
[0015] Preferably, the prebiotic comprises about 10% to about 50%
inulin. More preferably, it comprises about 20% to about 40%
inulin. Most preferably, it comprises about 30% inulin.
[0016] The composition may include a prebiotic in addition to the
prebiotic. Preferably, the probiotic is selected from the group
consisting of Bifidobacterium bifidum and streptococcus
thermophilus. Preferably the Bifidobacterium bifidum is
Bifidobacterium lactis.
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS
[0017] An advantage of the present invention is that it provides an
elevated immune response after vaccination and therefore offers
substantial protection until a second follow-up vaccine can be
administered.
[0018] Another advantage of the present invention is that it
provides an elevated response to early measles vaccination may
therefore offer substantial protection against measles until a
second measles vaccine is administered.
[0019] Yet another advantage of the present invention is that it
may be employed to enhance an immune response, e.g., protection
against measles, by simple consumption of food before, during, and
after the vaccination period. It will be appreciated that
intravenous or subcutaneous administration of a drug requires
expertise, and compared to oral administration it is not as safe,
convenient or acceptable to the patient. In the light of these
concerns, the invention provides the clear advantage of a
nutritional and/or therapeutic product which may be administered
orally although other forms of administration can be used.
[0020] Additional features and advantages of the present invention
are described in, and will be apparent from, the following
description of the presently preferred embodiments.
[0021] In an embodiment, a nutritional composition comprises a milk
based cereal together with a prebiotic formulation. Preferably the
milk based cereal is an infant cereal which acts as a carrier for
the prebiotic formulation.
[0022] The most preferred prebiotic comprises a mixture of
fructo-oligosaccharides and inulin in the amounts by weight of 70%
fructo-oligosaccharides and 30% inulin.
[0023] If desired and advantageously, the composition may include a
source of protein and/or a source of carbohydrate and/or a source
of fat.
[0024] Dietary protein is preferred as a source of protein. The
dietary protein may be any suitable dietary protein; for example
animal protein, such as milk protein, meat protein or egg protein;
vegetable protein, such as soy protein, wheat protein, rice
protein, and pea protein; a mixture of free amino acids; or a
combination thereof. Milk proteins such as casein, whey proteins or
soy protein or a mixture thereof are particularly preferred.
[0025] The composition may comprise a fat source, and if so the fat
source preferably provides about 5% to about 55% of the energy of
the composition; for example about 20% to about 50% of the energy.
Lipid making up the fat source may be any suitable fat or fat
mixture. For example soy oil, palm oil, coconut oil, safflower oil,
sunflower oil, corn oil, canola oil, lecithins or animal fat such
as milk fat may be added if desired.
[0026] A source of carbohydrate may also be included. If so, it
preferably provides about 40% to about 80% of the energy of the
composition. Any suitable carbohydrate may be used, for example
sucrose, lactose, glucose, fructose, corn syrup solids,
maltodextrin, or a mixture thereof.
[0027] Also, dietary fibers can be included, if desired. When
present, it comprises up to about 5% of the weight of the
nutritional composition. The dietary fibers may be provided from
any suitable origin, including for example soy, pea, oat, pectin,
guar gum, gum arabic, fructo-oligosaccharide or a mixture
thereof.
[0028] Suitable vitamins and minerals may be included in the
nutritional composition in an amount to meet the appropriate or
desirable guidelines.
[0029] One or more food grade emulsifiers may be included in the
nutritional composition if desired; for example diacetyl tartaric
acid esters of mono- and di-glycerides, lecithin and mono- or
di-glycerides or a mixture thereof. Similarly suitable salts and/or
stabilizers may be included.
[0030] The nutritional composition for enhancing an immune response
e.g., following measles, vaccination is preferably enterally
administrable; for example in the form of a powder, tablet,
capsule, a liquid concentrate, solid product or a ready-to-drink
beverage. If it is desired to produce a powdered nutritional
formula, the homogenized mixture is transferred to a suitable
drying apparatus such as a spray drier or freeze drier and
converted to powder.
[0031] Alternatively, a usual food product may be enriched with the
an embodiment of composition. For example, a fermented milk, a
yogurt, a fresh cheese, a renneted milk, a confectionery bar,
breakfast cereal flakes or bars, a drink, milk powder, soy-based
product, non-milk fermented product or a nutritional supplement for
clinical nutrition. Then, the amount of the composition added is
preferably at least about 0.01% by weight.
[0032] An embodiment of the composition may be included in article
of confectionery, for example a sweet or sweetened beverage.
EXAMPLES
[0033] The following examples are given by way of illustration only
and in no way should be construed as limiting the subject matter of
the present application. Percentages and parts are by weight unless
otherwise indicated.
Example 1
Nutritional Composition
[0034] A composition was made by blending a cereal product with 4%
prebiotic (70% fructo-oligosaccharide, 30% inulin). Its composition
is indicated below:
1 component amount in % Cereal product 96% Prebiotic 4%
[0035] Infants received 1-2 servings of this composition or cereal
without the prebiotic (per serving 25g cereal and 70 ml of water)
per day throughout a 10 week study period. The amount of cereal
consumed per day was recorded. No restrictions were made for intake
of milk, solids or family food.
[0036] Remarkably, if a nutritional composition according to the
invention was consumed it was found that the concentration of IgG
antibody 10 weeks after a measles vaccination was significantly
higher compared to consumption of a similar nutritional composition
without the prebiotics. Remarkably the concentration of IgG
antibodies in the blood has been found to be significantly
increased when the composition comprising prebiotics was consumed.
Surprisingly the level of IgG was at least 50% higher.
[0037] A double-blind randomized controlled study was conducted to
examine the effects on the immune response after measles
vaccination of an infant cereal with milk (Nestle) supplemented
with a "prebiotic" mixture of fructo-oligosaccharides and inulin
(PREBIO1.RTM.).
[0038] Eight months-old infants with mixed feeding (breast-,
formula, and solids) were randomly assigned to two groups. Both
groups received the cereals during a period of 10 weeks, and one
group was supplemented with the PREBIO1.RTM. mixture of
fructo-oligosaccharides and inulin (Ig per 25g cereal). Four weeks
after introduction of the cereals, all infants were vaccinated with
live attenuated measles vaccine (Biofarma, Indonesia). Blood was
collected for IgG measles antibody measurement (Elisa; PanBio,
Australia) immediately before and 6 weeks after vaccination.
Growth, general health status and mild reactions after vaccination
(e.g. fever, runny nose) were recorded.
[0039] Out of 50 infants enrolled, 24 infants having their diets
supplemented with a composition according to the invention (S) and
25 controls not having their diets supplemented with a composition
according to the invention (C) completed the study.
Post-vaccination IgG antibody levels were significantly higher
(p<0.05) in group S.
[0040] IgG antibodies increased 6.6 and 4.2 fold in groups S and C
respectively (p<0.03). The post-vaccination IgG positivity rates
were 96% (S) and 88% (C). Mild reactions were significantly more
often observed in group S (p<0.01). No differences in growth and
overall health status were observed.
[0041] It was concluded that regular consumption of infant cereals
with the prebiotic composition according to the invention improved
immune response e.g., after measles vaccination.
Example 2
Food supplement
[0042] A food supplement was prepared by mixing or blending
fructo-oligosaccharide with inulin in the proportions by weight of
about 70% fructo-oligosaccharide to about 30% inulin. The resulting
prebiotic mixture may be added or blended with any suitable
carrier, for example a fermented milk, a yogurt, a fresh cheese, a
renneted milk, a confectionery bar, breakfast cereal flakes or
bars, a drink, milk powder, soy-based product, non-milk fermented
product or a nutritional supplement for clinical nutrition.
[0043] It should be understood that various changes and
modifications to the presently preferred embodiments described
herein will be apparent to those skilled in the art. Such changes
and modifications can be made without departing from the spirit and
scope of the present invention and without diminishing its
attendant advantages. It is therefore intended that such changes
and modifications be covered by the appended claims.
* * * * *