U.S. patent application number 13/320021 was filed with the patent office on 2012-06-14 for immune stimulating composition comprising an extract of aronia sp. in combination with selenium and/or zinc.
This patent application is currently assigned to URSAPHARM ARZNEIMITTEL GMBH. Invention is credited to Josef Beuth, Klaus Eschmann.
Application Number | 20120148683 13/320021 |
Document ID | / |
Family ID | 41228588 |
Filed Date | 2012-06-14 |
United States Patent
Application |
20120148683 |
Kind Code |
A1 |
Eschmann; Klaus ; et
al. |
June 14, 2012 |
IMMUNE STIMULATING COMPOSITION COMPRISING AN EXTRACT OF ARONIA SP.
IN COMBINATION WITH SELENIUM AND/OR ZINC
Abstract
It pertains to a composition which comprises a combination of
Aronia extract in an amount of at least about 10 .mu.g/mg and
seleniumin in an amount from about 0.0001 .mu.g/mg to about 2.0
.mu.g/mg. The composition may further comprise zinc as additional
micronutrient. The composition may be formulated as a
pharmaceutical or a nutraceutical composition.
Inventors: |
Eschmann; Klaus;
(Kleinblittersdorf, DE) ; Beuth; Josef; (Koln,
DE) |
Assignee: |
URSAPHARM ARZNEIMITTEL GMBH
Saarbrucken
DE
|
Family ID: |
41228588 |
Appl. No.: |
13/320021 |
Filed: |
May 6, 2010 |
PCT Filed: |
May 6, 2010 |
PCT NO: |
PCT/EP2010/056190 |
371 Date: |
March 6, 2012 |
Current U.S.
Class: |
424/643 ;
424/702 |
Current CPC
Class: |
A61P 19/10 20180101;
Y02A 50/30 20180101; A61P 11/06 20180101; A61P 37/02 20180101; A61P
9/00 20180101; A61P 37/08 20180101; A61P 37/06 20180101; A61K 45/06
20130101; A61P 25/00 20180101; A61P 11/00 20180101; A61P 11/02
20180101; A61P 1/16 20180101; A61P 27/02 20180101; Y02A 50/411
20180101; A61P 9/10 20180101; A61P 17/00 20180101; A61P 17/04
20180101; A61P 37/00 20180101; A61P 19/00 20180101; A61K 33/04
20130101; A61P 19/02 20180101; A61P 1/04 20180101; A61P 31/18
20180101; A61P 31/04 20180101; A61P 21/00 20180101; A61P 1/00
20180101; A61P 1/02 20180101; A61K 36/73 20130101; A61P 29/00
20180101; A61P 27/06 20180101; A61P 31/12 20180101; A61P 3/10
20180101; A61P 17/06 20180101; A61P 31/10 20180101; A61P 33/00
20180101; A61K 33/30 20130101; A61P 13/12 20180101; A61P 35/00
20180101; A61K 33/04 20130101; A61K 2300/00 20130101; A61K 33/30
20130101; A61K 2300/00 20130101; A61K 36/73 20130101; A61K 2300/00
20130101 |
Class at
Publication: |
424/643 ;
424/702 |
International
Class: |
A61K 33/04 20060101
A61K033/04; A61P 29/00 20060101 A61P029/00; A61P 31/04 20060101
A61P031/04; A61P 31/10 20060101 A61P031/10; A61P 31/12 20060101
A61P031/12; A61P 19/02 20060101 A61P019/02; A61P 37/00 20060101
A61P037/00; A61P 1/00 20060101 A61P001/00; A61P 27/02 20060101
A61P027/02; A61P 25/00 20060101 A61P025/00; A61P 17/00 20060101
A61P017/00; A61P 37/06 20060101 A61P037/06; A61K 33/30 20060101
A61K033/30; A61P 33/00 20060101 A61P033/00 |
Foreign Application Data
Date |
Code |
Application Number |
May 12, 2009 |
EP |
09006414.8 |
Claims
1. A composition comprising Aronia extract in an amount of at least
about 10 .mu.g/mg and selenium in an amount of from about 0.0001
.mu.g/mg to about 2.0 .mu.g/mg.
2. The composition according to claim 1, further comprising
additional zinc.
3. The composition according to claim 2, comprising zinc in a
concentration from about 0.0001 mg/mg to about 0.5 mg/mg.
4. The composition according to any one of the preceding claim 1,
wherein the composition further comprises at least one
pharmaceutically or nutraceutically acceptable excipient or a
mixture thereof.
5. The composition according to claim 4, wherein the composition is
formulated as a pharmaceutical composition.
6. The composition according to claim 5 formulated for
peroral/oral, buccal, sublingual, mucosal or topical
administration.
7. The composition according to claim 4, wherein the composition is
formulated as a nutraceutical or supplementary neutraceutical
composition.
8. The composition according to claim 7, designed as an ingestible
solution or suspension, comprising an active ingredient in
dissolved or suspended form, or as a solid administration form, or
added as a food supplement to daily food products.
9. (canceled)
10. (canceled)
11. (canceled)
12. (canceled)
13. The composition according to claim 8, wherein the solid
administration form is in the form of tablets, capsules, or
dragees
14. A method of preparing a medicament comprising: mixing the
composition of claim 1 with one or more suitable pharmaceutically
excipient(s).
15. A method of treating inflammatory diseases or conditions,
bacterial infections, fungal infections, viral infections,
parasitic infections and combinations thereof, the method
comprising: administering an effective amount of the composition of
claim 1 to a subject in need thereof.
16. The method according to claim 15, wherein the inflammatory
disease or condition is associated with one or more selected from
the group consisting of autoimmune diseases, inflammatory bowel
disease, inflammatory diseases of eye, multiple sclerosis,
scleroderma, and graft-versus-host disease.
17. The method according to claim 15, wherein the inflammatory
disease is selected form the group consisting of Crohn's disease,
colitis, osteo- and rheumatoid arthritis, ankylosing spondylitis,
psoriatic arthritis, adult Still's disease, uveitis, Wegener's
granulomatosis, Behcet disease, Sjoegren's syndrome, sarcoidosis,
and conjunctivitis.
Description
[0001] The present invention relates to an immune stimulating
agent, and relates in particular to a composition comprising Aronia
extract and selenium for stimulating the immune system, and
pharmaceutical or nutraceutical compositions comprising the
same.
THE PRIOR ART
[0002] Aronia (chokeberry) is a deciduous shrub which belongs to
the plant family Rosaceae. Within the genus Aronia several species
and hybrids are known, such as Aronia melanocarpa (black
chokeberry), Aronia arbutifolia (red chokeberry), and Aronia x
prunifolia (purple chokeberry). The Aronia fruits are small pomes
and the juice of it is known to be astringent and to have a high
content of vitamin C and other antioxidants.
[0003] Due to their intensive fruit color Aronia is used as a
coloring agent for beverages and other food products, as disclosed
e.g. in U.S. Pat. No. 6,703,056, WO 2005 058052, and WO 2006
138419. Beside this, the Aronia fruits have awaken interest due to
their antioxidative qualities. For example Aronia melanocarpa is
known to have high contents of phenolic compounds, especially
anthocyanins, which are mainly located in the skin of the berries
for UV protection of the pulp and the seeds. These anthocyanins
give Aronia melanocarpa an extraordinary antioxidative strength. A
parameter showing the capacity of a compound or an extract to deal
with oxidative stress is the oxygen radical absorbance capacity or
ORAC. Aronia shows high ORAC values and is therefore also
used/added as a functional food or nutraceutical. For example, U.S.
2007 0020358 discloses a sports drink concentrate which may include
Aronia as a nutraceutical ingredient. A functional sweetener
composition comprising an Aronia extract as antioxidant is
disclosed in WO 2007 06 1900, and WO 2007 076857 teaches a chewing
gum composition containing Aronia which is used as a source of
antioxidants.
[0004] Further thereto, it is known from the prior art that Aronia
or compounds thereof may be used for the preparation of
pharmaceutical compositions or nutraceutical compositions and food
supplements. For example DE 10 2004 029 887 Al discloses a dietary
supplement on the basis of pomace comprising an extract of the skin
of Aronia fruits which dietary supplement is described to have a
high radical protection factor. DE 10 2004 052 882 A1 teaches a
dietary supplement on the basis of a specific selection of fruit
and legume concentrates, which comprises inter alia an Aronia fruit
juice concentrate. Said dietary supplement is described to
strengthen the immune system, wherein it is set forth that the
combination of ingredients synergistically influences the impact of
the ingredients.
[0005] WO 2001 015553 teaches that food supplements containing
Aronia fruit extract may be used to inhibit an inflammation
mediated by cyclooxygenase, i.e. it is disclosed that Aronia
extracts have an anti-inflammatory activity due to an inhibition of
COX-2 activity preferentially over COK-1 activity.
[0006] DE 10 2005 046 474 A1 teaches to use an extract of the
fruit's skin of Aronia sp. for the prophylactic and therapeutic
treatment of bacterial, mycotic and/or inflammatory
diseases/conditions. The effect achieved is attributed to an
antibacterial and antimycotic effect of said extract. A direct
influence of the extract on the immune system is not disclosed.
[0007] In addition thereto, WO 2002 005827 teaches the use of
Aronia extract for the preparation of a medicament for the
treatment of brain cancer and further discloses a nutraceutical
composition for the treatment of cancer comprising one or more
flavonoids from Aronia and the micronutrients selenium and
zinc.
[0008] Micronutrients are needed and involved, e.g. as cofactors
for enzymes, in a plurality of metabolism processes and are
therefore important ingredients in food. Accordingly, and as taught
by the prior art, micronutrients may be added to different kinds of
food for example to functional food in order to achieve or improve
certain physiological functions.
[0009] As regards the immune system, it is known that the
micronutrients selenium and zinc affect beside other physiological
functions the immune status. Selenium is known to be required for a
proper activity of neutrophils, macrophages, NK cells, T
lymphocytes and some other immune mechanisms and an insufficient
supply of selenium to the human body may result in a weakened
immune system. Zinc is known to be an important ion for enzymes,
proteins and transcription factors, and is therefore involved in
many functions of the body also including immune responses.
[0010] As already indicated above, combinations of an Aronia
extract with at least one micronutrient, in particular with
selenium and/or zinc, are known from the prior art. However, this
often seems to be a "combination by chance". For example WO 2005
058052 and WO 2006 138419 teach the use of Aronia as a coloring
agent, while zinc and selenium are comprised in a stabilizing
mixture for the food product taught in these references. In other
cases, the combination of Aronia extract with selenium and/or zinc
as taught in the prior art may be considered just as a consequence
of the purpose of the product. For example, the sports drink as
disclosed in U.S. 2007 0020358 teaches to use Aronia due to its
high ORAC value, while selenium and zinc are added as
micronutrients. Hence, these components are not taught in the prior
art to be combined in order to achieve a certain effect, which
results from the interrelated action of these components. In
particular, the prior art does not seem to indicate that due to the
selective combination of an Aronia extract with selenium and/or
zinc, a composition having an improved immune stimulating effect
may be obtained.
[0011] Even if different kinds of immune stimulating agents are
known, there is an ongoing need for improved immune stimulating
agents, since especially due to the increasing environmental stress
of modern life the immune system of human beings is continuously
exposed to various kinds of stress. Often agents based on a natural
or biological basis are preferred to synthetic pharmaceutical
products, because they are on the one hand often better accepted
from the patient or the consumer and may be also manufactured in a
more cost effective way, especially in the case when a plant
extract may be used per se, since no chemical synthesis and/or
purification of effective compounds is necessary.
[0012] Therefore, it is clear from the above that there is a need
for improved substances or compositions having immune stimulating
effects.
SUMMARY OF THE INVENTION
[0013] In the lines of extensive studies leading to the present
invention the inventors have found that particular micronutrients,
namely selenium, either alone or in combination with zinc, has an
advantageous effect on the beneficial effects of Aronia extracts.
It has been surprisingly found that an Aronia extract to which a
particular amount of selenium or selenium and zinc has been added
increases the macrophage activity by far in comparison to a
composition merely containing a natural Aronia extract. The
increased macrophage activity renders the present composition
particularly suitable for the treatment of inflammatory diseases or
conditions, bacterial infections, fungal infections, viral
infections, parasitic infections.
[0014] Hence the above problem has been solved by providing a
composition comprising an Aronia extract in an amount of at least
about 10 .mu.g/mg and selenium in an amount of from about 0.0001
.mu.g/mg to about 2.0 .mu.g/mg. It will be appreciated in this
context that according to the present invention selenium is added
to the Aronia extract. In other words, the amount of selenium or
the combination of selenium and zinc is beyond the natural
fluctuation range in an Aronia extract.
[0015] According to one embodiment the composition further
comprises additional zinc, preferably in a concentration from about
0.0001 mg/mg to about 0.5 mg/mg.
[0016] According to another embodiment the composition further
comprises at least one phai inaceutically or nutraceutically
acceptable excipient or a mixture thereof.
[0017] According to yet another embodiment the composition is
formulated as a pharmaceutical composition, preferably designed for
oral, such as peroral, buccal, sublingual, mucosal, or topical
administration.
[0018] According to yet another embodiment the composition is
formulated as a nutraceutical or supplementary neutraceutical
composition, preferably in the form of an ingestible solution or
suspension, comprising the active ingredient in dissolved or
suspended form, or as a solid administration form, such as in the
form of tablets, capsules, dragees, or added as a food supplement
to daily food products.
[0019] According to a further embodiment the composition according
to the present invention is for the preparation of a medicament,
preferably for the treatment of inflammatory diseases or
conditions, bacterial infections, fungal infections, viral
infections, parasitic infections and combinations thereof. The
inflammatory disease or condition is preferably associated with
autoimmune diseases, inflammatory bowel disease, multiple
sclerosis, scleroderma, and graft-versus-host disease.
SHORT DESCRIPTION OF THE FIGURES
[0020] FIGS. 1 and 2 shows evaluation of the optimal concentration
of Aronia extract on macrophage activity of macrophages of the
mouse leukaemic monocyte macrophage cell line RAW 264.7. It may be
seen that concentrations above approx. 40 .mu.g/ml decrease
macrophage activity.
[0021] FIG. 3 shows the immune stimulatory activity of selenium
employing macrophages of the cell line RAW 264.7. It may be seen
that concentrations above approx. 8 .mu.g/ml decrease macrophage
activity.
[0022] FIG. 4 shows the immune stimulating effect of a composition
according to the present invention by means of the activity of
macrophages of the cell line RAW 264.7 in dependence from the added
selenium concentration. The composition comprises an Aronia extract
in a concentration of 4.875 .mu.g/ml.
DETAILED DESCRIPTION OF THE PRESENT INVENTION
[0023] The present invention discloses a composition which
comprises a combination of an Aronia extract and the micronutrient
selenium. The composition may also comprise zinc as further
micronutrient, and is designed/ used for stimulating the immune
system.
[0024] According to the present invention the Aronia extract
originates from one Aronia species which is pharmaceutically and
nutraceutically acceptable or is a mixture of different
pharmaceutically/ nutraceutically acceptable Aronia species. Aronia
species that may be used include, but are not limited to A.
melanocarpa, A. arbutifolia, and A. x prunifolia. According to a
preferred embodiment of the present invention Aronia melanocarpa is
used.
[0025] The Aronia extract may be derived from the whole fruit or
from parts of the fruit. For example the extract may be produced on
the base of the pomace of the fruits. The Aronia extracts may be
obtained according to any suitable method known by a person skilled
in the art. The extract may be based on fresh fruits or dried
fruits or fruit juices. If desired, one or more particular active
compounds may be selectively enriched in the extract. An Aronia
extract may be obtained to the general knowledge of the skilled
person. Suitable ways for preparing an Aronia extract are for
example disclosed in DE 102004029887 and DE 102005046474. It will
be, however, appreciated that in principle each preparation of
plant extracts may be modified according to general knowledge in
order to obtain Aronia extracts suitable for the present invention.
General extraction methods for isolating plant material is for
example disclosed in FR 2892933 and Ljubuncic P. et al. (J.
Ethnopharmacol., Oct 3, 101(1-3) (2005), 153-61).
[0026] The Aronia extract may be prepared using whole fruits as
starting material. The fruits are washed with water of a
temperature between 30 and 50.degree. C., preferably of 40.degree.
C. and afterwards enzymatically treated with e.g. an inulinase,
preferably fructozyme, for partial or complete cell disruption.
Suitable enzymes as well as reaction conditions are well known to
the skilled person. The residue obtained after pressing is
extracted with aqueous potassium sulfite solution (approx. 10-30
w/v) for 1 to 3 hours at room temperature (approx. 21-24.degree.
C.). The extract is treated with pectin degrading enzymes, such as
pectinex or pectinol, at a pH of approx. 3-4, preferably pH 3, for
0.5-2 hours. Afterwards the extract is distilled under vacuum at a
temperature of around 40-58.degree. C., preferably 45-50.degree.
C., yielding Aronia extract having a residual water content of
approx. 30-40 w/w.
[0027] Alternatively, the Aronia extract may be prepared by means
of an ethanol extraction or it may be prepared as a dry
extract.
[0028] The composition according to the present invention comprises
the Aronia extract in a concentration from at least about 10
.mu.g/mg to about 990 .mu.g/mg, preferably from about 20 .mu.g/mg
to about 950 .mu.g/mg. Even more preferred from about 40 .mu.g/mg
to about 900 .mu.g/mg. Still more preferred is a concentration in
the range from about 50 .mu.g/mg to about 800 .mu.g/mg. Still even
more preferred is a concentration from about 60 .mu.g/mg to about
800 .mu.g/mg. Most preferably the Aronia extract is concentrated in
a range from about 80 .mu.g/mg to about 800 .mu.g/mg.
[0029] In a preferred embodiment a fluid composition of the present
invention comprises Aronia extract in a concentration of about 10
.mu.g/mg to about 200 .mu.g/mg, more preferred about 60 .mu.g/mg to
about 150 .mu.g/mg and most preferred about 80 .mu.g/mg.
[0030] In another preferred embodiment a solid or dried composition
of the present invention comprises Aronia extract in a
concentration of about 100 .mu.g/mg to about 990 .mu.g/mg, more
preferred from about 300 .mu.g/mg to about 800 .mu.g/mg, even more
preferred from about 400 .mu.g/mg to about 700 .mu.g/mg and most
preferred about 600 .mu.g/mg.
[0031] The values given are intended to mean the final
concentration of the Aronia extract in the composition according to
the present invention, i.e. the concentration with which the
extract is administered to a patient or a subject in need
thereof.
[0032] According to the present invention the composition also
comprises the micronutrient selenium. According to one embodiment
the composition comprises Aronia extract and a combination of the
micronutrients selenium and zinc. As used herein comprising a
micronutrient is intended to mean that additional amounts of said
micronutrient(s) is/are added in addition to the micronutrients
which may be already present in the Aronia extract. The Aronia
extract, particularly from the species Aronia melanocarpa, may
contain natural amounts of 4 mg/kg zinc and about 20 .mu.g/kg
selenium. It will be appreciated that these natural amounts may
vary dependent on the fruits specifies and growth conditions.
[0033] A recently performed analysis in a certified laboratory
revealed inter alia the following contents of metals in such an
Aronia extract (accuracy of the values.+-.20%):
TABLE-US-00001 TABLE 1 Metal Dimension Amount selenium mg/kg
<0.03 zinc mg/kg ~4.0
[0034] The micronutrient(s) selenium or selenium and zinc may be
provided for example, but not limited thereto as inorganic salts,
such as chlorides, sulfates, and the like, as organic salts and
other bioavailable forms, such as amino acid chelates or
combinations thereof. As used herein the terms "selenium" and
"zinc" are intended to comprise any compound containing selenium
and zinc, respectively, including salts, complexes or other forms
of said micronutrients, also including elemental selenium or zinc.
Acceptable forms of selenium and zinc are well known to the skilled
person. In case of given concentrations or ranges of concentrations
of said micronutrients said values are intended to indicate the
concentration of selenium or the selenium ion, and the
concentration of zinc or the zinc ion, respectively.
[0035] For example, but not limiting the present invention thereto
selenium may be provided as selenomethionine, elemental selenium,
various selenium salts, such selenium chloride, and selenium yeast
or combinations thereof According to a preferred embodiment of the
present invention selenium is provided as selenium yeast or sodium
selenite/ sodium selenate.
[0036] For example, but not limiting the present invention thereto
zinc may be provided as zinc acetate, zinc ascorbate, zinc
chloride, zinc citrate, zinc gluconate, zinc lactate, zinc
sulphate, amino acid chelated zinc, or combinations thereof.
According to a preferred embodiment of the present invention zinc
is provided as zinc chloride.
[0037] The composition according to the present invention may be
provided in liquid form or in dried/solid form, e.g. in a
lyophilized form. According to a preferred embodiment of the
present invention the composition is provided in a sterile
form.
[0038] During the extensive studies leading to the present
invention, it has been surprisingly found that a composition
comprising an Aronia extract and additionally added selenium or
additionally added selenium and zinc has an enhanced immune
stimulating effect in comparison to the single compounds of the
composition according to the present invention. Without wishing to
be bound to any theory it seems that the beneficial immune
stimulating effect of the composition according to the present
invention is based on a synergistic effect of the complex mixture
of compounds comprised in the Aronia extract in combination with
the additionally added selenium. A further synergistic effect may
be achieved when adding zinc to the composition comprising Aronia
extract and selenium.
[0039] In particular, the composition according to the present
invention has been shown to increase the macrophage activity.
Macrophages belong to the innate immune system which is e.g.
responsible for destroying virus infected cells, parasites and
tumour cells. Macrophages represent matured monocytes, which in
turn belong to the white blood cells. Macrophages phagocytose and
digest invading microorganisms, even protozoa, debris, foreign
bodies as well as damaged, dead and senescent cells.
[0040] Accordingly the composition according to the present
invention can be used to stimulate the immune system. In
particular, the composition according to the present invention may
be used for the preparation of a medicament for the treatment of a
variety of diseases or conditions which are based on a reduced
activity of the immune system, or which may be prevented or treated
by stimulating the immune system. In particular, diseases or
conditions may be treated or prevented that are based on a reduced
macrophage activity or which may be prevented or treated by
enhancing the macrophage activity.
[0041] Within the present invention treatment is intended to mean
prophylactic or therapeutic treatment, wherein the therapeutic
treatment may be palliative or curative.
[0042] Since the composition according to the present invention is
characterized by an immune stimulating activity it may be also used
for the preparation of a medicament designed for adjuvant therapy
during the treatment of diseases which treatment is beneficially
affected by stimulating the immune system. Furthermore, the
composition according to the present invention may also be used for
the preparation of a dietary supplement for supporting the immune
system.
[0043] According to one embodiment of the present invention the
composition is designed for the treatment of inflammatory diseases
or conditions, bacterial infections, fungal infections, viral
infections, parasitic infections and combinations thereof.
[0044] In particular the composition may be used for alleviate or
improving any disorder or disease including but not limited to
septic shock, haemodynamic shock, sepsis syndrome, post ischaemic
reperfusion injury, inflammatory bowel disease, graft-versus-host
disease, malaria, mycobacterial infection, meningitis, psoriasis,
congestive heart failure, fibrotic diseases, cachexia, graft
rejection, cancers such as cutaneous T-cell lymphoma, diseases
involving angiogenesis, autoimmune diseases, skin inflammatory
diseases, inflammatory diseases of the eye, inflammatory bowel
diseases such as Crohn's disease and colitis, osteo- and rheumatoid
arthritis, ankylosing spondylitis, psoriatic arthritis, adult
Still's disease, uveitis, Wegener's granulomatosis, Behcet disease,
Sjoegren's syndrome, sarcoidosis, conjunctivitis, polymyositis,
dermatomyositis, multiple sclerosis, sciatica, complex regional
pain syndrome, radiation damage, hyperoxic alveolar injury,
periodontal disease, HIV, non-insulin dependent diabetes mellitus,
systemic lupus erythematosus, glaucoma, idiopathic pulmonary
fibrosis, bronchopulmonary dysplasia, retinal disease, scleroderma,
osteoporosis, renal ischemia, myocardial infarction, cerebral
stroke, cerebral ischemia, nephritis, hepatitis,
glomerulonephritis, cryptogenic fibrosing aveolitis, psoriasis,
transplant rejection, atopic dermatitis, vasculitis, allergy,
seasonal allergic rhinitis, reversible airway obstruction, adult
respiratory distress syndrome, asthma, chronic obstructive
pulmonary disease (COPD) and/or bronchitis. In addition, wound
healing may be facilitated.
[0045] Examples of bacterial or microbial infections comprise any
infection with gram positive or gram negative bacteria.
Pathological conditions of microbial infections which can be
treated or prevented by the present compositions include, but are
not limited to, conditions such as chronic upper respiratory
disease, wound infection, osteomyelitis, endocarditis, skin
polymicrobial infections, bronchial asthma, chronic sinusitis,
cystic fibrosis or acne vulgaris.
[0046] Examples of fungal infections include for example
blastomycosis, coccidiodomycosis, cryptococcosis, histoplasmosis,
sporotrichosis, chromoblastomycosis, lobomycosis, dermatophytosis,
derniatomycosis, onychomycosis, piedra, mycetoma, fusariosis,
pityriasis versicolor, tinea barbae, tinea capitis, tinea corporis,
tinea cruris, tinea favosa, tinea nigra, tinea pedis,
phaeohyphomycosis, rhinosporidiosis, aspergillosis, mycotic
keratitis, candidiasis.
[0047] Viral infections to be treated may be caused by viruses
including, but not limited to, lentiviruses such as human
immunodeficiency virus types 1 and 2 (HIV), human T-cell
lymphotropic virus type 1 and 2 (HTLV-I and HTLV-II), SIV, EIAV
(equine infectious anemia virus), BIV, FIV, CAEV, VMV, and MMLV
(Moloney murine leukemia virus). Such viral infections can also be
caused by hepatitis A virus, hepatitis B virus, hepatitis C virus,
hepatitis D virus, hepatitis E virus, hepatitis G virus, human
foamy virus, or by human herpes viruses (e.g., herpes simplex virus
type-1, herpes simplex virus type-2, herpes simplex virus type-3
(also known as Varicella-zoster virus), herpes simplex virus type-4
(also known as Epstein Barr virus or EBV), herpes simplex virus
type-5, herpes simplex virus type-7). Such viral infections can
also be caused by influenza viruses (types A, B or C), human
parainfluenza viruses, respiratory syncytial virus, smallpox virus
(variola virus), monkeypox virus, vaccinia virus, human papilloma
virus, human parechovirus 2, mumps virus, Measles virus, Rubella
virus, Semliki Forest virus, West Nile virus, Colorado tick fever
virus, foot-and-mouth disease virus, Ebola virus, Marburg virus,
polyomavirus, TT virus, Lassa virus, lymphocytic choriomeningitis
virus, vesicular stomatitis virus, rotavirus, varicella virus,
parvovirus, cytomegalovirus, encephalitis viruses, adenovirus,
echovirus, rhinoviruses, filoviruses, coxachievirus, coronavirus
(such as SARS-associated coronavirus), Dengue viruses, yellow fever
virus, hantaviruses, regional hemorrhagic fever viruses, molluscum
virus, poliovirus, rabiesvirus, etc.
[0048] Examples of parasitic infections include but are not limited
to malaria. Parastic infections may be caused by organisms such as
protozoa, helminths, and ectoparasites.
[0049] According to the present invention selenium is added as a
micronutrient to the composition comprising Aronia extract.
Selenium is added in one or more suitable form(s) as set forth
above.
[0050] During the extensive studies leading to the present
invention it was surprisingly found that the beneficial effect,
i.e. the immune stimulating effect, of selenium which is added to
the Aronia extract is dependent on the added selenium
concentration.
[0051] According to the present invention selenium is added to the
composition to a final concentration from about 0.0001 .mu.g/mg to
about 2.0 .mu.g/mg. Preferably, selenium may be added to the
composition in a range from about 0.0005 .mu.g/mg to about 1.0
.mu.g/mg. Even more preferred from about 0.001 .mu.g/mg to about
0.5 .mu.g/mg. Still more preferred is a concentration ranging from
about 0.001 .mu.g/mg to about 0.25 .mu.g/mg. Even still more
preferred is a concentration ranging from about 0.001 .mu.g/mg to
about 0.2 .mu.g/mg. Most preferred is a concentration between about
0.0012 .mu.g/mg to about 0.1 .mu.g/mg.
[0052] According to a preferred embodiment a fluid composition of
the present invention comprises selenium in a concentration from
about 0.0001 .mu.g/mg to about 0.01 .mu.g/mg, more preferably from
about 0.0005 .mu.g/mg to about 0.005 .mu.g/mg, most preferably from
about 0.0008 .mu.g/mg to about 0.003 .mu.g/mg and even most
preferably about 0.0012 .mu.g/mg.
[0053] In another preferred embodiment a solid or dried composition
of the present invention comprises selenium in a concentration from
about 0.001 .mu.g/mg to about 0.5 .mu.g/mg, more preferably from
about 0.005 .mu.g/mg to about 0.01 .mu.g/mg, most preferably from
about 0.003 .mu.g/mg to about 0.02 .mu.g/mg and even most
preferably about 0.01 .mu.g/mg.
[0054] The values given are intended to mean the final
concentration of added selenium in the composition according to the
present invention, i.e. the concentration with which the added
selenium is administered to a patient or a subject in need
thereof.
[0055] The final concentration of selenium added to the composition
according to the present invention may be chosen also in view of
the daily requirement amounts of selenium. Accordingly, factors
like for example the intended way of administration, and the
amount/dosage of the composition given per day and subject, may be
considered. Such considerations are within the general knowledge of
the skilled person.
[0056] According to a preferred embodiment of the present invention
zinc may be added to the composition comprising Aronia extract and
selenium, in one or more suitable forms as set forth above, to
formulate a composition according to the present invention.
[0057] Zinc may be added to the composition of the present
invention in a concentration from about 0.0001 mg/mg to about 0.5
mg/mg. Preferably, zinc may be added to the composition in a range
from about 0.0005 mg/mg to about 0.1 mg/mg. Even more preferred
from about 0.001 mg/mg to about 0.08 mg/mg. Still more preferred is
a concentration ranging from about 0.0015 mg/mg to about 0.006
mg/mg. Even still more preferred is a concentration ranging from
about 0.002 mg/mg to about 0.04 mg/mg.
[0058] The values given are intended to mean the final
concentration of the added zinc in the composition according to the
present invention, i.e. the concentration with which the added zinc
is administered to a patient or a subject in need thereof.
[0059] The final concentration of zinc added to the composition
according to the present invention may be selected also in view of
the daily requirement amounts of zinc. Accordingly, factors like
for example the intended way of administration and the
amount/dosage of the composition given per day and subject, may be
considered. Such considerations are within the general knowledge of
the skilled person.
[0060] As regards the concentrations with which selenium and zinc
are added to the composition according to the present invention,
each of the micronutrients may be added in a concentration or a
concentration range as given above
[0061] The composition according to the present invention may be
administered by itself, for example in liquid or in solid form, or
may be formulated as pharmaceutical composition or as nutraceutical
composition.
[0062] Said pharmaceutical composition or nutraceutical composition
comprises as an active ingredient a composition according to the
present invention and at least one pharmaceutically/
nutraceutically acceptable excipient or a mixture of
pharmaceutically/nutraceutically acceptable excipients. Suitable
excipients include, but are not limited to diluents, carriers,
disintegrants, binders, glidants, lubricants, coating agents and
the like or mixtures thereof, which might be needed for the
preparation of final dosage forms. The pharmaceutical or
nutraceutical compositions according to the present invention may
be prepared by mixing the active ingredient, optionally in
combination with other active compounds, with one or more suitable
excipient(s) by methods which are well known to the skilled person.
Preferably, the pharmaceutical or nutraceutical compositions are
prepared under sterile conditions.
[0063] The pharmaceutical composition or nutraceutical composition
according to the present invention may comprise from about 1% to
about 99% by weight of said pharmaceutically acceptable
excipient(s), preferably from about 10% to about 95% by weight, and
most preferably from about 20% to about 75% by weight.
[0064] The selection of one or more appropriate excipient(s) and
their respective amounts is within the general knowledge of the
skilled person. The excipient(s) may be selected with regard to the
intended route of administration.
[0065] The pharmaceutical or nutraceutical compositions according
to the present invention may be formulated in a variety of ways to
be administered to humans and/or animals. The pharmaceutical or
nutraceutical composition according to the present invention may be
formulated in a liquid form, i.e. for example in the form of
solutions, dispersions, emulsions and gels, or in a solid form. The
pharmaceutical composition as well as the nutraceutical composition
may be designed for immediate release and/or for sustained release.
Accordingly, also depot forms of the composition according to the
present invention are within the scope of the present
invention.
[0066] According to one preferred embodiment of the present
invention the composition is formulated as a pharmaceutical
composition. Said pharmaceutical composition comprises a
therapeutically effective amount of a composition according to the
present invention together with one or more pharmaceutically
acceptable excipient(s). A therapeutically effective amount of a
composition according to the present invention is an amount that
when administered to a patient or a subject in need thereof is
capable of exerting an immune stimulating effect. In particular,
said effective amount is capable of increasing the macrophage
activity.
[0067] By way of example, but without limiting the present
invention thereto, a pharmaceutical composition according to the
present invention may be formulated for .sub.[c1]oral, such as
peroral, buccal, sublingual, or mucosal administration, or for
topical administration.
[0068] According to a preferred embodiment of the pharmaceutical
composition of the present invention, said pharmaceutical
composition is designed for oral administration. Such a
pharmaceutical composition may be designed as an ingestable
solution or suspension, comprising the active ingredient in
dissolved or suspended form, or as a solid administration form,
such as for example tablets, capsules, dragees, powders,
granules.
[0069] According to another preferred embodiment of the
pharmaceutical composition of the present invention, said
pharmaceutical composition is designed for topical administration.
Topical administration may be achieved for example, but not
limiting the present invention thereto, in the form of ointments,
creams, lotions, solutions, and elixirs.
[0070] Moreover, since the action of the composition according to
the present invention is based on a stimulation of the individual's
own immune system, said composition may well be used for the
preparation of a nutraceutical composition designed for stimulating
the immune system, in particular by increasing the macrophage
activity. Therefore, and in accordance with another preferred
embodiment of the present invention the composition is formulated
as a nutraceutical composition.
[0071] As used herein, a nutraceutical composition is intended to
mean a composition that may be considered as food or a food
supplement, which is used to improve the diet in order to provide
well-being, health benefits and to help to prevent diseases and
infections by stimulating the individual's own immune system.
[0072] A pharmaceutical/ nutraceutical composition according to the
present invention comprises an effective amount of a composition
according to the present invention together with one or more
pharmaceutically/ nutraceutically acceptable excipient(s). An
effective amount of a composition according to the present
invention is an amount that when administered to a subject in need
thereof is capable of exerting an immune stimulating effect.
[0073] By way of example, but without limiting the present
invention thereto, a nutraceutical composition according to the
present invention may be formulated for oral, such as peroral,
buccal, sublingual, or mucosal administration.
[0074] According to a preferred embodiment of the nutraceutical
composition according to the present invention, said nutraceutical
composition is designed for oral administration. A nutraceutical
composition for oral administration may be designed as an
ingestable solution or suspension, comprising the active ingredient
in dissolved or suspended form, or as a solid administration form,
such as in the form of tablets, capsules, dragees.
[0075] The nutraceutical composition according to the present
invention may be formulated to be added as a food supplement to
daily food products. For example, the nutraceutical composition may
be added to beverages, cereals, etc.
[0076] It will be appreciated that the amount to be administered
depends on the subject to be treated taking into account its age,
weight and other personal conditions.
[0077] The present invention will now be described by way of
specific examples which are only for illustration and which are not
intended to limit the scope of the present invention. Various
modifications and changes can be made without departing from the
scope of the present invention which is set forth in the appended
claims.
EXAMPLES
Preparation of the Aronia Extract
[0078] Fresh-frozen Aronia fruits (chokeberries) have been used for
preparing the Aronia extract (botanical species: Aronia
melanocarpa). The aqueous pressed juice was concentrated to obtain
a ratio of fruits to pressed juice concentrate (native) of 8-10 to
1.
Effect of the Aronia Extract and Aronia Extract with a
Micronutrient on Macrophage Activity
[0079] Cells: Cell line (RAW 264.7, murine macrophages) was
purchased from the America Type Culture Collection and cultivated
as recommended.
[0080] Chemiluminescence Assay: Lucigenine (Sigma Chemicals Co.)
was dissolved in Hank's Balanced Salt Solution (HBSS; Gibco Co.) at
a concentration of 2.times.10.sup.-3 M. This stock solution was
further diluted in HBSS prior to use. 1 ml cells (5.times.10.sup.6
cells/ml) were incubated with 0.1 ml solution of Aronia extract and
Aronia extract together with sodium selenite (dosis kinetics for
each component and the combinations as documented in the figures).
All these constituents were kept in an incubator (37.degree. C., 5%
CO.sub.2) for 30 min, then centrifuged at 1200 U/min for 5 min and
resuspended in minimal essential medium (MEM, Gibco Co.).
[0081] The reaction mixture consisted of a suspension (0.25 ml) at
a concentration of 5.times.10.sup.6 PMNL (polymorphonuclear
leucocytes)/ml respectively monocytes/macrophages, 50 .mu.l
zymosan, and 0.45 ml medium containing 2.times.10.sup.-6 M
lucigenine. The reaction mixture was kept at 37.degree. C. before
chemoluminescence measurements were performed with a Luminometer
(Luminoskan 1251, Labsystems) according to manufacturer's
instructions (User's Manual 1995).
* * * * *