U.S. patent application number 11/997555 was filed with the patent office on 2008-12-11 for marrubiin and composition for reducing snoring, package and method.
This patent application is currently assigned to PURANOX MEDICAL B.V.. Invention is credited to Hans Marcel Brand, Annelize Frieda Goedbloed.
Application Number | 20080305192 11/997555 |
Document ID | / |
Family ID | 36685949 |
Filed Date | 2008-12-11 |
United States Patent
Application |
20080305192 |
Kind Code |
A1 |
Brand; Hans Marcel ; et
al. |
December 11, 2008 |
Marrubiin and Composition For Reducing Snoring, Package and
Method
Abstract
The invention comprises a composition for the reduction of
snoring, a packaging therefor and a method for the manufacture
hereof. The composition can be applied in the pharynx in different
variants, in particular as spray, as gel or as foam formulation.
Application of the composition at least temporarily reduces the
snoring of a treated person. The invention further comprises the
use of marrubiin for the manufacture of a medication for the
treatment of snoring.
Inventors: |
Brand; Hans Marcel; (
Nieuwerkerk a/d IJssel, NL) ; Goedbloed; Annelize
Frieda; (Delft, NL) |
Correspondence
Address: |
DeMont & Breyer, LLC
100 Commons Way, Ste. 250
Holmdel
NJ
07733
US
|
Assignee: |
PURANOX MEDICAL B.V.
NL-4904 SX Oosterhout
NL
|
Family ID: |
36685949 |
Appl. No.: |
11/997555 |
Filed: |
August 4, 2006 |
PCT Filed: |
August 4, 2006 |
PCT NO: |
PCT/NL2006/050194 |
371 Date: |
May 13, 2008 |
Current U.S.
Class: |
424/756 ;
424/725 |
Current CPC
Class: |
A61P 43/00 20180101;
A61K 36/53 20130101; A61K 2300/00 20130101; A61K 36/53 20130101;
A61P 11/00 20180101 |
Class at
Publication: |
424/756 ;
424/725 |
International
Class: |
A61K 36/906 20060101
A61K036/906; A61K 36/53 20060101 A61K036/53 |
Foreign Application Data
Date |
Code |
Application Number |
Aug 5, 2005 |
NL |
1029684 |
Claims
1. Composition for reducing snoring, comprising at least an active
quantity of at least one active component with astringent
properties and a physiologically acceptable excipient.
2. Composition as claimed in claim 1, characterized in that the
composition is substantially liquid.
3. Composition as claimed in claim 1, characterized in that the
composition is a gel.
4. Composition as claimed in claim 1, characterized in that the
composition is a foam.
5. Composition as claimed in claim 1, characterized in that at
least one active component with astringent properties is white
horehound.
6. Composition as claimed in claim 1, characterized in that at
least one active component with astringent properties is black
horehound.
7. Composition as claimed in claim 1, characterized in that the
composition comprises white horehound and black horehound in active
quantities.
8. Composition as claimed in claim 7, characterized in that the
ratio of the percent by mass of white horehound to the percent by
mass of black horehound lies between 1:10 and 10:1.
9. Composition as claimed in claim 8, characterized in that the
ratio of the percent by mass of white horehound to the percent by
mass of black horehound lies between 1:2 and 2:1.
10. Composition as claimed in claim 7, characterized in that the
percent by mass of white horehound is substantially equal to the
percent by mass of black horehound.
11. Composition as claimed in claim 7, characterized in that the
composition also comprises at least one flavouring.
12. Composition as claimed in claim 11, characterized in that the
flavouring is selected from the group consisting of peppermint,
aniseed and eucalyptus.
13. Composition as claimed in claim 5, characterized in that the
composition also comprises ginger.
14. Composition as claimed in claim 5, characterized in that the
composition also comprises thyme.
15. Composition as claimed in claim 1, characterized in that the
active components form 0.1-10% by weight of the composition.
16. Composition as claimed in claim 1, characterized in that the
composition also comprises an active quantity of osmosis
regulator.
17. Composition as claimed in claim 16, characterized in that the
osmosis regulator substantially comprises betaine.
18. Composition as claimed in claim 1, characterized in that the
composition comprises 1 to 20% by weight of a permeabilizer.
19. Composition as claimed in claim 1, characterized in that the
composition comprises between 0.5 and 5% by weight of xylitol.
20. Composition as claimed in claim 1, characterized in that the
composition also comprises 0.01-5% by weight of bio-adhesive
gelling agent.
21. Composition as claimed in claim 1, characterized in that the
composition also comprises 0.01-2% by weight of surfactant.
22. Packaging comprising a composition as claimed in claim 1,
wherein the packaging is provided with dosing means adapted for
oral administration of the composition.
23. Packaging as claimed in claim 22, characterized in that the
dosing means comprise guide means adapted to guide the composition
to the pharynx of a person for treating.
24. Packaging as claimed in claim 22, characterized in that the
package comprises a container which comprises a propellant in
addition to the composition.
25. Packaging as claimed in claim 24, characterized in that the
propellant is held in a flexible vessel in the container.
26. Packaging as claimed in claim 22, characterized in that the
package is provided with a valve adapted for placing between the
lips.
27. Packaging as claimed in claim 22, characterized in that the
package is provided with a spout for guiding the composition to the
pharynx.
28. Method for manufacturing a composition for the treatment of
snoring as claimed in claim 1, the method comprising mixing at
least one active component with astringent properties and a
physiologically acceptable excipient.
29. A method for manufacturing a medication for the treatment of
snoring, the method comprising utilizing marrubiin.
Description
[0001] The invention comprises a composition for the purpose of
reducing snoring. The invention further relates to a package
comprising such a composition. The invention furthermore relates to
a method for manufacturing such a composition. The invention also
comprises the use of marrubiin for the production of a medicine for
the treatment of snoring.
[0002] Snoring is the production during sleep of snorting, wheezing
and/or grunting sounds during breathing. During breathing air is
carried through the nose and/or oral cavity from and to the lungs
via the throat and the windpipe. It is generally assumed that
vibrations of tissue in the area of the pharynx are caused by the
displacement of air during inhaling and exhaling, particularly in
the region around the uvula and/or the vocal cords. In addition to
natural predisposition, age and disorders of the oral cavity and/or
pharynx, snoring is associated with, among others, use of alcohol,
smoking and being overweight. The noise nuisance caused by snoring
can adversely affect the sleep of other people.
[0003] The present invention has for its object to provide means
with which snoring of a person can be reduced.
[0004] The invention provides for this purpose a composition for
reducing snoring, comprising at least an active quantity of at
least one active component with astringent properties and a
physiologically acceptable excipient. Such a composition is
preferably applied in the pharynx. Treatment with the composition
according to the invention is found, surprisingly, to suppress the
sounds of snoring, or at least reduce them to an acceptable level,
and in some cases to even obviate them completely. The composition
according to the invention can be applied usefully not only in the
domestic domain but also in professional situations where a
plurality of people must necessarily sleep in the same space, such
as in a dormitory, a hospital or military barracks.
[0005] It is currently assumed that a single administration of the
agent according to the invention at the beginning of the night will
provide sufficient effect for the night. It cannot however be
precluded that the effect diminishes after a period of time and
that a new dosage of composition must be applied.
[0006] A possible explanation for the effect is that the astringent
(contracting) properties of the active component or active
components make the treated tissue stiffer, whereby the vibrations
which cause the snoring sounds are no longer possible while the
composition is active. Astringent properties are particularly
understood to mean that the component applied to mucous membrane
brings about a contraction of tissue at the treated location.
[0007] The physiologically acceptable excipient can be any
appropriate, pharmaceutically acceptable matrix suitable for use in
pharynx and oral cavity, in the form of a solid, liquid or mixture
thereof. The active component can be for instance an essential oil
or hydro-alcoholic botanical extract.
[0008] The mucous membrane of the oral cavity, pharynx and nasal
passage to which the composition is applied is constantly producing
mucus. A person will also swallow regularly, whereby the active
component is also removed from the treatment location. The applied
composition will thus disappear after a period of time and can
therefore only act on the mucous membrane for a limited time.
[0009] It is advantageous if the composition is substantially
liquid. Such a composition is simple to apply at the desired
location in for instance the pharynx. A liquid composition
furthermore distributes the active component properly over the
surface to be treated. The liquid composition can be for instance a
solution, an emulsion or a dispersion A liquid excipient, such as
water, an aqueous solution or a mixture of different liquids can be
used for a liquid composition. A liquid composition can for
instance be used as gargle in order to apply the active component
to the desired location.
[0010] The liquid composition is preferably sprayable. A sprayable
composition has a viscosity of less than 10,000 cPs, preferably
less than 5000 cPs at body temperature. Such a solution can be
administered using a suitable spray device. Particularly
advantageous is a composition with a viscosity between 1000 cPs and
10000 cPs, preferably between 1000 and 5000 cPs. Such a composition
combines a good contact time at the treated location with an
efficient absorption of the active component. The active component
can thus be applied in even more efficiently distributed manner. It
is particularly recommended that the composition be sprayable as an
aerosol, wherein a liquid is converted into a very finely
distributed mist. Such a very finely distributed mist gives an even
more efficient use of the composition, and is absorbed very well.
The aerosol can be generated by a container with a propellant, but
also by a container with a venturi spray unit.
[0011] In a preferred embodiment the composition is a gel. A gel is
a liquid with an increased viscosity relative to water. Usable
gel-forming excipients are generally macromolecular products which
bind water. The gel preferably has a viscosity greater than 1000
cPs at body temperature. A gel provides for a longer contact time
of the active component at the desired location, and results in a
more efficient use of the active component and an improved
effectiveness. A gel can be manufactured by adding at least one
gel-forming excipient to the composition, although it is also
possible to envisage the active component itself forming a gel.
Usable gel-forming excipients are for instance, though not limited
to, vegetable exudates such as karaya gum, tragacanth gum, arabic
gum, ghatti gum, polysaccharides obtained from seeds such as guar
gum, carob bean flour, tamarind gum, polysaccharides from seaweed,
such as carrageenan, alginates, alginic acid, extracellular
microbiological polysaccharides such as xanthan gum and dextran,
starch products such as maltodextrin, maca, konjac mannan, maize
starch, animal products such as casein, gelatin, keratin, cellulose
derivatives such as methylcellulose, hydropropyl methylcellulose,
hydroxypropyl cellulose, hydroxyethyl cellulose, copolymers of
ethylene and propylene oxide, macromolecules derived from acrylic
acid and/or methacrylic acid, and macromolecules derived from vinyl
alcohol. For the formation of a suitable gel from such components
reference is made to D. Laba, Rheological Properties of Cosmetics
and Toiletries, Marcel Dekker, 1993, ISBN 0-8247-9090-1.
[0012] It is advantageous if the composition is a foam. A foam
gives a highly improved distribution of the active component over
the treated surface. A surface-active substance is necessary in
order to make a foam. Surface-active substances reduce the surface
tension of water and are always products made up of a hydrophilic
(lipophobic) portion and a lipophilic (hydrophobic) portion. The
surface-active substance/combination of surface-active substances
can form part of the group of non-ionic, anionic, cationic of
amphoteric surface-active substances. For specific components, to
the extent they are suitable for use in the oral cavity and
pharynx, reference is made to M. M. Rieger, Surfactant
Encyclopedia, Allured Publishing Corp, ISBN #0-931710-49-9.
[0013] In a preferred embodiment at least one active component with
astringent properties is white horehound. The etheric oil and/or
extracts thereof are found to have particularly favourable effects
on the level of snoring of a treated person. White horehound is
known as marrubium vulgare (Marrubium vulgare; UK: White Horehound,
DE: Andorn, FR; Marrube). White horehound contains a wide variety
of physiologically active products such as flavonoids, substittied
cinnainic acids such as caffeinic acid, terpenoids,
osmosis-regulating products such as turicine and betonicine and
pentacyclic steroids. In addition to the above-mentioned substances
present in white horehound, a typical component of marrubium
vulgare is the substance marrubiin, wherein marrubiin can also be
present in the form of the derivatives marrubenol and
marrubiol.
[0014] In another preferred embodiment at least one active
component with astringent properties is black horehound. This plant
and its hydrophilic extract and/or the etheric oil arc also found
to have particularly favourable effects on the level of snoring of
a treated person. Black horehound is known as ballota nigra
(Ballota nigra; UK: black horehound, FR: Ballotte fetide, DE:
Gottvergess). Black horehound comprises an etheric oil consisting
of flavonoids such as tangeritin, mono- and sesquiterpenoids in
addition to specific typical components such as ballonigrin,
ballotenol and ballotinone. These products are structurally related
to marrubiin and are characterized as furanoid sesquiterpenoids (G.
Savona, F. Piozzi, J. R. Hanson, M. Siverns, J. Chem. Soc., Perkin
Trans., 5,497,1977).
[0015] It is advantageous if the composition comprises both white
horehound and black horehound in active quantities. In combination
with white horehound, black horehound is found to have a
synergistic effect for suppressing snoring. Favourable mixtures
comprise white horehound and black horehound in a mass ratio of
between 1:25 and 25:1. The ratio here indicates the mass ratio of
the etheric oils of respectively white horehound and black
horehound.
[0016] The ratio of the percent by mass of white horehound to the
percent by mass of black horehound preferably lies between 1:10 and
10:1. At such a percentage the synergistic action of the two active
components is particularly efficient. The ratio of the percent by
mass of white horehound to the percent by mass of black horehound
more preferably lies between 1:2 and 2:1. The percent by mass of
white horehound is most preferably substantially equal to the
percent by mass of black horehound.
It is favourable if the composition also comprises at least one
flavouring. A flavouring camouflages the taste of the combination
of white horehound and black horehound, which is perceived by many
people as unpleasant and bitter.
[0017] It is recommended here that the flavouring is selected from
the group consisting of peppermint, aniseed and eucalyptus. These
flavourings are found to be the most effective in camouflaging the
taste of the combination of white horehound and black horehound. A
combination of a plurality ofthese flavourings is also
effective.
[0018] When multiple active components with astringent effect are
used, an active quantity is understood to mean the quantity of all
active components. The active components can therefore be present
in concentrations in which they would not be individually active
but which, in combination with the other components in the given
concentrations, do achieve the desired effect.
[0019] It is advantageous if the composition also comprises ginger.
Ginger can for instance be added as extract or etheric oil. The
best-known form of ginger is Zingiber officinale, although other
types have a comparable effect. An improved anti-snoring effect is
obtained with ginger in combination with white horehound and/or
black horehound. 20 to 60% by weight of the active components
preferably consist of ginger. Such a composition moreover has a
greatly improved taste, whereby a treated person perceives the
treatment as pleasant and treatment with the composition can be
followed with greater success.
[0020] It is recommended that the composition also comprises thyme.
Such a composition gives an improved anti-snoring effect. The
best-known form of thyme is known as Thymus vulgaris. Thyme can be
incorporated as oil and/or extract in the composition. Thyme gives
an improved anti-snoring effect.
It is recommended that the active components form 0.1-10% by weight
of the composition, preferably 0.5-8% by weight of the formulation,
more preferably 1-5% by weight. In such a concentration a good
anti-snoring effect is realized, wherein the active components are
moreover used efficiently. A part of the effective component is
after all removed from the desired location after a time by the
production of mucus by the mucous glands in combination with
swallowing, and can therefore only act on the treated location for
the limited contact time. At higher concentrations a large part of
the active component is in fact not used to achieve the
anti-snoring effect, and this is in fact a waste of the often
relatively expensive active components. At the stated
concentrations it is possible to apply the active component in well
distributed manner so that it can act sufficiently on the mucous
membrane at the treated location during the contact time.
[0021] The composition preferably also comprises an active quantity
of osmosis regulator. Addition of an osmosis regulator is found to
improve the anti-snoring effect of the composition. The best
anti-snoring results are achieved with formulations comprising
between 0.1 and 10% by weight of osmosis regulator, depending on
the matrix used. It is possible here to use a combination of
different substances as osmosis regulator. Osmosis regulators are
products which are responsible for the intercellular transport of
water (E.E. Brand-Garnys, H.M. Brand, Soap, Perfumery and
Cosmetics, 2005).
Excessive water transport results in slackening of the tissue,
which encourages snoring, and this is prevented by the osmosis
regulator. Osmosis regulators which can be used are betaine
(trimethylglycine) and related amino acid betaines such as alanine
betaine, dimethylsulfoniopropionate (DMSP;
S,S-dimethyl-3-mercaptopropionic acid), choline sulfate, proline
and hydroxyproline, betaine, ectoine, some polyoles such as
glycerol and non-reducible sugars such as trehalose, mannitol and
inositol.
[0022] In a preferred embodiment the osmosis regulator
substantially comprises betaine. Addition of betaine as osmosis
regulator is found to give improved anti-snoring results as well as
an improved sensation when administered orally. This could be
because betaine improves the absorption of the active component at
the treated location. The systematic name of betaine is
trimethylglycine (TMG).
It is advantageous if the composition comprises 1 to 20% by weight
of apermeability enhancer. A permeability enhancer accelerates the
absorption of the active component by the treated tissue, and
thereby the effectiveness of the formulation. Ethanol, dimethyl
sulfoxide (DMSO), phytantriol and methyl sulfonyl methane (dimethyl
sulfone; MSM), or mixtures thereof are particularly useful as
permeability enhancer.
[0023] The composition preferably also comprises at least one
flavouring. Using the flavouring the taste of the composition can
be improved, whereby a treated person perceives the treatment as
being more pleasant. The flavouring is preferably an etheric oil or
a mixture thereof. At least one flavouring is preferably chosen
from the group consisting of eucalyptus oil, menthol, oil of
cloves, aniseed oil and peppermint oil. Other etheric oils can also
be envisaged, such as sweet orange oil, pine oil, grapefruit oil
and mandarin oil. These substances cause a fiesh and tasty
sensation in the mouth and throat. Combinations of multiple types
of flavouring can be envisaged. The flavouring generally comprises
between 0.01 and 5% by weight of the formulation, depending on the
type of flavouring and the desired strength. The frequently bitter
or otherwise less agreeable taste of the active component is thus
camouflaged in effective manner. This is particularly advantageous
if the composition comprises thyme, the bitter taste of which can
be camouflaged by flavourings.
[0024] It is advantageous that the composition comprises between
0.5 and 5% by weight of xylitol. Xylitol has an antibacterial
action, whereby the user of the composition has relatively fresh
breath once the active duration has ended. In addition, xylitol
also acts as sweetener, thereby enhancing the taste of the
composition.
[0025] The composition preferably also comprises 0.01-5% by weight
of bio-adhesive gelling agent. A longer contact time of the
composition at the desired location is hereby obtained At high
concentrations of gelling agent (0.05-5% by weight) a gel is
obtained with high viscosity, this likewise contributing toward an
increased contact time at the treated location. Gelling agents with
bio-adhesive properties that can be used comprise for instance
hydroxypropyl methylcellulose, xanthan gum, karaya gum, tragacanth
gum, carrageenan, mannan gum and chitosan.
It is advantageous when the composition also comprises 0.01-2% by
weight of surfactant A surfactant is a surface-active substance and
contributes toward efficient distribution of the active component
over the treated surface. A surfactant is also essential for
obtaining a foam formulation. The surface-active substance to be
applied can comprise any physiologically and pharmaceutically
acceptable surfactant of combination thereof, including non-ionic,
anionic and amphoteric surface-active substances such as
alkyl-substituted polyglucose (n=1-3), anionic derivatives thereof
such as sodium cocopolyglucose tartrate, fatty acid esters of
lactic acid, lactylates, and polysorbates.
[0026] The invention also provides a packaging comprising a
composition according to any of the foregoing claims, and dosing
means adapted for oral administration of the composition. The
package is preferably also provided with dosing means. Depending on
the form of the composition (solid, liquid, gel, emulsion) this can
be for instance an atomizer, spray or gel dispenser.
[0027] It is advantageous if the dosing means comprise guide means
adapted to guide the. composition to the pharynx of a person for
treating. It is possible here to envisage a flexible hose with
which for instance a liquid can be deposited at the desired
location in the pharynx. The composition can in this way be used as
efficiently as possible.
[0028] Yet another preferred embodiment provides the measure that
the package comprises a container which comprises a propellant in
addition to the composition. Convenience of use is hereby greatly
enhanced.
[0029] Use can herein be made of a pressurized container wherein
the propellant is held in a flexible vessel in the container. This
is known as the so-called two-chamber system. The propellant does
not exit to the outside here, so there is a greater choice of
propellant. Propellant is understood to mean a gas under pressure.
This is preferably a pharmacologically acceptable gas or gas
mixture, such as compressed air, nitrogen or carbon dioxide.
[0030] According to yet another embodiment, the package is provided
with a valve adapted for placing between the lips. It is hereby
easy to reach the parts at the back of the pharynx to be contacted
with the composition, such as the uvula, by means of an aerosol
beam.
[0031] The same effect is also achieved when the package is
provided with a spout for guiding the composition to the
pharynx.
[0032] The invention further provides a method for manufacturing a
composition for treatment of snoring according to the invention,
comprising of mixing at least one active component with astringent
properties and a physiologically acceptable excipient. In addition,
other possible pharmaceutically acceptable additives as referred to
above can also be added so as to obtain the desired
composition.
[0033] The invention also provides for the use of marrubiin for the
manufacture of a medication for the treatment of snoring. Marrubiin
is found to have a particularly good anti-snoring effect. Marrubiin
is also understood to include the oxidation products marrubenol and
marrubiol directly obtainable from marrubiin, and other possible
synthetic and natural derived substances such as esterified
products. Marrubiin is present in 0.3-1.0% by weight in white
horehound and can be extracted therefrom as hydrophilic extract or
etheric oil. The extracts or oils of white horehound usually
comprise marrubiin as mixture with marrubenol and marrubiol. The
systematic name of marrubiin is
6-(2-furan-3-yl-ethyl)-6-hydroxy-2a,5a,7-trimethyldekahydronafto[1,8-bc]f-
uran-2-on. The chemical structure of marrubiin is shown below.
##STR00001##
The invention will now be elucidated with reference to the
following examples. The formulations A, B and C in table 1 are
found to have a good anti-snoring effect when applied in the
pharynx via the mouth. All formulations are based on water: the
shown percentages by weight are thus supplemented to 100% with
water. Composition A is a liquid composition which can be used for
applying with a spray or as droplets. Composition B is a gel
formulation. Composition C is a foam.
TABLE-US-00001 A B C white horehound 5 5 5 black horehound 5 5 5
thyme oil -- 0.1 0.1 ginger oil 0.15 -- 0.15 eucalyptus oil 0.05
0.1 0.05 peppermint oil 0.15 0.15 0.15 xylitol 3.6 3.6 5 betaine 3
3 3 oleth-20 0.8 0.6 1 pyridoxine HCl 0.5 0.6 0.7 dimethyl sulfone
3.5 5 3.5 hydroxypropyl -- 0.6 -- methylcellulose sodium cocopoly-
-- -- 0.8 glucose tartrate Water To 100% To 100% To 100%
The quantities of substances in table 1 are stated in percent by
weight. White horehound, black horehound, thyme, ginger, eucalyptus
and peppermint can be added as essential oil, extract or tincture.
The percentages by weight of thyme, ginger, eucalyptus and
peppermint in table 1 relate to the etheric oils. White horehound,
black horehound, ginger and thyme can be considered the most
important active components for the anti-snoring effect. Eucalyptus
oil, peppermint oil and MSM can be effectively deemed as substances
contributing toward the desired effect. Eucalyptus oil, peppermint
oil, xylitol also have a function as flavouring, wherein xylitol
also has a (limited) microbiological activity. Betaine is added as
osmosis regulator. Oleth-20 is a non-ionic surfactant which also
has a function as solubilizing agent for essential oils. Pyridoxine
is also known as vitamin B6 and helps to prevent mucous membrane
irritations and has expectorant (mucus-dissolving) properties. The
addition of a mucus-dissolving compound in an active quantity also
contributes toward the anti-snoring effect. Hydroxypropyl
methylcellulose is a gelling agent which also has bio-adhesive
properties. Sodium cocopolyglucose tartrate is a foaming agent and
is only present in the foam formulation C. All compositions are
supplemented to 100% with water. The compositions are obtained by
mixing the ingredients at suitable temperature and with suitable
techniques.
[0034] It will be apparent that many preferred variants of the
composition according to the invention can still be envisaged.
* * * * *