U.S. patent application number 17/091733 was filed with the patent office on 2021-04-29 for surface sterilisation by misting with a bioflavanoid solution.
The applicant listed for this patent is CITROX BIOSCIENCES LIMITED. Invention is credited to Ian Ripley, Howard Thomas.
Application Number | 20210120816 17/091733 |
Document ID | / |
Family ID | 1000005329102 |
Filed Date | 2021-04-29 |
United States Patent
Application |
20210120816 |
Kind Code |
A1 |
Thomas; Howard ; et
al. |
April 29, 2021 |
SURFACE STERILISATION BY MISTING WITH A BIOFLAVANOID SOLUTION
Abstract
There is described a method of sterilizing surfaces using
flavanoids, for example mixtures containing inter alia naringin and
neohesperidin, by misting.
Inventors: |
Thomas; Howard; (Cambridge,
GB) ; Ripley; Ian; (Middlesbrough, GB) |
|
Applicant: |
Name |
City |
State |
Country |
Type |
CITROX BIOSCIENCES LIMITED |
Cambridgeshire |
MA |
US |
|
|
Family ID: |
1000005329102 |
Appl. No.: |
17/091733 |
Filed: |
November 6, 2020 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
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15916465 |
Mar 9, 2018 |
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17091733 |
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13147949 |
Aug 4, 2011 |
9913470 |
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PCT/GB2010/050180 |
Feb 4, 2010 |
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15916465 |
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Current U.S.
Class: |
1/1 |
Current CPC
Class: |
A01N 65/08 20130101;
A01N 43/26 20130101; A01N 65/36 20130101; A23L 3/3562 20130101;
A23L 3/3499 20130101; A23L 3/3472 20130101; A01N 43/32 20130101;
A23L 3/3544 20130101; A01N 43/16 20130101 |
International
Class: |
A01N 43/16 20060101
A01N043/16; A23L 3/3472 20060101 A23L003/3472; A01N 43/32 20060101
A01N043/32; A01N 43/26 20060101 A01N043/26; A23L 3/3544 20060101
A23L003/3544; A23L 3/3562 20060101 A23L003/3562; A23L 3/3499
20060101 A23L003/3499; A01N 65/08 20060101 A01N065/08; A01N 65/36
20060101 A01N065/36 |
Foreign Application Data
Date |
Code |
Application Number |
Feb 5, 2009 |
GB |
0901901.9 |
Claims
1-25. (canceled)
26. A method of sterilising a surface comprising misting the
surface with a naringin solution optionally wherein the surface is
within a hospital, ambulance, home, mortuary, gym, changing room,
school, public transport, or nursing home.
27. The method of claim 26, wherein the naringin solution comprises
50-65% by weight of a mixture of bioflavonoids wherein the mixture
of bioflavonoids comprises at least 25% by weight neohesperidin
optionally wherein the mixture of bioflavonoids comprises
HPLC-45.
28. The method of claim 27, wherein the misting of the naringin
solution results in a mist in the form of droplets ranging between
0.5-5.mu. in size.
29. The method of claim 27, wherein the narigin solution comprises
0.5-7.5% by weight of the mixture of bioflavonoids.
30. The method of claim 29, wherein the narigin solution comprises
a pharmaceutically acceptable salt of chlorine.
31. The method of claim 29, wherein the narigin solution further
comprises a non-ionic surfactant.
32. The method of claim 31, wherein the narigin solution further
comprises a thickening agent.
33. The method of claim 32, wherein the thickening agent is a
polysaccharide thickening agent.
34. The method of claim 26, wherein the misting comprises
dispersing a mist from a misting device.
35. The method of claim 34, wherein the misting device is a
hand-held misting device or a wall mounted mister.
36. The method of claim 34, wherein the misting device is a dry
misting device.
37. The method of claim 26, wherein the misting comprises
dispersing a mist from a wall mounted mister or a hand-held misting
device for sterilising in a domestic situation.
38. A method of reducing bacterial count or external parasites on a
person or their clothing, which comprises misting said person or
clothing with a mist of a naringin solution.
39. The method of claim 38, wherein the naringin solution comprises
a mixture of bioflavonoids wherein the mixture of bioflavonoids
comprises 50-65% by weight naringin and at least 25% by weight
neohesperidin.
40. The method of claim 39, wherein the mist comprises droplets of
ranging between 0.5-5.mu. in size.
41. The method of claim 40, wherein the narigin solution further
comprises a non-ionic surfactant and a polysaccharide thickening
agent.
42. The method of claim 39, wherein the mixture of bioflavonoids
comprises HPLC-45.
43. The method of claim 26 wherein the surface is within an
ambulance, which can be occupied or reoccupied promptly after
misting the surface.
Description
RELATED APPLICATIONS
[0001] This application is a continuation of U.S. patent
application Ser. No. 15/916,465, filed Mar. 9, 2018, which is a
continuation of U.S. patent application Ser. No. 13/147,949, filed
Aug. 4, 2011, now U.S. Pat. No. 9,913,470, which is a 35 U.S.C.
.sctn. 371 filing of International Patent Application No.
PCT/GB2010/050180, filed Feb. 4, 2010, which claims priority to
United Kingdom Patent Application No. 0901901.9, filed Feb. 5,
2009, the entire disclosures of which are hereby incorporated
herein by reference.
[0002] The present application relates to the sterilisation of
surfaces by misting. More specifically this present application
relates to the use of compositions containing certain flavonoids
for sterilisation of surfaces, including those present in
hospitals, ambulances and kitchens, by misting.
[0003] Applications numbers PCT/GB2007/002756 and
PCT/GB2007/002758, disclose compositions comprising certain
flavonoids for use in oral and topical applications. It has now
been found that surfaces may be sterilised by misting using
compositions which contain some or similar flavonoids.
[0004] Accordingly the present invention provides a method of
sterilising surfaces by misting which employs a compound of the
Formula (I):
##STR00001##
wherein wherein R.sup.1 is hydroxyl or methoxyl and R.sup.2 is
hydrogen, hydroxyl or methoxyl and X is hydrogen or a
saccharide.
[0005] Aptly R.sup.2 is hydrogen and R.sup.1 is in the 3- or
4-position. Alternatively, aptly R.sup.2 is 3-hydroxy and R.sup.1
is 4-methoxyl.
[0006] Suitably X in a compound of the Formula (I) is H.
[0007] Suitably X in a compound of Formula (I) is a saccharide.
[0008] Favourably X is a disaccharide.
[0009] Suitable disaccharides include combinations of two
monosaccharide, suitably pyranoses, linked by a glycosidic bond,
for example rhamnose and glucose, for example L-rhamnose and
D-glucose.
[0010] Suitable disaccharides can have the structure:
##STR00002##
wherein one of R.sup.3 and R.sup.4 is H and the other OH or both
are H or both are OH. Aptly R.sup.3 is H and R.sup.4 is OH so that
the disaccharide is rutinose.
[0011] Favoured aglycones of flavonoids for use in this invention
are the disaccharides
6-O-(alpha-L-rhamnopyranosyl)-beta-D-glucopyranose, also known as
rutinose, and
2-O-(alpha-L-rhamnopyra-nosyl)-beta-D-glucopyra-rose.
[0012] It is presently believed that the flavonoids very suitably
comprise naringin or neohesperidin or mixtures thereof. Mixtures of
one or both of naringin and neohesperidin with for example, one,
two or three other flavanoids of the Formula I are presently
believed particularly favoured for use in this invention. Such
mixtures can be obtained from extraction from bitter oranges.
[0013] Suitable compounds of Formula (I) include Neoeriocitrin,
Isonaringin, Naringin, Hesperidin, Neohesperidin, Neodiosmin,
Naringenin, Poncirin and Rhiofolin.
[0014] Favoured compositions for use include those which comprise
either of naringin and neohespiridin or both.
[0015] Particularly aptly the invention will contain naringin and
neohesperidin and other flavonoids of the Formula (I).
[0016] The mixture of flavonoids may aptly contain more than one of
neohesperidin, naringin, isocriocrin, isonaringin, naringin,
hesperidine, neohesperidin, neocliomin, naringenin, poncrin and
rhiofolin. Such a mixture of flavonoids can be obtained from bitter
oranges, see for example PCT/GB2007/002756. Suitable mixtures can
include 2, 3, 4, 5, 6, 7, 8, 9 or more compounds of Formula (I).
Thus a mixture comprising 2, 3, 5, 6, 7, 8 or 9 of the above named
flavonoids is apt, for example containing 3, or containing 4, or
containing 5, or containing 6, or containing 7, or containing 8 or
containing 9 of said flavonoids.
[0017] It is presently believed that mixtures of such flavonoids
have advantages over the use of a single flavonoid. It is
particularly advantageous that extract of bitter oranges may be
employed without the need for isolating individual flavonoids if
desired. The use of the composition generally comprising biomass
enhances solubility of the flavanoids. Generally the flavanoids are
present in mixtures with biomass by about 10% to 75%, more aptly
30% to 60%, for example 40% to 50%, preferably about 45%. The
biomass comprises pectins and other sugar derived materials.
Typically about 40% of low molecular weight pectins are
present.
[0018] If it is desired to avoid biomass, other solubilising agents
such as dextrins, for example cyclodextrin, may be employed if
desired.
[0019] Aptly the mixture of flavonoids will comprise at least 25%,
more suitably at least 40% and preferably at least 50% of naringin.
More aptly the mixture will contain up to 65% of naringin.
[0020] Aptly the mixture of flavonoids will comprise at least 15%,
more suitably at least 20% and preferably at least 25% of
neohesperidin. More aptly the mixture will contain up to 35% of
neohesperidin.
[0021] In a favoured form the mixture will contain at least 75% of
neohesperidin and naringin.
[0022] A particular advantage of many compositions of the invention
is that they may employ compounds of natural origin. Thus, for
example, it is preferred to employ compounds of the Formula
(I).
[0023] The use of these compositions does not require long periods
where noxious gases can dissipate before the area can be utilized
again. Similarly the sterilised area does not possess an
appeasement order for long periods after sterilisation.
[0024] Compositions of the invention may be adapted for application
to external surfaces including external surfaces of plants or
animals. Often the animal is a human. Human clothing may also be
misted to reduce the burden of unwanted organisms.
[0025] The compositions of the flavonoids show activity against a
wide range of organisms including gram positive bacteria, gram
negative bacteria, fungi, virus, protazoans and insect parasites
when misted. Particularly surprising the misting may be employed
against difficult bacteria such as methicillin resistant
Staphylococcus aureus (MRSA), Clostridium difficile (C. diff)
Helicobacter pyroli (H. py), and vancomycin resistant
enterobacteria.
[0026] The compositions may be used to mist animals. Suitable
animals include humans and food and companion animals such as cows,
pigs, horses, chickens, sheep, goats, dogs and cats.
[0027] Suitable compositions for misting include those analogous to
those described in PCT/GB2007/002756 and PCT/GB2007/002758.
[0028] These compositions may be in the form of solutions, dusting
powders and other aerially dispersible powder and liquids and the
like. Liquid forms are presently preferred. The use of "dry" mists
of aqueous solutions can also be favourable.
[0029] UK Patent Application No 2450536 discloses misting devices
that may be employed to mist solutions of the flavanoids described
herein. This can be in the form of droplets of 0.5 to 5.mu., for
example about 1.mu.. These give the dry feel to the dispersion.
Solutions of 0.5 to 7.5%, more aptly 1 to 5%, for example 1, 2, 3,
4 or 5% of HPLC-45 (see Example 1), or other flavanoid compositions
described herein may be employed for dispersal.
[0030] Such compositions may be used to reduce the bacterial count
on body surfaces, clothing and in the general environment
particularly in hospitals, ambulances, nursing homes especially for
the elderly or the like where it is particularly desirable to
reduce the presence of bacteria such as MRSA, C. difficile or the
like.
[0031] The compositions may be similarly employed in the home, for
example in the kitchen, bathroom or toilet.
[0032] Small wall mounted misters may be employed in the domestic
situation and also in hospital rooms and wards.
[0033] Such compositions may also be employed to mist equipment
such as stethoscopes and other medical equipment.
[0034] A particular use of the composition is to mist hospital and
other mattresses. This may play a role in reducing the transmission
of Staphylococcus including MSRA.
[0035] The substantivity of the compositions following misting (as
opposed to rapid diminution of effectiveness of ethanol) is an
advantage.
[0036] If external surfaces of enclosed spaces, such as ambulances,
operating theatres, wards, kitchens (and even mortuaries) and so on
are to be treated, it is particularly suitable to do so by
"misting". In this a fine aerial dispersion of powder or
microdroplets of composition are dispersed within the enclosed
space. This can then offer a non-toxic alternative to the presently
employed methods which often employ noxious gases. Since the
compositions of the invention have such low toxicity they may be
employed on patients and their visitors and associated clothing,
linen and the like by "misting". Such "misting" is of use in
vehicles such as ambulances which are required to be free of
pathogens or at least have them reduced to an acceptable level, but
likewise free of residual odors that are typically left following
the use of noxious gases. This equally applies to other areas
requiring treatment. Compositions used in this way may be in the
form of a dispersible liquid, for example akin to the soap or
shampoo or skin foaming compositions described hereinafter.
[0037] Thus it is possible by misting compositions of this
invention to treat hands, the face and skin generally and the hair,
both on the head and elsewhere. This can be employed to reduce
bacterial count and so help to reduce the spread of methicillin
resistant Staphylococcus aureas, Clostridium difficile and other
bacteria. Similarly, misting clothing, hospital bedding and
mattresses and the like can have a similar beneficial result. A
further benefit is that such compositions may be used to reduce
viral transmission, for example for influenza virus, which can
occur by hand contamination. Other virus that may be on the skin or
membranes include HIV, herpes and the like which are also minimized
by use of the compositions of the invention adapted for
administration to the skin or membranes. The use of this invention
in treating environments which may contain multiple resistant
vancomysin enterococci or spore forming organisms such as
Clostridium difficile may be advantageous.
[0038] External Parasite infestation may be treated by misting with
compositions of the invention. External parasites that may be
treated by misting include lice, especially head lice, and scabies
and fleas.
[0039] Compositions of the invention may therefore also suitably
contain a pharmaceutically acceptable salt of choline such as
choline chloride. This can enhance effectiveness further against
organisms such as C. difficile.
[0040] Formulations may be composed of conventional carriers as
long as they are compatible with the active components of the
compositions herein.
[0041] The mistable composition may aptly contain surfactants. Many
conventional surfactants may be employed but it appears certain
effective formulations will employ non-ionic surfactants.
Particularly effective non-ionic surfactants include alkyl
polycyclosides and/or alkenyl polyglycosides (APG's) such as those
containing up to 10 sugar residues coupled to a hydrocarbon chain.
Oligomerisation of up to about 4 sugar residues can be desirable.
Such surfactants are available under the trade name "Plantacare"
for example from Henkel as "Plantacare 2000".
[0042] In some compositions minor amounts of typical anionic
surfactants may be employed together with the non-ionic surfactant.
Amphoteric surfactants may also be present with the non-ionic
surfactants, for example those having secondary or tertiary amino
and water solubilising anionic groups, such as sulphate, phosphate,
phosphonate or carboxylate groups. Such amphoteric surfactants
include those available under trade names such as Miranol (of
Rhone-Poulenc) and Betain, such as Dehyton from Henkel.
[0043] The compositions of the invention may optionally comprise
thickening agents. Suitable thickening agents include
polysaccharide thickeners such as xanthan gums, gellan gums,
pectins, carageenans and the like. An apt thickening agent is
xanthan gum such as Keltrol CG which is a high molecular weight
polysaccharide produced by microbial fermentation. Viscosity may
also be selected by use of an amphoteric surfactant such as a
cocamido-propyl betain or Tego Betain F50 as a thickening as well
as surfactant agent.
[0044] Misting may be performed in gyms, changing rooms, schools,
public transport and other areas where it is particularly
advantageous to employ non-noxious sterilizing systems.
[0045] The use in such areas can have the added benefit of
deodorizing the areas.
[0046] The compositions of the invention may be misted for the
treatment of food stuffs to reduce or eliminate unwanted pathogens
or organisms leading to reduction in storage life of food stuffs.
Thus vegetable, fruits and meat may be treated, for example
lettuce, tomatoes, cucumbers, peppers, cereals such as wheat and
maize, fruit such as apples, grapes, pears and figs, and meats such
as beef, pork, lamb, bacon and the like.
[0047] The skilled person understands that "sterilizing" in the
context of this document may have the normally recognized meaning
to the skilled person of reducing or eliminating unwanted pathogens
or organisms in the relevant environment to a level where the
environment is then more fit for purpose, for example not
presenting a health risk.
EXAMPLE 1
[0048] Water was added to a beaker and stirring commenced. Keltrol
CG-SFT (9.0 g; 1.8%) was added and stirring continued until
dissolved. Citrox HXT powder (2.5 g; 0.5%) was added and stirring
continued until dissolved. Glycerol (5.0 g; 1.0%) was added and
stirring continued until dissolved. (The water was sufficient to
make up to 100%).
[0049] The resulting viscous gel was de-aerated. The pH was 4-5.
The viscosity 7000-10000 cp at 20.degree. C. (spindle 4/0 rpm). The
pH may be adjusted with citric acid if required to bring it within
the stated range.
[0050] Citrox HXT powder comprises on a wt/wt basis 7.5% HPLC 45%,
citric acid 30%, willow bark extract 50% and Olea Europeae extract
12.5%.
[0051] HPLC-45% contained 45% by weight of a mixed of flavanoids
together with residues of extraction from bitter oranges.
[0052] The mixture of flavanoids in HPLC-45 comprises:
TABLE-US-00001 % in HPLC 45 (bioflavonoid Bioflavonoid component +
biomass) Neoeriocitrin 1.1 Isonaringin 1.2 Naringin 23.4 Hesperidin
1.4 Neohesperidin 12.5 Neodiosmin 1.4 Naringenin 1.5 Poncirin 2.0
Other 0.5 (Rhiofolin) Total 45% of HPLC 45
EXAMPLE 2
[0053] Water was added to a beaker and stirring commenced. Keltrol
CG-SFT (9 g, 1.8%), Plantacare 2000 (67.8 g, 13.6%), Tego Betain
F50 (10 g, 2%), glycerol (10 g, 2%) and Citrox HXT powder were
sequentially added with stirring until complete dissolution
occurred prior to adding subsequent ingredients. (The water was
sufficient to make up to 100%).
[0054] The product was a clear viscous gel, pH 4.8 to 5 was a
viscosity of about 4000 cp at 20.degree. C. (spindle 4/10 rpm).
[0055] Citrox HXT powder and Keltrol CG-SFT were as described in
Example 1.
[0056] Plantacare 2000 is an aqueous solution containing 6.78 g of
C.sub.8-C.sub.16 fatty alcohol polyglycoside.
[0057] Tego Betain F50 is an aqueous solution containing 3.22 g of
cocamidopropyl betaine.
EXAMPLE 3
[0058] This was prepared by mixing as described in Example 1.
TABLE-US-00002 Salicylic acid 0.25% Citric acid 0.15% HPLC 45%
0.0375% Betafin BP20 1.0% Glycerine 0.5% Dermosoft GMCY 1.0% Water
97.0%
EXAMPLE 4
[0059] This was prepared by mixing as described in Example 1.
TABLE-US-00003 Keltrol CG-SFT 1.7% HPLC 45% 0.0375% Citric acid
0.15% Salicylic acid 0.25% Dermosoft GMCY 1.0% Glycerine 1.0% Water
95.8%
EXAMPLE 5
TABLE-US-00004 [0060] Keltrol CG-SFT 1.8% Plantacare 2000 13.56%
Tego Betain F50 9.48% Glycerine 1.0% HPLC 45% 0.0375% Citric acid
0.15% Salicylic acid 0.25% Dermosoft GMCY 1.0% Water 72.66%
[0061] When used herein HPLC 45% means a mixture containing 45% of
bioflavanoids and 55% of other matter from extraction of bitter
oranges. The bioflavanoids comprised naringin (about 52%),
neohesperidin 28%, poncirin (4%), naringenin (3%), hesperidin (3%),
neodiosmin (3%), isonaringin (3%), isocriocrin (2%), other minor to
100%.
EXAMPLE 6
[0062] Example 5 is repeated by adding choline chloride (1.25 g;
0.25%) after the keltrol and stirring until dissolved.
EXAMPLE 7
[0063] Compositions formulated as exemplified in PCT/GB2007/002756
and PCT/GB2007/002758 are misted from a misting device.
EXAMPLE 8
[0064] Compositions 1 to 6 are misted from a misting device.
[0065] A commercial hand held misting device is used to direct mist
at the surfaces in an ambulance and to the air space. The misting
is continued until the operative is satisfied surfaces have been
thoroughly treated.
[0066] The ambulance may be occupied twenty minutes after the
completion of the misting.
EXAMPLE 9
[0067] A composition described in Example 1 was used to mist a
microbiological research laboratory to reduce biological
contamination. The misting was performed for three hours. If entry
to the laboratory had become necessary, this would have been
possible owing to the lack of significant toxicity of the mist. A
conventional commercial misting device was employed.
[0068] The Nebulair was turned on each night for three hours in a
sealed room over a 16 day period. A 1% aqueous solution of HPLC-45
as described in Example 1 was used between day 1 and 7 and was then
increased to a 2% aqueous solution. An area of 100 cm.sup.2 was
swabbed using a saturated swab and added to a sterile tube
containing 3 ml maximum recovery diluent (MRD). The tubes were
vortexed for 20 seconds and then left to stand for 20 minutes. The
swabs were removed and 100 .mu.l (Day 0 and Day 1) or 200 .mu.l
(Day 3, 9, 11, and 16) of MRD was spread on TSB agar plates. A
clean swap was used as a control. The plates were incubated at
37.degree. C. for 24 hours and the average number of colonies per
plate was recorded.
[0069] Results:
TABLE-US-00005 Colony Forming Units (CFU) per 100 cm.sup.2 Day Day
Day Day Day Day 0 1 3 9 11 16 Computer 3600 435 195 285 97.5 90
Desk 1 600 45 15 15 7.5 0 Desk 2 60 0 15 7.5 15 7.5 Desk 3 150 45
75 7.5 7.5 0 Desk 4 150 15 15 7.5 7.5 0 Under Desk 150 15 30 0 0 0
Bin 510 240 45 22.5 22.5 15 Sink 1890 570 172.5 82.5 210 127.5
Centrifuge 210 45 90 37.5 15 0 Extractor fan 255 225 15 45 15 15
Water Bath 660 90 30 22.5 22.5 7.5 Note: Bioflavanoid mixture
concentration increased from 1% to 2% after day 7 Day 0 indicates
contamination levels before misting treatment
EXAMPLE 10
[0070] The surface of a hospital mattress was misted with either 3%
or 5% aqueous solutions of HPLC-45 (see Example 1) for 3 hours from
a commercial dry misting nebulisor (Nebulair). The misting in both
cases was effective in reducing the presence of multiple resistant
Staphylococcus aurous to a greater extent than was achieved by the
hospitals conventional treatment.
* * * * *