U.S. patent application number 15/312960 was filed with the patent office on 2017-07-06 for aqueous gel composition and its use.
The applicant listed for this patent is University of Copenhagen. Invention is credited to Daniel Bar-Shalom, Kasper Dalby, Jette Jacobsen, Anne Marie Lynge Pedersen, Peter Vilmann.
Application Number | 20170189333 15/312960 |
Document ID | / |
Family ID | 50774669 |
Filed Date | 2017-07-06 |
United States Patent
Application |
20170189333 |
Kind Code |
A1 |
Bar-Shalom; Daniel ; et
al. |
July 6, 2017 |
Aqueous gel composition and its use
Abstract
An aqueous gel composition comprising a) water, at least one
polysaccharide and at least one high molecular weight polyethylene
oxide, wherein the water content is at least 90% by weight of the
composition, and b) a local anaesthetic agent or an analgesic
agent, for use as a local anaesthetic or analgesic. The aqueous gel
shows transparency, lubricity, stringiness, elongation,
extensiveness, and cohesiveness while being devoid of taste and
smell and non-tacky or non-sticky.
Inventors: |
Bar-Shalom; Daniel;
(Kokkedal, DK) ; Jacobsen; Jette; (Olstykke,
DK) ; Dalby; Kasper; (Odense C, DK) ;
Pedersen; Anne Marie Lynge; (Charlottenlund, DK) ;
Vilmann; Peter; (Klampenborg, DK) |
|
Applicant: |
Name |
City |
State |
Country |
Type |
University of Copenhagen |
Copenhangen 01 |
|
DK |
|
|
Family ID: |
50774669 |
Appl. No.: |
15/312960 |
Filed: |
May 21, 2015 |
PCT Filed: |
May 21, 2015 |
PCT NO: |
PCT/EP2015/061282 |
371 Date: |
November 21, 2016 |
Current U.S.
Class: |
1/1 |
Current CPC
Class: |
A61K 9/0034 20130101;
A61K 9/06 20130101; A61K 47/10 20130101; A61K 31/47 20130101; A61K
31/245 20130101; A61K 31/439 20130101; A61K 45/06 20130101; A61K
9/006 20130101; A61K 47/38 20130101; A61K 31/167 20130101; A61K
31/445 20130101 |
International
Class: |
A61K 9/06 20060101
A61K009/06; A61K 47/10 20060101 A61K047/10; A61K 31/245 20060101
A61K031/245; A61K 45/06 20060101 A61K045/06; A61K 31/167 20060101
A61K031/167; A61K 31/445 20060101 A61K031/445; A61K 31/47 20060101
A61K031/47; A61K 47/38 20060101 A61K047/38; A61K 31/439 20060101
A61K031/439 |
Foreign Application Data
Date |
Code |
Application Number |
May 22, 2014 |
EP |
14169457.0 |
Claims
1. An aqueous gel composition comprising: a. water, at least one
polysaccharide and at least one high molecular weight polyethylene
oxide, wherein the water content is at least 90% by weight of the
composition; and b. a local anaesthetic agent or an analgesic
agent; for use as a local anaesthetic or analgesic for mucosal
membranes.
2. The aqueous gel composition according to claim 1, wherein the
water content is at least 95% by weight of the composition.
3. The aqueous gel composition according to claim 1, wherein the
water content is in the range 98-99.5% by weight of the
composition.
4. The aqueous gel composition according to claim 1, wherein the at
least one polysaccharide is selected from the group consisting of
cellulose and derivatives thereof, optionally substituted
alkylcelluloses, gums, pectin, carrageenan and alginates.
5. The aqueous gel composition according to claim 4, wherein the at
least one cellulose and derivatives thereof, optionally substituted
alkylcelluloses, gums, pectin and carrageenan is selected from the
group consisting of methylcellulose, carboxy-methylcellulose,
hydroxyethylcellulose, hydroxypropylcellulose,
hydroxypropylmethylcellulose, xanthan gum, tara gum, guar gum,
arabic (Acacia) gum, gellan gum, pullulan gum, cassia gum, carob
gum, carregeenan, pectin, locust bean gum, welan gum, konjac, and
karaya, preferably selected from the group consisting of
methylcellulose, carboxy-methylcellulose, hydroxypropyl
methylcellulose, xanthan gum, and guar gum, more preferably
methylcellulose, hydroxypropyl methylcellulose,
carboxymethylcellulose, gellan gum or xanthan gum.
6. The aqueous gel composition according to claim 4, wherein the at
least one cellulose and derivatives thereof is selected from
methylcellulose and hydroxypropyl methylcellulose, and is
preferably hydroxypropyl methylcellulose.
7. The aqueous gel composition according to claim 1, wherein the at
least one high molecular weight polyethylene oxide is of a
molecular weight 200,000 to 7,000,000 in the range.
8. The aqueous gel composition according to claim 1, wherein the
content of the at least one polysaccharide is in the range 0.1-3%
by weight of the composition.
9. The aqueous gel composition according to claim 1, wherein the
content of the at least one high molecular weight polyethylene
oxide is in the range 0.05-2% by weight of the composition.
10. The aqueous gel composition according to claim 1, wherein the
content of the at least one polysaccharide in the composition is in
the range 0.5-1.5% by weight of the composition, and the content of
the at least one high molecular weight polyethylene oxide in the
composition is in the range 0.1-1% by weight of the
composition.
11. The aqueous gel composition according to claim 1, wherein the
local anaesthetic agent or analgesic agent are selected from
procaine, amethocaine, cocaine, lidocaine (also known as
Lignocaine), prilocaine, bupivacaine, levobupivacaine, ropivacaine,
mepivacaine, dibucaine, benzocaine, tetracaine, etidiocine, and
ropivacaine.
12. The aqueous gel composition according to claim 1, further
comprising at least one additive selected from the group consisting
of a flavouring agent, a taste correcting substance, a colourant, a
pH regulating agent, a preservative, a texture modifier, a
therapeutically active agent, such as a caries-preventive agent, an
antifungal agent, an antibacterial agent, an antiviral agent, and
an anti-parasitic agent.
13. The aqueous gel composition according to claim 1, wherein the
aqueous gel composition is an oral or endoscopic local anaesthetic
or analgesic.
14. A saliva substitute composition comprising: a. water, at least
one polysaccharide and at least one high molecular weight
polyethylene oxide, wherein the water content is at least 90% by
weight of the composition; and b. optionally a caries-preventive
agent, an antifungal agent, an antibacterial agent, an antiviral
agent, an anti-parasitic agent, a flavouring agent, a taste
correcting substance, a texture modifier, a colourant, a pH
regulating agent, and a preservative.
15. A food lubricant comprising: a. water, at least one
polysaccharide and at least one high molecular weight polyethylene
oxide, wherein the water content is at least 90% by weight of the
composition; and b. optionally a caries-preventive agent, an
antifungal agent, an antibacterial agent, an antiviral agent, an
anti-parasitic agent, a flavouring agent, a taste correcting
substance, a texture modifier, a colourant, a pH regulating agent,
and a preservative.
16. An aqueous gel composition comprising water, at least one
polysaccharide and at least one high molecular weight polyethylene
oxide, wherein the water content is in the range 98-99.5% by weight
of the composition.
17. The composition according to any one of claims 14-16, wherein
the at least one polysaccharide is selected from the group
consisting of cellulose and derivatives thereof, optionally
substituted alkylcelluloses, gums, pectin, carrageenan and
alginates.
18. The composition according to any one of claims 14-16, wherein
the at least one high molecular weight polyethylene oxide is of a
molecular weight in the range 200,000-7,000,000.
19. The composition according to any one of claims 14-16, wherein
the content of the at least one polysaccharide in the composition
is in the range 0.5-1.5% by weight of the composition, and the
content of the at least one high molecular weight polyethylene
oxide in the composition is in the range 0.1-1% by weight of the
composition.
20. The composition according to any one of claims 14-16, further
comprising at least one additive selected from the group consisting
of a therapeutically active agent, such as a local anaesthetic
agent, an analgesic agent, an anti-infective agent such as an
antifungal agent, an antibacterial agent, an antiviral agent, and
an anti-parasitic agent, a caries-preventive agent, a flavouring
agent, a taste correcting substance, a texture modifier, a
colourant, a pH regulating agent, and a preservative.
21. An aqueous gel composition according to claim 16, wherein the
aqueous gel composition is a lubricant for mucosal membranes,
serosal surfaces and skin and for submucosal applications.
22. An aqueous gel composition according to claim 16, wherein the
aqueous gel composition is a lubricant for devices and
appliances.
23. The aqueous gel composition according to claim 3, wherein the
water content is in the range 98.5-99.5% by weight of the
composition.
24. The aqueous gel composition according to claim 3, wherein the
water content is in the range 98.7-99.3% by weight of the
composition.
Description
FIELD OF THE INVENTION
[0001] The present invention relates to an aqueous gel as well as
its use. More particularly the present invention relates to an
aqueous gel showing transparency, lubricity, stringiness,
elongation, extensiveness and cohesiveness while being devoid of
taste and smell and not being tacky. The aqueous gel according to
the invention may be used as a lubricant, e.g. as carrier for
active ingredients such as local anaesthetics, analgesics and other
API's and as a carrier for excipients, as a saliva replacement or
food lubricant, and as a lubricant on mucosal surfaces, serosal
surfaces and skin. Other uses may be submucosal application either
for endoscopic mucosal lifting or for carrier of excipients.
BACKGROUND OF THE INVENTION
[0002] Hydrophilic polymers are well known in the art as rheology
modifiers of aqueous systems. For instance, they are used as
thickeners for a wide range of functional systems such as
cosmetics, personal care products and medicine.
[0003] Local anaesthetics for use in the throat of a patient
undergoing direct oro-pharyngeal examination or surgery or
endoscopic examination of the upper gastrointestinal tract or
respiratory tract are known in the dosage forms of sprays or
viscous gels. However, the known products have a number of
drawbacks. Thus, those products are mostly disliked by patients as
they have an offending taste and numb, besides the intended site,
the tongue and parts of the buccal cavity. A spray, while usually
applied with a long nozzle directly to the throat, is transported
as aerosol by the breathing to the oral cavity. A gel, usually
applied with a spoon may spill on the way or regurgitate into the
mouth In the case of endoscopy procedures, the gel may interfere
with the clarity of the images.
[0004] Artificial saliva or saliva substitutes can be used to
replace moisture and lubricate in the oral cavity and thereby
alleviate oral dryness. These substitutes are available
commercially, but they can also be compounded. Artificial salivas
are formulated to mimic natural saliva. However, they are often
proven to be ineffective for most patients suffering from
persistent salivary gland hypofunction and xerostomia (i.e.,
sensation of dry mouth).
[0005] Saliva is important for the maintenance of oral health, and
also plays an essential role in a number of oral and
gastrointestinal functions. Consequently, patients with reduced
salivary secretion and changes in their saliva composition are more
susceptible to dental caries, oral infections and mucosal lesions,
and often have symptoms of a dry and sore mouth, burning and
itching oral mucosa, difficulties in chewing and swallowing dry
foods, impaired sense of taste, difficulty in speaking, and
problems with acid reflux. These distressing consequences of
salivary hypofunction also have a significant negative impact on
quality of life and general health status. Several diseases and
medical conditions as well as the medications used for treating
them, are associated with salivary gland hypofunction (objective
evidence of diminished salivary output) and xerostomia (subjective
sensation of dry mouth). In autoimmune diseases like Sjogren's
syndrome, salivary gland dysfunction is largely related to
structural changes in the salivary glands.
[0006] Patients who have undergone radiotherapy to cancer in the
head and neck region also often have reduced or no saliva
production due to destruction of the gland tissue.
[0007] Patients with salivary gland hypofunction often add sauces
and gravy to foods in large amounts to compensate for the lack of
saliva but in the case of salads and fruits which do not readily
form a bolus, this does not help, taste becomes a problem and
taking artificial saliva can be awkward and embarrassing (as well
as ineffective). Further, by changing the taste of the food item,
sauces and gravies make it harder to fully appreciate the original
taste. These problems with eating can lead to weight loss,
nutritional insufficiency, social isolation and impaired quality of
life.
[0008] Commercially available products come in a variety of
formulations including solutions, sprays, gels and lozenges. In
general, they contain an agent to increase viscosity, such as
carboxymethylcellulose or hydroxyethylcellulose, minerals such as
calcium and phosphate ions and fluoride, preservatives such as
methyl- or propylparaben, flavourings and related agents. Attempts
have been made to include "natural components" of saliva such as
hyaluronic acid or mucins but the results have been disappointing
and those products are expensive.
[0009] Different spray formulations are available, which are meant
to be applied directly to the mouth and throat of a patient
suffering from salivary gland hypofunction before swallowing a food
item. Alternatively (or alongside), the patient liquefies the food
in a blender or food processor.
[0010] The use of these formulations is associated with social
stigmatization, as it will be obvious for everyone that the patient
is struggling with the intake of food.
[0011] U.S. Pat. No. 4,740,365 discloses a sustained-release
preparation used for mucous membranes in the oral cavity.
[0012] U.S. Pat. No. 5,068,225 relates to a viscoelastic fluid for
use in surgery and other therapies and method of using same.
[0013] U.S. Pat. No. 6,133,325 relates to bioresorbable
compositions of carboxypolysaccharide polyether intermacromolecular
complexes and methods for their use in reducing surgical
adhesions.
[0014] U.S. Pat. No. 8,823,334 relates to a topical anesthetic
containing about 3 wt % to 10 wt % tetracaine in a vehicle suitable
for administration to the mucosa.
[0015] WO 92/03124 discloses a polymeric complex composition
comprising a reaction complex formed from a polycarbophil and
alginic acid.
[0016] WO 92/09256 relates to a water-based human tissue
lubricant.
[0017] WO 02/087519 relates to shaving compositions containing
highly lubricious water soluble polymers.
[0018] US 2005/0226822 relates to oral care products containing
ovomucin.
[0019] US2005/0244521 discloses a tobacco composition comprising
tobacco and a "format", wherein said composition is readily
disintegrable in the mouth, and wherein said format may comprise a
polymer.
[0020] WO 2006/028578 discloses use of polyethylene glycol based
fluidized polymer suspension in functional systems.
[0021] WO 2006/124219 discloses a shaving composition comprising
water, a water dispersible surface active agent, a lubricious water
soluble polymer, water insoluble particles, and a hydrogel-forming
polymer.
[0022] EP 0 613 684 relates to a solid form product for alleviating
xerostomia.
[0023] There is, however, a need for a lubricant for mucosal
membranes, serosal surfaces and for submucosal applications in the
form of a gel which exhibits stringiness and lubricity while not
being tacky.
OBJECT OF THE INVENTION
[0024] It is an object of embodiments of the invention to provide
an aqueous gel composition which acts as a lubricant for mucosal
membranes, serosal surfaces or skin, and which exhibits
stringiness, lubricity and is non-tacky.
[0025] It is a further object of embodiments of the invention to
provide a gel composition which fills as many functions of the
natural saliva as possible; it lubricates the mouth enabling normal
speech, provides a comfortable feeling of hydration, wetting and
lubrication, blends efficiently with solid food and lubricates the
passage of food through the throat.
[0026] It is a further object of embodiments of the invention to
provide a gel, which acts as a carrier for active ingredients to
the oral cavity and throat such as local anaesthetics, analgesics,
anti-inflammatory agents, anti-infective agents such as antifungal,
antibacterial, antiviral and anti-parasitic agents, caries
preventive agents, and optionally, pH regulating agents, flavouring
agents, taste correcting substances, texture modifiers, colourants
and preservatives.
[0027] It is a further object of embodiments of the invention to
provide a gel which is used to lubricate insertion of devices and
appliances to other body cavities such as vagina, uterus, rectum,
urethra, ear canal, lacrimal duct, nose, sinuses, thoracic and
abdominal cavity and oesophagus.
[0028] It is a further object of embodiments of the invention to
provide an aqueous gel composition which may be used to lift the
mucosa by submucosal injection either in order to perform
endoscopic submucosal resection/dissection or to function as a
carrier of active substances.
SUMMARY OF THE INVENTION
[0029] It has been found by the present inventors that, by
combining at least one polysaccharide and at least one high
molecular weight polyethylene oxide in a composition having a high
water content, an aqueous gel composition having a desirable
combination of properties is obtained.
[0030] So, in a first aspect the present invention relates to an
aqueous gel composition comprising: [0031] a) water, at least one
polysaccharide and at least one high molecular weight polyethylene
oxide, wherein the water content is at least 90% by weight of the
composition; and [0032] b) a local anaesthetic agent or an
analgesic agent;
[0033] for use as a local anaesthetic or analgesic.
[0034] In a second aspect the present invention relates to an
aqueous gel composition comprising:
[0035] a) water, at least one polysaccharide and at least one high
molecular weight polyethylene oxide, wherein the water content is
at least 90% by weight of the composition; and
[0036] b) optionally a caries-preventive agent, an antifungal
agent, an antibacterial agent, an antiviral agent, an
anti-parasitic agent, a flavouring agent, a taste correcting
substance, a texture modifier, a colourant, a pH regulating agent,
and a preservative;
[0037] for use as a saliva substitute.
[0038] In a third aspect the present invention relates to an
aqueous gel composition comprising:
[0039] a) water, at least one polysaccharide and at least one high
molecular weight polyethylene oxide, wherein the water content is
at least 90% by weight of the composition; and
[0040] b) optionally a caries-preventive agent, an antifungal
agent, an antibacterial agent, an antiviral agent, an
anti-parasitic agent, a flavouring agent, a taste correcting
substance, a texture modifier, a colourant, a pH regulating agent,
and a preservative;
[0041] for use as a food lubricant.
[0042] In a fourth aspect the present invention relates to an
aqueous gel composition comprising water, at least one
polysaccharide and at least one high molecular weight polyethylene
oxide, wherein the water content is above 98% by weight of the
composition, more preferably in the range 98.5-99.5% by weight of
the composition, such as in the range 98.7-99.3% by weight of the
composition.
[0043] In a fifth aspect the present invention relates to an
aqueous gel composition according to the invention for use as a
lubricant for mucosal membranes, serosal surfaces, skin and for
submucosal applications.
[0044] In a sixth aspect the present invention relates to an
aqueous gel composition according to the invention for use as a
lubricant for devices and appliances.
DETAILED DISCLOSURE OF THE INVENTION
Definitions
[0045] The term "aqueous gel" refers to an aqueous dispersion
comprising water and a hydrophilic polymeric substance dispersed
therein.
[0046] The term "additive" refers to any active ingredient for use
in an aqueous gel composition according to the invention.
Non-limiting examples thereof include local anaesthetics,
analgesics, anti-inflammatory agents, anti-infective agents such as
antifungal, antibacterial, antiviral and anti-parasitic drugs,
anti-caries agents or caries-preventive agents, and excipients such
as pH regulating agents, preservatives, texture modifiers,
colourants, flavouring agents and taste correcting substances.
[0047] The term "polysaccharide" refers to a polymeric carbohydrate
molecule composed of long chains of monosaccharide units bound
together by glycosidic linkages.
[0048] The term "cellulose" refers to an organic compound with the
general formula (C.sub.6H.sub.10O.sub.5).sub.n, a polysaccharide
consisting of a linear chain of several hundred to over ten
thousand .beta.(1->4) linked D-glucose units. A "derivative" of
cellulose refers to a cellulose compound, wherein the hydroxyl
groups thereof are partially or fully reacted with various
substituents.
[0049] The terms "polyethylene oxide" (PEO) and polyoxyethylene
(POE) refer to a polyether compound of the general formula
H--(O--CH.sub.2--CH.sub.2).sub.n--OH. Polyethylene glycol (PEG) has
the same structure as PEO/POE but the starting monomers ethylene
oxide and ethylene glycol respectively and the synthesis methods
used are different.
[0050] The term "saliva substitute" refers to a substance used to
substitute the saliva in patients having a dry mouth or
xerostomia.
[0051] The term "food lubricant" refers to a preparation which,
when added to food prior to insertion into the mouth will, upon
mastication enable the formation of an easily swallowable
bolus.
[0052] The terms "lubricancy" and "lubricity", which in the present
context are used interchangeably, refers to the property of a
composition to lubricate, i.e. make slippery, smooth and lessen
friction.
SPECIFIC EMBODIMENTS OF THE INVENTION
[0053] In an embodiment of the invention the water content of the
aqueous gel composition is at least 95% by weight of the
composition, more preferably at least 97% by weight of the
composition. Thereby a gel having highly desirable properties in
terms of stringiness, lubricity and cohesiveness may be
obtained.
[0054] In an embodiment of the invention the water content is above
98% by weight of the composition, more preferably in the range
98.5-99.5% by weight of the composition, such as in the range
98.7-99.3% by weight of the composition.
[0055] In an embodiment of the invention the at least one
polysaccharide is selected from the group consisting of cellulose
and derivatives thereof, optionally substituted alkylcelluloses,
gums, pectin, carrageenan and alginates.
[0056] In an embodiment of the invention the at least one cellulose
and derivatives thereof, optionally substituted alkylcelluloses,
gums, pectin and carrageenan is selected from the group consisting
of methylcellulose, carboxy-methylcellulose, hydroxyethylcellulose,
hydroxypropylcellulose, hydroxypropylmethylcellulose, xanthan gum,
tara gum, guar gum, arabic (Acacia) gum, gellan gum, pullulan gum,
cassia gum, carob gum, carregeenan, pectin, locust bean gum, welan
gum, konjac, and karaya.
[0057] In an embodiment of the invention the methylcellulose,
carboxy-methylcellulose, hydroxyethylcellulose,
hydroxypropylcellulose, hydroxypropylmethylcellulose, xanthan gum,
tara gum, guar gum, arabic (Acacia) gum, gellan gum, pullulan gum,
cassia gum, carob gum, carregeenan, pectin, locust bean gum, welan
gum, konjac, and karaya is preferably selected from the group
consisting of methylcellulose, carboxy-methylcellulose,
hydroxypropylmethylcellulose, xanthan gum, and guar gum, more
preferably methylcellulose, hydroxypropyl methylcellulose,
carboxymethylcellulose, gellan gum or xanthan gum. The above
polysaccharides are devoid of any taste and smell and are available
at low cost.
[0058] In an embodiment of the invention the at least one
polysaccharide is a methylcellulose or a hydroxypropylmethyl
cellulose and is preferably hydroxypropylmethyl cellulose (HPMC).
Methylcellulose and hydroxypropyl methylcellulose are available
commercially under the trade name METHOCEL.TM. as a line of
cellulose ether products produced by The Dow Chemical Company. The
initial letter identifies the type of cellulose ether. An "A"
identifies methylcellulose products and "E", "F", "K", "J" and
"310-series" identify different hydroxypropyl methylcelluloses.
[0059] In an embodiment of the invention the at least one high
molecular weight polyethylene oxide is of a molecular weight of at
least 200,000, preferably of a molecular weight of at least
600,000, preferably of a molecular weight of at least 1,000,000,
such as in the range 1,000,000 to 7,000,000, more preferably of a
molecular weight in the range 1,000,000-6,000,000, such as of a
molecular weight in the range 1,000,000 to 5,000,000, such as of a
molecular weight in the range 1,000,000 to 4,000,000. Polyethylene
oxide polymers are available commercially under the trade name of
POLYOX.TM. followed by a subscript indicating its type. Thus e.g.
POLYOX.TM. 301 refers to a PEO having a molecular weight of
approximately 4,000,000, whereas POLYOX.TM. 303 refers to a PEO
having a molecular weight of approximately 7,000,000.
[0060] In an embodiment of the invention the content of the at
least one polysaccharide is in the range 0.1-3% by weight of the
composition, more preferably in the range 0.3-2.0% by weight of the
composition, such as in the range 0.4-1.5% by weight of the
composition, more preferably in the range 0.5-1.5% by weight of the
composition, such as about 0.6-1.2% by weight of the composition,
such as about 0.8% by weight of the composition.
[0061] In an embodiment of the invention the content of the at
least one high molecular weight polyethylene oxide is in the range
0.05-2% by weight of the composition, more preferably in the range
0.1-1% by weight of the composition, more preferably in the range
0.1-0.5% by weight of the composition, such as about 0.3% by weight
of the composition.
[0062] In an embodiment of the invention the content of the at
least one polysaccharide in the composition is in the range
0.5-1.5% by weight of the composition, preferably in the range
0.6-1.2% by weight of the composition, such as about 0.8% by weight
of the composition, and the content of the at least one high
molecular weight polyethylene oxide in the composition is in the
range 0.1-1% by weight of the composition, preferably in the range
0.1-0.5% by weight of the composition, such as about 0.3% by weight
of the composition.
[0063] In an embodiment of the invention the aqueous gel
composition according to the invention comprises a local
anaesthetic agent or analgesic agent selected from procaine,
amethocaine, cocaine, lidocaine (also known as Lignocaine),
prilocaine, bupivacaine, levobupivacaine, ropivacaine, mepivacaine,
dibucaine, benzocaine, tetracaine, etidiocine, and ropivacaine. It
is to be understood, however, that the above list is non-exhaustive
and that other local anaesthetic agents or analgesic agents may be
used in a particular aqueous gel composition according to the
invention.
[0064] In an embodiment of the invention the aqueous gel
composition further comprises at least one additive. Non-limiting
examples thereof include additives selected from the group
consisting of a flavouring agent, a taste correcting substance, a
texture modifier (such as one or more lipids), a colourant, a pH
regulating agent, a preservative, a therapeutically active agent,
such as sucralfate, a steroid, a caries-preventive agent (such as
e.g. fluoride), an antifungal agent, an antibacterial agent (such
as e.g. Lyzozyme, triclosan, metronidazole), an antiviral agent
(acyclovir), and an anti-parasitic agent. A person skilled in the
art will readily be able to select any suitable additive according
to the purpose intended and it is to be understood, that the above
list is non-exhaustive and merely illustrate exemplary additives
and that other additives may be used singly or in combination in a
particular aqueous gel composition according to the invention.
[0065] The aqueous gel composition according to the invention may
be prepared in a manner known per se. Thus, non-limiting examples
of the preparation thereof may be found in Handbook of
Pharmaceutical Excipients, fifth ed., Raymond C Rowe et al. and
include mixing of the polymers with ice-cold water under vigorous
agitation; wetting the polymers with a portion of hot,
65-85.degree. C., water and then adding, under agitation, the rest
of the water as ice or ice-water; or the polymers may be moistened
with an organic solvent such as ethanol prior to the addition of
water.
[0066] In an embodiment of the invention the aqueous gel
composition comprises an active ingredient for the treatment of
oral mucosal conditions/diseases such as lichen planus,
candidiasis, angular cheilitis, recurrent aphthous stomatitis,
recurrent herpes labialis, glossitis/stomatitis migrans, discoid
lupus lesions, burning mouth syndrome, burning mouth syndrome,
mucositis a.o.
[0067] In another embodiment, it might be used as eye lubricant and
as carrier of active substances to the eyes.
[0068] Further, it may be used as lubricant in massage and sexual
activities.
[0069] In another embodiment, it might be used as a carrier of
active substances to the vagina, urethra, uterus, nose, sinus,
throat, ears, or rectum or any other mucosal or serosal tissue or
skin.
[0070] Finally it might be useful in lubricating skin to skin
friction, devices-skin friction, such as with prosthetic devices,
and friction of device parts such as endoscope against sleeves and
mouth-guards and intra-device friction such as wires in an
endoscope.
Example 1
[0071] A number of aqueous gel compositions were prepared by adding
the pre-weighted and premixed polymers to the water at low
temperature (under 3.degree. C.) while agitating the water with an
Electrolux Stick Mixer ES.TM. 6200 at highest speed. The agitation
was maintained until no more dry particles or lumps could be
seen.
[0072] The quality of the individual gel compositions appears from
the below table I.
TABLE-US-00001 TABLE I Material 1 Material 2 (M1) (M2) Molecular
structure material 1 Methocel K250M (HPMC) Polyox 301 ##STR00001##
Methocel K250M (HPMC) -- ##STR00002## Polyox 301 -- ##STR00003##
Methocel K250M (HPMC) Polyox N60K ##STR00004## Methocel K250M
(HPMC) Polyox N12K ##STR00005## Maize starch -- ##STR00006## Maize
starch Polyox 301 ##STR00007## CMC 40.000 Polyox 301 ##STR00008##
Kelcogel (gellan gum) Polyox 301 ##STR00009## Methocel K15M (HPMC)
Polyox 301 ##STR00010## Keltrol (xanthan gum) Polyox301
##STR00011## Methyl- cellulose SGA -- ##STR00012## Methyl-
cellulose SGA Polyox 301 ##STR00013## Methocel A40M (MC) Polyox 301
##STR00014## Methocel fast hydrating K100M (HPMC) Polyox 301
##STR00015## Methocel K4M (HPMC) Polyox 301 ##STR00016## Methocel
K4M (HPMC) -- ##STR00017## Methocel F4M (HPMC) Polyox 301
##STR00018## Methocel F4M (HPMC) -- ##STR00019## Methocel E4M
(HPMC) Polyox 301 ##STR00020## Methocel E4M (HPMC) -- ##STR00021##
Methocel A4M (MC) Polyox 301 ##STR00022## Methocel A4M (MC) --
##STR00023## Arabic gum -- Arabic gum Polyox 301 Material 1
Molecular structure Quality Conc. (M1) material 2 of gel Comment
(M1%, M2%) Methocel K250M (HPMC) ##STR00024## - + ++ +++ +++
0,03/0,3 0,1/0,3 0,3/0,3 0,8/0,3 1,0/0,3 Methocel K250M (HPMC) -- +
++ ++ No stringiness (all conc.) 0.6 0.8 1.0 Polyox 301 -- -- Water
like with stringiness 0.3 Methocel K250M (HPMC) ##STR00025## ++
Thin 0,8/1,5 Methocel K250M (HPMC) ##STR00026## ++ Thin 0,8/0,75
Maize starch - Jelly 10 Maize starch ##STR00027## + Jelly/gel 5/0,3
CMC 40.000 ##STR00028## +++ 0,8/0,3 Kelcogel (gellan gum)
##STR00029## ++ ++ - Jelly 0,1/0.3 0,2/0,3 0,8/0,3 Methocel K15M
(HPMC) ##STR00030## ++ 0,8/0,3 Keltrol (xanthan gum) ##STR00031## -
Jelly 0,7/0,3 Methyl- cellulose SGA -- - + Very thin 2 5 Methyl-
cellulose SGA ##STR00032## +(+) 5/0,3 Methocel A40M (MC)
##STR00033## + A thin gel 0,8/0,3 Methocel fast hydrating K100M
(HPMC) ##STR00034## ++ 0,8/0,3 Methocel K4M (HPMC) ##STR00035## +
0,8/0,3 Methocel K4M (HPMC) -- - 0,8 Methocel F4M (HPMC)
##STR00036## - 0,8/0,3 Methocel F4M (HPMC) -- - 0,8 Methocel E4M
(HPMC) ##STR00037## + 0,8/0,3 Methocel E4M (HPMC) -- - 0,8 Methocel
A4M (MC) ##STR00038## + 0,8/0,3 Methocel A4M (MC) -- 0,8 Arabic gum
+(+) - Arabic gum ##STR00039## ++ -
Example 2
[0073] An aqueous vehicle having the following composition:
[0074] 0.2% by weight of polyethylene oxide (Polyox WSR 301)
[0075] 0.5% by weight of HPMC (Methocel K250M)
[0076] q.s. water
[0077] was prepared by adding the polyethylene oxide and HPMC to
ice-cold water while agitating the mixture with an Electrolux Stick
Mixer ES.TM. 6200 at highest speed. The agitation was maintained
until no more dry particles or lumps could be seen. Sucralfate in
an amount of 5.3% by weight of the above vehicle was added under
stirring to obtain a sucralfate-containing gel composition.
[0078] The sucralfate-containing gel composition was administered
to patients with xerostomia also having inflammatory mucosal
lesions twice daily at a dose of one spoonful per dose. Significant
symptom relief was observed after a few days of treatment.
LIST OF REFERENCES
[0079] U.S. Pat. No. 4,740,365 [0080] U.S. Pat. No. 5,068,225
[0081] U.S. Pat. No. 6,133,325 [0082] U.S. Pat. No. 8,623,334
[0083] WO 92/03124 [0084] WO 92/09256 [0085] WO 02/087519 [0086] US
2005/0226822 [0087] US 2005/0244521 [0088] WO 2006/028578 [0089] WO
2006/124219 [0090] EP 0 613 684
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