U.S. patent application number 13/989560 was filed with the patent office on 2013-11-21 for composition i - i and products and uses thereof.
This patent application is currently assigned to SMITH & NEPHEW PLC. The applicant listed for this patent is Marcus Damian Phillips. Invention is credited to Marcus Damian Phillips.
Application Number | 20130310780 13/989560 |
Document ID | / |
Family ID | 43500630 |
Filed Date | 2013-11-21 |
United States Patent
Application |
20130310780 |
Kind Code |
A1 |
Phillips; Marcus Damian |
November 21, 2013 |
COMPOSITION I - I AND PRODUCTS AND USES THEREOF
Abstract
A curable composition apportioned between at least one Part A
and at least one Part B, the Parts sealed within barrier means in
manner to prevent contamination thereof, the composition
comprising: (i) one or more alkenyl-containing prepolymers having
at least one alkenyl moiety per molecule, ii) one or more
SiH-containing prepolymers having at least one SiH unit per
molecule, and additionally: (iii) a catalyst for curing by addition
of alkenyl-containing prepolymer (i) to SiH-containing prepolymer
(ii), wherein the at least one Part A and at least one Part B are
provided within or upon at least two respective receptacles or
supports and are adapted to be dispensed or released therefrom in
cooperative manner facilitating intimate contact and curing
thereof, wherein the receptacle(s) or support(s) for at least one
of Part A and Part B is thermally stable at elevated temperature of
123 C for a period in excess of 18 hours, methods for preparing the
composition, methods for sterilisation thereof, medical and
non-medical use thereof, a device incorporating the composition,
and a precursor therefor including its sterilisable precursor
composition, in particular a terminally sterilisable or terminally
sterile composition for medical use, particularly in wound therapy,
more particularly as a wound packing material which can be shaped
and configured to the shape of a wound, most particularly for
application in negative pressure wound therapy (NPWT).
Inventors: |
Phillips; Marcus Damian;
(Heslington, GB) |
|
Applicant: |
Name |
City |
State |
Country |
Type |
Phillips; Marcus Damian |
Heslington |
|
GB |
|
|
Assignee: |
SMITH & NEPHEW PLC
London
GB
|
Family ID: |
43500630 |
Appl. No.: |
13/989560 |
Filed: |
November 25, 2011 |
PCT Filed: |
November 25, 2011 |
PCT NO: |
PCT/GB11/01649 |
371 Date: |
August 8, 2013 |
Current U.S.
Class: |
604/319 ;
366/177.1; 521/134; 525/100 |
Current CPC
Class: |
A61L 26/0095 20130101;
A61L 15/58 20130101; A61L 24/0073 20130101; C08L 83/04 20130101;
A61P 17/00 20180101; A61P 1/02 20180101; A61L 15/26 20130101; A61P
17/02 20180101; A61L 15/26 20130101; A61L 15/58 20130101; A61L
15/425 20130101; C08L 83/04 20130101 |
Class at
Publication: |
604/319 ;
521/134; 525/100; 366/177.1 |
International
Class: |
A61L 15/42 20060101
A61L015/42; A61L 24/00 20060101 A61L024/00; A61M 1/00 20060101
A61M001/00; A61L 26/00 20060101 A61L026/00 |
Foreign Application Data
Date |
Code |
Application Number |
Nov 25, 2010 |
GB |
1020005.3 |
Claims
1. A curable composition, apportioned between at least one Part A
and at least one Part B, the composition comprising: one or more
alkenyl-containing polymers having at least one, or at least two,
alkenyl moiety per molecule, one or more SiH-containing polymers
having at least one, or at least two, SiH unit per molecule, a
catalyst for curing by addition of an alkenyl-containing polymer to
a SiH-containing polymer (ii), and a blowing agent configured to
evolve gas as part of or during the curing reaction, wherein the at
least one Part A and the at least one Part B are provided in at
least two respective receptacles configured to prevent
contamination, and the at least one Parts A and B are adapted to be
dispensed or released therefrom in cooperative manner facilitating
intimate contact and curing thereof, wherein the receptacle for the
at least one of Part A and Part B is thermally stable at an
elevated temperature of 123.degree. C. for a period in excess of 18
hours.
2. A curable composition as claimed in claim 1, wherein the
receptacles for the at least one Part A and the at least one Part B
are both thermally stable at the elevated temperature of
123.degree. C. for a period in excess of 18 hours.
3. A curable composition as claimed in any of claim 1, wherein the
receptacles are thermally stable at one or more of the following
conditions: an elevated temperature of 121.degree. C. for a period
of 30 hours, an elevated temperature of 123.degree. C. for a period
of 24 hours, an elevated temperature of 134.degree. C. for a period
of 6 hours, and an elevated temperature of 160.degree. C. for a
period of 1 hour.
4. (canceled)
5. (canceled)
6. A curable composition as claimed in claim 1, wherein the
receptacles comprise thermally stable receptacles, comprised of
materials selected from the group consisting of PE, PP PMP, COC's,
metal foil, glass, solid phase silicone polymer and the like and
from composites, laminates and combinations thereof which are
thermally stable at elevated temperature of 123.degree. C. for a
period in excess of 18 hours.
7. A curable composition as claimed in claim 1, wherein the one or
more alkenyl-containing polymers and the one or more SiH-containing
polymers are selected from the group consisting of silicones,
including siloxanes and modified siloxanes, polyurethanes (PU)
including polyester and polyether urethanes, elastomeric polyether
polyesters, polyglycolic acid, polyacetates such as ethyl vinyl
acetate, polyacrylate, polyacid derivatives of polysaccharides,
such as carboxyalkylcellulose, carboxyalkylchitosan and copolymers
thereof, and their hybrids including copolymers, entangled systems
and mixtures thereof.
8. (canceled)
9. (canceled)
10. (canceled)
11. (canceled)
12. (canceled)
13. (canceled)
14. A curable composition as claimed in claim 1, wherein the
composition is configured for medical or non-medical, dental or
non-dental use including use as dyes; preservatives; gels; foams;
aerosols; pharmaceuticals; adhesives; encapsulants; hair/skin care;
cosmetic use; dental use; release coatings; coatings; adhesives and
sealants; wound care including wound dressings; skin care including
scar reduction; cavity care; medical device encapsulation such as
electronic device encapsulation for biomedical applications; mould
making; orthopaedics; drug delivery systems including antimicrobial
systems; haemostatic and pharmaceutical systems; nutrition
including manufacture of foodstuffs; aerospace, marine and
submarine applications; ecologically sensitive applications;
confined or isolated organisms, or their habitats, or confined or
isolated medium or atmosphere such as those having low immunity;
sterile, clean or aseptic applications; germination or propagation
of living matter such as plants or organisms; including manufacture
and repair of equipment, apparatus or components for any of the
above and in particular aerospace, submarine sterile, clean or
aseptic, germination or propagation; including for use as foams,
aerosols, adhesives, release coatings, coatings, adhesives and
sealants, wound care in relation to NPWT, most particularly in a
sterile field or environment; including use as a wound filler or
wound packing material or cavity foam dressing, adhesive or
sealant; and use as a negative pressure wound therapy filling
material, adhesive or sealant, wherein the at least one Part A and
the at least one Part B are adapted to be dispensed in cooperative
manner facilitating intimate contact and curing thereof and
formation of a porous foam configured to transmit negative
pressure, adhering a negative pressure wound therapy drape or which
is substantially air-tight.
15. (canceled)
16. (canceled)
17. A method of preparing the composition as claimed in claim 1,
comprising: combining the one or more alkenyl-containing polymers,
the one or more SiH-containing polymers, the catalyst, and the
blowing agent to form the at least one Part A and the at least one
Part B; and sealing the at least one Part A and the at least one
Part B in the receptacles.
18. A method for sterilizing the composition as claimed in claim 1,
comprising subjecting the at least one of Part A and the at least
Part B, provided in or on a thermally stable receptacle to at least
one of: an elevated temperature in excess of 121.degree. C. for a
period of up to 28 hours, an elevated temperature of 123.degree. C.
for a period of up to 24 hours, and an elevated temperature of
160.degree. C. for a period of up to 100 minutes.
19. (canceled)
20. A method of preparing an elastomer comprising combining the at
least one Part A and the at least one Part B of the composition as
claimed in claim 1 with curing or crosslinking thereof.
21. (canceled)
22. (canceled)
23. An elastomer comprising the cured or crosslinked composition as
claimed in claim 1.
24. (canceled)
25. (canceled)
26. (canceled)
27. The medical or non-medical use of the composition as claimed in
claim 1 selected from the group consisting of use as dyes;
preservatives; gels; foams; aerosols; pharmaceuticals; adhesives;
encapsulants; hair/skin care; cosmetic use; dental use; release
coatings; coatings; adhesives and sealants; wound care including
wound dressings; skin care including scar reduction; cavity care;
medical device encapsulation such as electronic device
encapsulation for biomedical applications; mould making;
orthopaedics; drug delivery systems including antimicrobial
systems; haemostatic and pharmaceutical systems; nutrition
including manufacture of foodstuffs; aerospace, marine and
submarine applications; ecologically sensitive applications;
confined or isolated organisms, or their habitats, or confined or
isolated medium or atmosphere such as those having low immunity;
sterile, clean or aseptic applications; germination or propagation
of living matter such as plants or organisms; including manufacture
and repair of equipment, apparatus or components for any of the
above and in particular aerospace, submarine sterile, clean or
aseptic, germination or propagation; a wound filler or wound
packing material or cavity foam dressing, adhesive or sealant for
NPWT.
28. (canceled)
29. (canceled)
30. (canceled)
31. (canceled)
32. (canceled)
33. (canceled)
34. (canceled)
35. (canceled)
36. A method of providing negative pressure wound therapy,
comprising dispensing the composition as claimed in claim 1
directly or indirectly into a wound and allowing the composition to
foam and cure, sealing the wound including the foamed cured
composition, and applying negative pressure to the wound.
37. (canceled)
38. (canceled)
39. (canceled)
40. (canceled)
41. (canceled)
42. (canceled)
43. (canceled)
44. (canceled)
45. (canceled)
46. (canceled)
47. (canceled)
48. (canceled)
49. (canceled)
50. (canceled)
51. (canceled)
52. (canceled)
53. (canceled)
54. (canceled)
55. (canceled)
56. (canceled)
57. (canceled)
58. (canceled)
59. (canceled)
60. A curable composition as claimed in claim 1, wherein the
composition is terminally sterile, wherein a sterility level of the
composition corresponds to a sterility assurance level (SAL) of
10.sup.-6 such that the theoretical probability of there being a
viable microorganism present is equal to or less than
1.times.10.sup.-6.
61. A curable composition as claimed in claim 1, wherein: the one
or more alkenyl-containing polymers and the one or more
SiH-containing polymers are organosiloxanes; and curing by addition
of the alkenyl-containing polymer to the SiH-containing polymer
further comprises curing between organohydrogensiloxane units and
organoalkenylsiloxane units incorporated into polymeric,
copolymeric, entagled, and mixed polymer systems.
62. A curable composition as claimed in claim 61, wherein the one
or more alkenyl-containing polymers and the one or more
SiH-containing polymers are poly organosiloxanes.
63. A device for dispensing the curable composition as claimed in
claim 1, the device comprising a mixing head configured to receive
two or more cartridges comprising Parts A and B.
64. The device as claimed in claim 63, the device comprising a
double barreled syringe configured for loading with 40 g of the
polymers.
65. A method of providing negative pressure wound therapy, the
method comprising: dispensing a terminally sterile foamable
composition into at least a portion of a wound site, wherein the
foamable composition is configured to form a porous foam material
configured to transmit negative pressure; sealing the wound site
with a substantially fluid-tight seal; and applying negative
pressure to the wound site from a source of negative pressure.
66. The method of claim 65, further comprising covering the wound
site with the substantially fluid-tight drape, the drape covering
at least a portion of the dispensed terminally sterile composition
and forming a fluid-tight seal over the wound site.
67. The method of claim 65, wherein the composition comprises a
first part and a second part, the first and second parts configured
to be combined to form the porous form material.
68. The method of claim 67, further comprising: releasing the first
part from a support and exposing the first part; exposing the
second part; and covering the wound site with the drape and
adhering the drape around the wound site, thereby causing the
exposed first and second parts to come into contact.
69. A NPWT kit comprising a substantially fluid-tight wound
dressing, a dispensable or releasable curable or cured foamable
composition as claimed in claim 1, and a port configured to be
connected to a source of negative pressure.
70. The elastomer as claimed in claim 23, wherein the elastomer
comprises wound dressing.
Description
[0001] Embodiments of the present invention relate to a two part,
curable composition, methods for preparing the composition,
manufacture thereof and methods for sterilisation thereof, medical
and non-medical use thereof, methods for use or therapy therewith,
a device incorporating the composition, and a precursor therefor
including its sterilisable precursor composition. In particular,
certain embodiments of the invention relates to a sterilisable or
sterile composition for medical use, particularly in wound therapy,
more particularly as a wound packing material or filler which can
be shaped and configured to the shape of a wound, or an adhesive or
sealant for a wound dressing, most particularly for application in
negative pressure wound therapy (NPWT).
BACKGROUND OF THE INVENTION
[0002] NPWT is a relatively new treatment for open wounds. Briefly,
negative pressure therapy can assist in the closure and healing of
many forms of "hard to heal" wounds by reducing tissue oedema;
encouraging blood flow and granular tissue formation; removing
excess exudate and may reduce bacterial load (and thus infection
risk). In addition, the therapy allows for less disturbance of a
wound leading to more rapid healing. TNP therapy systems may also
assist on the healing of surgically closed wounds by removing fluid
and by helping to stabilise the tissue in the apposed position of
closure. A further beneficial use of TNP therapy can be found in
grafts and flaps where removal of excess fluid is important and
close proximity of the graft to tissue is required in order to
ensure tissue viability.
[0003] Typically in NPWT the wound cavity or surface is filled or
covered with a material that allows the transmission of a partial
vacuum (i.e. does not completely collapse) to the wound bed when a
negative pressure is applied to the wound area, and also allows
fluids to pass from the wound bed towards the source of negative
pressure. There are two primary approaches to NPWT, i.e. gauze or
foam types. The gauze type involves the use of a drain wrapped in
gauze topped by a sealed dressing. The foam type involves the use
of foam placed over or in the wound, also topped by a sealed
dressing. One embodiment is directed primarily towards the foam
type of NPWT. Further embodiments are directed towards either the
foam or gauze type of NPWT, or to a further type of NPWT which uses
a sealed dressing as a combination or preformed with additional
absorption or distribution layers or the like.
[0004] A good material for the foam based NPWT application which
offers good resistance to compression under loading, is
hydrophobic, reticulated polyurethane foam of high free internal
volume.
[0005] However articles of high free internal volume tend to be
poorly drapeable due to the requirement for their structure to
mechanically support their high free internal volume, and this is
the case in foams applied in NPWT.
[0006] Therefore packing material for use in NPWT must be shaped to
fit the wound to be packed. This is typically achieved by the
medical practitioner (physician or nurse) cutting a preformed block
of foam to approximately fit the wound using a scalpel, knife or
scissors. This operation can be complex and has the potential to
introduce contamination, moreover is time consuming and messy for
the medical practitioner, and indeed can be dangerous with the
possibility of particulate foam contaminating the wound site or of
an accident during the cutting process. Accordingly the process of
shaping the wound dressing is currently an unaddressed problem in
the field of NPWT.
[0007] Castable compositions are known for use in wound care.
WO2009/156709 discloses a topical negative pressure, or vacuum,
wound therapy wound covering element or drape constructed of
silicone or polyurethane based materials, which provides a
substantially air-tight seal over a wound, having a vacuum
connection tube or line for connection to a negative pressure
source moulded or glued in place to reduce the likelihood of
negative pressure leakage. The drape may be manufactured by casting
a two-part heat curable silicone elastomer over the vacuum line,
located in a mould. The resulting drape may be sterilised by
irradiation and packaged in sterile form until required for use by
placing over a foam or gauze wound filler.
[0008] An RTV-2 (addition cure two-part room temperature
vulcanizing) silicone foam wound dressing, Cavi-Care, is sold
non-sterile. U.S. Pat. No. 5,153,231 discloses the composition
which is capable of providing a low density foamed medical dressing
by releasing two components into a mixing vessel by rupture of
their individual packaging, mixing and dispensing or casting onto a
surface such as an open wound and allowing the mixture to cure at
room temperature.
[0009] It would be useful to provide a castable in-situ wound
filler in the form of an RTV-2 silicone foam. It would also be
useful to provide a castable in-situ adhesive or sealant for a NPWT
drape or dressing. The problem is that for an RTV-2 wound filler,
adhesive, sealant or the like to be viable the two part system must
be available sterile.
[0010] Where a product for medical use is required to be sterile at
point of use, it is a well accepted principle that it should be
manufactured using aseptic processing only when terminal
sterilisation is not feasible. To ensure the highest levels of
sterility assurance for a medical product, it should therefore be
terminally sterilised in its final packaging.
[0011] Although sterile foamed wound dressing materials are
available such as Allevyn.TM., a polyurethane foam wound covering
element, and black foam ("Granufoam"), a polyurethane wound filler,
supplied packaged in a peel pouch, no two-part RTV-2 silicone
composition or indeed any RTV-2 composition, foamable or otherwise,
appears to be available sterile, as the two part system prior to
curing, either terminally sterilised in primary packaging or
sterilised and then aseptically packaged. Furthermore a process for
sterilising these systems does not appear to be available.
[0012] One object of the invention is to provide an improved
terminally sterile RTV-2 foamable silicone composition. It is a
further object to provide an improved, terminally sterile, wound
filler which can be conformed to the shape of a wound cavity. It is
a further object to provide a terminally sterile RTV-2 non-foamable
or partially foamable silicone composition. It is a further object
to provide a terminally sterile adhesive or sealant which can be
conformed about a wound cavity.
[0013] In attempting to find a route to sterilise a two part
foamable curable silicone composition which could be cast into a
desired shape and cured in situ to form a shaped three dimensional
body, we found that most of the sterilisation techniques that would
be typically employed to sterilise a material are unsuitable or are
incapable of sterilising the composition without degradation. The
same was true in attempting to find a route to sterilise a two part
adhesive or sealant.
[0014] Established terminal sterilisation procedures give a
10.sup.6 confidence in its sterility. We investigated heat as a
route to sterilise these reactive materials.
[0015] Medical instruments such as scalpels etc. are typically
steam sterilised using autoclaves. Typical steam sterilization
cycles include a hold at 121.degree. C. for a minimum of 15 minutes
or a hold at 134.degree. C. for a minimum of 3 minutes.
Sterilisation of packaged items, in the absence of water, follow
dry heat sterilisation processes which require higher temperatures
and/or longer hold times. Various temperatures and hold times are
known dependent on the materials and sterilization equipment
employed. The US Pharmacopeia indicates 160-170.degree. C. with a
hold of 2-4 hours, the British Pharmacopeia indicates not less than
160.degree. C. with a hold of not less than 1 hour and the
Pharmacopeia Nordica states 180.degree. C. with a hold of 30
minutes.
[0016] However the Tg and softening point of most commercially
available thermoplastics which would be considered for packaging is
below 160.degree. C. The lack of readily available packaging which
can withstand the required heat cycle is an obstacle to the use of
a heat sterilisation method for sterilising RTV-2 compositions.
Whilst some softening and reforming of packaging might be
considered to be acceptable if resulting in intact packaging after
sterilisation, the softened packaging might be permeable to or
damage the performance of composition constituents or might allow
the possibility of contamination thereof. Any external influence
might disadvantageously reduce the effectiveness of the resulting
cured composition.
BRIEF DESCRIPTION OF THE INVENTION
[0017] We have now found a route for sterilisation of packaged
RTV-2 compositions, for which both the composition itself and the
selected packaging are capable of withstanding conditions of
elevated temperature for periods sufficient for sterilisation,
without degradation thereof.
[0018] Accordingly, there is provided according to a first
embodiment of the present invention a curable composition,
comprising or apportioned between at least one Part A and at least
one Part B, the Parts sealed within barrier means in manner to
prevent contamination thereof, the composition comprising:
(i) one or more alkenyl-containing prepolymers having at least one
alkenyl moiety per molecule, (ii) one or more SiH-containing
prepolymers having at least one SiH unit per molecule, and
additionally: (iii) a catalyst for curing by addition of
alkenyl-containing prepolymer (i) to SiH-containing prepolymer
(ii), wherein the at least one Part A and at least one Part B are
provided within or upon at least two respective receptacles or
supports and are adapted to be dispensed or released therefrom in
cooperative manner facilitating intimate contact and curing
thereof, wherein the receptacle(s) or support(s) for at least one
of Part A and Part B is thermally stable at elevated temperature of
or in excess of 123.degree. C. for a period in excess of 18
hours.
[0019] In a first preferred embodiment of the present invention
there is provided a curable composition, comprising or apportioned
between at least one Part A and at least one Part B, the Parts
sealed within barrier means in manner to prevent contamination
thereof, the composition comprising:
(i) one or more alkenyl-containing prepolymers having at least one
alkenyl moiety per molecule, (ii) one or more SiH-containing
prepolymers having at least one SiH unit per molecule, and
additionally: (iii) a catalyst for curing by addition of
alkenyl-containing prepolymer (i) to SiH-containing prepolymer
(ii), wherein the at least one Part A and at least one Part B are
provided within at least two respective receptacles and are adapted
to be dispensed therefrom in cooperative manner facilitating
intimate contact and curing thereof, wherein the receptacle(s) for
at least one of Part A and Part B is thermally stable at elevated
temperature of or in excess of 123.degree. C. for a period in
excess of 18 hours.
[0020] In a further preferred embodiment of the invention there is
provided a foamable curable composition for use as a negative
pressure wound therapy wound filling material, comprising or
apportioned between at least one Part A and at least one Part B,
the Parts sealed within barrier means in manner to prevent
contamination thereof, the composition comprising:
(i) one or more alkenyl-containing prepolymers having at least one
alkenyl moiety per molecule, (ii) one or more SiH-containing
prepolymers having at least one SiH unit per molecule, and
additionally: (iii) a catalyst for curing by addition of
alkenyl-containing prepolymer (i) to SiH-containing prepolymer
(ii), (iv) a blowing agent, wherein the at least one Part A and at
least one Part B are provided within at least two respective
receptacles and are adapted to be dispensed therefrom in
cooperative manner facilitating intimate contact and curing
thereof, and formation of a porous foam which is suitable for
transmitting a negative pressure to a wound surface. Preferably the
receptacle(s) for at least one of Part A and Part B is thermally
stable at elevated temperature of or in excess of 123.degree. C.
for a period in excess of 18 hours. Preferably the at least one
Part A and at least one Part B are adapted to be dispensed in
cooperative manner facilitating intimate contact and curing thereof
and formation of a porous foam which is capable of transmitting
negative pressure.
[0021] In a further preferred embodiment of the invention there is
provided a curable composition, comprising or apportioned between
at least one Part A and at least one Part B, the Parts sealed
within barrier means in manner to prevent contamination thereof,
the composition comprising:
(i) one or more alkenyl-containing prepolymers having at least one
alkenyl moiety per molecule, (ii) one or more SiH-containing
prepolymers having at least one SiH unit per molecule, and
additionally: (iii) a catalyst for curing by addition of
alkenyl-containing prepolymer (i) to SiH-containing prepolymer
(ii), wherein the at least one Part A and at least one Part B are
provided upon at least two respective supports and are adapted to
be released therefrom in cooperative manner facilitating intimate
contact and curing thereof, wherein the support(s) for at least one
of Part A and Part B is thermally stable at elevated temperature of
or in excess of 123.degree. C. for a period in excess of 18
hours.
[0022] In the above embodiments, the composition is sterilisable or
is sterile. Preferably the composition is provided in packaged
form, the receptacles or supports and any other integral parts
sealed within further barrier means. The composition may be
packaged prior to sterilisation or may be maintained under sterile
conditions and packaged subsequent to sterilisation. Suitably
therefore the composition is packaged as a double wrapped item,
which allows for the removal of the first layer of sterile sealed
packaging to reveal a cartridge or syringe which is completely
sterile inside and out, facilitating entry into a sterile
environment. If the product is only available in a single sterile
packaging it would mean the external surface of the dispenser was
contaminated and therefore it would not be possible to take into a
sterile field
[0023] Preferably the receptacle or support(s) for at least one of
part A and part B as hereinbefore defined is thermally stable under
conditions suitable for dry-heat sterilisation of the composition
part. Preferably the prepolymers (i) and (ii) and catalyst (iii)
are apportioned in at least two parts A and B in manner to provide
respective parts A and B which in isolation are not reactive at
ambient temperature. Preferably the Part A and Part B are provided
sealed within receptacles or on supports in substantial absence of
air within the receptacles or on the supports. Preferably
receptacles or supports and any other components in or on which the
Parts are supported are moisture and air and contaminant
impermeable. Preferably the Part A and Part B are provided sealed
within receptacles or on supports consisting exclusively of primary
contact packaging materials that are capable of containing the
composition at elevated temperature as herenbefore defined without
thermal degradation thereof, and moreover which are capable of
containing the composition at elevated temperature as herenbefore
defined in manner so as not to contaminate the composition, i.e. do
not interact with or degrade the respective Parts sealed therein or
thereon.
[0024] We have found that the at least one Part A and/or at least
one Part B as hereinbefore defined, are both stable and do not
pre-react and also do not suffer contamination by or leakage of
material from their respective receptacle or support at elevated
temperature in excess of 110.degree. C., and potentially up to
250.degree. C. In the case that at least one of Part A and Part B
is capable of sterilisation by an alternative technique, then only
the other(s) of Part A and Part B need be packaged and sterilised.
Alternatively the receptacles or supports for both of the at least
one Part A and at least one Part B are thermally stable at elevated
temperature of 123.degree. C. for a period in excess of 18 hours.
This allows both or all parts of the composition to be sterilised
by thermal technique.
DETAILED DESCRIPTION OF THE INVENTION
[0025] We have surprisingly found that while a standard 121.degree.
C. autoclave cycle for 15 minutes will not sterilise the
composition, temperatures which are not as aggressive as the
Pharmacopeiea standard 160.degree. C. for 1 hour, for dry heat
sterilisation, but when used for a sufficient period of time, in
the region of 123.degree. C. for 24 hours or more or 134.degree. C.
for 6 hours or more, nevertheless achieve the required level of
sterilisation by the dry heat method. These temperatures are
therefore emminently suited for providing a terminally sterile
RTV-2 composition, hitherto unknown and unavailable.
[0026] Embodiments of the invention have application to any RTV,
LTV or HTV compositions, which may comprise 2 or more components or
Parts. Preferably the composition is an RTV-2, LTV-2 or HTV-2
composition, foamable or otherwise, for any envisaged use requiring
sterility. The addition cure chemistry of 2-part RTV, LTV and HTV
compositions is based on the hydrosilylation of vinyl functional
prepolymers by Si-hydride functional prepolymers. Room temperature
vulcanising is typically taken to mean the system cures below
50.degree. C. Low temperature vulcanising is taken to mean the
system cures in the range from 50.degree. C. to 130.degree. C. High
temperature vulcanising is taken to mean the system cures at a
temperature in excess of 130.degree. C. More preferably the
composition is an RTV-2 composition.
[0027] Embodiments of the invention may also have application to
any two or more Part curable composition for which the Parts are
adapted to be dispensed or released in cooperative manner
facilitating intimate contact and curing thereof. Such Parts are
therefore suitably fluid phase or capable of fluid behaviour under
acceptable dispensing or release conditions or capable of wetting
out a surface or material to which they are dispensed or released,
for example Part A and Part B are capable of mutual wetting out
when cooperatively dispensed or cooperatively released.
[0028] Suitably therefore the composition is packaged in a range of
materials which would not withstand the standard 160.degree. C./1
hour cycle, and yet will withstand terminal heat sterilisation
conditions, and therefore removes the constraint limiting the
design of the packaging and increases the commercial viability of
the packaging. Furthermore heat sterilisation at this temperature
is in the capability of most autoclaves or ovens. In a preferred
embodiment a receptacle or support is thermally stable at elevated
temperature in the range 123.degree. C. to 145.degree. C. for a
period in excess of 18 hours down to 4 hours.
[0029] Polymers can often withstand elevated temperatures around or
in excess of their thermal stability threshold, for short periods,
but not for continuous prolonged periods. The dry heat
sterilisation temperature can therefore be correlated against both
the time at sterilisation temperature required to achieve 100%
microbial kill, (hereinafter reference to 100% microbial kill is to
the technically termed 10.sup.6 microbial kill (99.9999%)) and
against the time at elevated temperature which the composition
packaging is capable of withstanding without becoming thermally
unstable. That the kill time and thermal stability time are related
in similar manner to the sterilising temperature is fortuitous, and
this underlies certain preferred embodiments.
[0030] Reference to dry heat sterilisation is to the sterilisation
regime taking place directly at the composition Part. Accordingly
the composition may be sterilised in a conventional oven or
autoclave at ambient or elevated pressure with steam present, but
the manner of packaging is resilient to steam penetration and
thereby prevents steam contacting the composition directly, whereby
the effective sterilisation is a dry heat sterilisation. The
conditions prevailing outside the composition packaging are
therefore irrelevant to those prevailing within the packaging, as
steam does not penetrate the packaging, Accordingly a composition
which is subject to dry heat sterilisation conditions but which
includes water or moisture, would undergo a steam sterilisation
regime. Conversely a composition which is subject to steam
sterilisation conditions but which has no water or moisture
present, would undergo an in situ dry heat sterilisation regime.
Accordingly references to dry heat sterilisation as being
unsuccessful are misleading, in the case that the in situ
sterilisation regime conducted was in fact steam sterilisation.
[0031] Preferably either or both Parts of the composition have
substantially no water, steam or air present and undergo an in situ
dry heat sterilisation. More preferably Part B has substantially no
water, steam or air present and undergo an in situ dry heat
sterilisation. Part A may have water, moisture or air present or
absent and may undergo steam or dry heat sterilisation.
[0032] Preferably the receptacles or supports are thermally stable
at elevated temperature in the range 110 C to 250 C for a period in
excess of 15 minutes, more preferably in the range of 110 C to 160
C for a period in excess of 30 minutes, more preferably in the
range of 110 C to 155 C for a period in excess of 1 hour, more
preferably in the range of 110 C to 145 C for a period in excess of
3 hours, more preferably in the range of 110 C to 135 C for a
period in excess of 5 hours, more preferably in the range of 110 C
to 120 C for a period in excess of 10 hours. This is represented
graphically as the area above the line in the Graph 1 below.
(relable from FIG. 1)
[0033] Preferably the receptacles or supports are thermally stable
at elevated temperature of 123.degree. C. for a period of 18 hours
or more. More preferably the receptacles or supports are thermally
stable at any one or more of the following cycles selected from
elevated temperature of 121.degree. C. for a period of 30 hours,
elevated temperature of 123.degree. C. for a period of 24 hours,
elevated temperature of 134.degree. C. for a period of 6 hours and
elevated temperature of 160.degree. C. for a period of 1 hour.
Cycles intermediate these values can be envisaged such as elevated
temperature of 155.degree. C. for a period of 2 hours, elevated
temperature of 145.degree. C. for a period of 4 hours.
[0034] The hereinbefore defined thermal cycles may be useful to
determine intermediate elevated temperature and time combinations
which would fall on or about an exponential curve drawn between the
ends of the defined range as indicated in the Graph 2 below (not to
scale). Graph 2 (relable from FIG. 1)
[0035] Receptacles or supports which are thermally stable in the
range between a first elevated temperature from a first period up
to a second elevated temperature for up to a second period, are
required to be stable at a single temperature and time combination
in that range although they may also be stable across the entire
range.
[0036] Reference herein to a thermally stable receptacle or support
is to such article which exhibits no detectable change in one or
more of the following property at the hereinbefore or hereinbelow
defined temperature for the hereinbefore or hereinbelow defined
period: melt flow index (MFI); or for which one of the following
temperatures is not exceeded by the hereinbefore defined
temperature and time: vicat (A) softening temperature, product
specification maximum working temperature, thermal instability
threshold temperature and the like.
[0037] Thermoplastics do not have a definite melting point which
precisely marks the transition from fluid to solid, but rather
undergo a gradual softening as temperature increases, or as time
held at elevated temperature increases. For example polycarbonate
has a Tg of about 150.degree. C. and Vicat softening temperature
(10N load) of 157.degree. C., and softens gradually around this
temperature. Melt Flow Index is a measure of the ease of flow of
the melt of a thermoplastic polymer (ASTM D1238, ISO 1133). Vicat
softening point is the determination of softening point for such
materials that have no definite melting point. It is taken as the
temperature at which the specimen is penetrated to a depth of 1 mm
by a flat-ended needle with a 1 square mm circular or square
cross-section loaded with a 10N load (Vicat A). See Polymer
Handbook, ed. J. Brandrup and E. H. Immergut, John Wiley & Sons
Inc., New York, 2.sup.nd edn., 1975, pp. 111-144, the contents of
which are incorporated herein by reference.
[0038] Receptacles or supports may therefore comprise any suitable
material which provides a barrier to microbial infection and is
thermally stable at temperatures in excess of 123.degree. C. up to
160.degree. C. and even up to 250.degree. C. Certain materials such
as some polyethylene (PE) for example polyethylene terephthalate
(PET), PE (Vicat softening temperature 94-107.degree. C., ultra
high MW PE (UHMPE) (Vicat softening temperature 80-100.degree. C.),
certain grades of polypropylene (PP) are of low thermal stability
and are therefore not suitable for the invention. Certain preferred
embodiments use of known and novel high temperature stable
materials such as polycarbonates (PC) (Vicat softening temperature
157.degree. C.), isotactic polypropylene (iPP) (Tg -13.degree. C.
to 0.degree. C., Vicat softening temperature 138-155.degree. C.),
atactic polypropylene (aPP) (Tg -18.degree. C. to -5.degree. C.),
polymethylpentene (PMP) and cyclic olefin copolymers (COC) (Tg and
Vicat 80.degree. C.-180.degree. C.) which are disclosed as stable
up to 170.degree. C. Because COC is amorphous, it maintains
stiffness at elevated temperature far better than semicrystalline
polymers such as PE or PP. COC maintains high stiffness up to
temperatures within 10.degree. to 15.degree. C. of its Tg. Because
iPP has Tg remote from its Vicat softening temperature it has
superior maintenance of mechanical properties at elevated
temperature to COC and like materials having proximal Tg and Vicat
softening temperature.
[0039] Preferably thermally stable receptacles, supports and any
seals and cooperating parts are comprised of materials selected
from metals, glass, and polymers and the like and from composites,
laminates and combinations thereof which are thermally stable at
elevated temperature of 123 C for a period of or in excess of 18
hours; preferably from PE, PP PMP, COC's, metal foil, glass, solid
phase silicone polymer and the like and from composites, laminates
and combinations thereof which are thermally stable at elevated
temperature of 123 C for a period in excess of 18 hours; more
preferably from:
high temperature stable PE such as high density PE (HDPE) which can
withstand temperatures of 120.degree. C. for short periods, or
110.degree. C. continuously, and cross linked PE (PEX or XLPE) with
reduced flow tendency at up to 120.degree.-150.degree. C.; high
temperature stable PP (HTSPP) such as isotactic PP (iPP Vicat
softening temperature 138-155.degree. C., W. A. Lee and R. A
Rutherford "The glass transition temperatures of polymers" in
Polymer Handbook, ed. J. Brandrup and E. H. Immergut, John Wiley
& Sons Inc., New York, 2.sup.nd edn., 1975, pp. V-27, the
contents of which are incorporated herein by reference.); atactic
PP; commercially available PP rated to 140.degree. C., Tg approx
-10.degree. C.; PCs (Vicat softening temperature 157 C);
polymethylpentene (PMP, for example available as 50 ml squat form
beaker, temperature resistant to 180.degree. C., Fisher Scientific,
Product Code: BNH-740-070E); high temperature stable COC's (Tg and
Vicat 110.degree. C.-180.degree. C.); metal foil for example
aluminium; glass; solid phase silicone polymer; and the like; and
from composites, laminates and combinations thereof which are
thermally stable as hereinbefore defined. PCs, HTSPP, COCs and
glass are preferred materials.
[0040] More preferably compositions comprise receptacle or support
material having thermal stability at temperatures in the range as
follows: 155.degree. C. to 160.degree. C.: COCs, PCs, metal foil,
glass, silicone polymer; 110.degree. C. to 155.degree. C.: COCs,
PCs, PEX or XLPE, isotactic PP, HDPE.
[0041] Suitably the barrier means, for example a receptacle seal,
closure, cap, lid or the like is thermally stable as hereinbefore
defined. Certain compositions may be suitable for use together with
cooperating parts facilitating containment, dispensing or release
of the at least one Part A and at least one Part B and intimate
contact thereof. Such cooperating parts may optionally be thermally
stable and dry heat sterilisable as hereinbefore defined or steam
sterilisable, or may be provided for assembly with cooperating
parts during use, and parts may be sterilised by alternative means
and are not required to be thermally stable as hereinbefore
defined. In the case that the packaged composition comprises
integral cooperating parts, any such parts are suitably thermally
stable as hereinbefore defined. Integral cooperating parts include
closures such as lids, caps, seals such as O-rings, release means
such as pistons, plungers and the like.
[0042] Suitably the composition including receptacles or supports
and any integral cooperating means is packaged in a further outer
(secondary) packaging which is resistant to EO or is steam
permeable, which is suitable for sterilisation in usual manner.
Thereby both the interior and exterior of the composition are
maintained sterile, and can be carried into a sterile field and
opened.
[0043] We have determined that some compositions may be susceptible
to contamination at thermal sterilisation conditions, by contact
with receptacle and cooperating parts. Accordingly cooperating
parts which are themselves thermally stable have been found to
contaminate the Part A and/or Part B components at elevated
temperature. Contamination takes the form of one or more of visual
contamination, chemical contamination and the like. Visual
contamination is for example discoloration or formation of
agglomerates. Chemical contamination is for example one or more of
viscosity change, reducing activity of or deactivating components
which take part in curing or foaming reaction.
[0044] A preferred composition comprises Part A and Part B as
hereinbefore defined provided within or upon receptacles or
supports wherein cooperating parts for such receptacles or supports
are thermally stable at elevated temperature of 123.degree. C. for
a period in excess of 18 hours, and optionally at preferred
elevated temperature conditions as hereinbefore defined.
[0045] Preferably a composition can comprise Part A and Part B as
hereinbefore defined provided within or upon receptacles or
supports wherein Part A and Part B are thermally stable at elevated
temperature of 123.degree. C. for a period of or in excess of 18
hours, and optionally at preferred elevated temperature conditions
as hereinbefore defined, in the presence of or in contact with
cooperating parts for such receptacles or supports. Preferably such
cooperating parts are substantially inert in the presence of Part A
and/or Part B under such conditions, i.e are both thermally stable
and also remain intact under the thermal sterilisation conditions,
i.e do not leach out any component.
[0046] A receptacle or support may be flexible or rigid. A rigid
receptacle or support is suitably any vial or cartridge as known in
the art. A flexible receptacle or support for example may be formed
from a laminate of metal foil having on each face thereof a film of
thermally stable polymer as hereinbefore defined, which can be
heat-sealed or laminated.
[0047] A receptacle may comprise a portion which is intended to
remain intact, and a portion which is intended for rupture or
penetration in manner to release the composition Part sealed
therein. A receptacle may therefore comprise a combination of
different thermally stable materials or a combination of different
thicknesses of a thermally stable material.
[0048] Receptacles may be manually ruptured at weakened portions
thereof, or mechanically ruptured or penetrated by physical means
for example provided in a device for penetration and cooperative
dispensing of composition parts. Suitable physical means include
needles, spikes, punches such as bayonet caps, push-fit opening
means and the like.
[0049] Reference herein to Parts A and B being present in
receptacles in substantial absence of air or moisture, is suitably
to air or moisture presenting less than 10% of the receptacle
volume, preferably less than 5% of the receptacle volume. Air or
moisture is suitably absent from any space above or about the
composition, i.e headspace or the like, or such space is
substantially absent. Air or moisture may additionally be absent
from the composition itself, i.e the composition may be degassed or
sparged or the like to remove air. It will be appreciated that the
objective of providing an absence of air is to provide an absence
of oxygen and moisture vapour.
[0050] Accordingly a substantial absence of air may be provided in
known manner by displacement and/or removal or air. Displacement of
air is suitably by means of purging the space about the
composition, such as the headspace present above the composition
within the barrier means, with a suitable inert gas; and/or
sparging the composition with a suitable inert gas. Removal of air
is suitably by means of providing the Part in a receptacle of
substantially equal volume to the Part volume in manner to
substantially eliminate any headspace. A suitable inert gas is
argon or nitrogen or the like. Purging displaces air above the Part
with inert gas. Sparging displaces air within the Part with inert
gas. Matching volumes removes air above the Part.
[0051] Reference to cooperative dispensing as hereinbefore defined
is to any method by which one or more Parts is dispensed
simultaneously with and into direct contact with the other one or
more Parts, preferably with simultaneous mixing. Preferably
receptacles are adapted to be received within a device providing
means to cooperatively release the respective Parts into an
integral mixing chamber or nozzle with integral advancing mixing
means for ejecting mixed composition from the device. Suitably
ejection means is provided for dispensing of composition from
receptacles, for example pistons, plungers and the like.
Embodiments herein may be of particular advantage in ejecting
composition directly into or onto the site of application or into a
mould prior to application, thereby minimising the risk of
contamination or infection. This has further advantages of
enhancing accuracy of administering composition.
[0052] In a particular advantage of the invention certain
compositions may be suitable for cooperatively dispensing into a
desired location or cavity, curing and retaining a desired
positioning or shape. Preferably the composition is suitable for
dispensing into or about a wound. Preferably the composition is
suitable for dispensing or releasing in a sterile field or
environment. This is particularly advantageous in the case of
medical applications for example within the sterile field of an
operating theatre allowing the possibility to dispense directly or
indirectly, for example via a mould, into a wound in a sterile
field or environment. This avoids the need to contact the
composition once dispensed, for example for positioning or shaping,
and minimises the risk of introducing infection.
[0053] An embodiment of the RTV-2 composition may comprise any
prepolymers that follow a hydrosilylation reaction. One prepolymer
preferably contains alkenyl groups, the other preferably contains
Si--H moieties. The group of siloxane polymers is based on a
structure comprising alternate silicon and oxygen atoms with
various organic moieties attached to the silicon. Curing can be
defined as a treatment that decreases the flow of an elastomer.
This change is generally brought about by linking reactions between
polymer molecules. Where the silicon hydride (Si--H) moiety is part
of a polysiloxane, it is possible for the alkenyl group to either
be part of a siloxane prepolymer or otherwise part of a
non-siloxane prepolymer. The position of the alkenyl functional
group is not critical and it may be either at the molecular chain
terminals or in non-terminal positions along the molecular
chain.
[0054] Prepolymers (i) and (ii) are commercially available or may
be obtained by known techniques. Suitably prepolymers (i) and/or
(ii) are independently selected from known and novel fluid phase
homopolymeric, and copolymeric prepolymers, and their entangled
systems and mixtures thereof. The compositions, in turn, cure to
form copolymers, and may also include their entangled systems and
mixtures with other non-reactive prepolymers if present in the
composition.
[0055] The term fluid phase is intended to include prepolymers
which can exist in fluid phase or behave as fluids, i.e the
sterilised prepolymers are capable of admixture to form the
respective Part.
[0056] Copolymeric prepolymers include all hybrids derived from two
or more monomeric species, including alternating, periodic,
statistical, random, block, linear, branched, star, graft and
pendant copolymers. Entangled systems include interpenetrating
networks (IPNs) and semi-interpenetrating networks (SIPNs). It is
also the case that these prepolymers can incorporate both organic
and inorganic moieties.
[0057] Preferably prepolymers (i) and (ii) are selected from
silicones, including siloxanes and modified siloxanes,
polyurethanes (PU) including polyester and polyether urethanes,
elastomeric polyether polyesters, polyglycolic acid, polyacetates
such as ethyl vinyl acetate, polyacrylate, polyacid derivatives of
polysaccharides, such as carboxyalkylcellulose,
carboxyalkylchitosan and copolymers thereof, and their hybrids
including copolymers, entangled systems and mixtures thereof.
[0058] More preferably the curable composition makes use of an
addition cure reaction between organohydrogensiloxane units and
organoalkenylsiloxane units. These units may be incorporated into a
wide range of polymeric, copolymeric, entangled and mixed
prepolymers as hereinbefore defined. Preferred siloxane prepolymers
(i) and (ii) therefore include these respective units and are more
preferably polyorganosiloxanes.
[0059] Examples of hybrid organic-inorganic polymeric systems that
have used both siloxane and organic units include: acrylate
functionalized siloxane copolymers, which have found use in contact
lenses (U.S. Pat. No. 3,808,178); hybrid grafts where organic
polymers are grafted onto a polysiloxane chain or where siloxanes
are grafted onto organic polymers, for example in silane graft
technology for cross linkable HDPE (U.S. Pat. No. 3,646,155) where
hybrid grafts have been used to allow the cross linking of organic
polymers through siloxane bond formation; hybrid block copolymers
for example silicone-polycarbonate block copolymers (U.S. Pat. No.
3,274,155); and copolymers of hybrids of silicone and ethylene
copolymers, cross-linked with vinyl-containing silicone copolymers
which have found use in coating textiles (US 2005/0100692); IPNs
represent a special class of hybrid polymeric systems, these
systems use a combination of mechanical entanglement and
crosslinking in which one polymer is cured about another; these
include thermoplastics entangled with platinum catalyzed addition
cure silicones such as silicone-urethane IPNs and semi-IPNs
including silicone-urethane and silicone-polyamide systems which
are of general application or have found specific use in coating
textiles (U.S. Pat. No. 4,714,739, U.S. Pat. No. 7,543,843);
hydrophilic components immobilised in a silicone polymer (U.S. Pat.
No. 5,397,848) which have found use as contact lens material; and
silicone polymer cured about a non-reactive polymer of comparable
adhesion, which have found use in coating textiles (U.S. Pat. No.
7,132,170).
[0060] Prepolymers may also be selected from modified silicones
(MS) which find use as adhesives in catheter tubing and the
like.
[0061] Preferred compositions comprise a polydiorganosiloxane
prepolymer (i) and/or (ii) and/or their respective combinations
with the aforementioned prepolymers. A composition in which
prepolymers comprise or consist essentially of polydiorganosiloxane
prepolymers (i) and (ii) has particular advantages, for example in
applications where low toxicity is an advantage, preferably in
medical or dental applications or in non-medical or non-dental
applications requiring low toxicity or favorable
biocompatibility.
[0062] Prepolymer (i) and (ii) may comprise respective
alkenyl-containing units and organohydrogensiloxane units situated
along the length of prepolymer chains, and/or as prepolymer chain
end-capping units or a combination thereof. Prepolymer (i) in-chain
and end-capping alkenyl units preferably comprise alkenyl group or
moiety R.sup.Alk selected from C.sub.2-20 alkenyl optionally
substituted or including one or more aryl groups or moieties.
R.sup.Alk may comprise terminal or non terminal unsaturation, and
may be of the formula i-I:
--R.sup.Alk1--CR.sup.Alk1.dbd.CR.sup.Alk2.sub.2 (i-I)
in which the groups R.sup.Alk1 and R.sup.Alk2 are independently
selected from H, C.sub.1-20 alkyl and C.sub.5-20 aryl groups and
combinations thereof and a moiety R.sup.Alk1 is selected from a
single bond, C.sub.1-20 alkyl and C.sub.5-20 aryl groups and
combinations thereof. One of R.sup.Alk2 may be a moiety linking to
polymer chain. More preferably each R.sup.Alk is independently
selected from vinyl, allyl, propenyl, and from terminally and
non-terminally unsaturated butenyl, pentenyl, hexenyl, heptenyl,
octenyl, nonenyl and decenyl groups, most preferably selected from
vinyl and hexenyl groups and moieties.
[0063] Preferably prepolymer (i) comprises a polydiorganosiloxane
polymer or copolymer comprising alkenyl-containing units of the
formula (i-II):
.ident.Si--R.sup.Alk, (i-II)
more particularly of the formula (i-III) and/or (i-IV):
--O--Si R.sup.1R.sup.Alk--O-- (i-III)
--O--Si R.sup.1.sub.2R.sup.Alk (i-IV)
wherein R.sup.Alk is as hereinbefore defined and one or more groups
R.sup.1 are organo groups suitably independently selected from
alkyl and aryl groups, more preferably optionally fluorinated
C.sub.1-20 alkyl and cycloalkyl and C.sub.5-20 aryl groups and
combinations thereof, for example from methyl, ethyl, propyl,
butyl, pentyl, hexyl, heptyl, octyl, nonyl and/or decyl groups.
[0064] More particularly prepolymer (i) is selected from the
formula i-V and i-VI:
P.sup.i-O--Si R.sup.1R.sup.Alk--O--P.sup.i i-V:
P.sup.i-O--Si R.sup.1.sub.2R.sup.Alk i-VI
wherein P.sup.i denotes the remainder of the polymer chain which
may incorporate same or different units, and R.sup.1 is as
hereinbefore defined.
[0065] Prepolymer (i) may also comprise a polyorganosiloxane
exhibiting, per molecule, at least two C.sub.2-0.sub.6 alkenyl
groups bonded to the silicon and having, for example, a viscosity
of between 10 and 300 000 mPas, which can in particular be formed
of at least two siloxyl units of formula:
Y d R e Si O ( 4 - d - e ) 2 ( III ) ##EQU00001##
in which: [0066] Y is a C.sub.2-0.sub.6 alkenyl such as vinyl,
allyl or hexenyl groups, preferably vinyl, [0067] R is a monovalent
hydrocarbon group with no unfavorable effect on the activity of the
catalyst which is generally chosen from alkyl groups having from 1
to 8 carbon atoms inclusive, such as the methyl, ethyl, propyl and
3,3,3-trifluoropropyl groups, cycloalkyl groups, such as the
cyclohexyl, cycloheptyl and cyclooctyl groups, and aryl groups,
such as xylyl, tolyl and phenyl, [0068] d is 1 or 2, e is 0, 1 or 2
and d+e=1, 2 or 3, [0069] optionally all the other units being
units of average formula:
[0069] R f Si O 4 - f 2 ( IV ) ##EQU00002## [0070] in which R has
the same meaning as above and f=0, 1, 2 or 3.
[0071] Examples of prepolymer (i) are, for example,
dimethylpolysiloxanes comprising dimethylvinylsilyl ends,
(methylvinyl)(dimethyl)polysiloxane copolymers comprising
trimethylsilyl ends or (methylvinyl)(dimethyl)polysiloxane
copolymers comprising dimethylvinylsilyl ends.
[0072] A convention accepted in the art for denoting the units of
silicones according to the number of oxygen atoms bonded to the
silicon is used here. This convention uses the letters M, D, T and
Q (abbreviations for "mono", "di", "tri" and "quatro") to denote
this number of oxygen atoms. This nomenclature of silicones is
described, for example, in the work by Walter Noll, "Chemistry and
Technology of Silicones", Academic Press, 1968, 2nd edition, on
pages 1 to 9.
[0073] Prepolymer (i) may also be a silicone resin bearing at least
two alkenyl, preferably vinyl groups. Such silicone resin
comprising at least two different siloxane units chosen from those
of M siloxane unit of formula R.sub.3SiO.sub.1/2, D siloxane unit
of formula R.sub.2SiO.sub.2/2, T siloxane unit of formula
RSiO.sub.3/2 and Q siloxane unit of formula SiO.sub.4/2,
[0074] wherein R denotes a monovalent hydrocarbon group, with the
conditions that at least one of these siloxane units being a T or Q
siloxane unit and that at least two of the M, D and T siloxane
units comprises an alkenyl group.
[0075] The silicone resin could be selected from the group
consisting of: [0076] an organopolysiloxane resin of formula
MT.sup.ViQ consisting essentially of: [0077] (a) trivalent siloxane
units T.sup.Vi of the formula R'SiO.sub.3/2; [0078] (b) monovalent
siloxane units M of the formula R.sub.3SiO.sub.1/2, and [0079] (c)
tetravalent siloxane units Q of the formula SiO.sub.4/2 [0080] an
organopolysiloxane resin of formula MD.sup.ViQ consisting
essentially of: [0081] (a) divalent siloxane units D.sup.Vi of the
formula RR'SiO.sub.2/2; [0082] (b) monovalent siloxane units M of
the formula R.sub.3SiO.sub.1/2, and [0083] (c) tetravalent siloxane
units Q of the formula SiO.sub.4/2 [0084] an organopolysiloxane
resin of formula MDD.sup.ViQ consisting essentially of: [0085] (a)
divalent siloxane units D.sup.Vi of the formula RR'SiO.sub.2/2;
[0086] (b) divalent siloxane units D of the formula
R.sub.2SiO.sub.2/2 [0087] (b) monovalent siloxane units M of the
formula R.sub.3SiO.sub.1/2, and [0088] (c) tetravalent siloxane
units Q of the formula SiO.sub.4/2 [0089] an organopolysiloxane
resin of formula M.sup.ViQ consisting essentially of: [0090] (a)
monovalent siloxane units M.sup.Vi of the formula
R'R.sub.2SiO.sub.1/2; and [0091] (b) tetravalent siloxane units Q
of the formula SiO.sub.4/2, and [0092] an organopolysiloxane resin
of formula M.sup.ViT.sup.ViQ consisting essentially of: [0093] (a)
monovalent siloxane units M.sup.Vi of the formula
R'R.sub.2SiO.sub.1/2; [0094] (b) trivalent siloxane units T.sup.Vi
of the formula R'SiO.sub.3/2, and [0095] (c) tetravalent siloxane
units Q of the formula SiO.sub.4/2
[0096] wherein R denotes a monovalent hydrocarbon group such as
methyl and R' denotes a vinyl group:
[0097] Such resins are well-known branched organopolysiloxane
oligomers or polymers which are commercially available. They are
provided in the form of solutions, preferably siloxane
solutions.
[0098] Prepolymer (ii) in-chain and end-capping
polyorganohydrogensiloxane units are preferably selected from the
formula II-I and ii-II:
--O--Si R.sup.2H--O-- ii-I
--O--Si R.sup.2.sub.2H, ii-II
more preferably prepolymer (ii) is selected from formula II-III and
ii-IV:
P.sup.ii-O--Si R.sup.2H--O--P.sup.ii ii-III
P.sup.ii-O--Si R.sup.2.sub.2H ii-IV
wherein
[0099] P.sup.ii denotes the remainder of the polymer chain which
may incorporate same or different units and one or more groups
R.sup.2 are organo groups suitably independently selected from
optionally fluorinated C.sub.1-20 alkyl and cycloalkyl, C.sub.5-20
aryl and combinations thereof, for example from methyl, ethyl,
propyl, butyl, pentyl, hexyl, heptyl, octyl, nonyl and/or decyl
groups.
[0100] Prepolymer (ii) preferably comprises a
polyorganohydrogensiloxane-polydiorganosiloxane copolymer,
incorporating one or more units ii-I and/or ii-II:
--O--Si R.sup.2H--O-- ii-I
--O--Si R.sup.2.sub.2H ii-II
and one or more units ii-V and/or ii-VI:
--O--Si R.sup.2.sub.2--O-- ii-V
--O--Si R.sup.2.sub.3 ii-VI
wherein R.sup.2 is as hereinbefore defined, more preferably
copolymer incorporating polyorganohydrogensiloxane end-capping
units, i.e prepolymer chains terminate with the group or moiety
ii-VII:
.ident.Si--H, ii-VII
more particularly with the unit of formula II-II:
--O--Si R.sup.2.sub.2H ii-II
as hereinbefore defined. Most preferably prepolymer (ii) comprises
methylhydrogensiloxane-dimethylsiloxane copolymers.
[0101] Prepolymer (ii) may also comprises a polyorganosiloxane,
exhibiting, per molecule, at least two hydrogen atoms bonded to the
silicon and preferably at least three ESiH units and having, for
example, a viscosity of between 1 and 5000 mPas, which can in
particular be formed of siloxyl units of formula:
H g X i Si O 4 - g - i 2 ( V ) ##EQU00003##
in which: [0102] X is a monovalent hydrocarbon group with no
unfavorable effect on the activity of the catalyst which is
generally chosen from alkyl groups having from 1 to 8 carbon atoms
inclusive, such as the methyl, ethyl, propyl and
3,3,3-trifluoropropyl groups, cycloalkyl groups, such as the
cyclohexyl, cycloheptyl and cyclooctyl groups, and aryl groups,
such as xylyl, tolyl and phenyl, [0103] g=1 or 2, preferably =1,
i=0, 1 or 2 and g+i=1, 2 or 3, optionally all the other units being
units of average formula:
[0103] X j Si O 4 - j 2 ( VI ) ##EQU00004## [0104] in which X has
the same meaning as above and j=0, 1, 2 or 3.
[0105] Examples of prepolymer (ii) are polymethylhydrosiloxanes or
methylhydrodimethylsiloxane copolymers.
[0106] Alternatively or additionally prepolymers (i) and (ii) are
as defined in U.S. Pat. No. 5,153,231 for Cavi-Care RTV-2 type
compositions, also as defined in US 2006/0217016, U.S. Pat. No.
3,928,629 and U.S. Pat. No. 4,529,553, U.S. Pat. No. 4,714,739 and
US2002/0010299 the contents of which are incorporated herein by
reference, or as commercially available (Rhodorsil RTFoam 3240,
Mepiseal, Silpuran 2111 A/B, Silpuran 2400/18 A/B, and the like
[0107] In the case that prepolymers include other units additional
to iIIII, iIV, iiI and iiII for example, these are suitably not
reactive with the respective prepolymer at ambient temperature or
under sterilising conditions.
[0108] Suitably the ratio of silicon-bonded hydrogen atoms provided
by (ii) to silicon-bonded alkenyl moieties provided by (i) is at
least 0.5:1, preferably 1:1,
[0109] Preferably, embodiments of the curable composition follows
the catalysed addition cure reaction according to the following
scheme:
P.sup.i-R.sup.Alk1--CR.sup.Alk1.dbd.CR.sup.Alk2.sub.2+P.sup.ii--SiHR.sup-
.2R.sup.2/P.fwdarw.[catalyst]
P.sup.i--R.sup.Alk1--CHR.sup.Alk1CR.sup.Alk2.sub.2--SiR.sup.2R.sup.2/PP.-
sup.ii
[0110] more preferably:
##STR00001##
wherein integers are as hereinbefore defined and R.sup.11 selected
from P.sup.i and R.sup.1 as hereinbefore defined and R.sup.2/P is
selected from P.sup.ii and R.sup.2 as hereinbefore defined.
[0111] Suitably the prepolymers (i) and (ii) and catalyst (iii) are
apportioned in at least one Part A and at least one Part B in
manner to provide respective Parts A and B which in isolation are
not reactive at ambient temperature, nor under sterilisation
conditions. Apportioning may also be determined according to volume
and viscosity. The at least one Part A and at least one Part B may
be of substantially equal volume and viscosity or of different
volume and/or viscosity. Part A or Part B may incorporate a
suitable viscosity moderator or diluent, in amount to increase or
reduce volume and/or viscosity. By this means Part A and Part B
having different volume and viscosity may be volume and viscosity
matched for improved ease and intimacy of mixing and dispensing. A
suitable diluent is for example a silicone oil which is available
in any desired viscosity for thickening or thinning effect.
Advantageously we have found that Part A comprising a silicone oil
is radiation sterilisable without deleterious effect on properties
of the resultant cured composition.
[0112] In the case that Part A is of greater volume and higher
viscosity than Part B, Part A may be apportioned between two or
more Parts A1, A2 etc, of equal volume, providing 3 or more Parts A
and B of approximately equal volume. Alternatively or additionally
Part B may incorporate silicone oil as a substantially inert
diluent and/or thickener.
[0113] In a preferred embodiment of the invention Part A
incorporates an amount of (i) one or more polydiorganosiloxane
prepolymers having at least one organoalkylenylsiloxane unit per
molecule, and additionally (iii) a catalyst for curing by addition
of prepolymer (i) organoalkylenylsiloxane to prepolymer (ii)
organosiloxane, and Part B incorporates an amount of (i) one or
more polydiorganosiloxane prepolymers having at least one
organoalkylenylsiloxane unit per molecule, together with (ii) the
one or more polydiorganosiloxane prepolymers having at least one
organohydrogensiloxane unit per molecule. In this case, the volume
and viscosity of Parts A and B may be approximately equal, in known
manner.
[0114] In one composition, Part A incorporating the catalyst (iii)
incorporates substantially only one of prepolymers (i) and (ii),
preferably only prepolymer (i). If present prepolymer (ii) is
present in trace amount insufficient to significantly react and
significantly increase prepolymer viscosity at elevated temperature
prior to mixing and curing. A significant viscosity increase is
greater than 0% up to 5% by weight.
[0115] The Parts A and B are suitably comprised in respective
receptacles in a volume of from 80 to 99.9% of the receptacle
volume, preferably from 90 to 99.9% thereof, more preferably from
95 to 99.9% thereof, most preferably from 98 to 99.9% thereof.
Receptacles may comprise respective one or more composition part or
parts under an inert atmosphere or vacuum. The removal of air or
water present in the receptacle is advantageous. This appears to
minimise degradation as assessed by the appearance of the parts,
after sterilisation.
[0116] A catalyst as hereinbefore defined may be any catalyst which
is effective in catalysing the addition curing reaction as
hereinbefore defined, more preferably as hereinabove illustrated.
Suitable catalysts are selected from any known form of platinum,
rhodium, palladium, nickel and like addition curing hydrosilylation
catalysts, for example as disclosed in U.S. Pat. No. 5,153,231, US
2006/0217016, U.S. Pat. No. 3,928,629 and U.S. Pat. No. 4,529,553
the contents of which are incorporated herein by reference.
[0117] A platinum catalyst may be selected from platinum black,
platinum as deposited on carriers including silica such as silica
gel or carbon such as powdered charcoal, platinic chloride or
chloroplatinic acid and alcohol solutions thereof, salts of
platinic and chloroplatinic acids and platinum complexes such as
platinum/olefin, platinum/alkenylsiloxane, platinum/beta-diketone,
platinum/phosphine and the like. Chloroplatinic acid may be the
hexahydrate or anhydrous form. A platinum complex may be prepared
from chloroplatinic acid and its hexahydrate, or from platinous
chloride, platinum dichloride, platinum tetrachloride and their
neutralised complexes with divinyltetramethyldisiloxane, optionally
diluted with dimethylvinylsiloxy endcapped
polydimethylsiloxane.
[0118] A palladium catalyst may be selected from palladium on
carbon, palladium chloride and the like.
[0119] A rhodium catalyst may be selected from rhodium chloride and
one or more complexes of rhodium having the general formula iii-I
or iii-II:
RhX.sub.3(SR.sub.2).sub.3 (iii-I)
Rh.sub.2(CO).sub.4X.sub.2 (iii-II)
wherein each X represents a halogen atom and each R represents an
alkyl or aryl radical or combination thereof having from 1 to 8
inclusive carbon atoms or the R'.sub.3SiQ group in which Q
represents a divalent aliphatic hydrocarbon radical having from 1
to 6 inclusive carbon atoms and R' represents an alkyl or aryl
radical or combination thereof having from 1 to 8 inclusive carbon
atoms or a (CH.sub.3).sub.3Si-- group, not more than one R' per
molecule being (CH.sub.3).sub.3Si--. For example rhodium
chloride/di(n-butyl)sulfide complex and the like.
[0120] A nickel catalyst is preferably a zero valent nickel
selected from M.sub.2Ni.sup.(0) such as
bis(1,5-cyclo-octadienyl)nickel (Ni(COD).sub.2) and from
MNi.sup.(0)G wherein M is a bidentate alkene cyclic hydrocarbon
ring of C.sub.8-12 and G is selected from monodentate and bidentate
phosphorous groups having hydrogen atoms, substituted or
unsubstituted hydrocarbon radicals or mixtures thereof bonded to
the phosphorous atoms of the phosphorous groups.
[0121] Preferably the composition comprises an addition-reaction
retardant or a crosslinking inhibitor chosen, for example, from the
following compounds: [0122] polyorganosiloxanes substituted with at
least one alkenyl that may optionally be in cyclic form,
tetramethylvinyltetrasiloxane being particularly preferred, [0123]
organic phosphines and phosphites, [0124] unsaturated amides,
[0125] alkyl maleates, and [0126] acetylenic alcohols.
[0127] These acetylenic alcohols (see FR-A-1 528 464 and FR-A-2 372
874), which are among the preferred thermal blockers of the
hydrosilylation reaction, have the formula:
(R')(R'')C(OH)--C.ident.CH
in which formula [0128] R' is a linear or branched alkyl radical,
or a phenyl radical; [0129] R'' is H or a linear or branched alkyl
radical, or a phenyl radical; the radicals R', R'' and the carbon
atom alpha to the triple bond possibly forming a ring; and [0130]
the total number of carbon atoms contained in R' and R'' being at
least 5 and preferably from 9 to 20.
[0131] Examples that may be mentioned include: [0132]
1-ethynyl-1-cyclohexanol; [0133] 3-methyl-1-dodecyn-3-ol; [0134]
3,7,11-trimethyl-1-dodecyn-3-ol; [0135] 1,1-diphenyl-2-propyn-1-ol;
[0136] 3-ethyl-6-ethyl-1-nonyn-3-ol; [0137] 2-methyl-3-butyn-2-ol;
[0138] 3-methyl-1-pentadecyn-3-ol.
[0139] These .alpha.-acetylenic alcohols are commercial products.
Such a retardant is present in a maximum proportion of 3000 ppm
relative to the total weight of the polyorganosiloxanes in the
silicone composition. Methyl butynol could be chosen as in
Cavi-Care.
[0140] The composition may be non-foamable or may be foamable,
comprising (iv) a blowing agent, selected from any agent which
evolves gas or vapour as part of or during the curing reaction, for
example selected from H-donors, OH-containing agents, H-bonding
agents such as: [0141] alcohols including methanol, ethanol,
n-propanol, isopropanol, n-butanol, 2-butanol, tert-butanol,
n-hexanol, n-octanol and benzyl alcohol. n-Propanol, n-butanol,
n-hexanol and n-octanol are particularly preferred, [0142] polyols
such as diols including, 4-butanediol, 1,5-pentanediol and 1,7
heptanediol, [0143] silane or polysilane having at least one
silanol group, or [0144] water.
[0145] A foamable composition may produce a foam having any desired
porosity or pore architecture. In a particular advantage a foamable
composition provides an open-pore foam. A preferred foamable
composition is adapted to deliver a foam of very high free internal
volume, e.g. of the order of 70% to 90%. Preferred porous foams are
of mechanical strength to prevent the foam structure collapsing in
use, more preferably are adapted to form a cured three dimensional
body which is resiliently deformable.
[0146] Preferably a foamable composition is adapted to deliver a
foam which cures to form open interfaces with moist or wet
surfaces. Such open-interface foams are suitable for communicating
with wound surfaces via the foam body, for example. In a particular
advantage we have found that such open-interface foams are provided
by silicone compositions. In a further advantage the composition is
suitable for providing a cured porous three dimensional body of
desired shape.
[0147] The composition may be non-foamable or may be foamable,
comprising (iv) a blowing agent, selected from any agent which
evolves gas or vapour as part of or during the curing reaction, for
example selected from H-donors, OH-containing agents, H-bonding
agents such as: [0148] alcohols including methanol, ethanol,
n-propanol, isopropanol, n-butanol, 2-butanol, tert-butanol,
n-hexanol, n-octanol and benzyl alcohol. n-Propanol, n-butanol,
n-hexanol and n-octanol are particularly preferred, [0149] polyols
such as diols including, 4-butanediol, 1,5-pentanediol and 1,7
heptanediol, [0150] silane or polysilane having at least one
silanol group, or [0151] water.
[0152] The composition may comprise active agents, which may have
any desired activity for the intended purpose, for example
medically active agents and the like. Suitable active agents or
APIs are thermally stable as hereinbefore defined, preferably are
stable under the required thermal cycle to achieve terminal
sterility of the compositions disclosed herein. These are commonly
selected from antimicrobial agents and disinfectants such as silver
and derivatives including silver oxide, silver nitrate, silver
acetate and silver chloride, biguanides including polyhexamethylene
and chlorhexidine glucanate and its acetate salt, active agents
such as pharmaceuticals, biocides, growth factors, hemostats and
the like, nutrients, pain killers and agents to minimise discomfort
and the like and combination materials. Antimicrobial agents,
biocides and disinfectants may be selected from silver, in
particular nano crystalline silver, and derivatives including
silver complexes and salts such as ionic silvers, silver zeolite,
silver oxide, silver nitrate, silver acetate, silver chloride,
silver sulphadiazine), biguanides including polyhexamethylene
biguanide and chlorhexidine digluconate and its acetate salt
chlorhexidine acetate and diacetate, manuka honey, peroxides (e.g.
hydrogen peroxide), iodine (e.g. povidone iodine), sodium
hypochlorite, copper, copper complexes; zinc (e.g. zinc oxide, zinc
pyrithione), gold, gold complexes; phosphates, amines, amides and
sulphonamides (e.g. hexatidine, proflavine. mafenide,
nitrofurazone, norfloxacin; antibiotics (e.g. gentamicin,
bacitracin, rifampicin; alcohols and acids (e.g. ethanol, phenoxy
ethanol, mupirocin); known irradiation stable antimicrobials
include Chlorhexidine acetate, silver sulphadiazine(SSD) and nano
crystalline silver, these are active components of terminally
sterile commercially available products Bactigras.TM., Allevyn
Ag.TM. and Acticoat.TM. respectively; nutrients, pain killers and
other pain management techniques suitably include analgesics and
anasthetics and may be selected from amethocaine, lignocaine,
non-steroidal anti-inflammatory drugs);
[0153] Heamostats may be selected from Chitin, chitosan, kaolin;
Antifibrinolytics such as amino acids, aminocaproic acid,
tranexamic acid, aminomethylbenzoic acid; Proteinase inhibitors
including aprotinin, alfa1 antitrypsin, C1-inhibitor, camostat;
Vitamin K and other hemostatics including vitamin K,
phytomenadione, menadione; Fibrinogen including human fibrinogen;
Local hemostatics including absorbable gelatin sponge, oxidized
cellulose, tetragalacturonic acid hydroxymethylester, adrenalone,
thrombin, collagen, calcium alginate, epinephrine; Blood
coagulation factors including coagulation factor IX, II, VII and X
in combination, coagulation factor VIII, factor VIII inhibitor
bypassing activity, coagulation factor IX, coagulation factor VII,
Von Willebrand factor and coagulation factor VIII in combination,
coagulation factor XIII, eptacog alfa (activated), nonacog alfa,
thrombin. Systemic hemostatics: etamsylate, carbazochrome,
batroxobin, romiplostim, eltrombopag;
combination materials including superabsorbers, Odour management,
Wovens and non wovens, Gellable fibres; Growth factors, Wound
debridements--mechanical, autolytic and enzymatic; Resorbable
dressings and micro structure to influence cell ingrowth; Cells,
tissue (e.g. autologous treatments); Indicators; Dyes and
colourants.
[0154] Preferred compositions may include additional components
selected from adjuvants, preservatives, extenders and the like.
Adjuvants are preferably selected from fillers, colorants, coloured
indicators. Preservatives include propyl gallate.
[0155] Preferably a composition comprises, by weight percent:
Part A:
[0156] one or more prepolymers (i) (80-99%) blowing agent (0-10%) a
catalyst (>0-5%) preservative (0-0.1%)
Part B:
[0157] one or more prepolymers (i) (60-69%) one or more prepolymers
(ii) (29-35%) a foam stabiliser (0-11%) a catalyst inhibitor
(0-0.1%) preservative (0-0.1%) diluent or viscosity modifier
(0-75%).
[0158] Part A:B may be present in a 1:99:99:1, for example 30:70 to
99:1 volume % ratio, respectively with or without added diluent or
viscosity modifier. Preferably Part A:Part B is present in 30:70 to
70:30 volume % ratio, more preferably 45:55 to 55:45, such as
substantially 50:50. Preferably Parts A and B are of compatible
viscosity enabling mixing and substantially complete reaction
thereof. Suitably viscosity of Part A:Part B is in the range
6:1-1:8, preferably 5:1-1:5, more preferably substantially 1:1.
Compositions of disparate viscosity may be mixed in devices with
increased length mixing head for example. The sterilisation of a
composition may induce some viscosity increase, and therefore the
viscosity ratio is preferably that of the Parts
post-sterilisation.
[0159] Preferably the composition comprises prepolymers which are
relatively short in length compared to that of the intended
sterilised prepolymer. Prepolymers undergo chain lengthening during
irradiation to a desired final viscosity or density. Preferably the
Part A prepolymer(s) having at least one alkenyl unit or moity per
molecule are relatively short in length compared to that of the
corresponding sterilised Part A prepolymer(s).
[0160] Preferably the respective sterilised Parts are of a
viscosity suitable for mixing by hand within a period of up to 1
minute. In a particular advantage Part A and/or Part B may comprise
shortened pre-polymers that will increase in molecular weight
during sterilisation to give species with the desired properties
following sterilisation. More particularly Part A and optionally
Part B comprise pre-polymers of chain length determined such that
an increase in molecular weight after irradiation sterilisation
confers on the prepolymers a desired molecular weight, viscosity,
rheology or the like following sterilisation. Most preferably Part
A comprises such shortened pre-polymers. Shortening is preferably
to a percentage corresponding to the percentage increase in
molecular weight and viscosity of the Part during sterilisation.
This percentage will vary according to the chemical nature of any
given composition. For example for a polydiorganosiloxane
composition, shortening of Part A prepolymers is typically to the
extent to give a 9-11% reduction in viscosity and shortening of
Part B prepolymers is typically to the extent to give a 17-23%
reduction in viscosity.
[0161] A problem envisaged with dispensing low viscosity
compositions in the lower part of the range 5-300 Pa*s is retaining
the composition in position at an intended site until cure is
complete. Low viscosity compositions tend to flow within or away
from an intended site during the initial period of cure, if not
contained. WO2004/108175 (Molnlycke Health Care AB) discloses the
compounded problem encountered if the composition is affected by
movements of the body, pressure or friction. Preferably the
composition may have, on initial mixing, a viscosity within the
range 10-120 Pa*s, more preferably within the range 20-80 Pa*s. The
composition may comprise one or more fillers to confer thixotropic
properties thereon. A suitable filler may be fumed silica, for
example such as Wacker Chemie, Wacker HDK.TM. WO2004/108175
discloses Wacker HDK.TM. as especially effective for this
purpose.
[0162] Prepolymers (i) and (ii) have cross-linking function,
prepolymer (ii) may also cooperate with blowing agent to cause
foaming.
[0163] More preferably a composition comprises, by part weight, a
composition as recited in U.S. Pat. No. 5,153,231 example col 7 the
contents of which are incorporated herein by reference, for example
Cavi-Care:
TABLE-US-00001 Parts by Ingredients weight Part A
Dimethylvinylsilyl endblocked PDMS, viscosity 54 450 mm.sup.2/s,
0.01 mol % vinyl groups Dimethylvinylsilyl endblocked PDMS,
viscosity 39 9000 mm.sup.2/s, 0.002 mol % vinyl groups Ethanol 3
Chloroplatinic acid 4 Propyl gallate 0.01 Part B Methyl butynol
0.05 Dimethylvinylsilyl endblocked PDMS, viscosity 10 450
mm.sup.2/s, 0.01 mol % vinyl groups Dimethylvinylsilyl endblocked
PDMS, viscosity 54 9000 mm.sup.2/s, 0.002 mol % vinyl groups
Trimethylsilyl endblocked 16 polymethylhydrogensiloxane, viscosity
30 mm.sup.2/s, 1.5 mol % hydrogen Polymethylhydrogen-PDMS,
viscosity 5 mm.sup.2/s, 16 0.75 mol % hydrogen Foam
stabiliser-hexamethyldisiloxane coated 4 polysilicates treated with
the alcohol F(CF.sub.2).sub.8CH.sub.2CH.sub.2OH Propyl gallate
0.01
[0164] In a further aspect there is provided a method of preparing
a composition as hereinbefore defined from its composition
precursor comprising the steps of:--
combining prepolymers (i), (ii) and catalyst (iii) as hereinbefore
defined to form at least one Part A and at least one Part B as
hereinbefore defined; and sealing the Part(s) A and Part(s) B in
receptacles with barrier means as hereinbefore defined.
[0165] Preferably combining is with additional components, by
weight percent as hereinbefore defined
[0166] In a further aspect there is provided a method for the
preparation of a sterile composition comprising subjecting at least
one of Part A and Part B, provided in or on a thermally stable
receptacle or support as hereinbefore defined to elevated
temperature of 121 C or more for a period of up to 28 hours.
[0167] Sterilization is regarded as a special process because of
the difficulty in verifying by retrospective testing that products
which have been through a sterilisation cycle are in fact sterile.
Sterilisation controls for medical devices are achieved by a
combination of validated sterilisation processes, selection of
packaging appropriate to the sterilisation process and the
application of quality assurance principles to the control of
microbial bioburden on raw materials, intermediates, finished
products and the manufacturing environment. The results are
determined as the "bioburden" this being the population of viable
microorganisms on a product and/or a package. A product is
determined "sterile" if free from viable microorganisms.
[0168] A sterility assurance level (SAL) is given as the
probability of a viable microorganism being present on a product
unit after sterilisation. SAL is normally expressed as 10.sup.-n.
Requirements for terminally sterilized devices to be labelled
"sterile" are defined as a SAL of 10.sup.-6, or in other words that
the theoretical probability of there being a viable microorganism
present on a device is equal to or less than 1.times.10.sup.6 (BS
EN 556--1:2001 Sterilisation of medical devices--Requirements for
terminally sterilised devices to be labelled sterile).
[0169] The sterilisation may be conducted at any combination of
elevated temperature and time which achieves terminal sterility and
which lies within the thermal stability temperature range of the
receptacle(s) or support(s). Higher temperatures increase costs,
but longer time periods can be less well tolerated by receptacles
and supports.
[0170] A suitable sterilisation regime may be determined based on
the following, although variations are possible: [0171] 123.degree.
C.->24 hours--(i) and/or (ii) [0172] 134.degree. C.->6
hours--(i) and/or (ii) [0173] 160.degree. C.-100 minutes--(i)
and/or (ii).
[0174] Preferably a suitable sterilisation regime is selected,
whereby for a desired packaging material, a sterilisation
temperature Td is less than or equal to the thermal instability
threshold temperature of the packaging, eg the Vicat T, less
5.degree. C., or for a given sterilisation temperature Td, a
suitable packaging material has thermal instability threshold
temperature of the packaging, eg the Vicat T, greater than or equal
to Td+5.degree. C. By reading across a suitable chart, a suitable
sterilisation time for the sterilisation temperature can then be
determined. A material whose maximum temperature and time threshold
lies substantially below the thermal instability threshold
temperature is not suitable for use in the invention. For a
material whose values lie above the thermal instability threshold
temperature, possible sterilisation conditions include decreased
time or temperature. Alternatively a suitable sterilisation regime
is selected having regard to Graph 2 hereinabove.
[0175] In a further aspect of the invention there is provided the
medical or non-medical, dental or non-dental use of a composition
or elastomer as hereinbefore defined. Such use includes use as
dyes; preservatives; gels; foams; aerosols; pharmaceuticals;
adhesives; encapsulants; hair/skin care; cosmetic use; dental use;
release coatings; coatings; adhesives and sealants; wound care;
skin care including scar reduction; cavity care; medical device
encapsulation such as electronic device encapsulation for
biomedical applications; mould making; orthopaedics; drug delivery
systems including antimicrobial systems; haemostatic and
pharmaceutical systems; nutrition including manufacture of
foodstuffs; aerospace, marine and submarine applications;
ecologically sensitive applications; confined or isolated
organisms, or their habitats, or confined or isolated medium or
atmosphere such as those having low immunity; sterile, clean or
aseptic applications; germination or propagation of living matter
such as plants or organisms; including manufacture and repair of
equipment, apparatus or components for any of the above and in
particular aerospace, submarine sterile, clean or aseptic,
germination or propagation.
[0176] A medical use of particular advantage is as a foamable
composition as hereinbefore defined. A foamable composition is
particularly suited for use in wound therapy, more particularly for
use as a wound filler or wound packing material or cavity foam
dressing, most particularly in NPWT. The foamable composition is of
particular advantage in that it may be used in a sterile field or
environment. It is in this field, working on very severe wounds,
that the advantages of a dispensable shapable foam are most
relevant, and yet a non-sterile composition can not be used.
Accordingly embodiments disclosed herein enable for the first time
the use of a curable foam composition in a sterile field.
[0177] Embodiments of the foamable composition for use in wound
care or wound therapy may be suitable for providing a porous cured
three dimensional resiliently deformable body. This is of
particular advantage in providing support for the wound whilst
being compressible as the wound heals and closes.
[0178] Preferably the foamable composition provides an open-pore
cured three dimensional body. In the case of a composition suited
for NPWT, the open pore system allows the development of a negative
pressure at the wound, transmitted through the open-pore foamed
body. Wound fluids may be evacuated through the foamed body.
[0179] In foam based NPWT the wound cavity is filled or covered
with a porous foam packing material and covered over and sealed
with flexible sheet (a drape) that is fairly impermeable to fluids.
In gauze based NPWT a corresponding procedure is followed but using
gauze packing material in place of porous foam packing material. In
combination dressing or preformed dressing based NPWT either
procedure may be followed if gauze or foam are to be used. A vacuum
line is inserted under or through the drape into the wound site and
its distal end is connected to a vacuum source (commonly a pump).
The wound cavity, enclosed by the drape and tissue, contracts under
the force of atmospheric pressure and compresses the packing
material visibly. Gross tissue movement ceases after a few tens of
seconds and fluid flow from the wound (withdrawn from the tissue)
ensues. The fluid is transmitted through the packing material and
up the vacuum line to a collection receptacle positioned between
the distal end of the vacuum line and the vacuum source. The wound
packing material mechanically supports the tissue to which it is
applied, and also allows the free flow of fluids away from the site
when a vacuum is applied, even when compressed.
[0180] Porosity is a function of number of pores and their size. It
can be conveniently measured as a function of volume increase. The
foamable composition suitably delivers a foam having a volume
increase compared to the composition in the range from 3 to 10.
Volume increase may be regulated by choice and amount of foaming
agent, but is also a function of the polymer. In a particular
advantage certain polydiorganosiloxane compositions may deliver
porosity which is eminently suitable for wound care applications.
Preferably, the body is of very high free internal volume, e.g. 70%
to 90%.
[0181] Generally, the size of the pores affects the transmission of
negative pressure. Therefore, the smaller the pores, the smaller
the negative pressure which can be established and the shorter its
duration as the foam is progressively compressed by surrounding
tissue growth. However the larger the pore size the lower the
tensile strength, and the lower the support which the foam is able
to deliver.
[0182] In a preferred embodiment the pores are resilient to tissue
contraction, and do not collapse under contraction, whereby
negative pressure may be maintained. The composition suitably
delivers a foamed cured material having resilience and tensile
strength capable of withstanding negative pressure of more than
-150 mmHg, preferably 60-120 mmHg such as 60-100 mmHg below ambient
atmospheric pressure, or 80-120 mmHg below ambient atmospheric
pressure without causing the foam to collapse.
[0183] Preferably a foamable composition is adapted to deliver a
foam which is open at its interfaces with moist or wet surfaces,
more preferably is a silicone composition. This creates the ideal
material for generating a negative pressure at a wound surface
whilst maintaining open communication with the wound itself. In a
further advantage the composition is suitable for providing a cured
porous three dimensional body of desired shape.
[0184] The polydiorganosiloxane composition is adapted to deliver
negative pressure selectively to moist wound surfaces, for example
via an aperture or valve which can be readily inserted directly at
its sealed face remote from the wound surface or indirectly via a
vacuum connection line connecting to such sealed face.
[0185] It will be appreciated that throughout this specification
reference is often made to a wound. In this sense it is to be
understood that the term wound is to be broadly construed and
encompasses open and closed wounds in which skin is torn, cut or
punctured or where trauma causes a contusion. A wound is thus
broadly defined as any damaged region of tissue where fluid may or
may not be produced. Examples of such wounds include, but are not
limited to, incisions, lacerations, abrasions, contusions, burns,
diabetic ulcers, pressure ulcers, stoma, surgical wounds, trauma
and venous ulcers or the like. Certain embodiments of the present
invention are not restricted to use with wounds as will be
discussed in more detail hereinbelow. Use as a wound filling
material, preferably a negative pressure wound therapy wound
filling material as hereinbefore defined includes use on wounds
selected from chronic, acute, traumatic, sub-acute and dehisced
wounds, ulcers (such as pressure or diabetic), partial-thickness
burns and flaps and grafts. These include open, moist, granulating
wounds, preferably surgical wounds such as those resulting from
excision of ulcers, cancerous tissue such as perianal and perineal
wounds and the like. For optimum healing of such wounds, the wound
should be prevented from closing in on itself and allowing fluids
to accumulate, whilst at the same time allowing the tissue around
the wound to progressively contract, and the wound to shrink. Wound
filling materials in NPWT therefore function as a type of "stent",
supporting the wound and holding it open.
[0186] Further medical or non medical uses for which the
composition is particularly advantageous include use as an adhesive
or sealant composition as hereinbefore defined. An adhesive or
sealant composition is particularly suited for use in clean,
aseptic or sterile applications, more particularly as an adhesive
or sealant for clean aseptic storage or packaging of items such as
medicaments, particularly packaging medicaments within a medical
device, or nutritional items and the like, or in the repair and/or
maintenance and/or manufacture of sterile, aseptic or clean devices
or machinery.
[0187] Preferably the composition for use as an adhesive or sealant
in sterile, clean or aseptic conditions is packaged within further
barrier means as hereinbefore defined. Further barrier means
provide a barrier to infection. The composition is therefore a
double wrapped item, this allows for the removal of the first layer
of sterile sealed packaging to reveal receptacles or supports such
as cartridges for or incorporated in a syringe, adhesive strips and
the like, which are completely sterile inside and out, facilitating
entry into a sterile environment. The composition omitting a
further barrier means would comprise a non-sterile external surface
of receptacles or supports and associated barrier means. As it is
not possible to sterilise the composition using standard conditions
for medical apparatus as hereinbefore described, it would not be
possible to take such a composition into a sterile field.
[0188] The adhesive or sealant composition is suitable for
introducing into a clean or aseptic area and dispensing or
releasing into contact with an item to be adhered or sealed.
Optionally a closure means is applied thereto. For example a bead
of sealant may be dispensed around the rim of a sterile bottle
prior to application of a closure means, or to any surface which it
is desired to seal. A closure means or other opposing or adjacent
surface is suitably applied with application of light pressure
thereby ensuring that a seal is produced between the rim and the
lid or other opposing or adjacent surfaces. In this way a universal
sterile sealant is made available to the surgeon or clinician, lab
technician, food manufacturer or mechanic.
[0189] The sealant may be provided in a bagged dual syringe
applicator and dispensed though a static mixer at the point of use.
In this way a sterile dispenser and sealant may be conveniently
provided for the user.
[0190] Certain sealant composition may be useful for example in
sealing medical dressings, is useful for example in restraining
egress of wound exudate or ingress of infection, or providing a
vacuum seal for NPWT application; or as an insitu sterile lid
sealant for laboratory vials and other vessels (e.g. Petri dish
lids, sample storage pots, bijou bottles, culture bottles,
demijohns and dewars) under clean or aseptic techniques; or in the
aseptic manufacture of packaged nutritional items such as for
example foodstuffs including milk, fruit juice, egg; or in the
repair and/or maintenance and/or manufacture of sterile, aseptic or
clean devices or machinery and the like.
[0191] A sealant for medical dressings may be applied in any known
or novel manner. WO 00/74738 (Guyuron) discloses use of silicone
based RTV-2 compositions to seal wounds i.a to minimise potential
infections. The sealant of the invention may suitably therefore be
used by casting on top of the wound and surrounding skin and
allowing to cure.
[0192] WO2004/108175 (Molnlycke Health Care AB) discloses use of
silicone based RTV-2 compositions to disintegrating skin or skin
around wounds i.a to minimise potential infections and protect
against harmful effects of wound exudate. The sealant is used by
applying to skin about a wound, or to disintegrating skin, applying
an adhesive or non-adhesive dressing over the wound and in contact
with the sealant and allowing to cure, or by applying to an
adhesive or non-adhesive dressing, applying the dressing to a wound
and allowing to cure. In either case the dressing is sealed to the
skin about the wound. The composition presents an admirable
improvement on these methods by providing the surgeon, clinician or
patient with a sterile sealant for use in these known manners or
modifications thereof.
[0193] Foodstuffs may be sealed within a container e.g. Tetra Pak
as hereinbefore described. In this way the sealant may be provided
in bulk for industrial scale automated mixing and dispensing (e.g.
using robotic dispensing systems as supplied by Rampf Dosiertechnik
GMBH) in aseptic conditions. Sterile bagged cartridges of the 2
components may be manufactured for insertion in the dispensing
machine. In this way sterile cartridges of the 2 components may be
provided for delivery into the aseptic manufacturing area and
insertion into the dispensing machine.
[0194] In the repair and/or maintenance of machinery, particularly
envisioned is the replacement of gaskets. Here the sealant may be
applied to a flange area or sealing surface as a bead prior to the
bringing together of the components to form a seal. This reduces
the need to sterilise individual gaskets prior to introduction to
the aseptic environment and may reduce the need for multiple
gaskets to be purchased or manufactured. In the aseptic manufacture
of devices or machinery, particularly envisioned is the manufacture
of space craft, marine or submarine craft, or components thereof in
order to meet planetary protection requirements. Here the sealant
composition may be dispensed to create an insitu gasket as
hereinbefore defined. Alternatively the foamable composition may be
dispensed as anti vibration material or insulation for heat or
electrical purposes. The sealant may be provided in a bagged dual
syringe applicator and dispensed though a static mixer at the point
of use. In this way a sterile dispenser and sealant may be
conveniently provided for the user. Alternatively sterile bagged
receptacles such as cartridges of the composition Parts may be
provided for delivery into an aseptic manufacturing area and
insertion into a dispensing machine.
[0195] In a further aspect there is provided a wound dressing
comprising the foamable or foamed composition, adhesive or sealant
or composition thereof as hereinbefore defined.
[0196] In a further aspect of the invention there is provided a
method for dispensing or releasing, and curing a composition as
hereinbefore defined, comprising dispensing into a desired location
or aperture at curing temperature for curing time.
[0197] The composition may be manually mixed and dispensed.
Alternatively any form of dispensing device may be employed.
[0198] In a further aspect of the invention there is therefore
provided a composition dispensing device comprising a terminally
sterile composition as hereinbefore defined. Preferably the device
is a NPWT device. Suitably a device comprises a mixing head having
means to receive 2 or more cartridges comprising Parts A and B.
Cartridges are adapted to locate and lock in place in the device. A
suitable device for NPWT is a double barrelled syringe suitable for
loading with 40 g of pre-polymers and fitted with a mixing
head.
[0199] In a further aspect of the invention there is provided a
method of therapy comprising dispensing a sterile composition as
hereinbefore defined, preferably terminally sterile, to the site of
a wound in a sterile environment.
[0200] In a further aspect of the invention there is provided a
method of therapy as hereinbefore defined which is a method of
negative pressure wound therapy comprising dispensing a terminally
sterile composition as hereinbefore defined directly or indirectly
into a wound and allowing to foam and cure, sealing the wound
including the foamed cured composition and optionally including a
negative pressure connection means, and applying negative pressure
to the wound.
[0201] The composition may be dispensed directly into an open wound
cavity and covered or dispensed into a covered cavity via an
aperture in the cover or dispensed into a mould and inserted into a
wound cavity. An open-pore surface or recess of surface is
generated which may be connected directly or indirectly to a
negative pressure source.
[0202] Currently available wound fillers require removal and
cleansing or changing on a regular basis, typically every 8, 12 or
24 hours, with the maximum recommended period for a dressing to
remain in place being 48 hours in the case for example of foam,
although up to 72 hours for black foam, and 72 hours in the case of
gauze. After longer periods tissue in-growth may occur. In the case
of foam the washed dressing may be reused for up to a week, but as
wound healing progresses successively smaller fillers should be
produced.
[0203] Preferably, the composition may be dispensed into a prepared
wound in a sterile field and may remain in situ without the need to
cleanse and replace because the shaping process is simplified and
highly accurate, rather the used filler is discarded and a new
filler is simply dipensed. The degree of tissue contraction which
has taken place may be determined by monitoring a reduction in the
negative pressure being delivered or by a decrease in the resilient
deformation of the cured composition, and if sufficient contraction
is observed, the cured composition may be removed and new
composition dispensed into the wound for continued therapy. The
foamable curable composition preferably has a pore structure which
is capable of being compressed under moderate pressures, as tissue
contracts, without pore collapse.
[0204] In a further aspect of the invention there is provided a
method for treating a wound site comprising [0205] dispensing a
terminally sterile foamable composition into at least a portion of
the wound site, wherein the foamable composition forms a porous
foam material that is capable of transmitting negative pressure;
[0206] sealing the wound site with a substantially fluid-tight
seal; and applying negative pressure to the wound site using a
source of negative pressure connected to the wound site. Preferably
the foamable composition comprises a first part and a second part.
Preferably the method further comprises curing the composition
prior to sealing the wound site.
[0207] Sealing may be performed after or prior to dispensing the
terminally sterile foamable composition.
[0208] The method may comprise mixing the first and second parts of
the terminally sterile foamable composition together prior to
dispensing or the first and second parts may be mixed while being
dispensed. Preferably the step of connecting a source of negative
pressure to the wound site comprises connecting a conduit to the
wound site through or under the fluid-tight seal. Preferably
sealing the wound site comprises applying a fluid-tight drape over
the wound site. Preferably the terminally sterile foamable
composition is sterilized prior to dispensing by heating the first
and second parts in a thermally stable receptacle or support at an
elevated temperature in excess of 121 C for a period of up to 28
hours.
[0209] Preferably the terminally sterile foamable composition is a
composition as hereinbefore defined.
[0210] Within this aspect of the invention there is provided a
method for treating a wound site, comprising: [0211] dispensing a
terminally sterile composition around at least a portion of the
wound site, wherein the composition comprises a sealant capable of
making a substantially fluid-tight seal; [0212] covering the wound
site with a substantially fluid-tight drape, the drape contacting
at least a portion of the dispensed terminally sterile composition
and forming a fluid-tight seal over the wound; and applying
negative pressure to the wound site using a source of negative
pressure connected to the wound site.
[0213] Preferably the composition comprises a first part and a
second part. Preferably the method further comprises curing the
composition during or after covering the wound site.
[0214] Preferably the method further comprises placing a filler
such as foam, gauze or the like into the wound site.
[0215] The drape suitably comprises an aperture so as to connect
the source of negative pressure. The aperture may be positioned
centrally, to one side or at the perimeter of the drape. The method
may further comprise creating at least one aperture into or under
the drape so as to connect the source of negative pressure.
[0216] Preferably the terminally sterile composition is sterilized
prior to dispensing by heating the first and second parts in a
thermally stable receptacle or support at an elevated temperature
in excess of 121 C for a period of up to 28 hours.
[0217] Preferably the terminally sterile foamable composition is a
composition as hereinbefore defined.
[0218] Within this aspect of the invention there is provided a
further method for treating a wound site, comprising: [0219]
applying a dressing to a wound site [0220] releasing a first part
of a terminally sterile composition from a support around at least
a portion of the wound site and exposing the said part, [0221]
exposing a second part of a terminally sterile composition
supported on a fluid-tight drape [0222] covering the wound site
with the drape, thereby contacting and adhering the exposed first
and second parts and adhering the drape around the wound site; and
applying negative pressure to the wound site using a source of
negative pressure connected to the wound site. Further features of
this method correspond to those described hereinabove.
[0223] It is envisaged that the negative pressure range for certain
embodiments of the present invention may be between about -20 mmHg
and -200 mmHg (note that these pressures are relative to normal
ambient atmospheric pressure thus, -200 mmHg would be about 560
mmHg in practical terms). Aptly the pressure range may be between
about -40 mmHg and -150 mmHg. Alternatively a pressure range of up
to -75 mmHg, up to -80 mmHg or over -80 mmHg can be used. Also
aptly a pressure range of below -75 mmHg could be used.
Alternatively a pressure range of over -100 mmHg could be used or
over -150 mmHg.
[0224] It will be appreciated that according to certain embodiments
of the present invention the pressure provided may be modulated
over a period of time according to one or more desired and
predefined pressure profiles. For example such a profile may
include modulating the negative pressure between two predetermined
negative pressures P1 and P2 such that pressure is held
substantially constant at P1 for a pre-determined time period T1
and then adjusted by suitable means such as varying pump work or
restricting fluid flow or the like, to a new predetermined pressure
P2 where the pressure may be held substantially constant for a
further predetermined time period T2. Two, three or four or more
predetermined pressure values and respective time periods may be
optionally utilised. Aptly more complex amplitude/frequency wave
forms of pressure flow profiles may also be provided eg sinusoidal,
sore tooth, systolic-diastolic or the like etc.
[0225] In a further aspect of the invention there is provided a
wound dressing comprising the foamed composition as hereinbefore
defined. Preferably the wound dressing is a NPWT wound
dressing.
[0226] In a further aspect of the invention there is provided a
NPWT kit comprising a fluid-tight wound dressing, a dispensible or
releasable terminally sterile curable composition and attachment
means for a vacuum pump to supply a negative pressure to the
dressing. Preferably the terminally sterile curable composition is
a composition of the invention as hereinefore defined.
[0227] Embodiments of the invention will now be illustrated in non
limiting manner with reference to the Figures in which
[0228] FIGS. 1 and 2 illustrate a NPWT foam filler wound
dressing;
[0229] FIGS. 3 and 7, 8, 9 and 10 illustrate the use and
application of a dispensable sterile foam filler wound dressing
onto a patient;
[0230] FIGS. 4, 5 and 6 illustrate the a kit including a sealant
composition and wound dressing;
[0231] FIGS. 11 to 15 illustrate the use and application of an
embodiment of a wound cover kit, apparatus and sealant onto a
patient.
[0232] Referring now to FIG. 1, in conventional foam based NPWT the
wound cavity (1) is filled or covered with a porous foam packing
material (2), that may need to be cut to shape (2x shown as 2a) and
covered over and sealed with an adhesive flexible sheet (a drape,
3) that is fairly impermeable to fluids.
[0233] Referring to FIG. 2, a vacuum line (4) is inserted (5) under
or through the drape (3) into the wound site (1), in various
embodiments this is received in a aperture or groove in the foam
(6), or wrapped in gauze. The distal end (not shown) of vacuum line
(4) is connected to a vacuum source (commonly a pump, not shown).
The wound cavity, enclosed by the drape and tissue, contracts under
the force of atmospheric pressure and compresses the packing
material or dressing visibly. The system is however prone to vacuum
leakage.
[0234] In FIG. 3A, a sterile foamable composition is shown (10)
being dispensed from syringe (11) into wound site (1). In FIG. 3B,
the composition cures once dispensed to form a foamed block (12)
contacting the wound bed (1). In FIG. 3C, a drape (3) is placed
thereover and sealed in place in conventional manner. Vacuum line
(4) is inserted (5) through the drape (3) in conventional manner
whereupon vacuum may be initiated via vacuum line (4). The wound
cavity behaves in corresponding manner as described in relation to
FIG. 2. This system improves the fit of the foam filler, and
reduces the stresses placed on the adhesive sealing drape.
[0235] FIG. 4A illustrates a composition for use as a NPWT sealant.
The sealant (20) is used by applying to skin about or around a
wound site (1), or to disintegrating skin. Adhesive or non-adhesive
drape (3) is applied, with optional dressing (not shown) over the
wound (1) and in contact with the sealant (20) and the sealant is
allowed to cure in contact with the drape. Vacuum line (4) is
inserted through an aperture (5) in the drape (3) in conventional
manner whereupon vacuum may be initiated via vacuum line (4). The
sealant improves the quality of the negative pressure transmitted
to the wound bed. FIG. 5 shows a variant of FIG. 4, in which the
pump (8) is removably connected (5a) through aperture (5b) in the
drape (3).
[0236] FIG. 6 shows a further variant in which preformed drape (33
incorporating integral vacuum line sheath (34) and aperture (5) is
positioned over sealant (30) applied via syringe (11). In this case
the drape (33) incorporates an adhesive backing (39), and sealant
is therefore either dispensed about the wound in conventional
manner as shown in step 3, or sealant (33) is dispensed to the
edges of the adhered drape (33) as shown in step 4.
[0237] FIGS. 7 to 10 show a further variant to FIGS. 3A to 3C, in
which the drape (3) is placed over the wound site (1) before
composition (10) is dispensed from syringe (11) through aperture
(5). The composition foams and cures to form a foamed block (12)
including button (13) projecting through aperture (5). Button (13)
is broken off to provide an aperture into the foam body. FIG. 10
shows vacuum line (4) coupled to aperture (5) and connected to
vacuum pump (8) in conventional manner.
[0238] FIGS. 11 to 15 show variants to FIGS. 4a, 5 and 6, relating
to dispensing sealant 20 to seal combination dressings/drapes (2a,
3) including integral port (5) for vacuum line (4). For these
combination dressings (2a, 3) it is necessary to dispense the
sealant (20) to the region of skin (1a) which will underly the
perimeter portion of the drape (3) surrounding the dressing portion
(2a), as shown in FIG. 15. In the case that it is difficult to
prejudge where this perimeter portion will contact the skin (1a),
dispensing about the edge of the combination dressing (2a, 3) is
advantageous, as in FIGS. 11 and 12. Alternatively sealant (20) may
be dispensed at the edge of the drape at positions where leakages
can be observed or are suspected. Alternatively sealant (20) may be
dispensed directly to the combination dressing, also illustrated in
FIG. 15, as a gasket (2), and the dressing then applied over the
wound. In all cases, adhesive tape strips (3a) can be overlaid to
ensure both adhesion and seal are satisfactory. In all cases,
curing, sealing and operation of the vacuum are as previously
described.
[0239] The invention may be carried into practice in various ways,
and embodiments thereof will now be described by way of example
only.
Comparative Example
Example CE1
Preparation of Composition
[0240] RTV-2 polydimethylsiloxane composition Cavi-Care is a
commercially available (Smith & Nephew, Catalogue number 4563)
RTV-2 Pt catalysed foamable silicone elastomer having 30-105
seconds rise time, packaged as Parts A and B in a double foil
laminate sachet laminated to either face with a PE, folded along
the longitudinal axis, both parts of the sachet having a dispensing
nozzle and a common tear notch in the folded edge. Part A contains
predominantly two vinyl functionalised polydimethylsiloxanes and a
platinum based catalyst. Part B contains predominantly vinyl
functionalised polydimethylsiloxanes and a silicone based cross
linking system. Both mixtures are clear to hazy moderately viscous
liquids with a fill weight of 10.0-11.5 g. When mixed together the
two chemical mixtures react to form a soft white, non absorbent
foam dressing.
[0241] The sachet itself is made up of a laminate, used for the
back and front, with a nominal thickness between 100 and 200
micron. It comprises 4 layers:
TABLE-US-00002 PETP (polyethylene terephthalate) 12 .mu.m ALU
(aluminium) 9 .mu.m OPA (biaxially oriented polymide) 15 .mu.m
LLDPE (linear low density polyethylene) 75 .mu.m
Sterilisation--in an Oven
[0242] A Memmert oven was allowed to thermally equilibrate at the
desired temperature (90.degree. C., 100.degree. C., 110.degree. C.,
120.degree. C., 121.degree. C., 123.degree. C., 125.degree. C.,
127.degree. C., 130.degree. C., 136.degree. C.). In each case a
virgin pack of Cavi-Care was placed in the oven for 30 minutes
(121.degree. C. and 136.degree. C. for 15 minutes), autoclaved
using a liquid cycle, removed and the packaging integrity
assessed.
[0243] After sterilisation the following were determined and
compared with unsterilised polymer:
Subjective Assessment of Pack Integrity
[0244] A seal failure was observed when more than 2 crimps were
separated when tested with the package tester.
121.degree. C./15 min: Packaging severely rippled and creased on
the surface; 136.degree. C./15 min: Packaging soft and packaging
heat seal failed; 90.degree. C. and 100.degree. C./30 minutes:
packaging integrity maintained; 110.degree. C./30 min: Part A
inflated; 120.degree. C./30 min: Packaging soft but no silicone
leakage; 121.degree. C./30 min: Packaging soft--seals delaminated
in parts; 123.degree. C./30 min: Packaging soft--seals delaminated
in parts; 125.degree. C./30 min: Packaging soft--possible seals
failure at top of pack; 127.degree. C./30 min: Packaging
failed--small amount of silicone leakage; 130.degree. C./30 min:
Packaging failed--catastrophic seal failure with loss of
containment of the silicones from both Part A and Part B.
[0245] The above investigations yielded the following:
At 127.degree. C. the packaging demonstrated catastrophic failure,
the prepolymer leaking out of the packaging; At 110.degree. C. the
Part A packaging inflates, volatiles have been vaporised and put
stress on the packaging allowing the possibility of
contamination.
[0246] The Vicat softening temperature for typical low density
poly(ethylenes) is reported as 88-100.degree. C. (S. L Aggarwal,
Polymer Handbook, ed. J. Brandrup and E. H. Immergut, Wiley
Interscience, 2.sup.nd edn., 1975, ch. V, pp 20-21.) with optical
melting points for a series of selected poly(ethylenes) spanning
the range 104.2.degree. C. to 135.8.degree. C.
[0247] The existing Cavi-Care packaging is therefore not suitable
for use in an assessment where it will be subject to temperatures
and cycle hold times in the range of 134.degree. C. for 6 hours
through to 123.degree. C. for 24 hours as determined in the
following examples.
Sterilisation--in an Autoclave
[0248] Cavi-Care was autoclaved using a liquid cycle (121.degree.
C. and 136.degree. C. for 15 minutes).
[0249] 121.degree. C. After autoclaving at 121.degree. C. for 15
minutes the packaging was severely rippled and creased on the
surface.
[0250] After autoclaving at 136.degree. C. for 15 minutes the
packaging was soft and the packaging heat seals had failed.
Brookfield Viscosity
[0251] The effect of autoclaving on Cavi-Care prepolymer viscosity
showed no substantial change.
Curing
[0252] The foam density and compressibility was evaluated with foam
made by hand mixing parts A and B together using the spatulas and
pots supplied with each Cavi-Care pack.
Foam Density and Compressibility
[0253] The effect of autoclaving on Cavi-Care cured foam density
showed no change.
Sterility
[0254] Sterility was not investigated for Cavi-Care as the
packaging disintegrated and this was therefore not a viable
product--this type of sterilisation is not appropriate for a liquid
non-aqueous system. If using heat for sterilisation, then a dry
heat at 160 C can be used to properly sterilise the prepolymers.
This type of sterilisation will be challenging for any packaging
that is used.
Example 1
Thermally Stable Composition
Preparation of Composition
Example 1.1
[0255] Cavi-Care (see Comparative Example CE1 above) was repackaged
by filling in sealed vials under argon, glass borosilicate vials
and PP lid (stable to 140.degree. C.) (Fischer Scientific, supplied
by Schott-Duran, catalogue no. BTF-682-030H).
Example 1.2
[0256] Rhodorsil RTFoam 3240 A/B (Bluestar Silicones) is a RTV-2 Pt
catalysed foamable polydimethylsiloxane elastomer having 7.5
minutes rise time. This was packaged by filling in sealed vials
under argon, glass borosilicate vials and PP lid (stable to
140.degree. C.) (Fischer Scientific, supplied by Schott-Duran,
catalogue no. BTF-682-030H).
Example 1.3
[0257] Rhodorsil NPWT was made by reformulating 1.2 to deliver
faster rise time and cure, and foam properties differing in
delivering lower volume, reduced density and increased tensile
strength, although similar pore architecture. This was packaged by
filling in sealed vials under argon, glass borosilicate vials and
PP lid (stable to 140.degree. C.) (Fischer Scientific, supplied by
Schott-Duran, catalogue no. BTF-682-030H).
Sterilisation
[0258] As the Example 1 compositions do not contain a substantial
amount of water, dry heat sterilisation conditions were examined.
Time was allowed for chamber and samples to reach the target
temperature before recording hold time. The hold time was therefore
the time elapsed with contents at the target temperature.
[0259] The composition Example 1.2 was heated in an oven using a
dry heat cycle at:
S1a--121.degree. C. for 1 hour; S1b--160.degree. C. for 100.5
minutes;
[0260] As this regime reduces the number of packaging options
available significantly lower temperatures were sought for the
Example 1.2 composition:
S2--134.degree. C. for 2.5 hours;
[0261] Example 1.3, Rhodorsil NPWT, was heated in an oven using a
dry heat cycle at:
S3--134.degree. C. for 6 hours. S4--123.degree. C. for 24 hours
performed with inspection at 6 hour intervals
[0262] The following were determined and compared with unsterilised
polymer:
Subjective Assessment of Pack Integrity
[0263] Packaging was intact and substantially unaffected by the
sterilisation regime. No visible thermal damage or degradation.
Brookfield Viscosity
[0264] In all cases, parts A and B were of same or comparable
viscosity.
Curing
[0265] After sterilisation each part was then mixed and foamed with
a non-sterilised corresponding part and resultant foam properties
observed.
Foam Density and Compressibility
[0266] The foam densities and compressibilities were evaluated with
foam made by hand mixing parts A and B together using spatulas and
pots supplied with each Cavi-Care pack.
[0267] Foam properties and rise time were same or comparable to
unsterilised foam.
[0268] Example 1.3 Part A foamed with sterilised Part B and part B
foamed with sterilised Part A each delivered foams with rise time
of 2 to 3.25 minutes and substantially unaltered volume (a
reduction of 8 to 10%).
Sterility Testing
[0269] The methodology employed was as follows:
D-value determination: Bacillus atrophaerus biological indicator
(BI) wires (spore wires inoculated with Bacillus atrophaerus ATCC
9372, manufactured by Raven Labs, labelled population
3.4.times.10.sup.6 cfu/wire, labelled dry heat d-value at
160.degree. C. is 1.4 minutes) were used. Biological indicator
population was verified. Biological indicator D-value was verified.
Composition to be tested was placed into respective capillaries,
corresponding to the components to be packaged into respective
receptacles as hereinbefore defined. Each capillary received a BI
wire and was heat sealed thereby being made airtight. Population
and D-value of capillaries was determined based on Raven method
LW1-3100 Revision 3 for metal carriers (disinfect capillary outer
surface, expose wire (Tween 80/glass beads), vortex, refrigerate,
vortex, sonicate, dilute, heat-shock, cool, serial dilute, culture
(Difco TSA/TSB, agar) and incubate, read at 24 hr, 48 hr (also 72
hr for thermally challenged spores) average the 48 hr counts and
use to calculate the mean number of spores per BI). Log reduction
was assessed based on population results from pre and post
exposure.
Sterility
[0270] Sterility testing methodology described above was employed.
The results were as follows:
Population Determination Per Capillary: 1.2A and 1.2B Pre and Post
Exposure (Log Reduction); nnr (Number of Negative Replicates after
7 Days Incubation)
TABLE-US-00003 S1a/ S1b/ Pre/ .times.10.sup.6 cfu .times.10.sup.6
cfu S2/ Capillary .times.10.sup.6 cfu (lr) (lr) nnr Control BI's
12.665 16.200 (6.4036) 4/10 1.2A 9.6676 8.9400 (6.2863) 0/10 1.2B
9.5276 7.9800 (6.2863) 3/10 Lr = log reduction Nnr = number of
negative replicates after 7 days incubation
Population Determination Per Capillary: 1.3A and 1.3B Pre and Post
Exposure (Log Reduction); nnr (Number of Negative Replicates after
7 Days Incubation)
TABLE-US-00004 Pre/.times.10.sup.6 S3/ S4/Nnr S4/Nnr S4/Nnr S4/Nnr
Capillary cfu nnr (6 hrs) (12 hrs) (18 hrs) (24 hrs) Control 25.800
10/10 10/10 BI's 1.3A 1.1025 10/10 0/5 0/5 2/5 5/5 1.3B 9.8875
10/10 2/5 4/5 5/5 5/5 S1a - total survival (variation in counts
withiin error margin); S1b - "total kill" (at least 6 log
reduction) - effective sterilisation; S2 - zero/partial kill (A, B
and controls); S3 - "total kill" (at least 6 log reduction); S4 -
"total kill" (at least 6 log reduction) at 24 hours (Parts A and B)
"total kill" (at least 6 log reduction) at 18 hours (Part B)
fractional kill at 18 hours (Part A) fractional kill at 12 hours
(Part B) total survival at 12 hours (Part A) fractional kill at 6
hours (Part B) total survival at 6 hours (Part A)
Discussion
[0271] As can be seen clearly from the above, compositions 1.2 and
1.3 exposed to 134.degree. C. for 6 hours (S3), 123.degree. C. for
24 hours (S4) and 160.degree. C. for 100.5 minutes (S1b) exhibited
"total kill" (=6 log reduction) in comparison to their counterparts
autoclaved at 134.degree. C. for 2.5 hours (S2) and 121.degree. C.
for 1 hour (S1a).
Example 2
Thermally Stable Composition in Presence of Soft Packaging
[0272] Composition 1.3 was provided in a number of samples
according to Example 1. Vials were contaminated each with a disc or
ring of soft polymeric packaging materials found in tubing,
stoppers, seals and the like, and subject to the heating regime
according to Example 1S3. Control vials uncontaminated were also
subject to the S3 regime.
[0273] Subjective visual assessment and foaming investigation were
conducted (Part A foamed with contaminated Part B, Part B foamed
with contaminated Part A and contaminated Parts A and B
foamed).
[0274] Of the 9 materials investigated:
contamination of vials by 3 translucent materials gave visually
unchanged samples closely matching the rise time and rise volume
profile of uncontaminated samples: Colourless: cured Elastosil LR
3003/50 (Wacker), cured Silpuran 6600/50 (Wacker), White: cured
Thermolast MT Series TM5MED (Kraiburg TPE); contamination of vials
by 2 translucent white materials gave visually unchanged samples
deviating slightly from the rise time and rise volume profile of
uncontaminated samples: cured Thermolast MT/LF Series TM5 LFT
(Kraiburg TPE) and Saint-Gobain Peroxide Silicone Tubing
(Saint-Gobain); contamination of vials by 4 dark grey or black
colored materials gave visually discolored darkened samples each of
which either suffered an 11% to 30% increase in rise volume profile
compared to uncontaminated samples, or suffered a 20 to 30 second
increase in rise time: cured FM480 (Helvoet Pharma), cured FM257
(Helvoet Pharma), BSCF plunger stoppers (BD), NSCF plunger stoppers
(BD)
[0275] Certain silicone rubber, peroxide silicone and styrene block
copolymer materials are suitable as soft packaging materials for
the compositions and methods disclosed herein, subject to
individual testing as in Example 2
[0276] Certain bromobutyl and butadiene containing materials are
considered unsuitable as soft packaging materials for compositions
and methods disclosed herein, subject to individual testing as in
Example 2.
COMPARATIVE EXAMPLE
Example CE2
Thermally Unstable Composition in Presence of Hard Packaging (Lids)
and Enclosed Atmosphere
[0277] Compositions 1.1 and 1.3 were provided in a number of
samples according to Example 1. Borosilicate glass vials were
sealed with a number of lids as shown in Table 3:
temperature resistant lid fitted with PTFE coated silicone
seal--1.3 a) air headspace b) argon purge and headspace Aluminium
screw cap lid with black rubber seal Polypropylene "wadless"
lid.
[0278] Samples were subject to thermal cycle S4 as hereinbefore
defined or of 130.degree. C. for 24 hours (S5).
TABLE-US-00005 Composition/ heat cycle lid Headspace/purge result
1.1/S5 or S4 PTFE coated silicon Air/none A - heavily seal (Fischer
discolored, Scientific, supplied failed to foam, by Schott-Duran,
or inadequate catalogue no. BTF- foaming 675-010C) B - ok 1.3/S4
PTFE coated Minimal/ A - heavily silicone seal Argon discolored
(Fischer Scientific, B - ok supplied by Schott- Duran, catalogue
no. BTF-675-010C). 1.1 S4 Polypropylene (not Air/none A - no
temperature rated) discoloration, foamed but reduced rise volume B
- ok 1.3/S3 aluminium screw Air/none A - heavily cap with black
discolored rubber seal B - ok 1.3/S3 aluminium screw Argon/ A -
discolored cap with black Argon B - ok rubber seal 1.3/S3 aluminium
screw none/Argon B - minor cap with black discoloration rubber
seal
Example 3
Thermally Stable Composition in Presence of Hard Packaging (Wadless
Lids) and Enclosed Atmosphere
[0279] Samples of 1.3 were subject to S3 heating cycle as
follows:
Fisher 30 ml bottle (Fisher Scientific Catalogue no. BTF-605-030W)
with polypropylene lid (not temperature rated)--a) air headspace b)
argon purge and headspace Sterilin 30 ml bottle (Chromacol code
11912-001) with wadless lid--a) air headspace b) argon purge and
headspace Schott Duran 25 ml bottle (Fisher Scientific Catalogue
no. BTF-682-030H) with blue polypropylene lid (rated to 140.degree.
C.)--a) air headspace b) argon purge and headspace
[0280] Following the cycle the samples displayed no black or
coloured residue. The lids on the Sterilin bottles had melted, and
caused catastrophic failure of inverted samples with loss of
containment.
[0281] The Fischer lids had retained a seal but showed signs of a
pressure build-up and had suffered permanent deformation.
[0282] The Schott Duran lids showed no outward signs of stress. 25
ml Schott Duran glass bottles with blue polypropylene lids (25/ISO
thread, lid related autoclavable to 140 C, Fischer Scientific
Catalogue no: BTF-682-030H) moulded from a single piece of
polypropylene part with no additional elastomeric components, were
shown to provide containment for the silicone prepolymers through
the S3 heat sterilisation cycle, even when the bottles were
inverted.
[0283] There was no loss of liquid containment and no visible
degradation with this system following heating. As such this range
of containers was selected as the most appropriate packaging
system.
Example 4
Thermally Stable Composition in Presence of Hard Packaging (Lids)
and Enclosed Atmosphere
[0284] Example 1 highlighted the thermal stability of the
composition under suitable sterilisation conditions, and also the
requirement that the composition be provided in containment
packaging which is thermally stable per se. Examples 2 and CE2 and
3 highlighted the additional requirement that the composition be
provided in specific containment packaging which ensures that the
composition is not contaminated by thermal sterilisation in
presence of certain materials. This Example provides a detailed
assessment of 1.1, 1.2 and 1.3 when heat treated at 123.degree. C.
for 24 hours (S4) and at 134.degree. C. for 6 hours (S3) within a
carefully contained packaging environment.
[0285] Pre-polymers A & B were dispensed into separate 100 ml
bottles made of clear borosilicate glass (Schott Duran) with blue
polypropylene lids (rated autoclavable to 140.degree. C., Fisher
Scientific, Product Code BTF-682-071Q). In each case 100 ml of
pre-polymer was contained in each vessel. This fill volume afforded
a reasonably modest headspace whilst providing sufficient
separation between the upper surface of the pre-polymer and the
lower surface of the lid such that the two did not make direct
contact whilst under thermal load. Inert atmosphere conditions were
imposed degassing with argon, sparging the pre-polymer and purging
the headspace.
[0286] The influence of these heating conditions on the appearance
of the pre-polymers and on selected functional performance
characteristics of the foam curing process was assessed.
[0287] After heat treatment discrete changes in the visual
appearance of 1.1 Part A and 1.2 Part B were observed. In the case
of 1.1, some darkening occurred and in the case of 1.2 suspended
agglomerates of a cloudy gel like species formed which settled on
standing for 8 weeks. No visual changes were observed in either
Part of 1.3 following either of the heat treatment regimes.
[0288] Discrete changes in functional performance were observed for
the heat treated pre-polymers of 1.1, 1.2 and 1.3 when compared to
their unheated controls. Subject to the desired performance
requirements of the system these changes can be considered
acceptable following treatment at both S4 and S3.
[0289] Preferably the conditions of S3 would be recommended for the
heat sterilization of RTV-2 platinum catalysed addition cure
silicone foam pre-polymers as these conditions were found to have
the smallest effect on the visual appearance of the prepolymers and
the smallest effect on the performance of the foaming reactions
during cure.
[0290] The samples were allowed to stand for 8 weeks following heat
treatment before the foaming reactions were assessed. To ensure
thorough mixing following this hold period all samples were
agitated by hand and then placed on a motorized roller to ensure
thorough mixing of the contents.
[0291] For each composition both pre-polymer components (Part A and
Part B) were transferred to a double barrelled mixing system
(Double-Cartridge Prefilled Delivery System (S-System), MedMix
Systems Ag). In each case a 25 ml 1:1 double barrelled cartridge
was used. A cap was applied to the cartridge and the cartridge
positioned vertically within a dye (typically a 150 ml Sterilin
pot) on an electronic balance. One chamber was filled with Part A
to 10 g.+-.0.5 g. An equal volume of Part B was then filled into
the opposing chamber and the height level of the menisci matched by
eye.
[0292] The cartridge pistons were inserted, expelling the air
headspace, so that they were flush with the surface of the
pre-polymers. In this position they were locked and the unit placed
in an internally dry container submerged within a water bath at
25.degree. C. The units were allowed to thermally equilibrate at
25.degree. C. for a minimum of 1 hour before use.
[0293] The assessment reactions were run in a laboratory with
ambient temperature 20.degree. C..+-.2.degree. C. Any apparatus
which would make direct contact with the chemicals during the
dispensing or foaming steps was allowed to thermally equilibrate in
this environment for a minimum of 1 hour (typically mixing heads
and 150 ml Sterilin pots).
[0294] At point of use each cartridge had the tip cap removed, a 16
element helical static mixer applied and it was inserted into a
ratcheted dispenser. The material was rapidly ejected into a
transparent 150 ml Sterilin pot and a timer started at the point
all of the material had been ejected from the dispensing unit.
[0295] Rise time was measured as the time taken to reach the
maximum rise height. In the majority of cases this moment was
punctuated by a bubble collapse running through the upper foam
structure, this resulted in a slight but definite drop in the top
surface of the foam.
[0296] Volume was measured using a liquid displacement method once
a minimum of 10 minutes had been allowed to elapse after the rise
time measurement. The headspace was filled with water and the
volume of liquid measured in a 250 ml measuring cylinder. The
silicone foam was then demoulded from the Sterilin pot, the
Sterilin pot filled with water and the volume of liquid measured in
a 250 ml measuring cylinder. The foam volume was calculated as the
liquid displacement.
[0297] All foaming experiments were run in triplicate (n=3).
[0298] The results are shown in Table 4.1
TABLE-US-00006 TABLE 4.1 Parts A and B treated, containment in
glass bottles with PP lids. Liquids sparged and headspaces purged
with argon. Percentage change in the mean rise times and mean foam
volumes of heat treated samples relative to their unheated
controls. Foam Rise time Rise time volume Foam volume S4 S3 S4 S3
1.1 -23% +10% -30% -18% 1.2 -8% -4% -20% -10% 1.3 +8% +12% -10%
-8%
[0299] Some changes in visual appearance were noticed including 1.1
Part A darkening of the clear component, 1.2 Part B presence of
suspended agglomerates in a cloudy gel. Properties of Parts A and B
subject to S3 conditions were closest to the control properties.
Both S3 and S4 conditions were considered acceptable, S3 conditions
were recommended for heat sterilisation of RTV-2 prepolymers.
Example 5
Thermally Stable Sealant Compositions
[0300] Silpuran 2400/18 A/B (Wacker) is an addition-curing RTV-2
silicone rubber curing to a blue coloured silicone of low hardness.
It has application in flexible moulding applications for
prosthetics.
[0301] Silpuran 2400/18 pre-polymers A & B were dispensed into
separate 100 ml bottles made of clear borosilicate glass (Schott
Duran) with blue polypropylene lids (rated autoclavable to
140.degree. C., Fisher Scientific, Product Code BTF-682-071Q). In
each case 100 ml of pre-polymer was contained in each vessel. This
fill volume afforded a reasonably modest headspace whilst providing
sufficient separation between the upper surface of the pre-polymer
and the lower surface of the lid such that the two did not make
direct contact whilst under thermal load. Inert atmosphere
conditions were imposed degassing with argon, purging the
headspace.
[0302] Materials were subject to heat treatment at 134.degree. C.
for 6 hours (S3) and 123.degree. C. for 24 hours (S4). The samples
were allowed to cool and conditioned overnight at a temperature of
20.degree. C..+-.2.degree. C. Viscosity was measured using a
Brookfield Programmable RVDV-II+Viscometer fitted with Spindle 7. A
set speed of 100 rpm was used for Parts A and for Parts B. The
spindle and temperature probe were thoroughly cleaned (using
ethanol) and allowed to dry before each reading.
% Change in Viscosity Relative to the Un-Heated Control
TABLE-US-00007 [0303] Silpuran 2400/18 A Silpuran 2400/18 B
123.degree. C., 24 hrs/cP 11.36%* 23.91%* 134.degree. C., 6 hrs/cP
9.09%* 17.39%* *Viscometer set speed 100 rpm
[0304] Curing was achieved by placing a 250 ml glass bottle with
extra wide neck (Fisher Scientific, Product Code BTF-630-090N) on
an electronic balance. In each case 100.00 g.+-.0.10 g of Part A
was weighed into the container. To this 100.00 g.+-.0.30 g of the
corresponding Part B was weighed directly into the container. Using
a spatula the system was mixed by hand for 5 minutes and
transferred to an oven pre-heated at 120.degree. C. The system was
cured at 120.degree. C. for 1 hour. Samples were removed from the
oven, allowed to cool and conditioned overnight at a temperature of
20.degree. C..+-.2.degree. C.
[0305] There were no significant differences in the visual
appearance or in the surface tack (as gauged by touch) between the
cured control sample and the cured samples made from pre-polymers
subject to the S3 and S4 heating cycles.
[0306] Penetration was measured using a Setamatic Penetrometer with
automatic release, timing device and standard 47.5 g plunger. The
instrument was fitted with a hollow plastic cone with a stainless
steel tip of mass 15 g. A dwell time of 60 seconds was used. All
measurements were recorded in triplicate (n=3).
TABLE-US-00008 Relative mass Mean of parts penetration/ A B 1/10 mm
Silpuran 2400/18 A/B - control 50.0% 50.0% 51 (SD 1) Silpuran
2400/18 A/B - 134.degree. C., 50.0% 50.0% 118 (SD 1) 6 hrs Silpuran
2400/18 A/B - 123.degree. C., 50.0% 50.0% 87 (SD 1) 24 hrs
[0307] Subject to the desired performance requirements of the
system these changes can be considered acceptable following
treatment at both S3 and S4.
Example 6
Thermally Stable Sealant Compositions
Example 6a
[0308] Mepiseal.TM. (Molnlycke), a commercially available RTV-2
polyorganosiloxane sealant composition, was obtained as sold in a
double barrel dispensing syringe dispensing 3 ml of composition.
The cartridge has an integrated mixing head and integrated twist
tip seal. The units are packaged within a secondary plastic bag.
The composition is indicated for sealing a NPWT drape, and has an
indicated cure time of 9 minutes.
[0309] Syringes incorporating composition were subject to S3
thermal sterilisation cycle and S4 thermal sterilisation cycle. Of
these, 3 removed from their secondary pouches and 3 remaining in
their secondary pouches were subject to S3. After 2.5 hours the
plunger and piston were seen to have melted in all samples
regardless of whether they were in the polymer pouches or not.
After 6 hours no further change in the state of the syringes was
observed. Other than the plungers, the remaining external
components appeared intact. The pouches had not burst, although
they had bonded to parts of the syringe inside. Upon opening one of
these pouches it was observed that where the syringe had melted,
direct contact could be made with the prepolymers. The prepolymers
were no longer sealed in the syringe but were exposed. The
viability and functional properties of the silicone prepolymers
could not be assessed as it was not possible to dispense these from
the syringe.
[0310] A further 4 samples were subject to S4 thermal
sterilisation, 2 in their secondary pouches and 2 removed from
their secondary pouches. After 24 hours the plungers did not fully
melt however warping of the plungers was observed and the plungers
moved freely in the barrel and no longer formed a seal. When
compared to a non-heat sterilised Mepiseal.TM. syringe, it was
observed that a colour change had occurred in the silicone
prepolymers after being heat treated at both temperatures.
[0311] Manual kinetic time for the non-heat treated sample was 12
minutes and 20 seconds. The S4 heat treated composition was
dispensed and allowed to cure and manual kinetic time tested by
finger touch to the dispensed composition. If composition is found
to transfer to the finger this indicates that the manual kinetic
point has not been reached and the composition has not (fully)
cured.
[0312] The experiment to determine manual kinetic time for the S4
heat treated sample was aborted after 72 hours as the manual
kinetic point had not been reached.
[0313] The composition was therefore shown to be thermally unstable
at S4 conditions, the mildest terminal sterilisation conditions
which we had been able to achieve, as a result of failure of the
packaging under S3 and S4 conditions. Packaging failure allowed
exposure to air and moisture, due to rupture of the seal and this
in turn led to contamination of the composition.
Example 6b
[0314] Mepiseal.TM. (Molnlycke), as in Example 7a was dispensed
into 2 borosilicate glass vials and enclosed in manner according to
Example 4 above and subject to S3 thermal sterilisation cycle. The
composition was then mixed in standard manner and the manual
kinetic time recorded. The manual kinetic time was considered
acceptable following treatment at S3.
[0315] This indicates that the Mepiseal.TM. composition is
thermally stable to conditions providing terminal sterility, if
provided in thermally stable packaging in the absence of excess
air.
Example 8
Thermally Stable Adhesive Compositions
[0316] Silpuran 2111 A/B (Wacker) is a commercially available
2-part, addition-curing silicone composition curing to a soft,
tacky silicone adhesive. It is suitable for use in wound
dressings.
[0317] Silpuran 2111 pre-polymers A & B were dispensed into
separate 100 ml bottles made of clear borosilicate glass (Schott
Duran) with blue polypropylene lids (rated autoclavable to
140.degree. C., Fisher Scientific, Product Code BTF-682-071Q). In
each case 100 ml of pre-polymer was contained in each vessel. This
fill volume afforded a reasonably modest headspace whilst providing
sufficient separation between the upper surface of the pre-polymer
and the lower surface of the lid such that the two did not make
direct contact whilst under thermal load. Inert atmosphere
conditions were imposed degassing with argon, purging the
headspace.
[0318] Materials were subject to heat treatment at 134.degree. C.
for 6 hours (S3) and 123.degree. C. for 24 hours (S4). The samples
were allowed to cool and conditioned overnight at a temperature of
20.degree. C..+-.2.degree. C. Viscosity was measured using a
Brookfield Programmable RVDV-II+Viscometer fitted with Spindle 7. A
set speed of 100 rpm was used for Parts A and a set speed of 50 rpm
was used for Parts B. The spindle and temperature probe were
thoroughly cleaned (using ethanol) and allowed to dry before each
reading.
% Change in Viscosity Relative to the Un-Heated Control
TABLE-US-00009 [0319] Silpuran 2111 A Silpuran 2111 B 123.degree.
C., 24 hrs 0.36%* 1.47%.sup..dagger. 134.degree. C., 6 hrs 2.00%*
-0.15%.dagger. *Viscometer set speed 100 rpm
.sup..dagger.Viscometer set speed 50 rpm
[0320] Curing was achieved by placing a 250 ml glass bottle with
extra wide neck (Fisher Scientific, Product Code BTF-630-090N) on
an electronic balance. In each case 100.00 g.+-.0.10 g of Part A
was weighed into the container. To this 100.00 g.+-.0.30 g of the
corresponding Part B was weighed directly into the container. Using
a spatula the system was mixed by hand for 5 minutes and
transferred to an oven pre-heated at 120.degree. C. The system was
cured at 120.degree. C. for 1 hour. Samples were removed from the
oven, allowed to cool and conditioned overnight at a temperature of
20.degree. C..+-.2.degree. C.
[0321] There were no significant differences in the visual
appearance or in the surface tack (as gauged by touch) between the
cured control sample and the cured samples made from pre-polymers
subject to the S3 and S4 heating cycles.
[0322] Penetration was measured using a Setamatic Penetrometer with
automatic release, timing device and standard 47.5 g plunger. The
instrument was fitted with a hollow plastic cone with a stainless
steel tip of mass 15 g. A dwell time of 60 seconds was used. All
measurements were recorded in triplicate (n=3).
TABLE-US-00010 Relative mass Mean of parts penetration/ A B 1/10 mm
Silpuran 2111 A/B - control 50.0% 50.0% 200 (SD 3) Silpuran 2111
A/B - 134.degree. C., 6 hrs 50.1% 49.9% 206 (SD 3) Silpuran 2111
A/B - 123.degree. C., 24 hrs 50.0% 50.0% 211 (SD 4)
[0323] Subject to the desired performance requirements of the
system these changes can be considered acceptable following
treatment at both S3 and S4.
Example 9
Thermally Stable NPWT Foamable Compositions
[0324] The cured foamed Example 1.2 composition Rhodorsil RT Foam
3240 was able to transmit a negative pressure with pressure drop,
however this was not totally reproduceable. In some cases the
transmitted pressure would be acceptable for NPWT.
[0325] The modified Example 1.3 composition, Rhodorsil NPWT,
delivered a cured foam which was able to transmit negative pressure
for NPWT.
[0326] Certain embodiments provide a route to sterile RTV-2
compositions at temperatures below that of the accepted standard
dry heat cycle which removes packaging constraints and thereby
provides a route to commercially viable packaging.
[0327] It will be appreciated that various embodiments and
applications of the composite are envisaged and are not limited to
the embodiments and applications hereinbefore described but may be
varied in construction, detail and application within the scope of
the appended claims.
* * * * *