Composition I-II 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 preventing contamination, the at least one Part A comprising: (i) one or more alkenyl-group containing prepolymers having at least one alkenyl group or moiety per molecule, and the at least one Part B comprising: (ii) one or more SiH-containing prepolymers having at least one Si—H unit per molecule; the composition additionally comprising: (iii) a catalyst for curing by addition of alkenyl-containing prepolymer (i) to SiH-containing prepolymer (ii), wherein prepolymer (ii) is substantially absent from Part A and prepolymer (i) is substantially absent from Part B, 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).

Claims

1. A curable composition apportioned between at least one Part A and at least one Part B, the composition comprising: the at least one Part A comprising one or more alkenyl-group containing polymers having at least one, or at least two, alkenyl group or moiety per molecule, the at least one Part B comprising one or more SiH-containing polymers having at least one, or at least two, Si—H unit or moiety per molecule, a catalyst for curing by addition of an alkenyl-containing polymer to a SiH-containing polymer, and a blowing agent configured to evolve gas as part of or during the curing reaction, wherein the SiH-containing polymer is absent from Part A and the alkenyl-group containing polymer is absent from Part B or Part B incorporates a trace amount of the alkenyl-group containing polymer represented as a molar ratio (Si—H unit or moiety)/(alkenyl unit or moiety) of greater than or equal to 2000.

2. A method of preparing a composition as claimed in claim 1, comprising combining the one or more alkenyl-group containing polymers, the one or more SiH-containing polymers, the catalyst, and the blowing agent to form the at the least one Part A and the at least one Part B.

3. A method of sterilizing a composition as claimed in claim 1, comprising irradiating the composition Parts in a sterilizing dose or irradiating the at least one of Part A and the at least one Part B and sterilizing other one or more Parts by alternative means.

4. 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.

5. An elastomer comprising the cured or crosslinked composition of claim 1.

6. An elastomer as claimed in claim 5, wherein the elastomer comprises a porous foam, adhesive, or sealant.

7. An elastomer as claimed in claim 5, wherein the elastomer comprises a foamed cured wound filler, wound packing material, cavity foam dressing.

8. A composition dispensing device comprising a composition as claimed in claim 1.

9. A device as claimed in claim 8, further comprising a mixing head configured to receive two or more cartridges comprising Parts A and B.

10. A method for treating a wound site using a composition as claimed in claim 1, the method comprising: dispensing a terminally sterile foamable composition into at least a portion of the wound site, wherein the foamable composition forms a porous foam material configured to transmit negative pressure; covering the wound site with a fluid-tight drape, the drape covering at least a portion of the dispensed terminally sterile composition; forming a fluid-tight seal over the wound site; and applying negative pressure to the wound site from a source of negative pressure.

11. The method of claim 10, further comprising connecting the source of negative pressure by connecting a conduit to the wound site through or under the fluid-tight seal.

12. A NPWT kit comprising a fluid-tight wound dressing, a dispensible or releasable terminally sterile adhesive or sealant composition as claimed in claim 1, and an attachment for a vacuum pump to supply negative pressure to the dressing.

13. A device for dispensing the composition as claimed in claim 1, the device comprising a mixing head configured to receive two or more cartridges comprising Parts A and B.

14. A device of claim 13, the device comprising a double barreled syringe configured for loading with 40 g of the polymers.

15. A method for treating a wound site using a composition as claimed in claim 1, the method comprising: dispensing a terminally sterile composition around at least a portion of the wound site, wherein the composition comprises a first part and a second part that when combined form a material configured to make a fluid-tight seal; covering the wound site with a fluid-tight drape, the drape covering at least a portion of the dispensed terminally sterile composition; forming a fluid-tight seal over the wound site; and applying negative pressure to the wound site from a source of negative pressure.

16. The method of claim 15, further comprising mixing the first and second parts of the terminally sterile foamable composition while dispensing the composition.

17. A method for treating a wound site using a composition as claimed in claim 1, the method comprising: applying a dressing to the wound site; releasing a first part of a terminally sterile composition from a support about or around at least a portion of the wound site and exposing the first part; exposing a second part of the terminally sterile composition supported on a fluid-tight drape; covering the wound site with the drape, thereby contacting and adhering the exposed first and second parts and adhering the drape about or around the wound site; forming a fluid-tight seal over the wound site; and applying negative pressure to the wound site from a source of negative pressure.

Description

BRIEF DESCRIPTION OF THE DRAWINGS

(1) Embodiments of the invention will now be illustrated in non limiting manner with reference to the Figures in which

(2) FIGS. 1A-B and 2A-B illustrate a NPWT foam filler wound dressing;

(3) FIGS. 3A-C and 7, 8, 9 and 10 illustrate the use and application of a dispensible sterile foam filler wound dressing onto a patient;

(4) FIGS. 4A, 5 and 6 illustrate a kit including a sealant composition and wound dressing;

(5) FIGS. 11A to 15B illustrate the use and application of an embodiment of a wound cover kit, apparatus and sealant onto a patient.

(6) 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 a) and covered over and sealed with an adhesive flexible sheet (a drape, 3) that is fairly impermeable to fluids.

(7) 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.

(8) 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.

(9) 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.

(10) FIG. 5 shows a variant of FIG. 4, in which the pump (8) is removably connected (5a) through aperture (5b) in the drape (3).

(11) 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.

(12) 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.

(13) FIG. 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.

(14) 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

(15) Preparation of Composition

(16) RTV-2 polydimethylsiloxane composition Cavi-Care is a commercially available (Smith & Nephew) RTV-2 Pt catalysed foamable silicone elastomer having 30-105 seconds rise time, packaged as Parts A and B in foil pouches formed from aluminium foil laminated to either face with PE.

(17) Rhodorsil RT Foam 3240 A/B (Bluestar Silicones) is a RTV-2 Pt catalysed foamable silicone elastomer having 7.5 minutes rise time.

(18) Sterilisation

(19) The compositions were subjected to gamma irradiation using a Co source irradiation and e-beam irradiation at 10 MeV, at 10, 15, 20 and 25 kGy.

(20) After sterilisation the following were determined and compared with unsterilised polymer:

(21) Viscosity

(22) In each case, the composition Part B formed a solid elastomer (gamma) and underwent an increase in viscosity (e-beam).

(23) The composition Part A underwent an increase in viscosity with either radiation means, with gamma at 25-42 kGy, increase in viscosity was 230% (Cavi-Care) or 850% (Rhodorsil).

(24) Curing

(25) Gamma irradiated Cavi-Care and Rhodorsil Part B could not be subsequently reacted to provide an acceptable foamed cured product. Irradiated Rhodorsil Part A cured with non-irradiated Part B gave an unacceptsbly long cure time, in the case of gamma and e-beam.

(26) Foam Density and Compressibility

(27) not tested.

(28) Sterility Testing

(29) This was not tested as the sterilised composition were not curable.

(30) The gamma irradiation dose is expected to have achieved sterilisation.

Example 1—A Two Part Composition and a Method for its Preparation Will Hereinafter be Described

(31) The viscosities of the following examples correspond to a dynamic viscosity quantity which was measured, in a way known per se, at 25° C. The viscosities were measured using a Brookfield viscosimeter according to the instructions of the AFNOR NFT 76 106 standard of May 1982. These viscosities correspond to a “newtonian” dynamic viscosity quantity at 25° C., that is to say the dynamic viscosity which is measured, in a way known per se, at a shear rate gradient which is sufficiently low for the viscosity measured to be independent of the rate gradient.

(32) Some two-component compositions comprising parts P1 and P2, the composition of which are described in Table 1, were prepared:

(33) 1) Components in Part a of the Tested Compositions:

(34) M=(CH.sub.3).sub.3SiO.sub.1/2, M.sup.Vi=(CH.sub.3).sub.2ViSiO.sub.1/2 or (CH.sub.2═CH—)(CH.sub.3).sub.2SiO.sub.1/2, D.sup.Vi=(CH.sub.3)(Vi)SiO.sub.2/2 or (CH.sub.2═CH—)(CH.sub.3)SiO.sub.2/2 and Q=SiO.sub.4/2 a: Vinylated polyorganosiloxane resin comprising M, D.sup.Vi and Q siloxyl groups (also named as «MD.sup.ViQ» resin) with: b1: polydimethylsiloxane blocked at each of the chain ends by a M.sup.Vi unit and having a viscosity of 3500 mPa.Math.s at 25° C. b2: polydimethylsiloxane blocked at each of the chain ends by a M.sup.Vi unit and having a viscosity of 100 000 mPa.Math.s at 25° C. b3: polydimethylsiloxane blocked at each of the chain ends by a M.sup.Vi unit and having a viscosity of 1 500 mPa.Math.s at 25° C. b4: polydimethylsiloxane blocked at each of the chain ends by a M.sup.Vi unit and having a viscosity of 230 mPa.Math.s at 25° C. c1: diatomeceous earth, sold under the trade name CELITE-SF©. c2: Fumed treated silica having a low specific surface of 30 m.sup.2/g (BET), sold under the trade name AEROSIL® RY50 d: Hexanol. e: Karstedt platinum catalyst. f1: polydimethylsiloxane blocked at each of the chain ends by a M unit and having a viscosity of 1000 mPa.Math.s at 25° C. g: poly(vinylmethyl)(dimethyl)siloxane oil having a content of D.sup.Vi unit of 2% by weight and a content of M.sup.Vi unit of 0,4% by weight.
2) Components in Part B of the Tested Compositions: a: Vinylated polyorganosiloxane resin comprising M, D.sup.Vi and Q siloxyl groups (also named as «MD.sup.ViQ» resin). b1: polydimethylsiloxane blocked at each of the chain ends by a (CH.sub.3).sub.2ViSiO.sub.1/2 unit and having a viscosity of 3500 mPa.Math.s at 25° C. b2: polydimethylsiloxane blocked at each of the chain ends by a (CH.sub.3).sub.2ViSiO.sub.1/2 unit and having a viscosity of 100 000 mPa.Math.s at 25° C. f1: polydimethylsiloxane blocked at each of the chain ends by a (CH.sub.3).sub.3SiO.sub.1/2 unit and having a viscosity of 1000 mPa.Math.s at 25° C. f2: polydimethylsiloxane blocked at each of the chain ends by a (CH.sub.3).sub.3SiO.sub.1/2 unit and having a viscosity of 100 000 mPa.Math.s at 25° C. i: polydimethylsiloxane oil blocked at each of the chain ends by a (CH.sub.3).sub.2HSiO.sub.0.5 unit h: polymethylhydrogenosiloxane oil blocked at each of the chain ends by a (CH.sub.3).sub.3SiO.sub.0.5 unit. j: solution comprising 1% of ethynylcyclohexanol in a polydimethylsiloxane oil blocked at each of the chain ends by (CH.sub.3).sub.2ViSiO.sub.1/2 units, having a viscosity of 600 mPa.Math.s at 25° C.

(35) The compositions tested are described in Table1 below:

(36) TABLE-US-00002 TABLE 1 COMPOSITIONS: Parts by weight Ingredients Ex. Ex. Ex. Part A Ex. 1 2 3 4 a 20.39 15.09 19.13 20.17 b1 61.17 45.26 57.39 60.50 b2 12.51 12.49 b3 35.19 b4 15.00 c1 c2 0.94 1.26 1.25 1.87 d 3.63 3.11 3.62 3.62 e 0.11 0.10 0.11 0.11 f1 g 1.25 3.50 1.25 Ingredients Ex. Ex. Ex. Part B (C*) Ex. 1 2 3 4 a b1 b2 f1 f2 36.88 36.88 36.88 36.88 i 17.68 17.68 17.68 17.68 h 45.45 45.45 45.45 45.45 j Ratio by 80/20 80/20 80/20 80/20 weight Part A/ Part(s)B, C* Ingredients Ex. Comparison Ex. Part A 5 Ex. 6 Ex. 7 8 a 15.01 18.73 18.73 15.59 b1 45.02 56.20 56.20 46.76 b2 5.99 5.99 b3 35.00 36.35 b4 c1 9.99 9.99 c2 1.25 1.30 d 3.09 4.10 4.10 0 e 0.10 0.09 0.09 0.003 f1 4.90 4.90 g 18.73 Ingredients Ex. Comparison Ex. Part B (C*) 5 Ex. 6 Ex. 7 8 a 9.99 * 9.99 b1 29.97* 29.97 b2 0.50 29.97* 29.97 f1 4.99 * 4.99 f2 36.88 i 27.89 6.99 6.99 17.68 h 71.61 17.98 17.98 45.45 j 0.10* 0.10 Ratio by 86.3/13.7 100/ 100/100 90/10 weight 24.97/75.03 Part A/ Part(s)B, C*

(37) In Example 6, the composition was made by mixing the three Parts A, B and C (components of Part C are indicated by “*” term).

(38) Examples 1 to 7 are foaming.

(39) Example 8 is non foaming.

(40) 3) Sterilization and Crosslinking

(41) Parts A and B were irradiated by gamma, e-beam or X-Ray at various doses included between 10 kGy to 35 kGy.

(42) After sterilisation, each Part was then mixed with the sterilized (or with the non-sterilised such as in Example 6 or 8) corresponding part, according to the ratio mentioned in the Table 1. After curing, the resultant solid or foam elastomers are evaluated and compared with unsterilised elastomers (results recorded in Tables 2 to 5).

(43) 4) Tests

(44) As shown by results of Examples 1, 2, 3, 4 and 6, it is possible to irradiate Parts A and B by gamma, e-beam or X-Ray even at high doses (10 kGy to 35 kGy) with no or acceptable slight increase in viscosity. Moreover, the properties of the elastomeric foams are similar to those of the unsterilised foams. The addition of inert silicone oil as diluent to Part B enabled the viscosity and volume of Parts A and B to be balanced.

(45) The Comparative Example 7 demonstrates that the presence in Part B of polysiloxanes having SiH units and of polysiloxanes having SiVinyl units leads to gel or cured pre-polymer after sterilization of Part B. Thus, it is not possible to mix Parts A and B in order to produce the foam. Nevertheless, the Example 5 demonstrates that the presence of 0.5% by weight of a polydimethylsiloxane blocked at each of the chain ends by a (CH.sub.3).sub.2ViSiO.sub.1/2 (M.sup.Vi)unit is acceptable.

(46) TABLE-US-00003 TABLE 2 Example 1 Example 2 Example 3 Irradiation technique None Gamma Gamma None Gamma Gamma None Gamma Irradiation dose on Part A (kGy) 0 10.6 25.9 0 25.2 35.6 0 25.4 Irradiation dose on Part B (kGy) 0 10.6 25.9 0 25.2 35.6 0 25.4 Viscosity of Part A (mPa .Math. s) 4800 6500 21570 2000 4200 8200 1600 5200 Viscosity of Part B (mPa .Math. s) 1750 2100 2430 1700 2600 2500 1700 2700 Density of cured foam (g/cm.sup.3) 0.2 0.23 0.21 0.2 0.27 0.23 0.24 0.26 Hardness after 15′ at 23° C. (Sh00) 15 13 15 19 21 16 25 20 Hardness after 1 day at 23° C. (Sh00) 30 35 31 31 36 30 41 37 Manual Kinetic at 23° C. 2′55″ 3′25″ 2′45 2′05″ 2′55″ 2′05″ 2′55″ 2′25″

(47) TABLE-US-00004 TABLE 3 Example 4 Example 5 Example 6 (part P3 was not irradiated) Irradiation technique None X-Ray None Gamma e-beam None Gamma e-beam Irradiation dose on 0 26.3 0 25.1 18.1-31.3 0 0 0 Part A (kGy) Irradiation dose on 0 24.4 0 25.1 18.1-31.3 0 25.0 25.2-30.4 Part B (kGy) Viscosity of Part A 5300 17300 1700 3800 3000 5120 5120 5120 (mPa .Math. s) Viscosity of Part B 1600 2700 50 150 40 <5000 <5000 <5000 (mPa .Math. s) Density of cured 0.19 0.23 0.19 0.26 0.24 0.17 0.18 0.2 foam (g/cm.sup.3) Hardness after 15′ at 13 13 22 25 25 0 0 0 23° C. (Sh00) Hardness after 1 day 31 33 40 39 42 38 37 37 at 23° C. (Sh00) Manual Kinetic at 3′15″ 2′30″ 2′15″ 2′40″ 3′30″ 5′ 4′35″ 4′30″ 23° C.

(48) TABLE-US-00005 TABLE 4 Comparison Example 7 Irradiation technique None Gamma Gamma e-beam Irradiation dose on Part A (kGy) 0 10.1 25.0 23.7-23.8 Irradiation dose on Part B (kGy) 0 10.1 25.0 22.6-23.1 Viscosity of Part A (mPa .Math. s) 5120 6960 45200 11000 Viscosity of Part B (mPa .Math. s) 5600 Gel Cured Gel Density of cured foam (g/cm.sup.3) 0.17 / / / Hardness after 15′ at 23° C. (Sh00) 0 / / / Hardness after 1 day at 23° C. 38 / / / (Sh00) Manual Kinetic at 23° C. 5' / / /

(49) As shown by results in Table 5, it is possible to irradiate Parts A and B by gamma or e-beam even at high doses (25 kGy) with no or acceptable slight increase in viscosity. Moreover, the properties of the elastomers are similar to those of the unsterilised polymers.

(50) TABLE-US-00006 TABLE 5 Example 8 (non-foaming) Irradiation technique None Gamma e-beam Gamma e-beam Irradiation dose on Part A (kGy) 0 25.1 18.1-31.3 0 0 Irradiation dose on Part B (kGy) 0 25.1 18.1-31.3 25. 18.1-31.3 Viscosity of Part A (mPa .Math. s) 2400 5100 3800 2400 2400 Viscosity of Part B (mPa .Math. s) 1800 2400 2500 2400 2500 Pot-life at 23° C. 2h05 / / 2h05 2h10 Hardness after 1 h at 150° C. (ShA) 35 / / 34 30 Mechanical properties after T/S (MPa) 1.8 / / 1.7 1.2 1 h at 150° C. E/B (%) 144 / / 143 136 Tr/S (N/mm) 2.2 / / 2.3 2.3

Example 3—Determination of Tolerated Contaminant Prepolymer (i) in Part B

(51) Compositions were prepared incorporating different amounts of vinyl in Part B and irradiated by gamma or e-beam at 25 kGy.

(52) The composition tested are described in Table 6 below:

(53) TABLE-US-00007 TABLE 6 COMPOSITIONS: Parts by weight Components Part A Example 9 Part P1 a 15.01 b1 45.02 b3 35.00 c2 1.25 d 3.09 e 0.10 Components Part B Part P2 b3 0.99 i 27.75 h 71.26 Ratio by weight 86.3/13.7 Part A/Part(s) B

(54) The results are as follows:

(55) TABLE-US-00008 Composition Effect of irradiation % wt (i) in Part B H/Vi ratio Comparison unacceptable <1000 Example 7 Example 9 acceptable, slight (1% of short Vinyl 10 000-15 000 effect on density chain) (0.18 to 0.28) Example 5 acceptable 0.5% of long chain = 80 000-120 000 Example 5

(56) These results show that a low level of prepolymer (i) is acceptable in Part B, which is insufficient to influence the properties of the composition.

(57) We determined a boundary level at which prepolymer (i) is unacceptable in Part B.

(58) At H/Vi ratio=2,000 the properties of Part B are altered but the composition remains functional.

(59) Within this boundary level, at H/Vi ratio=5,000 the properties of Part B are minimally changed and function is good.

(60) Within this preferred level, at H/Vi=10,000 the properties of Part B are substantially unchanged and function is excellent.