Agent for salting out active principles in dressings containing at least one of fatty substance

Abstract

The present invention relates to the use, as an agent for salting out an active substance in a composition for a dressing, of a copolymer of a salt of 2-methyl-2-[(1-oxo-2-propenyl)amino]-1-propanesulphonic acid and the 2-hydroxyethyl ester of propenoic acid. It also relates to dressings of the type comprising at least one fatty substance and/or an elastomeric matrix and at least one active substance, which incorporate the aforementioned copolymer.

Claims

1. A dressing comprising a mass, wherein the mass comprises a hydrocolloid in an amount of between 2 and 20% by weight of the mass, at least one selected from the group consisting of a fatty substance and an elastomeric matrix, at least one active substance, and a copolymer of a salt of 2-methyl-2-[(1-oxo-2-propenyl)amino]-1-propanesulfonic acid and of 2-hydroxyethylpropenoate ester, wherein the copolymer is included in an amount sufficient for increasing an amount of the active substance that is released from the dressing as compared to that of a corresponding dressing that does not comprise the copolymer, wherein the amount of the copolymer included in the dressing is between 1% to 20% by weight, and wherein the amount of the active substance included in the dressing is between 0.01% and 15% by weight.

2. The dressing as claimed in claim 1, wherein the salt of 2-methyl-2-[(1-oxo-2-propenyl)amino]-1-propanesulfonic acid is a sodium salt.

3. The dressing as claimed in claim 1, wherein said active substance is selected from the group consisting of bactericidal agents, bacteriostatic agents, agents for promoting healing, enzymes for promoting wound cleaning, protease inhibitors, metalloprotease inhibitors, painkillers, local anesthetics and nonsteroidal anti-inflammatory drugs.

4. The dressing as claimed in claim 1, which comprises between 1% and 10% by weight of said copolymer.

5. The dressing as claimed in claim 1, which comprises between 3% and 8% by weight of said active substance.

6. A method for releasing an active substance from a dressing composition that comprises a mass, wherein the mass comprises a hydrocolloid in an amount of between 2 and 20% by weight of the mass and, at least one selected from the group consisting of a fatty substance and an elastomeric matrix and at least one active substance, the method comprising incorporating a copolymer of a salt of 2-methyl-2-[(1-oxo-2-propenyl)amino]-1-propanesulfonic acid and of 2-hydroxyethylpropenoate ester in said dressing composition in an amount sufficient for increasing an amount of the active substance that is released from the dressing as compared to that of a corresponding dressing that does not comprise the copolymer, wherein the amount of the copolymer incorporated in the dressing is between 1% to 20% by weight, and wherein the amount of the active substance included in the dressing is between 0.01% and 15% by weight.

7. The method as claimed in claim 6, wherein said salt of 2-methyl-2-[(1-oxo-2-propenyl)amino]-1-propanesulfonic acid is a sodium salt.

8. The method as claimed in claim 6, wherein said active substance is selected from the group consisting of bactericidal agents, bacteriostatic agents, agents for promoting healing, enzymes for promoting wound cleaning, protease inhibitors, metalloprotease inhibitors, painkillers, local anesthetics and nonsteroidal anti-inflammatory drugs.

9. The method as claimed in claim 6, wherein the composition comprises an elastomeric matrix.

10. The dressing as claimed in claim 3, wherein said active substance is a bactericidal or bacteriostatic agent.

11. The dressing as claimed in claim 10, wherein said active substance is selected from the group consisting of: chloramine, chlorhexidine, silver salts, zinc salts, metronidazole and penicillin.

12. The dressing as claimed in claim 11, wherein said active substance is silver salts or zinc salts.

13. The dressing as claimed in claim 12, wherein said active substance is silver salts.

14. The dressing as claimed in claim 3, wherein said active substance is an agent for promoting healing.

15. The dressing as claimed in claim 14, wherein said active substance is potassium sucrose octasulfate.

16. The dressing as claimed in claim 3, wherein said active substance is a painkiller or local anesthetic.

17. The dressing as claimed in claim 16, wherein said active substance is lidocaine or cinchocaine.

18. The dressing as claimed in claim 3, wherein said active substance is a nonsteroidal anti-inflammatory drug.

19. The dressing as claimed in claim 18, wherein said active substance is selected from the group consisting of: ibuprofen, ketoprofen, fenoprofen, and diclofenac.

20. The dressing as claimed in claim 1, wherein the hydrocolloid is at least one selected from the group consisting of pectin, alginate, a natural plant gum, a cellulose derivative or an alkali metal salt thereof, and a superabsorbent.

21. The dressing as claimed in claim 1, wherein the hydrocolloid is a carboxymethylcellulose or a sodium or calcium salt thereof.

22. The dressing as claimed in claim 21, wherein the fatty substance is a paraffin oil, petroleum jelly, or a mineral oil formed from compounds of paraffinic, naphthenic or aromatic nature.

23. The dressing as claimed in claim 22, wherein the active agent is a bacteriostatic silver salt, potassium sucrose octasulfate, lidocaine, cinchocaine, or a non-steroidal antiinflammatory drug.

Description

DEMONSTRATION OF THE PROPERTIES OF THE COPOLYMER USED IN THE CONTEXT OF THE INVENTION

a. Constituents Used

(1) The following constituents were used in order to prepare the various dressings of the present invention:

(2) Sepinov EMT 10: a copolymer of a salt of 2-methyl-2-[(1-oxo-2-propenyl)amino]-1-propanesulfonic acid and of 2-hydroxyethylpropenoate ester, sold by the company SEPPIC.

(3) Kraton G 1654 and G 1651: high-molecular-weight styrene-ethylene-butylene-styrene (S-EB-S) sold by the company Kraton.

(4) Kraton D1111K: styrene-isoprene-styrene (SIS) copolymer containing at least 22% of polystyrene, sold by the company Kraton.

(5) Ondina 917: a mineral oil sold by the company Shell.

(6) Irganox 1010: pentaerythritol tetrakis(3-(3,5-di-tert-butyl-4-hydroxy-phenyl)propionate) sold by the company Ciba Specialty Chemicals.

(7) Codex A petroleum jelly: petroleum jelly sold by the company Aiglon.

(8) CMC Blanose 7H4XF: sodium carboxymethylcellulose sold by the company Hercules.

(9) Luquasorb 1003: superabsorbent polymer of sodium polyacrylate, sold by BASF.

(10) Silver sulfadiazine: sold by the company Argenol Bentley.

(11) Potassium sucrose octasulfate: sold by the company Euticals.

b1. Production of Elastomeric Masses

Examples 1 to 8

(12) The elastomeric masses of Examples 1 to 8 were prepared by mixing in a Z-blade mixer. The setpoint temperature of Examples 3 and 4 was 140 C., that of Examples 1, 2 and 5 to 8 was 105 C. 1. The styrene-ethylenebutylene-styrene or styrene-isoprene-styrene triblock elastomers were mixed with half the mineral oil and with the antioxidant. 2. At 30 minutes, the petroleum jelly was added to the mixture. 3. At 40 minutes, the rest of the mineral oil was added. 4. At 55 minutes, the sodium carboxymethylcellulose or the superabsorbent polymer, as appropriate, the active substance, optionally the tackifying resin and, where appropriate, the Sepinov EMT 10 copolymer were added. The mixer was emptied at 70 minutes.

Example 9

(13) The elastomeric mass of Example 9 containing the Sepinov EMT 10 copolymer and potassium sucrose octasulfate (sold by the company Euticals) as active substance was prepared by mixing in a Z-blade mixer at a setpoint temperature of 110 C. according to the following process: 1. The petroleum jelly (codex A petroleum jelly sold by the company Aiglon) and the mineral oil (Ondina 917 sold by the company Shell) were mixed at a temperature of 89 C. 2. At 7 minutes, the copolymer was added. 3. At 12 minutes, the sodium carboxymethylcellulose (CMC Blanose 7H4XF sold by the company Hercules) and the active substance were added. 4. At 20 minutes, the high-molecular-weight S-EB-S (Kraton G 1654 sold by the company Kraton) and the antioxidant (Irganox 1010 sold by the company Ciba Specialty Chemicals) were added. The temperature of the mixture was then 106 C. 5. At 60 minutes, the tackifying resin (Escorez 5380 sold by the company Exxon Mobil Chemical) was added. The mixer was emptied at 80 minutes.

Example 10

(14) The elastomeric mass of example 10 containing potassium sucrose octasulfate (sold by the company Euticals) as active substance was prepared by mixing in a Z-blade mixer at a setpoint temperature of 110 C. according to the following process: 1. The petroleum jelly (codex A petroleum jelly sold by the company Aiglon) and the mineral oil (Ondina 917 sold by the company Shell) were mixed at a temperature of 89 C. 2. At 3 minutes, the sodium carboxymethylcellulose (CMC Blanose 7H4XF sold by the company Hercules) and the active substance were added. 3. At 10 minutes, the high-molecular-weight S-EB-S (Kraton G 1654 sold by the company Kraton) and the antioxidant (Irganox 1010 sold by the company Ciba Specialty Chemicals) were added. The temperature of the mixture was then 104 C. 4. At 40 minutes, the tackifying resin (Escorez 5380 sold by the company Exxon Mobil Chemical) was added. The mixer was emptied at 55 minutes.

Example 11

(15) The elastomeric mass of example 11 containing the Sepinov EMT 10 copolymer and silver sulfadiazine (sold by the company Argenol Bentley) as active substance was prepared by mixing in a Z-blade mixer at a setpoint temperature of 130 C. according to the following process: 1. The Sepinov EMT 10 copolymer and the mineral oil (Ondina 917 sold by the company Shell) were mixed at a temperature of 110 C. 2. At 5 minutes, the sodium carboxymethylcellulose (CMC Blanose 7H4XF sold by the company Hercules), the active substance and the petroleum jelly (codex A petroleum jelly sold by the company Aiglon) were added. 3. At 12 minutes, the high-molecular-weight S-EB-S (Kraton G 1651 sold by the company Kraton) and the antioxidant (Irganox 1010 sold by the company Ciba Specialty Chemicals) were added. The temperature of the mixture was then 106 C. 4. At 55 minutes, the tackifying resin (Escorez 5380 sold by the company Exxon Mobil Chemical) was added. The mixer was emptied at 70 minutes.

Example 12

(16) The elastomeric mass of example 12 containing silver sulfadiazine (sold by the company Argenol Bentley) as active substance was prepared by mixing in a Z-blade mixer at a setpoint temperature of 130 C. according to the following process: 1. The mineral oil (Ondina 917 sold by the company Shell), the sodium carboxymethylcellulose (CMC Blanose 7H4XF sold by the company Hercules) and the active substance were mixed at a temperature of 92 C. 2. At 2 minutes, the petroleum jelly (codex A petroleum jelly sold by the company Aiglon) was added. 3. At 7 minutes, the high-molecular-weight S-EB-S (Kraton G 1651 sold by the company Kraton) and the antioxidant (Irganox 1010 sold by the company Ciba Specialty Chemicals) were added. The temperature of the mixture was then 113 C. 4. At 41 minutes, the tackifying resin (Escorez 5380 sold by the company Exxon Mobil Chemical) was added. The mixer was emptied at 60 minutes.

(17) The amounts (expressed as weight per 100 grams) of the various constituents of the elastomeric masses thus prepared are given in table 1.

b2. Production of Petroleum Jelly-Based Masses

Examples 13 to 18

(18) The petroleum jelly-based masses of examples 13 to 18 were prepared at 45 C. in a beaker according to the following process:

(19) The petroleum jelly (codex A petroleum jelly sold by the company Aiglon), the active substance (potassium sucrose octasulfate sold by the company Euticals or silver sulfadiazine from the company Argenol Bentley), as appropriate, the carboxymethylcellulose (CMC Blanose 7H4XF from the company Hercules) and, as appropriate, the copolymer (Sepinov EMT 10 sold by the company SEPPIC) were mixed manually.

(20) The amounts (expressed as weight per 100 grams) of the various constituents of these masses are given in table 2.

(21) TABLE-US-00001 TABLE 1 Kraton Kraton Codex A CMC Potassium Ondina G G Kraton D Irganox petroleum Blanose Luquasorb Escorez sucrose Silver Sepinov 917 1651 1654 1111K 1010 jelly 7H4XF 1003 5380 octasulfate sulfadiazine EMT10 Ex. 1 62.38 6 0.12 5 14 7.5 5 Ex. 2 67.38 6 0.12 5 14 7.5 Ex. 3 71.2 4.93 0.12 5 10 3.75 5 Ex. 4 76.2 4.93 0.12 5 10 3.75 Ex. 5 62.4 6 0.1 5 14 7.5 5 Ex. 6 67.4 6 0.1 5 14 7.5 Ex. 7 38.4 10 0.1 5 14 20 7.5 5 Ex. 8 43.4 10 0.1 5 14 20 7.5 Ex. 9 27.38 6 0.12 5 14 35 7.5 5 Ex. 10 32.38 6 0.12 5 14 35 7.5 Ex. 11 36.2 4.93 0.12 5 10 35 3.75 5 Ex. 12 41.2 4.93 0.12 5 10 35 3.75

(22) TABLE-US-00002 TABLE 2 Codex CMC Potassium A petroleum Blanose sucrose Silver Sepinov jelly 7H4XF octasulfate sulfadiazine EMT 10 Example 13 78 9.5 7.5 5 Example 14 83 9.5 7.5 Example 15 82.5 7.5 10 Example 16 92.5 7.5 Example 17 86.25 3.75 10 Example 18 96.25 3.75

c. Production of Dressings and Tested Products

(23) c.sub.1. Interface dressings constituted of a mesh coated with an elastomeric mass were produced using the abovementioned elastomeric masses of examples 1 to 4.

(24) More specifically, a mesh formed from a thermoset marquisette made of polyester (polyethylene terephthalate) yarns of 33 decitex in the warp and weft directions, having square mesh cells with an aperture of approximately 0.8 to 1 mm.sup.2 (mesh 555 sold by the company MDB Texinov) was used here.

(25) This mesh was coated with a layer of molten elastomeric mass at 135-145 C., and then the excess was removed by passing between two fixed rollers having a gap of 200 m therebetween. The strip thus obtained was cut and then complexed with a 23 m thick protective polyester film, on each of its sides, thus forming individual dressings packaged in impermeable pouches and sterilized under -radiation at 25 kGy.

(26) c.sub.2. Sheets of elastomeric masses of examples 5 to 12 were prepared between two 75 m sheets of siliconized polyester, by means of a heating press, the two plates of which were set at 95 C. The thickness of these sheets of elastomeric mass was calibrated by means of inserts having a thickness of 1150 m, so as to obtain sheets of, on average, 1 mm.

(27) c.sub.3. The petroleum jelly-based masses of examples 13 to 18 was partly coated onto a viscose 552 mesh (sold by the company MDB Texinov) and partly conserved in order to analyze the release of the active substance contained in this mass.

(28) c.sub.4. The interface dressings prepared using the elastomeric masses of examples 1 to 4 were heat-complexed with a 4.5 mm thick hydrophilic polyurethane foam, sold by the company Corpura B.V under the trade name Vivo MFC.03. The complex was placed between two hotplates under pressure at a temperature of approximately 100 C. A polyester fingerlift having a thickness of 50 m was applied to the side of the interface dressing. The complex dressings thus obtained were packaged individually in impermeable pouches and sterilized under -radiation at 25 kGy.

(29) The dressings thus obtained are hereinafter denoted examples 19 to 22 and are represented in table 3.

(30) TABLE-US-00003 TABLE 3 Example 19 Dressing of example 1 + polyurethane foam Example 20 Dressing of example 2 + polyurethane foam Example 21 Dressing of example 3 + polyurethane foam Example 22 Dressing of example 4 + polyurethane foam
Method of Measuring the Release of an Active Substance

(31) The ability of a copolymer of a salt of 2-methyl-2-[(1-oxo-2-propenyl)amino]-1-propanesulfonic acid and of 2-hydroxyethylpropenoate ester to promote the release of an active substance is illustrated by means of the following analysis methods:

(32) In the case of interface dressings, prepared from the masses of examples 1 to 4 and 13 to 18, samples of 25 cm.sup.2 of dressing (cut with a calibrated punch and precisely weighed) were introduced into an Erlenmeyer flask containing 10 ml of physiological saline solution. The glassware, hermetically sealed, was placed in an incubator at 37 C. for 24 h. The supernatant was removed and filtered. The amount of active substance was assayed by HPLC (high performance liquid chromatography) according to the methods described below.

(33) In the case of the interface dressings complexed with a foam, of examples 19 to 22, the liquid was completely absorbed by the device. In this case, the dressing was saturated with physiological saline solution in order to obtain approximately 10 ml of supernatant.

(34) In order to standardize the method, samples of 25 cm.sup.2 of absorbent dressing (cut with a calibrated punch and precisely weighed) were placed in an Erlenmeyer flask containing 25 ml of physiological saline solution. The glassware, hermetically sealed, was placed in an incubator at 37 C. for 24 h. The supernatant was removed and the amount of active substance was assayed by HPLC (high performance liquid chromatography) according to the methods described below.

(35) In the case of the masses in the form of sheets, of examples 5 to 12, samples of 25 cm.sup.2 of sheet (cut with a calibrated punch and precisely weighed) were placed in an Erlenmeyer flask containing 10 ml of physiological saline solution. The glassware, sealed hermetically, was placed in an incubator at 37 C. for 24 h. The supernatant was removed and filtered. The amount of active substance was assayed by HPLC (high performance liquid chromatography) according to the methods described below.

(36) In the case of the masses in the form of a paste/ointment, obtained using the masses of examples 13 to 18, 1000 mg of mass were spread out at the bottom of an Erlenmeyer flask containing 10 ml of physiological saline solution. The glassware, hermetically sealed, was placed in an incubator at 37 C. for 24 h. The supernatant was removed and filtered. The amount of active substance was assayed by HPLC (high performance liquid chromatography) according to the methods described below.

(37) Method for Assaying Potassium Sucrose Octasulfate

(38) The following conditions for assaying by high performance liquid chromatography (HPLC) were used:

(39) Reagents

(40) Ammonium sulfate, for example Normapur code 21 333 296 from Prolabo. HPLC-grade demineralized water. Potassium sucrose octasulfate. Orthophosphoric acid, for example Carlo Erba code 406002 or equivalent.
Chromatographic Conditions Waters Alliance 2695 HPLC. NH.sub.2 column. Eluent: aqueous solution of ammonium sulfate buffered at pH=3.00. Flow rate: 1 ml/min. Injected volume: 50 l. Column temperature=30 C. Detection: refractometry (T int=35 C.).
Preparation of the Standard Solutions for the Chromatographic Analysis

(41) A calibration range was prepared with 3 controls: 0.3 mg/ml-1 mg/ml-2.5 mg/ml.

(42) The detection threshold for the potassium sucrose octasulfate was 0.06 mg/ml. When no peak was detected, the result was increased by the detection threshold.

(43) Method for Assaying Silver Sulfadiazine

(44) The silver sulfadiazine was assayed by high performance liquid chromatography (HPLC), under the following conditions:

(45) Reagents

(46) HPLC-grade water. Orthophosphoric acid, for example Carlo Erba code 406002 or equivalent quality. Acetonitrile Silver sulfadiazine.
Chromatographic Conditions Flow rate: 1 ml/min. Column oven temperature: 30 C. Wavelength : 264 nm. Eluent phase: water/acetonitrile/orthophosphoric acid (respective volumes: 900/99/1).
Preparation of the Standard Solutions for the Chromatographic Analysis

(47) A calibration range was prepared with 2 controls: 0.4 mg/ml-2.5 mg/ml.

(48) The detection threshold for the silver sulfadiazine was 0.0006 mg/ml. When no peak was detected, the result was increased by the detection threshold.

(49) Assaying Method: Results Determination

(50) A calibration straight line was plotted using the calibration points, and the equation of the straight line y=ax+b (r.sup.2>0.999), in which
y=surface area under the peak
x=concentration of the standard (in mg/ml)
r.sup.2=determination coefficient,
was calculated. The content of potassium sucrose octasulfate or silver sulfadiazine (x) was calculated.

(51) The HPLC results are expressed in mg/ml.

(52) The percentage of release of the active substance is calculated according to the following formula:

(53) ${\mathrm{Content}}_{\%}=\frac{x.Math.V}{m.Math.C}$
in which:
content %=release of the active substance relative to the theoretical content in the dressing.
X=release of active substance in the physiological saline solution in mg/ml (HPLC datum).
V: volume of physiological saline solution introduced during the release study (10 ml or 20 ml for the absorbent dressings).
m=mass of the coating (mg).
C=active principle content of the coating (%).

(54) The results of the release measurements thus obtained are given in tables 4 to 7.

(55) TABLE-US-00004 TABLE 4 Release of the active substance in the interface dressings of examples 1 to 4 Example 1 Example 2 Example 3 Example 4 Release of the active 0.74 0.06 0.155 0.007 substance (mg/ml) Release of the active 28.40 2.63 13.5 0.65 substance (%)

(56) TABLE-US-00005 TABLE 5 Release of the active substance in sheets of elastomeric masses Ex. Ex. 5 Ex. 6 Ex. 7 Ex. 8 Ex. 9 10 Ex. 11 Ex. 12 Release 0.77 0.06 1.10 0.06 1.98 0.06 0.085 0.003 of the active substance (mg/ml) Release 15.38 1.21 19.56 1.14 10.07 0.31 0.91 0.03 of the active substance (%)

(57) TABLE-US-00006 TABLE 6 Release of the active substance in the interface dressings of examples 13 to 18 Ex. 13 Ex. 14 Ex. 15 Ex. 16 Ex. 17 Ex. 18 Release of 3.01 1.16 6.02 0.32 0.393 0.098 the active substance (mg/ml) Release of the 63.74 18.09 87.73 5.04 12.78 3.15 active substance (%)

(58) TABLE-US-00007 TABLE 7 Release of the active substance in the interface dressings complexed with foams, of examples 19 to 22 Ex. 19 Ex. 20 Ex. 21 Ex. 22 Release of the active 0.53 0.09 0.10 0.006 substance (mg/ml) Release of the active 50 9.89 17.97 1.02 substance (%)

(59) These results show that, although it is not a surfactant, such as polysorbate 80 (Montanox 80, sold by the company SEPPIC), a copolymer of a salt of 2-methyl-2-[(1-oxo-2-propenyl)amino]-1-propanesulfonic acid and of 2-hydroxyethylpropenoate ester allows release of the active substance. These results also show that, whatever the nature of the active substance (water-soluble or water-insoluble) is, the release nevertheless takes place.

(60) Comparative Study

(61) The ability of the abovementioned copolymer to release an active substance (such as potassium sucrose octasulfate or silver sulfadiazine) was measured in masses comprising at least one fatty substance, and compared with that obtained with a surfactant, in the case in point polysorbate 80 (Montanox 80 sold by the company SEPPIC).

(62) To this effect, elastomeric masses containing polysorbate 80 and an active substance (the potassium sucrose octasulfate sold by the company Euticals) were prepared according to the same process as for examples 1 to 8, other than the fact that the Sepinov EMT 10 copolymer was replaced with Montanox 80 sold by the company SEPPIC.

(63) The amounts (expressed by weight per 100 grams) of the various constituents of the masses thus prepared (examples 23 and 24) are given in table 8.

(64) Interface dressings constituted of a mesh coated with an elastomeric mass were produced using the masses thus prepared.

(65) More specifically, a mesh formed from a thermoset marquisette made of polyester (polyethylene terephthalate) yarns of 33 decitex in the warp and weft directions, having square mesh cells with an aperture of approximately 0.8 to 1 mm.sup.2 (mesh 555 sold by the company MDB Texinov) was used here.

(66) This mesh was coated with a layer of molten mass at 115 C., and then the excess was removed by passing between two fixed rollers having a gap of 200 m therebetween. The strip thus obtained was cut and then complexed with a protective polyester film 23 m thick, on each of its sides, thus forming individual dressings packaged in impermeable pouches and sterilized under -radiation at 25 kGy.

(67) TABLE-US-00008 TABLE 8 CMC Potassium Ondina Kraton G Irganox Vaseline Blanose sucrose Silver Montanox 917 1654 1010 Codex A 7H4XF octasulfate sulfadiazine 80 Example 23 62.38 6 0.12 5 14 7.5 5 Example 24 71.2 4.93 0.12 5 10 3.75 5
Comparison of the Ability to Release an Active Substance Between the Copolymer Used According to the Invention and a Surfactant of Polysorbate 80 Type

(68) The dressings of examples 1 and 3 (containing the Sepinov EMT 10 copolymer as releasing agent) and the dressings of examples 23 and 24 (containing Montanox 80 as releasing agent) were tested according to the method of measuring the release of an active substance from interface dressings described above.

(69) The results obtained are given in table 9.

(70) TABLE-US-00009 TABLE 9 Release of an active substance (expressed as mg/ml and as percentage) using the masses according to examples 1, 23, 3 and 24 Example 1 Example 23 Example 3 Example 24 Release of the 0.74 0.87 0.155 0.251 active substance (mg/ml) Release of the 28.4 32.94 13.5 19.6 active substance (%)

(71) As it can be seen, substantially the same release of the active substance is obtained, irrespective of its nature, with the Montanox 80 or the Sepinov EMT 10 copolymer.

(72) Demonstration of the Absence of Cytotoxicity with Respect to Fibroblasts of the Copolymer Used in the Context of the Invention

(73) In order to demonstrate this advantageous property, interface dressings were tested on fibroblast cultures according to the following method:

(74) Materials and Methods

(75) Cells Used:

(76) Type: pool of normal human dermal fibroblasts (NHDF) R9PF2 Culture: 37 C., 5% CO.sub.2
Culture Medium: DMEM (Dulbecco's Modified Eagle Medium, Invitrogen 21969035) 2 mM L-glutamine (Invitrogen 25030024) 50 UI/ml penicillin, 50 g/ml streptomycin (Invitrogen 15070063) 10% fetal calf serum (v/v, Invitrogen 10270098).
Products Tested:

(77) Dressings according to examples 1 and 23 were cut to the size of the wells and tested.

(78) Effects on Proliferation:

(79) The fibroblasts were seeded at confluence in a 12-well plate.

(80) Pieces of each dressing were cut to a size of 1.4 cm1.4 cm (i.e. 1.96 cm.sup.2), applied to the surface of the fibroblasts and held in place using a plug. A control without dressing but with a plug, and also a control without dressing and without plug were carried out.

(81) The cells were then incubated for 48 hours, 96 hours and 168 hours (7 days) at 37 C. and 5% CO.sub.2. For each incubation time, the metabolic activity was measured using a standard MTT test, which accounts for the mitochondrial dehydrogenases activity. Tritiated thymidine ([methyl-3H]-thymidine, Amersham TRK 686 2.5 Ci/ml final concentration) was added during the last 24 hours of incubation, and then the DNA of the cells of the cell layers was extracted and purified and the radioactivity incorporated into the DNA was counted using a scintillation counter.

(82) All experiments were carried out in triplicate. The raw counting data were transferred and processed using the Prism software (Graph Pad Software).

(83) The results obtained are expressed in counts per minute (cpm), and then as percentage relative to the control, according to the following formula:
%.sub.control=(cpm.sub.test/cpm.sub.control)100
in which:
cpm.sub.test: number of counts per minute obtained with the test
cpm.sub.control number of counts per minute obtained with the control.

(84) The results obtained are given in table 10.

(85) Photographs of the fibroblasts were taken at the end of the treatment after staining with MTT. These photographs are reproduced in FIG. 1.

(86) TABLE-US-00010 TABLE 10 Fibroblast viability (expressed as percentage) 48 h, 96 h, and 168 h after treatment Fibroblast Fibroblast Fibroblast viability at viability at viability at 48 hours (%) 96 hours (%) 168 hours (%) Control 100 100 100 Control without 98 103 107 plug Dressing according 128 140 140 to example 1 Dressing according 70 68 57 to example 23

(87) As shown from the results of table 10, the use of the Sepinov EMT 10 copolymer in dressings, in amounts equivalent to a surfactant such as Montanox 80, makes it possible to release an active substance in equivalent proportions and exhibits a further advantage, which is that of promoting fibroblast proliferation.

(88) FIG. 1 shows the effect of the dressings of examples 1 and 23 on cell viability after direct contact with the fibroblasts after 48 h, 96 h and 168 h. This observation of the morphology of the fibroblasts after removal of the dressings and staining with MTT was visualized by optical microscopy and the taking of representative photographs (10 objective) and confirms the beneficial effect of the Sepinov EMT 10 copolymer on fibroblast proliferation in comparison with Montanox 80.