New cryogenic composition

Abstract

Novel Cryogenic Composition The present invention relates to a novel cryogenic composition for use in heat treatment devices, as well as a method for its preparation. The invention also relates to a heat treatment device, and more particularly a medical device used to cool a part of the human or animal body, especially after trauma, inflammation, or surgery. The invention has applications in the therapeutic and / or medical field, but also in other fields such as cooling or maintaining the low temperature of food or beverages.

Description

Title of the invention: Novel cryogenic composition technical field

[0001] The present invention relates to a novel cryogenic composition for use in heat treatment devices, as well as a method for its preparation. The invention also relates to a heat treatment device, and more particularly to a medical device used to cool a part of the human or animal body, especially after trauma, inflammation, or surgery. The invention therefore has applications in the therapeutic and / or medical field, but also in other fields such as, for example, cooling or maintaining food or beverages at low temperatures. Prior art

[0002] Cryotherapy, or cold therapy, emerged in the 1970s and is now widely used in the medical field to heal damaged tissues, promote healing, and relieve bodily pain such as sprains, tendinitis, and muscle strains. Its principle consists of exposing a part of the human or animal body to cold to induce the secretion of endorphins, which has the effect of producing analgesia, and thus lowering the pain threshold. Cryotherapy is therefore used after post-traumatic or post-surgical procedures for its hemolytic and anti-edematous action.

[0003] Cryotherapy uses different sources of cold: - Nitrogen-based devices derived from the instantaneous gasification of liquid nitrogen, this technique involving the use of heavy and bulky equipment, and therefore not very maneuverable. - Water-based heat treatment devices. Water is one of the materials that best retains cold. However, at temperatures below 0°C, water turns into ice and presents certain drawbacks due to its solid structure, which is difficult to conform to an anatomical structure, and whose very low temperature causes tissue damage. - Devices based on antifreeze compositions that do not undergo a phase change when frozen at -25°C. These compositions, available in bead or gel form, produce a very unstable cold, making them unsuitable for cryotherapy. Devices using these compositions exhibit a surface temperature upon thawing that can be as low as -5°C for gels and beads. - Phase-change devices such as those described in the patent EP 1 011 558. This patent describes compositions comprising water, an acrylic polymer absorbent, and a humectant. Upon freezing, some of the water contained within the absorbent's network is released and changes phase, transforming into ice crystals. Upon warming, the water re-enters the absorbent network. These compositions remain flexible and conformable. However, they are not very resistant to repeated freeze / thaw cycles and tend to become less flexible with each cycle, making them uncomfortable and less effective in use. Furthermore, these compositions have the disadvantage of requiring a container with a semi-permeable, watertight, and air-permeable zone, which complicates the device.During defrosting, the device also exhibits a surface temperature below 0°C for an extended period, thus reducing its usability, as it is necessary to wait for the temperature to stabilize above 0°C or to place an insulating layer between the device and the skin before use.

[0004] WO2017 / 125687 describes cryogenic compositions comprising a hy compound A liquid drophobe with a freezing point below 0°C, in which superabsorbent polymer granules loaded with water and a humectant are immersed. The liquid phase of these compositions is not an emulsion. These cryogenic compositions exhibit good cold kinetics, but insufficient performance in terms of flexibility (aggregation / degradation of the superabsorbent polymer granules) beyond a certain number of freeze / thaw cycles.

[0005] In this context, the present invention aims to overcome the drawbacks of prior art devices by providing a heat treatment device containing a novel cryogenic composition that does not deteriorate during freeze / thaw cycles (no aggregation / degradation of the cryogenic composition over time). The device of the invention has the advantage of high durability and can thus be reused several times (more than sixty times without deterioration). A few minutes after thawing, the device of the invention has a surface temperature ideally between 7 and 10°C, remains stable for at least 70 minutes, and up to 120 minutes. Furthermore, the heat treatment device remains perfectly flexible after freezing.

[0006] The inventors discovered that it was possible to achieve these performance levels using a cryogenic composition comprising a significant amount of superabsorbent polymer. They observed that the cryogenic composition of the invention is more stable (resistant to a greater number of freeze / thaw cycles) and more malleable and flexible after freezing. Unlike prior art compositions, the cryogenic composition of the invention allows for greater absorption. homogeneous superabsorbent polymer granules, and thus improves the stability and flexibility of the heat treatment device of the invention.

[0007] Another advantage of the invention is the preparation time of the cryogenic composition, which is significantly shortened compared to prior art processes, the hydration time of the superabsorbent polymer granules being considerably reduced (divided by two) in the process of the invention, thus leading to a significant time saving.

[0008] Thus, according to a first aspect, the present invention relates to a cryogenic composition comprising: (a) superabsorbent polymer granules impregnated with a liquid phase, said liquid phase comprising: (b) at least one hydrophobic compound selected from neopentylene glycol diheptanoate, isopropyl sebacate, isodecyl neopentanoate, isostearyl isostearate, and mixtures thereof, (c) at least one humectant, (d) possibly at least one preservative, and (e) water, said superabsorbent polymer granules (a) representing more than 6% by weight relative to the total weight of the cryogenic composition.

[0009] For the purposes of this invention, a "superabsorbent polymer" is defined as a polymer that, in its dry state, is capable of spontaneously impregnating / absorbing at least 20 times its own weight of aqueous fluid, particularly water. This polymer has a high capacity for absorbing and retaining water and aqueous fluids. After absorption of the aqueous liquid, the polymer granules thus impregnated with aqueous fluid remain insoluble in the aqueous fluid and thus retain their individualized state. Examples of superabsorbent polymers are described in "Absorbent Polymer Technology, Studies in Polymer Science 8" by L. Brannon-Pappas and R. Harland, Elsevier, 1990.

[0010] Among the superabsorbent polymers (a) that can be used in the context of the present invention, mention may be made of crosslinked sodium or potassium polyacrylates, polyacrylamides, ethylene-maleic anhydride copolymers, vinyl alcohol copolymers, crosslinked polyethylene oxide, starch-based polymers, gum-based polymers and cellulose derivatives, pectins, alginates, agar-agar (or agarose), polyethylene amines, polyvinyl amines, and mixtures thereof. The superabsorbent polymer (a) is preferably a crosslinked acrylic homo- or copolymer, and even more preferably a crosslinked sodium or potassium acrylic homo- or copolymer.

[0011] The superabsorbent polymer (a) is advantageously present in the composition cryogenic of the invention in an amount from 7 to 25%, preferably from 7 to 20%, and more preferably from 8 to 15%, relative to the total weight of the cryogenic composition.

[0012] Advantageously, the superabsorbent polymer granules (a) of the invention are in the form of spherical beads having a diameter of 1 to 6 mm when dehydrated. According to a more preferred embodiment, the spherical beads of superabsorbent polymer (a) are sodium or potassium polyacrylate beads, and even more preferably potassium polyacrylate beads, preferably having a diameter of 1 to 3 mm when dehydrated. These spherical beads can absorb at least 40 times their mass, this characteristic being defined under normal temperature (20°C) and pressure (100,000 Pa) conditions and for water. Once hydrated, the spherical beads of superabsorbent polymer (a) swell and form soft beads.

[0013] In the cryogenic composition of the invention, the superabsorbent polymer granules (a) preferably represent at least 7% by weight, and more preferably at least 8% by weight, relative to the total weight of the cryogenic composition. In a particularly preferred embodiment, the superabsorbent polymer granules (a) represent at least 9% by weight, and even more preferably at least 10% by weight, relative to the total weight of the cryogenic composition.

[0014] In the cryogenic composition of the invention, the hydrophobic compound (b) advantageously has a freezing point below -7°C, preferably below -10°C, more preferably below -15°C, and even more preferably below -20°C. It advantageously has a high molecular weight, ranging from 200 to 700 g / mol. The hydrophobic compound (b) is in liquid form. It is preferably selected from neopentylene glycol diheptanoate, isopropyl sebacate, isodecyl neopentylene glycol neopentylene glycol, isostearyl isostearate, and mixtures thereof, and more preferably neopentylene glycol diheptanoate.These hydrophobic compounds (b) are marketed for example by the company STEARINERIE DUBOIS under the references DUB DNPG (neopentylene glycol diheptanoate, freezing point: -55°C), DUB DIS (isopropyl sebacate, freezing point: -20°C), DUB VCI 10 (isodecyl neopentanoate, freezing point: -35°C), DUB ISIS (isostearyl isostearate), or by the company INTERCHIMIE.

[0015] The hydrophobic compound(s) (b) preferably represent 0.1 to 8%, more preferably 0.1 to 6%, and even more preferably 0.1 to 4%, relative to the total weight of the cryogenic composition.

[0016] In the cryogenic composition of the invention, the humectant (c) can be chosen from glycerol, sorbitol, polyethylene glycol, (di)propylene glycol, the Polypropylene glycol, 1,5-pentanediol, propylene glycol, butylene glycol, diethylene glycol, paraffin oil and mixtures thereof, preferably glycerol, (di)propylene glycol, polypropylene glycol and mixtures thereof, and even more preferably (di)propylene glycol, polypropylene glycol and mixtures thereof. Dipropylene glycol is the most preferred humectant (d).

[0017] The humectant agent (c) preferably represents 1 to 20%, more preferably 5 to 20%, and even more preferably 5 to 15%, relative to the total weight of the cryogenic composition.

[0018] When present, the preservative (d) is advantageously selected from isothiazolinones such as 2-methyl-2H-isothiazol-3-one, 5-chloro-2-methyl-4-isothiazolin-3-one, 2-methyl-4-isothiazolin-3-one, and mixtures thereof. Preferably, the preservative (d) is 2-methyl-2H-isothiazol-3-one, marketed, for example, under the name Microcare® MT (manufacturer THOR). The preservative (d) is advantageously free of formaldehyde compounds.

[0019] When present, the preservative agent (d) preferably represents 0.05 to 5%, more preferably 0.05 to 4%, and even more preferably 0.1 to 3%, relative to the total weight of the cryogenic composition.

[0020] The liquid phase of the cryogenic composition of the invention is advantageously in the form of an oil-in-water emulsion. In this oil-in-water emulsion, the oil phase is preferably made up of the hydrophobic compound(s) (b), and the aqueous phase of the humectant(s) (c), optionally of the preservative(s) (d), and water (e).

[0021] According to a preferred embodiment, the cryogenic composition of the invention comprises: (a) 7 to 25%, preferably 7 to 20%, and more preferably 8 to 15%, by weight of superabsorbent polymer granules, (b) from 0.1 to 8%, preferably from 0.1 to 6%, and more preferably from 0.1 to 4%, by weight of at least one hydrophobic compound selected from neopentylene glycol diheptanoate, isopropyl sebacate, isodecyl neopentanoate, isostearyl isostearate, and mixtures thereof, (c) 1 to 20%, preferably 5 to 20%, and more preferably 5 to 15%, by weight of at least one humectant, (d) 0.05 to 5%, preferably 0.05 to 4%, and more preferably 0.1 to 3%, by weight of at least one preservative, (e) from 60 to 90%, preferably from 65 to 85%, and more preferably from 70 to 85%, by weight of water, said percentages being expressed as percentages by weight relative to the total weight of the cryogenic composition, and the total weight of the cryogenic composition re- showing 100%.

[0022] Another object relates to a method for preparing a cryogenic composition according to the invention comprising the following steps: (i) under agitation, preparation of an oil-in-water emulsion by adding at least one hydrophobic compound (b) to an aqueous mixture based on at least one humectant (c), optionally at least one preservative (d), and water (e), (ii) addition of superabsorbent polymer granules (a) into the oil-in-water emulsion obtained at the end of step (i), (iii) impregnation of the oil-in-water emulsion obtained at the end of step (ii) with the superabsorbent polymer granules (a), by allowing said superabsorbent polymer granules (a) to stand at room temperature, preferably until they reach a size between two and four times their initial size.

[0023] Step (i) of preparing the oil-in-water emulsion is carried out under agitation, preferably at a speed ranging from 5000 to 15000 rpm, and more preferably from 8000 to 12000 rpm, for a duration ranging preferably from 30 seconds to 5 minutes, and more preferably from 30 seconds to 3 minutes. Agitation can be carried out using a Dynamic SMX 800 Turbo mixer.

[0024] Step (iii) of impregnating the oil-in-water emulsion obtained at the end of step (ii) with the superabsorbent polymer granules (a) is preferably carried out for a period of 1 to 5 hours, and more preferably for a period of 1 to 2 hours.

[0025] A heat treatment device comprising a sealed container, inside which is contained a cryogenic composition according to the invention, is also part of the invention. The container is advantageously made of a flexible material such as polyvinyl chloride (PVC), polychloroprene (neoprene), polytetrafluoroethylene (PTFE), or polyethylene (PE), and preferably polyethylene (PE). In an advantageous embodiment, the container is a multi-layered material comprising at least one layer of polyethylene (PE). The device is preferably a sealed and flexible medical pouch, which can be applied to a part of the human or animal body, for example, to reduce hematomas, edema, or to relieve pain.

[0026] The heat treatment device of the invention can be obtained by simply filling a sealed container, preferably a medical bag, with a cryogenic composition according to the invention. The cryogenic composition of the invention is preferably stirred manually before being used to fill the sealed container. In practice, the cryogenic composition is generally stored in drums that can be inverted once or twice before use (manual stirring) to homogenize the cryogenic composition before use.

[0027] The invention therefore relates mainly to a medical device selected from a face mask, a splint for the shoulder, elbow, ankle, knee, hip or wrist, and any support comprising a waterproof and flexible medical pouch according to the invention.

[0028] The cryogenic composition of the invention, or the heat treatment device of the invention, can be used to cool a part of the human or animal body, preferably after trauma, inflammation, or surgery. The temperature can be visually controlled using a thermochromic pigment, previously added to the cryogenic composition of the invention. It can also be contained within the material of the container. This pigment can be a thermochromic pigment such as those marketed by OliKrom.

[0029] The heat treatment device of the invention can also be used for non-medical applications, such as lowering or maintaining the temperature of foodstuffs or beverages like wine, or to promote their preservation, or for transporting heat-sensitive articles in cold environments. In this case, the temperature can be visually monitored using a thermochromic pigment as described above.

[0030] The heat treatment device of the invention can be used in a heat treatment process to lower the temperature of a part of the human or animal body or to lower the temperature of foodstuffs or beverages, said process comprising the following steps: (i') freezing a device according to the invention at a temperature below 0°C, and preferably at a temperature between -20°C and -30°C, for a period of 2 to 4 hours, (ii') manual kneading of the device obtained at the end of step (i'), (iii') application of the device obtained at the end of step (ii') on a part of the human or animal body, with or without the aid of a medical device according to the invention, preferably for a period of between 30 minutes and 120 minutes.

[0031] In addition to the foregoing provisions, the invention also includes other provisions which will become apparent from the following supplementary description, which relates to examples highlighting the advantageous properties of the cryogenic composition of the invention. Examples:

[0032] Example 1:

[0033] A cryogenic composition according to the invention was prepared by mixing 11400 g of water with 1620 g of dipropylene glycol (supplier: INTERCHIMIE) and 30 g of 2-methyl-2H-isothiazol-3-one (Microcare® MT, THOR), under manual stirring. 450 g of neopentylene glycol diheptanoate (DUB DPNG from STEARINERIE DUBOIS) were added to the water, dipropylene glycol and 2-methyl-2H-isothiazol-3-one was added, and the mixture was then stirred at 11,000 rpm for 1 minute and 30 seconds using a Dynamic SMX 800 Turbo mixer to form an oil-in-water emulsion. 1500 g of 1.5 mm diameter potassium polyacrylate beads (supplier: Shanghai Chuangshi Medical Technology Group Co., Ltd.) were then added to the resulting emulsion. The emulsion was left to stand at room temperature for 1.5 hours (impregnation step with the polymer beads) until the potassium polyacrylate beads reached an average diameter of 4 mm. 390 g of the resulting mixture was poured into a 295 mm diameter polyethylene (PE) bag. The bag was then sealed and placed in a freezer at -20°C for 3 hours. During freezing, some of the water contained in the polymer beads changed phase and transformed into small ice crystals that looked like snow.

[0034] Upon removal from the freezer, the sample temperature was measured every minute for 120 minutes under a compression of 14 g / cm², using a TESTO 175 T2 temperature recorder with a CTN-type probe. Measurements were taken every minute at the interface between the frozen bag and a 2 cm thick water bag at 20°C. The bag temperature remained between 7 and 10°C for 71 minutes. The bag is therefore suitable for cryotherapy treatment for 71 minutes.

[0035] The aging of the cryogenic composition was also evaluated by measuring the number of freeze / thaw cycles. Aging becomes noticeable when the polymer beads begin to clump together, leading to a decrease in the flexibility of the frozen pouch. With the cryogenic composition of Example 1, the pouch remained homogeneous (no degradation of the polymer beads) and flexible until the 60th freeze / thaw cycle. Measurements were stopped at this point.

[0036] Counterexample 1:

[0037] A cryogenic composition representative of the prior art WO2017 / 125687A1 was prepared by mixing 14,000 g of water with 1,190 g of dipropylene glycol (supplier: INTERCHIMIE), under manual stirring. 350 g of potassium polyacrylate beads with a diameter of 1.5 mm (supplier: Shanghai Chuangshi Medical Technology Group Co., Ltd.) were added to the water and dipropylene glycol mixture. The mixture was left to stand at room temperature for 3 hours (polymer bead impregnation step), until the potassium polyacrylate beads reached an average diameter of 5.5 mm. 56 g of neopentylene glycol diheptanoate (DUB DPNG from STEARINERIE DUBOIS) were poured into a polyethylene (PE) bag with a diameter of 295 mm. The water-based mixture, Dipropylene glycol and potassium polyacrylate beads, previously prepared, were also added to the PE bag. The bag was then sealed and placed in a freezer at -20°C for 3 hours. During freezing, some of the water contained in the polymer beads changed phase and transformed into small ice crystals resembling snow.

[0038] As in Example 1, the sample temperature was measured every minute for 120 minutes under a compression of 14 g.cm², using a TESTO 175 T2 temperature recorder with an NTC probe. Measurements were taken every minute at the interface between the frozen bag and a 2 cm thick water bag at 20°C. The bag temperature remained between 7.5 and 10°C for 70 minutes.

[0039] As with Example 1, the aging of the cryogenic composition of Counter-Example 1 was evaluated by measuring the number of freeze / thaw cycles. Aging becomes visible when the polymer beads begin to aggregate, leading to a decrease in the flexibility of the frozen pouch. The pouch deteriorated from the 3rd freeze / thaw cycle (aggregation of the polymer beads), then lost its homogeneity and flexibility and was no longer usable from the 25th freeze / thaw cycle.

[0040] The examples above show that the cryogenic composition of Example 1 (invention) significantly improves the flexibility of the frozen pouch while maintaining the integrity of the polymer beads (no aggregation / degradation of the polymer beads) beyond 60 freeze / thaw cycles. Another advantage of the cryogenic composition of the invention is the reduced impregnation time of the polymer beads, which is lowered to 1.5 hours instead of 3 hours (time savings during the preparation of the cryogenic composition of the invention).

Claims

Demands

1. Cryogenic composition comprising: (a) superabsorbent polymer granules impregnated with a liquid phase, said liquid phase comprising: (b) at least one hydrophobic compound being selected from neopentylene glycol diheptanoate, isopropyl sebacate, isodecyl neopentanoate, isostearyl isostearate, and mixtures thereof, and preferably neopentylene glycol diheptanoate, (c) at least one humectant, (d) optionally at least one preservative, and (e) water, characterized in that said superabsorbent polymer granules (a) represent more than 6% by weight, preferably at least 7% by weight, and more preferably at least 8% by weight, relative to the total weight of the cryogenic composition.

2. A cryogenic composition according to claim 1 characterized in that it comprises: (a) 7 to 25%, preferably 7 to 20%, and more preferably 8 to 15%, by weight, of superabsorbent polymer granules, (b) 0.1 to 8%, preferably 0.1 to 6%, and more preferably 0.1 to 4%, by weight, of at least one hydrophobic compound selected from neopentylene glycol diheptanoate, isopropyl sebacate, isodecyl neopentanoate, isostearyl isostearate, and mixtures thereof, and preferably neopentylene glycol diheptanoate, (c) 1 to 20%, preferably 5 to 20%, and more preferably 5 to 15%, by weight, of at least one humectant, (d) 0.05 to 5%, preferably 0.05 to 4%, and more preferably 0.1 to 3%, by weight of at least one preservative, (e) 60 to 90%, preferably 65 to 85%, and more preferably 70 to 85%, by weight of water,said percentages being expressed as percentages by weight relative to the total weight of the cryogenic composition, and the total weight of the cryogenic composition representing 100%.

3. Cryogenic composition according to claim 1 or claim 2, characterized in that the superabsorbent polymer of the granules (a) is selected from crosslinked sodium or potassium polyacrylates, polyacrylamides, ethylene anhydride-based copolymers maleic, vinyl alcohol copolymers, crosslinked polyethylene oxide, starch-based polymers, gum and cellulosic derivatives, pectins, alginates, agar-agar (or agarose), polyethylene amines, polyvinyl amines, and mixtures thereof.

4. Cryogenic composition according to any one of claims 1 to 3, characterized in that said superabsorbent polymer granules (a) are in the form of spherical beads having a diameter of 1 to 6 mm when dehydrated, said spherical beads being able to absorb at least 40 times their mass.

5. Cryogenic composition according to claim 4, characterized in that said superabsorbent polymer granules (a) are sodium or potassium polyacrylate beads, or a mixture thereof, advantageously potassium polyacrylate, having a diameter of 1 to 3 mm when dehydrated.

6. Cryogenic composition according to any one of claims 1 to 5, characterized in that the humectant (c) is selected from glycerol, sorbitol, polyethylene glycol, (di)propylene glycol, polypropylene glycol, 1,5-pentanediol, propylene glycol, butylene glycol, diethylene glycol, paraffin oil, and mixtures thereof, preferably from glycerol, (di)propylene glycol, polypropylene glycol and mixtures thereof, more preferably from (di)propylene glycol, polypropylene glycol and mixtures thereof, and even more preferably from dipropylene glycol.

7. Cryogenic composition according to any one of claims 1 to 6, characterized in that the preservative agent (d) is selected from isothia-zolinones such as 2-methyl-2H-isothiazol-3-one, 5-chloro-2-methyl-4-isothiazolin-3-one, 2-methyl-4-isothiazolin-3-one, and mixtures thereof, and preferably 2-methyl-2H-isothiazol-3-one.

8. A method for preparing a cryogenic composition as defined according to any one of claims 1 to 7, characterized in that it comprises the following steps: (i) under stirring, preparation of an oil-in-water emulsion by adding at least one hydrophobic compound (b) to an aqueous mixture based on at least one humectant (c), optionally at least one preservative (d), and water (e), (ii) addition of superabsorbent polymer granules (a) to the oil-in-water emulsion obtained at the end of step (i), (iii) impregnation of the oil-in-water emulsion obtained at the end of step (ii) with the superabsorbent polymer granules (a), by allowing said superabsorbent polymer granules (a) to stand at room temperature, preferably until they reach a size between two and four times their initial size.

9. A process according to claim 8, characterized in that step (iii) of impregnating the oil-in-water emulsion obtained at the end of step (ii) with the superabsorbent polymer granules (a) is carried out for a period of 1 to 5 hours, and preferably for a period of 1 to 2 hours.

10. Heat treatment device, characterized in that it comprises a sealed container, inside which is contained a cryogenic composition as defined according to any one of claims 1 to 7.

11. Device according to claim 10, characterized in that said container is a leak-proof and flexible medical pouch made of a material selected from polyvinyl chloride (PVC), polychloroprene (neoprene), polytetrafluoroethylene (PTFE) or polyethylene (PE), and preferably of a multilayer material comprising at least one layer of polyethylene (PE).

12. Medical device selected from a face mask, a splint for the shoulder, elbow, ankle, knee, hip or wrist, and any support comprising a leak-proof and flexible medical pouch as defined in claim 11.

13. Use of a cryogenic composition as defined in any one of claims 1 to 7, or of a heat treatment device according to claim 10, for lowering or maintaining the temperature of foodstuffs or beverages, or for promoting their preservation, or for the transport in a cold environment of heat-sensitive articles.