SACCHARIDE-BASED COMPOSITION FOR PROVIDING THERMAL INSULATION AND METHOD OF USE THEREOF

Abstract

A multi-layered composition for externally coating glass and ceramic substrates to provide thermal insulation and resistance of the substrate itself, and any further substances enclosed in the substrate in the case where the substrate is an open or enclosed container. Also provided are methods of manufacture and application for the disclosed composition.

Claims

1. A substrate coated with a multi-layered composition, wherein the multi-layered composition comprises: (a) a modification layer disposed on a surface of the substrate, said modification layer comprising at least one inorganic and/or organic compound capable of binding free hydroxyl groups; (b) at least one inner layer disposed on said modification layer, said at least one inner layer comprising: (i) a first layer comprising at least one monosaccharide or polysaccharide optionally substituted with one or more sterol groups; and (ii) optionally, a second layer comprising at least one inorganic oxide; and (c) a least one outer layer disposed on said inner layer, said at least one outer layer comprising a monomer or polymer of a hydrocarbon, anhydride, acrylic, urethane, derivatives thereof and combinations thereof.

2. The substrate of claim 1, wherein the substrate has free hydroxyl groups on a surface thereof.

3. The substrate of claim 2, wherein the substrate is glass or ceramic.

4. The substrate of claim 1, wherein the substrate is shaped as an open or closed container, such that the multi-layered composition is disposed on an external surface of the open or closed container.

5. The substrate of claim 1, where the multi-layered composition comprises 1, 2, 3, or 4 inner layers.

6. The substrate of claim 1, wherein the multi-layered composition comprises one modification layer, one inner layer comprising at least one monosaccharide or polysaccharide substituted with a sterol group, and an optional outer layer.

7. The substrate of claim 1, wherein the modification layer comprises TiCl.sub.4.

8. The substrate of claim 7, wherein the modification layer further comprises at least one inorganic oxide selected from the group consisting of TiO.sub.2, SiO.sub.2, InSnO.sub.2, and ZnO.

9. The substrate of claim 1 wherein the optional second layer of the inner layer comprises at least one inorganic oxide selected from the group consisting of TiO.sub.2, SiO.sub.2, InSnO.sub.2, and ZnO.

10. The substrate of claim 9, wherein the inorganic oxide is TiO.sub.2.

11. The substrate of claim 1 wherein said organic compound is siloxane.

12. The substrate of claim 1, wherein the first layer of the inner layer comprises a monosaccharide or polysaccharide substituted with one or more sterol groups selected from the group consisting of cholesterol, ergosterol, cortisol and combinations thereof.

13. The substrate of claim 1, wherein the first layer of the inner layer comprises a pullulan or cellulose optionally substituted with one or more sterol groups.

14. The substrate of claim 1, wherein the first layer of the inner layer comprises pullulan substituted with cholesterol or cellulose substituted with cholesterol.

15. The substrate of claim 1, wherein the at least one outer layer comprises polyurethane, polyvinyl, polylactic acid, or polyethylene, or a mixture thereof.

16. The substrate of claim 15, wherein the at least one outer layer comprises polyurethane.

17. The substrate of claim 15, wherein the polyurethane is a substituted branched poylurethane.

18. The substrate of claim 17, wherein the substituted branch polyurethane is a branched polyurethane substituted with a benzothiazole.

19. The substrate of claim 18 wherein the branched polyurethane substituted with a benzothiazole has a substitution degree of from about 0% to about 10%.

20. The substrate of claim 19 wherein the substitution degree is 3%.

21. A coated substrate, coated with a multi-layered composition selected from the group consisting of: (a) substrate-TiCl.sub.4-(TiO.sub.2).sub.nTiCl.sub.4-(Cellulose).sub.m-R; (b) substrate-TiCl.sub.4-(TiO.sub.2).sub.nTiCl.sub.4-(pullulan).sub.x-R; and (c) substrate-TiCl.sub.4-(TiO.sub.2).sub.nTiCl.sub.4-(Cellulose).sub.m-(TiO.sub.2).sub.y-(pullulan).sub.x-R wherein: n, m, x, and y represent a number of coatings of each layer, and each of n, m, x, and y is independently an integer equal to or greater than 1; and R is an outer layer, wherein the outer layer comprises polyurethane, polyvinyl, polylactic acid, or polyethylene, or a mixture thereof.

22. A method of preparing the substrate of claim 1, the method comprising: (a) coating the substrate with a composition comprising at least one inorganic and/or organic compound capable of at least one of i) binding free hydroxyl groups; ii) provide anionic functional groups; to form the modification layer; (b) coating the substrate having the modification layer formed in step (a) with a composition comprising at least one monosaccharide or polysaccharide optionally substituted with one or more sterol groups to form the inner layer, optionally followed by a layer of TiO.sub.2 wherein either or both steps (a) and (b) is repeated one or more times; and (c) coating the substrate formed in step (b) with a composition comprising a monomer or polymer of a hydrocarbon, anhydride, acrylic, urethane and combinations thereof to form the at least one outer layer, thereby obtaining the substrate coated with a multi-layered composition.

23. A method of improving thermal insulation or thermal resistance of a substrate, the method comprising providing a substrate coated with a multi-layered composition according to claim 1.

24. The method of claim 22, wherein the substrate is shaped as an open or closed container such that the multi-layered composition is disposed on an external surface of the open or closed container.

25. A method of improving thermal insulation or thermal resistance of a substrate, having free hydroxyl groups on a surface thereof, the method comprising coating a substrate with a multi-layered composition comprising: (a) coating the substrate with a composition comprising at least one inorganic and/or organic compound capable of binding free hydroxyl groups of said substrate to form a modification layer disposed on the substrate; (b) coating the substrate having the modification layer formed in step (a) with a composition comprising at least one monosaccharide or polysaccharide optionally substituted with one or more sterol groups optionally followed by a layer comprising TiO.sub.2 to form an inner layer, wherein either or both steps (a) and (b) is repeated one or more times; and (c) coating the substrate formed in step (b) with a composition comprising a monomer or polymer of a hydrocarbon, anhydride, acrylic, urethane, derivative thereof and combinations thereof to form an outer layer.

26. The method of claim 25, wherein the substrate is shaped as open or closed container, such that the multi-layered composition is disposed on an external surface of the open or closed container.

27. A method of improving thermal insulation or thermal resistance of a substrate, the method comprising providing a substrate coated with a multi-layered composition according to claim 20.

28. The method of claim 27, wherein the substrate is shaped as open or closed container, such that the multi-layered composition is disposed on an external surface of the open or closed container.

29. The substrate of claim 1, wherein the inner layer has a thickness of about 3 m to 1000 m.

30. The substrate of claim 1, wherein the inner layer has a thickness of about 200 m to 600 m.

31. The substrate of claim 1 wherein the outer layer has a thickness of about 1-40 m.

32. The substrate of claim 1 wherein the outer layer has a thickness of about 1-10 m.

33. A composition for coating an exterior surface of a substrate, said composition providing thermal insulation; said composition comprising: (a) a modification layer disposed on a surface of the substrate, said modification layer comprising at least one inorganic and/or organic compound capable of binding free hydroxyl groups; (b) at least one inner layer disposed on said modification layer, said at least one inner layer comprising: (iii) a first layer comprising a monosaccharide or polysaccharide optionally substituted with one or more sterol groups; and (iv) optionally, a second layer comprising at least one inorganic oxide; and (c) at least one outer layer disposed on said inner layer, said at least one outer layer comprising a monomer or polymer of a hydrocarbon, anhydride, acrylic, urethane, derivatives thereof and combinations thereof; wherein said substrate exterior surface of said substrate has at least one hydroxyl group present on the exterior surface thereof.

34. The composition of claim 33, where the composition comprises 1, 2, 3, or 4 inner layers.

35. The composition of claim 33, wherein the composition comprises one modification layer, one inner layer comprising at least one monosaccharide or polysaccharide substituted with a sterol group, and an optional outer layer.

36. The composition of claim 33, wherein the modification layer comprises TiCl.sub.4.

37. The composition of claim 33, wherein the modification layer further comprises at least one inorganic oxide selected from the group consisting of TiO2, SiO2, InSnO2, and ZnO.

38. The composition of claim 33, wherein the optional second layer of the inner layer comprises at least one inorganic oxide selected from the group consisting of TiO2, SiO2, InSnO2, and ZnO.

39. The composition of claim 33, wherein the inorganic oxide is TiO2.

40. The composition of claim 33 wherein said organic compound is siloxane.

41. The composition of claim 33, wherein the first layer of the inner layer comprises a monosaccharide or polysaccharide substituted with one or more sterol groups selected from the group consisting of cholesterol, ergosterol, cortisol and combinations thereof.

42. The composition of claim 33, wherein the first layer of the inner layer comprises a pullulan or cellulose optionally substituted with one or more sterol groups.

43. The composition of claim 33, wherein the first layer of the inner layer comprises pullulan substituted with cholesterol or cellulose substituted with cholesterol.

44. The composition of claim 33, wherein the at least one outer layer comprises polyurethane, polyvinyl, polylactic acid, or polyethylene, or a mixture thereof.

45. The composition of claim 33, wherein the at least one outer layer comprises polyurethane.

46. The composition of claim 45, wherein the polyurethane is a substituted branched polyurethane.

47. The composition of claim 46, wherein the substituted branch polyurethane is a branched polyurethane substituted with a benzothiazole.

48. The composition of claim 47, wherein the branched polyurethane substituted with a benzothiazole has a substitution degree of from about 0% to about 10%.

49. The composition of claim 48 wherein the substitution degree is 3%.

50. The substrate of claim 1 wherein the polysaccharide has a degree of sterol substitution from 0-30%.

51. The substrate of claim 1 wherein the polysaccharide has a degree of sterol substitution from 1-5%.

52. The coated substrate of claim 21 wherein the polysaccharide has a degree of sterol substitution from 0-30%.

53. The coated substrate of claim 21 wherein the polysaccharide has a degree of sterol substitution from 1-5%.

54. The method of claim 22, wherein the polysaccharide has a degree of sterol substitution from 0-30%.

55. The method of claim 22, wherein the polysaccharide has a degree of sterol substitution of from 1-5%.

56. The composition of claim 33, wherein the polysaccharide has a degree of sterol substitution from 0-30%.

57. The composition of claim 33, wherein the polysaccharide has a degree of sterol substitution of from 1-5%.

Description

BRIEF DESCRIPTION OF THE DRAWINGS

[0082] The disclosure, together with additional objects, features, advantages and aspects thereof, will be best understood from the following description, the appended claims and the accompanying drawings, in which:

[0083] FIGS. 1a-1b show a pictorial of a multi-layered composition according to an alternative, adhered onto the surface of a substrate, such as a window pane, pharmaceutical vial, etc.

[0084] FIG. 1c shows a pictorial of a multi-layered composition according to alternative without TiO.sub.2 in between polysaccharide layers.

[0085] FIG. 2a-2b show a pictorial of a multi-layered composition according to an alternative, adhered onto the surface of a glass or ceramic substrate that is a container, such as a pharmaceutical vial, food-grade bottle, etc.

[0086] FIG. 3 shows an example of a polysaccharide, pullulan, that may be substituted with sterol groups and used to externally coat a glass or ceramic substrate as described herein.

[0087] FIG. 4 shows an example of a sterol unit, cholesterol, which may be attached onto a polysaccharide, such as cellulose or pullulan, for use in externally coating glass or ceramic substrates as described herein.

[0088] FIG. 5 shows a schematic of a polysaccharide unit adhered onto the surface of a glass or ceramic substrate, with metal oxides facilitating the connection as modifying agents, according to an alternative of the disclosure; used in this example is the priming metal oxide agent TiO.sub.2, the first polysaccharide cellulose, and the second polysaccharide pullulan bearing sterol cholesterol groups.

[0089] FIG. 6 provides profilometry data on the polysaccharide coating according to one alternative.

[0090] FIG. 7 provides surface morphology of a coated and uncoated area of a glass surface substrate according to one alternative.

[0091] FIG. 8 provides infrared spectra data for a polyurethane suitable for an outermost coating according to one alternative.

[0092] FIG. 9 provides calorimetry data demonstrating superior thermal resistance of a coated glass bottle coated compared to an uncoated glass bottle.

[0093] FIG. 10 provides a Fourier-transform infrared spectroscopy of a polysaccharide inner layer according to one alternative.

[0094] FIG. 11 provides an Ultraviolet-visible spectroscopy of an outer functional (polyurethane) layer according to one alternative.

DETAILED DESCRIPTION OF THE DISCLOSURE

[0095] The present disclosure will now be described more fully, with reference to the accompanying drawings, in which several alternatives are shown. This disclosure may be embodied in many different forms and should not be construed as limited to the alternatives set forth here.

[0096] Within the context of this application, the term derivative when used with respect to a monomer, oligomer, or polymer of a hydrocarbon, anhydride, acrylic or urethane means that the monomer, oligomer, or polymer of the hydrocarbon, anhydride, acrylic or urethane has at least one modification to the side chain groups and/or functional units. The at least one modification to the side chain group and/or functional units may be the alteration, addition, or reduction of single atoms, halogens, straight-chain or branched alkyl, alkenyl, alkynyl, aryl, alkoxy, aryloxy, aromatic, hydroxy, carboxy, nitro, cyano, isocyano, thiocyano, isothiocyano, or azide groups to one or more repeating units of the monomer, oligomer or polymer.

[0097] As used herein, the term thermal insulation means preventing thermal induction, reducing thermal induction, or delaying the transfer of thermal energy from the external environment into the internalities of the substrate.

[0098] As used herein, the term thermal resistance means the ability of a substrate to delay an increase in its internal temperature in the presence of external heat. According to one alternative of the disclosure, coating a substrate with a multi-layered composition as described herein increases the thermal resistance of the substrate.

[0099] As used herein, the term pharmaceutical agent means any active pharmaceutical ingredient known the art in view of the present disclosure. Preferably, a pharmaceutical agent is a biopharmaceutical agent. Biopharmaceutical agents are typically sensitive to heat and temperature fluctuations, e.g., temperature increases. Examples of biopharmaceutical agent include, but are not limited to, vaccines, monoclonal and recombinant-antibody drugs, genetic and cellular therapies, and other biologic drugs.

[0100] As used herein, the term biocompatible refers to a substance or material that is not harmful or toxic to living tissues, animals, etc.

[0101] Referring now to FIG. 1a) there is shown a multi-layered composition 10 applied on an external surface of a substrate 20 modified with a first layer 30 of modifying agent TiCl.sub.4 and a second layer 40 of modifying agent TiO.sub.2 resulting in a modification layer 50, followed by a single layer comprising a polysaccharide, with or without sterol group substitutions forming an inner layer 60, with an outer functional coating 70 and an optional second outer functional coating layer 80.

[0102] FIG. 1b shows a multi-layered composition 10 applied on an external surface of a substrate 20 modified with a first layer 30 of a modifying agent TiCl.sub.4 and a second layer 40 of modifying agent TiO.sub.2 forming a modification layer 50, followed by one layer 90 of polysaccharide, with or without sterol group substitutions, followed by a layer 100 of modifying agent TiO.sub.2 followed by a polysaccharide layer 110 with or without sterol-group substitution, forming an inner layer 120 and an outer functional coating layer 130. It is advantageous for the purposes of the disclosure to have the penultimate polysaccharide layer to be substituted with sterol-groups; in one alternative, the layer comprising the modifying agent as shown in FIG. 1a) is from about 0.01-3 m thickness, in another alternative from about 0.1-0.5 m thickness, and in another alternative, from about 2-3 m thickness, depending on the number of layers deposited onto said substrate surface. The layer comprising the polysaccharide as shown in FIG. 1a) is 3-200 m in thickness; and the outer functional layer as shown in FIG. 1a) has an overall thickness of 1-10 m.

[0103] FIG. 1c is similar to FIG. 1b save for the lack of a TiO.sub.2 layer between the polysccharide layers.

[0104] The disclosure relates to a multi-layered composition for coating an external surface of a substrate to provide thermal insulation to said substrate, and increase said substrate's thermal resistance against temperature fluctuations in the immediate external environment of said substrate. A substrate as used herein is any material bearing free hydroxyl (OH) groups. In one alternative, said substrate is selected from the group consisting of glass, ceramic and combinations thereof. Additionally, in another alternative, the substrate may be flat, curved, or shaped as an open or closed container. A container may be any size or shape, and is not limited to any particular size or shape. In the case where the substrate is an open or closed container, the thermal insulation and resistance are also imparted onto any contents contained within the substrate. For the examples specified in this disclosure, borosilicate glass was used as the substrate.

[0105] In one alternative, the coating disclosed herein may comprise several layers during application (deposition) onto a substrate, to ameliorate adherence of said coating to said substrate and thermally insulating properties to the substrate and any contents enclosed within the substrate. The layers are described here by the sequential order of deposition, and provided with examples for the purpose of better narration without limiting the scope of this disclosure. It should be noted that the order, repeatability, and thickness of each layer used during deposition onto the substrate may be modified by those skilled in the art for unique application cases such as externally coating pharmaceutical grade glass containers for medical products.

[0106] The first layer (also known as the modification layer), as a part of the disclosed composition, may be applied to the external surface of the glass or ceramic substrate directly, or may be applied on top of an existing functional or non-functional coating layer or layers on the substrate, provided that such existing functional or non-functional coating layer or layers possesses free hydroxyl groups. This first layer comprises one or more inorganic and/or organic compounds that bind to the free hydroxyl groups on the external surface of the substrate, or an existing functional or non-functional coating layer, to improve the uniformity of the functional groups on the substrate surface on a molecular level, and to initiate the functionalization of the external face of the substrate or the pre-existing functional or non-functional coating layer. Examples of such inorganic and organic compounds include, but are not limited to TiCl.sub.4. Further, the modification layer comprises at least one inorganic oxide selected from the group consisting of TiO.sub.2, SiO.sub.2, InSnO.sub.2, and ZnO. Example of an organic compound includes, but is not limited to, siloxane. This modification layer may be applied by dissolving the inorganic compound in a solvent (such as a polar solvent) including but not limited to water, acetyl acetone, acetonitrile, ethanol and methanol, forming a modification solution or paste, then applying the modification solution or paste onto the substrate by any method known in the art, in view of the present disclosure, such as sputtering, vapor deposition, spraying, wiping (with a cloth containing the modification solution), dipping, powder deposition, electrostatic deposition, rolling, heat treatment, cold treatment, or other suitable techniques.

[0107] Aqueous or gaseous by-products may form during the application of the inorganic oxide (due to displacement of ions), which may require evaporation or drying by atmospheric air. Improvements of hydroxyl uniformity on the substrate surface or pre-existing coated layer may be accomplished by applying several coats of the inorganic oxide layer once a first coat is cured. Curing typically takes about 15 minutes. In one alternative, the application of said layer(s) do(es) not occlude the transparency of the substrate beyond the point required for its designated use. For example, in food or pharmaceutical containment applications, the transparency and appearance of the container or vial can be important.

[0108] In another alternative, the subsequent layer comprises a monomeric, oligomeric, or polymeric polysaccharide optionally substituted with one or more sterol groups. In one alternative, the polysaccharide is sterol substituted in the range of 0-30%. In another alternative, the polysaccharide is sterol substituted in the range of 1-5%. While monomeric polysaccharides may also be used, in one alternative, more than 90% w/v of the polysaccharides used in the disclosed composition are oligomeric or polymeric, and are preferably polymeric. In one alternative, multimeric polysaccharides are preferred primarily for two reasons: the first being most polysaccharides are produced and supplied in the form of multimers, and the second being multimeric networks of polysaccharides are generally of lower density and have more pores that can entrap gases, which are poor heat conductors. Examples of saccharides that may be used include, but are not limited to, glucose, fructose, galactose, maltose, dextrose, pullulan, sucrose, lactose, cellulose, and trehalose. This subsequent layer may be applied by dissolving the saccharide in a solvent forming a solution or paste, then applying the solution or paste onto the substrate by any method known in the art in view of the present disclosure, such as sputtering, vapor deposition, spraying, dipping, powder deposition, electrostatic deposition, or other suitable techniques. Aqueous or gaseous by-products may form during the displacement reaction, which may require evaporation or drying by atmospheric air. This layer provides thermal insulation and thermal resistance to the surface of the substrate and any contents enclosed by the substrate. The extent of thermal insulation and thermal resistance offered by this coating layer may be enhanced by repeatedly applying several times. In one alternative, the application of said layer(s) do(es) not occlude the transparency of the substrate beyond the point required for its designated use.

[0109] Following application of the saccharide layer, there is an option to subsequently coat the substrate with an outermost functional layer, or to repeat the initial functionalization step where hydroxyl groups are modified to better accommodate further saccharide coatings. In the case where an outermost functional coating layer is desired, a monomer, oligomer, or polymer of a hydrocarbon, anhydride, acrylic, urethane or a derivative of any of these with optionally modified side chain units or functional units may be used for the purpose of providing at least one specialized function to the substrate and its externally coated layer(s). Such at least one specialized function may be, but is not limited to, polishing, optically clear, anti-weathering, anti-scratch, anti-frictive, anti-microbial, anti-oxidation, anti-frost, anti-wetting, anti-cracking and combinations thereof. Examples of compounds that may be used include, but are not limited to, polyurethane, polyvinyl, polyethylene, and mixtures or hybrids or derivatives thereof. Such specialized functional layers are known to those skilled in the art. The use of these functional layers is listed here because it is complementary to the saccharide-based coating layers disclosed.

[0110] In one alternative, in the case where a polysaccharide coating layer is the penultimate layer, a sterol-group substitution may be desired on the polysaccharide units. One or more sterol-group attachments may be added onto the polysaccharides, in one of the following formats: (1) the same type of sterol molecule attached one or multiple times onto the same polysaccharide unit, or (2) the same type of sterol molecule attached one or multiple times onto different polysaccharide units in a homogenous mixture, or (3) two or more different sterol molecules attached one or multiple times onto the same type of polysaccharide unit, or (4) two or more different sterol molecule attached one or multiple times onto different polysaccharide units in a homogenous mixture to form a single coating layer. In one alternative, using sterol-substituted polysaccharides in the penultimate layer comes from the hydrophobicity offered by the polysaccharide's sterol-substitutions. Toward the outer layers of an externally coated glass or ceramic substrate, hydrophobicity is desired to decrease interaction of the coating with water or moisture in the atmosphere, and therefore elongate the shelf-life of the contents within the substrate. Examples of sterol-substituted polysaccharides, by way of example and not as to limit the scope of this disclosure, include cholesterol-bearing pullulan and cholesterol-bearing cellulose and combinations thereof. Other examples of sterol groups that may be used include, but are not limited to, cholesterol, ergosterol, cortisol and combinations thereof.

[0111] In one alternative, the external coating process may or may not include all of the disclosed steps or be sequentially processed in the particular sequence discussed, and the presently disclosed manufacturing process and coating methods encompass any sequencing, overlap, or parallel processing of such steps. The various alternatives may be provided in any suitable combination with one another. While the coating layers are described in the present disclosure, for clarity of understanding, as adjacent layers overlying one another sequentially, one or more of the coatings may seep into or combine with one or more of the other coatings that it is in direct contact with, and the layers as described are not necessarily discrete layers once coated on a substrate.

[0112] Referring now to FIG. 2a), there is shown a plurality of layers as applied to an external surface (or face) of a glass container 140. In this alternative, the external surface is first coated with a layer 150 containing TiCl.sub.4, followed by a layer 160 containing TiO.sub.2 resulting in the formation of a modification layer 170. This is followed by a layer 180 containing polysaccharide followed by another layer 190 containing TiO.sub.2 followed by a layer 200 containing polysaccharide (with or without sterol-group substitution) forming an inner layer 210, and finally a polyurethane layer forming an outer functional layer (or coating) 220.

[0113] Referring now to FIG. 2b) there is show a composition similar to FIG. 2a) save for the lack of TiO.sub.2 layers in between the polysaccharide layers (inner layer) and the modification layer comprises siloxane 230.

[0114] Referring now to FIG. 3, there is shown pullulan as an example of a polysaccharide as per the disclosure.

[0115] Referring now to FIG. 4, there is shown cholesterol as an example of a sterol unit as per the disclosure.

[0116] Referring now to FIG. 5, there is shown the external face (surface) of a substrate with a polysaccharide unit adhered onto the surface of the substrate, with metal oxides facilitating the connection as modifying agents. In this Figure, there is seen the priming metal oxide agent TiO.sub.2, the first polysaccharide cellulose, and the second polysaccharide pullulan bearing sterol cholesterol groups.

[0117] Referring now to FIG. 6, there is shown profilometry data on a glass substrate with a modification layer followed by a polysaccharide coating. As best seen here, the surface morphology at the edge of a single coating with an average thickness (TIR) of 8.92 m. As best seen here, section L1-L1 identifies the start of uniform thickness of the coated glass substrate. Area R1-R1 identifies an area of untreated glass surface. As further shown in the FIG. 6, the slope of 1.51 provides a metric to determine concentration of solution coating applied and provides a measurement to choose concentration based on requirements of coating.

[0118] Referring now to FIG. 7, there is shown a microscopic image of borosilicate type 1, laboratory grade (ThermoFisher, US) glass surface with the darker area being coated with a multi-layer composition described herein and the lighter area (parts of the upper and lower right quadrants) not coated as it relates to the profilometry of FIG. 6.

[0119] Referring now to FIG. 8, there is shown an infrared spectra of a polyurethane (branched polyurethane substituted with a benzothiazole with a substitution degree of 3%) useful as an outermost coating (layer) to enhance the physical robustness and anti-moisture properties of the overall coating on the substrate.

[0120] Referring now to FIG. 9, there is shown calorimetry data of a coated (treated) glass bottle as per Example 2 versus an uncoated (untreated) glass bottle (8 mm clear glass screw top sampler vial, ThermoFisher, US). As may be seen by the data, the heat transfer is delayed with the coated glass bottle versus the uncoated glass bottle. Both vials of the same substrate and content were removed from a cool environment and placed in an environment where heat is slowly increased (endpoint at 35 C.) for 1 h12 m. Throughout the time period, a two-probe digital thermometer was used to measure the respective temperatures of the external environment of the glass bottles and the internal contents of the coated (Treated) or uncoated (Untreated) bottles at 10 s intervals. The moving averages taken from 3 consecutive temperature readings result in FIG. 9. As seen in FIG. 9, the surface coating allows for a delay in the thermal energy transfer between the external environment into the internal content of the coated bottle.

[0121] Referring now to FIG. 10, there is depicted a FTIR spectroscopy of a polysaccharide inner layer of a 10-30% alkyl-substituted carboxymethyl cellulose derivative without sterol substitution.

[0122] Referring now to FIG. 11, there is depicted a UV-Vis spectroscopy of an outer layer of a branched polyurethane with benzothiazole-substitutions with 3% degree of substitution. This is an example of an outer layer for coating pharmaceutical containers as it is transparent (no absorbance within the visible spectrum between 400-800 nm).

[0123] According to alternatives of the disclosure, coating an external surface of a substrate, such as an open or closed container, with a multi-layered composition of the disclosure may be used to provide thermal insulation to the substrate as well as to the contents of the container.

EXAMPLES

[0124] With the sole intention of illustrating certain principles and practices of the disclosure, and by no way limiting the scope of the disclosure, we provide here example compositions that may be used to externally coat a pharmaceutical glass vial for thermal insulation.

Example 1

Coating Pharmaceutical Grade Borosilicate Glass Vials

[0125] Six identical pharmaceutical grade borosilicate glass vials were coated by multiple layers. The exteriors of the vials were dipped in an 0.05 M aqueous solution of TiCl.sub.4 for 2 hours at 70 C., upon removal from the aqueous solution, excess solution on the vials were dried by atmospheric air at room temperature for 15 minutes Immediately following this, the vials were slowly lowered (0.1 cm/s) into an aqueous solution of titanium tetraisopropoxide (TTIP) (1:3 molar ratio), acetyl acetone (1:1 v/v), 1-propanol (1:1 v/v), 0.1 M nitric acid (6:1 v/v), Triton X-100 (1:100 v/v) and PEG 3000 (1:100 v/v) to form the TiO.sub.2 layer. The vials were exposed to the TTIP solution for 2 hours at 70 C. The vials coated with the TiO.sub.2 layer (modification layer) were annealed at 450 C. for 15 minutes. The TTIP dip coating and annealing process may be repeated several times to increase the thickness of the modification layer. In this example, the entire modification layer (TiO.sub.2 and TiCl.sub.4) possessed a total thickness in the range of 2.3-3 m as produced by dipping the vial 4 times (each vial was dipped subsequent to annealing of the previous deposition) . Upon cooling, the vials were then slowly dipped (2 cm/s) in an aqueous solution of polymeric pullulan (MW=50,000-90,000 g/mol with average approx. 75,000 g/mol; 0.00375% w/v). at 50 C. for 2 hours. Once air-dried, the vials were heated to 120 C. for 2 hours to evaporate any remaining solvent.

Example 2

Coating a Pharmaceutical Grade Borosilicate Glass Vial

[0126] A pharmaceutical grade borosilicate glass vial was coated separated into multiple layers, each layer comprising of a portion of the components. The vials were dipped in an 0.05M aqueous solution of TiCl.sub.4 for 2 hours at 70 C., with the excess solution dried by atmospheric air at room temperature. Immediately following this, the vials were slowly lowered (0.1 cm/s) into an aqueous solution of titanium tetraisopropoxide (TTIP) (1:3 molar ratio), acetyl acetone (1:1 v/v), 1-propanol (1:1 v/v) and 0.1 M nitric acid (6:1 v/v) to form the initial TiO.sub.2 layer. Triton X-100 (1:10 v/v) and PEG 3000 (1:100 v/v) were later added to further modify the structure of this TiO.sub.2 layer. The vials were coated for 2 hours at 65 C. The TiO.sub.2 layer were annealed at 450 C. for 15 minutes. This dip coating process can be repeated several times to increase the thickness of the coating. The vials were then slowly dipped (2 cm/s) in an aqueous solution of sodium carboxymethyl cellulose (MW=200, 000-300,000 g/mol with average approx. 250,000 g/mol, 1.2 degree of substitution) at 50 C. for 2 hours. Once air-dried, the vials were heated to 120 C. for 2 hours to evaporate remaining solvents.

[0127] In particular alternatives of the disclosure, a substrate, such as a glass substrate, is coated with layers according to one of the following: [0128] 1. Substrate-TiCl.sub.4-(TiO.sub.2).sub.nTiCl.sub.4-(Cellulose).sub.m-Outer functional layer [0129] 2. Substrate-TiCl.sub.4-(TiO.sub.2).sub.nTiCl.sub.4-(Pullulan).sub.x-Outer functional layer [0130] 3. Substrate-TiCl.sub.4-(TiO.sub.2).sub.nTiCl.sub.4-(Cellulose).sub.m(TiO.sub.2).sub.y-(Pullulan).sub.x-Outer functional layer

[0131] where n, m, x, and y represent a number of coatings of each of the layers, and each of n, m, x, and y is independently an integer equal to or greater than 1.

[0132] In the annealing process in which TiO.sub.2 is heated to 450 C. for 15 minutes, cracks within the TiO.sub.2 layer may form. A second treatment of TiCl.sub.4 may fix these cracks by filling in the space resulting from the cracks within the TiO.sub.2 layer. This allows for a more even surface coating.

Example 3

Coating a Single Surface of a Flat Borosilicate Glass

[0133] A flat piece of borosilicate glass was coated with multiple layers. The vials were dipped in 5% w/v siloxane solution in 1:2 acetone: water solution for 30 seconds as the modification layer, followed by a slow wiping motion with a microfiber cloth at ambient temperature to remove excess solution on the surface. The glass was then coated with a uniform layer of carboxymethyl cellulose bearing polyethylene glycol branches (MW=200,000-300,000 g/mol, 1%w/v aqueous solution) via electrospray ionization (in this example 35 ml of solution is used in 100 depositions). This cellulose solution cures by exposure to air for 2 hours, by evaporating the solvent. To ensure the uniformity and desired thickness of more than 40 m, the electrospray process is repeated 3 times, each time after the previous deposition has been fully cured. After this inner layer is fully cured, a polyurethane outer coating (30% w/v) is brushed on to the surface lightly to create a thin layer, and cured using moist air for 45 minutes at room temperature.

[0134] In particular alternatives, a substrate, such as a glass substrate, is coated with layers according to one of the following: [0135] 1. Substrate-Pre-modification layer-(polyethylene glycol-bearing Cellulose).sub.m-Outer functional layer where m represent a number of coatings applied for the modified cellulose layer, and is an integer between 1 to 5 (preferably 3).

Example 4

Coating a Pharmaceutical Grade Borosilicate Glass Vial

[0136] A borosilicate glass vial was coated with separated into multiple layers. In this example, the modifying layer is omitted. The glass vial was lowered into a solution of carboxymethyl cellulose bearing polyethylene glycol branches (MW=200,000-300,000 g/mol, 1%w/v aqueous solution) with a lowering vertical movement speed of 0.1 cm/s. After 2 minutes in the solution, the glass vial was raised from the solution at the same vertical speed. This cellulose coating was cured by exposure to air for 2 hours at room temperature, by evaporating the solvent. To ensure the uniformity and desired thickness of more than 40 m, the dipping process is repeated 2 times. After this inner layer is fully cured, the vial is then lowered (0.1 cm/s) into a polyurethane outer coating solution (10% w/v), upon complete submersion, the vial was removed from the solution and cured using moist air (5% water) in an incubator for 45 minutes at room temperature. To provide enhanced robustness to the coating composition, this outer coating application was repeated once more.

[0137] In particular alternatives, a substrate, such as a glass substrate, is coated with layers according to one of the following: [0138] 1. Substrate-(polyethylene glycol-bearing Cellulose).sub.m-Outer functional layer.sub.n where m represents a number of coatings applied for the modified cellulose inner layer, and is an integer between 1 to 5 (preferably 3); where n represents a number of coatings applied for the polyurethane outer layer, and is an integer between 1 to 2 (preferably 2).