US20030165569A1

US20030165569A1 - Composition for topical substance delivery

Info

Publication number: US20030165569A1
Application number: US10/372,740
Authority: US
Inventors: Guy Levy; Allan Staley; James Rancourt
Original assignee: Soluble Systems LLC
Current assignee: Soluble Systems LLC; Polymer Solutions Inc
Priority date: 2000-05-30
Filing date: 2003-02-24
Publication date: 2003-09-04
Also published as: US6592860B1; JP2004509844A; CA2410706C; AU2001261540B2; US20070237825A1; MXPA02011722A; BR0111390A; EP1299157A1; WO2001091682A8; WO2001091682A1; CA2410706A1; US20050214334A1; AU6154001A

Abstract

A polymerized hydrogel composition for hydrating or dehydrating a surface, particularly a dermatological surface, to which it is applied and a method for forming the composition. The composition is comprised of a mixture of two polymerizable materials, a two-part redox catalyst system and a two-part polymerization medium. The percentage by weight of each element in the composition may be varied within stated percentage ranges and depending to the desired application. The rate at which hydration or dehydration occurs may be controllably altered by varying the percentages of certain of the composition elements and by adding either or both of a fibrous filler material and a humectant to the composition.

Description

CROSS-REFERENCES TO RELATED APPLICATIONS

This application is a continuation-in-part of U.S. Application Ser. No. 09/580,679, filed on May 30, 2000, also filed as PCT/US01/15462 on May 11, 2001.[0001]

TECHNICAL FIELD

The subject invention relates generally to the delivery of moisture to and removal of moisture from a dermatological surface, and, more particularly, to a composition for providing soluble medicaments and moisture to such surfaces.

BACKGROUND OF THE INVENTION

The ability to provide a controlled, variable release of soluble medicaments or aqueous substances in a topical manner is desirable for treating a variety of diseases and ailments. For example, the general aging of the population is accompanied by a concomitant increase in the number of cases of dry mouth, also referred to as xerostomia. This is a condition in which salivary flow is either decreased or undergoes a compositional change. Not only is this affliction irritating, it can also aggravate problems involving swallowing and speaking and may even lead to increased tooth decay. In the elderly xerostomia is particular dangerous since it may interfere with eating and result in malnutrition.

Furthermore, although it is known to have syringe applicators or encapsulated sponges for delivering medicaments or moisture, compositions used for the purpose of topical delivery of medicament generally do not typically exhibit any hydrodynamic properties which would enhance their delivery capability. Moreover, such compositions cannot provide the dual function of both delivering fluids to and removing them from a chosen site as desired.

Numerous issues must be addressed in developing such a product. First, the delivery system must be biocompatible since it can be used inside body cavities such as the mouth or elsewhere in direct contact with the skin. Second, the system must be pleasant and easy to use as it will be distributed to the general public. It should not be accompanied by any chemical or repellent taste or smell. Third, in cases where it is used inside the mouth, it must be smooth and comfortable. This point is particularly important since, due to dryness, the mouth may be prone to infection and is likely to be highly sensitive. A fourth consideration is safety. The product must exhibit resistance to microbial growth. Finally, such a product would have to exhibit physical stability, strength, resistance to cracking, tearing and crumbling and durability along with the capability to release or absorb a known amount of fluid at a predictable rate for a predictable period of time.

What is missing from the prior art is a dual-purpose delivery system for medicaments and moisture including a composition which is viscoelastic and functions as a hydrodynamic pump, easily releasing fluid in a variably controlled manner, and which may be used not only to deliver fluids to a desired site but, if desired, to remove them as well. In addition, such a delivery system must successfully address the issues described above.

SUMMARY OF THE INVENTION

The present invention relates to a hydrogel composition for hydrating and dehydrating dermatological surfaces.

The hydrogel composition is comprised of two polymerizable materials, a polymerization catalyst and a two-part polymerization medium. The polymerizable materials are a hydrophilic acrylate-based monomer and a crosslinking agent. In the preferred embodiment, the polymerizable materials are 2-hydroxyethyl methacrylate and ethylene glycol dimethacrylate, respectively. The polymerization catalyst is a redox initiator system. In the preferred embodiment, a two-part redox catalyst system is used comprised of ammonium persulfate and tetramethylethylenediamine. The polymerization medium is comprised of distilled water and a low molecular weight aliphatic alcohol such as isopropyl alcohol. A hydrodynamic hydrogel composition is formed from a combination of these materials which, after hydration, can release consistent amounts of moisture over a relatively long period of time onto a surface with which it is placed in contact. Alternatively, after dehydration, the composition can absorb moisture from a surface with which it is placed in contact.

A method for forming the hydrogel composition is also provided in which specified percentages by weight of all of the elements are mixed to achieve the desired composition. First, the two polymerizable materials are mixed with the polymerization medium. Then, the ammonium persulfate is added to the preexisting mixture. Only after the ammonium persulfate is thoroughly dissolved may the tetramethylethylenediamine be introduced to the mixture. The resultant composition must be transferred within two to three minutes to a desired mold. The molded composition sets up within between twenty and twenty-five minutes after which it may be removed from the mold and washed to remove the residual monomer from the molded composition.

A primary objective of this invention is to provide a hydrogel composition capable of hydrating or dehydrating a surface with which it is placed in contact.

An additional objective of this invention is to provide a hydrogel composition comprised of two polymerizable materials, a polymerization catalyst and a polymerization medium.

It is a further objective of this invention to provide a hydrogel composition based on use of a hydrophilic acrylate-based monomer, a crosslinking agent, a redox catalyst system, a low molecular weight aliphatic alcohol and distilled water.

Yet another objective of this invention is to provide a composition for use as a wound dressing which can either function to absorb fluids from a wound when used in a desiccated state or to hydrate wounds when applied thereto.

Still a further objective of this invention is to provide a composition for use in implanted hormone or other types of therapy wherein the composition could release medical materials over a prolonged period of time at a controlled rate.

Another objective of this invention is to provide a composition useful in field chemical sampling where it could absorb chemicals in the field and later release in a laboratory.

An additional objective of this invention is to provide a composition for managing dry eyes by hydrating areas around or in contact with the eye.

It is still another objective of this invention to provide a method for making a polymerized hydrogel composition capable of hydrating or dehydrating a surface with which it is placed in contact wherein distilled water, a low molecular weight aliphatic alcohol and two polymerizable materials are mixed together and the first part of a two part redox catalyst system is thoroughly dissolved in the resulting mixture before the second part of the two part redox catalyst system is added to the mixture.

A still further objective of this invention is to provide a composition in which both the moisture release rate and the moisture absorption rate are controllably variable.

Yet an additional objective of this invention is to provide a method for controllably varying the moisture release and the moisture absorption rates of a composition used in hydrating and dehydrating a surface by adding fibrous filler material to the composition.

It is yet a further objective of this invention to provide a composition which resists cracking, tearing and crumbling.

Another objective of this invention is to provide a method for controlling the amount of cracking, tearing and crumbling which occur while using the composition.

Still another objective of this invention is to provide a method for controlling the rate and quantity of absorption and desorption of fluid from a hydrogel composition by infusing a humectant into the composition.

A further objective of this invention is to provide a method for increasing the efficiency of polymerization of a hydrogel composition.

BRIEF DESCRIPTION OF THE DRAWINGS

The foregoing and other objects, aspects and advantages of the invention will be better understood from the following detailed description of the invention with reference to the drawings, in which: [0024]
FIG. 1 is a graph showing percent weight loss over time of a sample of the composition into which different amounts of a humectant had been infused. [0025]
FIG. 2 is a graph showing the initial rate of mass loss and mass loss over time of a sample of the composition into which different amounts of a humectant had been infused.[0026]

DESCRIPTION OF THE PREFERRED EMBODIMENT OF THE INVENTION

The moisture delivery and removal system of this invention is comprised of a composition used to absorb, retain and release medicaments and/or fluids. Table 1 identifies each element in the composition, the approximate percentage of the whole by weight which that element represents in any given amount of composition prior to initiation of the chemical reaction resulting in formation of the composition. A more detailed description of each element and its affect on the composition follows Table 1. [0027]

TABLE 1

Element Preferred % by weight Range % by weight

HEMA 26.2 26-35

EGDMA 1.3 1-1.8

AP .4 0.3-0.5

TEMED .2 0.1-0.3

Distilled water 65.4 62-72

IPA 6.5 0-11

Total 100.0
The composition includes two polymerizable materials. The main polymer is 2-hydroxyethyl methacrylate, or HEMA. It is easily polymerized using thermally activated free radical initiators, i.e. 2, 2′-azobisisobutyronitrile (AIBN), or redox catalyst systems. The monomer is water-soluble and the resulting polymer is very hydrophilic but insoluble. If HEMA exceeds approximately 35% by weight of the composition, the water release capability of the composition will suffer. Thus, by increasing the amount of HEMA in the composition, its water release rate would be reduced, while the absorptive rate of the composition would be increased. No substitute monomers are presently known to result in the creation of the same sponge-like hydrogel composition as HEMA when used in the proportions described above. However, several hydrophilic acrylate-based secondary monomers might be substituted for HEMA by adjusting the proportion of other elements in the composition within the ranges presented in Table 1. Such monomers include 2-hydroxyethyl acrylate, 2-hydroxypropyl acrylate and 4-hydroxybutyl acrylate. The second polymerizable material is ethylene glycol dimethacrylate, or EGDMA, which functions as a crosslinking agent and influences both the rigidity and/or stiffness of the resulting polymer and its release properties. The use of EGDMA results in a crosslinked network that has elastic behavior. The network is insoluble in all organic and aqueous based solvents. The dehydration of the network is reversible. EGDMA should represent between approximately 1% and 1.8% of the composition by weight. If less than 1% is used, the composition lacks structural integrity, while if more than 1.8% is used, the composition tends to become chalky and falls apart. Although adjustments from the prefeffed formulation within the percentage ranges presented in Table 1 would be required to achieve the desired release rate, other crosslinking agents which could be substituted for EGDMA include diethylene glycol dimethacrylate, trimethylpropane triacrylate and trimethylpropane trimethacrylate. [0028]
The preferred polymerization initiator is a redox catalyst system which is comprised of ammonium persulfate, or AP, functioning together with tetramethylethylenediamine, or TEMED, to catalyze the polymerization of the HEMA-EGDMA mixture. The use of AP does not influence the properties of the resulting polymer but does directly affect the rate of polymerization. In the preferred embodiment, 0.4% by weight of the AP is dissolved in water along with the other components and once a miscible solution is formed, 0.2% by weight of TEMED is added. The AP reacts with the TEMED to form a free radical on the diamine. This free radical then attacks the unsaturated sites of HEMA and EGDMA. The reaction then propagates from these growth sites. It would also be possible to substitute a thermally activated reaction catalyst such as 2,2′-azobisisobutyronitrile for both AP and TEMED. This catalyst becomes thermally activated above 60° C. so that polymerization occurs after heating the mixture of monomer, crosslinking agent, water and isopropanol to this temperature. [0029]
The polymerization medium is a combination of water and isopropyl alcohol (IPA). A high concentration of water is required for the microporous gel to form. Using water concentrations of less than 62% will result in creation of a homogeneous, clear hydrogel that holds large amounts of water but will not release the water at a desirable rate. Also the use of water allows the composition to be polymerized in a fully hydrated state giving it elastic behavior and permitting residual monomer to be easily removed. The ratio of HEMA to water in the composition affects the appearance, hardness and release rate of the resulting polymer. By increasing the amount of water in the composition, its release rate would be increased, while its absorptive rate would be decreased. However, when the water concentration increases above 72% structural integrity suffers. [0030]
The IPA serves three functions. First, by varying the alcohol concentration, both the moisture/medicament release rate and the absorption rate of the hydrogel resulting from the polymerization can be controlled. Increased IPA results in a decreased rate of water release in a mechanically deformed sample of the composition, while also decreasing the rate of water absorption in both a static and mechanically deformed sample of the composition. As a result, a composition having customizable release and absorption rates becomes available. However, when the concentration of IPA exceeds approximately 11% of the composition, the water release rate is reduced so much as to become impractical. By contrast, decreased IPA results in an increased rate of water release in a mechanically deformed sample and in an increased rate of water absorption in either a static or mechanically deformed sample. Moreover, decreased IPA also results in an increase in the maximum amount of moisture which the composition is capable of absorbing. Second, IPA aids in the polymerization of the composition. Gas chromatography results have demonstrated that a composition polymerized with IPA present has substantially less residual monomer remaining at the completion of the reaction than one polymerized without IPA. On average, a typical sample of the hydrogel polymerized with IPA contains residual HEMA of 0.02%, whereas such a sample polymerized without IPA contains residual HEMA of 0.10%. These results indicate use of IPA reduces residual monomer in the polymerized hydrogel by up to 80%. Third, the ability to wash the residual monomer out of the composition is enhanced by the presence of alcohol. This is important since the presence of monomer typically results in a distinctive taste or smell which may appear unpleasant to an eventual user of the composition who would be required to insert it into the oral cavity. If the polymerization medium were 100% water (i.e., representing 72% of the composition by weight and having no IPA), the composition would release an excessive amount of water and would be more malleable than desirable. Various low molecular weight aliphatic alcohols, such as methanol and ethanol, may be substituted for IPA as a secondary diluent without detrimental effect on the resulting composition. However, use of an aromatic alcohol such as benzyl alcohol would result in a polymer lacking structural integrity. [0031]
In order to make the composition, the following steps may be followed: [0032]
1) Distilled water and IPA (reagent grade) are weighed out in the proportions dictated in Table 1 above. [0033]
2) HEMA and EGDMA are weighed out in the same manner. [0034]
3) Appropriate amounts of AP are added and allowed to dissolve. The AP must be dissolved before proceeding. [0035]
4) After thorough mixing and total dissolution of the AP, the TEMED is added. The TEMED must be added last. At this point, the worker has approximately 2 minutes to get the water solution in the casting mold or other manufacturing device. After 20 to 25 minutes the polymerization reaction is complete. [0036]
5) The composition is removed from the cast media. When shaped test tubes are used as cast media, the device is removed by placing a needle along the edge of the glass at the interface between the test tube and the device. Water is syringed into the bottom of the test tube creating back pressure which forces the appliance out of the mold. Other removal techniques are possible depending on the cast media used. [0037]
6) The composition is then soaked in a large volume of water to remove any residual monomer. This washing period lasts for at least 24 hours. Alternatively, the composition may be boiled for no more than 30 minutes and then dehydrated in an oven at approximately 170 degrees F. [0038]
7) The washed composition may then be soaked in an aqueous environment which may be enriched with medicament(s) and/or flavor-enhancers, as desired. [0039]
The resultant composition is typically white, opaque and deformable with little force. In addition, it demonstrates a variety of significant features. It remains moist for at least eight hours. Furthermore, it is not chemically altered and does not decompose with dehydration and rehydration. There is no taste or smell associated with the composition as formulated above. It does not support significant growth of microscopic organisms on its surface under conditions analogous to those found in the human mouth. Finally it is both comfortable when applied to human tissue, such as oral tissue, and comfortably conforms to the contours of the anatomical location to which it is applied. Since it is not slippery, it remains in place relatively well once applied to a location. The composition of this invention is a hydrogel but differs from other hydrogels since it is able to both absorb and release fluids. Due to the particular polymerization media used, the composition demonstrates a microporous structure which can be used both to store and disperse fluids and/or medications onto surfaces placed in contact with it and, when not intentionally prehydrated, to absorb fluids from such surfaces. In a dry state, the composition tends to absorb fluids since it is quite hydrophilic, having a high affinity for water. In its hydrated state, due to its inherent hydrodynamic properties, mechanical deformation enables it to drive fluid into or onto an area with which it is in contact. [0040]
The moisture absorption and desorption characteristics and strength of the composition may be controlled and enhanced in several ways. Fibrous material may be added to the composition during the polymerization process so that these fibers are polymerized with the matrix. This may be accomplished either by mixing the fibrous material into the composition after the other elements have been mixed together or by pouring the composition over the fibrous material. The fibrous filler material may be chopped staple fiber, nonwoven fabrics, woven fabrics, spun-bonded fabrics, gauze, continuous filaments, or yarn. Fibrous filler material of virtually any chemical composition can be considered for inclusion in the hydrogel composition with a few key considerations. Because the hydrogel composition is rich in acrylate monomers and the polymerization is conducted in an alcohol/water mixture, the fibrous filler material must not be soluble in these liquids (water, acrylate monomers, alcohol). Because propylene glycol (PG), as explained below, can be used as a hydrogel modifier (humectant/plasticizer), the fibrous filler material should not be soluble in propylene glycol or other humectants or plasticizers. [0041]
Many fibrous filler materials are commercially available and can be used in the hydrogel composition. Commercially available fibers include natural fibers (cellulose, and silk, for example) and synthetic fibers (polypropylene, polyethylene, polyester, polytetrafluoroethylene, polyamide, and cellulose acetate, for example). Commercial availability, however, is not a requirement for fiber selection. Fibers known to possess high stiffness can also be used as fibrous filler material if warranted by the specific application or by a conscious decision based on environmental concerns. The fibrous filler material also need not be a single composition or a single form. For example, the hydrogel composition can be polymerized in the presence of a blend of polyester and cotton fibrous filler material. [0042]
By adding fibrous filler material to the composition, the mechanical properties of the hydrogel composition may be improved. When fibrous filler material is incorporated in the hydrogel composition, the flexibility and abrasion resistance of the composition do not deteriorate. Moreover, the inclusion of fibrous filler material markedly enhances the tear resistance of the hydrogel composition. Table 2 below compares the tear strength of the hydrogel composition as expressed in grams of force applied before tearing occurred when polyester gauze was added to two different thicknesses of the composition. In the first case, a single layer (or ply) of 0.5 mm thick gauze was impregnated with the composition and in the second case two layers (or plies), each of 0.5 mm thickness, were jointly impregnated with the composition. The test results indicate that, on average, the amount of force which must be exerted to tear the composition when a single layer of gauze was added increased by between approximately 26 and 37 times. [0043]

TABLE 2

0.5 mm thick hydrogel 1.0 mm thick hydrogel

0.5 mm 0.5 mm 1.0 mm 1.0 mm

with gauze without gauze with gauze without gauze

Trial

1 350 13.79 530 20.77

Trial 2 385 10.55 510 15.72

Trial 3 420 8.78 500 22.14

Trial 4 410 8.71 560 22.41

Average 391 10.46 525 20.26
Furthermore, the hydrogel composition is mechanically robust, having excellent resistance to cracking and crumbling. For example, even folding the hydrogel onto itself does not cause cracking. Rubbing the surface with a pencil eraser does not abrade hydrogel material from the surface. Note that thinner samples without fibrous filler have less bulk and are more susceptible to breaking apart than thicker samples having more bulk. The geometric shape of the hydrogel composition does not influence the crumbling of the surface except in the case of complex shapes in which there is not consistent bulk of the composition to support sharply divergent or projecting surfaces. e.g. an egg shape would be more resistant to crumbling than a honeycomb shape. Although the addition of a humectant such as PG (discussed below) does improve the plastic properties of the hydrogel to a certain degree, the hydrogel composition will crumble much more easily without the fiber filler than with the fiber filler, regardless of the PG concentration. [0044]
Selecting fibers that are composed of polar polymers as opposed to selecting non-polar polymers also alters the performance of the hydrogel composition. Polar polymers include cellulose, polyamides, and polyesters, among others. Polar polymers typically contain oxygen or nitrogen in the backbone of the polymer or as a constituent of the side groups on the main polymer chain. Non-polar polymers include polypropylene, polyethylene, and polytetrafluoroethylene, for example. [0045]

An additional purpose in selecting fibrous filler material that is composed of either polar or non-polar polymers is to control the absorption and desorption properties of the hydrogel composition. Polar polymers are hydrophilic and, therefore, will absorb water and other polar fluids so as to influence the rate and quantity of absorption and desorption of fluids. Table 3 demonstrates the moisture content at equilibrium of several polar and non-polar materials. Such information is readily available for other polar and non-polar materials.

	TABLE 3


	Moisture Content at Equil.

	Non-polar materials
	Polypropylene	0.1%
	Polyethylene	0.01 to 0.05%
	Polytetrafluoroethylene	<0.01%
	Polar materials
	Polyethylene terephthalate	0.3%
	Polyamide	3.5%
	Cellulose acetate	7.8%
	Cellulose	ca. 7.0%
	Silk	ca. 7.0%

The quantity of moisture absorbable by each material can be calculated from the information presented in the table and applied to the quantity of fibrous material added to the composition. If a polar polymer filler is used, both the rate of water loss and the amount of water loss over time will be reduced Consequently, by adding a predetermined quantity of a selected polar polymer filler to the composition during the polymerization process, the moisture absorption rate of the composition will be increased and the moisture desorption rate of the composition will be decreased. Similarly, by adding a polar polymer filler to the composition, the quantity of moisture that is released over time will be reduced. By contrast, if a non-polar polymer filler were added to the composition, there would be no effect on the rate or quantity of moisture absorption or moisture desorption of the composition. In addition, if a polar polymer filler is used, a stronger bond to the polar hydrogel composition will typically result than is the case for non-polar polymers fillers. However, if too much fiber is added to the composition, the resulting hydrogel will be highly dispersed and poorly organized, while the addition of too little fiber will result in a product that is more easily torn or pulled apart. [0047]
The ratio of hydrogel composition to fibrous filler content varies according to the type of fiber used and to the amount of pressure applied, if any is applied, to the composition-saturated fiber during polymerization. The ideal amount of fibrous filler is that amount necessary for all fibers to be completely and uniformly saturated with the other components of the composition. Stated differently, composition to which fibrous filler has been properly added has a predictable distribution of fibers throughout the composition. In one method of making the composition, gauze (or other fibrous filler material) may be placed on a glass pane, saturated with hydrogel composition, covered by a second glass pane and then subjected to pressure over the entire surface of the saturated gauze. A small amount of pressure creates a greater hydrogel/fiber ratio. Conversely, heavy pressure creates a smaller hydrogel/fiber ratio. For instance, if the gauze (fiber filler) is incompletely saturated with hydrogel composition, heavy pressure on the glass slab may allow the hydrogel composition to be completely “compressed” into the gauze. A sample created under greater pressure will have less hydrogel content and will therefore have less absorptive and desorptive capacity. Given the same amount of compression pressure, a 2 ply gauze will require twice the amount of composition of a 1 ply, a 3 ply requires three times the composition of a 1 ply, etc. Of course, other methods and means of applying compression pressure to the saturated fiber material may be used to accomplish the same result. Note that pressure is not always required to form the composition with fibrous filler material. It is only necessary to create an even distribution of fibers in the polymer mix so that the polymer is not pooled unevenly within the fibers. With more advanced molding methods, a precise mass of fibers could be mixed with a precise volume of polymer without pressure to accomplish the same uniform distribution. For example, the polymer and fibers could be blown together to achieve a uniform distribution of fibers within the composition without pressure. When pressure is applied, it is applied to the prepolymerized mix after the fibers are saturated and is applied only until the polymerization reaction is complete. Thus, the proper amount of fibrous filler material for use in the composition depends on the moisture absorption capacity of the type of fiber preselected for use in the composition and can be predetermined by calculating the amount of the particular fiber which must be added to the known amount of other elements of the composition to achieve full saturation of that fiber in the desired final volume of composition. [0048]
Fibrous filler material can also be used that has more specialized features. Specialized features include, but are not limited to, microporous fibers, hollow fibers, fibrillated or micro-fibrillated fibers, and fibers having a non-circular cross-section (tri-lobed or square). Such fibers absorb fluids using capillary action and wicking (physisorption) rather than relying solely on polymer-fluid interactions (chemisorption). Still other fibrous filler materials possess multiple specialized features: microporous hollow fibers, for example. Whereas polar, fibrillated fibers can absorb large amounts of fluid due to chemisorption, the same is not true for non-polar, fibrillated fibers. However, both polar and non-polar fibers can absorb significant fluid through physisorption. Thus, by the selection of the type of fibrous filler material added to the composition, both the mechanical properties and the hydrating behavior of the composition can be controllably manipulated. For example, where a stronger hydrogel composition is desired but it is not desired to influence the rate of loss of moisture or other fluids, inclusion of a non-polar filler material would be desirable. On the other hand, where reinforcement of the hydrogel composition is desired along with the ability to adjustably control moisture absorption and release rates, a polar filler material is preferable. Moreover, if the application for which a hydrogel is designed requires control over moisture absorption, a polar filler material is preferable, while if the application requires moisture desorption, a non-polar material is preferable. [0049]
A further method of altering and controlling the rate of absorption and desorption of fluid from the composition is by the infusion of a humectant into the hydrogel composition after polymerization of the hydrogel. The humectant is preferably added after the polymerization mixture is polymerized and has been washed. The amount of humectant which may be added depends on the specific application and desired result and may be added in an aqueous solution in an amount constituting between 0% and 100% of the aqueous solution. It may be added at the same time that flavors, medicaments and other active ingredients are added. Alternatively, the humectant may be added as an element of the pre-polymerization matrix. In such cases, the humectant is added any time before the final activator (TEMED) of the redox catalyst is added to the composition elements. The volume by weight of humectant added must fall in the range of 0% to 15% of the desired total volume by weight of the final composition. If more than 15% of total volume by weight is added, the polymer structure is compromised so that structural integrity is diminished. Humectants include propylene glycol, polyethylene glycol, glycerine, sorbitol, and edible polyhydric alcohols, for example. The humectant can be a single chemical compound or a mixture of two or more humectants. The actual performance of the hydrogel composition can be altered based on the chemistry and the concentration of the specific humectant or humectant blend that is incorporated into the hydrogel composition. For example, by increasing the amount of propylene glycol humectant that is incorporated into a hydrogel composition the total amount of water that is released (dose) is reduced to a predictable level, and the rate of water loss (flux, percent per minute, for example) is reduced. [0050]
FIG. 1 presents in graphic form the result of experiments in which propylene glycol (PG) was infused into the post-polymerized composition in different percentage levels and the resulting composition was left exposed to the air while weight measurements were taken over time. In the table accompanying the figure, PG is expressed as a percentage in a water, preferably distilled water, solution. For example, 25% PG is a solution with 25% PG and 75% water. One ply indicates one layer of gauze 0.5 mm thick and two ply indicates two layers of gauze having a total thickness of 1.0 mm. The total percent weight loss from a hydrated hydrogel composition tracks well with the percent propylene glycol that was incorporated into the hydrogel. This observation indicates that the hydrogel is only releasing water and is releasing no propylene glycol. Such behavior would be expected based on the boiling point of the propylene glycol at ambient pressure (187° C). [0051]
FIG. 2 shows in graphic form the mass loss of a non-covered sample of the hydrogel over time in the same experiments as those conducted to produce the weight loss results of FIG. 1. The importance of this graph is that it shows for a specific size and shape of hydrogel, the total amount of fluid that is released (the dose) is controllable. For example, the data points after the lapse of a specific amount of time can be compared to ascertain what percentage level of PG should be used in polymerizing the composition. Furthermore, for a specific size and shape of hydrogel, the rate of moisture loss, which is represented by the dotted lines in the graph, is controllable. 100451 The humectants that can be incorporated into the hydrogel composition serve the additional function of plasticizing the hydrogel composition. As a result, the dehydrated hydrogel composition can remain flexible in the dehydrated state. Without the humectant/plasticizer element the hydrogel composition can become glassy in the dehydrated state. The hydrogel composition can be engineered to retain the desired and required level of flexibility over a very large temperature range and over a large range of water concentrations by utilizing the appropriate concentration of humectant/plasticizer. Thus, humectant/plasticizer compositions can be selected to engineer the mechanical properties and hydrating behavior of hydrogel compositions to meet specific application-oriented criteria. For example, when one wants the hydrogel to be depleted of moisture and any medical or chemical additives, there would be no reason to incorporate humectant. For a “packaging application” for which a stable flexible cushion is desired, 100% humectant with no water may be used. For dry mouth applications, where one would never want the hydrogel composition to become hard and glassy, an intermediate amount of humectant may be used, such as 5 to 30%. [0052]
Yet another method for controlling the rate of release of water from the hydrogel composition is by controlling the geometry of the composition itself and, thereby, its exposed surface area. For example, a sheet of the composition with a specified thickness can be designed having holes of a specific diameter. Diffusion can occur through the surface of the hydrogel and through the surface area created by the edge of each hole. The increase in desorption rate from a perforated sheet compared with a non-perforated sheet can be calculated and predicted. Other geometries that can be produced to control the rate of water release include solid cylinders, hollow cylinders, and hollow cylinders with a non-circular central channel. An example of a cylinder with a non-circular central channel is a cylinder with an internal channel that is “star shaped”. The surface area of the internal “star” can be designed to equal or exceed the surface area of the external surface of the cylinder. The external cross-section of the hydrogel composition can also be non-circular. Examples of non-circular external cross-sections include oval, square, and star-shaped cross-sections. The profile of the hydrogel compositions (internal and external cross-sections) can be designed to meet the required mechanical property criteria and the desired hydrating behavior for specific applications. [0053]
The production of hydrogel compositions having specific shapes and specific structural features is preferably accomplished using molds. The mold may be fabricated from virtually any material with preferred materials being those that are not attacked by water, or the acrylate monomers, alcohols, humectants or plasticizers typically used to prepare hydrogel compositions. Glass and silicone rubber molds are typical choices for manufacturing molds for producing hydrogel compositions with specific shapes and specific structural features. [0054]
The efficiency of the polymerization process during formation of the composition can be improved by isolating the exterior, exposed surface of the composition from the atmosphere at what would otherwise be an air/polymer interface. The polymerization mixture can be covered with a piece of glass or with an oxygen impermeable film (butyl rubber, chlorinated polymer films, or wax, for example) to exclude air. Alternatively, one can purge the surface of the polymerization mixture with nitrogen, argon, helium, or other appropriate gases. [0055]
There are a variety of uses to which the composition may be put including, but not limited to, intervention to prevent fluid loss, wound dressings for absorptive purposes when used in a fully or partially desiccated state at surgical sites, decubitis ulcers, burns and other areas of tissue degradation. Furthermore, the composition can be used for implanted hormone therapy by forming it around a permanent reservoir which may be periodically recharged with medical materials. Still another use for the composition would be for management of abrasions and dry eyes which are a problem very analogous to dry mouth. For example, the loose space beneath the eyes can be implanted with a small wetting device fabricated from the composition, with or without a reservoir, where it functions to relieve dry eye problems. Yet another use of the composition would be inside the human body where it could deliver predefined doses of chemicals or medicaments to be released at controlled rates. By adding a radio-opaque contrast medium such as a barium salt during the manufacturing process, the composition could be located with an x-ray imaging device when used in this manner. Still an additional use for the composition is inside the mouths of patients experiencing dry mouth, otherwise known as xerostomia. Finally, the composition is useful in the area of field chemical sampling since it could absorb liquids in the field and permit transport to the laboratory where liquids could be released for study. The absorptive properties of the composition can be increased by either decreasing the water concentration, decreasing the alcohol concentration or increasing the HEMA concentration. Alternatively, any combination of two or more of these changes in concentrations may be used to achieve the same result. [0056]
The hydrated composition may be packaged in a medically appropriate manner such that adequate sterility is maintained, the package is tamper-proof and desiccation or shrinkage of the composition is prevented. Thereafter, the composition package can be distributed or marketed in any of a number of ways including catalog sales, delivery to pharmacies for over-the-counter sale or to health practitioners for direct use. Shelf life of the composition is extended since the composition resists microbiological attack. [0057]
During the application period, which is variable depending on whether steps to extend or shorten the absorption and desorption capability of the composition are taken, the composition releases or absorbs fluid. If desired, additional medicament or fluid may be introduced into the composition. Once desiccation has occurred, the composition may again be submerged in an aqueous solution, rehydrated, remedicated and reused, although such reuse is limited for hygienic reasons to the same user and typically cannot extend beyond a period of 30 days without unacceptable degradation of the composition. [0058]
Another use for the composition is in wound management. It is known that moisture in a noninfected wound promotes healing. Furthermore, clinical studies have shown that dry wound beds actually increase the chance of infection. These principles make use of the composition in wound management ideal. Moreover, the composition, when used in a hydrated state has a nominal binding affinity, meaning that it does not easily adhere to a wound site during periods of application. When strengthened by the addition of fiber material, the composition may be used alone as a bandage without any supporting device. The composition may be packaged in an aqueous solution prior to use in various sizes and shapes. Corresponding to the moist-packaged compositions would be dry-packaged adhesive stripes to hold the composition over the wound. The consumer or health practitioner could position the composition over the wound and then use the adhesive strip or some other type of band to hold it in place. When fiber material and/or humectant has been added to the composition, it retains its strength and plasticity when exposed to the air as it dehydrates. Nevertheless, wound pads may include a resistant backing with a permeable membrane and a reservoir incorporated therein that will allow medications to be released through the composition while providing further protection from dehydration. Alternatively, a separate mold form may be provided to cradle the composition on one side but which, when in use, leaves the other side of the composition exposed. Such a form may be rectangularly shaped so that it comfortably molds to the contours of the skin at the wound site. The form may have one or more smaller cavities therein for introduction through one or more appropriately placed loading portals of fluids and or medicaments to encourage uncomplicated healing. This is ideal for septic wounds and burns. An adhesive strip or band would hold the form in place. For hygienic reasons, it is preferable to dispose of a form used in this manner after one use although reuse after rehydration is certainly possible. With or without the mold form, the composition could be packaged with a chemical hot pack or cold pack adhered to it, depending upon the application. This would be especially useful for post-operative and therapeutic applications since it enables temperature control of the wound site as well as possible control of the flow of medication to the wound site. [0059]
The foregoing invention has been described in terms of the preferred embodiment. However, it will be apparent to those skilled in the art that various modifications and variations can be made to the disclosed composition and device without departing from the scope or spirit of the invention. The specification and examples are exemplary only, while the true scope of the invention is defined by the following claims. [0060]

Claims

What is claimed is:

1. A reusable, nonbioadhesive, microporous hydrogel composition for hydrating or dehydrating a surface with which the composition is placed in contact at a variable, controllable and customizable moisture release or moisture absorption rate comprised of:

a hydrophilic acrylate-based monomer in the range of 26% to 35% by weight of the composition;

a crosslinking agent in the range of 1% to 1.8% by weight of the composition;

a polymerization initiator;

water in the range of 62% to 72% by weight of the composition;

an aliphatic alcohol in the range between 0% and 11% by weight of the composition;

at least one humectant; and

a predetermined amount of a preselected type of fibrous filler material having known moisture absorption characteristics.

2. The composition of claim 1 wherein said fibrous filler material is insoluble in water, acrylate monomers, aliphatic alcohol, propylene glycol or humectant.

3. The composition of claim 2 wherein said fibrous filler material is further comprised of polar polymers.

4. The composition of claim 2 wherein said fibrous filler material is further comprised of non-polar polymers.

5. The composition of claim 2 wherein the predetermined amount of said fibrous filler material is that amount of said material which, based on the known moisture absorption capacity of said material, will achieve moisture saturation when mixed with a known volume of other composition elements to which it will be added.

6. The composition of claim 1 wherein the amount and type of said humectant is dependent on the rate and amount of moisture desorption desired in the composition.

7. The composition of claim 6 wherein said humectant is infused into the composition prior to polymerization and constitutes in the range of 0% to 15% of the desired total volume by weight of the final composition.

8. The composition of claim 6 wherein said humectant is infused into the composition after polymerization has occurred and constitutes in the range of 0% to 100% of the final total volume of the infusing solution.

9. A method for making a specified amount of a reusable, nonbioadhesive, microporous hydrogel composition useful for hydrating or dehydrating a surface to which it is applied at a variable, controllable and customizable moisture release or moisture absorption rate and for forming the composition into a desired shape based on use of a two-part polymerization medium, two polymerizable materials, a two-part redox catalyst system for polymerization initiation, at least one humectant and fibrous filler material having known moisture absorption characteristics, comprising the steps of:

weighing out an amount of distilled water as the first part of the polymerization medium within the range of 62% and 72% by weight of the amount of composition desired to be made;

weighing out an amount of a low molecular weight aliphatic alcohol as the second part of the polymerization medium within the range of 0% and 11% by weight of the amount of composition desired to be made;

combining the resulting distilled water and the resulting low molecular weight aliphatic alcohol into a mixture;

weighing out an amount of a first, hydrophilic, acrylate-based polymerizable material within the range of 26% and 35% by weight of the amount of composition desired to be made;

weighing out an amount of a second polymerizable material within the range of 1% and 1.8% by weight of the amount of composition desired to be made;

adding the resulting first and second polymerizable materials to the mixture;

weighing out an amount of the first part of the redox catalyst system within the range of 0.3% and 0.5% by weight of the amount of composition desired to be made;

thoroughly dissolving the first part of the redox catalyst system in the mixture;

further adding at least one humectant in the range of 0% to 15% of the desired total volume by weight of the final composition to the mixture;

weighing out an amount of the second part of the redox catalyst system within the range of 0.1% and 0.3% by weight of the amount of composition desired to be made;

adding the resulting second part of the redox catalyst system to the mixture;

blending fibrous filler material into the mixture in an amount thereof which, based on the known moisture absorption characteristics of the filler, will achieve moisture saturation when mixed with the known volume of other composition elements to which it will be added;

transferring the resultant mixture to a mold within approximately two minutes after adding the second part of the redox catalyst system to the mixture;

removing the composition from the mold within between twenty and twenty-five minutes after adding the second part of the redox catalyst system to the mixture; and

washing the molded composition in a large volume of water for a period of at least twenty-four hours.

10. The method of claim 9 wherein the blending step is replaced by the steps of:

placing a predetermined amount of the fibrous filler material onto a surface;

pouring the mixture over the fibrous filler material;

11. The method of claim 9 wherein, when a molding method is used in which a predictable distribution of a precise mass of fibers throughout a precise volume of polymer is not inherent, the following step is added after the blending step:

applying pressure to the exterior, exposed side of the composition until polymerization is complete.

12. The method of claim 11 wherein pressure is applied through a solid, flat surface placed on top of the exterior, exposed surface of the composition.

13. The method of claim 9 wherein the further adding step is omitted and is replaced after the washing step with the step of:

infusing at least one humectant into the composition constituting in the range of 0% to 100% of the final total volume of the infusing solution.

14. The method of claim 9 further comprising, after the transferring step, the step of:

covering the exterior, exposed surface of the composition during polymerization.

15. The method of claim 9 further comprising, after the transferring step, the step of:

purging the exterior, exposed surface of the composition with a suitable gas during polymerization.

16. A method for controllably increasing the rate and amount of moisture absorption of a reusable, nonbioadhesive, microporous hydrogel composition having a hydrophilic acrylate-based monomer with a range of between 26% and 35% by weight of the composition, a crosslinking agent with a range of between 1% and 1.8% by weight of the composition, AP with a range of between 0.3% and 0.5% by weight of the composition, TEMED with a range of between 0. 1% and 0.3% by weight of the composition, distilled water with a range of between 62% and 72% by weight of the composition, a low molecular weight aliphatic alcohol with a range of between 0% and 11% by weight of the composition, at least one humectant and fibrous filler material comprising any one or more of the following steps:

adding a predetermined amount of a preselected type of at least one polar fibrous filler material to the composition prior to polymerization;

altering the geometry of the composition so as to increase the exposed surface area in a given sample; and

if pressure is applied to saturate the fibrous filler material during polymerization, reducing the amount of pressure to which the composition is subjected during polymerization.

17. The method of claim 16 wherein the polar fibrous filler material has higher physisorption and chemisorption characteristics than other fibrous filler material.

18. A method for controllably decreasing the rate and amount of moisture desorption of a reusable, nonbioadhesive, microporous hydrogel composition having a hydrophilic acrylate-based monomer with a range of between 26% and 35% by weight of the composition, a crosslinking agent with a range of between 1% and 1.8% by weight of the composition, AP with a range of between 0.3% and 0.5% by weight of the composition, TEMED with a range of between 0.1% and 0.3% by weight of the composition, distilled water with a range of between 62% and 72% by weight of the composition, a low molecular weight aliphatic alcohol with a range of between 0% and 11% by weight of the composition, at least one humectant and fibrous filler material, comprising any one or more of the following steps:

if pressure is applied to saturate the fibrous filler material during polymerization, increasing the amount of pressure to which the composition is subjected during polymerization;

altering the geometry of the composition so as to decrease the number of exposed surfaces in a given sample; and

infusing a larger amount of humectant into the composition.