阅读说明：本技术 用于皮肤粘合医疗产品的缓冲粘合剂组合物 (Buffered adhesive compositions for skin-adhesive medical products ) 是由 扬·沃尔格默斯 梅特·麦克 卡斯滕·里霍夫 彼得·斯科夫 克里斯托弗·尼尔森 佩尔·拉迪福 于 2018-11-15 设计创作，主要内容包括：本发明提供了一种缓冲粘合剂组合物,其包含高分子量非中和聚合酸和高分子量部分中和聚合酸以及包含该组合物的产品,例如伤口敷料和造口皮肤屏障。(The present invention provides a buffered adhesive composition comprising a high molecular weight non-neutralized polymeric acid and a high molecular weight partially neutralized polymeric acid and products comprising the composition, such as wound dressings and ostomy skin barriers.)

1. An ostomy skin barrier, comprising:

a first binder comprising a high molecular weight polymeric buffer composition having a high molecular weight polymeric acid in a non-neutralized form and a high molecular weight polymeric acid in a partially neutralized form; and

a second adhesive having a composition different from the composition of the first adhesive.

2. The ostomy skin barrier of claim 1, wherein the second adhesive does not comprise a high molecular weight polymeric buffer.

3. The ostomy skin barrier of claim 1, wherein the second adhesive has a lower absorption capacity than the first adhesive.

4. The ostomy skin barrier of claim 1, wherein the second adhesive comprises a hydrocolloid.

5. The ostomy skin barrier of claim 1, wherein the non-neutralized high molecular weight polymeric acid is a high molecular weight polyacrylic acid and the partially neutralized high molecular weight polymeric acid is a partially neutralized high molecular weight polyacrylic acid.

6. The ostomy skin barrier of claim 1, wherein the first adhesive comprises 40 wt.% polyisobutylene, 16 wt.% styrene-isoprene-styrene copolymer, 5 wt.% liquid PIB, 4 wt.% polyethylene fibers, 20 wt.% crosslinked polyacrylic acid, and 15 wt.% crosslinked partially neutralized polyacrylic acid.

7. The ostomy skin barrier of claim 1, wherein the second adhesive comprises 55.5 wt% polyisobutylene, 14.5 wt% styrene-isoprene-styrene copolymer, 5 wt% polyethylene fiber, 8.3 wt% pectin, and 16.7 wt% carboxymethylcellulose.

8. The ostomy skin barrier of claim 1, wherein the first adhesive comprises 40 wt.% polyisobutylene, 16 wt.% styrene-isoprene-styrene copolymer, 5 wt.% liquid PIB, 4 wt.% polyethylene fiber, 20 wt.% crosslinked polyacrylic acid, and 15 wt.% cross-linked partially neutralized polyacrylic acid, and the second adhesive comprises 55.5 wt.% polyisobutylene, 14.5 wt.% styrene-isoprene-styrene copolymer, 5 wt.% polyethylene fiber, 8.3 wt.% pectin, and 16.7 wt.% carboxymethyl cellulose.

9. The ostomy skin barrier of claim 1, further comprising:

a first barrier surface;

a second barrier surface; and

wherein the first intumescent surface comprises the first adhesive and the second barrier surface comprises the second adhesive.

10. The ostomy skin barrier of claim 9, wherein the first barrier surface is an inner layer formed from the first adhesive and the second barrier surface is a backing layer formed from the second adhesive, wherein the backing layer extends to and beyond the inner layer to form an edge portion of the barrier.

11. The ostomy skin barrier of claim 9, wherein the first barrier surface is configured to contact a peri-ostomy area immediately adjacent the wearer's stoma.

12. The ostomy skin barrier of claim 10, wherein the second adhesive has a lower absorption capacity than the first adhesive, thereby reducing the likelihood of the edge portion undesirably expanding when in contact with fluid.

13. The ostomy skin barrier of claim 9, wherein the first barrier surface includes a release layer.

14. A wound dressing, comprising:

a flexible outer layer;

a first binder comprising a high molecular weight polymeric buffer composition having a high molecular weight polymeric acid in a non-neutralized form and a high molecular weight polymeric acid in a partially neutralized form; and

a second adhesive having a different composition than the first adhesive; and

wherein the first and second adhesives are applied to one side of the flexible outer layer.

15. A wound dressing according to claim 14, wherein the second adhesive does not comprise a high molecular weight polymeric buffer.

16. The wound dressing of claim 14, wherein the second adhesive has a lower absorbent capacity than the first adhesive.

17. A wound dressing according to claim 14, wherein the second adhesive comprises a hydrocolloid.

18. A wound dressing according to claim 14, wherein the non-neutralised high molecular weight polymeric acid is high molecular weight polyacrylic acid and the partially neutralised high molecular weight polymeric acid is partially neutralised high molecular weight polyacrylic acid.

19. The wound dressing of claim 14, wherein the first adhesive comprises 40 wt.% polyisobutylene, 16 wt.% styrene-isoprene-styrene copolymer, 5 wt.% liquid PIB, 4 wt.% polyethylene fibers, 20 wt.% crosslinked polyacrylic acid, and 15 wt.% crosslinked partially neutralized polyacrylic acid.

20. A wound dressing according to claim 14, wherein the second adhesive comprises 55.5 wt% polyisobutylene, 14.5 wt% styrene-isoprene-styrene copolymer, 5 wt% polyethylene fibres, 8.3 wt% pectin and 16.7 wt% carboxymethylcellulose.

21. The wound dressing of claim 14, wherein the first adhesive comprises 40 wt.% polyisobutylene, 16 wt.% styrene-isoprene-styrene copolymer, 5 wt.% liquid PIB, 4 wt.% polyethylene fiber, 20 wt.% crosslinked polyacrylic acid, and 15 wt.% cross-linked partially neutralized polyacrylic acid, and the second adhesive comprises 55.5 wt.% polyisobutylene, 14.5 wt.% styrene-isoprene-styrene copolymer, 5 wt.% polyethylene fiber, 8.3 wt.% pectin, and 16.7 wt.% carboxymethyl cellulose.

22. A wound dressing according to claim 14, wherein the first adhesive is applied to a central portion of the dressing and the second adhesive is applied to a terminal edge portion of the dressing.

23. The wound dressing of claim 22, wherein the second adhesive has a lower absorbent capacity than the first adhesive, reducing the likelihood of the terminal edge portion undesirably expanding when contacted by fluid.

24. A method of manufacturing an ostomy skin barrier, comprising the steps of:

forming a first adhesive to the first barrier surface, the first adhesive comprising a high molecular weight polymeric buffer composition having a high molecular weight polymeric acid in a non-neutralized form and a high molecular weight polymeric acid in a partially neutralized form; and

forming a second adhesive having a composition different from the composition of the first adhesive to a second barrier surface.

25. The method of claim 24 wherein the first adhesive has a higher absorbency than the second adhesive.

26. The method of claim 24, wherein the second adhesive comprises a hydrocolloid.

Technical Field

The present invention relates to the field of adhesive compositions for medical dressings and skin-adhesive devices, such as ostomy products, wound dressings and other medical products intended to be adhesively secured to the skin surface of a user. The invention relates specifically to adhesive compositions containing high molecular weight buffers and capable of absorbing liquids and maintaining normal skin pH levels, and to methods of making such compositions.

Background

In many medical applications, the product is adhered directly to the skin, for example in the case of a wound dressing or ostomy skin barrier. Such products must be securely applied to the skin so that they remain in place and must absorb any liquids that are generated beneath or adjacent to them, such as perspiration, wound exudate, liquid feces, and the like.

Wound dressings typically serve multiple functions to promote healing. These functions include absorption of wound exudate, pH adjustment to create an optimal healing environment and reduce microbial activity, and protection of wounds from infection. Many such wound dressings are self-adhesive and comprise an adhesive layer which is typically adhered to the skin of the wearer around the wound. It is well known that skin under a wound dressing is often inflamed.

Known wound dressings achieve this by using several separate components. For example, known dressings typically use hydrocolloids, such as carboxymethylcellulose (CMC), pectin, or gelatin, to absorb wound exudate. While some hydrocolloids are also capable of independently adjusting pH, the degree of pH buffering they can provide is limited by the amount of hydrocolloid available in the dressing, which in turn depends on the desired fluid handling characteristics of the dressing. The buffering effect of the hydrocolloid alone is not ideal.

In addition, it is often difficult to achieve both adequate absorption and pH control levels. Wound dressings need to have a certain degree of absorbency to control pH, and a certain degree of absorbency is often desirable in wound dressings. However, excessive absorption of liquid can lead to undesirable swelling of the wound dressing, leading to swelling and possible loss of adhesion. In some cases, too much liquid absorption can result in dissolution of the adhesive component, which is also highly undesirable.

Hydrocolloid-containing adhesive compositions are well known, for example, as those disclosed in U.S. Pat. nos. 5571080, 3339546, 4192785, 4296745, 4367732, 4813942, 4231369, 4551490, 4296745, 4793337, 4738257, 4867748, 5059169 and 7767291, the disclosures of which are incorporated herein by reference.

Hydrocolloids are commonly used in what are commonly referred to as hydrocolloid skin barriers or hydrocolloid wound dressings. Such skin barriers and wound dressings typically comprise a water-insoluble pressure sensitive adhesive as a continuous phase, wherein one or more hydrocolloid particles are dispersed in the adhesive as a discontinuous phase that absorbs liquid and swells.

The water-insoluble adhesive phase of commercial skin barriers and wound dressings is usually composed of Polyisobutylene (PIB) or styrene-isoprene-styrene (SIS) block copolymers or mixtures of these materials. The surface adhesion promoter may be modified by the addition of an adhesion promoter component.

Patients with permanent or temporary ostomies (colostomy, ileostomy, etc.) require a bag to contain the discharged faeces or urine. The bag is usually attached to the skin around the stoma and is provided with an adhesive skin barrier, which attaches the bag to the skin and absorbs liquid flowing from or generated by the skin around the stoma. The skin barrier is typically replaced every three to five days, but may be retained for up to one week. During use of the barrier, the skin around the stoma may become inflamed due to prolonged contact with the fecal material. Over time, inflammation can become severe.

In some applications, the periphery of the ostomy skin barrier has a tape border for added safety. The adhesive used for the border is typically an acrylic adhesive. As used herein, the term "skin barrier" is intended to include any skin barrier with or without an adhesive tape border.

Both wound exudate and feces contain proteolytic and lipolytic enzymes. These enzymes degrade the stratum corneum when contained in a closed, moist environment and cause the observed inflammation. Furthermore, since both wound dressings and ostomy skin barriers are typically removed and reapplied periodically, the integrity of the skin beneath them is compromised and inflamed more readily than normal skin.

Normal skin has a so-called "acidic film" which maintains the pH of the skin surface between 4.0 and 5.5 (slightly acidic). This pH range may promote the growth of beneficial microorganisms, retard the growth of harmful microorganisms, and help maintain skin integrity. At this pH level, the activity of proteolytic and lipolytic enzymes in wound exudate or feces (and the damage caused thereby) is not very severe. However, the pH of wound exudate and peri-stomal fluid is typically between 6.0 and 8.0. Such a higher than normal skin pH results in a significant increase in enzyme activity, leading to inflammation.

For wound dressings, it is often difficult to achieve both adequate absorption and pH control levels for the stomal skin barrier. The skin barrier needs to have a certain degree of absorbency to control the pH, which is often desirable. However, excessive absorption of fluid can lead to undesirable swelling of the skin barrier, leading to swelling and possible loss of adhesion. In some cases, too much liquid absorption can result in dissolution of the adhesive component, which is also highly undesirable.

The current skin barrier contains hydrocolloids, which have only a limited pH buffering capacity if gums and carboxymethylcellulose (CMC). They are capable of adjusting the pH to a desired range between 4.0 and 5.5 when exposed to water or saline. However, it is important to note that physiological fluids, such as stoma output or wound exudate, are also buffered, typically at near neutral pH levels. When current skin barriers are exposed to these fluids, the inherent strong buffering capacity of physiological fluids overwhelms the weak buffering capacity of the skin barrier. As a result, the pH of the skin barrier surface rises, approaching the pH of the liquid used to challenge the skin barrier. Therefore, it would be desirable to provide a skin barrier with enhanced pH buffering capacity. There is also a need to provide a skin barrier with optimal absorption properties.

In view of the above, it would be desirable to have an adhesive composition with a suitable buffer to maintain the pH of the skin under a wound dressing or ostomy skin barrier or similar product in the range of about 4.0 to about 5.5 without irritation to the user's skin and such an adhesive composition would have an optimal fluid absorption range.

Disclosure of Invention

According to one aspect of the present invention, there is provided a high molecular weight polymer buffered adhesive composition that is capable of optimal fluid absorption and pH buffering.

According to another aspect of the present invention, there is provided a wound dressing comprising a high molecular weight polymeric buffer composition capable of optimal fluid absorption and pH buffering.

According to another aspect of the present invention, there is provided an ostomy skin barrier comprising a high molecular weight polymer buffer composition capable of optimal fluid absorption and pH buffering.

According to another aspect of the present invention, there is provided a method of manufacturing a skin-adherent medical device, such as a wound dressing or an ostomy skin barrier, using a high molecular weight polymer buffer composition.

One embodiment of the invention is a wound dressing comprising a flexible outer layer and a high molecular weight polymer buffered adhesive composition applied to one side thereof, the adhesive providing pH buffering and optimal liquid absorption with minimal irritation to the skin coated with the adhesive.

Another embodiment of the invention is an ostomy skin barrier comprising a high molecular weight polymer buffered adhesive composition applied to one side thereof, which provides pH buffering and optimal liquid absorption with minimal irritation to the adhesive coated skin.

Drawings

The invention will be better understood from reading the following description of non-limiting embodiments, with reference to the attached drawings, in which:

figure 1 shows the dependence of absorption on water retention concentration for a set of barriers according to an embodiment of the present invention.

Figure 2 illustrates fluid absorption versus carbomer concentration in accordance with an embodiment of the present invention.

Figure 3 shows the correlation between the pH of the barrier surface and the carbomer concentration according to an embodiment of the present invention.

Fig. 4 shows the relationship between the pH value and the water retention concentration of the barrier surface according to an embodiment of the present invention.

Figure 5 shows an ostomy barrier comprising a plurality of adhesive components according to an embodiment of the invention.

Figure 6 shows a partial cross-sectional view of the ostomy barrier of figure 5.

Figure 7 shows a stoma barrier according to another embodiment of the invention.

Figure 8 shows a partial cross-sectional view of the ostomy barrier of figure 7.

Detailed Description

One embodiment of the present invention is directed to an adhesive composition comprising a high molecular weight buffer that absorbs liquids such as sweat, wound exudate, urine and fecal matter, adjusts the pH, and reduces enzyme activity. As will be appreciated, embodiments of the adhesive composition are suitable for use in medical applications such as wound care, e.g., wound dressings, ostomy barriers, and the like, and may be suitable for use in human and veterinary applications.

In particular, one embodiment of the present invention contemplates the use of high molecular weight polymers that are rich in acid sites. Polymers with polyacid functionality can be used as buffers by using mixtures of their protonated and neutralized forms. Any high molecular weight polymer having pendant carboxyl groups capable of partial neutralization is suitable for use in the present invention. Suitable polymers include, for example, polyacrylic acid and poly (2-alkylacrylic acid), wherein the alkyl chain is 1 to 5 carbons in length and can be straight or branched. Polymethacrylic acid is a preferred poly (2-alkylacrylic acid). Other suitable polymers are copolymers of any acrylic and 2-alkyl acrylic monomer, copolymers of the above monomers with maleic acid, olefin polymers substituted with side chains containing free carboxylic acid groups, e.g., polyvinyl alcohol esterified with di-, tri-or poly-acids (e.g., polyvinyl alcohol succinate), and the like.

As will be appreciated by those skilled in the art, the buffered adhesive compositions of the present invention may employ any high molecular weight polymer having partially neutralizable pendant carboxyl groups capable of maintaining the pH of the test product at less than about 6.0 in the phosphate buffered challenge test described in example 1.

A preferred embodiment of the present invention is a buffered adhesive composition comprising at least two high molecular weight polymers rich in acid sites, one of which is in non-neutralized form and the other of which is in partially neutralized form. The inventors have surprisingly found that the combination of non-neutralized and partially neutralized forms of high molecular weight polymers rich in acid sites allows for independent modification of the degree of absorption and pH control, a very desirable quality in adhesive compositions for medical devices attached to the skin of a patient, such as wound dressings or ostomy skin barriers.

The proportion of unneutralized partially neutralized polyacid and the degree of neutralization of partially neutralized polyacid are interrelated. The degree of neutralization of the partially neutralized polyacid may conveniently be from about 50% to about 100%, preferably about 75%. Whatever degree of neutralization is chosen, the proportion of unneutralized and partially neutralized polyacid should be adjusted to achieve the desired pH range of between 4.0 and 5.5 under the wound dressing or ostomy skin barrier. One of ordinary skill in the art of adhesive formulation can readily select the appropriate proportions of non-neutralized polyacid and partially neutralized polyacid to neutralize the partially neutralized polyacid to some extent.

In the preferred embodiment, the non-neutralized and partially neutralized forms of the high molecular weight polymeric acid can be present in a ratio of about 3:1 to about 1:4, and preferably from about 2:1 to about 1:1, for about 75% neutralized partially neutralized crosslinked polyacid. Together, the two forms of high molecular weight polymeric acid may comprise from about 10 wt.% to about 25 wt.% of the entire adhesive composition, and preferably from about 15% to about 20% of the entire adhesive composition.

Polymers particularly suitable for use in embodiments of the present invention include polyacrylic acid (PAA) and polymethacrylic acid (PMA). Both PAA and PMA are available from Sigma-Aldrich, where PAA and PMA are in various forms (e.g., powders and solutions) and have a range of molecular weights. Among acrylic acid derivatives, PAA is preferred because it has the highest density of carboxylic acid sites per gram of compound and therefore the highest degree of buffering per gram of compound. As used herein, "high molecular weight" PAA means greater than about 60000 daltons, up to several million daltons. The term has a similar meaning for PMA and other polymers described above.

One of ordinary skill in the art can readily determine the appropriate degree of neutralization for a particular polymer and application. Partial neutralization of PAA can be achieved by mixing PAA (plus water as appropriate) with a stoichiometrically appropriate amount of a strong base (e.g., NaOH) until the desired degree of neutralization is achieved. Other polymers may be treated similarly. Partially neutralized polyacids, such as PAA, are also commercially available.

PAA and its related polymers exist in cross-linked and non-cross-linked forms, and the degree of cross-linking can vary. The polymers used in the present invention are preferably crosslinked.

As previously mentioned, high molecular weight polymers, such as PAA and PMA, provide effective pH buffering and absorption of liquids, such as sweat, wound exudate or feces. More specifically, when the polymer is dispersed in the adhesive matrix, it functions similarly to hydrocolloids, such as pectin and CMC. That is, they absorb, swell and form a viscous solution, thereby causing adhesion to the wearer's skin. As will be appreciated, the high molecular weight polymers may be the only hydrocolloid component, or in other embodiments, they may be combined with other hydrocolloids, depending on the application of the wound dressing or skin barrier and the desired fluid handling capacity.

In one embodiment of the invention, the high molecular weight crosslinked PAA and the high molecular weight crosslinked portion neutralizes PAA binding with polyisobutylene and styrene-isoprene-styrene copolymer or polymer fibers (or both). In one such embodiment, the adhesive composition includes a crosslinked high molecular weight PAA, a crosslinked high molecular weight partially neutralized PAA, polyisobutylene, and a styrene-isoprene-styrene block copolymer. In another such embodiment, the adhesive composition includes a crosslinked high molecular weight PAA, a crosslinked high molecular weight partially neutralized PAA, polyisobutylene, a styrene-isoprene-styrene block copolymer, and a fiber, such as cotton or preferably a polyolefin, such as polyethylene or polypropylene.

The adhesive component of the composition of the present invention may be any material having pressure sensitive adhesive properties that has a strong affinity for the fibrous material (if fibers are used). It may be a single pressure-sensitive adhesive or a combination of two or more pressure-sensitive adhesives. Adhesives useful in the present invention include, for example, adhesives based on natural rubber, synthetic rubber, styrenic block copolymers, polyvinyl ethers, poly (meth) acrylates (including acrylates and methacrylates), polyolefins, and silicones. The particular adhesive considered to be a preferred material of the present invention is a polyolefin, namely Polyisobutylene (PIB), but other pressure sensitive adhesive materials having similar properties are believed to be suitable.

The fibers in the adhesive composition may be any fibrous material known in the art, but are preferably compatible with the tacky adhesive component, even fibrous materials having a strong affinity for the tacky adhesive component. Researches show that polyolefins such as polyethylene, polypropylene and the like have good compatibility with PIB and are easy to be wetted by the adhesive. Both are non-polar saturated hydrocarbons.

Preferably, the PIBs are present as relatively high molecular weight PIBs (molecular weight in the range of about 40000 to 60000). For example, the skin barrier for ostomy typically comprises 60000 molecular weight PIB, in the range of 50 wt.% to 65 wt.% or 40000 molecular weight PIB, in the range of 40 wt.% to about 55 wt.%. In addition, a combination of 40000 molecular weight and 60000 molecular weight PIB may also be used, for example 32.5 wt.% 40000 molecular weight PIB and 32.5 wt.% 60000 molecular weight PIB.

Whatever material is selected for the cushion adhesive composition of the present invention, it is highly desirable that the composition have at least a minimum absorbency. The buffering capacity of the composition of the invention is to some extent related to its absorption capacity. If absorption does not occur, the high molecular weight polymer buffer will not come into contact with wound exudate or fecal material and will therefore not be effective. Although compositions having a lower absorbency are included in the present invention, it is preferred that the compositions of the present invention have at least about 0.15g/cm as measured in the test of example 1²The absorption capacity of (1). Further, the absorption capacity of the cushion adhesive composition is preferably not more than 0.60g/cm². As shown below, the absorptive capacity of the buffered adhesive composition can be adjusted by varying the ratio of partially neutralized high molecular weight polymer to non-neutralized high molecular weight polymer, and one of ordinary skill in the art can readily adjust the absorptive capacity of the buffered adhesive composition to a desired level.

A preferred representative buffered adhesive composition of the invention comprises: 1) about 55.5 wt.% PIB, about 14.5 wt.% SIS, about 5% polyethylene fibers, about 15 wt.% crosslinked polyacrylic acid, about 10 wt.% partially neutralized crosslinked polyacrylic acid; 2) about 66 wt.% PIB, about 6.5 wt.% SIS, about 4% polyethylene fibers, about 14.5% crosslinked polyacrylic acid, about 9% partially neutralized crosslinked polyacrylic acid. Of the above components, PIB preferably has a viscosity average molecular weight of 40000 and the partially neutralized crosslinked polyacrylic acid is preferably 75% neutralized.

The following examples describe the manufacture and testing of exemplary embodiments of the present invention.