Patent Application
20220241322
The present invention relates generally to a gas composition and apparatus configured to treat wounds.
Being physical damage to surface tissues of the body, the wound is a general term for wounds with or without openings.
In most cases, a slight wound heals over naturally without recourse to any particular treatment. A severe wound usually heals over by way of natural healing power, too, if it is properly treated by suturing, skin grafting, etc.
In no little cases, however, wound healing takes too long time with respect to intractable ulcers such as bedsores, venous stasis ulcers, arterial ulcers, diabetic ulcers and radiation ulcers. In some cases, it takes too long time for patients undergoing an operation to heal operative wound primarily because of a lowering of their natural healing power caused by their own diseases or medication.
Of such intractable wounds, the bedsore observed in long bedridden patients is a necrotic skin ulcer caused by a long-standing application of certain or higher pressures to the skin.
In recent years, with aging of population, patients suffering from bedsores while spending long confined to bed have tended to increase in number. To deal with this situation, various proposals of therapeutic drugs or methods for treating wounds inclusive of bedsores.
For instance, Patent Publication 1 discloses that sodium glutamate is orally administrated to patients in the form of an internal medicine, and Patent Publication 2 discloses that a wound treating agent containing glutamine, polydexstrose, lactulose and befidobacteria is orally administrated to patients.
Referring to an external preparation and its administration method, Patent Publication 3 discloses that an external preparation containing either one of hydrophilic or white petrolatum and povidone iodine is coated on a wound surface. Also, Patent Publication 4 discloses that hydrogen-containing water is used as a liquid for external use in which a bedsore site is immersed, hydrogen-containing water is added dropwise onto the bedsore site and a coating means soaked with the hydrogen-containing water is affixed to the bedsore site. Further, Patent Publication 5 discloses that cotton gauze soaked with fradiomycin sulfate and trafermin is packed in the back of an ulcer. Furthermore, Patent Publication 6 discloses that a wound coating material composed of an unwoven fabric containing crosslinked hyaluronic acid, silver sulfadiazine and crosslinked alginic acid is applied to a wound surface.
On the other hand, hydrogen sulfide (H2S)-containing spa has been used for folk remedies from old, because it has been known to be efficacious against skin diseases or circulatory diseases. However, hydrogen sulfide (H2S) is difficult to handle on a daily basis thanks to its toxicity. In recent years, this hydrogen sulfide has been reported to have bioactivities such as cell protective action, blood vessel relaxing action, antioxidant action, neurotransmission regulation action and apoptosis inhibition action under low concentration conditions.
As such biological activities of hydrogen sulfide have been clearly understood, brisk trials of applying this to medical treatments are now under way.
For instance, Patent Publication 7 discloses that viablilty of mice is improved when they are exposed to a H2S atmosphere at 80 ppm to place them in “stasis conditions” where their activity is recovered.
Patent Publication 8 discloses a technical idea wherein a therapeutic gas having vasodilatory action such as hydrogen sulfide is stored in a biocompatible polymer matrix containing a polymer and closed cells and comprising a surface configured to come in direct contact with a wound site thereby delivering said therapeutic gas to said wound site.
As described above, various methods have so far been reported to treat wounds inclusive of bedsores, and various medical treatment methods harnessing the bioactivity of hydrogen sulfide are reported too. However, there is no report so far about curing a wound by exposing it to hydrogen sulfide or drawing hydrogen sulfide into lungs.
Accordingly, the present invention has for its object to provide a wound-treating gas composition and apparatus that is used with a novel wound-treating method making use of hydrogen sulfide.
As a result of various studies made for the purpose of achieving the aforesaid object, the present inventors have accomplished the present invention by finding that healing effect or efficacy of a wound is improved as the wound is exposed to a gas composition containing a constant amount of hydrogen sulfide or this gas composition is allowed to be inhaled in the living organism to be treated.
The first embodiment of the invention configured to achieve the aforesaid object provides a wound-treating gas composition containing hydrogen sulfide in a proportion of 20 ppm or lower.
The second embodiment of the invention configured to achieve the aforesaid object provides a wound-treating apparatus comprising a cover or container to receive the aforesaid wound-treating gas composition to expose a wound to the aforesaid gas composition and/or allow the living organism to be treated to inhale the aforesaid gas composition.
According to the invention disclosed herein, it is possible to provide a wound-treating gas composition and apparatus usable with a novel wound-treating method making use of hydrogen sulfide.
By way of example but not by way of limitation, the present invention is now explained in greater details with reference to one embodiment thereof.
The wound-treating gas composition according to the first embodiment of the invention (hereinafter called the “first embodiment”) contains hydrogen sulfide in a proportion of 20 ppm or lower.
The concentration of hydrogen sulfide in the gas composition to ensure that such a high therapeutic efficacy is obtainable is 20 ppm or lower. As the concentration of hydrogen sulfide is greater than 20 ppm, it gives rise to a decrease in therapeutic efficacy against wounds. Although the cause of this decrease has yet to be clarified, it would be related to the toxicity of hydrogen sulfide. The upper limit value to the concentration of hydrogen sulfide in the gas composition is preferably 10 ppm or lower at which there is wound healing efficacy obtained earlier, more preferably 5 ppm or lower, and most preferably 1 ppm or lower.
There is no lower limit value to the concentration of hydrogen sulfide as long as the gas composition contains hydrogen sulfide, but it is preferably at least 0.4 ppb, and more preferably at least 0.02 ppm in terms of healing acceleration.
It is here understood that the hydrogen sulfide concentration is given on a volume basis.
The gas composition according to the first embodiment is noticeably efficacious against wounds, in particular wounds difficult to heal over naturally, for instance, bedsores.
As shown in
Although the mechanism through which the aforesaid gas composition affects the treatment of wounds has yet to be clarified, it would be related to skin tissue changes by contact with the gas composition and improvements in the natural healing power caused by inhalation of the aforesaid gas composition. Therefore, it would be possible to boost up the healing of the wound noticeably if the aforesaid gas composition is fed to the cover or container 10 and a wound is exposed to hydrogen sulfide contained in the aforesaid gas composition and/or the living organism to be treated is allowed to inhale said hydrogen sulfide by the aforesaid apparatus construction.
The cover or container 10 used herein has a function of exposing a wound to the wound-treating gas composition, and a function of allowing the living organism to be treated to inhale said gas composition. The cover used herein is understood to refer to a member configured to cover a wound or the mouth or nose of the living organism to be treated, as exemplified by a shell-structured or sheet-shaped member. The container used herein is understood to stand for a member configured to take in a wound site or the mouth, nose or whole body of the living organism to be treated inside, as exemplified by a box-shaped member. There is no limitation on the material, structure, etc. of the cover or container 10 provided that they are incapable of reacting with hydrogen sulfide, and prevent a release of the hydrogen sulfide-containing gas around the apparatus. One example of the cover material includes hydrogenated styrene-base thermoplastic elastomer (SEBS), thermoplastic elastomer (TPE) or the like, and one example of the container material includes acrylic resin, glass or the like. The cover or container 10 may be made up of a plurality of materials. One example of the structure includes the one having an inlet and an outlet for the hydrogen sulfide-containing gas, the one constituted by a combination of plural members assembled by way of a gasket or the like, or the one having a door portion which the living organism to be treated goes in and out, and so on. The cover or container 10 is preferably a closable container in which the whole body of the living organism to be treated is taken or enclosed because it is easy to prevent the hydrogen sulfide-containing gas from leaking to the outside during use, and exposure to the delivered wound-treating gas composition and inhalation of said gas composition take place at the same time. In that case, it is more preferable to form the cover or container of a transparent material in such a way as to check the condition of the living organism during treatment.
The wound-treating gas composition fed into the cover or container 10 should contain hydrogen sulfide in a proportion of 20 ppm or lower, as mentioned above. Feeding of said wound-treating gas composition contributes to such noticeable wound healing efficacies as mentioned above.
The wound-treating apparatus 1 according to the present embodiment comprises a wound-treating gas source 20 to feed the aforesaid wound-treating gas composition to the cover or container 10. There is no limitation on the wound-treating gas source 20 with the proviso that it is capable of feeding the wound-treating gas containing no or little impurities in a stable way. A bomb loaded or filled with the wound-treating gas or a compound that reacts with components in the air to generate hydrogen sulfide may be referred to as an example.
The wound-treating apparatus 1 according to the present embodiment may further comprise a carrier gas source 30 configured to dilute the hydrogen sulfide-containing gas fed out of the wound-treating gas source 20 and boost up its delivery to the cover or container 10. There is no limitation on the carrier gas source 30 with the proviso that it is capable of stable carrier gas delivery. For instance, a bomb loaded with the carrier gas may be mentioned.
There is also no limitation on the type of carrier gas used herein with the proviso that it remains stable in the air and does not interfere with the wound healing action of hydrogen sulfide. As an example, air, nitrogen, argon and mixture thereof may be mentioned, among which air is preferred because it is easily available and because even when the whole body of the living organism to be treated is enclosed in the container 10, breathing is well ensured.
The wound-treating apparatus 1 according to the present embodiment is preferably configured such that gas delivery and interruption take place intermittently within a preset time. In one exemplary configuration, a flow rate control means such as a needle valve and a valve controller or mass flow controller may be provided in a pathway from the wound-treating gas source 20 to the cover or container 10. When the wound-treating apparatus 1 is provided with the carrier gas source 30 as described above, the aforesaid flow rate control means is also preferably located in the pathway from said carrier gas source 30 to the cover or container 10.
Other embodiment associated in technical idea with the present invention (hereafter called the “associated embodiment”) relates to an alternative wound-treating method comprising exposing a wound to the wound-treating gas composition according to the first embodiment and/or allowing the living organism to be treated to inhale said gas composition. According to said treating method, noticeable therapeutic effects on wounds are achievable by way of the action of the aforesaid wound-treating gas.
In the associated embodiment, there is no limitation on the means for exposing wounds to the wound-treating gas composition and/or allowing the living organism to be treated to inhale said gas composition; however, it is preferable to use the wound-treating apparatus according to the aforesaid second embodiment because the gas having a low hydrogen sulfide concentration can be fed in a stable manner.
The present invention will now be specifically explained on the basis of examples; however, these examples are given as an aid for an easy understanding of the present invention, but not by way of limitation.
In Example 1 as well as Examples 2 to 4 and Comparative Examples 1 and 2 to be given later, the efficacy of the invention against a bedsore model was studied.
A mouse (C57BL/6 mouse at 8 weeks old) was anesthetized by isoflurane, and its back skin was put and pressed between two strong magnets as shown in
<Exposure to the Hydrogen Sulfide-Containing Gas and/or Inhalation of Said Gas as Well as Observation of Bedsores>
The aforesaid mouse was placed in the container 10 of the wound-treating apparatus 1 constructed as shown in
The treatment according to Example 2, 3, and 4 was carried out as in Example 1 except that the concentrations of hydrogen sulfide in the gas fed into the container 10 were 10 ppm (Ex. 2), 3 ppm (Ex. 3), and 0.5 ppm (Ex. 4), respectively.
Referring to Example 2, photographs taken of the bedsore are attached hereto as
The treatment according to Comparative Example 1 was carried out as in Example 1 except that the gas fed into the container 10 was only an air, or a gas having a hydrogen sulfide concentration of 0 ppm.
Photographs taken of the bedsore are attached hereto as
The treatment according to Comparative Example 2 was carried out as in Example 1 except that the gas fed into the container 10 had a hydrogen sulfide concentration of 40 ppm.
Referring to Comparative Example 2, photographs taken of the bedsore are attached hereto as
From comparisons of
Referring to
The aforesaid results would imply that exposing bedsores to a gas containing hydrogen sulfide in a proportion of 20 ppm or lower and/or allowing the living organism to inhale said gas composition induce healing efficacy against bedsores. Especially when the concentration of hydrogen sulfide in the gas is set at 10 ppm or lower, noticeable healing efficacies would be obtained.
In Example 5 as well as Examples 6 and 7 and Comparative Example 3 to be given later, the effect of the invention on a skin excision model was examined.
One day after a mouse (C57BL/6 mouse at 8-weeks old) was preoperatively shaven off at its back, it was anesthetized by isoflurane to hollow out the back skin through the cuticle and the derma using a biopsy trepan (made by Kai Industries, Co., Ltd.) having a diameter of 6 mm.
<Exposure to the Hydrogen Sulfide-Containing Gas and/or Inhalation of Said Gas as Well as Observation of a Skin Excision>
After the aforesaid mouse was placed in the container 10 of the wound-treating apparatus 1 constructed as shown in
The treatments according to Examples 6 and 7 were carried out as in Example 5 except that the concentration of hydrogen sulfide in the gas fed into the container 10 was set at 10 ppm (Ex. 6), and 1 ppm (Ex. 7), respectively.
Referring to Example 6, photographs taken of the skin excision are attached hereto as
The treatment according to Comparative Example 3 was carried out as in Example 5 except that the gas fed into the container 10 was only an air, or a gas having a hydrogen sulfide concentration of 0 ppm. Photographs taken of the skin excision were attached hereto as
From comparisons of
The foregoing results would imply that the exposure to a gas containing hydrogen sulfide in a proportion of 20 ppm or lower and inhalation of said gas have a healing efficacy against not only bedsores but also general wounds.
In Example 8 as well as Comparative Example 4 to be given later, a diabetic mouse was used as the living organism to be treated to make a study of the inventive effect. As a diabetic living organism decreases in terms of wound natural healing power, some noticeable wound healing effect would be expected by exposure to the hydrogen sulfide gas and/or allowing the living organism to inhale said gas.
The treatment according to Example 6 was carried out as in Example 6 except that a diabetic mouse (C57BL/6J HamSlc-ob/ob mouse at 8-weeks old) was used as the living organism to be treated. Note here that the diabetic mouse used is an obese one as a model of type II diabetes.
Photographs taken of the skin excision are attached hereto as
The treatment according to Comparative Example 4 was carried out as in Comparative Example 3 except that the aforesaid diabetic mouse was used.
Photographs taken of the skin excision are attached hereto as
From comparisons of
The foregoing results would reveal that the exposure to a gas containing hydrogen sulfide in a proportion of 20 ppm or lower and/or inhalation of said gas are especially efficacious against living organisms whose natural healing power remains low due to diseases such as diabetes.
According to the present invention, it is possible to provide a novel method for treating wounds. The present invention is thus of great value in that the number of wound-treating options increase, and proper treatment is feasible depending on patient's conditions and constitutions as well as demands for treating methods.
| Number | Date | Country | Kind |
|---|---|---|---|
| 2019-122423 | Jun 2019 | JP | national |
| Filing Document | Filing Date | Country | Kind |
|---|---|---|---|
| PCT/JP2020/023342 | 6/15/2020 | WO | 00 |
