JP7199053B2 - Method for producing wound healing promoting solution - Google Patents

Description

TECHNICAL FIELD The technical field herein relates to a method of making a solution that promotes wound healing.

Plasma technology has applications in the fields of electricity, chemistry, and materials. In recent years, active research has been conducted on its application to medical care. Inside the plasma, ultraviolet rays and radicals are generated in addition to charged particles such as electrons and ions. It has been found that these have various effects on living tissue, including sterilization of living tissue.

For example, in Patent Document 1, by plasma irradiation, blood coagulation (see Example 4 of Patent Document 1, paragraphs [0063]-[0068]) and tissue sterilization (Example 5 of Patent Document 1, paragraph [0069] ]-[0074]) and leishmaniasis (see Example 6 of Patent Document 1, paragraphs [0075]-[0077]). It is also described that it has an effect of killing melanoma cells (malignant melanoma cells) (see Example 7, paragraph [0078] of Patent Document 1).

Further, Patent Document 2 discloses an antitumor aqueous solution that selectively kills cancer cells (see paragraphs [0085] to [0087] of Patent Document 2 and FIG. 16, etc.). This antitumor aqueous solution is an aqueous solution produced by irradiating a culture solution with atmospheric pressure plasma.

Japanese translation of PCT publication No. 2008-539007 WO2013/128905

However, in the conventional research and development, in the technical field of drugs that have the effect of promoting the healing of bedsores and wounds, plasma-based drugs have hardly been dealt with so far.

The technology of the present specification has been made to solve the problems of the conventional technology described above. That is, the object is to provide a method for producing a wound healing-promoting solution that has the effect of promoting the healing of pressure ulcers and wounds.

The method for producing a wound healing promoting solution in the first aspect comprises the step of irradiating an aqueous solution containing L-sodium lactate with plasma of a noble gas in an atmosphere purged with a noble gas.

The wound healing promoting solution produced by this production method promotes healing of pressure ulcers and wounds. That is, it speeds up the healing of the wound. In addition, the epithelialization rate of wounds in this wound healing accelerating solution is higher than in the past.

Provided herein is a method for producing a wound healing promoting solution that is effective in promoting the healing of bedsores and wounds.

It is a perspective view which shows schematic structure of a plasma processing apparatus. It is a perspective development view of the plasma irradiation part of a plasma processing apparatus. It is a perspective view of an intermediate block of a plasma processing apparatus. 3 is a perspective cross-sectional view for explaining a plasma gas supply system of the plasma processing apparatus; FIG. FIG. 1 is a diagram (part 1) for explaining a wounded part of a mouse in an experiment. FIG. 2 is a diagram (part 2) for explaining the wounded part of the mouse in the experiment. It is a figure which shows the observation procedure of the mouse|mouth in an experiment. It is a photograph which shows the progress of the wound part of the mouse|mouth in experiment. It is a photograph showing a wounded area after a certain number of days have passed since the wound. It is a graph which shows the area ratio of the wound part according to progress of days. 4 is a graph showing the rate of epithelialization of wounds over time. 1 is a graph showing the number of days until the epithelialization rate exceeds 30%. It is a graph which shows the shrinkage|contraction rate of the wound part according to days progress. 1 is a graph showing the number of days until a wound heals completely.

Hereinafter, specific embodiments will be described with reference to the drawings, taking a method for producing a wound healing acceleration solution as an example.

(First embodiment)
1. Apparatus for Producing Wound-Healing-Promoting Solution The wound-healing-promoting solution of the present embodiment is obtained by irradiating an aqueous solution containing L-sodium lactate with plasma. Therefore, first, the plasma processing apparatus, which is a manufacturing apparatus for the wound healing promoting solution, will be described.

1-1. Configuration of Plasma Processing Apparatus FIG. 1 is a perspective view showing a schematic configuration of a plasma processing apparatus 100. As shown in FIG. As shown in FIG. 1, the plasma processing apparatus 100 has a plasma generator 110 and a chamber 120 . The plasma generator 110 generates plasma. The chamber 120 is a reaction chamber for containing a container containing an aqueous solution and for controlling the atmosphere in which the aqueous solution is irradiated with plasma.

The chamber 120 is an irradiation room for irradiating the aqueous solution with plasma. The chamber 120 has an observation window 121 , a gas supply port 122 and a gas exhaust port 123 . The observation window 121 is a window for observing the state inside the chamber 120 . By using the observation window 121, it is possible to visually confirm the generation of plasma.

The gas supply port 122 is for supplying the atmosphere gas inside the chamber 120 . For example, Ar gas is supplied from the gas supply port 122 . As a result, the interior of the chamber 120 is filled with Ar gas. In this way, the atmosphere gas inside the chamber 120 can be controlled.

The gas outlet 123 is for discharging gas inside the chamber 120 .

FIG. 2 is a perspective developed view of the plasma irradiation unit 110 of the plasma processing apparatus 100. As shown in FIG. As shown in FIG. 2, the plasma irradiation section 110 has a first electrode 111a, a second electrode 111b, a cover case 112, an intermediate block 113, and a nozzle section .

The first electrode 111a and the second electrode 111b are an electrode pair. Plasma is generated by generating a discharge between the first electrode 111a and the second electrode 111b. The cover case 112 is an insulating case. The cover case 112 entirely covers the plasma irradiation section 110 . The intermediate block 113 is for enclosing the periphery of the first electrode 111a and the second electrode 111b and defining a space serving as a plasma generation region. The intermediate block 113 has a through hole 114 . The nozzle part 116 has a slit 117 for irradiating plasma.

FIG. 3 is a perspective view of the intermediate block 113 of the plasma processing apparatus 100. FIG. As shown in FIG. 3, the intermediate block 113 has recesses 115a, 115b, and 115c. The recess 115a is for covering the first electrode 111a without contact. The recess 115b is for covering the second electrode 111b without contact. The recessed portion 115c is a communicating portion for communicating the recessed portion 115a and the recessed portion 115b.

FIG. 4 is a perspective sectional view for explaining a plasma gas supply system of the plasma processing apparatus 100. As shown in FIG. As shown in FIG. 4, the plasma generator 110 has a first supply pipe 118a, a second supply pipe 118b, and a third supply pipe 119. As shown in FIG.

The first supply pipe 118a is for cooling the first electrode 111a. The second supply pipe 118b is for cooling the second electrode 111b. Therefore, the first supply pipe 118a and the second supply pipe 118b may supply rare gas such as Ar gas, for example.

The third supply pipe 119 is arranged between the first supply pipe 118a and the second supply pipe 118b. The third supply pipe 119 is for supplying plasma gas. A third supply pipe 119 supplies plasma gas to the space between the first electrode 111a and the second electrode 111b. The position to which the third supply pipe 119 supplies gas is, for example, the recess 115c of the intermediate block 113 .

1-2. Operation of Plasma Processing Apparatus First, while supplying gas for purging the chamber 120 to the gas supply port 122 , the gas inside the chamber 120 is exhausted from the gas exhaust port 123 . As a result, the interior of the chamber 120 is filled with the gas supplied from the gas supply port 122 .

Next, the first electrode 111a and the second electrode 111b are cooled while flowing Ar gas, for example, through the first supply pipe 118a and the second supply pipe 118b. In this state, the plasma gas is supplied from the third supply pipe 119 to the recess 115c of the intermediate block 113. As shown in FIG. Plasma gas is Ar gas, for example. Then, a high frequency voltage is applied between the first electrode 111a and the second electrode 11b. This causes a discharge between the first electrode 111a and the second electrode 111b. Thus, plasma is generated in the plasma generation region PG1 between the first electrode 111a and the second electrode 111b.

2. Method for Producing Wound-Healing-Promoting Solution The wound-healing-promoting solution of the present embodiment is a solution that promotes healing of wounds on the skin. This wound healing promoting solution is obtained by irradiating an aqueous solution containing L-sodium lactate with plasma. A method for preparing the wound healing promoting solution is described below.

2-1. Aqueous Solution Preparing Step First, an aqueous solution containing L-sodium lactate is prepared. Examples of this aqueous solution include Lactec (registered trademark). Lactec® contains sodium chloride, potassium chloride, calcium chloride and sodium L-lactate. The concentration of sodium chloride is 6.0 g/L. The concentration of potassium chloride is 0.3 g/L. The concentration of calcium chloride hydrate is 0.2 g/L. The concentration of L-sodium lactate is 3.1 g/L.

2-2. Plasma Irradiation Step Next, the aqueous solution containing L-sodium lactate is irradiated with plasma. At that time, only Ar gas is used as the plasma gas and the atmosphere gas. The interior of chamber 120 is purged with Ar gas. Therefore, almost no atmosphere-derived gas such as nitrogen gas or oxygen gas exists inside the chamber 120 . Then, plasma gas is supplied from the third supply pipe 119 to the recess 115c of the intermediate block 113 while flowing Ar gas, for example, through the first supply pipe 118a and the second supply pipe 118b. In this state, an AC voltage is applied between the first electrode 111a and the second electrode 111b. Thereby, a discharge is generated between the first electrode 111a and the second electrode 111b, and a plasma is generated between the first electrode 111a and the second electrode 111b. Thus, the aqueous solution is irradiated with plasma in an atmosphere purged with a noble gas.

The applied voltage is, for example, 1 kV or more and 10 kV or less. The frequency of the AC voltage is, for example, 10 kHz or more and 10 MHz or less. The irradiation distance between the liquid surface of the aqueous solution and the slit 117 of the nozzle portion 116 is, for example, 1 mm or more and 10 mm or less.

3. Effect of Wound Healing Promoting Solution The resulting solution is a Plasma Activated Lactec (PAL) aqueous solution (PAL). PAL has the effect of promoting self-healing of wounds by organisms.

In addition, the active ingredient is not necessarily clear. It is believed that some kind of active ingredient was generated by the reaction of the solute contained in the aqueous solution and the component derived from water with L-sodium lactate. However, it is not easy to isolate only the active ingredient from the aqueous solution. And it is by no means easy to specify the active ingredient itself. Since the interior of the chamber 120 is purged with Ar gas, particles derived from nitrogen atoms are hardly mixed into the aqueous solution.

4. Modification 4-1. Plasma Gas In this embodiment, the plasma gas and the purge gas are Ar gas. However, other noble gases such as He may be used.

(experiment)
1. Preparation of Aqueous Solution Two types of aqueous solutions were prepared. The two aqueous solutions are PAL (with plasma irradiation) and Lactec (without plasma irradiation). Lactec® contains sodium chloride, potassium chloride, calcium chloride and sodium L-lactate. The concentration of sodium chloride is 6.0 g/L. The concentration of potassium chloride is 0.3 g/L. The concentration of calcium chloride hydrate is 0.2 g/L. The concentration of L-sodium lactate is 3.1 g/L.

In irradiating the plasma, 10 mL of Lactec (registered trademark) was irradiated with the plasma. The irradiation distance was 4 mm. The irradiation time was 10 minutes.

2. Mice Diabetic mice (db/db mice) were used. Diabetic mice were male after 10 weeks of life.

3. Wound Formation As shown in FIG. 5, a circular wound was made in the mouse skin with a biopsy trepan of 8 mm diameter. As shown in FIG. 6, the surface of the wound was covered with a splint material, and the splint material was fixed to the mouse with glue and sutures. In addition, the fixation site was covered with a film dressing. As shown in FIG. 6, the wounds were formed on the left and right two locations in the area from the neck to the back of the mouse. The N number was 12 because 6 mice were used.

4. Experimental Procedure FIG. 7 is a diagram showing the experimental observation procedure. Mice were wounded on day 0 and wounded with either of the two aqueous solutions on day 1. When the aqueous solution was supplied, PAL was diluted 100 times, and Lactec (registered trademark) was used as it was without dilution. And evaluation was performed on the day shown in FIG.

5. Experimental Results FIG. 8 is a set of photographs showing the progress of wounds in mice. In FIG. 8, the notation PAL indicates wounds to which plasma-irradiated aqueous solution was administered, and the notation Ctrl indicates wounds to which Lactec (registered trademark) was administered without plasma irradiation. As shown in FIG. 8, the healing rate of wounds fed with PAL tends to be faster than that of wounds fed with Lactec®.

As shown in FIG. 9, when a certain number of days have passed since the wound, there are areas where the wound has healed in the peripheral area and areas where the wound still remains in the central area. Outside the healed wound area is an area of contracted skin. Inside the healed wound area is an epithelialized area. In humans, skin contraction hardly occurs.

FIG. 10 is a graph showing the area ratio of wounds over time. The wound area ratio is the ratio of the wound area to the area of a circle with a diameter of 8 mm. As shown in FIG. 10, the area ratio of the wound decreased as the days passed after the wound was formed. The rate of decrease in wound area percentage with PAL is faster than the rate of decrease in wound area percentage with Lactec®.

FIG. 11 is a graph showing the rate of epithelialization of wounds over time. The epithelialization rate of the wound site is the ratio of the area of the epithelialized region to the area of a circle with a diameter of 8 mm. As shown in FIG. 11, the epithelialization rate increases with the passage of days and saturates at a certain value. When PAL is used, the epithelialization rate saturates at around 50%. When Lactec (registered trademark) is used, the epithelialization rate saturates at about 45%.

As shown in FIG. 11, the rate of increase in epithelialization rate with PAL is slightly faster than the rate of increase in epithelialization rate without PAL. Moreover, the upper limit of the epithelialization rate when PAL is used is higher than the upper limit of the epithelialization rate when PAL is not used. The reason why the epithelialization rate saturates at a slightly low value is considered to be that a contracted region is generated in the wound as shown in FIG.

FIG. 12 is a graph showing the number of days until the epithelialization rate exceeds 30%. As shown in FIG. 12, the number of days for which the epithelialization rate exceeds 30% is about 7 days when PAL is used. The number of days when the epithelialization rate exceeds 30% is about 9 days when PAL is not used. Thus, it was revealed that the use of PAL accelerates the recovery of wounds.

FIG. 13 is a graph showing contraction rate of the wound over time. Wound contraction is the ratio of the area of the contracted area to the area of a circle with a diameter of 8 mm. As shown in FIG. 13, the rate of increase in wound contraction with PAL is slightly faster than the rate of increase in wound contraction without PAL.

FIG. 14 is a graph showing the number of days until the wound heals completely. As shown in FIG. 14, it took 16 days for the wound to heal completely with PAL. The number of days to complete wound healing without PAL is 20 days.

6. Summary of Experiments Wounds heal faster with PAL than without PAL. Moreover, as shown in FIG. 11, the epithelialization rate is higher when PAL is used than when PAL is not used.

(Appendix)
The method for producing a wound healing promoting solution in the first aspect has a step of irradiating an aqueous solution containing L-sodium lactate with plasma.

In the method for producing a wound healing accelerating solution according to the second aspect, in the plasma irradiation step, the aqueous solution is irradiated with plasma in an atmosphere purged with a noble gas.

In the method for producing a wound healing accelerating solution according to the third aspect, the aqueous solution contains sodium chloride, potassium chloride and calcium chloride.

DESCRIPTION OF SYMBOLS 100... Plasma processing apparatus 110... Plasma generation part 111a... 1st electrode 111b... 2nd electrode 112... Cover case 113... Intermediate block 116... Nozzle part 120... Chamber 121... Observation window 122... Gas supply port 123... Gas exhaust exit

Claims (3)

A method for producing a wound healing accelerating solution, comprising the step of irradiating an aqueous solution containing L-sodium lactate with plasma of a rare gas in an atmosphere purged with a rare gas. In the method for producing the wound healing promoting solution according to claim 1 ,
A method for producing a wound healing promoting solution, wherein the aqueous solution contains sodium chloride, potassium chloride, and calcium chloride. In the method for producing the wound healing promoting solution according to claim 1 or claim 2,
A method for producing a wound healing promoting solution, wherein the rare gas is Ar gas.

Images