JP5948687B1 - A biofilm for the purpose of promoting wound healing and covering (coaching) and protecting living organs. - Google Patents

Abstract

An object of the present invention is to form a coating film having both extremely thin water-repellent and degreasing properties on a wound surface and a damaged cell to cover the wound surface and the damaged cell and prevent leakage of intracellular fluid from the damaged cell. As a wound dressing that prevents spontaneous inflammation by preventing inflammatory reaction and promotes wound healing, and cell adhesion type coating on internal and external surfaces of various organs, and as a protective agent, by suture site, vascular anastomosis, laparotomy Provided is a biofilm for the purpose of suppressing intestinal edema associated with an inflammatory reaction and preventing adhesive ileus and the like. A biofilm agent comprising aluminum chloride, cyclodextrin, tannin (tannic acid) and water as main ingredients. Biological membrane comprising aluminum chloride in an amount of 0.01 to 25.0% by weight, cyclodextrin in an amount of 0.1 to 45% by weight and tannin (tannic acid) in an amount of 0.01 to 50.0% by weight with respect to 100 parts of water. Agent. A biofilm agent in which water as a main ingredient is water in body fluids (biological water such as sweat, tears, saliva, blood, gastric juice, etc.). [Selection figure] None

Description

Field of Invention

The present invention is an improved invention of application number 2014-246275, and forms a coating having extremely thin water-repellent and degreasing properties on the wound surface and the damaged cells, and coats the wound surface and the damaged cells, Wound dressing that relieves spontaneous pain and promotes wound healing by preventing leakage of intracellular fluid from impaired cells and preventing inflammatory response, and cell adhesion type coating for internal and external surfaces of various organs, and protection The present invention relates to an improved invention of a biofilm agent for the purpose of suppressing intestinal edema associated with an inflammatory reaction caused by a suture site, vascular anastomosis, laparotomy, and preventing adhesive ileus. For the purpose of covering and protecting the wound surface and various organs, various organ damage sites, and soft tissues such as muscle and fascia, periosteum and bone cortex, including aluminum chloride, cyclodextrin, water, In addition, by applying or spraying the biocoating agent of the present invention consisting of a plant-derived polyphenol compound, especially the commonly used name tannin (tannic acid), the rest and stability of the cell-adhesive coating are ensured, Realization of higher wound healing is possible.

Up to now, the wound coating agent, which has aluminum chloride, cyclodextrin and water as the main ingredients and has been developed as the main ingredient, application number 2014-246275 has been developed. There is a difficulty that it is difficult to keep rest from secondary external force that occurs in the course of friction caused by clothing and daily life. Each time the affected area rubs and bleeds, the pain of the affected area appears and the formation of scabs (scabs) causes damage to the wound that is difficult to predict. Further, there has been a demand for improvement in the physical strength of the coating agent, such as increased pigmentation, redness of scars (scars), and wrinkles such as irregularities.

By removing the factors that hinder the improvement of the texture with the surrounding skin, the wound healing power is optimized, and more easily, the skin is repaired in an inconspicuous state regardless of the prolonged healing period caused by the wound depth Is possible.

In order to maintain the toughness and stable film durability of the film of the wound film preparation of the invention of the previous application, a plant-derived polyphenol compound that acts to alleviate skin irritation, especially tannin (tannic acid) film Pay attention to sex. Furthermore, the present invention has been completed by focusing on a composite film that has an affinity with a film composition formed of aluminum chloride, cyclodextrin and water, does not inhibit the various effects of the invention of the prior application, and has a high synergistic effect. It was.

Problems to be solved by the invention

It is a plant-derived polyphenol compound, and the common name tannin (tannic acid) has the same kind of film water-repellent and astringent action as aluminum chloride and has a large molecular weight, so it has several hundred times the film effect of aluminum chloride. It has the function of forming a possible thick water-repellent coating. Furthermore, the film has a characteristic of forming a porous thin film with gas permeability such as water vapor, and has a coagulation action by binding to protein, so it is applied to the surface of skin, subcutaneous, fascia, muscle, periosteum, and bone cortex. By applying or spraying to the wound site by the interaction including aluminum chloride, cyclodextrin, tannin (tannic acid), and water, it has anticoagulant properties by suppressing fibrin production and damaged cells In addition, a three-dimensional microscopic water-repellent degreasing anti-inflammatory coating is formed on the cross section of the damaged cell, and in addition, there is an action of coagulating blood plasma protein and blood slightly exuding from the wound surface of the membrane. As a result, a strong crust-like film having a skeleton of xistrin tannin (tannic acid) is formed.

By forming this film, the anticoagulant / anti-inflammatory function is increased, and the stability of conventional biofilms is greatly improved and enhanced. A single skin-like film with a light skin tone is formed 30 minutes to 2 hours after application to the wound surface. That is, a strong composite film made of tannin (tannic acid) that cannot be obtained by the interaction with aluminum chloride, cyclodextrin, and water is formed. In addition, we focused on the buffering action of tannin (tannic acid), which relieves the feeling of irritation to the affected and wounded areas by aluminum chloride without depending on pH.

24 hours after application of the film, the composite film fuses with red blood cells on the wound surface to form a blood clot (blood scab), pain is remarkably reduced, and the affected area is opened without gauze. Dry wound management became possible even under the condition. Since a composite coating of aluminum chloride, cyclodextrin, and tannin (tannic acid) is also formed on the surface of the clot formed by continuous application of this agent, a stable coating can be obtained only once or twice daily. Maintenance can be continued, and the chance of secondary trauma at the wound site is also reduced, so that the rest of the affected area is maintained, and post-traumatic pigmentation after healing of the wound site or after scar healing can be greatly reduced.

In addition, the composite film made of aluminum chloride, cyclodextrin, and tannin (tannic acid) also forms a composite film at the boundary between the scab and the epidermis of the wound edge, so that the new epidermis and scab of the wound surface are formed. Even if a slight frictional force, tensile force, or shearing force is applied to the boundary portion of the skin, the effect of accelerating clot detachment can be obtained without damaging the new epidermis. The level difference between the wound surface and the surrounding skin after the clot has peeled depends on the depth of the wound, but the mild bumps that appear in the scar between 1 month and 1 to 2 years after the epidermis are not visible to the naked eye. .

This is because the composite coating formed by aluminum chloride, cyclodextrin, and tannin (tannic acid) works by suppressing and optimizing fibroblast overgrowth and collagen fiber overproduction, and is slightly raised The bulge of granulation tissue is formed by compression molding because it forms an early crust-like coating and a strong plate-like structure by early clot formation by the composite coating, and guards between both coatings with the granulation tissue surface Therefore, it is thought that it was possible to make the epidermal cells flat and new from the wound edge. In addition, aluminum chloride, cyclodextrin, and water prevent excessive inflammatory reaction, suppress UV rays, and prevent UV rays by tannin (tannic acid) early clot formation. Is reduced, and traumatic (inflammatory) pigmentation is suppressed, so that after wound healing, there is little difference in color with the surrounding skin, and wrinkles on the skin after trauma can be avoided significantly.

Means to solve the problem

Water is an essential component for constituting the biofilm agent, and the biofilm agent is constituted under the following conditions. The tannin concentration is within the range of 0.01 to 50% with respect to 100 g of purified water, considering aluminum chloride in the weight ratio of 0.1 to 25%, cyclodextrin in the range of 0.1 to 45%, and film thickness. Is preferably used. As the hydroxyaluminum salt, aluminum chloride can be used in anhydrous form or hydrate, but the effect is inferior, but it can also be used in polymers such as chlorohydroxyaluminum, alum and basic aluminum chloride.

For use in wound sites containing excess water (body fluid) such as blood leakage or exudate, a powdered dosage form is preferred, while forming a pseudo scab containing fine powder while adsorbing excess exudate, There is an advantage that more effective film formation is performed at a complicated interface with the wound portion. The fine powder is prepared by blending powders of aluminum chloride, cyclodextrin, and tannin (tannic acid), which are the main ingredients of the present invention, with a powder base auxiliary. Examples of the powder base auxiliary include starches such as silicic anhydride, chikarasu koji, corn starch, and phosphate processed starch, and other powders include zinc oxide and talc. By spray-drying a tannic acid-containing solution, such as inexpensive tannin (tannic acid), in advance, a fine powder with excellent fluidity, mixing and dispersibility, and water solubility can be obtained. These fine powders are particularly preferable in use, but pulverized fine powders such as pentaploid and gallic can also be used sufficiently.

The cyclodextrin (hereinafter referred to as CD) used in the present invention is an inclusion compound that can include hydrophobic substances such as sebum and emulsion by the interaction between aluminum chloride and water. , [Alpha] -CD, [beta] -CD, [gamma] -CD, and mixtures thereof, but derivatives thereof can also be used.

Among the polyphenol compounds, condensed tannin and hydrolyzable tannin can be used as tannin (tannic acid) with high film property. Peptides and cod powder or gallic, hydrolyzable tannins such as catechins of tannin and its gallic acid ester derivatives contained in tea leaves, leguminous tamarind tannin and mimosa tannin, and condensed tannins such as tea theaflavin and thealvidin Concentrates such as precursors can also be used, but there is a disadvantage that cost performance is low. Although the thickness and strength of the film tend to depend on the concentration, the tannin concentration is preferably 1 to 0.5 or less in terms of a weight ratio with respect to 100 g of water. is there.

The dosage form that can be used in the invention can also be blended into dosage forms such as powders, lotions, sprays, ointments, creams, tinctures and the like depending on applications. These dosage forms have the advantage that they can be applied and applied in sufficient amounts to penetrate the wound surface and surrounding skin.

Antibiotics, anticancer agents, immunosuppressive agents, antihistamines, steroidal and non-steroidal anti-inflammatory agents, moisturizing and thickening agents such as propylene glycol and glycerin, and normal viscosity agents as needed Can be used, but there are hydroxymethylcellulose, hydroxyethylcellulose, alginic acid, gelatin, water-soluble synthetic polymer compound, gums, etc., but since it precipitates depending on the concentration and mixing method, attention is paid to the blending amount and blending order.
Preferred <Example> and <Case> are described in detail below.

100 g of purified water was mixed with 15 g of aluminum chloride hexahydrate, 7.5 g of β-cyclodextrin, and 5 g of absolute ethanol, and 100 g of persimmon juice having a tannin concentration of 5% was added to obtain a yellow biofilm. .
As a <Case 1> according to this example, a 44-year-old male uses the left upper arm for scratching. Findings after 1 hour after injury (fig 1), sprayed with this coating agent, the composite film formed several minutes later (fig 2), and a thin scab after 24 hours (Fig3) is presented. This coating agent is sprayed twice a day (in the morning and after bathing) and dried. On the 15th day after performing this operation, the skin became clean and almost no pigmentation appeared (FIG. 4). fig4: Indicates 15 days after use.

Main agents 1 and 2 were dissolved in 500 g of purified water, then 3, 4, 5, 6, 7, and 8 were added and mixed by stirring to obtain a biofilm.
1. 45 g of aluminum chloride hexahydrate
2. β-CD 6.5 g
3. 100 g of persimmon juice (tannin concentration 5%)
4). Xanthan gum 1.5g
5. Glycerin 20g
6). 20g propylene glycol
7). 150 g of 10% sodium hydroxide solution
8). Absolute ethanol 10g
In this example, in order to suppress irritation caused by the acidity of aluminum chloride, a 10% sodium hydroxide solution was added to neutralize, and the resulting precipitate containing xanthan gum (including sodium chloride and aluminum hydroxide) was added. The persimmon astringent solution was added to the solution which was filtered and the pH was adjusted to 3.9 and mixed with stirring.
● A 39-year-old female as <Case 2> according to this example. An example of a prominent keloid caused by suppuration of left ear pinna cartilage. Images of the front surface of the left auricle (fig5) and the back surface of the left auricle before the operation (fig6) are presented. A part of the left auricular keloid was excised together with the auricular cartilage, full-thickness skin grafting was performed using keloid skin, and the rear surface was closed with sutures. This coating agent was applied after keloid resection, and after skin grafting and suturing. For wound care after the removal of the thread, this film agent was applied twice a day (morning and evening), and no other drugs were used. About one month after the operation, images of the front surface of the left auricle (FIG. 7) and the rear surface of the left auricle (FIG. 8) are presented. There is no recurrence of keloid, no post-inflammation pigmentation, and good color match with surrounding skin. fig5: preoperative (front of left auricle) fig6: preoperative (rear of the left auricle)

The main ingredients 1 and 2 were dissolved in 500 g of purified water, then 4, 5, and 6 were added. Finally, 3 was added and stirred and mixed to obtain a biofilm.
1. Aluminum chloride hexahydrate 60g
2. β-CD 5g
3. Strawberry astringent concentrate (tannin concentration, about 10%) 50g
3. Glycerin 20g
4). 20g propylene glycol
5. Absolute ethanol 15g

The main ingredients 1 and 2 were dissolved in 500 g of purified water, and then 4, 5, and 6 were added and mixed and stirred. Finally, 3 was added and mixed and stirred to obtain a biofilm.
1. Aluminum chloride hexahydrate 40g
2. α-CD 10g
3. 100g of gallic aqueous solution (tannin concentration 10%)
4). Glycerin 20g
5. 20g propylene glycol
6). Absolute ethanol 10g
● As <Case 4> according to this example, a 6-year-old boy falls at home, hits the left forehead against the corner of the desk, breaks the left forehead periosteum, breaks the periosteum on the forehead, and slightly in the bone cortex A wound with a wound depth was created. After local anesthesia and hemostasis with an electric scalpel, the film agent was sprayed into the wound, sutured, and then applied again to the skin at the sutured site. As a post-operative care, this film agent was continuously applied twice a day (morning and evening). The postoperative course is good, the whole thread is removed one week later, scarring is scarce one month after surgery, treatment with conventional disinfection and antibiotic ointment, and postoperative heparin-like substance promotes skin blood flow It leads to the formation of clean scars with less collagen stiffness and less stiffness than the method.

The main ingredients 1 and 2 were dissolved in 500 g of purified water, and then 4, 5, and 6 were added and mixed and stirred. Finally, 3 was added and mixed and stirred to obtain a biofilm.
1. Aluminum chloride hexahydrate 40g
2. γ-CD 5g
3. Strawberry concentrated tannin (tannin concentration 15%) 100g
4). Glycerin 20g
5. 20g propylene glycol
6). Absolute ethanol 10g
● A 66-year-old male as <Case 5> according to this example. An example of a ganglion produced on the right third dorsum. The ganglion was removed under local anesthesia, and after hemostasis with an electric scalpel, the film agent was sprayed in the wound and into the joint space of the open distal interphalangeal joint. Since the joint region of the distal interphalangeal joint is painful in the surrounding synovial membrane and difficult to close, the skin on the removed ganglion is removed, the epidermis is removed, and a dermal transplant is performed on the joint. It was again sprayed onto the transplanted dermis and the skin suture was closed. This skin agent was further applied to the skin suture site, and the operation was completed. Postoperative pain is very low, the postoperative course is good, and care is taken until the thread is removed. This film is applied twice a day (morning and evening), gauze and taping are performed. All yarns are steadily removed in 2 weeks. As a care after removal of the thread, it is applied twice a day (morning / night), 1 month after the operation, and the person who regularly runs and walks for a long time without recurrence of ganglion, sometimes the scar site is socks or Although there are occasions where the shoe rubs and bleeds, the scar is neither reddish nor stiff and remains inconspicuous.

させて、沈殿物を除いた溶液に戻し、次いで４、５を加えて撹拌して生体皮膜剤を得た。
１．塩化アルミニウム６水和物 １０ｇ
２．α−ＣＤ ５ｇ
３．柿渋（タンニン濃度５％） １００ｇ
４．グリセリン ２０ｇ
５．プロピレングリコール ２０ｇ
６．無水エタノール ５ｇDissolve main ingredients 1 and 2 in 100 ml of purified water and leave insoluble for 24 hours

Then, the solution was returned to the solution from which the precipitate was removed, then 4, 5 was added and stirred to obtain a biofilm.
1. Aluminum chloride hexahydrate 10g
2. α-CD 5g
3. Strawberry shibu (tannin concentration 5%) 100g
4). Glycerin 20g
5. 20g propylene glycol
6). Absolute ethanol 5g

10 g of aluminum chloride hexahydrate, 10 g of β-CD, and 10 g of spray dried fine powder of persimmon tannin are introduced into a ceramic ball mill and mixed and ground for about 30 minutes with respect to 100 g of the powder base auxiliary agent. The powdered biological film agent of 100 mesh pass was obtained by mixing and pulverizing the moisture-absorbing block powder of aluminum chloride with the powder base auxiliary agent. The powder base auxiliary was produced by blending 40 g of zinc white, 40 g of talc, 20 g of corn starch starch, and 5 g of anhydrous silicic acid.

Powder base auxiliary agent 100g, main ingredient aluminum chloride hexahydrate 15g, γ-CD 8g are introduced into a porcelain ball mill and pulverized for about 25 minutes. An agent was obtained. The powder base auxiliary was produced by blending 40 g of active zinc, 40 g of talc, 20 g of corn starch starch, and 5 g of anhydrous silicic acid fine powder.

Effect of the invention

Abrasion of skin, cutaneous wounds, cuts, wound management of wounds, scab formation, epidermis, covering the skin, subcutaneous tissue, fascia, muscle, cartilage, periosteum, and bone. Early, causing traumatic pigmentation and scarring of the skin to become less noticeable early.

Reduction of acute inflammatory reaction (swelling, edema, pain) at the time of open fracture, suppression of persistent inflammatory reaction, prevention of necrosis of muscle and bone tissue and ossification due to secondary infection, called lower limb amputation It works to avoid the last resort.

In the case of severe burns, if the pain is managed or if intravenous anesthesia can be performed, spray or powder sprayer etc. on the whole body skin under the conditions and conditions to suppress or adsorb a large amount of exudate By doing so, deterioration of the general condition can be suppressed. The porous capsule structure does not interfere with the formation of capillaries and the formation of granulation tissue with collagen fibers, thus increasing the rate of transplantation and the formation of keloids and hypertrophic scars in the transplanted skin and skin skin wound. Therefore, it is possible to form beautiful and stretchable skin.

In the burned side of the fingers and toes, and in the burnt of the lower jaw neck, the composite film of the present application acts to suppress the inflammatory reaction because of the three-dimensional coating of damaged cells, and suppresses fibroblast activity and is excessive. As a result of suppressing epithelial growth of collagen fibers and completing the epidermis while the plate-like clot formed earlier by the composite film compresses and shapes the granulation tissue bulge formed on the wound surface over time, The shortest and appropriate wound healing process can be guided to prevent scar contracture, and there is an advantage that it can be used safely before and after surgery in procedures such as skin transplantation, and anti-inflammatory and capsule effects are avoided from pain and secondary infection. Promotes epidermalization of shallow burn areas that do not require skin transplantation, increases the rate of transplanted skin, and prevents the formation of keloids and hypertrophic scars on the transplanted skin and skin skin wounds. With elastic skin formation The ability.

Suppresses fibroblast activity and suppresses excessive collagen fiber growth by suppressing the avoidance of inflammatory response by three-dimensional coaching of damaged cells in the burned side of fingers and toes, and mandibular neck By leading to an appropriate wound healing process, scar contracture is prevented, dysfunctions such as flexure contracture and extension restriction, and behavioral disorders are avoided, and skin wrinkles are avoided.

Prevent suture failure in digestive tract, hepatobiliary system, respiratory system, gynecological surgery. Shorten the period of appearance of inflammatory edema after surgery, shorten hospital stays, and speed up rehabilitation. However, in the use for the cardiovascular system and the use for vascular anastomosis, the tannin (tannic acid) concentration and the application conditions may be considered to cause thrombus formation.

As a local treatment for cancer, anticancer drugs (anticancer drugs) are mixed and applied to or spread on the main lesions or sites of metastatic cancer to cover the cancer lesions and prevent disseminated metastasis, as well as cancer. It is possible to achieve a reduction effect. Since it can be used easily in various organ tissues in the body including cancer cells, and it does not cause any adverse effects even if left behind, it is an alternative means that is effective for current cancer treatment and can be implemented at low cost.

Claims (5)

Covers and protects the wound surface and organs of the skin and subcutaneous tissues, the site of organ damage, and the wound surface reaching the periosteum and bone cortex, the main ingredients include aluminum chloride, cyclodextrin, tannin (tannic acid) and water A biofilm agent that is intended to coat damaged cells. The biofilm agent according to claim 1, wherein the concentration of aluminum chloride is 0.01 to 25.0 wt% with respect to 100 parts of water. The biofilm agent according to claim 1, wherein the cyclodextrin concentration is in the range of 0.1 to 45% by weight with respect to 100 parts of water. The biofilm agent according to claim 1, wherein the concentration of tannin (tannic acid) is 0.01 to 50.0 wt% with respect to 100 parts of water. The main ingredient is water in body fluids (sweat, nasal discharge, tears, saliva, trachea and bronchial secretions, blood, inflammatory exudate, gastric mucus and gastric juice, small intestinal mucus, pleural effusion, lining fluid, retroperitoneal organs 2. Powdered biological coating agent according to claim 1, which is water that moisturizes the surface, water of the mediastinum, water that moisturizes the large blood vessels, cervical mucus, vaginal secretion, anal gland secretion, etc.