JPH03286772A - Coating material for treating wound - Google Patents

Abstract

PURPOSE:To provide the coating material which has a pain expelling property, prohibits bleeding at the time of peeling and does not flaw a wound surface by applying a gelatin crosslinking type wound treating compsn. consisting of gelatin, a moisture retaining agent and a crosslinking agent on an adsorptive holder. CONSTITUTION:The gelatin crosslinking type wound treating compsn. consisting of the gelatin and the crosslinking agent thereof and the moisture retaining agent is applied on the adsorptive holder. Aldehydes, such as formaldehyde and glutaraldehyde, are usable as the crosslinking agent of the gelatin. Others, such as high-polymer compds. including active olefinic compds., etc., are used. Urethane sponge coated with 'Teflon(R)' is adequately used as the adsorptive holder to be used for the coating material. The coating material has the excellent properties to absorb water and to release the drugs to be used in combination therewith when treating drugs, such as dobramycin, generally used to prevent scald infections, are applied on this coating material and such coating material is used. In addition, this coating material prevents pains.

Description

Detailed Description of the Invention (Field of Industrial Application) The present invention provides a gelatin-crosslinked wound treatment composition comprising gelatin, a humectant, and a crosslinking agent, and a composition comprising gelatin, glutaraldehyde, and glycerin that retains adsorption properties. Burns, frostbite, etc. related to the coating material applied to the device and applied externally
The present invention provides dressings for treating skin ulcers, corrosive injuries, bedsores, etc.

(Prior art) Gelatin is non-antigenic, has excellent hemostatic properties, and has excellent absorbency for exudates, and has been released in sponge preparations (Sponzel), powder (Zelform), and film preparations (Zelfilm) [0 indicates trademark]. There is.

Skin defects, especially those caused by burns, can cause problems such as excessive body fluid loss and infection;
If it reaches 0%, life is at risk and it is necessary to immediately cover and protect the defective part.

Many studies have been conducted on artificial skin or wound dressings used to protect skin defects, and currently allogeneic skin pieces obtained from cadavers or living donors, processed animal skin,
Dressing materials using bio-derived collagen, gelatin polyisobutylene composites, gelatin polyethyleneimine composites, dressing materials using synthetic polymers (US Pat. No. 4,659,572)
No.) etc. are used.

However, the current state of injury treatment and burn treatment is that it is important to always accurately assess the condition of the wound surface and prevent infection, so it is important to apply ointment or cream containing an antibacterial agent and change the dressing frequently. It's mainstream.

(Problem that the invention sought to solve) Existing gelatin preparations are applied directly to the affected area and then covered with gauze, etc., but because they are non-crosslinked, they have poor adhesion and are susceptible to vibrations, etc. It has the disadvantage that it easily peels off.

Additionally, damage to the tissues that make up the skin generally causes sensory nerves to become hypersensitive. In the case of burns, the subcutaneous fatty tissue is damaged.In the case of third-degree burns, there is no sensitivity to pain;
For burns below the second degree that reach the dermal layer, the pain when applying the drug is unbearable for the patient. Causes of pain during and after burn treatment include mechanical stimulation from gauze,
Physical effects due to the ointment's water absorption, chemical irritation at pH 1, etc. are considered, but polyethylene glycol-based ointments containing antibacterial agents, which are commonly used, cause burning pain and dryness due to use. Problems such as bleeding and pain have been pointed out because the ointment and gauze stick to the wound surface.

(Means and effects for solving the problem) The present invention aims to develop a painless dressing for patients with skin injuries, especially for burn patients, and the present invention is directed to a dressing made by crosslinking gelatin with glutaraldehyde and preparing it together with glycerin. When tobramycin, which is commonly used to prevent burn infection, was applied to burn patients, it prevented pain and showed significant improvements in water absorption, tobramycin (concomitant drug) release, and therapeutic efficacy. It has been discovered that the coating material of the present invention has 1.4 to 1.5 times the elasticity, making it extremely suitable for use during exercise.

In addition, therapeutic agents that can be used in combination with the dressing of the present invention include antibiotics such as tobramycin, dibekacin sulfate, and micronomycin sulfate, as well as antibacterial agents such as ofloxacin, ciprofloxacin hydrochloride, and enoxacin, and semi-alkaline proteinase. Anti-inflammatory enzymes such as lysozyme chloride, anti-inflammatory analgesics such as indomethacin, sulindac, piroxicam, and loxoprofen sodium, hemostatic agents such as thrombin and sodium alginate, but when the pain is severe, local anesthetics such as propyroine and lidocaine are recommended. Furthermore, drugs effective for epithelial proliferation such as insulin and epidermal growth factor can be used.

Further, as a humectant used in the coating material of the present invention, glycerin, sorbitol, etc. can be used. As the crosslinking agent, aldehydes such as formaldehyde and glutaraldehyde, active olefin compounds, polymer compounds, etc. can be used.

(Effects of the Invention) The main purpose of the present invention is to provide pain relief to painful burn wounds by very flexible contact, to eliminate bleeding when the dressing is removed, and to enable treatment without damaging the wound surface. The present invention provides an inexpensive coating material with excellent drug release properties.

The present invention will be explained in more detail below with reference to examples (manufacturing examples, pharmacological test examples, and clinical test examples), but the present invention is not limited to the examples.

(Example) Production Example (1) Preparation of Reagents used a) Preparation of Glycerin Solution A To a 25% aqueous glycerin solution, 0.125% (final concentration) of methyl parahydroxybenzoate and 0.125% (final concentration) of propyl parahydroxybenzoate were added as preservatives. 0.063% (final concentration) and dissolved in a boiling aqueous solution, which was designated as glycerin solution A.

b) Preparation of gelatin solution B Add 2 g of gelatin, 3 ml of the above glycerin solution A, and 1.6 ml of water.
ml and 5% sodium hydrogen carbonate aqueous solution 4Hμm were added, stirred well, and heated in an autoclave at 120 degrees Celsius, 12 atmospheres, and 2
Sterilize for 0 minutes. This was kept at 60 degrees C in an incubator and used as gelatin solution B (11 ml).

C) Glutaraldehyde solution 3 ml of the above glycerin solution A, 1.44 ml of water and 400 μm of a 5% aqueous sodium bicarbonate solution are mixed and sterilized in an autoclave at 120 degrees Celsius and 2 atm for 20 minutes. The temperature was returned to room temperature, and 160 μm of a 25% glutaraldehyde aqueous solution was added in a sterile box to make 10 ml, which was kept at 60° C. in an incubator to form glutaraldehyde solution C.

(2) Operation Urethane sponge sheet reinforced with Teflon spray (
7x15cm) on a box-shaped plastic case, and add 10 ml of gelatin solution B and 10 ml of glutaraldehyde solution C.
+nl was added, stirred for 3 to 4 seconds, poured onto a sheet, and flattened to prepare a gelatin film with a thickness of 3fflrB. After standing in a sterile box for I hour, 1 ml of a 0.2% tobramycin-3.3% amino acid mixture (2 mg as h-bramycin) was applied onto the membrane using a Conlage rod to form a wound treatment dressing. To preserve this covering material, wrap the area around the case with vinyl tape or plastic wrap to prevent the lid from opening and store it in the refrigerator.

The plastic case was wiped with 70% alcohol absorbent cotton and sterilized with ultraviolet light for one night in a sterile box.
In addition, the urethane sponge sheet reinforced with Teflon spray was sterilized in an autoclave at 120 degrees Celsius and 2 atm for 20 minutes (see Figure 1). After removing the plastic case from the refrigerator and allowing it to come to room temperature, peel off the covering material by lifting up the urethane sponge sheets at both ends, cut off the unnecessary urethane sponge sheets, and apply it to the patient's wound.

Pharmacodynamics Test The amount of therapeutic drug (tobramycin) released from the coating material of the present invention and the change in weight over time during application were tested.

(1) Method a) Diffusion model method Flow-fbrough type related to skin absorption of drugs
The release model device of In1et, 1. Pharma
ce+rfics, 3Q, 35-45 (1986
Assembled according to the method described in 2007 (see drawing 2), fever ■
Sterilized freeze-dried pig dermis was used as a wound surface model by perfusing it with physiological saline. The samples were brought into contact with the coating material of the present invention for a predetermined period of time, and changes in weight and amount of tobramycin were measured.

b) Method using normal human skin A predetermined amount of the dressing of the present invention was applied to the inner side of a human upper arm for a predetermined period of time, and changes in the weight of the sample and the amount of tobramycin were measured over time.

For extraction of tobramycin, the sample was cut into pieces, 2.5 ml of water was added, stirred, and incubated at 37 degrees Celsius for 1 hour to allow swelling. After adding 2.5 ml of 5% trichloroacetic acid and stirring,
It was incubated at 7 degrees C for 1 hour. After that 5000t
pm, centrifuged for 10 minutes and collected the supernatant, which was used as a sample for tobramycin measurement. Tobramycin concentration was 5 ubst
rate Labcred Fluorescent
Immuno-assay (SLFIA, Ames
It was measured by TDA tobram7cin kit).

(2) Results a) In the method using the Di [usion model, the value was 22.7 ± 3.3 μg at 1 hour after the start of the release experiment, which was about the same as before the start, but about 19 μg during 6 hours.
It was found that most of the tobramycin contained in the dressing material was released. (Drawing 3) b) In the case of the method using normal human skin, there was no correlation between the concentration of tobramycin and the time after application, and there was a lot of variation, but 24 hours after application, I8,7 ± 4 ,7μg
This was a lower value compared to 22.8±3.6 μg before application. (Drawing 4) Also, regarding the weight change over time, in both cases of a) Dilfusion model and b) normal human skin, an equilibrium state is reached after about 6 hours, and in the former case, the weight change is about 1.7% compared to that before the release experiment. twice,
In the latter case, the change was approximately 0.4 times that before application. (Drawing 5) When placed on gauze moistened with distilled water, the swelling of the coating material of the present invention doubled after 4 hours, and 3 times after 24 hours.
．． It was found that it weighs six times as much.

(Drawing 6) The dressing material applied to the wound surface is water-absorbing and should further prevent leakage of exudate, but on the other hand, if it swells more than three times, it becomes extremely brittle, so dressings with such properties should not be used. considered inappropriate.

It has been found that the dressing of the present invention does not meet these conditions and is extremely suitable for wound protection.

Clinical trial Seven patients with degree I to ■ degree burns (including areas of degree ■) who were treated with tobramycin-polyethylene glycol ointment were partially treated with the dressing of the present invention, with their consent. An appropriate amount was applied depending on the size of the wound surface, covered with 3 to 5 pieces of gauze, and further covered with an elastic bandage. During the treatment, the condition of the dressing was observed and pain was investigated verbally at the waist.

Results All respondents answered that the product of the present invention did not cause any pain that was observed when applying tobramycin-polyethylene glycol ointment, whether during application, application, or peeling.

During peeling, gelatin remained on some of the sides, causing discomfort, but was gradually removed as epithelialization occurred.

No infection was observed, and epithelialization progressed faster than when treated with tobramycin-polyethylene glycol ointment and gauze. This is thought to be because there was no bleeding during ablation and the treatment could be performed without damaging the wound surface, which was effective for epithelialization.

It has been found that if epithelialization occurs quickly, the demarcation of the wound surface becomes clear and skin grafting surgery can be performed at an early stage, making it extremely useful for wound treatment.

[Brief explanation of drawings]

FIG. 1 shows the method for preparing the dressing according to the invention. FIG. 2 shows a flow-through type release model device. FIG. 3 shows the release progress of tobramycin from the dressing of the present invention in a flow-through type release model. FIG. 4 shows the release course of tobramycin when the dressing of the present invention is applied to human skin. FIG. 5 shows a flow-through type release model and the weight change over time of the dressing of the present invention on human skin. FIG. 6 shows the swelling change over time of the dressing of the present invention on water-containing gauze. Figure 2 Flow-thIough type release model device A Porcine dermis B MilliLap C Stirrer D Magnetic Stella E Physiological saline F Polyethylene tube G Specimen (l-bramycin pasted Invention coat FIN diameter 12 mm 1 1TIIcTO pump Incubator mlcIo pump 1 Invention Preparation method of coating material↓ 1ncuba+ionlor30mina160°Ct
51aliliZaFOn by autoclav
e Gelatin solution B (Hall Invention coating material am method Teflon treated urethane sponge (7 x 15 cm d 60 degrees C gelatin solution jIB (10 m) Invention lIl [lW material (tobramycin affixed) Invention coating material Time course of release of tobramycin of the present invention in a through-type release model when applied to human skin Time course of release of tobramycin from a dressing TOB: )-
Bramycin TOB/tobramycin time Figure 5 ov -through +7pe release model and human skin Figure Swelling change of the present invention dressing on water-containing gauze over time

Claims (4)

[Claims] (1) A wound treatment dressing in which a gelatin crosslinked wound treatment composition comprising gelatin, a humectant, and a crosslinking agent is applied to an absorbent holder. (2) The coating material according to claim 1, wherein the humectant is glycerin and the crosslinking agent is glutaraldehyde. (3) Claim 1: It is used for the treatment of wounds such as burns, frostbite, skin ulcers, corrosive injuries, bedsores, etc., and has an external patch form.
2. The covering material according to 2. (4) The covering material according to any one of claims 1 to 3, wherein the adsorbent holder is a urethane sponge treated with Teflon.