JP2002000716A - Covering material for granulation - Google Patents

Abstract

PROBLEM TO BE SOLVED: To obtain a covering material for granulation which is a matrix having sponge-like and foam-like many small void parts formed of bio- decomposable material having a large void part intended for granulation, and has characteristics of promoting granulation in the large void part, and quickly reconstructing granulation and a manufacturing method for the same. SOLUTION: This covering material for granulation is constituted by a porous matrix formed of bio-decomposable material composed of collagen, gelatin or a mixture thereof, having a large void part which is slit-like and shaped like a square pole, circular cylinder or elliptical cylinder and small void parts, of which the number is larger than that of the large void parts.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a coating material for granulation, which is used to regenerate tissue defects caused by intractable ulcers such as diabetic ulcer and pressure ulcer. More specifically, the present invention relates to a coating material for granulation, comprising a matrix of a biodegradable material having a large void portion for promoting granulation by attracting capillaries and cells to rapidly reconstruct a living tissue.

[0002]

2. Description of the Related Art Conventionally, treatment of intractable ulcers such as diabetic ulcers and pressure ulcers involves protecting the injured surface from the outside, maintaining a moist environment that promotes epidermis, and a pharmacological action that promotes epidermis itself. Many drugs have been used for granulation and the like. The difficulty of healing intractable ulcers is that the damaged ulcer surface is the base of the tissue that becomes the epidermis necessary for healing or the base for skin transplantation needed for treatment (tissue called granulation)
The main reason is that there is no.

At present, there are a small number of drugs and coating materials that claim that the main purpose is granulation. However, when a drug is used, it is necessary to apply it frequently to the damaged area before granulation actually occurs. In addition, the surface of the formed granulation becomes granular, so that the mother is not necessarily suitable for epidermis or skin transplantation. Not necessarily the floor.

[0004] In addition, in the case of a dressing material, since the wound surface is completely closed, exudate is easily stored, and bacteria are transferred to the stored exudate, causing infection to spread. Furthermore, there is a small amount of leachate stored, and there is a type of dressing that allows observation of the wound surface.However, since it is not biodegradable, it is expected that it will be removed after a certain period of time, or that it will be discharged naturally. The troubles remain. It can also cause significant pain to the patient, especially once the granulation has to be removed after it has become entangled in the fibers of the dressing.

Recently, a dermis defect graft made of collagen (so-called “artificial dermis”) has been applied to these intractable ulcers and has been found to have remarkable effects (plastic surgery, Vol. 39, No. 8). No., P779-787 (1996); skin,
Vol. 38, No. 3, P386-389 (1996). This is an attempt to use the tissue regeneration ability of the "artificial dermis" for granulation of intractable ulcers. However, if the "artificial dermis" is applied as it is, there is a drawback such as accumulation of exudate, and recently, exudate is drained by means such as finely tearing and packing, opening holes such as drain holes or slits ( Plastic Surgery, Vol. 39, No. 8, P779-787 (1996) However, it takes time and effort to cut fine, and "artificial dermis" sometimes has a silicone membrane on a collagen sponge. In many cases, when there is a drain hole, the granulation generated in the drain hole portion involves the silicone film and causes sticking, and in some cases, requires reoperation for removing the silicone film. In addition to the expensive raw materials, dermis is easily denatured and decomposed by physical and chemical treatments. Because there is,
Frequent use in the treatment of, for example, pressure ulcers may be economically difficult.

[0006]

As described above, in the conventional dressing for treating intractable ulcers, the exudate accumulates, and bacteria are transferred to the accumulated exudate, causing infection to spread. The applied coating had to be removed after a certain period of time.

[0007] Accordingly, the present invention is a dressing for treating intractable ulcers such as diabetic ulcers and pressure ulcers, wherein granules are formed on the damaged surface without accumulating exudate and removed after the objective is achieved by additional treatment. It is an object of the present invention to provide a coating material that can form a granulation without performing the treatment, can be treated at low cost, and can obtain a substance effective for treatment from the patient himself and can utilize it effectively.

[0008]

According to the present invention, there is provided a sponge-like or foam-like material made of a biodegradable material having a large void for the purpose of granulation. By using a matrix with small voids and attaching it to the damaged surface, the large voids open to the damaged surface promote the absorption of exudate while efficiently removing the body fluid from the large and small voids. (Including exudates and blood)
By actively attracting capillaries and cells into the large voids to promote the formation of granulation, as a result, the capillaries and cells are extended into the small voids to quickly reconstruct the granulation biological tissue. Achieved.

Specifically, the present invention provides a coating material for granulation comprising a porous matrix composed of a biodegradable material having large voids and a large number of small voids compared to the number of large voids. Is what you do. Further, the present invention provides a porous matrix made of a biodegradable material, wherein the large voids have a slit shape, a quadrangular prism, a cylindrical shape, or an elliptical cylindrical shape, and particularly the slit-like large voids have at least a thickness of the porous matrix. An object of the present invention is to provide a coating material for granulation formation, which has a longer diameter than that of the porous matrix, and further has a large void portion having an opening in at least one of the surfaces of the porous matrix. Further, the present invention provides
An object of the present invention is to provide a coating material for granulation formation, wherein the diameter of small voids in a porous matrix made of a biodegradable material is 5 μm or more and not more than the thickness of the porous matrix.

The present invention also provides a coating material for granulation, wherein the biodegradable material is a mixture of gelatin, collagen, saccharide, polylactic acid or polyglycolic acid, alone or as a mixture. The present invention provides a coating material for granulation, wherein the biodegradable material is composed of a mixture of gelatin and collagen.

[0011]

BEST MODE FOR CARRYING OUT THE INVENTION As the biodegradable material of the present invention, gelatin, collagen, saccharide, polylactic acid or polyglycolic acid can be used alone or as a mixture. The thing is gelatin. The main components of gelatin are almost the same as the constituent amino acids of collagen, which make up one third of the protein of living organisms. Therefore, there is little inconvenience in decomposing and absorbing in vivo. In addition, gelatin can withstand industrial production and can be obtained at a very low cost as compared with collagen. Actually, the gelatin used in the present invention is preferably a purified gelatin (for example, a purified gelatin listed in the Japanese Pharmacopoeia (so-called local gelatin)). Gelatin alone can constitute a biodegradable matrix encapsulating heterogeneous voids consisting of large voids and small voids.

However, the effect tends to decrease when water is absorbed at the damaged surface and expansion in the horizontal direction fills the large void. In terms of physical properties, gelatin alone is hard and brittle, and may be brittlely broken before use. Therefore, in the study of the present invention, a matrix having desired physical properties was obtained by mixing collagen with gelatin. As a result, excessive expansion is suppressed, the voids in the large voids as a place for granulation are secured, and the physical properties become more flexible. The water retention was also improved over gelatin alone. The change in physical properties is considered to be due to the fact that collagen, which is a rod-like polymer, contributes to maintaining the form as a skeleton. However, collagen is extremely expensive and gelatin is inexpensive, so the higher the gelatin ratio, the more cost-effective.

[0013] Sugars can be used as fillers in gelatin or gelatin-collagen mixtures. Since monosaccharides and disaccharides tend to flow out in a relatively short time after application to the damaged surface, and the effect of weight increase may be weakened, polysaccharides having higher molecular weights are candidates for the optimal weight increase. More preferably, use of a mucopolysaccharide having high affinity for gelatin (dermatan sulfate, chondroitin sulfate, heparin, hyaluronic acid, etc.) can be considered. Mucopolysaccharide and gelatin are easy to form a complex, and are therefore advantageous for shape retention.

On the other hand, polylactic acid or polyglycolic acid is a substance which can be used as a biodegradable material as inexpensive as gelatin. Recently, polylactic acid has been established in an industrial production system and can be mass-produced inexpensively. It can be solidified by foaming in the form of a solution. Further, similarly to ordinary plastics, it is also possible to obtain a porous body by dissolving with polyethylene glycol (PEG) or the like and eluted PEG by post-treatment.

[0015] A biodegradable matrix containing heterogeneous voids mainly composed of gelatin, polylactic acid, or polyglycolic acid,
Careful handling such as collagen which may be denatured or degraded is not always necessary. If necessary, use vacuum thermal dehydration, dry heat, γ-ray irradiation, ultraviolet irradiation, electron beam irradiation, X-ray irradiation, EOG, or any combination of these. Is possible. Among these methods, the γ-ray irradiation method and the EOG method can break intermolecular bonds and adsorb gas in the gelatin protein by each method. Is desirably cross-linked. The effect of granulation according to the present invention is not hindered by these sterilization treatments. The possibility of final sterilization is advantageous for reducing the number of steps, and is also considered to be advantageous for ensuring safety.

In the large void portion of the present invention mainly intended for granulation, the opening in at least one of the matrices needs to be in close contact with a wound, a defective tissue, or the like that requires some kind of tissue repair. The large void openings adsorb useful components in the exudate when the exudate is absorbed. This causes the capillaries and various cells to run up into the large voids, and granulation is formed in the large voids by the activity of these components. The large voids are
It has a shape that does not hinder the run-up of cells, and is preferably in the form of a slit, a square pillar, a cylinder, or an ellipsoid.

Among these shapes, the slit-like shape has an advantage that it can be opened and closed in a gap of an arbitrary size according to the area and shape of the damaged surface. In addition, it is preferable to provide a communication hole that connects the front surface and the back surface of the matrix with a straight line. In other words, by opening the slit and penetrating the opening, drainage of exudate is promoted, absorption of liquid components such as useful substances on the side of the hole increases, and the risk of infection due to accumulation of exudate is reduced. Also, observation of the wound surface becomes easy. However, if there is no major axis at least equal to the thickness of the matrix, a slit cannot be opened to form a void. Also, if the major axis of the slit exceeds the minor axis of the surface of the matrix, the matrix cannot be maintained in the form of maintaining the matrix around the void. Therefore, the major axis of the matrix surface (long side when the matrix surface is rectangular, The major axis of the slit must not exceed the diameter, or the major axis in the case of an ellipse).

As compared with the slit shape, the columnar structure such as a square column, a circular column, and an elliptical column has a drawback that the size of the gap cannot be adjusted, but it is easy to make a molded product by a method such as die cutting in advance. It has certain advantages. It is further advantageous to take the shape of the communication hole connecting the front surface and the back surface of the matrix with a straight line like the slit gap. The columnar structure may be tapered. In this case, it is advantageous in the order of parallel holes> a tapered hole having a large lower surface> a tapered hole having a large upper surface from the permeation state of the exudate visually. In the case of a large void portion having a columnar structure, if the diameter or the side is 1 mm or less in any shape, the exudate and blood components easily coagulate in the pore portion, and it is difficult to obtain an effective result. When the diameter or the side is 20 mm or more, when the pores communicate with each other, it does not become a large void portion in which granulation can be formed, and is similar to a mere open damaged surface.

In each case, if the hole diameter is small (open / closed state is small in the case of a slit), the capillary phenomenon is performed, and if the hole diameter is large (open / closed state is large in the case of a slit), absorption into a small void of a matrix around the hole is performed. With the assistance, blood vessels and cells run up and granulation is formed. These large voids do not necessarily have to have the same shape and size as long as they satisfy the above conditions, but if they have different shapes, they will cause unevenness to be formed in the granulation. . In that case, the shape may not be very recommended because there is a possibility that the skin becomes uneven or the grafted skin engrafts depending on the site.

These large voids are formed into slits by a mechanical device such as a skin graft mesher after producing a matrix body having small voids.
This mesher is very advantageous for obtaining a slit shape, and can be used at any timing after the matrix is prepared.

These large voids can be formed into various types of columnar structures by pouring them into a mold having the shape of the large voids before preparing a matrix body having the small voids. This method is advantageous for producing large voids (such as cylinders) that are not slits.

The small gap may have a continuous or independent bubble shape including a circular shape, an elliptical shape, and a deformed shape thereof, and may have a diameter at least smaller than that of the large gap. Its role is secondary to the last, and as described above, it absorbs and absorbs useful substances in exudates and blood components that are exposed to and pass through the inner wall of the large void, and Create an environment where blood vessels and cells can easily migrate. It is considered that the pore diameter should be at least smaller than the above-mentioned large void, but more preferably, the pore diameter should be at least a size that allows blood cell components to pass through and less than the thickness of the matrix. As long as the above range is satisfied, the pore size of the small void does not need to be uniform.

On the other hand, in a matrix having no small voids, the intended effect cannot be obtained because the components in the exudate do not adsorb from the walls of the large voids. The small voids are spongy, obtained by means of stirring and / or lyophilization,
Foam-like structures are preferred. Agitation involves the use of mechanical foaming equipment. At the time of stirring, a stirring method is appropriately selected mainly depending on the viscosity properties of the biodegradable material to be stirred.

On the other hand, freeze-drying is a conventional means for solidifying a liquid material. In order to sublimate ice crystals in the frozen liquid material to obtain a space as a small space, the pore size of the small space is ice. Depends on the degree of crystal growth. However, in the present invention, the variation of small voids due to the freezing step during the freeze-drying step, which affects the degree of crystal growth, does not affect granulation, and therefore, freeze-drying can be sufficiently performed by a normal method. There is no need to dare to make any settings.

The biodegradable matrix encapsulating different kinds of voids of the present invention has a film-like portion having no small voids on one surface thereof, or gradually becomes smaller as the size of the small voids becomes opposite to the film-like surface. It may have a structure with a sloped shape that increases. This is an effective means for preventing the escape of water, particularly when the material of the biodegradable matrix has low water retention. In order not to prevent the matrix from eventually being degraded and absorbed and become only self-organized,
The film or the layer having only a few holes is desirably a biodegradable material having the same components as those of the present invention.

[0026]

Hereinafter, the present invention will be described in more detail with reference to examples. (Example 1) Preparation of gelatin matrix containing heterogeneous void-encapsulated collagen Preparation of gelatin-collagen solution Purified gelatin powder (manufactured by Nacalai Tesque) in phosphate buffer
Was dissolved to prepare a 5 w / v% gelatin solution. Atelocollagen adjusted to 1 w / v% (manufactured by Koken Co., Ltd.)
0.1% acidic solution at room temperature with RO water and sodium hydroxide to a final concentration of 0.5 w / v%, pH 7-7.
5 and the gelatin solution prepared above was mixed at a weight ratio of 5:
The mixture was mixed at a ratio of 1 and uniformly dispersed to obtain a gelatin-collagen solution. The gelatin-collagen solution prepared in Preparation of the heterogeneous void inclusion matrix <400-200 type> is poured into an aluminum mold of 11 cm × 11 cm so that the gelatin / collage becomes 400 mg / collagen / 200 mg / mold and freeze-dried in vacuum. Thus, a matrix having small voids was obtained. The resulting matrix was subjected to a dry heat treatment at 180 ° C. for 1 hour to introduce crosslinking. Using a skin graft mesher (manufactured by Zimmer) for the matrix, an enlargement ratio of 1.5:
One slit-shaped large void (communication hole) was perforated to obtain a heterogeneous void inclusion matrix of the present invention.

(Example 2) Preparation of heterogeneous void inclusion matrix <foam 400-200 type> Purified gelatin powder (manufactured by Nacalai Tesque) was dissolved in RO water to prepare a 7.5 w / v% gelatin solution. An acidic solution of 37.5 g of 1% atelocollagen (manufactured by Koken Co., Ltd.) was treated with sodium hydroxide at room temperature at pH 7 to 7.5.
And 10 g of the gelatin solution prepared above was mixed to a final concentration of gelatin: 1.5 w / v%, collagen:
RO water was added to a concentration of 0.75 w / v% to prepare a gelatin-collagen solution. After foaming the obtained mixed solution at 5000 rpm for 3 minutes under ice cooling with a homogenizer,
Gelatin per mold: 400 mg, collagen: 200 m
Then, the mixture was poured into a mold having a predetermined shape so as to obtain g, and lyophilized, heat-treated and perforated by the method described in Example 1 to obtain a heterogeneous void inclusion matrix.

Example 3 Preparation of Heterogeneous Void Inclusion Matrix <Foam 400-100 Type> 18.75 g of a 0.1% acidic solution of 1% atelocollagen (manufactured by Koken Co., Ltd.) was used as a raw material, and the final concentration of gelatin was 1: 1. A gelatin-collagen solution was prepared so as to have a concentration of 0.5 w / v% and collagen: 0.375 w / v%, and different types were prepared in the same manner as in Example 2 except that the solution was poured into a mold so that the gelatin per mold was 400 mg and the collagen was 100 mg. A void inclusion matrix was prepared.

Example 4 Preparation of a Gelatin Matrix Encapsulating Different Kinds of Voids <Foamed Gelatin> A gelatin solution prepared to have a pH of 7 to 7.5 and a final concentration of 1.5 w / v% was cooled to 5000 by a homogenizer under ice-cooling.
After foaming for 3 minutes at rpm, gelatin per mold: 400
A heterogeneous void-encapsulating gelatin matrix was prepared in the same manner as in Example 2 except that the mixture was poured into a mold having a predetermined shape so as to obtain a mg.

Comparative Example 1 Preparation of Collagen Matrix Containing Heterogeneous Voids <Foamed Collagen> A collagen solution prepared to have a pH of 7 to 7.5 and a final concentration of 0.75 w / v% was cooled with an homogenizer under ice-cooling.
A heterogeneous void-encapsulated collagen matrix was prepared in the same manner as in Example 4, except that foaming was performed at 00 rpm for 3 minutes.

(Example 5) Granulogenesis-promoting effect of the product of the present invention in a rat skin defect model In order to confirm the effect of the product of the present invention on promoting tissue regeneration, it was applied to a rat skin defect model, and particularly its large voids. The granulation promotion effect in the part was examined. Sprague-Dawley female rats (200-300 g) were shaved on the back, and a full-thickness skin defect wound preserving 3 × 3 cm skin muscle was symmetrically placed across the midline.
It was surgically prepared using a scalpel. In this skin muscle-preserving full-thickness skin defect wound (hereinafter simply referred to as skin defect wound), the <400-200 type> according to Example 1 and the <foaming 400-200 type> according to Example 2 are slightly smaller than 3 × 3 cm. And pasted. In the present experiment, the width of the slit portion was expanded to 1.2 to 1.5 times for use.

At the time of application, a phenomenon was observed in which exudate was efficiently absorbed. Three days after application, red granulation tissue began to be observed in the large diamond-shaped voids formed during the expansion of each matrix, but the matrix around the large voids remained in the state at the time of application and remained. Seven days after application, granulation reached the upper side of the matrix. Seven days after application, the tissue was sacrificed and dissected to prepare a skin tissue specimen of the skin defect wound area, and the state of tissue formation was confirmed. Both matrices were found to regenerate tissues such as capillaries and fibroblasts in the large void. A large number of cells to be promoted were concentrated, and it was observed that blood vessels and cells had invaded the small voids of the matrix starting from the large voids. From these results, the <400-200 type> according to Example 1 and the <foaming 400-200 type> according to Example 2
Type>, it was confirmed that promotion of tissue regeneration, which is the object of the present invention, was achieved by granulation with a large void as a foothold. Also, no difference was observed between the freeze-dried product as a means for obtaining small voids and the foamed product in advance.

(Example 6) Effect of the components of the present invention on granulation in a rat skin defect model In order to confirm the effects of the components of the present invention on promoting tissue regeneration, the above-mentioned rat skin defect was examined. Using the model,
The granulation promoting effect was examined. In this study, <foamed gelatin> of Example 4 which is a single body of gelatin, <foamed collagen> of Comparative Example 1 which is a collagen alone, and <foamed 400-200 type> of Example 2 which is a complex of gelatin and collagen. Were compared. Since it is difficult to effectively produce a sponge having small voids by simply freeze-drying gelatin, <foamed gelatin> according to Example 4 which had been foamed in advance was used. All others similarly utilized foam.
According to the method of Example 5, the above-mentioned <
Expanded gelatin>, <Expanded collagen>, <Expanded 400-200
Type> was affixed, followed by observation and preparation of a skin tissue specimen. The result of <foaming 400-200 type> was as in Example 5. <Foamed gelatin>
The matrix around the large void remained, but <
Foaming 400-200 type> was deformed such as thinning and expansion. Seven days after the application, granulation was formed in the large void portion, but remained slightly below the upper side. The tissue formation state 7 days after application was such that a large number of cells such as capillaries and fibroblasts were concentrated in the large voids, but the invasion of blood vessels and cells into the small voids of the matrix was <foaming 400-200 type>. It was slightly inferior. However, the promotion of tissue regeneration, which is the object of the present invention, was considered to have been achieved to some extent. In <foamed collagen>, the edge of the large void was unclear three days after application. The formation of granulation in the large void 7 days after application was also poor. The tissue formation state 7 days after application is that the large voids are not clearly formed, the blood vessels and cells are diffusely dispersed, the granulation is not formed quantitatively, and the matrix is not spread into the small voids. Invasion of blood vessels and cells was also inferior to the other two types. From this, <foamed collagen> was deemed to be unsuitable for this purpose.

(Example 7) Effect of the composition ratio of the product of the present invention on granulation formation in a rat skin defect model The effect of the ratio of gelatin and collagen, which are the main components of the product of the present invention, on promotion of tissue regeneration will be confirmed. For 2
With respect to the composition ratio of the types, the granulation promoting effect was examined using the rat skin defect model described above. In the present study, the <foaming 400-200 type> of Example 2 and the <foaming 400-10 type> of Example 3 in which the collagen ratio was further reduced with respect to gelatin.
0 type> was compared. The result of <foaming 400-200 type> was as in Example 5. The result of <foaming 400-100 type> was almost equivalent to the result of <foaming 400-200 type> of Example 5. From this and the results of Example 6, it was determined that it was possible to obtain the desired result that gelatin was at least mixed with collagen.

(Example 8) Examination of the necessity of the constitution of the product of the present invention as a biodegradable material Compared with the <foamed 400-200 type> of Example 2, a commercially available foamed polyurethane sponge which is not biodegradable was used. Zimmer
Using a skin graft mesher, the evaluation of <urethane sponge> which is a large void formed by perforating a slit-shaped communication hole having a magnification of 1.5: 1 was experimentally examined in accordance with Example 5. The short-term evaluation result of <Foam 400-200 type> is Example 5.
It is like. After a month, the tissue was full of granulation and the original matrix had completely disappeared. In the <urethane sponge>, 3 days after application, the matrix around the large void was completely intact with the skin defect wound, but the exudate was well absorbed. In the tissue 7 days after application, invasion of blood vessels and cells was observed in the large void. One month later, the small voids were filled with blood vessels and cells, and granulation occurred.
The original matrix was completely left and adhered to the damaged surface, and the foreign body reaction was active. From this, it was found that non-biodegradable materials such as <urethane sponge> are not useful for tissue regeneration in the sense of repairing damaged tissue even if granulation is formed.

(Example 9) Examination of the mechanism by which the structure of the present invention having large and small voids induces granulation formation <400-200 type>, <foamed 400-200 type>, <foamed 40
0-100 type>

The tissue specimen 7 days after application according to the method of Example 5 was stained with Alcian Blue / PAS staining method for staining sugar. The <400-200 type>, <foamed 400-200 type>, and <foamed 400-100 type> are made without sugar at the time of preparation, so the part stained with sugar is a biological component (exudate, etc.) Is considered to be the result of infiltration. In all specimens, sugars are stained inside the matrix in a manner that follows the small voids in the matrix part, deriving from the large voids, and components such as exudate from the large voids are efficiently transferred to the small voids It was confirmed that it had penetrated into the water. It has been suggested that the shape in which the large voids are communicated with the many small voids promotes the penetration of useful substances such as exudates and the invasion of blood vessels and cells.

(Example 10) Examination that the product of the present invention is a material that can be subjected to EOG sterilization as final sterilization Except for performing wet EOG sterilization based on the Pharmacopoeia as the final sterilization, the <400-200 type of Example 1 is used. >, A heterogeneous void-encapsulated collagen matrix was prepared. Example 5
According to the method described above, the above is attached to the skin defect wound of the rat,
Follow-up observations and skin tissue specimens were prepared and examined. In the same manner as the <400-200 type> matrix of Example 1, the matrix treated at 180 ° C. for 1 hour and treated with EOG in Example 10 had good residual matrix around large voids 3 days after application. The formation of granulation in the large voids 7 days after application was also good.

(Example 11) Examination that the product of the present invention is a material which can be sterilized by γ-ray as final sterilization Dry heat treatment is performed at 180 ° C for 3 hours, and final sterilization is performed at 25 ° C.
<400-200 of Example 1 except that kGy γ-rays were irradiated.
Type>, a heterogeneous void-encapsulated collagen matrix was prepared. According to the method of Example 5, the above was applied to a skin defect wound of a rat, followed by follow-up observation and preparation of a skin tissue specimen, and examined. The heat treatment at 180 ° C. for 3 hours and the γ-ray sterilization matrix of Example 11 are the same as those of Example 1 <400-200.
As in the case of Type> Matrix, the matrix remained around the large void portion 3 days after application was good. The formation of granulation in the large voids 7 days after application was also good.

[0039]

As described in detail above, the present invention provides a porous matrix composed of a biodegradable material having large voids and a large number of small voids compared to the number of large voids for granulation. When used for the treatment of intractable ulcers such as diabetic ulcers and pressure ulcers, it can be used as a coating material to create granulation on the damaged surface without accumulating exudate. Granulation can be created without subsequent removal. In addition, a material that is inexpensive and effective for treatment can be provided. Furthermore, the coating material for granulation of the present invention can obtain a therapeutically effective substance from the patient's own exudate and can utilize it effectively, so that the therapeutic effect is significantly improved.

The coating material for granulation of the present invention promotes the absorption of exudate by the large voids opened to the damaged surface side, while efficiently excreting autologous body fluids (including exudate and blood) in large and small voids. By adsorbing and using the necessary substances, it actively attracts capillaries and cells into the large voids and promotes granulation, resulting in the spread of the capillaries and cells into the small voids and the granulation organism. It has excellent effects by quickly restructuring the organization.

 ──────────────────────────────────────────────────続 き Continuing on the front page (72) Inventor Keiji Ishikawa 1500 Inoguchi, Nakai-machi, Ashigara-kami, Kanagawa Prefecture Inside Terumo Corporation (72) Inventor Jun Konishi 1500 Inoguchi, Nakai-machi, Ashigara-gun, Kanagawa Prefecture Terumo Corporation F-term (reference) 4C081 AA12 AB19 BA16 CA151 CA171 CD011 CD121 CD151 DA02 DB03 DC12

Claims (6)

[Claims] A coating material for granulation comprising a porous matrix composed of a biodegradable material having a large void portion and a large number of small void portions compared to the number of large void portions. 2. The large void portion has a slit shape, the large void portion has a longer diameter than at least the thickness of the porous matrix, and the large void portion has an opening in at least one of the surfaces of the porous matrix. The coating material for granulation construction according to claim 1 which has. 3. The large gap portion according to claim 1, wherein said large gap portion has a shape of a cylinder, an elliptic cylinder or a quadrangular prism, and said large gap portion has an opening in at least one of the surfaces of the porous matrix. Coating material for granulation. 4. The method according to claim 1, wherein the diameter of the small gap is not less than 5 μm and not more than the thickness of the porous matrix.
Item 10. The coating material for forming granulation according to item 8. 5. The granulation method according to claim 1, wherein the biodegradable material is composed of gelatin, collagen, saccharide, polylactic acid or polyglycolic acid alone or in a mixture. For coating material. 6. The coating material according to claim 5, wherein the biodegradable material is composed of a mixture of gelatin and collagen.