WO2002070550A1 - Fibroin powders and aqueous fibroin solutions for medical use - Google Patents

Abstract

Fibroin peptides having a molecular weight of 3500 or more and a molecular weight mode falling within the range of from 6000 to 15000, wherein, for example, part of the functional groups (α) in amino acids thereof have been condensed with a bifunctional compounds (β) carrying a carbon-carbon unsaturated group or a carboxyl group and having from 2 to 13 (preferably from 2 to 10) carbon atoms. These peptides are usable as medicinal base materials such as biological sealants and adhesion inhibitors.

Description

 Specification

Medical fibroin powder and aqueous fibroin solution

 The present invention relates to fibroin powder and fiproin aqueous solution that can be used in the medical field. Background art

 Silk fiber mouth-in is a protein with good biocompatibility, and thus has been conventionally used as a suture for surgical operations. In addition, fibrous mouth powder obtained by depolymerizing fibrous mouth into a peptide shows water solubility, and has been proposed or used in the field of food and cosmetics (for example, Japanese Patent Application Laid-Open No. 2000-2000). 4 8 2 8). Furthermore, in recent years, the use of fibroin other than sutures has been studied in the medical field (Japanese Patent Application Laid-Open Nos. 9-1192210 and 11-104422). In particular, they are required to be used as a sealant for adhering an incision or closing a wound after an operation, and as an anti-adhesion agent for preventing adhesion between organs.

However, in order to use it as a sealant or anti-adhesion agent, it is necessary to satisfy the condition that it can be applied to the human body surface and does not flow out. In order to satisfy this condition, the fibroin powder must be dissolved in water to produce a highly viscous aqueous solution. However, the conventional fiproin powder has a low molecular weight of the peptide, so that the viscosity does not increase even when dissolved in water. To increase the viscosity, it is necessary to dissolve a high-molecular-weight fibroin peptide, but the fibrous mouth inpeptide is very easy to gel because glycine and alanine are alternately arranged to form a j3 sheet structure. Therefore, when the molecular weight is high, it becomes insoluble in water. Therefore, it is not easy to obtain a viscous water-in-water solution. Therefore, an object of the present invention is to provide a fiproin powder and an aqueous solution of fiproin which can be used as medical substrates such as a sealing agent for a living body and an adhesion preventing agent. Disclosure of the invention

 In order to solve the problems, the medical fiber mouth powder for medical use of the present invention is characterized by comprising fibroin peptide having a molecular weight of 350 or more. When the molecular weight is less than 350, it was found that an appropriate viscosity was not obtained when dissolved in water, and that it was washed away even when applied to a living body. In addition, by setting the molecular weight to 350 or more, when a polymerizable functional group is added to the fibrous opening in-peptide, it polymerizes and gels, stays stably on the living body, and adheres and seals. This is because the property and the adhesion preventing property can be obtained.

 Preferably, the mode of the molecular weight of the fibroin peptide is in the range of 600-150.000. Those having a mode value within this range are extremely soluble in water, are suitable for a sealant for living organisms and an anti-adhesion agent, and have a stable and easy-to-use aqueous solution.

The fibroin peptide has a carbon number of 2 to 13, preferably a carbon number of 2 to 13 having a partial functional group (Q!) In an amino acid therein and a carbon-carbon unsaturated group or a carbonyl group. When condensed with the bifunctional compound () 8) of No. 5, the fibrous mouth peptide has polymerizability, gels by polymerization, and shows no toxicity to living organisms. Therefore, it is most suitable as a sealant for living body and an adhesion preventing agent. Particularly preferred compound (i3) is one having 2 to 10 carbon atoms. The bifunctional group of the bifunctional compound (/ 3) is one of a carbon-carbon unsaturated group or a carbonyl group used for polymerization, and the other is a partial functional group in the amino acid. It means a functional group used for condensation with (α). When the functional group (α) is in a serine residue, a threonine residue and / or a tyrosine residue It is a hydroxyl group, and the compound (J3) is preferably represented by the following general formula.

(In the formula, A is an atom or an atomic group that can be removed by condensation with a hydroxyl group, n is an integer of 0 or 10 or less, X and γ are a hydrogen atom or an alkyl group or a aryl group having 10 or less carbon atoms. And X and Y may be the same or different from each other, and the total of the number of carbons of X and the number of carbons of Y and n is 10 or less, preferably 7 or less.)

 In the process of producing the polymerizable fibroin peptide, the residue excluding the の of the compound (β), for example, an acryloyl group or a citrate group is selectively replaced with a hydroxyl group, leaving an amino group that activates lymphocytes. Because it can be stored.

In order to solve the above problems, the medical fibroin aqueous solution of the present invention has a fibroin peptide having a molecular weight of 3500 or more dissolved therein, and has a fibroin peptide concentration of 33% (w / w) or more. It is characterized. By control the molecular weight and concentration Thus, suitable methods of fabricating the Fuiburoin powder of _c the present invention comprising an aqueous solution having an optimum viscosity as a sealant or adhesion preventing agent, a silk fibroin in concentrated hydrochloric acid It is characterized by neutralizing and desalting after hydrolysis, removing substances having a molecular weight of less than 350 by dialysis, centrifuging the remaining solution, and freeze-drying the supernatant. A particularly important step in this process is hydrolysis with concentrated hydrochloric acid. As a result, silk fibroin becomes a water-soluble fibroin peptide having a molecular weight of tens of thousands or less. Sufficient hydrolysis does not occur with other acids or alkalis other than concentrated hydrochloric acid, resulting in poor recovery. The hydrolysis temperature is preferably from 40 to 80 ° C, and the treatment time is preferably from 5 minutes to 1 hour. The most preferred hydrolysis conditions are treatment with 12 N concentrated hydrochloric acid at 60 ° C. for 15 minutes. When hydrolysis is carried out under these conditions, a fibroin powder which is well soluble in water and whose aqueous solution has high viscosity can be obtained in high yield.

 In the present invention, the molecular weight of the five-mouthed peptide is determined as follows. First, the solution containing the fiber-in powder is fractionated by gel filtration, and the solution containing a marker with a known molecular weight is fractionated under the same conditions. Then, the absorbance of each fraction of those solutions is measured, and from the results, the molecular weight of the peptide contained in the fraction of the fibroin solution is estimated.

 In the present invention, the viscosity of the aqueous fibroin solution is measured at a temperature of 25 ° C. using a capillary-type automatic viscosity measuring device. BRIEF DESCRIPTION OF THE FIGURES

 FIG. 1 is a diagram showing the absorbance of the fibroin powder of the present invention. BEST MODE FOR CARRYING OUT THE INVENTION

Example 1

 The silkworm cocoons were cut into small pieces and boiled in 0.5% (W / V) aqueous ammonium bicarbonate for 40 minutes to remove sericin. After washing with warm water and air drying, a regenerated fiber mouth was obtained. Subsequently, fibroin powder was produced from regenerated fiproin by three methods, and these were designated as fibroin powders 1-3. The method for producing fiproin powder 13 is as follows.

Five mouth-in powder 1: In an eggplant-shaped flask, hydrolysis was carried out by adding 8 O ml of 12N concentrated hydrochloric acid to 50 g of regenerated fiproin and heating at 80 for 30 minutes. I got it. After hydrolysis, the mixture was diluted 4-fold with water and neutralized with 12 N sodium hydroxide. Thereafter, the resultant was dialyzed against running water for 4 days using a dialysis tube having a molecular weight of 1,000. The precipitate was removed by centrifugation using a centrifuge (HiTACH himac SC 20B) (8,000 rpm, 4 ° C, 40 minutes, the same conditions as in the following examples), and then lyophilized. did. As a result, 3.27 g (yield: 6.64%) of fibrous mouth powder 1 consisting of the fibrous mouth inpeptide was obtained.

 Fibroin powder 2: Produced in the same manner as fiproin powder 1 except that it was heated at 60 ° C for 15 minutes during hydrolysis, and a dialysis tube having a molecular weight cut of 350 was used during dialysis. As a result, 10.8 g (22% yield) of fibroin powder 2 composed of the fiproin peptide was obtained.

 Five mouth-in powder 3: Produced in the same manner as fibroin powder 1 except that it was heated at 40 for 15 minutes during hydrolysis, and a dialysis tube with a molecular weight cut of 1500 was used during dialysis. As a result, 17.5 g (yield: 35%) of fibroin powder 3 consisting of fibroin peptide was obtained.

 Next, it was examined whether fibroin powder 13 was soluble in water. When dissolved, the maximum concentration was determined. Furthermore, we investigated whether the saturated solution had such a high viscosity that it did not flow out even when applied to the human body surface.

As shown in Table 1, the fibroin powder 1 was soluble in water up to 70% (w / w), but had low viscosity. In addition, Five mouth-in powder 3 did not dissolve in water. On the other hand, the fiber mouth powder 2 was soluble in water up to 60% (w / w) and exhibited a sufficiently high viscosity. From this, it was found that the fiber mouth-in powder 2 can be used as a medical adhesive, a coating agent and an adhesion preventing agent. table 1 Funobuin no Mori no Ono • P 1

170% (w / w) low

 260% (w / w)

 3 insoluble

Example 2—

 The fibroin powder 113 obtained in Example 1 was added to a 0.3 M sodium chloride solution adjusted to pH 7.0 with 5 OmM phosphate buffer at 1% (W / V), 300 1 It melted so that it might become. Subsequently, the solution was subjected to gel filtration with a Cell mouth Fine GC L200 sf (0.9 × 100 cm) column, and fractionated into 0.5 ml per 0.5 ml test tube. These were eluted in the order of eluted fractions 1 to 120, and the absorbance was measured for each fraction. Similarly, the protein was also subjected to gel filtration and the absorbance was measured. Then, a calibration curve was prepared based on the results, and based on the calibration curve, the molecular weight of the fibrous opening in peptide contained in each fraction was estimated. Marker proteins include albumine egg (45kDa), chymotryps in (25kDa),

Lysozyme (14.3 kDa) was used.

FIG. 1 shows the results of the absorbance (wavelength: 28 O nm and 220 nm) of the fiber mouth powder 2. As can be seen in FIG. 1, the absorbance was high in fractions 88-101, all of which were 0.7 or more at a wavelength of 220 nm. Further, the molecular weight of fibroin peptide contained in fraction 88 was about 1500, and the molecular weight of fibroin peptide contained in fraction 101 was about 600. From this, it can be said that it is a main component of the fiber mouth powder 2 having a molecular weight of 600-150. Among them, the mode of molecular weight (fraction 95, The absorbance at a wavelength of 220 nm was 1.6 or more) was about 1000. Further, the mode of the molecular weight of the fibrous powder 1 was about 2000, and the mode of the molecular weight of the fibroin powder 3 was estimated to be 2000 or more. Example 3 —

 Fibroin powder 2 obtained in Example 1 was dissolved in water to have various concentrations. Then, the viscosity of each prepared aqueous solution was measured. The viscosity was measured under a temperature condition of 25: using a complete set of automatic viscosity measurement equipment (Shot Co., Germany, AVS-310). In addition, based on whether each aqueous solution did not flow out when applied to the surface of the human body, it was determined whether it was suitable as a medical adhesive, coating agent, or adhesion inhibitor.

As shown in Table 2, the aqueous solution in which fibroin powder 2 was dissolved at a concentration of 33% (w / w) or more was used as a medical sealant (adhesive, coating agent, etc.) and adhesion inhibitor. It was found to be suitable as Further, the viscosities of those aqueous solutions were 300 IMI ² / S or more. Table 2 Concentration (% (w / w)) Viscosity (Thigh ² / S) Judgment

9 1 4 .3 3 No

 1 7 2 0 .6 4

 2 8 6 7. 0 0

 3 1 1 9 3.1.8 1 No

 3 3 3 0 0 .0 0

 3 5 4 4 3 8. 1 7

 3 6 7 9 1 1. 3 5

Comparative Example 1

 In an eggplant-shaped flask, 20 g of 12 N acetic acid, formic acid, sulfuric acid or sodium hydroxide was added to 10 g of regenerated fiproin, and the mixture was heated at 60 ° C to attempt hydrolysis. After decomposition, the resultant was diluted 4-fold with water, neutralized with 12 N sodium hydroxide or hydrochloric acid, and dialyzed against running water for 4 days using a dialysis tube having a molecular weight of 350. After removing the precipitate by centrifugation, freeze-drying was performed to obtain a fibrous mouth in-peptide. As a result, acetic acid and formic acid did not hydrolyze for more than 30 minutes. It was not hydrolyzed even with sulfuric acid, and the amount of sulfuric acid was adjusted to 100 ml. However, the yield before concentration was 10%. Hydrolysis was carried out in 30 minutes with sodium hydroxide, but the amount of undecomposition was large, and the yield before concentration was only 3%.

Example 4

 [Acryloylation of water-soluble fibroin peptide]

Fibroin peptide produced under the same conditions as in fibroin powder 2 of Example 1 was dissolved in water under the same conditions as in Example 2. Then, an acryloyl group was introduced into the hydroxyl group of the serine residue in the fifty peptide by the following operation. Using a 300 ml eggplant-shaped flask, 1 g of the fibrous mouth in-peptide was suspended in 10 ml of dimethylformamide and cooled in an ice bath. After adding 1.37 ml of triethylamine to the suspension, 1.5 ml of acryloyl chloride diluted with 5 ml of N, N-dimethylformamide was added dropwise, and the suspension was placed in an ice bath. For 6 hours. To stop the reaction, 1.37 ml of triethylamine dissolved in 3.67 ml of dimethylformamide and 0.95 ml of 2-propanol were added, and the mixture was stirred in an ice bath for 20 minutes. . After the temperature of the reaction solution was returned to room temperature, it was dropped into 25 ml of water, and subsequently dialyzed against running water for 7 days with a dialysis tube having a molecular weight of 3500 cuts. After centrifugation, the supernatant was freeze-dried to obtain acryloylated fibroin peptide [Confirmation of acryloyl group introduction]

 Whether the acryloyl group could be introduced into the serine residue of the fibroin peptide by the above operation was confirmed by proton NMR (Brucker AC300) in the following manner. The acryloylated fiber mouth inpeptide obtained above was dissolved in 0.5 ml of heavy water so as to have a concentration of 2% (W / V) to obtain a measurement sample. The amount of acryloyl group introduced was calculated from the area ratio between the vinyl-bonded protons of the acryloyl group (5.8 ppm and 6.6 ppm) and the aromatic proton of the tyrosine residue (6.9 ppm and 7.2 ppm). As a result, it was found that an acryloyl group was introduced in an amount of 10 mol% with respect to one molecule of the fibroin peptide. This corresponds to the total amount of hydroxyl groups in serine residues.

 [Radical polymerization of acryloylated fiproin peptide]

In a 33% (W / W) or 50% (W / W) aqueous solution of acryloylated fibroin peptide (having acryloylated serine residue), 10 mo 1% based on acryloyl monomer. Then, ammonium persulfate and N, N, N ', N'-tetramethylethylenediamine dissolved in 0.1 lm 1 of distilled water were added as polymerization initiators. The reaction was carried out at room temperature for 15 minutes to polymerize the atariloylated fiproin peptide. The fibrous mouth peptide was gelled by the polymerization reaction. Finally, the gel was washed with water. [Measurement of gelation ratio and water swelling of gel]

 The dry weight (Ws) of the acryloylated fiproineptide before gelation and the weight (Ww and Wg) of the resulting gel at equilibrium water absorption and drying were measured, and the gels were obtained from the equations (1) and (2). The conversion ratio (GY: insolubilization ratio of acryloylated water-soluble fibroin peptide in dry weight) and the degree of water swelling of the gel (DS: ratio of equilibrium water absorption to dry weight of gel) were calculated.

 G Y (%) = Wg / WsXlOO (1)

 D S = (Ww-Wg) / Wg (2)

 As a result, the aqueous solution with 33% (W / W)% and 50% (W / W) aqueous solution had a GY of 20% and 45% and a DS of 7 and 3, respectively.

 [Biological experiment]

 The upper lung of the rat was excised, applied with an acryloylated fibrous mouth inpeptide, gelled, and examined for adhesion to the lung resection and biocompatibility. As a control, a commercially available polyethylene glycol paste (trade name: registered trademark “Adobasir”) was used. As a result, it was found that the acryloylated five-mouthed in-peptide had good biocompatibility and also had excellent adhesiveness.

 (1) Animals used

 Wistar rats weighing 250-300 g (about 10 weeks of age) (n = 5 in each group)

 (2) Anesthesia

After sedation with etren, 0.6 ml (100 mg / kg) of ketalal was administered intraperitoneally. Endotracheal intubation was performed under a microscope using an outer cylinder of a 16 G surflow needle. The respirator settings were N0 ₂ 1 L, 0 ₂ 1 L, tidal volume 3 m1, respiration rate 80 / min, and halothane was introduced and maintained at a concentration of 2% for inhalation anesthetic. The operation was stopped at the onset of chest closing, and pure oxygen ventilation was performed.

(3) Pre-operation operation The skin incision was shaved in the right lateral position, degreased with alcohol, and sterilized with isodine.

(4) Surgery operation

 The skin corresponding to the fifth intercostal space was incised with a messenger. The subcutaneous tissue was removed as much as possible, and the muscular layer was incised while stopping the bleeding with an electric scalpel to reach the chest wall. The fifth intercostal space was confirmed, and the chest was opened at the upper edge of the sixth rib. After ventilation was stopped, part of the lung was removed. Bleeding from the resected margin was cauterized with an electric scalpel. Acryloylated fibroin peptide or polyethylene dalicol glue was applied to the cut end, and visible light wavelength: 450-550 nm, light source: xenon light was irradiated for 5 minutes to polymerize each. A thoracic drain was inserted from between the open chest ribs to one below the ribs. After confirming that there was no bleeding and no residue, the chest was closed. After closing the chest, the chest drain was removed while applying pressure. The wound was disinfected with isodine and sprayed with furacene powder, and Novectoron spray was sprayed on it. After recovery from spontaneous respiration, the endotracheal tube was removed.

 (5) Evaluation

 After surgery, the animals were sacrificed on days 1, 4, 7, 14, and 21 and the presence of adhesion between the thoracotomy and the lung resection site was visually observed. Histological examination was performed by HE staining. As a result, there was no adhesion and the wound healing effect was better than that of polyethylene glycol paste. Example 5—

The same acryloylated fibroin peptide as in Example 4 was dissolved in previously degassed water to a fibroin concentration of 33% (W / W) or 50% (W / W), and water-soluble camphorquinone was added to this aqueous solution with acryloyl. It was added so as to be 11101% with respect to the monomer concentration. The mixture solution was irradiated with visible light for about 10 minutes at room temperature using Toxo Power Light (Visible light irradiator for dentistry manufactured by Tokuyama Corporation, wavelength: 400-52Οηπκ light source: halogen lamp) for about 10 minutes at room temperature. Polymerized fibroin peptide I let it. The fibroin peptide gelled by the polymerization reaction. After the reaction, the gel was washed with water. GY and DS were measured in the same manner as in Example 4. As a result, GY = 18 and DS = 7 were obtained by polymerization from a fiber mouth concentration of 44 (W / V¾). GY = 39 and DS = 4 were obtained by polymerization at a fiber mouth concentration of 63 (W / V%). Example 6—

 The same acryloylated fiproin peptide as in Example 4 was dissolved in previously degassed water to a fibrous mouth concentration of 50% (W / W), and the aqueous solution was adjusted to lmol% with respect to acryloyl monomer. After adding eosin Y as a photopolymerization initiator, ascorbic acid was added as a reducing agent so as to be 1/10 mol of eosin Y. Visible light with a wavelength of 450 to 550 nm was irradiated for 2 minutes at room temperature using a xenon lamp to polymerize the acryloylated fibroin peptide. The fiproin peptide gelled by the polymerization reaction. After the reaction, the gel was washed with water. When GY and DS were measured in the same manner as in Example 4, GY was 64% and DS was 3. Example 7—

 [Methacryloylation of water-soluble fibrin peptide] The carboxyl hemethacryloy group (methacryloy group) of dartamic acid residue and aspartic acid residue in water-soluble fibroin peptide was introduced by the following procedure. .

Fibroin powder was produced under the same conditions as in fibroin powder 2 of Example 1. Then, dissolve 10 times molar equivalent of WSC in the porphyrin powder lg in 20 ml of PBS (phosphate buffer saline), add the above fibroin powder lg, and adjust the pH to 7. It was kept near 0. After stirring at room temperature for 1 hour, 20 ml of ion-exchanged water was added to 1-ethyl-3- (3-dimethylaminopropylcarbodiimide). (Hereinafter referred to as “WS C”) and a solution of 2-Aminoetliyl methacrylate in an equivalent amount (prepared to pH 7.0 with 10% NaHCO ₃ ) were added dropwise at room temperature. . After stirring for 17 hours, the mixture was placed in a dialysis tube having a molecular weight of 3500 cuts, and dialyzed with running water for 3 days. After centrifugation, the supernatant was freeze-dried to obtain methacryloylated fibroin peptide.

 [Confirmation of introduction of methacryloyl group]

 It was confirmed by proton NMR (Brucker AC300) in the following manner whether the methacryloyl group (methacryloyl group) was able to be introduced into the lipoxyl group of the 5-peptide in-peptide by the above operation. The fibroin peptide obtained above was dissolved in 0.5 mL of heavy water to a concentration of 2% (W / V) to obtain a measurement sample. The amount of methacryloyl group introduced is based on the pi-bonded protons of the methacryloyl group (methacryloyl group) (5.8 ppm and 6.6 ppm) and the aromatic proton of the tyrosine residue (6.9 ppm and 7.2 ppm). Calculated from the area ratio of As a result, it was found that the methacryloyl group was introduced into all the hydroxyl groups contained in one molecule of fibroin peptide.

 [Photopolymerization of methacryloylated fibrous mouth peptide]

After adding eosin Y as a photopolymerization initiator to 50% (w / v) of the above methacryloylated fiproin peptide so that lmo 1% with respect to the acryloyl monomer, ascorbic acid is added as a reducing agent to eosin Y. Was added so that it became 1 110 mo 1. Visible light with a wavelength of 450-550 nm was irradiated for 2 minutes at room temperature using a xenon lamp to polymerize the acryloylated fiber-in-peptide. The fibroin peptide gelled by the polymerization reaction. Finally, the gel was washed with water. When the GY and DS of the gel were measured in the same manner as in Example 4, the GY was 23% and the DS was 7. Example 8-

[Water-soluble fibroin peptide C-esterification]

 By the following procedure, a cinnamate group was introduced into the hydroxyl group of the serine residue, threonine residue, and tyrosine residue in the water-soluble fibroin peptide.

 Fibroin powder was produced under the same conditions as in fibroin powder 2 of Example 1. Using a 300 ml eggplant-shaped flask, 1 g of the above fibroin powder was suspended in 10 ml of dimethylformamide and cooled in an ice bath. After adding 0.92 ml of triethylamine to the suspension, 2 g of cinnamate chloride dissolved in 5 ml of dimethylformamide was added dropwise, followed by stirring in an ice bath for 6 hours. To stop the reaction, 4.5-ml of dimethylformamide-dissolved 0-92 ml of triethylamine and 0.48 ml of 2-propanol were added, and the mixture was stirred in an ice bath for 30 minutes. After returning the reaction solution to room temperature, it was dropped into 20 ml of water, and subsequently dialyzed against running water for 7 days using a dialysis tube having a molecular weight of 3500 cuts. After centrifugation, the supernatant was freeze-dried to obtain a gay cinnamate esterified fibroin peptide.

 [Confirmation of introduction of C-cinnamate group]

The following procedure was confirmed by IR (JASCO) as to whether or not the cinnamate group could be introduced into the hydroxyl group of fibroin peptide by the above operation. A KBr disk prepared by mixing 2 mg of the fibroin peptide obtained above with 20 mg of KBr was used as a measurement sample. By comparing the measurement results of the unmodified fibroin peptide, the modified fibroin peptide, and the modified citrate, it was confirmed whether the citrate group was introduced. Before and after the modification, the absorption of 300-300 cm- ¹ from the benzene ring of the ca-cinnamate group was increased, confirming the introduction of the ca-cinnamate group.

 [Photopolymerization of Ca-cinnamic esterified fiproin peptide]

50% (W / V) aqueous solution of the obtained C-esterified fibroin peptide Was prepared and irradiated with ultraviolet light for 2 minutes at room temperature using a 500 W xenon lamp to polymerize the cis-esterified fibroin peptide. The fibroin peptide gelled by the polymerization reaction. Finally, the gel was washed with water. When GY and DS of the gel were measured in the same manner as in Example 4, GY = 26% and DS = 8. Industrial applicability

 ADVANTAGE OF THE INVENTION According to this invention, the fibroin powder and fibroin aqueous solution which can be used as a medical base material, such as a medical sealing agent and an adhesion preventing agent, can be obtained.

Claims

The scope of the claims  1. A medical fibroin powder comprising fibroin peptide having a molecular weight of 350 or more.  2. The medical fiproin powder according to claim 1, wherein the mode of the molecular weight of the fibroin peptide is in the range of 600 to 1500.  3. Said five-peptide in-peptide force A bifunctional compound having a carbon number of 2 to 13 having a partial functional group (α) in an amino acid therein and a carbon-carbon unsaturated group or a hepoxyl group () 3 3. The medical fibrin powder according to claim 1, wherein  4. The functional group (α) according to claim 3, wherein the functional group (α) is a hydroxyl group in a serine residue, a threonine residue, and / or a tyrosine residue, and the compound (i3) is represented by the following general formula. Medical fibroin powder.

(In the formula, A is an atom or an atomic group that can be removed by condensation with a hydroxyl group, n is an integer of 0 or 10 or less, X and Y are a hydrogen atom or an alkyl group or an aryl group having 10 or less carbon atoms. , X and Y may be the same or different from each other, and the sum of the carbon number of X, the carbon number of Y, and n is 10 or less.)  5. The medical fiproin powder according to claim 4, wherein the residue excluding A from the compound (/ 3) is an acryloyl group or a citrate ester group. 6. An organ healing comprising the medical fibroin powder according to any one of claims 11 to 5. Anti-wear agent.  7. A biological sealant comprising the medical fibroin powder according to claim 15.  8. A fibrin peptide aqueous solution having a molecular weight of 3500 or more is dissolved and the concentration of the fibrin peptide is 33% (w / w) or more. .  9. After hydrolyzing the silk fiber mouth with concentrated hydrochloric acid, neutralize and desalinate, remove substances with a molecular weight of less than 350 by dialysis, centrifuge the remaining solution, and freeze the supernatant. A method for producing medical fibroin powder, which is dried.