JP2002363083A - Aerosol preparation for covering wounded surface - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide an aerosol preparation for covering a wounded surface in a small attaching amount, and further capable of making clear whether the wounded surface is appropriately covered or not by eyesight. SOLUTION: This aerosol preparation is obtained by filling a very fine particle state material of a low molecular weighted and regenerated chitosan having 10,000-200,000 average molecular weight, 1.0-11.0 μm mean particle diameter in its dry state and 0.50-1.35 coefficient for variation of the particle diameter, into a container together with a dispersing solution and a propellant, and also the aerosol preparation for covering the wounded surface is obtained by coloring the very fine particle state material of the low molecular weighted and regenerated chitosan with a coloring agent.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to an aerosol, and more particularly, to an aerosol using microparticles of regenerated low molecular weight chitosan, which is capable of covering a wound surface with a small amount of adhesion. The present invention relates to an aerosol agent for covering a wound surface, which has a coating effect, allows the coating range to be clearly confirmed by visual observation, and is suitable for adhering an arbitrary amount of adhesion.

[0002]

2. Description of the Related Art Japanese Unexamined Patent Publication No. 9-328432 discloses a spray containing chitin and a propellant in an aerosol container as a spray having a hemostatic effect, an anti-inflammatory effect and a wound healing effect. Chitin used in the spray is fine powder, granules, beads and fibers, and the particle size is 1 to 500 mesh, preferably 30 to 300 mesh, more preferably 100 mesh.
The powder passing through a mesh of ~ 250 mesh is used together with the propellant in a pressure-resistant container having a nozzle for injection. However, the spray described in this publication has various disadvantages due to the large particles of chitin contained in the spray.

[0003]

SUMMARY OF THE INVENTION In order to overcome the drawbacks of the conventional spraying agent using chitin particles, the present invention uses a low-molecular-weight regenerated chitosan to make chitosan into fine particles, By defining the average particle diameter of the body, the coefficient of variation of the particle diameter distribution, and the average molecular weight, the aerosol is sprayed on wounds such as cuts, abrasions, exfoliated wounds, cut wounds, and wounds such as surgery. The purpose of the present invention is to provide a wound surface covering aerosol agent capable of covering a wound surface with a small amount of adherence when adhered, and further visually inspect whether the wound portion is appropriately covered. It is intended to provide an aerosol agent for a wound surface coating agent using low molecular weight regenerated chitosan microparticles which can be clearly confirmed.

[0004]

SUMMARY OF THE INVENTION The present invention relates to a low molecular weight regenerated chitosan having an average molecular weight of 10,000 to 200,000 and an average particle diameter of 1.0 to 11.0 μm when dried.
m, an aerosol for covering a wound surface, in which a microparticle having a variation coefficient of particle diameter distribution of 0.50 to 1.35 is filled in a container together with a dispersion solution and a propellant. It is an aerosol for covering a wound surface, in which a granular material is colored with a coloring agent.

[0005]

BEST MODE FOR CARRYING OUT THE INVENTION Chitosan used in the present invention is obtained by deacetylating chitin obtained from crustaceans and insects with an aqueous alkali solution or the like to obtain chitosan. Instead of granules, this chitosan is dissolved in an acidic aqueous solution to form a chitosan acidic aqueous solution, which is a regenerated chitosan that has been coagulated and regenerated in a basic aqueous solution. It is a low molecular weight regenerated chitosan obtained by decomposition. By reducing the molecular weight of chitosan and coagulating and regenerating, chitosan can increase moisture absorption and release when used as a spray agent of the present invention as fine particles.

[0006] Low molecular weight chitosan can be obtained by heat-treating chitosan in an aqueous solution of sodium perborate, and the degree of deacetylation of chitosan used at this time is particularly problematic as long as it can be dissolved in an acidic solution. However, those having a degree of deacetylation in the range of 60 to 100% are preferred.

As the acid used for dissolving the low molecular weight chitosan, for example, acetic acid, dichloroacetic acid, formic acid or the like can be used alone or in a mixture, and the concentration of the acidic aqueous solution is not particularly limited. What is necessary is just to be the range which chitosan melt | dissolves.

[0008] The low molecular weight chitosan acidic aqueous solution is coagulated and regenerated in a basic aqueous solution to obtain a low molecular weight regenerated chitosan. At this time, the composition of the basic aqueous solution is determined when pulverizing the regenerated and coagulated low molecular weight regenerated chitosan. A state in which a suspension is easily converted into a milky liquid, that is, a brittle low molecular weight regenerated chitosan coagulate is preferably obtained. For example, an aqueous solution of ammonia, ethylenediamine, sodium hydroxide, or the like,
Alternatively, even when a polar alcohol such as methanol or ethanol is added to this basic aqueous solution,
Salts such as sodium acetate and potassium acetate may be appropriately added.

The low-molecular-weight regenerated chitosan solidified and regenerated in a basic aqueous solution is sufficiently washed with water until neutral, and then pulverized, dispersed, and refined in water with a homogenizer or the like to form a milky suspension. The suspension is discharged and dried in a high-temperature atmosphere together with pressurized air to obtain regenerated chitosan fine particles having a reduced molecular weight. The resulting regenerated chitosan microparticles having a reduced molecular weight may be used as they are, or may be further pulverized using an air-flow type collision pulverizer or the like to make them finer. In addition, the obtained low molecular weight regenerated chitosan fine particles may be used for classification, and at this time, there is no particular limitation on machinery used for classification, for example, an air classifier, a sieve classifier, and the like. Can be used.

The average molecular weight of the low molecular weight regenerated chitosan used in the present invention is preferably in the range of 10,000 to 200,000. Those having an average molecular weight of more than 200,000 are not preferred because they have a small diameter expansion coefficient when wet and cannot cover the wound surface with a small amount of adhesion. Average molecular weight is 1
Those having a molecular weight of less than 000 are not preferable because they are soluble in water, so that even if they are attached to the wound surface, they dissolve in the exudate in the body and cannot sufficiently cover the wound surface.

The average particle diameter of the dried low molecular weight regenerated chitosan fine granules used in the aerosol preparation is 1.0 to 11.
An average particle diameter in the range of 0 μm, preferably in the range of 3.0 to 7.0 μm is suitable. In addition, the average particle diameter referred to in the present invention is a geometric mean of diameters in terms of volume. If the average particle diameter when dried is larger than 11.0 μm, it is not preferable because it absorbs exudate from the body, has a small diameter expansion coefficient when wet, and it is difficult to coat the wound surface with a small amount of adhesion. On the other hand, when the diameter is smaller than 1.0 μm, the content floats in the air and scatters when sprayed as an aerosol agent to cover the wound surface, and it is not preferable because the target wound surface cannot be covered. Also,
Floating and scattered contents are not preferable because they pollute the environment.

The low molecular weight regenerated chitosan microparticles used in the aerosol agent have a coefficient of variation in the particle diameter distribution when dried in the range of 0.50 to 1.35, preferably 0.6 to 1.0.
Are preferred. The coefficient of variation referred to in the present invention is a value obtained by dividing the standard deviation of the particle diameter distribution by the average particle diameter. When the coefficient of variation is greater than 1.35, the mixture of particles having a large particle diameter results in a difference in the rate of moisture absorption / desorption of each individual particle. The wound surface becomes jerky, delays healing, and is unpleasant and undesirable. When the coefficient of variation is less than 0.50, the low molecular weight regenerated chitosan microparticles covering the wound surface are densely laminated and adhered, the voids between the particles are reduced, and the exudate in the body is absorbed and wetted. In order to prevent swelling at the time, a large amount of regenerated chitosan microparticles having a low molecular weight are required, which is not preferable.

[0013] The low molecular weight regenerated chitosan micro-colored granular material used in the present invention is obtained by stirring the low molecular weight regenerated chitosan obtained by the above method together with a coloring agent in water, and pulverizing, dispersing, and pulverizing with a homogenizer or the like. After the suspension is formed, the suspension is discharged and dried together with pressurized air in a high-temperature atmosphere.

Examples of the coloring agent include inorganic green pigments such as titanium oxide and cobalt titanate, inorganic blue pigments such as ultramarine and navy blue, titanium oxide coated mica, titanium oxide coated bismuth oxychloride, bismuth oxychloride, Metal powder pigments such as titanium coated talc, aluminum powder, and copper powder, Red No. 201, Red No. 202, Red No. 204, Red No. 205, Red No. 220
No. Red 226, Red 228, Red 405, Orange 204, Yellow 205, Yellow 401 and Blue 404
No. 3, organic pigment No. 3, red No. 104, red No. 106
No. 106, Red No. 227, Red No. 230, Red No. 401, Red No. 505, Orange No. 205, Yellow No. 4, Yellow No. 5, Yellow No. 202, Yellow No. 203, Green No. 3, and Blue No. 1 Organic pigments such as zirconium, barium or aluminum lakes, and natural pigments such as chlorophyll, β-carotene, catechin, shikonin, lignin, etc., among these, without adversely affecting the wound surface and being coated It is appropriately selected from those which can be sufficiently confirmed visually. The mixing ratio of the low molecular weight regenerated chitosan and the colorant is not particularly limited as long as the coloration can be confirmed.

The aerosol container is not particularly limited, and its material may be appropriately selected from plastic, glass, aluminum, iron and the like. As a valve to be used, a powder valve in which powder is unlikely to accumulate in a flow path or a seal portion of a stem gasket is preferable.

An aerosol for wound covering is prepared by a conventional method by dispersing a low molecular weight regenerated chitosan microparticle or a low molecular weight regenerated chitosan microcolored particle in a dispersion solution and a propellant liquefied under pressure by a conventional method. It is generally obtained by filling a container used as an aerosol container.

As the dispersion solution, alcohols such as ethanol, methanol and isopropyl alcohol are preferable, and the low molecular weight regenerated chitosan microparticles or the low molecular weight regenerated chitosan microcolored particles to be used can keep the particles in a dry state. is important. The weight ratio of the low molecular weight regenerated chitosan microparticles or the low molecular weight regenerated chitosan microcolored particulates to the dispersion solution is 1: 1.0, whereby a good dispersion state can be obtained.
The range of -2.0 is preferable.

A preservative or preservative may be added to the solution so as to withstand long-term storage. Examples of the type of preservative or preservative include parabens such as benzalkonium chloride, methyl paraoxybenzoate, ethyl paraoxybenzoate, propyl paraoxybenzoate, and butyl paraoxybenzoate, which are appropriately selected and used. Can be

The propellant to be used is not particularly limited, but hydrocarbons such as butane, propane and liquefied petroleum gas, ethers such as dimethyl ether, fluorocarbons such as fluorocarbon, chlorofluorocarbon and bromochlorofluorocarbon, and the like. Compressed gases such as a mixture, nitrogen, carbon dioxide, compressed air, nitrous oxide and the like can be mentioned, and these are appropriately selected and used.

The mixing ratio of the propellant and the low molecular weight regenerated chitosan microparticles or the low molecular weight regenerated chitosan microcolored particles is not particularly limited, and is preferably in the range of 2: 1 to 1000: 1 by weight. The internal pressure of the aerosol may be any pressure as long as the contents are generally used for powder formulations,
What is necessary is just to select suitably from the range of 0.1-1.0 MPa at 25 degreeC.

[0021]

EXAMPLES Hereinafter, the present invention will be described specifically with reference to examples, but the present invention is not limited to these ranges.
The methods of measuring the diameter expansion coefficient, the moisture absorption and absorption, the moisture release and the adhesion area by the spray pattern measured in the examples were measured by the following methods.

Measurement method of diameter expansion coefficient (1) Ultra-low molecular weight regenerated chitosan fine particles are ultrasonically dispersed in ethanol, and the dispersion is measured using a laser diffraction / scattering measurement apparatus (LS130, manufactured by Beckman Coulter, Inc.). The average particle diameter was measured in μm units, and this was taken as the unexpanded diameter. (2) The regenerated chitosan fine particles having a reduced molecular weight were ultrasonically dispersed in water, and the average particle diameter was measured in μm using the above-mentioned laser diffraction / scattering method measuring apparatus. (3) The diameter expansion coefficient was obtained by the following equation.

(Equation 1)

Method for Measuring Moisture Absorption and Moisture (1) About 0.5 g of regenerated chitosan microparticles in a dry state was placed in a weighing bottle of known weight, and left at 105 ° C. for 1 hour with the lid open. Thereafter, the mixture was placed in a desiccator containing silica gel, left standing at 25 ° C. for 1 hour, cooled, and weighed. From the difference in the weight of the weighing bottles, the weight of the low molecular weight regenerated chitosan fine granules was determined and defined as the dry weight. (2) Then, after opening the lid of the weighing bottle in a thermo-hygrostat adjusted to 37 ° C. and a relative humidity of 90%, and allowed to stand for 1 hour,
The lid was closed, the weighing bottle was taken out, and the weight was weighed. The weight of the low molecular weight regenerated chitosan microparticles was determined from the difference in the weight of the weighing bottles, and defined as the weight after moisture absorption. (3) The moisture absorption was determined by the following equation.

(Equation 2)

Measuring method of moisture release humidity (1) About 0.5 g of regenerated chitosan microparticles in a dry state were placed in a weighing bottle of known weight, and left at 105 ° C. for 1 hour with the lid open. Thereafter, the mixture was placed in a desiccator containing silica gel, left standing at 25 ° C. for 1 hour, cooled, and weighed. From the difference in the weight of the weighing bottles, the weight of the low molecular weight regenerated chitosan fine granules was determined and defined as the dry weight. (2) Then, after opening the lid of the weighing bottle in a thermo-hygrostat adjusted to 37 ° C. and a relative humidity of 90%, and allowed to stand for 1 hour,
The lid was closed, the weighing bottle was taken out, and the weight was weighed. The weight of the low molecular weight regenerated chitosan microparticles was determined from the difference in the weight of the weighing bottles, and defined as the weight after moisture absorption. (3) Then, the lid of the weighing bottle was opened and placed in a thermo-hygrostat adjusted to 37 ° C. and a relative humidity of 40%, and allowed to stand for 1 hour.
The lid was closed, the weighing bottle was taken out, and the weight was weighed. The weight of the low molecular weight regenerated chitosan microparticles was determined from the difference in the weight of the weighing bottles, and was defined as the weight after moisture release. (4) The moisture release humidity was determined by the following equation.

(Equation 3)

Method for Measuring Adhered Area by Spray Pattern (1) A 3% aqueous agar solution is prepared, and is 8 cm long and 8 cm wide.
m, and cast into a container having a depth of 2 mm, and allowed to stand at room temperature to solidify. (2) Set the coagulated agar plate vertically, and remove 1 plate from the agar plate.
The aerosol was fixed so that the injection port of the aerosol came at a position separated by 0 cm. (3) The aerosol was sprayed on the agar plate for 1 second. (4) The agar plate was returned to the original position, and a transparent graph paper having a scale of 1 mm was covered on the adhered substance, the adhered area was visually checked, and the area was measured.

Example 1 15 liters of hot water at 50 ° C.
g / l of sodium perborate was added and dissolved, the degree of deacetylation was 82%, and the average molecular weight was 230,000.
Of chitosan was added and reacted with stirring for 1 hour. After the reaction, this chitosan was taken out and sufficiently washed with water to obtain 650 g of low molecular weight chitosan having a degree of deacetylation of 82% and an average molecular weight of 35,000. 650 g of the obtained low molecular weight chitosan was dissolved in 9,350 g of water containing 325 g of acetic acid to obtain a low molecular weight chitosan acidic aqueous solution having a viscosity of 4,000 cP at 25 ° C. Then, the acidic aqueous solution of low molecular weight chitosan was added with 6% caustic soda, 20% methanol, 74%
% Aqueous solution of chitosan is dropped from a nozzle having a pore size of 0.25 mmφ by a predetermined amount into a basic aqueous solution composed of 0.2% water to coagulate and regenerate the low-molecular-weight acidic aqueous solution of chitosan into granular porous material. A chemically regenerated chitosan 101 was obtained.

Thereafter, 5 l of water was added thereto, and the mixture was stirred at 11,900 rpm for 1 minute using a homogenizer to obtain a milky suspension having a chitosan concentration of 4.3%. Next, the suspension was discharged and dried at a flow rate of 25 ml / min with a pressurized air of 3.0 kg / cm ² in a constant temperature atmosphere of 175 ° C., and then collected by a cyclone collector to obtain a low molecular weight regenerated chitosan. 600 g of fine granular material was obtained. Then, the low molecular weight regenerated chitosan microparticles were classified using an air classifier (Spedick 250, manufactured by Seishin Enterprise Co., Ltd.). Then, using the low molecular weight regenerated chitosan fine granules, the supply rate was 1.5 kg / hour, the number of rotations of the classifier was adjusted to the value shown in Table 1, and the classified dry state of Samples 1 to 11 was reduced. As a result, 11 kinds of molecular regenerated chitosan fine particles were obtained.

Using the obtained samples 1 to 11, the average particle diameter, which is the geometric mean of the equivalent sphere diameter, the variation coefficient of the particle diameter distribution, and the diameter expansion coefficient were measured. The results are shown in Table 1.

[0029]

[Table 1]

As is apparent from Table 1, the diameter expansion coefficient increased as the average particle diameter increased, and gradually decreased while the peak of the average particle diameter of Sample 4 varied around 5.2 μm. 0.5 g of each of the obtained Samples 1 to 11 was collected and dispersed in 0.8 g of an ethanol solution containing 1,000 ppm of benzalkonium chloride, and then placed in a metal and pressure-resistant aerosol container. .5 g was added and charged by a conventional method so as to become 0.28 MPa at 25 ° C.,
Aerosols 1 'to 11' were obtained.

The contents were sprayed into the weighing bottles using the respective aerosols, and the contents were adhered to the weighing bottles. After that, LPG in the contents was evaporated, and the moisture absorption and release of moisture was measured using a weighing bottle to which only the low molecular weight regenerated chitosan microparticles had adhered. The results are shown in Table 2.

Then, after shaving the back hair of one adult hybrid dog weighing 20.5 kg, a vertical scalpel was used with a surgical scalpel.
A single cross cut of m, width 1 cm, depth 1 mm was made, and aerosol 2 ′ was sprayed onto the bleeding site from a distance of 10 cm for 2 seconds, and the time until hemostasis was measured. The results are shown in Table 2. In the same manner, the time until hemostasis was measured using the aerosol agents 1 ', 3' to 11 ', and the results are shown in Table 2.

[0033]

[Table 2]

As is clear from Table 2, the moisture absorption and release characteristics gradually increase as the average particle size increases.
Of the aerosol 4 ′ having an average particle diameter of 5.2 μm gradually decreased to a peak. The aerosol preparations 2 'to 9' in which the average particle diameter of Samples 2 to 9 was in the range of 1.0 to 10.9 were preferable because the hemostatic time was 8 minutes or less. In particular, the aerosols 10 'and 11' significantly reduced the moisture absorption and release of moisture as compared with the aerosols 3 'to 8', and the hemostasis time was prolonged accordingly. The aerosol 1 'scattered in the air due to the small average particle diameter of the regenerated chitosan microparticles having a reduced molecular weight when injected, and could not cover the wound surface, so that the hemostatic time could not be measured. Was.

Example 2 The same operation as in Example 1 was performed to obtain 600 g of regenerated chitosan fine particles having a reduced molecular weight.
Thereafter, the low molecular weight regenerated chitosan fine granules are subjected to an air classifier (Sedic Corporation, Spedick 250).
And classified. Next, the supply amount of the low molecular weight regenerated chitosan microparticles was adjusted to 1.5 kg / hour, the classifier rotation speed was adjusted to 2,400 rpm, and the dried low molecular weight regenerated chitosan microparticles of Samples 12 to 17 were dried. Six types were obtained.

Using each of the obtained samples 12 to 17, similarly, for each of the low-molecular-weight regenerated fine chitosan microparticles, measurement of the average particle diameter, which is the geometric average of the equivalent sphere diameter, the variation coefficient of the particle diameter distribution, and the diameter expansion coefficient And the results are shown in Table 3.

[0037]

[Table 3]

As is clear from Table 3, the average molecular diameter of the regenerated chitosan fine particles having a low molecular weight is 10.2 to 10.8.
In the range, the diameter expansion coefficient gradually increased as the variation coefficient of the particle diameter distribution increased, and gradually decreased to a peak near the variation coefficient of 1.00.

0.5 g of each of the obtained samples 12 to 17 was collected and dispersed in 0.8 g of an ethanol solution containing 1,00 ppm of benzalkonium chloride, and then placed in a metal pressure-resistant aerosol container. , LPG49.5g
Was added thereto at 25 ° C., and the mixture was filled by a conventional method so that the pressure became 0.28 MPa, thereby obtaining aerosols 12 ′ to 17 ′.

Using each aerosol, the contents were sprayed into a weighing bottle, and the contents were adhered to the weighing bottle. After that, LPG in the contents was evaporated, and the moisture absorption and desorption were measured using a weighing bottle to which only the low molecular weight regenerated chitosan microparticles had adhered. The results are shown in Table 4.

Next, the performance of the above aerosol was evaluated by the following method. After shaving the back hair of one adult mongrel dog weighing 15.3 kg, length 1c with a surgical scalpel
One cross cut of m, 1 cm in width, and 1 mm in depth was made, and an aerosol 12 'was sprayed onto the bleeding site from a distance of 10 cm for 2 seconds, and the time until hemostasis was measured. The results are shown in Table 4. In the same manner, the time until hemostasis was measured using the aerosol agents 13 'to 17', and the results are shown in Table 4.

[0042]

[Table 4]

As is clear from Tables 3 and 4, Sample 13 in which the coefficient of variation of the particle diameter distribution was 0.50 to 1.35.
The aerosol agents 13 'to 16' using Nos. To 16 have high moisture absorption and release of moisture for each particle, that is, they can quickly absorb and release moisture, so that the hemostatic time can be shortened accordingly. . The aerosol agent 12 'using the sample 12 having a coefficient of variation of 0.3 had a small water absorption and release of moisture for each particle, so that the hemostatic time was also long. In addition, the aerosol 17 ′ using the sample 17 having a coefficient of variation of 1.40 showed a large difference in the size of each particle, so that the moisture absorption and release were small, and the hemostatic time was long.

Example 3 After adding and dissolving sodium perborate in the amounts shown in Table 5 in 10 l of 50 ° C. hot water, the degree of deacetylation was 82% and the average molecular weight was 230,000.
Of chitosan was added, and the mixture was reacted with stirring for a time corresponding to the conditions described in Table 5. After the reaction, each chitosan was taken out, washed sufficiently with water, and measured. The degree of deacetylation was 82%, and the average molecular weight was 7,000 to 226,0.
Thus, five kinds of low molecular weight chitosan No. 00 were obtained. Each of the obtained low-molecular-weight chitosans was dissolved in acetic acid in the same manner as in Example 1, coagulated and regenerated in a basic aqueous solution, washed sufficiently with water, and then made into a milky suspension with a homogenizer. After being discharged and dried in the atmosphere, it is classified using a wind classifier (Sedic Corporation, Spedick 250).
A regenerated chitosan microparticle having a low molecular weight was obtained. Next, the supply amount of each of the low molecular weight regenerated chitosan microparticles was 1.5 k.
g / hour, the number of revolutions of the classifier was adjusted to 3,200 rpm, and samples 18 to 22 of five kinds of classified dry low molecular weight regenerated chitosan fine granules having an average diameter of 5.0 μm were obtained.

Using the obtained samples 18 to 22, the average particle diameter, which is the geometric mean of the sphere equivalent diameter, the variation coefficient of the particle diameter distribution, and the diameter expansion coefficient were measured, and the results are shown in Table 5.

[0046]

[Table 5]

As is clear from Table 5, as the average molecular weight of the regenerated low molecular weight chitosan microparticles increases,
The diameter expansion coefficient gradually increased, and the average molecular weight of Sample 20 was 80,000.
, And gradually decreased thereafter. In sample 18, the diameter expansion coefficient could not be measured because the particles of the regenerated chitosan microparticles in water were extremely expanded and partially dissolved in water.

0.5 g of each of the obtained Samples 18 to 22 was collected, and 1,000 ppm of benzalkonium chloride was used.
Is dispersed in 0.8 g of an ethanol solution containing, and then placed in a metal pressure-resistant aerosol container.
9.5 g was added, and the mixture was charged by a conventional method so that the pressure became 0.28 MPa at 25 ° C., to obtain aerosols 18 ′ to 22 ′.

The contents were sprayed into the weighing bottles using the respective aerosols, and the contents were adhered to the weighing bottles. Then, LPG in the contents was evaporated, and the moisture absorption and desorption were measured using a weighing bottle to which only the low molecular weight regenerated chitosan microparticles had adhered. The results are shown in Table 6.

Then, after shaving the back hair of one adult mongrel dog weighing 16.5 kg, a vertical scalpel was used with a surgical knife.
One cross cut of m, width 1 cm and depth 1 mm was made, and an aerosol 19 ′ was sprayed on the bleeding site from a distance of 10 cm for 2 seconds, and the time until hemostasis was measured. The results are shown in Table 6. The time until hemostasis was measured using the aerosols 18 ', 20' to 12 'in the same manner, and the results are shown in Table 6.

[0051]

[Table 6]

As apparent from Tables 5 and 6, Sample 1 having an average molecular weight in the range of 10,000 to 200,000 was used.
The average molecular weight of sample 22 was 226, and the moisture absorption and release of aerosol agents 19 'to 22' using 9 to 21 were as follows.
A value higher than a value of 000 was good, and a shorter hemostasis time was preferred accordingly. On the other hand, when the aerosol 18 'was sprayed, the low molecular weight regenerated chitosan microparticles of the content adhered to the wound surface, but were extremely swollen by the exudate in the body,
The dissolution resulted in insufficient wound surface coverage.

Example 4 The same operation as in Example 1 was performed to obtain 10 l of granular porous low molecular weight regenerated chitosan. To this, 5 l of water containing 2 g of Food Color Yellow No. 4 (manufactured by Daiwa Kasei Co., Ltd.) was added, and 11,900 rpm was added using a homogenizer.
After stirring for 1 minute at m, a colored suspension having a chitosan concentration of 4.3% was obtained.

The suspension was supplied at a flow rate of 25 m / min to 3.0 k
The mixture was discharged and dried in a high-temperature atmosphere at 175 ° C. together with g / cm ² of pressurized air, and collected by a cyclone collector to obtain 600 g of regenerated chitosan micro-colored granules having a reduced molecular weight.

The low molecular weight regenerated chitosan micro-colored granular material was classified using an air classifier (Spedick 250, manufactured by Seishin Enterprise Co., Ltd.). The supply amount of the low molecular weight regenerated chitosan micro-colored granules was 1.5 kg / hour, and the rotation speed of the classifier was adjusted to 3,200 rpm to obtain the dry low molecular weight regenerated chitosan micro-colored granules of Sample 23. Was.

The average particle diameter, which is the geometric mean of the equivalent spherical diameters, the variation coefficient of the particle diameter distribution, and the diameter expansion coefficient of the obtained dried low molecular weight regenerated chitosan micro-colored granular material were measured. The results are shown in Table 7. For reference, Example 1
The result of Sample 4 was also added.

Next, 0.5 g of the obtained sample 23 was sampled, dispersed in 0.8 g of an ethanol solution containing 1,000 ppm of benzalkonium chloride, and then placed in a metal pressure-resistant aerosol container. Then, 0.5 g was added, and the mixture was charged by a conventional method so that the pressure became 0.28 MPa at 25 ° C., to obtain an aerosol 23 ′.

The contents were sprayed into the weighing bottle using the aerosol agent 23 ', and the contents were adhered to the weighing bottle. Thereafter, LPG in the contents was evaporated, and moisture absorption and release were measured using a weighing bottle to which only the low molecular weight regenerated chitosan micro-colored granules adhered. The results are shown in Table 8.
For reference, the results of the aerosol 4 'of Example 1 are also shown.

Next, the back hair of one adult hybrid dog weighing 6.0 kg was shaved, and then 1 cm long, with a surgical scalpel.
One cross cut with a width of 1 cm and a depth of 1 mm was made, and an aerosol 23 'was sprayed onto the bleeding site from a distance of 10 cm for 2 seconds, and the time until hemostasis was measured.
Table 8 shows the results. For reference, the results of the aerosol 4 'of Example 1 are also shown. Next, the aerosol agent 23 'was measured by a method for measuring the adhered area by a spray pattern, and the results are shown in Table 8. For reference, the results of the aerosol 4 'of Example 1 are also shown.

[0060]

[Table 7]

[0061]

[Table 8]

As is clear from Tables 7 and 8, the aerosols 4 'and 23' have an average particle diameter, a coefficient of variation of the particle diameter distribution, a diameter expansion coefficient, a moisture absorption / humidity, a moisture release humidity, and a hemostatic time. Aerosol 23 'which is the same aerosol but is filled with regenerated low molecular weight chitosan micro-colored granules
Since colored low molecular weight regenerated chitosan microparticles were used, the sprayed portion was clear, and the attached portion was more clearly recognized than the uncolored aerosol agent 4 '. Therefore, it is suitable for visually confirming the attached range.

Comparative Example 1 15 l of water was added to 1,000 g of chitosan having a degree of deacetylation of 82%, an average molecular weight of 35,000 and an average particle diameter of 300 μm, and the mixture was stirred at 11,000 rpm for 10 minutes using a homogenizer. A suspension of finely crushed material was obtained.

This suspension was subjected to a flow of 3.0 k at a flow rate of 25 m / min.
The dried product was discharged into a high-temperature atmosphere of 175 ° C. together with pressurized air of g / cm ² , and the dried product was collected by a cyclone collector to obtain 800 g of fine chitosan particles.

The fine chitosan particles were classified using an air classifier (Spedick 250, manufactured by Seishin Enterprise Co., Ltd.). Thereafter, the supply amount of the chitosan fine granules divided into four was set to 1.5 kg / hour, and the number of rotations of the classifier was adjusted to the value shown in Table 9 to adjust the sample 24 of the dry chitosan fine granules.
~ 27. The average particle diameter, which is the geometric mean of the equivalent sphere diameters of the obtained chitosan microparticles, the variation coefficient of the particle diameter distribution, and the coefficient of diameter expansion were measured. The results are shown in Table 9.

[0066]

[Table 9]

As is clear from Table 9, Samples 24-27
Has a diameter expansion of 113 to 124%,
9, which is not preferable because the value is lower than the diameter expansion coefficient of 130 to 138%.

Next, 0.5 g of each of the obtained Samples 24 to 27 was collected, and each of Benzalkonium chloride 1,00
After dispersing in 0.8 g of an ethanol solution containing 0 ppm, the mixture is placed in a metal pressure-resistant aerosol container.
49.5 g of PG was added, and the mixture was charged by a conventional method so as to have a pressure of 0.28 MPa at 25 ° C., thereby obtaining aerosols 24 ′ to 27 ′.

The contents were sprayed into the weighing bottles using the aerosols 24 'to 27', and the contents were adhered to the weighing bottles. After that, LPG in the contents was evaporated, and the moisture absorption and release were measured using a weighing bottle to which only the chitosan microparticles had adhered. The results are shown in Table 10.

Then, after shaving the back hair of one adult mongrel dog weighing 16.1 kg, a vertical scalpel was used with a surgical scalpel.
One cross cut of m, 1 cm in width and 1 mm in depth was made, and an aerosol 24 'was sprayed on the bleeding site from a distance of 10 cm for 2 seconds, and the time until hemostasis was measured. The results are shown in Table 10. In the same manner, the time until hemostasis was measured using the aerosols 25 'to 27', and the results are shown in Table 10.

[0071]

[Table 10]

The moisture absorption of the aerosols 24 'to 27' is 17.1 to 17.8%, and the aerosols 6 'of Example 1 are used.
Unfavorably, the value is low as compared with the moisture absorption of 20.2 to 20.9%. Also, aerosol agents 24 'to 27
The moisture release of 6 ′ to 62.8% was 61.5 to 62.8%, and the moisture absorption of the aerosols 6 ′ to 9 ′ of Example 1 was 65.0 to 66.8.
%, Which is not preferable because the value is low. The hemostatic time was also much longer at 10 minutes for the aerosols 24 'to 27', compared to 7 to 8 minutes for the aerosols 6 'to 9' of Example 1.

The fine particulate chitosan used as an aerosol has a smaller moisture absorption and moisture release compared to the low molecular weight regenerated chitosan fine particulate, so that the hemostatic time is longer and it is difficult to use it as an aerosol. It is clear that this is not preferred.

[0074]

The aerosol according to the present invention is an aerosol using low molecular weight regenerated chitosan microparticles or low molecular weight regenerated chitosan microcolored particles having high moisture absorption and release, and thus has a high hemostasis time. Has a hemostatic effect, anti-inflammatory effect, wound healing effect, cut wound, abrasion wound,
When an aerosol is sprayed and adhered to the external wound such as exfoliated wounds and cut wounds, or the wounds such as surgery, the wound surface is covered with a small amount of adhesion and has an excellent covering effect. The use of a fine, low molecular weight regenerated chitosan fine particle which is good without jigging and has a low molecular weight is advantageous in that the range of application can be clearly confirmed visually and an arbitrary amount of adhesion can be attached.

 ──────────────────────────────────────────────────続 き Continued on the front page (72) Inventor Yoshihide Kawamura 89-5 Oyama, Koyama-cho, Sunto-gun, Shizuoka Prefecture (72) Inventor Shigehide Kusaka 142-3, Fujimagari, Koyama-cho, Sunto-gun, Shizuoka Prefecture (72) Inventor Hiroaki Tanibe Shizuoka 1959-37 Higashi-Tanaka, Gotemba-shi, F F term (reference) 4C076 AA24 BB31 CC19 DD19 DD34 DD37 4C086 AA01 EA23 MA03 MA05 MA13 NA05 ZA89

Claims (2)

[Claims] An average molecular weight of 10,000 to 200,0.
The regenerated chitosan having a molecular weight of 00 is sprayed with a dispersion solution of a fine granular material having an average particle diameter of 1.0 to 11.0 μm when dried and a coefficient of variation of the particle diameter distribution of 0.50 to 1.35. An aerosol for covering a wound surface, which is filled in a container together with the agent. 2. The aerosol composition for covering a wound surface according to claim 1, wherein the fine granular material of the regenerated low molecular weight chitosan is colored with a coloring agent.