JPH10279606A - Nasal and oral anti-inflammatory spray - Google Patents

Abstract

PROBLEM TO BE SOLVED: To obtain a nasal and oral spray which, when administered to the nasal mucosa or the oral mucosa, can exhibit excellent effect of alleviating various inflammation symptoms such as pollinosis and stomatitis by using chitin as the active ingredient. SOLUTION: The chitin herein mentioned means poly-N-acetyl-D-glucosamine obtained from the exoskeletons of Crustacea and of beetles and the calcified internal shells of cuttlefishes and derivatives thereof. The derivatives include deacetylated chitin and chitosan. The chitin has a degree of deacetylation of desirably 20% or below, more desirably 5% or below. Examples of the forms of the chitin used in the nasal and oral spray include powders, granules and short fibers, and especially a powder having a particle size distribution having an effective particle diameter of 20-250 μm is desired, because it can deposit on the nasal mucosa in a high proportion when administered through the nostril. The chitin powder may be a commercially one or a powder prepared by dissolving a molding in a solvent, forming the solution into a desired molding and grinding this molding. Especially, a chitin powder obtained from a molding, such as a sponge or granules, made from the powder containing the solvent is desirable.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a nasal and oral anti-inflammatory spray, and more particularly, it is administered to the nasal mucosa and the oral mucosa to prevent various inflammatory symptoms in the nasal cavity and oral cavity such as hay fever and stomatitis. The present invention relates to a nasal and oral anti-inflammatory spraying agent having an effective anti-inflammatory action.

[0002]

2. Description of the Related Art Conventionally, ointments, jellies, nasal solutions and sprays have been known as preparations intended for nasal and buccal administration. However, it is difficult to apply an ointment or jelly to a deep part of the nasal cavity such as the upper turbinate, and it is difficult to sufficiently exert the effect. In addition, nasal drops and conventional sprays have difficulty in keeping the active medicine contained therein in the nasal cavity for a long time. As an anti-inflammatory agent administered to the nasal cavity and the oral cavity region, for example, a beclomethasone propionate preparation (trade name: Rinocoat, manufactured by Teijin Limited) is known for nasal use. However, these drugs cannot be used commonly for the nasal cavity and the oral cavity, and different drugs must be used for each administration site, which is inconvenient to use properly. In addition, since the medicinal ingredient is a steroid, and care must be taken during handling, it is not safe to use, and improvements are required. On the other hand, a method in which a powder of chitin or a derivative thereof is applied to the nasal mucosa and used is described in JP-T-7-507303.
However, in this publication, chitin only plays a role as a carrier for pharmaceuticals, and at least 10% of the carrier is a nonionic cellulose ether derivative, and chitin alone shows good adhesion to the nasal mucosa, It does not prevent inflammation and, therefore, does not mean that chitin alone can achieve the same effect without the inclusion of other drugs. JP-A-58-135805 describes a drug-free powdery nasal mucosal coating protective agent that is effective for treating and preventing allergic rhinitis. However, the above-mentioned protective agent, when administered to the nasal mucosa that is sensitive to odors and irritation, forms a fluid that has substantially no odor and irritation and absorbs water on the nasal mucosa and gradually flows over the nasal mucosa. The effect of the invention is only described as having a certain effect by covering and protecting the intranasal mucosa. Furthermore, the effects described in the embodiments are not exceptional.

[0003]

SUMMARY OF THE INVENTION An object of the present invention is not only to protect the mucous membrane in the nasal cavity and throat, but also to provide an anti-inflammation for the nasal and oral cavities which has an excellent inhibitory and therapeutic effect on various inflammations on the mucous membrane. It is to provide a dusting agent.

[0004]

Means for Solving the Problems The present inventors have conducted intensive studies to solve the above-mentioned problems, and as a result, it has been found that an anti-inflammatory spray for nasal and oral cavities comprising chitin is effective against various inflammatory symptoms in the nasal cavity and the oral cavity. It has been found to be effective and has reached the present invention. That is, the present invention provides a nasal and oral cavity anti-inflammatory spray containing chitin as an active ingredient.

[0005]

BEST MODE FOR CARRYING OUT THE INVENTION Hereinafter, the present invention will be described in detail.
Chitin in the present invention refers to poly-N obtained by treating exoskeletons such as crustaceans and beetles, and squid soft shells with hydrochloric acid and caustic soda, and decalcifying and deproteinizing.
-Acetyl-D-glucosamine or a derivative thereof.
As the derivative, deacetylated chitin or chitosan, further, poly-N-acetyl-D-glucosamine, an amino group of a glucosamine residue of deacetylated chitin, -OH group,
Alternatively, those in which a —CH ₂ OH group is modified by etherification, esterification, carboxymethylation, hydroxyethylation, O-ethylation and the like are also included.

It is well known that chitin has an anti-inflammatory effect, and the present inventors have already developed a wound covering protective material (trade name: Vesquitin W, manufactured by Unitika Ltd.) obtained by processing chitin into a nonwoven fabric. It is widely used for treating skin wounds such as burns and skin wounds. In the case report of Vesquitin W, the characteristics include relief of pain, good adhesion, good epidermis formation, formation of good granulation, and the like. It has been reported that in W-coated wounds, soothing of inflammation is observed due to the anti-inflammatory effect of chitin (New Drug and Clinical Laboratory, Vol. 41, No. 8, 1991, etc.).

[0007] The preferred degree of deacetylation of chitin in the present invention is 20% or less, more preferably 10% or less, and most preferably 5% or less. When the acetyl group of chitin is partially eliminated or is chitosanized, the degree of deacetylation can be reduced by acetylating the amino group of chitin. Acetylation is carried out, for example, by dissolving 60 g of caustic soda in methanol 1
It can be carried out by adding 1 kg of chitin and 1 kg of acetic anhydride to 1.25 L and reacting at 60 ° C. for about 2 hours. The acetylated chitin is dispersed in water, neutralized and filtered with diluted caustic soda, washed with tap water and ion-exchanged water, and sufficiently dehydrated under pressure.
Air dry. This reaction can be carried out in an appropriate step before or after the production of molded articles of various shapes described later.

Here, the degree of deacetylation refers to a value measured by the following method. Approximately 2g of sample is
Pour into 200 ml and stir at room temperature for 30 minutes. Next, the mixture was filtered through a glass filter to remove the aqueous hydrochloric acid solution.
And stirred for 30 minutes, filtered through a glass filter, poured into 200 ml of fresh methanol, and stirred for 30 minutes. After repeating this washing operation with methanol four times, air drying and vacuum drying are performed. After drying, about
0.2 g is precisely weighed, placed in a 100 ml Erlenmeyer flask, added with 40 ml of ion-exchanged water, and stirred for 30 minutes. Next, this solution is neutralized and titrated with a 0.1N aqueous solution of sodium hydroxide using phenolphthalein as an indicator. The degree of deacetylation (A) is determined by the following equation.

A (%) = [(2.03 × f × b × 10 ^-2 ) /
(A + 0.055 × f × b × 10 ^-2 )] × 100

Where a is the weight (g) of the sample, f is 0.1 N
-Potency of aqueous sodium hydroxide solution, b is the titer (ml) of 0.1N aqueous sodium hydroxide solution.

The chitin used in the anti-inflammatory spray for nasal and oral cavity of the present invention may be in any form as long as it can be used as a spray, such as powder, granules and short fibers. Among them, powdery ones are preferred from the viewpoint of dispersibility in the nasal and oral cavities and adhesion to the nasal and oral mucosa. Also, the effective particle size of the powder is 20-250μm
Those having a viscosity distribution of, for example, when administered into the nasal cavity through the nostrils, adhere to the nasal mucosa at a high rate, especially adherence to the inferior turbinate, nasal septum and inferior nasal passage,
Particularly preferred.

About 10 particles having an effective particle diameter of less than about 20 μm
If the amount occupies more than 20% by weight, more may reach the lungs or dissipate outside the nostrils when sprayed, while particles having an effective particle size of more than about 250 μm may be more than about 10% by weight. In a large amount, even if it adheres to the nasal mucosa, it may be easy to separate from the mucous membrane when absorbing water from the mucous membrane. The anti-inflammatory spray for nasal and oral cavities of the present invention has an effective particle size of about 90 to about 1% by weight.
Those between 50 μm are particularly preferred.

The chitin powder used in the present invention may be a commercially available one or a molded one. In the case of molding, chitin may be directly molded into a powder, or may be molded once into a chitin molded body having another shape, and then the chitin molded body may be powdered. When powder is obtained from a chitin molded body of another shape, the shape of the chitin molded body as a raw material may be any shape such as fibers, fibrils, sponges, granules and the like. In order to form a powder from these compacts, chitin is dissolved in a solvent to form a dope, and once the desired compact is formed, the compact may be ground. By taking such a process,
A fine and porous molded article can be produced. This is because chitin is formed into fibers, fibrils, sponges, granules, and the like while containing the solvent, and micropores generated when the solvent flows out by the coagulation liquid remain in the formed body. The chitin powder produced by the above method has extremely good absorption of water and the like.

Hereinafter, a method of forming a chitin molded body for each shape will be described. The chitin fiber can be formed, for example, by dissolving chitin in a solvent to form a dope, spinning the dope, and removing the solvent with a coagulating liquid. When the degree of deacetylation of chitin or a chitin derivative is low, a mixed solution of trichloroacetic acid and a halogenated hydrocarbon or a mixed solution of dimethylacetamide or N-methylpyrrolidone and lithium chloride is used as a solvent for preparing the dope. When chitin or a chitin derivative has a high degree of deacetylation, an aqueous solution of a dilute acid such as acetic acid is used. In order to form chitin fibers from the dope, for example, the dope is filtered through a stainless steel net to remove undissolved components and foreign substances, then transported and measured with a gear pump, etc., and water, methanol, propanol, and butanol are supplied from required nozzles. May be extruded and coagulated into a coagulating liquid composed of alcohols such as ketones and ketones such as acetone. The coagulated yarn is taken up, for example, at a speed of about 2 to 50 m / min with a rotating roller or the like, wound up with a winder or the like, further washed to remove the solvent contained in the yarn sufficiently, and dried. Good. A powder can be formed by crushing the obtained fiber with a crusher or the like.

In order to form chitin fibrils, a chitin solution and water may be stirred and mixed at a high speed, followed by coagulation and washing.
At this time, the higher the temperature of the water acting as the coagulating liquid, the larger the fibrils can be produced, and the lower the temperature, the longer the coagulation time, and it is possible to form fibrils of small size and uniform size. When mixing, for example, Nippon Seiki multi-blender mill BL
A type 4 or the like may be used. Further, the mixing speed is preferably 300 rpm or more. The mixing ratio of chitin solution to water is 0.5 to 2, more preferably 1 to 1.5, relative to 1 chitin solution.
Washing can be performed by combining one or more of filtration or centrifugation, warm water or boiling. A powder can be formed by crushing the obtained fibrils with a crusher or the like.

To form a chitin sponge, a chitin dope is mixed with a water-soluble polymer, preferably in powder form,
After dispersing and solidifying the water-soluble polymer in chitin dope,
Molding can be performed by removing the water-soluble polymer from the obtained molded body. A water-soluble polymer is a solid at room temperature,
It refers to a natural polymer or a synthetic polymer soluble in water. In the present invention, for example, polyvinyl alcohol and agar are preferably used. As the polyvinyl alcohol, those having a degree of saponification of 60 mol% or more, which can be dissolved in low-temperature or high-temperature water, and those having a degree of polymerization of 50 to 20,000 are preferably used. Those which are soluble and have a degree of saponification of 95 mol% or more are preferably used. Agar refers to a viscous substance present as a cell membrane component in red algae such as Tengusa or a substance obtained by freeze-drying the substance, and agarose, agaropectin and derivatives thereof separated therefrom. As polypropylene glycol or polyethylene glycol, those having a molecular weight of 1,000 or more are preferably used. The mixing ratio of chitin dope and water-soluble polymer is chitin dope / water-soluble polymer = 1/5 by weight ratio.
The range of ５5/1 is preferred. As a chitin dope coagulating liquid containing a water-soluble polymer, a liquid similar to that used for forming chitin fibers can be used. The chitin sponge obtained as described above may be washed, sufficiently removed of the solvent contained in the sponge, and then dried. A powder can be formed by crushing the obtained sponge with a crusher or the like.

The chitin granules can be formed by dropping a chitin dope into a coagulation bath and coagulating it. As used herein, the term "granules" refers to shapes such as spheres, rice grains, cylinders, flat spheres, and other irregular shapes. The term “dropping” means that the chitin dope is extruded from the tip of a nozzle or a tube or the like and drops drop by drop into the coagulation bath discontinuously. As the coagulating liquid for chitin dope, the same liquid as that used for forming chitin fibers can be used. The size of the granules is determined by the size of the droplet of the dope. That is,
The size of granules to be formed can be controlled by the diameter of the nozzle for discharging the dope and the viscosity of the dope. The chitin granules obtained as above may be washed, the solvent contained in the granules may be sufficiently removed, and then dried. A powder can be formed by crushing the obtained granules with a crusher or the like.

The powder obtained as described above has a property that, in the step of coagulating the dope in a coagulation bath, micropores formed when the solvent is eliminated from each compact remain, and chitin is hydrophilic. When combined with the nasal and oral mucosa, it is easy to absorb water on the mucous membrane and can adhere quickly and firmly. Is superior to that of Comparative Example 1 in terms of adhesiveness. As a result, it is particularly preferable because, in addition to suppressing the inflammatory reaction due to the anti-inflammatory effect of chitin, the contact of the antigen with the mucous membrane can be inhibited.

The anti-inflammatory spray for nasal and oral cavities of the present invention may contain, if necessary, known lubricants, binders and diluents in addition to chitin in order to improve the physical properties, appearance and smell of the preparation. , A coloring agent, a flavoring agent, a preservative, a surfactant and the like. Examples of the lubricant include talc, stearic acid and salts thereof, and waxes. Examples of the binder include starch, dextrin, tragacanth, gelatin, polyvinylpyrrolidone, polyvinyl alcohol and the like. As a diluent,
For example, starch, crystalline cellulose, dextrin, whey, mannitol, sorbitol, anhydrous calcium phosphate and the like can be mentioned. Examples of the flavoring agent include menthol, citrus flavor and the like. They can usually be included up to a maximum of about 10% by weight per total weight.

The method of administering the anti-inflammatory spray for nasal cavity of the present invention includes various methods. For example, there is a known method in which a container such as a capsule (hard capsule made of gelatin) described in the Japanese Pharmacopoeia is filled with a spraying agent, and the spraying agent in the capsule is sprayed into a nasal cavity by a sprayer.
In this method, for example, 40 mg of chitin powder is filled into capsules (size: capsule number 3, base: gelatin) described in the Japanese Pharmacopoeia, and the capsules are sprayed for nasal use (trade name: Publyzer, Inc.). Ishikawa Seisakusho). A nasal sprayer consists of a spraying tool with a rubber ball for delivering air and a nozzle for spraying the spray, and a cap with a needle for piercing the capsule. After setting the above capsule in a spray tool,
By placing a cap with a needle (diameter 0.8 mm), the needle can penetrate the capsule and make holes at both ends of the capsule. By removing the cap, inserting the tip of the nasal sprayer into the nasal cavity, and then pushing the rubber ball to send air, the chitin powder can be ejected from the nozzle tip of the spray tool. When administered by the above-mentioned method, scattering to the outside is small, and it can be reliably and uniformly administered to the site of intranasal inflammation.

The spray of the present invention can be dispersed in a liquid and administered as a nasal solution or a spray, or enclosed in a spray tube together with a gas and administered as a spray. When dispersed in a liquid, for example, it may be dispersed in water, ethyl alcohol, or the like. Also, when enclosed in a spray can with gas, as a propellant, for example, air,
Carbon dioxide or the like may be used. When administered in the form of a dispersion in a liquid, unlike the conventional nasal solution, the active ingredient is not dissolved in the liquid, so that it is difficult to administer an excessive amount. In addition, since the spraying agent is present in a state in which it is easily adhered to the mucous membrane, it can be adhered to the mucous membrane of the nasal cavity for a long time, and the effect can be maintained for a long time.

The anti-inflammatory spray for nasal and oral cavities of the present invention comprises hay fever,
It can be used for sites of inflammation associated with diseases in the rhinology, throat, and oral surgery fields such as allergic rhinitis and stomatitis.
When the nasal and oral cavity anti-inflammatory spraying agent of the present invention is applied to the above-mentioned inflamed site, the induction of mucous membrane is effectively performed by the synergistic effect of the anti-inflammatory action of chitin and the coating of mucous membrane with chitin in powder form. In addition, the thickly formed mucous membrane creates a favorable environment for the cure of inflammation, and cures inflammation.

Further, the anti-inflammatory spray for nasal and oral cavity of the present invention comprises:
It can also be used to prevent the development of allergic symptoms sensitized nasally. For example, hay fever is a disease caused by the production of antibodies in the human body sensitized by pollen, and when pollen is inhaled again, the antibodies are rapidly and in large quantities produced, resulting in an inflammatory reaction. It is. The main symptoms are sneezing, runny nose, and itchy eyes. It is said that this sensitization is established from birth to school age.
During this period, the drug is used to coat the nasal mucosa during the pollen dispersal period, preventing pollen from adhering to the nasal cavity and reducing pollen sensitization, thereby reducing the possibility of future hay fever. Can be done.

In the present invention, chitin is applied to the mucous membrane. A sponge made of chitin (trade name: Vesquitin F, manufactured by Unitika Ltd.), which is already on the market, can be used for mucosal defects such as after intranasal surgery. On the other hand, it is used by filling and applying for the purpose of hemostasis and promotion of healing. Chitin is biodegradable, and is constantly degraded and renewed from the surface at the contact surface with the mucous membrane, and does not adhere to the mucous membrane.
The patient has little pain when removing the sponge made of chitin, and has been used with high evaluation. In general, chitin, which is a kind of saccharide, is considered to have low antigenicity as compared with proteins and the like, and in fact, as described below,
It has been confirmed by an intradermal reaction test using animals that there is almost no irritation to the living body. These facts suggest the safety of chitin when applied to mucous membranes.

[0025]

EXAMPLES The present invention will be described more specifically with reference to the following examples.

Example 1 Chitin powder (manufactured by Sanei Kogyo Co., Ltd.) was dissolved in a solvent composed of dimethylacetamide and lithium chloride to obtain a solution having a chitin concentration of 8% by weight. The resulting solution is filtered through a 1400 mesh stainless steel net, left in a defoamer, put in a tank, transported under pressure by a gear pump, and discharged from a 1000-hole nozzle (0.04 mm in diameter) into 70 ° C hot water. And wet spinning was performed. The obtained yarn was washed with water and dried to obtain a fiber having a density of 0.8 single yarn. The obtained fiber was washed, dried, cut into pieces having a length of 5 mm, and then pulverized by a ball mill to obtain chitin powder. The obtained chitin powder was classified with a mesh to obtain a powdery anti-inflammatory spray for nasal and oral cavities having a diameter of 45 to 120 μm. The degree of deacetylation of this chitin powder was 4%.

The above-mentioned chitin powder was immersed in a liquid obtained by dissolving 0.05 g of an edible blue pigment (edible blue No. 1) in 100 ml of ethanol and dried repeatedly to color the chitin powder. The colored powder was washed with ethanol until the pigment was not removed, and then dried to obtain a chitin powder containing an edible blue pigment.

30 mg of the obtained chitin powder was filled in a hard capsule made of gelatin, set in a nasal sprayer (trade name: Publyzer, manufactured by Ishikawa Seisakusho), and directly administered to the lower part of the lower turbinate of the subject. After the administration, changes in the state of the sprayed spray were observed with an endoscope over time. As a result, it was observed that the mucous membrane of the nasal cavity was covered until 2.5 hours later and gradually flowed deeper from 3 hours later. After 4.5 hours, no chitin powder was present in the lower nasal turbinate tip.

[Pyrogenic Substance Test] In order to test the presence or absence of pyrogenicity of the anti-inflammatory spray for nasal and oral cavities of the present invention, a pyrogenic substance test was carried out by the following method. To 12 g of the chitin powder having a diameter of 45 to 120 μm obtained by the method of Example 1 was added 120 ml of physiological saline (Otsuka Pharmaceutical Co., Ltd.) listed in the Japanese Pharmacopoeia, and the mixture was left at room temperature for 72 hours to obtain an extract. The extract was filtered through a 0.8 μm filter and heated to 37 ° C. to obtain a test solution. The body temperature of male Japanese white rabbits was measured three times at hourly intervals, and three specimens with small fluctuations in body temperature were used for the test. Using the body temperature before administration as a control body temperature, within 15 minutes after the measurement of the control body temperature, a test solution equivalent to 10 ml per 1 kg body weight of a rabbit is administered through the ear vein, and changes in body temperature are observed every hour until 3 hours later. did. The maximum value of the difference between the value and the control body temperature was defined as the temperature increase of the test animal. Table 1 shows the results.

[0030]

[Table 1]

From the above results, since there was no test animal whose temperature rise after injection was positive for pyrogenic substances or 0.6 ° C. or more, which is a reference for retesting, the nasal and oral cavity anti-inflammatory spray of the present invention was negative for pyrogenic substances. Was determined.

[Irritation Test] An irritation test on the nasal mucosa of the spray obtained by the method of Example 1 was carried out by continuous intranasal administration. That is, a tip for an Eppendorf pipette was attached to a nasal sprayer (trade name: Publyzer, manufactured by Ishikawa Seisakusho Co., Ltd.), and sprayed to the left nasal cavity of a rabbit fixed to a fixator at the time of administration. Spray amount 8mg / k each time
g twice daily for 30 consecutive days. As a result, in the nasal cavity to which the spray of Example 1 was administered, the nasal mucosa was not affected, and no suppression of weight gain and no decrease in adrenal weight were observed. On the other hand, a mixed powder of 5 μg of beclomethasone dipropionate and 8 mg of hydroxypropylcellulose was administered to the right nasal cavity of rabbits twice a day for 30 consecutive days per kg of the body weight of the sample. As a result, no effect was observed on the nasal mucosa, but a slight suppression of weight gain and a slight decrease in adrenal gland weight, presumably due to steroids, were observed.

Example 2 A hybrid dog having a pollen allergy in both nasal cavities (weight 5 kg)
Was sprayed with the spray obtained in Example 1 on the left nasal cavity. No treatment was performed in the right nasal cavity. As a result, it was found that the left nasal cavity to which the anti-inflammatory spray agent for nasal and oral cavity of the present invention was applied was calmed in the left nasal cavity, but was not calmed in the right nasal cavity.

Example 3 Chitin powder (manufactured by Sanei Kogyo Co., Ltd.) was dissolved in a solvent composed of dimethylacetamide and lithium chloride to obtain a solution having a chitin concentration of 8% by weight. The resulting solution was filtered through a 1400 mesh stainless net to obtain a chitin dope. 50 g of polyvinyl alcohol granules (UMR-10M, manufactured by Unitika Chemical Co., Ltd.) was added to 100 g of the chitin dope, mixed well, and cast on a glass plate. The cast was left for 2 hours, and when the cast was flattened to some extent, it was put into boiling water together with the glass plate to cure the chitin dope and dissolve and remove the polyvinyl alcohol. The resulting sponge was sufficiently washed with distilled water, freeze-dried, finely ground to some extent with a mixer, and further finely ground using a ball mill to produce a fine powder of chitin. The diameter of the obtained powder was measured with a universal projector (manufactured by Nikon Corporation, PROFILE PROJECTOR V-12, measurement magnification: 200 times) using 100 samples. The average and standard deviation of the particle size were 115 μm and 27.8 μm, respectively.
Met. The degree of deacetylation of the chitin fibers constituting the powder was 7%.

The effect of the thus obtained anti-inflammatory spray for nasal and oral cavity was confirmed by the following experiments. This drug was sprayed into the nose of a 8.3 kg adult dog with allergic rhinitis. A tip for an Eppendorf pipette was attached to a nasal sprayer (trade name: Publyzer, manufactured by Ishikawa Seisakusho Co., Ltd.) and sprayed to the left nasal cavity of a mongrel dog fixed to a fixator at the time of administration. The right nasal cavity received no treatment. As a result, while the inflammation had subsided in the nose to which the spray of the present invention was administered, the inside of the nose not using this agent was observed with an endoscope, and the inflammation continued.

[Intradermal Reaction Test] To 1.5 g of the chitin powder obtained in Example 3 was added 150 ml of physiological saline, extracted at 85 ° C. for 1 hour, and allowed to stand until it reached room temperature. This extract was injected intradermally into two Japanese male white rabbits, and an intradermal reaction test was performed. As a result, erythema, edema, bleeding, and necrosis were not recognized, and the result was negative, and safety was confirmed.

Example 4 A clinical test was conducted on 15 volunteer patients who developed hay fever. Chitin powder 30 obtained by the method of Example 3
mg in a capsule (size: capsule number 3, base: gelatin) listed in the Japanese Pharmacopoeia, set it in a nasal sprayer (trade name: Publyzer, manufactured by Ishikawa Seisakusho), and when you wake up and go to bed Each capsule was administered for one continuous week. Observing the degree of improvement in sneezing, nasal discharge, and nasal congestion, and determining whether it was significant improvement, improvement, slight improvement, invariance, or deterioration, the total improvement was 60%, and improvement was 80% or more. It has been clinically shown that this drug is effective as a nasal mucosal coating protective agent without side effects.

Example 5 Chitin powder (manufactured by Sanei Kogyo Co., Ltd.) was dissolved in a solvent composed of dimethylacetamide and lithium chloride to obtain a solution having a chitin concentration of 8% by weight. The resulting solution was filtered through a 1400 mesh stainless net. Chitin solution 1.5L and water
2.0 L was placed in a Multi-Blender Mill BL4 (manufactured by Nippon Seiki Co., Ltd.), stirred and mixed at 25 ° C. and 4000 rpm, and washed by coagulation to obtain chitin fibrils. The obtained chitin fibrils were pulverized with a ball mill in the same manner as in Examples 1 and 3, to obtain a nasal and oral anti-inflammatory spray.

The obtained anti-inflammatory spray for nasal and oral cavities was sprayed into the nose of a hybrid adult dog having allergic rhinitis and weighing 5.8 kg. As a result, while the inflammation had subsided in the nose to which the spray of the present invention was administered, the inside of the nose not using this agent was observed with an endoscope, and the inflammation continued.

Example 6 Using the chitin powder obtained in Example 5, the following test was conducted to clarify the sensory properties when administered intranasally. Take 40 mg of chitin powder with 90% or more particles having an effective particle size of 20 to 200 μm, fill a capsule (size: capsule number 3, base: gelatin) listed in the Japanese Pharmacopoeia, and use this capsule for nasal cavity. Sprayer (product name:
(Publicizer, manufactured by Ishikawa Seisakusho).
A 0.8 mm diameter needle was penetrated through the set capsule to make holes at both ends of the capsule, and then a rubber ball was pushed to send air, and chitin powder was ejected from the nozzle tip of the spray tool. The tip of this nozzle is inserted into the nasal cavity of 10 volunteers with pollinosis and sprayed alternately four times left and right, and 40 mg (total amount) of chitin is injected into the nasal cavity and its odor, irritation and adhesion to mucous membranes A sensory test was conducted on the sensation and foreign body sensation in the nasal cavity after absorbing water. As a result, all answered that the intranasal injection preparation of the present invention had little odor and irritation, so that it could be used continuously. In addition, the adhesion to the mucous membrane and the feeling of foreign body in the nasal cavity were good in all cases, and there was no particular problem. From the above results, it is clear that the spray for nasal and oral mucosa of the present invention has a good feeling in use.

Example 7 The chitin powder obtained in Example 5 was administered into a human mouth by the following method. Take 40 mg of chitin powder having an effective particle size of 130 μm and fill it into capsules (size: capsule number 3, base: gelatin) listed in the Japanese Pharmacopoeia. This capsule is used for a nasal sprayer (trade name: Publyzer) , Manufactured by Ishikawa Seisakusho Co., Ltd.). A 0.8 mm diameter needle was passed through the set capsule to make holes at both ends of the capsule. Insert the tip of the publisher nozzle into the mouth,
Chitin was administered to the inflamed site of the pharynx by pushing a rubber ball to blow air and ejecting chitin powder from the nozzle tip of the spray tool. As a result, the sensation of the throat was reduced.

Example 8 A chitin powder (manufactured by Sanei Kogyo Co., Ltd.) was dissolved in a solvent composed of dimethylacetamide and lithium chloride to obtain a solution having a chitin concentration of 8% by weight. The resulting solution was filtered through a 1400 mesh stainless net to obtain a chitin dope. The viscosity of this dope at 25 ° C. was 410 cps. 100 g of the chitin dope was dropped from a glass pipette having a tip diameter of 1.2 mm into a coagulation bath of 500 ml of methanol. The coagulation bath was gently stirred with a magnetic stirrer. The distance from the pipette tip to the coagulation bath was 10 cm and the temperature of methanol was 20 ° C. After stirring the chitin granules solidified by the coagulation bath in the coagulation bath for about another 30 minutes, 500 m
and stirred for about 30 minutes, and the same operation was further repeated twice to obtain chitin granules. The resulting chitin granules were perfectly spherical and about 3 mm in diameter. Put the chitin granules in a 500ml glass beaker,
Cover the upper part of the beaker with a nylon mesh, blow it with compressed air and dry it.
mg of dried chitin granules were obtained. The diameter of the dried chitin granules was about 0.6 mm. This was put in a ball mill and ground for about 12 hours, and classified to obtain a chitin powder having a particle size of 30 to 120 μm.

30 mg of the above powder was placed in a capsule (size: capsule number 3, base: gelatin) listed in the Japanese Pharmacopoeia, and set in a nasal sprayer (trade name: Publyzer, manufactured by Ishikawa Seisakusho Co., Ltd.). Then, a hole having a diameter of 0.8 mm was made, and the chitin powder was sprayed by an air flow. Observation of the state of spraying revealed the same appearance as when the fibers and sponge were pulverized. When administered to the nasal cavity of three volunteers who had a hot sensation in the nasal mucosa, the nasal mucosa was well covered and the inflammation was sedated.

Example 9 A dispersion of 100 mg of the chitin powder obtained in Example 8 dispersed in 10 ml of ethyl alcohol was placed in a 15 ml-capacity portable sprayer. When the above dispersion was sprayed into a nasal cavity of a patient with allergic rhinitis as an anti-inflammatory spray for the nasal cavity, the same effect as in Example 8 was obtained.

Example 10 100 mg of the chitin powder obtained in Example 8 was placed in a spray can having a capacity of 30 ml together with carbon dioxide to prepare an anti-inflammatory spray for oral cavity. The obtained oral anti-inflammatory spray was injected toward the pharynx of a patient having inflammation of the tonsils. When administration twice a day was continued for 2 days, the inflammation gradually subsided.

[0046]

The anti-inflammatory spray for nasal and oral cavity of the present invention has an excellent inflammation-relieving effect and a therapeutic effect on inflammation sites in various allergic symptoms such as hay fever, and can relieve inflammation in a short time. It is possible to do. Moreover, the anti-inflammatory spray for nasal and oral cavity of the present invention is also effective in preventing inflammation such as allergic rhinitis. Further, since the nasal and oral cavity anti-inflammatory spray of the present invention does not contain a steroid component, it can be safely used without worrying about side effects as seen in steroids.

 ──────────────────────────────────────────────────の Continued on the front page (72) Inventor Nobuyuki Tanimoto 23 Uji Kozakura, Uji-city, Kyoto Unitika Unit Research & Development Center (72) Inventor Ryoichi Tsuruya 23 Uji Kozakura Uji-city, Kyoto Unitika Research Inside

Claims (5)

[Claims] 1. An anti-inflammatory spray for nasal and oral cavities comprising chitin as an active ingredient. 2. The nasal and oral cavity anti-inflammatory spray according to claim 1, wherein the chitin is a powder. 3. The nasal and oral cavity anti-inflammatory spray according to claim 2, wherein the chitin powder is a powder obtained by pulverizing a chitin compact. 4. The nasal and oral cavity anti-inflammatory spraying agent according to claim 3, wherein the chitin molded product is in the form of any of fibers, fibrils, sponges and granules. 5. The chitin molded article is formed from a dope in which chitin is dissolved in a solvent.
Or the anti-inflammatory spray agent for nasal and oral cavity according to claim 4.