JP3068343B2 - Composition for diagnosing swallowing function - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a composition for diagnosing swallowing function, and more specifically to a dry gel composition for diagnosing swallowing function containing a detection reagent, wherein a predetermined amount of water is added and mixed at the time of use. It relates to a composition that gels.

2. Description of the Related Art Conventionally, as a method of diagnosing the swallowing function, a subject obtained by taking a liquid obtained by dispersing barium sulfate in water was observed by an X-ray, and the appearance of the dispersion passing through the esophagus was observed. Since the above-mentioned barium sulfate dispersion is in an aqueous sol state, there is a problem that a subject having a reduced swallowing function is less likely to cause swallowing reflex. Therefore, when the elderly or a patient with a reduced swallowing function swallows the barium sulfate dispersion, it is painful, and there is a risk that the dispersion may be erroneously aspirated into the trachea and choked. In general, it is known that swallowing reflex is more likely to occur in solid substances than in liquid substances, and the use of a gel-like test agent close to a solid instead of an aqueous sol test agent has reduced the swallowing function. Swallowing becomes easy for the subject, and there is little danger of the test agent being erroneously sucked into the trachea. Materials that can form a gel and can be administered include egg white,
Agar and natural polymers such as gelatin can be mentioned, but since the operation of heating or cooling after heating is necessary to form a gel of these natural polymers, a gel-like test agent containing the natural polymer is used. It was difficult to prepare at the time of use.
Therefore, a composition for diagnosing swallowing function that can be easily prepared at the time of use has been desired.

[0002]

Accordingly, an object of the present invention is to provide a composition capable of safely and efficiently diagnosing a swallowing function.

Means for Solving the Problems The present inventors have made intensive efforts to solve the above problems, and found that water is added to a dry gel composition containing a pregelatinized starch, a binder, and a detection reagent and mixed. In particular, the present invention has found that an aqueous gel composition can be produced at the time of use without requiring an operation such as heating, and that the swallowing function can be safely and efficiently diagnosed by using this aqueous gel composition. Was completed. That is, the present invention relates to 2
A dry gel composition for diagnosing swallowing function comprising 5 to 85% by weight of a detection reagent, 8 to 65% by weight of pregelatinized starch, and 0.5 to 2% by weight of a binder, wherein 1 part by weight of the composition is used. On the other hand, the present invention provides a composition which gels at a temperature of 40 ° C. or less when 1 to 9 parts by weight of water is added and mixed.

[0003] The pregelatinized starch used in the present invention is represented by X
A starch that does not show interference rings in the line, for example, a method of heating by adding water to starch granules, a method of treating with a swelling reagent such as a calcium nitrate or sodium hydroxide solution, or a method of converting starch into phosphorus oxychloride or the like. And etherification and esterification.
Further, the starch pregelatinized as described above is, for example, 80
Pregelatinized starch dried at a temperature of not lower than 15 ° C. to have a water content of 15% or less can also be used. Α preferably used in the present invention
Examples of the modified starch include, for example, those produced from corn starch by a hot roll method, and these can be obtained, for example, from Matsutani Chemical Industry Co., Ltd. The water content of these pregelatinized starches is usually 13% by weight or less, preferably 10% by weight or less, and the particle size is 150 μm or less.

The detection reagent contained in the dry gel composition of the present invention has no significant adverse effect on a subject,
If the reagent can be detected externally after administration,
Anything may be used. Examples of these detection reagents include contrast agents such as barium sulfate, iodine compounds, bismuth subnitrate, and bismuth subcarbonate, but the detection reagents used in the present invention are not limited to these. Further, two or more of these detection reagents may be used in combination. Of the above detection reagents, barium sulfate and iodine compounds are preferred. Examples of the binder contained in the dry gel composition of the present invention include hydroxypropylcellulose, hydroxypropylmethylcellulose, methylcellulose, polyvinylpyrrolidone and the like. Among the above binders, hydroxypropylcellulose and hydroxypropylmethylcellulose are preferred.

[0005] In the dry gel composition of the present invention, of the above components, the detection reagent is 25 to 85% by weight based on the total weight of the composition, the pregelatinized starch is 8 to 65% by weight, and the binder is 0.5%. It is a composition containing ２2% by weight. When the content of the detection reagent exceeds 85% by weight, the mixing ratio of the pregelatinized starch decreases, and a change in the amount of water to be gelled causes a problem that the change in the viscosity of the aqueous gel increases and the preparation becomes difficult. When the content of the detection reagent is less than 25% by weight, there arises a problem that the X-ray imaging ability of the aqueous gel is reduced. When the content of pregelatinized starch exceeds 65% by weight,
When the amount of water at the time of forming the aqueous gel increases, the problem that the content of the detection reagent decreases and the X-ray imaging ability decreases occurs, and when the content of the pregelatinized starch is less than 8% by weight,
There is a problem that the ability to form an aqueous gel is reduced. If the content of the binder exceeds 2% by weight, the dry gel composition becomes hard, and it takes a long time to prepare a uniform aqueous gel composition, and the content of the binder becomes 0.5% by weight. If it is less than 5, there is a problem that the dry gel composition cannot be granulated. The water content is usually 5% by weight or less based on the total weight of the composition. Preferred compositions include 75 to 85% by weight of the detection reagent, 10 to 2% by weight based on the total weight of the composition.
Mention may be made of compositions comprising 0% by weight of pregelatinized starch and 1-2% by weight of a binder. The dry gel composition of the present invention, when added and mixed with 1 to 9 parts by weight of water per 1 part by weight of the composition, swells at a temperature of 40 ° C. or lower, preferably at room temperature, and becomes bulky and gel. To give an aqueous gel composition. As used herein, the term “gelation” means that an aqueous composition obtained by adding and mixing water to the dry gel composition of the present invention has a structural viscosity as described above. Moreover, in this specification, normal temperature means the temperature of 15-25 degreeC. Also, the aqueous gel composition may exhibit thixotropic properties. In the present specification, the thixotropic property means that when a mechanical stress is applied to an aqueous gel composition in an isothermal state, the gel structure is destroyed and the viscosity is reduced.
If left for a while, the gel structure is regenerated again and the viscosity is recovered. The thixotropic property is, for example, by measuring the shear stress of the aqueous gel composition for each shear rate using a cone plate type rotary viscometer, and observing the change in viscosity of the aqueous gel composition with respect to the change in stress from its hysteresis curve. You can check.
The water to be added may be added to the dry gel composition at once, or may be added in several portions, and a uniform aqueous gel composition is obtained as quickly as possible over 1 to 5 minutes. Until they are mixed. Mixing may be performed at 40 ° C. or lower, preferably at room temperature, using a spoon or the like.

The aqueous gel composition obtained by adding and mixing 1 to 5 parts by weight of water with respect to 1 part by weight of the dry gel composition of the present invention may have a hardness of rice flour dango, The aqueous gel composition obtained by adding and mixing 1.5 to 7 parts by weight of water with respect to 1 part by weight of the dry gel composition of the present invention may have a hardness of about pudding. The aqueous gel composition obtained by adding and mixing 2 to 8 parts by weight of water with respect to 1 part by weight of the dry gel composition of the present invention may have a hardness of about yogurt. The aqueous gel composition obtained by adding and mixing 3 to 9 parts by weight of water with respect to 1 part by weight of the dry gel composition may have fluidity comparable to that of heavy water.
The rheological properties of the aqueous gel composition depend on the ratio of the amount of the dry gel composition to the amount of water added to the dry gel composition, as well as the type of pregelatinized starch (raw material of pregelatinized starch), the type of detection reagent, and the binding. It may vary depending on the amount of the agent and the like. An aqueous gel composition having various rheological properties is prepared by adjusting the amount of water to be added, and at least one aqueous gel composition having appropriate rheological properties is selected according to the swallowing ability of the subject, and this is selected. It may be administered orally to the subject.

[0007] 5-10 ml of the above aqueous gel composition is
Orally administered to the subject with a spoon 2 to 5 times as needed,
By detecting the detection reagent in the aqueous gel composition from outside the living body, the swallowing function of the subject can be diagnosed.
The detection reagent in the aqueous gel composition administered to the subject is X
It can be detected by means such as a line. By monitoring the detection reagent in the aqueous gel composition with the above-described detection means, it is possible to observe that the aqueous gel composition swallowed by the subject passes through the esophagus, and to diagnose the swallowing function of the subject from this observation result. Can be. When the subject has a function of sufficiently swallowing the aqueous gel composition, it can be observed that the aqueous gel composition passes through the subject's mouth, esophagus, and stomach in this order, but the subject has a sufficient swallowing function. If not, it is observed that some or all of the aqueous gel composition is aspirated into the trachea of the subject. When the aqueous gel composition is sucked into the trachea, it can be removed from the trachea by forcibly coughing. In addition, the swallowing ability of the subject is determined by swallowing the aqueous gel composition having different apparent viscosities in order from the one having the highest viscosity to the subject, and detecting which stage of the aqueous gel composition can be swallowed. Can be quantitatively diagnosed.

In the dry gel composition of the present invention, in addition to the above-mentioned components, excipients such as lactose and D-mannitol; glycols such as polyethylene glycol and glycerin as lubricants; thickening agents such as sodium carboxymethylcellulose and guar gum Agent: carbonate that foams when water is added at the time of use,
Bicarbonate or the like and an organic acid or the like may be added. Examples of the carbonate and hydrogen carbonate include potassium carbonate, sodium carbonate, calcium carbonate, and sodium hydrogen carbonate, and examples of the organic acid include citric acid, tartaric acid, and malic acid that are harmless in the amount used. Blowing agents are preferably used to bulk the aqueous gel. In addition, p
H regulators, stabilizers, flavoring agents, sweeteners, flavoring agents, coloring agents and the like may be added.

[0009] The dry gel composition of the present invention comprises 200 to 1
It is preferable to granulate so as to have a particle size of about 000 μm. Granulation can be carried out by a conventional method using an organic solvent, for example, alcohols such as ethanol and propanol, a mixture of chlorinated hydrocarbons such as methylene chloride and alcohols, or a mixture of these organic solvents and water. . The granulated dry gel composition of the present invention is preferable because gelation occurs very easily when water is added at the time of use.
The dry gel composition of the present invention usually contains 5%
Water content of not more than 3% by weight at the time of granulation.
As a method for producing the dry gel composition of the present invention, for example, mixing powder by rotating a blade attached to a rotating shaft,
Kneading may be performed as follows using a high-speed stirring granulator (for example, NGSD-350 manufactured by Daiwa Kakoki Co., Ltd.) capable of performing particle processing by coagulation, shearing, rolling, and sizing. That is, after filling a predetermined amount of a detection reagent as a raw material, pregelatinized starch, and an optionally added excipient into a stirring tank, mixing is performed by rotating the blade at about 50 to 200 times per minute, Further, after adding a predetermined amount of a binder, the number of rotations of the blade is increased to about 200 to 500 rotations per minute according to the degree of granulation to produce a granulated material.
The dried gel composition of the present invention can be produced by sizing the granules dried at 0 ° C. for about 5 to 8 hours with a blow dryer.

[0010]

The dry gel composition of the present invention gives a uniform aqueous gel composition when a predetermined amount of water is added and mixed. A swallowing function of a subject can be diagnosed by orally administering an aqueous gel composition having appropriate rheological properties to a subject and detecting a detection reagent in the aqueous gel composition. In addition, the preparation of the aqueous gel composition has the advantage that it can be performed in a short time at the time of use, and the operation is extremely simple because no operation such as heating is required. Also, by increasing or decreasing the amount of water added from the same dry gel composition, aqueous gel compositions having various rheological properties can be produced, and the degree of the swallowing ability of a subject using these aqueous gel compositions can be increased. Can be diagnosed. Furthermore, the obtained aqueous gel composition is capable of quantitatively diagnosing the degree of the swallowing ability of the subject by administering the composition in order of increasing apparent viscosity, and the aqueous gel is placed in the trachea of the subject. The risk of the composition being erroneously sucked can be reduced, and the swallowing function can be safely diagnosed even for the elderly and patients with reduced swallowing function.
Hereinafter, the present invention will be described more specifically with reference to examples, but the present invention is not limited to these examples.

[0011]

【Example】

[Example 1] A high-speed stirring granulator (NGSD-350 manufactured by Daiwa Kakoki Co., Ltd., capacity: New Grass Machine) in which the blades are set so that they are orthogonal to each other in the order of the scraper blade and the flat blade (each two blades) from below the rotating shaft. 33 liters) to produce the dry gel composition of the present invention. After filling a predetermined amount of the detection reagent and the pregelatinized starch into the stirring tank, the blades were rotated at 50 revolutions per minute for mixing for 2 minutes, and then the rotation speed was increased to 200 times / min, followed by further mixing for 3 minutes. . Next, the number of rotations is set to 20
The binder was added while maintaining the rate at 0 times / minute, and the addition of the binder was completed within 5 minutes. After adding the binder, the rotation speed is gradually increased from 200 rotations per minute to 500 rotations,
Granulation was completed in 10 minutes, and the granulated product was collected. The granulated product was dried at 60 ° C. for 4 to 6 hours using a blow dryer (shelf type), and then sieved with an 850 μm sieve to obtain a dry gel composition of the present invention. The number and composition of each formulation are shown in Table 1 below.

[0012]

[Table 1] Formulation No. 1 2 3 4 5 6 7 Detection reagent Barium sulfate 850 mg 850 850 850 250 500 750 Pregelatinized starch matsunoline W ¹⁾ 90 mg 100 110 120 650 400 150 Binder HPC ²⁾ 10 mg 10 10 10 12.5 12.5 8 Lactose-- --50 50 50 D- Mannit 100mg 90 80 70 37.5 37.5 42 1) Matsunoline W: pregelatinized starch of wheat starch manufactured by Matsutani Chemical Industry Co., Ltd. 2) HPC: hydroxypropyl cellulose manufactured by Shin-Etsu Chemical Co., Ltd.

Various aqueous gel compositions were prepared by adding various amounts of water to the above dry gel formulations. The rheological properties of the obtained aqueous gel composition were determined under the following conditions. Equipment used: Rheometer NRM-120 type (cone plate type rotary viscometer manufactured by Nippon Rheological Instruments Co., Ltd.) Standard solution for viscometer calibration: JIS Z9909 JS200 (Lot.24) Showa Shell Sekiyu KK Measurement conditions Measurement temperature: 20 ° C Shear rate: 1800 s ^-1 (100 rpm) Program time: 60 seconds Sample preparation method: A predetermined amount of water is added to the dry gel preparation, and the mixture is stirred and kneaded with a spatula for 2 minutes. Measurement time: 60 minutes after sample preparation After one minute Measurement method: The following quantities were read from a flow curve (hysteresis curve) obtained with a program time of 60 seconds and a maximum rotation speed of 100 rpm. (1) Apparent viscosity (unit: cP) Max: Apparent viscosity when rotation speed reaches 100 rpm 1/3: Apparent viscosity 20 seconds after start of measurement (2) Plastic viscosity (unit: cP) Max: Flow curve 1/3: Viscosity obtained from the yield point (intersection between the falling part of the flow curve and the shear stress axis) and the flow curve point measured 20 seconds after the start of the measurement (3) Bingham yield value ( (Unit: Pa): Yield stress obtained by extending the descending part of the flow curve to the shear stress axis. Further, the following value is calculated from the above amounts. (4) Ratio (1): Apparent viscosity (1/3) Viscosity (Ma
x) (5) Ratio (2): value obtained by dividing plastic viscosity (1/3) by plastic viscosity (Max). The results are shown in Tables 2 to 8 below. After the viscosity was measured by applying a shear stress of 100 rpm as described above, when the aqueous gel composition was left for a while, the recovery of the viscosity was recognized.

[0014]

[Table 2]

[0015]

[Table 3]

[0016]

[Table 4]

[0017]

[Table 5]

[0018]

[Table 6]

[0019]

[Table 7]

[0020]

[Table 8]

Example 2 Formulation No. 1 of Example 1 2 of 2
60 ml of water was added to 0 g, and the mixture was stirred and kneaded with a spoon for 2 minutes to prepare a uniform aqueous gel composition a. The aqueous gel composition a had fluidity comparable to that of heavy water. Aqueous gel composition a was orally administered to patient A who had been treated with tube feeding using a spoon. Observation with an X-ray camera showed that the aqueous gel composition a moved inside the patient A. Since the aqueous gel composition a orally administered to the patient A was erroneously aspirated into the trachea, it was diagnosed that the patient A had difficulty swallowing a substance similar to the aqueous gel composition a. Example 3 Formulation No. of Example 1 2 20g water 20
ml and 30 ml, respectively, and kneaded with a spoon for 2 minutes with stirring to prepare uniform aqueous gel compositions b and c. The aqueous gel composition b had a hardness of about rice flour dango, and the aqueous gel composition c had a hardness of about yogurt. 2
Aqueous gel compositions b and c were sequentially divided into four times and orally administered using a spoon to patient B who had been treated by tube feeding until the day before. When the state of the aqueous gel composition b moving in the body of the patient B was observed with an X-ray camera, the aqueous gel composition b moved in the order of the oral cavity, the esophagus, and the stomach, and did not enter the trachea. When the same observation was performed for the aqueous gel composition c, similar results were obtained. From these results, it was diagnosed that the patient B had a sufficient swallowing ability for food having the hardness of the aqueous gel compositions b and c.

──────────────────────────────────────────────────続 き Continued on the front page (58) Fields surveyed (Int.Cl. ⁷ , DB name) A61K 49/04 A61K 9/10 A61K 9/14 A61K 47/36 CA (STN) EMBASE (STN) MEDLINE (STN )

Claims (6)

(57) [Claims] 1. 25 to 85% by weight based on the total weight of the composition
, A detection reagent of 8 to 65% by weight of pregelatinized starch, and 0.
A dry gel composition for diagnosing swallowing function comprising 5 to 2% by weight of a binder, wherein 1 to 9 parts by weight of water is added to and mixed with 1 part by weight of the composition, and the gel is obtained at a temperature of 40 ° C or lower. Composition to be converted. 2. The dry gel composition for diagnosing swallowing function according to claim 1, wherein the gelled composition exhibits thixotropic properties. 3. The composition of claim 1, wherein 1 to 9 parts by weight of water is added to and mixed with 1 part by weight of the composition to form a gel at room temperature.
A dry gel composition for diagnosing swallowing function according to the above. 4. The dry gel composition for swallowing function diagnosis according to claim 1, which is granulated. 5. The dry gel composition for diagnosing swallowing function according to claim 1, wherein the detection reagent is a contrast medium and used for X-ray diagnosis. 6. The detection reagent according to claim 5, wherein the detection reagent is barium sulfate.
A dry gel composition for diagnosing swallowing function according to the above.