JP3231276B2 - Chitosan composition and method for producing the same - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

[0001] The present invention relates to a chitosan composition and a method for producing the same.

[0002]

2. Description of the Related Art Chitosan exhibits various physiological activities such as a fat absorption inhibitory effect, a cholesterol-lowering effect, a blood pressure lowering effect, a blood uric acid level lowering effect, and a heavy metal adsorption ability. I'm advancing. Such a chitosan powder has a low bulk specific gravity and poor powder fluidity, so that when a large amount of chitosan is blended, the filling amount is limited in the form of granules, tablets, hard capsules and the like. As a method of raising the bulk specific gravity and improving the powder fluidity, a granulation method using a binder such as a thickening polysaccharide, starch, a cellulose derivative and a solvent such as water or an aqueous ethanol solution as conventionally performed is used. The more chitosan incorporated, the more brittle the granules. Particularly, when processing into tablets, the bulk specific gravity is small and the moldability is poor, so that there is a limit in weight adjustment, and there is a problem that tablets with high friability are obtained.

[0003] In addition, tablets containing 30% by weight or more of chitosan are not sufficiently disintegrated by stomach acid, migrate into the intestine while the tablet surface is gelled, and are excreted in stool as it is. Such a phenomenon has been observed, and particularly, as the chitosan content increases, such a tendency increases. JP-A-8-26 discloses a method for improving the physical properties of chitosan.
9104 and JP-A-60-130346 are known, but when a large amount of chitosan is blended for tableting, there is no improvement in the drawbacks such as low bulk specific gravity and poor moldability. JP-A-62-193638 discloses a granule containing an organic acid salt of chitosan, which improves the processability (bulk specific gravity and moldability) of granules, tablets, capsules, and the like. There is no solution to improve the disintegration of tableting products with gastric acid.

[0004]

DISCLOSURE OF THE INVENTION The present invention solves problems such as low bulk specific gravity, poor fluidity, and brittle granules after granulation, which occur when chitosan is contained in a high content. An object of the present invention is to provide a chitosan composition having improved disintegration with gastric acid when processed.

[0005]

Means for Solving the Problems The present inventors have found that it is effective to add calcium and fruit juice to chitosan in order to solve these problems, and have completed the present invention. That is, the present invention is a chitosan composition comprising chitosan, a natural calcium-rich material or a purified calcium material, and fruit juice.

[0006]

BEST MODE FOR CARRYING OUT THE INVENTION The chitosan referred to in the present invention is a polymer in which glucosamine obtained from shells such as shrimp and crab, and squid shells as raw materials is β1,4 bonded. Specifically, the shells of shrimp, crab, etc. are washed with water and dried,
If necessary, crush. The shell powder is subjected to a dilute hydrochloric acid or EDTA treatment to perform a demineralization treatment. Next, the crust from which ash has been removed is boiled with an aqueous sodium hydroxide solution to carry out a protein removal operation. Chitin, which is a polymer of N-acetylglucosamine obtained through these steps, is converted into, for example, 3
What is obtained by deacetylation treatment with a 0 to 50% concentrated aqueous sodium hydroxide solution is chitosan.

[0007] The naturally occurring calcium-rich or purified calcium material used in the present invention includes, for example, shell calcium (scallop calcium, oyster shell calcium, etc.), eggshell calcium, coral calcium,
All natural calcium that can be used in foods such as sea urchin shell calcium, petrified seaweed calcium, pearl calcium, bovine bone calcium, fish bone powder calcium, fish scale calcium, milk calcium, and purified calcium carbonate, calcium phosphate, calcium lactate, glucone All calcium materials that can be used in foods, such as calcium acid, calcium citrate, and calcium chloride. In the present invention, these natural calcium-rich materials or purified calcium materials can be used alone or
More than one species can be used in combination.

[0008] A general method for producing a calcium-rich material produced from nature is a series of flows in which raw materials are selected, crushed, sieved, heat sterilized, and the like, and then ground to a predetermined particle size. I have. For example, in a general method for producing scallop calcium, it is produced by sorting, crushing, and sieving, followed by dry heat sterilization at, for example, 200 ° C., and pulverization to a predetermined particle size.
In general, coral calcium is generally obtained by first collecting coral sand or coral fossils, removing foreign substances after washing with water, and then sterilizing and drying by heating at, for example, 100 ° C. or more, to a predetermined particle size. It is manufactured by a method of pulverizing so as to be.

Next, of the purified calcium materials, for example, calcium carbonate, calcium oxide obtained by calcining limestone is reacted with water to form calcium hydroxide, and then colloidal or light calcium carbonate is passed through carbon dioxide gas. A method of obtaining, or a method of reacting a sodium carbonate solution with a calcium chloride solution to precipitate calcium carbonate,
Alternatively, there is a method in which natural limestone is pulverized into heavy calcium carbonate. Further, there is a purified calcium material obtained by reacting calcium carbonate or calcium oxide with various acidic solutions. For example, calcium citrate is generally produced by dissolving citric acid in water, neutralizing with calcium oxide, purifying, collecting a precipitate, and drying. In general, calcium lactate is produced by adding calcium carbonate as a neutralizing agent during lactic acid fermentation to obtain crude calcium lactate and collecting and purifying it, or by adding calcium carbonate to synthetic lactic acid.

[0010] The fruit juice used in the present invention is lemon, sudachi, citron, kabos, orange, grapefruit, hassaku, summer tangerine, lime, sweetie, shikuwasha, raspberry, cranberry, blueberry, gooseberry, aronha, currant, acerola. ,plum,
All fruit juices that can be used in foods such as apples, peaches, grapes, pears, strawberries, apricots, passion fruits, pineapples, guava, cam cam, etc. These can be used alone or in combination of two or more. The fruit juice to be used may be one obtained by washing the selected fruit and crushing it and then squeezing it as it is, or crushing it and then squeezing it through steps such as destemming and heating. There are various methods for squeezing, such as a method using a press and a method using centrifugal separation. Further, any juice such as concentrated juice, concentrated turbid juice, and transparent concentrated juice can be used, and the pH value of the juice is preferably 4 or less, more preferably 3 or less. Even fruit juice having a pH of more than 4 can be preferably used by adjusting the pH to 4 or less with an organic acid. When a juice having a pH of more than 4 is used, the dissolution of chitosan is insufficient, and the binding between the particles is weakened. As a result, granules obtained by granulation and drying tend to have a low bulk specific gravity and become brittle. It is in.

In the present invention, the compounding amount of the high calcium content or the purified calcium material produced from nature is preferably 3 to 2 parts per 100 parts by weight of chitosan.
The amount of fruit juice is preferably 10 to 300 parts by weight, more preferably 15 to 50 parts by weight. When the amount of the calcium material is less than 3 parts by weight based on 100 parts by weight of chitosan,
Tablets of the chitosan composition tend to have poor disintegration with gastric acid, and if the amount exceeds 200 parts by weight, the texture tends to be poor. The amount of fruit juice added is 1 per 100 parts by weight of chitosan.
If the amount is less than 0 parts by weight, unevenness may occur in the impregnation of chitosan with fruit juice, the bonding between particles is insufficient, the amount of fine powder increases, and the bulk specific gravity tends to decrease. When this is processed into a tablet, it tends to be broken as soon as it is contained in the mouth, making it difficult to swallow. If it exceeds 300 parts by weight, it takes a long time to dry the granulated material.

As a method for producing the chitosan composition of the present invention, for example, after uniformly mixing chitosan and a high calcium content material or a purified calcium material produced from nature, fruit juice is dropped or sprayed on the mixed powder. While stirring and kneading, granulation is performed. In this case, the mixed powder containing chitosan forms so-called lumps, and the juice is sufficiently uniformly impregnated and kneaded with chitosan so as not to be in a non-uniform wet state. The obtained granulated product is usually dried so that the loss on drying is 10% or less. However, the granulated product may be dried after being sized to a predetermined particle size while being wet, or the wet granulated product may be dried. There is no problem even if the particle size is adjusted to a predetermined particle size later.

[0013] The high calcium content or the purified calcium material has good disintegration with gastric acid even if a part or the whole is added after adding fruit juice to chitosan, granulating and drying. It is possible to make chitosan tablets.

As the granulation method, wet granulation is appropriate, and specifically, a stirring granulation method, an extrusion granulation method, a crushing granulation method and the like are effective. The stirring granulation method is a method in which mixing, kneading, and granulation of powder are simultaneously performed in a closed structure by rotating a stirring blade at a high speed in a mixing tank while adding a binder solution. It is. The extrusion granulation method is a method in which a kneaded wet mass is forcibly extruded from a screen of an appropriate size by a method such as a screw method or a basket method. The crushing and granulating method is a method in which a kneaded wet mass is sheared and ground by a rotary blade of a granulator, and is repelled from an outer peripheral screen by centrifugal force.

The drying method of the granulated material is hot air heating type (shelf drying, vacuum shelf drying, fluidized bed drying), conduction heat transfer type (flat pot type,
The effect of the present invention can be obtained by any method such as a tray box type or a drum type) or freeze-drying. The hot-air heating type directly contacts a material with hot air and simultaneously removes evaporated water, and the conduction heat transfer type indirectly heats the material through a heat transfer wall. Lyophilization means that the material is -1
Keep frozen at 0-40 ° C and then under high vacuum (2-
This is a method in which water is sublimated and removed by heating at 0.1 Torr).

According to the present invention, hard granules having a large bulk specific gravity can be easily produced. Tablets obtained by tableting using these granules have the effect of improving the disintegration of chitosan in gastric juice and increasing the solubility. Chitosan dissolves in gastric juice, making it fully in contact with fat, cholesterol, heavy metals, etc.
It adsorbs or wraps cholesterol, heavy metals, etc. and excretes them in the stool. Therefore, increasing the solubility of chitosan in gastric juice effectively inhibits various physiological activities of chitosan, such as fat absorption inhibitory effect, hypocholesterolemic effect and blood pressure lowering effect, blood uric acid level lowering effect, and heavy metal adsorption ability. It is useful in expressing. The mechanism of the effect of enhancing the disintegration of the tablet obtained in the present invention in gastric juice is not necessarily clear, but probably the calcium contained in the chitosan composition obtained by the present invention is ionized in gastric juice. It is speculated that the binding of the chitosan composition particles is likely to be easily broken and broken.

In the present invention, the point is to uniformly impregnate the mixed powder of chitosan and a calcium-rich material produced from nature or a purified calcium material by the juice, and the granules produced by the granulation method and the drying method are used. Physical properties are not affected.

If necessary, the chitosan may be mixed with other excipients, or the fruit juice may be mixed with, for example, xylitol,
It is preferable to use a solution in which a saccharide such as maltitol or lactitol is dissolved, because the bulk specific gravity becomes larger and harder granules are produced. The chitosan composition according to the present invention can be used, for example, as a chitosan-containing food, as an additive for health foods such as granules, hard capsules and tablets, and foods and drinks.

[0019]

EXAMPLES The present invention will be specifically described below with reference to examples, but the present invention is not limited to these examples. In the following,% is based on weight. In the examples, a stirring granulation method and a vacuum shelf drying method were employed.

Example 1 The following raw materials were prepared. Chitosan 85% Xylitol 4% Scallop shell calcium 8% Rapeseed oil and fat powder (after addition) 3% After mixing the above ingredients except rapeseed oil and fat powder, stir juice of pH 2.4 with stirring to 100 parts by weight of the ingredient mixed powder with stirring. 30 parts by weight. Under high vacuum conditions (2-0.1
Torr), dried at 60 ° C. for 1 to 3 hours so that the loss on drying was 10% or less, rapeseed oil and fat powder was added, and the mixture was tableted.

Example 2 After mixing the raw materials described in Example 1 except for rapeseed oil and fat powder, 30 parts by weight of a peach nectar adjusted to pH 3.0 with malic acid while stirring was added to 30 parts by weight of the raw material mixed powder. Was added dropwise. Under high vacuum conditions (2-0.1 Torr), 60
After drying for 1 to 3 hours so that the loss on drying was 10% or less at ℃, rapeseed oil and fat powder was added and the mixture was tableted.

Comparative Example 1 The following raw materials were prepared. Chitosan 85% Xylitol 4% Cellulose 8% Rapeseed oil / fat powder (post-addition) 3% After mixing the above-mentioned raw materials except rapeseed oil / fat powder, 30 parts per 100 parts by weight of raw material juice of pH 2.4 are mixed with stirring. Parts by weight were added dropwise. Under high vacuum conditions (2-0.1
Torr), dried at 60 ° C. for 1 to 3 hours so that the loss on drying was 10% or less, rapeseed oil and fat powder was added, and the mixture was tableted.

Comparative Example 2 After mixing the raw materials described in Example 1 except rapeseed oil and fat powder, 30 parts by weight of distilled water (pH 5.6) was added dropwise to 100 parts by weight of the raw material mixed powder while stirring. Under high vacuum conditions (2
After drying for 1 to 3 hours at 60 ° C. so that the loss on drying was 10% or less, rapeseed oil and fat powder was added and the mixture was tableted.

Example 3 After mixing the raw materials described in Example 1 except rapeseed oil and fat powder, a peach nectar of pH 4.2 was added to the raw material mixed powder 1 while stirring.
30 parts by weight were added dropwise to 00 parts by weight. 10% loss on drying at 60 ° C under high vacuum conditions (2-0.1 Torr)
After drying for 1 to 3 hours as described below, rapeseed oil and fat powder was added and tableted.

1. Disintegration test A test was performed based on the Japanese Pharmacopoeia. The first solution was used as a test solution. 2. Angle of repose Measured by the injection method. 3. Bulk specific gravity The granules were dropped into a graduated 100 ml container, and the weight was measured to calculate the weight per 1 ml. 4. Texture A sensory test was conducted on the feeling of dissolution of the mouth when the tablet was contained in the mouth. In Table 1, ○ indicates that there is no particular problem in taking the drug, X indicates that the tablet collapses immediately in the mouth and is difficult to drink, and Δ indicates the middle.

[0026]

[Table 1]

[0027]

In the case of Comparative Example 1, which does not contain a naturally-occurring high calcium content such as scallop shell powder, the processed tablet does not disintegrate in stomach acid. Further, in Comparative Example 2 out of the scope of the present invention using distilled water instead of fruit juice during granulation, the bulk specific gravity of the granules after granulation is small,
When it is processed into tablets, it disintegrates as soon as it is put into the mouth, which makes it difficult to drink and has poor fluidity. Example 3 using a peach nector having a pH of more than 4 has slightly better performance than Comparative Example 2, but is not sufficient. In contrast,
In Examples 1 and 2, which are within the preferred range of the present invention, using a fruit juice having a high calcium content produced from nature and having a pH of 4 or less, these properties are all excellent. Therefore, according to the present invention, it is possible to solve the problems that could not be solved by conventional techniques such as the case where a high content of chitosan was added, the bulk specific gravity was small, the fluidity was poor, and the granules after granulation were brittle. It is also possible to improve the disintegration with gastric acid when processed into tablets.

──────────────────────────────────────────────────続 き Continued on the front page (51) Int.Cl. ⁷ Identification code FI A61K 9/20 A61K 9/20 9/48 9/48 31/722 31/722 47/46 47/46 (56) References Features JP-A-7-194316 (JP, A) JP-A-5-255094 (JP, A) JP-A-6-22727 (JP, A) (58) Fields investigated (Int. Cl. ⁷ , DB name) A61K 47 / 36,9 / 16 A23L 1 / 30,1 / 304

Claims (6)

(57) [Claims] 1. A chitosan- containing tablet or granule comprising chitosan, a natural calcium-rich or purified calcium material, and fruit juice.
Or hard capsules . 2. A chitosan-containing tablet of claim 1, wherein the chitosan or calcium-rich substance is produced from chitosan and natural or purified calcium materials comprising the step of uniformly impregnated juice, granules Or c
Manufacturing method of hard capsules . 3. Impregnated with 100 to 300 parts by weight of chitosan and 3 to 200 parts by weight of a calcium-rich material or a purified calcium material produced from nature and 10 to 300 parts by weight of fruit juice, and dried. Chitosan- containing tablets
Preparations, granules or hard capsules . 4. Juice is added to 100 parts by weight of chitosan in 10 to 3 parts.
A chitosan- containing tablet, granule or hard capsule prepared by impregnating with 00 parts by weight, drying and then adding 3 to 200 parts by weight of a high calcium content or a purified calcium material produced from nature. 5. The chitosan- containing tablet according to claim 1, 3 or 4 , wherein the fruit juice is a fruit juice of pH 4 or less or a fruit juice adjusted to pH 4 or less by adding an organic acid. , Granules or hard capsules . 6. A chitosan-containing food using the chitosan- containing tablet, granule or hard capsule according to claim 1, 3 , 4 or 5.