JPH0653668B2 - Composition for treating schizophrenia - Google Patents

Description

TECHNICAL FIELD The present invention relates to a composition for treating schizophrenia. More specifically, it relates to a composition for treating schizophrenia, which contains an oyster meat extract as an active ingredient.

[Problems to be solved by the prior art / invention]

The biochemistry of schizophrenia has been chaotic for a long time, but in recent years it has been proved that the zinc content in the body is low.

Therefore, it has been attempted to treat schizophrenia by administering inorganic zinc or organic zinc (eg, zinc glutamate, zinc aspartate, etc.), but the zinc compounds that have been tried so far still cure schizophrenia. The fact is that the amount of zinc in brain tissue has not been increased.

[Problems to be solved by the invention]

Under such circumstances, there is a great demand for the development of a composition that easily crosses the blood-brain barrier to increase the zinc content in brain tissue and thus cure schizophrenia.

Therefore, it is an object of the present invention to provide new compositions for the treatment of schizophrenia.

[Means for solving problems]

The present inventors have conducted various studies in order to achieve the above-mentioned object, and have found that the oyster meat extract can cure schizophrenia. That is, when oyster meat extract was administered to a schizophrenic patient, delusions, hallucinations, thought disorders,
Symptoms such as apathy of emotions, decline of intention, abnormality of idea association and ego disorder disappeared.

This is because the main biochemical reaction of brain energy, that is, the active ingredient of carbonic anhydrase, which catalyzes the final chemical reaction of glycolysis, is supplemented with zinc, and the production of carbon dioxide gas is restored to normal. It is speculated that there will be.

Furthermore, dopamine-β-hydroxylase, which is an enzyme when dopamine generated from tyrosine produces catecholamines, uses copper as an active element, but due to this copper excess, catecholamines are made in large amounts to enhance the functions of various endocrine glands, and It is presumed that it is a psychotic symptom, but since zinc is an antagonist of copper, if zinc passes through the blood-brain barrier and reaches the brain pulp, copper is excreted and the dopamine-β-hydroxylase activity is normal. The present inventor speculates that the morbid symptom may be resolved by returning to the above.

The present invention has been completed based on the above findings, and relates to a composition for treating schizophrenia, which contains an oyster meat extract as an active ingredient.

Oysters belong to the family Bivalvia and the family Scutellariae and have been used for food.

In the present invention, this oyster extract is used as an active ingredient of a composition for treating schizophrenia.

In the present invention, the oyster meat extract is preferably an extract containing zinc (particularly in oyster meat extract powder)
0.02 to 0.1% by weight, preferably 0.03 to 0.08% by weight, more preferably about 0.05 to 0.07% by weight of zinc), for example, hot water extract of oyster meat (preferably, the hot water extract is further subjected to alcohol fractionation). (Precipitate obtained by subjecting to oyster meat), enzymatic decomposition products of oyster meat, and the like are used. Such an extract may be a suspension in a solvent (for example, water, alcohol, a mixed solution thereof, or the like), or a dried product thereof.

In the present invention, the temperature of the hot water for obtaining the hot water extract of oyster meat is usually about 50 to 90 ° C, preferably 70 to 8 ° C.
It is about 5 ° C., and can be obtained by heat extraction for 2 to 3 hours. The hot water extract may be used as it is as an active ingredient of the present invention, and an aqueous solution of the hot water extract (a hot water extract of oyster meat or a solid hot water extract dissolved in water) is subjected to alcohol fractionation. The obtained precipitate may be used as the active ingredient of the present invention.

The hot water extract aqueous solution is preferably adjusted to a solid content of 20 to 45 (w / w)% before being subjected to alcohol fractionation. The adjustment may be performed by a method known per se such as concentration.

Ethanol is preferably used as the alcohol used for the alcohol fractionation. The alcohol fraction is usually
It is carried out at a final concentration of 40 to 80 (w / w)%. The alcohol fractionation treatment time is usually 5 to 168 hours, preferably 48 to 96 hours.

As the enzymatically decomposed product of oyster meat, an enzyme-decomposed extract obtained by decomposing oyster meat with an enzyme, for example, a protease, particularly a neutral protease originating from Aspergillus or a actinomycete protease is used.

In particular, even in the oyster meat extract of the present invention, those having a zinc chelate compound having metal zinc and taurine as main constituents having the following characteristics are richer, such as the zinc chelate compound in oyster meat extract powder, Usually 0.1% by weight or more, preferably 0.3% by weight or more,
More preferably 1% by weight or more, particularly preferably 2% by weight
Those containing the above are effective.

The molecular weight measured by gel filtration analysis using Sephadex is 5,000 or less.

Taurine and zinc are the main constituents.

Here, it is preferable that the molar ratio of taurine is 20 and the molar ratio of zinc is 1.

Ninhydrin reaction positive.

Water soluble.

UV absorption: maximum absorption at 270 to 280 nm The zinc chelate compound is, for example, separated from the solid solution of the hot water extract and subjected to gel filtration to obtain a molecular weight of 5,000.
It can be obtained by collecting the following fractions.
In addition, the enzymatic decomposition extract was subjected to gel filtration to obtain a molecular weight of 5,00.
It can also be collected by collecting fractions of 0 or less.

The gel filtration carrier used in the above has a molecular weight of 5,000.
Any of the following substances can be preferably used as long as they can carry out molecular sieving. Specific examples include Sephadex G100 or Sephadex G75 and Sephadex G25.
And the like are exemplified. In the composition for treating schizophrenia of the present invention, it is not necessary to use the zinc chelate compound as a pure product, as long as the zinc chelate compound is rich. Therefore, for example, a membrane capable of separating a substance having a molecular weight of 100,000 or less, for example, an ultrafiltration membrane made of polyolefin, synthetic polymer (polysulfone, etc.), polyimide, etc.
You may use the said zinc chelate compound rich fraction which passes 351-P18LP (made by Nitto Denki Kogyo Co., Ltd.) etc. Moreover, the said fraction may be mix | blended with the above-mentioned oyster meat extract.

The characteristics of the zinc chelate compound are measured as follows.

(1) Molecular weight The molecular weight was measured under the following conditions by gel filtration using Sephadex G100 and Sephadex G-10. Its molecular weight is 5,000 or less.

Conditions: Column size: 20 mm x 1,000 mm Solvent: 0.2 M-NaCl Development speed: 1.5 ml / min. The molecular weights of bacitracin and insulin B are known.
It was decided by comparison with the chain.

(2) Constituents Amino acid analysis: A sample dissolved in 6N-HCl was put under reduced pressure in a decomposition tube, and heated with a heating lock (Hitachi Ltd.) at 110 ° C.
It was hydrolyzed for a period of time, concentrated to dryness, skipped with hydrochloric acid, dissolved in a sodium citrate solution, and injected into high performance liquid chromatography for examination.

Zinc analysis: A sample was wet-ashed according to a conventional method, and then Shimadzu AA-640
The analysis was performed with a -12 type atomic absorption spectrometer. As a result, the molar ratio of taurine and zinc was 20: 1.

(3) Ninhydrin reaction positive (4) Water-soluble (5) Ultraviolet absorption When ultraviolet absorption was measured by a conventional method using a self-recording spectrophotometer UV240 type manufactured by Shimadzu Corporation, it was 270-280.
It showed a maximum absorption at nm.

The oyster meat extract, which is the active ingredient of the present invention, is preferably used in the present invention after being recovered from the oyster meat and then dried by, for example, a spray dryer, a drum dryer or freeze-drying.

[Action / effect]

The composition for treating schizophrenia of the present invention is particularly useful, for example, as a therapeutic agent for, for example, melon schizophrenia.

The composition for treating schizophrenia of the present invention may be used in combination with other therapeutic agents for schizophrenia in addition to the oyster meat extract. In particular, when the composition for treating schizophrenia of the present invention is used for the treatment of delusional schizophrenia, its effect is remarkably increased by concomitant use with, for example, a chlorpromazine drug.

The composition for treating schizophrenia according to the present invention can be prepared into a medicine or the like by mixing the active ingredient, oyster meat extract, with conventional pharmaceutical additives, food additives and the like. As a method of administering the composition of the present invention, a general method in the field, that is, oral (in the form of tablets, capsules, granules, syrups, etc.) and the like are generally applied. The dosage may be an amount sufficient to treat schizophrenia, and may vary depending on, for example, symptoms, administration route, dosage form, etc. 120 mg / kg body weight / day is preferred.
The frequency of administration can be appropriately selected within the range of 1 to 4 times a day. The daily dose and administration schedule can be appropriately selected depending on the patient, symptom and the like.

Examples of additives (particularly carriers) for pharmaceutical preparations include shellac, gelatin, gum arabic, polyvinyl alcohol, polyvinylpyrrolidone, sodium alginate, methylcellulose, carboxymethylcellulose, talc, mannitol, sorbit, starch, sucrose ester. Examples thereof include solid diluents such as dextrin, sucrose, lactose, glucose, calcium carbonate and calcium phosphate, and liquid diluents such as water, physiological saline and ethanol.

〔Example〕

Experimental Example 1: 23 years old (female) When I was about 16 years old, I was quiet, and I was ridiculed by a classmate, so I dropped out of junior college and lived an empty life every day at home. At home, the futon of the kotatsu started to burn, but the fact that the futon was burning was not taken and the fire was not taken at all, so the family burned down. He was admitted to the hospital promptly, but his facial expression was poor, he had no illness or feeling of illness, and hardly responded to medical interviews. Then, when 3 tablets of the product of Example 2 were given after breakfast and 2 tablets after lunch, conversation became possible. After approving to go home, he was innocently pleased, and after returning to the hospital, he was happy to report what happened during his stay. In the blood
The amount of Zn was 94 μg / d before administration of the oyster meat extract, but today it has increased to 124 μg.

Experimental Example 2: 50 years old (female) Entered a certain music college in Tokyo and majored in the piano department and was recognized as an excellent student. As I practiced hard and practiced almost sleeplessly for consecutive nights before the graduation examination, the delusion of hallucinations began, and I quickly returned to work at home. The hallucinations and delusions disappeared with the internal use of chlorpromazine, etc., but on weekdays, other than practicing the piano,
It only deals with Shepherd dogs and does not do any housework. No emotional upset was observed when his father was ill. After that, the product of Example 2 is used after breakfast 3
I started to take 3 tablets after lunch, but one week later, my facial expression became soft, conversation became fluent, and I started to help with housework. Becoming active in practicing the piano,
Since my father was also sick, I said that I should take an apprentice and earn pocket money, and I am happy that I feel refreshed.

Experimental Example 3: 23 years old (female) She has been suffering from schizophrenia for several years and is being hospitalized in a hospital.
Although he was silent and lacked in facial expression, and was in a state of almost no use, he started taking 4 tablets of the product of Example 2 each morning,
Within a few days, my face became brighter and conversations increased, and I started to look after the old lady in my room. I returned home every Saturday and Sunday, but after taking the product of Example 1, I began to cook myself and enjoy ikebana.

Experimental Example 4: 30 years old (male) Since several years ago, others have been accusing me of monitoring my own behavior and making rumors about myself, so I used chlorpromazine etc. internally, but these symptoms disappeared. It was However, he is silent and lacks in facial expressions, and hardly speaks with others. Then, when the product of Example 2 was used internally with 3 tablets after breakfast and 3 tablets after lunch, the facial expression became brighter after a few days and conversations increased.

Experimental Example 5: 29 years old (female) I began to doubt that there was another mistress in the man who had an affectionate relationship, but in the voice of an old man in the neighborhood, "Be firm, he had a favorite person before. There was a hallucination such as "Noni", and he was troubled and suffered from insomnia.

Then, when three tablets of the product obtained in Example 5 were taken after breakfast, the hallucinations disappeared within a few days, the facial expression became bright and the response became clear, and the suspicions of the male partner became clear.

〔toxicity〕

Since the active ingredient of the zinc content enhancer in the brain of the present invention is a substance contained in oyster meat, it has extremely low toxicity and is extremely safe.

[Reference example]

Reference Example 1 An equal amount of distilled water is added to frozen oysters, and the mixture is subjected to heat extraction at 70 to 90 ° C. for 2 to 3 hours to perform solid-liquid separation. After the supernatant liquid after solid-liquid separation was concentrated to a solid content of 30 (w / w)%,
Spray drying to obtain the active ingredient of the present invention in powder form.

Reference Example 2 An equal amount of distilled water is added to frozen raw oysters, and the mixture is heated and extracted at 70 to 90 ° C. for 2 to 3 hours to perform solid-liquid separation. The supernatant liquid after solid-liquid separation is concentrated 5 to 6 times, and ethanol is added to the obtained concentrated liquid so that the final concentration becomes 75%. The ethanol added solution is allowed to stand for 2 to 4 days, and the obtained solution is separated into a precipitate and a supernatant. The precipitated portion is dried at 140 ° C. by a drum dryer and pulverized by a conventional method to obtain the active ingredient of the present invention.

Reference Example 3 Add 1 kg of distilled water to 1 kg of fresh oyster meat, and add 85
Extraction is carried out at ℃ for 2 hours to separate solid and liquid. Then, as a film, polysulfone type (NTR-351-P18L
By an industrial ultrafiltration method using P), 10 g of a fraction having a molecular weight of 100,000 or less was obtained. After that, washing with ethanol was repeated three times and then dried to obtain a white powdery crystalline zinc chelate compound. Its properties are as shown above.

Reference Example 4 To 1 kg of fresh oyster meat, 0.1% of a neutral protease originating from Aspergillus oryzae was added as an enzyme, and the enzyme action was performed at 40 to 45 ° C for 2 hours, and the enzyme action was stopped by heating to 85 ° C. After that, solid-liquid separation is performed. The supernatant after solid-liquid separation was concentrated to a solid content of 30% and spray-dried to obtain a powdery active ingredient of the present invention.

Reference Example 5 Reference Example 3 per 250 mg of the oyster meat extract obtained in Reference Example 2.
An oyster meat extract containing 20 mg of the zinc chelate compound obtained in step 1 was obtained.

〔Example〕

Example 1 1 kg of the active powder obtained in Reference Example 1 was mixed with 200 lactose.
g is added and mixed, and 15 to 20% of water is added to moisturize and knead. The kneaded product is granulated with a granulator, dried, and compressed into tablets. At this time, each tablet is prepared so that the active powder (oyster meat extract) is contained in an amount of 200 to 250 mg. After tableting, the active powder is syrup-coated into sugar-coated tablets as is conventional in order to prevent moisture and oxidation.

Example 2 Example 1 is replaced with the active powder obtained by the reference example 2 instead of the active powder obtained by the reference example 1.
A sugar-coated tablet is obtained in the same manner as.

Example 3 Example 1 is repeated except that the active powder obtained in Reference Example 3 is used in place of the active powder obtained in Reference Example 1.
A sugar-coated tablet is obtained in the same manner as.

Example 4 Example 1 is repeated except that the active powder obtained in Reference Example 4 is used instead of the active powder obtained in Reference Example 1.
A sugar-coated tablet is obtained in the same manner as.

Example 5 Example 1 is replaced with the active powder obtained by the reference example 5 instead of the active powder obtained by the reference example 1.
A sugar-coated tablet is obtained in the same manner as.

Claims (7)

[Claims] 1. A composition for treating schizophrenia, which comprises an oyster meat extract as an active ingredient. 2. The composition for treating schizophrenia according to claim 1, wherein the oyster meat extract is a hot water extract of oyster meat. 3. The treatment for schizophrenia according to claim 1, wherein the oyster meat extract is a precipitate obtained by subjecting an oyster meat hot water extract to alcohol fractionation. Composition. 4. A composition for treating schizophrenia, wherein the oyster meat extract is obtained by subjecting oyster meat to enzymatic decomposition. 5. An abundant amount of a passage fraction obtained by treating an oyster meat extract with a membrane that allows a substance having a molecular weight of 100,000 or less to pass therethrough. the 4th)
A composition for treating schizophrenia according to any one of items. 6. The oyster meat extract according to any one of claims (1) to (4), wherein the oyster meat extract is rich in a zinc chelate compound having the following characteristics. Composition for treating schizophrenia. The molecular weight measured by gel filtration analysis with Sephadex is 5,000 or less. Taurine and zinc as main constituents are positive for ninhydrin reaction, water-soluble, UV absorption: maximum absorption at 270-280 nm, 7. The composition for treating schizophrenia according to any one of claims (1) to (6), characterized in that the schizophrenia is a schizophrenia-type schizophrenia.