KR102107808B1 - Peptides for improving memory cognitive function - Google Patents

Abstract

The present invention relates to peptide for improving memory and a cognitive function. The peptide for improving memory and a cognitive function according to the present invention comprises an amino acid sequence represented by general formula 1a, a1-Gly-Gly-a1. In the general formula, a1 is Ala, Tyr, or Val. According to the present invention, the peptide exhibits an excellent improvement effect while administering a relatively small amount to brain and cognitive dysfunction through excellent initial improvement activity.

Description

Peptide for improving memory and cognitive function {PEPTIDES FOR IMPROVING MEMORY COGNITIVE FUNCTION}

The present invention relates to a peptide for improving memory and cognitive function. More specifically, it is intended to provide a peptide for improving cognitive function having an excellent initial effect on improving cognitive dysfunction and improving memory by using a peptide having a specific nucleotide sequence.

Dementia is a complex clinical syndrome that manifests a marked impairment in human cognitive function, intellectual ability, emotional and behavioral changes, and leads to daily and social life due to cerebral cortical dysfunction such as memory, attention, language function, and spatiotemporal ability. It is a state of great difficulty. When defined as dementia, it refers to a case in which one or more of the other cognitive functions, including memory, is impaired.

The causes of dementia are degenerative brain diseases such as Alzheimer's Disease or Parkinson's Disease, brain hemorrhage, metabolic diseases of hepatic encephalopathy, Wilson's Disease, infectious diseases of neurosyphilis, AIDS and alcohol There are various etiologies such as drug addiction and brain trauma, and in some forms, diseases that can cause structural and functional abnormalities in the central nervous system can cause dementia. Among them, dementia caused by Alzheimer's disease is the most prevalent with 50 to 60%, followed by dementia caused by cerebrovascular disease.

Memory cognitive impairment is the first symptom experienced by people with Alzheimer's and is also the most common. In the early stages of Alzheimer's disease, patients suffer from a recent memory impairment that is unable to memorize recent conversations or details of work, due to damage to the hippocampal neurons and reduced ability to store recent memories. . However, during this period, remote long-term memory of events in the distant past is relatively well maintained. However, as the disease progresses, the cerebral cortex associated with the storage of long-term memory is damaged, and these memories of the past gradually become impaired.

On the other hand, if the region where the brain artery is blocked and the tissue dies due to a blood clot following arteriosclerosis occurs in an important area such as the hippocampus, it develops as dementia. Or subcortical ischemic vascular dementia (SIVD) (which accounts for 35 to 67% of total vascular dementia) due to poor blood supply (Roman et al., Subcortical ischaemic vascular dementia.Lancet Neurol 2002; 1) : 426-436). Damage in subcortical ischemic vascular dementia (SIVD) mainly occurs in white matter and various methods are used to make animal models resembling these diseases (Hainsworth & Markus, Do in vivo experimental models reflect human cerebral small vessel disease? A systematic review J Cerebral Blood Flow & Metabolism 2008; 28: 1877-1891). For vascular dementia, it has been found that oligodendrocytes, which form white matter, die by apoptosis in conditions where vascular dementia occurs, and studies are underway to suppress and treat them.

Currently, in the case of Alzheimer's disease treatment in Korea, foreign companies rely heavily on imports, accounting for 98% of the market share. Moreover, one company occupies 80% of the market, so it can be said that it is actually monopolized (Korea Institute of Science and Technology Information, dementia treatment. P.116, 2002). This shows that the growth of dementia treatment field is urgent even in terms of national competitiveness. Therefore, the development of an effective anti-antagonist and memory-improving agent with fewer side effects can significantly improve the quality of life of Alzheimer's disease and improve and treat early symptoms, and also help patients with forgetfulness and dementia who suffer from memory cognitive impairment. Can give.

KR 10-2019-0018897 A KR 10-2018-0094556 A

An object of the present invention is to provide a peptide for improving memory and cognitive function.

The present invention is to provide a peptide for improving memory and cognitive function, which is composed of a specific nucleotide sequence, and has excellent initial improvement effect on memory and cognitive impairment.

It is an object of the present invention to provide a peptide for improving memory and cognitive function that can exhibit excellent improvement effect while administering relatively small amount to brain and cognitive dysfunction through excellent initial improvement activity.

Another object of the present invention is to provide a food, functional food or pharmaceutical product comprising the peptide for improving memory and cognitive function.

In order to achieve the above object, the peptide for improving memory and cognitive function according to an embodiment of the present invention may include an amino acid sequence represented by the following general formula 1a.

[Formula 1a]

a ₁ -Gly-Gly-a ₁

(In the above general formula, a ₁ is Ala, Tyr, or Val)

The peptide for improving memory and cognitive function according to another embodiment of the present invention may include an amino acid sequence represented by the following general formula 1b.

[General Formula 1b]

a ₁ -Gly-Gly-a ₁ -Gly-a ₂

(In the above general formula, a ₁ is Ala, Tyr, or Val, and a ₂ is Ala, Tyr, Ile or Val.)

Food according to another embodiment of the present invention may be to include the peptide or the peptide composition.

A drug for preventing or improving cognitive dysfunction according to another embodiment of the present invention may include the peptide or the peptide composition.

The cognitive dysfunction is dementia, learning disability, real certification, forgetfulness, aphasia, agonism, delirium, AIDS-induced dementia, Vincewaner's disease, Lewy body dementia, frontotemporal dementia, mild cognitive impairment, multiple infarct dementia, pick disease, meaning It may be selected from the group consisting of dementia, Alzheimer's dementia or vascular dementia.

Hereinafter, the present invention will be described in more detail.

The peptide for improving memory and cognitive function according to an embodiment of the present invention may include an amino acid sequence represented by the following general formula 1a.

[Formula 1a]

a ₁ -Gly-Gly-a ₁

(In the above general formula, a ₁ is Ala, Tyr, or Val)

The peptide for improving memory and cognitive function according to another embodiment of the present invention may include an amino acid sequence represented by the following general formula 1b.

[General Formula 1b]

a ₁ -Gly-Gly-a ₁ -Gly-a ₂

(In the above general formula, a ₁ is Ala, Tyr, or Val, and a ₂ is Ala, Tyr, Ile or Val.)

When hydrolyzing silk fibroin by combining specific proteolytic enzymes, when amino acids having a specific sequence are included, not only the cognitive function and memory improvement effect are exhibited, but also the cognitive function and memory improvement effect are exhibited within a very short period. , Unlike the general hydrolyzate, a specific analysis was performed to confirm the amino acid sequence showing a fast action and effect.

The peptide for improving memory and cognitive function prepared in another experimental step of the present invention includes an amino acid sequence represented by the following general formula 1a or general formula 1b.

[Formula 1a]

a ₁ -Gly-Gly-a ₁

(In the above general formula, a ₁ is Ala, Tyr, or Val)

[Formula 1b]

a ₁ -Gly-Gly-a ₁ -Gly-a ₂

(In the above general formula, a ₁ is Ala, Tyr, or Val, and a ₂ is Ala, Tyr, Ile or Val.)

When hydrolyzing silk fibroin by combining specific proteolytic enzymes, when amino acids having a specific sequence are included, not only the cognitive function and memory improvement effect are exhibited, but also the cognitive function and memory improvement effect are exhibited within a very short period. , Unlike the general hydrolyzate, a specific analysis was performed to confirm the amino acid sequence showing a fast action and effect.

Accordingly, a peptide comprising the amino acid sequence of the general formula 1a or general formula 1b to analyze the corresponding hydrolyzate so that the above effects can be exhibited; It is estimated that the above-described effect is exhibited by a peptide or a peptide composition composed of a peptide composition in which a peptide comprising the amino acid sequence of Formula 1a or Formula 1b and a peptide comprising the amino acid sequence of Formula 2 are mixed, As a result of conducting experiments on this, it was confirmed that the peptide or the peptide composition showed a high degree of cognitive function and memory improvement effect as well as a cognitive function and memory improvement effect within a very short period of time.

Preferably, the peptide comprising the amino acid sequence of Formula 1a may be any one of Pa-1 to Pa-3 as shown in [Table 1] below. In addition, the peptide comprising the amino acid sequence of Formula 1b may be any one of Pb-1 to Pb-4 as shown in [Table 1] below.

Peptide Amino acid sequence Pa-1 Ala-Gly-Gly-Ala Pa-2 Tyr-Gly-Gly-Tyr Pa-3 Val-Gly-Gly-Val Pb-1 Tyr-Gly-Gly-Tyr-Gly-Ile Pb-2 Tyr-Gly-Gly-Tyr-Gly-Val Pb-3 Tyr-Gly-Gly-Tyr-Gly-Ala Pb-4 Tyr-Gly-Gly-Tyr-Gly-Tyr

More preferably, the peptide of Formula 1a may be peptides Pa-2 and Pa-3 in [Table 2]. In the case of the peptide, the cognitive function and memory improvement effect are excellent, and the initial effect is very excellent, thereby improving the cognitive function and memory improvement in a short period of time.

Particularly, in the case of the peptide Pa-2, not only is the cognitive function and the improvement effect excellent, but also can exhibit the excellent cognitive function improvement effect in a shorter time.

More preferably, the peptide of Formula 1b may be a peptide Pb-1 or Pb-4 in [Table 2].

According to the above range, the effect of improving cognitive function and memory can be excellent, and the effect of improvement can be rapidly increased in the initial stage of administration.

Preferably, the peptide composition according to another embodiment of the present invention includes a peptide comprising an amino acid sequence represented by the following general formula 1a, and further comprises a peptide comprising an amino acid sequence represented by the following general formula 2 May be

In addition, the peptide composition according to the present invention may include a peptide comprising an amino acid sequence represented by the following general formula 1b, and may further include a peptide comprising an amino acid sequence represented by the following general formula 2.

[Formula 2]

Ile-Gly-Z ₁ -Z ₂

(In the above general formula, Z ₁ is Ala, Tyr, Val or Gln, and Z ₂ is Ala, Tyr, Val or Gly.)

Preferably, the peptide represented by [General Formula 2] may be any one of P2-1 to P2-4 as shown in [Table 2].

Peptide Amino acid sequence P2-1 Ile-Gly-Tyr-Val P2-2 Ile-Gly-Val-Ala P2-3 Ile-Gly-Ala-Tyr P2-4 Ile-Gly-Gln-Gly

When the peptides according to [Table 2] are mixed to form a peptide composition, the effect of improving cognitive function and memory can be excellent, and the effect can be exhibited within a short period of time.

Meanwhile, in the peptide composition, the peptide includes a peptide represented by [General Formula 1a], and a peptide represented by [General Formula 2] is 30 to 80 relative to 100 parts by weight of the peptide represented by [General Formula 1a]. It may be included in parts by weight.

Preferably, the peptide composition includes a peptide represented by [General Formula 1b], and a peptide represented by [General Formula 2] with respect to 100 parts by weight of the peptide represented by [General Formula 1b] is 30 to 80 It may be included in parts by weight.

In the case of the above range, the activity of the cognitive function and the improvement effect can be quickly displayed due to the synergistic effect by interaction.

Food according to another embodiment of the present invention may be to include the peptide or the peptide composition.

A drug for preventing or improving cognitive dysfunction according to another embodiment of the present invention may include the peptide or the peptide composition.

The cognitive dysfunction is dementia, learning disability, real certification, forgetfulness, aphasia, agonism, delirium, AIDS-induced dementia, Vincewaner's disease, Lewy body dementia, frontotemporal dementia, mild cognitive impairment, multiple infarct dementia, pick disease, meaning It may be selected from the group consisting of dementia, Alzheimer's dementia or vascular dementia.

The composition may include a pharmaceutically acceptable carrier. The pharmaceutically acceptable carrier contained in the composition is commonly used in the formulation, lactose, dextrose, sucrose, sorbitol, mannitol, starch, acacia rubber, calcium phosphate, alginate, gelatin, calcium silicate, fine Crystalline cellulose, polyvinylpyrrolidone, cellulose, water, syrup, oils, and the like, but is not limited thereto. The pharmaceutical composition may further include a lubricant, a wetting agent, a sweetener, a flavoring agent, an emulsifying agent, a suspending agent, a preservative, etc. in addition to the above components.

The pharmaceutical composition can be administered orally or parenterally.

When administered orally, proteins or peptides are digested, so oral compositions must be formulated to coat the active agent or to protect it from degradation in the stomach. In addition, the composition may be administered by any device capable of transporting the active substance to target cells.

A suitable dosage of the pharmaceutical composition may be used in a pharmaceutically effective amount, which means an amount sufficient to prevent or treat memory, cognitive or learning disorders.

The present invention provides a peptide for improving memory and cognitive function.

The present invention provides a peptide for improving memory and cognitive function, which is composed of a specific base sequence and has excellent initial improvement effect on memory and cognitive impairment.

The present invention provides a peptide for improving memory and cognitive function that can exhibit excellent improvement effect while administering relatively small amount to brain and cognitive dysfunction through excellent initial improvement activity.

The present invention provides a food, functional food or medicine containing the peptide for improving memory and cognitive function.

1 relates to an experiment for improving the cognitive memory effect of a peptide according to an embodiment of the present invention.
Figure 2 relates to an experiment for improving the cognitive memory effect of the peptide according to an embodiment of the present invention.
3 relates to an experiment for improving the cognitive memory effect of a peptide according to an embodiment of the present invention.
4 relates to an experiment for improving the cognitive memory effect of a peptide according to an embodiment of the present invention.

Hereinafter, embodiments of the present invention will be described in detail so that those skilled in the art to which the present invention pertains can easily practice. However, the present invention can be implemented in many different forms and is not limited to the embodiments described herein.

[Production Example 1: Synthesis and mixing of peptides]

Among the silk fibroin hydrolysates, the hydrolysates showing the effect of improving cognitive function and memory within a short period of time were analyzed, and a peptide capable of exhibiting a fast effect was predicted.

Accordingly, the peptides of Pa-1 to Pa-3 and Pb-1 to Pb-4 were synthesized by requesting external peptides to confirm whether the predicted peptides exhibited cognitive and memory improvement effects within a short period of time.

In addition, in order to confirm the synergistic effect by mixing of each peptide, P2-1 to P2-4 of [Table 2] were synthesized, and synthetic peptides were mixed with the composition shown in [Table 3] to prepare a peptide composition. .

Pb-1 M1 M2 M3 M4 Pb-1 100 100 100 100 100 P2-1 - 50 - - - P2-2 - - 50 - - P3-3 - - 50 - P4-4 - - - - 50

(Unit: parts by weight)

[Experimental Example 1: Experiment on the effect of improving memory and cognitive function]

Experimental Example 1: Animal model experiment for improving cognitive function

A. Preparation of experimental animals

The experimental animals are male white paper (Sprague Dawley, 140-180 g, Korea Laboratory Animal Center), and they are put in 4 animals per breeding box for a week in a constant environment (room temperature 25 ± 1 ℃, relative humidity 60 ± 10%). Water was provided without restriction, and at this time, limited feeding was performed to maintain 80% of the weight. A total of 50 animals were used in this experiment. From 3 days before training, the test was conducted by adapting to the maze for 5 minutes.

B. delayed alternation test

There are a total of three passages (left, right, and center), and each passage entrance has a 'ㅠ' shaped labyrinth with partitions installed so that the experimenter can control the entry and exit of animals.

In the first trial, the starting box was adapted for 1 minute. The first trial was a 'forced selection trial', where one passage was blocked with a partition and the back was blocked with a partition when an animal entered the other passage. Animals were considered to have entered when the limbs of the animals had passed through the entrance to the passage. Animals were fed for 60 seconds in the passage.

From the next trial, the 'free selection trial' allowed the animals to freely select the direction of the passage (left or right) starting from the starting box. Animals were compensated for prey only when they entered the passage from the previous trial and into the other.

The interval between trials was 5 seconds and 20 seconds with a delay, and the cut-off time for each trial was 60 seconds. The number of times the animal entered the passage through which the reinforcement was given and the time taken to enter the passage were measured. The same procedure was performed for 9 days of 10 trials a day to evaluate.

C. Method of administration

Synthesized and mixed P1-1 to P1-6 and M1 to M4 according to the preparation example of the present invention were prepared as a silk peptide solution using physiological saline and administered intraperitoneally into mice. As a control, physiological saline was used.

D. Results of cognitive memory evaluation

The results of the T-maze experiment for the groups administered with P1-1 to P1-6 and M1 to M4 are shown in [Fig. 1] and [Fig. 3] below. [Fig. 1] and [Fig. 3], the experiment was conducted by configuring the trial interval as 5 seconds, and the performance gradually improved during the training period of 9 days.

Referring to FIG. 1, it can be seen that in the case of Pa-1 to Pa-3 disclosed in the present invention, overall cognitive memory is improved. In addition, the peptide Pa-2 has a higher cognitive function and memory improvement effect compared to other examples Pa-1 and P1-3. Particularly, it was confirmed that in the case of Pa-1, the effect of improving cognitive function and memory increased rapidly from the beginning of administration compared to other synthetic peptides.

In addition, it was confirmed that Pb1 to Pb4 exhibit superior cognitive and memory improvement effects than Pa-1 and Pa-3. Particularly, it was confirmed that Pb1 not only has a superior cognitive function and memory improvement effect more clearly than Pa2, but also has excellent initial improvement activity.

Referring to FIG. 3, it can be seen that when M1 to M4 disclosed in the present invention are additionally mixed and used, not only synergism due to interaction occurs, but the initial improvement effect is rapidly improved. That is, referring to FIG. 2, P2-2 is relatively superior in cognitive function and memory improvement effect, but P2-1, P2-3 and P2-4, except for this, have the effect of improving cognitive function and memory in itself. The degree of improvement is relatively low. However, when the entire P2-1 to P2-4 are mixed with a peptide represented by [General Formula 1a] or [General Formula 1b] and provided as a peptide composition, the effect of synergy and memory improvement by synergistic effect due to interaction and initial It can be seen that the improvement effect is greatly increased.

Therefore, when the peptide represented by [General Formula 1a] or [General Formula 1b] and the peptide represented by [General Formula 2] are mixed to form a peptide composition, the effect of improving cognitive memory may be increased, and a composition having a fast initial activity may be used. We can confirm that we can provide.

In particular, in the case of a food or drug for improving cognitive function and memory, initial activity is very important, and according to the present invention, it is possible to provide a food or drug with improved effect for improving cognitive function and memory and initial improvement.

Although the preferred embodiments of the present invention have been described in detail above, the scope of the present invention is not limited thereto, and various modifications and improvements of those skilled in the art using the basic concept of the present invention defined in the following claims are also provided. It belongs to the scope of rights.

<110> NATURESENSE <120> PEPTIDES FOR IMPROVING MEMORY COGNITIVE FUNCTION <130> WP193118 <160> 11 <170> KoPatentIn 3.0 <210> 1 <211> 4 <212> PRT <213> Artificial Sequence <220> <223> Pa-1 <400> 1 Ala Gly Gly Ala   One <210> 2 <211> 4 <212> PRT <213> Artificial Sequence <220> <223> Pa-2 <400> 2 Tyr Gly Gly Tyr   One <210> 3 <211> 4 <212> PRT <213> Artificial Sequence <220> <223> Pa-3 <400> 3 Val Gly Gly Val   One <210> 4 <211> 6 <212> PRT <213> Artificial Sequence <220> <223> Pb-1 <400> 4 Tyr Gly Gly Tyr Gly Ile   1 5 <210> 5 <211> 6 <212> PRT <213> Artificial Sequence <220> <223> Pb-2 <400> 5 Tyr Gly Gly Tyr Gly Val   1 5 <210> 6 <211> 6 <212> PRT <213> Artificial Sequence <220> <223> Pb-3 <400> 6 Tyr Gly Gly Tyr Gly Ala   1 5 <210> 7 <211> 6 <212> PRT <213> Artificial Sequence <220> <223> Pb-4 <400> 7 Tyr Gly Gly Tyr Gly Tyr   1 5 <210> 8 <211> 4 <212> PRT <213> Artificial Sequence <220> <223> P2-1 <400> 8 Ile Gly Tyr Gly   One <210> 9 <211> 4 <212> PRT <213> Artificial Sequence <220> <223> P2-2 <400> 9 Ile Gly Val Ala   One <210> 10 <211> 4 <212> PRT <213> Artificial Sequence <220> <223> P2-3 <400> 10 Ile Gly Ala Tyr   One <210> 11 <211> 4 <212> PRT <213> Artificial Sequence <220> <223> P2-4 <400> 11 Ile Gly Gln Gly   One

Claims (5)

A peptide represented by any one of SEQ ID NOs: 4 to 7. delete Food for improving memory and cognitive function comprising the peptide according to claim 1. A drug for preventing or improving cognitive dysfunction comprising the peptide according to claim 1. According to claim 4,
The cognitive dysfunction is dementia, learning disability, real certification, forgetfulness, aphasia, aphasia, delirium, AIDS-induced dementia, Vincewaner's disease, Lewy body dementia, frontotemporal dementia, mild cognitive impairment, multiple infarct dementia, pick disease, meaning Is selected from the group consisting of dementia, Alzheimer's dementia or vascular dementia
medicine.

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