JPWO2020054090A1 - Sugar and / or lipid metabolism improver - Google Patents

Abstract

Primarily to provide sugar and / or lipid metabolism improvers.
A β1,3-glucan derivative in which at least one hydroxy group of at least some glucose residues is -NR ¹ R ² (R ¹ and R ² are independent hydrogen atoms or carbon atoms at each appearance. An agent for improving the metabolism of sugars and / or lipids, which comprises a β1,3-glucan derivative substituted with (showing an alkyl group of numbers 1 to 6).

Description

The present invention mainly relates to a sugar and / or lipid metabolism improving agent.

In recent years, due to changes in eating habits, metabolic syndrome caused by the accumulation of visceral fat has increased. Metabolic syndrome causes obesity, visceral fat syndrome, impaired glucose tolerance, hypertension, etc., and it is known that diabetes leads to ophthalmopathy, neuropathy, nephropathy, etc. through angiopathy. Therefore, there is a need for a means for preventing obesity and the accumulation of visceral fat, which are the roots of this pathological condition, for example, an effective means for improving lipid metabolism and glucose metabolism.

On the other hand, at present, drugs for improving lipid metabolism and glucose metabolism are known as diabetes therapeutic agents, obesity improving agents and the like. However, since many of these are synthetic small molecule compounds, natural ingredients are desirable from the viewpoint of constant ingestion. From the viewpoint of more radical prevention of lifestyle-related diseases, it is desirable to be able to improve obesity, visceral fat accumulation, and both lipid metabolism and glucose metabolism.

Bacterial infectious diseases, on the other hand, are a serious cause of death for living organisms. For this reason, antibacterial agents are used in a wide variety of fields such as the medical field. The development of new antibacterial agents is constantly being sought, but the speed at which bacterial resistance is acquired is surpassing the speed at which antibiotics are developed, and it is said that bacterial infections can become a fatal disease in the future. From this point of view, a substance having antibacterial activity for which resistance is not acquired is useful. In addition, suppressing the growth of bacteria in the environment and preventing the spread of infectious diseases will play an even more important role than ever before. As another example of the use of antibacterial substances, the components and instruments that many people can come into contact with (eg in public facilities and hospitals) are antibacterial to prevent the transmission and spread of bacterial infections through them. desirable.

Wounds are susceptible to bacterial infections due to the lack of skin that acts as a barrier to bacteria. In addition, when wound infection is caused by some bacterial infections, it may become serious and wound healing may be delayed. Therefore, in wound treatment, basically moist treatment and wound healing action are performed. A component having an antibacterial action may be used together with a component having an antibacterial action. Although silver ions are widely used for this purpose, there is some disagreement about their effects, and a locally usable substance having stable antibacterial activity is required.

Paramylon is a β-1,3-glucan produced by Euglena. In recent years, it has been reported that paramylon is useful for wound treatment and allergy suppression (Patent Documents 1 and 2).

Japanese Patent Application Laid-Open No. 2011-184371 Japanese Patent Application Laid-Open No. 2014-231479

An object of the present invention is to provide an agent for improving metabolism of sugar and / or lipid. Preferably, it is an object of the present invention to provide an agent for improving metabolism of both sugars and lipids.

In another embodiment of the present invention, it is an object of the present invention to provide an antibacterial agent as a new active ingredient.

As a result of diligent research in view of the above problems, the present inventor is a β1,3-glucan derivative in which at least one hydroxy group of at least a part of glucose residues is replaced with ^{−NR 1} R ^2. , 3-Glucan derivatives have been found to exert an action of improving the metabolism of sugars and / or lipids. The present inventor has completed the present invention as a result of further research based on this finding.

That is, the present invention includes the following aspects.

Item 1. A β1,3-glucan derivative in which at least one hydroxy group of at least some glucose residues is -NR ¹ R ² (R ¹ and R ² are independent hydrogen atoms or carbon atoms at each appearance. An agent for improving the metabolism of sugars and / or lipids, which comprises a β1,3-glucan derivative substituted with (showing an alkyl group of numbers 1 to 6).

Item 2. Item 2. The metabolism improving agent according to Item 1, wherein the hydroxy group is the 6-position hydroxy group.

Item 3. Item 2. The metabolism improving agent according to Item 1 or 2, wherein R ¹ and R ^{2 are hydrogen atoms.}

Item 4. Item 2. The metabolism improving agent according to any one of Items 1 to 3, wherein the β1,3-glucan derivative is a paramylon derivative or a curdlan derivative.

Item 5. Item 4. The metabolism improving agent according to any one of Items 1 to 4, wherein the β1,3-glucan derivative is linear and all the bonds between sugar residues are β1,3-glucoside bonds.

Item 6. Item 2. The metabolism improving agent according to any one of Items 1 to 5, which is used for improving both glucose metabolism and lipid metabolism.

Item 7. Item 2. The metabolism improving agent according to any one of Items 1 to 6, which is a pharmaceutical.

Item 8. Item 2. The metabolism improving agent according to any one of Items 1 to 7, which is used for prevention or amelioration of at least one selected from the group consisting of (1) metabolic syndrome or (2) obesity, diabetes, and dyslipidemia.

Item 9. For use as a sugar and / or lipid metabolism improver,
A β1,3-glucan derivative in which at least one hydroxy group of at least some glucose residues is -NR ¹ R ² (R ¹ and R ² are independent hydrogen or carbon atoms at each appearance. A β1,3-glucan derivative obtained by substituting an alkyl group of numbers 1 to 6).

Item 10. A β1,3-glucan derivative in which at least one hydroxy group of at least some glucose residues is -NR ¹ R ² (R ¹ and R ² are independent hydrogen or carbon atoms at each appearance. A method for improving glucose and / or lipid metabolism, which comprises applying a β1,3-glucan derivative substituted with (1 to 6) an alkyl group to the subject.

Item 11. For producing sugar and / or lipid metabolism improvers,
A β1,3-glucan derivative in which at least one hydroxy group of at least some glucose residues is -NR ¹ R ² (R ¹ and R ² are independent hydrogen or carbon atoms at each appearance. Use of β1,3-glucan derivative which is replaced by (indicating an alkyl group of numbers 1 to 6).

In addition, as a result of diligent research in view of the above problems, the present inventors have replaced at least one hydroxy group of at least a part of glucose residues in the β1,3-glucan derivative with -NR ¹ R ^2. It was found that the β1,3-glucan derivative obtained has antibacterial activity. The present inventors have completed the present invention as a result of further research based on such findings.

That is, the present invention includes the following aspects.

Item A. A β1,3-glucan derivative in which at least one hydroxy group of at least some glucose residues is -NR ¹ R ² (R ¹ and R ² are independent hydrogen or carbon atoms at each appearance. An antibacterial agent containing a β1,3-glucan derivative substituted with (showing an alkyl group of numbers 1 to 6).

Item B. Item 2. The antibacterial agent according to Item A, wherein the hydroxy group is a 6-position hydroxy group.

Item C. Item 2. The antibacterial agent according to Item A or B, wherein R ¹ and R ^{2 are hydrogen atoms.}

Item D. Item 4. The antibacterial agent according to any one of Items A to C, wherein the β1,3-glucan derivative is a paramylon derivative or a curdlan derivative.

Item E. Item 4. The antibacterial agent according to any one of Items A to D, wherein the β1,3-glucan derivative is linear and all the bonds between sugar residues are β1,3-glucoside bonds.

Item F. A wound healing agent comprising the antibacterial agent according to any one of items A to E.

Item G. An antibacterial material containing the antibacterial agent according to any one of Items A to E.

Item H. For use as an antibacterial agent, wound healing agent, or antibacterial material,
A β1,3-glucan derivative in which at least one hydroxy group of at least some glucose residues is -NR ¹ R ² (R ¹ and R ² are independent hydrogen or carbon atoms at each appearance. A β1,3-glucan derivative obtained by substituting an alkyl group of numbers 1 to 6).

Item I. A β1,3-glucan derivative in which at least one hydroxy group of at least some glucose residues is -NR ¹ R ² (R ¹ and R ² are independent hydrogen or carbon atoms at each appearance. An antibacterial method, a wound healing method, or a method for imparting antibacterial performance to a material, which comprises applying a β1,3-glucan derivative substituted with an alkyl group of No. 1 to 6) to the subject.

Item J. For the manufacture of antibacterial agents, wound healing agents, or antibacterial materials,
A β1,3-glucan derivative in which at least one hydroxy group of at least some glucose residues is -NR ¹ R ² (R ¹ and R ² are independent hydrogen or carbon atoms at each appearance. Use of β1,3-glucan derivative which is replaced by (indicating an alkyl group of numbers 1 to 6).

According to the present invention, an agent for improving metabolism of sugar and / or lipid can be provided. According to the metabolism improving agent of the present invention, it is also possible to improve the metabolism of both sugar and lipid. Furthermore, according to the metabolism improving agent of the present invention, it is possible to prevent or improve obesity, visceral fat syndrome, metabolic syndrome, diabetes, dyslipidemia and the like.

Further, according to the present invention, it is possible to provide an antibacterial agent having a new active ingredient. According to the antibacterial agent of the present invention, a strong antibacterial action (particularly a bactericidal action) can be exerted against various types of bacteria. Further, according to the present invention, it is possible to provide a wound healing agent, an antibacterial material, etc. using the antibacterial agent of the present invention.

The IR data of the compound obtained in Synthesis Example 1-2 is shown. The carbon NMR data of the compound obtained in Synthesis Example 1-2 is shown. The IR data of the compound obtained in Synthesis Example 1-3 is shown. The carbon NMR data of the compound obtained in Synthesis Example 1-3 is shown. The transition of the body weight (average value) during the test breeding period in Test Example 1 is shown. The transition of the body weight (average) during the test breeding period in Test Example 2 is shown. The HE-stained image of the liver in Test Example 3 is shown. The bar in the figure indicates 100 μm. The measurement results of the liver weight and the white adipose tissue weight in Test Example 3 are shown. The stained image of the triglyceride in feces using the Zudan IV stained powder in Test Example 3 is shown. The measurement result of the expression level of the bile acid synthesis-related gene in Test Example 3 is shown. The measurement result of the bile acid composition in 1 gram of feces in Test Example 3 is shown. The HE-stained images of the stomach, ileum, colon, and rectum in Test Example 3 are shown.

In the present specification, the expressions "contains" and "contains" include the concepts of "contains", "contains", "substantially consists" and "consists of only". Further, in the present specification, "antibacterial" is a concept including both "bactericidal" and "bacteriostatic".

In one aspect of the present invention, the β1,3-glucan derivative is a β1,3-glucan derivative in which at least one hydroxy group of at least a part of glucose residues is replaced with ^{−NR 1} R ^2. In the present specification, a sugar and / or lipid metabolism improving agent containing "β1,3-glucan derivative of the present invention" (in the present specification, "the metabolism improving agent of the present invention"). May be shown).

Further, in one aspect of the present invention, β1,3-glucan is a β1,3-glucan derivative in which at least one hydroxy group of at least a part of glucose residues is replaced with ^{−NR 1} R ^2. Regarding antibacterial agents (sometimes referred to as "antibacterial agents of the present invention" in the present invention) containing derivatives (sometimes referred to as "β1,3-glucan derivatives of the present invention" in the present specification). .. This will be described below.

These will be described below.

1. 1. β1,3-Glucan Derivative The β1,3-glucan derivative of the present invention is a β1,3-glucan derivative in which at least one hydroxy group of at least a part of glucose residues is replaced with ^{−NR 1} R ^2.

The "β1,3-glucan" is not particularly limited as long as it has one sugar chain (or sugar chain structure) in which glucose is linked only by β1,3 bonds as a main chain. The β1,3-glucan may be obtained by chemical synthesis, but from the viewpoint of availability and the like, natural β1,3-glucan produced by various organisms is preferable. Examples of natural β1,3-glucan include paramylon, curdlan, laminarin, callose, lentinan, schizophyllan and the like.

The "glucose residue" is not particularly limited as long as it is a glucose residue constituting β1,3-glucan, for example, in a single linear sugar chain in which glucose is linked only by β1,3 bonds. Glucose residues are the formulas (a) to (c):

It is a monovalent or divalent group represented by.

"At least a part of glucose residues" means a part or all of glucose residues constituting β1,3-glucan.

The "at least one hydroxy group of the glucose residue" is not particularly limited as long as it is at least one of the hydroxy groups present in the structure of the glucose residue (usually a plurality of). For example, in the formula (a), at least one hydroxy group of the glucose residue is selected from the group consisting of the hydroxy group represented by * 1, the hydroxy group represented by * 2, and the hydroxy group represented by * 3. Means at least one species. From the viewpoint that the hydroxy group can more reliably exert the metabolism improving activity of sugar and / or lipid (for example, at a lower concentration, etc.), the hydroxy group at the 6-position (in the case of the formula (a), * It is preferable that the hydroxy group represented by 1) is contained, and it is preferable that only the hydroxy group at the 6-position (that is, no hydroxy group other than the hydroxy group at the 6-position is contained) is contained.

R ¹ and R ² each independently represent a hydrogen atom or an alkyl group having 1 to 6 carbon atoms at each appearance. "Independently in each appearance" means that R ¹ and R ² are independent (same or different), and when there are multiple ^{-NR 1} R ^{2 , each R 1} and each R ² includes both meanings independently (same or different). The meaning of the term is the same as described later.

The "alkyl groups having 1 to 6 carbon atoms" represented by ^{R 1} and R ^{2 include both linear and branched chains.} The alkyl group preferably has 1 to 4, more preferably 1 to 2, and even more preferably 1. Specific examples of the alkyl group include methyl group, ethyl group, n-propyl group, isopropyl group, n-butyl group, isobutyl group, tert-butyl group, sec-butyl group, n-pentyl group, neopentyl group, n. -Hexyl group, 3-methylpentyl group and the like can be mentioned.

From the viewpoint that the metabolism-improving activity of sugars and / or lipids can be exhibited more reliably (for example, at a lower concentration, etc.), preferably at least one ^{of R 1} and R ^{2 (R 1} or R ² , or R ¹ and R). ² ) is a hydrogen atom, more preferably ^{both R 1} and R ² are hydrogen atoms.

"At least one hydroxy group of ^{a glucose residue is replaced by -NR 1} R ^{2 ", in other words, -NR 1} R ² is present in place of at least one hydroxy group of a glucose residue. Is to become. For example, in formula (a), if only the hydroxy group at position 6 of the glucose residue ^{is replaced by −NR 1} R ² , then the glucose residue is in formula (a'):

Can be represented by.

The β1,3-glucan derivative of the present invention is a single sugar chain in which glucose and / or a glucose derivative in which at least one hydroxy group is ^{replaced with −NR 1} R ^{2 is linked only by a β1,3 bond (} Alternatively, it is not particularly limited as long as it has a sugar chain structure as a main chain, and is not limited to a linear one, and includes one having a branched chain.

In the linear case, when all the bonds between sugar residues are β1,3-glucosidic bonds (that is, the β1,3-glucan derivative of the present invention has glucose and / or at least one hydroxy group of -NR ^1). When the ^{glucose derivative replaced by R 2} consists of only one sugar chain linked by only β1,3 bonds), and sugars at the end of the sugar chains and other binding modes (for example, β1,4 bonds) The case where the end of the chain is connected is included.

The branched chain is not particularly limited, for example, the hydroxy group at the 6-position of the glucose derivative residue in which ^{the glucose residue on the main chain or at least one hydroxy group is replaced with −NR 1} R ^{2, and other sugars.} There is a branch chain in which the hydroxy group of the above is glycosidic bonded and extends from the glycosidic bond.

The β1,3-glucan derivative of the present invention is preferably linear without side chains from the viewpoint that it has no effect on metabolism and uniform molecules are easily formed by the introduction of side chains. From the viewpoint that the metabolism-improving activity of sugars and / or lipids can be exhibited more reliably (for example, at a lower concentration, etc.), it is preferably linear, more preferably linear, and between sugar residues. All bonds are β1,3-glucoside bonds.

From the same point of view, in the β1,3-glucan derivative of the present invention, the main chain (glucose and / or the glucose derivative in which at least one hydroxy group is ^{replaced with −NR 1} R ² is only β1,3 bond. The number of sugar residues constituting one linked sugar chain (or sugar chain structure) is 100% of the total number of sugar residues constituting the entire β1,3-glucan derivative of the present invention. For example, it is 70% or more, preferably 80% or more, more preferably 90% or more, further preferably 95% or more, still more preferably 97% or more, and particularly preferably 99% or more.

The weight average molecular weight of the β1,3-glucan derivative of the present invention is not particularly limited, but from the viewpoint that the metabolism-improving activity of sugars and / or lipids can be exhibited more reliably (for example, at a lower concentration, etc.), for example, 1 × 10 ^{4 to} 2 × 10 ⁶ , preferably 5 × 10 ⁴ to 1 × 10 ⁶ , and more preferably 1 × 10 ⁵ to 1 × 10 ⁶ .

The weight average molecular weight is β1,3- of the present invention from the viewpoint that the metabolism improving activity of sugars and / or lipids, which can be measured by the GPC method, can be more reliably exerted (for example, at a lower concentration). In the glucan derivative, ^{the number of glucose derivative residues having −NR 1} R ² is, for example, 5% or more, preferably 5% or more, based on 100% of the total number of sugar residues constituting the entire β1,3-glucan derivative of the present invention. It is 10% or more, more preferably 20% or more, still more preferably 40% or more, still more preferably 60% or more, still more preferably 80% or more, and particularly preferably 90% or more.

In the β1,3-glucan derivative of the present invention, a part of the hydroxy group of the constituent sugar residue may be replaced with a group other than ^{−NR 1} R ^2.

As a preferable aspect of the β1,3-glucan derivative of the present invention, for example, the general formula (1):

[In the formula, R ³ and R ⁴ each independently indicate a hydroxy group or −NR ¹ R ² (where R ¹ and R ² are the same as above) (provided that all R ³ and all R 3 and all). Unless R ⁴ is a hydroxy group at the same time). n indicates an integer from 25 to 25000. ]
Β1,3-glucan derivatives having a structure represented by (2) as a main chain can be mentioned, and the general formula (2): is preferable.

[In the equation, R ³ , R ⁴ , and n are the same as described above. ]
Examples thereof include β1,3-glucan derivatives represented by.

n is preferably 50 to 5000, more preferably 100 to 2000, and even more preferably 200 to 1000, from the viewpoint that the metabolism improving activity of sugar and / or lipid can be exhibited more reliably (for example, at a lower concentration, etc.). Is.

R ⁴ is preferably a hydroxy group from the viewpoint that it can more reliably exert the metabolism improving activity of sugars and / or lipids (for example, at a lower concentration).

The β1,3-glucan derivative of the present invention also includes the form of a salt. The salt is not particularly limited as long as it is a pharmaceutically acceptable salt. The salt is not particularly limited, and examples thereof include an acidic salt with ^{−NR 1} R ^2. Examples of acidic salts are inorganic acid salts such as hydrochloride, hydrobromide, sulfate, nitrate, phosphate; acetate, propionate, tartrate, fumarate, maleate, malic acid. Examples thereof include organic acid salts such as salts, citrates, methane sulfonates and paratoluene sulfonates.

The β1,3-glucan derivative of the present invention also includes the form of a solvate. Examples of the solvent include water, a pharmaceutically acceptable organic solvent (for example, ethanol, glycerol, acetic acid, etc.) and the like.

2. Method for Producing β1,3-Glucan Derivative The β1,3-glucan derivative of the present invention can be synthesized by various methods. For example, it can be synthesized according to the method described in publicly known documents such as Carbohydrate Polymer 122 (2015) 84-92. And Japanese Patent Application Laid-Open No. 2012-180328. As an example, for a β1,3-glucan derivative in which the hydroxy group at the 6-position of at least a part of glucose residues is replaced with an amino group, using β1,3-glucan as a starting material, for example, the following reaction formula:

[In the formula, X represents a halogen atom. Partial structure A shows the glucose residue in the starting material β1,3-glucan. Partial structures B to D indicate glucose derivative residues in β1,3-glucan derivatives. ]
Can be synthesized according to. Further, the β1,3-glucan derivative of the present invention having another structure can also be synthesized by a method according to the above formula, a method in which a known reaction is combined with the above formula, or the like.

(2-1) Starting material (β1,3-glucan having partial structure A) → β1,3-glucan derivative having partial structure B In this step, the starting material (β1,3-glucan having partial structure A) and By reacting with a halogenating agent, a β1,3-glucan derivative having a partial structure B can be obtained.

The halogenating agent is not particularly limited as long as the hydroxy group at the 6-position of β1,3-glucan can be replaced with a halogen group. Examples of the halogenating agent include a combination of triphenylphosphine and N-halosuccinimide, a combination of triphenylphosphine and carbon tetrahalogenate, and the like. The halogenating agent is preferably a combination of triphenylphosphine and N-halosuccinimide from the viewpoint of yield, ease of synthesis and the like.

The amount of the halogenating agent used varies depending on the type of the halogenating agent, but from the viewpoint of yield, ease of synthesis, etc., the total amount of the halogenating agent is usually 2 to 20 g per 1 g of the starting material. Is preferable, and 5 to 15 g is more preferable.

This step is preferably carried out in a solvent. As the solvent, for example, one or more polar solvents such as N, N-dimethylacetamide, N, N-dimethylformamide, dimethyl sulfoxide, and N-methylpyrrolidone can be used. The solvent is preferably N, N-dimethylacetamide from the viewpoint of yield, ease of synthesis and the like.

In this step, when N, N-dimethylacetamide is used, lithium halide is further added. Also, when other solvents are used, lithium halide is added as needed.

In this step, in addition to the above components, additives may be appropriately used as long as the effects of the present invention are not impaired.

As the reaction atmosphere, an inert gas atmosphere (argon gas atmosphere, nitrogen gas atmosphere, etc.) can be usually adopted. The reaction temperature can be either under heating or at room temperature, and is usually preferably 20 to 150 ° C. (particularly 50 to 100 ° C.). The reaction time is not particularly limited, and can be usually 10 minutes to 8 hours, preferably 1 hour to 6 hours.

After completion of the reaction, purification treatment can be carried out according to a conventional method, if necessary. Further, the next step can be performed without performing the purification treatment.

(2-2) β1,3-glucan derivative having partial structure B → β1,3-glucan derivative having partial structure C In this step, the β1,3-glucan derivative having partial structure B is reacted with an agitating agent. By doing so, a β1,3-glucan derivative having a partial structure C can be obtained.

The azidizing agent is not particularly limited as long as the halogen atom of the partial structure B can be replaced with an azido group. Examples of the azidizing agent include sodium azide, lithium azide and the like. As the azidizing agent, sodium azide is preferable from the viewpoint of yield, easiness of synthesis and the like.

The amount of the azidizing agent used varies depending on the type of the azidizing agent, but from the viewpoint of yield, ease of synthesis, etc., usually, 1 g of β1,3-glucan derivative having a partial structure B is used. 0.5 to 3 g is preferable, and 1 to 2 g is more preferable.

This step is preferably carried out in a solvent. As the solvent, for example, one or more polar solvents such as dimethyl sulfoxide, N, N-dimethylacetamide, N, N-dimethylformamide, and N-methylpyrrolidone can be used. The solvent is preferably dimethyl sulfoxide from the viewpoint of yield, ease of synthesis and the like.

In this step, in addition to the above components, additives may be appropriately used as long as the effects of the present invention are not impaired.

As the reaction atmosphere, an inert gas atmosphere (argon gas atmosphere, nitrogen gas atmosphere, etc.) can be usually adopted. The reaction temperature can be either under heating or at room temperature, and is usually preferably 20 to 150 ° C. (particularly 50 to 100 ° C.). The reaction time is not particularly limited, and can be usually 8 hours to 48 hours, preferably 16 hours to 32 hours.

After completion of the reaction, purification treatment can be carried out according to a conventional method, if necessary. Further, the next step can be performed without performing the purification treatment.

(2-3) β1,3-glucan derivative having partial structure C → β1,3-glucan derivative having partial structure D In this step, the β1,3-glucan derivative having partial structure C is reacted with a reducing agent. As a result, a β1,3-glucan derivative having a partial structure D can be obtained.

The reducing agent is not particularly limited as long as the azide group of the partial structure C can be reduced to the amino group. Examples of the reducing agent include hydrogen gas, sodium borohydride (NaBH ₄ ), sodium cyanoborohydride (NaBH ₃ CN) and the like. The reducing agent is preferably _{sodium borohydride (NaBH 4} ) from the viewpoint of yield, ease of synthesis and the like.

The amount of the reducing agent used varies depending on the type of reducing agent, but from the viewpoint of yield, ease of synthesis, etc., it is usually 2 to 2 to 1 g of β1,3-glucan derivative having partial structure C. 8 g is preferable, and 3 to 5 g is more preferable.

This step is preferably carried out in a solvent. As the solvent, for example, one or more polar solvents such as dimethyl sulfoxide, N, N-dimethylacetamide, N, N-dimethylformamide, and N-methylpyrrolidone can be used. The solvent is preferably dimethyl sulfoxide from the viewpoint of yield, ease of synthesis and the like.

In this step, in addition to the above components, additives may be appropriately used as long as the effects of the present invention are not impaired.

As the reaction atmosphere, an inert gas atmosphere (argon gas atmosphere, nitrogen gas atmosphere, etc.) can be usually adopted. The reaction temperature can be carried out under heating, at room temperature or under cooling, and is usually preferably carried out at 0 to 150 ° C. (particularly 70 to 120 ° C.). The reaction time is not particularly limited, and can be usually 8 hours to 48 hours, preferably 16 hours to 32 hours.

After completion of the reaction, purification treatment can be carried out according to a conventional method, if necessary. Further, the next step can be performed without performing the purification treatment.

3. 3. Use 1
Since the β1,3-glucan derivative of the present invention improves the causes of metabolic syndrome such as obesity and accumulation of visceral fat and has an action of improving metabolism of sugar and / or lipid, it is an agent for improving metabolism of sugar and / or lipid. It can be used as an active ingredient of. In this specification, glucose metabolism includes each of a series of phenomena from sugar intake to excretion. Further, in the present specification, lipid metabolism includes each of a series of phenomena from ingestion of a lipid or a substance convertible into a lipid to excretion of a lipid or a substance converted from the lipid.

In addition, other uses based on the metabolism improving action of sugars and / or lipids, for example, the uses listed below:
(A) A prophylactic or ameliorating agent for metabolic syndrome, or at least one disease or condition selected from the group consisting of dyslipidemia such as hypercholesterolemia and hyperlipidemia, diabetes, obesity, and fatty liver.
(B) Weight suppressant,
(C) Weight gain inhibitor,
(D) Body fat and / or visceral fat inhibitor,
(E) Inhibitor of increase in body fat and / or visceral fat,
(F) Fat consumption promoter,
(G) Blood lipids (eg cholesterol, triglycerides, etc.) and / or blood glucose suppressants,
(H) Blood lipids (eg cholesterol, triglycerides, etc.) and / or inhibitors of blood glucose elevation,
(I) Blood LDL cholesterol, total cholesterol inhibitor,
(J) Blood LDL cholesterol, inhibitor of total cholesterol elevation,
(K) Secondary bile acid inhibitor,
(L) Primary bile acid enhancer,
(M) Bile acid synthesis promoter,
(N) Preventive agent for metabolic diseases (O) Preventive agent for colorectal cancer (P) Preventive agent for liver cancer (Q) Treatment agent for infectious gastroenteritis (R) Improvement agent for hepatic encephalopathy, Ammonia suppressor (S) It can be used as an active ingredient such as a non-alcoholic steatohepatitis inhibitor (T) an intestinal flora regulator (U) an intestinal flora improver (H) an intestinal flora dysbiosis inducer.

Furthermore, the uses, purposes, and targets listed below:
(A) Reduce visceral fat (b) Suppress increase in body fat, reduce body fat, suppress fat absorption (c) Reduce triglyceride (e) Moderate rise in cholesterol level, or blood glucose level (F) Suppress sugar absorption, suppress sugar absorption (g) Lower blood cholesterol (j) For those who are concerned about visceral fat (k) For those with high BMI (l) For those with high triglyceride (m) For those who are concerned about cholesterol (n) For those with high (worrisome) postprandial blood glucose level.

In addition to visceral fat obesity, metabolic syndrome is one of two of (1) hypertension, (2) high blood sugar level, and (3) low HDL cholesterol or high triglyceride. It is a state that applies to one or more.

The agent of the present invention can be used in various fields as, for example, pharmaceuticals, food additives, food compositions (including health promoters, nutritional supplements (supplements, etc.)) and the like.

The form of the agent of the present invention is not particularly limited, and can take a form usually used in each application depending on the application.

As for the form, when the use is a medicine, a food additive, a health enhancer, a nutritional supplement (supplement, etc.), for example, a tablet (intraoral disintegrating tablet, chewable tablet, effervescent tablet, troche agent, jelly-like drop) Includes agents), pills, granules, fine granules, powders, hard capsules, soft capsules, dry syrups, liquids (including drinks, suspensions, syrups), jelly, etc. ..

In terms of form, when the application is a food composition, liquid, gel or solid foods such as juices, soft drinks, teas, soups, soy milk and other beverages, salad oils, dressings, yogurt, jellies, puddings, sprinkles, etc. Examples include soymilk for childcare, cake mixes, powdered or liquid dairy products, breads, cookies and the like.

The agent of the present invention may further contain other components, if necessary. The other ingredients are not particularly limited as long as they can be blended in medicines, food additives, food compositions, health enhancers, dietary supplements (supplements, etc.), and the like, but are not particularly limited, for example, bases and carriers. , Solvents, dispersants, emulsifiers, buffers, stabilizers, excipients, binders, disintegrants, lubricants, thickeners, colorants, fragrances, chelating agents and the like.

When the agent of the present invention contains a component other than the β1,3-glucan derivative of the present invention, the content of the active ingredient depends on the intended use, mode of use, state of application, etc., and is not limited. For example, it can be 0.0001 to 95% by mass, preferably 0.001 to 50% by mass.

The amount of the agent of the present invention applied to a target organism (for example, administration, ingestion, inoculation, etc.) is not particularly limited as long as it is an effective amount that exhibits a medicinal effect, and is usually β1,3- of the present invention, which is an active ingredient. The dry weight of the glucan derivative is generally 0.1 to 10000 mg / kg body weight per day. The above application amount is preferably applied once or more once a day (for example, 1 to 3 times), and can be appropriately increased or decreased depending on the age, pathological condition, and symptom.

Four. Use 2
The β1,3-glucan derivative of the present invention can exert an antibacterial action. Therefore, the β1,3-glucan derivative of the present invention can be suitably used as an active ingredient of an antibacterial agent. Further, the antibacterial agent of the present invention includes various compositions (external pharmaceutical compositions, cosmetic compositions, medical cleansing compositions, medical device compositions to be placed in the body and blood vessels, skin disinfectant compositions, etc. It may be blended with a tableware sterilizing / cleaning composition, an oral disinfecting composition, a surface antibacterial composition, etc.). Preferably, the antibacterial agent of the present invention can also be used as one component constituting an antibacterial material such as a wound healing agent and medical use.

The antibacterial agent of the present invention can be used for Gram-positive bacteria or Gram-negative bacteria regardless of the type of the applicable bacteria. Gram-positive bacteria to be applied include, for example, staphylococci (eg, yellow cocci, epidermis staphylococci), enterococci (eg, Enterococcus), streptococci (eg, diplococci, quadruple, octuplococcus). Etc., pneumoniae, hemolytic streptococcus), Basilus spp. (Ecococcus, Bacillus subtilis), Clostridium spp. Examples include spp., Bifidobacterium spp., Propionibacterium spp. (Eg. Applicable gram-negative bacteria include, for example, Escherichia (eg, Escherichia coli), Salmonella, Pseudomonas (eg, Pseudomonas aeruginosa), Helicobacter, Haemophilus influenzae, Neisseria (eg, gonococcus, meningococcus). Bacteria). Among these, the antibacterial agent of the present invention can be preferably used against Staphylococcus spp., Pseudomonas spp., Escherichia spp. And the like.

The antibacterial agent of the present invention is not particularly limited as long as it contains the β1,3-glucan derivative of the present invention, and may further contain other components if necessary. The other components are not particularly limited as long as they are pharmaceutically acceptable components, but are, for example, bases, carriers, solvents, dispersants, emulsifiers, buffers, stabilizers, excipients, and binders. , Disintegrants, lubricants, thickeners, moisturizers, colorants, fragrances, chelating agents and the like.

The mode of use of the antibacterial agent of the present invention is not particularly limited, and an appropriate mode of use can be adopted according to the type of the antibacterial agent. The agent of the present invention can be used, for example, by applying it to animals, or it can be used by applying it to other than living organisms (cells, members, instruments, etc.).

When the antibacterial agent of the present invention is applied to an animal, the target animal is not particularly limited, and examples thereof include various mammalian animals such as humans, monkeys, mice, rats, dogs, cats, and rabbits.

The dosage form of the antibacterial agent of the present invention is not particularly limited, and an appropriate dosage form can be taken depending on the mode of use thereof. Examples thereof include external preparations such as coating agents, patches, aerosol agents, nasal drops, inhalants, anal suppositories, inserts, enemas and jellies. Further, the agent of the present invention may be a solid agent, a semi-solid agent, or a liquid agent.

The content of the β1,3-glucan derivative of the present invention in the antibacterial agent of the present invention depends on the mode of use, application target, state of application target, etc., and is not limited, but is, for example, 0.0001 to 95 weight. %, preferably 0.001 to 50% by weight.

When the antibacterial agent of the present invention is applied to an animal, the amount applied is not particularly limited as long as it is an effective amount that exerts a medicinal effect, and is usually used as the weight of the β1,3-glucan derivative of the present invention as an active ingredient. 0.01 to 100 mg per day / Applicable part. The above application amount is preferably applied once a day or divided into 2 to 3 times, and can be appropriately increased or decreased depending on the age, pathological condition, and symptom.

When the antibacterial agent of the present invention is used as a wound healing agent, the wound healing agent is not particularly limited as long as it contains the antibacterial agent of the present invention. Typically, in addition to the antibacterial agent of the present invention, a component having a wound healing action is contained. The dosage form of the wound healing agent is not particularly limited, but for example, an external preparation such as a coating agent, a patch, an aerosol agent, a nasal drop agent, an inhalant, an anal suppository, an insert agent, an enema agent, and a jelly agent. And so on. Further, the wound healing agent may be in a form in which the antibacterial agent of the present invention is held on a sheet (or film) -like base material that protects the wound.

When the antibacterial agent of the present invention is used as an antibacterial material, the antibacterial material is not particularly limited as long as it contains the antibacterial agent of the present invention. The form of the antibacterial material is not particularly limited as long as the antibacterial agent of the present invention can exert its antibacterial action. Examples thereof include those obtained by coating the surface of a material such as resin, metal, or glass with the antibacterial agent of the present invention.

Hereinafter, the present invention will be described in detail based on examples, but the present invention is not limited to these examples.

Synthesis example 1: Synthesis of 6-amino-6-deoxyparamylon
Carbohydrate Polymer 122 (2015) According to the method described in 84-92., From paramylon, through intermediates (6-bromo-6-deoxyparamylon and 6-azido-6-deoxyparamylon), some glucose residue A paramylon derivative (6-amino-6-deoxyparamylon) in which the hydroxy group of the group was _{replaced with -NH 2 was synthesized.} Specifically, it was synthesized as follows.

Synthesis Example 1-1: 6-Bromo-6-deoxyparamylon Argon atmosphere, paramylon (200.00 g) with a weight average molecular weight of about 200,000, dimethylacetamide (10000 ml), and lithium bromide (639.10 g) are added. Stirred. The temperature was raised to 100 ° C. with stirring, and the mixture was further stirred for 4 hours. After stirring, it was confirmed that each component was dissolved, and then the mixture was allowed to cool. A solution of dimethylacetamide (2500 ml) containing triphenylphosphine (1298.00 g) and N-bromosuccinimide (879.00 g) was slowly added dropwise to the reaction mixture. The reaction mixture was heated to 70 ° C. and stirred for about 3 hours. After stirring and allowing to cool, the reaction mixture was slowly added dropwise to a mixed solvent of water and methanol (50.0 L, w / w = 1/1). After standing, it was filtered through a filter having a pore size of 3.0 μm to recover the solid content. The solids were dissolved in dimethyl sulfoxide (3500 ml) and the resulting solution was added dropwise to ethanol (17500 ml). The solids were collected by centrifugation (6000 rpm x 10 min). This reprecipitation operation with dimethyl sulfoxide and ethanol was performed again. Drying under reduced pressure (40 ° C.) gave the desired product (a paramylon derivative (6-bromo-6-deoxyparamylon) in which the hydroxy group of some glucose residues was replaced with -Br) (359.80 g).

Synthesis Example 1-2: 6-Azido-6-deoxyparamylon Argon atmosphere, 6-bromo-6-deoxyparamylon (359.00 g) and dimethyl sulfoxide (63000 ml) obtained in Synthesis Example 1-1 in a 20 L eggplant flask. And stirred. After confirming dissolution, sodium azide (516.90 g) and dimethyl sulfoxide (2700 ml) were added to the reaction mixture. The reaction mixture was heated to 80 ° C. and stirred for 24 hours. After stirring and allowing to cool, the reaction mixture was slowly added dropwise to ion-exchanged water (106 L). After standing, it was filtered through a filter having a pore size of 3.0 μm to recover the solid content. The solid content was dissolved in acetone (2500 ml) and the resulting solution was added dropwise to water (10000 ml). The solids were collected by centrifugation (6000 rpm x 10 min). This reprecipitation operation with acetone and water was performed again. Drying under reduced pressure (40 ° C.) gave the desired product (a paramylon derivative (6-azido-6-deoxyparamylon) in which _{the hydroxy group of some glucose residues was replaced with −N 3) (187.20 g).} .. As a result of confirming the obtained compound by IR and carbon NMR, a characteristic peak of azide ^{was confirmed at 2110 cm -1} from IR (Fig. 1), and a chemical shift (51 ppm) to carbon at the 6th position from carbon NMR was confirmed. (Nearby) was confirmed (Fig. 2). These are in agreement with the values reported in the previous report (Carbohydrate Polymer 122 (2015) 84-92.), And it was confirmed that the target product was certainly obtained.

Synthesis Example 1-3: 6-Amino-6-deoxyparamylon Argon atmosphere, 20 L eggplant of 6-azido-6-deoxyparamylon (185.70 g) and dimethyl sulfoxide (15000 ml) obtained in Synthesis Example 1-2 It was placed in a flask and stirred. After confirming dissolution, sodium borohydride (753.40 g) was added to the reaction mixture. The reaction mixture was heated to 100 ° C. and stirred for 24 hours. After allowing to cool to room temperature, 1N HCl was added to the reaction mixture in an ice bath until no gas was generated. The pH of the reaction mixture was adjusted to pH 7 with saturated aqueous sodium hydrogen carbonate solution. The reaction mixture was dialyzed against ion-exchanged water for 14 days (dialysis membrane: MWCO = 3.5 kD, solvent exchange twice / day). After dialysis, about 3/4 of the amount is concentrated, and the concentrated solution is freeze-dried to obtain the desired product (a paramylon derivative (6-amino-6) in which _{the hydroxy group of some glucose residues is replaced with -NH 2).} -Deoxyparamylon)) (151.50 g) was obtained. As a result of confirming the obtained compound by IR and carbon NMR, it was confirmed that the characteristic azide peak disappeared from IR and a large broad peak of about 3000 cm-1 which seems to indicate amine (). In addition, a chemical shift (around 44 ppm) was confirmed in carbon at the 6th position by carbon NMR (Fig. 4). These are in agreement with the values reported in the previous report (Carbohydrate Polymer 122 (2015) 84-92.), And it was confirmed that the target product was certainly obtained. Further, from FIG. 4, since the peak showing C6 of paramylon was completely converted after the reaction, it was found that only the hydroxyl group of C6 was substituted with amine and the degree of substitution was 1.

Test example 1. Analysis of effects on sugar and lipid metabolism 1
Mice were bred on the diet containing 6-amino-6-deoxyparamylon obtained in Synthesis Example 1, and the body weight, total food intake, total water intake, blood glucose level, and total blood cholesterol concentration were measured. .. Specifically, it was carried out as follows.

<Test Example 1-1. Feed preparation>
A test feed (2%) containing 2% by weight of a paramylon derivative by mixing 6-amino-6-deoxyparamylon obtained in Synthesis Example 1 with a powdered high-fat feed (manufactured by Research Diet, containing 60 kcla% fat). Was prepared. On the other hand, a control feed consisting of a powdered high-fat feed was prepared.

<Test Example 1-2. Experimental animals and breeding conditions>
An 8-week-old male C57BL / 6J mouse (manufactured by Charles River Laboratories, Japan) was used. They were fed a normal diet (MF Oriental yeast) and acclimated for about 1 week. After acclimatization, 9-week-old mice were randomly assigned to receive the test feed 6-amino-6-deoxyparamylon-containing feed and the control feed group.

In the test breeding, the mice were allowed to freely ingest the feed (test feed or control feed) and tap water for 5 weeks.

The breeding conditions are as follows. They were individually bred in aluminum cages (W220 x D320 x H110 mm) containing bedding (oriental yeast). The number of beds was changed at least twice a week, and was changed when feeding new feed. The room temperature was 25 ± 2 degrees, the humidity was 50 ± 10%, and the lighting was lit for 12 hours a day (7:00 to 19:00).

<Test Example 1-3. Measurement method, evaluation method>
<Test Example 1-3-1. Measurement of body weight, total food intake, total drinking water>
During the test breeding period, the body weight was measured at least twice a week. In addition, the total amount of food and water consumed during the test breeding period was measured.

<Test Example 1-3-2. Measurement of blood glucose level and total blood cholesterol level>
Mice were necropsied at the 5th week of test breeding. On the morning of the autopsy day, after weighing, the patient was fasted for 1-2 hours. The tail was cut under isoflurane anesthesia, venous blood was measured with a blood glucose measurement kit (manufactured by TERUMO), the abdomen was opened, and all blood was collected from the left ventricle with an EDTA-2N-treated syringe and then euthanized. The obtained blood was centrifuged at about 2,000 xg for about 10 minutes to collect plasma. The total cholesterol concentration in the obtained plasma was measured by gel filtration HPLC method.

<Test Example 1-4. Result>
<Test Example 1-4-1. Body weight, total food intake, total water intake, blood glucose level, and total blood cholesterol concentration>
FIG. 5 shows a graph of the changes in body weight during the test breeding period. Table 1 shows each data after the end of the test breeding period. In Table 1, the numerical values of each measurement item are the average value ± standard deviation, and the p value is the value obtained by the t-test. In addition, in these data, the test feed group is a group in which the test feed (2%) containing 2% by weight of the paramylon derivative was ingested.

As shown in FIG. 5 and Table 1, the test feed intake group significantly gained weight as compared with the control feed intake group, although there was no significant change in the total food intake and the total water intake. It was suppressed. Furthermore, the test feed intake group had significantly lower blood glucose levels and total cholesterol levels than the control feed intake group. From these facts, it was suggested that the intake of the test feed improved glucose metabolism and lipid metabolism.

Test example 2. Analysis of effects on sugar and lipid metabolism 2
The procedure was the same as in Test Example 1 except that the triglyceride concentration was measured instead of the total cholesterol concentration. The triglyceride concentration was measured by using an enzymatic method.

FIG. 6 shows a graph of the changes in body weight during the test breeding period. Table 2 shows each data after the end of the test breeding period. In Table 2, the numerical values of each measurement item are the average value ± standard deviation, and the p value is the value obtained by the t-test.

Similar results to Test Example 1 were obtained for body weight and blood glucose level. In addition, the triglyceride concentration was significantly lower in the test feed intake group than in the control feed intake group.

Test example 3. Analysis of effects on sugar and lipid metabolism 3
Mice were bred in the same manner as in Test Example 1 except that the test feed group (2%) containing 2% by weight of the paramylon derivative and the test feed group (1%) containing 1% by weight were ingested.

<Test Example 3-3. Measurement method, evaluation method>
<Test Example 3-3-1. Measurement of weight change>
During the test breeding period, the body weight was measured at least twice a week, and the amount of change in body weight before and after the breeding period of 5 weeks was calculated.

<Test Example 3-3-2. Evaluation of fatty liver inhibitory effect>
Mice were necropsied at week 5 of the test breeding and liver weight was measured. In addition, the obtained liver was stained with HE.

<Test Example 3-3-3. Evaluation of triglyceride excretion promoting effect>
Feces were collected in the 4th week of the test breeding, and the neutral fat in the feces was stained with Zudan IV stained powder.

<Test Example 3-3-4. Evaluation of bile acid synthesis promoting action>
Mice were necropsied at the 5th week of the test breeding, and the amount of CYP7A1 mRNA and the amount of SHP mRNA in hepatocytes were measured. CYP7A1 is the gene for the enzyme that catalyzes the initial reaction of the cholesterol-to-bile acid biosynthetic pathway, and SHP is the gene for the suppressor of CYP7A1 expression.

<Test Example 3-3-5. Evaluation of effects on bile acids>
Feces were collected in the 4th week of the test breeding, and the composition of bile acids in 1 gram of feces was measured by the LC-QTOF MS method.

<Test Example 3-3-6. Evaluation of gastrointestinal safety>
Five-week-old test-reared mice were dissected and sections of the stomach, ileum, colon, and rectum were prepared. These were stained with HE and the cell size, morphology, etc. were observed.

In addition, the amount of inflammation markers (IL-6 mRNA amount, MCP-1 mRNA amount, Col4α1 mRNA amount, TGF-β mRNA amount) in kidney cells was measured.

<Test Example 3-4. Results>
<Test Example 3-4-1. Weight change>
Table 3 shows the amount of change in body weight and the total amount of food intake after the end of the test period.

The amount of change in body weight tended to be similar to that of the previous test results. Significant differences were observed between the target feed group and the test feed group (1%), and between the target feed group, the test feed group (1%) and the test feed group (2%). (P <0.05). On the other hand, there was no significant difference in total food intake.

<Test Example 3-4-2. Fatty liver inhibitory effect>
The HE-stained image of the liver is shown in FIG. 7, and the measurement results of the liver weight and the white adipose tissue weight are shown in FIG. Compared with the control feed group, the liver weight and the white adipose tissue weight were significantly reduced in the test feed group. When the liver was confirmed by HE staining, it was confirmed that the liver was enlarged due to fat in the control feed group, but it was confirmed that the liver was normal in the test feed group.

<Test Example 3-4-3. Triglyceride excretion promoting effect>
FIG. 9 shows a stained image of triglyceride in feces using Zudan IV stained powder. It was confirmed that triglycerides were mixed in the feces in the test feed group as compared with the control feed group. It was suggested that the intake of test feed suppressed the absorption of triglycerides.

<Test Example 3-4-4. Bile acid synthesis promoting action>
The measurement result of the expression level of the bile acid synthesis-related gene is shown in FIG. The amount of SHP mRNA was significantly decreased and the amount of CYP7A1 mRNA was significantly increased in the test feed group as compared with the control feed group. It was considered that the intake of the test feed decreased SHP, which is an expression-suppressing factor of CYP7A1, and as a result, increased CYP7A1. From this result, it was found that the intake of the test feed promoted the synthesis of bile acids.

<Test Example 3-4-5. Effects on bile acids>
The measurement result of the bile acid composition in 1 gram of feces is shown in FIG. It was found that the control feed group contained secondary bile acids in feces, but the test feed group contained almost no secondary bile acids and the concentration of primary bile acids was high. From this, it was found that the secondary bile acid is usually produced from the primary bile acid, whereas the secondary bile acid is hardly synthesized and produced mainly by the primary bile acid when the test feed is ingested. This result is considered to be due to the change in the intestinal bacterial flora due to the intake of the test feed.

It is known that by suppressing the amount of secondary bile acid, it is possible to prevent diabetes and metabolic diseases, as well as colorectal cancer and liver cancer. Therefore, it was suggested that the test feed had these preventive effects.

<Test Example 3-4-6. Safety to the digestive tract>
HE-stained images of the stomach, ileum, colon, and rectum are shown in FIG. When the cells were observed, no particular abnormality was observed in the test feed intake group. When the amount of IL-6 mRNA, MCP-1 mRNA, Col4α1 mRNA, and TGF-β mRNA in the kidney cells were measured, no significant difference was observed, and it was found that no abnormality was observed in the kidney.

Test Example 4: Evaluation of antibacterial activity Previously reported literature (cationization of cellulose fibers with n-alkyl, 3-chloro-2-hydroxypropyl, ammonium chlorides and their antibacterial activity, by Yuko Sawa et al., Mukogawa Women's University Bulletin 2000, 48, With reference to 19-26), an evaluation test of the antibacterial activity of the test substance (6-amino-6-deoxyparamylon obtained by the same method as in Synthesis Example 1) was conducted by the modified contact shaking method. .. Specifically, the procedure shown below was performed.

<Procedure>
(1) The test bacteria (S. aureus, S. epidermidis, P. aeruginosa, or E. coli) were cultured in LB medium at 35 ° C. with shaking overnight.
(2) The culture solution of the test bacterium was collected and centrifuged (10000 g, 25 ° C, 5 min).
(3) The supernatant was discarded and suspended in pure water.
(4) The suspension of (3) was inoculated to a concentration of 10% (suspension volume of (3) / aqueous solution volume of test substance) with respect to various concentrations of the test substance aqueous solution.
(5) A similar experiment was conducted on sterilized water containing no test substance as a control system.
(6) The cells were cultured with reciprocating shaking at 35 ° C. and 120 rpm for 1 hour.
(7) After being arbitrarily diluted with pure water, it was plated on a standard agar medium.
(8) Twenty-four hours after (7), the number of colonies was counted, and the number of surviving bacteria was determined using a sample containing no test substance as a control system.

The results are shown in Table 4.

As shown in Table 4, 6-amino-6-deoxyparamylon was shown to exert antibacterial activity (particularly bactericidal activity) against various bacteria in a concentration-dependent manner.

Claims (11)

A β1,3-glucan derivative in which at least one hydroxy group of at least some glucose residues is -NR ¹ R ² (R ¹ and R ² are independent hydrogen atoms or carbon atoms at each appearance. An agent for improving the metabolism of sugars and / or lipids, which comprises a β1,3-glucan derivative substituted with (showing an alkyl group of numbers 1 to 6). The metabolism improving agent according to claim 1, wherein the hydroxy group is a 6-position hydroxy group. The metabolism improving agent according to claim 1 or 2, wherein R ¹ and R ^{2 are hydrogen atoms.} The metabolism improving agent according to any one of claims 1 to 3, wherein the β1,3-glucan derivative is a paramylon derivative or a curdlan derivative. The metabolism improving agent according to any one of claims 1 to 4, wherein the β1,3-glucan derivative is linear and all the bonds between sugar residues are β1,3-glucoside bonds. The metabolism improving agent according to any one of claims 1 to 5, which is used for improving both glucose metabolism and lipid metabolism. The metabolism improving agent according to any one of claims 1 to 6, which is a pharmaceutical. The metabolism improving agent according to any one of claims 1 to 7, which is used for prevention or amelioration of at least one selected from the group consisting of (1) metabolic syndrome or (2) obesity, diabetes, and dyslipidemia. For use as a sugar and / or lipid metabolism improver,
A β1,3-glucan derivative in which at least one hydroxy group of at least some glucose residues is -NR ¹ R ² (R ¹ and R ² are independent hydrogen or carbon atoms at each appearance. A β1,3-glucan derivative obtained by substituting an alkyl group of numbers 1 to 6). A β1,3-glucan derivative in which at least one hydroxy group of at least some glucose residues is -NR ¹ R ² (R ¹ and R ² are independent hydrogen or carbon atoms at each appearance. A method for improving glucose and / or lipid metabolism, which comprises applying a β1,3-glucan derivative substituted with (1 to 6) an alkyl group to the subject. For producing sugar and / or lipid metabolism improvers,
A β1,3-glucan derivative in which at least one hydroxy group of at least some glucose residues is -NR ¹ R ² (R ¹ and R ² are independent hydrogen or carbon atoms at each appearance. Use of β1,3-glucan derivative which is replaced by (indicating an alkyl group of numbers 1 to 6).

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