Use of enzymatically modified isoquercitrin

Abstract

The present invention provides a saliva secretion stimulating agent having a dosage form usable in the oral cavity or a dosage form usable by oral administration (dosage form for the oral cavity, dosage form for oral administration). The saliva secretion stimulating agent can be prepared using enzyme-modified isoquercitrin or a combination of enzyme-modified isoquercitrin and a thickening polysaccharide. The present invention also provides an additive (additive for oral composition) that is effective for preparing an oral composition (food or beverage, pharmaceutical product for oral administration) and can impart at least one activity selected from the group consisting of saliva secretion stimulating activity, swallowing improvement activity (swallowing aid activity), and mastication improvement activity (mastication aid activity) to the oral composition. The additive can be prepared using a combination of enzyme-modified isoquercitrin and a thickening polysaccharide.

Description

TECHNICAL FIELD

[0001] The present application relates to the use of enzyme-modified isoquercitrin. More specifically, the present application relates to the use of enzyme-modified isoquercitrin as a sialagogue, in particular as a sialagogue in a form for use in the oral cavity (a form for intraoral use), or in a form for use by oral administration (a form for oral administration).

[0002] The present application also relates to the use of enzyme-modified isoquercitrin as an additive for a composition (e.g., a food or beverage or a pharmaceutical product) for intraoral use or oral ingestion in order to impart at least one action selected from the group consisting of a saliva secretion promoting action, a swallowing improving action (swallowing assisting action), and a mastication improving action (mastication assisting action) to the composition. BACKGROUND

[0003] Saliva plays an important role in, for example, oral cavity functions and maintenance of the intraoral environment. Examples of oral cavity functions include functions that make enunciation and conversation smoother, food intake functions, and swallowing functions. In particular, with respect to food or beverage intake functions and swallowing functions, saliva is deeply involved in the action of forming a bolus, digestive activity by amylase secretion, and the action of maintaining taste by dissolving tastants and secreting carbonic anhydrase. Furthermore, in order to maintain the intraoral environment, saliva is deeply involved in self-cleaning action in the oral cavity (including the teeth), tooth remineralization action, antibacterial action, immune action, anti-inflammatory action, and tissue repair promotion action by growth factors, etc.

[0004] However, it is known that the amount of saliva secretion decreases due to various diseases, such as mood and stress disorders, neurosis, organ dysfunction, encephalitis, tumors, cerebrovascular diseases, hypertension, Basedow's disease, and diabetes; side effects of drugs; radiation therapy; aging; etc. In particular, in elderly people, not only does aging decrease the function of salivary glands, but also various chronic diseases and therapeutic agents for such diseases decrease the amount of saliva secretion; thus, many people currently complain of dry mouth.

[0005] Decreased saliva secretion dries the oral cavity, which results in difficulty in mastication and swallowing, and decreases digestive function. Dry mouth also causes an unpleasant sensation in the oral cavity, and halitosis. Further development of such symptoms leads to periodontal disease and infectious diseases in the oral cavity, such as stomatitis. Therefore, there is a need to increase the amount of saliva secretion by some means.

[0006] As a means for increasing the amount of saliva secretion, a taste stimulation method using acidification (Patent Literature (PTL) 1) and an olfactory stimulation method (PTL 2) have been proposed. A method using a plant extract or a component of a plant extract having a saliva secretion promoting effect (PTL 3 to PTL 8), a method using a drug substance targeting muscarinic receptors (PTL 9), and a method using a drug substance targeting PAR-2 (PTL 10) have also been proposed.

[0007] However, some of the methods disclosed in the above documents are insufficient in terms of the strength and persistence of the action, and also have the following problems.

[0008] The method disclosed in PTL 1 is only useful for limited use in terms of palatability. Furthermore, due to the strong stimulation, frequent use of the method can affect oral tissues, such as tooth dissolution, oral mucosa irritation, and the like. The method disclosed in PTL 2 has a problem in that the action is lost with the disappearance of the olfactory stimulation. The methods disclosed in PTL 3 to PTL 6 have a problem in that the methods are only applicable to limited types of compositions (food compositions and compositions for use in the oral cavity) because many of the plant extracts used in these methods have specific stimulation, taste, and flavor, and such extracts must or are recommended to be used with organic acids. Furthermore, the methods disclosed in PTL 9 and PTL 10 use drug substances; therefore, the use of such methods can be limited.

[0009] Quercetin, a flavonoid, has recently been reported to have a saliva secretion enhancing effect (Non Patent Literature (NPL) 1). More specifically, it has been reported that administration of quercetin to model mice having a saliva secretion disorder caused by radiation exposure reduced hyposalivation, and administration of quercetin to normal mice enhanced saliva secretion. Regarding the mechanism of action of quercetin in saliva secretion, NPL 1 discloses that saliva secretion is promoted by enhancing the expression of aquaporin 5 and ion uptake into cells. However, these are data from mice ingesting quercetin. NPL 1 makes no mention of the case of human ingestion of quercetin.

[0010] Bibliographic List

[0011] Patent Literature

[0012] PTL 1: JPH7-101856A

[0013] PTL 2: JP2003-40752A

[0014] PTL 3: JPH11-71253A

[0015] PTL 4: JPH10-182392A

[0016] PTL 5: JP 2002-265375 A

[0017] PTL 6: JP 2003-162633 A

[0018] PTL 7: WO 2009 / 060915

[0019] PTL 8: JP 2009-531287 A

[0020] PTL 9: JP H8-12575 A

[0021] PTL 10: JP 2001-64203 A

[0022] Non Patent Literature (NPL)

[0023] Non Patent Literature (NPL) 1: Ichiro Saito et al., PLOS ONE, DOI, 10.1371 / journal.pone.0116008. January 28, 2015 SUMMARY

[0024] PROBLEMS TO BE SOLVED BY THE INVENTION

[0025] An object of the present application is to provide a sialagogue, preferably a sialagogue which is used for the oral cavity of a human or by oral administration to a human; and to rapidly promote salivation after administration or oral intake (ingestion) of the sialagogue in the oral cavity, and to cure dry mouth.

[0026] Further, another object of the present application is to provide an additive effective in the production of a composition for use in the oral cavity or for oral ingestion (food or beverage, pharmaceutical product) which is capable of promoting salivation; and preferably an additive effective in the production of a composition for use in the oral cavity or for oral ingestion which is capable of promoting salivation and assisting mastication and swallowing in a human in whom the salivation function is decreased. The additive is preferably an additive for a composition for use in the oral cavity or for oral ingestion which can impart the above-mentioned effects to the composition for use in the oral cavity or for oral ingestion without giving an undesirable stimulation or flavor (taste, odor) to the oral cavity, or providing a side effect harmful to the human body. Another object of the present application is to provide a method for producing a composition for use in the oral cavity or for oral ingestion by using the additive. Another object of the present application is to provide a composition for use in the oral cavity or for oral ingestion comprising the additive.

[0027] SOLUTION TO THE PROBLEM

[0028] The present inventors conducted extensive research to achieve the above object, and found that enzyme-modified isoquercitrin has a saliva secretion promoting effect. More specifically, as shown in Experimental Example 1 described below, the present inventors found that application of enzyme-modified isoquercitrin to the oral cavity of a human, or oral ingestion of enzyme-modified isoquercitrin, immediately promotes saliva secretion and increases the amount of secretion. In contrast, when α-glucosylquercetin, which is a quercetin glycoside having a quercetin structure like enzyme-modified isoquercitrin, or quercetin itself was applied to a human in an equimolar amount relative to enzyme-modified isoquercitrin (converted to rutin), no saliva secretion promoting effect (saliva secretion increasing effect) was confirmed. These results demonstrate that, among the above-described flavonoids, only enzyme-modified isoquercitrin exhibits a saliva secretion promoting effect (saliva secretion increasing effect) immediately upon application to the oral cavity of a human or oral administration to a human, and that this effect is specific to enzyme-modified isoquercitrin. Furthermore, as shown in Experimental Example 2, the saliva secretion promoting effect (saliva secretion increasing effect) of enzyme-modified isoquercitrin was significantly improved by thickening enzyme-modified isoquercitrin with a polysaccharide, or by thickening the test sample. This enhancement of the saliva secretion promoting effect (saliva secretion increasing effect) by incorporation of a thickening polysaccharide or by thickening was also specific to enzyme-modified isoquercitrin, and was not observed in α-glucosylquercetin or quercetin itself.

[0029] The present inventors conducted further research based on this finding and confirmed that, in particular, when a thickening polysaccharide is used at a ratio of 0.2 to 500 parts by mass per 1 part by mass of enzyme-modified isoquercitrin, the saliva secretion promoting effect of enzyme-modified isoquercitrin can be enhanced without significantly affecting the palatability (taste, odor, etc.) of the target composition (food or beverage, composition) for use in the oral cavity or for oral ingestion.

[0030] The present inventors conducted further research based on these findings, and completed the present application. The present application includes the following embodiments.

[0031] (A) Use as a sialogogue

[0032] (A-I) Sialogogue

[0033] (A-I-1) A saliva stimulant comprising enzyme-modified isoquercitrin as an active ingredient.

[0034] (A-I-2) The saliva stimulant according to (I-1), further comprising a thickening polysaccharide.

[0035] (A-I-3) The salivation agent according to (A-I-1) or (A-I-2), wherein the thickening polysaccharide is at least one selected from the group consisting of xanthan gum, locust bean gum, guar gum, tara gum, deacylated gellan gum, highly acylated gellan gum, pectin, alginate, gelatin, agar, psyllium gum, and carrageenan.

[0036] (A-I-4) The salivation agent according to any one of (A-I-1) to (A-I-3), which is a composition for intraoral use or oral intake.

[0037] (A-I-5) The salivation agent according to any one of (A-I-1) to (A-I-4), which is a composition for intraoral use or oral intake, for a person with reduced salivation function (a person with reduced salivation function) or a person with reduced swallowing function (a person with reduced swallowing function).

[0038] (A-I-6) The salivation agent according to any one of (A-I-1) to (A-I-5), which is a composition for intraoral use or oral intake, for a healthy person with a dry mouth. The dry mouth is not particularly limited. Examples include a mouth in a dry state at the time of exercise, bathing, wakefulness, and the like.

[0039] (A-I-7) The salivation agent according to any one of (A-I-1) to (A-I-6), wherein the salivation agent is in the form of a syrup, a health drink, a liquid, an emulsion, an oil, a spray, a gel, a paste, a tablet, a chewable, a lozenge, a pill, a granule, a powder (powdered drug), a dry syrup, a film, or a stick preparation.

[0040] The "salivation agent" of the present application promotes salivation, thereby exerting an effect of increasing the amount of salivation. In this sense, embodiments of the present application include a "salivation (amount) increasing agent".

[0041] (A-II) Process for the preparation of a sialogogue

[0042] (A-II-1) A method for preparing a salivation agent, comprising incorporating enzyme-modified isoquercitrin.

[0043] (A-II-2) The method according to (A-II-I), further comprising incorporating a thickening polysaccharide.

[0044] (A-II-3) The method according to (A-II-I) or (A-II-2), wherein the thickening polysaccharide is at least one selected from the group consisting of xanthan gum, locust bean gum, guar gum, tara gum, deacylated gellan gum, highly acylated gellan gum, pectin, alginate, gelatin, agar, psyllium gum, and carrageenan.

[0045] (A-II-4) The method according to any one of (A-II-I) to (A-II-3), further comprising processing the sialagogue into a form for intra-oral use or oral administration.

[0046] (A-II-5) The method according to any one of (A-II-I) to (A-II-4), wherein the form for intra-oral use or oral administration is a syrup, a health drink, a liquid, an emulsion, an oil, a spray, a gel, a paste, a tablet, a chewable, a lozenge, a pill, a granule, a powder (dispersible), a dry syrup, a film, or a stick preparation.

[0047] (A-III) Use for the production of a sialogogue

[0048] (A-III-1) Use of an enzyme-modified isoquercitrin for the production of a sialagogue.

[0049] (A-III-2) Use of an enzyme-modified isoquercitrin and a thickening polysaccharide for the production of a sialagogue.

[0050] (A-III-3) The use according to (A-III-2), wherein in the production of a sialagogue, the enzyme-modified isoquercitrin and the thickening polysaccharide are used alone, or in the form of a composition.

[0051] (A-III-4) The use according to (A-III-2) or (A-III-3), wherein the thickening polysaccharide is at least one selected from the group consisting of xanthan gum, locust bean gum, guar gum, tara gum, deacylated gellan gum, highly acylated gellan gum, pectin, alginate, gelatin, agar, psyllium gum, and carrageenan.

[0052] (A-III-5) The use according to any one of (A-III-I) to (A-III-4), wherein the sialagogue is in a form for intra-oral use or oral administration.

[0053] (A-III-6) The use according to any one of (A-III-I) to (A-III-5), wherein the form for intra-oral use or oral administration is a form of a syrup, a health drink, a liquid, an emulsion, an oil, a spray, a gel, a paste, a tablet, a chewable, a lozenge, a pill, a granule, a powder (dispersible), a dry syrup, a film, or a stick preparation.

[0054] (A-IV) Process for the promotion of salivation

[0055] (A-IV-I) The method for promoting salivation in a subject, comprising orally administering to the subject an effective amount of a sialagogue according to any one of (A-I-I) to (A-I-6).

[0056] (A-IV-2) The method according to (A-IV-1), wherein the subject is a human with reduced salivary secretion function (a human with reduced salivary secretion function) or a human with reduced swallowing function (a human with reduced swallowing function).

[0057] (A-IV-3) The method according to (A-IV-1) or (A-IV-2), wherein the subject is a human with hyposalivation or xerostomia.

[0058] (A-IV-4) The method according to any one of (A-IV-1) to (A-IV-3), wherein the subject is a healthy human whose oral cavity is in a dry state. The oral cavity in a dry state is not particularly limited. Examples include an oral cavity in a dry state at the time of exercise, bathing, being awake, and the like.

[0059] The "method for promoting salivary secretion" of the present application also achieves the effect of increasing the amount of salivary secretion by carrying out the method. In this sense, the present application also includes a "method for increasing salivary secretion (amount)".

[0060] (B) Use as an additive for a composition for intraoral use or oral ingestion

[0061] (I) Additive for a composition for intraoral use or oral ingestion

[0062] (B-I-1) An additive for a composition for intraoral use or oral ingestion, comprising enzyme-modified isoquercitrin and a thickening polysaccharide.

[0063] (B-I-2) An additive for a composition for intraoral use or oral ingestion according to (B-I-1), wherein the thickening polysaccharide is at least one selected from the group consisting of xanthan gum, locust bean gum, guar gum, tara gum, deacylated gellan gum, highly acylated gellan gum, pectin, alginate, gelatin, agar, psyllium gum, and carrageenan.

[0064] (B-I-3) An additive for a composition for intraoral use or oral ingestion according to (B-I-1) or (B-I-2), which contains the thickening polysaccharide at a ratio of 0.2 to 500 parts by mass per 1 part by mass of enzyme-modified isoquercitrin.

[0065] (B-I-4) An additive for a composition for intraoral use or oral ingestion according to (B-I-1) or (B-I-2), which is an additive for preparing a sol composition for intraoral use or oral ingestion, and contains the thickening polysaccharide at a ratio of 0.2 to 400 parts by mass, preferably 0.3 to 350 parts by mass, and more preferably 0.4 to 300 parts by mass, per 1 part by mass of enzyme-modified isoquercitrin.

[0066] (B-I-5) The additive for a composition for use in the oral cavity or oral ingestion according to (B-I-1) or (B-I-2), which is an additive for preparing a gel composition for use in the oral cavity or oral ingestion, and contains a thickening polysaccharide at a ratio of 1 to 500 parts by mass, preferably 2 to 450 parts by mass, and more preferably 2.5 to 350 parts by mass, per part by mass of the enzyme-modified isoquercitrin.

[0067] (B-I-6) The additive for a composition for use in the oral cavity or oral ingestion according to (B-I-1) or (B-I-2), which is an additive for preparing a processed cereal food or beverage, and contains the enzyme-modified isoquercitrin at a ratio of 0.01 to 3000 parts by mass, preferably 0.05 to 2000 parts by mass, and more preferably 0.1 to 1200 parts by mass, per part by mass of the enzyme-modified isoquercitrin.

[0068] (B-I-7) The additive for a composition for use in the oral cavity or oral ingestion according to any one of (B-I-1) to (B-I-6), which is an additive in at least one form selected from the group consisting of a solid agent, a paste, and a liquid agent.

[0069] (B-I-8) The additive for a composition for use in the oral cavity or oral ingestion according to any one of (B-I-1) to (B-I-7), wherein the composition for use in the oral cavity or oral ingestion is a food or beverage or a pharmaceutical product.

[0070] (B-I-9) The additive for a composition for use in the oral cavity or oral ingestion according to any one of (B-I-1) to (B-I-8), wherein the composition for use in the oral cavity or oral ingestion is a food or beverage or a pharmaceutical product that is ingested or administered to at least one person selected from the group consisting of a person with reduced salivary secretion function, a person with reduced swallowing function, and a person with reduced mastication function.

[0071] (B-I-10) The additive for a composition for use in the oral cavity or oral ingestion according to any one of (B-I-1) to (B-I-9), which is an additive for preparing a composition for use in the oral cavity or oral ingestion in a gel form having at least one of the following physical properties (1) and (2) or in a sol form having the following physical property (3):

[0072] (1) Breaking strain: 0.3 to 0.8;

[0073] (2) Hardness: 500 to 500,000 N / m 2 ; and

[0074] (3) Viscosity: 0.006 to 0.6 Pa s.

[0075] (B-I-11) The additive for the composition for use in the oral cavity or for oral ingestion according to any one of (B-I-1) to (B-I-10), which is used for one of (a) to (c) below:

[0076] (a) a salivation agent which imparts a salivation-promoting effect to the composition for use in the oral cavity or for oral ingestion:

[0077] The salivation agent can be preferably used for the preparation of the composition for use in the oral cavity or for oral ingestion (food or beverage, pharmaceutical product) for a person with reduced salivation function (person with reduced salivation function);

[0078] (b) a swallowing aid which imparts a swallowing-easy property to the composition for oral ingestion:

[0079] The swallowing aid can be preferably used for the preparation of the composition for oral ingestion (food or beverage, pharmaceutical product) for a person with reduced swallowing function (person with reduced swallowing function); and

[0080] (c) a mastication aid which imparts a mastication-easy property to the composition for oral ingestion:

[0081] The mastication aid can be preferably used for the preparation of the composition for oral ingestion (food or beverage, pharmaceutical product) for a person with reduced mastication function (person with reduced mastication function).

[0082] (B-II) Composition for intraoral use or oral ingestion and process for its preparation (B-II-1) The composition for use in the oral cavity or for oral ingestion, which comprises the additive for the composition for use in the oral cavity or for oral ingestion according to any one of (B-I-1) to (B-I-11).

[0083] (B-II-2) The composition for use in the oral cavity or for oral ingestion according to (B-II-1), which is a food or beverage, or a pharmaceutical product.

[0084] (B-II-3) The composition for use in the oral cavity or for oral ingestion according to (B-II-1) or (B-II-2), which is a food or beverage or a pharmaceutical product which is ingested or administered to at least one person selected from the group consisting of a person with reduced salivation function, a person with reduced swallowing function, and a person with reduced mastication function.

[0085] (B-II-4) The composition for use in the oral cavity or for oral ingestion according to any one of (B-II-1) to (B-II-3), which is a food or beverage for a healthy person whose oral cavity is in a dry state.

[0086] The oral cavity in a dry state is not particularly limited. Examples include an oral cavity in a dry state at the time of exercise, bathing, wakefulness, and the like.

[0087] (B-II-5) The composition for use in the oral cavity or for oral ingestion according to any one of (B-II-1) to (B-II-4), which is a food or beverage for use in the oral cavity or for oral ingestion or a pharmaceutical product in a gel form having at least one of the following physical properties (1) and (2) or a sol form having the following physical property (3):

[0088] (1) Strain at break: 0.3 to 0.8

[0089] (2) Hardness: 500 to 500,000 N / m 2

[0090] (3) Viscosity: 0.006 to 0.6 Pa-s.

[0091] (B-II-6) The method for producing a composition for use in the oral cavity or for oral ingestion according to any one of (B-II-1) to (B-II-5), which comprises incorporating an enzyme-modified isoquercitrin and a thickening polysaccharide, or an additive for a composition for use in the oral cavity or for oral ingestion according to any one of (B-I-1) to (B-I-11), into a food or beverage for use in the oral cavity or for oral administration or a pharmaceutical product each having a water content of 60 mass% or more.

[0092] (B-III) Multiple applications of enzyme-modified isoquercitrin

[0093] (B-III-1-1) A method for enhancing the saliva secretion promoting action of an enzyme-modified isoquercitrin, characterized by using a thickening polysaccharide and an enzyme-modified isoquercitrin.

[0094] (B-III-1-2) The enhancement method according to (B-III-1-1), wherein the thickening polysaccharide is at least one selected from the group consisting of xanthan gum, locust bean gum, guar gum, tara gum, deacylated gellan gum, highly acylated gellan gum, pectin, alginate, gelatin, agar, psyllium gum, and carrageenan.

[0095] (B-III-1-3) The enhancement method according to (B-III-1-1) or (B-III-1-2), wherein the thickening polysaccharide is used at a ratio of 0.2 to 500 parts by mass per one part by mass of the enzyme-modified isoquercitrin.

[0096] (B-III-1-4) The enhancement method according to any one of (B-III-1-1) to (B-III-1-3), which comprises forming a gel having at least one of the following physical properties (1) and (2) or a sol having the following physical property (3) by using a thickening polysaccharide and an enzyme-modified isoquercitrin: (1) Strain at break: 0.3 to 0.8;

[0097] (2) Hardness: 500 to 500,000 N / m 2 ; and

[0098] (3) Viscosity: 0.006 to 0.6 Pa-s.

[0099] (B-III-1-5) The enhancement method according to (B-III-1-4), which comprises forming a sol by using a thickening polysaccharide at a ratio of 0.2 to 400 parts by mass, preferably 0.3 to 350 parts by mass, and more preferably 0.4 to 300 parts by mass, per one part by mass of the enzyme-modified isoquercitrin.

[0100] (B-III-1-6) The enhancement method according to (B-III-1-4), which comprises forming a gel by using a thickening polysaccharide at a ratio of 1 to 500 parts by mass, preferably 2 to 450 parts by mass, and more preferably 2.5 to 350 parts by mass, per one part by mass of the enzyme-modified isoquercitrin.

[0101] (B-III-1-7) The enhancement method according to any one of (B-III-1-1) to (B-III-1-4), which comprises preparing a processed cereal food or beverage, wherein the processed cereal food or beverage contains a thickening polysaccharide at a ratio of 0.01 to 3000 parts by mass, preferably 0.05 to 2000 parts by mass, and more preferably 0.1 to 1200 parts by mass, per one part by mass of the enzyme-modified isoquercitrin.

[0102] (B-III-2-1) A method for promoting salivation in a person having a decreased salivation function, which comprises allowing a composition for intraoral use or oral intake containing enzyme-modified isoquercitrin and a thickening polysaccharide to be administered orally to or ingested by the person having a decreased salivation function.

[0103] (B-III-2-2) The salivation-promoting method according to (B-III-2-1), wherein the thickening polysaccharide is at least one selected from the group consisting of xanthan gum, locust bean gum, guar gum, tara gum, deacylated gellan gum, highly acylated gellan gum, pectin, alginate, gelatin, agar, psyllium gum, and carrageenan.

[0104] (B-III-2-3) The salivation-promoting method according to (B-III-2-1) or (B-III-2-2), wherein the composition for intraoral use or oral intake contains a thickening polysaccharide at a ratio of 0.2 to 500 parts by mass per one part by mass of the enzyme-modified isoquercitrin.

[0105] (B-III-2-4) The saliva secretion promoting method according to (B-III-2-1) or (B-III-2-2), wherein the composition for intraoral use or oral ingestion is in the form of a sol and contains a thickening polysaccharide at a ratio of 0.2 to 400 parts by mass, preferably 0.3 to 350 parts by mass, and more preferably 0.4 to 300 parts by mass, per part by mass of the enzyme-modified isoquercitrin.

[0106] (B-III-2-5) The saliva secretion promoting method according to (B-III-2-4), wherein the composition for intraoral use or oral ingestion is in the form of a gel and contains a thickening polysaccharide at a ratio of 1 to 500 parts by mass, preferably 2 to 450 parts by mass, and more preferably 2.5 to 350 parts by mass, per part by mass of the enzyme-modified isoquercitrin.

[0107] (B-III-2-6) The saliva secretion promoting method according to (B-III-2-4), wherein the composition for intraoral use or oral ingestion is a processed cereal food or beverage and contains a thickening polysaccharide at a ratio of 0.01 to 3000 parts by mass, preferably 0.05 to 2000 parts by mass, and more preferably 0.1 to 1200 parts by mass, per part by mass of the enzyme-modified isoquercitrin.

[0108] (B-III-2-7) The saliva secretion promoting method according to any one of (B-III-2-1) to (B-III-2-6), wherein the composition for intraoral use or oral ingestion is a food or beverage or a pharmaceutical product.

[0109] (B-III-2-8) The saliva secretion promoting method according to any one of (B-III-2-1) to (B-III-2-7), wherein the composition for intraoral use or oral ingestion is a food or beverage or a pharmaceutical product in the form of a gel having at least one of the following physical properties (1) and (2) or in the form of a sol having the following physical property (3):

[0110] (1) Breaking strain: 0.3 to 0.8;

[0111] (2) Hardness: 500 to 500,000 N / m 2 ; and

[0112] (3) Viscosity: 0.006 to 0.6 Pa-s.

[0113] (B-III-3-1) A composition for intraoral use or oral ingestion, which contains enzyme-modified isoquercitrin and a thickening polysaccharide, for use in improving a decrease in saliva secretion or promoting saliva secretion in a person with a decreased saliva secretion function.

[0114] (B-III-3-2) The composition for intraoral use or oral ingestion according to (B-III-3-1), wherein the thickening polysaccharide is at least one selected from the group consisting of xanthan gum, locust bean gum, guar gum, tara gum, deacylated gellan gum, highly acylated gellan gum, pectin, alginate, gelatin, agar, psyllium gum, and carrageenan.

[0115] (B-III-3-3) The composition for intraoral use or oral ingestion according to (B-III-3-1) or (B-III-3-2), wherein the composition for intraoral use or oral ingestion contains a thickening polysaccharide at a ratio of 0.2 to 500 parts by mass per part by mass of the enzyme-modified isoquercitrin.

[0116] (B-III-3-4) The composition for intraoral use or oral ingestion according to (B-III-3-1) or (B-III-3-2), which is in the form of a sol and contains a thickening polysaccharide at a ratio of 0.2 to 400 parts by mass, preferably 0.3 to 350 parts by mass, and more preferably 0.4 to 300 parts by mass, per part by mass of the enzyme-modified isoquercitrin.

[0117] (B-III-3-5) The composition for intraoral use or oral ingestion according to (B-III-3-1) or (B-III-3-2), which is in the form of a gel and contains a thickening polysaccharide at a ratio of 1 to 500 parts by mass, preferably 2 to 450 parts by mass, and more preferably 2.5 to 350 parts by mass, per part by mass of the enzyme-modified isoquercitrin.

[0118] (B-III-3-6) The composition for intraoral use or oral ingestion according to any one of (B-III-3-1) to (B-III-3-5), wherein the composition for intraoral use or oral ingestion is a processed cereal food or beverage and contains a thickening polysaccharide at a ratio of 0.01 to 3000 parts by mass, preferably 0.05 to 2000 parts by mass, and more preferably 0.1 to 1200 parts by mass, per part by mass of the enzyme-modified isoquercitrin.

[0119] (B-III-3-7) The composition for intraoral use or oral ingestion according to any one of (B-III-3-1) to (B-III-3-6), which is a food or beverage for intraoral use or oral ingestion or a pharmaceutical product.

[0120] (B-III-3-8) The composition for intraoral use or oral ingestion according to any one of (B-III-3-1) to (B-III-3-7), which is a food or beverage for intraoral use or oral ingestion or a pharmaceutical product in the form of a gel having at least one of the following physical properties (1) and (2) or in the form of a sol having the following physical property (3):

[0121] (1) Breaking strain: 0.3 to 0.8;

[0122] (2) Hardness: 500 to 500,000 N / m 2 ; and

[0123] (3) Viscosity: 0.006 to 0.6 Pa-s.

[0124] Advantages of the Invention

[0125] A person ingests or is administered the salivation agent of the present invention, which can promote salivation in the person. A person with reduced salivation function ingests or is administered the salivation agent, which can improve the reduction in salivation in the person. Furthermore, the promotion of salivation by the use of the salivation agent of the present invention can enhance the self-cleaning action in the oral cavity, and can also prevent various negative effects (e.g., dry mouth, unpleasant feeling in the oral cavity, taste disorder, halitosis, dental caries, periodontal disease, mucosal infection, and like oral cavity dysfunction; difficulty in conversation and phonation, etc.) caused by reduced salivation. Furthermore, the salivation agent of the present invention, which promotes salivation, can promote swallowing in a person with difficulty in swallowing due to reduced salivation.

[0126] Furthermore, since the salivation agent of the present invention uses enzyme-modified isoquercitrin having a history of use as a food as an active ingredient, the salivation agent is highly safe, and can be preferably used as a composition for intraoral use or oral ingestion (e.g., a drug product, a quasi-drug, a food and a beverage (including a functional food and beverage, and a health food and beverage)) for continuous use in the oral cavity or oral administration. The salivation agent of the present invention can be used as a drug product for intraoral use or oral administration, and can be preferably used as a functional food or beverage or a health food or beverage in a replacement drug product or a complementary and replacement drug product.

[0127] The additive for the composition for intraoral use or oral ingestion of the present invention can impart a salivation-promoting action, a swallowing-easy property, and / or a mastication-easy property to the composition for intraoral use or oral ingestion (e.g., a food or beverage or a drug product). Therefore, the additive can be preferably used for the preparation of a food or beverage or a drug product for intraoral use or oral administration, which is ingested or administered to a person with reduced salivation function, a person with reduced swallowing function, or a person with reduced mastication function. In particular, since the additive for the composition for intraoral use or oral ingestion of the present invention containing a thickening polysaccharide at a ratio of 0.2 to 500 parts by mass per 1 part by mass of enzyme-modified isoquercitrin hardly affects the palatability (taste, odor, etc.), the additive can be used for the preparation of a composition for intraoral use or oral ingestion without strict limitation on the amount to be added.

[0128] Further, the composition for use in the oral cavity or for oral ingestion of the present application, which contains an additive for a composition for use in the oral cavity or for oral ingestion, has a saliva secretion promoting effect, a property of being easy to swallow, and / or a property of being easy to chew; and can preferably be used as a food or beverage or a medicine for use in the oral cavity or for oral administration to be ingested or administered to a person having a reduced saliva secretion function, a person having a reduced swallowing function, or a person having a reduced chewing function.

[0129] According to the method of the present application, the use of a thickening polysaccharide together with the enzyme-modified isoquercitrin can enhance the saliva secretion promoting effect of the enzyme-modified isoquercitrin. Therefore, when a composition for oral ingestion containing a thickening polysaccharide in addition to the enzyme-modified isoquercitrin is ingested or administered to a subject having a reduced saliva secretion function, saliva secretion is promoted in the subject, thereby improving the reduction in saliva secretion. BRIEF DESCRIPTION OF DRAWINGS

[0130] Figure 1 is a graph showing the measurement results of the saliva secretion promoting effect in Experimental Example 1. The amount of saliva secreted is shown as a relative value, with the amount of saliva secreted by ingestion of water being set to 1 (the same applies to Figure 2 ).

[0131] Figure 2 is a graph showing the measurement results of the saliva secretion promoting effect in Experimental Example 2.

[0132] Figure 3 is a graph showing the saliva secretion promoting effect of the sol composition for use in the oral cavity or for oral ingestion in Experimental Example 4 (control sample 4 and test samples 4-1 to 4-5). The xanthan gum (XG) content (mass %) of each composition for use in the oral cavity or for oral ingestion is also shown on the abscissa. The amount of saliva secreted is shown as a relative value, with the amount of saliva secreted by ingestion of water being defined as 1.

[0133] Figure 4 is a graph showing the saliva secretion promoting effect of the sol composition for use in the oral cavity or for oral ingestion in Experimental Example 5 (test samples 5-1 to 5-5). The molar concentration (μM) of the enzyme-modified isoquercitrin content (content converted to rutin) in each composition for use in the oral cavity or for oral ingestion is also shown on the abscissa. The amount of saliva secreted is shown as a relative value, with the amount of saliva secreted by ingestion of water being defined as 1.

[0134] Figure 5 is a graph showing the saliva secretion promoting effect of the gel composition for use in the oral cavity or for oral ingestion in Experimental Example 6 (control samples 6-1 to 6-5 and test samples 6-1 to 6-5). The amount of saliva secreted is a relative value, with the amount of saliva secreted by ingestion of water being defined as 1.

[0135] Figure 6 Figure 7 is a graph showing the saliva secretion promoting effect of the gel composition for intraoral use or oral ingestion in Experimental Example 7 (control sample 7 and test samples 7-1 to 7-5). The molar concentration (μM) of the enzyme-modified isoquercitrin content (content converted into rutin) in each composition for intraoral use or oral ingestion is also shown on the abscissa. The amount of saliva secreted is a relative value, and the amount of saliva secreted by ingestion of water is defined as 1. DETAILED DESCRIPTION

[0136] (A-I) Sialogogue

[0137] (A-I-1) Enzymatically modified isoquercitrin

[0138] The saliva stimulant of the present application is characterized in that the stimulant contains enzymatically modified isoquercitrin as an active ingredient. The enzymatically modified isoquercitrin contains α-glucosyl isoquercitrin represented by the following formula as a main component, and is also referred to as transglycosylated isoquercitrin.

[0139]

[0140] In the above formula, n represents an integer of 0 to 10.

[0141] The α-glucosyl isoquercitrin contained in the enzymatically modified isoquercitrin can be a compound in which n is an integer of 0 to 10, or a mixture of two or more compounds in which n is an integer of 0 to 10. Preferably, the α-glucosyl isoquercitrin is a mixture, and more preferably a mixture of two or more compounds in which n is an integer of 0 to 6. The α-glucosyl isoquercitrin in which n is 0 is also referred to as isoquercitrin. In the present application, it is preferable to use the enzymatically modified isoquercitrin containing α-glucosyl isoquercitrin having a content converted into rutin of 60 mass% or more.

[0142] Since rutin and α-glucosyl isoquercitrin have the same molar extinction coefficient at a wavelength of 351 nm, and rutin is more easily available than α-glucosyl isoquercitrin, the α-glucosyl isoquercitrin content of the enzymatically modified isoquercitrin converted into rutin is shown. Therefore, in this technical field, it is a common practice to quantify the α-glucosyl isoquercitrin content of the enzymatically modified isoquercitrin converted into rutin by ultraviolet-visible absorption spectrometry using rutin as a standard sample.

[0143] Specifically, the α-glucosyl quercitrin content of the enzyme-modified quercitrin can be calculated as rutin by the following quantitative method described in the "enzyme-modified quercitrin" column in the Japanese Standards of Food Additives (Food Additive Codex), 8th edition (Ministry of Health, Labour and Welfare, Japan).

[0144] Quantification

[0145] (i) Dry the target enzyme-modified quercitrin (target sample) and accurately weigh about 0.05 g of the enzyme-modified quercitrin and dissolve in water so that the total volume is exactly 100 ml. If necessary, filtration can be performed. Accurately measure 4 ml of the solution and add a phosphoric acid solution (an aqueous solution prepared by dissolving 1 g of phosphoric acid in water so that the total volume is 1000 ml; also applicable hereinafter) so that the total volume is 100 ml, thereby preparing a test liquid.

[0146] (ii) In addition, rutin for quantification is dried at 135°C for 2 hours. Accurately weigh about 0.05 g of the rutin and dissolve in methanol so that the total volume is exactly 100 ml. Accurately measure 4 ml of the solution and add a phosphoric acid solution so that the total volume is exactly 100 ml, thereby preparing a standard liquid. (iii) Using the phosphoric acid solution as a control, the absorbance of the test liquid (At) and the standard liquid (As) at a wavelength of 351 nm is measured by UV-visible absorption spectrometry. The α-glucosyl quercitrin content converted to rutin is calculated by the following formula.

[0147] [mathematical formula 1]

[0148] α-glucosyl quercitrin content (as rutin (C 27 H 30 O 16 )) = (amount of rutin for quantification sampled (g) / amount of test sample sampled (g) x (At / As) x 100 (mass %))

[0149] Enzymatically modified isoquercitrin can generally be prepared by adding glucose to a mixture of isoquercitrin and starch or dextrin using a cyclodextrin glucosyltransferase. Isoquercitrin is generally obtained by enzymatic degradation of rutin. Isoquercitrin can also be obtained by other known methods (e.g., degradation of rutin, extraction separation of plants, and glycosylation of quercetin). Conveniently, a pharmaceutical preparation containing enzymatically modified isoquercitrin is commercially available. An example of such a commercially available product includes "San Emiq No. 1" produced by San-Ei Gen F.F.I., Inc. "San Emiq" is a registered trademark of San-Ei Gen F.F.I., Inc. The enzymatically modified isoquercitrin contained in "San Emiq No. 1" is a mixture of two or more compounds represented by the above formula (wherein n is selected from 0 to 6). San Emiq No. 1 contains α-glucosyl isoquercitrin in an amount of 60 mass% or more as a main component, converted into rutin. "San Emiq No. 1" contains α-glucosyl isoquercitrin in an amount of 10 mass% converted into rutin by the above quantitative method, and also contains dextrin as another component.

[0150] The salivation-promoting agent of the present application can be any promoting agent containing enzymatically modified isoquercitrin, as long as it provides a salivation-promoting effect. The content of enzymatically modified isoquercitrin is not particularly limited, and can be appropriately selected from the range of 0.001 to 0.5 mass% of α-glucosyl isoquercitrin (converted into rutin [C 27 H 30 O 16 ]) in the present specification. In the present specification, the content of enzymatically modified isoquercitrin is shown as the content of α-glucosyl isoquercitrin (converted into rutin [C 27 H 30 O 16 ]) in mass% unless otherwise specified. Therefore, in the present application (the present specification), "1 mass part of enzymatically modified isoquercitrin" means that the amount of α-glucosyl isoquercitrin contained in the enzymatically modified isoquercitrin is 1 mass part converted into rutin [C 27 H 30 O 16 ] in mass part.

[0151] (A-I-2) Thickening polysaccharide

[0152] The salivation-promoting agent of the present application can further contain a thickening polysaccharide in addition to the enzymatically modified isoquercitrin.

[0153] As shown in the experimental examples below, the salivation-promoting agent containing a thickening polysaccharide in addition to the enzymatically modified isoquercitrin can provide a higher salivation-promoting effect than the corresponding salivation-promoting agent not containing a thickening polysaccharide.

[0154] The thickening polysaccharide to be used in the present application is an edible thickening polysaccharide allowed to be used in a food or beverage or a pharmaceutical for oral administration. Examples of the thickening polysaccharide include xanthan gum, galactomannan (e.g., locust bean gum, guar gum, tara gum, etc.), deacylated gellan gum, highly acylated gellan gum, carrageenan (e.g., kappa-carrageenan, iota-carrageenan, lambda-carrageenan, etc.), tamarind gum, glucomannan, psyllium gum, synphorospongin gum (macrohomopssis gum), agar, gelatin, pectin (e.g., HM pectin, LM pectin, etc.), alginic acid, alginate (e.g., sodium alginate, potassium alginate, calcium alginate, etc.), pullulan, curdlan, tragacanth gum, ghatti gum, gum arabic, arabinogalactan, karaya gum, furcellaran, chitin, welan gum, cellulose (e.g., sodium carboxymethylcellulose, calcium carboxymethylcellulose, carboxymethylcellulose, hydroxypropylcellulose, hydroxypropylmethylcellulose, hydroxypropylethylcellulose, hydroxyethylcellulose, hydroxymethylcellulose, ethylcellulose, methylcellulose, fermented cellulose, crystalline cellulose, etc.), starches (e.g., starch, sodium carboxymethyl starch, carboxymethyl starch, hydroxypropyl starch, gelatinized starch, phosphoric acid cross-linked starch, octenylsuccinic acid starch, starch acetate, etc.), dextrin (e.g., polydextrose, indigestible dextrin, etc.), soybean polysaccharide, etc.

[0155] In the present application, among the thickening polysaccharides, at least one selected from the group consisting of xanthan gum, locust bean gum, guar gum, tara gum, deacylated gellan gum, highly acylated gellan gum, pectin, alginate, gelatin, agar, psyllium gum, and carrageenan is preferred. More preferably, the thickening polysaccharide is at least one selected from the group consisting of xanthan gum, locust bean gum, guar gum, deacylated gellan gum, highly acylated gellan gum, pectin, and carrageenan. Particularly preferably, the thickening polysaccharide is at least one selected from the group consisting of xanthan gum, pectin, and carrageenan. These thickening polysaccharides can be used alone or in combination of two or more. The combination of two or more thickening polysaccharides is not particularly limited. Examples include a combination of xanthan gum and guar gum; a combination of xanthan gum and locust bean gum; a combination of xanthan gum and carrageenan; a combination of xanthan gum, guar gum, and locust bean gum; and a combination of deacylated gellan gum and highly acylated gellan gum. In addition, at least one selected from these thickening polysaccharides can be used in combination with at least one selected from the above-described thickening polysaccharides.

[0156] The ratio of the thickening polysaccharide to the enzyme-modified isoquercitrin in the salivation agent of the present application can generally be selected from the range of 0.2 to 500 parts by mass per part by mass of the enzyme-modified isoquercitrin (converted into rutin; the same applies hereinafter). For example, when the salivation agent of the present application is in the form of a solid (e.g., a tablet, a granule, or a powder (powdered drug) or a dry syrup), the ratio of the thickening polysaccharide can be, for example, 0.2 to 500 parts by mass, preferably 0.3 to 400 parts by mass, and more preferably 0.4 to 350 parts by mass per part by mass of the enzyme-modified isoquercitrin. When the salivation agent of the present application is in the form of a paste, the ratio of the thickening polysaccharide can be, for example, 0.2 to 500 parts by mass, preferably 0.3 to 400 parts by mass, and more preferably 0.4 to 350 parts by mass per part by mass of the enzyme-modified isoquercitrin. When the salivation agent of the present application is in the form of a liquid, the ratio of the thickening polysaccharide can be, for example, 0.2 to 400 parts by mass, preferably 0.3 to 350 parts by mass, and more preferably 0.3 to 300 parts by mass per part by mass of the enzyme-modified isoquercitrin. When the salivation agent of the present application is in the form of a gel (jelly), the ratio of the thickening polysaccharide can be, for example, 1 to 500 parts by mass, preferably 2 to 450 parts by mass, and more preferably 2.5 to 350 parts by mass per part by mass of the enzyme-modified isoquercitrin.

[0157] As described above, the ratio of the thickening polysaccharide contained in the salivation agent of the present application varies depending on the form of the salivation agent. For example, when the form of the salivation agent is a solid form (e.g., a tablet, a chewable, a lozenge, a granule, a powder (powdered drug), a dry syrup, a film, or a stick preparation), the ratio of the thickening polysaccharide can be appropriately selected from the range of 1% by mass or more to 99.9% by mass or less. The ratio of the thickening polysaccharide is preferably 3 to 90% by mass, more preferably 5 to 80% by mass or more. When the form of the salivation agent is a paste or a liquid form (including a syrup, a health drink, a liquid, an emulsion, an oil, and a spray), the ratio of the thickening polysaccharide can be appropriately selected from the range of 0.02 to 30% by mass, preferably 0.02 to 10% by mass, and more preferably 0.02 to 8% by mass. When the salivation agent is in the form of a gel, the ratio of the thickening polysaccharide per part by mass of the enzyme-modified isoquercitrin can be appropriately selected from the range of 0.02 to 10% by mass. Preferably, the ratio of the thickening polysaccharide is 0.02 to 8% by mass, and more preferably 0.02 to 6% by mass.

[0158] (A-I-3) Other Components

[0159] In addition to the above-described components, the salivation agent of the present application can contain any edible component as long as the effect of the present application is not impaired.

[0160] Examples of the edible component include edible metal salts, excipients, organic acids, coloring agents, amino acids (e.g., glycine, arginine, lysine, alanine, glutamic acid, histidine, threonine, asparagine, aspartic acid, phenylalanine, leucine, valine, serine, tyrosine, isoleucine, methionine, etc.), nutrients including vitamins and minerals, antioxidants, preservatives, antibacterial agents, bacteriostatic agents, plant extracts (e.g., tea extract, coffee extract, cocoa extract, etc.), fruit juice (e.g., orange, grape, apple, peach, pineapple, tomato, strawberry, etc.), sweeteners (e.g., sugar such as sucrose, isosucrose, lactose, maltose, glucose, fructose, invert sugar, starch syrup, powdered starch syrup, reduced maltose syrup, honey, trehalose, palatinose (パラチノース), and D-xylose; sugar alcohols such as xylitol, sorbitol, maltitol, and erythritol; high-intensity sweeteners such as sodium saccharin, cyclamate or a salt thereof, potassium acesulfame, thaumatin, aspartame, chlorosucrose, alitame, neotame, stevia extract (e.g., stevioside), and momordica grosvenori extract (e.g., mogroside), flavorings, etc.

[0161] An edible metal salt is used to improve the solubility of the thickening polysaccharide in water, or to enhance the thickening and gelling functions. The kind of the edible metal salt is not particularly limited. Preferred examples include sodium salts (e.g., sodium chloride and sodium citrate), potassium salts (e.g., potassium chloride, potassium citrate, etc.), calcium salts (e.g., calcium chloride, calcium citrate, etc.), magnesium salts (e.g., magnesium chloride, etc.), and the like. When an edible metal salt is used, the proportion of the edible metal salt in the salivagogue of the present application can be, for example, 0.1 to 15 mass %, and preferably 0.5 to 10 mass %, regardless of the form of the salivagogue (solid, semi-solid, or liquid form).

[0162] In order to produce or stabilize the salivagogue for intraoral use or in a form for oral ingestion, various pharmaceutically acceptable carriers and additives for oral administration can be incorporated (see, for example, Pharmacopoeia, or "Japanese Pharmacopoeia Additives Dictionary" (published by Yakuji Nippo).

[0163] Examples of such carriers or additives include excipients such as monosaccharides (e.g., glucose, galactose, fructose, etc.), disaccharides (e.g., sucrose, white sugar, lactose, maltose, trehalose, etc.), sugar alcohols (e.g., xylitol, sorbitol, mannitol, etc.), oligosaccharides, starches (e.g., corn starch, partially gelatinized starch, etc.), starch hydrolysates (e.g., dextrin, powdered starch syrup, etc.), cellulose or cellulose derivatives (e.g., crystalline cellulose, low-substituted hydroxypropyl cellulose, sodium carboxymethyl cellulose, etc.), and talc; binders such as starch, gelatinized starch, gelatin, acacia, dextrin, methyl cellulose, ethyl cellulose, polyvinylpyrrolidone, hydroxypropyl methyl cellulose, hydroxypropyl cellulose, and carboxymethyl cellulose or salts thereof; disintegrants such as calcium carbonate, crospovidone, starch, carboxymethyl cellulose calcium, low-substituted hydroxypropyl cellulose, carboxymethyl starch, crystalline cellulose, and agar; lubricants such as magnesium stearate, talc, polyethylene glycol, and silicic anhydride; suspending agents such as polysorbate 80, polyoxyethylene hydrogenated castor oil, and pluronics; coating agents such as white sugar, talc, precipitated calcium carbonate, gelatin, acacia, pullulan, carnauba wax, and hydroxypropyl methylhydroxy-methy-lene glycol phthalate; flavoring agents such as white sugar, glucose, sodium saccharin, sorbitol, citric acid, and aspartame, etc. As long as the effects of the present application are not impaired, the following additives can also be used in addition to the above components: components generally acceptable as pharmaceutical additives, such as stabilizers, surfactants, plasticizers, capsule shells, solubilizers, reducing agents, buffers, sweeteners, bases, volatile aids, absorption promoters, adsorbents, synergists, solidifying agents, antioxidants, brighteners, fragrances, potency enhancers, coating agents, supports, extenders, wetting agents, moisture regulators, fillers, antifoaming agents, cooling agents, ingestion promoters, binders, enhancers, chewable agents, antistatic agents, coloring agents, sugar coatings, tonicity agents, softening agents, emulsifiers, combustible agents, binders, tackifiers, viscosity regulators, inflammation suppressors, heating agents, foaming agents, pH regulators, skin protectants, floatation agents, dispersants, propellants, aromatics, antirust agents, drying agents, release control membranes, preservatives, scavengers, preservatives, soothing agents, attractants, dissolving agents, dissolution aids, solvents, liners, release agents, and fluidizing agents; components acceptable as food additives, such as sweeteners, coloring agents, preservatives, thickening agents, gelling agents, starch binders, antioxidants, color-forming agents, bleaching agents, antifungal agents, emulsifiers, leavening agents, flavoring agents, sour agents, bitter agents, gloss agents, gum bases, nutritional fortifiers, and production aids; any components such as essences. Components having a salivation-promoting effect, such as spilanthol, can also be added.

[0164] (A-I-4) Form, preparation method, function, use, etc. of salivation agent

[0165] The salivating agent of the present invention is not limited in form, as long as it contains at least one enzyme-modified isoquercitrin, or an enzyme-modified isoquercitrin and a thickening polysaccharide. For example, the salivating agent may be in the form of a solid (e.g., tablets, chewable tablets, lozenges, pills, granules, powders (powdered drugs), dry syrups, films, sticks, etc.), a semi-solid (e.g., gels, pastes, etc.), or a liquid (e.g., syrups, health drinks, liquids, emulsions, oils, sprays, etc.).

[0166] There are no particular restrictions on whether salivating agents are in solid or semi-solid form, as long as they are for oral use (forms for intraoral application) or for oral administration (forms for oral administration). Salivating agents can be in the following forms, for example: tablets, chewable tablets, lozenges, pills, granules, powders (powdered drugs), dry syrups, films, sticks, gels, or pastes. When used, tablets, pills, granules, powders (powdered drugs), dry syrups, etc., can be added to drinking water, food, or beverages; and dissolved or dispersed and mixed therein, and then administered (ingested).

[0167] The salivating agent of the present invention can be prepared according to known methods. For example, the salivating agent in powder (powdered medicine) or dry syrup form can be prepared by mixing enzyme-modified isoquercitrin alone, or enzyme-modified isoquercitrin and thickening polysaccharide with excipient powder. Alternatively, the salivating agent in powder form can also be prepared by drying (e.g., spray drying, freeze drying, etc.) a liquid containing enzyme-modified isoquercitrin alone or enzyme-modified isoquercitrin and thickening polysaccharide. The salivating agent in granular form can be prepared by granulating the powder mixture. Alternatively, the salivating agent in granular form can also be prepared by spraying an aqueous solution of enzyme-modified isoquercitrin as a binder solution onto the powder thickening polysaccharide. The salivating agent in tablet form can be prepared by compressing the powder or granular salivating agent into tablets using a tablet press. Liquid salivator can be prepared by adding an enzyme-modified isoquercitrin alone or an enzyme-modified isoquercitrin and a thickening polysaccharide to a solvent (e.g., ethanol or water, or a mixture thereof, preferably water, such as purified water, deionized water, distilled water, or physiological saline); and preferably by further mixing (e.g., by stirring). The liquid salivator can be prepared into an emulsion or oil by further adding surfactants and / or dispersants and a lipid-soluble solvent (e.g., an oil solvent (e.g., a pharmaceutical oil solvent for dissolving lipid-soluble drugs, edible oil, etc.), and preferably by further mixing (e.g., by stirring) or homogenization using a high-pressure homogenizer, etc., during the preparation of the liquid salivator.

[0168] The gel salivating agent can be prepared by adding the enzyme-modified isoquercitrin and a thickening polysaccharide that contributes to gelation to a solvent (ethanol or water, or a mixture thereof, preferably purified water, ion-exchange water, or distilled water, or physiological saline), and heating until the thickening polysaccharide is uniformly dissolved (dispersed) (the heating temperature depends on the polysaccharide to be added, and can be, for example, 40 to 100°C), and then cooling. In this case, examples of the thickening polysaccharide that contributes to gelation include xanthan gum, locust bean gum, highly acylated gellan gum, gelatin, agar, and carrageenan. Alternatively, after the enzyme-modified isoquercitrin and the thickening polysaccharide that contributes to gelation are added to a solvent (ethanol or water, or a mixture thereof, preferably purified water, ion-exchange water, or distilled water, or physiological saline) and the resulting mixture is mixed and dissolved (dispersed) (at any appropriate temperature), the resulting solution can be gelled by adding an edible metal salt. In this case, examples of the thickening polysaccharide that contributes to gelation include deacylated gellan gum, pectin, alginate, and carrageenan. The edible metal salt is not particularly limited. Preferred examples of the edible metal salt include sodium salts (e.g., sodium chloride, sodium citrate, etc.), potassium salts (e.g., potassium chloride, potassium citrate, etc.), calcium salts (e.g., calcium chloride, calcium citrate, etc.), magnesium salts (e.g., magnesium chloride, etc.), and the like. When used, the edible metal salt is preferably incorporated in the composition for use in the oral cavity or for oral ingestion of the present application at a proportion of 0.00001 to 15 mass%, and preferably 0.00002 to 10 mass%.

[0169] When the salivating agent is in a liquid form, the viscosity can be adjusted to 6 mPa·s or more, preferably 6 to 600 mPa·s, if necessary, by using a thickening agent.

[0170] The viscosity herein refers to the viscosity measured using a fluid rheometer (e.g., ARES-LS1 manufactured by TA Instruments) under the following measurement conditions.

[0171] Measurement conditions

[0172] Measurement temperature: 20°C

[0173] Geometry: cone-plate (cone-plate), 50 mm in diameter, and a gap of 0.051 mm Shear rate: 100 s -1

[0174] The "viscosity" in the present specification means the viscosity measured under these conditions.

[0175] The thickening agent is not particularly limited. Examples include the thickening polysaccharides described above; monosaccharides such as glucose and fructose; disaccharides such as sucrose, lactose, and trehalose; oligosaccharides consisting of three or more monosaccharides linked together; polysaccharides such as starch, inulin, and polyglucose; starch syrup; sugar alcohols such as sorbitol, mannitol, maltitol, erythritol, lactitol, xylitol, and glycerol; and mixtures of sugars (e.g., molasses, honey, fructose-glucose liquid sugar, reduced maltose syrup, reduced starch hydrolysate, and starch syrup (these can be collectively referred to as "sugars")). These can be used alone or in combination of two or more. Preferably, the thickening agent is a thickening polysaccharide.

[0176] The saliva stimulants of the present application in liquid form can be provided in the form of a solution, a spray, a drop, or a jet (including compositions for intraoral use such as mouthwashes, liquid dentifrices, mouth rinses, and mouth sprays; and compositions for oral administration such as syrups), or formulated into health drinks. The saliva stimulants in various forms as described above can be used in a state contained in various containers such as bottles, pumps, sprayers, tubes, cans, and jars.

[0177] The stick-shaped preparation can be directly applied to the lips or the oral cavity, particularly to the tooth surface and the gums. The shape of the stick-shaped preparation is not particularly limited, as long as it is in a solid form that can be dissolved by saliva after application. Depending on the purpose of use, the preparation can form a cylinder, a square column, or the like. The stick-shaped preparation is preferably housed in a plastic container of a suitable shape that is easy to carry, in such a manner that the preparation can be pushed out. When used, an appropriate amount of the preparation can be pushed out from the housing container and applied to the lips or the oral cavity. Specifically, the preparation can form the same shape as a lipstick, a lip balm, or the like.

[0178] The pH of the saliva stimulants of the present application is not limited. Generally, the pH is preferably 3 to 9, more preferably 3.5 to 8, and still more preferably 3.5 to 7.5. It is generally preferable to adjust the saliva stimulants in solid or semi-solid form so that the pH of the saliva stimulants in the oral cavity after ingestion or application is 3 to 9. The pH in the oral cavity is preferably in the pH range of 3.5 to 8, and more preferably in the pH range of 3.5 to 7.5.

[0179] The saliva stimulants of the present application are preferably prepared in such a manner that the amount of enzyme-modified isoquercitrin ingested per time is 0.1 to 250 mg, and more preferably 0.4 to 100 mg. The saliva stimulants of the present application can be used at any time when the amount of saliva is reduced, or when it is desired to increase the secretion of saliva (at or before the oral cavity is dry). Thus, the number of times of daily application of the saliva stimulants of the present application is not particularly limited. The saliva stimulants containing the above-mentioned amount of enzyme-modified isoquercitrin can be applied once or several times a day, continuously or intermittently.

[0180] The sialogogue of the present application has a sialoagogue function or a sialoagogue enhancing function; and can be preferably used for a subject in which sialoagogue is reduced, or a subject who feels that sialoagogue is reduced. Examples of the subject in which sialoagogue is reduced include a patient who has hyposalivation or xerostomia; or a healthy person whose mouth is in a dry state, for example, at the time of exercise, bathing, or being awake.

[0181] (A-I-5) Food and beverage containing sialogogue

[0182] The food and beverage having a saliva secretion promoting effect can be produced by incorporating the salivation agent of the present application into the food or beverage. The timing of adding the salivation agent of the present application to the food or beverage is not particularly limited. For example, the salivation agent can be added in the step of producing the food or beverage, or immediately before consuming the food or beverage after production. The food or beverage into which the salivation agent of the present application is to be incorporated is not particularly limited. Examples include beverages such as milk beverages, lactic acid bacteria beverages, beverage yogurts, soft drinks, near-water beverages, isotonic beverages, carbonated beverages, juice beverages, vegetable beverages, fruit and vegetable beverages, alcoholic beverages, powdered beverages, concentrated beverages for dilution with water, coffee beverages, shiruko (sweet red bean soup with rice cake pieces) beverages, black tea beverages, green tea beverages, barley tea beverages, hojicha (roasted green tea) beverages, genmaicha (roasted brown rice) beverages, oolong tea beverages, yomogi (Japanese mugwort) tea beverages (hatomugi tea beverages), soba (buckwheat) tea beverages (soba tea beverages), fresh buckwheat (tartary buckwheat) tea beverages (tartary buckwheat tea beverages), pu-erh tea beverages, and smoothie beverages; puddings such as custard pudding, milk pudding, chocolate pudding, creme brulee pudding, and fruit juice-containing pudding; desserts such as sorbet, gummy candy, Bavarian cream, mousse, yogurt, and multi-layered dessert; frozen desserts such as ice cream, ice milk, water ice, milk ice cream, fruit juice-containing ice cream, soft serve ice cream, ice pops, sherbet, and ice confection; chewing gums (gum and gummy candy particles) such as chewing gum and bubble gum; chocolates such as marble chocolate and similar coated chocolate, strawberry chocolate, blueberry chocolate, melon chocolate, and similar flavored chocolate; ramune (tablet candy) (ramune gummy candy); hard candies (including small candies, butter balls, and marble sugar beans (marble)), soft candies (including caramel, toffee, gummy candy, and marshmallow), drop candy, toffee, and similar caramel, and the like; baked confections such as hard biscuit, cookie, macaroon, melonpan (deep-fried doughnut), mochi (rice cake) pieces, and pancake (thin crisp biscuit made of ordinary rice) (the above items are confections); soups such as miso soup, cheese soup (clear soup) (sashimi soup), clear broth, thick soup, and vegetable soup; pickles such as sunomono (lightly pickled vegetable), soy sauce pickles, salted vegetables, and miso pickles; sauces such as vinegar-based dressing, non-oil dressing, ketchup, gravy, and sauce; jams such as strawberry jam, blueberry jam, citrus jam, apple jam, apricot jam, and preserves; dessert sauces such as fruit sauce, syrup, and maple syrup; wine such as red wine; processed fruits such as candied cherry, apricot, apple, strawberry, and peach; processed meat such as ham, sausage, and roasted pork; ground seafood such as fish ham, fish sausage, ground fish, boiled fish paste, kamaboko (tubular fish cake), half pieces (patties of ground fish), satsuma-age (fried fish cake), ida-omaki (mixed fish paste omelet roll), and whale bacon;processed agricultural products such as konjac, adzuki beans, tofu (bean curd), and fermented soybeans (natto); dairy products such as butter, margarine, cheese, and whipped cream; noodles such as udon (noodles made from buckwheat), somen (thin wheat noodles), soba (thin wheat noodles), soba (noodles made from buckwheat), Chinese soba, spaghetti, macaroni, rice noodles, harusame (thin noodles made from bean starch), and ravioli; baked goods such as bread, sweet bread, side dish bread, rolls, French bread, bagels, and croissants; foods containing flour such as takoyaki (grilled dumplings with small pieces of octopus), okonomiyaki (grilled savory pancake with various ingredients), crepes, chikuwa (steamed fish dumplings), jiaozi (Chinese dumplings with minced pork and vegetable fillings), spring rolls, ravioli, and pizza; cakes such as large pancakes, pancakes, cheese cakes, chiffon cakes (shifon keiki), custard cakes, chocolate cakes, fruit cakes, egg tarts, pies, cream puffs, and muffins (muffin); Japanese sweets such as hagi mochi (Japanese rice cakes wrapped with sweet bean paste), jiaozi, warabi mochi, warabimochi (rice flour dumplings mixed with mugwort), kuzumochi (dumplings made from glutinous rice flour coated with sweetened red bean paste), steamed buns (with fillings), manju (red bean jellies), water manju (soft sweet bean paste), anko (dumplings made from glutinous rice flour coated with sweetened red bean paste), and mochi gashi (dumplings made from glutinous rice flour); staple foods such as cooked white rice, cooked brown rice, barley rice (rice cooked with barley), festival red rice, bamboo leaf dumplings, and rice cakes; and other various types of side dishes and processed foods such as mukaki (dried bread-like pieces of wheat gluten) and kamaboko (ground and seasoned fish). Foods and beverages to be incorporated into the salivation agents of the present application include concentrated liquid foods, enteral nutrients, thickened beverages, thickened liquid foods, nutritional supplement jellies, water supplement jellies, semi-solid liquid foods, liquid thickeners, and the like. A "liquid thickener" refers to a liquid preparation used by adding to a food or beverage before eating or drinking to thicken the food or beverage.

[0183] By promoting salivation and increasing the amount of saliva secreted, the salivation agents of the present application enable subjects with reduced salivation to easily swallow and chew. In this sense, the salivation agents of the present application can also be used as swallowing aids (swallowing improvers) or chewing aids (or chewing improvers). In the present application, "swallowing" or "swallow" refers to the act of swallowing an object in the mouth; "chewing" refers to the act of breaking up an intraoral composition in the mouth into small pieces, or thoroughly mixing an oral composition with saliva in the mouth while breaking up the composition into small pieces. As used herein, fine cutting includes not only biting an intraoral composition using the mandible and teeth, but also squeezing an oral composition using the gums or tongue.

[0184] (A-II) Process for the promotion of salivation in a subject

[0185] As described above, the salivation-promoting agent of the present application can promote salivation not only in healthy subjects, but also in subjects in which salivation is decreased or subjects who feel that salivation is decreased. Thus, the present application provides a method of producing salivation in such subjects.

[0186] The method can be performed by applying the salivation-promoting agent of the present application to the oral cavity of the subject, or by orally administering it. The application to the oral cavity can be appropriately selected depending on the form of the salivation-promoting agent. For example, when the salivation-promoting agent is in a liquid form (e.g., a solution, a spray, a drop, or a squirt), the application to the oral cavity can be, for example, rinsing the oral cavity, brushing the teeth, and gargling (gargling); or squirting into the mouth. When the salivation-promoting agent is in the form of a solid chewable agent (including chewing gum), the application can be, for example, chewing (chewing). For example, when the salivation-promoting agent is in the form of a stick, a gel, or a paste (cream, ointment), the application to the oral cavity can be performed using, for example, a swab. The oral administration can be performed by orally ingesting (administering) the salivation-promoting agent in a liquid, semi-solid, or solid form (e.g., a syrup, a health drink, a liquid, an emulsion, an oil, a spray, a gel, a paste, a tablet, a chewable agent, a lozenge, a pill, a granule, a powder (powdered agent), a dry syrup, a film, or a stick preparation; or a syrup, a drink, a candy, a jelly, a chewing gum, an edible film, etc.) according to the dosage form.

[0187] The timing of the ingestion (administration) is not particularly limited. The salivation-promoting agent can be administered at any time when or before the oral cavity is dry. The amount of the salivation-promoting agent to be used is also not particularly limited. It is preferred that the salivation-promoting agent be administered (ingested) in such an amount that the enzyme-modified isoquercitrin contained in the salivation-promoting agent is administered (ingested) in an amount of 0.1 to 250 mg, more preferably 0.4 to 100 mg. The number of times of administration (ingestion) of the salivation-promoting agent per day is not particularly limited. As described above, the salivation-promoting agent containing the enzyme-modified isoquercitrin can be administered (ingested) once a day or continuously or intermittently administered (ingested) several times a day in the above-mentioned amount.

[0188] The subject in which the method of the present application is preferably used includes, for example, a person suffering from hyposalivation or xerostomia; or a healthy person whose oral cavity is in a dry state at the time of exercise, bathing, or wakefulness, etc. Examples of the method for diagnosing decreased salivation include: (1) a method for measuring the amount of saliva produced at rest (spit method, cotton roll method), (2) a method for measuring the amount of saliva secreted after stimulation (Saxon method), (3) a method for measuring the degree of moisture of the oral mucosa (periotron flow index method, filter paper method, intraoral moisture meter), (4) a method for measuring the physical properties of saliva (viscosity test, spinnability test (thread drawing test)), and (5) a questionnaire method. Whether or not the salivation in the subject is decreased can be evaluated by using any one of these methods, or a combination of two or more of these methods.

[0189] (B-I) Additive for a composition for intraoral use or oral ingestion

[0190] The additive for a composition for intraoral use or oral ingestion (hereinafter also simply referred to as "additive of the present application") is characterized by comprising enzyme-modified isoquercitrin and a thickening polysaccharide.

[0191] (B-I-1) Enzyme-modified isoquercitrin

[0192] The enzyme-modified isoquercitrin for use in the present application is as described in (A-I-1) above, the disclosure of which is incorporated herein by reference in its entirety.

[0193] (B-I-2) Thickening polysaccharide

[0194] The thickening polysaccharide for use in the present application is an edible thickening polysaccharide approved for use in food and beverages or pharmaceutical products for oral administration. The thickening polysaccharide is as described in (A-I-2) above, the disclosure of which is incorporated herein by reference in its entirety.

[0195] The proportion of the thickening polysaccharide contained in the additive of the present application can vary depending on the form of the additive. For example, when the additive is in the form of a powder, granules or tablets, the proportion of the thickening polysaccharide can be suitably selected from 1 mass% or more and less than 100 mass%, preferably 3 to 90 mass%, and more preferably 5 to 80 mass%, as a rule. When the additive is in the form of a paste or a liquid, the proportion of the thickening polysaccharide can be suitably selected from 0.1 to 10 mass%, preferably 0.2 to 8 mass%, and more preferably 0.3 to 6 mass%, as a rule.

[0196] The ratio of the thickening polysaccharide to the enzyme-modified isoquercitrin in the additive of the present application can generally be selected from 0.2 to 500 parts by mass per part by mass of the enzyme-modified isoquercitrin (converted into rutin; the same applies hereinafter). The ratio of the thickening polysaccharide to the enzyme-modified isoquercitrin in the additive of the present application can be selected and adjusted depending on the form of the oral composition prepared by the addition. For example, when the additive of the present application is an additive for preparing a sol composition for oral ingestion, the ratio of the thickening polysaccharide can be 0.2 to 400 parts by mass, preferably 0.3 to 350 parts by mass, and more preferably 0.4 to 300 parts by mass per part by mass of the enzyme-modified isoquercitrin. When the additive of the present application is an additive for preparing a gel composition for oral administration, the ratio of the thickening polysaccharide is 1 to 500 parts by mass, preferably 2 to 450 parts by mass, and more preferably 2.5 to 350 parts by mass per part by mass of the enzyme-modified isoquercitrin. When the additive of the present application is an additive for preparing a food or beverage prepared by processing a cereal grain (processed cereal food or beverage), the ratio of the thickening polysaccharide can be, for example, 0.01 to 3000 parts by mass, preferably 0.05 to 2000 parts by mass, and more preferably 0.1 to 1200 parts by mass per part by mass of the enzyme-modified isoquercitrin.

[0197] (B-I-3) Other components

[0198] The additive of the present application can contain any edible component other than the above components, provided that the effects of the present application are not impaired.

[0199] Examples of the edible component include, but are not limited to, those mentioned in (B-I-3) above, the disclosure of which (including the disclosure regarding the ratio of the edible metal salt) is incorporated herein by reference in its entirety.

[0200] (B-I-4) Form, method of preparation, effects, uses, etc. of the additive

[0201] The form of the additive of the present application is not limited as long as the additive contains at least the enzyme-modified isoquercitrin and the thickening polysaccharide. For example, a solid form, a paste form, and a liquid form can be used. Preferably, the form of the additive is a solid form, such as a powder, a granule, or a tablet; or a liquid form. The additive is more preferably in the form of a granule because it has excellent solubility in water.

[0202] The present application additive can be prepared in a general manner according to the form. For example, the additive in powder form can be prepared by mixing the enzyme-modified isoquercitrin and thickening polysaccharide with excipient powder. Alternatively, the additive in powder form can also be prepared by drying (e.g., spray drying, freeze drying) a liquid containing the enzyme-modified isoquercitrin and thickening polysaccharide. The additive in granular form can be prepared by granulating the powder mixture. Alternatively, the additive in granular form can also be prepared by spraying the enzyme-modified isoquercitrin as a binder solution on the powder thickening polysaccharide. The additive in tablet form can be prepared by using a tablet machine to make tablets from the powdered or granular additive. The liquid additive can be prepared by adding the enzyme-modified isoquercitrin and thickening polysaccharide to a solvent (preferably water).

[0203] When water or a composition for intraoral use or oral ingestion containing water (e.g., a liquid composition for intraoral use or oral ingestion) is ingested or administered, the present application additive is generally used by adding to the target composition for intraoral use or oral ingestion. The target composition for intraoral use or oral ingestion is water itself, or is formulated in such a manner that the composition contains at least a predetermined amount of water. Therefore, when the present application additive is added and mixed by stirring, the viscosity increases so that the composition becomes a sol or a gel.

[0204] The temperature of the target composition for intraoral use or oral ingestion when the present application additive is added and mixed can be, for example, a temperature at which the present application additive is dissolved or dispersed and the thickening polysaccharide contained in the additive is thus hydrated and swelled. The temperature can vary depending on the type of thickening polysaccharide, and can be appropriately set to 1 to 100°C.

[0205] The amount of the present application additive added to the target composition for intraoral use or oral ingestion can be appropriately adjusted depending on the kind, water content, purpose, and use of the target composition for intraoral use or oral ingestion. For example, the additive is preferably added in such a proportion that the enzyme-modified isoquercitrin content of the composition for intraoral use or oral ingestion after the incorporation of the present application additive therein is 0.0005 to 1 mass%. The enzyme-modified isoquercitrin content of the composition for intraoral use or oral ingestion is preferably 0.001 to 0.7 mass%, and more preferably 0.0015 to 0.5 mass%.

[0206] When the target composition for intraoral use or oral ingestion is a food or beverage prepared by processing a cereal (processed cereal food or beverage), the additive is particularly preferably added in such a proportion that the enzyme-modified isoquercitrin content of the composition for intraoral use or oral ingestion after the incorporation of the present additive therein is 0.003 to 0.5 mass%. The enzyme-modified isoquercitrin content of the processed cereal food or beverage is preferably 0.005 to 0.45 mass%, and more preferably 0.0065 to 0.4 mass%.

[0207] The present additive can be used to impart a saliva secretion promoting effect to the target composition for intraoral use or oral ingestion. In other words, the present additive is used to prepare a composition for intraoral use or oral ingestion having a saliva secretion promoting effect. In this sense, the present additive can be referred to as a salivation agent. A "salivation agent" has an effect of increasing the amount of saliva secretion. In the present invention, as described above, a "salivation agent" imparts an effect of increasing the amount of saliva secretion (saliva secretion promoting effect) to a composition for intraoral use or oral ingestion.

[0208] The present additive can be used to impart a property of easy swallowing to the target composition for intraoral use or oral ingestion. In other words, the present additive is used to prepare a composition for intraoral use or oral ingestion that can be easily swallowed. In this sense, the present additive can be referred to as a swallowing aid (or swallowing improver). In addition, the present additive can be used to impart a property of easy mastication to the composition for intraoral use or oral ingestion. In other words, the present additive is used to prepare a composition for intraoral use or oral ingestion that can be easily masticated. In this sense, the present additive can be referred to as a mastication aid (or mastication improver).

[0209] The concepts or definitions of "swallowing" and "mastication" are as described above in (A-I-5), the disclosure of which is incorporated herein by reference in its entirety.

[0210] (B-I-5) Composition for intraoral use or oral ingestion to which the present additive is added

[0211] The composition for use in the oral cavity to which the additive of the present application is added is a food or beverage, or a medicine for use in the oral cavity, which is taken or ingested (administered) from the oral cavity or left in the oral cavity. Examples include foods and beverages such as chewing gums, chewing gums, films, and tablets (e.g., lozenges); and medicines for use in the oral cavity such as mouthwashes, toothpastes, films, tablets (e.g., lozenges). The target composition for oral ingestion to which the additive of the present application is added is a food or beverage or a medicine for oral administration to be taken or ingested (administered) from the oral cavity. The composition for use in the oral cavity and the composition for oral ingestion differ in that the composition for use in the oral cavity refers to a composition used in a state of being present in the oral cavity for a certain period of time (including a composition that is swallowed, as well as a composition that is not swallowed), while the composition for oral ingestion is generally swallowed without remaining in the mouth except for the time required for mastication. However, the composition for use in the oral cavity and the composition for oral ingestion are not necessarily strictly distinguished from each other, and can partially overlap. In order to distinguish from the composition for oral ingestion of the present application described later, the composition for use in the oral cavity or oral ingestion to which the additive of the present application is to be added can also be referred to as "target composition for use in the oral cavity or oral ingestion", and the food or beverage or medicine for use in the oral cavity or oral ingestion to which the additive of the present application is to be added is also referred to as "target food or beverage" and "target medicine for use in the oral cavity or oral ingestion"

[0212] Specific examples of the target food or beverage include beverages such as water (including mineral water), soft drinks (e.g., tea-based beverages, fruit beverages, vegetable beverages, coffee beverages, cocoa beverages, sports supplement beverages, carbonated beverages, lactic acid beverages, soy milk, soy milk beverages, isotonic beverages, and the like), dairy products (e.g., milk, lactic acid bacteria beverages, and the like); soup products such as soup, miso soup, mochi red bean soup (sweet red bean soup with rice cake), and amazake (sweet beverage made from fermented rice); confectionery products (including paste or gel confectionery, liquid confectionery products (e.g., crumb food, paste food, and weaning food)); nutritional supplement beverages and foods (including nutritional supplement beverages or foods in paste or gel form, liquid nutritional supplement beverages and foods (e.g., crumb food, paste food, and weaning food)); staple foods (including, for example, rice food, noodles, baked food, and the like, liquid staple foods (e.g., crumb food, paste food, and weaning food)); side dishes (including liquid side dishes (e.g., crumb food, paste food, and weaning food)); concentrated liquid foods; enteral nutrients (orally administered or orally ingested); and the like. The above-mentioned confectionery, nutritional supplement beverages and foods, staple foods, side dishes, and the like include processed cereal foods and beverages obtained by processing cereal grains. The crumb food herein refers to a food obtained by breaking food material with a cutter, a mixer, or the like. The paste food refers to a food obtained by forming a food material into a paste. There is no strict distinction between the crumb food and the paste food. Both are adjusted to have high flowability to allow people having difficulty in swallowing or mastication to easily eat. If necessary, the flowability of the crumb food and the paste food can be adjusted by adding water.

[0213] Examples of the processed cereal food include foods and beverages obtained by processing, for example, grains such as cereals (barley, wheat), Japanese millet, millet, rice, buckwheat, legumes (for example, soybeans), and corn. Examples include, but are not limited to, confectionery (for example, baked confectionery such as cookies, biscuits, crackers, donuts, bread sticks, cakes (including pancakes), Madeleines, macaroons, pies, and cream puffs), fried confectionery, and steamed confectionery); cooked rice products; noodles (for example, udon (noodles made of wheat flour), soba, ramen, chow mein (starch noodles), macaroni, and wontons); baked goods (including Chinese buns and pizza); wrapped foods (for example, gyoza (Chinese dumplings with minced pork and vegetable fillings), shumai (steamed meat dumplings), wontons, and spring rolls) and their wrappers; premix powders for producing flour-containing foods, such as pancake mixes, mixes for takoyaki (grilled dumplings with a small amount of octopus), mixes for okonomiyaki (grilled savory pancake with multiple ingredients), crepe mixes, batter mixes) (for example, pancake mixes, takoyaki mixes, okonomiyaki mixes, crepe mixes, and batter mixes), cornflakes, and the like. Many of these processed cereal foods or beverages have a low water content, tend to be dry, and are difficult to form into a bolus; and become sticky when water is added, thus being difficult to melt in the mouth or becoming difficult to swallow. In particular, many cooked rice foods, as well as confectionery, noodles, and baked goods that mainly contain flour have physical properties that make it difficult for people with reduced mastication function or reduced swallowing function to swallow. When the additive of the present application is applied to obtain processed foods and beverages having such physical properties, the mouth dissolvability of the processed cereal product can be improved. Furthermore, a sense of cohesion in the mouth and / or a sense of adhesion to the pharynx can be reduced when these foods are consumed. Thus, processed cereal foods and beverages that are easy to swallow can be prepared.

[0214] The target pharmaceutical product for use in the oral cavity or for oral ingestion is not particularly limited as long as it is for use in the oral cavity or for oral administration. Examples include powders (powdered pharmaceuticals), granules, tablets (including lozenges and chewable tablets), pills, capsules, films, and liquids (health drinks).

[0215] When the present additive is incorporated into a target composition for intraoral use or oral ingestion, the composition for intraoral use or oral ingestion preferably contains at least a predetermined amount of water. The water content of the target composition for intraoral use or oral ingestion is preferably 60% by mass or more, preferably 70% by mass or more, and more preferably 80% by mass or more. Therefore, when the water content of the target composition for intraoral use or oral ingestion (food and beverage for intraoral use or oral administration, pharmaceutical product) is less than 60% by mass, the water content of the composition for intraoral use or oral ingestion is preferably adjusted to the above range before the present additive is added. For example, when the target composition for intraoral use or oral ingestion is a pharmaceutical preparation in the form of a powder or granules, a method including adding water to achieve a water content of 60% by mass or more and dispersing such preparation in water can be used.

[0216] (B-II) Composition for intraoral use or oral ingestion and process for its production

[0217] The present application provides a composition for intraoral use or oral ingestion comprising enzyme-modified isoquercitrin and a thickening polysaccharide. The composition for intraoral use or oral ingestion includes a composition for intraoral use or oral ingestion containing the above-described present additive. The present composition for intraoral use is a food or beverage or a pharmaceutical product that is ingested or taken (administered) from the oral cavity and remains in the oral cavity. Examples include food and beverage such as chewing gum, film, and tablet; and pharmaceutical products for intraoral use such as mouthwash, toothpaste, film, and tablet. The present composition for oral administration is not limited as long as it is orally ingestible or administrable. Examples of the composition include food and beverage and pharmaceutical products for oral administration.

[0218] The present composition for intraoral use or oral ingestion can be prepared by using enzyme-modified isoquercitrin and a thickening polysaccharide, preferably using the above-described present additive.

[0219] The proportion of enzyme-modified isoquercitrin in the present composition for intraoral use or oral ingestion is not particularly limited as long as the effects of the present application are provided. The proportion can generally be, for example, 0.0005 to 1% by mass, preferably 0.001 to 0.7% by mass, and more preferably 0.0015 to 0.5% by mass. When the target composition for intraoral use or oral ingestion is a food or beverage prepared by processing grains (processed cereal food or beverage), the proportion of enzyme-modified isoquercitrin in the present oral composition is particularly preferably 0.003 to 0.5% by mass, more preferably 0.005 to 0.45% by mass, and even more preferably 0.0065 to 0.4% by mass.

[0220] The proportion of the thickening polysaccharide in the composition for intraoral use or oral ingestion of the present application can be, for example, 0.2 to 500 parts by mass per 1 part by mass of the enzyme-modified isoquercitrin contained in the composition for intraoral use or oral ingestion of the present application. The proportion of the thickening polysaccharide to the enzyme-modified isoquercitrin contained in the composition for intraoral use or oral ingestion of the present application can be selected and adjusted depending on the kind of the composition for intraoral use or oral ingestion to which the thickening polysaccharide is added. For example, when the composition for intraoral use or oral ingestion of the present application is a sol composition for intraoral use or oral ingestion, the proportion of the thickening polysaccharide can be, for example, 0.2 to 400 parts by mass, preferably 0.3 to 350 parts by mass, and more preferably 0.4 to 300 parts by mass, per 1 part by mass of the enzyme-modified isoquercitrin contained in the composition for intraoral use or oral ingestion. When the composition for intraoral use or oral ingestion of the present application is a gel composition for intraoral use or oral ingestion, the proportion of the thickening polysaccharide can be, for example, 1 to 500 parts by mass, preferably 2 to 450 parts by mass, and more preferably 2.5 to 350 parts by mass, per 1 part by mass of the enzyme-modified isoquercitrin contained in the composition for intraoral use or oral ingestion. When the composition for intraoral use or oral ingestion of the present application is a processed cereal food or beverage, the proportion of the thickening polysaccharide can be, for example, 0.01 to 3000 parts by mass, preferably 0.05 to 2000 parts by mass, and more preferably 0.1 to 12000 parts by mass, per 1 part by mass of the enzyme-modified isoquercitrin.

[0221] There is no particular limitation as long as the above conditions are satisfied. The proportion of the thickening polysaccharide is usually 0.01 to 10 parts by mass, preferably 0.02 to 8 parts by mass, and more preferably 0.03 to 6 parts by mass, per 100 parts by mass of the composition for intraoral use or oral ingestion of the present application.

[0222] The composition for intraoral use or oral ingestion of the present application can be prepared by adding the enzyme-modified isoquercitrin and the thickening polysaccharide to the target composition for intraoral use or oral ingestion of the present application before ingestion or administration (preferably, just before use). The composition for intraoral use or oral ingestion of the present application can be prepared by adding the enzyme-modified isoquercitrin and the thickening polysaccharide to the target composition for intraoral use or oral ingestion and stirring the mixture. After stirring the mixture, if necessary, the resulting product is allowed to stand or cool to solidify the product into a gel, thereby preparing the composition for intraoral use or oral ingestion of the present application. As the enzyme-modified isoquercitrin and the thickening polysaccharide, the above-described additives of the present application can be conveniently used.

[0223] The target composition for intraoral use or oral ingestion includes, for example, those disclosed in the above (B-I-5). The disclosure is incorporated herein by reference. When the water content of the target composition for intraoral use or oral ingestion is less than 60 mass%, it is preferable to adjust the water content of the target composition for intraoral use or oral ingestion to 60 mass% or more, for example, by adding water.

[0224] The temperature conditions for adding the enzyme-modified isoquercitrin and the thickening polysaccharide (or the additive of the present application) to the composition for intraoral use or oral ingestion or the temperature conditions for stirring mixing can be any temperature at which the enzyme-modified isoquercitrin and the thickening polysaccharide can be dissolved or dispersed in the target composition for intraoral use or oral ingestion.

[0225] Among the thickening polysaccharides, deacylated gellan gum, carrageenan, pectin, alginate, and the like have the property of increasing the viscosity or gelling in the presence of a soluble metal salt. Therefore, when such a thickening polysaccharide is used, it is preferable to use a soluble metal salt together. The soluble metal salt to be used is not limited, and preferred examples thereof include sodium salts (for example, sodium chloride, sodium citrate, and the like), potassium salts (for example, potassium chloride, potassium citrate, and the like), calcium salts (for example, calcium chloride, calcium citrate, and the like), magnesium salts (for example, magnesium chloride, and the like), and the like. When an edible metal salt is used, the preferable proportion of the edible metal salt in the composition for intraoral use or oral ingestion of the present application is generally 0.00001 to 15 mass%, preferably 0.00002 to 10 mass%.

[0226] The method of stirring mixing is not particularly limited. For example, mixing can be performed by stirring with a chopstick, spoon, or fork, or by using a stirring tool such as a household stirrer, a food processor, a rotary beater, a blender, a cooking cutter, or a propeller stirrer.

[0227] The composition for intraoral use or oral ingestion of the present application thus obtained can be prepared in the form of a gel or sol having predetermined physical properties.

[0228] The "gel" referred to herein specifically means that when the product is left standing for 1 to 2 minutes at a product temperature of 20°C, its shape is maintained, and the product does not flow under its own weight; that is, there is no change in its shape between the state after standing for 1 minute at a product temperature of 20°C and the state after standing for 2 minutes at 20°C. The "sol" means that when the product is left standing at a product temperature of 20°C, the product flows under its own weight, and its shape cannot be maintained; or there is a change in its shape between the state after standing for 1 minute at a product temperature of 20°C and the state after standing for 2 minutes at 20°C. These all refer to the state under standard atmospheric pressure (1 atm).

[0229] When the composition for intraoral use or oral ingestion of the present application is in the form of a gel, the composition for intraoral use or oral ingestion preferably has a breaking strain of 0.3 to 0.8, more preferably 0.4 to 0.8, and still more preferably 0.45 to 0.75, as determined under standard atmospheric pressure conditions at a product temperature of 20°C.

[0230] The "breaking strain" referred to herein can be determined by the following measurement method.

[0231] Method for determining the strain at break

[0232] (a) As a test sample, a composition for intraoral use or oral ingestion (test sample) in the form of a cylinder having a diameter of 20 mm and a height of 10 mm was prepared (product temperature: 20°C).

[0233] (b) The test sample was compressed using a texture analyzer (TA-XT-2i (manufactured by Stable Micro Systems) texture analyzer). Compression was performed at a rate of 10 mm / s using a jig having a diameter of 100 mm.

[0234] (c) The breaking point was determined from the "stress-strain curve" obtained by compression, and the breaking strain was calculated by the following equation.

[0235] [Equation 2]

[0236] Breaking strain = A / B.

[0237] A: Distance (mm) from the position at which the jig first contacted the test sample (upper surface of the test sample) to the point at which the sample was broken by contact with the jig and compression (breaking point).

[0238] B: Height of the test sample (= 10 mm)

[0239] When the breaking strain of the gel composition for intraoral use or oral ingestion is 0.3 to 0.8, preferably 0.4 to 0.8, and more preferably 0.45 to 0.75, the orally ingested composition that is broken up by mastication in the mouth is suitable for gathering into a mass (providing a sense of cohesiveness), thereby forming a bolus that can be easily masticated and swallowed even by a person with reduced mastication function or reduced swallowing function. If the breaking strain exceeds 0.8, it takes time to break up the orally ingested composition in the mouth, and swallowing difficulty can occur.

[0240] The gel composition for intraoral use or oral ingestion containing both the enzyme-modified isoquercitrin and the thickening polysaccharide tends to have a higher saliva secretion promoting effect because the gel composition for intraoral use or oral ingestion has a smaller breaking strain. Specifically, when the gel food or beverage (20°C) has a breaking strain of 0.3 to 0.8, preferably 0.4 to 0.8, and more preferably 0.45 to 0.75, a particularly remarkable saliva secretion promoting effect is provided.

[0241] When the composition for intraoral use or oral ingestion of the present application is in the form of a gel, the composition for intraoral use or oral ingestion preferably has a "hardness" of 500,000 N / m 2 or less, preferably 500 to 400,000 N / m 2 , and more preferably 500 to 250,000 N / m 2 , as measured under standard atmospheric conditions at a product temperature of 20°C. The "hardness" can be determined in accordance with the Universal Design Food Self-Regulation Standards, Second Edition (Japan Nutrition and Food Association (Japan Nutrition and Food Association)). More specifically, the hardness can be determined by the following measurement method.

[0242] Method for measuring hardness

[0243] The test sample is placed in a container having a diameter of 40 mm and a height of 20 mm. Using a texture analyzer (TA-XT-2i (manufactured by Stable Micro Systems) texture analyzer) and a resin plunger having a diameter of 20 mm and a height of 8 mm, compression measurement is performed twice at a compression speed of 10 mm / sec and a gap of 5 mm. The maximum stress at the first compression is defined as the "hardness" (N / m 2 ).

[0244] In particular, when the "hardness" is 500 to 500,000 N / m 2 , preferably 500 to 250,000 N / m 2 , the obtained oral composition is easy to chew or swallow even for a person with reduced mastication function.

[0245] When the composition for intraoral use or oral ingestion of the present application is in the form of a sol, the composition for intraoral use or oral ingestion has a viscosity of 0.006 Pa-s or more, more preferably 0.006 to 0.6 Pa-s, and still more preferably 0.008 to 0.4 Pa-s at a shear rate of 100 s -1 . The "viscosity" referred to herein can be measured by using a clamp having a cone-plate geometry with a diameter of 50 mm (made of resin) and at a sample measurement temperature (product temperature) of 20°C and a shear rate of 100 s-1 The viscosity values were read at a shear rate of 0.1 sec"1. An ARES-LSl (manufactured by TA Instruments) was used as the measuring device.

[0246] As shown in the experimental examples described below, the composition for intraoral use or oral ingestion obtained by containing the thickening polysaccharide in addition to the enzyme-modified isoquercitrin has an excellent saliva secretion promoting function compared to the composition for intraoral use or oral ingestion not containing the thickening polysaccharide. Therefore, the composition for intraoral use or oral ingestion can be provided as a food or beverage or a pharmaceutical for intraoral use or oral administration suitable for a person having a reduced saliva secretion function. The composition for intraoral use or oral ingestion of the present application containing the thickening polysaccharide in addition to the enzyme-modified isoquercitrin has an excellent swallowability and chewability compared to the composition for intraoral use or oral ingestion not containing the thickening polysaccharide. Therefore, the composition for intraoral use or oral ingestion of the present application can be provided as a food or beverage which can be properly ingested by a person having a reduced mastication function and / or a person having a reduced swallowing function, or as a pharmaceutical for intraoral use or oral administration which can be properly taken by a person having a reduced mastication function and / or a person having a reduced swallowing function.

[0247] When the composition for intraoral use or oral ingestion of the present application is a processed cereal food or beverage, the timing of adding the composition is not particularly limited as long as the composition contains the enzyme-modified isoquercitrin and the thickening polysaccharide before ingestion or administration (taking). For example, when the composition for intraoral use or oral ingestion of the present application is a baked confectionery product (e.g., a cookie), the enzyme-modified isoquercitrin and the thickening polysaccharide can be added to the dough before baking to provide a processed cereal food or beverage having an improved mouth dissolving feeling.

[0248] Examples

[0249] The following experimental examples and formula examples are provided to better illustrate the constitution and effects of the present application. However, the present application is in no way limited by these experimental examples and the like.

[0250] Experimental Example 1

[0251] (1) Preparation of a test sample

[0252] A preparation of enzyme-modified isoquercitrin (SAN No. 1: produced by San-Ei Gen FFI) (containing enzyme-modified isoquercitrin at a ratio of 10 mass% of α-glucosyl isoquercitrin (converted into rutin) and also containing dextrin as another component); α-glucosyl rutin (αG Rutin) (produced by Toyo Sugar Refining Co., Ltd.); and quercetin (produced by LKT Laboratories, Inc.) as test substances. These test substances were respectively dissolved in ion exchange water to prepare aqueous solutions (test samples) of the test substances at various concentrations shown in Table 1.

[0253] Table 1 shows, in addition to the content (mass%) of the test substance of each test sample, the content (molar concentration) of enzyme-modified isoquercitrin preparation and αG Rutin converted into rutin and the molar concentration of quercetin.

[0254] Table 1

[0255]

[0256] The molar concentration of quercetin and the content of rutin contained in enzyme-modified isoquercitrin and αG Rutin (both are quercetin glycosides) were calculated by the following method.

[0257] Quantification of quercetin (molar concentration)

[0258] The amount (molar concentration) of quercetin was calculated using the molecular weight of quercetin defined as 302.

[0259] Quantification of enzyme-modified isoquercitrin and aG rutin into rutin (molar concentration)

[0260] The amount (molar concentration) of enzyme-modified isoquercitrin and αG Rutin was determined according to the quantitative method described in the page of "enzyme-modified isoquercitrin" in the Food Additive Standards, 8th edition (Ministry of Health, Labour and Welfare, Japan). Details are as described above.

[0261] For example, when the α-glucosyl isoquercitrin content (converted into rutin (C 27 H 30 O 16 ) of enzyme-modified isoquercitrin preparation (sample A) calculated by the above formula [Mathematical formula 1] is 10 mass%, 6100 g of enzyme-modified isoquercitrin preparation (sample A) (610 x (100 / 10) = 6100) (610 is the molecular weight of rutin) corresponds to 1 mol of enzyme-modified isoquercitrin. Therefore, in the above case, for example, in order to achieve a molar concentration of 75 μM (75 x 10 -6 mol / L) of enzyme-modified isoquercitrin in an aqueous solution, it is necessary to dissolve (or disperse) 0.4575 g (6100 g / mol x 75 x 10 -6 mol) of enzyme-modified isoquercitrin preparation (sample A) in 1 L of water.

[0262] (2) Evaluation of saliva secretion promoting effect

[0263] Using 3 healthy persons (male, average age: 31.3 years old) as panelists, the saliva secretion promoting effect of the test samples prepared above was evaluated. Persons having relatively similar circadian variation of saliva secretion were selected from candidates as panelists.

[0264] Each test was evaluated using 15 g of each test sample according to the following method. As a blank, a test was performed in the same manner using 15 g of water instead of the test sample.

[0265] (i) After putting 15 g of each sample into the mouth and keeping it for 5 seconds, the sample was swallowed at once.

[0266] (ii) After 5 seconds, absorbent cotton (37.5 mm x 37.5 mm x 4 mm) was placed under the tongue (dorsal side) and kept for 2 minutes.

[0267] (iii) The absorbent cotton was taken out from under the tongue and the weight of the cotton (g) was measured. The weight was compared with the weight of the absorbent cotton before being put into the mouth to calculate the weight difference.

[0268] Each panelist performed the above test twice using the same test sample, and the average value was calculated. Based on the average value of each panelist, the average value and the standard deviation of all panelists were calculated.

[0269] (3) Evaluation results

[0270] Table 2 and Figure 1 The evaluation results (average value of 3 panelists) are shown. The results are shown as values (relative values) normalized by setting the amount of saliva secretion obtained using the blank (water) as 1.

[0271] Table 2

[0272]

[0273] From this result, it is clear that enzyme-modified isoquercitrin at a concentration of 25 to 750 μM exhibited saliva secretion promotion (increase) in a molar-dependent manner. In particular, the effect was provided upon putting enzyme-modified isoquercitrin into the mouth or immediately after swallowing enzyme-modified isoquercitrin. Such an effect was not observed in quercetin itself or aG rutin, which is also a quercetin glycoside like enzyme-modified isoquercitrin; the effect was specific to enzyme-modified isoquercitrin.

[0274] The above results clearly indicate that oral ingestion of a sample containing enzyme-modified isoquercitrin (intraoral use, oral ingestion) can significantly increase saliva secretion.

[0275] Experimental Example 2

[0276] Xanthan gum was added as a thickening polysaccharide to the test samples (aqueous solutions of enzyme-modified isoquercitrin, aG rutin, and quercetin) of Experimental Example 1 to thicken the samples. The saliva secretion promoting effects of the resulting compositions were evaluated in the same manner as in Experimental Example 1 to investigate whether or not the presence or absence of xanthan gum (thickened or not thickened) made a difference.

[0277] (1) Preparation of Test Samples

[0278] The test substances (enzyme-modified isoquercitrin preparation, aG rutin, and quercetin) were dissolved in drinking water and adjusted so that the rutin content (molar concentration) of each compound structure would be 150 μM (see Table 1). In addition, xanthan gum was added to the aqueous solutions so that the content would be 0.1 mass%, thereby thickening the solutions. For comparison, aqueous solutions (aqueous enzyme-modified isoquercitrin solution, aqueous aG rutin solution, aqueous quercetin solution) having a concentration of 150 μM (converted to rutin) without xanthan gum were prepared in the same manner as in Experimental Example 1.

[0279] The viscosity of each sample was measured using a fluid rheometer (ARES-LS1, manufactured by TA Instrument) under the following measurement conditions.

[0280] Measurement Conditions

[0281] Measurement temperature: 20°C

[0282] Geometry: cone-plate, 50 mm in diameter and 0.05 mm in gap

[0283] Shear rate: 100 s -1 .

[0284] (2) Evaluation of Saliva Secretion Promoting Effects and Results Thereof

[0285] The saliva secretion promoting effects of each of the test samples prepared above were evaluated in the same manner as in Experimental Example 1 (the same panel members were also used). Table 3 and Figure 2 The evaluation results (average values of 3 panel members) are shown.

[0286] The viscosity of all the thickened samples was 20 mPa-s, and the viscosity of all the non-thickened samples was 1 mPa-s (at 20°C).

[0287] Table 3

[0288]

[0289] These results clearly demonstrate that enzyme-modified isoquercitrin, through the incorporation of thickening polysaccharides, enhances the salivation-promoting effect (salivation-enhancing effect) of enzyme-modified isoquercitrin. On the other hand, this enhancement of the salivation-promoting effect (salivation-enhancing effect) through the incorporation of thickening polysaccharides was not observed in quercetin itself or in αG-rutin, which, like enzyme-modified isoquercitrin, is a quercetin glycoside; therefore, this effect is found to be specific to enzyme-modified isoquercitrin.

[0290] The results of Experimental Examples 1 and 2 above indicate that when a composition for oral use or for oral ingestion, containing enzyme-modified isoquercitrin and thickened by further incorporation of thickening polysaccharides, is ingested orally as a salivation stimulant, saliva production is significantly increased. The results also indicate that the additives to the compositions for oral use or for oral ingestion according to the present invention are suitable as additives for preparing thickening compositions for oral use or oral ingestion, or as swallowing aids.

[0291] Experimental Example 3

[0292] (1) Preparation of the test sample

[0293] The various material powders shown in Table 4 were mixed and compressed using a benchtop tablet press (manufactured by Ichihashi Seiki Co., Ltd.) at a compression pressure of 5 kN to prepare tablets containing enzyme-modified isoquercitrin, each weighing 1.5 g (tablet size: 18 mm φ).

[0294] (2) Evaluation and results of the effect of promoting salivation secretion

[0295] The salivation-promoting effect of each test sample prepared above was evaluated in the same manner as in Experimental Example 1 (with the same panel members).

[0296] Table 4

[0297] (quality%)

[0298]

[0299] *High-sweetness sweetener formulations: "San SA-8020 (containing 24% by weight of trichlorogalactose, 18% by weight of acesulfame potassium and 58% by weight of reduced paraglucose) is manufactured by San-Ei Gen FFI, Inc.

[0300] **Enzyme-modified isoquercitrin preparations: San No. 1 (containing 10% by mass α-glucosyl isoquercitrin (converted to rutin) and also containing dextrin as another component), produced by San-Ei Gen FFI Inc.

[0301] (3) Evaluation Results

[0302] Saliva secretion was evaluated by setting the amount obtained using a blank (water) sample as 1, displaying the average of the three group members as a standardized value, and then subtracting the amount of saliva secretion obtained in the comparative example (relative to water standardization) from the amount of saliva secretion obtained in the examples. The value obtained was 1.52. Compared with the administration or ingestion of tablets containing isoquercitrin without enzyme modification, the administration or ingestion of tablets containing enzyme modification significantly increased the amount of saliva secretion.

[0303] Example 4: Salivation-promoting effect of a sol composition for intraoral use or oral ingestion (No. 1)

[0304] (1) Preparation of the test sample

[0305] Additives to compositions for oral use or oral ingestion, containing enzyme-modified isoquercitrin and thickening polysaccharides in the proportions shown in Table 1, were dissolved in water (20°C) to prepare sol compositions for oral use or oral ingestion (test samples 4-1 to 4-5). Viscosity (shear rate: 100 s⁻¹) was measured at the product temperature of 20°C under standard atmospheric pressure. -1 As a control, enzyme-modified isoquercitrin was dissolved in water (20°C) in the proportions shown in Table 5 to prepare a composition for intraoral or oral use (control sample 4). Viscosity (shear rate: 100 s⁻¹) was measured at the product temperature of 20°C under standard atmospheric pressure. -1 Xanthan gum (produced by San-Ei Gen FFI, Inc.) is used as a thickening polysaccharide. The enzyme-modified isoquercitrin formulation "SAN" produced by San-Ei Gen FFI, Inc. is also used. No. 1” is an enzyme-modified isoquercitrin. Enzyme-modified isoquercitrin tablets contain α-glucosyl isoquercitrin (as rutin [C]). 27 H 30 O 16 It contains 10% by mass of enzyme-modified isoquercitrin and also contains dextrin as another component.

[0306] Under standard atmospheric pressure and sample temperature of 20°C, the ARES-LS1 fluid rheometer was used to measure the control sample and the test sample at 100 s. -1(produced by TA Instruments) at a shear rate of 0.1 sec"1.

[0307] Table 5

[0308] (mass %)

[0309]

[0310] * Enzymatically modified isoquercitrin preparation: "San No. 1" produced by San-Ei Gen F.F.I., Inc.

[0311] ** Proportion of α-glucosyl isoquercitrin (converted to rutin) in the sample (100 mass %) (mass %)

[0312] The content of the enzymatically modified isoquercitrin contained in the control sample 4 and the test samples 4-1 to 4-5 was adjusted so that the content of α-glucosyl isoquercitrin was 150 μM (converted to rutin). The content of the enzymatically modified isoquercitrin converted to rutin can be determined according to the quantitative method described in the page of "Enzymatically modified isoquercitrin" in the above-mentioned Japanese Standards of Food Additives, 8th edition (Ministry of Health, Labour and Welfare, Japan). For example, when the content of α-glucosyl isoquercitrin (as rutin (C 27 H 30 O 16 ) of the enzymatically modified isoquercitrin preparation (sample A) is 10 mass %, 6100 g (610 x (100 / 10) = 6100) of the enzymatically modified isoquercitrin preparation (sample A) (610 is the molecular weight of rutin) corresponds to 1 mol of the enzymatically modified isoquercitrin. Therefore, in the above case, in order to achieve a molar concentration of 150 μM (150 x 10 -6 mol / L) of the enzymatically modified isoquercitrin in an aqueous solution, it is necessary to dissolve (or disperse) 0.915 g (6100 g / mol x 150 x 10 -6 mol) of the enzymatically modified isoquercitrin preparation (sample A) in 1 L of water.

[0313] (2) Measurement of the salivation-promoting effect

[0314] Using three healthy subjects (subjects A to C: average age: 31.3 years old) who had no salivation abnormality in the 3rd position as a panel, the salivation promoting effects of the compositions for intraoral use or oral ingestion (control sample 4 and test samples 4-1 to 4-5) and water at 20°C (blank) were evaluated by the following method

[0315] (a) After 15 g of each sample (blank (water), control sample 4 or test samples 4-1 to 4-5) was placed in the mouth and held for 5 seconds, and then swallowed at one time.

[0316] (b) After swallowing and after 5 seconds, a size of 3.75 cm x 3.75 cm of absorbent cotton was placed under the tongue and held for 2 minutes. The weight of the absorbent cotton was measured in advance.

[0317] (c) After 2 minutes, the absorbent cotton was recovered and the weight was measured.

[0318] (d) From the change in the weight of the absorbent cotton before and after being placed under the tongue, the amount of saliva secretion by ingestion of each sample (blank (water), control sample 4 or test samples 4-1 to 4-5) was calculated.

[0319] Table 6 and Figure 3 The results are shown. In order to eliminate individual differences in the amount of saliva secretion, Table 6 and Figure 3 The values normalized by setting the average of the amount of saliva secretion in each subject determined by using water (blank) to 1 (relative value) are shown.

[0320] Table 6

[0321]

[0322] * The average of the amount of saliva secretion is a relative value in which the amount of saliva secretion (average) obtained by ingestion of the blank (water) is set to 1.

[0323] As shown in Table 6, when the composition for intraoral use or oral ingestion containing the additive containing the enzyme-modified isoquercitrin and the thickening polysaccharide (xanthan gum was used in this experiment) used for the composition for intraoral use or oral ingestion (test samples 4-1 to 4-5) was ingested, the amount of saliva secretion in all subjects was increased compared to ingestion of the blank (water). These compositions for intraoral use or oral ingestion had no taste or odor. Therefore, it is expected that when the additive for oral composition used for preparation of the above-described test samples 4-1 to 4-5 (Examples 4-1 to 4-5) is used, saliva secretion promotion can be imparted to the composition for intraoral use or oral ingestion without adversely affecting the flavor of the composition for intraoral use or oral ingestion to which the additive is applied.

[0324] Control sample 4, which did not contain a thickening polysaccharide, increased the amount of saliva secretion compared to water (blank). However, the increase in the amount of saliva secretion achieved by control sample 4 was smaller compared to that achieved by test samples 4-1 to 4-5, and control sample 4 showed a lower saliva secretion promotion effect.

[0325] The above results show that the thickening polysaccharide (xanthan gum) itself does not have saliva secretion promoting action when used alone. However, when the thickening polysaccharide is used together with the enzyme-modified isoquercitrin, the saliva secretion promoting action of the enzyme-modified isoquercitrin is enhanced.

[0326] Example 5: Evaluation of the salivation-promoting effect of a sol composition for intraoral use or oral ingestion (No. 2)

[0327] (1) Preparation of Test Samples

[0328] An additive for an intraorally used or orally ingested composition containing enzyme-modified isoquercitrin and a thickening polysaccharide at the proportions shown in Table 7 was dissolved in water (20°C) to prepare a sol composition for intraorally use or oral ingestion (test samples 5-1 to 5-5). Xanthan gum (produced by San-Ei Gen F.F.I., Inc.) was used as the thickening polysaccharide. An enzyme-modified isoquercitrin preparation "SAN No. 1" produced by San-Ei Gen F.F.I., Inc. was used as the enzyme-modified isoquercitrin.

[0329] Table 7

[0330] (mass %)

[0331]

[0332] * Enzyme-modified isoquercitrin preparation: "San No. 1" produced by San-Ei Gen F.F.I., Inc.

[0333] ** Proportion of α-glucosyl isoquercitrin (converted to rutin) in the sample (100 mass %) (mass %)

[0334] (2) Measurement of the salivation-promoting effect

[0335] Three healthy subjects (subjects A to C: average age: 31.3 years old) who had no saliva secretion abnormality in the 3rd position were used as panelists, and the saliva secretion promoting action of the intraorally used or orally ingested compositions (test samples 5-1 to 5-5) and water (blank) (all 20°C) was evaluated in the same manner as in Experimental Example 4.

[0336] Table 8 and Figure 4 The results are shown. In order to eliminate individual differences in the amount of saliva secretion, Table 8 and Figure 4 The values (relative values) normalized by setting the average of the amount of saliva secretion in each subject determined by using water (blank) to 1 are shown.

[0337] Table 8

[0338]

[0339] The average value of the saliva secretion amount is a relative value in which the saliva secretion amount (average value) obtained by ingesting a blank (water) is set to 1.

[0340] As shown in Table 8, the compositions for intraoral use or oral ingestion (test samples 5-1 to 5-5) ingesting the additives of the compositions for intraoral use or oral ingestion containing both the enzyme-modified isoquercitrin and the thickening polysaccharide (xanthan gum) increased the saliva secretion amount in all subjects compared to ingesting a blank (water); and saliva secretion promotion was observed. These compositions for intraoral use or oral ingestion had no taste or odor. Therefore, it is expected that incorporating the test samples 5-1 to 5-5 (additives of the compositions for oral ingestion) into the compositions for intraoral use or oral ingestion imparts saliva secretion promotion to the compositions for intraoral use or oral ingestion.

[0341] The above results indicate that when the thickening polysaccharide (xanthan gum) is used together with the enzyme-modified isoquercitrin, the saliva secretion promotion of the enzyme-modified isoquercitrin is improved in a manner depending on the content of the enzyme-modified isoquercitrin used.

[0342] Example 6: Salivation-promoting effect of a gel composition for intraoral use or oral ingestion (No. 1)

[0343] The additives of the compositions for intraoral use or oral ingestion containing the enzyme-modified isoquercitrin and the thickening polysaccharide in the proportions shown in Table 9 were dissolved in water (20°C) to prepare a gel composition for intraoral use or oral ingestion, and the saliva secretion promotion thereof was evaluated.

[0344] (1) Preparation of control sample and test sample

[0345] The gel composition for intraoral use or oral ingestion was prepared according to the following procedure.

[0346] 1. Among the components shown in Table 9, components (1) to (4) were mixed.

[0347] 2. The resulting powder mixture was added to ion-exchanged water (6), heated to 90°C, and dissolved for 10 minutes with stirring at 1300 rpm.

[0348] 3. Component (5) was added to the aqueous solution of components (1) to (4), and if necessary, the weight was corrected with ion-exchanged water (6).

[0349] 4. The aqueous solution of (1) to (6) was placed in a resin container having a multilayer structure containing an oxygen barrier layer (Lamicon cup, produced by Toyo Kan Co., Ltd.), and the container was sealed.

[0350] 5. The solution was sterilized (85°C, 30 minutes).

[0351] 6. The container was cooled to 8°C to gel the solution, thereby obtaining a gel composition for intraoral use or oral ingestion.

[0352] 7. The composition was stored in a 5°C refrigerator.

[0353] Table 9

[0354] (mass%)

[0355]

[0356] * Enzyme-modified isoquercitrin preparation: "San No. 1" (containing 10 mass% enzyme-modified isoquercitrin (converted to rutin), and also containing dextrin as another component), produced by San-Ei Gen F.F.I. Inc.

[0357] ** Proportion of α-glucosyl isoquercitrin (converted to rutin) in the test sample (100 mass%) (mass%)

[0358] Test samples 6-1 to 6-5 contained enzyme-modified isoquercitrin at a molar concentration (converted to rutin) of 150 μM as α-glucosyl isoquercitrin.

[0359] (2) Measurement of breaking strain and hardness of control samples and test samples (compositions for intraoral use or oral ingestion)

[0360] (2-1) Measurement of breaking strain

[0361] An aqueous solution of the components (1) to (6) of the control samples and test samples shown in Table 9 was poured into a glass tubular container (inner diameter: 20 mm, height: 10 mm, thickness: 1.5 mm), and cooled in an 8°C water tank for 2 hours to solidify the solution. The container was then left to stand at 5°C for 15 hours to prepare a gel composition for intraoral use or oral ingestion having a cylindrical shape (diameter: 20 mm, height: 10 mm) (control samples 6-1 to 6-5 and test samples 6-1 to 6-5).

[0362] The breaking strain of the gel composition for intraoral use or oral ingestion having a cylindrical shape (diameter: 20 mm, height: 10 mm) prepared above was measured using a texture analyzer (TA-XT-2i (produced by Stable Micro Systems) texture analyzer, probe: P / 50 (φ 50 mm)) according to the following described operation. For the measurement, the control sample or test sample was adjusted to a product temperature of 20°C.

[0363] (a) Using a jig with a diameter of 100 mm, the control sample or the test sample was compressed at a rate of 10 mm / s (initial position: 20 mm, gap: 1 mm).

[0364] (b) The yield point of the "load-strain curve" obtained by compression (point at which the stress rise slows: peak or inflection point) was defined as the breaking point. The breaking point of the control sample and the test sample was determined according to the following formula.

[0365] [mathematical formula 3]

[0366] Breaking strain = A / B.

[0367] A: Distance (mm) from the point at which the jig first comes into contact with the test sample (upper surface of the test sample) to the point at which the sample is broken by compression with the jig (breaking point).

[0368] B: Height of the test sample (= 10 mm)

[0369] Table 10 shows the results. The values shown in the table are the average values of the values measured 3 times using each control sample and test sample.

[0370] Table 10

[0371] (mass%)

[0372]

[0373] (2-2) Measurement of hardness

[0374] The aqueous solutions of the control samples and test samples (1) to (6) shown in Table 9 were poured into a stainless steel container having a cylindrical shape (inner diameter: 40 mm, height: 15 mm), and cooled in an 8°C water tank for 2 hours to solidify the solution. The container was then left to stand at 5°C for 15 hours to obtain a gel composition for intraoral use or oral ingestion contained in a container with a diameter of 40 mm and a height of 15 mm (control samples 6-1 to 6-5 and test samples 6-1 to 6-5).

[0375] The hardness (N / m 2 ) of the gel composition for intraoral use or oral ingestion having a cylindrical shape (inner diameter: 40 mm, height: 15 mm) was measured using a texture analyzer (TA-XT-2i (manufactured by Stable Micro Systems) texture analyzer, probe: P / 20 (φ 20 mm)). Specifically, compression measurement was performed twice using a resin plunger with a diameter of 20 mm and a height of 8 mm at a compression rate of 10 mm / s and a gap of 5 mm. The maximum stress at the first compression was defined as the "hardness" (N / m 2). For the measurement, the control sample and the test sample were adjusted to a product temperature of 20°C.

[0376] Table 11 shows the results.

[0377] Table 11

[0378] (mass %)

[0379]

[0380] (3) Evaluation of saliva secretion promoting effect of control sample and test sample (composition for use in the oral cavity or for oral ingestion)

[0381] Using 3 healthy subjects (subjects A to C; average age: 31.3 years old) who had no abnormality in saliva secretion as panelists, the saliva secretion promoting effect of the composition for use in the oral cavity or for oral ingestion (control samples 6-1 to 6-5, test samples 6-1 to 6-5, product temperature: 20°C) and water at 20°C (blank) was evaluated by the following method.

[0382] (a) 10 g of each sample (control samples 6-1 to 6-5, test samples 6-1 to 6-5) was put into the mouth and freely chewed for 20 seconds, and then swallowed at once. 10 g of water was put into the mouth and kept in the mouth for 20 seconds, and then swallowed at once.

[0383] (b) After the swallowing and after 5 seconds, a size of 3.75 cm x 3.75 cm x 4 mm of absorbent cotton was placed under the tongue, and kept for 2 minutes. The weight of the absorbent cotton was measured in advance.

[0384] (c) After 2 minutes, the absorbent cotton was recovered, and the weight was measured.

[0385] (d) From the change in the weight of the absorbent cotton before and after being placed under the tongue, the amount of saliva secretion by ingestion of each sample (blank (water), control samples 6-1 to 6-5, test samples 6-1 to 6-5) was calculated.

[0386] Table 12 and Figure 5 The results are shown. Table 12 shows the amount of saliva secretion, and the breaking strain and the hardness. In order to eliminate individual differences in the amount of saliva secretion, Table 12 and Figure 5 The values normalized by setting the average value of the amount of saliva secretion in each subject determined by using water (blank) as 1 (relative value) are shown.

[0387] Table 12

[0388]

[0389] The average value of the saliva secretion amount was set to 1 by taking the saliva secretion amount (average value) of the blank (water) as the relative value.

[0390] As shown in the above table, a significant difference in the saliva secretion amount was observed between the gel compositions for intraoral use or oral ingestion containing the enzyme-modified isoquercitrin (test samples 6-1 to 6-5) and the gel compositions for intraoral use or oral ingestion not containing the enzyme-modified isoquercitrin (control samples 6-1 to 6-5). The results also confirmed that the saliva secretion amount was significantly promoted and increased by chewing in the mouth or swallowing the gel compositions for intraoral use or oral ingestion containing the enzyme-modified isoquercitrin.

[0391] Experimental Example 7: Salivation-promoting effect of a gel composition for intraoral use or oral ingestion (No. 2)

[0392] The additives of the compositions for intraoral use or oral ingestion containing the enzyme-modified isoquercitrin and the thickening polysaccharide in the proportions shown in Table 13 were dissolved in water (20°C) to prepare the gel compositions for intraoral use or oral ingestion. The saliva secretion promoting effect of the gel compositions for intraoral use or oral ingestion was evaluated according to the method disclosed in Experimental Example 6.

[0393] (1) Preparation of control samples and test samples

[0394] The gel compositions for intraoral use or oral ingestion were prepared according to the following procedure.

[0395] 1. Among the components shown in Table 13, the components (1) to (3) powders were mixed.

[0396] 2. The powder mixture was added to ion-exchanged water (5), heated to 90°C, and dissolved for 10 minutes with stirring at 1300 rpm.

[0397] 3. Component (4) was added to the aqueous solution, and if necessary, the weight was corrected with ion-exchanged water (5).

[0398] 4. The aqueous solution of components (1) to (5) prepared above was placed in a resin container (Lamicon cup, produced by Toyo Jar Co., Ltd.) having a multilayer structure containing an oxygen barrier layer, and the container was sealed.

[0399] 5. The solution was sterilized (85°C, 30 minutes).

[0400] 6. The container was cooled to 8°C to gel the solution, thereby producing the gel compositions for intraoral use or oral ingestion.

[0401] 7. The compositions were stored in a 5°C refrigerator.

[0402] The breaking strain of the composition for intraoral use or oral ingestion thus prepared was 0.511 to 0.526, and the hardness was 41,528 to 54,170 N / m 2 .

[0403] Table 13

[0404]

[0405] * Enzyme-modified isoquercitrin preparation: "San No. 1" (containing 10 mass% enzyme-modified isoquercitrin (converted to rutin), and also containing dextrin as another component), produced by San-Ei Gen F.F.I. Inc.

[0406] ** Proportion (mass%) of α-glucosyl isoquercitrin (converted to rutin) in the test sample (100 mass%)

[0407] (2) Evaluation of saliva secretion promoting effect of the test sample (composition for intraoral use or oral ingestion)

[0408] Using 3 healthy subjects (subjects A to C: average age: 31.3 years old) who had no saliva secretion abnormality in the 3rd position as panelists, the saliva secretion promoting effect of the composition for intraoral use or oral ingestion (control sample 7, test samples 7-1 to 7-5, product temperature: 20°C) and water at 20°C (blank) was evaluated by the following method.

[0409] (a) 10 g of each sample (control sample 7 and test samples 7-1 to 7-6) was put into the mouth and freely chewed for 20 seconds, and the sample was swallowed at once. 10 g of water was put into the mouth and kept in the mouth for 20 seconds, and the water was swallowed at once.

[0410] (b) After swallowing and after 5 seconds, absorbent cotton having a size of 3.75 cm x 3.75 cm x 4 mm was placed under the tongue, and kept for 2 minutes. The weight of the absorbent cotton was measured in advance.

[0411] (c) After 2 minutes, the absorbent cotton was recovered, and the weight was measured.

[0412] (d) From the change in the weight of the absorbent cotton before and after being placed under the tongue, the amount of saliva secretion by ingestion of each sample (blank (water), control sample 7, test samples 7-1 to 7-6) was calculated.

[0413] Table 14 and Figure 6 The results are shown. In order to eliminate individual differences in the amount of saliva secretion, Table 14 and Figure 6The values normalized by setting the average value of the saliva secretion amount in each subject determined by using water (blank) as 1 are shown (relative values).

[0414] Table 14

[0415]

[0416] The average value of the saliva secretion amount is a relative value in which the saliva secretion amount (average value) obtained by ingesting a blank (water) is set as 1.

[0417] As shown in Table 14, although the control sample 7 in the form of a gel not containing enzyme-modified isoquercitrin also increased the saliva secretion amount, the combination of enzyme-modified isoquercitrin and a thickening polysaccharide (test samples 7-1 to 7-6) confirmed to increase the saliva secretion amount more significantly than the control sample. The results further confirmed that the effect of increasing the saliva secretion amount depends on the amount (dose dependency) of enzyme-modified isoquercitrin incorporated.

[0418] The above results of Experimental Examples 6 to 7 indicate that the saliva secretion is significantly increased when a saliva stimulating agent containing a thickening polysaccharide in addition to enzyme-modified isoquercitrin is orally ingested and the gel composition for intraoral use or oral ingestion has a breaking strain of 0.3 to 0.8 or / and a hardness of 500 to 500,000 N / m 2 The results further indicate that the additive of the composition for intraoral use or oral ingestion according to the present application is suitable as an additive for preparing a gel composition for intraoral use or oral ingestion having a specific breaking strain or / and hardness as described above.

Claims

1. The use of enzyme-modified isoquercitrin or enzyme-modified isoquercitrin and thickening polysaccharides in the production of salivating agents for use in the human oral cavity or by oral administration to humans. The enzyme-modified isoquercitrin described therein is a composition containing α-glucosyl isoquercitrin at a content equivalent to rutin of 60% by mass or higher, wherein the α-glucosyl isoquercitrin is a mixture of two or more compounds shown in the following formula: , where n represents an integer from 0 to 6.

2. The use according to claim 1, wherein the thickening polysaccharide is selected from at least one of the following: xanthan gum, locust bean gum, guar gum, tara gum, deacetylated gellan gum, natural gellan gum, pectin, alginate, gelatin, agar, psyllium husk gum, and carrageenan gum, and the salivating agent is in the form of a composition for oral use or oral ingestion.

3. The use according to claim 1, wherein the salivating agent is in the form of a composition for intraoral use or oral ingestion.

4. The use according to claim 1, wherein the salivating agent is in the following form: syrup, health drink, liquid, emulsion, oil, spray, gel, paste, tablet, chewable tablet, lozenge, pill, granule, powder, dry syrup, film or rod formulation.

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