JP2002226369A - Glutamine-containing oral composition - Google Patents

Abstract

PROBLEM TO BE SOLVED: To obtain a glutamine-containing oral composition capable of effectively exhibiting various kinds of useful pharmacological functions possessed by the glutamine in the interior of the body. SOLUTION: This oral composition is characterized in that the composition contains 3-27 pts.wt. glutamine, 2-24 pts.wt. oligosaccharide, 5-45 pts.wt. vegetable fiber, optionally 3-90 pts.wt. reducing sugar and preferably xylitol.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

TECHNICAL FIELD The present invention relates to an oral composition containing glutamine. More specifically, the present invention relates to a glutamine-containing oral composition having an improved composition so that pharmacology such as gastrointestinal mucosal protection of glutamine is more effectively exerted. In the present invention, the oral composition includes a food or a medicine for internal use or a quasi-drug.

[0002]

2. Description of the Related Art Glutamine is the only amino acid that is directly taken into intestinal wall cells and becomes energy. Glutamine has traditionally contributed to maintaining normal intestinal structure and function (Baskerville et al., British Jo
urnal of Experimental Pathology, 61, p. 132 (198
0)) and that it can be used as an antidote (US Patent No. 228381)
No. 7), can be used to treat peptic ulcer (US Pat. No. 2,686,693), and has a protective effect on aspirin-induced gastric ulcer (Okabe et al., Digestive Disease, 20,
p.66 (1975)).

[0003] Ingestion of glutamine in an amount larger than that contained in a normal diet causes atrophy of the intestinal mucosa and pancreas, and other catabolic intestine-related diseases (catabolic dysfunction) caused by increased intestinal permeability. ), It has been reported that a host defense function disease and reduced immune function can be recovered or treated (Japanese Patent No. 3068644, Japanese Patent Publication No. 7-94389,
2000-186034).

[0004]

SUMMARY OF THE INVENTION An object of the present invention is to provide a glutamine-containing oral composition prepared so that various useful pharmacological functions of glutamine can be more effectively exerted in the body. Furthermore, the present invention makes it possible to continuously take the glutamine-containing oral composition by making the composition safe and easy to take, thereby improving and maintaining the gastrointestinal mucosal flora, adjusting the intestinal flora, It is an object of the present invention to provide an oral composition that can exhibit various effects such as improvement and maintenance of nutrient absorption from the intestine and maintenance thereof, and enhancement of immunity.

[0005]

Means for Solving the Problems The inventors of the present invention have made intensive studies to solve the above-mentioned problems, and found that patients with refractory opportunistic infection due to deterioration of the body defense function and immune function were treated with glutamine and glutamine. By administering an oral composition containing a specific ratio of oligosaccharides and dietary fiber, immunity can be restored and good therapeutic results can be obtained even for patients in whom administration of antibacterial agents and antibiotics is ineffective. Was found. The effect was significantly superior to the case where glutamine was administered alone or the composition containing oligosaccharide and dietary fiber was administered alone.

[0006] Furthermore, the present inventors have added a sugar alcohol, especially xylitol, to such an oral composition having excellent pharmacological effects, and thereby obtained a unique combination of glutamine, oligosaccharide and dietary fiber. It has been found that the amino acid odor and the aftertaste are significantly improved, and that a safe and easy to take oral composition can be prepared. According to such a glutamine-containing oral composition having excellent texture and palatability, not only pharmaceuticals but also products used continuously (eating and taking), such as foods and quasi-drugs, are marketed. It was confirmed that the composition was useful as an oral composition effective for improving chronic symptoms such as constipation and diarrhea. The present invention has been developed based on such knowledge.

That is, the present invention is an oral composition described in the following (1) to (3): (1) 3 to 27 parts by weight of glutamine, 2 to 24 parts by weight of oligosaccharide and 5 to 45 parts by weight of dietary fiber An oral composition characterized by comprising: (2) An oral composition comprising 3 to 27 parts by weight of glutamine, 2 to 24 parts by weight of oligosaccharide, 5 to 45 parts by weight of dietary fiber, and 3 to 90 parts by weight of reducing sugar. (3) Glutamine 3 to 27 parts by weight, oligosaccharide 2 to 24 parts by weight, dietary fiber 5 to 45 parts by weight, and xylitol 3 to 9
An oral composition comprising 0 parts by weight. (4) The oral composition according to any one of (1) to (3), which comprises any solid form selected from the group consisting of tablets, pills, chewables and sublingual tablets. (5) The oral composition according to any one of (1) to (4), which is used as an MRSA infection inhibitor. (6) Used for prevention or treatment of constipation or diarrhea (1)
The oral composition according to any one of (1) to (4).

[0008]

BEST MODE FOR CARRYING OUT THE INVENTION The oral composition of the present invention contains 3 to 27 parts by weight of glutamine, oligosaccharide and dietary fiber, respectively.
It is characterized in that it is contained in a proportion of 2 to 24 parts by weight and 5 to 45 parts by weight.

The proportion of glutamine in 100 parts by weight of the oral composition is not particularly limited as long as it is in the range of 3 to 27 parts by weight as described above, but is preferably 10 to 26 parts by weight, more preferably 14 to 22 parts by weight. Department.

The oligosaccharide used in the present invention is a saccharide having a degree of polymerization from disaccharide to dozens of saccharides, which is pharmaceutically or food-hygienically acceptable. It does not matter whether it is different or homo and hetero. Specifically, lactosucralose, lactulose, galactooligosaccharide, transfer galactooligosaccharide, soybean oligosaccharide, raffinose, fructooligosaccharide, palatinose oligosaccharide, palatinose oligolutigosaccharide, gentioligosaccharide, xylooligosaccharide, inulooligosaccharide, levanoligosaccharide, mannooligosaccharide, Chitooligosaccharide, beet sugar and the like can be mentioned. Preferably, they are lactose sucralose and lactulose.

[0011] Each of these oligosaccharides may be used alone or in any combination of two or more.

The mixing ratio of the oligosaccharide in 100 parts by weight of the oral composition is not particularly limited as long as it is in the range of 2 to 24 parts by weight as described above, but is preferably 7 to 21 parts by weight, more preferably 10 to 18 parts by weight. Parts by weight.

The dietary fiber used in the present invention refers to an indigestible polysaccharide or lignin which is pharmaceutically or food-hygienically acceptable, and specifically, guar gum, guar gum hydrolyzate, carrageenan, gum arabic, Konjac mannan, locust bean gum, pullulan, curdlan, xanthan gum, gellan gum, native gellan gum, agar, pectin, low molecular weight pectin, laminaran,
Fucoidan, sodium alginate, low molecular weight sodium alginate, hemicellulose, polydextrose,
Insoluble dextrin and sodium carboxymethylcellulose can be mentioned. Preferably, it is guar gum decomposition product, polydextrose, or insoluble dextrin.

Each of these dietary fibers may be used alone or in any combination of two or more.

The proportion of dietary fiber in 100 parts by weight of the oral composition is not particularly limited as long as it is in the range of 5 to 45 parts by weight as described above, but is preferably 16 to 40 parts by weight.
More preferably, it is 22 to 34 parts by weight.

The oral composition of the present invention may further contain a reducing sugar in addition to the above components. As the reducing sugar used in the present invention, any reducing sugar that is pharmaceutically or food-sanitary acceptable can be used, but preferably xylitol, maltitol and sorbitol can be mentioned. More preferably, it is xylitol. Xylitol is also effective against tooth decay.
Each of these reducing sugars may be used alone or in any combination of two or more.

By using such reducing sugars in combination, the composition containing glutamine, oligosaccharide and dietary fiber in proportions of 3 to 27 parts by weight, 2 to 24 parts by weight and 5 to 45 parts by weight, respectively, has a unique property. Ease amino acid odor, gum odor such as guar gum, or bad aftertaste to eliminate taste problems and enhance palatability so that anyone can take it without resistance. Can be made possible. In particular, according to the above xylitol, maltitol or sorbitol, it is possible to correct the above-mentioned composition containing glutamine, oligosaccharides and dietary fiber in a specific ratio to a preferable taste and to give a refreshing feeling, whereby It can be a long-lasting oral composition that does not get tired.

When the oral composition of the present invention contains these reducing sugars, the content of each component in 100 parts by weight of the oral composition is 3 to 27 parts by weight of glutamine,
The ratio of oligosaccharide 2 to 24 parts by weight, dietary fiber 5 to 45 parts by weight, and reducing sugar 3 to 90 parts by weight can be exemplified.
The mixing ratio of the reducing sugar can be appropriately selected and adjusted from the above range according to the type and indication of the reducing sugar to be used, the type of the oral composition, and the like. To 28 parts by weight.

The oral composition of the present invention may contain, in addition to the above-mentioned components, fillers, extenders, binders, excipients, humectants, disintegrants, surfactants which are usually used in the art as other components. And diluents and excipients such as lubricants and sustained-release agents. In addition, dissolution aids depending on the formulation of the formulation,
Buffers, preservatives, solubilizers, isotonic agents, emulsifiers, suspending agents, dispersants, thickeners, gels, hardeners, absorbents, adhesives, elasticizers, plasticizers, adsorbents, Flavors, colorants, flavors,
Antioxidants, preservatives, humectants, light-blocking agents, brighteners, antistatic agents, coating agents and the like can also be used. Specifically, as an excipient, sucrose, calcium carbonate, lactose,
Corn starch, mannitol, D-sorbitol, crystalline cellulose, erythritol, sucrose, etc .; hydroxypropylcellulose (HPC), hydroxypropylmethylcellulose, polyvinylpyrrolidone as a binder;
Methylcellulose, pregelatinized starch, etc .;
Carmellose calcium, croscarmellose sodium, carboxymethylcellulose, low-substituted hydroxypropylcellulose, cross-linked polyvinyl pyrrolidone, etc .; magnesium stearate, calcium stearate, talc, etc. as lubricants; l-menthol, vanillin, lemon Flavors such as oil, cauliflower oil and peppermint oil and aromatic oils can be exemplified.

The oral composition of the present invention may further contain other physiologically active ingredients and pharmacologically active ingredients, if necessary, as long as the effects of the present invention are not impaired.

The oral composition of the present invention can be prepared into various dosage forms that can be administered orally. Specifically, tablets, chewables (chewables), pills, powders, fine granules, granules,
Examples include solid preparations such as capsules and troches; liquid preparations such as aqueous solutions, oily solutions, suspensions, emulsions, syrups and elixirs. Preferred are solid preparations, among which tablets, chewables (chewables),
Pills, troches, sublingual tablets and the like can be preferably exemplified. In the present invention, the oral composition containing a reducing sugar is itself excellent in texture such as taste and smell due to its formulation (formulation composition). It can be prepared and provided as a naked tablet (naked pill) or the like without using it.

Formulation into these dosage forms can be carried out according to the formulation form by a conventional method, and various forms of formulations can be prepared (edited by Yoshinobu Nakai, development and development of pharmaceutical products). Vol. 11, "Unit operation and machine of preparation", Hirokawa Shoten Co., Ltd., issued on November 10, 1999).

The oral composition of the present invention probably has a protective effect of glutamine on the gastrointestinal mucosa, a growth effect of intestinal bacteria by oligosaccharides and dietary fiber, and a regulating effect on the bacterial flora, thereby improving digestion of the gastrointestinal tract and the like. It is considered to have the effect of restoring the reduced function of the organ to a healthy state. As the function of the digestive tract is improved and enhanced, symptoms such as constipation and diarrhea based on such reduced function are improved, and / or the absorption and digestion of glutamine and nutrients from the digestive tract are promoted. It is thought that the healing power and the immune function (living body defense function) that are originally provided can be improved or improved, and various infectious diseases such as MRSA caused by the decrease of the immune function can be prevented or improved.

The dose per administration of the oral composition of the present invention can be appropriately adjusted according to the subject's age, weight, sex, symptoms to be improved and the degree thereof. Glutamine, oligosaccharides and dietary fiber contained in the composition are used in the range according to the usually administered dose.

The dosage of the glutamine, oligosaccharide and dietary fiber to be incorporated per one dosage form of the oral composition of the present invention, and when the oral composition contains a reducing sugar, the dosage of the reducing sugar may be the same as that of the present invention. It is sufficient that the composition exerts a desired effect, for example, when converted to a daily dose, glutamine is 5 to 12 g and oligosaccharide is 3 to 15 g.
g and dietary fiber 5-30 g, and reducing sugar 5-30
It is possible to mix at a ratio of g.

The oral composition of the present invention may be used as needed according to symptoms, or may be administered once or several times a day, for example, before, after or between meals. .

The oral composition of the present invention can be prepared into various foods according to a conventional method, and can be used for special purpose foods (foods for functional health (foods for nutritional function and foods for specified health use), foods for the sick, etc.). Food (individually evaluated food for the sick), health food, etc.).

[0028]

EXAMPLES Hereinafter, the present invention will be described in more detail with reference to examples, but the present invention is not limited to the examples. In addition, unless otherwise noted in the following examples, parts mean parts by weight. Example 1 Tablet Glutamine (L-glutamine: Ajinomoto Co., Inc.) 18 parts Oligosaccharide (lactosucrose) (trade name: Meioligo: Meiji Seika Co., Ltd.) 14 parts Dietary fiber (guar gum decomposition product) (trade name: Sun Fiber R: Taiyo Kagaku Co., Ltd.) 28 parts xylitol (Danisco Co.) 1 part total 100 parts 2 parts 24 parts corn starch 12 parts citric acid perfume 1 part sucrose fatty acid esters.

Example 2 Tablets Glutamine (L-glutamine: Ajinomoto Co., Inc.) 18 parts Oligosaccharide (lactosucrose) (trade name: Meioligo: Meiji Seika Co., Ltd.) 14 parts Dietary fiber (guar gum: Sanseki Chemical Co., Ltd.) ) 28 parts maltitol (manufactured by Nikken Chemicals Co., Ltd.) 1 part total 100 parts 2 parts 24 parts corn starch 12 parts citric acid perfume 1 part sucrose fatty acid esters.

Experimental Example 1 9.76 g of glutamine, oligosaccharide (fructooligosaccharide)
A daily dose of 7.5 g and 15 g of dietary fiber (guar gum) was orally administered to a subject in three divided doses, and the MRS of the composition of the present invention (glutamine + oligosaccharide + dietary fiber) was obtained.
The preventive and curative effects on A infection were examined. (1) Investigation of Transition of MRSA Occurrence Frequency The frequency of occurrence of MRSA in hospitals was compared before and after the start of administration of the composition, and the preventive effect of the composition on MRSA occurrence was evaluated. Specifically, inpatient 497
The above composition was administered to patients to be subjected to MRSA or the like among the names, and the occurrence of in-hospital MRSA before and after administration was investigated over a year. The results are shown in FIG. As can be seen from the results in FIG. 1, the number of MRSA infections has clearly decreased since the start of administration of the above composition, indicating that the composition of the present invention (glutamine + oligosaccharide + dietary fiber) Administration was considered to be an effective method for suppressing the occurrence of in-hospital MRSA infection. (2) Inhibitory effect of MRSA infection (i) Fasting for more than 1 week, severe trauma,
Acute pancreatitis, sepsis, burn (more than 15% of body surface area)
Of the 71 cases, the composition of the present invention was administered to 33 cases (administration group), and the remaining 38 non-administered cases were used as a control group to compare the incidence of MRSA infection. The inhibitory effect on MRSA infection by administration of the substance was examined.
The results are shown in FIG. As can be seen, the incidence of MRSA infection was 6.1% in the administration group and 21.1 in the control group.
%, Which indicates that the composition of the present invention has an effect of suppressing MRSA infection.

(Ii) Immunity enhancing effect The administration group (n = 33) and the control group (n = 38) of the above (2)
, The peripheral blood lymphocyte count (TLC), which is an indicator of immune competence, was measured after the treatment, and 1398 ± 61 in the administration group.
It was significantly higher than 3 / mm ³ and 788 ± 371 / mm ³ of the control group. Also, when diamine oxidase activity (DAO activity) for evaluating the integrity of intestinal mucosal cells was measured,
3.7 ± 1.4 U / L in the administration group and 1.9 ± 1.2 in the control group.
It was significantly higher than U / L.

(Iii) Effect on artificial respiratory management Eight out of 25 patients equipped with an artificial respirator were administered the composition of the present invention (administration group), and the administration of the composition of the present invention suppressed MRSA infection. Efficacy, remaining 18 untreated
The examples were compared with the control group. In the case of artificial respiration, the incidence of infection after administration of the composition of the present invention was 12.5%, which was significantly lower than the incidence of 29.4% in the non-administration group.
The period until respiratory withdrawal was 8.4 ± 5.9 days in the administration group and significantly shorter than 13.8 ± 9.5 days in the non-administration group.

(Iv) Effect on MRSA enteritis 8 cases of MRSA enteritis, 2 cases of intractable mycosis, and 2 cases of pseudoulcerative colitis (all without treatment with antibiotics or antibacterial agents)
When the composition of the present invention was administered to 2 weeks after the administration, 6 of 8 cases (75%) and 2 of 2 cases (1
00%) and 2 out of 2 cases (100%) showed disappearance of MRSA.

From the above results, the composition of the present invention (glutamine + oligosaccharide + dietary fiber) is useful for restoring and improving immunity, and mainly for MRSA against prolonged fasting cases and severely invasive cases. It is useful for prevention and treatment of nosocomial infection.

Experimental Example 2 The preparation prepared in Example 1 (tablet 1 of the present invention) and a tablet prepared similarly using corn starch instead of oligosaccharide, dietary fiber and xylitol of this preparation (comparative tablet 1) Was taken for 10 days each by panelists having constipation symptoms (paneler 1) and diarrhea or diarrhea symptoms (paneler 2) for 1 day, 3 days, and 7 days And on the tenth day,
Paneler 1 counted the number of bowel movements, and paneler 2 counted the number of bowel movements with diarrhea or diarrhea. The intestinal action of the tablet of the present invention was evaluated by comparing it with the state before taking the bowel. Table 1 shows the results for panelists with constipation
Table 2 shows the results for diarrhea or diarrhea-prone panelists. Each numerical value in the table is the average number of times / day for each of the 15 persons.

[0036]

[Table 1]

[0037]

[Table 2]

From these results, it was found that the oral composition of the present invention works effectively for improving constipation and diarrhea.

Experimental Example 3 The tablets prepared in Example 1 (glutamine + oligosaccharide + dietary fiber + xylitol: tablet 1 of the present invention) and the same procedures were carried out using maltitol, sugar or corn starch in place of xylitol in the tablets. The tablets (inventive tablet 2, comparative tablet 1 or control tablet, respectively) prepared in the above were evaluated for texture by 10 panelists. The texture was evaluated on a 5-point scale (5: good, 4: fairly good, 3: normal, 2: somewhat poor, 1: bad) for the refreshing sensation, good meltability in the mouth, and the absence of residuals such as acne. , Comprehensive evaluation. Table 3 shows the results. The values in the table are the average scores of 10 panelists.

[0040]

[Table 3]

From these results, it can be seen that the addition of a reducing sugar such as xylitol or maltitol in addition to glutamine, oligosaccharides and dietary fiber allows the tablet (control tablet) consisting of glutamine, oligosaccharides and dietary fiber to have a unique Egmi Can suppress the expression of, and more exotic than sugar commonly used as a flavoring agent or sweetener,
It can be seen that tablets having significantly better cooling sensation and good melting in the mouth can be prepared overall. Among the reducing sugars, xylitol is particularly excellent in the effect of improving the texture (no stuffiness, refreshing sensation and good dissolution in the mouth) with respect to the oral composition comprising glutamine, oligosaccharides and dietary fiber.

[Brief description of the drawings]

FIG. 1 is a diagram showing the results of examining the frequency of occurrence of MRSA in a hospital over one year before and after the start of administration of a composition of the present invention (glutamine + oligosaccharide + dietary fiber) in Experimental Example 1 (1). is there.

[Fig. 2] In Experimental Example 1 (2) (i), 71
Among the examples, the incidence of MRSA infection between the group to which the composition of the present invention (glutamine + oligosaccharide + dietary fiber) was administered (N = 33) and the remaining non-administration group (control group) (n = 38) was shown. It is a figure showing the result of comparison.

Continued on the front page (51) Int.Cl. ⁷ Identification symbol FI Theme coat II (Reference) A61K 31/715 A61K 31/715 A61P 1/00 A61P 1/00 1/04 1/04 1/18 1/18 31 / 04 31/04 37/00 37/00 39/02 39/02 F term (reference) 4B018 LE01 LE02 MD19 MD31 MD32 MD34 MD37 ME11 4C076 AA36 BB04 CC16 CC31 4C086 AA01 AA02 EA01 EA20 MA35 MA52 NA05 ZA66 ZA68 ZA72 ZB35 ZC37 4C206 AA01 AA02 CA05 FA53 MA03 MA04 MA55 MA72 NA05 ZA66 ZA68 ZA72 ZB35 ZC37

Claims (6)

[Claims] 1. Glutamine 3 to 27 parts by weight, oligosaccharide 2 to 2
An oral composition comprising 24 parts by weight and 5 to 45 parts by weight of dietary fiber. 2. Glutamine 3 to 27 parts by weight, oligosaccharide 2 to 2
24 parts by weight, 5-45 parts by weight of dietary fiber and 3-9 reducing sugars
An oral composition comprising 0 parts by weight. 3. Glutamine 3 to 27 parts by weight, oligosaccharide 2 to 3
An oral composition comprising 24 parts by weight, 5-45 parts by weight of dietary fiber, and 3-90 parts by weight of xylitol. 4. The oral composition according to any one of claims 1 to 3, wherein the composition is in a solid form selected from the group consisting of tablets, pills, chewables, troches and sublingual tablets. . 5. The oral composition according to claim 1, which is used as an agent for suppressing MRSA infection. 6. The oral composition according to claim 1, which is used for preventing or treating constipation or diarrhea.