JP2002029978A - Urease inhibitor - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide an urease inhibitor as a naturally occurring matter, high in safety and having high antieruptive function when used in especially paper diapers, wet tissues or the like. SOLUTION: This urease inhibitor comprises, as the active ingredient, an extract derived from at least one kind of plant selected from those belonging to the genus Robinia pseudoacacia, the genus Eucalyptus and the genus Morus alba, Salix Gilgiana Seemen and Magnolia kobus DC. var. borealis Sarg.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

[0001] The present invention relates to a urease inhibitor having an effect of suppressing the activity of urease.
Urease is an enzyme that acts when ammonia is generated from urea.

[0002]

2. Description of the Related Art Urease is an enzyme that catalyzes the hydrolysis of urea to generate ammonia. For example, urease (produced by microorganisms) contained in feces reacts with urea contained in urine excreted out of a living body to generate ammonia. It is thought that when feces and urine are mixed in a diaper, ammonia is generated by the action of urease, and a rise in pH activates proteases and lipases in the feces to induce diaper rash (Pedi
atric Dermatology 3, 2, 102, 1986). It is also known that in the stomach, ammonia is generated by the action of urease produced by bacteria (Helicobacter pylori) present in the stomach, and gastric ulcer is induced. It is considered that if an urease inhibitor acts to suppress the generation of ammonia, diaper rash and gastric ulcer can be suppressed. To date, hydroxamic acids (JP-A-57-104276), hydroxymic acids (JP-A-57-119997) and carbostil derivatives (JP-A-7-101) have been known as urease inhibitors.
No. 862), plant extracts such as Ruscus (JP-A-8-19595)
Have been reported as urease inhibitors.

[0003]

However, among the above-mentioned compounds, synthetic compounds have a problem in terms of safety, and there are few natural products having sufficiently high effects. An object of the present invention is to provide a urease inhibitor which is highly safe and highly effective.

[0004]

Means for Solving the Problems The present inventors have found that extracts of Acacia genus, Eucalyptus genus, Mulberry genus, Nagayanagi and Kitakobushi have urease inhibitory activity. The urease inhibitor obtained in the present invention is derived from natural products and has high safety.

[0005]

BEST MODE FOR CARRYING OUT THE INVENTION Hereinafter, the present invention will be described in detail.

[0006] The extract used in the present invention refers to an extract of one or more plants selected from the group consisting of Acacia plants, Eucalyptus plants, Mulberry plants, Nagayanagi and Kitakobushi.
An organic solvent or water commonly used from leaves, bark or xylem, or an extract extracted with any mixed solvent thereof. To obtain an extract with strong urease inhibitory activity,
It is preferable to use leaves for Acacia plants, Eucalyptus plants, Nagayanagi and Kitakobushi. It is preferable to use bark for mulberry plants. As the organic solvent, for example, ethanol, methanol, lower alcohols such as propanol, propylene glycol, glycols such as butylene glycol, chloroform, dichloromethane, halogenated hydrocarbons such as dichloroethane,
Examples thereof include ethers such as methyl ether, ethyl ether and dioxane; lower fatty acid esters such as methyl acetate, ethyl acetate and butyl acetate; and ketones such as acetone and methyl ethyl ketone. These solvents may be used alone, or may be used as a mixture of two or more arbitrary solvents.

The genus Acacia, Eucalyptus and Mulberry can be used as long as they are plant species belonging to the same genus. They can be used alone or in combination of two or more. For example, Acacia ten
Eucalyptus globulus , E. nitens , and E. ex include eucalyptus such as uimervis , A. parvipinnula , and A. clunies.
serta etc., as the mulberry genus, Morus bombycis Koidz (Yamaguwa), can be used Morus Albal (Morus alba) or the like.

[0008] The extraction method may be a commonly used method, for example, a method in which the raw material is immersed in a solvent for a long time,
There is a method in which extraction is performed while heating and stirring at a temperature lower than the boiling point of the organic solvent, followed by filtration to obtain an extract liquid. Further, as a pre-step of extraction, the raw material may be degreased with a non-polar solvent and the essential oil may be removed before extraction with a solvent, or the essential oil may be extracted with a solvent after removing the essential oil by steam distillation. The obtained extract liquid can be used as it is,
It can also be concentrated and used as an extract (pure component) under reduced pressure. Also, for example, activated carbon, celite,
The color and odor may be removed by treating with an adsorbent such as silica gel before use.

When the extract obtained from the plant is used as a urease inhibitor, the dosage form is not particularly limited, and the extract can be used in the form of liquid, gel, powder, and the like.
Further, the extract can be blended in lotions, sprays, mousses and the like. When a liquid or gel product is used, the extract is preferably contained at 0.00001 to 10% by weight, more preferably 0.001 to 1% by weight. Hereinafter, when indicating the blending amount of the extract, etc., it is indicated as the weight% of the extract pure component.

The urease inhibitor can be used without particular limitation as long as ammonia is generated from urea by the action of urease. For example, it can be used in places such as a barn, an animal breeding room, a toilet, and the like, or can be used on human or animal skin.

The urease inhibitor of the present invention can be contained in diapers, tissues, wipes, sanitary sheets and the like, and can also be used as a wet tissue agent, detergent and the like. When including in diapers, for example,
Applying a liquid composition to a diaper (cloth, paper, nonwoven fabric, etc.) or impregnating and drying; mixing a powdery composition into a diaper; blending the composition into a lotion and applying the lotion to the diaper; And the like.

When used in a disposable disposable diaper having the constitution of top sheet / liquid absorbing layer / back sheet, it is preferable that the top sheet contains an urease inhibitor, and the extract contains 0.001% by weight of the top sheet. ~
A range of 1% by weight is preferred. The most preferred range is 0.
002 to 0.2% by weight.

[0013] When used in wet tissues, the extract may comprise from 0.001 to 1 based on the dry weight of the tissue substrate.
A range of weight% is preferred. The most preferred range is 0.0
02 to 0.2% by weight.

It can also be added to beverages, foods, tablets, capsules, etc., and used as health foods and pharmaceutical raw materials.

When the above extract is used as a urease inhibitor, various components, humectants and acidity regulators generally used in foods, pharmaceuticals, quasi-drugs, cosmetics, etc., as long as the effects of the present invention are not impaired. Components used for stabilizers, surfactants, antioxidants, deodorants, antibacterial agents, and the like can be blended, and two or more components may be blended. It can also be used in combination with other urease inhibitors, protease inhibitors, lipase inhibitors and the like.

Various components generally used in foods, pharmaceuticals, quasi-drugs, cosmetics, etc. include allergy inhibitors, atopic dermatitis inhibitors, itching inhibitors, rough skin inhibitors, lower alcohols, polyhydric alcohols , Flavoring agents, fresheners, animal and plant polysaccharides and their degradation products, animal and plant glycoproteins and their degradation products, microbial culture metabolic components, amino acids and their salts, deodorants, emulsifiers, etc., and can be used in combination. .

Examples of the humectant include aloe extract, life-prolonging grass extract, hypericum extract, barley extract, orange extract, seaweed extract, chamomile extract, cucumber extract, comfrey extract, burdock extract, shiitake extract, jiou extract, perilla extract, sage extract, Duke extract, Cordyceps sinensis extract, Dokudami extract, Hatake shimeji extract, Loquat extract, Grape leaf extract, Fujudaiju extract, Prune extract, Loofah extract, Lobster extract, Maikai extract, Momonoha extract, Lily extract, Apple extract, Almond oil, Olive oil, Sesame oil, Saflower Oil, dimethyl silicone, silicone oil, modified silicone, soybean oil, camellia oil, castor oil, jojoba oil, mink oil, coconut oil, arabinose, galactose,
Xylose, glucose, sucrose, sorbitol, fructose, maltose, maltitol, mannose, beeswax, hyaluronic acid, placenta extract, rhamnose, xylobiose, xylo-oligosaccharide, tuberose polysaccharide, trisaccharide, trehalose, ethylene glycol, soluble collagen, glycerin Glycyrrhizin, chondroitin sulfate, diglycerin, squalane, ceramide-like compound, triglycerin, urea, vitamin C phosphate calcium salt, vitamin E, sodium pyrrolidonecarboxylate, hinokitiol, 1,3-butylene glycol, propylene glycol, liquid paraffin And petrolatum, among which aloe extract, life-extinguisher extract, hypericum extract, and conf Ekisu, perilla extract, sage extract, ceramide-like compound, Houttuynia cordata extract, Hatakeshimeji extract, Biwaekisu, Tilia cordata extract,
Button pear extract, castor oil, jojoba oil, hyaluronic acid,
Placenta extract, rhamnose, xylo-oligosaccharide, trehalose, soluble collagen, glycerin, chondroitin sulfate, squalane, urea, 1,3-butylene glycol and propylene glycol are more preferred, aloe extract, xylo-oligosaccharide, ceramide-like compound, hatakeshimeji extract, urea , 1,3-butylene glycol and propylene glycol are particularly preferred.

Examples of the acidity regulator and the function stabilizer include:
For example, adipic acid, citric acid, trisodium citrate, glycine, glycerin fatty acid ester, gluconodelta lactone, gluconic acid, succinic acid, monosodium succinate, disodium succinate, acetic acid, sodium acetate, DL-tartaric acid, L -Tartaric acid, DL-sodium tartrate, L-sodium tartrate, carbonates, carbon dioxide, lactic acid, sodium lactate, fumaric acid, monosodium fumarate, lysozyme, DL-malic acid, DL-sodium malate, phosphoric acid, phosphoric acid Salts, polymeric phosphates, itaconic acid, phytic acid and the like.

Examples of the surfactant include glycerol fatty acid esters such as glycerol monostearate and polyglycerol trioleate; organic acid monoglycerides;
Propylene glycol fatty acid ester, sorbitan fatty acid ester, sucrose fatty acid ester, lecithin, lysolecithin, polyethylene glycol, polyoxyalkyl ether, polyoxyethylene polyamine, alkylpolyoxyethylene sulfate, alkyl sulfate, acylmethyltaurine, N -Acylglutamic acid salts, alkylamidobetaines and the like.

Examples of the antioxidant include catechin, tocopherol, propolis, ellagic acid, and animal and plant extracts (sage, seri, rosemary, etc.).

The deodorant is not particularly limited as long as it is a substance or an extract having deodorant activity, and examples thereof include extracts of plants and mushrooms, and essential oils.

The antibacterial agent is not particularly limited as long as it is a substance or extract having an antibacterial activity. For example, hinokitiol, triclosan, cetylpyridinium chloride, chlorhexidine gluconate, potassium sorbate, sodium benzoate, animal and plant extracts Products, essential oils and the like.

Hereinafter, the present invention will be described specifically with reference to examples. However, these examples are illustrative, and the scope of the present invention is defined by the claims.

<Production Example 1> Acacia tenuine
rvis , A. parvipinnula , A. clunies ) leaves 50 g in 95% ethanol (1 L), 50% ethanol (1
L), 25% ethanol (1 L) and water (1 L) each for 3 days at room temperature to obtain an extract. This extract was concentrated under reduced pressure to obtain an extract.

<Production Example 2> Eucalyptus glo
bulus , E. nitens , E. exserta ) leaves 50% 95%
Ethanol (1 L), 50% ethanol (1 L),
Extraction was performed with 25% ethanol (1 L) and water (1 L) for 3 days at room temperature to obtain an extract. This extract was concentrated under reduced pressure to obtain an extract.

<Production Example 3> 50 g of leaves of Nagabayana willow were mixed with 95% ethanol (1 L) and 50% ethanol (1 L).
L), 25% ethanol (1 L) and water (1 L) each for 3 days at room temperature to obtain an extract. This extract was concentrated under reduced pressure to obtain an extract.

<Production Example 4> 50 g of leaves of Kitakobushi was added to 9
5% ethanol (1 L), 50% ethanol (1 L)
L), 25% ethanol (1 L) and water (1 L) each for 3 days at room temperature to obtain an extract. This extract was concentrated under reduced pressure to obtain an extract.

<Production Example 5> Mulberry (Yamagwa, Magwa)
50 g of bark of 95% ethanol (1 L), 50%
Ethanol (1 L), 25% ethanol (1 L),
Extraction was performed at room temperature for 3 days with water (1 L) to obtain an extract.
This extract was concentrated under reduced pressure to obtain an extract.

<Example 1> Each of the extracts obtained in Production Examples 1 to 5 was dissolved in the same solvent used for extraction, and the urease inhibitory activity was measured by the following method. Also, as a reagent,
Urea (Wako Pure Chemicals), urease (Wako Pure Chemicals: from beans), phenol (Wako Pure Chemicals), sodium nitroprusside (Wako Pure Chemicals), sodium hypochlorite (Wako Pure Chemicals), sodium hydroxide (Wako Pure Chemicals) ) Was used.

20 μl of 0.1% urea solution, 100 μl of extract sample, urease solution (1.32 U / ml:
200 μl of 0.1 M phosphate buffer (pH 7.0), phenol / nitroprusside sodium solution (phenol 5
g, sodium nitroprusside 25 mg / distilled water 500
1680 μl were mixed and incubated at 37 ° C. for 20 minutes. 2 ml of a mixed solution of sodium hypochlorite and sodium hydroxide (20 ml of 5% sodium hypochlorite, 15 g of sodium hydroxide / 1 L of distilled water) was added, and
After standing for a time, the absorbance at 620 nm was measured. The inhibition rate was determined by the following formula. Inhibition rate (%) = [1
-(S ₁ -S ₀ ) / (C ₁ -C ₀ )], S ₀ : Add extract (add 0.1 M phosphate buffer pH 7.0 instead of enzyme), S ₁ : Add extract (enzyme Addition), C ₁ : Add solvent instead of extract (add 0.1 M phosphate buffer pH 7.0 instead of enzyme), C ₁ : Add solvent instead of extract (add enzyme). The concentration at which the inhibition rate was 50% was defined as IC ₅₀ . Table 1 shows the results.

[0031]

[Table 1]

Examples 2 to 4: Eucalyptus ( E.g.
lobulus ), a topsheet containing the extract at the following content and a baby diaper for infants were prepared at the following contents (Examples 2 to 4,
Comparative example 1).

<Example 2> A basis weight of continuous filaments having a fiber diameter of 1.8 dtex and made of polypropylene was 25
g / m ² of a spunbonded nonwoven fabric, and subjected to hydrophilization treatment with a surfactant, after adding a eucalyptus extract to the surfactant diluent so as to contain 0.002% by weight based on the nonwoven fabric. After preparing the prepared top sheet, peel off the top sheet of a commercially available baby disposable diaper (trade name: Doremi Fine, manufactured by Oji Paper Co., Ltd., L size) and replace it with the top sheet prepared as described above. The obtained disposable diaper was designated as Example 2.

Example 3 Using the spunbond nonwoven fabric used in Example 2, the eucalyptus extract was added to the nonwoven fabric in an amount of 0.1%.
Using a top sheet prepared by adhering so as to contain 02% by weight, a baby disposable diaper L size was prepared in the same manner as in Example 2 to obtain Example 3.

Example 4 Using the spunbonded nonwoven fabric used in Example 2, the eucalyptus extract was added to the nonwoven fabric in an amount of 0.1%.
Using a topsheet prepared by adhering so as to contain 2% by weight, a disposable diaper L for babies and infants as in Example 2
A size was prepared, and this was designated as Example 4.

<Comparative Example 1> Using the spunbonded nonwoven fabric used in Example 2 and using a top sheet prepared without the eucalyptus extract, a baby diaper L size for infants was prepared in the same manner as in Example 2. Then, Comparative Example 1 was obtained. Regarding the disposable diapers prepared in Examples 2 to 4 and Comparative Example 1,
A user test was performed as follows.

Grouping of users: 350 babies (average age 18 months) using L-size baby diapers were randomly divided into 7 groups of 50 each.

Diapers used for each group: Two types of diapers (A, B) were distributed to each group. Group 1 Diaper A: Example 2, Diaper B: Comparative Example 1 Group 2 Diaper A: Example 3, Diaper B: Comparative Example 1 Group 3 Diaper A: Example 4, Diaper B: Comparative Example 1 Group 4 Diaper A: Comparative Example 1, Diaper B: Example 2 Group 5 Diaper A: Comparative Example 1, Diaper B: Example 3 Group 6 Diaper A: Comparative Example 1, Diaper B: Example 4 Group 7 Diaper A: Comparative Example 1, Diaper B: Comparative Example 1

Comparative test method: Diapers A and B were used in the order of diapers A and B for 10 days, respectively, and the mothers received comparative answers on the likelihood of diaper rash. Table 2 shows the results.

[0040]

[Table 2]

As a result of the comparison test, when the ratio of the number of people who determined that the diaper A and the diaper B were less likely to be rash was more than doubled, it was judged that there was a difference in the feeling of use. Also,
If the number of people who judged that it was difficult to get rash exceeded the number of people who thought that both did not change, it was judged that the effect on rash was sufficiently exhibited. In Group 7, no clear difference in rash resistance was observed between Diaper A and Diaper B. Although there are some differences between groups in groups 1 to 6, Examples 2 to 6
The evaluation that the diaper of No. 4 was less likely to be rash was obtained. From the above results, the eucalyptus extract was added to the nonwoven fabric at 0.0
In the diaper using the top sheet containing 02 to 0.2% by weight, the effect of suppressing the occurrence of diaper rash was confirmed.

Examples 5 to 8: Using the 25% ethanol extract obtained from Acacia ( A. tenuinervis ), Nagayanagi, Kitakobushi and Yamaguwa in Production Examples 1 and 3 to 5, at the following contents: A topsheet containing the extract and a baby diaper for infants were prepared (Examples 5 to 8,
Comparative example 1).

Example 5 A topsheet prepared by using the spunbond nonwoven fabric used in Example 2 and adhering so that the Acacia ( A. tenuinervis ) extract contained 0.02% by weight of the nonwoven fabric was used. In the same manner as in Example 2, a baby disposable diaper L size was prepared in the same manner as in Example 2.

Example 6 Using the spunbonded nonwoven fabric used in Example 2 and using a topsheet prepared by adhering a Nagayanagi extract to the nonwoven fabric such that the extract contained 0.02% by weight of the nonwoven fabric. A baby diaper L size was prepared in the same manner as described above.

Example 7 Using the spunbonded nonwoven fabric used in Example 2 and using a topsheet prepared by adhering so that the extract of B. nigra is contained at 0.02% by weight with respect to the nonwoven fabric. In the same manner as in Example 1, a baby diaper L size was prepared.

Example 8 The spunbond nonwoven fabric used in Example 2 was used, and the extract of Yamaguchi was added to the nonwoven fabric in an amount of 0.1%.
Using the top sheet produced by attaching it so as to contain 02% by weight, a baby disposable diaper L size was produced in the same manner as in Example 2 to obtain Example 8.

The user diapers prepared in Examples 5 to 8 and Comparative Example 1 were subjected to a user test in the following manner.

User grouping: 450 babies (average age 18 months) using L-size baby diapers were randomly divided into nine groups of 50 each.

Use diapers for each group: Two types of use diapers (A, B) were distributed to each group. Group 1 Diaper A: Example 5, Diaper B: Comparative Example 1 Group 2 Diaper A: Example 6, Diaper B: Comparative Example 1 Group 3 Diaper A: Example 7, Diaper B: Comparative Example 1 Group 4 Diaper A: Example 8, Diaper B: Comparative Example 1 Group 5 Diaper A: Comparative Example 1, Diaper B: Example 5 Group 6 Diaper A: Comparative Example 1, Diaper B: Example 6 Group 7 Diaper A: Comparative Example 1, Diaper B: Example 7 Group 8 Diaper A: Comparative Example 1, Diaper B: Example 8 Group 9 Diaper A: Comparative Example 1, Diaper B: Comparative Example 1

Comparative test method: Diapers A and B were used in the order of diapers A and B, respectively, for 10 days, and the mothers received comparative answers on the likelihood of diaper rash. Table 3 shows the results.

[0051]

[Table 3]

In Group 9, no clear difference in rash resistance was observed between Diaper A and Diaper B.
In the groups 1 to 8, although there were some differences between the groups, the evaluation that the diapers of Examples 5 to 8 were less likely to be rash was obtained in all the groups. From the above results, it was confirmed that the diaper using the top sheet containing the extract obtained from Acacia, Nagayanagi, Kitakobushi, and Yamaguwa at 0.02% by weight based on the nonwoven fabric was effective in suppressing the occurrence of diaper rash. Was.

Example 9 Commercially available wet tissue (weight of wet tissue base material: 40 g / m ² , impregnation amount of impregnating liquid was 250% based on the weight of wet tissue base material, Co., Ltd.)
The content of the eucalyptus extract was 0 per weight of the wet tissue base material for one piece of the napier brand name “Nepia Miffy & Friends Ass Wiping” (wet tissue base material 40 g / m ² , wet tissue impregnation liquid 100 g / m ² ). It was sprayed uniformly with a hand spray so as to have a wet tissue of 0.02% by weight.

<Comparative Example 2> A sample similar to that in Example 9 but containing no eucalyptus extract using wet tissue was used as Comparative Example 2.

A user test was performed on the wet tissues prepared in Example 9 and Comparative Example 2 in the following manner.

User grouping: baby 150
Names (mean age 18 months) were randomly divided into three groups of 50 each.

Samples used for each group: Two types of disposable diapers (A, B) were distributed to each group. Group 1 Sample A: Example 9, Sample B: Comparative Example 2 Group 2 Sample A: Comparative Example 2, Sample B: Example 9 Group 3 Sample A: Comparative Example 2, Sample B: Comparative Example 2

Comparative test method: Each sample was obtained by uniformly wiping the ass with a wet tissue of sample A,
The diapers were used for 0 days, and then switched to Sample B, and the ass was wiped uniformly, and then the diapers were used for 10 days. The hips were wiped with a wet tissue each time the diaper was changed. A comparative answer was given on the likelihood of diaper rash in mothers. Table 4 shows the results.

[0059]

[Table 4]

In Group 3, no clear difference in rash resistance was observed between Sample A and Sample B. In the groups 1 and 2, although there was some difference between the groups, the evaluation that the ninth embodiment was less likely to cause rash was obtained in any of the groups. From the above results, the eucalyptus extract was added to the wet tissue base at 0.02%.
When the buttocks were wiped with a wet tissue containing weight%, the effect of suppressing the occurrence of diaper rash was confirmed.

The eucalyptus ( E. globulu) obtained in Production Example 2
Table 5 shows a formulation example of a cream to which 25% ethanol extract of s ) was added.

[0062]

[Table 5]

[0063]

The extract of the Acacia genus, Eucalyptus genus, Mulberry genus, Nagayanagi and Kitakobushi obtained by the present invention contains an urease inhibitor and is effective in controlling diaper rash and gastric ulcer.

──────────────────────────────────────────────────続 き Continued on the front page (51) Int.Cl. ⁷ Identification symbol FI theme coat ゛ (reference) A61P 17/16 A61P 17/16 43/00 111 43/00 111 F term (reference) 4C083 AA111 AA112 CC24 DD50 EE11 EE50 FF01 4C088 AB12 AB34 AB59 AB65 AC05 AC06 BA08 MA63 ZA68 ZA89 ZC20

Claims (2)

[Claims] 1. A urease inhibitor comprising, as an active ingredient, an extract extracted from one or more plants selected from the group consisting of Acacia plants, Eucalyptus plants, Mulberry plants, Nagayanagi and Kitakobushi. 2. The solvent used for the extraction is one or two selected from the group consisting of lower alcohols, glycols, halogenated hydrocarbons, ethers, lower fatty acid esters, ketones, and water. The urease inhibitor according to claim 1, which is a mixed solvent of the above.