JP5048238B2 - Oral formulation containing dried walnut extract - Google Patents

Description

  The present invention relates to an oral preparation containing dried walnut extract, and more particularly, to an easy-to-use oral preparation masking the bitterness and astringency unique to dry extract of walnut.

  The walnut is a leaf of bearberry (aka: Bearberry) (scientific name: Arctostaphylos uva-ursi (L.) Sprengel), which contains phenolic glycosides such as arbutin, methylarbutin, galloylarbutingalloyglucose, It has pharmacological actions such as bactericidal action, antiviral action, and melanin production inhibitory action.

  As for this walnut, Japanese pharmacopoeia contains rumors and walrus extract, and decoction, soaking agent, and extract are clinically used as urinary tract antiseptic, astringent, diuretic for pyelonephritis, urethritis, cystitis, etc. Yes. However, this walrus extract has long-lasting astringency at the same time as its unique bitterness, so it is a drug with a very bad aftertaste after taking it, and it has a problem of poor ingestibility and storage stability because it is liquid. .

  In addition, dry powder of walnuts is also known as a powdery extract that uses walnuts as a raw material and has good dosage and storage stability, but this is a drug that has a bitter taste and a long-lasting astringency compared to the walnut extract. Met.

  As described above, dry extract of walnut is more preferable as an oral extract from walnut. However, in order to use it as an active ingredient in oral preparations, it is necessary to mask the bitterness and astringency unique to this product. There is. For this purpose, the use of a corrigent is conceived. However, when sugars such as sucrose and sweeteners that have been used in the past are simply blended, the bitterness is sufficient even if the blending amount is very large. In addition to not being able to mask, it was not possible to eliminate persistent strong astringency in the oral cavity.

In addition, as a preparation using a conventional dry dried walnut extract, a combination of nitrofurantoin and freeze-dried extract of walnut is known (Patent Document 1). It wasn't.
Special table 2004-534792

  Accordingly, an object of the present invention is to provide an oral preparation containing walnuts that is easy to take and has reduced the specific bitterness and astringency of the dried extract.

  In view of such a current situation, the present inventors have intensively studied to obtain an oral preparation that can reduce the bitterness and astringency of the dried walnut extract, and as a result, the dried walnut extract and a plurality of types of sugars are blended in the oral preparation simultaneously. By doing so, it was found that the peculiar bitterness and astringency of the dried extract of walnut can be simultaneously reduced, and the present invention was completed.

  That is, the present invention is an oral preparation characterized in that it contains a dried extract of walnut, a monosaccharide, a disaccharide, and a high-intensity sweetener.

  ADVANTAGE OF THE INVENTION According to this invention, the bitterness and astringency of a dry walnut extract are masked, and the formulation containing a dry extract of a walnut extract which can fully draw out the therapeutic effect excellent in a walnut is obtained.

  Accordingly, the above-mentioned oral preparation containing dried walnut extract can be suitably used in clinical practice such as pyelonephritis, urethritis, cystitis as a urinary tract antiseptic, astringent, diuretic.

  The oral preparation of the present invention comprises a dried extract of walnut, a monosaccharide, a disaccharide, and a high-intensity sweetener.

  The dry extract of walrus urushi, which is a medicinal component of the oral preparation of the present invention, is extracted from leaves of bearberry (also known as bearberry) (scientific name: Arctostaphylos uva-ursi (L.) Sprengel) with water or a solvent such as ethanol. And then further concentrated and dried.

  As the dried extract of walnut, a commercially available product sold by Ask Pharmaceutical Co., Ltd. may be used, or the Japanese Pharmacopoeia 14th revised formulation general formula using Japanese pharmacopoeia standard uwa urushi or uwa urushi extract. You may utilize what was prepared according to the description of "(ii) dry extract agent" in "4. extract agent."

  Specifically, as a method for obtaining a dried extract of walnuts from a walnut, firstly, the walnut is roughly cut, and about 2 to 30 times, preferably about 5 to 20 times, purified water is added, and about 60 ° C. or more, preferably Is heated and extracted at about 90 to 100 ° C. for about 15 minutes to 8 hours, preferably about 20 to 120 minutes to obtain a walnut extract. Next, there is a method in which the walnut extract is filtered and then concentrated under reduced pressure, and further subjected to a drying treatment such as spray drying or freeze drying. At this time, if necessary, purified water, ethanol and / or glycerin may be added to the walnut extract concentrated under reduced pressure. Further, before or after the drying treatment, starch, dextrin, cyclodextrin, lactose, sucrose, mannitol, crystalline cellulose, silicic anhydride, or the like may be added as a carrier.

  Moreover, as a method for obtaining a dried walnut extract from a walnut extract, there is a method of subjecting a commercially available walnut extract sold by Nippon Powder Co., Ltd., Koshiro Pharmaceutical Co., Ltd. or the like to a drying treatment such as spray drying or freeze drying. Can be mentioned. In addition, during the drying treatment, a solvent such as purified water and / or ethanol or a carrier such as starch, dextrin, cyclodextrin, lactose, sucrose, mannitol, crystalline cellulose, or silicic acid is added as necessary. Also good.

  The added amount of dried walnut extract in the dry extract containing dried walnut extract of the present invention (hereinafter, simply referred to as “oral preparation of the present invention”) is usually in the range of 5 to 50% by mass with respect to the total mass of the formulation, preferably Is in the range of 10 to 35 mass%, more preferably 15 to 25 mass%.

  On the other hand, monosaccharides used in the oral preparation of the present invention include glucose (glucose (d-glucose)), fructose (fructose, (d-fructose)), d-galactose, l-galactose, dl-galactose, l-arabinose. , D-ribose, d-xylose, l-xylulose, 6-desoxy-d-glucose, l-rhamnose, l-fucose, d-mannose, l-sorbose, d-tagatose, d-mannoheptulose and sedoh 1 type, or 2 or more types selected from the group which consists of putulose is mentioned. Among these, it is particularly preferable to use glucose.

  The addition amount of these monosaccharides in the oral preparation of the present invention is preferably 0.1 to 10 parts by mass, and particularly preferably 1 to 2 parts by mass with respect to 1 part by mass of the dried extract of walnut.

  Examples of the disaccharide used in the oral preparation of the present invention include trehalose, sucrose (lactose), lactose (lactose), maltose (maltose), isomaltose, cellobiose, gentiobis, chitobiose, melibiose, primverose, visiarose, 1 type or 2 or more types chosen from the group which consists of a rutinose, a turanose, laminaribiose, and soforose are mentioned. Of these, trehalose and sucrose are particularly preferred.

  The addition amount of these disaccharides in the oral preparation of the present invention is preferably 0.1 to 10 parts by mass, and particularly preferably 1 to 3 parts by mass with respect to 1 part by mass of the dried extract of walnut.

  Furthermore, examples of the high-intensity sweetener used in the oral preparation of the present invention include one or more selected from aspartame, stevia sweetener, sucralose, acesulfame K, and alitame. Among these, it is particularly preferable to use aspartame.

  In the oral preparation of the present invention, the amount of these high-intensity sweeteners added is preferably 0.001 to 0.1 parts by mass, particularly 0.01 to 1 part by mass of the dry extract of walnut. It is preferable to set it to -0.05 mass part.

  In addition to the above components, other pharmacologically active components may be further blended in the oral preparation of the present invention. Examples of such pharmacologically active ingredients include Inchinkou, Ogon, Ouren, Kisage, Keihi, Sanshi, Giou, Peonies, Shazenshi, Sojutsu, Diou, Takusha, Chorei, Bukuryo, Elderberry, Bowie, Bowkon, Mokutsu, Couchgrass, Cascara Sagrada, Garana, Cinnamon, Juniper, Saijo, Senna, Bioperine Extract, Hydrangea, Parsley, Butch Milk Thistle Extract, Apple, Rosehip, Pepper, Cinnamon, White Willow Bark, Kelp, Horsetail, Herbal medicines and herbs such as parsley, corn silk, bukko and bromelain, vitamins such as vitamin B6 and ascorbic acid, minerals such as potassium and calcium can be mentioned.

  The oral preparation of the present invention should be formulated in accordance with conventional methods by appropriately blending essential ingredients such as dried walnut dry extract, monosaccharides, disaccharides and high-intensity sweeteners, and if necessary, other pharmacologically active substances. Can be prepared.

  Moreover, in formulating, in addition to the above-described components, conventional pharmaceutical additives corresponding to the respective dosage forms can be blended. Examples of such formulation additives include crystalline cellulose, hydroxypropyl cellulose, low-substituted hydroxypropyl cellulose, hydroxypropyl methylcellulose, crystalline cellulose / carmellose sodium, carboxymethylcellulose, povidone, polyvinyl acetal diethylaminoacetate, erythritol, reduced maltose Water candy, calcium carbonate, calcium lactate, carnauba wax, stearic acid, magnesium stearate, talc, sucrose fatty acid ester, titanium oxide, corn starch, partially pregelatinized starch, pullulan, gum arabic, macrogol, polyoxyethylene polyoxypropylene Glycol, calcium silicate, dimethylpolysiloxane, fumaric acid, anhydrous silicic acid, synthetic aluminum silicate It may include sodium lauryl sulfate, and polysorbate 80. These preparation additives are added to the oral preparation of the present invention as an excipient, binder, fluidizer, disintegrant, solubilizer, suspending agent, stabilizer, preservative, coloring agent, sweetener, flavoring agent. It is added for the purpose of agents and flavoring agents.

  The oral formulation of the present invention is a tablet, granule, fine granule, powder, hard capsule, caplet, soft capsule, pill, dry syrup, chewable tablet, troche, effervescent tablet, drop, orally disintegrating tablet or A solid or semi-solid oral preparation such as a syrup is preferable, and a granule or a dry syrup is particularly preferable.

  A preferred embodiment of the oral preparation of the present invention is a dry syrup preparation containing 1 to 2 parts by weight of glucose, 1 to 3 parts by weight of trehalose, and 0.01 to 0.05 parts by weight of aspartame with respect to 1 part by weight of dried walnut extract. Is mentioned.

  The oral preparation of the present invention thus obtained can be used as a urinary disinfectant or diuretic for the treatment and prevention of cystitis, urethritis, pyelonephritis, nephritis and the like. When used for these treatments and preventions, the daily dose for an adult is in the range of 100 to 4000 mg, preferably in the range of 500 to 2000 mg, more preferably in the range of 1000 to 1500 mg as dry dried walnut. . Moreover, when the said dosage is converted into a crude drug substance, it exists in the range of 0.5-40g, Preferably it is the range of 2.5-20g, More preferably, it is the range of 5-15g. The oral preparation of the present invention may be taken before or between meals by dividing the daily dose into 1 to 3 times a day.

  The present invention will be described in more detail with reference to the following examples, but the present invention is not limited to these examples.

Reference example 1
Preparation of dried walnut extract:
100 kg of Japanese Pharmacopeia standard walnuts were used as raw materials, and 12.5 kg of dried walnut extract was prepared in accordance with the description of “(ii) Dry extract” in “14. . In all the following examples, this dried walnut extract was used.

Example 1
Dry syrup:
The following prescription ingredients were mixed for 3 minutes using a stirring granulator, and then pharmacopeic ethanol was added to the mixture and kneaded for 5 minutes. This kneaded product was granulated with an extrusion granulator (diameter: 1.0 mm), dried, adjusted and sieved to obtain 14-42 mesh granules. To 1900 g of this granule, 38 g of light anhydrous silicic acid was added and mixed with a mixer for 5 minutes to obtain a dried syrup containing dry dried syrup of the present invention.

(Prescription)
417 g dry dried extract
980 g of trehalose
40g refined white sugar
Glucose 493g
Aspartame 10g
Low substituted hydroxypropylcellulose 10g
Crystalline cellulose carmellose sodium 10g

Example 2
Dry syrup:
14-42 mesh granules in the same manner as in Example 1 using 658 g dry dried extract, 595 g trehalose, 63 g purified white sugar, 658 g glucose, 7 g aspartame, 16 g low-substituted hydroxypropylcellulose and 16 g crystalline cellulose carmellose sodium Got. To 1900 g of this granule, 37 g of light anhydrous silicic acid was added and mixed for 5 minutes with a mixer to obtain a dry syrup containing dried walnut extract of the present invention.

Example 3
Dry syrup:
14-42 mesh granules in the same manner as in Example 1 using 323 g of dried walnut extract, 937 g of trehalose, 31 g of purified white sugar, 645 g of glucose, 10 g of aspartame, 8 g of low-substituted hydroxypropylcellulose and 8 g of crystalline cellulose / carmellose sodium Got. To 1900 g of this granule, 37 g of light anhydrous silicic acid was added and mixed for 5 minutes with a mixer to obtain a dry syrup containing dried walnut extract of the present invention.

Example 4
Dry syrup:
14-42 mesh granules are obtained in the same manner as in Example 1 using 1559 g of dried walnut extract, 156 g of trehalose, 156 g of glucose, 16 g of aspartame, 38 g of low-substituted hydroxypropylcellulose and 38 g of crystalline cellulose / carmellose sodium. To 1900 g of this granule, 37 g of light anhydrous silicic acid was added and mixed for 5 minutes with a mixer to obtain a dry extract containing walnut dry extract of the present invention as a dry syrup.

Example 5
Dry syrup:
Using 125 g dry dried extract, 1238 g trehalose, 12 g purified sucrose, 750 g glucose, 12.5 g aspartame, 3 g low-substituted hydroxypropylcellulose and 3 g crystalline cellulose carmellose sodium, 14 to 42 mesh in the same manner as in Example 1. A granule was obtained. 37.6 g of light anhydrous silicic acid was added to 1900 g of this granule and mixed with a mixer for 5 minutes to obtain a dry syrup containing a dried walnut extract of the present invention.

Comparative Example 1
Dry syrup:
14-42 mesh granules were obtained in the same manner as in Example 1 using 869 g of dried walnut extract, 1057 g of glucose, 21 g of aspartame, 21 g of low-substituted hydroxypropylcellulose and 21 g of crystalline cellulose / carmellose sodium. 37.5 g of light anhydrous silicic acid was added to 1900 g of this granule and mixed for 5 minutes with a mixer to obtain a dry syrup containing dried walnut extract.

Comparative Example 2
Dry syrup:
14-42 mesh granules were obtained in the same manner as in Example 1 using 557 g of dried extract of walnut, 1336 g of trehalose, 55 g of purified white sugar, 14 g of aspartame, 14 g of low-substituted hydroxypropylcellulose and 14 g of crystalline cellulose / carmellose sodium. . 37.4 g of light anhydrous silicic acid was added to 1900 g of this granule and mixed with a mixer for 5 minutes to obtain a dry syrup preparation containing dried walnut extract.

Comparative Example 3
Dry syrup:
14-42 mesh granules were obtained in the same manner as in Example 1 using 419 g of dried walnut extract, 980 g of trehalose, 40 g of purified white sugar, 493 g of glucose, 10 g of low-substituted hydroxypropylcellulose and 10 g of crystalline cellulose / carmellose sodium. . 37.2 g of light anhydrous silicic acid was added to 1900 g of this granule and mixed for 5 minutes with a mixer to obtain a dry syrup containing dried walnut extract.

Test example 1
A sensory test was conducted on 10 subjects using the dry syrups produced in Examples 1 to 5 and Comparative Examples 1 to 3. In this sensory test, first, each dry syrup was weighed to an equivalent amount of 417 mg of dried walnut extract, and then suspended and dissolved in 100 mL of water. Subsequently, this was included in the mouth for 10 seconds, and bitterness and astringency were evaluated according to the following evaluation criteria. The average evaluation score in this test is shown in Table 1 below. Moreover, what carried out the same sensory test using what suspended and melt | dissolved 417 mg of dried dried walnuts in 100 mL of water was made into the control | contrast.

<Bitter taste evaluation criteria>
(Contents) (Points)
Very strong bitterness: 5 points Somewhat strong bitterness: 4 points Bitterness: 3 points Somewhat bitter: 2 points No bitterness: 1 point

<Convergence evaluation criteria>
(Contents) (Points)
Very strong: 5 points Somewhat strong: 4 points Available: 3 points Weakly present: 2 points None: 1 point

  As a result of the test, it was found that the dry syrup of the present invention was excellent in taking feeling without being bitter and astringent even when it was suspended and dissolved in water. Moreover, the dry syrup of the comparative example which does not contain any of a monosaccharide, a disaccharide, and a high-intensity sweetener did not improve bitterness and astringency at all.

The oral preparation of the present invention can be suitably used for the treatment of pyelonephritis, urethritis, cystitis, etc. as urinary tract antiseptic, astringent, diuretic.
that's all

Claims (3)

  An oral preparation characterized by containing dried walnut extract, glucose, trehalose and aspartame.   The oral dose according to claim 1, wherein 0.1 to 10 parts by weight of glucose, 0.1 to 10 parts by weight of trehalose and 0.001 to 0.1 parts by weight of aspartame are contained per 1 part by weight of dried walnut extract. Formulation.   A tablet, granule, fine granule, powder, hard capsule, caplet, soft capsule, pill, dry syrup, chewable tablet, troche, effervescent tablet, drop, orally disintegrating tablet or syrup The oral preparation according to 1 or 2.