JP2018100247A - Dextrin formulation - Google Patents

Abstract

PROBLEM TO BE SOLVED: To reduce the strong bitterness peculiar to a crude drug extract, and further to suppress the harsh taste peculiar to a crude drug extract, thereby improving the feeling of taking dextrin. Providing the formulation. SOLUTION: The dextrin preparation contains a dextrin having a molecular weight of 5000 or less and a crude drug extract, and the dextrin having a molecular weight of 5000 or less can suppress the bitterness peculiar to the crude drug extract. Further, by containing crystalline cellulose, it is possible to suppress the peculiar bitterness of the crude drug extract. [Selection diagram] None

Description

  The present invention relates to a dextrin preparation containing a herbal extract. More specifically, the present invention relates to a dextrin preparation with reduced bitterness derived from a herbal extract and excellent in feel.

Traditionally, herbal extracts have been widely used as pharmaceuticals. As such herbal extracts, those obtained by extracting a specific herbal with water or hydrous alcohol, concentrating and sterilizing are used.
And since most of the crude drug extracts are in the form of a paste, from the viewpoint of ease of taking and storage stability, granules and fine granules or sugar-coated tablets together with excipients and fluidizing agents It is used as a tablet for drugs.

As a preparation containing such a crude drug extract, for example, in Patent Document 1, 30 to 70 parts by mass of an extract powder, 2.5 to 10 parts by mass of an inorganic substance, 20 to 67.5 in total of crystalline cellulose and croscarmellose sodium A tablet containing mass parts and having a mass ratio of crystalline cellulose to croscarmellose sodium of 50/100 to 300/100 is disclosed.
Further, in Patent Document 2, a herbal powder or / and herbal medicine comprising herbal powder is mixed with 5 to 100% by weight of light anhydrous silicic acid, and then compression molded and pulverized to obtain a crude drug powder or / And a herbal medicine granulated product comprising herbal powder.
Moreover, in patent document 3, it is a solid formulation containing a crude drug extract or a Chinese medicine extract and an adsorbent, and the adsorbent has a first adsorbent having an adsorbing capacity of 4 to 6 ml / g and an adsorbing capacity of 2 ml. A solid formulation comprising a second adsorbent that is greater than or equal to / g and less than 4 ml / g is disclosed.
Patent Document 4 discloses a Kampo preparation containing a Kampo dry extract and pregelatinized starch.

JP2012-001474 JP2002-097130 JP2013-032346A JP2013-32351A

  The preparations containing herbal extracts in Patent Documents 1 to 4 are preparations that suppress stickiness, granules having a predetermined hardness, those that can effectively suppress caking (solidification) and discoloration, and high hygroscopicity. Although it has been improved so that it can contain a high concentration of Chinese herb extract, the bitterness derived from herbal extracts has not been improved, and there was a problem in the taste when taking a preparation containing herbal extracts.

A preparation containing a crude drug extract has a problem of ingestion due to bitterness and gummy taste, and the improvement of the ingestion has not been sufficiently achieved, and improvement of the ingestion is desired.
This invention is made | formed in view of the said situation, and it is providing the dextrin formulation which can aim at the improvement of a taking feeling by containing the crude drug extract and suppressing the bitter taste derived from the crude drug extract.

In order to achieve the above object, the gist of the invention of the dextrin preparation according to claim 1 is to contain a dextrin having a molecular weight of 5000 or less and a herbal extract.
The gist of the invention described in claim 2 is that the dextrin preparation according to claim 1 further contains crystalline cellulose.
The invention according to claim 3 is the gist of the invention of the dextrin preparation according to claim 1 or claim 2, further comprising a fluidizing agent and an excipient.
Invention of Claim 4 makes it a summary in the invention of the dextrin formulation as described in any one of Claims 1 thru | or 3. It is a fine granule.
Invention of Claim 5 makes it a summary in the invention of the dextrin formulation as described in any one of Claims 1 thru | or 3. It is a granule.

[Action]
The dextrin preparation of the present invention contains dextrin and a herbal extract. As a result of diligent research, the inventors have found that the use of the dextrin having a molecular weight of 5000 or less can reduce the strong bitterness inherent in the herbal extract and has completed the present invention. In the dextrin preparation of the present invention, by using a dextrin having a molecular weight of 5000 or less, strong bitterness can be suppressed by the herbal extract, and the feeling of taking can be improved.
In addition, some of the herbal extracts have a strong bitter taste in addition to a strong bitter taste, such as Onji extract, and such a strong bitter taste also causes a deterioration in taking feeling. When the dextrin preparation of the present invention further contains crystalline cellulose as an excipient, it becomes possible to suppress the strong taste caused by the herbal extract and to further improve the feeling of dosing.
Moreover, the said dextrin formulation can be made into a solid dosage form suitably by containing a fluidizing agent and an excipient | filler further.
Moreover, the said dextrin formulation can raise the freedom degree of a dosage by using it as a fine granule or a granule.

[effect]
According to the present invention, since the strong bitterness peculiar to a crude drug extract can be reduced, it is possible to provide a dextrin preparation excellent in taking feeling.

Hereinafter, an embodiment embodying the dextrin preparation of the present invention will be described.
The dextrin preparation contains a crude drug extract and dextrin.

The herbal extract is a main component of the dextrin preparation of the present invention, and is extracted from a predetermined herbal medicine. The form of the herbal extract is not particularly limited, and any form of liquid, soft extract, and dry extract can be used.
The method for extracting the herbal extract from the herbal medicine is not particularly limited, and any general extraction method can be employed. As a specific example of the extraction method, the extract obtained from the crude drug according to the method of producing Japanese Pharmacopoeia licorice extract is concentrated, ethanol or water-containing ethanol is quantitatively added and stirred, and separated into a precipitate and a supernatant, A method of concentrating the supernatant, a method of extracting from a crude drug with water or water-containing ethanol at a low temperature, a method of extracting by heating in the same manner, or a method of concentrating after dissolving a suitable amount of saccharides such as xylitol in the extract. It is done. In addition, the soft extract obtained by these extraction methods can be mixed with an excipient such as the dextrin and then made into a dry extract by a general means such as spray drying or freeze drying.

  The herbal medicine is not particularly limited, and any of them can be used. For example, Asenyaku, Ireisen, Weikou, Engosaku, Yuki, Ogi (Yellow), Ogon (Yellow), Oubak (Yellow), Ohi (Sakura), Oulen (Yelen), Onji (Distant), gadgets, kasosou (summer hay), citrus (poisonous), cuckoo (knot root), cuckoo, caronin, valerian, licorice (licorice), chamomile, cypress (kikyo), kikuka (chrysanthemum), pheasant (fruit) , Kyonin (Kyojin), Kyo Katsu, Kujin (Bitter), Keigai (Kai), Keihi (Kinshika), Gentian, Kouka (Safflower), Koubushi (Kosuke), Koubay, Kouboku (Kohpaku), Gouo, Goshitsu (cow) Knee), Goshyu (Kurei), Goboushi (Gyudon), Goshi (Gomi), Psycho (Saiko), Saishin (Spicy), Sanshishi (Yamako), Sanche (Yamabuchi), Salamander (Yamabuchi), Hawthorn (Yamazuko), Sandskon (Yamazune), Sansoonin (Shibanjin), Sanyaku (Yamadaku), Sanna (Yamana), Jiao (Guangdong), Zion, Peonies, Musk, Shouma (Satsuma), Shitsuri, Shazenshi, Shazenso, Shajin (Shukusha (contracted sand)), Beast (including Yutan), Shogyo (ginger), Giryu (land dragon), Shinyi (spicy potato), Zikopi (ground bone) Skin, Sicon, Sexan (gypsum), Gypsum (gypsum), Senega, Senkotsu (river bone), Zenko (former hu), Senkyu, Assembly, Sojutsu (蒼朮), Sohakuhi (mulberry skin), Soyo (Suyo) ), Daio, Daiso, Chikujo, Chikuetsujinjin (Takebushi Ginseng), Chimo (My Mother), Clove (Choko), Chorei (Chi), Chinpi (Chen), Nangzhou (Tiannan Star), Pepper (Winter Lion), Toki (Toki), Tonin (Tomojin), Tokon, Tochu, Nantenjitsu, Carrot (Ginseng), Nindu (Winter Winter), Baimo, Bacmondou, Pepper (lightweight), Hange (half) Summer), peony, peony, peony (birch), biwayo (bamboo leaf), betel loin (lion), bukuryo (茯苓), button pi (peony skin), maou (mao), machinin (masojin), mokko (wooden incense) ), Yokuinin, Ryugannik (Ryuganiku), Ryokyo (Ryokan), Ryukotsu (Kiryu), Ryutan (Ryuboku), Rennik (Lotus Meat), Forsythia (Rengyou) and the like. Among these, from the viewpoint that the dextrin preparation is effective in suppressing strong bitterness and the like, those having strong bitterness and the like are preferable. Specific examples of herbal medicines having such a strong bitter taste include Onji, Chimpi, Kagosou, Bowie, Psycho, Chimo, and the like. In particular, Onji has a strong bitter taste and is suitable for Onji extract.

The dextrin is a low molecular weight polysaccharide and is used as an excipient. Further, in the dextrin preparation of the present invention, the strong bitterness of the herbal extract is covered (hereinafter also referred to as “masking”). used.
The dextrin having a molecular weight (weight average molecular weight) of 5000 or less is used to mask the strong bitter taste of the herbal extract. The molecular weight is preferably 900 or more and 5000 or less, more preferably 1500 or more and 3000 or less. When the molecular weight is outside the above range, the effect of masking the strong bitterness cannot be obtained sufficiently.
The dextrin is generally classified according to dextrose equivalent (DE), with 10 or less being “dextrin”, 10 to 20 being “maltodextrin”, and 20 to 40 being “flour candy”. In these dextrin grades, any grade can be used for masking the strong bitter taste of the herbal extract. However, if the DE is excessively low, problems such as white turbidity, precipitation or powdery odor due to aging during refrigeration may occur, in addition to bitterness masking. From such a viewpoint, the grade of the dextrin is preferably DE or higher, more preferably 4 or higher, and further preferably 5 or higher as DE.
The dextrin content in the dextrin preparation is preferably 20 to 300% by mass, more preferably 30 to 200% by mass, and more preferably 50 to 150% by mass with respect to the solid content of the herbal extract. More preferably. When the content of the dextrin is excessively small, the effect of masking the bitter taste cannot be obtained, and when the content is excessively large, the dosage feeling of the dextrin preparation is increased and the feeling of administration is lowered.

The dextrin preparation may further contain crystalline cellulose. The crystalline cellulose is a refined α-cellulose obtained from a fibrous plant, is tasteless, insoluble in water, and chemically inert, so that it can be used in combination with the dextrin. Is preferable. Furthermore, the crystalline cellulose can mask the strong taste of the herbal extract, and both the bitterness and the taste of the herbal extract can be masked together with the dextrin. The dextrin preparation preferably contains the crystalline cellulose.
Grades of the average particle diameter, loss on drying, bulk density, average degree of polymerization and the like of the crystalline cellulose are not particularly limited, and any grades that are used for pharmaceuticals can be used. Among them, the trade name “Compressle M101” manufactured by Fushimi Pharmaceutical Co., Ltd. is preferable.
The content of the crystalline cellulose in the dextrin preparation is preferably 20 to 300% by mass, more preferably 30 to 200% by mass, and more preferably 50 to 150% by mass with respect to the solid content of the herbal extract. More preferably, it is made into%. When the content of the crystalline cellulose is excessively small, the effect of masking the savory taste cannot be obtained. When the content is excessively large, the dose of the dextrin preparation is increased and the feeling of administration is lowered.

The dosage form of the dextrin preparation of the present invention is not particularly limited as long as it is a solid preparation, and any of tablets, powders, fine granules, granules and the like can be used.
In order to produce the solid preparation, in addition to the dextrin and the crystalline cellulose, sugars such as lactose and starches such as corn starch can be used as excipients. In addition to excipients, fluidizing agents for improving granule fluidity and tablet hardness, such as light anhydrous silicic acid, hydrous silicon dioxide, and talc, magnesium stearate, talc, and hydrogenation A lubricant for increasing the fluidity of the powder by weakening the adhesion between the powders such as vegetable oil can be used.
Of the solid preparations, the dextrin preparation of the present invention is preferably a fine granule or a granule from the viewpoint of a high degree of freedom in dosage.
The fine granule preparation can be prepared by a well-known method, for example, a fluidized bed granulation method. Specifically, it can be prepared by using a soft herbal extract as a binder, adding an appropriate amount of dextrin and / or crystalline cellulose to a fluidized bed granulator, spraying and drying.
The granule can be prepared by a well-known method, for example, a dry granulation method. Specifically, it can be prepared by using a dry granulator (roller compactor) after appropriately adding and mixing an appropriate amount of dextrin and / or crystalline cellulose to a powdery crude drug extract dried by a predetermined method. .
The daily intake of the dextrin preparation varies depending on the herbal extract contained, but for example, in the case of an adult extract, in the case of an adult (over 15 years old), the dried product of the extract is 400 mg to 800 mg. Take 3 times orally in the form of oral administration before or between meals.

In addition to the herbal extracts and excipients, the dextrin preparation has a sweetening agent such as sucralose, aspartame, glycine, acesulfame potassium, saccharin, benzoic acid, sodium benzoate, etc. to the extent that these effects are not impaired. Foods such as preservatives such as ethyl paraoxybenzoate, propyl paraoxybenzoate, butyl paraoxybenzoate, ethanol, citric acid, thickeners, emulsifiers, preservatives, food coloring, flavorings and seasonings, enzymes and antioxidants It is also possible to contain additives such as additives and vitamins.
The content of the additive in the dextrin preparation can be selected from any amount as long as it is within the standard range of pharmaceutical products.

Examples of the present invention will be described below, but the present invention is not limited to these examples.
In the following, the product name “Paindex # 1” manufactured by Matsutani Chemical Co., Ltd. is used for dextrin, the product name “Corn Starch IPY” manufactured by Nippon Food Processing Co., Ltd. is used for corn starch, and Fushimi is used for crystalline cellulose. The product name “Compressle M101” manufactured by Pharmaceutical Company was used.

[Manufacture of crude drug extracts]
As a crude drug, 500 g of dried Onji roots cut to about 5 to 10 mm were used. To this, 5000 mL of normal water was added and heated. After boiling, extraction was performed for 30 minutes, followed by solid-liquid separation to obtain an extract. Thereafter, the extract was concentrated under reduced pressure at 60 ° C. or less to obtain 1000 g of a concentrate. The concentrated solution was freeze-dried to obtain 100 g of a dried onji extract as a crude drug extract.

[Sample Preparation (Part 1)]
(Examples 1-5)
Each sample was obtained by mixing 1 part by mass of dextrin having a different molecular weight in each Example (each molecular weight is described in Table 1) with respect to 1 part by mass of Onji dry extract obtained in the production of the above crude drug extract. .

(Comparative Examples 1 and 2)
Comparative Example 1 was mixed with dextrin having a molecular weight of more than 5000 (molecular weight 8500), and Comparative Example 2 was mixed with 1 part by mass of corn starch to obtain 1 part by mass of Onji dry extract obtained by the production of the above crude drug extract. .

[Evaluation Test (Part 1)]
About each sample of Examples 1-5 and Comparative Examples 1 and 2, the measurer actually took each sample and evaluated the taste by a sensory test. The evaluation was made in five levels of bitterness intensity: 1 (none), 2 (weak), 3 (medium), 4 (strong), and 5 (super strong).
In addition, the dose of each sample was set to be equal to the amount of dried onji extract corresponding to one dose of normal onji preparation.
The results are shown in Table 1.

[Sample preparation (part 2)]
(Examples 6 to 10)
Each sample was obtained by mixing dextrin having an average molecular weight of 2300 in parts by mass shown in Table 2 with respect to 1 part by mass of Onji dry extract obtained in the production of the above crude drug extract.

(Comparative Examples 3 and 4)
Corn starch was mixed at 1 part by mass of Onji dry extract obtained in the production of the above crude drug extract, and each sample was obtained.

[Evaluation Test (Part 2)]
For each sample of Examples 6 to 10 and Comparative Examples 3 and 4, taste was evaluated in the same manner as in the evaluation test (No. 1).
The results are shown in Table 2.

[Sample preparation (part 3)]
(Examples 11 to 15)
Examples 1 to 13 are crystalline cellulose and corn starch, and Examples 14 and 15 are only crystalline cellulose based on 1 part by mass of dried onji extract obtained by the production of the herbal extract and 1 part by mass of dextrin having an average molecular weight of 2300. Were mixed in parts by mass shown in Table 3 to obtain samples.

(Comparative Examples 5 and 6)
Corn starch was mixed at 1 part by mass of Onji dry extract obtained in the production of the above crude drug extract at parts by mass shown in Table 3 to obtain samples.

[Evaluation Test (Part 3)]
About each sample of Examples 11-15 and Comparative Examples 5 and 6, taste was evaluated similarly to said evaluation test (the 1). In the evaluation, the gummy taste intensity was classified into 1 (none), 2 (weak), 3 (medium), 4 (strong), and 5 (super strong) in the same manner as the bitterness intensity.
The results are shown in Table 3.

[Discussion (Part 1)]
As a result of Table 1, it was shown that dextrin having a molecular weight of 5000 or less has an effect of masking the bitter taste of Onji. Moreover, since the bitterness intensity | strength is increasing in Example 5 compared with Examples 1-4, the one where the molecular weight of dextrin is small is considered that the masking effect is large.
As a result of Table 2, it was shown that dextrin has a higher masking effect as its content increases. The effective amount of dextrin was 0.5 parts by mass or more per 1 part by mass of Onji dry extract.
In addition, the minimum of the effective amount of dextrin is 0.5 mass part with respect to 1 mass part of Onji dry extract as mentioned above. Regarding the upper limit of the effective amount, as the amount of dextrin increases, the bitter taste is diluted in the whole preparation, and in that case, even if the excipient has no masking effect other than dextrin, the bitter taste can be alleviated. Conceivable. Therefore, the upper limit of the effective amount is considered to be reasonable within a common sense range for formulation.
As a result of Table 3, it was shown that crystalline cellulose has an effect of masking the taste of Onji. Further, it was shown that the masking effect of crystalline cellulose increases as the content increases. Furthermore, it was shown that the effective amount of crystalline cellulose is 0.2 parts by mass or more with respect to 1 part by mass of Onji dry extract.
The lower limit of the effective amount of crystalline cellulose is 0.2 parts by mass with respect to 1 part by mass of Onji dry extract as described above, and the upper limit is the same as the upper limit of the effective amount of dextrin. It is considered as a general range.

[Sample Preparation and Evaluation Test (Part 4)]
(Examples 21 to 27 and Comparative Examples 21 and 22)
Table 1 shows dextrin, corn starch, binder (hypromellose), fluidizing agent (light anhydrous silicic acid), lactose hydrate, and corn starch with respect to 1 part by mass of the dried onji extract obtained in the production of the above crude drug extract. Each sample was prepared as a fine granule using a fluid granulator using a part of corn starch as a binder.
For each sample, the taste was evaluated in the same manner as in the evaluation test (No. 1). The results are shown in Table 4.

[Discussion (Part 2)]
As a result of Table 4, it was shown that dextrin having a molecular weight of 5000 or less also has an effect of masking the bitter taste of Onji even when the fine granule is used.
When Examples 24-26 are compared, the bitterness is increased in Example 25 where the content of dextrin is low, and therefore, it is shown that the masking effect increases as the content of dextrin increases even in the case of a fine granule. It was.
When Examples 21 to 24 and Example 27 are compared, the bitterness intensity is increased in Example 27. Therefore, even when a fine granule is used, the smaller the dextrin molecular weight, the greater the masking effect.

[Sample preparation and evaluation test (5)]
(Examples 31 to 40 and Comparative Examples 31 and 32)
Dextrin, corn starch, crystalline cellulose, fluidizing agent (light anhydrous silicic acid), lubricant (magnesium stearate), and lactose hydrate are shown for 1 part by weight of the dried onji extract obtained in the production of the above crude drug extract. Each sample was prepared as a granule using a continuous dry granulator using a continuous dry granulator.
For each sample, the taste was evaluated in the same manner as in the above evaluation test (No. 3). The results are shown in Table 5.

[Discussion (Part 3)]
As a result of Table 5, it was shown that, even in the case of a granule, dextrin having a molecular weight of 5000 or less has an effect of masking the bitter taste of Onji, and crystalline cellulose has an effect of masking the taste of Onji.
When Examples 31 to 34 and Example 40 are compared, the bitterness intensity is low in Examples 33 and 34. Therefore, when dextrin and crystalline cellulose are used in combination to form granules, the molecular weight of dextrin is 2000 to 2300. However, the masking effect is considered to be large.
When Examples 34 to 37 were compared, the taste strength increased in Examples 35 and 36, and thus, it was shown that the masking effect was increased as the content of crystalline cellulose was increased even in the case of a fine granule. .

[Sample Preparation and Evaluation Test (Part 6)]
(Examples 41 to 43 and Comparative Examples 41 and 42)
Using 1000 g of finely chopped chimpi, kagosou and bowie as herbal medicines, 10 L of normal water was added to each, heated, extracted for 30 minutes after boiling, and solid-liquid separated to obtain an extract. Thereafter, the extract was concentrated under reduced pressure at 60 ° C. or lower to obtain 2000 g of concentrated solution, respectively. The concentrated solution was freeze-dried to obtain 70 g of chimpi, 100 g of Kagosou, and 130 g of bowie as dry crude extracts.
Next, dextrin and corn starch were weighed out in parts by mass shown in Table 6 and mixed with each 1 part by mass of dried extracts of chimpi, kagosou and bowie, and each sample was prepared.
For each sample, the taste was evaluated in the same manner as in the evaluation test (No. 1). The results are shown in Table 6.

[Discussion (Part 4)]
As a result of Table 6, the effect of masking the bitter taste by dextrin having a molecular weight of 5000 or less was also shown for chimpi, kagosou, and bowie, similar to Onji.

According to the present invention, by using a dextrin having a molecular weight of 5000 or less, it is possible to provide a dextrin preparation that can suppress bitterness peculiar to a herbal extract and can improve the feeling of taking. Have.

Claims (5)

  A dextrin preparation comprising a dextrin having a molecular weight of 5000 or less and a herbal extract.   Furthermore, the dextrin formulation of Claim 1 containing a crystalline cellulose.   The dextrin preparation according to claim 1 or 2, further comprising a fluidizing agent and an excipient.   The dextrin preparation according to any one of claims 1 to 3, which is a fine granule. The dextrin preparation according to any one of claims 1 to 3, which is a granule.