KR19980076998A - Herbal medicine with reduced sedimentation and improved taste - Google Patents

Abstract

The present invention relates to a herbal liquid with reduced precipitation and improved taste. More specifically, the present invention contains 0.1 to 5 w / v% of cyclodextrin liquid and 0.05 to 5 w / v% of poloxamer, thereby suppressing sediment formation over time, thereby improving storage stability, and masking the bitterness and taste unique to herbal medicines. The present invention relates to an herbal medicine that is improved pharmaceutical form by making it less objectionable when taking.

Description

Herbal medicine with reduced sedimentation and improved taste

The present invention relates to a herbal liquid with reduced precipitation and improved taste. More specifically, the present invention contains a cyclodextrin liquid 0.1-5 w / v% and poloxamer 0.05-5 w / v% to suppress the sedimentation formation over time to improve the storage stability, and to improve the bitterness and taste of the unique herbal medicine The present invention relates to a pharmaceutical formulation which is improved in a pharmaceutical form by shielding it so that there is no objection when taken.

In general, the following items must be considered in order to manufacture herbal liquids for commercial use.

(1) Uniformity of the active ingredient content-When the herbal extract is concentrated to an appropriate amount, there may be a part with a high concentration, and precipitation may precipitate during cooling, resulting in a lack of uniformity of the active ingredient. There is.

(2) Precipitation Formation-After preparing a liquid and dispensing in each package for commercial use, the components may react with each other to precipitate precipitates, which not only lowers the value of the commodity but may also contain a main component that exhibits efficacy during precipitation. There is a problem that can not sufficiently exhibit the desired pharmacological effect. Therefore, a precipitation inhibitor should be used to prevent this.

(3) Addition of Preservatives-Herbal liquids are liquids of organic substances, so an appropriate amount of preservatives should be used to prevent contamination by bacteria during the storage period.

(4) Use of copulation agent-Herbal medicine is a hot water extract of herbal medicine. In most cases, it is hard to take because of taste, sourness, sourness and unique peculiar taste of herbal medicine. Therefore, a copper should be used to mask the taste or reduce the specific odor.

As mentioned above, in general, herbal medicines are prepared by adding 10-20 times the amount of water to the herbal medicines, heating them, and extracting them at about 100 ° C. for 2 to 3 hours. In addition, since all the components soluble in water are extracted, there are problems such as the formation of precipitates due to the interaction of these components and the change of temperature and other conditions in storage, and the like. There was a difficulty in developing a good quality product.

Among the problems caused by the formulation of herbal medicines, the most important and difficult problem to solve in order to increase the product value of the herbal medicines and to facilitate taking is the prevention of precipitation formation and the improvement of taste.

Conventionally, suspending agents such as gelatin, casein, carboxymethylcellulose, polyvinylpyrrolidone, and gum arabic were used for the purpose of preventing precipitation in the preparation of herbal liquids. Syrups such as starch syrup, white sugar, glucose, and orange oil, peppermint oil, rose oil, cinnamon oil, lavender oil, menthol, vanilla, ethyl vanilla and the like were used. However, the conventional methods for preventing precipitation and improving taste and specific odor have insufficient effects of preventing precipitation or masking bitter or irritating odor from the herbal medicine itself during the use and storage period of the herbal liquid. Therefore, a method of using various additives has been tried to improve the above-mentioned disadvantages of the herbal liquids, but a method which has not been clearly improved yet has not been developed.

Therefore, the present inventors conducted intensive research to find a component that can improve the disadvantages of the herbal liquids as described above with respect to various additives used in the field of synthetic pharmaceuticals, and in recent years, in the field of synthetic pharmaceuticals, The study was conducted on cyclodextrins and poloxamers, which are known to be safe and safe.

Cyclodextrins, i.e., cyclodextrins α, β or γ or complexes thereof, are known in the field of formulation of synthetic drugs under other names such as Shardinger dextrins, Cycloamyloses and Cyclologans. It has been applied to dissolution aids such as prostaglandins, steroids and barbitals, chemical stabilizers such as aspirin, epinephrine and vitamins, and taste and odor improving agents such as prostaglandins and alkyl parabens. Generally used cyclodextrin solution is a complex of cyclodextrin α, β and γ types, which is produced by the action of cyclodextrin transglycosidase in a medium containing starch, and has an LD ₅₀ value of 10 g when orally administered to rats. It is reported to have a high value of / kg or more, and since only a small amount is absorbed in the gastrointestinal tract, it is a material having safety with little toxicity.

Poloxamer is another name such as Pluronic, Poloxalkol, Monolan and Superonic. It is mainly used for moisturizers, solubilizers and suspending agents in liquid preparations. have. Poloxamer also showed a high LD ₅₀ value of 15 g / kg or more upon oral administration to five animals. intravenous administration is a safe substance upon which the report does not show the symptoms of toxicity as bar higher the value of LD ₅₀ 0.1g / ㎏ and 1.0g / ㎏ respectively.

Through various experiments, the present inventors can add cyclodextrin and poloxamer in specific ratios and add them to herbal liquids to effectively prevent the formation of precipitates that have been a problem in the formulation of herbal liquids, as well as mask unpleasant taste. It was confirmed to complete the present invention.

Accordingly, the present invention relates to a herbal medicine containing cyclodextrin liquid and poloxamer, which effectively prevents precipitation and improves taste.

More specifically, an object of the present invention is to improve the effect of preventing the formation of precipitates by adding a cyclodextrin solution 0.1-5w / v% and poloxamer 0.05-5w / v% and preventing unpleasant writing, steaming and sourness peculiar to herbal medicines. It is to provide a herbal medicine. When cyclodextrin solution or poloxamer is added in an amount of less than 0.1w / v% and 0.05w / w%, respectively, the desired effect is not sufficiently exhibited in the present invention, and cyclodextrin solution is a homologue of cyclic oligosaccharide, If the cyclodextrin liquid exceeds 5w / v% because it is a liquid, it may be a cause of a poorly clogged liquid due to the liquid around the bottle cap during preparation, and crystals may precipitate and become cloudy during cooling. If the poloxamer exceeds 5w / v%, the sulphate slightly bitter taste of the poloxamer itself is violated, which is not preferable because it violates the purpose of the present invention to improve the taste. In particular, it is preferable to contain 1 to 3 w / v% of the cyclodextrin liquid and 0.1 to 1 w / v% of the poloxamer.

According to the present invention, the combination of cyclodextrin and poloxamer in the above ratio provides an advantage that the prevention of precipitation formation and the unpleasant taste masking effect are synergistically excellent compared to the case of using each component alone.

Specific examples of the cyclodextrin liquid used in the present invention may be mentioned Serdedix SL-20 (manufactured by 日本 食品 化工 株式會社), poloxamer is a polyoxyethylene-polyoxypropylene copolymer, a representative example thereof is polox Sammer 188 (trade name: Lutrol F68, BASF) or poloxamer 407 (trade name: Lutrol F127, BASF).

There is no particular limitation in the herbal liquids which can achieve the effects as desired in the present invention by adding cyclodextrin and poloxamer, and may be applied to any herbal liquid prepared by hydrothermal leaching. Specific examples of such herbal preparations may include the prescriptions of the prophylactic agents described in Dong Bobogam, which is the representative herbal medicine of Korea, and other prescription preparations that can be prepared as other prophylactic agents. Representative examples include Hwanggi-tang, vigorous yunjojinjineum, Sangbaekpi-tang, Jaumyangyoungtang, Mundongumja, Cheonhwasan, Okcheonsan, Hwangnyeonjihwangtang, Saengjihwangjain, Ginseng paddoksan, Cheongantang, Cheongsinbotang, Odutang, Goyeontang, Gagambaekhotang, Sagunjatang, Bojungikgitang, Samultang, Dangguibohyeoltang, Guibitang, Sogunjungtang , Gal Geun-tang, Daeseunggi-tang, Jowiseunggi-tang, rhubarb-bujatang, Dashhotang, etc. may be mentioned, but is not particularly limited to these.

The present invention is explained in more detail by the following examples, but the present invention is not limited in any way by these examples.

Example 1

The raw herbal medicines of Hwanggi-tang described in Dongbobogam, raw dried sulfur, Astragalus, Bokryeong, Chunhwa flour, Macmun-dong, Schisandra chinensis and licorice, respectively, were taken in the amounts shown in Table 1, and then placed in an extraction container. After extracting at 100 ° C. for 1 hour and 30 minutes, it was filtered through a 75 μm filter paper, and 60 ml of the extract was put into a preparation tank, followed by D-sorbitol and genebia 50 (50% stevioside + 50% soluble dextrin) in the amounts shown in Table 1. After dissolving by adding cyclodextrin solution, citric acid, poloxamer and sodium benzoate, the solution was sterilized at 95 ° C. for at least 10 minutes, and then, sterilized and purified water was added so that the total amount was 100 ml and filled into a transparent glass bottle.

TABLE 1

Ingredient (g / 100mL) Composition 1 Composition 2 Composition 3 Composition 4 Composition 5 Composition 6 Composition 7 Composition 8 Composition 9 Composition 10 Composition 11 Composition 12 Fresh green 2.5 2.5 2.5 2.5 2.5 2.5 2.5 2.5 2.5 2.5 2.5 2.5 Yellow flag 1.25 1.25 1.25 1.25 1.25 1.25 1.25 1.25 1.25 1.25 1.25 1.25 Ghost 1.25 1.25 1.25 1.25 1.25 1.25 1.25 1.25 1.25 1.25 1.25 1.25 Cloth flower 1.25 1.25 1.25 1.25 1.25 1.25 1.25 1.25 1.25 1.25 1.25 1.25 Mac Moon Dong 1.25 1.25 1.25 1.25 1.25 1.25 1.25 1.25 1.25 1.25 1.25 1.25 Schisandra 0.63 0.63 0.63 0.63 0.63 0.63 0.63 0.63 0.63 0.63 0.63 0.63 Licorice 0.63 0.63 0.63 0.63 0.63 0.63 0.63 0.63 0.63 0.63 0.63 0.63 D-sorbitol 9 9 9 9 9 9 9 9 9 9 9 9 Geneva 50 0.03 0.03 0.03 0.03 0.03 0.03 0.03 0.03 0.03 0.03 0.03 0.03 Citric acid 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 Sodium benzoate 0.06 0.06 0.06 0.06 0.06 0.06 0.06 0.06 0.06 0.06 0.06 0.06 Cyclodextrin - 0.5 One 2 3 4 - - - 2 2 2 Poloxamer - - - - - - 0.25 0.5 One 0.25 0.5 One

Example 2

Liquid prepared after 3 days, 7 days, 14 days, 1 month, 2 months, 4 months and 6 months while preserving the liquid prepared according to the composition shown in Table 1 in Example 1 in a life tester of 40 ℃ The precipitation and taste changes of were tested visually and taste. The measured results are shown in Table 2 below.

TABLE 2

Preservation period Start of test 3 days 7 days 14 days 1 month 2 months 4 months 6 months One Sedimentation - - + ++ +++ +++ +++ +++ flavor Write hard Write hard Write hard Write it down Write hard Write hard Use more and lose Use more and lose 2 Sedimentation - - - - + ++ +++ +++ flavor Write hard Write hard Write hard Write hard Write hard Write hard Write hard Use more and lose 3 Sedimentation - - - - - + ++ +++ flavor Write it down Write it down Write it down Write it down Write it down Write it down Write it down Use more and lose 4 Sedimentation - - - - - - + ++ flavor Hard to wear Hard to wear Hard to wear Hard to wear Hard to wear Hard to wear Hard to wear Written more 5 Sedimentation - - - - - - + + flavor Hard to wear Hard to wear Hard to wear Hard to wear Hard to wear Hard to wear Hard to wear Written more 6 Sedimentation - - - - - - + + flavor Hard to wear Hard to wear Hard to wear Hard to wear Hard to wear Hard to wear Hard to wear Written more 7 Sedimentation - - - - - + ++ ++ flavor Write it down Write it down Write it down Write it down Write it down Write it down Write it down Write it down 8 Sedimentation - - - - - - + ++ flavor Wear it slightly Wear it slightly Wear it slightly Wear it slightly Wear it slightly Wear it slightly Wear it slightly Wear it slightly 9 Sedimentation - - - - - - + + flavor Slightly steamed Slightly steamed Slightly steamed Slightly steamed Slightly steamed Slightly steamed Slightly steamed Slightly steamed 10 Sedimentation - - - - - - - + flavor Write slightly Write slightly Write slightly Write slightly Write slightly Write slightly Write slightly Write slightly 11 Sedimentation - - - - - - - - flavor Taste good Taste good Taste good Taste good Taste good Taste good Taste good Taste good 12 Sedimentation - - - - - - - - flavor Taste good Taste good Taste good Taste good Taste good Taste good Taste good Taste good

In the table,-means no sedimentation, + means that the small amount of sedimentation is observed with the naked eye when observed in detail, ++ means that the sedimentation is easy to identify with the naked eye, , +++ means that a significant amount of precipitation occurs.

As shown in Table 2, the liquid of Composition 1 (the formulation without adding cyclodextrin or poloxamer as the basic prescription of Hwanggi-tang described in the agreement) was precipitated from 2 weeks after storage, and taste and taste increased as time passed. It was more sour and sore. On the other hand, the compositions 4, 5, and 6, in which 2 g, 3 g, or 4 g of the cyclodextrin solution was added to the composition 1, had no precipitation observed at 40 ° C. for 2 months, and the astringency was slightly masked. In addition, in the compositions 1 and 8, in which 0.5 g or 1 g of poloxamer was added to composition 1, no precipitation was observed at 40 ° C. for 2 months, and the taste was almost masked of bitter taste.

However, according to the present invention, in the composition 1, the composition 11 in which 2 g of cyclodextrin solution and 0.5 g of poloxamer were added, and in composition 12 in which 2 g of cyclodextrin solution and 1 g of poloxamer were added together, precipitated even after 6 months at 40 ° C. No formation was observed, and the bitter and bitter taste was almost masked and remained good to take. From these results, it can be seen that the precipitation inhibiting effect and the taste masking effect is excellent when the two components were mixed and added to the Hwanggi-tang than when the cyclodextrin liquid and poloxamer were used alone, respectively.

According to the results of Example 2, below, the herbal liquid preparation according to the present invention was added to various herbal liquid compositions in a ratio of 2 g of cyclodextrin liquid and 0.5 g of poloxamer per 100 ml of liquid solution, thereby suppressing precipitation formation and masking an unpleasant taste. Was prepared.

Example 3

According to the prescription of Hwanggi-tang, which is loaded with Dongbobogam, 250g of raw dried turmeric, 125g of Hwanggi, Bokryeong, Cheonhwa-bun, and Mcmun-dong, 63g each of Schisandra chinensis and licorice are weighed and placed in an extraction container. The mixture was added and extracted at 100 ° C. for 1 hour 30 minutes, and then filtered through a 75 μm filter paper. 6 L of the extract was added to the preparation tank, followed by dissolving by adding 900 g of D-sorbitol, 3 g of Geneva 50, 200 g of cyclodextrin solution, 10 g of citric acid, 50 g of poloxamer and 6 g of sodium benzoate, and sterilizing at 95 ° C. for at least 10 minutes. The stock solution was prepared by fitting the 10L mark and filled into 100 ml clear glass bottles.

Example 4

According to the prescription of the active blood lubricated algae saengmum, weighed 125g each of cheonmundong, mackmundong, schisandra chinensis, fruit fruit, mazain, donkey, simmered sulfur, saengjihwang, chrysanthemum and licorice, and processed according to the same method as in Example 3. To prepare a blood-liquid lubricated algae.

Example 5

According to the recipe of Sangbaekpitang, which is loaded with Dongbobogam, 250g of Donggeunsangbaekpi, Baekboknyeong, Ginseng, Macmundong, brown root, 125g of ginseng and cinnamon, and 63g of licorice were weighed and processed in the same manner as in Example 3 to prepare Sangbaekpitang. It was.

Example 6

According to the prescription of Jaumyang Yeongtang, which was loaded in Dongbobogam, weigh 250g of Angelica ginseng, 188g of ginseng and raw sulfur, respectively, Mcgumdong, Baekjak, Jimo and Hwangbaek, weighing 125g and 63g of licorice, and taking 500 grains of Omija in the same manner as in Example 3. Processing was prepared according to the Jain Yangyangtang.

Example 7

According to the prescription of Mundong-mum, registered in Dongbogam, weigh 250g of Macmun-dong, Schisandra chinensis, Ginseng, Gigolpi, Baekbokryeong and Licorice each, and weigh 100g of ginger and process 100 g of ginger to prepare the Mundong-mum solution. It was.

Example 8

According to the prescription of Tianhua Mountain, which was loaded in Dongbobom, 250g of raw powder, 250g of raw dried sulfur, 250g of brown root, 125g of dried root, 125g of gimmun-dong, 125g of Schisandra chinensis, 63g of licorice and 60g of weighing rice were weighed and processed according to the same method as in Example 3 Was prepared.

Example 9

According to the prescription of Okcheon-san loaded in Dongbobogam, 250g of cheonhwa flour, brown root powder, ganmun-dong, saengjihwang, Schisandra chinensis and licorice were weighed out and processed in the same manner as in Example 3 to prepare Okcheonsan liquid.

Example 10

According to the prescription of Hwangnyeonjihwangtang in Dongbobogam, weigh 125g each of Hwangnyeon, Saengjihwang, Cheonhwabun, Schisandra flour, Schisandra chinensis, Angelica, Ginseng, dried fish, Baekbokyeong, Macmundong and Licorice, and take 67 pages of ginger, 33 dates of jujube and 330 leaves of porridge. It was processed in the same manner as in Example 3 to prepare a Hwangyeonjihwangtang.

Example 11

According to the prescription of Saengjihwang Sounded by Donggibogam, 125g and 63g each of ginseng, raw dried sulfur, riped sulfur, huanggi, astronomical dong, mackmun-dong, crust, Seokgok, Sangbaekpi and Taeksa were weighed and processed according to the same method as in Example 3 To prepare a saengjihwangja solution.

Example 12

In accordance with the prescription of ginseng paddoxane, which is stored in Dongbobogam, 125g each of ginseng, Siho, Jehoho, Ganghwa, Dokbok, Cheonggung, crust, Bokyeong, Gilgyeong, and licorice were weighed and processed according to the same method as in Example 3 to prepare ginseng padoxane solution. Was prepared.

Example 13

According to the prescription of Cheongan-tang, which was loaded in Dongbobogam, 188g of Peony Peony, 50g of Peel Bark, 125g of Cheongung and Angelica, 125g of Siho and 100g of Sanchi were weighed and processed according to the same method as in Example 3, and 75ml / bottle of Cheonggantang was prepared. 100 bottles of liquid solution were prepared.

Example 14

Stability was tested in the same manner as in Example 2 with each type of detergent prepared in Examples 3 to 13 being stored at 40 ° C. for 6 months. The results are shown in Table 3 below.

TABLE 3a

Preservation period composition (Example) Start of test 3 days 7 days 14 days 1 month 2 months 4 months 6 months 3 Sedimentation - - - - - - - - flavor Bitter little taste Bitter little taste Bitter little taste Bitter little taste Bitter little taste Bitter little taste Bitter little taste Bitter little taste 4 Sedimentation - - - - - - - + flavor Bitter little taste Bitter little taste Bitter little taste Bitter little taste Bitter little taste Bitter little taste Bitter little taste Bitter little taste

TABLE 3b

Preservation period composition (Example) Start of test 3 days 7 days 14 days 1 month 2 months 4 months 6 months 5 Sedimentation - - - - - - - - flavor Bitter little taste Bitter little taste Bitter little taste Bitter little taste Bitter little taste Bitter little taste Bitter little taste Bitter little taste 6 Sedimentation - - - - - - - + flavor Slightly bitter Slightly bitter Slightly bitter Slightly bitter Slightly bitter Slightly bitter Slightly bitter Slightly bitter 7 Sedimentation - - - - - - - - flavor Bitter little taste Bitter little taste Bitter little taste Bitter little taste Bitter little taste Bitter little taste Bitter little taste Bitter little taste 8 Sedimentation - - - - - - - - flavor Bitter little taste Bitter little taste Bitter little taste Bitter little taste Bitter little taste Bitter little taste Bitter little taste Bitter little taste 9 Sedimentation - - - - - - - - flavor Bitter little taste Bitter little taste Bitter little taste Bitter little taste Bitter little taste Bitter little taste Bitter little taste Bitter little taste 10 Sedimentation - - - - - - + + flavor Slightly bitter Slightly bitter Slightly bitter Slightly bitter Slightly bitter Slightly bitter Slightly bitter Slightly bitter 11 Sedimentation - - - - - - - + flavor Bitter little taste Bitter little taste Bitter little taste Bitter little taste Bitter little taste Bitter little taste Bitter little taste Bitter little taste 12 Sedimentation - - - - - - - + flavor Bitter little taste Bitter little taste Bitter little taste Bitter little taste Bitter little taste Bitter little taste Bitter little taste Bitter little taste 13 Sedimentation - - - - - - - - flavor Bitter little taste Bitter little taste Bitter little taste Bitter little taste Bitter little taste Bitter little taste Bitter little taste Bitter little taste

In Table 3,-means no occurrence of precipitation, and + means that it is visually identified when observed in detail that a small amount of precipitation has occurred.

As shown in Table 3, the results of the stability test for herbal medicines prepared by mixing 2 g of cyclodextrin solution and 0.5 g of poloxamer per 100 ml or 75 ml of a single dose to the prescription of various herbal medicines in synonym. , 5, 7, 8, 9 and 13 liquids did not produce precipitates even after 6 months storage at 40 ° C. and only after 4 months or 6 months at 40 ° C. in liquids of Examples 4, 6, 10 and 11 When observed closely with the naked eye, it could be observed that some precipitation was formed.

On the other hand, the bitterness and astringent taste in the various liquids tested were almost not seen in most cases even after 6 months at 40 ° C. from the start of the test, but only a slight bitter taste was detected in the liquid solutions of Examples 6 and 10. It can be seen that.

Therefore, according to the present invention, if the cyclodextrin liquid and the poloxamer of the herbal liquid are mixed at a predetermined ratio, it is possible to prevent the precipitation from occurring after the storage period has elapsed, thereby providing an improved effect on the storage stability, as well as the herbal medicine. It provides a pharmaceutical advantage that masks most of the inherent bitterness and taste so that it can be taken without reluctance.

Claims (5)

An herbal liquid characterized by containing a cyclodextrin liquid and a poloxamer. The herbal liquid preparation according to claim 1, wherein the cyclodextrin solution contains 0.1 to 5 w / v% and poloxamer 0.05 to 5 w / v%. The herbal solution according to claim 2, which contains 1 to 3 w / v% of cyclodextrin liquid and 0.1 to 1 w / v% of poloxamer. The cyclodextrin solution and poloxa according to claim 1, for the preparation of Hwanggi-tang, vigorous bleeding algae, Sangbaekpitang, Jaumyangyoungtang, Mundongumja, Chunhwasan, Okcheonsan, Hwangyeonjihwangtang, Saengjihwangja, ginseng paddoksan or Cheonggantang Herbal medicine characterized by the addition of a mer. The herbal medicine according to claim 4, wherein cyclodextrin liquid and poloxamer are added to the prescription of Hwanggi-tang.