KR100228752B1 - Liquid preparation containing insoluble biphenyldimethyldicarboxylate as active ingredient - Google Patents

Liquid preparation containing insoluble biphenyldimethyldicarboxylate as active ingredient Download PDF

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Publication number
KR100228752B1
KR100228752B1 KR1019970037233A KR19970037233A KR100228752B1 KR 100228752 B1 KR100228752 B1 KR 100228752B1 KR 1019970037233 A KR1019970037233 A KR 1019970037233A KR 19970037233 A KR19970037233 A KR 19970037233A KR 100228752 B1 KR100228752 B1 KR 100228752B1
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South Korea
Prior art keywords
ddb
diethylene glycol
water
monoethyl ether
monomethyl ether
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KR1019970037233A
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Korean (ko)
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KR19990015251A (en
Inventor
이한구
박영택
조진만
정상영
Original Assignee
김수지
대화제약주식회사
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/21—Esters, e.g. nitroglycerine, selenocyanates
    • A61K31/215—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids
    • A61K31/235—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids having an aromatic ring attached to a carboxyl group
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
    • A61K47/10—Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/08—Solutions

Abstract

본 발명은 물에 난용성인 DDB를 디에틸렌글리콜 모노메틸에테르, 디에틸렌글리콜 모노에틸에테르, 에틸렌글리콜 모노메틸에테르, 에틸렌글리콜 모노에틸에테르에서 선택한 1종 이상의 유기용매 및 물 또는 주사용 증류수에 용해시켜서 제조된 안정한 신규의 액상제제를 제공하는 것이며, 본 발명에 의하여 DDB의 안정한 액상제제가 개발되었다.The present invention is dissolved in a water-soluble DDB in at least one organic solvent selected from diethylene glycol monomethyl ether, diethylene glycol monoethyl ether, ethylene glycol monomethyl ether, ethylene glycol monoethyl ether and water or distilled water for injection It is to provide a stable new liquid formulation prepared, and a stable liquid formulation of DDB was developed by the present invention.

Description

난용성 약물인 비페닐디메틸디카르복실레이트를 주성분으로 함유하는 액제 및 그 제조방법Liquid formulation containing biphenyldimethyldicarboxylate, a poorly soluble drug, as a main component, and a method of manufacturing the same

본 발명은 난용성 약물인 비페닐디메틸디카르복실레이트를 주성분으로 함유하는 액상제제에 관한 것이다.The present invention relates to a liquid preparation containing biphenyldimethyldicarboxylate, which is a poorly soluble drug, as a main component.

비페닐디메틸디카르복실레이트(이하 "DDB"라 한다.)는 예로부터 한방에서 강장제 등으로 사용된 오미자에서 단리된 유효성분의 하나인 쉬잔드린(Schizandrin) C의 합성동족체로서 간염치료 뿐만 아니라, 간보호 작용도 있어, 현재 국내에서 널리 사용되고 있다. 그러나 DDB는 물에 난용성이며, 경구투여시 위장관에서의 분해는 매우 적지만 흡수가 매우 저조하여 약 5~30%만이 흡수되며 나머지는 배변으로 배출된다.Biphenyldimethyldicarboxylate (hereinafter referred to as "DDB") is a synthetic homologue of Shizandrin C, which is one of the active ingredients isolated from Schizandra chinensis used as a tonic, etc. Hepatoprotective action is also widely used in the country at present. However, DDB is poorly soluble in water, and during oral administration, it has very little degradation in the gastrointestinal tract, but its absorption is very low.

본 발명자들은 이러한 문제점을 해결하기 위하여 오랜 연구를 행한 결과, 본원발명에 따른 액상제제가, 현재 시판되는 DDB를 이용한 제제 즉, 정제, 캡슐제, 환제들에 비해 그 유효 함량만 투여하여도 될 뿐만 아니라, 응급시에 사용될 수 있고, 노약자가 경구 투여하기 어려 울 때에 주사제로도 사용될 수 있는 놀라운 사실을 발견하여 본 발명을 완성하였다.The present inventors have conducted a long study to solve these problems, and as a result, the liquid formulation according to the present invention may be administered only its effective amount compared to the formulation using commercially available DDB, that is, tablets, capsules, pills Not surprisingly, the present invention has been completed by discovering the surprising fact that it can be used in an emergency and can also be used as an injection when the elderly are difficult to orally administer.

지금까지 DDB의 통상적인 가용화방법은 폴리에틸렌글리콜과 글리세린의 혼합제, 또는 폴리소르베이트(트윈류) 등을 사용하여 제조하였으나, 이들은 주사제나 액제로 적용하기에는 점도상의 문제점과 적당량의 물을 가했을 때 DDB가 석출되는 관계로 이에 적용이 불가능하였다.Until now, the conventional solubilization method of DDB has been prepared using a mixture of polyethylene glycol and glycerin, or polysorbate (twins). However, they have a problem of viscosity and an appropriate amount of water when applied to injections or liquids. Due to precipitation, it could not be applied.

본 발명자들은 적당량의 물을 첨가하여도 침전이 석출되지 않아 주사제나 액제로의 적용이 가능하게 하여 약효가 신속하게 나타나는 DDB의 제제를 개발하여 본 발명을 완성하였다.The present inventors have completed the present invention by developing a formulation of DDB which does not precipitate even when an appropriate amount of water is added, so that it can be applied as an injection or a liquid, and the drug is rapidly exhibited.

본 발명자들은 디에틸렌글리콜 모노메틸에테르, 디에틸린글리콜 모노에틸에테르, 에틸렌글리콜 모노메틸에테르 및 에틸렌글리콜 모노에틸에테르에서 선택된 1종이상의 용매에 DDB를 용해시키고 여기에 필요하면 결정안정화제로 폴리에틸렌글리콜 300 - 400을 첨가하고 물을 가하여 용해시키면 DDB가 매우 잘 용해될 뿐만 아니라 장기간 저장하여도 결정이 석출되지 않는 놀라운 사실을 발견하여 본 발명을 완성하였다.The present inventors dissolve DDB in at least one solvent selected from diethylene glycol monomethyl ether, diethylglycol monoethyl ether, ethylene glycol monomethyl ether and ethylene glycol monoethyl ether, and if necessary, polyethylene glycol 300 as a crystal stabilizer. After adding 400 and dissolving with water, the present invention was completed by discovering the surprising fact that DDB not only dissolves very well but crystals do not precipitate even after long-term storage.

상기의 용제에 용해시에는 필요하면 아세톤을 소량 첨가하고 용해시킨 후 아세톤을 증발시켜서 제조할 수도 있다.When dissolving in the above solvent, if necessary, a small amount of acetone may be added, dissolved, and then prepared by evaporating acetone.

유기용매에 DDB를 용해시에는 필요하면 가온함이 바람직하다. 가온은 20 - 80℃까지가 바람직하다.When dissolving DDB in an organic solvent, it is preferable to warm if necessary. Heating is preferably up to 20-80 ° C.

DDB의 액상제제는 다음과 같은 조건을 만족하여야 한다.Liquid formulations of DDB should satisfy the following conditions.

첫째: 적당량의 물이 첨가되어도 DDB가 용액상태로 안정하여야 한다.First: DDB should be stable in solution even if the proper amount of water is added.

둘째: 액제의 경우 체내에서 신속히 약물을 방출하여야 하고 약물의 흡수가 잘 되어야 한다.Secondly, in the case of liquids, the drug must be released quickly and absorbed well.

셋째: 주사제의 경우 사용하기에 편리한 적정의 점도를 유지하여야 한다.Third, in the case of injections, the viscosity of the titration should be convenient.

본 발명의 액상제제는 상기의 조건을 모두 만족시킨다.The liquid formulation of the present invention satisfies all of the above conditions.

본 발명에서는 DDB의 양은 0.1 내지 20중량부를 사용하는 것이 바람직하다.In the present invention, the amount of DDB is preferably used 0.1 to 20 parts by weight.

본 발명에서는 유기용제는 10 내지 90중량부를 사용함이 바람직하다.In the present invention, it is preferable to use 10 to 90 parts by weight of the organic solvent.

본 발명에서는 정제수 또는 주사용정제수나 증류수는 10 내지 50중량부를 사용하는 것이 바람직하다.In the present invention, it is preferable to use 10 to 50 parts by weight of purified water, injectable purified water or distilled water.

다음의 실시예로써 본 발명을 상세히 설명하나, 본 실시예들이 본 발명의 범위를 한정하는 것은 아니다.The present invention will be described in detail with reference to the following examples, which are not intended to limit the scope of the invention.

[실시예 1]Example 1

디에틸렌클리콜 모노에틸에테르 500

Figure kpo00001
에 DDB 7.5
Figure kpo00002
을 녹인 후 물 300
Figure kpo00003
과 디에틸렌클리콜 모노에틸에테르 200
Figure kpo00004
을 가하여 교반하여 맑은 용액을 제조하였다.Diethylene glycol monoethyl ether 500
Figure kpo00001
DDB 7.5
Figure kpo00002
Melt water 300
Figure kpo00003
And diethylene glycol monoethyl ether 200
Figure kpo00004
It was added and stirred to prepare a clear solution.

[실시예 2]Example 2

에틸렌글리콜 모노에틸에테르 500

Figure kpo00005
에 DDB 7.5
Figure kpo00006
을 녹인 후 물 100
Figure kpo00007
과 에틸렌글리콜 모노에틸에테르 400
Figure kpo00008
을 가하여 교반하여 맑은 용액을 제조하였다.Ethylene Glycol Monoethyl Ether 500
Figure kpo00005
DDB 7.5
Figure kpo00006
Melt the water 100
Figure kpo00007
And ethylene glycol monoethyl ether 400
Figure kpo00008
It was added and stirred to prepare a clear solution.

[실시예 3]Example 3

디에틸렌글리콜 모노메틸에테르 500

Figure kpo00009
에 DDB 7.5
Figure kpo00010
을 녹인 후 물 300
Figure kpo00011
과 디에틸렌글리콜 모노에틸에테르 200
Figure kpo00012
을 가하여 교반하여 맑은 용액을 제조하였다.Diethylene glycol monomethyl ether 500
Figure kpo00009
DDB 7.5
Figure kpo00010
Melt water 300
Figure kpo00011
And diethylene glycol monoethyl ether 200
Figure kpo00012
It was added and stirred to prepare a clear solution.

[실시예 4]Example 4

디에틸렌클리콜 모노에틸에테르 500

Figure kpo00013
에 DDB 7.5
Figure kpo00014
을 녹인 후 물 200
Figure kpo00015
과 에틸렌글리콜 모노에틸에테르 300
Figure kpo00016
을 가하여 교반하여 맑은 용액을 제조하였다.Diethylene glycol monoethyl ether 500
Figure kpo00013
DDB 7.5
Figure kpo00014
Melt water 200
Figure kpo00015
And ethylene glycol monoethyl ether 300
Figure kpo00016
It was added and stirred to prepare a clear solution.

[실시예 5]Example 5

디에틸렌글리콜 모노에틸에테르 500

Figure kpo00017
에 DDB 7.5
Figure kpo00018
을 녹인후 폴리에틸렌글리콜#300 200
Figure kpo00019
과 혼합하고 물200
Figure kpo00020
을 가하고 다시 디에틸렌글리콜 모노메틸에테르를 100
Figure kpo00021
을 가하여 교반하여 맑은 용액상태로 제조하였다.Diethylene glycol monoethyl ether 500
Figure kpo00017
DDB 7.5
Figure kpo00018
After melting the polyethylene glycol # 300 200
Figure kpo00019
Mixed with water 200
Figure kpo00020
Add diethylene glycol monomethyl ether to 100
Figure kpo00021
It was added and stirred to prepare a clear solution.

[실시예 6]Example 6

디에틸렌글리콜 모노메틸에테르 500

Figure kpo00022
에 DDB 7.5
Figure kpo00023
을 녹인후 폴리에틸렌글리콜#300을 200
Figure kpo00024
을 가하고, 여기에 물 200
Figure kpo00025
을 가하고 다시 디에틸렌글리콜 모노메틸에테르 100
Figure kpo00026
을 가하여 교반하여 맑은 용액상태를 제조하였다.Diethylene glycol monomethyl ether 500
Figure kpo00022
DDB 7.5
Figure kpo00023
Melt the polyethylene glycol # 300 200
Figure kpo00024
Putting water here, 200
Figure kpo00025
Add diethylene glycol monomethyl ether 100
Figure kpo00026
It was added and stirred to prepare a clear solution.

[실시예 7]Example 7

디에틸렌글리콜 모노메틸에테르 500

Figure kpo00027
에 DDB 7.5
Figure kpo00028
을 녹인 후 주사용 증류수 300
Figure kpo00029
과 디에틸렌글리콜 모노메틸에테르 200
Figure kpo00030
을 가하여 교반한 다음 1
Figure kpo00031
용량의 앰플에 충진하고 멸균시켜서 주사제를 제조하였다.Diethylene glycol monomethyl ether 500
Figure kpo00027
DDB 7.5
Figure kpo00028
Dissolved in injection distilled water 300
Figure kpo00029
And diethylene glycol monomethyl ether 200
Figure kpo00030
Stir and add 1
Figure kpo00031
Injections were prepared by filling a dose of ampoules and sterilizing.

[실시예 8]Example 8

에틸렌글리콜 모토에틸에테르 500

Figure kpo00032
에 DDB 7.5
Figure kpo00033
을 녹인 후 주사용 증류수 100
Figure kpo00034
과 에틸렌글리콜 모노에틸에테르 400
Figure kpo00035
을 가하여 교반한 다음 1
Figure kpo00036
용량의 앰플에 충진하고 멸균시켜서 주사제를 제조하였다.Ethylene Glycol Mothethyl Ether 500
Figure kpo00032
DDB 7.5
Figure kpo00033
100 ml of distilled water for injection
Figure kpo00034
And ethylene glycol monoethyl ether 400
Figure kpo00035
Stir and add 1
Figure kpo00036
Injections were prepared by filling a dose of ampoules and sterilizing.

[실시예 9]Example 9

디에틸렌글리콜 모노메틸에테르 500

Figure kpo00037
에 DDB 7.5
Figure kpo00038
을 녹인 후 주사용 증류수 300
Figure kpo00039
과 디에틸렌글리콜 모노메틸에테르 200
Figure kpo00040
을 가하여 교반한 다음 1
Figure kpo00041
용량의 앰플에 충진하고 멸균시켜서 주사제를 제조하였다.Diethylene glycol monomethyl ether 500
Figure kpo00037
DDB 7.5
Figure kpo00038
Dissolved in injection distilled water 300
Figure kpo00039
And diethylene glycol monomethyl ether 200
Figure kpo00040
Stir and add 1
Figure kpo00041
Injections were prepared by filling a dose of ampoules and sterilizing.

[실시예 10]Example 10

디에틸렌글리콜 모노메틸에테르 500

Figure kpo00042
에 DDB 7.5
Figure kpo00043
을 녹인 후 주사용 증류수 200
Figure kpo00044
과 에틸렌글리콜 모노에틸에테르 300
Figure kpo00045
을 가하여 교반한 다음 1
Figure kpo00046
용량의 앰플에 충진하고 멸균시켜서 주사제를 제조하였다.Diethylene glycol monomethyl ether 500
Figure kpo00042
DDB 7.5
Figure kpo00043
Dissolved in distilled water for injection 200
Figure kpo00044
And ethylene glycol monoethyl ether 300
Figure kpo00045
Stir and add 1
Figure kpo00046
Injections were prepared by filling a dose of ampoules and sterilizing.

[실시예 11]Example 11

디에틸렌글리콜 모노에틸에테르 500

Figure kpo00047
에 DDB 7.5
Figure kpo00048
을 녹인후 폴리에틸렌글리콜#300 200
Figure kpo00049
, 주사용 증류수 200
Figure kpo00050
및 디에틸렌글리콜 모노에틸에테르 200
Figure kpo00051
을 가하여 교반한 다음 1
Figure kpo00052
용량의 앰플에 충진하고 멸균시켜서 주사제를 제조하였다.Diethylene glycol monoethyl ether 500
Figure kpo00047
DDB 7.5
Figure kpo00048
After melting the polyethylene glycol # 300 200
Figure kpo00049
, Distilled water for injection 200
Figure kpo00050
And diethylene glycol monoethyl ether 200
Figure kpo00051
Stir and add 1
Figure kpo00052
Injections were prepared by filling a dose of ampoules and sterilizing.

[실시예 12]Example 12

디에틸렌글리콜 모노에틸에테르 500

Figure kpo00053
에 DDB 7.5
Figure kpo00054
을 녹인후 폴리에틸렌글리콜#300 200
Figure kpo00055
, 주사용 증류수 200
Figure kpo00056
및 디에틸렌글리콜 모노메틸에테르 100
Figure kpo00057
을 가하여 교반한 후 1
Figure kpo00058
용량의 앰플에 충진하고 멸균시켜서 주사제를 제조하였다.Diethylene glycol monoethyl ether 500
Figure kpo00053
DDB 7.5
Figure kpo00054
After melting the polyethylene glycol # 300 200
Figure kpo00055
, Distilled water for injection 200
Figure kpo00056
And diethylene glycol monomethyl ether 100
Figure kpo00057
After adding and stirring 1
Figure kpo00058
Injections were prepared by filling a dose of ampoules and sterilizing.

[실험예 1]Experimental Example 1

효능실험 : 사염화 탄소로 유도된 간 장애에 대한 복강투여효과Efficacy test: intraperitoneal effect on carbon tetrachloride-induced liver disorders

(1) 실험동물(1) experimental animals

체중 120~150g 전후의 S.D계 음성 랫트 7마리씩 9군을 실험 시작 10시간 전부터 물만 주어 사육하였다.Nine groups of seven S.D-type negative rats at around 120-150 g body weight were fed with water only 10 hours before the start of the experiment.

(2) 실험방법(2) Experimental method

실험 동물은 7마리씩 9군으로 나누었다.Experimental animals were divided into 9 groups of 7 animals each.

제1군은 대조군으로 아무 처리 없이 사육하였다.The first group was raised as a control without any treatment.

제2군은 사염화탄소의 중독여부를 알기 위하여 사염화탄소를 콩기름에 용해하여 농도를 6.25％ (v/v)로 만든 액으로 체중

Figure kpo00059
당 1.25
Figure kpo00060
씩을 복강 주사하였다.The second group is a solution made by dissolving carbon tetrachloride in soybean oil to find out whether carbon tetrachloride is poisoned and making the concentration 6.25% (v / v).
Figure kpo00059
1.25 per
Figure kpo00060
Intravenous injections were done.

제3, 4, 5, 6, 7, 8군은 양성대조군으로 6.25％ 사염화탄소를

Figure kpo00061
당 1.25
Figure kpo00062
씩을 복강 주사하고 30분 경과한 후 실시예 1, 2, 3, 4, 5 및 6을 DDB로서 37.5
Figure kpo00063
해당량을 취하여 복강 주사하였다. 마찬가지로, 제 9군도 사염화탄소를
Figure kpo00064
당 1.25
Figure kpo00065
씩을 복강 주사한 후 30분 경과 후 DDB 37.5
Figure kpo00066
을 콩기름에 현탁하여 복강 주사하였다.The 3rd, 4th, 5th, 6th, 7th and 8th groups were positive control groups, which showed 6.25% carbon tetrachloride.
Figure kpo00061
1.25 per
Figure kpo00062
Example 1, 2, 3, 4, 5 and 6 as DDB 37.5 after 30 minutes elapsed intraperitoneally
Figure kpo00063
This amount was taken and intraperitoneally injected. Similarly, Group 9 also uses carbon tetrachloride.
Figure kpo00064
1.25 per
Figure kpo00065
30 minutes after intraperitoneal injection of DDB 37.5
Figure kpo00066
Was suspended in soybean oil and intraperitoneally injected.

18시간 경과 후 혈액을 취하여 s-GPT와 s-GOT를 측정하였다. 그 결과는 표 1과 같았다.After 18 hours, blood was taken to measure s-GPT and s-GOT. The results were shown in Table 1.

[표 1]TABLE 1

Figure kpo00067
Figure kpo00067

A : 대조군A: control group

B : 사염화 탄소 6.25％, 1.25

Figure kpo00068
B: carbon tetrachloride 6.25%, 1.25
Figure kpo00068

C : 사염화 탄소 6.25％, 1.25

Figure kpo00069
/
Figure kpo00070
+ 실시예 1C: carbon tetrachloride 6.25%, 1.25
Figure kpo00069
Of
Figure kpo00070
+ Example 1

D : 사염화 탄소 6.25％, 1.25

Figure kpo00071
/
Figure kpo00072
+ 실시예 2D: carbon tetrachloride 6.25%, 1.25
Figure kpo00071
Of
Figure kpo00072
+ Example 2

E : 사염화 탄소 6.25％, 1.25

Figure kpo00073
/
Figure kpo00074
+ 실시예 3E: carbon tetrachloride 6.25%, 1.25
Figure kpo00073
Of
Figure kpo00074
+ Example 3

F : 사염화 탄소 6.25％, 1.25

Figure kpo00075
/
Figure kpo00076
+ 실시예 4F: carbon tetrachloride 6.25%, 1.25
Figure kpo00075
Of
Figure kpo00076
+ Example 4

G : 사염화 탄소 6.25％, 1.25

Figure kpo00077
/
Figure kpo00078
+ 실시예 5G: carbon tetrachloride 6.25%, 1.25
Figure kpo00077
Of
Figure kpo00078
+ Example 5

H : 사염화 탄소 6.25％, 1.25

Figure kpo00079
/
Figure kpo00080
+ DDBH: carbon tetrachloride 6.25%, 1.25
Figure kpo00079
Of
Figure kpo00080
+ DDB

[실험예 2]Experimental Example 2

안정성에 대한 실험Experiment on stability

실시예 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 및 12의 액제 및 주사제를 실온에서 30일동안 방치하여 상태를 관찰하였으나, 침전이 생성된 것은 없었다.The solution and injection of Examples 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 and 12 were left at room temperature for 30 days to observe the condition, but no precipitate was formed.

따라서, 본 발명제의 액제는 매우 안정한 제제임이 확인된다.Therefore, it is confirmed that the liquid formulation of the present invention is a very stable formulation.

Claims (3)

물에 난용성인 DDB를 디에틸렌글리콜 모노메틸에테르, 디에틸렌글리콜 모노에틸에테르, 에틸렌글리콜 모노메틸에테르, 에틸렌글리콜 모노에틸에테르에서 선택된 1종 이상의 유기용매 및 물에 용해시켜서 제조된 액상제제.A liquid formulation prepared by dissolving DDB, which is poorly soluble in water, in at least one organic solvent selected from diethylene glycol monomethyl ether, diethylene glycol monoethyl ether, ethylene glycol monomethyl ether, and ethylene glycol monoethyl ether. 제 1항에 있어서, 안정화제로서 폴리에틸렌 글리콜 300-400을 가하여 제조된 액상제제.The liquid preparation according to claim 1, which is prepared by adding polyethylene glycol 300-400 as a stabilizer. 제 1항 또는 제 2항에 있어서, DDB이 양은 0.1 내지 20중량부, 디에틸렌글리콜 모노메틸에테르, 디에틸렌글리콜 모노에틸에테르, 에틸렌글리콜 모노메틸에테르 및 에틸렌글리콜 모노에틸에테르중에서 선택된 에테르계열 유기용매 10 내지 90중량부, 물 10 내지 50중량부를 가하여 제조된 액상제제.3. The ether-based organic solvent according to claim 1 or 2, wherein the amount of DDB is 0.1 to 20 parts by weight, diethylene glycol monomethyl ether, diethylene glycol monoethyl ether, ethylene glycol monomethyl ether and ethylene glycol monoethyl ether. A liquid formulation prepared by adding 10 to 90 parts by weight and 10 to 50 parts by weight of water.
KR1019970037233A 1997-08-04 1997-08-04 Liquid preparation containing insoluble biphenyldimethyldicarboxylate as active ingredient KR100228752B1 (en)

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* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
KR100391487B1 (en) * 2000-11-08 2003-07-16 주식회사 한국코러스제약 biphenyl dimethyl dicarboxylate composition for injections

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* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
KR970009803A (en) * 1995-08-29 1997-03-27 최수부 Pharmaceutical composition excellent in improving liver function and its preparation method

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* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
KR970009803A (en) * 1995-08-29 1997-03-27 최수부 Pharmaceutical composition excellent in improving liver function and its preparation method

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
KR100391487B1 (en) * 2000-11-08 2003-07-16 주식회사 한국코러스제약 biphenyl dimethyl dicarboxylate composition for injections

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