KR102346516B1 - Process for Preparing Crystal of Eldecalcitol - Google Patents

Process for Preparing Crystal of Eldecalcitol Download PDF

Info

Publication number
KR102346516B1
KR102346516B1 KR1020160155088A KR20160155088A KR102346516B1 KR 102346516 B1 KR102346516 B1 KR 102346516B1 KR 1020160155088 A KR1020160155088 A KR 1020160155088A KR 20160155088 A KR20160155088 A KR 20160155088A KR 102346516 B1 KR102346516 B1 KR 102346516B1
Authority
KR
South Korea
Prior art keywords
eldercalcitol
water
organic solvent
crystals
calcitol
Prior art date
Application number
KR1020160155088A
Other languages
Korean (ko)
Other versions
KR20180057017A (en
Inventor
이승종
신현익
이기영
오창영
Original Assignee
연성정밀화학(주)
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by 연성정밀화학(주) filed Critical 연성정밀화학(주)
Priority to KR1020160155088A priority Critical patent/KR102346516B1/en
Publication of KR20180057017A publication Critical patent/KR20180057017A/en
Application granted granted Critical
Publication of KR102346516B1 publication Critical patent/KR102346516B1/en

Links

Images

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C41/00—Preparation of ethers; Preparation of compounds having groups, groups or groups
    • C07C41/01—Preparation of ethers
    • C07C41/34—Separation; Purification; Stabilisation; Use of additives
    • C07C41/40—Separation; Purification; Stabilisation; Use of additives by change of physical state, e.g. by crystallisation
    • 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
    • A61K31/045—Hydroxy compounds, e.g. alcohols; Salts thereof, e.g. alcoholates
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C43/00—Ethers; Compounds having groups, groups or groups
    • C07C43/02—Ethers
    • C07C43/18—Ethers having an ether-oxygen atom bound to a carbon atom of a ring other than a six-membered aromatic ring
    • C07C43/196—Ethers having an ether-oxygen atom bound to a carbon atom of a ring other than a six-membered aromatic ring containing hydroxy or O-metal groups

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Epidemiology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Medicinal Chemistry (AREA)
  • Crystallography & Structural Chemistry (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

본 발명은 고순도의 엘더칼시톨 결정을 간단한 공정에 의해 제조하는 방법을 제공한다. The present invention provides a method for preparing high-purity eldercalcitol crystals by a simple process.

Description

엘더칼시톨 결정의 제조방법 {Process for Preparing Crystal of Eldecalcitol}Method for preparing eldercalcitol crystals {Process for Preparing Crystal of Eldecalcitol}

본 발명은 엘더칼시톨(Eldecalcitol) 결정의 제조방법에 관한 것으로, 보다 상세하게는 고순도의 엘더칼시톨 결정을 간단한 공정에 의해 제조하는 방법에 관한 것이다. The present invention relates to a method for producing eldercalcitol crystals, and more particularly, to a method for producing high-purity eldercalcitol crystals by a simple process.

하기 화학식 1의 엘더칼시톨((1R,2R,3R,5Z,7E)-2-(3-Hydroxypropyloxy)-9,10-secocholesta-5,7,10(19)-triene-1,3,25-triol)은 골다공증 치료제인 에디롤(Edirol®)의 활성 약학적 성분(API)이다.Elder calcitol of formula 1 ((1R,2R,3R,5Z,7E)-2-(3-Hydroxypropyloxy)-9,10-secocholesta-5,7,10(19)-triene-1,3, 25-triol) is an active pharmaceutical ingredient (API) of Edirol ®, an osteoporosis treatment.

[화학식 1][Formula 1]

Figure 112016113547811-pat00001

Figure 112016113547811-pat00001

미국 특허 제6,448,421호에는 엘더칼시톨 결정과 그의 제조방법이 개시되어 있으며, 특히 엘더칼시톨을 에틸아세테이트와 같은 유기용매를 이용하여 결정화할 수 있는 것으로 기재되어 있다. U.S. Patent No. 6,448,421 discloses elder calcitol crystals and a method for preparing the same, and in particular, it is described that elder calcitol can be crystallized using an organic solvent such as ethyl acetate.

그러나, 종래의 엘더칼시톨 결정의 제조방법에 의하면 결정화 용매로 사용된 에틸아세테이트가 약 1.24%(12,400 ppm) 정도 잔류되어 의약품 잔류용매 가이드 라인인 5,000 ppm을 크게 벗어나는 문제점을 가지고 있다.However, according to the conventional method for producing eldercalcitol crystals, about 1.24% (12,400 ppm) of ethyl acetate used as a crystallization solvent remains, which greatly deviates from the drug residual solvent guideline of 5,000 ppm.

미국 특허 제6,448,421호U.S. Patent No. 6,448,421

본 발명자들은 엘더칼시톨 결정의 제조에 있어서 상기한 문제점을 해결하고자 예의 연구 검토한 결과, 결정화 용매로서 물과 유기용매의 혼합용매를 사용하여 유기용매의 잔류량을 의약품 잔류용매 가이드 라인이 정하는 기준 이하로 조절할 수 있음을 알아내고, 본 발명을 완성하게 되었다. As a result of intensive research and review to solve the above problems in the manufacture of eldercalcitol crystals, the present inventors used a mixed solvent of water and organic solvent as a crystallization solvent, and the residual amount of organic solvent was determined by the guidelines for residual solvents in pharmaceuticals. It was found that it can be adjusted to the following, and the present invention was completed.

따라서, 본 발명의 목적은 고순도의 엘더칼시톨 결정을 간단한 공정에 의해 효율적으로 제조하는 방법을 제공하는 것이다.Accordingly, it is an object of the present invention to provide a method for efficiently preparing high-purity eldercalcitol crystals by a simple process.

본 발명의 일 실시형태는 엘더칼시톨 결정의 제조방법에 관한 것으로, 본 발명의 제조방법은 One embodiment of the present invention relates to a method for producing eldercalcitol crystals, the method of the present invention comprising:

(i) 엘더칼시톨을 물과 유기용매의 혼합용매에서 결정화하는 단계; 및(i) crystallizing eldercalcitol in a mixed solvent of water and an organic solvent; and

(ii) 생성된 엘더칼시톨 결정을 여과하는 단계를 포함한다.
(ii) filtering the resulting eldercalcitol crystals.

본 발명의 일 실시형태에서, 상기 유기용매는 아세토니트릴, 아세톤, 1,4-디옥산, 메탄올, 에탄올 및 이소프로판올로 구성된 군으로부터 선택된 하나 이상일 수 있으며, 특히 아세토니트릴일 수 있다.In one embodiment of the present invention, the organic solvent may be at least one selected from the group consisting of acetonitrile, acetone, 1,4-dioxane, methanol, ethanol and isopropanol, and in particular, acetonitrile.

본 발명의 일 실시형태에서, 상기 엘더칼시톨을 물과 유기용매의 혼합용매에서 결정화하는 단계는, 엘더칼시톨을 물과 유기용매의 혼합용매에 용해시킨 다음 상온에서 교반하여 수행하거나, 엘더칼시톨을 먼저 유기용매에 용해시키고 물을 천천히 가한 다음 상온에서 교반하여 수행될 수 있다. In one embodiment of the present invention, the step of crystallizing eldercalcitol in a mixed solvent of water and an organic solvent is performed by dissolving eldercalcitol in a mixed solvent of water and an organic solvent and then stirring at room temperature; Elder calcitol may be first dissolved in an organic solvent, water is slowly added, and then stirred at room temperature.

이때. 상기 유기용매와 물의 혼합비는 3:1 내지 1:3일 수 있다.At this time. A mixing ratio of the organic solvent and water may be 3:1 to 1:3.

본 발명의 일 실시형태에 따른 제조방법은 상기 상온 교반 후에 냉각하는 단계를 포함할 수도 있다. 이때, 냉각 온도는 -20 내지 20℃일 수 있다. The manufacturing method according to an embodiment of the present invention may include the step of cooling after stirring at room temperature. At this time, the cooling temperature may be -20 to 20 ℃.

본 발명의 일 실시형태에 따른 제조방법은 상기 단계 (ii)에서 여과된 엘더칼시톨 결정을 세척하고 건조하는 단계를 추가로 포함할 수 있다.
The manufacturing method according to an embodiment of the present invention may further include washing and drying the eldercalcitol crystals filtered in step (ii).

본 발명의 제조방법에 따라 결정화에 사용되는 엘더칼시톨은 상업적으로 입수하거나 당해 기술분야에서 공지된 방법에 의해 용이하게 제조할 수 있다.
Elder calcitol used for crystallization according to the preparation method of the present invention can be obtained commercially or can be easily prepared by a method known in the art.

본 발명의 일 실시형태에 따른 제조방법에 의해 제조된 엘더칼시톨 결정은 의약품 잔류용매 가이드 라인이 정하는 기준인 5,000 ppm 이하의 유기용매 잔류량을 가진다. Elder calcitol crystals prepared by the manufacturing method according to an embodiment of the present invention have an organic solvent residual amount of 5,000 ppm or less, which is a standard determined by the guidelines for residual solvents in pharmaceuticals.

또한, 본 발명의 일 실시형태에 따른 제조방법에 의해 제조된 엘더칼시톨 결정은 99% 이상의 순도를 가진다.In addition, the elder calcitol crystals prepared by the manufacturing method according to an embodiment of the present invention have a purity of 99% or more.

본 발명에 따르면, 결정화 용매로서 물과 유기용매의 혼합용매를 사용하여 엘더칼시톨에 잔류하는 유기용매의 잔류량을 의약품 잔류용매 가이드 라인이 정하는 기준 이하로 조절할 수 있고, 고순도의 엘더칼시톨 결정을 간단한 공정에 의해 제조할 수 있다.According to the present invention, by using a mixed solvent of water and an organic solvent as a crystallization solvent, the residual amount of the organic solvent remaining in eldercalcitol can be controlled below the standard set by the guidelines for residual solvents in pharmaceuticals, and high-purity eldercalcitol Crystals can be prepared by a simple process.

도 1은 실시예 1에서 제조된 엘더칼시톨 결정의 X선 분말 회절도이다.
도 2는 실시예 1에서 제조된 엘더칼시톨 결정의 단결정 X선 회절도이다.
도 3은 실시예 1에서 제조된 엘더칼시톨 결정의 열중량 분석도이다.
도 4는 실시예 1에서 제조된 엘더칼시톨 결정의 시차주사열량 분석도이다.1 is an X-ray powder diffraction diagram of eldercalcitol crystals prepared in Example 1.
FIG. 2 is a single crystal X-ray diffraction diagram of eldercalcitol crystals prepared in Example 1. FIG.
3 is a thermogravimetric analysis diagram of eldercalcitol crystals prepared in Example 1. FIG.
4 is a differential scanning calorimetry analysis diagram of elder calcitol crystals prepared in Example 1. FIG.

이하, 실시예에 의해 본 발명을 보다 구체적으로 설명하고자 한다. 이들 실시예는 오직 본 발명을 설명하기 위한 것으로 본 발명의 범위가 이들 실시예에 국한되지 않는다는 것은 당업자에게 있어서 자명하다.
Hereinafter, the present invention will be described in more detail by way of Examples. It is apparent to those skilled in the art that these examples are for illustrative purposes only, and the scope of the present invention is not limited to these examples.

비교compare 예Yes 1: 에틸아세테이트를 이용한 1: using ethyl acetate 엘더칼시톨의of elder calcitol 결정화 crystallization

순도 98% 이상인 무정형의 엘더칼시톨(1) (1.0 g)을 에틸아세테이트(10 ml)에 녹인 후, 실온에서 약 10 분 정도 교반하였다. 백색 고체가 생성되면 반응물의 온도를 0 ℃로 냉각하여 약 20 분 동안 교반하였다. 생성된 고체를 여과하고 차가운 에텔아세테이트(3 ml)로 세척하였다. 고체를 진공 중에 건조하여 에틸아세테이트의 잔류량이 12,400 ppm인 순도 99% 이상의 엘더칼시톨(1) (0.73 g, 73%)을 수득하였다.
Amorphous eldercalcitol (1) (1.0 g) having a purity of 98% or more was dissolved in ethyl acetate (10 ml), followed by stirring at room temperature for about 10 minutes. When a white solid was formed, the temperature of the reactant was cooled to 0 °C and stirred for about 20 minutes. The resulting solid was filtered and washed with cold ethyl acetate (3 ml). The solid was dried in vacuo to obtain eldercalcitol (1) (0.73 g, 73%) with a purity of 99% or more with a residual amount of ethyl acetate of 12,400 ppm.

실시예Example 1: One: 아세토니트릴과acetonitrile and 물의 혼합용매를 이용한 using a mixed solvent of water 엘더칼시톨의of elder calcitol 결정화 crystallization

순도 98% 이상인 무정형의 엘더칼시톨(1) (1.0 g)을 아세토니트릴 : 물 = 1 : 1 혼합용액(30 ml)에 녹인 후, 실온에서 약 30 분 정도 교반하였다. 백색 고체가 생성되면 반응물의 온도를 0 ℃로 냉각하여 약 30 분 내지 1 시간 동안 교반하였다. 생성된 고체를 여과하고 차가운 아세토니트릴 : 물 = 1 : 1 혼합용액(5 ml)으로 세척하였다. 고체를 진공 중에 건조하여 아세토니트릴의 잔류량이 410 ppm 이하인 순도 99% 이상의 엘더칼시톨(1) (0.80 g, 80%)을 수득하였다.Amorphous eldercalcitol (1) (1.0 g) having a purity of 98% or more was dissolved in an acetonitrile:water=1:1 mixed solution (30 ml), followed by stirring at room temperature for about 30 minutes. When a white solid was formed, the temperature of the reactant was cooled to 0 °C and stirred for about 30 minutes to 1 hour. The resulting solid was filtered and washed with a cold acetonitrile : water = 1 : 1 mixed solution (5 ml). The solid was dried in vacuo to obtain eldercalcitol (1) (0.80 g, 80%) having a purity of 99% or more with a residual amount of acetonitrile of 410 ppm or less.

수득한 엘더칼시톨의 X선 분말 회절분석, X선 단결정 회절분석, 열중량 분석 및 시차주사열량 분석을 수행하여, 그 결과를 각각 도 1 내지 도 4에 나타내었다.
X-ray powder diffraction analysis, X-ray single crystal diffraction analysis, thermogravimetric analysis, and differential scanning calorimetry analysis of the obtained eldercalcitol were performed, and the results are shown in FIGS. 1 to 4 , respectively.

실시예Example 2: 아세톤과 물의 혼합용매를 이용한 2: Using a mixed solvent of acetone and water 엘더칼시톨의of elder calcitol 결정화 crystallization

순도 98% 이상인 무정형의 엘더칼시톨(1) (40 mg)을 아세톤 : 물 = 1 : 1 혼합용액(1.2 ml)에 녹인 후, 실온에서 약 1 시간 동안 교반하였다. 생성된 고체를 여과하고 아세톤 : 물 = 1 : 1 혼합용액(1 ml)으로 세척하였다. 고체를 진공 중에 건조하여 아세톤 잔류량이 5,000 ppm 이하인 순도 99% 이상의 엘더칼시톨(1) (24 mg, 60%)을 수득하였다.
Amorphous eldercalcitol (1) (40 mg) having a purity of 98% or more was dissolved in an acetone:water=1:1 mixed solution (1.2 ml), followed by stirring at room temperature for about 1 hour. The resulting solid was filtered and washed with an acetone : water = 1 : 1 mixed solution (1 ml). The solid was dried in vacuo to obtain eldercalcitol (1) (24 mg, 60%) with a purity of 99% or more with a residual amount of acetone of 5,000 ppm or less.

실시예Example 3: 이소프로판올과 물의 혼합용매를 이용한 3: Using a mixed solvent of isopropanol and water 엘더칼시톨의of elder calcitol 결정화 crystallization

순도 98% 이상인 무정형의 엘더칼시톨(1) (40 mg)을 이소프로판올(0.6 ml)에 녹인 후, 물(1.8 ml)을 천천히 가하였다. 에멀젼 형태의 용액을 실온에서 1 시간 동안 교반하였다. 생성된 고체를 여과하고 이소프로판올 : 물 = 1 : 3 혼합용액(1 ml)으로 세척하였다. 고체를 진공 중에 건조하여 이소프로판올의 잔류량이 5,000 ppm 이하인 순도 99% 이상의 엘더칼시톨(1) (20 mg, 50%)을 수득하였다.
Amorphous eldercalcitol (1) (40 mg) having a purity of 98% or more was dissolved in isopropanol (0.6 ml), and then water (1.8 ml) was slowly added thereto. The solution in the form of an emulsion was stirred at room temperature for 1 hour. The resulting solid was filtered and washed with isopropanol : water = 1 : 3 mixed solution (1 ml). The solid was dried in vacuo to obtain eldercalcitol (1) (20 mg, 50%) with a purity of 99% or more with a residual amount of isopropanol of 5,000 ppm or less.

실시예Example 4: 에탄올과 물의 혼합용매를 이용한 4: Using a mixed solvent of ethanol and water 엘더칼시톨의of elder calcitol 결정화 crystallization

순도 98% 이상인 무정형의 엘더칼시톨(1) (40 mg)을 에탄올(0.6 ml)에 녹인 후, 물(1.0 ml)을 천천히 가하였다. 에멀젼 형태의 용액을 실온에서 1 시간 동안 교반하였다. 생성된 고체를 여과하고 에탄올 : 물 = 1 : 2 혼합용액(1 ml)으로 세척하였다. 고체를 진공 중에 건조하여 에탄올의 잔류량이 5,000 ppm 이하인 순도 99% 이상의 엘더칼시톨(1) (21 mg, 52.5%)을 수득하였다.
Amorphous eldercalcitol (1) (40 mg) having a purity of 98% or more was dissolved in ethanol (0.6 ml), and then water (1.0 ml) was slowly added thereto. The solution in the form of an emulsion was stirred at room temperature for 1 hour. The resulting solid was filtered and washed with a mixed solution of ethanol : water = 1 : 2 (1 ml). The solid was dried in vacuo to obtain eldercalcitol (1) (21 mg, 52.5%) with a purity of 99% or more with a residual amount of ethanol of 5,000 ppm or less.

실시예Example 5: 메탄올과 물의 혼합용매를 이용한 5: Using a mixed solvent of methanol and water 엘더칼시톨의of elder calcitol 결정화 crystallization

순도 98% 이상인 무정형의 엘더칼시톨(1) (40 mg)을 메탄올(0.6 ml)에 녹인 후, 물(0.4 ml)을 천천히 가하였다. 에멀젼 형태의 용액을 실온에서 1 시간 동안 교반하였다. 생성된 고체를 여과하고 메탄올 : 물 = 1 : 2 혼합용액(1 ml)으로 세척하였다. 고체를 진공 중에 건조하여 메탄올의 잔류량이 3,000 ppm 이하인 순도 99% 이상의 엘더칼시톨(1) (19 mg, 47.5%)을 수득하였다.
Amorphous eldercalcitol (1) (40 mg) having a purity of 98% or more was dissolved in methanol (0.6 ml), and then water (0.4 ml) was slowly added thereto. The solution in the form of an emulsion was stirred at room temperature for 1 hour. The resulting solid was filtered and washed with a methanol:water=1:2 mixed solution (1 ml). The solid was dried in vacuo to obtain eldercalcitol (1) (19 mg, 47.5%) with a purity of 99% or more with a residual amount of methanol of 3,000 ppm or less.

실시예Example 6: 1,4-디옥산과 물의 혼합용매를 이용한 6: Using a mixed solvent of 1,4-dioxane and water 엘더칼시톨의of elder calcitol 결정화 crystallization

순도 98% 이상인 무정형의 엘더칼시톨(1) (40 mg)을 1,4-디옥산(0.6 ml)에 녹인 후, 물(1.2 ml)을 천천히 가하였다. 에멀젼 형태의 용액을 실온에서 1 시간 동안 교반하였다. 생성된 고체를 여과하고 1,4-디옥산 : 물 = 1 : 2 혼합용액(1 ml)으로 세척하였다. 고체를 진공 중에 건조하여 1,4-디옥산의 잔류량이 380 ppm 이하인 순도 99% 이상의의 엘더칼시톨(1) (19 mg, 47.5%)을 수득하였다.Amorphous eldercalcitol (1) (40 mg) having a purity of 98% or more was dissolved in 1,4-dioxane (0.6 ml), and then water (1.2 ml) was slowly added thereto. The solution in the form of an emulsion was stirred at room temperature for 1 hour. The resulting solid was filtered and washed with a 1,4-dioxane:water=1:2 mixed solution (1 ml). The solid was dried in vacuo to obtain eldercalcitol (1) (19 mg, 47.5%) with a purity of 99% or more with a residual amount of 1,4-dioxane of 380 ppm or less.

Claims (8)

(i) 엘더칼시톨을 물과 유기용매의 혼합용매에서 결정화하는 단계; 및
(ii) 생성된 엘더칼시톨 결정을 여과하는 단계를 포함하고,
상기 단계 (i)에서, 유기용매와 물의 부피비가 3:1 내지 1:3인 엘더칼시톨 결정의 제조방법.(i) crystallizing eldercalcitol in a mixed solvent of water and an organic solvent; and
(ii) filtering the resulting eldercalcitol crystals;
In the step (i), the volume ratio of the organic solvent and water is 3:1 to 1:3 of the method for producing eldercalcitol crystals. 제1항에 있어서, 상기 유기용매는 아세토니트릴, 아세톤, 1,4-디옥산, 메탄올, 에탄올 및 이소프로판올로 구성된 군으로부터 선택된 하나 이상인 제조방법.The method according to claim 1, wherein the organic solvent is at least one selected from the group consisting of acetonitrile, acetone, 1,4-dioxane, methanol, ethanol and isopropanol. 제1항에 있어서, 상기 엘더칼시톨을 물과 유기용매의 혼합용매에서 결정화하는 단계는, 엘더칼시톨을 물과 유기용매의 혼합용매에 용해시킨 다음 상온에서 교반한 후에 -20 내지 20℃로 냉각하여 수행되는 제조방법.The method of claim 1, wherein in the step of crystallizing eldercalcitol in a mixed solvent of water and an organic solvent, eldercalcitol is dissolved in a mixed solvent of water and an organic solvent and then stirred at room temperature from -20 to 20 A manufacturing method carried out by cooling to ℃. 제1항에 있어서, 상기 엘더칼시톨을 물과 유기용매의 혼합용매에서 결정화하는 단계는, 엘더칼시톨을 먼저 유기용매에 용해시키고 물을 천천히 가한 다음 상온에서 교반하여 수행되는 제조방법.The method according to claim 1, wherein the step of crystallizing eldercalcitol in a mixed solvent of water and an organic solvent is performed by first dissolving eldercalcitol in an organic solvent, adding water slowly, and then stirring at room temperature. 삭제delete 제1항에 있어서, 상기 단계 (ii)에서 여과된 엘더칼시톨 결정을 세척하고 건조하는 단계를 추가로 포함하는 제조방법.The method according to claim 1, further comprising washing and drying the eldercalcitol crystals filtered in step (ii). 제1항에 있어서, 상기 엘더칼시톨 결정은 5,000 ppm 이하의 유기용매 잔류량을 가지는 제조방법.The method according to claim 1, wherein the elder calcitol crystals have an organic solvent residual amount of 5,000 ppm or less. 제1항에 있어서, 상기 엘더칼시톨 결정은 99% 이상의 순도를 가지는 제조방법.The method according to claim 1, wherein the elder calcitol crystals have a purity of 99% or more.
KR1020160155088A 2016-11-21 2016-11-21 Process for Preparing Crystal of Eldecalcitol KR102346516B1 (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
KR1020160155088A KR102346516B1 (en) 2016-11-21 2016-11-21 Process for Preparing Crystal of Eldecalcitol

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
KR1020160155088A KR102346516B1 (en) 2016-11-21 2016-11-21 Process for Preparing Crystal of Eldecalcitol

Publications (2)

Publication Number Publication Date
KR20180057017A KR20180057017A (en) 2018-05-30
KR102346516B1 true KR102346516B1 (en) 2022-01-03

Family

ID=62300505

Family Applications (1)

Application Number Title Priority Date Filing Date
KR1020160155088A KR102346516B1 (en) 2016-11-21 2016-11-21 Process for Preparing Crystal of Eldecalcitol

Country Status (1)

Country Link
KR (1) KR102346516B1 (en)

Families Citing this family (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN110204470A (en) * 2019-06-11 2019-09-06 南京海融医药科技股份有限公司 A kind of new crystal form and its preparation method and application of Chinese mugwort ground ostelin

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN106336369A (en) 2016-08-18 2017-01-18 上海皓元医药股份有限公司 Eldecalcitol crystal form and preparation method thereof

Family Cites Families (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
KR100554560B1 (en) * 1996-07-01 2006-05-25 쥬가이 세이야쿠 가부시키가이샤 Crystals of vitamin d derivatives and process for the preparation thereof
TWI247001B (en) 1996-07-01 2006-01-11 Chugai Pharmaceutical Co Ltd The method for purifying vitamin d derivatives and its crystalline products

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN106336369A (en) 2016-08-18 2017-01-18 上海皓元医药股份有限公司 Eldecalcitol crystal form and preparation method thereof

Also Published As

Publication number Publication date
KR20180057017A (en) 2018-05-30

Similar Documents

Publication Publication Date Title
KR100377159B1 (en) Method for preparing Form 2 of clarithromycin without residual solvent
US20180346506A1 (en) Method for preparing sofosbuvir crystal form-6
CN102659930B (en) High-purity cyclopeptide crystal and its preparation method and use
RU2354362C2 (en) Compositions of suberoylanilide-hydroxamic acid and methods of obtaining them
KR102346516B1 (en) Process for Preparing Crystal of Eldecalcitol
CN103819379A (en) Cholestanol co crystal of vitamin D3 and its preparation method and application
EP2621889B1 (en) Process for making fingolimod hydrochloride crystals
EP2658840B1 (en) Process for making fingolimod hydrochloride crystals
JP5090770B2 (en) Industrial production method of sarpogrelate hydrochloride
CN106866533B (en) Pyraclostrobin crystal form and preparation method thereof
JP2005053782A (en) New crystal of cyclic lipopeptide compound
EP0402806B1 (en) Crystalline cephem-acid addition salts and process for preparing them
AU2015206758B2 (en) Solid forms of tenofovir
EP3452446B1 (en) Process for the preparation cis-alkoxysubstituted spirocyclic 1-h-pyrrolidin-2,4-dione derivatives
CN104530112A (en) Method for preparing everolimus intermediate and ethylated impurities thereof
JP6761564B2 (en) L-proline compound of sodium-glucose cotransporter 2 inhibitor, and monohydrate and crystal of L-proline compound
CN105646521B (en) A kind of method for crystallising of moxidectin
RU2019106531A (en) Quinazoline derivative salt crystal
JPH11315088A (en) Fat soluble platinum (ii) complex hydrate
KR20180105450A (en) A Method of preparing Fimarsartan choline salt and hydrate thereof
CN110818817A (en) Sugammadex sodium diphenyl phosphine oxide derivative impurity and preparation method thereof
EP3002286B1 (en) Preparation method for polymorphic 6-(4-chlorophenoxy)-tetrazolo[5,1-a]phthalazine and use thereof
JP2018052931A (en) Solid phase forms of eldecalcitol
JP2010529094A (en) Direct dissolution of docetaxel in solvent in polysorbate 80
US20230286898A1 (en) Method for the purification of vilanterol trifenatate

Legal Events

Date Code Title Description
A201 Request for examination
E902 Notification of reason for refusal
E701 Decision to grant or registration of patent right
GRNT Written decision to grant