KR100461565B1 - Preparation of hydroxypropylmethyl cellulose - Google Patents
Preparation of hydroxypropylmethyl cellulose Download PDFInfo
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- KR100461565B1 KR100461565B1 KR10-2001-0058847A KR20010058847A KR100461565B1 KR 100461565 B1 KR100461565 B1 KR 100461565B1 KR 20010058847 A KR20010058847 A KR 20010058847A KR 100461565 B1 KR100461565 B1 KR 100461565B1
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- C08B—POLYSACCHARIDES; DERIVATIVES THEREOF
- C08B11/00—Preparation of cellulose ethers
- C08B11/02—Alkyl or cycloalkyl ethers
- C08B11/04—Alkyl or cycloalkyl ethers with substituted hydrocarbon radicals
- C08B11/08—Alkyl or cycloalkyl ethers with substituted hydrocarbon radicals with hydroxylated hydrocarbon radicals; Esters, ethers, or acetals thereof
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Abstract
본 발명은 저점도 히드록시프로필메틸 셀룰로오스의 제조방법에 관한 것으로서, 더욱 상세하게는 건조분말상의 중점도 히드록시프로필메틸 셀룰로오스를 산촉매로 가수분해하여 저점도 히드록시프로필메틸 셀룰로오스를 제조하는데 있어, 상기 가수분해 반응을 일정 압력, 온도범위에서 수행함으로써 산 촉매의 사용량을 최소화할 수 있고, 이때 얻어지는 저점도 히드록시프로필메틸 셀룰로오스를 다시 일정온도의 질소가스로 유동시킴으로써 최종제품의 황변현상과 잔류산의 양을 최소화하고 탄화물 생성 등의 부반응을 감소시켜 의약용으로 사용 가능한 점도범위를 갖는 저점도 히드록시프로필메틸 셀룰로오스의 제조방법에 관한 것이다.The present invention relates to a method for producing low viscosity hydroxypropyl methyl cellulose, and more particularly, to preparing low viscosity hydroxypropyl methyl cellulose by hydrolyzing a medium viscosity hydroxypropyl methyl cellulose on a dry powder with an acid catalyst. The amount of acid catalyst can be minimized by performing the hydrolysis reaction at a certain pressure and temperature range, and the yellowing phenomenon and residual acid of the final product can be reduced by flowing low viscosity hydroxypropylmethyl cellulose to nitrogen gas at a constant temperature. It relates to a method for producing low viscosity hydroxypropylmethyl cellulose having a viscosity range that can be used for medicine by minimizing the amount and reducing side reactions such as carbide production.
Description
본 발명은 저점도 히드록시프로필메틸 셀룰로오스의 제조방법에 관한 것으로서, 더욱 상세하게는 건조분말상의 중점도 히드록시프로필메틸 셀룰로오스를 산촉매로 가수분해하여 저점도 히드록시프로필메틸 셀룰로오스를 제조하는데 있어, 상기 가수분해 반응을 일정 압력, 온도범위에서 수행함으로써 산촉매의 사용량을 최소화할 수 있고, 이때 얻어지는 저점도 히드록시프로필메틸 셀룰로오스를 다시 일정온도의 질소가스로 유동시킴으로써 최종제품의 황변현상과 잔류산의 양을 최소화하고 탄화물 생성 등의 부반응을 감소시켜 의약용으로 사용가능한 점도범위를 갖는 저점도 히드록시프로필메틸 셀룰로오스의 제조방법에 관한 것이다.The present invention relates to a method for producing low viscosity hydroxypropyl methyl cellulose, and more particularly, to preparing low viscosity hydroxypropyl methyl cellulose by hydrolyzing a medium viscosity hydroxypropyl methyl cellulose on a dry powder with an acid catalyst. The amount of acid catalyst can be minimized by performing the hydrolysis reaction at a certain pressure and temperature range, and the yellowing phenomenon and the amount of residual acid in the final product can be obtained by flowing low viscosity hydroxypropylmethyl cellulose, which is obtained at this time, into nitrogen gas at a constant temperature. It relates to a method for producing low viscosity hydroxypropylmethyl cellulose having a viscosity range that can be used for medical purposes by minimizing and reducing side reactions such as carbide production.
일반적으로 저점도 히드록시프로필메틸 셀룰로오스는 주로 의약용으로 많이 사용되고 있으며, 그 용도로는 의약용 정제의 수분 침투 방지, 냄새 및 맛의 제거, 제품의 안정성 확보 등의 목적으로 사용되는 정제 코팅제와 최근에 광우병 파동으로 인한 젤라틴 캅셀의 대체용으로 사용되는 식물성 캅셀의 원료, 그리고 결합제,현탁제 등으로 널리 사용되고 있다. 이와같은 이유로 저점도 히드록시프로필메틸 셀룰로오스의 제조 방법은 많은 연구가 되어왔으며, 특히 의약용 분야에서 백색도, 강열잔분 함량 등 제품의 상품가치에 영향을 주는 요소의 개선이 중요한 관심사라 할 수 있다.In general, low-viscosity hydroxypropylmethyl cellulose is mainly used for medicinal purposes, and its use includes tablet coatings used for the purpose of preventing water penetration of medicinal tablets, removing odors and tastes, and securing product stability. It is widely used as a raw material of vegetable capsules used as a substitute for gelatin capsules caused by mad cow disease wave, and as a binder and suspending agent. For this reason, the preparation of low-viscosity hydroxypropylmethyl cellulose has been studied a lot, especially in the medical field, the improvement of factors that affect the product value of the product, such as whiteness, ignition residue content is an important concern.
중점도의 히드록시프로필메틸 셀룰로오스로부터 저점도의 히드록시프로필메틸 셀룰로오스를 제조하는 방법에 대해서는 많은 연구가 진행되고 있으며, 그 중에서도 히드록시프로필메틸 셀룰로오스를 구성하고 있는 글루코오스 분자 사이의 에테르 결합을 끊어 중합도를 감소시킴으로써 저점도의 히드록시프로필메틸 셀룰로오스를 얻는 방법이 널리 알려져 있다. 상기 방법은 중점도의 히드록시프로필메틸 셀룰로오스를 산촉매 하에서 가수분해함으로써 얻어지는데, 보통 건조 분말상의 중점도 히드록시프로필메틸 셀룰로오스에 염화수소 가스나 할로겐화 수소를 주입시켜 반응시키거나, 건조분말상의 중점도 히드록시프로필메틸 셀룰로오스를 회전식 믹서의 혼합 장치 내에서 불활성 유기용매를 이용하여 슬러리화하고 이를 할로겐화 수소가스 등의 산촉매로 가수분해시켜 저점도의 히드록시프로필메틸 셀룰로오스를 제조하는 방법 등이 널리 알려져 있다. 그러나, 산 촉매 존재 하에서 가수 분해하는 반응은 반응 후 최종제품에 황변현상 등이 발생하거나, 제품에 잔류하고 있는 잔류산이 보관 중 지속적으로 히드록시프로필메틸 셀룰로오스의 에테르 결합을 파괴해 시간이 지날수록 제품의 점도가 감소하는 등의 단점이 있다.Many studies have been conducted on the production of hydroxypropylmethyl cellulose having low viscosity from hydroxypropylmethyl cellulose having a medium viscosity, and among them, the degree of polymerization is achieved by breaking the ether bond between the glucose molecules constituting hydroxypropylmethyl cellulose. It is widely known to obtain low viscosity hydroxypropylmethyl cellulose by reducing The method is obtained by hydrolyzing hydroxypropylmethyl cellulose having a medium viscosity under an acid catalyst, and usually reacting by injecting hydrogen chloride gas or hydrogen halide into a medium powder hydroxypropyl methyl cellulose in a dry powder form, or having a medium strength hydrate in a dry powder A method of producing hydroxypropylmethyl cellulose having a low viscosity by slurrying oxypropylmethyl cellulose using an inert organic solvent in a mixing device of a rotary mixer and hydrolyzing it with an acid catalyst such as hydrogen halide gas is widely known. However, the hydrolysis reaction in the presence of an acid catalyst causes yellowing or the like in the final product after the reaction, or residual acid remaining in the product continuously destroys the ether bonds of hydroxypropylmethyl cellulose during storage. There are disadvantages such as a decrease in viscosity.
또 다른 저점도 히드록시프로필메틸 셀룰로오스의 제조방법은 공기나 과산화수소를 사용해 히드록시프로필메틸 셀룰로오스를 구성하고 있는 글루코오스 분자를직접 산화 반응시켜 글루코오스의 고리구조를 파괴함으로써 분자량을 감소시키는 방법이 있다. 상기 방법은 표백효과가 있는 장점이 있으나, 분자량을 대폭 감소시키고자 할 때에는 효과가 떨어지는 것이 일반적이다. 특히, 글루코오스 분자가 파괴됨으로써 제거할 수 없는 부산물이 생성됨으로써 다른 응용에 필요한 물성을 제대로 재현하지 못하는 등의 단점이 있다.Another method for producing low-viscosity hydroxypropylmethyl cellulose is to reduce the molecular weight by directly oxidizing the glucose molecules constituting the hydroxypropylmethyl cellulose using air or hydrogen peroxide to destroy the ring structure of glucose. Although the method has an advantage of having a bleaching effect, it is generally less effective when the molecular weight is to be greatly reduced. In particular, there is a disadvantage that the by-products that cannot be removed by the destruction of the glucose molecules are generated, so that the physical properties required for other applications cannot be properly reproduced.
이에 본 발명은 상기와 같은 문제점을 해결하기 위하여 건조분말상의 중점도 히드록시프로필메틸 셀룰로오스를 산촉매로 가수분해하여 저점도 히드록시프로필메틸 셀룰로오스를 제조하는데 있어, 상기 가수분해 반응을 일정 압력, 온도범위에서 수행하여 산촉매의 사용량을 최소화할 수 있고, 이때 얻어지는 저점도 히드록시프로필메틸 셀룰로오스를 다시 일정온도의 질소가스로 유동시킴으로써 최종제품의 황변현상과 잔류산의 양을 최소화하고 탄화물 생성 등의 부반응을 감소시켜 의약용으로 사용가능한 점도범위를 갖는 저점도 히드록시프로필메틸 셀룰로오스의 제조방법을 제공하는데 그 목적이 있다.In order to solve the problems described above, the present invention hydrolyzes a medium viscosity hydroxypropylmethyl cellulose on a dry powder with an acid catalyst to prepare a low viscosity hydroxypropylmethyl cellulose. The amount of acid catalyst used can be minimized, and the low-viscosity hydroxypropylmethyl cellulose obtained at this time is flowed to nitrogen gas at a constant temperature to minimize yellowing and residual acid in the final product, and side reactions such as carbide formation are performed. It is an object of the present invention to provide a method for preparing low viscosity hydroxypropylmethyl cellulose having a viscosity range that can be used for medical purposes by reducing the viscosity.
본 발명은 건조분말상의 중점도 히드록시프로필메틸 셀룰로오스를 산촉매로 가수분해하여 저점도의 히드록시프로필메틸 셀룰로오스를 제조하는 방법에 있어서, 상기 가수분해 반응은 산촉매하에서 질소가스를 이용하여 0.5 ∼ 2.0 atm로 가압하여 60 ∼ 75 ℃의 온도범위에서 가수분해 한 후에, 후처리공정으로 40 ∼ 60 ℃의 질소가스로 유동시키는 저점도 히드록시프로필메틸 셀룰로오스의 제조방법을 그 특징으로 한다.The present invention relates to a method for producing low viscosity hydroxypropylmethyl cellulose by hydrolyzing a medium-weight hydroxypropylmethyl cellulose in a dry powder with an acid catalyst, wherein the hydrolysis reaction is performed using nitrogen gas under an acid catalyst at 0.5 to 2.0 atm. It is characterized by a low viscosity hydroxypropylmethyl cellulose production method which is hydrolyzed at a temperature in the range of 60 to 75 ° C. and pressurized to 40 to 60 ° C. in a post-treatment step.
이와같은 본 발명을 더욱 상세히 설명하면 다음과 같다.Referring to the present invention in more detail as follows.
종래에는 건조분말상의 중점도 히드록시프로필메틸 셀룰로오스를 산촉매로 가수분해시켜 저점도 히드록시프로필메틸 셀룰로오스를 제조하였으나, 본 발명에서는 질소가스를 이용하여 0.5 ∼ 2.0 atm로 가압한 후 60 ∼ 75 ℃에서 3 ∼ 5 시간동안 가수분해 반응을 수행함으로써 산촉매의 사용량을 현격하게 줄일 수 있고, 후처리 공정으로 40 ∼ 60 ℃의 질소가스로 히드록시프로필메틸 셀룰로오스를 유동시키는 공정을 도입함으로써 부반응이 없어 최종제품의 황변현상과 제품내 잔류산의 양을 최소화시켜 제품의 점도를 일정하게 유지시켜 주는 특징이 있다.Conventionally, low viscosity hydroxypropylmethyl cellulose was prepared by hydrolyzing a medium-weight hydroxypropylmethyl cellulose in a dry powder with an acid catalyst, but in the present invention, pressurized to 0.5 to 2.0 atm using nitrogen gas at 60 to 75 ° C. By using the hydrolysis reaction for 3 to 5 hours, the amount of acid catalyst can be drastically reduced, and there is no side reaction by introducing a process of flowing hydroxypropylmethyl cellulose with nitrogen gas at 40 to 60 ° C. as a post-treatment process. It minimizes the yellowing phenomenon and the amount of residual acid in the product to keep the viscosity of the product constant.
본 발명에 사용된 중점도 히드록시프로필메틸 셀룰로오스는 셀룰로오스에 메틸클로라이드와 산화프로필렌을 반응시켜 얻어진 셀룰로오스 에테르로, 치환도 형태는 메톡실 함량이 28.0 ∼ 30.0%, 히드록시프로필 함량이 7.0 ∼ 12.0%인 한국약전에 명기된 2910타입의 제품이다. 중점도 히드록시프로필메틸 셀룰로오스는 0.5 ∼ 5%의 수분을 함유하고 있는 건조분말상으로, 2% 수용액에서의 점도가 20 ℃에서 약 50 ∼ 100 cps인 것을 사용할 수 있다. 본 발명은 상기 중점도의 히드록시프로필메틸 셀룰로오스를 3 ∼ 20 cps의 점도범위를 갖는 저점도 히드록시프로필메틸 셀룰로오스로 분해한다.The medium viscosity hydroxypropylmethyl cellulose used in the present invention is a cellulose ether obtained by reacting cellulose with methyl chloride and propylene oxide, and the degree of substitution is 28.0 to 30.0% of methoxyl content and 7.0 to 12.0% of hydroxypropyl content. It is a 2910 type product specified in the Korean Pharmacopoeia. The medium viscosity hydroxypropylmethyl cellulose is in the form of a dry powder containing 0.5 to 5% water, and a viscosity in a 2% aqueous solution can be used at about 50 to 100 cps at 20 ° C. The present invention decomposes hydroxypropylmethyl cellulose of the above-described midpoint into low viscosity hydroxypropylmethyl cellulose having a viscosity range of 3 to 20 cps.
본 발명에서는 산촉매로서 염화수소가스를 사용한다. 이러한 산촉매의양은 제조하고자하는 저점도 히드록시프로필메틸 셀룰로오스의 점도에 따라 선택적으로 사용할 수 있으며, 바람직하게는 중점도 히드록시프로필메틸 셀룰로오스 100 중량부에 대하여 0.15 ∼ 0.30 중량부로 사용하는 것이 좋다. 이때 산촉매의 사용량이 0.15 중량부 미만이면 가수분해 반응이 완전하게 이루어지지 않아 원하는 저점도 히드록시프로필메틸 셀룰로오스를 얻을 수 없고, 0.30 중량부를 초과하면 산촉매의 과다사용으로 인하여 최종제품에 황변현상이 발생하기 쉽다.In the present invention, hydrogen chloride gas is used as the acid catalyst. The amount of the acid catalyst may be selectively used depending on the viscosity of the low-viscosity hydroxypropylmethyl cellulose to be prepared, preferably 0.15 to 0.30 parts by weight based on 100 parts by weight of the medium viscosity hydroxypropylmethyl cellulose. At this time, if the amount of the acid catalyst is less than 0.15 parts by weight, the hydrolysis reaction may not be completed, and thus, the desired low viscosity hydroxypropylmethyl cellulose may not be obtained. If the amount of the acid catalyst exceeds 0.30 parts by weight, yellowing may occur in the final product due to excessive use of the acid catalyst. easy to do.
본 발명에서는 건조분말상의 중점도 히드록시프로필메틸 셀룰로오스를 상기와 같은 산촉매로 가수분해하는데 있어, 가수분해 반응을 질소가스를 이용하여 0.5 ∼ 2.0 atm의 압력범위에서 수행하는데 그 특징이 있다. 즉, 반응기내의 압력을 질소가스를 이용하여 0.5 ∼ 2.0 atm의 압력범위를 조절하여 줌으로써, 가수분해 반응 효율을 증가시켜 사용되는 산촉매의 양을 감소시킬 수 있다. 이때 만일 반응기내의 압력이 0.5 atm 미만이면 가압효과가 거의 나타나지 않고 히드록시프로필메틸 셀룰로오스의 점도가 높게 나오며, 2.0 atm을 초과하면 가수분해 반응이 잘 일어나지 않는 단점이 있다. 또한, 상기 가수분해 반응은 60 ∼ 75 ℃의 온도에서 3 ∼ 5 시간동안 진행되는데, 반응온도가 60 ℃ 미만이면 반응 시간이 길어지고 사용하는 산촉매의 양을 증량하여야 하는 문제가 있으며, 75 ℃를 초과하면 황변현상이 심해져 탄화물 발생량이 증가하게 되어 좋지 않다.In the present invention, in hydrolyzing a medium-weight hydroxypropylmethyl cellulose on a dry powder with an acid catalyst as described above, the hydrolysis reaction is carried out in a pressure range of 0.5 to 2.0 atm using nitrogen gas. That is, by adjusting the pressure in the reactor to the pressure range of 0.5 to 2.0 atm using nitrogen gas, it is possible to increase the hydrolysis reaction efficiency to reduce the amount of acid catalyst used. In this case, if the pressure in the reactor is less than 0.5 atm, the pressurizing effect is almost absent, and the viscosity of the hydroxypropylmethyl cellulose is high, and if the pressure exceeds 2.0 atm, the hydrolysis reaction does not occur well. In addition, the hydrolysis reaction proceeds for 3 to 5 hours at a temperature of 60 to 75 ℃, if the reaction temperature is less than 60 ℃ there is a problem that the reaction time is long and the amount of the acid catalyst to be used must be increased, 75 ℃ If exceeded, the yellowing phenomenon becomes severe and the amount of carbide generated is not good.
상기와 같은 가수분해 반응이 종료된 다음 제품에 소량으로 남아있는 산을 제거하기 위해 후처리 공정으로서 본 발명에서는 상기 반응이 완료된 히드록시프로필메틸 셀룰로오스를 유동층 건조기로 이송하여 40 ∼ 60 ℃의 질소가스로 30 ∼60분 동안 유동시킨다. 상기와 같이 산 제거후 소디움알칼리를 0.1 ∼ 0.2 중량부 유동층 건조기에 넣고 40 ∼ 60 ℃에서 30 ∼ 60분 동안 중화하여 pH 6 ∼ 8의 최종 저점도 히드록시프로필메틸 셀룰로오스를 얻을 수 있다. 상기와 같이 질소가스를 사용하면 종래에 비하여 잔류산을 최종 제품에서 최소화 할 수 있고, 제품의 점도를 일정하게 유지할 수 있다. 이때, 질소가스의 온도범위가 중요한 바, 상기 온도범위를 벗어나면 잔류산이 잘 제거되지 않는 문제가 있다.In the present invention as a post-treatment step to remove the acid remaining in the product in a small amount after the completion of the hydrolysis reaction as described above, the hydroxypropyl methyl cellulose is transferred to a fluidized bed dryer to nitrogen gas at 40 ~ 60 ℃ Furnace for 30 to 60 minutes. After removing the acid as described above, sodium alkali is added to a 0.1 to 0.2 part by weight fluidized bed drier and neutralized at 40 to 60 ° C. for 30 to 60 minutes to obtain a final low viscosity hydroxypropylmethyl cellulose having a pH of 6 to 8. Using nitrogen gas as described above can minimize the residual acid in the final product compared to the conventional, it is possible to maintain a constant viscosity of the product. At this time, the temperature range of the nitrogen gas is important, there is a problem that the residual acid is not removed well outside the temperature range.
이와같이, 본 발명에 따른 저점도 히드록스프로필메틸 셀룰로오스의 제조방법은 산촉매를 이용한 종래의 가수분해 제조방법에 있어 반응기내 압력을 질소가스를 이용하여 0.5 ∼ 2.0 atm의 압력범위로 조절하고, 후처리 공정으로 질소가스를 유동시킴으로써 산촉매의 사용량을 현격하게 감소시키고 이를 통해 최종 제품의 황변현상과 잔류산의 양을 최소화하여 의약용 저점도 히드록시프로필메틸 셀룰로오스의 제조에 매우 유용하다.As described above, the method for preparing low-viscosity hydroxypropylmethyl cellulose according to the present invention is a conventional hydrolysis production method using an acid catalyst, and the pressure in the reactor is adjusted to a pressure range of 0.5 to 2.0 atm using nitrogen gas, followed by post-treatment. Flowing nitrogen gas into the process significantly reduces the amount of acid catalyst used, thereby minimizing the amount of yellowing and residual acid in the final product, which is very useful for the preparation of medicinal low-viscosity hydroxypropylmethyl cellulose.
이와 같은 본 발명을 실시예에 의거하여 상세하게 설명하겠는 바, 본 발명이 실시예에 한정되는 것은 아니다.Although this invention is demonstrated in detail based on an Example, this invention is not limited to an Example.
실시예 1Example 1
250 kg의 히드록시프로필메틸 셀룰로오스(20 ℃, 2% 수용액의 점도 50 cps)를 설계압력 5 atm, 내벽이 유리로 코팅된 회전식 콘형 반응기에 넣고 반응기 내부에 있는 공기를 질소로 치환시켰다. 공기의 제거가 끝나면 10 rpm으로 회전식 콘형 반응기를 교반하면서, 유량조절기를 이용하여 600 g의 염화수소(0.24 중량부)가스를 천천히 주입하였다. 이때 반응기 내부의 압력은 0.1 atm 이하로 하였다. 염화수소 가스 주입이 완료되면 질소를 사용해 반응기 내부의 압력이 1 atm이 될 때까지 가압하였다. 가압이 끝나면 65 ℃로 승온하여 3시간 동안 반응시키고, 반응이 완료되면 반응기 내부의 질소와 염화수소 가스를 배출시키고, 유동층 건조기로 이송하여 제품내에 존재하는 잔류 염화수소가스를 60 ℃ 온도에서 30분 동안 제거하였다. 여기에 중화제인 소다회를 0.20 중량부 넣고 30분 동안 유동층에서 중화시켜 최종 저점도 히드록시프로필메틸 셀룰로오스를 얻었다.250 kg of hydroxypropylmethyl cellulose (at 50 ° C. in a 2% aqueous solution at 50 ° C.) was placed in a rotary cone reactor coated with a glass at 5 atm design pressure, and the inner wall was replaced with nitrogen. After the air was removed, 600 g of hydrogen chloride (0.24 parts by weight) gas was slowly injected using a flow controller while stirring the rotary cone reactor at 10 rpm. At this time, the pressure inside the reactor was 0.1 atm or less. When the hydrogen chloride gas injection was completed, the reactor was pressurized using nitrogen until the pressure inside the reactor became 1 atm. After pressurization, the temperature was raised to 65 ℃ to react for 3 hours, and when the reaction was completed, the nitrogen and hydrogen chloride gas in the reactor is discharged and transferred to the fluidized bed dryer to remove residual hydrogen chloride gas in the product at 60 ℃ temperature for 30 minutes It was. 0.20 parts by weight of soda ash, a neutralizing agent, was added thereto and neutralized in a fluidized bed for 30 minutes to obtain a final low viscosity hydroxypropylmethyl cellulose.
상기 저점도 히드록시프로필메틸 셀룰로오스는 2% 수용액의 점도가 20 ℃에서 6.2 cps이었다. 2% 점도는 모세관 형태의 Ubbelohde 점도계를 사용하여 측정하였다.The low viscosity hydroxypropylmethyl cellulose had a viscosity of 6.2 cps at 20 ° C. in a 2% aqueous solution. 2% viscosity was measured using a Ubbelohde viscometer in the form of capillary.
실시예 2Example 2
250 kg의 히드록시프로필메틸 셀룰로오스(20 ℃, 2% 수용액의 점도 50 cps)를 설계압력 5 atm, 내벽이 유리로 코팅된 회전식 콘형 반응기에 넣고 반응기 내부에 있는 공기를 질소로 치환시켰다. 공기의 제거가 끝나면 10 rpm으로 회전식 콘형 반응기를 교반하면서, 유량조절기를 이용하여 500 g의 염화수소(0.20 중량부) 가스를 천천히 주입하였다. 이때 반응기 내부의 압력은 0.1 atm 이하이었다. 염화수소 가스 주입이 완료되면 질소를 사용해 반응기 내부의 압력이 1 atm이 될 때까지 가압하였다. 가압이 끝나면 65 ℃로 승온하여 3시간 동안 반응시키고, 반응이 완료되면 반응기 내부의 질소와 염화수소 가스를 배출시키고, 유동층 건조기로 이송하여 제품내에 존재하는 잔류 염화수소가스를 60 ℃ 온도에서 30분 동안 제거하였다. 여기에 중화제인 소다회를 0.15 중량부 넣고 30분 동안 유동층에서 중화시켜 최종 저점도 히드록시프로필메틸 셀룰로오스를 얻었다.250 kg of hydroxypropylmethyl cellulose (at 50 ° C. in a 2% aqueous solution at 50 ° C.) was placed in a rotary cone reactor coated with a glass at 5 atm design pressure, and the inner wall was replaced with nitrogen. After the air was removed, 500 g of hydrogen chloride (0.20 parts by weight) gas was slowly injected using a flow controller while stirring the rotary cone reactor at 10 rpm. At this time, the pressure inside the reactor was 0.1 atm or less. When the hydrogen chloride gas injection was completed, the reactor was pressurized using nitrogen until the pressure inside the reactor became 1 atm. After pressurization, the temperature was raised to 65 ℃ to react for 3 hours, and when the reaction was completed, the nitrogen and hydrogen chloride gas in the reactor is discharged and transferred to the fluidized bed dryer to remove residual hydrogen chloride gas in the product at 60 ℃ temperature for 30 minutes It was. 0.15 parts by weight of soda ash, a neutralizing agent, was added thereto and neutralized in a fluidized bed for 30 minutes to obtain a final low viscosity hydroxypropylmethyl cellulose.
상기 저점도 히드록시프로필메틸 셀룰로오스는 2% 수용액의 점도가 20 ℃에서 14.7 cps이었다.The low viscosity hydroxypropylmethyl cellulose had a viscosity of 14.7 cps at 20 ° C. in a 2% aqueous solution.
실시예 3Example 3
250 kg의 히드록시프로필메틸 셀룰로오스(20 ℃, 2% 수용액의 점도 50 cps)를 설계압력 5 atm, 내벽이 유리로 코팅된 회전식 콘형 반응기에 넣고 반응기 내부에 있는 공기를 질소로 치환시켰다. 공기의 제거가 끝나면 10 rpm으로 회전식 콘형 반응기를 교반하면서, 유량조절기를 이용하여 500 g의 염화수소(0.20 중량부) 가스를 천천히 주입하였다. 이때 반응기 내부의 압력은 0.1 atm 이하이었다. 염화수소 가스 주입이 완료되면 질소를 사용해 반응기 내부의 압력이 1.5 atm이 될 때까지 가압하였다. 가압이 끝나면 65 ℃로 승온하여 3시간 동안 반응시키고, 반응이 완료되면 반응기 내부의 질소와 염화수소 가스를 배출시키고, 유동층 건조기로 이송하여 제품내에 존재하는 잔류 염화수소가스를 60 ℃ 온도에서 30분 동안 제거하였다. 여기에 중화제인 소다회를 0.15 중량부 넣고 30분 동안 유동층에서 중화시켜 최종 저점도 히드록시프로필메틸 셀룰로오스를 얻었다.250 kg of hydroxypropylmethyl cellulose (at 50 ° C. in a 2% aqueous solution at 50 ° C.) was placed in a rotary cone reactor coated with a glass at 5 atm design pressure, and the inner wall was replaced with nitrogen. After the air was removed, 500 g of hydrogen chloride (0.20 parts by weight) gas was slowly injected using a flow controller while stirring the rotary cone reactor at 10 rpm. At this time, the pressure inside the reactor was 0.1 atm or less. When the hydrogen chloride gas injection was completed, it was pressurized using nitrogen until the pressure inside the reactor became 1.5 atm. After pressurization, the temperature was raised to 65 ℃ to react for 3 hours, and when the reaction was completed, the nitrogen and hydrogen chloride gas in the reactor is discharged and transferred to the fluidized bed dryer to remove residual hydrogen chloride gas in the product at 60 ℃ temperature for 30 minutes It was. 0.15 parts by weight of soda ash, a neutralizing agent, was added thereto and neutralized in a fluidized bed for 30 minutes to obtain a final low viscosity hydroxypropylmethyl cellulose.
상기 저점도 히드록시프로필메틸 셀룰로오스는 2% 수용액의 점도가 20 ℃에서 12.3 cps이었다.The low viscosity hydroxypropylmethyl cellulose had a viscosity of 12.3 cps at 20 ° C. in a 2% aqueous solution.
실시예 4Example 4
250 kg의 히드록시프로필메틸 셀룰로오스(20 ℃, 2% 수용액의 점도 50 cps)를 설계압력 5 atm, 내벽이 유리로 코팅된 회전식 콘형 반응기에 넣고 반응기 내부에 있는 공기를 질소로 치환시켰다. 공기의 제거가 끝나면 10 rpm으로 회전식 콘형 반응기를 교반하면서, 유량조절기를 이용하여 500 g의 염화수소(0.20 중량부) 가스를 천천히 주입하였다. 이때 반응기 내부의 압력은 0.1 atm 이하로 하였다. 염화수소 가스 주입이 완료되면 질소를 사용해 반응기 내부의 압력이 0.5 atm이 될 때까지 가압하였다. 가압이 끝나면 65 ℃로 승온하여 3시간 동안 반응시키고, 반응이 완료되면 반응기 내부의 질소와 염화수소 가스를 배출시키고, 유동층 건조기로 이송하여 제품내에 존재하는 잔류 염화수소가스를 60 ℃ 온도에서 30분 동안 제거하였다. 여기에 중화제인 소다회를 0.15 중량부 넣고 30분 동안 유동층에서 중화시켜 최종 저점도 히드록시프로필메틸 셀룰로오스를 얻었다.250 kg of hydroxypropylmethyl cellulose (at 50 ° C. in a 2% aqueous solution at 50 ° C.) was placed in a rotary cone reactor coated with a glass at 5 atm design pressure, and the inner wall was replaced with nitrogen. After the air was removed, 500 g of hydrogen chloride (0.20 parts by weight) gas was slowly injected using a flow controller while stirring the rotary cone reactor at 10 rpm. At this time, the pressure inside the reactor was 0.1 atm or less. When the hydrogen chloride gas injection was completed, the reactor was pressurized with nitrogen until the pressure inside the reactor became 0.5 atm. After pressurization, the temperature was raised to 65 ℃ to react for 3 hours, and when the reaction was completed, the nitrogen and hydrogen chloride gas in the reactor is discharged and transferred to the fluidized bed dryer to remove residual hydrogen chloride gas in the product at 60 ℃ temperature for 30 minutes It was. 0.15 parts by weight of soda ash, a neutralizing agent, was added thereto and neutralized in a fluidized bed for 30 minutes to obtain a final low viscosity hydroxypropylmethyl cellulose.
상기 저점도 히드록시프로필메틸 셀룰로오스는 2% 수용액의 점도가 20 ℃에서 19.8 cps이었다.The low viscosity hydroxypropylmethyl cellulose had a viscosity of 19.8 cps at 20 ° C. in a 2% aqueous solution.
비교예 1Comparative Example 1
250 kg의 히드록시프로필메틸 셀룰로오스(20 ℃, 2% 수용액의 점도 50 cps)를 내벽이 유리로 코팅된 회전식 콘형 반응기에 넣고 10 rpm으로 회전식 콘형 반응기를 교반하면서, 유량조절기를 이용하여 750 g의 염화수소(0.30 중량부) 가스를천천히 주입하였다. 이때 반응기 내부의 압력은 0.1 atm 이하로 하였다. 염화수소 가스 주입이 완료되면, 65 ℃로 승온하여 3시간 동안 반응시켰다. 반응이 완료되면 반응기 내부의 질소와 염화수소 가스를 배출시키고, 유동층 건조기로 이송하여 제품내에 존재하는 잔류 염화수소가스를 60 ℃ 온도에서 30분 동안 제거하였다. 여기에 중화제인 소다회를 0.30 중량부 넣고 30분 동안 유동층에서 중화시켜 최종 저점도 히드록시프로필메틸 셀룰로오스를 얻었다.250 kg of hydroxypropylmethyl cellulose (at 20 ° C., a viscosity of 2% aqueous solution at 50 cps) was placed in a rotary cone reactor coated with an inner wall of glass, and the rotary cone reactor was stirred at 10 rpm, using 750 g of a flow controller. Hydrogen chloride (0.30 parts by weight) gas was slowly injected. At this time, the pressure inside the reactor was 0.1 atm or less. When hydrogen chloride gas injection was completed, the reaction mixture was heated to 65 ° C. for 3 hours. When the reaction was completed, the nitrogen and hydrogen chloride gas in the reactor was discharged and transferred to the fluidized bed dryer to remove residual hydrogen chloride gas present in the product at 60 ° C. for 30 minutes. 0.30 parts by weight of soda ash, a neutralizing agent, was added thereto and neutralized in a fluidized bed for 30 minutes to obtain a final low viscosity hydroxypropylmethyl cellulose.
상기 저점도 히드록시프로필메틸 셀룰로오스는 2% 수용액의 점도가 20 ℃에서 6.0 cps이었다.The low viscosity hydroxypropylmethyl cellulose had a viscosity of 6.0 cps at 20 ° C. in a 2% aqueous solution.
시험예Test Example
실시예 1 ∼ 4 및 비교예 1의 저점도 히드록시프로필메틸 셀룰로오스의 YI(Yellowness Index)와 잔류산의 양을 다음과 같은 방법으로 측정하였으며, 그 결과를 다음 표 1에 나타내었다.The YI (Yellowness Index) and the amount of residual acid of the low viscosity hydroxypropylmethyl cellulose of Examples 1 to 4 and Comparative Example 1 were measured by the following method, and the results are shown in Table 1 below.
<시험방법><Test method>
1. YI(Yellowness Index) : 2% 수용액의 YI를 Minolta 3700d 색도계를 사용하여 측정하였다.1. YI (Yellowness Index): The YI of 2% aqueous solution was measured using the Minolta 3700d colorimeter.
2. 잔류산의 양 : 염소이온농도 측정 방법인 Karl-Fischer방법을 사용하여 측정하였다.2. Amount of residual acid: measured using Karl-Fischer method, which is a method of measuring chlorine ion concentration.
상기 표 1에 나타난 바와 같이, 본 발명에 따른 저점도 히드록실프로필메틸 셀룰로오스는 YI값이 비교예 보다 작아 황변현상을 줄여 최종제품의 백색도를 향상시킴을 확인할 수 있으며, 또한 잔류산의 양이 2010 ppm 이하로 기존 반응 대비 매우 적음을 확인할 수 있었다.As shown in Table 1, the low-viscosity hydroxylpropylmethyl cellulose according to the present invention can be confirmed that the YI value is smaller than the comparative example to reduce the yellowing phenomenon to improve the whiteness of the final product, the amount of residual acid 2010 It was confirmed that it is very small compared to the existing reaction at less than the ppm.
상술한 바와 같이, 본 발명에 따른 저점도 히드록시프로필메틸 셀룰로오스의 제조방법은 산촉매를 이용한 종래의 가수분해 제조방법에 있어 상기 가수분해 반응을 질소가스를 이용하여 0.5 ∼ 2.0 atm의 압력범위에서 수행함으로써 산촉매의 사용량을 현격하게 감소시키고, 후처리 과정을 통해 최종제품의 황변현상과 잔류산의 양을 최소화하여 의약용 저점도 히드록시프로필메틸 셀룰로오스의 제조에 매우 유용하게 사용할 수 있다.As described above, the method for preparing low viscosity hydroxypropylmethyl cellulose according to the present invention is performed in the conventional hydrolysis production method using an acid catalyst in the pressure range of 0.5 to 2.0 atm using nitrogen gas. Therefore, the amount of acid catalyst is significantly reduced, and the yellowing phenomenon of the final product and the amount of residual acid are minimized through the post-treatment process, so that it can be very useful for the preparation of medicinal low viscosity hydroxypropylmethyl cellulose.
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| US461A (en) * | 1837-11-11 | Improvement in the method of constructing locks for fire-arms | ||
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| US3391135A (en) * | 1964-10-26 | 1968-07-02 | Shinetsu Chem Ind Co | Process for the manufacture of low molecular weight cellulose derivatives |
| US4061859A (en) * | 1976-06-14 | 1977-12-06 | The Dow Chemical Company | Viscosity reduction of cellulose derivatives |
| US4316982A (en) * | 1979-04-27 | 1982-02-23 | Hoechst Aktiengesellschaft | Process for reducing the viscosity of cellulose ethers by means of ozone and application thereof |
| EP0210917A2 (en) * | 1985-07-24 | 1987-02-04 | Shin-Etsu Chemical Co., Ltd. | A method for the preparation of a cellulose ether having a decreased degree of polymerization |
| EP0497985A1 (en) * | 1990-08-24 | 1992-08-12 | Shin-Etsu Chemical Co., Ltd. | Coating base for pharmaceutical film and production thereof |
| US6261218B1 (en) * | 1998-12-01 | 2001-07-17 | The Dow Chemical Company | Process and apparatus for making low molecular weight cellulose ethers |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US461A (en) * | 1837-11-11 | Improvement in the method of constructing locks for fire-arms | ||
| US1943461A (en) * | 1930-04-16 | 1934-01-16 | Ici Ltd | Cellulose ether and method of making same |
| US3391135A (en) * | 1964-10-26 | 1968-07-02 | Shinetsu Chem Ind Co | Process for the manufacture of low molecular weight cellulose derivatives |
| US4061859A (en) * | 1976-06-14 | 1977-12-06 | The Dow Chemical Company | Viscosity reduction of cellulose derivatives |
| US4316982A (en) * | 1979-04-27 | 1982-02-23 | Hoechst Aktiengesellschaft | Process for reducing the viscosity of cellulose ethers by means of ozone and application thereof |
| EP0210917A2 (en) * | 1985-07-24 | 1987-02-04 | Shin-Etsu Chemical Co., Ltd. | A method for the preparation of a cellulose ether having a decreased degree of polymerization |
| EP0497985A1 (en) * | 1990-08-24 | 1992-08-12 | Shin-Etsu Chemical Co., Ltd. | Coating base for pharmaceutical film and production thereof |
| KR950009102B1 (en) * | 1990-08-24 | 1995-08-14 | 신에쯔 케미칼 고오교 가부시끼가이샤 | Coating base for pharmaceutical film and production thereof |
| US6261218B1 (en) * | 1998-12-01 | 2001-07-17 | The Dow Chemical Company | Process and apparatus for making low molecular weight cellulose ethers |
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