KR101241845B1 - Production of low molecular weight ethylcellulose - Google Patents

Abstract

Ethylcellulose having an ethoxyl content of 40 to 55% and a viscosity of 1 to 100 mPa · s as a 5% by weight solution of toluene to ethanol at a volume ratio of 80:20 at 25 ° C. has an ethoxyl content of 40 to 55% It is prepared by depolymerizing ethylcellulose having a viscosity of 4 to 400 mPa · s in the presence of gaseous hydrogen halide to reduce the viscosity of ethylcellulose by 10% or more.

Hydrogen halides, depolymerization, controlled drug release

Description

Production Method of Low Molecular Weight Ethyl Cellulose {Production of low molecular weight ethylcellulose}

The present invention relates to a process for the preparation of low molecular weight ethyl cellulose and to novel low molecular weight ethyl cellulose.

Ethylcellulose is useful in a wide range of industrial and pharmaceutical fields, such as printing inks, paper coatings, tablet binders, controlled drug release, and hydrophobic film formers.

Ethylcellulose chemically belongs to the class of cellulose ethers. Other well known cellulose ethers are methylcellulose, hydroxyethyl cellulose, hydroxypropyl cellulose, hydroxyethylmethyl cellulose, hydroxypropylmethyl cellulose and carboxymethyl cellulose, all classified as water soluble cellulose ethers by those skilled in the art. Methylcellulose and hydroxypropyl methylcellulose are well known for their insolubility in hot water and their water solubility in cold water. The preparation and end use of the cellulose ethers described above is tailored to the specific water solubility described above. High molecular weight methylcellulose and hydroxypropyl methylcellulose are generally alkalized high molecular weight cellulose pulp with alkali hydroxides, and then the alkalized cellulose is methylated, such as methyl chloride, in a gas phase or slurry process, and optionally hydroxypropionate, such as propylene oxide. Prepared by etherification with a deoxygenating agent to form high molecular weight cellulose ethers. When the etherification reaction is carried out as a slurry process, the reactant methyl chloride is usually used in excess and functions as a dispersion medium. The cellulose ethers prepared are generally washed with hot water to remove salts and other reaction byproducts, and to dry and mill. The molecular weight of the cellulose ethers described above can then be reduced by depolymerizing the cellulose ethers with hydrogen chloride and neutralizing the depolymerized cellulose ethers with a basic compound such as anhydrous sodium bicarbonate. Processes for depolymerization of cellulose ethers are described in US Pat. No. 3,391,135 and US Pat. No. 6,261,218.

Ethylcellulose has substantially different properties and behaves significantly different than the aforementioned water soluble cellulose ethers. According to Ullmann's Encyclopedia of Industrial Chemistry, ethylcellulose is water soluble at an ethyl degree of substitution (DS) value of 0.7 to about 1.7, which has an ethoxyl content of 17.4 to 36.5%. Corresponding to an organic soluble at a DS value greater than 1.5, which corresponds to an ethoxyl content of greater than 33.1%. Organic soluble ethylcellulose is thermoplastic and can be extruded into a plastic molding while retaining its mechanical properties under both water and low temperature conditions.

According to Uulman's Encyclopedia of Industrial Chemistry, the process for preparing ethyl cellulose is carried out as follows. "Ethyl chloride is used as the etherification agent. A temperature of about 110 ° C. is required and the reaction time is from 8 to 16 hours. Viscosity levels by aging alkali cellulose prior to the etherification reaction or controlling oxidation with air during the process. The efficiency of the etherification reaction, ie the fraction of ethyl chloride consumed that is converted into cellulose ether groups, increases with the concentration of NaOH used in the alkalizing reaction, generally using 55-76% NaOH solution. After the initial amount of NaOH has been consumed, solid alkali is added to the reaction weight to achieve good efficiency in a two step process. The salts are washed successively with water to remove from the crude product. "

It is well known to carry out the preparation of ethylcellulose described in Ullman's Encyclopedia of Industrial Chemistry in the presence of an organic solvent. According to the process described above, ethylcellulose having an ethoxyl content of 40 to 55% and a viscosity of about 10 mPa · s to about 400 mPa · s can be efficiently produced. Viscosity is measured at 25 ° C. as a 5% by weight solution in toluene to ethanol with a volume ratio of 80:20. At viscosities less than about 5 mPa · s, the water solubility of ethylcellulose is significantly increased, resulting in substantial product loss when washing crude product with water to remove salts. For example, when ethyl cellulose having an ethoxyl content of 40 to 55% and a viscosity of about 4 mPa · s is washed at 50 to 70 ° C., the product loss can be 20%. This is very disadvantageous because various grades of ethylcellulose are produced in thousands of tonnes per year in large scale manufacturing plants.

Accordingly, one object of the present invention is to provide a novel process for the efficient preparation of ethylcellulose having an ethoxyl content of 40 to 55%.

SUMMARY OF THE INVENTION

One aspect of the present invention is a process for producing ethylcellulose having an ethoxyl content of 40 to 55% and a viscosity of 1 to 100 mPa · s as a 5% by weight solution of toluene to ethanol at a volume ratio of 80:20 at 25 ° C. The method includes the step of depolymerizing ethylcellulose having an ethoxyl content of 40 to 55% and a viscosity of 4 to 400 mPa · s in the presence of gaseous hydrogen halide to reduce the viscosity of the ethylcellulose by at least 10%.

Another aspect of the present invention is the preparation (a) and preparation of ethylcellulose having an ethoxyl content of 40 to 55% and a viscosity of 4 to 400 mPa.s by etherification of alkalized cellulose with ethyl chloride in the presence of an organic solvent. Depolymerizing ethyl cellulose in the presence of gaseous hydrogen halide to reduce the viscosity of ethyl cellulose by more than 10% (b), wherein the ethyl cellulose has an ethoxyl content of 40 to 55% and a viscosity of 1 to 100 mPa · s. It is to provide a manufacturing method.

Yet another aspect of the invention is ethylcellulose, having an ethoxyl content of 40 to 55% and a viscosity of 1 to 2.5 mPa · s measured as a 5% by weight solution of toluene to ethanol at a volume ratio of 80:20 at 25 ° C. .

Surprisingly, it has been found that the method of the present invention can produce low molecular weight ethylcellulose in an efficient manner without excessive waste generation. Surprisingly, it has also been found that novel ethylcelluloses with very low molecular weight which could not be obtained using methods known in the art can be produced by the process of the invention.

Standard test methods for measuring the properties of ethylcellulose are described in ASTM D914-00 and the literature cited herein.

The method of the present invention produces low molecular weight ethylcellulose having an ethoxyl content of 40 to 55%, preferably 43 to 53%, more preferably 45 to 52%. Percent ethoxyl substitution is based on the weight of the substituted product and is measured according to the Zeisel gas chromatography technique as described in ASTM D4794-94 (2003). The above ethoxyl content corresponds to ethyl DS 1.9 to 3.0, preferably 2.1 to 2.9, more preferably 2.3 to 2.8.

The molecular weight of ethylcellulose is expressed as the viscosity of a 5% by weight solution of ethylcellulose measured at 25 ° C. in a mixture of 80% by volume toluene and 20% by volume ethanol. Ethylcellulose concentration is based on the total weight of toluene, ethanol and ethylcellulose. Viscosity is measured using an Ubbelohde tube as shown in ASTM D914-00 and further described in ASTM D914-00. The viscosity of ethylcellulose prepared according to the process of the present invention is generally from 1.0 mPa · s, preferably from 1.5 mPa · s, more preferably from 2.0 mPa · s to 100 mPa · s, preferably 50 mPa · s More preferably, up to 10 mPa · s, most preferably up to 7 mPa · s. Surprisingly, ethylcellulose having a viscosity of 4 mPa · s or less, most preferably 3 mPa · s or less, can be produced in an efficient manner without excessive waste generation. Ethyl cellulose having a viscosity of 1.0 to 2.5 mPa · s, preferably 1.0 to 2.3 mPa · s, more preferably 1.0 to 2.0 mPa · s is novel.

The starting materials used in the depolymerization step of the process of the invention have an ethoxyl content as mentioned above and have a viscosity of 4 to 400 mPa as measured at 25 ° C. as a 5% by weight solution of toluene to ethanol in a volume ratio of 80:20. s, Preferably it is 4-100 mPa * s, More preferably, it is 5-50 mPa * s, Most preferably, it is 7-20 mPa * s. In the depolymerization step in the process of the invention, the viscosity of the ethylcellulose is reduced by at least 10%, preferably at least 20%, more preferably at least 30%, based on the viscosity of the starting material used in the depolymerization step. Starting materials used for depolymerization can be prepared in a known manner by alkalizing cellulose pulp and etherifying the alkalized cellulose with ethyl chloride in the presence of an organic solvent. Alkalization of cellulose pulp is well known. Preferably sodium hydroxide is used. The molecular weight of the alkalized cellulose is preferably adjusted by aging the alkalized cellulose. The alkalized cellulose is then subjected to an organic solvent, preferably an aromatic hydrocarbon such as toluene or benzene, a C _1-6 alcohol such as ethanol; Mixtures of hydrocarbons such as toluene / ethanol mixtures with C _1-6 alcohols; Low molecular weight such as ethyl acetate or methyl acetate, preferably esters, ketones, or ethers having a molecular weight of 150 or less; Or ethyl chloride in a halogenated hydrocarbon, preferably a chlorinated hydrocarbon such as methylene chloride. The ethylation reaction of alkali cellulose is preferably carried out at 120 to 160 ° C, more preferably at 130 to 150 ° C for 6 to 10 hours, more preferably 7 to 9 hours. The reaction mixture is then cooled and generally ethanol is added to stop the etherification reaction. The reaction mixture prepared is generally subjected to a filtration step to remove some sodium chloride salts formed as by-products. The prepared ethylcellulose can be recovered from the reaction mixture by evaporation of the organic solvent. Further purification of ethylcellulose can be achieved by washing the ethylcellulose with water, preferably at 40 to 100 ° C, more preferably at 50 to 70 ° C. Purified ethylcellulose is preferably compressed into sheets and subsequently introduced into a grinding process known in the art. Ethylcellulose prepared according to the above process is commercially available from Dow Chemical Company. Various grades are commercially available under the trade name ETHOCEL and have a viscosity of 3 mPa · s to 385 mPa · s and an ethoxyl content of 45 to 52%.

The depolymerization of the invention is preferably carried out in the absence of reaction diluents. Preferably, undiluted ethylcellulose is contacted with gaseous hydrogen halide, more preferably gaseous hydrogen chloride, and most preferably anhydrous hydrogen chloride. Hydrogen chloride can be added directly to ethylcellulose or, preferably, directly to the headspace. The headspace can be purged with an inert gas such as nitrogen to prevent the combustion or ignition of ethylcellulose. Depolymerization temperature becomes like this. Preferably it is 50-110 degreeC, More preferably, it is 65-100 degreeC. The amount of gaseous hydrogen chloride is preferably 0.05 to 1%, more preferably 0.1 to 0.5%, based on the total weight of ethylcellulose to be polymerized.

If the water content at the start of the polymerization reaction is 0.5 to 5.0%, preferably 1.0 to 4.0%, more preferably 1.0 to 3.0%, most preferably 1.2 to 2.5% based on the total weight of dry ethylcellulose and water In addition, it has been found that the reaction rate can be increased and the discoloration of ethylcellulose during the depolymerization can be minimized. The water content is preferably controlled by controlling the water content of the ethylcellulose to be depolymerized, for example, by preparing the desired water content of ethylcellulose in the etherification and purification steps where the depolymerization proceeds, or by adding the desired amount of water prior to depolymerization. do. The duration of depolymerization depends on various factors, such as the viscosity of the starting material, the desired viscosity of the depolymerized product, the water content during the depolymerization and the temperature. Generally the depolymerization period is 1 to 12 hours, preferably 2 to 10 hours. Preferably, the presence of iron can promote depolymerization at the contact surface, which can lead to less constant depolymerization rates and the formation of carbonaceous tar, so ethylcellulose is not in contact with the iron containing surface during preparation or depolymerization. . Depolymerization can be stopped by cooling the reaction mixture, preferably below 40 ° C.

If desired, hydrogen halides such as hydrogen chloride can be removed from the depolymerized ethylcellulose, for example by stripping an inert gas such as nitrogen. Preferably, the depolymerized ethylcellulose is packaged after depolymerization without a neutralization step. Contamination with basic compounds can be avoided by avoiding the neutralization step prior to packaging depolymerized ethylcellulose for transport and use. Surprisingly, even though some or all of the hydrogen chloride used was still present in depolymerized ethylcellulose, it was found that the shelf life of depolymerized ethylcellulose was unexpectedly long. Over 4 months storage at 4 ° C., a viscosity drop of less than 1.5% of the final viscosity was observed.

Low molecular weight ethylcellulose is useful in a wide range of applications. Depolymerized ethylcellulose is preferably dissolved in the organic solvents described below for various end uses. Preferred field areas include the field of personal care, such as hair care, skin care or oral care; Or food, feed, agriculture or livestock. Ethylcellulose is useful for providing a hydrophobic film in personal care compositions, which is water resistant, increased wear resistance, and in antiperspirants, lipsticks, sunscreens, nail polishes, cosmetics, especially cosmetics, hair conditioners or oral care products designed to last long and Leads to improved delivery of water-insoluble active substances. In addition, low molecular weight ethylcellulose is useful as a thickener in the organic phase of, for example, oral care applications, perfumes, hair conditioners, water-in-oil emulsions, or aqueous emulsions.

The novel ethylcelluloses having an ethoxyl content of 40 to 55% and a viscosity of 1 to 2.5 mPa · s have significant advantages in various fields compared to known ethylcelluloses with high viscosity. The novel ethylcellulose has generally been found to have less nozzle agglomeration than known ethylcellulose, which has a high viscosity in spray drying techniques. Moreover, the novel ethylcellulose is soluble at higher concentrations in organic solvents than known ethylcellulose, which has a high viscosity. Examples of useful organic solvents include aromatic hydrocarbons such as toluene or benzene; C _1-6 alcohols such as ethanol or isopropanol; Other aliphatic alcohols such as octyl alcohol, cyclic alcohols such as methyl cyclohexanol; Mixtures of hydrocarbons with C _1-6 alcohols, such as toluene / ethanol mixtures; Esters such as ethyl acetate or n-butyl lactate; Ketones such as acetone, or ethers such as dioxane; Halogenated hydrocarbons, preferably chlorinated aliphatic and aromatic hydrocarbons such as methylene chloride chloride or monochlorobenzene; Or saturated cyclic hydrocarbons such as cyclohexane. In general, the novel ethylcellulose is also more soluble in the above-mentioned solvents (ie, higher concentrations of solutions can be obtained) or more readily soluble in water than known ethylcellulose having a high viscosity.

Due to the advantages mentioned above, the novel low-viscosity of the film or coating solution for providing various substrates such as oral solid dosage forms, feed, nutritional supplements, agricultural dosage forms, cleaning applications, deodorants, flavor enhancers, cosmetics or livestock applications Ethylcellulose is particularly useful. The spray ability of ethylcellulose at high polymer concentrations provides better water barrier properties and possibly slows down the active ingredient release. Thus, novel low viscosity ethylcellulose is very useful in the pharmaceutical field, especially in tablet coatings and drug controlled release films.

In addition, the nebulizing ability of low molecular weight ethylcellulose at high polymer concentrations and the rapid resolution of ethyl cellulose in organic solvents have been shown to reduce ethylcellulose to taste masking as a flavor fixative in oral solid dosage forms, liquid suspensions, feed, livestock applications and nutritional supplements. Makes it very useful. In addition, the benefits mentioned make ethylcellulose very useful in oral solid dosage forms, the livestock and agriculture sector, microencapsulation techniques for preparing food, feed, nutritional supplements and cosmetics. In addition, the advantages mentioned make ethylcellulose very useful as preparing granules or tablet binders for the abovementioned uses.

Moreover, the ethylcellulose of the present invention or prepared according to the present invention produces extruded films useful in the transdermal field, oral care, cheek side, wound care, food, feed or livestock fields, and the solid dosage forms into extruded films. Useful for application or extrusion spherical granulation. Ethylcellulose can be blended with one or more other polymers to produce extruded films.

Moreover, the ethylcellulose of the present invention or prepared according to the present invention may be used in various other fields, for example, inks such as packaging inks, conductive inks, inkjet inks, paste inks for printing circuit patterns; Electronic fields such as multilayer ceramic chips (MLCC), plasma display panels (PDP), liquid crystal displays (LCD); Varnishes such as batteries, fuel cells, ceramics, tough and long lasting surface finishes; Useful in rocket tapes, conductive pastes, fabric coatings, peelable coatings, paper coatings, lacquers or adhesives, especially hot melt adhesives.

The following examples are intended to illustrate the invention and not to limit the scope of the invention. Unless stated otherwise, all parts and percentages are parts by weight and weight percent. Unless stated otherwise, the viscosity is shown in ASTM D914-00 and further toluene in a volume ratio of 80:20 at 25 ° C. using an Uberdo tube as described in ASTM D446-04, which is further documented in ASTM D914-00. In a 5% by weight solution in ethanol.

Example 1

Powdered ethylcellulose commercially available from Dow Chemical Company under the trade name Etocel Standard 10 was used for depolymerization. Its ethoxyl content is 48.0 to 49.5% and the measured viscosity is 8.8 mPa · s. The water content of ethyl cellulose was adjusted to 2.0% of water based on the weight of wet ethyl cellulose. Ethylcellulose was placed in a vial and preheated to 90 ° C. in a lab oven. Anhydrous hydrogen chloride was then injected through the septum on top of the vial using a hypodermic needle, then the vial was shaken completely to ensure good distribution of hydrogen chloride through powdered ethylcellulose. The vial was then placed backwards in the lab oven. Hydrogen chloride was added 0.30% by weight based on the weight of ethyl cellulose. After a period of time, as shown in Table 1, the vial was removed from the oven and cooled in ice water to stop the reaction. The sample was then removed from the vial and dissolved in a mixture of toluene and ethanol at a volumetric ratio of 80:20 at a concentration of 5% by weight based on the total weight of toluene, ethanol and ethylcellulose. The viscosity of this solution was measured at 25 ° C. The results from general experiments are shown in Table 1.

Execution Reaction time (minutes) Final viscosity (mPas) 0 (comparison run) 8.8 1A 85 4.6 1B 110 4.2 1C 192 3.7 1D 204 3.0 1E 260 2.4 1F 372 1.8

The viscosity of ethylcellulose prepared according to Example IF was measured at 25 ° C. at various concentrations in various solvents using a Brookfield viscometer. The concentrations described are in weight units based on the total weight of the solution. The viscosity was obtained from Dow Chemical Company under the tradename Etocell Standard 4, having an ethoxyl content of 48.0-49.5% and a viscosity of 4.5 mPa · s measured as a 5% by weight solution of toluene to ethanol at a volume ratio of 80:20 at 25 ° C. The corresponding viscosity of commercially available powdered ethylcellulose was compared.

menstruum,
Concentration of ethyl cellulose Example IF
Viscosity of ethyl cellulose (mPas) Etocell Standard 4
Viscosity of ethyl cellulose (mPa.s) Ethanol, 10% 9.1 39.6 Ethanol, 30% 381 Not measured, gelled Toluene / ethanol ^* , 10% 6.2 26.4 Toluene / ethanol ^* , 30% 136 > 2,000 Toluene / ethanol ^* , 40% 893 > 2,000

* Toluene / ethanol at a volume ratio of 80:20

Table 2 shows that the novel ethylcellulose of the present invention can be dissolved in an organic solvent at a higher concentration than known ethylcellulose. Moreover, at high concentrations in various organic solvents, for example 10 or 30% by weight, the viscosity of ethylcellulose prepared according to Example IF was much lower than that of Etocell Standard 4. In addition, a solution of 30% ethylcellulose prepared according to Example IF in ethanol or toluene / ethanol blend was sprayable according to the known art, while a solution of 30% Etocell Standard 4 in the same solvent was not sprayable.

Examples 2-6

Example 1 was repeated except that Etocell Standard 20 with an ethoxyl content of 48.0-49.5% and a measured viscosity of 19.2 mPa · s was used for depolymerization. Moreover, the water content was adjusted as described in Table 3 below and the reaction time in each example was 60 minutes.

Example Water content during polymerization (%) Final viscosity (mPas) Undepolymerized
Starting material (comparative example) (Not depolymerized) 19.2 2 1.1 9.8 3 1.6 6.8 4 2.3 7.6 5 3.8 12.5 6 3.9 13.7

* Based on the weight of wet ethylcellulose.

Claims (13)

A process for preparing ethylcellulose having an ethoxyl content of 40 to 55% and a viscosity of 1 to 100 mPa · s as measured by a 5% by weight solution of toluene to ethanol at a volume ratio of 80:20 at 25 ° C., with an ethoxyl content of 40 to 55 Depolymerizing ethylcellulose having a viscosity of 4 to 400 mPa · s in the presence of gaseous hydrogen halide to reduce the viscosity of ethylcellulose by at least 10% and packaging the depolymerized ethylcellulose without neutralization after depolymerization, Method for preparing ethyl cellulose. The process for producing ethyl cellulose according to claim 1, wherein ethyl cellulose having an ethoxyl content of 40 to 55% and a viscosity of 1 to 10 mPa · s is produced. The process for producing ethyl cellulose according to claim 1 or 2, wherein the depolymerization is carried out in the presence of gaseous hydrogen chloride. The method of claim 1 or 2, wherein the depolymerization step is carried out in the presence of 0.5 to 5.0% of water, based on the total weight of dry ethylcellulose and water. The method of claim 1 or 2, wherein the depolymerization step is carried out in the presence of 0.1 to 0.5% by weight of hydrogen chloride based on the total weight of ethyl cellulose to be depolymerized. delete The process for producing ethyl cellulose according to claim 1 or 2, wherein ethyl cellulose having a viscosity of 4 to 100 mPa · s is depolymerized with ethyl cellulose having a viscosity of 1 to 2.5 mPa · s. A process for producing ethylcellulose having an ethoxyl content of 40 to 55% and a viscosity of 1 to 100 mPa · s as a 5% by weight solution of toluene to ethanol in a volume ratio of 80:20 at 25 ° C., Etherification of the alkalized cellulose with ethyl chloride in the presence of an organic solvent to produce ethylcellulose having an ethoxyl content of 40 to 55% and a viscosity of 4 to 400 mPa.s (a), (B) reducing the viscosity of ethylcellulose by at least 10% by depolymerizing the prepared ethylcellulose in the presence of gaseous hydrogen halide, and And (c) packaging the depolymerized ethyl cellulose without the neutralization step after depolymerization. delete delete delete delete delete