The present invention relates to an enteric coating liquid, and more particularly to an aqueous enteric coating liquid containing an oxycarboxylic acid type cellulose derivative and enteric coated pharmaceuticals prepared by using the enteric coating liquid.
Hitherto, an enteric coating liquid has been prepared generally by dissolving in an organic solvent a high molecular substance which is insoluble in water and gastric juice, but soluble in intestinal juice, and adding, as occasion demands, a plasticizer, a coloring agent, etc. to the solution. However, the enteric coating according to such a process is economically disadvantageous, because a large quantity of an organic solvent is required in the preparation of the coating liquid and also the recovery of the solvent is difficult. Further, the use of the large quantity of the solvent causes problems such as safety to workers and danger due to ignition in the preparation of the enteric coating liquid and the pharmaceutical preparation, and safety to patients due to residual solvent in pharmaceuticals.
In recent years, recognition of the necessity for making the enteric coating liquid an aqueous system, namely for adopting a process using water as a dispersing medium, arose, and various processes have been proposed. However, the materials used for enteric coating are generally high molecular compounds having carboxyl groups which are difficult to form into an aqueous solution, because they are solubilized in water only in the form a salt in an alkaline water as a characteristic required for the enteric coating use.
Accordingly, there is little process put to practical use despite many proposals for preparing aqueous enteric coating liquids of high molecular compounds having carboxyl groups. The only one process practically adopted is a process using an aqueous emulsion of a methyl methacrylate/methacrylic acid copolymer prepared by emulsion polymerization. However, the preparation of aqueous enteric coating liquids according to this process is based on emulsion polymerization of acrylic monomers and, therefore, there is a possibility that a polymerization initiator, monomers, etc. remain and they cause a problem in safety for pharmaceutical use.
In such circumstances, as a process for preparing a completely aqueous enteric coating liquid by using high molecular compounds having carboxyl groups, there are known a process disclosed in Japanese Unexamined Patent Publication (Tokkyo Kokai) No. 7116/1976 wherein a high molecular compound is converted into a water-soluble salt, an aqueous solution thereof is coated on solid pharmaceuticals and the coated pharmaceuticals are treated with an acid to convert the salt into the original acid type high molecular compound; and a process disclosed in Japanese Examined Patent Publication (Tokkyo Kokoku) No. 12614/1981 wherein a dispersion of an enteric cellulose derivative powder having a particle size of not more than 100 .mu.m and a gelling agent having a boiling point of not less than 100.degree. C. in water is used for enteric coating. However, the former process has the disadvantages in that it is not suitable for coating pharmaceuticals unstable to acids and also, because of difficulty in completely converting the coating layer into the acid type, the first fluid resistance of the coating film, namely a resistance to a simulated gastric fluid which is saline water adjusted to a pH about 1.2 with hydrochloric acid, is insufficient. The latter process has the disadvantage that coating using a gear pump is difficult because of poor dispersion stability, as well as a problem that since the high molecular compound per se has no film forming property and requires a large quantity of a gelling agent, use of a plasticizer is necessary and, accordingly, there is a possibility of insufficient first fluid resistance.
An object of the present invention is to provide an aqueous enteric coating liquid containing a water-insoluble oxycarboxylic acid type cellulose derivative as a main component and having a good dispersion stability and a good film forming property, namely first fluid resistance.
Another object of the invention is to provide enteric coated pharmaceuticals covered with a continuous film formed from an aqueous coating liquid containing a water-insoluble oxycarboxylic acid type cellulose derivative as a main component.
These and other objects of the present invention will become apparent from the description hereinafter.
USPTO Backgrounds
USPTO Backgrounds