JPH0368012B2 - - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION Field of the Invention The present invention relates to carminatives containing china oil or carminative formulations containing the active ingredients of such oils. The present invention provides a novel formulation for selectively administering the carminative into the intestine.

[Conventional technology and its problems]

Bowel disorders characterized by recurrent bowel dilatation, silicone colic, and intermittent changes in bowel habit are common. This is often referred to as irritable colon syndrome.
It is a diagnosis reached after excluding other organ pathologies.

Although this group of conditions may not be a single group based simply on one etiological factor, it is probably one of the most common clinical problems associated with disorders of the large intestine. The condition tends to recur and become chronic even after periods of normal health.

Irritable bowel syndrome and diverticular
Diseases and intestinal disorders such as spasmodic colon may be alleviated by administering muscle relaxants and/or antispasmodics to the intestines. However, there have been no completely satisfactory treatments for these disorders.
It is therefore an object of the present invention to provide relatively inexpensive, easily administered, and effective treatments for these disorders.

Peppermint oil is an ethereal oil obtained from the plant Labiatae and has been known as a drug since the very early days of pharmaceutical science. It has a mild stimulant effect on the mucous membranes of the mouth and gastrointestinal tract and is a mild expectorant.
In particular, it is used after meals as a carminative (i.e., a muscle relaxant with antispasmodic properties) and for the relief of gastric discomfort, flatulence, and to counteract the abdominal pain effects of laxatives. used (The Extra
(See Phamacopoeia 27th edition Martindale).

When administered for its known carminative properties, chivalry oil is taken orally to be effective in the stomach.
Its dosage is limited by the stimulant effect of the oil on the mucous membranes, especially on the gastro-oesophageal sphincter. Thus, the administered chile oil passes into the small intestine and sometimes into the colon. The amount is insufficient to produce any carminative effect in the intestine, and certainly not for effective treatment of irritable bowel syndrome, diverticular disease or spastic colon. To our knowledge, the possibility of using oil for the treatment of such intestinal disorders is limited due to the quantitative limitations imposed by its action on the esophageal and gastric mucosa and/or the gastro-esophageal sphincter. , perhaps it has been subconsciously abandoned. The truth of the matter is that our research shows that despite the long-known carminative properties of oil and the long-felt need for an immediately administered effective treatment for irritable bowel syndrome.
It has been found that there has been no proposal to use tsuka oil to induce carminative effects in the intestines.

[Means to solve problems]

We have found that china oil, when provided as an enteric coated gelatin capsule, provides an immediately administered and effective treatment for irritable bowel syndrome.

The present invention is an enteric preparation based on this knowledge, and is an enteric-coated capsule containing 0.05 to 0.5 ml of china oil per capsule.

Furthermore, the present invention is also a therapeutic agent for irritable bowel syndrome characterized by containing 0.05 to 0.5 ml of enteric-coated capsules per capsule.

The currently preferred Peppermint Oil (British Pharmacopoeia BP) is 4-10% w/w of esters calculated as methyl acetate, at least 44% w/w of free alcohol calculated as methanol and ketones calculated as menthone. Compounds 15-32% w/s
Contains. It is obtained by distillation and, if necessary, rectification, from the fresh flowering tops of the plant Menthe Piperita (Labiatae).

Enteric coatings are widely used in the pharmaceutical industry and are formed of substances that are relatively insoluble in the acidic medium of the stomach but disintegrate in the medium of the small intestine. The capsules are preferably hard gelatin capsules and a suitable enteric coating is a cellulose acetate phthalate coating. Other suitable coatings include enteric coating lacquers based on polymerized methacrylic esters.

Usually tsuka oil is administered in daily doses of 0.15 ml to 3.0 ml, especially 0.6 ml to 2.4 ml and especially about 1.2 ml.
The actual dosage will vary from patient to patient depending on, among other things, the identity of the chili oil, the patient's weight, tolerance to the chili oil, and the nature and extent of the disorder being treated. Each capsule contains 0.05ml-0.5ml, especially 0.15ml-
It contains 0.35ml, more preferably 0.3ml.

The following is a description, by way of example only, of presently preferred embodiments of the invention.

〔Example〕

Self-locking hard gelatin capsules (size 2; 0.37 ml) available as LOK-CAPS™ were manually filled with 0.15 ml of horsetail oil (British Pharmacopoeia) from an automatic pipette tube. The packed capsules were placed in a coating tower and placed in a stream of heated air (55°C) while the enteric coating solution was sprayed. The coating solution had the following weight composition:

Cellulose acetate phthalate 3% Diethyl phthalate 1% Liquid silicone (2000 c.s.) 1% Ethyl acetate 30% Acetone plus 100% (Specific gravity of solution 870 mg/ml. Solid content 5.5%) 43.01 ml per 100 capsules Theoretically, using the amount of 6
A coating of mg/cm ² was applied. It was in excess of the theoretically required amount to allow for losses during the coating process.

It will be appreciated that the above process is a small scale process designed to prepare several hundred capsules for clinical evaluation. Manufacturing scale processes will almost certainly differ both in the operations used and the relative proportions of the coating compositions.

The enteric coated capsules obtained as described above were subjected to a disintegration test for enteric coated tablets according to the 1973 British Pharmacopoeia (see page 123 of British Pharmacopoeia). Capsule 0.06N
It was immersed in hydrochloric acid for 3 hours, and no disintegration occurred during that time. However, all capsules disintegrated within 60 minutes when immersed in a standard solution of PH 6.8.

Enteric coated capsules were prepared as described above to assess in vivo disintegration, but filled with (a) the barium sulfate composition or (b) iodized poppy seed oil. Twelve randomly selected patients from a barium porridge clinic were each given two capsules of barium sulfate and two capsules of iodized poppy seed oil. The patient was examined radiologically. The average dissolution time was 143 minutes, and the dissolution site was in the small intestine.
The results show that the capsule passes through the stomach and most of the duodenum intact. Disintegration began at the end of the duodenum and continued into the jejunum, with the capsule initially releasing its contents along the entire length of the ileum. Thirty-two people at a colon clinic with symptoms consistent with irritable bowel syndrome voluntarily participated in an open clinical trial.
The dose used was one enteric-coated china oil capsule (prepared as described above, containing 0.15 ml of British Pharmacopoeia china oil) taken three times a day before meals. A pre-clinical evaluation of each patient was performed after the 14-day initial treatment period. If after this period no side effects were evident and the patient benefited from the treatment, it was continued for a further 14 days. After the second 14-day period, the overall patient response to the treatment was documented and compared to previous therapy. Treatment continued indefinitely if it was beneficial.

Thirteen patients had an excellent response and the other 12 patients had a good response. The treatment was not found to be beneficial for the remaining seven patients.

Only one patient showed signs of toxic effects, in the form of a hypersensitivity reaction to the menthol contained in the oil, which disappeared after the end of the treatment. Another patient with hydrochloric acid deficiency complained of heartburn and bloating. This was the result of the capsule disintegrating in the abnormally high pH of the hydrochloric acid-deficient stomach. Some patients who would benefit from this treatment have previously received diphenoxylate,
papverine, dicyclomine or mebeverine
was prescribed without success.

The results of the study showed that chives oil in enteric coated capsules is an acceptable and effective treatment for irritable bowel syndrome.

Claims (1)

[Scope of Claims] 1. Enteric-coated capsules containing a pharmacologically active ingredient, characterized in that the active ingredient is 0.05-0.5 ml of oil per capsule. Intestinal preparations. 2. The enteric preparation according to claim 1, wherein the enteric coating is a cellulose acetate phthalate coating. 3. The intestinal preparation according to claim 1 or 2, wherein the peppermint oil is Peppermint Oil of the British Pharmacopoeia (B, P,). 4. The intestinal preparation according to any one of claims 1 to 3, containing 0.15-0.35 ml of china oil per capsule. 5. The intestinal preparation according to claim 4, containing 0.2-0.3 ml of china oil per capsule. 6. A therapeutic agent for irritable colon syndrome, characterized in that each enteric-coated capsule contains 0.05-0.5 ml of oil.