JP2003095935A - Medicinal composition administered via anus, rectum or vagina - Google Patents

Abstract

PROBLEM TO BE SOLVED: To obtain a medicinal composition exhibiting a marked effectiveness in hemorrhoids and vaginits which are difficult to be cured and different from a wound or an inflammation in the other mucous membranes or skin, since a local site suffered with hemorrhoids or vaginitis receives repeated physical or chemical irritations such as a severe friction, compression, osmotic difference in every time of defecation and urination, and is also exposed to the danger of bacterial infection. SOLUTION: This medicinal composition administered via the anus, rectum or vagina contains ecabet sodium and a medicinally permissible carrier and exhibits the marked effectiveness in hemorrhoids and vaginitis.

Description

Detailed Description of the Invention

[0001]

TECHNICAL FIELD The present invention relates to a pharmaceutical composition containing ecabet sodium for anal, rectal or vaginal administration, which can be used for treating hemorrhoids and vaginitis.

[0002]

BACKGROUND OF THE INVENTION Hemorrhoidal disease is a disease that develops in the anus or rectum and is roughly classified into hemorrhoids, anal fissures and anal fistulas, the symptoms of which are characterized by bleeding, pain, inflammation, swelling and itching. Although many medicines have been proposed in the past to treat or reduce the symptoms of hemorrhoids, they have a sufficient effect under the special circumstances of strong friction and pressure each time defecation occurs and bacterial infection is repeated. It is a very difficult and troublesome disease in terms of treatment, because it shows few drugs and the symptoms are temporarily disappeared or alleviated by surgical treatment but often recur. Vaginitis is inflammation of the vaginal epithelium and subcutaneous tissue, causing vaginal redness, swelling, pain, and increase in the amount of substantia. The cause of vaginitis is
There are pathogenic microorganisms such as Trichomonas protozoa, Candida, and Neisseria gonorrhoeae, which show unique pathological conditions. Even in the case of this vaginitis, urination exposes the affected area to physical and chemical irritation and bacterial infection in common with hemorrhoids. The chemical name of ecabet sodium is (+)-(1R, 4aS, 10aR) -1,
2,3,4,4a, 9,10,10a-octahydro-
1,4a-Dimethyl-7- (1-methylethyl) -6-
Sulfo-1-phenanthrenecarboxylic acid 6-sodium salt pentahydrate, gastric ulcer, gastric mucosal lesion, acute gastritis,
It is known as an oral preparation for treating gastritis and gastric ulcer that exerts a therapeutic effect on chronic gastritis (JP-A-58-77814).
It is also known to exert a therapeutic effect on pressure ulcer and wound healing agents (JP-A-10-338632).

[0003]

In the past, anti-inflammatory drugs, analgesics, local anesthetics, vasoconstrictors, mucosal protectants, astringents, etc. have been used alone or in combination for the treatment of hemorrhoids or vaginitis. However, there is no topical drug containing these components that cures hemorrhoids or vaginitis safely and effectively, and a safer and more effective topical drug has been desired.

[0004]

Means for Solving the Problems The present inventor has conducted diligent research to develop a topical preparation having few side effects and an excellent therapeutic effect on hemorrhoids and / or vaginitis. The inventors have found that hemorrhoids and vaginitis are extremely effectively cured by local administration of a composition containing the drug ecabet sodium as an active ingredient to the anus, rectum or vagina, and completed the present invention. That is, the present invention provides (1) a pharmaceutical composition for anal, rectal or vaginal administration, which comprises ecabet sodium and a pharmaceutically acceptable carrier,
(2) Containing 1 to 80% by weight of ecabet sodium (1)
The pharmaceutical composition described above, (3) further, an adrenocortical hormone agent,
Local anesthetic, antipyretic analgesic and anti-inflammatory agent, anti-inflammatory and anti-pruritic / wound healing agent,
(1) or (2) The pharmaceutical composition according to (1) or (2), which comprises one or more of vitamins, sulfa drugs, bactericides, vasoconstrictors, antihistamines, peripheral vasodilators, antidiarrheal / rectifying agents, (4) The pharmaceutical composition according to (1) or (2), wherein the pharmaceutical composition is for treating hemorrhoids or vaginitis, and (5) the pharmaceutical composition is a suppository, ointment, aerosol, solution, suspension, emulsion. The pharmaceutical composition according to any one of (1) to (4), which is a patch, poultice, liniment or lotion.

[0005]

BEST MODE FOR CARRYING OUT THE INVENTION The amount of ecabet sodium used in the present invention in a pharmaceutical composition is usually 1 to 80% by weight, preferably 10 to 60% by weight, more preferably 20% by weight.
~ 50% by weight. The dosage forms that the pharmaceutical composition of the present invention can take include suppositories, ointments, aerosols, solutions, suspensions, emulsions, patches, poultices, liniments, lotions and the like, but suppositories, A dosage form such as an ointment capable of accurately administering a fixed amount to the administration site is preferable. Each of these preparations can be produced according to a production method known per se.

[0006] Examples of the pharmaceutically acceptable carrier include an oily base and a water-soluble base. Examples of the oleaginous base include cacao butter, laurin fat, beef tallow, and hard fat derived from semi-synthetic products, which are solid at room temperature, or coconut oil or palm kernel oil which is liquid or semi-solid at room temperature. , Camellia oil, olive oil, soybean oil, sesame oil, corn oil, medium chain fatty acid triglyceride, liquid paraffin, white petrolatum, purified lanolin or isopropyl myristate or glyceryl monostearate, polyoxyethylene hydrogenated castor oil, sorbitan fatty acid ester, polyethylene glycol One or a combination of two or more surfactants such as fatty acid ester, polyoxyethylene sorbitan fatty acid ester, dextrin fatty acid ester and sucrose fatty acid ester, and higher alcohols such as stearyl alcohol and cetanol may be used. As long as it is acceptable for pharmaceuticals it is not limited to.

Examples of the water-soluble base include glycerin, polyethylene glycol, sorbitol, 1,3-
Butylene glycol, propylene glycol, ethanol, purified water and the like are conceivable, but not limited to these. If used as a suppository among these, it is preferably hard fat. As the ointment, white petrolatum, medium-chain fatty acid triglyceride and liquid paraffin are preferable.

The present invention includes a corticosteroid, a local anesthetic, an antipyretic analgesic / antiinflammatory agent, an antiphlogistic / antipruritic / wound healing agent, a vitamin agent, a sulfa drug, a bacterioconstrictor, an antihistamine, a peripheral vasodilator, and a stop agent. It is possible to mix one or more kinds of drugs used in the anti-diarrheal agent. In addition to the above-mentioned drugs, if necessary, additives such as an absorption promoter, a pH adjuster, a preservative, a dispersant, a wetting agent, a stabilizer, a preservative, a thickener, and a surfactant may be appropriately mixed. Good. In the pharmaceutical composition for topical administration of the present invention, the dose of ecabet sodium, which is the active ingredient, varies depending on the patient's symptoms, administration site, and dosage form, but cannot be generally stated.
Usually, in the case of hemorrhoids or vaginitis, about 50 to 1000 mg, preferably about 100 to 800 mg, is administered to the affected area about 1 to 3 times a day.

[0009]

EXAMPLES The present invention will be specifically described below with reference to examples and test examples. Example 1 Formulation (components and weight required for producing one suppository) Ecabet sodium 700 mg Hard fat 1050 mg Production method After dissolving hard fat at 50 ° C., ecabet sodium was added and dispersed therein, and then the suppository. Then, the suppository was manufactured by cooling it into a mold.

Example 2 Formulation (Ingredients and Weight Required to Produce One Suppository) Sodium Ecabet 350 mg Lidocaine 60 mg Tocopherol Acetate 60 mg Hard Fat 1280 mg Production Method Hard fat was melted at 60 ° C. and lidocaine and tocopherol acetate were added thereto. After dissolving and further dispersing by adding ecabetio sodium, the mixture was placed in a suppository mold and cooled to produce a suppository.

Example 3 Formulation (Ingredients and Weight Required to Produce One Suppository) Sodium Ecabet 700 mg Lidocaine 60 mg Prednisolone Acetate 1 mg Hard Fat 989 mg Production Method After dissolving hard fat at 60 ° C., lidocaine was dissolved in it. To this, prednisolone acetate and ecabet sodium were added and dispersed, and then placed in a suppository mold and cooled to produce a suppository.

Example 4 Formulation (ointment) Sodium ecabet 40 g Medium chain fatty acid triglyceride 10 g White petrolatum 57 g Manufacturing method Medium chain fatty acid triglyceride was heated to 60 ° C.
White vaseline heated to 0 ° C. was added to and mixed with each other, and sodium ecabet was further dispersed to produce an ointment.

Example 5 Formulation (ointment) Ecabet sodium 25 g Tribenoside 10 g Lidocaine 3 g Medium-chain fatty acid triglyceride 25 g White petrolatum 37 g Manufacturing method Medium-chain fatty acid triglyceride was heated to 60 ° C. and dissolved therein, and lidocaine and tribenoside were added. White vaseline heated to 60 ° C. was added and mixed, and sodium ecabet was further dispersed to produce an ointment.

Comparative Example 1 Formulation (Ointment) Medium-chain fatty acid triglyceride 10 g White vaseline 90 g Production method Medium-chain fatty acid triglyceride and white petrolatum were mixed at 60 ° C. to prepare an ointment.

Comparative Example 2 Formulation (Ingredients and Weight Required to Produce One Suppository) Hard Fat 1750 mg Production Method Hard fat was melted and then placed in a suppository mold and cooled to produce a suppository.

Test Example 1 The ointment of Example 4 and the ointment of Comparative Example 1 were applied to 3 hemorrhoids suffering from pain, discomfort and bleeding during defecation.
It was applied to the anus part once daily for 2 g, twice a day, and its therapeutic effect was observed. First, the ointment of Comparative Example 1 was administered for 7 days, but no improvement in pain, discomfort, and bleeding during defecation was observed. After that, when the ointment of Example 4 was administered for 7 days, the pain and discomfort at the time of defecation were remarkably reduced in 2 out of 3 subjects after 2 days had passed, and 3 out of 3 subjects had passed after 7 days had passed. Both the pain and discomfort during defecation completely disappeared. Regarding bleeding, in the patients to whom the ointment of Example 4 was administered, bleeding almost stopped 2 days after administration, and 3 out of 3 patients completely stopped bleeding after 7 days.

Test Example 2 Measurement of hyperemic inhibition rate using rat intestine 1. Rat intestinal ligation method A rat fasted for 12 hours was anesthetized with ether, and the abdomen about 1 cm from the lower end of the sternum was opened along the midline about 2 cm. The large intestine located on the dorsal side of the liver was ligated loosely so that the diameter of the intestinal tract was not widened so as not to suppress the movement of the intestine and to inhibit the passage of feces. The knot of the suture was adhered with an adhesive, the abdominal wall was sutured with 3 needles after intestinal ligation, and the epidermis was adhered with the adhesive. After the surgery, the rats were housed in separate cages until the test of the next day while allowing them to fast and drink freely. 2. Rats that had undergone intestinal ligation surgery on the day before perfusion of the anorectal region of the rat were held on a copper plate that had been passed through warm water at about 37 ° C for 30 minutes, and then the rectal temperature was measured to obtain 37.0 ± 0.3 ° C. Only the indicated solids were selected.
Various suppositories molded to a size of 150 mg were administered to the rectum of the selected rats, the anus was closed with clips, and the rats were retained on the copper plate described above. 5 minutes after administration of suppository, 10
After 30 minutes, 30 minutes, and 60 minutes, 50 mg / kg of sodium pentobarbital was intraperitoneally administered to each rat for anesthesia, the abdomen was opened, and a 14 G needle was inserted into the rectum approximately 1.5 cm from the vicinity of the pelvis. 0.45 mL of 0.125 N physiological saline was perfused from the needle tip at a flow rate of 0.5 mL / min, and at the same time, the anus was opened. Immediately after completion of the perfusion, the rat was exsanguinated to death, and the rectum including the anus was removed, attached to a cork plate, and photographed. 3. Calculation of the hyperemic inhibition rate From the photograph of the rectal anus taken, the hyperemic area and the non-equivalent area were separated, and the ratio of the non-equivalent area to the total rectal area was measured and used as the hyperemic inhibition rate. 4. Results Table 1 shows the change over time in the effect of suppressing hyperemia (n = 5).
As is clear from Table 1, the suppository of Example 1 showed a remarkable inhibition rate of hyperemia as compared with the suppository of Comparative Example 2.

[0018]

[Table 1]

[0019]

INDUSTRIAL APPLICABILITY The pharmaceutical composition for topical administration of the present invention, when administered to the anus, rectum or vagina, remarkably suppresses pain, discomfort and bleeding in a safe and fast manner.

─────────────────────────────────────────────────── ─── Continuation of front page (51) Int.Cl. ⁷ Identification code FI theme code (reference) A61K 9/12 A61K 9/12 9/70 401 9/70 401 A61P 9/08 A61P 9/08 15/02 15/02 17/00 17/00 F term (reference) 4C076 AA01 AA07 AA11 AA12 AA17 AA22 AA24 AA72 BB29 BB30 CC17 CC18 EE51A FF01 4C206 AA02 DA16 MA01 MA04 MA33 MA37 MA42 MA43 MA48 MA52 MA80 MA83 NA11 NA14 ZA89 ZA39 ZA39

Claims (5)

[Claims] 1. A pharmaceutical composition for anal, rectal or vaginal administration, comprising ecabet sodium and a pharmaceutically acceptable carrier. 2. The pharmaceutical composition according to claim 1, which contains 1 to 80% by weight of ecabet sodium. 3. A corticosteroid, a local anesthetic,
Antipyretic analgesic anti-inflammatory agent, anti-inflammatory anti-pruritic / wound healing agent, vitamin agent,
The pharmaceutical composition according to claim 1 or 2, comprising one or more of a sulfa drug, a bactericidal agent, a vasoconstrictor, an antihistamine, a peripheral vasodilator, and an antidiarrheal / intestinal preparation. 4. The pharmaceutical composition according to claim 1 or 2, which is used for treating hemorrhoids or vaginitis. 5. The pharmaceutical composition according to claim 1, which is a suppository, an ointment, an aerosol, a liquid, a suspension, an emulsion, a patch, a poultice, a liniment or a lotion. Pharmaceutical composition.