Use of opium antagonists for the manufacture of medicaments for controlling gastrointestinal dysmotility

[Table]

Placebo medication was stopped and the patient received the disposal of intravenous administration by Naloxson at the 2nd day and 4:00 p.m. based on the following schedule.

[Table]

Less than The dosing regime which stopped injection medication at 4:00 p.m. on the 3rd was changed into the oral method, and made synthetic grape juice put in and take in 3.6 mg of Naloxson every 3 hours for three days except for a patient's sleeping hours. A total given dose is 21.6 mg per day. She of the 5th day collected and measured feces during hospital stay. A result is shown below. Excrement stool volume (gram) Japanese wet weight Dry weight 1 452 41 2 649 52 3 985 77 4 997 77 5 806 65 A patient's blood and urinary samples were collected every day, and were given to analysis. Since the experiment as which the opposite effect was not regarded was conducted by the simple A blind method, the patient did not find a placebo (placebo) and an active ingredient, but took in it. EXAMPLE The 2nd patient is doing constipation of the more than past 20-year chronicity. A laxative was not useful, several months, a woman saved only by enema was sent to hospital, and dietary therapy with much Residual depended indigestiblely was given recently. Although it dealt with her like the patient of Example 1, neither a laxative nor intestines were given but were based on the following schedule. Day Disposal 1 Naloxson, 29.2 Mg, Vein 2 Placebo and Taking Orally 3 Naloxson, 14.4 Mg, Taking Orally 4 Naloxson, 21.6 Mg, Taking Orally 5 Naloxson, 21.6 Mg, Taking Orally 6 Naloxson, 7.2 Mg, Taking Orally 7 Placebo and Taking Orally 8 Placebo and Taking Orally 9 Placebo and Taking Orally The patient's feces were collected, were measured every day and obtained the following result.

[Table]

The opposite effect was not accepted by analysis of a clinical inspection, blood, or urine, either. the general procedure of example as well as -- therefore, a patient is added, the result of It was done disposal is summarized and the following table shows. The substantially same result is obtained with the compound of the range of Naruto Rexon, Nalmefuen, and the other present invention. Various lists show It was done, and the details and the result of some researches to the I was wrong. patient who worries about the intestines activity obstacle of various forms. For example, Table 1 shows the result related with the case which an inpatient and 2 times took lessons for five different Noodle inspections from the outpatient inner 3 time, and was carried out in the research hospital. Going over the 1st research in two days, the length of other researches is as record. The report of the 1st table to the 5th table is against the patient of chronic constipation. The thing to Patient in which the 6th, 7, and 8 table has intestines disease syndrome with a stimulus pain. The 9th and 10 table is a conclusion.

[Table]

5 - Usually -- Also Depending -- Poor [Table]

[Table]

[Table]

It returns to a connoisseur. 9 - - - - - Defecation with a finger is also impossible.

[Table]

3 Inside of a vein 1 Placebo - - - - (inpatient) 2 - 135 17 - Defecation with a finger. 3 Effective Compound 29.2 - - - 4 29.2 183 24 - Some feces was lost for the desire to have a bowel movement of a spontaneous defecation = suddenly.

[Table]

Was done. 5 - 554 26 - Those with an improvement. 6 - 114 9 - It is It was accompanied. about Difficulty to Defecation.

[Table]

Good. 3 placebo - 43 4.0 6.4 it durability-improves,; hurts and is --; -- usually -- also depending -- remarkable -- good.

[Table]

Inflation; a slight improvement. 9 -expansion; pain deemed; a slight improvement.

[Table]

See, it is and they are those with; expansion. 6 A little defecation of -2 time; those with pain-less; expansion.

[Table]

Placebo It carries out and is .. 7 Placebo - It is a nothing; common day in bowels. 8 - one defecation; -- usually -- a day -- Ri is also good. 9 - It is a nothing; common day in bowels.

[Table]

[Table]

The following form ration illustrates prescription which can be adopted in order to make the active ingredient of the present invention into various medication forms. The active ingredient in each form ration is Naloxson. Other compounds of Naruto Rexon, Nalmefuen, or the present invention can replace. Tablet Mg tablet 1 For Taking Orally : Naloxson Chloride Salt 12 Starch 50 Lactose 75 Stearic acid magnesium 2 Stearic acid 5 A small quantity of a drug object compound, starch, and lactose was mixed, and it Granulation(ed) with a starch paste. On a tray, the made Wet grain object is neglected by 45 degreeC overnight. The dry particles were powder-ized with the powder machine, and were taken as the powder of the size of about 20 meshes. The starch of stearic acid magnesium, stearic acid, and a required residue was added, all the ingredients before compressing by a tablet press were mixed, and it fabricated into a 232-mg tablet using 4 kg of balance, and 11 / 12'' punch. These tablets collapse by a half an hour by the method of a statement to USPXVI. Mg tablet 2 Naloxson 6 Micro crystallite cell rose 30 Spray dry lactose 60 Colloid silica 1 Stearic acid 1 Naloxson is screened, and a big and rough thing is removed, and it ranks next, and mixes with a micro crystallite cell rose. The lactose which carried out spray drying is added and it mixes. Finally stearic acid and colloid silica are added and it is made a homogeneous mixture. Subsequently, compression molding is carried out by 9/32 of thin bottom concave punches. Capsule 1 Naloxson Chloride Salt Ten Mg Lactose 45 Starch 45 A small quantity of a drug object compound, starch, and lactose was mixed, and it Granulation(ed) with a starch paste. On a tray, the made Wet grain object is neglected by 45 degreeC overnight. The dry particles are filled in the gelatin capsule of suitable size. 2 Naloxson 20 Mg Sesame oil After mixing sesame oil with 90 simple substances, the gelatin capsule of suitable size is stuffed. Gradual release continuation type 1 For Taking Orally The mother type (matrix) hydrophilic polymer which should be separated according to ingestion in the living body is made to include Naloxson (12 mg). Point One piece is melted in a suitable apolar solvent, and polymer is made to absorb this. If a solvent is removed, the product fixed in the mother type will be obtained and it will Release by solution. The speed of Release is governed by mother type hydrophilicity and a mother type can be made also possible [ biological collapse ] and impossible. 2 For Taking Orally Naloxson (12 mg) is mixed with Sik Lowe's, and 200 pellets through which it passes 1 m/m are built. 50 pieces are used in the form which does not carry out a coat. The remainder is classified three times, the coat of the adequate amount of stearic acid, pulmitic acid, and myristic acid glycerin ester is carried out, and it is made for the dissolution in intestines to take place in 4 and 8 or 12 hours. A bead is filled in a hard gelatin capsule. For parenteral 1 Mg/c.c. Naloxson chloride salt 10 methyl paraben 1.8 Propyl paraben 0.2 injection solvent Adequate amount Point Dissolution of the paraben is carried out into the heated injection solvent, and after cooling subsequently to room temperature, a combination thing and salt are dissolved. Subsequently, after letting the filter for microorganisms (0.6 micron or porosity not more than it) pass using sterilization art, it pours in to an ampul or the vial container for multi-time medication. Mg/c.c. 2 Naloxson 10 or 20 Ethanol 100 Propylene glycol 880 Naloxson is dissolved in alcohol, and it dilutes with propylene glycol, and makes solution. Subsequently, after letting the filter for microorganisms pass using sterilization art, it pours in to an ampul or the vial pint bottle for multiple medication. Gradual release continuation type 1 Parenteral Naloxson chloride salt (20 mg) is dissolved in the ethanol of an adequate amount. Sesame oil (5:1 ratios) is mixed with solution, and alcohol is removed by 45 * truth pressing down. A residue (what has a medicine in sesame oil) is moved to individual or the ampul for repeated dose. 2 Suppository Percent Naloxson chloride salt 4.06 polyoxy ethylene 1000 (about M1000) 80.14 Polyoxy ethylene 4000 (about M4000) 15.00 methyl paraben 45 Propyl paraben 05 pure water USP 3.10 Drug object chloride salt is melted in water, and it adds to the mixture of the polyoxy ethylene made together with paraben. This letter mixture of fusion is put in to a suppository fabrication metallic mold, and it molds into a 3 g/piece suppository. After solidifying, it packs with foil. 3 Tablet Naloxson chloride salt 10gm is mixed, 15% hydration propyl hydroxymethyl cell rose 65gm and polyethylene oxide (mW=5 millions) 24gm are made into uniform powdered slurry, and stearic acid Mg1mg is added. A mixture is pressed by pressure 100atm. 10 mg of Naloxson per tablet are contained. Cotton intermediary Naloxson is Release(ed) by internal use in 12 hours. 4 Tablet A 12-hour self-sustaining gradual release type Melmefuen tablet mixes 15% hydration propyl hydroxymethyl cell rose 63gm and polyethylene oxide (mW=5 millions) 24gm with Nalmefuen chloride salt 12gm by the conventional method, and makes them uniform powder slurry. This mixture is molded by 100atm pressure so that each tablet may contain 12 mg of Nalmefuen.