CN102114036A - New compound pantoprazole composite - Google Patents

Abstract

The invention relates to a new compound pantoprazole composite which takes pantoprazole, sodium bicarbonate and magnesium hydroxide as active ingredients according to the proportion of 1: 37.5: 17.15 or 2: 37.5: 17.15, wherein the pantoprazole comprises optical isomers and pharmaceutical salts of the pantoprazole. The composite can be combined with appropriate pharmaceutical excipients and prepared into oral preparations, such as tablets, capsules, chewable tablets and the like.

Description

A kind of new compound recipe pantoprazole compositions

Technical field

The present invention is a kind of new compound recipe pantoprazole compositions, belongs to medical technical field.

Background technology

Pantoprazole is a kind of proton pump inhibitor behind omeprazole, this type of medicine easily enters acid parietal cell, to H+, the K+-ATP enzyme has the high selectivity inhibitory action, and the ratio that is activated under neutral and weak acid environment is minimum, and character is more stable, activation rapidly under strong acidic condition, the activation characteristic that its pH relies on makes its effect to H+, K+-ATP enzyme have better choice, is a class medicine of at present the strongest treatment gastric acid secretion.

Sodium bicarbonate is a weak base, is systemic antacid.In the energy and gastric acid, dissolving mucus reduces the viscosity of Digestive system, and strengthens gastrointestinal and shrink, and plays and is good for the stomach, presses down acid and orectic effect.Normal and other antacid are together taken, and play the synergic effect of mutual coordination.

Magnesium hydroxide is a kind of gastric mucosa protectant, oral after the rapid gel of layer overlay fruit jelly sample on gastric mucosa, thereby the protection gastric mucosa, in and gastric acid, avoid the further corrosion of gastric acid to coat of the stomach and ulcer surface.

Summary of the invention

The present invention is a kind of compound recipe pantoprazole compositions of optimization, and it is to be active component with pantoprazole, sodium bicarbonate and magnesium hydroxide, exists in the ratio of 1: 37.5: 17.15 or 2: 37.5: 17.15.In the said composition, pantoprazole comprises its optical isomer and pharmaceutical salts thereof, and optical isomer comprises L-pantoprazole, dextral-pantoprazole and racemization pantoprazole, wherein preferred L-pantoprazole.Pharmaceutical salts comprises sodium salt, magnesium salt, preferred magnesium salt.Said composition can make up with suitable pharmaceutic adjuvant, makes oral formulations, comprises tablet, capsule, chewable tablet etc.

Said composition is in preparation preparation process, the unit consumption of pantoprazole is preferably 20mg or 40mg, preferred proportioning compositions is in the said composition: pantoprazole 20mg+ sodium bicarbonate 750mg+ magnesium hydroxide 343mg, pantoprazole 40mg+ Sodium bicarbonate 750mg+ magnesium hydroxide 343mg.Stronger by its proportioning mode capacity antacid of the provable compositions of the present invention of external antiacid experiment, and external zoopery shows that also the antiulcer effect of its compound recipe will obviously be better than the therapeutic effect of folk prescription pantoprazole or other proportioning.

The specific embodiment

Embodiment 1 compound recipe pantoprazole tablet

Prescription:

Preparation method:

1. pantoprazole, sodium bicarbonate, magnesium hydroxide, microcrystalline Cellulose are crossed 60 mesh sieves respectively, standby;

2. get pantoprazole, part magnesium hydroxide mix homogeneously, join in the mixed powder, the system soft material with 5% hyprolose aqueous solution, 24 mesh sieves are granulated, drying, 24 mesh sieve granulate, add the magnesium stearate of total amount 0.5%, 2.5% CMS-Na, adopt suitable punch die compressed tablets behind the mix homogeneously.

3. get sodium bicarbonate, microcrystalline Cellulose and residual hydrogen magnesium oxide, join in the mixed powder with 5% hyprolose aqueous solution, the system soft material, 24 mesh sieves are granulated, drying, 20 mesh sieve granulate add remaining magnesium stearate, CMS-Na, mix homogeneously.

4. with above-mentioned gained small pieces and mixed powder, adopt to be fit to punch die, be pressed into clad sheet.

If carry out coating for above-mentioned tablet, then obtain coated tablet, can be Film coated tablets etc.

Embodiment 2: compound recipe pantoprazole capsule

Prescription:

Preparation method:

With pantoprazole, sodium bicarbonate, and magnesium hydroxide, microcrystalline Cellulose PH102 all cross 60 mesh sieves, standby;

2. remove pantoprazole and part magnesium hydroxide mix homogeneously, add the magnesium stearate of the two total amount 0.5%, mix homogeneously is packed in the suitable capsule shells

3. get sodium bicarbonate, microcrystalline Cellulose and residual hydrogen magnesium oxide and progressively increase behind the method mix homogeneously, add remaining magnesium stearate according to equivalent, mix homogeneously, standby.

4. get above-mentioned gained Caplet, in the large capsule of packing into, one every, fill above-mentioned sodium bicarbonate mixed-powder then.

Promptly get compound recipe pantoprazole capsule.

Used capsule shells can be conventional capsule.

Embodiment 3: compound recipe pantoprazole chewable tablet

Prescription:

Preparation method:

1. pantoprazole, sodium bicarbonate, magnesium hydroxide, xylitol, mannitol, aspartame are crossed 60 mesh sieves respectively, standby;

2. get pantoprazole, part magnesium hydroxide mix homogeneously, join in the mixed powder, the system soft material with 2%PVP k30 alcoholic solution, 24 mesh sieves are granulated, drying, 24 mesh sieve granulate, the magnesium stearate that adds total amount 0.5% adopts suitable punch die compressed tablets behind the mix homogeneously.

3. get sodium bicarbonate, residual hydrogen magnesium oxide, xylitol and mannitol, mix homogeneously joins in the mixed powder with 2%PVP k30 alcoholic solution, the system soft material, 24 mesh sieves are granulated, drying, 20 mesh sieve granulate add remaining magnesium stearate and aspartame, mix homogeneously.

4. with above-mentioned gained small pieces and mixed powder, adopt to be fit to punch die, be pressed into clad sheet.

If carry out coating for above-mentioned tablet, then obtain coated tablet, can be Film coated tablets etc.

Embodiment 4: the mensuration of external acid-resistant strength.

Measuring the 150ml simulated gastric fluid (joins 2g sodium chloride and 7ml hydrochloric acid in the 10000ml water, pH1.2).Join in the digestion instrument, regulate mixing speed, make mixing speed be controlled at 100 rev/mins.Stir down and testing sample (compound recipe pantoprazole) is added wherein (is contrast with folk prescription pantoprazole sheet), stirring 2h.Above-mentioned suspension is transferred in the brown volumetric flask of 250ml, with remaining suspension in the pH10 ethanol liquid washing beaker, add the about 100ml of pH10 ethanol, the ultrasonic medicine dissolution that makes, continue to add pH10 ethanol liquid standardize solution to scale, filter with the organic filter membrane of 0.45um, pipette 4ml filtrate in the brown volumetric flask of 50ml, the water standardize solution is to scale.Measure this sample Chinese medicine concentration, calculate drug degradation percentage ratio (unit: %)

Embodiment 5: effect experiment

1. experiment modeling:

Fasting feedwater 24h before 60 rat modelings, etherization in the cover+beaker cotton balls nose appends anesthesia, iodine tincture, ethanol routine disinfection, the xiphoid-process lower abdomen hits exactly the 2～2.5cm that hits, and separates abdominal muscle, cuts off peritoneum, gently move to stomach outside the abdomen, at the stomach facies ventralis, body of stomach and pyloric antrum intersection thrust 0.4～0.5mm under the serous coat with microsyringe is flat, inject 10 glacial acetic acid 0.1mL, form pimple, stomach is sent back to, sew up abdominal muscle, skin.

2. experimental technique:

30 rats are divided into 3 groups at random: blank model group, pantoprazole group, compound recipe pantoprazole.Beginning administration in the 3rd day after the modeling, each group is all irritated stomach by 3mL/ (100g.d), blank model group is given the equal-volume normal saline, each organizes equal every day 1 time, totally 4 weeks. modeling 3d (before the administration), 17d (administration 14d), 31d (administration 28d) divides 3 batches to put to death rat, cut off the abdominal cavity along ventrimeson, take out stomach, cut off along greater gastric curvature, clean with the ice normal saline flushing. gastric mucosa is flattened on flat board, maximum major diameter and the wide footpath of vertical maximum with vernier caliper measurement ulcer. ulcer index (uI) is measured the major diameter and the wideest footpath of ulcer with slide gauge, multiplying each other calculates the ulcer area as ulcer index, ulcer area: S=1/4 * DL * DS * towering, and DL refers to the ulcer major diameter in the formula, DS refers to the ulcer minor axis, toweringly gets 3.14.

3. experimental result:

Each organize rat ulcer index (mm2) and ulcer inhibition rate comparison (x ± s, n=10)

Claims (5)

1. the present invention is a kind of new compound recipe pantoprazole compositions, it is characterized in that, it is to be active component with pantoprazole, sodium bicarbonate and magnesium hydroxide, exists in the ratio of 1: 37.5: 17.15 or 2: 37.5: 17.15.

2. the described compositions of claim 1 is characterized in that, pantoprazole comprises L-pantoprazole, dextral-pantoprazole and racemization pantoprazole.

3. the described compositions of claim 1-2 is characterized in that, pantoprazole comprises its pharmaceutical salts, particular certain cancers, magnesium salt.

4. the described compositions of claim 1 is characterized in that, can make up with suitable pharmaceutic adjuvant, makes oral formulations, comprises tablet, capsule, chewable tablet etc.

5. the described compositions of claim 4 is characterized in that, the unit consumption of pantoprazole is preferably 20mg or 40mg.