JPS62207209A - Gradually releasing oral preparation - Google Patents

Abstract

PURPOSE:A gradually releasing oral preparation that is composed of soybean protein, a foaming agent and drugs, thus suspending in the stomach, after being given, to release the drugs gradually and feed the drugs in high concentration enough to manifest the remedial effect. CONSTITUTION:The objective gradually releasing oral preparation is composed of (a) soybean protein, preferably a separated protein of more than 90% content or concentrated protein of more than 70% content in the form of powder or granules, (b) a foaming agent, e.g., a carbonate or bicarbonate or a mixture thereof with an organic acid and (c) drugs, preferably is in the form of tablets, granules, or capsules. the preparation stays in the stomach as a suspension, swells by absorbing gastric juice to release the drugs so that the concentration of the drugs are kept high for hours at the affected sites or drug-absorbing sites. The weight ratio of (a) to (b) is preferably 1:(0.4-4).

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to oral sustained release preparations. More specifically, after oral administration, an oral sustained-release preparation is characterized in that it floats in the stomach and gradually releases the drug, supplying the drug at a concentration sufficient to obtain a therapeutic effect over an extended period of time. Regarding.

BACKGROUND ART Conventionally, formulations and formulation methods for delaying the release of a drug from a formulation and maintaining the efficacy of the drug for a long time include:
Proposals for each scale are made. Among these, the following examples are examples of attempts to maintain an effective blood concentration by releasing the drug over a long period of time while the drug remains in the stomach.

Ill et al., published in Japanese Patent Application Laid-Open No. 49-61323, attempted to coat a core made of a drug with a polymer film that swells in gastric fluid, and use its mechanical size to prevent passage through the pylorus and extend the residence time in the stomach. JP-A No. 51-41591 describes a method in which a fatty substance with a light specific gravity is suspended in gastric juice, and the drug is released through the formed hydrogel membrane. is listed.

JP-A No. 50-121418 discloses that hollow materials such as expanded polystyrene, hard gelatin capsules, and expanded grains are coated with a gastric fluid-resistant coating, and then a drug is coated to float and remain in the gastric fluid. It describes how to do this.

JP-A-52-76418 discloses that gastric fluid can be treated by coating a foaming agent mainly consisting of bicarbonate with a coating agent containing a drug, or by coating a mixture of a foaming agent and a drug with a conventional coating agent. A method has been described in which the drug is gradually released by suspending the drug in it. All of these methods have drawbacks, such as the sustained drug release effect being less than 4 minutes.

C. Purpose of the Invention The present inventors, unlike these conventional techniques, have developed a method for treating gastric local diseases and systemic diseases for which sustained release is expected to increase the effect by keeping the drug suspended in the stomach and by reducing the amount of drug release from the drug. As a result of intense research into drug formulations aimed at treating drugs by sustained release, we found that, surprisingly, when a preparation consisting of soy protein, a foaming agent, and a drug was orally administered, it remained suspended in the back, causing the drug to gradually release. The inventors have discovered that such a preparation is extremely excellent as an oral sustained-release preparation, and have arrived at the present invention.

The present invention is an oral sustained release formulation consisting of soybean protein, an effervescent agent, and a drug.

The soybean protein used in the present invention is a concentrated protein with a protein content of 70% or more, and a protein content of 9% or more.
Soybean protein with 0% or more isolated protein and in powdered or granular form is preferred.

As the blowing agent used in the present invention, carbonates or bicarbonates such as sodium hydrogen carbonate, sodium carbonate, potassium carbonate, and potassium hydrogen carbonate are used.

Alternatively, a mixture of these salts and an organic acid such as citric acid, tartaric acid, succinic acid, fumaric acid, maleic acid, or ascorbic acid may be used. To further increase effervescence or to target patients with achlorhydria, carbonate or bicarbonate wI salts may be combined with citric acid, tartaric acid, succinic acid, fumaric acid, maleic acid, or ascorbic acid. It is better to use B [in combination.

The ratio of effervescent agent to soybean protein contained in the formulation is determined by the strength and floatability of the tablet, for example, in the case of tablets, but is usually 0.1 to 4 effervescent agents per ton of soybean protein. It is preferable to use a blowing agent of 0.2 to 11 parts by weight per part by weight of soybean protein. It is generally preferable to use part i.

The active ingredient included in the present invention may be any drug for treating intracavity diseases or systemic diseases for which the therapeutic effect is expected to be further increased than in the past through sustained release. Examples include:

a, Gastrointestinal drugs allantoin, aldioxane, alcloxane, pirenzebin hydrochloride, secretin, urogastrone, cetraxate, cimetidine, ranitidine, p-(trans-4-aminomethylcyclohexylcarbonyl)phenylpropionate hydrochloride, prostaglan Peptic ulcer treatment agents such as gins: synthetic aluminum silicate, natural aluminum silicate, magnesium bismuth aluminate silicate, dried aluminum hydroxide gel.

hydrotalcitate, magnesium aluminate metasilicate,
Antacids such as magnesium silicate, magnesium oxide, heavy magnesium oxide, magnesium hydroxide, magnesium carbonate, precipitated calcium carbonate; sucrose sulfate, hebuscutin.

Anti-pepsin drugs such as streptostatin; anti-inflammatory enzymes such as pepsin, diastase, and lipase.

b. Central nervous system drugs Hypnosedatives such as diapipam and estazolam.

Anticonvulsants such as phenytoin, meprobamate, and nitrazepam; acetaminophen, ethenzamide, salibulamide, and pentazocine.

Clofezone, Indomethacin, Ketoprofen, Naproxen, Flubibrofen, Diclofenac, Clidanac, Alclofenac.

flufenamic acid, mefenamic acid, sulindac.

Antipyretic, analgesic and anti-inflammatory drugs such as corticosteroids including piroxicam, menthol, camphu 7+, D-penicillamine, dexamethacin, triamcinolone, betamethacin, and prednisolone; Neuropsychiatric drugs such as nichlorbromazine; isoprenaline, petahistine mesylate, scopolamine, etc. anti-vertigo agents; general anesthetics, etc.

C. Allergy medicines or antihistamines, diphenhydramine, beriactin, etc.

d. Cardiotropic agents such as digitalis and ubidecarenone; β-blockers or antiarrhythmia agents such as vindolol, propranolol hydrochloride, alprenolol hydrochloride, oxprenolol hydrochloride;
subironolacone, mebcrothiazide, metolazone,
diuretics such as tribamide, furosemide, benflucit;
Rehirubin, clonidine hydrochloride, methyldopa.

hydralazine, syrosingobine, recinamine.

Antihypertensive agents such as dihydropyridine derivatives including cinnarizine, prazosin hydrochloride, and nifedipine Vascular reinforcement agents such as niltin and carbazochrome; Vasoconstrictors such as dihydroergotamine mesylate and dihydroergotoxine mesylate dinitroglycerin, isosorbitol nitrate, dirazep hydrochloride, and nifedipine , diltiazem hydrochloride, trimetazidine hydrochloride, trapidil, diviridamol, and other coronary vasodilators; inositol, bekinicodine, and other peripheral vasodilators; arteriosclerotic agents, such as clofibrate;
Pentoxifylline, cytochrome C, degistran sodium sulfate, pyrithioxine, citicoline, nicardipine hydrochloride, dopamine hydrochloride, prostaglandins, prostacyclins, doptamine hydrochloride.

alprostadil, ifenbrodil tartrate, etc.

e. Respiratory agents Antitussive and expectorant agents such as ephedrine, codine, bromhexine: isobroterenol, dextromethorphan, orciprenaline, ibratrobium bromide, cromoglycic acid, etc.

f. Hormone or anti-hormonal agents human growth hormone, flutecothrobin. oxytocin,
Pituitary hormones such as vasobrecin and brothyrelin tartrate; male hormones such as testosterone; progesterone. Female hormones such as estradiol, bisalivary gland hormones, thyroid/parathyroid hormones, anabolic steroids, adrenal hormones, etc.

0. Urogenital organ drugs Uterotonic drugs such as Ziprost and Dinoprostone.

70 Metabolic medicines Alphacalcidol Cicolecalciferol, Mecobalamin and other vitamins: Nourishing and tonic altering agents: Glutathione.

ΔT P , abrotilin, gabexate mesylate, etc.

i. tumor drugs Krestin, ancitabine, mitomycin.

methotrexate, carbocone, cytarabine.

5-fluorouracil derivatives including bisibanil, tegafur and carmofur. 5-fluoro-2'-deoxyuridine and its derivatives, etc.

j. Antibiotics such as deracycline antibiotics, penicillin antibiotics, and cephalosporin antibiotics.

k. Chemotherapy agents such as clotrimazole, virolnidoline, arabosufu-7rin, sulfa drugs, etc.

The age of such drugs is appropriately determined depending on the strength of the activity of each drug.

The oral sustained release preparation of the present invention is preferably in the form of tablets, granules, fine granules, or capsules filled with tablets, granules, or fine granules.

The oral sustained release preparation provided by the present invention with excellent gastric retention is produced as follows by a method known per se.

That is, soybean protein, effervescent powder, and drug are uniformly mixed, a lubricant and an excipient are added as necessary, and tablets are formed by direct compression, or dry granules are formed by a conventional method.

Granules or small tablets may be filled into hard capsules if desired.

The soybean protein, foaming agent, and drug may be mixed together to form fine granules as is, or two tablets of granules or the like may be crushed to form fine granules.

E. Effects of the Invention The effects and characteristics of the formulation provided by the present invention described above include the following points.

1. It stays suspended in the stomach for a long time, so the drug can act directly and locally at high concentrations in the stomach, and the drug itself passes through the absorption or action site without releasing the drug. There is no need to put it away.

2. Swelling occurs gradually by absorption of gastric juice, and the drug is released from the swollen part, so it can be ingested for a long time and the drug can be continuously supplied to the diseased or absorption site.

3. The manufacturing method is easy, and the molding is done by pressure molding J3 and dry grinding, so the stability of the drug is not compromised, and it is also advantageous from an economical point of view.

Example Example-1 Soy protein isolate (protein content of 90% or more).

Product name Fujipro R) 20g, sodium hydrogen carbonate 70g
and 5 g of cinnarizine were evenly mixed and directly compressed into tablets with a tableting pressure of 700 and 9/cd to form tablets with a diameter of 13#III and a thickness of 2.
tm.

Tablets weighing 350 Rg were produced. This tablet contains 50 IPg of cinnarizine in one tablet.

Example 2 Using the tablets prepared in Example 1, an in VitrO dissolution test was conducted three times to confirm floating properties and sustained release properties.

(Conditions) Equipment N: Diurnal X dissolution test equipment Method: 2nd method (paddle droplet) Test solution: 1st solution 800d! Temperature: 37° C. Rotation speed: 700 rE) 1 This tablet remained floating on the surface of the test liquid even after 4 hours.

Example 3 The tablets prepared in Example 1 were orally administered to four pegle dogs, and by measuring the blood concentration, it was confirmed that the drug was being released in a sustained manner.

(Margin below)

Claims (1)

[Claims] 1. An oral sustained release preparation comprising soy protein, a foaming agent, and a drug. 2. The oral sustained-release preparation according to claim 1, wherein the soy protein is a powdered or granular concentrated protein with a protein content of 70% or more or an isolated protein with a protein content of 90% or more purified from soybeans. . 3. The oral sustained release preparation according to claim 1 or 2, wherein the effervescent agent is a carbonate, a bicarbonate, or a mixture of a carbonate or bicarbonate and an organic acid. 4. The oral sustained release preparation according to any one of claims 1 to 3, which is in the form of a tablet, granule, fine granule, or capsule. 5. Foaming agent is 0.1 to 4 parts by weight of soybean protein
The oral sustained release preparation according to any one of claims 1 to 4, which is in parts by weight.