DD250465A1 - METHOD FOR PRODUCING A NEW MEDICAMENT - Google Patents

Abstract

Process for the preparation of a new medicament for the treatment of periodontitis, gingivitis, tooth loosening due to stress, endodontic pathology and surgical stomatology. The object of the invention is to propose a new method for medicaments, wherein this contains an already pharmaceutically characterized, pharmacologically-toxicologically tested and clinically proven active ingredient with a different indication. The object of the invention is achieved by mixing this active substance, p-aminomethylbenzoic acid (PAMBA), with solid or liquid tracer substances and then bringing it into the desired pharmaceutical form. The active ingredient is administered orally in humans from 30 mg to 6 g, parenterally from 15 mg to 3 g, preferably in 3 to 4 individual doses, or locally, with suitable formulation and variation of concentration (generally 5 mg to 1 g).

Description

For this 4 pages drawings

Field of application of the invention

The invention relates to a process for the preparation of a new medicament for the treatment of peridontitis, gingivitis, tooth loosening as a result of bad loading, and the use in the context of endodontics and surgical stomatology.

Characteristic of the known technical solutions

Among the most widespread substances with the clinical indication as antifibrinolytic agents include:

p-Aminomethylbenzoic acid -PAMBA

E-aminocaproic acid -EACA

Diaminomethylzyklohexancarbonsäure-AMCA

The preparation of the drug is z. As a tablet, as follows, in addition to the active ingredient filling, lubricating, binding and disintegrating agents are used. Such means are:

- Strength

- Dextran

- Sodium carboxymethylamylpectin

- Aluminum silicate

- fatty alcohols

- Sodium alkyl sulfates

- gelatin

PAMBA tablets are made according to the following instructions: 500g PAMBA 100g tablet granules,

consisting of 70% potato starch 30% lactose glycerine gelatin solution 50g talc

650g = 2000 tablets

The deficiencies of these known methods are that the released from the preparations or ready-made preparations in the organism active ingredient PAMBA (and other drugs from the Pharmakonklasse of antifibrinolytics) as a therapeutic, oral, parenteral or local application, only in those known from the literature Indikationssteilungen,

z. B. can be used as an antifibrinolytic, but not at o. G. Indications in the context of the dental specialty.

Aim of the invention

The object of the invention is to develop a process for the preparation of a medicament which opens up new indications for the field of stomatology.

Explanation of the essence of the invention

The invention has for its object to develop a method for producing such a drug. It has surprisingly been found that PAMBA is particularly advantageous for the preparation of medicaments:

- gingivitis (plaque-induced gingivitis, acute gingivitis, acute necrotizing ulcerative gingivitis, traumatogenic gingivitis, hormone-related gingivitis and subsequent pathological-anatomical changes of the periodontium and its surroundings in acute, subacute, subchronic and chronic forms);

Against periodontitis (juvenile periodontitis, progressive acute periodontitis, periodontal abscess, periodontitis with particular gingival changes, acute periodontitis, acute necrotizing ulcerative periodontitis, traumatogenic periodontitis, hormone-related periodontitis, dösquamative periodontitis and subsequent pathological-anatomical changes of the periodontium and its surroundings in acute , subacute, subchronic and chronic forms);

- against atrophy of the periodontium (gingivitis, periodontal atrophy and subsequent pathological-anatomical changes of the periodontium and its surroundings in acute, subacute, subchronic and chronic forms);

- against gingival hyperplasia (gingivafibromatosis and subsequent pathological-anatomical changes of the periodontium and its surroundings in acute, subacute, subchronic and chronic forms);

- against tooth loosening as a result of traumatic occlusion, as a result of congenital and acquired malocclusions, during and after orthodontic or orthodontic treatment and as a result of age-related, chronic-destructive processes;

In pathologic-anatomical changes of the pulp, the periodontal area and its surroundings in acute, subacute, subchronic and chronic form, in endodontics in pathological processes in the form of pulpitis acuta coronalis, pulpitis acuta radicularis, pulpitis chronica clausa, Pulpitis chronica aperta granulomatosa and pulpitis chronica aperta ulcerosa may occur;

In the case of pathological-anatomical changes of the periodontium and its surroundings in acute, subacute, subchronic and chronic forms which are unspecific soft-tissue disorders in the context of surgical stomatology (diseases which are clinically represented as edema, infiltrate, abscess and phlegmon, Odontogenic subperiosteal and submucosal infections, odontogenic cysts, Dolor post extraction, Dentitio difficilis, etc. Infections in the area of a retained tooth, osteomyelitis and iatrogenic injuries). - ^

As the method according to the invention of such a drug, all known methods are suitable, which have the preparation of the usual oral and parenteraleri application forms such as tablets, powders, dragees, capsules, suppositories and ampoules as well as packaging for local application to the content. In this case, the active ingredient is mixed with solid or liquid carriers and then brought into the desired dosage form.

The active substance is administered orally or rectally in daily doses of 30 mg to 6 g in humans, which are preferably administered in 3 to 4 individual doses.

For parenteral administration, an amount of 15 mg to 3 g is generally sufficient.

For topical administration, 5 mg to 1 g of active ingredient are generally used.

The advantages of the process according to the invention compared with the prior art are to be proven with some experimental results 7 ~~~~ about the effect of the medicament thus produced.

1. Clinical efficacy

The clinical efficacy of PAMBA with respect to the indicated indications was tested by known methods and compared with the effect of known drugs.

2. Efficacy in animal experiments

Some experimental results regarding the comparison of the effects of PAMBA and D-penicillamine, the latter being used therapeutically in addition to its use as a chelating agent in heavy metal intoxications also in rheumatoid arthritis, are shown in FIGS. 1 to 4.

On a typical experimental animal model, relevant to o. G. Pathological processes in humans, it has been shown that when applied to the drug produced with the active ingredient PAMBA the hydroxyproline and collagen content in the tissue removed is significantly reduced at heavy load on the periodontium and its surroundings. In contrast, D-penicillamine was ineffective. The particular advantage of the inventive method is that when using the drug on humans at o. G. Indications of the pathological-physiological Circulus vitiosus, triggered by the primary diseases mentioned and subsequently accompanied by a proliferation of collagen tissue, which in turn amplifies the corresponding degenerative changes, is interrupted.

From PAMBA, a 1% aqueous, cold solution or a 4% aqueous, warm solution could be prepared. In addition, the substance is readily soluble in alcohol, dimethylsulfoxide and dimethylformamide.

embodiment

1. 300g PAMBA mixed with 35g potato starch and 15g lactose and then granulated with glycerine, gelatin solution and 25g talc. From the granules 1 000 tablets are pressed. The tablets are then available for oral administration.

2. 60mg PAMBA are placed in physiological saline and then neutralized with NaOH to give the sodium salt of p-aminomethylbenzoic acid and are available in ampule form (2 ml).

3. 300mg PAMBA are placed in physiological saline and neutralized with NaOH to give the sodium salt of p-aminomethylbenzoic acid. The solutions thus prepared and other concentration series are packaged in 10 ml screw cap bottles and are for local application, e.g. Brushing u.a. the gingiva, available.

4. Gelatin films containing 1% of the sodium salt of p-aminomethylbenzoic acid and gelatin films with higher or lower contents of the sodium salt of p-aminomethylbenzoic acid are available for local application, u. a. on the 'gingiva, available.

5. Other assemblies for local application, u. a. on the gingiva, with variation of the content of sodium p-Aminomethylbenzoat were developed analogously.

legends

Influence of p-aminomethylbenzoic acid (PAMBA) on the hydroxyproline content of the gingiva and the periodontium of male Wistar rats in the stress test.

Strain of the periodontium by a tension spring wire between the gnaw and the first molar over a period of 4 weeks. Twice daily local administration of PAMBA (20 mg / kg body weight) into the vestibule at the level of the first molar.

Control animals (K) were administered 0.9% NaCl solution under the same experimental conditions. Injection volume 0.2 ml / 100g body weight. Tissue samples were taken from the periodontium after 4 weeks. Weights of the Vesuch and control animals did not differ significantly during the experimental period. Conditions of keeping the animals:

12h. Light-dark rhythm, water and food ad libidum.

Plot of the mean value (x) and the standard error of the mean value (S _x ) η = number of test animals. Calculation of the sig- nificance thresholds for students. Probability of error: ρ <0.025 - *; ρ <0.001 - κχ.

Fig. 2

Influence of p-aminomethylbenzoic acid (PAMBA) on the collagen content of the gingiva and the periodontium of male Wistar rats in the stress test.

Experimental procedure s. Legend of Fig. 1 Plot of χ and S _x , ρ <0.025 - χ; ρ <0.001 - xx.

Influence of D-penicillamine (DPC) on the hydroxyproline content of the gingiva and the periodontium of male Wistar rats in the stress test.

Daily single oral administration of DPC (166mg / kg body weight) in 1% othoxoelesurvog (0.5ml / 100g body weight) over a 4 week period. Control animals received 0.5ml / 100g body weight of ethoxose.

Experimental procedure s. Legend of Fig. 1. Plot of χ and S _x . Differences between experimental and control animals not significant.

Influence of D-penicillamine (DPC) after oral administration on the collagen content of the gingiva and the periodontium of male Wistar rats in the stress test.

Experimental procedure s. Legend of Fig. 1. Plot of χ and S _x . Differences between experimental and control animals not significant.

Claims (2)

1. A process for the preparation of a novel medicament for the treatment of periodontitis, gingivitis, tooth loosening due to bad loading, the pathological events in the context of endodontics and surgical stomatology, characterized in that antifibrinolytic agents, in particular p-aminomethylbenzoic acid (PAMBA) and E-aminocaproic acid (EACA) mixed with solid, liquid or gaseous carriers or other known active ingredients and then brought in all the usual forms of application, such as tablets, powders, dragees, capsules, suppositories and ampoules and in suitable formulated for local application. 2. The method according to item!, Characterized in that dosage forms, such as tablets, powders, capsules or suppositories, from 30 mg to 6 g of active ingredient, ampoules of 15 mg to 3 g of active ingredient and confectioning with variation of the active ingredient content for topical application within the indication of the field of stomatology.