LU85552A1 - MEDICINAL COMPOSITION FOR THE TREATMENT OF PERIARTHRITES AND SIMILAR CONDITIONS - Google Patents

Description

- 1 - X-RAY HOLDING S.A.

2, Boulevard Royal - Luxembourg

MEDICINAL COMPOSITION FOR THE TREATMENT OF PERIARTHRITES AND SIMILAR CONDITIONS

I The subject of the present invention is a medicinal composition for the treatment of periarthritis and similar ailments by iontophoretic treatments or by therapeutically equivalent treatments.

It is well known that periarthritis and similar conditions, such as abarticular rheumatism in general, dismetabolic rheumatism and rheumatoid arthritis, are often accompanied by the formation of calcium salt deposits in correspondence with the ligaments of the affected joints. , and that the presence of these deposits, constituting an inflammatory agent, often neutralizes, or at least reduces, the effect of systemic or topical treatments carried out by anti-inflammatory drugs, and then it can cause relapses in cases where these treatments had a temporarily positive effect. On the other hand, it is estimated that, if these 15 calcareous deposits could be eliminated, many periarthritis and similar ailments could be easily overcome by anti-inflammatory drugs, and some of them would even downgrade spontaneously.

»Ο» 4.

I The treatment of periarthritis and similar ailments is starting now, alongside pharmacological anti-inflammatory treatments, especially on physical treatments (gymnastics, manipulations, massages, pull-ups, infrared electromagnetic radiation, lumi-5 nous, ultra-violet or röntgen , electromagnetic inductions, application of ultrasound and so on), which essentially have the effect of locally activating the circulation of the blood in order, moreover, insufficiently achieved, to dissolve the calcareous deposits.

However, there has hitherto been no drug available 10 which makes it possible to act directly with efficiency in the sense of destroying or reducing these calcareous deposits. Certainly, there are known drugs for systemic use which are capable of reducing calcemia and therefore, in theory, of giving rise to a tendency to dissolve calcareous deposits, but, particularly with a view to the limited solubility of these deposits , their effect in this context would be extremely slow, and it would only be verified by doses such as to produce a high systemic hypocal cemia, which cannot be tolerated for a long time in the whole organism. On the other hand, these drugs are not suitable for topical use, because they are not absorbed in sufficient quantity and, above all, they cannot reach localizations, which are not superficial and sometimes in effective concentrations. fairly deep, calcareous deposits that should be attacked.

The object of the present invention is to produce a medicinal composition having a hypocalcemic and anti-inflammatory effect, which can be introduced into the organism so as to reach in effective concentrations the places where the calcareous deposits to be attacked are present, without modifying in an important way the systemic calcemia of the organism, so that it becomes possible to reduce and, if necessary, entirely destroy the calcareous deposits which have arisen in correlation with periarthritis or with a similar affection, in at the same time achieving an adequate local anti-inflammatory effect. To achieve this object, the invention proposes to use, for the introduction of the drug, iontophoretic treatments which, carried out in a timely manner, make it possible to transport to pre-established places at inside the body effective amounts of active substances, without these systemically spreading in the body in high concentrations; or to treatments equivalent to iontophoretic treatments from a therapeutic point of view.

The achievement of the sought-after medicinal composition therefore required, on the one hand, to recognize, among the substances having a hypocalcemic effect, a specific agent adapted to be used in an ionophoretic technique or equivalent from the therapeutic point of view, and d on the other hand, to combine this agent with a vehicle capable of promoting the transport of said agent, as well as, preferably, of exerting an anti-inflammatory action at the same time.

By research conducted by the author of the present invention, it has emerged that suitable hypocalcemic agents for the prefixed purpose are the salts of edetic acid. Among these salts we must first name the disodium salt of edetic acid, also known as disodium te-tracemate, the chemical formula of which is developed as follows 20 Na 0 0 C H2 C C H2 C 0 0 Na s /

N H2 C - C H2 N

H00CH2C / CH2C00H

This substance has a strong hypocalcemic effect and is now used by intravenous injection to reduce the systemic level of calcium in the blood in the event of ipercalcemia, especially in children and infants, as well as to prevent disadvantages during massive blood transfusions. This substance can be ionized giving rise to an edetic acid anion and two sodium cations, so that, subjected to an electric field, it achieves a migration of edetic acid (which is the effective component from the point of view .therapeutic) to the anode.

In the experiments carried out for the development of the present invention, the disodium salt of edetic acid was used specifically, which is marketed under the name of "disodium tetracemate". Another similar product, which may be used according to the invention is calcium sodium sodium, commercially available under the name "disodium calcitetracaceous mate".

For effective use in iontophoretic or therapeutically equivalent treatment, the salt of edetic acid should be introduced into a suitable vehicle, preferably having anti-inflammatory activity. Through the research of the author of the invention, it has emerged that, for this purpose, aqueous solutions or suspensions of enzymatic proteins, preferably class 3 enzymes (hydrolases) and even more preferably, are suitable as active vehicles. those of subclass 3.2. In a particular way, mucopolysaccharidase and alphachymotrypsin have been shown to be suitable for this purpose.

The experiments were carried out in particular by using the product sold under the name of "lyophilized Alphachymotrypsin Choay" and the testicular mucopolysaccharidase constituting the lyophilized fraction of the product sold under the name of "Thiomucase" favorable and finding that the latter is the most preferable.

A composition which is now preferred, and which has been shown to be particularly suitable for the iontophoretic treatment of perriar-thrites and similar ailments, comprises a solution in water of 2.5 ml of the disodium salt of the acid. edetic with 5¾ (è ampoule of "T-tracëmate disodium") and 100 TRU of testicular mucopolysaccharidase (the ampoule of the lyophilized component of "Thiomucase").

For carrying out the treatment, an apparatus for io-30 nophoresis was used, provided with a potentiometric adjustment means, by which a low current was maintained, with an intensity between I and 3 mA (preferably for the value 2 mA) for a period of 15 to 30 min (with »a - 5 - I preferably for values between 20 and 25 min), applying the negative polarity to the buffer containing the active substance. These iontophoretic treatments must be repeated a number of times varying from one case to another, in general from 15 to 30 times, at a distance of 2 to 10 5 days, preferably with a frequency of 2 to 3 times a week. .

For this treatment, the negative electrode must be well placed opposite the calcification, observed and usually located by radiographic control, while the positive electrode must be placed in a suitable position facing the negative.

10 After a number of sessions, which varies according to the patient's sensitivity (sometimes already from the first session), small pinhead burns appear on the skin, at the place of treatment. should be treated with normal regenerative creams applied after each session.

A number of cases have been treated with this therapeutic scheme and with the preferred composition indicated above, obtaining the summary results in the appended table. In this report, for 9 patients who represent normal cases, the sex of the subject was reported; the approximate period of time that you have been suffering before starting treatment with this composition; the date on which the presence of calcifications was first observed by radiographic means; the dates of the radiographic checks carried out at the beginning and respectively at the conclusion of the treatment with the present composition, to ascertain the extent of the calcifications before and after the treatment; an approximate classification of the extent of the calcifications observed at the start of the treatment; the results of the treatment, in the form of an estimate of the percentage reduction brought to the pain felt by the patient and, respectively, to the calcifications observed by radiographic route; and the number of 30 sessions to which the patient was subjected to obtain the indicated results. It is noted that, in cases No. 6 and No. 9, in view of the extreme importance of calcifications at the beginning of the treatment, "- 6 - I this was extended by additional sessions in addition to the number of 20 taken as a normal base, finally arriving at the desired results.

As emerges by examining these results, the ionophoreptic treatment of peri arthritis and similar ailments by the composition according to the invention makes it possible to obtain, in a reasonably short time, a significant reduction in either the pain that calcifications associated with the affection, by a treatment which, thanks to its local character, does not modify the systemic conditions of the organism, and therefore can be adopted without danger even in the cases of particularly sensitive or suffering patients of intolerance.

In the foregoing, specific reference has been made to the use of the medicinal composition according to the invention in a method of therapeutic treatment based on iontophoretic treatments, but it should be understood that this composition can be used in treatment of any other kind, substantially equivalent to iontophoretic treatments from a therapeutic point of view, such as, for example, mesotherapy.

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Claims (4)

2. Medicinal composition according to claim I, characterized in that said salt of edetic acid is a disodium salt. 3. Medicinal composition according to claim I, characterized in that said enzyme proteins are class 3 enzymes (hydrolases). - 4. Medicinal composition according to Claim 3, characterized = in that the said enzymatic proteins are enzymes of subclass 3.2. 15 5. Medicinal composition according to Claim 4, characterized in that the said enzymatic proteins comprise mucopolysac-charidase. 6. Medicinal composition according to claim 4, characterized in that said enzyme proteins comprise alpha-chymotrypsin. 7. Medicinal composition according to claim 5, characterized in that it contains, in aqueous solution, 2.5 ml of the disodium salt of edetic acid at 5¾ and 100 TRU of testicular mucopolysaccharidase. Drawings: ......... plates 5 —s2 — pages of which ........ A cover page ........ jfc ..... description pages ... .... J ....... claim pages ....... descriptive abstract Luxembourg, 2 4 SEP. | 984 The agent ^ /) / Ç