DE2226927A1 - COMPOSITION AND ADMINISTRATION FORM EFFECTIVE AGAINST ADDICTION AND CELLULITIS - Google Patents

Description

DRYING. BRIGITTE NETHE 23- (Pi) 2, 6 ₀ 1972

Patent attorney

8010 CBCRSBEWQ, Dept. Wllllramstr. 20th ! •! • tone 881O (area code Οβιοβ)

Society Anonymous dite "LABORATOIEE THEEAFOI", Paris (France)

Composition effective against obesity and cellulite and administration form thereof

The invention relates to compositions which are effective against obesity and cellulite and which are characterized by a content of L-thyroxine and 3,5,3 ^f -tri; iodothyroacetic acid together with a permeation-promoting factor such as hyaluronidase in a suitable carrier which is both a solvent for the active substances Components of the composition and in particular the 3,5,3'-triiodothyroacetic acid is also miscible with water and to which a suitable hardening or humidifying agent such as sodium dioctyl sulfosuccinate is added

In particular, diethylene glycol monoethyl ether is used as the carrier, which is known under the name "Transcutöl".

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The new compositions are particularly notable for the fact that the active ingredients in solution are very light to break through the skin barrier or to penetrate very easily through the skin and then directly in the area of the cellulite forming damaged cells come into effect,

Bs was further clinically found to be the common Administration of the two actual active ingredients in a synergistic manner Effectiveness increases, which are far more effective together than if they are used separately. The presence which provides hyaluronidase as a permeation-promoting factor for optimal penetration or diffusion of the active ingredients into the area of the from Cellulite afflicted body parts.

for the production of corresponding therapeutic agents are the 3 components, d _o h _o 3 »5,3'-Trijodthyroessigsäure, the thyroxine (especially in the form of alkali metal or sodium-L-thyroxine obtained by reaction with alkali metal especially sodium carbonate and preferably in approximately the same amount as the triiodothyroacetic acid) and the enzymatic diffusion-promoting factor (in particular the hyaluronidase) dissolves in a suitable solvent, which is preferably formed by the diethylene glycol monoethyl ether marketed under the name "Transcutol", to which a suitable wetting agent or Moisturizing agents are added, such as, for example, sodium dioctyl sulfosuccinate as surface-active agents sold by ABiERICAN OYANAMID CO under the name "Mannoxol".

The excipients bring an integral solubility of the Active ingredients without a corresponding chemical change in their composition "

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Two essential punctures come to this recipient in the recipe for:

1) The stamping agent (especially the diethylene glycol monoethyl ether) primarily ensures a complete dissolution of the active ingredients, which in this way is easy be taken along by the body shell (skin) acting as a barrier ο

2) The wetting agent or humectant (especially sodium dioctyl sulfosuccinate) allows penetration of the superficial fat layer of the epidermis, which is so for the local application of the product is prepared »

The various components of the particularly preferred compositions have the following properties »

The sodium L-thyroxine is an odorless and tasteless off-white powder, which is obtained by reaction of! -Thyroxin with sodium _o It is slightly soluble in water but quite soluble in alcohols was previously in an isolated state with an encouraging result for the Cellulite Treatment Uses »

3,5,3'-Irigodthyroacetic acid is insoluble in water, White powder soluble in alcohol previously used orally for the treatment of thyroid insufficiency was · The 3 »5,3'-tri; iodothyroacetic acid, which itself is not "Hydro-soluble" becomes thanks to the use of diethylene glycol monoethyl ether ("Transcutöl") brought into solution as a carrier in which it dissolves integrally «,

Hyaluronidase is an enzymatic permeation-promoting

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the paktor known, so that the indication is physico-chemical License plate unnecessary

The "Transcutol" or ₀ of diethylene glycol monoethyl ether is a transparent colorless liquid with a sweet odor that is miscible with water and alcohol and has the ability to penetrate the skin.

The> "Mannoxol" or "Sodium dioctyl sulfosuecinate" is a. Surface-active agent used in numerous pharmaceutical preparations in the form of creams, pomades, lotions, etc. finds. It is the most effective of the web humectants currently in use ο

The preparation of useful compositions according to the invention requires the application of a technique with which a milieu, i.e. an excipient, can be found, which on the one hand stabilizes the pH value of the "mannoxol" and, on the other hand, allows that its wetting or «. Humidification can have an effect *

For this reason, the required composition of the excipient must be found and the percentage of "mannoxol" to be used must be precisely determined. The wetting capacity of the "mannoxol" is determined according to the method already used by Draves-Clarkson. The solutions with 1 io mannoxol show a rapid drop in pH, which falls from 6.5 to 4 within a week, which explains that stabilization was consequently necessary »

The remarkable therapeutic properties of the composition according to the invention were based on pharmaceutical

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proven ecological examinations and clinical trials, which are reported on below:

I. Toxicological test

1) Acute toxicity

The acute toxicity test was carried out on mice with intraperitoneal administration of individual doses of the test substance The following results were achieved »

Sodium L-thyroxine »DI» _5Q (i. P,)> 3 g / kg triiodothyroacetic _{acid »DL 50} (i _o p.)> 275 mg / kg hyaluronidase: Dl ^ ie?»)> 3 g / kg

2) Harmlessness

The harmlessness test was carried out on gray-yellow Bourgogne rabbits of both sexes with an initial weight of about 2.3 kg for the males and 2.1 kg for the female (w) animals. 3 groups of 16 animals each (half male, half female) were treated as follows »

Group 1 (Ur ₀ 1 to 8, my nos. 9 to 16: w), non-treated comparative subjects

Group 2 (No. 17 to 24: m: No. 25 to 32: w): with 2 ml / kg treated animals

Group 3 (No. 33 to 40i m; No. 41 to 48 »w)» with 1 ml / kg treated animals,

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The treatment took place 5 days a week over a depilated area of about 5 x 5 cm in the neck area of the animals, to prevent oral ingestion of the applied product. The animals were also housed in individual cages to to prevent mutual licking. Food and fluids were given ad libitum. The attempt was over carried out for a month and the rabbits were killed at the end of the examination} an autopsy was performed with a view to this for an anatomic-pathological examination.

No damage whatsoever was found in the area of the outer body shell or skin and the adjacent connective tissue. The result of the hematological examination was normal. The weights of the organs examined showed individual variations in the liver, spleen, pituitary gland, adrenal glands, ovaries, thymus gland and testicles, but these varied from one group to the other showed no significant differences.

II. Pharmacological test

Analysis of the weight curves showed a significant decrease in weight in the treated animals while increasing the weight of the animals of the comparison group increased steadily and steadily (the animals were weighed twice a week).

III. Clinical trial

The clinical examination was carried out on more than 100 cases. In each case, a series of body measurements was taken at certain intervals above the floor on the upright test person made, in each case the scope of

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measured in the following places! Ankle, calf, squat, half thigh, thigh, bi-trochanter area, sinuous bone area, below the navel, at the navel, above the navel and Breast (at the nipple point) ο

At the same time, the weights were regularly noted. At the end of the 20 to 30 day treatment there was a marked decrease in initial body measurements in the "infiltrated ¹¹ zones" along with weight loss.

In each case, an improvement in the quality of the fabric, with complete disappearance of the local pain on pressure and an increase in subcutaneous Gewebstonus ¹ found "

Very interesting results have been found in men with obesity the waist and obesity in the area below the chin. -

Finally, good tolerability was observed in all cases

The treatment comprised the daily administration of an ampoule having the illustrative composition given below, which is merely an illustrative example of the possible uses of the therapeutic composition according to the invention should represent:

Sodium L-thyroxine 10 mg

3 »5,3'-tri; joethyroacetic acid 10 mg hyaluronidase 1000 I ₀ E.

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2 2 / £ 9? 7th

Percutaneous excipient:

»Transcutol« I q.s.po 1 ampoule of 10 ml "Mannoxol"

The contents of the ampoule were localized to those mentioned above applied to cellulitic areas of the body, with the absorption taking place subcutaneously »

From the point of view of therapeutic effectiveness " are the results obtained using this new drug very high and rate this therapeutic as the most advanced in this area of pathology a “This is one in relation to all the others at present practically applied means great progress. In the majority of the cases, the cellulitic disturbance or damage was great substantially or completely back, often even with a simultaneous astonishing remodeling of the local morphology.

The medicament is preferably in ampoules with a yellow, transparent content, which is intended for topical use the patients are suitable «. They gradually pour the contents of the ampoule onto the area to be treated and allow the liquid to penetrate the skin while slowly and evenly massaging with the fingers and the palm of the hand.

This form of administration is also of interest because, in the case of percutaneous administration, there is no toxicity whatsoever for the patient is to be feared and the active ingredients are retained in the cellulitic areas, which are only a small proportion release the active ingredients into the general circulation,

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Claims (3)

- 9 claims (Ij Composition effective against obesity and cellulite, characterized by a content of L-thyroxine and 3.5i3'-tri; iodothyroacetic acid together with one permeation-promoting factor such as hyaluronidase in solution in a suitable carrier which is both solvent for the active ingredients of the composition and in particular the 5,5,3'-triiodothyroacetic acid as well as miscible with water is and a suitable wetting or humidifying agent such as Sodium dioctyl sulfosuecinate is added » 2. Composition according to claim 1, characterized in that the carrier is formed by diethylene glycol monoethyl ether will. 3. Composition according to claim 1, characterized by the following composition (per administration unit): Sodium L-thyroxine 10 mg 3,5,3'-triiodothyroacetic acid 10 mg hyaluronidase 1000 IU ₀ Percutaneous excipient: - Diethylene glycol monoethyl ether / _n _ _ _in _, -, ^f C [# CJ · P ο Iv UiX - wetting agents 4o form of administration of the composition according to one of the preceding claims and in particular according to claim 3 in the form of ampoules for local application by percutaneous absorption with manual massage. 209883/1153