KR20020063841A - Colloidal composition for esthetic correction - Google Patents

Abstract

The present invention relates to methods used for the purpose of correcting dermatological disorders and to chemical compositions of carboxyglyconate hydrolactic of magnesium. In particular, the present invention relates to the removal of wrinkles, non-phrases, reduction of the lip and correction of contours, keratosis, enhancement of the cheek area, reduction of the lobe of the hips, the inclination of the buttocks area, human aging or external factors such as It relates to a composition that is applied to correct dermatological defects such as senile spots and changes in the skin through the action of).

Description

Colloidal composition for esthetic correction

Human skin, when intact, is a barrier to many natural and synthetic materials. Although cosmetic and pharmaceutical formulations may be pharmacologically effective through oral administration or other systemic administration of these formulations, many of the currently known formulations are little or no effective for topical application to the skin.

The topical utility of a pharmaceutical formulation depends on two main factors: (a) bioavailability of the active ingredient in the topical formulation and (b) absorption, penetration and distribution of the active ingredient in the area of skin to be treated.

The formation of wrinkles may be due to damage caused by natural aging and / or sunlight. Fine wrinkles on the face are most often caused by natural or congenital aging, while deep wrinkles on the face are the result of skin with acne or sunlight. Despite the actual mechanism of wrinkle formation remaining unknown, the formation of fine visible wrinkles is allowed due to a decrease in the number and diameter of elastic fibers in the papillary dermis as well as a decrease in the dermis atrophy and adipose tissue.

Histopathological and electron microscopic studies indicate that thick wrinkles are caused by excessive deposition of abnormal elastic material and thickening of the skin in the upper dermis.

Despite the fact that skin defects do not have physiological significance, these defects can cause serious physiological problems in people with them. In many societies, the owners of these defects are different from indicating signs of aging, and wrinkles have been a race's greatest concern since far past.

Grafts and grafts that are currently usefully used for correcting bedrock and body defects present difficulties with long-term consequences in handling, complications, and deficiencies.

In the description of the art it is known to use various vehicles for the purpose of correcting aesthetic defects. One of these vehicles is bovine collagen, which is a long chain protein that is at high risk for allergies and is a virus such as cerebellar encephalitis, or persistent future complications such as inflammatory processes, strong allergic phenomena and mainly autoimmune diseases (eg, Rheumatoid arthritis).

Another vehicle, also known in the art, is liquid silicone, but liquid silicone produces silicon tumors and has not been fully approved by the inventor for medical use.

Aesthetic surgery may be mentioned during traditional treatment to remove wrinkles, which, while removing wrinkles, presents many disadvantages, including scarring on the skin by these operations, which are considered to be very difficult to hide frequently. do.

Another method of removing wrinkles involves the use of grafts made from various materials. For example, Brazilian patent application PI 9503052-2, filed on June 22, 1995, by Miguel Marques Oliveira Jr., is incorporated herein by reference. PI 9503052-2 describes xenograft surgical implants for aesthetic modeling and / or increase in aesthetic definition of the forehead. Prostheses made in accordance with PI No.9503052-2 are made of semi-rigid solid silicone and implanted in the front region to correct defects, but the disadvantages of this implant are many, including rejection, allergic reactions, and limited effectiveness Limited to areas.

Brazilian Patent PI 8907235-9, issued to Dr. Martin Lemperle on September 24, 1996, relates to a composition for use in aesthetic medicine, which is incorporated herein by reference. PI 8907235-9 describes compositions for filling defects at the skin level. This composition uses polymethylmethacrylate microspheres in a suspension medium. Suspension media consist of water, alcohols or mixtures thereof, and tension-active substances such as Tween 80. However, this composition is not stable, so it is necessary to maintain it under stringent storage conditions and under constant refrigeration.

It has now been found that dermatological defects can be corrected without exhibiting relevant disadvantages in the mention of the art.

Summary of the invention

The present invention relates in particular to methods and chemical compositions which are used for the purpose of correcting dermatological disorders, but which can be used for other purposes in repair surgery.

One object of the present invention is to contain a complete blend of substances, which is practical with regard to storage, but does not require refrigeration, is easily handled by a physician, does not induce allergies or infections, does not cause cancer, and is biologically suitable And finally, low cost methods and compositions.

One of the main objects of the present invention is the removal of wrinkles, non-phrases, reduction of lip and contour of human skin, keratosis, enhancement of cheek area, reduction of bilobus, buttocks of hip area, natural aging or external factors ( Example: to provide novel methods and compositions for correcting dermatological defects such as senile spots and changes in the skin through the action of sunlight).

The compositions of the present invention can be applied just below the area of the skin where dermatological defects occur through injection of the composition.

The composition of the present invention is not substantially absorbed by the human body, and in turn, is not rejected by a person and does not cause an allergic reaction.

In addition, the method of injecting the composition according to the present invention can be applied easily and reliably, without the need to anesthetize the patient.

The present invention relates to methods and chemical compositions used for the purpose of correcting dermatological disorders. In particular, the present invention relates to the removal of wrinkles, non-phrases, reduction of the lip and correction of contours, keratosis, enhancement of the cheek area, reduction of the lobe of the hips, the inclination of the buttocks area, human aging or external factors such as It relates to a composition that is applied to correct dermatological defects such as senile spots and changes in the skin through the action of).

The composition according to the invention consists of a colloidal formulation called carboxy glyconate hydrolactic of magnesium.

This formulation consists of:

(a) about 5 to 70 g of cellulose ether;

(b) about 800 to 1300 ml of Ringuer lactate;

(c) about 2 to 20 g of EDTA;

(d) 20 to 120 ml calcium glyconate; And

(e) optionally 0-10% xylocaine.

The amount of components can vary within the optimum range until a suitable viscosity is obtained.

Among the polymers of ethers of cellulose, those having a low molecular weight or low viscosity are preferred as follows:

Hydroxymethyl cellulose,

Hydroxyethyl cellulose,

Hydroxypropyl cellulose,

Hydroxybutyl cellulose,

Hydroxypropylmethyl cellulose,

Carboxymethyl cellulose of sodium,

Carboxymethyl cellulose of calcium,

Methylcellulose and / or ethylcellulose.

Ringer lactate is an inert solution consisting of sodium chloride, potassium chloride, calcium chloride dihydrate, sodium lactate and water.

EDTA, called ethylenediamine trisodium tetraacetate trihydrate, is chemically inert and eventually suitable for medical use, apart from not being degraded in other materials, because it does not react with other chemicals in the compositions of the present invention or in the human body. to be. Its chemical formula is C ₁₀ -H ₁₆ -N ₂ -O ₈ · 3Na.

The method for preparing the composition of the present invention consists of mixing all the components in a stainless steel tube and then stirring them. The mixing temperature may vary for a period of about 4 hours at 30 to 70 ° C, preferably at about 50 ° C.

This method is repeated two more times until the final product is obtained.

In this step a colloidal solution is obtained.

The colloidal product obtained is then filtered and its pH is demonstrated to show a value of about 6.0.

The density of the product shows the same value as 1.

The product obtained, i.e., the carboxy glyconate hydrolactic composition of magnesium, which already has the required pH and density, is injected into 20 ml vials, labeled and ready for dispensing.

To illustrate the invention, animal experiments are performed. These experiments are based on the investigation of the reactions taking place in the tissues of animals after the application of the exogenous material according to the invention.

Experiment I

Comparative histological study of extracellular matrix and cellular changes obtained from injectable implants of carboxy glyconate hydrolactic colloid of magnesium in hypodermis of albino rats

In Experiment I, different possible tissue responses obtained from injection of carboxy glyconate hydrolactic of magnesium were evaluated in 108 groups of rats to obtain samples at 1, 2, 4, 8 and 16 weeks and the same conditions. The other 20 rats injected with a physiological solution of sodium chloride, which were maintained as a control, remained at the same conditions and served as controls.

Substances and Methods

72 adult Albino rats of the Wistar lineage were subjected to an electrical hair clipper selected on the middle vertebral line, two surgical stitches (1.5 cm between them), through the inhalation of ether tri-branched in the back (intrascapular region). The surface is anesthetized using an area placed sagittal with a black line). In the back, 36 first groups in the scapula area were injected with 0.5 ml of carboxy glyconate hydrolactic colloidal composition of magnesium, and the rats had three sterile plastic cages with a sterile wooden rice paddle and a bottom to feed them. 13 cm), allowing unlimited water penetration. 36 second groups were treated similarly, but injected with a physiological solution of sodium chloride and these rats remained under the same conditions to serve as controls.

After 1, 2, 4 and 8 weeks, 14 animals (7 injected with magnesium carboxyglyconate hydrolactic and 7 injected with physiological solution) were treated by deep anesthesia with ether. Next, fragments of the skin, kidneys, liver, spleen, heart and lung are removed and at the same time the primary lymph nodes are examined for growth in the actual histopathological studies if growth is found. At 16 weeks, the remaining animals are killed.

The fragments are fixed in a solution of 10% formaldehyde in PBS for 3 to 5 days and then they are washed in running water for 15 minutes. In addition, a second fragment of skin from the injected area was removed from each animal, fixed in a 5% paraformaldehyde solution in PBS for 4 hours for subsequent immunohistochemical studies, washed in PBS, and then fragments were Process in the same way as others for mechanical processing.

All fragments are then dehydrated in an increased concentration of ethanol solution, which is then impregnated, cleared by xylene, and finally included in paraffin. A cut of 5 μm is obtained using a Spencer 820 rotating microtome (American Optical Co.) and stained by hematoxylin-eosin technology after having previously been fixed on formaldehyde-PBS on a tissue slide. . The formulation can then be examined by Optiphot model Nikon microscope and coupled to an automatic AFX 11 photometer with a 35 mm camera, thus obtaining a micrograph on 100 ASA Kodacolor film from Kodak.

During the first phase of observation, in the first week, droplets of colloids (identifiable as amorphous and basophilic substances) were enclosed by mononuclear cells through the manifestation of the skin from animals injected with carboxy glyconate hydrolactic of magnesium, This can be observed to show strong infiltration in the scanning area around the appendage under the epidermis. At 2 weeks, infiltration persists and macrophages can already be observed around large multinuclear cells as well as droplets of colloids. At 4 and 8 weeks, macrophages show an initial capsule or infiltration between the colloidal droplets. Finally, at 16 weeks, macrophages, fibroblasts and binding matrix surround a collection of colloids and are still discernible by basophils.

In addition, imaging observations of fixed plasma contractions inside blood vessels proximal to the endothelial surface, which may be confused with the possible presence of fine microspheres in the blood, are in fact not confused as in the blood vessels of animals injected with NaCl. It also exists. No signs of tumorigenesis are detected in the fragment of skin studied.

From two weeks after the experiment, the colloid is already retained in the granuloma at the formation stage, which is present in a general way under the muscle, but can pass through the muscle layer to reach the dermis. These granulomas are retrieved until they form a sac containing a colloid still surrounded inside by macrophages. At week 16, the binding matrix can be observed as the portion of the binding capsule that encloses the granule tumor between macrophages and fibroblasts.

Results of Experiment I

From the observations of Experiment I, the injection of carboxy glyconate hydrolactic of magnesium in hypodermis of albino rats is preferentially localized at the injection site, i.e., in the internal part of the skeletal muscle layer of hypodermis (in rats), It can be concluded that it promotes the formation of granulomas in response to foreign bodies. However, in certain situations, it reaches the area above the muscles of Hypodermis, resulting in deep dermis. Such granuloma becomes stable at approximately two weeks, and after injection, the carboxy glyconate hydrolactic colloid of magnesium can be manifested in an apparently stable form surrounded by huge foreign cell. After 8 weeks, the granuloma is enclosed by a binding capsule that extends the septum inwards to convert the lobular granuloma. The presence of tumorigenesis is not observed.

Experiment II

Comparative histological study of extracellular matrix and cellular changes obtained from injected implants of carboxyglyconate hydrolactic colloid of magnesium of albino rats. Evaluation of matrix

In Experiment II, adult female albino rats of Wistar lineage are used.

This experiment II is an evaluation of tissue changes obtained from an implant injected with carboxy glyconate hydrolactic of magnesium in 108 albino rats, and carboxy glyconate hydro of magnesium in the intraspine scapula region previously tri-branched in these 108 rats. Inject with lactic. The other 20 rats were injected with a physiological solution of sodium chloride, which remained under the same conditions and served as a control.

Substances and Methods

The method used to obtain animal tissue is described below.

Albino rats are treated with deep anesthesia to remove fragments of the skin, kidneys, liver, spleen, heart and lungs. These fragments were fixed in a 10% formaldehyde solution in PBS at 4 ° C. for 3 to 5 days and then they were washed in running water for 15 minutes. All fragments are then dehydrated in an increased concentration of ethanol solution, which is then impregnated, cleared by xylene, and finally included in paraffin. 5 μm cuts are obtained using a Spencer 820 rotating microtome (American Optical Co.) and mounted on tissue slides and then stained by hematoxylin-eosin technology or by the Gomori tricolor method. The formulation can then be examined by Optiphot model Nikon microscope and coupled to an automatic AFX 11 photometer with a 35 mm camera, thus obtaining a micrograph on 100 ASA Ektachrome film from Kodak.

Samples are obtained at 1, 2, 4, 8, and 16 weeks from the tissues of rats to assess possible differences in tissue responses obtained from carboxy glyconate hydrolactic of magnesium.

Injection of carboxy glyconate hydrolactic of magnesium in albino rats preferably results in the formation of granulomas in response to foreign bodies, ubiquitous at the injection site, ie inside the skeletal muscle layer (present in the rat) of hypodermis. It is proven to promote. However, in certain situations, it reaches the area above the muscles of Hypodermis, resulting in deep dermis. Such granuloma becomes stable at approximately two weeks, and after injection, the carboxy glyconate hydrolactic colloid of magnesium can be manifested in an apparently stable form surrounded by huge foreign cell. After 8 weeks, the granuloma is enclosed by a binding capsule that extends the septum inwards to convert the foliar granulomas. The presence of tumorigenesis is not observed.

Micrographs show that when using the compositions of the present invention, a collection of droplets of carboxy glyconate hydrolactic colloids of magnesium having irregular shapes and representing basophilic components can form large populations or large foreign body cells between macrophages. It can be observed that it is surrounded by.

Injection of carboxy glyconate hydrolactic colloids of magnesium produces an inflammatory response at the end of the first week, filling the area with macrophages that infiltrate between droplets of amorphous and basophilic colloids, facilitating matrix deposition that can be seen well below the muscle layer, It is rich in reticular fibers, exhibited by green refractions equivalent to those of the surrounding and endometrium.

At 2 weeks, the macrophages already formed a thick layer around the collection of colloidal droplets and infiltrated between the colloidal aggregates, resulting in a diaphragm showing prolonged deposition of extracellular matrix enriched in thin to reticulated fibers and thick to collagen fibers. Form.

At 4 and 8 weeks, when injected with carboxy glyconate hydrolactic of magnesium, it can be clearly observed that it contains a basophilic substance (colloid) which forms an amorphous space and forms a separate aggregate. At 4 and 8 weeks, the preponderance of fibers with green birefringence is observed in the gaps of aggregates of colloidal droplets, which is compatible with the predominance of collagen III specific to reticular fibers.

At 16 weeks, it was observed that colloidal granulomas showed the predominance of green or birefringence in the gap with thin septum and yellow or red birefringence in the thick septum and capsule. This is due to the large amount of collagen III present in the gaps of the small septum.

Conclusion of Experiment II

From the observations of Experiment II, it can be concluded that injection of carboxy glyconate hydrolactic of magnesium in hypodermis of albino rats promotes the formation of granulomas in response to foreign bodies having the same properties as the extracellular matrix. The granulated tumor thus constructed becomes stable approximately 2 weeks after injection, and the colloid can be visualized in an apparently stable form surrounded by giant foreign body cells. Already, at one week, when infiltrating a colloid, the actual macrophages begin to promote diaphragmatic division of future granulomatous tumors, producing the first extracellular matrix. Granuloma at 2 weeks shows more advanced diaphragm splitting, and at 8 weeks, it has a highly viscous binding capsule enriched in collagen I that sends the septum inwards to make the mentioned granuloma apparently lobed. But inside the lobules, the abundance of collagen III is remarkable. Collagen III is so rich inside stabilized granulomas that tends to indicate the presence of thin binding fibers, and if collagen I-rich high viscosity binding fibers (collagen fibers) predominate, the state of fibrosis is not defined.

How to treat dermatological disorders

In accordance with the present invention, a method of treating dermatological disorders by filling and correcting non-aesthetic changes using a composition of carboxy glyconate hydrolactic of magnesium is described next.

The composition is obtained by the method already described herein, consisting of mixing all the components in a stainless steel tube and then stirring. The mixing temperature may vary between 30 and 70 ° C., preferably at about 50 ° C. for a period of about 3 hours.

This method is repeated two more times until the final product is obtained.

In this step a colloidal solution is obtained.

Next, the colloidal product obtained is filtered and its pH is demonstrated to show a value of about 6.0 and a density corresponding to one.

The resulting product, ie a composition of carboxy glyconate hydrolactic of magnesium already having the required pH and density, is injected into 20 ml vials.

In order to inject the product, it is first essential to identify the areas to be treated and, if necessary, to label those patients who are upright first. Next, if the area to be treated is the ventral part of the head, the patient is placed on the spinal vortex at an angle of 45 to 60 ° from the seated position, or if the area to be treated is the vertebral area, the abdominal is not necessary.

Next, aseptic methods and preservatives are carried out using conventional preservatives.

Typically, blocking or even topical infiltration with preservatives is performed very comfortably during the procedure and with less stress on the patient.

Since the product is inert and biologically compatible, i.e. exempt from allergic or toxic reactions, no prior testing is necessary. Formation of the composition according to the invention prevents contamination by fungi or bacteria.

The contents of the vial are aspirated using a needle or cannula with tetragonal junctions. The size of the needle or cannula varies depending on the amount necessary to fill the area to be treated.

Application of the composition of carboxy glyconate hydrolactic of magnesium is carried out using a needle or cannula depending on the area to be treated.

Injection of the composition prevents the formation of sequential bubbles, such as pearl necklaces, because in this way the results are irregular.

For permanent implants, light calibration is performed, where necessary one or more compensation periods can occur, with a 25 to 30 day interval between each period. In order to obtain better results in overall safety, this time interval is set for further injections. This spacing is fundamental to the deposition of collagen and fibrin fibers and provides the support necessary for microtransplantation.

Claims (6)

(a) about 5 to 70 g of cellulose ether; (b) about 800 to 1300 ml of Ringuer lactate; (c) about 2 to 20 g of EDTA; (d) 20 to 120 ml calcium glyconate; And (e) a colloidal composition for aesthetic correction, characterized in that it consists of a colloidal formulation called carboxy glyconate hydrolactic of magnesium, optionally consisting of 0-10% xylocaine. The ether of cellulose according to claim 1, wherein the ether of cellulose is hydroxymethyl cellulose, hydroxyethyl cellulose, hydroxypropyl cellulose, hydroxybutyl cellulose, hydroxypropylmethyl cellulose, carboxymethyl cellulose of sodium, carboxymethyl cellulose of calcium, methylcellulose And / or a polymer of an ether of cellulose selected from ethylcellulose. The colloidal composition of claim 1, wherein the Ringer lactate is an inert solution consisting of sodium chloride, potassium chloride, calcium chloride dihydrate, sodium lactate, and water. In humans, skin removal through the removal of wrinkles, nasal passages, reduction of lip and correction of contours, keratosis, enhancement of the cheek area, reduction of the lobe area, depression of the buttocks area, associated with natural aging or through the action of external factors such as sunlight A composition according to claim 1, which is applied to correct dermatological defects such as senile spots and changes. (a) mixing ether of cellulose, Ringer's lactate solution, EDTA and calcium glyconate; (b) the components of step (a) are stirred for a time of about 3 hours at a temperature varying between 30 and 70 ° C; (c) repeating the method of step (b) twice; (d) filtering the product obtained in step (c); (e) adjusting the pH of the filtered product to a value of about 6.0. 17. A method of making a colloidal composition for aesthetic correction. 6. The method of claim 5, further comprising the addition of xylocaine as an optional component.