SE433173B - Ointment base for the preparation of skin creams with high moisturizing effect - Google Patents

Description

7812512-7 10 15 20 25 30 35 A cream made up solely of fats can be completely absorbed into the skin but in some cases still leave a dry skin, as the skin must also be supplied with water to maintain its elasticity.

The horny surface layer of the skin consists of scaly cells that have lost their cell nuclei and therefore have acquired a keratin character. As long as this * layer of dead cells remains soft and elastic, it protects the underlying tissues from dehydration.

As it itself dries and cracks, the air can gain access to the underlying, vital parts of the skin.

Due to this, in addition to fats, ointment bases must also contain distilled water or water-releasing substances and wetting agents such as glycerol and other polyols.

The main task of moisturizers that are added to skin creams is to slow down the water release from the product and thereby prevent rapid drying of it, partly in cans and the like that are left open, and partly after application to the skin.

However, they are not able to create and maintain a reversible balance between the humidity and the moisture content of the cream, and can therefore not prevent the preparation from drying out, but only prolong this process.

The invention is based on the surprising discovery that an addition of between 0.6 and 15% by weight (preferably between 1 and 10%) of microfibers of a thermoplastic material with a very high specific surface area can significantly delay dehydration. of creams without this additive affecting other functional properties of the cream. The microfibers used according to the invention with a special morphology are prepared according to Italian patents 995 549, 963 620 and 1963102.

In order to illustrate the invention for a better understanding thereof, without this therefore implying any limitation thereof, Tables 1 and 2 list some different formulations of ointment bases for dermatological use and Table 3 their water holding capacity. expressed as the weight loss after certain specified time intervals of layers of these ointment bases with a layer thickness corresponding to the mass / surface unit values given at the bottom of the table.

Table 3 clearly shows that the preparations containing microfibers, despite a lower content of wetting agent, can show significantly lower values for water loss even during long test times.

It is clear, and this constitutes another aspect of the invention, that the addition of active ingredients, possibly. Medicinal active substances, for microfibers manufactured in accordance with the above patents, can give creams containing such microfibers a lasting medicinal or protective effect.

The active substances absorbed into the microfibers (mixed, occluded) are released from the cream in a well-controlled, regular manner, so that the effect of the cream on the skin remains constant over time - an obvious benefit for both medical and cosmetic preparations.

Through a suitable combination of this effect and the lasting moisture supply and moisture-retaining function, very significant qualitative advantages can be achieved.

To illustrate this aspect of the invention without thereby limiting its application, a series of experiments performed with ointments based on an ointment containing a certain content of hydrocortisone, which have been added either as a discrete product or mixed with microfibers of the the types listed above. 7812512-7 Table 1 (quantity in grams) Preparation A Preparation A 'Carboxymethylcellulose 85 95 Glycerol 50 55 5 Distilled water 765 850 Microfibers _ 100 - Preparation B Preparation B' Carboxymethylcellulose 20 22 10 Polyvinyl alcohol 40 44 Vaseline 300 334 Distilled water 540 100 - 15 Preparation C Preparation C Carboxymethylcellulose 10 12 Polyvinyl alcohol 40 42 Glycerol 450 473 Distilled water 450 473 20 Microfibers _ 50 - Preparation D Preparation D 'Preparation D "Carboxymethylcellulose 23 22 25 25 Glycerol l84 180 200 Dest. Water 713 698 775 Microfibers 80 100 - 10 15 20 25 30 Table 2 Carboxymethylcellulose Glycerol Distilled water Microfibers Carboxymethylcellulose Glycerol Distilled water Microfibers Polyacrylic acid Ethanol Glycerol Triethanolamine Distilled water Microfibers Polypropylene glycol stearate Paraffinolate Water Paraffinolate quantity indications in grams) Preparation E Preparation E '48 52 190 200 712 748 50 - Preparation F Preparation F ”76 79 194 200 710 721 20 - Preparation G Preparation G' 9.9 10 149.0 150 198.0 200 19.8 20 617.3 620 60 - Preparation H Preparation H '178 180 78 80 1 l 733 739 10 - Preparation I Preparation I' 148 150 198 200 644 650 10 - o_H mm m_o mo m_o mo mm m_H mm NH mm oH mo mH mH m, H mm> . ~ m. ~ a \ m Table 3 uwncmuæwmmwmz mm mm Nm mm ~ \ H m mm mm mm Nm N \ H m mm mm m Nmm mm Hm mm N \ H. ~ mm mm Nm Hm m N mm Nm Nm mm mm mm N \ HH mm mm mm mm om Nm om mm mm mm mm m H m mm mm mm mm ~ \ H Avm flfl n fi ßm fl wßunmuvv .m flflfl v fl w flflfi ßv fifl kw .om HMEEHU TDHB \ HH \ mm 1w w \ mm \ mm \\ Q \ nn \ oo \ The experiments have been performed to evaluate the release of the medicinal substance in the cream and have been of two kinds, partly in vivo by evaluating the vasoconstriction of the hydrocortisone vasoconstrictor. effect, which manifests itself as a decrease in skin temperature, partly in vitro by measuring the diffusion of the active substance from the cream into an ambient solvent, carried out by determining the amount of the substance present in the solvent after certain time intervals.

In the manufacture of the creams, three types of microfibers were used, made from: l. High density polyethylene (PA l / 1); Modified HD polyethylene, containing a hydroxyl group (PA 1/2); and 3. Low density polyethylene (PA 1/4).

The creams used in the experiments consisted of gels or ointments. The following ointment base was used for the gels: Polyacrylic acid (Carbopol 934 for pharmaceutical use) 10 g Ethanol 150 g Glycerol 200 g Water 620 g Triethanolamine, q.s. for the desired pH value.

The gel was prepared in a conventional manner: Carbopol was dispersed with stirring in a mixture of ethanol and glycerol. When a homogeneous mixture was obtained, water was added with gentle stirring to limit agitation of air. The gel was allowed to stand for about 48 hours, after which the active substance was added, separately or in bulk to the microfibers, by mixing in a mortar or in a slow-moving planetary mixer.

The following bases were used for the ointments: A: Polypropylene glycol stearate 18 g Paraffin oil 8 g Sodium methyl paroxybenzoate 0.1 g Water 100 g 7812512-7 10 15 20 25 30 8 B: Mixture of fatty alcohols and polyoxyethylene alcohol 15 g Glycerol 20 g Water 100 g The fatty substances melted to a homogeneous mixture, after which the water was added in small portions until all the water was taken up and the mixture was allowed to cool at about 20 ° C for about 12 hours. After homogenization, the active substance was added in a slow-moving planetary mixer, either separately or mixed in microfibers. For the preparation of the hydrocortisone-containing microfiber pulp, a hydrocortisone solution was prepared, in which the microfibers were dispersed in an Ultra-Turrax disperser. After filtration at atmospheric pressure, the mixture was allowed to dry to a mass containing the active substance. The uptake of the hydrocortisone from the solution was practically complete. In the sample preparations for the experiments, 0.6 g of hydrocortisone per 0.4 g of microfibers was used, and the addition of the microfibre mass so prepared to the ointments was adjusted so that a final content of 1% of hydrocortisone was obtained.

The in viva experiments were performed on both guinea pigs and humans. For this purpose, the gel or ointment was applied to the skin under tight bandages, and the skin temperature was measured telemetrically.

Since it was impossible to keep the bandages on trial for a longer period of time, no tests could be performed with them for longer than a few hours. The test results are reported in Table 4. 10 15 20 25 30 35 7812512-7 Table 4 - Temperature changes in the skin after application of hydrocortisone ointment without / with microfibers.

Time from application, h 2 4 6 Temperature change, OC Control experiments with untreated guinea pigs O 0 - 1 Gel without microfibers - 1 - 3 - 5 Gel with microfibers - 0,5 - 2 -, 5 - 1,5 - - - 0 , 5 - 2,5 Ointment A without microfibers - l 0,5 - 1 Ointment A with microfibers 0 - 1 - 1,5 - 0,5 - 1,5 - 1,5 Ointment B without microfibers - 2 - 2 - 1 , 5 - - - 3 Salva B with microfibers 0,5 - 1 - _ ._ 2 _. Although the results are not absolutely unambiguous, probably due to the difficulty of getting the bandages to sit on the experimental animals, it is clear that ointments with microfiber additive have an effect that is somewhat delayed compared to ointments without microfibers.

The trials in humans show a consistent delay in the vasoconstrictive action of hydrocortisone for creams containing microfibers of the types used, and at all the pH values of the preparation examined. 1812512-7 lo Table 5 - Mean value of temperature change in the skin for patients treated with hydrocortisone gel without / with microfibers, pH = 6.8. 5 Average temperature change 1 ° c after: 5 h G24 n 48 h 72 h Without microfibers; -1.5 -1.7 -1, 3- -0.75 10 With microfibers: PA 1/1 -2 -1.25 -1.25 -0 PA l / 2 -1.5 -1.75 - 1.25 -1.5 PA l / 4 -0.5 -1 -2 -1.25 Table 6 - Mean value of skin temperature change for patients treated with hydrocortisone gel without / with microfibers, pH = 4.2. Average temperature change 1 ° C after; 5 h 24 h 48 h 72 h Without microfibers: -1.25 -l -1.5 -1.3 f With microfibers: 25 PA l / 1 -2 -1.75 -1.5 -0 PA l / 2 -0.5 -0.5 -1.75 -1 PA 1/4 -l -1.5 -1.5 -1.5 Table 7 - Mean value of temperature change in the skin for patients treated with hydrocortisone gel without / with microfibers, pH = 7.8.

Average temperature change 1 ° c after: 5 h 24 h 48 h 72 h Without microfibers -1.25 -1.7 -1.5 -1.35 With microfibers: PA 1/1 '-1 -1.5 -2 -1.5 40 PA 1/2 -2 -2 -1 -1 PA 1/4 -1 -2.5 -1.75 ez 10 15 20 25 30 35 7812512-7 ll In vitro experiments were performed in Paulson vessels according to Figure 1, where 1 is a stirrer (30 rpm); 2 is a thermostatically controlled bath (37 ° C); 3 is the solvent (here about 200 ml of isopropyl myristate); and 4 is a Petri dish containing about 20 g of the preparation in gel form.

The petri dish with the preparation was immersed in the solvent, after which the stirrer was started and a sample of 1 ml was taken out of the solvent every hour for seven hours. The samples taken were checked for diffuse hydrocortisone content by colorimetric analysis of tetrazole blue in methanol.

The optical density at 525 nm wavelength was measured with a spectrophotometer and the corresponding diffused amounts of active substance were determined by comparison with a calibration curve.

The results of the tests are presented in Figures 2, 3 and 4, which illustrate the diffusion into the solvent of hydrocortisone from four gels with different pH values, resp. 4.2; 6.8; 7.8; all containing 1% hydrocortisone, free or physically bound to microfibers of the types described above.

The measuring points dotted in the diagrams refer to the different gels as follows: Q are measuring points for gels without the addition of microfibers; x are measuring points for gels with microfibers type PA l / 4; o are measuring points for gels with microfibers of type PA l / 2; and O are measuring points for gels with microfibers of type PA 1/1.

In all three diagrams, an initially reduced hydrocortisone diffusion can be clearly observed for gels with microfiber additive, implying a marked delay in the release of the active substance as it is bound to the microfibers.

Claims (3)

7812512-7 Patent claims 1. l. Ointment base for the preparation of skin creams with a high moisture-retaining effect, characterized in that it contains between 0.6 and 15% by weight of microfibers of a thermoplastic material with a very high specific surface area. Ointment base according to claim 1, characterized in that the content of microfibers is between 1 and 10% by weight. Ointment base according to claim 1, characterized in that the microfibers contain active substances bound to them with medicinal action.