RU1809759C - Lubricant - Google Patents

Abstract

The invention relates to medicine, namely experimental medicine, traumatology and orthopedics, and can be found. the use in the development and testing of new drugs aimed at restoring the normal functioning of joints affected by arthrosoarthritis. The purpose of the invention is to reduce friction of articular surfaces. Essence: new in the method is the introduction of a lubricant preparation, which uses cholesterol compounds realizing a liquid crystalline state in the temperature range corresponding to the transition temperatures from solid to liquid crystalline not more than 35 ° C, and from liquid crystalline to isotropic liquid less than 38 ° C to the contact area of the cartilage surfaces (CCP). Moreover, liquid crystal preparations are preliminarily added either to solutions of high molecular weight compounds, which are used as a 0.5–2.5% aqueous solution of sodium salt of carboxymethyl cellulose (Na-CMC), and 0.5–2.5% solution of Na-CMC in hemodesis (aqueous solution of polyvinylpyralidone and mineral salts) in an amount of 0.5-1.5 May. %, which are injected into the region of CCP, or in medical oils in an amount of 8-10 wt%, and the intake of P in the region of CCP is carried out by diffusion by means of applications (A) of the obtained mixtures to the area of the affected joint, and A is carried out 1 once a day with the application of a warming dressing and repeating the procedure at least 5-7 times. New in L is the use of LC CX as organic compounds, for example, cholesteryl palmitate (3-15 wt.%), Cholesteryl petrosolate (15-35 wt.%), Cholesteryl linoleate

Description

The invention relates to medicine, namely experimental medicine, traumatology and orthopedics, and can find application in the development and testing of new drugs aimed at restoring the normal functioning of joints affected by arthrosoarthritis.

The purpose of the invention is to reduce friction of articular surfaces.

For the implementation of the method, a liquid crystal preparation is used in the form of cholesterol compounds or from a mixture pea-1 lysing a liquid crystal state in a temperature range including

 w

physiological temperatures of living organisms.

The specific compositions of the liquid crystal preparation are given in table 1.

As can be seen from Table 1, the compositions (2-4) possess a liquid crystal state in the temperature range, including the physiological temperatures of living organisms.

The addition of these liquid crystal formulation compositions to carbon solutions of hydrogen-containing compounds was carried out as follows.

Example 1. Preliminarily, at room temperature, 0.5-2.5% of sodium carboxymethyl cellulose sodium salt was added to distilled water. The result is an aqueous solution of the sodium salt of carboxymethyl cellulose, the viscosity of which depends on the content of the water-soluble polymer in it. Then, an aqueous solution of the sodium salt of carboxymethyl cellulose and the required amount of a preparation realizing a liquid crystalline state (0.5-1.5 wt.%) Are heated in an oven to a temperature of 70-90 ° C. After melting and transferring to an isotropic liquid, the liquid crystalline preparation is added to the aqueous solution of the sodium salt of carboxymethyl cellulose with continuous stirring of the latter using an electric stirrer. After the liquid crystal preparation is evenly distributed in an aqueous solution of sodium salt of carboxymethyl cellulose, the heating is stopped and the resulting mixture is cooled at a rate of 2-3 deg / min while the stirring process is continued until it is cooled to room temperature. The result is a mixture, ready for use as an injection.

Example 2. The preparation of a mixture of a solution of hydrocarbon-containing compounds and a liquid crystal preparation was carried out under conditions analogous to Example 1, but carboxymethyl cellulose (0.5-2.5 wt.%) Was added to the hemodez.

Example 3. A preparation realizing a liquid crystalline state (8-10 wt.%) Is preliminarily added to medical oils (petrolatum, castor, silicone). Then, the resulting mixture is heated to 70-90 ° C and after cooling, a ready-to-use composition is obtained in the quality of applications.

The rheological properties of the samples, normal synovium, and solutions of hydrocarbon-containing compounds with a liquid crystal preparation intended for injection were studied at 24 ° C on a Reotest2 viscometer. The results of these studies are presented in Table 2.

As the studies showed, the best resemblance to the rheological properties of natural synovium are in the formulations - (2-4), the ingredients of which are the sodium salt of carboxymethyl cellulose, a liquid crystal

0

the drug and distilled water as well

formulations (7-9), the carboxymethyl cellulose sodium salt, a liquid crystal preparation, and hemedes are used as ingredients.

5 Tribological studies were carried out using a matrix tribometer, because it implements the precomposition characteristic of a natural joint.

Samples for friction were made from

0 heads of the humerus (the convex part) and the articular cavity of the scapula (the concave part) of animals 1-2 hours after their face. For each experiment, at least three samples were prepared, cartilage from the underlying bone

5 not deleted.

The friction force was judged by the damping time of the oscillations of the pendulum, as well as the angle of inclination to the abscissa of the dependence of the amplitude of the oscillations on time. The initial amplitude of oscillations and in all experiments remained constant. Before testing, 1 cm3 of lubricant is introduced into the test composition.

Analysis of the results presented in

5, Table 3 shows that the introduction of 1 wt.% Liquid crystal preparation into the aqueous solution of sodium salt of carboxymethyl cellulose provides the same friction value as the synovial fluid with

0 lower total cholesterol (options 5.6). A significant reduction in friction is also observed for haemodesis containing a liquid crystal preparation (option 4).

5 It was noted that for a synovial medium with an increased cholesterol content, the decay time of the pendulum is increased (option 7). Hence, according to the results presented in Table 3, it is obvious that the introduction of a liquid crystal preparation, i.e. a preparation based on cholesterol compounds realizing the liquid crystalline state of the lubricant and inherent in natural synovium, into known preparations for the therapeutic correction of joints lead to a significant improvement in their tribological properties.

Thus, the above studies indicate that the proposed 1 liquid crystal

cholesterol compounds are the real basis for drugs for the therapeutic correction of the tribology of affected joints, which are advantageously administered by intra-articular injection.

Therefore, in addition to the experiment on 10 male rats of the herd breeding from the Leningrad experimental nursery of the USSR Academy of Medical Sciences, Rappalovo, the effect of these liquid crystalline cholesterol compounds on articular cartilage in adjuvant arthritis was studied. From the studied joints of animals, total histological preparations were made in the sagittal plane, which were stained with hematoxylineosine. It was established that in the control group there was unevenness of the width of the cartilage cover, heterogeneity of color (metrochromium of the main substance of the cartilage), razvolokanie surface of the cartilage along the outer edge, in some places its fragmentation and the presence of patterns filled with connective tissue. After the introduction of liquid crystalline cholesterol compounds in the experimental group, the same width of the cartilaginous cover was everywhere preserved, uneven distribution of cellular elements, pale color of the interstitial substance were observed, however, dystrophic changes were less pronounced than in the control group. This picture testified to the protective role of liquid crystalline cholesterol compounds when they were introduced into the friction zone of the Tatologically altered cartilage.

Considering that it is proposed to transport liquid crystal substances to the affected joint through the skin. Additionally, in the animal experiment, the diffusion ability of cholesterol FSW through the skin and the possibility of their intraarticular transport were studied. For this, 26 male rats of the herd breeding from the Leningrad experimental nursery of the USSR Academy of Medical Sciences Rappalovo weighing 265-290 were taken. Animals were divided into 2 groups. In the first (12. rat) diffusion of cholesterol FSW was studied under physiological conditions . In the second (12 rats) group, arthritis of the joints of the left lower limb was modeled by introducing 0.1 ml of Freund's adjuvant under the plantar aponeurosis.

The studies used 8-10% solutions of liquid crystalline cholesterol compounds in medical oils (liquid paraffin, castor, silicone), since the latter are widely used in medicine and do not give side effects.

The test drug was a mixture of the proposed cholesterol FSA labeled with 1.23 N (drug activity 7.5 ± 0.5 min) with paraffin oil. The animals received daily applications of freshly prepared preparation on the left knee vain area in an amount of 0.5 ml with an exposure of 60 minutes under hydroxybutyran anesthesia.

Samples of the following tissues were studied: blood, liver, kidneys, anterolateral portions of the capsule of the left knee joint and articular cartilage of the femur condyles. The radioactivity of the preparations was determined by liquid scintillation method on a Mark-3 instrument from Searle (Holland).

The results of the study of specific radioactivity under physiological norms (group 1) and with adjuvant arthritis (group 2) are presented in Table 4. They indicate the presence of intraarticular transport of FSW cholesterol during diffusion through the skin, and with adjuvant arthritis, the diffusion ability of the drug was higher.

Therefore, the above studies convincingly indicate the high diffusion ability of cholesterol FSW through the skin in the area of the affected joint, and therefore are the real basis for drugs for the therapeutic correction of the tribology of degeneratively changed joints introduced into the contact area of the cartilage through diffusion.

Thus, the above experimental studies convincingly show that the proposed method due to the versatility of the forms of use, namely: the possibility of using both injections and applications because of the high diffusion ability of the cholesterol cholesterol, as well as the intended antifriction purpose of the latter, leading when they enter the contact area of the cartilage to the implementation of the friction mechanism and wear of the inherent natural synovial environment of the joints, they have increased efficiency in knowledge of known methods and drugs for the treatment of degenerative joint diseases.

Forumul and zobret n and 1. A method for the treatment of degenerative-dystrophic diseases of sustaina by

the introduction into the joint of drugs containing an aqueous solution of polyvinyl pyrrolidone, characterized in that, in order to reduce friction of the articular surfaces, a mixture of cholesterol compounds is used, for example, in the following ratio (wt.%) of cholesteryl palmitate is 3-5; cholesteryl petrozelate - 15-35; cholesteryl linoleate - 15-25; cholesteryl oleate - 100, at a transition temperature from solid to liquid crystalline not more than 35 ° C, and from liquid crystalline to isotropic liquid not less than 38 ° C, and first liquid crystalline cholesterol compounds are added to the solutions of hydrocarbon-containing compounds in an amount of 0.5- 10.0 wt.%.

2. The method according to claim 1, characterized in that as solutions of hydrocarbon-containing compounds, a 0.5-2.5% aqueous solution of sodium salt of carboxymethyl cellulose is used, wherein a mixture of cholesterol compounds is added from 0.5 to 1.5 %

3. The method according to PP. 1 and 2, with the exception that in the quality of a solution of hydrocarbon-containing compounds, a 0.5-2.5% solution of sodium salt of carboxymethyl cellulose in hemodes is used.

4. The method according to claim 1, wherein the liquid crystal cholesterol compounds are added to medical oils in an amount of May 8-10. % and used for applications.

Table 1

table 2

Table ItzaZ

Joint lubricant test results on the motherboard tribometer

Option

Hemodez

15% aqueous solution of PVP (1) 2% aqueous solution of sodium salt of carboxymethyl cellulose Hemodez + 1% liquid crystal preparation

2% aqueous solution of sodium salt of carboxymethyl celluloea + 1% liquid crystal preparation

Synovial fluid with total cholesterol

0.9 mmol / l

Synovial fluid with a total cholesterol content of 4.09 mmol / l

Table. 4

The results of a radioisotope study of the diffusion ability of LCS cholesterol labeled with 1.23 N through the skin of rats under physiological conditions (1 g) and

with adjuvant arthritis (2 g.)

The time of complete damping of the oscillations of the

42

49

57

65

72

70

86