Artificial synovial fluid

 

(57) Abstract:

The invention relates to the field of medicine and relates to the synovial fluid. Goal is to improve lubricity. The essence of the invention lies in the fact that the artificial synovial fluid contains a mesogenic esters of cholesterol, sodium carboxymethyl cellulose, gemodez, the components contained in a given volume. As mesogenic esters of cholesterol use a mixture of acetate cholesterol, pelargonate and cholesterol oleate. 1 C.p. f-crystals, 2 tab.

The invention relates to medicine, namely for the treatment of rheumatoid arthritis and osteoarthritis.

Rheumatic joint diseases, in particular rheumatoid arthritis and osteoarthritis deformans, is a pathological change all parameters of the synovial environment. Decreases the amount of change in composition, rheological properties, which leads to a sharp increase in friction coefficient and wear of the cartilage surfaces. This causes a sharp pain, headaches, decrease in range of motion in the joint.

Currently Arsenal artificial means for injection into the joint, capable of at least partially simulate this on the fir liquids [1] However, these studies have not yielded significant results and had no statistical significance. Minor positive effect was obtained when using silicone fluid with a viscosity of 300 cSt due to the fact that the rather high viscosity of the lubricant was provided by the division of the surface of the cartilage relative to each other and, therefore, contributed to the reduction of wear and pain in patients. But at the same time increasing the viscosity of the lubricant inevitably entailed high shearing forces, which may be undesirable for the affected joints.

In [2] discusses the use as a lubricant for joints long chain polymers that are soluble in the liquid. In particular, we are talking about applying for these purposes, the polyethylene oxide. It is highly soluble in water, has a sufficiently high molecular weight, allowing in small concentrations to obtain a fairly viscous solutions. Microsemi polyethylene oxide, frozen on a glass slide under load, find the similarity structure of synovial fluid in the same conditions. However, thermo-mechanical destruction of such lubricants is not possible to use them in the joints due to the sharp drop in the viscosity of the substance, leading to deterioration egoia closest to the technical essence and the achieved result to the invention is an artificial synovial fluid (coli) for the treatment of rheumatoid arthritis and osteoarthritis aqueous solution of polyvinylpyrrolidone (PVP). This drug is able to temporarily compensate for a deficiency of Zinovii, to have anti-inflammatory and lubrication action to improve metabolism in articular cavity [3] currently, 15% aqueous solution of PVP is allowed for clinical use.

However, with a number of advantages of the drug on the basis of PVP inherent drawbacks: the constancy of rheological properties and viscosity mismatch natural Zinovii. 15% PVP solution has a viscosity of 1.8 srvc.ed. and natural synovial fluid 3,1 srvc.ed. [4] Synovial fluid capable of load-dependent change in viscosity, due to the squeezing out of her low-molecular components and their penetration into the cartilage tissue [5] This is not typical drug-based PVP. The lack of effect of viscosity changes under the influence of a load of drugs on the basis of PVP leads to a rapid conclusion it from the glenoid cavity [6] low lubricity. So when the friction of cartilage in the presence of coli-based PVP is implemented, the friction coefficient is not lower than 0,08 [7] and joints healthy person have a coefficient of friction of 0.001 and 0.03, i.e. an order of magnitude lower [8] mismatch between the pH of aqueous pH of a 15% aqueous solution of PVP is 5.2-7,0% [4] and the pH of natural Zinovii of 7.4 to 8.2% similarity to the mineral composition, structural-rheological, friction and alkaline properties of natural Zinovii, i.e., increase lubricity.

This objective is achieved in that a coli, according to the invention, contains gemodez (aqueous solution of PVP and mineral salts), sodium carboxymethyl cellulose (Na), mesagerie connections cholesterol esters (OH) mesophase 28-66aboutWith, including the temperature of a living organism, in the following ratio, wt.

Natrocarbonatite - cellulose 0,8-1,0

Mesogenic compounds of esters of cholesterol 0,5-0,8

Gemodez (water

a solution of PVP and mineral salts) Else

The choice gemodeza as the basis coli, due to the fact that he is an aqueous solution of PVP and a set of mineral salts present in natural Zinovii. Given that the well-known drug, which is a 15% aqueous solution of PVP, is the coefficient for the pair of friction of cartilage-cartilage is significantly higher than when the lubricant gemodeza, then later as the basis coli was used in its standard formulation.

The invention is based on the following facts:

1. Studies have established the presence in the synovial fluid of human and animal management as a substitute for blood plasma, the prolongator simultaneously introduced drugs and anti-inflammatory medication.

3. Additive mesogenic compounds EH with mesophase 28-66aboutWith the solutions gemodeza and Na provides for lubrication of the cartilage surface friction characteristics, such as natural synovial fluid. Studies have shown that a mixture of mesogenic OH (acetate cholesterol, pelargonate cholesterol and cholesterol oleate in the ratio of 10, 30, 60 wt. respectively) provides the most consistent composition EH natural Zinovii, and the interval of existence of the mesophases of this mixture 28-66aboutIncludes a temperature of a living organism, which is a necessary condition for high antifriction characteristics coli [10]

4. An aqueous solution Na, gemodeza and mesogenic OH have rheological, alkaline properties similar to natural Zinovii (PL. 1).

Na has many properties similar to those of hyaluronic acid, which is a component of natural Zinovii. Na long chain polymer class of polysaccharides, with small concentrations of highly soluble in water, structural formula Na CMC and hyaluronic acid are comparable. The percentage Na in coli provides viscosity, pH, specific who had tested in the treatment affected by osteoarthritis and rheumatoid arthritis of the joints of rats and rabbits have yielded positive results. No adverse events noted.

Thus, created a new synthetic fluid for treatment of joints, which simulates on mineral composition of natural synovia, and friction, flow, alkaline properties, it is identical due to the implementation of the system gemodez, Na, OH synergies and syneresis. Evidence of this are the studies of the lubricating ability of the proposed formulations coli in relation to natural Zinovii (PL.2).

As the lubricants used coli based gemodeza at various ratios mesogenic OH and Na (PL.1).

The compositions were prepared as follows. The necessary amount of gemodeza was dissolved, according to the recipe, a portion Na within hours, the composition was heated to 70-80aboutWith, then added the addition of esters of cholesterol in the molten state (melt temperature 66aboutC). The mixture was intensively mixed at slow cooling to room temperature.

Friction testing of such systems was carried out on a specially designed machine mechanical friction. The machine provides the sensitivity of the measurement of the friction force, respectively 0,025 N, 0,05 N 0,25 N. Is the range of 0.002 to 0.2 in the load range of 0.2-10.0 MPa. Test a pair of friction was carried out according to the scheme cartilage-glass at a sliding velocity of 0.1 m/c in the load range of 0.2 to 8.0 MPa. The load is changed stepwise. As the glass samples used in Petri dishes with a diameter of 0.1 m Samples of cartilage were cut from the knee animals and had dimensions 0,h,h,004 m When this cartilage was fixed, and the Petri dish with the investigated liquid revolved.

Increase the statistical significance of the experiments was achieved in the following way: two elastic menisci one joint were cut eight samples. Each of the eight samples were tested in all of the investigated liquids. The first sample of the first fluid, the second second, and so on, For tests taken eleven pairs of meniscus of cattle. This approach to the experiment were deliberately excluded errors that could occur due to different quality of cartilage.

In these experiments used natural joint fluid of cattle, taken immediately before the experiment.

There is no doubt that at least the dependence of friction coefficient on load for the proposed liquid and sinovia is provided by structural and rheological properties and active interaction IU is Ogien and the nature of changes in coefficient of friction. At the same time, coli prototype has a value of friction coefficient is 2 times more.

The effect of reducing the friction of adjacent cartilage called systems is confirmed by the results of studies with a pendulum tribometer, which is the most appropriate for these purposes, because it implements locomotion characteristic of joints in vivo.

According to its anatomical structure for research using pendulum tribometer is most suitable shoulder joint. Samples for friction produced from the head of the humerus (convex portion) and the glenoid of the scapula (concave part) of animals after 1-2 h after slaughter. For each experiment produced no less than 3 samples (cartilage from the underlying bone is not separated).

It is known that the greatest degree of severity of joint damage is the flow of synovial fluid in the zone of the cartilage mates, resulting in "dry" joints.

In order to simulate the "dry" joints before testing, all samples were kept in distilled water for 24 h, and then dried using filter paper and felt, bypassing the stage of storage.

The humeral head was sealed with a pendulum and ultaneously change the mass of the pendulum by means of a calibrated loads. For comparability of research results in all experiments, the area of contact of the cartilage was set constant and was estimated by the method of transfer upon contact of the water-soluble paint from previously painted surfaces cartilage on unpainted it is associated with cartilage. On the friction force was tried in the decay time of the oscillations of the pendulum and the angle to the x-axis according to amplitude fluctuations from time to time". The initial amplitude of the oscillations in all experiments remained constant for each of the lubricant pairs cartilage-cartilage.

Found the decay time of the amplitude and the mean square error.

Before the test in the test joint was injected 1 cm3a lubricant. As a last used the composition N 7 OH content of 0.5 wt. natural synovial fluid, a 15% aqueous solution of PVP and gemodez.

Thus, predlagaemy composition coli due to the manifestations of the system gemodez + Na + OH synergies and syneresis provides mineral composition, structural and rheological properties and pH identical to natural Zinovii, improves metabolism and has anti-inflammatory effect.

L I t e R a t u R e

1. Dowson d, Wright V. Thecartilage surface. Annals of the Pheumatic Discases 1975. Vol. 34 Suppl. p.p. 100.

3. Artificial synovial fluid for intra-articular treatment of rheumatoid arthritis and osteoarthritis (Development, clinical-experimental and biomechanical rationale) Therapeutic archive. 1984, No. 11, S. 73-77.

4. Vasilenkaitis centuries Clinical-biomechanical basis of intra-articular application of artificial synovial fluid in osteoarthritis deformans. Tr. Institute of experimental and clinical medicine of the Ministry of Lit.SSR, vol. XVIII, 1983, 124 S.

5. Pavlov C. N. Synovial environment of the joints. M. Nauka, 1980, 124 S.

6. Biopolymers, functional macromolecules rheumatoid and arthritic articular environment and rationale for some of its rheological methods and medicinal correlation. So research Institute of experimental and clinical medicine of the Ministry of Lit.SSR, vol. XIII, 1973, S. 523-541.

7. "Oiler" for the joint. Inventor and innovator, N 8, 1985, S. 16-17.

8. Moore D. Fundamentals and applications tribonacci. M. Mir, 1978, 488 S.

9. Synovial fluid and the value of its investigation in the diagnosis of joint diseases. Questions rheumatism. 1974, N 4.

10. Kopchenov B. I. p. etc. To the question of the mechanism of functioning of the joint, kicesie liquid crystals in clinical medicine. Journal of the all-Union chemical society them. D. I. Mendeleev. so XXVIII, No. 2, 1983, S. 68-75.

1. ARTIFICIAL SYNOVIAL FLUID based on water-soluble polymer, characterized in that, to improve lubricity, it further comprises a mesogenic esters of cholesterol, sodium carboxymethyl cellulose and gemodez in the following ratio, wt.

Mesogenic esters of cholesterol 0,2-1,0

Of sodium carboxymethyl cellulose 0,8-1,2

Gemodez Else

2. Fluid under item 1, characterized in that as mesogenic esters of cholesterol use a mixture of acetate cholesterol, pelargonate cholesterol, cholesterol oleate in a weight ratio of respectively 10 30 60.

 

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