Method for regeneration of bony tissue in experiment

FIELD: experimental medicine.

SUBSTANCE: on should introduce solution into fracture area at the following ratio of ingredients, g/l: 1-hydroxyethylidenediphosphonic acid 1.80 - 2.06, water-free calcium chloride 1.44 - 2.22, gadolinium (III) nitrate hexahydrate 0.30 - 0.40, dysprosium (III) chloride hexahydrate 0.038 - 0.076, moreover, solution's pH corresponds to 7.3 - 7.8. The present innovation enables to shorten the process of bony tissue regeneration in the site of its lesion or defect and, also, shorten the period for restoring normal physiological function of traumatized bone.

EFFECT: higher efficiency of regeneration.

22 ex, 1 tbl

 

The invention relates to the field of treatment of various bone injuries, particularly fractures and cracks, and can be implemented in medical and veterinary surgery.

There is a method of regeneration of bone tissue in the experiment by fixing plaster cast with Windows in it at the level of fracture for installation of electrodes, applying a bandage soaked in a solution of calcium chloride, the flannel strip and impact on the place of fracture of the weak (~ 5 mA) electric current for 15 min, carried out for the entire period of treatment 12-20 times [1]. The disadvantage of this technical solution is a very long process of regeneration of bone tissue.

There is also known a method of regeneration of bone tissue in the experiment, in which before applying plaster bandages into the fracture area, introduce a solution containing 1-hydroxyethylidenediphosphonic acid, calcium chloride, nitrate gadolinium (III) and water [2]. This method on a set of attributes and the achieved technical effect is the closest to the claimed us the object and therefore can be selected as a prototype. The disadvantage of this known method is also relatively long process of regeneration of bone tissue.

The aim of the present invention is an additional reduction of the duration of the process of regeneration of bone is Kani at her place of damage or defect, and time restore the normal physiological functions of the injured bone.

The declared objective is achieved by the fact that in the known method [2] regeneration of bone tissue, in which before applying plaster bandages into the fracture area, introduce a solution containing 1-hydroxyethylidenediphosphonic acid, calcium chloride, nitrate gadolinium (III) and water in this solution is further added chloride dysprosium (III) in the following ratio of ingredients, g/l:

1-Hydroxyethylidenediphosphonic acid 1,80-to 2.06;

Calcium chloride 1,44-2,22;

Nitrate gadolinium (III) the uranyl 0,30-0,40;

Chloride, dysprosium (III) pentahydrate 0,038-0,076;

pH of 7.3-7.8 for.

In use of the present invention, the process of regeneration of bone tissue is much faster and the time to restore the normal physiological functions of the injured bone can be reduced compared with that for the prototype method [2] by 30-40%.

Previously in the literature not documented solution for the regeneration of bone tissue, which is the qualitative and quantitative composition would coincide with the solution used in the inventive us the object. Said gives us grounds to assert that the claimed object corresponds to the first criterial feature of the invention specified in the Patent Law of the Russian Federation, is a novelty. Comparison of the known is marketed features of the prototype method [2] and characteristics make changes, namely the use in the composition of the solution for injection, mentioned in [2], chloride dysprosium (III), it is not possible to predict that we observe in the experiment a significant reduction in the duration of recovery of normal physiological functions of the injured bone in the place of damage or defect compared with those for the known method [2]. This allows us to conclude that the claimed technical solution is not obvious from the well-known in the art and consequently, it has the second criterion characteristic of the invention under the Patent Law of the Russian Federation, namely an inventive step. Finally, we state our method does not require any special equipment and can easily be implemented even in an outpatient setting. In this regard, we may say that we declare our object and satisfies the third criterion characteristic of the invention under the above Law and industrial applicability.

Declare on the subject of the invention, the method of regeneration of bone tissue can be illustrated by the following examples.

Example 1

(preparation of the proposed solution)

In a volumetric flask of 1000 ml is injected above substances: 1-hydroxyethylidenediphosphonic acid, calcium chloride anhydrous nitrate gadolinium (III) and uranyl chloride, dysprosium (III), the uranyl - in amounts corresponding to the above concentrations. Then diluted to approximately 950 ml distilled water. After that, the resulting mixture was added a concentrated solution of alkali (e.g., 10% aqueous sodium hydroxide solution) to achieve the necessary medium acidity (pH of 7.3-7.8)to. In conclusion, the resulting composition was adjusted with distilled water to a volume of 1000 ml. of the resulting solution can be immediately used for the implementation of the proposed method; if necessary, it can be a long time (not less than 1 year) is stored in a closed vessel without losing the claimed properties.

Example 2

Prepare a solution with a pH of 7.5 the following composition:

1 - Hydroxyethylidenediphosphonic acid 1,80 g/l;

Calcium chloride anhydrous 1.44 g/l;

Nitrate gadolinium (III) the uranyl 0,30 g/l;

Chloride, dysprosium (III), the uranyl 0,038 g/l

Thus prepared solution is injected under anesthesia domestic cat Nordic breed, which artificially made fracture tibia hind legs, 1 hour later after causing her injury, in the amount of 2.0 ml for 2 min in place of damaged bones. After injection of the fracture site of the bone conclude fixed in a plaster cast, in which the injured limb segments can stand up to restore musculoskeletal is uncle. The process of regeneration of the injured bone tissue is controlled by the radiographic method (in some cases used radiolucent synthetic bandage CELLACAST Xtra firm Lohmaim&Rausher, in other cases, for radiography of the plaster cast was cut open at the site of injury).

Some characteristics of the process of regeneration of damaged bone tissue in this specific case is presented in table 1.

Example 3

Perform as example 2, but for injection use solution in the amount of 2.0 ml with a pH of 7.8 following composition:

1-Hydroxyethylidenediphosphonic acid 1,90 g/l;

Calcium chloride anhydrous 1.70 g/l;

Nitrate gadolinium (III) the uranyl 0.35 g/l;

Chloride, dysprosium (III), the uranyl 0,038 g/l

Example 4

Perform as example 2, but for injection use solution in the amount of 2.0 ml with pH 7.8 of the following composition:

1-Hydroxyethylidenediphosphonic of 2.06 g/l;

Calcium chloride anhydrous 2.20 g/l;

Nitrate gadolinium (III) the uranyl 0.40 g/l;

Chloride, dysprosium (III), the uranyl 0,038 g/l

Example 5 (similar to [1])

Perform as example 2, but the solution indicated there composition in place of damage to the bone before applying fixed plaster bandages do not enter, and in a cast cut out "window" at the level designated trauma to the bone for the electrodes to the skin of the animal in place damages the Oia put a piece of bandage, soaked in 5% aqueous solution of calcium chloride, then the flannel strip and the active "+" electrode on the opposite surface is indifferent electrode ("-") gasket, moistened with water, then attach the electrodes to the electroplating apparatus "Thread-1" and ignore the current 5 mA for 15 minutes, the procedure Described above (the so-called "electrophoresis") during the period of regeneration of bone tissue is periodically repeated (the number of such sessions for the entire course of treatment - up to 20). Some characteristics of the process of regeneration of damaged bone tissue for this case are also presented in table 1.

Example 6 (prototype [2])

Perform as example 2, but for injection use solution in the amount of 2.0 ml with a pH of 7.8 following composition:

1-Hydroxyethylidenediphosphonic acid 2,00 g/l;

Calcium chloride anhydrous 1.78 g/l;

Nitrate gadolinium (III) the uranyl 0.40 g/HP

Characteristics of the process of regeneration of damaged bone tissue, in this case Tauke presented in table 1.

Example 7

Prepare a solution of the composition indicated in example 2, and then enter it under anesthesia dog - mongrel (undetermined species), which artificially cause fracture of humerus, right front paw with significant displacement, after 6 hours after application to her injuries. The drug is administered in the amount of 2.5 ml / min is of 2 min, then travmirovannomu the sign in plaster shell. The process of bone regeneration control radiographic method.

Some characteristics of the process of regeneration of damaged bone tissue for this case are shown in table 1.

Example 8

Perform actions using the General scheme of example 7, but for injection use solution, the composition of which is specified in example 3, in the amount of 2.5 ml

Example 9

Carried out as example 7, but for injection use solution, the composition of which is given in example 4, in the amount of 2.5 ml

Example 10 (similar to [1])

Perform under the scheme of example 5, but for fracture treatment, the nature of which is specified in example 7.

Example 11 (prototype [2])

Perform under the scheme of example 6, but for fracture treatment, the nature of which is specified in example 7.

Example 12 (comparative)

Perform, using the General scheme of example 7, but for injection use solution with a pH of 8.3 of the following composition:

1-Hydroxyethylidenediphosphonic acid 1.50 g/l;

Calcium chloride anhydrous 1.28 g/l;

Nitrate gadolinium (III) the uranyl 0,50;

Chloride, dysprosium (III), the uranyl 0,020 g/l

Example 13 (comparative)

Done using the same scheme as in example 7, but for injection use a solution with a pH of 7.1 of the following composition:

1-Hydroxyethylidenediphosphonic acid 2,31 g/l;

X is arid anhydrous calcium 2.50 g/l;

Nitrate gadolinium (III) the uranyl 0,59 g/l;

Chloride, dysprosium (III), the uranyl 0,116 g/l

Example 14 (comparative)

Act the same way as in example 12, but the pH of the solution equal to 7.1.

Example 15 (comparative)

Carried out analogously to example 13, but the pH of the solution is equal to 8.2.

Example 16

Prepare a solution of the composition shown in example 3, and then put him under anesthesia dog (breed - Scottish shepherd, collie), which was brought to the clinic with a natural way to the trauma (diagnosis: closed fracture of humerus, right front paw with a significant offset) after 12 hours after injury. The above solution is injected after the reposition of bone fragments in the amount of 2.5 ml for 2 min and then enter into the damaged area of bone in a fixed plaster shell. The process of bone regeneration control radiographic method.

Some characteristics of the process of regeneration of bone tissue for this case are also presented in table 1.

Example 17

Prepare a solution of the composition indicated in example 3, and then put him under anesthesia dog (breed - Airedale), which was hit by a car and taken to the hospital with a diagnosis of closed fracture of both femurs" later, 2 days after injury, in the amount of 2×2.5 ml for 2 min, in compliance is either damaged areas of both legs. Then the damaged area is enclosed in a plaster cast. The process of bone regeneration control radiographic method. Some characteristics of the process of regeneration of bone tissue for the specified cases are presented in table 1.

Example 18

Prepare a solution of the composition indicated in example 2, and then enter it anesthetized rabbit, which artificially cause deliberate injury of both femur by drilling under General anesthesia with an electric drill with a drill diameter 5 mm, While the introduction of the above solution in the amount of 1.0 ml (time - 2 min) is carried out in travmirovannomu only one of the injured bone (the other left as a control). After that all the injured place conclude fixed in a plaster cast. Control over the process of regeneration of bone tissue perform radiographic method.

Some characteristics of the process of regeneration of bone tissue for this case are shown in table 1.

Example 19

Carried out as described in example 18 the scheme, but for injection use solution, the composition of which is specified in example 3, in the amount of 1.0 ml.

Example 20

Perform as example 18, but for injection solution using the composition indicated in example 4, in the amount of 1.0 ml.

Example 21 (compare the AUX)

Perform according to the General scheme of example 18, but for injection use solution, the composition of which is specified in example 12, in the amount of 1.0 ml.

Example 22 (comparative)

Spend as example 18, but for injection use solution, the composition of which is given in example 13, in the amount of 1.0 ml.

Example 23 (similar to [1])

Carried out as example 16, but the solution indicated there into the injury site of any of injured bones, not impose, but act as in example 5. Some characteristics of the process of regeneration of bone tissue for the marked case is given in table 1.

Example 22 (prototype [2])

Prepare the solution as in example 6, but for the treatment of bone damage, the nature of which is specified in example 18.

Some characteristics of the process of regeneration of bone tissue for the marked case is also shown in table 1.

From the data in table 1 clearly shows that the use of the claimed our method compared with the method of the prototype [2] are quite significantly (30-40%) to reduce the duration of the process of regeneration of bone tissue at the site of injury, and this phenomenon is observed regardless of the type subjected to injury of animals. At the same time, it should be noted that declare to us the number of chloride dysprosium (III), which is used in this process is, are significant and the reduction in its quantity below the proposed limit and higher above the top of the proposed limit, accompanied by an increase in the duration of the process of regeneration of bone tissue. Note also that we conducted to measure the strength of the regenerated using methods [1, 2] and using the claimed us the way of regeneration of bone tissues showed no appreciable differences between them. II finally, we state our solution, according to the clinical picture of blood regeneration of the injured bone tissue, as well as the observations of the subjective condition of injured animals in the course of their treatment (appetite, reactivity and the like), does not have any pronounced toxicity; in addition, each of the members of this solution ingredients, according to [3-4], also not is a toxic compound.

LITERATURE

1. Special physical therapy /edited Lnikolova. Sofia, 1983. 350 S.

2. RF patent № 2061402. Method of regeneration of bone tissue in the experiment / Devyatov F. W., Kholmogorov E.A., Latypov A.L. //Inventions No. 16 (10.06.96).

3. Harmful chemicals. Inorganic compounds I-IV groups /edited Wahiawa. L.: Chemistry, 1988. S, 248-263.

4. Dyatlova NM, Temkina VA, K.I. Popov Chelating agents and metal complexons. M.: Chemistry 1988. S-501.

Table 1
# exampleTravmirovannomu animalThe period of full recovery of locomotor function of the injured bone segment, the day
2Cat (North European breeds)6
3Cat (North European breeds)6
4Cat (North European breeds)6
5 (analog)Cat (North European breeds)51
6 (prototype)Cat (North European breeds)9
7Dog (unspecified species)10
8Dog (unspecified species)9
9Dog (unspecified species)11
10 (similar)Dog (unspecified species)60
11 (prototype)Dog (unspecified species)15
12 (compare.)Dog (unspecified species)20
13 (compare.)Dog (unspecified species) 16
14 (compare.)Dog (unspecified species)18
15 (compare.)Dog (unspecified species)21
16Dog (Scottish shepherd)11
17Dog (Airedale)10
18Rabbit5(18)
19Rabbit6(18)
20Rabbit5(18)
21 (compare.)Rabbit5(18)
22 (compare.)Rabbit6(18)
23 (similar)Rabbit15(18)
24 (prototype)Rabbit9(16)
Note: Figures in brackets are for examples 18-24 represent relevant characteristics of the process of regeneration of the injured bone, who had not before plaster fixation injection of the proposed solution.

Method of regeneration of bone tissue in the experiment by fixing the fragments of plaster bandage, followed by the introduction into the fracture area of a solution containing 1 - hydroxyethylidenediphosphonic acid, calcium chloride, nitrate gadolinium (III) and water, characterized in that h is o with the aim of reducing the duration of the process of regeneration of bone tissue at the site of damage or defect, and the recovery time of the normal physiological functions of the injured bone, the solution is further added chloride dysprosium (III) in the following ratio of ingredients, g/l:

1-Hydroxyethylidenediphosphonic acid of 1.80-2.06 to

Calcium chloride anhydrous 1,44-2,22

Nitrate gadolinium (III) the uranyl 0,30-0,40

Chloride, dysprosium (III), the uranyl 0,038-0,076

pH 7.3 to 7.8



 

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