KR100435419B1 - Bone-filling composition for stimulating bone-forming and bone-consolidation comprising calcium sulfate and viscous biopolymers - Google Patents

Abstract

The present invention relates to a composition for bone filling, containing calcium sulfate and a viscous polymer, which promotes early bone formation and bone hardening.

Description

Bone-filling composition for stimulating bone-forming and bone-consolidation comprising calcium sulfate and viscous biopolymers}

The present invention relates to a composition for bone filling, containing calcium sulfate and a viscous polymer, which promotes early bone formation and bone hardening.

Recently, bone defects often occur due to an automobile accident or disease, and accordingly, a need for supplementing a bone defect portion is emerging. In order to compensate for bone defects, bone grafts may be used, but bone fillers have recently been used a lot. Moreover, in recent years, a lot of bone anesthesia is performed to correct the legs and the dwarf jaw to increase the height, and accordingly, the demand for bone filler is further increased.

Osteogenesis is the induction of bone length growth by stretching, which is based on the principle of 'tension forces stimulate histogenesis'. It is designed for bone extension, but recently, it has been widely used for jaw bone extension. Jaw bone reconstruction is one of the recent developments of craniofacial surgery. By attaching a bone elongation device to the receded jawbone and the midfoot retreat, the bones of the face are gradually moved without performing extensive osteotomy. This treatment can improve the ratio of the face.

Bone debridement has been used successfully to correct bone defects in long bones since Ilizarov identified biomechanical factors for bone debridement (Ilizarov GA,J. Dis. Orthop. Inst., 48 (1): 1, 1988; Ilizarov GA,Clin. Ortho.,239: 263, 1989; Ilizarov GA,Clin. Ortho., 238: 249, 1989). To achieve successful bone distraction, it is necessary to preserve blood circulation in the bone distraction and to stabilize the external fixator on both sides of the osteotomy of the cortical bone to promote bone hardening by gradually extending the length of bone (White SH,J. Bone Join Surgery, 72-B: 350, 1990; White SH,Orthop. Clin. North. Amer., 22: 569, 1991; Fishgrund J., Paley D., Sulter D.,Clin. Orthop, 301: 31, 1994).

The duration of bone hardening depends on the site of the distracting bone (facial bone or iliac bone), the hematogenous condition, and the age of the patient.The bone hardening period after bone distraction is 3 to 5 weeks for children and 6 weeks for adults. It takes 12 to 12 weeks, and in the long bone it takes about 3 to 6 months regardless of age. Therefore, when bone reconstruction is performed on the craniofacial bone, the treatment period takes 2 months to 4 months, including latent, bone retardant, and osteosclerosis. Thus, the long bone hardening period increases the possibility of complications such as pin infection. Problems that may or may not delay the return to everyday life have been raised.

In a post-distraction bone study to shorten the duration of treatment, Charls and Sailer reported that stretching 1 mm per day showed stronger biochemical and physiological properties than stretching 2-3 mm (Carls & Sailer, 1999). J. Craniomaxillofac Surg ., 94: 152, 1994). Ilizarov also notes that stretching to 1 mm per day yields the best results because stretching to 0.5 mm per day causes immature osteosclerosis and stretching to 2 mm per day causes undesirable changes to the stretched tissue. Ilizarov, J. Dis. Orthop . Inst., 48 (1): 1, 1988; Ilizarov, Clin. Ortho 239: 263, 1989. In addition, continuous stretching is known to cause least tissue damage and most capillary neovascularization and bone formation. Therefore, if it is possible to shorten the period of bone distraction and bone hardening, it is expected that the possibility of complications due to the long period of bone hardening can be prevented and the overall treatment period can be shortened to return the patient to daily life early. Therefore, in order to shorten the bone distraction period and bone hardening period, the filler is used to promote bone formation and promote bone hardening.

On the other hand, autologous bone grafts, treated allografts or xenografts and bone graft substitutes are known to stimulate bone formation. Autologous bone grafts are used to fill bone cavities or bone defects to eliminate voids and injuries from infections, tumors and surgery, or to repair joint unions or nonunion fractures. When anger is made, osteoprogenitor cells differentiate into boney osteogenesis cells, and the activity of these osteogenic cells causes new bone regeneration and bone defect healing. However, autologous bone is limited in the amount that can be collected and the secondary morbidity is added to the donor site has a high morbidity (morbidity). Therefore, bone morphogenic protein or other bone graft substitutes are used to induce bone regeneration in stretched areas. Among them, bone morphogenic protein is considered to be the most powerful osteoinductive substance, but it is very expensive and difficult to obtain. Due to its disadvantages, there are many limitations in clinical use.

Calcium sulfate is a bone filler that is biocompatible and induces blood vessel growth and osteoblast growth and early hardens bone. The substance induces new bone formation in a suitable environment to provide a normal bone structure, prevents the growth of undesirable connective tissue, acts as a shield for bone healing, and is replaced by bone during healing. Beeson injected calcium sulfate into the frontal sinus of dogs and found that bone regeneration was enhanced within 4-6 months (Beeson W., Arch Otolaryngol , 107: 664, 1981). Pecora et al. The effect of partial or full bone healing was reported after 3 weeks at the site of bone defect in the mandible of the mandible (Pecora G., Andreana S., Margarone III JE., Covani U., Sottosanti JS., Oral Surg. Oral Med. Oral Pathol.Oral Radio Endod., 84: 434, 1997). Pelter reported that calcium sulfate could be safely used in patients with various bone defects, absorbed into the body within weeks or months, resulting in bone regeneration, and its use in infected cavities did not pose a risk or complication (Pelter LF). , Am. J. Surg ., 97 (3): 311, 1959). However, since calcium sulfate is in the form of tablets or powders, it is difficult to inject into bone loss sites, and further surgical trauma is inevitable to inject, which requires surgery once more and leaves scars on the patient.

Accordingly, the present inventors have made efforts to improve the method of administering calcium sulfate, and as a result, a gel-like composition containing calcium sulfate and a viscous polymer can be easily administered to the bone deletion site by injection, The present invention has been found to shorten the period of bone hardening by promoting bone formation and promoting bone hardening, which is present only at the site of bone deletion without spreading to an organ.

SUMMARY OF THE INVENTION An object of the present invention is to provide a gel-like bone filling composition which is easy to administer to a bone defect site and which, after administration, remains for a long time at the bone defect site to promote bone formation and bone hardening.

1 is a photograph of calcium sulfate salt pills used in the preparation of the composition of the present invention,

2 is a photograph showing that the external fixing device to the experimental animal during bone distraction using the composition of the present invention

FIG 3 A is a scanning only the carboxymethyl cellulose in the present invention radiographs showing the extent of cure after bone surgery by 3 weeks after bone distraction in 10 days the distraction control group 1 by 1 ㎜ day,

B is a radiograph showing the degree of bone stiffness after 6 weeks after bone distraction in the control group 1 injected only carboxymethyl cellulose and stretched for 10 days at 1 mm per day in the present invention,

C is a radiograph showing the degree of bone hardening after 3 weeks after bone distraction in the control group 2 injected with only carboxymethyl cellulose in the present invention and stretched for 5 days at 2 mm per day,

D is a radiograph showing the degree of bone hardening after 6 weeks after bone distraction in the control group 2 injected only carboxymethyl cellulose in the present invention and stretched for 5 days at 2 mm per day,

Figure 4 A is a radiograph showing the degree of bone hardening after 3 weeks after the injection of the composition from the group of calcium sulfate salt injected with the composition of the present invention and stretched for 1 day 10 mm 1 day,

B is a radiograph showing the degree of bone hardening after 6 weeks after injecting the composition from the group of calcium sulfate salt in which the composition of the present invention is injected and stretched for 10 days at 1 mm per day for 10 days,

5ofAIs It is a radiograph showing the degree of bone stiffness after 3 weeks after the injection of the composition from the calcium sulfate salt group 2, which is injected for 2 days and stretched for 5 days at 2 mm per day,

B is a radiograph showing the degree of bone hardening after 6 weeks after injecting the composition from the two groups of calcium sulfate salt infused with a composition of the present invention and stretched for 5 days at 2 mm per day for 5 days,

FIG 6 A is a photograph of the histological section of after three weeks postoperative bone distraction elapsed in the present invention carboxymethyl cellulose only 10 days injection, and by day 1 ㎜ the distraction control group 1 in,

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B is a photograph showing the histological cross-section after 6 weeks after bone distraction in the control group 1 injected only carboxymethyl cellulose in the present invention and stretched for 1 day 10 mm by 1 mm per day,

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C was confirmed by hematoxylin & eosin staining in which the new bone is formed at the edge of the control group 1 of the bone angioplasty, which was injected with carboxymethylcellulose only and stretched for 1 day at 1 mm per day in the present invention. Organization picture,

A; Osteoblasts, B; Fibrous tissue

7A is a photograph showing the histological cross-section after 3 weeks after bone distraction in the control group 2, which is injected with carboxymethyl cellulose in the present invention, and stretched carboxymethyl cellulose for 5 days at 2 mm per day for 5 days.

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B is a photograph showing a histological cross-section after 6 weeks after bone distraction in the control group 2, which was injected with Sumann in the present invention and stretched for 2 days at 2 mm per day for 5 days,

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C is a tissue photograph confirmed by hematoxylin & eosin staining that the new bone is formed at the edge of the control group 2 bone distraction site injected only carboxymethyl cellulose in the present invention and stretched for 5 days 2 mm per day,

A; Osteoblasts, B; Fibrous tissue

A FIG. 8 is a photograph showing the histological section of a back bone distraction alcohol 3 weeks after 10 days from the distraction calcium sulfate salt group 1 composition is by injection and day 1 ㎜ of the present invention,

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B is the area of the distraction by staining the histological cross-section of A with hematoxylin eosin and the middle filled with photographs to show that osteoblasts and fibrous tissue,

A; Osteoblasts, B: fibrotic tissue

C is a photograph showing a histological cross-section after 6 weeks of bone distraction in a group of calcium sulfate salts in which the composition of the present invention is injected and stretched for 10 days at 1 mm per day for 10 days,

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D is a picture showing the formation of new bone throughout the stretched area by staining the histological section of C with hematoxylin & eosin,

9A is a photograph showing a histological cross-section after 3 weeks of bone distraction in a group of calcium sulfate salts injected with the composition of the present invention and stretched for 2 days by 2 mm for 5 days,

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B is a photo showing the histological section of A stained with hematoxylin & eosin, and the stretched area is connected to the fibrous band and osteoblast formation occurs at the edge.

C is a photograph showing the histological cross-section after 6 weeks of bone distraction in the group of calcium sulfate salts in which the composition of the present invention is injected and stretched for 5 days at 2 mm per day for 5 days,

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D is a photograph showing the formation of new bone in about half of the stretched area by staining the histological section of C with hematoxylin & eosin.

A; Osteoblasts, B; Fibrous tissue

In order to achieve the above object, the present invention provides a gel-like bone filling composition containing a calcium sulfate and a viscous polymer.

The present invention also provides a use of the composition for promoting bone formation and bone hardening.

Hereinafter, the present invention will be described in detail.

The present invention provides a gel-like bone filling composition containing calcium sulfate and a viscous polymer.

The composition of the present invention,

a) 20-80% by weight of a mixture consisting of 90-99% by weight CaSO ₄ and 1-10% by weight of CaCO ₃ , MgCO ₃ and CaCO ₃ .MgCO ₃ ; And

b) 80 to 20% of a viscous polymer.

The composition of the present invention may further include one or more inorganic salts selected from the group consisting of CaCO ₃ , MgCO ₃ , CaCO ₃ · MgCO ₃ and mixtures thereof based on CaSO ₄ . According to an embodiment of the present invention is preferably composed of 90~99% CaSO ₄ and _{CaCO 3, MgCO 3, CaCO 3} · MgCO 3 1~10% by weight by weight based on the total weight of inorganic salt, CaSO ₄ 98 ~ 99 wt. yi%, CaCO ₃ 0.3 ~ 1 a composition containing a weight%, MgCO ₃ 0.3 ~ 1% by weight and CaCO ₃ · MgCO ₃ 0.5~1% by weight is more preferred. Calcium sulfate is an inexpensive bone filler and is usually supplied in the form of powder or pills in a highly purified state (see FIG. 1 ). The greatest advantage of the calcium sulfate is the absorption rate in parallel to the growth of new bone, when the new bone is restored to the anatomy and structural characteristics when the calcium sulfate is absorbed. In addition, the calcium sulfate is a relatively safe material having excellent absorbency and does not exhibit an inflammatory reaction.

In the present invention, a gel-type composition in which powdered calcium sulfate and a viscous polymer were mixed was used and prepared. Viscosity polymers are carboxymethylcellulose, hyaluronic acid, chitosan, polyacrylic acids, polyvinyl ehters, polystyrenes, cellulose ethers. ), Cellulose esters, starches and polysaccharides. In the present invention, a case where carboxymethyl cellulose is used as a polymer having viscosity as a preferred embodiment is illustrated.

In the composition in which the powdered calcium sulfate and the viscous polymer are mixed, the ratio of the calcium sulfate and the viscous polymer is preferably 20:80 to 80:20, more preferably 50:50.

As a preferred embodiment for the preparation of the composition of the gel form of the present invention as a carboxymethyl cellulose used as a viscous polymer may be used a sodium salt of polycarboxymethyl ether of cellulose. The carboxymethylcellulose sodium salt is an odorless, hygroscopic powder exhibiting various colors such as white, cream color, used as a base material, and used as a suspending agent or emulsion.

Carboxymethylcellulose is also known to be harmless to the human body, such as conventionally used as a protective agent during ileostomy or colostomy (Raynolds JEF., Martindale., The Extra Pharmacopoeia., 29: 1433, 1989).

The present inventors injected a mixture of calcium sulfate and a viscous polymer into the stretched area using an 18-gauge needle, which is simple and easy to inject calcium sulfate and does not require time-consuming secondary surgery. Because you can avoid surgical scars. The composition of the present invention promoted new bone formation with vigorous mineralization three weeks after injection and showed extensive new bone formation after six weeks. In addition, the composition was slowly absorbed after being injected into the bone distracted site, leaving only calcium sulfate, no effect on bone regeneration, and no inflammatory response.

The present invention also provides a use of the composition for promoting bone formation and bone hardening.

The present inventors investigated the effect of the composition on early bone hardening during bone distraction in the mandibular canine in order to determine whether the composition for bone filling of the present invention can be used for such use.

As a result, in the radiographs taken at 3 and 6 weeks, calcification progressed over time in the mandibular distraction area in all groups except the control group (control group 2) 2 mm per day. There was a radiolucent zone between the stretched mandibular fragments and abutmented bilateral mandibular fragments with different cured zones in each group. At 3 weeks after bone distraction, radiodense zones were hardly observed in the control group and the composition 2 group stretched 2 mm per day, but a significant amount was observed in the group 1 stretched 1 mm per day. At week 6, there was a gradual linkage of the radiopaque area to the center of the distracted area in the control group 1 and the composition 1 and 2 groups, with the composition 1 group showing the most radiopaque findings. was not observed (see Figs. 3 to 5).

As a result of the histological examination, the control group 1 showed osteoblasts, which partially form osteoids at the edges of the distracted site at 3 weeks, and many fibrotic tissues at the center (see FIG. 6A ) . More new bone was observed in the stretched area than at 3 weeks, but the center was filled with fibrotic tissue ( see FIGS. 6B and 6C ). In control group 2, new bone was observed only in a portion of the distracted area and was almost filled with fibrotic tissue (see FIG. 7 ).

On the other hand, in the composition 1 group, many active osteoblasts were observed at the edge and the center of the distracted site at 3 weeks and filled with new bone and fibrotic tissue (see FIGS . 8A and 8B ). At 6 weeks, new bone formed throughout the distracted area was distributed similarly to normal cortical bone (see FIGS . 8C and 8D ). In the composition 2 group, the stretched site was connected to the fibrous band at 3 weeks, and bone formation was observed at the edge (see FIGS . 9A and 9B ). At 6 weeks, new bone was formed at about half of the distracted site (see FIGS . 9C and 9D ).

As confirmed above, 2 mm stretched composition 2 groups per day had less bone formation than 1 mm stretched composition 1 group, and clinically, 1 mm stretch per day is considered useful. The results are in line with previous studies on elongation rates in which clinically faster elongation rates shorten the overall duration of treatment.

In the control group 1, the distracted area was not completely replaced by the new bone until 6 weeks after distraction, and most of the distracted area was the central fibrosis and the marginal ossification. Thus, as a result of the above and conventional Califano and Komuro (Califano L, Cortese A, Zupi A, Tajana G, J. Oral Maxillofac. Surg. , 1994 , 52, 1179; Komuro Y, Takato T, Harii K, Yonemara Y, Plast.Reconstr . Surg. , 1994 , 94, 152) The duration of bone hardening is preferably at least 6 weeks, and the faster the rate of distraction, the shorter the time required for bone extension. Since the pain and complications of the patient can be reduced, the faster the speed is, the better it is, unless it interferes with bone formation.

In general, stretched bone tends to be slightly absorbed and usually 10-20% overextension is recommended. However, there is no accurate data on the degree of hyperextension and the degree of hyperextension is determined by the operator's experience. It is thought that the absorption of these stretched bones depends on the degree of mineralization of the stretched bones, and it is recommended to wait 6 to 10 weeks after bone distraction in adults according to the patient's age. However, in the present invention, because the composition promotes bone regeneration more than the control group, it was determined that overextension is not necessary.

From the above results, it was confirmed that the composition of the present invention can be useful as a very economical and biocompatible composition for bone filling since it promotes new bone formation and bone hardening at an early stage and shortens the bone hardening period.

Hereinafter, the present invention will be described in detail by way of examples.

However, the following examples are merely to illustrate the invention, but the content of the present invention is not limited to the following examples.

Example 1 Preparation of a Bone Filling Composition

The present inventors prepared a composition for bone filling in which carboxymethyl cellulose and calcium sulfate salt were mixed. Specifically, 98.9 g of CaSO ₄ H ₂ O, 0.3 g of CaCO ₃ , 0.3 g of MgCO ₃ and 0.5 g of CaCO ₃ · MgCO ₃ were mixed well, and then added to 100 g of carboxymethylcellulose to suspend well. The gel-like composition of the invention was prepared.

<Example 2-Example 7>

To the composition on the gel was prepared in the same manner as in Example 1 by a composition ratio shown in Table 1.

Composition ratio of the composition CaSO ₄ H ₂ O CaCO ₃ MgCO ₃ CaCO ₃ · MgCO ₃ Ratio with CMC Example 2 98 g 0.5 g 0.5 g 1 g 20:80 Example 3 98 g 0.4 g 0.4 g 1.2 g 30:70 Example 4 98.5 g 0.3 g 0.2 g 1 g 40:60 Example 5 98.5 g 0.5 g 0.5 g 0.5 g 60:40 Example 6 99 g 0.3 g 0.2 g 0.5 g 70:30 Example 7 99 g 0.2 g 0.5 g 0.3 g 80:20

Experimental Example 1 Osteotomy

The present inventors observed changes by injecting the composition of the present invention after bone osteotomy in the dog's mandible in order to determine whether the composition of the present invention promotes new bone formation and osteosclerosis early during bone distraction. .

Specifically, eight dogs 5 months old were used as experimental animals, four of which were divided into control groups and the other four were grouped into composition groups, and these control and composition groups were further stretched by 1 mm per day. It was subdivided into the control 1 group, the composition 1 group, and the stretch group (control 2 group, the composition 2 group) by 2 mm.

The dogs maintained breathing by endotracheal intubation after general anesthesia, and the surgical site was shaved and basic disinfection and application were performed. A 3-4 ㎝ skin incision was made along the lower end of the mandible, the masseter muscle was held to expose the outer surface of the mandible. The mandibular bone was completely cut by performing an osteotomy perpendicular to the mandibular body with a chainsaw. The pins to be fixed to the external fixation device were fixed to the bone fragments 1 cm from the left and right sides of the osteotomy site. At this time, the pin was pushed into the mandible so as to penetrate firmly. After fixing the two pins were mounted on the bone extension device (MolinaDistractors, Wells Johnson Company) ( Fig. 2 ).

The incision site was sutured with 5-0 vicryl and 5-0 nylon sutures and the experimental animals were recovered from anesthesia. Penicillin antibiotics (100,000 μg / kg) were intramuscularly injected every 12 hours for 7 days after surgery, and 10 ㏄ analgesics were administered orally every 6 hours for pain relief. A soft diet was given from the second day immediately after surgery to the regular diet from the third day. From the 5th day after surgery, the control group 1 and the composition 1 group were stretched for 10 days to 1 mm per day, totaling 10 mm, and the control group 2 and the composition 2 group were 2 mm per day, totaling 10 mm for 5 days. Distracted.

At the end of bone distraction, 1 ml of bone filling composition of the present invention prepared in Example 1 was injected into the bone distracted portion through an 18-gauge needle ( FIG. 1B ). In the control group, only carboxymethylcellulose was injected into the 1 ml bone distraction site.

The bone distraction device was maintained for 6 weeks after the infusion of the composition for bone hardening and bone regeneration. Each group of 4 animals was pentobarbital at 3 weeks after the end of bone distraction and 4 weeks after the end of bone distraction. ) Was sacrificed by injection of an overdose (40-50 mg / kg).

<1-1> radiography

The experimental animals of each group who underwent bone distraction were weekly radiographed, and bone formation and bone stiffness were observed on the basis of radiographs obtained at 3 and 6 weeks.

As a result, as shown in Figs. 3 to 5, in the radiographs taken at 3 and 6 weeks, calcification progressed over time in the mandibular distraction region in all groups except the control 2 group ( Fig. 3 to Fig . 3) . 5 ). There were radiographic zones between the stretched mandibular fragments, and bilateral mandibular fragments adjacent to each other. At 3 weeks after bone distraction, radiodense zone was hardly observed in the control group and the composition 2 group, but a considerable amount was observed in the composition 1 group. At week 6, there was a gradual linkage of the radiopaque area to the center of the distracted area in the control group 1 and the composition 1 and 2 groups, with the composition 1 group showing the most radiopaque findings. Not observed.

<1-2> Histological examination

In the above, bone specimens were collected from the distal mandibular region and the normal bone tissue around the bone using a chainsaw for histological examination of the experimental animal that had been completed bone osteotomy. The collected bone fragments were fixed in 10% neutral formalin for 1 week and then decalcified in 10% nitric acid and 10% sodium citrate for 2 days, followed by dehydration and paraffin fixation according to a conventional method. A specimen of −6 μm was prepared and stained with hematoxylin-eosin to observe histological findings under an optical microscope.

As a result, in the control group 1, osteoblasts, which partially form osteoids at the edges of the distracted site at 3 weeks, and many fibrotic tissues were observed at the center ( FIG. 6a ). New bone was observed more than 3 weeks, but the center was filled with fibrotic tissue ( Figs. 6b and 6c ). In control group 2, new bone was only observed in a portion of the distracted area and was mostly filled with fibrotic tissue ( FIG. 7 ). On the other hand, in the composition 1 group, many active osteoblasts were observed at the edge and the center of the distracted site at 3 weeks and were filled with new bone and fibrotic tissue ( FIGS. 8A and 8B ). At 6 weeks, new bone formed throughout the distracted area was distributed similarly to normal cortical bone ( FIGS. 8C and 8D ). In the composition 2 group, stretched sites were connected to the fibrous band at 3 weeks, and bone formation was observed at the edges ( FIGS. 9A and 9B ), and at 6 weeks, new bone was formed at about half of the stretched sites ( FIG. 9c and FIG. 9d ).

As described above, the gel-like composition of the present invention induces new bone formation, provides normal bone structure, prevents the growth of undesirable connective tissues, serves as a protective film when healing bones, and replaces them with bones during the healing process. Therefore, it can be usefully used as a composition for bone filling, which is suitable for living body and induces blood vessel growth, osteogenic cells, and bone hardening.

Claims (6)

1) 20-80% by weight of a mixture consisting of 90-99% by weight of CaSO ₄ and 1-10% by weight of CaCO ₃ , MgCO ₃ and CaCO ₃ .MgCO ₃ ; And 2) A composition for promoting bone formation and bone hardening, characterized in that consisting of 80 to 20% of the polymer having a viscosity. The method according to claim 1, characterized in that the bone formation and bone hardening, characterized in that 98% to 99% by weight of CaSO ₄ , 0.3 to 1% by weight of CaCO _3, 0.3 to 1% by weight of MgCO _{3 and} 0.5 to 1% by weight of CaCO ₃ · MgCO ₃ Promotional composition. The method of claim 1, wherein the polymer having viscosity is carboxymethylcellulose, hyaluronic acid, chitosan, polyacrylic acids, polyvinyl ehters, polystyrenes, cellulose. A composition for promoting bone formation and bone hardening, characterized in that selected from the group consisting of ether (cellulose ethers), cellulose esters (cellulose esters), starches and polysaccharides (polysaccharides). The composition for promoting bone formation and bone hardening according to claim 3, wherein the polymer having viscosity is carboxymethylcellulose. The composition of claim 1 wherein the ratio of calcium sulfate to the viscous polymer is 50:50. The composition of claim 1 wherein the composition is gelled.