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GB2121067A - Polymerizable composition for temporary substitution of bone tissue defects - Google Patents

Polymerizable composition for temporary substitution of bone tissue defects Download PDF

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Publication number
GB2121067A
GB2121067A GB08215993A GB8215993A GB2121067A GB 2121067 A GB2121067 A GB 2121067A GB 08215993 A GB08215993 A GB 08215993A GB 8215993 A GB8215993 A GB 8215993A GB 2121067 A GB2121067 A GB 2121067A
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GB
United Kingdom
Prior art keywords
composition
bone
composition according
calcium
bone tissue
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Granted
Application number
GB08215993A
Other versions
GB2121067B (en
Inventor
Alla Yakovlevna Akimova
Anatoly Borisovich Davydov
Galina Mikhailovna Derkach
Valeria Iosifovna Timokhina
Sergei Stepanovich Tkachenko
Vladimir Vladimirovich Rutsky
Mstislav Vasilievich Volkov
Irina Sergeevna Shepeleva
Alexandr Vasilievich Shiryaev
Semen Ilich Lipkin
Vladimir Mikhailov Musyanovich
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Vnii Ispytatel Med Tech
Original Assignee
Vnii Ispytatel Med Tech
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
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Publication date
Application filed by Vnii Ispytatel Med Tech filed Critical Vnii Ispytatel Med Tech
Priority to GB08215993A priority Critical patent/GB2121067B/en
Publication of GB2121067A publication Critical patent/GB2121067A/en
Application granted granted Critical
Publication of GB2121067B publication Critical patent/GB2121067B/en
Expired legal-status Critical Current

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    • CCHEMISTRY; METALLURGY
    • C08ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08KUse of inorganic or non-macromolecular organic substances as compounding ingredients
    • C08K5/00Use of organic ingredients
    • C08K5/04Oxygen-containing compounds
    • C08K5/09Carboxylic acids; Metal salts thereof; Anhydrides thereof
    • C08K5/098Metal salts of carboxylic acids
    • CCHEMISTRY; METALLURGY
    • C08ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08FMACROMOLECULAR COMPOUNDS OBTAINED BY REACTIONS ONLY INVOLVING CARBON-TO-CARBON UNSATURATED BONDS
    • C08F22/00Homopolymers and copolymers of compounds having one or more unsaturated aliphatic radicals each having only one carbon-to-carbon double bond, and at least one being terminated by a carboxyl radical and containing at least one other carboxyl radical in the molecule; Salts, anhydrides, esters, amides, imides or nitriles thereof
    • C08F22/30Nitriles
    • C08F22/32Alpha-cyano-acrylic acid; Esters thereof
    • CCHEMISTRY; METALLURGY
    • C08ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08KUse of inorganic or non-macromolecular organic substances as compounding ingredients
    • C08K3/00Use of inorganic substances as compounding ingredients
    • C08K3/10Metal compounds
    • C08K3/105Compounds containing metals of Groups 1 to 3 or of Groups 11 to 13 of the Periodic Table

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  • Chemical & Material Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Medicinal Chemistry (AREA)
  • Polymers & Plastics (AREA)
  • Organic Chemistry (AREA)
  • Materials For Medical Uses (AREA)

Abstract

A composition for temporary substitution of bone tissue comprises (a) ???-cyanoacrylic acid esters and (b) certain powder-like fillers, in the following proportions of the components, per cent by weight of the total of (a) and (b):- (a) ???-cyanoacrylic acid esters 60-40 (b) calcium salt of organic or inorganic acid with a particle size of from 0.01 to 0.5 mm 40-60. The composition optionally includes regeneration stimulants and antiseptics and is useful in fixation of bone fragments, fixation of bone homo-transplantant in the case of anterior cervical spondyolodesis, temporary filling of bone cavities and the like treatments.

Description

SPECIFICATION Composition for temporary substitution of bone tissue defects The present invention relates to medicine and, more specifically, to a composition for a temporary substitution of bone tissue defects. The composition is useful both individually or in combination with an ultrasonic treatment for the fixation of bone fragments, fixation of bone homotransplantant at anterior cervical spondylosis, temporary filling of bone cavities, recovery of articular surfaces, fixation of on-bone implanted active electrodes for a subsequent electrostimulation of osteogenesis and the like.
The composition for a temporary substitution of bone tissue defects on the basis of a cyanacryiic acid esters and a filler, according to the present invention, contains a powder-like filler-a salt of calcium of an organic or inorganic acid with a particle size of from 0.01 to 0.5 mm, the components being present in the following proportions, per cent by weight: a-cyanacrylic acid esters 60 to 40 calcium salt of organic or inorganic acid with a particle size of 0.01-0.5 mm 40 to 60.
As calcium salts of organic or inorganic acids the composition according to the present invention can incorporate calcium carbonate, calcium gluconate, calcium chloride, calcium phosphate, calcium citrate. It is preferably that the composition would contain calcium gluconate or calcium carbonate. The impart a predetermined physiological effect to the preparation, it should be added with regeneration stimulants and anti-septics.
The preparation according to the present invention preferably contains, as a regeneration stimulant, 4-uracylcarboxylic acid (orotic acid) or its derivatives in an amount of from 10 to 30% by weight.
As the antiseptic the composition according to the present invention preferably incorporates 1 ,4-di-N-oxy 2, 3-dihydroxymethylquinoxaline or 1,4-di-N-oxy 2, 3-diacetoxymethylquinoxaline in an amount of from 10 to 30% by weight.
As the composition base intended for the provision of adjusted time limits of biodestruction of the cured conglomerate, it is preferred to use a mixture of ethyl-ci-cyanacrylate and ethoxyethyla-cyanacrylate, the components being present in the following proportions, per cent by weight: ethyl-ci-cyanacrylate 80 to 95 ethoxyethyl-ci-cyanacrylate 20 to 5.
The composition is prepared directly before use by mixing the composition components at room temperature in a polyethylene or fluoroplastic vessel. After mixing of the components a paste-like mass is formed which has adherence to the bone tissue. The life time of the composition ranges within 5 to 30 minutes depending on the employed calcium salt and proportions of the components.
The paste-like mass is applied onto a preliminarily dried surface of the bone tissue. To accelerate the process of curing of the composition use can be made of an ultrasonic treatment (amplitude 50-55 ym, frequency 26.5 kHz, treatment time 30-60 seconds).
Curing of the composition by the effect of ultra sound occurs within 1-2 minutes, without ultrasonic treatment-within 5 to 30 minutes. The use of calcium salt in the composition according to the present invention as a filler makes it possible to produce a uniform mixture after blending of the components which, in turn, ensures reproducible data as regards the speed of biodestruction of the cured conglomerate.
The use of the composition containing a calcium'salt and a mixture of ethyl- and ethoxyethyl ci-cyanacrylate makes it possible to reduce the duration of biodestruction of the cured conglomerate by 0.8-2 times as compared with the composition incorporating bone chips and ethyl-a-cyanacrylate.
To increase hydrophilic power of the composition, particles of the salt of calcium can be coated with envelopes of a non-toxic polymer soluble in water and insoluble in ci-cyanacrylates.
As the salts of calcium use can be made of different organic and inorganic calcium salts such as calcium carbonate, calcium chloride, calcium phosphate, calcium citrate, calcium gluconate and the like.
As the regeneration stimulants use is made of 4-uracylcarboxylic acid, potassium salt of 4uracycarboxylic acid and the like. As antiseptics use can be made of antibiotics or such compounds as l,Q-di-N-oxide 1 ,4-di-N-oxide 2,3-dihydroxymethylquinoxaline, 1,4-di-N-oxy 2,3-diacetoxyme- thylquinoxaline. The regeneration stimulants and antiseptics are introduced in an amount ranging from 10 to 30% by weight.
The composition according to the present invention has no toxic effect, ensures a lasting evolution of the regeneration stimulants into the trauma zone, retains bactericidal properties with 2-3 weeks after the operation and provides no hindering effect on regeneration of the bone tissue.
The composition for a temporary substitution of bone tissue defects has been tested in clinics on 200 patients. The composition is prepared right before use and applied onto preliminarily dried surface of a bone tissue. The composition has thus been tested.
For filling of bone cavities in radical operations on patients suffering from chronical osteomyelitis including shoulder osteomyelitis, femoral osteomyelitis, tibial osteomyelitis, ishiatic osteomyelitis. In all cases there is observed healing of wounds by primary extension; no complications associated with the use of the composition according to the present invention are observed.
The use of the composition according to the present invention makes it possible to avoid drainage.
In reconstruction operations of wrongly consolidated fractures, rheumatic polyarthritis, for fixation of bone fragments of forearm, peroneal bone, shinbone, collar bone, fixation of bone transplantants with the use of the composition of this invention healing occured without complications. In none of the cases any secondary displacement was observed.
In fixation of bone grafts to prevent micro- and macro-shiftings in reconstruction steps of osteoplastic operations of chronical otitis media, non-purulent disease of middle ear, chronical diseases of nasal accessory sinuses, maxillary sinus cyst, ethmoidal sinus osteoma with the use of the composition according to the present invention no complications were observed. The use of the composition made it possible to reduce the duration of stay of the patients in the hospital by 4-6 days, as well as to ensure a strict restoration of anatomic reliefs which is especially important from both functional and cosmetic standpoint. The composition according to the present invention has been also tested for fixation of on-bone implanted electrodes for carrying out electrostimulation, as well as for fixation of bone homotransplantant at anterior cervical spondyoledosis.
The use of the composition according to the present invention has made it possible to avoid an external fixation of the cervical part of spinal column thus allowing an early activization of patients. The duration of stay of the patients in hospital was reduced by 2 weeks. No shiftings and complications due to the use of the composition were observed.
For a better understanding of the present invention some specific examples illustrating the composition for a temporary substitution of defects of bone tissue are given hereinbelow.
Example 1 A composition for a temporary substitution of bone tissue defects consists of the following components, per cent by weight: calcium carbonate with a particle size of from 0.01 to 0.05 mm 50 ethyl-a-cyanacrylate 45 ethoxyethyl-cu-cyanacrylate 5 A sterile weighed portion encapsulated in dextrane, mixed with ci-cyanacrylic acid esters till the formation of a paste-like mass. The cohesion strength of the cured conglomerate determined on the instrument Dinstat Dis (ultimate bending strength) is 200 to 250 kg/cm2. The sample weight decrease after residence in water at the temperature of 37"C for 28 days is 8%. The composition is intended for fixation of bone fragments, bone transplantant, securing of on-bone implanted active electrodes.
Example 2 A composition for a temporary substitution of bone tissue defects consists of the following components, per cent by weight: calcium gluconate with a particle size of from 0.05 to 0.2 mm 60 ethyl-ci-cyanacrylate 32 ethoxyethyl-ci-cyanacrylate 8.
A sterile weighed portion of calcium gluconate is mixed with ci-cyanacrylic acid esters to obtain a paste-like mass. The cohesion strength of the cured conglomerate determined on the instrument Dinstat Dis (ultimate bending strength) is 230-250 kg/cm2. The sample weight decrease after residence in water at the temperature of 37"C for 28 days is 20%. The composition is intended for fixation of bone fragments, bone transplantants, securing of on-bone implanted active electrodes, restoration of articular surfaces.
Example 3 A composition for a temporary substitution of bone tissue defects consists of the following components, per cent by weight: disubstituted calcium orthophosphate 60 ethyl-ci-cyanacrylate 40.
The composition is prepared following the procedure similar to that described in Example 1 hereinbefore. The cohesion strength as determined on the instrument Dinstat Dis (ultimate bending strength) is 250-280 kg/cm2. The sample weight decrease after residence in water at the temperature of 37"C for 28 days is 5%. The composition is intended for fixation of on-bone implanted active electrodes, restoration of articular surfaces.
Example 4 A composition for a temporary substitution of bone tissue defects consists of the following components, per cent by weight: calcium gluconate 20 potassium salt of 4-uracylcarboxylic acid 20 ethyl-ci-cyanacrylate 40 ethoxyethyl-cu-cyanacrylate 10.
The composition is prepared in a manner similar to that described in Examples 1 and 2. The cohesion strength of the cured conglomerate determined on the instrument Dinstat-Dis is 200 to 220 kg/cm2. The sample weight decrease after residence in water for 28 days at the temperature of 37"C is 20"C. The composition is intended for fixation of electrodes, restoration of articular surfaces, fixation of bone homotransplantants in the case of anterior servical spondyoledosis.
Example 5 A composition for a temporary substitution of bone tissue defects consists of the following components, per cent by weight: calcium carbonate 30 1 ,4-di-N-oxy 2,3-diacetoxymethylquinoxaline 10 ethyl-ci-cyanacrylate 60.
The composition is prepared in a manner similar to that of Examples 1 and 2. The cohesion strength of the cured conglomerate as determined on the instrument Dinstat-Dis (ultimate bending strength) is 250-280 kg/cm2. The sample weight decrease after residence in water at the temperature of 37"C for 28 days is 15%. The composition is intended for fixation of bone transplantants, filling of post-operation bone cavities with a volume of up to 2 cm3.
Example 6 A composition for a temporary substitution of bone tissue defects consists of the following components, per cent by weight: calcium gluconate 30 4-uracylcarboxylic acid 8 kanamycin (antibiotic produced by Actinomyces kanamyceticus) 12 ethyl-ci-cyanacrylate 40 ethoxyethyl-a-cyanacrylate 10.
The composition is prepared in a manner similar to that of Examples 1 and 2. The cohesion strength of the cured conglomerate determined on the instrument Dinstat-Dis (ultimate bending strength) is 200-200 kg/cm2. The sample weight decrease after residence in water at the temperature of 37 C for 28 days is 23%.
The composition is intended for filling post-operation bone cavities, fixation of bone fragments.
Example 7 A composition for a temporary substitution of bone tissue defects consists of the following components, per cent by weight: calcium gluconate 30 1 ,4-di-N-oxy 2,3-dihydroxymethylquinoxaline 12 4-uracylcarboxylic acid 8 ethyl-a-cyanacrylate 48 ethoxyethyl-a-cyanacrylate 2.
The composition is prepared in a manner similar to that described in Examples 1 and 2. The cohesion strength of the cured conglomerate as determined on the instrument Dinstat Dis (ultimate bending strength) is 200 to 230 kg/cm2. The sample weight decrease after residence in water at the temperature of 37"C for 28 days is 25%.
The composition is intended for fixation of bone homo-transplantants, filling of post-operation bone cavities in radical operations on patients suffering form chronical osteomyelitis and the like. The use of the composition in reconstruction stages of osteoplastic operations in otolaryngology has enabled a shortened duration of stay of the patients in the hospital by 4-6 days.
Example 8 (comparative) A composition for a temporary substitution of bone tissue defects consists of the following components, per cent by weight: modified bone chips 50 ethyl-ci-cyanacrylate 50.
The cohesion strength of the composition determined on the instrument Dinstat-Dis (ultimate bending strength) is varied within the range of from 100 to 300 kg/cm2. The sample weight loss after residence in water at the temperature of 37"C for 28 days varies from 2 to 15% (at the constant proportions of the components).

Claims (9)

1. A composition for temporary substitution of bone tissue comprising one or more esters of a-cyanoacrylic acid and a filler which is at least one calcium salt of an organic or inorganic acid and which has a particle size of from 0.01 to 0.5 mm, the proportions of the components, in per cent by weight, being ci-cyanoacrylic acid esters: 60 to 40 calcium salt of an organic or inorganic acid with a particle size of 0.01-0.5 mm: 40 to 60
2. A composition according to Claim 1, wherein the calcium salt is calcium gluconate or calcium carbonate.
3. A composition according to Claim 1 or 2, wherein a regeneration stimulant is included in an amount of 10 to 30 wt.%.
4. A composition according to Claim 3, wherein the regeneration stimulant is 4-uracylcarboxylic acid or a derivative thereof.
5. A composition according to any of Claims 1 to 4, wherein an antiseptic is included in an amount of 10 to 30% by weight.
6. A composition according to Claim 5, wherein the antiseptic is 1,4-di-N-oxy-2,3-dihydroxy methylquinoxaline or 1 ,4-di-N-oxy-2, 3-diacetoxymethylquinoxaline.
7. A composition according to any of Claims 1 to 6, wherein the a-cyanoacrylic acid ester is a mixture of ethyl-ci-cyanoacrylate with ethoxyethyl-ci-cyanoacrylate.
8. A composition according to the foregoing Claims 1 to 7, substantially as described in the Specification and Examples set forth hereinbefore.
9. A composition comprising one or more esters of a-cyanoacrylic acid and a calcium salt filler, the composition being for use in a method of surgery or therapy practised on the human or animal body.
GB08215993A 1982-06-01 1982-06-01 Polymerizable composition for temporary substitution of bone tissue defects Expired GB2121067B (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
GB08215993A GB2121067B (en) 1982-06-01 1982-06-01 Polymerizable composition for temporary substitution of bone tissue defects

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
GB08215993A GB2121067B (en) 1982-06-01 1982-06-01 Polymerizable composition for temporary substitution of bone tissue defects

Publications (2)

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GB2121067A true GB2121067A (en) 1983-12-14
GB2121067B GB2121067B (en) 1986-06-11

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Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB2212488B (en) * 1986-06-09 1991-01-30 Coors Biomedical Co Biocompatible particles and cloth-like article made therefrom
WO1992001741A1 (en) * 1990-07-24 1992-02-06 Epron Industries Limited Degradable plastics material
DE10212348A1 (en) * 2002-03-14 2003-09-25 Aesculap Ag & Co Kg Curable composition based on a component curable at body temperature and a reabsorbed component obtained by catalytic polymerization useful for bone cementation

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB1343790A (en) * 1970-06-11 1974-01-16 Johnson & Johnson Adhesive composition
GB1419640A (en) * 1972-01-03 1975-12-31 Lee Pharmaceuticals Dental adhesive composites

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB1343790A (en) * 1970-06-11 1974-01-16 Johnson & Johnson Adhesive composition
GB1419640A (en) * 1972-01-03 1975-12-31 Lee Pharmaceuticals Dental adhesive composites

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB2212488B (en) * 1986-06-09 1991-01-30 Coors Biomedical Co Biocompatible particles and cloth-like article made therefrom
WO1992001741A1 (en) * 1990-07-24 1992-02-06 Epron Industries Limited Degradable plastics material
DE10212348A1 (en) * 2002-03-14 2003-09-25 Aesculap Ag & Co Kg Curable composition based on a component curable at body temperature and a reabsorbed component obtained by catalytic polymerization useful for bone cementation

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Publication number Publication date
GB2121067B (en) 1986-06-11

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PCNP Patent ceased through non-payment of renewal fee

Effective date: 19930601