CA1211713A - Paste for haemostasis and temporary bridging of defects in cases of bone trauma - Google Patents

Paste for haemostasis and temporary bridging of defects in cases of bone trauma

Info

Publication number
CA1211713A
CA1211713A CA000446593A CA446593A CA1211713A CA 1211713 A CA1211713 A CA 1211713A CA 000446593 A CA000446593 A CA 000446593A CA 446593 A CA446593 A CA 446593A CA 1211713 A CA1211713 A CA 1211713A
Authority
CA
Canada
Prior art keywords
paste
bone
defects
haemostasis
cases
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.)
Expired
Application number
CA000446593A
Other languages
French (fr)
Inventor
Hermann Dahlke
Hans Muxfeldt
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.)
Ethicon Inc
Original Assignee
Ethicon Inc
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.)
Filing date
Publication date
Application filed by Ethicon Inc filed Critical Ethicon Inc
Application granted granted Critical
Publication of CA1211713A publication Critical patent/CA1211713A/en
Expired legal-status Critical Current

Links

Classifications

    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L27/00Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/02Inorganic materials
    • A61L27/12Phosphorus-containing materials, e.g. apatite
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00Medicinal preparations containing peptides
    • A61K38/16Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • A61K38/168Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from plants
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L27/00Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/40Composite materials, i.e. containing one material dispersed in a matrix of the same or different material
    • A61L27/44Composite materials, i.e. containing one material dispersed in a matrix of the same or different material having a macromolecular matrix
    • A61L27/46Composite materials, i.e. containing one material dispersed in a matrix of the same or different material having a macromolecular matrix with phosphorus-containing inorganic fillers
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61FFILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
    • A61F2310/00Prostheses classified in A61F2/28 or A61F2/30 - A61F2/44 being constructed from or coated with a particular material
    • A61F2310/00005The prosthesis being constructed from a particular material
    • A61F2310/00179Ceramics or ceramic-like structures
    • A61F2310/00293Ceramics or ceramic-like structures containing a phosphorus-containing compound, e.g. apatite
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L2400/00Materials characterised by their function or physical properties
    • A61L2400/04Materials for stopping bleeding
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L2430/00Materials or treatment for tissue regeneration
    • A61L2430/02Materials or treatment for tissue regeneration for reconstruction of bones; weight-bearing implants

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Animal Behavior & Ethology (AREA)
  • Engineering & Computer Science (AREA)
  • Epidemiology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Dermatology (AREA)
  • Oral & Maxillofacial Surgery (AREA)
  • Transplantation (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Inorganic Chemistry (AREA)
  • Organic Chemistry (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Botany (AREA)
  • Composite Materials (AREA)
  • Materials Engineering (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Immunology (AREA)
  • Materials For Medical Uses (AREA)
  • Dental Preparations (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicines Containing Plant Substances (AREA)
  • Medicinal Preparation (AREA)
  • Noodles (AREA)

Abstract

Abstract of the Disclosure A paste for haemostasis in cases of bone trauma, containing a prolamin, such as zein and tricalcium phosphate or hydroxyl apatite in finely dispersed form and a physiologically compatible diluent, such as aqueous ethanol. The paste is applied on the traumatized bone. The paste also may serve for temporary bridg-ing of defects in bones.

Description

L2~ 3 The invention relates to a paste for haemostasis and temporary bridging of defects in cases of bone trauma.

Since 1892 the bone wax first described by Horsley and later on modified in various ways has been used as a means of mechanically stopping the bleeding of bones. Its original composition was 7 parts of bees wax, 1 part of almond oil, and 1 part of almond oil, and 1 part of salicyclic acid. The bone wax most frequently used today consists of 89 parts of bees wax and 11 parts of isopropyl palmitate. This preparation causes strong foreign-substance reactions and chronic inflammation reactions. A minor portion only is re-sorbed within 12 weeks, while at the same time the osteo-anagenesis is delayed considerably. From the clinical point of view, the possible formation of pseudo arthroses must be watched.
.
It is the ob~ect of the invention to provide a paste for haemostasis and temporary bridging of defects in cases of bone trauma, which paste will safely stop bleeding of the traumatized bone and not impede the osteogenesis but rather act osteoinductively. The solution of the problem posed is on the surprising finding that a paste containing 8 prolamin and finely dis-persed tricalcium phosphate or hydroxyl apatite and a physiologically com-patible diluent provides optimum haemostasis of the traumatized bone and is an excellent means for the temporary bridging of defects.

In accordance with the present teachings, a paste is provided for haemo-stasis and temporary bridging of defects in cases of bone trauma character-ized in that it contains from 3 to 60% by weight of prolamin and from 5 to 20% of tricalcium phosphate or hydroxyl apatite in finely dispersed form and a physiologically compatible diluent.

The diluent used preferably is a mixture of an aliphatic alcohol having from 2 to 5 carbon atoms, particularly ethanol and water at a volumetric ratio of approximately 1:1 to 10:0.5.

Prolamins are the major protein constituents of cereal grains or meal.
Contrary to all other proteins they can be extracted from flour by the use of 80% alcohol, yet they are not soluble in anhydrous alcohol or water. The most important prolamins are zein, gliadin, and hordein.
Zein is preferred in accordance with the invention. The prolamin, preferably zein is used in ,_~

23L~713 the paste in a quantity of from about 3 to 60, preferably 5 to 45% by weight.

Contrary to all other proteins, the prolamins are soluble in diluted alcohols and other solvents, but are not soluble in water. A mixture of ethanol and water is the preferred solvent and diluent, the water content ranging between 4 and 50%, depend-ing on how quickly the prolamin is desired to precipitate. In ethanol prolamins yield viscous, slightly thixotropic solutions.
The viscosity of the solutions rises as the concentration of ethanol rises, at the same prolamin content. On the other hand, the viscosity increases as the concPntration of prolamin in-creases, at a given concentration of ethanol.

The prolamins are resorbable so pseudoarthrosis cannot develop which is conceivable as a consequence of bone wax not being re-sorbed or being resorbed too slowly, e.g. in case of sternum closure.

The contents of finely dispersed hydroxyl apatite or tricalcium phosphate promote the regeneration of the bone. The particle size of the hydroxyl apatite or tricalcium phosphate in general lies within a range of from approximately 3 to 20 ~m, particu-larly from approximately 10 to 15 ~m.

The addition of methyl cellulose or carboxymethyl cell~lose in an amount of from 2 to 10% by weight provides optimum consisten-cy of the paste, thus yielding a preparation to stop bleeding of the bone when applied easily as a thin film. Also greater bone defects ca~ be filled and bridged by applying the paste.
Furthermore, it is possible to repair comminuted fractures.

An antibiotic may be added to the paste for use in prophylaxis and therapy of infections. Specific examples of useful anti-biotics are tobramycin, gentamycin, cefotaxim, and mixtures thereof. The antibiotic is used in suffici~ntly great quantity to obtain the complete inhibition of growth of the germs to be killed.

Instead of or in addition to the antibiotic the paste may con-tain a cytostatic drug. Specific examples of cytostatic sub-stances are mitomycin, dichlorene, decarbacin, or cisplatin.

~2~ 3 The cytostatic drug is used in an amount sufficient to retard the growth of the tumor.

Upon addition of fine fibers of resorbable polymer in an amount of from 1 to 15% by weight the consistency is changed such that the mass becomes kneadable and moldable so that it may be applied as a temporary bridging means of defects on bones~

Poly-~lactide-co-glycolide) is an hydrolyzable aliphatic poly-ester used to produce resorbable surgical suture material. Other resorbable fibrous polymers which may be incorporated in the paste according to the invention are polyglycolide, polylactide, polyoxalate, polysuccinate, polydioxanone, and poly-(esteramides).

The paste may be prepared in a way as disclosed in US patent 4,268,495 from which injectable solutions containing prolamin are known for embolization and occlusion.

It is easy to press the kneadable paste into bone defects and mold it so as to adapt it to the desired shape The mass solidi-fies within a period of from about 30 to 90 minutes.

The paste may be sterilized by gamma radiation, heat, or the addition of propylene oxide in an amount of from about 0.25 to 0.5% by weight.

The examples will explain the invention.
Example 1 A paste is prepared from the following components:
ethanol 60% V/V 51.7 g zein 19.4 g methyl cellulose 5.0 g tricalcium phosphate (particle size about 10~m~ 15.0 g propylene oxide 1.0 g The zein is introduced into the 60% aqueous ethanol, while care-fully stirring the mass. Upon complete dissolution (about 12 to 14 hours) pH adjustment is made to approximately 6.5 to 6.8, with the aid of a physiologically compatible acid or base . The ethyl cellulose and tricalcium phosphate then are introduced into the viscous solution obtained. The resulting paste finally is mixed in the cold with 1 g of propylene oxide and immediately bottled. An additional 1 to 13 g of fine fibers of a resorbable polymer, preferably polyglycolide or polylactide may be incorporated in the paste.

Example 2 In accordance with example 1 a paste is prepared from the com-ponents below:
ethanol 60% V~V 51.7 g zein 19.4 g carboxymethyl cellulose - 5.0 g hydroxyl apatite (particle size about 10 ~m) 20.0 g propylene oxide 1.0 g Upon longitudinal separation of the sternum of a dop the paste prepared in accordance with examples 1 and 2 is applied on the spongy part of the bone to stop the bleeding. The paste is applicable well and smoothly penetrates into the tiny cavities of the bone. Diffuse bleeding out of the bone is stopped at once.

Upon obduction after 28 days the partial bridging of the former defect can be observed. Histological proof of the haemostatic substance is no longer possible.

Example 3 In accordance with example l a paste is prepared from the components listed below:
ethanol 60% V/V 51.7 g zein 19.4 g methyl cellulose 5.0 g tricalcium phosphate (particle size about 10 ~m) 15.0 g tobramycin 0.7 g propylene oxide 1.0 g The paste according to the invention is used to fill an infect-ed bone cavity. Bone cavities in the ehronically infected bone marrow are a locus minoris resistentiae for recurring infections.

12~7~3 Upon cleaning of the bone marrow space up to sound tissue the paste is used to stop the bleeding which begins. At the same time the cavity either is filled completely or lined along the walls, depending on ~he size. The precipitation which initiates at once stops the paste from flowing out.

In a bacteriological test the bone pieces withdrawn periodically in the experiment demonstrated distinct inhibition of germ growth heyond the 28th day, and then at a declining tendency.

Example 4 In accordance with example 1 a paste is prepared from the fol-lowing components:
ethanol 60~ V/V 51.7 g zein 19O4 g carboxymethyl cellulose 5.0 g hydroxyl apatite (particle size about 10 ~m) 20.0 g mitomycin 0.8 g propylene oxide 1.0 g The paste according to the invention is used to retard the growth of malignant tumoxs of the bone or bone marrow which certainly or perhaps are existing. In context with the cytostatic drug mitomycin the paste either may be applied in a flowable consi-stency or in the form of the finest solid particles upon preci-pitation or evaporation of the solvent.

The flowable form wil~ be chosen if it is desired that the paste stop heavy bleeding from the area of tumor. Again a bone tumor may be treated which either is known and considered inoperable or which has been operated on and requires measures to stop the bleeding. The prophylactic introduction of a cytostatic drug to the border of the excision is of great advantage because in this way it can be guaranteed that the effectiveness of the cy-tostatic substance will last long enough. The range of the ef-fectiveness is to be assumed to reach about 1 cm away from the paste. As a systemic effect here is given under certain condi-tions only, the release of the cytostatic drug may be very high.
In fact it still amounts to several gamma up to a distance of

Claims (5)

C L A I M S
1. A paste for haemostasis and temporary bridging of defects in cases of bone trauma, characterized in that it contains from 3 to 60% by weight of prolamin and from 5 to 20% of tricalcium phosphate or hydroxyl apatite in finely dispersed form and a physiologically compatible diluent.
2. The paste as claimed in claim 1, characterized in that the prolamin is aein and the diluent is a mixture of an aliphatic alcohol having from 2 to 5 carbon atoms and water.
3. The paste as claimed in claim 2, characterized in that the paste contains from 2 to 10% of methyl cellulose or carboxy methyl cellulose.
4. The paste as claimed in claims 1 to 3, characterized in that the paste in addition contains an antibiotic or a cytostatic agent.
5. The paste as claimed in one of claims 1 to 3, characterized in that it contains fine fibers of a resorbable polymer, preferably polyglycolide, polylactide, poly-(lactide-co-glycolide), polyoxalate, polysuccinate, polydioxanone, or poly-(esteramides).
CA000446593A 1983-02-03 1984-02-02 Paste for haemostasis and temporary bridging of defects in cases of bone trauma Expired CA1211713A (en)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
EP83101023.6 1983-02-03
EP83101023A EP0115549B1 (en) 1983-02-03 1983-02-03 Paste for hemostasis and for temporary relief of defects in the traumatism of bones

Publications (1)

Publication Number Publication Date
CA1211713A true CA1211713A (en) 1986-09-23

Family

ID=8190275

Family Applications (1)

Application Number Title Priority Date Filing Date
CA000446593A Expired CA1211713A (en) 1983-02-03 1984-02-02 Paste for haemostasis and temporary bridging of defects in cases of bone trauma

Country Status (9)

Country Link
EP (1) EP0115549B1 (en)
JP (1) JPS59148724A (en)
AT (1) ATE31025T1 (en)
AU (1) AU561584B2 (en)
CA (1) CA1211713A (en)
DE (1) DE3374659D1 (en)
ES (1) ES529425A0 (en)
IN (1) IN158149B (en)
ZA (1) ZA84805B (en)

Families Citing this family (10)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
NL8402534A (en) * 1984-08-17 1986-03-17 Gerrit Johannes Brinks MATERIAL, SUITABLE FOR USE AS AN IMPLANT MATERIAL IN HUMANS AND ANIMAL TO REPLACE ABSENT BONE TISSUE, AND METHOD FOR PREPARING THE MATERIAL.
JPH0755235B2 (en) * 1986-09-08 1995-06-14 新田ゼラチン株式会社 Injection material for bone formation
DE3825211A1 (en) * 1988-07-25 1990-02-01 Henkel Kgaa IMPROVED BODY RESORBONABLE WAXES (III)
FR2668367B1 (en) * 1990-10-26 1994-05-13 Centre Nal Recherc Scientifique IMPLANTABLE MEDICINE WITH PROLONGED EFFECT.
FR2715853B1 (en) * 1994-02-08 1996-04-26 Centre Nat Rech Scient Composition for bio-material; preparation process.
GB2316940A (en) * 1996-08-30 1998-03-11 Queen Mary & Westfield College Silicon-substituted hydroxyapatite
JP3114016B2 (en) * 1998-05-15 2000-12-04 株式会社ホギメディカル Wound hemostatic material having cell adhesion promoting effect
GB2466979A (en) * 2009-01-19 2010-07-21 Simon James Baker Porous ceramic compositions for use as haemostatic agents
DE102015014581A1 (en) 2015-11-12 2017-05-18 Nele Schmidt Prolamine-containing gels, process for their preparation and their use
CN113518804B (en) * 2019-01-08 2022-12-06 上海交通大学 Ink material for 3D printing, preparation method and application

Family Cites Families (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
FR2364644B1 (en) * 1976-09-20 1981-02-06 Inst Nat Sante Rech Med NEW BONE PROSTHESIS MATERIAL AND ITS APPLICATION
DE2657370C2 (en) * 1976-12-17 1982-11-11 Hans Dr.med. Dr.med.dent. 8000 München Scheicher Means for covering and / or filling in bone defects
GB1584080A (en) * 1977-12-05 1981-02-04 Ethicon Inc Absorbable hemostatic composition
DE2843963A1 (en) * 1978-10-09 1980-04-24 Merck Patent Gmbh BODY-RESORBABLE SHAPED MATERIAL BASED ON COLLAGEN AND THEIR USE IN MEDICINE
DE2803869C2 (en) * 1978-01-30 1983-12-29 Ethicon, Inc., 08876 Somerville, N.J. Injectable embolization and occlusion solution
US4268495A (en) * 1979-01-08 1981-05-19 Ethicon, Inc. Injectable embolization and occlusion solution
DE2917037C2 (en) * 1979-04-27 1980-12-11 Josef Dipl.-Chem. Dr. 8000 Muenchen Gaensheimer Parenterally medicinal, partially absorbable multi-component material based on polymeric substances

Also Published As

Publication number Publication date
AU2402584A (en) 1984-08-09
ES8507349A1 (en) 1985-09-01
ZA84805B (en) 1985-09-25
EP0115549A1 (en) 1984-08-15
JPS59148724A (en) 1984-08-25
ES529425A0 (en) 1985-09-01
JPH0359702B2 (en) 1991-09-11
DE3374659D1 (en) 1988-01-07
EP0115549B1 (en) 1987-11-25
IN158149B (en) 1986-09-13
ATE31025T1 (en) 1987-12-15
AU561584B2 (en) 1987-05-14

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