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US20010056069A1 - Use of collagen for the treatment of degenerative articular processes - Google Patents

Use of collagen for the treatment of degenerative articular processes Download PDF

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Publication number
US20010056069A1
US20010056069A1 US09/680,569 US68056900A US2001056069A1 US 20010056069 A1 US20010056069 A1 US 20010056069A1 US 68056900 A US68056900 A US 68056900A US 2001056069 A1 US2001056069 A1 US 2001056069A1
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United States
Prior art keywords
collagen
treatment
articular processes
skin
injection suspension
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Abandoned
Application number
US09/680,569
Inventor
Edwin Klaus
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Individual
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Individual
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Priority to US09/680,569 priority Critical patent/US20010056069A1/en
Publication of US20010056069A1 publication Critical patent/US20010056069A1/en
Abandoned legal-status Critical Current

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Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • A61K38/39—Connective tissue peptides, e.g. collagen, elastin, laminin, fibronectin, vitronectin, cold insoluble globulin [CIG]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00

Definitions

  • the invention relates to the use of collagen for the treatment of degenerative articular processes.
  • the basic type of degenerative, non-inflammatory joint diseases is arthropathy or Arthrosis deformans in old age. Squat-bodied human beings, more men than women, after the 50th year are mainly affected. The condition begins slowly, but also progresses intermittently and at the beginning without pain. The joints are only tender upon certain movements. Avoiding strain on the joints promotes the progression of the condition, but exercise and massages afford relief. Good successes can also be achieved by the treatment with ultra-short waves.
  • Reconstituted type II collagen can be used for the detection of antibodies against intact type II collagen in the blood in the case of arthrorheuinatism (JP-A 62-012 800).
  • Collagens are long-fibred, linear-colloid, highly molecular scleroproteins of the extracellular matrix, which are found in connective tissues (e.g. skin, cartilage, sinews, ligaments and blood vessels), in the protein-containing ground substance of the bone (ossein) and in dentin together with proteoglycans. With a share of 25 to 30% they are considered to be the quantitatively most frequent animal proteins.
  • the structural basic unit of collagen, the tropocollagen (MW approx. 300,000), consists of three polypeptide chains in the form of special left-wound helices which, in turn, are righthandedly twisted around one other according to the technique known in ropery (triple helix).
  • the tropocollagen molecule is a “rope” with a length of 280 nm and a diameter of 1.4 nm; the fibrils have a cross-section of 200 to 500 nm (see Römpps Chemielexikon, vol. 3, page 2297, 1990).
  • the collagens are not continuously renewed. Once they are formed, they do not participate in the metabolism any more and age due to regular increase in cross-linking due to the formation of hydrogen bridge bonds, ester bonds of amino acid residues with sugar residues and of isopeptide bonds between long-chain amino acid chains.
  • Modified collagen is used in medicine as a temporary skin replacement, as a replacement for cornea and vitreous humour of the eye, as a replacement for sinews, synovial sheaths, hollow organs and blood vessels, as a blood plasma substitute and in wound healing (EP-B 52288, JP-A-52-076 416).
  • Collagen sponge is i.a. used as a haematostatic.
  • Collagen containing drugs are used to improve dilatatable deformations of the skin as they occur in scars, in skin atrophy caused by various causes and in skin creases caused by age. These collagen-containing drugs are injected under the skin areas to be filled and, for this reason, contain, as a rule, a local anaesthetic.
  • This object is attained according to the invention by using collagen for producing a drug for the treatment of degenerative articular processes.
  • the used collagen is unsoluble collagen, which can e.g. be obtained from calf and bovine skin; however, collagen from bovine skin is preferred.
  • the collagen is preferably contained in an injection suspension, particularly preferred in an amount of about 20 to 50 mg/ml.
  • the injection suspension is applied by means of injection into the joints according to the invention in the case of degenerative articular diseases such as arthrosis or activated arthrosis.
  • a local anaesthetic such as bupivacaine or lidocaine is preferably contained.
  • Lidocaine is contained with particular preference.
  • the preferred amount of the contained local anaesthetic is 1 to 5 mg/ml.
  • the intraarticular use of collagen according to the invention in a drug has the advantage that it promotes the lubrication process which only takes place insufficiently in an arthrosis due to its properties, without attacking any substances, i.e without causing a damage.
  • Carrier substances e.g. agents for the protection of cartilage can be included in the collagen as a secondary element.
  • Examples of such agents for the protection of cartilage are the preparations Dona 200 (active substance: D-glucosamine) and Dona 22S (active substance: D-glucosamine sulfate) and the homoeopathic agents Zeel and Heel.
  • the homoeopathic agent has the following composition:
  • 2.2 ml contain: extract (1:10) from Cartilago suis 22 ng, extract (1:10) from Funiculus umbilicalis suis 22 ng, extract (1:10) from Embryo suis 22 ng, extract (1:10) from Placenta suis (hormone-free) 22 ng, Rhus toxicodendr. ⁇ 0.2 mg, arnica ⁇ 0.2 mg, Dulcamara ⁇ 0.22 ⁇ g, Symphytum ⁇ 22 ⁇ g, Sanguinaria ⁇ 33 ⁇ g, sulphur ⁇ 39.6 ⁇ g, Nacid 0.22 ng, coenzyme A 0.22 ng, ( ⁇ )-a-liponic acid, 0.22 ng, sodium oxalic acetat 0,22 ng. Moreover, the drug can still be slightly tinted, e.g. with compatible dyes.
  • compositions of the active substance combination in the injection suspension are indicated in the following examples.
  • 1 ml of injection suspension containing: 1. 20 mg of collagen from calf skin 2 mg bupivacaine; 2. 30 mg of collagen from bovine skin 2 mg of bupivacaine; 3. 35 mg of collagen from bovine skin 3 mg of lidocaine; 4. 40 mg of collagen from bovine skin 3 mg of lidocaine; 5. 50 mg of collagen from calf skin 3.5 mg of bupivacaine.
  • a young women, 32 years old, with therapy-resistant gonalgia was treated about 11 ⁇ 2 years ago with injections of 0.5 ml of the collagen-containing injection suspension according to example 3 intraarticularily into the joints on the one side and 1.0 ml on the other side; subsequently she was completely symptom-free. It was not necessary to repeat the treatment.
  • Intraarticular injections of 1 ml of the collagen-containing injection suspension according to example 3 brought about an approx. 70% improvement of the complaints according to the patient's statement in the case of a left-side severe gonarthrosis. Since about 2 years, the complaints have remained constant.

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • General Health & Medical Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Medicinal Chemistry (AREA)
  • Animal Behavior & Ethology (AREA)
  • Chemical & Material Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Immunology (AREA)
  • Epidemiology (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Biomedical Technology (AREA)
  • Zoology (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Organic Chemistry (AREA)
  • Pain & Pain Management (AREA)
  • Rheumatology (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicinal Preparation (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)

Abstract

The invention relates to the use of collagen for the production of a drug for the treatment of degenerative articular processes. An injection suspension is preferably produced, which contains collagen and possibly a local anaesthetic. This injection suspension is applied into the affected joints by means of an injection.

Description

  • The invention relates to the use of collagen for the treatment of degenerative articular processes. [0001]
  • The basic type of degenerative, non-inflammatory joint diseases is arthropathy or Arthrosis deformans in old age. Squat-bodied human beings, more men than women, after the 50th year are mainly affected. The condition begins slowly, but also progresses intermittently and at the beginning without pain. The joints are only tender upon certain movements. Avoiding strain on the joints promotes the progression of the condition, but exercise and massages afford relief. Good successes can also be achieved by the treatment with ultra-short waves. [0002]
  • Further therapies, which have been customary so far, are the systematic administration of non-steroidal antirheumatic agents and possibly intra-articular injections of agents for the protection of cartilage, homoeopathic agents, local anaesthetics or cortisone. However, these therapies have the disadvantage that the destruction of the joints occurring finally due to degenerative joint processes cannot be prevented, but only delayed, since the new formation of synovial fluids, such as mucopolysaccharides, cannot be stimulated, and no synovial fluid is introduced into the affected joint from the outside. [0003]
  • Reconstituted type II collagen can be used for the detection of antibodies against intact type II collagen in the blood in the case of arthrorheuinatism (JP-A 62-012 800). [0004]
  • Collagens are long-fibred, linear-colloid, highly molecular scleroproteins of the extracellular matrix, which are found in connective tissues (e.g. skin, cartilage, sinews, ligaments and blood vessels), in the protein-containing ground substance of the bone (ossein) and in dentin together with proteoglycans. With a share of 25 to 30% they are considered to be the quantitatively most frequent animal proteins. The structural basic unit of collagen, the tropocollagen (MW approx. 300,000), consists of three polypeptide chains in the form of special left-wound helices which, in turn, are righthandedly twisted around one other according to the technique known in ropery (triple helix). The tropocollagen molecule is a “rope” with a length of 280 nm and a diameter of 1.4 nm; the fibrils have a cross-section of 200 to 500 nm (see Römpps Chemielexikon, vol. 3, page 2297, 1990). [0005]
  • As opposed to most proteins of the animal body, the collagens are not continuously renewed. Once they are formed, they do not participate in the metabolism any more and age due to regular increase in cross-linking due to the formation of hydrogen bridge bonds, ester bonds of amino acid residues with sugar residues and of isopeptide bonds between long-chain amino acid chains. [0006]
  • Modified collagen is used in medicine as a temporary skin replacement, as a replacement for cornea and vitreous humour of the eye, as a replacement for sinews, synovial sheaths, hollow organs and blood vessels, as a blood plasma substitute and in wound healing (EP-B 52288, JP-A-52-076 416). Collagen sponge is i.a. used as a haematostatic. Collagen containing drugs are used to improve dilatatable deformations of the skin as they occur in scars, in skin atrophy caused by various causes and in skin creases caused by age. These collagen-containing drugs are injected under the skin areas to be filled and, for this reason, contain, as a rule, a local anaesthetic. [0007]
  • It is the object of the present invention to produce a drug for the therapy of degenerative articular processes which does not have the aforementioned disadvantages. [0008]
  • This object is attained according to the invention by using collagen for producing a drug for the treatment of degenerative articular processes. [0009]
  • The used collagen is unsoluble collagen, which can e.g. be obtained from calf and bovine skin; however, collagen from bovine skin is preferred. [0010]
  • The collagen is preferably contained in an injection suspension, particularly preferred in an amount of about 20 to 50 mg/ml. The injection suspension is applied by means of injection into the joints according to the invention in the case of degenerative articular diseases such as arthrosis or activated arthrosis. For this reason, a local anaesthetic such as bupivacaine or lidocaine is preferably contained. Lidocaine is contained with particular preference. The preferred amount of the contained local anaesthetic is 1 to 5 mg/ml. [0011]
  • As opposed to former therapies, the intraarticular use of collagen according to the invention in a drug has the advantage that it promotes the lubrication process which only takes place insufficiently in an arthrosis due to its properties, without attacking any substances, i.e without causing a damage. [0012]
  • “Carrier substances”, e.g. agents for the protection of cartilage can be included in the collagen as a secondary element. [0013]
  • Examples of such agents for the protection of cartilage are the preparations Dona 200 (active substance: D-glucosamine) and Dona 22S (active substance: D-glucosamine sulfate) and the homoeopathic agents Zeel and Heel. [0014]
  • The homoeopathic agent has the following composition: [0015]
  • 2.2 ml contain: extract (1:10) from [0016] Cartilago suis 22 ng, extract (1:10) from Funiculus umbilicalis suis 22 ng, extract (1:10) from Embryo suis 22 ng, extract (1:10) from Placenta suis (hormone-free) 22 ng, Rhus toxicodendr. φ 0.2 mg, arnica φ 0.2 mg, Dulcamara φ 0.22 μg, Symphytum φ 22 μg, Sanguinaria φ 33 μg, sulphur φ 39.6 μg, Nacid 0.22 ng, coenzyme A 0.22 ng, (±)-a-liponic acid, 0.22 ng, sodium oxalic acetat 0,22 ng. Moreover, the drug can still be slightly tinted, e.g. with compatible dyes.
  • The following examples explain the invention. [0017]
    • EXAMPLES 1 to 5
  • Various compositions of the active substance combination in the injection suspension are indicated in the following examples. [0018]
    1 ml of injection suspension containing:
    1.  20 mg of collagen from calf skin
      2 mg bupivacaine;
    2.  30 mg of collagen from bovine skin
      2 mg of bupivacaine;
    3.  35 mg of collagen from bovine skin
      3 mg of lidocaine;
    4.  40 mg of collagen from bovine skin
      3 mg of lidocaine;
    5.  50 mg of collagen from calf skin
    3.5 mg of bupivacaine.
    • Application Example 1
  • A young women, 32 years old, with therapy-resistant gonalgia, was treated about 1½ years ago with injections of 0.5 ml of the collagen-containing injection suspension according to example 3 intraarticularily into the joints on the one side and 1.0 ml on the other side; subsequently she was completely symptom-free. It was not necessary to repeat the treatment. [0019]
    • Application Example 2
  • Injections in the case of an extension of the hip joint resulted in an improvement following prior injection of 2 ml of local anaesthetic only for the purpose of the correct needle position, after 2 ml of the collagen injection suspension according to example 5 had been infiltrated intraarticularly into each joint side. The observation time was approximately two years. It was found that, above all, the initial, primary arthrotic complaints had come to a complete standstill after 6 months. [0020]
  • Further similar case reports are available. [0021]
    • Application Example 3
  • Intraarticular injections of 1 ml of the collagen-containing injection suspension according to example 3 brought about an approx. 70% improvement of the complaints according to the patient's statement in the case of a left-side severe gonarthrosis. Since about 2 years, the complaints have remained constant. [0022]

Claims (5)

1. Use of collagen for producing a drug for the treatment of arthropathies, characterized in that the collagen is contained in an injection suspension.
2. Use according to
claim 1
, characterized in that the amount of the collagen contained in the injection suspension is about 20 to 50 mg/ml.
3. Use according to any of claims 1 or 2, characterized in that a local anaesthetic is also contained.
4. Use according to
claim 3
, characterized in that the amount of the local anaesthetic contained in the injection suspension is 1 to 5 mg/ml.
5. Use according to any of
claims 1
 to
4
, characterized in that the collagen contained in the drug is collagen from bovine skin.
US09/680,569 1991-07-31 2000-10-05 Use of collagen for the treatment of degenerative articular processes Abandoned US20010056069A1 (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
US09/680,569 US20010056069A1 (en) 1991-07-31 2000-10-05 Use of collagen for the treatment of degenerative articular processes

Applications Claiming Priority (5)

Application Number Priority Date Filing Date Title
DEP4125400.7 1991-07-31
DE4125400A DE4125400C2 (en) 1991-07-31 1991-07-31 Use of insoluble collagen for the treatment of degenerative, non-inflammatory joint processes
US08/050,184 US6083918A (en) 1991-07-31 1992-07-28 Use of collagen for the treatment of degenerative articular processes
US09/401,377 US6165983A (en) 1991-07-31 1999-09-22 Use of collagen for the treatment of degenerative articular processes
US09/680,569 US20010056069A1 (en) 1991-07-31 2000-10-05 Use of collagen for the treatment of degenerative articular processes

Related Parent Applications (1)

Application Number Title Priority Date Filing Date
US09/401,377 Continuation US6165983A (en) 1991-07-31 1999-09-22 Use of collagen for the treatment of degenerative articular processes

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US20010056069A1 true US20010056069A1 (en) 2001-12-27

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US08/050,184 Expired - Fee Related US6083918A (en) 1991-07-31 1992-07-28 Use of collagen for the treatment of degenerative articular processes
US09/401,377 Expired - Fee Related US6165983A (en) 1991-07-31 1999-09-22 Use of collagen for the treatment of degenerative articular processes
US09/680,569 Abandoned US20010056069A1 (en) 1991-07-31 2000-10-05 Use of collagen for the treatment of degenerative articular processes

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US08/050,184 Expired - Fee Related US6083918A (en) 1991-07-31 1992-07-28 Use of collagen for the treatment of degenerative articular processes
US09/401,377 Expired - Fee Related US6165983A (en) 1991-07-31 1999-09-22 Use of collagen for the treatment of degenerative articular processes

Country Status (4)

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US (3) US6083918A (en)
JP (1) JPH082797B2 (en)
DE (1) DE4125400C2 (en)
WO (1) WO1993002699A1 (en)

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US20040228850A1 (en) * 2003-04-07 2004-11-18 Mcewen Simon Therapeutic composition for autoimmune conditions
US11534419B2 (en) 2011-04-13 2022-12-27 Thermolife International, Llc N-acetyl beta alanine methods of use
US11865139B2 (en) 2020-11-12 2024-01-09 Thermolife International, Llc Method of treating migraines and headaches
US12156886B2 (en) 2020-11-12 2024-12-03 Thermolife International, Llc Methods of increasing blood oxygen saturation
US12227483B1 (en) 2007-09-18 2025-02-18 Thermolife International, Llc Amino acid compositions
US12441615B2 (en) 2021-02-11 2025-10-14 Thermolife International, Llc Method of administering nitric oxide gas

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US5843445A (en) * 1987-06-24 1998-12-01 Autoimmune, Inc. Method of treating rheumatoid arthritis with type II collagen
US5849298A (en) * 1987-06-24 1998-12-15 Autoimmune Inc. Treatment of multiple sclerosis by oral administration of bovine myelin
US5869054A (en) * 1987-06-24 1999-02-09 Autoimmune Inc. Treatment of multiple sclerosis by oral administration of autoantigens
US6645504B1 (en) 1987-06-24 2003-11-11 Autoimmune Inc. Bystander suppression of type I diabetes by oral administration of glucagon
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DE4329668C2 (en) * 1993-09-02 2001-05-17 Werner Pruegner Use a sterile collagen solution for tendon injuries
US6645485B2 (en) * 2000-05-10 2003-11-11 Allan R. Dunn Method of treating inflammation in the joints of a body
US7119062B1 (en) 2001-02-23 2006-10-10 Neucoll, Inc. Methods and compositions for improved articular surgery using collagen
US20040054414A1 (en) * 2002-09-18 2004-03-18 Trieu Hai H. Collagen-based materials and methods for augmenting intervertebral discs
USRE47826E1 (en) 2007-03-28 2020-01-28 Innocoll Pharmaceuticals Limited Drug delivery device for providing local analgesia, local anesthesia or nerve blockage
LT3085363T (en) * 2007-03-28 2019-06-25 Innocoll Pharmaceuticals Limited A drug delivery device for providing local analgesia, local anesthesia or nerve blockade
WO2008151040A2 (en) * 2007-05-31 2008-12-11 Cook Biotech Incorporated Analgesic coated medical product
US8679176B2 (en) 2007-12-18 2014-03-25 Cormatrix Cardiovascular, Inc Prosthetic tissue valve
US8257434B2 (en) 2007-12-18 2012-09-04 Cormatrix Cardiovascular, Inc. Prosthetic tissue valve
WO2010096458A1 (en) 2009-02-18 2010-08-26 Cormatrix Cardiovascular, Inc. Compositions and methods for preventing cardiac arrhythmia
CA2835862A1 (en) 2011-05-27 2012-12-06 Cormatrix Cardiovascular, Inc. Extracellular matrix material valve conduit and methods of making thereof
US10226513B2 (en) 2015-01-09 2019-03-12 Mark Terrell Smith Method and composition to prevent or improve symptoms of musculoskeletal distress degeneration
EP3621985A4 (en) 2017-05-11 2021-03-17 Avicenna Nutraceutical, LLC COLLAGEN PRODUCTION PROCESSES

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US20040228850A1 (en) * 2003-04-07 2004-11-18 Mcewen Simon Therapeutic composition for autoimmune conditions
US7901676B2 (en) * 2003-04-07 2011-03-08 Epidyme Limited Therapeutic composition for the treatment of rheumatoid arthritis
US20110135624A1 (en) * 2003-04-07 2011-06-09 Mcewen Laboratories, Ltd. Therapeutic composition for autoimmune conditions
US12448357B1 (en) 2007-09-18 2025-10-21 Thermolife International, Llc Amino acid compositions
US12227483B1 (en) 2007-09-18 2025-02-18 Thermolife International, Llc Amino acid compositions
US12240819B1 (en) 2007-09-18 2025-03-04 Thermolife International, Llc Amino acid compositions
US12473261B2 (en) 2007-09-18 2025-11-18 Thermolife International, Llc Amino acid compositions
US12522568B2 (en) 2007-09-18 2026-01-13 Thermolife International, Llc Amino acid compositions
US12540119B2 (en) 2007-09-18 2026-02-03 Thermolife International, Llc Amino acid compositions
US11534419B2 (en) 2011-04-13 2022-12-27 Thermolife International, Llc N-acetyl beta alanine methods of use
US11865139B2 (en) 2020-11-12 2024-01-09 Thermolife International, Llc Method of treating migraines and headaches
US12156886B2 (en) 2020-11-12 2024-12-03 Thermolife International, Llc Methods of increasing blood oxygen saturation
US12441615B2 (en) 2021-02-11 2025-10-14 Thermolife International, Llc Method of administering nitric oxide gas

Also Published As

Publication number Publication date
JPH082797B2 (en) 1996-01-17
WO1993002699A1 (en) 1993-02-18
US6165983A (en) 2000-12-26
US6083918A (en) 2000-07-04
JPH06501500A (en) 1994-02-17
DE4125400C2 (en) 2000-08-17
DE4125400A1 (en) 1993-02-04

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