US3400199A - Wound-healing cartilage powder - Google Patents

Wound-healing cartilage powder Download PDF

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Publication number
US3400199A
US3400199A US435693A US43569365A US3400199A US 3400199 A US3400199 A US 3400199A US 435693 A US435693 A US 435693A US 43569365 A US43569365 A US 43569365A US 3400199 A US3400199 A US 3400199A
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cartilage
wound
healing
powder
wounds
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US435693A
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Leslie L Balassa
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Lescarden Ltd
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Individual
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Priority to USRE28093D priority Critical patent/USRE28093E/en
Priority to CH239763A priority patent/CH479304A/de
Application filed by Individual filed Critical Individual
Priority to US435693A priority patent/US3400199A/en
Priority to DE1617317A priority patent/DE1617317B2/de
Priority to FR1590066D priority patent/FR1590066A/fr
Priority to CH282466A priority patent/CH479305A/de
Priority to GB8762/66A priority patent/GB1121636A/en
Priority to US698426A priority patent/US3476855A/en
Priority to US698387A priority patent/US3478146A/en
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Publication of US3400199A publication Critical patent/US3400199A/en
Assigned to LESCARDEN INC., reassignment LESCARDEN INC., CHANGE OF NAME (SEE DOCUMENT FOR DETAILS). EFFECTIVE JAN. 12,1983 Assignors: LESCARDEN LTD.
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Expired - Lifetime legal-status Critical Current

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS 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
    • A61L2/00—Methods or apparatus for disinfecting or sterilising materials or objects other than foodstuffs or contact lenses; Accessories therefor
    • A61L2/0005—Methods or apparatus for disinfecting or sterilising materials or objects other than foodstuffs or contact lenses; Accessories therefor for pharmaceuticals, biologicals or living parts
    • A61L2/0011—Methods or apparatus for disinfecting or sterilising materials or objects other than foodstuffs or contact lenses; Accessories therefor for pharmaceuticals, biologicals or living parts using physical methods
    • A61L2/0023—Heat
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
    • A61K35/12—Materials from mammals; Compositions comprising non-specified tissues or cells; Compositions comprising non-embryonic stem cells; Genetically modified cells
    • A61K35/32—Bones; Osteocytes; Osteoblasts; Tendons; Tenocytes; Teeth; Odontoblasts; Cartilage; Chondrocytes; Synovial membrane

Definitions

  • This invention relates to wound-healing compositions and methods of making, improving and reaetivating the same, and methods of treating and healing wounds.
  • cartilage taken from the partly calcified skeletons (including foetal skeletons) of very young or newly born animals is much more effective in accelerating the healing of wounds than was the case with the bovine tracheal cartilage powder on which previous observations were based, which included substantial quantities of coarse adult cartilage powder.
  • the young animal is not over six months old.
  • the cartilage may be prepared by any suitable means to result in a product which is essentially pure cartilage substance free from adhering tissue, which may have been removed by acid-pepsin or other suitable enzyme treatment, with or without mechanical assistance, or otherwise.
  • extraction aids those which are either volatile and therefore can be readily removed from the extract by volatilization such as for example ammonia or ammonium carbonate, or such materials which if remaining in the extract would cause no harm if applied either topically or introduced parenterally.
  • Dialysis may be employed to remove undesired salts or other dialyzable material which may be present.
  • Other extraction aids are urea, sodium citrate, disodium phosphate, trisodium phosphate, sodium formate, sodium chloride, and similar compounds or mixtures of them.
  • the present invention provides dosage units of effective wound healing quantity of cartilage powder from a young animal, or from a mature animal, having average particle size between about 1 micron and about 40 mircons, or a substantial maximum particle size of about 70 microns, incorporated into a clinically acceptable wound healing carrier vehicle such as unguent, oil, salve, solution, extract, powder, etc.
  • a clinically acceptable wound healing carrier vehicle such as unguent, oil, salve, solution, extract, powder, etc.
  • the invention also contemplates methods of enhancing the wound healing actvity of a cartridge powder and of restoring wound healing activity in substantially inactivated cartilage powder including partially deactivated cartilage powder. Novel methods are also provided whereby finely divided cartilage powder may be stabilized before, during or after the final comminution stage of production thereof.
  • Various techniques for the extraction of active wound healing components, agents, and compositions from cartilage powder are included within the present invention.
  • the invention has been used with humans in treatment of keloids (hardened scar tissue),
  • the keloid was initial- 1y cut out, and resutured in the presence of the calf cartilage powder of the invention. After more than six months periodic observation, the keloid did not reappear and apparently the invention prevented the re-formation of the keloid scar tissue, contrary to the usual experience of frequent recurrence of keloid formation.
  • the local use of the finely ground calf cartilage powder is of great clinical value in the treatment of nongranulating wounds of 50 different kinds, without untoward effects, either locally or systemically, as demonstrated in application to the primarily closed wounds of 87 human surgical incisions in a wide variety of procedures. There was no immediate or late evidence of antigenicity.
  • the cartilage preparations of the present invention have been successfully utilized to accelerate and to improve the healing of the following types of wounds, either by topical application or by injection of saline extract: chemical burns, third degree skin burns, radioactive injury, chest wall, abdominal and other wounds, operative and post-operative wounds, penetrating wounds such as those of thorax and abdomen, ulcers due to arteriosclerosis and t0 trophic disturbance, ulcers of skin, gangrene of skin due to trauma or physical agent or to undetermined cause, dermatitis, lupus erythemathosus with ulcer, keloids, atopic eczema, parapsoriasis and psoriasis.
  • Other types of wounds also have responded successfully to the cartilage preparations of this invention with improved results.
  • the invention is especially useful in cases involving cortisone or other steroid treat ment (known to retard healing) or involving diabetes.
  • the wound tensile strength at seven days is determined in millimeters of mercury by a modification of the technique of the method illustrated in the publication cited above.
  • the rat to be tested is killed by an intracardiac injection of paraldehyde or by exposure to toxic fumes such as to diethyl ether.
  • the test is made prior to the onset of rigor mortis.
  • a rubber latex prophylactic pouch is inserted into the peritoneal cavity through a defect made with a Kelly clamp in the apex of the vagina.
  • the rotary air pump connected to the pouch is turned on regulating it in such a manner that the air pressure will increase at a rate of millimeters of mercury every five seconds.
  • the pressure at which the wound splits and the pouch extrudes itself (wholly or in part) through the defect is recorded as the tensile strength of the wound. This is also a quantitative measure of the degree of healing or rate of healing achieved in the experiments.
  • EXAMPLE l.CARTILAGE PEBBLE MILL-GROUND The tracheas of healthy adult beef cattle were removed within 30 to 60 minutes after the animals were slaughtered. The tracheas were then either processed immediately with an acidpepsin solution or they were frozen to preserve them, in which case the acid-pepsin digestion may be deferred. The tracheas either fresh or previously frozen were then digested for about six hours at 50 C. in an aqueous solution containing 0.6% acetic acid (U.S.P. glacial) and 0.3% pepsin (NF. IX grade, 3500 activity). After digestion the tracheal cartilage was removed from the acid-pepsin solution, washed first with water of about 70 C.
  • U.S.P. glacial 0.6% acetic acid
  • pepsin NF. IX grade, 3500 activity
  • the granulated purified cartilage was ground to a fine powder in a laboratory four-quart size porcelain jar mill, loaded with one-inch size (average) fiint pebbles in a weight ratio of 1 cartilage to 2 pebbles. Dry Ice (CO was then put on top of the mill charge and the mill was kept open for 5 minutes to allow the CO to displace the air in the mill. The lid of the mill was then clamped on tight and the mill rotated as is customary in the performance of the grinding operation. The grinding was carried out at about 20 C. for 96 hours.
  • the ground cartilage was screened through a 325 mesh nylon screen, thereby confining the active cartilage powder to particles less than about 40 microns in size, and having average or majority particle size between about 5 and 10 microns.
  • Example 1 the same procedure was followed as described in Example 1 in the preparation of the cartilage powder of the invention, except that grinding times differed to obtain different grinds, and the cartilage source in Example l-C was great white shark jaw cartilage which was ground in a mechanical mortar.
  • the test method described above was performed to compare the rate of wound healing of each Example 1-A, 1-B and 1-C with control wounds which were untreated. The percent of wound healing stated was 100% for the control and represented increases as stated below for the examples of the invention, each figure representing the average of about 20 to over 40 controlled pairs of tests:
  • Example Cartilage used particle size healing (percent) C0ntr0l N 100 A Approx. 70 1-B do Approx. 20;i 152. 5 1-0 Great white shark jaw Approx. 70 130 EXAMPLE 2.CARTILAGE PEBBLE MILL-GROUND Cartilage obtained from the skeleton of a two-day old piglet was washed with distilled water immediately after removal from the carcass. The cartilage was then freed from the adhering tissue matter and then digested with an acid-pepsin solution was described in Example 1. The cartilage was ground and screened in accordance with the method described in Example 1.
  • the cartilage was acid-pepsin digested as in Example 1, granulated, and then without drying was suspended in the extracting liquid and then transferred into pebble mill which was charged to 50% of its volume with flint pebbles of average size, one inch diameter.
  • the ratio of the cartilage to extracting liquid was kept to 25 :75.
  • the liquid suspension was charged into the mill in a quantity just sufiicient to fill the voids of the pebbles with the top of the pebbles barely covered by the liquid.
  • the air was then purged from the mill with nitrogen and the mill closed.
  • the mill was allowed to run for 6 hours at between 3 C. and 4 C. which resulted in a medium fine grinding of the cartilage and in the simultaneous extraction of the active wound-healing agent from the cartilage.
  • the extracts were stored at 4 C. preserved with 1:10,000 sodium ethyl mercuric thiosalicylate.
  • EXAMPLE 6 SPRAY-DRYING OF CARTILAGE EXTRACTS Dry concentrates were prepared from cartilage extracts as follows:
  • a laboratory Bowen type spray dryer was used with the following modifications. In place of the oil furnace, electric heating coils were used to supply the heat energy necessary for the evaporation of the volatile portions of the extracts. Instead of air, nitrogen was used for the hot gas. A vaned disc, rotating at about 20,000 rpm. was used to atomize the extracts. The inlet gas temperature was held to about 280 F., the outlet temperature was between F. and F. The dryer was used as a closed system dryer with the exclusion of oxygen to avoid degrading the active material during the evaporation of the water.
  • the solids percent means percent of solids in the extracting liquid as determined by drying at 100 C. for two hours.
  • Yield percent means the dry solids percent obtained from the liquid by the drying process.
  • the spray-dried powders were stored in tightly closed glass jars in a refrigerator at 4 C.
  • Example 5 Extract used Solids, Yield, Appearance of dried percent percent material a Example 5-1).... 5. 2 5. 1 Off white coarse powder. b. Example 5c 6. 5 6.5 Do. 0. 7. 6 7. 8 Do. d. 9. 2 l0. 1 Do. a... 6. 4 6. 5 Do. 11. Example 5-m. 7. 1 7. 3 Do. g.- Example 5-0.... 10.0 10.8 Do. h Example 5p 6.2 6. 3 Do. i Example 5q..- 7.2 7. 6 Do. 1 Example 5r... 8.2 8.5 Do.
  • freeze-dried materials were stored in tightly closed glass ars in a refrigerator at 4 C.
  • EXAMPLE 8 Cartilage powders are applied to wounds by dusting with a hand atomizer about 30 mg. into a 5.75 cm. longitudinal midline abdominal incision of the female rat. Of the 30 mg. applied to the wounds about 10-15 mg. was effectively utilized at the sites of the wound. It is preferred that the dosage unit be applied to the wound in an amount substantially equivalent to between about lO-lS mg. per square centimeter.
  • Rate of wound Cartilage powder healing (percent) 1. None, control 100 2.
  • Example 4q 135 Rate of wound healing related to 100 means the ratio, expressed as percent, of pressure required to rupture the healed tissue of the wound as compared with the pressure required for rupture of the wound of the untreated control animal, according to the test method described above.
  • EXAMPLE 9 Cartilage extracts applied to wounds by swabbing to 5.75 cm. longitudinal midline abdominal incision of the female rat.
  • Example 5-a 105 3.
  • Example 5-b 120 4.
  • Example 5 125 5.
  • Example 5-i 130 6.
  • Example 5-l 135 7.
  • Example 5-p 135 8.
  • Example 5-r 140 EXAMPLE 11 This example demonstrates the effect of parenterally injected cartilage extracts combined with a bovine growth 10 hormone. In each case 5 cc. of the extract was mixed with 10 mgm. of a bovine growth hormone, distributed by the Endocrinology Study Section of the National Institutes of Health through the pituitary hormone distribution program. Approximate assay of the growth hormone:
  • Rate of wound Cartilage extract (liquid): healing (percent)
  • rate of wound Cartilage extract (liquid): healing (percent)
  • the dried extracts were dissolved either in water or in isotonic saline solution, depending on the salt content of the original preparation. The solutions were adjusted to correspond with the solids content of the extracts from which the dried materials were prepared. The solutions were applied by parenteral injections into rats as in Example 10.
  • Example 7-j do 145 EXAMPLE 13 This example demonstrates the value of intravenous injections of cartilage extracts or solutions of dried extracts in the healing of wounds. These were made on dogs with circular incisions. Wounds were not saturated but protected only with sterile dressing. The rate of healing was measured by observing the degree of granulation as compared with the control.
  • Rate of wound Extract healing (percent) 1. None, isotonic saline-control 100 2.
  • Example 5-b 120 3.
  • Example 5-l 135 4.
  • Example 5p 135 5.
  • Example 5-r 140 6.
  • Examples 12-10 140 7.
  • Examples 12-11 145 EXAMPLE 14 This example demonstrates the use of cartilage powder on open Wounds. Powders were held between layers of porous fabric, i.e., surgical gauze, and held through band- 1 1 ages to the unsutured wound. Tests were made on dogs. The rate of healing was estimated by observing the degree of granulation.
  • Rate of wound Cartilage powder healing (percent) 1. None, dry gauzecontrol 100 2.
  • Example 2 135 3.
  • Example 4-) 135 4.
  • Example 4-m 145 EXAMPLE 15 This example demonstrates the effect of applying liquid cartilage extracts on open wounds. Porous fabric, i.e., surgical gauze was saturated with the extracts and applied to the open and unsutured wounds while still wet. Tests were made on dogs. The rate of healing was measured by the observed degree of granulation.
  • Rate of wound Cartilage extract healing (percent) 1. None, isotonic saline-control 100 2.
  • Example S-r 150 EXAMPLE 17 These tests involved the intravenous injection of cartilage extracts combined with one or more blood extenders, such as whole blood, blood plasma, and a plasma substitute, namely polyvinylpyrrolidone or dextran. Tests were made on dogs. In carrying out these tests 100 cc. blood was taken from the animal and treated as follows:
  • the blood was mixed with cc. cartilage extract and reinjected into the same animal.
  • EXAMPLE l8.-CARTILAGE SUPPOSITORIES Suppositories were prepared with 20% cartilage powder and suppository base.
  • the suppository base was prepared in accordance with U.S.P. XVI, pages 828-9, Glycerinated Gelatin Suppositories.
  • the suppositories were 2 gm. size and were administered rectally to dogs. The surface of the rectum was removed for 1 cm. from the rectal opening, about one hour before the insertion of the suppository. A fresh suppository was introduced every six hours. The rate of healing was determined by visual observation.
  • the calf cartilage powder of the invention Mix the calf cartilage powder of the invention with an excess of about 70% (volume) ethyl alcohol. A sufficient excess of alchol is present when the cartilage powder forms a mobile slurry with the powder.
  • the particle size of the powder controls the volume of alcohol required to form the mobile slurry. The smaller the particle size the larger the volume of alcohol is required.
  • the alcohol slurry of the cartilage powder is best mixed at a rate to keep the powder suspended in the liquid.
  • the cartilage swells somewhat and becomes gummy under the influence of the 70% alcohol.
  • the cartilage sediment mixed with the anhydrous alcohol, is dehydrated regaining substantially its original particle size and losing its gumminess. This dehydrated cartilage can be readily filtered and dries to a free flowing powder.
  • EXAMPLE 22.STERILIZATION WITH ISOPROPYL ALCOHOL Anhydrous isopropyl alcohol sterilizes the cartilage as well as 70% ethyl alcohol and in about the same time, i.e., about 30 minutes, without swelling the cartilage particles or causing gumminess.
  • the cartilage slurry prepared with isopropyl alcohol can be readily filtered and the filter cake so obtained can be dried to a free flowing powder.
  • the sterilization either with ethyl alcohol or with isopropyl alcohol can be carried out satisfactorily at ambient room temperatures, although sterilization at elevated temperatures may reduce the time required.
  • the heat sterilized powder is ready for clinical use.
  • the cartilage powder was inactivated by hammer milling it under conditions of excessive aeration and some generation of heat (Test 5).
  • Comparison of Test 3 with Test 2 shows that heat sterilization of the powder of this invention may be accomplished together with enhancement (130.5 vs. 127.7%) of wound healing rate.
  • EXAMPLE 26 The cartilage powder of the invention was atomized into 83 surgical wounds in 39 human patients with 47 operations, as follows:
  • cartilage with substantially greater potency is obtained from the skeletons of very young animals.
  • the highest potency material is generally obtained from animals less than one month old, although cartilage from adolescent animals taken before maturity may be used in this invention without excessively fine grinding. Young animals are intended to mean those which are still adolescent and have not yet reached maturity. Cartilage from foetal skeletons is often etfective.
  • Finely divided cartilage from other mammals, in addition to bovine and porcine and canine, is effective in healing wounds in accordance with the present invention: for example, finely divided cartilage powder from rat trachea and the human knee have been successfully utilized in accordance with the invention; so also with other animals such as the finely divided cartilage of birds, fish, jaw-bone of shark, rib cage of a crocodile (South American caiman known to be one year old, as obtained from the New York City Zoological Gardens, in early adsolescence). Finely divided reptile cartilage is particularly etfective in view of the extraordinary ability of the reptiles to regenerate their tissues and even their limbs.
  • the cartilage powder may be dusted on the wound or atomized on it. It may also be applied in the form of ointment on the wound, as exemplified above.
  • the extract may also be applied directly to the wound by spraying it on the wound, swabbing it on, or brushing it on. Both the powder and the extract may be applied first to an absorbent medium which is then applied to the wound and held on by a bandage or adhesive tape, or other suitable means.
  • the cartilage or the extract may be incorporated into tablets, capsules or suppositories and applied orally, rectally or in the vaginal or uteral passages. Implantation as pellets and injection of solution of the extract of the invention has been effective.
  • Cartilage extracts may be injected subcutaneously, intramuscularly or intravenously.
  • the dried extract may be used as powders or they may be reconstituted and used as the original extracts.
  • the wounds to which the active materials are applied may be sutured or may be left open without materially affecting the rate of healing.
  • the active materials may be administered once, preferably within the first 24 hours of the incision; or they may be applied before the incision or they may be applied in several applications in succession. Irradiating the cartilage powder with ultraviolet radiation in the absence of oxygen increases its activity.
  • a non-interposing cartilage powder from a cartilagecontaining animal having an average particle size between about 1 micron and about 40 microns and having a substantial maximum particle size of about 70 microns.
  • a dosage unit according to claim 1 comprising an elfective wound-healing quantity of a noninterposing cartilage powder having a substantial maximum particle size of about 70 microns and an average particle size between about 1 micron and about 40 microns derived from shark or reptilian cartilage.
  • Prudden et al. Surg. Gyn. Obst. 283486, September 1957.

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US435693A 1962-02-28 1965-02-26 Wound-healing cartilage powder Expired - Lifetime US3400199A (en)

Priority Applications (9)

Application Number Priority Date Filing Date Title
USRE28093D USRE28093E (en) 1962-02-28 Wound-healing cartilage powder
CH239763A CH479304A (de) 1962-02-28 1963-02-25 Verfahren zur Herstellung eines die Wundheilung fördernden Stoffes
US435693A US3400199A (en) 1965-02-26 1965-02-26 Wound-healing cartilage powder
DE1617317A DE1617317B2 (de) 1965-02-26 1966-02-25 Knorpelmasse
FR1590066D FR1590066A (enrdf_load_stackoverflow) 1965-02-26 1966-02-26
CH282466A CH479305A (de) 1965-02-26 1966-02-28 Verfahren zur Herstellung von die Wundheilung fördernden Wirkstoffen aus Knorpelmasse
GB8762/66A GB1121636A (en) 1965-02-26 1966-02-28 Improved wound healing compositions
US698426A US3476855A (en) 1965-02-26 1968-01-17 Sterilizing and enhancing activity of a finely divided cartilage powder
US698387A US3478146A (en) 1965-02-26 1968-01-17 Wound-healing cartilage powder extracting process

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US435693A US3400199A (en) 1965-02-26 1965-02-26 Wound-healing cartilage powder

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US435693A Expired - Lifetime US3400199A (en) 1962-02-28 1965-02-26 Wound-healing cartilage powder

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CH (1) CH479305A (enrdf_load_stackoverflow)
DE (1) DE1617317B2 (enrdf_load_stackoverflow)
FR (1) FR1590066A (enrdf_load_stackoverflow)
GB (1) GB1121636A (enrdf_load_stackoverflow)

Cited By (46)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3476855A (en) * 1965-02-26 1969-11-04 Leslie L Balassa Sterilizing and enhancing activity of a finely divided cartilage powder
US3478146A (en) * 1965-02-26 1969-11-11 Leslie L Balassa Wound-healing cartilage powder extracting process
US3786888A (en) * 1972-05-22 1974-01-22 Lockheed Missiles Space Torque compensated walking beam
US3966908A (en) * 1973-11-29 1976-06-29 Lescarden Ltd. Method of treating degenerative joint afflictions
US4058213A (en) * 1976-07-06 1977-11-15 Irwin Stone Low temperature vapor phase sterilization and storage of biologically active injectable materials
WO1980000059A1 (en) * 1973-10-24 1980-01-24 H Robertson Medical protein hydrolysate and process of using the same
US4216204A (en) * 1978-05-08 1980-08-05 Robertson Harry J Medical protein hydrolysate, process of making the same and processes of utilizing the protein hydrolysate to aid in healing traumatized areas
WO1980002501A1 (en) * 1979-05-11 1980-11-27 Lescarden Ltd Cartilage extraction processes and products
US4291013A (en) * 1978-10-09 1981-09-22 Merck Patent Gesellschaft Mit Beschrankter Haftung Medicinally useful, shaped mass of collagen resorbable in the body
US4444752A (en) * 1982-09-13 1984-04-24 Lescarden Ltd. Method for treating progressive systemic sclerosis
US4473551A (en) * 1982-08-23 1984-09-25 Faxon Pharmaceuticals, Inc. Anti-inflammatory composition
US4587268A (en) * 1980-09-03 1986-05-06 Ed. Geistlich Sohne A.G. Fur Chemische Industrie Treatment of osteitis
US4806523A (en) * 1985-08-06 1989-02-21 Collagen Corporation Method of treating inflammation
US5529982A (en) * 1985-08-06 1996-06-25 Celtrix Pharmaceuticals, Inc. Inducing granulocyte production or B cell production in peripheral blood by TGF-β
US5733884A (en) * 1995-11-07 1998-03-31 Nestec Ltd. Enteral formulation designed for optimized wound healing
WO1998036760A1 (en) * 1997-02-20 1998-08-27 Industrial Research Limited Angiogenesis inhibitors and activators from shark cartilage
US20050260181A1 (en) * 2004-03-05 2005-11-24 Immunopath Profile, Inc. Compositions and methods for tissue repair
US20050288796A1 (en) * 2004-06-23 2005-12-29 Hani Awad Native soft tissue matrix for therapeutic applications
US20060251612A1 (en) * 2005-05-09 2006-11-09 Dimiter Kotzev Bioresorbable cyanoacrylate adhesives
US20070037777A1 (en) * 2005-08-12 2007-02-15 Immunopath Profile, Inc. Lipid-containing compositions and methods of using them
US20070231402A1 (en) * 1994-08-02 2007-10-04 Immunopath Profile, Inc. Therapeutic stem cell composition and stimulant, facilitator, accelerator, and synergizer thereof, growth factor, anti-inflammatory composition and uses thereof
US7488348B2 (en) 2003-05-16 2009-02-10 Musculoskeletal Transplant Foundation Cartilage allograft plug
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US7790678B1 (en) 1999-08-17 2010-09-07 Immunopath Profile, Inc. Composition with anti-inflammatory, protein synthesizing, enzyme deficiency activating genetic therapy and anti-cancer activity and methods of use
US20100241228A1 (en) * 2006-07-07 2010-09-23 Carina Syring Engineered osteochondral construct for treatment of articular cartilage defects
US20100274362A1 (en) * 2009-01-15 2010-10-28 Avner Yayon Cartilage particle tissue mixtures optionally combined with a cancellous construct
US7837740B2 (en) 2007-01-24 2010-11-23 Musculoskeletal Transplant Foundation Two piece cancellous construct for cartilage repair
US20100322994A1 (en) * 2003-12-11 2010-12-23 Isto Technologies, Inc. Particulate cartilage system
US7901457B2 (en) 2003-05-16 2011-03-08 Musculoskeletal Transplant Foundation Cartilage allograft plug
USRE42208E1 (en) 2003-04-29 2011-03-08 Musculoskeletal Transplant Foundation Glue for cartilage repair
US20110070271A1 (en) * 2004-10-12 2011-03-24 Truncale Katherine G Cancellous constructs, cartilage particles and combinations of cancellous constructs and cartilage particles
WO2012143324A1 (en) 2011-04-19 2012-10-26 Bioiberica, S.A. Cartilage product
US8435551B2 (en) 2007-03-06 2013-05-07 Musculoskeletal Transplant Foundation Cancellous construct with support ring for repair of osteochondral defects
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US8480757B2 (en) 2005-08-26 2013-07-09 Zimmer, Inc. Implants and methods for repair, replacement and treatment of disease
US8497121B2 (en) 2006-12-20 2013-07-30 Zimmer Orthobiologics, Inc. Method of obtaining viable small tissue particles and use for tissue repair
US8673362B2 (en) 1999-08-17 2014-03-18 Immunopath Profile, Inc. Therapeutic stem cell nutrient composition and uses thereof
US9138318B2 (en) 2007-04-12 2015-09-22 Zimmer, Inc. Apparatus for forming an implant
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DE1617317A1 (de) 1971-03-25
CH479305A (de) 1969-10-15
GB1121636A (en) 1968-07-31
DE1617317C3 (enrdf_load_stackoverflow) 1978-12-21
FR1590066A (enrdf_load_stackoverflow) 1970-04-13
DE1617317B2 (de) 1978-04-20

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