US3830910A - Pseudo-synovial plastic body fluids and method of preparing same - Google Patents

Pseudo-synovial plastic body fluids and method of preparing same Download PDF

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Publication number
US3830910A
US3830910A US00235311A US23531172A US3830910A US 3830910 A US3830910 A US 3830910A US 00235311 A US00235311 A US 00235311A US 23531172 A US23531172 A US 23531172A US 3830910 A US3830910 A US 3830910A
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US
United States
Prior art keywords
sodium carboxymethylcellulose
pseudo
fluid
synovial fluid
synovial
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 - Lifetime
Application number
US00235311A
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English (en)
Inventor
C Homsy
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.)
TRANQUIL PROSPECTS Ltd A Co OF BRITISH VIRGIN ISLANDS
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Individual
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 Individual filed Critical Individual
Priority to US00235311A priority Critical patent/US3830910A/en
Priority to CA165,323A priority patent/CA1011251A/en
Priority to GB1135273A priority patent/GB1391577A/en
Priority to IE377/73A priority patent/IE37384B1/xx
Priority to ZA731754A priority patent/ZA731754B/xx
Priority to NL7303596A priority patent/NL7303596A/xx
Priority to AU53312/73A priority patent/AU475354B2/en
Priority to SE7303611A priority patent/SE425143B/xx
Priority to FR7309303A priority patent/FR2181824B1/fr
Priority to JP48030162A priority patent/JPS49417A/ja
Priority to BE128884A priority patent/BE796883A/xx
Priority to DE2313221A priority patent/DE2313221A1/de
Application granted granted Critical
Publication of US3830910A publication Critical patent/US3830910A/en
Assigned to NOVAMED, INC., HOUSTON, TX, A CORP. OF TX reassignment NOVAMED, INC., HOUSTON, TX, A CORP. OF TX ASSIGNMENT OF ASSIGNORS INTEREST. Assignors: HOMSY, CHARLES A., VITEK, INC., A TX CORP.
Assigned to TRANQUIL PROSPECTS, LTD., A COMPANY OF THE BRITISH VIRGIN ISLANDS reassignment TRANQUIL PROSPECTS, LTD., A COMPANY OF THE BRITISH VIRGIN ISLANDS ASSIGNMENT OF ASSIGNORS INTEREST. Assignors: NOVAMED, INC., A CORP. OF TX
Anticipated expiration legal-status Critical
Expired - Lifetime legal-status Critical Current

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Classifications

    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K33/00Medicinal preparations containing inorganic active ingredients
    • A61K33/42Phosphorus; Compounds thereof

Definitions

  • the fluid is prepared by adding the salts and preservative to water being stirred at high speed and thereafter the sodium carboxymethylcellulose is slowly added and stirred into the liquid.
  • synovial fluid is normally present in human bodies in the cavities of the freely movable joints, in the bursae and within tendon sheaths, particularly where the tendons change their direction and pass under or through the fibrous slings or bony prominences. Such fluid appears to function as a lubricant and a shock absorbing medium. It is believed that the visco-elastic or pseudo-plasticity of the synovial fluid contributes crucially to optimum joint function.
  • the synovial fluid has the property of having an apparent viscosity increase as the rate of shear applied is decreased.
  • the viscosity and pseudo-plasticity of synovial fluid is sharply impaired as a result of pathological conditions such as rheumatoid arthritis, osteoarthritis and trauma.
  • the resulting impairment of lubrication ability would predispose the articulating surfaces of the joint to premature wear trauma.
  • the present invention relates to an improved fluid having substantially the same rheological proper-ties as human synovial fluid.
  • An object of the present invention is to provide a pseudo-synovial fluid suitable for injection into a joint to replace or augment synovial fluid to prevent additional "ice
  • Another object is to provide an improved pseudosynovial fluid which is stable for storing at room temperatures and which can be sterilized by boiling or autoclaving.
  • a still further object is to provide a pseudo-plastic fluid having properties close to body fluids exhibiting pseudoplasticity.
  • ovial fluid may be considered to be a dialysate of blood plasma with the addition of hyaluronic acid.
  • Hyaluronic acid is an anionic polyelectrolyte formed by alternating molecules of D-glucoronic acid and acetylated glucosamine. In a physiological salt solution this anionic polymer would characteristically interact with cations and water within the solution with concomitant formation of ionic double layers. These interactions would magnify the effect of volume of the hyaluronic acid molecule giving rise to the observed pseudo-plastic behavior. Direct chain to chain interaction at least in concentrated hyaluronic acid solutions appears to play a relatively minor role in the overall viscoelastic behavior of such solutions.
  • pseudo-synovial fluid of the present invention does not create an inflammatory response and closely approximates the properties of human synovial fluid.
  • This pseudo-synovial fluid is prepared as hereinafter set forth from a premium refined grade of sodium carboxymethylcellulose which is widely used in the preparation of foods and is commonly known as cellulose gum.
  • Sodium carboxymethylcellulose has been found to have a close structural resemblance to hyaluronic acid.
  • the sodium carboxymethylcellulose is prepared from natural cellulose and therefore reflects a molecular weight range according to the cellulose source. It is characterized by an average degree of polymerization derived from the range of molecular weight fractions within the raw cellulose. The molecular weight is a major factor controlling the viscosity of aqueous solutions of sodium carboxymethylcellulose.
  • Sodium carboxymethylcellulose is prepared by reacting cellulose swelled with alkali with sodium monochloroacetate. Since each anhydroglucose unit in the cellulose structure has three reactive hydroxyl sites which can react with sodium monochloroacetate, a fully substituted product would have a degree of substitution of three.
  • the degree of substitution is the prime factor effecting water solubility of sodium carboxymethylcellulose. Optimum solubility for most applications occurs at a degree of substitution of about 0.7 which is far below the theoretical maximum.
  • the crystalline regions of cellulose increase the possibility of non-uniform substitution because these regions are not as readily accessible to the reactants as the amorphous regions. Non-uniform substitution causes degrees of thixotropicity of sodium carboxymethylcellulose solutions.
  • the sodium carboxymethylcellulose used was a premium refined grade P75-XH obtained from the Explosive Department of E. I. du Pont de Nemours & Company (Inc).
  • the sodium salt of this grade material constitutes not less than 99.5% of the total product on a dry weight basis.
  • salts normally occurring in the body were added.
  • Such salts were sodium chloride, sodium hydrogen carbonate, potassium chloride and potassium orthophosphate-mono-H.
  • an anti-microbial agent such as methyl parahydroxybenzoate was added. The amounts of the salts used were adjusted to be close to those occurring in blood plasma.
  • the pseudo-synovial fluid is prepared by adding the 500 ml. of distilled water to a mixer, or other suitable stirring device having suflicient liquid capacity such as 1,000 ml. With the mixer operating at high speed the salt ingredients and anti-microbial ingredient were sprinkled into the water and mixing continued for approximately three minutes to assure complete solution. The sodium carboxymethylcellulose was then added by sprinkling slowly into the vortex of the salt solution over a period of three minutes with the mixer still at high speed. A uniform dispersal and solution of the ingredients was thereby obtained. This method produced the most pro nounced pseudo-plastic behavior of the prepared fluid. It should be noted that in the same formulation prepared by adding the sodium carboxymethylcellulose to the water and thereafter adding the anti-microbial and salt ingredients, the fluid produced thereby consistently yielded a product of reduced pseudo-plasticity as compared to the fluid prepared in the preferred manner.
  • the sodium carboxymethylcellulose is used in the range from 0.8 to 1.2 percent (preferably 1.0 percent) by weight and has a Brookfield viscosity in a one percent aqueous solution of at least 2,500 cps. at 25 C.
  • the sodium carboxymethylcellulose is selected to have a distribution of anions along its chain and a molecular weight distribution to provide the desired pseudo-plasticity or viscosity/shear characteristics of the fluid which is being simulated.
  • pseudo-synovial fluid of the present invention efliciently simulates the pseudo-plastic behavior of synovial fluid. It has been subjected to animal tests and was found non-irritating in the anterior chamber of the animals eyes and to knee joint tissue.
  • a similar fluid may be prepared which approximates the aqueous and vitreous humour by increasing the concentration of the sodium carboxymethylcellulose to a concentration within the range from 2 to 4 weight percent.
  • the aqueous humour from animals such as canines and rabbits is approximated by the lower end of such range and then vitreous humour is approximated by the higher end of such range.
  • the simulated human vitreous humour would fall within the range from 2 /2 to 3 /2 weight percent.
  • the present invention has provided an improved pseudo-synovial fluid which closely simulates human synovial fluid and does not have an inflammatory response.
  • the preferred method of preparing such pseudo-synovial fluid has also been clearly disclosed.
  • the method of preparing a synthetic body solution including the steps of mechanically stirring distilled water,
  • said inorganic salts being those salts normally present in blood plasma and being in relatively the same proportion in the resulting synthetic body solutions as in blood plasma, and
  • sodium carboxymethylcellulose having a Brookfield viscosity in an aqueous solution of one percent by weight of at least 2,500 cps. at C.
  • said inorganic salts being those salts normally present in blood plasma and being in relatively the same proportion in the resulting synthetic body solution as in blood plasma, and
  • sodium carboxymethylcellulose having a Brookfield viscosity in an aqueous solution of one percent by weight of at least 2,500 cps. at 25 C.
  • the concentration of said sodium carboxymethylcellulose being in one of the ranges from 0.8 to 1.2 and 2 to 4 weight percent.
  • a synthetic body solution comprising a water solution of sodium carboxymethylcellulose and inorganic salts
  • said inorganic salts being those salts normally present in blood plasma and being in relatively the same proportion as in blood plasma,
  • the resultant concentration of said sodium carboxymethylcellulose being sufficient to provide approximately the physical characteristics of the body solution being simulated and not greater than four percent by weight.
  • a synthetic body solution according to claim 4 in cluding an anti-microbial agent, and said inorganic salts including, sodium chloride, sodium hydrogen carbonate, potassium chloride, and potassium ortho-phosphate mono-H.
  • a pseudo-synovial fluid comprising a water solution of sodium carboxymethylcellulose and inorganic salts
  • said inorganic salts being those salts normally present in blood plasma and being in relatively the same proportion as in blood plasma, said sodium carboxymethylcellulose having a Brookfield viscosity in an aqueous solution of one percent by Weight of at least 2,500 cps. at 25 C.,
  • the resultant concentration of said sodium carboxymethylcellulose being sufficient so that the resultant solution has viscosity and shear rate characteristics whose logarithms are linearly related and approximate the viscosity, shear rate relationship of human synovial fluid.
  • a synthetic body solution comprising a water solution of inorganic salts and sodium carboxymethylcellulose
  • said inorganic salts being those salts normally present in blood plasma and being in relatively the same proportion as in blood plasma,
  • said sodium carboxymethylcellulose having a Brookfield viscosity in an aqueous solution of one percent by weight of at least 2,500 cps. at 25 C.
  • the resultant concentration of said sodium carboxymethylcellulose being sufficient to provide the approximate characteristics of the body solution being simulated and being in one of the ranges from 0.8 to 1.2 and 2 to 4 weight percent.
  • a pseudo-synovial fluid comprising a solution which is the equivalent of the following dissolved in 500 milliliters of distilled Water,

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Inorganic Chemistry (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Medicines Containing Material From Animals Or Micro-Organisms (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicinal Preparation (AREA)
  • Polysaccharides And Polysaccharide Derivatives (AREA)
US00235311A 1972-03-16 1972-03-16 Pseudo-synovial plastic body fluids and method of preparing same Expired - Lifetime US3830910A (en)

Priority Applications (12)

Application Number Priority Date Filing Date Title
US00235311A US3830910A (en) 1972-03-16 1972-03-16 Pseudo-synovial plastic body fluids and method of preparing same
CA165,323A CA1011251A (en) 1972-03-16 1973-03-06 Pseudo-plastic synovial-like body fluids and methods of preparing same
GB1135273A GB1391577A (en) 1972-03-16 1973-03-08 Pseudosynovial plastic body fluids and method of preparing same
IE377/73A IE37384B1 (en) 1972-03-16 1973-03-08 Pseudo-synovial plastic body fluids and method of preparing same
ZA731754A ZA731754B (en) 1972-03-16 1973-03-13 Pseudo-synovial plastic body fluids and method of preparing same
AU53312/73A AU475354B2 (en) 1972-03-16 1973-03-15 Pseudo-synovial plastic body fluids and method of preparing
NL7303596A NL7303596A (enExample) 1972-03-16 1973-03-15
SE7303611A SE425143B (sv) 1972-03-16 1973-03-15 Syntetisk kroppsvetska till anvendning sasom ersettning eller utokning av ledvetska, kammarvatten eller glaskroppen och forfarande for framstellning derav
FR7309303A FR2181824B1 (enExample) 1972-03-16 1973-03-15
JP48030162A JPS49417A (enExample) 1972-03-16 1973-03-16
BE128884A BE796883A (fr) 1972-03-16 1973-03-16 Fluides corporels synthetiques et leur procede de preparation
DE2313221A DE2313221A1 (de) 1972-03-16 1973-03-16 Kuenstliche gelenkschmiere und verfahren zu deren herstellung

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
US00235311A US3830910A (en) 1972-03-16 1972-03-16 Pseudo-synovial plastic body fluids and method of preparing same

Publications (1)

Publication Number Publication Date
US3830910A true US3830910A (en) 1974-08-20

Family

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Family Applications (1)

Application Number Title Priority Date Filing Date
US00235311A Expired - Lifetime US3830910A (en) 1972-03-16 1972-03-16 Pseudo-synovial plastic body fluids and method of preparing same

Country Status (12)

Country Link
US (1) US3830910A (enExample)
JP (1) JPS49417A (enExample)
AU (1) AU475354B2 (enExample)
BE (1) BE796883A (enExample)
CA (1) CA1011251A (enExample)
DE (1) DE2313221A1 (enExample)
FR (1) FR2181824B1 (enExample)
GB (1) GB1391577A (enExample)
IE (1) IE37384B1 (enExample)
NL (1) NL7303596A (enExample)
SE (1) SE425143B (enExample)
ZA (1) ZA731754B (enExample)

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4154822A (en) * 1976-08-02 1979-05-15 The University Of Chicago Polysaccharide for enhancement of cardiac output
US5466680A (en) * 1992-03-26 1995-11-14 Cytologics, Inc. Method and compositions for enhancing white blood cell functioning on a mucosal or cutaneous surface

Families Citing this family (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPH06248023A (ja) * 1993-02-26 1994-09-06 Shinnakamura Kagaku Kogyo Kk 高分子化合物および帯電防止剤
ITMI20091969A1 (it) * 2009-11-11 2011-05-12 Claudia Battaglino Composizione oftalmica
DE102011055683A1 (de) * 2011-11-24 2013-05-29 Götz von Foerster Synthetisches Schmiermittel zur Verwendung als Synovialflüssigkeitsersatz

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4154822A (en) * 1976-08-02 1979-05-15 The University Of Chicago Polysaccharide for enhancement of cardiac output
US5466680A (en) * 1992-03-26 1995-11-14 Cytologics, Inc. Method and compositions for enhancing white blood cell functioning on a mucosal or cutaneous surface

Also Published As

Publication number Publication date
FR2181824A1 (enExample) 1973-12-07
DE2313221A1 (de) 1973-09-20
BE796883A (fr) 1973-07-16
AU475354B2 (en) 1976-08-19
AU5331273A (en) 1974-09-19
GB1391577A (en) 1975-04-23
ZA731754B (en) 1973-12-19
NL7303596A (enExample) 1973-09-18
FR2181824B1 (enExample) 1976-09-03
JPS49417A (enExample) 1974-01-05
IE37384B1 (en) 1977-07-06
CA1011251A (en) 1977-05-31
SE425143B (sv) 1982-09-06
IE37384L (en) 1973-09-16

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Owner name: NOVAMED, INC., HOUSTON, TX, A CORP. OF TX, TEXAS

Free format text: ASSIGNMENT OF ASSIGNORS INTEREST.;ASSIGNORS:HOMSY, CHARLES A.;VITEK, INC., A TX CORP.;REEL/FRAME:005060/0958

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Effective date: 19900522

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