US3911098A - Medicament carrier - Google Patents

Medicament carrier Download PDF

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Publication number
US3911098A
US3911098A US441695A US44169574A US3911098A US 3911098 A US3911098 A US 3911098A US 441695 A US441695 A US 441695A US 44169574 A US44169574 A US 44169574A US 3911098 A US3911098 A US 3911098A
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US
United States
Prior art keywords
eye
poly
glucosamine
acetyl
drug
Prior art date
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Expired - Lifetime
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US441695A
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English (en)
Inventor
Richard Carl Capozza
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.)
Wyeth Holdings LLC
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American Cyanamid Co
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Filing date
Publication date
Application filed by American Cyanamid Co filed Critical American Cyanamid Co
Priority to US441695A priority Critical patent/US3911098A/en
Priority to AR257455A priority patent/AR206618A1/es
Priority to ZA00750472A priority patent/ZA75472B/xx
Priority to IL46496A priority patent/IL46496A/xx
Priority to AU77602/75A priority patent/AU492714B2/en
Priority to GB4193/75A priority patent/GB1499751A/en
Priority to PH16765A priority patent/PH13485A/en
Priority to NL7501365A priority patent/NL7501365A/xx
Priority to IT48048/75A priority patent/IT1036866B/it
Priority to DE19752505305 priority patent/DE2505305A1/de
Priority to CA219,603A priority patent/CA1045975A/en
Priority to SE7501464A priority patent/SE7501464L/
Priority to BE153217A priority patent/BE825367A/xx
Priority to RO7581371A priority patent/RO68711A/ro
Priority to PL17794875A priority patent/PL177948A1/xx
Priority to ES434618A priority patent/ES434618A1/es
Priority to FR7504245A priority patent/FR2260356B1/fr
Priority to DD184115A priority patent/DD118801A5/xx
Priority to CS75860A priority patent/CS207808B1/cs
Priority to JP50016958A priority patent/JPS50123815A/ja
Application granted granted Critical
Publication of US3911098A publication Critical patent/US3911098A/en
Anticipated expiration legal-status Critical
Expired - Lifetime 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
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
    • A61K47/36—Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/0048—Eye, e.g. artificial tears
    • A61K9/0051—Ocular inserts, ocular implants
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/20—Pills, tablets, discs, rods
    • A61K9/2004—Excipients; Inactive ingredients
    • A61K9/2022—Organic macromolecular compounds
    • A61K9/205—Polysaccharides, e.g. alginate, gums; Cyclodextrin

Definitions

  • the time of release of medicaments or drugs can be in part controlled by incorporating the drugs in a matrix of an enzymatically degradable form of poly(N-acetyl-D-glucosamine) so that said form is slowly enzymatically degraded over a period of time by body fluids and the drug is released into the body fluids at the time of use for a longer period than the drug would be released without the matrix carrier.
  • OSMOTIC FLUID RESER- VOIR FOR OSMOTICALLY ACTIVATED LONG- TERM CONTINUOUS INJECTOR DEVICE osmotic pressure is used to propel a piston system so that a drug is slowly injected.
  • Example l4 discloses a bioerodible ocular insert containing pilocarpine free base using a matrix of polyglycolic acid. Pilocarpine is mixed with polyvinyl alcohol and used as a core between two sheets of polyglycolic acid. (see page I 12). Page discloses polyesters of lactic and glycolic acid as a carrier.
  • Page 73, line ll mentions chitin among other polysaccharides and plant hydrocolloids. Presumably, the reference is to the naturally occurring form of chitin.
  • Claim 5 is drawn to bioerodibility by enzymatic cleavage.
  • Claim 14 is drawn to cross-linked gelatin.
  • Claim 50 is drawn to polylactic 0r polyglycolic release rate controlling materials.
  • Carboxymethylchitin is disclosed in Carbohyd. Res. 7, 483-485 (1968), Ralph Trujillo.
  • Chitin has been estimated to be the second most abundant polysaccharide in nature with a synthesis in the neighborhood of a billion tons a year by marine organisms. See Chitin, N. V. Tracey, Reviews of Pure and Applied Chemistry, Royal Australian Chemical Institute, Vol. 7, No. l, March I957, pages I to l4.
  • PAG poly( N-acetyl-D-glucosamine) sometimes herein abbreviated as PAG
  • PAG poly( N-acetyl-D-glucosamine)
  • the enzyme lysozyme is particularly effective in the enzymatic degradation of the biodegradable forms of PAG.
  • Various forms of PAG may have different degradation rates, and the degradation rate may vary with the location of the drug release device.
  • an ocular insert may be designed to be placed adjacent to the eyeball inside the eyelid, in the cul-desac of the conjunctiva between the schlera of the eyeball and the lid.
  • An insert needs to be soft so that it will cause a minimum of irritation to the eyeball and the degradation products are preferably such that they may be washed away by the flow of tears without the necessity for removal of the device after its drug content has been delivered.
  • chitin is used herein to refer to the various although ll l5 be lmdel'smod that the device in naturally occurring forms of chitin including the promany form ay b0 used n Other lOCflllOHS tein and inorganic carbonate components.
  • N-acetyl-D-glucosamine ha he form purified chitin is used to refer to chitin after purifica- 6 tion to remove calcium carbonate and other inorganic H OH salts and various proteins which may be present and is K essentially poly(N-acetyl-D-glucosamine).
  • H used as a name for poly( N-acctyl-D-glucosamine) with- H 1 out specifying whether it is a naturally occurring material containing inorganic salts and proteins or whether H 3 E the term is intended to designate purified poly(N-acetu 5 yl-D'glucosamine) without specifying the degree of pu- O rity or the character of the impurities present.
  • poly( N- acctyl-D-glucosamine) refers both to the purified poly( N-acetyl-D-glucosamine) from chitin itself as well as the carboxymethyl, hydroxyethyl, and O-ethyl derivatives, etc.
  • the carboxymethyl derivative properly called poly[- N-acetyl-6-O-( carboxymethyl )-D-glucosamine] has the formula a, 0011 COOH NHAc NHAc v cH 00H coon
  • the hydroxyethyl derivative, properly called poly[N- Groups below the plane of the paper are shown by a y y y y g has thc dotted bondv formula H OCH CH OH HQ NHAC l I W o I 0 We cm ocH 0H, OH
  • P0ly(N-acetyl-D-glucosamine) has ascribed to it the The O-ethyl derivative. properly called poly-[N- formula (ring hydrogens omitted for clarity) acetyl-G-O-(ethyl)-D-glucosamine] has the formula 6 (3H. OH
  • carboxymethylation, hydroxyethylation, or ethylation may not be l71 and may in part occur on the 3-hydroxyl.
  • under or over-substitution of the poly[ N-acetyl-6-0-( carboxymethyl )-D-glucosamine] is to be included as a biodegradable form of PAS.
  • the solubility in a specified solvent is one test of the degree of substitution.
  • the ()-ethyl derivative is water soluble when the ethyl group to glucosamine ratio is about i and organic soluble when the degree of substitution is greater than 1.
  • drug is used to refer to a substance other than a food intended to affect the structure or function of the body of man or other animal.
  • the term is some what broader than medicine in that the term medicine" is sometimes considered to be restricted to an agent which is administered to affect or control a pathogenic condition.
  • the broader term drug here is also used to include steroids and other fertility controlling agents which may be incorporated in an intrauterine contraceptive device or other materials which may be included to affect the fertility of females or males either as an intrauterine device or subcutaneously.
  • dispensing is used to designate a method of administering a drug to man or other animal and includes the release of the drug to a desired location.
  • the release over a prolonged period of time designates any decrease in the release rate of the drug over that which would be expected if the drug were administered alone and would include from the matter of a few minutes as, for example, in an ocular insert containing pilocarpine to a duration of six months to a year which might be desired for the administration of a steroid in an intrauterine contraceptive device.
  • a longer period of administration such as the lifetime of the patient, could be desired but usually a period of a very few hours up to about six months includes the medically preferred range.
  • the enzymatically degradable form of poly-(N-acetyl-D-glucosamine) is a solid which can be removed, a longacting repository pellet for insertion beneath the skin is quite practical as if for any medical reason it is desired to discontinue administration of the drug, the insert with the remaining drug charge may be removed simply by excision.
  • enzymatically degradable refers to a form of poly( N-acetyl-D-glucosamine) or its derivatives which is broken down into body fluid soluble components and which are washed out as in tears, or transported elsewhere by tears, or other body fluid, and later degraded further or metabolized by the body or excreted by the body.
  • the problem of retention by the body or disposal of the residual matrix is minimal or non-existent.
  • Lysozyme occurs in practically all of the body fluids, particularly the tears, and effectively breaks down the polymer chain to water soluble or disposable components.
  • Chitosan which is a common name for the deacylated form of poly(N-acetyl-D-glucosamine), and which is poly(D-glucosamine) is not enzymatically degradable by lysozyme.
  • poly( N-acetyl-D-glucosamine) are not readily hydrolyzed by water.
  • I in a phosphate buffer at pH 7.2 at 37C for 24 hours is not hydrolyzed whereas under the same time and temperature in the presence of lysozyme hydrolysis occurs,
  • any of the drugs used to treat the eye and surrounding tissues can be incorporated with the enzymatically degradable form of PAG of this invention.
  • drugs which will pass through the eye or the tissue surrounding the eye to the bloodstream, but which are not used in therapy of the eye itself can be incorporated in the enzymatically degradable PAG matrix.
  • Suitable drugs for use in therapy of the eye with the present insert include, without limitation: Antiinfectives: such as antibiotics, including tetracycline, chlortetracycline, bacitracin, neomycin, polymyxin, gramicidin, oxytetracycline, chloramphenicol, and erythromycin; sulfonamides, including sulfacetamide, sulfamethazole, and sulfisoxazole; antivirals, including idoxuridine; and other anti-infectives including nitrofurazone and sodium propionate; Antiallergenics such as antazoline, methapyrilene, chlorpheniramine, pyrilamine and prophenpyridamine; Anti-inflammatories such as hydrocortisone, hydrocortisone acetate, dexamethasone, triamcinolone, medrysone, prednisolone, prednisolone 2l-phosphate and prednisol
  • Decongestants such as phenylephrine, naphazoline, and tetrahydrazoline', Miotics and anticholinesterases such as pilocarpine, eserine salicylate, carbachol, disopropyl fluorophosphate, phospholine iodide, and demecarium bromide; matropine, scopolamine, tropicamide, eucatropine, and hydroxyamphetamine and sympathominetics such as epinephrine.
  • Miotics and anticholinesterases such as pilocarpine, eserine salicylate, carbachol, disopropyl fluorophosphate, phospholine iodide, and demecarium bromide
  • matropine, scopolamine, tropicamide, eucatropine, and hydroxyamphetamine and sympathominetics such as epinephrine.
  • Drugs can be in various forms, such as unchanged molecules, components of molecular complexes, or nonir ritating, pharmacologically acceptable salts, such as hydrochloride, hydrobromide, sulfate, phosphate, nitrate, borate, acetate, maleate, tartrate, salicylate, etc. Furthermore. simple derivatives of the drugs (such as ethers, esters.
  • the amount of drug incorporated in the ocular insert varies widely, depending on the particular drug, the desired therapeutic effect, and the time span for which the ocular insert will be used. Since the ocular insert is intended to provide the complete dosage regime for eye therapy for but a particular time span, such as 24 hours, there is no critical upper limit on the amount of drug incorporated in the device. The lower limit will depend on the activity of the drug and its capability of being released from the device. Thus, it is not practical to define a range for the therapeutically effective amount of drug incorporated into the device. However, typically, from I mi crogram to l milligram of drug is incorporated in each insert.
  • the polymeric material used to form the ocular insert is chosen for its compatibility with a particular drug and its capability of releasing that drug at an appropriate rate over a prolonged period of time.
  • specific, but nonlimiting, examples of combinations of drugs and polymers for use in forming the ocular insert include: poly- N-acetyl-6-O-(carboxymethyl )-D- glucosamine] and epinephrine; poly[N-acetyl-6-0- (carboxymethyl)-D-glucosamine] and mixture of pilocarpine hydrochloride and epiniphrine; poly[Nacetyl- 64H 2 '-hydroxyethyl )-D-glucosamine] and acetazolamide; poly[N-acetyl-b-(J-(ethyl)'D-glucosamine] and phospholine iodide; poly[N-acetyl-fi-(carboxymethyl)-D-glucos
  • the degradation rate of the enzymatically degradable form of poly(N-acetyl-D-glucosamine) can be lowered by cross-linking, if a slower release rate is preferred.
  • the ocular insert can be fabricated in any convenient shape for comfortable retention in the cul-de-sac. It is important. however, that the device have no sharp, jagged. or rough edges which can irritate the sensitive tissues of the eye.
  • the marginal outline of the ocular insert can be ellipsoidal, bean-shaped, rectangular, etc. in cross section, it can be concavo-convex, rectangular, etc.
  • the ocular insert is flexible and, in use, will assume essentially the configuration of the seleral curvature, the original shape of the device is not of controlling importance. Dimensions of the device can vary widely.
  • the lower limit on the size of the device is governed by the amount of the particular drug to be applied to the eye and surrounding tissues to elicit the de sired pharmacological response, as well as by the smallest sized device which conveniently can be inserted and removed from the eye.
  • the upper limit on the size of the device is governed by the limited space within the cul de-sac that conveniently and comfortably can be filled with an ocular insert.
  • the ocular insert is 4 to millimeters in length, l to 12 millimeters in width, and 0.l to l millimeter in thickness.
  • it is ellipsoidal in shape and about 6 X 4 X 0.5 millimeters in size.
  • the matrix containing the drug of the present invention can include other drugs for other areas.
  • a tablet of a size and shape adapted to being swallowed is preferred.
  • a tablet or rod such that it may be placed under the skin in an appropriate location is selected. The amount of drug and the time over which it is to be dispensed are controlling in the choice of size of the implant.
  • the drug may be combined with the enzymatically degradable form of PAG matrix in any convenient way, it is particularly convenient to dissolve both in a common solvent which permits casting of the enzymatically degradable form of PAG as a matrix containing the drug to be dispersed therein.
  • HIPA hexafluoroisopropanol
  • HFAS hexafluoroacetone sesquihydrate
  • N-acetyl-6-()-( carboxymethyl )-D- glucosamine], l, poly[N-acetyl-(J-O-(2'-hydroxyethyl) D-glucosamine], ll, and poly[N-acetyl-6-O (ethyl J-D- glucosamine], III, are preferred because of cosolubility with many drugs in common solvents, including water. Non-toxic solvents are preferred.
  • l and II are water soluble at the 5% level, and III is water soluble at the 5% level if the degree of substitution is not more than about 1, and organic solvent soluble if more than about 1.
  • Organic solvents may be used such as alcohols, chloroform, benzene, toluene, mix tures of benzene and toluene with alcohols and l e tones.
  • Pilocarpine or other drugs can be incorporated into matrices of these enzymatically degradable forms of PAG by hydrogen bonding, covalent bonding, ionic bonding or simple entrapment.
  • the matrices themselves can be variably crosslinked with a variety of physical and chemical agents. They can be sterilized and when hydrated become quite pliable, while retaining adequate strength to resist manipulation.
  • EXAMPLE V1 Poly( N-Acetyl-D-Glucosamine) Matrix Membranes of poly(N-acetyl-D-glucosamine) were prepared by dissolving poly(N-acetyl-D-glucosamine) in each of hexafluoroacetone sesquihydrate (1.4% solution) and hexafluoroisopropanol (2% solution).
  • the films were tough, transparent, non-tacky, flexible and were quite pliable when hydrated yet retained adequate strength to resist manipulation.
  • the membranes showed no hydrolysis after exposure to water for 5 days. In the presence of lysozyme, however, the films were degraded slowly. The films eroded release any drug in the film slowly.
  • the autoclave was purged several times with nitrogen and 53.2 ml. of ethylene oxide was added (16 equivalents/equivalent of FAQ). The mixture was held at 50C. for 18 hours. The solution was then carefully neutralized with glacial acetic acid, dialyzed and then lyophilized.
  • the hydroxyethyl derivative can be further purified by precipitating the polymer from aqueous solution with acetone.
  • a freshly precipitated sample of poly[N- acetyl-6-0-(2'-hydroxyethyl)-D-glucosamine] readily dissolved in water. 5% aqueous sodium hydroxide, and 3% acetic acid and is precipitated from these solutions by acetone.
  • Samples analyzed for C, H and N showed the composition to be one in which 1.5 hydroxyethyl groups had been substituted per glucosamine residue.
  • the ethylchloride was mixed with benzene (75% of the amount of ethylchloride).
  • the reaction time was 10 hours and the temperature was controlled as follows: 1 hour heating up to 60C.. 1 hour heating up to 80C., 1 hour heating up to lC. and 7 hours at 130C.
  • An organic solvent soluble product was obtained.
  • the following solvents are useful for solubilization (5% solution) of this polymer at room temperature: 0-xylene. benzene,
  • toluene methylethyl ketone. 1.4 mixture of alcohol and benzene. chlorofomi and alcohols.
  • the drug is bound ionically to the polymer.
  • the attractive features of such a system are l slower drug delivery and (2) capability of delivering piloearpine as a free base which. as such. has a higher potency.
  • piloearpine as the free base since it is unstable in this form and as a result is 0 usually delivered as the hydrochloride or nitrate salt.
  • Effective medication for a treatment day is obtained by placing an insert 1 mm by l0 mm in the human eye.
  • a method of dispensing an eye drug over a pro longed period of time comprising inserting in the conjunctival sac of the eye a bioerodible enzymatically cleavable occular insert which is shaped to conform to the curvature of the eye and is adapted for insertion and retention in the conjunctival sac of the eye of an eye drug intimately dispersed in an uncoated matrix directly contacting the conjunctival sac of the eye of an enzymatically degradable form of poly( N-acetyl-D- glucosamine) selected from the group consisting of poly[ N-acetyl-6-O-(carboxymethyl )-D-glucosamine poly[ N-acetyl-6-0-( 2'-hydroxyethyl )-D-glucosamine, and poly[ N-acetyl-6-0-( ethyl )-D-glucosamine whereby the said form of poly(N-acetyl-
  • An enzymatically degradable bioerodible eye drug delivery occular insert device which is shaped to conform to the eye and is adapted for insertion and retention in the conjunctival sac of the eye for administering an eye drug to the eye of a living mammal comprising: an uncoated matrix adapted to directly contact the conjunctival sac of the eye consisting essentially of an enzymatically degradable form of poly(N-aeetyl-D- glucosamine) selected from the group consisting of poly[ N-acetyl6-O-( carboxymethyl )'D-glucosamine poly[ N-acetyl-6-0-( 2 '-hydroxyethyl )-D-glucosamine 1.
  • a method for dispensing a free base form of an eye drug over a prolonged period of time comprising inserting in the conjunctiva] sac of the eye a bioerodible enzymatically cleavable oecular insert which is shaped to conform to the curvatuve of the eye and is adapted for insertion and retention in the conjunctival sac of the eye of the free base form of an eye drug intimately dispersed in and ionically bound to an enzymatically degradable form of poly[N-acetyl-6-()-(carhoxymethyl)- D-glucosamine], whereby the said poly[N-acetyl-6-()- carboxymethyl)-D-glucosamine] is slowly enzymatibase form of an at least slightly water soluble eye drug.

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Epidemiology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Inorganic Chemistry (AREA)
  • Ophthalmology & Optometry (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicinal Preparation (AREA)
  • Saccharide Compounds (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
US441695A 1974-02-11 1974-02-11 Medicament carrier Expired - Lifetime US3911098A (en)

Priority Applications (20)

Application Number Priority Date Filing Date Title
US441695A US3911098A (en) 1974-02-11 1974-02-11 Medicament carrier
AR257455A AR206618A1 (es) 1974-02-11 1975-01-01 Agente enzimaticamente degradable biodesgastable util como vehiculo para suministrar una droga levemente soluble en agua
ZA00750472A ZA75472B (en) 1974-02-11 1975-01-22 Medicament carrier
IL46496A IL46496A (en) 1974-02-11 1975-01-23 Enzymatic degradable ocular device comprising poly (n-acetyld-glucosamine) as medicament carrier
AU77602/75A AU492714B2 (en) 1975-01-24 Medicament carrier
GB4193/75A GB1499751A (en) 1974-02-11 1975-01-30 Pharmaceutical preparation
PH16765A PH13485A (en) 1974-02-11 1975-01-31 Medicament carrier
NL7501365A NL7501365A (nl) 1974-02-11 1975-02-05 Werkwijze voor het regelen van de vertraagde te van een geneesmiddel.
IT48048/75A IT1036866B (it) 1974-02-11 1975-02-06 Composizione per la erogazione controllata di me dicamenti
CA219,603A CA1045975A (en) 1974-02-11 1975-02-07 Enzyme degradable medicament carriers
DE19752505305 DE2505305A1 (de) 1974-02-11 1975-02-07 Enzymatisch abbaubarer bioerodierbarer arzneimitteltraeger
BE153217A BE825367A (fr) 1974-02-11 1975-02-10 Matrice de medicament pour liberation progressive
RO7581371A RO68711A (ro) 1974-02-11 1975-02-10 Procedeu de conditionare a unor medicamente oftalmologice
PL17794875A PL177948A1 (en) 1974-02-11 1975-02-10 Sposob wytwarzania enzymatycznie rozkladalnych ulegajacych bioerozji lekow
SE7501464A SE7501464L (enrdf_load_stackoverflow) 1974-02-11 1975-02-10
ES434618A ES434618A1 (es) 1974-02-11 1975-02-11 Procedimiento para la preparacion de dispositivos de sumi- nistro de drogas biorresionales, enzimaticamente degrada- bles.
FR7504245A FR2260356B1 (enrdf_load_stackoverflow) 1974-02-11 1975-02-11
DD184115A DD118801A5 (enrdf_load_stackoverflow) 1974-02-11 1975-02-11
CS75860A CS207808B1 (en) 1974-02-11 1975-02-11 Matrix
JP50016958A JPS50123815A (enrdf_load_stackoverflow) 1974-02-11 1975-02-12

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US441695A US3911098A (en) 1974-02-11 1974-02-11 Medicament carrier

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US3911098A true US3911098A (en) 1975-10-07

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US441695A Expired - Lifetime US3911098A (en) 1974-02-11 1974-02-11 Medicament carrier

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US (1) US3911098A (enrdf_load_stackoverflow)
JP (1) JPS50123815A (enrdf_load_stackoverflow)
AR (1) AR206618A1 (enrdf_load_stackoverflow)
BE (1) BE825367A (enrdf_load_stackoverflow)
CA (1) CA1045975A (enrdf_load_stackoverflow)
CS (1) CS207808B1 (enrdf_load_stackoverflow)
DD (1) DD118801A5 (enrdf_load_stackoverflow)
DE (1) DE2505305A1 (enrdf_load_stackoverflow)
ES (1) ES434618A1 (enrdf_load_stackoverflow)
FR (1) FR2260356B1 (enrdf_load_stackoverflow)
GB (1) GB1499751A (enrdf_load_stackoverflow)
IL (1) IL46496A (enrdf_load_stackoverflow)
IT (1) IT1036866B (enrdf_load_stackoverflow)
NL (1) NL7501365A (enrdf_load_stackoverflow)
PH (1) PH13485A (enrdf_load_stackoverflow)
PL (1) PL177948A1 (enrdf_load_stackoverflow)
RO (1) RO68711A (enrdf_load_stackoverflow)
SE (1) SE7501464L (enrdf_load_stackoverflow)
ZA (1) ZA75472B (enrdf_load_stackoverflow)

Cited By (16)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4066747A (en) * 1976-04-08 1978-01-03 Alza Corporation Polymeric orthoesters housing beneficial drug for controlled release therefrom
US4287175A (en) * 1978-06-22 1981-09-01 Merck & Co., Inc. Contact lens wetting agents
US4343787A (en) * 1975-07-29 1982-08-10 Merck & Co., Inc. Shaped ophthalmic inserts for treating dry eye syndrome
EP0136013A3 (en) * 1983-08-08 1986-02-12 Unitika Ltd. Method for manufacture of biodegradable drug donor and drug donor made thereby
EP0159139A3 (en) * 1984-03-16 1987-02-04 Unitika Ltd. Method for preparation of a shaped chitin body containing a physiologically active substance
US5277900A (en) * 1982-08-07 1994-01-11 Henkel Kommanditgesellschaft Auf Aktien Method for blood coagulation on hard tissues
US5290752A (en) * 1984-03-16 1994-03-01 Unitika Ltd. Method for preparation of a shaped chitin body containing a physiologically active substance
US5741329A (en) * 1994-12-21 1998-04-21 Board Of Regents, The University Of Texas System Method of controlling the pH in the vicinity of biodegradable implants
US6065476A (en) * 1994-12-21 2000-05-23 Board Of Regents, University Of Texas System Method of enhancing surface porosity of biodegradable implants
US20030225381A1 (en) * 2002-05-30 2003-12-04 Van Dalen Johan T.W. Apparatus and method for delivering controlled quantities of one or more agents to the eye
US6767899B1 (en) 2000-08-29 2004-07-27 Leiner Health Services Corp. Composition and method for treatment of conditions having an inflammatory component
US20070156248A1 (en) * 2005-03-01 2007-07-05 Doron Marco Bioerodible self-deployable intragastric implants
US20110015666A1 (en) * 2005-03-01 2011-01-20 Tulip Medical Ltd. Bioerodible self-deployable intragastric implants
US9320645B2 (en) 2013-05-29 2016-04-26 Terry Glasser Approach to administering ocular medication
US10507127B2 (en) 2012-06-07 2019-12-17 Epitomee Medical Ltd. Expandable device
US11129793B2 (en) 2013-12-05 2021-09-28 Epitomee Medical Ltd Retentive devices and systems for in-situ release of pharmaceutical active agents

Families Citing this family (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4221779A (en) * 1977-06-28 1980-09-09 Graham Neil B Pharmaceutical composition for treating tropical diseases
JPS57134412A (en) * 1981-02-12 1982-08-19 Unitika Ltd Biodegradable drug donor
EP0086627B1 (en) * 1982-02-12 1985-08-28 Unitika Ltd. Anti-cancer device
JPS62193638A (ja) * 1986-02-20 1987-08-25 Kao Corp 顆粒剤
US4931551A (en) * 1988-07-05 1990-06-05 University Of Delaware Dispersions of chitin and product therefrom
WO1993004732A1 (en) 1991-09-09 1993-03-18 The Government Of The United States Of America, As Represented By The Secretary Department Of Health And Human Services Methods and devices for treating hemophilia and aids
US5383873A (en) * 1992-12-09 1995-01-24 Regents Of The University Of Minnesota Smooth muscle chemical pacemaker

Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US2040879A (en) * 1934-06-21 1936-05-19 Du Pont Substantially undegraded deacetylated chitin and process for producing the same
US2040880A (en) * 1934-06-21 1936-05-19 Du Pont Process for the preparation of films and filaments and products thereof
US2168374A (en) * 1936-07-09 1939-08-08 Visking Corp Chemical compounds and products produced therefrom
US3632754A (en) * 1968-02-12 1972-01-04 Lescarden Ltd Use of chitin for promoting wound healing
US3736646A (en) * 1971-10-18 1973-06-05 American Cyanamid Co Method of attaching surgical needles to multifilament polyglycolic acid absorbable sutures
US3845201A (en) * 1972-04-24 1974-10-29 S Loucas Solid state ophthalmic medication delivery method

Patent Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US2040879A (en) * 1934-06-21 1936-05-19 Du Pont Substantially undegraded deacetylated chitin and process for producing the same
US2040880A (en) * 1934-06-21 1936-05-19 Du Pont Process for the preparation of films and filaments and products thereof
US2168374A (en) * 1936-07-09 1939-08-08 Visking Corp Chemical compounds and products produced therefrom
US3632754A (en) * 1968-02-12 1972-01-04 Lescarden Ltd Use of chitin for promoting wound healing
US3736646A (en) * 1971-10-18 1973-06-05 American Cyanamid Co Method of attaching surgical needles to multifilament polyglycolic acid absorbable sutures
US3845201A (en) * 1972-04-24 1974-10-29 S Loucas Solid state ophthalmic medication delivery method

Cited By (29)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4343787A (en) * 1975-07-29 1982-08-10 Merck & Co., Inc. Shaped ophthalmic inserts for treating dry eye syndrome
US4066747A (en) * 1976-04-08 1978-01-03 Alza Corporation Polymeric orthoesters housing beneficial drug for controlled release therefrom
US4287175A (en) * 1978-06-22 1981-09-01 Merck & Co., Inc. Contact lens wetting agents
US5277900A (en) * 1982-08-07 1994-01-11 Henkel Kommanditgesellschaft Auf Aktien Method for blood coagulation on hard tissues
EP0136013A3 (en) * 1983-08-08 1986-02-12 Unitika Ltd. Method for manufacture of biodegradable drug donor and drug donor made thereby
US4704268A (en) * 1983-08-08 1987-11-03 Unitika Ltd. Method for manufacture of biodegradable drug donor and drug donor made thereby
EP0159139A3 (en) * 1984-03-16 1987-02-04 Unitika Ltd. Method for preparation of a shaped chitin body containing a physiologically active substance
US5290752A (en) * 1984-03-16 1994-03-01 Unitika Ltd. Method for preparation of a shaped chitin body containing a physiologically active substance
US5741329A (en) * 1994-12-21 1998-04-21 Board Of Regents, The University Of Texas System Method of controlling the pH in the vicinity of biodegradable implants
US6065476A (en) * 1994-12-21 2000-05-23 Board Of Regents, University Of Texas System Method of enhancing surface porosity of biodegradable implants
US6767899B1 (en) 2000-08-29 2004-07-27 Leiner Health Services Corp. Composition and method for treatment of conditions having an inflammatory component
US20040234599A1 (en) * 2000-08-29 2004-11-25 Leiner Health Services Corp. Composition and method for maintaining healthy mobile joints and cartilage
US7338942B2 (en) 2000-08-29 2008-03-04 Leiner Health Services, Corp. Composition and method for maintaining healthy mobile joints and cartilage
US20030225381A1 (en) * 2002-05-30 2003-12-04 Van Dalen Johan T.W. Apparatus and method for delivering controlled quantities of one or more agents to the eye
US7018646B2 (en) 2002-05-30 2006-03-28 Van Dalen Johan T W Apparatus and method for delivering controlled quantities of one or more agents to the eye
US20070156248A1 (en) * 2005-03-01 2007-07-05 Doron Marco Bioerodible self-deployable intragastric implants
US8845673B2 (en) 2005-03-01 2014-09-30 Tulip Medical Ltd. Bioerodible self-deployable intragastric implants and methods for use thereof
US20110015666A1 (en) * 2005-03-01 2011-01-20 Tulip Medical Ltd. Bioerodible self-deployable intragastric implants
US20110015665A1 (en) * 2005-03-01 2011-01-20 Tulip Medical Ltd. Bioerodible self-deployable intragastric implants
US20110022072A1 (en) * 2005-03-01 2011-01-27 Tulip Medical Ltd. Bioerodible self-deployable intragastric implants
US20110040318A1 (en) * 2005-03-01 2011-02-17 Tulip Medical Ltd. Bioerodible self-deployable intragastric implants
US8267888B2 (en) 2005-03-01 2012-09-18 Tulip Medical Ltd. Bioerodible self-deployable intragastric implants
US7699863B2 (en) * 2005-03-01 2010-04-20 Tulip Medical Ltd. Bioerodible self-deployable intragastric implants
US8858496B2 (en) 2005-03-01 2014-10-14 Tulip Medical Ltd. Bioerodible self-deployable intragastric implants
US8864784B2 (en) 2005-03-01 2014-10-21 Tulip Medical Ltd. Bioerodible self-deployable intragastric implants
US10507127B2 (en) 2012-06-07 2019-12-17 Epitomee Medical Ltd. Expandable device
US11712356B2 (en) 2012-06-07 2023-08-01 Epitomee Medical Ltd Expanded device
US9320645B2 (en) 2013-05-29 2016-04-26 Terry Glasser Approach to administering ocular medication
US11129793B2 (en) 2013-12-05 2021-09-28 Epitomee Medical Ltd Retentive devices and systems for in-situ release of pharmaceutical active agents

Also Published As

Publication number Publication date
JPS50123815A (enrdf_load_stackoverflow) 1975-09-29
AU7760275A (en) 1976-07-29
ZA75472B (en) 1976-01-28
SE7501464L (enrdf_load_stackoverflow) 1975-08-12
CS207808B1 (en) 1981-08-31
AR206618A1 (es) 1976-08-06
FR2260356B1 (enrdf_load_stackoverflow) 1978-07-28
PH13485A (en) 1980-05-21
FR2260356A1 (enrdf_load_stackoverflow) 1975-09-05
PL177948A1 (en) 1978-04-10
BE825367A (fr) 1975-08-11
GB1499751A (en) 1978-02-01
IL46496A (en) 1978-08-31
NL7501365A (nl) 1975-08-13
RO68711A (ro) 1980-10-30
DE2505305A1 (de) 1975-08-21
CA1045975A (en) 1979-01-09
ES434618A1 (es) 1977-04-16
IT1036866B (it) 1979-10-30
DD118801A5 (enrdf_load_stackoverflow) 1976-03-20
IL46496A0 (en) 1975-06-25

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