US20050123618A1 - Method of producing micro-capsules for the sustained release of drugs - Google Patents

Method of producing micro-capsules for the sustained release of drugs Download PDF

Info

Publication number
US20050123618A1
US20050123618A1 US11/042,682 US4268205A US2005123618A1 US 20050123618 A1 US20050123618 A1 US 20050123618A1 US 4268205 A US4268205 A US 4268205A US 2005123618 A1 US2005123618 A1 US 2005123618A1
Authority
US
United States
Prior art keywords
microcapsules
producing
citric acid
peptide
acid ester
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.)
Abandoned
Application number
US11/042,682
Inventor
Antonio Parante Duena
Josep Garces Garces
Angel Bonilla Munoz
David Cunillera Colome
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.)
GP Pharm SA
Original Assignee
Lipotec SA
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 Lipotec SA filed Critical Lipotec SA
Publication of US20050123618A1 publication Critical patent/US20050123618A1/en
Priority to US12/148,893 priority Critical patent/US9789064B2/en
Assigned to GP PHARM, S.A. reassignment GP PHARM, S.A. ASSIGNMENT OF ASSIGNORS INTEREST (SEE DOCUMENT FOR DETAILS). Assignors: LIPOTEC, S.A.
Abandoned legal-status Critical Current

Links

Images

Classifications

    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00Medicinal preparations characterised by special physical form
    • A61K9/14Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
    • A61K9/16Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
    • A61K9/1605Excipients; Inactive ingredients
    • A61K9/1629Organic macromolecular compounds
    • A61K9/1641Organic macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyethylene glycol, poloxamers
    • A61K9/1647Polyesters, e.g. poly(lactide-co-glycolide)
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00Medicinal preparations characterised by special physical form
    • A61K9/14Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
    • A61K9/16Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
    • A61K9/1605Excipients; Inactive ingredients
    • A61K9/1617Organic compounds, e.g. phospholipids, fats
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00Medicinal preparations characterised by special physical form
    • A61K9/48Preparations in capsules, e.g. of gelatin, of chocolate
    • A61K9/50Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
    • A61K9/5005Wall or coating material
    • A61K9/5015Organic compounds, e.g. fats, sugars
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00Medicinal preparations characterised by special physical form
    • A61K9/48Preparations in capsules, e.g. of gelatin, of chocolate
    • A61K9/50Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
    • A61K9/5005Wall or coating material
    • A61K9/5021Organic macromolecular compounds
    • A61K9/5031Organic macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyethylene glycol, poly(lactide-co-glycolide)
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P5/00Drugs for disorders of the endocrine system
    • A61P5/02Drugs for disorders of the endocrine system of the hypothalamic hormones, e.g. TRH, GnRH, CRH, GRH, somatostatin
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P5/00Drugs for disorders of the endocrine system
    • A61P5/18Drugs for disorders of the endocrine system of the parathyroid hormones
    • A61P5/22Drugs for disorders of the endocrine system of the parathyroid hormones for decreasing, blocking or antagonising the activity of calcitonin

Definitions

  • the present invention relates to a new type of micro-capsule or micro-bead for the sustained administration of drugs and to a procedure for their preparation.
  • modulating release from microcapsules is understood to mean a reduction in the initial release of encapsulated drug and a release of said drug that is almost linear in time. It is both surprising and unexpected, in view of that described by Pitt et al. that the incorporation of small amounts of citric acid ester into the microcapsule preparation of lactic-co-glycolic polymer that encapsulate a peptide of pharmaceutical interest allows the release of the drug to be almost linear and without the presence of sudden initial releases of the drug.
  • the object of this invention consists of providing pharmaceutical of preparations micro-capsules of polymers of lactic and glycolic acid plastified with small quantities of citric acid esters and which contain peptides.
  • the present invention also comprises the preparation and use of the aforementioned microcapsules.
  • citric acid esters useful for the purposes of the present invention are those normally used as plasticizers for pharmaceutical polymers, such as triethyl citrate, tributyl citrate and acetyl tributyl citrate. Use of triethyl citrate is preferable.
  • micro-capsules can be carried out following any of the methods described in the literature such as, for example, those described in the U.S. Pat. No. 3,773,919.
  • the different procedures for producing micro-capsules of the invention would be grouped into the following sections:
  • a solution of polymer is prepared along with tri-ethyl citrate in a suitable solvent.
  • the drug to be encapsulated is suspended in the polymer and plasticiser solution and a non-solvent of the polymer is added to force deposition of the polymer on the drug crystals. Examples of these procedures without using plasticiser can also be found in documents such as ES 2009346 or EP 052 510.
  • the drug to be encapsulated is dissolved in water or in a solution of some other co-adjuvant in is emulsified in a solution of the polymer and the plasticiser in a suitable solvent such as dichloromethane for example.
  • the resulting emulsion is in turn emulsified in water or in an aqueous solution of an emulsifier such as polyvinylic alcohol.
  • an emulsifier such as polyvinylic alcohol.
  • the drug to be encapsulated, the polymer and the plasticiser are dissolved together in a suitable solvent.
  • This solution is emulsified in water or a solution of an emulsifier such as polyvinyl acid and the organic solvent eliminated by evaporation or extraction.
  • the resulting micro-capsules are recovered by filtration. Examples of these procedures that do not sue the plasticiser can also be found in documents such as U.S. Pat. No. 5,445,832.
  • the drug to be encapsulated, the polymer and the plasticiser are dissolved together in a suitable solvent. This solution is evaporated to dryness and the resulting residue reduced down to a suitable size. Examples of this procedure, although not using the plasticiser, can be also be found in documents such as GB 2,209,937.
  • the citric acid ester is deposited along with the polymer, plastifying it and advantageously modifying the hydrophobicity, flexibility and coating capacity characteristics of the polymer and the release profile of the micro-capsules obtained.
  • micro-capsules are recovered by filtration and dried under vacuum for 48 hours.
  • micro-capsules are recovered by filtration and dried under vacuum for 48 hours.
  • micro-capsules are recovered by filtration and dried under vacuum for 48 hours.
  • micro-capsules containing leuprolide obtained according to example I are weighed into 12 10-ml tubes.
  • Each tube is gently shaken to suspend the micro-capsules in the buffer, the tubes are sealed and placed in an oven at 37° C.

Abstract

Micro-capsules for the slow release of drugs, consisting of a lactic-co-glycolic copolymer to which a plasticiser has been incorporated and which contain a drug of pharmaceutical interested within them.

Description

  • The present invention relates to a new type of micro-capsule or micro-bead for the sustained administration of drugs and to a procedure for their preparation.
  • A large variety of administration systems have been proposed for drugs that require administration over a long time period. The strategy described in the literature as the most successful is that of micro-encapsulation of the drug to administer in a polymer material of the biodegradable and biocompatible polyester type, such as polylactic-co-glycolic (PLGA). There are a large number of bibliographic references to this strategy, such as: U.S. Pat. No. 5,445,832; ES 2009346; CH 661 206; CH 665 558; ES 2037621; U.S. Pat. No. 4,652,441; ES 2020890; U.S. Pat. No. 4,728,721; U.S. Pat. No. 5,330,767; U.S. Pat. No. 4,917,893; U.S. Pat. No. 4,652,441; EP 0 145 240; EP 0 2020 065; EP 0 190 833, among others for example.
  • These polymers have the peculiarity that they are degraded slowly within the body releasing the drug contained inside, and the products of this degradation (lactic acid and glycolic acid) are naturally present within the organism.
  • In the micro-capsules described in the literature of the state of the art it is very hard to achieve a satisfactory modulation of the encapsulated drug release, and to avoid an initial large drug release, as this can only be achieved by changing the composition of the polymer (the ratio of lactic-glycolic acid or the molecular weight thereof), which usually implies making important changes in the procedure for the production of the micro-capsules every time a modification in the drug release profile is desired.
  • In the article published by Pitt et al. in the Journal of Biomedical Materials Research, Vol. 13, pg 497-507, 1979, it is described that tributyl citrate accelerates the release of drugs, for example, progesterone, in microcapsules of polylactic polymers.
  • As a fruit of our research, we have surprisingly discovered that the addition of small amounts of citric acid esters, to the polymer constituting the micro-capsules, allows a very effective modulation of the liberation characteristics of the micro-capsules obtained, without the need to modify the composition of the polymer.
  • In the present specification the term modulating release from microcapsules is understood to mean a reduction in the initial release of encapsulated drug and a release of said drug that is almost linear in time. It is both surprising and unexpected, in view of that described by Pitt et al. that the incorporation of small amounts of citric acid ester into the microcapsule preparation of lactic-co-glycolic polymer that encapsulate a peptide of pharmaceutical interest allows the release of the drug to be almost linear and without the presence of sudden initial releases of the drug.
  • Therefore, the object of this invention consists of providing pharmaceutical of preparations micro-capsules of polymers of lactic and glycolic acid plastified with small quantities of citric acid esters and which contain peptides.
  • The present invention also comprises the preparation and use of the aforementioned microcapsules.
  • The citric acid esters useful for the purposes of the present invention are those normally used as plasticizers for pharmaceutical polymers, such as triethyl citrate, tributyl citrate and acetyl tributyl citrate. Use of triethyl citrate is preferable.
  • By peptides of pharmaceutical interest it is understood:
      • analogues of LHRH such as tryptoreline, leuprolide, gosereline, busereline or cetrorelix
      • analogues of somatostatin such as somatostatin or octreotide
      • analogues of human calcitonin such as salmon calcitonin or carbocalcitonin.
  • The preparation of the micro-capsules can be carried out following any of the methods described in the literature such as, for example, those described in the U.S. Pat. No. 3,773,919. By way of description and without limitation thereto, the different procedures for producing micro-capsules of the invention would be grouped into the following sections:
  • a) Method of Coacervation:
  • A solution of polymer is prepared along with tri-ethyl citrate in a suitable solvent. The drug to be encapsulated is suspended in the polymer and plasticiser solution and a non-solvent of the polymer is added to force deposition of the polymer on the drug crystals. Examples of these procedures without using plasticiser can also be found in documents such as ES 2009346 or EP 052 510.
  • b) Double Emulsion Methods:
  • The drug to be encapsulated is dissolved in water or in a solution of some other co-adjuvant in is emulsified in a solution of the polymer and the plasticiser in a suitable solvent such as dichloromethane for example. The resulting emulsion is in turn emulsified in water or in an aqueous solution of an emulsifier such as polyvinylic alcohol. Once this second emulsion has been carried out the solvent in which the polymer was dissolved is eliminated through evaporation or extraction. The resulting micro-capsules are obtained directly by filtration. Examples of these procedures that do not use the plasticiser can also be found in documents such as U.S. Pat. No. 4,652,441.
  • c) Simple Emulsion Method:
  • The drug to be encapsulated, the polymer and the plasticiser are dissolved together in a suitable solvent. This solution is emulsified in water or a solution of an emulsifier such as polyvinyl acid and the organic solvent eliminated by evaporation or extraction. The resulting micro-capsules are recovered by filtration. Examples of these procedures that do not sue the plasticiser can also be found in documents such as U.S. Pat. No. 5,445,832.
  • d) Methods of Solvent Evaporation:
  • The drug to be encapsulated, the polymer and the plasticiser are dissolved together in a suitable solvent. This solution is evaporated to dryness and the resulting residue reduced down to a suitable size. Examples of this procedure, although not using the plasticiser, can be also be found in documents such as GB 2,209,937.
  • In the present invention, in all cases, the citric acid ester is deposited along with the polymer, plastifying it and advantageously modifying the hydrophobicity, flexibility and coating capacity characteristics of the polymer and the release profile of the micro-capsules obtained.
  • This is reducing the initial release of the encapsulated drug and making this release almost linear in time.
  • The present invention is now described by means of following, non-limiting examples:
  • EXAMPLE 1
  • Production of micro-capsules, containing leuprolide acetate, which presents a drug release profile suitable for one month.
  • 3 g of tri-ethyl citrate and 1.45 g of lactic-co-glycolic polymer (mw=50000 with monomer ratio of 1/1) are dissolved in 50 ml of dichloromethane. When the polymer is fully dissolved 67 mg of leuprolide acetate are added and then suspended by sonication.
  • 63 g of silicone of 350 cts is added slowly with intensive stirring. And when all the silicone has been added the content of the reactor is poured onto 2.5 1 of n-heptane and stirred for 1 hour.
  • The micro-capsules are recovered by filtration and dried under vacuum for 48 hours.
  • EXAMPLE 2
  • Production of micro-capsules with one-month release containing octreotide acetate.
  • 2 g of tri-ethyl citrate and 1.45 g of lactic-co-glycolic polymer (mw=50000 with monomer ratio of 1/1) are dissolved in 50 ml of dichloromethane. When the polymer is fully dissolved 67 mg of octreotide acetate are added and then suspended by sonication.
  • 70 g of silicone of 350 cts is added slowly with intensive stirring. And when all the silicone has been added the content of the reactor is poured onto 2.5 1 of n-heptane and stirred for 1 hour.
  • The micro-capsules are recovered by filtration and dried under vacuum for 48 hours.
  • EXAMPLE 3
  • Production of micro-capsules with a three-month release profile containing Triptoreline acetate.
  • 2 g of tri-ethyl citrate and 1.45 g of lactic-co-glycolic polymer (mw=50000 with monomer ratio of 1/1) are dissolved in 50 ml of dichloromethane. When the polymer is fully dissolved 45 mg of triptoreline acetate are added and then suspended by sonication.
  • 70 g of silicone of 350 cts is added slowly with intensive stirring. And when all the silicone has been added the content of the reactor is poured onto 2.5 1 of heptane and stirred for 1 hour.
  • The micro-capsules are recovered by filtration and dried under vacuum for 48 hours.
  • EXAMPLE 4
  • In vitro determination of the drug release by the micro-capsules obtained. MATERIAL NEEDED:
  • 12 plastic 10-ml tubes with lid.
  • 1 rack for tubes.
  • Procedure:
  • Approximately 10 mg of micro-capsules containing leuprolide obtained according to example I are weighed into 12 10-ml tubes.
  • To each tube 2 ml of phosphate buffer 1/30 M and pH=7.0 are added.
  • Each tube is gently shaken to suspend the micro-capsules in the buffer, the tubes are sealed and placed in an oven at 37° C.
  • Taking samples for the control of the hydrolysis is carried out in accordance with the following table:
    TABLE 1
    Taking samples for analysis of leuprolide released.
    Time Tube no. Type of analysis
    1 h 1, 2 Supernatant
    3 h 3 Supernatant
    6 h 4 Supernatant
    1 d 5 and 6 Pellet
    2 d 7 Pellet
    4 d 8 Pellet
    Point Tube no. Type of analysis
     8 d 10 Pellet
    11 d 1 and 11 Pellet
    14 d 2 Pellet
    18 d 3 and 12 Pellet
    23 d 9 Pellet
    29 d 4 and 5 Pellet
  • The analysis of leuprolide released is carried out by HPLC in the following conditions:

Claims (14)

1-11. (canceled)
12. A method for producing microcapsules which comprises the steps of:
a) dissolving a lactic co-glycolic copolymer and a citric acid ester derivative in a solvent in which said lactic co-glycolic copolymer and said citric acid ester derivative are soluble to form a solution;
b) adding a peptide of pharmaceutical interest to the solution to form a peptide suspension in said solution;
c) adding an alkyl derivative to the solution to produce deposition of the lactic co-glycolic copolymer and the citric acid ester derivative on the peptide;
d) adding the suspension obtained in step (c) to a solution in which said lactic co-glycolic copolymer and citric acid ester are not soluble to harden and precipitate microcapsules thus formed; and
e) isolating the microcapsules thus formed;
wherein said citric acid ester derivative is added in an amount sufficient to regulate the release rate of said peptide of pharmaceutical interest from said microcapsules once said microcapsules are within the body of a subject.
13. The method for producing microcapsules according to claim 12, wherein the citric acid ester used in forming said microcapsules is selected from triethyl citrate, tributyl citrate and acetyl tributyl citrate.
14. The method for producing microcapsules according to claim 13, wherein the citric acid ester used in forming said microcapsules is triethyl citrate.
15. The method for producing microcapsules according to claim 14, wherein the amount of said triethyl citrate is between 0.1% and 60% by weight of the copolymer.
16. The method for producing microcapsules according to claim 12, wherein the ratio between lactate and glycolate units n the lactic co-glycolic copolymer is between 100:0 and 10:90, both inclusive.
17. The method for producing microcapsules according to claim 16, wherein said alkyl derivative is silicon oil.
18. The method for producing microcapsules according to claim 12, wherein the peptide of pharmaceutical interest encapsulated within said microcapsules is an analogue of LHRH.
19. The method for producing microcapsules according to claim 18, wherein the analogue of LHRH encapsulated within said microcapsules is selected from tryptoreline, leuprolide, gosereline, busereline and cetrorelix.
20. The method for producing microcapsules according to claim 12, wherein the peptide of pharmaceutical interest encapsulated within said microcapsules is somatostatine or an analogue thereof.
21. The method for producing microcapsules according to claim 20, wherein the analogue of somatostatine encapsulated within said microcapsules is octreotide.
22. The method for producing microcapsules according to claim 12, wherein the peptide of pharmaceutical interest encapsulated within said microcapsules is analogue of human calcitonine.
23. The method for producing microcapsules according to claim 22, wherein the analogue of human calcitonin encapsulated within said microcapsules is salmon calcitonine or carbocalcitonine
24. A pharmaceutical composition comprising microcapsules prepared according to claim 12 and a pharmaceutically acceptable carrier.
US11/042,682 1999-12-17 2005-01-25 Method of producing micro-capsules for the sustained release of drugs Abandoned US20050123618A1 (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
US12/148,893 US9789064B2 (en) 1999-12-17 2008-04-23 Method for delivering a peptide to a subject at a modulated rate via microcapsules of lactic-co-glycolic copolymer containing said peptide

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
ES9902768 1999-12-17
ES009902768A ES2169980B1 (en) 1999-12-17 1999-12-17 MICROCAPSULES FOR THE PROLONGED RELEASE OF PHARMACOS.

Related Parent Applications (3)

Application Number Title Priority Date Filing Date
US09913671 Division 2000-12-15
US09/913,671 Division US20020187196A1 (en) 1999-12-17 2000-12-15 Micro-capsules for the sustained release of drugs
PCT/ES2000/000475 Division WO2001043724A1 (en) 1999-12-17 2000-12-15 Microcapsules for sustained release of drugs

Related Child Applications (1)

Application Number Title Priority Date Filing Date
US12/148,893 Division US9789064B2 (en) 1999-12-17 2008-04-23 Method for delivering a peptide to a subject at a modulated rate via microcapsules of lactic-co-glycolic copolymer containing said peptide

Publications (1)

Publication Number Publication Date
US20050123618A1 true US20050123618A1 (en) 2005-06-09

Family

ID=8310957

Family Applications (3)

Application Number Title Priority Date Filing Date
US09/913,671 Abandoned US20020187196A1 (en) 1999-12-17 2000-12-15 Micro-capsules for the sustained release of drugs
US11/042,682 Abandoned US20050123618A1 (en) 1999-12-17 2005-01-25 Method of producing micro-capsules for the sustained release of drugs
US12/148,893 Expired - Fee Related US9789064B2 (en) 1999-12-17 2008-04-23 Method for delivering a peptide to a subject at a modulated rate via microcapsules of lactic-co-glycolic copolymer containing said peptide

Family Applications Before (1)

Application Number Title Priority Date Filing Date
US09/913,671 Abandoned US20020187196A1 (en) 1999-12-17 2000-12-15 Micro-capsules for the sustained release of drugs

Family Applications After (1)

Application Number Title Priority Date Filing Date
US12/148,893 Expired - Fee Related US9789064B2 (en) 1999-12-17 2008-04-23 Method for delivering a peptide to a subject at a modulated rate via microcapsules of lactic-co-glycolic copolymer containing said peptide

Country Status (13)

Country Link
US (3) US20020187196A1 (en)
EP (1) EP1151746B1 (en)
JP (1) JP5021880B2 (en)
AT (1) ATE234608T1 (en)
AU (1) AU774680B2 (en)
BR (1) BRPI0008197B8 (en)
CA (1) CA2362769C (en)
DE (1) DE60001717T2 (en)
DK (1) DK1151746T3 (en)
ES (2) ES2169980B1 (en)
MX (1) MXPA01008348A (en)
PT (1) PT1151746E (en)
WO (1) WO2001043724A1 (en)

Families Citing this family (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20040097419A1 (en) * 2002-11-19 2004-05-20 Holger Petersen Organic compounds
US20090110744A1 (en) * 2005-03-01 2009-04-30 Sun Pharma Advanced Research Company Limited Sustained release pharmaceutical compositions
EP2359809B1 (en) * 2005-12-22 2019-08-14 Novartis AG Sustained release formulation comprising octreotide and two or more polylactide-co-glycolide polymers
ES2324009B1 (en) * 2007-11-23 2010-05-21 Gp Pharm S.A. PHARMACEUTICAL COMPOSITION OF SUSTAINED RELEASE OF SOMATOSTATINE OR AN ANALOG OF HIS.
CN105267153B (en) * 2015-11-27 2018-05-11 上海苏豪逸明制药有限公司 A kind of Triptorelin sustained-release microparticle and preparation method thereof
CN110954491B (en) * 2019-12-09 2022-11-15 北京博恩特药业有限公司 Method for measuring in-vitro dissolution rate of goserelin acetate sustained-release implant
JP7371519B2 (en) 2020-02-14 2023-10-31 村田機械株式会社 Automatic warehouse

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4954298A (en) * 1985-02-07 1990-09-04 Takeda Chemical Industries, Ltd. Method for producing microcapsule
US5538739A (en) * 1989-07-07 1996-07-23 Sandoz Ltd. Sustained release formulations of water soluble peptides

Family Cites Families (21)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US2151185A (en) 1936-01-16 1939-03-21 Carbide & Carbon Chem Corp Esters of glycol monoesters and acylated hydroxy acids
US3773919A (en) 1969-10-23 1973-11-20 Du Pont Polylactide-drug mixtures
EP0052610A1 (en) 1980-05-29 1982-06-02 NICKLAUS, Helen Carol Stringed musical instrument teaching device and process
GB2132887A (en) * 1982-11-15 1984-07-18 Procter & Gamble Enteric-coated anti-inflammatory compositions
CH661206A5 (en) 1983-09-23 1987-07-15 Debiopharm Sa PROCESS FOR THE PREPARATION OF A MEDICINAL PRODUCT FOR THE TREATMENT OF HORMONDEPENDENT DISEASES.
JPS60100516A (en) 1983-11-04 1985-06-04 Takeda Chem Ind Ltd Preparation of sustained release microcapsule
JP2551756B2 (en) 1985-05-07 1996-11-06 武田薬品工業株式会社 Polyoxycarboxylic acid ester and method for producing the same
CH665558A5 (en) 1985-10-09 1988-05-31 Debiopharm Sa Phase sepn. prodn. of microcapsules for water soluble pharmaceuticals - using fluoro-substd. aliphatic hydrocarbon as non-solvent in the hardening stage
GB2209937B (en) 1987-09-21 1991-07-03 Depiopharm S A Water insoluble polypeptides
CH679207A5 (en) 1989-07-28 1992-01-15 Debiopharm Sa
IT1243390B (en) 1990-11-22 1994-06-10 Vectorpharma Int PHARMACEUTICAL COMPOSITIONS IN THE FORM OF PARTICLES SUITABLE FOR THE CONTROLLED RELEASE OF PHARMACOLOGICALLY ACTIVE SUBSTANCES AND PROCEDURE FOR THEIR PREPARATION.
SE9100610D0 (en) * 1991-03-04 1991-03-04 Procordia Ortech Ab BIORESORBABLE MATERIAL FOR MEDICAL USE
CH683149A5 (en) * 1991-07-22 1994-01-31 Debio Rech Pharma Sa Process for the preparation of microspheres of a biodegradable polymeric material.
US5518730A (en) 1992-06-03 1996-05-21 Fuisz Technologies Ltd. Biodegradable controlled release flash flow melt-spun delivery system
EP0644756A4 (en) 1993-03-15 1996-02-28 Univ Michigan System for controlled release of antiarrhythmic agents.
EP0858772B1 (en) 1995-10-05 2008-10-29 Kabushiki Kaisha Toshiba X-ray imaging apparatus
SE505146C2 (en) * 1995-10-19 1997-06-30 Biogram Ab Particles for delayed release
DE19545257A1 (en) * 1995-11-24 1997-06-19 Schering Ag Process for the production of morphologically uniform microcapsules and microcapsules produced by this process
WO1998041190A1 (en) * 1997-03-18 1998-09-24 Sunstar Inc. Composition for forming solid particles
GB9718986D0 (en) * 1997-09-09 1997-11-12 Danbiosyst Uk Controlled release microsphere delivery system
US6818018B1 (en) * 1998-08-14 2004-11-16 Incept Llc In situ polymerizable hydrogels

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4954298A (en) * 1985-02-07 1990-09-04 Takeda Chemical Industries, Ltd. Method for producing microcapsule
US5538739A (en) * 1989-07-07 1996-07-23 Sandoz Ltd. Sustained release formulations of water soluble peptides

Also Published As

Publication number Publication date
EP1151746A1 (en) 2001-11-07
DK1151746T3 (en) 2003-07-21
US20020187196A1 (en) 2002-12-12
JP5021880B2 (en) 2012-09-12
ATE234608T1 (en) 2003-04-15
EP1151746B1 (en) 2003-03-19
ES2194793T3 (en) 2003-12-01
ES2169980B1 (en) 2003-11-01
BRPI0008197B8 (en) 2021-05-25
BR0008197A (en) 2002-01-22
JP2003516960A (en) 2003-05-20
BRPI0008197B1 (en) 2017-05-09
ES2169980A1 (en) 2002-07-16
AU2173501A (en) 2001-06-25
DE60001717T2 (en) 2004-03-18
CA2362769A1 (en) 2001-06-21
CA2362769C (en) 2008-09-09
PT1151746E (en) 2003-07-31
WO2001043724A1 (en) 2001-06-21
MXPA01008348A (en) 2004-03-19
US9789064B2 (en) 2017-10-17
US20080233198A1 (en) 2008-09-25
DE60001717D1 (en) 2003-04-24
AU774680B2 (en) 2004-07-01

Similar Documents

Publication Publication Date Title
US9789064B2 (en) Method for delivering a peptide to a subject at a modulated rate via microcapsules of lactic-co-glycolic copolymer containing said peptide
KR100482262B1 (en) Sustained-release particles
US5503851A (en) Microencapsulation of water-soluble medicaments
Kumar Nano and microparticles as controlled drug delivery devices
CA2127317C (en) Method of producing sustained-release preparation
CA2036089C (en) Prolonged release microcapsules
EP1328258B1 (en) A controlled-release, parenterally administrable microparticle preparation
DE69631824T2 (en) BIODEGRADABLE NANOPARTICLES WITH CONTROLLED RELEASE OF INSULIN
US5643607A (en) Prolonged release microcapsules
US6630156B1 (en) Process for preparing biodegradable microspheres containing physiologically active agents
HU211602A9 (en) Sustained release formulations of water soluble peptides
AU2001294458B2 (en) Biodegradable microparticles for controlled release administration, with purified amylopectin-based starch of reduced molecular weight
JPH0713023B2 (en) Pharmaceutical composition for maintaining and controlling drug release over a long period of time
US5635216A (en) Microparticle compositions containing peptides, and methods for the preparation thereof
TW200836770A (en) Controlled release system and manufacture method thereof
KR100202073B1 (en) Microencapsulated sustained-release preparation and manufacturing method thereof
JP2716747B2 (en) Polyester-based drug composition for controlling drug release
JP4308933B2 (en) Microsphere formulation containing dolastatin 10 derivative
CN1463696A (en) Biological active control release microsphere and method for preparing same
NL195089C (en) Preparations of water-soluble peptides with a slow release.
XIAOHUA Controlled release alginate-based microparticulate systems for drug delivery and chemoembolization

Legal Events

Date Code Title Description
STCB Information on status: application discontinuation

Free format text: ABANDONED -- FAILURE TO RESPOND TO AN OFFICE ACTION

AS Assignment

Owner name: GP PHARM, S.A., SPAIN

Free format text: ASSIGNMENT OF ASSIGNORS INTEREST;ASSIGNOR:LIPOTEC, S.A.;REEL/FRAME:028554/0529

Effective date: 20120712