CN111214643A - Octreotide composition based on subcutaneous gel sustained release, preparation method and application - Google Patents
Octreotide composition based on subcutaneous gel sustained release, preparation method and application Download PDFInfo
- Publication number
- CN111214643A CN111214643A CN202010168451.1A CN202010168451A CN111214643A CN 111214643 A CN111214643 A CN 111214643A CN 202010168451 A CN202010168451 A CN 202010168451A CN 111214643 A CN111214643 A CN 111214643A
- Authority
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- Prior art keywords
- octreotide
- parts
- thermoplastic polymer
- release
- subcutaneous
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- Pending
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- DEQANNDTNATYII-OULOTJBUSA-N (4r,7s,10s,13r,16s,19r)-10-(4-aminobutyl)-19-[[(2r)-2-amino-3-phenylpropanoyl]amino]-16-benzyl-n-[(2r,3r)-1,3-dihydroxybutan-2-yl]-7-[(1r)-1-hydroxyethyl]-13-(1h-indol-3-ylmethyl)-6,9,12,15,18-pentaoxo-1,2-dithia-5,8,11,14,17-pentazacycloicosane-4-carboxa Chemical compound C([C@@H](N)C(=O)N[C@H]1CSSC[C@H](NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CCCCN)NC(=O)[C@@H](CC=2C3=CC=CC=C3NC=2)NC(=O)[C@H](CC=2C=CC=CC=2)NC1=O)C(=O)N[C@H](CO)[C@H](O)C)C1=CC=CC=C1 DEQANNDTNATYII-OULOTJBUSA-N 0.000 title claims abstract description 56
- 108010016076 Octreotide Proteins 0.000 title claims abstract description 56
- 229960002700 octreotide Drugs 0.000 title claims abstract description 52
- 239000000203 mixture Substances 0.000 title claims abstract description 38
- 238000007920 subcutaneous administration Methods 0.000 title claims abstract description 23
- 238000013268 sustained release Methods 0.000 title claims abstract description 23
- 239000012730 sustained-release form Substances 0.000 title claims abstract description 23
- 238000002360 preparation method Methods 0.000 title abstract description 9
- 229920001169 thermoplastic Polymers 0.000 claims abstract description 21
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 claims abstract description 16
- 239000003960 organic solvent Substances 0.000 claims abstract description 13
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 claims description 20
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 claims description 9
- DZOXUIJDHVERIU-UHFFFAOYSA-N 2-(2-hydroxypropanoyloxy)acetic acid Polymers CC(O)C(=O)OCC(O)=O DZOXUIJDHVERIU-UHFFFAOYSA-N 0.000 claims description 6
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 5
- 238000000034 method Methods 0.000 claims description 5
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims description 4
- 239000007943 implant Substances 0.000 claims description 3
- 229960001494 octreotide acetate Drugs 0.000 claims description 3
- AEMRFAOFKBGASW-UHFFFAOYSA-N Glycolic acid Polymers OCC(O)=O AEMRFAOFKBGASW-UHFFFAOYSA-N 0.000 claims description 2
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 2
- 229920000954 Polyglycolide Polymers 0.000 claims description 2
- 239000012736 aqueous medium Substances 0.000 claims description 2
- 210000001124 body fluid Anatomy 0.000 claims description 2
- 239000010839 body fluid Substances 0.000 claims description 2
- 229920001577 copolymer Polymers 0.000 claims description 2
- 238000002156 mixing Methods 0.000 claims description 2
- 229920000747 poly(lactic acid) Polymers 0.000 claims description 2
- 239000007787 solid Substances 0.000 claims description 2
- 229920001897 terpolymer Polymers 0.000 claims description 2
- 239000003814 drug Substances 0.000 abstract description 9
- 229940079593 drug Drugs 0.000 abstract description 7
- 229920000642 polymer Polymers 0.000 abstract description 4
- 239000000463 material Substances 0.000 abstract description 2
- 238000009472 formulation Methods 0.000 description 9
- 241000700159 Rattus Species 0.000 description 8
- 238000002347 injection Methods 0.000 description 4
- 239000007924 injection Substances 0.000 description 4
- 238000004458 analytical method Methods 0.000 description 3
- 239000008280 blood Substances 0.000 description 3
- 210000004369 blood Anatomy 0.000 description 3
- 238000004007 reversed phase HPLC Methods 0.000 description 3
- XQEJFZYLWPSJOV-XJQYZYIXSA-N acetic acid;(4r,7s,10s,13r,16s,19r)-10-(4-aminobutyl)-19-[[(2r)-2-amino-3-phenylpropanoyl]amino]-16-benzyl-n-[(2r,3r)-1,3-dihydroxybutan-2-yl]-7-[(1r)-1-hydroxyethyl]-13-(1h-indol-3-ylmethyl)-6,9,12,15,18-pentaoxo-1,2-dithia-5,8,11,14,17-pentazacycloicosa Chemical compound CC(O)=O.C([C@@H](N)C(=O)N[C@H]1CSSC[C@H](NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CCCCN)NC(=O)[C@@H](CC=2C3=CC=CC=C3NC=2)NC(=O)[C@H](CC=2C=CC=CC=2)NC1=O)C(=O)N[C@H](CO)[C@H](O)C)C1=CC=CC=C1 XQEJFZYLWPSJOV-XJQYZYIXSA-N 0.000 description 2
- 239000002552 dosage form Substances 0.000 description 2
- 238000004811 liquid chromatography Methods 0.000 description 2
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 2
- 238000004949 mass spectrometry Methods 0.000 description 2
- 239000004005 microsphere Substances 0.000 description 2
- 230000036470 plasma concentration Effects 0.000 description 2
- 229920001606 poly(lactic acid-co-glycolic acid) Polymers 0.000 description 2
- 108700014314 sandostatinLAR Proteins 0.000 description 2
- 238000010254 subcutaneous injection Methods 0.000 description 2
- 239000007929 subcutaneous injection Substances 0.000 description 2
- 230000001225 therapeutic effect Effects 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- 206010000599 Acromegaly Diseases 0.000 description 1
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
- 102000018997 Growth Hormone Human genes 0.000 description 1
- 108010051696 Growth Hormone Proteins 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- 208000009311 VIPoma Diseases 0.000 description 1
- 210000001015 abdomen Anatomy 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 208000002458 carcinoid tumor Diseases 0.000 description 1
- 238000012754 cardiac puncture Methods 0.000 description 1
- 230000007423 decrease Effects 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 230000009969 flowable effect Effects 0.000 description 1
- 238000004108 freeze drying Methods 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 239000000122 growth hormone Substances 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 238000010255 intramuscular injection Methods 0.000 description 1
- 239000007927 intramuscular injection Substances 0.000 description 1
- 230000007794 irritation Effects 0.000 description 1
- 238000010983 kinetics study Methods 0.000 description 1
- 230000001394 metastastic effect Effects 0.000 description 1
- 206010061289 metastatic neoplasm Diseases 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 229920002959 polymer blend Polymers 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 108090000765 processed proteins & peptides Proteins 0.000 description 1
- 239000008213 purified water Substances 0.000 description 1
- 229940072272 sandostatin Drugs 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 230000002459 sustained effect Effects 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/04—Peptides having up to 20 amino acids in a fully defined sequence; Derivatives thereof
- A61K38/08—Peptides having 5 to 11 amino acids
-
- 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
- A61K47/34—Macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyesters, polyamino acids, polysiloxanes, polyphosphazines, copolymers of polyalkylene glycol or poloxamers
-
- 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
- A61K9/0019—Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
- A61K9/0024—Solid, semi-solid or solidifying implants, which are implanted or injected in body tissue
-
- 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
- A61K9/06—Ointments; Bases therefor; Other semi-solid forms, e.g. creams, sticks, gels
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A61P35/04—Antineoplastic agents specific for metastasis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P5/00—Drugs for disorders of the endocrine system
Abstract
The invention discloses an octreotide composition based on subcutaneous gel sustained release, a preparation method and application thereof, wherein the composition comprises the following components in parts by weight: 20-50 parts of thermoplastic polymer, 50-70 parts of biocompatible polar aprotic donor organic solvent and 2-15 parts of octreotide citrate. The octreotide composition prepared by the invention is slowly degraded with the high molecular material after being injected, and the loaded medicine is slowly released into an organism. The drug release rate can be achieved by controlling the molecular weight of the polymer and the drug loading capacity, so that the requirements of doctors and patients can be met in a targeted manner.
Description
Technical Field
The invention belongs to the field of biological pharmacy, and particularly relates to an octreotide composition based on subcutaneous gel sustained release, a preparation method and application thereof.
Background
Octreotide is an artificially synthesized octaamino acid peptide. The main indications for octreotide are in the treatment of acromegaly due to hypersecretion of growth hormone and in the control of metastatic carcinoids and vasoactive intestinal peptide-secreting tumors. The current clinical use is daily subcutaneous injection (Sandostatin, Novartis) or as a one month sustained release intramuscular injection (Sandostatin LAR). The Sandostatin LAR one month dosage form is a microsphere preparation. The drug was encapsulated in a microsphere polymer made of glucose and poly (DL-lactide-glycolide) PLG. The administration mode is very inconvenient and cannot meet the requirements of patients.
Therefore, there is a need for an octreotide composition based on subcutaneous gel sustained release, a preparation method and an application thereof.
Disclosure of Invention
In order to overcome the defects in the prior art, the invention provides an octreotide composition based on subcutaneous gel sustained release, a preparation method and application thereof.
In order to solve the technical problems, the invention provides the following technical scheme:
the invention provides an octreotide composition based on subcutaneous gel sustained release, which comprises the following components in parts by weight: 20-50 parts of thermoplastic polymer, 50-70 parts of biocompatible polar aprotic donor organic solvent and 2-15 parts of octreotide citrate.
In a preferred embodiment of the present invention, the polar aprotic donor organic solvent is one or any combination of N-methyl-2-pyrrolidone, N-dimethylformamide, and dimethylsulfoxide.
In a preferred embodiment of the present invention, the thermoplastic polymer is biodegradable, biocompatible, and totally or mostly insoluble in an aqueous medium or body fluid, and the thermoplastic polymer is one of polylactide, polyglycolide, copolymers thereof, terpolymers thereof, or any combination thereof.
In a preferred embodiment of the present invention, the thermoplastic polymer is a carboxyl terminated 50/50 poly (DL-lactide-glycolide).
In a preferred embodiment of the present invention, the thermoplastic polymer is 75/25 poly (DL-lactide-glycolide) which does not contain terminal carboxyl groups.
In a preferred embodiment of the present invention, the thermoplastic polymer is 85/15 poly (DL-lactide-co-glycolide) which does not contain terminal carboxyl groups.
As a preferred technical scheme of the invention, the average molecular weight of the thermoplastic polymer is 15000-65000.
As a preferable technical scheme of the invention, the octreotide citrate is a mixture of octreotide acetate and citric acid.
As a preferred technical solution of the present invention, the present invention also provides a method for preparing an octreotide composition based on subcutaneous gel sustained release, comprising mixing the following components in any order: 20-50 parts of thermoplastic polymer, 50-70 parts of biocompatible polar aprotic donor organic solvent and 2-15 parts of octreotide citrate.
As a preferred embodiment of the present invention, the present invention further provides a method for administering a subcutaneous gel-based sustained release octreotide composition, comprising injecting a first container containing the composition and a second container containing octreotide citrate, the composition comprising a thermoplastic polymer and a biocompatible polar aprotic donor organic solvent, the first container and the second container being connected injectors, and dispersing the biocompatible polar aprotic donor organic solvent after injection of the components of the first container and the second container to form a solid biodegradable implant comprising an effective amount of the thermoplastic polymer, the polar aprotic donor organic solvent and octreotide citrate.
The octreotide composition based on subcutaneous gel sustained release provided by the invention is a release system for subcutaneous injection, has the volume of about 0.2-0.8 ml, can be used once every month, once every two months, once every three months or once every four months to six months, and is a flowable mixture.
The invention has the beneficial effects that: the octreotide composition prepared by the invention is slowly degraded with the high molecular material after being injected, and the loaded medicine is slowly released into an organism. The drug release rate can be achieved by controlling the molecular weight of the polymer and the drug loading capacity, so that the requirements of doctors and patients can be met in a targeted manner.
Detailed Description
The following description of the preferred embodiments of the present invention is provided for the purpose of illustration and description, and is in no way intended to limit the invention.
Example (b): release kinetics study of octreotide subcutaneous gel preparation in rat
The main objective of this study was to evaluate the 28-day release kinetics of three different gel formulations in rats by liquid chromatography/mass spectrometry (LC/MS) combined method and reversed-phase high performance liquid chromatography (RP-HPLC) with plasma octreotide. Another objective is to collect blood for plasma concentration analysis data of octreotide. The final aim is to evaluate the tissue reaction of the test part and the compatibility of the tested object tissue from a macroscopic view.
In a 28-day study, three subcutaneous gel formulations were tested in 120 male rats, respectively. On day 0, each rat was injected subcutaneously into the abdomen with four gel formulations (about 200 microliters) containing 10 milligrams of octreotide citrate. On days 1, 7, 14, 21, and 28, rats were anesthetized and blood was taken by cardiac puncture. Plasma octreotide was analyzed for blood drug concentrations by a liquid chromatography/mass spectrometry (LC/MS) combination. The subcutaneous residue was removed and subsequently subjected to RP-HPLC analysis to determine its octreotide content. Macroscopic tissue response and compatibility were confirmed by observation of the implant and surrounding tissue.
Test gel dosage forms:
octreotide citrate 10% was suspended in the following different formulations (parts by weight).
The formula I is as follows: 50/50 PLGA: N-methyl-2-pyrrolidone (NMP) ═ 45: 55
And a second formula: 85/15 PLGA: N-methyl-2-pyrrolidone (NMP) ═ 50: 50
And the formula III: 85/15 PLGH: 85/15 PLG: n-methyl-2-pyrrolidone (NMP) ═ 25: 50
Preparation of octreotide citrate:
octreotide acetate 3.5 g was mixed with citric acid 0.66 g (equimolar) and dissolved in 33 ml of purified water. Freeze-drying at-80 deg.C. Weighing 2.4 g of freeze-dried powder and dissolving in 13.5 g of pure water.
Preparing an injector:
the first syringe was filled with 50 mg octreotide citrate.
The second syringe was filled with 560 mg of the gel formulation (thermoplastic polymer + NMP).
Two syringes were connected and octreotide citrate was mixed well with polymer/NMP before injection.
Animal injection:
after anesthetizing the rats, about 200 microliters of the octreotide polymer mixture described above was injected subcutaneously.
TABLE 1 kinetics of octreotide release in rats
TABLE 2 octreotide concentrations in rat plasma
The data show that the first day burst of the tested formulation is low, ranging from 5.5% to 20.6%. The test formulation achieved a stable sustained release of octreotide. Plasma octreotide concentration analysis demonstrated that the formulation could meet the maximum plasma octreotide concentration on the first day and then gradually decline to a relatively steady level. Both drug levels remained above therapeutic plasma levels (0.3 ng/mL). The injection site had slight tissue irritation on day 1 and gradually decreased, continuing to be essentially eliminated by day 21. Studies have shown that the test formulations can provide sustained and stable sustained release of therapeutic levels of octreotide in vivo over a period of one month.
Finally, it should be noted that: although the present invention has been described in detail with reference to the foregoing embodiments, it will be apparent to those skilled in the art that changes may be made in the embodiments and/or equivalents thereof without departing from the spirit and scope of the invention. Any modification, equivalent replacement, or improvement made within the spirit and principle of the present invention should be included in the protection scope of the present invention.
Claims (10)
1. An octreotide composition based on subcutaneous gel sustained release is characterized by comprising the following components in parts by weight: 20-50 parts of thermoplastic polymer, 50-70 parts of biocompatible polar aprotic donor organic solvent and 2-15 parts of octreotide citrate.
2. The subcutaneous gel-based sustained-release octreotide composition according to claim 1, wherein the polar aprotic donor organic solvent is one of N-methyl-2-pyrrolidone, N-dimethylformamide, dimethylsulfoxide, or any combination thereof.
3. The subcutaneous gel-based sustained-release octreotide composition according to claim 1, wherein the thermoplastic polymer is biodegradable, biocompatible, totally or mostly insoluble in aqueous media or body fluids, and is one of polylactide, polyglycolide, copolymers thereof, terpolymers thereof, or any combination thereof.
4. The subcutaneous gel-based sustained-release octreotide composition according to claim 3, wherein the thermoplastic polymer is a carboxyl-terminated 50/50 poly (DL-lactide-glycolide).
5. The subcutaneous gel-based sustained-release octreotide composition according to claim 3, wherein the thermoplastic polymer is 75/25 poly (DL-lactide-glycolide) having no terminal carboxyl groups.
6. The subcutaneous gel-based sustained-release octreotide composition according to claim 3, wherein the thermoplastic polymer is 85/15 poly (DL-lactide-glycolide) having no terminal carboxyl groups.
7. The subcutaneous gel-based sustained-release octreotide composition according to claim 3, wherein the average molecular weight of the thermoplastic polymer is 15000-65000.
8. The octreotide composition based on subcutaneous gel sustained release according to claim 3, wherein octreotide citrate is a mixture of octreotide acetate and citric acid.
9. A method for preparing an octreotide composition based on subcutaneous gel sustained release is characterized by mixing the following components in any order: 20-50 parts of thermoplastic polymer, 50-70 parts of biocompatible polar aprotic donor organic solvent and 2-15 parts of octreotide citrate.
10. A method of administering a subcutaneous gel-based sustained release octreotide composition, comprising injecting a first container containing the composition comprising a thermoplastic polymer and a biocompatible polar aprotic donor organic solvent and a second container containing octreotide citrate, the first and second containers being connected injectors, the components of the first and second containers being injected to disperse the biocompatible polar aprotic donor organic solvent to form a solid biodegradable implant comprising effective amounts of the thermoplastic polymer, the polar aprotic donor organic solvent and octreotide citrate.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202010168451.1A CN111214643A (en) | 2020-03-11 | 2020-03-11 | Octreotide composition based on subcutaneous gel sustained release, preparation method and application |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202010168451.1A CN111214643A (en) | 2020-03-11 | 2020-03-11 | Octreotide composition based on subcutaneous gel sustained release, preparation method and application |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN111214643A true CN111214643A (en) | 2020-06-02 |
Family
ID=70826898
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202010168451.1A Pending CN111214643A (en) | 2020-03-11 | 2020-03-11 | Octreotide composition based on subcutaneous gel sustained release, preparation method and application |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN111214643A (en) |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1474685A (en) * | 2000-09-21 | 2004-02-11 | ������ʵ���ҹ�˾ | Polymeric delivery formulations of leuprolide with improved efficacy |
| CN101193626A (en) * | 2005-03-11 | 2008-06-04 | 益德威士医药股份有限公司 | Controlled release formulations of octreotide |
| US20090092650A1 (en) * | 2004-12-15 | 2009-04-09 | Warren Stephen L | Sustained Delivery Formulations of Octreotide Compounds |
| CN103251929A (en) * | 2005-12-22 | 2013-08-21 | 诺瓦提斯公司 | Sustained release formulation comprising octreotide and two or more polylactide-co-glycolide polymers |
-
2020
- 2020-03-11 CN CN202010168451.1A patent/CN111214643A/en active Pending
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1474685A (en) * | 2000-09-21 | 2004-02-11 | ������ʵ���ҹ�˾ | Polymeric delivery formulations of leuprolide with improved efficacy |
| US20090092650A1 (en) * | 2004-12-15 | 2009-04-09 | Warren Stephen L | Sustained Delivery Formulations of Octreotide Compounds |
| CN101193626A (en) * | 2005-03-11 | 2008-06-04 | 益德威士医药股份有限公司 | Controlled release formulations of octreotide |
| CN103251929A (en) * | 2005-12-22 | 2013-08-21 | 诺瓦提斯公司 | Sustained release formulation comprising octreotide and two or more polylactide-co-glycolide polymers |
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Application publication date: 20200602 |
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