CN111374940A - Collagen injection capable of in-situ polymerization and use method thereof - Google Patents

Collagen injection capable of in-situ polymerization and use method thereof Download PDF

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CN111374940A
CN111374940A CN202010286024.3A CN202010286024A CN111374940A CN 111374940 A CN111374940 A CN 111374940A CN 202010286024 A CN202010286024 A CN 202010286024A CN 111374940 A CN111374940 A CN 111374940A
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collagen
solution
concentration
injection
therapeutic
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冯幸福
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Ningbo Santemuse Biotechnology Co ltd
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    • 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
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/557—Eicosanoids, e.g. leukotrienes or prostaglandins
    • A61K31/5575—Eicosanoids, e.g. leukotrienes or prostaglandins having a cyclopentane, e.g. prostaglandin E2, prostaglandin F2-alpha
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
    • 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
    • A61K47/42—Proteins; Polypeptides; Degradation products thereof; Derivatives thereof, e.g. albumin, gelatin or zein
    • 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
    • A61K47/50—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 the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
    • A61K47/51—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 the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
    • A61K47/62—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 the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being a protein, peptide or polyamino acid
    • A61K47/64—Drug-peptide, drug-protein or drug-polyamino acid conjugates, i.e. the modifying agent being a peptide, protein or polyamino acid which is covalently bonded or complexed to a therapeutically active agent
    • A61K47/6435—Drug-peptide, drug-protein or drug-polyamino acid conjugates, i.e. the modifying agent being a peptide, protein or polyamino acid which is covalently bonded or complexed to a therapeutically active agent the peptide or protein in the drug conjugate being a connective tissue peptide, e.g. collagen, fibronectin or gelatin
    • 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
    • A61P27/00—Drugs for disorders of the senses
    • A61P27/02—Ophthalmic agents
    • A61P27/06—Antiglaucoma agents or miotics

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  • Biomedical Technology (AREA)
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  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
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  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)

Abstract

The invention relates to an in-situ polymerizable collagen injection, which is characterized in that: the injection is a collagen solution containing active components formed by combining therapeutic drugs, proteins and soluble collagen or a collagen solution containing active components formed by combining components with therapeutic action and the soluble collagen, the concentration of the collagen solution is 10mg/ml to 70mg/ml, and the PH is 6.0 to 8.0. The collagen solutions of the invention can be used to deliver any drug, in each case, the therapeutic agent is added to the collagen solution to the desired concentration, and the solution is applied to the appropriate tissue site.

Description

Collagen injection capable of in-situ polymerization and use method thereof
Technical Field
The invention relates to the technical field of in-situ gel, in particular to an in-situ polymerizable collagen injection and a using method thereof.
Background
In the past few years, considerable attention has been paid to the development of in situ gel delivery systems. The in situ polymerized compositions are in solution form prior to administration, which undergoes a gelation or polymerization reaction to form a depot for sustained release of the drug or active ingredient upon administration. These delivery systems have many advantages, including reduced dosing frequency and improved patient compliance and comfort. It is therefore necessary to investigate this technique.
Disclosure of Invention
The present invention has been made in view of the above problems, and provides an in situ polymerizable collagen injection.
In order to solve the technical problems, the invention is realized by the following technical scheme:
the invention relates to an in-situ polymerizable collagen injection, which is characterized in that: the injection is a collagen solution containing active components formed by combining therapeutic drugs, proteins and soluble collagen or a collagen solution containing active components formed by combining components with therapeutic action and the soluble collagen, the concentration of the collagen solution is 10mg/ml to 70mg/ml, and the PH is 6.0 to 8.0.
The invention also provides a use method of the collagen injection capable of in-situ polymerization, which is characterized in that:
1) combining therapeutic agents, proteins, or therapeutic agents with soluble collagen to form a collagen solution containing active ingredients;
2) the collagen solution forms a gel after contacting the tissue, and the active ingredients contained in the solution release the active ingredients at a suitable time point to produce a therapeutic effect after reaching a certain therapeutic concentration.
The invention further provides that: the concentration of the collagen solution is 0.1-10% W/V.
The invention further provides that: the concentration of the collagen solution is 0.5-7.0% W/V.
The invention further provides that: the concentration of the collagen solution is 2.0-5.0% W/V.
The invention further provides that: the concentration of the collagen solution is between 0.1-10% (W/V), and the solution is converted into gel or polymerized into collagen fibril mass within 180 seconds.
The invention further provides that: the concentration of the collagen solution is between 0.5-7.0% (W/V), and the solution is converted into gel or polymerized into collagen fibril mass within 120 seconds.
The invention further provides that: at concentrations between 2-5% (W/V) of the collagen solution, the solution is converted to a gel or polymerized into collagen fibril mass within 90 seconds.
The invention further provides that: the collagen solution is added with fibril components or chemically induces limited cross-linking reaction to increase the cross-linking degree of collagen molecules and increase the anti-degradation capability of the collagen preparation to improve the in vivo stability after injection, and the concentration of the fibril collagen components can be between 0.1 and 2.0 percent (w/v).
The invention further provides that: the chemically cross-linked collagen molecules and the therapeutic agent cross-link collagen amine groups together or to an amine, carboxyl, phenol, sulfonyl or carbohydrate group of the therapeutic agent, and the cross-linking compound comprises a bifunctional acylating agent including an anhydride, acid chloride, sulfonyl chloride.
The collagen solutions of the present invention may be used to deliver any drug, protein or therapeutic agent, including but not limited to drugs for treating glaucoma, growth factors, steroids, antibiotics, angiogenesis inhibitors and cell proliferation inhibitors. In each case, the therapeutic agent is added to the collagen solution to the desired concentration and the solution is applied to the appropriate tissue site. The therapeutic agent may be entrapped in the collagen, or covalently bound and cross-linked to the collagen. Combinations of two or more therapeutic agents may be administered simultaneously, or the therapeutic agents may be combined with other compounds that enhance the effect of the therapeutic agents.
Detailed Description
In order to make the objects, technical solutions and advantages of the embodiments of the present invention more apparent, the technical solutions of the present invention are described clearly and completely below, and it is obvious that the described embodiments are a part of the embodiments of the present invention, not all of the embodiments. All other embodiments, which can be derived by a person skilled in the art from the embodiments given herein without making any creative effort, shall fall within the protection scope of the present invention.
The invention relates to an in-situ polymerizable collagen injection, which is characterized in that: the injection is a collagen solution containing active components formed by combining therapeutic drugs, proteins and soluble collagen or a collagen solution containing active components formed by combining components with therapeutic action and the soluble collagen, the concentration of the collagen solution is 10mg/ml to 70mg/ml, and the PH is 6.0 to 8.0.
The invention also provides a use method of the collagen injection capable of in-situ polymerization, which is characterized in that:
1) combining therapeutic agents, proteins, or therapeutic agents with soluble collagen to form a collagen solution containing active ingredients;
2) the collagen solution forms a gel after contacting the tissue, and the active ingredients contained in the solution release the active ingredients at a suitable time point to produce a therapeutic effect after reaching a certain therapeutic concentration.
The invention further provides that: the concentration of the collagen solution is 0.1-10% W/V.
The invention further provides that: the concentration of the collagen solution is 0.5-7.0% W/V.
The invention further provides that: the concentration of the collagen solution is 2.0-5.0% W/V.
The invention further provides that: the concentration of the collagen solution is between 0.1-10% (W/V), and the solution is converted into gel or polymerized into collagen fibril mass within 180 seconds.
The invention further provides that: the concentration of the collagen solution is between 0.5-7.0% (W/V), and the solution is converted into gel or polymerized into collagen fibril mass within 120 seconds.
The invention further provides that: at concentrations between 2-5% (W/V) of the collagen solution, the solution is converted to a gel or polymerized into collagen fibril mass within 90 seconds.
The invention further provides that: the collagen solution is added with fibril components or chemically induces limited cross-linking reaction to increase the cross-linking degree of collagen molecules and increase the anti-degradation capability of the collagen preparation to improve the in vivo stability after injection, and the concentration of the fibril collagen components can be between 0.1 and 2.0 percent (w/v).
The invention further provides that: the chemically cross-linked collagen molecules and the therapeutic agent cross-link collagen amine groups together or to an amine, carboxyl, phenol, sulfonyl or carbohydrate group of the therapeutic agent, and the cross-linking compound comprises a bifunctional acylating agent including an anhydride, acid chloride, sulfonyl chloride.
The collagen solutions of the present invention may be used to deliver any drug, protein or therapeutic agent, including but not limited to drugs for treating glaucoma, growth factors, steroids, antibiotics, angiogenesis inhibitors and cell proliferation inhibitors. In each case, the therapeutic agent is added to the collagen solution to the desired concentration and the solution is applied to the appropriate tissue site. The therapeutic agent may be entrapped in the collagen, or covalently bound and cross-linked to the collagen. Combinations of two or more therapeutic agents may be administered simultaneously, or the therapeutic agents may be combined with other compounds that enhance the effect of the therapeutic agents.
In particular, the invention is an injectable, in situ polymerizable collagen-based mixture for the sustained delivery of drugs, proteins and other therapeutically useful components. The mixture is transparent, clear and viscous, and can immediately gel and polymerize when contacting with body fluid to form fibrous gel, thereby generating a drug reservoir to achieve the effect of sustained release of effective components.
The present invention describes a method of delivering a therapeutic composition to a site-specific tissue, the method comprising:
1) combining a drug, protein, or therapeutic agent with soluble collagen to form a collagen solution containing an active agent;
2) the collagen solution forms a gel upon contact with tissue, and the active ingredient contained in the solution releases the active ingredient at a suitable point in time to produce a therapeutic effect at a therapeutic concentration.
The absorption time of the collagen composition can be designed to vary from a few hours to a few months. The rate of collagen absorption can be controlled by the form of collagen extracted or prepared, or by the degree of crosslinking of collagen, addition of insoluble collagen and adjustment of collagen concentration. Thus, collagen can be prepared in a variety of forms, or can be chemically modified to obtain a formulation with a desired absorption time, while still maintaining the hydrophilicity and non-immunogenicity of the collagen.
The initial soluble collagen has a low viscosity and can be mixed with drugs, proteins, and therapeutic agents uniformly and administered by injection to a selected tissue site. The rapid polymerization of the collagen vector can realize targeted drug delivery and sustained drug release at specific tissue sites.
Any collagen that is initially soluble and then capable of rapid polymerization (preferably within 180 seconds) can be used in the present invention. The invention is characterized by polymerization upon contact with physiological fluids. A particularly preferred collagen composition for use in the present invention is described in DeVore & Eiferman (U.S. patent No. 5,492,135 assigned to euclidd systems corporation). These collagen compositions are initially soluble and rapidly polymerize upon exposure to physiological fluids in vivo. Such collagen solutions have a concentration of 10mg/ml to over 70mg/ml and a pH of 6.0-8.0.
If desired, the in vivo stability after injection can be improved by increasing the anti-degradation ability of the collagen preparation. This can be achieved by adding fibrillar components to the collagen solution or by increasing the degree of crosslinking of the collagen molecules by chemically inducing a limited crosslinking reaction. The therapeutic agent may also be chemically bound and cross-linked to the collagen, in soluble, partially soluble or intact fibrillar form. Both collagen-collagen crosslinking and therapeutic agent-collagen crosslinking effectively slow the release of the therapeutic agent and thus achieve a sustained release effect.
Any suitable fibrillar component can be utilized to increase the in vivo stability of collagen. The concentration of fibrillar collagen component may be between 0.1-2.0% (w/v).
There are many potential chemical "stabilizing" compounds that can be used to chemically crosslink collagen molecules with therapeutic agents, for example, crosslinking collagen amine groups together or to amine, carboxyl, phenol, sulfonyl or carbohydrate groups of therapeutic agents. Suitable crosslinking compounds include difunctional acylating agents including anhydrides, acid chlorides, sulfonyl chlorides such as 1,2,3, 4-cyclobutanetetracarboxylic dianhydride, 2,3,4, 5-tetracarboxylic dianhydride, 1,2,4, 5-benzenetetracarboxylic dianhydride, ethylenediaminetetraacetic dianhydride, bicyclo (2,2,2) oct-7-ene-2,3,5, 6-tetracarboxylic dianhydride, glutaryl dichloride, adipoyl chloride, 3-methyladipic chloride, pimeloyl chloride, terephthaloyl chloride, resorcinol dichloride, phthaloyl dichloride, 1, 4-phenylenebis (chloroformate), 2, 4-methylenedisulfonyl chloride, 2, 6-naphthalenedisulfonyl chloride, malonyl dichloride, homobifunctional amine crosslinking agents (e.g., homobifunctional imide esters and homobifunctional N-hydroxysuccinimide) and heterobifunctional crosslinking agents (Pierce, rockford, IL).
The collagen therapeutic delivery system is suitable for providing sustained therapeutic action for ocular, otic and nasal treatments, such as sustained release administration of latanoprost for the treatment of glaucoma.
In a preferred embodiment, the administration is by injection and the tissue site is the eye (sclera, vitreous, conjunctiva, infratendinous membrane, retina), ear (cochlea, endolymphatic sac/duct, vestibular labyrinth and all compartments and connecting tubes containing these components), nose (sinus tissue), bone, cartilage, meniscus, tendons, ligaments or dermis.
In other preferred embodiments, the solution is converted to a gel or polymerized into collagen fibril mass within 180 seconds, more preferably within 120 seconds, and most preferably within 90 seconds after injection of the solution. Preferably, the concentration of the collagen-based solution is between 0.1-10%, more preferably between 0.5-7%, most preferably between 2-5% and (w/v).
Furthermore, ideally the collagen-antibiotic drug depot or the collagen-antibiotic-steroid combination depot could be administered continuously after cataract surgery.
By increasing the concentration of collagen to reduce diffusion of the drug, active agent or protein from the gel or fibril mass, the duration of administration of the therapeutic agent can be extended by ionically binding the drug, active agent or protein to the surface. Collagen molecules, or exposing a collagen solution to ultraviolet radiation for a short period of time to induce limited crosslinking.
EXAMPLE 1 preparation of in situ polymerized collagen solution
In situ polymerized collagen was prepared using the method described by DeVore and Eiferman (U.S. Pat. No. 5,492,135; assigned to Euclid systems corporation). Pure soluble type I collagen was purchased from advanced dbiomatrix, inc. Adding sodium chloride to a soluble, pepsin-digested collagen solution (3mg/mL), at a concentration of 0.8M, to precipitate collagen. The white opaque precipitate was recovered by centrifugation at 3500RPM for 30 minutes and concentrated to about 50mg/mL by placing on filter paper. The concentrated collagen precipitate was placed in a dialysis tube with a MW cut-off of 100,000 and dialyzed against 0.1N HCl for 16-18 hours. The resulting clear, viscous, re-dissolved collagen concentrate was then purified using 0.035M EDTA (ethylenediaminetetraacetic acid, disodium dihydrogen disodium salt,
Figure RE-GDA0002499317040000081
) And (6) dialyzing. Dialysis was continued for 5 days, adjusting the pH daily from a starting pH of 4.5 to a final pH of 7.5. The final clear and viscous collagen concentrate was collected and centrifuged to remove air bubbles. The final transparent viscous collagen had a pH of 7.4 and did not fibrillate at room temperature. The pH or temperature does not trigger collagen fibril formation.
Gelation and fibrillation were evaluated. An aliquot of in situ polymerized collagen was injected into 0.8M sodium chloride at 37 c and observed for the presence of gel and fibrillar collagen. The clear viscous collagen solution formed a white, opaque collagen matrix in less than 120 seconds.
Example 2 Long-term sustained Release of Latanoprost from in situ polymerized collagen
Latanoprost was obtained from Sigma-Aldrich. Soluble, pepsin-digested bovine collagen is useful for drug delivery and is available from Advanced Biomatrix. In situ polymerized collagen was prepared by extensive dialysis of salt precipitated collagen with 0.035M EDTA, with a stepwise increase in pH to 7.5. Latanoprost was dissolved in ethanol and added to the polymerized collagen gel to provide a gel depot containing 250 μ g/100 μ L. The gel was incubated in 1.0mL of physiological saline at 37 ℃. All 1.0mL of the solution was removed over a period of 1 to 27 days and replaced with 1.0mL of fresh buffer. The concentration of latanoprost in the buffer aliquots was measured by HPLC analysis (Millennium Research Laboratories).
HPLC analysis showed that initially latanoprost was released in large amounts from the polymer gel, followed by sustained release at an average rate of 1.4 μ g/day. The partially prepolymerized polymeric gel showed a lower initial release followed by a sustained average release rate of 1.68 μ g/day before being placed in the buffer solution. Polymerizing the collagen gel in situ allows the release of latanoprost in vitro to last for more than 30 days.
Example 3 in situ polymerization of collagen Release complement inhibitory peptides
The release behavior of complement inhibitory peptides from collagen polymerized in situ was studied in vitro. The in vitro release was measured for 6 weeks to determine the optimal collagen formulation. The results show biphasic release kinetics, with a first burst over the first 4 days followed by sustained release to 6 weeks.
Finally, it should be noted that: the above-mentioned embodiments are only specific embodiments of the present invention, which are used for illustrating the technical solutions of the present invention and not for limiting the same, and the protection scope of the present invention is not limited thereto, although the present invention is described in detail with reference to the foregoing embodiments, those skilled in the art should understand that: any person skilled in the art can modify or easily conceive the technical solutions described in the foregoing embodiments or equivalent substitutes for some technical features within the technical scope of the present disclosure; such modifications, changes or substitutions do not depart from the spirit and scope of the embodiments of the present invention, and they should be construed as being included therein. Therefore, the protection scope of the present invention shall be subject to the protection scope of the claims.

Claims (10)

1. An in situ polymerizable collagen injection, characterized in that: the injection is a collagen solution containing active components formed by combining therapeutic drugs, proteins and soluble collagen or a collagen solution containing active components formed by combining components with therapeutic action and the soluble collagen, the concentration of the collagen solution is 10mg/ml to 70mg/ml, and the PH is 6.0 to 8.0.
2. A method for using collagen injection capable of in-situ polymerization, which is characterized in that:
1) combining therapeutic agents, proteins, or therapeutic agents with soluble collagen to form a collagen solution containing active ingredients;
2) the collagen solution forms a gel after contacting the tissue, and the active ingredients contained in the solution release the active ingredients at a suitable time point to produce a therapeutic effect after reaching a certain therapeutic concentration.
3. The use of an in situ polymerizable collagen injection according to claim 2, wherein: the concentration of the collagen solution is 0.1-10% W/V.
4. The use of an in situ polymerizable collagen injection according to claim 3, wherein: the concentration of the collagen solution is 0.5-7.0% W/V.
5. The use of an in situ polymerizable collagen injection according to claim 3, wherein: the concentration of the collagen solution is 2.0-5.0% W/V.
6. The use of an in situ polymerizable collagen injection according to claim 3, wherein: the concentration of the collagen solution is between 0.1-10% (W/V), and the solution is converted into gel or polymerized into collagen fibril mass within 180 seconds.
7. The use method of the collagen injection capable of in situ polymerization according to claim 4: the method is characterized in that: the concentration of the collagen solution is between 0.5-7.0% (W/V), and the solution is converted into gel or polymerized into collagen fibril mass within 120 seconds.
8. The use of an in situ polymerizable collagen injection according to claim 5, wherein: at concentrations between 2-5% (W/V) of the collagen solution, the solution is converted to a gel or polymerized into collagen fibril mass within 90 seconds.
9. The use of an in situ polymerizable collagen injection according to claim 6 or 7 or 8, wherein: the collagen solution is added with fibril components or chemically induces limited cross-linking reaction to increase the cross-linking degree of collagen molecules and increase the anti-degradation capability of the collagen preparation to improve the in vivo stability after injection, and the concentration of the fibril collagen components can be between 0.1 and 2.0 percent (w/v).
10. The use of an in situ polymerizable collagen injection according to claim 9: the method is characterized in that: the chemically cross-linked collagen molecules and the therapeutic agent cross-link collagen amine groups together or to an amine, carboxyl, phenol, sulfonyl or carbohydrate group of the therapeutic agent, and the cross-linking compound comprises a bifunctional acylating agent including an anhydride, acid chloride, sulfonyl chloride.
CN202010286024.3A 2020-04-13 2020-04-13 Collagen injection capable of in-situ polymerization and use method thereof Pending CN111374940A (en)

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Citations (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6509031B1 (en) * 1999-11-15 2003-01-21 Board Of Regents, Texas A&M University System System for polymerizing collagen and collagen composites in situ for a tissue compatible wound sealant, delivery vehicle, binding agent and/or chemically modifiable matrix
CN101862455A (en) * 2003-06-26 2010-10-20 普西维达公司 The drug delivery system of in-situ gelling
US20120315265A1 (en) * 2011-06-13 2012-12-13 Chang Gung University Hydrogel-forming polymer, and preparation process and uses thereof
US20130129807A1 (en) * 2010-08-02 2013-05-23 Dale P. DeVore Collagen-based implants for sustained delivery of drugs
US20150111834A1 (en) * 2013-10-18 2015-04-23 Industrial Technology Research Institute Recipe for in-situ gel, and implant, drug delivery system formed thereby
CN104546691A (en) * 2015-01-28 2015-04-29 中国药科大学 Temperature-sensitive in-situ gel preparation composition for anticular injection and preparation method thereof
CN105209005A (en) * 2013-03-04 2015-12-30 德梅尔有限责任公司以埃特诺根有限责任公司名义经营 Injectable in situ polymerizable collagen composition

Patent Citations (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6509031B1 (en) * 1999-11-15 2003-01-21 Board Of Regents, Texas A&M University System System for polymerizing collagen and collagen composites in situ for a tissue compatible wound sealant, delivery vehicle, binding agent and/or chemically modifiable matrix
CN101862455A (en) * 2003-06-26 2010-10-20 普西维达公司 The drug delivery system of in-situ gelling
US20130129807A1 (en) * 2010-08-02 2013-05-23 Dale P. DeVore Collagen-based implants for sustained delivery of drugs
CN103189047A (en) * 2010-08-02 2013-07-03 欧几里得系统公司 Collagen-based implants for sustained delivery of drugs
US20120315265A1 (en) * 2011-06-13 2012-12-13 Chang Gung University Hydrogel-forming polymer, and preparation process and uses thereof
CN105209005A (en) * 2013-03-04 2015-12-30 德梅尔有限责任公司以埃特诺根有限责任公司名义经营 Injectable in situ polymerizable collagen composition
US20150111834A1 (en) * 2013-10-18 2015-04-23 Industrial Technology Research Institute Recipe for in-situ gel, and implant, drug delivery system formed thereby
CN104546691A (en) * 2015-01-28 2015-04-29 中国药科大学 Temperature-sensitive in-situ gel preparation composition for anticular injection and preparation method thereof

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
高春芳等, 上海科学技术出版社 *

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Application publication date: 20200707