# US 11,998,665 B2 · Biodegradable ureteral stents, methods and uses thereof

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- Number: US 11,998,665 B2
- Document ID: US11998665B2
- Status: Granted
- Kind: B2
- Application number: 16/084,059
- Filed: 2017-03-13
- Published: 2020-07-23
- Granted: 2024-06-04
- Earliest claimed: 2016-03-11
- Assignees: Association for the Advancement of Tissue Engineering Cell Based Technologies & Therapies (A4Tec)—AssociaçãO
- Applicants: Association for the Advancement of Tissue Engineering and Cell Based Technologies & Therapies (A4Tec)
- Inventors: Rui Luis Gonçalves Dos Reis; Ana Rita Cruz Duarte; Alexandre António Antunes Barros; Estêvão Augusto Rodrigues De Lima; Carlos André Ribeiro Oliveira
- Web page: https://patentgrep.com/patent/US11998665B2

## CPC

- A61L 31/10: Macromolecular materials
- A61L 31/148: {Materials at least partially resorbable by the body}
- A61F 2/04: Hollow or tubular parts of organs, e.g. bladders, tracheae, bronchi or bile ducts (A61F2/18, A61F2/20 take precedence; instruments specially adapted for placement or removal of stents or stent-grafts A61F2/95)
- A61K 31/337: having four-membered rings, e.g. taxol
- A61K 31/704: attached to a condensed carbocyclic ring system, e.g. sennosides, thiocolchicosides, escin, daunorubicin {(digitoxin A61K31/7048)}
- A61K 31/7068: having oxo groups directly attached to the pyrimidine ring, e.g. cytidine, cytidylic acid
- A61K 47/36: Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
- A61K 47/42: Proteins; Polypeptides; Degradation products thereof; Derivatives thereof, e.g. albumin, gelatin or zein (oligopeptides having up to five amino acids {A61K47/183}; polyamino acids A61K47/34)
- A61L 31/041: {Mixtures of macromolecular compounds}
- A61L 31/042: {Polysaccharides}
- A61L 31/045: {Gelatin}
- A61L 31/16: Biologically active materials, e.g. therapeutic substances {(A61L31/047 takes precedence)}
- A61L 31/18: Materials at least partially X-ray or laser opaque
- A61P 13/00: Drugs for disorders of the urinary system
- A61P 35/00: Antineoplastic agents
- A61P 43/00: Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- C08L 83/06: containing silicon bound to oxygen-containing groups (C08L83/12 takes precedence)
- A61F 2002/048: {Ureters}
- A61L 2300/416: Anti-neoplastic or anti-proliferative or anti-restenosis or anti-angiogenic agents, e.g. paclitaxel, sirolimus
- A61L: METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES (preservation of bodies or disinfecting characterised by the agents employed A01N; preserving, e.g. sterilising, food or foodstuffs A23; preparations for medical, dental or toiletry purposes A61K)
- A61F: FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS (dental prosthetics A61C)
- A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- C08L: COMPOSITIONS OF MACROMOLECULAR COMPOUNDS (compositions based on polymerisable monomers C08F, C08G; artificial filaments or fibres D01F; textile treating compositions D06)

## Abstract

The present disclosure relates to biodegradable ureteral stents comprising an anti-cancer drug, and to a composition for use in medicine that may be used to ensure patency of a channel, namely a mammal ureter, for example, an obstructed ureter by a urinary stone, neoplasia or by a surgical procedure. The biodegradable ureteral stents (BUS) disclosed in the present disclosure unexpectedly allow a proper release of anti-cancer drugs, thus extending the duration of the treatment and increasing the efficacy of the treatment.

## Claims

### Claim 1

A stent comprising a polymeric substrate, wherein the polymeric substrate comprises:
10-50% (w/w) of alginate;
45-85% (w/w) of gelatine;
3-50% (w/w) a polymeric biodegradable resin for coating said polymeric substrate; and
no more than 10% (w/w) of an anti-cancer drug;
wherein at least one anti-cancer drug is selected from the list consisting of paclitaxel, epirubicin, doxorubicin, gemcitabine, and mixtures thereof.

### Claim 2 (depends on 1)

The stent according to claim 1, comprising no more than 5% (w/w) of the anti-cancer drug.

### Claim 3 (depends on 1)

The stent according to claim 1, wherein the anti-cancer drug comprises a mixture of anti-cancer drugs, wherein the mixture is: paclitaxel and epirubicin; or paclitaxel and doxorubicin; or paclitaxel and gemcitabine; or epirubicin and doxorubicin; or epirubicin and gemcitabine; or doxorubicin and gemcitabine; or paclitaxel, epirubicin and doxorubicina; or epirubicin, doxorubicina and gemcitabine; or paclitaxel, epirubicin and gemcitabine.

### Claim 4 (depends on 1)

The stent according to claim 1, wherein the polymeric substrate comprises 20-40% (w/w) of alginate and 55-70% (w/w) of gelatine.

### Claim 5 (depends on 1)

The stent according to claim 1, further comprising a contrast agent.

### Claim 6 (depends on 5)

The stent according to claim 5, comprising:
2-5% (w/w) of the contrast agent, wherein the polymeric substrate comprises 20-40% (w/w) of alginate and 55-70% (w/w) of gelatine.

### Claim 7 (depends on 1)

The stent according to claim 1, further comprising:
5% (w/w) of a contrast agent, wherein the polymeric substrate comprises 30% (w/w) of alginate and 65% (w/w) of gelatine.

### Claim 8 (depends on 1)

The stent according to claim 1, wherein said resin is selected from the group consisting of: polycaprolactone resin, polyglycolide and its copolymers, poly(lactic-co-glycolic acid) with lactic acid, poly(glycolide-co-caprolactone) with ε-caprolactone, and poly (glycolide-co-trimethylene carbonate) with trimethylene carbonate, or mixtures of the foregoing.

### Claim 9 (depends on 1)

The stent according to claim 1, further comprising contrast agent is selected from the group consisting of: barium salts, bismuth salts, spinel pigments, or mixtures of the foregoing.

### Claim 10 (depends on 1)

The stent according to claim 1, further comprising a crosslinking agent.

### Claim 11 (depends on 10)

The stent according to claim 10, further comprising a crosslinking agent is selected from the ionic crosslinking agents, including ionic crosslinking agents having monovalent or divalent ions, from which:
the cation is selected from the group consisting of: calcium, magnesium, barium, strontium, boron, beryllium, aluminium, iron, copper, cobalt, lead, silver, or mixtures of the foregoing;
the anion is selected from the group consisting of: chloride, nitrate, phosphate, citrate, borate, succinate, maleate or oxalate, or mixtures of the foregoing.

### Claim 12 (depends on 1)

The stent according to claim 1, further comprising a second anti-cancer drug selected from the group consisting of: methotrexate, vinblastine, cisplatin, granulocyte colony-stimulating factor, carboplatin, 5-fluorouracil, ifosfamide, pemetrexed, mitomycin C, capecitabine, Bacillus Calmette-Guerin (BCG) or mixtures of the foregoing.

### Claim 13 (depends on 1)

The stent according to claim 1, further comprising an anti-inflammatory agent, an anti-microbial agent, an antiviral agent, or mixtures of the foregoing.

### Claim 14 (depends on 1)

The stent according to claim 1, wherein the anti-cancer drug is impregnated in the stent by supercritical fluid CO2.

### Claim 15

A ureteral stent comprising a polymeric substrate, wherein the polymeric substrate comprises:
10-50% (w/w) of alginate;
45-85% (w/w) of gelatine;
a polymeric biodegradable resin for coating said polymeric substrate; and
no more than 10% (w/w) of an anti-cancer drug.

### Claim 16

A composition for use in human medicine or veterinary, comprising alginate, gelatine, a polymeric biodegradable resin and no more than 5% (w/w) of an anti-cancer drug,
wherein said composition is administrated in a biodegradable stent,
wherein said stent comprises 10-50% (w/w) of alginate, 45-85% (w/w) of gelatine, a polymeric biodegradable resin for coating said polymeric substrate, and said no more than 5% (w/w) of the anti-cancer drug.

### Claim 17 (depends on 16)

The composition of claim 16, comprising no more than 4.95% (w/w) of the anti-cancer drug.

### Claim 18 (depends on 16)

The composition of claim 16, wherein the anti-cancer drug comprises at least one anti-cancer drug selected from the group consisting of: paclitaxel, epirubicin, doxorubicin, gemcitabine, or mixtures of the foregoing.