WO2015026225A1 - Bilayer hydrocolloid films containing therapeutic agents - Google Patents

Bilayer hydrocolloid films containing therapeutic agents Download PDF

Info

Publication number
WO2015026225A1
WO2015026225A1 PCT/MY2014/000222 MY2014000222W WO2015026225A1 WO 2015026225 A1 WO2015026225 A1 WO 2015026225A1 MY 2014000222 W MY2014000222 W MY 2014000222W WO 2015026225 A1 WO2015026225 A1 WO 2015026225A1
Authority
WO
WIPO (PCT)
Prior art keywords
water
hydrocolloid
bilayer
solvent system
hydrogel
Prior art date
Application number
PCT/MY2014/000222
Other languages
French (fr)
Inventor
Shiow Fern NG
Hnin Ei THU
Original Assignee
Universiti Kebangsaan Malaysia
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 Universiti Kebangsaan Malaysia filed Critical Universiti Kebangsaan Malaysia
Publication of WO2015026225A1 publication Critical patent/WO2015026225A1/en

Links

Classifications

    • 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
    • A61K9/0053—Mouth and digestive tract, i.e. intraoral and peroral administration
    • A61K9/006—Oral mucosa, e.g. mucoadhesive forms, sublingual droplets; Buccal patches or films; Buccal sprays
    • 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
    • A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
    • A61K31/19—Carboxylic acids, e.g. valproic acid
    • A61K31/192—Carboxylic acids, e.g. valproic acid having aromatic groups, e.g. sulindac, 2-aryl-propionic acids, ethacrynic acid 
    • 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
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
    • A61K47/10—Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
    • A61K47/36—Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • 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

Definitions

  • Wound healing is defined as body's replacement injured tissues with living tissues.
  • wound care It is a dynamic and intricate process which involve multiple cellular and matrix components act together to restore the integrity of injured tissue.
  • the primary goals of wound care are rapid wound closure and leave minimal or aesthetically acceptable scar.
  • Wound management is important in providing optimum healing milieu for wound healing.
  • the desirable wound dressing may therefore serve among the purposes of (a) to provide moisture and occlusion, (b) protection from infections and contamination, (c) debridement, and (d) easy application and removal avoiding dressing-related trauma.
  • drug-loaded wound dressings are used to treat wound locally such as anti-infections due to secondary infection or for pain control, especially in chronic wounds.
  • Various wound care products are available in the wound care management market and they are targeted towards the treatment of both acute and chronic wounds.
  • hydrocolloid dressings cast from hydrogels, sometimes know as hydrocolloid dressings, have been developed and uses as the first major advances in moist wound management. Wound healing is promoted by dressings that maintain a moist environment. Hydrocolloid has the ability to form gels upon contact with wound exudates and the high absorption occurs via strong hydrophilic gel formation. The formation of gel allows excess fluid to escape without permitting wound desiccation.
  • the fluid handling capacity of hydrocolloid dressings depends on many factors such as the physicochemical properties and the design of the dressing.
  • the object of the present invention is a bilayer pharmaceutical hydrocolloid film, suitable for use as slow-release dressing for wound or mucosa surfaces.
  • the pharmaceutical hydrocolloid film contains two layers, hence bilayer.
  • the lower layer comprises a solvent system comprising about 6 % v/v glycerol as a plasticizer, and about 94 % v/v of mixture of solvents containing water and optionally further water-miscible pharmaceutically acceptable solvents, such as alcohols or glycols.
  • the lower layer contains a hydrogel-forming polymer in the amount of
  • Suitable hydrogel-forming polymers include sodium alginate, gelatine, polymethacrylate, poly(methylmethacrylate), or mixtures of polymers.
  • the upper layer comprises a solvent system and a hydrogel-forming polymer in the same amounts as the lower layer, and further a therapeutic agent in the amount of up to 10 % w/w, relative to the weight of the solvent system.
  • the solvent system is selected according to the type of the therapeutic agent, so that the therapeutic agent is soluble in the selected solvent system.
  • Mucosa surfaces can include buccal, vaginal, rectal or nasal mucosa, and other mucosa tissue surfaces.
  • the therapeutic agent is a poorly water soluble drug.
  • the mixture of solvents selected for the preferred embodiment is thus water, propylene glycol and ethanol.
  • Another object of the present invention is a method of preparation of the bilayer pharmaceutical hydrocolloid films, which comprises first preparing the lower drug-free layer by vortexing sodium alginate and optionally also gelatin in water at the temperature of 35 to 100 °C, then cooling it at continuous stirring and subsequently adding glycerol, still at stirring, and then pouring the resulting gel into a casting container, and drying it at 35-40 °C leaving it to solidify, and then vortexing sodium alginate containing therapeutic agent and optionally also gelatin in water at the temperature of 35 to 100 °C, then cooling it at continuous stirring and subsequently adding glycerol, still at stirring, and then pouring the resulting gel onto the upper layer and drying it at 35-40 °C.
  • Yet another object of the present invention is the use of the bilayer hydrocolloid pharmaceutical film for covering injured mucosa surfaces.
  • Therapeutic agent is a drug or active ingredient which have therapeutic effect on human body.
  • bovine skin Type B (Sigma, USA), propylene glycol (R & M chemicals, U. ), 99 % v/v ethanol (Merck, Germany) and glycerol (Merck, Germany) were used for the preparation of solvent evaporated dried films.
  • SApowder wasweighed.SA powder wasdissolved in distilled waterwhich was gradually heated to 40 °C on a hot plate stirreruntil a uniform solution was obtained.At 40 °C, the beaker was removed from heat and the solution was cooled and continuously stirred until a uniform gel was obtained. Then, 6 mL of glycerol as a plasticizer was added into the SA gel while stirred continuously. The gel was then covered with para-film and left to stand for approximately 10 minutes to remove the air bubbles which were entrapped in the SA gel. The gels were casted as lower layers by pouring 12.5 ⁇ 0.04 g of gel on petri dishes. The layers were dried in an incubator at 37 °C and 50 % RH for 72 hours.
  • gelatin/alginate films initially 4.01 ⁇ 0.02 g of gelatin powder was weighed and dissolved in 94 mL of warm distilled water (90#C) until a clear and uniform gelatin solution was formed. Afterwards, 6.03 ⁇ 0.03 g of SA powder was added into the gelatin solution and the procedure was continued in the same way as for sodium alginate films.
  • the SA or SA/gelatin gel was prepared with the same procedure as the drug- free upper layer. Ibuprofen solution was added into the SA or SA/gelatin gel. The gels were casted as lower layers by pouring 12.5 ⁇ 0.04 g of gel on the lower layers which were previously dried and dried in an incubator at 37 °C and 50 % RH for 72 hours. After 72 hours, the dried films were weighed, covered with the lids of the plastic petri dishes and kept in the dessicator containing silica gel beads at room temperature (25 ⁇ 2 °C) for further studies.

Abstract

The present invention provides a bilayer hydrocolloid pharmaceutical film, suitable for use as slow-release dressing, containing a lower layer comprising glycerol, water-based solvents and a hydrogel-forming polymer, and a upper layer comprising glycerol, water-based solvents, a hydrogel-forming polymer and a therapeutic agent. The invention further includes a method of preparation of the pharmaceutical film and its use as mucosa surface dressing.

Description

Description
BILAYER HYDROCOLLOID FILMS CONTAINING THERAPEUTIC AGENTS
[1 ] Background Art
[2] Wound healing is defined as body's replacement injured tissues with living tissues.
It is a dynamic and intricate process which involve multiple cellular and matrix components act together to restore the integrity of injured tissue. The primary goals of wound care are rapid wound closure and leave minimal or aesthetically acceptable scar. Wound management is important in providing optimum healing milieu for wound healing. Depending on the severity of the wound, the desirable wound dressing may therefore serve among the purposes of (a) to provide moisture and occlusion, (b) protection from infections and contamination, (c) debridement, and (d) easy application and removal avoiding dressing-related trauma. Occasionally, drug-loaded wound dressings are used to treat wound locally such as anti-infections due to secondary infection or for pain control, especially in chronic wounds. Various wound care products are available in the wound care management market and they are targeted towards the treatment of both acute and chronic wounds. Among the modern wound dressings, dressings cast from hydrogels, sometimes know as hydrocolloid dressings, have been developed and uses as the first major advances in moist wound management. Wound healing is promoted by dressings that maintain a moist environment. Hydrocolloid has the ability to form gels upon contact with wound exudates and the high absorption occurs via strong hydrophilic gel formation. The formation of gel allows excess fluid to escape without permitting wound desiccation. However, the fluid handling capacity of hydrocolloid dressings depends on many factors such as the physicochemical properties and the design of the dressing.
[3] Previously, research has shown that composite films have improved physical, transport and mechanical properties compared to those of single component-based films. The term 'bilayer film' is used to describe two hydrocolloid layers, one cast over another. Recently, bilayer composite film systems based on various biopolymers are extensively investigated in food technology and bioengineering applications as edible films due to their better mechanical properties, higher moisture retaining properties and ease of preparation relatively to other film formulation. However, little is known on bilayers in mucosa healing and drug delivery applications.
[4] Disclosure of the invention
[5] The object of the present invention is a bilayer pharmaceutical hydrocolloid film, suitable for use as slow-release dressing for wound or mucosa surfaces.
[6] The pharmaceutical hydrocolloid film contains two layers, hence bilayer.
[7] The lower layer comprises a solvent system comprising about 6 % v/v glycerol as a plasticizer, and about 94 % v/v of mixture of solvents containing water and optionally further water-miscible pharmaceutically acceptable solvents, such as alcohols or glycols.
[8] It was discovered that a low glycerol content (lower than 6 % v/v) produces hard and brittle films which are difficult to remove from the casting containers. High glycerol content (more than 6 % v/v) produces very elastic films that are difficult to handle and slows down drying of the films.
[9] Furthermore, the lower layer contains a hydrogel-forming polymer in the amount of
2-12 % w/w, the amount being relative to the weight of the solvent system. Suitable hydrogel-forming polymers include sodium alginate, gelatine, polymethacrylate, poly(methylmethacrylate), or mixtures of polymers.
[10] The upper layer comprises a solvent system and a hydrogel-forming polymer in the same amounts as the lower layer, and further a therapeutic agent in the amount of up to 10 % w/w, relative to the weight of the solvent system.
[1 1] The solvent system is selected according to the type of the therapeutic agent, so that the therapeutic agent is soluble in the selected solvent system.
[12] Mucosa surfaces can include buccal, vaginal, rectal or nasal mucosa, and other mucosa tissue surfaces.
[13] In a preferred embodiment, the therapeutic agent is a poorly water soluble drug.
The mixture of solvents selected for the preferred embodiment is thus water, propylene glycol and ethanol. Preferably, 10-30% v/v of propylene glycol 5% v/v of ethanol and water 59-79% v/v is used as the mixture of solvents in the solvent system.
[14] Another object of the present invention is a method of preparation of the bilayer pharmaceutical hydrocolloid films, which comprises first preparing the lower drug-free layer by vortexing sodium alginate and optionally also gelatin in water at the temperature of 35 to 100 °C, then cooling it at continuous stirring and subsequently adding glycerol, still at stirring, and then pouring the resulting gel into a casting container, and drying it at 35-40 °C leaving it to solidify, and then vortexing sodium alginate containing therapeutic agent and optionally also gelatin in water at the temperature of 35 to 100 °C, then cooling it at continuous stirring and subsequently adding glycerol, still at stirring, and then pouring the resulting gel onto the upper layer and drying it at 35-40 °C.
[15] Yet another object of the present invention is the use of the bilayer hydrocolloid pharmaceutical film for covering injured mucosa surfaces.
[16] Therapeutic agent is a drug or active ingredient which have therapeutic effect on human body.
[17] Examples of carrying out the Invention
[18] Materials and methods :
[19] Sodium alginate (SA) (Sigma, USA), ibuprofen (Sigma, USA), gelatin (from
bovine skin, Type B) (Sigma, USA), propylene glycol (R & M chemicals, U. ), 99 % v/v ethanol (Merck, Germany) and glycerol (Merck, Germany) were used for the preparation of solvent evaporated dried films.
[20] Example 1 : Preparation of bilayer pharmaceutical hydrocolloid films
[21 ] For sodium alginate films, initially 6.03±0.02 gofsodium alginate
(SA)powderwasweighed.SA powder wasdissolved in distilled waterwhich was gradually heated to 40 °C on a hot plate stirreruntil a uniform solution was obtained.At 40 °C, the beaker was removed from heat and the solution was cooled and continuously stirred until a uniform gel was obtained. Then, 6 mL of glycerol as a plasticizer was added into the SA gel while stirred continuously. The gel was then covered with para-film and left to stand for approximately 10 minutes to remove the air bubbles which were entrapped in the SA gel. The gels were casted as lower layers by pouring 12.5±0.04 g of gel on petri dishes. The layers were dried in an incubator at 37 °C and 50 % RH for 72 hours.
[22] For gelatin/alginate films, initially 4.01 ±0.02 g of gelatin powder was weighed and dissolved in 94 mL of warm distilled water (90#C) until a clear and uniform gelatin solution was formed. Afterwards, 6.03±0.03 g of SA powder was added into the gelatin solution and the procedure was continued in the same way as for sodium alginate films.
[23] The drug-loaded layers,firstly,5.03±0.03 g of ibuprofen (as an example of a
therapeutic agent)was dissolved inpropylene glycol (PG) and ethanol, as shown in Table 1. The SA or SA/gelatin gel was prepared with the same procedure as the drug- free upper layer. Ibuprofen solution was added into the SA or SA/gelatin gel. The gels were casted as lower layers by pouring 12.5±0.04 g of gel on the lower layers which were previously dried and dried in an incubator at 37 °C and 50 % RH for 72 hours. After 72 hours, the dried films were weighed, covered with the lids of the plastic petri dishes and kept in the dessicator containing silica gel beads at room temperature (25±2 °C) for further studies.
[24] Table 1 Formulations of the bilayer films B 1 -B6.
Figure imgf000004_0001
Figure imgf000005_0001

Claims

Claims
[1 ] A bilayer hydrocolloid pharmaceutical film, suitable for use as slow-release mucosa surface dressing, containing
- a lower layer comprising:
- a solvent system comprising about 6 % v/v glycerol as a plasticizer, and about 94 % v/v of mixture of solvents containing water and optionally further water- miscible pharmaceutically acceptable solvents;
- a hydrogel-forming polymer in the amount of 2- 12 % w/w, the amount being relative to the weight of the solvent system;
- an upper layer comprising:
- a solvent system comprising about 6 % v/v glycerol as a plasticizer, and about 94 % v/v of mixture of solvents containing water and optionally further water- miscible pharmaceutically acceptable solvents;
- a hydrogel-forming polymer in the amount of 2-12 % w/w, the amount being relative to the weight of the solvent system;
- a therapeutic agent in the amount of up to 10 % w/w, relative to the weight of the solvent system.
[2] The pharmaceutical hydrocolloid film according to claim 1 , wherein the
therapeutic agent is a poorly water-soluble drug, such as ibuprofen, andthe mixture of solvents is water, propylene glycol and ethanol.
[3] A method of preparation of the bilayer hydrocolloid pharmaceutical film of any of claims 1 to 2, which comprises
preparing a lower layer by vortexing the hydrogel-forming polymer in water at the temperature of 35 to 100 °C, then cooling it at continuous stirring and subsequently adding glycerol, still at stirring, and then pouring the resulting gel into a casting container and drying it at 35-40 °C; and
preparing an upper layer by vortexing the hydrogel-forming polymer in water at the temperature of 35 to 100 °C, then cooling it at continuous stirring and subsequently adding glycerol and solution of the therapeutic agent, still at stirring, and then pouring the resulting gel onto the lower layer and drying it at 35-40 °C.
[4] Use of the bilayer hydrocolloid pharmaceutical film of any of claims 1 to 2 for covering injured mucosa surfaces.
PCT/MY2014/000222 2013-08-22 2014-08-20 Bilayer hydrocolloid films containing therapeutic agents WO2015026225A1 (en)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
MYPI2013701483 2013-08-22
MYPI2013701483A MY184693A (en) 2013-08-22 2013-08-22 Bilayer hydrocolloid films containing therapeutic agents

Publications (1)

Publication Number Publication Date
WO2015026225A1 true WO2015026225A1 (en) 2015-02-26

Family

ID=52483934

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/MY2014/000222 WO2015026225A1 (en) 2013-08-22 2014-08-20 Bilayer hydrocolloid films containing therapeutic agents

Country Status (2)

Country Link
MY (1) MY184693A (en)
WO (1) WO2015026225A1 (en)

Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN106267357A (en) * 2016-08-09 2017-01-04 上海交通大学 A kind of repair the two-layer compound hydrogel of osteochondral tissue, preparation method and application
US9968800B2 (en) 2016-02-09 2018-05-15 Luma Therapeutics, Inc. Methods, compositions and apparatuses for treating psoriasis by phototherapy
US10058711B2 (en) 2014-02-26 2018-08-28 Luma Therapeutics, Inc. Phototherapy dressing for treating psoriasis
WO2024012190A1 (en) * 2022-07-11 2024-01-18 西南交通大学 Double-layer bionic drug-loaded hydrogel, and preparation and use thereof

Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5741510A (en) * 1994-03-30 1998-04-21 Lectec Corporation Adhesive patch for applying analgesic medication to the skin
US6399091B1 (en) * 1999-06-04 2002-06-04 Lts Lohamann Therapie-Systeme Ag Wound dressing for the controlled release of active substance to wounds, and process for its manufacture
US20050137272A1 (en) * 2003-09-08 2005-06-23 Olav Gaserod Gelled biopolymer based foam
CN202682163U (en) * 2012-06-08 2013-01-23 稳健实业(深圳)有限公司 Double-layer hydrocolloid medical dressing
WO2013029796A1 (en) * 2011-09-02 2013-03-07 BLüCHER GMBH Multi-layered wound dressing containing an hydrocolloid and activated carbon

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5741510A (en) * 1994-03-30 1998-04-21 Lectec Corporation Adhesive patch for applying analgesic medication to the skin
US6399091B1 (en) * 1999-06-04 2002-06-04 Lts Lohamann Therapie-Systeme Ag Wound dressing for the controlled release of active substance to wounds, and process for its manufacture
US20050137272A1 (en) * 2003-09-08 2005-06-23 Olav Gaserod Gelled biopolymer based foam
WO2013029796A1 (en) * 2011-09-02 2013-03-07 BLüCHER GMBH Multi-layered wound dressing containing an hydrocolloid and activated carbon
CN202682163U (en) * 2012-06-08 2013-01-23 稳健实业(深圳)有限公司 Double-layer hydrocolloid medical dressing

Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US10058711B2 (en) 2014-02-26 2018-08-28 Luma Therapeutics, Inc. Phototherapy dressing for treating psoriasis
US9968800B2 (en) 2016-02-09 2018-05-15 Luma Therapeutics, Inc. Methods, compositions and apparatuses for treating psoriasis by phototherapy
CN106267357A (en) * 2016-08-09 2017-01-04 上海交通大学 A kind of repair the two-layer compound hydrogel of osteochondral tissue, preparation method and application
WO2024012190A1 (en) * 2022-07-11 2024-01-18 西南交通大学 Double-layer bionic drug-loaded hydrogel, and preparation and use thereof

Also Published As

Publication number Publication date
MY184693A (en) 2021-04-17

Similar Documents

Publication Publication Date Title
US10143755B2 (en) Anhydrous hydrogel composition and delivery system
El-Refaie et al. Novel curcumin-loaded gel-core hyaluosomes with promising burn-wound healing potential: development, in-vitro appraisal and in-vivo studies
Mukherjee et al. Development and characterization of chitosan-based hydrogels as wound dressing materials
JP4937269B2 (en) Sustained release film preparation for wound treatment containing epidermal growth factor
EP1602365A1 (en) Pharmaceutical composition for topical use in form of xerogels or films and methods for production
Yin et al. Rhein incorporated silk fibroin hydrogels with antibacterial and anti-inflammatory efficacy to promote healing of bacteria-infected burn wounds
JPH10512892A (en) Pharmaceutical form for administration of active substance to wound site
WO2015026225A1 (en) Bilayer hydrocolloid films containing therapeutic agents
JP7075403B2 (en) A method for manufacturing a porous hydrogel sheet and a porous hydrogel sheet manufactured by the manufacturing method.
Xiong et al. Immunomodulatory hydrogels: advanced regenerative tools for diabetic foot ulcer
Layek et al. Design, development, and characterization of imiquimod-loaded chitosan films for topical delivery
Farazin et al. Natural biomarocmolecule-based antimicrobial hydrogel for rapid wound healing: A review
Pandey et al. Evaluating the efficacy of different curcumin polymorphs in transdermal drug delivery
WO2019180748A1 (en) Probiotic formulation and uses thereof
CZ302380B6 (en) Dry substance of hydrogel to cover wounds and process for preparing thereof
US10583216B2 (en) Scaffold compositions for tissue repair
Ei Bilayer hydrocolloid films containing therapeutic agents
RU2611401C1 (en) Method for preparation of drug with locally-acting erythropoietin
Tabassum et al. Development of antimicrobial colloidal silver incorporated lyophilized biopolymer wafers for wound care
WO2020036526A1 (en) A biphasic hydrogel formulation and methods of production and use thereof
Gu et al. Research progress related to thermosensitive hydrogel dressings in wound healing: a review
Chevala et al. Multifunctional and multilayer surgical sealant for a better patient safety
Deb et al. Formulation and evaluation of curcumin loaded nanofilms for the treatment of wounds
JPS63160661A (en) Surgical composition
de OliveiraFerreira Internship Reports and Thesis" Halloysite Clay Nanotubes for Life Sciences Applications-From Drug/Protein Encapsulation to Bioscaffold"

Legal Events

Date Code Title Description
121 Ep: the epo has been informed by wipo that ep was designated in this application

Ref document number: 14837442

Country of ref document: EP

Kind code of ref document: A1

NENP Non-entry into the national phase

Ref country code: DE

122 Ep: pct application non-entry in european phase

Ref document number: 14837442

Country of ref document: EP

Kind code of ref document: A1