(19)
(11)EP 3 122 300 B1

(12)EUROPEAN PATENT SPECIFICATION

(45)Mention of the grant of the patent:
11.03.2020 Bulletin 2020/11

(21)Application number: 14887145.2

(22)Date of filing:  21.08.2014
(51)International Patent Classification (IPC): 
A61F 13/00(2006.01)
A61L 15/42(2006.01)
A61L 15/64(2006.01)
A61L 15/14(2006.01)
A61L 15/44(2006.01)
A61K 9/00(2006.01)
(86)International application number:
PCT/IN2014/000536
(87)International publication number:
WO 2015/145457 (01.10.2015 Gazette  2015/39)

(54)

A READY TO USE BIODEGRADABLE AND BIOCOMPATIBLE DEVICE AND A METHOD OF PREPARATION THEREOF

GEBRAUCHSFERTIGE BIOLOGISCH ABBAUBARE UND BIOKOMPATIBLE VORRICHTUNG SOWIE VERFAHREN ZUR HERSTELLUNG DAVON

DISPOSITIF BIODÉGRADABLE ET BIOCOMPATIBLE PRÊT À L'EMPLOI ET SON PROCÉDÉ DE FABRICATION


(84)Designated Contracting States:
AL AT BE BG CH CY CZ DE DK EE ES FI FR GB GR HR HU IE IS IT LI LT LU LV MC MK MT NL NO PL PT RO RS SE SI SK SM TR

(30)Priority: 24.03.2014 IN 838DE2014

(43)Date of publication of application:
01.02.2017 Bulletin 2017/05

(73)Proprietor: Datt Life Sciences Private Limited
New-Delhi 110065 (IN)

(72)Inventors:
  • DATT, Rajan
    New Delhi 110065 (IN)
  • KUMAR, Ramadhar
    New Delhi 110065 (IN)
  • SHRIVASTAVA, Pallavi
    New Delhi 110065 (IN)

(74)Representative: HGF Limited 
Fountain Precinct Balm Green
Sheffield S1 2JA
Sheffield S1 2JA (GB)


(56)References cited: : 
EP-A1- 2 233 157
WO-A1-2013/048787
CN-A- 101 954 117
US-A1- 2004 106 344
US-A1- 2011 218 472
US-A1- 2013 274 190
EP-A2- 1 952 828
WO-A2-2012/017415
CN-A- 103 394 078
US-A1- 2005 137 512
US-A1- 2011 311 608
  
  • S. LANKALAPALLI AND V. R. M. KOLAPALLI: "Polyelectrolyte Complexes: A Review of their Applicability in Drug Delivery Technology", INDIAN J. PHARM. SCI., vol. 71, no. 5, September 2009 (2009-09), pages 481-487, XP002775323, DOI: 10.4103/0250-474X.58165
  • YUJI YIN ET AL: "A preliminary study on chitosan/gelatin polyelectrolyte complex formation", JOURNAL OF MATERIALS SCIENCE, vol. 40, no. 17, 1 September 2005 (2005-09-01), pages 4649-4652, XP019210652, KLUWER ACADEMIC PUBLISHERS, BO ISSN: 1573-4803, DOI: 10.1007/S10853-005-3929-9
 
Remarks:
The file contains technical information submitted after the application was filed and not included in this specification
 
Note: Within nine months from the publication of the mention of the grant of the European patent, any person may give notice to the European Patent Office of opposition to the European patent granted. Notice of opposition shall be filed in a written reasoned statement. It shall not be deemed to have been filed until the opposition fee has been paid. (Art. 99(1) European Patent Convention).


Description

Field of the invention:



[0001] The present invention relates to the field of Medical Biotechnology.

[0002] More particularly, the invention relates to a wound dressing for stoppage of bleeding.

[0003] The present invention provides a porous gelatin-chitosan matrix usable as a therapeutic carrier, more specifically as a hemostasis product.

[0004] The present invention is a sterile wound dressing product to carry the therapeutic and/or bioactive molecules with preference to accelerate the process of stopping bleeding of the wounds.

[0005] The present invention also relates to a method of preparing such a device for medical field.

Background of the invention:



[0006] Hemostatic products are used to accelerate the process of stopping the bleeding (hemostasis) from surgical or traumatic wounds. Bleeding of the wound may result into loss of blood which in turn may lead to hypovolemic shock leading to tissue and organ damage. In order to stop the bleeding of the wounds several active ingredients like Thrombin, Gelatin, Collagen, Fibrin, Synthetic, etc. are used for manufacturing products which would accelerate the process of stopping the bleeding from wounds. There are several such products known in the art.

[0007] Reference may be made to United States Patent number 8, 133,484, titled "Hemostatic materials and dressing" by Preiss-Bloom, et al. dated 13.03.2012. This invention relates to an adhesive material comprising gelatin and a non-toxic cross-linking material such as transglutaminase. The adhesive material is useful for medical purposes as hemostatic products. The hemostatic products are useful for the treatment of wounded tissue.

[0008] Reference may be made to United States Patent number 8,337,879, titled "Absorbable implants and methods for their use in hemostasis and in the treatment of osseous defects" by Kronenthal dated 25.12.2012. This invention relates to mechanically hemostatic body-absorbable compositions having a putty-like consistency. The compositions preferably comprise a finely powdered, carboxylic acid salt and a liquid block copolymer of ethylene oxide and propylene oxide.

[0009] Reference may be made to United States Patent number 8,252,344, titled "Partially hydrated hemostatic agent" by Hursey dated 28.08.2012. This invention relates to a composition for promoting the formation of clots in blood comprises a zeolite and a binder. The zeolite is adjusted to have a specific moisture content. Processes by which the moisture content is adjusted include drying, re-hydrating, and combinations of drying and re-hydrating. A method of forming the composition comprises the steps of providing a zeolite and adjusting the moisture content such that upon application of the composition to a wound, a heat of hydration is reduced and heat transferred to the wound is reduced. A method of clotting blood flowing from a wound comprises the steps of applying the zeolite to the wound and maintaining the zeolite in contact with the wound for a predetermined amount of time, the zeolite having adjusted moisture content and being capable of producing a controllable exothermic effect on the wound.

[0010] Reference may be made to United States Patent number 8,668,899, titled "Advanced functional biocompatible foam used as a hemostatic agent for compressible and non-compressible acute wounds" by Dowling, et al. dated 11.03.2014. This invention relates to a sprayable polymeric foam hemostat for both compressible and non-compressible (intracavitary) acute wounds. The foam comprises hydrophobically-modified polymers, such as hm-chitosan, or other amphiphilic polymers that anchor themselves within the membrane of cells in the vicinity of the wound. By rapidly expanding upon being released from a canister pressurized with liquefied gas propellant, the foam is able to enter injured body cavities and staunch bleeding. The seal created is strong enough to substantially prevent the loss of blood from these cavities. Hydrophobically-modified polymers inherently prevent microbial infections and are suitable for oxygen transfer required during normal wound metabolism. The amphiphilic polymers form solid gel networks with blood cells to create a physical clotting mechanism that prevent loss of blood.

[0011] US patent application US 2013/0274190 A1 discloses a biomaterial for wound healing and preparation thereof.

[0012] Chinese patent application CN 103394078 A discloses a self-pressurized multi-target collaborative hemostasis degradable hemostatic preparation for injury first aid.

[0013] International patent application WO 2013/048787 A1 discloses novel hemostatic compositions and dressings for bleeding.

[0014] Chinese patent application CN 101954117 A discloses a hemostatic bacteriostatic biological dressing and preparation method thereof.

[0015] European patent application EP 2 233 157 A1 discloses a biocompatible denaturated starch sponge material.

[0016] European patent application EP 1 952 828 A2 discloses a hemostatic textile material.

[0017] US patent application US 2005/0137512 A1 discloses a wound dressing and method for controlling severe, life-threatening bleeding.

[0018] US patent application US 2004/0106344 A1 discloses hemostatic wound dressings containing proteinaceous polymers.

[0019] A review article XP-002775323 is titled polyelectrolyte complexes: a review of their applicability in drug delivery technology.

[0020] A research article XP019210652 is titled a preliminary study on chitosan/gelatin polyelectrolyte complex formation.

[0021] US patent application US 2011/218472 A1 discloses a non-drug based wound dressing polymer film and a method of producing the same.

[0022] US patent application US 2011/311608 A1 discloses a stable chitosan hemostatic implant and methods of manufacture.

[0023] International patent application WO 2012/017415 A2 discloses dry composition wound dressings and adhesives.

[0024] The product of present invention is more effective in solving the purpose as discussed above. The present invention provides a single platform for polyelectrolyte complex (PEC) (to have a combined advantageous features of more than one polymers) to be used as a carrier for multi-therapeuticals (e.g. thrombin, calcium, tranexamic acid to initiate and intensify the immediate clotting and stabilizing) and other bioactive molecules (e.g. D+Glucosamine to further enhance the platelets and blood cells entrapment). Additionally, this provides a biomaterial with growth promoting effects and antimicrobial feature also.

Objects of the invention:



[0025] The main objective of the invention is to provide a device for stopping bleeding immediately and quickly.

[0026] Another main objective of the invention is to provide a ready to use biodegradable and biocompatible device.

[0027] Another objective of the invention is to provide a method of preparation of such device.

[0028] A further objective of the invention is to provide a hemostatic wound dressing meant as therapeutic carrier, more specifically as a Hemostasis product.

[0029] Another objective of the invention is to provide a sterile wound dressing product to carry the therapeutic/bioactive molecules with preference to accelerate the process of stopping bleeding of the wounds.

Summary of the invention:



[0030] Aspects and embodiments of the invention are defined in any one of the accompanying claims.

[0031] The present invention provides a hemostatic wound dressing and a method of preparation thereof. The device of present invention comprises a novel porous matrix composed of Polyelectrolyte complex (PEC) as carrier of plurality of therapeutics to quickly stop bleeding from any type of wounds, i.e. surgical or non-surgical.

[0032] The device of present invention comprises of excellent ventilation features which prevents infections which may be caused due to bleeding.

[0033] Further the embodiments of the present invention may comprise of differential porosity and regulated pores on the same platform in a molecularly integrated PEC matrix.

Brief description of the drawings:



[0034] 

Fig. 1 shows the matrix and its micro structure with vesicular voids. The schematic diagram shows the constituents are held in the matrix of DLS Haemostat.

Fig. 2 shows the Schematic representation-Constituents of DLS Haemostat scaffold and the coagulation cascade.

Fig. 3 shows the SEM photographs of the device showing differential porosity and pore size.

Fig. 4 shows the SEM photograph of the scaffold without drug.

Fig. 5 shows the close magnified SEM photograph of the scaffold without drug.

Fig. 6 shows the SEM photograph of the scaffold with loaded drug.

Fig. 7 shows the close magnified SEM photograph of the scaffold with loaded drug.


Statement of the invention:



[0035] Accordingly the present invention provides a hemostatic wound dressing and a method of manufacturing thereof, said device comprising porous gelatin-chitosan Polyelectrolyte matrix acting as carrier for hemostatic drugs to quickly stop bleeding; said matrix manufactured with interconnected pores of different size; such that said device acts as a drug carrier and transporter to supply and transfer said therapeutics and pharmaceuticals into wounds in order to quickly stop bleeding and to reduce ambient contamination, whenever applied on the wound. The hemostatic drugs comprise tranexamic acid, calcium chloride and, thrombin.

Detailed description of the invention:



[0036] It should be noted that the particular description and embodiments set forth in the specification below are merely exemplary. All the features disclosed in examples of this specification may be replaced by similar other or alternative features performing similar or same or equivalent purpose within the scope of the claims. Thus, unless expressly stated otherwise, they all are within the scope of present invention. Various modifications or substitutions are also possible without departing from the scope of the present invention. Therefore it is to be understood that this specification has been described by way of the most preferred embodiments and for the purposes of illustration and not limitation.

[0037] The present invention provides a ready to use biodegradable and biocompatible device and method of preparation thereof. The device of present invention is a novel porous scaffold to stop bleeding immediately and permanently when applied on the wound. The present invention basically relates to the efficient deployment of a biodegradable, biocompatible medical aid through a novel highly porous scaffold that can be deployed at the point of proposed use. The scaffold under the present invention will allow the medical aid with the ability to quickly stop bleeding and also reduce ambient contamination that could cause secondary infection, preserve tissue after injury and facilitate surgical speed.

[0038] The present invention is a biodegradable and biocompatible dressing, preferably having chitosan and gelatin as base, for control of traumatic bleeding. The ready- to-use patch under the present invention consists of a Gelatin and Chitosan foam, impregnated with clotting agents comprising thrombin, calcium chloride (CaCl2) and Tranexamic Acid. These constituents may be held in the vesicular voids of the matrix, on the internal surface of the sponge which are able to act rapidly when blood flows into the dressing. Once the scaffold under the present invention is in contact with blood, the dressing enables sealing and stabilization of wound surfaces.

[0039] The novel matrix under the present invention provides a device for the natural micro-matrix composed of Polyelectrolyte complex for carrier of more than one type of therapeutics relating to quickly stop bleeding. Further the present scaffold comprises of combined technology of air dry and freeze dry method which provides excellent ventilation property to the scaffold and exudates absorbency to the scaffold of the present invention.

[0040] The present invention aims to overcome the problems in the existing prior arts and provides the novel and unique features in the scaffold by providing on-demand services for differential porosity and regulated pores on the same platform in a molecularly integrated matrix. The technologies involved are the timed patterned physico-chemical treatment of the two or more polymers viz. gelatin and chitosan using a very simplified process to obtain a stable molecular interaction and orientation between the molecules of at least two of the preferred polymers, which results into a highly porous matrix. The used technology provides the proper interaction and orientation between the functional groups of the polymers used, resulted into a typical polyelectrolyte complex (PEC). The most favourable cation, NH3+, rapidly attracts platelets and erythrocytes in blood flow, initiate coagulation mechanism and form strong blood clots at wound site.

[0041] Further under the present invention the novel technology to prepare the scaffold provides two faces to the device. One is more porous with larger pore size and the other is less porous with small pore sizes. The later feature helps to prevent the loss of blood components while the earlier feature allow the blood to enter within the voids of the scaffold resulting into immediate clot generation and migration towards the bleeding site, further interconnected vesicular micro voids hold the drug inside and as a result the encapsulated drugs do not come out of the matrix at significant level.

[0042] Further the highly porous structure of the present invention results into interconnected small voids, provide a large surface area and micro-areas for reactions to occur and thus exert a pseudo-catalytic effect on blood clotting. The whole blood clotting process, the coagulation cascade is activated. The micro- environment aided with hemostatic drugs comprising. thrombin, calcium and tranexamic acid, initiate and intensify the clotting pathway by converting inactive precursor to its active form, so as to form the clot. The co-factor supports the blood clotting process. Anti- fibrinolytic agent in the present invention stabilizes the blood clot and also triggers intrinsic thrombin generation; hence, prolonged compression is not necessary.

[0043] The PEC micro-mesh and body's fibrinogen converted into fibrin forms an efficacious plug and prevents the loss of blood and stops the loss of clotting factor. The novel device of the present invention makes the product light weighted, to be more physical and also altering the blood clotting mechanism. The scaffold of the present invention can be removed easily usually without causing additional/secondary hemorrhage. The present invention could prevent wound infection due to the antibacterial capability of chitosan.

[0044] The novel porous scaffold of the present invention is also capable of being used as a carrier for other therapeutics/ bioactive molecules/ cell (primary or stem cell) towards tissue engineering and other biomaterial applications. Moreover, the scaffold of the present invention is also capable of being used as a cover for the compromised tissues either as acellular or cellular product.

[0045] The utilization of more than one type of polymer & their properties for multi- therapeutics loaded preparation and impregnation of the same with PEC scaffold, a system for more than one types of the pharmaceuticals (like clotting factors, co- factors, clot stabilizers, antibiotics, analgesics, anti-allergic, antioxidants, growth factors, etc.) to get delivered in phase-wise and controlled manner for extended period of time.

[0046] An aspect of the present invention is the sequential timed patterned physico-chemical treatment of the two polymers by using a very simplified process to obtain a stable molecular interaction and orientation between the molecules of the two or more polymers to get highly stabilized porous scaffold without using any cross-linker or any integrated harmful chemicals. Further, the invention comprises of the breakdown of stabilized dried air bubbles and the preparation of said PEC is achieved using a specifically designed aspect ratio of a system for agitation/homogenization. The scaffold matrix of the present invention may comprise of adhesion backing impervious or perforated sheet which would intercalate other matrices in case of large bleeding wound is to be covered.

[0047] The present invention comprises Polyelectrolyte complex porous sponge. The basic structure of the matrix under the present invention is made from preferably absorbent gelatin-chitosan polyelectrolyte complex (GCPEC) which is highly porous and impregnated with substances promoting blood clotting. The blood clotting process occurs within the voids in the presence of co-factor and clotting factors, further the clot is stabilized by anti-fibrinlytic agent. The porous sponge of GCPEC provides a very large surface area for the flowing blood.

[0048] Further the invention comprises of Thrombin which is a plasma protein catalyzing the conversion of fibrinogen into fibrin. This process represents the final phase in the coagulation cascade and leads to the formation of a blood clot. Tranexamic acid is also comprised in the invention which acts as an anti-fibrinlytic agent and stabilizes the blood clot. It also promotes the regeneration of thrombin, and Calcium chloride plays role as clotting factor and supports the coagulation of the blood coming from the wound. This is also a polymerizing and crosslinking factor for the fibrin, also the Tris buffer is used as a carrier solution for the drugs.

[0049] Preparation process of the scaffold under the present invention is outlined below in step by step manner:

1. Preparation of air dried samples



[0050] 


2. Neutralization of air dried samples



[0051] 


3. Drug loading and drying



[0052] 



[0053] So, accordingly the present invention provides a ready to use biodegradable and biocompatible device and a method of manufacturing thereof, said device comprising natural porous scaffold micro-matrix based structure mainly of Polyelectrolyte complex (PEC) acting as carrier of plurality of therapeutics and pharmaceuticals to quickly stop bleeding; said matrix based structure comprising of a plurality of polymers and manufactured as a scaffold comprising differential porosity and regulated pores with interconnected small voids on the same platform in a molecularly integrated matrix; such that said device acts as a drug carrier and transporter to supply and transfer said therapeutics and pharmaceuticals into wounds in order to quickly stop bleeding and to reduce ambient contamination, whenever applied on the wound.

[0054] In another embodiment, said scaffold is produced by the steps:
  1. a) preparing a homogeneous solution of the polymers with different ratio in water and acetic acid and subjecting for air drying to obtain an air dried scaffold;
  2. b) cutting and crushing the above obtained air dried scaffold as per requirement and subjecting for the stabilization either by ammonia vapor or ammonia solution or alkali solution;
  3. c) subsequently washing the product as obtained in step (b) with water and squeezing to remove maximum amount of water;
  4. d) loading the a solution containing tranexamic acid, calcium chloride and thrombin to the washed porous scaffold to obtain the final ready to use product.


[0055] In an embodiment, said method involves physico-chemical treatment of said polymers using a very simplified process in order to obtain a stable molecular interaction and orientation between the molecules of the said polymers, causing an interaction and orientation between the functional groups of the polymers used, resulting into a typical polyelectrolyte complex (PEC), so as to obtain a highly porous matrix.

[0056] In yet another embodiment, said matrix comprises of combined application of air dry and freeze dry method.

[0057] In another embodiment, said matrix comprises differential porosity and regulated pores with interconnected small voids, on the same platform in a molecularly integrated matrix with two faces to the scaffold.

[0058] In another embodiment, said scaffold provides a device for the natural micro-matrix composed of Polyelectrolyte complex for carrier of more than one type of therapeutics in order to quickly stop bleeding.

[0059] In yet another embodiment, said scaffold is produced through physico-chemical treatment of the polymers using simplified process resulting in a stable molecular interaction and orientation between the molecules of the polymers resulting into a highly porous matrix.

[0060] In another embodiment, said scaffold is capable of being used as a carrier for multiple categories of therapeutics and pharmaceuticals and is manufactured as per the requirement.

[0061] In another embodiment, said scaffold is efficiently capable of deployment of a biodegradable, biocompatible medical aid that can be deployed at the point of proposed use as per the requirement.

[0062] In yet another embodiment, said scaffold comprises of two faces wherein one face is more porous with larger pore size and other face is less porous with small pore sizes.

[0063] In another embodiment, said small pores help to prevent the loss of blood components while the large pores allow the blood to enter within the voids of the scaffold resulting into immediate clot generation and migration towards the bleeding site.

[0064] In another embodiment, said scaffold comprises of Polyelectrolyte complex i.e. PEC micro mesh where body's fibrinogen converted into fibrin forms an efficacious plug and prevents the loss of blood and stops the loss of clotting factor.

[0065] In yet another embodiment, said scaffold comprises interconnected small voids, providing a large surface area and micro-areas for reactions to occur and thus exert a pseudo-catalytic effect on blood clotting.

[0066] In another embodiment, said scaffold is capable of being used as a cover for the compromised tissues either as acellular or cellular product.

[0067] In another embodiment, said scaffold is capable of delivering pharmaceuticals and therapeutics in phase-wise and systematically controlled manner, for extended period of time, as and when required.

[0068] The ready to use biodegradable and biocompatible device and method of manufacturing thereof results in to novel, unique and lightweight scaffold, which also possesses the feature of being removed easily usually without causing additional/secondary hemorrhage.

[0069] The ready to use biodegradable and biocompatible device is used to stop the bleeding.

[0070] The ready to use biodegradable and biocompatible device is used as carrier for multiple and plurality of therapeutics and cells and also used for tissue repair/ regeneration/engineering.

Examples:


The following examples are for the purposes of illustration only and therefore should not be construed to limit the scope of the present invention:


Example 1:



[0071] Preparation of the air dried samples: First 100ml of ultrapure water is taken in a beaker. Then 3 gm of gelatin is added in to the beaker containing water and dissolved by heating it. Once the solution is dissolved and heated, it is further Homogenized using stirrer. Then after this 1 ml of Acetic Acid is added and homogenized for 1 min and further 1.5 gm of chitosan is added to the solution and homogenized for 90 min. Once the mixture is homogenized, it is casted in trays and allowed to air dry. Once the sample is dried, it is cut in to the size e.g. 7cm * 7cm.

Neutralization of the air dried samples:



[0072] The crushed samples are soaked in ammonia solution followed by washing and pat and/or vacuum dry.

Drug loading and drying:



[0073] 50mM Tris Buffer is prepared and then 490mg of Tranexamic acid and 98 mg of CaCl2 in Tris buffer are dissolved, further 588 IU of thrombin is added, the final volume is 20 ml. Then the drug solution is loaded to the matrix and lyophilized to obtain drug loaded porous device of the present invention.

Efficacy and biocompatibilitv of the prepared products were evaluated using in-vitro and in-vivo models.


Example 2:


In-vitro testing of blood clotting efficacy


❖ Procedure adopted was direct visual Method:



[0074] Clot formation was assessed in tray (∼20 cm2 SA) with 4 ml blood thinned by 50% using equal volume of PBS and a 1cm2 of the product was added to this. A stop watch is started when the test subjects are affected. The clotting time was measured by tilting the tray by more than 45 degree every 30 sec until firm clotting was detected. The time indicated on the watch is the clotting time. These tests were performed in triplicate.

Example 3:


In vivo efficacy testing for the product



[0075] The effect of the prepared Hemostat on bleeding was tested in Capra aegarus hircus (Domestic Goat). The versions tested are the same in terms of composition and manufacturing quality as the dressings are being used on patients in clinical trials.

[0076] Goat was refrained from food the night before the experiment but had free access to water. Animal was anaesthetized by spinal Lignocaine 2%. Noninvasive blood pressure and pulse was monitored by oscillometric method pre and post-surgery. A scalpel was used to create an experimental wound and a wide opening in the femoral artery.

[0077] The skin of the inguinal area of the thigh was incised longitudinally to the groin to expose the femoral artery vasculator. Lidocain 1-2% was spread on the artery to maximize the dilatation of the vessel. After a brief period of stabilization and recording of baseline data, a uniform incision was made on the femoral artery to induce uncontrolled bleeding. Free bleeding of the puncture site was allowed for 30 seconds followed by application of the cotton gauze (control dressing) or prepared Hemostat for 5 minutes.

[0078] The huge uncontrolled bleeding that resulted was stopped completely in a few minutes by pressing a prepared Hemostat onto the bleeding wound. No secondary bleeding occurred, even when the dressing was carefully separated from the wound. However, it was not possible to stop the bleeding with a control dressing (cotton gauze). Furthermore, the physiological parameters of the tested animal were stabilized.

Advantages of the invention:



[0079] 
  • The present invention stops bleeding within few minutes.
  • Prevents secondary bleeding.
  • The scaffold of the present invention does not stick to the wound.
  • The present invention does not disturb the normal of blood flow.
  • The present invention comprises of improved wound hygiene.
  • The scaffold of the present invention is useful in cases of multiple injury
  • The present invention requires less time to stop bleeding and patient can be addressed immediately.
  • By use of the present scaffold the patient can be transported easily.
  • The present invention helps in earlier mobilization of the patient.
  • Ready-to-use bandage for stopping bleeding of wounds and prevents from loss of life due bleeding.
  • Can be used in surgical procedures including vascular surgical procedures, accidental and combat field.
  • Can be manufactured in any size and shape as per the requirement.
  • Easy to handle.
  • Interconnected Porous in structure.
  • Packed in laminated foil pack to protect it from environmental factors (sunlight & moisture).
  • Thermostat pack (such as Styrofoam) as an insulator and to protect product from getting compressed during transportation or storage.
  • Multiple bandages can be applied for larger wounds.
  • Capable of use for at least 24 hours, however, hemostasis achieves within few minutes only.
  • Can be removed easily without using saline solution or water.
  • Long Shelf life at ambient temperature. Can be disposed-off by burning or degradation.
  • Environment friendly as it is degradable easily.



Claims

1. A hemostatic wound dressing comprising:
a porous gelatin-chitosan polyelectrolyte matrix for use as a hemostatic drug carrier for the stopping of bleeding; the said porous gelatin-chitosan polyelectrolyte matrix comprising interconnected pores of different size to supply and transfer of hemostatic drugs when applied to a wound; wherein the hemostatic drugs comprise tranexamic acid, calcium chloride and thrombin.
 
2. The hemostatic wound dressing as claimed in claim 1, wherein said porous gelatin-chitosan polyelectrolyte matrix provides a carrier for more than one type of hemostatic drug.
 
3. The hemostatic wound dressing as claimed in claim 1, wherein said wound dressing is biodegradable and biocompatible; optionally
wherein said porous gelatin-chitosan polyelectrolyte matrix is used as a cover for a wound, either as an acellular or cellular product.
 
4. The hemostatic wound dressing as claimed in claim 1, wherein said porous gelatin-chitosan polyelectrolyte matrix comprises a first and a second face, wherein the first face is more porous with a larger pore size than the second face which has a smaller pore size than the first face.
 
5. The hemostatic wound dressing as claimed in claim 4, wherein said smaller pores help to prevent the loss of blood components while the larger pores allow the blood to enter within the voids of the matrix resulting in immediate clot generation and migration towards the bleeding site.
 
6. The hemostatic wound dressing as claimed in claim 1, wherein said porous matrix comprises polyelectrolyte complex in the form of a micro-mesh.
 
7. The hemostatic wound dressing as claimed in claim 1, wherein said porous matrix comprises interconnected small voids, providing a large surface area and micro-areas for reactions to occur.
 
8. The hemostatic wound dressing as claimed in claim 1, wherein said porous matrix is usable to of deliver hemostatic drugs in phase-wise and systematically controlled manner, for extended period of time, as and when required.
 
9. The hemostatic wound dressing as claimed in any of the preceding claims, which can be removed from a wound without causing additional/secondary hemorrhage.
 
10. The hemostatic wound dressing as claimed in any of the preceding claims, wherein the hemostatic drugs further comprise glucosamine.
 
11. A method of manufacturing a hemostatic wound dressing of claim 1, wherein said wound dressing is produced by the steps:

a. preparing a homogeneous solution of gelatin and chitosan with different ratio in water and acetic acid and subjecting to air drying to obtain an air dried matrix;

b. cutting and crushing the air dried matrix and subjecting to stabilization either by ammonia vapor or ammonia solution or alkali solution;

c. subsequently washing the product as obtained in step (b) with water;

d. loading a solution containing the tranexamic acid, calcium chloride and thrombin to the washed porous matrix to obtain the final product.


 
12. The method of manufacturing a hemostatic wound dressing as claimed in claim 11, wherein said method involves physico-chemical treatment of gelatin and chitosan to obtain a stable molecular interaction and orientation between the molecules of the said polymers, causing an interaction and orientation between the functional groups of the polymers used, resulting in a polyelectrolyte complex, so as to obtain a highly porous matrix.
 
13. The method of manufacturing a hemostatic wound dressing as claimed in claim 11, wherein the said air dried matrix is obtained by the combined application of air drying and freeze drying.
 


Ansprüche

1. Hämostatischer Wundverband, der umfasst:
eine poröse Gelatine-Chitosan-Polyelektrolytmatrix zur Verwendung als ein hämostatischer Wirkstoffträger zum Stoppen einer Blutung; wobei die poröse Gelatine-Chitosan-Polyelektrolytmatrix miteinander verbundene Poren unterschiedlicher Größe umfasst, um hämostatische Arzneimittel zuzuführen und zu übertragen, wenn sie auf eine Wunde aufgebracht werden; wobei die hämostatischen Arzneimittel Tranexamsäure, Calciumchlorid und Thrombin umfassen.
 
2. Hämostatischer Wundverband nach Anspruch 1, wobei die poröse Gelatine-Chitosan-Polyelektrolytmatrix einen Träger für mehr als eine Art eines hämostatischen Arzneimittels bereitstellt.
 
3. Hämostatischer Wundverband nach Anspruch 1, wobei der Wundverband biologisch abbaubar und biokompatibel ist;
wobei optional die poröse Gelatine-Chitosan-Polyelektrolytmatrix als eine Wundabdeckung verwendet wird, entweder als ein azelluläres oder ein zelluläres Produkt.
 
4. Hämostatischer Wundverband nach Anspruch 1, wobei die poröse Gelatine-Chitosan-Polyelektrolytmatrix eine erste und eine zweite Fläche umfasst, wobei die erste Fläche poröser mit einer größeren Porengröße als die zweite Fläche ist, die eine kleinere Porengröße als die erste Fläche aufweist.
 
5. Hämostatischer Wundverband nach Anspruch 4, wobei die kleineren Poren dazu beitragen, den Verlust von Blutbestandteilen zu verhindern, während die größeren Poren es dem Blut erlauben, in die Hohlräume der Matrix einzutreten, was zu einer sofortigen Gerinnselbildung und Migration zu der Blutungsstelle führt.
 
6. Hämostatischer Wundverband nach Anspruch 1, wobei die poröse Matrix einen Polyelektrolytkomplex in der Form eines feinmaschigen Gitters umfasst.
 
7. Hämostatischer Wundverband nach Anspruch 1, wobei die poröse Matrix miteinander verbundene kleine Hohlräume umfasst, die einen großen Oberflächenbereich und Mikrobereiche für das Auftreten von Reaktionen bereitstellen.
 
8. Hämostatischer Wundverband nach Anspruch 1, wobei die poröse Matrix für eine Abgabe von hämostatischen Arzneimitteln in phasenweiser und systematisch gesteuerter Weise über einen längeren Zeitraum nach Bedarf verwendet werden kann.
 
9. Hämostatischer Wundverband nach einem der vorhergehenden Ansprüche, der von einer Wunde entfernt werden kann, ohne eine zusätzliche/sekundäre Blutung zu verursachen.
 
10. Hämostatischer Wundverband nach einem der vorhergehenden Ansprüche, wobei die hämostatischen Arzneimittel ferner Glucosamin umfassen.
 
11. Verfahren zum Herstellen eines hämostatischen Wundverbandes nach Anspruch 1, wobei der Wundverband durch die Schritte produziert wird:

a. Herstellen einer homogenen Lösung aus Gelatine und Chitosan mit einem unterschiedlichen Verhältnis von Wasser und Essigsäure und Unterziehen einer Lufttrocknung, um eine luftgetrocknete Matrix zu erhalten;

b. Schneiden und Zerkleinern der luftgetrockneten Matrix und Stabilisieren entweder durch Ammoniakdampf oder Ammoniaklösung oder Alkalilösung;

c. anschließendes Waschen des in Schritt (b) erhaltenen Produkts mit Wasser;

d. Beladen der gewaschenen porösen Matrix mit einer Lösung, die Tranexamsäure, Calciumchlorid und Thrombin enthält, um das Endprodukt zu erhalten.


 
12. Verfahren zum Herstellen eines hämostatischen Wundverbandes nach Anspruch 11, wobei das Verfahren eine physikalisch-chemische Behandlung von Gelatine und Chitosan einschließt, um eine stabile molekulare Wechselwirkung und Orientierung zwischen den Molekülen der Polymere zu erhalten, was eine Wechselwirkung und Orientierung zwischen den funktionellen Gruppen der verwendeten Polymere verursacht, was zu einem Polyelektrolytkomplex führt, um eine hochporöse Matrix zu erhalten.
 
13. Verfahren zum Herstellen eines hämostatischen Wundverbandes nach Anspruch 11, wobei die luftgetrocknete Matrix durch kombinierte Anwendung eines Lufttrocknens und eines Gefriertrocknens erhalten wird.
 


Revendications

1. Pansement hémostatique comprenant :
une matrice poreuse de polyélectrolyte de gélatine-chitosane devant être utilisée comme véhicule de médicaments hémostatiques pour arrêter un saignement ; ladite matrice poreuse de polyélectrolyte de gélatine-chitosane comprenant des pores interconnectés de taille différente pour fournir et transférer des médicaments hémostatiques lorsqu'elle est appliquée à une plaie ; dans lequel les médicaments hémostatiques comprennent l'acide tranexamique, le chlorure de calcium et la thrombine.
 
2. Pansement hémostatique selon la revendication 1, dans lequel ladite matrice poreuse de polyélectrolyte de gélatine-chitosane fournit un véhicule pour plus d'un type de médicament hémostatique.
 
3. Pansement hémostatique selon la revendication 1, ledit pansement étant biodégradable et biocompatible ; optionnellement dans lequel ladite matrice poreuse de polyélectrolyte de gélatine-chitosane est utilisée pour couvrir une plaie, comme produit soit acellulaire, soit cellulaire.
 
4. Pansement hémostatique selon la revendication 1, dans lequel ladite matrice poreuse de polyélectrolyte de gélatine-chitosane comprend une première face et une deuxième face, la première face étant plus poreuse avec une taille de pores plus grande que la deuxième face qui a une taille de pores plus petite que la première face.
 
5. Pansement hémostatique selon la revendication 4, dans lequel lesdits pores plus petits contribuent à prévenir la perte de composants sanguins, tandis que les pores plus grands permettent au sang de pénétrer dans les vides de la matrice pour entraîner une génération immédiate de caillots et leur migration vers le site de l'hémorragie.
 
6. Pansement hémostatique selon la revendication 1, dans lequel ladite matrice poreuse comprend un complexe polyélectrolyte sous la forme d'un microtamis.
 
7. Pansement hémostatique selon la revendication 1, dans lequel ladite matrice poreuse comprend de petits vides interconnectés offrant une grande superficie et des micro-surfaces permettant aux réactions de se produire.
 
8. Pansement hémostatique selon la revendication 1, dans lequel ladite matrice poreuse est utilisable pour administrer les médicaments hémostatiques par phases et de manière contrôlée systématiquement, pendant des durées prolongées, selon besoin et au moment voulu.
 
9. Pansement hémostatique selon l'une quelconque des revendications précédentes, qui peut être enlevé d'une plaie sans causer d'hémorragie supplémentaire/secondaire.
 
10. Pansement hémostatique selon l'une quelconque des revendications précédentes, dans lequel les médicaments hémostatiques comprennent en outre la glucosamine.
 
11. Procédé de fabrication d'un pansement hémostatique selon la revendication 1, dans lequel le pansement est produit par les étapes de :

a. préparation d'une solution homogène de gélatine et de chitosane ayant un rapport différent dans l'eau et l'acide acétique et application de séchage à l'air pour obtenir une matrice séchée à l'air ;

b. découpage et broyage de la matrice séchée à l'air et application d'une stabilisation soit par vapeur d'ammoniac soit par solution d'ammoniac ou solution d'alcali ;

c. lavage consécutif à l'eau du produit obtenu à l'étape (b) ;

d. chargement d'une solution contenant l'acide tranexamique, le chlorure de calcium et la thrombine dans la matrice poreuse lavée pour obtenir le produit final.


 
12. Procédé de fabrication d'un pansement hémostatique selon la revendication 11, ledit procédé comportant le traitement physico-chimique de gélatine et de chitosane pour obtenir une interaction et une orientation moléculaires stables entre les molécules desdits polymères, causant une interaction et une orientation entre les groupes fonctionnels des polymères utilisés, procurant un complexe polyélectrolyte, de manière à obtenir une matrice hautement poreuse.
 
13. Procédé de fabrication d'un pansement hémostatique selon la revendication 11, dans lequel ladite matrice séchée à l'air est obtenue par l'application combinée de séchage à l'air et de lyophilisation.
 




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Cited references

REFERENCES CITED IN THE DESCRIPTION



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Patent documents cited in the description