FIELD OF THE INVENTION
The present invention relates to a formulation of Super Porous Interpolymeric Complex (SPIPC) for short term management of heavy bleeding promptly, caused due to surgery, trauma, accidental conditions, more particularly the formulation is comprising of naturally occurring polysaccharides chitosan, alginate which are ionically crosslinked using calcium based ionic linker. The present invention further relates to the processes for the preparation of said Super Porous Interpolymeric Complex (SPIPC) which has clotting time of 30 to 200 seconds.

BACKGROUND OF THE INVENTION

Every year, around 5.8 million people die worldwide due to events related to trauma, of which about 40% of trauma related deaths are due to hemorrhage or its consequences. Trauma is the fourth leading cause of death in India and accounts for 8.5% of all deaths. It has been reported that uncontrolled hemorrhage causes almost 50% of battlefield deaths and 80% of civilian trauma deaths in India.
Severe hemorrhage can begin with a cascade of life-threatening medical problems including hemorrhage, impaired resuscitation, shock, inflammation coagulopathy and many of these occur simultaneously. The severity of each problem is commonly associated with the extent of overall blood loss. Low blood pressure due to blood loss indicates immediate complications, including the incidence of multiple organ failure and life-threatening infections. The first hour management i.e. golden hour management for these conditions are of prime importance and non-availability of effective treatment during this time leads to death of patients.
Conventional approaches such as manual pressure, cauterization, or sutures may be time consuming and are not always effective in controlling bleeding. Over the years, a number of topical hemostatic agents have been developed to control bleeding resulting from traumatic injury. Some agents such as collagen-based powders, hemostatic factors (e.g. thrombin, fibrinogen) where the fibers are formed from electrospun glass plus a secondary fiber (e.g. silk, ceramic, bamboo, jute, rayon), hemostatic multilayer bandage that comprises a thrombin layer between two fibrinogen layers, fibers produced by an electro-processing technique, cellulose and dextran combinations, sponges, or cloth are of a particulate nature show promising effects but their main limitations are lack of efficacy in severe bleeding. Ideal hemostatic materials must exhibit quick and effective control of bleeding in a wide range of conditions and from a variety of sources within a few seconds, even when applied to an actively bleeding site through a pool of blood; sustainable hemostasis duration for several hours if used on battlefield reflecting delayed evacuation; easy administration even by a
layperson; ease of sterilization; simple to store; prolonged stability, even under extreme conditions; low cost; and good biocompatibility and no adverse effects, no thromboembolic complications. The criteria for material selection should be based on probability of success in vivo, stability, ease of use, and ease of manufacturing.
Conventional hemostatic materials based on fibrin, collagen, gelatin, chitosan and cellulose have still drawn attention and continuously studied in different animal models and clinical settings showing variable efficacy (5 to 10 minutes of hemostatic claim).
However, they generally fail to stop aggressive / heavy bleeding. It is noteworthy that some of these biomaterials, such as chitosan, are the base material in the advanced hemostatic products.
Patent US 20140322341 discloses a novel hemostatic patch comprises chitosan and Neuropeptide Y that may be used to control and/or arrest bleeding in patients. The patch comprises a mucoadhesive and a compound that causes vasoconstriction. Also disclosed are methods of using the novel hemostatic patch. This system used glutaraldehyde as a crosslinking agent which leads to pendant aldehydes which are harmful to biological milieu.
Patent US 20070166387 A1 discloses granules or particles made of a chitosan material either carries within it, or has interspersed with it, a polymer mesh material of poly-4-hydroxy butyrate. The granule or particle can be carried within this polymer mesh socklet and are used to treat intracavity bleeding. The material can be easily removed without disturbing the wound surface. However, the chitosan based SPIPC described in our formulation can also be easily removed by using normal saline.
Patent US 20070104769 A1 discloses bio-absorbable, water-soluble hemostatic cellulose based gauze matrix structures, including one or more species of chitosan, etherized cellulose, nonionic surfactant, water-soluble polysaccharide hydrocolloid and/or gum. Approximately 85% to 95% deacetylated decrystallized chitosan, present in an amount from about 2% to about 15% by weight, is found to be particularly advantageous. Favorable properties are found related to rapid stoppage of bleeding and bio-absorbability, among other properties. The etherized cellulose matter in the hemostatic composition is maintained in contact with the wound surface for a period of about 20 seconds to about 2-10 minutes. Thus, the time required for clotting and is on the higher side.
Though, each of the above described systems are somewhat effective in the treatment of heavy bleeding, each have drawbacks that prevent their widespread use. Some of the compositions take much more time in clotting, others show adverse effect related to healing and immunogenic reactions due to use of synthetic polymers. Some formulations are highly concentration specific with complexity of manufacturing, upscaling and use. Further, stability, cost effectiveness and ease of administration are a few other aspects which encourage the further research for new formulations for heavy bleeding associated with battlefield and civilian traumatic conditions.
The current invention addresses the unmet medical need of prompt hemostasis especially in case of heavy bleeding using a natural biopolymer combination to reduce arterial heavy bleeding management time/ blood clotting time from 10 minutes to less than 5 minutes in battlefield and civilian traumatic conditions with ease of administer and reduced adverse events with enhanced safety.

OBJECTS OF THE INVENTION

An embodiment of current invention is directed towards providing solution for short term management of hemostasis in humans and animals. It is an objective of one of the embodiment of the present invention to provide a novel Super Porous Inter Polymeric Complex (SPIPC) for short term management of heavy bleeding in battlefield and civilian traumatic conditions including but not limited to venous bleeding and arterial bleeding.
It is another objective of current invention to disclose a novel Super Porous Inter Polymeric Complex (SPIPC) with ionic cross linker.
It is an objective of the one of the embodiment of the present invention to provide novel Super Porous Inter Polymeric Complex (SPIPC) with increased/synergistic efficacy via multiple mechanisms of actions.
It is an objective of one of the embodiment of the present invention to achieve blood clotting during heavy bleeding in battlefield and civilian traumatic conditions/ surgical conditions in within 200 second with tissue sealing.
Yet another objective is to provide natural product based biocompatible, non-immunogenic, easy to use, cost economic, indigenous innovative SPIPC formulations thereof and method of preparation thereof.
It is an objective of the one of the embodiment of the present invention to disclose reproducible processes for the preparation of said Super Porous Interpolymeric complex (SPIPC).
It is an objective of the one of the embodiment of the present invention to prepare highly biocompatible preparation of said Super Porous Interpolymeric complex (SPIPC) for tissue sealing and within 30 second hemostatic time for management of venous and capillary bleeding and within 200 seconds for arterial bleeding caused by traumatic war/ civilian injury/ surgery.
It is an objective of the one of the embodiment of the present invention to provide novel Super Porous Inter Polymeric Complex (SPIPC) based compositions in pharmaceutically acceptable medical device form which are easy to administer, easy to carry, simple to store with stability at harsh conditions of very high / low temperatures.
Another object of one of the embodiment of the present invention is to provide method of manufacture of the novel Super Porous Inter Polymeric Complex (SPIPC) compositions by using green chemistry approach.
Still another object of the one of the embodiment of the present invention is to reduce adverse effects, immunologic reactions and thromboembolic complications related to heavy bleeding during battlefield and civilian traumatic conditions.

SUMMARY OF THE INVENTION

The present invention discloses a novel Super Porous Interpolymeric Complex (SPIPC) comprising ionically cross liked naturally occurring polysaccharides, in pharmaceutically acceptable dosage form, for short term management of heavy bleeding promptly caused due to battlefield injuries or civilian traumatic conditions or surgical conditions. The said SPIPC formulation have remarkable blood clotting efficiency with a clotting time of 30 seconds with complete tissue sealing in venous bleeding and within 200 seconds for arterial bleeding. The present invention further provides reproducible processes for the preparation of said Super Porous Interpolymeric Complex (SPIPC) and formulations made thereof.

BRIEF DESCRIPTION OF THE DRAWINGS

The embodiments herein will be better understood in terms of their characteristics and effectiveness from the following detailed description with reference to the figures depicting various test results:

FIG.1 Describes the difference in hemostatic potential of various components of current invention. Increasing the concentration of calcium chloride adversely affects pliability and flexibility of the product, similarly increasing the concentration of sodium alginate leads to poor cross linking, reduces porosity thereby reducing synergy.

FIG.2 illustrates a comparison of hemostatic potential of product of invention with comparator products.

FIG. 3 illustrates absorption capacity of various versions of product of current invention

DETAILED DESCRIPTION

The embodiments herein and the various features and advantageous details thereof are explained more fully with reference to the non-limiting embodiments that are illustrated in the accompanying figures & tables and detailed in the following description. Reference is made to the accompanying drawings which form a part hereof wherein like numerals designate like parts throughout, and in which is shown by way of illustration embodiments in which the invention may be practiced. It is to be understood that other embodiments may be utilized and structural or logical changes may be made without departing from the scope of the present invention. Therefore, the following detailed description is not to be taken in a limiting sense, and the scope of embodiments in accordance with the present invention is defined by the appended claims and their equivalents. The examples used herein are intended merely to facilitate an understanding of ways in which the embodiments herein may be practiced and to further enable those of skill in the art to practice the embodiments herein. Accordingly, the examples should not be construed as limiting the scope of the embodiments herein.
The description may use the phrases “in an embodiment,” or “in embodiments,” which may each refer to one or more of the same or different embodiments. Furthermore, the terms “comprising,” “including,” “having,” and the like, as used with respect to embodiments of the present invention, are synonymous. Additionally, the various embodiments of the present invention may be combined in any suitable manner.
Current invention discloses a method to control hemorrhage and induce hemostasis in animals and humans in case of trauma/surgery/wound/ external unwanted bleeding condition other than hemophilia.
Blood coagulation or Hemostasis is the cessation of bleeding from a cut or several vessels. When blood is shed, it loses fluid nature in a few minutes and sets into a semisolid jelly. This phenomenon is called coagulation or clotting. A principal method for treating bleeding wounds is to stop the flow of blood by applying pressure with a bandage to facilitate formation of a clot. Currently used wound dressings are often too stiff and too rigid to fit into a narrow space of a cavity wound or, if sufficiently pliable, do not adequately conform to irregular tissues geometries to cause rapid and effective hemostasis, creating an unmet medical need. Therefore, current invention is for topical application of medical device/ product/ formulation/ compositions for efficient immediate hemostasis.
In one embodiment, the site is a bleeding wound at which it is desired to form a blood clot to stop or slow the bleeding. Different variants of medical devices for hemostasis can be applied depending upon the type of wound and severity of flow.
The condition of major hemorrhage is defined as either of these conditions where trauma/ accident/ surgery/ injury results in loss of more than one blood volume (>5 L) in 24 hours or loss of more than 50% of total blood volume (>2.5 L) in 3 hours or loss of more than 150 ml blood per minute. Ideally in any of these conditions, it is currently impossible to save patient, if the patient is an accidental case on road/battel field/civil war/away from immediate medical attention in hospital. The prothrombin time (PT) test measures how well and how long it takes blood to clot. It normally takes about 25 to 30 seconds in minor bleeding. It may take longer if the patient takes blood thinners. Other reasons for abnormal results include hemophilia, liver disease, and malabsorption. Usual coagulation time is 16-17 minutes in glass tube and 19-60 minutes in siliconized tube. Therefore, one of the embodiment of current invention is effective short-term management of bleeding in cases with no bleeding disorder. Also, in patients with impaired coagulation like on aspirin/ antiplatelet drug/ liver impairment/ oral anticoagulants, where there is higher risk of bleeding, medical device of current invention offers effective management.

According to one embodiment, the present invention discloses a novel Super Porous Interpolymeric Complex (SPIPC) comprising ionically cross liked naturally occurring polysaccharides, in pharmaceutically acceptable dosage form, for short term management of heavy bleeding promptly caused due to battlefield injuries or civilian traumatic conditions or surgical conditions. The said SPIPC formulations have remarkable blood clotting efficiency with a clotting time of 30 to 200 seconds. The present invention further provides reproducible processes for the preparation of said Super Porous Interpolymeric Complex (SPIPC) and formulations made thereof.
Chitosan, the N-deacetylated derivation of chitin, has demonstrated hemostatic effectiveness as well as biocompatibility, biodegradability, and anti-bacterial activity. Chitosan is a cationic polymer and has been widely used in the areas of food, cosmetics, biomedical and oral pharmaceutical applications, due to its biocompatibility and other favorable properties. Chitosan has been shown to secure mucoadhesion and hemostasis despite defibrination and anticoagulation. FDA approved topical chitosan hemostats include Celox™ (a granular powder) and HemCon (a chitosan film). Microfibrillar high molecular weight chitosan in the form of sponge is also FDA approved for external use, as puff or non-woven fabric. All these products have own limitations as they do not offer quick hemostasis in heavy bleeding and the time to stop bleeding is usually =5 minutes, have either immunogenicity or cause inflammation and are typically available in high swelling and non-absorbable sponges making their use in effective in heavy bleeding management.
There are three types of bleeding. Capillary bleeding refers to abrasion wounds. There will be oozing from the wound and it usually stops in a few minutes with little assistance. Venous bleeding is more severe than capillary bleeding but is not under pressure like arterial bleeding. It is characterised by steady oozing or running of dark red coloured blood and usually needs hemostatic agents to control. Arterial bleeding is characterised by brighter red blood that may pulsate or spurt as there is a lot of blood coming through and is usually very difficult to control even after use of hemostatic agents and applying pressure. It may spurt again after removal of agent. Therefore, there is an unmet need to control arterial bleeding which is undertaken by current invention.
According to one embodiment, a biodegradable hydrophilic polymer is used in SPIPC which is alginate, preferably sodium alginate. Alginate is a biomaterial that has found numerous applications in biomedical science and engineering due to its favorable properties, including biocompatibility and ease of gelation. Alginate hydrogels have been particularly attractive in wound healing, drug delivery, and tissue engineering applications to date, as these gels retain structural similarity to the extracellular matrices in tissues and can be manipulated to play several critical roles.
According to one of the embodiment of current invention, Sodium alginate improves absorption power of device/ product, provides desired texture and gels with cross linking agent at room temperature without heating, making process energy efficient. In current invention sodium alginate has been used to clot the blood by donating calcium ions from its mannuronic (M) or guluronic (G) groups with a high Ca+ content. The sodium alginate used in current invention has molecular weight in the range of 150kDa to 200KDaltons. A molecular weight higher than 200K Daltons makes device too hard and stiff to apply on wound and has higher immunogenic potential, at the same time sodium alginate with molecular weight less than 150kDa has less mechanical strength and fails to form a stable interpolymeric complex.
According to one of the embodiment use of chitosan for formation of interpolymeric complex is disclosed. Chitosan plain is advantageous over various salt forms of chitosan used in prior arts. Plain chitosan is used in current invention, by the mechanism of crosslinking and has been crosslinked which allows the composition to gelify on coming in contact with water. On the other hand, different salts of chitosan such as chitosan succinate [Vokhidova et al 2017], chitosan pthalate [Aiedeh & Taha], chitosan lactate, acetate and other [Albisetti and Castle] have an ability to dissolve in water, thus to avoid solubilization of chitosan and to cater formation of clot at site of application, crosslinked chitosan would offer a better fluid absorption as well as clot formation than any of its salt forms.
In a preferred embodiment the current invention comprises of chitosan with molecular weight of 15kDa to 20kDa and chain length between 100nm to 1500nm, with biodegradable hydrophilic polymer, sodium alginate and a cross linking agent to provide quick hemostasis in heavily bleeding war wounds and traumatic injuries. In one of the embodiment of current invention mechanism of action of novel Super Porous Interpolymeric Complex (SPIPC) has been described and according to it the chitosan has positively charged quaternary ammonium ions which act on negatively charged red blood corpuscles in super porous interpolymeric complex formed with the help of three ingredients, forms a clot without using any clotting factors such as fibrinogen, prothrombin, thromboplastin, accelerin, globulin etc. This is mainly due to electrostatic forces of attraction in SPIPC between chitosan and other components. Several prior arts have used clotting factors in formulations but use of clotting factors cause allergic reactions. Dextran has been used in a number of preparations which provide a scaffold or powder to stop bleeding, but dextran is related to reducing platelet aggregation and facilitating fibrinolysis. Similarly, gelatine is a collagen use has been disclosed in many prior arts but gelatine is extracted from animals and contains heterogenetic protein which may cause anaphylaxis resulting in fever. Additionally, gelatine based products have slow water absorption capacity which reduce their potential as a haemostatic agent. Kaolin and Bentonite have an ability to immediately halt the bleeding wound but these materials have exhibited thrombogenic effects which raise concern on their in vivo safety. Collagen is another material obtained from animal tissue that promotes blood coagulation by two way mechanism. On one side it stimulates the coagulation cascade, and simultaneously it also acts as a blood thickener by itself getting dissolved in blood and increases its viscosity. However, as in case of gelatine, collagen can also cause infection and anaphylaxis which can reduce the speed of healing process.
In prior arts biocompatible composite microspheres for novel hemostatic use, consisting of carboxymethyl chitosan, sodium alginate, with collagen and in some other use of sodium alginate with gelatin or fibrin have been described, but the efficacy and synergy achieved with formulations of current invention has never been achieved before with any of the prior arts as defined in table 2.
In another preferred embodiment the ionic cross linking agent used to form SPIPC is calcium chloride. An aqueous sodium alginate forms ionic cross-link with divalent cations (i.e., Ca2+) of calcium chloride. Usually this combination is used for gelation process but in current invention, this technique innovatively has been used to form ionic cross linked matrix.
In another reference use of mass ratio of sodium alginate to carboxymethyl chitosan 4:1, mass fraction of CaCl2 2% has been disclosed but in current invention it is observed that increasing sodium alginate concentration beyond 1% alters properties of formulation to undesired levels (Table 1). Therefore, sodium alginate is used in concentration of = 0.5% in the formulations and no thermal or chemical based covalent cross linking is done in current invention. Increase in sodium alginate content from 0.2% led to poor porosity and brittle nature of product formed besides poor linking in SPIPC. Additionally, it is essential to keep calcium chloride concentration below 0.1% level because higher calcium chloride although leads to higher cross linking but porosity, pliability, flexibility, absorption capacity of SPIPC is compromised which ultimately impacts clotting time in heavy bleeding.
Starch in various forms such as biocompatible modified starch of pre-gelatinized starch, acid modified starch, oxidized starch, esterified starch, and cross-linked starch has been reported to acts as a molecular sieve which provides the support for traumatic wound bleeding. The major disadvantage is having very poor water absorbency capacity not more than 1 times its own weight.
According to one of the preferred embodiment, current invention discloses scaffolds for short term management of heavy bleeding wherein the size and dimension can be varied according to need.
Granular hemostatic products have been employed to address the deficiency of current wound dressing for non-compressible wounds, however, these products also have significant drawbacks. Hemostats in the form of granules pose an unacceptable risk in forming emboli. One such form is Microporous Polysaccharide Hemospheres (MPH). The major disadvantages are firstly, the delivery of MPH mainly focuses on local, easy-to-access wound sites but presents some difficulties for effective applications for deep, tortuous wounds, secondly, toxic chemical, is employed to produce a required reaction, the cost of production is expensive, thirdly, the hemostatic efficacy of MPH is not satisfactory in particular for profuse bleeding due to its low hydrophilic capacity and slow water absorption characteristic, fourthly, the adhesiveness of the MPH to tissue is low. Therefore, as per another preferred embodiment of current invention, one of the modified forms is hemostatic granules wherein the size of granules is more than 400micron, applied only on heavily bleeding trauma cases. Size of >400 micron will prevent emboli formation because capillary pore size is = 400microns.
According to yet another embodiment, granular hemostatic device is used in combination with scaffolds, gel and bandages tied tightly to stop blood flow.
As per another embodiment, current invention discloses medical devices in varied sizes of scaffold and powder made with SPIPC technology using plain chitosan of molecular weight of 15kDa to 20kDa and chain length between 100nm to 1500nm, preferably <700nm along with a biodegradable biopolymer sodium alginate of molecular weight of 150kDa to 200kDa and chain length between 200nm to 1200nm, preferably <1000nm and a ionic cross linking agent using green chemistry approach such that the formulation formed thereof provide short term management of bleeding in 30 to 200 seconds, wherein short term management means removal of all such devices once bleeding is managed and the patient is within proper medical attention. It is important to mention that all the components are biodegradable and the objective is to provide an immediate heavy bleeding management solution which can control bleeding up to of arterial level within 200 seconds of application of one or more of medical devices of current invention.
According to yet another embodiment, the ratio and concentration of each component is critical in making SPIPC of current invention such that the formulations/ devices made thereof have capacity to absorb between 10 to 30 times volume of their own weight without increasing in size. This feature is critical in heavy bleeding management because it does not allow undue suction of blood from arteries/veins/ capillaries and absorbs only the oozing/ oozed out blood only, reducing clotting time efficiently.
According to one preferred embodiment chitosan used is deacetylated in a concentration of 1000mg to 10000mg, preferably between 1000 to 5000mg per 100ml of the formulation is added to provide best synergistic clotting time.
According to another embodiment sodium alginate in a concentration of 100mg to 500mg, preferably between 125 to 250mg per 100ml of the formulation is added to provide the most super porous interpenetrating network.
According to yet another embodiment the concentration of cross linking agent calcium chloride is between 5mg to 50mg, preferably between 10 to 30mg per 100ml of the formulation is added to provide rigidity to the networking complex and assist in lowering clotting time.
According to yet another embodiment the ratio of hydrophilic polymer to cross linking agent is between 6:1 to 10:1, preferably 8.3:1.
According to yet another embodiment, the products of current invention have chitosan as main ingredient in a range from 0.5% to 5%w/v, preferably from 1% to 3%w/v, sodium alginate in range of 0.1% to 1.0 %w/v, preferably = 0.25%w/v and calcium chloride in range of 0.01% to 0.1%w/v, preferably = 0.05%w/v, wherein the compositions made thereof have pH values in range of 5.5 to 10, have swelling index in range of 1 to 5.0 and moisture content in range of 5-15%.
Additional absorbant material may be combined prior to, during or subsequent to current formulations being formed. The combining of absorbant material with current invention may be performed by impregnating, suffusing, coating or dispersing the absorbant material. In another embodiment, the absorbent material may be soaked in prior to drying/lyophilization.
The compositions and formulations made thereof have fluid penetration of = 0.5cm indicating a high absorption power which is required to control heavy bleeding. As defined in table 3 absorption capacities of different variants is 14 to 30 times their own weight and is achieved within 5 seconds and is maintained after that.
According to yet another embodiment, formulations/ devices of current invention are stable at wide range of temperature range from -20 degree celcius to +50 degree celcius and have physical properties of pliability, flexibility, moldability, and curling for efficient short term management of heavy bleeding within 30 to 200 seconds.
The mean thickness of the scaffolds/ devices can be varied according to specific application from 2mm to 30mm for example bleeding control in dental surgeries would require a device/ scaffold as small as 2mm3 whereas in battle field injuries where part of the abdominal cavity/ any other organ is blown off would require a scaffold/ device to fill the cavity and can vary in sizes and can be customized. Therefore, the area (length and width), volume (including height) of the hemostatic products of scaffold nature of current invention can vary and be adjusted.
According to yet another preferred embodiment of current invention, it is desired that a granular form of SPIPC be employed where the particle size of granules is not less than 400micron. Further, formulation is processed such that granular form prevents emboli formation and reduces risk of thromboembolism, accommodate good flow properties. Additionally, by virtue of biodegradable nature of all the components used in system, they would not pose any threat to the patient.
The treatment of penetrating wounds such as bullet wounds or some wounds from shrapnel is problematic. This is due to the difficulty in placing a hemostatic product and/or therapeutic agents at the actual site of injury, which includes an area that is well below the body surface and difficult or impossible to access using conventional techniques. One of the embodiment of current invention is to provide products that lead to drastic reduction in clotting time which is critical for battlefield/ road side traumatic situations. Another advantage of current invention is stability, extended shelf life, resistance to high and low pressure, resistance to high temperature (up to 50° C) and low temperature (down to -20° C), convenient storage, and physical stability. Therefore, it may also be employed as a hemostatic material for the military, emergency, and first-aid uses. Particularly, it can be adapted for extreme environmental conditions such as desert areas, polar regions, alpine areas, outer space, and underwater probes. Another embodiment of current invention is that products offer physical properties of pliability, flexibility, moldability, and curling. These can be adapted for wound surfaces with various shapes, sizes, and features, such as deep and irregular anatomical wounds, organ physiologies, both inside and outside the lacuna surface or open surgery.
According to the most preferred embodiment of current invention the formulations are made up of chitosan, sodium alginate and calcium chloride where the components are present in ratio of 150:10:1, preferably in range of 50:10:1 to 125:10:1, wherein the products have coagulation time of less than 90 seconds for capillary and venous bleeding and up to 200 seconds for arterial bleeding.
According to yet another most preferred embodiments, current invention forms super porous ionic polymeric complex using very low concentrations of polymers which are ionically cross linked with calcium chloride wherein the weight ratios are critical for achieving absorption capacity up to 30 times the own weight of formulations and present in the ratio of chitosan: sodium alginate: calcium chloride in range of 125:10:1 to 50:10:1, where the weight of sodium alginate is = 0.2% w/v by weight and increasing concentration beyond this affects porosity and hence absorption capacity of formulations. Similarly, amount of calcium chloride is = 0.02% w/v by weight and increasing the amount of calcium chloride makes product brittle and increasing the amount of chitosan beyond 3% w/v by weight results non-flexible product with affecting tissue adhesion properties and lowers hemostatic potential. A very high molecular weight polymer with very big chain length >1000nm interferes in complex formation and thereby the efficacy, performance and processing of SPIPC is badly impacted.
SPIPC, Super Porous Inter Polymeric Complex formed in current invention has multiple advantages and is advancement in technology through ionic and hydrogen bonding. SPIPC is highly dependent on the concentration of components. Super porous interpolymeric complex formed due to hydrogen/ ionic bonding forms a networking structure which has high absorption capacity, flexibility and excellent porosity which allows stability even at extreme temperature conditions and has very low clotting time by virtue of synergy of the components used in SPIPC processing. Additionally, chitosan products usually become unstable due to polymeric chain scissation and this is prevented by SPIPC technology. Further, very fast and enhanced adhesion due to SPIPC technology leads to concentration of erythrocytes and platelets leading to platelet adhesion, aggregation and coagulation resulting in enhanced clotting, leading to faster onset of action. Furthermore, high mucosal binding capacity due to interplay of charges enhances basic mucoadhesive and polycationic properties of the product with multitude of adhesive effect thereby reducing quantity required for hemostasis.
According to one embodiment, the hemostatic mechanism of current invention is still under study, but is postulated to be via vasoconstriction and the rapid mobilization of red blood cells, clotting factors, and platelet to the site of the injury due to charged interactions between components of SPIPC and blood/tissue. Formulations significantly enhance both platelet adhesion and aggregation, which may account for the interaction of platelets with damaged tissues and promoting wound healing effect in addition to hemostasis. SPIPC sticks well to damage tissues to plug the bleeding site as the material binds to the surface of red blood cells.
According to one of the most preferred embodiment, super porous inter polymeric complex technology is used for short term instant management of heavy bleeding in traumatic, surgical conditions in human and animals where formulations comprise of sodium alginate of molecular weight 150kDa to 200KDa with chain length of 200-1200nm, in weight range of = 0.2% w/v to form
ionic cross linked matrix with calcium chloride which is present in range of = 0.02% w/v along with chitosan which is dispersed in above said matrix and has molecular weight 15kDa to 20kDa with chain length of 100-1500nm, is present in weight range of 0.5% to 5%w/v, wherein the said super porous inter polymeric complex has absorption capacity of 10-30 times its own weight, offers hemostasis on 30 to 200 seconds, has pliability, flexibility, moldability, and curling properties to enable instant hemostasis.
According to yet another preferred embodiment, the process includes mixing sodium alginate with calcium chloride to prepare matrix after dissolution in 90% of total amount of water to be used for formulation at temperature between 55-60º C with continuous air purging to prepare solution A. Disperse desired quantity of chitosan slowly in solution A along with 1% glacial acetic acid to form a clear gelling consistency without foaming with continuous stirring and air/ gas purging such that temperature for resultant solution B reaches around 30ºC. Check pH and adjust if needed with volume adjustment with remaining water. Process the solution B for lyophilization for scaffold in desired molds or in trey drier for powdered granules. The mixing steps are critical and cannot be changed to achieve desired porosity in SPIPC complex. Medical devices such formed are sterilized by gamma and/or ETO or other radiation techniques.
Above disclosure describe a brief overview of making using the invention and sets forth the best mode contemplated by the inventor for carrying out his invention but is not to be construed as limiting. Various modifications and variations of the described method and system of the invention will be apparent to those skilled in the art without departing from the scope and spirit of the invention.
Further detailed embodiments, examples and experiments in the detailed description would be evident from the Complete Specification of this provisional specification which would be filed after this filing.

Claims:

1. A biodegradable hemostatic medical device and formulations made thereof for short term instant management of heavy bleeding in traumatic, surgical conditions in animals and humans;
wherein the formulations are made with super porous inter polymeric complex (SPIPC) technology;
wherein SPIPC comprise of two naturally occurring biopolymers;
wherein one of the said biopolymer sodium alginate of molecular weight 150kDa to 200KDa;
wherein the said biopolymer is combined with ionic cross linking agent in ratio of 10:1;
wherein SPIPC comprise of another biodegradable polymer chitosan in molecular weight 15kDa to 20kDa;
wherein the ratio of chitosan: sodium alginate: cross linking agent is in range of 125:10:1 to 50:10:1;
wherein the said formulations achieve hemostasis in 30 to 200 seconds.

2. According to claim 1 wherein, the said ionic cross linking agent is calcium chloride;
wherein calcium chloride is present in 0.01-0.05%w/v of the total weight of formulation.

3. According to claim 1, super porous interpolymeric complex accelerates blood clotting and tissue adhesion;
wherein chitosan in range of 0.5%-5%w/v.

4. According to claim 1,
wherein sodium alginate is present in 0.1%-0.5%w/v of the total weight of the formulation.

5. According to claim 1 and 2, super porous inter polymeric complex for management of heavy bleeding;
wherein the said ionic cross linked matrix forms stable complex with high porosity;
wherein the said complex is stable at extreme temperature conditions of -20 to 50º C;
wherein the said complex has absorption capacity of 10-30 times its own weight.

6. According to claim 1 and 5, super porous inter polymeric complex for management of heavy bleeding;
wherein formulations additionally comprise of absorbant materials.

7. The formulations of claim 1 using super porous inter polymeric complex technology for short term instant management of heavy bleeding in traumatic, surgical conditions;
wherein, the said formulations comprise of sodium alginate of molecular weight 150kDa to 200KDa with chain length of 200-1200nm, in weight range of = 0.2% w/v;
wherein the said sodium alginate forms ionic cross linked matrix with calcium chloride;
wherein the weight of calcium chloride is in range of = 0.02% w/v,
wherein chitosan in dispersed in above said matrix has molecular weight 15kDa to 20kDa with chain length of 100-1500nm;
wherein the said chitosan is present in weight range of 0.5% to 5%w/v;
wherein the said super porous inter polymeric complex has absorption capacity of 10-30
times its own weight;
wherein the said complex offers hemostasis on 30 to 200 seconds;
wherein the said complex has pliability, flexibility, moldability, and curling properties to enable instant hemostasis in animals and humans.

8. The formulations for hemostasis of claim 1 are processed as per following steps:
a. mixing specific ratios of sodium alginate with calcium chloride to prepare matrix after dissolution in 90% of total amount of water to be used for formulation at temperature between 55-60º C with continuous air purging to prepare solution A;
b. disperse desired quantity of chitosan slowly in solution A along with 1% glacial acetic acid to form a clear gelling consistency without foaming with continuous stirring and air/ gas purging such that temperature for resultant solution B reaches around 30ºC;
c. check pH and adjust if needed with volume adjustment;
d. process the solution B for lyophilization for scaffold in desired molds or in trey drier for powdered granules.

9. The process of preparing SPIPC formulations additionally involves sterilization by radiation.