Expandable & Soluble Chitosan Sponge

Product composition and mechanism of action

Chitosan is the N- deacetylation product of Chitin, the natural glucidamin extracted from the shells of shrimp and crab using modern bioengineering technique.

Chitin is the only natural high molecular polymer carrying positive charges in the natural world. It belongs to linear chain glucidamin. The scientific name of it is: [(1,4)-2- acetamido -2- deoxidation -β-D-glucose], the molecular formula is (C₈H₁₃NO₅)_n, and the monomers are connected by β(1→4)glycoside bond. The chemical structure of chitin is very similar to that of cellulose existing in the plants so chitin is a kind of animal fiber. It will turn into chitosan if 55% deacetamido of chitin is fulfilled. The final hydrolyzate of chitosan is glucosamine.

Chitosan has strong affinity with human cells and it can be broken down by internal enzeme and then absorbed. It doesn’t have toxicity and side effects to the human body. Meanwhile, the biological function of chitosan such as: antibiosis and bacteriostasis, haemostasis, promoting wound healing, preventing tissue coagulation. So it has become the excellent biomedical, pharmaceutical materials and has been extensively developed and applied.

Soluble haemostatic material (Expandable & Soluble Chitosan Sponge) is sponginess preparation made of natural biological material-chitosan by advanced craft. The main mechanism of actions are:

First: Chitosan is the only polysaccharide carrying positive charges, so it can combine with erythrocyte, white blood cell and platelet that carries negative charges to achieve thrombosis.

Second: The sponginess preparation has expandability after absorbing water. So it can evenly and softly oppress the wound oozing at nasal cavity, nasal sinuses and dental alveoli after tooth extraction.

Third: N-acetyl glucosamine and glucosamine glycal, the subunit of the repeated monomer of this product are the main composition of mucosa epithelium, which can activate the macrophage and mucosa epithelium at the wound to promote local mucosa healing.

Fourth: This product is dissoluble and uniform chitosan gel will be formed on the oozing wound to protect wound and stop bleeding.

Research of clinical application

First: Haemostatic effect

Soluble haemostatic material (Expandable & Soluble Chitosan Sponge) has been applied to 1056 patients for haemostasis in rhinopolypus endoscope surgery, nasal septal construction, turbinectomy, nasal mucosa, tooth extraction from 2004 in Affiliated Renji Hospital of Shanghai Second Medical University, Affiliated Ninth People’s Hospital of Shanghai Second Medical University, Qilu Hospital of Shandong University, First People’s Hospital of Hangzhou City and Shandong Qiaolian Hospital. No adverse effects such as rejection, inflammation and hypersensitive happened. The material can dissolve by itself and be absorbed or discharged. It has the characteristics of good biological compatibility, safety, obvious haemostatic effect and it’s convenient to use.

Second: Physical and biological characteristics

Soluble haemostatic material (Expandable & Soluble Chitosan Sponge) is a new haemastatic material with high expansion coefficient and solubility made of natural glucidamin through modern bioengineering technique. It not only has fine clinical haemostatic effect but only has biological functions such as bacteriostasis, promoting wound healing and preventing conglutination. Meanwhile, the other characteristics of this product such as easy solution, short detention time and soft reduce all kinds of clinical disorders greatly when using haemostatic materials.

Table one: The physical & chemical characteristics of different haemostatic materials

Table two: Biological characteristics of different haemostatic materials

Related basic research

First: the haemostatic effect of Chitosan

Klokkevold observed the haemostatic activity of chitosan through experiements. They made incisal opening on both sides of rabbit tongue. One side was treated using chitosan and the other side was used as control. They observed that the haemostatic function on the rabbit tongue accepting chitosan treatment improved a lot, and the bleeding time shortened 32% compared with that of control group. For rabbit platelet functional disturbance model made through platelet functional antagon-Epoprostenol, the bleeding time shortened 56% compared with that of control group, which showed the haemostatic activity of chitosan is very strong.

The haemostatic mechanism of chitosan is achieved through promoting the red cell agglutination. The repelling action among the red cells is one of the important reasons that the red cells can’t agglutinate. The net negative charges on the cellular membrane of red cells are the resources of inter-repellant. These negative charges come from nueaminic acid residue on the surface of cellular membrane. The mechanism of haemostatic function is achieved through the interaction of the positive charges on the chitosan and the receptor containing nueaminic acid residue on the surface of cellular membrane. Obviously, this agglutination doesn’t rely on the normal grume pathway, so it won’t be affected by anticoagulant therapy and other coagulation disorders.

Second: the effect of Chitosan for restraining microorganism growth

Just as other polysaccharide, Chitosan contains highly active functional groups in its complex spatial structure, which appears characteristics similar to that of bacteriophage and have immunological regulation function within the body.

The experiments show the bacteriostasis function of chitosan is related to its molecular weight. The researches prove the antibacterial activity of chitosan increases with the decrease of molecular weight. At density of 500×10, the bacteriostasis effect of chitosan with molecular weight of 13000 is (+), and that of chitosan with molecular weight of 5000 is (++), and that of chitosan with molecular weight of 3000 is (+++), and that of chitosan with molecular weight of 1500 is (++++).

The bacteriostasis function of chitosan is achieved by two biochemical process:

Contacting bacteriostasis - chitosan is a kind of natural high polymer carrying strongpositive charges and will combine with the acylneuraminate of microorganism phospholipins to restrain the vital movement of microorganisms.

Expanding bacteriostasis - chitosan oligosaccharide penetrates into the cells of microorganism and restrains the transcription of genetic information to prevent cell division and multiplication.

Growth result of strain with different density of chitosan

☆1% acetic acid solution(control group); (-) the medium is transparent; (+) the medium is turbid

Third: the effect of Chitosan for promoting wound healing

Su covered the full-thickness wound on the dorso skin of guinea pig using chitosan membrane. On the 10^th day, he discovered the wound was smaller than that of control group (covered by gauze), which showed newly regenerated cells had formed. On the 20^th day, folliculus differentiation had occurred, however, in the control group, newly-regenerated cells appeared on the 15^th day. Histological examination discovered large amount of polymorphonuclear leucocytes appeared in the treatment group, while in the control group, only small amount of monocytes appeared. This shows chitosan can promote wound healing and increase the tensile strength of the healed skin.

The mechanism of chitosan for promoting wound healing: 1. The subunit of the repeated monomer of chitosan, N-acetyl glucosamine and glucosamine glucal are the main compositions of epithelium mucosa, which can activate the macrophagocyte and epithelium mucosa at the wound to promote local mucosa healing; 2. Promote epithelium and vascular endothelial cell regeneration; 3. Promote fibroblast migration; 4. Induce collagen deposit and arrangement in order to promote the construction of collagen tissue and structure remodeling.

Fourth: the effect of chitosan for preventing tissue conglutination

Large amount of animal experiment and clinical application proved that: chitosan can effectively prevent muscle tendon, joint conglutination and tissue conglutination after belly cavity surgery. The main mechanisms are: 1. Restrain the growth and proliferation of fibroblast selectively to obstruct the origin of collagen fibers; 2. Effective haemostatic function to reduce organization of hematoma and the invasion of fibroblast; 3. Chitosan as high-molecular biomaterial will form biomembrane among damaged tissues which has hydrophilism and can last long enough to act as biological barrier among the tissues. Nutrition can go through this biomembrane 
Product Characteristics

This soluble haemostatic material (Expandable & Soluble Chitosan Sponge) is sponginess preparation with all kinds of specifications so that can be used to different wounds.

Physical & chemical characteristics

1.       Expansion coefficient ≥ 100%

2.       Absorption rate ≥ 200%

3.       Solubleness: 24-96 hour

4.       pH: 7.5±0.5

5.       Loss on drying: dry the product to constant weight at 105⁰C, the loss of weight should not be larger than 30%

6.       Identification reaction:  pheno-sodium reaction

7.       Content of heavy metal ion: ≤0.002%

Biological characteristics

Biological safety: without haemolyticus, without cytotoxicity, without mucous membrane irritation reaction.

Biodegradation: soluble haemostatic material (Expandable & Soluble Chitosan Sponge) has complete biodegradation, mainly through the following two ways:

1)      Body fluid dissolve; 2) Muramidase degradation. The final product after degradation is amino glucose.

Indications

This soluble haemostatic material (Expandable & Soluble Chitosan Sponge) can be extensively applied for wound blood oozing of accessory nasal cavity and nasal cavity caused by injuries or operations. Application: all kinds of endoscopic sinus surgery, nasal septal construction, turbinectomy, nasal mucosal bleeding, palatorrhaphy and exodontias.

Announcements

1.       This product is disposable sterile product, so subpackage and cross employment between patients are forbidden.

2.       Products with broken package are forbidden to use.

3.       This product is mainly applied for the wound blood oozing caused by capillary damage. For wound bleeding caused by the rupture of great vessels, other measures should be adopted, such as: ligation, saturation and electric coagulation. And then this product can be used.

4.       If patients have other systemic coagulation disorders, systemic treatment methods should be adopted based on the etiopathogenisis.

Method for Use

Products with different specifications and shapes are selected by doctors with expertise based on the detailed condition of the patients. No special instrument is necessary because the usage is very simple.

Absorb/wipe the oozing blood on the wound using attractor/sterile tampon, then take out the product and cut to suitable size according to the size of wound and then fill/cover the wound.

The product can dissolve or depart from the wound by itself, so it is not necessary to take it out.

Product Features

Good biological safety

This product is made of natural native materials without toxin, irritation and hypersensitive reaction.

Reliable haemostatic effect

Chitosan is the only polysaccharide carrying positive charges in the natural world, and it will combine with the erythrocyte that carries negative charges and then thrombosis will happen. This process doesn’t rely on the normal grume pathway, therefore this process doesn’t affected by anticoagulant therapy and other coagulation disorders.

Multiple biological function

Has multiple biological functions such as bacteriostasis, promoting mucosa tissue healing and preventing tissues conglutination.

Convenient clinical application

This product is soft and can dissolve easily and the retention time in the body is short, which in all decrease kinds of clinical disorder greatly. The product can dissolve or depart from the wound by itself, so it is not necessary to take it out.