2. HEMA LIMIT Matrix & Powder OXIDISED-CELLULOSE BASED HAEMOSTATS

3. HEMA LIMIT Matrix OXIDISED-CELLULOSE BASED HAEMOSTATS

4. HEMA LIMIT matrix is a sterile haemostatic preparation based on oxidised cellulose available in flat form with textile structure. Content: Carboxycellulosum 100% (oxidized cellulose) Sterile HEMA LIMIT matrix OXIDISED-CELLULOSE BASED HAEMOSTAT

5. What is it used for Excellent haemostatic agent to professionally arrest capillary bleeding, or bleeding from parenchymatous organs and resection areas at surgical procedures. It shall be used to stop bleeding when other haemostatic procedures are not applicable. HEMA LIMIT matrix OXIDISED-CELLULOSE BASED HAEMOSTAT

6. How is it made HEMA LIMIT is produced by selective oxidation of high-quality cotton material (99% of cellulose content at minimum). The process selectivity lies in the fact that predominantly alcoholic group on 6th carbon of basic building unit is oxidized and carboxyl is formed (- COOH), whose content is maintained at 16 – 24 volume percentage according to USP. From the chemical point of view it is polyanhydroglucuronic acid (used for HEMA LIMIT matrix), whose acidity is decreased by neutralization to calcium salt (used for HEMA LIMIT powder form). As free carboxyl group is a carrier of oxidized cellulose bactericidal effect, only a part of those groups is calcium bound, residual ones are free. HEMA LIMIT matrix OXIDISED-CELLULOSE BASED HAEMOSTAT

7. How does it work HEMA LIMIT has a significant effect on starting the haemocoagulation process, and accelerates the blood coagulation in several ways. While applied, Factor VII is activated as well as the thrombocyte activation is initiated by tissue factor. Due to anion active characteristics of oxidized cellulose, HEMA LIMIT is able to form complex polymers with compounds such as fibrinogen or haemoglobin, therefore fibrinogen polymerization is speeded up. Calcium ions (powder form) are used during protein complex fixation on cell membranes, in particular thrombocytes and endotel cells. Higher Ca2+ ion concentration stabilizes activated Factor V and speeds up HEMA LIMIT matrix OXIDISED-CELLULOSE BASED HAEMOSTAT

8. How does it work Factor XIII activity resulting in fibrinogen network stabilization which is therefore able to create sufficiently organized structure for fibroblast growth and cicatrix formation. During coagulation process Ca2+ ions partially participate in thrombocyte adhesion to collagens of exposed wound, and also show partial analgesic effect. This is considered to be due to ion blockage effect on autonomous nerve-endings. HEMA LIMIT matrix OXIDISED-CELLULOSE BASED HAEMOSTAT

9. Special Characteristics (Features) Its indisputable advantage is the possibility of fixing the material by stitching. Due to the content of carboxyl groups (16-24%) that have the proven features of being bactericidal and bacteriostatic, and further due to the increased fibroblast activation initiated by the active substance, the healing process in the application area is more rapid. Therefore, HEMA LIMIT matrix shall be used for faster healing of non-responding wounds such as lacerations, leg ulcers, decubitus, bed sores etc. HEMA LIMIT matrix OXIDISED-CELLULOSE BASED HAEMOSTAT

10. Areas of Application/Clinical Experience It is suitable for use in: * general surgery and digestive surgery, * plastic surgery, * orthopaedic surgery, * neurosurgery, * thoracic surgery, * vascular surgery, * gynaecology, * urology and all other branches of surgery, traumatology and stomatology. In dental praxis, the preparation shall be also used to arrest prolonged post-extraction capillary bleeding. HEMA LIMIT matrix OXIDISED-CELLULOSE BASED HAEMOSTAT

11. Areas of Application Neurosurgery Haemostasis (epidural) after tumor extirpation. Cerebral parenchyma haemostasis. Application: * Bleeding from cranium vault at craniotomy and Dura mater rupture * Bleeding from spongy layer, e.g. after trephination * Cranial Dural haemorrhage * Dural bleeding after tumor extirpation * Cerebral parenchyma bleeding HEMA LIMIT matrix OXIDISED-CELLULOSE BASED HAEMOSTAT

12. Areas of Application Thoracic/vascular surgery Bleeding / madescent prophylacy caused by suture canals after anastomosis. Relief at haemostasis of wounded or resected parenchyma. Application: * Bleeding which might occur during surgical procedures with extracorporeal circulation * At pericardectomy after removing pericardium and pleura adhesion * Bleeding from suture canals, i.e. after vascular anastomosis * At thoracic wall surgery * Bleeding from pulmonary parenchyma after wound or resection treatment of bleeding from tumor matrix * Epicardium bleeding * After breaking adhesion round heart HEMA LIMIT matrix OXIDISED-CELLULOSE BASED HAEMOSTAT

13. Areas of Application Plastic Surgery Support at graft fixing, stopping madescent of donator graft removal spots. Stopping madescent and support of granular tissue healing. Application: * Cosmetic surgery * Complicated reconstructions at: Palate reconstruction Post traumatic skin reactions Burns Bleeding from donator graft Removal spots * Bleeding from spongy tissue * Bleeding from oral cavity mucous membrane after tumor resection * Bleeding from spongy tissue HEMA LIMIT matrix OXIDISED-CELLULOSE BASED HAEMOSTAT

14. Areas of Application Soft Tissue Surgery Haemostasis of gall bladder matrix after holecystectomy. Supporting preparation for shopping madescent after liver/spleen lesion. After biopsy as well. Application: * On lesions in liver after resections and cholecystectomies * Supporting preparation at liver rupture * Liver biopsy * Rectal surgery * After breaking adhesion Spleen capsule ruptures Thyroid gland surgery HEMA LIMIT matrix OXIDISED-CELLULOSE BASED HAEMOSTAT

15. Areas of Application Gynaecology Applied at hysterectomies. Haemostasis after removing cervical carcinoma. Application: * Bleeding at surgery on uterus and cervix (conisation), breaking adhesion in lesser pelvis and Douglas area * Tumor bleeding treatment at hysterectomies * After removing cervical carcinoma HEMA LIMIT matrix OXIDISED-CELLULOSE BASED HAEMOSTAT

16. Areas of Application Urology Stopping difficult bleeding/madescent after prostatectomy. Parenchyma haemostasis. Application: * Tumor bleeding treatment * At hysterectomy * After removing cervical carcinoma * After removing fibroids HEMA LIMIT matrix OXIDISED-CELLULOSE BASED HAEMOSTAT

17. Areas of Application Stomatology Application: * At treating postextraction wounds. * Haemostasis at maxillofacial surgeries. HEMA LIMIT matrix OXIDISED-CELLULOSE BASED HAEMOSTAT

18. HEMA LIMIT matrix OXIDISED-CELLULOSE BASED HAEMOSTAT Dosage/Method of Use After opening the outer/secondary packaging, take out the inner/primary packaging. This primary packaging is sterile and contains the chosen preparation of HEMA LIMIT matrix. The preparation could be adjusted / cut by sterile instruments to the requested application size and then it could be applied onto the bleeding area.

19. HEMA LIMIT matrix OXIDISED-CELLULOSE BASED HAEMOSTAT Dosage/Method of Use The material saturated with blood forms a brownish layer that shall not be removed - it will be fully absorbed. The haemostatic effect is immediate; the full haemostasis is achieved within 2 minutes. Another layer could be applied in case the blood still oozes through. The material could be stitched to the tissue if recommended by surgeon.

20. HEMA LIMIT matrix OXIDISED-CELLULOSE BASED HAEMOSTAT Packaging The material is packed into double sterile packaging. The primary/inner packaging is a silver/black foil having a peel-effect on one side to enable an easy opening. The secondary/outer packaging shall be one-side transparent, with a peel-effect on one side for an easy opening. Sterility Sterilized by gamma irradiation

21. HEMA LIMIT matrix OXIDISED-CELLULOSE BASED HAEMOSTAT Storage Conditions Store in a dry room at room temperature (preferably between 5-25 o C). For a long-term storage we recommend to store the material below 20 o C. Do not expose to direct light.

22. HEMA LIMIT matrix OXIDISED-CELLULOSE BASED HAEMOSTAT Dimensions Individual pieces of active textile matrix are always with a given width that remains unchanged whereas its length could be adjusted according to specific demands of customers. Dimensions Provided 50 x 50 mm 50 x 100 mm 100 x 100 mm 50 x 70 mm 50 x 350 mm 100 x 200 mm

23. HEMA LIMIT matrix OXIDISED-CELLULOSE BASED HAEMOSTAT HEMA LIMIT matrix in brief is destined to arrest capillary and minor venous bleeding and bleeding from parenchymatous organs and resection areas, at any kind of surgical interventions could be applied into cavities (after extirpation of tumours) as well dental praxis the haemostatic effect is almost immediate, the full haemostasis is achieved by 2 minutes after application is fully absorbed by 12 - 72 hours, depending on the application form and wound extent is entirely eliminated from the body within 7 - 21 days, leaving no deposit behind in tissues and cells is biocompatible, biodegradable, non-acidifying haemostatic preparation of natural origin

24. HEMA LIMIT matrix OXIDISED-CELLULOSE BASED HAEMOSTAT HEMA LIMIT matrix in brief is hypoallergenic - no sensitive features have been reported, no immune-reactions have been initiated, even after repeated application is well tolerated by the organism and has a significant effect on healing process in wounds causes no irritating reactions on the application area, no granuloms are formed has bactericidal and bacteriostatic features due to the presence of carboxyl groups no adverse effects as such have been reported is an ideal alternative to bovine fibrins and collagens

25. HEMA LIMIT Powder OXIDISED-CELLULOSE BASED HAEMOSTATS

26. HEMA LIMIT Powder OXIDISED-CELLULOSE BASED HAEMOSTAT HEMA LIMIT powder is a haemostatic preparation in a STERILE powder form, with the active substance based on oxidised cellulose and is destined to arrest capillary and minor venous bleeding and bleeding from parenchymatous organs at surgical interventions. Content: Calcium hydrogencarboxycellulosum (hydrogencalcium salt of oxidised cellulose) 100 %

27. HEMA LIMIT Powder OXIDISED-CELLULOSE BASED HAEMOSTAT Special Characteristics Due to the content of carboxyl groups (16-24%) and calcium ions, it supports the biological healing process, and has the proven features of being bactericidal and bacteriostatic.

28. HEMA LIMIT Powder OXIDISED-CELLULOSE BASED HAEMOSTAT Areas of Application/Clinical Experience It is suitable for use in: * general surgery and digestive surgery, * plastic surgery, * orthopaedic surgery, * neurosurgery, * thoracic surgery, * vascular surgery, * gynaecology, * urology and all other branches of surgery, traumatology and stomatology. In dental praxis, the preparation shall be also used to arrest prolonged post-extraction capillary bleeding.

29. HEMA LIMIT Powder OXIDISED-CELLULOSE BASED HAEMOSTAT Dosage/Method of Use After opening the outer packaging and undoing the cover apply a thin layer of powder on to a bleeding area by repeatedly pressing the sides of the bottle. The powder that does not get saturated with blood, is recommended to be removed. The powder layer saturated with blood becomes red to dark brown that need not be removed - it will be gradually absorbed. In case of an application into a cavity or small area, use the applicator by fixing it on to the sprinkler.

30. HEMA LIMIT Powder OXIDISED-CELLULOSE BASED HAEMOSTAT Dosage/Method of Use If the blood still oozes slightly through, but the powder is not washed off, apply another layer, or if possible press the layer down by sterile devices until the haemostasis is initiated. If needed for a superficial treatment, use a cushion plaster or dressing. If the powder is washed off by blood, it indicates an inappropriate use as the preparation is destined to control non- pressure bleeding only.

31. HEMA LIMIT Powder OXIDISED-CELLULOSE BASED HAEMOSTAT Packaging HEMA LIMIT powder is packed into a triple sterile packaging that guarantees a perfect sterility. The primary/inner packaging shall be a plastic bottle with a sprinkler and a cover, with the added applicator for use to cavities or precise application. The secondary/outer packaging shall be one-side transparent, with the peel-effect for an easy opening and the additional outer packaging shall be one-side transparent, with the peel-effect for an easy opening. The packaging contains 3g or 5g of active substance (according to customers requirements).

32. HEMA LIMIT Powder OXIDISED-CELLULOSE BASED HAEMOSTAT Packaging Provided Hemalimit powder 3grams Hemalimit powder 5grams Sterility Sterilized by gamma irradiation

33. HEMA LIMIT Powder OXIDISED-CELLULOSE BASED HAEMOSTAT Storage Conditions Store in a dry room at room temperature (preferably between 5-25 o C). For a long-term storage we recommend to store the material below 20 o C. Do not expose to direct light.

34. HEMA LIMIT Powder OXIDISED-CELLULOSE BASED HAEMOSTAT HEMA LIMIT Powder in brief efficacious haemostat based on hydrogen calcium salt of oxidised cellulose exhibits immediate haemostatic effect, the full haemostasis is achieved within 2-3 minutes after application it is destined to arrest capillary and minor venous bleeding and bleeding from parenchymatous organs and resection areas at any kind of surgical interventions in ambulances and clinical praxis. It could be applied into cavities (after extirpation of tumours) as well as during endoscopy interventions or dental praxis. fully absorbed in 12 - 72 hours depending on the type of form applied and wound extent entirely eliminated in 7 - 21 days, there are no deposits left behind in tissues and cells

35. HEMA LIMIT powder OXIDISED-CELLULOSE BASED HAEMOSTAT HEMA LIMIT powder in brief hypoallergenic - it exhibits no sensitising properties and causes no adverse immunoreaction of organism even in case of recurrent application bio-compatible, bio-degradable, non-acidifying haemostat of natural origin well tolerated by the organism and it encourages wound healing where applied presents no risk of irritating the wound, no granulomas are formed has a bacteriostatic and bactericidal effect, the epithelisation process is accelerated