USOO5997.876A United States Patent (19) 11 Patent Number: 5,997,876 Shikhashvili et al. (45) Date of Patent: Dec. 7, 1999

54) BURN AND WOUND OINTMENT from mint and one other plant, and herb mixture edible oil extract, abstract, Make, Jan. 1995. 76 Inventors: Nino Shikhashvili, Building 5, Apt. 77, Mukhiani Settlement 3, Tbilisi, Ga. Database Derwent Publications, No. 95-342794, Purakhina 38072; Zurab Darsavelidze, Building et al. Anitbacterial cream for perSona Saintary use contains 13, Apt. 61, Gldani Settlement 8, dry extracts of St. John's Wort and bur marigold, yarrow Tbilisi, Ga. 38012 grass and calendula flowers, liquorice root, Sea buckthorn 21 Appl. No.: 09/180,635 berries, and ointment, Mar. 1995. Database Derwent Publications, No. 96–107601, Prepara 22 PCT Filed: May 8, 1997 tion of dermatology cream type cerate comprises thermo 86 PCT No.: PCT/GE97/00001 Stated agitated blending of plant fractions, e.g. Chelidonium majus and Plantago lanceolata, Soria Natural SA, Jan. S371 Date: Nov. 10, 1998 1996. S 102(e) Date: Nov. 10, 1998 87 PCT Pub. No.: WO97/42963 Primary Examiner Thurman K. Page Assistant Examiner Alysia Berman PCT Pub. Date: Nov. 20, 1997 Attorney, Agent, or Firm Abelman, Frayne & Schwab 30 Foreign Application Priority Data 57 ABSTRACT May 10, 1996 GA Gabon ...... OO2274 This invention refers to the Sphere of medicine, in particular 51 Int. Cl...... A61K 35/78; A61K 9/06 to pharmaceutics and concerns the preparations for burn 52 U.S. Cl...... 424/195.1; 424/443; 424/DIG. 13; treatment. The technical result of the present invention is in 514/886; 514/969 widening the assortment of medicinal preparations for treat 58 Field of Search ...... 424/195.1, 443, ment of bums and wounds, in increasing treatment effect. 424/DIG. 13; 514/969, 886 The ointment contains the components in the following 56) References Cited relation of mass parts: U.S. PATENT DOCUMENTS celandine Chelidonium maius 15-25 g 4,459,285 7/1984 Grollier et al...... 424/74 plantain Plantago major 15-25 g 5,061,491 10/1991 Deryabin ...... 424/195.1 matricary Matricaria channonilla 15-25 g yarrow Achillea millefolium 15-25 g FOREIGN PATENT DOCUMENTS calendula Calendula officinalis 15-25 g St. John's-wort Hypericum perforatum 15-25 g 671336 A5 8/1989 Switzerland. gum-tree Eucalyptus globulus 15-25 g olive oil Oleum olivarun 1000 g OTHER PUBLICATIONS yellow wax of honey Cera flava 80-130 g Database Derwent Publications, No. 97-049981, Leontev et al. Balsam composition with wound-healing properties comprising camphor, essential oil concentrate containing oil 2 Claims, No Drawings 5,997,876 1 2 BURN AND WOUND ONTMENT Calendula's effect grows in combination with matricary and yarrow, Skin epitalization and granulation, local protective This application is a 371 of PCT/GE97/00001 filed May mechanisms increase. 8, 1997. Olive oil-has deeper effect than the vaseline, the skin This invention refers to the sphere of medicine, in absorbs it easily. particular to pharmaceutics and concerns the preparations Honey wax-contains large quantity of VitaminA, which for bum treatment. is necessary, for recovery of skin entirety and provides for There is known calendula ointment Unguentum fast healing of the burn. “Calendula', which contains tincture of calendula (on 70% spirit 1:10)-20 g, vaseline-90 g.: Mashkovskij M. V. Besides, the increase of the quantify of celandine, “Medicinal Means”, Moscow, “Medicine” 1986, vol. 2, p. plantain, matricary, calendula. yarrow, St.John's-wort, gum 2.424). tree in green ointment more than 25 g, of the olive oil more At using this ointment on wound and burn the process of than 1000 g and of the honey yellow wax more than 130 g healing is slowed down, as the ointment contains only one doesn’t promote the treatment efficiency and results in medicinal preparation and Vaseline. Vaseline makes crust on over-expenditure of the raw. the injured Surface, under which the microbes are easily 15 At the same time the reduction of the quantity of reproduced. celandine, plantain, matricary, calendula, yarrow, St.John's- wort, gum-tree below 15 g, of the olive oil below 1000 g and There is also known “Ointment Kolkhuri’, which con of the honey yellow wax below 80 g increases the time of tains St.John's-wort. the oak bark, haw-thom, yarrow, yel treatment and reduces its efficiency. low melilot, horse-chestnut 0.06-0.065 in equal quanity, Method for preparing of green ointment is carried out in nettle 0.10-0.11, gum-tree extract 0.02, belladonna extract the following way: 0.02, vaseline-the rest; GE 13, Darsania, V. 15.05.94). This ointment is used as analgetic and antiinflammatory Small grinded grass-15-25 g of celandine, 15-25 g of means and is less effective for healing the wounds and burns, plantain, 15-25g of matricary, 15-25g of calendula, 15-25 as haw-thorn and belladonna arc not characterized by anti g of yarrow, 15-25g of St.John's-wort, 15-25g of gum-tree inflammatory and regeneration Stimulating effect. The yel 25 is filled in enamel vessel, 1000 g of olive oil is poured in and low melilot and horse-chestnut contain Substances which boiled on water bath during 6 hours, cooled to room tem hinder the blood coagulation and do not effect the skin perature and pressed out. regeneration. The oak bark and nettle have antiinflammatory The obtained oil mass of 700-900 g is boiled again on properties, but it must be mentioned, that tannin involved in water bath and mixed with small cut honey wax Of 80-130 oak bark in reaction with the injured Surface mucous mem g. boiled for 30 minutes, put away and Stirred until cooling brane proteins at burn makes a coat, under which purulent to room temperature. proceSS occurs. The nettle increases the quantity of eryth EXAMPLE 1. rocytes and hemoglobin, which is raised at burn in result of intensified loSS of plasma. Small grinded dried grass-15 g of calendine, 15 g of The technical result of the present invention is in wid 35 plantain, 15 g of matricary, 15 g of calendula, 15 g of yarrow, ening the assortment of medicinal preparations for treatment 15 g of St.John's wort, 15 g of gum-tree is filled in enamel of burns and wounds, in increasing treatment effect. vessel, 1000 g of olive oil is poured in and boiled on water The technical result is achieved by that the green bath during 6 hours, cooled to room temperature and pressed ointment, which contains St.John's-wort, yarrow, gum-tree, out. The obtained oil mass of 900 g is boiled again on water additionally contains celandine, plantain, matricary, 40 bath and mixed with small cut 105 g honey wax, boiled for calendula, olive oil and yellow wax of honey in the follow 30 minutes, put away and Stirred until cooling to room ing relation of components in mass parts: temperature. EXAMPLE 2 celandine Chelidonium maius 15-25 g 45 plantain Plantago major 15-25 g Small grinded dried grass-20 g of calendine, 20 g of matricary Matricaria channonilla 15-25 g plantain, 20g of matricary, 20g of calendula, 20g of yarrow, yarrow Achillea millefolium 15-25 g 20g of St.John's wort, 20g of gum-tree is filled in enamel calendula Calendula officinalis 15-25 g St. John's-wort Hypericum perforatum 15-25 g vessel, 1000 g of olive oil is poured in and boiled on water gum-tree Eucalyptus globulus 15-25 g 50 bath during 6 hours, cooled to room temperature and pressed olive oil Oleum olivarun 1000 g out. The obtained oil mass of 800 g is boiled again on water yellow wax of honey Cera flava 80-130 g bath and mixed with small cut 105 g honey wax, boiled for 30 minutes, put away and Stirred until cooling to room The additional application of celandine, plantain, temperature. matricary, calendula, olive oil and yellow wax of honey in 55 EXAMPLE 3 the ointment in the Said relation of components in mass parts enables to increase treatment effect, which is provided by the Small grinded dried grass-25 g of calendine, 25 g of properties of the grass. plantain, 25g of matricary, 25g of calendula, 25g of yarrow, Celaludine-is characterized by antiinflammatory, local 25g of St.John's-wort, 25g of gum-tree is filled in enamel analgetic, regeneration accelerating effect. 60 vessel, 1000 g of olive oil is poured in and boiled on water Plantain-is characterized by antimicrobic, hemostasia bath during 6 hours, cooled to room temperature and pressed and wound healing effect. out. The obtained oil mass of 700 g is boiled again on water Matricary-is characterized by antiseptic, local analgetic bath and mixed with small cut 130 g honey wax, boiled for and antiinflammatory effect, accelerates regeneration. 30 minutes, put away and Stirred until cooling to room Calendula-strengthens the circulatory vessels walls, 65 temperature. reduces their permeability, what is very important at burn, According to Said examples the ointment was applied on when the capillary conduction and plasinorrhea is increased. the members of the inventor's family and volunteers at 5,997,876 3 4 treatment of I, II, III degree burns, of lacerated, contused, dose, which is equal to 27456.0 mg/kg. The ointment is not incised wounds. At applying the bandage, with patients there characterized by allergic or local-irritation action. was marked-arrest of bleeding, reduction of pain, Stoppage The results of the investigations enable to consider green of purulent discharge, acceleration of granulation and epi ointment as harmless and Safe for human health. thelization. There were not cases of treatment complication, By bacteriological investigations it was Stated that green Such as Suppuration, bleeding, occurrence of the thick coat ointment has bactericidal effect with the microbes of the on the Surface, prolongation of wound healing. The ointment following groups: StaphylococcuS epidermidis, Streptococ effect was marked at the burn of III degree, when all the cus fecalis, Psevdomonas aeruginosa, Escherichia coli. Sources for epithelium reproduction in the injured area For the experiment was made the model of III degree burn needed for skin regeneration are destroyed. on rabbits. The experimental group was treated with green 1. Patient E.D.-woman, 36 years old, resident of Tbilisi, ointment, the control group with 5% liniment of synthomy Marianishvili str. 46. cin. Diagnosis: burn of III degree. By means of electric-paramagnetic resonance were exam There was burned more than 50% of body surface, after ined the Skin, liver, Spleen, glands above kidneys and blood treatment in the hospital during 3 months flection Surface of 15 of experimental and control animals. In result of green the right hand from armpit to hand and chest was left ointment's effect the intensity of ribonucleotide-reductase, unhealed. The only way for healing the wound was skin which indicates the growth of proliferation processes in transplantation, which the patient categorically refused and spleen, was increased by 90% in comparison with control decided to begin treatment with green ointment. Objectively data. We can Say that green ointment is an inductor of the muscle layer was injured on different depth, there was ribonucleotide-reductase. marked bleeding, Violent pain, Swelling of the tissues Under the action of green ointment the intensity of around. In Several minutes after applying the ointment the nonhemic iron nitrizil complexes signal g=2.03, which tes patient felt easing of tension, pain, arrest of bleeding. The tifies the reduction of after burn hypoxia degree in liver as ointment was applied every day during a month, gradually well of methemoglobin and intensity of signals of Mn" in the injured area Skin tubercles occurred, the granulation 25 containing complexes, that is the indicative of hemolysis tissue grew intensively without Suppuration and coating. intensity and preservation of membrane Structure enterity. It The wound was healed in a month without Scars. can be said that green ointment is characterized with mem 2. Patient Sh.N.-woman, 44 years old, resident of brane protective properties, which is determined by the Tbilisi. reduction of lipides peroxide oxidation intensity. The indica tive of membrane stabilizing effect is the reduction of Diagnosis: burn of II degree. The hand was injured, was oxidized ccruloplasmin signal and increase of Fe" trans marked violent redness with different quantity of vesicles ferrin Signal intensity in comparison with control data. with Serous exudates. The ointment was applied 2 times a According to the results of the investigations carried out day during 10 days. The injury healed without Suppuration. by means of electric-paramagnetic resonance method, green 3. Patient T.B. child, 3 years old, resident of Tbilisi. 35 ointment reduces the intensity of lipides peroxide oxidation Diagnosis: lacerated wound. in cells, promotes for preservation of the enterity of mem The child's hand was lacerated with obtuse subject, the brane Structure, reduces hypoxia degree in liver, effects wound was not Sutured, in three days after applying the proliferation processes and is an inductor of ribonucleotide ointment the wound was filled without Scars. 40 reductase. 4. Patient Z.N.-woman, 71 years old. resident of Tbilisi. The results of investigations show that under the effect of Diagnosis: burn of II degree. green ointment with experimental rabbits the primary-coat is With the patient there was marked redness of lower removed earlier, than with the control animals, in result the extremities, vesicles of different sizes filled with liquid. The healing process accelerated. The remove of the coat and ointment was applied every day during 3 weeks. The injury 45 healing acceleration makes 42.31% in comparison with 5% liniment of Synthomycin. At the same time under the effect healed without Scars. of green ointment the inflammatory processes in circulatory 5. Patient I.I.-man, 57 years old, resident of Tbilisi. vessels is leSS expressed, microcirculation is not disrupted, Diagnosis: lacerated wound. thrombosis and Stasis are not marked in the tissues around The patients hand was lacerated deeply with an obtuse 50 the wound. The widened capillaries refer to plasma Subject. The wound was not Sutured. the ointment was capillaries, and that's why around the wound insignificant applied every day during one week. The wound healed cell infiltration of blood elements is marked. These cell without Scars. elements refer to the cells of tissue origin. The pre-clinical investigations of the new medicinal The comparison of healing rate and control rabbits shows, means green ointment were carried out in the Institute for 55 that healing acceleration in experimental animals is pro Experimental and Clinical Medicine of Tbilisi State Uni moted by Sharp activation of cell-tissue elements, increase of versity by GLP Program “The rules of Pre-Clinical Estima phagocytosis, increase of antioxidant activity of blood and tion of Pharmacological Means”, RD 64-126-91, Moscow tissues. The increase of phagocytosis and antioxidant activ 1992. ity of tissues causes the limitation of Secondary alteration, The mechanism of action of the green ointment on the 60 the degradation of inflammatory process modulators and body was Studied by toxicological, microbiological, mediators activity, death of microorganisms. morphological, immunological, pathophysiological, It must be mentioned, that under the effect of green histostructural, biochemical methods. ointment the proliferation processes of connective tissues Green ointment is non-toxic. Its LDso is more than and epithelium elements are carried out Simultaneously. 320-fold therapeutic dose, which is equal to 9152.0 mg/kg. 65 Under the effect of green ointment the immune cell circle green ointment is not characterized by cumulative proper is activated, the quantity of T lymphocytes is increased, the ties. Cumulation LDs is more than 960-fold therapeutic phagocytosis process is accelerated. 5,997,876 S 6 The application of present ointment enables: At applying of green ointment there was no case of widening of the assortment of medicinal preparations for prolongation and complication of the disease. burns and wounds, On the basis of conducted investigations the green oint increase of the treatment efficiency approximately for ment is recommended by Pharmacological Committee as an 42%. effective medicinal means Stimulating regeneration. The clinical approbation of green ointment was carried We claim: out in 6 clinics on 449 patients with different diagnosis. 1. An ointment for the treatment of burns and wounds in Among them, with infected and uninfected wounds -158 patients, with bum disease-75, with purulent damages of mammals, which comprises: hypodermic tissues (carbuncle, furuncle, panaritium, abscess, phlegmon)-26, with trophic ulcers of different Chelidonium maius 15-25 g; etiology-60, with cervical erosion and colpitis-130 Plantago major 15-25 g; patients. Matricaria channonilla 15-25 g; Achillea millefolium 15-25 g; The efficiency of green ointment action was evaluated by Calendula officinalis 15-25 g; following criteria: general condition of a patient, Visual 15 Hypericum perforatum 15-25 g; evaluation of regeneration changes, epitalization terms of Eucalyptus globulus 15-25 g; wound, ulcer and erosion Surfaces, bacteriologic, cytological Oleum olivarun 1000 g; and and colposcopy examinations. Cera flava 80-130 g. The held examinations showed, that the application of green ointment at treatment of mentioned diseases causes 2. A method for the treatment of burns and wounds in the Stimulation of regeneration processes, fast healing, the mammals, which comprises: wounds are healed earlier than classic terms. At treatment period there was observed the fast decrease applying to the Site of a burn or a wound a burn-healing of the purulent discharge, ache and edema of tissues around 25 or a wound-healing effective amount of an ointment the wound, Significant acceleration of wound clearing, compr1SIng improvement of microcirculation, the acceleration of periph eral epitalization processes. Chelidonium majus 15-25 g; At burn disease of I, II and III degrees with the patients Plantago major 15-25 g; there was observed the decrease and elimination of ache and Matricaria chamomilla 15-25 g; plasmorrhea. The treatment results in complete epitalization without Scars. Achillea millefolium 15-25 g; At treatment of acute colpitis the efficiency of ointment Calendula officinalis 15-25 g; action was stipulated by its bactericidal action. After treat Hypericum perforatum 15–25 g; ment in neither cases there was observed the increase of Eucalyptus globulus 15-25 g; pathological microbes, the complete recovery of a patient 35 takes place. Oleum Olivarum 1000 g and At cervical erosion the acceleration of epitalization Cera flava 80-130 g. processes, the recovery of mucous membrane takes place more faster than at treatment with other preparations.

UNITED STATES PATENT AND TRADEMARK OFFICE CERTIFICATE OF CORRECTION PATENT NO. : 5,997,876 DATED : December 7, 1999 INVENTOR(S) : SHIKHASHVIII ET AL. It is certified that error appears in the above-identified patent and that said Letters Patent is hereby Corrected as shown below:

On the Title Page 76) Delete "Ga." both occurrences, insert -- GE.-- Delete "38012", insert -- 380012 --. (30). Foreign Application Priority Data Delete "GA", insert - (GE.) --. In the Specification Column 3, lines 8 and 13 and Column 4, line 9, delete "III", insert --III--, In the Claims Column 5, line 9, delete "burn", insert "burn--. Signed and Sealed this Tenth Day of April, 2001 Zaaé, f-34.

NCHOLAS P. GODC Attesting Officer Acting Director of the United States Patent and Trademark Office