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WO2019098960A2 - Topical pomade developed for warts (papilloms) and orfs appearing as a result of virus infections in animal skin and mucosa - Google Patents

Topical pomade developed for warts (papilloms) and orfs appearing as a result of virus infections in animal skin and mucosa Download PDF

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Publication number
WO2019098960A2
WO2019098960A2 PCT/TR2018/050387 TR2018050387W WO2019098960A2 WO 2019098960 A2 WO2019098960 A2 WO 2019098960A2 TR 2018050387 W TR2018050387 W TR 2018050387W WO 2019098960 A2 WO2019098960 A2 WO 2019098960A2
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WO
WIPO (PCT)
Prior art keywords
skin
pomade
molt
coluber
warts
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Application number
PCT/TR2018/050387
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French (fr)
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WO2019098960A3 (en
Inventor
Mehmet KALE
Ramazan SENCAN
Ahmet Ak
Nuri MAMAK
Sibel YAVRU
Sibel HASIRCIOGLU
Yakup YILDIRIM
Mesih KOCAMUFTUOGLU
Hasbi Sait SALTIK
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Kale Mehmet
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Publication of WO2019098960A2 publication Critical patent/WO2019098960A2/en
Publication of WO2019098960A3 publication Critical patent/WO2019098960A3/en

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
    • A61K35/56—Materials from animals other than mammals
    • A61K35/58—Reptiles
    • A61K35/583—Snakes; Lizards, e.g. chameleons
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/0014—Skin, i.e. galenical aspects of topical compositions

Definitions

  • the invention is related with a pomade curing symptoms of keratitis, hyperkeratosis, warts (papillom), orfs (crust on the wound), nodules, pustules, exanthema, swelling and inflammation developing due to viruses in animal skin and 9a mucosa.
  • Viral skin and mucosal diseases in cattle may be listed as lumpy skin disease (capripoxvirus), cowpox (orthopoxvirus), pseudocowpox (para poxvirus), bovine ulcerative mamillitis (bovine herpesvirus type 2), bovine papillomatosis (bovine papillomavirus), foot-and-mouth disease (picornavirus), bluetongue disease (reovirus), cattle plague (paramyxovirus) and vesicular stomatitis (rhabdovirus).
  • Viral skin and mucosal diseases in sheep and goats may be listed as ecthyma (para poxvirus), border disease (pestivirus), bluetongue disease (reovirus), peste desdriven ruminants (paramyxovirus), sheep pox (capripoxvirus), goat pox (capripoxvirus) and foot-and-mouth disease (picornavirus).
  • Viral skin and mucosal diseases in cats and dogs may be seen as canine oral papillomatozis (canine papillomavirus), feline immunodeficiency virus, distemper (canine distemper) and lymphosarcomata, canine ttl herpesvirus and hepatitis contagiosa canis in dogs.
  • This invention has been tested in consideration of scientific applications on skin and mucosal lesions caused by bovine papilloma virus in cattle, skin and 3 ⁇ 4 mucosal lesions caused by parapoxvirus in goats and skin and mucosal lesions caused by canine papillomavirus in dogs. The results have been proved to be highly satisfying.
  • Bovine papillomatosis infection is occured by bovine papilloma virus.
  • This virus causes benign tumoral formations to appear on skin and cutaneous areas of 3 ⁇ 4 ⁇ cattle. It appears in eyes, heads, teats and other areas of skin as epithelium hyperplasia and connective tissue proliferations. These tumors are in the appearance of ricegrain and sharp nails and they might hinder vital functions in both internal and external organs of animals in consequence of their growth (cauliflower, walnut size). This condition may cause weight loss and low milk yield. 13 subtypes of bovine 3 ⁇ 4 papilloma virus have been detected so far.
  • bovine papillomatosis infection such as fungiform skin papillomatosis, filiform skin papillomatosis, mucosal papillomatosis and visceral papillomatosis.
  • Papillomas occur locally and singly.
  • bovine papilloma virus is transmitted by contact, mosquitoes and subcutaneous injection might cause fibroblast proliferation developed between stratum spinosum and stratum corneum in skin.
  • the developed primary nodules grow and are keratinized. Warts appearing as a result of bovine papilloma virus are mostly seen on heads, necks, shoulders, eyes, abdomen and teat skin areas.
  • the importance of bovine papilloma virus in terms of teat health in cattle may be regarded as following:
  • ttl 3-Mastitis might be seen as a result of warts on teats.
  • 4-Bacteria access from the wounded area is possible due to the fact that warts come off as such or following a trauma.
  • cauterization for treatment of bovine papilloma virus in cattle, cauterization, autohemotherapy, surgical operations, autologous vaccines, ligature fixation, cryotherapy and some chemical magistral drug applications are commonly used.
  • ecthyma contagious pustular dermatitis, orf, crusty mouth, contagious pustular dermatitis.
  • This disease has a zoonotic characteristic for humans.
  • E cthyma disease in goats is widely seen both in our country and worldwide. The disease proceeds commonly and severely in lambs. It may slightly be seen in adults. The disease is mostly seen during lambing seasons. 3 ⁇ 4 ⁇ Contact with infected animals and contaminated materials (needles, syringes, clippers, surgical tools etc.) is the most crucial way for the disease to transmit.
  • E cthyma disease may be seen especially as a result of traumas impairing the integrity of skin on lips, buccal cavity, gingiva, foot coronary band and 3 ⁇ 4 teats.
  • the first replication of the virus causing the disease is seen on the spot where it enters the body.
  • E rythema, papule, pustule and crustation phases are seen.
  • C linical forms of ecthyma are grouped as labial, podal, genital and malignant. Goat kids are the most influenced ones by the disease.
  • E specially muco-cutaneous layer of the mouth is influenced by the viral agent. These animals usually die as they cannot suck their mothers. Under this condition, economical loss is surplus.
  • vaccination, antibiotical applications for secondary bacterial infections, immune supportive drugs and glycerin iodUe treatment is recommended.
  • Canine oral papillomatozis is usually formed by canine papillomaviruses as multiple in all dogs and sporadically in young dogs. According to estimations, there are at least 5 types of virus.
  • Papillomas are generally seen on lips, cheeks, tongue, palate, gingiva and pharynx. They also exist on inner ear, skin, penis and vagina. Warts are able to turn into keratinized cells from epithelial character. Warts occurring on skin and mucosal tissues can vary in growth from the size of a chickpea ttl up to the size of a cauliflower.
  • S ince epithelium cells are infected by the virus, hyperplasia, degeneration and hyperkeratinisation might appear in stratum spinosum cells.
  • multiple tumors (100 and over) might be seen in lips, tongue, palate, epiglottis, upper esophagus and oropharynx mucosa. Ulceration and bleeding may appear as a result of the traumas from the teeth. Bad breath and fluxion may be seen in the mouth. S hortness of breath is possible as a result of the pressure on the respiratory tract.
  • Palpebra, cornea and conjunctiva papillomas might also be seen as a result of canine oral papillomatozis.
  • Cowpox characterized by vesiculous-papullose exanthems that might be seen in teats, testicles and other hairless parts of the body, is a viral infection.
  • the disease is occured by vaccinia virus from poxvirus family or the original cowpoxvirus.
  • the agent is transmitted by direct contact from the skin, respiratory or digestive tract 3 ⁇ 4 3 ⁇ 4 mucosas.
  • Teatpox (pseudocowpox) from paravaccinia group is an infection characterized by pox-like formations on teats of parapoxvirus bovis 2. Teat epithelium injuries ease the existence of the disease. Milking machines or manual milking play an important role in the indirect transmission of the disease. It is a zoonotic disease. E rythema, papule and crustation phases are seen in skin and mucosa. There is no treatment.
  • Bovine papular stomatitis from paravaccinia group is an infection characterized by papullose exanthema formations on teat, palate mucosa, tongue, lips, esophagus and cutaneous mucosas of the rumen of parapoxvirus bovis 1.
  • the transmission takes place by contact and infected food. It is a zoonotic disease. No application is performed since the disease does not have a great economical importance.
  • ttl Lumpy skin disease (nodular exanthema of cattle) is a viral infection that is typically seen in the skin and is characterized by nodules and lumps and requires obligatory report. Low milk yield, mastitis and skin damage is regarded important in terms of the disease.
  • the virus is transmitted by flies, nasal and eye flow, semen, saliva, milk, dirty water and food, crusty wounds and uncontrolled animal movements. Nodules all over the body, oedema and wounds on teat area, chest and legs, typical nodular lesions on head and supraorbital skin are seen.
  • the disease requires vaccination, combat with flies, quarantine, cleaning, disinfection and controlling animal movements.
  • Bovine mamillitis from alphaherpesvirus subgroup of herpesvirus group is an infection characterized by ulcerative changes on teats, mouth, vulva and vagina mucosas of bovine herpesvirus 2.
  • Mechanical vectors, mechanical milking, subclinical infected animals, environmental conditions, sensitivity and stress factors are important in transmission of the disease. As the virus is latent, vaccination is 3 ⁇ 4 ⁇ limited.
  • the invention is about a pomade prepared with 3 different formulations for viral keratitis, hyperkeratozis, warts (papilloma), orfs, nodules, pustules, blisters, lumps and rashes seen on animal skin and mucosa.
  • the first formulation is composed of 150 portion of lanolin, 8 portion of Coluber jugularis jugularis molt and 42 portion of alcohol.
  • the second formulation is composed of 75 portion of lanolin, 75 portion of vaseline, 8 portion of C oluber caspius molt 21 portion of alcohol and 21 portion of ether.
  • the third formulation is composed of 70 portion of lanolin, 70 portion of vaseline, 8 portion of Coluber caspius molt, 27 portion of alcohol, 8 portion of glacial acetic acid, 2 portion of podophyllin and 15 portion of ether. All three pomades may be used all over the animal body on teats, mouths, supraorbital, regio interdigitalis and skin and mucosa of anal and genital areas. It is an odorous pomade ttl with the right thickness of fine powder and is reliable, effective with no side effects and it can be produced and undergo quality control.
  • the first pomade is prepared as following;
  • the pulverized active substance (Coluber jugularis jugularis molt) was taken ttl into a tared glass beaker and its weight was stated in grams on microbalances.
  • the active substance (Coluber jugularis jugularis molt) was poured on lanolin as the amount in the formula. Lanolin and active substance was mixed thoroughly.
  • I 99.8% isopropyl alcohol was added in the mixture of lanolin and active substance as the amount in the formula by the help of a glass pipette and mixed.
  • the formulation was prepared with this methodology.
  • the first formulation was kept in room temperature.
  • the pomade has semi ttl fluidity in room temperature, it is odorous and it has fine powder specialty when applied on the skin. No irritation after a fleeting paresthesias, inflammation and rash was seen following the application on sensitive skin such as teats.
  • C hemical and pharmacological features :
  • the head part of this snake is characteristic and the neck part may be slightly characteristic.
  • the upper part of the head is 3 ⁇ 4 ⁇ covered with bright scales. E ach of these scales carries apical pores.
  • the tip of the rostrum is sharp and rostral plate can easily be seen from the upper side. Out of the two praeoculare, the upper one might be large and divided, and the lower one is quite small. Postocularia is rarely three but usualy two, and subralabialia is rarely seven but mostly eight.
  • Ventralia has 3 ⁇ 4 189-220 scales and subcaudalia has 99-128 scales.
  • the upper part of the body of adults is usually uniform bright black. There are no round black spots on the sides of the neck.
  • the lower part of the body of adults has red spots scattered over black or black spots scattered over red surface.
  • the dorsal part is brown, olive or yellowish grey, and they have dark spots.
  • the ventral surface of the youngsters has blackish spots.
  • the Coluber jugularis jugularis molt used in the study corresponds with epidermis layer of the skin. This layer is found on body surface and is released in nature by molting (relining) periodically.
  • the epidermal layer is composed of Oberh ⁇ tchen (cuticle layer), ⁇ f-layer, mesos layer, -layer, lacunar tissue and clean layers as outside-in.
  • C uticle and ⁇ -layers face outer surface, and they are hard, strong, nonflexible and soft, -layer is the flexible inner layer.
  • ⁇ f keratin distribution is regarded in snake epidermis.
  • the chemical structure of ⁇ -keratin molecule has been proved to be harder and not more elastic compared to -keratin.
  • Lanolin (Lanoline, G raisse de Laine, Adeps lanae-Refined Wool Oil-Lanae cera-Lanoleine): It is obtained from sheep wool. It is light yellow and pasty. It is 3 ⁇ 4 dissolved in ether, petrol ether, chloroform and hot alcohol. It absorbs water twice its weight. It is emulgator. It performs water/oil emulsion. Its consistence is hard without water. When water is added, it becomes pasty. It absorbs water at its weight. It is absorbed easily by skin. It is non-flavored. It is used as excipient.
  • Isopropyl alcohol 99.8%: It is a clear, flammable alcohol with an odour of 3 ⁇ 4 ⁇ ethanol and acetone mixture. It creates a solution at all rates in water, ethanol, acetone, chloroform and benzene. It has a colorless fluid appearance.
  • C3H8O is the chemical formula. It is also known as isopropanol. It is used as a solvent in purification and extraction of natural products. It is also used in purification, crystallization and precipitation of organic chemicals.
  • Lanolin provides a decisive, homogenous and smooth emulsion in the formulation by ensuring a good mixture of alcohol and Coluber jugularis jugularis molt. It also provides the easy absorption of Coluber jugularis jugularis molt by the skin and its permanence.
  • Isopropyl alcohol is used as a solvent in purification and extraction of Coluber jugularis jugularis molt.
  • Bovine papilloma virus antigen presence was found positive in all animals. In wart tissue samples from three ttl of these animals, Bovine papilloma virus genome presence was studied by PC R test.
  • Bovine papilloma virus genome presence was found positive in all animals.
  • Tissue or swap samples taken by swap from 10 goats that were suspected to have ecthyma and used in the study were studied by Real-Time PC R in terms of parapoxvirus presence. Parapoxvirus was found positive in all animals. Blood leukocyte samples from 5 dogs that were suspected to have been infected by canine oral papilloma virus and used in clinical studies were studied by E LISA test in terms of canine oral papillomavirus antigen presence. Canine oral papillomavirus antigen presence was found positive in all dogs. Canine oral 3 ⁇ 4 papillomavirus genome presence in blood leucocyte samples from 3 of these animals was studied by PC R test. Canine oral papillomavirus genome presence was found positive in all animals. Mouth papilloma sample from 1 of these animals was studied by electron microscopy and canine oral papillomavirus presence was monitored.
  • Canine oral papillomatozis clinical symptoms of canine papillomavirus in dogs (warts seen on lips, cheeks, tongue, palate, gingiva etc.) and ecthyma clinical symptoms of parapoxvirus in goats (keratitis, hyperkeratozis, orfs, 3 ⁇ 4 3 ⁇ 4 pustules, blisters, lumps and rashes appearing on areas such as lips, buccal cavity, gingiva and foot coronary band and teats etc.) were treated.
  • Our second pomade formulation with 4% active substance is composed of 75 portion of lanolin, 75 portion of Vaseline, 8 portion of Coluber caspius molt, 21 portion of isopropyl alcohol (99.8%) and 21 portion of ether.
  • Our second pomade formulation was used for keratitis, hyperkeratosis, orfs, nodules, pustules, blisters, lumps and rashes appearing on sensitive areas such as teat and mouth skin and mucosa.
  • the second pomade is prepared as following;
  • the pulverized active substance (Coluber caspius molt) was taken into a tared ti glass beaker and its weight was stated in grams on microbalances.
  • the second formulation mixture was kept in room temperature.
  • the pomade has semi fluidity in room temperature, it is odorous and it has fine powder specialty when applied on the skin. No irritation after a fleeting paresthesias, inflammation and 3 ⁇ 4 ⁇ rash was seen following the application on sensitive skin such as teats.
  • C oluber Hierophis caspius G ME LIN, 1789. It is also named as Hazer snake and G ray Yuruk. It is mostly seen around Balkan countries, S outhern Russia and Caucasia. In our country, it lives in Thracian, Aegean, Mediterranean, Western Black S ea and Central Anatolia regions. This snake has a high biting tendency and is non-poisonous. The head part is large and the neck part is narrow. It may grow up to 180 centimeters. The dorsal scales are flat and rarely slightly keeled. There are two holes at the tip of each scale. The number of scales around the body is 19, but rarely 17.
  • the number of scales on its skin ventral varies between 190-215 and between 90-113 on subcaudal.
  • This snake does not have black spots on sides of its neck.
  • the lower part of its body is yellowish white, spotless and sometimes there are thin black spots beneath the tail.
  • the dorsal part is grey-brown, olive or yellowish grey.
  • the middle part of dorsal scales has a lighter color than the edges. There are no thin white lines on the edges.
  • the upper part of the head is mostly refractory brown, dark spotted or sometimes grey/dark brown.
  • the Coluber caspius molt used in the study corresponds with the epidermis ttl (upper skin) layer of the skin. This layer is located on body surface and is released in nature for molting (relining) periodically.
  • the epidermal layer is composed of Oberh ⁇ tchen (cuticle layer), ⁇ f-layer, mesos layer, -layer, lacunar tissue and clean layers as outside-in.
  • C uticle and ⁇ -layers face outer surface, and they are hard, strong, nonflexible and soft, -layer is the flexible inner layer.
  • ⁇ f keratin distribution is regarded in snake epidermis.
  • the chemical structure of ⁇ -keratin molecule has been proved to be harder and not more elastic compared to -keratin.
  • Lanolin (Lanoline, G raisse de Laine, Adeps lanae-Refined Wool Oil-Lanae cera-Lanoleine): It is obtained from sheep wool. It is light yellow and pasty. It is dissolved in ether, petrol ether, chloroform and hot alcohol. It absorbs water twice its weight. It is emulgator. It performs water/oil emulsion. Its consistence is hard without water. When water is added, it becomes pasty. It absorbs water at its weight. It is 3 ⁇ 4 absorbed easily by skin. It is non-flavored. It is used as excipient.
  • Vaseline (paraffinum album, Vaseline blanch, vaselinum album, petrolatum album): It is an oily excipient providing a moisturizing effect on the skin and used for skin care and treatment of skin irritation. It is obtained from the remainder substance after petrol distillation. It is formed by whitening soft yellow paraffin. It is not dissolved in water but is dissolved in alcohol slightly and easily in ether, chloroform, benzole, essence and oil. It is not absorbed, does not cause irritation and is used as pomade excipient. It is odourless and tasteless.
  • Isopropyl alcohol 99.8%: It is a clear, flammable alcohol with an odour of ethanol and acetone mixture. It creates a solution at all rates in water, ethanol, acetone, chloroform and benzene. It has a colorless fluid appearance.
  • C3H8O is the chemical formula. It is also known as isopropanol. It is used as a solvent in purification and extraction of natural products. It is also used in purification, crystallization and precipitation of organic chemicals.
  • Isopropyl alcohol is used as a solvent for purification and extraction of C oluber ttl caspius molt. It functions as a solvent. Alcohol shows its effect by coagulating proteins and melting lipids.
  • Ether (Aether, Ether anesthesicus, Diethyl ether, Ether sulfurique, Ether T.K.): It is diethyl ether supplemented by antioxidants. It is a clear, colorless, volatile, easily flammable, characteristic scented and highly quick fluid. The boiling point is 34-35 eC . It is dissolved in water between 1 :12 and 15. It mixes in alcohol, chloroform, methylene chloride, petrol ether, stable and volatile oils. 93 drops weigh 1 gram. It has a myorelaxant effect.
  • S ince the Coluber caspius molt has various substances and enzymes in its 3 ⁇ 4 epidermal structure, our pomade has great importance for it heals keratitis, hyperkeratozis, pustules, blisters, lumps and rashes created by viruses on skin and mucosal structures and for it hinders the viral replication within the cell or provides death.
  • Lanolin provides a decisive, homogenous and smooth emulsion in the 3 ⁇ 4 ⁇ formulation by ensuring a good mixture of alcohol and Coluber caspius molt. It also provides the easy absorption of Coluber caspius molt by the skin and its permanence.
  • Vaseline is the last supplemented component in the formula. It was used to increase the absorption of active substance at body temperature from the skin and 3 ⁇ 4 mucosal surface. It also has a softener effect.
  • Bovine papillomavirus antigen presence was found positive in all animals.
  • Bovine papillomavirus genome presence was studied by PC R test.
  • BPV genome presence was found positive in all animals.
  • Tissue or swap samples taken by swap from 20 goats that were suspected to have ecthyma and used in the study were studied by Real-Time PC R in terms of parapoxvirus presence. Parapoxvirus was found positive in all animals.
  • our third pomade formulation really hard and large keratitis, hyperkeratosis, warts (papilloma), nodules, pustules, blisters, lumps and rashes appearing on teat, head, neck, dorsal, foot and face etc. skin and mucosa of dairy cattle as a result of papillomavirus were treated.
  • Our third pomade formulation with 4% active substance is composed of 70 portion of lanolin, 70 portion of vaseline, 8 portion of Coluber caspius molt, 27 portion of isopropyl alcohol (99.8%), 8 portion of 3 ⁇ 4 glacial acetic acid, 2 grams of podophyllin (1 %) and 15 portion of ether.
  • the third pomade is prepared as following;
  • the pulverized active substance (Coluber caspius molt) was taken into a tared glass beaker and its weight was stated in grams on microbalances.
  • the third formulation mixture was kept in room temperature.
  • the pomade has semi fluidity in room temperature, it is acidic odorous and it has fine powder speciality ttl when applied on the skin. Irritation was seen after a fleeting paresthesias, inflammation and rash following the application on sensitive skin such as teats. Therefore, we recommend the pomade to be used for really hard and large keratitis, hyperkeratosis and wart (papilloma) formations appearing on teat, head, neck, dorsal, foot and face etc. skin and mucosa. We also recommend it not to be used on teats, face and eyes, and even if it should be used, limited application should be regarded. In case of any irritation, inflammation and rashes, washing the area with water is recommended. In this kind of cases, water wash may be possible in four 3 ⁇ 4 hours after applying the pomade.
  • C oluber Hierophis caspius G ME LIN, 1789. It is also named as Hazer snake and G ray Yuruk. It is mostly seen around Balkan countries, S outhern Russia and Caucasia. In our country, it lives in Thracian, Aegean, Mediterranean, Western Black S ea and Central Anatolia regions. This snake has a high biting tendency and is non-poisonous. The head part is large and 3 ⁇ 4 the neck part is narrow. It may grow up to 180 centimeters. The dorsal scales are flat and rarely slightly keeled. here are two holes at the tip of each scale. The number of scales around the body is 19, but rarely 17.
  • the number of scales on its skin ventral varies between 190-215 and between 90-113 on subcaudal.
  • This snake does not have black spots on sides of its neck.
  • the lower part of its body is yellowish white, spotless and sometimes there are thin black spots beneath the tail.
  • the dorsal part is grey-brown, olive or yellowish grey.
  • the middle part of dorsal scales has a lighter color than the edges. There are no thin white lines on the edges.
  • the upper part of the head is mostly refractory brown, dark spotted or sometimes grey/dark brown.
  • the Coluber caspius molt used in the study corresponds with the epidermis (upper skin) layer of the skin. This layer is located on body surface and is released in nature for molting (relining) periodically.
  • the epidermal layer is composed of Oberh ⁇ tchen (cuticle layer), ⁇ f-layer, mesos layer, -layer, lacunar tissue and clean layers as outside-in.
  • C uticle and ⁇ -layers face outer surface, and they are hard, strong, nonflexible and soft, -layer is the flexible inner layer.
  • ⁇ f keratin ttl distribution is regarded in snake epidermis.
  • the chemical structure of ⁇ -keratin molecule has been proved to be harder and not more elastic compared to -keratin.
  • 3 ⁇ 4 S ince the Coluber caspius molt has various substances and enzymes in its epidermal structure, our pomade has great importance for it heals keratitis, hyperkeratosis, pustules, blisters, lumps and rashes created by viruses on skin and mucosal structures and for it hinders the viral replication within the cell or provides death.
  • Lanolin (Lanoline, G raisse de Laine, Adeps lanae-Refined Wool Oil-Lanae cera-Lanoleine): It is obtained from sheep wool. It is light yellow and pasty. It is dissolved in ether, petrol ether, chloroform and hot alcohol. It absorbs water twice its weight. It is emulgator. It performs water/oil emulsion. Its consistence is hard without water. When water is added, it becomes pasty. It absorbs water at its weight. It is 3 ⁇ 4 absorbed easily by skin. It is non-flavored. It is used as excipient.
  • Lanolin provides a decisive, homogenous and smooth emulsion in the formulation by ensuring a good mixture of alcohol and Coluber caspius molt. It also provides the easy absorption of Coluber caspius molt by the skin and its permanence.
  • Vaseline (paraffinum album, Vaseline blanch, vaselinum album, petrolatum album): It is an oily excipient providing a moisturizing effect on the skin and used for skin care and treatment of skin irritation. It is obtained from the remainder substance after petrol distillation. It is formed by whitening soft yellow paraffin. It is not dissolved in water but is dissolved in alcohol slightly and easily in ether, chloroform, benzole, essence and oil. It is not absorbed, does not cause irritation and is used as pomade excipient. It is odourless and tasteless.
  • Isopropyl alcohol (99.8%): It is a clear, flammable alcohol with an odour of ethanol and acetone mixture. It creates a solution at all rates in water, ethanol, acetone, chloroform and benzene. It has a colorless fluid appearance.
  • C3H8O is the ttl chemical formula. It is also known as isopropanol. It is used as a solvent in purification and extraction of natural products. It is also used in purification, crystallization and precipitation of organic chemicals.
  • Isopropyl alcohol is used as a solvent for purification and extraction of C oluber caspius molt. It functions as a solvent. Alcohol shows its effect by coagulating proteins and melting lipids.
  • Ether (Aether, Ether anesthesicus, Diethyl ether, Ether sulfurique, Ether T.K.):
  • G lacial acetic acid (G lacial acetic acid, ethanoic acid, concentrated acetic acid, 3 ⁇ 4 E ssigsaure-Acetique acide glacial F P): It is an antibacterial and antifungal agent.
  • Glacial acetic acid burns the skin, gives permanent damage to the eyes and causes blisters on the skin. The effects are felt a few hours later.
  • Glacial acetic acid is in the form of semi-transparent crystals or a sharp scented colorless fluid. The boiling point is between 1 17-1 18 eC . It mixes with water, alcohol, methylen chloride and glycerin. pH is between 2.8-3.4.
  • glacial acetic acid was used on the purpose of antibacterial, antifungal, astringent (tissue shrinker) and escharotics (burning, corrosive) applications.
  • Podophyllin (Podofillum, Podofilino, Podophillinum, Podophyllum rhizome, wild mandrake): Podophyllin is a topical cytotoxic agent. For humans, it is used in treatment of genital warts and other papillomas. Podophyllin resin shows an antimitotic effect and is mainly used in treatment of anogenital warts (kondiloma akuminata). In our country, it is used in treatment of veneral and common benign warts, granuloma inguinale and plantar warts. It was approved in 1945 in USA by ttl F DA and on April 3 rd 2008 in T urkey to be used for treatment of human papillomas.
  • podophyllin assists the active substance and shows its effect by fundamentally stopping the mitotic division during metaphase.
  • the basic effect of podophyllin depends on its primary acantholytic characteristic.
  • the tumor undergoes exfoliation as a consequence.
  • Dense morphological changes appear in epithelial cells.
  • Podophyllin stops the mitosis in epithelial cells during metaphase. This substance is effective on warts that store less keratin. It does not create a lytic effect beyond epidermal cell layer. It has minimal effect on corium layer. It does not leave any scars in topical applications.
  • Podophyllin which is applied 3 ⁇ 4 topically has no systematic effect.
  • Bovine papillomavirus antigen presence was found positive in all animals.
  • bovine papillomavirus genome presence was studied by PC R test, bovine papillomavirus genome presence was found positive in all animals.

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  • Medicines Containing Plant Substances (AREA)

Abstract

The invention is about a pomade to cure keratitis, hyperkeratosis, warts (papillomas), orfs, nodules, pustules, blisters, lumps and rashes developing with viruses in animal skin and mucosa.

Description

TOPICAL POMADE DEVE LOP E D FOR WARTS (PAPIL LOMS) AND OR FS AP P E ARING AS A R E S ULT OF VIR US INF E CTIONS IN ANIMAL S KIN AND
MUCOSA
TE C HNICAL FIE L D
The invention is related with a pomade curing symptoms of keratitis, hyperkeratosis, warts (papillom), orfs (crust on the wound), nodules, pustules, exanthema, swelling and inflammation developing due to viruses in animal skin and 9a mucosa.
P RIOR ART
Many symptoms appear in animal skin and mucosa depending on infectious and non-infectious reasons. These symptoms, seen especially on farm animals such ¾ as cattle, sheep and goat, cause economical losses. On our day, treatment of viral skin and mucosal diseases is both difficult and product range (antiviral cream / pomade) is highly limited. Farm animals and dogs also have zoonotic characteristics of viral skin and mucosal diseases. This condition is crucial in terms of public health.
Viral skin and mucosal diseases in cattle may be listed as lumpy skin disease (capripoxvirus), cowpox (orthopoxvirus), pseudocowpox (para poxvirus), bovine ulcerative mamillitis (bovine herpesvirus type 2), bovine papillomatosis (bovine papillomavirus), foot-and-mouth disease (picornavirus), bluetongue disease (reovirus), cattle plague (paramyxovirus) and vesicular stomatitis (rhabdovirus). Viral skin and mucosal diseases in sheep and goats may be listed as ecthyma (para poxvirus), border disease (pestivirus), bluetongue disease (reovirus), peste des petits ruminants (paramyxovirus), sheep pox (capripoxvirus), goat pox (capripoxvirus) and foot-and-mouth disease (picornavirus). Viral skin and mucosal diseases in cats and dogs may be seen as canine oral papillomatozis (canine papillomavirus), feline immunodeficiency virus, distemper (canine distemper) and lymphosarcomata, canine ttl herpesvirus and hepatitis contagiosa canis in dogs.
Lesions appearing as a result of virus infections in teats and mouths of cattle, sheep and goats might cause fundamental problems causing economical losses such as mastitis, occlusion of teats, no manual or machine milking, no sucking by newborn, extension of lesions within the herd, low quality of skin and meat and low milk yield. Therefore, losses can be minimized by the newly developed invention.
This invention has been tested in consideration of scientific applications on skin and mucosal lesions caused by bovine papilloma virus in cattle, skin and ¾ mucosal lesions caused by parapoxvirus in goats and skin and mucosal lesions caused by canine papillomavirus in dogs. The results have been proved to be highly satisfying.
Bovine papillomatosis infection is occured by bovine papilloma virus. This virus causes benign tumoral formations to appear on skin and cutaneous areas of ¾Ί cattle. It appears in eyes, heads, teats and other areas of skin as epithelium hyperplasia and connective tissue proliferations. These tumors are in the appearance of ricegrain and sharp nails and they might hinder vital functions in both internal and external organs of animals in consequence of their growth (cauliflower, walnut size). This condition may cause weight loss and low milk yield. 13 subtypes of bovine ¾ papilloma virus have been detected so far. Four clinical forms appear in bovine papillomatosis infection, such as fungiform skin papillomatosis, filiform skin papillomatosis, mucosal papillomatosis and visceral papillomatosis. Papillomas occur locally and singly. The fact that bovine papilloma virus is transmitted by contact, mosquitoes and subcutaneous injection might cause fibroblast proliferation developed between stratum spinosum and stratum corneum in skin. The developed primary nodules grow and are keratinized. Warts appearing as a result of bovine papilloma virus are mostly seen on heads, necks, shoulders, eyes, abdomen and teat skin areas. The importance of bovine papilloma virus in terms of teat health in cattle may be regarded as following:
1 -They prevent milking clusters from holding onto teats and cause airflow into the system. No milking can be performed when they are common.
2-They cause pain during milking. Hence, milk drop into teats is decreased and milk yield is low. When milking clusters are mounted, some cows start kicking because of pain.
ttl 3-Mastitis might be seen as a result of warts on teats.
4-Bacteria access from the wounded area is possible due to the fact that warts come off as such or following a trauma. For treatment of bovine papilloma virus in cattle, cauterization, autohemotherapy, surgical operations, autologous vaccines, ligature fixation, cryotherapy and some chemical magistral drug applications are commonly used.
The disease characterized by para poxviruses in goats and pustular and crusty ¾ lesions on lips and nose tips is called ecthyma (contagious pustular dermatitis, orf, crusty mouth, contagious pustular dermatitis). This disease has a zoonotic characteristic for humans. E cthyma disease in goats is widely seen both in our country and worldwide. The disease proceeds commonly and severely in lambs. It may slightly be seen in adults. The disease is mostly seen during lambing seasons. ¾Ί Contact with infected animals and contaminated materials (needles, syringes, clippers, surgical tools etc.) is the most crucial way for the disease to transmit. Forage change and tramping around pastures with thistle, blackthorn and stubble is also important. E cthyma disease may be seen especially as a result of traumas impairing the integrity of skin on lips, buccal cavity, gingiva, foot coronary band and ¾ teats. The first replication of the virus causing the disease is seen on the spot where it enters the body. E rythema, papule, pustule and crustation phases are seen. C linical forms of ecthyma are grouped as labial, podal, genital and malignant. Goat kids are the most influenced ones by the disease. E specially muco-cutaneous layer of the mouth is influenced by the viral agent. These animals usually die as they cannot suck their mothers. Under this condition, economical loss is surplus. Hence, within the herds where the disease is seen, vaccination, antibiotical applications for secondary bacterial infections, immune supportive drugs and glycerin iodUe treatment is recommended.
Canine oral papillomatozis is usually formed by canine papillomaviruses as multiple in all dogs and sporadically in young dogs. According to estimations, there are at least 5 types of virus. Papillomas (warts) are generally seen on lips, cheeks, tongue, palate, gingiva and pharynx. They also exist on inner ear, skin, penis and vagina. Warts are able to turn into keratinized cells from epithelial character. Warts occurring on skin and mucosal tissues can vary in growth from the size of a chickpea ttl up to the size of a cauliflower. S ince epithelium cells are infected by the virus, hyperplasia, degeneration and hyperkeratinisation might appear in stratum spinosum cells. Within the mucocutaneous intersection around the mouth in canine oral papillomatozis, multiple tumors (100 and over) might be seen in lips, tongue, palate, epiglottis, upper esophagus and oropharynx mucosa. Ulceration and bleeding may appear as a result of the traumas from the teeth. Bad breath and fluxion may be seen in the mouth. S hortness of breath is possible as a result of the pressure on the respiratory tract. Palpebra, cornea and conjunctiva papillomas might also be seen as a result of canine oral papillomatozis. All dogs are sensitive to the disease as direct ¾ and indirect contact is crucial for the infection. Autologous vaccination treatment applications are highly important. S upportive treatment applications (corticosteroids) may also be performed. Large warts that are formed in advanced level and that might influence vital functions may be removed by surgical operations (excision, cryosurgery, electrosurgery). However, this should not be regarded as a definitive ¾Ί treatment method. There is no drug therapy.
Cowpox, characterized by vesiculous-papullose exanthems that might be seen in teats, testicles and other hairless parts of the body, is a viral infection. The disease is occured by vaccinia virus from poxvirus family or the original cowpoxvirus. The agent is transmitted by direct contact from the skin, respiratory or digestive tract ¾¾ mucosas. E rythemas, papule oedemas (stadium papillosum), pox centers (stadium pustulosum) and lesions run dry (stadium crustosum) and get crusty in the area where they appear. There is no treatment.
Teatpox (pseudocowpox) from paravaccinia group is an infection characterized by pox-like formations on teats of parapoxvirus bovis 2. Teat epithelium injuries ease the existence of the disease. Milking machines or manual milking play an important role in the indirect transmission of the disease. It is a zoonotic disease. E rythema, papule and crustation phases are seen in skin and mucosa. There is no treatment.
Bovine papular stomatitis from paravaccinia group is an infection characterized by papullose exanthema formations on teat, palate mucosa, tongue, lips, esophagus and cutaneous mucosas of the rumen of parapoxvirus bovis 1. The transmission takes place by contact and infected food. It is a zoonotic disease. No application is performed since the disease does not have a great economical importance.
ttl Lumpy skin disease (nodular exanthema of cattle) is a viral infection that is typically seen in the skin and is characterized by nodules and lumps and requires obligatory report. Low milk yield, mastitis and skin damage is regarded important in terms of the disease. The virus is transmitted by flies, nasal and eye flow, semen, saliva, milk, dirty water and food, crusty wounds and uncontrolled animal movements. Nodules all over the body, oedema and wounds on teat area, chest and legs, typical nodular lesions on head and supraorbital skin are seen. The disease requires vaccination, combat with flies, quarantine, cleaning, disinfection and controlling animal movements.
¾ Bovine mamillitis from alphaherpesvirus subgroup of herpesvirus group is an infection characterized by ulcerative changes on teats, mouth, vulva and vagina mucosas of bovine herpesvirus 2. Mechanical vectors, mechanical milking, subclinical infected animals, environmental conditions, sensitivity and stress factors are important in transmission of the disease. As the virus is latent, vaccination is ¾Ί limited.
There are no specific antiviral drugs to treat viral diseases in animal skin and mucosa. Corticosteroids, local anesthetics and antibiotics are commonly used. Viral lesions on teats, skin and mucosa are transmitted by milking, calf sucking, direct and indirect factors, recovery is delayed because of secondary bacterial factors, mastitis ¾ appears on teats and many animals are slaughtered. Therefore, developing alternative treatment methods is significant.
B RIE F DE S C RIPTION OF THE INVE NTION
The invention is about a pomade prepared with 3 different formulations for viral keratitis, hyperkeratozis, warts (papilloma), orfs, nodules, pustules, blisters, lumps and rashes seen on animal skin and mucosa. The first formulation is composed of 150 portion of lanolin, 8 portion of Coluber jugularis jugularis molt and 42 portion of alcohol. The second formulation is composed of 75 portion of lanolin, 75 portion of vaseline, 8 portion of C oluber caspius molt 21 portion of alcohol and 21 portion of ether. The third formulation is composed of 70 portion of lanolin, 70 portion of vaseline, 8 portion of Coluber caspius molt, 27 portion of alcohol, 8 portion of glacial acetic acid, 2 portion of podophyllin and 15 portion of ether. All three pomades may be used all over the animal body on teats, mouths, supraorbital, regio interdigitalis and skin and mucosa of anal and genital areas. It is an odorous pomade ttl with the right thickness of fine powder and is reliable, effective with no side effects and it can be produced and undergo quality control. DE TAIL E D DE S C RIPTION OF THE INVE NTION
Our first pomade formulation with 4% active substance was used for the treatment of keratitis, hyperkeratozis, warts (papilloma), nodules, pustules, blisters, lumps and rashes developing on teats, heads, necks, dorsal, feet, face etc. skin and ¾ mucosa of dairy cattle as a result of bovine papilloma virus. Among these were 150 portion of lanolin, 8 portion of Coluber jugularis jugularis molt and 42 portion of isopropyl alcohol (99.8 %). S ince this pomade was prepared with 2% active substance, for dogs, we are able to treat canine oral papillomatosis clinical symptoms (warts seen on lips, cheeks, tongue, palate, gingiva etc.) created by canine ¾Ί papillomavirus and for goats, we can treat ecthyma clinical symptoms (keratitis, hyperkeratosis, orfs, pustules, blisters, lumps and rashes seen on lips, buccal cavity, gingiva, foot coronary band and teats etc.) created by parapoxvirus.
The first pomade is prepared as following;
3¾ I The Coluber jugularis jugularis molt was taken completely. Because this molt was so hard, it was crushed 3 times in forage chopping mixer for one minute.
I After a sketchy crushing process, the molt was crushed and slenderized in thin wire screen by compressing the porcelain mortar handle.
I The pulverized active substance (Coluber jugularis jugularis molt) was taken ttl into a tared glass beaker and its weight was stated in grams on microbalances.
I After adding the formulated lanolin into the porcelain mortar, the active substance (Coluber jugularis jugularis molt) was poured on lanolin as the amount in the formula. Lanolin and active substance was mixed thoroughly.
I 99.8% isopropyl alcohol was added in the mixture of lanolin and active substance as the amount in the formula by the help of a glass pipette and mixed. The formulation was prepared with this methodology.
The first formulation was kept in room temperature. The pomade has semi ttl fluidity in room temperature, it is odorous and it has fine powder specialty when applied on the skin. No irritation after a fleeting paresthesias, inflammation and rash was seen following the application on sensitive skin such as teats. C hemical and pharmacological features:
C hemical and pharmacological features of the raw material used in the first formulation are as following:
The Coluber jugularis jugularis molt: Coluber (=Hierophis) jugularis jugularis, ¾ 1758. It is also named as Karay lan (Blacksnake). It is highly common from
S outheast E urope to S outhwest Asia. In our country, it lives in Aegean, Mediterranean and S outheast Anatolia regions. They move incredibly fast, they are aggressive, biting and non-poisonous. The head part of this snake is characteristic and the neck part may be slightly characteristic. The upper part of the head is ¾Ί covered with bright scales. E ach of these scales carries apical pores. The tip of the rostrum is sharp and rostral plate can easily be seen from the upper side. Out of the two praeoculare, the upper one might be large and divided, and the lower one is quite small. Postocularia is rarely three but usualy two, and subralabialia is rarely seven but mostly eight. They have 19 lines of non-keeled dorsal scales. Ventralia has ¾ 189-220 scales and subcaudalia has 99-128 scales. The upper part of the body of adults is usually uniform bright black. There are no round black spots on the sides of the neck. The lower part of the body of adults has red spots scattered over black or black spots scattered over red surface. The dorsal part is brown, olive or yellowish grey, and they have dark spots. The ventral surface of the youngsters has blackish spots.
The Coluber jugularis jugularis molt used in the study corresponds with epidermis layer of the skin. This layer is found on body surface and is released in nature by molting (relining) periodically. The epidermal layer is composed of Oberh^tchen (cuticle layer), <f-layer, mesos layer, -layer, lacunar tissue and clean layers as outside-in. C uticle and ^-layers face outer surface, and they are hard, strong, nonflexible and soft, -layer is the flexible inner layer. and <f keratin distribution is regarded in snake epidermis. The chemical structure of ^-keratin molecule has been proved to be harder and not more elastic compared to -keratin. S ince high levels of ^-keratin is found in the skin, it is believed to be protective ttl against outer injuries, -keratin is thought to provide flexibility for the skin. When snake epidermises were studied chemically, various enzymes were found. These enzymes were produced from lacunar layer and live cellular layers. 8 different enzymes played an important role in differentiation of and mesos layers. There is no information about specific enzyme functions of keratinocytes. Besides, lipids and other components take part in skin composition.
Lanolin: (Lanoline, G raisse de Laine, Adeps lanae-Refined Wool Oil-Lanae cera-Lanoleine): It is obtained from sheep wool. It is light yellow and pasty. It is ¾ dissolved in ether, petrol ether, chloroform and hot alcohol. It absorbs water twice its weight. It is emulgator. It performs water/oil emulsion. Its consistence is hard without water. When water is added, it becomes pasty. It absorbs water at its weight. It is absorbed easily by skin. It is non-flavored. It is used as excipient.
Isopropyl alcohol (99.8%): It is a clear, flammable alcohol with an odour of ¾Ί ethanol and acetone mixture. It creates a solution at all rates in water, ethanol, acetone, chloroform and benzene. It has a colorless fluid appearance. C3H8O is the chemical formula. It is also known as isopropanol. It is used as a solvent in purification and extraction of natural products. It is also used in purification, crystallization and precipitation of organic chemicals.
¾ S ince the Coluber jugularis jugularis molt has various substances and enzymes in its epidermal structure, our pomade has great importance for it heals keratitis, hyperkeratosis, pustules, blisters, lumps and rashes created by viruses on skin and mucosal structures and for it hinders the viral replication within the cell or provides death.
Lanolin provides a decisive, homogenous and smooth emulsion in the formulation by ensuring a good mixture of alcohol and Coluber jugularis jugularis molt. It also provides the easy absorption of Coluber jugularis jugularis molt by the skin and its permanence.
Isopropyl alcohol is used as a solvent in purification and extraction of Coluber jugularis jugularis molt.
Blood leukocyte samples from 25 dairy cattle that were suspected to have been infected by bovine papilloma virus and used in the study were studied by E LISA test in terms of bovine papilloma virus antigen presence. Bovine papilloma virus antigen presence was found positive in all animals. In wart tissue samples from three ttl of these animals, Bovine papilloma virus genome presence was studied by PC R test.
Bovine papilloma virus genome presence was found positive in all animals.
Tissue or swap samples taken by swap from 10 goats that were suspected to have ecthyma and used in the study were studied by Real-Time PC R in terms of parapoxvirus presence. Parapoxvirus was found positive in all animals. Blood leukocyte samples from 5 dogs that were suspected to have been infected by canine oral papilloma virus and used in clinical studies were studied by E LISA test in terms of canine oral papillomavirus antigen presence. Canine oral papillomavirus antigen presence was found positive in all dogs. Canine oral ¾ papillomavirus genome presence in blood leucocyte samples from 3 of these animals was studied by PC R test. Canine oral papillomavirus genome presence was found positive in all animals. Mouth papilloma sample from 1 of these animals was studied by electron microscopy and canine oral papillomavirus presence was monitored.
Using our second pomade formulation, keratitis, hyperkeratosis, warts ¾Ί (papilloma), nodules, pustules, blisters, lumps and rashes appearing on teat, head, neck, dorsal, foot and face etc. skin and mucosa of dairy cattle as a result of papillomavirus were treated. Canine oral papillomatozis clinical symptoms of canine papillomavirus in dogs (warts seen on lips, cheeks, tongue, palate, gingiva etc.) and ecthyma clinical symptoms of parapoxvirus in goats (keratitis, hyperkeratozis, orfs, ¾¾ pustules, blisters, lumps and rashes appearing on areas such as lips, buccal cavity, gingiva and foot coronary band and teats etc.) were treated. Our second pomade formulation with 4% active substance is composed of 75 portion of lanolin, 75 portion of Vaseline, 8 portion of Coluber caspius molt, 21 portion of isopropyl alcohol (99.8%) and 21 portion of ether. Our second pomade formulation was used for keratitis, hyperkeratosis, orfs, nodules, pustules, blisters, lumps and rashes appearing on sensitive areas such as teat and mouth skin and mucosa.
The second pomade is prepared as following;
I Coluber caspius (Hazer snake, G ray Yuruk) molt was taken completely.
Because this molt was so hard, it was crushed 3 times in forage chopping mixer for one minute.
I The roughly crushed molt was crushed and slenderized in thin wire screen by compressing the porcelain mortar handle.
I The pulverized active substance (Coluber caspius molt) was taken into a tared ti glass beaker and its weight was stated in grams on microbalances.
I 21 ml. of 99.8% isopropyl alcohol and 21 ml. of 99.5% diethyl ether were added into a porcelain mortar. The pulverized active substance (Coluber caspius molt) was poured on it and mixed. l Following the melting period of active substance (Coluber caspius molt), 75 grams of lanolin was added in the mixture and mixed. 75 grams of Vaseline (white) was added in the last composition and it was mixed by porcelain mortar handle thoroughly and was homogenized. The second formulation was ¾ prepared with this methodology.
The second formulation mixture was kept in room temperature. The pomade has semi fluidity in room temperature, it is odorous and it has fine powder specialty when applied on the skin. No irritation after a fleeting paresthesias, inflammation and ¾Ί rash was seen following the application on sensitive skin such as teats.
C hemical and pharmacological features:
C hemical and pharmacological features of the raw material used in the second formulation are as following:
¾¾ The Coluber caspius molt: C oluber (=Hierophis) caspius G ME LIN, 1789. It is also named as Hazer snake and G ray Yuruk. It is mostly seen around Balkan countries, S outhern Russia and Caucasia. In our country, it lives in Thracian, Aegean, Mediterranean, Western Black S ea and Central Anatolia regions. This snake has a high biting tendency and is non-poisonous. The head part is large and the neck part is narrow. It may grow up to 180 centimeters. The dorsal scales are flat and rarely slightly keeled. There are two holes at the tip of each scale. The number of scales around the body is 19, but rarely 17. The number of scales on its skin ventral varies between 190-215 and between 90-113 on subcaudal. This snake does not have black spots on sides of its neck. The lower part of its body is yellowish white, spotless and sometimes there are thin black spots beneath the tail. The dorsal part is grey-brown, olive or yellowish grey. The middle part of dorsal scales has a lighter color than the edges. There are no thin white lines on the edges. The upper part of the head is mostly refractory brown, dark spotted or sometimes grey/dark brown.
The Coluber caspius molt used in the study corresponds with the epidermis ttl (upper skin) layer of the skin. This layer is located on body surface and is released in nature for molting (relining) periodically. The epidermal layer is composed of Oberh^tchen (cuticle layer), <f-layer, mesos layer, -layer, lacunar tissue and clean layers as outside-in. C uticle and ^-layers face outer surface, and they are hard, strong, nonflexible and soft, -layer is the flexible inner layer. and <f keratin distribution is regarded in snake epidermis. The chemical structure of ^-keratin molecule has been proved to be harder and not more elastic compared to -keratin. S ince high levels of ^-keratin is found in the skin, it is believed to be protective against outer injuries, -keratin is thought to provide flexibility for the skin. When ¾ snake epidermises were studied histochemically, various enzymes were found.
These enzymes were produced from lacunar layer and live cellular layers. 8 different enzymes played an important role in differentiation of and mesos layers. There is no information about specific enzyme functions of keratinocytes. Besides, lipids and other components take part in skin composition.
¾Ί Lanolin: (Lanoline, G raisse de Laine, Adeps lanae-Refined Wool Oil-Lanae cera-Lanoleine): It is obtained from sheep wool. It is light yellow and pasty. It is dissolved in ether, petrol ether, chloroform and hot alcohol. It absorbs water twice its weight. It is emulgator. It performs water/oil emulsion. Its consistence is hard without water. When water is added, it becomes pasty. It absorbs water at its weight. It is ¾ absorbed easily by skin. It is non-flavored. It is used as excipient.
Vaseline: (paraffinum album, Vaseline blanch, vaselinum album, petrolatum album): It is an oily excipient providing a moisturizing effect on the skin and used for skin care and treatment of skin irritation. It is obtained from the remainder substance after petrol distillation. It is formed by whitening soft yellow paraffin. It is not dissolved in water but is dissolved in alcohol slightly and easily in ether, chloroform, benzole, essence and oil. It is not absorbed, does not cause irritation and is used as pomade excipient. It is odourless and tasteless.
Isopropyl alcohol (99.8%): It is a clear, flammable alcohol with an odour of ethanol and acetone mixture. It creates a solution at all rates in water, ethanol, acetone, chloroform and benzene. It has a colorless fluid appearance. C3H8O is the chemical formula. It is also known as isopropanol. It is used as a solvent in purification and extraction of natural products. It is also used in purification, crystallization and precipitation of organic chemicals.
Isopropyl alcohol is used as a solvent for purification and extraction of C oluber ttl caspius molt. It functions as a solvent. Alcohol shows its effect by coagulating proteins and melting lipids.
Ether (Aether, Ether anesthesicus, Diethyl ether, Ether sulfurique, Ether T.K.): It is diethyl ether supplemented by antioxidants. It is a clear, colorless, volatile, easily flammable, characteristic scented and highly quick fluid. The boiling point is 34-35 eC . It is dissolved in water between 1 :12 and 15. It mixes in alcohol, chloroform, methylene chloride, petrol ether, stable and volatile oils. 93 drops weigh 1 gram. It has a myorelaxant effect.
S ince the Coluber caspius molt has various substances and enzymes in its ¾ epidermal structure, our pomade has great importance for it heals keratitis, hyperkeratozis, pustules, blisters, lumps and rashes created by viruses on skin and mucosal structures and for it hinders the viral replication within the cell or provides death.
Lanolin provides a decisive, homogenous and smooth emulsion in the ¾Ί formulation by ensuring a good mixture of alcohol and Coluber caspius molt. It also provides the easy absorption of Coluber caspius molt by the skin and its permanence.
Vaseline is the last supplemented component in the formula. It was used to increase the absorption of active substance at body temperature from the skin and ¾ mucosal surface. It also has a softener effect.
Diethyl ether, together with alcohol, performs as a solvent in purification and extraction of Coluber caspius molt and increases its efficiency. It also plays an important role in deeper penetration of active substance from antioxidant and skin and muscle layers.
Blood leukocyte samples from 50 dairy cattle that were suspected to have been infected by bovine papillomavirus and used in the study were studied by E LISA test in terms of bovine papillomavirus antigen presence. Bovine papillomavirus antigen presence was found positive in all animals. In wart tissue samples from 15 of these animals, Bovine papillomavirus genome presence was studied by PC R test. BPV genome presence was found positive in all animals.
Tissue or swap samples taken by swap from 20 goats that were suspected to have ecthyma and used in the study were studied by Real-Time PC R in terms of parapoxvirus presence. Parapoxvirus was found positive in all animals.
Blood leucocyte samples from 20 dogs that were suspected to have been ttl infected by canine oral papilloma virus and used in clinical studies were studied by E LISA test in terms of canine oral papillomavirus antigen presence. Canine oral papillomavirus antigen presence was found positive in all dogs.
Using our third pomade formulation, really hard and large keratitis, hyperkeratosis, warts (papilloma), nodules, pustules, blisters, lumps and rashes appearing on teat, head, neck, dorsal, foot and face etc. skin and mucosa of dairy cattle as a result of papillomavirus were treated. Our third pomade formulation with 4% active substance is composed of 70 portion of lanolin, 70 portion of vaseline, 8 portion of Coluber caspius molt, 27 portion of isopropyl alcohol (99.8%), 8 portion of ¾ glacial acetic acid, 2 grams of podophyllin (1 %) and 15 portion of ether.
The third pomade is prepared as following;
I Coluber caspius (Hazer snake, G ray Yuruk) molt was taken completely.
Because this molt was so hard, it was crushed 3 times in forage chopping mixer for one minute.
¾Ί i The roughly crushed molt was crushed and slenderized in thin wire screen by compressing the porcelain mortar handle.
I The pulverized active substance (Coluber caspius molt) was taken into a tared glass beaker and its weight was stated in grams on microbalances.
I 8 grams of pulverized active substance (Coluber caspius molt), 27 ml. of ¾ 99.8% isopropyl alcohol and 15 ml. of 99.5% diethyl ether was simultaneously added into a porcelain mortar. The mixing process was performed by a porcelain mortar and active substance (Coluber caspius molt) was made to melt completely.
I Following the melting period of active substance (Coluber caspius molt), 8 grams of glacial acid and 70 grams of lanolin was added in the mixture and mixed.
I 2 grams of podophyllin was added in the composition and it was homogenized by thoroughly mixing with a porcelain mortar handle.
I Vaseline (white) was added in the last composition and it was mixed by porcelain mortar handle. The third formulation was prepared with this methodology.
The third formulation mixture was kept in room temperature. The pomade has semi fluidity in room temperature, it is acidic odorous and it has fine powder speciality ttl when applied on the skin. Irritation was seen after a fleeting paresthesias, inflammation and rash following the application on sensitive skin such as teats. Therefore, we recommend the pomade to be used for really hard and large keratitis, hyperkeratosis and wart (papilloma) formations appearing on teat, head, neck, dorsal, foot and face etc. skin and mucosa. We also recommend it not to be used on teats, face and eyes, and even if it should be used, limited application should be regarded. In case of any irritation, inflammation and rashes, washing the area with water is recommended. In this kind of cases, water wash may be possible in four ¾ hours after applying the pomade.
C hemical and pharmacological features
C hemical and pharmacological features of the raw material used in the third formulation are as following:
¾Ί The Coluber caspius molt: C oluber (=Hierophis) caspius G ME LIN, 1789. It is also named as Hazer snake and G ray Yuruk. It is mostly seen around Balkan countries, S outhern Russia and Caucasia. In our country, it lives in Thracian, Aegean, Mediterranean, Western Black S ea and Central Anatolia regions. This snake has a high biting tendency and is non-poisonous. The head part is large and ¾ the neck part is narrow. It may grow up to 180 centimeters. The dorsal scales are flat and rarely slightly keeled. here are two holes at the tip of each scale. The number of scales around the body is 19, but rarely 17. The number of scales on its skin ventral varies between 190-215 and between 90-113 on subcaudal. This snake does not have black spots on sides of its neck. The lower part of its body is yellowish white, spotless and sometimes there are thin black spots beneath the tail. The dorsal part is grey-brown, olive or yellowish grey. The middle part of dorsal scales has a lighter color than the edges. There are no thin white lines on the edges. The upper part of the head is mostly refractory brown, dark spotted or sometimes grey/dark brown.
The Coluber caspius molt used in the study corresponds with the epidermis (upper skin) layer of the skin. This layer is located on body surface and is released in nature for molting (relining) periodically. The epidermal layer is composed of Oberh^tchen (cuticle layer), <f-layer, mesos layer, -layer, lacunar tissue and clean layers as outside-in. C uticle and ^-layers face outer surface, and they are hard, strong, nonflexible and soft, -layer is the flexible inner layer. and <f keratin ttl distribution is regarded in snake epidermis. The chemical structure of ^-keratin molecule has been proved to be harder and not more elastic compared to -keratin. S ince high levels of ^-keratin is found in the skin, it is believed to be protective against outer injuries, -keratin is thought to provide flexibility for the skin. When snake epidermises were studied histochemically, various enzymes were found. These enzymes were produced from lacunar layer and live cellular layers. 8 different enzymes played an important role in differentiation of and mesos layers. There is no information about specific enzyme functions of keratinocytes. Besides, lipids and other components take part in skin composition.
¾ S ince the Coluber caspius molt has various substances and enzymes in its epidermal structure, our pomade has great importance for it heals keratitis, hyperkeratosis, pustules, blisters, lumps and rashes created by viruses on skin and mucosal structures and for it hinders the viral replication within the cell or provides death.
¾Ί Lanolin: (Lanoline, G raisse de Laine, Adeps lanae-Refined Wool Oil-Lanae cera-Lanoleine): It is obtained from sheep wool. It is light yellow and pasty. It is dissolved in ether, petrol ether, chloroform and hot alcohol. It absorbs water twice its weight. It is emulgator. It performs water/oil emulsion. Its consistence is hard without water. When water is added, it becomes pasty. It absorbs water at its weight. It is ¾ absorbed easily by skin. It is non-flavored. It is used as excipient.
Lanolin provides a decisive, homogenous and smooth emulsion in the formulation by ensuring a good mixture of alcohol and Coluber caspius molt. It also provides the easy absorption of Coluber caspius molt by the skin and its permanence.
Vaseline: (paraffinum album, Vaseline blanch, vaselinum album, petrolatum album): It is an oily excipient providing a moisturizing effect on the skin and used for skin care and treatment of skin irritation. It is obtained from the remainder substance after petrol distillation. It is formed by whitening soft yellow paraffin. It is not dissolved in water but is dissolved in alcohol slightly and easily in ether, chloroform, benzole, essence and oil. It is not absorbed, does not cause irritation and is used as pomade excipient. It is odourless and tasteless.
Isopropyl alcohol (99.8%): It is a clear, flammable alcohol with an odour of ethanol and acetone mixture. It creates a solution at all rates in water, ethanol, acetone, chloroform and benzene. It has a colorless fluid appearance. C3H8O is the ttl chemical formula. It is also known as isopropanol. It is used as a solvent in purification and extraction of natural products. It is also used in purification, crystallization and precipitation of organic chemicals. Isopropyl alcohol is used as a solvent for purification and extraction of C oluber caspius molt. It functions as a solvent. Alcohol shows its effect by coagulating proteins and melting lipids.
Ether (Aether, Ether anesthesicus, Diethyl ether, Ether sulfurique, Ether T.K.):
¾ It is diethyl ether supplemented by antioxidants. It is a clear, colorless, volatile, easily flammable, characteristic scented and highly quick fluid. The boiling point is 34-35 eC . It is dissolved in water between 1 :12 and 15. It mixes in alcohol, chloroform, methylene chloride, petrol ether, stable and volatile oils. 93 drops weigh 1 gram. It has a myorelaxant effect.
¾Ί Diethyl ether, together with alcohol, performs as a solvent in purification and extraction of Coluber caspius molt and increases its efficiency. It also plays an important role in deeper penetration of active substance from antioxidant and skin and muscle layers.
G lacial acetic acid (G lacial acetic acid, ethanoic acid, concentrated acetic acid, ¾ E ssigsaure-Acetique acide glacial F P): It is an antibacterial and antifungal agent.
Dense acetic acid burns the skin, gives permanent damage to the eyes and causes blisters on the skin. The effects are felt a few hours later. Glacial acetic acid is in the form of semi-transparent crystals or a sharp scented colorless fluid. The boiling point is between 1 17-1 18 eC . It mixes with water, alcohol, methylen chloride and glycerin. pH is between 2.8-3.4.
In the formulation, glacial acetic acid was used on the purpose of antibacterial, antifungal, astringent (tissue shrinker) and escharotics (burning, corrosive) applications.
Podophyllin: (Podofillum, Podofilino, Podophillinum, Podophyllum rhizome, wild mandrake): Podophyllin is a topical cytotoxic agent. For humans, it is used in treatment of genital warts and other papillomas. Podophyllin resin shows an antimitotic effect and is mainly used in treatment of anogenital warts (kondiloma akuminata). In our country, it is used in treatment of veneral and common benign warts, granuloma inguinale and plantar warts. It was approved in 1945 in USA by ttl F DA and on April 3rd 2008 in T urkey to be used for treatment of human papillomas.
In the formulation, podophyllin assists the active substance and shows its effect by fundamentally stopping the mitotic division during metaphase. Thus, the basic effect of podophyllin depends on its primary acantholytic characteristic. The tumor undergoes exfoliation as a consequence. Dense morphological changes appear in epithelial cells. Podophyllin stops the mitosis in epithelial cells during metaphase. This substance is effective on warts that store less keratin. It does not create a lytic effect beyond epidermal cell layer. It has minimal effect on corium layer. It does not leave any scars in topical applications. Podophyllin which is applied ¾ topically has no systematic effect.
Blood leukocyte samples from 10 dairy cattle that were suspected to have been infected by bovine papillomavirus and used in clinical studies were studied by E LISA test in terms of bovine papillomavirus antigen presence. Bovine papillomavirus antigen presence was found positive in all animals. In wart tissue ¾Ί samples from 10 of these animals, bovine papillomavirus genome presence was studied by PC R test, bovine papillomavirus genome presence was found positive in all animals.
3¾
tti til

Claims

C LAIMS
1. A topical pomade developed against warts (papillomas) appearing as a result of virus infections in animal skin and mucosa characterized by ¾ comprising at least one of Coluber jugularis jugularis (Black snake) and
Coluber caspius (Hazer snake, G ray Yuruk) molt powders.
3&
tin til
PCT/TR2018/050387 2017-08-10 2018-07-20 Topical pomade developed for warts (papilloms) and orfs appearing as a result of virus infections in animal skin and mucosa WO2019098960A2 (en)

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CN102379963B (en) * 2010-09-03 2013-04-17 李兴阜 Skin wound treating ointment and preparation method thereof
CN104189189B (en) * 2014-09-13 2016-04-13 蒋世芬 Caput Felis domestica, Periostracum Serpentis are cured the wound combination medicine
CN105169158A (en) * 2015-09-18 2015-12-23 庞群 External coating ointment for burns and scalds
CN105434870A (en) * 2015-12-24 2016-03-30 张彬彬 Externally used ointment for treating burns and scalds
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