TARIFNAME SARIÇIÇEKLI ORMANGÜLÜ (RHODODENDRON LUTEUM) ILE AGRI KESICI KOLD KREM YAPIMI Teknolojik alan: Mevcut bulus romatizmal agrilarin azaltilmasi için gelistirilmis,dogal içerige sahip karadeniz bölgesinin endemik bitkisi olan sari çiçekli orman gülü( rhododendron luteum ) ekstresi kullanilarak gelistirilmis cilt kremi ile ilgilidir. Teknigin bilinen durumu: Romatizma kelimesi, Yunanca "rheuma" kökünden gelir. Bu kelime "akma"yi dolayisi ile etrafindaki agri veya aciyi ifade etmek için kullanilir. Romatizma deyince tek bir hastalik anlasilmaz. 100\'den fazla hastaligi içerir. Bazilari sik bazilari ise oldukça nadir görülür. Artritin kelime anlami vücuttaki bir veya daha fazla eklemde görülen yangidir. Artrit çocuklar da dahil olmak üzere herkesi her yasda etkileyebilir, bununla beraber kadinlarda erkeklere göre bu hastaliklara yakalanma sansi daha fazladir. Eklemler bir kemigi digerine baglar ve kemiklerin serbestçe hareket edebilmelerine izin verecek sekilde tasarlanmislardir. Kemiklerin son bölümünde eklemler kikirdak olarak adlandirilan sert, lastik kivaminda bir materyal ile örtülmüslerdir. Biz yaslandikça bu eklem kikirdagi sik kullanmaya bagli veya yaralanmalardan sonra daha kolay zedelenebilir hale gelir. Temel olarak 2 tip romatizma vardir: 1. Iltihabi olanlar 2. Iltihabi olmayanlar. l) Iltihabi olanlar: Romatizmal iltihap 3 çesittir: a) Mikroplarin eklemde oturmasiyla ortaya çikan mikrobik romatizmalar: Stafilokok, streptokok ve tüberküloz basili gibi çesitli mikroplar bu romatizmaya neden olur. b) Bagisiklik sisteminin bozuk olusu sonucu gelisen mikropsuz iltihap: Bu tip iltihabin neden oldugu romatizmalarin en önemlileri romatoid aitrit (RA), ankilozan spondilit (AS) ve yaygin bag doku iltihabi yapan hastaliklar (kollajen hastaliklar)'dir. Bu son grubun en iyi bilinen örnegi de sistemik lupus eritematozus (SLE)'dur. c) Diger bir iltihap tipi de basta ürik asit olmak üzere diger kristallerin eklemlerde ve çesitli dokularda oturarak yaptigi tahris sonucu ortaya çikan iltihaptir. Gut ve yalanci gut hastaliginda bu tip iltihap vardir. 2) Iltihabi olmayan romatizmalar: Bu romatizmalarin en önemlisi aitroz (kireçlenme)'dur. Artrozda eklemde iltihap yoktur. Buna karsilik asinma vardir. Eklemin içindeki kikirdak incelir ve kaybolur, eklemlerin kenarlarinda kemik çikintilari olusur. Travmalar (kaza, darbe) mekanik nedenler, metabolik ve psikolojik bozukluklar iltihabi olmayan romatizmalarin en önemli nedenleridir. TR 2010/ 07847 numarali ve "Romatizma kürü ve hazirlama yöntemi " baslikli patent basvurusuna konu olan diger bir bulustur.Bulus saglik sektöründe uygulanan ve sifali bitkileri kullanarak hazirlanan dogal ve bitkisel çaylar ile uygulanan bir romatizma kürü ile ilgili olup bizim bulusumuz ile amaç olarak benzerlik gösterse de uygulama yöntemi olarak farklidir. TR 2003/01083 numarali ve " Kireçlenme romatizma ve siyatigin yani sira selülit ve ekleme rahatsizliklarini iyilestiren masaj kremi" baslikli patent basvurusunda konu olan diger bir bulustur.Bulus insan vücudunda sirt,basen,ayaklar ve el parmaklarindan dirseklere kadar kireçlenme,romatizma ve siyatigin yani sira selülit ,eklem rahatsizliklari ve bel fitigi tedavisinde masaj kurallari ile deriye sürülmesi yöntemiyle kullanilan organik terkiplerle ilgili olup etken madde içerikleri bizim bulusumuzun içerigi ve etken maddesiyle tamamen farklidir. TRl999/02486 numarali ve "Etken maddesini Aescin,in (At kestanesi tohumu) olusturdugu antiromatizmal surup " baslikli patent basvurusunda konu olan diger bir bulustur.Bulus At ketanesi tohumunda buluna maddelerden birisi olan Aescin maddesini temel alarak (%80 proesigenol ve %20 barrin togenol C) olusturulmustur.Içerik olarak bizim bulusumuzdan tamamen farklidir. Sonuç olarak gerek koruma altindaki kremler gerek piyasadaki kremlerin içerikleri , formülasyonlari ve üretim yöntemleri kremimizle farklidir. Bulusun amaci: Mevcut bulus yukarida bahsedilen gereksinimleri karsilayan, tüm dezavantjlari ortadan kaldiran ve ilave bazi avantajlar getiren romatizmal agrilarin azaltilmasinda kullanilmak üzere gelistirilmis, dogal içerige sahip bir cilt kremi ile ilgilidir. Ormangülü (Rhododendron) geleneksel tipta kullanilan bitkilerdendir. Özellikle Mor ve Sari çiçekli ormangülü türleri bronsit, dis agrilari, artirit ve romatizma agrilari gibi hastaliklarda tedavi amaçli kullanilmaktadir. Bunun sonucunda amaç Türkiye de Dogu Karadeniz bölgesinde yetisen Sari çiçekli orman gülünün yapragi ve tomurcugu ile elde edilen ekstreden antibakteriyel testler yapilarak günlük hayatta kullanilabilir, özellikle romatizma agrilari için agri kesici bir krem yapmaktir. Bulusun amaci ,cilt kreminin tamamen dogal içerige sahip olmasi sayesinde hastalar için kullanim güvenliginin saglanmasidir. Bulusun yapisal ve karakteristik özellikleri ve avantajlari asagida verilen detayli açiklama satesinde daha net olarak anlasilacaktir. Bulusun detayli açiklamasi: Bu detayli açiklamada ,bulus konusu romatizmal agrilarin azaltilmasinda kullanilmak üzere gelistirilmis dogal içerige sahip cilt kremi konunun daha iyi anlasilmasina yönelik olarak anlatilmaktadir. Ormangülleri (Rhododendron) kuzey yarim kürenin büyük bir kismini kaplayan vasküler bitkilerin en büyük cinslerinden biridir. Çin, Tibet, Burma, Nepal, Yeni Gine, Tropik Asya, Avrupa ve Kuzey Amerika'da yayilis gösteren 700 türe sahiptir. Türkiye,de Bati Karadeniz,den Dogu Karadenizae kadar sahil ormanlari veya ormanlar arasindaki açikliklarda yayilis gösterir. Ülkemizde 5 türü ile bu türlere bagli 12 taksonu bulunmaktadir. Ülkede en genis alanlara yayilan türleri ise mor çiçekli (R. ponticum) ve sari çiçekli (R. luteum) ormangülleridir. Ormangülleri Dünyanin birçok yerinde fitoterapide kullanilmaktadir. Agri kesici, idrar söktürücü, romatizma agrilarini giderici etkileri mevcuttur. Avrupa da kas agrisi, romatizmal agrilar ve hipertansiyonda kullanilirken Türkiye de özellikle Sari çiçekli ormangülü romatizmal agrilari gidermek amaciyla kullanilir. Kold krem balmumu, su ve belirli yaglarin kombinasyonudur. Fitoterapide bitkiler için krem bazi olarak kullanilmaktadir. Çalismanin amaci, sari çiçekli ormangülünün ekstresi ile kold krem kullanilarak romatizma agrilarini gideren bir krem olusturmaktir ve ekstre ile olusan kold krem formu çalismanin özgünlügünü de yansitmaktadir. Baharda toplanan yapraklar günes isigi almayan bir yerde kurutulmustur. Laboratuvar ortaminda toz halindeki numuneden 31,75 g. Tartilarak üzerine 50 ml etanol eklendi ve agzi kapatildi. Islem tamamlandiktan sonra karisim süzüldü ve çözücü evaporatör ile uzaklastirilmistir. 4.05 g, %13 verim ile orman gülü ekstresi elde edilmistir. Ardindan ekstre ve kold krem ile krem formu olusturulmustur. Krem formu ve ekstreye ayri ayri antibakteriyel test yapilmistir. Olusturulan krem formunun insan sagligi için bir zarari olmadigi görülmüstür. Yöntem Kullanilan Araçlar Heidolph HEI-VAP rotary evaporatör, Ohaus Pionerr hassas terazi, WiseShake SHO-2D otomatik çalkalayici, ECOCELL LSIS-B2V / EC 111 inkübatör, Isotherm mikropipet Sari Çiçekli Ormangülünün Yapragi ve Tomurcugu ile Ekstre Olusturulmasi Bu çalismada kullandigimiz orman gülü (Rhododendron) 2021 yilinin bahar ayinda Giresun yaklasik olarak 2200 rakimda bulunan Kümbet yaylasindan toplanmistir. (Rhododendron) 'un yas yapraklari ve tomurcuklari günes almayan ortamda ve oda sicakliginda gün asiri karistirilmak suretiyle 10 gün kurutuldu. Numunelerin tartimi: Tartimlar plastik bir beher yardimiyla Ohaus Explorer marka hassas terazi kullanilarak gerçeklestirildi. Parçalama islemi: Tartilan numune uygun büyüklükte bir devar kabina koyulduktan sonra üzerine sivi azot dökülerek donduruldu ve havan yardimiyla mümkün oldugunca küçük parçalara ayrildi. Ekstraksiyon islemi: Toz halindeki numuneden 31,75 g. tartilarak 500 mL,lik erlene koyuldu, üzerine 50 ml etanol ilave edildi, agzi septum ile dikkatlice kapatildi ve oda sicakliginda 7 gün otomatik çalkalayici ile karistirildi. Çözeltilerin Eldesi: Ekstraksiyon islemi tamamlandiktan sonra karisim huni yardimiyla filtre kagidindan süzüldü ve çözücü evaporatör vasitasiyla uzaklastirildi. 4.05 g, %13 verim ile orman gülü ekstresi elde edildi ve daha sonra kullanilmak üzere -18 OC, de muhafaza edildi. Kremin Hazirlanisi Cold kremden 10 g. tartildi ve ev tipi mikrodalga sisteminde düsük sicaklikta eritildi. Üzerine hazirlamis oldugumuz ekstreden 0,5 g. eklendi. Soguyuncaya kadar devamli karistirildi ve küçük bir kutuya konuldu. Daha sonra uygun sekilde etiketlenip, krem kivami alincaya kadar buzdolabinda bekletildi. Antibakteriyel çalisma: Çalismamizin bu asamasinda gram negatif (Escheri'chi'a colz' ATCC 25922) ve gram pozitif (Baci'llus cereus ATCC 11778) standart suslari kullanilmistir. Gece boyu büyütülmüs bakteriler, 0,5 McFarland test standardina esdeger bir bulaniklik elde edilecek sekilde seyreltildi ve steril swaplar yardimiyla zikzaglar çizilerek Mueller Hinton besiyeri üzerine homojen sekilde yayildi. Ekstreden steril distile su kullanilarak süspansiyonlar hazirlandi. Petrilerin üzerleri kodlandi ve süspansiyonlardan 100,er ul. bakteri sürülen petriler üzerine damlatildi. Kontrol olarak sadece baz krem süspansiyonu kullanildi. Daha sonra ekstre eklenmis ve eklenmemis kremlerden, bakteri sürülmüs petrilerin ortasina birakildi. Petriler 37°Calik etüVde 18 saat inkübe edildi. Daha sonra petri kaplarinda üreme olup olmadigi gözlemlendi [1]. (K1: baz krem+ekstre; K2: sadece baz krem; El: 0,5g. ekstre +1 g. su; E2: 1g. ekstre+1 g. su) Bulgular Antibakteriyel etki: Kontrolde (K2, baz krem) herhangi bir antibakteriyel aktivite gözlenmemistir. Elde edilen ekstre E. colz' üzerinde antibakteriyel etki göstermemistir. B. cereus üzerinde ise ekstre ve krem formda antibakteriyel aktivite gözlenmistir (K1-E2). Antibakteriyel aktivitenin ekstre konsanstrasyonu ile dogru orantili oldugu görülmüstür (E2E1K1). (Sekil 4) TR TR TR TR TR TR DESCRIPTION MAKING PAIN RELIEF CREAM WITH RHODODENDRON LUTEUM Technological field: The present invention is about a skin cream developed to reduce rheumatic pain, using the extract of yellow flowered rhododendron (rhododendron luteum), which is an endemic plant of the Black Sea region with natural content. Known state of the technique: The word rheumatism comes from the Greek root "rheuma". This word is used to express "flow", hence the pain or suffering around it. Rheumatism is not a single disease. It includes more than 100 diseases. Some are common and some are quite rare. The literal meaning of arthritis is inflammation in one or more joints in the body. Arthritis can affect anyone at any age, including children, although women are more likely to develop these diseases than men. Joints connect one bone to another and are designed to allow bones to move freely. In the last part of the bones, the joints are covered with a hard, rubbery material called cartilage. As we get older, this joint cartilage becomes more easily damaged due to frequent use or after injuries. There are basically two types of rheumatism: 1. Inflammatory ones 2. Non-inflammatory ones. l) Inflammatory ones: Rheumatic inflammation is of 3 types: a) Microbial rheumatisms that occur when microbes settle in the joint: Various microbes such as staphylococcus, streptococcus and tuberculosis bacillus cause this rheumatism. b) Germ-free inflammation that develops as a result of a malfunction of the immune system: The most important rheumatism caused by this type of inflammation are rheumatoid arthritis (RA), ankylosing spondylitis (AS) and diseases that cause widespread connective tissue inflammation (collagen diseases). The best-known example of this last group is systemic lupus erythematosus (SLE). c) Another type of inflammation is the inflammation that occurs as a result of the irritation caused by other crystals, especially uric acid, sitting in the joints and various tissues. This type of inflammation is present in gout and pseudogout. 2) Non-inflammatory rheumatisms: The most important of these rheumatisms is aithrosis (calcification). In arthrosis, there is no inflammation in the joint. On the other hand, there is wear. The cartilage inside the joint becomes thinner and disappears, and bone protrusions form at the edges of the joints. Traumas (accidents, blows), mechanical causes, metabolic and psychological disorders are the most important causes of non-inflammatory rheumatism. It is another invention that is the subject of the patent application numbered TR 2010/ 07847 and titled "Rheumatism cure and preparation method". The invention is related to a rheumatism cure applied in the health sector and prepared with natural and herbal teas using medicinal plants, and although it is similar in purpose to our invention. It also differs in terms of application method. It is another invention that is the subject of the patent application numbered TR 2003/01083 and titled "Massage cream that heals arthritis, rheumatism and sciatica, as well as cellulite and joint disorders". The invention is used in the human body from the back, hips, feet and fingers to the elbows, as well as arthritis, rheumatism and sciatica. It is related to organic compounds used in the treatment of cellulite, joint disorders and herniated disc by applying it to the skin with massage rules, and its active ingredient contents are completely different from the content and active ingredient of our invention. It is another invention that is the subject of the patent application numbered TR1999/02486 and titled "Antirheumatic syrup, the active ingredient of which is Aescin (Horse chestnut seed)". The invention is based on Aescin, one of the substances found in horse chestnut seed (80% proesigenol and 20% barrin togenol). C) was created. It is completely different from our invention in terms of content. As a result, the contents, formulations and production methods of both protected creams and creams on the market are different from our cream. Purpose of the invention: The present invention relates to a skin cream with natural content, developed to be used in reducing rheumatic pain, which meets the above-mentioned requirements, eliminates all disadvantages and brings some additional advantages. Rhododendron is one of the plants used in traditional medicine. Especially purple and yellow flowered rhododendron species are used for treatment purposes in diseases such as bronchitis, toothaches, arthritis and rheumatism pains. As a result, the aim is to make a pain-relieving cream that can be used in daily life, especially for rheumatism pain, by performing antibacterial tests on the extract obtained from the leaves and buds of the Yellow-flowered rhododendron, which grows in the Eastern Black Sea region of Turkey. The purpose of the invention is to ensure the safety of use for patients, thanks to the skin cream having completely natural content. The structural and characteristic features and advantages of the invention will be more clearly understood through the detailed explanation given below. Detailed description of the invention: In this detailed explanation, the skin cream with natural content, which is the subject of the invention and has been developed to be used in reducing rheumatic pain, is described for a better understanding of the subject. Rhododendrons (Rhododendron) are one of the largest genera of vascular plants, covering a large part of the northern hemisphere. It has 700 species distributed in China, Tibet, Burma, Nepal, New Guinea, Tropical Asia, Europe and North America. In Türkiye, it spreads in coastal forests or in the gaps between forests, from the Western Black Sea to the Eastern Black Sea. There are 5 species and 12 taxa related to these species in our country. The species that spread over the largest areas in the country are purple-flowered (R. ponticum) and yellow-flowered rhododendrons (R. luteum). Rhododendrons are used in phytotherapy in many parts of the world. It has analgesic, diuretic and rheumatism pain relieving effects. While it is used for muscle pain, rheumatic pain and hypertension in Europe, in Turkey especially yellow flowered rhododendron is used to relieve rheumatic pain. Kold cream is a combination of wax, water and certain oils. It is used as a cream base for plants in phytotherapy. The aim of the study is to create a cream that relieves rheumatism pain by using kold cream with the extract of yellow-flowered rhododendron, and the kold cream form formed with the extract also reflects the originality of the study. The leaves collected in spring were dried in a place away from sunlight. 31.75 g of the powdered sample in the laboratory environment. It was weighed, 50 ml of ethanol was added and the mouth was closed. After the process was completed, the mixture was filtered and the solvent was removed by evaporator. 4.05 g of rhododendron extract was obtained with 13% yield. Then, a cream form was created with the extract and cold cream. Antibacterial tests were performed separately on the cream form and the extract. It has been observed that the created cream form does not pose any harm to human health. Method Tools Used: Heidolph HEI-VAP rotary evaporator, Ohaus Pionerr precision scale, WiseShake SHO-2D automatic shaker, ECOCELL LSIS-B2V / EC 111 incubator, Isotherm micropipette. Creating Extract with Leaves and Buds of Yellow Flowered Rhododendron. The rhododendron we used in this study. It was collected from Kümbet plateau, located at approximately 2200 altitude in Giresun, in the spring of 2021. The fresh leaves and buds of (Rhododendron) were dried for 10 days in a sun-free environment and at room temperature by mixing every other day. Weighing of the samples: Weighing was carried out using an Ohaus Explorer brand precision scale with the help of a plastic beaker. Shredding process: After the weighed sample was placed in a suitable sized devar container, it was frozen by pouring liquid nitrogen on it and was broken into as small pieces as possible with the help of a mortar. Extraction process: 31.75 g of powdered sample. It was weighed and placed in a 500 mL conical flask, 50 ml of ethanol was added, its mouth was carefully closed with a septum, and it was mixed with an automatic shaker for 7 days at room temperature. Obtaining Solutions: After the extraction process was completed, the mixture was filtered through filter paper with the help of a funnel and the solvent was removed through the evaporator. 4.05 g of rhododendron extract was obtained with 13% yield and was stored at -18 OC for later use. Preparation of the cream: 10 g of cold cream. were weighed and melted at low temperature in a home microwave system. 0.5 g of the extract we prepared on it. added. It was stirred constantly until it cooled and was placed in a small box. It was then labeled appropriately and kept in the refrigerator until it reached a creamy consistency. Antibacterial study: In this phase of our study, gram negative (Escheri'chi'a colz' ATCC 25922) and gram positive (Baci'llus cereus ATCC 11778) standard strains were used. Bacteria grown overnight were diluted to obtain a turbidity equivalent to 0.5 McFarland test standard and spread homogeneously on Mueller Hinton medium by zigzagging with the help of sterile swaps. Suspensions were prepared from the extract using sterile distilled water. The plates were coded and 100 µl of each suspension was added. was dropped onto the petri dishes coated with bacteria. Only the base cream suspension was used as a control. Then, creams with and without added extract were placed in the middle of the petri dishes coated with bacteria. Petri dishes were incubated at 37°C for 18 hours. Then, it was observed whether there was growth in the petri dishes [1]. (K1: base cream+extract; K2: base cream only; Hand: 0.5g. extract +1 g. water; E2: 1g. extract+1 g. water) Findings Antibacterial effect: In control (K2, base cream) no No antibacterial activity was observed. The obtained extract did not show an antibacterial effect on E. colz. Antibacterial activity was observed on B. cereus in extract and cream forms (K1-E2). It has been observed that antibacterial activity is directly proportional to the extract concentration (E2E1K1). (Figure 4) TR TR TR TR TR TR