EP3474873A1

EP3474873A1 - A gynura procumbens oil solution for the treatment of peripheral diabetic polyneuritis, tendinopathies, gingivitis and periodontitis and its process therof

Info

Publication number: EP3474873A1
Application number: EP16784381.2A
Authority: EP
Inventors: Kostas GRIGORIOU
Original assignee: Individual
Current assignee: Individual
Priority date: 2016-06-28
Filing date: 2016-06-28
Publication date: 2019-05-01
Also published as: WO2018001391A1

Abstract

The present invention discloses an innovate and safe method for effective and safe treatment of peripheral diabetic polyneuritis, tendinopathies, and gingivitis - periodontitis, via the topical administration of the gynura procumbens oil solution. The whole invention is based on the cells rejuvenation by the said solution.

Description

A GYNURA PROCUMBENS OIL SOLUTION FOR THE TREATMENT OF PERIPHERAL DIABETIC POLYNEURITIS, TENDINOPATHIES, GINGIVITIS AND PERIODONTITIS AND ITS PROCESS THEROF

Abstract

Introduction

The study provided in this invention disclose the preparation of the Gynura oil solution and the use of it in the treatment of several medical disorders based on the free radical scavenging activity of the polyphenols contained in the said solution and created for this purpose.

The micro molecular properties of the polyphenols contained in gynura procumbens oil solution allow them to penetrate cell membranes of the peripheral nervous system (PNS), tendons and gum tissues, thus becoming able to recover and protect the cells from the destructive free radical activity.

Polyphenols contained in gynura procumbens leaves are bioactive constituents very important in the control and prevention of tissue damage. They protect the cells from oxidative stress that can take place because of the uncontrollable multiplication of the free radicals. Oxidative stress reflects an imbalance between the systemic manifestations of reactive oxygen species and a biological system ability to readily detoxify the reactive intermediates or to repair the resulting damage. Disturbances in the normal redox state of cells can cause toxic effects through the production of peroxides and free radicals that damage all compounds of the cell, including proteins, lipids, and DNA. Oxidative stress from oxidative metabolism cause base damage as well as strand breaks in DNA. Further some reactive oxidative species act as cellular messengers in redox signaling. Thus, oxidative stress can cause oxidative disruption in normal mechanisms in cellular signaling.

Factors causing uncontrolled multiplication of the free radicals

• Infections

• Inflammation

• Prolonged immune response

• Ozone, UV radiation • Pollutants

• Alcohol

• Physical and emotional stress

• Poor nutrition

• Obesity

• Smoking

• Food conservatives

• Temperature variations

• Injuries

• Hypoxia

• Aging

Due to their low molecular weight, polyphenols contained in gynura procumbens leaves penetrate cell membranes and by scavenging and neutralizing free radicals, they eliminate their destructive action on cells membranes, cells proteins and cell's DNA.

Neutralizing the destructive action of the free radicals, by using the gynura procumbens oil solution, the cells function is regulated, the protective mechanisms of the cells are activated and the cells are rejuvenated, thus becoming able to operate as fully functioned cells.

Detailed description of the invention

The present invention provides an innovative, safe, and effective method for treating peripheral diabetic neuropathy, tendonitis and tendinosis, gingivitis and periodontitis by using the oil solution provided from gynura procumbens leaves as topical administration. The said composition is prepared from semi dried leaves collected from a plantation in Limassol Cyprus, created for this purpose.

The whole invention is based on the free radical scavenging activity of the polyphenols contained in gynura procumbens oil solution. By neutralizing the destructive action of the free radicals on cells, their functions recovers, they rejuvenate and multiply, protective mechanisms activate thus becoming fully functioned cells. Preparation of gynura procumbens oil solution

The method introduced herein for the preparation of the gynura procumbens oil solution comprises of drying the leaves in a certain amount of time, heating the leaves in ester for a certain amount of time followed by filtration.

In order to maximize the potency of the said solution 4 variables have been tested.

1) The time in which the solution is heated

2) The temperature in which the solution is heated

3) The time in which the leaves are dried

4) The ester/leaves ratio

The temperatures selected for the for the 1^st variable were 35°C, 50T, 65°C, 80°C and 100°C. The time selected for the 2^nd variable was 2_;4,6,8, 12 hours. Each of these was tested separately. The sample with the greatest potency and an efficient oil infusion was observed when the sample was heated for 8 hours at 65°C.

The biggest difference in the potency of the gynura procumbens oil solution was the amount of time the leaves were dried. Two samples were tested in 2 groups for the treatment of onychomycosis comprising of 15 volunteers where in sample A the leaves were completely dried and in sample B the leaves were semi dried. A and B samples were heated for 8 hours at 65°C.

Sample A had very little medicinal properties when applied topically where sample B had close to 90% cure rate. Based on the above information and results, the final method for creating a gynura procumbens oil solution was formulated along with a clinical study to screen its efficiency.

Process

1. Washing 1 kg of fresh leaves with running water, and then spreading it out indoors on a buzzard fabric which is changed daily to absorb moisture at a room temperature until the weight is reduced to 150gr.

2. Soaking the semi dried leaves in 70% ethanol for sterilization, for 30 minutes.

3. Removing the leaves from ethanol and putting them in a sterile stainless steel container for 30 minutes.

4. Adding two kg of isopropyl myristate and then sealing it with a sterile cap.

5. Incubating in a laboratory thermostat for 8 hours at 65°C.

6. Filtering the solution

For the treatment of gingivitis/periodontitis, olive oil was used instead of isopropyl myristate, following the same process.

EFFICACY IN THE TREATMENT OF SEVERAL MEDICAL CONDITIONS BY GYNURA

SOLUTION

Levels of peripheral nervous system

Merkel cell endings are mechanoreceptors found in the basal epidermis and hair follicles. They are large myelinated nerve endings. They provide information of pressure, position and deep static features such as shapes and edges. Merkel cells in the basal epidermis of the skin store neuropeptides which they release to associate nerve endings in response to pressure. In burns Merkel endings are commonly lost. Each ending consists of a Merkel cell in close opposition with an enlarged nerve terminal. A single afferent nerve fiber branches to innervate up to 90 such endings. Merkel cells are associated with their receptive fields. The receptive field of an individual sensory neuron is the particular region of the sensory space in which a stimulus will trigger the firing of the neuron. Schwan cells are involved in many important aspects of peripheral nerve biology - the conduction of nervous impulses along axons, nerve development, and regeneration, trophic support for nervous, production of the nervous extracellular matrix, and modulation of neuromuscular synaptic activity.

Afferent nerve fiber

In the peripheral nervous system an afferent nerve fiber is the nerve fiber (axon) of a sensory neuron. It is a long process extending far from the nerve cell body that carries nerve impulses from sensory receptors towards the central nervous system. The opposite direction of neural activity is efferent conduction.""" Afferent neurons have a single long axon with a short central and a long peripheral branch. Outside the spinal cord, thousands of afferent neuronal cell bodies are aggregated in a swelling dorsal root known as the dorsal root ganglion. ^IW All the axons in that dorsal root, which contains afferent neuron fibers, are used in the transduction of somatosensory information. All of these sensation travel along the same general pathway towards the brain, from the dorsal root of ganglion they travel to the spinal cord.⁵ From the spinal cord to the medulla, which leeds to the medial lemniscus of the midbrain. From here it travels to the primary somatosensory cortex of the parietal lobe.

Epineurium

Axon is surrounded by the epineurium. Epineurium is the outermost layer of dense irregular connective tissue surrounding a peripheral nerve"' it usually surrounds multiple nerve fascicles as well as blood vessels which supply the nerve. Lymphocytes and fibroblasts are also present and contribute to the production of collagen fibers that form the back born of the epineurium. In addition to providing structural support lymphocytes and fibroblasts play a vital role in maintenance and repair of surrounding tissues.""

Capillars

Capillars surrounded by epineurium are the smallest of the body's blood vessels that make up the microcirculation. Their endothelial linings are only one layer cell thick. They connect arterioles and veins, and they help to enable the water, oxygen, carbon, dioxide and many other nutrients and waste substances between the blood and the tissues"'" surrounding them.

Capillars are protected from the basal lamina, a layer of anchoring fibrils composed of type-VII collagen. Treatment of peripheral diabetic polyneuritis via topical administration of gynura oil solution

Diabetic neuropathies are nerve damaging disorders associated with diabetes mellitus. These conditions are thought to result from diabetic microvascular injury involving blood vessels that supply nerves in addition to macrovascular conditions that can culminate in diabetic neuropathy. Vascular and neural diseases are closely related and intertwined. Blood vessels depend on normal function and nerve depends on adequate nerve flow. The first pathological change in the small blood vessels is narrowing of the blood vessels. As the disease progresses, neural dysfunction correlates closely with blood vessel abnormalities, such as capillary basement membrane thickening and endothelial hyperplasia, which contribute to diminished oxygen tension and hypoxia. Neural ischemia is a well-established characteristic of diabetic neuropathies.

The present study shows that free radical destructive activity causing oxidative stress of the PNS cells, contributes in the development of peripheral diabetic neuropathy. The clinical study as shown below proves that oxidative stress of the cells and tissue of the peripheral nervous system is also involved in the etiology and development of the said disease. Elimination of the oxidative stress caused by the free radicals in several levels of the peripheral nervous system play a critical role in the treatment of the said diabetic complication.

Factors causing oxidative stress due to the multiplication of free radicals present in the peripheral nervous system can be:

1) Poor nutrition caused from diabetic angiopathy

2) Hypoxia

3) Microvascular injury

4) Inflammation

5) Smoking

6) Obesity

7) Aging

Oxidative stress can damage the PNS in the following levels.

1) Oxidative stress causes oxidative disruption in normal mechanisms in cellular signaling.

2) Affected from oxidative stress Merkel cells and Merkel cell endings transmit false information or no information of temperature, pressure, and sense of touch to afferent nerves.

3) Affected from oxidative stress Schwan cells become unable to function properly. 4) Affected afferent nerve fibers (axon) transmit false information from the sensory neurons towards the central nervous system.

5) Affected epineurium cells and tissues become unable to carry their function which is to repair and maintain the afferent nerves surrounding tissues.

6) Affected capillars and their endothelial cells become unable to function properly, causing disturbances in their function which is the microcirculation of the nerves.

Dysfunction of the peripheral nervous system in different levels as prescribed, causes the main symptoms of diabetic polyneuritis which are: Numbness or reduced ability to feel pain or temperature changes, burning sensation, sharp pains or cramps, increased sensitivity to touch, loss of reflexes, loss of balance and coordination and serious foot complications such as ulcers and infections, conditions that can lead to amputation.

1. Results from the use of gynura oil solution via topical administration of gynura oil solution in the treatment of diabetic neuropathy

Due to the ability of the polyphenols contained in the said solution to neutralize the free radicals that damages cells membranes and cell's DNA, the cells function recovered from their destructive action, rejuvenate and multiply, thus becoming fully functioned cells.

Efficacy in the treatment of peripheral diabetic neuropathy by gynura solution is impressive (fig 1). Gynura solution was tested on 45 diabetic patients suffering from peripheral diabetic polyneuritis for a period of less than 5 years. Topical administration to the affected area every 8 hours was practiced. Light massage to the affected area for 5 minutes followed. Symptoms began to subside in 2-4 days. At the beginning of the treatment (1-2 days) the symptoms subside for 1-2 hours after the administration of the solution, and gradually symptoms subside for a longer time. All symptoms disappear in 10-15 days. Supporting treatment was advised by topical application once a day. No side effects and no recurrence of the symptoms were observed.

Results from the treatment via gynura oil solution are illustrated in figure 1 Figure 1

Prior to the treatment of peripheral diabetic neuropathy was rated by the majority of the patients at the severe domain. After the treatment (lasting approximately 12 days) a percentage of 90% rated the symptoms domain at none and a 10% rated the symptoms domain at mild.

Observations during treatment

Positive results appear after the 2^nd day of the treatment. After the topical administration and light massage on the affected area, the intensity of symptoms is reduced for approximately 1 hour and gradually the symptoms subside and disappear in about 10 days

Reappearance of the symptoms of diabetic polyneuritis occurs in a period of a week after discontinuance of the treatment, so patients where advice to follow supporting treatment via the administration of the said solution once daily.

Advantages observed during investigation

1) Safe treatment

2) Easy to use

3) Due to the fast and positive results patients have a higher consistency in following through their treatment

4) No side effects were observed 2.TENDONITIS TENDINOSIS

Main cells and tissues involved in tendinopathies

Tendon

A tendon is a band of fibrous connective tissue that usually connects muscle to bone and is capable of withstanding tension. The collagen portion is made of 97-98% type I collagen with small quantities of other types of collagen. The main cells of the tendon are the tenocytes (elongated fibroblast type cells). Tenocytes produce the collagen molecules which aggregate end-to-end and

side-to-side to produce collagen fibers. Fibril bundles are organized to form fibers with the elongated tenocytes closely packed between them. The cells communicate with each other through gap junctions, and this signaling gives them the ability to detect and respond to the mechanical loading.""

Fibroblast is a type of cell that synthesizes the extracellular matrix and collagen", the structural framework and plays a critical role in wound healing. Fibroblasts are the most common cells in connective tissue. Fibroblasts produce collagen, glycosaminoglycans, reticular and elastic fibers, glycoproteins found in the extracellular matrix and cytokine TSLP. TSLP has been shown to activate the maturation of a specific subset of dendritic cells located within epidermis and called Langerhans cells/' Growing individuals' fibroblasts are dividing and synthesizing ground substance. Tissue damage stimulates fibrocytes and induces the mitosis of fibroblasts.

Extracellular matrix

In biology extracellular matrix (ECM) is a collection of extracellular molecules secreted by cells that provide structural and biochemical support to the surrounding cells."" Fibroblasts are the most common cell type in connective tissue ECM in which they synthesize maintain and provide a structural framework. Due to its diverse nature and composition the ECM can serve many functions, such as providing support, segregating tissues from one another, and regulating intercellular communication. The ECM can exist in varying degrees of stiffness and elasticity. The elasticity of the ECM can differ by several orders of magnitudes. This property is primary depended on collagen and elastin concentration"'" and has recently been shown to play an influential role in regulating numerous cell functions. Proteoglycans

The collagen in tendons is held together with proteoglycans components. Proteoglycans interwoven with the collagen fibrils showing that proteoglycans are important structurally in the interconnection of the fibrils.¹™ The protein component of proteoglycans is synthesized by tenocytes ribosomes and translocated into the lumen of the rough endoplasmic reticulum. Glycosylation of the proteoglycans occurs in the Golgi apparatus in multiple enzymatic steps. The completed proteoglycan is then exported to the extracellular matrix of the tissue. The proteoglycans components of tendons are very important to the mechanical properties. While collagen fibrils allow tendon to resist tensile stress, proteoglycans allow them to resist compressive stress.

TENTINOPATHIES

Tendons are subject to many types of injury. There are various forms of tendinopathies or tendon injuries due to overuse. These types of injuries generally result in inflammation and degeneration or weakening of the tendons which may eventually lead to tendon rupture.¹™

Tendinitis is the inflammation of the tendon and results from micro-tears and that happen when the musculotendinous unit is acutely overload with a tensile force that is too heavy and/or too sudden.

Tendinosis is a chronic degeneration of the tendons collagen in response to chronic overuse; when overuse is continued without giving the tendon time to rest such as with repetitive strain injury, tendinosis results. A microscopic view of tendinosis reveals an increase of immature type III collagen fibers. (Mature type I fibers dominate in healthy tendon tissue), loss of collagen continuity so that collagen fibers are no longer aligned with each other and sometimes fail to line together.

Factors causing multiplication of free radicals and oxidative stress

• Inflammation

• Physical stress

• Poor nutrition

• Hypoxia

• Obesity

• Injuries • Alcohol

• Aging

Cells and tissues affected by oxidative stress caused by free radicals

1) Damage of fibroblast's DNA by free radicals affects the mitosis of the cells which is very important in the process of fibroblast's regeneration.

2) Damage of fibroblast's DNA affects the process of collagen production changing the balance between type I-type III collagen.

3) The said damage affects glycosaminoglycan's production, reticular and elastic fiber production affecting the elasticity of ECM.

4) Affects the production of proteoglycans which occurs in fibroblast ribosomes.

5) Affects the process of the glycosylation of proteoglycans which occurs in the Golgi apparatus.

Topical administrations of the gynura oil solution on the tendon's area release the cells and the tissue of the tendon from free radicals catastrophic activity. Tenocytes recover thus becoming fully functioned cells.

2. Results from the treatment of tendinopathies via topical administration of gynura oil solution

Efficacy of the treatment of tendinitis via topical administration of gynura solution is shown below in figure2. The said treatment was administrated in 65 patients suffering from tendinitis. The said treatment was comprised of topically applying the gynural oil solution 3 times daily followed by light massage to the affected area for 5 minutes.

Results from the treatment of tendinitis are illustrated in figure 2.

Figure 2

Prior to the treatment, acute tendonidis was rated by the majority of the patients at the severe domain. After the treatment (lasting approximately 5 days) a percentage of 95% rated the pain intensity at none and a 5% rated the pain intensity at mild.

Tendinosis

Gynura solution was used via topical administration for the treatment of tendinosis. It was administrated 3 times daily, light massage on the affected area for 5 minutes followed.

Analysis data from this study was the responsibility of the outcome measures was a critical concern. That is, a study with 49 patients tested the effects of the treatment and evaluated the immediate effects. 49 adults rated four domains of intensity / discomfort and evaluated the reliability and validity of four single rating.

Tendinosis was rated by the majority of the patients at the moderate to severe domain.

After the treatment a percentage of 80% evaluated the pain intensity at

40% less on day 10

60% less on day 18

75% less on day 25

80% less on day 30 Results from the treatment of tendinosis via topical administration of gynura oil solution are illustrated in figure 3.

Figure 3

Advantages observed during treatment

1) Safe treatment

2) Easy to use

3) Due to quick and positive results, patients have a higher consistency in completing their treatment

4) No drug interactions or side effects

5) Due to its mechanism of action the solution can be useful in the prevention of tendon raptures.

6) Due to the same mechanism, it can be useful for the prevention of tendon injuries in athletes.

7) Can be used at any age

GINGIVITIS PERIODONTITIS

Main cells and tissues involved in gingivitis and periodontitis

Gingiva is part of the soft tissue lining of the mouth. They surround the teeth and provide a seal around them. Most of the gingiva are tightly bound to them underling bond which helps resist the friction of food passing over them. Gingiva consists of two layers: The surface stratified squamous epithelium, and the deeper Lamina Propria.

Keratinized epithelial cells.

They are found in the gingiva and the primary functions of them are:

1) Protection of the tissues that light beneath it from radiation, desiccation, toxins,

invention by pathogens, and physical trauma.

2) Regulation and exchange of chemicals between the underline tissues and the body cavity.

3) The secretion of hormones into the blood vascular system.

4) To provide thermoregulation.

Lamina propria

Lamina propria is a fibrous connective tissue layer that consists of a network of type I and type III collagen and elastic fibers. The main cells of lamina propria are the fibroblasts, which are responsible for the production of the fibers as well as the extracellular matrix.

Periodontium

Periodontium refers to specialized tissues that both surround and support the teeth, maintaining them in the maxillary and mandibular bones. It provides the support necessary to maintain teeth in function. The periodontium exists for the purpose of supporting teeth during their function and it depends of the stimulation it receives from the function for preservation of its structure. A constant state of balance always exists between the periodontal structure and the external forces.^{xvl ;}

Periodontal ligament

Periodontal ligament is a group of specialized connective tissue fibers that essentially attach a tooth to the alveolar bone within which it sits^x " periodontal ligament undergoes drastic changes with chronic periodontal diseases that involve the deeper structure of the periodontium with periodontitis. The fibers of the periodontium becomes disorganized and their attachments to the alveolar bond proper or cementum are lost because of the resorption of these two hard dental tissues.™" Factors causing multiplication of the free radicals and oxidative stress involved in gingivitis- periodontitis.

• Infections

• Inflammation

• Prolonged immune response

• Smoking

• Alcohol

• Poor nutrition

• Hypoxia

• Food preservatives

• Aging

• Injuries

Gingivitis (inflammation of the gum tissue) is a non-destructive periodontal disease."'* The most common form of gingivitis and periodontal disease is the response to bacterial biofilms (plaque) adherent to tooth surface. In the absence of treatment, or if not controlled, gingivitis can progress to periodontitis, where the inflammation result in tissue destruction and alveolar bon resorption which can ultimately lead to tooth loss.^xx Main symptoms of gingivitis are: swollen gums, bright red gums, painful gums, bleeding or bleeding after brush gums, bad breath called halitosis). When gingiva is swollen the epithelial crevice becomes ulcerated-that condition is called ulcerative gingivitis. Plaque induced gingivitis is by far the most common form of gingival diseases. The etiology of plaque induced gingivitis is bacterial plague which acts to initiate the body's host response. This in turn can lead to destruction of the periodontal attachment apparatus"' the plaque accumulates in the small gaps between the teeth; the bacteria in them produce chemicals and toxins that promote an inflammatory response in the gum tissue.

When the gingiva tissue is not healthy, it can provide a gateway for periodontal disease to advance into the deeper tissue of periodontium, leading to a poorer prognosis for long-term retention of the teeth.

Cells and tissues affected by oxidative stress at gingivitis-periodontitis

1) Epithelial cells

2) Fibroblasts (main cells of lamina propria)

3) Periodontium

4) Periodontal ligament (PDL)

Free radicals penetrate epithelial and fibroblast cell's membrane damaging all structures of the said cells, thus causing oxidative stress. Released from the free radical catastrophic activity, the said cells recover, thus becoming fully functioned cells.

Regulation of the function of gum's epithelial cells, due to the free radical scavenging activity of the gynura procumbens oil solution, regulates and activates the primary function of them which is the formation of a barrier against environmental damage, pathogenic bacteria, fungi, viruses, parasites, heat, physical trauma, and dehydration. Recovered from DNA mutations caused by free radicals, cells multiply, their protective mechanisms reactivate thus becoming fully function cells.

Rejuvenation of fibroblasts-main cells of lamina propria is of crucial importance. The following results are achieved:

1) Recovery of the production of collagen and elastic fiber

2) Improvement of the quality of collagen and the balance between type I— type III collagen

3) Restoration of the balance in proteoglycans production in the extracellular matrix

4) Due to the above mention factors, periodontal ligament surrounding and supporting the teeth recovers thus becoming able to maintain them in the maxillary and mandibular bones.

3. Treatment of gingivitis, ulcerative gingivitis and periodontitis via the topical

administration of gynura oil solution

Olive oil gynura solution was used for the treatment of the above conditions via topical administration in spray form. It was used on 62 patients suffering from gingivitis and on 13 patients suffering from ulcerative gingivitis. It was administrated twice daily after tooth brushing, very light finger massage followed. Results from the said treatment are illustrated in figures 4 and 5.

Results from the treatment of gingivitis and ulcerative gingivitis are illustrated in figure 4 and figure 5 respectivly.

Prior to the treatment, Gingivitis was rated by the majority of the patients at the Moderate to severe domain. After the treatment (lasting approximately 7 days) a percentage of 95% of the patients rated the symptoms and pain domain at none and a 5% rated the pain domain at mild.

The symptoms of ulcerative gingivitis disappear in about 10 days. Periodontitis

Analysis data from this study was the responsibility of the outcome measures was a critical concern. That is, a study with 58 patients tested the effects of the treatment and evaluated the immediate effects.

Gum recession starts to recover in about 1 month and continuous to recover at all treatment period (3-6 months according to the degree of the damage).

Moving teeth starts to recover in 1 month and continuous its recover during treatment. The treatment lasts approximately 3-6 months, according the degree of the damage.

Remarks

1) Main symptoms of gingivitis (swelling gums, bright or purple gums, painful gums,

bleeding gums, halitosis) disappear in 5 days maximum.

2) Symptoms of ulcerative gingivitis disappear in 10 days maximum.

3) Due to the rejuvenation of gingiva's fibroblast, cells gingival recession start to recover after 15-20 days.

4) Periodontal ligament surrounding and supporting the teeth recover, thus becoming able to maintain them in the maxillary and mandibular bones and also start to recover ih about 15-20 days.

5) Intensity of moving teeth begins to subside in 15-20 days and moving teeth gradually becomes fixated.

Conclusions

The present invention can cause fundamental changes in the approach of the treatment of serious medical conditions and diseases like peripheral diabetic polyneuritis, tendonitis - tendinosis and gingivitis - periodontitis.

The present invention can also change our understanding about the pathogenesis of the said conditions.

This invention proves the recovering and rejuvenating ability of the human cells after the neutralization of the free radicals from which are affected. Released from free radicals destructive action cells rejuvenate, thus becoming able to neutralize pathogenic factors from which are affected.

This can be succeeded by using the gynura oil solution. The preparation of it is as prescribed in the present invention.

By using the said method the use of tricyclic antidepressants, SSNRIs, SSRIs, NSAIDs, opioids, synthetic cannabinoids, antiepileptic drugs and anticonvulsants used for the treatment of diabetic polyneuritis can be limited or even avoided and by that, medication toxicities can be avoided. The use of antibiotics can also be limited since the use of gynura solution can prevent the appearance of ulcerations in diabetic patients and prevent amputations.

Effective treatment of periodontitis can save teeth from losing. Also expensive surgical treatments can be avoided.

The use of gynura solution can also be useful in athletes by keeping tendons and muscles in good condition. By using the said solution tendon ruptures can be avoided.

Claims

1. A method of achieving a gynura oil solution via the heating of the semi dried leaves of gynura mixed with - but not limited to - isoprophyl myristate oil, after they have been washed with running water, left to dry then soaked in ethanol for half an hour for sterilization. The said solution is then filtered.

2. A method of achieving a gynura oil solution via the heating of the semi dried leaves of gynura mixed with - but not limited to - olive oil, after they have been washed with running water, left to dry then soaked in ethanol for half an hour for sterilization. The said solution is then filtered.

3. The method of claim 1 includes the heating of the semi dried leaves with - but not limited to - Myristate, Isopropyl Palmitate, Ethylhexyl Stearate, Ethylhexyl Palmitate, Cetearyl Ethylhexanoate, Stearyl Stearate, Isocetyl Stearate, Triglyceride, Propylene Glycol Diester, Glycerine Tri-lsostearate, Decyl Oleate, Decyl Cocoate, Oleyl Oleate, Stearoxy Dimethicone, Cetyl Dimethicone

4. The method of claim 1 can be carried out by heating the semi dried leaves at a temperature between 40°C - 100°C

5. The method of claim 1 includes the drying of leaves and can be carried out by drying the leaves in room temperature until the mass of the leaves is reduced by a ratio of 100 to 15 until the said leaves become semi dried

6. The method of claim 1 includes the drying of the leaves and can be carried out by - but not limited to - using a thermostat

7. The method of claim 1 includes the drying of the leaves and can be carried out by - but not limited to - using Calcium Chloride until the said leaves become semi dried meaning said leaves mass is reduced by a ratio of 100 to 15

8. The method of claim 1 includes the sterilization of semi dried leaves and can be carried out by soaking the said leaves in ethanol for 1 to 60 minutes

9. The method of claim 1 includes the sterilization of semi dried leaves and can be used for any methods of sterilization

10. The method of claim 1 includes infusing the semi dried leaves, wherein the said semi dried leaves have moisture content greater than 10% and less than 70%

11. The composition resulting from the method in claim 1 is used for treating gingivitis periodontitis, tendinosis, tendonitis and peripheral diabetic neuropathy

12. The composition resulting from the method in claim 1 is for the treatment of other types of peripheral neuropathies

13. The composition resulting from the method in claim 1 is for treating

14. The composition resulting from method 1 may be in a spray form

15. The composition resulting from method 1 may be used as an ingredient for ointments, spray, lotions or creams

16. The product of claim 1 further comprising a solution agent

17. The product of claim 1 mixed with antibiotics, NSAIDs and vitamins

18. The product of claim 1 mixed with topical steroids

19. The product of claim 1 mixed with moisturizing cream

20. A liquid composition for treating gingivitis and periodontitis consisting of the following ingredients:

Between about 15-20 ml of gynura oil solution

Between about l-2ml of mint extract

21. The composition according to claim 20 wherein the essential oil is pharmaceutical grade

References

¹ Mader S. S. (2000): Human biology. McGraw-Hill, New York

" Hall J. E., Guyton A. C. (2006): Textbook of medical physiology, 11th edition. Elsevier Saunders, St. Louis, Mo,

m Warrell D. A., Cox T. M., Firth J. D. (2010): The Oxford Textbook of Medicine (5th ed.). Oxford University Press

i^v MacCallum, Don. "Peripheral Nervous System". Histology and Virtual Microscopy Learning Resources. University of Michigan Medical School. Retrieved 24 June 2014.

v Carlson, Neil. Physiology of Behavior. Upper Saddle River, New Jersey: Pearson Education, Inc. ISBN 9780205239399.

vⁱ McCracken, Thomas (1999). New Atlas of Human Anatomy. China: Metro Books, pp. 96- 97.ISBN 1-5866-3097-0.

vⁱⁱ Kulkarni, GS (2009). Textbook of Orthopaedics and Trauma. India: Jaypee Brothers Medical Publication, pp. 895-898. ISBN 9350908522. ^viii Maton, Anthea; Jean Hopkins; Charles William McLaughlin; Susan Johnson; Maryanna Quon Warner; David LaHart; Jill D. Wright (1993). Human Biology and Health. Englewood Cliffs, New Jersey: Prentice Hall. ISBN 0-13-981176-1

i McNeilly, C. M.; Banes, A. J.; Benjamin, M.; Ralphs, J. R. (1996)."Tendon cells in vivo form a three dimensional network of cell processes linked by gap junctions". Journal of Anatomy 189 (Pt 3): 593-600. PMC 1167702. PMID 8982835

x Genetics Home Reference. U.S. National Library of Medicine. 2014-05-05. Retrieved 2014-05- 10.

xⁱ Ebner S, Nguyen VA, Forstner M, Wang YH, Wolfram D, Liu YJ, Romani N (April 2007).

"Thymic stromal lymphopoietin converts human epidermal Langerhans cells into antigen- presenting cells that induce proallergic T cells". J. Allergy Clin. Immunol. 119 (4): 982- 90.doi:10.1016/i.iaci.2007.01.003. PMID 17320941

xⁱⁱ Michel, Gurvan; Thierry Tonon; Delphine Scornet; J. Mark Cock; Bernard Kloareg (October 2010). "The cell wall polysaccharide metabolism of the brown alga Ectocarpus siliculosus.

Insights into the evolution of extracellular matrix polysaccharides in Eukaryotes". New

Phvtoloaist 188 (1 ): 82-97. doi:10.1111/i.1469-8137.2010.03374.x

xⁱⁱⁱ Alberts, Bruce (2002). Molecular biology of the cell. Garland Science. ISBN 0-8153-3218-1 ^xiv Raspanti, M.; Congiu, T.; Guizzardi, S. (2002). "Structural Aspects of the Extracellular Matrix of the Tendon : An Atomic Force and Scanning Electron Microscopy Study.". Archives of Histology and Cytology 65 (1 ): 37-43. doi:10.1679/aohc.65.37.PMID 12002609

"" Sharma, P. M., N., (2006). "Biology of tendon injury: healing, modeling and

remodeling". Journal of Musculoskeletal and Neuronal Interactions 6 (2): 181—

190. PMID 16849830

™ Tanne, Kazuo; Sakuda, Mamoru; Burstone, Charles J. (December 1987). "Three-dimensional finite element analysis for stress in the periodontal tissue by orthodontic forces". American Journal of Orthodontics and Dentofacial Orthopedics 92 (6): 499-505. doi: 10.1016/0889- 5406(87)90232-0

mⁿ [ (Herbert F - Wolf; Klaus H. Rateitchak(2005) Periontopathy. Thieme.pp.l2-ISBN 978-0-8657-902-0. Retried 21 June 2011)] ^xviii [Illustrated Dermal Embryology, Histology and Anatomy,Bath-Balogn and Fenhrenbach, Elsevier, 2011, page 184]

xⁱ The American Academy of Periodontology. Proceedings of the World Workshop in Clinical Periodontics. Chicago:The American Academy of Periodontology; 1989:1/23-1/24.

^ Parameter on Plaque-Induced Gingivitis". Journal of Periodontology 71 (5 SuppI): 851-2. 2000.

Research, Science and Therapy Committee of the American Academy of Periodontology (2001 ). "Treatment of Plaque-Induced Gingivitis, Chronic Periodontitis, and Other Clinical Conditions".Jouma/ of Periodontology 72 (12): 1790-1800