WO2020142018A1

WO2020142018A1 - Use of vitamin d for treatment of arthrosis (osteoarthritis)

Info

Publication number: WO2020142018A1
Application number: PCT/TR2019/050008
Authority: WO
Inventors: Huseyin Coban
Original assignee: Huseyin Coban
Priority date: 2019-01-06
Filing date: 2019-01-06
Publication date: 2020-07-09
Also published as: DE112019006563T5

Abstract

The present invention relates to use of vitamin D or a pharmaceutically acceptable metabolite, precursor, derivative or analogue thereof in the preparation of a medicament for the treatment of arthrosis(osteoarthritis). It is a treatment method with vitamin D injection into the arthrosis joint.

Description

VITAMIN D USE AS INTRAARTICULAR INJECTION IN TREATMENT OF ARTHROSIS

(OSTEOARTHRITIS).

Technical Field

The present invention relates to the use of vitamin D for the treatment of arthrosis by the intraarticular injection method. The vitamin D compound can be administered in therapeutically effective doses to treat arthrosis, using intermittent administration to avoid any side effects.

Background of Invention

The human body has not adapted to the life of urbanization. Skin exposure to sunlight has been decreased in time. This causes vitamin D deficiency. The rate of vitamin D deficiency in our population is over 80%. Most patients with arthrosis suffer from vitamin D deficiency. Vitamin D is a very important for human metobolism. Vitamin D is used in the treatment of osteomalacia, osteoporosis and osteopenia. Oral or intramuscular forms are available. Pharmacologically, phase 4 studies are available.

The osteo-arthrosis is the most frequent articular disease worldwide, the majority of all people in the age above sixty-five is affected thereof. Inevitably, from it results a very high clinical, health-political and economical relevance. In the course of said articular disease, which is primarily degenerative age-related, arise a step-wise focal destruction of the joint surface and a reactive mal-regulated regional growth of the adjacent and sub-chondral bone structures (osteophytes). The results are pains and limited function and motility of the affected joint. Systemic factors, which influence the genesis of an osteo-arthrosis, are the age, the gender, weight, acute osteoporosis, a familial preload and mechanical overload. Local factors are the specific joint form, mal-positions, traumas, as well as bio-mechanic factors, which affect the joint. Despite the underlying degenerative genesis, also in the osteo-arthrosis inflammable changes arise like a synovitis (inflammation of the inner joint skin), as well as a production of inflammation promotional biological messengers, for example of cytokines and growth factors (Rubin, J. Am. Osteopath. Assoc., 101 , 2001 , p. 2-5; van der Kraan and van den Berg, Curr. Opin. Nut. Metab. Care, 3, 2000, p. 205-21 1 ). No medical cure exists for arthrosis. The progressive degeneration of the joint due to osteoarthritis is irreversible. Present therapies are directed to palliative medical therapies to reduce inflammation and pain and surgical therapies to reconstruct an affected joint or, in severe cases, to replace the joint with an artificial, prosthetic joint.

Presently available medications for the treatment of osteoarthritis include anti-inflammatory compounds such as corticosteroids, and non-steroidal anti-inflammatory drugs such as aspirin, phenylbutazone, and ibuprofen, and pain relievers such as acetaminophen. Medical treatment, other than that directed against the cause of the osteoarthritis, such as antibiotics in the case of infectious osteoarthritis, generally does not alter the progression of the disease or reverse the pathologic changes in the joint.

In recent years, medical treatments for osteoarthritis have been proposed to replace some of the natural constituents of synovial fluid and cartilage which are decreased in the arthrosis joint. These constituents include glucosamine or polymers thereof, including hyaluronic acid, chondroitin sulfate, and glycosaminoglycans. Nutritional compounds such as the omega-3- fatty acids have been suggested to have anti-inflammatory properties which may be effective in reducing symptoms of osteoarthritis. An injectable composition containing polysulphated glycosaminoglycan has been reported to be effective in treating the symptoms of osteoarthritis. Little if any success has been reported in treatment of osteoarthritis, however, with glucosamine or omega-3-fatty acids.

Object of the Invention

Object of the invention provide an effective palliative medication for the treatment of osteoarthritis which is both safe and effective when used for both short-term and long-term therapy.

In a preferred application of the invention, vitamin D or a pharmaceutically acceptable metabolite, precursor, derivative or analogue thereof is used in the preparation of a medicament for the treatment of arthrosis. All vitamin D forms, molecules, derivatives, mixtures with other substances, other substances and compounds of the invention are in the art suitable for the treatment of arthrosis.

In a preferred application, administration of the medicament is for intra-articular administration. Vitamin D is injected into the joint prevents pain by blockade the pain receptors. Vitamin D prevents cartilage destruction. Strengthens cartilage. Vitamin D is a fat-soluble vitamin. Its structure provides lubrication and prevents friction in the joint. Vitamin D inhibits the formation of osteophytes. Stops the growth of existing osteophytes. In a preferred application, the medicament is in unit dose form and the effective amount of vitamin D is between 30000-600000 IU.

In a preferred application, the medicament for a particular treatment for a selected patient having serum vitamin D levels are between 30-100 ng/ml_. Vitamin D is difficult to achieve toxic doses. Vitamin D toxicity, also called hypervitaminosis D, is a rare but potentially serious condition that occurs when you have excessive amounts of vitamin D in the body. A 34-year old female patient, had an overdose of Vitamin D. Three days apart, he used 1 1 ampl 300000 units of Vitamin D. The serum vitamin D level was 150 ng/ml_. At these levels, the patient did not have any clinical problems. After four months, the serum level decreased to 36 ng/ml_. Very high doses are required to reach toxic doses. This patient may also have a vitamin D absorption problem. It is not currently possible to detect this. However, most effective treatment has been achieved when serum vitamin D levels are between 30-100 ng/ml_. This should be considered when injecting. Serum vitamin D, phosphate, Ca, creatine and Parathormone levels should be considered before use of Vitamin D. Ca and urine Ca values should be considered. Care should be taken to not to increase the serum vitamin D level above 100 ng/ml_.

In a preferred application, the vitamin D is subsequently administered at least 14 days later for a selected patient having serum vitamin D levels are below 100 ng / ml_.

In a preferred application the vitamin D is administration is repeated at an interval of 3-12 months for a selected patient having serum vitamin D levels are below 100 ng / ml_.

In a preferred application, the Vitamin D is in combination with a joint lubricant selected from the group consisting of hyaluronic acid, sodium chlorite, disodium phosphate, potassium hydrogen phosphate, sodium chloride, sodium hydrogen phosphate dihydrate, dibasic sodium phoshpate dodecahydrate, peptides, phosphate buffered salt, sodium monohydrogen phosphate, sodium hydrogen phosphate, sodium succinate, mannitol, chondritein sulfate.

In a preferred application said vitamin D is vitamin D3 (cholecalciferol), vitamin D2 (ergocalciferol), calcifediol, alfacalcidol or calcitriol, or a combination thereof, or a metabolite, precursor, derivative or analogue thereof. Vitamins D2 and D3 vitamin are the most common in daily life. Vitamin D2 is also called Ergocalciferol. It is produced by yeasts and mostly taken by humans with plant consumption. Vitamin D3 is also called cholecalciferol and is produced in the skin with sun exposure. It is also found in foods of animal origin.

Detailed Description of Invention In order to achieve the aforementioned objects, the present invention discloses use of Vitamin D for treatment of arthrosis.

In Example 1 , Vitamin D levels of below 30 ng/mL was administrated at 600000 units by intra- articular administration. Two weeks later, serum vitamin D levels was repeated as 300000 units. Each insert was applied as 50000 units. This method is selected especially in patients with rheumatic disorders in many joints. Vitamin D levels 30-70 ng / ml. can be made up to 300000-600000 units. If necessary, two weeks later, the serum levels of 300000 units can be repeated.

In Example 2, Vitamin D level, 70-1 OOng / ml. 300000 units was administered to the patient medicament by intra-articular administration. Repeated after two weeks according to serum values by dose adjustment. This group of patients should be more careful.

Intra-articular administration repeated at intervals of 3-12 months. Blood serum levels was checked before each application. If serum vitamin D levels are above 100 ng / ml_, it is appropriate not to inject Vitamin D to the patient.

In a low percentage, the first day side effect was feeling of pain, swelling and fullness. Vitamin D is combined with analgesic-antiinflammatory for the first day administration.

If there is osteochondritis dissecans or meniscus complex rupture in the joint, this pathology should be treated first. Then, vitamin D injections should be performed.

The maintenance of the physical stability of a pharmaceutical product can be ensured if no change occurs in the physical structure of that product. Therefore, whether the physical stability is maintained or not is assessed by determining changes in various physical properties of the product during formulation development process. Properties such as the color, scent, taste, pH, clarity, viscosity, homogeneity, density which are among the physical properties of a pharmaceutical are the basic physical properties playing role in the assessment of the physical stability thereof.

Claims

1 . Use of vitamin D or a pharmaceutically acceptable metabolite, precursor, derivative or analogue thereof in the preparation of a medicament for the treatment of arthrosis.

2. A use according to claim 1 wherein administration of the medicament is for intra- articular injection administration.

3. A use according to any one of the preceding claims wherein the medicament is in unit dose form and the effective amount of vitamin D is between 50000-600000 IU.

4. A use according to any one of the preceding claims wherein the medicament is for a particular treatment for a selected patient having serum vitamin D levels between 0-100 ng/mL.

5. The patient with serum vitamin D level 0-100 ng / mL is injected with arthrosis.

6. A use according to claim 5, wherein the vitamin D is subsequently administered at least 14 days later.

7. A use according to claim 6, wherein the vitamin D is administration is repeated at an interval of 3-12 months for a selected patient having serum vitamin D levels are below 100 ng

/ mL.

8. A use according to any one of the preceding claims wherein the vitamin D is in combination with a joint lubricant selected from the group consisting of hyaluronic acid, sodium chlorite, disodium phosphate, potassium hydrogen phosphate, sodium chloride, sodium hydrogen phosphate dihydrate, dibasic sodium phoshpate dodecahydrate, peptides, phosphate buffered salt, sodium monohydrogen phosphate, sodium hydrogen phosphate, sodium succinate, mannitol, chondritein sulfate.

9. A use according to any one of the preceding claims wherein said vitamin D is vitamin D3 (cholecalciferol), vitamin D2 (ergocalciferol), calcifediol, alfacalcidol or calcitriol, or a combination thereof, or a metabolite, precursor, derivative or analogue thereof.