WO2012104663A1

WO2012104663A1 - Composition for treatment of bone and joint disorders

Info

Publication number: WO2012104663A1
Application number: PCT/HR2012/000002
Authority: WO
Inventors: Zdravko MAUKO
Original assignee: Mauko Zdravko
Priority date: 2011-02-02
Filing date: 2012-01-24
Publication date: 2012-08-09
Also published as: HRPK20110080B3; HRP20110080A2

Abstract

The composition for treatment of bone and joint disorders is composed of a mixture of dry incense resin extract, dry myrrh resin extract and dry lactoferrin extract. The synergistic efficiency of this composition is considerably better than the sum of efficiencies of its individual components. The best results of treatment of bone disorders such as arthritis and arthrosis are achieved with a composition which contains incense resin extract, myrrh resin extract and lactoferrin extract in approx. weight ratios of 2:2:1. The composition is taken orally in tablet or capsule form.

Description

COMPOSITION FOR TREATMENT OF BONE AND JOINT DISORDERS

Technical Fields

The invention relates to a composition for the treatment of bone and joint disorders, and it contains a synergistic mixture of dry incense resin extract, dry myrrh resin extract, and dry lactoferrin extract. According to the eighth edition of the International Patent Classification, the invention belongs to following areas:

A61 P 19/00 - Medical products against bone disorders,

A61 P 19/02 - Medical products against joint disorders such as arthritis, arthrosis A61 K 36/00 - Medical products of indeterminate composition containing: algae, lichens, fungi or plants or their derivatives, e.g. traditional herbal medicines.

Technical problem

Even though it is widely believed that only elderly persons suffer from bone disorders, in actuality, they affect people of all age groups. About 350 million people in the world suffer from arthritis. In most cases, people who suffer from arthritis feel pain and stiffness in the joints. Arthritis is a Greek word composed of words arthro = joint and -itis = inflammation, and marks a group of chronic illnesses which are connected with damage to joints in the body. Arthritis literally means inflammation of the joints, accompanied by the feeling of pain. There are about 200 types of arthritis, including osteoarthritis, rheumatoid arthritis and gout. The most common is osteoarthritis which relates to a degenerative joint disease as a consequence of trauma to the joints, inflammation, or the aging process. Other types of arthritis include rheumatoid arthritis, psoriatic arthritis and autoimmune forms of the disease.

There is a wide range of medical products available for treating arthritis. Medical products which are used to treat arthritis often cause serious adverse effects such as: liver damage, stomach bleeding, stomach ulcers, kidney disease and high blood pressure. Due to this, many patients resort to alternative methods of treatment, and food supplements. There are numerous food supplements on the market intended for treatment of arthritis symptoms. The most common is the combination of glucosamine sulfate and chondroitin sulfate. Although food supplements offer promising results, there are still an insufficient number of studies which prove their efficiency.

Background Art

Today there are numerous remedies on the market intended for preserving healthy joints and alleviation and treatment of arthritis. Remedies based on incense and myrrh have for a long time been traditionally used in folk medicine for the purpose of treatment of osteoarthritis and other types of arthritis. In January 2011 , in the patent data base of the European Patent Organization, Esp@cenet, there were over 20 records of patents which contain incense or myrrh in combination with other traditional medicinal herbs, and which are intended for treating arthritis. None of the aforementioned patents contain all three basic components of the composition related to the invention: incense resin extract, myrrh resin extract, and lactoferrin extract.

According to the patent W0931/13790 lactoferrin significantly inhibits the degradation of collagen caused by collagenase and shows a very good effect on the inhibition of collagenase activity.

Patent U 2009130191 points to the fact that lactoferrin inhibits the growth of osteoclasts and therefore acts therapeutically on affected bones, and acts preventively in preservation of bone health.

In January of 2007, the French company Bio Serae conducted a clinical trial of their product which was a combination of glucosamine chondroitin and lactoferrin. 57 volunteers participated in the trial. The trial results showed that the stated combination can reduce the feeling of pain for up to 50% in persons suffering from an initial stage of osteoarthritis of the knee.

Disclosure of the Invention

According to the invention, the composition for treatment of bone and joint disorders is a mixture of basic ingredients: dry incense resin extract, dry myrrh resin extract, and dry lactoferrin extract. Auxiliary ingredients are added to this mixture which necessary for producing the composition in tablet or capsule form.

Incense is an aromatic resin which is extracted from the tree of the Boswellia family. In traditional aryuvedic medicine, incense is used as an analgesic and has antiinflammatory properties. It is used for treating osteoarthritis, rheumatoid arthritis, diarrhea, pulmonary disease and wounds.

According to clinical information, the medicinal application of incense is for treatment of arthritis, bronchial asthma, Chron's disease, and ulcerative colits, and it is also mentioned in pharmacopoeia as a composition for treating rheumatism and arthritis. This is why incense is listed in the pharmacopoeia of the World Health Organization: WHO's Monograph of Selected Medicinal Herbs, Vol. 4 Geneva , World Health Organization 2009.

Contemporary science also recognizes the positive effects of incense extract in treatment of osteoarthritis of the knee. This is documented in the following papers: a) Kirnmatkar N, Thawani V, Hingorani L, Khiyani R.: Randomized, double blind study of efficiency and tolerability of the Boswellia errata extract in treating osteoarthritis of the knee. Phytomedicine 2003; 10:3-7,

b) Sontakke S, Thawani Y, Pimpalkhute P, Kabra P Babhulkar S, Hingorani H.: Open, randomized, controlled clinical study of the Boswellia serrata extract in relation to valdecoxib in osteoarthritis of the knee. Indian J Pharmacal, 2007;39:27-9.

Incense extract which contains 30% 3-0-acetil-11-keto-beta-boswellic acid, AKBA, has shown the effect of controlling the inflammatory reaction through reduction of pro-inflammatory modulators, and has also proven efficient in improving joint health due to reduction of the enzyme degradation of cartilage in patients suffering from osteoarthritis described in the following study: Sengupta K, Alluri KV, Satish AR, Mishra , Golakoti T, Sarma KV, et al.: Double blind, randomized placebo controlled study of efficiency and safety of 5-Loxin for treatment of osteoarthritis of the knee. Arthritis Res Ther 2008; 10:R85. doi: 10.1186/ar2461.

Myrrh is a type of aromatic resin which is extracted from various types of trees of the Commiphora family. In traditional medicine, myrrh is mentioned as a herb which treats symptoms of menopause, arthritic pain, diarrhea, fatigue, headache, bile and digestion disease. For this reason, myrrh is listed in the pharmacopoeia of the World Health Organization: WHO's Monograph of Selected Medicinal Herbs, Vol. 3 Geneva , World Health Organization 2007.

Myrrh has significant anti-microbial and medicinal effect in several types of diseases described in the following paper: El Ashry ES et al. Content, therapeutic value and use of myrrh. Pharmazie. 2003 Mar 58(3): 163-8.

Lactoferrin is a protein present in milk, human tears and beef. It is known to have a pharmacological effect such as an anti-bacterial effect, and a proliferation effect on lymphocytes. These effects are described in the patent document no. JP48534/1990. Lactoferrin encourages the growth of osteoblasts, improves the installation of thymidine in osteocytes and reduces apoptosis of osteoblasts for up to 50-70%. This was confirmed by a study described in the following scientific paper: L. Adlerova A. Bartoskova, M. Faldyna: Lactoferrin: review of papers, Veterinarni Medicina, 53, 2008 (9): 457-468. Apart from direct influence, lactoferrin could also affect the bone cells, preventing the activity of osteolytic cytokinins TNFa or IL-β, whose levels rise during the inflammation. Therefore lactoferrin adds to the stability of bone tissue as described in the paper: L. Adleroval, A. Bartoskova, M. Faldyna. Lactoferrin: review of papers, Veterinarni Medicina 53, 2008 (9): 457-468.

During the development stage of the composition we determined that the mixture of incense resin, myrrh resin and lactoferrin displays unique synergistic effects which reduce inflammation and pain in the joints, i.e. help with symptoms caused by arthritis and provides prevention.

The composition prepared from dry incense resin extract, dry myrrh resin extract, and dry lactoferrin extract was tested on a group of nine volunteers with diagnosed osteoarthritis of the knee. At the beginning of the trial, all subjects had symptoms of inflamed and swollen joints, pain in the knee, and reduced mobility of the knee joint. During the trial, they would each take one capsule of the composition per day in the morning before a meal, and one capsule in the evening before a meal. Each capsule contained a mixture of 140 mg of dry incense resin extract, 140 mg of dry myrrh resin extract and 70 mg of dry lactoferrin extract. In 7 days, a significant reduction of inflammation, swelling, and pain in the joints was recorded in 89 % of the subjects. Also, with prolonged application of the composition, subjects experienced great improvement of knee flexibility in about 60 days.

The stated clinical results received by application of the composition from dry incense resin extract, dry myrrh resin extract and dry lactoferrin extract, are significantly better than the usual sum of results given by individual components of this composition. These results indicate that the dry incense resin extract, dry myrrh resin extract and dry lactoferrin extract, have a synergistic effect which has until now been unknown and undocumented.

Published clinical studies show that incense resin extracts, whether individually, or in combination with glucosamine and chondroitin, yield significantly weaker results during the first seven days of application. Also, the combination of lactoferrin, glucosamine and chondroitin, yields significantly weaker results, and it requires a considerably longer period of application, and larger individual component doses for the results to manifest. The weakest results are yielded by remedies based on glucosamine and/or chondoritine and/or collagen. These remedies require a very long period of application and significantly larger daily doses in order to manifest a very weak improvement of osteoarthritis symptoms.

Therefore we can conclude that the mixture of dry incense resin extract, dry myrrh resin extract and dry lactoferrin extract represents a significant improvement and novelty in relation to the existing remedies intended for reducing inflammation and pain in the joints, and preservation of bone and joint health in arthritis.

Composition production protocol

Incense and myrrh resins are collected from their respective trees. Dry extracts of incense and myrrh are prepared in a way that a weight portion of the resin is dispersed in 5 weight portions of 70 % ethyl alcohol. The resulting suspension is macerated for 7 days at room temperature, and filtered in order to obtain a clear solution. The alcoholic solution is evaporated under pressure lower than 100 mbar and temperature lower than 40 C° until we receive a dry extract. Depending on available technology, manufacturers of the extract can also use other solvents like liquefied carbon dioxide, ether, methanol, and various acids and alkali.

Lactoferrin is isolated from cow's milk or whey, using the method where milk or whey is passed through a column with a filler which has a specific affinity for lactoferrin. Lactoferrin remains bound on the filler, and is later rinsed from the column with the help of a suitable solvent. The solvent is removed and evaporated under pressure lower than 100 mbar and temperature lower than 40 C° until we receive a dry extract of lactoferrin. Depending on available technology, manufacturers can use various fillers for columns, and various solvents for rinsing the substance from the column. It is also possible to produce human-identical lactoferrin by using microorganisms which are engineered to be capable of lactoferrin biosynthesis by using recombinant genetic technology.

The basic components of the composition, dry incense resin extract, dry myrrh resin extract and dry lactoferrin extract are mixed in approx. weight ratio of 2:2:1. Auxiliary ingredients necessary for production of tablets or capsules are added to the mixture: maltodextrin, talcum, magnesium stearate, talcum and silicon dioxide. Before placement in tablet or capsule form, the mixture of basic and auxiliary components is homogenized with a regranulator in order to get a size which is suitable for placement in tablet or pill form. Best results are achieved with the composition in doses for oral application, produced in the form of tablets or capsules, using the following weigh ratios of basic and auxiliary components: Single dose content

Component in mg

+/- 10%

Dry incense resin extract 140,00

Dry myrrh resin extract 140,00

Dry lactoferrin extract 70,00

Maltodextrine 12,70

Talcum 20,00

Magnesium stearate 10,00

Silicon dioxide 0,65

Total content 393,35

Acceptable mass deviation of certain components within one tablet or capsule equals +/- 10%.

Description of application

The composition in tablets or capsules is administered orally. The recommended dose is two tablets or two capsules per day, where one tablet or one capsule is taken before a meal in the morning and evening.

Claims

1. The composition for treatment of bone and joint disorders, characterized by consisting of a mixture of dry incense resin extract, dry myrrh resin extract and dry lactoferrin extract.

2. The composition for treatment of bone and joint disorders, characterized by the fact that one dose of the composition in tablet or capsule form contains the following content and weight proportions:

3. The composition for treatment of bone and joint disorders according to claims 1 and 2, characterized by application for treatment of bone and joint disorders such as arthritis and arthrosis.

4. The composition for treatment of bone and joint disorders according to claims 1 to 3, characterized by oral application in doses amounting to two tablets or two capsules per day, where one capsule or tablet is taken in the morning, and one in the evening, before a meal.