HK1116421A - Anti-inflammatory extract and agent and method for the production thereof - Google Patents

Description

Anti-inflammatory extract, pharmaceutical preparation and method for producing the same

Technical Field

The present invention relates to biologically active agents derived from plant raw materials and useful for the complex treatment of different inflammatory diseases and as agents for increasing the non-specific resistance of organisms.

Prior Art

Modern anti-inflammatory agents are represented by two main classes, namely steroidal and non-steroidal pharmaceutical preparations.

The mechanism of action of steroid agents (glucocorticoids) involves inhibition of phospholipase a2, preventing the formation of eicosanoids (prostaglandins and leukotrienes), the major tissue regulators and mediators in inflammatory processes.

The effect of non-steroidal agents involves the inhibition of cyclooxygenase activity, which results in a reduction in the formation of prostaglandins and thromboxanes and thus in a reduction in inflammation.

Although either formulation has significant anti-inflammatory activity, there are still many limitations to their long-term use due to adverse side effects, the most serious of which are gastrointestinal damage, i.e. nausea, vomiting, gastric ulceration.

In addition, these preparations can cause liver and kidney dysfunction and bleeding, leukopenia to the extent of agranulocytosis, anemia. It also can cause central nervous system changes, such as vertigo, headache, excitement, insomnia, fatigue, and edema. All of these factors limit the use of steroidal and non-steroidal formulations in practical drugs and there is still a need to develop new low-toxicity anti-inflammatory formulations. Preparations of natural origin can meet most of these needs.

In folk medicine, plant extracts in the form of infusion solutions, tinctures, compresses and alcohol creams are used to treat joint pain of any cause. For this purpose, wild rosemary, bourtree, sweet clover, oregano, nettle, burdock, juniper, chrysanthemum, thatch, pine, violet, equisetum arvense, hop, thyme, bur-marigold, eucalyptus, ginger or birch bud are used. Based on these and other herbs, several biologically active food additives have been developed, such as Antiartrol, Bambuflex, Dokholodan (di o х a zhao), Epam-31, burdock root, Art, Joint Flex, and others (see Federal register of biological active food additives, Moscow, 2000, Chapter 10). They are all suggested as anti-inflammatory and tonic agents regulating processes in the bone and cartilage tissues of arthrosis.

The anti-inflammatory agents of natural origin that are currently being demonstrated are Aescusan, Romasulan, Tycveol, Calendal, Traumel, and the like. However, there is still a need to develop anti-inflammatory agents for the treatment of arthropathy.

In the traditional indian drug "ayurveda", the resin of Boswellia santa (Boswellia serrata) has been used for a long time as an anti-inflammatory agent for the treatment of arthritis, osteoarthritis, inflammatory diseases of the lungs and intestines. The main active ingredient of the resin is boswellin (boswellian) acid. Studies of the alcohol and chloroform extracts of this resin and of the individual boswellian acids have shown that under their action the content of anti-inflammatory mediators is significantly reduced (mainly due to inhibition of lipoxygenase, which prevents the inflammatory process [ Sharma M.L., Bani S., Singh G.B., 1989, Inimmunopharmacol 11 (6): 647-652 ]).

Along with anti-inflammatory effects, Sharma m.l. and several other authors have disclosed the analgesic, antipyretic, immunomodulatory, antibacterial, hepatoprotective, and antihyperlipidemic effects of boswellianacid.

The use of tetrahydropiperine and its analogs as anti-inflammatory agents in anti-tumor compositions containing curminoids is known. The composition may also contain turmeric extract, mastic and other plant components (US 2002/0058695, published 2004).

Food additives containing an extract of pepper fruits as an essential component of the composition are known. It is also noted that the pepper fruit extract can be used as an adjuvant for the absorption of substances such as boswellin or boswellia alcoholic extract, curcuminoids or alcoholic extract of turmeric, pine bioflavonoids, vitamins E and C. The additive is provided in the form of capsules (US 5,536,605, published in 1996).

Dietary supplements are known to have anti-inflammatory, analgesic, protective and antioxidant properties. The additive contains resveratrol stilbenene glycosides from different plant families, turmeric extract and furthermore boswellia extract. No data were obtained on the use of oil extracts of the above plants (published in PCT application WO 0195727, 2001).

Compositions based on boswellia extracts or boswellian acids or their derivatives in an aromatic carrier like lemon oil or peppermint oil, suitable for use in the oral cavity, are known. Another possible use of the composition for administration with additional anti-bacterial or anti-inflammatory agents or vitamins is also mentioned. However, turmeric and pine extracts have not been mentioned (PCT application WO 0062751).

Since the mechanism of action of boswellian acid has been recognized to be primarily through inhibition of lipoxygenase, which prevents inflammatory tissue regulator formation, this has been confirmed by previous studies and it is believed that prostaglandin and free radical processes play a more important role in the inflammatory mechanism, while complexing agents are produced by additionally including other bioactive substances that provide more significant anti-inflammatory and tonic effects, in order to increase the positive effects of the treatment.

Disclosure of Invention

The aim of the present invention is to provide a drug with a broad pharmacological spectrum, so as to be able to combine the treatment of inflammatory diseases of different etiologies and to increase the protective function of the organism.

The invention provides an anti-inflammation extract, which contains dry frankincense extract or derivatives thereof contained in a vegetable oil carrier according to the following component ratio:

dried Boswellia carterii extract or its derivatives up to 40g

Vegetable oil carrier up to 100 ml.

Another aspect of the present invention is an anti-inflammatory agent comprising a dried boswellia extract contained in a vegetable oil extract produced from siberian lycopodium seeds and turmeric roots in the following compositional ratio:

dried Olibanum extract 5-40g

Oil extracts of the seeds of Pinus sibirica and Curcuma rhizome were up to 100 ml.

The medicament is provided in the form of a soft gelatin capsule.

The method for the production of anti-inflammatory agent comprises soaking whole Pinus sibirica seeds in water-alcohol solution, followed by mixing said seeds with vegetable oil extract in a volume ratio not exceeding 1: 20, thereby obtaining Pinus sibirica seed oil extract, pre-grinding Curcuma rhizome roots and sieving, mixing said roots with Pinus sibirica seed oil extract in a volume ratio not exceeding 1: 10 and extracting to obtain Pinus sibirica seed and Curcuma rhizome oil extract, adding dried Olibanum extract in an amount of 5-40g/100ml oil extract and keeping said mixture until the desired product is completely dissolved.

The extraction of the components is carried out by a rotary-pulsating process at a temperature not exceeding 50 ℃, followed by standing and filtration of the oil extract.

Another aspect of the present invention is an anti-inflammatory agent comprising gelatin capsules containing lecithin, butylated hydroxytoluene, alpha-tocopherol acetate, ascorbyl palmitate, dried boswellia extract in siberian lycopodium seed and turmeric root oil extract in the following mg/capsule ratio:

dried Olibanum extract 25-35

250-280 extract of pinus sibirica seed and turmeric root oil

0.30-0.35 of alpha-tocopherol acetate

Ascorbyl palmitate 0.75-0.85

Lecithin 0.15-0.25

0.01-0.02 parts of butyl hydroxy toluene.

The above agents can be used as biologically active additives.

Preferred embodiments of the invention

The above extract has significant anti-inflammatory activity and at the same time supports an increase in organism non-specific resistance.

The anti-inflammatory extract is obtained by dissolving dried Boswellia serrata extract in an oil carrier, particularly corn, soybean, sunflower, or other oils, in a volume ratio of (2-40) to 100 dry extract to oil carrier. The study of the properties of the extracts was performed using Boswellik, a dry extract of Boswellia carterii dissolved in corn oil.

Diclofenac was used to compare the therapeutic activity of Boswellik. The study was conducted on mice that are indistinguishable between males and females following oral administration of the formulation.

The extract is studied for anti-exudation and analgesic effectAnd ulcerogenic effects, showed that Boswellik has therapeutic activity, similar to diclofenac. The most significant anti-inflammatory properties of Boswellik were at 100 and 130mg/kg (IC of 1/20)₅₀) At the optimum dose of (a). In contrast to diclofenac, Boswellik showed no irritating effect on the gastrointestinal tract and a tolerance index (ratio of toxicity to ulcerogenic dose) 371 times higher. In contrast to diclofenac, Boswellik is safe during long-term administration because the safety index, which is the ratio of ulcerogenic/efficacy, is 0 for the first and 4.3-9.9 for the second.

Anti-inflammatory Activity Studies by Boswellik on the Effect of the acute exudative inflammation (peritonitis) model in rats and mice

Evaluation of Boswellik anti-inflammatory activity was performed in an acute inflammatory process-peritonitis-rat and mouse model, which was induced by intraperitoneal injection of acetic acid. Boswellik demonstrated the most significant anti-exudation effect at 100 and 130mg/kg doses.

The effect of diclofenac at the 8mg/kg dose and Boswellik at the 10, 30 and 260 doses on the inflammatory exudative volume in the abdominal cavity of animals was significantly weaker. An effective dose of Boswellik-130 mg/kg-has been determined based on the results obtained.

Data relating to the evaluation of Boswellik anti-exudation are presented in tables 1 and 2.

Evaluation of the anti-exudative Effect of Boswellik in the rat peritonitis model

Experimental group of animals n-10	Volume of peritoneal exudate,. mu.l	Degree of anti-exudation A ═ Ro-Rk]Rk100％
			Control group	4440±310	0
Diclofenac acid 8mg/kg	3350±220*	24
			Boswellik 10mg/kg	4100±150	8
Boswellik 30mg/kg	3770±140	15
			Boswellik 100mg/kg	2780±150*	37
Boswellik 130mg/kg	2270±250*	49
			Boswellik 260mg/kg	2980±360*	33

Note: significant difference from the control group p < 0.05

Evaluation of anti-exudative Effect of Boswellik in mouse peritonitis model

Experimental group of animals n-10	Volume of peritoneal exudate,. mu.l	Degree of anti-exudation A ═ Ro-Rk]Rk100％
			Control group	240±10	0
Diclofenac acid 8mg/kg	37±2*	85
			Boswellik 30mg/kg	45±4	81
Boswellik 130mg/kg	29±2*	88
			Boswellik 260mg/kg	147±6*	39

Note: significant difference from the control group p < 0.05

Furthermore, in vitro experiments on isolated human blood cells have revealed specific immunomodulatory effects of the investigated preparations (Boswellik and diclofenac) on immunoglobulin synthesis.

Boswellik oil solutions at a dose of 260. mu.g/ml increased spontaneous and activated synthesis of IgG. Doses of 10-30 μ g/ml may also increase spontaneous and activated synthesis of IgA. It had no effect on the synthesis of IgM, IgG1 and IgG 4.

The anti-inflammatory effect of boswellic acid is due to inhibition of 5-lipoxygenase (5-LOG) activity and reduction of leukotriene synthesis. Literature data demonstrates that the effect of Boswellik on immunoglobulin synthesis can also be a result of boswellic acid on 5-lipoxygenase (5-LOG) activity and leukotriene synthesis.

The effect of Boswellik on immunoglobulin synthesis can occur both by directly affecting the B-lymphocytes producing them and indirectly, by acting on macrophages, since leukotrienes and 5-LOG play an important role in the physiology of B-lymphocytes and macrophages.

The anti-inflammatory agent of the present invention can also be used to increase non-specific resistance of an organism and increase the protective function of an organism as a biologically active food additive.

The composition of the agent of the present invention is developed based on analysis of pharmacological effects of its components and long-term self-experience with respect to the creation of agents of natural origin. The quantitative ratios of the components were empirically obtained and confirmed by experimental studies on animals.

As can be seen from the composition of the inventive medicament, the formulation uses a relatively high content of the siberian lycopodium seed and turmeric oil extract in addition to the boswellia dry extract. The selection of seeds of siberian pine trees is made on the basis of their long-term experience in folk medicine, their high biological activity and also on the basis of their experience in the pharmaceutical compositions we have developed, which are widely used in actual medicine.

The medicinal properties of the seeds of pinus sibirica are known to originate from the XI th century: even Avicenna suggests that they be administered with honey for the treatment of stones and ulcers. Broth and alcohol tincture of the shell of the seed of Pinus sylvestris in Russia are used for the treatment of rheumatism, gout and arthritis, and infusion solutions are used for the treatment of neurosis, renal and hepatic diseases and haemorrhoid. High-calorie emulsions and "plant creams" are prepared from seed (nut) kernels and are useful in the treatment of tuberculosis, kidney disease, bladder disorders, and as a combined tonic.

Studies of the chemical composition of the stone pine seeds revealed: the broad composition of the biologically active substance is a protein containing 14 amino acids, 70% of which are essential, vitamin A, E, B1, fatty acids, fatty oils, and trace elements (Mg, Mn, Fe, Co, Cu, J, P). No other known plant material has such a group of active substances. We have used Kedrol, an extract of Centipeda palustris oil using corn oil as a component of the medicament of the present invention. The pharmacological effects of the extract include enhancing smoothness, anti-oxidant, bactericidal, wound healing and other useful properties, which enhance the anti-inflammatory effects of boswellic acid.

The composition further comprises turmeric (turmeric), a perennial plant of the family Zingiberaceae. The major biologically active substance of turmeric is curcumin, which is located most predominantly in its roots and rhizomes. The anti-inflammatory activity of curcumin and its derivatives is due to the presence of hydroxyl and phenolic groups in the molecule, which are involved in the inhibition of lipoxygenase. In addition to the direct effect of curcumin on the mechanism of the present invention of inflammation, a number of other positive pharmacological properties have been identified in animal experiments: it protects the animal liver under different hepatotoxic effects. The liver protection effect of curcumin is due to its antioxidant properties, which can increase the protective function of the organism. Stress-induced gastric ulcer is known to be inhibited by curcumin. Evidence suggests that turmeric extract has anti-cancer, hypocholesterolemic, anti-hypertensive, antibacterial, and antiviral activity, which is a perfect complement to its anti-inflammatory effects. Turmeric oil extract is considered to be one of the most promising sources for increasing organism non-specific resistance.

Therefore, the agent of the present invention comprises a compound having potent anti-inflammatory and combined tonic effects.

The agent of the present invention is produced as follows.

The technology for producing oil extracts comprises the following basic steps:

-vegetable oil extraction of whole Siberian Stone Pine (SSP) seeds (after preliminary seed soaking with 50% ethanol) using a rotary-pulse technique at an SSP: vegetable oil ratio not exceeding 1: 20 for at least 20 minutes;

-extracting the primarily ground and sieved turmeric root with SSP oil extract at a ratio of turmeric root to SSP extract of not more than 1: 10, while stirring (300rpm) and heating up to 40 ℃, for 1.5-2 hours;

dissolving the dried boswellia extract (with boswellic acid content of at least 80%) in the SSP and turmeric oil extracts at room temperature and keeping the mixture for 12 hours (until complete dissolution). The following parameters of the oil extract were studied: visual appearance (clarity), thermal stability (level of peroxide number-ALL-UNION STATESTANN.26593) and characteristics of important groups of actives.

For analysis of individual boswellic acids, flavonoids and diterpenes, a reversed phase liquid chromatography method was used. The detection wavelength of boswellic acid is 254 nm. The UV-detection wavelengths of diterpenes and flavonoids (in SSP oil extract) were 254 and 289nm, respectively. The calculation of curtuminoid relative to total curcumin content was performed by direct spectrophotometry at a wavelength of 425nm using curcumin standard samples.

In animal experiments, experimental studies of the agents of the invention were conducted to reveal the presence of specific pharmacological activity.

Study of anti-inflammatory Activity in Chondrus crispus-induced paw edema model in rats

Experiments were performed on rats (180-200g) with male indistinguishability. Each experimental group included 10 individuals. The inflammatory response (edema) was initiated by administering 0.1ml of 1% carrageenan solution to the supbplantar. All substances to be studied were administered orally in a volume of 0.3ml (the agents were provided in several doses) according to the following dosing schedule: inflammation was preceded by once daily for 2 days, day 3, and 4 hours prior to carrageenan administration. The evaluation was performed after 3, 12 and 24 hours. Phenylbutazone and diclofenac were used as control formulations, which are non-steroidal anti-inflammatory formulations with analgesic and antipyretic activity. The formulations were orally administered to animals as a suspension in starch mucilage at the following doses: phenylbutazone-56 mg/kg and diclofenac-8 mg/kg.

The evaluation of the effect of the substances studied included anti-inflammatory, analgesic and antipyretic activity. The overall index of inflammatory process activity is assessed by standardized biochemical and hematological methods: ESR, sialic acid, fibrinogen levels and leukocyte content were determined. The antipyretic effect of the formulations was assessed by their ability to lower the skin temperature of rat paw at the site of the inflammatory lesion.

The results of the study carried out show that all doses of the agent of the invention show anti-inflammatory properties. The activity was found to be more pronounced at the 250mg/kg dose, thereby maintaining a positive effect, and exceeding the effect of the phenylbutazone and diclofenac to some extent.

Evaluation of anti-inflammatory Activity in formalin-induced arthritis rat model

The arthritis model in animals was induced by injecting 0.1ml of 2% formalin solution into the knee joint cavity. After 24 hours, an acute arthritis model was obtained, which is suitable for studying the anti-inflammatory and anesthetic effects of the formulation. Phenylbutazone and diclofenac were again used as control formulations. The agents of the invention (3 doses) were dissolved in corn oil and administered according to the following schedule: intraperitoneally (using a probe) daily for 3 days prior to inflammation and 4 hours prior to formalin injection on day four. The study formulation was administered once daily for a total of 7 days. Evaluation of treatment outcome was performed on day 4 and day 8. Anti-inflammatory activity was assessed using parameters of volume, pain sensitivity and limb inflammation temperature. The total activity index (total percentage of 7-day reduction in size of affected extremities) and the therapeutic index (ratio of total activity index of the formulation to total activity index of the formalin group) were calculated.

The agent of the invention surpasses the effects of phenylbutazone at all doses and is practically no worse than diclofenac at 250mg/kg doses in terms of anesthetic and antipyretic activity.

In the formalin arthritis model, the talus calf joint and gastric mucosa of rats were also studied. The histological section includes a joint region with adjacent portions of bone tissue surrounding soft tissue, which is intimately connected to the joint including the adjacent skin, and a series of observations of the epidermis are made.

During visual examination of the joints in control rats (formalin-induced arthritis, no treatment), enlargement of the joints and smoothing of their contours were observed. At the incision, the periarticular tissue is edematous. A small amount of entrained liquid is present in the joint cavity. In the microscopic examination of the knee joint, the periarticular tissue hemorrhages and edema, as well as changes in the synovium were observed, and in the fibers thereof, the fibrocellulite was observed hemorrhages, edema, and lymphatic infiltration.

The rat joints treated with the agent of the present invention did not show any significant visual changes. Histologically, the synovium, which lines the surface of the joint, contains few differentiated connective tissue cells with rounded or oval nuclei. No congestion and lymphatic infiltration were observed.

During the dissection of the experimental rats, the size and shape of the stomach and intestine showed no change. The gastric mucosa is bright, smooth and light pink. The lumen of the small intestine is uniform throughout its length. The small intestinal mucosa is bright, smooth and light pink.

During histological studies of the stomach and small intestine, no destructive or inflammatory changes of the mucosa were noted. The epithelium of the small intestinal mucosa did not show any change.

Study of anti-inflammatory Activity in formalin-induced arthritis Rabbit model

The experiment was performed on a 51 rabbit "Chinchilla" having a weight of 2800-. Animals were divided into 3 groups: first group-control animals (formalin arthritis), second group-diclofenac at a dose of 8mg/kg, and third group-the agent of the invention at a dose of 250mg/kg for the experimental formalin arthritis studied. The arthritis model was induced by administering 0.1ml of 2% formalin solution into the knee joint cavity and an acute arthritis model was obtained after 24 hours.

The agents studied and diclofenac were administered according to the following protocol: for prophylactic purposes, intragastric administration via the probe was once daily on day 4 prior to arthritis stimulation and 4 hours prior to formalin administration on day 4. The treatment is carried out for 7 days by once daily administration of the agent of the invention and diclofenac.

Animals were euthanized under cyclohexbarbital anesthesia 3, 7, and 14 days after arthritis induction. Blood was collected from the auricular vein before the start of the experiment and before euthanasia and used to determine hematological parameters.

For histopathological studies, the joints and surrounding tissues were extracted and fixed in 10% neutral formalin.

The use of diclofenac greatly reduced the number of erythrocytes and hemoglobin in the peripheral blood compared to the initial levels during all observation periods. In general, the use of the agents of the invention does not have any significant effect on the content of erythrocytes and hemoglobin. The hematocrit, which reflects the volume ratio of the formed component to plasma, decreases under the effect of diclofenac throughout the observation period, particularly on days 3 and 7, without the inventive agent affecting this parameter. The mean hemoglobin content of red blood cells is a derived index, which reflects the state of the blood system. During the administration of diclofenac, the parameters decreased, but during the application of our agent, the parameters did not change. Thus, during the induction of formalin arthritis, a clear trend towards an anemic state was observed due to the treatment with diclofenac, whereas no significant effect on the erythrocyte parameters was observed when treated with the agent of the invention. A decrease in platelet levels over the duration of the study was observed with diclofenac, and this decrease was not observed when our agent was used. Under the action of our agent and diclofenac, there was no significant decrease in leukocyte number, no change in monocyte number, and an increase in granulocyte number throughout the observation period. Thus, the administration of diclofenac has a significant effect on peripheral blood parameters, in particular on the number of erythrocytes. No negative response was observed to both white blood cells and red blood cells under the action of our agent.

According to the results of histological studies of joints, inflammatory and destructive changes under the action of diclofenac are observed, thereby generally affecting the surface area of the articular cartilage. Inflammatory responses are also found in joint capsule tissues. The blood vessels in this area dilate and engorge with blood. 7 days after diclofenac administration, the articular surface had an uneven contour and affected the surface area of the articular cartilage. The surface of the articular cartilage was flattened 14 days after administration of diclofenac, while irregularities were observed only in individual animals, most notably in the peripheral part of the articular surface.

When treated with the agent of the invention 3 days after the start of the experiment, destructive changes were observed in the cartilage of the articular surface, which is however superficial and usually the outer region of the articular cartilage is affected. 7 days after the start of the experiment, the destructive changes of articular cartilage were reduced in the group of animals given our agent. Only in some cases, in a small part of the cartilage surface close to the joint capsule, minor changes in irregular form are observed. The state of the articular cartilage was completely standardized after 14 days of administration of our agent. The surface of the articular cartilage is flat, smooth and free of visible deformities (defects) and defects. Thus, during the administration of diclofenac, the inflammatory process subsequently subsides in most animals within 14 days. After 7 days during the administration of the agent of the present invention, the destructive changes of the articular cartilage and the surrounding tissues were reduced.

Generally, according to data from hematological, biochemical and pathomorphological studies, the agents of the present invention have significant anti-inflammatory, analgesic and antipyretic activities compared to the effects of diclofenac and phenylbutazone, but, unlike the latter, have no adverse side effects on parameters of peripheral blood and the state of articular cartilage.

Investigation of other Properties of the inventive Agents

Experimental studies carried out on general toxicity (acute, subacute, chronic and local irritant effects), allergenicity and effects on the immune system have shown that the formulations of the invention have no toxic effect on the organisms of warm-blooded laboratory animals (rodents and dogs) under acute and chronic administration conditions of 3 months.

The daily sub-acute (30 days) and chronic (90 days) administration of the formulations to experimental animals does not show a detrimental effect on the essential physiological systems (neurological, cardiovascular, hematopoietic, secretory, respiratory), metabolism, general condition, development and fundamental homeostasis parameters of the organism at doses exceeding 20-30 times those recommended for humans.

Since the main side effect of synthetic anti-inflammatory agents is their ulcerogenic effect on the gastric mucosa, the agents of the present invention were studied in advance in order to evaluate the possibility of said phenomenon. The studies carried out showed that no ulcerogenic effect on the gastric mucosa and intestine of rats was shown during mono (4000mg/kg) and sub-chronic (800, 1600 and 4000mg/kg) administration of the formulation. During histological studies of the stomach and small intestine, no inflammatory and destructive changes were observed. Furthermore, no irritating effects on the gastrointestinal tract were observed relative to both rodents and non-rodents, indicating the safety of the formulation.

Studies of the effect of this formulation on the immune system have shown that it can be used as an immunomodulator. Stimulation of function is often expected by administering the formulation at a dose of 20mg/kg, whereas a decrease in the intensity of the immune response is expected when administered at a dose of 500 mg/kg. The ability of the formulation to stimulate an important factor of non-specific resistance of phagocytes was revealed because the number of phagocytes increased after intragastric administration at a dose of 500 mg/kg.

As a result of studying the possible allergenic effects of the formulation on male and female guinea pigs, it was shown that it does not elicit the usual allergic reactions. Conjunctival test, mast cell degranulation and immune complex response were negative. These data enable to conclude that the formulation of the invention has no sensitization in case of intragastric administration.

In animals suffering from immunosuppression (long-term congestion) caused by emotional stress, dysregulation of the development of the humoral immune response and a decrease in macrophage functional activity can be prevented by intragastric administration of a 500mg/kg dose of the formulation for 10 days.

Thus, the complex formulation of the present invention, which contains as an active ingredient the dried boswellia extract dissolved in the siberian lycopodium and turmeric oil extracts, has a remarkable anti-inflammatory activity, qualitatively different from the non-steroidal agents in terms of ulcerogenic loss and presence of immunomodulating and antioxidant activities, showing an increased organism protective function.

Industrial applicability

The present formulation can be suggested for the combined treatment of different inflammatory diseases such as arthritis, osteoarthritis, rheumatoid arthritis, post-traumatic pain syndrome and in the form of a biologically active food additive as a comprehensive enhancer.

Claims (7)

1. An anti-inflammatory extract, wherein said extract comprises dried boswellia extract or its derivatives in a vegetable oil carrier in the following ratios:

dried Boswellia carterii extract or its derivatives up to 40g

Vegetable oil carrier up to 100 ml.

2. An anti-inflammatory agent, wherein said agent comprises a dried boswellia extract contained in a vegetable oil extract produced from the seeds of pinus sibirica and turmeric root in the following compositional ratio:

dried Olibanum extract 5-40g

Oil extracts of the seeds of Pinus sibirica and Curcuma rhizome were up to 100 ml.

3. The medicament of claim 2, wherein the medicament is provided in the form of a soft gelatin capsule.

4. A process for the manufacture of a medicament as claimed in claim 2, comprising soaking whole pinus sibirica seeds in an aqueous-alcoholic solution, followed by mixing the seeds with a vegetable oil extract in a volume ratio not exceeding 1: 20, thereby obtaining a pine seed oil extract, pre-grinding turmeric roots and sieving, mixing the roots with the pine seed oil extract in a volume ratio not exceeding 1: 10 and extracting to obtain pine seeds and turmeric root oil extract, adding dry mastic extract in an amount of 5-40g/100ml oil extract and maintaining the mixture until the desired product is completely dissolved.

5. A process for the manufacture of a medicament as claimed in claim 2, wherein the extraction of the components is carried out by a rotary-pulsating process at a temperature not exceeding 50 ℃, followed by standing and filtration of the oil extract.

6. An anti-inflammatory agent characterized in that it is a gelatin capsule containing lecithin, butylated hydroxytoluene, alpha-tocopherol acetate, ascorbyl palmitate, dried boswellia extract in siberian pine seed and turmeric oil extract in the following mg/capsule component ratios:

dried Olibanum extract 25-35

250-280 extract of pinus sibirica seed and turmeric root oil

0.30-0.35 of alpha-tocopherol acetate

Ascorbyl palmitate 0.75-0.85

Lecithin 0.15-0.25

0.01-0.02 parts of butyl hydroxy toluene.

7. The medicament of claim 2 for use as a biologically active additive.