Mixture of bornyl acetate and camphene possessing cholinergic action

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to the pharmaceutical industry, namely to a cholinergic agent. A mixture of bornyl acetate and camphene taken in a certain ratio possessing the cholinergic action.

EFFECT: above mixture possesses the pronounced cholinergic action.

3 tbl, 2 ex

 

The invention concerns a mixture of barcelonetta and camphene included in the composition of essential oils of coniferous trees, such as fir and Siberian pine, and can be used in pharmacology for the treatment of diseases associated with disease of the autonomic and Central nervous system, smooth muscle cells of the gastrointestinal tract, smooth muscles of the bronchi, heart, etc. also increases the tone of the urinary bladder.

Drugs with cholinergic effects, synthetic origin, such as piracetam, arecoline hydrochloride, termopsin, platifillin, currently used for the treatment of these diseases of the CNS, have inadequate therapeutic efficacy, have a number of side effects (irritability, anxiety, insomnia, tremor, increased tendon reflexes, dizziness, diarrhoea disorders, increased coronary insufficiency, increased blood pressure, fever, allergic reactions, changes in the blood picture and the condition of internal organs) that restrict their use, especially in the face of continued employment. Funds on the basis of raw materials of vegetable origin can play a significant role in solving this problem.

Closest to the proposed solution which is a means of plant origin, namely physostigmine is the main alkaloid Calabar beans [hranik Century, fundamentals of medicinal chemistry. - 2nd ed. -M.: 2006. - 384 S.].

Identify new sources of content of biologically active substances with cholinergic action is an important direction in some sectors of production and consumption.

The objectives of this invention is the expansion of the means of combating diseases associated with the change in the activity of the autonomic and Central nervous system, derived from plant material, and to increase the cognitive abilities of the person.

The objectives are achieved through the use of a mixture of barcelonetta and camphene in the ratio 3:1 with cholinergic action.

Essential oils of Siberian fir is a complex mixture of 31 components, which are the basic barcelonetta and camphene. Thanks to contained components of the essential oil regulates the increase in the concentration of light negative ions, a positive current at the person performing the function of "providing" the atmospheric air of biologically active oxygen, and which have a beneficial effect on the emotional state of the person.

CAMPHENE is the only crystalline hydrocarbon found in natural essential oils. Occurs quite frequently is, but in small quantities in two optically active and racemic forms.

Defined in the oil, Siberian pine, Siberian fir, cypress, camphor, lemon, orange, lavender-spice, nutmeg, ginger, Ceylon citronella, Valerian. Easily subjected intramolecular rearrangements. Attaching a molecule of water, he turns into borneol and, mainly, isoborneol, and an intermediate product of this hydration is a tertiary alcohol - companythat. Oxidation of camphene leads to the formation of campiglione, campanulas and companylevel acids, which then give Campanile. Easily gives different binary chemical mixtures with other compounds. Synthetic camphene and enriched fractions of natural essential oils containing camphene used for low-grade flavors and fragrances in technical applications.

BARCELONETTA is an important component of the essential oil of some conifers: Abies alba, Pinus pumilo, P. sylvestris. In the essential oil of Siberian fir needles contains 30-40% of barcelonetta. Also found in the essential oil of coriander and Valerian root. Barcelonetta has the typical smell of pine needles with notes of freshness, and therefore is widely used for scenting Soaps, inhalers, sprays bath. Sometimes used in medical preparations.

Essential oil derived from wood green is neither coniferous trees, antiseptic, anti-inflammatory, antispasmodic, sedative, analgesic, antiulcer and wound healing properties [Coniferous healers / Yu, tigilau [and others] - Khabarovsk: publishing house HCCPS, 2004. - 52 S.].

It is known that biologically active substances contained in essential oils of Siberian fir, including barcelonetta and camphene, have antiaksidantnymi activity, inhibit the growth of infections, viruses, possess diuretic, stimulant and tonic effect (U.S. Pat RF 2426452). In addition, barcelonetta has growth-stimulating and antifungal properties (U.S. Pat. Of the Russian Federation No. 2469539, 2199861). Known balsamic tool containing barcelonetta with antimicrobial, anti-inflammatory and analgesic effect (U.S. Pat RF 2088214).

In the available sources of scientific, technical and patent information is not revealed information about cholinergic activity barcelonetta and camphene - the main components of essential oils of coniferous trees. Therefore, the proposed solution is novel and meets the criteria of patentability "inventive step".

In the literature rare joint description of the composition of the essential oil and its biological action. Mentioned essential oil as such and refers to its biological properties, thus completely missing the ut data about the chemical composition of the sample, carried out certain tests. Detection of biological activity of essential oils must be accompanied by a detailed study of their composition, selection and study of the properties of the individual components, which determine how useful properties of plants, and negative, causing side effects.

Essential oil for these studies was obtained from the wood green fir method of exhaustive hydroponically for 20 hours using all-metal installation with nozzle Clevenger. One load of dry feedstock was not less than 1,00 kg Fraction of the essential oil was collected in the process of obtaining essential oils as follows: the first fraction was obtained within 30 minutes from the start of the allocation of oil; second, after two hours; the third one - in-four hours; the fourth - after 5 hours; fifth - eight hours.

The concentration of various compounds in the process of distillation of essential oil to change. Therefore, the conducted analysis of the composition of the fractions of the essential oil collected in the process of getting from woody plant materials of Siberian fir (table.1).

borneol
Table 1
The composition of the individual fractions of the essential oil of fir CB is tion
Composition, %
ComponentFraction 1Faction 2Fraction 3Fraction 4Fraction 5
barcelonetta50,1±1,555,0±2,053,9±1,744,2±1,125,6±0,8
camphene18,3±0,618,2±0,817,2±0,313,1±0,15,4±0,2
alpha terpinene6,6±0,26,5±0,37,2±0,27,8±0,16,3±0,1
lemon7,1±0,25,7±0,45,9±0,37,5±0,20,3±0,0
alpha-pinene5,3±0,25,7±0,36,6±0,56,5±0,52,5±0,1
5,9±0,32,9±021,4±0,11,4±0,1-
α-caryophyllene--0,3±0,01,3±0,14,1±0,2
tricyclen1,2±0,01,3±0,01,5±0,11,4±0,10,5±0,0
Santen1,2±0,01,0±0,01,1±0,01,7±0,11,0±0,0
β-pinene0,7±0,00,5±0,00,6±0,01,0±0,01,1±0,0
α-terpinolene0,9±0,01,0±0,00,9±0,00,9±0,00,9±0,0
4-terpineol0,2±0,00,1±0,00,1±0,0 --
α-terpineol--0,1±0,00,2±0,00,7±0,0
α-bisabolene-0,2±0,00,8±0,05,3±0,217,9±0,4
TRANS-caryophyllene0,3±0,00,2±0,00,4±0,02,1±0,16,7±0,2
β-bisabolene0,1±0,00,2±0,00,4±0,00,5±0,02,3±0,1
longifolene0,2±0,00,1±0,00,3±0,00,9±0,00,1±0,0

The results of determining the composition of the show, the reduction in the content of some chemical compounds in the last 4 and 5 of the fraction. For example, the content of barcelonetta and camphene in the beginning of the production of the essential oil were respectively 50,0 and 18.3%, and K is NCU time distillation decreased to 25.6% and 5.4%. At the same time, components such as α-caryophyllene, α-bisabolene in subsequent fractions significantly increase.

Using a highly sensitive enzyme test systems in vitro allowed us to determine not only the biological activity of essential oils in General, and selected fractions that gave the opportunity to identify compounds with high biological activity and to determine the direction of their actions.

Cholinergic properties barcelonetta and camphene and their mixtures were determined using Biotest systems on the basis of the enzyme acetylcholinesterase (ache), in vitro, on the ratio of the rate of the enzymatic reaction on the test object after adding substance and the rate of the enzymatic reaction before adding substances that should be the case cholinergic less than the control values (<100%). And the smaller the value, the higher the cholinergic properties of the matter. [Enzymatic test system in vitro for the directed search of cholinergic drugs and study of their mechanism of action C. A. Dubinsky, M. F. Mineeva, C. E. vakhnin in capacity, L. B. Rebrov, V. A. Bykov. Problems of biological, medical and pharmaceutical chemistry, No. 2, 2007 S. 32-37]. Ache is an enzyme that catalyzes the hydrolysis of the natural neurotransmitter acetylcholine, participating in the process of momentum transfer nerve fiber is mi. Enhanced activity of acetylcholine, due to its accumulation in organs and tissues can be achieved by inhibiting ache. The ache inhibitors have a broad spectrum of therapeutic action, including cholinergic action.

A new property of a mixture of barcelonetta with camphene found in the experimental study of cholinergic action of the composition containing barcelonetta and camphene at different ratios from 2:1 to 5:1.

Distinctive features showed in the inventive combination of new properties that are not explicitly derived from the prior art in this field and obvious to the specialist. First established that as a means of elevated cholinergic effect, you can use the inventive mixture.

The proposed tool can be successfully used in medical practice for correction of pathological changes in the activity of the autonomic and Central nervous system with increased cholinergic activity, obtained from vegetable raw materials. And to increase the performance of cognitive human activity. Correctly selected fractions of essential oils will allow, in addition to saving time and money on the production, to get the most active mixture of barcelonetta and camphene. An optimal balance between osenia of barcelonetta and camphene 3:1. With a ratio of 2:1 there is a decrease in cholinergic activity. When the ratio of barcelonetta and camphene 5:1 the production of the mixture becomes uneconomic.

Example 1. The definition of the cholinergic activity of the components of barcelonetta and camphene in the essential oil of Siberian fir.

Comparing the data obtained in the chemical composition of fractions of essential oils and determination of their biological activity, it is possible to identify the main compounds affecting cholinergic action of the inventive mixture. In table.2 shows the results of determining the biological activity of the fractions of the investigated essential oils using Biotest systems in vitro.

Value of the velocity of enzymatic reactions for the control (no added essential oils) are: ache was 513.3 MK mol/ min·mg, which corresponds to 100%.

Table. 2 the Main components of the individual fractions of the essential oils of Siberian fir and their influence on the rate of enzymatic reactions.

Table 2
ComponentsThe reaction rate ache
MK mol/min*mg%
Controlwas 513.3±30,7 100
FR.179,2±1,915,4
FR.271,4±2,113,9
FR.366,0±2,512,9
FR.4132,4±11,325,8
FR.5275±11,353,7
Of whole oil138,2±5,726,9
Barcelonetta87,2±3,9of 17.0
Camphene84,2±3,616,4
Note: * - significant differences from control at p<0,05

The analyzed fractions of essential oils of Siberian fir inhibit the enzyme ache and, therefore, have a cholinergic effect. When added to the incubation medium fractions 2 and 3 speed ache reaction is higher, as substantially inhibits the enzyme: a 13.9% and 12.9% in the 2nd and 3rd faction. The reduction of the biological action of the oil in the 4-th and 5-th fraction is expressed in the reduction of the ability to inhibit the enzyme. Also clean barcelonetta and camphene have the ability to inhibit the enzyme is less than the fraction of the 4-th and 5-th essential oils.

If we compare these data with the composition of the fractions of the essential oil, it is likely that the reduced ability to inhibit ache is due mainly to the decrease of the basic components of barcelonetta and camphene and increasing the influence of impurities.

The reliability impact of barcelonetta and camphene on cholinergic activity of essential oils of Siberian fir was determined, revealing the dependence between the content of barcelonetta and camphene in the essential oil and its biological effect on ache. The reliability of influence, and thus, the identified components: barcelonetta and camphene on cholinergic activity of essential oils of Siberian fir, was 0,864 and 0,869.

Identify components (barcelonetta and camphene) with cholinergic action was based on the change in the concentration of various compounds in the process of essential oil distillation. In the essential oil of fir content barcelonetta and camphene reduced in the last 4 and 5 of the fraction. At the same time, the content of other such components as α-caryophyllene, α-bisabolene in subsequent fractions significantly increased. Comparing the data obtained in the chemical composition of fractions of essential oils and their bio is logicheskoi activity you can define basic compounds affecting cholinergic action of the inventive mixture.

Similar data were obtained when using other plant materials (pine, Siberian and Ledum palustre) to produce essential oils containing barcelonetta and camphene.

Example 2. Impact on learning and memory offer mixtures investigated in the development and reproduction of the conditioned reflex of passive avoidance (passive avoidance reaction). The technique of passive avoidance reaction /bureš J., Buresova O., Houston J. P. Techniques and basic experiments for the study of brain and behavior. - M.: Higher school, 1991. - 175-177./ based on the suppression of innate reflex preference dark space in rodents. For amnestic effects used intraperitoneal injection of a mixture of barcelonetta and camphene with a ratio of 3:1 at a dose of 1.5 mg/kg over 30 min to play passive avoidance reaction. Assessment antiamnesic effect of the investigated mixtures and reference drugs with cholinergic action of physostigmine was carried out according to two main indicators of passive avoidance reaction - latency period of time in the dark compartment and the time spent there.

The experimental set-up is the camera, consisting of two compartments - large (light) and low (dark). The animal is placed in the bright compartment and after some time it goes dark, after which the hole is Edinaya both compartments, block the door and on the floor of the dark compartment, which is a lattice of parallel stripe electrodes, serves electric current pulses with a duration of 50 MS with a frequency of 5 Hz and an amplitude of 50 mA. Through 10 with the door open and the animal can pop out in the bright compartment with a conventional floor. In the described procedure, the animals developed a conditioned reflex avoidance dark space. When checking reflex animal was placed in the camera angle light compartment, opposite from the entrance, and watched for 3 minutes Recorded time of the first entry into the dark compartment (latent time of call), the total time spent in the dark compartment, the number of animals produced by reflex. The criterion of the presence of the reflex was considered the absence of overriding the animal in the dark compartment for 3 min until the mouse light camera. The inspection of safety reflex was carried out after 24 h, 2 weeks after running out of reflex.

The proposed mixture increases the safety of the conditioned reflex of passive avoidance and contributes to the reproducibility of the reflex to 100% when testing after 24 h, 14 days after production in normal animals (table.3).

Table.3
Group observations dose The proportion of animals with preserved reflex in check, %Note
24 h after generation14 days after making out
Intact control4040behavioral despair
Barcelonetta:
Camphene=3:1
10090motor activity, muscle tone
Fir essential oil7560Lethargy, slowness of movement
Barcelonetta8065Lethargy, slowness of movement
Camphene7560Lethargy, slowness of movement
Similar physostigmine8560Side effects is a disorder of the gastrointestinal tract

Thus, the study showed that most in the expression of cholinergic action of a mixture of barcelonetta and camphene in the ratio 3:1 on some indicators of the state of the Central nervous system of experimental animals (increased safety of the conditioned reflex of passive avoid if there is no effect on locomotor activity in normal animals).

On the basis of experimental studies it can be concluded that the use of products containing a mixture of barcelonetta and camphene, is promising to obtain a higher therapeutic effect.

The positive effect achieved through the use of mixtures containing barcelonetta and camphene, as drugs with cholinergic activity, which expanded the Arsenal of tools with high specific activity.

As a result of researches it is established, that on a background of application of the inventive mixture of barcelonetta and camphene in acute Central nervous system disorders in cerebrovascular disease of various etiologies is the reconstruction of functional norms memory, behavioral and motor activity, muscle tone and elimination of symptoms severity of neurological deficits with full recovery of neurological status during the course of administration of the drug at a sufficiently early stages of the disease.

A mixture of barcelonetta and camphene in the ratio 3:1 with cholinergic effects.



 

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FIELD: medicine.

SUBSTANCE: invention refers to medicine, namely to dentistry. A method for the conservative treatment of parodontium involves applying a treatment wrap prepared of zinc oxide and zinc sulphate; applying the treatment wrap is preceded by a multiple irrigation of parodontium tissues with butol solution; the treatment wrap is prepared by adding zinc oxide powder and zinc sulphate powder into butol solution and mixing them to pasty consistency; dental tissues from the vestibular and oral surfaces in the neck region are covered with a gauze drain of the diameter of 1-4mm saturated with butol solution; parodentium and dental tissues covered with the gauze drain saturated with butol solution is coated with the treatment wrap.

EFFECT: using the method enables achieving optimum diffusion of the therapeutic preparation in the parodontium tissue and its prolonged effect on parodontal tissues, with providing haemostatic effect and adequate anti-inflammatory action.

2 ex

New composition // 2538718

FIELD: medicine, pharmaceutics.

SUBSTANCE: group of inventions refers to a dental cleaning composition and a method for preparing it. The dental cleaning composition contains calcific aluminium oxide as a polishing agent containing 50 to 90 wt % of aluminium α-oxide and 10.0 to 50 wt % of aluminium γ-oxide in an amount of 0.1 to 3.0 wt % of the total composition, water-soluble tripolyphosphate alkali salt and orally acceptable carrier or excipient with the composition being free from silicone dioxide abrasive. A method for preparing the composition involves mixing the ingredients easily in vacuum to prepare a homogenous mixture and to adjust pH if necessary.

EFFECT: using the composition enables achieving good cleaning, excellent shine and dental surface polishing with low dentine abrasion.

10 cl, 4 ex, 5 dwg

FIELD: medicine.

SUBSTANCE: pharmaceutical composition for treating demodecosis contains metronidazole, tea tree oil, polymer carrier specified in: macrogol 400, macrogol 1,500, macrogol 4,000, and distilled water in certain amounts.

EFFECT: composition treats demodecois effectively, with no side effects.

6 cl, 8 ex

FIELD: medicine.

SUBSTANCE: invention refers to medicine, namely to dentistry. A method of treating inflammatory diseases of parodentium involves administering a dosage form into gingival pockets and immersed fully underneath the gingival line; that is ensured by irrigating the gingival pockets with Dentos solution; an implant side for a medicinal thread is created by placing a retraction thread of a diameter exceeding that of the medicinal thread into the gingival pockets, or the implant side for the medicinal thread is created in the gingival pockets by scaling with an abrasion spoon or a scaler; saturated Dentos cotton medicinal thread or saturated Dentos medicinal resorbed carboxymethyl cellulose thread is introduced into the gingival pockets.

EFFECT: using the method provides the prolonged maintenance of the active substance concentration in the parodontium tissues with the active substance possessing antimicrobial and anti-inflammatory properties, and has a uniform effect along the whole perimeter of the gingival pocket that enables reducing the inflammatory process.

2 ex

FIELD: medicine, oncology, amino acids.

SUBSTANCE: invention relates, in particular, to the development of an antitumor preparation based on natural substances. Invention relates to an amino acid preparation comprising at least one modified essential amino acid obtained by treatment of amino acid by ultraviolet radiation (UV) at wavelength 250-350 nm for 12-80 h at temperature 15-30oC or with ozone at temperature 15-25oC. The modified amino acid has no toxicity for health cells. Also, invention relates to a method for preparing such preparation. Invention provides the development of an antitumor preparation based on modified amino acids and expanded assortment of antitumor preparations being without cytotoxicity for normal cells.

EFFECT: valuable medicinal antitumor properties of preparation.

8 cl, 4 tbl, 2 dwg, 4 ex

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