WO1999055351A1 - Herbal composition and medicament against diabetes mellitus type ii manufactured thereof - Google Patents
Herbal composition and medicament against diabetes mellitus type ii manufactured thereof Download PDFInfo
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- WO1999055351A1 WO1999055351A1 PCT/HR1999/000008 HR9900008W WO9955351A1 WO 1999055351 A1 WO1999055351 A1 WO 1999055351A1 HR 9900008 W HR9900008 W HR 9900008W WO 9955351 A1 WO9955351 A1 WO 9955351A1
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/60—Moraceae (Mulberry family), e.g. breadfruit or fig
- A61K36/605—Morus (mulberry)
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/13—Coniferophyta (gymnosperms)
- A61K36/14—Cupressaceae (Cypress family), e.g. juniper or cypress
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/28—Asteraceae or Compositae (Aster or Sunflower family), e.g. chamomile, feverfew, yarrow or echinacea
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/28—Asteraceae or Compositae (Aster or Sunflower family), e.g. chamomile, feverfew, yarrow or echinacea
- A61K36/288—Taraxacum (dandelion)
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/45—Ericaceae or Vacciniaceae (Heath or Blueberry family), e.g. blueberry, cranberry or bilberry
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/48—Fabaceae or Leguminosae (Pea or Legume family); Caesalpiniaceae; Mimosaceae; Papilionaceae
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/51—Gentianaceae (Gentian family)
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/84—Valerianaceae (Valerian family), e.g. valerian
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
Definitions
- This invention refers to the field of pharmacy, and more closely, it refers to the medicament against diabetes mellitus type II, and even more precisely, it refers to the medicament against diabetes mellitus type based on a herbal composition as an active substance.
- the subject invention is marked with the classification symbol A 61 K 35/78 - Medical preparations containing substances or products of their reactions with undefined composition, whereby substances from herbs are in question.
- the technical problem consists in finding a medicament for diabetes mellitus type II which will have the following characteristics: 1 ) that it is suitable for peroral application; 2) that even very high values of glucose concentration in blood can be reduced to or near its normal value; 3) no evident harmful side effects occur even in case of large daily doses, and even in case of a long-time use; and 4) that its effectless is not caused by a strict diet.
- Insulin a hormone produced by the pancreas, makes glucose available to cells in the human body for the purpose of obtaining energy.
- the pancreas produces little insulin or it does not produce it at all and insulin must be injected daily so that a diabetic would survive.
- the pancreas produces insulin, but the quantity of insulin is insufficient or it is less effective due to the cellular resistence, or both.
- the basic defects to which these abnormalities can be attributed are: 1 ) the reduced entering of glucose into various "peripheral" tissues; and 2) the increased releasing of glucose from the liver into the bloodstream (increased liver glucogenesis). Therefore, there is an extracellular surplus of glucose and an intracellular lack of glucose, which can be called "starving amidst abundance".
- the class of sulphonylureas includes, e.g. chlorpropamide (the trade name: Meldijan, etc.), carbutamide (some 40 trade names), glybenchlamide (trade names: Euglukon, Glibenklamid Genericon, etc.), etc.
- the group of biguanides includes, e.g. phenyl-ethyl-biguanide (trade names: Phenformin, DB- Comb, etc.), dimethyl-biguanide (trade names: Gluchopage, etc.), etc.
- a herbal composition made from the following dried ingredients: the plant of centaury (Centaurii herba), the root of dandelion (Teraxaci radix), the fruit of juniper (Juniperi communis fructus), the plant of nettle (Urticae herba), the root of nettle (Urticae radix), the root of chicory (Cichorii radix), the leaf of black mulberry (Mo s nigra folium), the flower of yarrow (Achilleae millefolii flos), the leaf of bilberry (Vaccinii myrtilli folium), the pod of beans (Phaseoli fructus sine semeni) and the root of valerian (Valerianae
- centaury Centaurii herba 12.3 % by wt. the root of dandelion (Teraxaci radix) 97 % by wt. the fruit of juniper (Juniperi communis fructus) 6.2 % by wt. the plant of nettle (Urticae herba) 7.4 % by wt. the root of nettle (Urticae radix) 7.0 % by wt. the root of chicory (Cichorii radix) 17.7 % by wt. the leaf of black mulberry (Morus nigra folium) 7.4 % by wt.
- the flower of yarrow (Achilleae millefolii flos) 3.5 % by wt. the leaf of bilberry (Vaccinii myrtilli folium) 6.6 % by wt. the pod of beans (Phaseoli fructus sine semeni) 14.4 % by wt. the root of valerian (Valerianae officinalis radix) 7.8 % by wt.
- Centarium umbellatum Gentianaceae - centaury
- TIME AND WAY OF COLLECTING it is picked during blossoming and dried in the air.
- ACTIVE SUBSTANCES small quantity of bitter substances (centapicrine, svertiamarine, sveroside and gentiopicroside).
- the drug contains up to 0.4% of flavonoid, methoxylized xanthone derivatives: methyl-belidifolin, phenol-carboxylic acid, triterpenes, triterpenes, sterols. 2-hydroxy- and 2.5-dihydroxy-terephthalic acid are present in surrounding parts and the root.
- INDICATIONS due to bitter substances, it is used to stimulate the appetite and the secretion of the gastric juices (particularly in chronical dyspeptic conditions and acheilia).
- SPREAD a plant growing wild across the northern hemisphere, with many different kinds; it is collected wild and cultivated, mostly in countries of Eastern Europe.
- CURATIVE PART OF THE PLANT part above the earth and root.
- TIME OF BLOOMING March-May.
- TIME AND WAY OF COLLECTING it is picked in April and May. It is dried in the air or at an artificial temperature of 40°C.
- ACTIVE SUBSTANCES bitter substances called taraxacyne: tetrahydroridentin B and taraxacolide ⁇ -D-glucopyranoside, and similar new germakranolides (taraxic ⁇ -D-glucopyranoside and 11 ,13-dihydrotaraxine acid of ⁇ -D-glucopyranoside, triterpenes (taraxasterol, ⁇ -taraxasterol, their acetates and 16-hydroxy-derivates amidol and faradiol), sterols (sitosterol, stigmasterol), carotenoids (xanthophyls), flavonides (apygenin), carbohydrates (in the root, containing about 1 % of slime). In spring, the drug contains 18% of sugar (fructose), and 2% of inulin, which by autumn reaches even up to 40%.
- INDICATIONS mild choleretic, diuretic, appetite stimulant (bitter substances), as adjuvant in case of liver disturbances and troubles with gall-bladder, and in case of digestive disturbances (particularly in case of incomplete digestion of fat).
- appetite stimulant bitter substances
- it is used for "cleansing of blood”
- mild laxative in case of arthritis and rheumatic troubles, rash and other skin problems.
- tea it is used as juice obtained by pressing fresh plants.
- Diuretic and saluretic effect of the fluid tincture was recently proved on rats. The effect was similar to the effect of furosemides, and stronger than other vegetable diuretics (Equiseti herba, Juniperi fructus) and that without toxic side effects.
- ACTIVE SUBSTANCES 0.5-2.0% of etherical oil, with over seventy isolated ingredients: the main component are monoterpenes: ⁇ - and ⁇ -pinene (16.5-80%), sabinene (0.2-50%), limonene (1 -12%), terpinene-4-ol, borneol, geraniol, ⁇ -terpineol. Sesquiterpenes, phenols and ethers are present in traces.
- COUNTERINDICATIONS pregnancy and inflammatory kidney processes.
- TIME AND WAY OF COLLECTING leaves are collected from May to August and dried in the air.
- ACTIVE SUBSTANCES flavonoides (glycosides of quercetin, rhametin in flowers), chlorophyl A and B, caretonides (including ⁇ -carotene and xanthophyl), vitamins
- INDICATIONS diuretic. Two weeks treatment increases the volume of urine and reduces the body weight.
- the greenness of the nettle prepared as tea or juice is used in many ways: internally as a diuretic, in case of rheumatism and arthritis, as a component of "antidiabetic" tea, for quicker healing of wounds. Externally in case of seborrhea and against the loss of hair.
- TIME OF BLOOMING June-September.
- TIME AND WAY OF COLLECTING the plant is collected in the beginning of summer and dried in the air, and the root is dug out in late autumn, it is to be well washed, cut longitudinally and dried in the airy and dry place.
- ACTIVE SUBSTANCES the root contains inulin, free fructose, glycoside intubin, tannin. The stalk and flowers contain glycoside chicorin.
- INDICATIONS choleretic, diuretic, for improving of appetite.
- ACTIVE SUBSTANCES calcium carbonate, asparaginic acid, adeninde, glucose, peptone. 8. Millefoli herba
- TIME AND WAY OF COLLECTING during the blossoming, blooming plants are collected and dried in bundles. Thickened parts are removed.
- ACTIVE SUBSTANCES 0.2-1 % of etheric oil which can, but need not contain kamasulen (depending on the number of chromosomes - only tetraploid plants contain kamasulen, and most of other karyotypes do not).
- the content of the etherical oil is the following: monoterpenes (linalool), sesquiterpenes, camphor (18%), sabinene (12%), 1.8-cineole (10%), isoartemisia-ketone (9%) and ⁇ -pinene (9%).
- Etherical oil which contains kamasulen has the following contents: monoterpenes, sesquiterpenes, kamasulen (25%), ⁇ -pinene (23%), caryophyllen (10%) and ⁇ -pinene (5%).
- achillicine 8-acetoxy- artabsine.
- guaianolides 2,3-dehydrodesacetoxy- and 8-desacetyl- matricine and ieucodine 3-oxaguaianolides 8-acetyl- and 8-angeloilegelolid
- germakranolides milefine dihydroparthenolides, balhanolid- acetate, etc.
- phenolic acid triterpenes and sterols
- cis- and frar/s-matricaria ester guaianolides 2,3-dehydrodesacetoxy- and 8-desacetyl- matricine and ieucodine
- 3-oxaguaianolides 8-acetyl- and 8-angeloilegelolid germakranolides milefine, dihydroparthenolides, balhanolid- acetate, etc.
- ACTIVE SUBSTANCES catecholic tannins (0.8-6.7%), leucoanthocyanides, flavonoids (mostly glycosides of quercetin), phenol-carboxylic acids, iridoides. The presence of chrome, alkaloids mirtin and epimirtin was noticed, while arbutin and hydrokinin are found only in traces.
- TIME AND WAY OF COLLECTING completely ripe pods are collected. Seeds are removed, and the pod is dried in the sun.
- ACTIVE SUBSTANCES albumins, carbohydrates, various amino acids, chrome salts, silicic acids.
- ACTIVE SUBSTANCES 0.3-0.7% of etherical oil, most represented ingredient is in general bornyl acetate, but other sesquiterpenes are also present: ⁇ -caryophyllene, valerenal, valeranon. 12
- valepotriate valerian epoxy-triester
- bicyclic iridoid-monoterpene There are most valtrates and isovaltrates. dihydrovaltrate and IVHD-valtrate (isovaleryl-oxyhydroxydidrovaltrate).
- Valeric acid and acetoxyvaleric acid 0.8-0.3%) are characteristic ingredients of the officinal drug - they are not found in other kinds of valerian.
- the root contains a very small percentage (0.01-0.05%) of alcaloids such as valerianin and ⁇ -methylpyril-ketone.
- INDICATIONS sedative effect (etheric oil, valepotriats), spasmolytic and muscle relaxant (valeric acid). Valeric acid and related sesquiterpenes inhibit degradation of an imortant neurotransmitter ⁇ -aminoteraxaci acid. Tea from valerian root is used for calming, relaxation, then, in case of nervous tenseness, difficulties with sleeping (but only as an auxiliary, and not as a sleep-inducing agent) and the state of stress.
- valepotriats or tinctures standardized according to the requests of valepotriats are used as tranquilizers and timoleptics
- Such preparations which always contain a mixture of valepotriats are mostly made from other kinds of valerian.
- Such preparations are used for healing of psychomotoric and psychosomatic difficulties, in case of stress or anxious states, and in case of reduced concentration.
- the medicament i.e. tea, a herbal tincture and a pill, obtained from the herbal composition, presented in Table 2, the following can be said:
- the medicament has a very strong hypoglycemic effect, comparable to that of insulin, so that the recommended doses should be strictly observed.
- the concentration of glucose in blood could be reduced even by 6 mmol/l 13
- this medicament also reduces the level of cholesterol at the same time. Also, it restores the disturbed metabolism of carbohydrates and fats. Furthermore, it removes all the visible symptoms of manifested diabetes mellitus type II. Among other things, it restores physical strength. It heals diabetes II when other antidiabetics are already weak. Consequences harmful for health have not been noticed.
- the medicament is effective even without a strict diabetic diet.
- a further advantage of this herbal tincture which should be pointed out in particular, is the fact that women can use it even during pregnancy. It was noticed, however, that consuming nicotine, alcohol and caffeine reduces the effectiveness of the medicament and causes the prolongation of the treatment; consumed in extreme quantities, they particularly unfavourably effect the treatment.
- the tea from the herbal composition is obtained by this process:
- the herbal composition made of dried and cut ingredients according to Table 1 or Table 2, is to be covered with boiling water, where the mass of the herbal composition and the mass of water are in the proportion 1-2:75. Then it should be left to rest in a covered container for 20 minutes, and then it should be filtered.
- the above proportion of masses corresponds to covering of 1-2 spoonfuls of the herbal composition with 3 dl of boiling water. 14
- the herbal tincture from the herbal composition is obtained in the following way: the herbal composition which is made of dried and cut ingredients according to Table 1 or Table 2 is to be covered in 60% ethanol at the room temperature, whereby on 1 kg of the herbal composition 7.21 I 60% ethanol are to be used. For the purpose of extraction, the mixture is left to rest for 28 days in a covered container, at the room temperature and pressure. The herbal tincture is then obtained by decanting the liquid above the sediment.
- the optimum speed of the reduction of the concentration of glucose in the blood is, approximately, from % mmol/l up to ⁇ mmol/l, that is, averagely 1/3 mmol/l daily.
- % mmol/l up to ⁇ mmol/l that is, averagely 1/3 mmol/l daily.
- the active substance for the pill from the herbal composition is obtained according to the following process: the herbal composition, made of dried and cut ingredients according to Table 1 or Table 2, is dissolved in 60% ethyl alcohol.
- the herbal composition made of dried and cut ingredients according to Table 1 or Table 2
- the mixture is left to rest for 28 days, in a dark place, at the room temperature and pressure.
- the alcoholic tincture obtained in that way was exposed to evaporation in the vacuum of 10 mmHg in the timely linear temperature gradient from 20°C to 40°C during the time of 30 minutes.
- the quantity of 50 ml alcoholic tincture was mixed with 0.5 g of nonionogenic co-solubilizer of hydrophilic tenside (e.g.
- This fine powder is an active substance which is used for production of the pill. It meets the basic conditions for pilling, because the experiments on animals showed that the high pressure, which can cause the plastic deformation of particles and the deformation of intramolecular forces, did not disturb its biological activity.
- the pill was prepared in the following way: 60 mg of the active substance in form of fine powder, which contains all the ingredients of the extracted herbal composition, is mixed with 180 mg of the natural zeolite, which is tribo-activated and in a microcrystalic form, very stable and with the pH-value from 1 to 11.
- the natural zeolite which is tribo-activated and in a microcrystalic form, very stable and with the pH-value from 1 to 11.
- 35.0 mg of monosaccharides was added to the mixture obtained in such a way.
- the mixture made in such a way was mixed with the natural clarified microcellulose in the dose of 80 mg, which allows plastic deformation.
- Mg-stearate in the dose of 5.0 mg was added, for obtaining of a better slipping quality.
- the quantity content of the pill is clearly shown in Table 3.
- the homogenous mixture prepared in such a way was compressed by the method of direct compressing, which is the method of choice for pilling of moisture sensitive and thermolabile
- Natural zeolite ... 180.0 mg 50.0 % by wt.
- Monosaccharides 35.0 mg 9.7 % by wt.
- the patient On the fourth day, and onwards, the patient drank the upper dose twice a day, in the morning and in the evening, half an hour before a meal (that is, 2 x (2 x 4 g)/3 dl/day, i.e. 16 g/6 dl/day).
- the patient drank the tea made from 2 spoonfuls of the herbal composition and 3 dl of water (that is, 3 x (2 x 4 g)/3 dl/day, i.e. 24 g/9 dl/ day) three times a day, half an hour before a meal.
- the patient drank the tea made in the way described above twice a day, in the morning and in the evening, half an hour before a meal (that is, 2 x (2 x 4 g)/3 dl/day, i.e. 16 g/6 dl/day).
- concentration of glucose in the blood fell to 6 mmol/l. That level of glucose in the blood was maintained by taking of 1 teaspoon of the herbal tincture daily (5 ml/day).
- the patient was physically moderately active and he was on a very weak diet.
- the patient drank 10 ml of the herbal tincture a day (30 ml/day) three times a day and a dose of the tea made from 2 spoonfulls of the herbal composition and 3 dl of water (that is, 3 x (2 x 4 g)/3 dl/day, i.e. 24 g/9 dl/day).
- the daily doses, both, of the tea, and of the herbal tincture were reduced by a dose, so that the patient continued drinking 10 ml of the herbal composition (20 ml/day) twice a day, and a dose of the tea made in the way mentioned above twice a day, in the morning and in the evening, half an hour before a meal (16 g/6 dl/day).
- the daily dose of Euglucon was gradually reduced. After the fifteen days of treatment in all, the level of glucose in the blood fell to 7.0 mmol/l, and the daily dose of Euglucon was reduced to 1 pill.
- the achieved level of glucose in the blood was maintained ba the therapy consisting of 1 teaspoon of the herbal tincture daily (5 ml/day) or of one dose of the tea made in the way described above (2 x 4 g/3 dl/day).
- the patient drank 10 ml of the herbal tincture (30 ml/day) and three times a day, half an hour before a meal, a dose of the tea made from 2 spoonfuls of the herbal composition and 3 dl of water (that is, 3 x (2 x 4 g)/3 dl/day, i.e. 24 g/9 dl/day).
- both, of the tea, and the herbal tincture were reduced by one dose, so that the patient kept on drinking 10 ml of the herbal tincture (20 ml/day) twice a day, and a dose of the tea prepared in the way described above twice a day, in the morning and in the evening, half an hour before a meal (16 g/6 dl/day).
- the level of glucose dropped to 9.98 mmol/l, and cholesterol was reduced to 4.41 mmol/l.
- the achieved level of glucose in the blood was maintained by the therapy consisting of 21
- the patient drank 10 ml of the herbal tincture (30 ml/day) three times a day and one dose of the tea prepared from 2 spoonfulls of the herbal composition and 3 dl of water (that is, 3 x (2 x 4 g)/3 dl/day, i.e. 24 g/9 dl/day) three times a day.
- the patient drank 10 ml of the herbal tincture (30 ml/day) and a dose of the tea prepared from 2 spoonfulls of the herbal composition and 3 dl of water (that is, 3 x (2 x 4 g)/3 dl/day, i.e. 24 g/9 dl/day) three times a day.
- the effect of the perparation made according to this invention on the level of glucose in diabetic mice with respect to the time of probing was studied. All doses which were applied on rodents were adjusted to the concentration of proteins in the preparation made according to the invention. The concentration of proteins in the preparation made according to the invention was determined by the method by Bradford. To the determination of the concentration of proteins were subjected the tea, the tincture (after the elimination of alcohol), and the lyophilized sample. The concentration of glucose in CBA diabetic mice (18 mice per group) before the treatment with the preparation made according to the invention on the average amounted to 22.4 ⁇ 6.5 mmol/l.
- mice were receiving it daily in food in the amount of 20 mg/kg body weight/day.
- mice spent 24 hours in metabolic cages (Table 4). During the 24 hours, the quantity of the eaten food, the drunk water, the excreted urine and feces was measured. From the results obtained it turns out that during the 24 hours, on the average, one mouse ate about 5.37 ⁇ 1.08 g of food, drunk 2.94 ⁇ 1.02 ml of water and excreted 1.14 ⁇ 0.28 g of feces, and urinated 1.2+0.4 ml of urine.
- mice Group Food (g) Water (ml) Feces (g) Urine (ml) of mice
- the effectiveness of the pill regarding the hypoglycemic effect was ascertained on diabetic mice. Diabetes was caused by a single injection of Alloxan (75 mg/mouse/kg of body weight). 14 days later, all the diabetic mice were included in the experiment. A zero sample of blood was taken from diabetic mice and the quantity of glucose in the blood was measured, which is shown in Table 8 and Figure 2 as 100%. The preparation of the pill was introduced by a probe to diabetic mice, per os, in the dose of 20 mg of the active substance/mouse/kg of body weight. In the first 30 minutes, the concentration of glucose in the periferal blood of the treated diabetic mice was reduced on the average by about 11 % (Table 8).
- NOD mice are a kind of mice in which diabetes was developed spontaneously.
- the results of the test of assimilation of glucose are presented in Figure 3. It shows that, after 120 minutes, the diabetic mice fed with the preparation of the pill according to the invention had a considerably reduced concentration of glucose in the peripheral blood in relation to the control diabetic mice, designated with "Diabetes".
- the designation "Control” in Figure 3 refers to non-diabetic mice.
- mice in the quantity of 5 mg of the active substance per one gram of food.
- variations of the body mass of mice was observed on the days: 7 th , 14 th , 30 th , 60 th , 120 th and 180 th from the beginning of such diet.
- the mice were placed in the metabolic cage during 24 hours, which enabled the determination of the quantity of food eaten by each mice, the quantity of water drunk, and the mass of feces and the volume of the excreted urine.
- Table 9 The results are shown in Table 9 and from them it is evident that the application of the preparation according to the invention did not disturb the health of treated mice during 6 months.
- mice Food g) Water (ml) Feces (g) Urine (ml)
- mice After the 180 th day the mice were sacrificed in ether narcosis, various organs were taken out of them and they were subjected to histological processing and later detailed examination under the light microscope. No pathological changes on the examined organs, both, on the control ones, and on those from the mice fed with the invention prepared in form of a pill.
- mice After adding of all the ingreadients of the pill to the food, the healthy mice were daily fed with such a mixture i the quantity of about 20 mg of the active substance per mouse. In this group of mice the tests already stated above were simultaneously carried out as well, which, as those with mice which were taking food without the added pill for a long time, showed that there were no toxic consequences of the application of pills during 6 months period and at the end of it.
- the results are presented in Table 11. The results show that there were no changes in the concentration of the measured parameters during 6 months (Table 11 ). The value of aspartate amino transferase was somewhat raised during the first 7 days, which can be explained by adjustment of the mice to the new type of diet (maybe a little hunger was present during the first 7 days). But, after 6 months there are no sigs of changes (Table 11 ).
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CA002367888A CA2367888A1 (en) | 1999-03-12 | 1999-04-22 | Herbal composition and medicament against diabetes mellitus type ii manufactured thereof |
AU36220/99A AU781092B2 (en) | 1999-03-12 | 1999-04-22 | Herbal composition and medicament against diabetes mellitus type II manufactured thereof |
JP2000545549A JP2002534354A (en) | 1999-03-12 | 1999-04-22 | Herbal composition and drug prepared therefrom for type II diabetes mellitus |
BR9917211-9A BR9917211A (en) | 1999-03-12 | 1999-04-22 | Herbal composition and medication against type 2 diabetes mellitus manufactured from the same |
GB0124592A GB2363714B (en) | 1998-04-23 | 1999-04-22 | Herbal composition and medicament against diabetes mellitus type II manufactured thereof |
US09/952,055 US6576270B2 (en) | 1999-03-12 | 2001-09-11 | Herbal composition and medicament against diabetes mellitus type II manufactured thereof |
US10/426,476 US7056539B2 (en) | 1999-03-12 | 2003-04-30 | Process and product extracted from herbal composition useful in controlling diabetes mellitus type II |
Applications Claiming Priority (4)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
HRP980109 HRP980109B1 (en) | 1998-04-23 | 1998-04-23 | Herb mixture and a medicine against diabetes melitus type ii. obtained therefrom |
HRP980109A | 1998-04-23 | ||
HR990080A HRP990080B1 (en) | 1999-03-12 | 1999-03-12 | Plant mixture and a medical preparation for the treatment of diabetes mellitus, type ii, obtained therefrom |
HRP990080A | 1999-03-12 |
Related Child Applications (1)
Application Number | Title | Priority Date | Filing Date |
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US09/952,055 Continuation US6576270B2 (en) | 1999-03-12 | 2001-09-11 | Herbal composition and medicament against diabetes mellitus type II manufactured thereof |
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WO1999055351A1 true WO1999055351A1 (en) | 1999-11-04 |
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PCT/HR1999/000008 WO1999055351A1 (en) | 1998-04-23 | 1999-04-22 | Herbal composition and medicament against diabetes mellitus type ii manufactured thereof |
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GB (1) | GB2363714B (en) |
WO (1) | WO1999055351A1 (en) |
Cited By (14)
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WO2001095920A1 (en) * | 2000-06-16 | 2001-12-20 | Basic, Robert | Composition comprising clinoptolite, plant extracts and vitamin b complex for diabetic neuropathy |
JP2002027946A (en) * | 2000-07-14 | 2002-01-29 | Pola Chem Ind Inc | Mineral absorption promoter and composition containing the same |
JP2002187847A (en) * | 2000-12-21 | 2002-07-05 | Pola Chem Ind Inc | Composition for supplying calcium |
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WO2003013563A2 (en) * | 2001-07-06 | 2003-02-20 | Robert Basic | Mineral-protein preparations (mpp) and neuropathies in diabetes |
WO2003053167A1 (en) * | 2001-12-11 | 2003-07-03 | Societe Des Produits Nestle S.A. | Composition for promotion of bone growth and maintenance of bone health |
WO2003053166A1 (en) * | 2001-12-11 | 2003-07-03 | Societe Des Produits Nestle S.A. | Food or pet food composition containing plant extract for bone health |
JP2005504753A (en) * | 2001-07-27 | 2005-02-17 | メルク パテント ゲゼルシャフト ミット ベシュレンクテル ハフトング | Bauhinia extract |
WO2005034973A1 (en) * | 2003-10-10 | 2005-04-21 | Vladimir Leko | Capsulated herbal composition as auxilary medicament against diabetes mellitus type (i) and (ii) |
WO2006122541A2 (en) * | 2005-05-18 | 2006-11-23 | Tihomir Lelas | Pharmaceutically effective composition for treating diabetes |
WO2008142460A2 (en) * | 2007-05-18 | 2008-11-27 | Leko Vlado | New herbal composition for prevention and treatmant of diabetes melitusa of type (i) and type (ii) |
US7527794B2 (en) | 2001-07-31 | 2009-05-05 | Wayne State University | Hybrid proteins with neuregulin heparin-binding domain for targeting to heparan sulfate proteoglycans |
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RU2802832C1 (en) * | 2022-11-15 | 2023-09-04 | Федеральное государственное бюджетное образовательное учреждение высшего образования "Самарский государственный медицинский университет" Министерства здравоохранения Российской Федерации | Use of hyperozide as a diuretic, saluretic and creatininuretic agent |
Citations (1)
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JPH0717856A (en) * | 1993-06-30 | 1995-01-20 | Tsumura & Co | Aldose reductase-inhibiting agent |
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1999
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- 1999-04-22 GB GB0124592A patent/GB2363714B/en not_active Expired - Fee Related
Patent Citations (1)
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JPH0717856A (en) * | 1993-06-30 | 1995-01-20 | Tsumura & Co | Aldose reductase-inhibiting agent |
Non-Patent Citations (2)
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PATENT ABSTRACTS OF JAPAN vol. 095, no. 004 31 May 1995 (1995-05-31) * |
SARA K. SWANSTON-FLATT ET AL.: "Glycaemic effects of traditional european plant treatments for diabetes.Studies in normal and streptozotocin diabetic mice", DIABETES RESEARCH, vol. 10, no. 3, March 1989 (1989-03-01), pages 69 - 73, XP002112023 * |
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Also Published As
Publication number | Publication date |
---|---|
GB0124592D0 (en) | 2001-12-05 |
GB2363714B (en) | 2004-03-03 |
GB2363714A (en) | 2002-01-09 |
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