CN1189776A - High-dose chromic tripicolinate for the treatment of type II diabetes - Google Patents
High-dose chromic tripicolinate for the treatment of type II diabetes Download PDFInfo
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- CN1189776A CN1189776A CN 96195218 CN96195218A CN1189776A CN 1189776 A CN1189776 A CN 1189776A CN 96195218 CN96195218 CN 96195218 CN 96195218 A CN96195218 A CN 96195218A CN 1189776 A CN1189776 A CN 1189776A
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Abstract
A method for stabilizing blood glucose levels and reducing the hyperglycemia associated with Type II diabetes. Synthetic chromic tripicolinate is administered either orally or parenterally to a human in need thereof at a dosage of between about 1,000 and 10,000 micrograms per day.
Description
Invention field
The present invention relates to or the treatment of the non-insulin-dependent diabetes mellitus (NIDDM) of people morbidity.More particularly, the present invention relates to treat such diabetes by giving heavy dose of chromium that exists in the chromium picolinate mode.
Background technology
The known U.S. has at least 10,000,000 people to suffer from diabetes, and unknown patient's number can be more.In type ii diabetes, i.e. non-insulin-depending type or be called adult type (for juvenile onset diabetes), pancreas continues to secrete the insulin of normal amount usually.But insulin is invalid to the control of diabetes symptom, and these symptoms comprise that blood glucose is too high, the reduction of carbohydrate metabolism level, glycosuria and insulin sensitivity type reduce.If without treatment, these symptoms cause severe complications through regular meeting.
Chromium is the necessary trace element with nutritive value of human body, the necessity of chromium in diet put forward in nineteen fifty-nine by Schwartz, referring to " Present Knowledge inNutrition " 571 pages, the 5th edition (1984, threpsology's foundation, the Washington D.C.).Chromium deficiency can cause glucose, lipid and protein metabolism disorder, and the lost of life.Chromium remains on an optimum state also be absolutely necessary (Boyle etc., " Southern Med J., " 70:1449-1453,1977) for the insulin active in all known insulin-dependent systems.The chromium deficiency can cause adult diabetes mellitus and cardiovascular disease in the diet.
Glucose and fatty acid are the basic power source sources for body.Chromium deficiency can cause the insulin physiologic function to lose efficacy and the glucose metabolism disorder.Under this condition, the body ratio must at first rely on lipid metabolism to satisfy its energy demand, so cause the generation of excessive S-acetyl-coenzyme-A and ketoboidies.A part is gathered the S-acetyl-coenzyme-A that gets off then is participated in cholesteric biosynthesis, causes hypercholesterolemia.The feature of diabetes shows as glycosuria, hypercholesterolemia and regular ketoacidosis to a great extent.Atherosclerosis common among the diabetes patient is accelerated also relevant with hypercholesterolemia (Boyle etc., " Supra ").
The medicine that is used to control type ii diabetes at present is nothing more than two types chemical compound: biguanides and sulfonylurea.Biguanides as first good fortune ketone, can bring out lactic acidosis through being proved it in U.S.'s use.Sulfonylurea as tolbutamide and glibenclamide, mainly is synthetic by stimulating insulin secretion, improve effect and the glucose in inhibition liver of insulin in some target tissue, reduces the glucose level in the blood plasma.
It is reported that normal individual replenishes serum lipid concentration, insulin and the insulin binding (Anderson, ClinPhysiol.Biochem., 4:31-41,1986) that chromium can improve glucose tolerance, comprise the high density lipoprotein cholesterol.Replenish three prices,, can increase the danger of adult diabetes mellitus and cardiovascular disease as chromium trichloride.
Known chromium is the insulin required cofactor that plays a role.It combines with insulin, and strengthen insulin many, perhaps be whole effects (Boyle etc., " Supra ".These effects include but not limited to regulate carbohydrate and lipid metabolism (" Present Knowledge inNutrition " supra, P573-577).
It is not useful especially introducing inorganic chromium chemical compound itself in individuality.Chromium must be converted into organic complex in vivo or must just can be utilized as bioactive molecule.In the organic chromium of being taken in, have only 0.5% by health absorption (" Recommended Daily Allowances " the 9th revised edition, national academy of sciences, the 160th page, 1980).Have only 1-2% to be absorbed in most of chromium compound by health.
United States Patent (USP) 4,315,927 disclose if give administration with selected essential metal as the complex compound of exogenous synthetic pyridine carboxylic acid, and these essential metals need not and other metal competition, just can directly absorb in the system of entering.A kind of compositions of this patent record and method are used for replenishing essential metal at human diet's selectivity, also are used to promote the absorption of enterocyte to these metals.These complex safety, cheapness have biological adaptability, and are easy to preparation.The essential metal complex compound of these exogenous synthetic pyridine carboxylic acids (pyridine-2-carboxylic acids) has following structural formula:
Wherein M represents metal cation, and n equals cationic quantivalence, and for example, if M is Cr and η=3, then this chemical compound is three chromium picolinates.The pyridine carboxylic acid salt of other chromium also comprises M=Cr
+ 3And n=2 (two chromium picolinates) or n=1 (single chromium picolinate).
U.S.'s " intake every day of recommendation " (RDA) regulation chromium is the 50-200 milligram.United States Patent (USP) 5,087,623 disclose in adult diabetes mellitus's treatment, and the dosage scope of three chromium picolinates is 50 to 500 milligrams.Compare with matched group, the chromium of using 200 milligram of three chromium picolinate form has caused the slight reduction of glycosylated hemoglobin, but this reduction has the significance meaning from statistical significance, and glycosylated hemoglobin is index of long-term blood sugar level control, is the accurate indication of blood sugar level.In normal individual, the glycosylated hemoglobin level is below 6%; And this value is brought up to 9-12% in diabetics.Therefore reduce a little to having arrived this value although observe, what reach after treating with chromium 10.4% still drops in the diabetes scope.Can not think relevant so blood glucose is reduced to this level with therapy.
Therefore, people need a kind of safe, effective, cheap compositions, and significantly blood sugar lowering concentration is to acceptable value.The present invention has satisfied this needs.
The present invention's general introduction
We find that unexpectedly if three chromium picolinates can significantly be lowered into the blood sugar level of people's diabetes mellitus type according to the dosed administration higher than RDA.
The present invention has improved the too high blood glucose of a kind of people of reduction and has made serum level of glucose keep stable method, and this method is to use about 1.000 to 10.000 milligrams chromium every day to the people where necessary, in synthetic three chromium picolinates.Preferably, the chromium amount of application is about 1.000 to 5.000 milligrams of every day, in synthetic three chromium picolinates.Three chromium picolinates combine more favourable with pharmaceutically acceptable carrier.According to the preferred embodiment of the present invention, three chromium picolinates are oral administration.The another kind of selection is that three chromium picolinates are through the parenteral administration.
Detailed description of the present invention
The present invention finds that chromium and the dosage of using the formation of three chromium picolinates as if the type ii diabetes patient are bigger than the RDA of the U.S., significantly the blood sugar lowering level.Its reduction degree is than obviously much bigger according to the administration of the desired chromium dose of RDA, and this illustrates that heavy dose of chromium picolinate can make blood sugar level stable.
Because chromium is the cofactor of potentiating insulin action, when people's expection is taken in the chromium of RDA range limit dosage when individuality, chromium will cause blood sugar level farthest to reduce in conjunction with all available insulins.On this viewpoint,,, the chromium dosage can not make blood glucose reduce effect above the RDA upper limit amount even being significantly higher than RDA because all available insulins make the chromium binding site saturated yet.Unexpectedly, with 1.000 milligrams every day dosage chromium with three chromium picolinate form administrations, weigh with the reduction of glycosylated hemoglobin, the significance degree that blood sugar level reduces is higher five times than cr intake upper limit every day (μ g every days 120) of proposed recommendations.On the contrary, give 200 milligrams of chromium with three chromium picolinate forms, its effect is unlike the height (example 1) that uses a kind of placebo.Similarly, show in the clinical experiment that University of Texas carried out that is positioned at the San Antonio city, take three chromium picolinates that contain 200 milligrams of chromium every day after, do not have hypoglycemic effect (Lee etc., " DiabetesCare (USA) " 17 (12): 1449-1452).Therefore the benefit with the treatment of three chromium picolinates is that obviously dosage relies on, and the dosage in so-called " nutrition scope " can not produce significant curative effect in the treatment type ii diabetes.
The synthetic method of chromium picolinate is stated from United States Patent (USP) 5,087, No. 623.In order to reduce the needs to insulin and/or diabetes medicament, also in order to reduce the risk factor of several keys relevant with type ii diabetes, it should be about 1.000 to 10.000 milligrams of every day that chromium is considered to the dosage range of three chromium picolinate form administrations.In preferred embodiment, dosage is about 1.000 to 5.000 milligrams of every day.
Although herein disclosed is with three chromium picolinate drug treatment type ii diabetes, use single chromium picolinate and two chromium picolinate administrations in case of necessity also within the scope of the present invention.
Chromium picolinate for oral use can be tablet, aqueous suspensions or oil suspension, dispersible powder or granule, emulsion, hard capsule or soft capsule, syrup or elixir.Composition for oral administration can be prepared according to any known method in the preparation of pharmaceutical compositions field, can contain one or more following ingredients in the said composition: sweeting agent, correctives, coloring agent and antiseptic.Sweeting agent and correctives can improve the mouthfeel of preparation.To contain the tablet of three chromium picolinates and the nontoxic pharmaceutically acceptable preparation tablets that is applicable to is acceptable in mixed with excipients.This excipient comprises inert diluent, as calcium carbonate, sodium carbonate, lactose, calcium phosphate or sodium phosphate; Granulating agent and disintegrating agent are as corn starch or algin; Binding agent is as starch, gelatin or arabic gum; And lubricant, as magnesium stearate, stearic acid or Pulvis Talci.Tablet can be without the also available already known processes coating of coating, to postpone disintegrate and the absorption in gastrointestinal tract, so that produce the long-acting slow-release effect.For example, use a kind of time-delay material,, or mix with a kind of wax as independent glyceryl monostearate or distearin.
Oral formulations also can be made into hard capsule, active component is wherein mixed with a kind of inert solid diluent, for example calcium carbonate, calcium phosphate or Kaolin, or make soft capsule, active component is wherein mixed with water or a kind of oil medium, as Oleum Arachidis hypogaeae semen, liquid paraffin or olive oil.
In the aqueous suspensions, the mixed with excipients of three pyridine carboxylic acid chromic compounds of the present invention and the preparation of suitable water suspension.This excipient comprises suspending agent, dispersant or wetting agent, one or more antiseptic, one or more coloring agent, one or more correctivess and one or more sweeting agents, as sucrose or glucide.
The preparation oil suspension can be suspended in active component in one vegetable oil, as Oleum Arachidis hypogaeae semen, olive oil, Oleum sesami or Oleum Cocois, or in a kind of mineral oil, as liquid paraffin.Can contain a kind of thickening agent in the oil suspension, as Cera Flava, hard paraffin or spermol.Add above-mentioned sweeting agent and correctives and can make the good oral formulations of mouthfeel.These compositionss are passed through to add a kind of antioxidant, as ascorbic acid, and anticorrosion.Dispersible powder of the present invention and granule are applicable to the preparation aqueous suspensions, promptly by adding entry, active component are mixed with a kind of dispersant or wetting agent, a kind of suspending agent and one or more antiseptic.Also can contain other excipient, as sweeting agent, correctives and coloring agent.
Use sweeting agent to can be made into syrup and elixir such as glycerol, Sorbitol or sucrose.These preparations also can contain a kind of demulcent, a kind of antiseptic, a kind of correctives or a kind of coloring agent.
The parenteral preparation of three chromium picolinates can be the form of aseptic injection, as aseptic injectable aqueous suspensions or oil suspension.Use suitable dispersant or wetting agent and suspending agent, can prepare this suspension according to methods known in the art.Aseptic injection also can be nontoxic pharmaceutically acceptable diluent or aseptic injectable solution or the suspension in the solvent, as 1,3 butylene glycol solution.The suitable dilution agent comprises, for example water, Ringer's mixture and isoosmotic sodium chloride solution.Can according to a conventional method aseptic miscella be used as solvent or suspension media in addition.For this reason, any non-irritating miscella be can use, synthetic monoglyceride or double glyceride comprised.Can be used for the preparation of injection in addition equally such as oleic fatty acid.
This pharmaceutical composition also can be the form of emulsion oil-in-water.Oil phase can be such as the vegetable oil of olive oil or Oleum Arachidis hypogaeae semen, such as the mineral oil of liquid paraffin, or its mixture.The emulsifying agent that is suitable for comprises the natural gum of natural origin, as Radix Acaciae senegalis and gum tragacanth, the phospholipid of natural origin, as soybean lecithin, ester or partial ester from fatty acid and hexitan, as dehydrated sorbitol mono-fatty acid ester, and the polycondensation product of these partial esters and oxirane, as the polyoxyethylene sorbitan monoleate.Also can contain sweeting agent and correctives in the emulsion.
Can change according to curee and concrete the different of administering mode in conjunction with the amount of three chromium picolinates that form single dosage form with support material.
Heavy dose of three chromium picolinates are seen following embodiment to the clinical efficacy experiment of type ii diabetes.
Embodiment 1
Heavy dose of three chromium picolinate therapies
180 type ii diabetes patients are carried out at random double blinding clinical experiment.Oral chromium picolinate patient's every day of/3rd contains 1,000 milligram of chromium (two 500 milligrams capsules); / 3rd oral 200 milligrams of chromium; 1/3rd use placebo.Took four months by above-mentioned dosage.This experiment begins and after two months, four months, detects latter two hour and measures fasting and after meal glucose level finishing glucose tolerance.Also measure the glycosylated hemoglobin level by standard method.The glycosylated hemoglobin level of taking the patient of three chromium picolinates that contain 1000 milligrams of chromium has on average reduced by 30%, and fasting and glucose level after meal reduce the spoke degree near (being respectively 28% and 27%).The glycosylated hemoglobin of diabetics reduced by 30% with the glycosylated hemoglobin value of about 6-8 be corresponding to, this is lower than most of glycosuria patients' 9-12 scope.On the contrary, only take 200 milligrams group every day and compare with the group of taking placebo, the reduction of these parameters does not have statistical remarkable meaning.
The above-mentioned explanation that the present invention carried out only be the invention provides help for understanding.To change of the present invention, comprise at present known and improved thereafter all be equal to replacement and all should be considered to drop within the scope of the invention, the scope of the invention is only limited by the appended claim in back.
Claims (15)
- One kind to reduce people's blood glucose too high and make serum level of glucose keep stable method, this method is included in uses synthetic three chromium picolinates that contain 1,000 to 10,000 milligram of chromium approximately in case of necessity every day to the people.
- 2. the method for claim 1, this method comprise uses synthetic three chromium picolinates that contain 1,000 to 5,000 milligram of chromium approximately every day.
- 3. the process of claim 1 wherein that described three chromium picolinates are present in the pharmaceutically acceptable carrier.
- 4. the method for claim 3, wherein said three chromium picolinate oral administration administrations.
- 5. the method for claim 3, wherein said three chromium picolinates through parenteral by way of administration.
- Synthetic three chromium picolinates of 6 unit dose modes, each dosage contains 1,000 to 10,000 milligram of chromium approximately, and it is too high and/or make serum level of glucose keep stable to be used for treating where necessary people's blood glucose.
- 7. three chromium picolinates of claim 6, wherein each dosage contains 1,000 to 5,000 milligram of chromium approximately.
- 8. claim 6 or 7 three chromium picolinates exist with a kind of dosage form of oral administration that is applicable to.
- 9. claim 6 or 7 three chromium picolinates exist with a kind of dosage form of parenteral that is applicable to.
- 10. claim 6 or 7 three chromium picolinates are present in a kind of pharmaceutically acceptable carrier.
- 11. the purposes of synthetic three chromium picolinates (each dosage contains 1 approximately, 000-10,000 milligram of chromium) of unit dose mode is used to prepare that to treat people's blood glucose where necessary too high and/or make serum level of glucose keep stable medicine.
- 12. the purposes of claim 11, wherein each dosage contains 1,000 to 5,000 milligram of chromium approximately.
- 13. the purposes of claim 11 or 12, wherein said three chromium picolinates exist with a kind of dosage form of oral administration that is applicable to.
- 14. the purposes of claim 11 or 12, wherein said three chromium picolinates exist with a kind of dosage form of parenteral that is applicable to.
- 15. the purposes of claim 11 or 12, wherein said three chromium picolinates are present in a kind of pharmaceutically acceptable carrier.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 96195218 CN1189776A (en) | 1995-05-12 | 1996-05-08 | High-dose chromic tripicolinate for the treatment of type II diabetes |
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US08/440,362 | 1995-05-12 | ||
| CN 96195218 CN1189776A (en) | 1995-05-12 | 1996-05-08 | High-dose chromic tripicolinate for the treatment of type II diabetes |
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| CN1189776A true CN1189776A (en) | 1998-08-05 |
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| Application Number | Title | Priority Date | Filing Date |
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| CN 96195218 Pending CN1189776A (en) | 1995-05-12 | 1996-05-08 | High-dose chromic tripicolinate for the treatment of type II diabetes |
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN100457122C (en) * | 2002-05-14 | 2009-02-04 | 尼普洛株式会社 | Medicine for prevention of and treatment for amyloidosis |
| CN102641280A (en) * | 2012-04-23 | 2012-08-22 | 重庆康刻尔制药有限公司 | Pioglitazone hydrochloride and glimepiride combination medicine, tablet and application thereof |
-
1996
- 1996-05-08 CN CN 96195218 patent/CN1189776A/en active Pending
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN100457122C (en) * | 2002-05-14 | 2009-02-04 | 尼普洛株式会社 | Medicine for prevention of and treatment for amyloidosis |
| CN102641280A (en) * | 2012-04-23 | 2012-08-22 | 重庆康刻尔制药有限公司 | Pioglitazone hydrochloride and glimepiride combination medicine, tablet and application thereof |
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