US3452144A - Method for treatment of congestive heart failure with coenzyme qn - Google Patents
Method for treatment of congestive heart failure with coenzyme qn Download PDFInfo
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/12—Ketones
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- This invention relates to a method for treatment of congestive heart failure which comprises administering ubiquinone of the formula H300 CH3 wherein n is an integer from 7 to inclusive, to a sufferer from the disease.
- ubiquinone is also referred to as ubiquinone 5n wherein n has the same meaning as in the above formula.
- Ubiquinone 5n is also designatable as coenzyme Qn.
- Congestive heart failure is one of the most important and common disorders of heart functions, and is caused by poor contraction of the heart due to various etiologies.
- Congestive heart failure has reference to such conditions that poor contraction is caused due to these etiologies, entailing insufficient blood output to each organ and tissue of the body, including congestion occurring posteriorly of the heart. Therefore, cardiac enlargement, dyspnea and edema are clinically observed as major symptoms of congestive heart failure.
- digitalis has mainly been used in the treatment of congestive heart failure.
- intoxication due to, for example, administration of excessive amount of digitalis has often occurred.
- xanthine derivatives have been employed for treating congestive heart failure, which are effective in the dilation of the coronary artery and to increase cardiac output, and also as diuretic; and these derivatives have mainly been used together with digitalis in the treatment of lung congestion. But thorough going caution must be paid in the treatment of congestive heart failure with such xanthine derivatives, since they increase the oxygen consumption of the heart muscle as side effect, whereby symptoms of congestive heart failure are often exacerbated.
- diuretics When congestive heart failure cannot be satisfactorily cured or improved by administration of digitalis alone or when digitalis intoxication is apt to be caused, diuretics have often been used as an auxiliary agent of digitalis, in addition to the above-mentioned xanthine derivatives, though they do not act directly on the heart muscle. Typical examples thereof are mentioned below:
- Thiazides These are inhibitors of carbonic anhydrase and exhibit diuretic action due to their accelerative effect of excretion of sodium and chlorine, but they often cause gastrointestinal disorder or eruption. Moreover, as they cause hypo-potassiemia due to their action of excretion of potassium, digitalis intoxication is frequently to be expected.
- Organic mercury preparations They inhibit succinic dehydrogenase and restrain reabsorption of sodium and chlorine to give a diuretic effect, but they are contraindicated for those patients who have renal disturbance.
- diuretic action is effected by administra tion of the organic mercury preparations, patients are sensitive to digitalis intoxication, and conversely when diuretic action is not effected, patients are sensitive to mercurial accumulation.
- Acetazolamides These are inhibitors of carbonic anhydrase and show diuretic effect by inhibiting reabsorption of sodium, but there are observed such side effects as lassitude, drowsiness and paresthesia.
- Anti-aldosterones These have been used as diuretics since aldosterones are considered to be a causing factor of edema, but they are inferior in diuretic effect to the above-mentioned medicines.
- Adrenal cortical hormones-They have been used as a last alternative only in a case when the above-mentioned medicines are not effective, because of their rather strong side effects.
- diuretics have widely been used in the treatment of congestive heart failure, but such use is bound up with the fatal defect that it is very difficult to make a proper administration, mainly due to their strong side effects.
- the desideratum has now been realized by the method of the present invention which comprises administering ubiquinone 5n of the formula CHaO CI-IaO wherein n is an integer of 7 to 10 inclusive, to a sufferer from the congestive heart failure.
- the principal object of this invention is to provide a method for the treatment of congestive heart failure, and this object is realized by administering ubiquinone to a sufferer from the disease.
- Ubiquinone is also sometimes designated coenzyme Q and is one of the coenzymes which is present in animal and plant organs, and in microorganisms such as yeast, especially in the mitochondria of the cells and comprises such multiple homologues as ubiquinone 5, ubiquinone l0, ubiquinone ubiquinone 35, ubiquinone 40, ubiquinone 45, ubiquinone 50, etc., according to the number of units in the isoprene chain. Therefore, ubiquinone 5n can be isolated from the above-mentioned sources. Ubiquinone 5n can also be prepared advantageously by utilizing the process described in Japanese Patent Publication Nos. 1,877/1955 and 10,169/1957.
- ubiquinone 35 In the present invention, ubiquinone 35, ubiquinone 40, ubiquinone 45 and ubiquinone 50 are used singly or in combination. Among them, ubiquinone 35 is practically used.
- the acute toxicity of ubiquinone 35 is LD :4000 milligrams per kilogram when administered intraperitoneally to mice. Toxic manifestations are not observed with daily intraperitoneal injection of 10, and 50 milligrams per kilogram, respectively, in rats for 30 days and no changes are observed histologically in the pituitary, thyroid, thymus, heart, lungs, liver, adrenals, spleen, kidneys or testes.
- the dose of ubiquinone in the method of this invention varies depending upon the severity of the congestive heart failure and the administration method.
- the daily dose for an adult is generally about 0.6 to 4 0 milligrams per kilogram of body weight in oral administration, and about 30 to about 2,000 milligrams per day in oral administration calculated on the body weight of the adult as 50 kilograms.
- the daily intravenous administration dose for an adult of ubiquinone is about 0.1 to about 20 milligrams per kilogram of body weight.
- ubiquinone by injection, especially intravenous injection, for realizing the object of the present invention.
- ubiquinone can be administered as it is or in a composition consisting of the ubiquinone and a pharmaccutically acceptable liquid or solid carrier which is not incompatible with ubiquinone.
- the composition can take the form of tablets, powder, granule, capsules, injection or suspension.
- the solid carrier which may be admixed with ubiquinone, can be, for example, cornstarch, lactose, talc, stearic acid, magnesium stearate, gums, or the like.
- the liquid carrier for injection or suspension can be, for example, water, vegetable oils, detergents, surface active agents, etc.
- An injection composition containing 10 milligrams of ubiquinone 35, 100 milligrams of surface active agent (ethylene oxide adduct of hydrogenated castor oil), 10 milligrams of benzyl alcohol, 9 milligrams of sodium chloride, and distilled water in an amount to make the whole amount 1 milliliter.
- surface active agent ethylene oxide adduct of hydrogenated castor oil
- benzyl alcohol ethylene oxide adduct of hydrogenated castor oil
- 9 milligrams of sodium chloride distilled water in an amount to make the whole amount 1 milliliter.
- Vial injection composition containing 50 milligrams of ubiquinone 50, 500 milligrams of polyethylene oxide sorbitan monoleate, 50 milligrams of benzyl alcohol, 45 milligrams of sodium chloride and distilled water in an amount to make the whole amount 5 milliliters.
- Vial injection compositions containing 1 00 milligrams of ubiquinone 35, 1,000 milligrams of surface active agent (ethylene oxide adduct of hydrogenated castor oil), 100 milligrams of benzyl alcohol, milligrams of sodium chloride, and distilled water in an amount to make the whole amount 10 milliliters.
- surface active agent ethylene oxide adduct of hydrogenated castor oil
- benzyl alcohol ethylene oxide adduct of hydrogenated castor oil
- milligrams of sodium chloride milligrams of sodium chloride
- Ubiquinone 35 was intravenously administered (50 milligrams daily) to the in-patients as an aqueous solution prepared by dissolving 100 milligrams of ubiquinone 35 in 10 milliliters of water, for 1 to 5 weeks depending upon the severity of the individual congestive heart failure.
- ubiquinone 35 was administered together with digitalis preparation; in some cases, ubiquinone 35 in place of digitalis administration was exclusively used with in-patients, and in cases where congestive heart failure was observed with digitalism, only ubiquinone 35 was administered.
- the method of the present invention is remarkably effective for the treatment of congestive heart failure, especially in improvement of TABLE L-OASE REPORTS TREATED WITH OOENZYME Q Com- Daily Durabined Symptoms and Case dosage Method of admintion use of signs before Eiiectiveness after Side 0.
- Age Sex Diagnoses (mg) istration (days) digitalis treatment treatment effects Judgment 1 17 M Mitral steno in- 50 Intravenous in- Dys nea, moist Dyspnea. dis- None Good.
- a method for the treatment of congestive heart 3.
- a method according to claim 1 which comprises ad-.
- a method according to claim 1 which comprises parenterally administering to an adult human a daily dose of from about 0.1 to about 20 milligrams, per kilogram of body weight, of ubiquinone of said formula.
- parenteral administration is by intravenous injection.
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Description
United States Patent METHOD FOR TREATMENT OF CONGESTIVE HEART FAILURE WITH COENZYME Qn Yuichi Yamamura and Taro Ishiyama, Osaka, Japan, as-
siguors to Takeda Chemical Industries, Ltd., Gsaka, Ja an N5 Drawing. Filed Mar. 27, 1967, Ser. No. 625,976 Claims priority, application Japan, Mar. 26, 1966, 41/ 18,875 Int. Cl. A61k 27/00 U.S. Cl. 424-331 8 Claims ABSTRACT OF THE DISCLOSURE Congestive heart failure is successfully treated with the aid of ubiquinone 5n (coenzyme Qn), 11:7 to 10, melusive.
This invention relates to a method for treatment of congestive heart failure which comprises administering ubiquinone of the formula H300 CH3 wherein n is an integer from 7 to inclusive, to a sufferer from the disease. Hereinafter in this specification ubiquinone is also referred to as ubiquinone 5n wherein n has the same meaning as in the above formula. Ubiquinone 5n is also designatable as coenzyme Qn.
Congestive heart failure is one of the most important and common disorders of heart functions, and is caused by poor contraction of the heart due to various etiologies.
Among the various etiologies, there are primarily a mechanical one which includes outflow load and inflow load and, secondarily, heart muscle damage itself.
Congestive heart failure has reference to such conditions that poor contraction is caused due to these etiologies, entailing insufficient blood output to each organ and tissue of the body, including congestion occurring posteriorly of the heart. Therefore, cardiac enlargement, dyspnea and edema are clinically observed as major symptoms of congestive heart failure.
Heretofore, digitalis has mainly been used in the treatment of congestive heart failure. In the treatment of congestive heart failure employing digitalis, however, intoxication due to, for example, administration of excessive amount of digitalis, has often occurred.
It is necessary to maintain a concentration of electrolyte, especially potassium, at a desired level, and it is often necessary to supply potassium due to inappropriate concentration of the electrolyte. Recently, it has been proposed to employ pure glycoside in place of powder of leaves of digitalis for attaining a constant activity, but the use of the pure glycoside tends to cause an increase in instances of intoxication. This fact is supported by an Patented June 24, 1969 increase in the ratio of effective dose to toxic dose in the cases of aged patients, serious heart diseases, heart muscle damage, cor pulmonale, renal disease, dysthyreosis and liver function disturbance.
In addition to digitalis, xanthine derivatives have been employed for treating congestive heart failure, which are effective in the dilation of the coronary artery and to increase cardiac output, and also as diuretic; and these derivatives have mainly been used together with digitalis in the treatment of lung congestion. But thorough going caution must be paid in the treatment of congestive heart failure with such xanthine derivatives, since they increase the oxygen consumption of the heart muscle as side effect, whereby symptoms of congestive heart failure are often exacerbated.
When congestive heart failure cannot be satisfactorily cured or improved by administration of digitalis alone or when digitalis intoxication is apt to be caused, diuretics have often been used as an auxiliary agent of digitalis, in addition to the above-mentioned xanthine derivatives, though they do not act directly on the heart muscle. Typical examples thereof are mentioned below:
Thiazides-These are inhibitors of carbonic anhydrase and exhibit diuretic action due to their accelerative effect of excretion of sodium and chlorine, but they often cause gastrointestinal disorder or eruption. Moreover, as they cause hypo-potassiemia due to their action of excretion of potassium, digitalis intoxication is frequently to be expected.
Organic mercury preparations.They inhibit succinic dehydrogenase and restrain reabsorption of sodium and chlorine to give a diuretic effect, but they are contraindicated for those patients who have renal disturbance. When excessive diuretic action is effected by administra tion of the organic mercury preparations, patients are sensitive to digitalis intoxication, and conversely when diuretic action is not effected, patients are sensitive to mercurial accumulation.
Acetazolamides.These are inhibitors of carbonic anhydrase and show diuretic effect by inhibiting reabsorption of sodium, but there are observed such side effects as lassitude, drowsiness and paresthesia.
Anti-aldosterones.These have been used as diuretics since aldosterones are considered to be a causing factor of edema, but they are inferior in diuretic effect to the above-mentioned medicines.
Adrenal cortical hormones-They have been used as a last alternative only in a case when the above-mentioned medicines are not effective, because of their rather strong side effects.
As mentioned above, diuretics have widely been used in the treatment of congestive heart failure, but such use is bound up with the fatal defect that it is very difficult to make a proper administration, mainly due to their strong side effects.
The foregoing illustrates generally the hitherto-known methods for treatment of congestive heart failure. The hitherto-known methods, however, are not completely effective for such treatment.
Especially, among the hitherto-known medicines for the treatment of congestive heart failure, only digitalis and xanthine derivatives act directly on the muscle of the heart. Moreover, in view of the undesirable side effects of digitalis and xanthine derivatives as mentioned above, it has been a desideratum in the art to provide effective and low toxic medicine for the treatment of congestive heart failure.
The desideratum has now been realized by the method of the present invention which comprises administering ubiquinone 5n of the formula CHaO CI-IaO wherein n is an integer of 7 to 10 inclusive, to a sufferer from the congestive heart failure.
The principal object of this invention is to provide a method for the treatment of congestive heart failure, and this object is realized by administering ubiquinone to a sufferer from the disease.
Ubiquinone is also sometimes designated coenzyme Q and is one of the coenzymes which is present in animal and plant organs, and in microorganisms such as yeast, especially in the mitochondria of the cells and comprises such multiple homologues as ubiquinone 5, ubiquinone l0, ubiquinone ubiquinone 35, ubiquinone 40, ubiquinone 45, ubiquinone 50, etc., according to the number of units in the isoprene chain. Therefore, ubiquinone 5n can be isolated from the above-mentioned sources. Ubiquinone 5n can also be prepared advantageously by utilizing the process described in Japanese Patent Publication Nos. 1,877/1955 and 10,169/1957.
In the present invention, ubiquinone 35, ubiquinone 40, ubiquinone 45 and ubiquinone 50 are used singly or in combination. Among them, ubiquinone 35 is practically used.
The acute toxicity of ubiquinone 35 is LD :4000 milligrams per kilogram when administered intraperitoneally to mice. Toxic manifestations are not observed with daily intraperitoneal injection of 10, and 50 milligrams per kilogram, respectively, in rats for 30 days and no changes are observed histologically in the pituitary, thyroid, thymus, heart, lungs, liver, adrenals, spleen, kidneys or testes.
The dose of ubiquinone in the method of this invention varies depending upon the severity of the congestive heart failure and the administration method. However, the daily dose for an adult is generally about 0.6 to 4 0 milligrams per kilogram of body weight in oral administration, and about 30 to about 2,000 milligrams per day in oral administration calculated on the body weight of the adult as 50 kilograms. The daily intravenous administration dose for an adult of ubiquinone is about 0.1 to about 20 milligrams per kilogram of body weight. When ubiquinone is administered in combination with any other drugs, the above-mentioned doses may be suitably changed.
In the present invention, it is preferable to administer ubiquinone by injection, especially intravenous injection, for realizing the object of the present invention.
According to the method of this invention, ubiquinone can be administered as it is or in a composition consisting of the ubiquinone and a pharmaccutically acceptable liquid or solid carrier which is not incompatible with ubiquinone. The composition can take the form of tablets, powder, granule, capsules, injection or suspension. The solid carrier, which may be admixed with ubiquinone, can be, for example, cornstarch, lactose, talc, stearic acid, magnesium stearate, gums, or the like. The liquid carrier for injection or suspension can be, for example, water, vegetable oils, detergents, surface active agents, etc.
The following illustrative examples of preparations containing ubiquinone as an active ingredient are given:
(1) A capsule containing 5.0 milligrams of ubiquinone 35 and 77.0 milligrams of granular lactose.
(2) A capsule containing 20.0 milligrams of ubiquinone 35 and 230.0 milligrams of granular lactose.
(3) A capsule containing 10.0 milligrams of ubiquinone 45 and 140.0 milligrams of granular lactose.
(4) A capsule containing 20.0 milligrams of ubiquinone 35 and 230.0 milligrams of granular lactose.
(5) An injection composition containing 10 milligrams of ubiquinone 35, 100 milligrams of surface active agent (ethylene oxide adduct of hydrogenated castor oil), 10 milligrams of benzyl alcohol, 9 milligrams of sodium chloride, and distilled water in an amount to make the whole amount 1 milliliter.
(6) An injection composition containing 10 milli grams of ubiquinone 45, 100 milligrams of surface active agent (ethylene oxide adduct of hydrogenated castor oil), 10 milligrams of benzyl alcohol, 9 milligrams of sodium chloride, and distilled water in an amount to make the whole amount 1 milliliter.
(7) Vial injection composition containing 50 milligrams of ubiquinone 50, 500 milligrams of polyethylene oxide sorbitan monoleate, 50 milligrams of benzyl alcohol, 45 milligrams of sodium chloride and distilled water in an amount to make the whole amount 5 milliliters.
(8) Vial injection compositions containing 1 00 milligrams of ubiquinone 35, 1,000 milligrams of surface active agent (ethylene oxide adduct of hydrogenated castor oil), 100 milligrams of benzyl alcohol, milligrams of sodium chloride, and distilled water in an amount to make the whole amount 10 milliliters.
(9) A capsule containing milligrams of ubiquinone 45 and vegetable oil.
(10) A capsule containing 100 milligrams of ubiquinone 40 and 250 milligrams of granular lactose.
(11) An intramuscular injection composition containing 50 milligrams of ubiquinone 35 in vegetable oil, in an amount to make the whole amout 1 milliliter.
Clinical evaluation for treatment of cardiovascular diseases (1) Material and method.-There were chosen 15 inpatients in the test who were suffering from congestive heart failure due to various kinds of cardiovascular diseases including 6 cases of valvular diseases, 4 cases of hypertensive heart disease, 4 cases of arteriosclerotic heart disease and one case of chronic cor-pulmonale.
Ubiquinone 35 was intravenously administered (50 milligrams daily) to the in-patients as an aqueous solution prepared by dissolving 100 milligrams of ubiquinone 35 in 10 milliliters of water, for 1 to 5 weeks depending upon the severity of the individual congestive heart failure.
In most cases, ubiquinone 35 was administered together with digitalis preparation; in some cases, ubiquinone 35 in place of digitalis administration was exclusively used with in-patients, and in cases where congestive heart failure was observed with digitalism, only ubiquinone 35 was administered.
(2) Result.-Results are shown in Table 1 and the summary thereof is shown in Table 2 where the effectiveness of ubiquinone 35 on congestive heart failure is evaluated with consideration of alleviation of dyspnea, reduction of hepatoma, increase of urine volume, etc.
(3) Side eifect.There was observed no side effect.
As is clearly shown in Table 2, the method of the present invention is remarkably effective for the treatment of congestive heart failure, especially in improvement of TABLE L-OASE REPORTS TREATED WITH OOENZYME Q Com- Daily Durabined Symptoms and Case dosage Method of admintion use of signs before Eiiectiveness after Side 0. Age Sex Diagnoses (mg) istration (days) digitalis treatment treatment effects Judgment 1 17 M Mitral steno in- 50 Intravenous in- Dys nea, moist Dyspnea. dis- None Good.
sufliciency with jection with ra es, 11 ve1 1 fb. appeared. aortic insuifiglucose (20%). felt, daily ciency. amount of urine 500 cc. 2 68 M Hypertensive Intravenous 15 Weakness, exer- Weakness, shortdo. Do.
heart disease. injection. tional shortenness of breath ing of breath, disap cared, liver 2 fb. felt. liver ecreased to 1 fb. 3 M Mitral stenosis.... 50 .do 8 Fit of dyspnea Fit of dyspnea ..-do... Excellent.
everyday, digidisappeared. talis intoxication. 4 44 F Mitral stone in- 50 do 10 Dys nea, moist Dys nea, moist ...do. D sufiiciency. ra es, liver 4 fb. ra es disapfelt, pretihial peared, liver 2 edema, oliguria, fb. felt, edema EC G: STv56 disappeared, depressed. urine amount increased, ECG: ST depression disappeared. 5 71 M Arterlosclerotic 50 -...do 7 Fit of dyspena Fit of dyspnea do N at efi heart disease. unchanged, t
digitalis, thiazide not effective. 6 M .do 50 do 20 Weakness, cough, Weakness disap- ...do Ex ll t,
liver swelling. peared, cough decreased, urine amount increased, cold feeling of legs disappeared. 7 52 M Chronic myo- 50 -..-.do 12 Cough, sputum, Cough, sputum, ..do. Do,
cardial infarcmoist rales, moist rales distion. daily amount of appeared, daily urine 600 cc. amount of urine 1,500 cc. 3 52 F Hypertensive 50 ----.do 35 Dyspnea, cough, Dyspnea dedo G heart disease; ECG: '1 wave creased, cough inverted. disappeared,
ECG: T inversion disappeared. 9 33 F Mitral stone in- 50 .d0 21 Dyspnea, liver 5 Dyspnea dedo E 11 sufiiciency. fb. elt. creased, bradycardia, liver 3 fb. felt, urine amount increased. 10 32 F Mitral insuflicien- 50 -..-.do 21 Dyspnea, heart Dyspnea disapdo cy. rate 120, moist peared, heart rales, liver 2 fb. rate 72, moist felt. rales disappeared, liver 0.5 fb. felt. 11 31 M Mitra1stenosis. 50 -...do 7 Exertional short- Shortness of -do G d,
enlng of breath, breath, edema edema. disappeared. 12..." 71 F Hypertensive 50 .do 28 Dyspnea, moist Dys nea, moist do D heart disease.- rales, ECG: ra es disapp- STVG depressed. peared, ECG: Tv6 upright. 13..-" 51 M Chronic cor-pul- 50 0 8 Dyspnea, edema.-- Dys nea, edema -do. Ex elle t,
monale due to disappeared. pulmonary tuberculosis. 14..." 77 F Hypertensive 50 .d0 10 Dyspnea Dyspnea disap- -do Good.
heart disease. peared. 15 54 M Arteriosclerotlc 50} ....do 8} Dyslpnea, moist Dys nea, moist .do. Excellent.
heart disease. 100 10 ra es, liver 2 fb. ral s disapfelt, daily eared, liver 2 amount of b. felt, daily urine 400 cc. amount of urine Criteria of judgments- Excellent: Cases whose symptoms and signs of congestive heart failure disappeared or im roved remarkably when Ooenzyme Q, is administered additlonally during dlgltaflstreatment, or when administered singly after interruption of the igitalis treatment. Good: Cases whose symptoms and signs are decreased. Not effective: Cases whose symptoms and signs are unchanged 0r worsened.
TABLE 2.SUMMARY OF THE EFFECTIVENESS OF COEN ZYME Q ON CONGESTIVE HEART FAILURE failure which comprises administering an effective amount of ubiqulnone 5n of the formula Un- 0 Excellent Good changed Total ll Valvular diseases 4 2 0 6 (EH3 CH@ Hypertecnlsive heart disease" 0 4 0 4 (1H3 't ios otic ear di s easefj 3 0 1 4 01330 (CH2OH=COH1),.H Chronic cor-pulmonale 1 0 0 1 I Total 8 6 1 15 0 wherein n is an integer from 7 to 10 inclusive, to a Having thus disclosed the present invention, what we sufferer from congestive heart failure. claim is: 2. A method according to claim 1 wherein n is 7.
1. A method for the treatment of congestive heart 3. A method according to claim 1 wherein n. is 8.
6. A method according to claim 1 which comprises ad-.
ministering orally to an adult human a daily dose of from 0.6 to 40 milligrams, per kilogram of body weight, of 5 ubiquinone of said formula. 1
7. A method according to claim 1 which comprises parenterally administering to an adult human a daily dose of from about 0.1 to about 20 milligrams, per kilogram of body weight, of ubiquinone of said formula.
8. A method according to claim 7 wherein the parenteral administration is by intravenous injection.
8 References Cited UNITED STATES PATENTS 12/1963 Grim 16758 5/1967 Umehara "167-55 OTHER REFERENCES Vitamins and Coenzyrnes, Wagner, A., et al., pp. 467- 468, 1964.
10 ALBERT T. MEYERS, Primary Examiner.
H. M. ELLIS, Assistant Examiner.
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP1887566 | 1966-03-26 |
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| Publication Number | Publication Date |
|---|---|
| US3452144A true US3452144A (en) | 1969-06-24 |
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| US625976A Expired - Lifetime US3452144A (en) | 1966-03-26 | 1967-03-27 | Method for treatment of congestive heart failure with coenzyme qn |
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Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0023349A2 (en) * | 1979-07-25 | 1981-02-04 | Eisai Co., Ltd. | Ubidecarenone composition enhancing the absorption |
| EP0118132A2 (en) * | 1983-03-08 | 1984-09-12 | Eisai Co., Ltd. | A remedial or prophylactic agent for the treatment of seizures |
| US4525350A (en) * | 1975-02-20 | 1985-06-25 | The New England Institute, Inc. | Methods of stimulating host defense system with coenzymes Q4 to Q.sub.1 |
| EP0196085A2 (en) * | 1985-03-28 | 1986-10-01 | Eisai Co., Ltd. | Composition containing ubidecarenone with promoted absorption |
| US6461593B1 (en) * | 1992-02-19 | 2002-10-08 | Biomedical And Clinical Research | Therapy with coenzyme Q10 to reduce subgingival microorganisms in patients with periodontal disease |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3113073A (en) * | 1961-03-06 | 1963-12-03 | Merck & Co Inc | Solutions of benzoquinone derivatives |
| US3317381A (en) * | 1965-10-04 | 1967-05-02 | Takeda Chemical Industries Ltd | Method for treating peptic ulcer |
-
1967
- 1967-03-27 US US625976A patent/US3452144A/en not_active Expired - Lifetime
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3113073A (en) * | 1961-03-06 | 1963-12-03 | Merck & Co Inc | Solutions of benzoquinone derivatives |
| US3317381A (en) * | 1965-10-04 | 1967-05-02 | Takeda Chemical Industries Ltd | Method for treating peptic ulcer |
Cited By (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4525350A (en) * | 1975-02-20 | 1985-06-25 | The New England Institute, Inc. | Methods of stimulating host defense system with coenzymes Q4 to Q.sub.1 |
| EP0023349A2 (en) * | 1979-07-25 | 1981-02-04 | Eisai Co., Ltd. | Ubidecarenone composition enhancing the absorption |
| EP0023349A3 (en) * | 1979-07-25 | 1982-03-10 | Eisai Co., Ltd. | Ubidecarenone composition enhancing the absorption |
| EP0118132A2 (en) * | 1983-03-08 | 1984-09-12 | Eisai Co., Ltd. | A remedial or prophylactic agent for the treatment of seizures |
| EP0118132A3 (en) * | 1983-03-08 | 1985-11-06 | Eisai Co., Ltd. | A remedial or prophylactic agent for the treatment of seizures |
| EP0196085A2 (en) * | 1985-03-28 | 1986-10-01 | Eisai Co., Ltd. | Composition containing ubidecarenone with promoted absorption |
| EP0196085A3 (en) * | 1985-03-28 | 1987-08-12 | Eisai Co., Ltd. | Composition containing ubidecarenone with promoted absorption |
| US6461593B1 (en) * | 1992-02-19 | 2002-10-08 | Biomedical And Clinical Research | Therapy with coenzyme Q10 to reduce subgingival microorganisms in patients with periodontal disease |
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