United States Patent (19) 11) Patent Number: 4,619,829 Motschan 45 Date of Patent: Oct. 28, 1986

4,386,072 5/1983 Horrobin et al...... 424/127

54 UTILIZATION OF ASINGLEVITAMINORA COMBINATION OF WARIOUS VTAMNS 4,387,093 6/1983 Lysaght ...... 424/1.31 4,439,454 3/1984 Riva ...... 424/329 76 Inventor: Georges Motschan, Schönbeinstrasse 21, 4056 Basel, Switzerland OTHER PUBLICATIONS 21 Appl. No.: 631,555 Chem. Abst., 72, 99038q, (1970)-Guglielmi et al. Chem. Abst, 74,73981h, (1971)-Fukui. 22, PCT Filed: Nov. 16, 1983 Chem Abst, 76,21283d, (1972)-Alter et al. 86 PCT No.: PCT/CH83/00127 Chem. Abst, 76, 70679(w), (1972)-Kurmaeva et al. Chem. Abst., 81, 131090z, (1974)-Nash. S371 Date: Jul. 13, 1984 Chem. Abst., 90, 70869x, (1979)-Miskinite et al. S 102(e) Date: Jul. 13, 1984 Chem. Abst., 90, 145621w, (1979)-Wilkins et al. "The Healing Factor'-Irwine Stone-1972-pp. 87 PCT Pub. No.: WO84/01899 108-112. PCT Pub. Date: May 24, 1984 Primary Examiner-Douglas W. Robinson 30 Foreign Application Priority Data Attorney, Agent, or Firm-Ostrolenk, Faber, Gerb & Nov. 16, 1982 CH Switzerland ...... 6682/82 Soffen 51) Int. Cl.' ...... A61K 31/525; A61K 33/42 57 ABSTRACT 52) U.S.C...... 424/128; 514/251; The invention refers to a new utilization of a unique 514/825; 514/904; 514/905 or a combination of various in the 58 Field of Search ...... 514/276, 251, 825, 904, long-term treatment and/or prevention of rheumatic 514/905; 424/128 diseases. 56) References Cited During a long-term treatment and/or prevention of U.S. PATENT DOCUMENTS rheumatic diseases, a unique vitamin or a combination 1,261,995 4/1918 Ampt ...... 424/355 of various vitamins is administered to a patient. 2,816,854 12/1957 Gross ...... 424/143 4,206,222 6/1980 Valetas ...... 424/279 9 Claims, No Drawings 4,619,829 1 2 It is of the utmost importance that an application in UTILIZATION OF A SINGLE VITAMEN OR A conformity with the invention is a long-term therapy, in COMBINATION OF WARIOUS VITAMNS conformity with the invention. The expression "long term therapy” ordinarily depends on the degree of the The present invention refers to a new utilization of a disease to be treated, the general state of health of the single or a combination of various vitamins in the long patient, his body weight and his age. The expert will term therapy and/or prophylaxis of rheumatic diseases easily find out how long the treatment has to last until and a method for a long-term therapy and/or prophy improvement or complete healing is achieved. If need laxis of rheumatic diseases. be, the daily administration of the active substance or of Rheumatic diseases are widespread illnesses. In the 10 the combination of active substances can be interrupted USA alone about 30 million people suffer from arthritis, for a specific period of time, for instance 1 week or 1 vide TIME MAGAZINE nr. 33, page 41, of Aug. 16, month or longer and can subsequently be resumed at the 1982. In the "Bulletin on the Rheumatic Diseases', vol. same, an increased or a decreased rate. Depending on 32, nr. 1 (1982), page 1, published by the Arthritis Foun the specificity of the patient's individuality, it has been dation, 3400 Peachtree Road, N.E. Atlanta, Ga. 30326, 15 found, priority has to be given to a long-term therapy of well-known therapies of rheumatoid arthritis are de not less than 5 months, especially not less than 6 scribed. months, preferably 1 year, and better still not less than The active substances collectively denominated Vita 2 years. In some cases, it appears to be of the utmost mins are known, vide for example "Chemie Lexikon' advantage for the patient if the long-term treatment by Prof. Dr. Hermann Römpp, Franckh'sche Verlag 20 lasts for life. shandlung, Stuttgart. Special preference is to be given to the long-term, It is described in the literature that neither short-term regular, continuous, uninterrupted and daily applica administration of vitamins nor high-level doses and/or tion, in conformity with the invention, of an active so-called massive doses result in improvement in cases substance or a combination of active substances in con of rheumatoid arthritis; vide "Arthritis and Allied Con 25 formity with the invention, in order to achieve healing ditions. A Textbook of Rheumatology'. Editor: Joseph and/or stoppage and/or prevention (prophylaxis) of a Lee Hollander, M.D., Seventh Edition. Published (in rheumatic disease, especially of a polyarthritis in gen Europe) by Henry Kimpton, London, 1966, especially eral and of a primary chronical polyarthritis. chapter 37, "Diet and Vitamins in Rheumatoid Arthri Preferably the vitamin or vitamins belong to the tis', by Ronald Lamont-Havers, M.D. 30 vitamin-B-complex; regarding this term's definition the Completely surprisingly, it now was found that rheu above mentioned "Chemie Lexikon' for example serves matic diseases can very successfully be treated by ad as reference. ministration of at least one vitamin over a long period of The application of the vitamin or a combination of time, be it prophylactically, for improvement and/or vitamins can be, in conformity with the invention, con recovering. 35 bined and supplemented with a mineral and/or trace The present invention refers to a new application of a element and/or at least an additive, especially carriers, single or a combination of various vitamins in the long antioxidants, bacteriostats. term therapy and/or prophylaxis of rheumatic diseases, Following hereunder the specific newly applicable especially such of inflammatory and degenerative na compounds, in conformity with the invention, are de ture, which involve joints, muscles, tendines and other 40 scribed, their synonyms, their biological preliminary parts of the locomotive system. Examples of such dis stages (if any) and their chemical denominations: eases are the inflammations of joints, chronical polyar thritis, a primary chronical polyarthritis and a general VITAMINA arthritis, especially a chronical and/or acute arthritis. Synonyms: The word “Polyarthritis' has hereafter to be inter 45 preted as a collective expression for all possible forms of Axerophtol appearances of this disease(s) and its aetiology(ies), be it Antixerophtalmic vitamin rheumatoid arthritis, primary chronical polyarthritis, Antiinfectuous vitamin osteoarthritis or any of the more than 100 other forms Skin protecting vitamin and variations, symptoms and syndromes of this disease. 50 Growth vitamin Hereafter the supreme and collective expression polyar Biological preliminary stages: thritis will be used. a-6-y-Carotin The long-term therapy can be applied in any way; the Cryptoxanthin (3-Hydroxy-3-carotin) systemic, injection and the topical administrations are Echineon (4-oxo-f3-carotin) preferred. Above all, however, the most preferable is 55 Citroxanthin (Mutatochrome; (3-carotinoxide) the oral administration. The active substances acting as Myxoxanthin antirheumatic agents are administered orally and/or by Torularhodin injection in a dosage of about 0.25-2 mg/kg body Aphanin weight per day, preferably 0.5-1 mg/kg/per day, al Chemical Denominations: though higher or lower doses can be applied too and 60 easily determined by an expert, for example a physician. CH3 - In vitamin combinations, the quantities of the specific CH3 H vitamins can be varied. The dose can be administered as H C. C CH3CH3 C Sa S1S a single-dose or be dispensed over several part-doses. Cs-CsC C s1 Hr. HeH CH3 CH3 For the preferred oral administration the customary 65 2 H CH3 2 modes are to be taken into consideration, such as cap CH3 sules, lacquered tablets or tablets. The manufacture of such modes of administration can be the customary one. all-trans-3-carotin 4,619,829 3 4. -continued 21 2'/ 5 Sa | N NH2 N 3-pyridine carboxamide all-trans-vitamin A1 = all-trans-3,7-dimethyi-9-(2,6,6'- trimethyl-1'-cyclohexen-l'-yl)-2,4,6,8-nonatetraen-1-ol 10 VITAMIN B6 Synonyms: CH CH CH3 CH3 3 H 3 CNH C H C H CHCH2OH Adermin isSa C1 SSn c1 SS. c1 S.c1 Anti-acrodynic-factor CH3 15 Anti-dermatitis-factor Rat Pellagra Preventive Factor all-trans-vitamin A2 = 3',4'-Dehydrovitamin A1 Chemical Denominations:

CH2OH VITAMIN B1 20 Synonyms: Ho-1 CH2OH CH3-S Aneurine N Antineuritic vitamin 2-methyl-3-hydroxy-4,5-di(hydroxymethyl)-pyridine Anti-Beriberi-vitamin 25 Pyridoxole Beriberi Preventive Substance CHO Torulin Chemical Denomination HO 21 CH2OH 30 CH3-S N 2- -- N CH2-N CH3 2-methyl-3-hydroxy-4-formyl-5-hydroxymethyl-pyridine CH-ls NH2 Tason Pyridoxal N S CH2NH2 3-(4-amino-2-methylpyrimidyl-5-methyl)-4-methyl-5-6- 35 hydroxy-ethylthiazole Ho-21 CH2OH

CH3 S. N VITAMIN B2 2-methyl-3-hydroxy-4-aminomethyl-5-hydroxymethyl-pyridine Synonyms: 40 The group of the 3 active substances Pyridoxole, Pyri Lactoflavin doxal, Pyridoxamine, all of which have vitamin-B6 ef Chemical Denomination: fects, are gathered under the denomination Pyridoxine. 45 OHOHOH Synonyms: Filtrate factor (H----CH-OHH. H. H. N N Bios IIa CH3 Y c=o 50 Bios III Chick-anti-dermatitis-factor CH3 e NH Anti-gray (hair)-factor N c1 Chemical Denominations: O 6,7-dimethyl-9-(D-1'-ribityl)-isoalloxazin 55 SH: HOCH2-C-CHOH-CO-NH-CH2-CH2-COOH CH3 Synonyms: Nicotinamide 60 D(+)-ay-dihydroxy-6, (3-dimethylbutyryl-3'-alanin Nicotylamide Niacinamide SH: Vitamin PP HOCH2-C-CHOH-CO-NH-CH2-CH2-CH2OH CH3 Pellagra Preventive Factor 65 PP Factor Pantothenyl alcohol () Pellagra preventive factor Salts: Pantothenic calcium (Calcium-D-Pantothenate) Chemical Denomination: 4,619,829 5 6 N N Synonyms: NH-1 raS COOH Vitamin H V Bios II 5 N N 1. CH-NH-)-co-Nigh Bios Ib CH2 OH Coenzyme R CH2 Skin Factor W Antisebaceous vitamin COOH 10 N-4-((2-amino-4-hydroxy-6-pteridyl)methyl)-amino)benzo Chemical Denomination: yl)-glutamic acid NH-CH-CH2 / V VITAMIN B12 O=C S V / 15 Synonyms: NH-CH-h Erythrocine (CH2)4 Animal protein factor (APF) COOH Antipernicious Anaemia Factor 3,4-(2-ketoimidazolido)-2(a)-carboxylbutyl)-thiophan(A-Biotin) Extrinsic Factor (CASTLE) NH-co-ch-H, (H, CHN CH-co-NH. CH C C

NH-co-ch / N1 N-1 B N lic A N uCH-CH-CH-co-NH. a ch,)---, C N 6. CH CH / A N N-me N / CH3 NH-co-ch-c\ diC C Ce /Sc Yeh 1. 1 Nc4 3 / N N co-ch-ch, CH3 CH3 CH2-CH2-CO-NH2 ? SH: A N N1. CHN/ CH3 CH3-CH O- CH O N/2 No \-N-\ CH3 O OH C-C Ch? H HY N 1 HO-dH O So far, a considerable number of vitamin-B12-factors 55 (Cobalamins) have been isolated and represented. They differ from each other by distinct nucleous parts and show different biological activities. Vitamin B12 is ex tracted mainly from residues of cultures of Streptomyces griseus and similar organisms. FOLIC ACID 60 Synonyms: Synonyms: Pteroglutamic Acid Ascorbic acid Vitamin B Antiscorbutic acid Vitamin M 65 Antiscorbutic vitamin Eluate Factor (Liver) Antiscorbutine Lactobacillus casei factor Hexuronic acid Chemical Denomination: Chemical Denominations: 4,619,829

OH OH O O I C C C C O A. th O CHOH-CH2OH-uri 2 -A-So-H2 O No 1 S H. No CH-CHOH-CH2OH Ascorbic Acid is L-threo-2,3,4,5,6- = pentoxy-hexon-2-carbonic-acid 2,3-diketo-L-gulono-lactone lactone = L-threo-3-ketohexuronic acid-enole-lactone

VITAMIND min E is understood to be the a- or its ace Synonyms: tate, which possesses the greatest efficacy amongst all Calciferol 15 . Anti-Rachitis-Vitamin Chemical Denominations: Chemical Denominations: CH3 H2 CH3 CH3 CH3

HO H2 H2 CH 20 CH H O CH3 CH3 H H2 a-Tocopherol: 2,5,7,8-Tetramethyl-2-(4,8", 12'-trimethyl-dodecyl)- HO CH3 chroman-6-ol or 5,7,8-trimethyl-tocol 25 g-Tocopherol: 5,8-dimethyltocol H CH3 CH3 y-Tocopherol: 7,8-dimethyltocol H2 H 8-Tocopherol: 8-Monomethyltocol e-Tocopherol: 2-Farnesyl-2,5,8-tetramethylchroman-6-ol f Vitamin D2: -Tocopherol: 2-Farnesyl-2,5,7,8-tetramethylchroman-6-ol (Irradiated product of the ) m-Tocopherol: 2-Monomethyltocol 30

CH3 Hereunder are some exemplary preferred combina tions of active substances for the application in confor mity with the invention and the method in conformity with the invention are represented, emphasizing that the 35 present invention is not restricted to such combinations only. Their manufacture to be the usual one.

Vitamin D3: 1. Vitamin-B-complex factors. 40 Composition (Irradiated product of the 7,8-dehydro-cholesterol) Active Substances: the main factors of the vitamin-B- complex in pure form and in therapeutically adjusted relations to Apart from vitamins D2 and D3, which alone for quantities. themselves are applied therapeutically, a series of re Types: lated compounds have been detected, all of which to Tablets 45 Drops “forte' Ampoules gether with the former named vitamins comprise the per ml per Sirup per so-called group of vitamin-D. (20 tablet per ampoule Vitamin D1: Molecular compound of Vitamin D2 and drops) +) 5 ml (2 ml) lumisterol2 (irradiated product of ). None Vitamin B1 5 mg 15 mg 5 mg 10 mg existant in nature. Vitamin B2 2 mg 15 mg 2 mg 4 mg Vitamin D4: Irradiation product of 22,23-dihydroergos 50 Nicotinamide 20 mg 50 mg 20 mg 40 mg terol; Vitamin B6 2 mg 10 mg 2 mg 4 mg Calciumpantothenate --- 25 mg - - Vitamin D5: Irradiation product of 7-dehydrositosterol; Panthenol 3 mg - 3 mg 6 mg Vitamin D6: Irradiation product of 7-dehydrostigmas Biotin 0.25 mg 0.15 mg - 0.5 mg terol; Vitamin B12 4 Jug 10 pig - 8 ug Vitamin D7: Irradiation product of 7-dehydrocampost 55 ml drops contain 1.4 g carbohydrates, corresponding to 4.7 kilo calories, 1 tablet erol (isomer to 22,23-dihydroergosterol). (forte) 270 mg, corresp. to 1.1 kilo calories, and 5 ml sirup 4.02g, corresponding to 6.5 kilo calories. () this composition is denominated hereunder as "Combination I'. Synonyms: Tocopherol 60 Anti-dystrophy-vitamin 2. Vitamin-B-Complex together with Vitamin C (tablets, resp. with Vitamin C and Calcium (effervescent tablets). Anti-sterility-vitamin Composition Fertility-vitamin Per Vitamin Estands for the the whole group of Tocoph tablet Per efferve erols, which differ from each other by number and 65 (**) scent tablet position in the methyl groups on the hydroxychrome Vitamin B1 15 mg 15 mg ring, partly also by the presence of double compounds Vitamin B2 15 mg 15 mg within the phytyl side chain. Generally however vita Nicotinamide (PP-factor) 50 mg 50 mg 4,619,829 9 10 -continued CASE A 2. Vitamin-B-Complex together with Vitamin C (tablets, resp. with Female A was born Sept. 30, 1890, in St. Petersburg Vitamin C and Calcium (effervescent tablets). Composition (today Leningrad), Russia, of Russian-Finnish descent, Per 5 lives since 1924 in Zirich (Switzerland). Little is known tablet Per efferve- about her parents, brothers and sisters, as no contact (*) scent tablet with them exists since 1934. Person A does not remem Vitamin B6 10 mg 10 mg ber any more in 1982 what kind of illnesses had oc Calciumpantothenate 25 mg 25 mg curred in her faimily. VAn B12 0. . 0. 10 Person A enjoyed very good health until very old Vitamin C 500 mg 1000 mg age. In 1964 at the age of 74 she overcame an appendec Calcium carbonate - 156.25 mg tomy so striking lightly that the chief surgeon not only Calcium glycerophosphate - 327 mg released her from hospital only one week after the oper 1 Effervescent tablet contains 704 mg carbohydrates, corresponding to 2.9 kilo ation, but allowed her expressively to immediately de gcalories; NaCl). each When effervescent strict low-salt tablet regimen contains is besides applied about the adminstration230 mg Na (corr, of tabletsto abt. 0.6in- 15 part for holidays. At the outset of 1982, person A still steadof effervescent tablets is advisable. had all her own teeth. ("") This composition is denominated "Combination II" hereunder. Person A measures about 153 cm and is finely shaped. A non-smoker throughout her life, she was always a "good eater', carnivorous, drinking little alcohol,-an Polyvitamin Preparation 20 occasional glass of wine and during meals only. Her Combination weight in 1972 was was guessed to be about 47 kilos. It Per effer- must have been in 1972, ten years ago, when she started Verscent Per capsule to complain about "rheumatic pains' in her right shoul 12 Vitamins tablet Per tablet (x)kkak der and her right knee. Since 1948 widowed, she was 25 000 I.U. 25 000 I.U. 25 000 I.U. 25 very keen to walk daily about town, covering thus some Vitamin B 20 mg 20 mg 20 mg 10 to 12 kilometers per day. Attacks of pain in the right VitaminNicotinamide B2 505 mg 505 mg 505 Ingmg knee automaticallyt tical curtailedilled ththe extensionstensi off such Vitamin B6 10 10 mg 10 mg daily walks. The disease manifested itself slowly and Panthenol - - 10 mg insidiously only over years. iterate 11.6 mg 11.6 mg - 30 For a longer period of time-propably from 1973 Biotin (Vitamin H) 0.25 mg 0.25 mg 0.25 mg through 1975-see consulted her house-doctor. Subse Vitamin B12 5 pig 5 Jug 5 ug quently person A took in, on perscription of her physi Folic acid 1 mg 1 mg 1 mg cian, various NSAID-antirheumatics, such as Aspirin, Vitamin C 150 mg 150 mg 150 mg Irgapyrin, Butazolidin, Volaterene and many others. Vitamin ED 50010 I.U.mg 50010 mgI.U. 00010 I.U.mg 35 N o positiveiti resultslt were noted.ted. Wh en thine physicianhvsici started, in about 1975, to inject a substantial number of shots (exact figure not shown) directly into the knee

8 Minerals and Per effervescent trace elements tablet Per tablet Per capsule Calciun 262 mg CaC3H5 (OH)2PO4 129 mg Ca3 (PO4)2 435 mg CahPO4.2H2O Iron 12.5 mg Fe carbonic, sacc. 50 mg FeSO4.7H2O 10 mg Fe reduct. Magnesium 40 mg MgC3H5 (OH)2PO4 30 mg MgO 36.5 mg MgHPO4.3H2O Mangan 2.05 mg MnSO4.4H2O 2.05 mg MnSO4.4H2O 2.05 mg MnSo.4H2O Copper 0.39 mg CuSO4.5H2O 3.9 mg CuSO4.5H2O 3.9 mg CuSO4.5H2O Zinc 2.3 mg ZnSO4.7H2O 2.3 mg ZnSO4.7H2O 2.3 mg ZnSO4.7H2O Molybdenum 0.25 mg Na2MoC)4.2H2O 0.25 mg Na2MoC)4.2H2O 0.25 mg Na2MoC)4.2H2O Phosphorus 45 mg sub forma PO4 79 mg sub forma PO4 83.9 mg sub forma PO4 1 effervescent tablet contains 891 mg carbohydrates, corresponding to 3,6 kilo calories; moreover 300 mg Na (corr. abt. 0.7g NaCl); 1 tablet 350 mg, corr. 1.4 kilo calories. Consequently patients observing low-salt regimen should be administered capsules or tablets instead of effervescent tablets. "this combination is hereunder denominated as "Combination III". (some gold-preparation), person A, then still a resolute The method in conformity with the invention for the person, decided to reject such painful therapy, -it is long-term treatment and/or prophylaxis of rheumatic 55 unknown after how long a time and after how many diseases is characterized by the administration to the shots-and resolved to discontinue treatment of the patient of a single vitamin or a combination of various polyarthritis altogether, preferring to live henceforth in vitamins in variable quantities. pain from her "rheumatism' or to die of same. For The method of application in conformity with the person A such a resolution was a major one, for she had invention consists in the oral and/or per iniectio admin 60 always expressed a significant determination for a long istration of the preferred above mentioned active sub life of not less than 100 years. Stances. Her polyarthritis developed only slowly, but progres The new application in conformity with the invention sively, as stated above, a fact easily to be noted because as well as the method in conformity with the invention person A was checked in regular intervals (once a are applied in both, human and veterinary medicines; 65 week). for example in human beings and warm blooded ani Since about 1976 the patient had attacks of debility, mals, such as horses, cattle, cows, dogs, cats asf. which at the beginning were simply attributed to old Hereunder, two cases are described: age and considered to be independent of polyarthritis. 4,619,829 11 12 Only when she started to complain more specifically still in November 1982 showed clear signs of traces of about stiff fingers in the mornings too, polyarthritis was alterations, which however are also subsiding. taken into consideration. "Morning stiffness in the fin The hands of the patient A, years ago and for years gers' prevented her from getting dressed immediately highly sensitive due to pain- and pressure-sensitivity, after wake-up, to wash and prepare her breakfast. Per are typical geriatric hands, completely free however of son. A lives by herself in a one-room apartment, -look polyarthritic symptoms: One can today pump them ing herself after her little household. She stated that she unhestitatingly with no pain felt by the patient. had to loosen her fingers by exercising for at least half Occasional pains in the right shoulder and the right an hour or a full hour. Moreover she distinctly tended knee (person A blames same on an imminent change of 10 weather) are supposedly only signs of attrition, as al to get tired quickly and to feel pain in the wrists, the most not inflamed any more. front phalangeal joints (except the thumbs); the skin on A remarkable fact is to be seen insofar as person A the phalanges in pain (front) swell tightly and turned has, since she seems to have overcome her polyarthritis reddish-violet and became inflamed and tense, all of thanks to "Combination III', gained weight in 1981 which was so painful that person A was not to be despite her old age, lightly though but noticeably in the touched at her hands. 15 The fingernails, those on the thumbs included, be light of an ever decreasing quantity of food-intake, -she came brittle and somehow squamous, started to loosen gained about 23 to 3 kg. themselves from their matrixes and tool unusual forms. CASEB Especially the two thumb-nails tended to ascend. Imme 20 Male person B was born May 24, 1920 in Atkarsk (on diately next to the left wrist, at the level of the upper the Volga river) in the USSR, in the midst of a famine. most thumb-phalanx, a big and very painful swelling The family of person B was expelled 1924 from the appeared, not very hard. Patient never admitted any USSR as undesired aliens (Swiss). Ever since, person B fever. She never was persuaded to actually measure her lives in Switzerland. temperature. 25 Father of person B died at the age of 59 (1948) of lung The right shoulder and the right knee pained doubt cancer. Both elder sisters of person B died at the ages of lessly so much that she started, for instance, to each 45 and 58, both of carzinoma of the breast. using her left hand, obviously to avoid to move her Polyarthritic diseases did not occur with either father right shoulder. Despite this development, going back to or sisters of person B. Mother of person B manifested years, the old lady remained stubborn: she steadfastly 30 polyarthritic symptoms at an advanced age only. First refused to take any medicaments, even "light' analge symptoms directing to polyarthritis appeared in the case SCS. of person B about 9 years ago, i.e. in 1973: a singular, In such circumstancrs the only thing left was to per semi-hard and painful swelling on the middle joint of suade her to at least take some tonic-a Geriatric Agent the right index of great obstinacy (it still exists today to for instance-to fight off more frequent attacks of debil 35 a diminished extent but free from pain, thanks to a ther ity and great fatigue. To this she agreed and the afore apy with "Combination II'). No great attention was mentioned "Combination III' was prescribed. Ever paid to this appearance. About 3 years ago, in 1979, it since about 1976/1977 person A takes daily, regularly became observable that person B started to wake up in and uninterruptedly one capsule of "Combination III'. the mornings with finger-stiffness. After several months Shortly after staring the intake of "Combination III', 40 all front phalangeal joints (with the exception of the the first positive reactions were to be noted insofar as thumbs) showed red, painful swellings, which were attacks of debility began to disappear, slowly but tightly filled and which in the beginning of 1982 became clearly. Arthritic pains however persisted, fluctuating so unpleasant and handicapping for person B that he from sharp to untolerable, depending on weather condi had to fear to lose the faculty to write by hand or to tions and other dispositions; consequently pains did not 45 type on the typewriter. The front phalanges became reduce, complaints about mobility of hands, fingers, thick swollen and in the finger-tips there was a formica right knee and right shoulder persisted immutably, only tiontingling. The hands became so sensitive and pained the general state of health of the patient, as far as one so much that person B avoided whenever possible to may speak of same in the patient's condition, seemed to shake hands with people. Person B suffered so much turn to the better, despite of the advancing old age. 50 from pains in hands and fingers, that he resolved to take Person A remained adamantly negative as regards all resolute measures: person B started to take "Combina attempts to convince her to agree to the intake of some tion III'. medicament against her "rheumatic' pains. The first 30 capsules of "Combination III' did not After many months of intake of the "Combination bring the effect hoped for, on the contrary, an addi III' (the patient must have been taking the "Combina 55 tional peculiar idiosyncrasy developed against the prod tion III' for at least 8-12 months), person A started to uct: particular parts of the face started to "bloom', make remarks about her feeling better, how knee and turned unhealthy-red, patchy, forcing to remove "Com shoulder were no more continuously in pain and that bination III' with the result that the allergy disappeared hands and fingers ached less. One could observe how promptly. "Combination I' and "Combination II' were some of the afore-described symptoms started to disap 60 taken alternating. In June 1975, person B fractured his pear, most strinkingly with the finger-nails, the front little right finger, requiring an operation. After the phalanges: the inflammation of the fingers receded "screw' had been removed, the afflicted joint was gradually. Person A stated that the morning-stiffness of slightly sensitive for some time. About 3 years later, the fingers, which disturbed her so much, prevailed for only the operated-on finger-joint first started to show a shorter. Formerly such stiffness lasted for periods up 65 signs of inflammation and hardening. This inflammation to two hours; now after one half hour only the stiffness of the finger-joint was of traumatic origin but persisted was gone. Her finger-nails began to look more or less so long until the other 7 fingers showed similar inflam "healthy'. Only the two thumb-nails, most afflicted, mation- and pain-symptoms. 4,619,829 13 14 To fight off these unpleasant appearances "Combina X-rays exist which would allow comparisons. The tion I"/"Combination II' were employed (one tablet above mentioned singular swelling on the middle joint daily; effervescent tablets were avoided for their con of the right index has receded pointedly, only after tents of calcium, because person B had had his bout considerable time, i.e. only months after intake of with kidney-stones!) and it could be observed how, after 5 "Combination I"/"Combination II”. about 8-12 months, first of all the front joint of the Besides: Person B is non-smoker since 20 years and traumatised little finger healed so well that the remain- takes nothing but "Combination I/"Combination II' ing knot on the joint was completely free from pain and occasionally only if need be a medicament against even when strong pressure was applied. headaches (Tonopan) and feels, after having overcome After another 8-10 months, the inflammation of the 10 a polyarthritis, which was in the offing, completely in joints as well as the inflammatory appearances on the 8 good health. finger-joints (front) disappeared. There only must be The life of person B went through two health-events: added that, once one stops for some time the intake of In 1949 he suffered from tuberculosis (closed), evi "Combination I'/"Combination II' (for about 10-14 denced by photofluorography, which was completely days), thereupon the joints of the 7 fingers, on which 15 cured; in 1968 person B fell victim to a serious car-acci the idiopathic inflammatory process took place, start to dent, the consequences of which were a complicated pain, not acute yet, not violently, whereas the trauma- fracture of the left arm. Those fractures were artfully tised little right finger does not react to the stoppage. repaired by osterosynthesis (2 titanium-plates with 13 Such tests of stoppage, tried several times, always screws): Person B is 1982 still wearing those two plates had to be abandoned after 10-14 days, in order not to 20 on his bones inclusive of the 13 screws without feeling run the risk to call for renewed inflammations and pains. no botheration at all. In earlier years, person B often suffered from po- As may be gathered from these two cases, the long lyarthritic the pains in his left shoulder and left ankle, term application of for instance "Combination I', pains lasting not very long and which called for no "Combination II' and "Combination III', can trans special attention. It is however noteworthy that those 25 form a manifest polyarthritis into a latent state of com sporadic occurring polyarthritic pains have completely plaintlessness and painlessness, whereas the so-called disappeared, as a side-effect so to speak, just that person "massive-doses' during the first months of therapy do B still lives with a probably ossified swelling on the not produce either positive or negative effects. Short metatarsal bone, which does not hurt any more and is term and middle-term applications of preparations be free from pain. 30 longing to this group do not call for positive results as In connection with the disappearance of polyarthritis regards polyarthritis. in the fingers of person B, another phenomenon has For these reasons it is important to especially empha been observed: on some front finger-joints distinct knots size that therapy (and prophylaxis) with the aforemen remained. Today they are completely free from pain as tioned preparations and the whole group of such prepa long as the intake of "Combination I'/"Combination 35 rations has to be on long-term over months. II' continues,-these distinct knots are receding ever so The following table shows further data with respect slowly. It is impossible to prove this phenomenon, as no to the aforementioned persons A and B:

TABLE Therapy: of the rheumatism (of the primary chronicle polyarthritis) Period of therapy: between 18 and 60 months Number Patient's Daily dosage of inv, Strength Morning Subjective Functional Sclerodermic Side sex and age sec caption joints of grip stiffness feeling Status Fatigue Pains symptoms effects Peron A, female, months 92 years of age 20 O O O O O O O Oe 3 20 O O 0 0 O 0 0 OS 6 20 1. 2 2 2 O O role 9 12 2 3 2 1. 1 Oe 12 8 3 3 3 2 2 2 1 Ole 18 2 4 4 4 3 2 3 4 Oe 24 3 4. 4. 4. 3 3 3 4. O 30 3 4. 4 4 3 2 3 4 One 36 2 4 4. 4 4 2 4 4 One 42 2 4 4 4. 4. 3 4 4 One 48 2 4. 4 4. 4. 3 4. 4 O6 54 2 4 4. 4 4. 4 4. 4 Oe 60 2 4 4 4 4 4 4. 4 Othe Person B, months male, 62 y.old 9 O 0 O O - O -- One 3 9 O O O O - O - Ole 6 6 2 2 3 3 - 2 --- none 9 2 3 3 4. 4. --- 3 m---- One 12 O 4 4. 4 c 4 - 4 - One 4,619,829 15 16 TABLE-continued Therapy: of the rheumatism (of the primary chronicle polyarthritis) Period of therapy: between 18 and 60 months Number Patient's Daily dosage of inv. Strength Morning Subjective Functional Sclerodermic Side sex and age sec caption joints of grip stiffness feeling Status Fatigue Pains symptoms effects 18 O 4 4. 4. 4. m 4. m One Caption of table The following marks have been applied in order to characterize results of therapy: 0 is no improvement 1 = slight improvement = satisfactory improvement 3 = excellent improvement 4 = free from symptoms - = no occurance of relevant symptoms 0.15 mg Biotin, and 10 ug Vitamin B12. The female person took in daily one capsule contain 8. The method of claim 1 in which the vitamin com ing "Combination III". position administered comprises The male person took in daily alternating one lac 15 mg Vitamin B1 quered tablet, containing "Combination I", or one tablet 20 15 mg Vitamin B2 containing "Combination II”. 50 mg Nicotinamide (PP-Factor) I claim: 10 mg Vitamin B6 1. A method for the treatment of polyarthritis which 25 mg Calcium pantothenate comprises the administration for a period of time of at 0.15 mg Biotin least 5 months of an anti-arthritic effective amount of a 25 10 ug Vitamin B12, and vitamin composition comprising the combination of (a) 500 mg Vitamin C. about 0.15 to 0.5 mg of biotin, (b) about 5 to 20 mg of 9. The method of claim in which the vitamin com vitamin B1, (c) about 2 to 15 mg of vitamin B2, (d) about position administered comprises 20 to 50 mg of nicotinamide, (e) about 2 to 10 mg of 25,000 I.U. Vitamin A vitamin B6, (f) about 4 to 10 ug of vitamin B12 and about 30 20 mg Vitamin B1 3 to 25 mg of pantothenic acid or the alcohol or calcium 5 mg Vitamin B2 salt thereof. 50 mg Nicotinamide 2. The method of claim 1 in which the administration 10 mg Vitamin B6 is for at least six months. 10 mg Panthenol 3. The method of claim 2 in which the administration is 0.25 mg Biotin (Vitamin H) is for at least one year. 5ug Vitamin B12 4. The method of claim 3 in which the administration 1 mg Folic Acid is at least two years. 150 mg Vitamin C 5. The method of claim 1 in which the vitamin com 1,000 I.U. position additionally contains a mineral. 40 10 mg Vitamin E, 6. The method of claim 1 in which the vitamin com 435 mg CaHPO4.3H2O position additionally contains a pharmaceutically ac 10 mg Fe reduct, ceptable carrier. 36.5 mg MgHPO4.3H2O 7. The method of claim 1 in which the vitamin com 2.05 mg MnSO4.4H2O position administered comprises 45 3.9 mg CuSO4.5H2O 15 mg Vitamin B1 2.3 mg ZnSO4.7H2O 15 mg Vitamin B2 0.25 mg Na2MoC)4.2H2O, and 50 mg Nicotinamide 83.9 mg Phosphorus sub form a PO4. 10 mg Vitamin B6 sk k sk. k. k. 25 mg Calcium pantothenate 50

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