NZ206039A - Contraceptive vaginal tablets containing boric acid and vitamin k3 - Google Patents

Description

New Zealand Paient Spedficaiion for Paient Number £06039 206039 Priority Date{s): Complete Specification Filed: Class: &$!JCZ5-J2?t Publication Date; •«• «P>5 • . • • • P.O. Journal, No: .. 127$.

DRAWINGS N.Z.No.

NEW ZEALAND Patents Act 3953 COMPLETE SPECIFICATION 2£_E£§E5EiD2_t*ieiEI}- * ^ We, DR. ANDRAS KOVACS, 1065 Budapest, Bajesy Zs. ut 19/a. Hungary; DR RUDOLF SZEBENI, 2131 GOD. Beke u 48, Hungary; and Corvin korut 52, Hungaryj a\V l,4-H'\g<*.<v>cur* do hereby declare the invention, for which we pray that a Patent may be granted to us, and the method by which it is to be performed, to be particularly described in and by the following statement : - °v The invention relates to contraceptive vaginal tablets being free from hormones as well as to a process for preparing them.

As it is known, three methods are known - except the 5 operations - for hindering the occurrence of the undesirable pregnancy. These are the condoms, the intrauterine instruments and the vaginal pessaries (mechanical instruments) which hinder the occurrence of the pregnancy by using hormonal preparations or local spermicidal preparations 10 being free from hormones.

All the known methods have, however, disadvantages which do not make possible the general application. It is known that not every conceptive age-group may use the preparations containing hormones. Certain persons, who could 15 take these preparations in view of their age, are deprived of employing them owing to the side effects. From among the mechanical instruments the condom and the vaginal pessary cause in certain cases uncomfortable feeling or require preparations destroying the illusions. The intrauterine 20 instruments are free from these disadvantages, in contradiction to that not all persons may wear as well as even the jungest age-group may not use them. A further disadvantage of these instruments is that they may be put up only by the physician. In case of the preparation being free 25 from hormones no contraindication of the age-group exists. These are rarely applied, however, per se since they are not reliable enough.

The efficiency of the known contraceptive instruments 2 06 039 and methods is characterized by the so-called Pearl-index. This is a number which shows that from among 100 conceptive women using the instrument or method in question how many will be pregnant during a year. The Pearl-index of the 5 contraceptive instruments and methods is stated in the following Table.

Table vaginal irrigation 29,3-4-0,8 coitus interrupted 12-38 Ogino-Knaus rule 12-34-,5 foam tablet 11,9-42,8 vaginal pellet 75 7-4-2,3 diaphragm 6,1-33?6 jelly 6,4-41 vaginal pessary 6,0-29 condom 6-28 intrauterine instrument 0,9-8 hormonal preparation 0-1,7 From the data of this Table it can be seen that 20 only the hormonal preparation possess the safety desired, the efficiency of the preparation containing only chemical substances fall far behind that of the hormonal preparations.

The aim of the present invention was to find a 25 vaginal tablet being free from hormones which possess the same efficiency as the hormonal preparations and do not show, the disadvantages thereof, which tablets may be used without any limitation of the age or the physical condition. 20603 The vitamin and the adduct thereof with sodium t bisulfit are widely used in the therapy e.g.- for treating icterus occlusion, pre- and postoperative treatment in cholemia, biliary fistula, ulcerative colitis, dysentery, 5 steatorrhea, sprue, celiac disease, hemophilia of the newborn, jaundice, salicylism, purpura, thormbophenia, serum sickness, urticaria, haemoptoe. The contraceptive effect of these compounds has not been described yet.

The therapeutic use of boric acid and tartaric acid 10 is also known. The boric acid is used for rinsing cavities owing to its weak disinfectant effect, the tartaric acid is applied for regulating the pH of the preparations due to its weak acidic reaction.

It was surprisingly found that a preparation, which correspond to the above requirements, may be obtained when 0,2 to 3,0 parts by weight of boric acid, ,0 to 20 parts by weight of tartaric acid, 1 to 2 parts by weight of vitamin K^-sodium bisulfit ^adduct, 0,8 to 1,2 parts be weight of polyvinyl pyrrolidone, 2 to 5 parts by weight of magnesium stearate, 8 to 12 parts by weight of carboxymethyl cellulose, 8 to 12 parts by weight of lactose and 50 to 65 parts by weight of microcrystalline cellulose are homogenized thereafter pressed to tablets.

The tablets contain preferably 5 mg of vitamin K-,- 3 -sodium bisulfit adduct pro tablets. Such a tablet has a total weight of about 500 mg.

The vaginal tablets of the invention should be 206039 wetted before using it thereafter put into the back-vaginal fornix. Here the tablets disintegrate quickly owing to the moisture and form a suspension. This suspension covers the cervix and paralyzes the spermiums being thereon. The rest 5 of the preparation may be removed by irrigation. The use of the tablets does not cause uncomfortable feeling, the tablets disintegrated in the vagina do not have any noxious side effect.

Further details of the invention are shown in the 10 following Examples without any limitation thereto.

Example 1 Homogeneous powder mixture is prepared from 2,0 g of powdered boric acid, 100,0 g of powdered tartaric acid and 100,0 g of microcrystalline cellulose. Separately 10,0 g 15 of vitamin K^-sodium bisulfit adduct, 10,0 g of polyvinyl pyrrolidone (Polyplasdon XL), 50,0 g of magnesium stearate and 100,0 g of carboxymethyl cellulose are homogenized. The two powder mixtures are mixed thereafter 648,0 g of micro-crystalline cellulose are admixed. 1000,0 g of the powder 20 mixture are obtained, from which 2000 tablets each weighing 500 mg and having a diameter of 12 mm are pressed without edges.

Some properties of the tablets so obtained are summarized as follows: abrasion hardness (ERWEKA-TAP): after 5 minutes after 10 minutes 1,46 % 3,02 % 1,29 % 2,86 % 206039 compression strength (ERWEKA): 14,3 N average height of the tablets: 4,52 mm disintegration time (flask method according to PA.Mg.Vl): 9 to 10 minutes, Example 2 Tablets are prepared according to the process described in Example 1 with the following composition: boric acid * 5,0 mg tartaric acid 50,0 mg * vitamin K^-sodium bisulfit adduct 5)0 mg * polyvinyl pyrrolidone 5»0 mg magnesium stearate 15,0 mg carboxymethyl cellulose 50,0 mg lactose 50,0-mg microcrystalline cellulose 520,0 mg 500,0 mg Example 3 Tablets are prepared according to the process 20 described in Example 1 with the following composition: boric acid 15,0 mg tartaric acid 50,0 mg vitamin K^-sodium bisulfit adduct 5,0 mg polyvinyl pyrrolidone 5,0 mg magnesium stearate 15,0 mg carboxymethyl cellulose 50,0 mg lactose 50,0 mg microcrystalline cellulose 310,0 mg 500,0 mg 206039 Example 4- Tablets are prepared according to the process described in Example 1 with the following composition: boric acid 1,0 mg tartaric acid 100,0 mg vitamin K^-sodium bisulfit adduct ,0 mg polyvinyl pyrrolidone ,0 mg magnesium stearate ,0 mg carboxymethyl cellulose 50,0 mg . lactose 50,0 mg microcrystalline cellulose 27^-,0 mg 500,0 mg Example 5 Tablets are prepared with the following composition: boric acid 1, 0 mg tartaric acid VJI o ** 0 mg vitamin K^-sodium bisulfit adduct , 0 mg polyvinyl pyrrolidone , 0 mg magnesium stearate , 0 mg carboxymethyl cellulose 50, 0 mg lactose °, 0 mg microcrystalline cellulose 319, 0 mg 500, 0 mg Example 6 Tablets are prepared with the following composition: boric acid 5,0 mg I 206 03 tartaric acid 50>0 mg vitamin K^-sodium bisulfit adduct 10,0 mg polyvinyl pyrrolidone 5,0 mg magnesium stearate 15,0 mg carboxymethyl cellulose 50,0 mg lactose 50,0 mg microcrystalline cellulose 315,0 mg 500,0 mg Example 7 Tablets are prepared with the following composition: boric acid 15,0 mg tartaric acid 50,0 mg vitamin K^-sodium bisulfit adduct 10,0 mg polyvinyl pyrrolidone 5,0 mg magnesium stearate 15,0 mg carboxymethyl cellulose 50,0 mg lactose 50,0 mg microcrystalline cellulose 305,0 mg 500,0 mg Example 8 Tablets are prepared with the following composition: boric acid 1,0 mg tartaric acid 100,0 mg vitamin K^-sodium bisulfit adduct 10,0 mg polyvinyl pyrrolidone 5,0 mg magnesium stearate 15,0 mg 20603 9 lactose 50,0 mg carboxymethyl cellulose 50,0 mg microcrystalline cellulose 269,0 mg 500,0 mg The following in vitro and in vivo tests were performed with the tablets of the invention.

In vitro test Sperms having been obtained from 32 normo zoospermia 10 persons were examined. From the sperm 1 ml quantities containing 10 to 100 millions of spermiums were mixed with 1 ml suspension obtained from 1 tablet at +38 °C on a watch--glass. The motion of the spermiums was observed. The partial immobilisation began 1 minute after the mixing and became 15 complete in 5 to 10 minutes depending on the vitality of the spermium. The immobilized spermiums became eosin binder which means the cell death. This process is irreversible. The spermiums could not be revived either by changing the pH or by adding fresh serum or by other methods.

In vivo model test The following test was carried out at women being in ovulation period. The tablets prepared according to the invention were wetted by water thereafter put into the back-vaginal fornix. After 5 minutes the vagina was exposed 25 and each 2 ml of a sperm having a concentration of 160 to 240 millions spermium/ml were injected onto the women's cervix. The exposing instrument was removed and after 5 and 10 minutes repeated exposures were performed thereafter the 20603 content of the vagina was examined.

According to the microscopic examinations the immobilization is 50 % after 5 minutes, while 100 % after 10 minutes.

In vivo application test f The tablets were applied at women who were proved to be conceptive and till the time of the examination protected themselves only by the Ogino-Knaus rule. Among these women pregnancy occured only in two cases during a one year period. 10 In view of this fact the tablets of the inventions have the same efficiency as the intrauterine instruments (the Pearl--index was 2).

The women examined were controlled by gynecologic examination in every two or three months so that the 15 occasional side effect on the vagina or the damaging effect on the mucous membrane should be determined. Such cases were not found. In view of the above described it can be stated that the vaginal tablets of the invention are suitable for the modern contraception in every respect. 206039

Claims (4)

WHAT WE CLAIM IS i

1. Contraceptive vaginal tablets characterized in that they contain 0.2 to 3 parts by weight of boric acid, 5 10 to 20 parts by weight of tartaric acid, 1 to 2 parts by weight of vitamin K^-sodium bisulfite adduct, 0,8 to 1.2 parts by weight of polyvinyl pyrrolidone, 2 to 5 parts by weight of magnesium stearate, 8 to 12 parts by weight of carboxymethyl cellulose, 10 8 to 12 parts by weight of lactose and 50 to 65 parts by weight of microcrystalline cellulose.

2. Process for preparing contraceptive vaginal tablets characterized in that 0.2 to 3 parts by weight of boric acid, 15 10 to 20 parts by weight of tartaric acid, 1 to 2 parts by weight of vitamin K^-sodium bisulfite adduct, 0.8 to 1.2 parts by weight of polyvinyl pyrrolidone, 2 to 5 parts by weight of magnesium stearate, 8 to 12 parts by weight of carboxymethyl cellulose, 20 8 to 12 parts by weight of lactose and 50 to 65 parts by weight of microcrystalline cellulose • and are homogenized(thereafter pressed into tablet form.

3. A tablet according to claim 1 substantially as herein described or exemplified.

4. A process according to claim 2 substantially as herein described ory^exemplified, X DR. ANDRAS KOVACS, DR.RUDOLF SZEBENI and BELA KOSZEGI. By Their Attorneys HENRY HUGHES LIMITED