RU2077325C1 - Method of treatment of the acquired syphilis forms - Google Patents

Abstract

FIELD: medicine, venerology. SUBSTANCE: method involves penicillin-therapy followed by intramuscular administration of durant penicillin preparation. Penicillin-therapy is carried out by intravenous drop administration of preparation, twice per 24 h, total daily dose is 20 000 000 U, not less. EFFECT: simplified method of treatment. 4 cl

Description

 The invention relates to medicine, in particular, to methods for treating sexually transmitted diseases, namely, various forms of early acquired syphilis.

 To assess the novelty and inventive step of the claimed solution, we consider a number of well-known technical means of a similar purpose.

 In practice, the work of hospitals with a dermatovenerological profile is currently using the officially recommended method for treating patients with primary seronegative, primary seropositive and secondary fresh syphilis, which consists in the treatment of water-soluble penicillin administered intramuscularly at short intervals (3 hours) for a long period (14 -16 days).

 Some variants of this technique include a combination of water-soluble penicillin and its durant preparations (bicillin-1, bicillin-3, bicillin-5), administered sequentially until a total dose of 36.0-51.2 million units is reached using these methods.

 To treat secondary recurrent and latent early syphilis, water-soluble penicillin is administered intramuscularly at 0.4-1.0 million units every 3-4 or 6 hours for 28 days.

 To increase the intervals between injections, additional use is necessary. A combination of sequential administration of water-soluble soluble penicillin with its durant drugs is used to treat these forms of syphilis, but in order to increase the effectiveness of therapy, it is also recommended to prescribe additional treatment with bismuth drugs in 2 courses.

 Significant disadvantages of this technique in all its known variants is the following.

 1. The methods do not provide the necessary treponemocidal concentration of penicillin in the cerebrospinal fluid (cerebrospinal fluid) in all cases of their use, which does not allow to organize an attack on the pathogen and to ensure complete rehabilitation of the patient's body.

 This reduces the therapeutic effectiveness of the treatment and creates the possibility of developing late forms of syphilis, damage to the nervous system.

 2. The methods require a long stay of the patient in a hospital with a special profile, which increases the cost of paying sick leaves, taking the patient out of the sphere of material production for a long time. These circumstances significantly reduce the economic cost-effectiveness of treatment.

 The first of these shortcomings also affects the well-known syphilis treatment methods adopted by the United States Centers for Disease Control in 1982, consisting in the intramuscular administration of durant penicillin preparations in doses of 2.4 million units.

 Given the above-mentioned shortcomings of all existing methods of treating syphilis, the task of increasing the therapeutic efficacy and economic cost-effectiveness of treatment is very relevant, especially at the present time, when there is a significant increase in the number of sexually transmitted diseases, including syphilis.

 An attempt to solve this problem was carried out in the treatment of early forms of syphilis, based on the endolymphatic administration of penicillin sodium salt and intramuscular injection of one of the durant preparations of penicillin, namely, bicillin-5, at a dose of 4.5 million units, see "Guidelines of the Ministry of Health RF "Endolymphatic penicillin therapy of syphilis", Moscow, 1992, p.5.

 According to this method, the sodium salt of benzinpenicillin at a dose of 1.0 million units is administered endolymphatically every 4 hours for 1-2 days, after which a single intramuscular injection of bicillin-5 at a dose of 4.5 million N.

 The maximum total dose of an antibiotic in the treatment of secondary recurrent syphilis is 46.5 million units.

 To ensure the possibility of administering drugs, peripheral lymphatic vessels are catheterized first, after which the drugs are administered manually, or using automatic syringes, lymph injectors, dispensers, etc. Treatment is carried out in a dermatovenereological hospital and involves a limitation in the regimen for patients for a certain time.

 By the greatest number of similar features and achieved by using the result, this technical solution is selected as a prototype of the claimed invention.

 The known technique allows to increase the therapeutic efficacy of treatment of all forms of early acquired syphilis, which is confirmed by the rapid disappearance of pale treponema from the surface of syphilis (2.5 hours), as well as by the regression of syphilis by negation of the complex of serological reactions in a relatively short time (from 37 days in the treatment of primary seropositive syphilis up to 120 days in the treatment of secondary recurrent syphilis). The technique allows to reduce the time of inpatient treatment.

However, this prototype technique has a number of significant drawbacks that do not allow us to achieve our goal, namely:
1. The implementation of this technique requires the implementation of a number of technical complex operations (categorization of peripheral lymphatic vessels, infusion of drugs into the lymphatic vessel, etc.), which requires special skills and conditions, a set of operating equipment, and highly qualified personnel.

 To achieve a triponemocidal concentration, frequent repeated administration of penicillin is used, requiring restrictions in the regimen for the patient and constant medical supervision.

 3. This method of treatment poses a certain danger to medical personnel, because increases the likelihood of contracting syphilis.

 The objective of the invention is to significantly simplify the treatment method while ensuring its high therapeutic effectiveness.

 The essence of the claimed invention is expressed in the following set of essential features, sufficient to achieve the above technical result.

 According to the invention, in a method of treating early acquired forms of syphilis, consisting of penicillin therapy, for example, with a water-soluble salt of benzylpenicillin, followed by intramuscular administration of one of the durant preparations of penicillin at a dose of at least 4.5 million units, penicillin therapy is carried out by intravenous drip of the drug twice a day with a total daily dose of at least 20.0 million units

 This is the totality of essential features that provides a technical result in all cases to which the requested amount of legal protection applies.

In addition, the claimed solution has optional features characterizing its particular cases, specific forms of its material embodiment or special conditions for its use, namely:
intravenous penicillin therapy can be carried out for 3 days, while one of the durant preparations of penicillin is administered once;
intravenous penicillin therapy can be carried out for 3 days, while one of the durant preparations of penicillin is administered twice with an interval of 7 days;
intravenous penicillin therapy can be carried out for 10 days, and one of the durant preparations of penicillin is administered twice with an interval of 7 days.

 The claimed technical solution is new, as it is characterized by the presence of a new set of features that is absent in all known objects of equipment of a similar purpose.

 The immediate technical result, which can be obtained by implementing the claimed combination of features, is that over a certain period a stable excess of the minimum tryponepocidal concentration of penicillin in cerebrospinal fluid and blood serum is ensured.

 This technical result is not a consequence of the well-known properties that are manifested separately by signs that are well-known from other objects of technology, such as, for example, intravenous administration of drugs, but is a property of only the totality of signs stated in the first paragraph of the formula, including such completely new signs like intravenous drip of large doses of penicillin followed by intramuscular injection of one of its durant drugs.

The receipt of the mentioned technical result ensures that the object of the invention as a whole has a number of new useful properties, namely:
guaranteed reorganization of the body;
reduction in the time of negative serological reactions;
simplification of the implementation of the method.

 This allows you to recognize the claimed technical solution meets the criterion of "inventive step".

 The claimed method is as follows.

The treatment consists of a combined sequential administration of the benzylpenicillin sodium salt intravenously and the durant drug penicillin (bicillin-3 or bicillin-5) intramuscularly:
a) Option I
Patients with early acquisition of syphilis (primary seronegative syphilis, primary seropositive syphilis, fresh secondary syphilis, secondary recurrent syphilis, early latent syphilis) with a disease duration of up to 6 months benzylpenicillin sodium salt is administered intravenously dropwise twice a day (20 days) 3 days (total dose of 60 million units), then 4.8 million units of bicillin-3 or 4.5 million units of bicillin-5 are intramuscularly administered once;
Sick secondary
b) Option II
For patients with secondary recurrent and latent early syphilis with a disease duration of more than 6 months, benzylpenicillin sodium salt is administered intravenously drip twice a day (daily dose of 20 million units) for 3 days * total dose of 60 million units), then 4.8 million twice .Unit of bicillin-3 and 4.5 million units of bicillin-5 intramuscularly with an interval of 7 days;
c) Option III
Patients with various forms of early acquired syphilis with manifest manifestations of damage to the nervous system or internal organs, serological resistance, benzylpenicillin sodium salt are injected intravenously twice a day (daily dose of 20 million units) for 10 days (total dose of 200 million units), then 4.8 million units of bicillin-3 or 4.5 million units are introduced twice. bicillin-5 intramuscularly with an interval of 7 days.

 The application of the proposed method allows preserving the concentration of penicillin necessary for effective treatment in blood serum in the range of 0.06-10.46 U / mm and in cerebrospinal fluid in the range of 0.13-1.13 U / mm for various periods after iv water-soluble administration penicillin, which is several times higher than the minimum treponemocidal concentration of the drug, and ensures stable long-term preservation of the therapeutic treponemocidal concentration of the drug in the body for a total of 23-30 days after intramuscular injection penicillin preparations.

 As evidence of the feasibility of the claimed technical solution, we consider a number of specific cases of its use in medical practice.

 Patient M. 24 years. I.B. 12762/92.

 Upon admission to the hospital on the skin of the lower abdomen in the pubic area ulcer chancre with a diameter of up to 2 cm, pale treponema was found in the discharge. Right inguinal adenitis. Serological examination prior to treatment with DAC 4+ with both antigens in titer 1/10, R. Cana and microreaction 4+, RIF ABS 4+. By confrontation, a disease duration of 1.5 months was established at the time of hospitalization. Diagnosis: syphilis primary seropositive.

 I received treatment according to option 1. Chancre resolved by 4-5 days of treatment, adenitis by 8-9 days of therapy. 1 month after treatment with SSS, R. Kana p. 2+ microreaction. After 2.3.6 months, after treatment with DAC, R. Kana, microreaction neg. RIF ABS 2+.

 Patient N. 35 years. I.B. 11332/92.

 Upon admission to the clinic on the skin of the body, an abundant, small, non-sagging, pale, pink, tear rash. On the skin of the abdomen a small amount of lenticular papules. Erythematous tonsillitis. In the area of the posterior commissure, an erosive solid chunk with a diameter of up to 1.5 cm with a serous compartment in which a pale treponema is found. Multiple papules along the crest of the labia minora and labia majora. Polyadenitis with a predominance of inguinal. Serological examination prior to treatment with DAC with cardiolipin antigen 4+, with treponemal antigen 2+, p. Cana and microreaction 3+, RIF ABS 4+.

 By confrontation, the duration of the disease is 2.5 months. by the time of hospitalization. The diagnosis of syphilis secondary fresh. I received treatment according to option I. Rosesla resolved on the 2nd day of therapy, the chancre was epithelized by the 4th day of treatment, erythematous tonsillitis by the 3rd day of treatment and papular rashes on the 4th-5th day of treatment. By the 8th day of treatment of DAC, R. Kana p. 2+ microreaction.

With serological monitoring at 2, 3, 4, 6 months after treatment of DAC, p. Cana and microreaction p. At 3 months, RIF ABS 4+, RIBT 13%
Patient F. 23 years old, I.B. N, 11251/92.

 Upon admission to a hospital on the skin of the trunk, a large ring-shaped grouping roseola on the lateral surfaces of the abdomen and chest. On the skin of the palms and soles there are single resolving papular elements with peeling according to the Bietta collar. On the left tonsil are papular elements of the type of opal plaque. Moderate polyadenitis. Pale treponema was found in discharge from papules on the oral mucosa. Serological examination prior to treatment: DAC with cardiolipin antigen 4+ in titer 1/20, with ultra-sonic antigen 4+ in titer 1/5, Kan reaction 4+, microreaction 4+, RIF ABS 4+, RIBT 98% By confrontation duration 5.5 months of illness at the time of hospitalization. Diagnosed with secondary recurrent syphilis. I received treatment according to option I. Roseola was resolved on day 2 of therapy, mucous papules on day 3, treatment, palms and soles on days 4-5.

 By day 8 of therapy, the titer of DAC with cardiolipin antigen 1 / 1-.

 After 2 months after treatment with DAC 2+, the Kahn reaction and the microreaction are denied.

 After 3 months, the USR, the Kana River and the microreaction neg.

After 4 months, DAC, R. Kana, microreaction neg. RIF ABS 4+, RIBT 9%
Patient A. 30 years old, I.B. 13106/92.

 Upon admission to the hospital on the skin and mucous manifestations of syphilis was not detected. Serological examination prior to the start of treatment with DAC with both 4+ antigens in titer 1/20, Kana river and microreaction 4+, RIF PBS 4+, RIBT 78% By means of confrontation, the duration of the disease at the time of hospitalization was 5.5 months. Diagnosis: early latent syphilis. I received treatment according to option I.

 After 1 month after treatment of DAC with cardiolipin antigen and R. Kana neg. DAC with an ultra-sonic antigen and 3+ microreaction.

 After 2 months DAC, r.Kana neg. microreaction 2+.

After 3, 4, 5, 6 months. DAC, R. Kana, microreaction neg. RIFABS 4+, RIBT 65% after 6 months. RIF ABS 4+, RIBT 35%
Patient A. 21 years old. I.B. 17308/92.

 Upon admission to the clinic, opal plaques on the tonsils and posterior pharyngeal wall, small papules on the genitals, wide condylomas in the perianal fold. Polyadenitis. Pale treponema is found in the discharge with genital warts. Upon serological examination prior to treatment with DAC with both 4+ antigens in titer 1/10, p. Cana and microreaction 4+, RIF ABS 4+, RIBT 100% By confrontation, the infection period is more than 7 months by the time of hospitalization. Diagnosis: syphilis secondary recurrent. Treatment option II. Papular rashes were resolved on the 4th-7th day of therapy.

 After 1 month after treatment of DAC, R. Kana, microreaction 3+.

 After 2 months after treatment of DAC, R. Kana neg. microreaction 2+.

After 3 months after treatment of DAC, R. Kana, microreaction neg. RIF ABS 4+, RIBT 41%
After 6 months DAC, R. Kana, microreaction neg. RIFABS 4+, RIBT 32%

Claims (1)

1 1. A method of treating early acquired forms of syphilis, which consists in penicillin therapy, for example, with a water-soluble salt of benzylpenicillin followed by intramuscular injection of one of the durant penicillin preparations with a dose of at least 4.5 million units. characterized in that penicillin therapy is carried out by intravenous drip of the drug twice a day with a total daily dose of at least 20 million ED.2 2. The method according to claim 1, characterized in that intravenous penicillin therapy is carried out for 3 days, while one of penicillin durant drugs are administered once.2 3. The method according to claim 1, characterized in that intravenous penicillin therapy is carried out for 3 days, and one of the penicillin durant drugs is administered twice with an interval of 7 days.2 4. The method according to claim 1, distinguishing I in that the intravenous penicillin carried out for 10 days, and one of repository penicillin preparations administered twice at an interval of 7 days.