JPS5962525A - Antiseptic and antiinflammatory local medicine - Google Patents

Abstract

(57) [Summary] This bulletin contains application data before electronic filing, so abstract data is not recorded.

Description

DETAILED DESCRIPTION OF THE INVENTION TECHNICAL FIELD The present invention provides a powerful double-target drug suitable for the treatment of localized skin irritation, both primary and secondary infections associated with dermatitis. Inexpensive and short-term topical antiseptic preparations with anti-inflammatory action and methods for making these preparationsPrior art Antibiotics (e.g. chloramphenicol, oxytetracycline, neomycin, gentamicin, etc.) and preservatives (e.g. glioquinoram: 5-chloro-8- Hydroxy-7-iodo-quinoline, hexachlorophene:
2.2'-dihydroxy-3,3', 5.5', 6.
Soft-1f formulations containing 6'-hexachloro-diphenylmethane, etc. as all active ingredients are widely used in the treatment of various skin infections. However, these preparations only attempt to affect the infection-causing bacteria themselves; they only affect adjuvant inflammation.
(mation) cannot be directly influenced.

To treat inflammatory dermatitis, especially in chronic cases, anti-inflammatory drugs containing corticosteroids are often used in addition to antibacterial treatment.

Formulated softgel containing both antibacterial agents and corticosteroids
F agents, such as Chlorocyto-H (8) (■...Registered commercial company. Chemical name of active ingredient in parentheses) (Anti-A ingredient: chloramphenicol, corticosteroid ingredient: Human O: l
- Chian), Tetran-Hydrocortisone ■ (Anti-1A
Ingredients: nioxytetracycline, corticosteroid ingredient: hydrocortisone), prednisolone-J■ (antibacterial ingredient: 5-chloro-8-hi)
- Toquinoline, corticosteroid component: prednisolone), or both anti-inflammatory drugs and corticosteroids.
(Antifungal ingredient: pimaricin, corticosteroid ingredient:
Hydrocortisine)・Mycozolone■ (Antifungal ingredient: 1
-[2,4-dichloro-β-(2,4-dichloro-benzyloxirahphenethyl]-imidazole, corticosteroid component: 21-thioxy-21-(4-methyl-piperazino-9-gredonisolone salt), etc. Their use in the treatment of inflammation and other skin diseases, such as eczema, can be considered a significant advance in that these dual-target combinations do not solve the problems that arise when only the whole component is applied. .

These problems can be summarized as follows: The antibacterial range 17J,+ of the antibiotics used in these pharmaceutical formulations is rather narrow. Tetran-Hydrocortiscin ■The oxytetracycline component of the soft drug is pseudomonas (pscudo
monas), Proteus and Klebsiella.
Gram-negative l1 or Staphylococcus aureus 1. f(5taphy
locoecus au-reus) or 51 grams 1 of Treptococci)
On the other hand, the chloramphenicol component of Roroside H Soft-*at has almost no effect on initial puberty.
It does not show sufficient susceptibility to Gram-negative strains such as Staphylococcus aureus and Durham-positive strains such as Staphylococcus aureus and Streptococcus strains.

Furthermore, when used in all antibiotic-containing cortical diseases, antibiotic resistance quickly develops. As a result, this procedure has the expected therapeutic f! :Not only does it not cause any damage, it may even promote the growth of pathogenic microorganisms that are resistant to them.
Chemotherapy), Churchill Livingst: y (Churchill Livingst)
one) rilffi, ayton, 1981, p.
ao6)).

In addition, these medical products have rather weak anti-
It is also worth noting that circumscribing them may cause an increase in the number of skin RFL pathogenic Jλ swarms9 [Guidelines for the Prescription]
Of Farman Iti Rikile Prevareshi 97s (G
guidelines for the prescrip
tion of Phar-maceutical
Preparations), Medicina Press, Budapest, 1
980, p. 479). For this reason, skin allergies are often observed in patients who use all of the above preparations.

Although aminoglycoside antibiotics (e.g., neomycin, gentamicin) have a relatively broad antibacterial spectrum, they are significantly more toxic than those mentioned above, and have effects on 7flTh and hearing, which may be associated with topical B [administration in large doses]. It may appear later.

Among all the preservatives applied in dermatology, formulations with a broad antibacterial spectrum'y[-5-chloro-8-
Hydroxy-7-iodo-quinoline (cryoquinolam)
The use of this compound is limited because it contains iodine, which causes skin irritation and allergies. For this reason, patients with iodine sensitivity cannot use it at all [Martindale:
Extra pha
rmacopoeia), The pharmaceutical
al Press), London, 1977, pp.
27, 72, and 823: JAMA 201
, 1009 (1967); JAMA 202
, 710 (1967): Arch.

Derm, 106-. 335 (1972)] o Furthermore,
It's a dirty piece of cloth or linen.

The side effects of preservatives should not be ignored, as many of them are rather toxic and can be absorbed through the skin. Recently, it has been found that hexachlorophene has a serious effect on the nervous system [JAMA240, 513 (19
78); J, Cl1n, Pathol.

34, 25 (1981); Lancet l
Another drawback of antibiotics and other antibacterial agents, such as hexachlorophene, iodine, and mercury compounds, is that they can cause dermatitis as a side effect due to their allergenic effects. This danger is eczema,
II against the allergic effect of ω people! This will enhance the stronger sensitivity of II N [polysensitization
ENSIBILIZATION)].

Soft If shavers containing antibacterial agents generally have a weak antibacterial effect, either alone or in combination (Pimanocoat (2), Mycozolone (2), etc.). Therefore, their antibacterial ◆l
! The scope is narrow and a preliminary test to confirm the presence of a fungal infection is successful only when applied to the sound shun.

The anti-inflammatory components of C are mostly corticosteroids.When applied to skin diseases, they exhibit excellent therapeutic effects; however, at the same time Thin 1, Makoto and skin against viruses j1
The total resistance of i is reduced. As a result, when applied to inflamed skin surfaces, it causes a secondary infection, which is manifested by an abscess-filled stage. Furthermore, by containing corticosteroids in total,
Synthetic steroids may cause systemic side effects.

Since the above-mentioned compound for treating skin diseases can only be used by those who have identified all pathogenic microorganisms in advance, Mari Nibota is considered to be ideal in practice. It's two years old. Treatment of PJ skin disease is basically carried out on regular patients, and culture is rarely performed. Therefore, the R1 outcome of treatment cannot be predicted. All the listed preparations are effective in cases of local hypersensitivity: pruritus, urticaria, skin irritation, A'A rash, and maculopapular rash (mac).
ulopapulous rash) f actual vine (chlorocyto-H■) (Guidelines for Drug Prescription, Medicina Press, Budapest, 1980, p, 128).

OBJECTS OF THE INVENTION The present invention provides that the above-mentioned combination preparations do not suffer from the drawbacks of the above-mentioned combination preparations, are stable, and can improve the patient's health. It can be applied even if it cannot be measured.

It is intended to provide a complete range of antiseptic and anti-inflammatory topical pharmaceutical products.

Structure of the invention and young fruit 9α-fluoro-11β, 21-dihydroxy-16α
, 17α-ingropylidene dioxypregna-1,
4-diene-3,20-dione (triamcinolone-acetonide) 0.025 to 0.25 LR% and 1,6-bis-(5-(4-chlorophenyl)-biguanidocouhexane dihydrochloride straddle digluconate , IL each Chlorhexidine dihydrochloride Statake digluconate) 0..25 fr, Ishi2
．． 5. The anti-IK and anti-inflammatory effects of the uninvented topical formulation, which contains all of
l and these are primary and secondary dermatitis with adjuvantitis & 1, e.g. eczem
a num-mulare), periaxial eczema (m1cr
obiale), lower limb filiform Qiji (myc
oticum cruris), pus3110 eruption (1
mPe"g'-nosum), sweat-foaming eczema (dysh
It has been traditionally applied in the treatment of S. idrosis), H. idrosis, H. idrosis, and co-infections such as contact skin moxibustion9.

Therefore, the invention relates to a pharmaceutical formulation with antiseptic and enhanced anti-inflammatory properties. The manufacturing method of these preparations is 9α-fluoro-11β, 21
-dihydroxy-16α.

17α-Ingropylidene dioxypregna-1,4
~diene-3,20-dione and 1,6~bis[5-
(4-chlorophenyl]-bicuanide]-hegisandihydrochloride and digluconate at a ratio of 1:1
by methods commonly used in pharmaceutical manufacturing, using excipients and additives commonly used in ax formulations, mixed in a ratio of 1:50 to 1:50; - 9α-fluoro-11β, 21-dihydroxy-1 as an active ingredient
6α, 17α-Ingropylidene dioxypregnath
1,4-diene-3,20-dione-3°20-dione 0.05 Z-0.25 weight 11% and l.

6-bis[5-(4-chlorophenyl)-biyanide]
-Hexane dihydrochloride or digluconate 0.2572 to 2.5 months 1% gold@soft 14 M
'), syrup, Ipn, 6e, or other sticky forms of pharmaceutical preparations.

The instantaneous ingredients contained in the formulation according to the invention are known compounds, chlorhexidine dihydrochloride or digluconate is prepared by the method disclosed in Hungarian Patent No. 175.371, and triamcinolone acetonide is manufactured by the method disclosed in Hungarian Patent No. 175.371. Jt'F No. 163,145 and -C.

By combining the respective chlorhexidine salts and triamcinolone-acetonide in all the above-mentioned conditions, it is possible to create a current topical drug composition that is more effective, safer and easier to use than previous pharmaceutical formulations. This composition has a wide range of anti-dandruff properties and will not cause any resistance during treatment.

Regarding the side effects vC that occur with commercially available preparations that have similar ridges, those who use the preparation of the present invention become weaker.

1. According to a raised bed test report, the inventive combination of triamcinolone-acetonide with its respective chlorhexidine salt unexpectedly did not respond favorably to conventional treatment with electricity. This formulation provides good treatment for skin dandruff in patients who have had severe or unsatisfactory responses. By reducing the number of bacteria on the skin surface and exerting a secondary anti-inflammatory effect, chlorhexidine completely suppresses the development of chronic dermatitis and superinfection. This ensures a more favorable situation for triamcinolone to exert its anti-inflammatory effect on the eczematous skin surface.

The efficacy of the composition of the present invention is clearly demonstrated by the softening Mll, which contains 0.1% of triamcinolone heptatonide and 1% of chlorhexidine dihydrochloride, and is enhanced by Examples 11 to 3. be done.

1.Clinical test 1.1 Open preliminary test Number of patients = 17 Diagnosis: Eczema dyslidro
si-forme) 11 cases of pemphigus vulgaris
) Six patients did not respond favorably to conventional treatment with this I.

Comment 111i: There are no cases where the reaction is immediate and obvious, and the patient progresses to an asymptomatic state. There were no side effects.

1.2 Two sets of i-test clinical trial 1@ The reference material used as a control contains 0.1@m% of triamsifuron-acetate. Both k ft'
M'l, -j-i, formulation M11 containing chlorohexidine dihydrochloride and triamcinolone-acetonide, and formulations containing only triamcinolone-acetonide, all moistened with the same soft-+V base. ,code·
Served with No. 118. Both the patient and the doctor 111f do not know which manufacturer's RFL) was used. Code t will only be known to the test taker. The preparation was used to treat counterinfections that were symmetrical to itself. Which side is treated with each formulation is randomized.

, one person's polymorphism: 30 Diagnosis: Eczema nummulare (eczema nummulare)
) 19 cases of filamentous fungal eczema (eczema mycot)
icum) 3 cases IS yhal, b eczema (ec
ze+na impetiginosum) 3 symptoms series dyshidros is
The test data obtained from 5 cases were evaluated in a divided manner. The results achieved with combination products are the same as those achieved with City J& products! 7 Significantly better (p=0.05
).

No side effects were observed.

Evaluation: Both the open test and the double i test show that the ointment containing chlorhexidine dihydrochloride + triamcinolone-acetonide gold cannot be completely cured by conventional treatment. It was confirmed that it shows excellent therapeutic effects even in obvious dermatitis.

No side effects or allergic reactions were observed in any case.

According to research, the combination drug has M effect on the following cases: Is mkan 1/hi due to the 9 factors of straightness being primary or secondary? All types of eczema, including numerular eczema, bacterial eczema, fungal eczema, and claris-like eczema on the lower legs.
impetiginosum), sweat foam eczema, 1
11. Stop eruption Chuyuchin, Jinjochutenchofui. The inventive combination is more advanced than conventional formulations with similar compositions, such as prednisolone J, tetrahydrococcicin, riOOcytof, mycozolone, etc. It is effective.

2. Open clinical trial A total of 71 people conducted a skin pathology clinical trial on the uninvented compounded soft drink.

Patient description V]: Eczema bacteriale
18 filamentous unisex jf3 (eczema
mycoticum) 13 Contact eczema (ec
zema contactum)6 endogenous eczema (ecz
ema endogenes) 1 exzema ronicosur
n) 2jy ;/' :, > balanoposthjtis canbida
) 3ijl Lower limb painless rJt id (ulcus cruris
) 3gypi acne
pustulosa) 7 deishydrosysma = (dyshydrosls manj
) 7 dyshydrosis pedis (dys
hydrosis pedis) 8 rare skin,
11 dermatitis intertrig
Microscopic examination of 20 of the 171 patients was performed on culture specimens, and the following pathogens were detected: Staphylococcus aureus P (5 taphylococcus
aureus), Klebsiel box (Klebsiel)
la), green rW & III (Pseudomona
s aerugi-nosa), strange transformation evil (Pro
teus m1rabilis), large intestine trouble (Esch
Ericbia colt), Candida Atsuguchi (ca.
ndidaalbicans), epidermophyte (Epi
dermophyta fungi).

Patients were previously treated with known formulations. 53 out of 71 people (
74.6%) of patients did not recover.

Before applying Fuenmei Ointment 薊, treat with regular preparations and summarize the results in the first article.

The following margin is Mito, 4uJ formulae (Formulae Norm)
ales) [Fo, -N), .

■ Bancarica Medicina Press (v.

Hungarica Medicina Press
), Pudavest, 1967] Fuenisteil [dimet
hindenum maleinicum) ] Futrocort [triamcinolone-acetonide (triam
cinolon-acetonid)) fungifen [pentachlorophenol
ophenol) ] mycozolone [maz ipredron hydrochloride
i cum ) + miconazole (micona-zo
lum)) ・Pimafucin
)) Trypsin [trypsin (trypsinum)
) Toshio is procain hydroc
hloricurn)) lolinden [pival is flumethacin (flumetha-zolum piva)
licum) ] Laurindetin [flumethacin pipalate + salicylic acid] Canesten [rioo trimazole (cblorotri
mazol) ] Flucinal N [fluocinolone acetonide + neomycin] When the same thinking as above (71 patients) was treated with the combination soft Ftf agent of the present invention, it was found that the majority of patients (95%) were successfully treated. Ta.

The degree of evaluation of the treatment using the compounded emollient of the present invention by evaluating all the changes that occur in the five major symptoms.The symptoms (extraction, light surface, pain, pruritus) are evaluated by the numerical values shown. 1...No symptoms, 2...Mild, 3...Moderate, 4
···heavy.

A control test was conducted before, during, and after the treatment.A range of 0 percent was used, that is, the change sound of the symptoms before, during, and after the treatment, and an index sound indicating the degree was used to set 1 on the second garment.

71': White No. 2 Based on the results of the second treatment using the total removal of the surface-unexplored combination of phlegm, five typical symptoms were observed at the end of the treatment (skin, -, light, pain, The majority of patients (pruritus)
It can be seen that in 95.3% of cases, the growth is reduced or almost completely gone (95.3% is the average of all patients with typical mild and no symptoms).

Side effects were only seen in 3 patients. Two patients had mild dry skin, and one patient had dry skin.

Regarding the efficacy of the combination soft If agent, 25.4% of patients responded to previous conventional treatment, while approximately 95% of patients showed good results after treatment using the formulation of the present invention. This was confirmed by Hanten.

The soft R compound is prepared according to the method of the present invention by preparing 9α-fluoro-11β, 21-dihydroxy-16α, 17α-isoglopylidenedioxy pregnathic 1,4-diene-
3,20-dione and 1,6-his[5-(4-chlorophenyl)-vig7=do]-hexane dihydrochloride or diglucone)'kl: 17 to 5
By mixing in a ratio of 0 and 1' excipients and/or phases commonly used in pharmaceutical manufacturing, an oil-water-type emulsion soft 11 groups can be obtained. It is made by a method of making it into an agent.

9α-fluoro-11β, 21-dihydroac-16α
, 1-ph α-ingropylidene dioxy pregnathic acid 1,
4-diene-3,20-dione and 1,6-bis[5
-(4-chlorophenyl)-piguanide]-hexanedihydrochloride, a soft tooth preparation containing both 9α-fluoro-11β, 21
-dihydroxy-16α,17α-ingropylidenedioxy-pregnath-1,4-diene-3,20-dione fine powder 0.05 to 0.25%, preferably 0.0 to 0.15% (final Soft, based on 4 simultaneous stop needles) to 1
,6-bis(5-(4-chlorophenyl)-biguanidecouhexane dihydrochloride (230 mesh)0
．． 5Z to 2.0%, and to this active ingredient mixture, add a separately prepared oil-in-water emulsion cartilage base little by little with regular stirring, and then homogenize the entire proboscis of the mixture. Conveniently, the oil-in-water emulsion cartilage base has a viscosity of at least 100 mPa' (about IO%
(based on the amount of fIK in the final cartilage wound), motomacrogol 25 and emulsified wax (British Pharmacopoeia, 1973).
, p, 91) k, 7111 at 1 when the mixture melts
It is prepared by heating and pouring the resulting melt into 60-65% water heated to 60°C.

When the soft meter 4i11 cools down to room temperature 1, mix with the softened base gold and preservative containing about 1 liter (based on the weight of the final soft and YT agent) and make it homogeneous. . It is preferable to use various benzoic acid derivatives as preservatives, such as p-hydroxybenzoic acid methyl ester and p-hydroxybenzoic acid 4m propyl ester.

9α-fluoro-11β, 21-dihydroxy-16α
, 17α-Inglobilite/Dioxygregner-1,
4-diene-3,20-dimene and 1,6-bis[
A soft Pf cup containing both 5-(4-chlorophenyl)-hycuanido]-hexane digluconate can be prepared by the method of the present invention, namely 1,6-bis[5-(4-chlorophenyl)-biguanide. ]-Hexane digluconate (preferably 1 or 20% commercially available) was added to water at about 60°C, which is necessary for soft-melting, f-pickling, and the oily mtn product produced by the above method was determined. Apply force to this water bath solution while stirring in a manner similar to that of Jυ, and completely cool the soft mass.
(c%) and then mixed with a fine powder of 9α-fluoro-11β, 21-dihydroxy-16α, 17α-impropylidenedioxy-Brebner-1,4-diene-3,20-dione to form a homogeneous mixture. Aokireru (manufactured by Ibukito BLJ).

EXAMPLES The invention will be explained in more detail in the following examples, but the present invention is not limited thereto. 5-(4-chloro7enyl)-hycuanito]-hexane dihydrochloride 1. O29α-
Fluoro-11β,21-dihydroxye6α,17α-isoglopylidenedioxypregna-1,4-diey-3,20-dione 0.12 Paraffin γ Mountain (,1′ space at least 100 mpa)
10.0? Setomarogol emulsifying wax [British Musical Phobia (B, P.), 1973.

p, 91, ] 2s, o
RF　D liquid *1〔-・Ngari National Pharmacopoeia (Pharm
acopoea Hungarfca) Vl.

p, 1314) 1. Of
Cetylstearyl alcohol 20. Of polyethylene glycol-1000-monocetyl ether 5.02**) Composition of storage solution: Propyl paraoxybenzoate 30. Or paraoxybenzamine methyl 70.0 P1 Nada thick alcohol-k (Spiritus concentrat
issimus) 900.0? The ingredients mentioned above? Using the following method, a soft
Old 1 - It can be said that: Barahui/Ura 10F and Setomarogol Emulsified Wax 252 were heated at 60°C'E in a water bath, and the resulting melt was heated in advance at 60°C. Heat water to 62.9F (11 degrees Fahrenheit), stirring periodically and slowly boiling. Continue stirring with an oil-in-water emulsion soft [1 unit] or a reed that can be heated to room temperature. 17 parts of the bath liquid containing all of the ingredients were homogenized with the cooled and strained base, the mixture was allowed to stand for 24 hours, and then mixed in three cylinders and stirred repeatedly. 1,6-bis[5-(4-chlorophenyl)-bicuanide]-hexane dihydrochloride 11 was ground to a total particle size of 230 mesh, and finely ground 9α-fluoro-11β, 21-dihydroxy-16α, 17α to ingloviridene dihydrochloride Oxypregna-1,4-diene-3,20-dione 0. If
'zMix this thoroughly. Finally, this mixture is mixed with the above-mentioned ointment base in small portions to homogenize the whole mixture to form a uniform ointment.

Example 2 Manufacture of soft f formulation 2 1.6-bis[5-(4-chlorophenyl oligo-piguanide)-hexane dihydrochloride 2.019α-fluoro-11β, 21-dihydroxy-16α, 1-fluoro-isopropylene Dendioxy-pregna-1,4-diene-3,20-dione 0.05!
i' Paraffin oil (viscosity at least 100 mPa) 1
0.0y Setomarogol emulsifying wax (B, P.

1973, p. 91) 25.0 ml preserved solution (Hungarian National Pharmacopoeia ■).

p, 1314) 1. Of distilled water 61.95 SF An ointment was prepared from the above ingredients according to the method of Example 1.

Fruit bs row 3 Soft -: Production of solid: 1.6-bis[5-(4-chlorophenyl)4/anido'-hexane dihydrochloride 1.5o29α-
Fluoro-11β,21-dihydroxy-16α,17α-isopropylidenedioxy-prefuner-1,4-diene-3,2o-dione 0.15S'Paraffin? '1IJ (viscosity at least 100mPa)
1 (1, OS' setomarogol emulsified wax (B
,P.

1973, p. 91) 25. Or preservation bath g (Hungarian National Mulberry Pharmacopoeia ■).

p, 1314) 1. (1' Distilled water 62.35S' From the upper ingredients, sieve 1゛Δ according to the method of Example 1 and prepare the entire product.

Example 4 European preparation: 1.6-bis[5-(4-chlorophenyl)-biguanide]-hexanedihydrochloride 0.50f9α-fluoro-11β,21-dihydroxy-16α,17α-isopropylidene dihydrochloride Oxy-pregna-1,4-diene-3,20-dione 0.20? Parafine? 11] (viscosity at least 100 mPa) I
0-02 Setomarogol emulsified wax (B, P.

1973, p. 91) 25. tJf preservation solution (Hungarian national medicine h'T3 method).

p, I 314) 1. O
f! Distilled water 63.3F
A softening agent is produced from the above ingredients according to the method of Example 1.

Example 5 Production of soft 1-4 ester: 20% water bath of 1.6-bis[5-(4-chlorophenyl)-bicuanido]-hexane digluconate 5go9α-fluoro-11β,21-dihydroxy -16α,17α-isopropylidenedioxy-prefuner-1,4-diene-3,20-dione 0. IP paraffin extraction (viscosity at least 100 mPa) 10
．． 0'? Setomarogol emulsifying wax (B, l).

1 (J73.p, 91) 2
5.02 Preservation solution (Hungarian National Pharmacopoeia ■).

p, l 314) 1. O
j' Distilled water 58.9F
Produce soft burrs from the above ingredients according to the following method: Chlorhexidine digluconate solution W 5 ml ”f
Heat to 60°C and add to 58.90°C of distilled water. The ingredients that completely form the oil phase are liquid paraffin 102 and cetomacrogol emulsified wax 252 gold in a water bath.
Heat in a CJ and slowly pour into the aqueous phase containing all of the chlorhexidine digluconate with constant stirring.

Continue stirring at 1 while the mixture cools to room temperature and homogenize with 12 volumes of stock solution and ointment. Add all of the above mixture to the mixture and make it evenly yellow to form a uniform ointment.

This is left for a total of 24 hours and then passed through a three cylinder mill.

l Chamberlain Applicant alkaloid begie seti jar patent application agent Patent attorney Akira Aoki Patent Attorney Kazuyuki Nishidate Patent attorney 1) Yukio Patent attorney Akira Yamaguchi

Claims (1)

[Claims] 1. 9α-fluoro-11β as an active ingredient. 21-dihydroxy-16α, 17α-ingrobiritin dioxy-bregna-1,4-diene-3,20-dione and 1,6-bis(5-(4-chlorophenyl)
- An anti-JN1 compound containing biguanide couhexane dihydrochloride or digluconate in a ratio of 1:1 to 1:50 and the same anti-inflammatory effect as Minami 1-
2.9α-Fluoro-11β, 21-dihydroxy-1
6α, 17α-Ingropylidene dioxypregnath
1,4-diene-3,2o-dione [):1,6-bis[:5-(4-chlorophenyl)-biguanidecouhexane dihydrochloride and digluconate in a ratio of 1:1 to 1:50 The active ingredient is combined with the excipients and/or carriers commonly used in pharmaceutical formulations by methods commonly used in the manufacture of all these pharmaceutical products. Dihydroxy-16α, 17α-ingropyritine dioxy~
Pregna-1,4-diene-3,2°-dione 0.05
Z stone 0.25 volume and 1.6-his [5-(4-
10 Lofenyl)-biguanidocouhexane dihydrochloride or digluco-) 0.25 to 2.5
% by weight of cartilage agents, syrups, tablets or other forms of punishment, and the anti-inflammatory action of the same. To the weir of stable local j-9r pharmaceutical formulations. 3,9α-fluoro-11β,21-dihydroxy-1
6α,17α-Ingropyridine dioxypregnator-1,4-diene-3,2+)-dione and 1,6-
Bis(5-(4-70lofenyl)-biguanide)-hexanedihydra chloride or digluconate is mixed with excipients and/or carriers commonly used in soft; 4. The manufacturing method according to claim 2, which comprises using 9α-fluoro-11β as a soft base.
, 21-dihydroxy-16α, 17α-lamprobiritin dioxygregner-1,4-diene-3,20-
The manufacturing method according to claim 2 or 3, which comprises using dione in the form of imitation powder. 5. When manufacturing all ointments, 1,6-bis-[5-(
4-chlorophenoxy)-biguanide]-hexane dihydrochloride used in powder form of 230 mesh, 1
, 6-bis[5-(4-chlorophenyl)-biyanido]-hexanecyclconate used in the form of a whole water bath! The manufacturing method described in Section 2, Reed, or Section 3, G46L8 of Tokigi F Claim.