DD216628A5 - PROCESS FOR THE PRODUCTION OF BIOLOGICALLY ACTIVE EXTRACTS - Google Patents

Abstract

A process is described for producing biologically active extracts from blood, blood plasma, milk, cartilage, placenta and muscle tissue, cereals, potatoes, fish, eggs, microorganisms such as yeast, or malt. The extracts obtainable according to the invention contain short-chain peptides. These extracts have interesting pharmacological properties and the like. strengthen d. Effect v. known circulation-promoting agents.

Description

: ·. - - ^l 1 - _t ..- '..;;

M / 24 222

Field of application of the invention ,

The invention relates to a process for producing biologically active extracts obtained from the tissue and body fluid of mammals or from cereals, microorganisms or eggs. The extracts obtainable according to the invention can be used in pharmaceutical _and cosmetic products and used as an additive to foods and stimulants.

Characteristics of the known technical solutions

The production of biologically active extracts from the blood of slaughter animals is known, cf. e.g. Swiss Patent 365,483. These extracts are essentially the well-water-soluble low-molecular components of the blood. They have a breathable effect.

Object of the invention

The aim of the invention is to provide a process for the preparation of active extracts with cell respiration-promoting effect, which can be obtained in higher yield and in a simple manner from readily available starting materials of animal and vegetable origin or from microorganisms. These extracts are intended to promote cellular respiration and metabolism in the organism in cosmetic and pharmaceutical compositions and as an additive to foods and stimulants.

ΐ r μ:

Presentation of the essence, the invention

The extract of the invention based on blood, blood plasma, milk, cartilage, placenta or muscle tissue, cereals (eg wheat, barley, rye or rice), eggs, yeast, fish, potatoes, microorganisms such as yeast or malt as starting material is obtainable by adjusting blood, homogenized cartilage substance, skimmed milk, homogenized placenta or muscle tissue, cereal bran, eggs, fish, potatoes, yeast or malt with water to a solids content of about 6 'to 14%, or blood plasma directly used-,

except when using malt, a lipolytic amylytic proteolytic enzyme mixture is added, which consists of approximately equal proportions of an enzyme derived from animal, plant, fungus and bacteria.

consists, ,

   , '/'

with constant stirring for some time at 30-60 ° C, then heated to deactivate the enzymes to about 90 ^P C and filtered hot,. , , concentrates the filtrate in a vacuum and subjects the concentrate to spray-drying,

the "powder obtained in the spray-drying suspended in an alcohol / water mixture, the suspension is allowed to stand for a few hours, then the supernatant filtered from the soil body, the filtrate concentrated or dries eiengt and optionally the product thus obtained in a water / alcohol Mixture dialyzed against water _x

Preferably, the dry matter content is adjusted to about 8-10%. ,

Breathable extracts, starting from malt, are also available according to the invention. In the case of malt, the proteolytic enzyme mixture is already present, so that a separate addition of such a mixture is not required, but is possible.

For the preparation of the active extract of malt according to the invention, any malt may be used, for example a commercial product. For example, germinated barley which has been dried is used to produce the extract. This is finely crushed, slurried with water in a weight ratio of about 1:10 to 1:15, heated slowly with stirring to 90 ^° C. over a period of 3-4 hours. Add filter aid, filter blank, concentrate in vacuo and dry in the spray tower. The subsequent processing consists in suspending in an alcohol / water mixture, leaving the suspension to stand , filtering off the supernatant solution from the soil body, concentrating the filtrate or concentrating to dryness and optionally dialysis in a water / alcohol mixture against water.

The extract according to the invention is a peptide-containing extract. The peptides have a molecular weight of about 300-5000 _r, preferably 300-3000, in particular 300-1500 and particularly preferably 300-1000.

According to the invention, not only extracts from a starting material but also extract mixtures of various starting materials can be obtained.

The product obtained as described above is called cell-i; breathable active ingredient fully effective. To improve its biocompatibility Can by dialysis when ^s you want to use the product eg for injection or infusion purposes. The extracts thus obtained contain all the low molecular weight, water-soluble constituents of the blood, the milk, the placenta and the cereal bran. In general, they have a cell respiratory-enhancing effect, which can be detected in the Warburg test. They can therefore be used as a circulation-compensating, wound healing-accelerating agent and for antagonizing oxygenase-inhibiting substances such as acetyl salicylic acid, flufenamic acid, nephemic acid or indomethacin: in therapy. It has also been found that they antagonize the toxic effects of glycolysis inhibitors, such as phosphonates, eg phosphonoacetic acid or arabinofuranosyladenine or its 5'-phosphate, and act antivirally and analgesically. In addition, they can be advantageously used in cosmetics, for example for the preparation of skin creams and lotions.

It has surprisingly been found that the product obtainable according to the invention strongly antagonizes a number of toxic effects. In mice, this can be done, for example, on Pentoxify11 in 2eigen. A dose of pentoxifylin of about 300 mg / kg, ip, is normally fatal to a mouse. However, if the product according to the invention is administered intraperitoneally or intravenously in a DoS ¹ IS of about 400 mg / kg about 30 minutes beforehand, this results in a clearing effect, which results in a corresponding reduction in the death rate. The determined in this way. Activities of the extracts according to the invention are summarized in the table below and compared with a known respiratory active substance:

Protective substance (400 mg / kg) Mortality protective effect

by 300 mg / kg pentoxifyl 1 in

.. ·.%. %

Control: 0.9 % NaCl solution 100 0

Blood extract according to Example 1,

¹ ^ - °

Milk extract according to Example 2,

i.p. 20 80

Keizenkleieextrakt

according to Example 5 30 ·, 70

Blood extract according to the

CH-PS.365 483, i.p. 80 20

The known reference extract:> is an infusion preparation based on deproteinized calf blood, which is administered in severe cerebral circulatory and metabolic disorders as well as peripheral arterial and venous circulatory disorders and burns.

The above-mentioned extracts were intraperitoneally administered as 4% solutions, and about 30 minutes later, the toxic dose of pentoxifylline in 3% solution was also intraperitoneally administered. The control was a 0.9% NaCl solution. The volume of administered solutions was kept constant, always 0.1 ml / 10 g mouse. The invention. Extracts are fully effective, even without additional dialysis.

Further investigations in this direction confirmed that the combination of a breath - enhancing natural active substance of the type described above with a circulation - promoting active substance, the therapeutical index of the perfusion - promoting active substance can be considerably increased.

As a circulation-promoting agent used z. B.

i) the 2,5-Pihydroxibenzolsulfonsäure cal ciumsalζ, also called Calciumdobesilat;

ii) a 3,7-pihydro-3,7-di-C ^. _4- alkyl -1- (5-substituent)

1) - 1H-purine-2,6-dione of the formula Ir

wherein Alk is the same or different straight or branched Niedrigalkylres te with 1 to 4

C atoms and 15

R is a -C-CH ₃ or -C ₂ H ₅ -ReSt;

iii) a pyrazolo [3,4-d] pyrimidine of all formula II:

^: νΛ

wherein

1 2 ''

R and R, which are the same or different, are for

a Η-atom or the radicals C.-Cg-AlkyT, Cp-Cg-alkenyl, C ₄ -Cg-alkylcarbonylalkyl, R and R, however, can not be simultaneously .ei η 'Η atom and

_A for a group

35

or I / ^IV

where _R 3 is _an Η-atom or C ₁ -C ₄ -alkyl and

_R 4 is an .Η atom. G ₁ -C ₆ -AUyI or-C ₂ -Cg-alkenyl means "preferably

R ^ and R ^{3 are} methyl or ethyl and R ^{2 is} -CCH ₂ ) ₄ -CO-CH ₃ .

iv) a pyridone of formula III:

wherein R is a -C-CH ₃ , -C ₂ H ₅ or -C ₂ H ₄ OH radical; q

y) or nicergoline, vincamine or dipyridamole.

Preferred compounds of the formula I are

PentoxifyllineundPentifylline. IO

The active ingredients of paragraphs!), Ii) and v) are known, cf. z. 9th edition, No. 3406, 6927, 6931, 9638, 6310 and 3366. · The Merck Index.

The pyrazole-opyrimidines of general Formula II are prepared by using a 4-hydrazine acidase of al-1.

(Ha) 25

1 ? * 1

wherein R, R and R have the meanings given above, with Phosphoroxychl orid and dimethylformamide in a conventional manner, for example after

- 1

methods given in DE-AES 1186466, is reacted. Advantageously, the 4-hydrazine acid * c is introduced into a cooled mixture of phosphorus oxychloride and dimethylformamide. When the 4-hydrazino acid has been completely introduced, the reaction mixture is allowed to warm to room temperature. When adding ice, the desired product precipitates.

..- .. ''.,. , y 7 '

- If a aer radicals R or R represents a Alkylcarbonylalkylrest, one may advantageously proceed by reacting a corresponding 4,5,6,7-tetrahydro-4,6-dioxo-pyrazolo [3, 4-d) pyrimidin with alkoxylated a o, ω '-Di broma 1, which is reacted Ur-Bromalkylderivat reacted with acetoacetic ester and the resulting product subjected to a Ketonspal device. For example, by reacting 7-ethyl-4,5,5,7,7-tetrahydro-1-methyl 1-4, 6-

20 diboxo-1H-pyra, zolo {3,4-d] pyrimidine with 1,3-dibromopropane, the 5- (3-bromopropyl) -7-ethyl-4,5,6,7-tetrahydro-1-methyl- 4, 6-dioxo-lH-pyrazolo13,4-dlpyrimidine, from which the reaction is reacted with acetoacetic ester and subsequent ketone cleavage gives the 7-ethyl-4,5,6,7-tetrahydro-imethyl-4,6-dioxo On the other hand, the alkylcarbonylalkyl radical can also be obtained by reacting a 4,5,6,7-tetrahydro-4,6-dioxo For example, the 5-oxo-n-hexyl radical may be introduced through 1-chloro-hexanone-5, for example, as an alkali metal salt, with an alkylcarbonylalkyl halide, preferably a chloride.

The pyridones of the formula ΠΊ are known from the German patent applications P 22 28 289 and P 22 25 229.

'

Examples of preferred pyrazolopyrimidines of the formula

II are:

₇ _ _n . _Hexyl- 4,5,6,7-tetrahydro-1,5-dime-1, 4, 6-di, oxo.

itf-pyrazolo [3,4-d] pyrimidine (mp 111 ° C); ₅ _ _n _ _Hexy 1-4, 5,6,7-tetrahydro-1,7-di methyl-4,6-di 0x0

iH-pyrazolo [3,4-d] -pyrimidi η; "7_i_butyl-4,5" 6,7-tetrahydro-1, 5-dimethyl-4,6-dioxo- _1H- pyrazolo1o [3,4-d] pyrimidine;

2-ethyl-5-n-hexy1-4,5,6,7-tetrahydro-7-methyl-4,6-d ₁ oxo

2H-pyrazolo [3,4-d] pyrimidine (m.p. 110 ⁰ C.); Γ

2-n-butyl-7-n-hexyl-4 _> 5 _s 6 _s 7-t _e trahydro-5-methyl-4,6-

dioxo-2H-pyrazolo [3,4-d] pyrimidine (mp 67 ° G); 4,5,6,7-tetrahydro-5-methyl-4,6-dioxo-7- (5-oxo-n-hexyl) -

2H-pyrazolo [3 _s, 4-d] pyrimidine; _

_4> 5 _i6 , 7-tetrahydro-1-methyl-4,6-dioxo-5- (5-oxo-n-hexy1) -

3-n-propyl-1 H -pyrazolo _I 3,4-d] pyrimidine;

5-n-hexyl-4,5,6,7-tetrahydro-2,7-dimethyl-4,6-dioxo-2H-pyra-2-ol [3,4-: d] -pyrimidine (m.p. 73-757C); 2-n-butyl-5-n-hexyl-4,5; 6,7-tetrahydro-7-4,6 TnethyV

_diox o-2H-pyrazolo-i3,4-d3pyrimidin (m.p. 88-90 ⁰ C.);

2,5-di-n-hexyl-4,5,6,7-tetrahydro-7-methyl-4,6-dioxo-

2H-pyrazoToi3,4-d] pyrimidine (m.p. 80-81 ⁰ C.); 7-n-HexyV-4,5'.6,7-tetrahydro-5-methyl-4,6-dioxo-2H-

pyrazolo D, 4-xd] pyrimidine (mp 159-161 ⁰ Cj ₇ _ _n _Hexyl-4,5,6,7-tetrahydro-2,5-dimethyl-4,6-dioxo)

2H-pyra ₂ oTo [3,4-d] pyrimidine (m.p. 109-110 ⁰ C.);

2-i7-di-n-hexyl-4,5,6,7-tetrahydro-5-methyl-4,6-ClIOxO-ZH-

_P yra oloi3,4 _2-d] pyrimidine (m.p. 96-97 ° C.); 4.5,6,7-T etrahydro-2-m _{e-4 s} thyr 6-dioxo-7- (5-oxo-n-hexyl) -2H-pyra2olo-13.4-d Ipyrimidin;

7-ATlyl-2-n-hexyl-4, 5,6, 7-tetrahydro-1,5-dimethyl-4,6-dioxo-2H-pyrazolo [3,4-d] pyrimidine; 4, 5, 6, 7Z tetrahydro-3, 5-dimethyl-7- (2-methylbutyl) -4, 6-

'' '' '' '

dioxo-IH-pyrazolo [3,4-d] pyrimidine; 4,5,6,7-tetrahydro-1, 5-dimethyl- 7- (2-methylbutyl ) -A , 6-dioxo-1H-pyrazolo [3,4-d] pyrimidine; 7-n-hexyl-4,5,6,7-tetrahydro-5-methyl-1,4,6-dioxo-2-n-propyl-T2H-pyrazole o- [3,4-d] pyrimidine; A , 5,6,7-tetrahydro-1, 5-dimethyl-4,6-dioxo-7- (5-oxo-nhexyl) -1H-pyrazolo! O [3,4-d] pyrimidine; 2-ethyl-7-n ⁱ -hexyl-4, 5, 6, 7-tetrahydro-5-ethyl-ethyl-4,6-dioxo-2H-pyrazolo [3,4-d] pyrimidine (mp 96-97 ° G) ; 5-n-hexyl-4, 5,6,7-tetrahydrp-7-methyl-4,6-dioxp-1H-pyrazolo o [3,4-d] pyrimidine (mp 138 ° C); -

3-Ethyl-5-n-hexyl-4 ', 5, 6, 7-tetrahydro-1, 7-dime-thy! -4, 6- _f * dioxo-1H-pyrazolο (3, 4-dJpyrimidin; 5-n-hexyl-4,5,6,7-tetrahydro-3- (3,4,5-tr imethoxypheny V) -1 , 7-dimethyl-4,6-dioxo-1H-pyrazole o [3,4, d] pyrimidine ; ., -7 -i-butyl 1-4,5,6,7-tetrahydro- 5-methyl-4, 6-dioxo-1 H-pyrazolo I3 "i4-d] pyriraidin (m.p. 204 ⁰ C.), 4, 5 _s 6,7-tetrahydro-3- (2-hydroxyethyl) -4, 6-dS * oxo-5- (3-.

ο χ ο b υ ty 1) - 2 H - py r a ζ ο 1 ο 13, 4 - d) py r i m i d i η. 25

The breath-releasing excipients obtainable according to the invention can therefore be used advantageously in medicaments containing one or more of the circulation-promoting active ingredients mentioned above, optionally in a conventional solid or liquid drug carrier. ν

 The extracts obtainable according to the invention can also be combined with CaI cium antagonists. It has now surprisingly been found that the pharmacological effects of calcium antagonists can be increased by the use of the extracts according to the invention in a synergistic manner.

This can be demonstrated by the improvement of the protective effect against damage of retinal functions by allyl alcohol.

I. ¹ . , ,

The retinal damaging effect of allyl alcohol can be demonstrated by si.ch with the help of the electroretinogram of the retina. The electroretinographic detection of this damage corresponds to that of GAURI et al. in DOCUMENTA OPHTHALMOLOGICA; The Hague 1977, pages 335 to 340 and in "Der Augenspiegel", Issue 9, 1979 pages 1 to 16, described methodology.

To study the injurious effect of allyl alcohol, dark adapted female NMRI mice were given 100 mg / kg i.p. 25 minutes prior to urethral anesthesia.

ι allyl alcohol injected. The animals were then connected to an electroretinogram (ERG) device within 5 minutes. For this purpose, a silver chloride wadding electrode 'was placed on the corneal surface of the experimental animals and a second silver needle electrode inserted retrobulbar in the eyelid angle of the eye of the experimental animals. Registration of the ERG-b wave potentials was at full intensity. In this way, the maximum b-wave potentials were determined.

-H-

To test the protective effect, the dark-adapted animals first received the virus solutions i.p. injected. 30 minutes later, allyl alcohol was administered 100 mg / kg i.p., and an additional 25 minutes later the animals were anesthetized with urethane and connected to the ERG device within 5 minutes, as usual. , .

The results obtained are summarized in the following table.

Improvement of the protective effect by the combination of Ca-antagonists with the extracts according to the invention against the allyl alcohol damage shown on the electroretinograrnm of the mouse

Pretreatment and drug maximum b-waves

-.  '..-.   , potentials

Control (urethral anesthesia) 1 326

'..' ... , -

Damage with allyl alcohol 365,

Nimodepine (A) 10 mg / kg p.o. 707

Bovine blood extract (B) / ·

10 mg / kg i.p. Invention 690

Combination of (A) and (B) "1 503.5 diltiazem (C) (10 mg / kg i.p.) 58B

Combination of (B) and (C) ^βι 1 177

These results show that the animals to which an extract obtainable according to the invention has been administered together with a Ca antagonist are almost completely protected against the damage caused by allyl alcohol, while the animals treated with only one active ingredient are only very little protected.

The extracts described according to the invention have a surprisingly advantageous antiviral effect, even without other therapeutic additives. Typical herpes diseases (herpes zoster, genitalis, labialis andcorneae) can be treated very successfully with it, surprisingly this effect is retained on oral administration.

The pharmaceutical compositions prepared with the extract obtainable according to the invention may be administered parenterally, preferably in the form of aqueous solutions, with or without solubilizers or orally in solid or liquid formulations, e.g. be applied as tablets, dragees or aqueous solutions. If desired, they may also be used as locally applicable preparations, e.g. be prepared as an ointment, gel, powder or lotion. They may also be formulated as inhalation preparations, e.g. as a spray.

In view of the fact that circulation-promoting agents are generally used over a longer period of time (usually several years), the reduction of the toxicity of these compounds by the combination according to the invention is a significant enrichment of human therapy

 35

The breathable extracts obtainable according to the invention can be used as an additive to beer and other alcoholic beverages. Particularly useful is the use of an amount of 0.2 to 10 wt .-% of breathable extract, based on the total weight of the respective food and stimulant. '

Especially useful are additives in an amount of 0.5 to 7 wt - . %, In particular 1 to 4 wt .-%.

In foods and stimulants are often found components that normal cell respiration and den.Stoffp. change adversely affect, for example

O. oxygenase inhibitors and glycolysis inhibitors. Often foods are offered which salt unwanted traces of heavy metal and other toxic substances. These substances must be eliminated by active oxygen 2Q from the organism.

For example, in the case of short-term and, in particular, prolonged consumption of alcohols, the formation of aldehydes, in particular of acetaldehyde, which are detrimental to the organism, takes place.

For the detoxification of aldehydes the organism oxydases are available, which degrade the aldehydes using oxygen. By enrichment of breathable substances in food and foodstuffs the detoxification important for the organism can be achieved. ·

The use of the extract obtainable according to the invention leads to such a detoxification of the organism. The toxic effects of toxic substances in the food and drink are prevented or compensated by this use.

There are already substances in the beer which, to a certain extent, reduce the above toxic effects. The use according to the invention of the breathable extracts as an additive to beer leads to a substantial increase in the detoxifying action of the beer.

It is believed that the cellular respiration and metabolism-promoting action of the extracts obtainable in the present invention is based on supporting the energy-providing processes in the organism. The said use leads to unexpectedly advantageous nutritional-physiological effects of the type described above.

,

The following examples serve to further illustrate the ^v Erfiη dung. .,

example 1

-. · Heavy blood from the slaughterhouse is vom

• Plasma is removed and diluted with water to a solids content of about 30% by weight. 10 1 .this -.- Bl utes are 0 ^to about 10 g of amy ly.ti see-Xipo "1y ti sehenproteolytischen Enzynigemisches, for example a mixture of equal parts of pancreatin, papain and two derived from yeast enzymes. Under uniform, slow agitation is heated to 35-38 C ^c. With continuous, uniform stirring keeping this temperature level for about 1 hour, then heated further to about 53-57 ° C, holding at this temperature level for about 2 hours, and finally outputs a Fi1terhi1fsmittel to heated to about 90 ° C. and filtered through a filter press while hot The resulting clear filtrate is concentrated in vacuo to about 30 % solids and then spray dried The resulting powder is suspended in a 70/30 alcohol / water mixture If the suspension is allowed to stand for about 8-12 hours, the undissolved constituents settle out, and the clear supernatant solution is filtered, ie vaporizes the alcohol and subjects the residue to spray drying.

The product thus obtained is colorless and suitable for the

According to the purposes of the invention fully usable. To improve the body compatibility, this product can be further purified by dialysis. Preferably, a 70/30 alcohol-water mixture is dialyzed against water. The product purified by dialysis can be readily used for injection and infusion purposes.

Example 2 . , .

10 Ί skimmed fresh milk with 5g pancreatin each

  '' '

and papain and two enzymes derived from fungi and bacteria. With constant slow stirring, one heats to about 36-38 ° C and remains at this temperature level for about one hour. Gradually, _

.coloured the milk and you get a bright solution.

· "(> Now, the temperature is maintained at about 54-56 ° C, remains" with constant stirring at this temperature level, then outputs a Fi1terhi1fsmittel to, a _heated; uf about 90 ⁰ C and filtered through a HEI3 Fi1terpr.esse. ·

The clear filtrate is z. B '. in a Wi'datnd-Fa-Strom-15-. ' · "

evaporator concentrate and dried in a spray evaporator. The product thus obtained is suspended in an aqueous alcoholic solution (about 80% by weight ethanol / 20% by weight water), this suspension is then allowed to stand for about 12 hours, filtered, and the mixture is removed

Alcohol and the residue is again subjected to spray drying. This gives a colorless, · suitable for inventiveness ί purposes in accordance with product. For further purification, it can be subjected to dialysis. ''V

· - · '; ^ ^; ·

^'Be ^ 3 game

1.6 kg skimmed milk powder are dissolved cold in 20 l demineralised 3C water. 'Nach.mehrstündigem. Stirring gives a homogeneous solution. This is further processed analogously to the information of Example 2. This gives a colorless fully active product.

, '' ν .. ''. ' , v: -v ^:. ..>.

at game 4

& Placental tissue from slaughtered animals, in a Homogenisa tor ze rk 1einert, mi water t 'is diluted and adjusted to a solids content of about 10 wt .-%. The further processing takes place according to the instructions of Example 1. This gives a / colorless, fully effective product.

..ο .. '. '. '.' , , ".

Example 5 -

10 kg of wheat bran are finely ground and suspended in 100 liters of distilled water. In this state, uranium is the enzyme mixture of Example 1 and heated with continuous stirring to a maximum of 35 ° C. One keeps the temperature constant for one hour and raises to 55-60 ⁰ C * again becomes 2 hours at this temperature

stirred and then heated to 90 °, with Filter-20

Earth offset and clarified by a filter press. The solution is concentrated in vacuo, mixed with alcohol / water mixture (70/30) and separated from the precipitate. After evaporation of the alcohol, the solution becomes

spray dried.

The product according to the invention can be standardized in terms of its biological activity.

Example 6

(Extract from 'Malt'). · · · ·. Manure ₍ grind 10 kg of germinated and dried barley and suspend in 100 liters of cold distilled water.) Then marr with constant stirring in the course

from 3 1/2 hours to a final temperature of about 35

• 90 ° C. It is mixed with filter aid and clarified by a filter press. The solution obtained is concentrated in vacuo, with alcohol / water mixture (70/30).

added and separated from the precipitate. After evaporation of the alcohol, the solution is spray-dried.

Example 7

10 ~. .10 kg of yeast is suspended in 100 1 of distilled water, the cells are destroyed by ultrasound, the enzyme mixture described in Example 1 is added with constant stirring and the temperature is raised slowly to a maximum of 37 ^° C. and maintained at this temperature for about 1 hour. Thereafter, the temperature is raised to 55 to 60 ⁰ C and keeps 2 hours as usual at this temperature. Priority filter aid were added, the mixture was then heated to 90 ⁰ C und.behandelt the klareFiltrat as in the other examples described to obtain the active product.

Example 8

Homogenise 10 kg of boiled eggs together with the skins, dilute with water. 100 kg, treat with enzymes at elevated temperature, ^{v to} obtain a clear filtrate. Purify by precipitation with etherol water (70:30).

35

- «22 -

Be i s ρ ie 1 9

"" (- '.

 5 Treat 10 kg of fresh eggs as described in Example 8 to obtain the active product.

Example 10 .

5 kg of potato remainders (shells), obtained as a waste product from the potato industry, are slurried with 50 l of water and homogenized mechanically. The mixture is boiled 30 minutes, then cooled to 30 ° C, the enzyme mixture is added and may aggravate the temperature to 37 ⁰ C. This temperature is maintained one hour and then the temperature is raised for 2 hours at 60 ⁰ C. is then added filter aid · and steam the mixture. Continue as described above to obtain an active extract.

applications

1) Equal amounts of Calciumdobesilat and Pentoxyfylline were dissolved in an approximately 0.02 to 0.6 2 -year aqueous extract of blood according to Example 1. The single dose contained about 60 to 100 mg dobesilate, 25 to 100 mg pentoxyfylline and 1 to 100 mg

Blood extract.

A preparation of analogous composition may be prepared by mixing the appropriate proportions of solid and a conventional pharmaceutically acceptable carrier. Analogous preparations may be made from the above-mentioned blood extract and the other circulation-requiring substances referred to in the present application

Active ingredients such as vincamine, nicergoline, one of the pyrazolopyrimidines or pyridones referred to here are made. For the preparation of the preparations according to the invention, about 1/4 to 1/10 of the usual therapeutic dose of the respective active ingredients is used in combination with the respiratory-enhancing natural active ingredient described here

 .

2) Solution for injection: Pentoxifyl1 in 40 mg of blood extract 20 mg

Isotonic NaCl-, ·, -, p- solution ad 5ml

ι '' · · '

3) Solution for infusion: Vincamine 800 mg Blood extract 3000 mg 10% aqueous

Glucose solution ad 11

4) 1000 tablets:

Pentifylline 100g

Blood extract 20 g

Carrier mass for.

Tablet 80 g

5) anti-herpes remedy ^

Blood extract 5g

Isopropanol / H ₂ O 6Ο / 4Ο ad 100 ml

Claims (5)

invention claim »/>, C / cffi se he & * 're -_y 1. Process for the preparation of extracts based on blood, blood plasma, milk, cartilage, placenta and muscle tissue, cereals, potatoes, fish, eggs, microorganisms such as yeast, or malt of starting material, characterized in that blood, homogenized cartilage, skimmed milk, homogenized. Placenta or muscle tissue, cereal bran, eggs, fish, potatoes, yeast or malt with water at _N, a solids content of about 6 to 14 % sets, or blood plasma used directly, adding, except when using malt, a 1-dipolytic-amylyletic-proteolytic enzyme mixture consisting of approximately equal proportions of an animal, plant, fungus and bacterial enzyme, with constant stirring for some time at 30-60 ⁰ C, then heated to about 90 ⁰ C to deactivate the enzymes and filtered hot, the filtrate is concentrated in vacuo and the concentrate is subjected to spray-drying, the powder obtained in the desiccation suspended in an alcohol / water mixture, the suspension is allowed to stand for several hours, then the supernatant solution filtered from the bottom of the body, the filtrate concentrated or concentrated to dryness and optionally the product thus obtained in a Alcohol / water mixture dialyzed against water; and extract mixtures of extracts of the various starting materials above. 2. The method according to item 1, characterized in that the enzyme mixture used is a mixture of approximately equal proportions of pancreatin, papain, PiIzprotease and bacterial protease. 3. The method according to item 1 or 2, characterized in that one uses an approximately 70/30 alcohol / water mixture for suspending the product obtained after the first · constriction * - process and thereby adjusting to a solids content of about 10%. 4. The method according to item 3, characterized in that an 80/20 alcohol / water mixture is used in the preparation of the extract and the resulting precipitate is resuspended in a 70/30 alcohol / water mixture and the clear Alkohol1ösung concentrated to dryness , 5. The method according to any one of items 1 to 4, characterized in that one uses in dialysis an approximately 70/30 alcohol / water mixture.