JPS59134727A - Biologically active extract and manufacture - 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 The present invention relates to mammalian tissues and body fluids.1. The present invention relates to biologically active extracts obtained from cereals, microorganisms or eggs and to pharmaceutical and cosmetic media containing all of this extract.

A process for the preparation of the extract and its application as an additive to foodstuffs and luxury foods is also an object of the present invention.

The production of biologically active extracts from the blood of slaughtered animals is known (see, for example, Swiss Patent No. 3.55,483). In these extracts, the low molecular weight components of blood, which are well soluble in water, are essentially problematic. These have a respiratory promoting effect.

The present invention is characterized in that a biologically active extract having a cell respiration-promoting effect can be obtained in high yield in a simple manner from readily available raw materials of animals and plants. Extracts promote the cellular respiration and metabolism of living organisms in cosmetic and pharmaceutical media and as additives to food and luxury products.

blood, plasma, milk, cartilage material, placenta or muscle tissue, cereals (e.g. wheat, barley, rye or rice) according to the invention;
Extracts from microorganisms such as potatoes, fish, eggs, yeast, or malt can be used to extract blood, homogenized cartilage, skimmed milk, homogenized placenta or muscle tissue, grains, eggs, etc.
fish, potatoes, yeast, or malt by adding water to adjust the solids content to about 6 to 14 parts, or directly using blood plasma or, if malt is not used, from animals, plants, fungi, and bacteria. To each of the extracted enzymes, a mixture of lipolytic, amylolytic, and proteolytic enzymes was added, and the mixture was stirred uniformly for several hours at 30-6 Ll'C, and then heated to approximately 90°C. The filtrate is concentrated in vacuo, the concentrate is spray-dried, the powder produced by spray-drying is suspended in an alcohol/water mixture, and the suspension is left for several hours. After standing, the supernatant is filtered from the solids, the filtrate is concentrated or IAm to dryness, and if desired the product is dissolved in a water/alcohol mixture and dialyzed against water, preferably dried. This can be obtained by adjusting the substance content to about 8 to 10.

According to the invention, a respiratory active extract derived from malt can also be obtained.

In the case of malt, since there are proteolytic enzymes, such a mixture does not need to be added separately, but may be added.

For producing the active extract according to the invention from malt, it is possible, for example, to use commercially available malt.

For the production of extracts, for example, dried ones may be used, but
Use sprouted barley. This is powdered, suspended in water at a weight ratio of about 1:10 to 1:15, and heated to 90'C for 6-4 hours with gentle stirring. Filter clear with filter aid, concentrate in vacuo and dry in a spray tower. Finally, suspend in an alcohol/water mixture, leave the suspension, filter the supernatant from the solids, concentrate or concentrate the filtrate to dryness and, if desired, add the alcohol/water mixture. Dialyze against water.

The extracts of the present invention based on blood, plasma, cartilage material, milk, placental tissue, cereals or malt relate to peptide-containing extracts. The peptide has a molecular weight of about 600 to 5000, preferably 600 to 6000, especially 600 to 1500 and more preferably 600 to 1000.

The present invention encompasses not only extracts from one raw material, but also extraction mixtures from different raw materials.

The products obtained by the above-mentioned method are highly effective as cellular respiration promoting agents. Its biocompatibility can be improved by dialysis and the product is used for example for injection or infusion. The extracts thus obtained all contain low molecular weight, water-soluble components of blood, milk, placenta and grain bran. Usually these extracts have a cellular respiration-promoting effect, which has been proven in the Warburg test and test-proven. It can be used as an antagonist of oxygenase inhibitors such as nefuenamic acid or indomethacin. These include phosphates such as honufonoacetic acid or arabinofuranosyl adenine or its 5'
- It has also been revealed that it antagonizes the toxic effects of glycolyse inhibitors such as phosphoric acid, and has antiviral and analgesic effects. Furthermore, the extracts according to the invention can be preferably used in the production of cosmetic products, such as skin creams and lotions.

It has surprisingly been found that the products of the invention antagonize a range of toxic effects. In experiments using mice, this can be demonstrated with pentoxifylline, for example. about 6
The intraperitoneal administration of pentoxifylline at 90 mg/day is
Usually a lethal dose for mice. However, if the product of the invention is administered intraperitoneally or intravenously at a dose of about 400 m9/90 minutes prior to about 60 minutes, a protective effect occurs and the corresponding mortality rate is reduced. The effects of the extract of the present invention thus found are summarized in the table below and compared with known respiratory promoting agents.

Protective substance (400 my/kg) Pe/Toxy Protective effect Filin 600 m9/to 9 Mortality rate due to Chi Control: 0.9 Chi Salt solution 100 0 Example 1
Blood extract according to Swiss Patent No. 365483, intraperitoneal 0 100 Milk extract according to Example 2, intraperitoneal 20 80 Wheat extract according to Example 5 50 7° Blood extract according to Swiss Patent No. 365483, intraperitoneal 80 20 Known comparative extraction The product is an injectable product made from deproteinized calf blood and is intended for use in cases of severe cerebral blood flow and metabolic disorders, such as peripheral arterial or venous blood flow disorders, or burn injuries.

The above extract was administered intraperitoneally as a 6° solution of pentoxifylline as a toxic substance, and then intraperitoneally as a 4% solution.

A 0.9% saline solution was used as a control. The volume of the administration solution was kept constant, always 0.1 ml/10 i mouse. The extract of the present invention has sufficient effects even if it is not further purified by dialysis.

Further studies in this regard have shown that by combining a respiration promoting natural agent of the type described above with a blood flow promoting agent, the therapeutic index of the blood flow promoting effect can be significantly increased.

Examples of blood flow promoting substances include +)2. Calcium salt of s-dihydroxybenzenesulfonic acid, also called calcium dopesylate, 11) Formula ■ 1 Alk (where alk is a straight or branched chain having from 1 to 4 carbon atoms, which are the same or different) Lower alkyl residue, Ri'j: -0-0)13 or -c2H
6,7-sihydro6,7-di 0
N-4-alkyl-1-(5-substituted)-1H-purine-
2,6-Sion, 111) General Formula II 2 [In the formula, R1 and R2 are the same or different, hydrogen atom or alkyl of al-08, alkenyl of 02-08,
Although it is a C4-C8 alkylcarbonylalkyl group,
R1 and R2 cannot be hydrogen atoms at the same time, and A is a group 3 (wherein R3 is a hydrogen atom or an alkyl group of cl-0, R'it is a hydrogen atom, an alkyl group of C1-06 or ( 32-C6 alkenyl), preferably R1 and R3 are methyl or ethyl and 6D, R2 is -(OH2), -Co-OH, pyrazolo[3
, 4-a) Pyrimidine iV) Formula ■ ■ (OH2)2-diR (wherein, R is 10-0H3, -02H5 or 102H
pyridone (representing a group 50H), or ■) nicergoline, vincamine or dipyridamole,
is used.

Preferred compounds of formula I are pentoxifylline and pentifylline.

The active substances in sections +), +r) and V) are known and 6D, e.g. Merck Inaex J, 9th edition, 64th edition.
06.6927.6951.6938.6310 and 6666.

Pyrazolokirimicin of general formula II has general formula ■a (wherein R1, R2 and R3 have the same meanings as above)
4-hydrazinouracil is prepared by reacting phosphoryl chloride with dimethylformamide in a known manner, for example as described in German Patent Application No. 1 186 466. Preferably, the 4-heazinouracil is added to the cooled mixture of phosphoryl chloride and dimethylformamide. After adding 4-hydrazinouracil,
The reaction mixture is allowed to return to room temperature. Addition of ice precipitates the desired product.

When one of the residues R1 or R2 is an alkylcarbonylalkyl group, the corresponding 4,5,6.7-tetrahydro-4,6-thioxobirazolo[6°4-d]pyrimidine is ω,ω It is preferable to alkylate with a '-sideromalkane, react the resulting ω-bromoalkyl derivative with an acetoacetate, and decompose the product into ketone. For example, 7-ethyl-4,5,6, Fuchitra Hero 1
-half-methyl-4,6-thioxo-1H-pyrazolo[6
, 4-a) Reacting pyrimidine with 1,6-dibromopropane to produce 5-(6-bromoprogyl)-7-ethyl-4
, 5,6, futhitrahydro 1-methyl-4,6-thioxo 1H-pyrazolo[I3,4-d]pyrimidine, reacted with acetoacetate, and finally ketone decomposed to give 7-ethyl -4,5,6,Fuchtrahydro-1-methyl-4,6-shioquin-5-
(5-oxo-n-hexyl)-1H-pyrazolo[3,
4-da pyrimidine is produced. 4, 5, 6. "7-chitrahi-P-rho 4,6-sioquin-pyrazolo [3,4-d
] Alkylcarbonylalkyl groups can also be introduced by reacting a pyrimidine, preferably a sodium salt, with an alkylcarbonylalkyl halide, preferably a chloride.

For example, a 5-oxo-n-hexyl group is introduced by 1-chlorohexan-5-one.

Pyridone of the formula ■ is described in German patent application P 2228289
No. and P2225229.

Examples of the pyrazolopyrimidine of formula (1) above include the following.

7-n-hexyl-4,5,6,7-chitrahirozu,
5-dimethyl-4,6-thioxo 1H-pyrazolo[3
,4-cll-pyrimidine (m,p,'l11''
C), 5-n-hexyl-4,5,6,7-titrahy 10-1
,7-dimethyl-4,6-thioxo 1H-pyrazolo[
3,4-d]-pyrimicin, 7-inputyl-4',
5,6,7-tetrahydro-1,5-zomethyl-4
,6-thioxo 1H-pyrazolo[3,4-a-)-pyrimidine, 2-ethyl-5-n-hexyl-4,5,6
゜7-Titrahydro-7-methyl-4,6-thioxo-2H-pyrazolo-[3,4-a:]pyrimidine (m, p
, '110°C), 2-n-'butyl-7-n-hexyl-4,5°6.
7-chitrahero 5-methyl-4,6-thioxo 2
H-pyrazolo-[3,4-a]pyrnomidine (m, p,
67°C), 4.5,6.7-tetrahydro-5-methyl-4,6-
Thioxo 7-(5-oxo-n-hexyl)-2H-
Pyrazolo-[3,4-d)pyrimidine, 4,5,6,7-tetrahydro-1-methyl-4,6-
Dioxo-5-(5-oxo-n-hexyl)-3-n
-Propyl-1H-pyrazolo[6°4-d]pyrimidine, 5-n-hexyl-4,5,6,7-tetrahydro-2
, fucymethyl-4,6-thioxo-2H-pyrazolo[
3,4-d]pyrimidy (m, p.

73-75°C), 2-n-butyl-5'-n-hexyl-4,5°6-1
7-thitrahy10-7-methyl-4,6-thioxo2
H-pyrazolo-[3,4-d]pyrimidi7 (m, p,
88-90°C), 2.5-di-n-hexyl-4,
5,6,7-titrahydro-7-methyl-4,6-dioxo-2H-pyrazoDC3,4-dlpyrimidy (m
, p.

80-81°C), 7-n-hexyl-4,5,6,7-tetrahydro-5
-Methyl-4,6-thioxo2H-pyrano[3,4
-a, ]pyrimidi 7 (m-p, 159-161°C), 7-n-hexyl-4,5,6,7-tetrahydro-2
,5-dimethyl-4,6-thioquine-2H-pyrazolo[
3,4-cl pyrimidine 7 (m, p.

1 09 = 1 10°C), 2.7-di-n-hexyl-4,5,6,7-tetrahydro-5-methyl-4,6-thioxo 2H-pyrazolo[3,4-d)-pyrimicine ( m, p, 96-97℃
), 4.5,6.7-titrahi V rho 2-methyl = 4.6-
Thioxo 7-(5-oxo-n-hexyl)-2H-
Girazolo[3,4-a:]pyrimidine, = 7-allyl-2-n-hexyl-4,5,6゜7-
Chitrahydro 1,5-zomethyl-4,6-thioxo 2H-pyrazolo-[3,4-a]pi1nomicin, 4.5.6.7-Titrahydro 6,5-dimethyl-7
-(2-methylbutyl)-4,6-thioxo 1H-pyrazolo[3,4-d]pyrimidi/, 4, 5, 6 +
' 7-tetrahydro-1,5-zomethyl-7-(2-
methylbutyl)-4,6-dioquine-1H-pyrazolo[
3,4-d]pyrimidine, 7-n-hexyl-4,5,
6,7-tetrahydro-5-methyl-4,6-dioxo-2-n-propyl-2H-pyrazolo[3,4-a:]
Pyrimidine, 4.5.6.7-thitrahigelo 1,5-dimethyl-4
,6-thioxo7-(5-oxo-n-hexyl)-
1H-pyrazolo[3,4-d]pyrimidine, 2-ethyl-7-n-hexyl-4,5,6゜7-titrahyrlow-5-methyl-4,6-thioxo2H-pyrazolo[3,4 -4,1 pyrimicin (m, p, 96-9
7°C), 5-n-hexyl-4,5,6,7-titrahydro 7
-Methyl-4,6-dioxo-1H-pyrazolo[3,4
-a] Pyrimidine (m, p, 138°C), 6-nityl-5-n-hexyl-4,5,6°7-tetrahydro-
1, Fucymethyl-4,6-thioxo 1H-pyrazolo[3,4-d]pyrimidine, 5-n-hexyl-4,5,6,7-thitrahydro3
-(3,4,5-trimethoxyphenyl)-1,7-dimethyl-4,6-thioxo 1H-pyrazolo[3,4-
41pyrimidine, 7-inputyl-4.5.6.7-tetrahydro-5-
Methyl-4,6-thioxo 1H-pilaf c+[3,4
-d] biviricin (m, p, 204°C), 4.5,
6.7-titrahydro-6-(2-hydroxymethyl)
-4,6-Sioquin-5-(3-oxobutyl)-2
H-pyrazolo[3,4-d]pyrimidine, the respiratory promoting extract according to the invention comprises one or more of the blood flow promoting agents mentioned above, if desired in a customary solid or liquid pharmaceutical carrier. It can be conveniently used in pharmaceutical products containing

The extract of the present invention can also be used in combination with calcium antagonists. It has now surprisingly been revealed that the pharmacological action of calcium antagonists can be synergistically increased by the addition of the extracts of the invention.

This can be demonstrated by improved protection against allyl alcohol-induced damage to retinal function.

The retinal damaging effects of allyl alcohol are demonstrated by electroretinography of the eye retina. Electroretinal photographic detection of lesions is described in DocumentaOphth by Gauri et al.
almologica: The Hague, 1
977, P, 335-340 and [Der Aug
enspiegel J No. 9, 1979, P, 1
-16.

To examine the effects of allyl alcohol damage,
Urethane anesthesia was applied to female NMRI mice placed in the dark.
Five minutes before, 100 mg/m of allilucor was administered intraperitoneally. The mice were then subjected to electroretinography (E) within 5 minutes.
RG) fixed to the device.

Furthermore, a silver chloride-glass wool electrode was placed on the corneal surface of the test animal, and a second silver needle electrode was inserted into the spherical diameter of the back of the eyelid of the test animal's eye. ERG-b-wave potential was recorded by total light intensity. By this method, the maximum single-wave potential was confirmed.

To prove the protective effect, test animals were kept in the dark.
The agent solution was first administered intraperitoneally.

After 60 minutes, 100 mg/kli' of allyl alcohol was administered intraperitoneally, and after another 25 minutes, the test animals were anesthetized with urethane, and within 5 minutes they were fixed in the FiRG device as usual.

The results obtained are summarized in the table below.゛Improvement of the protective effect shown by electroretinography in mice against allyl alcohol damage by the combination of an Oa-antagonist and the extract of the present invention.

Control (urethane anesthesia) 1326 Injury with allyl alcohol 665 Nimodepine (A) 9 in 10 m9/oral 707 Bovine blood extract (B) 10 in/! 9. Oral Invention 690
Combination of (A) and (B) Invention 150
3.5/l/thiazem ((:ri 10m9/kg,
Intraperitoneal combination of 585 (B) and (0)
Invention 1177 This result shows that animals treated with the extract of the invention together with an Oa-antagonist are completely protected from damage caused by allyl alcohol, whereas animals treated with the agent alone are only slightly protected. This indicates that only the following are protected.

The extract of the invention has a surprisingly advantageous antiviral effect even without other therapeutic additives. Treatment with this extract is very effective for typical herpes infections (herpes zoster, genital herpes, labial herpes, and corneal herpes). Surprisingly, this effect remains even after oral administration.

The medicament according to the invention can be administered parenterally, preferably in the form of an aqueous solution, with or without solubility aids, or orally in solid or liquid formulations such as tablets, dragees or aqueous solutions.

If desired, they may also be formulated as topical preparations such as ointments, gels, powders or lotions. They can also be formulated as inhalation preparations, eg sprays.

In view of the fact that circulation promoting agents are usually used for long periods of time (often several years), an essential benefit of human therapy is the reduction in toxicity of the compounds with the combination of the present invention.

According to another preferred embodiment, the invention primarily relates to the use of extracts with significant respiratory activity as additives to beer and other alcoholic beverages. Particular preference is given to using the respiratory active extract in an amount of 0.2 to 10% by weight, with respect to the total weight of the respective foodstuffs and indulgences. Particular preference is given to addition in amounts of 0.5 to 7% by weight, especially 1 to 4% by weight.

Foods and luxury goods often contain ingredients that adversely affect normal cellular respiration and metabolism, such as oxidase inhibitors and glycolyse inhibitors. Foods are often sold containing undesirable traces of heavy metal salts and other toxic substances. These substances must be removed from living organisms using active oxygen.

For example, short-term and particularly long-term alcohol cravings result in the formation of aldehyde, especially acetaldehyde,
This becomes harmful to living organisms.

To detoxify aldehyde Ω, living organisms have oxidase, which decomposes aldehyde P using oxygen. By adding respiratory active substances to foodstuffs and luxury goods, detoxification, which is important for living organisms, is achieved.

When the respiratory active extract according to the present invention is used, such living organisms are detoxified. The effects of toxic glycolyse and oxidase inhibitors of toxic substances in food products and luxury goods are prevented or compensated for by application of the present invention.

Substances that alleviate the above-mentioned toxic effects in certain amounts are added to the beer beforehand. The use according to the invention of a respiration-promoting extract as an additive to beer essentially increases the detoxification effect of beer.

The effect of promoting cellular respiration and substance metabolism by using the present invention depends on supporting the energy production process in the living body. By using the present invention, unexpected advantageous nutritional physiological effects of the type described above are obtained.

The following examples serve to further illustrate the invention.

Example 1 Thick blood from a slaughterhouse was separated from plasma and diluted with water to a solids content of approximately 10% by weight. To this blood 101 is added about 10 g of an amylolytic-lipolytic-proteolytic enzyme mixture, for example equal amounts of vancreatin, papain and a mixture of two enzymes obtained by yeast culture. 35-38℃ while stirring evenly and gently.
Heat to. While stirring uniformly at a constant speed, maintain this temperature for about 1 hour, then further heat to about 53-57°C,
Maintain this temperature for about 2 hours, then add the filter aid at the end.
Heat to about 90°C and filter hot through a pressure section machine. The resulting clear filtrate is concentrated in vacuo to about 60% solid and then spray dried. The resulting powder is suspended in a 70/'30 alcohol/water mixture and adjusted to a solids content of approximately 10% by weight. The suspension was allowed to stand for approximately 8-12 hours to allow insoluble matter to precipitate. Filter the clear supernatant liquid and
The alcohol is distilled off and the remainder is spray dried. The product thus obtained is colorless and can be used satisfactorily for the purposes of the present invention. This product can be further purified in order to improve its compatibility with the body. 7
Preferably, a 0/30 alcohol/water mixture is dialyzed against water.

The product purified by dialysis can be used directly for injection and cold immersion.

Example 2 101 defatted fresh carcasses were obtained with 5 g each of pancreatin and papain and fungi and bacteria.
Mix with seed enzyme. Heat to about 36-38° C. and hold at this temperature for about 1 hour while stirring gently at a constant speed. The milk gradually decolorizes and becomes a clear solution. After maintaining the temperature at about 54-56°C and continuing stirring at a constant rate at this temperature, the filter aid is added and heated to about 90°C;
Filter while hot using a pressure filter. The clear filtrate can be filtered using e.g.
and - downflow evaporator (Fallstrom verda)
mpfer) and dried in a spray evaporator. After suspending the product thus obtained in a water-alcohol solution (approximately 80% ethanol/20% water by weight), the suspension is allowed to stand for approximately 12 hours, filtered and the alcohol removed. Evaporate and spray dry the residue again. A colorless product suitable for the purposes of the invention is obtained. For further purification, dialysis against diluted alcohol can be performed.

Example 6'+ 6 kg of skimmed milk powder is dissolved cold in 20 g of deionized water. Stirring for several hours produces a homogeneous solution.

This is further processed as described in Example 2.

A colorless, fully active product is obtained.

Example 4 Placental tissue from a sacrificed animal is ground with a homogenizer and diluted with water to adjust the solids content to approximately 10% by weight. Further processing in a manner similar to that described in Example 1. A colorless, fully active product is obtained.

Example 5 10 kg of wheat sugar is finely ground and suspended in 1 oz of cold distilled water. In this state, the enzyme mixture of Example 1 is added and heated to a maximum of 35° C. with constant stirring.

After keeping this temperature constant for 1 hour, heat to 55-60°C. After stirring again at this temperature for 2 hours, it is heated to 90° C., treated with a filter and clarified with a pressure filter.

The solution was concentrated in vacuo and diluted with an alcohol/water mixture (70
/30) and separated from the precipitated residue. After evaporating the alcohol, the solution is spray dried.

The products according to the invention can be standardized in their biological activity.

Example 6 (Extract from malt) 10 kg of germinated and dried barley was ground to yield 100 A
Suspend in cold distilled water. Heat to a temperature of about 90° C. while stirring at constant speed for 6.5 hours.

Treat with filter aid and clarify using pressure filter. The resulting solution was concentrated in vacuo and mixed with an alcohol/water mixture (70/30
) and separated from the precipitated residue. After distilling off the alcohol, the solution is spray dried.

Example 7 Suspend 1i+ yeast in 100ml of distilled water, disrupt the cells with ultrasound, add the enzyme mixture described in Example 1 while stirring at a constant speed, and slowly reduce the temperature to maximum. 67
℃ and hold at this temperature for about 1 hour. Thereafter, the temperature is raised to about 55-60°C and maintained at this temperature for 2 hours in a conventional manner. After adding the filter voice agent, the mixture was heated to 90°.
C. and treatment of the clear filtrate as described in other examples yields the active product.

Example 8 10 kg of boiled eggs are homogenized in a petri dish, diluted with 100 ml of water, and treated with enzymes at high temperature to yield a clear filtrate. Purify by precipitation with ethanol-water (70:30).

Example 9 10 kg of fresh eggs are treated as described in Example 8 to give the active product.

Example 10 5 kg of potato slag (Petri dish) produced as a waste product from the potato industry was suspended in 507 water.
Mechanically homogenize. After boiling the mixture for 30 minutes,
Cool to 60°C, add enzyme mixture and increase temperature to 67°C.
Make it C. After keeping this temperature for 1 hour, increase the temperature to 60°C.
Hold for 2 hours. Add filter aid and evaporate the mixture. When processed as described above, an active extract is produced.

Application Example 1) Equal i-nocalcium dobesylate and pentoxifylline were dissolved in an aqueous solution of blood extract according to Example 1 at about 0.02 to 0.6%. One dose includes:
Approximately 60 to 100 m9 of dobecilate, 25 to 100
q of pentoxifylline and 1 to 100 m9 of blood extract.

Similar composition formulations can be prepared by mixing the corresponding proportions of solids with conventional pharmaceutically suitable carriers. Similar formulations can be prepared from the blood extract and other blood flow promoting agents described herein, such as vincamine, nicergoline, pyrazolopyrimidines or pyridones described herein. The preparation of the formulations of the present invention requires approximately one-fourth to one-tenth of the usual therapeutic dosage of each agent in combination with the respiratory-promoting natural agents described herein.
use the amount of

2) Injection solution pentoxifylline 40 ■ Blood extract
Add 20 to isotonic saline solution and add 5 m
l! shall be.

3) Cold infusion solution vincamine 800m9 blood extract
Add 6000In910% glucone aqueous solution to make 11.

4) 1000 tablets Pentoxifylline 100.9 Blood Extract
Carrier excipient for 20g tablet
80.95) Anti-blemish Blood Extract Add 5g Improper Tool/Water (60/40) to make 1000d.

Agent Akira Asamura A61K 31/435 6
675-4C31/44 66
75-4 C31/465 6
675-4 C3115056675-4C 311526675-4C 31/626675-4C 31/66 6675-4 C
31/70 6675-4
C priority claim @ October 12, 1982 ■West Germany (
DE)■P 3237838.6 Inventor: Günter Mohler - Dauenhof, Federal Republic of Germany 205 ■Applicant: Günther Mohler - Dauenhof, Federal Republic of Germany 205 Procedural Amendment (0 November 11, 1985 Commissioner of the Patent Office 1. Indication of the case Patent Application No. 190618 filed in 1980. Manufacturing method 3. Person making the amendment Relationship with the case 5. Date of amendment order Month/day 6. number・−7−″)・]

Claims (1)

[Claims] (1) Blood, homogenized cartilage material, skimmed milk, homogenized placenta or muscle tissue, cereal grains, eggs, fish, potatoes, yeast or malt with water added to reduce the solids content to approximately 6 to 14%
Add a lipolytic, amylolytic, and proteolytic enzyme mixture consisting of equal amounts of each of enzymes extracted from animals, plants, fungi, and bacteria, except when using malt, or use plasma directly. , After continuing to stir uniformly for several hours at 3'0-60℃, about 9
Inactivate by heating to 0°C, filter hot, concentrate the filtrate in vacuo, spray dry the concentrate and suspend the powder produced by spray drying in an alcohol/water mixture. After leaving the turbid liquid for several hours, the supernatant liquid was filtered from the solids,
blood, plasma, milk, cartilage material, placenta or muscle tissue, by concentrating or concentrating the filtrate to dryness and, if desired, by dialysis of the product dissolved in a water/alcohol mixture against water; Extracts starting from cereals, potatoes, fish, eggs, microorganisms such as yeast or malt, or extract mixtures consisting of extracts of various of the above starting materials. (2) A mixture consisting of equal amounts of pancreatin, papain, fungal protease and bacterial protease is used as the enzyme mixture. The extract according to claim 1. (3) using about a 70/3 D alcohol/water mixture to suspend the product produced by the first concentration process to a solids content of about 10%. Extract according to scope 1 or 2. (4) Using an 80/20 alcohol/water mixture for the preparation of the extract and resuspending the resulting precipitate in a 70/30 alcohol/water mixture. The extract according to claim 6, which consists of concentrating and drying a cloudy and clear alcoholic solution. (5) At least one of the extracts according to claim 1 to 4. or a pharmaceutical or cosmetic medium containing at least one said extract. (6) At least one extract according to any one of claims 1 to 4. (7) A pharmaceutical medium as claimed in claim 5, comprising at least one vasoactive substance, if desired in a customary pharmaceutically compatible diluent. an extract according to any of the ranges 1 to 4 and at least one of the following agents: a) a vasoactive agent, i.e. +) 2.5-Zohy 1ζ roxybenzenesulfonic acid calcium salt; , also called calcium dobesylate. alkyl (wherein alkyl is the same or different linear or branched straight-chain or branched alkyl residue having from 1 to 4 carbon atoms, and R represents 1 residue -0-OH3 or -c2H2) ) no 6,7-ji hero 6.7-ji 0
1-4-alkyl-(5-substituted)-1H-zo1non? -2,6-Zion, 111) General formula ■ 2 [In the formula, R1 and R2 are the same or different υ, a hydrogen atom or 01-[: i8 alkylkenyl, O, -C8 alkylcarboxylalkyl group] , R1 and R2 cannot be hydrogen atoms at the same time, and A is a group Rδ (wherein R3 represents a hydrogen atom or an alkyl of 01-04, R4 is a hydrogen atom, an alkyl of C□-06 or an alkyl of C2-CG). (representing alkenyl), preferably R1 and R3 are methyl or ethyl, R2 is -(
OH2)4-C! O-C! H3 f] pyrazolo [
6. 4-d] pyrimidine, iV) pyridone of the formula (representing (OH2)2-4′″R), or V) = cervoline, vincamine or dihyridamole, oral) oxygenase inhibitors, i.e. acetylsalicylic acid, fluzenamic acid, (8) Foods Application of the extract according to any one of claims 1 to 4 as an additive to products and luxury goods. (9) Additive to beer beer and other alcoholic beverages, but not yet. Claim 8 as an additive to non-alcoholic beverages, bread, potato products, meat, fish, sausages, fruits and vegetables, or their reprocessed products, dairy products and cheese products, confectionery, and ice cream Application of claim 8 in an amount of from 2 to 10% by weight, preferably from 0.5 to 7% by weight, more preferably from 1 to 4% by weight. or blood, homogenized cartilage, skimmed milk, homogenized placenta or muscle tissue, grain hunting, eggs, fish, potatoes, yeast or malt with water to bring the solids content to about 6 to 14%.
If malt is not used, a mixture of lipolytic, amino acid degrading and proteolytic enzymes consisting of equal amounts of each of enzymes extracted from animals, plants, fungi and bacteria can be prepared. After adding and continuing to stir uniformly at 50-60' for several hours, about 90
Inactivation by heating to After the liquid has been allowed to stand for several hours, the supernatant is filtered off from the solids, the filtrate is concentrated or concentrated to dryness, and if desired the product is dissolved in an alcohol/water mixture, preferably 70/3.
2. The method for producing an extract according to claim 1, characterized in that a solution dissolved in alcohol/water is dialyzed against water.